Photodynamic therapy improves skin antisepsis as a prevention strategy in arthroplasty procedures: A pilot study

Background: Current standard skin antisepsis to prevent surgical site infections are ineffective to eradicate all skin-colonizing bacteria. Photodynamic therapy (PDT) has shown bactericidal effects in vitro, but no clinical study with improvements in skin antisepsis has been documented. Methods: We investigated the effect of methyl aminolevulinate (MAL)-PDT versus no PDT for skin antisepsis treatment (povidone-iodine/alcohol) in the groin of 10 healthy participants. Skin swabs were taken at baseline, immediately after PDT, and after skin antisepsis treatment to cultivate bacteria. At day 7 and 21, bacterial cultures were repeated before and after antisepsis treatment without PDT. Skin biopsies were performed to examine the grade of inflammation. Results: Skin-colonizing bacteria were found in all 20 participants at baseline sampling. Immediately after MAL-PDT, skin was sterile in 7 (70%) participants before and in all 10 (100%) participants after skin antisepsis treatment. In contrast, we found skin-colonizing bacteria in 5 (50%) participants of the control group receiving only skin antisepsis. After 7 and 21 days, skin sterility was similar to the baseline. We observed slight perivascular inflammation with lymphocytes and eosinophils without changes in the histomorphology of eccrine or sebaceous glands in skin biopsies. PDT was generally well tolerated except for localized redness. Conclusion: MAL-PDT with skin antisepsis treatment sterilized skin immediately after its use but did not maintain sterility 7-21 days post-treatment. Due to local side effects, further clinical studies with less intensive PDT conditions or other photosensitizers are needed before PDT is integrated into clinical practice

Histone H2A C-terminus regulates chromatin dynamics, remodeling, and histone H1 binding

The tails of histone proteins are central players for all chromatin-mediated processes. Whereas the N-terminal histone tails have been studied extensively, little is known about the function of the H2A C-terminus. Here, we show that the H2A C-terminal tail plays a pivotal role in regulating chromatin structure and dynamics. We find that cells expressing C-terminally truncated H2A show increased stress sensitivity. Moreover, both the complete and the partial deletion of the tail result in increased histone exchange kinetics and nucleosome mobility in vivo and in vitro. Importantly, our experiments reveal that the H2A C-terminus is required for efficient nucleosome translocation by ISWI-type chromatin remodelers and acts as a novel recognition module for linker histone H1. Thus, we suggest that the H2A C-terminal tail has a bipartite function: stabilisation of the nucleosomal core particle, as well as mediation of the protein interactions that control chromatin dynamics and conformation.publishe

The impact of surgical strategy and rifampin on treatment outcome in Cutibacterium periprosthetic joint infections.

BACKGROUND Cutibacterium species are common pathogens in periprosthetic joint infections (PJI). These infections are often treated with β-lactams or clindamycin as monotherapy, or in combination with rifampin. Clinical evidence supporting the value of adding rifampin for treatment of Cutibacterium PJI is lacking. MATERIALS/METHODS In this multicenter retrospective study, we evaluated patients with Cutibacterium PJI. The primary endpoint was clinical success, defined by the absence of infection relapse or new infection within a minimal follow-up of 12 months. We used Fisher's exact tests and Cox proportional hazards models to analyze the effect of rifampin and other factors on clinical success after PJI. RESULTS We included 187 patients (72.2% male, median age 67 years) with a median follow-up of 36 months. The surgical intervention was two-stage exchange in 95 (50.8%), one-stage exchange in 51 (27.3%), debridement and implant retention (DAIR) in 34 (18.2%), and explantation without reimplantation in 7 (3.7%). Rifampin was included in the antibiotic regimen in 81 (43.3%) cases. Infection relapse occurred in 28 (15.0%), and new infection in 13 (7.0%) cases. In the time-to-event analysis, DAIR (adjusted HR=2.15, p=0.03) and antibiotic treatment over 6 weeks (adjusted HR=0.29, p=0.0002) significantly influenced treatment failure. We observed a tentative evidence for a beneficial effect of adding rifampin to the antibiotic treatment - though not statistically significant for treatment failure (adjusted HR=0.5, p=0.07) and not for relapses (adjusted HR=0.5, p=0.10). CONCLUSIONS We conclude that a rifampin combination is not markedly superior in Cutibacterium PJI but a dedicated prospective multicenter study is needed

Availability, affordability and stock-outs of commodities for the treatment of snakebite in kenya

BACKGROUND: Annually, about 2.7 million snakebite envenomings occur globally. Alongside antivenom, patients usually require additional care to treat envenoming symptoms and antivenom side effects. Efforts are underway to improve snakebite care, but evidence from the ground to inform this is scarce. This study, therefore, investigated the availability, affordability, and stock-outs of antivenom and commodities for supportive snakebite care in health facilities across Kenya. METHODOLOGY/PRINCIPAL FINDINGS: This study used an adaptation of the standardised World Health Organization (WHO)/Health Action International methodology. Data on commodity availability, prices and stock-outs were collected in July-August 2020 from public (n = 85), private (n = 36), and private not-for-profit (n = 12) facilities in Kenya. Stock-outs were measured retrospectively for a twelve-month period, enabling a comparison of a pre-COVID-19 period to stock-outs during COVID-19. Affordability was calculated using the wage of a lowest-paid government worker (LPGW) and the impoverishment approach. Accessibility was assessed combining the WHO availability target (≥80%) and LPGW affordability (<1 day's wage) measures. Overall availability of snakebite commodities was low (43.0%). Antivenom was available at 44.7% of public- and 19.4% of private facilities. Stock-outs of any snakebite commodity were common in the public- (18.6%) and private (11.7%) sectors, and had worsened during COVID-19 (10.6% versus 17.0% public sector, 8.4% versus 11.7% private sector). Affordability was not an issue in the public sector, while in the private sector the median cost of one vial of antivenom was 14.4 days' wage for an LPGW. Five commodities in the public sector and two in the private sector were deemed accessible. CONCLUSIONS: Access to snakebite care is problematic in Kenya and seemed to have worsened during COVID-19. To improve access, efforts should focus on ensuring availability at both lower- and higher-level facilities, and improving the supply chain to reduce stock-outs. Including antivenom into Universal Health Coverage benefits packages would further facilitate accessibility

Histone H2A C-terminus regulates chromatin dynamics, remodeling, and histone H1 binding.

The tails of histone proteins are central players for all chromatin-mediated processes. Whereas the N-terminal histone tails have been studied extensively, little is known about the function of the H2A C-terminus. Here, we show that the H2A C-terminal tail plays a pivotal role in regulating chromatin structure and dynamics. We find that cells expressing C-terminally truncated H2A show increased stress sensitivity. Moreover, both the complete and the partial deletion of the tail result in increased histone exchange kinetics and nucleosome mobility in vivo and in vitro. Importantly, our experiments reveal that the H2A C-terminus is required for efficient nucleosome translocation by ISWI-type chromatin remodelers and acts as a novel recognition module for linker histone H1. Thus, we suggest that the H2A C-terminal tail has a bipartite function: stabilisation of the nucleosomal core particle, as well as mediation of the protein interactions that control chromatin dynamics and conformation

Effect of cow parity and synchronization method with PGF2α on conception rates of Bos indicus cows in Cameroon

The objective of this work was to evaluate the effect of two synchronization methods with prostaglandins F2α (PGF2α) on heifers and multiparous cows. Fourty-three Bos indicus cows (white and Red Fulani) were divided into four groups in a two-by-two factorial structure, parity x method of synchronization. The synchronization methods consisted of a two-dose regime which involved injection of animals on day 0 with PGF2α (Lutalyse) at 5 ml per cow intramuscularly. On day 11, the injection was repeated at the same dosage. On day 14 (72 h after the second injection), a fixed-time artificial insemination (AI) was done. On day 15 (96 h after the second injection), a second insemination was done. The one-and-a-half-dose regime consisted of an injection similar to the first treatment mentioned above on day 0. Thereafter, cows were observed for heat, and anyone showing heat was inseminated. A second dose was given on day 11 to all animals not having shown any heat. A fixed-time AI was done on days 14 and 15. Blood samples were collected on the day 0 of insemination for each cow while day 11 and day 21 after insemination. Progesterone was analysed by means of standard ELISA progesterone kits to determine its profiles after insemination. Results show no evidence of the effect of treatments on conception rates (P>0.05). Similarly, heifers and multiparous cows had similar conception rates (P>0.05). Between 3 weeks and 3 months of pregnancy, there was a loss of embryos of 28 % in heifers and 20 % in multiparous cows, but the difference between the two groups was not significant (P>0.05). It recommended that farmers do not synchronize animals with poor body condition score (BCS). They should also monitor weight gains of heifers, remove them from the herd when they have been mixed with young growing bulls and put them in a breeding herd. The two-dose regime is better to be used in areas where the inseminator cannot easily be available.http://link.springer.com/journal/112502016-01-31hb201

X-Ray Structure of Acid-Sensing Ion Channel 1–Snake Toxin Complex Reveals Open State of a Na+-Selective Channel

SummaryAcid-sensing ion channels (ASICs) detect extracellular protons produced during inflammation or ischemic injury and belong to the superfamily of degenerin/epithelial sodium channels. Here, we determine the cocrystal structure of chicken ASIC1a with MitTx, a pain-inducing toxin from the Texas coral snake, to define the structure of the open state of ASIC1a. In the MitTx-bound open state and in the previously determined low-pH desensitized state, TM2 is a discontinuous α helix in which the Gly-Ala-Ser selectivity filter adopts an extended, belt-like conformation, swapping the cytoplasmic one-third of TM2 with an adjacent subunit. Gly 443 residues of the selectivity filter provide a ring of three carbonyl oxygen atoms with a radius of ∼3.6 Å, presenting an energetic barrier for hydrated ions. The ASIC1a-MitTx complex illuminates the mechanism of MitTx action, defines the structure of the selectivity filter of voltage-independent, sodium-selective ion channels, and captures the open state of an ASIC

Low rates of immediate coronary angiography among young adults resuscitated from sudden cardiac arrest

International audienceAim: Coronary artery disease (CAD) has recently been emphasized as a major cause of sudden cardiac arrest (SCA) in young adults. We aim to assess the rate of immediate coronary angiography performance in young patients resuscitated from SCA.Methods: From May 2011 to May 2017, all cases of out-of-hospital SCA aged 18-40 years alive at hospital admission were prospectively included in 48 hospitals of the Great Paris area. Cardiovascular causes of SCA were centrally adjudicated, and management including immediate coronary angiography performance was assessed.Results: Out of 3579 SCA admitted alive, 409 (11.4%) patients were under 40 years of age (32.3 ± 6.2 years, 69.7% males), with 244 patients having a definite cause identified. Among those, CAD accounted for 72 (29.5%) cases, of which 64 (88.9%) were acute coronary syndromes. The rate of immediate coronary angiography was only 41.7% compared to 65.1% among those ≥40-years (P < 0.001). During the study period, while the rate of immediate coronary angiography increased from 60.5% to 70.3% (P < 0.001) in patients aged ≥40 years, the rate in patients aged less than 40 years remained stable (43.5% to 45.3%, P = 0.795). Patients younger than 40 years were significantly less likely to undergo immediate coronary angiography (OR = 0.34, 95% CI: 0.25-0.47), although early angiography was associated with survival at hospital discharge (OR = 2.68, 95% CI: 1.21-6.00).Conclusion: CAD is the first cause of SCA in young adults aged less than 40 years. The observed low rates of immediate coronary angiography suggest a missed opportunity for early intervention

Characteristics and clinical assessment of unexplained sudden cardiac arrest in the real-world setting: focus on idiopathic ventricular fibrillation

International audienceAims: Recent studies have shown that in more than half of apparently unexplained sudden cardiac arrests (SCA), a specific aetiology can be unmasked by a careful evaluation. The characteristics and the extent to which such cases undergo a systematic thorough investigation in real-life practice are unknown.Methods and results: Data were analysed from an ongoing study, collecting all cases of out-of-hospital cardiac arrest in Paris area. Investigations performed during the index hospitalization or planned after discharge were gathered to evaluate the completeness of assessment of unexplained SCA. Between 2011 and 2016, among the 18 622 out-of-hospital cardiac arrests, 717 survivors (at hospital discharge) fulfilled the definition of cardiac SCA. Of those, 88 (12.3%) remained unexplained after electrocardiogram, echocardiography, and coronary angiography. Cardiac magnetic resonance imaging yielded the diagnosis in 25 (3.5%) cases, other investigations accounted for 14 (2.4%) additional diagnoses, and 49 (6.8%) patients were labelled as idiopathic ventricular fibrillation (IVF) (48.7 ± 15 years, 69.4% male). Among those labelled IVF, only 8 (16.3%) cases benefited from a complete workup (including pharmacological testing). Younger patients [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.80-22.26] and those admitted to university centres (OR 3.60, 95% CI 1.12-12.45) were more thoroughly investigated. Genetic testing and family screening were initiated in only 9 (18.4%) and 12 (24.5%) cases, respectively.Conclusion: Our findings suggest that complete investigations are carried out in a very low proportion of unexplained SCA. Standardized, systematic approaches need to be implemented to ensure that opportunities for specific therapies and preventive strategies (including relatives) are not missed