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Introduction: Mucoid degeneration of the anterior cruciate ligament (MDACL) is a poorly understood entity. The collection of mucinous material in the substance of anterior cruciate ligament (ACL) produces pain and thus limits motion in the knee. This study involves clinic-radiological presentation of patients with mucoid ACL, arthroscopic de-bulking of ACL and outcomes. Materials and Methods: Between September 2021 and October 2022, 24 patients were diagnosed with MDACL. All cases were examined clinically followed by magnetic resonance imaging (MRI) then confirmed by arthroscopy findings and then were sent for histopathology reporting. Clinical data, including pain location, terminal flexion or extension pain, range of motion, Lysholm knee score, and International Knee Documentation Committee score, were assessed pre- and postoperatively. MRI showing an increased signal of the ACL in T1-and T2-weighted images was reported as mucoid degeneration of the ACL by the radiologist. Upon arthroscopy, the ACL had a homogenous, bulbous, hypertrophied, and taut appearance occupying most of the intercondylar notch space. Debulking of the ACL was performed by excision of the degenerated mucoid tissue, leaving behind as much of the intact ACL as possible, and notchplasty helped prevent impingement of the ACL against the roof and lateral wall. Unfortunately, in 4 (16.67%) patients, we had to reconstruct the ligament due to the ACL insufficiency to stabilize the knee. Results: Thirteen patients were males (54.17%), and eleven (45.83%) patients were females, with a mean age of 36.7 years for males (range 19–63 years) and 41.7 years for females (range 28–73 years). All patients had pain in deep flexion, with 70.8% (n = 1 7) reporting trivial trauma before the onset of symptoms. On terminal flexion/extension, pain relief was obtained in 19 of 20 knees, ranging from good to excellent. Stability tests for ACL showed a firm endpoint in all. GNRB arthrometer examination revealed a tibial translation comparable to the noninvolved side, and 85% (n = 20) showed good to excellent subjective satisfaction. Conclusions: Prior knowledge of the condition with a high suspicion index and careful MRI interpretation can establish the diagnosis preoperatively. They respond well to a judicious arthroscopic debulking of the ACL with or without notchplasty, improving patient satisfaction and function without causing clinical instability in daily activities. However, young patients should be forewarned about the risk of instability, and the necessity of ACL reconstruction in the future.

Introduction: Dermoscopy of mucosa is known as mucoscopy. Mucoscopy can aid in delineating minute aspects of mucosal lesions and will guide in the differentiation of similar-looking lesions. To date, there are only a few studies on mucoscopy of genital dermatoses especially from India. Aim and Objectives: The study aims to describe mucoscopic features and correlate histopathologically in various genital mucosal diseases. Materials and Methods: The study was conducted in a tertiary care center in Central India after IHEC approval between October 2020 and April 2022, and the sampling technique was based on a convenience purposive method. Any genital mucosal diseases were included in patients above 18 years of age. Sexually transmitted diseases in general were excluded, however, warts and molluscum contagiosum were included. All patients fulfilling the inclusion criteria were examined after proper informed consent, and the clinical images were photographed using iPhone 11. Dermoscopic images were taken using a DermLite DL4 dermoscope in polarized mode at 10X magnification. Results: A total of 206 patients were recruited, and mucoscopy features were analyzed. Dermoscopic findings of physiological conditions such as vestibular papillomatosis, pearly penile papules, and Fordyce spots were evaluated. Inflammatory conditions such as lichen planus, pemphigus, and psoriasis were analyzed. Mucoscopy of lichen sclerosus showed white structureless areas (100%), follicular plugs (35%), as well as dotted and linear vessels (80%). Circinate balanitis revealed regular red dotted vessels (100%), coalescing pustules in annular and polycyclic patterns (90%). Squamous cell carcinoma of the penis showed ulceration, serpentine, looped vessels, white structureless area, and yellow-brown crust in a pink background. Limitations: In our study, because of the inclusion of various diseases, sample size was inadequate, biopsies were not performed in all cases, and variations in mucoscopic features in patients who are already on therapy could not be assessed. Haziness while capturing pictures because of mist formation was hindering the quality of pictures. As patients with premalignant and malignant cases were less, the predicting features for malignant transformation or pathognomoniic signs could not be assessed. Conclusion: Various dermoscopies have been studied extensively, but the mucoscopy is still a gray area. The results of this study revealed the dermoscopic features of various genital disorders and histopathological correlation in few cases. However, biopsy was not performed in all mucosal disorders; hence, conclusive correlation could not be extrapolated.

Date palm (Phoenix dactylifera L.) cultivation in the Arabian Peninsula is crucial for regional agriculture and global markets. The Arabian Peninsula is dominant in date production, contributing approximately 34 % of the global output. Recent advancements in agricultural technologies have improved fruit yield and quality, expanding date palm cultivation globally. However, sustainability challenges persist due to various abiotic stresses, such as salinity, temperature extremes, drought, soil factors, and biotic stresses, including diseases and pests. This review examines key environmental factors affecting date palm cultivation, with a focus on soil salinity, water scarcity, and climate change-related stresses. The genetic diversity among date palm varieties is emphasized, highlighting the need for breeding programs aimed at improving stress tolerance and yield. Biotechnological advancements, such as genetic transformation and genome editing, are discussed for their potential to enhance crop resilience and productivity. Additionally, remote sensing techniques are explored for their application in precision agriculture, particularly in the mapping and monitoring of date palm health and soil conditions. The significant role of artificial intelligence in accurately mapping date palm trees using multi-platform remotely sensed data is also reviewed, illustrating its potential to enhance geospatial databases and support sustainable management practices. The review concludes with recommendations for optimizing cultivar selection and management strategies tailored to local conditions, emphasizing the need for ongoing research to advance date palm cultivation on a global scale.

Introduction: Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are primary scarring alopecias that few authors consider the same entity, and some consider them different. Objective: We describe and summarize the trichoscopy features of both conditions. Methods: We performed extensive literature search using the PubMed and Google Scholar databases. The Chi-square test was applied to for calculating the proportions of dermoscopic features in LPP and FFA. P- values less than 0.05 were considered statistically significant. Results: Out of 60 articles, 33 (16 LPP, 17 FFA) were considered for quantitative analysis due to availability in English literature with full text. We found that peripilar cylindrical casts and perifollicular redness with arborizing vessels were predominant features suggesting early LPP. In contrast, yellow dots, perifollicular erythema, and scattered pigmentation suggested active FFA. Shiny white area was seen in both groups in the inactive stages. The target arrangement of blue-grey dots, milky-red areas, and irregularly arranged white fibrotic dots were seen in late LPP, and black dots, lonely hairs, and loss of vellus hairs were detected in the later stages of FFA. Features such as blue-grey structureless areas, blue-white veil, and variability in morphologies of hair shafts were nonspecific. Conclusion: This article provides a comprehensive literature review, correlating dermoscopic features with histopathological findings and the similarities, differences, and peculiarities of LPP and FFA.

Abstract Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells. Human induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division with an inherent propensity to differentiate into neurons. These phenotypes result from misalignment of the mitotic spindle in apical neural progenitors. Cells lacking DENND5A orient away from the proliferative apical domain surrounding the ventricles, biasing daughter cells towards a more fate-committed state, ultimately shortening the period of neurogenesis. This study provides a mechanism for DENND5A-related DEE that may be generalizable to other developmental conditions and provides variant-specific clinical information for physicians and families.

Abstract Background Current clinical diagnosis pathway for lysosomal storage disorders (LSDs) involves sequential biochemical enzymatic tests followed by DNA sequencing, which is iterative, has low diagnostic yield and is costly due to overlapping clinical presentations. Here, we describe a novel low-cost and high-throughput sequencing assay using single-molecule molecular inversion probes (smMIPs) to screen for causative single nucleotide variants (SNVs) and copy number variants (CNVs) in genes associated with 29 common LSDs in India. Results 903 smMIPs were designed to target exon and exon–intron boundaries of targeted genes (n = 23; 53.7 kb of the human genome) and were equimolarly pooled to create a sequencing library. After extensive validation in a cohort of 50 patients, we screened 300 patients with either biochemical diagnosis (n = 187) or clinical suspicion (n = 113) of LSDs. A diagnostic yield of 83.4% was observed in patients with prior biochemical diagnosis of LSD. Furthermore, diagnostic yield of 73.9% (n = 54/73) was observed in patients with high clinical suspicion of LSD in contrast with 2.4% (n = 1/40) in patients with low clinical suspicion of LSD. In addition to detecting SNVs, the assay could detect single and multi-exon copy number variants with high confidence. Critically, Niemann-Pick disease type C and neuronal ceroid lipofuscinosis-6 diseases for which biochemical testing is unavailable, could be diagnosed using our assay. Lastly, we observed a non-inferior performance of the assay in DNA extracted from dried blood spots in comparison with whole blood. Conclusion We developed a flexible and scalable assay to reliably detect genetic causes of 29 common LSDs in India. The assay consolidates the detection of multiple variant types in multiple sample types while having improved diagnostic yield at same or lower cost compared to current clinical paradigm.

Abstract Objective Literature on the genotypic spectrum of Infantile Epileptic Spasms Syndrome (IESS) in children is scarce in developing countries. This multicentre collaboration evaluated the genotypic and phenotypic landscape of genetic IESS in Indian children. Methods Between January 2021 and June 2022, this cross‐sectional study was conducted at six centers in India. Children with genetically confirmed IESS, without definite structural‐genetic and structural‐metabolic etiology, were recruited and underwent detailed in‐person assessment for phenotypic characterization. The multicentric data on the genotypic and phenotypic characteristics of genetic IESS were collated and analyzed. Results Of 124 probands (60% boys, history of consanguinity in 15%) with genetic IESS, 105 had single gene disorders (104 nuclear and one mitochondrial), including one with concurrent triple repeat disorder (fragile X syndrome), and 19 had chromosomal disorders. Of 105 single gene disorders, 51 individual genes (92 variants including 25 novel) were identified. Nearly 85% of children with monogenic nuclear disorders had autosomal inheritance (dominant‐55.2%, recessive‐14.2%), while the rest had X‐linked inheritance. Underlying chromosomal disorders included trisomy 21 (n = 14), Xq28 duplication (n = 2), and others (n = 3). Trisomy 21 (n = 14), ALDH7A1 (n = 10), SCN2A (n = 7), CDKL5 (n = 6), ALG13 (n = 5), KCNQ2 (n = 4), STXBP1 (n = 4), SCN1A (n = 4), NTRK2 (n = 4), and WWOX (n = 4) were the dominant single gene causes of genetic IESS. The median age at the onset of epileptic spasms (ES) and establishment of genetic diagnosis was 5 and 12 months, respectively. Pre‐existing developmental delay (94.3%), early age at onset of ES (

Abstract Bi‐allelic variants in peroxiredoxin 3 (PRDX3) have only recently been associated with autosomal recessive spinocerebellar ataxia characterized by early onset slowly progressive cerebellar ataxia, variably associated with hyperkinetic and hypokinetic features, accompanied by cerebellar atrophy and occasional olivary and brainstem involvement. Herein, we describe a further simplex case carrying a reported PRDX3 variant as well as two additional cases with novel variants. We report the first Brazilian patient with SCAR32, replicating the pathogenic status of a known variant. All presented cases from the Brazilian and Indian populations expand the phenotypic spectrum of the disease by displaying prominent neuroradiological findings. SCAR32, although rare, should be included in the differential diagnosis of sporadic or recessive childhood and adolescent‐onset pure and complex cerebellar ataxia.

Scrub typhus is an established cause of acute encephalitis syndrome (AES) in northern states of India. We systematically investigated 376 children with AES in southern India, using a stepwise diagnostic strategy for the causative agent of scrub typhus, Orientia tsutsugamushi, including IgM and PCR testing of blood and cerebrospinal fluid (CSF) to grade its association with AES. We diagnosed scrub typhus in 87 (23%) children; of those, association with AES was confirmed in 16 (18%) cases, probable in 55 (63%), and possible in 16 (18%). IgM detection in CSF had a sensitivity of 93% and specificity of 82% compared with PCR. Our findings suggest scrub typhus as an emerging common treatable cause of AES in children in southern India and highlight the importance of routine testing for scrub typhus in diagnostic algorithms. Our results also suggest the potential promise of IgM screening of CSF for diagnosis of AES resulting from scrub typhus.

Microplastics (MPs) are an issue of prime environmental concern globally. The abundance of MP particles in the informal open solid waste landfill soil was evaluated showing 180–1120 MP particles per kg of soil. Moisture content (MC), electrical conductivity (EC) and pH of the MP-contaminated soil compared to the baseline showed 2.96% MC, 187–441 μS/cm EC and 6.94 pH. Morphology of extracted MPs in SEM showed particle fragmentation as film fragments (13.7%), fragments (56.1%), fibres (26.4%) and foam (3.8%). EDS results showed Carbon 71.8% and 24.5% oxygen with traces of Na, Al, Si and Cl−. FTIR of field obtained MPs identified were polyethylene and polypropylene. The association of MP particles with COD and chloride was discovered. MP particles of Low-density Polyethylene of size of 1 mm × 1 mm and thickness 25 μm up to 20 numbers showed no effect adding to the COD values. The COD values increased with increase in MP particle numbers. Similarly, chloride associations with MP particles showed an increase in MP particles reducing chloride values by 31% in landfill runoff water. It is interpreted that MP particle disintegration into nano-sized plastics (NPs) in the soil/runoff water can greatly increase the COD values and impair the salt mass balance. HIGHLIGHTS Municipal urban informal landfill soil was evaluated for abundance of MP particles.; The associated environmental parameters like pH, EC, TDS were evaluated.; SEM, EDS, FT-IR were used to understand the analytics and morphology of the extracted MPs.; MP associations with COD and chloride are established for the first time.;

Mitochondrial disorders are a group of metabolic disorders with variable presentation and usually affect organs with high energy requirements like the brain, eye, and heart. Seventeen-month-old girl child presented with right hemiparesis and regression of milestones following chicken pox. Investigations showed elevated lactate, white matter signal changes in both periventricular and subcortical white matter with frontal predominance in the MRI of the brain, cardiomyopathy in the echocardiography, with complex I deficiency in respiratory enzyme assay in the muscle biopsy. A homozygous missense variant c.304C>T (p. Arg102Cys) in exon 5 of NDUFS8 gene (chr11:67800682C>T; NM_002496.4) was detected on whole exome sequencing with positive parental Sanger for the same gene. The child was started on a mitochondrial cocktail, ramipril, and frusemide. Mitochondrial complex deficiency should be considered in cases with stroke-like episodes, and predominant white matter involvement on imaging mimicking classical genetic leukodystrophy like Alexander disease.

Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome.

Malate dehydrogenases (MDH) serve a critical role in maintaining equilibrium of the NAD+/NADH ratio between the mitochondria and cytosol through the catalysis of the oxidation of L-malate to oxaloacetate in a reversible, NADH-dependent manner. MDH2 encodes the mitochondrial isoform, which is integral to the tricarboxylic acid cycle and thus energy homeostasis. Recently, five patients harboring compound heterozygous MDH2 variants have been described, three with early-onset epileptic encephalopathy, one with a stroke-like episode, and one with dilated cardiomyopathy. Here, we describe an additional seven patients with biallelic variants in MDH2, the largest and most neurodevelopmentally and ethnically diverse cohort to-date, including homozygous variants, a sibling pair, non-European patients, and an adult. From these patients, we learn that MDH2 deficiency results in a biochemical signature including elevations of plasma lactate and the lactate:pyruvate ratio with urinary excretion of malate. It also results in a recognizable constellation of neuroimaging findings of anterior-predominant cerebral atrophy, subependymal cysts with ventricular septations. We also recognize MDH2 deficiency as a cause of Leigh syndrome. Taken with existing patient reports, we conclude that MDH2 deficiency is an emerging and likely under-recognized cause of infantile epileptic encephalopathy and provide a framework for medical evaluation of patients identified with biallelic MDH2 variants.

Background: Canavan disease (CD) is an autosomal recessively inherited leukodystrophy. It affects one in 6,400 to 13,500 people in the Jewish population. However, prevalence and presentation of the disease in India is largely unknown; hence, we are reporting this series. Methods: This is a retrospective chart review in a tertiary care hospital from January 2015 to March 2020. CD was confirmed by elevated N- acetyl aspartate (NAA) levels in urinary gas chromatography and mass spectrometry (GCMS)/increased NAA peak in magnetic resonance spectroscopy (MRS) and/or detection of mutations. The data was extracted in a predesigned proforma and analyzed. Results: We had 12 children with mean age at presentation being 6.8 months (range 3 months to 10 months.). Males were more commonly affected (83.3%, n = 10). Ten children (83.3%) were born out of consanguineous parentage. All of them had visual impairment and pyramidal signs. Seizures were noted in five (42%) children. Normal head size in three (25%) and microcephaly in two (16.66%) cases were noted. Magnetic resonance imaging (MRI) revealed signal changes with bilateral symmetric T2W white matter (WM) hyperintensities in subcortical U fibers in all cases. MRS was done in ten children, all of which showed increased NAA peak. Increased level of NAA in urinary GCMS was noted in six out of eight children. Six cases had homozygous pathogenic variants in ASPA gene. Antenatal diagnosis helped in prevention of recurrence in three families. Conclusion: Urinary NAA and MRS showing NAA peak are useful in diagnosis of CD. Macrocephaly is not a necessary finding to diagnose CD. Early diagnosis helps in genetic counseling and prevention of subsequent conceptions.

Biotinidase deficiency is a rare autosomal recessive neurometabolic disorder resulting in biotin deficiency. Our patient presented with seizures and developmental delay since infancy and was started on megavitamin supplements. At 14 years, she presented with motor regression with encephalopathy after discontinuation of vitamins. There were no skin and hair changes. Magnetic resonance imaging (MRI) of the brain showed bilateral symmetrical posterior putamen signal changes. Tandem mass spectroscopy showed increased methyl malonyl carnitine and 3-OH isovaleryl carnitine. There was a low biotinidase level, and a pathogenic variant in the BTD gene in the next-generation sequencing was identified. Special importance is placed on the unusual symmetric posterior putamen involvement seen in MRI of the brain.

Subcutaneous granuloma annulare is an uncommon, benign self-limiting cutaneous disease, almost exclusively seen in young children. We report a case of 31-year-old male patient, presented with asymptomatic firm plaques over the left lateral malleoli and dorsum of the feet. Histopathological examination was done to confirm the diagnosis and the lesions responded well to monthly doses of the combination of rifampicin, ofloxacin, minocycline (ROM) therapy and intralesional steroid therapy. This case is reported for its unusual presentation of very large plaque in an adult male and its resolution after combined ROM and intralesional steroid therapy.

Frequency evaluation in rotary engine blade design is an important research area because of its critical applications in aircraft engines and land-based gas engines. A compressor blade plays an important role in increasing pressure and velocity of the fluid, which influences the efficiency of gas turbines. Due to peak centrifugal stresses, gas bending loads and vibratory stresses, flow-induced blade vibrations occur leading to blade catastrophe. The airfoil is expected to prove not only the mechanical efficiency but also mechanical integrity for a desired life. The present research focuses on the study of the vibrational behaviour of an Axial HP Shrouded Compressor blade for in-service conditions. A Computational Fluid Dynamics based model is generated with reference to NACA 65-series, to analyse the flow behaviour through a linear cascade of axial compressor blades, followed by mechanical integrity stress checks to take it further with root attachment design. The present work demonstrates the need for shrouds in compressor rotor blades for stiffening the blade to avoid resonance. The positioning of the shroud is a challenge across the blade height by achieving Frequency Separation Margins using Campbell Diagram, an industry best practice.

BACKGROUND:Government of India is committed to eliminate measles and control rubella/congenital rubella syndrome (CRS) by 2020. In 2016, CRS surveillance was established in five sentinel sites. We analyzed surveillance data to describe the epidemiology of CRS in India. METHODOLOGY/PRINCIPAL FINDINGS:We used case definitions adapted from the WHO-recommended standards for CRS surveillance. Suspected patients underwent complete clinical examination including cardiovascular system, ophthalmic examination and assessment for hearing impairment. Sera were tested for presence of IgM and IgG antibodies against rubella. Of the 645 suspected CRS patients enrolled during two years, 137 (21.2%) were classified as laboratory confirmed CRS and 8 (1.2%) as congenital rubella infection. The median age of laboratory confirmed CRS infants was 3 months. Common clinical features among laboratory confirmed CRS patients included structural heart defects in 108 (78.8%), one or more eye signs (cataract, glaucoma, pigmentary retinopathy) in 82 (59.9%) and hearing impairment in 51. (38.6%) Thirty-three (24.1%) laboratory confirmed CRS patients died over a period of 2 years. Surveillance met the quality indicators in terms of adequacy of investigation, adequacy of sample collection for serological diagnosis as well as virological confirmation. CONCLUSIONS/SIGNIFICANCE:About one fifth suspected CRS patients were laboratory confirmed, indicating significance of rubella as a persistent public health problem in India. Continued surveillance will generate data to monitor the progress made by the rubella control program in the country.

Chromoblastomycosis is a chronic granulomatous infection of the skin and subcutaneous tissue caused by specific group of dematiaceous fungi. The infection results from traumatic injury and is seen more commonly on feet and lower legs. It is rarely seen in children and metastatic spread to other systems is exceptionally rare. We report a 12-year-old immunocompetent male child diagnosed with chromoblastomycosis on the lower leg, who in a span of few months developed osteomyelitis and left hemiparesis. Fungal culture showed growth of Exophiala spinifera. Child showed good improvement with voriconazole and itraconazole after 1 year of treatment. Skin lesions healed with minimal scarring and his power improved.