The mechanism of cytoplasmic incompatibility is conserved in Wolbachia-infected Aedes aegypti mosquitoes deployed for arbovirus control.

The rising interest and success in deploying inherited microorganisms and cytoplasmic incompatibility (CI) for vector control strategies necessitate an explanation of the CI mechanism. Wolbachia-induced CI manifests in the form of embryonic lethality when sperm from Wolbachia-bearing testes fertilize eggs from uninfected females. Embryos from infected females however survive to sustain the maternally inherited symbiont. Previously in Drosophila melanogaster flies, we demonstrated that CI modifies chromatin integrity in developing sperm to bestow the embryonic lethality. Here, we validate these findings using wMel-transinfected Aedes aegypti mosquitoes released to control vector-borne diseases. Once again, the prophage WO CI proteins, CifA and CifB, target male gametic nuclei to modify chromatin integrity via an aberrant histone-to-protamine transition. Cifs are not detected in the embryo, and thus elicit CI via the nucleoprotein modifications established pre-fertilization. The rescue protein CifA in oogenesis localizes to stem cell, nurse cell, and oocyte nuclei, as well as embryonic DNA during embryogenesis. Discovery of the nuclear targeting Cifs and altered histone-to-protamine transition in both Aedes aegypti mosquitoes and D. melanogaster flies affirm the Host Modification Model of CI is conserved across these host species. The study also newly uncovers the cell biology of Cif proteins in the ovaries, CifA localization in the embryos, and an impaired histone-to-protamine transition during spermiogenesis of any mosquito species. Overall, these sperm modification findings may enable future optimization of CI efficacy in vectors or pests that are refractory to Wolbachia transinfections.

The Hog1 MAPK substrate governs Candida glabrata-epithelial cell adhesion via the histone H2A variant.

CgHog1, terminal kinase of the high-osmolarity glycerol signalling pathway, orchestrates cellular response to multiple external stimuli including surplus-environmental iron in the human fungal pathogen Candida glabrata (Cg). However, CgHog1 substrates remain unidentified. Here, we show that CgHog1 adversely affects Cg adherence to host stomach and kidney epithelial cells in vitro, but promotes Cg survival in the iron-rich gastrointestinal tract niche. Further, CgHog1 interactome and in vitro phosphorylation analysis revealed CgSub2 (putative RNA helicase) to be a CgHog1 substrate, with CgSub2 also governing iron homeostasis and host adhesion. CgSub2 positively regulated EPA1 (encodes a major adhesin) expression and host adherence via its interactor CgHtz1 (histone H2A variant). Notably, both CgHog1 and surplus environmental iron had a negative impact on CgSub2-CgHtz1 interaction, with CgHTZ1 or CgSUB2 deletion reversing the elevated adherence of Cghog1Δ to epithelial cells. Finally, the surplus-extracellular iron led to CgHog1 activation, increased CgSub2 phosphorylation, elevated CgSub2-CgHta (canonical histone H2A) interaction, and EPA1 transcriptional activation, thereby underscoring the iron-responsive, CgHog1-induced exchange of histone partners of CgSub2. Altogether, our work mechanistically defines how CgHog1 couples Epa1 adhesin expression with iron abundance, and point towards specific chromatin composition modification programs that probably aid fungal pathogens align their adherence to iron-rich (gut) and iron-poor (blood) host niches.

Aspartyl proteases target host actin nucleator complex protein to limit epithelial innate immunity.

Epithelial-immune cell communication is pivotal to control microbial infections. We show that glycosylphosphatidylinositol-linked aspartyl proteases (Yapsins) of the human opportunistic pathogenic yeast Candida glabrata (Cg) thwart epithelial cell (EC)-neutrophil signalling by targeting the EC protein, Arpc1B (actin nucleator Arp2/3 complex subunit), which leads to actin disassembly and impeded IL-8 secretion by ECs. Further, the diminished IL-8 secretion inhibits neutrophil migration, and protects Cg from the neutrophil-mediated killing. CgYapsin-dependent Arpc1B degradation requires Arginine-142 in Arpc1B, and leads to reduced Arpc1B-p38 MAPK interaction and downregulated p38 signalling. Consistently, Arpc1B or p38 deletion promotes survival of the Cg aspartyl protease-deficient mutant in ECs. Importantly, kidneys of the protease-deficient mutant-infected mice display elevated immune cell infiltration and cytokine secretion, implicating CgYapsins in immune response suppression in vivo. Besides delineating Cg-EC interplay, our results uncover a novel target, Arpc1B, that pathogens attack to constrain the host signalling networks, and link Arpc1B mechanistically with p38 activation.

The Cif proteins from Wolbachia prophage WO modify sperm genome integrity to establish cytoplasmic incompatibility.

Inherited microorganisms can selfishly manipulate host reproduction to drive through populations. In Drosophila melanogaster, germline expression of the native Wolbachia prophage WO proteins CifA and CifB cause cytoplasmic incompatibility (CI) in which embryos from infected males and uninfected females suffer catastrophic mitotic defects and lethality; however, in infected females, CifA expression rescues the embryonic lethality and thus imparts a fitness advantage to the maternally transmitted Wolbachia. Despite widespread relevance to sex determination, evolution, and vector control, the mechanisms underlying when and how CI impairs male reproduction remain unknown and a topic of debate. Here, we use cytochemical, microscopic, and transgenic assays in D. melanogaster to demonstrate that CifA and CifB proteins of wMel localize to nuclear DNA throughout the process of spermatogenesis. Cif proteins cause abnormal histone retention in elongating spermatids and protamine deficiency in mature sperms that travel to the female reproductive tract with Cif proteins. Notably, protamine gene knockouts enhance wild-type CI. In ovaries, CifA localizes to germ cell nuclei and cytoplasm of early-stage egg chambers; however, Cifs are absent in late-stage oocytes and subsequently in fertilized embryos. Finally, CI and rescue are contingent upon a newly annotated CifA bipartite nuclear localization sequence. Together, our results strongly support the Host modification model of CI in which Cifs initially modify the paternal and maternal gametes to bestow CI-defining embryonic lethality and rescue.

Growth charts for weight and height of Indian children with Down syndrome.

Age and gender specific growth charts for Indian children with Down syndrome (DS) based on longitudinal data have not been published. To establish percentile growth charts for DS children inhabiting northwestern parts of India, body weight and length/height of 1125 (Male: 752, Female: 373) children with DS aged <1 month to 10 years, enrolled from the "Genetics Clinic" were measured at half yearly age intervals in the "Growth Clinic" of the Institute from August 1994 to November 2018. A total of 2089 observations were made on these children using standardized anthropometric techniques and instruments following a prospective mixed-longitudinal growth research design. Using the LMS method, age and sex-specific percentile growth charts (<1 month to 10 years) for weight, and length/ height were generated. Unpaired t-test was used to compare mean growth attainments of study children with those of DS patients representing other population groups as well as their normal Multicentre Growth Reference Study (MGRS and Indian Academy of Pediatrics (IAP) counterparts. The 50th percentile growth curves for both weight and length/height of Indian children with DS demonstrated a regular increase. As compared to their normal MGRS and Indian (IAP) counterparts, the children with DS had lower weight and height attainments. The boys and girls with Down syndrome showed short stature (height < 3rd centile) from the age of 1 year till 10 years and also became underweight beyond 5 years. As compared to their normal counterparts, children with Down syndrome exhibited compromised auxological attainments. The use of growth charts presented herein may be used to compare and monitor growth and nutritional status of Indian children with Down syndrome.

Unearthing diverse culturable fungal communities associated with Ophiocordyceps indica sp. nov. from Indian Western Himalaya.

Fungal communities colonizing Ophiocordyceps spp. plays a crucial ecological role in their natural habitat, contributing to infect the host larvae, and influencing their occurrence. Although associated fungi with the newly described Ophiocordyceps indica, from the Indian Western Himalaya remains unclear. Therefore, we untangled the culturable fungal communities associated with O. indica and soil adhered to it, collected from low-height areas of Himachal Pradesh, India. The study resulted in the identification of 111 fungal isolates representing 17 families, with maximum fungal isolates (36.03%) within Cordycipitaceae. Interestingly, a total of 24 genera were found associated with O. indica and adhered soil, of which 12 were common, 8 were exclusive to O. indica and 4 were only limited to soil. Additionally, the influence of soil physicochemical parameters on fungal diversity indices revealed a positive correlation with humidity and available nitrogen and a negative correlation with pH and available phosphorus. These findings provide insights into the culturable fungal diversity of O. indica and the soil adhering to it, thus can contribute to the understanding of host-microbial interactions. Furthermore, these associations can be explored as a source of bioactive metabolites to combat the unending industrial demands.

The yapsin family of aspartyl proteases regulate glucose homeostasis in Candida glabrata.

Invasive candidiasis poses a major healthcare threat. The human opportunistic fungal pathogen Candida glabrata, which causes mucosal and deep-seated infections, is armed with distinct virulence attributes, including a family of 11 glycosylphosphatidylinositol-linked aspartyl proteases, CgYapsins. Here, we have profiled total membrane proteomes of the C. glabrata wildtype and 11 proteases-deficient strain, Cgyps1-11Δ, by mass spectrometry analysis and uncovered a novel role for fungal yapsins in glucose sensing and homeostasis. Furthermore, through label-free quantitative membrane proteome analysis, we showed differential abundance of 42% of identified membrane proteins, with electron transport chain and glycolysis proteins displaying lower and higher abundance in Cgyps1-11Δ cells, compared with wildtype cells, respectively. We also demonstrated elevated glucose uptake and upregulation of genes that code for the low-glucose sensor CgSnf3, transcriptional regulators CgMig1 and CgRgt1, and hexose transporter CgHxt2/10 in the Cgyps1-11Δ mutant. We further elucidated a potential underlying mechanism through genetic and transcript measurement analysis under low- and high-glucose conditions and found CgSNF3 deletion to rescue high glucose uptake and attenuated growth of the Cgyps1-11Δ mutant in YPD medium, thereby linking CgYapsins with regulation of the CgSnf3-dependent low-glucose sensing pathway. Last, high ethanol production, diminished mitochondrial membrane potential, and elevated susceptibility to oxidative phosphorylation inhibitors point toward increased fermentative and decreased respiratory metabolism in the Cgyps1-11Δ mutant. Altogether, our findings revealed new possible glucose metabolism-regulatory roles for putative cell surface-associated CgYapsins and advanced our understanding of fungal carbohydrate homeostasis mechanisms.

The SET-domain protein CgSet4 negatively regulates antifungal drug resistance via the ergosterol biosynthesis transcriptional regulator CgUpc2a.

Invasive fungal infections, which pose a serious threat to human health, are increasingly associated with a high mortality rate and elevated health care costs, owing to rising resistance to current antifungals and emergence of multidrug-resistant fungal species. Candida glabrata is the second to fourth common cause of Candida bloodstream infections. Its high propensity to acquire resistance toward two mainstream drugs, azoles (inhibit ergosterol biosynthesis) and echinocandins (target cell wall), in clinical settings, and its inherent low azole susceptibility render antifungal therapy unsuccessful in many cases. Here, we demonstrate a pivotal role for the SET {suppressor of variegation 3 to 9 [Su(var)3-9], enhancer of zeste [E(z)], and trithorax (Trx)} domain-containing protein, CgSet4, in azole and echinocandin resistance via negative regulation of multidrug transporter-encoding and ergosterol biosynthesis (ERG) genes through the master transcriptional factors CgPdr1 and CgUpc2A, respectively. RNA-Seq analysis revealed that C. glabrata responds to caspofungin (CSP; echinocandin antifungal) stress by downregulation and upregulation of ERG and cell wall organization genes, respectively. Although CgSet4 acts as a repressor of the ergosterol biosynthesis pathway via CgUPC2A transcriptional downregulation, the CSP-induced ERG gene repression is not dependent on CgSet4, as CgSet4 showed diminished abundance on the CgUPC2A promoter in CSP-treated cells. Furthermore, we show a role for the last three enzymes of the ergosterol biosynthesis pathway, CgErg3, CgErg5, and CgErg4, in antifungal susceptibility and virulence in C. glabrata. Altogether, our results unveil the link between ergosterol biosynthesis and echinocandin resistance and have implications for combination antifungal therapy.

An aspartyl protease-mediated cleavage regulates structure and function of a flavodoxin-like protein and aids oxidative stress survival.

A family of eleven glycosylphosphatidylinositol-anchored aspartyl proteases, commonly referred to as CgYapsins, regulate a myriad of cellular processes in the pathogenic yeast Candida glabrata, but their protein targets are largely unknown. Here, using the immunoprecipitation-mass spectrometry approach, we identify the flavodoxin-like protein (Fld-LP), CgPst2, to be an interactor of one of the aspartyl protease CgYps1. We also report the presence of four Fld-LPs in C. glabrata, which are required for survival in kidneys in the murine model of systemic candidiasis. We further demonstrated that of four Fld-LPs, CgPst2 was solely required for menadione detoxification. CgPst2 was found to form homo-oligomers, and contribute to cellular NADH:quinone oxidoreductase activity. CgYps1 cleaved CgPst2 at the C-terminus, and this cleavage was pivotal to oligomerization, activity and function of CgPst2. The arginine-174 residue in CgPst2 was essential for CgYps1-mediated cleavage, with alanine substitution of the arginine-174 residue also leading to elevated activity and oligomerization of CgPst2. Finally, we demonstrate that menadione treatment led to increased CgPst2 and CgYps1 protein levels, diminished CgYps1-CgPst2 interaction, and enhanced CgPst2 cleavage and activity, thereby implicating CgYps1 in activating CgPst2. Altogether, our findings of proteolytic cleavage as a key regulatory determinant of CgPst2, which belongs to the family of highly conserved, electron-carrier flavodoxin-fold-containing proteins, constituting cellular oxidative stress defense system in diverse organisms, unveil a hidden regulatory layer of environmental stress response mechanisms.

Polymorphisms in ERCC1, ERCC4 and ERCC5 genes as biomarkers of susceptibility for pesticide-induced DNA damage in North-West Indian agricultural workers.

BACKGROUND: Occupational pesticides exposure has raised health concerns due to genotoxicity and accumulation of DNA damage. Polymorphisms in genes encoding enzymes involved in nucleotide excision repair (NER) may affect the individual's susceptibility to pesticide toxicity. METHODS: This study evaluates the association of excision repair cross complementation group 1 (ERCC1) (8092 C > A, 3'UTR, rs3212986) and ERCC1 (19007 C > T, Asn118Asn, rs11615), ERCC4 (1244 G > A, Arg415Gln, rs1800067) and ERCC5 (3507 G > C, Asp1104His, rs17655) polymorphisms with pesticide-induced DNA damage in North-West Indian agricultural workers. The study population comprised 225 agricultural workers exposed to pesticides and 225 non-exposed controls. RESULTS: Our study demonstrate that exposed workers carrying variant ERCC1 8092AA genotype showed higher total comet DNA migration (p = 0.015) as well as increased frequency of cells showing DNA migration (p = 0.027). Exposed agricultural workers with variant ERCC4 1244AA (415Gln/Gln) and ERCC5 3507CC (1104His/His) genotypes exhibited elevation in total comet DNA migration (p < 0.01). However, genotypes of ERCC1 19007 C > T (Asn118Asn) showed no association with total comet DNA migration (p = 0.963), frequency of cells showing DNA migration (p = 0.423) as well as mean tail length (p = 0.432). CONCLUSION: ERCC1, ERCC4 and ERCC5 polymorphisms influence DNA damage and can be used as biomarkers of susceptibility for pesticide-induced DNA damage in North-West Indian agricultural workers.

Histone H4 dosage modulates DNA damage response in the pathogenic yeast Candida glabrata via homologous recombination pathway.

Candida glabrata, a nosocomial fungal bloodstream pathogen, causes significant morbidity and mortality in hospitals worldwide. The ability to replicate in macrophages and survive a high level of oxidative stress contributes to its virulence in the mammalian host. However, the role of DNA repair and recombination mechanisms in its pathobiology is still being discovered. Here, we have characterized the response of C. glabrata to the methyl methanesulfonate (MMS)-induced DNA damage. We found that the MMS exposure triggered a significant downregulation of histone H4 transcript and protein levels, and that, the damaged DNA was repaired by the homologous recombination (HR) pathway. Consistently, the reduced H4 gene dosage was associated with increased HR frequency and elevated resistance to MMS. The genetic analysis found CgRad52, a DNA strand exchange-promoter protein of the HR system, to be essential for this MMS resistance. Further, the tandem-affinity purification and mass spectrometry analysis revealed a substantially smaller interactome of H4 in MMS-treated cells. Among 23 identified proteins, we found the WD40-repeat protein CgCmr1 to interact genetically and physically with H4, and regulate H4 levels, HR pathway and MMS stress survival. Controlling H4 levels tightly is therefore a regulatory mechanism to survive MMS stress in C. glabrata.

Development and validation of a novel core set of KASP markers for the traits improving grain yield and adaptability of rice under direct-seeded cultivation conditions.

The development and utilization of molecular-markers play an important role in genomics-assisted breeding during pyramiding of valuable genes. The aim of present study was to develop and validate a novel core-set of KASP (Kompetitive Allele-Specific PCR) markers associated with traits improving rice grain yield and adaptability under direct-seeded cultivation conditions. The 110 phenotypically validated KASP assays out of 171 designed KASP, include assays for biotic-resistance genes, anaerobic germination, root-traits, grain yield, lodging resistance and early-uniform emergence. The KASP assays were validated for their robustness and reliability at five different levels using diverse germplasm, segregating and advanced population, comparison with SSR markers and on F1s. The present research work will provide (i) breeding material in form of anticipated pre-direct-seeded adapted rice varieties (ii) single improved breeding line with many useful genes and (iii) KASP assay information for the useful QTL/genes providing grain yield and adaptability to rice under direct-seeded cultivation conditions.

Immunomodulatory effects of ß-defensin 2 on macrophages induced immuno-upregulation and their antitumor function in breast cancer.

BACKGROUND: Macrophages are mononuclear CD34+ antigen-presenting cells of defense mechanism and play dual roles in tumor burden. The immunomodulatory and their antitumor function of ß-defensin 2 is still unclear, despite the accumulating evidence of the response in infection. So, the aim of present study is to elucidate the role of ß-defensin 2 on the level of ROS, cytokines, chemokine expression in macrophages and antitumor function in breast cancer. METHOD: Swiss albino mice were used to harvest PEC macrophages and C127i breast cancer cells line for tumor model was used in this study. Macrophages were harvested and characterized by flow-cytometry using F4/80 and CD11c antibodies. MTT was performed to estimate cytotoxicity and dose optimization of ß-defensin 2. Oxidative stress was analyzed by H2O2 and NO estimation followed by iNOS quantified by q-PCR. Cytokines and chemokines estimation was done using q-PCR. Co-culture experiment was performed to study anti-tumor function using PI for cell cycle, Annexin -V and CFSE analysis for cell proliferation. RESULTS: PEC harvested macrophages were characterized by flow-cytometry using F4/80 and CD11c antibodies with the purity of 8% pure population of macrophages. It was found that 99% of cells viable at the maximum dose of 100 ng/ml of ß-defensin 2 in MTT. Levels of NO and H2O2 were found to be decreased in ß-defensin 2 as compared to control. Expression of cytokines of IFN-γ, IL-1α, TNF-α, TGF-ßwas found to be increased while IL-3 was decreased in ß-defensin 2 group as compared to control. Levels of chemokines CXCL-1, CXCL-5 and CCL5 increased in treated macrophages while CCL24 and CXCL-15 expression decreased. Adhesion receptor (CD32) and fusion receptor (CD204) were decreased in the ß-defensin 2 group as compared to control. Anti-tumor experiment was performed using co-culture experiment apoptosis (Annexin-V) was induced, cell cycle arrest in phage and cell proliferation of C127i cells was decreased. CONCLUSION: This is the first report of ß-defensin 2 modulates macrophage immunomodulatory and their antitumor function in breast cancer. ß-defensin 2 as a new therapeutic target for immunotherapy as an adjuvant in vaccines.

Role of chemokines in breast cancer.

Chemokines belong to a family of chemoattractant cytokines and are well known to have an essential role in various cancer aetiologies. Multiplesubsets of immune cells are recruited and enrolled into the tumor microenvironment through interactions between chemokines and their specific receptors. These populations and their interactions have a distinct impact on tumor growth, progression, and treatment outcomes. While it is clear that many chemokines and their cognate receptors can be detected in breast and other cancers, the role of each chemokine and receptor has yet to be determined. This review focuses on the main chemokines that play a crucial role in the tumor microenvironment, emphasizing breast cancer. We have also discussed the techniques used to identify the chemokines and their future implication in the early diagnosis of cancer. In-depth knowledge of chemokines and their role in breast cancer progression can provide specific targets for breast cancer biotherapy.

2Gs and plant architecture: breaking grain yield ceiling through breeding approaches for next wave of revolution in rice (Oryza sativa L.).

Rice is a principal food crop for more than half of the global population. Grain number and grain weight (2Gs) are the two complex traits controlled by several quantitative trait loci (QTLs) and are considered the most critical components for yield enhancement in rice. Novel molecular biology and QTL mapping strategies can be utilized in dissecting the complex genetic architecture of these traits. Discovering the valuable genes/QTLs associated with 2Gs traits hidden in the rice genome and utilizing them in breeding programs may bring a revolution in rice production. Furthermore, the positional cloning and functional characterization of identified genes and QTLs may aid in understanding the molecular mechanisms underlying the 2Gs traits. In addition, knowledge of modern genomic tools aids the understanding of the nature of plant and panicle architecture, which enhances their photosynthetic activity. Rice researchers continue to combine important yield component traits (including 2Gs for the yield ceiling) by utilizing modern breeding tools, such as marker-assisted selection (MAS), haplotype-based breeding, and allele mining. Physical co-localization of GW7 (for grain weight) and DEP2 (for grain number) genes present on chromosome 7 revealed the possibility of simultaneous introgression of these two genes, if desirable allelic variants were found in the single donor parent. This review article will reveal the genetic nature of 2Gs traits and use this knowledge to break the yield ceiling by using different breeding and biotechnological tools, which will sustain the world's food requirements.

Molecular mapping and transfer of a novel brown planthopper resistance gene bph42 from Oryza rufipogon (Griff.) To cultivated rice (Oryza sativa L.).

BACKGROUND: Brown planthopper (BPH), Nilaparvata lugens (Stål), is one of the most destructive pests of rice accounting for 52% of annual yield loss. The breakdown of resistance against known BPH biotypes necessitates the identification and deployment of new genes from diverse sources. The current study aimed at mapping and transfer of a novel BPH resistance gene from the wild species of rice O. rufipogon accession CR100441 to the elite rice cultivar against BPH biotype 4. METHODS AND RESULTS: The phenotypic screening against BPH biotype 4 was conducted using the standard seedbox screening technique (SSST). Inheritance study using damage score caused by BPH infestation at the seedling stage indicated the presence of a single major recessive gene with the segregation ratio of susceptible to resistant plants in 3:1 (210:66, χ2c = 0.17 ≤ χ20.05,1 = 3.84). The genotyping of the mapping population was done using polymorphic microsatellite markers between PR122 and O.rufipogon acc.CR100441 spanning all the 12 chromosomes of rice. A total of 537 SSR markers were used to map a BPH resistance gene (designated as bph42) on the short arm of chromosome 4 between RM16282 and RM6659. QTL analysis identified a peak marker RM16335 contributing 29% of the phenotypic variance at 40.76 LOD. CONCLUSIONS: The identified marker co-segregates with the bph42 and hence could be efficiently used for marker-assisted selection (MAS) for the transfer of resistance into elite rice cultivars. The introgression lines with higher yield and BPH resistance were identified and are under advanced yield trails for further varietal release.

Detection of ocular hypertelorism among Indian children.

Background & objectives: Ocular hypertelorism constitutes an important component of many clinical syndromes. It is typically recommended to use inter-pupillary distance (IPD) for objective evaluation of ocular hypo/hypertelorism. Barring infancy, there is a scarcity of data on this anthropometric parameter relating to the ocular apparatus. This study aims to study auxological dynamics of IPD in children of Indian origin. Methods: A total of 3622 ( 2239 males and, 1383 females) normal, healthy Indian children of North-western origin, aged one month to 14 yr comprised the sample for this study. Inner and outer-canthal distance were measured using standardized anthropometric techniques. None of the children who participated in this study had craniofacial dysmorphism or any body deformity. Mean (standard deviation SD) and percentiles were calculated for IPD in male and female subjects at different age levels. Results: IPD increased from 4.68±0.21 to 6.19±0.36 cm in males and from 4.59±0.26 to 6.08±0.25 cm in females between one month and 14 yr of age. Boys in general, possessed larger IPD than girls, however, the gender differences became significant (P≤0.05) at 10, 11, 16-18 and 22-24 months, respectively, and five and 10 yr of age, respectively. Interpretation & conclusions: The results of this study suggest that the patients having IPD less than the 3rd percentile should be treated as cases of hypotelorism while, those exceeding 97th percentile as cases of hypertelorism. The use of percentile grids presented for IPD may be used to detect ocular hypotelorism and hypertelorism in male and female children to corroborate diagnosis of different syndromes.

Efficacy of Microneedling With 35% Glycolic Acid Peels Versus Microneedling With 15% Trichloroacetic Acid Peels in Treatment of Atrophic Acne Scars: A Randomized Controlled Trial.

BACKGROUND: Combination of microneedling and chemical peeling is a simple cost-effective treatment for acne scars. OBJECTIVE: To compare efficacy and safety of combining microneedling with 35% glycolic acid (GA) peel versus microneedling with 15% trichloroacetic acid (TCA) peel in facial atrophic acne scars. METHODS: Forty acne scars patients were randomly divided into 2 groups of 20 each. Patients underwent microneedling followed by 35% GA peeling in Group 1 and 15% TCA peeling in Group 2 at 2 weekly intervals. Improvement was graded by Goodman and Baron's qualitative and quantitative global acne scar grading systems, physician's global assessment, and visual analogue scale (VAS). Skin texture was graded by VAS. RESULTS: On comparing qualitative and quantitative acne scar grading within groups, there was significant difference from the baseline. When the two groups were compared for quantitative and qualitative acne scar grading, the difference was statistically not significant at the end of therapy. In VAS, greater number of patients assessed response as excellent and good in Group 1 than in Group 2 indicating better skin texture improvement in Group 1. CONCLUSION: Both combinations were equally efficacious in treating acne scars. Glycolic acid peel delivered additional advantage of improvement in skin texture.

Scrutinising the role of simvastatin in a patient of Pachyonychia Congenita with KRT6A gene mutation.

A 25-year-old male patient presented with palmoplantar keratoderma, dystrophic nails, severe plantar pain and oral leukokeratosis since birth. On genetic analysis, a heterozygous KRT6A gene missense mutation (c.1381G > A, p.Glu461Lys in exon 7) was identified by next-generation sequencing technology, consistent with pachyonychia congenita 6a. Oral simvastatin 40 mg was started once daily, and after 16 weeks of therapy, excellent improvement was noted in palmoplantar keratoderma and plantar pain. The maximum thickness of his foot callosity reduced by 4 mm on ultrasonography, and the Dermatology Life Quality Index score dropped significantly by eight points. These benefits may be attributed to inhibition of KRT6A gene expression, modulation of autophagy and mitophagy and Keap1-Nrf2 signalling activation; the latter two mechanisms of statins previously undiscussed in the context of pachyonychia congenita. Simvastatin and other statins are pathogenesis-targeted, disease-modifying therapy in pachyonychia congenita, therefore qualifying as a promising treatment avenue and warranting further clinical trials.

Mucormycosis in COVID-19 pandemic and its neurovascular spread.

PURPOSE: Rhinocerebral mucormycosis is a rapidly progressive angioinvasive fungal infection commonly seen in diabetics. In the COVID-19 pandemic we have witnessed a sudden surge in these cases. We aimed to evaluate the disease presentation, patterns of spread, and any association with the COVID-19 virus. METHODS: This prospective study was conducted on mucormycosis patients operated between March and July 2021. The diagnosis was confirmed either on KOH staining, fungal culture or histopathological examination. RESULTS: Thirty one cases (21 males, 10 females) with a mean age of 53.3 years were included, of which 9 (29.1%) were COVID positive on presentation, 17 (54.8%) were post-COVID, while 5 (16.1%) had radiological evidence of COVID sequelae. Most common symptoms were cheek numbness (87.1%), headache (83.9%), visual disturbances (77.4%), and palate involvement (58.1%). Blackening of turbinates was uncommon (22.6%). Ethmoid sinus was involved in all patients. Pterygopalatine fossa involvement was present in 77.4%, and was accurately diagnosed on contrast enhanced MRI scan. There were 8 (25.8%) deaths, while the remaining are discharged or under treatment. CONCLUSION: An increase in the incidence of mucormycosis in the COVID-19 pandemic is probably due to a compromise in host immunity along with a synergistic effect in thrombotic microangiopathy. Spread of infection to the soft tissues of the infratemporal fossa, orbit or palate occur via neurovascular structures rather than by bone erosion. The pterygopalatine fossa is involved in most individuals.