Insights into the role of complement regulatory proteins in HPV mediated cervical carcinogenesis.

The persistent infection of high-risk Human papillomavirus (HR-HPV) induced cervical cancer remains a challenge in women worldwide including India. Recent advances in cancer research have paved the way for advanced cancer treatment modalities including immunotherapy by manipulating the function or number of cytotoxic T cells. It is well established that anaphylatoxins like C3a and C5a of complement system influence tumor growth by evading apoptosis leading to progression of cancer. The role of the complement system, particularly the complement regulatory proteins (CRPs) which are important determinants of immune response play a crucial role in carcinogenesis. In a tumor microenvironment (TME) assisted suppression of immune effector cells may be achieved through CRPs. However, recent advances in pharmacogenomics including drug designing and combination of these approaches have provided a holistic understanding of signaling pathways and their crosstalk, to regulate cellular communications.This review describes the role of complement system; particularly CRPs in HPV induced cervical carcinogenesis which may be used for designing anti- HPV or cervical cancer therapeutics.

Psychological distress and moral injury to oncologists and their patients during COVID-19 pandemic.

The impact of the COVID-19 pandemic on healthcare systems has been unprecedented, and the psychological effects on cancer patients and health care professionals are likely to be significant and long-lasting. The traditional methods of face-to-face health care interactions have been replaced by virtual consultations to reduce exposure to COVID-19 infection. This has put the healthcare professional under tremendous psychological pressure and led to considerable anxiety and distress among cancer patients. Treatment decisions have had to be adjusted to account for a healthcare system that has been temporarily consumed by the care of people with COVID-19, and this has put cancer patients at risk of inferior outcomes. This has had the potential to cause moral injury and psychological distress to health care professionals as well as patients, who have had to deal with a range of stressors due to the uncertainty, sense of loss of control, reduced accessibility to medications and social support, changes to personal circumstances (e.g. financial pressures) and fear of death due to COVID-19 infection. Long term consequences also include post-traumatic responses and complex grief reactions. Cancer services in particular should gear themselves to recognize and monitor these effects and allocate adequate resources to combat them in the months and years to come.

Review of Vitamin B12 deficiency in pregnancy: a diagnosis not to miss as veganism and vegetarianism become more prevalent.

Vegetarianism and veganism are increasingly popular. The Food Standards Agency, biennial Food and You Survey of adults aged 16 years and over living in the UK, found that between 2012 and 2018 the proportion of people who reported never consuming dairy products had increased from 2% to 5%. However, veganism risks development of vitamin B12 deficiency as it is not available from plant sources. Moreover, its impact may be slow to be detected because body stores of vitamin B12 can last years. There is currently no published guidance on antenatal diagnosis and management of vitamin B12 deficiency. This paper reviews the metabolism, diagnosis and treatment of vitamin B12 in pregnancy. It concludes that national screening policymakers should consider introducing screening for B12 deficiency into the Antenatal and Newborn Screening Programmes for mothers and their infants if at risk of vitamin B12 deficiency. In the interim, national policy should be developed for prophylactic vitamin B12 supplementation in high-risk groups around the time of pregnancy.

Contribution of TGFß1 codon 10 polymorphism to high myopia in an ethnic Kashmiri population from India.

This study looks at novel variants of the TGFß1 gene and their potential association with high myopia in an ethnic population from Kashmir, India. Allele frequencies of 247 Kashmiri subjects (from India) with high myopia and 176 ethnically matched healthy controls were tested for Hardy-Weinberg disequilibrium. The genotype and allele frequencies were evaluated using chi-square or Fisher's exact tests. One of the three SNPs in codon 10 showed a significant difference between patients and control subjects (rs1982073: p genotype = 0.003, p allele = 0.001). There were no statistically significant differences between patients and control subjects for the other two SNPs, rs1800471 at codon 25 and a novel variant at codon 52. SNP rs1982073, substituting proline with leucine, appeared to be significantly associated with high myopia (p < 0.05). In silico predictions show that substitutions are likely to have an impact on the structure and functional properties of the protein, making it imperative to understand their functional consequences in relation to high myopia.

Unusual CD34 positivity in acute myeloid leukaemia with myelodysplasia-related changes with megakaryoblastic differentiation.

Acute megakaryoblastic leukaemia is a rare entity with distinct immunophenotype profile and cytogenetic lesions. Herein, we report a case of acute myeloid leukaemia with myelodysplastic-related changes with megakaryoblastic differentiation in absence of recurrent genomic lesions such as t(1;22), inv(3) and t(3;3). One of the peculiarities of this case is the positivity of CD34+ within the abnormal megakaryoblasts; CD61 immunohistochemistry highlights the heavily infiltration of bone marrow from abnormal megakaryoblasts.

MYP2 locus genes: Sequence variations, genetic association studies and haplotypic association in patients with High Myopia.

High Myopia (HM) is a common complex-trait eye disorder. There is essential evidence that genetic factors play a significant role in the development of nonsyndromic high myopia. Identification of susceptibility genes of high myopia will shed light on the pathophysiological mechanism underlying their genesis. This was a case control study examining the prospect of association of DLGAP1, EMILIN2 & MYOM1 genes on MYP2 locus in purely ethnic (Kashmiri) population representing a homogeneous cohort. Genomic DNA was extracted using phenol chloroform and salting out method. Extracted DNA was genotyped for polymorphic variations in MYOM1, EMILIN2 and DLGAP1 genes involving Sanger di-deoxy method. Allele frequencies were tested for Hardy-Weinberg disequilibrium in 224 cases and compared with 220 emmetropic controls. In DLGAP1, documented single nucleotide polymorphism (SNP); Pro517Pro was observed. A previously reported Asn451Asn SNP was observed in EMILIN2. MYOM1 showed five polymorphic variations; two in coding region (Gly333Gly & Gly341Ala) and three intronic (c.1022+23, G>A; c.3418+44 G>T & c.3418+65; C>G). All of the elucidated SNPs were having statistical significant role in increasing or decreasing the risk of disease. Although not statistically significant, a novel Glu507Lys SNP was observed in DLGAP1 (P>0.05). In silico predictions showed MYOM1 Gly341Ala to be benign & tolerated substitution while as DLGAP1 Glu507Lys to be possibly damaging substitution. The studied SNPs followed Over-Dominant, Recessive and Co-Dominant mode of inheritance with specific haplotypes associated with the disease. Our study reveals the involvement of MYP2 locus candidate gene polymorphism in the pathogenesis of HM.

A novel G26A variation in 5' half of TGIF1 gene associates with high myopia in ethnic Kashmiri population from India.

This study aims to look at novel variations in TGIF1 gene and explores their potential association with high myopia in an ethnic population from Kashmir (India). Genomic DNA was genotyped for polymorphic variations, and allele frequencies were tested for the Hardy-Weinberg disequilibrium in 240 ethnic Kashmiri cases with high myopia with a spherical equivalent of >-6 diopters (D) and compared with emmetropic controls with spherical equivalent within -0.5D in one or both eyes represented by a sample size of 228. In this study, we found a novel sequence variation G26A (GAT to AAT) in 5' half of TGIF1 gene (p. aspartic acid >asparagine) at a frequency of 62% (148/240, P ≤ 0.0001). Variation appears to associate with high myopia significantly (P ≤ 0.001) as it happens to be present only in high myopia affected individuals. Further, it shows statistical significance for its association with gender and the degree of myopia (P ≤ 0.05). In addition, in silico predictions show that variation likely has an impact on the structure and functional properties of the protein. The assessment of the I-TASSER protein structure showed higher energy for a wild-type protein (-5820.186 kJ/mol) as compared to mutant protein (-6595.593 kJ/mol).

Bacterial and fungal profile of corneal ulcers--a prospective study.

Corneal ulceration continues to be one of the most important causes of ocular morbidity and blindness worldwide. Between April 1999 and May 2001, 80 patients with corneal ulceration were examined to find the causative microorganisms, the sensitivity pattern of bacterial isolates to antibiotics, the predisposing factorsfor ulcerative keratitis and the comparison between culture and gram staining results. Corneal ulceration was seen more in males than females, predominantly in farmers (61.25%) and trauma was the commonest predisposing factor, the agents being mainly organic agricultural materials. Of the 80 corneal ulcers, 32(40%) yielded pure bacterial growth while fungal growth was seen in 10(12.5%). Streptococcus pneumoniae was the commonest bacterium while Aspergillus fumigatus and Fusarium species were the commonest fungi isolated. Most of the bacterial isolates were sensitive to chloramphenicol and tetracycline followed by the quinolones. The overall sensitivity and specificity of Gram staining as compared to culture was 57.14% and 94.7% respectively.

Success rate of probing for congenital nasolacrimal duct obstruction at various ages.

PURPOSE: To determine the success rate of probing for congenital nasolacrimal duct obstruction (CNLDO) in various age groups. METHODS: One hundred children (118 eyes) aged 4 to 48 months diagnosed with CNLDO were included and divided into 6 groups; group 1: infants 4-6 months of age, group 2: infants from 7 to 12 months, group 3: toddlers 13-18 months of age, group 4: older toddlers 19-24 months old, group 5: children from 25 to 36 months, and group 6: children 37-48 months of age. Probing was performed under general anesthesia in all subjects. All patients were followed at regular intervals up to 6 months postoperatively. Successful probing was documented as complete remission of symptoms 2 weeks following the procedure. RESULTS: The success rate of probing was 100% (2 eyes) in group 1, 94% (47 eyes) in group 2, 84.4% (27 eyes) in group 3, 83.3% (15 eyes) in group 4, 61.5% (8 eyes) in group 5 and 33.3% (1 eye) in group 6; the overall success rate was 84.7% (100 eyes). The majority of eyes, 87.3% (103 eyes), had membranous obstruction while 12.7% (15 eyes) had firm obstruction. The success rate was 92.2% (95 eyes) in eyes with membranous obstruction and 33.3% (5 eyes) in those with firm obstruction. CONCLUSION: Probing of the nasolacrimal duct under general anesthesia is a safe and viable option as a primary treatment modality for CNLDO. The success rate decreases with increasing age; membranous obstruction resolves in the majority of cases whereas firm obstruction has a poorer outcome.