Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare condition attributed to plasma cell proliferation and the deposition of immunoglobulin light chains in the skin without association ...with systemic amyloidosis or hematological dyscrasias. It is not uncommon for patients diagnosed with PLCNA to also suffer from other auto-immune connective tissue diseases, with Sjögren's syndrome (SjS) showing the strongest association. This article provides a literature review and descriptive analysis to better understand the unique relationship between these two entities. To date, 34 patients with PLCNA and SjS have been reported in a total of 26 articles. The co-existence of PLCNA and SjS has been reported, especially in female patients in their seventh decade of life with nodular lesions on the trunk and/or lower extremities. Acral and facial localization, which is a typical localization of PLCNA in the absence of SjS, seems to be much more unusual in patients with associated SjS.
Type III Bartter syndrome (BS) is an autosomal recessive renal tubule disorder caused by loss-of-function mutations in the CLCNKB gene, which encodes the chloride channel protein ClC-Kb. In this ...study, we carried out a complete clinical and genetic characterization in a cohort of 30 patients, one of the largest series described. By comparing with other published populations, and considering that 80% of our patients presented the p.Ala204Thr Spanish founder mutation presumably associated with a common phenotype, we aimed to test the hypothesis that allelic differences could explain the wide phenotypic variability observed in patients with type III BS.
Clinical data were retrieved from the referral centers. The exon regions and flanking intronic sequences of the CLCNKB gene were screened for mutations by polymerase chain reaction (PCR) followed by direct Sanger sequencing. Presence of gross deletions or duplications in the region was checked for by MLPA and QMPSF analyses.
Polyuria, polydipsia and dehydration were the main common symptoms. Metabolic alkalosis and hypokalemia of renal origin were detected in all patients at diagnosis. Calciuria levels were variable: hypercalciuria was detected in 31% of patients, while 23% had hypocalciuria. Nephrocalcinosis was diagnosed in 20% of the cohort. Two novel CLCNKB mutations were identified: a small homozygous deletion (c.753delG) in one patient and a small deletion (c.1026delC) in another. The latter was present in compound heterozygosis with the already previously described p.Glu442Gly mutation. No phenotypic association was obtained regarding the genotype.
A poor correlation was found between a specific type of mutation in the CLCNKB gene and type III BS phenotype. Importantly, two CLCNKB mutations not previously described were found in our cohort.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tropical dry forests (TDF) are known to be resource‐limited due to a marked seasonality in precipitation. However, TDF are also shaped by factors such as solar radiation, wind speed, soil fertility, ...and land‐cover transformation. Together, these factors may determine different gradients of environmental harshness that are likely to drive changes in plant community attributes. Here, we evaluated the effects of environmental harshness on plant community diversity and structure of Colombian TDF, based on floristic and environmental data from 15 1‐ha permanent plots. We also analyzed these effects on legumes species only (including both deciduous and non‐deciduous species), deciduous species only (including both legumes and non‐legumes species), and on the whole community excluding either legumes or deciduous separately. Drier conditions and higher land‐cover transformation had the strongest negative effects on species diversity, basal area (BA), and canopy height. Soil fertility, on the contrary, did not have a significant effect on any of the evaluated response variables. Interestingly, legumes maintained their diversity and BA along the climatic gradient, while deciduous species were negatively affected by drier conditions and by an increase in secondary vegetation at the landscape level. Our results suggest that although TDF are limited by water availability, land‐cover transformation strongly increases environmental harshness. Yet, both legumes and deciduous species were differentially impacted by climatic and land transformation variables. Thus, to better understand TDF plant community attributes, it is necessary to consider these gradients and to disentangle their effects on different plant functional groups.
in Spanish is available with online material.
Resumen
Es ampliamente conocido que los bosques secos tropicales (BST) tienen fuertes limitaciones de recursos derivadas de estacionalidad de la precipitación. Sin embargo, otros factores como la radiación solar, la velocidad del viento, la fertilidad de los suelos y la transformación de las coberturas también dan forma a las condiciones ambientales restrictivas de este ecosistema. En conjunto, estos factores determinan la dureza ambiental que rige el BST y probablemente explican los cambios en los atributos comunitarios de las plantas a lo largo de gradientes. Evaluamos los efectos de la dureza ambiental sobre la diversidad de plantas y atributos estructurales del BST con base en datos florísticos y ambientales para 15 parcelas permanentes de 1 ha, para toda la comunidad de plantas, y subgrupos de plantas que incluyeron solo especies de leguminas y solo caducifolias por separado. Las condiciones secas y coberturas altamente transformadas tuvieron los efectos negativos sobre la diversidad de especies, el área basal y la altura del dosel a nivel comunitario, mientras que la fertilidad del suelo no afectó a ninguno de los atributos evaluados. Interesantemente, el grupo de especies leguminosas mantuvieron su diversidad y área basal a lo largo del gradiente de severidad climática, mientras que el grupo de especies de hoja caduca se vio negativamente afectado por las condiciones más secas y el aumento en el área de coberturas secundarias. Nuestros resultados sugieren que, aunque el BST esta claramente limitado por la disponibilidad del agua, la transformación de las coberturas naturales impulsa el aumento de la dureza ambiental en este ecosistema. Donde, las especies de leguminosas y caducifolias se ven afectadas de manera diferente a toda la comunidad de plantas. De tal forma, para un mejor entendimiento de como cambian los atributos comunitarios de las plantas en los BST es necesario tener en cuenta todas las fuentes de variación ambiental, así como, desagregar los efectos particulares para determinados grupos funcionales de plantas.
The disorders in the metabolism of calcium can present with manifestations that strongly suggest their diagnosis; however, most of the time, the symptoms with which they are expressed are nonspecific ...or present only as a laboratory finding, usually hypercalcemia. Because many of these disorders have a genetic etiology, in the present study, we sequenced a selection of 55 genes encoding the principal proteins involved in the regulation of calcium metabolism.
A cohort of 79 patients with hypercalcemia were analyzed by next-generation sequencing.
The 30% of our cohort presented one pathogenic or likely pathogenic variant in genes associated with hypercalcemia. We confirmed the clinical diagnosis of 17 patients with hypocalciuric hypercalcemia (pathogenic or likely pathogenic variants in the
and
genes), one patient with neonatal hyperparathyroidism (homozygous pathogenic variant in the
gene), and another patient with infantile hypercalcemia (two pathogenic variants in compound heterozygous state in the
gene). However, we also found variants in genes associated with primary hyperparathyroidism (
), renal hypophosphatemia with or without rickets (
,
,
,
, and
), DiGeorge syndrome (
and
), and hypophosphatasia (
). Our genetic study revealed 11 novel variants.
Our study demonstrates the importance of genetic analysis through massive sequencing to obtain a clinical diagnosis of certainty. The identification of patients with a genetic cause is important for the appropriate treatment and identification of family members at risk of the disease.
Tropical dry forests (TDFs) have been defined as a single biome occurring mostly in the lowlands where there is a marked period of drought during the year. In the Neotropics, dry forests occur across ...contrasting biogeographical regions that contain high beta diversity and endemism, but also strong anthropogenic pressures that threaten their biodiversity and ecological integrity. In Colombia, TDFs occur across six regions with contrasting soils, climate, and anthropogenic pressures, therefore being ideal for studying how these variables relate to dry forest species composition, successional stage and conservation status. Here, we explore the variation in climate and soil conditions, floristic composition, forest fragment size and shape, successional stage and anthropogenic pressures in 571 dry forest fragments across Colombia. We found that TDFs should not be classified solely on rainfall seasonality, as high variation in precipitation and temperature were correlated with soil characteristics. In fact, based on environmental factors and floristic composition, the dry forests of Colombia are clustered in three distinctive groups, with high species turnover across and within regions, as reported for other TDF regions of the Neotropics. Widely distributed TDF species were found to be generalists favored by forest disturbance and the early successional stages of dry forests. On the other hand, TDF fragments were not only small in size, but highly irregular in shape in all regions, and comprising mostly early and intermediate successional stages, with very little mature forest left at the national level. At all sites, we detected at least seven anthropogenic disturbances with agriculture, cattle ranching and human infrastructure being the most pressing disturbances throughout the country. Thus, although environmental factors and floristic composition of dry forests vary across regions at the national level, dry forests are equally threatened by deforestation, degradation and anthropogenic pressures all over the country, making TDFs a top priority for conservation in Colombia.
Androgenetic alopecia (AGA) is an androgen-dependent process and represents the most frequent non-scarring alopecia. Treatments for AGA do not always achieve a satisfactory result for the patient, ...and sometimes cause side effects that lead to discontinuation of treatment. AGA therapeutics currently includes topical and oral drugs, as well as follicular unit micro-transplantation techniques. Tissue engineering (TE) is postulated as one of the possible future solutions to the problem and aims to develop fully functional hair follicles that maintain their cyclic rhythm in a physiological manner. However, despite its great potential, reconstitution of fully functional hair follicles is still a challenge to overcome and the knowledge gained of the key processes in hair follicle morphogenesis and biology has not yet been translated into effective replacement therapies in clinical practice. To achieve this, it is necessary to research and develop new approaches, techniques and biomaterials. In this review, present and emerging hair follicle bioengineering strategies are evaluated. The current problems of these bioengineering techniques are discussed, as well as the advantages and disadvantages, and the future prospects for the field of TE and successful hair follicle regeneration.
Familial neurohypophyseal diabetes insipidus is a rare disease produced by a deficiency in the secretion of antidiuretic hormone and is caused by mutations in the arginine vasopressin gene.
Clinical, ...biochemical, and genetic characterization of a group of patients clinically diagnosed with familial neurohypophyseal diabetes insipidus, 1 of the largest cohorts of patients with protein neurophysin II (AVP-NPII) gene alterations studied so far.
The AVP-NPII gene was screened for mutations by PCR followed by direct Sanger sequencing in 15 different unrelated families from Spain.
The 15 probands presented with polyuria and polydipsia as the most important symptoms at the time of diagnosis. In these patients, the disease was diagnosed at a median of 6 years of age. We observed 11 likely pathogenic variants. Importantly, 4 of the AVP-NPII variants were novel (p.(Tyr21Cys), p.(Gly45Ser), p.(Cys75Tyr), p.(Gly88Cys)).
Cytotoxicity seems to be due to consequences common to all the variants found in our cohort, which are not able to fold correctly and pass the quality control of the ER. In concordance, we found autosomal dominant familial neurohypophyseal diabetes insipidus in the 15 families studied.
The aim of this study was to estimate the incidence of diabetes mellitus in the Basque Country and the risk factors involved in the disease by reassessing an adult population after 7 years of ...follow-up. In the previous prevalence study, 847 people older than 18 years were randomly selected from all over the Basque Country and were invited to answer a medical questionnaire, followed by a physical examination and an oral glucose tolerance test. In the reassessment, the same variables were collected and the resulting cohort comprised 517 individuals of whom 43 had diabetes at baseline. The cumulative incidence of diabetes was 4.64% in 7 years and the raw incidence rate was 6.56 cases/1000 person-years (95%CI: 4.11-9.93). Among the incident cases, 59% were undiagnosed. The most strongly associated markers by univariate analyses were age > 60 years, dyslipidaemia, prediabetes and insulin resistance. We also found association with hypertension, obesity, family history of diabetes and low education level. Multivariate analysis adjusted for age and sex showed that a set of risk factors assessed together (dyslipidaemia, waist-to-hip-ratio and family history of diabetes) had great predictive value (AUC-ROC = 0.899, 95%CI: 0.846-0.953, p = 0.942), which suggests the need for early intervention before the onset of prediabetes.
Background
Primary distal renal tubular acidosis (dRTA) is a rare genetic disorder caused by impaired distal mechanisms of urinary acidification. Most cases are secondary to pathogenic variants in
...ATP6V0A4
,
ATP6V1B1
, and
SLC4A1
genes, which encode transporters regulating acid-base balance in the collecting duct.
Methods
Retrospective study of molecular and clinical data from diagnosis and long-term follow-up (10, 20, and 40±10 years) of 16 patients with primary dRTA diagnosed in childhood.
Results
Molecular analyses revealed nine patients had
ATP6V0A4
pathogenic variants, five in
ATP6V1B1
, and two in
SLC4A1
. A novel intragenic deletion and a common
ATP6V0A4
gene variant (c.1691 + 2dupT) in
ATP6V0A4
occurred in two-thirds of these patients, suggesting a founder effect. Median age at diagnosis was 3.25 months (IQR 1, 13.5), which was higher in the
SLC4A1
group. Median SDS height at diagnosis was −1.02 (IQR −1.79, 0.14). Delayed clinical diagnosis was significantly related to growth failure (
P
= 0.01). Median SDS height at 20 years follow-up was −1.23 (IQR −1.71, −0.48), and did not significantly improve from diagnosis (P = 0.76). Kidney function declined over time: at last follow-up, 43% had moderate to severe chronic kidney disease (CKD). Adequate metabolic control was not related to CKD development. Incidence of sensorineural hearing loss (SNHL) was high in
ATP6V1B1
patients, though not universal. Patients harboring
ATP6V0A4
variants also developed SNHL at a high rate (80%) over time.
Conclusions
Patients with dRTA can develop moderate to severe CKD over time with a high frequency despite adequate metabolic control. Early diagnosis ameliorates long-term height prognosis.
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