Tubulin isoform composition tunes microtubule dynamics

Microtubules polymerize and depolymerize stochastically, a behavior essential for cell division, motility and differentiation. While many studies advanced our understanding of how microtubule-associated proteins tune microtubule dynamics in trans, we have yet to understand how tubulin genetic diversity regulates microtubule functions. The majority of in vitro dynamics studies are performed with tubulin purified from brain tissue. This preparation is not representative of tubulin found in many cell types. Here we report the 4.2Å cryo-EM structure and in vitro dynamics parameters of α1B/βI+βIVb microtubules assembled from tubulin purified from a human embryonic kidney cell line with isoform composition characteristic of fibroblasts and many immortalized cell lines. We find that these microtubules grow faster and transition to depolymerization less frequently compared to brain microtubules. Cryo-EM reveals that the dynamic ends of α1B/βI+βIVb microtubules are less tapered and that these tubulin heterodimers display lower curvatures. Interestingly, analysis of EB1 distributions at dynamic ends suggests no differences in GTP cap sizes. Lastly, we show that the addition of recombinant α1A/βIII tubulin, a neuronal isotype overexpressed in many tumors, proportionally tunes the dynamics of α1B/βI+βIVb microtubules. Our study is an important step towards understanding how tubulin isoform composition tunes microtubule dynamics

Is the HIV burden in India being overestimated?

BACKGROUND: The HIV burden estimate for India has a very wide plausibility range. A recent population-based study in a south Indian district demonstrated that the official method used in India to estimate HIV burden in the population, which directly extrapolates annual sentinel surveillance data from large public sector antenatal and sexually transmitted infection (STI) clinics, led to a 2–3 times higher estimate than that based on population-based data. METHODS: We assessed the generalisability of the reasons found in the Guntur study for overestimation of HIV by the official sentinel surveillance based method: addition of substantial unnecessary HIV estimates from STI clinics, the common practice of referral of HIV positive/suspect patients by private practitioners to public hospitals, and a preferential use of public hospitals by lower socioeconomic strata. We derived conservative correction factors for the sentinel surveillance data and titrated these to the four major HIV states in India (Andhra Pradesh, Maharashtra, Karnataka and Tamil Nadu), and examined the impact on the overall HIV estimate for India. RESULTS: HIV data from STI clinics are not used elsewhere in the world as a component of HIV burden estimation in generalised epidemics, and the Guntur study verified that this was unnecessary. The referral of HIV positive/suspect patients from the private to the public sector is a widespread phenomenon in India, which is likely causing an upward distortion in HIV estimates from sentinel surveillance in other parts of India as well. Analysis of data from the nationwide Reproductive and Child Health Survey revealed that lower socioeconomic strata were over-represented among women seeking antenatal care at public hospitals in all major south Indian states, similar to the trend seen in the Guntur study. Application of conservative correction factors derived from the Guntur study reduced the 2005 official sentinel surveillance based HIV estimate of 3.7 million 15–49 years old persons in the four major states to 1.5–2.0 million, which would drop the official total estimate of 5.2 million 15–49 years old persons with HIV in India to 3–3.5 million. CONCLUSION: Plausible and cautious extrapolation of the trends seen in a recent large and rigorous population-based study of HIV in a south Indian district suggests that India is likely grossly overestimating its HIV burden with the current official sentinel surveillance based method. This method needs revision

A population-based study of human immunodeficiency virus in south India reveals major differences from sentinel surveillance-based estimates

BACKGROUND: The human immunodeficiency virus (HIV) burden among adults in India is estimated officially by direct extrapolation of annual sentinel surveillance data from public-sector antenatal and sexually transmitted infection (STI) clinics and some high-risk groups. The validity of these extrapolations has not been systematically examined with a large sample population-based study. METHODS: We sampled 13838 people, 15–49 years old, from 66 rural and urban clusters using a stratified random method to represent adults in Guntur district in the south Indian state of Andhra Pradesh. We interviewed the sampled participants and obtained dried blood spots from them, and tested blood for HIV antibody, antigen and nucleic acid. We calculated the number of people with HIV in Guntur district based on these data, compared it with the estimate using the sentinel surveillance data and method, and analysed health services use data to understand the differences. RESULTS: In total, 12617 people (91.2% of the sampled group) gave a blood sample. Adjusted HIV prevalence was 1.72% (95% confidence interval 1.35–2.09%); men 1.74% (1.27–2.21%), women 1.70% (1.36–2.04%); rural 1.64% (1.10–2.18%), urban 1.89% (1.39–2.39%). HIV prevalence was 2.58% and 1.20% in people in the lower and upper halves of a standard of living index (SLI). Of women who had become pregnant during the past 2 years, 21.1% had used antenatal care in large public-sector hospitals participating in sentinel surveillance. There was an over-representation of the lowest SLI quartile (44.7%) in this group, and 3.61% HIV prevalence versus 1.08% in the remaining pregnant women. HIV prevalence was higher in that group even when women were matched for the same SLI half (lower half 4.39%, upper 2.63%) than in the latter (lower 1.06%, upper 1.05%), due to referral of HIV-positive/suspected women by private practitioners to public hospitals. The sentinel surveillance method (HIV prevalence: antenatal clinic 3%, STI clinic 22.8%, female sex workers 12.8%) led to an estimate of 112635 (4.38%) people with HIV, 15–49 years old, in Guntur district, which was 2.5 times the 45942 (1.79%) estimate based on our population-based study. CONCLUSION: The official method in India leads to a gross overestimation of the HIV burden in this district due to addition of substantial extra HIV estimates from STI clinics, the common practice of referral of HIV-positive/suspected people to public hospitals, and a preferential use of public hospitals by people in lower socioeconomic strata. India may be overestimating its HIV burden with the currently used official estimation method

Initial Commitment to Pre-Exposure Prophylaxis and Circumcision for HIV Prevention amongst Indian Truck Drivers

Studies of HIV prevention interventions such as pre-exposure prophylaxis (PREP) and circumcision in India are limited. The present study sought to investigate Indian truck-drivers initial commitment to PREP and circumcision utilizing the AIDS Risk Reduction Model. Ninety truck-drivers completed an in-depth qualitative interview and provided a blood sample for HIV and HSV-2 testing. Truck-drivers exhibited low levels of initial commitment towards PREP and even lower for circumcision. However, potential leverage points for increasing commitment were realized in fear of infecting family rather than self, self-perceptions of risk, and for PREP focusing on cultural beliefs towards medication and physicians. Cost was a major barrier to both HIV prevention interventions. Despite these barriers, our findings suggest that the ARRM may be useful in identifying several leverage points that may be used by peers, health care providers and public health field workers to enhance initial commitment to novel HIV prevention interventions in India

Telehealth services in an outpatient nephrology clinic during the COVID-19 pandemic: a patient perspective

PURPOSE: In response to the COVID-19 pandemic, new policy waivers permitted reimbursement of telehealth services in urban settings. The aim of this study was to assess patient satisfaction with telehealth services during the COVID-19 pandemic in an outpatient urban nephrology practice. METHODS: Patients who had virtual encounters were asked to complete an online survey regarding their experiences with telehealth services. RESULTS: Twenty-one percent of eligible patients completed the survey. Patients (83.6%) reported overall positive experiences with telehealth and want to see a hybrid healthcare model in the future (80.1%). Additionally, most patients found telehealth appointments convenient to make and telehealth encounters convenient to conduct. Ethnicity, age, gender, and insurance type did not have a statistically significant impact on satisfaction ratings. Technical issues were not encountered by 79.5% of patients and patients were willing to use the video feature. However, if they had technical issues, patient satisfaction ratings were negatively impacted. CONCLUSION: Telehealth services are beneficial to patients with regards to convenience, decreased transportation costs and time, increased accessibility to healthcare, and decreased overall opportunity costs. However, challenges still remain with the deployment of telehealth and will be dependent on patients\u27 digital health literacy, access to broadband internet and devices, and legislation and/or regulations. Limitations of the study, including small sample size and surveying patients from a nephrology practice, may prevent it from being generalizable. Additional studies with a larger sample size and multiple specialties may be needed to generalize patients\u27 satisfaction with telehealth services