Understanding the cross-talk between human microbiota and gastrointestinal cancer for developing potential diagnostic and prognostic biomarkers.

The interaction between gut microbes and gastrointestinal (GI) tract carcinogenesis has always attracted researchers' attention to identify therapeutic targets or potential prognostic biomarkers. Various studies have suggested that the microbiota do show inflammation and immune dysregulation, which led to carcinogenesis in GI tract. In this review, we have focused on the role of microbes present in the gut, intestine, or faeces in GI tract cancers, including esophageal cancer, gastric cancer, and colorectal cancer. Herein, we have discussed the importance of the microbes and their metabolites, which could serve as diagnostic biomarkers for cancer detection, especially in the early stage, and prognostic markers. To maximize the effect of the treatment strategies, an accurate evaluation of the prognosis is imperative for clinicians. There is a vast difference in the microbiota profiles within a population and across the populations depending upon age, diet, lifestyle, genetic makeup, use of antibiotics, and environmental factors. Therefore, the diagnostic efficiency of the microbial markers needs to be further validated. A deeper understanding of the GI cancer and the host microbiota is needed to acquire pivotal information about disease status.

A Pilot Study on COVID-19 Positive Subjects: An Excerpt of Post-Infection-Pro-Diabetic Disposition & Related Consequences in Correlation to Hepato-Pancreatic Bio-Markers, Pro-Inflammatory Cytokines and Other Risk Factors.

COVID-19, a global pandemic that led to increased morbidity and mortality worldwide since its outcome at the end of the year 2019. A newly discovered variant of severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) was the arbitrator for spreading the syndrome by droplet transmission causing multi-organ failure in many occasions. A post-infection-pro-diabetic disposition was found evident in this study with the persistence of hepato-pancreatic aberrations in respect of reference range of tissue specific bio-markers in hospital admitted COVID-19 cases. The results of this study show that hyperglycemia is a risk factor in precipitating disease oriented complications to the patients with COVID-19 disease. A post-infection follow- up on glycemic-index and related complexities is a vital need to the COVID-19 infected convalescent subjects. Implementation of guidelines on social measure and awareness of anti-viral interventions may be the only way to prevent COVID-19 transmission.

A review upon medicinal perspective and designing rationale of DPP-4 inhibitors.

Type 2 Diabetes Mellitus (T2DM) is one of the highly prevalence disorder and increasing day by day worldwidely. T2DM is a metabolic disorder, which is characterized by deficiency in insulin or resistance to insulin and thus increases the glucose levels in the blood. Various approaches are there to treat diabetes but still there is no cure for this disease. DPP-4 inhibitor is a privileged target in the field of drug discovery and provides various opportunities in exploring this target for development of molecules as antidiabetic agents. DPP-4 acts by inhibiting the incretin action and thus decreases the level of blood glucose by imparting minimal side effects. Sitagliptin, vildagliptin, linagliptin etc. are the different DPP-4 based drugs approved throughout the world for the treatment of diabetes mellitus. Cyanopyrrolidines, triazolopiperazine amide, pyrrolidines are basic core nucleus present in various DPP-4 inhibitors and has potential effects. In the past few years, researchers had applied various approaches to synthesize potent DPP-4 inhibitors as antidiabetic agent without side effects like weight gain, cardiovascular risks, retinopathy etc. This review will also emphasize the recent strategies and rationale utilized by researchers for the development of DPP-4 inhibitors. This review also reveals about the various other approaches like molecular modelling, ligand based drug designing, high throughput screening etc. are used by the various research group for the development of potential DPP-4 inhibitors.

Role of Chest X-Ray in Coronavirus Disease and Correlation of Radiological Features with Clinical Outcomes in Indian Patients.

Recent literature has reported that radiological features of coronavirus disease (COVID-19) patients are influenced by computed tomography. This study aimed to assess the characteristic chest X-ray features of COVID-19 and correlate them with clinical outcomes of patients. This retrospective study included 120 COVID-19 patients. Baseline chest X-rays and serial chest X-rays were reviewed. A severity index in the form of maximum radiological assessment of lung edema (RALE) score was calculated for each lung, and scores of both the lungs were summed to obtain a final score. The mean ± standard deviation (SD) and frequency (%) were determined, and an unpaired t test, Spearman's rank correlation coefficient, and logistic regression analyses were performed for statistical analyses. Among 120 COVID-19 patients, 74 (61.67%) and 46 (38.33%) were males and females, respectively; 64 patients (53.33%) had ground-glass opacities (GGO), 55 (45.83%) had consolidation, and 38 (31.67%) had reticular-nodular opacities, with lower zone distribution (50%) and peripheral distribution (41.67%). Baseline chest X-ray showed a sensitivity of 63.3% in diagnosing typical findings of SARS-CoV-2 pneumonia. The maximum RALE score was 2.13 ± 1.9 in hospitalized patients and 0.57 ± 0.77 in discharged patients (p value <0.0001). Spearman's rank correlation coefficient between maximum RALE score and clinical outcome parameters was as follows: age, 0.721 (p value <0.00001); >10 days of hospital stay, 0.5478 (p value <0.05); ≤10 days of hospital stay, 0.5384 (p value <0.0001); discharged patients, 0.5433 (p value <0.0001); and death, 0.6182 (p value = 0.0568). The logistic regression analysis revealed that maximum RALE scores (0.0932 [0.024-0.367]), (10.730 [2.727-42.206]), (1.258 [0.990-1.598]), and (0.794 [0.625-1.009]) predicted discharge, death, >10 days of hospital stay, and ≤10 days of hospital stay, respectively. The study findings suggested that the RALE score can quantify the extent of COVID-19 and can predict the prognosis of patients.

Quantitative rise in intraocular pressure in patients undergoing robotic surgery in steep Trendelenburg position: A prospective observational study.

BACKGROUND AND AIMS: Raised intraocular pressure (IOP) is one of the known causes of anterior ischemic optic neuropathy. In the case of robotic urological-gynecological surgeries, patient is kept in steep Trendelenburg supine-lithotomy position. Aim of this study was to observe the quantitative rise in IOP in steep Trendelenburg position (>45°) in robotic-assisted prostatectomy and hysterectomy. MATERIAL AND METHODS: After institutional ethical clearance and written informed consent, 100 patients undergoing robotic surgeries in steep Trendelenburg position were recruited for the study. IOP was measured at different time intervals in steep Trendelenburg position using Schiotz tonometer: Post intubation (T1), post pneumoperitoneum (T2), post steep Trendelenburg (T3), and rest readings were taken 30 min apart. T9 was taken 10 min after patient is made supine and parallel to the ground. Mean arterial pressure (MAP), positive inspiratory pressure (PIP), and end-tidal carbon dioxide (EtCO2) values were recorded at different time points. Descriptive analysis, linear regression analysis, and Freidman's nonparametric tests were used to analyze the results. RESULTS: Ninety-five patients were included for statistical analysis as five patients were excluded due to intraoperative interventions leading to alteration of results. Mean IOP at T1 was 19.181/18.462 mmHg in L/R eye. A gradual rise in IOP was observed with every time point while patient was in steep Trendelenburg position which reverts back to near normal values once the patient is changed to normal position 21.419/20.671: Left/right eye in mm of Hg. Uni and multiple regression analysis showed insignificant P value, thus no correlation between MAP, PIP, and EtCO2 with IOP. CONCLUSION: Steep Trendelenburg position for prolong duration leads to significant rise in intraocular pressure.

Functional analysis of vocal folds by transcutaneous laryngeal ultrasonography in patients undergoing thyroidectomy.

BACKGROUND: Transcutaneous laryngeal ultrasound (TCLUS) can assess Vocal folds (VF) by subjectively identifying mobility or objectively by calculating vocal fold displacement velocity (VFDV). Optimal diagnostic approach (subjective assessment, VFDV estimation or a combination of both) is unresolved; hence, we conducted this prospective study in patients undergoing thyroidectomy. METHOD: Two anaesthetists performed TCLUS pre- and post-operatively for functional assessment of 200 VFs on 100 patients. Their findings were compared with pre-operative flexible laryngoscope (FL) performed by surgeons and with post-operative C-Mac video laryngoscope (C-Mac VL) by another independent anaesthetist. Correlation between FL and TCLUS findings and inter-rater agreement between TCLUS findings of both anaesthetists was analysed. Decision curve analysis (DCA) was performed to compare clinical benefit of hoarseness, subjective VF movement, VFDV, and combined assessment for detecting disabled VFs. RESULTS: We found good correlation between VF mobility on TCLUS and FL (Spearman's r = 0.93, P < 0.0001) as well as C-Mac VL (Spearman's r = 0.83, P < 0.0001) with excellent inter-rater agreement between both anaesthetists. DCA showed combined assessment to have marginally higher clinical benefit than other diagnostic approaches at intermediate threshold probabilities while its benefit was similar to subjective evaluation at higher threshold probabilities. CONCLUSION: Provided achievement of optimal acoustic window, TCLUS can reliably assess disabled VFs with FL reserved for their confirmation or doubtful cases. Subjective assessment of VF mobility should suffice in most cases with additional VFDV estimation reserved pre-operatively for situations with higher risk of VFs disability, and post-operatively when subjective VF assessment findings are discordant from pre-operative status.

Regulatory approval process for advanced dressings in India: an overview of rules.

OBJECTIVE: There is a high rate of death due to burns and wound infections in India. Innovators and manufacturers of wound and burn dressings need to keep themselves abreast of the most current rules governing medical devices. The concept of advanced dressings is emerging in India. However, local manufacturing is hindered by an absence of clear regulatory guidelines. The lack of advanced wound and burn dressings on the market critically affects patient survival rates, while imports from other countries make dressings unaffordable and beyond the reach of most patients. This article presents the details of an approval procedure for advanced dressings and provides manufacturers, innovators and investors with a better understanding of the classification rules, import, export and marketing approval processes. We also discus the reasons for high levels of imports and costs, as well as suggestions on how to address this. METHOD: A critical analysis was conducted of 54 research and review articles, including regulatory guidelines to control the marketing of wound and burn care dressings recommended by international regulatory agencies. CONCLUSION: India is highly dependent on imports of advanced dressings. Due to lack of clear, quality regulatory guidelines, innovators and manufacturers are facing issues while showcasing their product in the Indian market. Thus development of clear quality regulatory guidelines is crucial. Therefore, this article may guide and encourage manufacturers to develop advanced dressings in India.

HCN-producing Pseudomonas protegens CHA0 affects intraradical viability of Rhizophagus irregularis in Sorghum vulgare roots.

Arbuscular mycorrhizal fungi (AMF) and plant growth-promoting rhizobacteria inhabit the plant rhizosphere. Both functional groups can influence plant community structures, and interactions between them can vary from being synergistic to antagonistic. HCN-producing Pseudomonas protegens CHA0 is a plant growth-promoting rhizobacterium. P. protegens CHA0 has been shown to weakly attach to AMF hyphae. Here, we analyze the effect of P. protegens CHA0 on the viability of intraradical AMF hyphae. Using pot experiments, we have grown mycorrhizal and nonmycorrhizal Sorghum vulgare var. M35 with P. protegens CHA0 or HCN- mutant P. protegens CHA77, which did not produce HCN. Mycorrhizal and nonmycorrhizal Sorghum grown without CHA0 or CHA77 served as the control. While metabolically active AMF was not detected in mycorrhizal plants grown with HCN+ CHA0, the percentage of root colonization of metabolically active AMF in plants grown with HCN- CHA77 was lower than in the control. Root phosphorus was highest in mycorrhizal plants grown with HCN+ CHA0, but root Fe was higher in plants grown with the bacterial strains. Our results indicate that HCN-producing P. protegens can affect the viability of intraradical AMF.

Ring graft technique for microvascular decompression.

INTRODUCTION: Various nerve compression syndromes, such as trigeminal neuralgia (TN), glossopharyngeal neuralgia (GN), and hemifacial spasm (HFS), are caused by compression of the concerned nerve by the adjacent vessel. Patients who do not respond to medical management are usually treated by "microvascular decompression (MVD) of the nerve." Teflon patch graft is the most commonly used material for MVD. This graft has been used in various shapes like a patch, in the shredded form, or as a sling. This is done to prevent recurrence because of graft failure. We used a teflon ring graft to perform a successful MVD in 10 patients. MATERIAL AND METHODS: Out of 10 cases, 6 cases were of TN, 2 of HFS, 1 of GN, and 1 case was of cochleovestibular nerve compression syndrome (CNCS). After MVD, every patient underwent a follow up assessment for 5 years. RESULTS: There was no major postoperative complication, except in the patient with CNCS who suffered from a temporary episode of facial palsy. All cases were symptom free at a follow-up duration of equal to or more than 5 years. CONCLUSION: Ring teflon graft may be used as an alternative as well as a safe method to perform MVD and has a good success rate.

Portal Annular Pancreas: A Rare and Overlooked Anomaly.

BACKGROUND: Portal annular pancreas is a rare pancreatic developmental anomaly which is often overlooked at imaging, and often diagnosed retrospectively when it is detected incidentally at the time of surgery. Although the anomaly itself is asymptomatic, it becomes important in cases where pancreatic resection/anastomosis is planned, because of varying ductal anatomy, risk of ductal injury and increased risk of postoperative pancreatic fistula formation. CASE REPORT: We present imaging findings in a case of portal annular pancreas in a 45-year-old male patient. CONCLUSIONS: Portal annular pancreas is a rare and often neglected pancreatic anomaly due to a lack of awareness of this entity. With the advent of MDCT and MRI, accurate preoperative diagnosis of this condition is possible.

Magnetic Resonance Imaging (MRI) Depiction of Robert's Uterus: A Rare Müllerian Duct Anomaly Presenting with Cyclical Pain in Young Menstruating Woman.

BACKGROUND: Robert's uterus is a very rare müllerian duct anomaly which is characterised by septate uterus with obstruction of a one-sided cavity and formation of hematometra. Therefore, patients present with cyclical abdominal pain during menstruation along with normal menstrual flow. CASE REPORT: We present magnetic resonance imaging (MRI) findings in a case of Robert's uterus in a young woman. CONCLUSIONS: Robert's uterus is a very rare anomaly which can be very well characterized by magnetic resonance imaging (MRI). MRI can also show any associated hematometra and endometriomas complicating this condition and aid in the institution of appropriate management in such cases.

Studies on Aspirin Crystals Generated by a Modified Vapor Diffusion Method.

The objectives of the current investigation were (1) to study the influence of selected two different non-solvents (diethylether and dichloromethane) on the drug crystal formation of a model drug, aspirin (ASP-I) by the modified vapor diffusion method and (2) to characterize and compare the generated crystals (ASP-II and ASP-III) using different analytical techniques with that of unprocessed ASP-I. When compared to the classical vapor diffusion method which consumes about 15 days to generate drug crystals, the modified method needs only 12 h to get the same. Fourier transform-infrared spectroscopy (FT-IR) reveals that the internal structures of ASP-II and ASP-III crystals were identical when compared with ASP-I. Although the drug crystals showed a close similarity in X-ray diffraction patterns, the difference in the relative intensities of some of the diffraction peaks (especially at 2θ values of around 7.7 and 15.5) could be attributed to the crystal habit or crystal size modification. Similarly, the differential scanning calorimetry (DSC) study speculates that only the crystal habit modifications might occur but without involving any change in internal structure of the generated drug polymorphic form I. This is further substantiated from the scanning electron microscopy (SEM) pictures that indicated the formation of platy shape for the ASP-II crystals and needle shape for the ASP-III crystals. In addition, the observed slow dissolution of ASP crystals should indicate polymorph form I formation. Thus, the modified vapor diffusion method could routinely be used to screen and legally secure all possible forms of other drug entities too.

Intraoperative lung ultrasound: A clinicodynamic perspective.

In the era of evidence-based medicine, ultrasonography has emerged as an important and indispensable tool in clinical practice in various specialties including critical care. Lung ultrasound (LUS) has a wide potential in various surgical and clinical situations for timely and easy detection of an impending crisis such as pulmonary edema, endobronchial tube migration, pneumothorax, atelectasis, pleural effusion, and various other causes of desaturation before it clinically ensues to critical level. Although ultrasonography is frequently used in nerve blocks, airway handling, and vascular access, LUS for routine intraoperative monitoring and in crisis management still necessitates recognition. After reviewing the various articles regarding the use of LUS in critical care, we found, that LUS can be used in various intraoperative circumstances similar to Intensive Care Unit with some limitations. Except for few attempts in the intraoperative detection of pneumothorax, LUS is hardly used but has wider perspective for routine and crisis management in real-time. If anesthesiologists add LUS in their routine monitoring armamentarium, it can assist to move a step ahead in the dynamic management of critically ill and high-risk patients.

Chronic lymphocytic leukemia cells in a lymph node microenvironment depict molecular signature associated with an aggressive disease.

Chronic lymphocytic leukemia (CLL) cells survive longer in vivo than in vitro, suggesting that the tissue microenvironment provides prosurvival signals to tumor cells. Primary and secondary lymphoid tissues are involved in the pathogenesis of CLL, and the role of these tissue microenvironments has not been explored completely. To elucidate host-tumor interactions, we performed gene expression profiling (GEP) of purified CLL cells from peripheral blood (PB; n = 20), bone marrow (BM; n = 18), and lymph node (LN; n = 15) and validated key pathway genes by real-time polymerase chain reaction, immunohistochemistry and/or TCL1 trans-genic mice. Gene signatures representing several pathways critical for survival and activation of B cells were altered in CLL cells from different tissue compartments. Molecules associated with the B-cell receptor (BCR), B cell-activating factor/a proliferation-inducing ligand (BAFF/APRIL), nuclear factor (NF)-κB pathway and immune suppression signature were enriched in LN-CLL, suggesting LNs as the primary site for tumor growth. Immune suppression genes may help LN-CLL cells to modulate antigen-presenting and T-cell behavior to suppress antitumor activity. PB CLL cells overexpressed chemokine receptors, and their cognate ligands were enriched in LN and BM, suggesting that a chemokine gradient instructs B cells to migrate toward LN or BM. Of several chemokine ligands, the expression of CCL3 was associated with poor prognostic factors. The BM gene signature was enriched with antiapoptotic, cytoskeleton and adhesion molecules. Interestingly, PB cells from lymphadenopathy patients shared GEP with LN cells. In Eµ-TCL1 transgenic mice (the mouse model of the disease), a high percentage of leukemic cells from the lymphoid compartment express key BCR and NF-κB molecules. Together, our findings demonstrate that the lymphoid microenvironment promotes survival, proliferation and progression of CLL cells via chronic activation of BCR, BAFF/APRIL and NF-κB activation while suppressing the immune response.

A rare manifestation of cysticercosis infestation.

There are many causes of urticaria, which may vary from infections to malignancy. Among the infections, infestations by cysticercosis (larval stage of the tapeworm called Taenia solium) is an important cause. The present report is of forty four years old female who presented with urticaria and swelling on face. The swelling was later diagnosed as cysticercosis by noninvasive ultrasonography. The urticaria subsided after the treatment of cysticercosis. We report this case for rarity of its presentation.

Molecular Docking, Pharmacophore Modeling, and ADMET Prediction of Novel Heterocyclic Leads as Glucokinase Activators.

BACKGROUND: A pivotal impetus has driven the development of numerous small molecules aiming to improve therapeutic strategies for type 2 diabetes. Glucokinase (GK) activation has been offered a new realm of therapeutic antidiabetic activity with novel heter-ocyclic derivatives. In the context of antidiabetic drug design, GK is an interesting and newly validated target. A key enzyme needed for blood glucose homeostasis is Glucokinase, which is dysfunctional in individuals with type 2 diabetes. Heterocyclic derivatives are utilized in this innovative approach to activate GK enzymes as medicinal agents that will significantly improve type 2 diabetes management. OBJECTIVE: To address type 2 diabetes, as well as minimize unwanted side effects, this research endeavor aimed to develop activators of glucokinase. METHODS: A rigorous scrutiny was conducted of the Maybridge online repository, which houses a formidable collection of 53,000 lead compounds. A collection of 125 compounds that contain the thiazolidinedione core was selected from this extensive collection. The struc-tures were generated using ChemDraw 2D, stabilized conformation with ChemBioDraw Ul-tra, and docked using Auto Dock Vina 1.5.6 in this methodology. In addition, log P was pre-dicted online using the Swiss ADME algorithm. The PKCSM software was used to predict the toxicity of the leading compounds. RESULTS: The highest binding affinity was found for AS72 and AS108 to GK receptors. GI absorption and excretion of these compounds were efficient due to Lipinski's Rule of Five compliance. When compared with the standard drugs Dorzagliatin (GKA) and MRK (co-crys-tallized ligand), these substances demonstrated a notable lack of AMES toxicity, skin sensiti-zation, and hepatotoxicity. CONCLUSION: In recent studies, lead molecules that possess enhanced pharmacokinetic profiles, increased binding affinity, and lower toxicity were developed to act as glucokinase activators.

Comparative Analysis of US Guidelines for the Management of Cutaneous Squamous Cell and Basal Cell Carcinoma.

Background: This study presents a comparative analysis of recently published guidelines to manage cutaneous squamous cell carcinoma (cSCC) and cutaneous basal cell carcinoma (cBCC) within the United States (US). Methods: A PubMed database search was performed for the time period between June 1, 2016, and December 1, 2022. A comprehensive comparison was performed in the following clinical interest areas: staging and risk stratification, management of primary tumor and regional nodes with curative intent, and palliative treatment. Results: Guidelines from 3 organizations were analyzed: the American Academy of Dermatology (AAD), the National Comprehensive Cancer Network (NCCN), and the American Society for Radiation Oncology (ASTRO). The guidelines used different methodologies to grade evidence, making comparison difficult. There was agreement that surgery is the preferred treatment for curative cBCC and cSCC. For patients ineligible for surgery, there was a consensus to recommend definitive radiation. AAD and NCCN recommended consideration of other topical modalities in selected low-risk cBCC. Postoperative radiation therapy (PORT) was uniformly recommended in patients with positive margins that could not be cleared with surgery and in patients with nerve invasion. The definition and extent of nerve invasion varied. All guidelines recommended surgery as the primary treatment in patients with lymph node metastases in a curative setting. The criteria used for PORT varied; NCCN and ASTRO used lymph node size, number of nodes, and extracapsular extension for recommending PORT. Both NCCN and ASTRO recommend consideration of systemic treatment along with PORT in patients with extracapsular extension. Conclusion: US guidelines provide contemporary and complementary information on the management of cBCC and cSCC. There are opportunities for research, particularly in the areas of staging, indications for adjuvant treatment in curative settings, extent of nerve invasion and prognosis, and the role of systemic treatments in curative and palliative settings.