Oral squamous cell carcinoma is the sixth most common cancer worldwide. Despite the available treatment, the survival rate is poor. The addition of agents to make chemotherapeutics safer and more effective is important. Curcumin is a common Indian spice that has shown anticarcinogenic properties. It has been possible to overcome its poor bio-availability using nanotechnology. We aimed to investigate the adjuvant effect of nanocurcumin (NC ~ 200 nm size) treatment on cetuximab (epidermal growth factor receptor inhibitor) in oral squamous cancer cells (KB 3-1 cell). Cancer cells were cultured and treated for 24 hours with cetuximab and NC, in various doses to find the drugs' half-maximal inhibitory concentration (IC₅₀). Experiments were conducted with a combination dose of both and sensitization treatment with NC before cetuximab with cytotoxicity assessment by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. One-way analysis of variance (ANOVA) was used to compare different treatment groups. We found a concentration-dependent cancer cell death with NC, which was significant compared to cetuximab (p <0.001). The combination treatment group had highly significant cell death (p <0.0001) compared to a single drug, and the NC sensitization caused substantial cell death compared to a single cetuximab treatment (p<0.01). Our study findings indicate the potential chemo-adjuvant effect of NC in oral cancer.

Subclinical hypothyroidism (SCH) and gestational diabetes mellitus (GDM) are common endocrinological abnormalities associated with pregnancy. The presence of a raised anti-thyroperoxidase (anti-TPO) antibody titer increases the risk of progression of subclinical hypothyroidism to overt hypothyroidism. Subclinical hypothyroidism and GDM are known to affect maternal and fetal outcomes adversely. A few studies have shown an increased risk of GDM with autoimmune hypothyroidism. However, data regarding this association between GDM, SCH, and anti-TPO Ab are scarce. This study aimed to find the prevalence of autoimmune subclinical hypothyroidism and its association with GDM in pregnancy. In a cross-sectional study, 382 pregnant women at their first antenatal checkup (ANC) were enrolled in the study. Serum thyroid-stimulating hormone (TSH), free T4 (FT4), anti-TPO Ab, and the 75 g oral glucose tolerance test (OGTT) were evaluated. The results obtained were analyzed in Systat Version 13.2 (SPSS Inc., Chicago, IL). Results showed an SCH prevalence of 37.69% with a raised anti-TPO Ab titer in 49.31% of the diagnosed SCH cases, pointing towards an autoimmune etiology. Our study revealed a GDM prevalence of 12.04%. Out of the 46 GDM cases, 16 were found to have SCH and 3 cases had raised anti-TPO Ab titers. In our study, 27.73% of euthyroid pregnant women had a raised anti-TPO Ab titer. Our study revealed no significant association between GDM, SCH, and raised anti-TPO Ab titer. Anti-TPO antibody subsequently leads to hypothyroxinemia, for which it is necessary that cases with high titer of anti-TPO antibody though euthyroid should be meticulously followed up and screened for to detect development of hypothyroidism or SCH, particularly in future pregnancies. However, GDM prevalence was at par with the national figure, but with no significant association of SCH and a high anti-TPO ab titer was found with GDM in our study. Further studies with a larger cohort may establish a causal association between the two most common endocrinological disorders observed in pregnancy.

Coronavirus disease-19 (COVID-19) patients often deteriorate rapidly based on viral infection-related inflammation and the subsequent cytokine storm. The clinical symptoms were found to be inconsistent with laboratory findings. There is a need to develop biochemical severity score to closely monitor COVID-19 patients. This study was conducted in the department of biochemistry at All India Institute of Medical Sciences (AIIMS) Bhubaneswar in collaboration with the intensive care unit. Laboratory data of 7,395 patients diagnosed with COVID-19 during the first three waves of the pandemic were analyzed. The serum high sensitivity high-sensitivity C-reactive protein (hs-CRP, immuno-turbidity method), lactate dehydrogenase (LDH, modified Wacker et al. method), and liver enzymes (kinetic-UV method) were estimated by fully automated chemistry analyzer. Serum ferritin and interleukin-6 (IL-6) were measured by one-step immunoassay using chemiluminescence technology. Three models were used in logistic regression to check for the predictive potential of biochemical parameters, and a COVID-19 biochemical severity score was calculated using a non-linear regression algorithm. The receiver operating characteristic curve found age, urea, uric acid, CRP, ferritin, IL6, and LDH with the highest odds of predicting ICU admission for COVID-19 patients. COVID-19 biochemical severity scores higher than 0.775 were highly predictive (odds ratio of 5.925) of ICU admission (AUC=0.740, p<0.001) as compared to any other individual parameter. For the validation, 30% of the total dataset was used as testing data (n=2095) with a sensitivity of 68.3%, specificity of 74.5%, and odds ratio of 6.304. Age, urea, uric acid, ferritin, IL6, LDH, and CRP-based predictive probability algorithm calculating COVID-19 severity was found to be highly predictive of ICU admission for COVID-19 patients.

It is of interest to establish clinically valid reference intervals (RIs) for the liver enzymes aspartate transaminase (AST) and Alanine aminotransferase (ALT) using a combination of unsupervised machine learning clustering and robust outlier detection applied to real-world laboratory big data. Four outlier detection methods were each combined with four clustering algorithms to identify homogeneous subgroups and the largest cluster from each combination was used to estimate RIs based on percentile cut-offs. Among the tested combinations, DBSCAN with Tukey’s fences or Local Outlier Factor achieved optimal performance, covering 100% of the validation data. The widest intervals were derived using Local Outlier Factor, while Isolation Forest yielded the narrowest. Ultimately, the study estimated the reference intervals for AST and ALT to be 15–41 U/L and 11–46 U/L, respectively.

Background Studies have shown that aberrant reactions of the immune system play an important role in the pathogenesis of preeclampsia. The immune checkpoint molecules programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) system and the T-regulatory cells (Tregs) system are decisive in the regulation of immune responses and can be the target molecules in preeclampsia. In this study, an attempt has been made to evaluate the soluble PD-L1 (sPD-L1) in the serum of preeclampsia cases and correlate it with Tregs and inflammatory markers to have an insight into the link between these immunomodulatory molecules in the pathogenesis of preeclampsia. Materials and methods Ten normal fertile women, 20 trimester-matched normal pregnancy cases, and 20 preeclampsia cases were enrolled in the study. Serum sPD-L1, transforming growth factor beta 1 (TGF-(31), (31), and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). High-sensitive C-reactive protein (hsCRP) was estimated using a clinical biochemistry autoanalyzer. Tregs were evaluated using flow cytometry. Results and discussion The immune checkpoint molecule PD-L1 inversely correlated with Tregs in preeclampsia cases. Associated inflammation was seen by raised IL-6 and hsCRP. The breakdown of immunological tolerance is mainly caused by the dysregulating the Tregs/Th17 balance, which leads to conditions of autoimmunity and chronic inflammatory disorders. PD-L1 can be the link between this immunological misbalance. Conclusion Our study, showing an increase in sPD-L1 and TGF and a decrease in Tregs with an increase in inflammatory markers like IL-6 and hsCRP levels in preeclampsia, has potential implications for early diagnosis and management of the condition. PD-L1 and Tregs can be target molecules for early management of preeclampsia.

Introduction: Gestational diabetes mellitus (GDM) and hypothyroidism are the most common endocrinological abnormalities associated with pregnancy. The association of gravida with incidence of autoimmune subclinical hypothyroidism (SCH) and GDM in pregnancy has not been studied extensively with availability of very limited data in this context. So, this study was done to find out the association between GDM and autoimmune SCH in pregnancy as per gravida status of the study population. Materials and Methods: 382 antenatal cases, both primi and multigravida, were screened for thyroid dysfunction and GDM in their first ANC coming to a tertiary level health care institution. 75 gm GCT was used for diagnosis of GDM and serum TSH, fT4, and anti-TPO antibody were measured for assessment of thyroid dysfunction. Prevalence of SCH was evaluated taking the ATA 2011 guidelines. Data obtained was also compared with ATA 2017 recommendations. Anti-TPO antibody level more than 60 U/L was considered to be raised value. Observation: The percentage of GDM was higher in autoimmune SCH participants compared to euthyroid cases with raised anti-TPO Ab Titer. GDM, SCH, and raised anti-TPO Ab titer were overall more prevalent in multigravida cases compared to primigravida participants. Conclusion: GDM and SCH with high anti-TPO Ab titer were more prevalent in multigravida participants compared to primigravida cases though not statistically significant. As occurrence of SCH varies with nutritional and geographical factors, hence internal trimester specific range should be calculated and used in practice as recommended by ATA 2017 guidelines.