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Histological interpretation of the rare pleomorphic xanthoastrocytoma (PXA) has been the holy grail for treatment options. However, no stand-alone clinical interventions have been developed owing to the lack of gene expression profiling data in PXA/APXA patients. We first time report the comprehensive analyses of the coding as well as long non-coding RNA (lncRNA) signatures of PXA/APXA patients. Several genes such as IGFBP2, NF1, FOS, ERBB2, and lncRNAs such as NEAT1, HOTAIRM1, and GAS5 known to play crucial roles in glioma patients were also deregulated in PXA patients suggesting the commonality in the molecular signatures. PPI network, co-expression, and lncRNA-mRNA interaction studies unraveled hub genes (such as ERBB2, FOS, RPA1) and networks that may play a critical role in PXA biology. The most enriched pathways based on gene profiles were related to TLR, chemokine, MAPK, Rb, and PI3K-Akt signaling pathways. The lncRNA targets were enriched in glucuronidation, adipogenesis, TGF-beta signaling, EGF/EGFR signaling, and cell cycle pathways. Interestingly, several mRNAs like PARVG, and ABI2 were found to be targeted by multiple lncRNAs suggesting a tight control of their levels. Some of the most prominent lncRNA-mRNA pairs were LOC728730: MRPL9, XLOC_l2_011987: ASIC2, lnc-C1QTNF5-1: RNF26. Notably, several lncRNAs such as lnc-CETP-1, lnc-XRCC3-1, lnc-RPL31-1, lnc-USP13-1, and MAPKAPK5-AS1, and genes such as RPA1, NTRK3, and CNRP1 showed strong correlation to the progression-free survival of PXA patients suggesting their potential as novel biomarkers. Overall, the findings of this study may facilitate the development of a new realm of RNA biology in PXA that may have clinical significance in the future.

Background Stenotrophomonas maltophilia causes opportunistic infections in immunocompromised and patients in intensive care units (ICUs). An outbreak of S. maltophilia in ICU is described which highlights the importance of the risk of infection from contaminated medical devices and suction fluids in ventilated patients. Methods The investigation of the outbreak was carried out. Environmental sampling was done. This was followed by MALDI-TOF MS typing and recA gene-based-phylogeny. Results In February, S. maltophilia was reported from the central line blood of six patients from ICU within a span of two weeks. The peripheral line blood cultures were sterile in all patients. Relevant environmental sampling of the high-touch surface and fluids revealed S. maltophilia strains in normal saline used for suction and in the inspiratory circuit of two patients. The isolated strains from patients and environment (inspiratory fluid) showed a minimum of 95.41% recA gene sequence identity between each other. Strict cleaning and disinfection procedures were followed. Continuous surveillance was done and no further case of S. maltophilia was detected. Timely diagnosis and removal of central line prevented development of central-line associated blood stream infection. Conclusion This outbreak report illustrates that environmental sources like suction fluid and normal saline could be the source of S. maltophilia in ICU patients.

Accurately predicting red blood cell (RBC) transfusion requirements in cardiothoracic (CT) surgery could improve blood inventory management and be used as a surrogate marker for assessing hemorrhage risk preoperatively. We developed a machine learning (ML) method to predict intraoperative RBC transfusions in CT surgery. A detailed database containing time-stamped clinical variables for all CT surgeries from 5/2014–6/2019 at a single center (n = 2410) was used for model development. After random forest feature selection, surviving features were inputs for ML algorithms using five-fold cross-validation. The dataset was updated with 437 additional cases from 8/2019–8/2020 for validation. We developed and validated a hybrid ML method given the skewed nature of the dataset. Our Gaussian Process (GP) regression ML algorithm accurately predicted RBC transfusion amounts of 0 and 1–3 units (root mean square error, RMSE 0.117 and 1.705, respectively) and our GP classification ML algorithm accurately predicted 4 + RBC units transfused (area under the curve, AUC = 0.826). The final prediction is the regression result if classification predicted

Nanotechnology and material science developments emerge in the manufacturing of various novel modes of drug delivery, which have proven scientifically promising. Polymer nanoparticles have high stability, high specificity, high drug-carrying power, control release, and potential to be used in various pathways. They usually supply hydrophilic and hydrophobic molecules with medicines. In this review, we have discussed the different types of brain tumour, different PLGA (Poly Lactic-co-Glycolic Acid) nanostructures, PLGA in brain tumour targeting, and the recent advancement of PLGA based nanoparticles. This review focused on the method of preparation of polymeric nanoparticles, the significance of EPR (Enhanced Permeability and Retention) effect with PLGA, the significance of TPGS in cancer, and discussed the pharmaceutical application of PLGA nanoparticles. We expect these polymeric nanoparticles will be very successful and efficient for disease targeting in the future and new techniques will emerge.

Cancer is one of the most prevailing disease conditions, which occurs due to uncontrolled cell division either due to natural mutation to the genes or due to changes induced by physical, chemical, or biological carcinogens. According to WHO, it is the second leading cause of death worldwide and has reported 10 million deaths in 2020. Hence, there arises the need for better chemotherapies and DNA intercalators are one such emerging therapy for cancer. DNA intercalating agents reversibly intercalate with the double-helical structure of DNA by interacting with adjacent base pairs and disrupting the structure of DNA and thereby causing cell death. Here, we discuss the different classes of organo-intercalators used in cancer therapy describing their anticancer and intercalation ability by different methods along with their structure-activity relationship and mechanism of action.

OBJECTIVE The aim of this study was to compare the performance of angiogenesis-specific 68Ga-RGD2 PET/CT with Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) in assessing disease activity and treatment response in rheumatoid arthritis (RA). METHODS This was a prospective study comparing the performance of 68Ga-RGD2 PET/CT and DAS28-ESR in 30 RA patients. All of them underwent 68Ga-RGD2 PET/CT scan from head to toe and clinical examination at the baseline. A repeat scan and clinical examination were done in 27 patients after 3 months of treatment with disease-modifying antirheumatic drugs ± steroids. Three PET parameters, that is, PJC (PET-positive joint count), aSUVmax (average SUVmax), and hSUVmax (highest SUVmax), of positive joints were compared with the DAS28-ESR for disease activity assessment and response evaluation. RESULTS Among the 3 PET parameters, PJC showed a significant correlation with the DAS28-ESR (0.64, P < 0.01). A significant change was observed with treatment in the DAS28-ESR and PET parameters of 27 patients at follow-up. There was significant correlation between percentage changes in DAS28-ESR and scan parameters such as PJC (0.689, P < 0.001), aSUVmax (0.712, P < 0.001), and hSUVmax (0.555, P = 0.003) values. The absolute change in aSUVmax value could accurately discriminate (area under the curve, 0.98; P = 0.001) European League Against Rheumatism responders from nonresponders. CONCLUSIONS 68Ga-RGD2 PET/CT is a promising tool for objective assessment of disease activity and treatment response in patients with RA.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in humans. Hypoxia has been correlated with the aggressive form of glial tumors, poor prognosis, recurrence and resistance to various therapies. MicroRNAs (miRNAs) have emerged as critical mediators of hypoxic responses and have shown great potential for cancer diagnostics and therapeutics. Here, we focus on the regulatory and functional characterization of miR-196a, a hypoxia-inducible miRNA, in GBM. Hypoxia/HIF regulation of miR-196a was assessed by RT-qPCR, promoter-luciferase and ChIP assays in GBM cell lines. miR-196a levels were analyzed in The Cancer Genome Atlas (TCGA)-GBM, Chinese Glioma Genome Atlas (CGGA) and Indian GBM patient cohorts. miR-target interactions were studied using RNA/protein quantification and 3’UTR luciferase assays. The effect of miR-196a overexpression/inhibition was assessed on cellular viability, migration and apoptosis under hypoxia and normoxia. Microarray-based gene expression profiling studies were performrd to study the effect of miR-196a on the GBM cellular transcriptome under hypoxia. We identified miR-196a as a hypoxia-inducible and hypoxia-inducible factor (HIF)-regulated miRNA that plays an oncogenic role in GBM. miR-196a was found to be significantly up-regulated in TCGA-GBM, CGGA glioma as well as Indian GBM patient cohorts. miR-196a overexpression was found to induce cellular proliferation, migration, spheroid formation and colony formation and to inhibit apoptosis, while miR-196a inhibition using anti-miR-196a yielded opposite results, suggesting an oncogenic role of miR-196a in GBM. We further unveiled NRAS, AJAP1, TAOK1 and COL24A1 as direct targets of miR-196a. We also report a complex competitive regulation of oncogenic NRAS by miR-196a, miR-146a and let-7 in GBM. Analysis of microarray-based gene expression data obtained by miR-196a inhibition under hypoxia revealed a role of miR-196a in HIF, calcium adhesion, Wnt and cell adhesion pathways. Interestingly, miR-196a was found to positively regulate the expression of various genes involved in the induction or stabilization of HIFs and in maintenance of hypoxic conditions, thereby suggesting the existence of an indirect miR-196a/HIF positive feedback loop under hypoxia. Overall, our work identifies a novel association between hypoxia/HIF signalling and miR-196a in GBM and suggests its therapeutic significance.

Objective:The aim of this study was to identify factors associated with acceptability and efficacy of yoga training (YT) for improving cognitive dysfunction in individuals with schizophrenia (SZ).Methods:We analysed data from two published clinical trials of YT for cognitive dysfunction among Indians with SZ: (1) a 21-day randomised controlled trial (RCT, N = 286), 3 and 6 months follow-up and (2) a 21-day open trial (n = 62). Multivariate analyses were conducted to examine the association of baseline characteristics (age, sex, socio-economic status, educational status, duration, and severity of illness) with improvement in cognition (i.e. attention and face memory) following YT. Factors associated with acceptability were identified by comparing baseline demographic variables between screened and enrolled participants as well as completers versus non-completers.Results:Enrolled participants were younger than screened persons who declined participation (t = 2.952, p = 0.003). No other characteristics were associated with study enrollment or completion. Regarding efficacy, schooling duration was nominally associated with greater and sustained cognitive improvement on a measure of facial memory. No other baseline characteristics were associated with efficacy of YT in the open trial, the RCT, or the combined samples (n = 148).Conclusions:YT is acceptable even among younger individuals with SZ. It also enhances specific cognitive functions, regardless of individual differences in selected psychosocial characteristics. Thus, yoga could be incorporated as adjunctive therapy for patients with SZ. Importantly, our results suggest cognitive dysfunction is remediable in persons with SZ across the age spectrum.

Paclitaxel-induced photodermatitis is extremely rare despite the frequent use of paclitaxel-trastuzumab combination chemotherapy. A 70-year-old woman with infiltrating intraductal breast cancer developed photodermatitis after ten treatment courses of weekly paclitaxel-trastuzumab combination chemotherapy. Withdrawal of paclitaxel and sun avoidance led to its resolution. A combined effect of solar radiation and enhanced porphyrin synthesis is speculated for photodermatitis in paclitaxel. However, the issue of aberrant porphyrin biosynthesis being causal or an epiphenomenon remains unsettled as elevated porphyrins synthesis does not necessarily cause photosensitivity in all treated cases. The relevant literature on paclitaxel-induced photodermatitis and pathomechanism involved is reviewed.

Idiopathic intracranial hypertension (IIH) is well-described entity in literature. However, large studies on clinical and radiological profile are still very few from the Indian subcontinent.To analyze the clinical and radiological profile of IIH and correlation of various clinical and radiological parameters with papilledema and CSF opening pressure.Hospital-based observational, descriptive study.This study analyzed 122 patients admitted in the department of Neurology (from January 2014 to December 2018) for detailed history, clinical examination, and neuroimaging. CSF manometry and routine CSF analysis were done. All participants met the modified Dandy criteria. Patients with secondary causes of raised ICP and primary ocular pathology were excluded.Descriptive statistics and Chi-square test.Among 122 cases 86 (70.49%) were females. The mean age was 33 years. 62 (50.82%) cases were obese. Headache was the most common symptom (114/122; 93.44%). Bilateral papilledema was noted in 114 (93.44%) cases. Higher grades of papilledema had a correlation with higher CSF opening pressure. Empty sella was the most common radiological finding (100/122; 81.97%). All radiological findings except empty sella had a correlation with higher CSF opening pressure.IIH typically affects obese females of childbearing age group. However, it is not uncommon in the nonobese and male sex. Obesity may not be a dominant risk factor for the development of IIH in the Indian subcontinent. Cases with normal BMI and male sex with clinical features of raised intracranial pressure and normal neuroimaging should also be evaluated for IIH. Cases with refractory headache and empty sella on MRI should be evaluated for IIH.

Postoperative atrial fibrillation (POAF) after cardiac surgery remains a highly prevalent and costly condition that negatively impacts patient quality of life and survival. Numerous retrospective studies, meta-analysis, and review papers have been reported identifying POAF risk based on patients' risk factors and clinical biomarkers. In this narrative review, the authors report significant variations among selected pre- and perioperative biomarkers used to predict POAF incidence in patients without a history of atrial fibrillation (AF). POAF prediction based on B-type natriuretic peptide, N-terminal pro B-type natriuretic peptide, C-reactive protein, interleukin-6, creatinine, and plasminogen activator inhibitor-1 differs significantly among different studies, thereby limiting their clinical utility to predict POAF risk with high accuracy. Conversely, soluble vascular endothelial cells adhesion molecule-1, soluble CD40 ligand, Galectin-3, and aldosterone show promise for better POAF prediction. However, the current datasets for these selected biomarkers are not of sufficient size to validate the broad clinical application specifically for patients with no prior history of AF.

To evaluate and analyze the outcomes of sutureless and glue-free limbal-conjunctival autografting in cases of primary as well as recurrent pterygium.This prospective interventional study was carried out between February 2019 and February 2020 at a tertiary care hospital in North India. A.total of 70 patients with pterygium underwent sutureless and glue-free limbal-conjunctival autograft. The patients were divided into two groups: group 1 patients with primary pterygium (n = 45), group 2 patients with recurrent pterygium (n = 25). The patients were followed up till 12 months postoperatively.The mean age of the patients in group 1 and group 2 was 37.04 ± 8.69 years and 32.52 ± 6.49 years, respectively (P = 0.04). Postoperatively, no recurrence was recorded in group 1. Recurrence was noticed in two patients (8%) of group 2. The BCVA changed from 78.73 ± 9.86 letters to 80.15 ± 7.29 letters (P = 0.45) and from 79.6 ± 6.44 letters to 79.8 ± 5.86 letters (P = 0.45) in group 1 and group 2, respectively. Graft edema was found in seven (15.55%) cases of group 1 and four (16%) cases of group 2. Graft retraction was found in two (4.44%) cases of group 1 and three (12%) cases of group 2.Sutureless and a glue-free limbal-conjunctival autograft is a safe and effective treatment option for primary as well as recurrent pterygium.

The current study was conducted to examine the in vitro anticancer potential of

Glioblastoma is the most life-threatening tumor of the central nervous system. Despite recent therapeutic advancements, maximum survival of glioblastoma patients remains dismal. The mediator complex is a set of proteins, essential for eukaryotic gene expression. Abnormal expression/mutations of specific mediator genes have been associated with progression of various cancers, however, its role and status in glioblastoma remains largely unknown. Our work shows overexpression of a subunit of kinase assembly of mediator complex, MED12, in various glioblastoma patient cohorts including Indian glioblastoma patients and cell lines. Functional characterization of MED12 using both overexpression and knockdown approach revealed that it promotes glioblastoma cell proliferation, migration and inhibits apoptosis. Transcriptome analysis post MED12 knockdown revealed Vitamin D receptor (VDR) pathway to be one of the key pathways affected by MED12 in glioblastoma. We studied direct interaction of MED12 with VDR protein using docking studies and co-immunoprecipitation assay. We identify BCL6, a secondary regulator of VDR signaling, to be directly regulated by MED12 through a combination of chromatin immunoprecipitation, qRT-PCR and western analyses. We further show that MED12 brings about the inhibition of p53 levels and apoptosis partly through induction of BCL6 in glioblastoma. Overall, this stands as the first report of MED12 over-expression and involvement in glioblastoma pathogenesis and identifies MED12 as an important mediator of VDR signaling and an attractive molecule for development of new therapeutic interventions.

Rheumatoid arthritis (RA) can have various infectious mimics. As immunosuppressive agents used in treatment can aggravate the underlying infections, correct diagnosis of RA and ruling out infections is important. Numerous viral infections (Parvovirus B19, Hepatitis B, Hepatitis C, Chikungunya and other alphaviruses, human immunodeficiency virus (HIV) and various other viruses), mycobacterial infections (Poncet's disease, tubercular septic arthritis, and leprosy), bacterial arthritis, brucellosis and Lyme disease are among common infections that mimic RA. Widespread travel and tourism, especially to exotic areas, high risk sexual behavior and widespread use of immunosuppressive and chemotherapeutic agents has led to numerous outbreaks of infections in areas where these infections were never reported before. Hence, rheumatologists all over the world should be familiar with musculoskeletal manifestations of infections. History of travel, comorbid fever, skin rash, genital ulcers, urethral discharge, the consumption of unpasteurized milk, lymphadenopathy, tenosynovitis, low platelet count, and positive Mantoux test can offer potential diagnostic clues. Serological testing, cultures, specific radiological signs and deoxyribonucleic Acid (DNA) amplification techniques often aid in diagnosis. Treatment mainly consists of antimicrobial agents, analgesics, and nonsteroidal anti-inflammatory drugs (NSAIDs). However, immunosuppressive agents including steroids and disease modifying anti-rheumatic drugs (DMARDs) are needed occasionally in different refractory and prolonged illnesses. Most of the times, episodes of arthritis are self-limiting and respond to treatment of underlying cause. However, few infections like Chikungunya and Lyme's disease can lead to chronic arthritis as well.

Intraventricular tumors pose a surgical challenge because of the difficulty in reaching their deep location through safe corridors and their adherence or proximity to vital neurovascular structures. Although microneurosurgery is the mainstay of surgical management, neuroendoscopy aided by adjuncts, namely, navigation and ultrasonic aspirators, has made a great contribution to improving surgical results.This article reviews the experience of a neurosurgical unit with endoscopic procedures for intraventricular tumors. The current indications, benefits, and complications of neuroendoscopy are described.This is a retrospective, observational study of lateral and third ventricular tumors tackled either purely with an endoscope or with its assistance over 19 years in a single unit at Bombay Hospital Institute of Medical Sciences, Mumbai.Of a total of 247 operated patients with intraventricular tumors, 85 cases operated using an endoscope were included. The majority of the patients had a tumor in the third ventricle (n = 62), whereas 23 patients had tumor in the lateral ventricle. The most common pathologies were colloid cyst and arachnoid cyst (n = 18). An endoscope was used for microsurgical assisted excision of tumors in 31 cases, biopsy in 24, cyst fenestration in 23, and pure endoscopic excision in seven cases.Microsurgery remains the gold standard for the removal of giant, vascular intraventricular tumors. However, endoscopic fenestration or excision of cysts and biopsy have become better alternatives in many cases. Endoscope-assisted microsurgery affords safety and helps in achieving a more complete excision.

Background Coronary artery bypass can be performed off pump (OPCAB) without cardiopulmonary bypass. However, trends over time for OPCAB versus on‐pump (ONCAB) use and long‐term outcome has not been reported, nor has their long‐term outcome been compared. Methods and Results We queried the national Veterans Affairs database (2005–2019) to identify isolated coronary artery bypass procedures. Procedures were classified as OPCAB on ONCAB using the as‐treated basis. Trend analyses were performed to evaluate longitudinal changes in the preference for OPCAB. The median follow‐up period was 6.6 (3.5–10) years. An inverse probability weighted Cox model was used to compare all‐cause mortality between OPCAB and ONCAB. From 47 685 patients, 6759 (age 64±8 years) received OPCAB (14%). OPCAB usage declined from 16% (2005–2009) to 8% (2015–2019). Patients with triple vessel disease who received OPCAB received a lower mean number of grafts (2.8±0.8 versus 3.2±0.8; P The ONCAB 5‐, 10‐, and 15‐year survival rates were 82.9% (82.5–83.3), 60.4% (59.8–61.1), and 37.2% (36.1–38.4); correspondingly, OPCAB rates were 80.7% (79.7–81.7), 57.4% (56–58.7), and 34.1% (31.7–36.6) ( P P P Conclusions Over 15 years, OPCAB use declined considerably in Veterans Affairs medical centers. In Veterans Affairs hospitals, late all‐cause mortality and myocardial infarction rates were higher in the OPCAB cohort.

Abnormal emotional processing in major depressive disorder (MDD) has been associated with increased activation to negative stimuli in cortico-limbic brain regions. The authors investigated whether treatment with BI 1358894, a small-molecule inhibitor of the transient receptor potential cation channel subfamily C leads to attenuated activity in these areas in MDD patients. 73 MDD patients were randomized to receive a single oral dose of BI 1358894 (100 mg), citalopram (20 mg), or matching placebo. Brain responses to emotional faces and scenes were investigated using functional magnetic resonance imaging. Primary endpoints were BOLD signal changes in response to negative faces in cortico-limbic brain regions, i.e. bilateral amygdala (AMY), dorsolateral prefrontal cortex, anterior insula (AI), and anterior cingulate cortex. Secondary endpoints were BOLD signal changes in response to negative scenes. For each region, separate ANOVA models were computed for the comparison of treatments (BI 1358894 or citalopram) vs. placebo. The adjusted treatment differences in the % BOLD signal changes in the faces task showed that BI 1358894 induced signal reduction in bilateral AMY and left AI. In the scenes task, BI 1358894 demonstrated significant signal reduction in bilateral AMY, AI, anterior cingulate cortex and left dorsolateral prefrontal cortex. Citalopram failed to induce any significant reductions in BOLD signal in both tasks. BI 1358894-mediated inhibition of the transient receptor potential cation channel subfamily resulted in strong signal reduction in cortico-limbic brain regions, thereby supporting development of this mechanism of action for MDD patients.

We have previously reported that hexamethylene bis-acetamide inducible protein 1 (HEXIM1) inhibits the activity of ligand-bound estrogen receptor α (ERα) and the androgen receptor (AR) by disrupting the interaction between these receptors and positive transcriptional elongation factor b (P-TEFb) and attenuating RNA polymerase II (RNAPII) phosphorylation at serine 2. Functional consequences of the inhibition of transcriptional activity of ERα and AR by HEXIM1 include the inhibition of ERα- and AR-dependent gene expression, respectively, and the resulting attenuation of breast cancer (BCa) and prostate cancer (PCa) cell proliferation and growth. In our present study, we determined that HEXIM1 inhibited AKR1C3 expression in BCa and PCa cells. AKR1C3, also known as 17β-hydroxysteroid dehydrogenase (17β-HSD) type 5, is a key enzyme involved in the synthesis of 17β-estradiol (E2) and 5-dihydrotestosterone (DHT). Downregulation of AKR1C3 by HEXIM1 influenced E2 and DHT production, estrogen- and androgen-dependent gene expression, and cell proliferation. Our studies indicate that HEXIM1 has the unique ability to inhibit both the transcriptional activity of the ER and AR and the synthesis of the endogenous ligands of these receptors.

The increasing agro-demands with the burgeoning population lead to the accumulation of lignocellulosic residues. The practice of burning agri-residues has consequences viz. Release of soot and smoke, nutrient depletion, loss of soil microbial diversity, air pollution and hazardous effects on human health. The utilization of agricultural waste as biomass to synthesize biochar and biofuels, is the pertinent approach for attaining sustainable development goals. Biochar contributes in the improvement of soil properties, carbon sequestration, reducing greenhouse gases (GHG) emission, removal of organic and heavy metal pollutants, production of biofuels, synthesis of useful chemicals and building cementitious materials. The biochar characteristics including surface area, porosity and functional groups vary with the type of biomass consumed in pyrolysis and the control of parameters during the process. The major adsorption mechanisms of biochar involve physical-adsorption, ion-exchange interactions, electrostatic attraction, surface complexation and precipitation. The recent trend of engineered biochar can enhance its surface properties, pH buffering capacity and presence of desired functional groups. This review focuses on the contribution of biochar in attaining sustainable development goals. Hence, it provides a thorough understanding of biochar's importance in enhancing soil productivity, bioremediation of environmental pollutants, carbon negative concretes, mitigation of climate change and generation of bioenergy that amplifies circular bioeconomy, and concomitantly facilitates the fulfilment of the United Nation Sustainable Development Goals. The application of biochar as seen is primarily targeting four important SDGs including clean water and sanitation (SGD6), affordable and clean energy (SDG7), responsible consumption and production (SDG12) and climate action (SDG13).

Metastatic prostate cancer (mCaP) remains one of the leading causes of cancer-related death in men worldwide. Androgen receptor (AR) drives the progression of most of the mCaP, and hence the androgen deprivation therapy (ADT) is the first-line treatment of choice for mCaP. Although the responses of ADT and next-generation AR inhibitors initially improve the disease burden, the responses of this combinatorial drug therapy varied widely due to molecular alteration in mCaP patients. In addition to the altered AR signaling, loss of potent tumor-suppressor protein p53 exhibits poor outcomes. p53 influences cell plasticity and is frequently lost in more aggressive prostate cancer (CaP) with neuroendocrine differentiation. Loss of p53 antagonizes the effect of AR inhibitors and enhances the proliferation rate of CaP cells. Considering the important role of p53 inactivation in cancer development, restoration of wild-type p53 function by p53-reactivating compounds developed with different approaches, seems to be an attractive therapeutic strategy for prostate cancer therapy. In this review, we discuss the therapeutic potential of these compounds with a particular focus on the pharmacological rescue of p53 in mCaP. In addition, we also highlight the challenges and new opportunities of p53-targeted therapy for the future.

Twenty novel 1,2,3-triazole benzenesulfonamides featuring nitrile 8a-g, carbothioamide 9a-f, and N'-hydroxycarboximidamide 10a-g functionalities were designed and synthesized to improve potency and selectivity as carbonic anhydrase inhibitors (CAIs). The synthesized 1,2,3-triazole compounds were tested in vitro as CAIs against four physiologically and pharmacologically relevant isoforms of human carbonic anhydrase (hCA I, II, IV, and IX). Compounds 8a-g, 9a-f, and 10a-g displayed variable inhibition constants ranging from 8.1 nM to 3.22 μM for hCA I, 4.7 nM to 0.50 μM for hCA II, 15.0 nM to 3.7 μM for hCA IV, and 29.6 nM to 0.27 μM for hCA IX. As per the inhibition data profile, compounds 9a-e exhibited strong efficacy for hCA IV, whereas the inhibition was found to be somewhat diminished in the case of hCA IX by nearly all the compounds. A computational protocol based on docking and MM-GBSA was conducted to reveal the plausible interactions of the targeted sulfonamides within the hCA II and IX binding sites. The outcomes of appending various functionalities at the C-4 position of the 1,2,3-triazole motif over the inhibition potential and selectivity of the designed sulfonamides were examined with a potential for the discovery of new isoform selective CAIs. The CAI and SAR data established the significance of the synthesized 1,2,3-triazoles as building blocks for developing CAI drugs.

Objective To evaluate 18F-fluorodeoxyglucose (FDG) PET/CT in the assessment of disease activity, extent of the disease and response to therapy in relapsing polychondritis. Methods Twenty-five patients (9 men, 16 women) with a mean age of 38.2 years (s.d. 13.7; range 18–62), diagnosed to have relapsing polychondritis according to Damiani and Levine’s modification of McAdam’s criteria, who underwent PET/CT examination were included. Ten patients underwent a second PET/CT examination after therapy or during follow-up. Clinical symptoms and auxiliary examination findings were recorded. PET/CT findings were reviewed and correlated with the clinical symptoms. Results The major symptoms were aural pain (n = 21), nasal pain (n = 10), stridor (n = 5), cough (n = 9), fever (n = 8) and laryngeal tenderness (n = 8). The initial PET/CT was positive in 23/25 patients. PET/CT revealed involvement of auricular (n = 14), nasal (n = 8), laryngeal (n = 7), tracheobronchial (n = 6) and Eustachian (n = 3) cartilages with a mean maximum standardized uptake value (SUVmax) of 4.1 (s.d. 2.5; range 1.7–12.7). Fair correlation of aural/nasal pain/stridor with FDG avidity of cartilage involvement on PET/CT was noted. The key finding was detection of asymptomatic large airway involvement in seven patients (28%). Re-examination PET in 10 patients revealed complete therapeutic response (n = 5), partial response (n = 1), stable disease (n = 1), progressive disease (n = 1) and disease recurrence (n = 2). Conclusion FDG PET/CT is a useful tool for the assessment of the disease activity and extent. It identified activity in clinically inaccessible sites that are of clinical significance. It is also useful in assessing treatment response and finding relapse.

Recent advancement in understanding cancer etiology has highlighted epigenetic deregulation as an important phenomenon leading to poor prognosis in glioblastoma (GBM). Polycomb repressive complex 2 (PRC2) is one such important epigenetic modifier reportedly altered in GBM. However, its defined mechanism in tumorigenesis still remains elusive. In present study, we analyzed our in-house ChIPseq data for H3k27me3 modified miRNAs and identified miR-490-3p to be the most common target in GBM with significantly downregulated expression in glioma patients in both TCGA and GBM patient cohort. Our functional analysis delineates for the first time, a central role of PRC2 catalytic unit EZH2 in directly regulating expression of this miRNA and its host gene CHRM2 in GBM. In accordance, cell line treatment with EZH2 siRNA and 5-azacytidine also confirmed its coregulation by CpG and histone methylation based epigenetic mechanisms. Furthermore, induced overexpression of miR-490-3p in GBM cell lines significantly inhibited key hallmarks including cellular proliferation, colony formation and spheroid formation, as well as epithelial-to-mesenchymal transition (EMT), with downregulation of multiple EMT transcription factors and promigratory genes (MMP9, CCL5, PIK3R1, ICAM1, ADAM17 and NOTCH1). We also for the first time report TGFBR1 and TGIF2 as two direct downstream effector targets of miR-490-3p that are also deregulated in GBM. TGIF2, a novel target, was shown to promote migration and EMT that could partially be rescued by miR-490-3p overexpression. Overall, this stands as a first study that provides a direct link between epigenetic modulator EZH2 and oncogenic TGF-β signaling involving novel miR-490-3p/TGIF2/TGFBR1 axis, that being targetable might be promising in developing new therapeutic intervention strategies for GBM.

Psoriasis is now recognized as an immune-mediated inflammatory dermatosis with increased risk for metabolic syndrome, its individual components, and cardiovascular disease. We quantitatively estimated malondialdehyde (MDA), lipoprotein-a (LP-a), lipoprotein ratios, comprehensive lipid tetrad index (CLTI), and atherogenic index (AI), and evaluated cardiovascular risk in 132 (M:F 94:38) patients with psoriasis aged 20–79 years with chronic plaque psoriasis and equal number of age and gender-matched controls. Lipoprotein ratios, CLTI and AI were calculated using standard formulae. Cardiovascular 10-year risk was graded by Framingham risk score (FRS) as low, intermediate and severe. Mild-to-moderate and severe psoriasis was present in 125 (94.7%), and 7 (5.3%) patients, respectively, and 19 (14.39%) patients had psoriatic arthritis. Statistically significant differences were noted for LDL, LDL/HDL, non-HDL/HDL, MDA, LP-a, AI and CLTI. There was a significantly positive correlation between PASI with LP-a (p = 0.003, r = 0.25) and AI (p = 0.012, r = 0.22). Serum levels of MDA correlated positively with LP-a (p

Nature has been a source of a wide range of products being utilized for the treatment of various diseases like malaria, cancer, diabetes etc. Among these, cancer is emerging as a leading cause of deaths worldwide and the development of cross-resistance to already established drugs increases the need for novel anticancer drugs. To discover novel anticancer molecules, it is a necessity to unearth the molecules which can act as anticancer agents. Taking natural products in vision, phytoconstituents like terpenoids, flavones, glycosides and alkaloids might act as a major source of lead molecules. Considering the anticancer prospectives of phytoconstituents, different unknown lead molecules are summarized in this review. The present review highlights the representative studies of plant-based anticancer agents which are classified as per their phytochemical nature. Furthermore, important key points along with important structure-activity relationships points regarding selected lead molecules are also discussed.

Background: This study evaluated the efficacy and safety of intralesional bleomycin in the treatment of common warts in 50 (32 men, 18 women) patients aged between 14 and 80 (mean ± SD, 28.5 ± 13.27) years. Methods: The warts were present over dorsal hands, feet, palms, soles and periungual skin for 1 month to 10 years. They were infiltrated with bleomycin (1 mg/ml) till blanching. The total cumulative dose did not exceed 2 mg in one session. The treatment was repeated after paring of eschar at 2 weeks in case there was no or partial response. The patients were reviewed at 4, 12 and 24 weeks for cure, adverse effects or recurrences and outcome satisfaction levels. Results: Complete cure without recurrence occurred in 40 (80%) patients and partial response occurred in 7 (14%) patients at the end of the 24-week study period. Three patients did not complete follow-up. No major systemic or local adverse effects other than injection site pain for 2–3 days were noted. All cured patients were very satisfied (Likert scale 5). Conclusion: Intralesional bleomycin appears to be an effective and safe treatment for common warts including palmoplantar and periungual warts. It carries the advantage of low dose, no significant adverse effects and high patient satisfaction. Small number of patients, lack of a control group, comparing different bleomycin concentrations and a short follow-up are a few limitations of this study. Better designed studies are warranted for this useful treatment modality.

Cancer is a kind of human cell degenerative disease that has affected many people for several years. Cancer is caused due to the abnormal growth of cells in every particular part of the body. The 1,3,4-oxadiazole ring is found to be a binding moiety that has anticancer potential. Various works on the 1,3,4-oxadiazole moiety showing anticancer activity have been reported. The present analysis summarizes general synthetic methods for 1,3,4 oxadiazole. Different receptors on which these drug acts are discussed. This review also presents pharmacophore models for topoisomerase-I, histone deacetylase, and epidermal growth factor enzymes.

BACKGROUNDpostoperative atrial fibrillation (POAF) is a common cardiac surgery complication that is associated with increased complications and negative outcomes, but the association between presurgical atrial conduction abnormalities and POAF has not been investigated clinically during premature atrial S1S2 stimulation. This clinical study sought to examine whether intraoperative premature atrial stimulation reveals increased areas of slowed and/or blocked conduction in patients that develop POAF.METHODSHigh-density intraoperative epicardial left atrial mapping was conducted in 20 cardiac surgery patients with no prior history of atrial fibrillation (AF). In 20 patients, 6 (30%) developed POAF. A flexible-array of 240-electrodes was placed on the posterior left atrial wall in between the pulmonary veins. Activation maps were generated for sinus and premature atrial S1S2 stimulated beats. The area of conduction block (CB), conduction delay (CD) and the combination of both (CDCB) for conduction velocity RESULTSFor a premature atrial S2 beat with shortest cycle length captured, conduction velocity maps revealed a significantly higher area for CD (13.19±6.59 versus 6.06±4.22 mm2, p=0.028) and CDCB (17.36±8.75 versus 7.41±6.39 mm2, p=0.034), and a trend toward a larger area for CB (4.17±3.66 versus 1.34±2.86 mm2, p=0.063) in patients who developed POAF in comparison to those that remained in the sinus. Sinus and S1 paced beats did not show substantial differences in abnormal conduction areas between patients with and without POAF.CONCLUSIONIn comparison to sinus and S1 beats, premature atrial S2 beats accentuate conduction abnormalities in cardiac surgery patients that developed POAF.

National and institutional quality initiatives provide benchmarks for evaluating the effectiveness of medical care. However, the dramatic growth in the number and type of medical and organizational quality-improvement standards creates a challenge to identify and understand those that most accurately determine quality in cardiac surgery. It is important that surgeons have knowledge and insight into valid, useful indicators for comparison and improvement. We therefore reviewed the medical literature and have identified improvement initiatives focused on cardiac surgery. We discuss the benefits and drawbacks of existing methodologies, such as comprehensive regional and national databases that aid self-evaluation and feedback, volume-based standards as structural indicators, process measurements arising from evidence-based research, and risk-adjusted outcomes. In addition, we discuss the potential of newer methods, such as patient-reported outcomes and composite measurements that combine data from multiple sources.

Transcatheter aortic valve implantation (TAVI) is now routinely performed in patients with aortic stenosis with low mortality and complication rates. Although periprocedural risks have been substantially minimized, procedure- and contrast-induced acute kidney injury (AKI) remains a major concern. AKI remains a frequent complication of contrast-guided interventional procedures and is associated with a significantly adverse prognosis. We review the currently available clinical data related to AKI, with emphasis on contrast-induced nephropathy (CIN), and discuss a novel, integrated approach aiming to minimize AKI risk in high-risk patients. A stepwise algorithm is also proposed for the management of these complex patients.

We have been studying the role of Hexamethylene bisacetamide (HMBA) Induced Protein 1 (HEXIM1) as a tumor suppressor whose expression is decreased in breast and prostate cancer. The anti-cancer actions of HEXIM1 in melanomas and AML have been reported by other groups. Previous studies have shown that 5-Aza-2′deoxycytidine (5-AzadC), a DNMT1 inhibitor, induces re-expression of tumor suppressor genes by removing/erasing methylation marks from their promoters. Our studies highlighted another mechanism wherein 5-AzadC induced DNA damage, which then resulted in enhanced occupancy of NF-ĸB, P-TEFb, and serine 2 phosphorylated RNA Polymerase II on the HEXIM1 gene. As a consequence, 5-AzadC induced HEXIM1 expression in prostate cancer cell lines and triple negative breast cancers. 5-AzadC-induced DNA damage enhanced P-TEFb occupancy via a mechanism that involved activation of ATR and ATM and induction of NF-ĸB recruitment to the HEXIM1 promoter. Downregulation of NF-ĸB attenuated 5-AzadC-induced HEXIM1 expression in prostate and breast cancer cells. The functional relevance of 5-AzadC-induced HEXIM1 expression is revealed by studies showing the HEXIM1 is required for the induction of apoptosis. Collectively, our findings support a non-epigenetic mechanism for 5-AzadC-induced re-expression of HEXIM1 protein, and may contribute to the clinical efficacy of 5-AzadC.

First humanoid coronavirus was discovered in the middle of 1960s, the class of viruses are considered to be a huge threat. The first onset of human coronavirus, SARS (SARS-CoV) appeared in 2003 which spanned five continents having lethal effects on human population accompanied by The Middle East Respiratory Syndrome Coronavirus in 2012 with a death rate of 35%. The viruses remain a threat till date and are of serious concern since no vaccine or specified drug therapy has been approbated for treating human coronaviruses. The viruses became a pandemic worldwide with the emergence of Wuhan coronavirus (2019-nCoV). SARS-CoV2 viral manifestation poses a serious human life risk by causing acute lung injury and various respiratory outcomes and has become a global concern. High pathogenicity and transmission rate of the viral strain has become the spotlight of research community throughout the world. With the ongoing studies on viral structure and host interactions, the intricacy of the viral proteome structure and replication cycle proposes a need to explore our understanding of host factors playing role in viral multiplication cycle. This review provides insight into our prevalent perception of coronavirus-host interactions, structure of SARS-CoV2, receptor mediated entry of virus inside the human cells, ongoing clinical trials and drug therapies and treatments that are being used to combat COVID-19 targeting viral fusion, replication and its multiplication., Highlights • SARS-CoV2 viral infection poses a serious human life risk by causing acute lung injury • Various medical interventions are being studied for COVID-19. • Introducing anti ACE2 antibodies • Antibodies developed during SARS-CoV infection

Highlights • Pregnant women infected with Ebola virus may present atypically. • Current Ebola virus disease case definitions are inappropriate for pregnant women. • Infected newborns may appear asymptomatic despite being potentially infectious. • Obstetric care during an Ebola outbreak requires heightened precautions. • Pregnant contacts of Ebola-infected individuals require special considerations., Background Between December 2013 and June 2016, West Africa experienced the largest Ebola virus disease (EVD) outbreak in history. Understanding EVD in pregnancy is important for EVD clinical screening and infection prevention and control. Methods We conducted a review of medical records and EVD investigation reports from three districts in Sierra Leone. We report the clinical presentations and maternal and fetal outcomes of six pregnant women with atypical EVD, and subsequent transmission events from perinatal care. Results The six women (ages 18–38) were all in the third trimester. Each presented with signs and symptoms initially attributed to pregnancy. None met EVD case definition; only one was known at presentation to be a contact of an EVD case. Five women died, and all six fetuses/neonates died. These cases resulted in at least 35 additional EVD cases. Conclusions These cases add to the sparse literature focusing on pregnant women with EVD, highlighting challenges and implications for outbreak control. Infected newborns may also present atypically and may shed virus while apparently asymptomatic. Pregnant women identified a priori as contacts of EVD cases require special attention and planning for obstetrical care.

Since the discovery of DNA intercalating agents (by Lerman, 1961), a growing number of organic, inorganic, and metallic compounds have been developed to treat life-threatening microbial infections and cancers. Fused-heterocycles are amongst the most important group of compounds that have the ability to interact with DNA. DNA intercalators possess a planar aromatic ring structure that inserts itself between the base pairs of nucleic acids. Once inserted, the aromatic structure makes van der Waals interactions and hydrogen-bonding interactions with the base pairs. The DNA intercalator may also contain an ionizable group that can form ionic interactions with the negatively charged phosphate backbone. After the intercalation, other cellular processes could take place, leading ultimately to cell death. The heterocyclic nucleus present in the DNA intercalators can be considered as a pharmacophore that plays an instrumental role in dictating the affinity and selectivity exhibited by these compounds. In this work, we have carried out a revision of small organic molecules that bind to the DNA molecule via intercalation and cleaving and exert their antitumor activity. A general overview of the most recent results in this area, paying particular attention to compounds that are currently under clinical trials, is provided. Advancement in spectroscopic techniques studying DNA interaction can be examined in-depth, yielding important information on structure-activity relationships. In this comprehensive review, we have focused on the introduction to fused heterocyclic agents with DNA interacting features, from medicinal point of view. The structure-activity relationships points, cytotoxicity data, and binding data and future perspectives of medicinal compounds have been discussed in detail.

About 14.2% of women in the general Indian population and 4.8% in Delhi use tobacco but its use among women with Major Mental Illness (MMI) in developing countries has not been adequately studied. We assessed tobacco use in women with MMI in a tertiary care psychiatry outpatient department through a cross-sectional, observational study, with sample size of at least n= 77 each for schizophrenia-SZ, bipolar disorder-BD and Recurrent Depressive Disorder-RDD. Fagerstrom Test for Nicotine Dependence (FTND) both for smoke and smokeless tobacco were applied along with a subset of questions from Global Adult Tobacco Survey 2016. After diagnosis and referral by the treating psychiatrist and written informed consent, in our total sample of 321 women participants, lifetime use of tobacco was reported by 14.64%. Of all those who had ever used tobacco, 12.14% used it currently as well. As for diagnosis, those with BD (16.25%) used tobacco most frequently followed by SZ (14.18%) and RDD (6%). The FTND score was higher for schizophrenia indicating greater dependence. Tobacco use among women with MMI was thrice as common as women in general population of Delhi State, with smoke and smokeless tobacco use being equally prevalent, a grave cause for concern and intervention.

Psychotic Like Experiences (PLEs) have been reported in several cultures. The 16 item Launay-Slade Hallucination Scale-Extended (LSHS-E) measures hallucination like experiences (HLEs) in the general population. This study investigated the psychometric properties and the factor structure of LSHS-E Hindi among healthy adults of Delhi. LSHS-E was translated from English to Hindi and then back to English. It was administered as a paper pencil questionnaire to 182 adults from the general population. Reliability of LSHS-E Hindi was measured using Cronbach's alpha and factor structure was established using confirmatory factor analysis (CFA). It was tested against the Community Assessment of Psychic Experiences (CAPE-42) for convergent and divergent validity. Latent Class Analysis (LCA) was performed to identify subgroups with different endorsement of HLEs. Among 182, 18 participants reporting mental and neurological disorders were excluded. LSHS-E Hindi had good reliability (0.85; 95% CI: 0.82 to 0.88). CFA of Hindi LSHS-E revealed the a priori four-factor solution to be best, namely: 'intrusive thoughts', 'vivid daydreams', 'multisensory HLEs', 'auditory and visual HLEs'. LSHS-E Hindi showed stronger correlation with positive domain of CAPE than with negative and depression domains. LCA revealed three classes: low, intermediate and high endorsement of HLEs. Participants with highest endorsement of HLEs were less educated and had highest endorsement on all CAPE dimensions. LSHS-E Hindi has good psychometric properties and can be used to study HLEs in Indians. The four-factor structure model depicts the multidimensionality of HLEs, with 'intrusive thoughts' being the most commonly reported HLE in the sample. LCA supports the continuum hypothesis of HLEs.

Background Transcatheter pulmonary valve replacement (TPVR) is increasingly utilized to address residual or recurrent right ventricular outflow tract pathology in congenital heart disease patients. We aimed to evaluate clinical outcomes and resource utilization comparing TPVR to surgical pulmonary valve replacement (SPVR) for this patient population. Methods From January 2010 until December 2015, 224 patients underwent pulmonary valve replacement (SPVR = 100 and TPVR = 124). These groups were assessed and compared for survival, reoperation, reintervention (surgical or catheter based), hospital costs, and hemodynamic performance. Results There were no mortalities in either group. Despite SPVR patients being significantly younger (12 ± 7 years of age versus 19 ± 13 years of age; p Conclusions Hemodynamic performance is similar between SPVR and TPVR with similar rates of reintervention. While SPVR patients have a longer hospital length of stay, TPVR was associated with higher rates of infective endocarditis, hospital costs, and failure to implant.

Acute changes to left ventricular (LV) hemodynamics after transcatheter aortic valve replacement (TAVR) in humans have been sparsely investigated and informed largely by computer simulation of hypothetical pressure-volume (PV) loops. PV loops are the gold standard for evaluating mechanical

Background Common pesticides used in the region by agricultural workers may cause contact allergy. Methods Thirty agricultural workers with a history of pesticide exposure and dermatitis involving the face, neck, trunk or extremities, and 20 controls comprising 2 groups of 10 subjects each, group 1 with dermatitis and no exposure to pesticides, and group 2 with neither exposure to pesticides nor dermatitis, were patch tested with 10 pesticides commonly used in the region by use of the Finn Chamber method. Results The 30 patients, 20 of whom were male, aged 30-77 years, had dermatitis for 1 month to 18 years, with relapses and remissions. Seasonal exacerbation was present in 18 patients. Six patients attributed aggravation of their dermatitis to pesticide exposure, and 2 of these reacted positively to propiconazole. Positive patch test reactions to pesticides occurred in 10 patients, but not in controls. Thiuram was the commonest sensitizer (4 patients). Three patients were sensitized to propiconazole, and 2 patients reacted positively to metaldehyde. Formaldehyde, mercaptobenzothiazole, cypermethrin and isoproturon gave positive reactions in 1 patient each. Conclusion The sensitizing potential of pesticides remains a concern. Apparently, pesticide contact dermatitis is more common than expected, but remains under-reported, as the implicated pesticides vary across regions and according to the crop patterns.

The design, synthesis and biological evaluation of a library of 1,2,3-triazole carboxylates incorporating carboxylic acid, hydroxymethyl, carboxylic acid hydrazide, carboxamide and benzenesulfonamide moieties is disclosed. All the novel compounds were investigated for their inhibition potential against carbonic anhydrase (CA, EC 4.2.1.1) human (h) isoforms hCA I, II, IV and IX, well established drug targets. The cytosolic isoform hCA I was inhibited with Ki's ranging between 53.2 nM and 7.616 μM whereas the glaucoma associated cytosolic isoform hCA II was inhibited with Ki's in the range 21.8 nM-0.807 μM. The membrane bound isoform hCA IV, involved in glaucoma and retinitis pigmentosa among others, was effectively inhibited by some of these compounds with Ki

Aim The placement of composite in teeth is not an easy task and it poses many challenges. Microleakage is one of the factors that affects the success of any composite restoration. It influences the longevity of dental restorations. The present study was aimed to evaluate and compare microleakage of two restorative composites resins in class II cavities using confocal laser scanning microscopy (CLSM). Materials and methods This was an in vitro study, which included 20 permanent mandibular first molar. On each tooth, 40 class II cavities were prepared with a carbide bur. The teeth were then randomly divided into two groups of 10 each. Group I included teeth in which SonicFill Bulk Fill composite was used. Group II included teeth in which Tetric EvoCeram Bulk Fill composite was used. The microleakage was measured using confocal microscopy at 10* magnification in the fluorescent mode by a scoring system. Results Estimation was done at cervical and occlusal levels, wherein group I included 10 teeth which were restored with SonicFill Bulk Fill composite and group II included 10 teeth which were restored with Tetric EvoCeram Bulk Fill composite. Microleakage was quantified on scoring basis, which was consecutively based on the dye penetration at different levels. Data thus obtained statistically revealed that microleakage was comparatively more in group II as compared with group I. In addition, it was somewhat similar on both cervical as well as occlusal regions. The difference was significant (p = 0.05). Comparison was also done at cervical and occlusal levels using Wilcoxon signed-rank test, which showed significant levels of differences (p > 0.05). Conclusion There is more microleakage in Tetric EvoCeram Bulk Fill composite as compared with SonicFill Bulk Fill composite. Clinical significance No material seems to totally eliminate microleakage in class II situations with gingival margin ended in dentine. However, CLSM is a useful tool in microleakage evaluation that could be used successfully to estimate the severity of microbial penetrations and material of choice as well.

The Center for Medicaid and Medicare Services penalizes hospitals with high readmission rates after coronary artery bypass grafting (CABG). Home health care (HHC) is a proven discharge support tool. We performed a propensity-matched analysis to determine impact of HHC on readmissions after CABG.We queried the National Readmissions Database (January 2012-December 2014) for patients undergoing isolated CABG discharged home with and without HHC. Primary end point was 30-day readmission. A well-balanced subset of patients with and without HHC was created with propensity matching. Weight-adjusted logistic regression was performed to determine impact of HHC on readmissions after CABG.In our study, 204,184 patients (mean age. 64 years; 22% female) were discharged home after CABG; 86,206 (42%) received HHC. Old age (66 vs 63 years; P .01), diabetes (46% vs 41%; P .001), COPD (21% vs 18%; P .01), peripheral arterial disease (14% vs 11%; P .001), and chronic kidney disease (2% vs 1.5%; P = .01) were factors associated with HHC. With nearest-neighbor 1:1 matching without replacement, we identified 66,610 patient pairs (unweighted) for further analysis. Readmission occurred in 11.1% and 12.5% of patients with and without HHC, respectively. After adjustment for 21 clinical covariates, use of HHC (odds ratio, 0.816; 95% confidence interval, 0.808-0.823) led to significantly lower readmission rates (P .001).HHC after coronary artery bypass surgery is more often provided to women, older patients, and those with diabetes mellitus, peripheral arterial disease, and chronic lung or kidney dysfunction. HHC appears to be associated with reduced rates of early readmission.

We describe four cases of histoplasmosis indigenous to Himachal Pradesh (India) that will be of considerable public health interest. A 48-year-old human immunodeficiency virus (HIV)-negative man with cervical and mediastinal lymphadenopathy, hepatosplenomegaly, adrenal mass, and bone marrow involvement was treated as disseminated tuberculosis without benefit. Progressive disseminated histoplasmosis was diagnosed from the fungus in smears from adrenal mass. Another 37-year-old HIV-positive man was on treatment of suspected pulmonary tuberculosis. He developed numerous erythema nodosum leprosum-like mucocutanous lesions accompanied by fever, generalized lymphadenopathy, and weight loss. Pulmonary histoplasmosis with cutaneous dissemination was diagnosed when skin lesions showed the fungus in smears, histopathology, and mycologic culture. Both were successfully treated with amphotericin B/itraconazole. Third patient, a 46-year-old HIV-negative man, had oropharyngeal lesions, cervical lymphadenopathy, intermittent fever, hepatosplenomegaly, and deteriorating general health. Progressive disseminated oropharyngeal histoplasmosis was diagnosed from the fungus in smears and mycologic cultures from oropharyngeal lesions and cervical lymph node aspirates. He died despite initiating treatment with oral itraconazole. Another 32-year-old man 3 months after roadside trauma developed a large ulcer with exuberant granulation tissue over left thigh without evidence of immunosuppression/systemic involvement. He was treated successfully with surgical excision of ulcer under amphotericin B/itraconazole coverage as primary cutaneous histoplasmosis confirmed pathologically and mycologically. A clinical suspicion remains paramount for early diagnosis of histoplasmosis particularly in a nonendemic area. Most importantly, with such diverse clinical presentation and therapeutic outcome selection of an appropriate and customized treatment schedule is a discretion the treating clinicians need to make.

Addressing multidrug resistant stage of breast cancer is an impediment for chemotherapy. Moreover, breast cancer chemotherapy has potential enduring confrontations i.e. related toxicity including effect on fertility of young female patients. The co-delivery of polyphenolic bio-enhancers with oleanolic acid in chitosan coated PLGA nanoparticles was designed for oral delivery with enhanced antitumor effect consecutively preserving the female fertility. The optimized oleanolic- bio-enhancer nano formulation CH-OA-B-PLGA with particle size was 342.2±3.7nm and zeta potential of 34.2±3.1mV was capable of lowering viability in MDAMB 231 cell line 16 times than OA. Further, mechanistic studies in MDAMB-231 cells revealed that CH-OA-PLGA induces apoptosis by mitochondrial membrane disruption; follows ROS mediated and caspase dependent apoptosis. The antitumor effect studied in 4-T1 induced Balb/c mice mammary tumor model displayed augmented antitumor potency by CH-OA-B-PLGA in comparison to OA. In the in vivo toxicity on Sprague-Dawley rat model, CH-OA-B-PLGA significantly displayed the safe profile and also preserves fertility in female rats. The experiment result suggests co-delivery of oleanolic acid with bio-enhancers as a breakthrough for developing safe chemotherapy for hormone independent breast cancer therapy countering the toxicity issues.

Objective Previous studies have suggested an association between dry eye and migraine. In a busy ophthalmologist clinic, quick identification of dry eye in migraine sufferers may improve their quality of life. Tear osmolarity is an objective and reliable tool for diagnosing dry eye. It has not been investigated in any population with migraine. Using tear osmolarity and questionnaires, we aimed to explore the relationship between dry eye and clinical symptoms in patients with migraine. Design Prospective cross-sectional study. Participants Thirty-four adults with migraine sequentially recruited from a single neurologist’s practice. Methods Patients were assessed for subjective and objective signs of migraine and dry eye by using the Migraine Disability Assessment Score, the Ocular Surface Disease Index, and tear osmolarity (TearLab). Headache characteristics were compared by using χ 2 , Fisher’s exact, and Mann-Whitney U tests. Osmolarity scores were compared with scores for headache features. Results Median age of patients was 38 years, and 76.5% were females. Severe migraine disability was reported in 75.6%, and 34.5% reported moderate to severe dry eye symptoms. Objectively, 49.5% had evidence of dry eye, significantly higher than the 20% recognized in the general population ( p p = 0.02). Those with daily headaches were also more likely to have higher tear osmolarity with marginal significance (median osmolarity 310 mOsm/L vs 299 mOsm/L; p = 0.08). Conclusions Patients with migraine, especially those with aura, appear more likely to have dry eye, as indicated by tear osmolarity. Tear osmolarity may also be greater in those who suffer from daily headaches.

A series of seventeen piperazine derivatives have been synthesized and biologically evaluated for the management of andropause-associated prostatic disorders and depression. Five compounds 16, 19, 20, 21 and 22 significantly inhibited proliferation of androgen-sensitive LNCaP prostatic cell line with EC50 values of 12.4 μM, 15.6 μM, 11.8 μM, 10.4 μM, 12.2 μM respectively and decreased Ca2+ entry through adrenergic-receptor α1A blocking activity. Anti-androgenic behaviour of compound 19 and 22 was evident by decreased luciferase activity. The high EC50 value in AR-negative cells PC3 and DU145 suggested that the cytotoxicity of compounds was due to AR down regulation. Compound 19 reduced the prostate weight of rats by 53.8%. Further, forced-swimming and tail-suspension tests revealed antidepressant-like activity of compound 19, lacking effects on neuromuscular co-ordination. In silico ADMET predictions revealed that the compound 19 had good oral absorption, aqueous solubility, non-hepatotoxic and good affinity for plasma protein binding. Pharmacokinetic and tissue uptake of 19 at 10 mg/kg demonstrated an oral bioavailability of 35.4%. In silico docking studies predicted similar binding pattern of compound 19 on androgen receptor as hydroxyflutamide. Compound 19 appears to be a unique scaffold with promising activities against androgen associated prostatic disorders in males like prostate cancer and BPH and associated depression.