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We aimed to investigate the potential role of biomarkers of transmethylation, oxidative stress, and mitochondrial dysfunction in children with Autism Spectrum Disorder (ASD) by comparing them with that of typically developing children (TDC) controls. We also tried to correlate them with severity of autism, sensory issues, behavioural comorbidities and developmental quotients 119 with ASD and 52 age and sex matched typically developing children (TDC) controls were enrolled excluding those with chronic-illness or on any antioxidant therapy/multivitamins/anti-epileptic drugs. Median levels of biomarkers - serum homocysteine, cysteine, methionine, urine uric acid-to-creatinine ratio, arterial lactate, serum vitamin E, vitamin B12, folate, Nε-carboxymethyllysine, Nω- carboxymethylarginine (CMA), dityrosine and MTHFR C677T polymorphism were calculated. Children with ASD were further characterised using Childhood Autism Rating Scale-2, Childhood behavioural checklist, child sensory profile 2 caregiver questionnaire, Developmental Profile 3 for any correlation with the various biomarker levels. The median level of serum homocysteine in ASD group was 9 μmol/L(Range, 7- 16μmol/L), which was significantly higher than controls 7 μmol/L(Range, 4- 11μmol/L)(p=0.01). The prevalence of hyper-homocystinemia(>15μmol/L) was 13.4% in ASD as compared to 3.8% in controls with a significant difference(p=0.04). Dityrosine level was higher among ASD children when compared to TDC (9.8 vs 2.2 counts per second(cps), p<0.001). No significant correlation was found between prevalence of hyperhomocysteinemia and severity of autism/DQ/behavioural issues. No significant difference was found between the median levels of other biomarkers. Results support possible role of transmethylation defects and oxidative stress in ASD pathogenesis. Further studies are warranted for a better understanding of ASD pathogenesis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Stromal-epithelial communication is an absolute necessity when it comes to the morphogenesis and pathogenesis of solid tissues, including the prostate and breast. So far, signalling pathways of several growth factors have been investigated. Besides such chemical factors, non-coding RNAs such as miRNAs have recently gained much interest because of their variety and complexity of action. Prostate and breast tissues being highly responsive to steroid hormones such as androgen and estrogen, respectively, it is not surprising that a huge set of available literature critically investigated the interplay between such hormones and miRNAs, especially in carcinogenesis. This review showcases our effort to highlight hormonally-related miRNAs that also somehow perturb the regular stromal-epithelial interactions during carcinogenesis in the prostate and breast. In future, we look forward to exploring how hormonal changes in the tissue microenvironment bring about miRNA-mediated changes in stromal-epithelial interactome in carcinogenesis and cancer progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the risk of acquiring COVID-19 infection in patients who have undergone adeno-tonsillectomy (AT) as compared to their siblings., Methods: In this bidirectional cohort control study, 36 cohorts, younger than 18 y, who underwent AT, and 27 controls (siblings of the enrolled cohorts, younger than 18 y) were recruited. Incidence of COVID-19 was analyzed by symptoms suggestive of COVID-19 infection, COVID-19 testing, and SARS-CoV-2 specific antibody measurement., Results: In the cohort group, the overall COVID-19 positivity rate was 80.5% (n = 29/36) and symptomatic COVID-19 positivity rate was 68.9% (n = 20/29). Among the controls, the overall COVID-19 positivity rate was 44% (n = 12/27) and symptomatic COVID-19 positivity rate was 16% (n = 2/12). The cohorts had 1.8 times higher risk of contracting COVID-19 infection and the relative risk of symptomatic COVID-19 infections as compared to controls was 4.14., Conclusions: This pilot study indicates that adeno-tonsillectomy poses children at a significantly higher risk of COVID-19 infections and likely other viral upper respiratory tract infections., (© 2024. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Current treatment options available for prostate cancer (PCa) patients have many adverse side effects and hence, new alternative therapies need to be explored. Anticancer potential of various phytochemicals derived from Calotropis procera has been studied in many cancers but no study has investigated the effect of leaf extract of C. procera on PCa cells. Hence, we investigated the effect of C. procera leaf extract (CPE) on cellular properties of androgen-independent PC-3 and androgen-sensitive 22Rv1 cells. A hydroalcoholic extract of C. procera was prepared and MTT assay was performed to study the effect of CPE on viability of PCa cells. The effect of CPE on cell division ability, migration capability and reactive oxygen species (ROS) production was studied using colony formation assay, wound-healing assay and 2',7'-dichlorodihydrofluorescein diacetate assay, respectively. Caspase activity assay and LDH assay were performed to study the involvement of apoptosis and necrosis in CPE-mediated cell death. Protein levels of cell cycle, antioxidant, autophagy and apoptosis markers were measured by western blot. The composition of CPE was identified using untargeted LC-MS analysis. Results showed that CPE decreased the viability of both the PCa cells, PC-3 and 22Rv1, in a dose- and time-dependent manner. Also, CPE significantly inhibited the colony-forming ability, migration and endogenous ROS production in both the cell lines. Furthermore, CPE significantly decreased NF-κB protein levels and increased the protein levels of the cell cycle inhibitor p27. A significant increase in expression of autophagy markers was observed in CPE-treated PC-3 cells while autophagy markers were downregulated in 22Rv1 cells after CPE exposure. Hence, it can be concluded that CPE inhibits PCa cell viability possibly by regulating the autophagy pathway and/or altering the ROS levels. Thus, CPE can be explored as a possible alternative therapeutic agent for PCa., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Repeated serological testing tells about the change in the overall infection in a community. This study aimed to evaluate changes in antibody prevalence and kinetics in a closed cohort over six months in different sub-populations in India. The study included 10,000 participants from rural and urban areas in five states and measured SARS-CoV-2 antibodies in serum in three follow-up rounds. The overall seroprevalence increased from 73.9% in round one to 90.7% in round two and 92.9% in round three. Among seropositive rural participants in round one, 98.2% remained positive in round two, and this percentage remained stable in urban and tribal areas in round three. The results showed high antibody prevalence that increased over time and was not different based on area, age group, or sex. Vaccinated individuals had higher antibody prevalence, and nearly all participants had antibody positivity for up to six months., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Misra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Ocular tear film and the ocular surface together represent a dynamic playground of various protective factors against environmental influencers. Surrounding environment and geoclimatic milieu are the pertinent and continuous influencing factors. Prevalence study of Dry eye disease (DED) in various climatic conditions and professions provides an insight into this peculiar aspect of DED and human geography., Methods: This was a hospital based, cross-sectional, comparative, analytical observational study. 1840 young soldiers between 25 and 45 years of age were studied. Divided in five climate groups based on Köppen-Geiger climate classification system the subjects were sub-grouped into professions exposed to known aggravating environmental factors. The ocular surface was examined for signs and symptoms of DED and its prevalence and risk ratio for different climates and professions were calculated., Results: Highest prevalence of DED was found in cold desert climate and among visual display unit (VDU) users. Least prevalence was seen in highland type of climate and among people involved in professional exposed to high temperature. Prevalence of DED based upon the signs and ocular surface disease index (OSDI) was calculated and stratified with risk ratio for climatic conditions and professions., Conclusion: Different climatic conditions and professions had different prevalence of signs, symptoms of OSD and DED which indicated its influence on prevalence of the disease., Competing Interests: The authors have none to declare., (© 2022 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Objectives: Pulmonary congestion is a central feature of heart failure (HF) seen in acute decompensated state as well as in chronic stable disease. The present study sought to determine whether simplified cardiac magnetic resonance imaging (CMR)-derived lung water density (LWD) measurement has prognostic relevance in predicting adverse cardiovascular outcomes in patients with HF and left ventricular ejection fraction (LVEF)<50%., Methods: Eighty consecutive patients referred for CMR with HF and LVEF<50% along with 22 healthy age- and sex-matched controls were prospectively recruited. LWD was the lung-to-liver signal intensity ratio multiplied by 70% (estimated hepatic water density). The primary endpoint was composite of all-cause mortality or HF-related hospitalization within 6 months from CMR., Results: The mean LWD was significantly higher in HF patients compared to healthy controls (19.78 ± 6.1 vs 13.6 ± 2.3; p < 0.001). The mean LWD was significantly different among patients with NYHA class I/II and NYHA class III/IV (17.88 ± 4.8 vs 21.77 ± 1.08; p = 0.004). At 6 months, the primary endpoint was reached in 12 (15%) patients. Patients with "wet lungs" (LWD > 18.1%) had higher incidence of adverse cardiovascular outcomes compared to patients with "dry lungs". LWD was an independent predictor of adverse cardiovascular outcomes in multivariable analysis. At the optimal cut-off of LWD > 23.38%, the sensitivity and specificity were 91.67 and 91.18%, respectively, to predict adverse cardiovascular outcomes., Conclusion: LWD on CMR is independently associated with increased risk of mortality and HF-related hospitalization in HF patients with LVEF<50%., Advances in Knowledge: Non-invasive quantitative estimation of LWD on CMR can improve risk stratification and guide management in HF patients.

Introduction: Surgical complication following esophageal atresia repair is one of the several factors known to influence the final outcomes. Early identification of such complications may help in timely institution of therapeutic measures and translate into improved prognosis., Objective: The objective of this study was to evaluate the role of procalcitonin in early prediction of the adverse events after surgery in patients of esophageal atresia and the temporal relationship with clinical manifestations and other inflammatory biomarkers such as C-reactive protein (CRP)., Materials and Methods: This was a prospective study on consecutive patients of esophageal atresia ( n = 23). Serum procalcitonin and CRP levels were assessed at baseline (prior to surgery) and on postoperative days (POD) 1, 3, 5, 7, and 14. The trends in the biomarker values and temporal relationships of deviation in trend with the clinical and conventional laboratory parameters and patient outcomes were analyzed., Results: Baseline serum procalcitonin was elevated ( n = 23; 1.7 ng/ml: min: 0.07 ng/ml-max: 24.36 ng/ml) in 18/23 (78.3%) patients. Procalcitonin nearly doubled on POD-1 ( n = 22; 3.28 ng/ml: min: 0.64 ng/ml-max: 16.51 ng/ml) followed by a gradual decline. CRP was also elevated on POD-1 (three times the baseline) and depicted a delayed peak at POD-3. POD-1 procalcitonin and CRP levels correlated with survival. POD-1 procalcitonin cutoff at 3.28 ng/ml predicted mortality with a sensitivity and specificity of 100% and 57.9% ( P = 0.05). Serum procalcitonin and CRP were higher for patients who sustained complications, so was the time required for hemodynamic stabilization. Procalcitonin (baseline and POD-5) and CRP (POD-3 and POD-5) values correlated with the clinical course after surgery. Baseline procalcitonin cutoff at 2.91 ng/ml predicted the possibility of a major complication with a sensitivity of 71.4% and a specificity of 93.3%. POD-5 procalcitonin cutoff at 1.38 ng/ml predicted the possibility of a major complication with a sensitivity of 83.3% and a specificity of 93.3%. Patients who sustained major complications depicted a change in serum procalcitonin trend 24-48 h ahead of clinical manifestation of an adverse event., Conclusions: Procalcitonin is a good indicator to identify the adverse events in neonates after surgery for esophageal atresia. The procalcitonin levels in patients who sustained a major complication depicted a reversal in trend 24-48 h of clinical manifestation. POD-1 procalcitonin correlated with survival while the baseline and POD-5 serum procalcitonin predicted the clinical course., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Indian Association of Pediatric Surgeons.)

Background: Several methodological tests are available to detect SARS-CoV-2 antibody. Tests are mostly used in the aid of diagnosis or for serological assessment. No tests are fully confirmatory and have variable level of diagnostic ability. We aimed at assessing agreement with three serological tests: quantitative anti receptor binding domain ELISA (Q-RBD), qualitative ELISA (WANTAI SARS-CoV-2 Ab) and qualitative chemiluminescence assay (CLIA)., Methods: This study was a part of a large population based sero-epidemiological cohort study. Participants aged 1 year or older were included from 25 randomly selected clusters each in Delhi urban (urban resettlement colony of South Delhi district) and Delhi rural (villages in Faridabad district, Haryana). Three type of tests were applied to all the baseline blood samples. Result of the three tests were evaluated by estimating the total agreement and kappa value., Results: Total 3491 blood samples collected from March to September, 2021, out of which 1700 (48.7%) from urban and 1791 (51.3%) from rural. Overall 44.1% of participants were male. The proportion of sero-positivity were 78.1%, 75.2% and 31.8% by Wantai, QRBD and CLIA tests respectively. The total agreement between Wantai and QRBD was 94.5%, 53.1% between Wantai and CLIA, and 56.8% between QRBD and CLIA. The kappa value between these three tests were 0.84 (95% CI 0.80-0.87), 0.22 (95% CI 0.19-0.24) and 0.26 (95% CI 0.23-0.28)., Conclusions: There was strong concordance between Wantai and QRBD test. Agreement between CLIA with other two tests was low. Wantai and QRBD tests measuring the antibody to same S protein can be used with high agreement based on the relevant scenario., (© 2022. The Author(s).)

Background: Estimating seroepidemiolgical prevalence of SARS-CoV-2 antibody is an essential public health strategy. There is insufficient evidence of prevalence among those belonging to young age population in India., Objective: To compare the SARS-CoV-2 seropositivity rate between children and adults in selected sites from India., Materials and Methods: This was a multicentric population-based seroepidemiological study conducted in selected urban and rural areas of five sites selected from four states (Delhi, Odisha, Uttar Pradesh, Tripura) of India. Participants aged ≥1 year were included from different clusters of each area. Total serum antibody against SARS-CoV-2 virus was assessed qualitatively by using a standard enzyme-linked immunosorbent assay (ELISA) kit., Results: Data collection period was from 15 March 2021 to 10 June 2021. Total available data was of 4509 participants, of whom 700 were <18 years of age and 3809 were ≥18 years of age. The site-wise number of available data among those aged 2-17 years was 92, 189, 165, 146 and 108 for the sites of Delhi urban, Delhi rural, Bhubaneswar rural, Gorakhpur rural and Agartala rural area, respectively. The seroprevalence was 55.7% in the <18 years age group and 63.5% in the ≥18 years age group. The prevalence among female children was 58% and among male children was 53%., Conclusion: SARS-CoV-2 seropositivity rate among children was high and comparable to that of the adult population. Hence, it is unlikely that any future third wave by prevailing SARS-CoV-2 variant would disproportionately infect children 2 years or older., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Introduction: The objective of the study was to evaluate the clinical profile and outcome of patients with secondary hemophagocytic lymphohistiocytosis (HLH) in critically ill patients., Materials and Methods: A prospective observational study was conducted where critically ill adult patients presenting with fever and bicytopenia were evaluated according to the HLH-2004 diagnostic criteria for the presence of secondary HLH. The underlying trigger, clinical profile, treatment, and outcome of patients with HLH were analyzed., Results: Of the 76 critically ill patients with fever and bicytopenia, 33 (43%) patients were diagnosed with HLH. The following triggers for HLH were identified: bacterial infections (23%), fungal infections (10%), viral infections (10%), parasitic infections (10%), autoimmune diseases (13%), and malignancy (8%). A total of 78% of the HLH cases received steroids, but the use of steroids was not associated with improvement in mortality., Conclusion: There is a high prevalence of HLH in patients presenting with fever and bicytopenia in critically ill adult patients. Infections were identified as the most common trigger of HLH., How to Cite This Article: Fazal F, Gupta N, Soneja M, Mitra DK, Satpathy G, Panda SK, et al . Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study. Indian J Crit Care Med 2022;26(5):564-567., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2022; The Author(s).)

Epigenetic changes alter the expression of genes at both pre- and post-transcriptional levels without changing their DNA sequence. Accumulating evidence suggests that such changes can modify cellular behavior and characteristics required during development and in response to various extracellular stimuli. Trophoblast cells develop from the outermost trophectoderm layer of the blastocyst and undergo many phenotypic changes as the placenta develops. One such phenotypic change is differentiation of the epithelial natured cytotrophoblasts into the mesenchymal natured extravillous trophoblasts. The extravillous trophoblasts are primarily responsible for invading into the maternal decidua and thus establishing connection with the maternal spiral arteries. Any dysregulation of this process can have adverse effects on the pregnancy outcome. Hence, tight regulation of this epithelial-mesenchymal transition (EMT) is critical for successful pregnancy. This review summarizes the recent research on the epigenetic regulation of the EMT occurring in the trophoblast cells during placental development. The functional significance of chemical modifications of DNA and histone, which regulate transcription, as well as non-coding RNAs, which control gene expression post-transcriptionally, is discussed in relation to trophoblast biology., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Human papillomavirus type 16 (HPV16) plays a major role in the development of cervical cancer. The oncogenic potential of HPV16 is attributed to E6 and E7 oncoproteins. Here, we investigated the relationship between fused toes homolog (FTS) and HPV16 E6 and E7 in cervical cancer cells. HPV16-positive CaSki and SiHa cell lines were used for in vitro studies. FTS silencing was performed using a small interfering RNA (siRNA)-based approach, and western blotting was performed to determine the protein expression of tumor suppressors and cell survival markers. Immunoprecipitation, immunofluorescence, in silico analysis, and immunohistochemistry were performed to determine the interaction between, and intracellular co-localization of, FTS and both the E6 and E7 proteins. Silencing of FTS reduced the expression of the E6 and E7 proteins in cervical cancer cell lines and conversely increased the expression of the tumor suppressor proteins p53 and retinoblastoma protein. However, the primary transcripts of HPV16 E6 and E7 were unaffected by FTS silencing; furthermore, FTS transcription was unaffected by silencing of either E6 or E7, suggesting their interaction occurs post-translationally. Immunofluorescence and immunohistochemistry analysis demonstrated co-localization of FTS with the HPV16 E6 and E7 proteins, while immunoprecipitation results suggested that FTS interacts with both E6 and E7. Furthermore, in silico structural analysis identified putative residues involved in the binding of FTS with E6 and E7. Taken together, these results show that FTS affects both HPV16 E6 and E7 oncogenes in cervical cancer. We propose FTS as a target for the prevention of cervical cancer development and progression., Competing Interests: The authors have declared that no competing interests exist.

Background: Patients with asymptomatic prenatally diagnosed hydronephrosis may progress to needing surgery; no biomarker supporting the identification of these cases is currently available. The aim of the study was to assess the role of Plasma Renin Activity (PRA) as a discriminatory factor to identify patients with asymptomatic prenatally diagnosed hydronephrosis who require close monitoring and are at-risk for surgery., Methods: The study group consists of 30 children prenatally diagnosed with asymptomatic unilateral hydronephrosis, initially managed with medical follow-up. Pyeloplasty was indicated if patients became symptomatic or if there was a significant drop in split renal function (SRF) during follow-up. An association was sought between PRA and renal parameters in post-hoc analysis., Results: During the mean follow-up of 55.5 ± 8.2 months, 13/30 (43.3%) patients developed delayed drainage and 8/30 (26.6%) underwent pyeloplasty. Mean PRA was higher at presentation in the group which later presented with a drop in differential kidney function  ≥ 10%, while it was within the normal range for age in the other patients. Before pyeloplasty, progression to delayed drainage coincided with a drop in SRF and a rise in PRA. While PRA levels normalized after pyeloplasty, SRF improved but did not reach initial values. A mean rise of 68.9% in PRA preceded current indications for surgery by 27.5 ± 9.5 months., Conclusions: A progressive increase in PRA in children with asymptomatic prenatally diagnosed hydronephrosis reflects obstructive stress in the tubulo-interstitial compartment. This stress is relieved by pyeloplasty and is reflected by a drop in PRA after surgery. PRA can, thus, serve as the discriminatory factor to identify hydronephrosis patients 'at-risk' for surgery even before the current criteria for pyeloplasty are met., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

The effects of Carbon ion radiation (C-ion) alone or in combination with fused toes homolog (FTS) silencing on Notch signaling were investigated in uterine cervical cancer cell lines (ME180 and CaSki). In both cell lines, upon irradiation with C-ion, the expression of Notch signaling molecules (Notch1, 2, 3 and cleaved Notch1), γ-secretase complex molecules and FTS was upregulated dose-dependently (1, 2 and 4 Gy) except Notch1 in ME180 cells where the change in expression was not significant. However, overexpression of these molecules was attenuated upon silencing of FTS. The spheroid formation, expression of stem cell markers (OCT4A, Sox2 and Nanog) and clonogenic cell survival were reduced by the combination as compared to FTS silencing or C-ion irradiation alone. Additionally, immunoprecipitation and immunofluorescence assay revealed interaction and co-localization of FTS with Notch signaling molecules. In conclusion, FTS silencing enhances the radio-sensitivity of the cervical cancer cells to C-ion by downregulating Notch signaling molecules and decreasing the survival of cancer stem cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 D.S., Chaturvedi, Shimokawa, Kim and Park.)

Background: With standardization of laparoscopic technique of groin hernia repair, the focus of surgical outcome has shifted to lesser studied parameters like sexual function and fertility., Methods: This prospective randomized study was conducted in a single surgical unit at a tertiary care hospital. A sample size of 144 was calculated with 72 in each group (Group 1 TEP and Group 2 TAPP). Primary outcomes measured included comparison of sexual function using BMFSI, qualitative semen analysis and ASA levels between patients undergoing TEP or TAPP repair. Semen analysis and ASA was measured pre-operatively and 3 months post-operatively., Results: A total of 145 patients were randomized into two groups, TAPP (73) and TEP (72) patients. Both the groups were comparable in terms of demographic profile and hernia characteristics with majority of the patients in both the groups having unilateral inguinal hernia (89.0% in TAPP group and 79.2% in TEP group). Both the groups showed statistically significant improvement in overall sexual function score (BMFSI) at 3 months; however, there was no inter group difference. Both the groups were also comparable in terms of ASA and qualitative semen analysis., Conclusion: Both TEP and TAPP repair are comparable in terms of sexual function and effect on semen analysis. Laparoscopic repair improves the overall sexual functions in patients with groin hernia.

Two fractions, small and big (CpL-S, CpL-B), from Cryptosporidium parvum lysate (CpL) were prepared and its radioprotective activity was evaluated on normal cells. Both fractions improved cell viability of normal cells in a dose-dependent manner. 20 μg CpL-S and CpL-B improved cell viability of 10 Gy irradiated COS-7 cells by 38% and 34% respectively, while in HaCat cells 16% and 18% improved cell viability was observed, respectively. CpL-S scavenged IR-induced ROS more effectively compared to the CpL-B, 50% more in COS-7 cells and 15% more in HaCat cells. There was a significant reduction of γH2AX, Rad51, and pDNA-PKcs foci in CpL-S treated cells compared to control or CpL-B group at an early time point as well as late time point. In 3D skin tissue, CpL-S reduced the number of γH2AX positive cells by 31%, compared to control, while CpL-B reduced by 9% (p < 0.005) at 1 h post 10 Gy irradiation and 22% vs 6% at 24 h post-IR (p < 0.005). Taken together, CpL-S significantly improved cell viability and prevented radiation-induced DNA damage in normal cells as well as 3D skin tissues by effectively scavenging ROS generated by ionizing radiation. CpL-S can be a candidate for radioprotector development., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study was undertaken to compare ophthalmic artery blood flow in eyes having primary open angle glaucoma (POAG) with age matched non glaucomatous eyes using the technique of Color Doppler imaging in Indian patients. One hundred patients of either sex over 40 years of age were divided into two groups of 50 patients each. Group 1 included 50 patients diagnosed with POAG whereas group 2 included patients who did not have POAG. Tests like visual fields and OCT RNFL were conducted and a radiologist assessed the ophthalmic artery blood flow using Color Doppler imaging. Hemodynamic calculations of ocular blood flow were done using the parameters of resistivity index (RI) and pulsatility index (PI). Statistically significant increase in the values of RI and PI were noted in patients with POAG as compared to those who did not have POAG., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Oman Ophthalmic Society.)

Introduction: Febrile neutropenia is a common cause in morbidity and mortality during treatment of hematological neoplasms., Methods: Subjects included all cases admitted under hematology department with febrile neutropenia from February to June 2018. Each febrile episode was investigated by standard investigations (Blood culture, Chest x ray etc.); Procalcitonin (PCT) and c reactive protein (CRP) was sent at fever onset 0, 24, 48 h, day 7 and day 14., Results: Data was analyzed for 52 febrile episodes in 50 patients. PCT cut off value at 24 h of ≤1.2 ng/ml had a sensitivity and specificity of 62.5% and 87.5% for discriminating Invasive fungal infection (IFI) and Microbiologically documented infection (MDI) (p = 0.033). PCT had a negative predictive value of 70% for the diagnosis of IFI as compared to MDI. CRP cut off >160 mg/dl at 48 h was suggestive of fever due to fungal infection with a sensitivity of 100%, specificity of 48%, PPV of 33.3% and NPV of 100%. CRP at 24 and 48 h of fever was useful to distinguish non-infectious causes of fever from infectious causes., Conclusion: PCT at 24 h and CRP at 48 h was useful in identifying fungal infection. CRP was a better marker when compared to PCT for identifying disease fever., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Strong association exists between celiac disease and autoimmune endocrinopathies such as type I diabetes and hypothyroidism; there is a lack of data on the involvement of other endocrine organs such as pituitary-gonadal axis. Furthermore, there is lack of data on the spectrum of involvement of endocrine organs varying from organ autoimmunity to subclinical and clinical disease. We evaluated consecutive treatment-naïve patients with celiac disease (CeD) for clinical and subclinical endocrinopathies., Methods: Of 154 screened, 74 treatment-naïve patients with CeD were recruited. They underwent hormonal and/or functional assessment of beta cell of pancreas, thyroid gland, pituitary-gonadal axis, and parathyroid glands., Results: Of the 74 patients with CeD, 31 (41.9%) had at least one clinical or subclinical endocrinopathy and 9 (12.2%) had multiple endocrinopathies. Most common of them were clinical or subclinical type I diabetes and autoimmune thyroid disease. Interestingly, 8 (10.8%) patients also were found to have functional hypopituitarism and 7/54 (12.9%) having isolated hypogonadotropic hypogonadism., Conclusions: Patients with CeD have high percentages of not only clinical endocrinopathy including pituitary-gonadal axis dysfunction but also subclinical endocrinopathy. Whether commencement of gluten-free diet will lead to reversal of subclinical endocrinopathies requires further follow up studies.

Aim: Patients with celiac disease (CeD) are prone to develop other autoimmune diseases such as autoimmune thyroid disease and type 1 diabetes. While 7.5% of first-degree relatives (FDRs) of patients with CeD develop CeD, it is not clear whether FDRs of patients with CeD are at higher risk of developing autoimmune thyroid disease., Methods: In this prospective case-control study, we recruited 194 FDRs (males 53.1%) of 91 patients with CeD and 140 age-matched healthy controls (males 76.4%). They were screened for CeD using anti-tissue transglutaminase antibodies (anti-tTG Ab) and thyroid disease using a symptom questionnaire, anti-thyroid peroxidase antibodies (anti-TPO) and serum thyroid-stimulating hormone (TSH). Subjects having positive anti-TPO but a normal TSH were classified as having thyroid autoimmunity and those with elevated TSH with or without positive anti-TPO Ab were classified as having autoimmune thyroid dysfunction., Results: The prevalence of thyroid autoimmunity and autoimmune thyroid dysfunction in FDRs was significantly higher than that in healthy controls (17.5% vs. 5.0%, p < 0.01; 11.8% vs. 3.5%, p < 0.01), respectively. A significantly higher number of FDRs had a positive anti-tTG Ab in comparison with controls (13.9% vs. 2.2%, p < 0.001). Amongst FDRs having thyroid autoimmunity, 44.1%, 47.0% and 8.8% were siblings, parents and children of patients with CeD, respectively. Familial clustering was seen only in 1 family., Conclusion: FDRs of patients with CeD have 3-fold higher risk of developing autoimmune thyroid disorders and associated thyroid dysfunction. Therefore, it is advisable for early screening of FDRs for CeD and associated thyroid autoimmune through screening measures.

Though the existence of cancer stem cells remained enigmatic initially, over the time their participation in tumorigenesis and tumor progression has become highly evident. Today, they are also appreciated as the causal element for tumor heterogeneity and drug-resistance. Cancer stem cells activate a set of molecular pathways some of which are triggered by the unique mechanical properties of the tumor tissue stroma. A relatively new field called mechanobiology has emerged, which aims to critically evaluate the mechanical properties associated with biological events like tissue morphogenesis, cell-cell or cell-matrix interactions, cellular migration and also the development and progression of cancer. Development of more realistic model systems and biophysical instrumentation for observation and manipulation of cell-dynamics in real-time has invoked a hope for some novel therapeutic modalities against cancer in the future. This review discusses the fundamental concepts of cancer stem cells from an intriguing viewpoint of mechanobiology and some important breakthroughs to date.

Background and Objective: The modulatory role of prolactin in autoimmune regulation is well established. Hyperprolactinemia is often associated with autoimmune disease like systemic lupus erythematosus and autoimmune thyroid diseases. The objective was to compare levels of direct and indirect autoimmune factors in different categories of hyperprolactinemia cases and predict the direction of association between hyperprolactinemia and autoimmune factors, if any., Methods: A total of 102 hyperprolactinemia cases (>100 ng/mL serum prolactin level) were included along with 24 controls. Among 102 hyperprolactinemia cases, there were 36 idiopathic cases, 19 pituitary adenoma cases, 36 drug-induced cases, and 11 cases associated with other secondary/systemic diseases (chronic renal failure, chronic hepatic failure, etc)., Measurements: Direct autoimmune markers, IL-2, IFN-γ, IL-4, and IL-5, were measured in serum by ELISA. Indirect autoimmune markers, anti-TPO, anti-tg, anti-CCP, VDRL, platelet count, and aPTT, were measured as per laboratory-defined protocol., Results: Serum levels of IL-4 and anti-TPO were significantly high in idiopathic hyperprolactinemia cases. Serum IL-4 levels were also significantly high in pituitary adenoma cases, drug-induced cases, and in cases with other secondary causes of hyperprolactinemia. Serum anti-TPO levels were also significantly high in drug-induced hyperprolactinemia cases., Conclusion: No significant difference in autoimmune factors is observed between macroprolactinemia and true hyperprolactinemia. Serum IL-4 and anti-TPO were high in all categories of hyperprolactinemia. This suggests a possible association of hyperprolactinemia with autoimmune conditions (high IL-4 and anti-TPO), mostly subclinical. Thus, hyperprolactinemia case with serum prolactin level >100 ng/mL may require long-term follow-up for the development of autoimmune disease in future., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Macroprolactinemia is characterized by predominance of macroprolactin molecules in circulation and generally has extra-pituitary origin. Macroprolactin is viewed as biologically inactive, therefore asymptomatic, and thus may not require any treatment or prolonged follow-up. In addition, data on prevalence of macroprolactinemia and its clinical manifestation are also rare. Therefore, the present study was aimed to find out prevalence of macroprolactinemia and its association, if any, with reproductive manifestations., Material and Methods: Macroprolactin was measured in 102 hyperprolactinemia cases (>100 ng/ml prolactin level), 135 physiological hyperprolactinemia cases (50 pregnant and 85 lactating females; >100 ng/ml prolactin level) and 24 controls. Poly ethylene glycol (PEG) precipitation method was carried out to screen macroprolactin. Prolactin recovery of <25% was considered overt macroprolactinemia. Detailed clinical data was recorded which included complete medical history, physical examination and hormone measurements besides CT/MRI for pituitary abnormalities., Results: Prevalence of macroprolactinemia was 21.57% (22/102) in hyperprolactinemia (prolactin >100 ng/ml). There was no case of macroprolactinemia in physiological hyperprolactinemia, or healthy control females. Reproductive manifestations were present in 72.73% (16/22) macroprolactinemia cases, out of which macroprolactinemia was the sole cause of associated reproductive manifestations in 68.7% (11/16) cases. Reversal of reproductive dysfunction/s was observed in five cases with appropriate treatment for high macroprolactin., Conclusion: Macroprolactinemia prevalence was found to be 21.5%, out of which 72.73% cases had associated reproductive dysfunctions.

Study Design: Single-center, observational, case-control study., Purpose: Comparison and analysis of the metabolic and coagulative profiles in patients with idiopathic scoliosis, patients with congenital scoliosis, and healthy controls., Overview of Literature: Serum melatonin deficiency has been a controversial topic in the etiopathogenesis of scoliosis. Low bone mineral density, low vitamin D3 levels, and high parathyroid hormone levels are common metabolic abnormalities associated with scoliosis that may be responsible for its pathogenesis. In addition to metabolic defects, several studies have shown coagulation defects that either persist from the preoperative period or occur during surgery and usually lead to more than the expected amount of blood loss in patients undergoing deformity correction for scoliosis., Methods: The study population (n=73) was classified into those having congenital scoliosis (n=31), those with idiopathic scoliosis (n=30), and healthy controls (n=12). After detailed clinicoradiological evaluation of all the subjects, 10-mL blood samples were collected, measured, and analyzed for various metabolic and coagulation parameters., Results: The mean serum melatonin levels in patients with idiopathic scoliosis were significantly lower than those in the healthy controls. Although the mean serum melatonin level in the congenital group was also low, the difference was not statistically significant. Serum alkaline phosphatase and parathyroid hormone levels were higher in the scoliosis groups, whereas the vitamin D level was lower. No differences were observed in the coagulation profiles of the different groups., Conclusions: Low serum melatonin levels associated with scoliosis can be a cause or an effect of scoliosis. Moreover, low bone mineral density, high bone turn over, and negative calcium balance appear to play an important role in the progression, if not the onset, of the deformity.

Curcumin (cur) has been comprehensively studied for its various biological properties, more precisely for its antitumor potential and it has shown the promising results as well. On the other hand, Chlorin e6 (Ce6) has mostly been used as a photosensitizer in photodynamic therapy (PDT) against a variety of carcinomas. In the present study, we have synthesized a series of Chlorin e6-curcumin (Ce6-cur) conjugates and investigated their photosensitizing potential against pancreatic cancer cell lines. All the synthesized compounds were characterized by UV, 1 H NMR, 13 C NMR and LC-MS. These Ce6-cur conjugates showed better physicochemical properties and higher singlet oxygen generation capability. The cellular uptake was studied in AsPC-1 cells using fluorescence-activated cell sorting (FACS). Compound 17 was rapidly internalized within 30 min and sustained for 24 h. Compound 17 showed excellent PDT efficacy with IC 50 of 40, 35 and 41 nM against AsPC-1, MIA PaCa-2 and PANC-1 respectively with exceptional dark/phototoxicity ratio in the range of 2371-7500. Moreover, the treatment of compound 17 upregulated the expression of BAX, Cytochrome-C and cleaved caspase 9 while downregulating the Bcl-2 expression an anti-apoptotic protein marker. These results demonstrate outstanding capability of compound 17 as a potent photosensitizer which could improve the PDT efficacy in pancreatic cancer patients., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: The relationship between cortisol level and sepsis is not known in Indian patients of severe sepsis/septic shock., Aims: The study was done to determine the optimal range of cortisol levels, defining the adrenocortical response, and predicting the mortality, if possible, in the above type of patients., Settings and Designs: The study was a single-centered prospective cohort study, conducted in a tertiary referral center, North India., Materials and Methods: Sixty patients with severe sepsis ( n = 30) and septic shock ( n = 30) were recruited. Basal and postcosyntropin (1 μg)-stimulated cortisol levels were measured, and all patients were closely monitored with daily assessments of clinical and laboratory variables. Western diagnostic criteria were followed for defining adrenal insufficiency (AI). The end point was the survival assessed at day 28 or death, whichever came earlier., Results: The mean basal (T0) and poststimulation (T30) cortisol levels were 31.77 ± 15.9 μg/dL and 37.58 ± 17.31 μg/dL, respectively. In all sepsis patients, 48.33% qualified as AI at T0 ≤ 24 μg/dL, 61.67% at delta cortisol (Δ = T30-T0) ≤7 μg/dL, and 78.33% at Δ ≤9 μg/dL. Using receiver operating characteristic curve, the area under the curve (AUC) was 0.4954, signifying poor prediction to death., Conclusions: Indians have completely different characteristics of cortisol levels in sepsis patients, in comparison to the Western data. They have higher range of basal cortisol levels, higher percentage of AI, and an inability to predict mortality with the cortisol levels. Hence, there is requirement of an international study to confirm the dichotomy of the results., Competing Interests: There are no conflicts of interest.

There are contrary reports of association of lead and cadmium with the decline in semen quality. This study evaluates whether seminal lead (Pb) and cadmium (Cd) at environmental concentration are associated with altered semen quality. We conducted a study of healthy fertile and infertile men 20-43 years of age attending the Andrology Laboratory of Reproductive Biology Department for semen analysis. The semen analysis was carried out according to the WHO 2010 guidelines. Seminal lead and cadmium were estimated by ICP-AES. The lead and cadmium values were significantly higher in infertile subjects. A negative association between seminal lead or cadmium concentration and sperm concentration, sperm motility and per cent abnormal spermatozoa was found. This study shows that exposure to Pb (5.29-7.25 μg dl(-1) ) and cadmium (4.07-5.92 μg dl(-1) ) might affect semen profile in men. Age, diet, smoking and tobacco chewing habits may have an influence on the increase in exposure to Pb and Cd in the individual subjects., (© 2014 Blackwell Verlag GmbH.)

Bee venom (BV) therapy is a type of alternative medical treatment used to treat various diseases in oriental medicine. The mechanisms underlying the effects of BV remain poorly understood. In the present study, we evaluated the antiviral effect of BV on cervical carcinoma cell lines (CaSki, HeLa, C33A and TC-1). BV treatments resulted in a more significant suppression of cell growth in HPV 16-infected cells (CaSki) and a lesser suppression in HPV 18-infected cells (HeLa). However, less suppression was observed in HPV-negative C33A cells. In 10 µg/ml BV-treated CaSki cells, the mRNA expression and protein levels of HPV16 E6 and E7 were significantly decreased by BV, while HPV18 E6 and E7 mRNA expression levels were not significantly altered by 10 µg/ml BV-treated HeLa cells. The antitumor effects of BV were in accordance with in vitro data, in restricting tumor growth in vivo and were much more effective on the suppression of tumor growth. Furthermore, the mRNA and protein expression levels of HPV16 E6 and E7 were decreased by BV in TC-1 tumors. These findings demonstrated the antiviral effects of BV in HPV-infected cervical cancer cells and the anticancer effects of BV in HPV16 E6/E7-expressed TC-1 tumors. Collectively, BV plays a differential role in suppressing HPV16-infected cells (CaSki cells) and HPV18-infected cells (HeLa cells) by the downregulation of E6/E7 protein of HPV16/18.

Environmental toxicants viz lead or cadmium and phthalate esters (di(2-ethylhexyl) phthalate [DEHP], dibutyl phthalate [DBP], and diethyl phthalate [DEP]) widely found in different environmental strata are linked to deteriorating male reproductive health. The objective was to assess the relationships between the seminal lead, cadmium, and phthalate (DEHP, DBP, DEP) concentrations at environmental level and serum hormone levels and semen quality in non-occupationally exposed men and specify the effect of individual and combined exposure of toxicants on semen quality. A study of 60 male partners of couples attending the Andrology Laboratory of the Reproductive Biology Department, All India Institute of Medical Sciences (AIIMS), New Delhi, India for semen analysis to assess their inability to achieve a pregnancy was selected for the study. The results of univariate and stepwise multiple regression analysis in the unadjusted model showed a significant correlation between lead or cadmium and phthalates DEHP/DBP/DEP and sperm motility, sperm concentration, and DNA damage. After adjusting for potential confounders, an association with lead or DEHP was only observed. The present data shows that lead (Pb) or cadmium (Cd) or phthalates might independently contribute to decline in semen quality and induce DNA damage. Phthalates might influence reproductive hormone testosterone. These findings are significant in light of the fact that men are exposed to a volley of chemicals; however, due to the small sample size, our finding needs to be confirmed in a larger population.

Cancer is characterized by the dysregulation of cell signaling pathways at several steps. The majority of current anticancer therapies involve the modulation of a single target. A tumor-targeting drug-delivery system consists of a tumor detection moiety and a cytotoxic material joined directly or through a suitable linker to form a conjugate. Photodynamic therapy has been used for more than 100 years to treat tumors. One of the present goals of photodynamic therapy research is to enhance the selective targeting of tumor cells in order to reduce the risk and extension of unwanted side-effects, caused by normal cell damage. Sonodynamic therapy is a promising new treatment for patients with cancer. It treats cancer with ultrasound and sonosensitive agents. Porphyrin compounds often serve as photosensitive and sonosensitive agents. The combination of these two methods makes cancer treatment more effective. The present review provides an overview of photodynamic therapy, sonodynamic therapy, sono-photodynamic therapy and the four sensitizers which are suitable candidates for combined sono-photodynamic therapy., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Scientific concern exists about the toxic effect of dichlorodiphenyldichloroethylene (p, p'-DDE) and lindane on male infertility, and the mechanism underlying male reproductive toxicity of this pesticide remains unanswered. We investigated not only the possible association between the chlorinated pesticide levels and semen quality in nonoccupationally exposed men, but also the probable mode of action using mitochondrial membrane potential (MMP), reactive oxygen species (ROS), lipid peroxidation (LPO), and sperm chromatin structure assay (SCSA). A study in 278 men (21-40 years old) who visited Obstetrics and Gynecology Department, KGMU, Lucknow, for semen analysis was conducted. We performed semen analysis according to the WHO guidelines, while p, p'-DDE and lindane analysis was done by the GLC and LPO by the spectrophotometer, and the sperm mitochondrial status, ROS, and SCSA with the flow cytometer. The questionnaire data showed no significant difference in the demographic characteristics between the two groups, i.e., trying to conceive >1 year and proven fertility. However, a significant difference in the concentration of p, p'-DDE and lindane was observed between the groups. When the subjects were divided among four categories by quartile of exposure, the subjects in the highest quartile showed low sperm motility as compared to the subjects in the lowest quartile. Pearson's correlation showed a significant negative correlation between semen p, p'-DDE, lindane level, and sperm quality and positive association with the number of cells with depolarized mitochondria, elevation in ROS production and LPO, and DNA fragmentation index (DFI). The findings are suggestive that these toxicants might cause a decline in semen quality, and these effects might be ROS, LPO, and mitochondrial dysfunction mediated.

Human data on the relationship of semen quality with pesticide and metals are mostly inconsistent. The purpose of the study is to confirm the toxicity of organochlorine pesticide β- and γ-hexachlorocyclohexane (HCH), DDE and DDD, and metals lead or cadmium on sperm motility in epidemiological study among fertile and infertile men and to determine whether in vivo and in vitro results are in the same direction. Semen analysis and estimation of the toxicants were done in 60 fertile and 150 infertile men. In the in vitro studies, sperm were exposed to the highest levels of these toxicants found in vivo, as well as five and ten times higher, and to the mixture of all compounds. The study assesses sperm viability and motility for a period ranging between 30 min and 96 h. Epidemiological data showed an inverse correlation of toxicant with sperm motility. In vitro study showed that γ-HCH and lead after 12 h, cadmium after 8 h, and coexposure to toxicants after 6 h of exposure caused significant concentration- and duration-dependent decline in sperm motility. Data of in vitro study were concurrent with epidemiological finding that might be useful in establishing the possible association between exposure and effect of these selected pollutants on sperm motility.

Human papillomavirus (HPV) has drawn great attention globally because of its association with virtually all (99 %) cases of cervical cancer. HPV virus-like particles (VLPs) have been implicated as an effective HPV vaccine candidate. In this study, we optimized the relevant parameters for bacterial production of high-risk HPV16 and HPV18 VLP L1 proteins. The combination of glutathione S-transferase fusion and late log phase culture induction enhanced the solubility and yield of HPV L1 proteins. For detection and quantification of HPV-16 and -18 antibodies, a Luminex-based competitive immunoassay was developed for use in vaccine clinical trials. The characteristics of the assay that were optimized included monoclonal antibody specificity, conjugation of VLP to microspheres, VLP concentration, antibody concentration, dilution of samples, and incubation time. No cross-reactivity occurred. This immunoassay was proven to be sensitive and accurate, and is potentially valuable for vaccine candidate evaluation and clinical use.

Aim: To study renin angiotensin system (RAS) activity after posterior urethral valve ablation and the role of early induction of angiotensin converting enzyme-inhibitors (ACE-I) on the outcome of renal function., Materials and Methods: Thirty four children underwent valve ablation in which therapy with ACE-I was started 40.5 ± 4.1 (range 32-47 months) formed the study group. Post-ACE-I data were collected after mean duration of 18.2 ± 4.0 (12-28 months). Plasma renin activity (PRA), urinary micro albumin, glomerular filtration rate (GFR), and serum creatinine, before and after therapy were monitored., Results: Therapy with ACE-I resulted in a fall in micro albuminuria by 45.7% and 42.0% in patients without and with vesico ureteral reflux, respectively, and improvement in split renal function by 6.6% and 5.9% GFR respectively. A similar response was noted in patients without and with renal scars., Conclusion: The decline in renal function after valve ablation is accompanied by activation of RAS reflected in a gradual rise in PRA. Therapy with ACE-I stabilizes and then improves renal function, thereby, retarding the pace of renal damage.

The purpose of the present study was to evaluate multiplex liquid assay-based measurement of multiple ovarian cancer-associated biomarkers such as hemoglobin, haptoglobin and apolipoprotein E, together with CA125, which has been widely used in the diagnosis of ovarian cancer, in order to provide a higher diagnostic power. We measured the serum levels of CA125, hemoglobin, haptoglobin and apolipoprotein E from the serum of 76 healthy individuals and 69 ovarian cancer patients using a multiplex liquid assay system, Luminex 100. The results were analyzed according to normal versus ovarian cancer, tumor stages and tumor histology. In addition, to validate the use of these biomarkers for the diagnosis of ovarian cancer, the sensitivity and specificity of each biomarker was analyzed by its receiver operating characteristics (ROC) curve. The serum levels of all four biomarkers in ovarian cancer patients were significantly higher than those of healthy individuals. When CA125 was combined with the biomarkers, the overall sensitivity and specificity were significantly improved in the ROC curve, which showed 95 and 75% sensitivity and specificity, respectively. At 95% specificity for all stages the sensitivity increased to 75% compared to 41% for CA125 alone. For stage I+II increased the sensitivity to 68% from 36% for CA125 alone. For stage III+IV the corresponding values were 100 and 95%, respectively. Taken together, the new combination of hemoglobin, haptoglobin and apolipoprotein E with CA125 significantly improved both the sensitivity and the specificity of ovarian cancer diagnosis compared with those of individual biomarkers. These findings suggest the benefit of the combination of these markers for the diagnosis of ovarian cancer.

Our aim was (i) to investigate the hypothalamo-hypophyseal-gonadal axis in hyperthyroid Indian males, (ii) to rule out the modulatory role of adrenal steroids on it and (iii) to determine if the simultaneous rise in oestradiol and luteinising hormone (LH) in hyperthyroid males is due to a positive feedback action of oestradiol on pituitary LH release. Age- and BMI-matched men were divided into two groups, I, euthyroid subjects (n = 17) and II, hyperthyroid patients (n = 12) on the basis of their thyroid hormone levels. Serum levels of thyroid-stimulating hormone, triiodothyronine, thyroxine, LH, follicle-stimulating hormone (FSH), prolactin, E(2), T, P(4), sex hormone binding globulin and dehydroepiandrosterone sulphate (DHEAS) were assayed. Mean levels of T and E(2) were approximately two times higher in group II in comparison with group I. DHEAS levels were similar in both groups ruling out any adrenal involvement. Mean serum LH level was 2.6 folds higher in group II in comparison with group I. Mean serum levels of FSH were higher in group II, it was marginally nonsignificant. On the basis of these and previous observations, we hypothesise that endocrinological dimorphism in human male and female is not rigid; a sustained rise in serum oestradiol probably induces a positive feedback action on pituitary leading to elevated gonadotrophin levels., (© 2012 Blackwell Verlag GmbH.)

The aim of this study was to determine serum selenium (Se) levels during the development of liver disease as well as the possible Se supplementation benefits in liver disease patients. Serum was collected from 187 patients with liver diseases and 120 normal healthy people living in Seoul. The samples were collected at the Kangnam St. Mary's Hospital College of Medicines, The Catholic University of Korea, in accordance with procedures approved by the Institutional Review Board of the Catholic University of Korea. Serum Se levels were quantified by inductively coupled plasma mass spectrometry and were compared between healthy and liver diseases patients. Se levels were 92.65 ± 32.50 μg/l in hepatitis infection, 92.33 ± 30.66 μg/l in hepatitis B virus infection and 96.41 ± 51.50 μg/l in hepatitis C virus infection, 96.42 ± 32.80 μg/l in cirrhosis, and 67.47 ± 14.30 μg/l in hepatoma patients. Findings were significantly lower in hepatitis and hepatoma as compared with the healthy participants (P < 0.001). The Se level of the healthy population was 108.38 ± 29.50, 119.37 ± 28.31 for males and 97.87 ± 26.99 μg/l for females. Our data shows the same parallelism between liver disease progression and decrease of Se levels except in the case of liver cirrhosis. And also, our study confirms the previous findings of significantly lower Se levels in Korean hepatoma patients. Se levels that decrease parallel to liver disease progression should be further integrated and analyzed with liver function blood biomarkers.

Objective: The aim of this study was to identify novel genes following genomic DNA copy number changes using a genome-wide array-based comparative genomic hybridization (array-CGH) analysis in uterine leiomyosarcoma (ULMS)., Methods: Genomic DNA copy number changes were analyzed in 15 cases of ULMS from St Mary's Hospital of the Catholic University of Korea. The paraffin-fixed tissue samples were micro-dissected under microscope, and DNA was extracted. Array-based CGH and genomic polymerase chain reaction were carried out with statistical analyses such as hierarchical clustering and Gene Ontology., Results: All of 15 cases of ULMS showed specific gains and losses. The percentage of average gains and losses were 8.4 and 16.6 %, respectively. The analysis limit of average gains and losses was 40 %. The regions of high level of gain were 1q23.3, 7p14.2, 7q34, 7q35, 7q36.3, 13q34, and 16p13.3. And the regions of homozygous loss were 2q21.1, 2q22.1, 2p23.2, 12q23.3, 4q21.22, 4q34.3, 11q24.2, 12q23.3, 13q13.1, 13q21.33, and 14q24.3. In ULMS samples, recurrent regions of gain were 1p36.33, 1p36.32, 5q35.3, 7q36.3, and 8q24.3 and recurrent regions of loss were 1p31.1-p31.3, 1p32.1-p32.3, 2p12, 2p13.3, 2p14, 2p16.2-p16.3, 2q12.1-q12.3, 2q21.1-q21.2, 2q22.2-q22.3, 2q34, 2q36.1-q36.3, 5q21.3, 5q23.3, 5q31.1, 6p11.2, 6p12.1, 10q11.23, 10q21.2-q21.3, 10q23.2, 10q23.31, 10q25.1-q25.2, 10q25.3, 10q26.13, 10q26.2-q26.3, 11p11.2, 11p11.12, 11p12, 11p13, 11p15.4, 11q23.1-q23.2, 11q23.3, 13q14.12, 13q14.13-13q14.2, 13q14.2, 13q14.2, 13q14.3, 13q21.33, 13q22.1-q22.3, 14q24.2, 14q24.3, 14q31.1, 14q32.33, 15q11.2-q13, 15q14, 16q22.3, 16q23.1, 16q23.2, 16q24.1, 20p12.1, and 21q22.3. Representative frequently gained BAC clones encoded genes were HDAC9, CRR9, SOX18, PTPRN2, SKI, SOLH, and KIAA1199. The genes encoded by frequently lost BAC clones were LOC150516 and AMY2A. A subset of cellular processes from each gene were clustered by Gene Ontology database., Conclusions: The present study using array-CGH analyses sought a deeper elucidation of the specific genomic alterations related to ULMS. The high resolution of array-CGH combined with human genome database would give a chance at identifying relevant target genes.

Chlorin-based photosensitizers in photodynamic therapy are the promising anticancer agents, but some of their properties such as specific-targeting to tumor need to be improved. The aim of this study was to synthesize chlorin-based unsaturated fatty acid conjugates to obtain an optimal photosensitizers. Thus four chlorin-based fatty acid conjugates were successfully synthesized through an esterification reaction using carbodiimide coupling reagents in enough yields. Then, structures of these conjugates were confirmed by (1)H NMR, MALDI-MS, and UV-vis spectroscopy. Furthermore, their in vitro phototoxicity and cellular uptake were evaluated on TC-1 lung cancer cell line and HeLa cell line., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Mammalian testis functions at a temperature and oxygen tension (pO(2)) lower than the core body. Hypoxia-inducible factor-1α (HIF-1α) mediates the adaptive responses to hypoxia such as production of angiogenic vascular endothelial growth factor (VEGF) in a variety of cells and tissues. VEGF production in Leydig cells is stimulated by luteinising hormone (LH)/cAMP. We have conducted experiments to find out whether HIF-1α is involved in LH/cAMP-induced secretion of VEGF by Leydig cell-derived MA-10 cells. Both cobalt chloride (CoCl(2)), an inducer of hypoxia, and 8-Br-cAMP enhanced HIF-1α activity followed by an increase in VEGF secretion. However, there was no change in mRNA levels of HIF-1α. Inhibition of HIF-1α activity by cyclosporine A (CsA) inhibited a rise in VEGF production in response to CoCl(2) as well as 8-Br-cAMP. Inhibitors of protein kinase A (PKA), extracellular regulated kinase 1/2 (ERK1/2) and phosphatidyl inositol-3 kinase/Akt (PI3-K/Akt) inhibited the increase in VEGF levels in response to both CoCl(2) and 8-Br-cAMP. The data suggest that HIF-1α is a mediator of hypoxia- as well as 8-Br-cAMP-stimulated production of VEGF in MA-10 cells; both the stimuli act through a common signalling cascade., (© 2011 Blackwell Verlag GmbH.)

The accurate genotyping of human papillomavirus (HPV) is clinically important because the oncogenic potential of HPV is dependent on specific genotypes. Here, we described the development of a bead-based multiplex HPV genotyping (MPG) method which is able to detect 20 types of HPV (15 high-risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68 and 5 low-risk HPV types 6, 11, 40, 55, 70) and evaluated its accuracy with sequencing. A total of 890 clinical samples were studied. Among these samples, 484 were HPV positive and 406 were HPV negative by consensus primer (PGMY09/11) directed PCR. The genotyping of 484 HPV positive samples was carried out by the bead-based MPG method. The accuracy was 93.5% (95% CI, 91.0-96.0), 80.1% (95% CI, 72.3-87.9) for single and multiple infections, respectively, while a complete type mismatch was observed only in one sample. The MPG method indiscriminately detected dysplasia of several cytological grades including 71.8% (95% CI, 61.5-82.3) of ASCUS (atypical squamous cells of undetermined significance) and more specific for high grade lesions. For women with HSIL (high grade squamous intraepithelial lesion) and SCC diagnosis, 32 women showed a PPV (positive predictive value) of 77.3% (95% CI, 64.8-89.8). Among women >40 years of age, 22 women with histological cervical cancer lesions showed a PPV of 88% (95% CI, 75.3-100). Of the highest risk HPV types including HPV-16, 18 and 31 positive women of the same age groups, 34 women with histological cervical cancer lesions showed a PPV of 77.3% (95% CI, 65.0-89.6). Taken together, the bead-based MPG method could successfully detect high-grade lesions and high-risk HPV types with a high degree of accuracy in clinical samples.