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BACKGROUND: Acetaminophen is the most widely used analgesic today. A recent systematic review found increased adverse events and mortality at therapeutic dosage. Our aim was to challenge these results in a large sample of older adults living in nursing homes (NHs). DESIGN: Prospective study using data from the Impact of Educational and Professional Supportive Interventions on Nursing Home Quality Indicators project (IQUARE), a multicenter, individually tailored, nonrandomized controlled trial in NHs across southwestern France. SETTING/PARTICIPANTS: We studied data from 5429 participants living in 175 NHs (average age, 86.1 ± 8.1 years; 73.9% women). MEASUREMENTS: All prescriptions obtained at baseline were analyzed by a pharmacist for acetaminophen use as stand‐alone or associated. Myocardial infarction (MI) and strokes were reported from participants' medical records at 18‐month follow‐up. Dates of death were obtained. Data collection was done through an online questionnaire at baseline and at 18 months by NH staff. Analyses were realized in our total population and a population matched on propensity score of acetaminophen intake. Six models were run for each outcome. RESULTS: A total of 2239 participants were taking, on average, 2352 ± 993 mg of acetaminophen daily. Results for mortality were: hazard ratio (HR) = 0.97 (95% confidence interval [CI] = 0.86‐1.10). No associations between acetaminophen intake and the risk of mortality or MI were found. In one of our models, acetaminophen intake was associated with a significant increased risk of stroke in diabetic subjects (OR = 3.19; 95% CI = 1.25‐8.18; P = .0157). [Correction added March 16, 2019, after first publication online. In the previous sentence, "HR" was mistakenly used instead of "OR".] CONCLUSION: Despite old age, polypharmacy, and polymorbidity, acetaminophen was found safe for most, but not all, of our NH study population. Pain management in NHs is a health priority, and acetaminophen remains a good therapeutic choice as a first‐line analgesic. More studies are needed on older diabetic patients. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Post‐pneumonectomy empyema (PPE) is the most severe complication of pneumonectomy. Microbiology and its impact on management and prognosis have rarely been reported Methods: We retrospectively reviewed the files of a series of 37 consecutive patients with PPE over a 10‐year period with a special focus on microbiology, means used to treat empyema and prognosis. Results: PPE occurred within 14 days of pneumonectomy in 17 cases (early PPE) and after postoperative day 16 in 20 patients (delayed PPE). PPE was monomicrobial in 57% of cases. The most frequent pathogens were Staphylococcus sp. and Streptococcus sp. Polymicrobial empyema was more frequent in patients with early PPE than delayed PPE (65% vs 25%; P = .02). Video‐assisted thoracoscopic approach for cavity lavage was performed in 22 patients without broncho‐pleural fistulae (BPF), associated with antimicrobial therapy and drainage, and was successful in 13 cases (59%). Seventeen patients (46%) underwent an open window thoracostomy. Overall 90‐day post empyema mortality was 19%, with 6 deaths because of empyema in the early PPE group (35%), versus one (5%) in the delayed PPE group (P = .02). Conclusion: We distinguished 2 different PPE presentations: an early occurrence, mostly with polymicrobial cultures, including Gram‐negative bacteria, and associated with a high mortality rate. By contrast, delayed PPEs were mostly monomicrobial with Gram‐positive bacteria and associated with a better prognosis. VATS approach was successful in the majority of cases without BPF, even if some patients required secondary thoracostomy. PPE was associated with an excess of mortality especially when occurring in the early course after pneumonectomy. [ABSTRACT FROM AUTHOR]

This letter comments on the letter by Lai and Lin [ABSTRACT FROM AUTHOR]

Nefopam is a non-opioid, non-steroidal, centrally acting analgesic drug used to prevent postoperative pain, primarily in the context of multimodal analgesia. This paper reviews preclinical and clinical studies in which nefopam has been combined with opioids, non-steroidal anti-inflammatory compounds, and paracetamol. This report focuses on the literature during the last decade and discusses the translational efforts between animal and clinical studies in the context of multimodal or balanced analgesia. In preclinical rodent models of acute and inflammatory pain, nefopam combinations including opioids revealed a synergistic interaction or enhanced morphine analgesia in six out of seven studies. Nefopam combinations including non-steroidal anti-inflammatory drugs (NSAIDs) (aspirin, ketoprofen or nimesulide) or paracetamol likewise showed enhanced analgesic effects for the associated compound in all instances. Clinical studies have been performed in various types of surgeries involving different pain intensities. Nefopam combinations including opioids resulted in a reduction in morphine consumption in 8 out of 10 studies of severe or moderate pain. Nefopam combinations including NSAIDs (ketoprofen or tenoxicam) or paracetamol also demonstrated a synergic interaction or an enhancement of the analgesic effect of the associated compound. In conclusion, this review of nefopam combinations including various analgesic drugs (opioids, NSAIDs and paracetamol) reveals that enhanced analgesia was demonstrated in most preclinical and clinical studies, suggesting a role for nefopam in multimodal analgesia based on its distinct characteristics as an analgesic. Further clinical studies are needed to evaluate the analgesic effects of nefopam combinations including NSAIDs or paracetamol. [ABSTRACT FROM AUTHOR]

The relative importance of multiple vectors to the initial establishment, spread and population dynamics of invasive species remains poorly understood. This study used molecular methods to clarify the roles of commercial shipping and recreational boating in the invasion by the cosmopolitan tunicate, Botryllus schlosseri. We evaluated (i) single vs. multiple introduction scenarios, (ii) the relative importance of shipping and boating to primary introductions, (iii) the interaction between these vectors for spread (i.e. the presence of a shipping-boating network) and (iv) the role of boating in determining population similarity. Tunicates were sampled from 26 populations along the Nova Scotia, Canada, coast that were exposed to either shipping (i.e. ports) or boating (i.e. marinas) activities. A total of 874 individuals ( c. 30 per population) from five ports and 21 marinas was collected and analysed using both mitochondrial cytochrome c oxidase subunit I gene (COI) and 10 nuclear microsatellite markers. The geographical location of multiple hotspot populations indicates that multiple invasions have occurred in Nova Scotia. A loss of genetic diversity from port to marina populations suggests a stronger influence of ships than recreational boats on primary coastal introductions. Population genetic similarity analysis reveals a dependence of marina populations on those that had been previously established in ports. Empirical data on marina connectivity because of boating better explains patterns in population similarities than does natural spread. We conclude that frequent primary introductions arise by ships and that secondary spread occurs gradually thereafter around individual ports, facilitated by recreational boating. [ABSTRACT FROM AUTHOR]

1. The aim of the present study was to explore the concept of multimodal anaesthesia using a combination of two non-opioid analgesics, namely nefopam, a centrally acting non-opioid that inhibits monoamine reuptake, and paracetamol, an inhibitor of central cyclo-oxygenases. The antinociceptive characteristics of the combination were evaluated using four different animal models of pain. 2. In the mouse writhing test, antinociceptive properties were observed with ED values of 1.5 ± 0.2 and 120.9 ± 14.8 mg/kg for nefopam and paracetamol, respectively. In the mouse formalin test, both compounds significantly inhibited the licking time of the injected hind paw, with ED values in the early phase of 4.5 ± 1.1 and 330.7 ± 80.3 mg/kg for nefopam and paracetamol, respectively, compared with 4.3 ± 0.2 and 206.1 ± 45.1 mg/kg for nefopam and paracetamol, respectively, in the inflammatory phase. Isobolographic analysis revealed that this drug combination was synergistic in the writhing test and additive in the formalin test. 3. In a rat incision model of postoperative thermal hyperalgesia, coadministration of nefopam at a non-analgesic dose (3 mg/kg) with paracetamol at a low analgesic dose (300 mg/kg) showed the appearance of a strong antihyperalgesic effect, maintained for at least 3 h. In rat carrageenan-induced tactile allodynia, the combination of low analgesic doses of nefopam (10 or 30 mg/kg) with a non-analgesic dose of paracetamol (30 mg/kg), significantly blocked allodynia with a longer duration of efficacy. 4. In conclusion, coadministration of nefopam with paracetamol is worthy of clinical evaluation. [ABSTRACT FROM AUTHOR]

1. The aim of the present study was to test the hypothesis that increasing GABAergic neurotransmission is involved in the prevention or treatment of brain oedema. The study was conducted in the well-established rat triethyltin (TET) model of brain oedema and examined the effects of etifoxine, a compound that increases GABAergic neurotransmission through multiple mechanisms, including neurosteroid synthesis. 2. Daily oral administration of 3 mg/kg per day TET for 5 consecutive days strongly perturbed rat behaviour and induced reproducible cerebral oedema. Coadministration of etifoxine (2 × 25 or 2 × 50 mg/kg per day, p.o.) over the 5 days of TET treatment blocked the development of brain oedema and the increase in brain sodium content induced by TET, as well as reducing the increase in brain chloride content. Moreover, etifoxine inhibited the decrease in bodyweight, the neurological deficit and the altered locomotor activity induced by TET. At a lower dose (2 ↔ 10 mg/kg per day, p.o.), etifoxine did not have any preventive effects. 3. To examine the curative effects of etifoxine, it was administered from the 4th day of TET treatment for 5 consecutive days, when brain oedema was already established. In these experiments, etifoxine (2 ↔ 50 mg/kg per day, p.o.) significantly reduced cerebral oedema and the outcomes induced by TET treatment. Moreover, etifoxine reduced the mortality in response to TET treatment. 4. In conclusion, because etifoxine has a good safety profile as an anxiolytic, the results of the present study suggest that it is worth further clinical investigation as a neuroprotectant. [ABSTRACT FROM AUTHOR]

This article studies the role of white, black and mulatto women during the last two years of the Haitian War of Independence, also known as the Haitian Revolution (1802–04). It might be expected that women's contribution was limited in wartime, but this article concludes otherwise. Desirable women were sought as prizes symbolic of a man's status in colonial society, or actively used their appeal to obtain political favours. Women of colour contributed to the rebellion in the fields of logistics, espionage and even combat. They also experienced martyrdom when convicted of aiding the rebel army. White women, in turn, were considered such an integral part of the colonial order that the rebels, led by Toussaint Louverture and Jean-Jacques Dessalines, targeted them, as well as other civilians, during the fighting, then proceeded to exterminate all surviving whites after the rebel victory. [ABSTRACT FROM AUTHOR]

Examines the capability and the analytical quality of three different in vivo methods for measuring skin hydration. Overview of water content in human skin; Percentage of water content of skin; Content of live epidermis; Discussion on the results of the study.

The longnose dace ( Rhinichthys cataractae) appears as a relevant model to address environmental and ecological issues in an evolutionary perspective. Eleven microsatellite markers were characterized for this species. Eight of these loci were highly polymorphic for populations of this species. Between four to 10 loci were also successfully amplified in five closely related species. These markers are believed to be valuable tools for genetic analysis of populations of longnose dace and other Leuciscinae species. [ABSTRACT FROM AUTHOR]

Purpose: To compare the anti-inflammatory effect of topical diclofenac sodium 0.1% in a fixed combination with gentamicin 0.3% to the anti-inflammatory effect of dexamethasone phosphate 0.1% in a prospective randomized double-masked double-dummy study in patients undergoing cataract surgery. Setting: Trial performed from June 1991 to April 1992 at the Hôpital Jules Gonin, Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland. Methods: Inclusion of patients scheduled for extracapsular cataract extraction (ECCE) with implantation of an all PMMA intraocular lens (IOL). Double-masked comparison of post-operative inflammation in two randomized treatment groups: (1) fixed diclofenac sodium 0.1%/gentamicin 0.3% and vehicle drops 4X/day until day 12–14 and diclofenac sodium 0.1% 3X/day until day 28. (2) dexamethasone phosphate 0.1% drops 4X/day until postoperative day 12–14 and 3X/day until day 28 and gentamicin 0.3% drops 4X/day until day 12–14. Anterior chamber flare and cells, measured by laser flare-cell photometry, were analyzed as the primary outcomes. Results: Eighty-seven patients were recruited, 45 being assigned to the diclofenac group and 42 to the dexamethasone control group. Diclofenac was significantly better than dexamethasone at controlling flare at day 3 (p≤0.01) and day 12–14 (p≤0.002). Mean anterior chamber cells were also significantly lower at day 12–14 (p≤0.021) and day 28 (p≤0.012). The commonest adverse event was transient punctate keratitis, which occurred in 15 diclofenac and 3 dexamethasone patients. Conclusions: While both treatments were effective at controlling post-operative inflammation, the diclofenac-gentamicin combination followed by diclofenac alone was significantly better at suppressing flare and cells but showed a slightly higher incidence of punctate keratitis and eye discomfort. [ABSTRACT FROM AUTHOR]

Recent advances in genomics, proteomics, and structural biology raised the general need for significant amounts of pure recombinant protein (r-protein). Because of the difficulty in obtaining in some cases proper protein folding in bacteria, several methods have been established to obtain large amounts of r-proteins by transgene expression in mammalian cells. We have developed three nonviral DNA transfer protocols for suspension-adapted HEK-293 and CHO cells: (1) a calcium phosphate based method (Ca-Pi), (2) a calcium-mediated method called Calfection, and (3) a polyethylenimine-based method (PEI). The first two methods have already been scaled up to 14 L and 100 L for HEK-293 cells in bioreactors. The third method, entirely serum-free, has been successfully applied to both suspension-adapted CHO and HEK-293 cells. We describe here the application of this technology to the transient expression in suspension cultivated HEK-293 EBNA cells of some out of more than 20 secreted r-proteins, including antibodies, dimeric proteins, and tagged proteins of various complexity. Most of the proteins were expressed from different plasmid vectors within 5-10 days after the availability of the DNA. Transfections were successfully performed from the small scale (1 mL in 12-well microtiter plates) to the 2 L scale. The results reported made it possible to establish an optimized cell culture and transfection protocol that minimizes batch-to-batch variations in protein expression. The work presented here proves the applicability and robustness of transient transfection technology for the expression of a variety of recombinant proteins.