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Mucolipidosis (ML) (OMIM 607840 & 607838) is a rare autosomal recessive inherited disorder that occurs due to the deficiency of golgi enzyme uridine diphosphate (UDP)– N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) responsible for tagging mannose-6-phosphate for proper trafficking of lysosomal enzymes to lysosomes. Variants in GlcNAc-phosphotransferase (GNPTAB (α, β subunits) and GNPTG (γ subunits) are known to result in impaired targeting of lysosomal enzymes leading to Mucolipidosis (ML) Type II or Type III. We analyzed 69 Indian families of MLII/III for clinical features and molecular spectrum and performed in silico analysis for novel variants. We identified 38 pathogenic variants in GNPTAB and 5 pathogenic variants in GNPTG genes including missense, frame shift, deletion, duplication and splice site variations. A total of 26 novel variants were identified in GNPTAB and 4 in GNPTG gene. In silico studies using mutation prediction software like SIFT, Polyphen2 and protein structure analysis further confirmed the pathogenic nature of the novel sequence variants detected in our study. Except for a common variant c.3503_3504delTC in early onset MLII, we could not establish any other significant genotype and phenotype correlation. This is one of the largest studies reported till date on Mucolipidosis II/III in order to identify mutation spectrum and any recurrent mutations specific to the Indian ethnic population. The mutational spectrum information in Indian patients will be useful in better genetic counselling, carrier detection and prenatal diagnosis for patients with ML II/III.

Although brain injury after neonatal encephalopathy has been characterised well in high-income countries, little is known about such injury in low- and middle-income countries. Such injury accounts for an estimated 1 million neonatal deaths per year. We used magnetic resonance (MR) biomarkers to characterise perinatal brain injury, and examined early childhood outcomes in South India. We recruited consecutive term or near term infants with evidence of perinatal asphyxia and a Thompson encephalopathy score ≥6 within 6 h of birth, over 6 months. We performed conventional MR imaging, diffusion tensor MR imaging and thalamic proton MR spectroscopy within 3 weeks of birth. We computed group-wise differences in white matter fractional anisotropy (FA) using tract based spatial statistics. We allocated Sarnat encephalopathy stage aged 3 days, and evaluated neurodevelopmental outcomes aged 3½ years using Bayley III. Of the 54 neonates recruited, Sarnat staging was mild in 30 (56%); moderate in 15 (28%) and severe in 6 (11%), with no encephalopathy in 3 (6%). Six infants died. Of the 48 survivors, 44 had images available for analysis. In these infants, imaging indicated perinatal rather than established antenatal origins to injury. Abnormalities were frequently observed in white matter (n = 40, 91%) and cortex (n = 31, 70%) while only 12 (27%) had abnormal basal ganglia/thalami. Reduced white matter FA was associated with Sarnat stage, deep grey nuclear injury, and MR spectroscopy N-acetylaspartate/choline, but not early Thompson scores. Outcome data were obtained in 44 infants (81%) with 38 (79%) survivors examined aged 3½ years; of these, 16 (42%) had adverse neurodevelopmental outcomes. No infants had evidence for established brain lesions, suggesting potentially treatable perinatal origins. White matter injury was more common than deep brain nuclei injury. Our results support the need for rigorous evaluation of the efficacy of rescue hypothermic neuroprotection in low- and middle-income countries.

Finger millet production in India has decreased in recent decades, primarily due to challenges such as drought, inadequate market support, and cultural barriers. Against this backdrop, the present study examines the economic viability of finger millet cultivation in Karnataka, the state with the largest share of finger millet production. Specifically, it examines (i) the cost of cultivation, returns, and profitability; (ii) the relationship between inputs and output through the application of the Cobb-Douglas production function and decomposition analysis, The study is based on the cost of cultivation survey data published by the Commission of Agricultural Costs and Prices (CACP) and the Indian Institute of Millet Research (IIMR) for 2001–2020. Results revealed that the total cost of cultivation increased sharply from ₹13,125.17/ha in 2001 to ₹79,025/ha in 2020, primarily driven by escalating labour and input expenses. Although gross income rose substantially during the same period, profitability under comprehensive cost (C2) remained negative, reflecting persistent cost pressures. Break-even analysis indicated that actual yield remained below the threshold level in most years. The highest negative deviation was observed in 2011, with the actual yield (20.15 q/ha) falling 15.05 q/ha (-42.75 percent) short of the break-even yield (35.20 q/ha), underscoring the vulnerability of rainfed systems to climatic shocks and drought conditions. The total cost of cultivation increased sixfold from ₹13,125/ha in 2001 to ₹79,025/ha in 2020, mainly driven by sharp rises in human labour (785%), seed (599%), and rental values (706%). Although gross income rose to ₹73,014/ha by 2020, profitability remained negative under comprehensive cost (C2), with losses reaching –₹6,011/ha. The Cobb–Douglas production function explained 61 percent of the output variation, identifying seed, fertilizer, human labour, and animal labour as significant contributors to yield, with fertiliser having the highest positive effect of 0.35. The sum of input elasticities (1.06) indicated increasing returns to scale, suggesting potential efficiency gains through integrated input use. Decomposition analysis revealed that total factor productivity (TFP) contributed 46.73 percent to output growth, underscoring the significant role of technological advancements and improved management practices. The study concludes that profitability cannot be sustained without reducing labour costs, strengthening value chain incentives, and promoting climate-resilient and mechanised cultivation practices. Policies supporting processing, MSP revision, and input-efficient technologies are essential to revive finger millet production under rainfed conditions.

Purpose Genitopatellar syndrome and Say–Barber–Biesecker–Young–Simpson syndrome are caused by variants in the KAT6B gene and are part of a broad clinical spectrum called KAT6B disorders, whose variable expressivity is increasingly being recognized. Methods We herein present the phenotypes of 32 previously unreported individuals with a molecularly confirmed diagnosis of a KAT6B disorder, report 24 new pathogenic KAT6B variants, and review phenotypic information available on all published individuals with this condition. We also suggest a classification of clinical subtypes within the KAT6B disorder spectrum. Results We demonstrate that cerebral anomalies, optic nerve hypoplasia, neurobehavioral difficulties, and distal limb anomalies other than long thumbs and great toes, such as polydactyly, are more frequently observed than initially reported. Intestinal malrotation and its serious consequences can be present in affected individuals. Additionally, we identified four children with Pierre Robin sequence, four individuals who had increased nuchal translucency/cystic hygroma prenatally, and two fetuses with severe renal anomalies leading to renal failure. We also report an individual in which a pathogenic variant was inherited from a mildly affected parent. Conclusion Our work provides a comprehensive review and expansion of the genotypic and phenotypic spectrum of KAT6B disorders that will assist clinicians in the assessment, counseling, and management of affected individuals.

BackgroundDyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC types 1 and 2) are rare spondyloepimetaphyseal dysplasias with identical radiological findings. The presence of intellectual disability in DMC and normal intellect in SMC differentiates the two. DMC and SMC1 are allelic and caused by homozygous or compound heterozygous variants in DYM. SMC2 is caused by variations in RAB33B. Both DYM and RAB33B are important in intravesicular transport and function in the Golgi apparatus.MethodsDetailed clinical phenotyping and skeletal radiography followed by molecular testing were performed in all affected individuals. Next-generation sequencing and Sanger sequencing were used to confirm DYM and RAB33B variants. Sanger sequencing of familial variants was done in all parents.Results24 affected individuals from seven centres are described. 18 had DMC and 6 had SMC2. Parental consanguinity was present in 15 of 19 (79%). Height <3 SD and gait abnormalities were seen in 20 and 14 individuals, respectively. The characteristic radiological findings of lacy iliac crests and double-humped vertebral bodies were seen in 96% and 88% of the affected. Radiological findings became attenuated with age. 23 individuals harboured biallelic variants in either DYM or RAB33B. Fourteen different variants were identified, out of which 10 were novel. The most frequently occurring variants in this group were c.719 C>A (3), c.1488_1489del (2), c.1484dup (2) and c.1563+2T>C (2) in DYM and c.400C>T (2) and c.186del (2) in RAB33B. The majority of these have not been reported previously.ConclusionThis large cohort from India contributes to the increasing knowledge of clinical and molecular findings in these rare ‘Golgipathies’.

Justification The diagnosis of Down syndrome (DS) is easily made clinically but the management is multi-disciplinary and life-long. There is no standard protocol available for its management in India. Process A committee was formed under the Indian Academy of Pediatrics (IAP) chapter of Neuro developmental pediatrics consisting of 20 experts working in the related field. The various aspects of the condition were discussed and allotted to the concerned experts related for preparing the guidelines. The material received was collated to form a set of guidelines, which were reviewed by the committee, and a consensus statement made. The guidelines were then approved by the chapter, and by the IAP. Objectives To define the condition and to look into the various aspects of antenatal and postnatal diagnosis. To explain briefly about the involvement of the various systems that are involved and formulate recommendations for management. To recommend early and sustained interventional therapies to enable children with DS lead an independent life. Recommendations The stress on bio-psycho-social strategy for the management of children with DS is reiterated, and the need for a medical, social and rights model is recommended after each section. The age-wise recommendations are also highlighted in addition to the recommendations under each system.

Background Therapeutic hypothermia reduces death and disability after moderate or severe neonatal encephalopathy in high-income countries and is used as standard therapy in these settings. However, the safety and efficacy of cooling therapy in low- and middle-income countries (LMICs), where 99% of the disease burden occurs, remains unclear. We will examine whether whole body cooling reduces death or neurodisability at 18–22 months after neonatal encephalopathy, in LMICs. Methods We will randomly allocate 408 term or near-term babies (aged ≤ 6 h) with moderate or severe neonatal encephalopathy admitted to public sector neonatal units in LMIC countries (India, Bangladesh or Sri Lanka), to either usual care alone or whole-body cooling with usual care. Babies allocated to the cooling arm will have core body temperature maintained at 33.5 °C using a servo-controlled cooling device for 72 h, followed by re-warming at 0.5 °C per hour. All babies will have detailed infection screening at the time of recruitment and 3 Telsa cerebral magnetic resonance imaging and spectroscopy at 1–2 weeks after birth. Our primary endpoint is death or moderate or severe disability at the age of 18 months. Discussion Upon completion, HELIX will be the largest cooling trial in neonatal encephalopathy and will provide a definitive answer regarding the safety and efficacy of cooling therapy for neonatal encephalopathy in LMICs. The trial will also provide important data about the influence of co-existent perinatal infection on the efficacy of hypothermic neuroprotection. Trial registration ClinicalTrials.gov, NCT02387385 . Registered on 27 February 2015.

If you want to get ahead in your career, it is not enough spending lots of time in your office or place of work. You need to continuously improve yourself. You need to improve on your current skills, learn new skills, learn more in your area of activity and other related areas through education, training and spending useful time in discussion with experts. The biggest obstacle to survival in your career is complacency, or feeling satisfied with what you are doing. The minute you stop growing the world starts passing by and you are soon left behind. Your friends, colleagues and others, who are ambitious, start performing better than you. You lose the ability to perform satisfactorily your current job because the expectations from your superiors have grown. The moment you are reluctant to explore new ideas, new options or new approaches that is the moment you have allowed yourself to become obsolete.

Crigler-Najjar syndrome type 2 is a rare cause for persistent unconjugated hyperbilirubinemia, inherited in an autosomal recessive manner. Even though it is compatible with normal life span, in the absence of prompt suspicion and intensive management it can prove fatal not only in the neonatal period but also during adult life. Here, we describe a case with a novel homozygous UGT1A1 p.Pro176Leu mutation.

Carbon availability is a central determinant of beneficial plant–fungal associations, and sugar transporters are key levers of this exchange. SWEETs (SUGARS WILL EVENTUALLY BE EXPORTED TRANSPORTER) are involved in transporting various kinds of sugars in plants; however, their functional roles in fungal symbiosis are not sufficiently explored. In this study, we investigate the functional relevance of Arabidopsis SWEETs in the interaction with endophytic fungi, Serendipita indica. Transcript profiling of SWEET genes in response to S. indica and its major elicitor, cellotriose, revealed early root-specific induction of SWEET12. Using a SWEET12 loss-of-function mutant, we demonstrate that the absence of SWEET12 disrupts the major outcomes of mutualism including growth promotion, balanced colonization, sugar allocation, and the accumulation of defense phytohormones (JA and SA). Transcriptome profiling further reveals that SWEET12 buffers whole-plant responses by coordinating genes linked to carbohydrate, nitrogen, and lipid metabolism, and by tuning defense signalling and nutrient transporter networks. Our findings indicate that SWEET12 is essential for balancing fungal colonization and host defense, thereby promoting plant growth. SWEET12 does so by acting as sugar valve that meters sugar release to the apoplast, enabling the fungus to access carbon while preserving host sugar homeostasis and immune competence.