Miracle-dz/UniFAR-FTUs huggingface dataset:
Facteurs associés à la mortalité maternelle intra-hospitalière et circonstances de décès chez des femmes avec complications obstétricales sévères à Kinshasa (RDCongo)

Worldwide, more than half a million of women die every year of pregnancy or delivery-related complications. Awareness about this important public health problem increased after the launch of the Safe Motherhood Initiative in Nairobi in 1987; since then, various programmes have been initiated by international agencies to address the problem. North-South differences in maternal mortality are still high and the highest of the current public health indicators with levels being 100 times higher in several developing countries and especially in Sub-Saharan Africa. Maternal mortality is very high in Kinshasa, the D.R. Congo capital city, despite its numerous health services, the number of health professionals and the high rate of maternal health services’ use. A case-control survey was organised in 2004 to identify the risk factors associated to maternal death and the circumstances where serious obstetrical complications or maternal deaths occur. The case-control study design compared each selected maternal death with two surviving women having had a similar obstetrical complication. Maternal deaths were identified over a 12 month period (January to December 2004) in twelve reference maternity wards in Kinshasa There were 110 case (maternal deaths) and 208 controls. Information was gathered by interviewing family members of the deceased and surviving women and from hospitals registers. Unadjusted and adjusted OR and 95% CI were estimated with SPSS version 14. Multivariate analysis showed the negative effect of excessive referrals and the protective effect of the following: having a paid activity, beginning the health services use itinerary in the referral maternity and having used antenatal care. The most common observed shortage of basic equipment in the surveyed maternities were the lack of blood (transfusion) or of oxygen. In a health system without insurance or any other solidarity mechanism, the lack of money is a real problem to access to health services. Short-term objectives would have been to initiate a costs division mechanism or to subsidy expenses linked to delivery and long-term, to prepare a national health insurance scheme able to provide a sufficient health coverage for the members or users. Our results underline the importance of improving the access to essential obstetrical care during pregnancy and delivery.
Cambios en las variables antropométricas durante la gestación en mujeres eutróficas

: To analyze the behavior of the anthropometric measures during gestation in teenagers and adults pregnant women. The study group was formed by 81 well nourished, healthy pregnant women, 14 teenagers and 67 adults. They were evaluated at Centro de Atencion Nutricional Infantil "Antimano". The anthropometric criteria included at least five anthropometric evaluations: one in the first trimester of pregnancy, two in the second and two in the third. The anthropometric variable mean was obtained from each one of the pregnant women in each of their corresponding visits during the first, second and third trimester. The descriptive statistics of the studied anthropometric variables were calculated. Student' t test was applied. There were significant changes during pregnancy in weight, wrist, waist, abdomen, waist-hip, hip-gluteal, thigh and calf circumferences and body mass index in teenagers and adults. There were significant changes during gestation in a lying down position height in teenagers and mid-arm circumference in adults. There was significant difference in change from the first to the third trimester of gestation, between teenagers and adults in the calf circumference. The studied anthropometric variables presented the same behavior during gestation in adolescents and adults, unless the mid-upper arm circumference.
A Rapid Interference between Glucocorticoids and cAMP‐Activated Signalling in Hypothalamic Neurones Prevents Binding of Phosphorylated cAMP Response Element Binding Protein and Glucocorticoid Receptor at the CRE‐Like and Composite GRE Sites of Thyrotrophin‐Releasing Hormone Gene Promoter

Glucocorticoids or cAMP increase, within minutes, thyrotrophin‐releasing hormone (TRH) transcription in hypothalamic primary cultures, although this effect is prevented if cells are simultaneously incubated with both drugs. Rat TRH promoter contains a CRE site at −101/−94 bp and a composite GRE element (cGRE) at −218/−197 bp. Nuclear extracts of hypothalamic cells incubated with 8Br‐cAMP or dexamethasone, and not their combination, bind to oligonucleotides containing the CRE or cGRE sequences. Adjacent to CRE are Sp/Krüppel response elements, and flanking the GRE half site, two AP1 binding sites. The present study aimed to identify the hypothalamic transcription factors that bind to these sites. We verified that the effects of glucocorticoid were not mimicked by corticosterone‐bovine serum albumin. Footprinting and chromatin immunoprecipitation (ChIP) assays were used to examine the interaction of cAMP‐ and glucocorticoid‐mediated regulation of TRH transcription at the CRE and cGRE regions of the TRH promoter. Nuclear extracts from hypothalamic cells incubated for 1 h with cAMP or glucocorticoids protected CRE. The GRE half site was recognised by nuclear proteins from cells stimulated with glucocorticoids and, for the adjacent AP‐1 sites, by nuclear proteins from cells stimulated with cAMP or phorbol esters. Protection of CRE or cGRE was lost if cells were coincubated with dexamethasone and 8Br‐cAMP. ChIP assays revealed phospho‐CREB, c‐Jun, Sp1, c‐Fos and GR antibodies bound the TRH promoter of cells treated with cAMP or glucocorticoids; anti:RNA‐polymerase II immunoprecipitated TRH promoter in a similar proportion as anti:pCREB or anti:GR. Recruitment of pCREB, SP1 or GR was lost when cells were exposed simultaneously to 8Br‐cAMP and glucocorticoids. The data show that while pCREB and Sp1 bind to CRE‐2, or GR to cGRE of the TRH promoter, the mutual antagonism between cAMP and glucocorticoid signalling, which prevent their binding to TRH promoter, could serve as a mechanism by which glucocorticoids rapidly suppress cAMP and noradrenaline‐stimulated TRH transcription.
Prenatal Exposure to Vinclozolin Disrupts Selective Aspects of the Gonadotrophin‐Releasing Hormone Neuronal System of the Rabbit

Developmental exposure to the agricultural fungicide vinclozolin can impair reproductive function in male rabbits and was previously found to decrease the number of immunoreactive‐gonadotrophin‐releasing hormone (GnRH) neurones in the region of the organum vasculosum of the lamina terminalis and rostral preoptic area by postnatal week (PNW) 6. In the present study, in an aim to further examine the disruption of GnRH neurones by foetal vinclozolin exposure, pregnant rabbits were dosed orally with vinclozolin, flutamide or carrot paste vehicle for the last 2 weeks of gestation. Offspring were euthanised at birth (males and females), PNW 6 (females), PNW 26 (adult males) or PNW 30 (adult females) of age. At birth and in adults, brains were sectioned and processed for immunoreactive GnRH. The numbers of immunoreactive GnRH neuronal perikarya were significantly decreased in vinclozolin‐treated rabbits at birth and in adult littermates. By contrast, there was an increase in GnRH immunoreactivity in the terminals in the region of the median eminence. Analysis of PNW 6 female brains by radioimmunoassay revealed a two‐fold increase in GnRH peptide content in the mediobasal hypothalamus in vinclozolin‐treated rabbits. This finding was complemented by immunofluorescence analyses, which revealed a 2.8‐fold increase in GnRH immunoreactivity in the median eminence of vinclozolin compared to vehicle‐treated females at PNW 30. However, there was no difference between treatment groups in the measures of reproduction that were evaluated: ejaculation latency, conception rates or litter size. These results indicate that sub‐acute, prenatal vinclozolin treatment is sufficient to create perdurable alterations in the GnRH neuronal network that forms an important input into the reproductive axis. Finally, the effect of vinclozolin on the GnRH neuronal network was not comparable to that of flutamide, suggesting that vinclozolin was not acting through anti‐androgenic mechanisms.
Liver transplantation for mitochondrial neurogastrointestinal encephalomyopathy

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a fatal, recessive disease caused by mutations in the gene encoding thymidine phosphorylase, leading to reduced enzymatic activity, toxic nucleoside accumulation, and secondary mitochondrial DNA damage. Thymidine phosphorylase replacement has been achieved by allogeneic hematopoietic stem cell transplantation, a procedure hampered by high mortality. Based on high thymidine phosphorylase expression in the liver, a 25‐year‐old severely affected patient underwent liver transplantation. Serum levels of toxic nucleosides rapidly normalized. At 400 days of follow‐up, the patient's clinical conditions are stable. We propose liver transplantation as a new therapy for MNGIE. Ann Neurol 2016;80:448–455
Brain Stem Catecholamines Circuitry: Activation by Alcohol and Role in the Hypothalamic‐Pituitary‐Adrenal Response to this Drug

Although the stimulatory effect of alcohol on the rat hypothalamic‐pituitary‐adrenal (HPA) axis is well known, the mechanisms underlying this influence remain poorly understood. In the present study, we tested the hypothesis that brain catecholamines play an important role in this response. As expected, the acute intragastric administration of alcohol to adult male rats elevated plasma adrenocorticotrophic hormone (ACTH) levels and activated hypothalamic corticotrophin‐releasing factor neurones. Novel findings pertain to the effect of alcohol on, and the role played by, brain adrenergic circuits. We first observed that alcohol up‐regulated c‐fos signals in the locus coeruleus, the main noradrenergic brain cell group; and that it activated (nor)adrenergic medullary cells (A1–A2/C1–C3). Evidence for the role played by these catecholaminergic circuits then came from the observation that blockade of α1‐, but not β‐, adrenergic receptors interfered with alcohol‐induced ACTH secretion; and that depletion of catecholaminergic input to the paraventricular nucleus (PVN) by the toxin 6‐hydroxydopamine significantly decreased the ACTH response to alcohol. Finally, destruction of the A1–A2/C1–C3 region with the immunotoxin anti‐dopamine‐B‐hydroxylase‐saporin interfered with the catecholaminergic input to the PVN. Collectively, our work extends our knowledge of the ability of this drug to up‐regulate catecholamine circuitry in the rat brain. It also shows that medullary catecholamine innervation of the hypothalamus plays an important role in modulating the stimulatory effect of alcohol on the HPA axis, an effect exerted through activation of α1‐adrenergic receptors.
German government breaks off talks with doctors

The German health minister, Andrea Fischer, of Germany's Green party, has had enough. Last week she declared that she will not discuss any further her proposed health reform with representatives from the Kassenarztliche Bundesvereinigung. Members of the organisation (which represents 110 000 non-hospital doctors), who treat patients insured with Germany's various insurance companies, were once more questioning the compromise that the ministry and their organisation had reached on the drugs budget (28 August, p 536). Under the reform, the government has …
Intramolecular Interactions between the Dbl Homology (DH) Domain and the Carboxyl-terminal region of Myosin II-interacting Guanine Nucleotide Exchange Factor (MyoGEF) Act as an Autoinhibitory Mechanism for the Regulation of MyoGEF Functions*

Background: MyoGEF is implicated in regulating cytokinesis and breast cancer cell invasion. Results: Binding of the MyoGEF carboxyl-terminal region to its DH domain suppresses breast cancer cell invasion and interferes with cytokinesis. Conclusion: Intramolecular interactions of MyoGEF act as an autoinhibitory mechanism to regulate MyoGEF functions. Significance: Autoinhibitory intramolecular interactions of MyoGEF serve as a control point to regulate cytokinesis and breast cancer cell invasion. We have reported previously that nonmuscle myosin II-interacting guanine nucleotide exchange factor (MyoGEF) plays an important role in the regulation of cell migration and cytokinesis. Like many other guanine nucleotide exchange factors (GEFs), MyoGEF contains a Dbl homology (DH) domain and a pleckstrin homology domain. In this study, we provide evidence demonstrating that intramolecular interactions between the DH domain (residues 162–351) and the carboxyl-terminal region (501–790) of MyoGEF can inhibit MyoGEF functions. In vitro and in vivo pulldown assays showed that the carboxyl-terminal region (residues 501–790) of MyoGEF could interact with the DH domain but not with the pleckstrin homology domain. Expression of a MyoGEF carboxyl-terminal fragment (residues 501–790) decreased RhoA activation and suppressed actin filament formation in MDA-MB-231 breast cancer cells. Additionally, Matrigel invasion assays showed that exogenous expression of the MyoGEF carboxyl-terminal region decreased the invasion activity of MDA-MB-231 cells. Moreover, coimmunoprecipitation assays showed that phosphorylation of the MyoGEF carboxyl-terminal region by aurora B kinase interfered with the intramolecular interactions of MyoGEF. Furthermore, expression of the MyoGEF carboxyl-terminal region interfered with RhoA localization during cytokinesis and led to an increase in multinucleation. Together, our findings suggest that binding of the carboxyl-terminal region of MyoGEF to its DH domain acts as an autoinhibitory mechanism for the regulation of MyoGEF activation.
Chemotherapy‐induced peripheral neuropathy: A current review

Chemotherapy‐induced peripheral neuropathy (CIPN) is a common dose‐limiting side effect experienced by patients receiving treatment for cancer. Approximately 30 to 40% of patients treated with neurotoxic chemotherapy will develop CIPN, and there is considerable variability in its severity between patients. It is often sensory‐predominant with pain and can lead to long‐term morbidity in survivors. The prevalence and burden of CIPN late effects will likely increase as cancer survival rates continue to improve. In this review, we discuss the approach to peripheral neuropathy in patients with cancer and address the clinical phenotypes and pathomechanisms of specific neurotoxic chemotherapeutic agents. Ann Neurol 2017;81:772–781
Nesfatin‐1 Suppresses Energy Intake, Co‐localises Ghrelin in the Brain and Gut, and Alters Ghrelin, Cholecystokinin and Orexin mRNA Expression in Goldfish

Nesfatin‐1 is a novel anorectic peptide encoded in the precursor protein nucleobindin‐2 (NUCB2). We recently reported the presence and appetite suppressing effects of nesfatin‐1 in goldfish. Nesfatin‐1 has been co‐localised with ghrelin in the stomach of rats. Whether nesfatin‐1 influences other appetite regulatory peptides in goldfish remains unclear. The main objectives of the present study were to investigate whether nesfatin‐1 co‐localises ghrelin in goldfish, and to test whether exogenous nesfatin‐1 influences endogenous ghrelin, cholecystokinin (CCK) and orexin A (OXA). We found co‐localisation of nesfatin‐1‐like and ghrelin‐like immunoreactivity in the enteroendocrine cells of the goldfish anterior intestine (J‐loop). Furthermore, co‐localisation of ghrelin and nesfatin‐1 was also observed in the posterior nucleus lateralis tuberis of the goldfish hypothalamus, a brain region implicated in the regulation of food intake. These findings suggest a functional relationship between ghrelin and nesfatin‐1 in goldfish. In support of this, i.c. v. administration of goldfish (gf) nesfatin‐1 [25 ng/g body weight (BW)], suppressed food intake and the expression of mRNAs encoding preproghrelin, ghrelin receptor (GHS‐R 1a‐1), CCK and NUCB2 in the forebrain of fed fish, as well as ghrelin and NUCB2 mRNA in the hypothalamus of unfed fish, both at 1 h post‐injection. Nesfatin‐1 stimulated hypothalamic CCK mRNA expression at 30 min post‐injection in fed fish, and inhibited OXA mRNA in the unfed fish hypothalamus 1 h post‐injection. Similarly, i.c. v. injections of gfghrelin (1 ng/g BW), although stimulating food intake, suppressed NUCB2 and preproghrelin mRNAs, but not ghrelin receptor mRNA expression in the forebrain. It is also evident that exogenous ghrelin and nesfatin‐1 mRNAs encoding these peptides. Our novel results indicate interactions between nesfatin‐1 and ghrelin, CCK and orexin, and show that nesfatin‐1 acts on other appetite regulatory peptides in a time‐ and feeding status‐dependent, as well as tissue‐specific, manner in goldfish.
Actin Cytoskeleton Remodelling by Sex Steroids in Neurones

Cell morphology and its interaction with the extracellular environment are integrated processes involving a number of intracellular controllers orchestrating cytoskeletal proteins and their interaction with the cell membrane and anchorage proteins. Sex steroids are effective regulators of cell morphology and tissue organisation, and recent evidence indicates that this is obtained through the regulation of the actin cytoskeleton. Intriguingly, many of these regulatory actions related to cell morphology are achieved through the rapid, nonclassical signalling of sex steroid receptors to kinase cascades, independently from nuclear alteration of gene expression or protein synthesis. The identification of the mechanistic basis for these rapid actions on cell cytoskeleton has special relevance for the characterisation of the effects of sex steroids under physiological conditions, such as for the development of neurone/neurone interconnections and dendritic spine density. This is considered to be critical for gender‐specific differences in brain function and dysfunction. Recent advancements in the characterisation of the molecular basis of the extranuclear signalling of sex steroids help to clarify the role of oestrogen and progesterone in the brain, and may turn out to be of relevance for clinical purposes. This review highlights the regulatory effects of oestrogens and progesterone on actin cytoskeleton and neurone morphology, as well as recent progresses in the characterisation of these mechanisms, providing insights and working hypotheses on possible clinical applications for the modulation of these pathways in the central nervous system.
Alterations in the antioxidant status of patients suffering from diabetes mellitus and associated cardiovascular complications

In view of the high prevalence of type 2 diabetes mellitus, this study aimed at determining the total plasma antioxidant capacity of type 2 diabetic patients with and without macrovascular complications. The erythrocyte catalase level was also evaluated because of the implication of catalase as a risk factor in diabetes. 90 age-­‐, gender-­‐ and body mass index-­‐matched subjects were used for this study and divided into healthy subjects (Group I, n=30), diabetic patients (Group II, n=30) and diabetic patients with cardiovascular complications (Group III, n=30). Blood samples collected from 90 eligible subjects were analyzed for glucose, HbA1c, urea, creatinine, total cholesterol, triglyceride, HDL and LDL cholesterol levels. Blood antioxidant activity and erythrocyte catalase levels were assessed. The mean antioxidant status values of Groups II and III were found to be significantly lower than that of Group I (p < 0.05). A significant decrease was also observed in the mean catalase level of Groups II and III as compared to Group I (p < 0.05) while a significant increase in fasting blood glucose level, glycated hemoglobin, triglycerides and urea was observed in Groups II and III compared to Group I. These data suggest that the in vivo antioxidant defense was highly compromised in patients with diabetes and associated cardiovascular complications although they were on medication, thereby suggesting the potential contributory beneficial effects of exogenous antioxidants. Furthermore, a reduction in catalase level may suggest the role of increasing hydrogen peroxide concentration in the disease progression. KEY WORDS: Antioxidant; Erythrocyte catalase; Cardiovascular complications; Type 2 diabetes mellitus
A Selective Ideational Apraxic Agraphia for Consonants

Aim: The proposed graphemic area in the dominant hemisphere contains letter representations that are responsible for guiding the skilled movements required for writing and for recognition of the physical features of letters. Dysfunction in this system may cause apraxic agraphia. In this study, writing performance of a right-handed, left hemisphere damaged, 12-year old apraxic agraphic patient with a native language of shallow ortography is analysed. Methods: Writing performance was evaluated with several different word lists, each holding same amount of letters, novel words (non-word), words, functors, and high-imagery and low-imagery words. Non-words were derived from words by changing a single letter. Results: A selective writing impairment limited to the left hand was observed. Her deficit was graphemic in nature; she made no phonological errors during spontaneous speech and oral naming. Writing was not affected by lexical factors (grammatical class, word length, or abstract quality) or lexicality (word, non-word, functor). In the entire corpus of responses, she wrote 2 of 154 vowel letters (1.3%) and 51 of 232 consonant letters (22.0%) incorrectly. Conclusions: It is proposed that the corpus callosum carries the interhemispheric control of praxis and writing at different levels, praxis for writing carried separately from praxis in general and within praxis for writing vowels and consonants are handled separately.
Sleep Medicine Pearls

Sleep medicine disorders are among the most frequent health complaints physicians encounter: one third of adults experience occasional or persistant sleep problems. These disorders become a major health problem when they impair daytime functioning. Working in the format of the popular Pearls Series(r) , noted sleep medicine authority Dr. Richard Berry presents 100 cases that review the key elements in the evaluation and management of patients with a wide variety of sleep disorders.
Distribution of cerebral blood flow in the dominant hemisphere during motor ideation and motor performance

Distribution of activity in the dominant (left) hemisphere was studied with a multidetector instrument during diagnostic measurements of regional cerebral blood flow in 6 patients, 4 of them neurologically normal. Computer‐calculated charts, in color, of the flow/activity distribution—“cerebral ideograms”—were obtained in three situations: at rest, during motor ideation (attempts to conceive of rhythmic clenching movements of the right hand), and during actual movements of the right hand. Motor ideation changed the normal “hyperfrontal” resting flow distribution, and an increase of the hemisphere mean flow was recorded. The increase was especially marked in frontal and temporal structures. This pattern differed from the one during actual hand movements, when a rolandic flow increase was seen. The result suggests that centers for motor ideation have a different cerebral location than those which control the actual hand movement.