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IMPORTANCE:. Approximately 50% of clinicians experience excessive emotional, physical, and mental stress, with repercussions across the entire medical system. Mindfulness exercises may mitigate this excessive stress. Heart rate variability (HRV) is an objective stress measure that can quantify which mindfulness exercises provide the greatest stress reduction. OBJECTIVES:. To define the impact of specific mindfulness exercises on HRV, a surrogate for physiologic stress, and the relationship between physiologic (HRV) and subjective stress measured by the State-Trait Anxiety Inventory during a one-day mindfulness workshop. DESIGN, SETTING, AND PARTICIPANTS:. This was a prospective observational pilot study performed at a quaternary children’s hospital with diverse subspecialists of pediatric nurses, nurse practitioners, and physicians. MAIN OUTCOMES AND MEASURES:. Our primary outcome measure was change in HRV from baseline during three mindfulness exercises. RESULTS:. The grounding, deep breathing, and body scan exercises all produced statistically significant changes in HRV among our 13 female participants. The body scan exercise produced statistically significant changes in all studied HRV parameters compared with baseline. We observed significant increases in Root Mean Square of Successive Differences between normal heartbeats (p = 0.026), high frequency (p ≤ 0.001), and the parasympathetic nervous system index (p ≤ 0.001) reflecting increased parasympathetic tone (e.g., relaxation), whereas sd 2/sd 1 ratio (p ≤ 0.001) and the stress index (p = 0.004) were decreased reflecting sympathetic withdrawal (e.g., decreased stress). Subjective stress decreased after 1-day mindfulness training (44.6 to 27.2) (p < 0.001). Individuals with the largest decrease in subjective stress also had the most improvement in HRV during the body scan exercise. CONCLUSIONS:. Clinician stress levels (HRV) improved after participating in grounding, deep breathing, and body scan meditations, which may highlight their importance as stress reduction tools for clinicians. Monitoring of HRV during mindfulness exercises may provide deeper understanding of which specific exercises produce the greatest physiologic stress reduction for individual participants and the trend of these changes over time.

Abstract:. This article is a technical note to outline a novel technique of fixation in complex, comminuted distal radius fractures using a double-locked K-wire construct using a new implant called K-lock. In these (AO) C-type fractures, with significant dorsal comminution, it is often difficult to attain stable and secure fixation of the dorsal rim fragments, especially the dorsal lunate fossa fragment. This often results in patients being treated by temporary spanning devices or asking to have a restricted use of the hand during a given period to avoid loss of position. If dorsal plating is necessary, because of the severity of the comminution, a double-locked K-wire (locked in both the dorsal and volar plates) offers a fixation option and may create a significantly stronger construct and allow confident early mobilization. The K-lock was recently launched by Newclip Technics as an adjunct to the Xpert Wrist 2.4 set as a fragment-specific fixation option. The wire has less chance of displacing or fracturing the fragment and has a smooth surface compared with a screw; this wire would be safer close to the joint in severe distal intra-articular comminution. Of the 9 cases performed so far (as is our usual practice), despite the complexity of the fractures, none were immobilized postoperatively and all started hand therapy in the first week. Most were driving by 2 weeks and returned to light work at 4 weeks and heavy work or sports at 6 to 8 weeks. This principle of fixation may also be extended to other fractures where dual plating is used.

OBJECTIVES:. This study had three aims: 1) quantify the difference in stress levels between low and high stress roles during simulated critical communication encounters using objective physiologic data (heart rate variability [HRV]) and subjective measures (State-Trait Anxiety Inventory [STAI]), 2) define the relationship between subjective and objective measures of stress, and 3) define the impact of trainee preparedness and reported self-efficacy on stress levels. DESIGN:. Mixed methods simulation-based study. SETTING:. Single center. PATIENTS:. Pediatric critical care fellows and faculty (n = 12). INTERVENTIONS:. Subjects participated in six simulated scenarios in both high stress “hot seat” and low stress “observer” roles. MEASUREMENTS AND MAIN RESULTS:. Subjective stress was measured using the STAI at baseline and after each scenario. Objective stress was measured continuously using a wearable biometric device measuring HRV. Previous residency communication training and self-confidence surrounding various communication topics were collected via questionnaire. Significant changes in subjective (STAI) and objective stress (HRV) measurements in the low- versus high-stress roles were observed. STAI scores increased 8 points during low stress and 12 points during high stress role (p = 0.021) compared with baseline. Two specific HRV markers, root mean square of successive differences between normal heartbeats, a marker of parasympathetic tone, and the low frequency/high frequency (LF/HF) ratio, a marker of sympathetic activation, were significantly correlated with STAI levels (–0.032, p = 0.001; 1.030, p = 0.002, respectively). Participants who reported increased confidence in discussing code status had a significant decrease in stress response (measured via LF/HF ratio) during both the observer (p = 0.033) and hot seat roles (p =

Transcatheter aortic valve replacement is currently used off-label for noncalcified aortic valve regurgitation and therefore is restricted to selected cases. In this setting we describe a rare complication of Sapien 3 (Edwards Lifesciences, Irvine, California) embolization from the left ventricle to the descending aorta. Given their technical challenges, such procedures require specific considerations and management. (Level of Difficulty: Advanced.)

Background Decisional conflict (DC) is a psychological construct that an individual experiences in making a decision that involves risk, loss, regret, or challenges to one’s values. This study assessed DC in a cohort of South African men undergoing curative treatment for localised prostate cancer (LPC). The objectives were to (1) to examine the association between DC and prostate cancer knowledge (PCK), demographics, state anxiety, prostate cancer anxiety and time to treatment and (2) to compare levels of DC between treatment groups [prostatectomy (RP) and external beam radiation (RT)]. Method Data, comprising the Decisional Conflict Scale (DCS), Prostate Cancer Knowledge (PCK), State-Trait Anxiety Inventory (STAI-S), the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) and demographic data from 83 participants of a larger prospective longitudinal observational study examining depression, anxiety and health related quality of life (DAHCaP) were analysed. Results The mean age of participants was 63 years (RP 61yrs and RT 65yrs; p< 0.001). Most were of mixed ancestry (72.3%). The total DCS scores between the treatment groups (RP 25.00 and RT 18.75; p = 0.037) and two DCS sub-scores-uncertainty (p = 0.033 ) , and support (p = 0.048 ), were significantly higher in the RP group. A statistically significant negative correlation was observed between state anxiety and time between diagnosis and treatment in the RP group (Spearman’s rho = −0.368; p = 0.030). There was no correlation between the DCS score and PCK within each treatment group (Spearman’s rho RP = −0.249 and RT = −0.001). Conclusion Decisional conflict was higher in men undergoing RP. Men were more anxious in the RP group regarding the time treatment was received from diagnosis. No correlation was observed between DC and PCK. Pre-surgical management of DC should include shared decision making (SDM) which is cognisant of patients’ values facilitated by a customised decision aid.

Background: Traumatic atlantoaxial rotatory subluxation (TAARS) in adults is rare. We present an uncommon case of traumatic atlantoaxial rotatory subluxation with an associated type II odontoid fracture in a neurologically intact patient and describe a novel technique used for a successful closed reduction. Case description: A 20-year-old female presented with a decreased level of consciousness after being involved in a motor vehicle accident at highway speeds. A computed tomography (CT) demonstrated atlantoaxial rotatory subluxation and a type II odontoid fracture. CT angiography showed a left V3 vertebral dissection. She was neurologically intact on examination. A halo ring was applied and the patient successfully underwent closed reduction using traction and a novel transoral reduction technique described below.After closed reduction, a C1–C2 posterior instrumented fusion was performed. At 12-weeks follow-up, the patient was asymptomatic, neurologically intact with optimally maintained cervical spine alignment. Conclusion: Prompt manual closed reduction can safely be achieved in adults using this novel transoral reduction technique, which we describe for the first time in this report. Keywords: Case report, Traumatic atlantoaxial rotatory subluxation, Closed reduction, Type II odontoid fracture

RNA-binding proteins (RBPs) are a major class of proteins that interact with RNAs to change their fate or function. RBPs and the ribonucleoprotein complexes they constitute are involved in many essential cellular processes. In many cases, the molecular details of RBP:RNA interactions differ between viruses, prokaryotes and eukaryotes, making prokaryotic and viral RBPs good potential drug targets. However, targeting RBPs with small molecules has so far been met with limited success as RNA-binding sites tend to be extended, shallow and dynamic with a mixture of charged, polar and hydrophobic interactions. Here, we show that peptide nucleic acids (PNAs) with nucleic acid-like binding properties and a highly stable peptide-like backbone can be used to target some RBPs. We have designed PNAs to mimic the short RNA stem-loop sequence required for the initiation of prokaryotic signal recognition particle (SRP) assembly, a target for antibiotics development. Using a range of biophysical and biochemical assays, the designed PNAs were demonstrated to fold into a hairpin structure, bind the targeted protein and compete with the native RNA hairpin to inhibit SRP formation. To show the applicability of PNAs against other RBPs, a PNA was also shown to bind Nsp9 from SARS-CoV-2, a protein that exhibits non-sequence-specific RNA binding but preferentially binds hairpin structures. Taken together, our results support that PNAs can be a promising class of compounds for targeting RNA-binding activities in RBPs., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Zhong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model. Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice assessed with a multiplex assay, and tumor molecular biology and histology characterized with Western blotting and H&E histological staining. Results: WT tumor-bearing mice had increased levels of plasma SAA compared to wild-type control mice, while SAADKO control and tumor-bearing mice presented with lower levels of SAA in their plasma. SAADKO tumor-bearing mice also displayed significantly lower concentrations of systemic inflammatory markers. Tumors from SAADKO mice overall had lower levels of SAA compared to tumors from wild-type mice, decreased apoptosis and inflammasome signaling, and little to no tumor necrosis. Conclusions: We demonstrated that systemic SAA1/2 stimulates the activation of the NLRP3 inflammasome in breast tumors, leading to the production of pro-inflammatory cytokines. This, in turn, promoted apoptosis and tumor necrosis but did not significantly impact tumor growth or histological grading.

Detailed insights into protein structure/function relationships require robust characterization methodologies. Free-solution capillary electrophoresis (CE) is a unique separation technique which is sensitive to the conformation and/or composition of proteins, and therefore provides information on the heterogeneity of these properties. Three unrelated, conformationally/compositionally-altered proteins were separated by CE. An electrophoretic mobility distribution was determined for each protein along with its conformational and/or compositional heterogeneity. The CE results were compared with molar mass distributions obtained from size-exclusion chromatography coupled to light scattering (SEC-MALS). Bovine serum albumin multimers and two monomeric species were separated, highlighting variations in conformational/compositional heterogeneity among the multimers. Analysis of yeast alcohol dehydrogenase resolved two monomeric conformers and various tetrameric species, illustrating the impact of zinc ion removal and disulfide bond reduction on the protein's heterogeneity. The apo (calcium-free) and holo forms of bovine α-lactalbumin were separated and differences in the species' heterogeneity were measured; by contrast, the SEC-MALS profiles were identical. Comparative analysis of these structurally unrelated proteins provided novel insights into the interplay between molar mass and conformational/compositional heterogeneity. Overall, this study expands the utility of CE by demonstrating its capacity to discern protein species and their heterogeneity, properties which are not readily accessible by other analytical techniques., (© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Cervical cancer is the fourth most common cancer in women. Advanced stage and metastatic disease are often associated with poor clinical outcomes. This substantiates the absolute necessity for high-throughput diagnostic and treatment platforms that are patient and tumour specific. Cervical cancer treatment constitutes multimodal intervention. Systemic treatments such as chemotherapy and/or focal radiotherapy are typically applied as neoadjuvant and/or adjuvant strategies. Cisplatin constitutes an integral part of standard cervical cancer treatment approaches. However, despite initial patient response, de novo or delayed/acquired treatment resistance is often reported, and toxicity is of concern. Chemotherapy resistance is associated with major alterations in genomic, metabolomic, epigenetic and proteomic landscapes. This results in imbalanced homeostasis associated with pro-oncogenic and proliferative survival, anti-apoptotic benefits, and enhanced DNA damage repair processes. Although significant developments in cancer diagnoses and treatment have been made over the last two decades, drug resistance remains a major obstacle to overcome., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The repair of double-strand DNA breaks (DSBs) by homologous recombination is crucial in the maintenance of genome integrity. While the key role of the Mre11-Rad50-Nbs1 (MRN) complex in repair is well known, hSSB1 (SOSSB and OBFC2B), one of the main components of the sensor of single-stranded DNA (SOSS) protein complex, has also been shown to rapidly localize to DSB breaks and promote repair. We have previously demonstrated that hSSB1 binds directly to Nbs1, a component of the MRN complex, in a DNA damage-independent manner. However, recruitment of the MRN complex has also been demonstrated by an interaction between Integrator Complex Subunit 3 (INTS3; also known as SOSSA), another member of the SOSS complex, and Nbs1. In this study, we utilize a combined approach of in silico, biochemical, and functional experiments to uncover the molecular details of INTS3 binding to Nbs1. We demonstrate that the forkhead-associated domain of Nbs1 interacts with INTS3 via phosphorylation-dependent binding to INTS3 at Threonine 592, with contributions from Serine 590. Based on these data, we propose a model of MRN recruitment to a DSB via INTS3., (© 2023 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

Interactions between the upper ocean and air-ice-ocean fluxes in the Southern Ocean play a critical role in global climate by impacting the overturning circulation and oceanic heat and carbon uptake. Remote and challenging conditions have led to sparse observational coverage, while ongoing field programmes often fail to collect sufficient information in the right place or at the time-space scales required to constrain the variability occurring in the coupled ocean-atmosphere system. Only within the last 10 years have we been able to directly observe and assess the role of the fine-scale ocean and rapidly evolving atmospheric marine boundary layer on the upper limb of the Southern Ocean's overturning circulation. This review summarizes advances in mechanistic understanding, arising in part from observational programmes using autonomous platforms, of the fine-scale processes (1-100 km, hours-seasons) influencing the Southern Ocean mixed layer and its variability. We also review progress in observing the ocean interior connections and the coupled interactions between the ocean, atmosphere and cryosphere that moderate air-sea fluxes of heat and carbon. Most examples provided are for the ice-free Southern Ocean, while major challenges remain for observing the ice-covered ocean. We attempt to elucidate contemporary research gaps and ongoing/future efforts needed to address them. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

The Southern Ocean greatly contributes to the regulation of the global climate by controlling important heat and carbon exchanges between the atmosphere and the ocean. Rates of climate change on decadal timescales are therefore impacted by oceanic processes taking place in the Southern Ocean, yet too little is known about these processes. Limitations come both from the lack of observations in this extreme environment and its inherent sensitivity to intermittent processes at scales that are not well captured in current Earth system models. The Southern Ocean Carbon and Heat Impact on Climate programme was launched to address this knowledge gap, with the overall objective to understand and quantify variability of heat and carbon budgets in the Southern Ocean through an investigation of the key physical processes controlling exchanges between the atmosphere, ocean and sea ice using a combination of observational and modelling approaches. Here, we provide a brief overview of the programme, as well as a summary of some of the scientific progress achieved during its first half. Advances range from new evidence of the importance of specific processes in Southern Ocean ventilation rate (e.g. storm-induced turbulence, sea-ice meltwater fronts, wind-induced gyre circulation, dense shelf water formation and abyssal mixing) to refined descriptions of the physical changes currently ongoing in the Southern Ocean and of their link with global climate. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

Objectives: Providing country-specific estimates of case fatality and sequelae from bacterial meningitis (BM) is important to evaluate and monitor progress toward the World Health Organization's roadmap to "defeating meningitis by 2030"., Methods: From 2016-2020, GERMS-SA conducted enhanced surveillance at 26 hospitals across South Africa. Episodes of laboratory-confirmed BM due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis were included. Risk factors for in-hospital death and sequelae at hospital discharge among survivors were analyzed., Results: Of 12,717 invasive bacterial infections reported nationally, 39% (4980) were from enhanced surveillance sites, including 4159 pneumococcal, 640 H. influenzae, and 181 meningococcal infections. BM accounted for 32% (1319/4159) of pneumococcal, 21% (136/640) of H. influenzae, and 83% (151/181) of meningococcal invasive diseases. Clinical data were available for 91% (1455/1606) of BM: 26% (376/1455) were aged <5 years, 50% (726/1455) were female, and 62% (723/1171) with known HIV results, were HIV-infected. In-hospital case fatality was 37% (534/1455), and 24% (222/921) of survivors had adverse sequelae. Risk factors for death included altered mental status, HIV infection, and comorbidities. Risk factors for adverse sequelae included altered mental status and antimicrobial nonsusceptibility., Conclusion: BM in South Africa has a high case fatality, and adverse sequelae frequently occur among survivors. Those with comorbidities (including HIV) are at the highest risk., Competing Interests: Declaration of Competing interest Susan Meiring reports a grant from Sanofi Pasteur for research outside the submitted work. Anne von Gottberg and Cheryl Cohen report grants from US CDC, PATH, Wellcome Trust, Sanofi, and from South African MRC, outside the submitted work. All other authors declare that they have no commercial or other associations that may pose a conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The subpolar Southern Ocean is a critical region where CO 2 outgassing influences the global mean air-sea CO 2 flux (F CO2 ). However, the processes controlling the outgassing remain elusive. We show, using a multi-glider dataset combining F CO2 and ocean turbulence, that the air-sea gradient of CO 2 (∆pCO 2 ) is modulated by synoptic storm-driven ocean variability (20 µatm, 1-10 days) through two processes. Ekman transport explains 60% of the variability, and entrainment drives strong episodic CO 2 outgassing events of 2-4 mol m -2 yr -1 . Extrapolation across the subpolar Southern Ocean using a process model shows how ocean fronts spatially modulate synoptic variability in ∆pCO 2 (6 µatm 2 average) and how spatial variations in stratification influence synoptic entrainment of deeper carbon into the mixed layer (3.5 mol m -2 yr -1 average). These results not only constrain aliased-driven uncertainties in F CO2 but also the effects of synoptic variability on slower seasonal or longer ocean physics-carbon dynamics., (© 2022. The Author(s).)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel, highly infectious RNA virus that belongs to the coronavirus family. Replication of the viral genome is a fundamental step in the virus life cycle and SARS-CoV-2 non-structural protein 9 (Nsp9) is shown to be essential for virus replication through its ability to bind RNA in the closely related SARS-CoV-1 strain. Two recent studies revealing the three-dimensional structure of Nsp9 from SARS-CoV-2 have demonstrated a high degree of similarity between Nsp9 proteins within the coronavirus family. However, the binding affinity to RNA is very low which, until now, has prevented the determination of the structural details of this interaction. In this study, we have utilized nuclear magnetic resonance spectroscopy (NMR) in combination with surface biolayer interferometry (BLI) to reveal a distinct binding interface for both ssDNA and RNA that is different to the one proposed in the recently solved SARS-CoV-2 replication and transcription complex (RTC) structure. Based on these data, we have proposed a structural model of a Nsp9-RNA complex, shedding light on the molecular details of these important interactions., (© 2021 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.)

Extracellular vesicles (EVs) have been lauded as next-generation medicines, but very few EV-based therapeutics have progressed to clinical use. Limited clinical translation is largely due to technical barriers that hamper our ability to mass produce EVs, i.e., to isolate, purify, and characterize them effectively. Technical limitations in comprehensive characterization of EVs lead to unpredicted biological effects of EVs. Here, using a range of optical and non-optical techniques, we showed that the differences in molecular composition of EVs isolated using two isolation methods correlated with the differences in their biological function. Our results demonstrated that the isolation method determines the composition of isolated EVs at single and sub-population levels. Besides the composition, we measured for the first time the dry mass and predicted sedimentation of EVs. These parameters were likely to contribute to the biological and functional effects of EVs on single cell and cell cultures. We anticipate that our new multiscale characterization approach, which goes beyond traditional experimental methodology, will support fundamental understanding of EVs as well as elucidate the functional effects of EVs in in vitro and in vivo studies. Our findings and methodology will be pivotal for developing optimal isolation methods and establishing EVs as mainstream therapeutics and diagnostics. This innovative approach is applicable to a wide range of sectors including biopharma and biotechnology as well as to regulatory agencies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Phan, Divakarla, Yeo, Lei, Tharkar, Pansani, Leslie, Tong, Coleman, Jämting, Du Plessis, New, Kalionis, Demokritou, Woo, Cho and Chrzanowski.)

Single-stranded DNA-binding proteins (SSBs) are essential to all living organisms as protectors and guardians of the genome. Apart from the well-characterized RPA, humans have also evolved two further SSBs, termed hSSB1 and hSSB2. Over the last few years, we have used NMR spectroscopy to determine the molecular and structural details of both hSSBs and their interactions with DNA and RNA. Here we provide a detailed overview of how to express and purify recombinant versions of these important human proteins for the purpose of detailed structural analysis by high-resolution solution-state NMR.

Background: Among men with clinically low-risk prostate cancer, we have previously documented heterogeneity in terms of clinical characteristics and genomic risk scores., Objective: To further study the underlying tumor biology of this patient population, by interrogating broader patterns of gene expression among men with clinically low-risk tumors., Design, Setting, and Participants: Prostate biopsies from 427 patients considered potentially suitable for active surveillance underwent central pathology review and genome-wide expression profiling. These cases were compared with 1290 higher-risk biopsy cases with diverse clinical features from a prospective genomic registry., Outcome Measurements and Statistical Analysis: Average genomic risk (AGR) was determined from 18 published prognostic signatures, and MSigDB hallmark gene sets were analyzed using bootstrapped clustering methods. These sets were examined in relation to clinical variables and pathological and biochemical outcomes using multivariable regression analysis., Results and Limitations: A total of 408 (96%) biopsies passed RNA quality control. Based on AGR quartiles defined by the high-risk multicenter cases, the University of California, San Francisco (UCSF) low-risk patients were distributed across the quartiles as 219 (54%), 107 (26%), 61 (15%), and 21 (5%). Unsupervised clustering analysis of the hallmark gene set scores revealed three clusters, which were enriched for the previously described PAM50 luminal A, luminal B, and basal subtypes. AGR, but not the clusters, was associated with both pathological (odds ratio 1.34, 95% confidence interval [CI] 1.14-1.58) and biochemical outcomes (hazard ratio 1.53, 95% CI 1.19-1.93). These results may underestimate within-prostate genomic heterogeneity., Conclusions: Prostate cancers that are homogeneously low risk by traditional characteristics demonstrate substantial diversity at the level of genomic expression. Molecular substratification of low-risk prostate cancer will yield a better understanding of its divergent biology and, in the future may help personalize treatment recommendations., Patient Summary: We studied the genomic characteristics of tumors from men diagnosed with low-risk prostate cancer. We found three main subtypes of prostate cancer with divergent tumor biology, similar to what has previously been found in women with breast cancer. In addition, we found that genomic risk scores were associated with worse pathology findings and prostate-specific antigen recurrence after surgery. These results suggest even greater genomic diversity among low-risk patients than has previously been documented with more limited signatures., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: There is accumulating evidence for the role of fronto-striatal and associated circuits in obsessive-compulsive disorder (OCD) but limited and conflicting data on alterations in cortical thickness., Aims: To investigate alterations in cortical thickness and subcortical volume in OCD., Method: In total, 412 patients with OCD and 368 healthy adults underwent magnetic resonance imaging scans. Between-group analysis of covariance of cortical thickness and subcortical volumes was performed and regression analyses undertaken., Results: Significantly decreased cortical thickness was found in the OCD group compared with controls in the superior and inferior frontal, precentral, posterior cingulate, middle temporal, inferior parietal and precuneus gyri. There was also a group × age interaction in the parietal cortex, with increased thinning with age in the OCD group relative to controls., Conclusions: Our findings are partially consistent with earlier work, suggesting that group differences in grey matter volume and cortical thickness could relate to the same underlying pathology of OCD. They partially support a frontostriatal model of OCD, but also suggest that limbic, temporal and parietal regions play a role in the pathophysiology of the disorder. The group × age interaction effects may be the result of altered neuroplasticity., (© The Royal College of Psychiatrists 2017.)

Serotype 1 Streptococcus pneumoniae is a leading cause of invasive pneumococcal disease (IPD) worldwide, with the highest burden in developing countries. We report the whole-genome sequencing analysis of 448 serotype 1 isolates from 27 countries worldwide (including 11 in Africa). The global serotype 1 population shows a strong phylogeographic structure at the continental level, and within Africa there is further region-specific structure. Our results demonstrate that region-specific diversification within Africa has been driven by limited cross-region transfer events, genetic recombination and antimicrobial selective pressure. Clonal replacement of the dominant serotype 1 clones circulating within regions is uncommon; however, here we report on the accessory gene content that has contributed to a rare clonal replacement event of ST3081 with ST618 as the dominant cause of IPD in the Gambia.

Introduction: South Africa started routine infant immunization against Haemophilus influenzae serotype b (Hib) disease in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose. Following initial declines in Hib disease, national surveillance has identified increasing numbers of Hib disease episodes in fully vaccinated children., Materials and Methods: We reviewed national laboratory-based surveillance data from 2003 through 2009 for invasive Hib disease episodes among children <5 years, including HIV status and vaccination histories. We defined HibCV failures as invasive Hib disease in children at least four months of age who had received all recommended doses of HibCV., Results: Despite high HibCV vaccination coverage, detection rates of Hib disease in children <5 years increased from 0.7 per 100,000 population in 2003 to 1.3/100,000 in 2009 (p<0.001). Among 263 episodes of invasive Hib disease among children with known vaccination status, 135 (51%) were classified as vaccine failures. Of vaccine failures, 55% occurred among case patients ≥18 months old. HIV status was documented for 90 children with vaccine failure; 53% were not HIV infected., Discussion and Conclusions: Vaccine failures, which occurred in both HIV-infected and -uninfected children, comprised half of the rise in invasive Hib disease detected in South African children 10 years after national introduction of Hib vaccine. These findings suggest that HibCV recommendations may require revision. In November 2010, children in South Africa began receiving a booster dose of HibCV as part of a pentavalent vaccine., (Copyright © 2011 Elsevier Ltd. All rights reserved.)