Comparison of porcine thorax to gelatine blocks for wound ballistics studies.

Tissue simulants are typically used in ballistic testing as substitutes for biological tissues. Many simulants have been used, with gelatine amongst the most common. While two concentrations of gelatine (10 and 20 %) have been used extensively, no agreed standard exists for the preparation of either. Comparison of ballistic damage produced in both concentrations is lacking. The damage produced in gelatine is also questioned, with regards to what it would mean for specific areas of living tissue. The aim of the work discussed in this paper was to consider how damage caused by selected pistol and rifle ammunition varied in different simulants. Damage to gelatine blocks 10 and 20 % in concentration were tested with 9 mm Luger (9 × 19 full metal jacket; FMJ) rounds, while damage produced by .223 Remington (5.56 × 45 Federal Premium® Tactical® Bonded®) rounds to porcine thorax sections (skin, underlying tissue, ribs, lungs, ribs, underlying tissue, skin; backed by a block of 10 % gelatine) were compared to 10 and 20 % gelatine blocks. Results from the .223 Remington rifle round, which is one that typically expands on impact, revealed depths of penetration in the thorax arrangement were significantly different to 20 % gelatine, but not 10 % gelatine. The level of damage produced in the simulated thoraxes was smaller in scale to that witnessed in both gelatine concentrations, though greater debris was produced in the thoraxes.

Parental work schedules and child overweight and obesity.

OBJECTIVE: Studies in school-age children have consistently shown a positive association between maternal paid work hours and child obesity. However, there is conflicting evidence about the impact of maternal work hours scheduled at nonstandard times (for example, evenings, nights or weekends), and no previous examination of paternal work schedules and child weight. We examined the associations between maternal, paternal and combined parental paid work schedules and overweight/obesity in children at age 9 years. METHODS: Data were analysed from the most recent follow-up of 9-year-old children (n=434) in an Australian birth cohort study. Children were measured and classified as overweight/obese using the International Obesity Taskforce body mass index cutoff points. Current working conditions of parents were obtained from a structured interview with the primary caregiver. Logistic regression analyses were used to investigate the effect of parental work schedules on child overweight/obesity with adjustment for a range of sociodemographic and household factors associated with parental employment and child weight. RESULTS: At 9 years of age, 99 children (22.8%) were overweight or obese. When parental work schedules were examined separately, child overweight/obesity was significantly associated with paternal nonstandard work schedules (adjusted odds ratio (OR) 1.97, 95% confidence interval (CI) 1.08-3.61). There was no association with any type of maternal work schedule. We also found an association between child overweight/obesity and circumstances in which both parents worked nonstandard schedules; however, this was of borderline statistical significance in the adjusted models (adjusted OR 2.26, 95% CI 0.99-5.16). CONCLUSION: Work hours scheduled at nonstandard times, when worked by the father or both parents, were associated with child overweight and obesity. These findings indicate the potential importance of fathers' paid work arrangements for child overweight/obesity, which until recently has largely been ignored.

[One case of nosocomial A(H1N1)v2009 influenza in Réunion Island]. / Un cas de grippe A(H1N1)v2009 nosocomiale à la Réunion.

A 19-year-old patient admitted in an oncology unit for an autograft (Hodgkin disease), developed on day 20 a fatal acute respiratory failure and multiple organ failure due to an infection of the A(H1N1)v2009 virus, which was acquired in the hospital, despite partial preventive measures. At that time, the specific vaccine was not available in Réunion. We discuss the nosocomial origin of the infection. Following the epidemic wave, the vaccination rate of the general population and the hospital employees remains very low.

[Severe cases of A(H1N1)v2009 infection in Réunion Island in 2009 and 2010]. / Formes graves d'infection par le virus A(H1N1)v2009 à La Réunion en 2009 et en 2010.

In the Southern hemisphere, Réunion Island acts as a sentinel for infections preferentially occurring during the austral winter that are likely to reach the Northern hemisphere a few months later. We relate the main features concerning patients that were admitted during years 2009 and 2010 in our intensive care unit with an A(H1N1)v2009 infection, mainly for acute respiratory distress. Demographic, clinical, and biological data as well as given medications and outcome were prospectively collected among all PCR-confirmed influenza-infected patients. In 2009 and 2010, 25 patients met the criteria. Patients' median age was 40.4 (±17.4) years. Most of them (22/25) had comorbidities such as: chronic diseases, overweight, obesity, pregnancy, and Down syndrome. Maximum bed-occupation rate was 10 days per million inhabitants. Main diagnosis for ICU admission was virus-related pneumonia. Twenty-two out of 25 patients needed mechanical ventilation, some required rescue therapies such as extracorporeal membranous oxygenation (ECMO) or hi-frequency oscillation ventilation (HFOV), both only available in few French hospitals. Within the study period, 12 patients died (48%) mainly of multi-organ failure. Through 2009 and 2010 autumn and winter periods, for several weeks, the A(H1N1)v2009 virus infection resulted in a significant increase of workload in Réunion Island ICUs. In 2010, the failure of the mass immunization campaign, particularly among the at-risk groups, led to severe cases of A(H1N1)v2009 infections, particularly among patients with comorbidities. Our data may contribute toward better management of influenza virus pandemics in the future.

Oxidative stress pathways highlighted in tumor cell immortalization: association with breast cancer outcome.

An improved understanding of cell immortalization and its manifestation in clinical tumors could facilitate novel therapeutic approaches. However, only rare tumor cells, which maintain telomerase expression in vitro, immortalize spontaneously. By expression-profiling analyses of limited-life primary breast tumor cultures pre- and post-hTERT transduction, and spontaneously immortalized breast cancer cell lines, we identified a common signature characteristic of tumor cell immortalization. A predominant feature of this immortalization signature (ImmSig) was the significant overexpression of oxidoreductase genes. In contrast to epithelial cells derived from low histologic grade primary tumors, which required hTERT transduction for the acquisition of ImmSig, spontaneously immortalizing high-grade tumor cultures displayed similar molecular changes independent of exogenous hTERT. Silencing the hTERT gene reversed ImmSig expression, increased cellular reactive oxygen species levels, altered mitochondrial membrane potential and induced apoptotic and proliferation changes in immortalized cells. In clinical breast cancer samples, cell-proliferation-pathway genes were significantly associated with ImmSig. In these cases, ImmSig expression itself was inversely correlated with patient survival (P=0), and was particularly relevant to the outcome of estrogen receptor-positive tumors. Our data support the notion that ImmSig assists in surmounting normal barriers related to oxidative and replicative stress response. Targeting a subset of aggressive breast cancers by reversing ImmSig components could be a practical therapeutic strategy.

[Is it worth delivering Direct-Current Counter shock to critically ill patients with supra-ventricular tachyarrhythmia?] / Vaut-il la peine de délivrer un choc électrique aux patients de réanimation avec tachycardie supra-ventriculaire ?

Supra-ventricular tachyarrhythmia and its treatment have been poorly investigated in ICU patients. AIMS: To evaluate efficacy and safety of cardioversion for supra-ventricular tachyarrhythmia in the intensive care unit (ICU). PATIENTS AND METHODS: Prospective inclusion of all patients who presented supra-ventricular tachyarrhythmias lasting≥30seconds in a single medico-surgical ICU, except cardiac surgery. Anti-arrhythmic drugs and/or direct-current cardioversion were administered on a liberal basis. RESULTS: During the 15-month study period, 108/846 patients (12.8%) experienced supra-ventricular tachyarrhythmias. Anti-arrhythmic drugs were administered in 78 patients (72%); mostly amiodarone (92%), and/or magnesium (23%), resulting in an overall conversion rate of 68%. Direct-current cardioversion was used in 26 patients (24%), (24 patients received drug enhancement by anti-arrhythmic drugs) with an immediate 80.8%-success rate. CONCLUSION: Direct-current cardioversion was associated with sustained conversion to sinus rhythm in 80.8% of ICU patients with supra-ventricular tachyarrhythmias, although most of them had already received drug enhancement.

[Management of cardiogenic shock: Results from a survey in France and Belgium]. / Prise en charge d'un patient en état de choc cardiogénique : résultats de l'enquête de pratique franco-belge.

PURPOSE: Physician survey on cardiogenic shock management; recommendations for the management of patients with cardiogenic shock are based mostly on experts' opinion. METHODS: Overall 1585 emails were sent to "senior" intensive care physicians from France and Belgium from September 2014 to march 2015. Response rate was 10% (157 respondents). Agreement was assessed based on RAND/UCLA methodology. RESULTS: Continuous monitoring of cardiac output, vascular filling, noninvasive ventilation were deemed appropriate. The use of systematic diuretics and dopamine seemed inappropriate. There was a strong agreement to use dobutamine as inotropic drug in first intention. The use of noradrenaline and adrenaline was considered appropriate. There was a strong agreement to use mechanical circulatory support, in particular extracorporeal life support, in refractory cardiogenic shock. Only 25% of responders felt that there are criteria of refractory cardiogenic shock. Concerning the objectives of systolic, diastolic and mean blood pressure, 95% of the responses were in the range between 70 to 100, 30 to 50, and 55 to 65mmHg, respectively. The target of SvO2 was between 55% and 75%, and cardiac index between 1.5 and 3L/min/m2 for 95% of responders. There was a strong agreement to maintain hemoglobin between 7 and 9.9g/dL. CONCLUSION: Based on our physician survey, we found an agreement in vascular filling and early enteral nutrition. Dobutamine and noradrenaline should be the preferred drugs, but not dopamine. Mechanical circulatory support (preferably with extracorporeal support) should be restricted to refractory cardiogenic shock. Those responses differed slightly from experts' opinion, available in terms of recommendations.

Implantable gastric stimulation to achieve weight loss in patients with a low body mass index: early clinical trial results.

This report describes the authors' early outcomes with implantable gastric stimulation (IGS) used to achieve weight loss in patients with a low body mass index (BMI). After prescreening of potential candidates with a selection algorithm, 24 patients (21 women and 3 men) with a low BMI (30-34.9) underwent IGS implantation at two centers. The patients had a mean age of 43 years (range, 32-60 years), a mean BMI of 33 (range, 30-36), and a mean weight of 92 kg (range, 80-117 kg). At this writing, 6 months postoperatively, there have been no serious adverse events related to the device. The mean percentage of excess weight loss (EWL) was 5.9%, with three patients explanted because of noncompliance. The mean waist circumference decreased 5.8%, which was significant (p = 0.009). A subset of nine patients (37.5%) had an EWL exceeding 10% (mean, 20.1%). A subset of low BMI patients lost a clinically significant amount of weight with IGS within 6 months. Further study is required for better identification of potential candidates for this novel approach.

Relationship between prostaglandin biosynthesis and the effect of insulin on hormone-stimulated lipolysis in rat adipose tissue.

Lipolysis in rat fat pads was studied by determination of free fatty acid and glycerol production in various experimental conditions (in the absence or presence of glucose, adrenalin and insulin). These results were compared to the accumulation of endogenous prostaglandins E2 and F2alpha during lipolysis. In the absence of glucose the prostaglandin production followed the adrenalin-induced fluctuations in released free fatty acids both in the presence or absence of insulin. In the presence of glucose and insulin, a drop in prostaglandin accumulation was observed whereas free fatty acids production was strongly stimulated. These results suggest that either free fatty acid composition is modified, influencing the activity of prostaglandin synthetase, or that there exists a specific mechanism controlling prostaglandin synthesis.

The development of a quantitative flexibility test for body armour and comparison with wearer trials.

In this paper a mechanical flexibility test is developed which can be used to assess multi layer body armour systems. This is compared with a subjective manual test, and then with the results of wearer trials conducted using the recently approved ISO body armour standard ISO 14876-1 (2002). A series of trials was conducted on six different ballistic and/or stab resistant body armour types with a variety of protection levels and constructions. These were tested using the mechanical test system in which the armour was forced through a 200 mm hole by a 100 mm hemispherical plunger. The results of this test were then compared to a second set of trials in which flexibility of the same armour was assessed by manual handling and flexing of the armour. Finally an ergonomic wearer trial was conducted with four armours according to ISO 14876-1 (2002) each armour being assessed by four volunteers and the results compared to flexibility data collected in the first two trials. It was shown that the mechanical flexibility test produced results which were in good agreement with a purely subjective flexibility assessment. These results in turn showed reasonable but not exact correlation with the wearer trials. The ISO wearer trials addressed other factors such as overall comfort and fit of the systems and so the results were not purely a function of flexibility.

Demonstrating the effect of forensic firearm countermeasures: Bullet characteristics generated due to barrel modifications.

Forensic awareness and the declining availability of firearms have resulted in an increase in the use of modified and re-activated firearms in crime. Although some modifications are undertaken to simply acquire a functioning firearm, others are perpetrated as a direct forensic countermeasure to prevent the association between a firearm and a crime. This article describes the effects of these modifications on bullet striation patterns imparted from the barrel to a fired bullet. The key results indicated that the investigated modifications display assessable characteristics. The use of an oversized barrel imparted striations consistent with firing with the absence of typical rifling. Subsequent or consecutively fired bullets possessed striation variations, with the first showing the least evidence of striations. The application of a choke resulted in more obvious bullet elongation compared to a smoothbore barrel. The restriction caused merging of lands and groves of the imparted rifling and obscured their usual definition. Effects of breech adaption were also characterised by observing the buckling and enlargement of the cartridge case. This deformity of the cartridge case was most evident when the barrel pressure increased due to the presence of the choke. From this study it was evident that unique characteristic impressions associated with different modifications most commonly found in criminal investigations can be utilised by a forensic expert and impart significant intelligence to an investigation.

Developmental expression analysis of the 1731 retrotransposon reveals an enhancement of Gag-Pol frameshifting in males of Drosophila melanogaster.

Extensive analyses of Drosophila melanogaster retrotransposon transcriptions in cultured cells or during development have been reported, but little is known about their translation during the development of the fly. Analysis of the translational products of the 1731 Drosophila melanogaster retrotransposon in Kc Drosophila cultured cells has been reported, showing the existence of primary products (Gag and Pol) and of processed polypeptides of various sizes. Study of 1731 retrotransposon expression at both levels of transcription and translation during the development of Drosophila melanogaster, is presented. 1731 transcripts were detected by in situ hybridization and 1731 proteins were detected by immunostaining and immunoblotting in embryos and in adult gonads. 1731 transcripts and proteins were detected in the mesoderm and central nervous system during embryonic development, in nurse cells and follicle cells in adult ovaries and in primary spermatocytes in adult testes. Moreover, Western blot analysis of the 1731 proteins with anti-Gag or anti-Pol antibodies in gonads revealed that the 1731 mRNA could be translated differentially according to the expressing tissue: essentially, ovarian translation and/or processing of 1731 products is different from that operating in testes, where the Gag-Pol fusion polyprotein is the most prominent product. Our results indicate that expression of the 1731 mobile element is regulated not only at the transcriptional level but also at the translational level, and that this regulation is different in the two sexes.

Comparative effects of cholera and Bordetella pertussis toxins on cyclic AMP and GTP levels and on lipolysis in rat adipocytes incubated in vitro.

The respective effects of cholera and Bordetella pertussis toxins were studied in time and concentration dependent experiments, following glycerol and fatty acid release, GTP and cAMP levels. Cholera toxin, after a lag time of 30 min, stimulated linearly GTP and cAMP accumulation and lipolysis (maximal effect: 2-fold increase at 5 micrograms/ml). Pertussis toxin presented a biphasic effect both in time and concentration dependent studies. Up to a maximum reached after 2 h with 1.4 units LPF/ml the stimulation affected GTP (3 fold) and cAMP (7 fold) levels, glycerol and fatty acid release (15 fold). Beyond this, an inhibition occurred, yielding a decrease towards basal values of GTP and cAMP content whereas the glycerol and fatty acid release was stopped. These results, which are the first reporting the fluctuation of the GTP content of intact cells challenged with bacterial toxins, show a close relationship between GTP and cyclic AMP levels and lipolytic activity.

Translation and fates of the gag protein of 1731, a Drosophila melanogaster retrotransposon.

An entire copy of 1731, a Drosophila melanogaster retrotransposon, was tagged by fusing in frame its putative gag gene with the reporter LacZ sequence. The high transfection efficiency of Drosophila virilis cells added to the absence of 1731 in their genome allowed, by combining histochemical staining and immunological detections, the demonstration of the translation of the 1731 gag gene. The gag protein is gathered in virus-like particles. Its occurrence in nuclei is consistent with a nuclear localization signal. The expression of the sense construction was inhibited by cotransfections with its antisense homologue.

The Gag polypeptides of the Drosophila 1731 retrotransposon are associated to virus-like particles and to nuclei.

1731 is a Drosophila melanogaster retrotransposon whose nucleotide sequence shows a proviral architecture with two long terminal repeats (LTRs) framing two internal Open Reading Frames (ORFs). The pol ORF2 of this mobile genetic element was demonstrated to code for an active Reverse Transcriptase (RT) and the ORF1 is expected to code for the structural Gag proteins of the virus-like particles (VLP). Using specific anti-Gag antibodies, we have characterized the 1731 Gag polypeptides expressed either in vitro or in Kc Drosophila melanogaster cultured cells. Together with the 1731 RT, the largest, likely post-translationaly-modified Gag polypeptides are gathered into cytoplasmic virus-like particles. Moreover and consistent with the nuclear localization signal present in the Gag sequence, we observed that a short 1731 Gag polypeptide is associated to the cell nuclei.

Physical contact with lymphocytes is required for reactivation of dormant HIV-1 in colonic epithelial cells: involvement of the HIV-1 LTR.

HIV-1 transmission from mucosal epithelial cells to lymphocytes is a potential mechanism of HIV-1 contamination during sexual intercourse. The human colon epithelial cell line HT-29, that is infectable by various HIV-1 strains, is a useful model for studying the molecular mechanisms involved in this process. In the present study, we show that HT-29 cells, when exposed to either HIV-1(LAI) or HIV-1(NDK) at a low multiplicity of infection, became infected but did not produce infectious virions. Using two-compartment cell culture chambers separated by a porous membrane, we showed that PBL were able to rescue infectious HIV-1 from latently infected HT-29 cells following a physical interaction between the two cell populations. In contrast, HT-29 cells, infected with the same viruses at a high multiplicity of infection, were able to produce mature viral particles that were infectious to PBL in absence of cellular contacts. Transient expression assays using an indicator gene under the control of the HIV-1 long terminal repeat revealed that cell-to-cell contact induced an activation of the HIV-1 promoter. These observations provide a putative molecular mechanism for transmission of HIV-1 from mucosal epithelial cells to lymphocytes.

Activation of the HIV type 1 long terminal repeat by X-irradiation involves two main Re1/NF-kappa B DNA-binding complexes.

Transcription of human immunodeficiency virus type 1 (HIV-1) is regulated by multiple cis-acting regulatory elements located in the viral long terminal repeats (LTRs). HIV-1 LTR enhancer is activated by a variety of heterologous viral, chemical, and physical agents. Studies have demonstrated that irradiation by X-rays induces transcription under the control of the HIV-1 LTR and that ionizing radiations activate DNA binding of the nuclear transcription factor NF-kappa B. Using various constructs expressing a reporter gene under the control of complete or deleted LTRs of HIV-1, we evidenced that a sequence located in the U3 region was involved in X-ray activation of the HIV-1 LTR in the human colonic carcinoma cell line HT29. The cis-acting element conferring X-ray responsiveness is indistinguishable from HIV NF-kappa B tandem repeat binding sites (HIV-1, kappa B). The present work has examined the effects of X-irradiation on the NF-kappa B transcription factor. Furthermore, we characterized the subunit composition of the two major nuclear NF-kappa B complexes that bind HIV-1 kappa B after X-ray irradiation.

X irradiation-induced transcription from the HIV type 1 long terminal repeat.

It has been previously shown in vitro and in vivo that the human immunodeficiency virus type 1 can be dramatically enhanced by certain heterologous viral, chemical, and physical (ultraviolet irradiation) agents. A common denominator shared by these agents is their ability to cause stress responses in cells. To analyze if a similar effect could occur by X irradiations, we tested the in vitro effect of X rays on HIV LTR-directed gene expression. The results demonstrate that the HIV-1 LTR is activated by X irradiation in a dose- and time-dependent manner, in all cell types tested, including epitheloid, fibroblast, and lymphoid cell lines. This study raises the possibility that exposure of AIDS patients to ionizing radiation (e.g., during treatment of epidemic Kaposi's sarcoma) could play a role in the activation of HIV-1 in vivo.

Tetradecanoyl phorbol-13-acetate counteracts the responsiveness of cultured thyroid cells to thyrotropin.

We have studied the effects of TPA on the metabolism of porcine thyroid cells cultured for 1-4 days in the absence (control cells) and in the presence of 0.1 mU/ml TSH (TSH cells). The phospholipid turnover, evaluated after a 2 hr incorporation of 32P-phosphate into phospholipids, is markedly modified by the presence of TPA (1.5 microM, 2 hr) in the incubation medium of control and TSH treated cells. The total incorporation is 3-4 times higher than untreated cells, the labelling of phosphatidylinositol (PI) is slightly decreased or unchanged whereas that of phosphatidylcholine (PC) is strongly increased. The increased labelling of PI, promoted by an acute TSH treatment is counteracted by TPA. This TPA effect is not observed when prelabelled cells are challenged for 5 min with the drug. A similar effect is observed when 10 nM TPA is added in the culture medium for 20 hr. The addition of TPA does not affect significantly the protein iodine content in 3 or 4 days control cells incubated for 45 min or 2 hr with 125I-iodine, but dramatically decreases the very high iodination rate of TSH cells. We have tested the TPA effect on the cyclic AMP accumulation for the last 5 min of a 2 hr incubation. TPA inhibits by about 50-80% the stimulation evoked by TSH and only by 10% that evoked by forskolin (0.1 mM). These results suggest a possible link between the PC turnover and the adenylate cyclase responsiveness to TSH and the iodination rate.

Relationships between the GTP content and the TSH-stimulated adenylate cyclase activity of cultured thyroid cells.

The adenylate cyclase activity of a crude membrane fraction derived from cells cultured for 4 days in the presence of TSH (0.1 mU/ml), when acutely stimulated with 25 mU/ml, is 5-8 times higher than that derived from control cells. It has been suggested that changes in the intracellular content of GTP resulting from TSH chronic treatment were the cause of the modified responsiveness of the cyclase. To investigate this hypothesis, a method for GTP determination was developed. The steady-state concentration of GTP in 4-day TSH-treated cells is 2-3 times higher than in 4-day control cells. The increase in GTP content is concentration dependent between 5 and 500 microU/ml TSH in the culture medium. It presents a maximum on day 4 of culture, but remains elevated up to day 5. Nevertheless the GTP content is not the only factor controlling the cyclase activity, indeed the addition of 0.1 mM GTP to membranes from control cells does not increase the response up to the level reached by membranes from TSH-treated cells. Treatment of the cells with virazole, a drug inhibiting the biosynthesis of guanyl nucleotides, greatly decreases the GTP level, but is unable to suppress the positive effect of the TSH chronic treatment on adenylate cyclase activity. These results show that the increase in GTP level resulting from culture of the cells in the presence of minute amounts of TSH is not exclusively linked to adenylate cyclase responsiveness to TSH.