Potential role of microRNAs in personalized medicine against hepatitis: a futuristic approach.

MicroRNAs (miRNAs) have been the subject of extensive research for many years, primarily in the context of diseases such as cancer. However, our appreciation of their significance in viral infections, particularly in hepatitis, has increased due to the discovery of their association with both the host and the virus. Hepatitis is a major global health concern and can be caused by various viruses, including hepatitis A to E. This review highlights the key factors associated with miRNAs and their involvement in infections with various viruses that cause hepatitis. The review not only emphasizes the expression profiles of miRNAs in hepatitis but also puts a spotlight on their potential for diagnostics and therapeutic interventions. Ongoing extensive studies are propelling the therapeutic application of miRNAs, addressing both current limitations and potential strategies for the future of miRNAs in personalized medicine. Here, we discuss the potential of miRNAs to influence future medical research and an attempt to provide a thorough understanding of their diverse roles in hepatitis and beyond.

Does the Gender of Doctors Change a Patient's Perception?

In the past, researchers have used various data sources like social media, admission applications, or letters of recommendation to identify gender-based differences in linguistic data. One such avenue in healthcare is the online physician reviews website. Such websites, for example, RateMyDoctors.com, ZocDoc, or even Yelp.com have become a go-to place for patients when choosing their physicians. In the current research, we used two different natural language processing (NLP) approaches: semi-supervised and unsupervised topic modeling to analyze the text of the reviews to identify gender-based linguistic differences from patients' perspectives. We found that female physicians receive more reviews on their personable skills and warmth, aligning with the Stereotype Content Model. We also found other popular topics discussing bedside manners and overall patient experiences, where the reviews suggested that patients were happier with their experience with female physicians and perceived them to have more positive traits than their male counterparts. Although our study did not reflect significant linguistic differences; it highlights the importance for patients and doctors to be more aware of potential gender stereotypes and perceptions.

Tailored one anastomosis gastric bypass - Subgroup analysis of a randomised control trial based on bilio-pancreatic limb length with long-term results of 101 patients.

Background: : Ideal bilio-pancreatic limb (BPL) length is a highly debatable issue in one anastomosis gastric bypass (OAGB). Whether to use a tailored BPL or a fixed-length BPL needs to be answered. Materials and Methods: : One-hundred and one patients who have undergone tailored OAGB based on basal metabolic index (BMI) and type 2 diabetes mellitus (T2DM) were analysed. Sixty-three patients had BPL of 150 cm and 38 patients had BPL of 180 cm. Mean pre-operative BMI of BPL 150 and 180 cm groups were 39.73 and 51.92 kg/m2, respectively. Results: There was a significant drop in mean total body weight, BMI and excess body weight of both the groups at 1 year which persisted for 5 years post-operatively. The mean BMI of BPL 150 and BPL 180 cm group at 5 years was 29.17 and 32.88 kg/m2, respectively. Although mean percentage excess weight loss (%EWL) and percentage of excess BMI loss in the two groups was similar, the mean percentage total weight loss (%TWL) was significantly higher for the BPL 180 cm group. There was no difference between the two groups in the number of patients who had >50% EWL and >20% TWL. At 5 years of follow-up, the mean serum iron level was significantly low in BPL 180 cm group. There was a significant drop in mean haemoglobin A1c values postoperatively, with no difference between the two groups. Conclusions: Tailored BPL of 150 and 180 cm do not show any difference in the number of patients achieving >50% EWL or >20% TWL and so increasing limb length may not increase the number of good responders for weight loss. Although the resolution of T2DM and improvement of QoL score do not change significantly with increase in BPL length, mean serum iron levels may be lower with longer BPL.

Impact of Bacillus licheniformis SV1 Derived Glycolipid on Candida glabrata Biofilm.

In the present investigation, we have evaluated the antibiofilm potential of Bacillus licheniformis SV1 derived glycolipid against C. glabrata biofilm. Impact of isolated glycolipid on the viability of C. glabrata and on inhibiting as well as eradicating ability of its biofilm were studied. Further, morphological alterations, reactive oxygen species generation (ROS) production and transcriptional expression of selected genes (RT-PCR) of C. glabrata in response with isolated glycolipid were studied. The isolated glycolipid (1.0 mg ml-1) inhibited and eradicated C. glabrata biofilm approximately 80% and 60%, respectively. FE-SEM images revealed glycolipid exposure results in architectural alteration and eradication of C. glabrata biofilm and ROS generation. Transcriptional studies of selected genes showed that the expression of AUS1, FKS1 and KRE1 were down-regulated, while that of ergosterol biosynthesis pathway and multidrug transporter increased, in the presence of glycolipid.

New therapeutic activity of metabolic enhancer piracetam in treatment of neurodegenerative disease: Participation of caspase independent death factors, oxidative stress, inflammatory responses and apoptosis.

Piracetam, a nootropic drug that has been clinically used for decades but remains enigmatic due to no distinct understanding of its mechanism of action. The present study aimed to investigate the role of caspase independent pathway in piracetam mediated neuroprotection. LPS administration caused significant alterations in oxidative stress related parameters like glutathione, glutathione reductase and increased lipid peroxidation. LPS administration also caused augmented expression of inflammatory cytokines and astrocytes activation. Piracetam treatment offered significant protection against LPS induced oxidative and inflammatory parameters and inhibited astrocytes activation. LPS administration caused augmented level of reactive oxygen species and depleted mitochondrial membrane potential which were attenuated with piracetam treatment. This study for the first time demonstrates the role of caspase independent death factors in piracetam induced neuroprotective effects in rat brain. Translocation of mitochondrial resident apoptosis inducing factor and endonuclease G to nucleus through cytosol after LPS administration was significantly blocked with piracetam treatment. Further, LPS induced DNA fragmentation along with up regulated Poly [ADP-ribose] polymerase 1 (PARP1) levels were also inhibited with piracetam treatment. Apoptotic death was confirmed by the cleavage of caspase 3 as well as histological alteration in rat brain regions. LPS administration caused significantly increased level of cleaved caspase 3, altered neuronal morphology and decreased neuronal density which were restored with piracetam treatment. Collectively our findings indicate that piracetam offered protection against LPS induced inflammatory responses and cellular death including its antioxidative antiapoptotic activity with its attenuation against mitochondria mediated caspase independent pathway.

Neglected and locked anterior shoulder dislocation: functional outcomes and complications after open reduction and preservation of humeral head.

Background: Neglected and locked anterior shoulder dislocation is a rare problem that presents several treatment challenges. Our study aimed to evaluate the functional outcomes and postoperative complications after open reduction and head preservation surgery in patients with neglected and locked anterior shoulder dislocation. Methods: Ten patients (age 51 ± 22 years) with a follow-up of 27 months ± 7 months (range 24-40 months) were included in the study. The anteriorly dislocated humeral heads were open and reduced after an average neglect of 10 ± 15 months. The neglected dislocation was classified into two types by the severity of the injury. (1) Type 1: There were no associated severe injuries, and the humeral head was reduced in the glenoid cavity without take-down of the subscapularis (type 1a) (n = 5) or via take-down of the upper half of the subscapularis (type 1b) (n = 2). (2) Type 2: There were associated factors such as a greater tuberosity fracture (n = 2) or a grade 3/4 fatty infiltrated supraspinatus and infraspinatus muscles (n = 1). Complete removal of the subscapularis was necessary to reduce the humeral head. Results: The pain scores improved from a baseline value of 8 ± 1 to a final value of 1 ± 1 (P < .001), the absolute Constant score improved from a baseline value of 13 ± 8 to a final value of 69 ± 21 (P < .001), elevation range of motion (ROM) improved from a baseline value of 44° ± 43° to a final value of 123° ± 30° (P < .001), external rotation ROM improved from 0° ± 13° to 49° ± 12° (P < .001), and internal rotation ROM improved from sacroiliac joint ± 2 vertebra level to thoracic T11 ± 3 vertebrae level (P < .0001). The final shoulder subjective value was 77 ± 20 and was excellent in 3 patients, good in 5 patients, fair in 1, and poor in 1 patient. Major complications were observed in 30% (n = 3) of patients: persistent humeral head anterior subluxation in 20% (n = 2) of patients and superior migration of the humeral head in 10% (n = 1) of patients. Conclusion: Open reduction and head preservation in patients with neglected anterior dislocation led to good functional outcomes in 70% (as per Constant score) to 80% (as per shoulder subjective value) of the patients. However, we observed major complications such as persistent anterior subluxation (n = 2) and superior head migration (n = 1), leading to suboptimal functional outcomes in cases with associated factors such as a greater tuberosity fracture or severe fatty infiltrated cuff muscles.

Frozen shoulder after COVID-19 vaccination versus idiopathic frozen shoulder: similar clinical features and functional improvement at 1-year follow-up.

Background: Frozen shoulder after COVID-19 vaccination is sparsely discussed in the medical literature. We aimed to evaluate: (1) the differences in the baseline clinical features and functional outcomes of conservatively treated frozen shoulder following COVID-19 vaccination compared to idiopathic frozen shoulder (2) the improvements in pain scores, functional outcomes, and range of motion (ROM) at 6-10 months and at 1 year of follow-up in patients with frozen shoulder after COVID-19 vaccination treated by conservative therapy. Methods: Between June 2021 and December 2021, 12 patients (13 shoulders) that were diagnosed with frozen shoulder after COVID-19 vaccination (vaccine related frozen shoulder [VRF] group) (final follow-up of 12.4 months ± 0.8 months) were compared with 20 patients that were diagnosed as idiopathic frozen shoulder unrelated to vaccination (unvaccinated frozen shoulder [UFS] group) (average follow-up of 13.4 ± 3.1 months). All patients were treated with home-based stretching exercises. Four (33%) patients in the VRF group and 15 (75%) patients in the UFS group underwent steroid injection in the suprascapular notch by an experienced radiologist. Results: The left side was affected more frequently in the VRF group [n = 10 (83.3%)] than in the UFS group [n = 8 (40%), P = .03]. The VRF and the UFS groups were similar in the rest of the baseline clinical features, such as the age distribution, men/women ratio, baseline Oxford Shoulder Scores (OSS), ROM deficit, and pain visual analogue scale (VAS) scores. The OSS, VAS pain scores, and the ROM deficit significantly improved in the VRF group at the 6-10-month follow-up and then at the final (12.4 ± 0.8 months) follow-up compared to the baseline values. At the final follow-up, there were no significant differences in the average external rotation, external rotation deficit, elevation, elevation deficit, internal rotation, pain VAS scores, and OSS between the VRF and the UFS group. Conclusion: To conclude, frozen shoulder following COVID-19 vaccination may present with clinical features similar to those of the idiopathic frozen shoulder. Furthermore, the patients with frozen shoulder following COVID-19 vaccination may continue to improve over one year with conservative treatment; the final improvements in function and ROM are similar to those with idiopathic frozen shoulder.

LSG vs OAGB: 7-Year Follow-up Data of a Randomised Control Trial and Comparative Outcome Based on BAROS Score.

BACKGROUND: This study aims to evaluate and compare long-term results of laparoscopic sleeve gastrectomy (LSG) and one anastomosis gastric bypass (OAGB) based on bariatric analysis reporting and outcome system (BAROS) score. MATERIALS AND METHODS: Patients operated for morbid obesity between 2013 and 2015 were randomised to LSG and OAGB groups. Based on inclusion and exclusion criteria, 201 patients (100 LSG and 101 OAGB) were analysed for changes in total body weight (TBW), body mass index (BMI), percent excess weight loss (%EWL), percent total weight loss (%TWL), QoL (quality of life) scores, comorbidity resolution and outcome based on BAROS at 7 years. RESULTS: Sixty-six LSG and 64 OAGB patients were followed up at 7 years. Mean pre-operative TBW and BMI were 119 ± 28.2 and 44.87 ± 7.71 for LSG group and 113.25 ± 23.74 and 44.71 ± 8.75 for OAGB group respectively. At 7 years after surgery, there was significant drop in mean TBW and BMI in both groups. Mean %EWL for LSG and OAGB patients was 50.78 ± 28.48 and 59.99 ± 23.32 and mean %TWL for LSG and OAGB patients was 23.22 ± 12.66 and 27.71 ± 12.27 respectively. Mean QoL scores at 7 years were significantly higher than the pre-operative scores and most of the patients in both groups had remission or improvement in their comorbidities. 68.76% OAGB patients had very good or excellent outcome on BAROS score while only 36.37% LSG patients had similar outcome. CONCLUSIONS: LSG and OAGB are successful bariatric procedures over the long term. OAGB outperforms LSG and has significantly higher %EWL and %TWL over the long term.

Feasibility, safety and effectiveness of the enhanced recovery after surgery protocol in patients undergoing liver resection.

Backgrounds/Aims: The implementation of enhanced recovery after surgery (ERAS) protocols has demonstrated significant advantages for patients by mitigating surgical stress and expediting recovery across a spectrum of surgical procedures worldwide. This investigation seeks to assess the effectiveness of the ERAS protocol specifically in the context of major liver resections within our geographical region. Methods: Our department conducted retrospective analysis of prospectively collected data, gathered from consenting individuals who underwent liver resections from January 2018 to December 2023. The assessment encompassed baseline characteristics, preoperative indications, surgical outcomes, and postoperative complications among patients undergoing liver surgery. Results: Among the included 184 patients (73 standard care, 111 ERAS program), the baseline characteristics were similar. Median postoperative hospital stay differed significantly: 5 days (range: 3-13 days) in ERAS, and 11 days (range: 6-22 days) in standard care (p < 0.001). Prophylactic abdominal drainage was less in ERAS (54.9%) than in standard care (86.3%, p < 0.001). Notably, in ERAS, 88.2% initiated enteral feeding orally on postoperative day 1, significantly higher than in standard care (47.9%, p < 0.001). Early postoperative mobilization was more common in ERAS (84.6%) than in standard care (36.9%, p < 0.001). Overall complication rates were 21.9% in standard care, and 8.1% in ERAS (p = 0.004). Conclusions: Our investigation highlights the merits of ERAS protocol; adherence to its diverse components results in significant reduction in hospital length of stay, and reduced occurrence of postoperative complications, improving short-term recovery post liver resection.

Rotenone-induced apoptosis and role of calcium: a study on Neuro-2a cells.

Rotenone causes cytotoxicity in astrocytic cell culture by glial activation, which is linked to free radical generation. The present study is an investigation to explore whether rotenone could also cause cellular toxicity in mouse neuroblastoma cells (Neuro-2a) under treatment similar to astroglial cells. The effect of rotenone (0.1, 1, and 10 µM) on mitochondrial dehydrogenase enzyme activity by MTT reduction assay, PI uptake, total reactive oxygen species (ROS)/superoxide levels, nitrite levels, extent of DNA damage (by comet assay), and nuclear morphological alteration by Hoechst staining was studied. Caspase-3 and Ca⁺²/calmodulin-dependent protein kinase II (CaMKIIα) gene expression was determined to evaluate the apoptotic cell death and calcium kinase, respectively. Calcium level was estimated fluorometrically using fura-2A stain. Rotenone decreased mitochondrial dehydrogenase enzyme activity and generated ROS, superoxide, and nitrite. Rotenone treatment impaired cell intactness and nuclear morphology as depicted by PI uptake and chromosomal condensation of Neuro-2a cells, respectively. In addition, rotenone resulted in increased intracellular Ca⁺² level, caspase-3, and CaMKIIα expression. Furthermore, co-exposure of melatonin (300 µM), an antioxidant to cell culture, significantly suppressed the rotenone-induced decreased mitochondrial dehydrogenase enzyme activity, elevated ROS and RNS. However, melatonin was found ineffective to counteract rotenone-induced increased PI uptake, altered morphological changes, DNA damage, elevated Ca⁺², and increased expression of caspase-3 and CaMKIIα. The study indicates that intracellular calcium rather than oxidative stress is a major factor for rotenone-induced apoptosis in neuronal cells.

Psychological Analysis for Depression Detection from Social Networking Sites.

Rapid technological advancements are altering people's communication styles. With the growth of the Internet, social networks (Twitter, Facebook, Telegram, and Instagram) have become popular forums for people to share their thoughts, psychological behavior, and emotions. Psychological analysis analyzes text and extracts facts, features, and important information from the opinions of users. Researchers working on psychological analysis rely on social networks for the detection of depression-related behavior and activity. Social networks provide innumerable data on mindsets of a person's onset of depression, such as low sociology and activities such as undergoing medical treatment, a primary emphasis on oneself, and a high rate of activity during the day and night. In this paper, we used five machine learning classifiers-decision trees, K-nearest neighbor, support vector machines, logistic regression, and LSTM-for depression detection in tweets. The dataset is collected in two forms-balanced and imbalanced-where the oversampling of techniques is studied technically. The results show that the LSTM classification model outperforms the other baseline models in the depression detection healthcare approach for both balanced and imbalanced data.

Oral haemangiomas- Series of two case reports and review of management.

Haemangiomas are one of the most common of all human birth defects and are based on vascular tissues. These lesions are mainly identified into two groups which are named as (a) capillary and (b) cavernous haemangioma. Capillary haemangioma consists of small capillary vessels which show lobules formation. Cavernous haemangioma consists of large dilated vessels and they can reach to large sizes. Many treatment modalities are evaluated in which some modalities are successful and some are quite disappointing. Surgical excision, irradiation, CO2 freezing, sclerosing agents, cauterization, steroid therapy and watchful waiting are among the treatment methods evaluated. The treatment plan established for Haemangiomas must consider aspects such as size, location, lesion hemodynamics, patient's age and viability of the technique to be used. In the present series of two case reports, the management of haemangioma was done using two different modalities depending on their presentation so that major complications can be avoided and more attention should be paid to more conservative treatment modalities.

TOXGB: Teamwork Optimization Based XGBoost model for early identification of post-traumatic stress disorder.

Post-traumatic stress (PTSD) is considered a clinical issue that influences numerous people from diverse trades all over the world. Numerous research scholars recorded diverse complexities to estimate the severity of the PTSD symptoms in the patients. But diagnosing PTSD and obtaining accurate diagnosing techniques becomes a more complicated task. Therefore, this paper develops a speech based post-traumatic stress disorder monitoring method and the significant objective of the proposed method is to determine if the patients are affected by PTSD. The proposed approach utilizes three different steps: pre-processing or pre-emphasis, feature extraction as well as classification to evaluate the patients affected by PTSD or not. The input speech signal is initially provided to the pre-processing phase where the speech gets segmented into frames. The speech frame is then extracted and classified using XGBoost based Teamwork optimization (XGB-TWO) algorithm. In addition to this, we utilized two different types of datasets namely TIMIT and FEMH to evaluate and classify the PSTD from the speech signals. Furthermore, based on the evaluation of the proposed model to diagnose PTSD patients, various evaluation metrics namely accuracy, specificity, sensitivity, and recall are evaluated. Finally, the experimental investigation and comparative analysis are carried out and the evaluation results demonstrated that the accuracy rate achieved for the proposed technique is 98.25%.

Integrative Multiomics and Regulatory Network Analyses Uncovers the Role of OAS3, TRAFD1, miR-222-3p, and miR-125b-5p in Hepatitis E Virus Infection.

The hepatitis E virus (HEV) is a long-ignored virus that has spread globally with time. It ranked 6th among the top risk-ranking viruses with high zoonotic spillover potential; thus, considering its viral threats is a pressing priority. The molecular pathophysiology of HEV infection or the underlying cause is limited. Therefore, we incorporated an unbiased, systematic methodology to get insights into the biological heterogeneity associated with the HEV. Our study fetched 93 and 2016 differentially expressed genes (DEGs) from chronic HEV (CHEV) infection in kidney-transplant patients, followed by hub module selection from a weighted gene co-expression network (WGCN). Most of the hub genes identified in this study were associated with interferon (IFN) signaling pathways. Amongst the genes induced by IFNs, the 2'-5'-oligoadenylate synthase 3 (OAS3) protein was upregulated. Protein-protein interaction (PPI) modular, functional enrichment, and feed-forward loop (FFL) analyses led to the identification of two key miRNAs, i.e., miR-222-3p and miR-125b-5p, which showed a strong association with the OAS3 gene and TRAF-type zinc finger domain containing 1 (TRAFD1) transcription factor (TF) based on essential centrality measures. Further experimental studies are required to substantiate the significance of these FFL-associated genes and miRNAs with their respective functions in CHEV. To our knowledge, it is the first time that miR-222-3p has been described as a reference miRNA for use in CHEV sample analyses. In conclusion, our study has enlightened a few budding targets of HEV, which might help us understand the cellular and molecular pathways dysregulated in HEV through various factors. Thus, providing a novel insight into its pathophysiology and progression dynamics.

Comparison of isosorbide mononitrate and misoprostol for cervical ripening in termination of pregnancy between 8 and 12 weeks: a randomized controlled trial.

AIM: The present study was undertaken to compare the efficacy of isosorbide mononitrate (IMN) and misoprostol for cervical ripening in termination of pregnancy between 8 and 12 weeks. MATERIALS AND METHODS: This prospective randomized single blind study enrolled 40 women with singleton pregnancy seeking surgical termination of pregnancy between 8 and 12 weeks of gestation. They were divided into two groups--group I received IMN 40 mg while group II received misoprostol 40 mg vaginally, 3 h prior to suction and evacuation. All women were monitored for effects of cervical ripening and adverse effects. RESULTS: The mean sizes of dilators that could be negotiated without any resistance was 5.9 ± 1.33 in group I and 8.6 ± 0.94 in group II (p < 0.001, 95% CI 0.58, 0.41). The mean dilator sizes at which resistance was first encountered was 6.9 ± 1.37 in group I and 9.9 ± 1.23 in group II (p < 0.001, 95% CI 0.60, 0.54). The mean blood loss was 61.5 ± 13.86 ml in group I and 36.25 ± 12.80 ml in group II (p < 0.001, 95% CI 6.07, 5.63). Headache was the most common adverse effect seen with IMN use. CONCLUSION: The results show that IMN has a definite role and better safety profile than misoprostol in first trimester cervical ripening, although misoprostol is more effective and causes less blood loss.

Cardinal role of eukaryotic initiation factor 2 (eIF2α) in progressive dopaminergic neuronal death & DNA fragmentation: Implication of PERK:IRE1α:ATF6 axis in Parkinson's pathology.

The study was conducted to assess the role of eukaryotic initiation factor 2 (eIF2α) in progressive dopaminergic neuronal death employing various interventions (YM08, 4µ8C, AEBSF, salubrinal, ursolic acid) of endoplasmic reticulum (ER) stress signaling. The protein level of all the ER stress related signaling factors (GRP78, IRE1α, ATF6, eIF2α, ATF4, XBP-1, GADD153) were estimated after 3 and 7 day of experiment initiation. Findings with single administration of interventions showed that salubrinal exhibited significant protection against rotenone induced adverse alterations in comparison to other interventions. Therefore, further study was expanded with repeat dose of salubrinal. Rotenone administration in rat brain caused the significant biochemical alterations, dose dependent progressive neuronal apoptosis and altered neuronal morphology which was significantly attenuated with salubrinal treatment. In conclusion, findings showed that rotenone administration caused the dose dependent progressive neuronal death including cardinal role of eIF2α, suggesting the potential pharmacological utilization of salubrinal or salubrinal like molecules in therapeutics of Parkinson's diseases.

LSG vs MGB-OAGB: 5-Year Follow-up Data and Comparative Outcome of the Two Procedures over Long Term-Results of a Randomised Control Trial.

BACKGROUND: Bariatric surgery is a durable and effective way for the management of obesity and resolution of related comorbidities. The aim of this study is to evaluate the outcome of laparoscopic sleeve gastrectomy (LSG) and one-anastomosis gastric bypass (OAGB) over long term in a South Asian population. MATERIALS AND METHODS: This is a prospective randomised trial comparing the outcome of 100 and 101 LSG and OAGB patients respectively after 5-year follow-up. This study is in continuity with previous published papers with 1- and 3-year follow-up. 71 LSG and 73 OAGB patients followed at 5 years. The results of these patients were analysed and compared in terms of %EWL, comorbidity resolution and quality of life (QoL) at 5 years. Bariatric analysis reporting and outcome system (BAROS) was used to assess the outcome of patients. RESULTS: At 5-year follow-up, both LSG and OAGB patients performed well and patients had significant improvement in BMI (kg/m2). The mean preoperative BMI of LSG and OAGB patients was 44.89 ± 7.94 and 45.32 ± 8.24, and their mean BMI at 5 years was 33.41 ± 6.02, 30.80 ± 3.40 respectively. At 5 years, %EWL was 55.95 ± 27.01 and 65.28 ± 13.98 for LSG and OAGB patients respectively. The QoL score of LSG and OAGB patients was 1.86 ± 0.56 and 2.35 ± 0.41 while comorbidity score was 1.84 ± 0.68 and 2.24 ± 0.62 respectively at 5 years. CONCLUSIONS: Both LSG and OAGB are effective bariatric procedures over long term with respect to weight loss, comorbidity resolution and improvement in QoL. OAGB is significantly better than LSG in all the three parameters at 5 years.

Salubrinal attenuates nitric oxide mediated PERK:IRE1α: ATF-6 signaling and DNA damage in neuronal cells.

The present study was conducted to investigate the effect of salubrinal on nitric oxide mediated endoplasmic reticulum stress signaling and neuronal apoptosis. Rotenone treatment to neuro2a cells caused significantly decreased cell viability, increased cytotoxicity, augmented nitrite levels, increased nitrotyrosine level and augmented level of key ER stress markers (GRP-78, GADD153 and caspase-12). These augmented levels of ER stress markers could be attenuated with pretreatment of nitric oxide synthase inhibitor-aminoguanidine as well as with salubrinal. The rotenone treatment to neuro2a cells also triggered the ER stress induced up regulation of various signaling factors of unfolded protein response involving pPERK, ATF4, p-IRE1α, XBP-1 and ATF-6. Pretreatment of salubrinal significantly attenuated the activation of transmembrane kinases (PERK and IRE1) and ATF6 and restored the rotenone induced altered level of other UPR related signaling factors. Rotenone induced dephosphorylation of eIF2α was also inhibited with salubrinal treatment. Biochemically rotenone treatment to neuro2a cells caused the reactive oxygen species generation, depleted mitochondrial membrane potential and increased intra cellular calcium level which was attenuated with salubrinal treatment. Rotenone treatment to neuro2a cells also caused neuronal apoptosis, DNA fragmentation and chromatin condensation which were attenuated with salubrinal treatment. In conclusion, the findings suggested that rotenone causes the augmented level of nitric oxide which contributes in ER stress and could be inhibited by both aminoguanidine and/or salubrinal treatment. Further, salubrinal treatment attenuates the nitric oxide induced ER stress axis PERK:IRE1α:ATF-6 and inhibits the DNA damage and neuronal apoptosis.

Correction to: Endoplasmic Reticulum Stress Plays a Key Role in Rotenone-Induced Apoptotic Death of Neurons.

The original version of this article unfortunately contained a mistake.

Effectiveness of Phytoactive Molecules on Transcriptional Expression, Biofilm Matrix, and Cell Wall Components of Candida glabrata and Its Clinical Isolates.

Toxicity challenges by antifungal arsenals and emergence of multidrug resistance scenario has posed a serious threat to global community. To cope up with this alarming situation, phytoactive molecules are richest, safest, and most effective source of broad spectrum antimicrobial compounds. In the present investigation, six phytoactive molecules [cinnamaldehyde (CIN), epigallocatechin, vanillin, eugenol (EUG), furanone, and epigallocatechin gallate] were studied against Candida glabrata and its clinical isolates. Among these, CIN and EUG which are active components of cinnamon and clove essential oils, respectively, exhibited maximum inhibition against planktonic growth of C. glabrata at a concentration of 64 and 128 µg mL-1, respectively. These two molecules effectively inhibited and eradicated approximately 80% biofilm of C. glabrata and its clinical isolates from biomaterials. CIN and EUG increased reactive oxygen species generation, cell lysis, and ergosterol content in plasma membrane and reduced virulence attributes (phospholipase and proteinase) as well as catalase activity of C. glabrata cells. Reduction of mitochondrial membrane potential with increased release of cytochrome c from mitochondria to cytosol indicated initiation of early apoptosis in CIN- and EUG-treated C. glabrata cells. Transcriptional analysis showed that multidrug transporter (CDR1) and ergosterol biosynthesis genes were downregulated in the presence of CIN, while getting upregulated in EUG-treated cells. Interestingly, genes such as 1,3-ß-glucan synthase (FKS1), GPI-anchored protein (KRE1), and sterol importer (AUS1) were downregulated upon treatment of CIN/EUG. These results provided molecular-level insights about the antifungal mechanism of CIN and EUG against C. glabrata including its resistant clinical isolate. The current data established that CIN and EUG can be potentially formulated in new antifungal strategies.