Characterization and applications of glutaminase free L-asparaginase from indigenous Bacillus halotolerans ASN9.

L-asparaginase (L-ASNase) is a versatile anticancer and acrylamide reduction enzyme predominantly used in medical and food industries. However, the high specificity of L-asparaginase formulations for glutamine, low thermostability, and blood clearance are the major disadvantages. Present study describes production, characterization, and applications of glutaminase free extracellular L-asparaginase from indigenous Bacillus halotolerans ASN9 isolated from soil sample. L-asparaginase production was optimized in M9 medium (containing 0.2% sucrose and 1% L-asparagine) that yielded maximum L-ASNase with a specific activity of 256 U mg-1 at pH 6 and 37°C. L-asparaginase was purified through acetone precipitation and Sephadex G-100 column, yielding 48.9 and 24% recovery, respectively. Enzyme kinetics revealed a Vmax of 466 mM min-1 and Km of 0.097 mM. Purified L-ASNase showed no activity against glutamine. The purified glutaminase free L-ASNase has a molecular mass of 60 kDa and an optimum specific activity of 3083 U mg-1 at pH 7 and 37°C. The enzyme retains its activity and stability over a wide range of pH and temperature, in the presence of selected protein inhibitors (SDS, ß-mercaptoethanol), CoCl2, KCl, and NaCl. The enzyme also exhibited antioxidant activity against DPPH radical (IC50 value 70.7 µg mL-1) and anticancer activity against U87 human malignant glioma (IC50 55 µg mL-1) and Huh7 human hepatocellular carcinoma (IC50 37 µg mL-1) cell lines. Normal human embryonic kidney cells (HEK293) had greater than 80% cell viability with purified L-ASNase indicating its least cytotoxicity against normal cells. The present work identified potent glutaminase free L-ASNase from B. halotolerans ASN9 that performs well in a wide range of environmental conditions indicating its suitability for various commercial applications.

Inhibition of Na/K-ATPase signaling Attenuates Steatohepatitis and Atherosclerosis in Mice Fed a Western Diet.

We have previously reported that the α1 subunit of sodium-potassium adenosine triphosphatase (Na/K-ATPase), acts as a receptor and an amplifier for reactive oxygen species, in addition to its distinct pumping function. On this background, we speculated that the blockade of Na/K-ATPase-induced ROS amplification with a specific peptide, pNaKtide, might attenuate the development of steatohepatitis. To test this hypothesis, pNaKtide was administered to a murine model of NASH: the C57Bl6 mouse fed a "western" diet containing high amounts of fat and fructose. The administration of pNaKtide reduced obesity as well as hepatic steatosis, inflammation and fibrosis. Of interest, we also noted a marked improvement in mitochondrial fatty acid oxidation, insulin sensitivity, dyslipidemia and aortic streaking in this mouse model. To further elucidate the effects of pNaKtide on atherosclerosis, similar studies were performed in ApoE knockout mice also exposed to the western diet. In these mice, pNaKtide not only improved steatohepatitis, dyslipidemia, and insulin sensitivity but also ameliorated significant aortic atherosclerosis. Collectively, this study demonstrates that the Na/K-ATPase/ROS amplification loop contributes significantly to the development and progression of steatohepatitis and atherosclerosis. Furthermore, this study presents a potential treatment, the pNaKtide, for the metabolic syndrome phenotype.

Blockage of the Na-K-ATPase signaling-mediated oxidant amplification loop elongates red blood cell half-life and ameliorates uremic anemia induced by 5/6th PNx in C57BL/6 mice.

We have previously demonstrated that the Na-K-ATPase signaling-mediated oxidant amplification loop contributes to experimental uremic cardiomyopathy and anemia induced by 5/6th partial nephrectomy (PNx). This process can be ameliorated by systemic administration of the peptide pNaKtide, which was designed to block this oxidant amplification loop. The present study demonstrated that the PNx-induced anemia is characterized by marked decreases in red blood cell (RBC) survival as assessed by biotinylated RBC clearance and eryptosis as assessed by annexin V binding. No significant change in iron homeostasis was observed. Examination of plasma samples demonstrated that PNx induced significant increases in systemic oxidant stress as assessed by protein carbonylation, plasma erythropoietin concentration, and blood urea nitrogen. Systemic administration of pNaKtide, but not NaKtide (pNaKtide without the TAT leader sequence) and a scramble "pNaKtide" (sc-pNaKtide), led to the normalization of hematocrit, RBC survival, and plasma protein carbonylation. Administration of the three peptides had no significant effect on PNx-induced increases in plasma erythropoietin and blood urea nitrogen without notable changes in iron metabolism. These data indicate that blockage of the Na-K-ATPase signaling-mediated oxidant amplification loop ameliorates the anemia of experimental renal failure by increasing RBC survival.NEW & NOTEWORTHY The anemia of CKD is multifactorial, and the current treatment based primarily on stimulating bone marrow production of RBCs with erythropoietin or erythropoietin analogs is unsatisfactory. In a murine model of CKD that is complicated by anemia, blockade of Na-K-ATPase signaling with a specific peptide (pNaKtide) ameliorated the anemia primarily by increasing RBC survival. Should these results be confirmed in patients, this strategy may allow for novel and potentially additive strategies to treat the anemia of CKD.

A national survey to assess breast cancer awareness among the female university students of Pakistan.

The incidence of breast cancer is increasing in Pakistan as well as globally. Awareness of women about breast cancer plays a cornerstone role in its early detection, better management, and prevention. Keeping this in mind, a cross-sectional study was carried out to assess the awareness of female university students about breast cancer's risk factors, signs and symptoms, and breast cancer examination. The data was collected from female university students studying in Pakistan. A total of 774 participants completed the survey and recorded their responses on an online pre-tested self-administered questionnaire. Only 29.8% of the participants have identified breast cancer history in their first-degree relatives as a risk factor. Moreover, 14.1% of the participant considered that the use of oral contraceptives for more than 5 years can increase the risk of developing breast cancer. In addition, inward pulled nipple, wounds around the nipple, and abrupt changes in the breast size were considered as the sign and symptoms of breast cancer by 25.2%, 25.7%, and 31.7% of the participants, respectively. Moreover, only 20.9% of the participants identified the correct year for starting breast cancer examination and 44.4% of the respondents marked that mammography should be initiated after 40 years. Overall, the university female students of Pakistan were poorly aware of breast cancer's risk factors, signs and symptoms, and breast examination. This study has highlighted the need for initiation of aggressive strategies regarding breast cancer awareness in both the literate and illiterate female population of Pakistan.

Quercetin as a possible complementary agent for early-stage COVID-19: Concluding results of a randomized clinical trial.

Background: Quercetin, a natural polyphenol with demonstrated broad-spectrum antiviral, anti-inflammatory, and antioxidant properties, has been proposed as an adjuvant for early-stage coronavirus disease 2019 (COVID-19) infection. Objective: To explore the possible therapeutic effect of quercetin in outpatients with early-stage mild to moderate symptoms of COVID-19. Methods: This was an open-label randomized controlled clinical trial conducted at the department of medicine, King Edward Medical University, Lahore, PK. Patients were randomized to receive either standard of care (SC) plus an oral quercetin supplement (500 mg Quercetin Phytosome®, 1st week, TDS: 2nd week, BDS) (n = 50, quercetin group) or SC alone (n = 50, control group). Results: After one week of treatment, patients in the quercetin group showed a speedy recovery from COVID-19 as compared to the control group, i.e., 34 patients (vs. 12 in the control group) tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (p = 0.0004), and 26 patients (vs. 12 in the control group) had their COVID-19-associated acute symptoms resolved (p = 0.0051). Patients in the quercetin group also showed a significant fall in the serum lactate dehydrogenase (LDH) mean values i.e., from 406.56 ± 183.92 to 257.74 ± 110.73 U/L, p = 0.0001. Quercetin was well-tolerated by all the 50 patients, and no side effects were reported. Conclusion: Our results, suggest the possible therapeutic role of quercetin in early-stage COVID-19, including speedy clearance of SARS-CoV-2, early resolution of the acute symptoms and modulation of the host's hyperinflammatory response. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04861298.

Development & application of Conceptual Framework Model (CFM) for environmental risk assessment of contaminated lands.

Dumping sites are the most common types of contaminated lands as they pollute the environment. Environmental management of contaminated sites cannot be delivered effectively and efficiently without robust holistic & integrated risk assessment. Previous studies reveal the absence of a risk assessment model that holistically integrates all essential factors progressively and categorically. The study aimed to develop a holistic & integrated Conceptual Framework Model (CFM) for environmental risk assessment and to apply developed CFM on real-world existing Mahmood Booti Open Dumping Site (MBODS). CFM developed in this study had three main tiers i.e., baseline study, hazard identification & exposure assessment, and risk estimation. For the application of CFM, baseline data were collected and assessed. Water, leachate & soil samples were collected within 1000 m across the site and analyzed for physio-chemical parameters and heavy metals to estimate risk. Results of applied CFM depicted that Physico-chemical analysis of leachate, water, and soil revealed significant pollution levels. Heavy metal analysis exhibited that Ni, Pb, Mn, and Cr levels exceeded the allowable limits of the "World Health Organization" in leachate, water, and soil samples. It also revealed the existence of metals at the source (dumping site itself), pathway, and receptor of the dumping site. Ei r value for Ni, Pb and Cd from the study area manifested a serious probable risk to ecological integrities. Results for PERI from dumpsite demonstrated a serious ecological risk. It can be concluded that although Mahmood Booti dumping site has been at post-closure stage, it is a momentous source of hazardous toxic contaminants to the nearby inhabitants. The work presented in this paper may reproduce repeatedly to create site-specific risk assessment models of other contaminated lands in a cost-effective, consistent and cohesive manner. Application of CFM at Mahmood Booti Dumping site described detailed risk assessment which helps further in risk management.

Assessing the Frequency and Risk Factors Associated with Gastroesophageal Reflux Disease (GERD) in Southern Punjab, Pakistan.

PURPOSE: Gastroesophageal reflux disease (GERD) is a highly prevalent gastrointestinal disorder with modifiable risk factors and it is associated with considerable health and economic burden. The current study was conducted to assess the frequency and risk factors related to GERD in the previously unstudied population of Southern Punjab, Pakistan. METHODS: A cross-sectional study was conducted for assessing the frequency and risk factors of GERD by using a self-administered questionnaire. The gastroesophageal reflux disease questionnaire (GerdQ) was utilized to detect the presence of the disease. RESULTS: The study included 308 participants; among them, 55.2% were female and 44.8% were male. The participants diagnosed with GERD (GerdQ score ≥8) were 26.6%. The various risk factors like higher BMI, past disease and smoking history, frequent use of NSAIDs, soft drinks, pickles, and spicy foods were significantly associated with GERD. CONCLUSION: The present study showed that GERD is prevalent in Southern Punjab and is associated with various modifiable risk factors. The ascendance of GERD can be prevented by public health education and awareness campaigns.

Prospective Within-Patient Assessment of the Impact of an Unlabeled Octreotide Pre-dose on the Biodistribution and Tumor Uptake of 68Ga DOTATOC as Assessed by Dynamic Whole-body PET in Patients with Neuroendocrine Tumors: Implications for Diagnosis and Therapy.

PURPOSE: Gastroenteropancreatic neuroendocrine tumors (GEP NETs) are often associated with high expression of somatostatin receptors (SSTRs) which allows for PET/CT imaging with radiolabeled somatostatin analogs such as 68Ga-DOTATOC. The interplay between 68Ga-DOTATOC and the synthetic somatostatin analogs commonly used to manage patient symptoms may lead to competition between the labelled and unlabeled peptides for receptor binding sites and current product labelling recommends patients be taken off somatostatin analogs before imaging. In this study, we prospectively investigated in human patients the effect of a pre-dose of octreotide, a short-acting somatostatin analog, on the distribution of 68Ga-DOTATOC in GEP NETs and normal organs. PROCEDURE: Research participants with GEP NETs were studied on two occasions using dynamic whole-body 68Ga-DOTATOC PET/CT. The two imaging studies were performed within 21 days of each other, using an identical acquisition protocol except for the administration of 50 µg of short-acting octreotide (pre-dose) immediately before the second PET/CT. Paired t-tests were used to compare tracer uptake with and without octreotide, for tumor and various normal organs. RESULTS: Seven participants with a mean age of 53 ± 10 years were studied. Octreotide pre-dosing decreased radiotracer uptake in the normal liver and spleen by 25 % (p = 0.04) and 47 % (p = 0.05) respectively but did not significantly change uptake in tumor (p = 0.53), red marrow (p = 0.12), kidneys (p =0.57), or pituitary gland (p = 0.27). CONCLUSIONS: Our data indicate SSTR imaging can be improved with a pre-dose of unlabeled octreotide given just prior to injection of the radiotracer. These data suggest there may be no need to discontinue somatostatin analog therapy prior to PET/CT with 68Ga-DOTATOC, allowing for a simpler, less disruptive patient protocol. This approach warrants further study in a variety of settings.

Erythropoietin-Induced Hypertension: A Review of Pathogenesis, Treatment, and Role of Blood Viscosity.

Anemia is a common complication of certain chronic diseases and can be treated by stimulating hematopoietic cells to increase red blood cell count, and this action is achieved by recombinant human erythropoietin. In this review article, we have discussed about hypertension, which develops as a result of erythropoietin therapy. We have explored the pathogenesis of erythropoietin-induced hypertension and discussed some ways to prevent and treat this condition. Also, an attempt has been made to find out the role of blood viscosity in erythropoietin-induced hypertension. We conducted a comprehensive review of literature by collecting data from online databases like PubMed and Google Scholar. We mainly studied clinical trials that unraveled the mechanism of hypertension caused by erythropoietin. Hypertension is mainly caused due to enhanced vascular responsiveness to constrictors and impaired action of vasodilators. Role of blood viscosity in the pathogenesis of hypertension is doubtful due to the lack of consistency in the studies. Incidence of hypertension can be reduced by achieving slow correction of anemia and by switching to subcutaneous route of administration. Conventional anti-hypertensives have been found to be beneficial in the treatment. In some severe and persistent cases, temporary discontinuation of erythropoietin may be needed.

Isolated perforated jejunal diverticulitis: a case report.

Jejunal diverticulosis is a rare phenomenon often identified either incidentally on imaging or intra-operatively. Complications of jejunal diverticulosis are associated with high rates of mortality. For this reason, it remains important that this pathology is considered amongst differentials for an acute abdomen. A 78-year old gentleman presented with a short history of generalized lower abdominal pain. Computer tomography scan revealed a large inflammatory abscess relating to a perforated jejunal diverticulum. The patient was taken to theatre where he underwent small bowel resection with primary anastomosis. Early cross sectional imaging is vital to allow early diagnosis and prompt management of this pathology. Small bowel resection with primary anastomosis was associated with an excellent clinical outcome.

Atmospheric polycyclic aromatic hydrocarbons (PAHs) at urban settings in Pakistan: Spatial variations, sources and health risks.

For the first time, this study presents gaseous and particulate-bound (PM2.5) polycyclic aromatic hydrocarbons (PAHs) in ambient air samples collected from eight major cities of Pakistan. Diurnal air samples (gaseous and PM2.5) were collected in summer 2014 on polyurethane foam and quartz fiber filters using high volume-active air sampler. The US-EPA enlisted 16 priority PAHs in particulate and gaseous phase were measured on gas chromatograph equipped with mass spectrometer detector. The total PAHs concentrations ranged between 188 pg m-3 (in Gilgit), and 2340 pg m-3 (in Lahore). The decreasing order of PAHs concentrations in various cities was in the following order: Lahore > Rawalpindi > Multan > Faisalabad > Karachgi > Peshawar > Quetta > Gilgit. Phenanthrene showed the highest concentration, accounted 18% of total PAHs followed by fluoranthene (12% of total PAHs). This study showed that the gaseous fractions were predominant in the ambient air. Source apportionment analysis revealed that biomass combustion, vehicular emissions and diesel combustion in power generators were the potential PAHs emissions sources. The lifetime lungs cancer risk (LLCR) was in the range of 8.28 × 10-7 to 2.09 × 10-5 depicting mild cancer risk to the residents on exposure to atmospheric PAHs. Therefore, it is recommended to monitor atmospheric PAHs throughout the year and also adopt environmentally friendly fuels to reduce PAHs pollution and health risks in the country.

The potential role of Na-K-ATPase and its signaling in the development of anemia in chronic kidney disease.

Chronic kidney disease (CKD) is one of the most prominent diseases affecting our population today. According to the Factsheet published by Centers for Disease Control and Prevention (CDC), it effects approximately 15% of the total population in the United States in some way, shape, or form. Within the myriad of symptomatology associated with CKD, one of the most prevalent factors in terms of affecting quality of life is anemia. Anemia of CKD cannot be completely attributed to one mechanism or cause, but rather has a multifactorial origin in the pathophysiology of CKD. While briefly summarizing well-documented risk factors, this review, as a hypothesis, aims to explore the possible role of Na-K-ATPase and its signaling function [especially recent identified reactive oxygen species (ROS) amplification function] in the interwoven mechanisms of development of the anemia of CKD.

Legacy and emerging flame retardants (FRs) in the urban atmosphere of Pakistan: Diurnal variations, gas-particle partitioning and human health exposure.

Atmospheric concentration of legacy (LFRs) and emerging flame retardants (EFRs) including 8 polybrominated diphenyl ethers (PBDEs), 6 novel brominated flame retardants (NBFRs), 2 dechlorane plus isomers (DP), and 8 chlorinated organophosphate flame retardants (OPFRs) were consecutively measured in eight major cities across Pakistan. A total of 96 samples (48 PM2.5 & 48 PUFs) were analyzed and the concentrations of ∑8PBDEs (gaseous+particulate) ranged between 40.8 and 288 pg/m3 with an average value of 172 pg/m3. ∑6NBFRs ranged between 12.0 and 35.0 pg/m3 with an average value of 22.5 pg/m3 while ∑8OPFRs ranged between 12,900-40,800 pg/m3 with an average of 24,700 pg/m3. Among the studied sites, Faisalabad city exhibited the higher concentrations of FRs among all cities which might be a consequence of textile mills and garment manufacturing industries. While analyzing the diurnal patterns, OPFRs depicted higher concentrations during night-time. The estimated risks of all groups of FRs from inhalation of ambient air were negligible for all the cities, according to USEPA guidelines. Nonetheless, our study is the first to report gaseous and particulate concentrations of FRs in air on a diurnal basis across major cities in Pakistan, offering insights into the atmospheric fate of these substances in urban areas in a sub-tropical region.

Impact of Intravascular Brachytherapy on Patient-Reported Outcomes in Patients with Coronary Artery Disease.

BACKGROUND: Intravascular brachytherapy (VBT) is an established treatment for the management of in-stent restenosis (ISR). However, whether VBT is associated with improved patient reported outcomes unknown. METHODS: We evaluated 51 consecutive patients undergoing VBT in one or more coronary arteries from January 2018 to September 2019. Data on baseline characteristics, procedural outcomes and adverse events were obtained. All patients completed the Seattle Angina Questionnaire - 7 (SAQ-7) form before and after VBT at 1 month and 6 months. RESULTS: The mean age was 69 ± 9 years and 29 (57%) of patients were males. Procedural success was 94.1%. The mean summary SAQ-7 score improved significantly (53.2 ± 21 vs. 83 ± 19, p < .001) at 30-days. The median Quality of Life (QoL) component of SAQ-7 score was 31.3 (Interquartile Range [IQR]: 18.8, 62.5) and improved to 82.5 (IQR: 62.5, 100), p < .001 at 30 days and 87.5 [IQR: 75, 100), p < .001 at last follow up. Likewise, the median angina frequency component of the SQL-7 score pre-VBT was 55 (IQR: 45, 80) and improved significantly to 90 (IQR: 60, 100) at 30-days, p < .001 and 100 [IQR: 68.8, 100], p = .02 at last follow up. Lastly, the median activity component of the SAQ-7 score improved from 83.3 (IQR: 60-100) to 100 (IQR: 83, 100), p = .01 at 30-days. Thus, results were evident as early as 1 month and sustained at median follow up of 17 months. CONCLUSION: VBT is associated with improvement in patient reported outcome measures at short term and long term follow up.

Central Role for Adipocyte Na,K-ATPase Oxidant Amplification Loop in the Pathogenesis of Experimental Uremic Cardiomyopathy.

BACKGROUND: Oxidative stress in adipocyte plays a central role in the pathogenesis of obesity as well as in the associated cardiovascular complications. The putative uremic toxin indoxyl sulfate induces oxidative stress and dramatically alters adipocyte phenotype in vitro. Mice that have undergone partial nephrectomy serve as an experimental model of uremic cardiomyopathy. This study examined the effects on adipocytes of administering a peptide that reduces oxidative stress to the mouse model. METHODS: A lentivirus vector introduced the peptide NaKtide with an adiponectin promoter into the mouse model of experimental uremic cardiomyopathy, intraperitoneally. Then adipocyte-specific expression of the peptide was assessed for mice fed a standard diet compared with mice fed a western diet enriched in fat and fructose. RESULTS: Partial nephrectomy induced cardiomyopathy and anemia in the mice, introducing oxidant stress and an altered molecular phenotype of adipocytes that increased production of systemic inflammatory cytokines instead of accumulating lipids, within 4 weeks. Consumption of a western diet significantly worsened the adipocyte oxidant stress, but expression of NaKtide in adipocytes completely prevented the worsening. The peptide-carrying lentivirus achieved comparable expression in skeletal muscle, but did not ameliorate the disease phenotype. CONCLUSIONS: Adipocyte-specific expression of NaKtide, introduced with a lentiviral vector, significantly ameliorated adipocyte dysfunction and uremic cardiomyopathy in partially nephrectomized mice. These data suggest that the redox state of adipocytes controls the development of uremic cardiomyopathy in mice subjected to partial nephrectomy. If confirmed in humans, the oxidative state of adipocytes may be a therapeutic target in chronic renal failure.

The Na/K-ATPase α1 and c-Src form signaling complex under native condition: A crosslinking approach.

The protein-protein interactions amongst the Na/K-ATPase α1 subunit, c-Src, and caveolin-1 (cav-1) are essential for the Na/K-ATPase signaling functions. However, there are arguments concerning the interaction model. The present study aims to clarify the interactions amongst the endogenous native proteins in live cells under native resting condition. Under native condition, Blue Native-PAGE and Blue Native-PAGE/SDS-PAGE 2D analyses demonstrated co-existence of the α1 subunit and c-Src in same protein complex, as well as a direct interaction between the α1 subunit and c-Src. By comparison of cleavable and non-cleavable cysteine-cysteine crosslinked samples, capillary immunoblotting analysis demonstrated that depletion of Src kinase family members (c-Src, Yes, and Fyn) or cav-1 clearly reduced the interactions of the α1 subunit with proteins, but depletion of cav-1 did not affect the interaction of c-Src with the α1 subunit. The data indicated that there are direct interactions between the α1 subunit and c-Src as well as between the α1 subunit and cav-1, but argued about the interaction between c-Src and cav-1 under the condition. Furthermore, the data also indicated the existence of different protein complexes containing the α1 subunit and c-Src, which might have different signaling functions.

Comparison between sentinel lymph node hybrid scintigraphy and blue dye technique in breast cancer patients: An institutional experience.

To compare the detection efficacy of radionuclide lymphoscintigraphy (LS) versus patent blue dye (PBD) technique for hidden sentinel lymph node (SLN) in breast cancer patients and to determine which modality is better for SLN detection. One hundred and thirty-four early stage breast cancer female patients with clinically negative axilla who underwent post technetium-99m nanocolloid injection single photon emission computed tomography (SPECT-CT) for negative SLN on planar imaging were studied prospectively between 2015 and 2017. Following SPECT-CT, patients underwent peroperative gamma probe count detection GP-CD and PBD technique. Visually, blue stained ± hot nodes were surgically removed and subjected to histopathological analysis. The detection rate by individual method was calculated. Kappa statistics were applied to calculate overall agreement between radioisotope and PBD techniques for diagnostic value assessment. One hundred and thirty-four patients underwent SPECT-CT LS and PBD injection. Mean age: 47 ± 7.6 years (range: 26-82 years). Forty-nine (36.6%) had T1 and 85 (63.4%) T2. SPECT-CT LS detected SLN in 105/134 cases (success rate: 78.4%), later GP-CD localized "hot nodes" in additional 20 cases (success rate: 93.3%). The PBD successfully localized SLN in 131/134 (97.8%) cases. Three cases remained negative on both radioisotope and PBD localization, which on subsequent nodal dissection had metastatic disease. All SLNs detected on SPECT-CT showed blue dye uptake. In 112 cases, more than one SLN was surgically removed. Frozen section analysis of excised SLNs showed metastasis in 31%. Overall moderate agreement (k = 0.56) was calculated. No statistically significant difference was seen between isotope detection and PBD. Radionuclide sentinel mapping has good detection rate particularly combined with peroperative GP-CD. The PBD has added value to reduce false-negative rate of SLN mapping and can substitute radionuclide imaging with negative results.

The Redox-Sensitive Na/K-ATPase Signaling in Uremic Cardiomyopathy.

In recent years, Na/K-ATPase signaling has been implicated in different physiological and pathophysiological conditions, including cardiac hypertrophy and uremic cardiomyopathy. Cardiotonic steroids (CTS), specific ligands of Na/K-ATPase, regulate its enzymatic activity (at higher concentrations) and signaling function (at lower concentrations without significantly affecting its enzymatic activity) and increase reactive oxygen species (ROS) generation. On the other hand, an increase in ROS alone also regulates the Na/K-ATPase enzymatic activity and signaling function. We termed this phenomenon the Na/K-ATPase-mediated oxidant-amplification loop, in which oxidative stress regulates both the Na/K-ATPase activity and signaling. Most recently, we also demonstrated that this amplification loop is involved in the development of uremic cardiomyopathy. This review aims to evaluate the redox-sensitive Na/K-ATPase-mediated oxidant amplification loop and uremic cardiomyopathy.

How Clinically Efficient Is Lumacaftor/Ivacaftor for Cystic Fibrosis Patients? An Updated Literature Review.

Cystic fibrosis (CF) is an autosomal recessive illness caused by the defective cystic fibrosis transmembrane conductance regulator (CFTR) gene. These patients suffer from repeated chronic sinuses and lung infections, resulting in frequent hospital admissions and antibiotic (Abx) courses. These are the major contributing factors responsible for a low health-related quality of life (HRQoL) and increasing the disease burden. The introduction and approval of CFTR modulators-lumacaftor (LUM) and ivacaftor (IVA) in 2015 by the US Food and Drug Administration (FDA) reduced the mortality and morbidity rates associated with the disease. In 2018, the FDA approved these drugs from age two and five years with two copies of F5806 del. This literature review aims to present the studies centered on the clinical effects of LUM/IVA. We searched for the relevant articles, from 2016 to 2020, in PubMed Central (PMC), Google Scholars, and Journal of Cystic Fibrosis. LUM/IVA has a broader range of effects. They showed marked improvement in the reduction of pulmonary exacerbations (PEx), Hospitalization rates, Abx use, and modification in forced expiratory volume in one second (FEV1) status of pre-existing severe lung disease. Now, there is a need for an initiative to conduct more clinical trials and studies in the future to assess and evaluate the long-term clinical benefits and safety of LUM/IVA therapy in all age groups.

Impacts of intake of bakery food chemicals, degraded water and psychiatric drugs on liver & renal functions of brain tumor patients.

A chemically preserved food has raised mental health issues. Abnormalities in liver and kidney functions have been reported from mentally imbalanced individuals. This study was focused on finding anxiety issues and biochemistry alterations in brain tumor patients and in controls. The levels of liver & kidney enzymes were compared in both groups through Mann-Whitney U test. Kendall's tau-b correlation was conducted to determine that is there any relationship between anxiety levels and biochemistry parameters in both groups. There was more occurrence of severe anxiety levels (58%) in brain tumor patients. There were more mood swings in CG (64%) as compared to BP (48%). Less sleeping pattern was found in CG (42%) as compared to BP (37%). More patients (58%) were having severe anxiety levels as compared to CG (52%). 73% patients were having low levels of alkaline phosphatase (AP). 52% individuals in CG were having low levels of AP. AP was found significantly associated with anxiety levels in brain tumor patients only. A nutrient deprived food from preservation can reduce levels of alkaline phosphatase. This can impact metabolism of necessary minerals for proper brain function. This epidemiological study reports a significant association between anxiety and reduced AP levels.