Traumatic brain injury promotes neurogenesis at the cost of astrogliogenesis in the adult hippocampus of male mice.

Traumatic brain injury (TBI) can result in long-lasting changes in hippocampal function. The changes induced by TBI on the hippocampus contribute to cognitive deficits. The adult hippocampus harbors neural stem cells (NSCs) that generate neurons (neurogenesis), and astrocytes (astrogliogenesis). While deregulation of hippocampal NSCs and neurogenesis have been observed after TBI, it is not known how TBI may affect hippocampal astrogliogenesis. Using a controlled cortical impact model of TBI in male mice, single cell RNA sequencing and spatial transcriptomics, we assessed how TBI affected hippocampal NSCs and the neuronal and astroglial lineages derived from them. We observe an increase in NSC-derived neuronal cells and a concomitant decrease in NSC-derived astrocytic cells, together with changes in gene expression and cell dysplasia within the dentate gyrus. Here, we show that TBI modifies NSC fate to promote neurogenesis at the cost of astrogliogenesis and identify specific cell populations as possible targets to counteract TBI-induced cellular changes in the adult hippocampus.

Assessment of fish protein hydrolysate as a substitute for fish meal in white shrimp diets: Impact on growth, immune response, and resistance against Vibrio parahaemolyticus infection.

This study investigated the effects of fish protein hydrolysate derived from barramundi on growth performance, muscle composition, immune response, disease resistance, histology and gene expression in white shrimp (Penaeus vannamei). In vitro studies demonstrated FPH enhanced mRNA expressions of key immune-related genes and stimulated reactive oxygen species (ROS) production and phagocytic activity in shrimp hemocytes. To evaluate the effects of substituting fish meal with FPH in vivo, four isoproteic (43 %), isolipidic (6 %), and isoenergetic diets (489 kcal/100 g) were formulated with fish meal substitution levels of 0 % (control), 30 % (FPH30), 65 % (FPH65), and 100 % (FPH100). After 8-week feeding, the growth performance of FPH65 and FPH100 were significantly lower than that of control and FPH30 (p < 0.05). Similarly, the midgut histological examination revealed the wall thickness and villi height of FPH100 were significantly lower than those of control (p < 0.05). The shrimps were received the challenge of AHPND + Vibrio parahaemolyticus at week 4 and 8. All FPH-fed groups significantly enhanced resistance against Vibrio parahaemolyticus at week 4 (p < 0.05). However, this protective effect diminished after long-period feeding. No significant difference of survival rate was observed among all groups at week 8 (p > 0.05). The expressions of immune-related genes were analyzed at week 4 before and after challenge. In control group, V. parahaemolyticus significantly elevated SOD in hepatopancreas and Muc 19, trypsin, Midline-fas, and GPx in foregut (p < 0.05). Moreover, hepatopancreatic SOD of FPH65 and FPH100 were significantly higher than that of control before challenge (p < 0.05). Immune parameters were measured at week 8. Compared with control, the phagocytic index of FPH 30 was significantly higher (p < 0.05). However, dietary FPH did not alter ROS production, phenoloxidase activity, phagocytic rate, and total hemocyte count (p > 0.05). These findings suggest that FPH30 holds promise as a feed without adverse impacts on growth performance while enhancing the immunological response of white shrimp.

Effects of supplementing coated methionine in a high plant-protein diet on growth, antioxidant capacity, digestive enzymes activity and expression of TOR signaling pathway associated genes in gibel carp, Carassius auratus gibelio.

This study explored the impacts of supplementation of different levels of coated methionine (Met) in a high-plant protein diet on growth, blood biochemistry, antioxidant capacity, digestive enzymes activity and expression of genes related to TOR signaling pathway in gibel carp (Carassius auratus gibeilo). A high-plant protein diet was formulated and used as a basal diet and supplemented with five different levels of coated Met at 0.15, 0.30, 0.45, 0.60 and 0.75%, corresponding to final analyzed Met levels of 0.34, 0.49, 0.64, 0.76, 0.92 and 1.06%. Three replicate groups of fish (initial mean weight, 11.37 ± 0.02 g) (20 fish per replicate) were fed the test diets over a 10-week feeding period. The results indicated that with the increase of coated Met level, the final weight, weight gain (WG) and specific growth rate initially boosted and then suppressed, peaking at 0.76% Met level (P< 0.05). Increasing dietary Met level led to significantly increased muscle crude protein content (P< 0.05) and reduced serum alanine aminotransferase activity (P< 0.05). Using appropriate dietary Met level led to reduced malondialdehyde concentration in hepatopancreas (P< 0.05), improved superoxide dismutase activity (P< 0.05), and enhanced intestinal amylase and protease activities (P< 0.05). The expression levels of genes associated with muscle protein synthesis such as insulin-like growth factor-1, protein kinase B, target of rapamycin and eukaryotic initiation factor 4E binding protein-1 mRNA were significantly regulated, peaking at Met level of 0.76% (P< 0.05). In conclusion, supplementing optimal level of coated Met improved on fish growth, antioxidant capacity, and the expression of TOR pathway related genes in muscle. The optimal dietary Met level was determined to be 0.71% of the diet based on quadratic regression analysis of WG.

New insights into aging in LiNiO2 cathodes from high resolution paramagnetic NMR spectroscopy.

Bulk degradation processes are examined in the LiNiO2 cathode using high resolution solid-state NMR, combined with magnetometry and X-ray diffraction. Capacity decay is correlated with bulk heterogeneity, whereby multiple structural domains coexist in the charged state, and the Li content and electrochemical activity of these domains is unraveled for the first time.

Community-acquired Klebsiella pneumoniae pneumonia in ICU: a multicenter retrospective study.

BACKGROUND: Alongside the recent worldwide expansion of hypervirulent Klebsiella pneumoniae (KP) infections, the available literature regarding cases of community acquired pneumonias (KP-CAP) remains scarce but reports a strikingly high and early mortality. We performed a retrospective multicenter study (7 ICU in France) between 2015 and 2019, comparing prognosis and severity of KP-CAP versus Streptococcus pneumoniae - CAP (SP-CAP). METHODS: For each KP-CAP, three SP-CAP admitted in ICUs within the same center and within the same 6-month window were selected. When available, KP strains were studied, and bacterial virulence was genetically assessed for virulence factors. The primary outcome was in-hospital mortality. Associations between clinical outcomes and type of infection were tested using univariate and multivariate logistic regressions, adjusted for pairing variables. RESULTS: Twenty-seven KP-CAP and 81 SP-CAP were included. Respective in-hospital mortality rates were 59% (n = 16) and 17% (n = 14, p < 0.001), despite adequate antibiotic therapy. KP-CAP median time from admission to death was 26.9 h [IQR 5.75-44 h] and were significantly associated with higher rates of multiple organ failures (93% vs. 42%, p < 0.001), disseminated intravascular coagulation (12% vs. 1.3%, p = 0.046), septic shock (median lactate on ICU admission 4.60 vs. 2.90 mmol/L, p = 0.030) and kidney failure (KDIGO-3: 87% vs. 44%, p < 0.001). Interestingly, alcoholism was the only identified predisposing factor of KP-CAP. Severity on ICU admission (2-fold higher for KP-CAP) was the only factor associated with mortality in a multivariate analysis. CONCLUSION: We described a strong association between KP-CAP infection and higher and earlier mortality when compared to SP-CAP. Moreover, alcoholism was the sole predisposing factor associated with KP-CAP infection. These findings should raise awareness of clinicians involved in the management of severe CAP about this microbiological etiology. Future prospective studies are needed to confirm these results and to design strategies to improve the prognosis of such infections.

Inter-physician Communication in Pediatric Orthopaedics: What do Pediatricians Want to Hear From us?

BACKGROUND: Pediatric orthopaedic surgeons often communicate with general pediatric providers to facilitate patient care, but little data exist on communication preferences. This study investigates pediatric provider preferences regarding when they would like to receive patient updates from pediatric orthopedists, which communication modalities they prefer, and what information they like to receive. METHODS: We developed a 19-question e-mail survey to evaluate provider preferences on communication modality, timing, frequency, and what data they deem important as it relates to musculoskeletal patient care. RESULTS: A total of 111 general pediatric providers in our geographical region completed the survey. Among the providers, 55.9% preferred fax, 40.5% electronic health record inbox message, 19.8% e-mail, 12.6% mail, and 7.2% call/voicemail. The majority (67.9%) preferred information in a traditional note format, whereas 24.8% preferred a summary in paragraph format. Patient diagnosis and treatment plan for shared patients were the most important pieces of information for general pediatric providers to receive from pediatric orthopedists. Of various patient-specific scenarios included in the survey, referrals for osteomyelitis concern, fractures requiring surgery, scoliosis concern, and developmental dysplasia of the hip requiring treatment were considered most important for pediatric orthopedists to send updates. In terms of frequency of communication, over half of the pediatric providers (59.5%) desired updates after the first visit and after care plan changes (50.5%). CONCLUSION: Only 43.5% of pediatric providers feel like current communication with pediatric orthopaedic surgeons is "always" or "often" adequate. Most of our surveyed providers preferred occasional SOAP notes through fax as communication from pediatric orthopaedic surgeons. The communication deemed most important to providers related to referrals where the provider makes the initial diagnosis and then refers the patient to orthopaedics for a condition with potential long-term patient impacts. Finally, providers felt communication was most important after the first pediatric orthopaedic office visit. EVIDENCE: Level III, survey based.

Alpha-ketoglutaric acid mitigates the detrimental effects of soy antigenic protein on the intestinal health and growth performance of Mirror carp Cyprinus carpio.

The study investigated the alleviated effects of Alpha-ketoglutaric acid (AKG) on the intestinal health of mirror carp (Cyprinus carpio Songpu) caused by soy antigenic protein. The diets were formulated from fishmeal (CON), 50% soybean meal (SBM), the mixture of glycinin and ß-conglycinin (11 + 7S) and adding 1% AKG in the 11 + 7S (AKG). Carp (~ 4 g) in triplicate (30 fish per tank) was fed to apparent satiation thrice a day for six weeks. Compared with CON, SBM treatment resulted in significantly poor growth performance (P < 0.05), whereas 11 + 7S and AKG treatments were not significantly different from CON (P > 0.05). Gene expression of tumor necrosis factor (TNF-α) and interleukin-1 ß (IL-1ß) in proximal intestines (PI) and distal intestines (DI) were increased (P < 0.05), and transforming growth factor (TGF-ß) in PI and middle intestines (MI) was decreased (P < 0.05) in both SBM and 11 + 7S. The caspase-3 in DI increased in SBM (P < 0.05) and the caspase-3 and caspase-9 in DI increased in 11 + 7S (P < 0.05); conversely, TGF-ß in PI and MI was increased, TNF-α and IL-1ß in the MI, caspase-3, and caspase-9 in DI was decreased in AKG (P < 0.05). The TOR (target of rapamycin) in PI and MI, ACC in PI, MI and DI was decreased in SBM (P < 0.05), the AMPK in the PI and DI, TOR in PI, MI and DI, ACC in PI and DI, 4E-BP in DI was reduced in 11 + 7S (P < 0.05). AMPK in the PI and DI, ACC in the PI and MI, TOR in PI, MI, and DI, 4E-BP in PI and DI was recovered by AKG supplementation (P < 0.05). Lipids and lipid-like metabolism, organic acids and derivatives metabolism increased in AKG dietary treatment. In conclusion, AKG reduces the expression of intestinal inflammation and apoptosis pathway and changes glycerophospholipid metabolism and sphingolipid metabolism in the intestine of fish.

Effects of Replacing Fish Meal with Enzymatic Cottonseed Protein on the Growth Performance, Immunity, Antioxidation, and Intestinal Health of Chinese Soft-Shelled Turtle (Pelodiscus sinensis).

The dietary effects of replacing fish meal with enzymatic cottonseed protein (ECP) on the growth performance, immunity, antioxidant, and intestinal health of Chinese soft-shelled turtles have not been explored. An eight-week feeding trial was conducted with a quadruplicated group of turtles (3.44 ± 0.01 g) that were randomly assigned to 16 cages (0.6 m × 0.6 m × 0.6 m) with 30 turtles that were stocked in each cage. Four dietary groups were fed with diets supplemented with 0, 2%, 4%, and 6% (ECP0 group (control group), ECP2 group, ECP4 group, ECP6 group) of enzymatic cottonseed protein replacing fishmeal. The present study illustrated that the final weight and WG in the ECP2 and ECP4 groups were significantly increased (P < 0.05) compared with the control group. The ECP2, ECP4, and ECP6 groups significantly reduced the feed coefficient (P < 0.05) and significantly increased the SGR (P < 0.05). The serum TP and ALB of the ECP4 group were significantly increased (P < 0.05). The ECP2, ECP4, and ECP6 groups significantly increased the activity of intestinal pepsin (P < 0.05), and the activity of intestinal lipase of the EPC4 group was significantly increased (P < 0.05). The intestinal villus height of the EPC4 group and EPC6 group, the villus width of the EPC2 group and EPC4 group, and the intestinal muscle thickness of the EPC4 group were significantly increased (P < 0.05). At the same time, replacing fishmeal with enzymatic cottonseed protein also affected the intestinal inflammation-related genes compared with the control group. Besides that, the expression of the IL-10 gene in the experimental group was significantly upregulated (P < 0.05). Nevertheless, the expression of TNF-α and IL-8 genes in the ECP2 group and TNF-α and IL-1ß genes in the ECP4 group was significantly downregulated (P < 0.05). In summary, replacing fish meal with enzymatic cottonseed protein positively affects the growth, immunity, and intestinal health of Chinese soft-shelled turtles. The appropriate proportion of enzymatic cottonseed protein to replace fish meal in turtle feed is 4%.

Amides as modifiable directing groups in electrophilic borylation.

Amide directed C-H borylation using ≥two equiv. of BBr3 forms borenium cations containing a R2N(R')C[double bond, length as m-dash]O→B(Ar)Br unit which has significant Lewis acidity at the carbonyl carbon. This enables reduction of the amide unit to an amine using hydrosilanes. This approach can be applied sequentially in a one-pot electrophilic borylation-reduction process, which for phenyl-acetylamides generates ortho borylated compounds that can be directly oxidised to the 2-(2-aminoethyl)-phenol. Other substrates amenable to the C-H borylation-reduction sequence include mono and diamino-arenes and carbazoles. This represents a simple method to make borylated molecules that would be convoluted to access otherwise (e.g. N-octyl-1-BPin-carbazole). Substituent variation is tolerated at boron as well as in the amide unit, with diarylborenium cations also amenable to reduction. This enables a double C-H borylation-reduction-hydrolysis sequence to access B,N-polycyclic aromatic hydrocarbons (PAHs), including an example where both the boron and nitrogen centres contain functionalisable handles (N-H and B-OH). This method is therefore a useful addition to the metal-free borylation toolbox for accessing useful intermediates (ArylBPin) and novel B,N-PAHs.

Modeling the impact of national and regional lockdowns on the 2020 spring wave of COVID-19 in France.

Several countries have implemented lockdowns to control their COVID-19 epidemic. However, questions like "where" and "when" still require answers. We assessed the impact of national and regional lockdowns considering the French first epidemic wave of COVID-19 as a case study. In a regional lockdown scenario aimed at preventing intensive care units (ICU) saturation, almost all French regions would have had to implement a lockdown within 10 days and 96% of ICU capacities would have been used. For slowly growing epidemics, with a lower reproduction number, the expected delays between regional lockdowns increase. However, the public health costs associated with these delays tend to grow with time. In a quickly growing pandemic wave, defining the timing of lockdowns at a regional rather than national level delays by a few days the implementation of a nationwide lockdown but leads to substantially higher morbidity, mortality, and stress on the healthcare system.

RetroSnake: A modular pipeline to detect human endogenous retroviruses in genome sequencing data.

Human endogenous retroviruses (HERVs) integrated into the human genome as a result of ancient exogenous infections and currently comprise ∼8% of our genome. The members of the most recently acquired HERV family, HERV-Ks, still retain the potential to produce viral molecules and have been linked to a wide range of diseases including cancer and neurodegeneration. Although a range of tools for HERV detection in NGS data exist, most of them lack wet lab validation and they do not cover all steps of the analysis. Here, we describe RetroSnake, an end-to-end, modular, computationally efficient, and customizable pipeline for the discovery of HERVs in short-read NGS data. RetroSnake is based on an extensively wet-lab validated protocol, it covers all steps of the analysis from raw data to the generation of annotated results presented as an interactive html file, and it is easy to use by life scientists without substantial computational training. Availability and implementation: The Pipeline and an extensive documentation are available on GitHub.

Synthesis of Electrophiles Derived from Dimeric Aminoboranes and Assessing Their Utility in the Borylation of π Nucleophiles.

Dimeric aminoboranes, [H2BNR2]2 (R = Me or CH2CH2) containing B2N2 cores, can be activated by I2, HNTf2 (NTf2 = [N(SO2CF3)2]), or [Ph3C][B(C6F5)4] to form isolable H2B(µ-NR2)2BHX (for X = I or NTf2). For X = [B(C6F5)4]- further reactivity, presumably between [H2B(µ-NMe2)2BH][B(C6F5)4] and aminoborane, forms a B3N3-based monocation containing a three-center two electron B-(µ-H)-B moiety. The structures of H2B(µ-NMe2)2BH(I) and [(µ-NMe2)BH(NTf2)]2 indicated a sterically crowded environment around boron, and this leads to the less common O-bound mode of NTf2 binding. While the iodide congener reacted very slowly with alkynes, the NTf2 analogues were more reactive, with hydroboration of internal alkynes forming (vinyl)2BNR2 species and R2NBH(NTf2) as the major products. Further studies indicated that the B2N2 core is maintained during the first hydroboration, and that it is during subsequent steps that B2N2 dissociation occurs. In the mono-boron systems, for example, i Pr2NBH(NTf2), NTf2 is N-bound; thus, they have less steric crowding around boron relative to the B2N2 systems. Notably, the monoboron systems are much less reactive in alkyne hydroboration than the B2N2-based bis-boranes, despite the former being three coordinate at boron while the latter are four coordinate at boron. Finally, these B2N2 electrophiles are much more prone to dissociate into mono-borane species than pyrazabole [H2B(µ-N2C3H3)]2 analogues, making them less useful for the directed diborylation of a single substrate.

[Minors in a French custody center: Sociodemographic characteristics, global health and vulnerability factors]. / Mineurs en garde à vue: caractéristiques sociodémographiques, auto-évaluation de la santé et identification de facteurs de vulnérabilité.

Minor offenders are at risk for medico-psycho-social vulnerability, that impacts global health, schooling, professional future, and socio-familial environment; moreover, minors who are victims of violence and neglect are at greater risk of becoming offenders and minor offenders are at greater risk of suffering violence. Few data are currently available regarding global health and vulnerability factors for minors (i.e. those aged under 18) who have been placed in police custody. This study aimed to describe the judicial and social characteristics of these minors, their medical and psychological health status, with the hypothesis that most minors placed in police custody can be considered as abused or neglected, by presenting factors of vulnerability. We carried out a prospective study, including consecutive minors aged of 13 to 18 years old, who had been detained in custody at the Central Police Station of Nantes (France), from October 2012 to May 2013. The sociodemographic characteristics, scores for global health and the data collected from the welfare and judiciary services were analyzed, to identify abused or neglected minors. Ninety-nine teenagers were included: 78 males and 11 females (mean age±standard deviation: 16.5 years±1.01), who had been placed in custody for robbery, with a remarkable proportion of recidivist minors. Our study has highlighted several worrying characteristics of minors in police custody reflecting their vulnerability, as living conditions (no schooling, no fixed address) and irregular or absent medical follow-up; however their scores for global health were not different from the general population. While 49 minors (49.5 %) had already been identified by the welfare services, our study find that 35 added minors of this population should nonetheless be considered as being abused and/or neglected, based on a very high rate of minors already followed by child protection services and/or already penalized. Systematic health screening in custody could help to detect abused and/or neglected minors, in order to provide them access to appropriate medical and social cares. They could be referring to psychiatric or rehabilitation cares, and to the relevant welfare and judiciary services in order to assess if a specific protection measure is needed.

Evaluating COVID-19 Booster Vaccination Strategies in a Partially Vaccinated Population: A Modeling Study.

BACKGROUND: Several countries are implementing COVID-19 booster vaccination campaigns. The objective of this study was to model the impact of different primary and booster vaccination strategies. METHODS: We used a compartmental model fitted to hospital admission data in France to analyze the impact of primary and booster vaccination strategies on morbidity and mortality, assuming waning of immunity and various levels of virus transmissibility during winter. RESULTS: Strategies prioritizing primary vaccinations were systematically more effective than strategies prioritizing boosters. Regarding booster strategies targeting different age groups, their effectiveness varied with immunity and virus transmissibility levels. If the waning of immunity affects all adults, people aged 30 to 49 years should be boosted in priority, even for low transmissibility levels. CONCLUSIONS: Increasing the primary vaccination coverage should remain a priority. If a plateau has been reached, boosting the immunity of younger adults could be the most effective strategy, especially if SARS-CoV-2 transmissibility is high.

Two Directing Groups Used for Metal Catalysed Meta-C-H Functionalisation Only Effect Ortho Electrophilic C-H Borylation.

Two templates used in meta-directed C-H functionalisation under metal catalysis do not direct meta-C-H borylation under electrophilic borylation conditions. Using BCl3 only Lewis adduct formation with Lewis basic sites in the template is observed. While combining BBr3 and the template containing an amide linker only led to amide directed ortho C-H borylation, with no pyridyl directed meta borylation. The amide directed borylation is selective for the ortho borylation of the aniline derived unit in the template, with no ortho borylation of the phenylacetyl ring - which would also form a six membered boracycle - observed. In the absence of other aromatics amide directed ortho borylation on to phenylacetyl rings can be achieved. The absence of meta-borylation using two templates indicates a higher barrier to pyridyl directed meta borylation relative to amide directed ortho borylation and suggests that bespoke templates for enabling meta-directed electrophilic borylation may be required.

A modelling study investigating short and medium-term challenges for COVID-19 vaccination: From prioritisation to the relaxation of measures.

BACKGROUND: The roll-out of COVID-19 vaccines is a multi-faceted challenge whose performance depends on pace of vaccination, vaccine characteristics and heterogeneities in individual risks. METHODS: We developed a mathematical model accounting for the risk of severe disease by age and comorbidity, and transmission dynamics. We compared vaccine prioritisation strategies in the early roll-out stage and quantified the extent to which measures could be relaxed as a function of the vaccine coverage achieved in France. FINDINGS: Prioritizing at-risk individuals reduces morbi-mortality the most if vaccines only reduce severity, but is of less importance if vaccines also substantially reduce infectivity or susceptibility. Age is the most important factor to consider for prioritization; additionally accounting for comorbidities increases the performance of the campaign in a context of scarce resources. Vaccinating 90% of ≥65 y.o. and 70% of 18-64 y.o. before autumn 2021 with a vaccine that reduces severity by 90% and susceptibility by 80%, we find that control measures reducing transmission rates by 15-27% should be maintained to remain below 1000 daily hospital admissions in France with a highly transmissible variant (basic reproduction number R0  = 4). Assuming 90% of ≥65 y.o. are vaccinated, full relaxation of control measures might be achieved with a vaccine coverage of 89-100% in 18-64 y.o or 60-69% of 0-64 y.o. INTERPRETATION: Age and comorbidity-based vaccine prioritization strategies could reduce the burden of the disease. Very high vaccination coverage may be required to completely relax control measures. Vaccination of children, if possible, could lower coverage targets necessary to achieve this objective.