Danon disease is a severe multisystem disorder clinically characterized by hypertrophic cardiomyopathy, skeletal myopathy and mental retardation in male patients, and by a milder phenotype ...(predominantly involving cardiac muscle) in female patients. The disease is inherited as an X‐linked dominant trait. The primary deficiency of lysosome‐associated membrane protein‐2 (LAMP‐2) causes disruption of autophagy, leading to an impaired fusion of lysosomes to autophagosomes and biogenesis of lysosomes. We surveyed over 500 Danon disease patients reported in the literature from the first description to the present, in order to summarize the clinical, pathological and molecular data and treatment perspectives. An early molecular diagnosis is of crucial importance for genetic counselling and for therapeutic interventions: in male patients, the prognosis is poor due to rapid progression towards heart failure, and only heart transplantation modifies the disease course.
Human aging results in a variety of changes to skeletal muscle. Sarcopenia is the age-associated loss of muscle mass and is one of the main contributors to musculoskeletal impairments in the elderly. ...Previous research has demonstrated that resistance training can attenuate skeletal muscle function deficits in older adults, however few articles have focused on the effects of resistance training on functional mobility. The purpose of this systematic review was to 1) present the current state of literature regarding the effects of resistance training on functional mobility outcomes for older adults with skeletal muscle function deficits and 2) provide clinicians with practical guidelines that can be used with seniors during resistance training, or to encourage exercise. We set forth evidence that resistance training can attenuate age-related changes in functional mobility, including improvements in gait speed, static and dynamic balance, and fall risk reduction. Older adults should be encouraged to participate in progressive resistance training activities, and should be admonished to move along a continuum of exercise from immobility, toward the recommended daily amounts of activity.
Background and Objectives
One of the pathogenetic hypotheses of delirium is the “neuroinflammatory theory” with consequent neurotoxicity of brain connectivity networks. Micronutrients may play a ...significant role in the prevention of neuroinflammation. This systematic review addresses the role of micronutrients in the development of delirium in older populations.
Methods
The EBSCO, Cochrane, PubMed, and Web of Science databases were searched for articles on delirium and micronutrients. The methodological quality of the studies included in the review was evaluated with the Newcastle-Ottawa Scales for observational studies and for case-control studies.
Results
1326 papers were identified from the searches, 7 of which met the inclusion criteria (see section 2.3). All the papers included were written in English. Delirium was predominantly secondary to post-operative dysfunction or acute medical conditions. By altering the production of neurotransmitters resulting in an imbalance, and by reducing their immunomodulatory role with a consequent increase in inflammatory oxidative stress, micronutrient deficiency seems to be associated with an increased incidence of delirium.
Conclusions
This review supports the existence of an association between micronutrient deficiency (i.e. cobalamin, thiamine, and vitamin D) and an increased incidence of delirium, with a greater prevalence in hospitalized patients.
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•Novel combination of close proximity and room-scale risk assessment approaches.•Prediction of contagious risk due to SARS-CoV-2 respiratory infection in buses.•For urban buses the ...close proximity significantly affects the reproductive number.•For long-distance buses a full occupancy of the bus can hardly be maintained.•Appropriate filtration of recirculated air and FFP2 masks permit full occupancy.
Public transport environments are thought to play a key role in the spread of SARS-CoV-2 worldwide. Indeed, high crowding indexes (i.e. high numbers of people relative to the vehicle size), inadequate clean air supply, and frequent extended exposure durations make transport environments potential hotspots for transmission of respiratory infections. During the COVID-19 pandemic, generic mitigation measures (e.g. physical distancing) have been applied without also considering the airborne transmission route. This is due to the lack of quantified data about airborne contagion risk in transport environments.
In this study, we apply a novel combination of close proximity and room-scale risk assessment approaches for people sharing public transport environments to predict their contagion risk due to SARS-CoV-2 respiratory infection. In particular, the individual infection risk of susceptible subjects and the transmissibility of SARS-CoV-2 (expressed through the reproduction number) are evaluated for two types of buses, differing in terms of exposure time and crowding index: urban and long-distance buses. Infection risk and reproduction number are calculated for different scenarios as a function of the ventilation rates (both measured and estimated according to standards), crowding indexes, and travel times. The results show that for urban buses, the close proximity contribution significantly affects the maximum occupancy to maintain a reproductive number of <1. In particular, full occupancy of the bus would be permitted only for an infected subject breathing, whereas for an infected subject speaking, masking would be required. For long-distance buses, full occupancy of the bus can be maintained only if specific mitigation solutions are simultaneously applied. For example, for an infected person speaking for 1 h, appropriate filtration of the recirculated air and simultaneous use of FFP2 masks would permit full occupancy of the bus for a period of almost 8 h. Otherwise, a high percentage of immunized persons (>80%) would be needed.
Update on polyglucosan storage diseases Cenacchi, Giovanna; Papa, V.; Costa, R. ...
Virchows Archiv : an international journal of pathology,
12/2019, Letnik:
475, Številka:
6
Journal Article
Recenzirano
An abnormal structural form of glycogen (with less branching points or amylopectin-like polysaccharide) called polyglucosan (PG) may accumulate in various tissues such as striated and smooth muscles, ...brain, nerve, liver and skin, and cause a group of nine different genetic disorders manifesting with a variety of clinical phenotypes that affect mainly the nervous system (Lafora disease, adult PG body disease), the heart (glycogen storage disease type XV, hypertrophic cardiomyopathy type 6, PG body myopathy type 1) and the skeletal muscle (glycogen storage disease type IV, glycogen storage disease type VII, PG body myopathy type 2), depending on the organs which are mostly affected by the PG aggregates. The pathological feature of PG storage in tissues is a hallmark of these disorders. Whole-genome sequencing has allowed to obtain a diagnosis in a large number of patients with a previously unrecognized disorder. We describe the clinical, pathological and molecular features of these genetic disorders, for many of which the pathological mechanisms underlying the corresponding mutant gene have been investigated and, at least in part, understood.
Recognized since antiquity, gout is still a relevant pathology with rising prevalence and incidence. This study aims to assess the reference accuracy in journal articles mentioning the early use of ...the word ‘gout’. Specifically, it investigates whether the term was indeed coined in the 13th century by the Dominican monk Randolphus of Bocking, as widely believed. Several historical sources in their original Latin were consulted to test the hypothesis of literary mentions predating Randolphus of Bocking’s description. At the same time, biomedical articles spanning the last two decades were perused using specific keywords in different combinations to determine the accuracy level of references related to the earliest use of the word ‘gout’. The results showed that several biomedical publications wrongly ascribed the origin of the word ‘gout’ to Randolphus of Bocking. Indeed, various texts predate his mention by many years. In particular, gutta, the Latin word used to indicate a host of rheumatological conditions including gout, is recorded as early as the 10th century in a biography dedicated to the martyred nun Saint Wiborada of St. Gall. Written by Swiss monks between AD 960 and 963, this text should be regarded as containing the earliest known adoption of the word. For this reason, scholars should now avoid quoting Randolph of Bocking’s description as the first use of the word ‘gout’ in Western literature.
Polymers are extensively used for the realization of drug delivery systems across multiple scales, from nanomedicines to microparticles and macroscopic implantable devices, for their favorable ...biodegradation profiles and tunable physicochemical features. The accurate quantification of the polymer content is key to finely controlling drug loading and release and ensuring reproducibility, yet it continues to be a major challenge in the design and development of delivery systems. In this study, we introduce a novel protocol based on the PULCON technique to quantify, with a routine NMR spectroscopy analysis, the precise concentration of polymers in various delivery systems. Specifically, the PULCON protocol is applied to characterize the physicochemical and pharmaceutical properties of nanoparticles, microparticles, and implantable devices realized by combining three extensively used polymers, namely, poly(lactic-co-glycolic acid) (PLGA), poly(vinyl alcohol) (PVA), and poly(ethylene glycol) (PEG). Without using internal calibration procedures, in a single step, the PULCON protocol precisely quantifies the concentration of each polymer and the drug content. This approach can be readily implemented on standard NMR spectrometers, enabling accurate characterization of drug delivery systems and facilitating their effective development.
Introduction
The growing demographic presence of the transgender (TGD) population has sparked an increase in clinical investigations focusing on the impacts of gender-affirming hormone therapy (GAHT) ...in adults with gender dysphoria. Despite this surge in studies, there remains a significant gap in the literature regarding the health status of older TGD individuals. This review aims to assess prevalent pathological conditions within the TGD population, specifically concentrating on aging-related diseases investigated to date.
Methods
A systematic search across Embase Ovid, Scopus, PubMed, Cochrane Library, and Web of Science databases was conducted to identify articles reporting on the aging process in TGD individuals. Methodological quality was evaluated using Newcastle–Ottawa Scale (NOS) scores.
Results
Initial database searches yielded 12,688 studies, which were refined to 18 through elimination of duplicates and title/abstract review. Following a comprehensive appraisal, nine studies were included in the systematic review. These articles, published between 2017 and 2023, involved a total of 5403 participants. The evidence indicates a noteworthy percentage of the TGD population being at risk for cardiovascular diseases, experiencing depression or disability, and demonstrating hesitancy toward major recommended screening programs.
Conclusions
Limited studies on older TGD individuals highlight not only an organic risk of chronic diseases but also a cognitive/psychiatric risk that should not be underestimated. Further research is imperative to deepen our understanding of the pathophysiological mechanisms involved in the health challenges faced by older TGD individuals.
Dentinal proteases are believed to play an important role in the degradation of hybrid layers (HL). This study investigated the HL gelatinolytic activity by in situ zymography and functional enzyme ...activity assay. The hypotheses were that HLs created by an etch-and-rinse adhesive exhibit active gelatinolytic activity, and MMP-2 and -9 activities in dentin increase during adhesive procedures. Etched-dentin specimens were bonded with Adper Scotchbond 1XT and restored with composite. Adhesive/dentin interface slices were placed on microscope slides, covered with fluorescein-conjugated gelatin, and observed with a multi-photon confocal microscope after 24 hrs. Human dentin powder aliquots were prepared and assigned to the following treatments: A, untreated; B, etched with 10% phosphoric acid; or C, etched with 10% phosphoric acid and mixed with Scotchbond 1XT. The MMP-2 and -9 activities of extracts of dentin powder were measured with functional enzyme assays. Intense and continuous enzyme activity was detected at the bottom of the HL, while that activity was more irregular in the upper HL. Both acid-etching and subsequent adhesive application significantly increased MMP-2 and -9 activities (p < 0.05). The results demonstrate, for the first time, intrinsic MMP activity in the HL, and intense activation of matrix-bound MMP activity with both etching and adhesive application.
Summary
Background
While several commercial dermoepidermal scaffolds can promote wound healing of the skin, the achievement of complete skin regeneration still represents a major challenge.
...Objectives
To perform biological characterization of self‐assembled extracellular matrices (ECMs) from three different subpopulations of fibroblasts found in human skin: papillary fibroblasts (Pfi), reticular fibroblasts (Rfi) and dermal papilla fibroblasts (DPfi).
Methods
Fibroblast subpopulations were cultured with ascorbic acid to promote cell‐assembled matrix production for 10 days. Subsequently, cells were removed and the remaining matrices characterized. Additionally, in another experiment, keratinocytes were seeded on the top of cell‐depleted ECMs to generate epidermal‐only skin constructs.
Results
We found that the ECM self‐assembled by Pfi exhibited randomly oriented fibres associated with the highest interfibrillar space, reflecting ECM characteristics that are physiologically present within the papillary dermis. Mass spectrometry followed by validation with immunofluorescence analysis showed that thrombospondin 1 is preferentially expressed within the DPfi‐derived matrix. Moreover, we observed that epidermal constructs grown on DPfi or Pfi matrices exhibited normal basement membrane formation, whereas Rfi matrices were unable to support membrane formation.
Conclusions
We argue that inspiration can be taken from these different ECMs, to improve the design of therapeutic biomaterials in skin engineering applications.
What's already known about this topic?
There are several types of skin fibroblasts within the dermis that can be defined by their spatial location: papillary fibroblasts (Pfi), reticular fibroblasts (Rfi) and dermal papilla fibroblasts (DPfi).
Extracellular matrix (ECM) composition is distinct with regard to composition and architecture within the papillary, reticular and hair follicle dermis in vivo.
When skin is injured, dermal replacement substitutes used for tissue repair do not reflect the heterogeneity observed within the skin dermis.
What does this study add?
Self‐assembled ECMs from different subpopulations of skin fibroblasts can be generated in vitro.
Cell‐assembled ECMs made in vitro from Pfi, Rfi and DPfi reflect dermal heterogeneity seen in vivo and are morphologically, functionally and compositionally distinct from one another.
Inspiration should be taken from cell‐assembled ECMs from distinct fibroblast subpopulations, to improve the design of therapeutic biomaterials in skin engineering applications.
What is the translational message?
Cell‐assembled ECMs from DPfi and Pfi, but not Rfi, can support formation of a basement membrane in adjacent keratinocytes in vitro.
Inspiration should be taken from cell‐assembled ECMs from distinct fibroblast subpopulations, to improve the design of therapeutic biomaterials in skin engineering applications.
Linked Comment: Mellody et al. Br J Dermatol 2018; 179:248–250.
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