Voice self-assessment in individuals with Parkinson's Disease as compared to general voice disorders.

BACKGROUND: Individuals with Parkinson's Disease (IwPD) often fail to adjust their voice in different situations, without awareness of this limitation. Clinicians use self-report questionnaires that are typically designed for individuals with General Voice Disorders (GVD) in the vocal assessment of IwPD. However, these instruments may not consider that IwPD have a reduced self-perception of their vocal deficits. This study aimed to compare self-reported vocal symptoms and voice loudness between IwPD and GVD. METHODS: 28 IwPD and 26 with GVD completed the Voice Symptom Scale (VoiSS) questionnaire to evaluate their voice self-perception. Vocal loudness (dB) was also assessed. Univariate and multivariate analyses were used to compare the outcomes from these measures between the two groups. Principal Component Analysis and Hierarchical Clustering Analysis were applied to explore data patterns related to voice symptoms. RESULTS: IwPD reported significantly fewer vocal symptoms than those with GVD in all VoiSS questionnaire domains. Multivariate principal component analysis found no significant correlations between VoiSS scores and participant similarities in voice measures. Despite experiencing hypophonia, IwPD scored lower in all VoiSS domains but still fell in the healthy voice range. Hierarchical Clustering Analysis grouped participants into three distinct categories, primarily based on age, vocal loudness, and VoiSS domain scores, distinguishing between PD and GVD individuals. CONCLUSIONS: IwPD reported fewer vocal symptoms than GVD. The voice self-assessment seems to be unreliable to assess vocal symptoms in IwPD, at least regarding loudness. New self-report instruments tailored to PD individuals are needed due to their particular voice characteristics.

Clinical Utility and Validation of the Acoustic Voice Quality and Acoustic Breathiness Indexes for Voice Disorder Assessment in English Speakers.

BACKGROUND: While several acoustic voice metrics are available for clinical voice assessment, there remains a significant need for reliable and ecologically valid tools. The Acoustic Voice Quality Index version 03.01 (AVQI-3) and Acoustic Breathiness Index (ABI) hold potential due to their comprehensive assessment approach, incorporating diverse voice aspects. However, these tools still need to be validated in English-speaking populations. METHODS: This study assessed the discriminatory accuracy and validity of AVQI-3 and ABI in 197 participants, including 148 with voice disorders. Voice samples were collected, followed by AVQI-3 and ABI calculations. Additionally, auditory-perceptual assessments were conducted by a panel of speech-language pathologists. RESULTS: AVQI-3 and ABI effectively identified disordered voice quality, evidenced by high accuracy (AUCs: 0.84, 0.89), sensitivity, and specificity (thresholds: AVQI-3 = 1.17, ABI = 2.35). Strong positive correlations were observed with subjective voice quality assessments (rs = 0.72, rs = 0.77, p < 0.001). CONCLUSIONS: The study highlights AVQI-3 and ABI as promising instruments for clinically assessing voice disorders in U.S. English speakers, underscoring their utility in clinical practice and voice research.

Assessment of a diverse panel of transmitted/founder HIV-1 infectious molecular clones in a luciferase based CD8 T-cell mediated viral inhibition assay.

Introduction: Immunological protection against human immunodeficiency virus-1 (HIV-1) infection is likely to require both humoral and cell-mediated immune responses, the latter involving cytotoxic CD8 T-cells. Characterisation of CD8 T-cell mediated direct anti-viral activity would provide understanding of potential correlates of immune protection and identification of critical epitopes associated with HIV-1 control. Methods: The present report describes a functional viral inhibition assay (VIA) to assess CD8 T-cell-mediated inhibition of replication of a large and diverse panel of 45 HIV-1 infectious molecular clones (IMC) engineered with a Renilla reniformis luciferase reporter gene (LucR), referred to as IMC-LucR. HIV-1 IMC replication in CD4 T-cells and CD8 T-cell mediated inhibition was characterised in both ART naive subjects living with HIV-1 covering a broad human leukocyte antigen (HLA) distribution and compared with uninfected subjects. Results & discussion: CD4 and CD8 T-cell lines were established from subjects vaccinated with a candidate HIV-1 vaccine and provided standard positive controls for both assay quality control and facilitating training and technology transfer. The assay was successfully established across 3 clinical research centres in Kenya, Uganda and the United Kingdom and shown to be reproducible. This IMC-LucR VIA enables characterisation of functional CD8 T-cell responses providing a tool for rational T-cell immunogen design of HIV-1 vaccine candidates and evaluation of vaccine-induced T-cell responses in HIV-1 clinical trials.

Cost-effectiveness of couples' voluntary HIV counselling and testing in six African countries: a modelling study guided by an HIV prevention cascade framework.

INTRODUCTION: Couples' voluntary HIV counselling and testing (CVCT) is a high-impact HIV prevention intervention in Rwanda and Zambia. Our objective was to model the cost-per-HIV infection averted by CVCT in six African countries guided by an HIV prevention cascade framework. The HIV prevention cascade as yet to be applied to evaluating CVCT effectiveness or cost-effectiveness. METHODS: We defined a priority population for CVCT in Africa as heterosexual adults in stable couples. Based on our previous experience nationalizing CVCT in Rwanda and scaling-up CVCT in 73 clinics in Zambia, we estimated HIV prevention cascade domains of motivation for use, access and effectiveness of CVCT as model parameters. Costs-per-couple tested were also estimated based on our previous studies. We used these parameters as well as country-specific inputs to model the impact of CVCT over a five-year time horizon in a previously developed and tested deterministic compartmental model. We consider six countries across Africa with varied HIV epidemics (South Africa, Zimbabwe, Kenya, Tanzania, Ivory Coast and Sierra Leone). Outcomes of interest were the proportion of HIV infections averted by CVCT, nationwide CVCT implementation costs and costs-per-HIV infection averted by CVCT. We applied 3%/year discounting to costs and outcomes. Univariate and Monte Carlo multivariate sensitivity analyses were conducted. RESULTS: We estimated that CVCT could avert between 54% (Sierra Leone) and 62% (South Africa) of adult HIV infections. Average costs-per-HIV infection averted were lowest in Zimbabwe ($550) and highest in South Africa ($1272). Nationwide implementations would cost between 7% (Kenya) and 21% (Ivory Coast) of a country's President's Emergency Plan for AIDS Relief (PEPFAR) budget over five years. In sensitivity analyses, model outputs were most sensitive to estimates of cost-per-couple tested; the proportion of adults in heterosexual couples and HIV prevention cascade domains of CVCT motivation and access. CONCLUSIONS: Our model indicates that nationalized CVCT could prevent over half of adult HIV infections for 7% to 21% of the modelled countries' five-year PEPFAR budgets. While other studies have indicated that CVCT motivation is high given locally relevant promotional and educational efforts, without required indicators, targets and dedicated budgets, access remains low.

A Population-Specific Optimized GeneXpert Pooling Algorithm for Chlamydia trachomatis and Neisseria gonorrhoeae To Reduce Cost of Molecular Sexually Transmitted Infection Screening in Resource-Limited Settings.

The sexually transmitted infections (STIs) chlamydia (CT) and gonorrhea (NG) are often asymptomatic in women and undetected by syndromic management, leading to complications such as pelvic inflammatory disease, infertility, and ectopic pregnancy. Molecular testing, such as the GeneXpert CT/NG assay, is highly sensitive, but cost restraints preclude implementation of these technologies in resource-limited settings. Pooled testing is one strategy to reduce the cost per sample, but the extent of savings depends on disease prevalence. The current study describes a pooling strategy based on identification of sociodemographic and laboratory factors associated with CT/NG prevalence in a high-risk cohort of Zambian female sex workers and single mothers conducted from 2016 to 2019. Factors associated with testing positive for CT/NG via logistic regression modeling included city, younger age, lower education, long-acting reversible contraception usage, Trichomonas vaginalis infection, bacterial vaginosis, and incident syphilis infection. Based on these factors, the study population was stratified into high-, intermediate-, and low-prevalence subgroups and tested accordingly-individually, pools of 3, or pools of 4, respectively. The cost per sample was reduced from $18 to as low as $9.43 in the low-prevalence subgroup. The checklist tool and pooling approach described can be used in a variety of treatment algorithms to lower the cost per sample and increase access to molecular STI screening. This is particularly valuable in resource-limited settings to detect and treat asymptomatic CT/NG infections missed by traditional syndromic management.

The Effect of Pulmonary Function on the Incidence of Vocal Fatigue Among Teachers.

INTRODUCTION: Females face a significantly higher risk of presenting with voice problems than males. This discrepancy has been associated with a number of differences in respiratory behavior and the physiology of the laryngeal and endocrine systems. METHODS: In conjunction with established spirometry measures, the Vocal Fatigue Index (VFI) was used to determine (1) if there is a relationship between base pulmonary function and vocal fatigue among teachers; and (2) if that relationship is different in females from males. One hundred and twenty-two elementary and middle school teachers (96 females and 26 males) from the Jordan School District in Northern Utah participated in the study. RESULTS: VFI factors were predictors of the outcomes of several raw spirometry measures for female participants, but the same predictive relationship was not found for male participants. Additionally, there appeared to be no relationship between VFI and spirometry measures in females when using normalized, rather than raw, spirometry metrics. CONCLUSIONS: The results suggest that the pulmonary physiology that would result in reduced raw pulmonary function, in combination with other differences associated with gender, may lead to a greater incidence of vocal fatigue among female teachers than their male counterparts.

HIV testing and counselling couples together for affordable HIV prevention in Africa.

BACKGROUND: The impact and cost-effectiveness of couples' voluntary HIV counselling and testing (CVCT) has not been quantified in real-world settings. We quantify cost-per-HIV-infection averted by CVCT in Zambia from the donor's perspective. METHODS: From 2010 to 2016, CVCT was established in 73 Zambian government clinics. The cost-per-HIV-infection averted (CHIA) of CVCT was calculated using observed expenditures and effectiveness over longitudinal follow-up. These observed measures parameterized hypothetical 5-year nationwide implementations of: 'CVCT'; 'treatment-as-prevention (TasP) for discordant couples' identified by CVCT; and 'population TasP' for all HIV+ cohabiting persons identified by individual testing. RESULTS: In all, 207 428 couples were tested (US $52/couple). Among discordant couples in which HIV+ partners self-reported antiretroviral therapy (ART), HIV incidence was 8.5/100 person-years before and 1.8/100 person-years after CVCT (79% reduction). Corresponding reductions for non-ART-using discordant and concordant negative couples were 63% and 47%, respectively. CVCT averted an estimated 58% of new infections at US $659 CHIA. In nationwide implementation models, CVCT would prevent 17 times the number of infections vs 'TasP for discordant couples' at 86% of the cost, and nine times the infections vs 'population TasP' at 28% of the cost. CONCLUSIONS: CVCT is a cost-effective, feasible prevention strategy in Zambia. We demonstrate the novel, added effectiveness of providing CVCT to ART users, for whom ART use alone only partially mitigated transmission risk. Our results indicate a major policy shift (supporting development of CVCT indicators, budgets and targets) and have clinical implications (suggesting promotion of CVCT in ART clinics as a high-impact prevention strategy).

Characterization and Implementation of a Diverse Simian Immunodeficiency Virus SIVsm Envelope Panel in the Assessment of Neutralizing Antibody Breadth Elicited in Rhesus Macaques by Multimodal Vaccines Expressing the SIVmac239 Envelope.

UNLABELLED: Antibodies that can neutralize diverse viral strains are likely to be an important component of a protective human immunodeficiency virus type 1 (HIV-1) vaccine. To this end, preclinical simian immunodeficiency virus (SIV)-based nonhuman primate immunization regimens have been designed to evaluate and enhance antibody-mediated protection. However, these trials often rely on a limited selection of SIV strains with extreme neutralization phenotypes to assess vaccine-elicited antibody activity. To mirror the viral panels used to assess HIV-1 antibody breadth, we created and characterized a novel panel of 14 genetically and phenotypically diverse SIVsm envelope (Env) glycoproteins. To assess the utility of this panel, we characterized the neutralizing activity elicited by four SIVmac239 envelope-expressing DNA/modified vaccinia virus Ankara vector- and protein-based vaccination regimens that included the immunomodulatory adjuvants granulocyte-macrophage colony-stimulating factor, Toll-like receptor (TLR) ligands, and CD40 ligand. The SIVsm Env panel exhibited a spectrum of neutralization sensitivity to SIV-infected plasma pools and monoclonal antibodies, allowing categorization into three tiers. Pooled sera from 91 rhesus macaques immunized in the four trials consistently neutralized only the highly sensitive tier 1a SIVsm Envs, regardless of the immunization regimen. The inability of vaccine-mediated antibodies to neutralize the moderately resistant tier 1b and tier 2 SIVsm Envs defined here suggests that those antibodies were directed toward epitopes that are not accessible on most SIVsm Envs. To achieve a broader and more effective neutralization profile in preclinical vaccine studies that is relevant to known features of HIV-1 neutralization, more emphasis should be placed on optimizing the Env immunogen, as the neutralization profile achieved by the addition of adjuvants does not appear to supersede the neutralizing antibody profile determined by the immunogen. IMPORTANCE: Many in the HIV/AIDS vaccine field believe that the ability to elicit broadly neutralizing antibodies capable of blocking genetically diverse HIV-1 variants is a critical component of a protective vaccine. Various SIV-based nonhuman primate vaccine studies have investigated ways to improve antibody-mediated protection against a heterologous SIV challenge, including administering adjuvants that might stimulate a greater neutralization breadth. Using a novel SIV neutralization panel and samples from four rhesus macaque vaccine trials designed for cross comparison, we show that different regimens expressing the same SIV envelope immunogen consistently elicit antibodies that neutralize only the very sensitive tier 1a SIV variants. The results argue that the neutralizing antibody profile elicited by a vaccine is primarily determined by the envelope immunogen and is not substantially broadened by including adjuvants, resulting in the conclusion that the envelope immunogen itself should be the primary consideration in efforts to elicit antibodies with greater neutralization breadth.

A gp41-based heteroduplex mobility assay provides rapid and accurate assessment of intrasubtype epidemiological linkage in HIV type 1 heterosexual transmission Pairs.

A critical step in HIV-1 transmission studies is the rapid and accurate identification of epidemiologically linked transmission pairs. To date, this has been accomplished by comparison of polymerase chain reaction (PCR)-amplified nucleotide sequences from potential transmission pairs, which can be cost-prohibitive for use in resource-limited settings. Here we describe a rapid, cost-effective approach to determine transmission linkage based on the heteroduplex mobility assay (HMA), and validate this approach by comparison to nucleotide sequencing. A total of 102 HIV-1-infected Zambian and Rwandan couples, with known linkage, were analyzed by gp41-HMA. A 400-base pair fragment within the envelope gp41 region of the HIV proviral genome was PCR amplified and HMA was applied to both partners' amplicons separately (autologous) and as a mixture (heterologous). If the diversity between gp41 sequences was low (<5%), a homoduplex was observed upon gel electrophoresis and the transmission was characterized as having occurred between partners (linked). If a new heteroduplex formed, within the heterologous migration, the transmission was determined to be unlinked. Initial blind validation of gp-41 HMA demonstrated 90% concordance between HMA and sequencing with 100% concordance in the case of linked transmissions. Following validation, 25 newly infected partners in Kigali and 12 in Lusaka were evaluated prospectively using both HMA and nucleotide sequences. Concordant results were obtained in all but one case (97.3%). The gp41-HMA technique is a reliable and feasible tool to detect linked transmissions in the field. All identified unlinked results should be confirmed by sequence analyses.

Gender differences affecting vocal health of women in vocally demanding careers.

Studies suggest that occupational voice users have a greater incidence of vocal issues than the general population. Women have been found to experience vocal health problems more frequently than men, regardless of their occupation. Traditionally, it has been assumed that differences in the laryngeal system are the cause of this disproportion. Nevertheless, it is valuable to identify other potential gender distinctions which may make women more vulnerable to voice disorders. A search of the literature was conducted for gender-specific characteristics which might impact the vocal health of women. This search can be used by health care practitioners to help female patients avoid serious vocal health injuries, as well as to treat better those women who already suffer from such vocal health issues.