Energy expenditure estimation during activities of daily living in middle-aged and older adults using an accelerometer integrated into a hearing aid.

Background: Accelerometers were traditionally worn on the hip to estimate energy expenditure (EE) during physical activity but are increasingly replaced by products worn on the wrist to enhance wear compliance, despite potential compromises in EE estimation accuracy. In the older population, where the prevalence of hearing loss is higher, a new, integrated option may arise. Thus, this study aimed to investigate the accuracy and precision of EE estimates using an accelerometer integrated into a hearing aid and compare its performance with sensors simultaneously worn on the wrist and hip. Methods: Sixty middle-aged to older adults (average age 64.0 ± 8.0 years, 48% female) participated. They performed a 20-min resting energy expenditure measurement (after overnight fast) followed by a standardized breakfast and 13 different activities of daily living, 12 of them were individually selected from a set of 35 activities, ranging from sedentary and low intensity to more dynamic and physically demanding activities. Using indirect calorimetry as a reference for the metabolic equivalent of task (MET), we compared the EE estimations made using a hearing aid integrated device (Audéo) against those of a research device worn on the hip (ZurichMove) and consumer devices positioned on the wrist (Garmin and Fitbit). Class-estimated and class-known models were used to evaluate the accuracy and precision of EE estimates via Bland-Altman analyses. Results: The findings reveal a mean bias and 95% limit of agreement for Audéo (class-estimated model) of -0.23 ± 3.33 METs, indicating a slight advantage over wrist-worn consumer devices (Garmin: -0.64 ± 3.53 METs and Fitbit: -0.67 ± 3.40 METs). Class-know models reveal a comparable performance between Audéo (-0.21 ± 2.51 METs) and ZurichMove (-0.13 ± 2.49 METs). Sub-analyses show substantial variability in accuracy for different activities and good accuracy when activities are averaged over a typical day's usage of 10 h (+61 ± 302 kcal). Discussion: This study shows the potential of hearing aid-integrated accelerometers in accurately estimating EE across a wide range of activities in the target demographic, while also highlighting the necessity for ongoing optimization efforts considering precision limitations observed across both consumer and research devices.

Sustained aviremia despite anti-retroviral therapy non-adherence in male children after in utero HIV transmission.

After sporadic reports of post-treatment control of HIV in children who initiated combination anti-retroviral therapy (cART) early, we prospectively studied 284 very-early-cART-treated children from KwaZulu-Natal, South Africa, after vertical HIV transmission to assess control of viremia. Eighty-four percent of the children achieved aviremia on cART, but aviremia persisting to 36 or more months was observed in only 32%. We observed that male infants have lower baseline plasma viral loads (P = 0.01). Unexpectedly, a subset (n = 5) of males maintained aviremia despite unscheduled complete discontinuation of cART lasting 3-10 months (n = 4) or intermittent cART adherence during 17-month loss to follow-up (n = 1). We further observed, in vertically transmitted viruses, a negative correlation between type I interferon (IFN-I) resistance and viral replication capacity (VRC) (P < 0.0001) that was markedly stronger for males than for females (r = -0.51 versus r = -0.07 for IFN-α). Although viruses transmitted to male fetuses were more IFN-I sensitive and of higher VRC than those transmitted to females in the full cohort (P < 0.0001 and P = 0.0003, respectively), the viruses transmitted to the five males maintaining cART-free aviremia had significantly lower replication capacity (P < 0.0001). These data suggest that viremic control can occur in some infants with in utero-acquired HIV infection after early cART initiation and may be associated with innate immune sex differences.

Myeloid cell expression of CD200R is modulated in active TB disease and regulates Mycobacterium tuberculosis infection in a biomimetic model.

A robust immune response is required for resistance to pulmonary tuberculosis (TB), the primary disease caused by Mycobacterium tuberculosis (Mtb). However, pharmaceutical inhibition of T cell immune checkpoint molecules can result in the rapid development of active disease in latently infected individuals, indicating the importance of T cell immune regulation. In this study, we investigated the potential role of CD200R during Mtb infection, a key immune checkpoint for myeloid cells. Expression of CD200R was consistently downregulated on CD14+ monocytes in the blood of subjects with active TB compared to healthy controls, suggesting potential modulation of this important anti-inflammatory pathway. In homogenized TB-diseased lung tissue, CD200R expression was highly variable on monocytes and CD11b+HLA-DR+ macrophages but tended to be lowest in the most diseased lung tissue sections. This observation was confirmed by fluorescent microscopy, which showed the expression of CD200R on CD68+ macrophages surrounding TB lung granuloma and found expression levels tended to be lower in macrophages closest to the granuloma core and inversely correlated with lesion size. Antibody blockade of CD200R in a biomimetic 3D granuloma-like tissue culture system led to significantly increased Mtb growth. In addition, Mtb infection in this system reduced gene expression of CD200R. These findings indicate that regulation of myeloid cells via CD200R is likely to play an important part in the immune response to TB and may represent a potential target for novel therapeutic intervention.

Impact of early antiretroviral therapy, early life immunity and immune sex differences on HIV disease and posttreatment control in children.

PURPOSE OF REVIEW: To review recent insights into the factors affecting HIV disease progression in children living with HIV, contrasting outcomes: following early ART initiation with those in natural, antiretroviral therapy (ART)-naive infection; in children versus adults; and in female individuals versus male individuals. RECENT FINDINGS: Early life immune polarization and several factors associated with mother-to-child transmission of HIV result in an ineffective HIV-specific CD8+ T-cell response and rapid disease progression in most children living with HIV. However, the same factors result in low immune activation and antiviral efficacy mediated mainly through natural killer cell responses in children and are central features of posttreatment control. By contrast, rapid activation of the immune system and generation of a broad HIV-specific CD8+ T-cell response in adults, especially in the context of 'protective' HLA class I molecules, are associated with superior disease outcomes in ART-naive infection but not with posttreatment control. The higher levels of immune activation in female individuals versus male individuals from intrauterine life onwards increase HIV infection susceptibility in females in utero and may favour ART-naive disease outcomes rather than posttreatment control. SUMMARY: Early-life immunity and factors associated with mother-to-child transmission typically result in rapid HIV disease progression in ART-naive infection but favour posttreatment control in children following early ART initiation.

Optimised adaptive procedures and analysis methods for conducting speech-in-noise tests.

OBJECTIVE: Speech-in-noise testing is a valuable part of audiological test batteries. Test standardisation using precise methods is desirable for ease of administration. This study investigated the accuracy and reliability of different Bayesian and non-Bayesian adaptive procedures and analysis methods for conducting speech-in-noise testing. DESIGN: Matrix sentence tests using different numbers of sentences (10, 20, 30 and 50) and target intelligibilities (50 and 75%) were simulated for modelled listeners with various characteristics. The accuracy and reliability of seven different measurement procedures and three different data analysis methods were assessed. RESULTS: The estimation of 50% intelligibility was accurate and showed excellent reliability across the majority of methods tested, even with relatively few stimuli. Estimating 75% intelligibility resulted in decreased accuracy. For this target, more stimuli were required for sufficient accuracy and selected Bayesian procedures surpassed the performance of others. Some Bayesian procedures were also superior in the estimation of psychometric function width. CONCLUSIONS: A single standardised procedure could improve the consistency of the matrix sentence test across a range of target intelligibilities. Candidate adaptive procedures and analysis methods are discussed. These could also be applicable for other speech materials. Further testing with human participants is required.

Single-cell profiling of environmental enteropathy reveals signatures of epithelial remodeling and immune activation.

Environmental enteropathy (EE) is a subclinical condition of the small intestine that is highly prevalent in low- and middle-income countries. It is thought to be a key contributing factor to childhood malnutrition, growth stunting, and diminished oral vaccine responses. Although EE has been shown to be the by-product of a recurrent enteric infection, its full pathophysiology remains unclear. Here, we mapped the cellular and molecular correlates of EE by performing high-throughput, single-cell RNA-sequencing on 33 small intestinal biopsies from 11 adults with EE in Lusaka, Zambia (eight HIV-negative and three HIV-positive), six adults without EE in Boston, United States, and two adults in Durban, South Africa, which we complemented with published data from three additional individuals from the same clinical site. We analyzed previously defined bulk-transcriptomic signatures of reduced villus height and decreased microbial translocation in EE and showed that these signatures may be driven by an increased abundance of surface mucosal cells-a gastric-like subset previously implicated in epithelial repair in the gastrointestinal tract. In addition, we determined cell subsets whose fractional abundances associate with EE severity, small intestinal region, and HIV infection. Furthermore, by comparing duodenal EE samples with those from three control cohorts, we identified dysregulated WNT and MAPK signaling in the EE epithelium and increased proinflammatory cytokine gene expression in a T cell subset highly expressing a transcriptional signature of tissue-resident memory cells in the EE cohort. Together, our work elucidates epithelial and immune correlates of EE and nominates cellular and molecular targets for intervention.

Role of Early Life Cytotoxic T Lymphocyte and Natural Killer Cell Immunity in Paediatric HIV Cure/Remission in the Anti-Retroviral Therapy Era.

Only three well-characterised cases of functional cure have been described in paediatric HIV infection over the past decade. This underlines the fact that early initiation of combination antiretroviral therapy (cART), whilst minimising the size of the viral reservoir, is insufficient to achieve cure, unless other factors contribute. In this review, we consider these additional factors that may facilitate functional cure in paediatric infection. Among the early life immune activity, these include HIV-specific cytotoxic T-lymphocyte (CTL) and natural killer (NK) cell responses. The former have less potent antiviral efficacy in paediatric compared with adult infection, and indeed, in early life, NK responses have greater impact in suppressing viral replication than CTL. This fact may contribute to a greater potential for functional cure to be achieved in paediatric versus adult infection, since post-treatment control in adults is associated less with highly potent CTL activity, and more with effective antiviral NK cell responses. Nonetheless, antiviral CTL responses can play an increasingly effective role through childhood, especially in individuals expressing then 'protective' HLA-I molecules HLA-B*27/57/58:01/8101. The role of the innate system on preventing infection, in shaping the particular viruses transmitted, and influencing outcome is discussed. The susceptibility of female fetuses to in utero mother-to-child transmission, especially in the setting of recent maternal infection, is a curiosity that also provides clues to mechanisms by which cure may be achieved, since initial findings are that viral rebound is less frequent among males who interrupt cART. The potential of broadly neutralising antibody therapy to facilitate cure in children who have received early cART is discussed. Finally, we draw attention to the impact of the changing face of the paediatric HIV epidemic on cure potential. The effect of cART is not limited to preventing AIDS and reducing the risk of transmission. cART also affects which mothers transmit. No longer are mothers who transmit those who carry genes associated with poor immune control of HIV. In the cART era, a high proportion (>70% in our South African study) of transmitting mothers are those who seroconvert in pregnancy or who for social reasons are diagnosed late in pregnancy. As a result, now, genes associated with poor immune control of HIV are not enriched in mothers who transmit HIV to their child. These changes will likely influence the effectiveness of HLA-associated immune responses and therefore cure potential among children.

Irreversible depletion of intestinal CD4+ T cells is associated with T cell activation during chronic HIV infection.

HIV infection in the human gastrointestinal (GI) tract is thought to be central to HIV progression, but knowledge of this interaction is primarily limited to cohorts within Westernized countries. Here, we present a large cohort recruited from high HIV endemic areas in South Africa and found that people living with HIV (PLWH) presented at a younger age for investigation in the GI clinic. We identified severe CD4+ T cell depletion in the GI tract, which was greater in the small intestine than in the large intestine and not correlated with years on antiretroviral treatment (ART) or plasma viremia. HIV-p24 staining showed persistent viral expression, particularly in the colon, despite full suppression of plasma viremia. Quantification of mucosal antiretroviral (ARV) drugs revealed no differences in drug penetration between the duodenum and colon. Plasma markers of gut barrier breakdown and immune activation were elevated irrespective of HIV, but peripheral T cell activation was inversely correlated with loss of gut CD4+ T cells in PLWH alone. T cell activation is a strong predictor of HIV progression and independent of plasma viral load, implying that the irreversible loss of GI CD4+ T cells is a key event in the HIV pathogenesis of PLWH in South Africa, yet the underlying mechanisms remain unknown.

HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells.

SARS-CoV-2 infects epithelial cells of the human gastrointestinal (GI) tract and causes related symptoms. HIV infection impairs gut homeostasis and is associated with an increased risk of COVID-19 fatality. To investigate the potential link between these observations, we analyzed single-cell transcriptional profiles and SARS-CoV-2 entry receptor expression across lymphoid and mucosal human tissue from chronically HIV-infected individuals and uninfected controls. Absorptive gut enterocytes displayed the highest coexpression of SARS-CoV-2 receptors ACE2, TMPRSS2, and TMPRSS4, of which ACE2 expression was associated with canonical interferon response and antiviral genes. Chronic treated HIV infection was associated with a clear antiviral response in gut enterocytes and, unexpectedly, with a substantial reduction of ACE2 and TMPRSS2 target cells. Gut tissue from SARS-CoV-2-infected individuals, however, showed abundant SARS-CoV-2 nucleocapsid protein in both the large and small intestine, including an HIV-coinfected individual. Thus, upregulation of antiviral response genes and downregulation of ACE2 and TMPRSS2 in the GI tract of HIV-infected individuals does not prevent SARS-CoV-2 infection in this compartment. The impact of these HIV-associated intestinal mucosal changes on SARS-CoV-2 infection dynamics, disease severity, and vaccine responses remains unclear and requires further investigation.

Repeatability of sound-evoked triceps myogenic potentials.

OBJECTIVE: To investigate the repeatability of sound-evoked vestibular evoked myogenic potentials recorded from the triceps (tVEMPs) with and without visual feedback. DESIGN: tVEMP responses to 95 dB nHL 500-Hz tone bursts were recorded in a longitudinal, repeated measures study where P1 and N1 latencies and amplitudes were measured on three separate occasions from the same individuals. Analysis of variance, intra-class correlations, and limits of repeatability analyses were used to assess tVEMP repeatability and effects of visual feedback. STUDY SAMPLE: Fifteen participants (nine women) aged between 18 and 41 years took part. RESULTS: Response rates of 63% and 68% were obtained for tVEMPs with eyes open and closed, respectively. When present, tVEMP latencies and amplitudes exhibited fair to good repeatability. Repeatability of tVEMP latencies and amplitudes measured using Bland-Altman methods was poorer with eyes closed. CONCLUSIONS: Sound-evoked tVEMP response rates are too low to support their clinical utility at the moment. tVEMP response rate may be improved by refining the balance task to include a force related target. Better tVEMP repeatability with eyes open supports the hypothesis that the response is modulated by visual feedback, and is consistent with studies reporting triceps responses to galvanic stimulation.

Balance appointment information leaflets: employing performance-based user-testing to improve understanding.

OBJECTIVE: To use performance-based user-testing to evaluate the effectiveness of balance appointment patient information leaflets (PILs) in conveying important information. DESIGN: The study used a sequential groups design. Twenty participants were asked to find and demonstrate understanding of 11 key points of information contained within two NHS leaflets, A and B (10 participants each), through individual structured-interviews. Participants' views of the leaflets were explored through a short semi-structured interview. Following analysis, a revised leaflet was developed and tested on a further 20 participants. STUDY SAMPLE: 40 participants (25F/15M, aged 46-72) with no experience of balance problems or balance assessment appointments. RESULTS: Participants exhibited difficulties with finding and/or understanding 5/11 and 6/11 points of information within leaflets A and B, respectively. Five out of eleven points of the revised leaflet also posed problems. Ten out of eleven points were understood by > 90% of participants testing the revised leaflet compared with 6/11 points for leaflets A and B. CONCLUSIONS: Some balance appointment PILs contain information which is difficult to find and/or understand for some readers. PILs should be evaluated prior to use using performance-based methods, since poor information provision may lead to increased patient anxiety and appointment non-attendance, cancellation, or postponement.

Hearing aid instruction booklets: employing usability testing to determine effectiveness.

PURPOSE: This study implemented performance-based usability and literature testing to determine whether people could use 2 instruction booklets for hearing aids (HAs) to carry out basic maintenance tasks and find and understand key facts. METHOD: Using a cross-sectional study design, researchers recruited 40 participants (25 women, 15 men, ages 46-72 years) with no experience of HAs or audiology services to test instruction booklets for a Danalogic and Unitron HA (20 participants each). Participants were asked to follow instructions provided within the booklets to complete common HA tasks (e.g., cleaning the HA and mold and changing the battery) and demonstrate understanding of information. Participants' views of the booklets were then obtained within a short individual interview. RESULTS: Participants experienced problems in completing all tasks while following instructions provided by the Danalogic and Unitron booklets. Individual interviews highlighted further issues regarding layout, diagrams, and content, including missing information. CONCLUSIONS: Some HA instruction booklets contain information that some users may find difficult to find, understand, and follow. These limitations may negatively impact on HA satisfaction and use. It is recommended that written information for clients be evaluated prior to use. This study supports the premise that performance-based usability and literature testing are appropriate methods to use.

A preliminary investigation into the development of 3-D printing of prosthetic sockets.

The socket is considered an element of major importance in the makeup of a prosthesis. Each socket is a tailor-made device, designed to fit the unique geometry of the patient's residual limb. The design and manufacture of a prosthetic socket traditionally has been a manual process that relies on the use of plaster of Paris casts to capture the shape of the patient's residual limb and then artisan fabrication techniques to manufacture the socket. Computer-aided design and manufacturing technologies have overcome some of the shortcomings of the traditional process, but the final manufacture of the prosthetic socket is still performed manually. Rapid prototyping (RP), a relatively new class of manufacturing technologies, creates physical models directly from three-dimensional (3-D) computer data. Previous research into the application of RP systems to the manufacture of prosthetic sockets has focused on expensive, high-end technologies that have proven too expensive. This paper investigates the use of a cheaper, low-end RP technology known as 3-D printing. Our investigation was an initial approach to using a technology that is normally associated with producing prototypes quickly, some of which could not be manufactured by alternative means. Under normal circumstances, these printed components are weak and relatively fragile. However, comfortable prosthetic sockets manufactured with 3-D printing have been used in preliminary fittings with patients.