BACKGROUND: Myogenic Arthrogryposis Multiplex Congenita type 3 (AMC-3), is a rare congenital condition characterized by severe hypotonia, club feet, and multiple joint contractures often affecting both arms and legs which start prior to birth.

CASE PRESENTATION: We report a full-term neonate born to first-degree cousins from fourth-generation consanguineous families, who had with antenatal history of reduced fetal movements. At birth, he was noticed to have bilateral club feet, arthrogryposis, severe hypotonia, and absent deep tendon reflexes. The patient developed difficulty in breathing probably attributed to his generalized severe hypotonia, necessitating mechanical ventilation. His creatinine-phospho-kinase, electromyogram, and brain magnetic resonance imaging were normal. Whole-exome sequencing (WES) was requested for the genetic diagnosis of the case. WES identified a novel homozygous variant c.23415-3799C > G p. in the synaptic nuclear envelope protein1 [SYNE1] gene. Seven out of 20 bioinformatic in silico programs predicted a pathogenic effect for this variant. Segregation analysis of the variant in the parents and siblings revealed that both parents and one sibling were heterozygous for the same mutation which proved the variant significance and its autosomal recessive pattern of inheritance.

CONCLUSIONS: AMC3 should be suspected in patients with decreased fetal movements, severe hypotonia, absent deep tendon reflexes, and arthrogryposis. SYNE1 gene mutations can be the underlying genetic defect and molecular genetic testing can prove the diagnosis.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent, yet largely underappreciated liver condition which is closely associated with obesity and metabolic disease. Despite affecting an estimated 1 in 4 adults globally, NAFLD is largely absent on national and global health agendas.

METHODS: We collected data from 102 countries, accounting for 86% of the world population, on NAFLD policies, guidelines, civil society engagement, clinical management, and epidemiologic data. A preparedness index was developed by coding questions into 6 domains (policies, guidelines, civil awareness, epidemiology and data, NAFLD detection, and NAFLD care management) and categorising the responses as high, medium, and low; a multiple correspondence analysis was then applied.

RESULTS: The highest scoring countries were India (42.7) and the United Kingdom (40.0), with 32 countries (31%) scoring zero out of 100. For 5 of the domains a minority of countries were categorised as high-level while the majority were categorised as low-level. No country had a national or sub-national strategy for NAFLD and <2% of the different strategies for related conditions included any mention of NAFLD. National NAFLD clinical guidelines were present in only 32 countries.

CONCLUSIONS: Although NAFLD is a pressing public health problem, no country was found to be well prepared to address it. There is a pressing need for strategies to address NAFLD at national and global levels.

LAY SUMMARY: Around a third of the countries scored a zero on the NAFLD policy preparedness index, with no country scoring over 50/100. Although NAFLD is a pressing public health problem, a comprehensive public health response is lacking in all 102 countries. Policies and strategies to address NAFLD at the national and global levels are urgently needed.

PURPOSE: The cardio-respiratory function is compromised in children recovering from burns, particularly, those who sustain a burn injury across the chest, which leads to further prejudicial effects on physical and psychosocial health. This study endeavored to explore the efficacy of 12 weeks of graded aerobic exercise (GAEx) on the cardiorespiratory capacity and physical and psychosocial functioning in children with burn sequelae of the chest.

METHODS: Thirty-six burn-injured children aged 10-18 years (%TBSA: 24.2 ± 4.9, and 38.8 ± 12.9 months since injury) were randomly assigned to GAEx group (n = 18; undergone a 12-week intensity- and time-graded aerobic exercise program plus standard rehabilitation) or control group (n = 18; received the standard rehabilitation only). The cardio-respiratory fitness [marked by the peak oxygen uptake (VO), minute ventilation (V), ventilatory equivalent of inhaled oxygen (VEq/VO), oxygen pulse (OP), respiratory exchange ratio (RER), maximum heart rate (HR), and the heart rate recovery at one minute (HRR)] and physical and psychosocial functioning were assessed pre- and post-intervention.

RESULTS: Children in the GAEx group showed significant increases in VO (P = 0.013), V (P = 0.026), OP (P = 0.034), HR (P = 0.035), and HRR (P = 0.04) and declines in VEq/VO (P = 0.009) and RER (P = 0.011) as compared to the control group. Additionally, the GAEx group reported higher physical (P = 0.029) and psychosocial (P = 0.012) functioning.

CONCLUSION: Twelve weeks of GAEx has salutary effects on cardio-respiratory capacity and physical and psychosocial functioning in children with burn sequelae of the chest. These findings suggest that adding GAEx as a complementary therapy to the long-term rehabilitation protocol for this patient population is worthwhile.

n/a

Lung cancer is the second-most deadly malignancy worldwide, of which smoking is considered a major risk factor and causes 75-80% of lung cancer-related deaths. Costunolide (CTD) extracted from plant species exhibits potent anticancer properties, specifically in lung cancer and leukemia. Several nanoemulsions were prepared and optimized using a three-factor Box-Behnken experimental design. The optimized green nanoemulsion (GNE) showed a vesicle size of 199.56 nm. The IC values revealed that A549 cells were significantly more sensitive to the optimized CTD formula than the plain formula and raw CTD. A cell cycle analysis revealed that the optimized CTD formula treatment resulted in significant cell cycle arrest at the S phase. The results also indicated that treatment with the CTD formula significantly increased caspase-3, Bax, Bcl-2, and p53 mRNA expression compared to the plain formula and CTD raw. In terms of the inflammatory markers, the optimized formula significantly reduced the activity of TNF-α and NF-κB in comparison with the plain formula and raw drug only. Overall, the findings from the study proved that a CTD GNE formulation could be a promising therapeutic approach for the treatment of lung cancer.