Recycling transplanted organs: An exceptional case and literature review.

BACKGROUND: Recycling transplant kidneys, in other words using an allograft which has previously been transplanted in one recipient for transplant in a second recipient, can be a source of opportunity for expanding the pool of available grafts in the United States and beyond. SUMMARY: We describe a case of renal transplantation from a donor who had undergone a kidney transplant 3 years prior and had good graft function at the time of procurement. The recipient underwent transplantation uneventfully and to date has demonstrated excellent graft function. We also include a literature review of reported cases of recycled/retransplanted kidneys. KEY MESSAGES: -Recycling transplanted kidneys is a largely untapped resource which could help decrease the transplant waitlist. -Utilizing such kidneys does need special considerations in terms of procurement technique, backtable, crossmatch, recipient selection and follow-up.

SWI/SNF chromatin remodeling subunit Smarca4/BRG1 is essential for female fertility†.

Mammalian folliculogenesis is a complex process that involves the regulation of chromatin structure for gene expression and oocyte meiotic resumption. The SWI/SNF complex is a chromatin remodeler using either Brahma-regulated gene 1 (BRG1) or BRM (encoded by Smarca4 and Smarca2, respectively) as its catalytic subunit. SMARCA4 loss of expression is associated with a rare type of ovarian cancer; however, its function during folliculogenesis remains poorly understood. In this study, we describe the phenotype of BRG1 mutant mice to better understand its role in female fertility. Although no tumor emerged from BRG1 mutant mice, conditional depletion of Brg1 in the granulosa cells (GCs) of Brg1fl/fl;Amhr2-Cre mice caused sterility, whereas conditional depletion of Brg1 in the oocytes of Brg1fl/fl;Gdf9-Cre mice resulted in subfertility. Recovery of cumulus-oocyte complexes after natural mating or superovulation showed no significant difference in the Brg1fl/fl;Amhr2-Cre mutant mice and significantly fewer oocytes in the Brg1fl/fl;Gdf9-Cre mutant mice compared with controls, which may account for the subfertility. Interestingly, the evaluation of oocyte developmental competence by in vitro culture of retrieved two-cell embryos indicated that oocytes originating from the Brg1fl/fl;Amhr2-Cre mice did not reach the blastocyst stage and had higher rates of mitotic defects, including micronuclei. Together, these results indicate that BRG1 plays an important role in female fertility by regulating granulosa and oocyte functions during follicle growth and is needed for the acquisition of oocyte developmental competence.

Isolated arterial mucoid intimal thickening lesion in early post-transplant kidney allograft biopsies.

INTRODUCTION: Thrombotic microangiopathy (TMA) on kidney biopsy shows a variable combination of features: arterial mucoid intimal thickening, acellular closure of glomerular capillary loops, fragmented red blood cells, fibrin thrombi, and arterial fibrinoid necrosis. However, some early post-transplant kidney biopsies show only arterial mucoid intimal thickening. We aimed to elucidate the importance of this finding. METHODS: We identified 19 biopsies showing isolated arterial mucoid intimal thickening and compared them with 22 bona fide TMA biopsies identified based on the pathological findings (excluding rejection) (2011-2020). Additionally, delayed graft function (DGF) (n = 237), and no DGF (control, n = 1314) groups were included for survival analysis. RESULTS: Seven of 19 cases with isolated arterial mucoid intimal thickening showed peripheral blood schistocytes but no other systemic features of TMA. Eight patients underwent adjustments in maintenance immunosuppression (mainly calcineurin inhibitors). None of the cases progressed to full-blown TMA on consecutive biopsies. The overall and death-censored graft survival rates in this group were comparable to the DGF group, but significantly better than the TMA group (P = .005 and .04, respectively). CONCLUSIONS: Isolated arterial mucoid intimal thickening in early post-transplant biopsies may be an early/mild form of TMA, probably requiring adjustment in immunosuppressive regimen. Careful exclusion of known causes of TMA, and donor-derived arterial injury are important.

Topiramate affords neuroprotection in diabetic neuropathy model via downregulating spinal GFAP/inflammatory burden and improving neurofilament production.

The current study aimed to test the neuroprotective action of topiramate in mouse peripheral diabetic neuropathy (DN) and explored some mechanisms underlying this action. Mice were assigned as vehicle group, DN group, DN + topiramate 10-mg/kg and DN + topiramate 30-mg/kg. Mice were tested for allodynia and hyperalgesia and then spinal cord and sciatic nerves specimens were examined microscopically and neurofilament heavy chain (NEFH) immunostaining was performed. Results indicated that DN mice had lower the hotplate latency time (0.46-fold of latency to licking) and lower von-Frey test pain threshold (0.6-fold of filament size) while treatment with topiramate increased these values significantly. Sciatic nerves from DN control mice showed axonal degeneration while spinal cords showed elevated GFAP (5.6-fold) and inflammatory cytokines (∼3- to 4-fold) but lower plasticity as indicated by GAP-43 (0.25-fold). Topiramate produced neuroprotection and suppressed spinal cord GFAP/inflammation but enhanced GAP-43. This study reinforces topiramate as neuroprotection and explained some mechanisms included in alleviating neuropathy.

Crizotinib induced antitumor activity and synergized with chemotherapy and hormonal drugs in breast cancer cells via downregulating MET and estrogen receptor levels.

MET is a receptor tyrosine kinase known to drive neoplastic transformation and aggressive tumor phenotypes. Crizotinib is an oral multi-targeted tyrosine kinase inhibitor of MET, ALK, RON, and ROS1 kinases. In this study, the anticancer effects of crizotinib on breast cancer cells were investigated in vitro along with the molecular mechanisms associated with these effects. Besides, the antiproliferative effects of crizotinib in combination with chemotherapy, hormonal drugs, and targeted agents were examined. Results showed that crizotinib produced dose-dependent antiproliferative effects in BT-474 and SK-BR-3 breast cancer cells with IC50 values of 1.7 µM and 5.2 µM, respectively. Crizotinib inhibited colony formation of BT-474 cells at low micromolar concentrations (1-5 µM). Immunofluorescence and Western blotting indicated that crizotinib reduced total levels of MET and estrogen receptor (ERα) in BT-474 cells. Also, crizotinib reduced the levels of phosphorylated (active) MET and HER2 in BT-474 cells. The combined treatment of crizotinib with doxorubicin and paclitaxel resulted in synergistic growth inhibition of BT-474 cells with combination index values of 0.46 and 0.35, respectively. Synergy was also observed with the combination of crizotinib with the hormonal drugs 4-hydroxytamoxifen and fulvestrant in BT-474 cells. Alternatively, the combination of crizotinib with lapatinib produced antagonistic antiproliferative effects in both BT-474 and SK-BR-3 cells. Collectively, these findings demonstrate the anticancer effects of crizotinib in breast cancer cells and reveal ERα as a potential therapeutic target of the drug apart from its classical kinase inhibitory activity. Crizotinib could be an appealing option in combination with chemotherapy or hormonal drugs for the management of breast cancer.

Mac-2 binding protein glycan isomer as noninvasive tool to assess liver fibrosis in children with chronic liver disease.

AIM: This study is aimed to measure the value of serum Mac-2 binding protein glycan isomer (M2BPGI) in children with chronic liver diseases in comparison with liver biopsy and serum biomarkers. METHODS: Comparative cross-sectional study included 100 children with chronic liver diseases and 50 healthy age/sex-matched control group. All subjects were evaluated via medical history, clinical, radiological and laboratory examinations. Liver biopsy was performed for studied patients and serum M2BPGI level was measured by Enzyme Linked Immune Sorbent Assay (ELISA) in all studied subjects. RESULTS: Serum M2BPGI level increased more significantly in chronic liver disease patients (6.04 ± 2.72 ng/ml) than in healthy controls (1.12 ± 0.83 ng/ml) (P < 0.001). M2BPGI level was significantly elevated with progressive fibrosis (P < 0.001), and differed significantly between high and low Child-Pugh score, pediatric end-stage liver disease score and model for end-stage liver disease score score. Serum M2BPGI was correlated with serum biomarkers and degree of fibrosis in patients. CONCLUSION: M2BPGI could be used as one of noninvasive tools for detecting and staging of hepatic fibrosis in Egyptian children with chronic liver disease.

Proinflammatory cytokine polarization in type 2 diabetes.

Subclinical inflammatory reaction is associated with non-insulin dependent diabetes. Therefore, the aim of the present study is to describe the effect of the three cytokines: interferon γ (IFN-γ), interleukin (IL)-4 and IL-5 on the development of type 2 diabetes (T2D). Forty-five volunteers (after their permission) were participated in this work; according to their clinical examination and laboratory investigations (fasting blood sugar, 2 hours postprandial, HbA1c and lipid profile), they were divided into thirteen control (non-diabetic) (five females and eight males) and thirty-two diabetic patients (twenty-one females and eleven males). Thereafter, their sera were evaluated for C-reactive protein (CRP), IFN-γ, IL-4 and IL-5. The results revealed an increasing trend of CRP and a significant increase of IFN-γ in diabetic patients with no sex difference. A positive correlation between IFN-γ and both IL-4 and IL-5 in control, and a positive correlation between IL-4 and IL-5 in diabetic patients had been visualized. These results denoted that there may be an association of the pro-inflammatory cytokines in the etiology of diabetes mellitus type 2.

Onset of Appearance and Potential Significance of Telocytes in the Developing Fetal Lung.

CD34, vimentin, and vascular endothelial growth factor immunohistochemical analysis and electron microscopic tools were employed to record the initial appearance of telocytes (TCs) and stage-by-stage variations in TC localizations in the developing rabbit lung. TCs could not be identified in the primitive embryonic lung until day 18 of gestation. In the pseudoglandular lung, CD34+ TCs had been recorded under the cartilage of the main bronchus, in the wall of large-sized pulmonary vessels and large epithelial tubes. In the canalicular phase, TCs could be demonstrated in the smooth muscle layer of the bronchioles including the terminal ones. The strength of CD34 immunoreactive signals had been amplified by age until the day of parturition. Ultrastructurally, TCs consisted of a tiny body and exceptionally long telopodes (Tps). The Tp consisted of alternating thin segments (podomers) and dilated ones (podoms). The Tp sometimes branched with a dichotomous pattern. TCs interconnected in a network either by homocellular junctions with neighboring TCs or by heterocellular junctions with smooth muscle cells and alveolar cells. Collectively, early detection of TCs in pulmonary vessels suggests a potential role for TCs in their angiogenesis. For the lung tissue, TCs seem to be involved in the regulation of lung histogenesis.

Immunohistochemical and Ultrastructural Features of the Seasonal Changes in the Epididymal Epithelium of Camel (Camelus dromedarius).

In order to evaluate the influence of reproductive activity on the functional role of the epididymal epithelium in the Egyptian dromedary camel, Connexin-43 (Cx-43), vascular endothelial growth factor (VEGF), and androgen receptor (AR) immunoreactivity in the epididymal epithelium and the fine structure of the principal, dark, basal, apical, and halo cells were investigated. The secretory activity of the principal cells was amplified in the breeding season, while its endocytotic function became more active in the nonbreeding season. This was evidenced by punctate strong immunoreactive signals for Cx-43, which appeared to be more intense in the apical region of these epithelial cells, and the extremely long slender stereocilia (microvilli) with multiple junctional complexes. The nonbreeding principal cells revealed granular immunoreactive signals for VEGF scattered in the apical and basal cytoplasm. Ultrastructurally, both extreme vacuolation and several multivesicular inclusion bodies were observed in their cytoplasm. Dark cell size greatly diminished in the nonbreeding season and their nuclear morphology greatly changed from oval to lobulated shape. The plasma membrane of the apical cells expressed several infoldings (microvilli) in the breeding season. However, it was almost smooth in the nonbreeding season except for a small microvillus that appeared as a bleb-like projection. In some regions, a strong dense immunoreactivity for VEGF could be recognized in the cytoplasm of the apical cells and some basal ones. Halo cells with numerous multivesicular inclusions occupying most of the cytoplasm and a lobulated eccentric nucleus were detected in the nonbreeding season. In conclusion, these findings indicate that the reproductive activity has a significant impact on the immunohistochemical and ultrastructural profiles of the epithelial cells lining the Egyptian dromedary camel epididymis.

Immunolocalization of Receptor and Chemoreceptor Modules in the Sheep Vomeronasal Organ.

The vomeronasal organ (VNO) is the peripheral receptor organ of the accessory olfactory system, which is responsible for both sexual and innate behaviors. The degree of neuronal differentiation and maturation of the vomeronasal receptor cells together with the verification of the presence of the solitary chemoreceptor cells (SCCs) in the VNO of Corriedale sheep were assessed using immunofluorescence. A protein gene product 9.5 (PGP 9.5), which is a neuronal marker recognized to be expressed in most neurons of vertebrate species, an olfactory marker protein (OMP) that is precise for mature olfactory receptor cells, and lastly phospholipase C-ß2 (PLC-ß2), a marker in the signal transduction pathway of SCCs, were all tested. The cell bodies and dendrites of almost all receptor cells in the sensory epithelium were strongly positive for PGP 9.5 and to a lesser extent for OMP. In the nonsensory wall, all cells were negative for both PGP 9.5 and OMP; however, some positive PGP 9.5 immunoreactive fibers were identified. For PLC-ß2, only 1 basally situated SCC could be identified in the sensory epithelium. A higher number was demonstrated in the nonsensory wall. Corriedale sheep possess matured, fully differentiated vomeronasal receptor cells in their sensory wall, suggesting an appropriate pheromone perception. Additionally, the VNO in sheep may participate in the usual transduction mechanisms, though it is seemingly not a chemoreceptor organ.

Cognitive Impairment and Tramadol Dependence.

BACKGROUND AND OBJECTIVE: Cognitive impairment is one of the consequences of substance abuse. Tramadol abuse is a public health problem in Egypt. The objective of this study was to estimate the prevalence and correlates of cognitive impairment among tramadol-abuse patients and control subjects. METHODS: This study included 100 patients with tramadol abuse and 100 control subjects (matched for age, sex, and education) who were recruited from Zagazig University Hospital, Egypt. Patients were divided into 2 groups: patients who used tramadol only (tramadol-alone group) and patients who used tramadol and other substances (polysubstance group). The participants were interviewed using Montreal Cognitive Assessment test and had urine screening for drugs. RESULTS: Twenty-four percent of the cases used tramadol alone, whereas the remaining used tramadol and other substances, mainly cannabis (66%) and benzodiazepines (27%). Tramadol-abuse patients were about 3 times more likely to have cognitive impairment than control subjects (81% vs 28%). Tramadol-alone patients were more than 2 times more likely to have cognitive impairment than control subjects (67% vs 28%). Cognitive impairment was significantly associated with polysubstance abuse. There was no association between cognitive impairment and sociodemographic or clinical factors. CONCLUSIONS: Cognitive impairment occurs commonly among tramadol-abuse patients. Memory impairment is the most common cognitive domain to be affected. There is a significant association between cognitive impairment and polysubstance abuse.

Impact of the Order of Movement on the Median Nerve Root Function: A Neurophysiological Study with Implications for Neurodynamic Exercise Sequencing.

Background: Neurodynamic exercise is a common clinical practice used to restore neural dynamic balance. The order in which movements are performed during these exercises is believed to play a crucial role in their effectiveness. This study aimed to investigate the impact of different sequences of neurodynamic exercise on nerve root function, with a specific focus on the median nerve. Methods: Participants were assigned randomly to three experimental groups, each undergoing a different test sequence: standard, proximal-to-distal, and distal-to-proximal. Dermatomal somatosensory evoked potentials (DSSEPs) were recorded at key levels (C6, C7, C8, and T1). Results: The findings revealed a significant influence of the movement sequence on DSSEP amplitudes. The execution of neurodynamic exercise in the proximal-to-distal sequence was associated with a notable reduction in amplitudes (p < 0.05). Conversely, the distal-to-proximal sequence resulted in increased amplitudes compared to the standard sequence (p < 0.05). Conclusions: This study underscores the importance of carefully considering the order of movements during neurodynamic exercising, particularly when evaluating nerve roots that lack the protective perineurium. The choice of sequence appears to have a substantial impact on nerve function, with implications for optimizing clinical neurodynamic exercise techniques.

Pathogenesis and prognosis of neutropenia in infants and children admitted in a university children hospital in Egypt.

This study aimed to assess the prevalence, severity, and etiology of neutropenia in infants and children admitted to a children's hospital in Egypt. A total of 200 patients with neutropenia were recruited from April 1, 2010 to September 30, 2010. Patients with a known hematological or immunological disease were excluded. Patients were followed till recovery or an underlying cause was uncovered. Viral serological analysis was done for patients with moderate/severe neutropenia, including cytomegalovirus (CMV); Epstein-Barr virus (EBV); hepatitis A, B, and C viruses; and HIV. Antineutrophil cytoplasmic antibody (ANCA) tested by enzyme immunoassay and bone marrow aspirate were done for prolonged neutropenia. The results revealed that neutropenia was mild in 90 (45%), moderate in 56 (28%), and severe in 54 (27%). Clinical diagnosis at admission was bronchopneumonia (38%), pyrexia of undetermined etiology (17%), bronchiolitis (13%), urinary tract infection (9%), acute gastroenteritis (8%), hepatitis (6.5%), and septicemia (5%). Patients with mild neutropenia recovered within 1 week. Among 110 patients with moderate/severe neutropenia, 80 (73%) recovered in <3 weeks. Predictors of prolonged neutropenia were age younger than 18 months (P < .01), absolute neutrophils count (ANC) < 500/mm(3) (P < .05), hemoglobin < 10 gm/dL (P < .05), and positive CMV serology (P < .01). CMV and EBV serology were positive in 34.5% and 7.3% of patients, respectively. ANCA was positive in 42.8% of patients with prolonged severe neutropenia. In conclusion, neutropenia is a frequent finding in Egyptian infants and children, usually mild and transient, and mainly associated with infection. CMV and EBV are associated with prolonged neutropenia. Immune neutropenia is a common cause of moderate/severe neutropenia in the first two years of life.

Correlation of Red Blood Cell Casts With Renal Dysfunction in Patients With Infection-related Glomerulonephritis.

CONTEXT.­: Infection-related glomerulonephritis (IRGN) usually manifests as a proliferative immune-complex glomerulonephritis. The degree of renal dysfunction at presentation can vary. Association with histologic features on kidney biopsy remains unknown. OBJECTIVE.­: To study the correlation between renal function in IRGN at the time of biopsy and the severity of histologic features. DESIGN.­: Culture-proven IRGN cases at our facility were included and divided based on estimated glomerular filtration rate (eGFR) 15 ml/min/1.73 m2. Patients' demographic and pathologic findings were obtained from electronic medical records and kidney biopsy reports. RESULTS.­: In total, 104 cases were diagnosed with IRGN on biopsy (mean age, 55.6 ± 15.6 years; male, n = 79 [76%]; median eGFR, 14.5 mL/min/1.73 m2), and 51 of 104 showed eGFR <15 mL/min/1.73 m2. Among all the histologic features assessed, only percent tubules with red blood cell (RBC) casts showed statistical difference, being significantly higher in the lower eGFR group (P = .004). Multivariable logistic regression analysis also showed that %tubules with RBC casts were associated with lower eGFR (odds ratio, 1.12; 95% CI, 1.01-1.24; P = .01). Patients with 5% or more RBC casts (n = 31) showed a lower eGFR (P = .02) and a higher %cellular crescent (P < .001) compared with those with less than 5% RBC casts. Patients with concomitant anticoagulant therapy (n = 11) showed higher percentages of RBC casts than those without anticoagulants (P = .02). CONCLUSIONS.­: Particular attention to the extent of RBC casts on kidney biopsy is recommended in patients with IRGN because these portend worse renal dysfunction, more so in patients requiring anticoagulation (including for hemodialysis) because they are especially vulnerable to developing anticoagulant-related nephropathy.

Plasma Wnt7b protein in rheumatoid arthritis: Detection of interstitial lung disease.

OBJECTIVE: To determine the plasma level of Wingless-related integration site 7b (Wnt7b) protein in rheumatoid arthritis (RA) patients (with and without interstitial lung disease (ILD)) and in idiopathic pulmonary fibrosis (IPF) patients and its relationship with RA disease activity and/or severity of pulmonary fibrosis. To assess the validity of plasma Wnt7b for the detection of ILD among RA patients. METHOD: This case-control study included 128 subjects (32 RA-ILD, 32 RA, 32 IPF, and 32 healthy controls). RA and RA-ILD Patients were evaluated for disease activity by DAS28 and disease activity grades were recorded according to DAS28 grades. Laboratory parameters as Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid Factor (RF), Anti-citrullinated peptide (Anti-CCP) were recorded. Plasma Wnt7b levels were measured by ELISA. Diagnosis of pulmonary fibrosis (for RA-ILD and IPF patients) was done by high resolution computed tomography (HRCT) and its severity was assessed mainly by pulmonary function test using forced vital capacity (FVC) grading. RESULTS: Comparison of Wnt7b plasma levels showed a significant difference between the studied groups with the P-value < 0.018 (RA-ILD had the highest levels). Post hoc analysis revealed a significant difference in Wnt7b plasma levels between RA-ILD and IPF groups (P = 0.008). Also, RA-ILD and control groups had a significant difference (P = 0.039). However, there was a non-significant relationship between Wnt7b plasma levels and RA disease activity as well as the severity of pulmonary fibrosis. ROC curve analysis for the plasma Wnt7b levels revealed that a level  ≥285.1 pg/ml had a sensitivity of 87.5% and a specificity of 43.8% for the detection of ILD in RA patients with positive likelihood ratio of 1.56 and negative likelihood ratio of 0.29. CONCLUSION: RA-ILD patients had significantly higher plasma Wnt7b levels than the controls and IPF patients. These data suggest that the Wnt7b secretion is augmented by the concomitant presence of RA with pulmonary fibrosis. In addition, plasma Wnt7b may be used as a highly sensitive test for the detection of immunologically induced fibrotic changes in lung tissue among RA patients.

Therapeutic potential of bone marrow mesenchymal stem cells in cyclophosphamide-induced infertility.

Cancer is a deadly disease characterized by abnormal cell proliferation. Chemotherapy is one technique of cancer treatment. Cyclophosphamide (CYP) is the most powerful chemotherapy medication, yet it has serious adverse effects. It is an antimitotic medicine that regulates cell proliferation and primarily targets quickly dividing cells, and it has been related to varying levels of infertility in humans. In the current study, we assessed the biochemical, histological, and microscopic evaluations of testicular damage following cyclophosphamide administration. Further, we have explored the potential protective impact of mesenchymal stem cell (MSCs) transplantation. The biochemical results revealed that administration of cyclophosphamide increased serum concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), while it decreased serum concentrations of free testosterone hormone (TH), testicular follicle-stimulating hormone, luteinizing hormone, and free testosterone hormone concentrations, testicular total antioxidant capacity (TAC), and testicular activity of superoxide dismutase (SOD) enzyme. The histology and sperm examinations revealed that cyclophosphamide induced destruction to the architectures of several tissues in the testes, which drastically reduced the Johnsen score as well as the spermatogenesis process. Surprisingly, transplantation of mesenchymal stem cell after cyclophosphamide administration altered the deterioration effect of cyclophosphamide injury on the testicular tissues, as demonstrated by biochemical and histological analysis. Our results indicated alleviation of serum and testicular sex hormones, as well as testicular oxidative stress markers (total antioxidant capacity and superoxide dismutase activity), and nearly restored the normal appearance of the testicular tissues, Johnsen score, and spermatogenesis process. In conclusion, our work emphasizes the protective pharmacological use of mesenchymal stem cell to mitigate the effects of cyclophosphamide on testicular tissues that impair the spermatogenesis process following chemotherapy. These findings indicate that transferring mesenchymal stem cell to chemotherapy patients could significantly improve spermatogenesis.

BRCA1 and BRCA2 deficient tumour models generate distinct ovarian tumour microenvironments and differential responses to therapy.

Clinical trials are currently exploring combinations of PARP inhibitors and immunotherapies for the treatment of ovarian cancer, but their effects on the ovarian tumour microenvironment (TME) remain unclear. Here, we investigate how olaparib, PD-L1 monoclonal antibodies, and their combination can influence TME composition and survival of tumour-bearing mice. We further explored how BRCA deficiencies can influence the response to therapy. Olaparib and combination therapies similarly improved the median survival of Brca1- and Brca2-deficient tumour-bearing mice. Anti-PD-L1 monotherapy improved the survival of mice with Brca1-null tumours, but not Brca2-null tumours. A detailed analysis of the TME revealed that olaparib monotherapy resulted in a large number of immunosuppressive and immunomodulatory effects in the more inflamed Brca1-deficient TME but not Brca2-deficient tumours. Anti-PD-L1 treatment was mostly immunosuppressive, resulting in a systemic reduction of cytokines and a compensatory increase in PD-L1 expression. The results of the combination therapy generally resembled the effects of one or both of the monotherapies, along with unique changes observed in certain immune populations. In-silico analysis of RNA-seq data also revealed numerous differences between Brca-deficient tumour models, such as the expression of genes involved in inflammation, angiogenesis and PD-L1 expression. In summary, these findings shed light on the influence of novel therapeutics and BRCA mutations on the ovarian TME.

Concomitant Polyoma BK Virus and West Nile Virus in Renal Allografts.

Surveillance of the renal allograft recipient is essential when monitoring renal function to detect the early onset of rejection and alter therapeutic treatments to treat acute rejection or other causes and improve long-term graft function. If renal function begins to deteriorate, a renal biopsy is often indicated to assess the Banff grade of potential rejection or other causes, especially in the setting of polyoma BK viral load elevation. Although BK infection in the allograft is asymptomatic, reactivation of the virus is known to be associated with the acceleration of pathologic change and a poor outcome in the allograft. BK reactivation in a transplant kidney is not uncommon, and determining inflammation related to the virus versus acute rejection is paramount for appropriate immunosuppressive therapy management. We identified a concomitant polyoma BK virus and West Nile Virus (WNV) infection in two renal transplant patients which, to our knowledge, has not previously been reported. However, other concomitant infections have been reported in renal allografts including BK virus and cytomegalovirus (CMV), CMV and hepatitis C (HCV), and HCV and human immunodeficiency virus (HIV). As WNV has become endemic in many regions of the United States, and since the transmission of the virus via transplanted organs is associated with significant morbidity and mortality, it may be prudent to consider serologic screening for WNV in living donors prior to organ procurement. Regardless, the observation we made and report here should underscore the potential for concomitant viral infections that may be masked when a renal allograft has a significant inflammatory response to BK virus.

Drug policies' sensitivity towards women, pregnancy, and motherhood: a content analysis of national policy and programs from nine countries and their adherence to international guidelines.

BACKGROUND AND OBJECTIVES: Substance use in women is associated with unique psycho-social and physical vulnerabilities and poses complex challenges during pregnancy and motherhood. Gender-sensitive drug policy which considers the needs of women and their children could address these concerns. The objectives of this study were: (1) to systematically explore national-level drug policies' sensitivity and responsiveness to women, pregnant women, and children; and (2) to examine the adherence of drug policies with international guidelines for gender sensitivity in drug policy. METHODS: The research team was diverse professional backgrounds and nine countries. A summative content analysis of national drug policy documents, action plans, and strategies was performed. Specific documents focusing on women, pregnancy, and children were analysed. Specific themes and how frequently they appeared in the documents were identified. This quantification was an attempt to explore usage indicating the relative focus of the policies. A thematic map was developed to understand how national-level drug policies conceive and address specific concerns related to women who use drugs. We adapted the UNODC checklist for gender mainstreaming to assess policies' adherence to international guidelines. RESULTS: Twenty published documents from nine countries were reviewed. The common themes that emerged for women, pregnancy, and children were needs assessment, prevention, treatment, training, supply reduction, and collaboration and coordination. Custody of children was a unique theme for pregnant women. Specific psycho-social concerns and social reintegration were special themes for women, whereas legislation, harm reduction, research, and resource allocation were children-specific additional themes. For women-specific content analysis, special issues/concerns in women with drug misuse, need assessment, and prevention were the three most frequent themes; for the children-specific policies, prevention, training, and treatment comprised the three most occurring themes. For pregnant women/pregnancy, prevention, treatment, and child custody were the highest occurring themes. According to ratings of the countries' policies, there is limited adherence to international guidelines which ensure activities are in sync with the specific needs of women, pregnant women and their children. CONCLUSION: Our analysis should help policymakers revise, update and adapt national policies to ensure they are gender-responsive and address the needs of women, pregnant women and their children.

Proteus syndrome with sciatic nerve fibrolipomatous hamartoma: an uncommon finding in a rare disease: report of two cases with literature review.

Proteus syndrome is an extremely rare condition, characterized by progressive asymmetric overgrowth of multiple body tissues. Here, we present two cases of Proteus syndrome demonstrating typical clinical and radiological features of Proteus syndrome, in addition to an uncommon fibrolipomatous hamartoma of the sciatic nerve. The first case is a 5-year-old girl who presented with seizures. The patient showed facial dysmorphic features, left head enlargement, kyphoscoliosis, asymmetric overgrowth of the right lower limb, right foot drop, and cribriform connective tissue nevi on the right palm and the right sole. Radiological examinations demonstrated left calvarial hyperostosis, dysplasia of the left cerebral hemisphere, dysregulation of the subcutaneous adipose fat of the body, kyphoscoliosis, and lipoma of the filum terminale. CT of both thighs showed asymmetric soft tissue overgrowth of the right thigh, associated with diffuse enlargement and fatty infiltration of the right sciatic nerve starting from the upper thigh, down to its bifurcation into the tibial and common peroneal nerves. The second case is an 18-year-old girl who presented with left conductive deafness. The patient showed facial dysmorphic features, right head enlargement, asymmetric overgrowth of the right upper limb, kyphoscoliosis, left foot drop, and cribriform connective tissue nevi on the nose and the left foot. Radiological examinations demonstrated right calvarial hyperostosis, left external auditory canal hyperostosis and stenosis, and kyphoscoliosis. CT and MRI of both thighs showed diffuse enlargement of the left sciatic nerve starting from the upper thigh down to the mid-thigh and showing interfascicular adipose tissue proliferation, giving the typical features of nerve lipomatosis.