Cefiderocol-Based Regimen for Acinetobacter NDM-1 Outbreak.

Variable outcomes have been reported with cefiderocol in infections due to carbapenem-resistant Acinetobacter baumannii (CRAB). Nonetheless, it may be the only option for metallo-beta-lactamase-producing strains. We describe an outbreak of NDM-CRAB infections treated with cefiderocol. Thirty-eight patients were colonized and/or infected. Thirteen patients developed a systemic infection. A clinical cure was achieved in 10 (83%) patients, one VAP and 9 BSIs, at day 7. In vitro, the activity of cefiderocol does not appear to match in vivo effectiveness using currently available commercial tests. Despite high clinical cures, overall mortality remains high in severely ill patients. Cefiderocol may be considered in this specific setting, though the implementation of susceptibility tests and infection control measures is mandatory.

MYC is a clinically significant driver of mTOR inhibitor resistance in breast cancer.

Targeting the PI3K-AKT-mTOR pathway is a promising therapeutic strategy for breast cancer treatment. However, low response rates and development of resistance to PI3K-AKT-mTOR inhibitors remain major clinical challenges. Here, we show that MYC activation drives resistance to mTOR inhibitors (mTORi) in breast cancer. Multiomic profiling of mouse invasive lobular carcinoma (ILC) tumors revealed recurrent Myc amplifications in tumors that acquired resistance to the mTORi AZD8055. MYC activation was associated with biological processes linked to mTORi response and counteracted mTORi-induced translation inhibition by promoting translation of ribosomal proteins. In vitro and in vivo induction of MYC conferred mTORi resistance in mouse and human breast cancer models. Conversely, AZD8055-resistant ILC cells depended on MYC, as demonstrated by the synergistic effects of mTORi and MYCi combination treatment. Notably, MYC status was significantly associated with poor response to everolimus therapy in metastatic breast cancer patients. Thus, MYC is a clinically relevant driver of mTORi resistance that may stratify breast cancer patients for mTOR-targeted therapies.

CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer.

Cancer-associated fibroblasts (CAFs) are abundantly present in the microenvironment of virtually all tumors and strongly impact tumor progression. Despite increasing insight into their function and heterogeneity, little is known regarding the origin of CAFs. Understanding the origin of CAF heterogeneity is needed to develop successful CAF-based targeted therapies. Through various transplantation studies in mice, we show that CAFs in both invasive lobular breast cancer and triple-negative breast cancer originate from mammary tissue-resident normal fibroblasts (NFs). Single-cell transcriptomics, in vivo and in vitro studies reveal the transition of CD26+ and CD26- NF populations into inflammatory CAFs (iCAFs) and myofibroblastic CAFs (myCAFs), respectively. Functional co-culture experiments show that CD26+ NFs transition into pro-tumorigenic iCAFs which recruit myeloid cells in a CXCL12-dependent manner and enhance tumor cell invasion via matrix-metalloproteinase (MMP) activity. Together, our data suggest that CD26+ and CD26- NFs transform into distinct CAF subpopulations in mouse models of breast cancer.

Comparing forces on the fetal neck in breech delivery in lithotomy versus all-fours position: a simulation model.

PURPOSE: To measure forces applied to the fetal neck, in a simulation model for breech delivery, in both lithotomy versus all-fours position. METHODS: We used a Laerdal SimMom simulator and a Birthing Baby together with PROMPT Flex Software. The descent of the fetus was accomplished using the Automatic Delivery Module 2. The baby was always in breech position; the SimMom in either all-fours or lithotomy positions. Sensors were located inside the fetal neck region to simulate forces applied to the plexus. RESULTS: The lowest force on the fetal neck region was recorded for the delivery in all-fours position without further maneuvers (mean force 58.70 Newton, standard deviation 2.54 N). As weight was added to the baby, the force increased (i.e. + 500 g, mean force 71.8 N, SD 3.08 N, p < 0.001). Delivery in lithotomy position resulted in a mean force of 81.56 N (SD 19.55 N). The force significantly increased in case of delivery of the head without assistance from contractions (mean force 127.93 N, SD 23.10 N). In all-fours position, the delivery of the fetal head from pelvic floor level without contractions (Frank's Nudge maneuver) resulted in a mean force of 118.45 N (SD 15.48 N, p = 0.02). Maneuvers for shoulder dystocia (the inverted type that can occur during breech delivery) led to significantly higher mean forces independent from birthing positions. CONCLUSION: Breech delivery in all-fours position was associated with the lowest force acting on the fetal neck in our simulation model.

MYC promotes immune-suppression in triple-negative breast cancer via inhibition of interferon signaling.

The limited efficacy of immune checkpoint inhibitor treatment in triple-negative breast cancer (TNBC) patients is attributed to sparse or unresponsive tumor-infiltrating lymphocytes, but the mechanisms that lead to a therapy resistant tumor immune microenvironment are incompletely known. Here we show a strong correlation between MYC expression and loss of immune signatures in human TNBC. In mouse models of TNBC proficient or deficient of breast cancer type 1 susceptibility gene (BRCA1), MYC overexpression dramatically decreases lymphocyte infiltration in tumors, along with immune signature remodelling. MYC-mediated suppression of inflammatory signalling induced by BRCA1/2 inactivation is confirmed in human TNBC cell lines. Moreover, MYC overexpression prevents the recruitment and activation of lymphocytes in both human and mouse TNBC co-culture models. Chromatin-immunoprecipitation-sequencing reveals that MYC, together with its co-repressor MIZ1, directly binds promoters of multiple interferon-signalling genes, resulting in their downregulation. MYC overexpression thus counters tumor growth inhibition by a Stimulator of Interferon Genes (STING) agonist via suppressing induction of interferon signalling. Together, our data reveal that MYC suppresses innate immunity and facilitates tumor immune escape, explaining the poor immunogenicity of MYC-overexpressing TNBCs.

HIV incidence, viremia, and the national response in Eswatini: Two sequential population-based surveys.

With the highest HIV incidence and prevalence globally, the government of Eswatini started a substantial scale-up of HIV treatment and prevention services in 2011. Two sequential large population-based surveys were conducted before and after service expansion to assess the impact of the national response. Cross-sectional, household-based, nationally representative samples of adults, ages 18 to 49 years, were sampled in 2011 and 2016. We measured HIV prevalence, incidence (recent infection based on limiting antigen ≤1.5 optical density units and HIV RNA ≥1000 copies/mL), viral load suppression (HIV RNA <1000 copies/mL among all seropositive adults) and unsuppressed viremia (HIV RNA ≥1000 copies/mL among all, regardless of HIV status) and assessed for temporal changes by conducting a trend analysis of the log ratio of proportions, using a Z statistic distribution. HIV prevalence remained stable from 2011 to 2016 [32% versus 30%, p = 0.10]. HIV incidence significantly declined 48% [2.48% versus 1.30%, p = 0.01]. Incidence remained higher among women than men [2011: 3.16% versus 1.83%; 2016: 1.76% versus 0.86%], with a smaller but significant relative reduction among women [44%; p = 0.04] than men [53%; p = 0.09]. The proportion of seropositive adults with viral load suppression significantly increased from 35% to 71% [p < .001]. The proportion of the total adult population with unsuppressed viremia decreased from 21% to 9% [p < .001]. National HIV incidence in Eswatini decreased by nearly half and viral load suppression doubled over a five-year period. Unsuppressed viremia in the total population decreased 58%. These population-based findings demonstrate the national impact of expanded HIV services in a hyperendemic country.

Self-Rated Health Among Patients With Severe Traumatic Brain Injury and Their Close Relatives: The Role of Posttraumatic Stress Symptoms.

OBJECTIVE: Severe traumatic brain injury (sTBI) is accompanied by significant declines in self-rated health (SRH). Although such deteriorations in SRH are related to various consequences of sTBI, the effect of posttraumatic reactions (i.e., posttraumatic stress [PTS] symptoms) has been tested insufficiently to date, especially among civilians. The present investigation is based on Trajectories of Recovery After Severe Traumatic brain injury-Matters In families (TRAST-MI), a unique study among civilians with sTBI and their families. Previous research revealed that civilian sTBI has effects beyond the injured patient, influencing their close relatives as well. The aim of this study was to assess the association between PTS symptoms and SRH among patients with civilian sTBI and their close relatives. METHODS: Patients with sTBI (assessed by an Abbreviated Injury Scale of the head region score >3) and their close relatives participated in TRAST-MI. One hundred twenty-six patient-relative dyads were assessed at 3, 6, and 12 months after the injury. RESULTS: Multilevel modeling revealed that patients' PTS symptoms were associated with consequent SRH (slope = 0.42; p < .001), and relatives' PTS symptoms were associated with their respective SRH (slope = 0.2; p = .012). CONCLUSIONS: The findings of this study reveal that SRH of both patients with sTBI and their relatives are negatively affected by their own PTS symptoms. These findings underline the understanding that sTBI is not merely a medical trauma but rather a comprehensive psychosocial trauma, which has consequences for the whole family system.

Exploration of Ligand-receptor Binding and Mechanisms for Alginate Reduction and Phenotype Reversion by Mucoid Pseudomonas aeruginosa.

Bacteria in general can develop a wide range of phenotypes under different conditions and external stresses. The phenotypes that reside in biofilms, overproduce exopolymers, and show increased motility often exhibit drug tolerance and drug persistence. In this work, we describe a class of small molecules that delay and inhibit the overproduction of alginate by a non-swarming mucoid Pseudomonas aeruginosa. Among these molecules, selected benzophenone-derived alkyl disaccharides cause the mucoid bacteria to swarm on hydrated soft agar gel and revert the mucoid to a nonmucoid phenotype. The sessile (biofilm) and motile (swarming) phenotypes are controlled by opposing signaling pathways with high and low intracellular levels of bis-(3',5')-cyclic diguanosine monophosphate (cdG), respectively. As our molecules control several of these phenotypes, we explored a protein receptor, pilin of the pili appendages, that is consistent with controlling these bioactivities and signaling pathways. To test this binding hypothesis, we developed a bacterial motility-enabled binding assay that uses the interfacial properties of hydrated gels and bacterial motility to conduct label-free ligand-receptor binding studies. The structure-activity correlation and receptor identification reveal a plausible mechanism for reverting mucoid to nonmucoid phenotypes by binding pili appendages with ligands capable of sequestering and neutralizing reactive oxygen species.

The Pre-Exposure Prophylaxis Cascade in At-Risk Transgender Men Who Have Sex with Men in the United States.

Purpose: This analysis was designed to characterize the pre-exposure prophylaxis (PrEP) cascade in a U.S. national sample of transgender men and trans masculine adults who have sex with cisgender men (trans MSM) at-risk for HIV acquisition. Methods: From November to December 2017, 843 HIV-negative trans MSM self-reporting past-6-month receptive sex with a cisgender man were recruited via peer referrals, dating apps, listservs, and social media. A computer-assisted self-interview assessed demographics, health care, and the PrEP cascade. Descriptive statistics and multivariable regression models evaluated factors associated with PrEP uptake and persistence. Results: Mean age was 28.1 years (standard deviation = 7.1); 4.8% were Black, 21.7% Latinx, and 25.6% another race/ethnicity. A total of 84.1% had heard of PrEP, with 67.3% reporting interest. More than half (55.2%) were PrEP indicated, of which 50.8% were PrEP naive. Approximately 1/4 (28.0%) reported PrEP use, of which 65.3% were PrEP persistent. PrEP modality preferences were injectable (51.2%), daily oral pill (22.1%), and anal gel/lube (14.6%). Reasons for PrEP noninterest were no HIV risk (68.5%), cost (24.2%), and side effects (20.1%). Surgical gender affirmation, no health care discrimination, and social media as a primary health information source were associated with increased odds of PrEP uptake and persistence (all p < 0.05). PrEP adherence difficulties were reported by 52.6%, due to busy/inconsistent schedule (53.1%), side effects (27.4%), and too many medical visits (11.6%). Conclusion: PrEP uptake was modest among the trans MSM sampled, given prevalent HIV risk behaviors. The limited PrEP uptake in at-risk trans MSM suggests the need to develop culturally tailored community education and interventions.

The effect of mindful attention training for pain modulation capacity: Exploring the mindfulness-pain link.

OBJECTIVE: Mindfulness has been shown to be beneficial for chronic pain. The underlying mechanisms of the mindfulness-pain link, however, are yet to be established. Particularly, the effects of mindfulness on pain modulation, which is shown to be dysfunctional among chronic pain patients, barely has been tested. This study investigated whether a short mindful attention training based on Langerian mindfulness mitigates reductions in pain modulation. METHOD: Systemic quantitative-somatosensory testing of conditioned pain modulation (CPM) was conducted in 60 undergraduates, who were randomly assigned to one of three groups: (1) Pain-specific mindful attention training; (2) nonspecific mindful attention training; and (3) no mindful attention training. CPM was tested before and after the intervention. RESULTS: As hypothesized, a reduction in CPM magnitude was observed only in the control group, whereas this reduction was abolished in the two mindfulness groups. CONCLUSIONS: Langerian mindfulness may mitigate pain modulation reduction as observed in chronic pain, thus shedding light on its potential advantages.

Galectin-3 in Prostate Cancer Stem-Like Cells Is Immunosuppressive and Drives Early Metastasis.

Galectin-3 (Gal-3) is an extracellular matrix glycan-binding protein with several immunosuppressive and pro-tumor functions. The role of Galectin-3 in cancer stem-like cells (CSCs) is poorly investigated. Here, we show that prostate CSCs also colonizing prostate-draining lymph nodes of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice overexpress Gal-3. Gal-3 contributes to prostate CSC-mediated immune suppression because either Gal-3 silencing in CSCs, or co-culture of CSCs and T cells in the presence of the Gal-3 inhibitor N-Acetyl-D-lactosamine rescued T cell proliferation. N-Acetyl-D-lactosamine also rescued the proliferation of T cells in prostate-draining lymph nodes of TRAMP mice affected by prostate intraepithelial neoplasia. Additionally, Gal-3 impacted prostate CSC tumorigenic and metastatic potential in vivo, as Gal-3 silencing in prostate CSCs reduced both primary tumor growth and secondary invasion. Gal-3 was also found expressed in more differentiated prostate cancer cells, but with different intracellular distribution as compared to CSCs, which suggests different functions of Gal-3 in the two cell populations. In fact, the prevalent nuclear and cytoplasmic distribution of Gal-3 in prostate CSCs made them less susceptible to apoptosis, when compared to more differentiated prostate cancer cells, in which Gal-3 was predominantly intra-cytoplasmic. Finally, we found Gal-3 expressed in human and mouse prostate intraepithelial neoplasia lesions and in metastatic lymph nodes. All together, these findings identify Gal-3 as a key molecule and a potential therapeutic target already in the early phases of prostate cancer progression and metastasis.

Decision-Making And Selection Bias in Four Observational Studies on Duchenne and Becker Muscular Dystrophy.

BACKGROUND: Natural history data are essential for trial design in Duchenne (DMD) and Becker muscular dystrophy (BMD), but recruitment for observational studies can be challenging. OBJECTIVE: We reviewed reasons why patients or caregivers declined participation, and compared characteristics of participants and non-participants to assess possible selection bias in four observational studies, three on DMD and one on BMD. METHODS: Three pediatric DMD studies focused on cross-sectional cognitive function and brain MRI (DMDbrain, n = 35 and DMDperfusion, n = 12), and on longitudinal upper extremity function and muscle MRI (DMDarm, n = 22). One adult BMD study assessed longitudinal functioning (n = 36). Considerations for non-participation were retrospectively reviewed from screening logs. Age, travel-time, DMD gene mutations and age at loss of ambulation (DMDarm and BMD study only), of participants and non-participants were derived from the Dutch Dystrophinopathy Database and compared using nonparametric tests (p < 0.05). RESULTS: The perceived burden of the protocol (38.2%), use of MRI (30.4%), and travel-time to the study site (19.1%) were the most frequently reported considerations for non-participation. Only few patients reported lack of personal gain (0.0- 5.9%). Overall, participating patients were representative for the studied sub-populations, except for a younger age of DMDarm study participants and a complete lack of participants with a mutation beyond exon 63. CONCLUSION: Optimizing patient involvement in protocol design, improving MRI experiences, and integrating research into clinics are important factors to decrease burden and facilitate participation. Nationwide registries are essential to compare participants and non-participants and ensure representative observational research. Specific effort is needed to include patients with distal mutations in cognitive studies.

Identification of Substance-Exposed Newborns and Neonatal Abstinence Syndrome Using ICD-10-CM - 15 Hospitals, Massachusetts, 2017.

Opioid use disorder and neonatal abstinence syndrome (NAS) increased in Massachusetts from 1999 to 2013 (1,2). In response, in 2016, the state passed a law requiring birth hospitals to report the number of newborns who were exposed to controlled substances to the Massachusetts Department of Public Health (MDPH)* by mandating monthly reporting of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes related to maternal dependence on opioids (F11.20) or benzodiazepines (F13.20) and to newborns affected by maternal use of drugs of addiction (P04.49) or experiencing withdrawal symptoms from maternal drugs of addiction (P96.1) separately.† MDPH uses these same codes for monthly, real-time crude estimates of NAS and uses P96.1 alone for official NAS state reporting.§ MDPH requested CDC's assistance in evaluating the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of either maternal or newborn codes to identify substance-exposed newborns, and of newborn exposure codes (both exposure [P04.49] or withdrawal [P96.1]) and the newborn code for withdrawal alone (P96.1) to identify infants with NAS cases related to three exposure scenarios: 1) opioids, 2) opioids or benzodiazepines, and 3) any controlled substance. Confirmed diagnoses of substance exposure and NAS abstracted from linked clinical records for 1,123 infants born in 2017 and their birth mothers were considered the diagnostic standard and were compared against hospital-reported ICD-10-CM codes. For identifying substance-exposed newborns across the three exposure scenarios, the newborn exposure codes had higher sensitivity (range = 31%-61%) than did maternal drug dependence codes (range = 16%-41%), but both sets of codes had high PPV (≥74%). For identifying NAS, for all exposure scenarios, the sensitivity for either newborn code (P04.49 or P96.1) was ≥92% and the PPV was ≥64%; for P96.1 alone the sensitivity was ≥79% and the PPV was ≥92% for all scenarios. Whereas ICD-10-CM codes are effective for NAS surveillance in Massachusetts, they should be applied cautiously for substance-exposed newborn surveillance. Surveillance for substance-exposed newborns using ICD-10-CM codes might be improved by increasing the use of validated substance-use screening tools and standardized facility protocols and improving communication between patients and maternal health and infant health care providers.

Patients' recovery after severe TBI is associated with their close relatives' interpersonal functioning: a 12-months prospective cohort study.

OBJECTIVE: The aim of this study was to investigate the association between relatives' interpersonal functioning and patients' recovery after severe traumatic brain injury (TBI) across one year in Switzerland. Design: This prospective, multi-center cohort study is comprised of 188 adult patients with severe TBI (Abbreviated Head Injury Score > 3) and their relatives. Patients and relatives were assessed 3, 6, and 12 months post-injury. Main outcome measures: Interpersonal functioning (Patient Competency Rating Scale for Neurorehabilitation, PCRS-NR), Physical and Mental Health related Quality of Life (HRQoL, SF-12), and overall functioning (Glasgow Outcome Comma Scale Extended, GOSE). Results: Multilevel analyses showed that relatives' interpersonal functioning was positively associated with a) patients' mental HRQoL (p =.002; slope = 2.95; ß =.24) independently of age, b) a moderation time*patients' physical HRQoL among patients > 50 years of age (p <.045; slope = 2.63; ß =.2) and c) patients' GOSE among younger individuals (p <.001; slope =.60; ß =.23). Conclusion: These findings show that health and overall functioning are linked with interpersonal dimensions. Thus, the interplay between relatives and patients with TBI needs to be further investigated.

Long-term data with idebenone on respiratory function outcomes in patients with Duchenne muscular dystrophy.

Decline in respiratory function in patients with DMD starts during early teenage years and leads to early morbidity and mortality. Published evidence of efficacy for idebenone on respiratory function outcomes is currently limited to 12 months of follow-up time. Here we report data collected as retrospective cohort study (SYROS) from 18 DMD patients not using glucocorticoids who were treated with idebenone (900 mg/day) under Expanded Access Programs (EAPs). The objective was to assess the long-term respiratory function evolution for periods On-Idebenone compared to periods Off-Idebenone in the same patients. The mean idebenone exposure in the EAPs was 4.2 (range 2.4-6.1) years. The primary endpoint was the annual change in forced vital capacity percent of predicted (FVC%p) compared between Off-Idebenone and On-Idebenone periods. The annual rate of decline in FVC%p was reduced by approximately 50% from -7.4% (95% CI: -9.1, -5.8) for the Off-Idebenone periods to -3.8% (95% CI: -4.8, -2.8) for the On-Idebenone periods (N = 11). Similarly, annual change in peak expiratory flow percent of predicted (PEF%p) was -5.9% (95% CI: -8.0, -3.9) for the Off-Idebenone periods (N = 9) and reduced to -1.9% (95% CI: -3.2, -0.7) for the On-Idebenone periods during the EAPs. The reduced rates of decline in FVC%p and PEF%p were maintained for several years with possible beneficial effects on the rate of bronchopulmonary adverse events, time to 10% decline in FVC%p and risk of hospitalization due to respiratory cause. These long-term data provide Class IV evidence to further support the disease modifying treatment effect of idebenone previously observed in randomized, controlled trials.

Gender Non-affirmation from Cisgender Male Partners: Development and Validation of a Brief Stigma Scale for HIV Research with Transgender Men Who Have Sex with Men (Trans MSM).

Some transgender men who have sex with men (trans MSM) are vulnerable to HIV infection and face stigma from sexual partners. We evaluated a brief 4-item measure of gender non-affirmation from cisgender male partners. A non-probability sample of American trans MSM (n = 843) reporting past 6-month sexual contact with a cisgender male completed a cross-sectional survey. Psychometric analyses assessed the scale and modeled HIV risk associations. Overall, 78% experienced past 6-month gender non-affirmation from cisgender male partners. The scale demonstrated good reliability (α = 0.78). Convergent validity was supported in associations with psychological distress and anxiety (p < 0.05). Lower frequency of cisgender male partner stigma was associated with increased odds of past 6-month HIV testing and decreased odds of past 6-month condomless receptive sex (all p < 0.01). The gender non-affirmation from cisgender male sexual partners scale found negative associations with protective health behaviors and can be used to better understand the context of trans MSM risk behavior.

Cell-Wall-Targeting Antibiotics Cause Lag-Phase Bacteria to Form Surface-Mediated Filaments Promoting the Formation of Biofilms and Aggregates.

Antibiotics are known to promote bacterial formation of enhanced biofilms, the mechanism of which is not well understood. Here, using biolayer interferometry, we have shown that bacterial cultures containing antibiotics that target cell walls cause biomass deposition on surfaces over time with a linear profile rather than the Langmuir-like profiles exhibited by bacterial adherence in the absence of antibiotics. We observed about three times the initial rate and 12 times the final biomass deposition on surfaces for cultures containing carbenicillin than without. Unexpectedly, in the presence of antibiotics, the rate of biomass deposition inversely correlated with bacterial densities from different stages of a culture. Detailed studies revealed that carbenicillin caused faster growth of filaments that were seeded on surfaces from young bacteria (from lag phase) than those from high-density fast-growing bacteria, with rates of filament elongation of about 0.58 and 0.13 µm min-1 , respectively. With surfaces that do not support bacterial adherence, few filaments were observed even in solution. These filaments aggregated in solution and formed increased amounts of biofilms on surfaces. These results reveal the lifestyle of antibiotic-induced filamentous bacteria, as well as one way in which the antibiotics promote biofilm formation.

Physical and Mental Health and Functioning Among Traumatic Brain Injury Close Relatives: The Role of Posttraumatic Stress Symptoms.

Severe Traumatic brain injury (sTBI) often instigates widespread long-lasting disability and is accompanied by extensive rehabilitation. Unsurprisingly, sTBI also holds malignant consequences for patients' close relatives. The burden caused by the injury and its severity explains some of the ramifications for the relatives. Additionally, some findings demonstrate that patients with sTBI and their relatives develop posttraumatic stress (PTS) symptoms. However, although the link between PTS symptoms and physical and mental health is well-documented in literature, the effect of PTS symptoms on relatives of patients with sTBI has barely been examined. This study examines the influence of PTS symptoms of patients with sTBI and their relatives on the physical and mental health and functioning of the relatives. Patients who sustained a severe sTBI (Abbreviated Injury Scale of the head region > 3) and close relatives were included in a multi-center, prospective cohort study (TRAST-MI). One-hundred patients and their relatives were assessed at 2, 6, and 12 months post injury. Outcome variables included health-related quality of life (SF-12) as well as emotional, cognitive, interpersonal, and total functioning (PCRS). Relatives' physical health was predicted by relatives' PTS symptoms (Slope=-1.76; p = .043), and mental health was predicted by both patients' (Slope=-2.77; p = .034) and relatives' (Slope=-6.59; p < .001) PTS symptoms. Functioning level was only predicted by patients' PTS symptoms (Slope=-.25; p< .001). The findings emphasize that TBI should be considered a comprehensive traumatic experience reaching further than mere physical damage to the brain and its direct consequences, affecting the injured individual and close relatives.

El traumatismo craneoencefálico grave (TCEG) generalmente provoca una discapacidad duradera generalizada y está acompañado por una larga rehabilitación. Como es de esperarse, el TCEG también tiene consecuencias nocivas para los familiares cercanos de los pacientes. El agobio causado por la lesión y su gravedad explica algunas de las repercuciones en los familiares. Además, algunos resultados demuestran que los pacientes con TCEG y sus familiares desarrollan síntomas de estrés postraumático (EPT). Sin embargo, aunque la asociación entre los síntomas de EPT y la salud física y mental está bien documentada en la bibliografía, el efecto de los síntomas de EPT en los familiares de los pacientes con TCEG casi no se ha analizado. Este estudio analiza la influencia de los síntomas de EPT de los pacientes con TCEG y sus familiares en la salud física y mental y en el funcionamiento de los familiares. Se incluyó a pacientes que sufrieron un TCEG (escala abreviada de lesiones de la región craneana > 3) y a familiares cercanos en un estudio de cohorte prospectivo realizado en varios centros (TRAST-MI). Se evaluó a cien pacientes y a sus familiares a los dos, a los seis y a los doce meses después de la lesión. Entre los criterios de valoración se encontraron la calidad de vida relacionada con la salud (SF-12) así como el funcionamiento emocional, cognitivo, interpersonal y total (PCRS). La salud física de los familiares se predijo mediante los síntomas de EPT de los familiares (Pendiente = -1.76; p = .043), y la salud mental se predijo mediante los síntomas de EPT de los pacientes (Pendiente = -2.77; p = .034) y los familiares (Pendiente = -6.59; p < .001). El nivel de funcionamiento solo se predijo mediante los síntomas de EPT de los pacientes (Pendiente = -.25; p < .001). Los resultados enfatizan que el TCE debe considerarse una experiencia traumática amplia que va más allá del mero daño físico al cerebro y sus consecuencias directas, y que afecta a la persona lesionada y a sus familiares cercanos.

High risk and low uptake of pre-exposure prophylaxis to prevent HIV acquisition in a national online sample of transgender men who have sex with men in the United States.

INTRODUCTION: Trans masculine people who have sex with cisgender ("cis") men ("trans MSM") may be at-risk for HIV infection when they have cis MSM partners or share needles for hormone or recreational drug injection. Limited data are available characterizing indications and uptake of pre-exposure prophylaxis (PrEP) in trans MSM. The aim of this study was to assess PrEP indication and uptake as a means of primary HIV prevention for adult trans MSM in the U.S. METHODS: Between November and December 2017, a national convenience sample of trans MSM in the U.S. (n = 857) was recruited using participatory methodologies and completed an online survey of demographics, HIV risk, PrEP, behavioural and psychosocial factors. Self-reported receptive anal sex or frontal/vaginal sex (with or without a condom) with a cis male sex partner in past six months was an eligibility criterion. A multivariable logistic regression procedure was used to model PrEP indications (yes/no) per an interpretation of U.S. Centers of Disease Control and Prevention recommendations among those without HIV (n = 843). RESULTS: The diverse sample was 4.9% Black; 22.1% Latinx ethnicity; 28.4% non-binary gender identity; 32.6% gay-identified; 82.7% on testosterone. Overall, 84.1% had heard of PrEP. Of these, 33.3% reported lifetime PrEP use (21.8% current and 11.5% past). Based on HIV behavioural risk profiles in the last six months, 55.2% of respondents had indications for PrEP. In a multivariable model, factors associated with PrEP indication included where met sex partners, not having sex exclusively with cismen, higher perceived HIV risk, greater number of partners and high cis male partner stigma (all p < 0.05). DISCUSSION: The majority of trans MSM in this sample had a PrEP indication. Stigma was associated with risk for HIV acquisition and represents a critical target for HIV biobehavioural prevention interventions for trans MSM, who appear to be underutilizing PrEP. CONCLUSIONS: Results from this study support the full inclusion of trans MSM in HIV biobehavioural prevention efforts. Public health interventions and programmes are needed to reach trans MSM that attend to general MSM risk factors as well as to vulnerabilities specific to trans MSM, including the context of stigma from cis male sexual partners.

Autosomal recessive limb-girdle and Miyoshi muscular dystrophies in the Netherlands: The clinical and molecular spectrum of 244 patients.

In this retrospective study, we conducted a clinico-genetic analysis of patients with autosomal recessive limb-girdle muscular dystrophy (LGMD) and Miyoshi muscular dystrophy (MMD). Patients were identified at the tertiary referral centre for DNA diagnosis in the Netherlands and included if they carried two mutations in CAPN3, DYSF, SGCG, SGCA, SGCB, SGCD, TRIM32, FKRP or ANO5 gene. DNA was screened by direct sequencing and multiplex ligand-dependent probe amplification (MLPA) analysis. A total of 244 patients was identified; 68 LGMDR1/LGMD2A patients with CAPN3 mutations (28%), 67 sarcoglycanopathy patients (LGMDR3-5/LGMD2C-E) (27%), 64 LGMDR12/LGMD2L and MMD3 patients with ANO5 mutations (26%), 25 LGMDR2/LGMD2B and MMD1 with DYSF mutations (10%), 21 LGMDR9/LGMD2I with FKRP mutations (9%) and one LGMDR8/LGMD2H patient with TRIM32 mutations (<1%). The estimated minimum prevalence of AR-LGMD and MMD in the Netherlands amounted to 14.4 × 10-6 . Thirty-three novel mutations were identified. A wide range in age of onset (0-72 years) and loss of ambulation (5-74 years) was found. Fifteen patients (6%) initially presented with asymptomatic hyperCKemia. Cardiac abnormalities were found in 35 patients (17%). Non-invasive ventilation was started in 34 patients (14%). Both cardiac and respiratory involvement occurs across all subtypes, stressing the need for screening in all included subtypes.