The profile of disaster risk of Pakistan and institutional response

Número monográfic

Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins, and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Utilizing exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with YnMyr chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), with ages ranging from 1 to 50 years old, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%), and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%), and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%), and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each), as well as hypertrophy of the clava (24%) were common neuroimaging findings. acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism, and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localisation and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-Myristoylation was similarly affected in acbd6-deficient zebrafish and Xenopus tropicalis models, including Fus, Marcks, and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders

Fungal systematics and evolution : FUSE 6

Fungal Systematics and Evolution (FUSE) is one of the journal series to address the “fusion” between morphological data and molecular phylogenetic data and to describe new fungal taxa and interesting observations. This paper is the 6th contribution in the FUSE series—presenting one new genus, twelve new species, twelve new country records, and three new combinations. The new genus is: Pseudozeugandromyces (Laboulbeniomycetes, Laboulbeniales). The new species are: Albatrellopsis flettioides from Pakistan, Aureoboletus garciae from Mexico, Entomophila canadense from Canada, E. frigidum from Sweden, E. porphyroleucum from Vietnam, Erythrophylloporus flammans from Vietnam, Marasmiellus boreoorientalis from Kamchatka Peninsula in the Russian Far East, Marasmiellus longistipes from Pakistan, Pseudozeugandromyces tachypori on Tachyporus pusillus (Coleoptera, Staphylinidae) from Belgium, Robillarda sohagensis from Egypt, Trechispora hondurensis from Honduras, and Tricholoma kenanii from Turkey. The new records are: Arthrorhynchus eucampsipodae on Eucampsipoda africanum (Diptera, Nycteribiidae) from Rwanda and South Africa, and on Nycteribia vexata (Diptera, Nycteribiidae) from Bulgaria; A. nycteribiae on Eucampsipoda africanum from South Africa, on Penicillidia conspicua (Diptera, Nycteribiidae) from Bulgaria (the first undoubtful country record), and on Penicillidia pachymela from Tanzania; Calvatia lilacina from Pakistan; Entoloma shangdongense from Pakistan; Erysiphe quercicola on Ziziphus jujuba (Rosales, Rhamnaceae) and E. urticae on Urtica dioica (Rosales, Urticaceae) from Pakistan; Fanniomyces ceratophorus on Fannia canicularis (Diptera, Faniidae) from the Netherlands; Marasmiellus biformis and M. subnuda from Pakistan; Morchella anatolica from Turkey; Ophiocordyceps ditmarii on Vespula vulgaris (Hymenoptera, Vespidae) from Austria; and Parvacoccum pini on Pinus cembra (Pinales, Pinaceae) from Austria. The new combinations are: Appendiculina gregaria, A. scaptomyzae, and Marasmiellus rodhallii. Analysis of an LSU dataset of Arthrorhynchus including isolates of A. eucampsipodae from Eucampsipoda africanum and Nycteribia spp. hosts, revealed that this taxon is a complex of multiple species segregated by host genus. Analysis of an SSU–LSU dataset of Laboulbeniomycetes sequences revealed support for the recognition of four monophyletic genera within Stigmatomyces sensu lato: Appendiculina, Fanniomyces, Gloeandromyces, and Stigmatomyces sensu stricto. Finally, phylogenetic analyses of Rhytismataceae based on ITS–LSU ribosomal DNA resulted in a close relationship of Parvacoccum pini with Coccomyces strobi.http://www.sydowia.at/index.htmpm2021Medical Virolog

Uncovering the link between celiac disease and hypopituitarism: a case report and review of literature

Abstract Background Celiac disease, an autoimmune condition triggered by gluten-containing diet, is known to primarily manifest as intestinal symptoms, but can also lead to extraintestinal complications, including endocrine abnormalities and autoimmune disorders. This case report outlines a patient with celiac disease who developed hypopituitarism and explores the possible pathophysiological links between these two conditions. Case presentation We report a case of a 19-year-old female who presented with lethargy, weakness, delayed menarche, and failure to thrive. Subsequent investigations revealed microcytic anemia with decreased serum ferritin and vitamin D levels. Following the identification of abnormal bone age on X-ray, a hormonal profile was requested which revealed panhypopituitarism. After undergoing a diagnostic workup for her gastrointestinal symptoms, she was eventually diagnosed with celiac disease, and her symptoms improved significantly following gluten restriction. Conclusion Panhypopituitarism has a possible association with celiac disease, and this case highlights the importance of close monitoring and appropriate management to prevent long-term health consequences. Additional research is necessary to gain a comprehensive understanding of the link between celiac disease and endocrine disorders

Late Acceptance Hill Climbing Algorithm For Solving Patient Facing Problems In Hospitals

The current study is to evaluate the patient facing problems by applying Late Acceptance Hill Climbing Algorithm (LAHC) in hospital settings. The recent proposed procedure of LAHC is based on metaheuristic algorithm which is linked with one-point clarification method. Patient’s satisfaction regarding the performance of the hospital is a composite mechanism. The optimization procedure is connected with NP-hard problems which is practically related to the problems faced by patients. These problems are concerned with assigning the group of patients visiting the hospital for receiving healthcare services. The common issues faced by patients include communication gap, response time to attend patients, early symptomatic relief, getting proper advice for dosage and usage of medicines, clean hospital environment. Moreover, patient education and guidance before discharge from hospital is also the missing element. The suggested algorithm of LAHC to PFP is developed and it has two phases: the first phase includes providing the initial feasible solution using communication-oriented methodology. The second phase uses three neighborhood framework which are implanted inside the segment of PFP based on LAHC to additionally upgrade the underlying feasible solution of the introductory phase

Effect of Traditional Spices on the Quality and Antioxidant Potential of Paneer Prepared from Buffalo Milk

This study aims to evaluate the effect of different spices (black pepper, cumin, clove, nigella, cardamom, and cinnamon) on the physicochemical characteristics and microbial quality, as well as antioxidant potential, of paneer during storage. Different types of spices were incorporated into the paneer at different levels (0.2 and 0.3%). In addition to paneer, the antioxidant potential of spices was also investigated. The results concerning total plate counts (TPC) or yeast and molds (Y & M) (log10 CFU/g) of all treatments were substantially (p  0.05) increased during storage. Generally, all freshly prepared spicy paneer and control had higher sensory scores for all the sensory characteristics which declined during subsequent storage. All the paneer samples having 0.3% spices showed very slight variations (nonsignificant) in sensory score of all the attributes of their relative samples containing 0.2% spice. The incorporation of spices into the paneer matrix also showed promising results concerning all the above-mentioned attributes revealing antioxidant potential. There was significant (p  0.05) effect of treatments and storage days on antioxidant potential of paneer. The freshly prepared control paneer (P0) showed the lowest total phenol (TP), total flavonoids (TF), 2, 2-diphenyl-1-picrylhydrazyl (DPPH), reducing power (RP), and total antioxidant capacity (TAC) values compared to all the spicy paneer (treatments). The freshly prepared control paneer (P0) showed the lowest antioxidant potential compared to all the spicy paneer (treatments). The maximum antioxidant potential was observed in the paneer having 0.3% clove (P6). All the spicy paneer showed increasing trend of all the attributes, showing antioxidant potential up to 6 days of storage, but afterwards, the activities were slightly decreased. It may be concluded that spicy paneer would be considered as a functional dairy product with enhanced sensory and antioxidant properties, and shelf stability