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Background: Human immunodeficiency virus (HIV) remains a global challenge and novel measures for transmission disruption are needed. Contact tracing is limited by reluctance or inability of newly diagnosed individuals to name at-risk contacts. Molecular cluster analysis is mostly used for outbreak investigations, and its role in routine public health activities remains uncertain., Methods: We conducted a 2-year prospective statewide study in Rhode Island to evaluate integration of HIV cluster analyses into routine contact tracing, by attempting to reinterview all new diagnoses who clustered, notifying them of clustering, and evaluating benefits of this strategy. Clustering was compared between a phylogenetic ensemble versus distance-based HIV-TRACE., Results: Of 100 new diagnoses during 2021-2022, 52 individuals clustered, of whom only 31% were reinterviewed. Reinterviewing did not improve contact tracing beyond initial interviews, and the study was stopped early for futility. Clustering concordance within the phylogenetic ensemble was high (88%-89%), but lower (74%) for HIV-TRACE. Despite hypothesis rejection, we established a public health-academic partnership, developed a bioinformatics pipeline enabling near real-time cluster analysis, and identified gaps and unique opportunities for intervention., Conclusions: Attempting to reinterview all statewide new HIV diagnoses in molecular clusters showed no evidence of improving contact tracing. However, a strong academic-public health partnership enabled near real-time, longitudinal integration of molecular cluster analysis into routine public health activities, and identified barriers and opportunities tailoring data-driven approaches to unique individual and community characteristics, guiding future work on optimal use of molecular epidemiology to disrupt HIV transmission., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The extent of the SARS-CoV-2 short-term evolution under Remdesivir (RDV) exposure and whether it varies across different upper respiratory compartments are not fully understood., Methods: Patients hospitalized for COVID-19, with or without RDV therapy, were enrolled and completed up to three visits, in which they provided specimens from four respiratory compartments. Near full-length genome SARS-CoV-2 sequences were obtained from viral RNA, standard lineage and variant assignments were performed, and viral mutations in the RNA-dependent RNA polymerase (RdRp) region-the RDV target gene-were detected and compared between participants with and without RDV, across the four compartments, within participants across visits, and versus a larger sequence dataset. The statistical analysis used a generalized linear mixed-effects model., Results: A total of 139 sequences were obtained from 37 out of the 44 (84%) enrolled participants. The genotyping success varied across respiratory compartments, which ranged from 42% with oropharyngeal specimens to 67% with nasopharyngeal specimens and showed improvement with higher viral loads. No RdRp mutations known to be associated with RDV resistance were identified, and for 34 detected mutations at 32 amino acid positions that are not known as RDV-associated, there was no evidence of any associations with the RDV exposure, respiratory compartment, or time. At least 1 of these 34 mutations were detected in all participants, and some differed from the larger sequence dataset., Conclusions: This study highlighted the SARS-CoV-2 short-term genomic stability within hosts and across upper respiratory compartments, which suggests a lack of evolution of RDV resistance over time. This contributes to our understanding of SARS-CoV-2 genomic dynamics.

Background: The use of molecular HIV cluster analysis to supplement public health contact tracing has shown promise in addressing HIV outbreaks. However, the potential of HIV cluster analysis as an adjunct to daily, person-by-person HIV prevention efforts remains unknown. We documented lessons learned within a unique public health-academic partnership while guiding workaday HIV prevention efforts with near-real-time molecular cluster analysis., Setting: A public health-academic partnership in the State of Rhode Island, the United States., Methods: We recorded perceptions of our team of academicians and public health practitioners that were encountered in an 18-month study evaluating the integration of molecular cluster analysis with HIV contact tracing for public health benefit. The focus was on monthly conferences where molecular clustering of each new statewide diagnosis was discussed to facilitate targeted interventions and on attempted reinterviews of all newly HIV-diagnosed persons statewide whose HIV sequences clustered to increase partner naming., Results: Three main themes emerged: First, multidisciplinary conferences are substantially beneficial for gleaning actionable inferences from integrating molecular cluster analysis and public health data. Second, universal reinterviews were perceived to potentially have negative consequences but may be selectively beneficial. Third, the translation of cluster analysis into public health action is hampered by jurisdictional surveillance boundaries and within-jurisdictional data silos, across which data sharing is problematic., Conclusions: Insights from a statewide public health-academic partnership support integration of molecular HIV cluster analyses with public health efforts, which can guide public health activities to prevent transmission while identifying substantial barriers to integration, informing continued research., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The technetium-99m methylene diphosphonate ( 99m Tc-MDP) whole-body bone scan along with single-photon emission computed tomography (SPECT/CT) can detect challenging soft tissue uptake patterns. We present a case of a 67-year-old female in whom the 99m Tc-MDP scan, performed 3 hours after injection, revealed abnormal soft tissue uptake in the right thoracic region. No functioning right kidney was seen in the right lumbar region. Hybrid SPECT/CT revealed an ectopic right kidney in the subdiaphragmatic location, accompanied by gut loops and eventration of the right-sided diaphragm. This case underscores the value of SPECT/CT in identifying and characterizing unexpected anatomical abnormalities, such as ectopic kidneys., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Korean Society of Nuclear Medicine 2023.)

Metal matrix composites (MMCs) have wide applications due to being lightweight, their high strength, and immense resistance to wear. To explore new generation materials like aluminum-based metal matrix composites (AMCs) for wide engineering applications, the present work aimed at investigating the effect of changes in composition, sintering time, and temperature on the hardness and surface roughness of AMCs containing SiC and ZrSiO 4 in wt % of 5, 20, 30, and 40 binary and hybrid sample pallets. The samples have been prepared by powder metallurgy (PM) method under 1000 psi pressure. After compaction, the above pallets sintered at different temperatures ranging from 500 °C to 1100 °C with an increment of 200 °C and 15 min intervals for four levels of temperature and time, respectively. Afterwards, sensitivity analysis has been done by investigating the effect of chemical composition, sintering time, and sintering temperature of the binary and hybrid composites on hardness and surface roughness. Morphological studies on the composites were carried out using field emission scanning electron microscope (FESEM) with energy dispersive spectroscopy (EDS). It has been observed that hardness is increased by increasing the sintering temperature in the case of SiC, whereas surface roughness did not change much by changing the composition. Additionally, a rise in temperature lead to liquid-state sintering. SEM images obtained during the elemental analysis showed that porosity is generated within the samples after sintering due to the higher melting point of reinforcements compared to a base metal, i.e., aluminum. Mathematical equations have also been developed via regression analysis using Minitab and excel for the confirmation and validation of experimental data. Analysis of Variance (ANOVA) has also been done, and its tables are shown and discussed in the paper. Hence, the most optimized findings relating the changes in the composition of reinforcements, sintering temperature, and sintering time (input variables) with porosity, hardness, and surface roughness have been presented in the current study.

The electrical discharge machining (EDM) process is one of the most efficient non-conventional precise material removal processes. It is a smart process used to intricately shape hard metals by creating spark erosion in electroconductive materials. Sparking occurs in the gap between the tool and workpiece. This erosion removes the material from the workpiece by melting and vaporizing the metal in the presence of dielectric fluid. In recent years, EDM has evolved widely on the basis of its electrical and non-electrical parameters. Recent research has sought to investigate the optimal machining parameters for EDM in order to make intricate shapes with greater accuracy and better finishes. Every method employed in the EDM process has intended to enhance the capability of machining performance by adopting better working conditions and developing techniques to machine new materials with more refinement. This new research aims to optimize EDM's electrical parameters on the basis of multi-shaped electrodes in order to obtain a good surface finish and high dimensional accuracy and to improve the post-machining hardness in order to improve the overall quality of the machined profile. The optimization of electrical parameters, i.e., spark voltage, current, pulse-on time and depth of cut, has been achieved by conducting the experimentation on die steel D2 with a specifically designed multi-shaped copper electrode. An experimental design is generated using a statistical tool, and actual machining is performed to observe the surface roughness, variations on the surface hardness and dimensional stability. A full factorial design of experiment (DOE) approach has been followed (as there are more than two process parameters) to prepare the samples via EDM. Regression analysis and analysis of variance (ANOVA) for the interpretation and optimization of results has been carried out using Minitab as a statistical tool. The validation of experimental findings with statistical ones confirms the significance of each operating parameter on the output parameters. Hence, the most optimized relationships were found and presented in the current study.

COVID-19 is an infectious disease that caused a global pandemic affecting people worldwide. As disease detection and vaccine rollout continue to progress, there is still a need for efficient diagnostic tools to satisfy continued testing needs. This preliminary study evaluated a novel SARS-CoV-2 diagnostic test called DirectDetect SARS-CoV-2 Direct Real-time reverse transcriptase polymerase chain reaction (RT-PCR) based on a limited sample size of 24 respiratory samples from 14 SARS-CoV-2-positive patients. The test is advantageous compared to others on the market since it does not require viral transport medium or viral RNA extraction prior to nucleic acid amplification and detection. This capability transforms the hours-long sample preparation time into a minutes-long procedure while also eliminating the need for many costly reagents which may be difficult to obtain during the surge in nucleic acid-based testing during the pandemic. The results show a positive agreement of 94.7, 100, and 94.7% between dry sample swabs, treated samples, and untreated samples tested using the DirectDetect SARS-CoV-2 Direct Real-time RT-PCR compared to tests used in a clinical laboratory, respectively. The findings indicate that DirectDetect can be used for multiple different sample types while reducing the number of reagents and time needed for diagnosis. Although this study shows promising results using the DirectDetect results, further validation of this test using a larger sample set is required to assess the true performance of this test., Competing Interests: The authors declare the following competing financial interest(s): AT is a paid scientific advisor/consultant and lecturer for PerkinElmer. RK and CGB received research funding from Gilead Sciences that supported sample collection, though the funding was not related to this research and the funder did not have any input on the research., (© 2022 The Authors. Published by American Chemical Society.)

Great efforts are devoted to end the HIV epidemic as it continues to have profound public health consequences in the United States and throughout the world, and new interventions and strategies are continuously needed. The use of HIV sequence data to infer transmission networks holds much promise to direct public heath interventions where they are most needed. As these new methods are being implemented, evaluating their benefits is essential. In this paper, we recognize challenges associated with such evaluation, and make the case that overcoming these challenges is key to the use of HIV sequence data in routine public health actions to disrupt HIV transmission networks., Competing Interests: Competing interests: Authors state no conflict of interest.

Rationale: Human immunodeficiency virus (HIV) infection is a risk factor for pulmonary hypertension (PH). Chronic hepatitis C virus (HCV) infection may have unique or synergistic effects on the pulmonary vasculature, but the prevalence and risk factors for PH in HIV-HCV coinfected persons are not known., Objectives: To define the prevalence of echocardiographic PH in a cohort of patients with HIV-HCV coinfection, to compare this estimate with the reported prevalence of PH among those with HIV infection alone, and to identify potential risk factors for PH in coinfected individuals., Methods: We performed a retrospective study of HIV-HCV coinfected patients followed at our institution from 2003 to 2012 with evidence of HCV infection (positive HCV antibody, measurable HCV ribonucleic acid viral load, and/or genotype) within 6 months of transthoracic echocardiogram. PH was defined by an estimated pulmonary artery systolic pressure (PASP) of greater than or equal to 40 mm Hg or more than moderate right ventricular dysfunction. We excluded those diagnosed with cirrhosis, left ventricular ejection fraction less than 50%, or more than moderate aortic or mitral valve disease., Measurements and Main Results: Sixty-eight patients were included, and 43 had adequate estimates of PASP. The median (interquartile range) age was 52 (48-57) years, and 45 (67%) were men. Eight (19%) had PH, and three (7%) had more than moderate right ventricular dysfunction. After age and sex adjustment, interferon (IFN)-based HCV treatment was associated with higher PASP (β, 6.00 mm Hg; 95% confidence interval, 0.09-11.90; P = 0.047) and with the risk of PH (odds ratio, 5.65; 95% confidence interval, 1.07-29.93; P = 0.042). These associations persisted after adjustment for comorbidities but were attenuated by adjustment for duration of HCV diagnosis., Conclusions: The prevalence of echocardiographic PH may be higher in HIV-HCV coinfected individuals than in those with HIV monoinfection. IFN-based HCV treatment and time since HCV diagnosis were associated with the development of PH as assessed by echocardiography. Further studies are needed to examine HIV-HCV coinfection, HCV treatment, and duration of infection as possible causes of pulmonary vascular disease.

To successfully implement the Seek, Test, and Treat (STT) strategy to curb the HIV epidemic, the criminal justice system must be a key partner. Increasing HIV testing and treatment among incarcerated persons has the potential to decrease HIV transmission in the broader community, but whether it is feasible to consider the implementation of the STT within jail facilities is not known. We conducted a retrospective review of Rhode Island Department of Corrections (RIDOC) medical records to assess whether persons newly diagnosed in the jail were able to start ART and be linked to community HIV care after release. From 2001 to 2007, 64 RIDOC detainees were newly diagnosed with HIV. During their index incarcerations, 64% were informed of positive confirmatory HIV test results, 50% completed baseline evaluations, and 9% began ART. Linkage to community care was confirmed for 58% of subjects. Subjects incarcerated for >14 days were significantly more likely to receive HIV test results and complete baseline evaluation (p<0.001). A similar association was not observed for ART initiation until incarceration length reached 60 days (p<0.001). There was no association between incarceration length and linkage to care. This comprehensive analysis demonstrates that length of incarceration impacts HIV test result delivery, baseline evaluation, and ART initiation in the RIDOC. Jails are an important venue to "Seek" and "Test"; however, completing the "Treat" part of the STT strategy is hindered by the transient nature of this criminal justice population and may require new strategies to improve linkage to care.

Long-term potentiation (LTP) of excitatory afferents to the dorsal striatum likely occurs with learning to encode new skills and habits, yet corticostriatal LTP is challenging to evoke reliably in brain slice under physiological conditions. Here we test the hypothesis that stimulating striatal afferents with theta-burst timing, similar to recently reported in vivo temporal patterns corresponding to learning, evokes LTP. Recording from adult mouse brain slice extracellularly in 1 mM Mg(2+), we find LTP in dorsomedial and dorsolateral striatum is preferentially evoked by certain theta-burst patterns. In particular, we demonstrate that greater LTP is produced using moderate intraburst and high theta-range frequencies, and that pauses separating bursts of stimuli are critical for LTP induction. By altering temporal pattern alone, we illustrate the importance of burst-patterning for LTP induction and demonstrate that corticostriatal long-term depression is evoked in the same preparation. In accord with prior studies, LTP is greatest in dorsomedial striatum and relies on N-methyl-d-aspartate receptors. We also demonstrate a requirement for both Gq- and Gs/olf-coupled pathways, as well as several kinases associated with memory storage: PKC, PKA, and ERK. Our data build on previous reports of activity-directed plasticity by identifying effective values for distinct temporal parameters in variants of theta-burst LTP induction paradigms. We conclude that those variants which best match reports of striatal activity during learning behavior are most successful in evoking dorsal striatal LTP in adult brain slice without altering artificial cerebrospinal fluid. Future application of this approach will enable diverse investigations of plasticity serving striatal-based learning.

New HIV infections among younger men who have sex with men (MSM) in the United States are escalating. Data on HIV infections in college students are limited. In 2010, three MSM college students presented to our clinic with primary HIV infection (PHI) in a single month. To determine the number of college students among new HIV diagnoses, we reviewed clinical characteristics and molecular epidemiology of HIV-diagnosed individuals from January to December 2010 at the largest HIV clinic in Southern New England. PHI was defined as acute HIV infection or seroconversion within the last 6 months. Of 66 individuals diagnosed with HIV in 2010, 62% were MSM and 17% were academic students (12% college or university, 5% other). Seventy-three percent of students were MSM. Compared to nonstudents, students were more likely to be younger (24 versus 39 years), born in the United States (91% versus 56%), have another sexually transmitted disease (45% versus 11%), and present with PHI (73% versus 16%, all p-values<0.05). Thirty percent of individuals formed eight transmission clusters including four students. MSM were more likely to be part of clusters. Department of Health contact tracing of cluster participants allowed further identification of epidemiological linkages. Given these high rates of PHI in recently diagnosed students, institutions of higher education should be aware of acute HIV presentation and the need for rapid diagnosis. Prevention strategies should focus on younger MSM, specifically college-age students who may be at increased risk of HIV infection.

The basal ganglia is a brain region critically involved in reinforcement learning and motor control. Synaptic plasticity in the striatum of the basal ganglia is a cellular mechanism implicated in learning and neuronal information processing. Therefore, understanding how different spatio-temporal patterns of synaptic input select for different types of plasticity is key to understanding learning mechanisms. In striatal medium spiny projection neurons (MSPN), both long term potentiation (LTP) and long term depression (LTD) require an elevation in intracellular calcium concentration; however, it is unknown how the post-synaptic neuron discriminates between different patterns of calcium influx. Using computer modeling, we investigate the hypothesis that temporal pattern of stimulation can select for either endocannabinoid production (for LTD) or protein kinase C (PKC) activation (for LTP) in striatal MSPNs. We implement a stochastic model of the post-synaptic signaling pathways in a dendrite with one or more diffusionally coupled spines. The model is validated by comparison to experiments measuring endocannabinoid-dependent depolarization induced suppression of inhibition. Using the validated model, simulations demonstrate that theta burst stimulation, which produces LTP, increases the activation of PKC as compared to 20 Hz stimulation, which produces LTD. The model prediction that PKC activation is required for theta burst LTP is confirmed experimentally. Using the ratio of PKC to endocannabinoid production as an index of plasticity direction, model simulations demonstrate that LTP exhibits spine level spatial specificity, whereas LTD is more diffuse. These results suggest that spatio-temporal control of striatal information processing employs these Gq coupled pathways.

Meeting the needs of HIV-infected pregnant women requires understanding their backgrounds and potential barriers to care and safe pregnancy. Foreign-born women are more likely to have language, educational, and economic barriers to care, but may be even more likely to choose to keep a pregnancy. Data from HIV-infected pregnant women and their children in Rhode Island were analyzed to identify trends in demographics, viral control, terminations, miscarriages, timing of diagnosis, and adherence to followup. Between January 2004 and December 2009, 76 HIV-infected women became pregnant, with a total of 95 pregnancies. Seventy-nine percent of the women knew their HIV status prior to becoming pregnant. Fifty-four percent of the women were foreign-born and 38 percent of the 16 women who chose to terminate their pregnancies were foreign-born. While the number of HIV-infected women becoming pregnant has increased only slightly, the proportion that are foreign-born has been rising, from 41 percent between 2004 and 2005 to 57.5 percent between 2006 and 2009. A growing number of women are having multiple pregnancies after their HIV diagnosis, due to the strength of their desire for childbearing and the perception that HIV is a controllable illness that does not preclude the creation of a family.

Objectives: The number of HIV-infected refugees entering the USA is increasing. There is little data describing the HIV-infected refugee population and the challenges encountered when caring for them. We performed a retrospective case-control analysis of HIV-infected refugees in order to characterize their co-morbidities, baseline HIV characteristics, and longitudinal care compared to HIV-infected non-refugees., Methods: A retrospective chart review was performed of HIV-infected refugees and non-refugees who were matched for gender, age, and time of establishment of initial HIV care., Results: The refugee population studied was largely from West Africa. Refugees were more likely than non-refugees to have heterosexual risk for HIV infection, latent tuberculosis infection, and active hepatitis B. Refugees were less likely than non-refugees to have a history of substance use, start antiretrovirals, and be enrolled in a clinical study. The baseline CD4 counts and HIV plasma viral loads were similar between the two groups., Conclusions: Clinicians caring for West African HIV-infected refugees should be knowledgeable about likely co-morbidities and the impact of cultural differences on HIV care. Further studies are needed to develop culturally competent HIV treatment, education, and prevention programs for refugees who are beginning a new life in the USA.

Objective: To assess the level of knowledge about skin cancer in youth and to explore the influence of gender and system of education on their knowledge and practices., Materials and Methods: A questionnaire-based study was conducted at The Aga Khan University Medical College (AKUMC), on Year 2 pre-clinical medical students. Descriptive analyses to examine the frequency distribution, chi-square test and factor analysis were applied using SPSS., Results: Seventyone students participated in the study; 90% scored > 55% in the questions regarding knowledge of Malignant melanoma (MM), whereas in the questions assessing practice only 11% of the respondents scored > 52%. They were largely unaware that appearance of a new mole is a risk factor for MM (56% respondents incorrect) and that skin cancer is one of the most common cancers (54% respondents incorrect). 73% reported being sunburned at least once during childhood and 40% suffered sunburns at least once this summer, which points to the inadequacy of sun protection. The risk of MM may double if severe sunburns are experienced during childhood. Education system and gender did not affect the knowledge and practices. The popular sources of learning about skin cancer were magazines (52%) followed by television (42%)., Conclusion: There is a need for epidemiological studies in Pakistani population regarding skin cancer. For preventing excessive solar exposure which leads to sunburns, we recommend interventions like a Pilot Program for photoprotection education and Sun Awareness Week to improve knowledge and sun protection behavior.