Miracle-dz/UniFAR-FTUs huggingface dataset:
Cognition, brain atrophy, and cerebrospinal fluid biomarkers changes from preclinical to dementia stage of Alzheimer's disease and the influence of apolipoprotein e.

BACKGROUND Knowledge of Alzheimer's disease (AD) manifestation in the pre-dementia stage facilitates the selection of appropriate measures for early detection and disease progression. OBJECTIVE To examine the trajectories of cognitive performance, gray matter volume (GMV), and cerebrospinal fluid (CSF) biomarkers, together with the influence of apolipoprotein E (APOE) in subjects with amyloid-β (Aβ) deposits across the pre-clinical to dementia stages of AD. METHODS 356 subjects were dichotomized into Aβ+ and Aβ- groups based on their CSF Aβ1-42 level. We derived AD-related atrophic regions (AD-ROIs) using the voxel-based morphometry approach. We characterized the trajectories of cognitive scores, GMV at AD-ROIs, and CSF biomarkers from preclinical to disease stages in Aβ+ subjects. The effect of APOE ε4 genotype on these trajectories was examined. RESULTS Impairments in executive functioning/processing speed (EF/PS) and atrophy at the right supramarginal/inferior parietal gyrus were detected in cognitively normal Aβ+ subjects. Together with the APOE ε4 carrier status, these measures showed potential to identify cognitively normal elderly with abnormal CSF Aβ1-42 level in another independent cohort. Subsequently, impairment in memory, visuospatial, language, and attention as well as atrophy in the temporal lobe, thalamus, and mid-cingulate cortex were detectable in Aβ+ mild cognitive impairment (MCI) subjects. In MCI and dementia Aβ+ subjects, ε4 carriers had more severe atrophy of the medial temporal lobe and memory impairment but higher EF/PS compared to non-carriers. CONCLUSIONS EF/PS decline and right parietal atrophy might act as non-invasive screening tests for abnormal amyloid deposition in cognitively normal elderly. APOE modulation on subsequent trajectories in cognition and atrophy should be taken into account when analyzing disease progression.
The mobility experience and neighborhood attachment

In this study, I consider variables associated with an individual’s most recent move into his or her current residence as predictors of neighborhood attachment. Using the 1978–1979 Seattle Community Attachment Survey, I find that elements of the mobility experience such as an individual’s past history of migration, the motivations for moving, the amount of time involved in the move, and the distance traveled during the move have an effect on shortand long-term neighborhood attachment patterns independent of residential stability and investment predictors. The findings imply that psychosocial factors such as familiarity with the environment, increased premove exposure to the new environment, and perceived control during instances of transition have some impact on individuals’ postmove attitudes and behaviors, and suggest that researchers should look beyond traditional “types of people” explanations of urban neighborhood attachment.
New Arsenate Reductase Gene (arrA) PCR Primers for Diversity Assessment and Quantification in Environmental Samples

ABSTRACT The extent of arsenic contamination in drinking water and its potential threat to human health have resulted in considerable research interest in the microbial species responsible for arsenic reduction. The arsenate reductase gene (arrA), an important component of the microbial arsenate reduction system, has been widely used as a biomarker to study arsenate-reducing microorganisms. A new primer pair was designed and evaluated for quantitative PCR (qPCR) and high-throughput sequencing of the arrA gene, because currently available PCR primers are not suitable for these applications. The primers were evaluated in silico and empirically tested for amplification of arrA genes in clones and for amplification and high-throughput sequencing of arrA genes from soil and groundwater samples. In silico, this primer pair matched (≥90% DNA identity) 86% of arrA gene sequences from GenBank. Empirical evaluation showed successful amplification of arrA gene clones of diverse phylogenetic groups, as well as amplification and high-throughput sequencing of independent soil and groundwater samples without preenrichment, suggesting that these primers are highly specific and can amplify a broad diversity of arrA genes. The arrA gene diversity from soil and groundwater samples from the Cache Valley Basin (CVB) in Utah was greater than anticipated. We observed a significant correlation between arrA gene abundance, quantified through qPCR, and reduced arsenic (AsIII) concentrations in the groundwater samples. Furthermore, we demonstrated that these primers can be useful for studying the diversity of arsenate-reducing microbial communities and the ways in which their relative abundance in groundwater may be associated with different groundwater quality parameters. IMPORTANCE Arsenic is a major drinking water contaminant that threatens the health of millions of people worldwide. The extent of arsenic contamination and its potential threat to human health have resulted in considerable interest in the study of microbial species responsible for the reduction of arsenic, i.e., the conversion of AsV to AsIII. In this study, we developed a new primer pair to evaluate the diversity and abundance of arsenate-reducing microorganisms in soil and groundwater samples from the CVB in Utah. We observed significant arrA gene diversity in the CVB soil and groundwater samples, and arrA gene abundance was significantly correlated with the reduced arsenic (AsIII) concentrations in the groundwater samples. We think that these primers are useful for studying the ecology of arsenate-reducing microorganisms in different environments.
Second-Order Perturbative Solution of Cross-Polarized Scattering From Multilayered Rough Surfaces

An analytical solution for the cross-polarized scattering from multilayered media with an arbitrary number of rough interfaces is presented. The second-order perturbative solutions are summations of the Fourier transform pair products of the roughness profiles, and hence, the problem is initially reduced to two generic problems: one with just a single rough surface with two stratified media above and below it and another with two rough interfaces with three stratified media above, between, and below them. The former helps find the second-order contribution of an individual rough interface while the latter is intended to determine the interaction contribution of two arbitrary rough interfaces. In this paper, the second generic problem is solved using the small perturbation method (SPM) based on the extended boundary conditions (EBC). In this SPM formulation, the stratifications are easily accounted for using the generalized coefficients inserted in the dyadic Green's functions (DGFs). Then, the expressions are simplified to find the solution of the first generic problem which is a special case of the second one. Next, the explicit expressions of the generalized coefficients are introduced to the solutions. Subsequently, the interaction terms of the second and the self-term of the first generic problem are combined to find the desired second-order solution. Finally, using the solution derived, a few numerical examples are presented.
Mechanism of Resistance to Several Antimicrobial Agents in Salmonella Clinical Isolates Causing Traveler's Diarrhea

ABSTRACT The evolution of antimicrobial resistance in Salmonella isolates causing traveler's diarrhea (TD) and their mechanisms of resistance to several antimicrobial agents were analyzed. From 1995 to 2002, a total of 62 Salmonella strains were isolated from stools of patients with TD. The antimicrobial susceptibility to 12 antibiotics was determined, and the molecular mechanisms of resistance to several of them were detected as well. The highest levels of resistance were found against tetracycline and ampicillin (21 and 19%, respectively), followed by resistance to nalidixic acid (16%), which was mainly detected from 2000 onward. Molecular mechanisms of resistance were analyzed in 16 isolates. In these isolates, which were resistant to ampicillin, two genes encoding β-lactamases were detected: oxa-1 (one isolate) and tem-like (seven isolates [in one strain concomitantly with a carb-2]). Resistance to tetracycline was mainly related to tetA (five cases) and to tetB and tetG (one case each). Resistance to chloramphenicol was related to the presence of the floR and cmlA genes and to chloramphenicol acetyltransferase activity in one case each. Different genes encoding dihydrofolate-reductases (dfrA1, dfrA12, dfrA14, and dfrA17) were detected in trimethoprim-resistant isolates. Resistance to nalidixic acid was related to the presence of mutations in the amino acid codons 83 or 87 of the gyrA gene. Further surveillance of the Salmonella spp. causing TD is needed to detect trends in their resistance to antimicrobial agents, as we have shown in our study with nalidixic acid. Moreover, such studies will lead to better treatment and strategies to prevent and limit their spread.
Effects of Superpulsed Low-level Laser Therapy on Temporomandibular Joint Pain

ObjectivesA randomized double-blind study was conducted to compare the efficacy of superpulsed low-level laser therapy (SLLLT) with nonsteroidal anti-inflammatory drugs in the treatment of pain caused by temporomandibular joint disorders. MethodsA total of 99 patients with temporomandibular joint disorders, secondary to disc displacement without reduction or osteoarthritis were randomly divided into 3 groups. Thirty-nine patients received SLLLT in 10 sessions over 2 weeks, 30 patients received ibuprofen 800 mg twice a day for 10 days, and 30 patients received sham laser as placebo in 10 sessions over 2 weeks. Pain intensity was measured by visual analog scale at baseline, 2, 5, 10, and 15 days of treatment. Mandibular function was evaluated by monitoring active and passive mouth openings and right and left lateral motions at baseline, 15 days, and 1 month of treatment. Magnetic resonance imaging was performed at baseline and the end of therapy. ResultsMean visual analog scale pain scores in SLLLT group was significantly lower than in nonsteroidal anti-inflammatory drug group and control group (P=0.0001) from fifth day up to the end of the observation period. As for active and passive mouth openings and right and left lateral motions, superiority of SLLLT was evident 1 month after treatment (interaction time treatment, P=0.0001). DiscussionMandibular function improved in all SLLLT patients proving the effectiveness in the treatment of pain, as demonstrated by a significant improvement in clinical signs and symptoms of temporomandibular joint disc displacement without reduction and osteoarthritis at the end of treatment and stability over a period of 1 month.
Molecular Epidemiology of Tuberculosis: Current Insights

SUMMARY Molecular epidemiologic studies of tuberculosis (TB) have focused largely on utilizing molecular techniques to address short- and long-term epidemiologic questions, such as in outbreak investigations and in assessing the global dissemination of strains, respectively. This is done primarily by examining the extent of genetic diversity of clinical strains of Mycobacterium tuberculosis. When molecular methods are used in conjunction with classical epidemiology, their utility for TB control has been realized. For instance, molecular epidemiologic studies have added much-needed accuracy and precision in describing transmission dynamics, and they have facilitated investigation of previously unresolved issues, such as estimates of recent-versus-reactive disease and the extent of exogenous reinfection. In addition, there is mounting evidence to suggest that specific strains of M. tuberculosis belonging to discrete phylogenetic clusters (lineages) may differ in virulence, pathogenesis, and epidemiologic characteristics, all of which may significantly impact TB control and vaccine development strategies. Here, we review the current methods, concepts, and applications of molecular approaches used to better understand the epidemiology of TB.
Subthalamus stimulation in Parkinson disease: Accounting for the bilaterality of contacts

Background: Deep brain stimulation (DBS) in Parkinson's disease uses bi-hemispheric high-frequency stimulation within the subthalamus, however, the specific impacts of bilaterality of DBS are still not clear. Thus, we aimed to study the individual-level clinical impact of locations of right-left contact pair-up accounting for each subthalamic nucleus (STN) anatomy. Methods: Contact locations and effects at 1 year were studied retrospectively in an unselected series of 53 patients operated between 2004 and 2010. Location of contacts was defined relatively to the main axis of STN used to map longitudinal and transversal positions, and STN membership (out meaning out-of-STN). Contact pairings were described via three methods: (i) Unified contact location (UCL) collapsing DBS into an all-in-one contact; (ii) balance of contact pair-up (BCPU), defined as symmetric or asymmetric regardless of laterality; (iii) hemisphere-wise most frequent contact pair-up (MFCP) regardless of BCPU. Clinical data were: mean levodopa equivalent dose, Unified Parkinson's Disease Rating Scale (UPDRS) motor score III without medication, UPDRS II and III speech sub-scores, UPDRS II freezing sub-score, 1 year versus preoperative values, with and without levodopa. Ad-hoc two-sided tests were used for statistical analysis. Results: Worsening speech, was more frequent for UCL_out patients and when the left MFCP contact was rear and/or superolateral, however, it less frequent for BCPU-asymmetric patients. Worsening freezing was more frequent when the right MFCP contact was rear and superolateral. Conclusions: These results point to strategies for minimizing dysarthria and freezing as adverse effects of DBS.
A Two Year Longitudinal Study of Poststroke Mood Disorders: Prognostic Factors Related to One and Two Year Outcome

In a prospective study of mood disorders in 103 stroke patients, we examined the predictive value of affective, cognitive, social and neurologic variables obtained in-hospital and at six months poststroke in terms of outcome as determined by the same measures at one and two years follow-up. The following factors were found to have prognostic significance: 1) Lesion Location: proximity of the lesion on CT scan to the frontal pole in patients with left anterior infarcts showed a strong positive relationship with severity of depression at one year but not at two years poststroke. 2) Affective Status: depression (in-hospital and at 6 months) strongly predicted depression at one year but not at two years poststroke. Additionally, in-hospital depression significantly correlated with physical impairment at two years, while depression at six months bore a moderate relationship to physical impairment at one year. 3) Physical Impairment: impairment in activities of daily living in-hospital bore a modest relationship to depression at one year while such impairment at six months correlated strongly with depression at both one and two years. These findings may reflect the natural course of major depression which remits between one and two years poststroke. Although stroke lesion location is the strongest predictor of subsequent depression, there appears to be a reciprocal relationship between physical impairment and depression (i.e., depression predicts impairment and impairment predicts depression). Since poststroke depressions are amenable to therapeutic intervention, these prognostic factors may have implications for the treatment and rehabilitation of stroke patients.
Optimising the Cutoffs of Cognitive Screening Instruments in Pragmatic Diagnostic Accuracy Studies: Maximising Accuracy or the Youden Index?

Background/Aims: The optimal method of establishing test cutoffs or cutpoints for cognitive screening instruments (CSIs) is uncertain. Of the available methods, two base cutoffs on either the maximal test accuracy or the maximal Youden index. The aim of this study was to compare the effects of using these alternative methods of establishing cutoffs. Methods: Datasets from three pragmatic diagnostic accuracy studies which examined the Mini-Mental State Examination (MMSE), the Addenbrooke's Cognitive Examination-Revised (ACE-R), the Montreal Cognitive Assessment (MoCA), and the Test Your Memory (TYM) test were analysed to calculate test sensitivity and specificity using cutoffs based on either maximal test accuracy or the maximal Youden index. Results: For ACE-R, MoCA, and TYM, optimal cutoffs for dementia diagnosis differed from those in index studies when defined using either the maximal accuracy or the maximal Youden index method. Optimal cutoffs were higher for MMSE, MoCA, and TYM when using the maximal Youden index method and consequently more sensitive. Conclusion: Revision of the cutoffs for CSIs established in index studies may be required to optimise performance in pragmatic diagnostic test accuracy studies which more closely resemble clinical practice.
Do Voice Recordings Reveal whether a Person Is Intoxicated? A Case Study

Abstract In this report we consider the possibility that speech analysis techniques may be used to determine whether an individual was intoxicated at the time that a voice recording was made, and discuss an analysis of the speech produced by the captain of the Exxon Valdez recorded at several points around the time of the accident at Prince William Sound, Alaska. A review of previous research on the effects of alcohol and other effects on speech production suggests that it may be possible to attribute a certain, unique pattern of changes in speech to the influence of alcohol. However, the rate of occurrence of this pattern or the reliability of a decision based on observations such as these is not known. Acoustic-phonetic analysis of a small number of tokens of Captain Hazelwood’s speech recorded before, during and after the accident revealed a number of changes in speech behavior which are similar to the pattern of changes observed in previous laboratory-based research on the effects of alcohol on speech production. We conclude with a discussion of the limitations in making inferences concerning the state of the speaker upon the basis of phonetic data and then discuss several possible explanations of the pattern of change found in the recordings of Captain Hazelwood.
The E3 Ubiquitin Ligase Parkin Is Recruited to the 26 S Proteasome via the Proteasomal Ubiquitin Receptor Rpn13*

Background: The role of the N-terminal ubiquitin-like domain of the E3 ligase parkin is not fully understood. Results: Parkin is recruited to the 26 S proteasome through the interaction of its ubiquitin-like domain with the intrinsic proteasomal ubiquitin receptor Rpn13. Conclusion: Parkin turnover and E3 ligase activity can be regulated by its recruitment to the 26 S proteasome via Rpn13. Significance: Parkin-Rpn13 interaction might be exploited as a potential therapeutic strategy. Mutations in the Park2 gene, encoding the RING-HECT hybrid E3 ubiquitin ligase parkin, are responsible for a common familial form of Parkinson disease. By mono- and polyubiquitinating target proteins, parkin regulates various cellular processes, including degradation of proteins within the 26 S proteasome, a large multimeric degradation machine. In our attempt to further elucidate the function of parkin, we have identified the proteasomal ubiquitin receptor Rpn13/ADRM1 as a parkin-interacting protein. We show that the N-terminal ubiquitin-like (Ubl) domain of parkin binds directly to the pleckstrin-like receptor for ubiquitin (Pru) domain within Rpn13. Using mutational analysis and NMR, we find that Pru binding involves the hydrophobic patch surrounding Ile-44 in the parkin Ubl, a region that is highly conserved between ubiquitin and Ubl domains. However, compared with ubiquitin, the parkin Ubl exhibits greater than 10-fold higher affinity for the Pru domain. Moreover, knockdown of Rpn13 in cells increases parkin levels and abrogates parkin recruitment to the 26 S proteasome, establishing Rpn13 as the major proteasomal receptor for parkin. In contrast, silencing Rpn13 did not impair parkin recruitment to mitochondria or parkin-mediated mitophagy upon carbonyl cyanide m-chlorophenyl hydrazone-induced mitochondrial depolarization. However, it did delay the clearance of mitochondrial proteins (TIM23, TIM44, and TOM20) and enhance parkin autoubiquitination. Taken together, these findings implicate Rpn13 in linking parkin to the 26 S proteasome and regulating the clearance of mitochondrial proteins during mitophagy.
Alcoholic skeletal muscle myopathy: definitions, features, contribution of neuropathy, impact and diagnosis

Alcohol misusers frequently have difficulties in gait, and various muscle symptoms such as cramps, local pain and reduced muscle mass. These symptoms are common in alcoholic patients and have previously been ascribed as neuropathological in origin. However, biochemical lesions and/or the presence of a defined myopathy occur in alcoholics as a direct consequence of alcohol misuse. The myopathy occurs independently of peripheral neuropathy, malnutrition and overt liver disease. Chronic alcoholic myopathy is characterized by selective atrophy of Type II fibres and the entire muscle mass may be reduced by up to 30%. This myopathy is arguably the most prevalent skeletal muscle disorder in the Western Hemisphere and occurs in approximately 50% of alcohol misusers. Alcohol and acetaldehyde are potent inhibitors of muscle protein synthesis, and both contractile and non‐contractile proteins are affected by acute and chronic alcohol dosage. Muscle RNA is also reduced by mechanisms involving increased RNase activities. In general, muscle protease activities are either reduced or unaltered, although markers of muscle membrane damage are increased which may be related to injury by reactive oxygen species. This supposition is supported by the observation that in the UK, α‐tocopherol status is poor in myopathic alcoholics. Reduced α‐tocopherol may pre‐dispose the muscle to metabolic injury. However, experimental α‐tocopherol supplementation is ineffective in preventing ethanol‐induced lesions in muscle as defined by reduced rates of protein synthesis and in Spanish alcoholics with myopathy, there is no evidence of impaired α‐tocopherol status. In conclusion, by a complex series of mechanisms, alcohol adversely affects skeletal muscle. In addition to the mechanical changes to muscle, there are important metabolic consequences, by virtue of the fact that skeletal muscle is 40% of body mass and an important contributor to whole‐body protein turnover.
Treatment of streptomycin-susceptible enterococcal experimental endocarditis with combinations of penicillin and low- or high-dose streptomycin

We used two strains of streptomycin-susceptible enterococci (MIC, 64 and 128 micrograms of streptomycin per ml, respectively) isolated from patients with infective endocarditis. When combined with penicillin, 20 micrograms of streptomycin per ml killed both strains synergistically in vitro whereas combinations of 5 and 10 micrograms of streptomycin per ml did not act synergistically against either strain. By using the rabbit model of enterococcal experimental endocarditis, animals were treated for 3 days with procaine penicillin (1.2 X 10(6) U intramuscularly three times daily) together with low-dose streptomycin (3.5 mg/kg) or high-dose streptomycin (10 mg/kg) intramuscularly three times daily. The peak concentrations of streptomycin in serum at 0.5 h were 9.2 and 26.8 micrograms/ml in the low- or high-dose group, respectively. When combined with procaine penicillin, both dosages of streptomycin were more effective (P less than 0.01) than procaine penicillin alone for the treatment of enterococcal experimental endocarditis. There was no significant difference in the efficacy of procaine penicillin plus low-dose streptomycin versus procaine penicillin plus high-dose streptomycin therapy of enterococcal experimental endocarditis.