Rhythmic firing patterns in SCN: The role of circuit interactions

The suprachiasmatic nucleus (SCN) is believed to contain the main generator of circadian rhythmicity in mammals. In order to obtain further functional details of this, electrophysiological extracellular measurements in vitro were made. By means of an interspike interval distribution analysis, it is shown that there is a novel kind of neuronal firing pattern: the harmonic pattern. From these observations, we have developed a theoretical model based on possible filtering processes occurring during synaptic transmission. The model suffices to infer that regular ultradian oscillators could be an emergent property of circuit interactions of cells in the suprachiasmatic nucleus

Pseudohypoparathyroidism type 1A and Albright hereditary osteodystrophy: a comprehensive review of molecular pathogenesis, clinical manifestations, and therapeutic approaches

Pseudohypoparathyroidism type 1A (PHP1A) is a rare genetic disorder characterized by end-organ resistance to parathyroid hormone (PTH) due to heterozygous inactivating mutations in the GNAS gene. Patients frequently exhibit the phenotypic features of Albright hereditary osteodystrophy (AHO), including short stature, brachydactyly, subcutaneous ossifications, and obesity. Despite advances in molecular genetics, the clinical management of PHP1A remains challenging due to its multisystemic involvement. This review aims to elucidate the molecular mechanisms underlying PHP1A, delineate its clinical and biochemical characteristics, and discuss current and emerging therapeutic strategies. A systematic literature review was conducted, analyzing peer-reviewed articles from PubMed, Scopus, and OMIM databases focusing on PHP1A, AHO, and related disorders. PHP1A arises from maternal transmission of GNAS mutations, leading to impaired Gsα protein function and subsequent hormonal resistance. The AHO phenotype is present in most cases, with additional endocrine abnormalities such as hypothyroidism and growth hormone deficiency commonly reported. Early diagnosis is essential to mitigate complications, including severe hypocalcemia and neurocognitive impairments. Treatment involves calcium and vitamin D supplementation, though targeted therapies remain under investigation. PHP1A with AHO represents a complex multisystem disorder necessitating a multidisciplinary approach. Further research into genotype-phenotype correlations and novel therapeutic interventions is warranted to improve patient outcomes

Estimation of water erosion in the Necaxa system, Puebla, Mexico

Objective: To estimate the potential and current water erosion in the Necaxa system and to propose alternatives aimed to reduce the siltation problem in the hydraulic infrastructure.Design/methodology/approach: The Universal Soil Loss Equation (USLE) was applied, using a Geographic Information System to process the map algebra.Results: The current estimated water erosion was 159 t ha1 per year; this factor impacts the loss of farmland and soil nutrients, the accumulation of matter towards urban areas, the siltation of riverbeds and dams, and the loss of the system’s hydraulic works capacity.Study limitations/implications: No data about runoff plots in the field is available; therefore, it is not possible to compare current water erosion values with those obtained by the USLE applied, using the map algebra technique.Findings/conclusions: The reforestation and conservation agriculture proposal would help to reduce erosion to 16 t ha1 per year. However, if control actions are not carried out and the current vegetation cover is not preserved, the problem can increase until it reaches potential erosion values 200 t ha1 per year

Reductions in hypothalamic Gfap expression, glial cells and α-tanycytes in lean and hypermetabolic Gnasxl-deficient mice

BACKGROUND: Neuronal and glial differentiation in the murine hypothalamus is not complete at birth, but continues over the first two weeks postnatally. Nutritional status and Leptin deficiency can influence the maturation of neuronal projections and glial patterns, and hypothalamic gliosis occurs in mouse models of obesity. Gnasxl constitutes an alternative transcript of the genomically imprinted Gnas locus and encodes a variant of the signalling protein Gαs, termed XLαs, which is expressed in defined areas of the hypothalamus. Gnasxl-deficient mice show postnatal growth retardation and undernutrition, while surviving adults remain lean and hypermetabolic with increased sympathetic nervous system (SNS) activity. Effects of this knock-out on the hypothalamic neural network have not yet been investigated. RESULTS: RNAseq analysis for gene expression changes in hypothalami of Gnasxl-deficient mice indicated Glial fibrillary acid protein (Gfap) expression to be significantly down-regulated in adult samples. Histological analysis confirmed a reduction in Gfap-positive glial cell numbers specifically in the hypothalamus. This reduction was observed in adult tissue samples, whereas no difference was found in hypothalami of postnatal stages, indicating an adaptation in adult Gnasxl-deficient mice to their earlier growth phenotype and hypermetabolism. Especially noticeable was a loss of many Gfap-positive α-tanycytes and their processes, which form part of the ependymal layer that lines the medial and dorsal regions of the 3(rd) ventricle, while β-tanycytes along the median eminence (ME) and infundibular recesses appeared unaffected. This was accompanied by local reductions in Vimentin and Nestin expression. Hypothalamic RNA levels of glial solute transporters were unchanged, indicating a potential compensatory up-regulation in the remaining astrocytes and tanycytes. CONCLUSION: Gnasxl deficiency does not directly affect glial development in the hypothalamus, since it is expressed in neurons, and Gfap-positive astrocytes and tanycytes appear normal during early postnatal stages. The loss of Gfap-expressing cells in adult hypothalami appears to be a consequence of the postnatal undernutrition, hypoglycaemia and continued hypermetabolism and leanness of Gnasxl-deficient mice, which contrasts with gliosis observed in obese mouse models. Since α-tanycytes also function as adult neural progenitor cells, these findings might indicate further developmental abnormalities in hypothalamic formations of Gnasxl-deficient mice, potentially including neuronal composition and projections

Estimation of water erosion in the Necaxa system, Puebla, Mexico

Objective: Estimate potential and current water erosion in the Necaxa System and propose alternatives to reduce the problem of siltation of the hydraulic infrastructure Design/methodology/approach: The Universal Soil Loss equation will be applied through algebra of maps processed in a Geographic Information System. Results: It was estimated that the current water erosion in the Necaxa system is 159 tons / ha * year, a factor that affects the loss of land for crops, loss of nutrients in the soil, accumulation of material towards urban areas, silting up of streams, reservoirs and loss of capacity of the hydraulic works of the system. Limitations on study/implications: There is no information on runoff batches in the field that allows the current water erosion values to be compared with those obtained by the EUPS applied by map algebra. Findings/conclusions: By proposing reforestation and carrying out conservation agriculture, it could be reduced to 16 tons / ha * year. However, if control actions are not carried out and the current coverage is not preserved, the problem can increase until reaching potential erosion values higher than 200 ton / ha * year.Objective: To estimate the potential and current water erosion in the Necaxa system and to propose alternatives aimed to reduce the siltation problem in the hydraulic infrastructure.Design/methodology/approach: The Universal Soil Loss Equation (USLE) was applied, using a Geographic Information System to process the map algebra.Results: The current estimated water erosion was 159 t ha-1 per year; this factor impacts the loss of farmland and soil nutrients, the accumulation of matter towards urban areas, the siltation of riverbeds and dams, and the loss of the system’s hydraulic works capacity.Study limitations/implications: No data about runoff plots in the field is available; therefore, it is not possible to compare current water erosion values with those obtained by the USLE applied, using the map algebra technique. Findings/conclusions: The reforestation and conservation agriculture proposal would help to reduce erosion to 16 t ha -1 per year. However, if control actions are not carried out and the current vegetation cover is not preserved, the problem can increase until it reaches potential erosion values >200 t ha -1 per year

Dialysis initiation, modality choice, access, and prescription: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Globally, the number of patients undergoing maintenance dialysis is increasing, yet throughout the world there is significant variability in the practice of initiating dialysis. Factors such as availability of resources, reasons for starting dialysis, timing of dialysis initiation, patient education and preparedness, dialysis modality and access, as well as varied \u201ccountry-specific\u201d factors significantly affect patient experiences and outcomes. As the burden of end-stage kidney disease (ESKD) has increased globally, there has also been a growing recognition of the importance of patient involvement in determining the goals of care and decisions regarding treatment. In January 2018, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference focused on dialysis initiation, including modality choice, access, and prescription. Here we present a summary of the conference discussions, including identified knowledge gaps, areas of controversy, and priorities for research. A major novel theme represented during the conference was the need to move away from a \u201cone-size-fits-all\u201d approach to dialysis and provide more individualized care that incorporates patient goals and preferences while still maintaining best practices for quality and safety. Identifying and including patient-centered goals that can be validated as quality indicators in the context of diverse health care systems to achieve equity of outcomes will require alignment of goals and incentives between patients, providers, regulators, and payers that will vary across health care jurisdictions

The European Renal Association - European Dialysis and Transplant Association Registry Annual Report 2014 : a summary

Background: This article summarizes the European Renal Association - European Dialysis and Transplant Association Registry's 2014 annual report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2014 within 35 countries. Methods: In 2016, the ERA-EDTA Registry received data on patients who in 2014 where undergoing RRT for ESRD, from 51 national or regional renal registries. Thirty-two registries provided individual patient level data and 19 provided aggregated patient level data. The incidence, prevalence and survival probabilities of these patients were determined. Results: In 2014, 70 953 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 133 per million population (pmp). The incidence ranged by 10-fold; from 23 pmp in the Ukraine to 237 pmp in Portugal. Of the patients commencing RRT, almost two-thirds were men, over half were aged >= 65 years and a quarter had diabetes mellitus as their primary renal diagnosis. By day 91 of commencing RRT, 81% of patients were receiving haemodialysis. On 31 December 2014, 490 743 individuals were receiving RRT for ESRD, equating to an unadjusted prevalence of 924 pmp. This ranged throughout Europe by more than 10-fold, from 157 pmp in the Ukraine to 1794 pmp in Portugal. In 2014, 19 406 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 36 pmp. Again this varied considerably throughout Europe. For patients commencing RRT during 2005-09, the 5-year-adjusted patient survival probabilities on all RRT modalities was 63.3% (95% confidence interval 63.0-63.6). The expected remaining lifetime of a 20-to 24-year-old patient with ESRD receiving dialysis or living with a kidney transplant was 21.9 and 44.0 years, respectively. This was substantially lower than the 61.8 years of expected remaining lifetime of a 20-year-old patient without ESRD.Peer reviewe