The Biochemistry and Physiology of A Disintegrin and Metalloproteinases (ADAMs and ADAM-TSs) in Human Pathologies.

Metalloproteinases are a group of proteinases that plays a substantial role in extracellular matrix remodeling and its molecular signaling. Among these metalloproteinases, ADAMs (a disintegrin and metalloproteinases) and ADAM-TSs (ADAMs with thrombospondin domains) have emerged as highly efficient contributors mediating proteolytic processing of various signaling molecules. ADAMs are transmembrane metalloenzymes that facilitate the extracellular domain shedding of membrane-anchored proteins, cytokines, growth factors, ligands, and their receptors and therefore modulate their biological functions. ADAM-TSs are secretory, and soluble extracellular proteinases that mediate the cleavage of non-fibrillar extracellular matrix proteins. ADAMs and ADAM-TSs possess pro-domain, metalloproteinase, disintegrin, and cysteine-rich domains in common, but ADAM-TSs have characteristic thrombospondin motifs instead of the transmembrane domain. Most ADAMs and ADAM-TSs are activated by cleavage of pro-domain via pro-protein convertases at their N-terminus, hence directing them to various signaling pathways. In this article, we are discussing not only the structure and regulation of ADAMs and ADAM-TSs, but also the importance of these metalloproteinases in various human pathophysiological conditions like cardiovascular diseases, colorectal cancer, autoinflammatory diseases (sepsis/rheumatoid arthritis), Alzheimer's disease, proliferative retinopathies, and infectious diseases. Therefore, based on the emerging role of ADAMs and ADAM-TSs in various human pathologies, as summarized in this review, these metalloproteases can be considered as critical therapeutic targets and diagnostic biomarkers.

An investigation of the environmental implications of bioplastics: Recent advancements on the development of environmentally friendly bioplastics solutions.

The production and utilization of plastics may prove beneficial, but the environmental impact suggests the opposite. The single-use plastics (SUP) and conventional plastics are harmful to the environment and need prompt disposal. Bioplastics are increasingly being considered as a viable alternative to conventional plastics due to their potential to alleviate environmental concerns such as greenhouse gas emissions and pollution. However, the previous reviews revealed a lack of consistency in the methodologies used in the Life Cycle Assessments (LCAs), making it difficult to compare the results across studies. The current study provides a systematic review of LCAs that assess the environmental impact of bioplastics. The different mechanical characteristics of bio plastics, like tensile strength, Young's modulus, flexural modulus, and elongation at break are reviewed which suggest that bio plastics are comparatively much better than synthetic plastics. Bioplastics have more efficient mechanical properties compared to synthetic plastics which signifies that bioplastics are more sustainable and reliable than synthetic plastics. The key challenges in bioplastic adoption and production include competition with food production for feedstock, high production costs, uncertainty in end-of-life management, limited biodegradability, lack of standardization, and technical performance limitations. Addressing these challenges requires collaboration among stakeholders to drive innovation, reduce costs, improve end-of-life management, and promote awareness and education. Overall, the study suggests that while bioplastics have the potential to reduce environmental impact, further research is needed to better understand their life cycle and optimize their end-of-life (EoL) management and production to maximize their environmental benefits.

Double blind randomized controlled trial of efficacy of ormeloxifene for the treatment of fibroadenoma (The FIBROCENT study).

BACKGROUND: We evaluated the effectiveness of Ormeloxifene (Centchroman) on regression of Fibroadenoma in a double-blind randomized controlled trial. METHODS: Patients with biopsy proven Fibroadenoma were enrolled between March 2023 and October 2023 and divided in two arms- Ormeloxifene group and Placebo group. Effectiveness of the treatment was evaluated using USG. No residual mass was defined as complete regression and more than 30% decrease in size was considered as partial regression. RESULTS: A total of 130 consecutive patients with Fibroadenoma were randomized to Ormeloxifene group (n = 65) and Placebo Group (n = 65). Complete regression was observed in 9% (6/65) patients in Ormeloxifene group and 10.8% (7/65) in Placebo Group at the end of 12 weeks (p = 0.49). Twenty one patients taking Ormeloxifene reported adverse events as compared to none in the other group. CONCLUSION: In our study Ormeloxifene was not found to be effective in treatment of fibroadenoma and had concerning side effects.

What is the Long-term Wear of a 5-Mrad Highly Crosslinked Polyethylene Liner? A 14-year RSA Study.

BACKGROUND: Lower doses of irradiation (≤ 5 Mrad) during the manufacture of highly crosslinked polyethylene acetabular liners may result in less crosslinking and an increased wear rate. Radiostereometric analysis (RSA) studies have found that wear of more highly irradiated highly crosslinked polyethylene liners (7 to 10 Mrad) decreases at longer-term follow-up compared with earlier reports of the same cohorts. Although wear of 5-Mrad irradiated liners appears to increase at midterm follow-up, it is unclear whether that remains true at longer follow-up. QUESTIONS/PURPOSES: We asked: (1) In patients who underwent THA with a 5-Mrad highly crosslinked polyethylene liner, what is the wear rate evaluated with RSA during the first 14 years? (2) Does the wear rate decrease after 6 years in situ? METHODS: This is a brief follow-up of prior RSA studies performed at 2 and 6 years. We prospectively reviewed the longer-term wear rate in 13 patients who underwent primary THAs with the same design of a 5-MRad irradiated crosslinked acetabular liner and a 28-mm cobalt-chromium articulation. Of the initial 30 patients who were enrolled, 13 (43%) were available at the 14-year timepoint; nine patients had died, 1 patient had withdrawn, 1 had an intraoperative fracture, 3 patients were too infirm to have radiographs, 2 had no baseline RSA radiographs, and 1 had poor-quality RSA images. Tantalum markers were inserted during surgery, and all patients had RSA radiographic examinations at 1 week, 6 months, and 1, 2, 6, and 14 years postoperatively. RESULTS: The mean ± standard deviation proximal, 2D, and 3D wear rates calculated between 1 year and 14 years were 0.019 ± 0.013 mm, 0.022 ± 0.015 mm, and 0.025 ± 0.019 mm per year, respectively. No patient had proximal 2D or 3D wear rates exceeding 0.06 mm per year. An increasing wear rate over time was measured for proximal and 2D wear rates between 6 and 14 years (0.024 and 0.030 mm per year) compared with that between 1 and 6 years (0.008 and 0.010 mm per year; p = 0.03). CONCLUSION: The proximal, 2D, and 3D wear of a highly crosslinked polyethylene liner produced using 5-Mrad radiation remains low in the longer-term. With the small numbers available in a long-term RSA study such as this, we confirmed that the wear rate did not decrease at longer-term follow-up, unlike previous RSA studies of more highly irradiated highly crosslinked polyethylene liners. Nevertheless, the wear rate remains very low and below the threshold typically associated with the development of osteolysis (0.1 mm/year of wear). This should provide assurance to orthopaedic surgeons monitoring patients with this 5-Mrad irradiated liner in situ, while providing useful information to manufacturers of future highly crosslinked polyethylene liners. LEVEL OF EVIDENCE: Level IV therapeutic study.

Role of palliative SBRT in barcelona clinic liver cancer-stage C hepatocellular carcinoma patients.

OBJECTIVE: To evaluate the role of palliative stereotactic body radiation therapy (SBRT) in Barcelona Clinic Liver Cancer stage­C (BCLC-C) hepatocellular carcinoma (HCC) patients who are not suitable for other loco-regional therapies. MATERIALS AND METHODS: It is an observational retrospective study done between May 2020 and September 2021. The data were collected from 35 patients of advanced HCC who underwent SBRT. Patients of Child Pugh status (CPs) A5-B7 and with a liver reserve of ≥ 700cc were included. Local control (LC), overall survival (OS) and adverse events including decompensation were carefully recorded. RESULTS: In the cohort, Portal vein and IVC tumor thrombosis were present in 33 (94.3%) and 8 (22.85%) patients, respectively. Lung and nodal metastasis were found in 11 (31.4%) and 21 (60%) of patients, respectively. The median gross tumor volume (GTV) was 563cc (range 80-1925cc). The median SBRT dose prescription was 35 Gy (range 25-40 Gy) in 5-10 fractions. Post radiation therapy, there was improvement in pain and discomfort in 24 out of 29 (82.75%) and 18 out of 23 (78%) patients respectively. Also bone metastasis related pain was improved in all 3 (100%) patients. One year LC, and OS were 80% and 30% respectively. On multivariate analysis, the GTV volume > 750cc and PIVKA-II > 8000 mAU/ml remained the predictor factor for poor OS. Post SBRT, change in child-pugh score by 1 point was observed in 7 patients (20%) which was managed conservatively. CONCLUSION: SBRT is a safe and feasible option for BCLC­C HCC. It not only improves the quality of life by symptom control but also results in good LC and OS with acceptable toxicity. SBRT should be considered in a multidisciplinary fashion for patients presenting with advanced HCCs.

Quest for Active Species in Al/B-Catalyzed CO2 Hydrosilylation.

We demonstrate the catalytic role of aluminum and boron centers in aluminum borohydride [(2-Me2CH2C6H4)(C6H5)Al(µ-H)2B(C6H5)2] (6) during carbon dioxide (CO2) hydrosilylation. Preliminary investigations into CO2 reduction using [(2-Me2NCH2C6H4)(H)Al(µ-H)]2 (1) and [Ph3C][B(3,5-C6H3Cl2)4] (2) in the presence of Et3SiH and PhSiH3 resulted in CH2(OSiR3)2 and CH3OSiR3, which serve as formaldehyde and methanol surrogates, respectively. In pursuit of identifying the active catalytic species, three compounds, B(3,5-C6H3Cl2)3 (3), [(2-Me2NCH2C6H4)(3,5-C6H3Cl2)Al(µ-H)2B(3,5-C6H3Cl2)2] (4), and [(2-Me2NCH2C6H4)2Al(THF)][B(3,5-C6H3Cl2)4] (5), were isolated. Among compounds 2-5, the highest catalytic conversion was achieved by 4. Further, 4 and 6 were prepared in a straightforward method by treating 1 with 3 and BPh3, respectively. 6 was found to be in equilibrium with 1 and BPh3, thus making the catalytic process of 6 more efficient than that of 4. Computational investigations inferred that CO2 reduction occurs across the Al-H bond, while Si-H activation occurs through a concerted mechanism involving an in situ generated aluminum formate species and BPh3.

Prospective randomised phase II trial evaluating adjuvant pelvic radiotherapy using either IMRT or 3-Dimensional planning for endometrial cancer.

OBJECTIVE: To compare the incidence of grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity for patients undergoing 3DRT versus IMRT in the postoperative setting for endometrial cancer. METHODS: Eligible patients were post-operatively randomly assigned to one of two parallel groups in a 1:1 ratio, to have their RT delivered using either a 3DRT technique or using IMRT. The prescription dose was 45 Gy in 25 fractions over 5 weeks followed by vaginal vault brachytherapy. Toxicity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 3.0. Fisher's exact tests were used to test for associations between toxicity and arm. Differences in dosimetric parameters for patients with or without toxicity were tested using Mann-Whitney U-tests. RESULTS: 84 patients with a median age of 62 were evaluable for primary outcome. The median follow-up was 52 months. 14 (35%) participants from the 3DRT arm and 15 (34%) from the IMRT arm experienced acute grade ≥2 GI toxicity with older patients having a statistically higher risk of grade ≥2 acute GI toxicity. 20 (50%) participants from the 3DRT arm and 25 (57%) from the IMRT arm experienced acute grade ≥2 GI or GU toxicity (p = .662). 12 (30%) patients from the 3DRT arm and 17 (39%) from the IMRT arm experienced acute grade ≥2 GU toxicity (p = .493). CONCLUSION: Although IMRT can reduce dose to normal tissue, in this study no benefit in acute GI or GU toxicity outcome was seen.

Engineering nucleosomes for generating diverse chromatin assemblies.

Structural characterization of chromatin is challenging due to conformational and compositional heterogeneity in vivo and dynamic properties that limit achievable resolution in vitro. Although the maximum resolution for solving structures of large macromolecular assemblies by electron microscopy has recently undergone profound increases, X-ray crystallographic approaches may still offer advantages for certain systems. One such system is compact chromatin, wherein the crystalline state recapitulates the crowded molecular environment within the nucleus. Here we show that nucleosomal constructs with cohesive-ended DNA can be designed that assemble into different types of circular configurations or continuous fibers extending throughout crystals. We demonstrate the utility of the method for characterizing nucleosome compaction and linker histone binding at near-atomic resolution but also advance its application for tackling further problems in chromatin structural biology and for generating novel types of DNA nanostructures. We provide a library of cohesive-ended DNA fragment expression constructs and a strategy for engineering DNA-based nanomaterials with a seemingly vast potential variety of architectures and histone chemistries.

The Role of Monocyte to High-density Lipoprotein Cholesterol Ratio in Predicting the Severity of Acute Ischemic Stroke and its Association with the NIHSS.

BACKGROUND: Atherosclerosis, an underlying abnormality, plays a significant role in the progression of ischemic stroke. Inflammation, oxidative stress, platelet activation, endothelial dysfunction, and lipid abnormalities are the primary factors involved in the development of atherosclerosis. Monocytes, key contributors to chronic inflammation, actively participate in the development, progression, and rupture of atherosclerotic plaques within blood vessels. Therefore, the objective of this study is to investigate the monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) in acute ischemic stroke (AIS) and its correlation with the National Institute of Health Stroke Scale (NIHSS) to predict the severity of the condition. MATERIALS AND METHODS: A prospective observational study was conducted on 100 AIS patients and age/gender-matched controls at a hospital in Kota. Diagnostic methods included clinical examination, imaging, and laboratory tests. MHR was measured using a hematology analyzer and correlated with reference values and stroke severity. RESULTS: The mean MHR of AIS patients were higher (14.12 ± 2.95) than controls (7.09 ± 1.48) (p = 0.0001). Besides, a statistically significant positive correlation was obtained between his MHR and NIHSS scores at admission and discharge. MHR values were significantly greater from a reference point in patients who deteriorated (18.48 ± 4.02) compared to significantly lower values in patients who improved (13.66 ± 2.44). CONCLUSION: In our study, the MHR shows an increased value in patients with AIS, and a linear correlation is found with the NIHSS score. Thus, the method is a pocket-friendly, easily available, and simple-to-use novel inflammatory marker that may predict the severity of a disease.

To Study Mean Corpuscular Volume in Alcoholic Liver Disease Patients and to Compare with Child-Pugh Score to Predict the Severity.

INTRODUCTION: Liver injury caused by the alcohol abuse is called alcoholic liver disease (ALD). In particular, ethanol exposure induces cell membrane remodeling in different cells and lipid vesicles including membrane fluidization. These phenomena may be related to the effects of alcohol on the red blood cells (RBCs) membrane because unmetabolized ethanol can have a direct effect on membrane properties. MATERIALS: It was a cross sectional study conducted in 50 adult patients of both sex with a diagnosis of alcoholic liver disease and equal number of controls matched in age and sex. Blood sample collected at the time of admission and sent for investigations and child-pugh score calculated. RESULT: Maximum number of subjects were in 30 to 50 years of age group. Mean value of MCV in patients with alcoholic liver disease was 99.7fl (±8.176) and in control group was 84.2fl (±10.58) (P = 0.0001). Patients in child-pugh class A, B and C were 14%, 62% and 24% respectively. Moreover, there was statistically significant, positive correlation between MCV and child-pugh score. The raised MCV in alcoholic liver disease patients was associated with severity of ALD as mean MCV was 92.28 fl (±2.81) (P = 0.001) in child-pugh class A, 96.22fl (±8.20) (P = 0.001) in child-pugh class B and 113 fl (±11.25) (P = 0.005) in child-pugh class C. CONCLUSION: Mean corpuscular volume is a simple, cost effective and easily obtainable test that may help in predicting the severity of disease and prognosis in terms of life expectancy as evidenced by its increased value in patients of chronic liver disease as well as its linear positive correlation with child-pugh score.

The Role of Absolute Eosinophil Count as a Diagnostic and Prognostic Marker for Sepsis and Its Relation with Sequential Organ Failure Assessment/Quick Sequential Organ Failure Assessment Score.

AIMS AND BACKGROUND: Sepsis is a dysregulated host response to an infection that causes organ failure that poses a serious risk to life. Although culture results are not always available right away and the majority of patients continue to test culture negative, microbial culture is still the gold standard for diagnosing sepsis. Therefore, the objective of the current study was to assess absolute eosinophil count as a new marker for diagnosing sepsis and also to assess the prognosis of the patient in relation to Sequential Organ Failure Assessment (SOFA)/quick Sequential Organ Failure Assessment (qSOFA) score. Resources and procedures: In this cross-sectional study, 100 patients with sepsis were enrolled. The other 100 patients without any evidence of sepsis were taken as controls. Absolute eosinophil count (AEC), SOFA/qSOFA scores of all the patients were measured on the 1st, 3rd, and 7th day and data was analyzed statistically. RESULTS: The mean AEC on admission day in sepsis patients was 49.5. The mean AEC among survivors was >50 and nonsurvivors was <50. AEC and SOFA/qSOFA scores exhibit a statistically significant and inverse correlation on the 1st, 3rd, and 7th day of illness. CONCLUSION: Absolute eosinophil count (AEC) is a simple and cost-effective marker that may be helpful in diagnosis as well as in predicting the prognosis of sepsis as evidenced by its linear inverse correlation with SOFA/qSOFA score.

Validation sentinel lymph node biopsy study in cN0 axilla using low-cost dual dye technique: potential solution for resource poor settings.

BACKGROUND: Sentinel lymph node biopsy (SLNB) using radio-pharmaceutical and a blue dye is gold standard for axillary staging in clinically node-negative breast cancer. High costs and limited availability of radio-pharmaceutical and/or gamma probe are major deterrents in performing SLNB in developing countries. In this study, we evaluated feasibility of SLN identification (SLN-IR) of fluorescein-guided (FG) SLNB in combination with methylene blue dye (MBD). METHODS: This was a prospective cross-sectional non-randomized validation study in patients with clinically node-negative axilla. Patients underwent validation SLNB using fluorescein (and blue LED light) and MBD. Axillary dissection was performed irrespective of SLNB histology. SLIN-IR and False Negative Rate (FNR) were assessed for both groups. RESULTS: The SLNs were identified in 29 (96.6%) pre-chemotherapy patients and 23 (82%) post Neoadjuvant Chemotherapy (NACT) patients. The median number of sentinel lymph nodes identified was 3 (range of 1-5) in pre-chemotherapy patients and 1 (range of 1-3) in post NACT patients. The SLN-IR using MBD was 90%, FD was 86.7% and combined MBD FD was 96.7% in pre-chemotherapy patients. The SLN-IR using MBD was 82%, FD was 71% and combined MBD FD was 82% in in post NACT patients. The false negative rate (FNR) in pre-chemotherapy group was 8.0% (MBD), 8.3% (FD) and 7.4% (MBD + FD). The FNR in post NACT group was 8.7% (MBD), 10% (FD) and 8.7% (MBD + FD). CONCLUSION: This prospective validation study showed adequate SLN-IR and FNR using low-cost dual dyes in early breast cancer patients and can be used in low resource settings. However, SLNB in post NACT axilla though viable along with a satisfactory FNR, is associated with low identification rate and needs further evaluation.

Acute C-Terminal Crosslinking Telopeptide of Type I Collagen (CTX-1) Suppression with Milk Calcium or Calcium Carbonate Is Independent of Visceral Fat in a Randomized Crossover Study in Lean and Overweight Postmenopausal Women.

BACKGROUND: Postmenopausal women with higher visceral adipose tissue (VAT) present with suppressed bone resorption (lower C-terminal crosslinking telopeptide of type I collagen; CTX-1) and turnover (lower osteocalcin) but whether this blunts the effect of calcium is unknown. OBJECTIVES: The primary outcome of this study was the effect of VAT on changes in CTX-1 after intake of 2 forms of calcium. Secondary outcomes included changes in parathyroid hormone (PTH), serum calcium, phosphorus, and alkaline phosphatase (ALP). METHODS: Randomized open three period crossover trial conducted between 2017 and 2019 at the University of South Australia among 77 lean and overweight postmenopausal women (53-79 y) with BMI <25 kg/m2 and >27 kg/m2, respectively. Participants received a single dose of milk (1000 mg calcium), calcium carbonate tablet (1000 mg calcium), and fruit juice (no calcium) in random order with a 7-d washout period. Blood samples were collected at baseline and hourly for 5 h. Data was analyzed by repeated measures ANOVA of log-transformed data. RESULTS: At baseline, women with higher VAT had significantly lower CTX-1 and higher PTH (44% lower and 30% higher, respectively, between Q4 and Q1, P < 0.0001). VAT had no influence on the acute changes in CTX-1 or PTH with calcium or juice. A suppression of 44% in CTX-1 was seen with calcium carbonate and milk and a suppression of 18% with juice. PTH was suppressed more with calcium carbonate (47%) compared to milk (22%). Milk calcium reduced PTH and CTX-1 at 2 h, whereas calcium carbonate reduced PTH in 1 h. The suppression in CTX-1 was slower with lowest concentrations at 4-5 h. CONCLUSIONS: Intake of 1000 mg calcium from milk or from calcium carbonate is effective in acutely suppressing bone resorption in postmenopausal women irrespective of visceral fat. This trial is registered at http://www.ANZCTR.org.au/ACTRN12617000779370.aspx as ACTRN 12617000779370).

Acute C-Terminal Crosslinking Telopeptide of Type I Collagen (CTX-1) Suppression with Milk Calcium or Calcium Carbonate Is Independent of Visceral Fat in a Randomized Crossover Study in Lean and Overweight Postmenopausal Women.

BACKGROUND: Postmenopausal women with higher visceral adipose tissue (VAT) present with suppressed bone resorption (lower C-terminal crosslinking telopeptide of type I collagen; CTX-1) and turnover (lower osteocalcin) but whether this blunts the effect of calcium is unknown. OBJECTIVES: The primary outcome of this study was the effect of VAT on changes in CTX-1 after intake of 2 forms of calcium. Secondary outcomes included changes in parathyroid hormone (PTH), serum calcium, phosphorus, and alkaline phosphatase (ALP). METHODS: Randomized open three period crossover trial conducted between 2017 and 2019 at the University of South Australia among 77 lean and overweight postmenopausal women (53-79 y) with BMI <25 kg/m2 and >27 kg/m2, respectively. Participants received a single dose of milk (1000 mg calcium), calcium carbonate tablet (1000 mg calcium), and fruit juice (no calcium) in random order with a 7-d washout period. Blood samples were collected at baseline and hourly for 5 h. Data was analyzed by repeated measures ANOVA of log-transformed data. RESULTS: At baseline, women with higher VAT had significantly lower CTX-1 and higher PTH (44% lower and 30% higher, respectively, between Q4 and Q1, P < 0.0001). VAT had no influence on the acute changes in CTX-1 or PTH with calcium or juice. A suppression of 44% in CTX-1 was seen with calcium carbonate and milk and a suppression of 18% with juice. PTH was suppressed more with calcium carbonate (47%) compared to milk (22%). Milk calcium reduced PTH and CTX-1 at 2 h, whereas calcium carbonate reduced PTH in 1 h. The suppression in CTX-1 was slower with lowest concentrations at 4-5 h. CONCLUSIONS: Intake of 1000 mg calcium from milk or from calcium carbonate is effective in acutely suppressing bone resorption in postmenopausal women irrespective of visceral fat. This trial is registered at http://www.ANZCTR.org.au/ACTRN12617000779370.aspx as ACTRN 12617000779370).

Bioengineered 3D microfibrous-matrix modulates osteopontin release from MSCs and facilitates the expansion of hematopoietic stem cells.

The osteopontin (OPN) released from mesenchymal stem cells (MSCs) undergoing lineage differentiation can negatively influence the expansion of hematopoietic stem cells (HSCs) in coculture systems developed for expanding HSCs. Therefore, minimizing the amount of OPN in the coculture system is important for the successful ex vivo expansion of HSCs. Toward this goal, a bioengineered three dimensional (3D) microfibrous-matrix that can maintain MSCs in less OPN-releasing conditions has been developed, and its influence on the expansion of HSCs has been studied. The newly developed 3D matrix significantly decreased the release of OPN, depending on the MSC culture conditions used during the priming period before HSC seeding. The culture system with the lowest amount of OPN facilitated a more than 24-fold increase in HSC number in 1 week time period. Interestingly, the viability of expanded cells and the CD34+   pure population of HSCs were found to be the highest in the low OPN-containing system. Therefore, bioengineered microfibrous 3D matrices seeded with MSCs, primed under suitable culture conditions, can be an improved ex vivo expansion system for HSC culture.

Oral toxicity evaluation of gokshuradi guggulu, an ayurvedic formulation.

Gokshuradi guggulu is an important classical polyherbal formulation used in Ayurvedic system of medicine for the treatment of various chronic diseases like kidney stones and diabetes. However, no scientific attempts were made to evaluate its oral toxicity. Hence, the present study evaluated the acute and 28 days repeated dose sub-acute oral toxicities of gokshuradi guggulu in rats. Gokshuradi guggulu was tested for its compliance using physicochemical and analytical parameters as per standards prescribed in Ayurvedic Pharmacopeia of India. In acute oral toxicity study, Wistar rats were orally administered a single dose of gokshuradi guggulu (2700 mg/kg) and clinical signs and mortality or moribund stage were observed for 14 days along with weekly body weight. On day 15, the rats were euthanized and the gross morphology was carried out during necropsy. In sub-acute (repeated dose) oral toxicity study, the rats were orally administered gokshuradi guggulu (270, 1350 and 2700 mg/kg) once daily up to 28 days. Clinical signs and mortality or moribund stage, weekly body weight, weekly feed and water consumptions, biochemical and hematological investigations, urine analysis, and major organ weights and histopathology were carried out. In acute and sub-acute toxicity studies, gokshuradi guggulu administration did not show any alteration in parameters or any adverse effect as compared to vehicle treated group. There was no mortality or moribund state observed in any group in both studies. Administration of gokshuradi guggulu in acute and 28 days repeated doses did not exhibit any toxicity or adverse effect at the doses used and NOAEL was found to be 2700 mg/kg.

To Study Role of Serial Serum Albumin Estimation as Prognostic Marker in Critically Ill Patients.

Albumin is the most abundant plasma protein in humans. It works to maintain the colloid oncotic pressures, acts as a carrier protein, and is involved in metabolism, antioxidant, and various other functions. Patients who are admitted to the Intensive Care Unit (I.C.U.) are at an increased risk of mortality due to the severity of their illness. It is thus, important to identify patients at the time of admission who are likely to have a poor outcome so that such patients can be managed aggressively. Serum Albumin appears to be one such prognostic indicator. Its utility as a prognostic indicator has been studied in various contexts including critically ill patients. A low serum albumin concentration correlates with the increase in length of stay in ICU, increasing the risk of death and frequent readmission. The daily trend of serum albumin can be a useful tool in predicting the weaning capability of patients needing mechanical ventilation. MATERIAL: The study was conducted on 100 adult patients of both sexes who are critically ill admitted in the emergency wards and ICU unit in the GMC Kota were included in the study Inclusion Criteria: Critical ill patients will be defined as those who either have multi-organ dysfunction and/or sepsis, need ventilatory support, and required intensive care. EXCLUSION CRITERIA: Chronic liver failure, Nephrotic syndrome/chronic kidney disease, Protein-losing enteropathy, Chronic malnutrition. OBSERVATION: It was observed during the study that the mean age of the study population was 54.5years. The mean age in survivors was 49.6 years. The mean age in non-survivors was 62.3 years. There was a significant difference (p = 0.0024) between the two groups indicating a higher age at admission for non-survivors. The total decline in serum albumin in the survivors from admission to day10 is 0.75 g/dl. In nonsurvivors, it is 1.07 g/dl over a period of 10 days. The fall in nonsurvivors is steeper than survivors. It suggests that the rapidity with which serum albumin level falls has an effect on the prognosis of the patient in terms of mortality. A steep decline in serum albumin indicates a poor prognosis. CONCLUSION: The result shows that serial measurement of serum albumin can accurately predict the outcome. Survivors had significantly higher serum albumin levels all day compared to non-survivors. Serum albumin is routinely measured in all patients and it is a cheap and easily available test facility in all laboratories.

Role of Platelet to Lymphocyte Ratio (PLR) and its Correlation with NIHSS (National Institute of Health Stroke Scale) for Prediction of Severity in Patients of Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Stroke is the second leading cause of death and third most common cause of disability-adjusted life years in the world. Atherosclerosis plays a key role in the pathogenesis of stroke and inflammation is central in the initiation, progression and complications of atherosclerosis by mediating every stage of atheroma development. High platelet counts may increase thrombocyte activation and aggravate the release of inflammatory mediators. In contrast, lymphocytes exert anti-inflammatory response in atherosclerosis development. The advantage of platelet to lymphocyte ratio (PLR) is that it reflects the condition of both inflammation and thrombosis pathways and is more valuable than either platelet or lymphocyte counts alone. This emerging marker has not been frequently studied with acute ischemic stroke; hence aim of the present study was to find out the role of PLR (Platelet to lymphocyte ratio) in patients of acute ischemic stroke and correlating with NIHSS for predicting the prognosis. MATERIAL AND METHODS: 100 cases of AIS and equal number of age and gender matched control were enrolled in the study. NIHSS score and PLR (from the CBC test) was calculated both at admission and on day 7 or discharge. RESULTS: Maximum subjects in our study were in the age range of 61-70 years with males (69%) outnumbering females (31%). Incidence of hypertension, diabetes mellitus, hyperlipidemia, smoking and alcoholism was more in the cases than controls. Mean PLR was higher in the patients of AIS (235.98±93.92) as compared to control group (115.60±27.87) (p=0.0001). Moreover, there was statistically significant, positive correlation between PLR and NIHSS score both at admission and discharge. PLR value increased significantly from the baseline in patients who deteriorated (263.42±108.98 to 346.28±125.35; p=0.016), decreased drastically in patients who improved (242.27±75.14 to 167.19±57.91; p=0.0001) and did not change much in patients who tend to remain static (181.35±105.40 to 183.36±111.61; p=0.955). CONCLUSION: Platelet to lymphocyte ratio (PLR) is a simple, cost effective and easily obtainable novel inflammatory marker that may help in predicting the severity of disease and prognosis in terms of functional outcome as evidenced by its increased value in patients of acute ischemic stroke as well as its linear positive correlation with NIHSS score.

Carcinogenic risk from exposure to PM2.5 bound polycyclic aromatic hydrocarbons in rural settings.

In the study, first-time personal exposure level of polycyclic aromatic hydrocarbons (PAHs) was measured during cooking hours in participants of three different types of kitchen both in the particulate and gaseous phase using traditional and improved cookstoves. Along with that, indoor particulate matter (PM) concentration was also estimated during the cooking hours to examine the impact of intervention in different kitchens. The results of the study clearly revealed that the kitchen characteristics and type of cookstove technology have a significant impact on PM2.5, PM1 and PAHs concentration. Cookstoves intervention has resulted in maximum reduction of PM1 i.e. 75% in an enclosed kitchen followed by semi-enclosed and open kitchen having 71% and 52%, respectively. In addition, correlation analysis of PM2.5 and PM1 with PAHs showed a strong association (r2 = 0.9), showing the affinity of PAHs to bind to fine range of particles. Health risk assessment was also carried out to assess the PM daily dose and carcinogenic and non-carcinogenic risk due to inhalation of PAHs. The study confirmed the personal concentration of PAHs compounds was significantly high (p < 0.05) during use of traditional cookstove compared to improved cookstove among all the three kitchens. Furthermore, to measure the toxicity levels, PAHs concentrations have been converted to benzo[a]pyrene equivalence for calculating cancer and non-cancer effects using toxicity equivalency factors. The overall lifetime carcinogenic risk was the highest 2.5E-03, 6.4E-04 among women who prepared meals in the enclosed kitchen compared to 8.4E-04, 1.3E-04 in semi-enclosed and 2.2E-04, 4.6E-05 in the open kitchen during use of traditional and improved cookstoves, respectively, which exceeded the US EPA standard i.e. 1 × 10-6. The study underlined the importance of personal monitoring for exposure, and risks-based studies along with the time-activity of user to measure the actual inhalation risk for the participants. These findings indicated that women are exposed to hazardous smoke in the indoor kitchen and are at greater risk of developing cancer, especially in rural areas.

To Study the Role of Absolute Lymphocyte Count and RDW in COVID 19 Patients and their Association with Appearance of Symptoms and Severity.

OBJECTIVE: The present study was undertaken to evaluate prognostic relevance of select circulating immune mechanistic biomarkers in COVID-19 positive patients for early identification and categorization of symptomatic patients who would need critical care with consequent adequate and optimal resource allocation and definitive management protocol. MATERIALS AND METHODS: The present retrospective observational study, on 35 symptomatic and 35 asymptomatic patients, was carried out in SMS Medical College and Hospital, Jaipur comparatively assessing epidemiological history, clinical features and laboratory investigations. RESULTS: During the course of study, 35 symptomatic and 35 asymptomatic patients were assessed. All the patients were of Indian ethnicity and had a history of contact with a COVID 19 positive case. Male patients constituted of 67 % of the population. The median age of patients in symptomatic and asymptomatic group was 60 years and 30 years, respectively. Out of the 70 patients studied, 47 (67%) patients recovered and were discharged whereas 23 (32.8 %) succumbed to the disease process. Lymphopenia was observed in 80% of symptomatic patient population, though only 11.5% of asymptomatic patients documented lymphopenia. Among the patients who died of COVID 19 (n=23), lymphopenia was observed in 18 (82%) patients, with moderate lymphopenia present in 13 (59 %) and severe lymphopenia present in 5 (22.7%) patients. Neutrophilia was observed across both category of patients, symptomatic and asymptomatic. Neutrophilia featured prominently in the symptomatic COVID-19 group with a median nadir in ALC of 7 × 109/L as compared to that of 3.8 × 109/L so observed in asymptomatic sample population. Red cell distribution width was slightly raised in both groups with a median RDW of 15.3% in COVID 19 patients which was raised as compared to that observed in normal population (range: 12.8 ± 1.2 %). CONCLUSION: Lymphopenia is an effective and reliable indicator of onset of symptoms and severity of disease in COVID-19 patients. RDW was found to be higher in COVID 19 patients in comparison to normal patients, however it had no significant relationship with appearance of symptoms or severity of the disease.