Artificial intelligence on the identification of risk groups for osteoporosis, a general review.

INTRODUCTION: The goal of this paper is to present a critical review on the main systems that use artificial intelligence to identify groups at risk for osteoporosis or fractures. The systems considered for this study were those that fulfilled the following requirements: range of coverage in diagnosis, low cost and capability to identify more significant somatic factors. METHODS: A bibliographic research was done in the databases, PubMed, IEEExplorer Latin American and Caribbean Center on Health Sciences Information (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, Web of Science, and Science Direct searching the terms "Neural Network", "Osteoporosis Machine Learning" and "Osteoporosis Neural Network". Studies with titles not directly related to the research topic and older data that reported repeated strategies were excluded. The search was carried out with the descriptors in German, Spanish, French, Italian, Mandarin, Portuguese and English; but only studies written in English were found to meet the established criteria. Articles covering the period 2000-2017 were selected; however, articles prior to this period with great relevance were included in this study. DISCUSSION: Based on the collected research, it was identified that there are several methods in the use of artificial intelligence to help the screening of risk groups of osteoporosis or fractures. However, such systems were limited to a specific ethnic group, gender or age. For future research, new challenges are presented. CONCLUSIONS: It is necessary to develop research with the unification of different databases and grouping of the various attributes and clinical factors, in order to reach a greater comprehensiveness in the identification of risk groups of osteoporosis. For this purpose, the use of any predictive tool should be performed in different populations with greater participation of male patients and inclusion of a larger age range for the ones involved. The biggest challenge is to deal with all the data complexity generated by this unification, developing evidence-based standards for the evaluation of the most significant risk factors.

Next-generation sequencing of 100 candidate genes in young victims of suspected sudden cardiac death with structural abnormalities of the heart.

BACKGROUND: In sudden, unexpected, non-traumatic death in young individuals, structural abnormalities of the heart are frequently identified at autopsy. However, the findings may be unspecific and cause of death may remain unclear. A significant proportion of these cases are most likely caused by inherited cardiac diseases, and the cases are categorized as sudden cardiac death (SCD). The purpose of this study was to explore the added diagnostic value of genetic testing by next-generation sequencing (NGS) of a broad gene panel, as a supplement to the traditional forensic investigation in cases with non-diagnostic structural abnormalities of the heart. METHODS AND RESULTS: We screened 72 suspected SCD cases (<50 years) using the HaloPlex Target Enrichment System (Agilent) and NGS (Illumina MiSeq) for 100 genes previously associated with inherited cardiomyopathies and channelopathies. Fifty-two cases had non-diagnostic structural cardiac abnormalities and 20 cases, diagnosed with a cardiomyopathy post-mortem (ARVC = 14, HCM = 6), served as comparators. Fifteen (29%) of the deceased individuals with non-diagnostic findings had variants with likely functional effects based on conservation, computational prediction, allele-frequency and supportive literature. The corresponding frequency in deceased individuals with cardiomyopathies was 35% (p = 0.8). CONCLUSION: The broad genetic screening revealed variants with likely functional effects at similar high rates, i.e. in 29 and 35% of the suspected SCD cases with non-diagnostic and diagnostic cardiac abnormalities, respectively. Although the interpretation of broad NGS screening is challenging, it can support the forensic investigation and help the cardiologist's decision to offer counselling and clinical evaluation to relatives of young SCD victims.

[Clinical research outside of teaching hospitals: Current situation in north-eastern France]. / La recherche clinique hors des centres hospitaliers universitaires : état des lieux dans l'inter-région Est.

BACKGROUND: Most clinical research in France takes place in teaching hospitals. There are, however, many advantages to developing it in other hospitals: access to innovative treatments, improvement in healthcare quality, attractiveness of hospitals, increased trial inclusion rates and reduced selection bias. The objectives of our study were to report on the current situation of clinical research outside teaching hospitals. METHODS: A three-stage survey was conducted between January 2012 and May 2013 in non-teaching hospitals of north-eastern France. First, questionnaires were sent to administrative and medical boards of all hospitals with more than 100 beds, then to head doctors of every department in hospitals with more than 300 beds and finally meetings were organized with members of 20 selected hospitals. RESULTS: The administrative and medical boards of 85 hospitals participated in the first stage of the survey; half of these hospitals were engaged in clinical research activities and for 10 the internal structuring was cross-disciplinary. Answers from 178 departments were obtained during the second stage; 47% reported a clinical research activity. Meetings with research teams in 20 hospitals allowed us to identify difficulties concerning research funding, transversal organization and sponsoring. CONCLUSION: Clinical research existed in more than half of the respondent non-teaching hospitals. Obstacles to its development can be grouped in three categories: 1) internal structuring of clinical research, 2) access to information and knowledge of how clinical research functions and to interlocutors outside the hospital and 3) access to skills necessary to sponsor clinical research.

Next-generation sequencing of 34 genes in sudden unexplained death victims in forensics and in patients with channelopathic cardiac diseases.

Sudden cardiac death (SCD) is responsible for a large proportion of sudden deaths in young individuals. In forensic medicine, many cases remain unexplained after routine postmortem autopsy and conventional investigations. These cases are called sudden unexplained deaths (SUD). Genetic testing has been suggested useful in forensic medicine, although in general with a significantly lower success rate compared to the clinical setting. The purpose of the study was to estimate the frequency of pathogenic variants in the genes most frequently associated with SCD in SUD cases and compare the frequency to that in patients with inherited cardiac channelopathies. Fifteen forensic SUD cases and 29 patients with channelopathies were investigated. DNA from 34 of the genes most frequently associated with SCD were captured using NimbleGen SeqCap EZ library build and were sequenced with next-generation sequencing (NGS) on an Illumina MiSeq. Likely pathogenic variants were identified in three out of 15 (20%) forensic SUD cases compared to 12 out of 29 (41%) patients with channelopathies. The difference was not statistically significant (p = 0.1). Additionally, two larger deletions of entire exons were identified in two of the patients (7%). The frequency of likely pathogenic variants was >2-fold higher in the clinical setting as compared to SUD cases. However, the demonstration of likely pathogenic variants in three out of 15 forensic SUD cases indicates that NGS investigations will contribute to the clinical investigations. Hence, this has the potential to increase the diagnostic rate significantly in the forensic as well as in the clinical setting.

Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor 2.

The ability of dendritic cells (DC) to initiate immune responses in naive T cells is dependent upon a maturation process that allows the cells to develop their potent Ag-presenting capacity. Although immature DC can be derived in vitro by treatment of peripheral blood monocytes with GM-CSF and IL-4, additional signals such as those provided by TNF-alpha, CD40 ligand, or LPS are required for complete maturation and maximum APC function. Because we recently found that microbial lipoproteins can activate monocytes and DC through Toll-like receptor (TLR) 2, we also investigated whether lipoproteins can drive DC maturation. Immature DC were cultured with or without lipoproteins and were monitored for expression of cell surface markers indicative of maturation. Stimulation with lipopeptides increased expression of CD83, MHC class II, CD80, CD86, CD54, and CD58, and decreased CD32 expression and endocytic activity; these lipopeptide-matured DC also displayed enhanced T cell stimulatory capacity in MLR, as measured by T cell proliferation and IFN-gamma secretion. The lipid moiety of the lipopeptide was found to be essential for induction of maturation. Preincubation of maturing DC with an anti-TLR2 blocking Ab before addition of lipopeptide blocked the phenotypic and functional changes associated with DC maturation. These results demonstrate that lipopeptides can stimulate DC maturation via TLR2, providing a mechanism by which products of bacteria can participate in the initiation of an immune response.

["Population and xenograft" investigation. Preliminary results]. / Enqu¿ete "population et x¿enogreffe". R¿esultats pr¿eliminaires.

The chronic shortage of human organs is the argument for xenotransplantation. In emergencies, acceptability is closely linked to the benefit. Little information is available on attitudes towards xenotransplantation. A poll of the attitudes was carried out, based on a questionnaire with targeted questions and background information. The goal of the study was to have a better understanding of people's attitudes towards xenotransplantation and to know the eventual changes in the answers after having been given information. For 75% of the sample, xenotransplantation would be a future biotechnology. The animal sources that would be considered for xenotransplantation were the pig and monkey. A period of ten years or more is necessary for 69% of the respondents before xenografts are performed routinely; for 19%, five years or less are needed. Human organ donation should be continued, according to 90% of the sample. Roughly, 46.4% support xenotransplantation, though in the case of a life-or-death situation acceptance reaches 65.7%. This level is higher (77%) for relatives or unknown people (71%); 74% of respondents were in favour of using normal animals and a large majority (88%) support research on xenotransplantation. A good level of confidence in medical biotechnology research and practice is suggested by this study, contrary to the results of a European survey on biotechnology.

Anesthesia for pediatric external beam radiation therapy.

BACKGROUND: For very young patients, anesthesia is often required for radiotherapy. This results in multiple exposures to anesthetic agents over a short period of time. We report a consecutive series of children anesthetized for external beam radiation therapy (EBRT). METHODS: Five hundred twelve children < or = 16 years old received EBRT from January 1983 to February 1996. Patient demographics, diagnosis, anesthesia techniques, monitoring, airway management, complications, and outcome were recorded for the patients requiring anesthesia. RESULTS: One hundred twenty-three of the 512 children (24%) required 141 courses of EBRT with anesthesia. Anesthetized patients ranged in age from 20 days to 11 years (mean 2.6 +/- 1.8 ). The frequency of a child receiving EBRT and requiring anesthesia by age cohort was: < or = 1 year (96%), 1-2 years (93%), 2-3 years (80%), 3-4 years (51%), 4-5 years (36%), 5-6 years (13%), 6-7 years (11%), and 7-16 years (0.7%). Diagnoses included: primary CNS tumor (28%), retinoblastoma (27%), neuroblastoma (20%), acute leukemia (9%), rhabdomyosarcoma (6%), and Wilms' tumor (4%). Sixty-three percent of the patients had been exposed to chemotherapy prior to EBRT. The mean number of anesthesia sessions per patient was 22 +/- 16. Seventy-eight percent of the treatment courses were once daily and 22% were twice daily. Anesthesia techniques included: short-acting barbiturate induction + inhalation maintenance (21%), inhalation only (20%), ketamine (19%), propofol only (12%), propofol induction + inhalation maintenance (7%), ketamine induction + inhalation maintenance (6%), ketamine or short-acting barbiturate induction + inhalation maintenance (6%). Monitoring techniques included: EKG (95%), O2 saturation (93%), fraction of inspired O2 (57%), and end-tidal CO2 (55%). Sixty-four percent of patients had central venous access. Eleven of the 74 children with a central line developed sepsis (15%): 6 of the 11 were anesthetized with propofol (55%), 4 with a short-acting barbiturate induction plus inhalation maintenance (36%), and 1 with inhalation alone (9%). Eight of the 11 (73%) received prior chemotherapy. CONCLUSION: Anesthesia was generally necessary at < or = 3 years, and rarely required at > 5 years of age. Sepsis associated with frequent use of the central venous access line was seen in 15% of the patients with these lines.

IFN-gamma-dependent nitric oxide production is not linked to resistance in experimental African trypanosomiasis.

Resistance to African trypanosomes is dependent on B cell and Th1 cell responses to the variant surface glycoprotein (VSG). While B cell responses to VSG control levels of parasitemia, the cytokine responses of Th1 cells to VSG appear to be linked to the control of parasites in extravascular tissues. We have recently shown that IFN-gamma knockout (IFN-gamma KO) mice are highly susceptible to infection and have reduced levels of macrophage activation compared to the wild-type C57BL/6 (WT) parent strain, even though parasitemias were controlled by VSG-specific antibody responses in both strains. In the present work, we examine the role of IFN-gamma in the induction of nitric oxide (NO) production and host resistance and in the development of suppressor macrophage activity in mice infected with Trypanosoma brucei rhodesiense. In contrast to WT mice, susceptible IFN-gamma KO mice did not produce NO during infection and did not develop suppressor macrophage activity, suggesting that NO might be linked to resistance but that suppressor cell activity was not associated with resistance or susceptibility to trypanosome infection. To further examine the consequence of inducible NO production in infection, we monitored survival, parasitemia, and Th cell cytokine production in iNOS KO mice. While survival times and parasitemia of iNOS KO mice did not differ significantly from WT mice, VSG-specific Th1 cells from iNOS KO mice produced higher levels of IFN-gamma and IL-2 than cells from WT mice. Together, these results show for the first time that inducible NO production is not the central defect associated with susceptibility of IFN-gamma KO mice to African trypanosomes, that IFNgamma-induced factors other than iNOS may be important for resistance to the trypanosomes, and that suppressor macrophage activity is not linked to either the resistance or the susceptibility phenotypes.

Resistance to the African trypanosomes is IFN-gamma dependent.

The role of variant surface glycoprotein (VSG)-specific Th cell responses in determining resistance to the African trypanosomes was examined by comparing Th cell responses in relatively resistant and susceptible mice as well as in cytokine gene knockout mice infected with Trypanosoma brucei rhodesiense. Resistant B10.BR and C57BL/6 mice expressed Th1 cell cytokine responses to VSG stimulation during infection, while susceptible C3H mice produced weak or no Th1 cell cytokine responses. Neither resistant B10.BR and C57BL/6 mice nor susceptible C3H mice made detectable Th2 cell cytokine responses to parasite Ag. To more closely examine the potential role of IFN-gamma and other cytokines in host resistance, we determined the resistance phenotypes and Th cell responses of IFN-gamma and IL-4 knockout mice. Infected C57BL/6-IFN-gamma knockout mice were as susceptible as C57BL/6-scid mice and made an IL-2, but not an IL-4, cytokine response to VSG, while C57BL/6-IL-4 knockout mice were as resistant as the wild-type strain and exhibited both IL-2 and IFN-gamma cytokine responses. Passive transfer of spleen cells from wild-type mice to IFN-gamma knockout mice resulted in enhanced survival. Both wild-type and IFN-gamma knockout mice controlled parasitemia with VSG-specific Ab responses, although parasitemias were higher in the IFN-gamma knockout mice. Overall, this study demonstrates for the first time that relative resistance to African trypanosomes is associated with a strong Th1 cell response to parasite Ags, that IFN-gamma, but not IL-4, is linked to host resistance, and that susceptible animals do not make compensatory Th2 cell responses in the absence of Th1 cell cytokine responses.

Autoreceptor-mediated regulation of GABA release: role of uptake inhibition and effects of novel GABAB antagonists.

While the role of GABAB autoreceptors in the regulation of GABA release in synaptosomes and brain slices is well established, little is known about their role in vivo. Doubts have arisen because there is an apparent discrepancy between the frequencies at which GABA neurons fire and the frequency range within which autoreceptor regulation is observed in vitro. To see whether this apparent mismatch could be due to the use of a GABA uptake inhibitor in the release experiments in slices, we have compared the frequency dependencies of GABA release in the presence and absence of uptake inhibition. Before-hand, the previously incomplete frequency curve in the presence of uptake inhibition was extended at the lower end. To achieve this, stimulation was performed by means of groups of 4 pseudo-one-pulses (POP's) at inter-POP intervals corresponding to frequencies of 0.015625-0.5 Hz. It could be shown that activation of the GABAB autoreceptor by endogenously released GABA begins at a stimulation frequency as low as 0.0625 Hz. Experiments with the antagonist, CGP 35348, at inter-POP intervals of 1 min, at which the preceding POP has no longer an effect on GABA release during the next one, showed that basal release alone already substantially activated the autoreceptor. The frequency dependence in the absence as compared to the presence of uptake inhibition was shifted towards higher frequencies by a factor of 4. We do not consider this enough to remove our doubts about the in vivo operativity of GABAB autoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Determining health risks associated with disinfectants and disinfection by-products: research needs.

In order to minimize the levels of potentially toxic disinfectants and disinfection by-products in treated water while maintaining adequate protection against microbiological contamination, the total risks associated with disinfection have to be measured and compared with the risks from microbial agents. Because much work has already been carried out on chlorination and its by-products, it is recommended that research focus on major disinfection alternatives, i.e., ozonation, chloramination, carbon dioxidation, and the most practical combinations of these options. The primary research needs are (1) assessment of the relative toxicological hazards of the disinfectants and their by-products and (2) development of biologically based models for the dose-response relationships of these chemicals.

Selective aortic arch perfusion during cardiac arrest: a new resuscitation technique.

STUDY OBJECTIVES: To demonstrate the technique of selective aortic arch perfusion during cardiac arrest and to observe the hemodynamic effects of volume infusion and aortic epinephrine administration. DESIGN: Sequential series, nonrandomized, noncontrolled. TYPE OF PARTICIPANTS: Fourteen mongrel dogs weighing 21 to 36 kg. INTERVENTIONS: Animals had midaortic arch pressure, right atrial pressure, and descending aortic arch balloon occlusion catheters placed. After ten minutes of ventricular fibrillation, balloon inflation and aortic arch infusions were initiated as follows: group 1 (six), 30 mL/kg/min of 0.9% NaCl for two minutes; group 2 (four), 30 mL/kg/min of oxygenated lactated Ringer's with 2 mg/L epinephrine for two minutes, followed by CPR; and group 3 (four), 20 mL/kg/min of oxygenated perfluorochemicals with 4 mg/L epinephrine for one minute, then CPR. MEASUREMENTS AND MAIN RESULTS: Midaortic arch pressure, right atrial pressure, and coronary perfusion pressure each rose significantly in all groups. Midaortic arch pressure and coronary perfusion pressure increases were greater in groups 2 and 3 than in group 1. In groups 1 and 2, right atrial pressure increases at end-selective aortic arch perfusion were excessive as midaortic arch pressure and right atrial pressure increased linearly and similarly after 20 to 30 seconds. In groups 2 and 3, CPR-diastolic midaortic arch pressure and coronary perfusion pressure after selective aortic arch perfusion were good and similar to midaortic arch pressure and coronary perfusion pressure at end-selective aortic arch perfusion. CONCLUSION: Selective aortic arch perfusion is technically feasible, but excessive right atrial pressure increases limit maximal infusion rates and volumes. Selective aortic arch perfusion infusates with epinephrine produce greater midaortic arch pressure and coronary perfusion pressure during infusion than infusate without epinephrine. Controlled studies are needed to determine if selective aortic arch perfusion improves resuscitation outcome.

On the mechanism of kidney stone disintegration by acoustic shock waves.

In the present study we have, by theoretical and experimental investigations, especially concentrated on the importance of acoustic streaming, transient cavitation and microstreaming in the fluid close to the stone. Artificial stones, round stones 20 mm in diameter made of Plaster of Paris or rectangular flat stones, 25 x 25 x 15 mm, were suspended in a water bath at the focus of an EDAP LT01 lithotripter. "Unprotected" stones were disintegrated while stones surrounded by a layer of silicone showed no or very small disintegration. For successful destruction of the calculus, it seems to be essential that the stones are surrounded by a liquid, i.e., water.

Measurement of blood perfusion in tissue using Doppler ultrasound.

A diagnostic tool for noninvasive evaluation of microcirculatory blood flow using continuous-wave CW Doppler ultrasound is presented. In this study, the properties of this method are investigated both theoretically and experimentally. The method utilizes a nondirectional CW Doppler flowmeter. Blood perfusion in tissue is shown to be proportional to the integral integral of fS (f)df where S(f) is the Doppler power spectrum and f is the Doppler frequency. The instrumentation needed to implement the method is described. Using an experimental flow model it is demonstrated that the above integral is proportional to the product between the number of scatterers in the sample volume of the Doppler probe and the mean speed of these scatterers. This is true even for low flow velocities (down to 1 mm/s). The results from in-vivo measurements on tissues in the finger, and the calf demonstrate that the method can monitor changes in the blood perfusion. It also shows the present limitations of the method due to movement artefacts.

Comparison of quarter-hourly on-line dynamic headspace analysis to purge-and-trap analysis of varying volatile organic compounds in drinking water sources.

On-line dynamic headspace analysis was refined for the quarter-hourly monitoring of select volatile organic compounds (VOCs) in ground and surface waters, for extended periods of time. Hourly comparisons were made to on-line purge-and-trap analysis, and to purge-and-trap analysis after sample preservation and storage. Variations in VOC concentrations of 6047% biweekly, 222% daily, 97% hourly, and 35% quarter-hourly were observable, with the 15-min cycle of the dynamic headspace analysis. The headspace analyzer had superior retention time stability, required less maintenance, and had 1/4 the analysis time as a typical purge-and-trap-gas chromatograph system used for hourly comparisons.