Lung Manifestation of Dengue Fever: A Retrospective Study.

Introduction Dengue fever, caused by the dengue virus transmitted by Aedes aegypti mosquitoes, is a significant public health concern globally. Its resurgence in recent years, particularly in low- and middle-income countries, has led to increased morbidity and mortality rates. Atypical manifestations, involving the cardiac, liver, gut, renal, blood, bone, nervous, and respiratory systems, in dengue, can complicate both diagnosis and management. This study aimed to investigate the incidence of lung manifestations in dengue-infected individuals and their correlation with patient outcomes. Background The prevalence of dengue fever has risen dramatically over the past two decades, with Asia bearing the brunt of the burden, particularly India. The pathophysiology of lung complications in dengue remains unclear but is thought to be related to capillary leak syndrome and thrombocytopenia. Studies suggest that respiratory symptoms may be associated with severe cases and increased mortality rates. Despite limited research in India, understanding lung manifestations in dengue is crucial for improving diagnostic accuracy and patient care. Methods A retrospective study was conducted at K.S. Hegde Hospital, a tertiary care facility located in Mangalore, India, involving patients aged 18 years and above diagnosed with dengue fever between January and December 2019. Data gathered comprised patient demographics, clinical symptoms, laboratory findings, imaging results including radiographs, computed tomography (CT) scans of the chest (if accessible), ultrasound examinations of the chest and abdomen, and 2D echocardiograms, as well as patient outcomes. Diagnosis of lung manifestation was established through clinical assessment, chest X-ray interpretation, and ultrasound of the chest. Statistical analysis was conducted using SPSS Statistics (version 20), with a significance set at p<0.05. Results Out of 255 dengue cases, 10.19% (n=26) exhibited pulmonary manifestations, with pleural effusion being the most common. Older age (>50 years) and comorbidities were associated with a higher incidence of lung involvement. Respiratory symptoms, such as breathlessness, were more prevalent in patients with pulmonary complications. Laboratory parameters indicated distinct profiles in patients with lung manifestations, including elevated total count, urea, bilirubin, and liver enzymes, and reduced platelet counts. Mortality rates were higher in patients with lung involvement, older age, and comorbidities. Discussion The study findings highlight the importance of recognizing respiratory symptoms in dengue fever, particularly in older patients and those with underlying health conditions. The association between pulmonary involvement and adverse outcomes underscores the need for early detection and appropriate management strategies. Future research should focus on elucidating the pathophysiology of lung complications in dengue and developing targeted interventions to improve patient outcomes. Conclusion Lung manifestations in dengue fever represent a significant clinical challenge and are associated with increased morbidity and mortality. Early recognition of respiratory symptoms, along with prompt diagnostic evaluation and appropriate management, is essential for improving patient prognosis. Further studies are warranted to deepen our understanding of lung involvement in dengue and optimize therapeutic approaches to mitigate its impact on patient outcomes.

TCAD simulation study of heavy ion radiation effects on hetero junctionless tunnel field effect transistor.

Semiconductor devices used in radiation environment are more prone to degradation in device performance. Junctionless Tunnel Field Effect Transistor (JLTFET) is one of the most potential candidates which overcomes the short channel effects and fabrication difficulties. In this work, 20 nm JLTFET is proposed with Silicon in the drain/channel region whereas source uses different materials, Silicon Germanium (SiGe), Gallium Nitride (GaN), Gallium Arsenide (GaAs), Indium Arsenide (InAs). The device performance is examined by subjecting it to heavy ion radiation at a lower and higher dose of linear energy transfer (LET) values. It can be seen that the most sensitive location is the source/channel (S/C) interface for SiGe, GaN and GaAs whereas the drain/channel (D/C) interface for InAs. Further analysis is carried out at these vulnerable regions by matching ION of all materials. The parameters, transient peak current (Ipeak), collected charge (QC), threshold voltage shift (ΔVth) and bipolar gain (ß) are extracted using transient simulations. It is observed that for a lower dose of LET, Ipeak of SiGe is 27% lesser than InAs and for higher dose of LET, SiGe shows 56% lesser Ipeak than InAs. SiGe is less sensitive at lower and higher dose of LET due to reduced ΔVth, tunneling and electron density.

ABL1 kinase plays an important role in spontaneous and chemotherapy-induced genomic instability in multiple myeloma.

ABSTRACT: Genomic instability contributes to cancer progression and is at least partly due to dysregulated homologous recombination (HR). Here, we show that an elevated level of ABL1 kinase overactivates the HR pathway and causes genomic instability in multiple myeloma (MM) cells. Inhibiting ABL1 with either short hairpin RNA or a pharmacological inhibitor (nilotinib) inhibits HR activity, reduces genomic instability, and slows MM cell growth. Moreover, inhibiting ABL1 reduces the HR activity and genomic instability caused by melphalan, a chemotherapeutic agent used in MM treatment, and increases melphalan's efficacy and cytotoxicity in vivo in a subcutaneous tumor model. In these tumors, nilotinib inhibits endogenous as well as melphalan-induced HR activity. These data demonstrate that inhibiting ABL1 using the clinically approved drug nilotinib reduces MM cell growth, reduces genomic instability in live cell fraction, increases the cytotoxicity of melphalan (and similar chemotherapeutic agents), and can potentially prevent or delay progression in patients with MM.

Thyroid Eye Disease and Its Association With Diabetes Mellitus: A Major Review.

PURPOSE: Thyroid eye disease (TED) associated with diabetes mellitus (DM) presents unique challenges. DM is a risk factor for TED. Standard management of TED with glucocorticoids (GC), orbital radiation, or teprotumumab can cause adverse events in poor glycemic control. The authors reviewed the literature on the relationship between TED and DM and the management of co-existing diseases. METHODS: The authors searched PubMed with keywords "thyroid eye disease," "diabetes mellitus," and similar terms from 2013 to 2022. The authors included relevant studies after screening the abstracts. Additional references to the selected studies were included where applicable. Data were extracted from the final articles according to the preplanned outline of the review. RESULTS: The initial search yielded 279 abstracts. The final review included 93 articles. TED and DM interact at multiple levels-genetic, immunologic, cellular, nutritional, and metabolic. Both DM and thyroid dysfunction exacerbate the morbidity caused by the other. Metabolic factors also affect the inflammatory pathway for TED. Patients with DM develop TED with greater frequency and severity, necessitating interventions for vision salvage. Agents (GC, teprotumumab, or radiation) used for TED are often unsuitable for treatment with DM, especially if there is poor glycemic control or diabetic retinopathy. There were no studies on using steroid-sparing agents in TED with DM. CONCLUSION: TED and DM co-exist because of multiple intersections in the pathophysiology. Challenges in the treatment include increased TED severity and risk of hyperglycemia and retinopathy. Multidisciplinary teams best undertake treatment of TED with DM.

Immunomodulation of NK, NKT and B/T cell subtypes in relapsed/refractory multiple myeloma patients treated with pomalidomide along with velcade and dexamethasone and its association with improved progression-free survival.

Background: Multiple Myeloma (MM) patients exhibit dysregulated immune system, which is further weakened by chemotherapeutic agents. While cereblon-modulating agents, such as pomalidomide and lenalidomide, have been found to improve the immune profile, the efficacy of their impact in combination with other treatments is yet unknown. Methods: We conducted an immune-profiling of a longitudinal cohort of 366 peripheral blood samples from the CC4047-MM-007 (OPTIMISMM, NCT01734928) study. This study followed relapsed/refractory Multiple Myeloma (RRMM) patients who were treated with Velcade + dexamethasone (Vd), or Vd with pomalidomide (PVd). 366 blood samples from 186 patients were evaluated using multi-color flow cytometry at 3 timepoints: screening, day 8 of cycle 1, and cycle 3. Results: Among NK and NKT cell populations, adding pomalidomide showed no inhibition in the frequency of NK cells. When expression of double positivity for activation markers like, p46/NKG2D, on NK cells was higher than the median, PVd treated patients showed significantly better (p=0.05) progression-free survival (PFS) (additional 15 months) than patients with lower than the median expression of p46/NKG2D on NK cells. PVd treated patients who expressed CD158a/b below the median at cycle 1 demonstrated a significantly better PFS (more than 18months). Among B cell subtypes, PVd treatment significantly increased the abundance of B1b cells (p<0.05) and decreased Bregs (p<0.05) at day 8 of both cycle 1 and cycle 3 when compared to screening samples. Of all the B cell-markers evaluated among paired samples, a higher expression of MZB cells at day 8 of cycle 1 has resulted in enhanced PFS in PVd treated patients. Within T cells, pomalidomide treatment did not decrease the frequency of CD8 T cells when compared with screening samples. The higher the surface expression of OX-40 on CD8 T cells and the lower the expression of PD-1 and CD25 on CD4 T cells by PVd treatment resulted in improved PFS. Conclusion: The prognostic significance for the number of immune markers is only seen in the PVd arm and none of these immune markers exhibit prognostic values in the Vd arm. This study demonstrates the importance of the immunomodulatory effects and the therapeutic benefit of adding pomalidomide to Vd treatment.

A Thyrotoxic Periodic Paralysis Case Study: From Weakness to Wellness.

Hypokalaemic periodic paralysis (HPP) is a rare disorder characterized by episodic attacks of muscle weakness and hypokalaemia. Numerous factors contributing to HPP have been identified, encompassing both hereditary and familial origins as well as acquired factors. In this context, we highlight thyrotoxicosis causing HPP. We present a case of a 40-year-old Asian individual who presented with episodes of sudden onset bilateral proximal limb weakness and palpitations. Laboratory investigations revealed severe hypokalaemia (serum potassium: 1.8 mmol/L). Immediate potassium replacement therapy alleviated symptoms. Further evaluation revealed a new diagnosis of hyperthyroidism, with subsequent treatment initiated (carbimazole and propranolol) preventing recurrence of symptoms. This case highlights the importance of recognizing HPP as a potential manifestation of thyroid dysfunction, particularly in individuals of Asian ethnicity.

Transcaruncular medial orbitotomy: A globe sparing intervention in management of COVID associated mucormycosis [CAM].

AIMS: To describe a novel method of transcaruncular medial orbitotomy, local debridement and amphotericin B irrigation into orbit for COVID-19-associated rhino-orbital mucormycosis. Also to evaluate its its outcome in controlling the disease, increasing the survival rate and as a globe-sparing intervention in them. METHODOLOGY: A total of ten COVID-19-associated mucormycosis patients with clinical and radiological evidence of orbital involvement with necrotic tissue localized in medial orbit were considered for our study. A transcaruncular modified medial orbitotomy with medial and inferomedial orbit debridement was done along with placement of scalp vein catheter by a single surgeon. Postoperatively 3.5 mg/ml liposomal amphotericin B irrigation through the catheter was done for 5 sittings. Correction of underlying systemic conditions and intravenous antifungals were given. Clinical response to the procedure was noted on postoperative week 1, week 4, and 3rd month (week 12). RESULTS: The mean age group was noted to be 49.9 years with a male: female ratio of 2.3:1. All patients were diabetics with 5 being newly detected diabetes after COVID infection. All the ten patients showed significant clinical improvement at the first follow-up (week 1). Five patients at 1st month showed clinical and radiological improvement, while one patient had worsening of orbital disease for which exenteration was done. Three patients succumbed to the disease due to altered cardiopulmonary status and 1 patient was lost to follow-up. All 6 survived patients were stable till the last follow-up. Hence, mortality rate accounted to 30% and globe survival of 40% in the current study. CONCLUSION: Transcaruncular approach to orbit for adequate debridement combined with amphotericin irrigation is a novel technique that can be considered for compartmental involvement of orbit in mucormycosis. Debridement removes the necrotic tissue, while local amphotericin irrigation directly reaches the target tissues that effectively halts the disease progression and hence can be considered an effective globe-sparing intervention without affecting the disease outcome.

South Asian medical cohorts reveal strong founder effects and high rates of homozygosity.

The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of rare homozygotes that reach 100 times that seen in outbred populations. Founder effects increase the power to associate functional variants with disease processes and make South Asia a uniquely powerful place for population-scale genetic studies.

Elevated APE1 Dysregulates Homologous Recombination and Cell Cycle Driving Genomic Evolution, Tumorigenesis, and Chemoresistance in Esophageal Adenocarcinoma.

BACKGROUND & AIMS: The purpose of this study was to identify drivers of genomic evolution in esophageal adenocarcinoma (EAC) and other solid tumors. METHODS: An integrated genomics strategy was used to identify deoxyribonucleases correlating with genomic instability (as assessed from total copy number events in each patient) in 6 cancers. Apurinic/apyrimidinic nuclease 1 (APE1), identified as the top gene in functional screens, was either suppressed in cancer cell lines or overexpressed in normal esophageal cells and the impact on genome stability and growth was monitored in vitro and in vivo. The impact on DNA and chromosomal instability was monitored using multiple approaches, including investigation of micronuclei, acquisition of single nucleotide polymorphisms, whole genome sequencing, and/or multicolor fluorescence in situ hybridization. RESULTS: Expression of 4 deoxyribonucleases correlated with genomic instability in 6 human cancers. Functional screens of these genes identified APE1 as the top candidate for further evaluation. APE1 suppression in EAC, breast, lung, and prostate cancer cell lines caused cell cycle arrest; impaired growth and increased cytotoxicity of cisplatin in all cell lines and types and in a mouse model of EAC; and inhibition of homologous recombination and spontaneous and chemotherapy-induced genomic instability. APE1 overexpression in normal cells caused a massive chromosomal instability, leading to their oncogenic transformation. Evaluation of these cells by means of whole genome sequencing demonstrated the acquisition of changes throughout the genome and identified homologous recombination as the top mutational process. CONCLUSIONS: Elevated APE1 dysregulates homologous recombination and cell cycle, contributing to genomic instability, tumorigenesis, and chemoresistance, and its inhibitors have the potential to target these processes in EAC and possibly other cancers.

Efficacy of ozonated water over chlorhexidine mouth rinse in chronic gingivitis patients - A comparative clinical study.

Aim: This study aimed to compare the efficacy of ozonated water mouth rinse over chlorhexidine mouth rinse against the accumulation of plaque in chronic gingivitis patients. Materials and methods: A total of 30 patients with chronic generalized gingivitis were choosen for the study. The duration of this study was 15 days and was divided into three groups. Group 1 patients were advised to rinse with ozonated water¸ group 2 with a chlorhexidine mouth rinse and group 3 with water for 15 days. The clinical parameters like plaque index, gingival index, and bleeding index were recorded at baseline, 7th, and 15th day respectively. Saliva samples were collected for microbial culture at baseline that is before mouth rinse and on the 15th day that is after using mouth rinse from each patient. Results: The statistical analysis was performed by using ANOVA and Bonferroni's Post Hoc test on 30 patients at the end of the 15thday. There was a significant decrease in mean plaque, gingival, and bleeding scores in group 2 patients that are chlorhexidine mouth rinse. There was also a decrease in the microbial culture at the end of the 15th day in patients with chlorhexidine mouth rinse compared to ozonated water. Conclusion: The results of this study demonstrate that ozonated water was less effective compared to chlorhexidine mouth rinse in reducing plaque in gingivitis patients. But ozonated water can be used as an alternative to CHX.

Outcome of transcutaneous retrobulbar injection of liposomal amphotericin B in post-COVID-19 rhino-orbito-cerebral mucormycosis: Our experience.

Purpose: To assess the outcome and response of transcutaneous retrobulbar injection of amphotericin B (TRAMB) in post-coronavirus disease of 2019 (COVID-19) rhino-orbito-cerebral mucormycosis (ROCM) and to establish a scoring system in guiding treatment modalities. Methods: An interventional, prospective study was done on 82 eyes of post-COVID-19 ROCM from May 2021 to July 2021. A comprehensive multi-departmental evaluation along with detailed ophthalmic examination, laboratory investigations, and radiological examination was done. Scoring points were given to each symptom, sign, and radiological features of orbit and the total score was taken. Based on these scores, severity of disease was grouped into A, B, and C corresponding to mild, moderate, and severe orbital ROCM. One milliliter of reconstituted liposomal amphotericin B was given to all patients every alternate day as three doses. Efficacy of these injections was assessed in all groups, even though other treatment modalities like orbital debridement and exenteration were considered for moderate and severe cases. Patients were followed up for a period of 8 weeks. Results: Out of 82 eyes, symptomatic improvement was seen in a major proportion (72%) of patients. A statistically significant improvement in scores was noted in group A (93% improved) with a P value of 0.002, while 68.4% showed improvement in group B (P-value- 0.0001). Group C with severe disease showed minimal improvement in post-injection scores of 41% (P-value 0.086), necessitating surgical intervention. No serious adverse effect of the drug or procedure was noted. Conclusion: Significant improvement in scores of groups A and B highlights TRAMB as an effective and safe treatment modality in mild to moderate ROCM. It is an effective adjunct in severe cases, along with other interventions. Also, the scoring system helps in assessing the severity and guiding in management strategies.

Graphene Quantum Dot-Based Optical Sensing Platform for Aflatoxin B1 Detection via the Resonance Energy Transfer Phenomenon.

An optical sensing platform for the detection of an important mycotoxin, aflatoxin B1 (AFB1), in the absence of a bioactive environment is explored. In this work, a fluorescence-based sensing technique was designed by combining graphene quantum dots (GQDs) and AFB1 via fluorescence quenching, where AFB1 acts as the quencher of GQD fluorescence. GQDs were synthesized through a single-step hydrothermal reaction from the leaves of "curry tree" (Murraya Koenigii) at 200 °C. The fluorescent GQDs were quenched by AFB1 (quencher), which itself is detecting the analyte. Hence, this study reports the direct sensing of the mycotoxin AFB1 without the involvement of inhibitors or biological entities. The possible mode of quenching is the nonradiative resonance energy transfer between the GQDs and the AFB1 molecules. This innovative sensor could detect AFB1 in the range from 5 to 800 ng mL-1 with a detection limit of 0.158 ng mL-1. The interferent study was also carried out in the presence of different mycotoxins and carbohydrates (d-fructose, cellulose, and starch), which demonstrated the high selectivity and robustness of the sensor in the complex sample matrix. The recovery percentage of the spiked samples was also calculated to be up to 106.8%. Thus, this study reports the first GQD based optical sensor for AFB1.

Dysregulated APOBEC3G causes DNA damage and promotes genomic instability in multiple myeloma.

Multiple myeloma (MM) is a heterogeneous disease characterized by significant genomic instability. Recently, a causal role for the AID/APOBEC deaminases in inducing somatic mutations in myeloma has been reported. We have identified APOBEC/AID as a prominent mutational signature at diagnosis with further increase at relapse in MM. In this study, we identified upregulation of several members of APOBEC3 family (A3A, A3B, A3C, and A3G) with A3G, as one of the most expressed APOBECs. We investigated the role of APOBEC3G in MM and observed that A3G expression and APOBEC deaminase activity is elevated in myeloma cell lines and patient samples. Loss-of and gain-of function studies demonstrated that APOBEC3G significantly contributes to increase in DNA damage (abasic sites and DNA breaks) in MM cells. Evaluation of the impact on genome stability, using SNP arrays and whole genome sequencing, indicated that elevated APOBEC3G contributes to ongoing acquisition of both the copy number and mutational changes in MM cells over time. Elevated APOBEC3G also contributed to increased homologous recombination activity, a mechanism that can utilize increased DNA breaks to mediate genomic rearrangements in cancer cells. These data identify APOBEC3G as a novel gene impacting genomic evolution and underlying mechanisms in MM.

Salivaomics for Oral Cancer Detection: An Insight.

Early detection is very crucial for successful management of oral cancer or any disease as such. Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of malignancy of oral cavity. In the field of cancer research, there is always an ongoing quest for newer methods to lower the morbidity and mortality associated with OSCC. Saliva, a readily available noninvasive biofluid with constant contact with oral cancer lesion, offers an appealing alternative to serum and tissue testing. This review throws light on incorporation of newer technologies for harnessing the saliva to its fullest potential with increased specificity and sensitivity toward identification of cancer-specific molecular signatures for the development of point-of-care applications that could be used at the clinical setting.

Bioleaching of copper and nickel from mobile phone printed circuit board using Aspergillus fumigatus A2DS.

The recovery of metals from electronic waste was investigated by using fungal strain Aspergillus fumigatus A2DS, isolated from the mining industry wastewater. Fifty-seven percent of copper and 32% of nickel were leached (analyzed by Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-OES)) by the organism after one-step leaching at a temperature of 30 °C (shaking condition for 7 days). Maximum % of copper and nickel were obtained at a pH of 6 (58.7% Cu and 32% Ni), the temperature of 40 °C (61.8% Cu and 27.07% Ni), a pulp density of 0.5% (62% Cu and 42.37% Ni), and inoculums of 1% (58% Cu and 32.29% Ni). The XRD pattern of PCB showed 77.6% of copper containing compounds. XRD analysis of the leachate residue showed only 23.2% Euchorite (ASCu2H7O8) and 9.4% other copper containing compounds, indicating the leaching property of the fungus. HPLC analysis of the spent medium showed the presence of different acids like citric, succinic, and fumaric acid. The FTIR spectrum showed a decrease in carboxylic stretching in the leachate produced after bioleaching using spent medium. ICPOES of the leachate obtained using spent medium showed that 61% of the copper and 35% of nickel were leached out after seven days of incubation at shaking condition and 57% of copper and 32.8% of nickel at static condition confirming acidolysis property of the strain. A. fumigatus A2DS metal absorption and adsorption ability were observed using transmission electron microscopy (TEM) and scanning electron microscopy energy dispersive X-ray (SEM-EDX) respectively. The results thus indicate that bioleaching of Cu and Ni is bioleached by A. fumigatus A2DS.

Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids.

The exocrine pancreas, consisting of ducts and acini, is the site of origin of pancreatitis and pancreatic ductal adenocarcinoma (PDAC). Our understanding of the genesis and progression of human pancreatic diseases, including PDAC, is limited because of challenges in maintaining human acinar and ductal cells in culture. Here we report induction of human pluripotent stem cells toward pancreatic ductal and acinar organoids that recapitulate properties of the neonatal exocrine pancreas. Expression of the PDAC-associated oncogene GNASR201C induces cystic growth more effectively in ductal than acinar organoids, whereas KRASG12D is more effective in modeling cancer in vivo when expressed in acinar compared with ductal organoids. KRASG12D, but not GNASR201C, induces acinar-to-ductal metaplasia-like changes in culture and in vivo. We develop a renewable source of ductal and acinar organoids for modeling exocrine development and diseases and demonstrate lineage tropism and plasticity for oncogene action in the human pancreas.

Neuro-ophthalmic presentation of COVID-19 disease: A case report.

COVID-19 is a respiratory virus, which has affected various organ systems as well. Here we report a neuro-ophthalmic presentation of pituitary apoplexy under the setting of COVID-19 infection in a middle-aged man who presented to ophthalmic emergency with sudden bilateral loss of vision along with a history of fever past 10 days. There was sluggishly reacting pupils and RT-PCR for COVID was positive. Imaging pointed the diagnosis as pituitary macroadenoma with apopexy. In view of pandemic situation, patient was given symptomatic treatment as per the protocols and stabilized. Vision also showed improvement to some extent and the patient is awaiting neurosurgery.

Atranorin, an antimicrobial metabolite from lichen Parmotrema rampoddense exhibited in vitro anti-breast cancer activity through interaction with Akt activity.

Atranorin (ATR), lichenized secondary metabolite and depside molecule with several biological potentials such as antimicrobial, anticancer, anti-inflammatory, antinociceptive, wound healing and photoprotective activities. Cytotoxic reports of ATR are documented in several cancer cells and in vivo models but its molecular interaction studies are poorly understood. Therefore, in this present investigation, we have used the in silico studies with biological validation of the molecular targets for the anti-breast cancer mechanism of ATR. The molecular docking studies with the breast cancer oncoproteins such as Bcl-2, Bax, Akt, Bcl-w and Bcl-xL revealed the highest interaction was observed with the Akt followed by Bax, Bcl-xL and Bcl-2 & least with the Bcl-w proteins. The cytotoxicity studies showed ATR selectively inhibited MDA MB-231 and MCF-7 breast cancer cells in differential and dose-dependent manner with the IC50 concentration of 5.36 ± 0.85 µM and 7.55 ± 1.2 µM respectively. Further mechanistic investigations revealed that ATR significantly inhibited ROS production and significantly down-regulated the anti apoptotic Akt than Bcl-2, Bcl-xL and Bcl-w proteins with a significant increase in the Bax level and caspases-3 activity in the breast cancer cells when comparison with Akt inhibitor, ipatasertib. In vitro biological activities well correlated with the molecular interaction data suggesting that atranorin had higher interaction with Akt than Bax and Bcl-2 but weak interaction with Bcl-w and Bcl-xL. In this present study, the first time we report the interactions of atranorin with molecular targets for anti-breast cancer potential. Hence, ATR represents the nature-inspired molecule for pharmacophore moiety for design in targeted therapy.Communicated by Ramaswamy H. Sarma.

Water Drinking Practices in ADPKD Patients: A Questionnaire Based Study.

INTRODUCTION: Patients with autosomal dominant polycystic kidney disease (ADPKD) who have normal renal function (creatinine clearance, >90 ml per minute per 1.73 m2 of body-surface area) might potentially benefit from frequent water intake that would be sufficient to reduce plasma AVP levels and decrease the average urine osmolality, bringing it closer to that of plasma. MATERIALS AND METHODS: In this cross-sectional study, the patients of ADPKD, chronic kidney disease stages 1-5 were included. We formed a questionnaire on the dietary recommendation to the patients. The questions enquired whether the patients received the recommendation from the faculty and the postgraduates of the nephrology department that (a) they should consume at least 3000 mL of water per day, (b) that they should not consume coffee and tea,(c) adherence of patients to the advice of the nephrologists. RESULTS: Of 294 patients, 142 (48.2%) did not receive any dietary recommendation. The rest 152 (51.7%) were given the appropriate dietary recommendation. Majority of the patients mentioned that they lacked the access to the water when they intend to consume. Despite the advice from the nephrologists, 95 (32.3%) failed to observe the abstinence from coffee and tea. The reason expressed for not quitting coffee and tea was the force of the habit. CONCLUSION: Treating doctorsfailed to inform 48% of patients the proper diet. Only 20.3% of patients consumed >3.0 litre of water per day. The demand of the agricultural work at a place away from home deprived majority of the participants of the study from the potable water.