Association of Red Cell Distribution Width and Mean Platelet Volume With Disease Activity in Rheumatoid Arthritis Patients.

BACKGROUND: The inner layer of the synovial joints is the primary target of rheumatoid arthritis, or RA, a chronic systemic inflammatory disorder that is linked to increasing disability, early mortality, and economic hardships. The objective is to determine the association of red cell distribution width (RDW) and mean platelet volume (MPV) with disease activity in RA. MATERIAL AND METHODS: A retrospective study was conducted between July 2021 and January 2022 in the outpatient rheumatology clinics at Gulab Devi Teaching Hospital. In this study, 100 consecutive participants with a diagnosis of RA fulfilling the ACR/EULAR 2010 classification criteria were enrolled. Patient's records were reviewed for age, gender, length of illness, smoking status, treatment history, current treatment regimen, concomitant medications, rheumatoid factor (RF), anti-cyclic citrulline peptide (anti-CCP) antibodies, and extra-articular manifestations. Laboratory investigations were reviewed for complete blood count including RDW and MPV, ESR, CRP, liver, and renal functions. Disease activity score DAS 28-ESR was used to quantify disease activity. To determine the relationship between different parameters and the RDW and MPV, linear regression research was conducted. RESULTS: According to the DAS28 score, 12% of patients were in remission, 9% had low, 34% had moderate, and 45% had high disease activity. DAS28 score was 5.01±1.72 (2.45-9.32) and RDW was 16.18±4.42. There was a strong positive correlation (r = 0.653) of RDW with the DAS28 score and it was statistically significant (p<0.001). MPV was 11.30±2.09 fL. There was a moderately positive correlation (r = 0.366) of MPV with the DAS28 score and it was statistically significant (p<0.001). CONCLUSION: Conclusively, both RDW and MPV are positively related to disease activity in patients with RA. These can be used as a simple tool for assessing disease activity and guiding the treatment.

Comparison of Predictive Models for Prevention of Missed Endoscopy Appointments- failure of a Predictive Model to Outperform Overbooking Model.

BACKGROUND: Patient late cancelation and nonattendance for endoscopy appointments is an ongoing problem affecting the productivity and wait times of endoscopy units. Previous research evaluated a model for predictive overbooking and had promising results. STUDY: All endoscopy visits at an outpatient endoscopy unit during 4 nonconsecutive months were included in the data analysis. Patients who did not attend their appointment, or canceled with 48 hours of their appointment were considered nonattendees. Demographic, health, and prior visit behavior data was collected and the groups compared. RESULTS: 1780 patients attended 2331 visits in the study period. Comparing the attendee versus non-attendees, there were significant differences in mean age, prior absenteeism, prior cancelations, and total number of hospital visits. No significant differences were seen between groups in winter versus non-winter months, the day of the week, sex distribution, type of procedure booked, or whether the referral was from specialist clinic or direct to procedure. The visit cancelation proportion (calculated excluding current visit) was substantially higher in the absentee group ( P <0.0001). A predictive model was developed and compared to current booking as well as a straight overbooking of 7%. Both overbooking models performed better than the current practice, but the predictive overbooking model did not outperform straight overbooking. CONCLUSIONS: Developing an endoscopy unit specific predictive model may not be more beneficial than straight overbooking as calculated by missed appointment percentage.

Synthesis and Structural Activity Relationship Study of Ursolic Acid Derivatives as Antitubercular Agent.

OBJECTIVE: The chemical transformation of ursolic acid (UA) into novel C-3 aryl ester derivatives and in vitro and silico assessment of their antitubercular potential. BACKGROUND: UA is a natural pentacyclic triterpenoid with many pharmacological properties. Semisynthetic UA analogs have demonstrated enhanced anticancer, antimalarial, and antifilarial properties in our previous studies. METHOD: The C-30 carboxylic group of previously isolated UA was protected, and various C-3 aryl ester derivatives were semi-synthesized. The agar dilution method was used to evaluate the in vitro antitubercular efficacy of Mycobacterium tuberculosis (Mtb) H37Ra. In silico docking studies of the active derivative were carried out against Mtb targets, catalase peroxidase (PDB: 1SJ2), dihydrofolate reductase (PDB: 4M2X), enoyl-ACP reductase (PDB: 4TRO), and cytochrome bc1 oxidase (PDB: 7E1V). RESULTS: The derivative 3-O-(2-amino,3-methyl benzoic acid)-ethyl ursolate (UA-1H) was the most active among the eight derivatives (MIC1 2.5 µg/mL) against Mtb H37Ra. Also, UA-1H demonstrated significant binding affinity in the range of 10.8-11.4 kcal/mol against the antiTb target proteins, which was far better than the positive control Isoniazid, Ethambutol, and co-crystallized ligand (HEM). Moreover, the predicted hit UA-1H showed no inhibition of Cytochrome P450 2D6 (CYP2D6), suggesting its potential for favorable metabolism in Phase I clinical studies. CONCLUSION: The ursolic acid derivative UA-1H possesses significant in vitro antitubercular potential with favorable in silico pharmacokinetics. Hence, further in vivo assessments are suggested for UA-1H for its possible development into a secure and efficient antitubercular drug.

Long COVID syndrome: psychological and sexual dysfunction among survivors of COVID-19 infection.

Background: To explore the neuropsychiatric symptoms, sleep disturbances, and sexual dysfunction in patients with long COVID syndrome, which can help in building better follow-up strategies for coronavirus disease 2019 (COVID-19) survivors. Material and methods: A cross-sectional research was undertaken at the premises of a psychiatry unit at a tertiary care unit in Karachi, Pakistan, between August 2022 and April 2023. All individuals aged 18 years or older, who had a history of contracting COVID-19 infection in the last 12 months presented to the department of Psychiatry with neuropsychiatric symptoms were recruited. Using a predefined questionnaire, data was collected from the participants. A linear logistic regression was used to find the impact of age, sex, hospitalization, and duration of home isolation on the likelihood of persistent neuropsychiatric symptoms or sexual dysfunction. Results: A total of 457 patients were included. It was found that individuals were less likely to experience neuropsychiatric symptoms as age increased (OR=0.968, 95% CI: 0.949-0.986, P=0.001). Females were 4.8 times more likely to experience neuropsychiatric symptoms than males, and the association was extremely significant (OR=4.851, 95% CI: 3.085-7.626, P<0.0001). An increase in age raised the odds of having sleep disturbances among the survivors by 2.7 times (OR=2.672, 95% CI: 2.654-2.684, P<0.0001). The odds of having sleep disturbances were three times more likely in female participants as compared to male participants (OR=3.00, 95% CI: 1.771-5.094, P<0.0001). Conclusion: The majority of the COVID-19 survivors are presenting with persistent neuropsychiatric and sexual symptoms in our setting. Therefore, it is necessary to maintain proper follow-up with the survivors of COVID-19 and counsel the patients to inform the family physician if these symptoms persist for longer than a month. Increasing such practices of regular follow-ups with COVID-19 survivors can help in detecting early neuropsychiatric and sexual changes.

Multiomic Analysis Identifies a High-Risk Metabolic and TME Depleted Signature that Predicts Early Clinical Failure in DLBCL.

PURPOSE: 60-70% of newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients avoid events within 24 months of diagnosis (EFS24) and the remainder have poor outcomes. Recent genetic and molecular classification of DLBCL has advanced our knowledge of disease biology, yet were not designed to predict early events and guide anticipatory selection of novel therapies. To address this unmet need, we used an integrative multiomic approach to identify a signature at diagnosis that will identify DLBCL at high risk of early clinical failure. PATIENTS AND METHODS: Tumor biopsies from 444 newly diagnosed DLBCL were analyzed by WES and RNAseq. A combination of weighted gene correlation network analysis and differential gene expression analysis followed by integration with clinical and genomic data was used to identify a multiomic signature associated with high risk of early clinical failure. RESULTS: Current DLBCL classifiers are unable to discriminate cases who fail EFS24. We identified a high risk RNA signature that had a hazard ratio (HR, 18.46 [95% CI 6.51-52.31] P < .001) in a univariate model, which did not attenuate after adjustment for age, IPI and COO (HR, 20.8 [95% CI, 7.14-61.09] P < .001). Further analysis revealed the signature was associated with metabolic reprogramming and a depleted immune microenvironment. Finally, WES data was integrated into the signature and we found that inclusion of ARID1A mutations resulted in identification of 45% of cases with an early clinical failure which was validated in external DLBCL cohorts. CONCLUSION: This novel and integrative approach is the first to identify a signature at diagnosis that will identify DLBCL at high risk for early clinical failure and may have significant implications for design of therapeutic options.

Accessing medical care for infertility: a study of women in Mexico.

Objective: To investigate barriers in accessing care for infertility in Mexico, because little is known about this issue for low and middle-income countries, which comprise 80% of the world's population. Design: Cross-sectional analysis. Setting: Mexcian Teachers' Cohort. Patients: A total of 115,315 female public school teachers from 12 states in Mexico. Interventions: None. Main Outcome Measures: The participants were asked detailed questions about their demographics, lifestyle characteristics, access to the health care system, and infertility history via a self-reported questionnaire. Log-binomial models, adjusted a priori for potential confounding factors, were used to estimate the prevalence ratios (PRs) and 95% confidence intervals ( CIs) of accessing medical care for infertility among women reporting a history of infertility. Results: A total of 19,580 (17%) participants reported a history of infertility. Of those who experienced infertility, 12,470 (63.7%) reported seeking medical care for infertility, among whom 8,467 (67.9%) reported undergoing fertility treatments. Among women who reported a history of infertility, women who taught in a rural school (PR, 0.95; 95% CI, 0.92-0.97), spoke an indigenous language (PR, 0.88; 95% CI, 0.84-0.92), or had less than a university degree (PR, 0.93; 95% CI, 0.90-0.97) were less likely to access medical care for fertility. Women who had ever had a mammogram (PR, 1.07; 95% CI, 1.05-1.10), had a pap smear in the past year (PR, 1.08; 95% CI, 1.06-1.10), or who had used private health care regularly or in times of illness were more likely to access medical care for fertility. Conclusions: The usage of infertility care varied by demographic, lifestyle, and access characteristics, including speaking an indigenous language, teaching in a rural school, and having a private health care provider.

Synthesis of amide derivatives of 3-aryl-3H-benzopyrans as osteogenic agent concomitant with anticancer activity.

The present study reports a series of 3-aryl-3H-benzopyran-based amide derivatives as osteogenic agents concomitant with anticancer activity. Six target compounds viz 22e, 22f, 23i, and 24b-d showed good osteogenic activity at 1 pM and 100 pM concentrations. One of the potential molecules, 24b, effectively induced ALP activity and mRNA expression of osteogenic marker genes at 1 pM and bone mineralization at 100 pM concentrations. These molecules also presented significant growth inhibition of osteosarcoma (MG63) and estrogen-dependent and -independent (MCF-7 and MDA-MB-231) breast cancer cells. The most active compound, 24b, inhibited the growth of all the cancer cells within the IC50 10.45-12.66 µM. The mechanistic studies about 24b showed that 24b induced apoptosis via activation of the Caspase-3 enzyme and inhibited cancer cell migration. In silico molecular docking performed for 24b revealed its interaction with estrogen receptor-ß (ER-ß) preferentially.

Pre-existing conditions associated with post-acute sequelae of COVID-19.

Post-acute sequelae of COVID-19 (PASC) are conditions that occur or remain at least 28 days after SARS-CoV-2 infection. While some risk factors for PASC have been identified, little is known about pre-existing conditions that render one susceptible to developing PASC. Data from participants (n = 1224) in a longitudinal COVID-19 cohort study in Arizona were used to investigate comorbid conditions associated with PASC. After adjustment of the models for age, BMI, gender, race, and smoking, the following pre-existing conditions were statistically significantly associated with the development of PASC: asthma (OR = 1.54; 95% CI = 1.10-2.15); chronic constipation (OR = 4.29; 95% CI = 1.15-16.00); reflux (OR = 1.54; 95% CI = 1.01-2.34); rheumatoid arthritis (OR = 3.69; 95%CI = 1.15-11.82); seasonal allergies (OR = 1.56; 95% CI = 1.22-1.98); and depression/anxiety (OR = 1.72; 95% CI = 1.17-2.52). When grouping conditions together, statistically significant associations with PASC were observed for respiratory (OR = 1.47; 95% CI = 1.06-2.14); gastrointestinal (OR = 1.62; 95% CI = 1.16-2.26), and autoimmune conditions (OR = 4.38; 95% CI = 1.59-12.06). After adjustment for severity of acute SARS-CoV-2 infection and depression/anxiety, seasonal allergies (OR = 1.48; 95% CI 1.15-1.91) and autoimmune disease (OR = 3.78; 95% CI - 1.31-10.91) remained significantly associated with risk for PASC. These findings indicate that numerous pre-existing conditions may be associated with an increased risk for the development of PASC. Patients with these conditions should consider taking extra steps to avoid infection.

The impact of gendered experiences on female medical students' specialty choice: A systematic review.

BACKGROUND: Women make up 50% of American medical school graduates, yet are not equally represented in the vast spectrum of medical specialties. Many fields within medicine remain male dominated. This systematic review will explore social factors that affect female medical students' specialty choice. HYPOTHESIS: Gendered experiences influence the specialty choice of female medical students, resulting in their concentration in a specific cohort of specialties. METHODS: Studies were gathered by searching MEDLINE/Pubmed and EBSCOhost for sociological factors that impact female medical students' specialty choice. RESULTS: 34 articles were selected for this systematic review. Factors that contribute to gender segregation within medical specialties include gender discrimination, socialization, lifestyle considerations, negative perceptions of male-dominated medical specialties and lack of female role models. CONCLUSION: This systematic review supported the hypothesis that gendered experiences impact women's medical specialty choice, and thus result in their concentration in specialties such as family medicine, pediatrics and obstetrics and gynecology.

Analysis of a pre-2017 follicular variant papillary thyroid carcinoma cohort reclassified as noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP): an 11-year retrospective single institution experience.

INTRODUCTION: Noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP), represents a distinct class of thyroid neoplasms with very low risk of adverse outcome and a set of strict histologic criteria. Introduction of NIFTP as a non-cancer has had an appreciable decrease in risk of malignancy and body of literature on this entity continues to grow. In this study, we reviewed clinical, fine-needle aspiration cytology (FNAC), imaging, and molecular findings of histologically proven NIFTPs at our institution. MATERIALS AND METHODS: Thyroid resections during an 11-year period, with histologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC), were retrospectively reviewed to identify NIFTP. Ultrasonographic appearance, FNA findings, and molecular findings were also reviewed. RESULTS: Of 244 cases of FVPTC identified, 74 (30%) cases were reclassified as NIFTP. Mean tumor size was 2.5 cm. Of 33 patients with lymph node dissection, none had lymph node metastases. On imaging, 36 NIFTP (49%) showed vascularity, 25 (33%) were isoechoic to hypoechoic, there were calcifications in 14 cases (19%), and 7 cases (9%) showed a hypoechoic rim. Bethesda III/IV was the most common interpretation rendered on FNAC (31%). Seven cases had NRAS mutations and 1 case had BRAF V600E mutation. The remaining cases were either negative for BRAF V600E or had no identifiable molecular alterations. CONCLUSIONS: A significant percentage of tumors previously diagnosed as FVPTC were reclassified as NIFTP. This tumor cannot be reliably diagnosed preoperatively on FNAC, shows no characteristic features on ultrasound and has low suspicion of malignancy. BRAF V600E mutations are infrequent in NIFTP.

Genotoxic hazard and oxidative stress induced by wastewater irrigated soil with special reference to pesticides and heavy metal pollution.

Due to enhancement of industrial growth and urbanization, soil contamination is increasing prominently. Therefore, it is important to examine possible adverse effects of industrial waste. Soil samples were might to be polluted with several heavy-metals and pesticides. Gas chromatographic results showed occurrence of high-level of organochlorine and organophosphate pesticides in studied soil samples. Genotoxicity of soil extracts was assessed using environmental-risk assessment models. Soil samples were extracted in hexane and dichloromethane solvents and were evaluated for genotoxic potential by prokaryotic (Ames test, plasmid nicking assay and E. coli K-12 DNA repair defective mutants) and eukaryotic (Allium cepa root chromosomal aberration and Vigna radiata seed-germination test) bioassays. Strain TA98 was found the most susceptible among soil extracts. The mutagenicity of hexane soil extract from wastewater irrigation was found to be higher than that of DCM samples in terms of mutagenic index, mutagenic potential, and induction factor for Ames strains. The damage in DNA repair defective mutants of hexane extracts were found higher compared to DCM extracts at dose of 20 µl/ml of culture. Survival in polA, lexA and recA mutants were 39%, 47% and 55% while treated with hexane extract. Allium cepa test, mitotic index was decreased in dose-dependent way and various kinds of chromosomal aberrations were found. Vigna radiata seeds germination and other parameters were also affected when treated with wastewater irrigated (WWI) soil. Oxidative stress in V. radiata roots were also showed under CLS microscope. Genotoxicity of WWI soil extract was also confirmed by plasmid nicking test. Our study provides possible explanation for the assessment of potential health and environmental hazards of the industrial region.

Severe Airway Edema Following Calcium Hydroxylapatite (CaHA) Injection Augmentation.

This case study presents an abnormal complication after routine injection augmentation using calcium hydroxylapatite (CaHA) vocal fold filler in-office on a 73-year-old female. The patient presented initially with severe dysphonia, hypophonia, and a past surgical history of total thyroidectomy, bilateral neck dissection, and a right lateral neck dissection for history of metastatic papillary thyroid carcinoma. She also had a past medical history of hypothyroidism. Post-injection of CaHA, the patient developed severe laryngeal edema, limited vocal cord mobility, obliteration of the pyriform, and a significantly reduced airway aperture requiring intensive care monitoring. Although uncommon, injectable fillers can result in complications which can be severe. Careful technique, the volume of injectate, and hypersensitivity should be considered in reducing complications following injection augmentation. There are multiple injection techniques to consider. The most direct approach is with direct laryngoscopy to allow for visualization of glottic incompetence. A smaller slotted laryngoscope can be considered for vocal fold injection as an alternative and without endotracheal intubation. Although these techniques allow for injection, real-time assessment of vocal fold closure is done in an awake patient. Therefore, laryngeal injection can be considered via percutaneous, per-oral, and trans-nasal approaches.

Laryngotracheal Recurrent Papillomatosis: A Case Study and Survey of Surgical and Systemic Management.

This case report presents a 72-year-old man with longstanding recurrent respiratory papillomatosis (RRP). He has undergone multiple procedures for the condition, including an apparent urgent surgical airway followed by tracheoplasty repair. Modern management of complicated RRP should include both local debulking and systemic approaches. Systemic bevacizumab (Avastin) has shown some initial success as an effective treatment option, in addition to other medications such as pembrolizumab. Other future care strategies may include an HPV vaccination and other adjuvants; vaccination has been reported to have the possibility of drastically reducing the incidence of RRP.

Evidence-based recommendations for induction and maintenance treatment of newly diagnosed transplant-ineligible multiple myeloma patients.

There is increasing evidence regarding the role of various maintenance therapy (MT) strategies after initial induction to treat newly diagnosed transplant-ineligible patients with MM. We reviewed the literature on available regimens for patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM). Lenalidomide (R)-based regimens are still the front-line therapy, but there is an increasing use of bortezomib-based regimens. The MT regimen is mainly based on the initial induction regimen. MT has shown survival benefits compared with patients without maintenance therapy. The most common adverse effects of MT include anemia, neutropenia, thrombocytopenia, infections, and peripheral neuropathy. In conclusion, induction followed by maintenance based on lenalidomide, bortezomib, ixazomib, or daratumumab-based regimens has shown promising results. Therefore, it is essential to conduct more clinical trials to better understand the role of MT in the treatment of NDMM patients who are not candidates for autologous stem cell transplantation.

Synthesis, Molecular Docking, and 2D-QSAR Modeling of Quinoxaline Derivatives as Potent Anticancer Agents against Triple-negative Breast Cancer.

BACKGROUND: Breast carcinomas aka triple-negative breast cancers (TNBC) are one of the most complex and aggressive forms of cancers in females. Recently, studies have shown that these carcinomas are resistant to hormone-targeted therapies, which makes it a priority to search for effective and potential anticancer drugs. The present study aimed to synthesize and develop the 2Dquantitative structural activity relationship model (QSAR) of quinoxaline derivatives as a potential anticancer agent. METHODS: Quinoxaline derivatives were designed and synthesized (8a-8i and 9a-9d) and the 2DQSAR model against TNBC was developed using VLife MDS v4.4. The anticancer activity was investigated against the TNBC MDA-MB-231 cell line using an MTT cytotoxicity assay. Molecular docking studies along with the estimation of ADMET parameters were done using Discovery Studio. The most potent compound was docked against the ß-tubulin protein target (PDB: 4O2B), using the Autodock Vina v0.8 program. RESULTS: Eleven derivatives of quinoxaline were designed and synthesized (8a-8i and 9a-9d) and a 2D-QSAR model was developed against the TNBC MDA-MB231 cell line. The regression coefficient values for the training set were (r2) 0.78 and (q2) 0.71. Further, external test set regression (pred_r2) was 0.68. Five molecular descriptors viz., energy dispersive (Epsilon3), protein-coding gene (T_T_C_6), molecular force field (MMFF_6), most hydrophobic hydrophilic distance (XA), and Zcomp Dipole were identified. After ADMET, the best analog 8a showed the best activity against the TNBC cell line. The best-predicted hit '8a' was found to bind within the active site of the ß- tubulin protein target. CONCLUSION: The newly synthesized quinoxaline compounds could serve as potent leads for the development of novel anti-cancer agents against TNBC.

Profiles of Whole Blood Transfusion Recipients at a Teaching Hospital in Lahore, Pakistan.

Background Blood transfusion plays a vital role in medical practice. Evaluation of blood utilization in a blood bank is a crucial step in good transfusion practice. It is the inception towards assessing the present and future demands for blood and also avoiding unnecessary transfusions. Methods Retrospective analysis of one-year data, available in the blood bank of Gulab Devi Hospital Lahore, was done to study blood transfusion practice. Issue registers were accessed to retrieve the required information such as gender, age, blood group, pre-transfusion Hemoglobin level, ward, clinical diagnosis, and indication for the transfusion. The data was analyzed using SPSS version 20 software. Frequency and percentages were used to summarize categorical demographics and clinical variables. Results A total of 1181 units were requested from the hospital during our study period. Majority of the requests were for the female patients (69%) of the reproductive age group (21 to 30 years). Blood group B positive was most frequent in our study population. Maximum requests were from reproductive health departments (39.9%). Surgery was the major diagnostic category to require blood transfusions (31.8%). Elective surgery constituted the major indication requiring blood transfusion at our hospital (41.3%). Conclusion Blood utilization patterns vary significantly within geographical regions, hospital to hospital, and according to clinical practices as well as patients' clinical findings. Moreover, diseases burden, level of organization, and advancement of healthcare facilities in various settings contribute to the significant contrast in blood utilization trends.

Biosynthesis of iron oxide magnetic nanoparticles using clinically isolated Pseudomonas aeruginosa.

Magnetotactic bacteria are microscale complex natural systems that synthesize magnetic nanoparticles through biologically controlled mineralization. Nanoparticles produced by this process are biocompatible due to the presence of surrounding membranes. The mechanism controlling synthesis is cost-effective and is executed by complex genomes (operons). The results are monodispersed magnetic nanoparticles displaying advantages over polydispersed ones synthesized by physical and chemical methods. In this work, we isolated Pseudomonas aeruginosa from clinical samples and demonstrated its ability to biosynthesize magnetic nanoparticles. P. aeruginosa was thrived in a carbon-minimal medium supplemented with iron at low pH. The cells aligned parallel to a magnetic field, confirming their magnetic properties. The magnetic nanoparticles were extracted, purified, and characterized using electron microscopy, magnetometry, dynamic light scattering, and X-ray diffraction. This work represents the first isolation of a magnetotactic bacterium from clinical samples. The aerobic nature of these bacteria allows them to be easily cultured under laboratory conditions, unlike their well-known microaerophilic counterparts. The biosynthesized magnetic nanoparticles can be used in many applications, including magnetic resonance imaging, diagnostics, and therapeutics (i.e., magnetic hyperthermia).

Empagliflozin nanoparticles attenuates type2 diabetes induced cognitive impairment via oxidative stress and inflammatory pathway in high fructose diet induced hyperglycemic mice.

There is snowballing evidence that type 2 diabetes (T2D) predisposes to neuropathophysiological alterations including oxidative stress and triggered inflammatory responses in brain that eventually culminates into cognitive impairment.Accumulating evidences suggest that SGLT2 inhibitor can be a promising intervention for cognitive decline in T2DM. In the present paper, the potential effects of Empagliflozin (EMPA), a SGLT2 inhibitor, against T2D induced cognitive dysfunction have been explored. The effect of EMPA on array of inflammatory mediators including Interleukin-6(IL-6), Interleukin -1ß (IL-1ß), and Tumour necrosis factor-α(TNF-α)), neuronal proteins including glycogen synthase kinase-3ß (GSK- 3ß), Phosphorylated tau (p-tau), amyloid beta (Aß) (1-40, 1-42) and altered oxidative parameters including SOD, catalase, TBARS was determined in the high fructose diet induced hyperglycaemic mice. The obtained results were compared with EMPA nanoparticles (Nps) formulated in our laboratory and found that EMPA Nps significantly showed reduced levels of inflammatory mediators and oxidative stress. Further, decrease in levels of p-tau, Aß (1-40) and Aß (1-42) were also observed with EMPA nanoparticles.Thus, the study has demonstrated that EMPA Nps could be a promising therapy to alleviate the progression of cognitive decline in T2D.

Dawn of a new era of antibody-drug conjugates and bispecific T-cell engagers for treatment of multiple myeloma: a systematic review of literature.

Multiple myeloma (MM) remains an incurable disease with the majority of patients experiencing disease relapse despite response to initial therapy. Antibody-drug conjugates (ADCs) and bispecific T-cell engagers are innovative immunotherapeutic approaches currently in development for the treatment of MM. This systematic review summarizes the efficacy and safety of ADCs and bispecific T-cell engagers in relapsed refractory (RR) MM patients from 2010 to date. Comprehensive literature search was conducted on PubMed, EMBASE, Wiley Cochrane Library, Web of Science, and Clinicaltrials.gov . A total of 13 studies (n = 529) met inclusion eligibility. All studies were prospective in nature investigating ADCs or bispecific T-cell engagers in RR MM; 10 trials were phase 1 and 3 were phase 2. The median age of patients ranged from 24 to 82 years. Among trials with ADC regimens, the overall response (OR) ranged from 34 to 60% and complete response (CR) ranged from 3 to 6%. The most common non-hematologic adverse event (AE) of ADCs was keratopathy, while anemia and thrombocytopenia were the most common hematological AEs. With bispecific T-cell engagers , ORR ranged from 31 to 83%, CR ranged from 7 to 22%, and partial response (PR) ranged from 5 to 16%. The most common non-hematologic AE of bispecific T-cell engagers was cytokine release syndrome (CRS) while the most common hematological AE was neutropenia. Initial data appears to show good clinical activity and tolerable safety profiles, making ADCs and bispecific T-cell engagers promising agents for RRMM. Future studies with newer combinations and a longer follow-up are needed to determine the precise role of these novel therapies in the evolving paradigm of MM treatment.