Miracle-dz/UniFAR-FTUs huggingface dataset:
Multidrug-Resistant Tuberculous Meningitis in Children in Durban, South Africa

Background: Tuberculous meningitis (TBM) is the most frequent manifestation of central nervous system tuberculosis (TB) and is more common in children than in adults. The diagnosis of TBM in children is difficult because signs and symptoms are vague. Information about drug resistant TB in children is scarce, and there is no published information on drug resistant TBM in children. Methods: This is a retrospective review of medical records of children with culture-confirmed multidrug-resistant tuberculous meningitis (MDR-TBM) at King George V Hospital in Durban, South Africa. Results: Between 1992 and 2003, there were 8 children with MDR-TBM; 6 were HIV infected and 2 were HIV negative. Only one child survived. The diagnosis was made posthumously in almost all the children. Discussion: The changes in the cerebrospinal fluid (CSF) in early TBM can be nonspecific and can change rapidly; therefore, CSF studies should always include culture and susceptibility testing. Factors that contributed to the high mortality were disseminated TB, HIV infection, delay in diagnosis and treatment, the absence of a standardized approach to the management of MDR-TBM and the poor CSF penetration of most MDR-TB drugs. MDR-TB therapy should be considered if there is a history of TB: a MDR-TB contact or a poor clinical response to TB therapy despite adequate adherence to treatment. Early diagnosis is important because TBM in children is often associated with a grave outcome.
Cracking the neural code, treating paralysis and the future of bioelectronic medicine

The human nervous system is a vast network carrying not only sensory and movement information, but also information to and from our organs, intimately linking it to our overall health. Scientists and engineers have been working for decades to tap into this network and ‘crack the neural code’ by decoding neural signals and learning how to ‘speak’ the language of the nervous system. Progress has been made in developing neural decoding methods to decipher brain activity and bioelectronic technologies to treat rheumatoid arthritis, paralysis, epilepsy and for diagnosing brain‐related diseases such as Parkinson's and Alzheimer's disease. In a recent first‐in‐human study involving paralysis, a paralysed male study participant regained movement in his hand, years after his injury, through the use of a bioelectronic neural bypass. This work combined neural decoding and neurostimulation methods to translate and re‐route signals around damaged neural pathways within the central nervous system. By extending these methods to decipher neural messages in the peripheral nervous system, status information from our bodily functions and specific organs could be gained. This, one day, could allow real‐time diagnostics to be performed to give us a deeper insight into a patient's condition, or potentially even predict disease or allow early diagnosis. The future of bioelectronic medicine is extremely bright and is wide open as new diagnostic and treatment options are developed for patients around the world.
Diet quality in early pregnancy and its effects on fetal growth outcomes: the Infancia y Medio Ambiente (Childhood and Environment) Mother and Child Cohort Study in Spain.

BACKGROUND Maternal diet has been associated with fetal growth outcomes; however, evidence is scarce on the role of dietary quality. OBJECTIVE The objective was to assess the effect of diet quality during the first trimester of pregnancy, as measured by the Alternate Healthy Eating Index (AHEI) adapted for pregnancy, on fetal growth. DESIGN We studied 787 women and their newborns from a Spanish cohort study. Diet quality was assessed by using a modification of the AHEI. Adjusted birth weight, birth length, and head circumference were used as continuous outcomes. We used a customized model to define fetal growth restriction in weight, length, and head circumference. RESULTS After adjustment of multivariate models, a positive association was observed between diet quality and adjusted birth weight and adjusted birth length. The greatest differences were found between the fourth and first quintiles of the AHEI. Newborns of women in the fourth quintile were on average 126.3 g (95% CI: 38.5, 213.9 g) heavier and 0.47 cm (95% CI: 0.08, 0.86 cm) longer than those in the lowest quintile (P for trend = 0.009 and 0.013, respectively). Women with the highest AHEI scores had a significantly lower risk of delivering a fetal growth-restricted infant for weight (odds ratio: 0.24; 95% CI: 0.10, 0.55; P for trend = 0.001) than did women in the lowest quintile, but this was not the case for fetal growth restriction in length (P for trend = 0.538) or head circumference (P for trend = 0.070). CONCLUSION A high-quality diet in the first trimester of pregnancy is associated with birth size and the risk of fetal growth restriction.
Acquisition of Contextual Discrimination Involves the Appearance of a RAS-GRF1/p38 Mitogen-activated Protein (MAP) Kinase-mediated Signaling Pathway That Promotes Long Term Potentiation (LTP)*

Background: The ability to distinguish similar experiences is a critical aspect of memory. Results: Contextual discrimination involves LTP promoted by calcium-permeable AMPA-type glutamate receptors, RAS-GRF1 and p38 MAP kinase. Conclusion: A newly discovered, LTP-supporting, signaling pathway contributes to a key component of memory formation. Significance: Defects in this signaling pathway may contribute to cognitive loss associated with neurological disorders. RAS-GRF1 is a guanine nucleotide exchange factor with the ability to activate RAS and RAC GTPases in response to elevated calcium levels. We previously showed that beginning at 1 month of age, RAS-GRF1 mediates NMDA-type glutamate receptor (NMDAR)-induction of long term depression in the CA1 region of the hippocampus of mice. Here we show that beginning at 2 months of age, when mice first acquire the ability to discriminate between closely related contexts, RAS-GRF1 begins to contribute to the induction of long term potentiation (LTP) in the CA1 hippocampus by mediating the action of calcium-permeable, AMPA-type glutamate receptors (CP-AMPARs). Surprisingly, LTP induction by CP-AMPARs through RAS-GRF1 occurs via activation of p38 MAP kinase rather than ERK MAP kinase, which has more frequently been linked to LTP. Moreover, contextual discrimination is blocked by knockdown of Ras-Grf1 expression specifically in the CA1 hippocampus, infusion of a p38 MAP kinase inhibitor into the CA1 hippocampus, or the injection of an inhibitor of CP-AMPARs. These findings implicate the CA1 hippocampus in the developmentally dependent capacity to distinguish closely related contexts through the appearance of a novel LTP-supporting signaling pathway.
Jitter transformations in measurement instruments and discrepancies between measurement results

Jitter measurement with different time domain instruments (TDI) have been extensively studied in numerous works. These works covered different measurement instruments including equivalent-time (ETO) or sampling and real-time oscilloscopes (RTO), time interval analyzers (TIA), etc. However, in the published papers there is a lack of analysis of jitter transformations in different TDIs. Some publications pointed out discrepancies between measurements results carried out by different instruments, but the reasons of the discrepancies have not been explained. In this paper we research jitter transformations for typical jitter terms measurements with different instruments. It is demonstrated that jitter transformation depends both - on the measured jitter term, and the type of measurement instrument used. It is shown that jitter undergoes different transformations in different instruments. These transformation models are studied. The distinctions of both deterministic and random jitter (DJ and RJ respectively) transformations of measurements using various instruments are illustrated and analyzed. The experiments are discussed. The obtained results help to explain the discrepancies between different TDI measurement results and establish correct jitter measurement methodology
Geographical difference of disease association in Streptococcus bovis bacteraemia.

From 1996 to 2001, 48 Streptococcus bovis strains were isolated from blood cultures of 37 patients in one hospital. Median patient age was 68 years (range: 1 day-88 years). The male : female ratio was 23 : 14. Most patients (97 %) had underlying diseases, including biliary tract disease in 14 (38 %), diabetes mellitus in 12 (32 %), liver parenchymal disease in seven (19 %), carcinoma of the colon in four (11 %) and other malignancies in four (11 %). No infective foci (indicative of primary bacteraemia) were identified in 15 patients (40 %) and 14 (38 %) had acute cholangitis/cholecystitis, but only four (11 %) had infective endocarditis. Two (5 %), three (8 %) and 32 (87 %) patients had S. bovis of biotypes I, II/1 and II/2, respectively, and three (8 %), two (5 %) and 32 (87 %) patients had S. bovis of genotypes 1, 2a and 2b, respectively. All isolates were sensitive to penicillin, cephalothin and vancomycin, 24 (65 %) were resistant to erythromycin and 15 (41 %) were resistant to clindamycin (these strains were also resistant to erythromycin). Thirteen isolates that were erythromycin- and clindamycin-resistant possessed the ermB gene, 10 possessed the ermT gene and one possessed both the ermB and ermT genes. Overall, seven patients (19 %) died. In contrast to most other reports from western countries, where carcinoma of the colon and infective endocarditis were the major underlying disease and infective focus associated with S. bovis bacteraemia, biliary tract disease and acute cholangitis and/or cholecystitis were the major underlying diseases associated with S. bovis bacteraemia in our locality.
Role of oxygen radicals in 12-O-tetradecanoylphorbol-13-acetate-induced squamous differentiation of cultured normal human bronchial epithelial cells.

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibits growth and induces terminal squamous differentiation of normal human bronchial cells when added to the culture media [J. C. Willey, A. J. Saladino, C. Ozanne, J. F. Lechner, and C. C. Harris, Carcinogenesis (lond.), 5: 209-215, 1984]. We have investigated the possibility of oxygen free radicals being involved as intermediates in this process. Electron paramagnetic resonance measurements using the spin-trapping agent 5,5-dimethyl-1-pyrroline-1-oxide failed to detect oxygen free radicals in bronchial epithelial cells exposed to TPA, although oxy radicals were detected in bronchial epithelial cells after a nontoxic exposure to menadione, and in human neutrophils after exposure to TPA. Addition to the culture media of free radical scavenger, i.e., reduced glutathione, N-acetylcysteine, D-alpha-tocopherol, copper (II) (3,5-diisopropylsalicyclic acid)2, or the combination of superoxide dismutase and catalase did not affect the dose-dependent growth inhibition of TPA on the bronchial epithelial cells. Moreover, exposure of the bronchial epithelial cells to TPA did not result in increased DNA single strand breaks measured by alkaline elution, as would be expected with a free radical mediated mechanism. Thus, our results argue against the importance of oxygen free radicals in the inhibition of growth and the induction of squamous differentiation by TPA in normal human bronchial epithelial cells.
Treatment of chemically induced oral ulcer using adipose‐derived mesenchymal stem cell sheet

BACKGROUND This study investigated the effects of mesenchymal stem cell (MSC) sheet transplantation on healing of chemically induced oral ulceration in a rabbit animal model. METHODS Oral mucosal ulcers were induced by topical application of filter paper soaked with 70% acetic acid to the anterior gingiva and buccal mucosa of 12 New Zealand white rabbits. The animals were randomly assigned to two groups: with (treatment group, n = 6) or without (control group, n = 6) cell sheets applied to ulcers. Gross findings were sequentially evaluated, and histologic examination was performed on day 7. RESULTS Based on gross inspection, ulceration resolved before day 5 in the treatment group; however, in the control group, healing was incomplete on day 7. In the treatment group, the total area of the ulcer decreased significantly from day 2 to day 5 (P < 0.001) and from day 5 to day 7 (P = 0.020), whereas the area decreased significantly from day 5 to day 7 in the control group (P < 0.001). Histologic and immunofluorescence examination revealed full-thickness mucosa healing and complete basal cell coverage in the treatment group; in contrast, only partial healing was observed on day 7 in the control group. CONCLUSIONS Cell sheet technology using MSC can be an alternative treatment for oral ulcerations in that it can decrease healing time without invasive properties.
Embryo implantation and GnRH antagonists: GnRH antagonists do not activate the GnRH receptor.

Recent suggestions that gonadotrophin-releasing hormone (GnRH) antagonists activate the GnRH receptor are discussed. Most of the studies cited in support of this suggestion are in-vitro studies, testing supra-pharmacological doses of GnRH analogues in cancer cell lines, whereas GnRH antagonists, e.g. ganirelix or cetrorelix, do not affect the steroidogenesis of human granulosa cells in vitro. In patients treated with GnRH antagonists prior to IVF or intracytoplasmic sperm injection (ICSI), oocyte maturity and fertilization rates are equal to those achieved following a long protocol of GnRH agonists. Although there is a tendency towards a lower pregnancy rate (not statistically significant) in the initial trials using GnRH antagonist with either recombinant FSH or human menopausal gonadotrophin (HMG) for ovarian stimulation, this new treatment option of GnRH antagonists facilitates short and simple treatment and improves the convenience and safety for the patient. As with GnRH agonists in the past, the clinical outcome of GnRH antagonist treatment will improve with time as more clinical experience is gained (learning curve) and the treatment protocol is optimized. Moreover, a GnRH agonist instead of human chorionic gonadotrophin (HCG) may be used for triggering ovulation and will decrease the cancellation rate and minimize the risk for developing ovarian hyperstimulation syndrome (OHSS).
Fes Tyrosine Kinase Promotes Survival and Terminal Granulocyte Differentiation of Factor-dependent Myeloid Progenitors (32D) and Activates Lineage-specific Transcription Factors*

The c-fps/fesproto-oncogene encodes a 92-kDa protein-tyrosine kinase that is involved in myeloid cell development and function. We have recently shown that expression of an activated allele of Fes (Fesact) in monocyte precursors resulted in their differentiation into functional macrophages through the activation of lineage-specific transcription factors. We now report that this kinase also plays a role in the survival and terminal differentiation of granulocyte progenitors. The expression of Fesact in factor-dependent 32D cells prevented their apoptotic death after interleukin-3 removal, but Fesact-expressing cells remained factor-dependent for proliferation. Removal of interleukin-3 from the Fesact-expressing cells was followed by granulocytic differentiation in the absence of granulocyte colony-stimulating factor within 4–8 days. The differentiated cells had distinctive granulocyte morphology and there was up-regulation of CD11b, Gr-1, and late differentiation markers such as lactoferrin, suggesting that this kinase induced terminal granulocytic differentiation. Concomitantly, Fesact down-regulated the macrophage marker F4/80, suggesting that the biological activity of Fes was coordinated in a lineage-specific manner. Further analysis showed that Fesact caused activation of CCAAT/enhancer-binding protein-α and STAT3, two transcription factors that are involved in granulocyte differentiation. Our results provide evidence that Fes may be a key component of the granulocyte differentiation machinery, and suggest a potential mechanism by which this kinase may regulate granulocyte-specific gene expression.
Increased thermal stability of proteins in the presence of naturally occurring osmolytes.

Organisms and cellular systems which have adapted to stresses such as high temperature, desiccation, and urea-concentrating environments have responded by concentrating particular organic solutes known as osmolytes. These osmolytes are believed to confer protection to enzyme and other macromolecular systems against such denaturing stresses. Differential scanning calorimetric (DSC) experiments were performed on ribonuclease A and hen egg white lysozyme in the presence of varying concentrations of the osmolytes glycine, sarcosine, N,N-dimethylglycine, and betaine. Solutions containing up to several molar concentrations of these solutes were found to result in considerable increases in the thermal unfolding transition temperature (Tm) for these proteins. DSC scans of ribonuclease A in the presence of up to 8.2 M sarcosine resulted in reversible two-state unfolding transitions with Tm increases of up to 22 degrees C and unfolding enthalpy changes which were independent of Tm. On the basis of the thermodynamic parameters observed, 8.2 M sarcosine results in a stabilization free energy increase of 7.2 kcal/mol for ribonuclease A at 65 degrees C. This translates into more than a 45,000-fold increase in stability of the native form of ribonuclease A over that in the absence of sarcosine at this temperature. Catalytic activity measurements in the presence of 4 M sarcosine give kcat and Km values that are largely unchanged from those in the absence of sarcosine. DSC of lysozyme unfolding in the presence of these osmolytes also results in Tm increases of up to 23 degrees C; however, significant irreversibly occurs with this protein. (ABSTRACT TRUNCATED AT 250 WORDS)
Tissue-based biomarkers in prostate cancer

ABSTRACT Introduction: Prostate cancer is a heterogeneous disease. Existing risk stratification tools based on standard clinlicopathologic variables (prostate specific antigen [PSA], Gleason score, and tumor stage) provide a modest degree of predictive ability. Advances in high-throughput sequencing has led to the development of several novel tissue-based biomarkers that can improve prognostication in prostate cancer management. Areas covered: The authors review commercially-available, tissue-based biomarker assays that improve upon existing risk-stratification tools in several areas of prostate cancer management, including the appropriateness of active surveillance and aiding in decision making regarding the use of adjuvant therapy. Additionally, some of the obstacles to the widespread adoption of these biomarkers and discuss several investigational sources of new biomarkers are discussed. Expert commentary: Work is ongoing to answer pertinent clinical questions in prostate cancer management including which patients should undergo biopsy, active surveillance, receive adjuvant therapy, and what systemic therapy is best in the first-line. Incorporation into novel biomarkers may allow for the incorporation of a ‘personalized’ approach to management. Further validation will be required and questions of cost must be considered before wide scale adoption of these biomarkers. Tumor heterogeneity may impose a ceiling on the prognostic ability of biomarkers using currently available techniques.
Wall shear stress rather than shear rate regulates cytoplasmic Ca++ responses to flow in vascular endothelial cells.

Recent evidence suggests that the vascular endothelial cell (EC) can sense the flow-rate over its surface and according to the information, regulates not only its own morphology and functions but also those of the surrounding smooth muscle and other tissues. There is now a discussion over which of the following mechanisms actually initiates the signal-transacting response of EC against flow: the mechanical shear deformation of the cell due to flow-oriented wall shear stress (tau), or the diffusional accumulation of vasoactive agonists on the cell surface modulated by wall shear rate (gamma) or both. To identify the relative importance of each mechanism, we examined quantitative changes in the cytoplasmic free Ca++ concentration ([Ca++]i) in cultured EC in the presence of the Ca++ mobilizing agonist ATP, i.e., a second messenger response of the internal signalling system, following the perfusion of two buffers with different viscosities (mu), which relates these factors as tau = mu gamma. The results of in vitro fluorescence photometry in EC with Fura-2 showed that the [Ca++]i level was enhanced with increase in the shear rate but to a greater extent with higher viscosity, and that the [Ca++]i levels at the same calculated level of shear stress were virtually identical, regardless of difference in shear rate and viscosity. This quantitative one-to-one relationship between the shear stress and the second messenger response suggests that wall shear stress rather than wall shear rate is the principal physical factor eliciting EC responses to flow.
Identification of New Genes Positively Regulated by Tri10 and a Regulatory Network for Trichothecene Mycotoxin Production

ABSTRACT Tri10, a regulatory gene in trichothecene mycotoxin-producing Fusarium species, is required for trichothecene biosynthesis and the coordinated expression of four trichothecene pathway-specific genes (Tri4, Tri5, Tri6, and Tri101) and the isoprenoid biosynthetic gene for farnesyl pyrophosphate synthetase (FPPS). We showed that six more trichothecene genes (Tri3, Tri7, Tri8, Tri9, Tri11, and Tri12) are regulated by Tri10. We also constructed a cDNA library from a strain of Fusarium sporotrichioides that overexpresses Tri10 (↑Tri10) and used cDNA derived from the ↑Tri10 strain and a non-Tri10-expressing strain (ΔTri10) to differentially screen macroarrays prepared from the cDNA library. This screen identified 15 additional Tri10-regulated transcripts. Four of these transcripts represent Tri1, Tri13, and Tri14 and a gene designated Tri15. Three other sequences are putative orthologs of genes for isoprenoid biosynthesis, the primary metabolic pathway preceding trichothecene biosynthesis. The remaining eight sequences have been designated Ibt (influenced by Tri10) genes. Of the 26 transcripts now known to be positively regulated by Tri10, 22 are positively coregulated by Tri6, a gene that encodes a previously characterized trichothecene pathway-specific transcription factor. These 22 Tri10- and Tri6-coregulated sequences include all of the known Tri genes (except for Tri10), the FPPS gene, and the other three putative isoprenoid biosynthetic genes. Tri6 also regulates a transcript that is not regulated by Tri10. Thus, Tri10 and Tri6 regulate overlapping sets of genes that include a common group of multiple genes for both primary and secondary metabolism.
FECHTEN: Sportverletzungen und Schäden beim Fechten unter besonderer Berücksichtigung des Kindes- und Jugendalters

Zusammenfassung Zusammenfassung Ziel dieser Studie sind die Darstellung der haufigsten akuten Sportverletzungen und Uberlastungsschaden bei jugendlichen Fechtern (16 Jahre) und der Vergleich mit der Altersgruppe der uber 16-Jahrigen. Die prospektive Studie basiert auf Daten uber einen Beobachtungszeitraum von funf Jahren und berucksichtigt dabei 293 Fechter, die am Olympiastutzpunkt Fechten Tauberbischofsheim trainieren. Es werden Ursachen der Verletzungen und Uberlastungsschaden aufgezeigt und entsprechende Trainingsempfehlungen gegeben.