NK/T Lymphoma of Nasal Type in a Patient with an HIV Infection

NK/T Lymphoma of Nasal Type in a Patient with an HIV Infection

Introduction
The NK/T lymphoma of nasal-type it’s a rare disease, presented more frequently in men between the ages of 50 and 60 years old [3], they represents almost 6-7 % of all nonhodgkin’s lymphoma (NHL) and it’s mostly found in regions like the Southeast of Asia, this percentage changes in the United States reaching 1.5%, in Mexico there has been reports of a high prevalence in respect to other regions, nevertheless more precise statistics are needed [4,5] . There’s a lot unknown in respect to its etiopathogenesis and it comprehends a variety of oncogenic paths, its development is associated invariably to the Epstein-Barr Virus [6]. The diagnosis of such disease is made after clinical suspicion, they can have nasal obstructive symptoms, necrotic lesions and diverse upper airway symptoms by compression of adjacent structures and general symptoms, the approach covers a broad spectrum of extensive studies where we can highlight the PET scan [6,7]. The golden standard are the morphological findings (polymorphic infiltration of atypical lymphoid) and immunohistochemistry (CD2, CD56, cytoplasmic CD3, granzyme B, TIA-1, and perforina) taking from 6 to 8 biopsies from different places due to the usual existing necrosis and if possible identify the charge of the Epstein-Barr virus that also has a biomarker prognosis implication [5,8]. Regarding treatment there’re still research about it, in phase I/II studies the preference is a combination of radiation therapy with chemotherapy [3].

For phase III/IV studies Chemotherapy is the foundation of the treatment. The principal agent in Chemotherapy is L-asparaginase, currently there are no conclusive data about immunotherapy or hematopoietic Stem cells [6,8]. The role of the human immunodeficiency virus in combination with said neoplasia seems to cause a rapid progression of the disease without definition of the etiopathogenic paths, there exist only a few reported cases [9,10].

Case Presentation
Mexican male of 48 years old without oncological family history, without precedents of chronic diseases or use of medicines and denial of history of STDs risk, goes to check up due to progressive dysphagia to solids, halitosis, nasal voice, nausea, fever, weight loss of over 10% body weight, asthenia and adynamia. Oral cavity exploration with necrotic ulcer in soft palate, posterior green-green-is discharge, congestive turbinates, otoscopy revealed hypomobility of both tympanic membranes, rest of exam without relevant foundings. Laboratory studies reveal pancytopenia. Tomography reveals enlargement of the mucous of the left maxillary antrum, the ethmoidal cells and the left sphenoid sinus; In abdomen the image revealed multiple renal calcifications and splenomegaly. ELISA and Western Blot positive for HIV. A biopsy of the nasopharyngeal tumor is taken and it reports NK/T lymphoma of nasal-type with positive CD-56. During Hospital stay the diagnostic and therapeutically approach are limited due to septic shock due a pulmonary infection with a torpid evolution and the patient dies in the IC unit Figure 1.

Figure 1: a) Cellular infiltrate of atypical lymphocytes. 40x lense
b) Ocre halo around the lymphocyte, positive staining CD56 +
c) CD8+
d) LMP 1+, membrane antigen associated with EB virus infection.
Discussion
The NK/T lymphoma of nasal-type is a rare affection associated with a bad prognosis, it was described in 1933 as a malignant midfacial granuloma and since 2016 is being referred with the modern nomenclature by the World Health Organization (WHO) in its classification of lymphoid malignancies, it constitutes from 1.5 to 7% of all non-Hodgkin lymphomas and presents a marked prevalence in some areas like Southeast Asia and Central America [4,5,8]. Usually it produces nasal obstruction due to invasion of sinuses and nasal cavities, it can coexist with epistaxis, nasal discharge, odynophagia and general symptoms. The emphasis on suspicion and intentional diagnosis radícate in the importance of early treatment [4,6]. It is more frecuente in males and the sixth decade of live [3]. Histologically the cells show a pattern of angiocentric growth, which causes vascular obstruction and necrosis, immunophenotypically, the tumor’s cell show CCD2, CD56, cytoplasmic CD3, granzyme B, TIA-1, and perforina [6- 8]. Characteristically i invades middle line structures and its bad prognosis has reported grave and fast progression when associated with HIV infection [9-11]. Even though some of its etiopathogenesis mechanisms are known, and the invariable relation to EB virus [6], there’s still a lot of information lacking on the lymphotropic role of HIV. The intermediate and high grade lymphomas are the most frequent ones in HIV patients, the frecuente can increase up to 165 times in comparison to immunocompetent [10], In that regard there are some cases in which association with NK/T lymphomas has not been found as reported by Catteneo et al., Nevertheless the role of EBV is not frequent in immunocompetent patients [12], which is why most fatalities can be associated to a synergy of viral mechanisms and a state of immunosuppression. It’s important to broaden the study of such a cases to anodize the variables that could interfere with the correct statistic rigor to determine possible associations. The lack of information on the subject could affect the survival or complications of the patients such as the one presented.

Conclusion
It’s unknown in its entirety the pathogenesis of the NK/T nasal-type extranodal lymphoma cells, it is known that is strongly associated with the infection of Epstein-Barr virus and a more aggressive course in immunocompromised patients, like in this case, there should be more research to determine if there is a pathogenic relation between TNK lymphoma and HIV to explain the results found in the literature.

Electrical Enhancement of Bone Osteogenesis Using a Totally Implantable DC Battery Disc 1.5V-https://biomedres01.blogspot.com/2020/10/electrical-enhancement-of-bone.html

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Electrical Enhancement of Bone Osteogenesis Using a Totally Implantable DC Battery Disc 1.5V

Introduction

Any mechanical stress applied on bone results in the generation of electrical potentials which exerts some level of effect on bone healing [1-3]. In subsequent studies, the significance of electrically stimulated osteogenesis was evaluated experimentally [4,5] and clinically [6-8]. It has been shown that bone is formed under electronegative potentials and resorbed under electropositive potentials [9]. The objective of this study was to evaluate the effect of an implanted modified disc battery 1.5 V as a direct current electro-stimulator (Cathodic Inductive Coupling) on fracture healing.

Materials and Method

Silver oxide disc batteries 1.5V connected with resistors were used. The driving electrodes were 2 cathodes and one anode of 0.5mm diameter stainless steel wire and discharging a constant direct current of 25μA. The batteries were encapsulated in a silicone case and sterilized by ethylene oxide gas (Figure 1). The right femur of 2 adult anesthetized mongrel dogs was osteotomized in the mid-diaphysis. Each osteotomized femur was subjected to internal fixation by a compression dynamic plate and cortical screws for 8 holes. The wires of the cathodes were then connected to the nearest screws of the bone plate on either sides of the fracture osteotomy site. The wire of the anode and the battery were left under the skin. The left femurs of the same dogs were similarly treated but without batteries as a control. The current could be monitored by a sensitive galvanometer over the operation site. The animals were kept in their boxes and radiography was done at bi-weekly intervals. They were euthanized after 8 weeks for histological studies.

Figure 1: The encased battery with 2 insulated cathodes and one anode.

Results and Discussion

In this trial, radiological and histological results indicate the marked osteogenic response in electrically stimulated fractures with implantable disc batteries (Figures 2 & 3). In this trial, using the nearest cortical screws to the fracture line for cathodic stimulation by a such simple, low coasted method initiated an electrical field within the fracture site by inductive coupling. The negativity of the fractured bone might be augmented since the ohmic resistance of the osteosynthesis plate and screws is un remarkable. Inductive coupling was shown to enhance osteoblast differentiation and proliferation by mechanisms involving alteration of growth factors [10], gene expression [11] and trans-membrane signaling [12]. Despite variations in the methods used for electrical enhancement of bone healing, similar positive results have been reported [13-16]. Furthermore, electrical stimulation produces osteogenesis significantly helps union where impaired bone healing exists and can be used in a wide variety of problems: delayed union and nonunion of bones with or without chronic infection and in failed posterior spinal fusion [17,18]. This work opens new doors for more investigation on high number of clinical cases and the duration required to assess the effectiveness of this methods.

Figure 2: Radiograph of electrically stimulated fractured femur after 4 weeks with the battery (blue arrow).

Figure 3: Periosteal and Endosteal activity. A. Electrically stimulated ( blue arrow); B. Control

Analysis of 2 Cases of Puncture and Suction of Intrauterine Exudate Guided by Transvaginal B-Ultrasonography during Early Pregnancy-https://biomedres01.blogspot.com/2020/10/analysis-of-2-cases-of-puncture-and.html

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Analysis of 2 Cases of Puncture and Suction of Intrauterine Exudate Guided by Transvaginal B-Ultrasonography during Early Pregnancy

Introduction

More attention is paid to intrauterine exudates that occurred before embryo transfer or before artificial insemination. However, there were less reports of intrauterine exudate after pregnancy and many of that were not strictly distinguished from abortion [1]. To distinguish from abortion, intrauterine exudates during early pregnancy in our center was defined as follows:

a) patient with high risk factors such as history of intrauterine exudate or leakage, hysteromyoma, adenmyosis or OHSS after ovarian stimulation,

b) patient without vaginal bleeding,

c) B-ultrasonography shows fluid. Sonolucent area in uterine cavity rather than hypoechoic sonolucent area because of cavity bleeding.

Two cases of intrauterine exudate occurred during early pregnancy after the IVF-ET in this paper and the number of intrauterine exudates developed progressively. There was a history of repeated IVF-ET failures in one case and repeated abortions in another case. To avoid embryo loss, puncture and suction of intrauterine exudate guided by vaginal B-ultrasonography was performed and permitted by the Hospital Reproductive Medical Ethics Committee and patients. The process is described as follows.

Case Materials

Case 1

A 29-year-old woman was treated for sequela of pelvic inflammatory disease and adenmyosis. She had a history of bilateral salpingectomy and underwent 4 times of IVF-ET from 2015 to 2016 in our hospital. A small amount of fluid was found in the uterine cavity on the day of embryo transfer every IVF-ET. One developed an ectopic pregnancy and the remaining 3 failed. In April 2017, the luteal phase ovarian stimulation was performed again, AMH 1.49ng/ml and 5 oocytes were obtained and there were 3 transplantable blastocysts on day 5. In July 2017, Frozen Embryo Transfer (FET) was carried out in a modified natural cycle. On the HCG day, the endometrium was 8.5mm and E2 was 1448.0 pmol/ml. Three blastocysts (5B-C, 3B-B-, 3BB) were transferred on day 5. the endometrium was 7.4mm. And the echo of uterine cavity was uniform. β-HCG was 266.6 mIU/ml and the progesterone were >190.8 nmol/ml after 10 days. the maximum anterior-posterior diameter (APD) of the separation of uterine cavity was 7.0 mm. Puncture and suction by transvaginal B-ultrasonography via the fundus of uterine cavity was performed on the same day due to the great possibility of early abortion. The suction continued for 10 seconds with the negative pressure of 80mmHg.

About 0.5ml of white exudate was drawn out and no embryonic structure was found in the exudates under microscopy. B-ultrasonography showed APD 1.0mm after the operation. The level of β-HCG was 5333.0 mIU/ml, B-ultrasonography showed APD 5.0 mm after 3 days. The same operation was performed again. Approximate 0.4 ml of reddish exudates was drawn out and APD was 1.0mm after the suction. After 15 days, B-ultrasonography showed intrauterine twin pregnancy and the intrauterine exudates was still present. APD was 4.5mm. The third same operation was performed, and approximate 0.4 ml of reddish exudates was drawn out and APD was about 1.0mm after the suction. Oral cephalosporins were given to prevent infection during all the three suctions. There was no transvaginal bleeding or fever after the operations. At 12 weeks of gestation, NT B-ultrasonography showed intrauterine twin pregnancy, central placenta previa and disappeared intrauterine exudates. The placenta previa became marginal after 20 weeks of gestation. Two healthy baby boys have been delivered.

Case 2

A 41-year-old female was treated for expected low ovarian response accompanied by hysteromyoma and endometrial polypectomy. She has a history of 2 spontaneous abortions for unknown reason. In December 2016, the luteal phase ovarian stimulation was performed, 5 oocytes were obtained, and 2 blastocysts (3B-B, 3BB) were obtained on day 5. FET was carried out in a modified natural cycle in August 2017. The endometrium was 9.0 mm on the HCG day. It was 9.0 mm and intrauterine exudate was not found on the day of transfer. Two blastocysts were transferred on day 5. Blood β-HCG was 635.6 mIU/ml and the APD of uterine cavity effusion was 2.0 mm after 11 days. Three days later, APD increased to 8.0 mm. Puncture and suction by transvaginal B-ultrasonography was performed in the same way as above-mentioned. 0.7 ml of white exudate was drawn out and the APD was 1.5 mm after the suction. β-HCG was 3887.0 mIU/ml and APD was 6.5 mm after 6 days. The suction was performed again. 0.5 ml of reddish exudate was drawn out and APD was 1.0 mm after the suction. B-ultrasonography showed that APD was 2.0 mm after 4 days and an 8×6×7 mm intrauterine gestational sac was detected. Vaginal bleeding occurred after 7 days. B-ultrasonography showed that the gestational sac had been lost.

Discussion

The incidence of intrauterine exudate or leakage before embryo transfer is 4.2% to 11.1% [2]. It is common in patients with tubal effusion, PCOS, OHSS, hysteromyoma, adenmyosis, intrauterine infection, etc [3]. Its occurrence is mostly related to hyper-physiological hormone level, fallopian tube factors, immunological abnormality and relevant changes of the intrauterine microenvironment [4]. The intrauterine exudates after IVF-ET during early pregnancy is rarely reported and is difficult to distinguish it from intrauterine bleeding because of abortion. The reason for the occurrence is like the above. And the expectant or conservative treatment for intrauterine exudates is generally taken. The intrauterine exudates is usually assessed by APD. The expectant or conservative treatment is mostly used in patients who produce intrauterine exudates in a short time. In our center, patients with with APD < 3.0mm were treated appropriately with glucocorticoids, cephalosporins, and baotailing tablets (a traditional Chinese medicine).

The intrauterine exudates can disappear within 2 weeks in the majority of patients. Several studies have suggested that when excessive intrauterine exudate exists, that is, APD ≥ 3.5mm, the exudate will hardly disappear in a short time, and it will have a negative impact on the clinical outcome of IVF-ET, especially in patients with tubal infertility or with persistent intrauterine exudate on the day of embryo transfer. Embryo transfer should be cancelled in this situation [5]. Intrauterine exudates occurred during early pregnancy after FET in both cases and no treatment was reported when the intrauterine exudates was persistent and APD was >3.0mm. Because the patients’ estradiol was <2000 pmol/L on the HCG day, the intrauterine exudates may be related to adenomyosis in the first case, and the another to hysteromyoma companied with polypoid hyperplasia of uterine cavity in the second case. APD was > 3.0 mm during the early pregnancy and persistent and there had been a history of multiple failures of IVFET and a history of recurrent abortion which meant high probability of abortion during early pregnancy. APD value did not reduce after conservative treatment. Therefore, it is decided to take further treatment to keep pregnancy. Intrauterine suction by transcervical cannulation is usually used to eliminate exudate before embryo transfer [6].

It was not reported after embryo transfer and the reason is that it is easy to damage the newly implanted embryo because it is difficult to control the negative pressure and area of suction. The puncture and suction guided by transvaginal B-ultrasonography was adopted to minimize the damage to the embryo after discussion.

The reasons are as follows:

a) The area of suction by puncture is easier to be controlled and more limited than that by transcervical canal cannulation,

b) The negative pressure and the time of suction is constant and can be controlled in a safer range;

c) We have the similar experience from multifetal pregnancy reduction by transvaginal B-ultrasonography. The puncture damage to uterine can be ignored.

d) The probability of stabbing the newly implanted embryo is low after selecting the direction of the puncture.

The exudates were significantly reduced after 2-3 times of puncture and suction in the 2 cases of intrauterine exudates.

Two babies have been delivered in one case, and miscarriage occurred in another case. The analysis of above two cases means that this method is more feasible and safer than intrauterine suction by transcervical canal cannulation for the treatment of massive intrauterine exudate during early pregnancy. It is an innovative treatment of intrauterine exudates. Of course, there is something to be improved. For viscous intrauterine exudates, it could be considered to inject a small amount of α-chymotrypsin to decompose and dilute the intrauterine exudates, in order to facilitate the suction.

Regional pH Change in Groundwater Between Field and Laboratory Analyses, Temperature, Groundwater Silicon, Agricultural Soil pH and Soil Type Distribution in Finland-https://biomedres01.blogspot.com/2020/10/regional-ph-change-in-groundwater.html

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Regional pH Change in Groundwater Between Field and Laboratory Analyses, Temperature, Groundwater Silicon, Agricultural Soil pH and Soil Type Distribution in Finland

Regional pH Change in Groundwater Between Field and Laboratory Analyses, Temperature, Groundwater Silicon, Agricultural Soil pH and Soil Type Distribution in Finland

Introduction
Silicates are known as a part of carbonate-silicate cycle [1], but the role of silicon (Si) in pH regulation of groundwater and agricultural soil (soil) is not as well clarified. Stability in inter-regional relative pH values has suggested on the possible role of silicon (Si) in pH regulation [2]. Soil pH has been written to associate non-significantly positively with Si.gw in continental Finland [3], but pH.soil was highest in Åland, where Si.gw was low [4]. In combined regression by [Temp; pH.soil] pH coefficient got negative value for Si.gw [5]. Åland has been excluded from this survey because the availability of Si seems not to be associated with Si.gw [4,6]. Groundwater pH is different in immediate analysis on the field (pH.gw.field) to the laboratory survey (pH.gw.lab). The purpose of this assessment is to describe this difference (Δ. pH.gw) and to propose explanations.

Materials and Methods
Groundwater parameters (concerning springs and dugwells) are from Groundwater database © Geological Survey of Finland 2017 [7]. pH values and soil-type proportions from cultivated fields separately from 19 Rural Centers (RC, earlier Agricultural Advisory Centers), concerning period 1986-90 are provided by Eurofins Viljavuuspalvelu Oy [8]. Number of soil samples was 552,788. The boundaries, names and numbers of RCs and Regions deviate slightly from each other [9]. Average annual temperatures of RCs from 1981-2010 are visually approximated by combining map of Finnish Meteorological Institute [10] and map of RC´s [11]. Regional values for “Varsinais-Suomi” we got by combining RC values of “(03). Varsinais-Suomen” and “(4b). FinskaHushållningss ”and for “Uusimaa” by combining RC values of “(01).Uudenmaan” and “(02).NylandsSvenska” as in [4]. After this RC values were given for respective Regions. Numerical data are in Table 1.

Table 1: Regional temperature, groundwater (gw) pH in field and laboratory surveys, pH of agricultural soils, gw pH difference ( Δ.pH.gw), Si.gw, proportionof organic and coarse mineral soil-types. (Åland excluded from calculations).
Results
In general values of pH.gw.lab (6.67 +/- 0.18), were the highest, pH.gw.field (6.45 +/- 0.17) the second highest. Values of pH.soil (5.86 +/- 0.14) were the lowest. Only in one of 19 regions pH.gw.field was higher to pH.gw.lab (in Ostrobothnia). Mean regional Δ. pH.gw was 0.31 (+/- 0.21), maximum 0.64 and minimum -0.31 (Table 1). pH.gw.field and pH.gw.lab associated weakly positively with each other (r = +0.29) (Figure 1), as well as with Temp (+0.17 and +0.20, respectively) (Table 2). pH.gw.field associated significantly (+0.64) with Si.gw (Table 2) and mirror-like with pH.soil (r = -0.12) (Table 2) and (Figure 2). pH.gw.lab correlated weakly inversely with Si.gw (r = -0.11) (Table 2) and moderately positively with pH.soil. (r = +0.41, p = 0.091) (Figure 3)- oppositely to pH.gw.field (Table 2).

Table 2: Pearson correlations in inter-relations of Temp, pH.gw.field, pH.gw.lab, their difference (Δ. pH.gw), Si.gw, pH.soil. (approximates, because invisible decimals were not rounded).
Figure 1: pH.gw.field and pH. gw.lab.
Figure 2: pH.gw.field pH.soil.
Figure 3: pH.gw.lab. pH.soil.
Δ. pH.gw correlated (Table 3) as pH.gw.lab, but stronger – inversely – with Si.gw (-0.62**) (Figure 4) and positively with pH.soil (+0.45) (Figure 5) Si.gw correlated weakly (+0.11, ns), but interestingly with pH.soil (Figure 6).(Regression by) [Temp; Δ. pH.gw] explained variation of pH.soil 79.4 % (r = 0.89, p < 0.001), coefficient (direction)s (+/+) (Figure 7) and by [Temp; Si.gw] 80.6 % (r= 0.90, p < 0.001) coefficients (+/-) (Figure 8).[Prp.org;Prp. coms] explained trend-like Δ. pH.gw. Visual association is clear, although association is non-significant, coefficients (-/+) (Figure 9).

Table 3: Significances of correlations.
Note: Symbols *, ** or *** are signs of significance level.

Figure 4: Δ. pH.gw and Si.gw.
Figure 5:Δ. pH.gw and pH.soil.
Figure 6: pH.soil and Si.gw.
Figure 7: Combined regression of PH.soil by Temp and Δ. pH.gw in continental Finland.
Figure 8: Combined regression of pH.soil by Temp and Si.gw in continental Finland.
Figure 9: Combined regression of Δ. pH.gw by Organic and coarse mineral soil type proportion in continental Finaland.
Discussion
Because generally only pH.gw.lab values are published [7] and I have not find discussions on differences between Finnish pH.gw.lab and pH.gw.field, this assessment can be justified. The primary aim was to describe the pHenomenon by (Figures 1-8) and secondarily to propose some explanations. CO2 values, which were measured only on the field, were not available for this survey. HCO3 - values, which were measured in the laboratory, were available, but they seem not to be informative without CO2. Regional Temp (average mean annual temperature) was significantly (p < 0.01) associated with Si.gw and pH.soil, weakly with pH.gw´s and infinitesimal with Δ. pH.gw (Table 2). Temperature was strongly associated with Finnish geography and soil-type variation [3,4,5]. Here Temp association with Prp.org was -0.88, with Prp.coms -0.51 and with proportion of fine mineral soils (Prp.fims) +0.72. calculated from (Table 2). (Prp.coms +Prp.org + Prp.fims = 100). Interesting was the low association of Temp with pH.gw parameters; especially Δ. pH.gw seems to be “thermo-resistent”.
pH.gw.field associated significantly positively with Si.gw (+0.64**) and negatively with Δ.pH.gw (Figure 2). pH.gw.lab associated about oppositely: significantly positively with Δ. pH.gw (+0.63**) (Figure 3) and weakly negatively with Si.gw. pH.gw.field curve forms like a mirror image with pH.soil (Figure 2), similarly as Si.gw with Δ. pH.gw (Figure 4). Interesting was that pH values of different soil-types (org, sands, mould, moraines and silt) gave highly similar curves as pH.soil [8]. pH.soil associated about similarly with pH.gw.lab and Δ. pH.gw (Figures 3&5). It is interesting, because proportion of agricultural soils of total land is different in different parts of Finland. This suggests that gw could be mainly of intra-regional origin. Regression of Δ.pH.gw by [Prp.coms;Prp. org] (Figure 9) showed trend-like positive association with coms and negative associations with org. Soil-type distribution (Figure 9) did not explain Ostrobothnia nor North Karelia values (Figure 9).
Combined regression by [Temp;Δ. pH.gw] explained pH. soil 79.4 % (r = 0.89, p < 0.001), both parameters were positive (Figure 7). [Temp;Si.gw] explained it slightly stronger 80.6 % (r = 0.90, p < 0.001), coefficients (+/-) (Figure 8). The negative association of Si.gw with pH. soil in this combination can be understood by Figure 6 (similar trends with Temp, but Si.gw fluctuations/deviations were like mirror-image to pH.soil). Δ. pH.gw could be associated with carbonic acid (H2CO3): Its pKa1 is 6.3 [12], which is near the means of pH.gw.field (6.45) and pH.gw.lab (6.76). This pKa1 includes reactions CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3 - [13]. Most of CO2 is dissolved in water and about ca 0.2 % of CO2 is in the form of H2CO3 [13,14]. In the absence of a catalyst, the balance in reactions CO2 + H2O ↔ H2CO3 is reached quite slowly [13]. Slow evaporation of CO2 after pH.gw.field analysis could reduce H2CO3 and raise pH.gw. The effect of temperature as such on pH.gw (on the field 7.2 +/- 3 °C) [7] can obviously be excluded, because even pH.gw.field was measured at 25°C as pH.gw.lab [7].
Explanations via silicon: Silicate weathering can proceed via the chemical reaction as: CaSiO3 + 2CO2 + H2O ↔ Ca2 + + 2HCO3 - + SiO2 (dissolved silica) [1]. So silicates can sequestrate CO2 from air, soil and subsoils and work as antacids, before coming to groundwater. Possibly in gw this reaction could work slowly backwards [1] and produce again water-soluble CO2, which could evaporate as CO2 in the temperature (25°C), which is higher to the fresh gw and so raise pH. Inside every region Δ. pH.gw of different samples could be different with different explanations (i.a. different buffer systems). Low pH.gw in North Karelia as in Ostrobothnia (with acid sulpHate soils [15]) could be a part of explanation. Regional Δ. pH.gw medians got no negative values, but zero in Ostrobothnia . Product of soluble SiO2, orthosilicic acid Si(OH)4 or H4SiO4 –is a weak acid (pKs1 = 9.51 and pKs2 = 11.74) [16,17]. Si(OH)4 can condense and form dimers and oligomers [18]. The pK of silanol (Si-O-H) [19] groups on the outside of oligomers 1nm in diameter is 6.8 [18], which is close to the mean pH.gw`s, which could make buffering possible. Because pKa2 (7.20) of phosphoric acid is moderately near mean PH.gw’s, it could have some effects, too [20].

Conclusion
Regional Δ.pH.gw was associated inversely with Si.gw. Combined Temp and Δ. pH.gw explained ca 80 % of agricultural soil pH variation. Δ. pH.gw can be associated with silicate carbonate interactions. (CO2 sequestrating by silicates - weathering - can be seen as a pH stabilizing process, which could be supported by silicate liming agents and fertilizers, e.g. industrial slags and stone meals).

A Review of Factors Affecting Nursing Turnover in Japan-https://biomedres01.blogspot.com/2020/10/a-review-of-factors-affecting-nursing.html

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A Review of Factors Affecting Nursing Turnover in Japan

A Review of Factors Affecting Nursing Turnover in Japan

Introduction
At present, the Japanese health system, like most countries, significantly depends on nurses delivering quality care to individuals, families, and communities. Nurses comprise the majority of health professionals in Japan; Table 1 shows that out of 2,029,242 health professionals, almost 70% are nurses (including both registered and enrolled nurses). Thus, nursing shortages can prove costly and detrimental to a nation’s health system [1]. Closely related to nursing shortages is nursing turnover, which can negatively impact the health sector’s capacity to satisfy patient needs and provide quality care [2]. A high turnover rate can affect nurses’ wellbeing and productivity [3]. Hence, for these reasons, a continuous supply of nurses is imperative to the wellbeing and progress of Japanese society. A better understanding regarding nursing turnover is necessary to adequate address this growing problem. Thus, the present paper includes a systematic review of nursing turnover in Japan.

Table 1: Employed health professionals in 2012.
Source: Ministry of Health, Labor and Welfare n.d.

Definition of Key Variables and Relationships
Turnover refers to the movement of individuals within an organization, profession, or industry. In general, turnover is understood as the rate at which employees leave a company or organization and are replaced by new people [4]. A high nurse turnover rate has been associated with dissatisfaction [5]. Job satisfaction refers to how a person feels about various aspects of his or her employment [6] and has been identified as a factor contributing to an employee’s intent to leave and job turnover [7]. “Intent to leave” refers to an employee’s plan to quit his or her existing job and/or find another job, whether in the same or different profession [4]. The intent to leave is a critical factor in predicting nursing turnover [8]. Turnover is highly related to burnout, which is linked to job dissatisfaction. Burnout is the severe physical, emotional, and mental fatigue experienced by individuals on the job. Nurses, for example, are at high risk for burnout due to the intense nature of providing multi-pronged medical care [9].

Turnover and Nurse Availability
The number of nurses has increased in Japan. Between 2002 and 2014, nurse employment rose by 30%, from 1,163,393 to 1,506,380; however, this was not sufficient to meet the nursing demand of 1,623,800 in 2014 [10-12]. By 2025, it is estimated that nursing demand will rise to 1,844,000. However, the nurse supply is expected to remain short of this demand [13], especially within small and medium-sized hospitals. Competition for nurses tends to result in larger hospitals paying higher salaries and attracting a greater number of nurses than smaller ones [14]. Due to the discrepancy between nursing supply and demand, concerns over shortages have risen. According to statistics from 2012, roughly 191,000 registered nurses joined the profession, which includes around 47,000 newly qualified nurses (and around 144,000 with prior experience rejoining the workforce or transferring). However, roughly 161,000 left the profession, with turnover being higher in large cities [15]. Throughout Japan, this nursing shortfall creates several healthcare delivery challenges. This is even more problematic as the gap between supply and demand is not estimated to decrease any time soon [15].

This nursing shortage in Japan is primarily the product of high turnover. However, high nurse turnover is not just a problem in Japan. Other countries, such as the United States, Great Britain and Germany, are also dealing with this issue [16-20]. Research into the factors contributing to nursing shortages, and strategies to address such shortages, is needed. Currently, there is no synthesis of evidence available to help guide strategies for preventing nursing turnover. Thus, the goal of the present paper was to conduct a review of published reports describing the factors contributing to nursing turnover in Japan.

Methods
CINAHL, MEDLINE, ProQuest Health & Medical Collection, PubMed and Google Scholar were used to conduct a regimented literature review. Papers published between 2006 and 2016 were analyzed to determine relevancy. Papers were chosen from this time period since work environments dramatically change each year, and new technology continues to be introduced. Therefore, it seemed appropriate to review papers published in the last ten years in order to have an overview of changing contexts, as well as current factors, affecting nursing turnover in Japan. The following search terms were used: ‘intent to leave’, ‘turnover’, ‘burnout’, ‘job dissatisfaction’, ‘nurse’ and ‘Japan’. The last date of access for all databases was 1-6-2017. In the case of Google Scholar, the number of hits was inordinately high; therefore, another search was conducted combining the keywords, which yielded 204 papers for possible inclusion (Table 2). To assure review quality, PRISMA guidelines [21] were employed. During identification, 500 papers were initially deemed relevant, including nine additional papers culled from the reference lists of retrieved papers. During the screening process, duplicate and irrelevant papers (determined by assessing titles and abstracts) were excluded.

Table 2: Records retrieved from sources.
During the eligibility process, full-text articles were assessed. Consequently, 10 studies were included in this review. Table 2 details the number of papers initially retrieved through database searches, while (Figure 1) highlights the screening process, with a detailed number of references based on PRISMA guidelines. A metaanalysis was initially considered for the present review; however, as the included studies were highly heterogeneous, an adequate metaanalysis could not be pursued. Consequently, a narrative synthesis methodology [22] was applied. Therefore, the results section of each paper was considered thematically, and common themes were determined. Furthermore, to assure review quality and to avoid bias, qualitative studies were assessed applying the Critical Appraisal Skills Programmed method [23], and non-experimental studies were assessed using Law’s Critical Review Form [24].

Figure 1: Preferred reporting diagram for systematic reviews & meta-analyses (PRISMA) showing selection for review.
Results
A summary of the reviewed studies is shown in Table 3. Five of the 10 papers were quantitative, four were qualitative, and one paper employed mixed methods. The papers covered a range of settings, including urban and rural hospitals with different bed capacities (ranging from 50 to 700 beds). The present results are described according to key variables of interest, including intent to leave, turnover, burnout, and job dissatisfaction. Across all papers, factors contributing to nurses quitting their job and/or their profession are discussed. Each paper addresses factors leading to a job/career exit and the main factors impacting the exit. A thematic analysis was identified as contributing to nurses’ decision to leave either their job or, more significantly, the profession. These factors are outlined in Figure 2.

Table 3: Summary of studies included in the synthesis.
Figure 2: Factors associated with burnout, poor job satisfaction or intention to leave.
Personal Factors
Perceived unsuitability to the job: When a nurse believes he or she is unsuitable to his or her profession, he or she is likely to leave not only the job but also the profession [25]. While many individuals pursue nursing during their university studies, realities of the job or profession can lead to reservations regarding this chosen career path. Unsuitability to the job or profession has been identified as leading to nurse turnover, especially among newly graduated nurses [26-30]. A lack of understanding regarding the role of a nurse also appears to contribute to one’s intent to leave [31].

Age and Position: Age has been identified as a factor affecting an individual’s values at work and attitude toward his or her nursing role. Individuals of different ages have different value systems, and these value systems impact reasons for leaving an organization and/or profession [32]. For younger nurses born after 1975, losing confidence in their ability to care for patients seems to contribute to the intent to leave. Rank also appears to affect the intent to leave. For instance, more senior nurses are less likely to leave the profession [33]. Younger and more junior nursing professionals are more likely to leave their job and/or profession.

Inexperience: A nurse’s experience level also influences the intent to leave. Experience is also linked to other contributing factors such as burnout and job dissatisfaction. For instance, one study observed that burnout, work dissatisfaction and low quality of care were rather high across hospitals where 50% of the nursing workforce was relatively inexperienced (i.e., less than 10 years’ experience) compared to hospitals that have a 20% inexperienced workforce [34].

Job Location: The highest rate of job resignations occurs in Tokyo [35]. This may be due to higher professional mobility among nurses in Tokyo. Since only one study has observed this phenomenon, further research is needed to assess reasons for why nurses are leaving the profession altogether within major metropolitan areas in Japan. Poor preparation for job expectations: Another factor contributing to nurses leaving the profession is their lack of preparation for their job. When a nurse graduate is not well prepared for the profession, concerns arise, which can ultimately lead to the desire to leave [36].

Health and Well-Being: An individual’s mental, physical, and/ or general health may also impact the intent to leave a job and/or profession. In an analysis of newly graduated nurses, a study found that one’s own subjective health status (e.g. psychological distress or cumulative fatigue) significantly predicted the intention to leave, independent of demographic variables, stress or nursing skills [37]. Specifically, a lack of sleep has been identified as significantly predicting higher turnover [38].

Work/Life Balance: The ability to balance life and work also appears to be valued by nurses and may be impacting a desire to leave the profession. In particular, nurses born from 1960 to 1974 place a premium on the balance between their personal and professional life [39]. An imbalance may, therefore, contribute to nurses’ decisions to move to another line of work .

Capacity to Change: When there is a match between the importance nurses place on being able to challenge current clinical practices and actual opportunities to do so, intentions to leave diminish; however, when there is a mismatch, intentions to quit strengthen.

Socio-Cultural Factors
Lack of Co-Operation and Teamwork: A lack of co-operation and/or teamwork has been highlighted in several studies as impacting nurses’ intent to leave and turnover. Newly graduated nurses, for instance, highly value the level of support they receive from colleagues and supervisors. Nearly 10% of newly graduated nurses indicate a desire to leave nursing. Critical to this decision is whether nurses receive adequate social support from colleagues and supervisors. Organisational support can reduce burnout and contribute to job satisfaction, thus increasing commitment to the job and profession as a whole. Similarly, colleagues and supervisors play a critical role in nurse turnover. For instance, one study found that among hospitals with fewer than 500 beds, managerial and co-worker support significantly determined nurses’ intent to leave. Those nurses also stated that management styles and attitudes contributed to their intent to leave. Social support from peers, through a strong and interpersonal work ethic, was also highlighted as reducing the intent to leave.

Interpersonal Communication: Studies have also shown that difficulties in interpersonal communication between nurses of different ages can result in disputes. Intergenerational factors impact nurse turnover and play a role in understanding motivations behind turnover and developing an improved work environment for all nurses. Another study also suggests that poor cooperation among nurses affects nurse turnover. In excess of 50% of nurses in one study indicated that cooperation at work between nurses and doctors was either lacking or non-existent. Furthermore, ineffective cooperation and communication between nurses and/or conflict with supervisors is related to burnout. Together, these issues can contribute to nurses’ intent to leave and turnover. Finally, another dynamic to interpersonal relationships is gender differences and/or conservative attitudes, which further impact professional collegiality.

Gender Roles: In Japan, as in other countries, women have traditionally dominated the nursing profession. Perceptions of (and actual) gender roles impact the intent to leave and nursing turnover. For instance, conservatism within the health profession has been highlighted as more negatively impacting women in terms of burnout relative to men. Health professionals with patriarchal attitudes treat women nurses as subservient, resulting in added stress and fatigue. These rigid gender roles can be key to women leaving the nursing profession.

Organizational Factors
Remuneration: Actual remuneration, and a lack of transparency regarding remuneration reviews, may also be impacting turnover among nurses. In one study, nurses reported being dissatisfied with their salary and poor implementation of policies necessary to facilitate fair salary increases. Remuneration appears to be important based on historical factors. For instance, among individuals born after 1960, remuneration was more important relative to those born between 1946 and 1959. This could result from a lack of recognition or autonomy often perceived among nurses born between 1960 and 1974, which could perhaps be alleviated through fair salary compensation.

Health Facility Policies and Principles: Poor health facilities and inadequate hospital principles can contribute to job dissatisfaction among nurses, which can impact one’s intent to leave. The more a hospital is lacking in principles, the more likely nurses will be dissatisfied with their jobs and plan to leave the profession.

Commitment to an Organization: Another study identified that strong commitment to an organization positively impacted nurses’ job satisfaction, which led to a reduction in desires to leave. However, a lack of organizational commitment increased the intent to leave.

Work Environment: In one study, work environment had a relatively minor effect on the intent to leave. The types of work environment issues identified as influencing one’s intent to leave include the size and design of an individual’s workspace. Attraction to other jobs and/or professions may also contribute to leave intentions and turnover among nurses. In particular, nurses may find that they are attracted to a similar job to that of their colleagues either due to a better work environment or because the job is more suitable. This could mean that a nurse may pursue further education and training in another profession to obtain a more desirable career.

Clinical Challenges: One study identified a lack or excess of clinical challenges as potentially affecting intentions to leave. When nurses feel they are not adequately challenged at work, they are more likely to be disillusioned with their roles, which can lead to a desire to leave. On the other hand, excessive challenges can place undue stress on nurses, leading to job dissatisfaction and the desire to seek work elsewhere.

Professional Development: The greater the opportunity for professional development in the workplace, the less likely nurses plan to leave their job, especially among younger, less experienced nurses. New graduates tend to value organizations that contribute to their career development and are less likely to be dissatisfied with their job if they grow into their role. Thus, professional development opportunities can help reduce job dissatisfaction and foster organizational commitment.

Job Security: Actual and perceived job security also impacts one’s desire to leave a job. One study found that the more secure a nurse felt about his or her job, the more likely he or she was satisfied with the job and willing to stay with the organization. The value placed on job security, however, is generation dependent, with nurses born after 1960 valuing job security more than nurses born between 1946 and 1959.

Poor Quality of Care: Deteriorating quality of care in an organization, such as a hospital, is associated with intentions to leave and nursing turnover. For instance, in one study, nurses in poorly staffed hospitals were 75% more likely to report poor or fair quality care than nurses in better staffed hospitals. Improvements to care quality may therefore positively reduce turnover rates.

Workload: In one study, both the amount and type of work performed affected one’s intent to leave. Excessive levels of work and/or uninteresting or unchallenging work may lead to job dissatisfaction, which facilitates a desire to seek alternative employment.

Job Dissatisfaction and Burnout: Together, job dissatisfaction and burnout contribute to nurses’ intentions to leave. More than 50% of young nurses in one study were dissatisfied with their jobs. Another study also identified job satisfaction as a major contributor to nurses’ intent to leave. Conversely, one study observed only a minor correlation between job dissatisfaction and nurses’ intent to leave. Burnout and emotional exhaustion have also been identified in several studies as significantly contributing to job/professional resignation. For instance, one study concluded that emotional exhaustion affected over 50% of nurses surveyed [29], particularly those who were young and inexperienced. Similar results have also been highlighted in other studies. Graduate nurses, in particular, face great stress during their first year of employment. Here, nurses confront a steep learning curve. At the same time, turmoil and surprises are realities of their practice. In another study of newly graduated nurses, burnout was a leading cause of resignation toward the latter stages of employment.
Burnout and job dissatisfaction are related; together, they influence nurses’ intentions to leave the profession. Psychological distress and cumulative fatigue impact nurses’ intent to leave. Burnout can also influence several factors related to turnover, including interpersonal conflicts, skill mismatches and excessive workload. Likewise, a lack of cooperation among nurses and other health professionals within hospital environments leads to burnout and job dissatisfaction, which can significantly impact turnover.

Discussion
Interactions between Contributing Factors
No single factor, on its own, fully explains the shortage of nurses in Japan. Nurses quit their job and/or leave the profession for various reasons. Obtaining a comprehensive understanding of the motives for nurses leaving their jobs is inevitably complex. The context and circumstances surrounding each individual nurse will impact his or her decision to stay in a job and/or overall profession. The present analysis observed that intentions to leave and turnover are inextricably linked to various factors, which all contribute to the nursing shortage in Japan. For instance, inexperience, burnout, and job dissatisfaction are all linked to the delivery of poor healthcare. Specifically, burnout and work engagement are strongly related to both job and career satisfaction, as well as intentions to leave. Moreover, it appears that nurses who work in inadequately staffed units often express job dissatisfaction, stress, and burnout, which prompt them to seek new employment. Thus, future studies should be carried out to explore the significance of these factors in relation to nursing turnover in Japan.

Burnout is consistently associated with nurses’ intentions to leave their profession within and across European countries. Low staff to patient ratios and poor working relationships with physicians are linked to burnout. Unsatisfactory nurse-physician relationships, leadership, a lack of participation in hospital affairs, older age, male gender and part-time positions seem relevant at a global level, but results from studies are highly variable within individual countries, suggesting a need to specifically investigate these factors in relation to a Japanese context. The interactions between different personal, socio-cultural, organizational, and other factors are likely impacting nurses’ desires to leave the profession and turnover in a manner that is both unpredictable and difficult to quantify. Moreover, causes for nurses’ resignations may vary across time, depending on the direction of a particular nurse’s career.

Further research needs to be conducted as to address the varying factors affecting nurses’ decisions to resign from their jobs and pursue other careers. One area of focus could be the impact of workload on a nurse’s intent to leave. Too few studies have considered the interaction between workload and intent to leave. Thus, factors impacting nurses’ decision-making processes need to be carefully studied and understood by hospital employers and managers in order to address such nursing shortages. Another issue requiring further research is an investigation into the types of professions nurses pursue after leaving nursing and the reasons for choosing alternative careers. The specific job/career characteristics among alternative options should be compared to the benefits and limitations of nursing so as to gain further insight into the motivation’s nurses have for such alternative pursuits.

Strategies for Addressing Intent to Leave/Turnover
Considering that so many different factors contribute to intent to leave and turnover among nurses, it is inevitable that various strategies will need to be implemented to address nurse shortages resulting from high turnover. The study suggests that health and well-being courses designed to improve positive thinking for nurses may contribute to reducing their work-related stress and burnout. Acknowledging the efforts and contributions of nurses to the profession, career development and collegial approaches to management are also likely to have a significant positive influence on the intention to leave, and reduce turnover. Morale among nurses may be promoted by improving the relations between nurses and physicians. Physicians could be trained in acknowledging the efforts and contributions of nurses to the health profession. All participants in the delivery of quality health care need to be recognized by the system, to make it work more effectively. Managerial development too may lower turnover among nurses, particularly new graduates and less experienced nurses. Sound relations between nurses and their peers can also effectively reduce negative influences on nurse turnover.

Career progression and professional development may also have an impact. Training of younger inexperienced nurses may reduce the level of turnover in the profession (Lee, et al., 2009). Training of younger inexperienced nurses not only alleviates burnout among young nurses, but it also contributes to an improvement in interpersonal relations within hospitals. Education on understanding gender and intergenerational differences may also contribute to reducing nurse turnover and improving nurses’ work environments (Takase, et al., 2009). Further, to reduce the exit of women from the nursing profession, strategies need to be developed to address burnout and work/life balance. Practical work experience, career development and/or educational programmers (for example, gender studies) may assist.

Recommendations for Future Research
A number of studies have been undertaken which show that the factors affecting nursing turnover in Japan encompass personal, socio-cultural and organizational elements. Therefore, longitudinal studies are needed which explore more deeply and monitor these factors that are not static but changing over time. Furthermore, it would be helpful to carry out qualitative inquires examining the impact of nursing turnover on the well-being and productivity of those that remain in the workforce. In order to better understand how changing societal and work conditions over time lead nurses to leave a post or the profession, researchers might employ narrative methods to collect and analyses their stories. In general, more research is warranted in order to better understand turnover behavior and how turnover within the skilled nursing workforce impacts the capacity of the health sector to respond to the increasing demands for health care.

Conclusion
Generalizations about each particular nurse’s decision to leave their job or the profession are difficult to make. The interplay between various subjective and objective factors lead each particular nurse to decide to leave their job or the profession. The manner in which a nurse describes their decision to leave too may have a bearing on the analysis. All this makes it difficult to assess each separate factor contributing towards nurses’ intent to leave. However, certain common threads have been identified in the literature both in Japan and more generally internationally. These include interpersonal relations, skills mismatch and poor quality of care to name a few. Other factors, however, also contribute. Ultimately, each factor may have a varying degree of influence to each individual’s decision to resign. When many individuals decide to leave a profession though, an analysis of the factors determining the decision need to be considered - particularly when the profession is significant to society and the health and well-being of its members. Delivery of quality health care becomes critical as it becomes more difficult to attract and retain nurses. High nurse turnover can be costly and detrimental to society, imposing a heavy burden on the delivery of health care. Attempting to find a solution to the supply factors contributing to nurses leaving the profession is not only a worthwhile pursuit for the profession, but more critically for society generally. Nurses must feel valued in their job and must feel like they are contributing. Only then will the quality of health care in society improve and Japan’s and other nations’ welfare progress and advance.

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