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Background: Pre-exposure prophylaxis (PrEP) is an important tool for HIV prevention in Latin America and the Caribbean (LAC). Yet, little is known about the PrEP policies landscape in the region. Addressing this gap, this scoping review assessed current PrEP policies throughout LAC to better understand existing PrEP implementation gaps and identify opportunities to improve access. Methods: We conducted a scoping review, using a modified PRISMA extension, through 28 July 2022, to identify country-level PrEP policies. Data were collected in English, Spanish, French, and Portuguese utilizing online platforms for screening and data extraction (Google Forms, Zotero, and Excel). Extracted data were divided by data source, including country-level government policies, gray literature, and peer-reviewed literature, with at least one full-text reviewer and data extractor per publication. An iterative summative content analysis was performed to compare and interpret themes across phases and data sources. Results: Of the 33 countries in LAC, 22 (67%) had policies approving daily oral PrEP for HIV prevention, which outlined specific key populations, including men who have sex with men, transgender women, sex workers, and serodiscordant couples. Generic tenofovir disoproxil fumarate/emtricitabine has been approved in 15 of the 33 countries, and 13 of the 33 countries have incorporated PrEP into their public health system. No countries were found to have approved cabotegravir. Costing data were reported by only one country, Ecuador, in its national health ministry guidelines. Findings also document a lag between the media/gray-literature announcement of PrEP and implementation of policies. Conclusion: Findings underscore significant advances in PrEP policies in the region and signal opportunities for greater PrEP implementation. Since 2017, an increasing number of countries have begun to provide PrEP to communities at heightened need, although significant gaps remain. Policy approval is a key step to further increasing access to PrEP in LAC, necessary to reduce the burden of HIV in LAC, specifically among marginalized populations.

The intrinsic cardiac nervous system (ICNS) is composed of interconnected clusters of neurons called ganglionated plexi (GP) which play a major role in controlling heart rate and rhythm. The function of these neurons is particularly important due to their involvement in cardiac arrhythmias such as atrial fibrillation (AF), and previous work has shown that plasticity in GP neural networks could underpin aberrant activity patterns that drive AF. As research in this field increases, developing new techniques to visualize the complex interactions and plasticity in this GP network is essential. In this study we have developed a calcium imaging method enabling the simultaneous recording of plasticity in neuronal activity from multiple neurons in intact atrial GP networks. Calcium imaging was performed with Cal-520 AM labeling in aged spontaneously hypertensive rats (SHRs), which display both spontaneous and induced AF, and age-matched Wistar Kyoto (WKY) controls to determine the relationship between chronic hypertension, arrhythmia and GP calcium dynamics. Our data show that SHR GPs have significantly larger calcium responses to cholinergic stimulation compared to WKY controls, as determined by both higher amplitude and longer duration calcium responses. Responses were significantly but not fully blocked by hexamethonium, indicating multiple cholinergic receptor subtypes are involved in the calcium response. Given that SHRs are susceptible to cardiac arrhythmias, our data provide evidence for a potential link between arrhythmia and plasticity in calcium dynamics that occur not only in cardiomyocytes but also in the GP neurons of the heart.

Constructing multiplicative reasoning is critical for students' learning of mathematics, particularly throughout the middle grades and beyond. Tzur, Xin, Si, Kenney, and Guebert [American Educational Research Association, ERIC No. ED510991, (2010)] conclude that an assimilatory composite unit is a conceptual spring to multiplicative reasoning. This study examines patterns in the percentages of students who construct multiplicative reasoning across the middle grades based on their fluency in operating with composite units. Multinomial logistic regression models indicate that students' rate of constructing an assimilatory composite unit but not multiplicative reasoning in sixth and seventh grades is significantly greater than that in eighth and ninth grades. Furthermore, the proportion of students who have constructed multiplicative reasoning in sixth and seventh grades is significantly less than the proportion of those who have constructed multiplicative reasoning in eighth and ninth grades. One implication of this is the quantitative verification of Tzur, Xin, Si, Kenney, and Guebert's (2010) conceptual spring. That is, students who construct assimilatory composite units early in the middle grades are likely to construct multiplicative reasoning; students who do not construct assimilatory composite units early in the middle grades likely do not construct multiplicative reasoning in the middle grades.

Ras family proteins are membrane-bound GTPases that control proliferation, survival, and motility. Many forms of cancers are driven by the acquisition of somatic mutations in a RAS gene. In pancreatic cancer (PC), more than 90% of tumors carry an activating mutation in KRAS. Mutations in components of the Ras signaling pathway can also be the cause of RASopathies, a group of developmental disorders. In a subset of RASopathies, the causal mutations are in the LZTR1 protein, a substrate adaptor for E3 ubiquitin ligases that promote the degradation of Ras proteins. Here, we show that the function of LZTR1 is regulated by the glycogen synthase kinase 3 (GSK3). In PC cells, inhibiting or silencing GSK3 led to a decline in the level of Ras proteins, including both wild type Ras proteins and the oncogenic Kras protein. This decline was accompanied by a 3-fold decrease in the half-life of Ras proteins and was blocked by the inhibition of the proteasome or the knockdown of LZTR1. Irrespective of the mutational status of KRAS, the decline in Ras proteins was observed and accompanied by a loss of cell proliferation. This loss of proliferation was blocked by the knockdown of LZTR1 and could be recapitulated by the silencing of either KRAS or GSK3. These results reveal a novel GSK3-regulated LZTR1-dependent mechanism that controls the stability of Ras proteins and proliferation of PC cells. The significance of this novel pathway to Ras signaling and its contribution to the therapeutic properties of GSK3 inhibitors are both discussed.

Recent advancements in aqueous humor (AH) cell-free DNA (cfDNA) genomics have opened new avenues for ex vivo molecular profiling of retinoblastoma (RB), the most common pediatric intraocular malignancy, where biopsy is typically prohibited. While these insights offer a genetic blueprint of the tumor, they lack multi-omic molecular phenotyping, which is essential for understanding the functional state. Extracellular vesicles (EVs), naturally present in AH, are promising by offering time-resolved phenotypic information. We employed multiplex bead-based flow cytometry and Single Extracellular Vesicle Nanoscopy (SEVEN) to analyze EV phenotypes in AH from a cohort of five RB, with three uveal melanoma (UM) and two age-matched glaucoma (GLC) samples serving as controls. The studies identified CD133-enriched EVs uniquely in RB AH, absent in both GLC and UM AH. This was corroborated by further analysis of five RB cell lines, including two commercial (Y79, Weri) and three in-house developed lines, confirming CD133 enrichment and supporting its role as an RB-specific EV marker. Single-vesicle analysis demonstrated a strong association of CD133 with CD81 and CD63, with minimal CD9 presence. These results, validated through complementary techniques, position CD133 as a critical marker in RB-derived EVs, paving the way for enhanced multi-omic RB characterization and potential advancements in clinical diagnostics. [ABSTRACT FROM AUTHOR]

Simple Summary: The Yes-associated protein (YAP) is part of a system that regulates cell proliferation in response to changes in cell–cell and cell–matrix interactions. In malignant tumors, that system is almost always disrupted in ways that promote the stability of YAP. Mutations in genes encoding Ras proteins are found in 30% of all human cancers, but the mechanisms by which these mutated proteins promote cancer are still incompletely understood. Here, we investigated the regulation of YAP stability by the Ras oncogenes and found that while Ras does not directly regulate YAP, the stability of YAP is directly controlled by one of Ras's own effectors, the Rac1 GTPase, a small regulatory protein involved in controlling cell shape and migration. This regulation of YAP by Rac1 could potentially play an important role in the development of therapeutic resistance to Ras inhibitors, which we know can be promoted by the overexpression of YAP. Background: Oncogenic mutations in the KRAS gene are detected in >90% of pancreatic cancers (PC). In genetically engineered mouse models of PC, oncogenic KRAS drives the formation of precursor lesions and their progression to invasive PC. The Yes-associated Protein (YAP) is a transcriptional coactivator required for transformation by the RAS oncogenes and the development of PC. In Ras-driven tumors, YAP can also substitute for oncogenic KRAS to drive tumor survival after the repression of the oncogene. Ras oncoproteins exert their transforming properties through their downstream effectors, including the PI3K kinase, Rac1 GTPase, and MAPK pathways. Methods: To identify Ras effectors that regulate YAP, YAP levels were measured in PC cells exposed to inhibitors of oncogenic K-Ras and its effectors. Results: In PC cells, the inhibition of Rac1 leads to a time-dependent decline in YAP protein, which could be blocked by proteosome inhibitor MG132. This YAP degradation after Rac1 inhibition was observed in a range of cell lines using different Rac1 inhibitors, Rac1 siRNA, or expression of dominant negative Rac1T17N mutant. Several E3 ubiquitin ligases, including SCFβTrCP, regulate YAP protein stability. To be recognized by this ligase, the βTrCP degron of YAP (amino acid 383–388) requires its phosphorylation by casein kinase 1 at Ser384 and Ser387, but these events must first be primed by the phosphorylation of Ser381 by LATS1/2. Using Flag-tagged mutants of YAP, we show that YAP degradation after Rac1 inhibition requires the integrity of this degron and is blocked by the silencing of βTrCP1/2 and by the inhibition of casein kinase 1. Unexpectedly, YAP degradation after Rac1 inhibition was still observed after the silencing of LATS1/2 or in cells carrying a LATS1/2 double knockout. Conclusions: These results reveal Rac1 as an oncogenic KRAS effector that contributes to YAP stabilization in PC cells. They also show that this regulation of YAP by Rac1 requires the SCFβTrCP ligase but occurs independently of the LATS1/2 kinases. [ABSTRACT FROM AUTHOR]

Core temperature (TC) changes, alongside exercise, affect hemodynamic responses across different conduit and microvascular beds. This study investigated impacts of ecologically valid environmental heat and exercise exposures on cerebral, skin and retinal vascular responses by combining physiological assessments alongside computational fluid dynamics (CFD) modeling. Young, healthy participants (n = 12) were exposed to environmental passive heating (PH), and heated exercise (HE) (ergometer cycling), in climate-controlled conditions (50 mins, 40°C, 50% relative humidity) while maintaining upright posture. Blood flow responses in the common carotid (CCA), internal carotid (ICA) and central retinal (CRA) arteries were assessed using Duplex ultrasound, while forearm skin microvascular blood flow responses were measured using optical coherence tomography angiography. Three-dimensional retinal hemodynamics (flow and pressure) were calculated via CFD simulation, enabling assessment of wall shear stress (WSS). TC rose following PH (+0.2°C, p = 0.004) and HE (+1.4°C, p < 0.001). PH increased skin microvascular blood flow (p < 0.001), whereas microvascular CRA flow decreased (p = 0.038), despite unchanged ICA flow. HE exacerbated these differences, with increased CCA flow (p = 0.007), unchanging ICA flow and decreased CRA flow (p < 0.001), and interactions between vascular (CCA vs. ICA p = 0.018; CCA vs. CRA p = 0.004) and microvascular (skin vs. retinal arteriolar p < 0.001) territories. Simulations revealed patterns of WSS and lumen pressure that uniformly decreased following HE. Under ecologically valid thermal challenge, different responses occur in distinct conduit and microvascular territories, with blood flow distribution favoring systemic thermoregulation, while flow may redistribute within the brain. [ABSTRACT FROM AUTHOR]

Monitoring personal ultraviolet (UV) exposure facilitates risk mitigation against UV‐induced skin aging and skin cancer, the most common malignancy in North America, Europe, and Australia. UV radiometers convey real‐time information on local UV irradiance, while UV dosimeters count accumulated UV exposure over time. These devices can help users manage exposure levels in order to reach a healthy daily dose of UV light required for vitamin D production without exceeding erythemal limits that would increase skin cancer risk. However, personal UV detectors still suffer from several limitations. Wearable electronic UV sensors are relatively bulky, heavy, and expensive, while the more commonly used on‐skin disposable colorimetric UV sensors suffer from short service life, skin discomfort, and high accumulated costs when used daily as recommended. Intradermal colorimetric UV nanosensors can overcome these limitations, offering long‐term, comfortable, and inexpensive naked‐eye colorimetric indication of intradermal UV irradiance. Now, a new generation of UV‐sensing intradermal pigments with an improved design offers better tunability, stability, and biocompatibility. These UV‐photochromic nanosensors may be operated as UV dosimeters or simple sunscreen efficacy monitors, depending on the formulation, and can remain functional and re‐usable in the dermis for years. [ABSTRACT FROM AUTHOR]

Tick-borne infections are increasing in the United States and around the world. The most common tick-borne disease in the United States is Lyme disease caused by infection with the spirochete Borrelia burgdorferi (Bb), and pathogenesis varies from subclinical to severe. Bb infection is transmitted by Ixodes ticks, which can carry multiple other microbial pathogens, including Ehrlichia species. To address how the simultaneous inoculation of a distinct pathogen impacted the course of Bb-induced disease, we used C57BL/6 (B6) mice which are susceptible to Bb infection but develop only mild joint pathology. While infection of B6 mice with Bb alone resulted in minimal inflammatory responses, mice co-infected with both Bb and the obligate intracellular pathogen Ehrlichia muris (Em) displayed hematologic changes, inflammatory cytokine production, and emergency myelopoiesis similar to what was observed in mice infected only with Em. Moreover, infection of B6 mice with Bb alone resulted in no detectable joint inflammation, whereas mice co-infected with both Em and Bb exhibited significant inflammation of the ankle joint. Our findings support the concept that co-infection with Ehrlichia can exacerbate inflammation, resulting in more severe Bb-induced disease. [ABSTRACT FROM AUTHOR]

A worldwide increasing demand for renewable and non‐renewable energy resources has been ongoing since the mid‐1970s and is projected to increase for the next 2 decades. The effects of oil and natural gas development on wildlife mortality risk may play an important role in mule deer (Odocoileus hemionus) population dynamics. We evaluated the potential effects of oil and natural gas development on mortality risk of mule deer in western North Dakota and eastern Montana, USA. We assessed adult and juvenile female mule deer mortality risk with Poisson point process models using 265 deer fitted with global positioning system (GPS) radio‐collars that were deployed from 2013–2016. Mortality covariates included proportion of area disturbed by oil and natural gas development, distance to oil and natural gas development, distance to roads, temperature, snow depth, normalized difference vegetation index (NDVI), and age of deer. During the study there was no effect of oil and natural gas development or roads on mule deer mortality, though <1% of all deer locations were within 500 m of active drilling rigs. Mule deer mortality was greatest in winter and spring, and positively related to temperature during these seasons. Estimated annual adult survival probability was 0.79 (95% CI = 0.71–0.85). Given the strong influence of season and temperature variables on mortality risk, weather had the strongest influence on mule deer mortality during this study. Although we did not detect an effect of energy development on mule deer mortality, effects on space use resulting from development could influence deer dynamics in the region through displacement and could occur over longer time scales than we evaluated. This study can be used in pre‐development planning in a risk assessment framework to minimize effects of development on mule deer. [ABSTRACT FROM AUTHOR]

This study investigated the leap characteristics of rainbow trout (also known as steelhead) (Oncorhynchus mykiss) present in the Laurentian Great Lakes. To aid in the collection and annotation of leaps, a custom web application was developed and through the labeling of key markers, the launch speed, launch angle, and length of the fish were calculated. Data collection took place during migratory runs in the spring of 2022 and 2023 that resulted in 173 total leaps annotated with mean launch angles of 58.73 and 68.2 degrees, in 2022 and 2023, respectively. The mean launch speed normalized by body length was consistent across years at 8.6 body lengths per second. The integration of leaping data with computational fluid dynamics simulations revealed steelhead launch angle aligns closely with the water velocity direction as the velocity magnitude increases. Applications of this study include hazard analyses for unintended escapement and informed design of intelligent migratory barriers such as those to be developed at FishPass, an instream research facility under design for the Boardman (Ottaway) River in Traverse City, MI, USA.

Early adversity is associated with both internalizing and externalizing problems among children, and effects of adversity on dimensions of child temperament may underlie these links. However, very little is known about the role of child sex in these processes. The current study examined whether there are indirect effects of early adversity on behavior problems through dimensions of child temperament and whether these indirect effects vary across child sex. Participants in this multimethod (parent-report survey, semistructured interview, child protection records) study included 274 preschool-aged children (M[subscript age] = 50.86 months; 52% with documented case of moderate to severe maltreatment) and their primary caregivers assessed at two time points spaced 6 months apart. Results of multigroup path analyses revealed that while anger mediated associations between lifetime stress and behavior problems for the full sample, inhibitory control and appropriate attentional allocation were significant intermediary mechanisms of lifetime stress for boys, but not for girls. Inhibitory control mediated associations between maltreatment and behavior problems for the full sample, but appropriate attentional allocation mediated these associations for boys only. Results suggest that early adversity influences child behavior problems through child temperament, particularly for boys. This work supports the perspective that temperament is influenced by characteristics of the early rearing environment, and the indirect effects of adversity on behavior problems through temperament vary across sex.

Purpose: The landscape of physical education has shifted in the 30 years since Metzler and Freedman's seminal study examining the demographics of physical education teacher education faculty. Changes in the structure of physical education and academia justify an updated investigation, with particular emphasis on the gender and institutional affiliation of faculty. Methods: An expanded and validated version of Metzler and Freedman's survey was e-mailed to 908 physical education teacher education faculty from 505 U.S. institutions. A response rate of 46.21% was achieved. The data were analyzed using descriptive and inferential statistics to examine differences based on gender and institutional affiliation. Results: Gender salary disparities have decreased, whereas teaching experience and qualifications of faculty have increased. Corresponding increases in research productivity were notably evident. Discussion/Conclusion: Faculty members remain predominately European American, publication output has increased, more institutions are hiring nontenure-track faculty, and perceptions of support for physical education are lower than in 1985.

Little is known about the role children's processing of emotions plays in altering children's vulnerability to interparental conflict. To address this gap, the present study examined whether the mediational cascade involving children's exposure to interparental conflict, their insecure responses to interparental conflict, and their psychological problems varied as a function of children's preexisting biases to attend to angry, fearful, sad, and happy expressions. Participants included 243 children (M age = 4.60 years) and their parents assessed at 3 annual measurement occasions. Moderated-mediation analyses within a cross-lagged autoregressive design indicated that the indirect paths among interparental conflict, emotional insecurity, and psychological problems were significant for children who exhibited greater attentional biases toward angry and fearful emotions. Greater attention to anger and fear specifically moderated the first link in the mediational path. Interparental conflict was a significantly stronger predictor of emotional insecurity for children who attended to angry and fearful cues longer. Consistent with environmental sensitivity theories, children with attentional biases to angry and fearful emotions exhibited disproportionately higher levels of emotional insecurity following exposure to heightened interparental conflict but also lower levels of emotional insecurity after experiencing minimal interparental conflict.

In a previous study, we validated the fractions schemes and operations trajectory (Norton and Wilkins 2012; Steffe in J Math Behav 20(3): 267-307, 2002; Steffe and Olive Children's fractional knowledge. Springer, New York, 2010; Wilkins and Norton 2011) with PreK-8 prospective teachers and explored PreK-8 prospective teachers' understanding of fractions based on fraction schemes and operations (Lovin et al. 2016). In that study, we found that most of the prospective teachers had constructed the lower-level fraction schemes and operations, but less than half had constructed the more sophisticated ones. In the current study, we explored ways of evoking the more sophisticated fraction schemes and operations, in particular, by implementing simple instructional changes to a mathematics course for PreK-8 prospective teachers. One change focused on fraction language, specifically encouraging the use of iterative fraction language (e.g., 3/5 is three equal-size pieces, each of which is 1/5 of the whole). Another change focused on intentional number choice, specifically emphasizing improper fractions. After focused fraction instruction that included these instructional changes, we found significant increases in PreK-8 prospective teachers' interiorization of coordinating three levels of units as well as in PreK-8 prospective teachers' construction of the reversible partitive fraction scheme and the iterative fraction scheme. We conclude with implications for practice and research in mathematics courses intended for PreK-8 prospective teachers.

In test-centered standard-setting methods, borderline performance can be represented by many different profiles of strengths and weaknesses. As a result, asking panelists to estimate item or test performance for a hypothetical group study of borderline examinees, or a typical borderline examinee, may be an extremely difficult task and one that can lead to questionable results in setting cut scores. In this study, data collected from a previous standard-setting study are used to deduce panelists' conceptions of profiles of borderline performance. These profiles are then used to predict cut scores on a test of algebra readiness. The results indicate that these profiles can predict a very wide range of cut scores both within and between panelists. Modifications are proposed to existing training procedures for test-centered methods that can account for the variation in borderline profiles.

Anthropometry is important for predicting sports performance. While 3-dimensional (3D) body scanners increase the feasibility of anthropometric assessment, reliability data on athletes are lacking. The aim of this study was to determine the test-retest reliability of a portable, single-camera 3D body scanning system (Styku S100) to assess circumferences, and whole-body and segmental surface areas and volumes of athletes. Forty-nine (19 males) athletes were scanned 6 times (two sessions of three scans). The Styku scanner demonstrated nearly perfect reliability. Systematic errors were negligible (mean standardized bias [95%CI]: scan 1 vs. 4, 0.04 [0.02, 0.06]), random errors were negligible (mean standardized typical error [95%CI]: scan 1 vs. 4, 0.14 [0.10, 0.17]), and test-retest correlations were nearly perfect (mean intra-class correlation coefficient [95%CI]: scan 1 vs. 4, 0.98 [0.97, 0.99]). Single-camera 3D body scanning systems may provide practitioners and researchers with a feasible tool to evaluate body size and shape.

Abstract An integrative taxonomic analysis of Sundaic populations of Gekko smithii from the Thai-Malaya Peninsula, Sumatra, and Borneo recovered four deeply divergent mitochondrial lineages that are separated by major geographic barriers (mountains and seaways). Furthermore, they bear a number of concordant statistically significant differences in meristic and morphometric features, morphospatial separation in multivariate space, and discrete differences in color pattern. Gekko smithii sensu stricto is restricted to southern Thailand south of the Isthmus of Kra and Peninsular Malaysia west of the Banjaran (mountain range) Titiwangsa, being that the type locality is on Penang Island, Penang. Gekko hulk sp. nov. is a new species from extreme southern Thailand and Peninsular Malaysia east of the Banjaran Titiwangsa and five east coast islands—the type locality being Pulau (island) Tioman, Pahang. Gekko cf. albofasciolatus is tentatively used to include Bornean populations west of the Iran Mountains in Sabah and Sarawak which, in the absence of molecular data, cannot unequivocally be separated morphologically from G. albofasciolatus from the type locality at Banjarmasin, Kalimantan, Indonesia east of the Iran Mountains. In the absence of molecular data, G. albomaculatus is resurrected to include mainland Sumatran, Nias Island, and Banyak Islands populations which, based on their morphology, cannot be separated from descriptions of G. albomaculatus from the type locality of Bangka Island, 15 km off the southeast coast of mainland Sumatra. Further integrative analyses of all Sumatran and Bornean populations are currently underway as well as the enigmatic Wallacean populations from Sulawesi. Data are presented that strongly suggest all references to G. smithii from Java stem from a 151 year-old misidentification of a specimen of G. gecko of unknown provenance. Additionally, there are no vouchered records of G. smithii from Myanmar. The phylogeographic patterns of Sundaic populations of the G. smithii complex are concordant with those of a plethora of other Sundaic lineages.

This study re-analyzes morphometric and meristic data among island night lizards, Xantusia riversiana, from the California Channel Islands of San Clemente, Santa Barbara, and San Nicolas in order to ascertain whether the implementation of different statistical methods can recover different results that could potentially alter biological interpretations. Our results concur with a recent previous study demonstrating that the three island populations differ morphologically from one another and that the San Nicolas Island population is the most divergent. Several important aspects, however, of the previous study depart significantly from those recovered here. Our analyses found sexual dimorphism within each population for both morphometric and meristic characters to be relatively uncommon whereas the previous study found nearly all characters to be sexually dimorphic for all island populations. The previous study also recovered significant differences among the three island populations for all morphometric characters whereas far fewer differences were recovered in the present study. Both studies found few significant inter-island differences among the meristic characters. The discordances between these two studies stem from differences in the a priori treatment of the raw character data and the different downstream statistical analyses and visualization techniques used on those data. This was particularly relevant with the use here of an allometric growth algorithm for size-correcting the morphometric data not used in the previous study and by treating all three populations as independently evolving groups. We did not conduct analyses where data from the San Clemente and Santa Barbara island populations were conflated based on their subspecific designation (X. r. reticulata) and then compared to data from the independently evolving San Nicolas Island population. This imprudent use of taxonomy violates the assumptions of statistical independence. We emphasize that explicit justification for the use of particular statistical analyses should occur in all studies—especially if the results bear on the implementation of effective and efficient resource management programs.

Researchers from across the four United States Department of Energy Bioenergy Research Centers (BRCs) engaged in a microbiome workshop that focused on identifying challenges and collaboration opportunities to better understand bioenergy-relevant plant–microbe interactions. The virtual workshop included hands-on educational sessions and a keynote address on current best practices in microbiome science and community microbiome standards, as well as breakout sessions aimed at identifying microbiome-related data and measurements that should be prioritized, opportunities for and barriers to integrating plant metabolites to microbiome research, and strategies for more effectively integrating microbiome data and processes into existing models. Based on participant discussion, key findings of the workshop were the need to prioritize scaling data sharing across BRCs and the broader research community and securing collaborative infrastructure in the areas of microbiome-ecosystem modeling and molecular plant–microbe interactions. This workshop review highlights additional main findings from this event, to encourage cross-site and more holistic metaanalyses while promoting wide scientific community engagement across plant microbiome sciences.

Summary: Cisplatin- and gemcitabine-based chemotherapeutics represent a mainstay of cancer therapy for most solid tumors; however, resistance limits their curative potential. Here, we identify RNA polymerase II-associated factor 1 (PAF1) as a common driver of cisplatin and gemcitabine resistance in human cancers (ovarian, lung, and pancreas). Mechanistically, cisplatin- and gemcitabine-resistant cells show enhanced DNA repair, which is inhibited by PAF1 silencing. We demonstrate an increased interaction of PAF1 with RAD52 in resistant cells. Targeting the PAF1 and RAD52 axis combined with cisplatin or gemcitabine strongly diminishes the survival potential of resistant cells. Overall, this study shows clinical evidence that the expression of PAF1 contributes to chemotherapy resistance and worse clinical outcome for lethal cancers.

Many individuals with spinal cord injury live with debilitating chronic pain that may be neuropathic, nociceptive, or a combination of both in nature. Identification of brain regions demonstrating altered connectivity associated with the type and severity of pain experience may elucidate underlying mechanisms, as well as treatment targets. Resting state and sensorimotor task-based magnetic resonance imaging data were collected in 37 individuals with chronic spinal cord injury. Seed-based correlations were utilized to identify resting state functional connectivity of regions with established roles in pain processing: the primary motor and somatosensory cortices, cingulate, insula, hippocampus, parahippocampal gyri, thalamus, amygdala, caudate, putamen, and periaqueductal gray matter. Resting state functional connectivity alterations and task-based activation associated with individuals’ pain type and intensity ratings on the International Spinal Cord Injury Basic Pain Dataset (0–10 scale) were evaluated. We found that intralimbic and limbostriatal resting state connectivity alterations are uniquely associated with neuropathic pain severity, whereas thalamocortical and thalamolimbic connectivity alterations are associated specifically with nociceptive pain severity. The joint effect and contrast of both pain types were associated with altered limbocortical connectivity. No significant differences in task-based activation were identified. These findings suggest that the experience of pain in individuals with spinal cord injury may be associated with unique alterations in resting state functional connectivity dependent upon pain type.

Elevated lipid panels are associated with an increased risk of cardiovascular disease. Management of heart disease with lipid lowering agents play a vital role in medicine. Statins are one group of medications that are widely utilized in the medical field to decrease the risk of atherosclerotic disease. Statins work by inhibiting the hepatic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Although statins are one of the most effective drugs for secondary and primary prevention of heart disease, they are not without risks and side effects such as hepatotoxicity and myopathy. We present a case of a male patient who developed progressively worsening muscle weakness and elevated muscle enzyme markers upon initiation of a statin. His symptoms persisted despite a trial of an alternative statin and subsequent discontinuation of all statin medications. A multitude of possible etiologies were considered and ranged from infectious, autoimmune, cancerous, to congenital in nature. Environmental factors, such as exposure to medications or toxins, were also considered as one of the possible precipitating factors. The association between his statin consumption and muscle weakness were not easily apparent at first. He required further workup including physical examination, electromyography, panel of myositis antibodies, and muscle biopsy. After clinical suspicion and elevated antibodies to HMGCR beyond the normal limit, he was discovered to have statin-associated autoimmune myopathy. The patient improved with the treatment of immunosuppressive agent’s prednisone and methotrexate.

ABSTRACTPublic participation and engagement in decision-making regarding science and technology (‘PP&E’) is an increasingly common practice. But what is known of whether PP&E achieves its goals? Surprisingly, little research evaluates PP&E. We put forth three reasons why PP&E advocates and practitioners should take evaluation seriously: the absence of evaluation causes PP&E's advocacy to fail a minimal burden-of-proof standard; PP&E's costs are greater than they appear; and these costs may be disproportionately borne by the already-disadvantaged. Evaluating PP&E would require identifying PP&E's objectives and assessing its success in meeting them. To this end we survey scholarship advocating PP&E and identify three sets of objectives: substantively improving decision-making, deontologically fulfilling widely-held norms, and politically redistributing power away from techno-scientific elites. While there is some ad hoc evidence of progress toward these goals, we find no robust evaluation of PP&E. We offer four recommendations that might assist in evaluating PP&E more thoroughly.

HIV and other sexually transmitted infections (STIs) continue to affect men who have sex with men (MSM) and transgender women (TW) in Peru at disproportionately high rates. The ineffectiveness of traditional prevention strategies may be due to the disconnect between health promotion messages and community-level understandings of sexual cultures. We conducted 15 workshops with MSM and TW to develop a community-based sexual health intervention. Intervention development consisted of focus groups and scenic improvisation to identify sexual scripts for an HIV prevention telenovela, or Spanish soap opera. Workshops were stratified by self-reported socioeconomic status, sexual orientation, and gender identity: (1) low-income MSM (n = 9); (2) middle/high-income MSM (n = 6); and (3) TW (n = 8). Employing a conceptual model based on sexual scripts and critical consciousness theories, this paper reports on three themes identified during the telenovela-development process as participants sought to "rescript" social and sexual stereotypes associated with HIV-related vulnerability: (1) management of MSM and TW social identities at the intersection of socioeconomic status, sexuality, and gender performance; (2) social constructions of gender and/or sexual role and perceived and actual HIV/STI risk(s) within sexual partnership interactions; and (3) idealized and actual sexual scripts in the negotiation of safer sex practices between MSM/TW and their partners. These findings are key to reframing existing prevention strategies that fail to effectively engage poorly defined "high-risk populations." Leveraging community-based expertise, the results provide an alternative to the static transfer of information through expert-patient interactions in didactic sessions commonly used in HIV prevention interventions among MSM and TW.

BackgroundGonorrhea (Neisseria gonorrhoeae [GC]) and chlamydia (Chlamydia trachomatis [CT]) disproportionately affect men who have sex with men (MSM), and public health implications vary by anatomic site and bacterial agent. Urethral and rectal GC and CT can increase risk of HIV transmission, whereas pharyngeal GC may be a reservoir for antimicrobial resistance. To define screening priorities in Latin America, we compare differences in the prevalence and correlates of urethral, pharyngeal, and rectal GC and CT among MSM in Peru.MethodsA cross-sectional sample of 787 MSM from Lima was screened between 2012 and 2014. We described prevalence of urethral, pharyngeal, and rectal GC and CT infection and conducted bivariate analyses of associations with social, behavioral, and biological characteristics. Poisson regression analyses assessed the correlates of each infection at each anatomic site.ResultsThe most commonly symptomatic infection (urethral GC; 42.1%) was the least prevalent (2.4%). The most prevalent infections were rectal CT (15.8%) and pharyngeal GC (9.9%). Rectal CT was the least commonly symptomatic (2.4%) infection, and was associated with younger age (adjusted prevalence ratio [95% confidence interval], 0.96 [0.94-0.98]), HIV infection (1.46 [1.06-2.02]), and pasivo (receptive; 3.59 [1.62-7.95]) and moderno (versatile; 2.63 [1.23-5.60]) sexual roles.ConclusionsResults highlight limitations of current syndromic screening strategies for sexually transmitted diseases in Peru, wherein urethral CT and rectal GC and CT may be missed due to their frequently asymptomatic presentations. Successful management of GC and CT infections among MSM in low-resource settings requires differentiating between bacterial agent, symptomatic presentation, associated risk factors, and public health implications of untreated infection at different anatomic sites.

BackgroundGonorrhea (Neisseria gonorrhoeae [GC]) and chlamydia (Chlamydia trachomatis [CT]) disproportionately affect men who have sex with men (MSM), and public health implications vary by anatomic site and bacterial agent. Urethral and rectal GC and CT can increase risk of HIV transmission, whereas pharyngeal GC may be a reservoir for antimicrobial resistance. To define screening priorities in Latin America, we compare differences in the prevalence and correlates of urethral, pharyngeal, and rectal GC and CT among MSM in Peru.MethodsA cross-sectional sample of 787 MSM from Lima was screened between 2012 and 2014. We described prevalence of urethral, pharyngeal, and rectal GC and CT infection and conducted bivariate analyses of associations with social, behavioral, and biological characteristics. Poisson regression analyses assessed the correlates of each infection at each anatomic site.ResultsThe most commonly symptomatic infection (urethral GC; 42.1%) was the least prevalent (2.4%). The most prevalent infections were rectal CT (15.8%) and pharyngeal GC (9.9%). Rectal CT was the least commonly symptomatic (2.4%) infection, and was associated with younger age (adjusted prevalence ratio [95% confidence interval], 0.96 [0.94-0.98]), HIV infection (1.46 [1.06-2.02]), and pasivo (receptive; 3.59 [1.62-7.95]) and moderno (versatile; 2.63 [1.23-5.60]) sexual roles.ConclusionsResults highlight limitations of current syndromic screening strategies for sexually transmitted diseases in Peru, wherein urethral CT and rectal GC and CT may be missed due to their frequently asymptomatic presentations. Successful management of GC and CT infections among MSM in low-resource settings requires differentiating between bacterial agent, symptomatic presentation, associated risk factors, and public health implications of untreated infection at different anatomic sites.

BackgroundObesity rates are increasing among HIV-infected individuals, but risk factors for obesity development on ART remain unclear.ObjectivesIn a cohort of HIV-infected adults in Rio de Janeiro, Brazil, we aimed to determine obesity rates before and after ART initiation and to analyse risk factors for obesity on ART.MethodsWe retrospectively analysed data from individuals initiating ART between 2000 and 2015. BMI was calculated at baseline (time of ART initiation). Participants who were non-obese at baseline and had ≥90 days of ART exposure were followed until the development of obesity or the end of follow-up. Obesity incidence rates were estimated using Poisson regression models and risk factors were assessed using Cox regression models.ResultsOf participants analysed at baseline (n = 1794), 61.3% were male, 48.3% were white and 7.9% were obese. Among participants followed longitudinally (n = 1567), 66.2% primarily used an NNRTI, 32.9% a PI and 0.9% an integrase strand transfer inhibitor (INSTI); 18.3% developed obesity and obesity incidence was 37.4 per 1000 person-years. In multivariable analysis, the greatest risk factor for developing obesity was the use of an INSTI as the primary ART core drug (adjusted HR 7.12, P

BackgroundPatient-initiated partner notification (PN) following the diagnosis of a sexually transmitted infection is a critical component of disease control in men who have sex with men (MSM) sexual networks. Both printed and internet-based technologies offer potential tools to enhance traditional partner notification approaches among MSM in resource-limited settings.ObjectiveThis randomized controlled trial aimed to evaluate the effect of 2 different PN technologies on notification outcomes following syphilis diagnosis among MSM in Peru: a Web-based notification system and patient-delivered partner referral cards.MethodsDuring 2012-2014, we screened 1625 MSM from Lima, Peru, for syphilis infection and enrolled 370 MSM with symptomatic primary or secondary syphilis (n=58) or asymptomatic latent syphilis diagnosed by serology (rapid plasma reagin, RPR, and Microhemagglutination assay for Treponema pallidum antibody; n=312). Prior to enrollment, potential participants used a computer-based self-interviewing system to enumerate their recent sexual partnerships and provide details of their 3 most recent partners. Eligible participants were randomly assigned to one of 4 intervention arms: (1) counseling and patient-initiated Web-based PN (n=95), (2) counseling with Web-based partner notification and partner referral cards (n=84), (3) counseling and partner referral cards (n=97), and (4) simple partner notification counseling (control; n=94). Self-reported partner notification was assessed after 14 days among 354 participants who returned for the follow-up assessment.ResultsThe median age of enrolled participants was 27 (interquartile range, IQR 23-34) years, with a median of 2 partners (IQR 1-5) reported in the past month. Compared with those who received only counseling (arm 4), MSM provided with access to Web-based partner notification (arms 1 and 2) or printed partner referral cards (arms 2 and 3) were more likely to have notified one or more of their sexual partners (odds ratio, OR, 2.18, 95% CI 1.30-3.66; P=.003 and OR 1.68, 95% CI 1.01-2.79; P=.045, respectively). The proportion of partners notified was also higher in both Web-based partner notification (241/421, 57.2%; P

Medical errors are a leading cause of morbidity and mortality in the medical field and are substantial contributors to medical costs. Radiologists play an integral role in the diagnosis and care of patients and, given that those in this field interpret millions of examinations annually, may therefore contribute to diagnostic errors. Errors can be categorized as a "miss" when a primary or critical finding is not observed or as a "misinterpretation" when errors in interpretation lead to an incorrect diagnosis. In this article, the authors describe the cognitive causes of such errors in diagnostic medicine, specifically in radiology. Recognizing the cognitive processes that radiologists use while interpreting images should improve one's awareness of the inherent biases that can impact decision making. The authors review the common biases that impact clinical decisions, as well as strategies to counteract or minimize the potential for misdiagnosis. System-level processes that can be implemented to minimize cognitive errors are reviewed, as well as ways to implement personal changes to minimize cognitive errors in daily practice. ©RSNA, 2017.

Abstract Bio-inspired Topographically Mediated Surfaces (TMSs) based on high aspect ratio nanostructures have recently been attracting significant attention due to their pronounced antimicrobial properties by mechanically disrupting cellular processes. However, scalability of such surfaces is often greatly limited, as most of them rely on micro/nanoscale fabrication techniques. In this report, a cost-effective, scalable, and versatile approach of utilizing diamond nanotechnology for producing TMSs, and using them for limiting the spread of emerging infectious diseases, is introduced. Specifically, diamond-based nanostructured coatings are synthesized in a single-step fabrication process with a densely packed, needle- or spike-like morphology. The antimicrobial proprieties of the diamond nanospike surface are qualitatively and quantitatively analyzed and compared to other surfaces including copper, silicon, and even other diamond surfaces without the nanostructuring. This surface is found to have superior biocidal activity, which is confirmed via scanning electron microscopy images showing definite and widespread destruction of E. coli cells on the diamond nanospike surface. Consistent antimicrobial behavior is also observed on a sample prepared seven years prior to testing date. Graphical Abstract

ABSTRACT Lipo-chitooligosaccharides (LCOs) are historically known for their role as microbial-derived signaling molecules that shape plant symbiosis with beneficial rhizobia or mycorrhizal fungi. Recent studies showing that LCOs are widespread across the fungal kingdom have raised questions about the ecological function of these compounds in organisms that do not form symbiotic relationships with plants. To elucidate the ecological function of these compounds, we investigate the metabolomic response of the ubiquitous human pathogen Aspergillus fumigatus to LCOs. Our metabolomics data revealed that exogenous application of various types of LCOs to A. fumigatus resulted in significant shifts in the fungal metabolic profile, with marked changes in the production of specialized metabolites known to mediate ecological interactions. Using network analyses, we identify specific types of LCOs with the most significant effect on the abundance of known metabolites. Extracts of several LCO-induced metabolic profiles significantly impact the growth rates of diverse bacterial species. These findings suggest that LCOs may play an important role in the competitive dynamics of non-plant-symbiotic fungi and bacteria. This study identifies specific metabolomic profiles induced by these ubiquitously produced chemicals and creates a foundation for future studies into the potential roles of LCOs as modulators of interkingdom competition. IMPORTANCE The activation of silent biosynthetic gene clusters (BGC) for the identification and characterization of novel fungal secondary metabolites is a perpetual motion in natural product discoveries. Here, we demonstrated that one of the best-studied symbiosis signaling compounds, lipo-chitooligosaccharides (LCOs), play a role in activating some of these BGCs, resulting in the production of known, putative, and unknown metabolites with biological activities. This collection of metabolites induced by LCOs differentially modulate bacterial growth, while the LCO standards do not convey the same effect. These findings create a paradigm shift showing that LCOs have a more prominent role outside of host recognition of symbiotic microbes. Importantly, our work demonstrates that fungi use LCOs to produce a variety of metabolites with biological activity, which can be a potential source of bio-stimulants, pesticides, or pharmaceuticals.

Transgender women (TW) represent a vulnerable population at increased risk for HIV infection in Peru. A mixed-methods study with 48 TW and 19 healthcare professionals was conducted between January and February 2015 to explore barriers and facilitators to implementing a model of care that integrates HIV services with gender-affirmative medical care (i.e., hormone therapy) in Lima, Peru. Perceived acceptability of the integrated care model was high among TW and healthcare professionals alike. Barriers included stigma, lack of provider training or Peruvian guidelines regarding optimal TW care, and service delivery obstacles (e.g., legal documents, spatial placement of clinics, hours of operation). The hiring of TW staff was identified as a key facilitator for engagement in health care. Working in partnership with local TW and healthcare provider organizations is critical to overcoming existing barriers to successful implementation of an integrated HIV services and gender-affirmative medical care model for this key population in Peru.

BackgroundSyphilis infection has recently resurfaced as a significant public health problem. Although there has been a tremendous amount of research on the epidemiology of syphilis, there has been limited work done to synthesize the extensive body of research and systematically estimate patterns of disease within high-risk groups in the Americas. The purpose of this systematic review and meta-analysis is to (1) summarize recent patterns of syphilis infection in North and South America among four high-risk groups (MSM, transgender women, sex workers, and incarcerated individuals) from 1980 to 2016, (2) identify and differentiate regional geographic epidemiologic characteristics, and (3) compare the epidemics of the economically developed countries of North America from the developing countries and public health systems of Latin America and the Caribbean.Methods/designPrimary studies reporting syphilis prevalence and/or incidence in at least one of the four high-risk groups will be identified from Medline/PubMed, Embase, Lilacs, SciELO, The Cochrane Library, Web of Science, Scopus, ProQuest, CINAHL, Clase, and Periódica, as well as "gray" literature sources (conference abstracts, country reports, etc.). Studies published from 1980 through 2016 will be included. Data will be extracted from studies meeting inclusion and exclusion criteria and a random effects meta-analysis of prevalence and incidence estimates will be conducted. Heterogeneity, risk of bias, and publication bias will be assessed. Pooled prevalence and incidence estimates will be calculated for comparisons based on geographic region, risk factors, and time period.DiscussionOur systematic review and meta-analysis aims to contribute to an improved understanding of global epidemiologic patterns of syphilis infection in most-at-risk populations. Through systematic classification of the existing literature, and comparison of disease patterns across regional, temporal and socio-behavioral differences, we hope to improve public health surveillance and improve efforts to control the spread of disease across the Americas.Systematic review registrationPROSPERO CRD42016047306.

BackgroundExpedited Partner Therapy (EPT) has been shown to improve treatment outcomes among heterosexual partners of individuals with curable sexually transmitted infections (STIs). Although the use of EPT with men who have sex with men (MSM) has been debated, due to the potential for missed opportunities to diagnose unidentified cases of HIV and syphilis infection in symptomatic partners, increases in partner notification (PN) resulting from use of EPT may promote testing and treatment of otherwise unidentified partners. We assessed the impact of EPT on self-reported PN among MSM in Peru with gonorrheal (GC) and/or chlamydial (CT) infection.MethodsWe enrolled 173 MSM in Lima, Peru with symptomatic or asymptomatic GC and/or CT infection between 2012 and 2014. We enrolled 44 MSM with symptomatic urethritis/proctitis and 129 MSM with asymptomatic GC/CT infection, diagnosed based on nucleic acid testing (Aptima Combo 2 Transcription-Mediated Amplification [TMA]) from urethral, pharyngeal, and rectal sites. Eligible participants were randomly assigned to receive either standard PN counseling (n = 84) or counseling plus EPT (cefixime 400 mg/azithromycin 1 g) for up to five recent partners (n = 89). Self-reported notification was assessed by computer-assisted self-administered survey among 155 participants who returned for 14-day follow-up.ResultsThe median age of participants was 26 (interquartile range [IQR]: 23-31) with a median of 3 sexual partners (IQR: 2-4) in the previous 30-day period. Among all participants, 111/155 (71.6%) notified at least one partner at 14-day follow-up with a median of 1 partner notified per participant (IQR: 0-2). For participants randomized to receive EPT, 69/83 (83.1%) reported notifying at least one partner, compared with 42/72 (58.3%) of participants in the control arm (odds ratio = 3.52; 95% confidence interval [CI]: 1.68-7.39). The proportion of all recent partners notified was significantly greater in the EPT than in the control arm (53.5%, 95% CI: 45.0-62.0% versus 36.4%, 95% CI: 27.0-47.4%).ConclusionsProvision of EPT led to significant increases in notification among Peruvian MSM diagnosed with GC/CT infection. Additional research is needed to assess the impact of EPT on biological outcomes, including persistent or recurrent infection, antimicrobial resistance, and HIV/STI transmission, in MSM sexual networks.Trial registrationClinicalTrials.gov, NCT01720654 . Registered on 10/29/2012.