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1.
Diagnostics (Basel) ; 14(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38732345

RESUMO

Infectious diseases account for about 3 million deaths per year. The advent of molecular techniques has led to an enormous improvement in their diagnosis, both in terms of sensitivity and specificity and in terms of the speed with which a clinically useful result can be obtained. Digital PCR, or 3rd generation PCR, is based on a series of technical modifications that result in more sensitive techniques, more resistant to the action of inhibitors and capable of direct quantification without the need for standard curves. This review presents the main applications that have been developed for the diagnosis of viral, bacterial, and parasitic infections and the potential prospects for the clinical use of this technology.

2.
J Chem Inf Model ; 64(9): 3855-3864, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38623052

RESUMO

Allosteric modulation plays a critical role in enzyme functionality and requires a deep understanding of the interactions between the active and allosteric sites. γ-Secretase (GS) is a key therapeutic target in the treatment of Alzheimer's disease (AD), through its role in the synthesis of amyloid ß peptides that accumulate in AD patients. This study explores the structure and dynamic effects of GS modulation by E2012 binding, employing well-tempered metadynamics and conventional molecular dynamics simulations across three binding scenarios: (1) GS enzyme with and without L458 inhibitor, (2) the GS-substrate complex together with the modulator E2012 in two different binding modes, and (3) E2012 interacting with a C99 substrate fragment. Our findings reveal that the presence of L458 induces conformational changes that contribute to stabilization of the GS enzyme dynamics, previously reported as a key factor that allowed the resolution of the cryo-EM structure and the enhanced binding of E2012. Furthermore, we identified the most favorable binding site for E2012 within the GS-substrate complex, uncovering significant modulatory effects and a complex network of interactions that influence the position of the substrate for catalysis. In addition, we explore a potential substrate-modulator binding before the formation of the enzyme-substrate complex. The insights gained from our study emphasize the importance of these interactions in the development of potential therapeutic interventions that target the functionality of the GS enzyme in AD.


Assuntos
Alanina/análogos & derivados , Secretases da Proteína Precursora do Amiloide , Simulação de Dinâmica Molecular , Ligação Proteica , Secretases da Proteína Precursora do Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/química , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Especificidade por Substrato , Humanos , Conformação Proteica , Regulação Alostérica/efeitos dos fármacos , Azepinas
3.
J Clin Med ; 13(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38610864

RESUMO

Background: The aim of this study was to evaluate patients' knowledge and perceptions of the use of systemic antibiotics in the treatment of endodontic infections and to determine the possible contribution of patients to the development of bacterial resistance. Methods: A total of 550 patients were asked to respond to a survey on the perception of systemic antibiotic use in the treatment of endodontic infections and antibiotic resistance during January 2022 and March 2023. A bivariate and multivariate analysis was performed to determine possible correlates in the population regarding antibiotic use in the endodontic world. Results: A total of 514 patients were included in the study, 65.9% of whom were women. While 34.6% of the population studied thought that it was always necessary to take antibiotics prior to endodontics, 49.4% considered that they were necessary after endodontics, regardless of the clinical symptoms. The prevalence of self-medication was 17.3%, and women self-medicate more than men, with significant differences (p < 0.05), although they have a greater knowledge of antibiotic resistance than men (p < 0.05). Forty-four percent of the population expected to take antibiotics when faced with dental pain, mainly women (p < 0.05). Conclusions: The general population is contributing to the serious problem of bacterial resistance. It is necessary to promote educational strategies focused on the correct use of antibiotics in the community. The worst results were found mainly in the population with a low level of education. The level of education was the variable that most influenced the knowledge and attitudes of the population, followed by the sex of the participants.

4.
BMJ Open ; 14(2): e072784, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355186

RESUMO

BACKGROUND: A paucity of predictive models assessing risk factors for COVID-19 mortality that extend beyond age and gender in Latino population is evident in the current academic literature. OBJECTIVES: To determine the associated factors with mortality, in addition to age and sex during the first year of the pandemic. DESIGN: A case-control study with retrospective revision of clinical and paraclinical variables by systematic revision of clinical records was conducted. Multiple imputations by chained equation were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalisation. No intervention was performed. SETTING: High-complexity centre above 2640 m above sea level (masl) in Colombia. PARTICIPANTS: A population sample of 564 patients admitted to the hospital with confirmed COVID-19 by PCR. Deceased patients (n=282) and a control group (n=282), matched by age, sex and month of admission, were included. MAIN OUTCOME MEASURE: Mortality during hospitalisation. MAIN RESULTS: After the imputation of datasets, CART analysis estimated 11 clinical profiles based on respiratory distress, haemoglobin, lactate dehydrogenase, partial pressure of oxygen to inspired partial pressure of oxygen ratio, chronic kidney disease, ferritin, creatinine and leucocytes on admission. The accuracy model for prediction was 80.4% (95% CI 71.8% to 87.3%), with an area under the curve of 78.8% (95% CI 69.63% to 87.93%). CONCLUSIONS: This study discloses new interactions between clinical and paraclinical features beyond age and sex influencing mortality in COVID-19 patients. Furthermore, the predictive model could offer new clues for the personalised management of this condition in clinical settings.


Assuntos
COVID-19 , Humanos , Estudos de Casos e Controles , SARS-CoV-2 , Estudos Retrospectivos , Oxigênio , Mortalidade Hospitalar
5.
Aesthet Surg J ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38366902

RESUMO

Liposuction is considered one of the most common procedures in plastic surgery. However, major postoperative complications such as visceral injury, fluid overload, and necrotizing fasciitis still occur. Likewise, minor complications such as ecchymosis, seromas, infections, and contour irregularities that do not threaten the life of the patient do generate significant dissatisfaction. Current evidence regarding the management of fibrosis after previous liposuction remains limited. The objective of this article is to standardize a management algorithm based on the extensive experience and successful results of the primary author. Patients who underwent secondary liposculpture between August 2022 and May 2023 were evaluated prospectively. Inclusion criteria: Women between 18 and 60 years, non-smokers, with a body mass index (BMI) <35 kg/m2, history of previous body contouring surgeries. Identification of the patient's skin condition and subcutaneous lesions in the adipose tissue were obtained in detail. Statistical analysis of preoperative and postoperative medical photographs was also performed with Fiji Biological image analyzer. Photographic analysis showed a statistically significant difference between the areas affected by fibrosis from the preoperative photos compared to that from the postoperative ones (p<.001). The most frequent clinical findings were depressions in 99% of the women (74), followed by soft nodules in 95% (70), hard nodules in 81% (61), adherences in 47% (35), and finally, cutaneous bursas in 4%. Our classification system and management algorithm for fibrosis and contour irregularities is a safe and reliable tool and results were objectively verified, yielding statistically significant outcomes.

6.
Ann Otol Rhinol Laryngol ; 133(2): 174-180, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37608685

RESUMO

OBJECTIVE: Superior laryngeal nerve (SLN) block consists of injection of steroid and anesthetic at the internal branch of the SLN entry site. Prior case series have demonstrated beneficial effects on neurogenic cough. SLN blocks have also recently shown benefit for paralaryngeal pain. We describe short-term outcomes for multiple symptoms of irritable larynx syndrome (ILS) including neurogenic cough, dysphonia related to laryngeal hypersensitivity, inducible laryngeal obstruction (ILO), paralaryngeal pain, and isolated globus. METHODS: Retrospective review from 2 institutions of patients undergoing a single SLN block for the indications listed. Variables include age, sex, indication(s), known vagus neuropathy, and patient-reported outcomes at short-term follow-up. RESULTS: A total of 209 patients were included (59 males, 150 females; age: 58 ± 13 years). Twenty-six patients (12%) had a history of a vagus nerve injury. Indications included neurogenic cough (n = 149), dysphonia related to laryngeal hypersensitivity (n = 66), paralaryngeal pain (n = 50), ILO (n = 23), and isolated globus (n = 3). Some patients had multiple indications. Significant improvements in patient-reported measures occurred after a single SLN block within 2 to 4 weeks for neurogenic cough (cough severity index; 25.2 ± 11.2 to 19.0 ± 12.8; P < .001), dysphonia (voice handicap index-10; 22.1 ± 12.2-18.0 ± 13.3; P = .005), and ILO (dyspnea index; 21.0 ± 14.9-14.7 ± 15.7; P = .017). Subjective pain improved in 23 of 39 patients with paralaryngeal pain. There was no observed improvement for isolated globus. Presence of known vagal neuropathy or therapy around the time of SLN block did not affect outcome. CONCLUSION: SLN block can be an effective component of treatment for a variety of ILS symptoms. Patients may experience some improvement after 1 injection. LAY SUMMARY: Symptoms of irritable larynx syndrome, such as neurogenic cough, paralaryngeal pain, inducible laryngeal obstruction, and dysphonia related to laryngeal hypersensitivity can be challenging to manage. In-office Superior Laryngeal Nerve blocks can serve as a quick, well tolerated, adjunctive treatment with positive short-term outcomes. LEVEL OF EVIDENCE: 4.


Assuntos
Obstrução das Vias Respiratórias , Disfonia , Doenças da Laringe , Laringe , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Disfonia/diagnóstico , Disfonia/etiologia , Disfonia/terapia , Nervos Laríngeos , Tosse/etiologia , Tosse/terapia , Dor
7.
Pain ; 165(3): 537-549, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37870223

RESUMO

ABSTRACT: Neural mobilisations (NM) have been advocated for the treatment of nerve-related cervicobrachial pain; however, it is unclear what types of patients with nerve-related cervicobrachial pain (if any) may benefit. Medline, Web of Science, Scopus, PeDro, Cinahl, and Cochrane databases were searched from inception until December 2022. Randomised controlled trials were included if they assessed the effectiveness of NM in nerve-related cervicobrachial pain, and outcome measures were pain intensity and/or disability. Studies were classified according to their inclusion/exclusion criteria as radiculopathy , Wainner cluster , Hall , and Elvey cluster or other . Meta-analyses with subgroup analyses were performed. Risk of bias was assessed using Cochrane Rob2 tool. Twenty-seven studies were included. For pain and disability reduction, NM was found to be more effective than no treatment (pooled pain mean difference [MD] = -2.81, 95% confidence interval [CI] = -3.81 to -1.81; pooled disability standardized mean difference = -1.55, 95% CI = -2.72 to -0.37), increased the effectiveness of standard physiotherapy as an adjuvant when compared with standard physiotherapy alone (pooled pain MD = -1.44, 95% CI = -1.98 to -0.89; pooled disability MD = -11.07, 95% CI = -16.38 to -5.75) but was no more effective than cervical traction (pooled pain MD = -0.33, 95% CI = -1.35 to 0.68; pooled disability MD = -10.09, 95% CI = -21.89 to 1.81). For disability reduction, NM was found to be more effective than exercise (pooled MD = -18.27, 95% CI = -20.29 to -17.44). In most comparisons, there were significant differences in the effectiveness of NM between the subgroups. Neural mobilisations was consistently more effective than all alternative interventions (no treatment, traction, exercise, and standard physiotherapy alone) in 13 studies classified as Wainner cluster . PROSPERO registration: CRD42022376087.


Assuntos
Dor , Modalidades de Fisioterapia , Humanos
8.
Molecules ; 28(21)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37959689

RESUMO

Beyond their nutritional benefits, vitamins could decrease the risk of chronic diseases due to their potent antioxidant capacity. The present work is aimed at reviewing the state of the art regarding (1) the vitamins involved in oxidative stress prevention in accordance with the requirements established by the European Food Safety Authority (EFSA) and (2) the foods of plant origin that are sources of those vitamins and have potential benefits against oxidative stress in humans. According to the European regulations based on EFSA scientific evidence, riboflavin, vitamin C, and vitamin E are those vitamins subjected to the approved health claim "contribute to the protection of cells from oxidative stress". Scientific studies conducted in humans with some natural food sources of riboflavin (almonds, wheat germ, mushrooms, oat bran), vitamin C (guava, kale, black currant, Brussels sprouts, broccoli, orange), and vitamin E (hazelnuts, almonds, peanuts, pistachio nuts, extra virgin olive oil, dates, rye) have been performed and published in the literature. However, no food of plant origin has obtained a favorable EFSA opinion to substantiate the approval of health claims related to its potential properties related to oxidative stress prevention. Further studies (concretely, well-controlled human intervention studies) must be carried out in accordance with EFSA requirements to provide the highest level of scientific evidence that could demonstrate the potential relationship between foods of plant origin and antioxidant capacity. This review could be useful for the scientific community to study the application of health claims referring to the antioxidant capacity potentially exerted by foods of plant origin.


Assuntos
Antioxidantes , Vitaminas , Humanos , Vitaminas/farmacologia , Antioxidantes/farmacologia , Estresse Oxidativo , Inocuidade dos Alimentos , Vitamina A , Vitamina K , Vitamina E , Ácido Ascórbico , Riboflavina
9.
Nutrients ; 15(21)2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37960245

RESUMO

Micronutrients play a critical role in pregnant women, a vulnerable group with higher nutritional requirements. The first strategy to achieve adequate micronutrients intake should always be through a healthy and balanced diet. In the case where the diet is not enough to meet these requirements, food supplements should be prescribed under supervision to complement the diet, and these products must bear reliable information about the declared nutritional contents and health benefits. Based on the data provided by the Coordinated System of Fast Interchange of Information (SCIRI) and to know the current national situation, this work addresses the assessment of the content and the adequacy of health claims related to some micronutrients (vitamin C, vitamin B9, iron, copper, manganese, zinc, calcium, magnesium) contained in food supplements for pregnant women commercialized in Spain. Analytical results coincided with the declared values and were covered by the ranges of tolerances, and samples met the requirements to use health claims. Although the samples could even include more claims, manufacturers could have selected those which either best addressed pregnant women's conditions or best aligned with marketing intentions. This study confirms an adequate use of health claims in food supplement samples, which could be interesting for strengthening consumers' confidence in the benefits shown in the labeling and for encouraging the use of health claims as a useful tool for making better-informed purchasing decisions.


Assuntos
Micronutrientes , Gestantes , Humanos , Feminino , Gravidez , Suplementos Nutricionais , Dieta , Vitaminas , Necessidades Nutricionais
10.
mBio ; : e0282223, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38014993

RESUMO

IMPORTANCE: Mitochondria constitute major sources of H2O2 and other reactive oxygen species in eukaryotic cells. The division of these organelles is crucial for multiple processes in cell biology and relies on highly regulated mechano-GTPases that are oligomerization dependent and belong to the dynamin-related protein family, like A. nidulans DnmA. Our previous work demonstrated that H2O2 induces mitochondrial constriction, division, and remodeling of the outer membrane. Here, we show that H2O2 also induces a DnmA aggregation consistent with higher-order oligomerization and its recruitment to mitochondria. The study of this response uncovered that H2O2 induces the depolymerization and reorganization of actin as well as the critical role that cysteines 450 and 776 play in DnmA function. Our results provide new insights into the mechanisms of reactive oxygen species cell signaling and how they can regulate the dynamics of the actin cytoskeleton and the division of mitochondria and peroxisomes.

11.
J Mol Model ; 29(11): 352, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37906368

RESUMO

CONTEXT: 2,2,2-Trifluoroethanol has been widely used to study the structure and dynamic properties of intrinsically disordered proteins. Experimentally, it is known that TFE-water mixtures stabilize secondary structures of IDPs, and therefore, it allows the studying of conformational ensembles of these proteins. In the last decades, molecular dynamic simulations have helped study the IDPs' conformational ensemble. Unfortunately, conventional MD requires very long simulation times to describe the properties of IDPs. Therefore, a variety of accelerated sampling techniques have been developed and employed. The TFE-water mixture arrangement description through MD has faced substantial difficulties since emulating the TFE nanocrowding at certain TFE:H[Formula: see text]O ratios (around 15-40% of TFE). In this work, we determine the most suitable conditions that reproduce experimentally reported properties of TFE-water mixtures. We compared the employment of conventional MD and GaMD simulations and various water parameters. Our results show that the combination of parameters that better reproduce the experimental information is the combination of the TIP4PD water model and GaMD simulations. Therefore, these conditions help accurately describe the structural ensemble of IDPs in TFE-water mixtures. METHODS: Conventional MD and GaMD simulations were performed under AMBER 18 software. The TFE and water molecules were described using GAFF2 and a variety of water models, such as TIP3P, TIP4P2005, TIP4PD, and TIP5P, respectively. The systems were simulated a 100 ns at 298 K.

12.
Proteins ; 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37455623

RESUMO

Protein-protein association events are involved in many physiological and pathological processes. Cataract disease is a pathology that manifests protein aggregation of crystallins. ß-Crystallins are present in a high proportion in the eye lens. Therefore, the structural study of the dimerization properties of crystallins can shed light on the first stages of protein aggregation. In the present work, we examine the protein-protein association profiles of the human ßB2-crystallin by employing extensive coarse-grained molecular dynamics (CG-MD) and the Markov state analysis. Interestingly, our results clearly show important changes in the protein dimerization kinetics between wt-HßB2C and the deamidated systems. The two systems show dimeric conformations. However, the association and dissociation rates are very different. Our results show that the deamidated system can associate faster and dissociate slower than the wt- HßB2C. The deamidated system is in a slightly opened conformation with the Greek-key motifs well folded, suggesting that a complete unfolding of the protein is not required for aggregation. Our results describe the first stages of crystallin aggregation due to post-translational modifications.

13.
Drugs R D ; 23(2): 185-195, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37318714

RESUMO

BACKGROUND: Nausea and vomiting is a very prevalent condition during pregnancy. Combination of doxylamine and pyridoxine is placed as first-line pharmacological option for its treatment in most clinical guidelines. Among different release forms available, Cariban® is a fixed-dose combination of doxylamine/pyridoxine 10/10 mg, formulated as modified-release capsules. OBJECTIVES: In the present study, we aimed to characterize the bioavailability performance of Cariban® in vitro and in vivo. METHODS: An in vitro dissolution test was performed to evaluate the release profile of Cariban®, together with immediate- and delayed-release formulations available on the market. A single-center, single-dose, open-label bioavailability study following Cariban® administration in 12 healthy adult female patients was carried out to explore the drug behavior in vivo (protocol NBR-002-13; EUDRA-CT 2013-005422-35). These data were additionally used to perform a computational pharmacokinetic simulation of the posology approved for this drug. RESULTS: Cariban® capsules demonstrate a prolonged-release performance, with an early, gradual, and progressive release of both actives until reaching a complete dissolution after 4-5 h in solution. The pharmacokinetic features of these capsules show that doxylamine and pyridoxine metabolites are early absorbed, being all detectable in plasma within 1 h following oral administration. Computational pharmacokinetic simulation predicts that different posology provides distinct profiles of metabolites in plasma, with 1-1-2 (morning-midafternoon-night) being the one that concentrates higher plasma levels but lower dose dumping for 24 h. CONCLUSION: Cariban® behaves as a prolonged-release formulation, which correlates with rapid absorption and arising of the actives in the plasma, but also long-lasting and sustained bioavailability, especially when administered following the complete posology. These results would underlie its demonstrated efficacy to relieve nausea and vomiting of pregnancy (NVP) under clinical settings.


Assuntos
Antieméticos , Complicações na Gravidez , Adulto , Feminino , Humanos , Gravidez , Antieméticos/farmacocinética , Antieméticos/uso terapêutico , Disponibilidade Biológica , Cápsulas , Preparações de Ação Retardada , Doxilamina/farmacocinética , Combinação de Medicamentos , Náusea , Complicações na Gravidez/tratamento farmacológico , Piridoxina/farmacocinética , Piridoxina/uso terapêutico , Vômito/tratamento farmacológico
14.
Retin Cases Brief Rep ; 17(4): 478-481, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37364213

RESUMO

BACKGROUND/PURPOSE: Optical coherence tomography angiography has been used to evaluate the posterior segment in a wide variety of pathologies because it is a noninvasive image technique, but its role in the evaluation of the retina in a case of carotid cavernous sinus fistula has not been described yet. METHODS RESULTS: We present a patient who consulted with spontaneous left superior eyelid hematoma and was diagnosed with left indirect carotid cavernous sinus fistula. In this study, optical coherence tomography angiography was used to evaluate the different macular capillary plexuses in a patient with carotid cavernous sinus fistula and a clinical situation of secondary local venous stasis before and after percutaneous embolization. Augmented vessel density was seen in superficial and deep capillary plexuses and in choriocapillaris before the percutaneous embolization, and a decrease of the parameters was seen after the treatment. CONCLUSION: All macular capillary plexuses presented with augmented vessel density levels that normalized after treatment. These findings were previously undescribed, and they suggest that optical coherence tomography angiography may be useful to initially evaluate patients with carotid cavernous sinus fistula who are planned to undergo embolization and to follow them up until normalization of the vascular structures is reported.


Assuntos
Fístula Carótido-Cavernosa , Embolização Terapêutica , Fístula , Humanos , Fístula Carótido-Cavernosa/diagnóstico , Fístula Carótido-Cavernosa/terapia , Fístula Carótido-Cavernosa/etiologia , Tomografia de Coerência Óptica , Embolização Terapêutica/efeitos adversos , Angiografia
15.
Biophys Chem ; 296: 106986, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36905841

RESUMO

Previous studies propose that genetic mutations and post-translational modifications in protein crystallins promote protein aggregation and are considered significant risk factors for cataract formation. The ßB2-crystallin (HßB2C) forms a high proportion of proteins in the human eye lens. Different congenital mutations and post-translational deamidations in ßB2-crystallin have been reported and linked to cataract formation. In this work, we employed extensive all-atom molecular dynamics simulations to evaluate the conformational stability of deamidated and mutated HßB2C. Our results show critical changes in the protein surface and its native contacts due to a modification in the conformational equilibrium of these proteins. The double deamidated (Q70E/Q162E) and single deamidated (Q70E) impact the well compact conformation of the HßB2C. These post-translational modifications allow the exposure of the protein hydrophobic interface, which lead to the exposure of electronegative residues. On the other hand, our mutational studies showed that the S143F mutation modifies the hydrogen-bond network of an antiparallel ß-sheet, unfolding the C-terminal domain. Interestingly, the chain termination mutation (Q155X) does not unfold the N-terminal domain. However, the resultant conformation is more compact and avoids the exposure of the hydrophobic interface. Our results provide valuable information about the first steps of HßB2C unfolding in the presence of deamidated amino acids that have been reported to appear during aging. The findings reported in this work are essential for the general knowledge of the initial steps in the cataract formation mechanism, which may be helpful for the further development of molecules with pharmacological potential against cataract disease.


Assuntos
Catarata , Cristalino , beta-Cristalinas , Humanos , Cristalino/química , Conformação Molecular , Mutação , beta-Cristalinas/metabolismo
16.
Aging Ment Health ; 27(8): 1456-1465, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36218056

RESUMO

Objectives: People with intellectual disability, particularly people with Down syndrome, are at an increased risk for early-onset dementia, in comparison to people without an intellectual disability. The aim of this review was to scope the current landscape of post-diagnostic dementia supports for people with intellectual disability.Method: A systematic search of five electronic databases (CINAHL, Medline, PsycArticles, PsycInfo and Web of Science) was conducted for this scoping review. Results were screened independently by two reviewers, with a third reviewer for arbitration where necessary.Results: Forty-two studies met the inclusion criteria, and relevant information was extracted. The articles included focussed on the experiences of people with intellectual disability and dementia, as well as the role of carers, family members and staff. Key themes included ageing in place, environmental supports for people with intellectual disability and dementia, dementia-specific interventions and therapies, as well as the feasibility of these interventions. Besides the studies that focussed on these themes, other studies focussed on staff training and family supports.Conclusion: This review highlights the importance of implementing timely and appropriate post-diagnostic supports for people living with intellectual disability and dementia. More controlled trials are required on post-diagnostic dementia supports for people with intellectual disability.

17.
ACS Chem Neurosci ; 14(2): 261-269, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36562727

RESUMO

γ-Secretase (GS) is an intramembrane aspartyl protease that participates in the sequential cleavage of C99 to generate different isoforms of the amyloid-ß (Aß) peptides that are associated with the development of Alzheimer's disease. Due to its importance in the proteolytic processing of C99 by GS, we performed pH replica exchange molecular dynamics (pH-REMD) simulations of GS in its apo and substrate-bound forms to sample the protonation states of the catalytic dyad. We found that the catalytic dyad is deprotonated at physiological pH in our apo form, but the presence of the substrate at the active site displaces its monoprotonated state toward physiological pH. Our results show that Asp257 acts as the general base and Asp385 as the general acid during the cleavage mechanism. We identified different amino acids such as Lys265, Arg269, and the PAL motif interacting with the catalytic dyad and promoting changes in its acid-base behavior. Finally, we also found a significant pKa shift of Glu280 related to the internalization of TM6-CT in the GS-apo form. Our study provides critical mechanistic insight into the GS mechanism and the basis for future research on the genesis of Aß peptides and the development of Alzheimer's disease.


Assuntos
Doença de Alzheimer , Secretases da Proteína Precursora do Amiloide , Humanos , Secretases da Proteína Precursora do Amiloide/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/química , Catálise , Simulação de Dinâmica Molecular , Precursor de Proteína beta-Amiloide/metabolismo
18.
J Voice ; 37(6): 957-962, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34452779

RESUMO

PURPOSE: Transgender individuals strive to match their voice and gender identity. An increased glottal gap is often noted on stroboscopy without a clear etiology. We hypothesize this gap can be quantified and results from hormone replacement therapy impacting laryngeal tissues. METHODS: Videostroboscopy exams were retrospectively collected for transgender patients from a tertiary care laryngology practice over two years. Data included hormone duration/type and voice therapy duration. Modal pitch videostroboscopy frame counts determined the open quotient in consecutive vocal fold cycles. Glottal opening was measured using the widest still frame gap during stroboscopy with fully adducted arytenoids. RESULTS: Sixteen transgender patients, along with male and female controls, were included, with 15 patients on hormone therapy (mean = 18 months). Voice therapy, employed in 9/16 patients, ranged from 0 to 23 months (mean = 10.67). One-way ANOVA testing revealed a difference between the open quotient in transgender individuals, males, and females.Tukey's post hoc test identified transgender patients as different from both male (P <0.001) and female (P = 0.037) controls. Length of hormone therapy did not correlate to glottal area measurement or open quotient. Conversely, voice therapy length correlated to increased glottal area (Kendall's Tau = 0.03). Mean phonation time, VHI-10, and mean pitch did not correlate to measured glottal area on stroboscopy. CONCLUSIONS: The increased glottal gap noted in many transgender patients, quantified via the open quotient, differs from male and female controls. Results suggest these findings may correlate to duration of voice therapy.


Assuntos
Pessoas Transgênero , Humanos , Feminino , Masculino , Prega Vocal/diagnóstico por imagem , Estudos Retrospectivos , Identidade de Gênero , Hormônios , Fonação , Estroboscopia
19.
PLoS One ; 17(12): e0275238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36454799

RESUMO

BACKGROUND: Chronic kidney disease (CKD) predispose to viral coinfections in patients submitted to renal replacement therapy (RRT); nevertheless, few reports have been performed to elucidate the current epidemiology within this population in Mexico. AIM: To estimate the prevalence of HBV, HCV, and HIV coinfection and to explore factors associated with prevalent coinfection in patients living with renal failure undergoing to RRT. METHODS: A multicenter cross-sectional recruitment across 21 units at the Mexican Institute of Social Security (IMSS) at the State of Mexico was performed during 2019. A standardized clinical questionnaire was performed to elucidate individual and relatives-related conditions. A treatment facility questionnaire was applied to the chief responsible of each unit to explore treatment facility variables. Serological testing, clinical, biochemical, and anthropometrical parameters were extracted from clinical records. RESULT: In 1,304 patients (57.5% male, mean age 45.5 (SD: 15.6) years, and 95.8% in hemodialysis), the prevalence of any viral coinfection was 3.14% (95% CI: 2.32%-4.23%). The highest viral coinfection prevalence were for HCV, HBV, and HIV, in which men and subjects diagnosed after 2010's had the highest rates. We identify that being submitted to peritoneal dialysis, being treated in a surrogated dialysis center and living with a close relative with prior hepatitis coinfection were associated factors for any viral coinfection. CONCLUSION: In patients submitted to RRT, the prevalence of viral coinfection remains high compared with general population. Screening strategies, medical awareness and targeted public healthcare policies should prioritize better care practices within patients submitted to RRT in Mexico.


Assuntos
Coinfecção , Infecções por HIV , Hepatite B , Hepatite C , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Coinfecção/epidemiologia , Estudos Transversais , México/epidemiologia , Diálise Renal , Hepatite C/complicações , Hepatite C/epidemiologia , Hepacivirus , Hepatite B/complicações , Hepatite B/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Terapia de Substituição Renal , HIV
20.
Vertex ; 33(157): 6-13, 2022 10 10.
Artigo em Espanhol | MEDLINE | ID: mdl-36219192

RESUMO

Objective: To describe the admissions of patients diagnosed with severe mental illness (SMI) and anxiety disorder in a regional hospital; to explore factors related to the patient's referrer upon admission and prolonged stay. Materials and methods: Cross-sectional study of episodes of admission to the regional Psychiatric Hospitalization Unit over a period of 11 years with ICD-10 diagnostic codesF20-29, F30-39, F60-69 and F40-48. The data was extracted through the Admissions Unit and the information from the electronic medical record. For the statistical treatment, descriptive or inferential tests were used with a confidence level of 95%. Results: 961 patients were included (2,324 total discharges), aged 40.8±14.0 years. The most frequent reasons for admission were: positive symptoms (agitation, delusions and hallucinations), followed by suicidal ideation and attempt. The main remitting agent of the patients was the family itself. Approximately 1/5 of the cases were referred by the health system itself, and » of those admitted had self-excluded themselves from specialized supervision for more than a year. Conclusions: The problems that caused the admission and its origin, as well as its lack of follow-up, can be considered as a clear opportunity for improvement in the follow-up of patients with severe mental illness. An orientation towards proactivity, acting before the decompensation, would contribute to improving the care and quality of life of patients with severe mental illness and their environment.


Objetivo: Describir los ingresos de pacientes diagnosticados de enfermedad mental grave y trastorno de ansiedad en un hospital comarcal; explorar los factores relacionados con la derivación del paciente al ingreso y con estancia prolongada. Materiales y métodos: Estudio de corte transversal de los episodios de ingreso en la Unidad de Hospitalización Psiquiátrica comarcal en un periodo de 11 años con los códigos diagnósticos CIE-10 F20-29, F30-39, F60-69 y F40-48. Se extrajeron los datos a través de la Unidad de Admisión y la información de la historia clínica electrónica. Para el tratamiento estadístico se usaron pruebas descriptivas o inferenciales con nivel de confianza del 95%. Resultados: Se incluyeron 961 pacientes (2.324 altas totales), con edad de 40,8±14,0 años. Los motivos más frecuentes de ingreso fueron: síntomas positivos (agitación, delirios y alucinaciones), seguidos de ideación e intento de suicidio. El principal agente remisor de los pacientes fue la propia familia. Aproximadamente 1/5 de casos fue derivado por el propio sistema sanitario, y » de los ingresados se había autoexcluido de la supervisión especializada durante más de un año. Conclusiones: Los problemas causantes del ingreso y su procedencia, así como su falta de seguimiento, pueden considerarse como una oportunidad clara de mejora en el seguimiento del paciente con enfermedad mental grave. Una orientación hacia la proactividad, actuando antes de la descompensación, contribuiría a mejorar la asistencia y calidad de vida de los pacientes con enfermedad mental grave y su entorno.


Assuntos
Hospitalização , Transtornos Mentais , Humanos , Estudos Retrospectivos
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