A neutralizing antibody target in early HIV-1 infection was recapitulated in rhesus macaques immunized with the transmitted/founder envelope sequence.

Transmitted/founder (T/F) HIV-1 envelope proteins (Envs) from infected individuals that developed neutralization breadth are likely to possess inherent features desirable for vaccine immunogen design. To explore this premise, we conducted an immunization study in rhesus macaques (RM) using T/F Env sequences from two human subjects, one of whom developed potent and broad neutralizing antibodies (Z1800M) while the other developed little to no neutralizing antibody responses (R66M) during HIV-1 infection. Using a DNA/MVA/protein immunization protocol, 10 RM were immunized with each T/F Env. Within each T/F Env group, the protein boosts were administered as either monomeric gp120 or stabilized trimeric gp140 protein. All vaccination regimens elicited high titers of antigen-specific IgG, and two animals that received monomeric Z1800M Env gp120 developed autologous neutralizing activity. Using early Env escape variants isolated from subject Z1800M as guides, the serum neutralizing activity of the two immunized RM was found to be dependent on the gp120 V5 region. Interestingly, the exact same residues of V5 were also targeted by a neutralizing monoclonal antibody (nmAb) isolated from the subject Z1800M early in infection. Glycan profiling and computational modeling of the Z1800M Env gp120 immunogen provided further evidence that the V5 loop is exposed in this T/F Env and was a dominant feature that drove neutralizing antibody targeting during infection and immunization. An expanded B cell clonotype was isolated from one of the neutralization-positive RM and nmAbs corresponding to this group demonstrated V5-dependent neutralization similar to both the RM serum and the human Z1800M nmAb. The results demonstrate that neutralizing antibody responses elicited by the Z1800M T/F Env in RM converged with those in the HIV-1 infected human subject, illustrating the potential of using immunogens based on this or other T/F Envs with well-defined immunogenicity as a starting point to drive breadth.

Unveiling Barriers to the Modern Contraceptive Uptake in the Urban Slums of Karachi: Perceptions, Attitude, and Accessibility.

Background Modern contraception plays a vital role in family planning and preventing unintended pregnancies. However, its uptake remains limited in many developing countries, including Pakistan. This study aimed to evaluate the barriers to modern contraception and identify strategies to enhance its adoption in the urban slums of Karachi. Methods A multi-site, cross-sectional study was conducted in 38 slum areas of Karachi, Pakistan. Women aged 15-49 years were interviewed using a comprehensive questionnaire. The questionnaire covered socio-ethnic and economic demographics, knowledge and perceptions of modern contraception, accessibility, affordability, attitudes, and usage. Data analysis was performed using the Statistical Package for Social Sciences (SPSS) version 24 (IBM SPSS Statistics, Armonk, NY). Results The majority of the respondents identified as Pathan ethnicity (49%), and the age range was predominantly from 23 to 34 years (45.5%). A high proportion of participants demonstrated satisfactory knowledge of contraceptives (87.6%). However, a significant portion perceived contraception or family planning to be in conflict with religious beliefs (84%). Many women expressed a desire for more children (56%) and had concerns about contraceptive side effects (78%). A notable proportion of women reported that their spouses forbade the use of contraceptives (12%). Among the surveyed population, the most widely used contraceptives were injections among women (15.5%) and condoms among their male partners (12%). Conclusion Despite sufficient knowledge and accessibility, considerable barriers exist in the uptake of modern contraception in the urban slums of Karachi, Pakistan. These barriers include religious conflicts, cultural norms, concerns about side effects, spousal disapproval, and desires for larger families.

Joint analyses by laser-induced breakdown spectroscopy (LIBS) and Raman spectroscopy at stand-off distances.

Raman spectroscopy and laser-induced breakdown spectroscopy (LIBS) of solid samples have both been shown to be feasible with sample-to-instrument distances of many meters. The two techniques are very useful together, as the combination of elemental compositions from LIBS and molecular vibrational information from Raman spectroscopy strongly complement each other. Remote LIBS and Raman spectroscopy spectra were taken together on a number of mineral samples including sulfates, carbonates and silicates at a distance of 8.3 m. The complementary nature of these spectra is highlighted and discussed. A factor of approximately 20 difference in intensity was observed between the brightest Raman line of calcite, at optimal laser power, and the brighter Ca I LIBS emission line measured with 55 mJ/pulse laser power. LIBS and Raman spectroscopy have several obstacles to devising a single instrument capable of both techniques. These include the differing spectral ranges and required detection sensitivity. The current state of technology in these areas is discussed.

Anterior spinal cord syndrome of unknown etiology.

A spinal cord injury encompasses a physical insult to the spinal cord. In the case of anterior spinal cord syndrome, the insult is a vascular lesion at the anterior spinal artery. We present the cases of two 13-year-old boys with anterior spinal cord syndrome, along with a review of the anatomy and vasculature of the spinal cord and an explanation of how a lesion in the cord corresponds to anterior spinal cord syndrome.

An assessment of emergency medicine residents' ability to perform in a multitasking environment.

PURPOSE: Multitasking (MT) is a term often applied to emergency medicine (EM), but it is still poorly understood. In an effort to facilitate MT research in EM, the authors conducted this pilot study to describe EM residents' scores on a Multi-Tasking Assessment Tool (MTAT) and compare these scores with the residents' work efficiency in the emergency department. METHOD: The authors administered a previously developed test of MT ability to EM residents. They performed a multiple regression analysis to determine the effect of MT ability on resident work efficiency, defining efficiency as the number of relative value units billed per hour. They controlled the analysis for year of training and medical knowledge using as a standard the in-service exam administered by the American Board of Emergency Medicine. RESULTS: Complete data for 35 residents were available for analysis. Work efficiency was multivariately correlated with MTAT scores and year of training (P < .05). Whereas year of training explained the majority of the variance, a resident's MT ability accounted for a smaller but still significant portion. CONCLUSIONS: This pilot study further validates the MTAT and lays the groundwork for further research in MT in EM. Resident year of training and MTAT scores explain the variability in resident work efficiency significantly more than medical knowledge. Understanding MT ability may ultimately help in resident selection, education, and remediation as well as career counseling and improvement of practice systems in EM.