Exploring Predictive Factors for Potentially Avoidable Emergency Department Transfers: Findings From the FINE Study.

OBJECTIVES: To assess the prevalence of potentially avoidable transfers (PAT) and identify factors associated with these transfers to emergency departments (EDs) among nursing home (NH) residents. DESIGN: This is a secondary outcome analysis of the FINE study, a multicenter observational study collecting data on NH residents, NH settings, and contextual factors of ED transfers. SETTINGS AND PARTICIPANTS: NHs in the former Midi-Pyrénées region of the southwest of France (n = 312); a total of 1037 NH residents who experienced ED transfers (n = 1017) between January 2016 and December 2016. METHODS: The analysis included resident baseline characteristics and NH and transfer decision-making characteristics. An expert group categorized the transfer status as either PAT or unavoidable. Multivariable analysis using a mixed logistic model, accounting for intra-NH correlation, was conducted to assess factors independently associated with PAT. RESULTS: Among 1017 included transfers, 87.02% (n = 885) were identified as PAT and 12.98% (n = 132) unavoidable transfers. Multivariable analysis revealed that the following patient-related factors were associated with a likely high rate of PAT: usual behavior disturbances before transfer, including productive trouble (OR 2.04, 95% CI 1.25-3.33; P = .0044) and unusual symptom of falling during the week preceding the transfer (OR 4.55, 95% CI 1.76-11.82; P = .0019). On the other hand, distance between ED and NH (OR 0.98, 95% CI 0.97-0.998; P = .0231), NH staff trained in palliative care in the last 3 years (OR 0.52, 95% CI 0.29-0.95; P = .0324), the impossibility of direct hospitalization to an appropriate unit (OR 0.54, 95% CI 0.34-0.87; P = .0117), and the resident Charlson Comorbidity Index (OR 0.90, 95% CI 0.82-0.99; P = .0369) were associated with a lower probability of PAT. CONCLUSION AND IMPLICATIONS: Transfers from NHs to hospital EDs were frequently potentially avoidable, meaning that there are still significant opportunities to reduce PAT. Our findings may help to specifically identify interventions that should be targeted at both NH and resident levels.

Implementation of the WHO integrated care for older people (ICOPE) programme in clinical practice: a prospective study.

BACKGROUND: The INSPIRE integrated care for older people (ICOPE)-CARE programme is a public health programme implementing the ICOPE health-care pathway in clinical practice. The primary objective of this study was to describe the large-scale implementation and feasibility of the INSPIRE ICOPE-CARE guidelines in clinical practice. The secondary aims were to describe the characteristics of patients who were identified as positive for abnormalities in intrinsic capacity (ie, locomotion, cognition, psychology, vitality, hearing, and vision) during step 1, and to describe the prevalence of these positive screenings. METHODS: In this prospective study, we evaluated a real-life population of users of primary care services in the Occitania region (France). Participants who were aged 60 years and older and lived in a community were eligible for inclusion in our study. Individuals aged ≥60 years were screened (step 1) by health-care providers or through self-assessments using digital tools (the ICOPE MONITOR app and the ICOPEBOT conversational robot). Our implementation strategy involved raising awareness among health-care professionals about the WHO ICOPE programme, training professionals in the ICOPE-CARE guidelines, and developing a digital infrastructure (ie, digital tools, a database, and a remote ICOPE monitoring platform). The feasibility of implementing the INSPIRE ICOPE-CARE guidelines was determined by the anticipated inclusion of ≥10 000 participants, and having a follow-up rate of over 50%. FINDINGS: Between Jan 1, 2020, and November 18, 2021, 10 903 older people (mean age 76·0, SD 10·5 years; 6627 [60·8%] of whom were women) had a baseline step 1 screening done, and 5185 (70·4%) of 7367 eligible participants had a 6-month follow-up of step 1 screening. 10 285 (94·3%) participants had a positive intrinsic capacity result during screening at baseline. 958 (9·3%) participants were evaluated with step 2 (in-depth assessments). Positive intrinsic capacity was confirmed in 865 (90·3%) participants. Most recommendations in step 3 (care plan) were related to locomotion, vitality, and cognition. INTERPRETATION: The high number of participants included in our study, as well as the high rates of follow-up, provides evidence to suggest that the large-scale implementation of ICOPE in clinical practice is feasible. The very high prevalence of positive screening for impaired intrinsic capacity during step 1, as well as the high rates of confirmed deficits in intrinsic capacity during step 2, suggest that the INSPIRE ICOPE-CARE programme is able to target individuals who are at increased risk for functional loss and disability. FUNDING: Occitania Regional Health Agency, Region Occitanie and Pyrénées-Méditerranée, European Regional Development Fund, and The Interreg Program V-A Spain-France-Andorra.

Reply to Inzitari et al. Comment on "Blancafort Alias et al. A Multi-Domain Group-Based Intervention to Promote Physical Activity, Healthy Nutrition, and Psychological Wellbeing in Older People with Losses in Intrinsic Capacity: AMICOPE Development Study. Int. J. Environ. Res. Public Health 2021, 18, 5979".

This is a reply to the comment by Inzitari et al [...].

Preservation of Mimosa tenuiflora Antiaflatoxigenic Activity Using Microencapsulation by Spray-Drying.

Mimosa tenuiflora aqueous extract (MAE) is rich in phenolic compounds. Among them, condensed tannins have been demonstrated to exhibit a strong antioxidant and antiaflatoxin B1 activities in Aspergillus flavus. Since antioxidant capacity can change with time due to environmental interactions, this study aimed to evaluate the ability of encapsulation by spray-drying of Mimosa tenuiflora aqueous extract to preserve their biological activities through storage. A dry formulation may also facilitate transportation and uses. For that, three different wall materials were used and compared for their efficiency. Total phenolic content, antioxidant activity, antifungal and antiaflatoxin activities were measured after the production of the microparticles and after one year of storage at room temperature. These results confirmed that encapsulation by spray-drying using polysaccharide wall materials is able to preserve antiaflatoxin activity of Mimosa tenuiflora extract better than freezing.

[Step 1 screening: experimentation in Occitania with nurses and pharmacists]. / Le dépistage step 1 : expérimentation en Occitanie avec les infirmiers et les pharmaciens.

Screening with the step 1 tool is the principal modality of entry into the ICOPE program. This preliminary step is particularly an initiative of primary care health professionals, who are daily caring older people. In Occitania, as part of the deployment of ICOPE program, nurses and pharmacists, were invited to integrate the step 1 in their practices. They benefited, if they wished, from a free webinar training.

A Multi-Domain Group-Based Intervention to Promote Physical Activity, Healthy Nutrition, and Psychological Wellbeing in Older People with Losses in Intrinsic Capacity: AMICOPE Development Study.

The World Health Organization has developed the Integrated Care of Older People (ICOPE) strategy, a program based on the measurement of intrinsic capacity (IC) as "the composite of all physical and mental attributes on which an individual can draw". Multicomponent interventions appear to be the most effective approach to enhance IC and to prevent frailty and disability since adapted physical activity is the preventive intervention that has shown the most evidence in the treatment of frailty and risk of falls. Our paper describes the development of a multi-domain group-based intervention addressed to older people living in the community, aimed at improving and/or maintaining intrinsic capacity by means of promoting physical activity, healthy nutrition, and psychological wellbeing in older people. The process of intervention development is described following the Guidance for reporting intervention development studies in health research (GUIDED). The result of this study is the AMICOPE intervention (Aptitude Multi-domain group-based intervention to improve and/or maintain IC in Older PEople) built upon the ICOPE framework and described following the Template for Intervention Description and Replication (TIDieR) guidelines. The intervention consists of 12 face-to-face sessions held weekly for 2.5 h over three months and facilitated by a pair of health and social care professionals. This study represents the first stage of the UK Medical Research Council framework for developing and evaluating a complex intervention. The next step should be carrying out a feasibility study for the AMICOPE intervention and, at a later stage, assessing the effectiveness in a randomized controlled trial.

Mimosa tenuiflora Aqueous Extract: Role of Condensed Tannins in Anti-Aflatoxin B1 Activity in Aspergillus flavus.

Aflatoxin B1 (AFB1) is a potent carcinogenic mycotoxin that contaminates numerous crops pre- and post-harvest. To protect foods and feeds from such toxins without resorting to pesticides, the use of plant extracts has been increasingly studied. The most interesting candidate plants are those with strong antioxidative activity because oxidation reactions may interfere with AFB1 production. The present study investigates how an aqueous extract of Mimosa tenuiflora bark affects both the growth of Aspergillus flavus and AFB1 production. The results reveal a dose-dependent inhibition of toxin synthesis with no impact on fungal growth. AFB1 inhibition is related to a down-modulation of the cluster genes of the biosynthetic pathway and especially to the two internal regulators aflR and aflS. Its strong anti-oxidative activity also allows the aqueous extract to modulate the expression of genes involved in fungal oxidative-stress response, such as msnA, mtfA, atfA, or sod1. Finally, a bio-guided fractionation of the aqueous extract demonstrates that condensed tannins play a major role in the anti-aflatoxin activity of Mimosa tenuiflora bark.

Factors Associated with Potentially Inappropriate Transfer to the Emergency Department among Nursing Home Residents.

OBJECTIVES: To determine the factors associated with the potentially inappropriate transfer of nursing home (NH) residents to emergency departments (EDs) and to compare hospitalization costs before and after transfer of individuals addressed inappropriately vs those addressed appropriately. DESIGN: Multicenter, observational, case-control study. SETTING AND PARTICIPANTS: 17 hospitals in France, 1037 NH residents. MEASURES: All NH residents transferred to the 17 public hospitals' EDs in southern France were systematically included for 1 week per season. An expert panel composed of family physicians, emergency physicians, geriatricians, and pharmacists defined whether the transfer was potentially inappropriate or appropriate. Residents' and NHs' characteristics and contextual factors were entered into a mixed logistic regression to determine factors associated independently with potentially inappropriate transfers. Hospital costs were collected in the national health insurance claims database for the 6 months before and after the transfer. RESULTS: A total of 1037 NH residents (mean age 87.2 ± 7.1, 68% female) were transferred to the ED; 220 (21%) transfers were considered potentially inappropriate. After adjustment, anorexia [odds ratio (OR) 2.41, 95% confidence interval (CI) 1.57-3.71], high level of disability (OR 0.90, 95% CI 0.81-0.99), and inability to receive prompt medical advice (OR 1.67, 95% CI 1.20-2.32) were significantly associated with increased likelihood of potentially inappropriate transfers. The existence of an Alzheimer's disease special care unit in the NH (OR 0.66, 95% CI 0.48-0.92), NH staff trained on advance directives (OR 0.61, 95% CI 0.41-0.89), and calling the SAMU (mobile emergency medical unit) (OR 0.47, 95% CI 0.34-0.66) were significantly associated with a lower probability of potentially inappropriate transfer. Although the 6-month hospitalization costs prior to transfer were higher among potentially inappropriate transfers compared with appropriate transfers (€6694 and €4894, respectively), transfer appropriateness was not significantly associated with hospital costs. CONCLUSIONS AND IMPLICATIONS: Transfers from NHs to hospital EDs were frequently appropriate. Transfer appropriateness was conditioned by NH staff training, access to specialists' medical advice, and calling the SAMU before making transfer decisions. TRIAL REGISTRATION: clinicaltrials.gov, NCT02677272.

In vitro Evaluation of the Nutraceutical Potential of Theobroma cacao pod Husk and Leaf Extracts for Small Ruminants.

PURPOSE: Some agroindustrial by-products could be used as nutraceutical materials for small ruminants helping with their nutrition while controlling their gastrointestinal nematodes. This study evaluated the potential in vitro nutraceutical value of pod husks and leaves of three varieties of Theobroma cacao using two Haemonchus contortus isolates with different polyphenol susceptibility. METHODS: Leaves and husks from three T. cacao varieties (AZT, CAL and CEY) were evaluated for their bromatological composition, in vitro dry matter digestibility and polyphenol content. Acetone:water extracts (70:30) of each plant variety were evaluated using the egg hatch and larval exsheathment inhibition tests, using two isolates (FESC and PARAISO) of H. contortus. Effective concentrations 50% (EC50) were determined for both tests. The role of polyphenols was confirmed using polyvinylpolypyrrolidone. L3 exposed to CAL leaf extract were submitted to transmission electron microscopy. RESULTS: Both plant materials showed a good nutritional value to complement protein-rich diets for small ruminants. Extracts inhibited exsheathment of H. contortus L3 more effectively than the egg hatching, and the leaf extracts were more active than husk extracts in the L3 exsheathment inhibition. The FESC isolate was more sensitive to extracts. Polyphenols blocked exsheathment inhibition of leaf extracts. Structural damage was observed in the sheath and muscles of L3 exposed to CAL leaf extracts. CONCLUSION: The two T. cacao materials tested showed their potential to be used as ruminant feeds. Extracts affected H. contortus by blocking L3 exsheathment, particularly with the leaf extracts. The in vivo nutraceutical value should be confirmed in small ruminants.

Does Biological Denitrification Inhibition (BDI) in the Field Induce an Increase in Plant Growth and Nutrition in Apium graveolens L. Grown for a Long Period?

Intensive agriculture uses a lot of nitrogen fertilizers to increase crop productivity. These crops are in competition with soil-denitrifying microorganisms that assimilate nitrogen in the form of nitrate and transform it into N2O, a greenhouse gas, or N2. However, certain plant species exude secondary metabolites, called procyanidins, which inhibit denitrifiers and increase the nitrate pool in the soil available for plant nutrition. This phenomenon is called biological denitrification inhibition. Previously, we showed that the addition of exogenous procyanidins to a lettuce crop induces denitrifier inhibition and increases nitrate content in the soil, affecting lettuce morphological traits. Here, the effects of procyanidin amendments in the field on a more long-term and nitrogen-consuming crop species such as celery were tested. The effects of procyanidin amendment on celery growth with those of conventional ammonium nitrate amendments were, therefore, compared. Denitrification activity, nitrate concentration, the abundance of denitrifying bacteria in the soil, and traits related to celery growth were measured. It was shown that the addition of procyanidins inhibits denitrifiers and increases the soil nitrate level, inducing an improvement in celery morphological traits. In addition, procyanidin amendment induces the lowest nitrogen concentration in tissues and reduces N2O emissions.

Nor-cucurbitacins from the leaves of Mareya micrantha (Benth.) Müll. Arg. (Euphorbiaceae).

Mareya micrantha, an Ivoirian medicinal plant, was investigated for its chemical constituents and antioxidant properties. This study carried out on the hydroethanolic extract of the leaves led to three new nor-cucurbitacins named: 29-nor-1,2,3,4,5,10-dehydro-3,15α,20ß-trihydroxy-16α-acetyl-11,22-dioxo-cucurbita-23-ene 2-O-ß-D-glucopyranoside (1), 29-nor-2ß,20ß,25-trihydroxy-16α-acetyl-3,11,22-trioxo-cucurbita-4,23-diene (2) and 29-nor-2ß,15α,20ß-trihydroxy-16α-acetyl-3,11,22-trioxo-cucurbita-4,23-diene 2-O-ß-D-glucopyranoside (3). The structures were established on the basis of spectral data (NMR, UV, MS and IR). The antioxidant properties evaluated by DPPH and CUPRAC methods gave the best activity with compound 1. The chemotaxonomic significance of the isolation of these compounds in Mareya micrantha, a species belonging to the Euphorbiaceae family, is discussed.

Bio-guided fractionation to identify Senegalia gaumeri leaf extract compounds with anthelmintic activity against Haemonchus contortus eggs and larvae.

Small ruminants browsing in tropical forests readily consume the foliage of Senegalia gaumeri. A S. gaumeri methanol:water extract was recently shown to have ovicidal activity against Haemonchus contortus eggs in vitro. In the present study, the fraction of a S. gaumeri methanol:water extract with ovicidal activity against H. contortus eggs and the metabolites potentially involved in this activity were identified. Bio-guided fractionation of the S. gaumeri methanol:water extract identified high ovicidal activity (80.29%, EC50 = 58.9 µg/mL) in the non-polar sub-fraction P1. Gas chromatography-mass spectrometry (GC-MS) identified several fatty acids: pentacosane (18.05%), heneicosane (18.05%), triacontane (30.94%), octacosane (18.05%), and hexanedioic acid bis-(2-ethylhexyl) ester (32.72%). Purification of the polar components of sub-fraction P1 led to the identification of p-coumaric acid as a major constituent. In egg hatch tests, 400 µg/mL p-coumaric acid resulted in an ovicidal effect of 8.7%, a larvae failing eclosion effect of 2.9%, and of the emerged larvae (88.4%), many were damaged. In conclusion, the low AH activity of p-coumaric acid against H. contortus eggs indicates that it is not solely responsible for the ovicidal activity of sub-fraction P1 but might act in synergy with other compounds in this fraction. However, p-coumaric acid showed potential anthelmintic effects against the larval stage of H. contortus.

Rational Drug Design of Topically Administered Caspase 1 Inhibitors for the Treatment of Inflammatory Acne.

The use of an interleukin ß antibody is currently being investigated in the clinic for the treatment of acne, a dermatological disorder affecting 650M persons globally. Inhibiting the protease responsible for the cleavage of inactive pro-IL1ß into active IL-1ß, caspase-1, could be an alternative small molecule approach. This report describes the discovery of uracil 20, a potent (38 nM in THP1 cells assay) caspase-1 inhibitor for the topical treatment of inflammatory acne. The uracil series was designed according to a published caspase-1 pharmacophore model involving a reactive warhead in P1 for covalent reversible inhibition and an aryl moiety in P4 for selectivity against the apoptotic caspases. Reversibility was assessed in an enzymatic dilution assay or by using different substrate concentrations. In addition to classical structure-activity-relationship exploration, topical administration challenges such as phototoxicity, organic and aqueous solubility, chemical stability in solution, and skin metabolic stability are discussed and successfully resolved.

Factors predisposing nursing home resident to inappropriate transfer to emergency department. The FINE study protocol.

BACKGROUND: Each year, around one out of two nursing home (NH) residents are hospitalized in France, and about half to the emergency department (ED). These transfers are frequently inappropriate. This paper describes the protocol of the FINE study. The first aim of this study is to identify the factors associated with inappropriate transfers to ED. METHODS/DESIGN: FINE is a case-control observational study. Sixteen hospitals participate. Inclusion period lasts 7 days per season in each center for a total period of inclusion of one year. All the NH residents admitted in ED during these periods are included. Data are collected in 4 times: before transfer in the NH, at the ED, in hospital wards in case of patient's hospitalization and at the patient's return to NH. The appropriateness of ED transfers (i.e. case versus control NH residents) is determined by a multidisciplinary team of experts. RESULTS: Our primary objective is to determine the factors predisposing NH residents to inappropriate transfer to ED. Our secondary objectives are to assess the cost of the transfers to ED; study the evolution of NH residents' functional status and the psychotropic and inappropriate drugs prescription between before and after the transfer; calculate the prevalence of potentially avoidable transfers to ED; and identify the factors predisposing NH residents to potentially avoidable transfer to ED. DISCUSSION: A better understanding of the determinant factors of inappropriate transfers to ED of NH residents may lead to proposals of recommendations of better practice in NH and would allow implementing quality improvement programs in the health organization.

Improving the Quality of Care of Long-Stay Nursing Home Residents in France.

The aim of the Impact d'une démarche QUAlité sur l'évolution des pratiques et le déclin fonctionnel des Résidents en Établissement d'hébergement pour personnes âgées dépendantes (IQUARE) study was to examine the effects of a global intervention comprising professional support and education for nursing home (NH) staff on quality indicators (QIs) and functional decline and emergency department (ED) transfers of residents. One hundred seventy-five NHs in France (a total of 6,275 residents randomly selected from NHs) volunteered and were enrolled in a nonrandomized controlled multicenter individually customize trial with 18-month follow-up. NHs were allocated to a quality audit and feedback intervention (control group: 90 NHs, 3,258 residents) or to the quality audit and feedback intervention plus collaborative work meetings between a hospital geriatrician and NH staff (experimental group: 85 NHs, 3,017 residents). At the NH level, prevalence of assessment of kidney function, cognitive function, risk of pressure ulcers, behavioral disturbances, depression, pain, weight measurement, and transfer to the ED were recorded. Ability to perform basic activities of daily living was assessed at the resident level. At baseline, NH QIs were generally low (with large standard deviations), and annual rate of transfer to the ED was high (~20%) and similar in both groups. The intervention had a significant positive effect on the prevalence of assessment of pressure ulcer risk, depression, pain, and prevalence of ED transfers. It had no significant effect on functional decline. Large-scale efforts to improve QIs involving collaboration between hospital and NH providers and based on audit and collaborative discussion are feasible and improve some aspects of quality of care in NHs.

The nursing home effect: a case study of residents with potential dementia and emergency department visits.

OBJECTIVES: The burden of potential dementia cases without formal diagnosis on the health care system is almost unknown. This study examined the impact of potential dementia without formal diagnosis on the rate of visits to hospital emergency department (ED) of nursing home (NH) residents. DESIGN: Cross-sectional study. SETTING: NHs (175) located in France. PARTICIPANTS: A total of 5684 subjects who were living in the NH for at least 1 year. MEASUREMENTS: Information on NHs' characteristics and on NH residents' health was recorded by NH staff. Participants were divided in 3 groups according to their dementia status: diagnosed dementia, potential dementia without formal diagnosis, and nondementia. The outcome measure was a binary variable: ED visits in the last 12 months (yes vs no). A mixed-effects logistic regression was performed on ED visits accounting for the random effects of living in a particular NH. RESULTS: From the 5684 participants, 1036 had been seen in the ED. Adjusted odds ratio (AOR) showed that having a potential dementia without formal diagnosis, compared with a diagnosed dementia, was associated with an increased probability of ED visits (AOR = 1.25, 95% confidence interval: 0.99-1.59, P = .061); however, when a random NH effect was entered into the model, the association between potential dementia without formal diagnosis and ED visits disappeared (AOR = 1.22, 95% confidence interval: 0.95-1.57, P = .11). CONCLUSION: The association of potential dementia without formal diagnosis with ED visits varies across NHs. This intra-NH aspect (eg, organization and care habits) should be taken into account when examining the rates of hospitalization and possibly the use of health care services in general among NH residents.

Indicators of benzodiazepine use in nursing home residents in France: a cross-sectional study.

OBJECTIVES: Little information is available about associations between nursing home (NH) structural and organizational aspects and benzodiazepine prescriptions, particularly for long-acting drugs. This study addressed this knowledge gap. DESIGN: Cross-sectional study. SETTING: One hundred seventy-five NHs from France. PARTICIPANTS: A total of 6275 NH residents, aged 86 years (± 8.2), and mostly women (73.7%). MEASUREMENTS: Outcome measures were: (1) benzodiazepine and (2) long-acting benzodiazepine use. NH staff sent to research team all drug prescriptions in the week participants were included in the study; staff also recorded information on residents' characteristics, and NHs structure and internal organization. Binary logistic regressions were performed separately on total and long-acting benzodiazepine. RESULTS: A total of 3350 persons took benzodiazepine; 577 took long-acting benzodiazepine. Subject-related characteristics were the main correlates of benzodiazepine use. NH characteristics were also related to this outcome: number of beds ≥ 91 (Odds Ratio (OR) 0.820, 95% Confidence Interval (CI) 0.682-0.986), special care unit (OR 1.131, 95% CI 1.000-1.279), pharmacy for internal usage (OR 1.341, 95%CI 1.128-1.594), and date records of the first prescription of psychotropics (OR 1.394, 95% CI 1.209-1.607). Pharmacy for internal usage was also associated with long-acting benzodiazepine (OR 1.374, 95% CI 1.076-1.754). CONCLUSIONS: NH structure- and organization-related indicators impact benzodiazepine use among NH residents. This finding is of particular importance because these indicators are more easily modifiable than subject-related characteristics. Therefore, NH directors and medical staff should be aware about this to implement feasible modifications for reducing inappropriate and chronic benzodiazepine use.

Prevalence and associations of the use of proton-pump inhibitors in nursing homes: a cross-sectional study.

OBJECTIVES: Very scarce information is available about the use of proton-pump inhibitors (PPI) in nursing homes (NH). This study investigated the factors associated with PPI use among NH residents. DESIGN: Cross-sectional SETTING: One hundred seventy-five NHs in Midi-Pyrénées region, South-Western France. PARTICIPANTS: Data was collected for 6275 NH residents. Participants (73.7% women) were aged 86 years (± 8.2). MEASUREMENTS: NH staff sent participants' drug prescriptions to research team; they also recorded information on residents' health characteristics. A binary logistic regression was performed on PPI use. RESULTS: PPI use was highly prevalent (n = 2 370, ie, 37.8%). Whilst peptic ulcer (OR 4.741; 95% CI 3.647-6.163) and nonsteroidal anti-inflammatory drugs (OR 2.124; 95% CI 1.528-2.951) were important indicators of PPI use, they explained just a small fraction of PPI prescriptions; most prescriptions were probably inappropriately related to a general condition of health vulnerability, reflected by polypharmacy and comorbidities. CONCLUSIONS: Vulnerable people take PPIs more often in NHs. Physicians must be aware about the health risks possibly induced by inappropriate PPI use when prescribing these drugs for NH residents.

Endothelial cell-derived bone morphogenetic proteins control proliferation of neural stem/progenitor cells.

Neurogenesis persists in the adult brain subventricular zone where neural stem/progenitor cells (NSPCs) lie close to brain endothelial cells (BECs). We show in mouse that BECs produce bone morphogenetic proteins (BMPs). Coculture of embryonic and adult NSPCs with BECs activated the canonical BMP/Smad pathway and reduced their proliferation. We demonstrate that coculture with BECs in the presence of EGF and FGF2 induced a reversible cell cycle exit of NSPCs (LeX+) and an increase in the amount of GFAP/LeX-expressing progenitors thought to be stem cells. Levels of the phosphatidylinositol phosphatase PTEN were upregulated in NSPCs after coculture with BECs, or treatment with recombinant BMP4, with a concomitant reduction in Akt phosphorylation. Silencing Smad5 with siRNA or treatment with Noggin, a BMP antagonist, demonstrated that upregulation of PTEN in NSPCs required BMP/Smad signaling and that this pathway regulated cell cycle exit of NSPCs. Therefore, BECs may provide a feedback mechanism to control the proliferation of NSPCs.

Fanconi DNA repair pathway is required for survival and long-term maintenance of neural progenitors.

Although brain development abnormalities and brain cancer predisposition have been reported in some Fanconi patients, the possible role of Fanconi DNA repair pathway during neurogenesis is unclear. We thus addressed the role of fanca and fancg, which are involved in the activation of Fanconi pathway, in neural stem and progenitor cells during brain development and adult neurogenesis. Fanca(-/-) and fancg(-/-) mice presented with microcephalies and a decreased neuronal production in developing cortex and adult brain. Apoptosis of embryonic neural progenitors, but not that of postmitotic neurons, was increased in the neocortex of fanca(-/-) and fancg(-/-) mice and was correlated with chromosomal instability. In adult Fanconi mice, we showed a reduced proliferation of neural progenitor cells related to apoptosis and accentuated neural stem cells exhaustion with ageing. In addition, embryonic and adult Fanconi neural stem cells showed a reduced capacity to self-renew in vitro. Our study demonstrates a critical role for Fanconi pathway in neural stem and progenitor cells during developmental and adult neurogenesis.