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2.
Rev Med Liege ; 76(10): 768-772, 2021 Oct.
Artigo em Francês | MEDLINE | ID: mdl-34632748

RESUMO

Here we present pharmacological and clinical properties of a new fixed triple inhaled combination including an inhaled corticoid, a long acting ?2 agonist and a long acting anticholinergic for the treatment of severe asthma. Enerzair® is the name of this triple combination which contains 160 µg mometasone, 150 µg indacaterol and 50 µg glycopyrronium administered by a Breezhaler®. As compared to an ICS/LABA combination Enerzair® improves expiratory flow rates and reduces exacerbation rate. The Breezhaler® device may be coupled to a sensor (Propeller Health) that, through a bluetooth system, allows to control patient adherence and provides recall to the patient to take his aerosol.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Asma/tratamento farmacológico , Glicopirrolato , Humanos , Indanos , Furoato de Mometasona/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas
3.
Rev Med Liege ; 76(9): 689-696, 2021 Sep.
Artigo em Francês | MEDLINE | ID: mdl-34477341

RESUMO

Since the early 1970s, the concept of quality of life has been the subject of increasing interest in the medical field, although no scientific consensus has emerged on how to define and measure it. The aim of this narrative review of the literature is to decrypt the notion of quality of life in the medical field, in order to enable clinicians-researchers and clinicians who use quality of life measurement instruments in clinical practice to form an informed and nuanced opinion on the issue. To do so, the paper is divided into three parts. Firstly, a brief overview of the origin of the concept in the medical field is given by exposing the main factors explaining its emergence and its rise in importance. Next, the plurality of definitions of quality of life and its derivatives (e.g. health-related quality of life), as well as its measurement instruments in the medical field, are explored. Finally, some benchmarks for the use of health-related quality of life instruments in clinical practice are presented.


Assuntos
Qualidade de Vida , Semântica , Humanos
4.
Artigo em Inglês | MEDLINE | ID: mdl-34280358

RESUMO

PURPOSE: The amount of maximum voluntary clenching (MVC) force may influence functional loading at the polyethylene/metal bearing surfaces in alloplastic total temporomandibular joint replacement (TMJR). The aim of this study was to measure ipsilateral MVC and estimate the risk for revision due to overloading of the TMJR. METHODS: A prospective cohort study design was used to study patients who underwent alloplastic TMJR. The primary predictor was time after TMJR, the secondary predictors were age at TMJR placement, coronoidectomy, prior ipsilateral TMJ surgeries, TMJR design (custom, stock), and bite location. The primary outcome variable was MVC, the secondary outcome was need for TMJR revision. Data were collected preoperatively (T0), and 1 year (T1), 2 to 3 years (T2) and ≥4 years postoperatively (T3). Analysis of variance (ANOVA) with post hoc Tukey-HSD and regression analysis was used for statistical analysis. P < .05 was considered significant. RESULTS: Thirty-seven patients (58 TMJR) with unilateral (n = 16) and bilateral (n = 21) TMJR were enrolled; 8 males (12 TMJR) and 29 females (46 TMJR). Average age was 46.4 ± 14.9 years. MVC increased significantly over the observation period (P = .000). At all observation time points, age at TMJR placement and bite location significantly influenced MVC (P = .000). Coronoidectomy and prior ipsilateral TMJ surgeries did not demonstrate a significant influence on MVC. TMJR design influenced MVC significantly at T3 (P = .006). Regression analysis identified age as a significant factor for higher MVC. No TMJR required revision or replacement. CONCLUSIONS: Based on this study, ipsilateral MVC increases significantly after TMJR. However, since MVC is significantly lower than in healthy test-patients, a considerably lower functional loading at the polyethylene/metal bearing surfaces can be assumed. Lower loading at the TMJR bearing surfaces and at the cortical screw fixation sites suggest a potential longer lifespan compared to other artificial joints like hip and knee prostheses.

5.
J Oral Maxillofac Surg ; 79(10): 2058.e1-2058.e15, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34153254

RESUMO

PURPOSE: Mechanical overloading is a key initiating condition for temporomandibular joint (TMJ) osteoarthritis (OA). The integrin-focal adhesion kinase (FAK) signaling axis is implicated in the mechanobiological response of cells through phosphorylation at Tyr397 (pFAK) but poorly defined in TMJ health and disease. We hypothesize that mechanical overloading disrupts TMJ homeostasis through dysregulation of FAK signaling. MATERIALS AND METHODS: To assess if FAK and pFAK are viable clinical targets for TMJ OA, peri-articular tissues were collected from patients with TMJ OA receiving a total TMJ replacement. To compare clinical samples with preclinical in vivo studies of TMJ OA, the joints of c57/bl6 mice were surgically destabilized and treated with and without inhibitor of pFAK (iFAK). FAK signaling and TMJ OA progression was evaluated and compared using RT-PCR, western blot, immunohistochemistry, and histomorphometry. To evaluate mechanical overloading in vitro, primary murine mandibular fibrochondrocytes were seeded in a 4% agarose-collagen scaffold and loaded in a compression bioreactor with and without iFAK. RESULTS: FAK/pFAK was mostly absent from the articular cartilage layer in the clinical sample and suppressed on the central condyle and elevated on the lateral and medial condyle in murine TMJ OA. In vitro, compressive loading lowered FAK/pFAK levels and elevated the expression of TGFß, NG2, and MMP-13. iFAK treatment suppressed MMP13 and Col6 and elevated TGFß, NG2, and ACAN in a load independent manner. In vivo, iFAK treatment moderately attenuated OA progression and increased collagen maturation. CONCLUSION: These data illustrate that FAK/pFAK is implicated in the signaled dysfunction of excessive mechanical loading during TMJ OA and that iFAK treatment can moderately attenuate the progression of cartilage degeneration in the mandibular condyle.

6.
Langmuir ; 37(27): 8115-8128, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34191521

RESUMO

Marine oil dispersants typically contain blends of surfactants dissolved in solvents. When introduced to the crude oil-seawater interface, dispersants facilitate the breakup of crude oil into droplets that can disperse in the water column. Recently, questions about the environmental persistence and toxicity of commercial dispersants have led to the development of "greener" dispersants consisting solely of food-grade surfactants such as l-α-phosphatidylcholine (lecithin, L) and polyoxyethylenated sorbitan monooleate (Tween 80, T). Individually, neither L nor T is effective at dispersing crude oil, but mixtures of the two (LT blends) work synergistically to ensure effective dispersion. The reasons for this synergy remain unexplained. More broadly, an unresolved challenge is to be able to predict whether a given surfactant (or a blend) can serve as an effective dispersant. Herein, we investigate whether the LT dispersant effectiveness can be correlated with thermodynamic phase behavior in model systems. Specifically, we study ternary "DOW" systems comprising LT dispersant (D) + a model oil (hexadecane, O) + synthetic seawater (W), with the D formulation being systematically varied (across 0:100, 20:80, 40:60, 60:40, 80:20, and 100:0 L:T weight ratios). We find that the most effective LT dispersants (60:40 and 80:20 L:T) induce broad Winsor III microemulsion regions in the DOW phase diagrams (Winsor III implies that the microemulsion coexists with aqueous and oil phases). This correlation is generally consistent with expectations from hydrophilic-lipophilic deviation (HLD) calculations, but specific exceptions are seen. This study then outlines a protocol that allows the phase behavior to be observed on short time scales (ca. hours) and provides a set of guidelines to interpret the results. The complementary use of HLD calculations and the outlined fast protocol are expected to be used as a predictive model for effective dispersant blends, providing a tool to guide the efficient formulation of future marine oil dispersants.


Assuntos
Poluição por Petróleo , Petróleo , Poluentes Químicos da Água , Lecitinas , Poluição por Petróleo/análise , Polissorbatos , Tensoativos , Poluentes Químicos da Água/análise
7.
Braz J Med Biol Res ; 54(8): e10679, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34037091

RESUMO

In spite of the many studies examining alcohol consumption, recent reviews have indicated that binge drinking has not been extensively studied. Furthermore, it is becoming increasingly clear that sleep is associated with many physiological functions and to drug addictions. The present study aimed to evaluate the relationship between alcohol binge drinking and insomnia in college students of health sciences. All first-year health sciences students (n=286) were evaluated in a cross-sectional study. Envelopes containing the Insomnia Severity Index (ISI), the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), and questions capturing sociodemographic data were distributed and collected in classes. It was found that most non-drinkers were female (70.6%), although there were no sex-related differences in the number of binge drinkers (more than 5 drinks on each occasion at least once a week), allowing statistical comparison. The Mann-Whitney U test indicated that the ISI scores were significantly greater in female than male binge drinkers (P=0.014). Moderate or severe insomnia was reported by 23% of the sample, with alcohol being the most frequently associated substance. A specialized intervention was suggested by ASSIST: brief for marijuana (19.2%) and tobacco (23.3%) use, and moderate (31.5%) or intensive (1.4%) for alcohol consumers. The data highlighted the need to pay attention to the habits of college students beyond obtaining scientific information. New data suggesting the influence of genetics on insomnia may be of importance when performing additional studies on the sex differences in alcohol binge drinking.


Assuntos
Consumo Excessivo de Bebidas Alcoólicas , Distúrbios do Início e da Manutenção do Sono , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo Excessivo de Bebidas Alcoólicas/epidemiologia , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Estudantes , Universidades
8.
Arch Microbiol ; 203(5): 2541-2550, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33682076

RESUMO

The spread of multidrug-resistance in Gram-negative bacterial pathogens presents a major clinical challenge, and new approaches are required to combat these organisms. Nitric oxide (NO) is a well-known antimicrobial that is produced by the immune system in response to infection, and numerous studies have demonstrated that NO is a respiratory inhibitor with both bacteriostatic and bactericidal properties. However, given that loss of aerobic respiratory complexes is known to diminish antibiotic efficacy, it was hypothesised that the potent respiratory inhibitor NO would elicit similar effects. Indeed, the current work demonstrates that pre-exposure to NO-releasers elicits a > tenfold increase in IC50 for gentamicin against pathogenic E. coli (i.e. a huge decrease in lethality). It was therefore hypothesised that hyper-sensitivity to NO may have arisen in bacterial pathogens and that this trait could promote the acquisition of antibiotic-resistance mechanisms through enabling cells to persist in the presence of toxic levels of antibiotic. To test this hypothesis, genomics and microbiological approaches were used to screen a collection of E. coli clinical isolates for antibiotic susceptibility and NO tolerance, although the data did not support a correlation between increased carriage of antibiotic resistance genes and NO tolerance. However, the current work has important implications for how antibiotic susceptibility might be measured in future (i.e. ± NO) and underlines the evolutionary advantage for bacterial pathogens to maintain tolerance to toxic levels of NO.


Assuntos
Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Óxido Nítrico/farmacologia , Evolução Biológica , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Gentamicinas/farmacologia , Humanos , Testes de Sensibilidade Microbiana
9.
J Oral Maxillofac Surg ; 79(10): 2016-2029, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33631133

RESUMO

PURPOSE: Unilateral alloplastic total temporomandibular joint reconstruction (TMJR) might influence the contralateral side joint function. This study's purpose was to estimate the risk for contralateral TMJR and the jaw function of the contralateral untreated temporomandibular joint (TMJ). PATIENTS AND METHODS: A prospective cohort study design was used for patients who underwent unilateral alloplastic TMJR. The primary predictor was time after TMJR, and the secondary predictors were pre-TMJR mandibular angle resection, prior ipsilateral TMJ surgeries, and TMJR design (custom, stock). The primary outcome variable was the need for contralateral TMJR. The secondary outcome variables were the results of jaw function-jaw tracking, maximum voluntary clenching, surface electromyography, and pressure pain thresholds (PPT) and patient's quality-of-life (oral health-related quality-of-life [OHrQoL]). Data were collected preoperatively (T0), and 1 year (T1), 2-3 years (T2), and ≥ 4 years postoperatively (T4). Analysis of variance with post hoc Tukey -HSD test and multiple linear regression analysis were used for statistical analysis. P < .05 was considered significant. RESULTS: Thirty-nine patients were enrolled, 15 males and 24 females, with an average age of 48.9 ± 16.2 years. Two patients (5.1%) required a contralateral TMJR. Contralateral condylar motion, incisal laterotrusion, and protrusion slightly decreased, while incisal opening (P = .003), rotation angle (P = .013), opening deflection, surface electromyography activity, maximum voluntary clenching (P = .01), PPTs, and OHrQoL all increased. Pre-TMJR mandibular angle resection had an impact on PPTs and subjective outcomes and prior ipsilateral TMJ surgeries on the opening rotation angle. CONCLUSIONS: Based on this study, bilateral TMJR does not appear necessary when the contralateral TMJ is healthy. Unilateral alloplastic TMJR is associated with improved contralateral jaw function and OHrQoL.

10.
J Oral Maxillofac Surg ; 79(7): 1423-1433, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33549540

RESUMO

PURPOSE: To survey temporomandibular joint (TMJ) surgeons to determine current practice trends and perceptions regarding the role of discectomy for the treatment of TMJ internal derangements. METHODS: An anonymous 5-part web-based survey was sent to TMJ surgeons. The survey was created and distributed, and the data were collected with the University of Michigan Qualtrics platform. Responses were compared based on operative volume, tendency to replace the disc, and likelihood of requiring temporomandibular joint replacement (TJR) after discectomy. Spearman correlations were used to test statistically significant differences. Domain-level analyses were also performed by summarizing items into 3 domain scores. Analyses were performed in SAS V9.4 (SAS Institute Inc., Cary, NC, USA). RESULTS: Fifty-nine surgeons (33.9%) completed the survey. Discectomy was not considered to be a useful procedure by 85% of respondents, and 74% would not consider discectomy as a first surgical option. Most would consider discectomy (64%) before alloplastic total joint replacement. Discectomy was preferred over discopexy for the management of anterior disc displacement with reduction by high volume surgeons (89%), but most (72%) did not feel that discectomy was beneficial over arthroscopy in the treatment of anterior disc displacement without reduction and concomitant degenerative bony changes. In managing symptomatic disc perforation, 66% agreed that discectomy is the procedure of choice and 49% felt that interpositional tissue is indicated in most cases after discectomy. Respondents who reported fewer re-operations requiring alloplastic TJR after discectomy had, on average, more positive perceptions of discectomy on the benefits domain (P = .03), better than alternatives domain (P = .03), and fewer concerns on the perceived adverse effects domain (P = .03). CONCLUSIONS: TMJ surgeons do not employ TMJ discectomy in most cases of TMJ internal derangement. However, discectomy is considered useful in cases of disc perforation or for persistent symptomatic disc displacement without reduction, in an attempt to avoid alloplastic TJR. Common adverse effects included joint noises and osteoarthrosis, and the use of interpositional disc replacement tissue did not alter the incidence of adverse effects or complications reported.


Assuntos
Luxações Articulares , Cirurgiões , Transtornos da Articulação Temporomandibular , Discotomia , Humanos , Luxações Articulares/cirurgia , Inquéritos e Questionários , Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/cirurgia
11.
Org Lett ; 23(4): 1500-1503, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33533625

RESUMO

Oxazoles are rapidly assembled through a sequential deprotonation-condensation of Asmic, anisylsulfanylmethylisocyanide, with esters followed by sulfanyl-lithium exchange-trapping. Deprotonating Asmic affords a metalated isocyanide that efficiently traps esters to afford oxazoles bearing a versatile C-4 anisylsulfanyl substituent. Interchange of the anisylsulfanyl substituent is readily achieved through a first-in-class sulfur-lithium exchange-electrophilic trapping sequence whose versatility is illustrated in the three-step synthesis of the bioactive natural product streptochlorin.

12.
Cell Mol Gastroenterol Hepatol ; 11(1): 99-115, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32735995

RESUMO

BACKGROUND & AIMS: Chronic amino acid (AA) deficiency, as in kwashiorkor, reduces the size of the pancreas through an effect on mammalian target of rapamycin complex 1 (mTORC1). Because of the physiological importance of AAs and their role as a substrate, a stimulant of mTORC1, and protein synthesis, we studied the effect of acute protein and AA deficiency on the response to feeding. METHODS: ICR/CD-1 mice were fasted overnight and refed for 2 hours with 4 different isocaloric diets: control (20% Prot); Protein-free (0% Prot); control (AA-based diet), and a leucine-free (No Leu). Protein synthesis, polysomal profiling, and the activation of several protein translation factors were analyzed in pancreas samples. RESULTS: All diets stimulated the Protein Kinase-B (Akt)/mTORC1 pathway, increasing the phosphorylation of the kinase Akt, the ribosomal protein S6 (S6) and the formation of the eukaryotic initiation factor 4F (eIF4F) complex. Total protein synthesis and polysome formation were inhibited in the 0% Prot and No Leu groups to a similar extent, compared with the 20% Prot group. The 0% Prot diet partially reduced the Akt/mTORC1 pathway and the activity of the guanine nucleotide exchange factor eIF2B, without affecting eIF2α phosphorylation. The No Leu diet increased the phosphorylation of eIF2α and general control nonderepressible 2, and also inhibited eIF2B activity, without affecting mTORC1. Essential and nonessential AA levels in plasma and pancreas indicated a complex regulation of their cellular transport mechanisms and their specific effect on the synthesis of digestive enzymes. CONCLUSIONS: These studies show that dietary AAs are important regulators of postprandial digestive enzyme synthesis, and their deficiency could induce pancreatic insufficiency and malnutrition.

13.
Psychother Res ; 31(1): 63-77, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32406339

RESUMO

Objective: There is a paucity of studies examining the experience of clients who undergo multiple courses of psychotherapy. Conducted within a large practice research network, this study demonstrated that returning therapy clients comprise a considerable portion of the clinical population in university counseling settings, and identified variables associated with return to therapy. Method: Utilizing data spanning 2013 to 2017, statistical variable selection for predicting return to therapy was conducted via grouped least absolute shrinkage and selection operator (grouped LASSO) applied to logistic regression. The grouped LASSO approach is described in detail to facilitate learning and replication. The paper also addresses methodological considerations related to this approach, such as sample size, generalizability, as well as general strengths and limitations. Results: Attendance rate, duration of initial treatment course, social anxiety, perceived social support, academic distress, and alcohol use were identified as predictive of return to therapy. Conclusions: Findings could help inform more cost-effective policies for session limits (e.g., extending session limits for clients with social anxiety), referral decisions (e.g., for clients with alcohol use problems), and appointment reminders (based on the association between poor attendance rate and return to therapy). Taking into account the many reasons that can explain why clients do or do not return to therapy, these findings also could inform clinicians' early case conceptualizations and treatment interventions.


Assuntos
Aconselhamento , Psicoterapia , Humanos , Apoio Social
14.
J Oral Maxillofac Surg ; 79(2): 314-323, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33053373

RESUMO

PURPOSE: Total alloplastic temporomandibular joint replacement (TMJR) requires the detachment of the masseter muscle (MM) at its insertion to the lateral ramus and often the resection of the coronoid process (insertion of the temporalis muscle). There is little literature on how a detachment affects the muscles. The present study evaluates the long-term masticatory muscle activities and maximum voluntary bite force (MVC) in patients with unilateral TMJR. PATIENTS AND METHODS: Surface electromyography of the MM and anterior temporalis muscle during bite force testing and MVC were evaluated bilateral preoperatively (T0), 1 (T3), 2 (T4), 3 (T5), and 4 years (T6) postoperatively. The percentage overlapping coefficient (index of the symmetric distribution of muscular activity) was calculated. Differences between stock or custom devices were evaluated. RESULTS: Fourteen patients were enrolled, 4 males and 10 females, age 47.3 ± 14.3 years at TMJR placement. In 11 patients, the coronoid process was resected, 5 patients received stock, and 9 custom prostheses. After surgery, a trend in the improvement of bilateral surface electromyography activities and MVC was found without statistical significance for the side comparison or the time of the investigation. The percentage overlapping coefficient values showed postoperatively relative (>72%) symmetry in both muscles. Up to T5 on the TMJR side, MM showed higher activity when custom prostheses were used. There was no significant difference between stock and custom prostheses. CONCLUSIONS: The vertical (anterior) fibers of the temporalis muscle are preserved despite the resection of the coronoid process. The anterior temporalis muscle, as a synergist of the MM on the TMJR side, postoperatively partially assumes its abduction function. The detached MM appears to reattach. Generally, the bilateral increase in muscle activity and MVC of both muscles suggests regeneration of the investigated muscles. Custom prostheses seem to have an initial advantage for the reattachment of the MM compared with stock prostheses.


Assuntos
Músculo Masseter , Músculo Temporal , Adulto , Força de Mordida , Eletromiografia , Feminino , Humanos , Masculino , Músculo Masseter/cirurgia , Pessoa de Meia-Idade , Contração Muscular , Estudos Prospectivos , Músculo Temporal/cirurgia , Articulação Temporomandibular/cirurgia
15.
Braz. j. med. biol. res ; 54(8): e10679, 2021. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1249325

RESUMO

In spite of the many studies examining alcohol consumption, recent reviews have indicated that binge drinking has not been extensively studied. Furthermore, it is becoming increasingly clear that sleep is associated with many physiological functions and to drug addictions. The present study aimed to evaluate the relationship between alcohol binge drinking and insomnia in college students of health sciences. All first-year health sciences students (n=286) were evaluated in a cross-sectional study. Envelopes containing the Insomnia Severity Index (ISI), the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), and questions capturing sociodemographic data were distributed and collected in classes. It was found that most non-drinkers were female (70.6%), although there were no sex-related differences in the number of binge drinkers (more than 5 drinks on each occasion at least once a week), allowing statistical comparison. The Mann-Whitney U test indicated that the ISI scores were significantly greater in female than male binge drinkers (P=0.014). Moderate or severe insomnia was reported by 23% of the sample, with alcohol being the most frequently associated substance. A specialized intervention was suggested by ASSIST: brief for marijuana (19.2%) and tobacco (23.3%) use, and moderate (31.5%) or intensive (1.4%) for alcohol consumers. The data highlighted the need to pay attention to the habits of college students beyond obtaining scientific information. New data suggesting the influence of genetics on insomnia may be of importance when performing additional studies on the sex differences in alcohol binge drinking.

16.
Jamba ; 12(1): 947, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240466

RESUMO

Informal backyard rentals (IBRs) constitute South Africa's fastest growing housing subsector, flourishing within a relative research vacuum and without national policy intervention to address the vulnerabilities of stakeholders to the health risks potentially presented. This article reviewed the literature on IBRs, focussing on past policies and interventions, general characteristics, infrastructure and service access to inform an analysis of potential health risks from the existing literature to guide future research and policy-making. Research followed a qualitative approach to review IBR literature dating after 2004. Relevant publications were identified from bibliographic databases using Boolean search logic and by reviewing citations in and later citations of these publications. Relevant secondary sources were also included. The review evidenced that IBRs have received increasing policy, but limited research attention, and that health hazards have been particularly neglected. Although issues such as shared water and sanitation, inappropriate waste disposal, poor hygiene practices, high densities and poor quality structures have been referenced extensively - alluding to risks and health concerns - few studies have focussed directly on health, risk and vulnerability. The risk analysis completed based on the literature made potential risks explicit, exemplified by references to specific conditions, such as HIV/AIDS, tuberculosis and the coronavirus pandemic, demonstrating pathogenic pathways, contamination and transmission risks conducive to poor health, infection and potential disaster. The review captured and updated the contemporary literature on IBRs, with the subsequent analysis providing a platform for future empirical research on health, infrastructure and IBRs to address potential risks towards positive change in future policies.

17.
J Neurosci ; 40(46): 8816-8830, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33051347

RESUMO

The neurokinin-1 receptor (NK1R; encoded by Tacr1) is expressed in spinal dorsal horn neurons and has been suggested to mediate itch in rodents. However, previous studies relied heavily on neurotoxic ablation of NK1R spinal neurons, which limited further dissection of their function in spinal itch circuitry. To address this limitation, we leveraged a newly developed Tacr1CreER mouse line to characterize the role of NK1R spinal neurons in itch. We show that pharmacological activation of spinal NK1R and chemogenetic activation of Tacr1CreER spinal neurons increases itch behavior in male and female mice, whereas pharmacological inhibition of spinal NK1R suppresses itch behavior. We use fluorescence in situ hybridization (FISH) to characterize the endogenous expression of Tacr1 throughout the superficial and deeper dorsal horn (DDH), as well as the lateral spinal nucleus (LSN), of mouse and human spinal cord. Retrograde labeling studies in mice from the parabrachial nucleus (PBN) show that less than 20% of superficial Tacr1CreER dorsal horn neurons are spinal projection neurons, and thus the majority of Tacr1CreER are local interneurons. We then use a combination of in situ hybridization and ex vivo two-photon Ca2+ imaging of the mouse spinal cord to establish that NK1R and the gastrin-releasing peptide receptor (GRPR) are coexpressed within a subpopulation of excitatory superficial dorsal horn (SDH) neurons. These findings are the first to suggest a role for NK1R interneurons in itch and extend our understanding of the complexities of spinal itch circuitry.SIGNIFICANCE STATEMENT The spinal cord is a critical hub for processing somatosensory input, yet which spinal neurons process itch input and how itch signals are encoded within the spinal cord is not fully understood. We demonstrate neurokinin-1 receptor (NK1R) spinal neurons mediate itch behavior in mice and that the majority of NK1R spinal neurons are local interneurons. These NK1R neurons comprise a subset of gastrin-releasing peptide receptor (GRPR) interneurons and are thus positioned at the center of spinal itch transmission. We show NK1R mRNA expression in human spinal cord, underscoring the translational relevance of our findings in mice. This work is the first to suggest a role for NK1R interneurons in itch and extends our understanding of the complexities of spinal itch circuitry.


Assuntos
Interneurônios , Rede Nervosa/fisiopatologia , Prurido/fisiopatologia , Receptores da Bombesina/biossíntese , Receptores da Bombesina/genética , Receptores da Neurocinina-1/biossíntese , Receptores da Neurocinina-1/genética , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Adulto , Animais , Comportamento Animal , Plexo Braquial/fisiopatologia , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Dor/psicologia , Células do Corno Posterior/metabolismo , Prurido/genética , Prurido/psicologia
18.
Am J Physiol Heart Circ Physiol ; 319(3): H582-H603, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32762558

RESUMO

Duchenne muscular dystrophy (DMD) is an X-linked disease caused by null mutations in dystrophin and characterized by muscle degeneration. Cardiomyopathy is common and often prevalent at similar frequency in female DMD carriers irrespective of whether they manifest skeletal muscle disease. Impaired muscle nitric oxide (NO) production in DMD disrupts muscle blood flow regulation and exaggerates postexercise fatigue. We show that circulating levels of endogenous methylated arginines including asymmetric dimethylarginine (ADMA), which act as NO synthase inhibitors, are elevated by acute necrotic muscle damage and in chronically necrotic dystrophin-deficient mice. We therefore hypothesized that excessive ADMA impairs muscle NO production and diminishes exercise tolerance in DMD. We used transgenic expression of dimethylarginine dimethylaminohydrolase 1 (DDAH), which degrades methylated arginines, to investigate their contribution to exercise-induced fatigue in DMD. Although infusion of exogenous ADMA was sufficient to impair exercise performance in wild-type mice, transgenic DDAH expression did not rescue exercise-induced fatigue in dystrophin-deficient male mdx mice. Surprisingly, DDAH transgene expression did attenuate exercise-induced fatigue in dystrophin-heterozygous female mdx carrier mice. Improved exercise tolerance was associated with reduced heart weight and improved cardiac ß-adrenergic responsiveness in DDAH-transgenic mdx carriers. We conclude that DDAH overexpression increases exercise tolerance in female DMD carriers, possibly by limiting cardiac pathology and preserving the heart's responses to changes in physiological demand. Methylated arginine metabolism may be a new target to improve exercise tolerance and cardiac function in DMD carriers or act as an adjuvant to promote NO signaling alongside therapies that partially restore dystrophin expression in patients with DMD.NEW & NOTEWORTHY Duchenne muscular dystrophy (DMD) carriers are at risk for cardiomyopathy. The nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is released from damaged muscle in DMD and impairs exercise performance. Transgenic expression of dimethylarginine dimethylaminohydrolase to degrade ADMA prevents cardiac hypertrophy, improves cardiac function, and improves exercise tolerance in DMD carrier mice. These findings highlight the relevance of ADMA to muscular dystrophy and have important implications for therapies targeting nitric oxide in patients with DMD and DMD carriers.


Assuntos
Arginina/análogos & derivados , Cardiomiopatias/metabolismo , Circulação Coronária , Tolerância ao Exercício , Heterozigoto , Distrofia Muscular de Duchenne/metabolismo , Miocárdio/metabolismo , Músculo Quadríceps/metabolismo , Amidoidrolases/genética , Amidoidrolases/metabolismo , Animais , Arginina/metabolismo , Cardiomiopatias/genética , Cardiomiopatias/fisiopatologia , Modelos Animais de Doenças , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Camundongos Transgênicos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/fisiopatologia , Miocárdio/patologia , Necrose , Músculo Quadríceps/patologia , Músculo Quadríceps/fisiopatologia , Função Ventricular Esquerda
19.
J Oral Maxillofac Surg ; 78(10): 1692-1703, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32610046

RESUMO

PURPOSE: The purpose of the present study was to report the temporomandibular joint (TMJ) alloplastic reconstruction (TMJR) revision and/or replacement rates and associated complication outcomes data gathered from experienced TMJ surgeons and to review the recent relevant data. MATERIALS AND METHODS: A 21-question anonymous on-line survey was sent to all Commission on Dental Accreditation-approved oral and maxillofacial surgery program directors and to members of the European Society of TMJ Surgeons and the American Society of Temporomandibular Joint Surgeons. RESULTS: Of the surgeons sent the survey, 22% completed the full questionnaire. Most responses were from surgeons who routinely perform TMJR surgery (93.5%). Of the respondents, 28.3% had more than 30 years of experience and 73.9% were full-time academic faculty. A total of 4638 TMJR procedures were recorded and analyzed. The incidence of TMJR revision (keeping the same device) was 3% and that of replacement (placing a new device) was 4.9%. The most common reason for revision was heterotopic ossification (27.5%). The most common reason for replacement was infection (21.1%). Revision was successful in 86.7% and replacement in 94.6% of the patients at the longest follow-up reported. CONCLUSIONS: The data from the present study have shown that the incidence is low and the success rate is high for TMJR revision and replacement.


Assuntos
Artroplastia de Substituição , Prótese Articular , Transtornos da Articulação Temporomandibular , Humanos , Inquéritos e Questionários , Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/cirurgia
20.
J Consult Clin Psychol ; 88(10): 907-922, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32584115

RESUMO

Objective: Although most self-report measures of distress are intended to assess time-varying constructs, they are usually developed using between-person data. They are therefore vulnerable to misspecification due to measurement nonequivalence at the between-person and within-person levels. In recent years, multiple studies have found that self-report distress may not be the same when considered over time versus between people: what changes over time may not be the same as what makes individuals different from one another. Method: In this study, we present a multilevel factor analysis (MFA) of a widely used multidimensional self-report measure of psychological symptoms, the Counseling Center Assessment of Psychological Symptoms-34 (CCAPS-34), in two samples (Ns: 1,223 and 757) of individuals with 10 or more observations each. We compare the results to traditional factor analysis. Results: Single-level factor analyses converged with the established seven-factor structure, regardless of sample or data subset. The MFA largely, but not entirely, recovered the existing factor structure of the CCAPS-34 at the within-person level in both samples, but not at the between-person level. The between-person factor structure was simpler than the within-person factor structure, particularly in the nonclinical sample in which only two factors were sufficient. Conclusions: The factors of this instrument that change over time appear to be narrow, while differences between people are broader. This argues against using general distress measures when assessing treatment outcomes. MFA is a promising method for measure development, even in data with relatively few observations per person. This method may clarify how self-report psychopathology manifests over time. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Análise Fatorial , Transtornos Mentais/diagnóstico , Adolescente , Adulto , Feminino , Humanos , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Análise Multinível , Testes Psicológicos , Projetos de Pesquisa , Autorrelato , Adulto Jovem
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