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Forebrain GABAergic neurons, the main inhibitory type of neuron in the cortex and hippocampus, represent a highly heterogeneous cell population that has been implicated in the predisposition to epilepsy and the onset of seizure. Earlier attempts to restore inhibition and reduce seizure in animal models of epilepsy have been carried out using embryonic basal forebrain tissue as source of immature GABAergic progenitors in cell-based therapies, with promising results. For therapeutic strategies this approach appears unrealistic, while the use of pluripotent stem cells to obtain immature GABAergic neurons opens new and promising avenues. Research on neural stem cells and pluripotent stem cells has greatly advanced and protocols have been established to efficiently direct progenitor cells to differentiate towards the GABAergic lineage. However, being highly heterogeneous, these neurons are difficult to be fully represented in vitro. Better knowledge on the expressed gene profiles, at single cell level, and the differentiation trajectory of these neurons will consent a more precise monitoring of the differentiation steps. Here we review the current literature about how to obtain and characterize genuine inhibitory neurons, how these can be grafted in animal models (and one day possibly in human) and which diseases could potentially be targeted and the efficiency of therapeutic outcome. The main obstacles that need to be overcome are: a) choice of an appropriate animal model, b) availability of human cells prone to GABA differentiation, c) the full representation of all IN subtypes, their proportions and their physiological activities, d) how to monitor them on the long-term after transplant.

Natural killer (NK) cells, the third population of lymphoid cells, comprise 5%-25% of peripheral blood (PB) lymphocytes and represent the first line of defense against infections and tumors [1-7]. They can be derived from: bone marrow, PB, cryopreserved umbilical cord blood (UCB), human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), and various cell lines such as NK-92 and KHYG-1 [1]. NK cells; which have been divided into cytotoxic, tolerant, and regulatory subsets; are classified into: (1) naïve CD56 bright CD 16 dim CD 3 dim cells, (2) mature CD56 dim CD16 bright CD3 dim cells, and (3) lymphoid tissue-resident CD69+/CXCR6+ NK cells [1,2,8-11]. Although NK cells have been traditionally considered as part of the innate immune system, they have recently been shown to exhibit many of the features associated with adaptive immunity [8,12]. The functions of NK cells which are influenced by several cytokines include: elimination of infected cells, destruction of cancer cells, reducing the incidence of graft versus host disease (GVHD) following hematopoietic stem cell transplantation (HSCT), and regulation of pregnancy outcome [10,11,13]. 

Mesenchymal stem cells (MSCs) conditioned medium (CM) has a promising prospect towards skin regeneration. Therefore, human dental pulp and adipose stem cells (DPSCs and ADSCs) were isolated, propagated and evaluated for their stemness and genetic stability over time in culture before making CM. We aimed to characterize the applicability of lyophilized ADSCs and DPSCs derived CM (AD-CM and DP-CM) at 5 mg, 10 mg and 20 mg for wound healing process. The ability of wound closure was assessed by direct human dermal fibroblast cell scratch assay, treated with variable concentrations of AD-CM and DP-CM in vitro. Additionally, we also assessed the expression of different cytokines and growth factors secreted from ADSCs and DPSCs in the CM relevant to the wound healing by cytokine array analysis. Our data demonstrates a significant effect of both the AD-CM and DP-CM in wound healing within 24 hrs compared to that in control.

Natural killer cells represent the first line of defense against infections and tumors and can be derived from various sources including: bone marrow, peripheral blood, specific types of human stem cells, and certain cell lines. The functions of natural killer cells are influenced by: several cytokines, activating and inhibitory receptors, as well as other immune cells such as dendritic cells and mesenchymal stem cells. Natural killer cells are attractive candidates for adoptive cellular therapy in patients with hematologic malignancies and solid tumors in addition to recipients of various forms of hematopoietic stem cell transplantation as they enhance antitumor effects without causing graft versus host disease. Several clinical trials have shown safety and efficacy of natural killer cell products obtained from autologous as well as allogeneic sources and used in conjunction with cytotoxic chemotherapy, monoclonal antibodies and novel agents. The following review, which includes extensive literature review on several aspects of natural killer cells, will give particular attention to: the rising role of natural killer cell therapies in patients with malignant hematological disorders, solid tumors and in recipients of stem cell therapies; preparation and manufacture of natural killer cell products; challenges facing the utilization of this form of cellular therapy including evolution of resistance; and maneuvers that can be employed to enhance the efficacy of natural killer cell therapies as well as suggested solutions to resolve the remaining challenges.

The pandemic of COVID-19 has adversely affected the world in many aspects. The health and economic sectors suffer most of the repercussions of this disease. The search for a cure for this rapidly spreading virus which is causing massive life losses worldwide requires clear understanding of the immunopathogenesis of this virus so as to develop pinpointed targeted therapies rather than relying mainly on supportive care measures and drug repurposing to fight this life-threatening virus infection. Neutrophils, neutrophil extracellular traps (NETs), and NETosis are not well studied not only in COVID-19, but also in coroviruses in general. The review will shed lights on the functions of neutrophils, NETs, and NETosis in various infectious complications as well as in sepsis and acute lung conditions in an attempt to understand their actual roles and in order to help in designing targeted therapies in the near future.

Infectious diseases are a leading cause of death worldwide [1,2]. The Mid-20th century witnessed most of the antimicrobial discoveries but recently there is dramatic shortage of new classes of antimicrobial agents due to failure to build a sustainable antimicrobial discovery platform [1-4]. For example, antibiotics comprise ˂ 1.5% of the compounds under investigation at the major pharmaceutical and biotechnology companies [1,5]. 

The oocyte is the female gamete that contributes not only half of the genetic material but also all of the cytoplasm to the zygote, supplying the transcripts, proteins, mitochondria and other components necessary for early embryonic development. The intrinsic oocyte quality is one of the main factors affecting the embryo yield, the implantation rate and the rate of healthy offspring. It is obvious that a fertilized oocyte must reach the blastocyst stage within 6–9 days in the proper culture conditions to have a significant chance of inducing a pregnancy and producing an offspring. The ability to sustain the first week of embryonic development is clearly influenced by the follicular status from which the oocyte is obtained indicating that this developmental potential is inherent within certain oocytes. Since most early embryos that do not reach the blastocyst stage are blocked at or close to the maternal to zygotic transition (MZT)-stage, which occurs at the eight-cell stage in cattle, one could speculate that incompetent oocytes fail to appropriately activate the embryonic genome. Oocyte selection based on glucose-6-phosphate dehydrogenase (G6PDH) activity has been successfully used to differentiate between competent and incompetent bovine oocytes. Recently, molecular regulation of genes regulating biological process of Brilliant Cresyl Blue staining (BCB) selected oocytes and embryos was investigated to explain their variation in quality and developmental potentiality. This short review will highlights some of these efforts that have been done in this interesting area of research.

We present a case of hypocomplementemic urticarial vasculitic syndrome (HUVS) who developed severe renal failure requiring ICU-level care. Our patient is a 66-year-old man who presented with abdominal pain, rash, confusion, oliguria, and shortness of breath. He was found to be in acute renal failure with leukocytosis and elevated lactate. Work-up for infectious, autoimmune, and hematologic malignant diseases was negative. The presence of chronic urticaria, abdominal pain, hypocomplementemia, and leukocytoclastic vasculitis on skin biopsy confirmed the diagnosis of HUVS. He required hemodialysis for renal failure as well as gastrostomy tube placement for nutritional support secondary to the development of mucosal ulcers, a rare finding in HUVS. He recovered with several months of high-dose steroids and hemodialysis. This case highlights the effectiveness of steroids for initial treatment of HUVS, and the relapsing and remitting nature of the disease. Providers should also be aware of the broad range of presenting symptoms such as mucosal lesions that may require nutritional support. Interestingly, unlike many previously reported cases of HUVS, our patient had not yet developed signs and symptoms of systemic lupus erythematosus, which often overlaps with HUVS.

Care of kidney transplant recipient remains complex and long-term graft survival is not seen in every transplant recipient. Due to reduced supply and increased demand of human organs, more transplants are carried out using marginal grafts on emergency lists. Transplant recipients have altered physiology due to known end-stage renal disease, recent surgery and the use of potent analgesic and immunosuppressive medications. Amongst the known surgical complications, urine leak remains the most common. It can result from poor graft preparation due to excessive peri ureteric or lower pole dissection or damage to lower polar artery resulting in ischemic necrosis. In addition, poor surgical technique, bladder outflow obstruction, iatrogenic injury to bladder or renal pelvis may contribute to urine leak. Ongoing urine leak may manifest itself as swelling, pain, high drain output, sepsis, ileus and eventual graft loss. Early identification, localisation and quantification of leak remain essential in management of these patients. In addition, sepsis should be identified and treated promptly as these patients are highly susceptible to infections. Early recognition of this complication can significantly reduce hospital stay, improve quality of life and reduce graft loss and mortality. In this article, we aim to develop an evidence-based management approach to a patient with urine leak using a clinical scenario.

Brucellosis is a zoonotic infection that is endemic in some Mediterranean countries, North Africa and the Middle East. Brucella is a rare cause of peritonitis in Peritoneal Dialysis (PD) population and in non-dialysis patients alike. We report here a challenging case of PD-related Brucella peritonitis in a 45-year-old Saudi male with late peritonitis that delivered some key learning throughout its course from presentation, diagnosis and treatment to catheter salvage attempts so as to circumvent PD failure. We provide an in-depth review of limited published literature on PD-related Brucella peritonitis (seven cases, and present case) and summarized the data on key clinical characteristics, management and PD technique outcome to benefit nephrologists when encountered with this rare presentation.

Prednisone-sensitive hypocomplementemia, renal insufficiency, and kidney biopsy demonstrating severe tubulointerstitial nephritis (TIN), storiform fibrosis, and tubulointerstitial immune deposits are typical of IgG4-related tubulointerstitial nephritis and hypocomplementemic interstitial nephritis. A diagnosis of hypocomplementemic interstitial nephritis requires clinical and pathologic exclusion of IgG4-related tubulointerstitial nephritis. We describe a patient with hypocomplementemic interstitial nephritis who did not develop diagnostic features of IgG4 related disease (RD) over 2-year follow-up. We conclude that hypocomplementemic interstitial nephritis could be on a biologic spectrum with IgG4-related disease, but not all cases will develop the abundance of IgG4-positive plasma cells, systemic manifestations, or elevated immunoglobulin levels characteristic of IgG4-RD.

Introduction: Chronic kidney disease is a costly and burdensome public health concern. Delayed recognition and treatment of CKD may predispose patients to unfavorable future outcomes and burden the healthcare services. The early detection of disease via screening programs is widely recommended. The present study is a hospital camp-based screening for detecting patients with chronic kidney disease in Varanasi from 2014-18. Methods: The study subjects constituted 436 apparently healthy adults (age ≥18 years) of Varanasi. Information on socio-demographic profile, personal characteristics and clinical investigations were recorded. Stepwise binary logistic regression analysis was applied to find the significant predictors of chronic kidney disease. Results: Median age of the study subjects was 40.5 years. There were 39.7% males and 60.3% females. Chronic kidney disease was found in 23.9% subjects. Underweight, diabetes mellitus, hypertension, smoking status and higher creatinine levels came out as significant predictors of chronic kidney disease. Conclusion: We screened apparently healthy individuals and found very high percentages of chronic kidney disease and its predictors. Henceforth, understanding the preventable and modifiable risk factors of chronic kidney disease becomes a prerequisite to intervene before risk populations reaches to irreversible stages of adverse future outcomes.

Background: Haemodialysis is the commonest method of Renal Replacement Therapy in Nigeria. Despite an advancement in the technicality and better understanding of haemodialysis, a number of complications are known to be associated with this procedure.. Objective: We aimed to highlight our experiences and share some of the uncommon complications encountered during haemodialysis and present the outcome of our patients. Subjects and methods: A retrospective review of 101 patients during the last two years was done. Data extracted include: sociodemographic characteristic, aetiology of kidney disease, type of vascular access, intradialytic complication and outcome of treatment. Results: The total number of dialysis session during the period was 823. Males constituted a higher proportion (64.4%) and were found to be older than female patients 49.8 vs 42.8 years (P=0.001). Majority (89.1%) had chronic kidney disease while chronic glomerulonephritis was the main cause of CKD as seen in about 45% of the patient. Due to the cost implication, only 2(1.98%) were able to undergo 3 sessions of dialysis per week for up to 1 month. Vascular access was femoral (66.3%), internal jugular vein (25.7%), while only 2% used Artero-venous-fistula and one patient had femoral vessel pseudoaneurysm from frequent cannulation. The commonest complication was hypotension which was present in 15.8%. Twenty-eight deaths were recorded, 44(43%) were either lost to follow up or absconded while 5% were transplanted at a referral centre. Conclusion: Challenges of renal replacement therapy is overwhelming in our country due to poor human and financial resources. Early diagnosis and adequate government support are advocated.

Anti-glomerular basement membrane (anti-GBM) disease is an uncommon autoimmune disease that classically presents as an aggressive necrotizing and crescentic glomerulonephritis (CG), with or without pulmonary hemorrhage, and typically does not relapse. The pathologic hallmark is linear staining of GBM for Immunoglobulin G (IgG) which binds to the alpha-3 chain of type IV collagen. Recent reports have noted the occurrence of anti-GBM disease with atypical clinical presentations. We describe a case of a 22-year-old female presenting an anti-GBM disease with typical histological features with a singular clinical presentation with lower limb edema, elevated serum creatinine and nephrotic range proteinuria. Renal biopsy showed signs of chronicity and direct immunofluorescence microscopy demonstrated diffuse, intense linear positivity for IgG. All serologic tests were negative, including anti-GBM antibodies. Hence, a diagnosis of atypical anti-GBM disease was made. The patient was treated initially with mycophenolate mofetil and corticosteroids. After 3 months she began to aggravate renal function so mycophenolate of mofetil was discontinued and a low dose cyclophosphamide was initiated.

Peritonitis is the main complication of peritoneal dialysis caused the withdrawal of treatment like peritoneal dialysis which was used as primary treatment modality few years back in Pakistan. With this motto to know the exact cause of peritonitis this retrospective study was done and 35 out of 42 pervious peritoneal dialysis patients who had peritonitis were analyzed using old data. A total of 57 bags of all these peritonitis patients were analyzed in department of microbiology during the year 2007-2011. Out of these bags positive culture was obtained from 42 bags (74%). Most of patients with positive culture were undergoing acute peritoneal dialysis 66.67% and rest were on chronic ambulatory peritoneal dialysis. Main concern was the yield of organisms causing culture positive peritonitis. It was found that bacterial peritonitis was positive in 80%, fungal peritonitis was 11% and mycobacterium tuberculosis peritonitis was 09%. Various culture techniques along with Gram Stain, Zeihl Nielsen Stain and Auramine stain were used for knowing the yield. Limitations: Old and only small available data of peritonitis patients and stop of further peritoneal dialysis.

The blood and drainage cultures are suggested for early diagnosis of bloodstream infection (BSI), which are time consuming and laborious. Nasal colonization of bacteria is one of the modalities, occasionally can predict BSI. We hypothesized that nasal culture, as an accessible fluid may be helpful to predict future BSI in hemodialysis patients. The present prospective study evaluated 63 patients undergoing maintenance hemodialysis at the Pars hospital dialysis center, Tehran, Iran, from November 2015 until February 2016. Nasal fluid of patients were collected from the 1–cm internal anterior part of both nostrils of patients by a sterile swab and cultured in Trypticase soy agar. All patients were followed for three months for BSI. The results of first nasal fluid sample revealed that 33.3% in first sampling and 27.0% in sampling had positive nasal fluid culture. The type of bacteria in all positive cases was Staphylococcus aureus. The rate of BSI infection in the patients with positive and negative first nasal fluid culture was 9.5% and 2.4% respectively with no significant difference. We found also no significant association between BSI positivity and nasal culture results so that positive BSI was revealed in 5.9% of patients with positive nasal fluid culture and 4.3% in those with negative nasal fluid culture with no meaningful difference. None of the baseline variables including age and gender, underlying risk factor, access, or duration of dialysis was associated with BSI positivity. In hemodialysis patients, BSI may not be predicted by nasal fluid culture positivity.

Background: In sickle cell anemia (SCA), compromise of the renal vasculature due to sickled red cells has been recognized. Objectives: To assess the renal function and blood pressure pattern in children with sickle cell anaemia (SCA) presenting in a tertiary institution. Method: A cross-sectional study of patients with sickle cell anaemia (SCA) over six months involving the use of questionnaires, general physical examination, blood pressure, investigations for haemoglobin genotype, urinalysis, serum creatinine, screening for hepatitis B and HIV. Results: 51 children with SCA were seen. The prevalence of impaired renal function as defined by reduced eGFR <90mL/min/1.73m2 in this study was 27.5%, previous hospital admission and blood transfusion were associated with reduction in eGFR but blood pressure did not have significant correlation with the eGFR. The overall mean age at diagnosis of SCA was 4.09 ± 3.33 (years). Conclusion: Impaired renal function is a major comorbid condition in children with SCA. In countries/locations where there is no newborn screening for sickle cell disease, diagnosis is delayed, thus detecting impaired renal function may be delayed, therefore the need for early detection and management is imperative.Introduction

Climate change and the increasing global population pose a severe threat to the availability of freshwater in the world. Over consumption of water and deteriorating water quality are problems that should be addressed in order to ensure water availability for the coming decades. In this context, the increasing presence of micropollutants in water has shown to cause detrimental impact on water quality, given the negative disturbances that they can cause on human health and on the environment. Thus, it is important to study and quantify the presence of micropollutants in water bodies and also in regenerated wastewater based irrigation systems. 

In recent years polyolefin nanocomposites are of great interest because of their high potential as materials with novel properties [1,2]. The properties of the nanocomposites are not only influenced by the kind of fillers but also by the microstructure of the polyolefin, the distribution of the fillers, and the preparation process. Nanocomposites prepared by extrusion moulding of mixed polyolefin and nanoparticles show often less stability by agglomeration of the nanoparticles. A better distribution is obtained if the polymerization catalyst is absorbed on the surface of the nanoparticles. After adding an olefin a growing film of the polyolefin is covering every nanoparticle (in situ polymerization). 

This literature review is concerning with liquid chromatography specifically high performance liquid chromatography (HPLC), Ultra high performance liquid chromatography (UHPLC), chromatography theory, chromatographic parameters, monolithic columns, principles of green chemistry and its application ingreen chromatography.