Tuesday, May 6, 2025

Wernicke’s Encephalopathy in a Bariatric Surgery Patient: A Case Report and Review of the Literature

 

Wernicke’s Encephalopathy in a Bariatric Surgery Patient: A Case Report and Review of the Literature

Introduction

Wernicke’s encephalopathy is an often-unrecognized disease that usually results from chronic alcoholism [1]. Up to 50% of cases could be attributed to either prolonged parenteral nutrition, malignancy, AIDS, chronic malnutrition, or gastrointestinal tract surgery [2]. Because this disease may be less recognized and diagnosed by physicians in non-alcoholic patients, we report this case.

Case Presentation

We present the case of a 14 years old teenager reporting vision and gait disturbances. The patient reported blurred vision and unstable gait, which have started 3 days before presentation. At presentation, the patient was conscious, cooperative, and oriented swaying from side to side upon ambulation. Vital signs were normal with blood pressure 120/75 mmHg, O2 saturation of 98% on room air, a pulse of 86 bpm, and HGT of 105 g/dl. The patient denied any fever, gastrointestinal, respiratory, or urinary symptoms. She denied the occurrence of similar symptoms with any of her close contacts or relatives earlier. She denied any drug abuse and was assured she has had never consumed alcohol. The patient reported having several medical conditions: she has diabetes mellitus, hypothyroidism and has a history of gastric sleeve surgery for morbid obesity since 3 months before admission. The patient is on daily metformin 1000 mg daily and thyroxin 100 mcg daily. The patient reported being on a strict diet and losing about 23 kgs of her body weight since the operation. On the physical exam, she had horizontal diplopia on the vision of objects at short and long distances. The left pupil was non-reactive to light. Bilateral abducens nerve palsy was evident.

Complete oculomotor nerve (CN III) palsy was evident at the left eye while the right eye exam revealed partial oculomotor nerve palsy. The patient was ambulatory with an unstable gait and ataxia. No Babinski sign was evident. The patient had normal motor control of her upper and lower limbs and axial muscles. The examination of sensation was normal. The initial diagnosis was a possible aneurysm or tumor-induced compression of the optic chiasma and oculomotor nerves. ACT angioscan of the brain revealed no tumor, hemorrhage, or ischemia. A cerebral MRI with gadolinium proved normal with no clue of aneurysms, tumor compression, and hemorrhage. An EEG revealed normal brain activity. The patient denied any signs of epileptic seizures and headache. Laboratory workup showed normal complete blood count and differential except for hemoglobin of 11 g/dl and hematocrit of 34 %. Renal and liver function tests were normal. Chest X-ray was normal. Thiamin level was 0.3 ng/ml. The patient was given 1g of thiamin intravenous drip over 2 hours. The patient has been prescribed 100 mg of thiamin intramuscular injections for 2 days with multivitamin B tabs 3 times a day. The patient’s symptoms started to subside by the second day of treatment. The patient was kept on thiamin and multivitamin supplements for ten days. Her symptoms subsided.

Discussion

Thiamin is a cofactor for several enzymes in the Krebs cycle [3]. It is vital for carbohydrate metabolism in the pentose phosphate pathway [3]. A decrease in the activity of these enzymes due to lack of thiamin leads to increased build-up of toxin intermediate metabolites in areas of the brain. This induces damage to the brain and causes Wernicke’s encephalopathy. The acute onset and fast progression of symptoms to coma and death justify the urgency of such condition, and the need for fast diagnosis and treatment [4]. Although Wernicke’s encephalopathy is mainly diagnosed in alcoholic patients, nearly 50% of WE cases occur in non-alcoholics. In addition, to alcohol consumption, malnutrition, gastrointestinal tract surgeries, and malignancies such as acute leukemia, malignant lymphomas, gastric adenocarcinomas, and breast cancer have been associated with WE [5]. The diagnosis of WE is mainly clinical and can be confirmed by laboratory and radiological examinations. Symptoms of WE are mainly neurological and of acute onset. Although only seen in 16% of patients, a triad of gait unsteadiness, ophthalmoplegia, and mental status changes characterizes WE [6].

Mental status changes can range from acute confusion to apathy and inability to concentrate. Progression with no treatment leads to coma and death [6]. A thiamine blood concentration or measurement of the erythrocyte transketolase activity can confirm a presumptive diagnosis of WE [7]. MRI remains the most valuable method to confirm a WE diagnosis [8]. Findings on MRI usually include bilateral and symmetric involvement of Paramedian thalamic nuclei, mammillary bodies, periaqueductal grey matter, and periventricular region of the third ventricle. Most commonly, patients with WE show signal hyperintensities on FLAIR, diffuseweighted and T2-weighted sequences within the posteromedial thalami and surrounding third ventricle [9]. In this case, our patient revealed normal findings on MRI. The diagnosis was mainly clinical with no radiological findings. The immediate response to presumed WE is the parenteral administration of thiamine. Intravenous thiamine of 500mg infused over 30 minutes trice per day for 2 days with vitamin B supplements must be initially given. For additional five days, 500 mg of thiamine must be given intravenously or intramuscularly in combination with a vitamin B supplement [10]. Although rare, WE remains a medical emergency that demands the earliest possible diagnosis and treatment. Clinicians in nonalcoholic patients overlook it, which results in delayed treatment and symptoms’ progression into coma and death. The prognosis of WE with early diagnosis is favorable, as shown in this case where complete remission was attained with early treatment.

Summary of the Case

(Table 1).

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Table 1.

Consent

The patient has signed a clear consent allowing the usage of the data related to her condition and the publication of this case report.


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A Versatile Integrated Digital Prosthetic Workflow for the Immediate Pink-free Full-arch Restoration: A Case Series

 

A Versatile Integrated Digital Prosthetic Workflow for the Immediate Pink-free Full-arch Restoration: A Case Series

Introduction

Implant-fixed complete dentures (IFCDs) are well established for the immediate rehabilitation of edentulous patients [1]. Selecting an adequate treatment scheme represents one of the most important factors for the long-term clinical success of IFCDs [2]. This selection requires considering a wide range of objective clinical parameters, including anatomic, medical, technical, mechanical, and biological characteristics [2-4]. In addition, subjective patientperceived outcomes, including preferences and satisfaction, have recently gained equal importance in evaluating final treatment outcomes [5-7]. Depending on the interarch space and the dentogingival transition line, the overall prosthetic design of IFCDs has been traditionally broadly classified into crown-only white bridges or white–pink hybrid prostheses consisting of crowns and pink gingiva [8]. While this classification has proven useful to provide general guidance regarding prosthetic design and esthetics, more specific design guidelines and evaluation criteria for the aesthetic outcomes of IFCD treatments, remain pending [3]. The digitalization of prosthetic workflows and the introduction of new materials, e.g., full-contour monolithic zirconia (FCZ), have recently triggered a substantial transformation of prosthetic design approaches [3,9]. Digital smile design allows, e.g., to visualize the prosthetic design of IFCDs in context to the patient’s smile symmetry and modify and validate its esthetic aspects online and in real-time based on direct patient input [10,11]. Furthermore, techniques have emerged that allow adapting the cervical aspects of IFCDs with a high level of detail to the local soft and hard tissue anatomic preconditions.

Such approaches have been shown to deliver IFCDs with natural, teeth-like, and individually adapted designs [12,13]. In the absence of remaining dentition, these techniques can be used to fully redesign complete dental arches according to well-established functional and aesthetic design principles [10,14]. All of this may render the design approaches towards full-arch prosthesis more flexible and patient-centered when compared to the traditional approaches. In a recent publication by this group, an advanced digital workflow for accurate and efficient immediate full-arch restoration with an aesthetically and anatomically adapted natural tooth-like prosthesis has been presented [14]. This manuscript illustrates the application of this workflow to a range of anatomic conditions and indications. Specifically, its application in patients displaying varying levels of alveolar atrophy and with various dental restorative preconditions will be presented.

Materials and Methods

This case report describes the application of an integrated prosthetic workflow for the rehabilitation of four adult patients. All patients consented to IFCD treatment. None of the patients displayed any medical or psychological condition contributory to implant treatment. All patients displayed varying levels of remaining maxillary dentition indicated for extraction. Treatments were provided in a private clinic center (Sobczak Clinical Centre, Radosc, Poland) using the advanced, fully digital restorative protocol (Sobczak Concept®) illustrated in Figure 1. The detailed implant restorations were planned based on CBCTs scans (HyperionX9, MyRay, Imola, Italy) and diagnostic wax-ups (Implant studio, 3Shape A/S, Copenhagen, Denmark). The latter were derived from pre-treatment IOSs (3Shape TRIOS®, 3Shape A/S, København, Denmark) in close bite comprising the maxilla-mandibular relation (Figures 1a & 1b). The coronal and esthetic aspects of the diagnostic wax-ups were optimized based on frontal photographs using digital smile design (DSD) (in-CAD Smile Creator, exocad GmbH, Darmstadt, Germany). They were further used to examine the maxilla-mandibular relation and diagnose any required general or local soft or hard tissue augmentative or resective procedures. The prosthetic models were refined and finalized chair-side postimplant placement by using intra-surgical intraoral scans after mounting screw-retained abutments (SRAs) (titanium abutments, Institut Straumann AG, Basel, Switzerland) and scan bodies (CARES®, Institut Straumann AG, Basel, Switzerland). Residual dentition was strategically temporarily left in situ (Figures 1c & 1d) to facilitate the registration of individual IOSs and establish a geometric relationship between the diagnostic and final wax-ups (Exocad, DentalCAD, exocad GmbH, Darmstadt, Germany). The latter were finalized by adapting the soft-tissue interfacing cervical aspects of the prosthetic framework considering actual implant positions and the resulting post-placement soft-tissue contours and thickness [15]. Provisional restorations were chair-side printed and delivered on the day of implant placement (CARES® C Series, Institut Straumann AG, Basel, Switzerland). Final in-house milled (Ceramill®, motion2, Amann Girbach AG, Rankweil, Austria) multilayer zirconia bridges (IPS e.max ZirCAD Prime, Ivoclar Vivadent AG, Lichtenstein) were delivered at 6 months post-surgery.

Results

Case 1

Case 1 illustrates the treatment of a young, 41-year-old male patient with failing maxillary dentition and malocclusion, who presented in our clinic with a chief complaint of poor aesthetics, pain, and progressive deterioration of masticatory function. Intraoral examination revealed multiple failing maxillary teeth affected by carious decay down to the root and pulpitis. CBCT scans indicated adequate overall bone quantity. As illustrated in Figure 1a, the patient displayed a lateral canine guidance-related malocclusion. Under consideration of the young age of the patient and expected elevated masticatory forces, a first-molar-to-first molar restoration supported by 8 implants was defined [16,17]. BLT (Positions 12, 15, 21, and 24) were combined with BLX implants (Positions 14, 17, 22, and 27) (Institute Straumann AG, Switzerland) for optimal immediate stability [18,19]. Implant lengths and implant diameters ranged from Ø3.3 x 12mm in anterior positions to Ø4.5 x 8mm in posterior positions and were defined based on locally available bone volumes. Figure 1C shows the clinical situation after tooth extraction and immediate implant placement with cuspids still left in situ to register individual scan and waxing model data sets [20,21]. Figure 1e illustrates the restored maxilla-mandibular relation and raised occlusal vertical dimensions after immediate provisionalization [12].

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Note: DSD: digital smile design, CBCT: cone-beam computer tomography, IOS: intraoral scan.

Figure 1: Treatment scheme comprising the applied surgical and prosthetic steps. Individual steps of the prosthetic procedure are illustrated in green, and surgical steps are illustrated in grey. Pictures illustrate the individual prosthetic data sets, including

a) a: Pre-treatment IOS in close bite,

b) b: Diagnostic wax-up in relation to the planned implant restoration,

c) c, d: IOS#1 and IOS#2 after placement of implants, SRAs and scan bodies before and after strategic extraction of remaining teeth, respectively. These remaining teeth were used to register pre-treatment IOS, IOS#1, and IOS#2 and were used as landmarks to match diagnostic wax-ups and the actual implant restoration.

d) e: Final wax-up after chair-side adaption of the cervical contours of the prosthetic framework to the resulting postplacement soft-tissue contours.

e) f: IOS in close bite 1 week after delivery of the immediate provisional restoration.

Case 2

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Figure 2: Case 1: Immediate maxillary full-arch restoration in a young patient with failing maxillary dentition and malocclusion.

a) Frontal photograph illustrating the esthetic situation and lip line prior to treatment,

b) Clinical intraoral situation of the patient without conventional partial denture prior to treatment.

c) Occlusal view after implant placement and restoration with screw-retained abutments (SRAs) and scan bodies. Canines were temporarily left in situ as landmarks to match individual intraoral scans

d) Frontal photographs after immediate delivery of the provisional restoration.

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Figure 3: Case 2: Immediate full-arch restoration of a patient presenting posterior bone atrophy and antero-vestibular bone deficiency.

a) a: Retracted frontal view illustrating the situation with conventional removable partial prosthesis prior to treatment.

b) b: Occlusal view on remaining dentition and atrophied distal alveolar crest.

c) c,d: Occlusal and frontal view planned implant positions.

d) e: Clinical situation at IOS#1, i.e., after implant placement, local bone augmentation in zone 11, and SRAs and scan bodies placement. Teeth 21 and 23 were temporarily left in situ.

e) f: Frontal view 1 week after immediate provisionalization illustrating the overall anatomically and aesthetically driven restorative concept.

Case 2 describes the treatment of a 53-year-old female with a moderately atrophied posterior maxilla and a local bucco-anterior bone deficiency. The patient presented with a chief complaint of poor aesthetics and fit of her upper conventional partial denture (Figure 2a). Dental examination and diagnostic CBCT revealed residual dentition in positions 21 to 23, a moderately atrophied posterior edentulous alveolar ridge, and a buccal bone deficiency in the anterior zone (position 11) (Figures 2b & 2d). The aesthetic evaluation indicated a regular smile line at the dento-gingival margin. A first-molar-to-first-molar restoration supported by 6 BLT implants (Institut Straumann AG, Switzerland) was planned (Ø3.3 mm, L:10, and 12 mm; positions 12, 14, 16, 22, 24, and 26). Distal implants were placed slightly medially to compensate for the posterior atrophy. Anterior implants were angulated to ensure adequate engagement with the cortical bone for optimum primary stability. Horizontal bone augmentation using Xenograft and a Collagen membrane (Cerabone/Collprotect, Institut Straumann AG, Switzerland) was performed to compensate for the anterovestibular bone deficiency [22,23]. Figure 2e illustrates the clinical situation after implant placement, bone augmentation, and placement of scan bodies with teeth 21 and 23 left temporarily in situ as landmarks for individual intraoral scan data registration [11]. The comparison of pre-and 1-week post-treatment situations in Figures 3a and f illustrates the applied changes and adaptions in teeth shape and form to the local soft and hard tissue anatomy. Specifically, teeth in the anterior and posterior positions were slightly prolonged to improve the soft tissue adaptation and compensate for the moderate posterior atrophy without disrupting the patient’s overall tooth phenotype.

Case 3

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Figure 4: Case 3: Immediate full-arch restoration of a patient with a distally atrophied maxilla.

a) Aesthetic assessment indicating a low smile line below the dento-gingival margin.

b) Frontal view of the maxilla presenting 2 residual canines, signs of local denture-induced hyperplasia in the frontal alveolar aspect, and distal maxillary atrophy.

c) Prosthetic and surgical restorative plans of a first-molar-to-first-molar prosthetic framework supported by 6 implants in occlusal view.

d) Overlayed visualization of pre-and post-implant placement IOS and IOS#1 visualizing possible soft tissue anatomic contour changes for the cervical prosthetic contour planning.

e) Occlusal view after implant placement. Soft tissue incision between the distal implants and release of a mucoperiosteal flap before contour augmentation.

f) Frontal view of the patient 1-week post-treatment illustrating the improved smile and incisal lines providing the patient with a subjective younger smile typology.

Case 3 illustrates the treatment of a 61-year old female patient (64 years old) with local posterior maxillary atrophy. The patient addressed herself to the clinic, requesting a more permanent, natural teeth-like restoration without palatal coverage and with improved hold. As evidenced in Figure 3a, the patient presented a low smile line covering the dento-gingival margin. Oral examination indicated local signs of gingival denture-induced hyperplasia (Figure 4b). Osseous alveolar dimensions in the frontal aspects were adequate. However, distal aspects of her alveolar ridge were moderately atrophied with a sharp knife-edged morphology. Based on provisional wax-ups and virtual planning models, a first-molarto- first molar restoration on 6 implants in positions 12, 14, 16, 22, 24, and 26 was planned (Figure 4c). The implant restoration was based on 4 anterior BLT implants (Ø 3.3mm x 12mm) and 2 posterior short implants (position 16: BLT, Ø4.1x8mm; position 26:BLX, 3.75x6mm), avoiding prosthetic cantilevers [24-26]. Horizontal alveolar contours between the distal implants were bilaterally augmented to compensate for missing tissue support using Xenograft combined with a Collagen membrane (Cerabone/ Collprotect, Straumann, Switzerland) (Figure 4d). Overlays of preand immediate post-operative IOSs were used to identify changes in the overall soft-tissue anatomy to design the cervical prosthetic contours. Figure 4f shows the patient’s smile appearance 1 week after immediate provisionalization. The comparison between preand post-treatment photographs in Figures 4a & 4f illustrates the patient’s aesthetic smile line changes. Specifically, upper crowns were slightly lengthened, and lip support was increased. These modifications improved the ratio between revealed upper and lower crowns, which resulted in a typologically younger aesthetic smile phenotype.

Case 4

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Figure 5: Case 4: Transitioning a failing conventional restoration into a fixed immediate full arch implant restoration.

a) Failing conventional restoration prior to treatment.

b) Digital wax-up of the planned restoration.

c) Frontal view after conventional restoration removal and abutment incisor fracture.

d) Frontal view after placement of surgical guide and

e) After placement of implants and restoration with scan abutments.

f) Frontal view after immediate provisionalization.

Case 4 illustrates the immediate transition of a failing conventional tooth-borne restoration into an IFCD. The patient, a 56-year-old female, was referred with a complaint of pain and increasing mobility of her restoration. Zones around abutment teeth 21 and 15 displayed acute inflammation and suppuration (Figure 5a). The existing restoration’s maxillomandibular relationship, OVD, and aesthetic aspects were evaluated as optimal. The design of the existing restoration was directly replicated in the fixed restoration after minimal adjustments to the emergence and angulation of the cuspid crowns (Figure 5b). The patient displayed adequate alveolar dimension to support a first-molar-to-firstmolar restoration on 4 straight anterior and 2 17°-tilted posterior implants (BLT, Ø3.3x12mm, Institut Straumann AG, Switzerland). Surgical guide placement was adversely affected by the fracture of the central incisor in position 11 upon removal of the existing restoration. This unforeseen event reduced the retention to two anchoring pins (Figure 5d). As indirectly verified by IOS#1 after removing tooth remnants, placing implants, and installing scan bodies, its positioning was not significantly compromised (Figure 5e). In this case, palatal rugae and posterior maxillary tuberosities were used as landmarks for the registration of individual IOSs. The resulting final wax-up was obtained by adjusting the cervical contours and connecting geometries of the prosthetic framework to the resulting soft-tissue anatomy and actual implant positions. This chair-side prosthetic planning allowed to efficiently transition the failing conventional restoration into an immediate implantborn fixed restoration with immediate passive fit despite the experienced intra-surgical complications.

Discussion

The presented clinical cases illustrate the capabilities of modern advanced digital workflows to accurately, efficiently, and robustly deliver aesthetically and anatomically adapted IFCDs in a wide range of indications [9]. The applied digital workflow has been recently described for the treatment of fully edentulous cases [14]. One of the most important features of the presented workflow is its capability to individualize the prosthetic framework to the patient’s micro-and macro-aesthetic appearance and local soft and hard tissue anatomic preconditions. This important capability is based on combining multiple individually described prosthetic techniques and directly integrating the resulting prosthetic procedures into the surgical workflow. The advantages of designing the visible coronal aspects of immediate IFCDs from a facial and aesthetic perspective have been brilliantly illustrated, e.g., by Coachman et al. [11]. The micro-and macro-aesthetic principles for defining teeth sizes, shapes, and positions and the overall form of the dental arch in relation to smile lines and face symmetries have been well established and represent the basis of digital smile design (DSD) [10,27].

One of the major advantages of modern DSD routines, when applied as part of IFCD treatments, is the possibility to redesign dental arches according to these principles fully. Virtualization further allows to directly visualize and modify the aesthetic concepts in real-time and in close cooperation with the patient himself. This direct patient feedback as part of DSD is routinely implemented as part of our procedures and approximately XY % of patients make active use of this possibility In addition, the immediate provisional itself was also actively exploited for patient feedback, and its transition into the final restoration was actively used to potentially adapt the aesthetic appearance of the prosthetic design for the final restoration. Despite this intrinsic possibility for aesthetic design changes, the evaluation of over 350 patient records indicated that 97% of treated patients in our clinics actively consented to directly transfer and replicate the aesthetic aspects of the provisional into the final restoration with little or no modification. With regards to adapting the cervical aspects of the prosthetic framework to the local soft and hard-tissue anatomy, Pozzi et al. and Salama et al. have presented digital techniques to plan and adapt soft and hard-tissue anatomical crestal contours to ideally support an anatomically designed pink free implant born restoration (FP-1 and FP-2) [13,15]. This approach was modified as part of our workflow by planning and modifying the cervical aspects of the prosthetic framework to the resulting post-placement 3D anatomical hardand soft tissue contours and implant positions. Specifically, the prosthetic contours of the prosthetic wax-up were planned for direct and tight soft tissue contact. Soft tissue thicknesses between the prosthetic contour and the underlying alveolar bone were planned at≥3 mm to prevent any soft tissue complications [15].

As further illustrated by case descriptions 2 and 3, local bone grafting was performed to improve the prosthetic framework tissue support. The requirement for such procedures was identified at the diagnostic wax-up stage and included in the surgical plans. Likewise, whenever possible soft tissue architectures were kept intact to facilitate the cervical prosthetic planning using guided, preferably flapless implant placement. Ideal planning of regenerative procedures and cervical soft tissue contours at the stage of the diagnostic waxing process also consistently considered post-extraction physiological alterations of the soft and hardtissue contours. The general typology of such changes and the factors influencing them, e.g., the crestal bone wall and soft tissue phenotypes, have been previously described [28,29]. To our knowledge, this is the first report that describes the combination of pre-treatment DSD and anatomically driven post-placement prosthetic contouring to IFCD treatments as part of a fully digital workflow. Regarding overall prosthetic design, it also needs to be acknowledged that the presented cases were classified as teethonly defects that allowed for a design of a white bridge (FP-1 and FP-2) [8]. However, the capability of advanced virtual prosthetic planning models as presented herein and its capability to fully redesign dental arches according to well-established functional and aesthetic design principles may also allow the delivery of white bridges to indications traditionally regarded as combined defects requiring pink esthetics (FP-3) [10].

Accurate scanning and an error-free combination of multiple direct digital full-arch scans were pivotal for the accurate planning of the final wax-up [9,30]. These scans spanned the entire arch and were required to derive a waxing model with accurate information on the soft tissue contour and actual implant positions. The anatomical characteristics of partially edentulous arches and the intrinsically associated relatively low number and relative distance between characteristic anatomic landmarks rendered the registration of individual pre- and post-placement scans and the diagnostic wax-up demanding [30]. In the presented procedures existing dentition was systematically left temporarily in situ as part of a strategic extraction protocol to overcome these limitations and provide distinct landmarks for scan alignment [20]. Further, Palatine rugae and tuberosities were also consistently used to ensure adequate scan alignment and verify individual scan accuracy. At the same time, precautions were taken to limit the impact of any factors affecting scan accuracies like tongue movement or the limited space in the distal scanning regions [9]. Another important feature of the workflow was the combination of pre-placement surgical planning and integrated post-placement verification of implant positions at the diagnostic and final wax-ups stages, respectively [21,31]. This feature rendered the immediate prosthetic fit accurate and the workflow robust towards intra-surgical adverse events. Due to the limited capability of CBCT scans to deliver quantitative bone density information, implant positions were mainly planned based on bone volume [32]. Primary stability was always simultaneously verified using insertion torque values. Further, the implant type was flexibly varied, between classical tapered bone level (BLT) implants for regular osseous conditions and novel BLX implants for immediate placement and in conditions with poor bone quality. This latter implant type displays a more pronounced protruding thread geometry for increased engagement with low-density bone [19]. To our knowledge, this is the first report illustrating the combined use and variation of implant types to maximize the primary stability of IFCD treatments. Finally, workflow robustness may be considered another important factor, specifically when considering the complex nature of IFCD treatments. Tahmaseb et al. reported that the rate of intraoperative and prosthetic complications of digital surgical procedures might reach 36.4% [33]. Although this relatively high rate seemed to be closely related to the technology learning curve, the successful and accurate restoration of patient 4 illustrates how the presented workflow may help mitigate even pronounced intrasurgical complications [34].

Conclusion

Advanced integrated prosthetic workflows based on pre-and post-placement direct digital impressions represent a powerful methodology to robustly deliver immediate chairside manufactured with optimal immediate passive fit in a wide range of indications. The combination of digital smile and anatomically driven cervical prosthetic design provides access to patient-centered, aesthetically optimized, natural pink-free restorative designs that may have been classically regarded as combined defects requiring pink esthetics.


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Wednesday, April 30, 2025

Research and Comparison on Modification of Medical Polylactic Acid

 

Research and Comparison on Modification of Medical Polylactic Acid

Short Communication

PLA which is widely used in orthopedic implants, drug carriers, and medical films, can be degraded into harmless lactic acid. There are two main methods for the synthesis of PLA: direct polycondensation of lactic acid and ring-opening polymerization of lactide [1]. When lactic acid is directly polycondensed, high molecular weight PLA cannot be obtained due to the production of water. High molecular weight PLA is usually prepared by the ringopening polymerization process of lactide. There are two main ways of PLA in vivo: hydrolysis and enzymatic degradation [2]. In the actual process, the two degradation modes work together, and which mode is dominant is closely related to the internal structure of the material, hydrophilicity, and molecular weight.

PLA Synthesis Method

There are three ways to synthesize PLA, direct polycondensation of lactic acid monomer, ring-opening polymerization of propylene glycol ester and further polymerization of lactic acid prepolymer. The first method is to directly obtain the polymer by the bulk condensation polymerization of lactic acid monomer. This method is simple to operate, low in cost and high in purity, but it is not easy to obtain high molecular weight PLA. The second method which most literatures use to prepare PLA [3], can obtain high molecular weight PLA. Depending on the catalyst, it can usually be divided into anionic ring-opening polymerization, cationic ring-opening polymerization and coordination. Ring-opening polymerization. The third method is to first heat the lactic acid monomer to prepare a prepolymer, then add a catalyst to the system and remove the water generated by the reaction.

Toughening and Modification of PLA

Block Toughening

Block copolymers are generally soft and hard segments connected polymers with good toughness and elasticity. The introduction of polymer segments with low glass transition temperature into the main chain of PLA has obvious toughening effect. Polytrimethylene carbonate and polycaprolactone have good biological activity, can be degraded non-toxic in vivo. At the same time, the monomer can be directly ring-opening polymerization with lactide, which is a biodegradable product. Excellent choice for polymer materials.

Graft Toughening

Graft toughening is generally based on rubber as the main chain, PLA segment as the side chain or direct synthesis of branched PLA. Inside the polymer, the PLA side chains are entangled with each other, which increases the stress transfer and realizes the toughening of the material. The PLA grafting reaction can initiate the polymerization of lactide through macroinitiators to form dendritic polymers to increase the toughness of PLA [4], such as polyisoprene.

Co-Blended Toughening

Co-blended is a method in which two or more polymers are uniformly mixed in a certain way (solution, melt or mixing) to improve material properties. Compared with the copolymerization method, the Co-blended method is simple, low in cost and widely used in industry. Polycaprolactone degradation products are nontoxic, have good biocompatibility, and have high elongation at break, making it the best choice for the toughening phase of biomedical PLA [5].

Plasticizing and Toughening

Plasticizers have good compatibility and can reduce the glass transition temperature of materials, improve the flexibility of glassy polymers, and play a role in toughening and plasticizing [6]. Polyethylene glycol has good biocompatibility, is degradable in vivo and the degradation products are non-toxic. Adding it to PLA can improve the crystallization speed of PLA.

Composite Toughening

In order to improve the mechanical properties of PLA and obtain strong PLA, inorganic nanoparticles can be introduced into the system to form a ternary composite toughened system. Montmorillonite, tricalcium phosphate and hydroxyapatite have been used [7]. It is proved that it can promote the mechanical properties of the material.

Comparison of Different Toughening Methods

The Co-blended toughening is simpler than block toughening and graft toughening, and is easier to use in industry, but it does not significantly improve the thermomechanical properties of PLA. The block toughening has obvious toughening effect on the material, and due to the chemical bonding between the molecular chains, the thermomechanical properties of the polymer change significantly. The above toughening methods are often accompanied by a decrease in mechanical strength. The introduction of nanoparticles can alleviate this situation, but some nanoparticles have poor dispersion, which has a negative impact on the mechanical properties of the material. The above-mentioned toughening methods have advantages and disadvantages and can be selected according to the application requirements. Biomedical materials have high requirements on the controllability of their components, structures, and properties. To achieve the controllable construction of biomedical PLA systems, it is necessary to select appropriate methods for different application scenarios.


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Qubits- Towards a Better Understanding of the Microzymas

 

Qubits- Towards a Better Understanding of the Microzymas

Short Communication

Large molecules are far too complex for modern computers to calculate what happens to them during a reaction, but the power of quantum computers could open the doors to further understanding these molecules” [1]. Computing and the computer was hardly in existence or at best in in its infancy (if not in an embryonic stage) when Professor Pierre Antoine Bechamp (died 1908) discovered the microzymas in the 1850s. Whoever will make the next breakthrough in our understanding of the microzymas/cellular dust will have to do a lot of work with computers. Quantum computers to be precise [2-3]. What we have to understand is how and why microzymas coordinate, decoordinate and morph. The similarities between qubits and cellular dust is uncanny as a model thereby [4-5].

Consider the following for this model

1. Let a cell represent a bit and a microzyme a qubit.

2. Microzymas morph into germs.

3. Let zero [0] represent the microzymas and the numeral one [1] represent a germ.

4. Qubit behavior of superposition vis a vis the conventional binary mode of bits mirrors the morphing/pleomorphism of cellular dust to germs and vice versa.

5. Understanding the transitory “flux” state of fluctuation and flexibility during morphing could be realized via quantum computing modelling. In short what microzymas do is a sort of biological quantum entanglement.

6. Also to be utilized are Ramanujan’s summation and string theory.


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Monday, April 28, 2025

The Role of Bentonite Clays in Aflatoxin- Decontamination, Assimilation and Metabolism in Commercial Poultry

 

The Role of Bentonite Clays in Aflatoxin- Decontamination, Assimilation and Metabolism in Commercial Poultry

Introduction

Defined as secondary toxic fungal metabolites, mycotoxins are the greatest feed safety concerns in tropical regions [1]. They are also the most potent natural carcinogens linked to severe illnesses and an increase in the risk of liver cancer in humans as well as performance decline in commercial poultry [2]. Nonetheless, several agricultural products used for poultry feed formulation are highly susceptible to mycotoxin contamination under humid conditions. As a result, these toxins are more prevalent in tropical areas where humid environmental conditions favor fungal growth and mycotoxin production [2]. For that reason, many countries and multilateral agencies have established regulations to protect humans and poultry from consuming such contaminated products [3]. On the contrary, many underdeveloped countries like Uganda have no regulations on poultry feed safety, leaving farmers with the burden of battling the mycotoxin-associated production constraints.

Among the numerous mycotoxins, aflatoxins (AF) are the most predominant toxins hence largely contributing to the pool of toxins in the poultry feeds [4,5]. These toxins are produced by Aspergillus flavus and Aspergillus parasiticus which are common contaminants in cereal grains, oilseeds, nuts, and animal-based feed formulation ingredients [6,5]. Since these are the key feed formulation ingredients, the risks of aflatoxin toxicity are high in intensive poultry production systems. However, defined as clinical defects associated with aflatoxin ingestion, aflatoxicosis is associated with increased susceptibility to microbial stress, reduction in immune function, feed utilization, egg-laying percentage, and organ health in poultry [6,7]. Since most of the poultry feeds in Uganda are heavily contaminated with aflatoxins [8], a grave threat to commercial poultry production resulting from reduced vaccine efficacy, organ health, and feed conversion efficiency is inevitable [6,9].

On the other hand, there is no practically effective means of decontaminating feeds by destroying aflatoxins without compromising their nutritional quality [9]. This implies that the utilization of chemically inert aflatoxin sequestering agents like bentonite clays and activated carbon needs to be prioritized. However, the choice of any binder is greatly dependent on its availability and the economic feasibility of its utilization. Among the substances investigated as potential aflatoxin-binding agents, bentonites clays and activated charcoal have proved to be the most promising [10]. However, the cost-effectiveness of activated charcoal has been so variable [11], while different bentonite clays have yielded consistently promising results [6]. Recognized for forming stable complexes with aflatoxins, bentonites clays have strong affinities for aflatoxin sequestration in the gastrointestinal tract (GIT) [12]. Such sequestration is achieved through bentonite clay hydration in which the polar water molecules weaken the interaction between the closely packed bentonite layers for aflatoxin molecule intercalation [13,14]. Consequently, the resultant complex can be eliminated in the fecal materials hence preventing aflatoxin absorption into the bloodstream [15-17]. Therefore, among the several aflatoxin decontaminations approaches, bentonite clay utilization is envisaged to offer the most reliable responses.

Discussion

The Aflatoxicosis Feed Problem

Most of the poultry feeds in Uganda are highly contaminated with aflatoxins (65-1000 ppb) far beyond the acceptable limits of 20 ppb [18]. Due to the dependence on such feeds, commercial poultry in Uganda is highly susceptible to aflatoxicosis, which is reflected in the reduced growth and health performance [9,19]. As a result, severe losses due to poor poultry productive performance and health defects are common due to the consumption of aflatoxin-contaminated feeds [20,21]. On the other hand, commercial aflatoxin decontaminants are not readily accessible which culminates in both technological and logistical challenges. Nonetheless, Phillips et al. and Hesham et al. studied the utilization of dissimilar bentonites in broilers and recommended contradictory inclusion levels of 0.5% and 1.0%, respectively [22,23]. In addition, bentonites are very specific in toxin adsorption, yet they also exhibit great diversities in nature [24,25]. This implies that, any attempts to improve poultry performance through bentonite clay-based aflatoxin-decontamination yield inconsistent results for different bentonite clay deposits. Such inconsistencies are attributed to the highly variable location-specific physiochemical properties among the bentonite’s clays hence the need for location-specific optimum inclusion level determination [25].

Furthermore, comparable studies on other bentonites clays have been conducted, while none has been done particularly on the Albertine bentonite clays. Besides, these studies also do not highlight responses of broiler and layer chickens with respect to aflatoxin carry-over, relative organ health, blood antibody titers alongside egg production indices. In addition, no studies have compared the performance of commercially available aflatoxin binders with the Albertine bentonite clays. Therefore, due to the inconsistent and insufficient information regarding the optimum bentonite clay inclusion levels in poultry feeds coupled with a dearth of information on the Albertine bentonites clays as aflatoxin binders [9], a study to assess the effect of adding these clays and commercial binders as aflatoxin decontaminants was necessary.

The Decontamination Potential of Bentonite Clays

The consumption of aflatoxin-contaminated feeds poses vast aflatoxicosis-related production deficits as well as contamination of poultry products [26]. The resultant aflatoxicosis, which is associated with compromised feed conversion efficiency, reduced vaccine efficacy, and histological organ deterioration, becomes a key production challenge [7,6]. Such challenges not only increase the cost of production but also the risk of losing birds due to highly infectious diseases like Newcastle and infectious bursal disease, which are known to cause up to 100% chicken mortality [26,27]. For that reason, poultry productivity cannot be improved without embracing aflatoxin-decontamination technologies from the feeds. Whereas research has shown that aflatoxin decontamination improves commercial poultry performance [26] the spectrum of decontamination techniques is limited to chemically inert bentonite clay binders and activated carbon. However, the costs involved in the production of activated carbon are prohibitive which results in its scarcity while bentonite clays are readily available as waste in oil extraction [9]. Fortunately, Uganda is endowed with huge deposits of bentonite clays in the Albertine graben region. Elsewhere, these bentonite clays have been reported to have aflatoxin sequestration abilities but with noticeable variations due to physiochemical diversity [28,22,25]. In addition, there is also a scarcity of literature regarding the optimum inclusion levels of the different Albertine bentonite clays as well as their comparative performance with respect to the commercial binders in poultry feeds. Consequently, despite the availability of such bentonite clays, farmers still make huge aflatoxicosis-induced losses due to poor feed utilization, reduced vaccine potency, and hence high mortalities. Therefore, the use of the Albertine bentonite clays as aflatoxin- binders would be a more sustainable decontamination method of averting aflatoxicosis to offset the heavy poultry production losses and the carcinogenic consequences of consuming contaminated poultry products.

Occurrence of Mycotoxins in Foods

Defined as secondary toxic metabolites of Aspergillus species, mycotoxins can be produced on a variety of products from plant and animal origins containing more than 95% water activity [29,30]. The term mycotoxin comes from the Greek word ‘mykes’ meaning mold, and ‘toxicum’ meaning poison that causes a clinical condition referred to as mycotoxicosis [30,31]. Besides, mycotoxins are also reported to be harmful to both humans and animals when absorbed either through ingestion, inhalation, or dermal absorption [4]. However, it was later discovered that ingestion through contaminated foods is the main source of exposure to both humans and livestock [29]. This implies that; besides the direct consumption of contaminated products, humans can also get intoxicated during livestock feed preparation [4]. Recognized for their toxicity, mycotoxins have been reported to be more serious in tropical humid regions where climatic conditions favor the growth of Aspergillus species [32,18]. Such humid conditions, poor postharvest handling, and poor storage facilities make poultry feeds highly susceptible to fungal contamination [32]. Consequently, most poultry feeds in Uganda are found to be highly contaminated with aflatoxins ranging between 65 and 1000 ppb [18]. However, such contamination levels are far beyond the limit of 20 ppb beyond which feeds become unsafe for consumption [33]. Among the many mycotoxins discovered, aflatoxins are the most toxic and highly carcinogenic metabolites of Aspergillus species [4]. Moreover, these toxins which also naturally occur in combination are identified as class one human hepatocellular carcinogens [34]. In addition, aflatoxins B1 can also be metabolized in animal tissues to aflatoxin M1 from bio-activation pathways and excreted in milk [35] hence propagating the effects to infants and higher in the food chain.

Occurrence of Aflatoxins in Livestock Feeds

Aflatoxins were first isolated and characterized from Aspergillus species in poorly stored grains [36]. They were later identified to be associated with the killing of young turkeys in England and ducklings in Kenya as well as Uganda [36,29]. Therefore, these outbreaks gave way to a multitude of discoveries in determining the different types of aflatoxins alongside the associated clinical signs [37]. In addition, these toxins were discovered to be hepatotoxic with their susceptibility being dependent on species, age, nutritional status, and duration of exposure [38]. Currently, aflatoxins are known to be mainly produced by Aspergillus flavus, Aspergillus parasiticus, Aspergillus nomius which use livestock feeds as substrates [39]. Whereas 20 aflatoxins have been identified, only four (B1, B2, G1, and G2) have been widely studied due to their magnitudes of toxicity [40]. Among the four, aflatoxin B1 is the most common and dangerous to both humans and livestock [3]. However, aflatoxins naturally exist in combinations implying that focus has to be put on their synergistic effects rather than the individual effects [41]. Aflatoxins B1, B2, G1, and G2 are widely studied due to their high prevalence in food products and toxic effects [42,30]. Identified to be metabolites of aflatoxin B1 and B2, respectively, aflatoxins M1 and M2 occur in both milk and eggs of species fed aflatoxincontaminated diets [41] Besides the active aflatoxins, significant quantities of conjugated aflatoxins have also been reported to exist in feeds as well [43]. Such conjugated aflatoxins can cause unexpected toxicity when they are hydrolyzed to the precursor toxins in the gastrointestinal tract (GIT) [43]. Furthermore, as part of plant metabolism, some aflatoxins can be transformed into conjugated forms presenting additional forms of toxicity [44]. For instance, zearalenone-4-beta-d- glucopyranoside, zearalenone and deoxynivalenol glucosides which are precursors can be metabolized to the respective active toxins in the GIT [45,46]. Unfortunately, these precursors cannot be detected during routine analysis, yet they can hydrolyze during digestion contributing to the toxin pool in the GIT [45].

Perseverance of Aflatoxicosis

More than ten thousand million metric tons of grains are lost annually due to aflatoxin contamination [47]. In addition, more than four billion individuals in developing countries get chronically exposed to aflatoxicosis every year due to contaminated food consumption [48]. Such chronic exposure is largely attributed to heavy dependence on subsistence farming, unregulated local markets, and the lack of policy regulations on food and feed safety [49]. Consequently, the large aflatoxicosis outbreaks like those in Kenya and Togo claimed many lives [41] while survivors suffered from jaundice, leg edema, and hepatomegaly as well as malnutrition- related symptoms [50,51]. In fact, these outbreaks are traced to be originating from homegrown maize by subsistence farmers who have poor storage facilities [41] Typically, in this crisis 55% of maize products had contamination levels greater than 20 ppb, 35% had levels exceeding 100 ppb, and 7% beyond 1000 ppb [41]. Similarly, related cases were reported in India and China [52] which cases were all established after detecting the clinical signs of acute aflatoxicosis [48].

Effects of Aflatoxins on Human Health

Recognized as a risk factor for cancer [4], aflatoxicosis is characterized by adverse immunological and nutritional effects [48]. Among the aflatoxins, AFB1 and mixtures of AFG1, and AFM1 have been reported to be the major causes of chronic aflatoxicosis and human carcinogens [34]. Besides the carcinogenic effects, ingestion of foods contaminated with relatively lower aflatoxin levels over a long period has been reported to cause jaundice, liver cancer, chronic hepatitis [53], infertility, and impaired nutrient utilization in infants [54]. On the other hand, the ingestion of highly contaminated feeds results in acute hepatic failure, hemorrhages, digestion alterations, mental changes, and coma [48]. Besides direct chronic aflatoxicosis, aflatoxins have also been reported to complement hepatitis B in the causation of liver cancer [55]. Ultimately, the lack of policy regulations in developing countries of Southeast Asia and sub-Saharan Africa accounts for the high incidences of aflatoxicosis [41]. Such incidences, therefore, account for the fact that hepatocellular carcinoma is the fifth leading cause of cancer mortality in the world [56]. Therefore, this fact justifies the correlation between the high levels of aflatoxins contamination in maize with a high incidence of human hepatocellular carcinomas.

Biochemical Properties and Aflatoxin Metabolism

Given suitable conditions of 80-85% relative humidity and temperature of 28-35˚C up to 20 types of aflatoxins can be produced on a variety of feed substrates. However, among these naturally occurring toxins, aflatoxin B1, B2, G1, and G2 have been reported to be the most potent with aflatoxin B1 (AFB1) posing the highest degree of carcinogenicity [57]. Aflatoxins are characterized by high melting points of 260˚C and a thermal degradation temperature of 269˚C [58]. This implies that aflatoxins exhibit high thermostability although they can be decomposed by strong oxidizing agents. Aflatoxin metabolism plays the biggest role in determining the degree of toxicity in animal cells, especially in the liver [57]. The liver is considered the principal target organ for aflatoxins based on the first pass effect [59]. Since AFB1 is the most biochemically reactive, most research is focused on its metabolic pathways which justify its carcinogenic properties [57]. When aflatoxins are absorbed by the liver, they undergo biotransformation where AFB1 is metabolized through activation by cytochrome P450 enzymes to form the intermediate adduct AFB1-8, 9-epoxide. Characterized by its low stability, this adduct is responsible for the covalent modification of DNA, preferentially at the N7 position of guanine bases thereby affecting the complementary base pairing mechanisms [30]. Besides DNA modification, AFB1-8, 9-epoxide undergoes base-catalyzed reactions to form a more stable AFB1- 8, 9-dihydrodiol which is reported to be the most mutagenic metabolite [35]. In addition, Kellerman et al. reported that AFB1 can also be bio-activated to a highly active and labile intermediate AFB1 2, 3-epoxide, which reacts with various nucleophiles in the cell besides binding with DNA, RNA, and proteins [60]. Furthermore, according to [30]. Yunus et al. AFB1 can also be converted to hydroxylated metabolites (via monooxygenase’s) which are then metabolized to glucuronide and sulfate conjugate in the endoplasmic reticulum. Consequently, aflatoxicosis results in mutagenesis, carcinogenesis, and teratogenesis due to the alkylation of nuclear DNA by highly electrophilic adducts. In addition, chronic aflatoxicosis culminates into reduced protein synthesis, production of essential metabolic enzymes and structural proteins for growth [30] and immunosuppression hence poor poultry performance [61].

Aflatoxin Prevalence in Poultry Feeds

Aflatoxins are produced on a wide range of food commodities especially cereals and oilseeds which are the key ingredients in livestock feed formulation [62]. Identified as the third most consumed cereal worldwide [63], maize is most likely to be contaminated with aflatoxins at higher levels than any other feed ingredients [64]. Consequently, most of the maize-based poultry feeds in Uganda are highly contaminated with aflatoxins beyond recommended levels of 20 ppb [18]. The key predisposing factor to poultry feed contamination is poor post-harvest handling of maize which leads to high contamination levels by Aspergillus Flavus [65]. Such practices lead to high levels and prevalence of aflatoxin contamination in maize [66]. In addition, poultry feeds are stored at a relative humidity between 80% - 90% which is within the optimum range for fungal development [66]. Such conditions render the stored feeds more susceptible to fungal attacks within the normal feed storage time [32]. Whereas fungal contamination depends on postharvest handling, fungal development and aflatoxin production are dependent on storage time [66]. This implies that, as traders tend to hold maize back waiting for better market prices after harvest, high aflatoxin contamination is inevitable. Consequently, in an attempt to mitigate the aflatoxicosis-induced production declines, the Food and Drug Administration legislations set up an action level of 20 ppb as the maximum residue limit allowed in poultry feeds [67].

Effects of Aflatoxicosis on Poultry Performance

Effects of Aflatoxins on Chicken Physiology: Due to the heavy aflatoxin contamination of feed ingredients, commercial poultry is highly susceptible to chronic and acute aflatoxicosis [5,68,38]. Whereas acute is associated with the consumption of highly contaminated feeds [51], prolonged consumption of feeds with relatively low aflatoxin contamination levels is associated with chronic aflatoxicosis [69]. As a consequence, chronic aflatoxicosis is associated with poor feed utilization and increased susceptibility to microbial stress which is reflected in performance declines [70,47]. Furthermore, chronic aflatoxicosis has been reported to be the primary cause of teratogenicity, carcinogenicity, and mutagenicity as well as growth inhibitory effects in poultry [71]. These defects, therefore, result in biochemical, hemato [72] logical, and immunological alterations in the chronically affected poultry [73,74].

Effects of Aflatoxicosis on Feed Intake, Energy and Amino Acid Utilization: While feed intake and utilization are key determinants of poultry performance, aflatoxicosis has been reported to reduce feed acceptability, utilization, and enzyme efficiency [26,75]. In addition, aflatoxins interfere with calcium uptake and organic nutrient utilization in poultry while excess calcium impedes phytase enzyme activity due to insoluble complex formation with phytate phosphorous [76,77]. Furthermore, chronic aflatoxicosis decreases amino acid and energy utilization due to declines in cell metabolic efficiency [78]. Since the interaction between sulfur-containing amino acids and synthesis of aflatoxin B1-epoxide deter protein utilization and hence weight gain, it’s worth investing in available local options for sustainable aflatoxin decontamination for improved feed utilization [79].

Effects of Aflatoxicosis on Humoral Immunity and Organ Health: Besides hindering nutrient utilization, aflatoxicosis results in a reduction in antibody titers of Newcastle and Infectious Bursal disease as well as regression of the bursa of Fabricius [71]. This implies that, through regression of the bursa of Fabricius, aflatoxins interact with the T-cells to affect cell-mediated immunity in poultry to suppress vaccine efficacy [71]. In addition, a reversal in chemostatic inhibition of phagocytic abilities of leucocytes as well as heterophils has been reported to be associated with aflatoxicosis. Therefore, the synergistic effect of both antibody synthesis and phagocytotic suppression contributes to the increased response to environmental stress in poultry. Relative organ weight is a key indicator of organ health, whereas chronic aflatoxicosis has been reported to increase relative liver and kidney weights it results in the regression of the Bursa of Fabricius [80] In fact, the liver and kidney are considered to be the target organs for aflatoxicosis in all the affected species. As a consequence, the accumulation of nitrogenous wastes and aflatoxin metabolites results in histopathological changes as well as inflammatory thickening of the uterine mucosa in the tissues [80]. This implies that the reduced efficiency in nitrogenous waster excretion which results from liver and kidney damage greatly accounts for aflatoxicosis-related stress in poultry.

Effect of Aflatoxicosis on Layer Production and Eggshell Characteristics: Poultry layers are bred to convert feed nutrients into egg production rather than body muscles. Aflatoxicosis has been reported to reduce egg production without noticeable variations in layer weight gains [81,82]. Aflatoxicosis in layers has been reported to cause cytoplasmic vacuolation of the hepatocytes through impaired lipid transport and synthesis [83,84]. Such impairment is accompanied by lipid deposition in the liver, and suppressed lipid levels in the blood circulation [60]. This implies that aflatoxicosis induces phospholipid and cholesterol inhibition in the liver which results in far-reaching effects on layer performance [84]. Defined as the fastest bio-ceramic calcifying process among biological systems [85], eggshell strength is a key aspect in egg storage and transportation. However, aflatoxicosis has been reported to affect eggshell characteristics by interfering with the absorption and transportation of calcium and phosphorous [86]. In addition, aflatoxins have been reported to interfere with vitamin D3 metabolism [2,87] hence affecting calcium immobilization for eggshell development. Furthermore, chronic aflatoxicosis results in hepatic damage and a reduction in hepatic zinc levels in poultry [88]. Yet, the enzyme-dependent conversion of bone calcium into egg calcium is grossly affected by the generation and composition of zinc bicarbonate in blood circulation [89]. Therefore, in addition to aflatoxin decontamination, calcium supplementation through calcium bentonite clay inclusion may not only sequester aflatoxins but also possibly improve dietary calcium availability in layers.

Aflatoxin Decontamination Approaches: Whereas preventing feed contamination offers the best option it is practically impossible to get reasonable quantities of aflatoxin-free feeds. This implies that prevention of fungal contamination during harvesting and storage [11,90], as well as fungal growth inhibition, offer more practical solutions [11]. On the contrary, most of the poultry farmers in Uganda don’t produce their feed ingredients hence the lack of such phytosanitary adherence. This, therefore, leaves feed fortification and decontamination as the most practically viable option to control aflatoxicosis. Fortification of poultry rations with synthetic methionine alleviates aflatoxicosis-induced growth depression [91]. This is attributed to the ability of sulfur-containing amino acids to inhibit AFB1 mutagenicity and AFB1- epoxide synthesis during biotransformation [79]. Nevertheless, sulfur amino acids are some of the essential and limiting amino acids in poultry diets rendering this approach less cost-effective. Therefore, aflatoxin adsorption renders one of the most effective approaches since it reduces their bioavailability in the liver [11,22].

Consequently, since there is a relatively broader spectrum of nonnutritive aflatoxin sequestering feed additives decontamination remains an economically viable option. Besides amino acid fortification, biological approaches on the other hand can be used to absorb mycotoxins through enzymatic degradation and modification [92]. As a result, these characteristics led to the creation of biofilters for fluid decontamination and probiotics which also bind and remove aflatoxins [92]. However, such biological decontamination works mainly through sorption and enzymatic degradation making it a limited approach for biological systems [93]. Besides, biological control approaches developed for decontamination of aflatoxins in feeds have equally had limited attention and a multitude of criticisms as well [94]. Similarly, chemical decontamination using acids, salts, oxidizing, and reducing agents which require drying, and cleaning have equally had setbacks [11]. These setbacks are associated with the health decline of the animals and many chemical residues in animal systems [95]. However, Huwing et al. suggested that chemicals like calcium propionate successfully inhibited mold proliferation without affecting livestock health but with significant cost implications. For that reason, toxin decontamination using inorganic and chemically inert binders like some bentonites renders the most practical and economic approach.

Aflatoxin Decontamination Using Binders: The most cost-effective approach to aflatoxin decontamination known is deactivation using aflatoxin binders like activated carbon and bentonite clays [95,96]. However, the chemical structure of both the aflatoxin and the binder determines the effectiveness of adsorption and binder-aflatoxin compatibility [97]. The important characteristics of the adsorbent to be taken into consideration, therefore, include its physical structure, charge, pore size, and surface area [95] in addition to the inert effect on other livestock physiological processes. Consequently, given such requirements activated carbon and hydrated sodium calcium aluminosilicates (bentonites) stand out to be the most suitable candidates for aflatoxin decontamination. Identified as a general toxin adsorptive material with a high surface to mass ratio, activated charcoal has been reported to show great potential for aflatoxin decontamination in biological systems [98]. However, the effects of activated charcoal on livestock performance have been variable [11] while responses in poultry resulted in lower economic viability than clay-based binders [1]. Such challenges consequently rule out the possibility of using activated carbon as long as bentonite clays can technically substitute them. Aflatoxin decontamination by clay binders like bentonites on the other hand is associated with hygroscopicity, polarity, and solubility which favor aflatoxin intercalation with the bentonites in water [13]. This implies that, as the bentonite clay gets hydrated in the gastrointestinal tract, the polar water molecules weaken the interaction between the closely packed bentonite layers by lowering the charge density of the sequestered exchangeable cations such as Ca2+, Mg2+, Na+ and K+ [14]. Therefore, the mechanism of aflatoxin absorption is primarily through the exchangeable cations which neutralize the interlayer charges in aluminosilicates and are involved in the binding mechanism of aflatoxin B1 [21,13] and Hydrogen bonding [99,100]. Since hydrated sodium calcium aluminosilicates have a high affinity for aflatoxin specifically, this character results in the formation of strong aflatoxin-clay complexes hence adsorption [101]. However, the properties of bentonites vary from one geological deposit to another hence the need to test the efficiency of each batch of bentonites clays as aflatoxin detoxifiers [101].

Practical Methods of Aflatoxin Decontamination: The practicability of any aflatoxin decontamination approach depends on its effectiveness and the costs associated with its application. However, the application of physical, biological, and chemical methods of decontamination separately or in combination provides varying degrees of effectiveness [102]. While physical means are less practical, with biological methods the degrading microorganisms have limited degradation mechanisms and stability in the GIT at different pH levels [103]. This consequently leaves chemically inert bentonite clays as the most suitable adsorbents for aflatoxin sequestration. Defined as a smectite clay mineral generated from the crystallization of volcanic ash, bentonite clays adopt a sheetlike structure where double layers of tetrahedral sandwich an octahedral layer to make up individual sheets. They adopt negative charges which are derived from the replacement of Al3+ with divalent Ca2+ or Mg2+ ions. Then the sheets are interconnected by the exchangeable Na+ and Ca2+ whose predominance differentiates calcium bentonite from sodium bentonite [25]. Due to its absorptive and colloidal effects, bentonite is used as a filler in pharmaceuticals and oil purification as well as additives in livestock feeds. However, their utilization in livestock feeds is limited by the fact that their physiochemical properties which are its aflatoxin sequestration signature are highly variable hence the need for localized performance evaluations.

Characterized as hydrated sodium calcium aluminosilicates, bentonites effectively bind aflatoxins in the GIT hence preventing their absorption into the bloodstream [16]. Moreover, Hesham, et al. [ 23] and Shi, et al. [33] reported an improvement in body weight gain and feed conversion ratio of broilers fed on diets fortified with bentonites. Consequently, this effectiveness of bentonites is attributed to the expanding clay lattice, interstitial water, exchangeable cations hence the aflatoxin binding ability [14]. In addition, bentonites have been also reported to be efficient against a broad spectrum of mycotoxins making them more suitable for the most frequent cases of multi-contaminated feeds [104]. Using bentonite clays hence targets binding the aflatoxins and prevents them from being absorbed from the animal’s digestive tract, and then excreting them through the fecal matter [90,13]. Characterized by the ability to form stable complexes with aflatoxins at temperatures between 25 ºC and 37 ºC, bentonites clays are capable of adsorbing aflatoxins under the condition in the GIT [105] (Magnoli et al., ). As a result, certain bentonite at 0.5% inclusion levels was able to reduce aflatoxin bioavailability in broilers [21,23]. However, bentonite clays from several sources have been reported to improve pellet stability [11] and poultry performance through aflatoxin decontamination but with varying degrees of effectiveness [105]. This implies that the different bentonite deposits in the Albertine Graben region of Uganda can provide a potential solution to feed AF decontamination [105]. However, the variation in properties among bentonites warrants assessing the performance.

The Existing Knowledge Gap: The high affinity for aflatoxins by the bentonites justifies their utilization given the high levels of aflatoxin contamination in the poultry feeds [8]. However, the aflatoxin decontamination potential among bentonite clays is highly dependent on the geographical location and nature of the bentonite clay parent materials [105]. Consequently, there is inconsistent and insufficient information about the inclusion levels of the different bentonite clay in poultry diets [9]. In addition, none of the previous studies has compared commercial aflatoxin binders with other bentonite clays as well as establishing the optimum inclusion levels of Albertine bentonite clays. Yet, beyond certain optima, bentonite clays are hypothesized to hinder nutrient utilization alongside the negative effects of excess calcium for the case of calcium bentonite. Furthermore, due to the transfer of aflatoxins and their metabolites to poultry edible products and their effect on human health, efforts have been made to set contamination limits of 20 ppb. Therefore, studies towards the exploitation of this resource are necessary since Uganda is endowed with huge bentonite deposits in the Albertine region [9].

Conclusion

The authors systematic review of the available aflatoxicological studies in poultry whose products are the most widely consumed among livestock products demonstrates that the majority of the studies proved a significant effect of aflatoxicosis on commercial poultry performance, carryover in products, and hence human health. The relationship between egg production and aflatoxin decontamination indicates a great reduction in the laying performance of poultry layers due to chronic aflatoxicosis. The most effective approach to combating the effects of aflatoxicosis is the use of readily available innert adsorbents like bentonites. However, it may suggest that the inclusion of such adsorbents be informed by localized feeding trials.


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