Miracle-dz/UniFAR-FTUs huggingface dataset:
Compromised store‐operated Ca2+ entry in aged skeletal muscle

In aged skeletal muscle, changes to the composition and function of the contractile machinery cannot fully explain the observed decrease in the specific force produced by the contractile machinery that characterizes muscle weakness during aging. Since modification in extracellular Ca2+ entry in aged nonexcitable and excitable cells has been recently identified, we evaluated the functional status of store‐operated Ca2+ entry (SOCE) in aged mouse skeletal muscle. Using Mn2+ quenching of Fura‐2 fluorescence and confocal‐microscopic imaging of Ca2+ movement from the transverse tubules, we determined that SOCE was severely compromised in muscle fibers isolated from aged mice (26–27 months) as compared with those from young (2–5 months) mice. While reduced SOCE in aged skeletal muscle does not appear to result from altered expression levels of STIM1 or reduced expression of mRNA for Orai, this reduction in SOCE is mirrored in fibers isolated from young mice null for mitsugumin‐29, a synaptophysin‐related protein that displays decreased expression in aged skeletal muscle. Our data suggest that decreased mitsugumin‐29 expression and reduced SOCE may contribute to the diminished intracellular Ca2+ homeostatic capacity generally associated with muscle aging.
Squamous Cell Carcinoma of the External Auditory Canal and Middle Ear: An Operation Combined with Preoperative Chemoradiotherapy and a Free Surgical Margin

Objective: Treatment outcomes for squamous cell carcinoma of the temporal bone were evaluated regarding stage, therapeutic strategy, and prognostic factors. Study Design: Retrospective case review. Setting: University hospital and outpatient clinic. Patients: Twenty-five patients with primary squamous cell carcinoma of the external auditory canal and middle ear. Intervention: Preoperative chemoradiotherapy and radiotherapy were used in 7 of 12 patients. Lateral temporal bone resection was performed for the lesions not beyond the tympanic membrane. Subtotal temporal bone resection was chosen for lesions extending to the middle ear cavity when there was no invasion to the pyramidal apex, carotid canal, or dura or metastasis. Others were conservatively treated by chemoradiotherapy. When the performance status was poor or an agreement regarding the operation could not be reached, the treatment was modified. Main Outcome Measure: Estimated survival rates. Results: The 3-year estimated survival for T1 and T2 lesions was 100%. The 5-year estimated survival for T3 and T4 lesions was 80% and 35%, respectively. The 5-year estimated survival improved up to 75% for T4 tumors with operation and 16% for those without operation after 47 months. The tumor-free surgical margin is significantly related to patient survival in T3 and T4 lesions. Multivariate analysis predicted that concomitant chronic otitis media and positive lymph nodes were significantly associated with poorer survival. Conclusion: The tumor-free surgical margin was important to survival. When T4 lesions did not involve the pyramidal apex, carotid canal, dura, or any lymph nodes, the surgical intervention improved the estimated survival rate to a level as good as T3 lesions.
Association of recent HIV infection and in-utero HIV-1 transmission

Objective:We previously developed a multiassay algorithm (MAA) to identify recent HIV infection that includes the BED-capture enzyme immunoassay, an avidity assay based on the Genetic Systems HIV-1/HIV-2 + O enzyme immunoassay, CD4 cell count, and HIV viral load. We used this MAA to evaluate the association between recent maternal HIV infection and in-utero transmission of HIV. Methods:Plasma samples were collected at delivery from 2561 HIV-infected women in the postexposure prophylaxis of infants-Malawi trial. The MAA described above was used to identify women with recent HIV infection. Logistic regression models assessed association between recent HIV infection and in-utero HIV transmission (defined as a positive infant HIV DNA test at birth). Results:Seventy-three women were identified as recently infected using the MAA. Those women were younger and had lower parity than women who were identified as not recently infected using the MAA (P < 0.0001 for age and parity). The frequency of in-utero HIV transmission was 17.8% among women identified as recently infected, compared with 6.7% among women identified as not recently infected (13/73 vs. 166/2488, P = 0.001). In a multivariate model, three factors were independently associated with in-utero HIV transmission: recent infection [adjusted odds ratio (AOR): 2.49, 95% confidence interval (CI): 1.30–4.78, P = 0.006], log10 HIV viral load at delivery (AOR: 2.01, 95% CI: 1.60–2.51, P < 0.0001), and younger age (per 10 year increase, AOR: 0.66, 95% CI: 0.43–0.93, P = 0.02). Conclusion:Results obtained using a MAA suggest that recent maternal HIV acquisition is strongly associated with in-utero HIV transmission, independent of HIV viral load at delivery.
Frequency of biocide resistance genes, antibiotic resistance and the effect of chlorhexidine exposure on clinical methicillin-resistant Staphylococcus aureus isolates.

OBJECTIVES To detect genes conferring resistance to biguanides, quaternary ammonium compounds, beta-lactams and fluoroquinolones in clinical methicillin-resistant Staphylococcus aureus (MRSA) and to demonstrate whether reduced susceptibility is spread clonally and if the presence of any of the detected genes links to a specific epidemic MRSA. Finally, to identify if exposure to chlorhexidine may cause reduced susceptibility to antibiotics and chlorhexidine. METHODS In total, 120 clinical MRSA isolates were isolated. qacA/B, qacG, qacH, norA, smr and blaZ genes were amplified by PCR. MICs of eight antibiotics were determined and PFGE was used for typing. Surface disinfection and residue tests were performed for chlorhexidine and a selection of isolates. RESULTS qacA/B (8.3%), qacH (3.3%), norA (36.7%), smr (44.2%) and blaZ (97.5%) were prevalent within the population but qacG was not detected. EMRSA-15 (19.2%), EMRSA-16 (15%), P3 (15%) and H (12.5%) were the most common PFGE types. Clinical isolates demonstrated various degrees of susceptibility to chlorhexidine in the surface disinfection [mean microbiocidal effect (ME) = 0-1.91] and biocide residue (mean ME = 0.29-3.74) tests. Increases in post-exposure MICs were observed in both EMRSA-16 and the susceptible S. aureus control. CONCLUSIONS In our study, isolates resembling PFGE type EMRSA-16 harboured more biocide resistance genes than other types. The observed reduction in susceptibility of clinical isolates to chlorhexidine may mean that a selective pressure is being exerted by residues in the clinical environment, and highlights the importance of efficacy testing on clinical strains and good infection control practices. The development of reduced microbial susceptibility to biocides represents a serious cause for concern in the clinical environment.
Task-Modulated Cortical Representations of Natural Sound Source Categories

In everyday sound environments, we recognize sound sources and events by attending to relevant aspects of an acoustic input. Evidence about the cortical mechanisms involved in extracting relevant category information from natural sounds is, however, limited to speech. Here, we used functional MRI to measure cortical response patterns while human listeners categorized real-world sounds created by objects of different solid materials (glass, metal, wood) manipulated by different sound-producing actions (striking, rattling, dropping). In different sessions, subjects had to identify either material or action categories in the same sound stimuli. The sound-producing action and the material of the sound source could be decoded from multivoxel activity patterns in auditory cortex, including Heschl's gyrus and planum temporale. Importantly, decoding success depended on task relevance and category discriminability. Action categories were more accurately decoded in auditory cortex when subjects identified action information. Conversely, the material of the same sound sources was decoded with higher accuracy in the inferior frontal cortex during material identification. Representational similarity analyses indicated that both early and higher-order auditory cortex selectively enhanced spectrotemporal features relevant to the target category. Together, the results indicate a cortical selection mechanism that favors task-relevant information in the processing of nonvocal sound categories.
Molecular and cellular mechanisms of neuroprotection by vascular endothelial growth factor

The present view of the neuroprotective functions and mechanisms of action of vascular endothelial growth factor (VEGF) is based on studies of neuronal ischemic/hypoxic models in vivo and in vitro. Endogenous neuronal VEGF increases in the ischemic brain and plays a neuroprotective role in the pathophysiologic processes that follow stroke. Exogenous VEGF, directly administered or overexpressed by gene delivery into rat brains, reduces ischemic brain infarct and decreases hypoxic neuronal death. The main neuroprotective mechanisms of VEGF include: (1) modulation of the phosphatidylinositol 3′‐kinase (PI3K)/Akt/nuclear factor‐κB signaling pathway, inhibition of caspase‐3 activity, and reduction of ischemic neuronal apoptosis; (2) inhibition of outward delayed rectifier potassium channel currents and increase of ischemia‐induced tyrosine phosphorylation of Kv1.2 potassium channel proteins via activation of the PI3K pathway; and (3) enhancement of proliferation and migration of neural progenitors in the subventricular zone and improvement of striatal neurogenesis and maturation of newborn neurons in adult rat brains after stroke. © 2004 Wiley‐Liss, Inc.
Frequent Testing of Highly Sexually Active Gay Men is Required to Control Syphilis

Background: The incidence of syphilis infections has been substantially increasing in gay men in the developed world. Methods: We developed an individual-based mathematical model describing syphilis transmission within a gay male population: we used the model to simulate the expected relative impact of numerous screening and treatment interventions, targeting different at-risk groups with various coverage and frequency rates and follow-up schedules. Results: The model predicts that increasing the proportion of gay men tested each year would have a relatively modest impact on syphilis incidence. However, increasing the frequency of testing can have a large impact, with the prevalence of syphilis reduced substantially if individuals are tested every 3 months. Targeting frequent screening at gay men who have large numbers of partners or who engage in group sex is a more efficient way of reducing syphilis epidemics. Contact tracing the regular partners of infected individuals is the most efficient intervention and can have a significant epidemiological impact with relatively high coverage rates. Conclusions: Increasing the frequency of testing and treatment are required to mitigate syphilis epidemics. Notifying and testing partners of infected men should occur where possible but the high rates required to reverse epidemic trends are likely to be infeasible. Contact tracing should be a secondary priority that is coupled with increases in the frequency of testing in the population. Encouraging testing among men not previously tested for syphilis is also recommended.
Effects of Centrally Administered Arginine Vasopressin and Atrial Natriuretic Peptide on the Development of Brain Edema in Hyponatremic Rats

OBJECTIVECentrally released arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) have been shown to participate in brain volume regulation. The aim of the present study was to evaluate the effects of centrally administered AVP and ANP on the time course of development of brain edema in vivo in hyponatremic rats, using diffusion-weighted magnetic resonance imaging. METHODSWe performed intracerebroventricular (ICV) administration of 120 &mgr;g AVP, 20 &mgr;g ANP, or physiological saline into the right lateral ventricle in 18 rats. Twenty-five minutes after the treatment, we induced systemic hyponatremia by the intraperitoneal administration of 140 mmol/L dextrose solution. Serial diffusion-weighted imaging scans were obtained up to 96 minutes after the start of the hyponatremia. Changes in the brain extra- to intracellular volume fraction ratio were estimated as changes in the apparent diffusion coefficient (ADC). RESULTSNo change in the ADC was observed after the ICV injection of saline or AVP. The onset of hyponatremia induced a rapid and marked ADC reduction in both groups, indicating an increased intracellular space. However, the ADC decrease became significantly more pronounced in the ICV AVP group (83.3 ± 4.7% of baseline level, mean ± standard deviation) than in the saline group (93.7 ± 3.3% of baseline, P < 0.001) after 78 minutes of hyponatremia. The ICV injection of ANP induced a prompt ADC increase to 111.5 ± 10.0% (P < 0.05) of the baseline level, indicating a rapid reduction in the intracellular compartment. In the initial phase of hyponatremia, the ADC values in the ANP group were consistently higher than those in the saline group, decreasing finally to 86.9 ± 9.6% after 96 minutes of hyponatremia. CONCLUSIONOur findings demonstrate the opposite effects of AVP and ANP on the intracellular volume fraction of the brain during the development of cellular brain edema, with an immediate effect on ANP and a delayed effect on AVP. The results emphasize the direct effects of these hormones on the cellular volume regulatory mechanisms in the brain during the development of cerebral edema.
The anti-dam protest cycle: evidence from Asia

A major surge in dam construction is under way, and Asia is a hotspot of it. Various policymakers in Asia frame dams as avenues for economic development, yet project-affected communities and civil societies frequently oppose these projects due to their negative environmental and social impacts. While resistance against dam projects in Asia is well documented in the popular press, such environmental activism remains underresearched by scholars. This dissertation addresses this gap. For this purpose, more than 130 semi-structured interviews were carried out via snowball sampling in Myanmar, Thailand, China and Singapore over the course of two years, complemented by online surveying and document analysis. Based on these data, an anti-dam protest cycle is proposed that conceptualizes root causes, strategies and impacts of anti-dam movements in Asia. It also highlights the significant influence of antidam activists on Southeast Asia's dam industry. The cycle commences with the attempt to construct a dam, which can induce significant protests even in countries with limited political opportunity structures, if limited social safeguards in a project coincide with significant environmental risk and rampant corruption. Even if the movement is operating with an extremely limited budget, these protests can cause project suspension and thus continue the cycle — provided that the dam project is framed in a manner that appeals to a broad popular base and/or the movement operates with a sophisticated strategy. Project suspension has been found to have far-reaching effects, with the suspension of Myanmar's Myitsone Dam being identified as a game changer. While Chinese dam developers had previously adopted limited social safeguard norms prior to this dam's suspension, international norms have been increasingly adopted after this incident, since these norms are seen as a pathway to mitigate protests. Yet the negative effects of dams' remaining non-mitigated can continue the anti-dam protest cycle.
Elevated Plasma γ-Tocopherol and Decreased α-Tocopherol in Men Are Associated With Inflammatory Markers and Decreased Plasma 25-OH Vitamin D

Chronic inflammation is a risk factor for many diseases of aging. Endogenous oxidants are thought to mediate the effects of inflammation and γ-Tocopherol (γ-Toc) may mitigate damage from nitrogen-based oxidants; however, no physiological requirement for γ-Toc has been established. Regulation of tocopherols and their functional significance are poorly defined, thereby limiting their application in prevention. Using stored plasma samples from 657 male control subjects in a previous study of prostate cancer, we have analyzed associations of the tocopherols, inflammation markers, and 25-hydroxy (OH) vitamin D. Plasma α-Toc and γ-Toc were inversely correlated, whereas δ-Toc and α-Toc levels were positively correlated, suggesting a unique regulatory mechanism. γ-Toc levels were positively and α-Toc negatively associated with plasma C-reactive protein (CRP) and urinary isoprostane F2t, which are markers of inflammation and oxidation. Ethnic variability in tocopherols was observed; however, this may be explained by differences in plasma 25-OH vitamin D, as γ-Toc levels varied inversely and α-Toc positively with 25-OH vitamin D. In these data, all-cause mortality appeared to be positively associated with CRP and inversely with 25-OH vitamin D. We hypothesize that plasma levels of tocopherols may serve as markers of systemic inflammation, complicating epidemiologic assessment of their role in cancer etiology.
Technical Education in the Middle Income Trap: Building Coalitions for Skill Formation

Abstract This article analyses variations in the provision (breadth and depth) of skill formation through technical and vocational education (TVE) in secondary education in middle-income countries. A growing consensus blames productivity stagnation for the middle-income trap and advocates more human capital to boost productivity. Building on the extensive political economy literature of skill formation in developed economies, the article emphasises the importance of a more demand-side analysis of skill formation. Fragmentation of social groups in middle-income countries discourages the sorts of coalitions that pushed strong public investment in TVE in earlier developers. Brief analyses of exceptional TVE expansion in Chile, Turkey, and Malaysia suggest the importance of a more top-down dynamic led by strong parties and stable governments that compensated for weaker coalitions.
Bioinformatic Analysis of Codon Usage and Phylogenetic Relationships in Different Genotypes of the Hepatitis C Virus

Background The hepatitis C virus (HCV) has six major genotypes. The purpose of this study was to phylogenetically investigate the differences between the genotypes of HCV, and to determine the types of amino acid codon usage in the structure of the virus in order to discover new methods for treatment regimes. Methods The codon usage of the six genotypes of the HCV nucleotide sequence was investigated through the online application available on the website Gene Infinity. Also, phylogenetic analysis and the evolutionary relationship of HCV genotypes were analyzed with MEGA 7 software. Results The six genotypes of HCV were divided into two groups based on their codon usage properties. In the first group, genotypes 1 and 5 (74.02%), and in the second group, genotypes 2 and 6 (72.43%) were shown to have the most similarity in terms of codon usage. Unlike the results with respect to determining the similarity of codon usage, the phylogenetic analysis showed the closest resemblance and correlation between genotypes 1 and 4. The results also showed that HCV has a GC (guanine-cytosine) abundant genome structure and prefers codons with GC for translation. Conclusions Genotypes 1 and 4 demonstrated remarkable similarity in terms of genome sequences and proteins, but surprisingly, in terms of the preferred codons for gene expression, they showed the greatest difference. More studies are therefore needed to confirm the results and select the best approach for treatment of these genotypes based on their codon usage properties.
Peripheral Nerve Injury Alters Blood–Spinal Cord Barrier Functional and Molecular Integrity through a Selective Inflammatory Pathway

Peripheral nerve lesion triggers alterations in the spinal microenvironment that contribute to the pathogenesis of neuropathic pain. While neurons and glia have been implicated in these functional changes, it remains largely underexplored whether the blood–spinal cord barrier (BSCB) is also involved. The BSCB is an important component in the CNS homeostasis, and compromised BSCB has been associated with different pathologies affecting the spinal cord. Here, we demonstrated that a remote injury on the peripheral nerve in rats triggered a leakage of the BSCB, which was independent of spinal microglial activation. The increase of BSCB permeability to different size tracers, such as Evans Blue and sodium fluorescein, was restricted to the lumbar spinal cord and prominent for at least 4 weeks after injury. The spinal inflammatory reaction triggered by nerve injury was a key player in modulating BSCB permeability. We identified MCP-1 as an endogenous trigger for the BSCB leakage. BSCB permeability can also be impaired by circulating IL-1β. In contrast, antiinflammatory cytokines TGF-β1 and IL-10 were able to shut down the openings of the BSCB following nerve injury. Peripheral nerve injury caused a decrease in tight junction and caveolae-associated proteins. Interestingly, ZO-1 and occludin, but not caveolin-1, were rescued by TGF-β1. Furthermore, our data provide direct evidence that disrupted BSCB following nerve injury contributed to the influx of inflammatory mediators and the recruitment of spinal blood borne monocytes/macrophages, which played a major role in the development of neuropathic pain. These findings highlight the importance of inflammation in BSCB integrity and in spinal cord homeostasis.
Comparing self-reported function and work disability in 100 community cases of fibromyalgia syndrome versus controls in London, Ontario: the London Fibromyalgia Epidemiology Study.

OBJECTIVE To compare function and disability in fibromyalgia syndrome (FMS) cases in the community versus controls, and to identify variables predicting poor function and disability. METHODS We identified 100 FMS cases, 76 pain controls, and 135 general controls in a random survey of 3,395 noninstitutionalized adults. RESULTS FMS cases reported worse function (P < 0.00001), more days in bed (P < 0.001), and more healthy years of life lost (P < 0.0001). More FMS cases were disabled (P < 0.00001) and receiving pensions (P < 0.00001). Risk factors for disability included middle age and previous heavy manual labor. Pain, fatigue, and weakness were most often claimed to affect the ability to work Variables predicting work disability were the Fibromyalgia Impact Questionnaire (FIQ) score, a prior diagnosis of FMS, nonrestorative sleep, and past heavy physical labor. Variables influencing the FIQ score were the number of major symptoms, self-reported health satisfaction, tender point count, and education level. CONCLUSION FMS commonly results in loss of function and work disability.