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.
ystemic sclerosis (SScl) is an autoimmune disorder of unknown aetiology, characterised by fibrosis and microvascular injury of the affected organs. The hallmark of the disease is thickening and tightness of the skin and the subcutaneous tissue. SScl can affect virtually any organ systems, most importantly the skin, blood vessels, lungs, kidneys, gastrointestinal tract, and the heart [1].
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].
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.
Purpose: Deficiency of Fetuin A, as a calcification inhibitor, is assumed to be involved in vascular calcification in patients on maintenance hemodialysis (MHD). This study examined the relationship between serum Fetuin-A and vascular and valvular calcification in a cohort of MHD patients.
Methods: The study was conducted on 122 MHD patients. Serum levels of calcium, phosphorus, parathormone, and Fetuin-A were tested. Intima-media thickness (IMT) ≥0.8 mm and the presence of stenosis>50% or plaques in carotid doppler sonography were considered as vascular calcification. Calcification of cardiac valves or mitral annular calcification in two-dimensional echocardiography, were considered as cardiac valvular calcification. The presence of any or both of the two conditions was defined as cardiovascular calcification (CVC).
Results: Fetuin-A was lower than normal in 37% of 122. Totally 106 patients (87%) had CVC, who were older (61±14 vs. 38±14 years, P<0.001), more affected by diabetes (54% vs. 13%, P=0.007), had a longer dialysis vintage (median 5 vs. 2 years, P=0.006), lower levels of creatinine (8.9±2.8 vs. 11.9±3.1 mg/dL, P<0.001) and higher levels of calcium (8.7±0.7 vs. 8.4±0.5 mg/dL, P=0.026). There was no significant difference in mean Fetuin-A level between the two groups (P=0.101). In logistic regression increased age (OR=1.1, CI 95%=1.1 - 1.2) and serum calcium (OR=2.8, CI 95%=1.1- 7.6), and diabetes mellitus (OR=7.4, CI 95%=1.1 - 47.4) were risk factors.
Conclusion: This study showed that 87% of our patients had vascular and/or valvular calcification. Increased age and calcium level and diabetes were the predictors of CVC, whereas Fetuin-A was not.
Background: Chronic Kidney Disease is no longer considered just a health burden today but a major health priority owing to its high treatment costs and poor outcome. World Kidney Day and International Women’s Day in 2018 coincided, thus offering an opportunity to reflect on the importance of women’s health, and specifically their kidney health. The current study aims to identify chronic kidney disease in women through a cross sectional screening in hospital based camp in Varanasi on World Kidney Day.
Methods: 138 females attending a health camp were screened for clinical parameters like serum creatinine, random blood sugar, and pregnancy complications. Demographic and anthropometric parameters were noted. Ordinal logistic regression analysis was used to find the predictors of chronic kidney disease stages.
Results: The median age of the participants was 36 years. The prevalence of chronic kidney disease was 6.4% with 1.4% of Stage 1, 2.1% of Stage 2, 1.4% of Stage 3 and 1.4% of Stage 4. Women with diabetes were nearly 4 times at a greater risk of developing higher stages of chronic kidney disease compared to women without it. With a unit increase in serum creatinine levels, women were nearly 13 times more likely to develop higher stages of chronic kidney disease.
Conclusion: Serum creatinine levels and diabetes were the significant predictors for the development of higher stages of chronic kidney disease. Early screening for kidney diseases in women could reduce the load of health care delivery system that is involved in renal replacement therapies.
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.
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.
The incorporation of tellurium into metal carbonyl using tellurium transfer/ extrusion reaction is presented in this work. The results bring one of the new ways to incorporate tellurium by transferring it from one molecule to another molecule, in comparison to the work so far where either insertion or extrusion reactions were shown. The reactions of PhC2TeC2Ph with the metal carbonyl cluster produced thermodynamically stable metal carbonyl tellurium clusters.
Lung cancer is the leading cause of cancer-related deaths worldwide, and almost accounts for 20% of these deaths, however, the cure rate is less than 10% [1]. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases of lung cancer [1], but fewer than 15% of individuals diagnosed with NSCLC can survive for more than 5 years, which poses a great threat to the patient’s life and health [2]. Recently, the incidence of lung cancer keeps dynamically growing, but more than 75% of patients at diagnosis has appeared local development or metastasis, missing the best period of surgery. Moreover, despite surgical treatment is the optimal choice for early-stage NSCLC patients, 30%-40% of patients with NSCLC develop tumor recurrence in a short time. Therefore, improving the prognosis of patients with lung cancer and predicting the long-term survival of patients is of particular importance [3]. At present, tumor and node metastasis (TNM) staging system, clinicopathological characteristics, visceral pleural invasion and marginal status are used to predict the disease progression and overall survival of NSCLC patients. There is no index which is stable, effective, reliable and less harmful to assess prognosis, predict recurrence risk and overall survival.
Background: Knowledge of pulmonary complications (PCs) in children after hematopoetic stem cell transplantation (allo-HSCT) is limited; most data are from adult studies.
Case: We describe a 8 year old girl with high risk acute myeloid leukemia who developed graft versus host disease (GVHD) on Day 20, Cytomegalovirus (CMV) pneumonia on Day 50 and Cryptogenic organizing pneumonia (COP) on Day 170 after allo-HSCT.
Discussion: Cryptogenic organizing pneumonia is a rare noninfectious PCs that can be idiopathic or have several risk factors as a secondary causes, such as viral respiratory infections, drugs, GVHD and allo-HSCT. Viral respiratory infections and alloimmune lung syndromes have been reported in a few patients who have undergone transplantation.
Conclusion: Transplant physicians should be kept in mind for the development of alloimmune lung syndrome in the form of COP following CMV pneumonia in patients after allo- HSCT
An enquiry into the lack of attention awarded to serotonin antagonism in the treatment of arterial thrombosis revealed that the mode of action of serotonin and its platelet receptor antagonists was an action upon thrombus growth, and not, as with other anti-platelet drugs upon the initiation of thrombosis. This lack of effect could explain why this approach has been considered not to be effective. However under conditions of arterial stenosis in which there is platelet activation by increased shear stress, and during the growth phase of arterial thrombi, serotonin 5HT2A antagonism has been demonstrated to have great potentcy in dispersing thrombotic obstruction to blood flow. This mode of action, the lack of participation of serotonin in haemostasis, and the absence of serotonin in wounds accounts for the proven lack of effect of effect of pure specific 5HT2A antagonists (i.e., not those with other actions) on operative bleeding and skin bleeding times. This lack of effect on haemostasis solves the dosing problem encountered with other anti-thrombotic drugs, with which drug concentration cannot be controlled with single fixed doses, leading to the association between increased anti-thrombotic efficacy and increased bleeding complications. Thus 5HT2A antagonism appears to be the preferred approach, from the point of view of safety and lack of bleeding risk; this consideration applies particularly to thrombosis therapy in the context of traumatic accidents, surgical operations and invasive procedures such as angioplasty.
Varicella zoster virus (VZV), a double-stranded DNA virus, is a highly contagious human neurotropic virus that belongs to the alpha group of herpes viruses [1-4]. Primary VZV infection (chickenpox) occurs in childhood then the virus becomes latent in the nerve ganglia [1,5-7]. Reactivation of the virus may occur decades later and cause herpes zoster (HZ) which is manifested by a typical painful skin eruption that has characteristic dermatomal distribution [1,5]. Reactivation of VZV is usually predisposed to: old age; comorbid medical conditions such as diabetes mellitus, chronic obstructive airway disease, and end-stage renal disease; and immunosuppression due to malignancy, autoimmune disorders, immunosuppressive therapies, trauma, cytotoxic chemotherapy, hematopoietic stem cell transplantation (HSCT), and solid organ transplantation (SOT) [1,5-7].
In 1901, ABO system of blood groups was determined by Karl Landsteiner. It is present in different organisms like rodents, primates that includes chimpanzees, bonobos etc. The blood groups type in this system depends on some genes that are specific ABO gene. Arachnophobia is the dread of creepy crawlies and different creature like spiders. Individuals suffering from arachnophobia generally feels uneasy in any place where they accept that they could harbour arachnids or their existence for example, webs. 100 samples of blood from volunteers were used for Blood group test. The Blood groups were tested and results were recorded after the test all the used kits were discarded. The results shows that there is no clear cut difference between the arachnophobic males and non-arachnophobic male’s percentages, so no relation found in males. Similarly, in females both phobic and non-phobic ladies have no differences in their result values so, no relation was found. Whereas, in case of arachnophobic males and females comparison no relation was found. So, there is no relationship between ABO blood group system and arachnophobia and there may be a relation between non-phobia and AB+, B+ blood group in males whereas, in females only B+ blood group have relation with non-phobia.
Essential Thrombocythemia (ET) is currently classified as a Philadelphia negative myeloproliferative neoplasm (MPN) together with polycythemia vera (PV) and primary myelofibrosis (PMF); the latter can be further divided in pre-fibrotic primary myelofibrosis (pre-PMF) and overt myelofibrosis, as listed in the revised 2016 World Health Organization classification of myeloid malignancies (WHO 2016). Overall, respect to the others MPNs, ET is characterized by favorable prognosis, lower life expectancy if compared to the control population, increased risk of thrombohemorrhagic complications along with possible evolution in myelofibrosis and leukemic transformation. In this review the authors will review current knowledge on biology, clinical aspects, prognosis and stratification of thrombotic risk, therapeutic options and outcome in ET patients.
Introduction: Erdheim-Chester disease (ECD) is a rare and difficult-to-treat non-Langerhans cell histiocytosis characterized by the excessive production and accumulation of histiocytes. This study reports a case of ECD, emphasizing both its diagnosis, assessment and treatment of the pain associated with the disease.
Case Report: Six years ago, a 39-year-old male patient presented with generalized pain of moderate intensity in the lower limbs that involved periods of greater intensity associated with ambulation. The diagnosis of histiocytosis associated with panhypopituitarism and adrenal insufficiency was proposed. For a specific diagnosis, a bone lesion biopsy was performed, revealing the presence of histiocytic proliferation that was CD1 negative, S100 protein positive, and CD68 negative. Therefore, the diagnosis of non-Langerhans histiocytosis known as ECD was confirmed. During the two years that followed, the patient presented with severe bone pain, particularly in the lower limbs and cranial vault, and the pain subsided to a certain extent with the use of tramadol and paracetamol. Because of the pain, the patient was unable to walk and became bedridden As the patient remained in severe pain, even after the administration of morphine, the opioid was changed from morphine (60mg/day) to oxycodone (30mg/day) for a convenient dosing schedule; furthermore, the oxycodone dosage was scheduled to increase to 40mg/day that same week. The patient experienced significant pain reduction, requiring rescue analgesia only once or twice a week.
Conclusion: To the best of our knowledge, this is the first case report on the characterization and treatment of pain specific to ECD, and we highlight that the patient had a good response to treatment.
Introduction: Fluid management is the cornerstone of treatment for acute pancreatitis (AP), but the proper rate and volume is still controversial. We aim to evaluate the role of aggressive hydration in AP patients.
Methods: We retrospectively reviewed and analyzed 279 hospitalized patients of AP. Severity was determined by the Revised Atlanta classification; validated clinical scores were also calculated based on clinical information upon presentation. We extracted amount of fluid received by at 6, 12, 24 and 48 hours after presentation. Aggressive hydration was defined as amount higher than 10 ml/kg bolus followed by infusion at 1.5 ml/kg/h. After direct comparison between aggressive versus non-aggressive hydration groups, propensity-score match was performed to control severity, APACHE II and BISAP score. Post-match comparison as well as a subgroup comparison were conducted.
Results: At 24 hours, 125 (44.8%) patients received aggressive hydration averaged at 5.1 L (2-18 L), while 154 (55.2%) patients received non-aggressive hydration averaged at 2.5 L. Post-match comparison showed that aggressive hydration group had longer hospital stay (MAP: 5.3 vs 4.5, p = 0.145, MSAP/SAP: 8.3 vs 4.8 d, p = 0.007), and higher rate of intensive care unit admission (mild: 12.9% vs 4.4%, p = 0.042, moderately severe or severe: 36.8% vs 3.1%, p = 0.001), while showed no difference in rate of mortality or re-admission by 1 year. In patients who presented without organ failure, aggressive hydration did not change the rate of development of organ failure (14.1% vs 12.5%, p = 0.731), but the aggressive hydration group had a trend towards longer hospital stay (5.5 vs 4.6 d, p = 0.083) and higher rate of MICU admission (12.1% vs 4.8%, p = 0.051)
The complicated process of cancer triggers many physiological systems like vascular endothelial functions and hemostasis, which signifies the increased risk of thrombosis, which triggers thromboembolic events resulting in increased mortality and morbidity [1-3]. Tumorigenesis contributes by activation of coagulation around the perivascular region [4].
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