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Saif A Muhsin, David Wojciechowski Nephrology Division and Transplant Center, Massachusetts General Hospital, Boston, MA, USACorrespondence: David WojciechowskiUT Southwestern Medical Center, Dallas, TX USATel +1 214 645 7846Email david.wojciechowski@utsouthwestern.eduAbstract: Since its discovery in 1971, BK Polyomavirus infection has been increasingly recognized, especially since the introduction of more effective immunosuppressive medications in the early 1990s. BK virus is believed to have a high seroprevalence in healthy individuals, entering a latent phase in the genitourinary that follows the primary infection. Reactivation may occur in immunocompromised hosts, with significant effects seen especially in kidney and hematopoietic stem cell transplant recipients. Screening methods have been developed and are implemented as early detection may allow for the prevention of irreversible tissue damage. Reduction of immunosuppression remains the cornerstone of therapy for BKV infection, and adjunctive therapies have shown variable results. Newer cellular-based therapeutics might provide a more targeted treatment for BKV infection but are still in need of more randomized human studies.Keywords: kidney transplantation, BK polyomavirus, immunosuppression

The study aimed to determine the optimal pulverisation index of soil for disk harrow by modelling. A mathematical model was developed using a Design-Expert software and response surface methodology. Experiments were carried out in silty loamy soil with three different levels of soil moisture content of 9.25%, 17.56%, and 22.32%, operating depths of 10 cm, 15 cm, and 20 cm, and operating speeds of 3.17, 4.85, and 5.47 km·h-1. The quadratic model proposed by the Design-Expert software was statistically significant (P

Lead toxicity elicits neurological damage which is a well-known disorder that has been considered to be a major cause for multiple condition such as behavioral defect; mental retardation; and nerve insufficient activity. This research is designed to estimate potential protective effect of vinpocetine on neurotoxicity stimulated by lead acetate in rats. Eighteen adult rats of both sexes were randomly enrolled into three groups. Each group includes 6 rats as followings: Group I- Rats were given 0.3ml normal saline solution orally; then intraperitoneal injection of 100μl of the normal saline was given 1h later; this group was considered as control. Group II- Rats were given an intraperitoneal injection of 20mg/kg lead acetate for 5 days. Group III- Rats were orally given 3mg/kg vinpocetine, which was given 1hr before [(the IP injection of Pb every 24 hours at a dose of 20mg/kg) for 5 days and continued for 10 days]. On 11th day of the study, the brain of each animal has been surgically cut-out to make homogenate preparation to estimate tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-10 (IL-10) levels. Lead significantly elevated TNF-α and IL-1beta; while, it significantly decreased IL-10 levels. Vinpocetine significantly minimized IL-1beta and TNF-α; furthermore, vinpocetine significantly raise IL-10 levels at (P

Abstract Iraqi propolis (PR) have powerful antioxidants, free radical scavenger and anti-inflammatory constituents makes it to have a protective effect on renal function. The aim of this study is to evaluate the possible protective effect of Iraqi propolis (PR) on renal toxicity induced by Carbimazole (CB) and levothyroxine (TR) in rats. Forty-two adult female albino rats randomized into six groups: control, PR, CB, TR, PR + CB and PR +TR. Rats orally treated by gavage for six weeks. Haematological and histopathological analyses performed. A significant increase in hemoglobin percentage, RBC count and Haematocrit percentage after exposure to PR + CB and PR + TR combinations compared to control. CB dose of 0.01mg /g for six weeks causes renal damage in female rats and TR dose of 0.1µg/g for six weeks causes renal degenerative effects. Rats treated with PR+TR show normal appearance in kidney tissue, glomeruli and renal tubules compared to thyroxin group alone. In addition, PR+ CB treatment show more improvement in renal tissue, normal glomeruli and renal tubules compared to CB alone. It is concluded that PR combination with CB or TR might have an effect on the blood, further studies needed to confirm this effect on human to be used for anemia accompanied thyroid disruptions. In addition, further studies needed to confirm renal protective effect on human to be used for this effect.

أما المحور الثاني فقد تناول دور البنك الصناعي في التنمية والاستثمار الصناعي، وهذا المحور بدوره انقسم إلى فرعين، تناول الأول القروض التي قدمها البنك خلال فترة البحث، والثاني أبرز دور البنك الصناعي. البنك الصناعي في تنمية القطاع الصناعي المختلط والذي لقي دعما كبيرا منه

Amaç: Ameloblastoma agresif, lokal invaziv aynı zamanda asemptomatik ve yavaş büyüyen benign bir epitelyal tümördür. Radyografik olarak lezyon görünümü değişkendir ve çeşitli kist ve tümörler ile karışabilir. Bu çalışmanın amacı, histopatolojik olarak ameloblastoma tanısı konulan 25 vakanın demografik ve radyografik özelliklerinin dağılımının belirlenmesidir.Gereç ve Yöntemler: Hastaların yaşı, cinsiyeti, lezyonların yeri, radyografik özellikleri ve histopatolojik özellikleri açısından veriler analiz edildi.Bulgular: Ortalama yaş erkeklerde 34.5 ± 17.9, kadınlarda 44.5 ± 23.5 ve erkek kadın oranı 1.27 : 1 bulundu. Histolojik olarak 13 vaka solid/multikistik, 10 vaka unikistik, iki vaka desmoplastik tipteydi. 24 (% 96) vaka mandibulada, 1 (% 4) vaka maksillada göründü. 16 (% 64) lezyonda hem bukkal hem lingual kortikal kemikte ekspansiyon izlendi. Lezyonların 14’ü (% 56) uniloküler, 11’i (% 44) multiloküler görünümdeydi. Multiloküler lezyonların ikisi (% 8) örümcek ağı, sekizi (% 32) sabun köpüğü, biri (% 4) bal peteği görünümündeydi. Sadece bir (% 4) lezyonun sınırları kötü, diğer hepsi (% 96) iyi tanımlıydı. 16 (% 72) lezyonun sınırları düzgün, dokuzu (% 36) deniz tarağı şekildeydi.Sonuç: Ameloblastomalar genel olarak kadın hastalarda erkeklere göre daha geç yaşlarda ortaya çıkar. Bu çalışmadaki ameloblastomaların radyografik olarak baskın özellikleri sırasıyla iyi tanımlanmış kortikal sınır, bukkal ve lingual kortikal kemikte ekspansiyon, düzgün kenar sınırları, unilokuler radyolusensi, multilokuler radyolusensi, kök rezorpsiyonu, deniz tarağı şeklinde kenar sınırları, sabun köpüğü görünümü ve dişlerde yer değişikliğidir.ANAHTAR KELİMELER Ameloblastoma, Konik Işınlı Bilgisayarlı Tomografi, Histopatoloji, Panoramik Radyografi

Çimento ve puzolanlar bu günün hızlı gelişen yapı sektöründe yaygın olarak kullanılmaktadır. Betonarme yapı tasarımında dayanımın yanında dayanıklılık da çağımızda giderek önem kazanmaktadır. Zeolit gibi puzolanik malzemeler, ekonomik ve ekolojik faktörler nedeniyle çimento ve beton sektöründe yaygın olarak kullanılmaktadır. Çalışmada, Türkiye'de oldukça zengin kaynaklara sahip olan zeolitin ikamesi ile üretilen betonların fiziksel ve mekanik özellikleri belirlenmeye çalışılmıştır. Bu çalışma, sodyum klorür (NaCl) etkisi altındaki zeolit ikameli betonların davranışını araştırmak için yapılmıştır. Bu amaçla zeolit sırasıyla, %0, %10 ve %20 oranlarında Portland çimentosu yerine ikame edilerek 3 farklı çimento elde edilmiştir. Her beton grubu için bu çimentolarla üretilmiş toplam 54 adet 15x15x15 cm ebadında küp örnekler üretilmiştir. Örnekler hazırlanırken çökme miktarı 7 ile 10 cm arasında olacak şekilde beton karışım dizaynı yapılmıştır. Üretilen sertleşmiş beton örnekleri üzerinde birim ağırlık, su emme, görünür boşluk oranı, ultrases geçiş hızı, kapiler su emme, yarmada çekme dayanımı ve basınç dayanımı deneyleri yapılmıştır. Sertleşmiş beton deneyleri, üç farklı beton türü üzerinde, 28 gün 23±2 oC suda, daha sonra NaCl ve beton yaşı faktörünün iki düzeyinde (56 ve 90 gün) kür edilen beton örnekleri üzerinde gerçekleştirilmiştir. Sonuç olarak, sertleşmiş beton örneklerinin basınç dayanımı, yarmada çekme dayanımı, kapilerite katsayısı, ultrases geçiş hızı, görünür boşluk oranı, su emme oranı ve birim hacim ağırlık deneylerinin tümünün birbiri ile uyumlu olduğu belirlenmiştir.

Background: Chronic wasting disease (CWD) is a fatal transmissible spongiform encephalopathy in cervids. The disease is caused by a pathogenic prion, namely PrP Sc . Currently, diagnosis of CWD relies on IHC detection of PrP Sc in the obex or retropharyngeal lymph nodes (RPLN) or ELISA screening of obex and RPLN followed by IHC confirmation of positive results. In this study, we assessed the performance characteristics of two immunoassays: CWD Ag-ELISA and TeSeE ELISA, RT-QuIC, and MEMS biosensor via testing 30 CWD + and 30 CWD- white-tailed deer RPLN samples., Results: Both CWD Ag-ELISA and TeSeE ELISA correctly identified all CWD + and CWD- samples. A greater intra-assay coefficient of variation (CV) in S/P ratios was observed for the TeSeE ELISA (16.52%), compared to CWD Ag-ELISA (9.49%). However, the high CV did not affect the qualitative results of triplicate assays when the corresponding manufacturer's cutoff was used. The MEMS biosensor not only correctly identified all CWD + and CWD- RPLN samples, but also demonstrated a 100% detection rate for all CWD + samples at dilutions from 10 - 0 to 10 - 3 . Evaluation of RT-QuIC indicated that the rate of false negative reactions decreased from 21.98% at 10 - 2 dilution to 0% at 10 - 4 and 10 - 5 dilutions; and the rate of false positive reactions reduced from 56.42% at 10 - 2 dilution to 8.89% and 2.22% at 10 - 4 and 10 - 5 dilutions, respectively. Based on a stringent threshold of 2 x the first 10 fluorescent readings of each well and a final cutoff of 2/3 positive reactions for each sample, RT-QuIC correctly identified all positive and negative samples at 10 - 4 and 10 - 5 dilutions. Both MEMS biosensor and RT-QuIC achieved 100% sensitivity and 100% specificity under the experimental conditions described in this study., Conclusions: The two immunoassays (CWD Ag-ELISA and TeSeE ELISA) performed comparably on white-tailed deer RPLN samples. MEMS biosensor is a reliable portable tool for CWD diagnosis and RT-QuIC can be used for routine testing of CWD if appropriate testing parameters and interpretive criteria are applied., Competing Interests: Declarations Ethics approval and consent to participate This research did not involve live animals. Retropharyngeal lymph nodes were collected from hunter-harvested dead deer by MDC as part of Misosuri CWD surveillance program. Sample collection and submission protocols were reviewed and approved by MDC Science Committee. Comparative study protocol was approved by the University of Missouri Institutional Biosafety Committee (protocol number: 11721 2.2). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Helio Tedesco Silva is supported by research grants from Novartis, Natera, and Merck & Co. through his institution. He received honoraria for lectures from Takeda, EMS, CardeDx and Natera. Additionally, he received monetary support from Takeda to attend meetings. A. Bernard Collins receives royalties from Elsevier. He also reports receiving honoraria from Euroimmun. Nikhil Agrawal has employment stocks and options from CareDx Inc. He is also currently employed by CareDx Inc. Ayman Al Jurdi is supported by AstraZeneca through grant funding for an investigator-initiated study related to another project. Roberto C. Manfro served on the data safety monitoring board of Instituto Butanatan in São Paulo, Brazil, for which he did not receive any payments. Giorgia Comai received honoraria from Novartis, Hansa Biopharma, and Alexion. Additionally, she is a part of the Biotest Advisory Board, for which she receives payments. Paolo Cravedi is supported by the NIH award R01 DK123234 and has received research funding from Chinook Therapeutics. Leonardo V. Riella is supported by the NIH award R01 AI143887 and has received research funding for unrelated projects from Visterra, Caredx, AstraZeneca, Natera, and Bristol-Meyers-Squibb. All remaining authors have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This virtual study was designed to evaluate the stress-deformation of a metal fixed partial dentures (FPDs) pontic under different loads using two different connectors. The STL file was generated for a RPD of two implant-supported restorations. The Co-Cr metal substructure was designed with two types of connector design. The pontic is connected to implant-supported crowns with square and round shape connectors. This study was designed for a cementless-retained implant-supported FPD. Finite element modeling (FEM) is used to assess the stress and deformation of the pontic within a metal substructure as the FEM might provide virtual values that could have laboratory and clinical relevance. The Co-Cr alloy mechanical properties like the Poisson ratio and modulus of elasticity were based on the parameters of the three-dimensional structure additive method. Nonparametric analyses (Mann-Whitney U test) was used. The use of square or round connectors often resulted in non-significant changes in stress, and deformation under either three or each loaded point on the occlusal surface of a pontic (P > 0.05). However, the deformation revealed distinct variations between loads of the three points compared to each loaded point (P ≤ 0.05). According to this study data, the pontic occlusal surface appears to be the same in stress and deformation under different loads depending on whether square or round connectors are used. While at the same connector designs, the pontic occlusal surface deformed significantly at three loaded points than it did at each point.

The lack of enough diagnostic capacity to detect severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has been one of the major challenges in the control the 2019 COVID pandemic; this led to significant delay in prompt treatment of COVID-19 patients or accurately estimate disease situation. Current methods for the diagnosis of SARS-COV-2 infection on clinical specimens (e.g. nasal swabs) include polymerase chain reaction (PCR) based methods, such as real-time reverse transcription (rRT) PCR, real-time reverse transcription loop-mediated isothermal amplification (rRT-LAMP), and immunoassay based methods, such as rapid antigen test (RAT). These conventional PCR methods excel in sensitivity and specificity but require a laboratory setting and typically take up to 6 h to obtain the results whereas RAT has a low sensitivity (typically at least 3000 TCID50/ml) although with the results with 15 min. We have developed a robust micro-electro-mechanical system (MEMS) based impedance biosensor fit for rapid and accurate detection of SARS-COV-2 of clinical samples in the field with minimal training. The biosensor consisted of three regions that enabled concentrating, trapping, and sensing the virus present in low quantities with high selectivity and sensitivity in 40 min using an electrode coated with a specific SARS-COV-2 antibody cross-linker mixture. Changes in the impedance value due to the binding of the SARS-COV-2 antigen to the antibody will indicate positive or negative result. The testing results showed that the biosensor's limit of detection (LoD) for detection of inactivated SARS-COV-2 antigen in phosphate buffer saline (PBS) was as low as 50 TCID50/ml. The biosensor specificity was confirmed using the influenza virus while the selectivity was confirmed using influenza polyclonal sera. Overall, the results showed that the biosensor is able to detect SARS-COV-2 in clinical samples (swabs) in 40 min with a sensitivity of 26 TCID50/ml., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Cervids are affected by a neurologic disease that is always fatal to individuals and has population effects. This disease is called chronic wasting disease (CWD) and is caused by a misfolded prion protein. The disease is transmitted via contact with contaminated body fluids and tissue or exposure to the environment, such as drinking water or food. Current CWD diagnosis depends on ELISA screening of cervid lymph nodes and subsequent immunohistochemistry (IHC) confirmation of ELISA-positive results. The disease has proven to be difficult to control in part because of sensitivity and specificity issues with the current test regimen. We have investigated an accurate, rapid, and low-cost microfluidic microelectromechanical system (MEMS) biosensing device for the detection of CWD pathologic prions in retropharyngeal lymph nodes (RLNs), which is the current standard type of CWD diagnostic sample. The device consists of three novel regions for concentrating, trapping, and detecting the prion. The detection region includes an array of electrodes coated with a monoclonal antibody against pathologic prions. The experimental conditions were optimized using an engineered prion control antigen. Testing could be completed in less than 1 hour with high sensitivity and selectivity. The biosensor detected the engineered prion antigen at a 1:24 dilution, while ELISA detected the same antigen at a 1:8 dilution. The relative limit of detection (rLOD) of the biosensor was a 1:1000 dilution of a known strong positive RLN sample, whereas ELISA showed a rLOD of 1:100 dilution. Thus, the biosensor was 10 times more sensitive than ELISA, which is the currently approved CWD diagnostic test. The biosensor's specificity and selectivity were confirmed using known negative RPLN samples, a negative control antibody (monoclonal antibody against bovine coronavirus BCV), and two negative control antigens (bluetongue virus and Epizootic hemorrhagic disease virus). The biosensor's ability to detect pathogenic prions was verified by testing proteinase-digested positive RLN samples., Competing Interests: Conflict of interestThe authors declare no competing interests., (© Aerospace Information Research Institute, Chinese Academy of Sciences 2023.)

A microfluidic based biosensor was investigated for rapid and simultaneous detection of Salmonella, Legionella, and Escherichia coli O157:H7 in tap water and wastewater. The biosensor consisted of two sets of focusing electrodes connected in parallel and three sets of interdigitated electrodes (IDE) arrays. The electrodes enabled the biosensor to concentrate and detect bacteria at both low and high concentrations. The focusing region was designed with vertical metal sidewall pairs and multiple tilted thin-film finger pairs to generate positive dielectrophoresis (p-DEP) to force the bacteria moving toward the microchannel centerline. As a result, the bacterial pathogens were highly concentrated when they reached the detection electrode arrays. The detection IDE arrays were coated with three different antibodies against the target bacterial pathogens and a cross-linker to enhance the binding of antibodies to the detection electrode. As the binding of bacterial pathogen to its specific antibodies took place, the impedance value changed. The results demonstrated that the biosensors were capable of detecting Salmonella, Legionella, and E. coli 0157:H7 simultaneously with a detection limit of 3 bacterial cells/ml in 30 - 40 min., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Colchicine is commonly prescribed for treatment of inflammatory conditions but has a narrow therapeutic window and dangerous toxicity profile. Here we describe a case of survival after massive unintentional colchicine overdose treated with plasmapheresis and renal replacement therapy. A 37 year old male with history of pericarditis presented to the Emergency Department with a chief complaint of nausea, vomiting, and diarrhea after unintentionally ingesting 36 mg of colchicine 17 h prior to arrival. An initial colchicine concentration resulted at 5.1 ng/mL (30 h post-ingestion) and peaked at 12 ng/mL (40 h post-ingestion). He was treated with continuous kidney replacement therapy (CKRT) beginning on his first day of hospitalization and with plasmapheresis on hospital days two through four. The patient's course was complicated by multiorgan failure including coagulopathy, respiratory failure, neuropathy, renal failure, pancytopenia, and heart failure. He was discharged to inpatient rehabilitation on hospital day 24. On clinical follow up four months after discharge the patient was found to have no significant persistent morbidity related to colchicine overdose., Competing Interests: Disclosure statement No potential conflict of interest was reported by the authors.

Background and Objectives: In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small., Design, Setting, Participants, & Measurements: We performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 "The Post-Transplant Glomerular Disease" study centers in Europe, North America, and South America., Results: Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donor-specific antibodies (hazard ratio, 2.59; 95% confidence interval, 1.09 to 6.19). After kidney transplantation, development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence., Conclusions: In our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss., (Copyright © 2021 by the American Society of Nephrology.)

Solid organ transplantation is a lifesaving therapy for patients with end-organ disease. Current immunosuppression protocols are not designed to target antigen-specific alloimmunity and are uncapable of preventing chronic allograft injury. As myeloid-derived suppressor cells (MDSCs) are potent immunoregulatory cells, we tested whether donor-derived MDSCs can protect heart transplant allografts in an antigen-specific manner. C57BL/6 (H2K b , I-A b ) recipients pre-treated with BALB/c MDSCs were transplanted with either donor-type (BALB/c, H2K d , I-A d ) or third-party (C3H, H2K k , I-A k ) cardiac grafts. Spleens and allografts from C57BL/6 recipients were harvested for immune phenotyping, transcriptomic profiling and functional assays. Single injection of donor-derived MDSCs significantly prolonged the fully MHC mismatched allogeneic cardiac graft survival in a donor-specific fashion. Transcriptomic analysis of allografts harvested from donor-derived MDSCs treated recipients showed down-regulated proinflammatory cytokines. Immune phenotyping showed that the donor MDSCs administration suppressed effector T cells in recipients. Interestingly, significant increase in recipient endogenous CD11b + Gr1 + MDSC population was observed in the group treated with donor-derived MDSCs compared to the control groups. Depletion of this endogenous MDSCs with anti-Gr1 antibody reversed donor MDSCs-mediated allograft protection. Furthermore, we observed that the allogeneic mixed lymphocytes reaction was suppressed in the presence of CD11b + Gr1 + MDSCs in a donor-specific manner. Donor-derived MDSCs prolong cardiac allograft survival in a donor-specific manner via induction of recipient's endogenous MDSCs.

Induction of longstanding immunologic tolerance is essential for survival of transplanted organs and tissues. Despite recent advances in immunosuppression protocols, allograft damage inflicted by antibody specific for donor organs continues to represent a major obstacle to graft survival. Here we report that activation of regulatory CD8 T cells (CD8 Treg) that recognize the Qa-1 class Ib major histocompatibility complex (MHC), a mouse homolog of human leukocyte antigen-E (HLA-E), inhibits antibody-mediated immune rejection of heart allografts. We analyzed this response using a mouse model that harbors a point mutation in the class Ib MHC molecule Qa-1, which disrupts Qa-1 binding to the T cell receptor (TCR)-CD8 complex and impairs the CD8 Treg response. Despite administration of cytotoxic T lymphocyte antigen 4 (CTLA-4) immunoglobulin (Ig), Qa-1 mutant mice developed robust donor-specific antibody responses and accelerated heart graft rejection. We show that these allo-antibody responses reflect diminished Qa-1-restricted CD8 Treg-mediated suppression of host follicular helper T cell-dependent antibody production. These findings underscore the critical contribution of this Qa-1/HLA-E-dependent regulatory pathway to maintenance of transplanted organs and suggest therapeutic approaches to ameliorate allograft rejection., Competing Interests: The authors declare no competing interest.

Background and Objectives: FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients., Design, Setting, Participants, & Measurements: The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors., Results: Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0-8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m 2 ; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival., Conclusions: Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases., (Copyright © 2020 by the American Society of Nephrology.)

Purpose: To optimize the gypsum mold temperatures for pressed PEEK, and to estimate the impact, tensile strength and flexural properties of pressed and milled PEEK. Where appropriate, these properties were compared with those of PMMA., Materials and Methods: Since the mold temperature could affect the properties of the injected parts, the temperature of 20 gypsum specimens was monitored using the multi-thermocouple system (n = 5). A total of 210 specimens were prepared for mechanical tests according to the ISO standard for denture base polymer (n = 10). The Izod impact, tensile strength, and flexural behavior were assessed. PEEK-OptimaNI1 (PEEK-pressed) was tested after processing via the pressing method at4 different mold temperatures. Machining PEEK-Juvora (PEEK-milled) specimens were prepared using the CAD-CAM production method. Data were analyzed via one-way ANOVA performed at a confidence level of 95% and a significant P-value of (P ≤ 0.05)., Results: In comparison to the furnace temperature more heat was required to preheat the gypsum mold up to 100, 150, 175 and 200 °C for pressing purposes. The highest impact strength was 5.7 kJ/m 2 for PEEK-pressed at 100 °C mold temperature and 4 kJ/m 2 for PEEK-milled. The latter had a higher tensile strength of 118 MPa. The best result for PEEK-pressed was 97 MPa at 200 °C mold temperature. Under a 4-point bending test, Young's modulus of PEEK-milled was 5591 MPa, while the highest for PEEK-pressed was 4936 MPa at 200 °C mold temperature., Conclusions: Compared to PMMA, given the superior mechanical properties of PEEK, it may become the material of choice for future use. Dentures constructed from PEEK polymer could well be routinely constructed in the near future.

Rationale: IgG4-related disease (IgG4-RD) is a multiorgan disease of unestablished prevalence that is characterized histopathologically by a dense lymphoplasmacytic infiltrate enriched with IgG4-expressing plasma cells and associated with storiform fibrosis. Tubulointerstitial nephritis (TIN) is the most common renal manifestation of IgG4-RD, but membranous nephropathy (MN) has also been described and often occurs in the context of concurrent TIN. Patients with IgG4-related MN have been characteristically negative for autoantibodies to the phospholipase A2 receptor (PLA2R)., Patient Concerns: A 45-year-old man presented with abdominal pain and lower extremity edema., Diagnosis: Histopathological evaluation of pancreas and liver biopsies established a diagnosis of IgG4-RD. Renal biopsy confirmed a diagnosis of PLA2R-associated MN without evidence of concurrent TIN., Interventions: The patient was treated with rituximab, a short course of low-dose, oral cyclophosphamide, and a rapid glucocorticoid taper., Outcomes: The patient achieved remission of MN after 8 months of therapy and maintained remission of IgG4-RD., Lessons: PLA2R-associated MN may be a rare manifestation of IgG4-RD. Systematic evaluation of larger cohorts of IgG4-RD patients for the presence of PLA2R autoantibodies and the investigation of PLA2R-associated MN cohorts for evidence of IgG4-RD would facilitate the understanding of the nature of the relationship between these observations.

Background: The ePartogram is a tablet-based application developed to improve care for women in labor by addressing documented challenges in partograph use. The application is designed to provide real-time decision support, improve data entry, and increase access to information for appropriate labor management. This study's primary objective was to evaluate the feasibility and acceptability of ePartogram use in resource-constrained clinical settings., Methods: The ePartogram was introduced at three facilities in Zanzibar, Tanzania. Following 3 days of training, skilled birth attendants (SBAs) were observed for 2 weeks using the ePartogram to monitor laboring women. During each observed shift, data collectors used a structured observation form to document SBA comfort, confidence, and ability to use the ePartogram. Results were analyzed by shift. Short interviews, conducted with SBAs (n = 82) after each of their first five ePartogram-monitored labors, detected differences over time. After the observation period, in-depth interviews were conducted (n = 15). A thematic analysis of interview transcripts was completed., Results: Observations of 23 SBAs using the ePartogram to monitor 103 women over 84 shifts showed that the majority of SBAs (87-91%) completed each of four fundamental ePartogram tasks-registering a client, entering first and subsequent measurements, and navigating between screens-with ease or increasing ease on their first shift; this increased to 100% by the fifth shift. Nearly all SBAs (93%) demonstrated confidence and all SBAs demonstrated comfort in using the ePartogram by the fifth shift. SBAs expressed positive impressions of the ePartogram and found it efficient and easy to use, beginning with first client use. SBAs noted the helpfulness of auditory reminders (indicating that measurements were due) and visual alerts (signaling abnormal measurements). SBAs expressed confidence in their ability to interpret and act on these reminders and alerts., Conclusions: It is feasible and acceptable for SBAs to use the ePartogram to support labor management and care. With structured training and support during initial use, SBAs quickly became competent and confident in ePartogram use. Qualitative findings revealed that SBAs felt the ePartogram improved timeliness of care and supported decision-making. These findings point to the ePartogram's potential to improve quality of care in resource-constrained labor and delivery settings.

Introduction: Remission induction in antineutrophil cytoplasmic autoantibody (ANCA) vasculitis may be complicated by slow response to treatment and toxicity from glucocorticoids. We describe outcomes with a novel remission induction regimen combining rituximab with a short course of low-dose, oral cyclophosphamide and an accelerated prednisone taper., Methods: Patients were included in this retrospective study if they had newly diagnosed or relapsing ANCA vasculitis with a Birmingham Vasculitis Activity Score for Wegener Granulomatosis (BVAS-WG) ≥3 and received a standardized remission induction regimen. The primary outcome was complete remission, defined as a BVAS-WG of 0 and a prednisone dose of ≤7.5 mg/d., Results: We identified 129 patients who met the inclusion criteria, 31% of whom also received plasma exchange (PLEX) for rapidly progressive glomerulonephritis (RPGN) or diffuse alveolar hemorrhage. Seventy percent of patients had myeloperoxidase (MPO)-ANCA and 9% had relapsing disease. Median time to complete remission was 4 months (interquartile range [IQR] 3.9-4.4), and by 5 months 84% of patients were in complete remission. Prednisone was tapered to discontinuation as tolerated, such that the median prednisone dose at 8 months was 0 mg/d (IQR 0-2.5). In patients with RPGN, proteinase 3-ANCA was associated with a greater increase in eGFR at 6 months compared with MPO-ANCA (16 vs. 5.6 ml/min per 1.73m 2 ; P  = 0.028). During the year following remission, 1 major relapse occurred over 122 patient-years. Serious infections occurred more frequently in patients receiving PLEX and were associated with increasing age and diffuse alveolar hemorrhage. Four deaths occurred, 3 of which were associated with serious infections., Conclusion: Combination therapy was efficacious, allowed for rapid tapering of high-dose glucocorticoids and was well tolerated.

Background: Although bonding to denture teeth after surface treatment with chemical agents is desirable, there is little information on the use of Visible Light Cure composite resin (VLC) as bonding denture materials., Objectives: To determine the effect of various surface treatments on shear bond strength between Visible Light Cure composite resin and the acrylic denture teeth interface., Methods: Forty cylindrical sticks of acrylic resin with denture teeth mounted atop were prepared. Various treatments were implemented upon the acrylic resin teeth surfaces. The samples were divided into four groups (n = 10). Light-cured composite resin (LC) was applied over all treated and untreated surfaces of tested groups. The shear bond was tested using a universal tensile testing apparatus with the knife-edge of a 0.8mm shear tester. Data were statistically analyzed using one-way ANOVA performed at a confidence level of 95% and significant P-value of (P ≤ 0.05)., Results: Analysis of variance (ANOVA) showed statistically significant difference (P < 0.05) between treated and untreated teeth surfaces. The treated surfaces exhibited various levels of bond strength depending on the type of treatment., Conclusion: Application of VLC bonding agent with prior treatment of methylmethacrylate (MMA) on the acrylic resin denture teeth resulted in maximum bond strength with composite resin.

Transforming growth factor-β (TGF-β) is generally considered as a central mediator of fibrotic diseases. Indeed, much focus has been placed on inhibiting TGF-β and its downstream targets as ideal therapeutic strategies. However, pharmacological blockade of TGF-β has not yet translated into successful therapy for humans, which may be due to pleiotropic effects of TGF-β signaling. Equally, TGF-β signaling as a protective response in kidney injury has been relatively underexplored. An emerging body of evidence from experimental kidney disease models indicates multifunctionality of TGF-β capable of inducing profibrotic and protective effects. This review discusses recent advances highlighting the diverse roles of TGF-β in promoting not only renal fibrosis but also protective responses of TGF-β signaling. We review, in particular, growing evidence that supports protective effects of TGF-β by mechanisms which include inhibiting inflammation and induction of autophagy. Additional detailed studies are required to fully understand the diverse mechanisms of TGF-β actions in renal fibrosis and inflammation that will likely direct toward effective antifibrotic therapies., (Copyright © 2016 the American Physiological Society.)

Hypernatremia is defined as a serum sodium level above 145 mmol/L. It is a frequently encountered electrolyte disturbance in the hospital setting, with an unappreciated high mortality. Understanding hypernatremia requires a comprehension of body fluid compartments, as well as concepts of the preservation of normal body water balance. The human body maintains a normal osmolality between 280 and 295 mOsm/kg via Arginine Vasopressin (AVP), thirst, and the renal response to AVP; dysfunction of all three of these factors can cause hypernatremia. We review new developments in the pathophysiology of hypernatremia, in addition to the differential diagnosis and management of this important electrolyte disorder., (Copyright © 2016. Published by Elsevier Ltd.)

Pulmonary embolism is a common, potentially fatal disease. Making the correct diagnosis early can significantly reduce mortality and morbidity. We report the first case of drenching night sweats as one of the presenting symptoms of submassive pulmonary embolism. One week after undergoing laparotomic sigmoidectomy for diverticulitis, our patient started to experience drenching night sweats and pleuritic back pain. CT identified bilateral main stem pulmonary artery emboli, and treatment was initiated with subcutaneous enoxaparin injections. Imaging and laboratory workup failed to reveal any other explanation for the night sweats. Patient was discharged on rivaroxaban, and he reported complete resolution of symptoms upon the 3-month follow-up visit and 9-month follow-up call. Based on our case we propose night sweats to be a potential presenting symptom of pulmonary embolism. Our observation can help make an earlier diagnosis of pulmonary embolism.

Objective: To describe the etiology, clinical presentation, management and outcome of liver abscess in adult patients admitted at Hamad general hospital, Qatar., Methods: A cross sectional study was conducted to involve all adult patients who sequentially encountered episodes of liver abscess during the period from January 1, 2009, to December 31, 2010. Blood cultures were drawn from all patients in the first 24 hours after admission. In addition, all patients had stool examinations and indirect Hemagglutination test for Entameba histolytica. Aspiration of abscess was done under CT guidance and aspirated pus was sent for gram stain and culture., Results: In total, 67 patients were admitted with liver abscess; 56 patients with pyogenic liver abscess and 11 with amebic liver abscess. There were 61 (91%) males and six (9%) females and their mean age was 47.4 ± 18.5 years. Fever, abdominal pain and vomiting were the commonest presenting features. Of the 56 pyogenic liver abscess patients, four discharged against medical advice and seven refused all invasive procedures and were treated with antibiotics for six weeks. The remaining 44 (79%) patients were treated with antibiotics and one or more invasive procedures, while one patient was treated surgically. The commonest organism isolated was Klebseilla pneumonia found in 21 patients (38%). The mean duration of hospitalization was 13.6 ± 8.1 days; the mean duration of antibiotic therapy was 34.7 ± 40.6 days, and one patient died. In contrast, all amebic liver abscess patients underwent ultrasound guided aspiration and showed good response to metronidazole treatment. Their mean duration of hospitalization was 7.7 ± 4.1 days, mean duration of therapy was 11.8 ± 2.1 days, and all patients were cured., Conclusion: Pyogenic liver abscess was more common than amebic liver abscess with Klebseilla pneumonia being the commonest organism. With good medical measures and early drainage of liver abscess, surgical intervention was unnecessary in almost all the cases.

Introduction: Amphotericin B (AmB) was first approved by the US Food and Drug Administration in 1959 with sodium deoxycholate (DAmB, Fungizone®). Extensive toxicities associated with the drug led to the development of lipid formulations of AmB, including liposomal amphotericin B (L-AmB, AmBisome®). Phase I studies as well as comparative Phase III clinical trials indicate that L-AmB is associated with less nephrotoxicity and reduced infusion-related toxicity. There is, however, no recent comprehensive review of the safety and tolerability of L-AmB., Areas Covered: This article reviews the safety, tolerability and the mechanisms of the major toxicities associated with L-AmB, including nephrotoxicity, infusion-related reactions (IRRs), anemia and thrombocytopenia, and hepatic abnormalities. The article further discusses the mechanism of action and pharmacokinetics of L-AmB., Expert Opinion: L-AmB is a broad-spectrum antifungal agent that has significantly reduced toxicities compared to its predecessor, DAmB.

Objective: To evaluate the impact of a multi-approach strategy to improve the appropriate usage of acid suppressive medication (ASM) in medical inpatients and compare it with the baseline data from 2007., Setting: Five general medicine wards in a 600-bed teaching hospital in Doha, Qatar., Method: A prospective evaluation of the usage of ASM 1 year after a multi-approach strategy. This consisted of four main interventions: audit and feedback method (including awareness lectures to all medical and pharmacy staff), implementation of a usage guideline for medical inpatients, circulating a logarithmic chart on the proper usage of ASM for medical inpatients from admission through to discharge and participation of clinical pharmacists in the multidisciplinary rounds. All medical patients admitted from May through June 2009 were evaluated. Data about the usage of ASM were collected upon and during admission, at discharge and at the next follow-up visit. Justified indications for its usage were based on the approved product information and on evidence-based literature recommendations. Data were compared with the findings of the baseline clinical audit done 2 years earlier., Main Outcome Measure: The usage of ASM in justified and non-justified indications upon and during admission, at discharge and at the next follow up visit., Results: A total of 414 patients were admitted during the study period, 208 patients (50%) received ASM compared to 53% in 2007 (206 patients out of 389). Seventy-four patients (36%) were using ASM upon admission compared to 48 patients (23%) in the 2007 clinical audit. Inappropriate ASM use decreased with 51% during admission (66 to 32%, P < 0.0001), 62% at discharge (34 to 13%, P < 0.0001) and 67% at the next follow up visit (15 to 5%, P = 0.0008)., Conclusion: Despite the higher number of patients receiving ASM upon admission, the multi-approach strategy used in our institution resulted in a significant improvement in the appropriate usage of ASM in medical inpatients.