From tradition to innovation: conventional and deep learning frameworks in genome annotation.

Following the milestone success of the Human Genome Project, the 'Encyclopedia of DNA Elements (ENCODE)' initiative was launched in 2003 to unearth information about the numerous functional elements within the genome. This endeavor coincided with the emergence of numerous novel technologies, accompanied by the provision of vast amounts of whole-genome sequences, high-throughput data such as ChIP-Seq and RNA-Seq. Extracting biologically meaningful information from this massive dataset has become a critical aspect of many recent studies, particularly in annotating and predicting the functions of unknown genes. The core idea behind genome annotation is to identify genes and various functional elements within the genome sequence and infer their biological functions. Traditional wet-lab experimental methods still rely on extensive efforts for functional verification. However, early bioinformatics algorithms and software primarily employed shallow learning techniques; thus, the ability to characterize data and features learning was limited. With the widespread adoption of RNA-Seq technology, scientists from the biological community began to harness the potential of machine learning and deep learning approaches for gene structure prediction and functional annotation. In this context, we reviewed both conventional methods and contemporary deep learning frameworks, and highlighted novel perspectives on the challenges arising during annotation underscoring the dynamic nature of this evolving scientific landscape.

Assessing the efficacy of celecoxib after tonsillectomy and/or adenoidectomy: A systematic review and meta-analysis of randomised control trials.

OBJECTIVES: Tonsillectomy and adenoidectomy are common surgical procedures that cause persistent pain, bleeding, and functional limitations. We aimed to investigate the efficacy of celecoxib compared with a placebo for managing post-tonsillectomy or adenoidectomy pain and other adverse events. DESIGN: Systematic review and meta-analysis. METHODS: We conducted a systematic literature search in the PubMed, Cochrane, and Google Scholar databases from inception until July 2023. Dichotomous outcomes have been reported as risk ratios (RR) while continuous outcomes were reported using mean differences (MD). A funnel plot was drawn to investigate publication bias. RESULTS: From 1394 records identified, 6 randomised double-blind trials comprising 591 participants undergoing tonsillectomy and/or adenoidectomy were eligible for inclusion. A high dose (400 mg) of celecoxib was effective in decreasing the pain score for 'worst pain' after the procedure (MD: -10.98, [95% CI: -11.53, -10.42], p < .01, I2 = 0%) while a low dose (200 mg) was not significantly effective (p = 0.31). For managing other outcomes such as vomiting (RR: 1.37 [95% CI: 0.69, 2.68], p = 0.37, I2 = 67%), diarrhoea (RR: 1.41, [95% CI: 0.75, 2.64], p = .29, I2 = 42%), dizziness/drowsiness (RR: 0.90, [95% CI: 0.71, 1.15], p = .48, I2 = 0%), functional recovery time (p = .74), and headache (p = .91), there was no significant difference between the group on celecoxib and the placebo group regardless of dosage. Finally, there was no significant difference (RR: 1.02, [95% CI: 0.91, 1.15], p = .69, I2 = 0%) in the effect of the intervention on minimum bleeding, moderate bleeding, and profuse bleeding. CONCLUSION: This meta-analysis provides robust evidence pooled from high-quality trials and raises questions about the efficacy of celecoxib for tonsillectomy and/or adenoidectomy, challenging existing perceptions.

Differences in social support, emotion invalidation, psychological needs, cognitive emotion regulation in maritally adjusted and maladjusted women in Pakistan: A matched pairs design.

The present study aimed to find out differences of social support, perceived emotion invalidation, psychological needs, and use of adaptive and maladaptive cognitive emotion regulation strategies in maritally adjusted and maladjusted after controlling for age, education, employment status, and depressive symptomatology. The cross-sectional study uses a matched pairs design. The sample was divided into two groups; maritally adjusted and maladjusted women (n = 40 pairs) on basis of scores obtained on revised-dyadic adjustment scale. Forty maritally adjusted women were matched with 40 maritally maladjusted women according to age, education, and employment status. Social support questionnaire, perceived invalidation of emotion scale, basic psychological need satisfaction frustration scale, cognitive emotion regulation questionnaire, and center for epidemiologic studies depression scale were administered. One-way ANCOVA revealed that maritally maladjusted women had lower level of social support [mean difference; -5.65(-9.97, -1.33), p < 0.05, partial η2 = 0.08] and more emotional invalidation [mean difference; 15.36(13.08, 17.65), p < 0.001, partial η2 = 0.71] compared to maritally adjusted women after controlling for the effect of depressive symptomatology. Maritally maladjusted women had more need frustration [mean difference; 10.75(7.59, 13.92), p < 0.001, partial η2 = 0.38] compared to maritally adjusted women. However, maritally adjusted women had more need satisfaction [mean difference; 13.36(9.67, 17.05), p < 0.001, partial η2 = 0.41] compared to maritally maladjusted women. Maritally adjusted women used more adaptive CER strategies (acceptance, refocus on planning and putting into perspective) [mean difference; 4.66(2.36, 6.95), p < 0.001, partial η2 = 0.18] compared to maritally maladjusted women whereas, maritally maladjusted women used more maladaptive strategies (self-blame, catastrophizing and blaming others) [mean difference; 4.66(2.77, 6.54), p < 0.001, partial η2 = 0.25] compared to maritally adjusted women. Maladjusted women had less social support and more emotional invalidation of emotions and psychological needs frustration. They used more maladaptive strategies to manage their negative emotions in comparison to maritally adjusted women. Identification of these cognitive emotion regulation strategies will help clinicians and counselors to devise psychological intervention targeting the use of adaptive strategies to minimize the negative mental health consequences.

Iron-doped biochar, an agricultural and environmentally beneficial fertilizer.

The utilization of agricultural waste to create value-added goods has benefited waste management while resolving cost-effectiveness and food shortage problems. Returning biochar produced from agricultural waste to the agricultural field is a sustainable method of enhancing crop production while lowering the environmental effect of typical fertilizers. It also enhances soil condition by modulating pH, soil organic carbon, water retention capacity, and soil ion exchange potential. The current work concentrated on the production of iron oxide-loaded biochar from banana peels. Pyrolysis was carried out at temperatures ranging from 400 to 500 °C. The co-precipitation technique was utilized to impregnate Fe3O4 nanoparticles on biochar, and it showed to be an effective and trustworthy method. Loading was done in situ. Characterization techniques such as XRD, FTIR, CHNS, and TGA were employed to characterize synthesized materials. Swelling ratio, water retention, absorbance, and equilibrium water content percentage were used to study the adsorption capabilities of Fe3O4-loaded biochar, soil, and raw biochar. As a consequence, Fe3O4-enriched biochar was shown to have better adsorption capability than raw biochar, which in turn showed better adsorption properties than soil. Iron-loaded biochar was employed as a fertilizer in Abelmoschus esculentus (Okra), and the results showed that it is a cost-effective, environmentally friendly fertilizer.

Variants in FREM1 and trisomy 18 identified in a neonatal progeria patient.

BACKGROUND: Neonatal progeroid disorders are rare disorders with clinical features including low body mass index, proptosis, aged and dysmorphic facial features at the time of birth, prominent veins, sparse scalp hairs, and severe growth retardation. Very few cases have been identified with an unknown genetic cause. Here, we report clinical and genetic findings of a proband with hallmark features of neonatal progeria. METHODS: Microarray comparative genomic hybridization, whole exome sequencing (WES) and Sanger sequencing were performed using standard methods. RESULTS: Array combined genome hybridization data revealed trisomy 18 in the proband (II-1), and WES data identified novel compound heterozygous variants (c.247 C > T; p.H83Y and c.14769868InsA) in the FREM1 gene. CONCLUSION: We report a novel complex case of neonatal progeria with atrial septal defects, trisomy 18 without typical features of Edward syndrome. The phenotype of the patient was more consistent with neonatal progeria, thus we speculate it to be caused by the FREM1 variants.

Comparison of effects of manual physical therapy and exercise therapy for patients with Temporomandibular disorders.

The term temporomandibular disorder is used for pain and dysfunction at the temporomandibular joint. Manual therapy or exercise therapy has proven to be an effective measure for pain relief. The purpose of this study was to compare the effectiveness of manual therapy and exercise therapy in temporomandibular disorders. A quasi-experimental study was conducted from June 30, 2020 to December 30, 2020 in Al-Sheikh teaching hospital, Sialkot, Pakistan. A convenient sample of 24 patients was involved in the study. Lottery method was used to randomise the patients in either the Manual Therapy Group or Exercise Therapy Group. The participants were assessed before and after the intervention through Numeric Pain Rating Scale (NPRS) for pain, Patient-Specific Functional Scale (PSFS) for function, Fonesca Amnestic Index (FAI) for the severity of condition, and Millimetre Mouth Opening (MMO) for ranges. The manual therapy group showed a statistically significant difference in pre- and post-treatment NPRS, PSFS, FAI and MMO (p< 0.0001). Manual physical therapy is more effective to improve pain, ROM, function, and severity in temporomandibular disorders.

Screen Time And Its Relationship With Attention Deficit Hyperactivity Disorder Among Children Attending A Tertiary Care Hospital.

Objective: To estimate the frequency of attention deficit hyperactivity disorder and its relationship with screen time and sociodemographic characteristics among children. METHODS: The cross-sectionalstudy was conducted at the National Institute of Child Health, Karachi, in June-July 2022, and comprised children of either gender aged 5-10 years visiting the paediatric outpatient department. Screen time was measured using a pretested questionnaire, while attention deficit hyperactivity disorder was measured using ADHD rating scale IV. The relationship of sociodemographic characteristics and screen time with the disorder was explored through multiple linear regression analysis. Data was analysed using SPSS 20. RESULTS: Of the 247 participants, 126(51%) were boys and 121(49%) were girls. The overall mean age was 7.84±1.87 years. There were 149(60.3%) children at the primary level of education, while 76(30.8%) had no formal education. There were 139(56.3%) children having screen time >2 hours/day with a mean of 3.36±3.14 hours. There were 15(6.1%) children with attention deficit hyperactivity disorderscore >26 with a mean of 11.58±9.27. Boys were more frequently affected by attention deficit hyperactivity disorder compared to girls (p=0.026), and there was a significant positive correlation between screen time and attention deficit hyperactivity disorder (p<0.001). Conclusion: The majority of children were found to be spending more than the recommended time on screen. Male gender and screen time were associated with attention deficit hyperactivity disorder.

Effect Of Age, Gender And Type Of Varicosity On The Post-Operative Pain Score After Seven-Day Compression Dressing After Varicose Vein Surgery.

Great saphenous vein insufficiency is linked to 80% of all remarkable lower limb varicosities. A total of 30 patients were enrolled from OPD fulfilling the inclusion criteria after the approval of the hospital's ethical committee. Patients had compression dressing for seven days after surgery. The patients were divided into two groups-Group-A (Compression dressing for two days) and Group-B (Compression dressing for seven days). Stratification of pain score was done against age, gender, and grades of varicose veins, and after dividing into groups t- test was put into use. A p 20 value ≤0.05 was contemplated to be remarkable. Thirty patients with primary varicose vein were enrolled in this study. The mean age of patients was 35.4±9.9 years. Mean pain score in these patients was 2.9±0.8 years. Pain score after seven days of compression dressing after the surgery for varicose veins depend upon the gender, age, and grades of the varicosity of the veins. It is lesser in the females, younger age groups, and in those who had initially lesser severity of the varicose veins.

Novel form of rhizomelic skeletal dysplasia associated with a homozygous variant in GNPNAT1.

BACKGROUND: Studies exploring molecular mechanisms underlying congenital skeletal disorders have revealed novel regulators of skeletal homeostasis and shown protein glycosylation to play an important role. OBJECTIVE: To identify the genetic cause of rhizomelic skeletal dysplasia in a consanguineous Pakistani family. METHODS: Clinical investigations were carried out for four affected individuals in the recruited family. Whole genome sequencing (WGS) was completed using DNA from two affected and two unaffected individuals from the family. Sequencing data were processed, filtered and analysed. In silico analyses were performed to predict the effects of the candidate variant on the protein structure and function. Small interfering RNAs (siRNAs) were used to study the effect of Gnpnat1 gene knockdown in primary rat chondrocytes. RESULTS: The patients presented with short stature due to extreme shortening of the proximal segments of the limbs. Radiographs of one individual showed hip dysplasia and severe platyspondyly. WGS data analyses identified a homozygous missense variant c.226G>A; p.(Glu76Lys) in GNPNAT1, segregating with the disease. Glucosamine 6-phosphate N-acetyltransferase, encoded by the highly conserved gene GNPNAT1, is one of the enzymes required for synthesis of uridine diphosphate N-acetylglucosamine, which participates in protein glycosylation. Knockdown of Gnpnat1 by siRNAs decreased cellular proliferation and expression of chondrocyte differentiation markers collagen type 2 and alkaline phosphatase, indicating that Gnpnat1 is important for growth plate chondrocyte proliferation and differentiation. CONCLUSIONS: This study describes a novel severe skeletal dysplasia associated with a biallelic, variant in GNPNAT1. Our data suggest that GNPNAT1 is important for growth plate chondrogenesis.

Biallelic variants in CHST3 cause Spondyloepiphyseal dysplasia with joint dislocations in three Pakistani kindreds.

BACKGROUND: Skeletal dysplasia is a heterogeneous group of disorders. Spondyloepiphyseal dysplasias comprise one subgroup. Deficiency of carbohydrate sulfotransferase 3 has been reported in a small number of patients with recessively inherited spondyloepiphyseal dysplasia with joint dislocation, short stature and scoliosis. We report here molecular and clinical findings of affected individuals in three consanguineous Pakistani families. Affected individuals in all three families had a uniform phenotype including severe short stature, multiple dislocated joints, progressive scoliosis and facial dysmorphism. METHODS: Clinical evaluation was done for three unrelated families. Radiological survey of bones was completed for patients from two of the families. Whole exome sequencing index patients from each family was performed followed by Sanger sequencing for validation of segregation of identified variants in respective families. In-silico analysis for determining pathogenicity of identified variants and conservation was done. RESULTS: Whole-exome sequencing revealed biallelic variants c.590 T > C;p.(Leu197Pro), c.603C > A;p.(Tyr201Ter) and c.661C > T;p.(Arg221Cys) in CHST3 (NM_004273.5) in the three families with eight, five and two affected individuals, respectively. Contrary to previous reports, affected individuals in none of the families exhibited a hearing loss. CONCLUSION: We describe genotypic and phenotypic findings of three unrelated families with spondyloepiphyseal dysplasia. Our study confirms phenotypic variability and adds to the genotypic spectrum of spondyloepiphyseal dysplasia.

Biochar application for the remediation of trace metals in contaminated soils: Implications for stress tolerance and crop production.

In modern agriculture and globalization, the release of trace metals from manufacturing effluents hinders crop productivity by polluting the atmosphere and degrading food quality. Sustaining food safety in polluted soils is critical to ensure global food demands. This review describes the negative effects of trace metals stress on plant growth, physiology, and yield. Furthermore, also explains the potential of biochar in the remediation of trace metal's contaminations in plants by adoption of various mechanisms such as reduction, ion exchange, electrostatic forces of attraction, precipitation, and complexation. Biochar application enhances the overall productivity, accumulation of biomass, and photosynthetic activity of plants through the regulation of various biochemical and physiological mechanisms of plants cultivated under trace metals contaminated soil. Moreover, biochar scavenges the formation of reactive oxygen species, by activating antioxidant enzyme production i.e., ascorbate peroxidase, catalase, superoxide dismutase, peroxidase, etc. The application of biochar also improves the synthesis of stressed proteins and proline contents in plants thus maintaining the osmoprotectant and osmotic potential of the plant under contaminates stress. Integrated application of biochar with other amendments i.e., microorganisms and plant nutrients to improve trace metal remediation potential of biochar and improving crop production was also highlighted in this review. Moreover, future research needs regarding the application of biochar have also been addressed.

Assessment of Binary Agarose-Carbopol Buccal Gels for Mucoadhesive Drug Delivery: Ex Vivo and In Vivo Characterization.

Agarose (AG) is a naturally occurring biocompatible marine seaweed extract that is converted to hydrocolloid gel in hot water with notable gel strength. Currently, its mucoadhesion properties have not been fully explored. Therefore, the main aim of this study was to evaluate the mucoadhesive potential of AG binary dispersions in combination with Carbopol 934P (CP) as mucoadhesive gel preparations. The gels fabricated via homogenization were evaluated for ex vivo mucoadhesion, swelling index (SI), dissolution and stability studies. The mucoadhesive properties of AG were concentration dependent and it was improved by the addition of CP. Maximum mucoadhesive strength (MS) (27.03 g), mucoadhesive flow time (FT) (192.2 min), mucoadhesive time in volunteers (MT) (203.2 min) and SI (23.6% at 4 h) were observed with formulation F9. The mucoadhesive time investigated in volunteers (MT) was influenced by AG concentration and was greater than corresponding FT values. Formulations containing 0.3%, w/v AG (F3 and F9) were able to sustain the release (~99%) for both drugs till 3 h. The optimized formulation (F9) did not evoke any inflammation, irritation or pain in the buccal cavity of healthy volunteers and was also stable up to 6 months. Therefore, AG could be considered a natural and potential polymer with profound mucoadhesive properties to deliver drugs through the mucosal route.

Comparison of outcome of compression dressing for two days Vs seven days after varicose surgery.

Incompetence of the great saphenous vein (GSV) is a global issue and the most prevalent cause of chronic venous disease of the leg. Clinical manifestations range from moderate to severe, including tiredness, heaviness, and irritation, as well as hyperpigmentation and leg ulcers. A study was conducted to address this controversy,1 i.e. to determine the outcome of compression dressing after varicose vein surgery in terms of postoperative pain, on the Surgical floor, of Mayo Hospital, Lahore, from October 1, 2020, to April 1, 2021. A total of 60 patients with Primary varicose veins were enrolled in this study, fulfilling the inclusion criteria after obtaining approval from the ethical committee of the hospital. The patients were divided in two groups. Group A wore compression dressing for two days after surgery and Group B wore compression dressing for seven days after surgery. All the patients received 1gm Paracetamol I/V eight hourly followed by tablet Paracetamol 500mg P/O eight hourly. Then the outcome of compression dressing was analysed in the form of mean postoperative pain. The mean pain score was assessed on one week. Data were entered in SSPS v23.0. Stratification of pain score was done against age, gender, and grades of varicose veins. A comparison of the two groups was done by applying a t-test. A p-value of ≤ 0.05 was considered significant. Prescribing compression stockings for longer than two days after Trendelenburg's procedure leads to reduced pain and improved physical function during the first week after treatment.

RAB33B and PCNT variants in two Pakistani families with skeletal dysplasia and short stature.

BACKGROUND: Skeletal dysplasia is a heterogeneous group of disorders resulting from different genetic variants in humans. The current study was designed to identify the genetic causes of skeletal dysplasia and short stature in two consanguineous families from Pakistan, both comprised of multiple affected individuals. Patients in one family had proportionate short stature with reduced head circumference while affected individuals in the other family had disproportionate short stature. METHODS: Clinical data were obtained and radiological examinations of the index patients were completed. Whole genome sequencing for probands from both families were performed followed by Sanger sequencing to confirm segregation of identified variants in the respective families. In-silico pathogenicity score prediction for identified variant and amino acid conservation analysis was completed. RESULTS: Whole Genome Sequencing identified a known biallelic variant c.6176_6189delGTCAGCTGCCGAAG; p.(Gln2060ArgfsTer48) in PCNT gene and a novel biallelic variant c.174delC; p.(Asp60ThrfsTer7) in RAB33B gene respectively in affected members of the two families. Clinical imaging revealed platyspondyly and varus deformity in the legs of the affected members in the first family. Radiographs indicated severe platyspondyly, genu valgus deformity of legs and pectus carinatum for the patients in the second family. CONCLUSION: In this study we report the phenotypes and genetic variants in two unrelated families with two distinct forms of skeletal dysplasia. This study strengthens the previous findings that patients harboring PCNT variants are phenotypically homogeneous and also extends the genotypic spectrum of RAB33B variants.

Genome-wide identification of ABA receptor PYL/RCAR gene family and their response to cold stress in Medicago sativa L.

Abscisic acid (ABA) is an important phytohormone involved in plant growth, plant development, and the protection of plants against abiotic stresses. PYL/RCAR (pyrabactin resistance/pyr1-like/regulatory components of ABA receptor) is the receptor protein of ABA and the core component of the ABA signal transduction network. The PYL gene family has been identified and analyzed in many species, however, there is no report about the research on the whole genome-wide identification of the alfalfa (Medicago sativa L.) PYL gene family. Therefore, to explore the function of alfalfa PYL genes, 39 MsPYL genes were identified by analyzing the recently published genome of alfalfa. Using bioinformatics methods, we systematically analyzed the chromosome location, protein physicochemical properties, evolutionary relationship, conserved motifs, and response to low-temperature stress of the MsPYL family of alfalfa. The results showed that 39 alfalfa MsPYL genes were distributed on 24 chromosomes, and the analysis of gene duplication events showed that fragment duplication was predominant duplication in alfalfa MsPYL family gene expansion. The phylogenetic tree of MsPYL protein of alfalfa and the phylogenetic tree of PYL genes of 3 species show that the MsPYL gene family can be divided into 3 subfamilies, and the structures of the same subfamilies are relatively similar. The 39 MsPYL gene family members of alfalfa contain 10 Motifs. Motif1, Motif2, Motif3, and Motif5 are the conserved motifs shared by these genes; cis-regulatory elements in promoter regions indicate that regulatory elements related to transcription, cell cycle, development, hormone, and stress response are abundantly present in the MsPYL promoter sequences; Real-time fluorescence quantitative PCR analysis showed that the expression of MsPYL genes can be induced by low-temperature treatment. This study provides a reference for further exploring the structural and functional characterization of the alfalfa PYL gene family. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01066-3.

Role of capping agents in the application of nanoparticles in biomedicine and environmental remediation: recent trends and future prospects.

Capping agents are of utmost importance as stabilizers that inhibit the over-growth of nanoparticles and prevent their aggregation/coagulation in colloidal synthesis. The capping ligands stabilize the interface where nanoparticles interact with their medium of preparation. Specific structural features of nanoparticles are attributed to capping on their surface. These stabilizing agents play a key role in altering the biological activities and environmental perspective. Stearic effects of capping agents adsorbed on the surface of nanoparticles are responsible for such changing physico-chemical and biological characteristics. Firstly, this novel review article introduces few frequently used capping agents in the fabrication of nanoparticles. Next, recent advancements in biomedicine and environmental remediation approaches of capped nanoparticles have been elaborated. Lastly, future directions of the huge impact of capping agents on the biological environment have been summarized.

Management of appendicitis during COVID-19 pandemic; short-term outcomes.

BACKGROUND AND AIM: COVID-19 pandemic has predisposed patients undergoing surgery to post-operative infection and resultant complications. Appendicitis is frequently managed by appendicectomy. After the onset of the pandemic, selected cases of appendicitis were managed with antibiotics which is a recognised treatment option. Our objective was to compare the management of appendicitis and post-operative outcomes between pre- and post-COVID-19. METHODS: Ninety-six patients were identified from before the onset of the pandemic (November 2019) to after the onset of the pandemic (May 2020). Data were collected retrospectively from electronic records including demographics, investigations, treatment, duration of inpatient stay, complications, readmissions and compared between pre- and post-COVID-19 groups. RESULTS: One hundred percent underwent surgical treatment before the onset of pandemic, compared with 56.3% from the onset of the pandemic. A greater percentage of patients were investigated with imaging post-COVID-19 (100% versus 60.9%; p < 0.00001). There was no significant difference in the outcomes between the two groups. CONCLUSION: CT/MRI scan was preferred to laparoscopy in diagnosing appendicitis and conservative management of uncomplicated appendicitis was common practice after the onset of pandemic. Health boards can adapt their management of surgical conditions during pandemics without adverse short-term consequences. Long term follow-up of this cohort will identify patients suitable for conservative management.

Autosomal recessive chondrodysplasia with severe short stature caused by a biallelic COL10A1 variant.

BACKGROUND: Heterozygous mutations in COL10A1 underlie metaphyseal chondrodysplasia, Schmid type (MCDS), an autosomal dominant skeletal dysplasia. OBJECTIVE: To identify the causative variant in a large consanguineous Pakistani family with severe skeletal dysplasia and marked lower limb deformity. METHODS: Whole exome sequencing was completed followed by Sanger sequencing to verify segregation of the identified variants. In silico variant pathogenicity predictions and amino acid conservation analyses were performed. RESULTS: A homozygous c.133 C>T (p.Pro45Ser) variant was identified in COL10A1 in all six severely affected individuals (adult heights 119-130 cm, mean ~-6.33 SD). The individuals heterozygous for the variant had mild phenotype of short stature (adult heights 140-162 cm, mean ~-2.15 SD) but no apparent skeletal deformities. The variant was predicted to be pathogenic by in silico prediction tools and was absent from public databases and hundred control chromosomes. Pro45 is conserved in orthologues and is located in the non-collagenous 2 domain of COL10A1, variants of which have never been associated with skeletal dysplasia. CONCLUSIONS: This first report of individuals with a homozygous variant in COL10A1 defines a new type of autosomal recessive skeletal dysplasia. The observations in COL10A1 variant carriers suggest a phenotypic overlap between the mildest forms of MCDS and idiopathic short stature.

Hepatoprotective effects of ethanolic extract of Boerhaavia diffusa against oxaliplatin induced hepatotoxicity in albino rats.

The hepatoprotective effects of Boerhaavia diffusa was studied against the hepatotoxicity induced by oxaliplatin. Male Wistar rats were divided in three groups.Group N* control group (0.9% normal saline), Group NP0 oxaliplatin treated group and Group NP2 were prophylactically treated with Boerhaavia diffusa and then with oxaliplatin in order to assess the protective effects of Boerhaavia diffusa against the toxicity of oxaliplatin. The levels of liver enzymes ALT, AST and γ-GT were significantly reduced in the group prophylactically treated with Boerhaavia diffusa (NP2) compared with the group treated with oxaliplatin (NP0). Boerhaavia diffusa was effective in reducing risk of hypercholestremia associated with oxaliplatin. Histopathological examination of rat liver revealed that prophylactically treated group with Boerhaavia diffusa was effective in reducing oxidative stress induced steatohepatitis by oxaliplatin.