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Bartonella quintana infection can cause severe disease that includes clinical manifestations such as endocarditis, chronic bacteremia, and vasoproliferative lesions of the skin and viscera. B. quintana bacteria is transmitted by the human body louse (Pediculus humanus corporis) and is associated with homelessness and limited access to hygienic services. We report B. quintana infection in 2 kidney transplant recipients in the United States from an organ donor who was experiencing homelessness. One infection manifested atypically, and the other was minimally symptomatic; with rapid detection, both recipients received timely treatment and recovered. B. quintana was identified retrospectively in an archived donor hematoma specimen, confirming the transmission link. Information about the organ donor’s housing status was critical to this investigation. Evaluation for B. quintana infection should be considered for solid organ transplant recipients who receive organs from donors with a history of homelessness or of body lice infestation.

Bartonella quintana infection can lead to bacillary angiomatosis, peliosis hepatis, chronic bacteremia, and culture-negative endocarditis. Transmitted by the human body louse (Pediculus humanus humanus), B. quintana infection has become an emerging disease in recent decades among persons experiencing homelessness. By using retrospective laboratory surveillance, we identified 5 cases of left-sided, culture-negative B. quintana endocarditis among persons in New York, New York, USA, during January 1, 2020–November 23, 2023. Identifications were made by using molecular assays. All patients experienced unsheltered homelessness in the year before hospitalization. Of those patients, 4 experienced heart failure, 3 renal failure, and 2 embolic strokes; 2 died. Aortic valve replacement occurred in 4 cases. A history of possible body louse infestation was found in 4 cases. Clinicians should consider housing status and history of lice exposure in patients with suspected bartonellosis and have a low threshold for diagnostic testing and empiric treatment in patients experiencing homelessness.

Abstract Background We have previously found that almost two thirds (64.6%) of adults in Peru have an active headache disorder. Here, using data from the same sample, we present attributed burden at individual and population levels. We use these data to assess need for headache-related health care among this population. Methods We used the standard methodology of the Global Campaign against Headache. Cluster-sampling from five geographical regions of Peru (Cajamarca, Lima, Piura, Puno, San Martín) generated a sample representative of the population aged 18–65 years. At unannounced visits to households, we interviewed one adult from each using the HARDSHIP questionnaire. We assessed symptom burden in terms of headache frequency and usual duration and intensity, and impaired participation in paid work, household work and social or leisure activities using the HALT index. To assess need for health care, we counted all those with headache on ≥ 15 days/month (H15+), those with migraine on ≥ 3 days/month, and those with migraine or tension-type headache meeting either of two criteria: a) proportion of time in ictal state (pTIS) > 3.3% and intensity ≥ 2 (moderate-to-severe); b) ≥ 3 lost days from paid and/or household work during the preceding 3 months. We derived population-level estimates by factoring in prevalences. Results The sample size was N = 2,149. From individual data, we estimated population-level pTIS at 1.9–2.5%, this proportion of all time among adults in Peru being spent with headache, with migraine the greatest contributor (1.2%). At population level, headache was responsible for 0.5 days lost from paid work and 1.0 days from household work per person per 3 months, with migraine again the biggest contributor (0.2 and 0.5 days). However, at individual level, H15 + was associated with greatest burden (pTIS 14.9–24.9%; 2.3–4.5 lost workdays/3 months). A quarter of the sample (n = 590; 27.5%) fulfilled one or more of our health-care need criteria. Conclusion Headache disorders are responsible for high levels of ill health and economic burden in Peru, with a substantial requirement for health care. Health and economic policies balancing health benefits against the cost of providing care should take account of the productivity losses that might be recovered, and the expected cost-offset.

Abstract To examine the morphological impact of deep learning (DL)-quantified biomarkers on point-wise sensitivity (PWS) using microperimetry (MP) and optical coherence tomography (OCT) in intermediate AMD (iAMD). Patients with iAMD were examined by OCT (Spectralis). DL-based algorithms quantified ellipsoid zone (EZ)-thickness, hyperreflective foci (HRF) and drusen volume. Outer nuclear layer (ONL)-thickness and subretinal drusenoid deposits (SDD) were quantified by human experts. All patients completed four MP examinations using an identical custom 45 stimuli grid on MP-3 (NIDEK) and MAIA (CenterVue). MP stimuli were co-registered with corresponding OCT using image registration algorithms. Multivariable mixed-effect models were calculated. 3.600 PWS from 20 eyes of 20 patients were analyzed. Decreased EZ thickness, decreased ONL thickness, increased HRF and increased drusen volume had a significant negative effect on PWS (all p

Abstract Our study develops a generative adversarial network (GAN)-based method that generates faithful synthetic image data of human cardiomyocytes at varying stages in their maturation process, as a tool to significantly enhance the classification accuracy of cells and ultimately assist the throughput of computational analysis of cellular structure and functions. Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) were cultured on micropatterned collagen coated hydrogels of physiological stiffnesses to facilitate maturation and optical measurements were performed for their structural and functional analyses. Control groups were cultured on collagen coated glass well plates. These image recordings were used as the real data to train the GAN model. The results show the GAN approach is able to replicate true features from the real data, and inclusion of such synthetic data significantly improves the classification accuracy compared to usage of only real experimental data that is often limited in scale and diversity. The proposed model outperformed four conventional machine learning algorithms with respect to improved data generalization ability and data classification by incorporating synthetic data. This work demonstrates the importance of integrating synthetic data in situations where there are limited sample sizes and thus, effectively addresses the challenges imposed by data availability.

Abstract Lipoprotein (a) [Lp(a)] is suspected to have antifibrinolytic effects, however, its relevance for the severity of venous thromboembolic events remains unclear. We studied the association of Lp(a) levels with thrombus load in pulmonary embolism (PE). 90 patients (40% female, median age 70 [56–79] years) at our tertiary care hospital with a diagnosis of acute PE, available Lp(a) levels and CT pulmonary angiography (CT-PA) performed between April 2017 and December 2019 were included. All CT-PA scans were reanalyzed and thrombus load was determined via Qanadli CT obstruction index (CTOI) and most proximal thrombus location. Median Lp(a) levels were 11.4 [9.3–29.1] mg/dL, median D-dimer levels were 4.6 [2.1–9.8] mg/L, median CTOI was 23 [8–50], central PE was present in 27 (30%) patients. Lp(a) did not correlate with CTOI (r = 0.02, p = 0.922) and was not associated with thrombus location (p = 0.369). CTOI significantly correlated with D-dimer (r = 0.43, p

Abstract Background The Brazilian Policy for Comprehensive Care for People with Rare Diseases was implemented in 2014; however, national epidemiological data on rare diseases (RDs) are scarce and mainly focused on specific disorders. To address this gap, University Hospitals, Reference Services for Neonatal Screening, and Reference Services for Rare Diseases, all of which are public health institutions, established the Brazilian Rare Diseases Network (RARAS) in 2020. The objective of this study was to perform a comprehensive nationwide epidemiological investigation of individuals with RDs in Brazil. This retrospective survey collected data from patients receiving care in 34 healthcare facilities affiliated with RARAS in 2018 and 2019. Results The survey included 12,530 participants with a median age of 15.0 years, with women representing 50.5% of the cohort. Classification according to skin color demonstrated that 5044 (47.4%) participants were admixed. Most had a confirmed diagnosis (63.2%), with a predominance of phenylketonuria (PKU), cystic fibrosis (CF), and acromegaly. Common clinical manifestations included global developmental delay and seizures. The average duration of the diagnostic odyssey was 5.4 years (± 7.9 years). Among the confirmed diagnoses, 52.2% were etiological (biochemical: 42.5%; molecular: 30.9%), while 47.8% were clinical. Prenatal diagnoses accounted for 1.2%. Familial recurrence and consanguinity rates were 21.6% and 6.4%, respectively. Mainstay treatments included drug therapy (55.0%) and rehabilitation (15.6%). The Public Health System funded most diagnoses (84.2%) and treatments (86.7%). Hospitalizations were reported in 44.5% of cases, and the mortality rate was 1.5%, primarily due to motor neuron disease and CF. Conclusion This study marks a pioneering national-level data collection effort for rare diseases in Brazil, offering novel insights to advance the understanding, management, and resource allocation for RDs. It unveils an average diagnostic odyssey of 5.4 years and a higher prevalence of PKU and CF, possibly associated with the specialized services network, which included newborn screening services.

Abstract Rapid sub-nanometer neuronal deformations have been shown to occur as a consequence of action potentials in vitro, allowing for optical registration of discrete axonal and synaptic depolarizations. Such optically-measured deformations are a novel signature for recording neural activity. We demonstrate this signature can be extended to in vivo measurements through recording of rapid neuronal deformations on the population level with holographic, optical phase-based recordings. Our system demonstrates, for the first time, non-invasive recordings of in vivo tissue deformation associated with population level neuronal activity, including through-skull. We confirmed this technique across a range of neural activation models, including direct epidural focal electrical stimulation, anesthetic-induced cortical deactivation, activation of primary somatosensory cortex via whisker barrel stimulation, and pharmacologically-induced seizures. Collectively, we show holographic imaging provides a pathway for high-resolution, label-free, non-invasive recording of transcranial in vivo neural activity at depth, making it highly advantageous for studying neural function and signaling.

Abstract A single-center, prospective, observational pilot study was performed to evaluate wound healing endpoint and recurrence by measuring transepidermal water loss (TEWL) post-closure at the site of wound repair. Patients with clinically-defined chronic wounds (such as pressure ulcers, diabetic ulcers, and trauma wounds) who visited the Plastic Surgery outpatient department or were in-patients at the All India Institute of Medical Sciences, Rishikesh, India, and were referred for chronic wound management, were enrolled. Non-invasive point-of-care TEWL measurements were obtained, from closed wound-site and contralateral healthy skin site, starting from confirmation of closure (post-closure, V0) continuing every 2 weeks for a maximum of five visits or until the wound recurred. Statistical analyses of the data involved logistic regression and likelihood ratio chi-square tests to assess differences in TEWL at visit 0 (V0) between the closed wound site and reference skin, with the TEWL score as the sole predictor of recurrence. Of the 72 subjects that completed the study, 44 (61%) showed no recurrence and 28 (39%) had wounds that recurred over a period of 12 weeks. A significant association was found between the V0 (post-closure) TEWL score and the odds of wound recurrence, both in univariate analysis (OR [95%CI] = 1.26[1.14,1.42] (p

Abstract Purpose Diagnosing and treating obstructive sleep apnea (OSA) requires fundamental understanding of sleep medicine, including training and clinical experience. So far, dental sleep medicine (DSM) has not yet become a mandatory part of dental education in Germany. This questionnaire-based survey for both lecturers and students aimed to evaluate DSM education among undergraduate students. Methods A structured questionnaire was sent to the managing directors and student councils of all 30 German university dental schools. The questionnaire contained 13 questions on teaching quantity and content, lecturers’ knowledge, and future interest in DSM. For each university dental school, only one questionnaire should be completed by the student council and the managing director. A scoring system assessed lecturers’ knowledge based on clinical experience and qualifications. Descriptive data and correlation coefficients were calculated (P

Abstract Background Having previously shown headache disorders to be prevalent in Mongolia, here we elaborate on headache as a public-health concern in this country, reporting symptom burden and headache-attributed impaired participation at individual and societal levels, and conducting a health-care needs assessment. Methods The study followed the standardized methodology developed by the Global Campaign against Headache, generating a representative general-population sample through multi-level randomized cluster sampling. Participants aged 18–65 years were interviewed at unannounced household visits by interviewers administering the HARDSHIP questionnaire. Symptom burden was established through questions on frequency, duration and intensity of headache, with proportion of time in ictal state calculated from frequency and duration. Individual impaired participation was established through the HALT questionnaire, enquiring into lost time from paid and household work and from leisure activities. Symptom burden and impaired participation yesterday were also assessed in those reporting headache yesterday. Population-level estimates were derived by factoring in prevalence. Results The total sample included 2,043 participants. Those reporting any headache in the last year (n = 1,351) spent, on average, 9.7% of all their time with headache, losing 1.3 workdays and 2.4 household days/3 months. These losses were considerably higher among those with probable medication-overuse headache (37.5%, 3.5 workdays, 6.7 household days) or other headache on ≥ 15 days/month (H15+) (21.9%, 2.4 workdays, 5.1 household days). At population-level (including those with and without headache), 6.2–7.4% of all time was spent with headache, 3.1% with H15+; 0.8 workdays and 1.4 household days/person/3 months were lost to headache, 0.3 workdays and 0.6 household days to migraine (the biggest contributor of all headache types). Our needs assessment estimated that one third (33.2%) of the adult population of Mongolia have headache (mostly migraine or H15+) likely to benefit from health care. Conclusion This first population-based study on headache burden in Mongolia shows high levels of individual and societal burden, with H15 + the cause of greater burden at population level than migraine and TTH combined. Migraine, however, has the biggest impact on the nation’s productivity. From a purely economic perspective, Mongolia, with limited health resources, would probably be best served by focusing on mitigating migraine-attributed burden.

Abstract Background Acute myeloid leukemia (AML) is characterized by the abnormal proliferation of myeloid precursor cells and presents significant challenges in treatment due to its heterogeneity. Recently, the NLRP3 inflammasome has emerged as a potential contributor to AML pathogenesis, although its precise mechanisms remain poorly understood. Methods Public genome datasets were utilized to evaluate the expression of NLRP3 inflammasome-related genes (IL-1β, IL-18, ASC, and NLRP3) in AML patients compared to healthy individuals. CRISPR/Cas9 technology was employed to generate NLRP3-deficient MOLM-13 AML cells, followed by comprehensive characterization using real-time PCR, western blotting, FACS analysis, and transmission electron and immunofluorescence microscopy. Proteomic analyses were conducted to identify NLRP3-dependent alterations in protein levels, with a focus on the eIF2 kinase PERK-mediated signaling pathways. Additionally, in vivo studies were performed using a leukemic mouse model to elucidate the pathogenic role of NLRP3 in AML. Results Elevated expression of NLRP3 was significantly associated with diminished overall survival in AML patients. Genetic deletion, pharmacological inhibition and silencing by RNA interference of NLRP3 led to decreased AML cell survival through the induction of apoptosis. Proteomic analyses uncovered NLRP3-dependent alterations in protein translation, characterized by enhanced eIF2α phosphorylation in NLRP3-deficient AML cells. Moreover, inhibition of PERK-mediated eIF2α phosphorylation reduced apoptosis by downregulating pro-apoptotic Bcl-2 family members. In vivo studies demonstrated reduced leukemic burden in mice engrafted with NLRP3 knockout AML cells, as evidenced by alleviated leukemic symptoms. Conclusion Our findings elucidate the involvement of the NLRP3/PERK/eIF2 axis as a novel driver of AML cell survival. Targeting NLRP3-induced signaling pathways, particularly through the PERK/eIF2 axis, presents a promising therapeutic strategy for AML intervention. These insights into the role of the NLRP3 inflammasome offer potential avenues for improving the prognosis and treatment outcomes of AML patients.

Western equine encephalitis virus (WEEV) is a mosquitoborne virus that reemerged in December 2023 in Argentina and Uruguay, causing a major outbreak. We investigated the outbreak using epidemiologic, entomological, and genomic analyses, focusing on WEEV circulation near the Argentina‒Uruguay border in Rio Grande do Sul state, Brazil. During November 2023‒April 2024, the outbreak in Argentina and Uruguay resulted in 217 human cases, 12 of which were fatal, and 2,548 equine cases. We determined cases on the basis of laboratory and clinical epidemiologic criteria. We characterized 3 fatal equine cases caused by a novel WEEV lineage identified through a nearly complete coding sequence analysis, which we propose as lineage C. Our findings highlight the importance of continued surveillance and equine vaccination to control future WEEV outbreaks in South America.

Abstract Background A global schools-based programme within the Global Campaign against Headache is estimating the burden of headache in children (6–11 years) and adolescents (12–17 years), cluster-sampling the world by conducting national studies in all world regions. Its purpose is to complement population-based studies in adults, adding to knowledge of the burden of headache and informing educational and health policies. This study in Benin was the third in the programme from sub-Saharan Africa (SSA). Methods We followed the generic protocol for the global study. In a cross-sectional survey, the child and adolescent versions of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaire were administered to pupils within their classes in 16 schools selected from across the country to be representative of its diversities. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of undifferentiated headache (UdH). Results Very large proportions of pupils were absent on the survey days. The sampled population defined by class registers totalled 11,802 pupils, of whom only 2,488 were present. A further 193 pupils (or their parents) declined the survey. The surveyed sampled (N = 2,295; males 1,156 [50.4%], females 1,139 [49.6%]) included 1,081 children (47.1%) and 1,214 adolescents (52.9%), with a non-participating proportion (193/2,488) of 7.8%. Headache ever was reported by 97.3% of the sample. Age- and gender-adjusted 1-year prevalences, according to responses given, were 53.4% for migraine (almost three quarters of this being probable migraine), 21.3% for tension-type headache, 8.2% for UdH, 1.0% for probable medication-overuse headache (pMOH) and 2.6% for other headache on ≥ 15 days/month (H15+). Both pMOH and other H15 + were substantially more prevalent among adolescents. Conclusion The finding for migraine is anomalous, but, within this series of studies, the same was found in Zambia and similar in Ethiopia, both in SSA. While many cases identified as probable migraine, especially among children, might better have been diagnosed as UdH, the true prevalence of migraine almost certainly exceeds 21%. Regardless of diagnosis, headache is very common among children and adolescents in Benin. The study sounds an alarm with regard to pMOH as a developing problem pre-adulthood.

Abstract Background We have previously shown headache to be highly prevalent in Cameroon. Here we present the attributed burden. We also perform a headache-care needs assessment. Methods This was a cross-sectional survey among adults (18–65 years) in the general population. Multistage cluster-sampling in four regions (Centre, Littoral, West and Adamawa), home to almost half the country’s population, generated a representative sample. We used the standardised methodology of the Global Campaign against Headache, including the HARDSHIP questionnaire, with diagnostic questions based on ICHD-3 and enquiries into symptom burden, impaired participation (lost productivity and disengagement from social activity), quality of life (QoL) using WHOQoL-8, and willingness to pay (WTP) for effective care. We defined headache care “need” in terms of likelihood of benefit, counting all those with probable medication-overuse headache (pMOH) or other headache on ≥ 15 days/month (H15 +), with migraine on ≥ 3 days/month, or with migraine or tension-type headache (TTH) and meeting either of two criteria: a) proportion of time in ictal state (pTIS) > 3.3% and intensity ≥ 2 (moderate-to-severe); or b) ≥ 3 lost days from paid and/or household work in the preceding 3 months. Results Among 3,100 participants, mean frequency of any headache was 6.7 days/month, mean duration 13.0 h and mean intensity 2.3 (moderate). Mean pTIS was 9.8%, which (with prevalence factored in) diluted to 6.1–7.4% of all time in the population. Most time was spent with H15 + (5.3% of all time), followed by TTH (1.0%) and migraine (0.8%). For all headache, mean lost days/3 months were 3.4 from paid work, 3.0 from household work and 0.6 from social/leisure activities, diluting to 2.5, 2.2 and 0.6 days/3 months in the population. QoL (no headache: 27.9/40) was adversely impacted by pMOH (25.0) and other H15 + (26.0) but not by migraine (28.0) or TTH (28.0). WTP (maximally XAF 4,462.40 [USD 7.65] per month) was not significantly different between headache types. An estimated 37.0% of adult Cameroonians need headache care. Conclusion Headache disorders in Cameroon are not only prevalent but also associated with high attributed burden, with heavily impaired participation. Headache-care needs are very high, but so are the economic costs of not providing care.

Abstract Background Tumor-Adipose-Feature (TAF) as well as SARIFA (Stroma AReactive Invasion Front Areas) are two histologic features/biomarkers linking tumor-associated adipocytes to poor outcomes in colorectal cancer (CRC) patients. Whereas TAF was identified by deep learning (DL) algorithms, SARIFA was established as a human-observed histopathologic biomarker. Methods To study the overlap between TAF and SARIFA, we performed a systematic pathological review of TAF based on all published image tiles. Additionally, we analyzed the presence/absence of TAF in SARIFA-negative CRC cases to elucidate the biologic and prognostic role of a direct tumor-adipocyte contact. TCGA-CRC gene expression data is investigated to assess the association of FABP4 (fatty-acid binding protein 4) and CD36 (fatty-acid translocase) with both TAF and CRC prognosis. Results By investigating the TAF/SARIFA overlap, we show that many TAF patches correspond to the recently described SARIFA-phenomenon. Even though there is a pronounced morphological and biological overlap, there are differences in the concepts. The presence of TAF in SARIFA-negative CRCs is not associated with poor outcomes in this cohort, potentially highlighting the importance of a direct tumor-adipocyte interaction. Upregulation of FABP4 and CD36 gene expression seem both linked to a poor prognosis in CRC. Conclusions By proving the substantial overlap between human-observed SARIFA and DL-based TAF as morphologic biomarkers, we demonstrate that linking DL-based image features to independently developed histopathologic biomarkers is a promising tool in the identification of clinically and biologically meaningful biomarkers. Adipocyte-tumor-cell interactions seem to be crucial in CRC, which should be considered as biomarkers for further investigations.

Abstract The risk of venous thromboembolism (VTE) increases with age. However, the risk of VTE in the setting of long-term care hospitals is understudied. Our objective was to provide data on the prevalence and incidence of VTE in older adults admitted to long-term care hospitals. In this retrospective cohort study, we collected data about chronically ill and multimorbid patients aged 65 years and older from two long-term care hospitals. The primary endpoint of this study was the lifetime prevalence of VTE, and the secondary endpoint was VTE incidence during residency in long-term care hospitals. We analysed data from 1148 patients with a mean age of 84.1 ± 7.9 years, of whom 74.2% were women. The lifetime prevalence of VTE at baseline was 9.6% (95% CI 7.9–11.4). Cumulative incidence of VTE at 1, 2, and 3 years from baseline was estimated at 3.5% (95% CI 2.5–4.7), 4.2% (95% CI 3.1–5.5), and 5.4% (95% CI 4.1–7.0), respectively. Overall, the incidence rate of VTE in our study was 2.82 (95% CI 2.18–3.66) per 100 person-years. The study indicated a considerably high lifetime prevalence and incidence of VTE during residence in long-term care hospital settings, requiring further evaluation in larger prospective studies.

Abstract Microbubbles (MBs) combined with focused ultrasound (FUS) has emerged as a promising noninvasive technique to permeabilize the blood–brain barrier (BBB) for drug delivery into the brain. However, the safety and biological consequences of BBB opening (BBBO) remain incompletely understood. This study aims to investigate the effects of two parameters mediating BBBO: microbubble volume dose (MVD) and mechanical index (MI). High-resolution MRI-guided FUS was employed in mouse brains to assess BBBO by manipulating these two parameters. Afterward, the sterile inflammatory response (SIR) was studied 6 h post-FUS treatment. Results demonstrated that both MVD and MI significantly influenced the extent of BBBO, with higher MVD and MI leading to increased permeability. Moreover, RNA sequencing revealed upregulation of major inflammatory pathways and immune cell infiltration after BBBO, indicating the presence and extent of SIR. Gene set enrichment analysis identified 12 gene sets associated with inflammatory responses that were significantly upregulated at higher MVD or MI. A therapeutic window was established between therapeutically relevant BBBO and the onset of SIR, providing operating regimes to avoid damage from stimulation of the NFκB pathway via TNFɑ signaling to apoptosis. These results contribute to the optimization and standardization of BBB opening parameters for safe and effective drug delivery to the brain and further elucidate the underlying molecular mechanisms driving sterile inflammation.

Abstract Carbon dioxide (CO $$_2$$ 2 ) trapping in capillary networks of reservoir rocks is a pathway to long-term geological storage. At pore scale, CO $$_2$$ 2 drainage displacement depends on injection pressure, temperature, and the rock’s interaction with the surrounding fluids. Modeling this interaction requires adequate representations of both capillary volume and surface. For the lack of scalable representations, however, the prediction of a rock’s CO $$_2$$ 2 storage potential has been challenging. Here, we report how to represent a rock’s pore space by statistically sampled capillary networks (ssCN) that preserve morphological rock characteristics. We have used the ssCN method to simulate CO $$_2$$ 2 drainage within a representative sandstone sample at reservoir pressures and temperatures, exploring intermediate- and CO $$_2$$ 2 -wet conditions. This wetting regime is often neglected, despite evidence of plausibility. By raising pressure and temperature we observe increasing CO $$_2$$ 2 penetration within the capillary network. For contact angles approaching 90 $$^\circ$$ ∘ , the CO $$_2$$ 2 saturation exhibits a pronounced maximum reaching 80 $$\%$$ % of the accessible pore volume. This is about twice as high as the saturation values reported previously. For enabling validation of our results and a broader application of our methodology, we have made available the rock tomography data, the digital rock computational workflows, and the ssCN models used in this study.

Dorvilleidae Chamberlin, 1919 is a family of Annelida containing some of the smallest ‘polychaetes’ species, being poorly studied worldwide, and with little knowledge regarding its diversity and occurrence. Samples obtained in oceanographic campaigns performed in the Southwest Atlantic Ocean (Brazilian coast) revealed a high number of specimens of dorvilleids, adding to our knowledge of the family’s biodiversity. A detailed morphological analysis of these organisms has revealed a new genus, Ceciamaralia gen. nov., with two new species. The new genus differs from other Dorvilleidae genera in (i) the robust and enlarged pharynx which are frequently everted, (ii) unique composition of maxillae, with an elongated pair of serrated basal plates and one pair of anterior free maxillary plates with a long and thin anterior spine and (iii) ventral cirri present only in few first chaetigers. Ceciamaralia lanai gen. et sp. nov. is characterized by the presence of a broad and large dorsal cirrus on a few anterior parapodia and by furcate chaeta in supra-acicular fascicles. While Ceciamaralia nonatoi gen. et sp. nov. presents one geniculate chaeta instead of one furcate, the absence of dorsal cirri and, in some specimens, the absence of palps. A cladistic analysis supported the monophyly of Ceciamaralia gen. nov. by four synapomorphies related to the unique morphology of its maxillae, pharynx and appendages. This study is part of several recent taxonomic studies aiming to elucidate and increase the knowledge of Dorvilleidae, since it is part of a Ph.D project focused on the family.

Abstract High sugar consumption is associated with cardiovascular diseases and diabetes. Current sugar substitutes may cause taste sensations and gastrointestinal symptoms. ENSO 16 is a combination of 16 different sugar substitutes and plant fibers and has been designed as a sugar alternative. The impact on plasma glucose metabolism as well as on gastrointestinal tolerance has not been investigated yet. 17 healthy participants were enrolled in this randomized, double-blind trial. Participants received a single oral dose of 30 g glucose or 30 g ENSO 16 and crossed over to the alternate treatment after a 7 day wash out period. The study endpoint was the effect on plasma glucose, insulin, C-peptide concentrations and gastrointestinal disorders. A questionnaire regarding gastrointestinal symptoms was used for individual subjective scoring. The mean baseline adjusted plasma glucose AUC0–180 min was significantly greater after glucose administration compared to ENSO 16 (n = 15, p = 0.0128, paired t-test). Maximum plasma glucose elevation over baseline was 117 mg*dl−1 and 20 mg*dl−1 after oral glucose or ENSO 16, respectively. Insulin and C-peptide AUC0−180 min were significantly greater after glucose compared to ENSO 16 intake (p

Abstract Background India is a large and populous country where reliable data on headache disorders are relatively scarce. This study in northern India (Delhi and National Capital Territory Region [NCR], including surrounding districts in the States of Haryana, Uttar Pradesh and Rajasthan) continues the series of population-based studies within the Global Campaign against Headache and follows an earlier study, using the same protocol and questionnaire, in the southern State of Karnataka. Methods This cross-sectional study used the Global Campaign’s established methodology. Biologically unrelated Indian nationals aged 18–65 years were included through multistage random sampling in both urban and rural areas of NCR. Interviews at unannounced household visits followed the structured Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire in its original English version or in the validated Hindi version. Demographic enquiry was followed by a neutral headache screening question and diagnostic questions based on the International Classification of Headache Disorders edition 3 (ICHD-3), which focused on each respondent’s most bothersome headache. Questions about headache yesterday (HY) enabled estimation of 1-day prevalence. A diagnostic algorithm first identified participants reporting headache on ≥ 15 days/month (H15+), diagnosing probable medication-overuse headache (pMOH) in those also reporting acute medication use on ≥ 15 days/month, and “other H15+” in those not. To all others, the algorithm applied ICHD-3 criteria in the order definite migraine, definite tension-type headache (TTH), probable migraine, probable TTH. Definite and probable diagnoses were combined. Results Adjusted for age, gender and habitation, 1-year prevalences were 26.3% for migraine, 34.1% for TTH, 3.0% for pMOH and 4.5% for other H15+. Female preponderance was seen in all headache types except TTH: migraine 35.7% vs. 15.1% (aOR = 3.3; p

Abstract Background Our recent studies have shown headache disorders to be very common in the central and western sub-Saharan countries of Benin and Cameroon. Here we report headache in nearby Mali, a strife-torn country that differs topographically, culturally, politically and economically. The purposes were to estimate headache-attributed burden and need for headache care. Methods We used cluster-random sampling in seven of Mali’s eleven regions to obtain a nationally representative sample. During unannounced household visits by trained interviewers, one randomly selected adult member (18–65 years) from each household was interviewed using the structured HARDSHIP questionnaire, with enquiries into headache in the last year and, additionally, headache yesterday (HY). Headache on ≥ 15 days/month (H15+) was diagnosed as probable medication-overuse headache (pMOH) when associated with acute medication use on ≥ 15 days/month, and as “other H15+” when not. Episodic headache (on

Abstract Background We recently found headache disorders to be highly prevalent among children (aged 6–11 years) and adolescents (aged 12–17) in Iran (gender- and age-adjusted 1-year prevalences: migraine 25.2%, tension-type headache 12.7%, undifferentiated headache [UdH] 22.1%, probable medication-overuse headache [pMOH] 1.1%, other headache on ≥ 15 days/month [H15+] 3.0%). Here we report on the headache-attributed burden, taking evidence from the same study. Methods In a cross-sectional survey, following the generic protocol for the global schools-based study led by the Global Campaign against Headache, we administered the child and adolescent versions of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaire in 121 schools, purposively selected to reflect the country’s diversities. Pupils self-completed these in class, under supervision. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of UdH (defined as mild headache with usual duration

Abstract Rodent models and human clinical studies have shown gut microbiota-derived short-chain fatty acids (SCFAs) play roles in obesity and insulin resistance. These roles have been minimally explored in cats, where in the USA an estimated 60% of cats are overweight or obese. Overweight/obese research cats (n = 7) were transitioned from a maintenance diet to a reduced calorie diet fed ad libitum for 7 days, then calories were restricted to achieve 1–2% weight loss per week for an additional 77 days. Cats then received their original maintenance diet again for 14 days. Significant intentional weight loss was noted after calorie restriction (adjusted p

Abstract Background There are no robust population-based Australian data on prevalence and attributed burden of migraine and medication-overuse headache (MOH) data. In this pilot cross-sectional study, we aimed to capture the participation rate, preferred response method, and acceptability of self-report questionnaires to inform the conduct of a future nationwide migraine/MOH epidemiological study. Methods We developed a self-report questionnaire, available in hard-copy and online, including modules from the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, the Eq. 5D (quality of life), and enquiry into treatment gaps. Study invitations were mailed to 20,000 randomly selected households across Australia’s two most populous states. The household member who most recently had a birthday and was aged ≥ 18 years was invited to participate, and could do so by returning a hard-copy questionnaire via reply-paid mail, or by entering responses directly into an online platform. Results The participation rate was 5.0% (N = 1,000). Participants’ median age was 60 years (IQR 44–71 years), and 64.7% (n = 647) were female. Significantly more responses were received from areas with relatively older populations and middle-level socioeconomic status. Hard copy was the more commonly chosen response method (n = 736). Females and younger respondents were significantly more likely to respond online than via hard-copy. Conclusions This pilot study indicates that alternative methodology is needed to achieve satisfactory engagement in a future nationwide migraine/MOH epidemiological study, for example through inclusion of migraine screening questions in well-resourced, interview-based national health surveys that are conducted regularly by government agencies. Meanwhile, additional future research directions include defining and addressing treatment gaps to improve migraine awareness, and minimise under-diagnosis and under-treatment.

Abstract Background The fundamental prerequisite for prognostically favorable postoperative results of peripheral nerve repair is stable neurorrhaphy without interruption and gap formation. Methods This study evaluates 60 neurorrhaphies on femoral chicken nerves in terms of the procedure and the biomechanical properties. Sutured neurorrhaphies (n = 15) served as control and three sutureless adhesive-based nerve repair techniques: Fibrin glue (n = 15), Histoacryl glue (n = 15), and the novel polyurethane adhesive VIVO (n = 15). Tensile and elongation tests of neurorrhaphies were performed on a tensile testing machine at a displacement rate of 20 mm/min until failure. The maximum tensile force and elongation were recorded. Results All adhesive-based neurorrhaphies were significant faster in preparation compared to sutured anastomoses (p

Abstract Background We have previously shown headache to be highly prevalent among adults in Saudi Arabia. Here we estimate associated symptom burden and impaired participation (impaired use of time, lost productivity and disengagement from social activity), and use these estimates to assess headache-related health-care needs in Saudi Arabia. Methods A randomised cross-sectional survey included 2,316 adults (18–65 years) from all 13 regions of the country. It used the standardised methodology of the Global Campaign against Headache with a culturally mandated modification: engagement by cellphone using random digit-dialling rather than door-to-door visits. Enquiry used the HARDSHIP questionnaire, with diagnostic questions based on ICHD-3 beta, questions on symptom burden, enquiries into impaired participation using the HALT index and questions about activity yesterday in those reporting headache yesterday (HY). Health-care “need” was defined in terms of likelihood of benefit. We counted all those with headache on ≥ 15 days/month, with migraine on ≥ 3 days/month, or with migraine or TTH and meeting either of two criteria: a) proportion of time in ictal state (pTIS) > 3.3% and intensity ≥ 2 (moderate-severe); b) ≥ 3 lost days from paid work and/or household chores during 3 months. Results For all headache, mean frequency was 4.3 days/month, mean duration 8.4 h, mean intensity 2.3 (moderate). Mean pTIS was 3.6%. Mean lost days from work were 3.9, from household chores 6.6, from social/leisure activities 2.0. Of participants reporting HY, 37.3% could do less than half their expected activity, 19.8% could do nothing. At population-level (i.e., for every adult), 2.5 workdays (potentially translating into lost GDP), 3.6 household days and 1.3 social/leisure days were lost to headache. According to HY data, mean total impaired participation (not distinguishing between work, household and social/leisure) was 6.8%. A total of 830 individuals (35.8%) fulfilled one or more of our needs assessment criteria. Conclusion A very high symptom burden is associated with a commensurately high burden of impaired participation. The economic cost appears to be enormous. Over a third of the adult population are revealed to require headache-related health care on the basis of being likely to benefit, demanding highly efficient organization of care.

Abstract To evaluate immune responses to COVID-19 vaccines in adults aged 50 years and older, spike protein (S)-specific antibody concentration, avidity, and function (via angiotensin-converting enzyme 2 (ACE2) inhibition surrogate neutralization and antibody dependent cellular phagocytosis (ADCP)), as well as S-specific T cells were quantified via activation induced marker (AIM) assay in response to two-dose series. Eighty-four adults were vaccinated with either: mRNA/mRNA (mRNA-1273 and/or BNT162b2); ChAdOx1-S/mRNA; or ChAdOx1-S/ChAdOx1-S. Anti-S IgG concentrations, ADCP scores and ACE2 inhibiting antibody concentrations were highest at one-month post-second dose and declined by four-months post-second dose for all groups. mRNA/mRNA and ChAdOx1-S/mRNA schedules had significantly higher antibody responses than ChAdOx1-S/ChAdOx1-S. CD8+ T-cell responses one-month post-second dose were associated with increased ACE2 surrogate neutralization. Antibody avidity (total relative avidity index) did not change between one-month and four-months post-second dose and did not significantly differ between groups by four-months post-second dose. In determining COVID-19 correlates of protection, a measure that considers both antibody concentration and avidity should be considered.

Abstract Background We previously reported high prevalences of headache disorders among children (6–11 years) and adolescents (12–17 years) in Ethiopia. Here we provide data on headache-attributed burden collected contemporaneously from the same study participants. Part of the global schools-based programme within the Global Campaign against Headache, the study is the first to present such data from sub-Saharan Africa. Methods A cross-sectional survey following the generic protocol for the global study was conducted in six schools (urban and rural), in Addis Ababa city and three regions of Ethiopia. The child or adolescent versions of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaires were self-completed under supervision by pupils in class. Headache diagnostic questions were based on ICHD-3 beta but for the inclusion of undifferentiated headache (UdH). Results Of 2,349 eligible participants, 2,344 completed the questionnaires (1,011 children [43.1%], 1,333 adolescents [56.9%]; 1,157 males [49.4%], 1,187 females [50.6%]; participating proportion 99.8%). Gender- and age-adjusted 1-year prevalence of headache, reported previously, was 72.8% (migraine: 38.6%; tension-type headache [TTH]: 19.9%; UdH: 12.3%; headache on ≥ 15 days/month (H15+): 1.2%). Mean headache frequency was 2.6 days/4 weeks but, with mean duration of 2.7 h, mean proportion of time with headache was only 1.0% (migraine: 1.4%; TTH: 0.7%; H15+: 9.1%). Mean intensity was 1.8 on a scale of 1–3. Symptomatic medication was consumed on about one third of headache days across headache types. Lost school time reportedly averaged 0.7 days over the preceding 4 weeks, representing 3.5% of school time, but was 2.4 days/4 weeks (12.0%) in the important small minority with H15+. However, actual absences with headache the day before indicated averages overall of 9.7% of school time lost, and 13.3% among those with migraine. Emotional impact and quality-of-life scores reflected other measures of burden, with clear adverse impact gradients (H15 + > migraine > TTH > UdH). Conclusions The high prevalence of headache among children and adolescents in Ethiopia, who represent half its population, is associated with substantial burden. Lost school time is probably the most important consequence. Estimates suggest a quite deleterious effect, likely to be reflected in both individual prospects and the prosperity of society.

Abstract Background The series of population-based studies conducted by the Global Campaign against Headache has, so far, included Pakistan and Saudi Arabia from the Eastern Mediterranean Region. The Maghreb countries of North Africa, also part of this Region, are geographically apart and culturally very different from these countries. Here we report a study in Morocco. Methods We applied the standardised methodology of Global Campaign studies, with cluster-randomized sampling in regions of Morocco selected to be representative of its diversities. In three of these regions, in accordance with this methodology, we made unannounced visits to randomly selected households and, from each, interviewed one randomly selected adult member (aged 18–65 years) using the HARDSHIP structured questionnaire translated into Moroccan Arabic and French. In a fourth region (Fès), because permission for such sampling was not given by the administrative authority, people were randomly stopped in streets and markets and, when willing, interviewed using the same questionnaire. This was a major protocol violation. Results We included 3,474 participants, 1,074 (41.7%) from Agadir, 1,079 (41.9%) from Marrakech, 422 (16.4%) from Tétouan and 899 from Fès. In a second protocol violation, interviewers failed to record the non-participating proportion. In the main analysis, excluding Fès, observed 1-year prevalence of any headache was 80.1% among females, 68.2% among males. Observed 1-day prevalence (headache yesterday) was 17.8%. After adjustment for age and gender, migraine prevalence was 30.8% (higher among females [aOR = 1.6]) and TTH prevalence 32.1% (lower among females [aOR = 0.8]). Headache on ≥ 15 days/month (H15+) was very common (10.5%), and in more than half of cases (5.9%) associated with acute medication overuse (on ≥ 15 days/month) and accordingly diagnosed as probable medication-overuse headache (pMOH). Both pMOH (aOR = 2.6) and other H15+ (aOR = 1.9) were more common among females. In the Fès sample, adjusted prevalences were similar, numerically but not significantly higher except for other H15+. Conclusions While the 1-year prevalence of headache among adults in Morocco is similar to that of many other countries, migraine on the evidence here is at the upper end of the global range, but not outside it. H15 + and pMOH are very prevalent, contributing to the high one-day prevalence of headache.

Abstract Background The Global Campaign against Headache is conducting a series of population-based studies to fill the large geographical gaps in knowledge of headache prevalence and attributable burden. One major region not until now included is South America. Here we present a study from Peru, a country of 32.4 million inhabitants located at the west coast of South America, notable for its high Andes mountains. Methods The study was conducted in accordance with the standardized methodology used by the Global Campaign. It was a cross-sectional survey using cluster randomised sampling in five regions to derive a nationally representative sample, visiting households unannounced, and interviewing one randomly selected adult member (aged 18–65 years) of each using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire translated into South American Spanish. The neutral screening question (“Have you had headache in the last year?”) was followed by diagnostic questions based on ICHD-3 and demographic enquiry. Results The study included 2,149 participants from 2,385 eligible households (participating proportion 90.1%): 1,065 males and 1,084 females, mean age 42.0 ± 13.7 years. The observed 1-year prevalence of all headache was 64.6% [95% CI: 62.5–66.6], with age-, gender- and habitation-adjusted prevalences of 22.8% [21.0-24.6] for migraine (definite + probable), 38.9% [36.8–41.0] for tension-type headache (TTH: also definite + probable), 1.2% [0.8–1.8] for probable medication-overuse headache (pMOH) and 2.7% [2.1–3.5] for other headache on ≥ 15 days/month (H15+). One-day prevalence of headache (reported headache yesterday) was 12.1%. Migraine was almost twice as prevalent among females (28.2%) as males (16.4%; aOR = 2.1; p 3,500 versus

Abstract Background The Global Burden of Disease (GBD) study is increasingly well informed with regard to headache disorders, but sub-Saharan Africa (SSA) remains one of the large regions of the world with limited data directly derived from population-based studies. The Global Campaign against Headache has conducted three studies in this region: Ethiopia in the east, Zambia in the south and Cameroon in Central SSA. Here we report a similar study in Benin, the first from West SSA. Methods We used the same methods and questionnaire, applying cluster-randomized sampling in three regions of the country, randomly selecting households in each region, visiting these unannounced and randomly selecting one adult member (aged 18–65 years) of each household. The HARDSHIP structured questionnaire, translated into Central African French, was administered face-to-face by trained interviewers. Demographic enquiry was followed by diagnostic questions based on ICHD-3 criteria. Results From 2,550 households with eligible members, we recruited 2,400 participants (participating proportion 94.1%). Headache ever was reported by almost all (95.2%), this being the lifetime prevalence. Headache in the last year was reported by 74.9%. Age-, gender- and habitation-adjusted estimates of 1-year prevalence were 72.9% for all headache, 21.2% for migraine (including definite and probable), 43.1% for TTH (also including definite and probable), 4.5% for probable medication-overuse (pMOH) and 3.1% for other headache on ≥ 15 days/month. One-day (point) prevalence of headache was 14.8% according to reported headache on the day preceding interview. Conclusions Overall, these findings are evidence that headache disorders are very common in Benin, a low-income country. The prevalence of pMOH, well above the estimated global mean of 1–2%, is evidence that poverty is not a bar to medication overuse. The findings are very much the same as those in a similar study in its near neighbour, Cameroon. With regard to migraine, they are reasonably in accord with two of three earlier studies in selected Beninese populations, which did not take account of probable migraine. This study adds to the hitherto limited knowledge of headache in SSA.

During October 2021–June 2023, a total of 392 cases of acute hepatitis of unknown etiology in children in the United States were reported to Centers for Disease Control and Prevention as part of national surveillance. We describe demographic and clinical characteristics, including potential involvement of adenovirus in development of acute hepatitis, of 8 fatally ill children who met reporting criteria. The children had diverse courses of illness. Two children were immunocompromised when initially brought for care. Four children tested positive for adenovirus in multiple specimen types, including 2 for whom typing was completed. One adenovirus-positive child had no known underlying conditions, supporting a potential relationship between adenovirus and acute hepatitis in previously healthy children. Our findings emphasize the importance of continued investigation to determine the mechanism of liver injury and appropriate treatment. Testing for adenovirus in similar cases could elucidate the role of the virus.

BackgroundDecades of research have transformed hemophilia from severely limiting children's lives to a manageable disorder compatible with a full, active life, for many in high-income countries. The direction of future research will determine whether exciting developments truly advance health equity for all people with hemophilia (PWH). National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive inclusive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them.Research design and methodsWorking group (WG) 1 of the NHF State of the Science Research Summit distilled the community-identified priorities for hemophilia A and B into concrete research questions and scored their feasibility, impact, and risk.ResultsWG1 defined 63 top priority research questions concerning arthropathy/pain/bone health, inhibitors, diagnostics, gene therapy, the pediatric to adult transition of care, disparities faced by the community, and cardiovascular disease. This research has the potential to empower PWH to thrive despite lifelong comorbidities and achieve new standards of wellbeing, including psychosocial.ConclusionsCollaborative research and care delivery will be key to capitalizing on current and horizon treatments and harnessing technical advances to improve diagnostics and testing, to advance health equity for all PWH.

IntroductionMolecular chaperones and co-chaperones are highly conserved cellular components that perform a variety of duties related to the proper three-dimensional folding of the proteome. The web of factors that carries out this essential task is called the proteostasis network (PN). Ribonucleoproteins (RNPs) represent an underexplored area in terms of the connections they make with the PN. The Survival Motor Neuron (SMN) complex is an assembly chaperone and serves as a paradigm for studying how specific RNAs are identified and paired with their client substrate proteins to form RNPs. SMN is the eponymous component of a large complex, required for the biogenesis of uridine-rich small nuclear ribonucleoproteins (U-snRNPs), that localizes to distinct membraneless organelles in both the nucleus and cytoplasm of animal cells. SMN protein forms the oligomeric core of this complex, and missense mutations in the human SMN1 gene are known to cause Spinal Muscular Atrophy (SMA). The basic framework for understanding how snRNAs are assembled into U-snRNPs is known. However, the pathways and mechanisms used by cells to regulate their biogenesis are poorly understood.MethodsGiven the importance of these processes to normal development as well as neurodegenerative disease, we set out to identify and characterize novel SMN binding partners. We carried out affinity purification mass spectrometry (AP-MS) of Drosophila SMN complexes using fly lines exclusively expressing either wildtype or SMA-causing missense alleles.ResultsBioinformatic analyses of the pulldown data, along with comparisons to proximity labeling studies carried out in human cells, revealed conserved connections to at least two other major chaperone systems including heat shock folding chaperones (HSPs) and histone/nucleosome assembly chaperones. Notably, we found that heat shock cognate protein Hsc70-4 and other HspA family members preferentially associated with SMA-causing alleles of SMN.DiscussionHsc70-4 is particularly interesting because its mRNA is aberrantly sequestered by a mutant form of TDP-43 in mouse and Drosophila ALS (Amyotrophic Lateral Sclerosis) disease models. Most important, a missense allele of Hsc70-4 (HspA8 in mammals) was recently identified as a bypass suppressor of the SMA phenotype in mice. Collectively, these findings suggest that chaperone-related dysfunction lies at the etiological root of both ALS and SMA.

Immunoglobulins for intravenous use (IVIgs) and subcutaneous use (SCIgs) can prevent recurrent and severe infections in patients with secondary antibody deficiencies that are frequently linked to haematological/oncological malignancies as well as other clinical conditions and their respective treatments. Even so, as IVIgs and SCIgs are costly and their supply is limited, their clinical use must be optimised. The aim of this position paper is to provide structured practical guidance on the optimal use of IVIgs and SCIgs in secondary antibody deficiencies, particularly in haematological and oncological practice. The authors agree that the occurrence of severe infections is a prerequisite for the use of IVIgs. Serum IgG levels in general as well as IgG subclass levels can be additional indicators of whether a patient could benefit from IVIgs. Responsiveness to vaccines can help to identify immunodeficiency. Patients with chronic lymphocytic leukaemia or multiple myeloma who are receiving respective treatment, especially B-cell depletion therapy, but also some patients with autoimmune diseases are prone to antibody deficiencies and need IVIgs. For the optimal use of IVIgs and to maximise their potential benefit, the indication must be individually assessed for each patient. As a primary treatment goal, the authors define a sufficient prophylaxis of severe infections, which can be supported by normalising IgG levels. If the initiated treatment is insufficient or linked to intolerable adverse reactions, switching the product within the class of IVIgs or changing to a different batch of the same product can be considered. Pausing treatment can also be considered if there are no infections, which happens more frequently in summer, but treatment needs to be resumed once infections return. These structured recommendations for IVIg treatment in patients with secondary antibody deficiency may provide guidance for clinical practice and therefore help to allocate IVIgs to those who will benefit the most, without overusing valuable resources.

Background: The dichotomy between the hypo- versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections. Methods: Using microelectrode recording data collected from the GPi during deep brain stimulation surgery, we compared neuronal spiketrain features between people with PD and those with dystonia, as well as correlated neuronal features with respective clinical scores. Additionally, we characterized and compared readouts of short- and long-term synaptic plasticity using measures of inhibitory evoked field potentials. Results: GPi neurons were slower, burstier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression. Conclusions: We substantiated claims of hyper- versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses. Funding: This project was made possible with the financial support of Health Canada through the Canada Brain Research Fund, an innovative partnership between the Government of Canada (through Health Canada) and Brain Canada, and of the Azrieli Foundation (LM), as well as a grant from the Banting Research Foundation in partnership with the Dystonia Medical Research Foundation (LM).

Background: Orthostatic hypotension (OH) is common in older adults with hypertension. Antihypertensive treatment (AHT) prevents cardio- and cerebrovascular events. However, physicians are concerned to cause OH, making them hesitant to initiate or augment AHT in older adults with hypertension. Methods: We systematically researched electronic databases for trials with older participants (≥65 years) with hypertension and OH assessment after initiating, discontinuing, or augmenting AHT. Study quality was assessed using the ROBINS-I tool. Meta-analyses on OH prevalence and postural blood pressure (BP) drop were performed. Results: Twenty-five studies (26,695 participants) met inclusion criteria, of which fifteen could be included in the meta-analyses. OH prevalence decreased after AHT initiation or augmentation (risk ratio 0.39 (95 % CI = 0.21–0.72; I2 = 47 %; p

Background The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p

Abstract The currently available distribution and range maps for the Great Grey Owl (GGOW; Strix nebulosa) are ambiguous, contradictory, imprecise, outdated, often hand-drawn and thus not quantified, not based on data or scientific. In this study, we present a proof of concept with a biological application for technical and biological workflow progress on latest global open access ‘Big Data’ sharing, Open-source methods of R and geographic information systems (OGIS and QGIS) assessed with six recent multi-evidence citizen-science sightings of the GGOW. This proposed workflow can be applied for quantified inference for any species-habitat model such as typically applied with species distribution models (SDMs). Using Random Forest—an ensemble-type model of Machine Learning following Leo Breiman’s approach of inference from predictions—we present a Super SDM for GGOWs in Alaska running on Oracle Cloud Infrastructure (OCI). These Super SDMs were based on best publicly available data (410 occurrences + 1% new assessment sightings) and over 100 environmental GIS habitat predictors (‘Big Data’). The compiled global open access data and the associated workflow overcome for the first time the limitations of traditionally used PC and laptops. It breaks new ground and has real-world implications for conservation and land management for GGOW, for Alaska, and for other species worldwide as a ‘new’ baseline. As this research field remains dynamic, Super SDMs can have limits, are not the ultimate and final statement on species-habitat associations yet, but they summarize all publicly available data and information on a topic in a quantified and testable fashion allowing fine-tuning and improvements as needed. At minimum, they allow for low-cost rapid assessment and a great leap forward to be more ecological and inclusive of all information at-hand. Using GGOWs, here we aim to correct the perception of this species towards a more inclusive, holistic, and scientifically correct assessment of this urban-adapted owl in the Anthropocene, rather than a mysterious wilderness-inhabiting species (aka ‘Phantom of the North’). Such a Super SDM was never created for any bird species before and opens new perspectives for impact assessment policy and global sustainability.

Abstract Chronic enteropathies (CE) are common disorders in cats and the differentiation between the two main underlying diseases, inflammatory bowel disease (IBD) and low-grade intestinal T-cell lymphoma (LGITL), can be challenging. Characterization of the serum metabolome could provide further information on alterations of disease-associated metabolic pathways and may identify diagnostic or therapeutic targets. Unbiased metabolomics analysis of serum from 28 cats with CE (14 cats with IBD, 14 cats with LGITL) and 14 healthy controls identified 1,007 named metabolites, of which 129 were significantly different in cats with CE compared to healthy controls at baseline. Random Forest analysis revealed a predictive accuracy of 90% for differentiating controls from cats with chronic enteropathy. Metabolic pathways found to be significantly altered included phospholipids, amino acids, thiamine, and tryptophan metabolism. Several metabolites were found to be significantly different between cats with IBD versus LGITL, including several sphingolipids, phosphatidylcholine 40:7, uridine, pinitol, 3,4-dihydroxybenzoic acid, and glucuronic acid. However, random forest analysis revealed a poor group predictive accuracy of 60% for the differentiation of IBD from LGITL. Of 129 compounds found to be significantly different between healthy cats and cats with CE at baseline, 58 remained different following treatment.

Abstract Background Knowledge of the prevalence and attributable burden of headache disorders in India is sparse, with only two recent population-based studies from South and East India. These produced conflicting results. A study in North India is needed. We report the methodology of such a study using, and validating, a Hindi translation of the Headache-Attributed Restriction, Disability, Social Handicap, and Impaired Participation (HARDSHIP) questionnaire developed by Lifting The Burden (LTB). Almost half of the Indian population speak Hindi or one of its dialects. Methods The study adopted LTB’s standardized protocol for population-based studies in a cross-sectional survey using multistage random sampling conducted in urban Delhi and a surrounding rural area. Trained interviewers visited households unannounced, randomly selected one adult member from each and applied the Hindi version of HARDSHIP in face-to-face interviews. The most bothersome headache reported by participants was classified algorithmically into headache on ≥ 15 days/month (H15 +), migraine (including definite and probable) or tension-type headache (including definite and probable). These diagnoses were mutually exclusive. All participants diagnosed with H15 + and a 10% subsample of all others were additionally assessed by headache specialists and classified as above. We estimated the sensitivity and specificity of HARDSHIP diagnoses by comparison with the specialists’ diagnoses. Results From 3,040 eligible households, 2,066 participants were interviewed. The participating proportions were 98.3% in rural areas but 52.9% in urban Delhi. In the validation subsample of 291 participants (149 rural, 142 urban), 61 did not report any headache (seven of those assessed by HARDSHIP, eight by headache specialists and 46 by both) [kappa = 0.83; 95% CI: 0.74-0.91]. In the remaining 230 participants who reported headache in the preceding year, sensitivity, specificity and kappa with (95% CI) were 0.73 (0.65-0.79), 0.80 (0.67-0.90) and 0.43 (0.34-0.58) for migraine; 0.71 (0.56-0.83), 0.80 (0.730.85) and 0.43 (0.37-0.62) for TTH and 0.75 (0.47-0.94), 0.93 (0.89-0.96) and 0.46 (0.34-0.58) for H15 + respectively. Conclusion This study validates the Hindi version of HARDSHIP, finding its performance similar to those of other versions. It can be used to conduct population surveys in other Hindi-speaking regions of India.

Abstract Background Knowledge of headache prevalence, and the burdens attributable to headache disorders, remains incomplete in sub-Saharan Africa (SSA): reliable studies have been conducted only in Zambia (southern SSA) and Ethiopia (eastern SSA). As part of the Global Campaign against Headache, we investigated the prevalence of headache in Cameroon, in Central SSA. Methods We used the same methodology as the studies in Zambia and Ethiopia, employing cluster-randomized sampling in four regions of Cameroon, selected to reflect the country’s geographic, ethnic and cultural diversities. We visited, unannounced, randomly selected households in each region, and randomly selected one adult member (aged 18–65 years) of each. Trained interviewers administered the Headache-Attributed Restriction, Disability and Impaired Participation (HARDSHIP) structured questionnaire, developed by an international expert consensus group and translated into Central African French. Demographic enquiry was followed by diagnostic questions based on ICHD-3 criteria. Results Headache was a near-universal experience in Cameroon (lifetime prevalence: 94.8%). Observed 1-year prevalence of headache was 77.1%. Age- and gender-adjusted estimates were 76.4% (95% confidence interval: 74.9–77.9) for any headache, 17.9% (16.6–19.3) for migraine (definite + probable), 44.4% (42.6–46.2) for tension-type headache (TTH; also definite + probable), 6.5% (5.7–7.4) for probable medication-overuse headache (pMOH) and 6.6% (5.8–7.6) for other headache on ≥ 15 days/month (H15 +). One-day prevalence (“headache yesterday”) was 15.3%. Gender differentials were as expected (more migraine and pMOH among females, and rather more TTH among males). pMOH increased in prevalence until age 55 years, then declined somewhat. Migraine and TTH were both associated with urban dwelling, pMOH, in contrast, with rural dwelling. Conclusions Headache disorders are prevalent in Cameroon. As in Zambia and Ethiopia, estimates for both migraine and TTH exceed global mean estimates. Attributable burden is yet to be reported, but these findings must lead to further research, and measures to develop and implement headache services in Cameroon, with appropriate management and preventative strategies.

Abstract Machine learning (ML) is widely used in classification tasks aimed at detecting various cognitive states or neurological diseases using noninvasive electroencephalogram (EEG) time series. However, successfully detecting specific cognitive skills in a healthy population, independent of subject, remains challenging. This study compared the subject-independent classification performance of three different pipelines: supervised and Riemann projections with logistic regression and handcrafted power spectral features with light gradient boosting machine (LightGBM). 128-channel EEGs were recorded from 26 healthy volunteers while they solved arithmetic, logical, and verbal tasks. The participants were divided into two groups based on their higher education and occupation: specialists in mathematics and humanities. The balanced accuracy of the education type was significantly above chance for all pipelines: 0.84–0.89, 0.85–0.88, and 0.86–0.88 for each type of task, respectively. All three pipelines allowed us to distinguish mathematical proficiency based on learning experience with different trade-offs between performance and explainability. Our results suggest that ML approaches could also be effective for recognizing individual cognitive traits using EEG.

Abstract Species-habitat associations are correlative, can be quantified, and used for powerful inference. Nowadays, Species Distribution Models (SDMs) play a big role, e.g. using Machine Learning and AI algorithms, but their best-available technical opportunities remain still not used for their potential e.g. in the policy sector. Here we present Super SDMs that invoke ML, OA Big Data, and the Cloud with a workflow for the best-possible inference for the 300 + global squirrel species. Such global Big Data models are especially important for the many marginalized squirrel species and the high number of endangered and data-deficient species in the world, specifically in tropical regions. While our work shows common issues with SDMs and the maxent algorithm (‘Shallow Learning'), here we present a multi-species Big Data SDM template for subsequent ensemble models and generic progress to tackle global species hotspot and coldspot assessments for a more inclusive and holistic inference.

Abstract Leptospirosis is a globally distributed zoonotic disease. The standard serological test, known as Microscopic Agglutination Test (MAT), requires the use of live Leptospira strains. To enhance its sensitivity and specificity, the usage of locally circulating strains is recommended. However, to date, no local strain is available from Austria. This study aimed to isolate circulating Leptospira strains from cattle in Austria to enhance the performances of the routine serological test for both humans and animals. We used a statistical approach combined with a comprehensive literature search to profile cattle with greater risk of leptospirosis infection and implemented a targeted sampling between November 2021 and October 2022. Urine and/or kidney tissue were sampled from 410 cattle considered at higher risk of infection. Samples were inoculated into EMJH-STAFF culture media within 2–6 h and a real-time PCR targeting the lipL32 gene was used to confirm the presence/absence of pathogenic Leptospira in each sample. Isolates were further characterised by core genome multilocus sequence typing (cgMLST). Nine out of 429 samples tested positive by PCR, from which three isolates were successfully cultured and identified as Leptospira borgpetersenii serogroup Sejroe serovar Hardjobovis, cgMLST cluster 40. This is the first report on the isolation and genotyping of local zoonotic Leptospira in Austria, which holds the potential for a significant improvement in diagnostic performance in the country. Although the local strain was identified as a cattle-adapted serovar, it possesses significant zoonotic implications. Furthermore, this study contributes to a better understanding of the epidemiology of leptospirosis in Europe.

Abstract The present study investigated primary care patients and compared self-reported sexual health in Swedes and Middle Easterners; analysed differences within and between the groups and analysed differences in 25-hydroxyvitamin D [25(OH)D] levels between the groups. 522 patients responded to a health questionnaire that included items on sexual health: 225 Middle Easterners from Iran, Iraq, and Turkey and 297 Swedes. Logistic regression was used to calculate the odds ratio (OR). Middle Easterners reported less sexual dysfunction than Swedes, and 75.8% of them and 18.9% of Swedes presented a 25(OH)D of

Abstract The World Health Organization (WHO) Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders was developed by WHO to address the worldwide challenges and gaps in provision of care and services for people with epilepsy and other neurological disorders and to ensure a comprehensive, coordinated response across sectors to the burden of neurologic diseases and to promote brain health across life-course. Headache disorders constitute the second most burdensome of all neurological diseases after stroke, but the first if young and midlife adults are taken into account. Despite the availability of a range of treatments, disability associated with headache disorders, and with migraine, remains very high. In addition, there are inequalities between high-income and low and middle income countries in access to medical care. In line with several brain health initiatives following the WHOiGAP resolution, herein we tailor the main pillars of the action plan to headache disorders: (1) raising policy prioritization and strengthen governance; (2) providing effective, timely and responsive diagnosis, treatment and care; (3) implementing strategies for promotion and prevention; (4) fostering research and innovation and strengthen information systems. Specific targets for future policy actions are proposed. The Global Action Plan triggered a revolution in neurology, not only by increasing public awareness of brain disorders and brain health but also by boosting the number of neurologists in training, raising research funding and making neurology a public health priority for policy makers. Reducing the burden of headache disorders will not only improve the quality of life and wellbeing of people with headache but also reduce the burden of neurological disorders increasing global brain health and, thus, global population health.