Smell Dysfunction in Patients with Primary Sjögren’s Syndrome: Impact on Quality of Life

Objectives: Patients with primary Sjögren’s syndrome (pSS) often report smell and taste disturbances. However, the correlation between smell impairment and mucosal dryness is not well understood. The objectives of this study were to investigate the following: (1) the prevalence of smell hypofunction in patients with SS; (2) the impact of smell hypofunction on their quality of life (QoL); (3) whether the patients’ smell is correlated with xerostomia; and (4) whether the patients’ smell is affected by taste hypofunction, disease duration, age, smoking or self-reported neuropathy. Methodology: An ethically approved cross-sectional study was conducted on 65 female patients with SS and 62 sex-matched healthy controls. Their smell was assessed using the University of Pennsylvania Smell Identification Test. Their taste acuity was assessed using the Taste Strips Test. A visual analogue scale was used for the self-assessment of smell and taste functions. Xerostomia was assessed by the salivary flow rate, clinical oral dryness score and the Xerostomia Inventory. The patients’ QoL and mental health well-being were assessed using validated questionnaires. Results: In the SS group, the patients’ smell function was impaired in 27/65 patients compared with the controls (15/62, p < 0.05), and it did not correlate with the severity of xerostomia, taste acuity (r = 0.05, p = 0.6) or self-reported nasal dryness (r = −0.02, p = 0.7). In the patients’ group, smell hypofunction was not correlated with disease duration (β = 0.1, 95% CI = −0.07–0.1) or smoking (β = −0.02, 95% CI = −8–7). Age was not correlated with the smell function in the patients’ group (β = −0.1, p = 0.5) but was correlated significantly with smell in the healthy participants’ group (β = −0.3, p = 0.02). Neuropathy affected 81.2% of the patients’ group. Their QoL and mental health well-being were not affected by smell hypofunction. Conclusion: Smell hypofunction appears to be a clinical manifestation in patients with SS, but it does not seem to be associated with the severity of mucosal dryness or with taste disturbance

Difficult management of an extremely rare case of giant pigmented epithelioid melanocytoma

Pigmented epithelioid melanocytoma (PEM), a heavily pigmented and highly uncommon melanocytic lesion, is extremely rare. It comes under several forms and names. We report the case of a three-year-old boy born with an isolated right lumbopelvic and femoral giant PEM. The boy was unable to walk due to the size and the shape of the lesion. He underwent two stages of intra lesional resections, one in Benin and the second in Switzerland. The first surgery was followed by hypothetic hypovolemic and anaphylactic shocks, and the second surgery by a continuous lymphatic leakage from the wounds for months. The strategic management approach, the surgery and follow-up of this case of giant PEM presented a real challenge. (C) 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND licens

Extended magic phase in twisted graphene multilayers

Theoretical and experimental studies have verified the existence of ``magic angles'' in twisted bilayer graphene, where the twist between layers gives rise to flat bands and consequently highly correlated phases. Narrow bands can also exist in multilayers with alternating twist angles, and recent theoretical work suggests that they can also be found in trilayers with twist angles between neighboring layers in the same direction. We show here that flat bands exist in a variety of multilayers where the ratio between twist angles is close to coprime integers. We generalize previous analyses, and, using the chiral limit for interlayer coupling, give examples of many combinations of twist angles in stacks made up of three and four layers which lead to flat bands. The technique we use can be extended to systems with many layers. Our results suggest that flat bands can exist in graphene multilayers with angle disorder, that is, narrow samples of turbostatic graphite.Comment: Main text: 4 pages, 4 figures -- Supplementary Material: 15 pages, 13 figure

Carrier transport theory for twisted bilayer graphene in the metallic regime

The mechanisms responsible for the strongly correlated insulating and superconducting phases in twisted bilayer graphene are still debated. The authors provide a theory for phonon-dominated transport that explains several experimental observations, and contrast it with the Planckian dissipation mechanism. Understanding the normal-metal state transport in twisted bilayer graphene near magic angle is of fundamental importance as it provides insights into the mechanisms responsible for the observed strongly correlated insulating and superconducting phases. Here we provide a rigorous theory for phonon-dominated transport in twisted bilayer graphene describing its unusual signatures in the resistivity (including the variation with electron density, temperature, and twist angle) showing good quantitative agreement with recent experiments. We contrast this with the alternative Planckian dissipation mechanism that we show is incompatible with available experimental data. An accurate treatment of the electron-phonon scattering requires us to go well beyond the usual treatment, including both intraband and interband processes, considering the finite-temperature dynamical screening of the electron-phonon matrix element, and going beyond the linear Dirac dispersion. In addition to explaining the observations in currently available experimental data, we make concrete predictions that can be tested in ongoing experiments

The potential protective effect of metformin on selective cardiac biomarkers in diabetic male rats

Metformin, a biguanide, first line antidiabetic agent, undergoes extensive debate to explain its possible cardioprotective effect. This study represents an attempt to help clarifying this cardioprotective effect. 24rats divided into three diabetic group (8 rats for each) (diabetes induced by Streptozocin 60 mg/kgi.p.). Diabetic groups treated with (saline, 75 mg/kg metformin and 150 mg/kg metformin, i.p.) for 6 weeks, then cardiac stress was induced by isoproterenol (ISO) (150 mg/kg i.p.) for two successive days. Selective biomarkers were assessed; brain natriuretic peptide (BNP), matrix metalloproteinase - 1 (MMP-1) and histopathology examination. The results of this study showed that metformin produce a dose dependent cardioprotection effect in diabetic rats

Marrow adipose tissue expansion coincides with insulin resistance in MAGP1-deficient mice

Marrow adipose tissue (MAT) is an endocrine organ with the potential to influence skeletal remodeling and hematopoiesis. Pathologic MAT expansion has been studied in the context of severe metabolic challenge, including caloric restriction, high fat diet feeding, and leptin deficiency. However, the rapid change in peripheral fat and glucose metabolism associated with these models impedes our ability to examine which metabolic parameters precede or coincide with MAT expansion. Microfibril-associated glycoprotein-1 (MAGP1) is a matricellular protein that influences cellular processes by tethering signaling molecules to extracellular matrix structures. MAGP1-deficient (Mfap2(−/−)) mice display a progressive excess adiposity phenotype, which precedes insulin resistance and occurs without changes in caloric intake or ambulation. Mfap2(−/−) mice were, therefore, used as a model to associate parameters of metabolic disease, bone remodeling, and hematopoiesis with MAT expansion. Marrow adiposity was normal in Mfap2(−/−) mice until 6 months of age; however, by 10 months, marrow fat volume had increased fivefold relative to wild-type control at the same age. Increased gonadal fat pad mass and hyperglycemia were detectable in Mfap2(−/−) mice by 2 months, but peaked by 6 months. The development of insulin resistance coincided with MAT expansion. Longitudinal characterization of bone mass demonstrated a disconnection in MAT volume and bone volume. Specifically, Mfap2(−/−) mice had reduced trabecular bone volume by 2 months, but this phenotype did not progress with age or MAT expansion. Interestingly, MAT expansion in the 10-month-old Mfap2(−/−) mice was associated with modest alterations in basal hematopoiesis, including a shift from granulopoiesis to B lymphopoiesis. Together, these findings indicate MAT expansion is coincident with insulin resistance, but not excess peripheral adiposity or hyperglycemia in Mfap2(−/−) mice; and substantial MAT accumulation does not necessitate a proportional decrease in either bone mass or bone marrow cellularity

The Survival Outcomes of the Metastatic Nonclear Cell Renal Cell Carcinoma in the Immunotherapy Era: Princess Margaret Cancer Centre Experience

Immunotherapy (IO) with or without targeted therapy (TT) is the standard treatment for patients with metastatic clear cell renal cell carcinoma (RCC). The evidence supporting their use in metastatic nonclear cell renal cell carcinoma (nccRCC) subtypes is based on small prospective trials and retrospective analyses. Here, we report survival outcomes for patients with metastatic nccRCC treated with IO and/or TT at the Princess Margaret Cancer Centre, Toronto, ON, Canada. Demographics, disease characteristics, and survival outcomes were collected retrospectively. Overall (OS), progression-free survival (PFS), and objective response rates (ORR) were calculated. We identified 69 patients with metastatic nccRCC treated with IO and/or TT as the first-line treatment, and 36 (52.1%) patients as the second-line treatment. Median OS of the first line IO recipients (n = 12) and non-IO recipients (n = 57) was not reached (NR) and 17.2 months (95% confidence interval (95% CI): 7.3–27.0; P = 0.23), respectively. Median PFS of first-line IO recipients and non-IO recipients was NR and 4.7 months (95% CI: 3.7–5.6; P = 0.019), respectively. The ORR of IO recipients versus non-IO recipients was 50% versus 12.3% (P = 0.007). Median OS of the second-line IO recipients (n = 8) and non-IO recipients (n = 28) was NR and 6.3 months (95% CI: 3.2–9.3; P = 0.003), respectively. Median PFS of second-line IO recipients and non-IO recipients was 4.8 months (95% CI: 2.7–6.8) and 2.8 months (95% CI: 1.8–3.7; P = 0.014), respectively. ORR of IO recipients and non-IO recipients was 37.5% and 3.5%, respectively; P = 0.028. While the number of patients included in our retrospective review was small, our analysis suggested that patients with nccRCC have improved survival outcomes with IO treatment. Validation of prospective dataset is required before widespread clinical utilization

Evaluating the Knowledge, Attitudes, and Practices of Healthcare Workers Regarding High-Risk Nosocomial Infections: A Global Cross-Sectional Study

BACKGROUND: Healthcare workers (HCWs) play a vital role in delivering care and are frequently exposed to the risk of acquiring infections within the hospital setting. Around 15% of hospitalized patients suffer from these infections globally. However, the role and awareness of HCWs in the transmission of hospital-acquired infections (HAIs) or nosocomial infections is still unclear. This study aimed to evaluate the knowledge, attitude, and practices (KAP) toward high-risk microbial infections among HCWs on a global scale to identify measures to address this problem. METHOD: A cross-sectional descriptive study was conducted between 2022 and 2023, with HCWs selected as the study population. Data concerning KAP were collected through a self-administered online survey questionnaire, using a nonprobability convenience sampling method. Descriptive statistics and regression analysis were used to analyze the data. RESULTS: A total of 743 HCWs from various countries participated in the study, with the majority of respondents being doctors (64.9%). Data were mainly obtained from Saudi Arabia (26.78%), Iraq (25.84%), India (15.7%), the United States of America (15.2%), and Africa (Sudan, Nigeria) (13.98%). The frequency of good KAP scores among physicians (KAP: 82.5, 80.66, and 70.5), nurses (KAP: 74.1, 73.07, and 88.7), medical practitioners (KAP: 87.2, 77.58, and 75.1), and technicians (KAP: 76.1, 74.38, and 89.6) were obtained as mentioned. With respect to experience, HCWs showed good KAP scores in 1-5 years (KAP: 82.4, 83.3, and 74.1), 5-10 years (KAP: 80.6, 74.54, 83), 10-20 years (KAP: 74.7, 79.1, and 82.7), and \u3e20 years (KAP: 84.6, 78.8, and 82.8) categories. CONCLUSION: This study suggests that HCWs have good KAP regarding infection prevention, but there is still room for improvement. Educational seminars and awareness programs can provide better adherence to barrier protection measures such as hand washing, use of gloves, and hand disinfection

TURISMO DE ANALFABETOS DIGITAIS EM BALNEÁRIO CAMBORIÚ

O projeto proposto consiste em descobrir como analfabetos digitais podem conhecer pontos turísticos sem utilização de mapas virtuais e como fazem para chegar até eles. Os objetivos específicos do projeto consistem em identificar meios de hospedagem que possuem como público majoritário pessoas da terceira idade, conhecer como é realizada a orientação sobre os atrativos turísticos da cidade para este público-alvo e pesquisar a existência de mapas impressos com os atrativos turísticos e indicação de formas de deslocamentos. Para atingirmos estes objetivos identificamos os hotéis indicados para a terceira idade e selecionamos os 3 principais, então realizamos uma entrevista com o setor de recepção para que eles nos informem como orientam sobre os atrativos turísticos da cidade as pessoas idosas que não acessam a internet. Com isso percebemos que o modo mais rápido de atingir este público-alvo será procurar desenvolver os meios de tornar o turismo inclusivo a todos

Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Recent studies have implicated that chronic hypoxia and insufficient vascular endothelial growth factor (VEGF)-dependent neuroprotection may lead to the degeneration of motor neurons in ALS. Expression of apelin, an endogenous ligand for the G protein-coupled receptor APJ, is regulated by hypoxia. In addition, recent reports suggest that apelin protects neurons against glutamate-induced excitotoxicity. Here, we examined whether apelin is an endogenous neuroprotective factor using SOD1G93A mouse model of ALS. In mouse CNS tissues, the highest expressions of both apelin and APJ mRNAs were detected in spinal cord. APJ immunoreactivity was observed in neuronal cell bodies located in gray matter of spinal cord. Although apelin mRNA expression in the spinal cord of wild-type mice was not changed from 4 to 18 weeks age, that of SOD1G93A mice was reduced along with the paralytic phenotype. In addition, double mutant apelin-deficient and SOD1G93A displayed the disease phenotypes earlier than SOD1G93A littermates. Immunohistochemical observation revealed that the number of motor neurons was decreased and microglia were activated in the spinal cord of the double mutant mice, indicating that apelin deficiency pathologically accelerated the progression of ALS. Furthermore, we showed that apelin enhanced the protective effect of VEGF on H2O2-induced neuronal death in primary neurons. These results suggest that apelin/APJ system in the spinal cord has a neuroprotective effect against the pathogenesis of ALS