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Introduction: PRP is gaining increasing interest for pain relief and improvement of joint function in patients with knee osteoarthritis (KOA) but practices and results remain heterogeneous limiting its adoption as standard of care. Current international recommendations are to collect real-life evidence of efficacy with a systematic monitoring of PRP quality and patients' outcomes. We aimed to analyze the response of patients presenting KOA and treated with standardized PRP injection in routine care. We also investigated the potential contributing factors including patient's phenotype and PRP characteristics. Methods: Patients with symptomatic KOA and that failed first-line therapy received a single injection of a qualified PRP prepared using medical devices allowing to recover a high/very high volume of very pure PRP. Visual analogue scale (VAS) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) score were recorded at baseline and during 18 months follow-up. Results: 431 patients had available follow-up data at 3 months, 291 at 6 months, 137 at 12 months and 44 at 18 months. PRP induced a significant decrease of WOMAC score at all follow up endpoints (29.2 ± 19.2 at 3 months, p

To assess the genetic characteristics of the early emerging SARS-CoV-2 Omicron variant strains, we retrospectively analyzed a collection of 150 nasopharyngeal samples taken from a series of outpatient cases tested positive by a referenced qRT-PCR assay during the reported period of Omicron variant emergence in December 2021, in northeastern region of France. Next Generation Sequencing (NGS) analysis of SARS-CoV-2 spike sequences revealed that only 3 (2 %) of these detected strains were Omicron variants, while 147 (98 %) were identified as previously described delta variants. Our phylogenetic analyzes of SARS-CoV-2 RNA genomes showed that these French early emerging Omicron variants may have originated from South Africa or India. In addition, whole viral genome sequences NGS comparison analyzes allowed us to identify an original and uncharacterized Y170W spike mutation that was weakly and transiently detected during the period of SARS-CoV-2 Omicron variant emergence in human populations. Molecular modeling and docking experiments indicated that this original mutated residue Y170W was neither directly involved in binding to the SARS-CoV-2 receptor ACE2 nor in interacting with known neutralizing antibody sites. However, this new mutation may be responsible for preventing the transition from the closed to the open Spike conformation, thus promoting the early emergence of the Omicron variant. Overall, these results underscore the epidemiological utility of a routine whole-genome viral NGS strategy that enables genotypic characterization of emerging or mutant SARS-CoV-2 variants, which could have significant implications for public health policy.

Sediment geochemistry is one lens through which lake sediments are studied to reconstruct local and regional environmental processes. The measurement of sediment elemental composition has historically relied on expensive and destructive methods that limit the spatial and temporal scale of study. Micro-X-ray fluorescence (µXRF) core scanning offers a non-destructive, high-resolution alternative, but its results (i.e., intensity expressed as counts per second) are considered semi-quantitative and comparison among sites requires calibration. Calibration methods are emerging, although they are not yet widely employed and require further assessment of their efficacy. Using 135 sediment samples from 48 lakes across Canada, we assessed the congruence between µXRF and conventionally measured element compositions with various normalization and calibration techniques. Normalization of µXRF data to common proxies (e.g., Ca, Si, Ti, coherence:incoherence ratio, and total counts per second) often improved correlations between µXRF and conventional data, but increases were modest and not consistent for all elements. Our results suggest that µXRF normalization techniques should be applied cautiously, as no proxy represents a “one-size-fits-all” solution. The performance of multivariate log-ratio calibration (MLC) was more consistent, yielding moderate to strong improvement of the correlations between reference and predicted element concentrations. Random forest regression models outperformed partial least squares regression models for almost all elements. MLC may be applied where knowledge of elemental concentration is of great importance, or when comparing across multiple sites with diverse sediment geochemistries. Overall, our results reinforce uncalibrated µXRF core scanning as a strong investigative tool for measuring sediment geochemistry. Although calibrated µXRF data shows promise, conventional methods for measuring sediment geochemistry are still necessary for comparing element concentrations with sediment quality guidelines.

Objective: To examine the feasibility, the criterion, and the construct convergent validity of the 2-Minute Walk Test (2MWT) and the 10-Meter Walk Test (10MeWT) against the 6-Minute Walk Test (6MWT) to assess walking capacity in people with cancer. The criterion concurrent validity of a self-test version of the 10MeWT (10MeWTself-test) was also evaluated against the 10MeWT. Methods: Fifty-six people with cancer performed the 2MWT, the 10MeWT at comfortable and fast speeds, the 6MWT, and the 10MeWTself-test. The feasibility of the tests was assessed using safety, adverse events, space requirements, time taken to administer and interpret the tool, equipment or training required, cost, and portability as criteria. Validity was assessed using Pearson correlation coefficients and Bland Altman plots. Results: The 2MWT, 6MWT, 10MeWT, and 10MeWTself-test were feasible for people with cancer. The 2MWT and the 10MeWT results were moderately to strongly correlated with the 6MWT results (0.61

Preterm birth disrupts important neurodevelopmental processes occurring from mid-fetal to term-age. Musicotherapy, by enriching infants’ sensory input, might enhance brain maturation during this critical period of activity-dependent plasticity. To study the impact of music on preterm infants’ brain structural changes, we recruited 54 very preterm infants randomized to receive or not a daily music intervention, that have undergone a longitudinal multi-shell diffusion MRI acquisition, before the intervention (at 33 weeks’ gestational age) and after it (at term-equivalent-age). Using whole-brain fixel-based (FBA) and NODDI analysis (n = 40), we showed a longitudinal increase of fiber cross-section (FC) and fiber density (FD) in all major cerebral white matter fibers. Regarding cortical grey matter, FD decreased while FC and orientation dispersion index (ODI) increased, reflecting intracortical multidirectional complexification and intracortical myelination. The music intervention resulted in a significantly higher longitudinal increase of FC and ODI in cortical paralimbic regions, namely the insulo-orbito-temporopolar complex, precuneus/posterior cingulate gyrus, as well as the auditory association cortex. Our results support a longitudinal early brain macro and microstructural maturation of white and cortical grey matter in preterm infants. The music intervention led to an increased intracortical complexity in regions important for socio-emotional development, known to be impaired in preterm infants.

Summary: Background: Pregnant individuals with coronavirus disease 2019 (COVID-19) are at increased risk of severe disease, prematurity, and stillbirth. In March 2021, vaccination for at risk pregnant women was recommended in Switzerland, expanding this to all pregnant women in May 2021. Our aim was to assess the safety of mRNA COVID-19 vaccines in pregnancy. Methods: This multicentre prospective cohort study describes early adverse events and perinatal outcomes in pregnant women who received at least one dose of mRNA vaccine between March 1st and December 27th, 2021 in Switzerland, using the COVI-PREG registry. Early adverse events were collected at least one month following vaccine administration. Pregnancy and neonatal outcomes were extracted from medical records using the maternity discharge letters providing follow-up information up to 5 days after birth. Findings: Of 1012 vaccinated women, 894 (88·3%) received both injections during pregnancy, with BNT162b2 (n = 271) or mRNA-1273 (n = 623) vaccines. Local events (mainly local pain) were reported in 81·3% and 80·5% after the first and second doses. Rates of systemic reactions (mainly fatigue and headache) were similar after the first dose and most frequent after the second dose of mRNA-1273. Of the 1012 women, four (0·4%; 95%CI [0·1-1·0]) severe early adverse events occurred: pulmonary embolism, preterm premature rupture of membranes, isolated fever with hospitalisation, and herpes zoster. Of 107 patients vaccinated before 14 weeks, one (0·9%; 95%CI [0·0-5·1]) early spontaneous abortions was reported (8 weeks). Of 228 vaccinated before 20 weeks one (0·4%; 95%CI [0·0-2·4]) late spontaneous abortion was reported (16 weeks). Of 513 women exposed before 37 weeks, 33 (6·4%; 95%CI [4·5-8·9]) delivered preterm. Among 530 patients exposed in pregnancy, no stillbirth was reported and 25 (4·7%; 95%CI [3·0-6·8]) neonates were admitted to intensive care unit. Interpretation: Frequent local and systemic effects were described after exposure to mRNA COVID-19 vaccines during pregnancy but severe events were rare. Women vaccinated during pregnancy did not experience higher adverse pregnancy or neonatal outcomes when compared to historical data on background risks in the obstetric population. Funding: This research was funded by a grant from the Swiss Federal Office of Public Health and the CHUV Foundation.

Summary: We present a protocol to generate an advanced ex vivo model of human placenta. We use a vibrating tissue slicer to obtain precision-cut slices representative of the entire thickness of human placenta. This approach delivers standardized cultures with a preserved microstructure and cellular composition comparable to the native tissue. We applied this system to study SARS-CoV-2 infection at the maternal-fetal interface. Moreover, this system can be used to investigate the basic functions of the human placenta in health and disease.For complete details on the use and execution of this protocol, please refer to Fahmi et al. (2021).

The cyclical structure of epilepsy was recently (re)-discovered through years-long intracranial electroencephalography (EEG) obtained with implanted devices. In this review, we discuss how new revelations from chronic EEG relate to the practice and interpretation of conventional EEG. We argue for an electrographic definition of seizures and highlight the caveats of counting epileptiform discharges in EEG recordings of short duration. Limitations of conventional EEG have practical implications with regard to titrating anti-seizure medications and allowing patients to drive, and we propose that chronic monitoring of brain activity could greatly improve epilepsy care. An impending paradigm shift in epilepsy will involve using next-generation devices for chronic EEG to leverage known biomarkers of disease state.

الملخص: أهداف البحث: تهدف هذه الدراسة للتحقق من قدرة البوابات الحسية السمعية لدى الحفاظ باستخدام فحص استجابة جذع الدماغ السمعي مع أو بدون المهام النفسية. طرق البحث: تم اشراك ٢٣ مشاركا في هذه الدراسة. منهم ١١ من الحفاظ الذين يحفظون ٣٠ جزءا من القرآن الكريم و١٢ من غير الحفاظ كمجموعة التحكم. كان لجميع المشاركين إدراك سمع طبيعي وتم إخضاعهم لفحص استجابة جذع الدماغ السمعي مع أو بدون المهام النفسية. تمت استجابة جذع الدماغ السمعي عند ٧٠ ديسيبل باستخدام ٣٠٠٠ هرتز نغمة تحفيز اندفاعية مع ٢-٠-٢ دورة بمعدل تكرار للتحفيز ٤٠ هرتز. كما تم قياس إشارة استجابة جذع الدماغ السمعي سعة ٥ واختفائها ومقارنتها إحصائيا. تم عمل اختبار المدى الرقمي الأمامي لتحديد سعة الذاكرة العاملة للمشاركين. النتائج: لم يوجد اختلاف كبير في إشارة استجابة جذع الدماغ السمعي سعة ٥ واختفائها بين الحفاظ وغير الحفاظ في استجابة جذع الدماغ السمعي مع أو بدون المهام النفسية. لم يكن هناك أيضا فرق كبير في إشارة استجابة جذع الدماغ السمعي سعة ٥ واختفائها عند المجموعتين مع أو بدون المهام النفسية. بالإضافة لذلك، لم يلاحظ هناك اختلاف كبير في المدى الرقمي لدرجة الذاكرة العاملة بين المجموعتين. الاستنتاجات: في هذه الدراسة، اعتمادا على نتائج استجابة جذع الدماغ السمعي، أظهر الحفاظ نفس سعة البوابات الحسية السمعية مثل مجموعة غير الحفاظ. وكانت نتائج استجابة جذع الدماغ السمعي متسقة مع المدى الرقمي لدرجة اختبار الذاكرة العاملة. يعني هذا أن لدى المجموعتين أداء ذاكرة عمل متماثلة. ومع ذلك، النتائج محدودة فقط لطرق التقييم المحددة المستخدمة في هذه الدراسة. Abstract: Objective: This study aims to investigate the auditory sensory gating capacity in Huffaz using an auditory brainstem response (ABR) test with and without psychological tasks. Methods: Twenty-three participants were recruited for this study. The participants were comprised of 11 Huffaz who memorized 30 chapters of the Islamic Scripture (from the Quran) and 12 non-Huffaz as the control group. All participants had normal hearing perception and underwent an ABR test with and without psychological tasks. The ABR was elicited at 70 dB nHL using a 3000 Hz tone burst stimulus with a 2-0-2 cycle at a stimulus repetition rate of 40 Hz. The ABR wave V amplitude and latencies were measured and statistically compared. A forward digit span test was also conducted to determine participants’ working memory capacity. Results: There were no significant differences in the ABR wave V amplitudes and latencies between Huffaz and non-Huffaz in ABR with and without psychological tasks. There were also no significant differences in the ABR wave V amplitudes and latencies in both groups of ABR with and without psychological tasks. In addition, no significant differences were identified in the digit span working memory score between both groups. Conclusions: In this study, based on the ABR findings, Huffaz showed the same auditory sensory gating capacity as the non-Huffaz group. The ABR result was consistent with the digit span working memory test score. This finding implies that both groups have similar working memory performance. However, the conclusion is limited to the specific assessment method that we used in this study.

The extracellular matrix is a complex three-dimensional network of molecules that provides cells with a complex microenvironment. The major constituents of the extracellular matrix such as collagen, elastin and associated proteins form supramolecular assemblies contributing to its physicochemical properties and organization. The structure of proteins and their supramolecular assemblies such as fibrils have been studied at the atomic level (e.g., by X-ray crystallography, Nuclear Magnetic Resonance and cryo-Electron Microscopy) or at the microscopic scale. However, many protein complexes are too large to be studied at the atomic level and too small to be studied by microscopy. Most extracellular matrix components fall into this intermediate scale, so-called the mesoscopic scale, preventing their detailed characterization. Simulation and modelling are some of the few powerful and promising approaches that can deepen our understanding of mesoscale systems. We have developed a set of modelling tools to study the self-organization of the extracellular matrix and large motion of macromolecules at the mesoscale level by taking advantage of the dynamics of articulated rigid bodies as a mean to study a larger range of motions at the cost of atomic resolution.

Before the arrival of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators women with CF and impaired lung function were experiencing a high risk of complications and mortality during and the years after pregnancy. The arrival of the highly efficient CFTR modulator, Elexacaftor-Tezacaftor-Ivacaftor (ETI) resulted in an improvement of lung function, quality of life and fertility. Here we report a case of successful pregnancy and uncomplicated delivery for a CF patient with severely impaired lung function receiving ETI prior to conception.

Background: Translational research refers to scientific findings that have been extensively studied in models and find their way to clinical studies. In a certain sense in translational anatomy a similar application of conventional anatomical knowledge finds its way to clinics in the surgical theatre. With the propagation of endoscopic middle ear surgery there has been a renewed interest in many early anatomical terms, even many years after their discovery, which may threaten the correct and classic eponyms. Moreover, the application of robotic ear surgery executing minimal invasive keyhole accesses requires translation of anatomical knowledge to the sub-millimetric level. Purpose: This review reports relevant anatomy of the temporal bone for robotic cochlear implantation reflecting also on recent revisions of terminology. Results: In 2019, the Terminologia Neuroanatomica (TNA 2017) was accepted at the 19th World Congress of the International Federation of Associations of Anatomists (IFAA) in London as its official terminology for the central and peripheral nervous system and the sense organs. This review follows the terminology of in the TNA, but also compares anatomical and clinical terms to bridge the gap between both approaches, and provides brief descriptions and illustrations of relevant structures for robotic cochlear implantation and elaborates on their significance. With the emergence and more widespread use of the endoscopic ear surgery and image guided ear surgery, visualization of certain anatomical structures has improved. Coinciding, there has been a renewed interest in many early anatomical terms, even many years after their discovery, which may threaten the correct and classic eponyms. Conclusions: Consequently, this review also presents an overview of eponyms associated with specific structures over the years. In Supplementary Tables, the changes in terminology are reported.

Multiple stressors affect water quality and biodiversity in lakes worldwide. However, our understanding of which combinations of stressors are of greatest impact and how lakes have shifted from their pre-industrial baselines is fragmented. Questions remain regarding how multiple trophic groups are affected by global change stressors and whether region-specific differences need to be considered. Here, we apply multiple factor analyses together with latent variable modeling to quantify potential interactions within and among taxa that span multiple trophic levels (i.e. diatoms, cladocerans and chironomids) to improve our understanding of paleo-environmental dynamics from a suite of Canadian lakes spanning four ecozones: the Boreal Shield, the Mixedwood Plains, the Atlantic Highlands, and the Atlantic Maritimes. Across all ecozones, multi-trophic assemblages were distinguished in a multiple factor analysis along a land-use gradient, with mesotrophic/eutrophic diatoms and profundal chironomids tolerant of low bottom-water oxygen concentrations recorded in more disturbed sites. Functional units across three indicator groups formed distinct networks of co-responses to key environmental and land-use gradients, although cladocerans seemed to be driven by additional (i.e., residual) gradients. Applying a temporal beta-diversity approach between modern and pre-industrial assemblages, we detected significantly greater turnover of diatom functional groups in high versus low human impact sites (p = 0.03, n = 57), with similar but non-significant trends apparent with the chironomid and cladoceran groups. Ecozonal differences in temporal turnover were also evident in diatom (p = 0.003, n = 57) and chironomid functional groups (p = 0.04, n = 41). The ecozonal differences may be partially due to differential sensitivities of the pre-industrial assemblages and may also be driven by historical disturbances. Our work highlights how the magnitude and direction of ecological change vary across ecozones and can modify responses to human impacts, with a general trend of higher species turnover in sites with greater human disturbance.

Background: In obese patients, preoxygenation with non-invasive ventilation (NIV) was reported to improve outcomes compared with facemask. In this setting, high-flow nasal cannulae (HFNC) used before and during intubation has never been studied against NIV. Methods: The PREOPTIPOP study is a randomised, single-centre, open-labelled, controlled trial including obese patients requiring intubation before scheduled surgery. Patients were randomised to receive preoxygenation by HFNC or NIV. HFNC was maintained throughout intubation whereas NIV was removed when apnea occurred to perform laryngoscopy. The study was designed to assess the superiority of HNFC. The primary outcome was the lowest level of end-tidal oxygen concentration (EtO2) within 2 min after intubation. Secondary outcomes included drop in pulse oximetry and complications related to intubation. Main findings: A total of 100 patients were randomised. The intent-to-treat analysis found median [IQR] lowest EtO2 of 76% [66–82] for HFNC and 88% [82–90] for NIV (mean difference − 12·1 [−15·1 to −8·5], p

Infertility is a disease that affects one in seven couples. As male infertility affects approximately 30% of these couples with an unknown cause in half the cases, it represents a major public health concern. The classic treatment of male infertility involves intrauterine insemination, with modest outcome, and in vitro fertilization with intracytoplasmic sperm injection, which is known to be invasive and expensive, without treating the specific cause of infertility. Male fertility is mainly evaluated through a semen assessment where abnormal parameters such as concentration and motility can be associated with a decreased chance of conception. Infectious processes represent plausible candidates for male infertility. Chlamydia trachomatis is well known to cause female infertility through tubal damage but its role in male infertility remains controversial. The link between ureaplasmas/mycoplasmas and male infertility is also debatable. The potential negative impact of these bacteria on male fertility might not only involve semen parameters but also, as with C. trachomatis, include important physiological mechanisms such as fertilization processes that are not routinely assessed during infertility investigation. Basic research is important to help determine the exact effect of these bacteria on male fertility to develop targeted treatment and go beyond in vitro fertilization with intracytoplasmic sperm injection. Keywords: Chlamydia, male infertility, Mycoplasma, Ureaplasma

Summary: Reproducibility in molecular and cellular studies is fundamental to scientific discovery. To establish the reproducibility of a well-defined long-term neuronal differentiation protocol, we repeated the cellular and molecular comparison of the same two iPSC lines across five distinct laboratories. Despite uncovering acceptable variability within individual laboratories, we detect poor cross-site reproducibility of the differential gene expression signature between these two lines. Factor analysis identifies the laboratory as the largest source of variation along with several variation-inflating confounders such as passaging effects and progenitor storage. Single-cell transcriptomics shows substantial cellular heterogeneity underlying inter-laboratory variability and being responsible for biases in differential gene expression inference. Factor analysis-based normalization of the combined dataset can remove the nuisance technical effects, enabling the execution of robust hypothesis-generating studies. Our study shows that multi-center collaborations can expose systematic biases and identify critical factors to be standardized when publishing novel protocols, contributing to increased cross-site reproducibility. : In this article, Lakics and colleagues show that, while individual laboratories are able to identify consistent molecular and seemingly statistically robust differences between iPSC neuronal models, cross-site reproducibility is poor. Their findings support multi-center collaborations to expose systematic biases and identify critical factors to be standardized to improve reproducibility in iPSC-based molecular experiments. Keywords: induced pluripotent stem cell, reproducibility, cross-site experimental variation, cortical neurons, gene expression profile, proteomic profiles, single-cell sequencing, molecular profiling, stembancc, public-private partnership

Abnormal variations of the neonatal brain perfusion can result in long-term neurodevelopmental consequences and cerebral perfusion imaging can play an important role in diagnostic and therapeutic decision-making. To identify at-risk situations, perfusion imaging of the neonatal brain must accurately evaluate both regional and global perfusion. To date, neonatal cerebral perfusion assessment remains challenging. The available modalities such as magnetic resonance imaging (MRI), ultrasound imaging, computed tomography (CT), near-infrared spectroscopy or nuclear imaging have multiple compromises and limitations. Several promising methods are being developed to achieve better diagnostic accuracy and higher robustness, in particular using advanced MRI and ultrasound techniques.The objective of this state-of-the-art review is to analyze the methodology and challenges of neonatal brain perfusion imaging, to describe the currently available modalities, and to outline future perspectives.

Background: Multiple factors contribute to the etiology of addiction, including genetics, sex, and a number of addiction-related behavioral traits. One behavioral trait where individuals assign incentive salience to food stimuli (“sign-trackers”, ST) are more impulsive compared to those that do not (“goal-trackers”, GT), as well as more sensitive to drugs and drug stimuli. Furthermore, this GT/ST phenotype predicts differences in other behavioral measures. Recent studies have implicated the gut microbiota as a key regulator of brain and behavior, and have shown that many microbiota-associated changes occur in a sex-dependent manner. However, few studies have examined how the microbiome might influence addiction-related behaviors. To this end, we sought to determine if gut microbiome composition was correlated with addiction-related behaviors determined by the GT/ST phenotype. Methods: Outbred male (N=101) and female (N=101) heterogeneous stock rats underwent a series of behavioral tests measuring impulsivity, attention, reward-learning, incentive salience, and locomotor response. Cecal microbiome composition was estimated using 16S rRNA gene amplicon sequencing. Behavior and microbiome were characterized and correlated with behavioral phenotypes. Robust sex differences were observed in both behavior and microbiome; further analyses were conducted within sex using the pre-established goal/sign-tracking (GT/ST) phenotype and partial least squares differential analysis (PLS-DA) clustered behavioral phenotype. Results: Overall microbiome composition was not associated to the GT/ST phenotype. However, microbial alpha diversity was significantly decreased in female STs. On the other hand, a measure of impulsivity had many significant correlations to microbiome in both males and females. Several measures of impulsivity were correlated with the genus Barnesiella in females. Female STs had notable correlations between microbiome and attentional deficient. In both males and females, many measures were correlated with the bacterial families Ruminocococcaceae and Lachnospiraceae. Conclusions: These data demonstrate correlations between several addiction-related behaviors and the microbiome specific to sex.

The intracellular bacterium Waddlia chondrophila, which belongs to the Chlamydiales order, was found to be associated with miscarriage in humans. There is little to no knowledge regarding the mode of infection, impact on the neonate and pathophysiology of this emerging bacterium. We have previously shown that W. chondrophila induces a systemic infection, organ pathology and elicits T helper type 1-associated humoral immunity in a murine model of genital infection. In the present study, we took advantage of this model of infection to evaluate the impact of this bacterium on the mouse pregnancy. We used two routes of inoculation, vaginal and intrauterine, to introduce infection before and after mating. Our results show that genital infection by W. chondrophila did not have any significant impact on gestation length and maternal weight gain, nor on the number of offspring and their weight. This observation indicates that the mouse model of infection is not suitable to study the effect of W. chondrophila on pregnancy and alternative models of infection, including in vitro ones, should be used. Moreover, an indirect immunopathological mechanism activated by this bacterium should be further explored. Keywords: Adverse pregnancy outcomes, chlamydiales, genital model, mouse, Waddlia chondrophila

Study region: The Bromo-Tengger volcanic aquifer system, (East Java, Indonesia). Study focus: Andesitic volcanic aquifers in Indonesia are an important source of groundwater supply for the population. The artesian flow from high discharge springs facilitates the access for irrigation and drinking water but continuously flowing artesian wells exert an increasing pressure on the groundwater resource. Given the complexity of the volcanic edifice, a multidisciplinary approach including geological, hydrometeorological, hydrochemical and isotopic measurements was performed to characterise the hydrogeological functioning of the volcano’s northern flank. New hydrogeological insights for the region: Two main hydrogeological systems are identified: a system with perched aquifers in the lava flows and pyroclastic complex, supplying low discharge springs or infiltrating to a deep flow system. The latter system is unconfined and provides groundwater to the downstream plain that hosts a confined multi-layer volcano-sedimentary aquifer. The joint implementation of a quantitative isotopic approach and a groundwater budget allows characterising aquifer recharge along the whole volcano flank. It is mainly controlled by the rainfall distribution that peaks around 1200 m elevation. The caldera basin on the top of the volcano has a very limited contribution to recharge. A conceptual hydrogeological model is proposed and compared to the main concepts of volcanic islands. This study is a first step for further scientific and management discussions to implement protection policies on the Bromo-Tengger aquifer system. Keywords: Hydrogeology, Volcanic aquifer, Andesite, Recharge, Isotopes, Hydrochemistry, Quantitative analysis

Waddlia chondrophila and Simkania negevensis are emerging Chlamydia-related bacteria. Similar to the pathogenic organisms Chlamydia pneumoniae and Chlamydia trachomatis, these emerging bacteria are implicated in human genital infections and respiratory diseases. We used a screening strategy based on a newly developed S. negevensis–specific quantitative real-time PCR (qPCR) and a pan-Chlamydiales qPCR. We could not detect S. negevensis in 458 respiratory, genitourinary, cardiac and hepatic samples tested. One urethral swab was positive for W. chondrophila. We observed a low prevalence of Chlamydiales in respiratory samples (1/200, 0.5%), which suggests that C. pneumoniae is an uncommon respiratory pathogen. Furthermore, we screened 414 human serum samples from Switzerland, England and Israel and observed a low prevalence (

Perinatal arterial stroke is the most frequent form of cerebral infarction in children. Neonatal seizures are the most frequent symptom during the neonatal period. The current management of perinatal stroke is based on supportive care. It is currently unknown if treatment of the seizures modifies the outcome, and no clinical studies have focused on seizures during neonatal stroke. We studied the effect of phenobarbital and levetiracetam on an ischemic-reperfusion stroke model in P7 rats using prolonged electroencephalographic recordings and a histologic analysis of the brain (24 h after injury). The following two types of epileptic events were observed: 1) bursts of high amplitude spikes during ischemia and the first hours of reperfusion and 2) organized seizures consisting in discharges of a 1–2 Hz spike-and-wave. Both phenobarbital and levetiracetam decreased the total duration of the bursts of high amplitude spikes. Phenobarbital also delayed the start of seizures without changing the total duration of epileptic discharges. The markedly limited efficacy of the antiepileptic drugs studied in our neonatal stroke rat model is frequently observed in human neonatal seizures. Both drugs did not modify the stroke volume, which suggests that the modification of the quantity of bursts of high amplitude spikes does not influence the infarct size. In the absence of a reduction in seizure burden by the antiepileptic drugs, we increased the seizure burden and stroke volume by combining our neonatal stroke model with a lithium-pilocarpine-induced status epilepticus. Our data suggest that the reduction of burst of spikes did not influence the stroke volume. The presence of organized seizure with a pattern close to what is observed in human newborns seems related to the presence of the infarct. Further research is required to determine the relationship between seizure burden and infarct volume.

Waddlia chondrophila and Chlamydia trachomatis are intracellular bacteria associated with human miscarriage. We investigated their role in human preterm birth. Whereas presence of Chlamydia trachomatis DNA in genital tract was associated with human preterm birth, Waddlia was not, despite being present in women's genital tracts.

Waddlia chondrophila, an obligate intracellular bacterium of the Chlamydiales order, is considered as an agent of bovine abortion and a likely cause of miscarriage in humans. Its role in respiratory diseases was questioned after the detection of its DNA in clinical samples taken from patients suffering from pneumonia or bronchiolitis. To better define the role of Waddlia in both miscarriage and pneumonia, a tool allowing large-scale serological investigations of Waddlia seropositivity is needed. Therefore, enriched outer membrane proteins of W. chondrophila were used as antigens to develop a specific ELISA. After thorough analytical optimization, the ELISA was validated by comparison with micro-immunofluorescence and it showed a sensitivity above 85% with 100% specificity. The ELISA was subsequently applied to human sera to specify the role of W. chondrophila in pneumonia. Overall, 3.6% of children showed antibody reactivity against W. chondrophila but no significant difference was observed between children with and without pneumonia. Proteomic analyses were then performed using mass spectrometry, highlighting members of the outer membrane protein family as the dominant proteins. The major Waddlia putative immunogenic proteins were identified by immunoblot using positive and negative human sera. The new ELISA represents an efficient tool with high throughput applications. Although no association with pneumonia and Waddlia seropositivity was observed, this ELISA could be used to specify the role of W. chondrophila in miscarriage and in other diseases.

The role for growth restriction in the multifactorial pathophysiology of developing white-matter damage remains debated. We studied rat pups with prenatal growth restriction (GR) induced by unilateral ligation of the uterine artery. Pups with severe GR exhibited white-matter damage that persisted to adulthood [Olivier, P., Baud, O., Evrard, P., Gressens, P.,Verney, C., 2005. Prenatal ischemia and white matter damage in rats. J. Neuropathol. Exp. Neurol. 64, 998–1006]. Moderate GR was associated with diffuse white-matter lesions, microglial activation, and astrogliosis. Loss of pre-oligodendrocytes on postnatal day 7 was followed by a delay in myelination. Following a cortical excitotoxic insult on postnatal day 5, the size of the induced white-matter lesion was smaller in pups with moderate GR and larger in pups with severe GR, compared to normal pups. The increased pre-oligodendrocyte proliferation seen in the white matter of pups with moderate GR subjected to this “double-hit” injury may constitute a heretofore-undescribed neuroprotective mechanism of immature white matter.

Brain lesions induced in newborn mice by the glutamatergic agonists ibotenate (acting on NMDA and metabotropic receptors) and S-bromowillardiine (acting on AMPA-kainate receptors) mimic some aspects of white matter cysts and transcortical necrosis observed in human perinatal brain damage. Topiramate (TPM), already used in children to manage newly diagnosed and refractory epilepsy, has potential neuroprotective effects that may be useful in human perinatal brain lesions. In the excitotoxic newborn mouse model, TPM provided dose-dependent and long-lasting protection of developing white matter and cortical plate against S-bromowillardiine. TPM had no significant effect on ibotenate-induced brain lesions. TPM-induced neuroprotection potentially involved increased survival of pre-oligodendrocytes, decreased neuronal apoptosis, inhibition of microglial activation and astrogliosis, and decreased seizure activity. Diazepam, phenytoin, and carbamazepine had no neuroprotective effect in this model. The present study provides experimental support for the consideration of TPM as a candidate therapy for excitotoxic perinatal brain lesions.

Attention deficit hyperactivity disorder (ADHD) is accompanied by resting-state alterations, including abnormal activity, connectivity and asymmetry of the default-mode network (DMN). Concurrently, recent studies suggested a link between ADHD and the presence of polymorphisms within the gene BAIAP2 (i.e., brain-specific angiogenesis inhibitor 1-associated protein 2), known to be differentially expressed in brain hemispheres. The clinical and neuroimaging correlates of this polymorphism are still unknown. We investigated the association between BAIAP2 polymorphisms and DMN functional connectivity (FC) asymmetry as well as behavioral measures in ADHD adults. Resting-state fMRI was acquired from 30 ADHD and 15 healthy adults. For each subject, rs7210438 and rs8079626 within the gene BAIAP2 were genotyped. ADHD severity, impulsiveness and anger were assessed for the ADHD group. Using multivariate analysis of variance, we found that genetic features do have an impact on DMN FC asymmetry. In particular, polymorphism rs8079626 affects medial frontal gyrus and inferior parietal lobule connectivity asymmetry, lower for AA than AG/GG carriers. Further, when combining FC asymmetry and the presence of the rs8079626 variant, we successfully predicted increased externalization of anger in ADHD. In conclusion, a complex interplay between genetic vulnerability and inter-hemispherical DMN FC asymmetry plays a role in emotion regulation in adult ADHD., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

With fractured rocks making up an important part of hydrocarbon reservoirs worldwide, detailed analysis of fractures and fracture networks is essential. However, common analyses on drill core and plug samples taken from such reservoirs (including hand specimen analysis, thin section analysis and laboratory porosity and permeability determination) however suffer from various problems, such as having a limited resolution, providing only 2D and no internal structure information, being destructive on the samples and/or not being representative for full fracture networks. In this paper, we therefore explore the use of an additional method - non-destructive 3D X-ray micro-Computed Tomography (μCT) - to obtain more information on such fractured samples. Seven plug-sized samples were selected from narrowly fractured rocks of the Hauptdolomit formation, taken from wellbores in the Vienna basin, Austria. These samples span a range of different fault rocks in a fault zone interpretation, from damage zone to fault core. We process the 3D μCT data in this study by a Hessian-based fracture filtering routine and can successfully extract porosity, fracture aperture, fracture density and fracture orientations - in bulk as well as locally. Additionally, thin sections made from selected plug samples provide 2D information with a much higher detail than the μCT data. Finally, gas- and water permeability measurements under confining pressure provide an important link (at least in order of magnitude) towards more realistic reservoir conditions. This study shows that 3D μCT can be applied efficiently on plug-sized samples of naturally fractured rocks, and that although there are limitations, several important parameters can be extracted. μCT can therefore be a useful addition to studies on such reservoir rocks, and provide valuable input for modelling and simulations. Also permeability experiments under confining pressure provide important additional insights. Combining these and other methods can therefore be a powerful approach in microstructural analysis of reservoir rocks, especially when applying the concepts that we present (on a small set of samples) in a larger study, in an automated and standardised manner.

Background: It was recently reported that a rare functional variant, R441H, in the human tryptophan hydroxylase-2 gene (hTPH2) could represent an important risk factor for unipolar major depression (UP) since it was originally found in 10% of UP patients (vs. 1.4% in control subjects)., Methods: We explored the occurrence of this variation in patients with affective disorders (n = 646), autism spectrum disorders (n = 224), and obsessive-compulsive disorder (OCD) (n = 201); in healthy volunteers with no psychiatric disorders (n = 246); and in an ethnic panel of control individuals from North Africa, Sub-Saharan Africa, India, China, and Sweden (n = 277)., Results: Surprisingly, we did not observe the R441H variant in any of the individuals screened (3188 independent chromosomes)., Conclusions: Our results do not confirm the role of the R441H mutation of the hTPH2 gene in the susceptibility to UP. The absence of the variant from a large cohort of psychiatric patients and control subjects suggests that the findings reported in the original study could be due to a genotyping error or to stratification of the initial population reported. Additional data by other groups should contribute to the clarification of the discrepancy between our results and those previous published.

Introduction: It is well known that polyneuropathy is associated with monoclonal IgM kappa., Exegesis: We report the case of a 79-year-old man with lymphoma and motor neuron disease at cervical level simulating amyotrophic lateral sclerosis (ALS). Neurological deficit with inflammatory process evolved within 4 months. Electrophysiological findings showed increased and enlarged muscular potentials with neurogenic patterns. Nerve conduction velocities were normal, with neither multifocal neuropathy nor persistent conduction blocks. Besides mixed cryoglobulinemia type II, antisulfatide antibodies issued from monoclonal IgM were found. They were directed against myelin glycosphingolipids. No antiganglioside GM1 antibodies could be detected. This not only evoked ALS but also proximal motor axonopathy related with monoclonal IgM., Conclusions: This case suggests that antisulfatide antibodies often present in sensitive demyelinating polyneuropathy could also be involved in lower motor neuron syndrome.

In an acute, double-blind placebo-controlled study, three groups of nine healthy subjects were included. Each group received, in randomized and weekly intervals, a single oral dose of dexfenfluramine (15 mg, 30 mg or 60 mg) or placebo. Psychometric and EEG studies were carried out before as well as 1, 2, 3, 4, 5 and 6 h after drug administration. Changes from predrug to postdrug conditions for each time were determined by the ratio of absolute spectral power and compared to the evolution of power spectra under placebo conditions. Statistical evaluation was done with ANOVA. Dexfenfluramine induced a dose-dependent decrease of power spectra for theta and alpha 1 bands and an increase for the beta band. Topographic brain mapping of these significant changes displayed a central and posterior decrease for theta and alpha 1 bands, and a temporal localization for the beta-power. Maps of relative power-enhanced changes were seen in absolute power and provided false displays. Psychometric evaluation of dexfenfluramine effects only showed trends to extraversion and increased mood scores but no statistical significance was found. Arousal and performance tests were unchanged. These results suggest that qEEG variations are more sensitive to serotonergic drug effects than psychometric investigations. It appears that spontaneous EEG power spectra variations with time must be accounted for by drug evaluation. Absolute power variations are more reliable than relative power. Methodological implications are discussed.