Practical Access to Fused Carbazoles via Oxidative Benzannulation and their Photophysical Properties.

An aryne annulation strategy for the synthesis of fused carbazoles is developed using indolyl ß-ketonitrile in a cascade manner. The reaction sequence involves aryne-mediated [2 + 2] cycloaddition cleavage and intramolecular Michael addition, followed by oxidation under transition-metal-free reaction conditions. Subsequently, conversion of benzo[b]carbazole-6-carbonitrile to carbazole quinone is observed upon prolongation of the reaction time. Furthermore, these materials exhibit high quantum efficiency, which promotes the light-emitting diode applications.

Functional Characterization of Alr0765, A Hypothetical Protein from Anabaena PCC 7120 Involved in Cellular Energy Status Sensing, Iron Acquisition and Abiotic Stress Management in E. coli Using Molecular, Biochemical and Computational Approaches.

BACKGROUND: Cyanobacteria are excellent model to understand the basic metabolic processes taking place in response to abiotic stress. The present study involves the characterization of a hypothetical protein Alr0765 of Anabaena PCC7120 comprising the CBS-CP12 domain and deciphering its role in abiotic stress tolerance. METHODS: Molecular cloning, heterologous expression and protein purification using affinity chromatography were performed to obtain native purified protein Alr0765. The energy sensing property of Alr0765 was inferred from its binding affinity with different ligand molecules as analyzed by FTIR and TNP-ATP binding assay. AAS and real time-PCR were applied to evaluate the iron acquisition property and cyclic voltammetry was employed to check the redox sensitivity of the target protein. Transcript levels under different abiotic stresses, as well as spot assay, CFU count, ROS level and cellular H2O2 level, were used to show the potential role of Alr0765 in abiotic stress tolerance. In-silico analysis of Alr0765 included molecular function probability analysis, multiple sequence analysis, protein domain and motif finding, secondary structure analysis, protein-ligand interaction, homologous modeling, model refinement and verification and molecular docking was performed with COFACTOR, PROMALS-3D, InterProScan, MEME, TheaDomEx, COACH, Swiss modeller, Modrefiner, PROCHECK, ERRAT, MolProbity, ProSA, TM-align, and Discovery studio, respectively. RESULTS: Transcript levels of alr0765 significantly increased by 20, 13, 15, 14.8, 12, 7, 6 and 2.5 fold when Anabaena PCC7120 treated with LC50 dose of heat, arsenic, cadmium, butachlor, salt, mannitol (drought), UV-B, and methyl viologen respectively, with respect to control (untreated). Heterologous expression resulted in 23KDa protein observed on the SDS-PAGE. Immunoblotting and MALDI-TOF-MS/MS, followed by MASCOT search analysis, confirmed the identity of the protein and ESI/MS revealed that the purified protein was a dimer. Binding possibility of Alr0765 with ATP was observed with an almost 6-fold increment in relative fluorescence during TNP-ATP binding assay with a λ max of 538 nm. FTIR spectra revealed modification in protein confirmation upon binding of Alr0765 with ATP, ADP, AMP and NADH. A 10-fold higher accumulation of iron was observed in digests of E. coli with recombinant vector after induction as compared to control, which affirms the iron acquisition property of the protein. Moreover, the generation of the redox potential of 146 mV by Alr0765 suggested its probable role in maintaining the redox status of the cell under environmental constraints. As per CFU count recombinant, E. coli BL21 cells showed about 14.7, 7.3, 6.9, 1.9, 3 and 4.9 fold higher number of colonies under heat, cadmium (CdCl2), arsenic (Na3AsO4), salt (NaCl), UV-B and drought (mannitol) respectively compared to pET21a harboring E. coli BL21 cells. Deterioration in the cellular ROS level and total cellular H2O2 concentration validated the stress tolerance ability of Alr0765. In-silico analysis unraveled novel findings and attested experimental findings in determining the role of Alr0765. CONCLUSION: Alr0765 is a novel CBS-CP12 domain protein that maintains cellular energy level and iron homeostasis which provides tolerance against multiple abiotic stresses.

Identification and functional characterization of four novel aldo/keto reductases in Anabaena sp. PCC 7120 by integrating wet lab with in silico approaches.

Aldo/keto reductases (AKRs) constitute a multitasking protein family that catalyzes diverse metabolic transformations including detoxification of stress generated reactive aldehydes. Yet this important protein family is poorly understood particularly in cyanobacteria, the ecologically most diverse and significant group of micro-organisms. Present study is an attempt to characterize all putative AKRs of Anabaena sp. PCC 7120. In silico analysis, it revealed the presence of at least four putative AKRs in Anabaena PCC7120 genome. All four proteins share less than 40% sequence identity with each other and also with the identified members of AKR superfamily and hence deserve to be assigned in new families. Dissimilarity in sequences is also reflected through their substrate specificity. While reduction of trans-2-nonenal, a LPO-derived reactive aldehyde was common across the four proteins, these proteins were found to be activated during heat, salt, Cd, As, and butachlor treatments, and their ectopic expression in Escherichia coli conferred tolerance to the above abiotic stresses. These findings affirm the role of AKRs in providing a broad tolerance to environmental stresses conceivably by detoxifying the stress-generated reactive aldehydes.

A Comparison of the Strength of Association of Reid Colposcopic Index and Swede Score With Cervical Histology.

OBJECTIVE: Colposcopic scoring systems provide an objective diagnosis and select patients who require treatment. A new scoring system, Swede score, has added lesion size as a parameter. This study aimed to compare the strength of association of Reid colposcopic index versus Swede score and assess their utility in low-resource settings. METHODS: In this prospective study, 150 women aged 30 to 59 years with abnormal screening result were enrolled. All women underwent colposcopy; the findings were scored by both Reid colposcopic index and Swede score, biopsy taken from all abnormal areas. Performances of both the scores were calculated. RESULTS: A total of 33 (22%) CIN 2+ lesions were detected. Reid colposcopic index at a cutoff of 5 had sensitivity, specificity, positive predictive value, and negative predictive value for detecting CIN2+ lesions of 96.97%, 95.35%, 88.89%, and 98.8%, respectively. Using Swede score at a cutoff of 8, sensitivity, specificity, positive predictive value, and negative predictive value were 42.42%, 100%, 100%, and 81.9%, and with a cutoff of 5, these were 100%, 88.37%, 76.74%, and 100%, respectively. The correlation coefficient (R) was 0.919. By Spearman rank correlation coefficient, the strength of correlation between Swede score and RCI was 0.937 (p < .001). CONCLUSIONS: Swede score can be used flexibly depending on the setting. The lower threshold (5) with high sensitivity can be used for screening, whereas the higher threshold (8) with high specificity can be used for screen-and-treat selection to decrease the overtreatment rate. Thus, it is a more attractive option for cancer prevention programs in low-resource settings.

Tetanus toxoid-loaded cationic non-aggregated nanostructured lipid particles triggered strong humoral and cellular immune responses.

In the present investigation, non-aggregated cationic and unmodified nanoparticles (TT-C-NLPs4 and TT-NLPs1) were prepared of about 49.2 ± 6.8-nm and 40.8 ± 8.3-nm, respectively. In addition, spherical shape, crystalline architecture and cationic charge were also noticed. Furthermore, integrity and conformational stability of TT were maintained in both TT-C-NLPs4 and TT-NLPs1, as evidenced by symmetrical position of bands and superimposed spectra, respectively in SDS-PAGE and circular dichroism. Cellular uptake in RAW264.7 cells indicating the concentration-dependent internalisation of nanoparticles. Qualitatively, CLSM exhibited enhanced cellular uptake of non-aggregated TT-C-NLPs4 owing to interaction with negatively charged plasma membrane and clevaloe mediated/independent endocytosis. In last, in vivo immunisation with non-aggregated TT-C-NLPs4 elicited strong humoral (anti-TT IgG) and cellular (IFN-γ) immune responses at day 42, as compared to non-aggregated TT-NLPs1 and TT-Alum following booster immunisation at day 14 and 28. Thus, non-aggregated cationic lipid nanoparticles may be a potent immune-adjuvant for parenteral delivery of weak antigens.

Sustained-release protamine sulphate-impregnated microspheres may reduce the frequent administration of recombinant interferon α-2b in ovarian cancer: in-vitro characterization.

Parenteral administration of recombinant interferon-α-2b (rINF-α-2b) at a dose of 50×10 IU once a week for 8 weeks is recommended for ovarian cancer. However, short half-life, small therapeutic index and proteolytic degradation cause fluctuations in plasma level and pose barriers in the development of a clinically viable dosage form. Therefore, in the present investigation, fluorescein isothiocynate-tagged rINF-α-2b was loaded into stearic acid (*rINF-α-2b-SMs), pectin (*rINF-α-2b-PMs) and gelatin (*rINF-α-2b-GMs) microspheres. Parameters such as particle size, ζ potential, encapsulation efficiency and in-vitro release were studied to follow the optimization process. The formulation, *rINF-α-2b-GMs of particle size 8.3±2.1 µm with an encapsulation efficiency of 76.0±7.4%, offered 97.4% of *rINF-α-2b release at 288 h. Thus, negatively charged extended-release formulation *rINF-α-2b-GMs was then tethered with a gradient concentration (5-20 mg/ml) of a cationic arginine-rich protein stabilizer, protamine sulphate (Pt). The nanoformulation, *rINF-α-2b-Pt-GMs-15 superimposed with 15 mg/ml of Pt, released 95.0% of *rINF-α-2b at 336 h and was designated as the optimized formulation. The optimized formulation also conserved the primary and secondary structure of *rINF-α-2b as analysed by gel electrophoresis and circular dichroism. Moreover, in-vitro cytotoxicity analysis of SKOV3 cells of the optimized nanoformulation reported significantly (one-way analysis of variance test, P<0.05) lower IC50 (414.3 IU/ml) compared with *rINF-α-2b-GMs (514.3 IU/ml) and pure rINF-α-2b (628.6 IU/ml) at 72 h by offering a prolonged cytotoxic effect. Therefore, *rINF-α-2b-Pt-GMs-15, a promising nanomedicine, warrants further in-depth in-vivo study to scale up the technology for clinical translation.

Development and standardization of Indian Alcohol Photo Stimuli (IAPS) for cue-reactivity paradigms in patients with alcohol use disorder.

Background: The availability of appropriate alcohol-related stimuli is a crucial concern for the evaluation and treatment of patients with alcohol dependence syndrome. The study aimed to standardize alcohol-related images with cultural relevance to the Indian setting. Methods: We produced an extensive database of 203 pictures, the Indian Alcohol Photo Stimuli (IAPS), portraying different categories and types of alcoholic beverages, after removing the confounding effects of low-level stimulus parameters (e.g. brightness and blurriness). Thirty patients with alcohol dependence syndrome, currently abstinent, rated each image on visual analog scale (VAS) ranging from 0 (no craving) to 10 (extreme), to determine how typical the stimuli served as craving-relevant stimuli. Results: The mean VAS scores across beverages (ordered from highest to lowest) were whiskey >rum >beer >wine >vodka. Repeated-measures analysis of variance (ANOVA) showed a significant difference in mean VAS scores across beverages (F = 2.93, df = 2.9/86.3, P = 0.039, Greenhouse-Geisser corrected); the effect size for the difference was small (ηp2 = 0.092). A post hoc Bonferroni shows significantly higher VAS scores with whiskey compared with vodka (P = 0.029), whereas the scores were similar across other beverages. A two-way repeated-measures ANOVA for interaction between type of alcoholic beverages and activity was not significant (F = 2.67, df = 2.6/76.6, P = 0.061, Greenhouse-Geisser corrected). Conclusions: We created a standardized alcohol-related image database for studying cue-reactivity paradigms in individuals with alcohol use disorder (AUD). Further research is needed to validate the impact of image features on cue reactivity.

A Critical Review on the Long-Term COVID-19 Impacts on Patients With Diabetes.

BACKGROUND: The world is currently grappling with the potentially life-threatening coronavirus disease 2019 (COVID-19), marking it as the most severe health crisis in the modern era. COVID-19 has led to a pandemic, with the World Health Organization (WHO) predicting that individuals with diabetes are at a higher risk of contracting the virus compared to the general population. This review aims to provide a practical summary of the long-term impacts of COVID-19 on patients with diabetes. Specifically, it focuses on the effects of SARS-CoV-2 on different types of diabetic patients, the associated mortality rate, the underlying mechanisms, related complications, and the role of vitamin D and zinc in therapeutic and preventive approaches. METHODS: Relevant literature was identified through searches on PubMed, Web of Science, and Science Direct in English, up to April 2023. RESULTS: COVID-19 can lead to distressing symptoms and pose a significant challenge for individuals living with diabetes. Older individuals and those with pre-existing conditions such as diabetes, coronary illness, and asthma are more susceptible to COVID-19 infection. Managing COVID-19 in individuals with diabetes presents challenges, as it not only complicates the fight against the infection but also potentially prolongs the recovery time. Moreover, the virus may thrive in individuals with high blood glucose levels. Various therapeutic approaches, including antidiabetic drugs, are available to help prevent COVID-19 in diabetic patients. CONCLUSIONS: Diabetes increases the morbidity and mortality risk for patients with COVID-19. Efforts are globally underway to explore therapeutic interventions aimed at reducing the impact of diabetes on COVID-19.

Port Site Obstructed Hernia in a Morbidly Obese Patient: A Case Report.

Indications for laparoscopic surgeries are increasing in the current era in view of the advantages they offer in terms of less perioperative morbidities, early mobilization, and better cosmesis. These benefits are perceived even more in obese women. However, there are special challenges in this population, associated with their body habitus, poor visibility, and perioperative anesthesia risks. Difficulty in port closure is one such problem encountered in these women causing inadequate rectus suturing and leading to port site hernia. We report a case of a 59-year-old morbidly obese lady who underwent a total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection for carcinoma endometrium. The intraoperative course was uneventful. In the postoperative period, she developed acute obstruction due to port site herniation of the small bowel, which was not suspected till postoperative day five. This was due to an inaccurate assessment of her abdomen because of her body habitus. A CT scan was done in view of the non-resolving obstruction, which revealed herniation of a small bowel loop through the umbilical port. Immediate correction was resorted to under local anesthesia. Rectus sheath closure was done in the same sitting. The patient had a quick recovery after that and was discharged three days later. Rectus sheath closure should be done for all ports 10 mm or greater in diameter. There should be a low threshold to get cross-sectional imaging in postoperative obese women with non-resolving gastrointestinal symptoms.

Drug Repurposing Against Novel Therapeutic Targets in Plasmodium falciparum for Malaria: The computational perspective.

Malaria remains one of the most challenging tropical diseases. Since malaria cases are reportedly alarming in terms of infections and mortality, urgent attention is needed for addressing the issues of drug resistance in falciparum malaria. High throughput screening methods have paved the way for rapid identification of anti-malarial. Furthermore, drug repurposing helps in shortening the time required for drug safety approvals. Hence, the discovery of new antimalarials by drug repurposing is a promising approach for combating the disease. This article summarizes the recent computational approaches used for identifying novel antimalarials by using drug target interaction tools followed by pharmacokinetic studies.

Mechanistic insights into immunopathogenesis of murine cerebral malaria: Cues from "young" C57BL/6J and BALB/c mice.

Cerebral malaria (CM), a major cause of mortality in children <5 years, presents disparity in pathophysiological features and poor prognosis compared to adults. Adult C57BL/6J mice infected with Plasmodium berghei ANKA (PbA) are widely used to understand CM pathogenesis compared to relatively less prone BALB/c mice; however, age and immune status of the host also influence disease sequelae and cerebral manifestations. Murine models of CM known so far do not project complete disease spectrum of pediatric CM. The present study was designed to dissect and differentiate CM immunopathogenesis in "young" BALB/c and C57BL/6J mice infected with PbA, in search of a competent mouse model mimicking pediatric CM. Multipronged approach including the analysis of blood-brain barrier (BBB) permeability and parasite infiltration, histopathology, nitric oxide levels, and pro/anti-inflammatory (TNF-α, IFN-γ, IL-4, and IL-10) cytokine expression were compared in the cortices of both young BALB/c and C57BL/6J mice. The results illustrate severe course of infection and typical CM like histopathological alterations including monocytic plugging in PbA-infected "young" BALB/c compared to C57BL/6J mice. The decreased expression of tight junction proteins (ZO-1 and Claudin-3) and Evan's blue extravasation was also more evident in BALB/c mice indicating a more permeable BBB. The increased cortical expression of TNF-α, IFN-γ, IL-4, IL-10, iNOS, eNOS, nNOS, and associated activation of brain resident cells in cortices of BALB/c with progressive parasitaemia depicts the cumulative involvement of host immune responses and parasite accumulation in progression of CM. Thus, the incongruity of cytokine balance resulted in worsening of disease manifestation in "young" BALB/c similar to pediatric CM.

Concepts on Smart Nano-Based Drug Delivery System.

Nanomedicine is a branch of healthcare, which has many clinical applications. Nanoscale science has to presume an attractive slot for the research in drug delivery as nanocarriers either through active or passive targeting approaches to cell-specific drug delivery. Liposomes, solid-lipid nanoparticles, dendrimers, polymeric nanoparticles, mesoporous silica nanoparticles, inorganic nanoparticles, nanotubes, quantum dots, and nanofibers are nanocarriers that are proven too smart a nano-based drug delivery system. The nanoparticulate system shows high stability, high specificity, high efficacy, and liability to form different dosages, used through different routes, as well as the ability to deliver hydrophobic as well as hydrophilic drugs. These nanoparticulate systems are showing wider applications to cure the disease through nanomedicines and biomedical applications viz. chemical and biological sensors, information storage systems, magneto-optic, optical devices, and fiber-optic systems. In this review article, the author describes various smart nano-based drug delivery systems along with their endocytic pathways used for the uptake of nanoparticles.

Emotional Threat Perception and Its Association with Neurocognition in Social Anxiety Disorder.

Background: The negative appraisal of emotional stimuli is a feature of social anxiety disorder (SAD). People with SAD demonstrate deficits in neurocognitive performance while performing tasks of attention. However, the relationship between attentional control, working memory, and threat perception in SAD has not been studied well. The present study aimed to identify patterns of threat perception in relation to performance on attention and visuospatial working memory tasks in individuals with SAD. Methods: Subjects with SAD (n = 27) and a healthy comparative (HC) group (n = 26) completed tasks of sustained and focused attention, visuospatial working memory, computerized emotion identification, and pictorial emotional Stroop. Results: The SAD group had decreased performance in the domains of sustained (P = 0.001) and focused attention (P = 0.04). They also had an enhanced threat perception as demonstrated by greater reaction time to anger (P = 0.03), lower emotion recognition accuracy (P = 0.05), and higher over-identification of the threat to neutral and nonthreatening faces. However, the Stroop effect was not demonstrated across the groups. No group difference was seen in the performance on the visuospatial working memory tasks. Lower focused attention was significantly correlated with higher emotional threat perception (ETP; P = 0.001) in the SAD group. Conclusion: People with SAD have greater deficits in attention processing and ETP. The attention deficits were associated with enhanced ETP in social anxiety. The link between threat perception and cognitive functions would aid in a better understanding of SAD and in planning appropriate intervention.

Ganga river water quality assessment using combined approaches: physico-chemical parameters and cyanobacterial toxicity detection with special reference to microcystins and molecular characterization of microcystin synthetase (mcy) genes carrying cyanobacteria.

Water quality assessment relies mostly on physico-chemical-based characterization; however, eutrophication and climate change advocate the abundance of toxic microcystins (MCs) producing cyanobacteria as emerging bio-indicator. In the present study, a spatial-temporal analysis was carried out at ten sampling sites of Prayagraj and Varanasi during June 2017 and March 2018 to determine the Ganga River water quality using physico-chemical parameters, cyanobacteria diversity, detection of MCs producing strains and MC-LR equivalence. Coliform bacteria, COD, NO3-N, and phosphate are the significant contaminated parameters favoring the growth of putative MCs producing cyanobacteria. National Sanitation Foundation WQI (NSFWQI) indicates water quality, either bad or medium category at sampling points. The morphological analysis confirms the occurrence of diverse cyanobacterial genera such as Microcystis, Anabaena, Oscillatoria, and Phormidium. PCR amplification affirmed the presence of toxic microcystin (mcy) genes in uncultured cyanobacteria at all the sampling sites. The concentration of MC-LR equivalence in water samples by protein phosphatase 1 inhibition assay (PPIA) and high-performance liquid chromatography (HPLC) methods was observed in the range of 23.4-172 ng/L and 13.2-97.5 ng/L respectively which is lower than the harmful exposure limit by World Health Organization (WHO). Ganga isolate 1 was identified as Microcystis based on partial 16S rDNA sequence and its toxicity was confirmed due to presence of mcy genes and MCs production potential. These findings suggest the presence of MCs producers as new emerging parameter to monitor water quality index and identification up to species level will be valuable for restoration strategies of river Ganga.

A Conceptual Analysis of Solid Self-emulsifying Drug Delivery System and its Associate Patents for the Treatment of Cancer.

BACKGROUND: About two-third of new drugs reveal low solubility in water due to which it becomes difficult for formulation scientists to develop oral solid dosage forms with a pharmaceutically acceptable range of therapeutic activity. In such cases, S-SMEEDS are the best carriers used universally for the delivery of hydrophobic drugs. SEDDS are also used but due to their limitations, SSMEDDS are used widely. These are the isotropic mixtures of oils, co-solvents, and surfactants. SSMEDDS are physically stable, easy to manufacture, easy to fill in gelatin capsules as well as improve the drug bioavailability by releasing the drug in the emulsion form into the gastrointestinal tract and enable smooth absorption of the drug through the intestinal lymphatic pathway. METHODS: We conducted a literature search related to our review, also employing the peer-reviewed research, and provided a conceptual framework. Standard tools were used for drawing the figures of the paper, and various search engines were used for literature exploration. In this review article, the author has discussed the importance of S-SMEDDS, selection criteria for excipients, pseudo-ternary diagram, mechanism of action of S-SMEDDS, solidification techniques used for S-SMEDDS, Characterization of SEDDS and S-SMEDDS including Stability Evaluation of both and future prospects have been concluded through recent findings on S-SMEDDS in Cancer as well as a neoteric patent on S-SMEDDS. RESULTS: Many research papers have been discussed in this review article, from which it was found that the ternary phase diagram is the most crucial part for developing the SMEDDS. From the various research findings, it was found that the excipient selection is the essential step which decides the strong therapeutic effect of the formulation. The significant outcome related to solid-SMEDDS is the less the globule size, the higher would be the bioavailability. The method in which adsorption of a solid carrier takes place is most widely used for the preparation of solid-SMEDDS. After reviewing many patents, it was observed that the solid-SMEDDS have a strong potential for targeting and treating different types of cancer due to their properties to enhance permeation and increase bioavailability. CONCLUSION: S-SMEEDS are more acceptable pharmaceutically as compared to SEDDS due to their various advantages over SEDDS, such as stability issue is prevalent with SEDDS. A number of patent researchers have formulated S-SMEDDS of poorly soluble drugs and found S-SMEDDS as prospective for the delivery of hydrophobic drugs in the treatment of cancer. S-SMEEDS are increasingly grabbing attention, and the patentability on S-SMEDDS is unavoidable, which proves that S-SMEEDS are widely accepted carriers. These are used universally for the delivery of hydrophilic drugs and anticancer drugs as they release the drug to the gastrointestinal tract and enhance the systemic absorption.

Thought Disorder on Object Sorting Test Is Associated with Executive Dysfunction in Schizophrenia.

BACKGROUND: Thought disorder is considered to be central to the core disturbances in schizophrenia and was described by Goldstein as aberrant "concept formation." Executive dysfunction is another core deficit in schizophrenia. With a greater emphasis on psychopathology in nosological systems, the classical thought disorder receives less prominence. The present study aimed to understand the association between classical thought disorder (aberrant concept formation and concrete abstraction) and executive dysfunction. METHODS: Thirty patients with schizophrenia and thirty healthy subjects, matched on age, gender, education, and socioeconomic status, were screened using MINI 5.0, following which they were assessed on object sorting test (OST) and selected tests for executive functions (EFs). RESULTS: Individuals with schizophrenia were found to have significantly decreased performance on all domains of EFs and OST. Total peculiar scores on OST were significantly associated with mental speed, focused attention, and divided attention. Total impoverished scores on OST was significantly associated with focused attention, sustained attention, planning, set shifting, perseveration, and concept formation. CONCLUSION: Several correlations, among performance on OST and neuropsychological tests, suggest that patterns of responses on OST can point to underlying executive dysfunction. Both thought disorder and executive dysfunction mirror similar constructs. This similarity represents a conceptual bridge between the classical and contemporary descriptions of the core deficits in schizophrenia.

Analytical study of the psychosocial impact of malocclusion and maxillofacial deformity in patients undergoing orthodontic treatment.

Patients whose with facial appearance involves dental anomalies and malocclusion face an increased prevalence of various psychosocial problems such as a high level of social anxiety, social avoidance, and low quality of life. This study investigates the patients with craniofacial anomalies and their psychological adjustment concerning the facial and dental appearance. It also evaluates the expectations of this patient group from the orthodontic treatment. Two steps were done in this study. In the first step, translation and validation of the Derriford Appearance Scale (DAS59), The Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ), and Patient Expectation from the Orthodontic Treatment (PEOTQ) questionnaires into Maithili were done, and then the main study was conducted using these valid questionnaires. This was a cross-sectional study conducted on the patients with congenital craniofacial anomalies visiting the orthodontics department of Patna Dental College and Hospital, Patna (Bihar). All the patients received the Maithili DAS, Maithili PIDAQ and Patients' Expectation from the orthodontic treatment questionnaires. The Maithili version of DAS59, PIDAQ and PEOTQ were developed with outstanding reliability and validity. A significant difference between PIDAQ (p<0.001) and DAS59 scores (p<0.001) was found. In females, the total PIDAQ score was significantly higher as compared to males, but there was no association of DAS scores with gender. Place of residence showed no association with PIDAQ and DAS59 scores in patients. Patients and controls had significant differences between various items, and a comparison was made in terms of expectation from the orthodontic treatment. Altered facial and dental appearance in patients with craniofacial anomalies showed a significant psychological impact.

Prefrontal Cortex Transcranial Direct Current Stimulation Treatment in Alcohol Dependence Syndrome (PreCoTTA): Study Protocol for a Double- blind Randomized Sham-controlled Trial.

BACKGROUND: Alcohol dependence is a significant public health problem, contributing to the global health burden. Due to its immense socio-economic burden, various psychosocial, psychological, and pharmacological approaches have attempted to alter the behaviour of the patient misusing or abusing alcohol, but their efficacy is modest at best. Therefore, there is a search for newer treatment approaches, including non-invasive brain stimulation in the management of alcohol dependence. We plan to study the efficacy of Prefrontal Cortex Transcranial direct current stimulation Treatment in Alcohol dependence syndrome (PreCoTTA). METHODS: Two hundred twenty-five male patients with alcohol dependence syndrome will be randomized into the three study arms (2 active, left dorsolateral prefrontal cortex and left orbitofrontal cortex, and 1 sham) to receive a total of 14 tDCS sessions (10 continuous and 4 booster sessions). Data will be collected from these sessions at five different time points on clinical, neuropsychological and biochemical parameters. In addition, 225 healthy age and education matched controls will be administered the neuropsychological test battery at baseline for comparison with the patient group. DISCUSSION: The proposed study aims to explore the use of non-invasive brain stimulation; tDCS as a treatment alternative. We also aim to overcome the methodological gaps of limited sample sizes, fewer tDCS intervention sessions, lack of long-term follow-ups to measure the sustainability of gains, and lack of comprehensive measures to track changes in functioning and abstinence after tDCS intervention. The main outcomes include clinical (reduction in cue-induced craving, time to first drink, and QFI); neuropsychological (risk-taking, impulsivity, and other neuropsychological domains), and biochemical markers (BDNF, leptin and adiponectin). The findings of the study will have translational value as they may help to improve the clinician's ability to effectively manage craving in patients with alcohol dependence syndrome. Furthermore, we will have a better understanding of the neuropsychological and biochemical effects of non-invasive brain stimulation techniques which are of interest in the comprehensive treatment of addiction disorders. TRIAL REGISTRATION: The study has been registered with the Clinical Trials Registry-India (CTRI/ 2020/09/027582) on September 03rd 2020.

Multidisciplinary management of ovarian germ cell tumours-a single institutional study from India.

BACKGROUND: Ovarian germ cell tumours constitute a heterogeneous group of neoplasm with malignant potential being seen in 5% of cases. There is limited data on treatment outcomes of patients with malignant ovarian germ cell tumours (MOGCT). Here, we present our hospital audit of patients with MOGCT. MATERIAL AND METHODS: This is a retrospective data review of patients with MOGCT treated between May 2011 and December 2019. Patients were treated with staging laparotomy and adjuvant chemotherapy, wherever applicable. Surveillance was allowed for those at low risk for recurrence. Clinicopathologic features and treatment details were recorded, and survival analysis was performed. RESULTS: Sixty-five patients with a median age of 25 years (range: 11-52 years) were treated during the study period. The most common histology was immature teratoma in 35.3% of cases. International Federation of Gynecology and Obstetrics stage IC was the most common stage of presentation (47%). Surveillance was advised for 12.3% of cases. Systemic therapy was given in 51 (78%) patients. At a median follow-up of 46 months (range: 1-109 months), the median progression-free survival (PFS) was not reached. Five-year PFS was 79.3% (95% CI: 65.8-88). The most common toxicity was febrile neutropenia (22%) among those who received systemic therapy. CONCLUSION: Immature teratoma was the most common histology in our series. The majority presented in the early stage. MOGCT is a highly curable disease with surgery and systemic therapy.

Clinical and Laboratory Characteristics of Patients with Peritoneal Tuberculosis Mimicking Advanced Ovarian Cancer.

Objectives Peritoneal tuberculosis can mimic advanced abdominal malignancy. We describe clinical and laboratory characteristics in a series of female patients with peritoneal tuberculosis who were referred to a tertiary cancer center with a diagnosis of suspected advanced ovarian/primary peritoneal cancer. Materials and Methods Details of clinical features, laboratory results including serum tumor markers, radiological findings, and ascitic fluid evaluation were retrospectively collected from hospital records for patients diagnosed to have peritoneal tuberculosis and reported descriptively. Statistical Analysis Descriptive statistics was performed using SPSS Statistics for Windows software, version 20.0 (SPSS, Chicago, Illinois). Results Between January 2009 and December 2017, 120 patients of peritoneal tuberculosis with a median age 41 years (range, 15-79 years) were identified. Of these 112 (93.3%; 95% CI 88.9-97.8%) patients had ascites and 63 (52.5%; 95% CI 43.6-61.4%) had adnexal mass at presentation. Mean serum cancer antigen 125 (CA-125) level was 666.9 (range, 38-18,554) U/mL. Ascitic fluid was negative for malignant cells in all patients and lymphocyte rich exudate was seen in 103 (91.9%; 86.9-97.0%) patients. Ascitic fluid adenosine deaminase (ADA) level was more than 40 U/L in 107 (95.5%; 95% CI 91.7-99.4%). Ascitic fluid Ziel-Neelsen staining was positive in 4/62 (6.5%; 95% CI 0.3-12.6%) patients while ascitic fluid culture examination for mycobacterium tuberculosis was positive in 7/59 (11.9%; 95% CI 3.6-20.1%) patients. The diagnosis of tuberculosis was based on image-guided biopsy in 44 (36.7%) patients, surgical biopsy in 8 (6.7%) patients, and a combination of clinicoradiological and laboratory features in 68 (56.7%) patients. All patients received standard antitubercular treatment. Conclusions The study results suggest that peritoneal tuberculosis has clinical, radiological, and serological profile which may mimic advanced ovarian/primary peritoneal cancer. Peritoneal tuberculosis should be considered in the differential diagnosis of advanced abdominal malignancy.