Short-Term Cannabidiol with Δ-9-Tetrahydrocannabinol in Parkinson's Disease: A Randomized Trial.

BACKGROUND: Cannabis use is frequent in Parkinson's disease (PD), despite inadequate evidence of benefits and risks. OBJECTIVE: The aim is to study short-term efficacy and tolerability of relatively high cannabidiol (CBD)/low Δ-9-tetrahydrocannabinol (THC) to provide preliminary data for a longer trial. METHODS: Persons with PD with ≥20 on motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) who had negative cannabis testing took cannabis extract (National Institute of Drug Abuse) oral sesame oil solution for 2 weeks, increasing to final dose of 2.5 mg/kg/day. Primary outcome was change in motor MDS-UPDRS from baseline to final dose. RESULTS: Participants were randomized to CBD/THC (n = 31) or placebo (n = 30). Mean final dose (CBD/THC group) was 191.8 ± 48.9 mg CBD and 6.4 ± 1.6 mg THC daily. Motor MDS-UPDRS was reduced by 4.57 (95% CI, -8.11 to -1.03; P = 0.013) in CBD/THC group, and 2.77 (-4.92 to -0.61; P = 0.014) in placebo; the difference between groups was non-significant: -1.80 (-5.88 to 2.27; P = 0.379). Several assessments had a strong placebo response. Sleep, cognition, and activities of daily living showed a treatment effect, favoring placebo. Overall adverse events were mild and reported more in CBD/THC than placebo group. On 2.5 mg/kg/day CBD plasma level was 54.0 ± 33.8 ng/mL; THC 1.06 ± 0.91 ng/mL. CONCLUSIONS: The brief duration and strong placebo response limits interpretation of effects, but there was no benefit, perhaps worsened cognition and sleep, and there was many mild adverse events. Longer duration high quality trials that monitor cannabinoid concentrations are essential and would require improved availability of research cannabinoid products in the United States. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Calcific Peritendinitis in the Gluteus Maximus Tendon.

BACKGROUND: Calcific tendinitis is classically a painful condition that most commonly affects the rotator cuff, but may infrequently involve other tendons. CASE REPORT: We discuss a 57-year-old man who presented to the emergency department with a 4-day history of right hip pain, described as the "worst pain in (his) life." The pain was first noticed at night and had progressively worsened. History, physical examination, and initial laboratory workup indicated an inflammatory vs. infectious process. Continued investigations with imaging techniques revealed the source of pain as calcific tendinitis involving the gluteus maximus tendon. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Symptoms of musculoskeletal pain in the emergency department are ubiquitous. In the proper clinical context, the diagnosis of calcific tendinitis, although uncommon, should be considered once emergent conditions are ruled out. Proper imaging techniques will facilitate accurate diagnosis, expedited pain management, and proper outpatient follow-up.

AtheroSpectrum Reveals Novel Macrophage Foam Cell Gene Signatures Associated With Atherosclerotic Cardiovascular Disease Risk.

BACKGROUND: Whereas several interventions can effectively lower lipid levels in people at risk for atherosclerotic cardiovascular disease (ASCVD), cardiovascular event risks remain, suggesting an unmet medical need to identify factors contributing to cardiovascular event risk. Monocytes and macrophages play central roles in atherosclerosis, but studies have yet to provide a detailed view of macrophage populations involved in increased ASCVD risk. METHODS: A novel macrophage foaming analytics tool, AtheroSpectrum, was developed using 2 quantitative indices depicting lipid metabolism and the inflammatory status of macrophages. A machine learning algorithm was developed to analyze gene expression patterns in the peripheral monocyte transcriptome of MESA participants (Multi-Ethnic Study of Atherosclerosis; set 1; n=911). A list of 30 genes was generated and integrated with traditional risk factors to create an ASCVD risk prediction model (30-gene cardiovascular disease risk score [CR-30]), which was subsequently validated in the remaining MESA participants (set 2; n=228); performance of CR-30 was also tested in 2 independent human atherosclerotic tissue transcriptome data sets (GTEx [Genotype-Tissue Expression] and GSE43292). RESULTS: Using single-cell transcriptomic profiles (GSE97310, GSE116240, GSE97941, and FR-FCM-Z23S), AtheroSpectrum detected 2 distinct programs in plaque macrophages-homeostatic foaming and inflammatory pathogenic foaming-the latter of which was positively associated with severity of atherosclerosis in multiple studies. A pool of 2209 pathogenic foaming genes was extracted and screened to select a subset of 30 genes correlated with cardiovascular event in MESA set 1. A cardiovascular disease risk score model (CR-30) was then developed by incorporating this gene set with traditional variables sensitive to cardiovascular event in MESA set 1 after cross-validation generalizability analysis. The performance of CR-30 was then tested in MESA set 2 (P=2.60×10-4; area under the receiver operating characteristic curve, 0.742) and 2 independent data sets (GTEx: P=7.32×10-17; area under the receiver operating characteristic curve, 0.664; GSE43292: P=7.04×10-2; area under the receiver operating characteristic curve, 0.633). Model sensitivity tests confirmed the contribution of the 30-gene panel to the prediction model (likelihood ratio test; df=31, P=0.03). CONCLUSIONS: Our novel computational program (AtheroSpectrum) identified a specific gene expression profile associated with inflammatory macrophage foam cells. A subset of 30 genes expressed in circulating monocytes jointly contributed to prediction of symptomatic atherosclerotic vascular disease. Incorporating a pathogenic foaming gene set with known risk factors can significantly strengthen the power to predict ASCVD risk. Our programs may facilitate both mechanistic investigations and development of therapeutic and prognostic strategies for ASCVD risk.

High Frequency of Antibiotic Prescription in Children With Undifferentiated Febrile Illness in Kenya.

BACKGROUND: In low-resource, malaria-endemic settings, accurate diagnosis of febrile illness in children is challenging. The World Health Organization (WHO) currently recommends laboratory-confirmed diagnosis of malaria prior to starting treatment in stable children. Factors guiding management of children with undifferentiated febrile illness outside of malaria are not well understood. METHODS: This study examined clinical presentation and management of a cohort of febrile Kenyan children at 5 hospital/clinic sites from January 2014 to December 2017. Chi-squared and multivariate regression analyses were used to compare frequencies and correlate demographic, environmental, and clinical factors with patient diagnosis and prescription of antibiotics. RESULTS: Of 5735 total participants, 68% were prescribed antibiotic treatment (n = 3902), despite only 28% given a diagnosis of bacterial illness (n = 1589). Factors associated with prescription of antibiotic therapy included: negative malaria testing, reporting head, ears, eyes, nose and throat (HEENT) symptoms (ie, cough, runny nose), HEENT findings on exam (ie, nasal discharge, red throat), and having a flush toilet in the home (likely a surrogate for higher socioeconomic status). CONCLUSION: In a cohort of acutely ill Kenyan children, prescription of antimalarial therapy and malaria test results were well correlated, whereas antibiotic treatment was prescribed empirically to most of those who tested malaria negative. Clinical management of febrile children in these settings is difficult, given the lack of diagnostic testing. Providers may benefit from improved clinical education and implementation of enhanced guidelines in this era of malaria testing, as their management strategies must rely primarily on critical thinking and decision-making skills.

Recreational ketamine-induced cholangiopathy and ulcerative cystitis.

Ketamine is a versatile analgesic that has become an increasingly popular recreational drug. Chronic ketamine use has been found to cause biliary duct damage and bladder dysfunction. Ketamine-induced cholangiopathy and ulcerative cystitis are uncommon diagnoses presenting with nonspecific symptoms, creating diagnostic challenges for emergency physicians. We report a case of a teenage patient with the rare simultaneous presentation of ketamine-induced cholangiopathy and ulcerative cystitis. Due to increased recreational and chronic ketamine use, cases of ketamine-induced cholangiopathy and ulcerative cystitis are likely to rise with the increased knowledge, awareness, and reporting of these entities by radiologists and emergency physicians.

High Dengue Burden and Circulation of 4 Virus Serotypes among Children with Undifferentiated Fever, Kenya, 2014-2017.

Little is known about the extent and serotypes of dengue viruses circulating in Africa. We evaluated the presence of dengue viremia during 4 years of surveillance (2014-2017) among children with febrile illness in Kenya. Acutely ill febrile children were recruited from 4 clinical sites in western and coastal Kenya, and 1,022 participant samples were tested by using a highly sensitive real-time reverse transcription PCR. A complete case analysis with genomic sequencing and phylogenetic analyses was conducted to characterize the presence of dengue viremia among participants during 2014-2017. Dengue viremia was detected in 41.9% (361/862) of outpatient children who had undifferentiated febrile illness in Kenya. Of children with confirmed dengue viremia, 51.5% (150/291) had malaria parasitemia. All 4 dengue virus serotypes were detected, and phylogenetic analyses showed several viruses from novel lineages. Our results suggests high levels of dengue virus infection among children with undifferentiated febrile illness in Kenya.

Colocolic intussusception secondary to submucosal lipoma.

Adult intussusception is an uncommon cause of abdominal pain and poses diagnostic challenges for emergency physicians due to its varied presenting symptoms and time course. We report a case of chronic colocolic intussusception secondary to a lead point submucosal lipoma. Dedifferentiating intussusception with or without a lead point is important in determining appropriate management.

Three unsuspected CT diagnoses of COVID-19.

PURPOSE: Coronavirus disease 2019 (COVID-19) is caused by a novel strain of coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has quickly spread around the globe. Health care facilities in the USA currently do not have an adequate supply of COVID-19 tests to meet the growing demand. Imaging findings for COVID-19 are non-specific but include pulmonary parenchymal ground-glass opacities in a predominantly basal and peripheral distribution. METHODS: Three patients were imaged for non-respiratory-related symptoms with a portion of the lungs in the imaged field. RESULTS: Each patient had suspicious imaging findings for COVID-19, prompting the interpreting radiologist to suggest testing for COVID-19. All 3 patients turned out to be infected with COVID-19, and one patient is the first reported case of the coincident presentation of COVID-19 and an intraparenchymal hemorrhage. CONCLUSION: Using imaging characteristics of COVID-19 on abdominal or neck CT when a portion of the lungs is included, patients not initially suspected of COVID-19 infection can be quarantined earlier to limit exposure to others.

Unrecognized Dengue Virus Infections in Children, Western Kenya, 2014-2015.

We detected a cluster of dengue virus infections in children in Kenya during July 2014-June 2015. Most cases were serotype 1, but we detected all 4 serotypes, including co-infections with 2 serotypes. Our findings implicate dengue as a cause of febrile illness in this population and highlight a need for robust arbovirus surveillance.

Principles, practices and knowledge of clinicians when assessing febrile children: a qualitative study in Kenya.

BACKGROUND: Clinicians in low resource settings in malaria endemic regions face many challenges in diagnosing and treating febrile illnesses in children. Given the change in WHO guidelines in 2010 that recommend malaria testing prior to treatment, clinicians are now required to expand the differential when malaria testing is negative. Prior studies have indicated that resource availability, need for additional training in differentiating non-malarial illnesses, and lack of understanding within the community of when to seek care play a role in effective diagnosis and treatment. The objective of this study was to examine the various factors that influence clinician behavior in diagnosing and managing children presenting with fever to health centres in Kenya. METHODS: A total of 20 clinicians (2 paediatricians, 1 medical officer, 2 nurses, and 15 clinical officers) were interviewed, working at 5 different government-sponsored public clinic sites in two areas of Kenya where malaria is prevalent. Clinicians were interviewed one-on-one using a structured interview technique. Interviews were then analysed qualitatively for themes. RESULTS: The following five themes were identified: (1) Strong familiarity with diagnosis of malaria and testing for malaria; (2) Clinician concerns about community understanding of febrile illness, use of traditional medicine, delay in seeking care, and compliance; (3) Reliance on clinical guidelines, history, and physical examination to diagnose febrile illness and recognize danger signs; (4) Clinician discomfort with diagnosis of primary viral illness leading to increased use of empiric antibiotics; and (5) Lack of resources including diagnostic testing, necessary medications, and training modalities contributes to the difficulty clinicians face in assessing and treating febrile illness in children. These themes persisted across all sites, despite variation in levels of medical care. Within these themes, clinicians consistently expressed a need for reliable basic testing, especially haemograms and bacterial cultures. Clinicians discussed the use of counseling and education to improve community understanding of febrile illness in order to decrease preventable deaths in children. CONCLUSION: Results of this study suggest that since malarial testing has become more widespread, clinicians working in resource-poor environments still face difficulty when evaluating a child with fever, especially when malaria testing is negative. Improving access to additional diagnostics, continuing medical education, and ongoing evaluation and revision of clinical guidelines may lead to more consistent management of febrile illness by providers, and may potentially decrease prescription of unnecessary antibiotics. Additional interventions at the community level may also have an important role in managing febrile illness, however, more studies are needed to identify targets for intervention at both the clinic and community levels.

IL-33 induces nuocytes and modulates liver injury in viral hepatitis.

Molecules containing damage-associated molecular patterns play an important role in many pathogenic processes. In this study, our aim was to investigate the role of IL-33, a damage-associated molecular pattern molecule, in adenovirus (Ad)-induced liver inflammation. Ad-infected mice exhibited a steadily increased IL-33 and its receptor IL-1R-like 1 expression in the liver during the first week of infection. Treatment of exogenous IL-33 resulted in a great decrease in the serum alanine aminotransferase levels and the number of Councilman bodies in the liver. Attenuated liver injury by IL-33 correlated with an increase in T regulatory cells but with a decrease in macrophages, dendritic cells, and NK cells in the liver. IL-33 enhanced both type 1 (IL-2 and IFN-γ) and type 2 (IL-5 and IL-13) immune responses in infected mice. However, IL-33 inhibited TNF-α expression in hepatic T cells and macrophages, and significantly reduced TNF-α levels in the liver. We found that in addition to its direct effects, IL-33 strongly induced novel nuocytes in the livers and spleens of infected mice. When cocultured with nuocytes, hepatic T cells and macrophages expressed lower levels of TNF-α. The IL-33-treated mice also demonstrated a slight delay, but no significant impairment, in eliminating an intrahepatic infection with Ad. In conclusion, this study reveals that IL-33 acts as a potent immune stimulator and a hepatoprotective cytokine in acute viral hepatitis. Its direct immunoregulatory functions and ability to induce novel nuocytes further suggest to us that it may be a potentially promising therapeutic candidate for the management of viral hepatitis.

Course of the mandibular incisive canal and its impact on harvesting symphysis bone grafts.

PURPOSE: To characterize the anatomic course of the mandibular incisive canal to define parameters for harvesting autogenous bone from the symphysis of the mandible. MATERIALS AND METHODS: A series of osteotomies were completed between the mental foramina in the anterior mandibles of 19 cadavers. Methylene blue dye was used to help identify the incisive canal. From the canal, distances to key adjacent landmarks were measured with a Boley gauge to 0.1 mm. Measurements included distances from the mandibular incisive canal to the buccal cortex, the lingual cortex, the inferior border of the mandible, the apices of the teeth, and the buccal cementoenamel junction (CEJ) of the teeth. RESULTS: The canal decreased in diameter from lateral to medial. It tended to be closer to the buccal cortical bone than to the lingual cortex (P < .001) and was, at times, directly abutting the buccal cortex (average distance to buccal cortex, 3.5 mm). The canal maintained a relatively constant distance from the apices of the teeth (approximately 7 to 8 mm), coursing inferiorly under the longer canines bilaterally. The canal became increasingly difficult to identify toward the midline, likely dispersing into microscopic tributaries. CONCLUSIONS: The authors suggest several modifications to the standard surgical approach to the symphysis area during the harvest of bone grafts. When the goal is to avoid the mandibular incisive canal, osteotomies should not exceed a depth of 4 mm, should be at least 5 mm anterior to the mental foramen, and 9 mm below the root apices (or 23 mm below the lowest facial CEJ) and should maintain the contour of the mandible's inferior border. Alternatively, some degree of canal compromise can be accepted and larger grafts can be obtained by increasing the depth of the harvest in the horizontal dimension or decreasing the distance from the osteotomy to the root apices (or the CEJ) in the vertical dimension.

Inhibition of the alternative pathway of nonhuman infant complement by porin B2 contributes to virulence of Neisseria meningitidis in the infant rat model.

Neisseria meningitidis utilizes capsular polysaccharide, lipooligosaccharide (LOS) sialic acid, factor H binding protein (fHbp), and neisserial surface protein A (NspA) to regulate the alternative pathway (AP) of complement. Using meningococcal mutants that lacked all four of the above-mentioned molecules (quadruple mutants), we recently identified a role for PorB2 in attenuating the human AP; inhibition was mediated by human fH, a key downregulatory protein of the AP. Previous studies showed that fH downregulation of the AP via fHbp or NspA is specific for human fH. Here, we report that PorB2-expressing quadruple mutants also regulate the AP of baby rabbit and infant rat complement. Blocking a human fH binding region on PorB2 of the quadruple mutant of strain 4243 with a chimeric protein that comprised human fH domains 6 and 7 fused to murine IgG Fc enhanced AP-mediated baby rabbit C3 deposition, which provided evidence for an fH-dependent mechanism of nonhuman AP regulation by PorB2. Using isogenic mutants of strain H44/76 that differed only in their PorB molecules, we confirmed a role for PorB2 in resistance to killing by infant rat serum. The PorB2-expressing strain also caused higher levels of bacteremia in infant rats than its isogenic PorB3-expressing counterpart, thus providing a molecular basis for increased survival of PorB2 isolates in this model. These studies link PorB2 expression with infection of infant rats, which could inform the choice of meningococcal strains for use in animal models, and reveals, for the first time, that PorB2-expressing strains of N. meningitidis regulate the AP of baby rabbits and rats.

Interleukin-1ß triggers the differentiation of macrophages with enhanced capacity to present mycobacterial antigen to T cells.

The rapid differentiation of monocytes into macrophages (MΦ) and dendritic cells is a pivotal aspect of the innate immune response. Differentiation is triggered following recognition of microbial ligands that activate pattern recognition receptors or directly by pro-inflammatory cytokines. We demonstrate that interleukin-1ß (IL-1ß) induces the rapid differentiation of monocytes into CD209(+) MΦ, similar to activation via Toll-like receptor 2/1, but with distinct phenotypic and functional characteristics. The IL-1ß induced MΦ express higher levels of key markers of phagocytosis, including the Fc-receptors CD16 and CD64, as well as CD36, CD163 and CD206. In addition, IL-1ß-induced MΦ exert potent phagocytic activity towards inert particles, oxidized low-density lipoprotein and mycobacteria. Furthermore, IL-1ß-induced MΦ express higher levels of HLA-DR and effectively present mycobacterial antigens to T cells. Therefore, the ability of IL-1ß to induce monocyte differentiation into MΦ with both phagocytosis and antigen-presenting function is a distinct part of the innate immune response in host defence against microbial infection.

A pleckstrin homology-related domain in SHIP1 mediates membrane localization during Fcγ receptor-induced phagocytosis.

SH2 domain-containing inositol-5'-phosphatase-1 (SHIP1) inhibits inflammation by hydrolyzing phosphoinositide-3'-kinase generated membrane phosphatidylinositol-3,4,5-trisphosphate (PIP(3)). Bioinformatic analysis of SHIP1 from multiple species revealed a pleckstrin homololgy-related (PH-R) domain, which we hypothesize mediates SHIP1's association with the membrane, a requirement for its biological function. Recombinant murine SHIP1 PH-R domain was subjected to biophysical and biochemical analysis. Residues K370 and K397 were found to be important for PH-R domain association with membrane PIP(3). Wild-type PH-R domain bound PIP(3) with 1.9 ± 0.2 nM affinity, while the affinity of a K370A/K397A substituted mutant was too low to measure. Wild-type (but not the K370A/K397A substituted) full-length SHIP1 protein, reconstitutes normal inhibition of Fcγ receptor-mediated phagocytosis when introduced into SHIP1(-/-) murine macrophages, reducing the number of phagocytic events by 2-fold as compared to SHIP1(-/-) cells. In fact, the PH-R-mediated membrane interaction appears to be a major mechanism by which SHIP1 is recruited to the membrane, since the K370A/K397A substitution reduced the recruitment of both full-length SHIP1 and the PH-R domain by ≥2-fold. We have previously shown that SHIP1 enzyme activity can be targeted for therapeutic purposes. The current studies suggest that molecules targeting the PH-R domain can also modulate SHIP1 function.

Primary intramuscular and intermuscular Echinococcal disease of the iliopsoas and sartorius muscles: A case report.

Hydatid disease is a parasitic infection caused by the Echinococcus tapeworm. Classically, Echinococcal lesions are slowly growing cystic masses with daughter cysts. The most common sites of disease are the liver in 75% of cases and lungs in 15% of cases. This report covers a case of a patient from Southeast Europe with primary extrahepatic hydatid disease in and along the left iliopsoas and sartorius muscles. Retroperitoneal and soft tissue Echinococcus infection without liver involvement is extremely rare and creates a diagnostic challenge for clinicians and radiologists, especially in nonendemic areas.

Substance use and other correlates of HIV infection among transwomen and men who have sex with men in Perú: Implications for targeted HIV prevention strategies for transwomen.

Characterization of HIV risk factors among transwomen and men who have sex with men (MSM) should be assessed separately and independently. However, due to several constraints, these populations continue to be conflated in clinical research and data. There are limited datasets globally powered to make such comparisons. The study aimed to use one of the largest surveys of transwomen and MSM in Latin America to determine differences in HIV risk and related correlates between the two populations. Secondary data analysis was completed using a cross-sectional biobehavioral survey of 4413 MSM and 714 transwomen living in Perú. Chi Square analysis of selected HIV correlates was conducted to examine differences between transwomen and MSM. Additionally, stratified binary logistic regression was used to split data for further comparative analyses of correlates associated with transwomen and MSM separately. HIV prevalence among transwomen was two-fold greater than among MSM (14.9% vs. 7.0%, p<0.001). Transwomen had a higher prevalence of most HIV risk factors assessed, including presence of alcohol dependence (16.4% vs. 19.0%; p < .001) and drug use in the past 3 months (17.0% vs. 14.9%). MSM were more likely to use marijuana (68.0% vs. 50.0%, p < .001), and transwomen were more likely to engage in inhaled cocaine use (70.0% vs. 51.1%, p < .001). The regression exposed differences in correlates driving sub-epidemics in transwomen vs. MSM, with a trend of substance use increasing HIV risk for transwomen only. Transwomen were more likely to be HIV-infected and had different risk factors from MSM. Targeted prevention strategies are needed for transwomen that are at highest risk. Additionally, further research is needed to determine if these observations in Perú regarding substance use patterns and the role of substance use in HIV risk relate to other trans populations globally.

Detection of acute dengue virus infection, with and without concurrent malaria infection, in a cohort of febrile children in Kenya, 2014-2019, by clinicians or machine learning algorithms.

Poor access to diagnostic testing in resource limited settings restricts surveillance for emerging infections, such as dengue virus (DENV), to clinician suspicion, based on history and exam observations alone. We investigated the ability of machine learning to detect DENV based solely on data available at the clinic visit. We extracted symptom and physical exam data from 6,208 pediatric febrile illness visits to Kenyan public health clinics from 2014-2019 and created a dataset with 113 clinical features. Malaria testing was available at the clinic site. DENV testing was performed afterwards. We randomly sampled 70% of the dataset to develop DENV and malaria prediction models using boosted logistic regression, decision trees and random forests, support vector machines, naïve Bayes, and neural networks with 10-fold cross validation, tuned to maximize accuracy. 30% of the dataset was reserved to validate the models. 485 subjects (7.8%) had DENV, and 3,145 subjects (50.7%) had malaria. 220 (3.5%) subjects had co-infection with both DENV and malaria. In the validation dataset, clinician accuracy for diagnosis of malaria was high (82% accuracy, 85% sensitivity, 80% specificity). Accuracy of the models for predicting malaria diagnosis ranged from 53-69% (35-94% sensitivity, 11-80% specificity). In contrast, clinicians detected only 21 of 145 cases of DENV (80% accuracy, 14% sensitivity, 85% specificity). Of the six models, only logistic regression identified any DENV case (8 cases, 91% accuracy, 5.5% sensitivity, 98% specificity). Without diagnostic testing, interpretation of clinical findings by humans or machines cannot detect DENV at 8% prevalence. Access to point-of-care diagnostic tests must be prioritized to address global inequities in emerging infections surveillance.

Enhanced bacteremia in human factor H transgenic rats infected by Neisseria meningitidis.

Neisseria meningitidis binds the complement downregulating protein, factor H (fH), which enables the organism to evade host defenses. Two fH ligands, fHbp and NspA, are known to bind specifically to human fH. We developed a human fH transgenic infant rat model to investigate the effect of human fH on meningococcal bacteremia. At 18 h after intraperitoneal challenge with 560 CFU of group B strain H44/76, all 19 human fH-positive rats had positive blood cultures compared to 0 of 7 human fH-negative control littermates (P < 0.0001). Human fH-positive infant rats also developed bacteremia after challenge with isogenic mutants of H44/76 in which genes encoding fHbp and NspA (ΔfHbp ΔNspA mutant) or the lipooligosaccharide sialyltransferase (Δlst mutant) had been inactivated. A fully encapsulated ΔfHbp ΔNspA Δlst mutant unable to sialylate lipooligosaccharide or bind human fH via the known fH ligands did not cause bacteremia, which argued against global susceptibility to bacteremia resulting from random integration of the transgene into the rat genome. In vitro, the wild-type and ΔfHbp ΔNspA mutant strains were killed by as little as 20% wild-type infant rat serum. The addition of 3 µg of human fH/ml permitted survival of the wild-type strain in up to 60% infant rat serum, whereas ≥33 µg of human fH/ml was required to rescue the ΔfHbp ΔNspA mutant. The ability of meningococci lacking expression of fHbp and NspA to cause invasive disease in human fH transgenic rats and to survive in wild-type infant rat serum supplemented with human fH indicates an additional human fH-dependent mechanism of evasion of innate immunity.

Prevalence of Intimate Partner Violence, Substance Use Disorders and Depression among Incarcerated Women in Lima, Perú.

BACKGROUND: Globally, there is evidence supporting the co-occurrence of intimate partner violence (IPV), substance use disorders (SUD) and mental health disorders among women in prisons, however, there is limited research investigating these domains in the Andean region where rates of female incarceration have increased. The study objective was to explore the prevalence of IPV, SUD and depression among incarcerated women in a Peruvian prison and explore associations among these variables and related correlates. METHODS: 249 incarcerated women responded to a questionnaire about IPV, substance use, depression, and sexual behavior, and were screened for HIV/sexually transmitted diseases (STDs). Univariate analysis and logistic regression were used to estimate relative risk and the influence of substance use and depression on IPV rates. RESULTS: Twelve months prior to incarceration, of the women with sexual partners pre-incarceration (n = 212), 69.3% experienced threats of violence, 61.4% experienced ≥1 acts of physical violence, and 28.3% reported ≥1 act of sexual aggression. Pre-incarceration, 68.1% of drug-using women had a SUD, and 61.7% of those who consumed alcohol reported hazardous/harmful drinking. There were 20 (8.0%) HIV/STD cases; and 67.5% of the women reported depressive symptoms. Compared to women with no experiences of physical violence, a greater proportion of women who experienced least l violent act had depressive symptoms and engaged in sex work pre-incarceration. Depression was associated with physical violence (adjusted relative risk = 1.35, 95% confidence interval: 1.14-1.58). RECOMMENDATIONS: The findings provide evidence of a syndemic of IPV, substance abuse and depression among incarcerated women in a Peruvian prison. To help guide policy makers, further research is needed to determine if this is indicative of trends for other at-risk women in the region, and viable options to treat these women during incarceration to prevent recidivism and other long-term negative sequalae.