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Background: To evaluate the relation between serum-25-hydroxy Vitamin-D levels (S25OHVDL) and concurrent chemoradiation therapy (CTRT) toxicities in patients of head and neck squamous cell cancer (HNSCC). Methods: After an institutional ethics committee approval, consecutive HNSCC patients who received radical/adjuvant CTRT were prospectively evaluated. Patients were assessed for CTRT toxicities using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE-v5.0) and the response was evaluated according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST-1.1). S25OHVDL was assessed at the time of the first follow-up. Patients were divided into group A (Optimal) and group B (suboptimal) according to S25OHVDL. The treatment toxicities were correlated with S25OHVDL. Results: Twenty-eight patients were evaluated for the study. S25OHVDL was optimal in eight (28.57%) and suboptimal in 20 patients (71.42%). Mucositis and radiation dermatitis were significantly more in subgroup B (P-value 0.0011 and 0.0505, respectively). Relatively lower but nonsignificant hemoglobin and peripheral white blood cell counts were observed in subgroup B. Conclusion: Suboptimal S25OHVDL was associated with significantly more skin and mucosal toxicities in HNSCC patients treated with CTRT. [ABSTRACT FROM AUTHOR]

Background: Tumor secreting granulocyte-colony-stimulating factor (G-CSF) and/or G-CSF therapy has been documented as a poor prognostic factor. Tumor G-CSF study is a relatively costly and sparsely available investigation. Therefore, this study was undertaken to predict tumor G-CSF score from pretreatment hematological parameters (PTHP) in patients of head-and-neck squamous cell carcinoma (HNSCC). Materials and Methods: This pilot study was performed after institutional ethics committee approval. Consecutive nonmetastatic HNSCC patients of oral cavity, oropharynx, hypopharynx, and larynx registered from February to December 2019 were analyzed. Patients whose PTHP and formalin-fixed-paraffin-embedded tissue were available, were included. PTHP (absolute neutrophil count [ANC], absolute monocyte count [AMC], absolute lymphocyte count [ALC], neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR]) done before any active oncology treatment, were noted. A semiquantitative tumor G-CSF score was calculated. Tumor G-CSF score and PTHP were correlated with clinicopathological factors. Statistical analysis was performed using SYSTAT version 12. Results: Data of 47 eligible patients were analyzed. The median age at presentation was 60 years. The male-to-female ratio was 43:4. The most common head-and-neck subsite was oropharynx (31.92%), and majority of patients presented with Stage IVA disease (51.1%). Higher tumor G-CSF score was significantly associated with a higher T-stage (P = 0.013). Tumor G-CSF score was directly proportional to ANC, AMC, and ALC while it was inversely proportional to NLR and PLR. Regression equations to predict the tumor G-CSF score when PTHP are known, were determined. Conclusions: PTHP can predict the tumor G-CSF score which may guide G-CSF-directed therapy. Future studies with large number of patients are needed to elucidate its clinical use. [ABSTRACT FROM AUTHOR]

Background: Tobacco use is a major public health problem globally and has been identified for initiation and progression of oral cancer. According to WHO, consumption of tobacco has been growing at the rate of 2% to 5% per annum. It is estimated that number of deaths due to tobacco will increase from 3 million per year worldwide to 70 million per year by 2025. Objective: To estimate the prevalence and patterns of tobacco use and tobacco induced oral lesions in rural population of Western Maharashtra. Materials and Methods: This cross sectional epidemiological study was conducted as house to house survey where the selected population was divided in to 30 clusters. 3100 participants were interviewed through a questionnaire. Data on demographics, education, occupation, socioeconomic status were collected along with details regarding tobacco use and duration of the habit. Trained examiners carried out intraoral examination for assessment of incidence of tobacco induced lesions including oral precancer and cancer. Prevalence of tobacco chewing and smoking, and their sociodemographic correlates, were examined. Results: The overall prevalence of tobacco use was 52.70%; the prevalence of smoking and tobacco chewing were 9.48% and 43.22%, respectively. The prevalence of tobacco induced lesions was 34.90%.The study revealed statistically significant correlation between the duration of habit and the occurrence of lesions and significant association between habit and sex. Conclusions: Prevalence of tobacco use is considerably high among the studied population. Demographic and socioeconomic determinants and spatial distribution should be considered while planning tobacco control interventions. [ABSTRACT FROM AUTHOR]

Background: The 'organ distribution' of cancer is often strikingly dissimilar in different groups of population and varies greatly from one community to another and also differs in different communities in the same geographical location, depending on the practices, lifestyles and the influence of deleterious habits like use of tobacco and or alcohol of the people. Among various cancers affecting the human body, oral cancer accounts for nearly one third of it. Objectives: i) To find out the relative frequency of oral cancer in relation to other sites from Hospital Based Cancer Registry (HBCR) ii) To find out the various risk factors associated with oral cancer and iii) To recommend appropriate preventive measures. Methodology: A hospital based retrospective cross sectional study was conducted through case records of oral cancer patients who reported in the year 2013 to Pravara Rural HBCR, Department of Radiotherapy and Oncology, Rural Medical College and Pravara Rural Hospital, Loni, Maharashtra state, India. The case files and registers of oral cancer cases were reviewed to collect personal and clinical data about sex, age, occupation, marital status, education, socioeconomic status, habits like tobacco chewing and cigarette smoking. A predesigned performa (a core form by HBCR programme) was used to collect the data. The statistical analysis was done using SYSTAT for Windows version 12 and categorical data was analysed by using Chi-square test. Results: In all 1328 patients of all cancers visited the hospital during the period January 2013 to December 2013. Out of these, 349 (26.28%) were of oral cancer cases. The sex wise distribution revealed 256 (73.25%) among males and 93(26.65%) among females. Mean age of the patients was 54.98 years, ranging from 15-78 years, 31.23% were more than 65 years of age. The most oral cancer sites among the males and females were those of tongue (37.82%) and buccal mucosa (32.95%) respectively. Tobacco related cancer patients in males were 79% and in females 61% .Conclusion: The present study findings suggest that prevalence of oral cancer is more among tobacco users especially those using tobacco quid which is more common among Indian women which is in line with most of the epidemiological studies about oral cancer in India. There is an urgent need to implement and sustain appropriate preventive measures and oral cancer screening programmes for the community. [ABSTRACT FROM AUTHOR]

Fetal Middle Cerebral Artery Peak Systolic Velocity (MCA-PSV) is being increasingly used for non-invasively diagnosing fetal anemias irrespective of their cause. A study was therefore undertaken to find out what different scenarios can be encountered in the local obstetric population. Doppler ultrasound measurements of fetal MCA-PSV were done in 1200 pregnant women who were referred for antenatal ultrasound between 12 - 40 weeks of gestation. Statistical analysis was done using Microsoft Excel 2007 and SPSS software version 12. The different scenarios encountered in this study were then compiled and are presented here. With increasing gestational age, the value of MCA-PSV was seen to increase correspondingly in all normal fetuses. This correlation between the two was thus positive and was found to be statistically significant (p < 0.05). Abnormally raised values of MCA-PSV were seen in fetuses with severe anemia due to ABO-Rh Isoimmunization which left untreated, ultimately resulted in fetal hydrops. Almost similar and normal values were seen in separate as well as conjoint healthy twins. Abnormally elevated values were seen in twins with discordant growths. Fetal MCA-PSV is very useful to confirm the presence or absence of fetal anemia irrespective of underlying cause in singleton as well as twin pregnancies. For complete assessment, it is essential that the specialist is thoroughly aware of the different scenarios that can be encountered while using this non-invasive method. [ABSTRACT FROM AUTHOR]

Nanophthalmos is a rare, potentially devastating eye condition characterized by small eyes with relatively normal anatomy, a high hyperopic refractive error, and frequent association with angle closure glaucoma and vision loss. The condition constitutes the extreme of hyperopia or farsightedness, a common refractive error that is associated with strabismus and amblyopia in children. NNO1 was the first mapped nanophthalmos locus. We used combined pooled exome sequencing and strong linkage data in the large family used to map this locus to identify a canonical splice site alteration upstream of the last exon of the gene encoding myelin regulatory factor (MYRF c.3376-1G>A), a membrane bound transcription factor that undergoes autoproteolytic cleavage for nuclear localization. This variant produced a stable RNA transcript, leading to a frameshift mutation p.Gly1126Valfs*31 in the C-terminus of the protein. In addition, we identified an early truncating MYRF frameshift mutation, c.769dupC (p.S264QfsX74), in a patient with extreme axial hyperopia and syndromic features. Myrf conditional knockout mice (CKO) developed depigmentation of the retinal pigment epithelium (RPE) and retinal degeneration supporting a role of this gene in retinal and RPE development. Furthermore, we demonstrated the reduced expression of Tmem98, another known nanophthalmos gene, in Myrf CKO mice, and the physical interaction of MYRF with TMEM98. Our study establishes MYRF as a nanophthalmos gene and uncovers a new pathway for eye growth and development., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To evaluate the extent to which mutations in the optineurin (OPTN) glaucoma gene play a role in glaucoma in different populations., Methods: Case-controlled study of OPTN sequence variants in individuals with or without glaucoma in populations of different ancestral origins and evaluate previous OPTN reports. We analyzed 314 subjects with African, Asian, Caucasian and Hispanic ancestries included 229 cases of primary open-angle glaucoma, 51 cases of juvenile-onset open-angle glaucoma, 33 cases of normal tension glaucoma, and 371 controls. Polymerase chain reaction-amplified OPTN coding exons were resequenced and case frequencies were compared to frequencies in controls matched for ancestry., Results: The E50K sequence variant was identified in one individual from Chile with normal tension glaucoma, and the 691&#95;692insAG variant was found in one Ashkenazi Jewish individual from Russia. The R545Q variant was found in two Asian individuals with primary open-angle glaucoma; one of Filipino ancestry and one of Korean ancestry. In addition to presenting OPTN allele frequencies for Caucasian and Asian populations that have been the subject of previous reports, we also present information for populations of Hispanic and black African ancestries., Conclusions: Our study contributes additional evidence to support the previously reported association of the OPTN E50K mutation with glaucoma. After finding an additional 691&#95;692insAG OPTN variant, we can still only conclude that this variant is rare. Combined analysis of our data with data from more than a dozen other studies indicates no association of R545Q with glaucoma in most populations. Those same studies disagree in their conclusions regarding the role of M98K in glaucoma. Our analysis of the combined data provides statistically significant evidence of association of M98K with normal tension glaucoma in Asian populations, but not in Caucasian populations; however, the validity of this conclusion is questionable because of large differences in allele frequencies between and within populations. It is currently not possible to tell how much of the underlying cause of the allele frequency difference is attributable to demographic, technical, or ascertainment differences among the studies.

Purpose: Topical use of dexamethasone has long been associated with steroid induced-glaucoma, although the mechanism is unknown. We applied a strict filtering of comparative microarray data to more than 18,000 genes to evaluate global gene expression of cultured human trabecular meshwork cells in response to treatment with dexamethasone., Methods: Three human trabecular meshwork cell primary cultures from nonglaucomatous donors were incubated with and without dexamethasone for 21 days. Relative gene expression was evaluated by analysis of U133A GeneChip and the results validated using quantitative polymerase chain reaction (PCR)., Results: Application of strict filtering to include only genes with statistically significant differences in gene expression across all three trabecular meshwork cell cultures produced a list of 1,260 genes. Significant changes in signal level were observed, including 23 upregulated and 18 downregulated genes that changed greater than three fold in each of three cell cultures. Using quantitative PCR we found changes greater than a thousand fold for two genes (SLP1 and SAA2) and changes greater than a hundred fold for another five genes (ANGPTL7, MYOC, SAA1, SERPINA3, and ZBTB16)., Conclusions: Expression changes in trabecular meshwork cells in response to dexamethasone treatment indicate that a group of actins and actin-associated proteins are involved in the development of cross-linked actin networks that form in response to dexamethasone. A trend was identified toward decreased expression of protease genes accompanied by an increased expression of protease inhibitors. Such a trend in nonproteasomal proteolysis conceivably affects gene product levels above the level of transcription. Only two genes, MYOC and IGFBP2, showed significantly elevated expression after dexamethasone treatment in our study and the other three previously published reports of primary culture trabecular meshwork cell gene expression.