Miracle-dz/UniFAR-FTUs huggingface dataset:
4-Hydroxypiperidines and Their Flexible 3-(Amino)propyloxy Analogues as Non-Imidazole Histamine H3 Receptor Antagonist: Further Structure–Activity Relationship Exploration and In Vitro and In Vivo Pharmacological Evaluation

Presynaptic histamine H3 receptors (H3R) act as auto- or heteroreceptors controlling, respectively, the release of histamine and of other neurotransmitters in the central nervous system (CNS). The extracellular levels of several neurotransmitters are enhanced by H3R antagonists, and there is a great interest for potent, brain-penetrating H3 receptor antagonists/inverse agonists to compensate for the neurotransmitter deficits present in various neurological disorders. We have shown that 1-[(benzylfuran-2-yl)methyl]piperidinyl-4-oxyl- and benzyl- derivatives of N-propylpentan-1-amines exhibit high in vitro potencies toward the guinea pig H3 receptor (jejunum), with pA2 = 8.47 and 7.79, respectively (the reference compound used was thioperamide with pA2 = 8.67). Furthermore, following the replacement of 4-hydroxypiperidine with a 3-(methylamino)propyloxy chain, the pA2 value for the first group decreased, whereas it increased for the second group. Here, we present data on the impact of elongating the aliphatic chain between the nitrogen of 4-hydroxypiperidine or 3-(methylamino)propan-1-ol and the lipophilic residue. Additionally, the most active compound in this series of non-imidazole H3 receptor antagonists/inverse agonists, i.e., ADS-003, was evaluated for its affinity to the recombinant rat and human histamine H3 receptors transiently expressed in HEK-293T cells. It was shown that ADS-003, given parenterally for 5 days, reduced the food intake of rats, as well as changed histamine and noradrenaline concentrations in the rats’ brain in a manner and degree similar to the reference H3 antagonist Ciproxifan.
Symptoms of prolonged grief and posttraumatic stress following loss: A latent class analysis

Objective: Individuals vary in how they respond to bereavement. Those who experience poor bereavement outcomes often report symptoms from more than one diagnostic category. This study sought to identify groups of individuals who share similar patterns of prolonged grief disorder and posttraumatic stress disorder symptoms to determine whether these profiles are differentially related to negative appraisals thought to contribute to prolonged grief disorder and posttraumatic stress disorder symptomatology. Methods: Participants were 185 bereaved adults. Latent class analysis was used to identify subgroups of individuals who showed similar patterns of co-occurrence of prolonged grief disorder and posttraumatic stress disorder symptoms. Multinomial regression was used to examine the extent to which appraisal domains and sociodemographic and loss factors predicted class membership. Results: Latent class analysis revealed three classes of participants: a low symptom group, a high prolonged grief disorder symptom group, and a high prolonged grief disorder and posttraumatic stress disorder symptom group. Membership of the prolonged grief disorder group and prolonged grief disorder and posttraumatic stress disorder group was predicted by higher mean negative self-related appraisals. Demographic and loss-related factors did not predict group membership. Conclusion: These findings have implications for understanding co-occurrence of prolonged grief disorder and posttraumatic stress disorder symptoms following bereavement. Findings are consistent with theoretical models highlighting the importance of negative self-related beliefs in prolonged grief disorder.
The Association between Quality of HIV Care, Loss to Follow-Up and Mortality in Pediatric and Adolescent Patients Receiving Antiretroviral Therapy in Nigeria

Access to pediatric HIV treatment in resource-limited settings has risen significantly. However, little is known about the quality of care that pediatric or adolescent patients receive. The objective of this study is to explore quality of HIV care and treatment in Nigeria and to determine the association between quality of care, loss-to-follow-up and mortality. A retrospective cohort study was conducted including patients ≤18 years of age who initiated ART between November 2002 and December 2011 at 23 sites across 10 states. 1,516 patients were included. A quality score comprised of 6 process indicators was calculated for each patient. More than half of patients (55.5%) were found to have a high quality score, using the median score as the cut-off. Most patients were screened for tuberculosis at entry into care (81.3%), had adherence measurement and counseling at their last visit (88.7% and 89.7% respectively), and were prescribed co-trimoxazole at some point during enrollment in care (98.8%). Thirty-seven percent received a CD4 count in the six months prior to chart review. Mortality within 90 days of ART initiation was 1.9%. A total of 4.2% of patients died during the period of follow-up (mean: 27 months) with 19.0% lost to follow-up. In multivariate regression analyses, weight for age z-score (Adjusted Hazard Ratio (AHR): 0.90; 95% CI: 0.85, 0.95) and high quality indicator score (compared a low score, AHR: 0.43; 95% CI: 0.26, 0.73) had a protective effect on mortality. Patients with a high quality score were less likely to be lost to follow-up (Adjusted Odds Ratio (AOR): 0.42; 95% CI: 0.32, 0.56), compared to those with low score. These findings indicate that providing high quality care to children and adolescents living with HIV is important to improve outcomes, including lowering loss to follow-up and decreasing mortality in this age group.
What We Know About the Brain Structure–Function Relationship

How the human brain works is still a question, as is its implication with brain architecture: the non-trivial structure–function relationship. The main hypothesis is that the anatomic architecture conditions, but does not determine, the neural network dynamic. The functional connectivity cannot be explained only considering the anatomical substrate. This involves complex and controversial aspects of the neuroscience field and that the methods and methodologies to obtain structural and functional connectivity are not always rigorously applied. The goal of the present article is to discuss about the progress made to elucidate the structure–function relationship of the Central Nervous System, particularly at the brain level, based on results from human and animal studies. The current novel systems and neuroimaging techniques with high resolutive physio-structural capacity have brought about the development of an integral framework of different structural and morphometric tools such as image processing, computational modeling and graph theory. Different laboratories have contributed with in vivo, in vitro and computational/mathematical models to study the intrinsic neural activity patterns based on anatomical connections. We conclude that multi-modal techniques of neuroimaging are required such as an improvement on methodologies for obtaining structural and functional connectivity. Even though simulations of the intrinsic neural activity based on anatomical connectivity can reproduce much of the observed patterns of empirical functional connectivity, future models should be multifactorial to elucidate multi-scale relationships and to infer disorder mechanisms.
Habitat‐dependent reduction of sexual dimorphism in geometric body shape of Haida Gwaii threespine stickleback

We investigated the extent of sexual dimorphism in body shape in adult threespine stickleback (Gasterosteus aculeatus) from 39 lakes, eight streams, and five marine (two brackish, three full marine) localities on the Haida Gwaii archipelago off the mid-coast of British Columbia, as well as three lakes from southern British Columbia with benthic–limnetic species pairs. Based on digital images of 709 males and 593 females, body shape was quantified using discriminant function analysis on partial warp scores generated from twelve homologous landmarks. All populations showed males with higher positive values for canonical vector 1, which are characterized by larger heads, larger gape, posteriad dorsal spines, posteriad pelvis, longer anal fin, and deep posterior caudal depth relative to those in females. Geographical variability was present, with the highest dimorphism occurring in two of the marine habitats in addition to large lakes, whereas reduced dimorphism occurs in small shallow dystrophic ponds. We suggest that this reduction is the derived condition and is primarily due to loss of niche breadth and convergence in body shape between the sexes in pond habitats. Analyses of two experimental pond populations indicate that up to 15% of the shape dimorphism can be attributed to habitat-induced phenotypic plasticity. © 2008 The Linnean Society of London, Biological Journal of the Linnean Society, 2008, 95, 505–516.
New York City House Mice (Mus musculus) as Potential Reservoirs for Pathogenic Bacteria and Antimicrobial Resistance Determinants

ABSTRACT House mice (Mus musculus) thrive in large urban centers worldwide. Nonetheless, little is known about the role that they may play in contributing to environmental contamination with potentially pathogenic bacteria. Here, we describe the fecal microbiome of house mice with emphasis on detection of pathogenic bacteria and antimicrobial resistance genes by molecular methods. Four hundred sixteen mice were collected from predominantly residential buildings in seven sites across New York City over a period of 13 months. 16S rRNA sequencing identified Bacteroidetes as dominant and revealed high levels of Proteobacteria. A targeted PCR screen of 11 bacteria, as indicated by 16S rRNA analyses, found that mice are carriers of several gastrointestinal disease-causing agents, including Shigella, Salmonella, Clostridium difficile, and diarrheagenic Escherichia coli. Furthermore, genes mediating antimicrobial resistance to fluoroquinolones (qnrB) and β-lactam drugs (blaSHV and blaACT/MIR) were widely distributed. Culture and molecular strain typing of C. difficile revealed that mice harbor ribotypes associated with human disease, and screening of kidney samples demonstrated genetic evidence of pathogenic Leptospira species. In concert, these findings support the need for further research into the role of house mice as potential reservoirs for human pathogens and antimicrobial resistance in the built environment. IMPORTANCE Mice are commensal pests often found in close proximity to humans, especially in urban centers. We surveyed mice from seven sites across New York City and found multiple pathogenic bacteria associated with febrile and gastrointestinal disease as well as an array of antimicrobial resistance genes. Mice are commensal pests often found in close proximity to humans, especially in urban centers. We surveyed mice from seven sites across New York City and found multiple pathogenic bacteria associated with febrile and gastrointestinal disease as well as an array of antimicrobial resistance genes.
Riverine discharges impact physiological traits and carbon sources for shell carbonate in the marine intertidal mussel Perumytilus purpuratus

Anthropogenic modification watersheds and climate change have altered export from fluvial systems causing changes to the carbonate chemistry of river‐influenced near shore environments. To determine the possible effects of riverine discharges on the mussel Perumytilus purpuratus, we performed in situ transplant experiments between river‐influenced and open coastal habitats with contrasting seawater carbonate chemistries (i.e., pCO2, pH, Ωar) across four regions covering a wide latitudinal range (32°55′S–40°10′S). The river‐influenced habitats selected for transplant experiments were different than open coastal habitats; with higher pCO2 (354–1313 μatm), lower pH (7.6–7.9) and Ωar values (0.4–1.4) than in open coastal area. Growth, calcification, metabolism were measured in a reciprocal transplant experiment to determine physiological responses associated with river‐influenced sites and non‐influenced control sites. Growth and calcification rates were higher in river‐influenced habitats; however the organisms in this area also had lower metabolic rates, possibly due to enhanced food supply from river systems. Further analysis of carbon isotopic composition (δ13C) indicated that the relative contribution of seawater dissolved inorganic carbon (DIC) to the carbonate shells of P. purpuratus was much higher than respiratory carbon. Nevertheless, P. purpuratus incorporated between 7% and 26% of metabolic carbon in the shell depending on season. There was a strong, significant relationship between δ13CPOC and δ13CTissue, which likely influenced the isotopic composition of the shell carbon.
Atorvastatin and Thrombogenicity of the Carotid Atherosclerotic Plaque: the ATROCAP Study

Summary Statins appear to have beneficial effects on fibrous cap stabilisation but their effects on plaque thrombogenicity have not been reported. To evaluate the thrombogenicity of human carotid plaques before and after atorvastatin treatment, 59 patients with bilateral carotid stenosis eligible for two-step carotid endoarterectomy (CEA) were randomly assigned to atorvastatin, 20 mg/day, or placebo. Histological and immunohistochemical analyses, Tissue Factor (TF), Tissue Factor Pathway Inhibitor (TFPI) antigens (Ag) and TF activity were determined in endoarterectomy specimens obtained at baseline and after treatment. Mean TFAg and TFPIAg levels from plaques removed at the first CEA were 55 ± 56 and 32 ± 26 pg/mg. After placebo, TFAg and TFPIAg content was higher in the second than the first CEA. Plaques removed at the second CEA from atorvastatin-treated patients had a lower macrophage content than plaques at the first CEA. TFAg and TFPIAg levels, and TF activity in plaques after atorvastatin treatment were lower (respectively 29, 18% and 56%) than after placebo. These findings indicate that atorvastatin reduce the inflammatory/thrombotic phenotype of carotid plaque, suggesting that these drugs may indeed have a beneficial effect on cerebrovascular events. We are indebted to Pfizer Italia for providing atorvastatin, 20 mg, and placebo.
Luminescence Dating of Fluvial Deposits from the Weser Valley, Germany

Abstract Luminescence dating was applied on coarse-grained monomineralic potassium-rich feld-spar and polymineralic fine-grained minerals of five samples derived from fluvial deposits of the Riv-er Weser in northwestern Germany. We used a pulsed infrared stimulated luminescence (IRSL) single aliquot regenerative (SAR) dose protocol with an IR stimulation at 50°C for 400 s (50 μs on-time and 200 μs off-time). In order to obtain a stable luminescence signal, only off-time IRSL signal was rec-orded. Performance tests gave solid results. Anomalous fading was intended to be reduced by using the pulsed IRSL signal measured at 50°C (IR50), but fading correction was in most cases necessary due to moderate fading rates. Fading uncorrected and corrected pulsed IR50 ages revealed two major fluvial aggradation phases during the Late Pleistocene, namely during marine isotope stage (MIS) 5d (100 ± 5 ka) and from late MIS 5b to MIS 4 (77 ± 6 ka to 68 ± 5 ka). The obtained luminescence ages are consistent with previous 230Th/U dating results from underlying interglacial deposits of the same pit, which are correlated with MIS 7c to early MIS 6.
Neural systems underlying affective disorders

Three main approaches are used to explore the neural correlates of mood disorder: neuropsychological studies, neuroimaging studies and post-mortem investigations. Lesion studies implicate disturbances in the frontal lobe, basal ganglia, striatum and anterior temporal cortex. Early neurocognitive and neuropathological investigations led to a 'hypofrontality' hypothesis of unipolar and bipolar depression, but functional neuroimaging has revealed a more complex picture. Thus, increased metabolism may occur in the subgenual anterior cingulate gyrus in resting-state studies of depression and sad-mood induction. Antidepressants may reduce this activity. Amygdala hyperactivation also is associated with affective disorders. Task-related studies reveal abnormal biases in memory, the experience of pleasure and the perception of emotional facial expressions. There is still little clarity whether the abnormalities in brain activation represent state or trait characteristics of affective disorders. famously suffered from accidental damage of the frontal lobe in 1848. The iron bar that forced its way through his cranium caused lesions in the left and right ventromedial regions of the pre- frontal cortex (as reconstructed by Damasio et al, 1994). Mr Gage, who was an exemplary citizen before the accident, afterwards became a com- pletely different person - impatient, rude and prone to outbursts of anger and rage. Blumer & Benson (1975) proposed that personality changes after frontal lobe damage could be classified under 'pseudopsychopathy' or 'pseudodepression'.
Therapeutic Efficacy of Endometrial Scratching in Repeated Controlled Ovarian Stimulation (COS) Failure Cycles

Objective: The objective of the study was (1) “to evaluate the therapeutic efficacy of endometrial scratching in repeated controlled ovarian stimulation (COS) failure cycles. ” And (2) “to compare differences in pregnancy outcome by endometrial scratching in early (D2–D4) and late follicular phases (D7–D9) of the same stimulation cycle. ” Materials and Methods: Women attending infertility clinic in a tertiary care center and who have two or more repeated COS failure cycles and planned for COS with intrauterine insemination (IUI) were included in the study which is a prospective parallel, interventional, single-blinded, randomized control study, in 1:1 allocation ratio. A total of 165 patients were recruited and randomly allocated into three groups: Group A (n = 55) underwent endometrial scratching on D2–D4 of the same COS cycle, Group B (n = 55) on D7–D9, and Group C (n = 55) no intervention done. All the patients underwent COS according to standard protocol followed by IUI. Results: Clinical pregnancy rate was 12.73% (odds ratio [OR] =0.87 95% confidence interval [CI] =0.288–2.55, P = 1), 16.36% (OR = 1.15; 95% CI = 0.40–3.23, P = 1), and 14.54%, respectively, in Group A, B, and C, respectively (P = 0.86), as per intention to treat analysis. Using Chi-square test, P value between Group A and B was 0.787, between Group A and C was 1.000, and between Group B and C was 1.000. As per protocol analysis, clinical pregnancy rate was 13.46% (OR = 0.83; 95% CI = 0.27–2.5, P = 0.74), 19.57% (OR = 1.3 95%; CI = 0.45–3.73, P = 0.41), and 15.69%. Using Chi-square test, P value between Group A and B was 0.588, between Group A and C was 0.967, and between Group B and C was 0.815. No abortions and multiple pregnancies occurred in either of the groups. Conclusion: The effect found was of good quantum in Group B as per protocol analysis which could be of clinical relevance if larger sample size would have been taken. Endometrial scratching is a cost-effective and easy technique which may improve clinical pregnancy rates in previous COS failure cycles, but more trials are needed to be conducted using larger sample size to achieve the improved and significant outcome.
A Mobile Health App–Based Postnatal Educational Program (Home-but not Alone): Descriptive Qualitative Study

Background The postnatal period poses numerous challenges for new parents. Various educational programs are available to support new parents during this stressful period. However, the usefulness of educational programs must be evaluated to ascertain their credibility. Objective The aim of this descriptive, qualitative study was to explore the views of parents of newborns with regard to the content and delivery of a mobile health (mHealth) app–based postnatal educational program. Methods A qualitative semistructured interview guide was used to collect data from 17 participants who belonged to the intervention group of a randomized controlled trial. The intervention, a 4-week-long access to a mHealth app–based educational program, was evaluated. The interviews were conducted in English and at the participants’ homes. Thematic analysis was used to analyze the data. The Consolidated Criteria for Reporting Qualitative Research checklist was used to report the findings. Results The interviews revealed 4 main themes: (1) positive features of the mHealth app, (2) advice from midwives, (3) experiences gained from using the mHealth app, and (4) recommendations for the future. The participants evaluated the educational program to be a good source of information that was tailored to the local context. The different modes of delivery, including audio and video, accentuated the accessibility of information. The parents evaluated that the facilitator of the featured communication platform, a midwife, provided trustworthy advice. Belongingness to a virtual community beyond the hospital endowed the parents the confidence that they were not alone and were supported by other parents and health care professionals. Conclusions According to the parents, the mHealth app–based educational program was helpful in supporting a multi-ethnic sample of parents during the postnatal period. This insight indicates that the program could be implemented in a wide community of parents in the postnatal period. The helpfulness of the educational program is a testament of the potential benefits of using telemedicine among new parents postnatally. Resources can also be dedicated toward extending the duration of access to the app beyond 1 month and developing relevant content for parents across the perinatal period.
Committed Action, Disability and Perceived Health in Individuals with Fibromyalgia

ABSTRACT Committed action, one of the components of psychological flexibility, has been shown to be related with measures of pain-relevant function domains in patients with chronic pain. However, the associations between measures of committed action and of physical health and function in individuals with fibromyalgia (FM) have not yet been examined. The aim of the present cross-sectional study was to better understand the role that committed action plays in (1) pain-related disability and (2) mental and physical health in individuals with FM. One hundred twenty-nine adult females with a diagnosis of FM from a rheumatologist were administered measures of committed action, disability, physical health, and mental health. After controlling for age and pain intensity, committed action explained an additional 24% of the variance of pain disability, 39% of the variance of physical health, and 41% of the variance of mental health. This study provides important new information on the associations between a measure of committed action and perceived health and function in a sample of women with FM. The findings are also consistent with the psychological flexibility model for understanding pain and its impact in patients with FM.