Enfriamiento al inicio de verano para mitigar el estrés por calor en vacas Holstein del noroeste de México

The objective of this study was to determine the physiological, endocrine and productive response in lactating dairy cows under several series of artificial cooling at the beginning of the summer (June to July, 2011). Fourteen multiparous Holstein cows were assigned in one of two treatments: Cooling (C) before milking (0700 and 1700 h) and additional cooling (AC) each 2 h (from 0700 to 1700h) in the holding pen of the milking parlor. Milk yield (MY), and serum levels of prolactin (PRL) and IGF1 were measured. Rectal temperature and respiratory rate were registered and included as physiological markers of heat stress. Ambient temperature and relative humidity were also collected and used to calculate temperature-humidity index (THI). Both markers of heat stress showed a significant interaction (P<0.001) between treatment and time/week, which were lower in AC treatment (-3.8 breaths per minute and -0.2 °C) during wk 6 and 7. Serum levels of PRL were higher under additional cooling (AC: 35.1 vs C: 29.4 ng/ml; P=0.004), while  IGF1 serum levels showed variation only through the sampling weeks (P=0.014). The MY increased (P<0.05) in AC only during wk 6 (+3.1 kg/d) and 7 (+3.1 kg/d). It was concluded that additional cooling at the beginning of the summer reduced heat stress in dairy cows allowing a better productive performance at the end of the study because such effect relied on the variable time/week.El objetivo de este estudio fue determinar la respuesta fisiológica, endócrina y productiva en vacas lactantes sometidas a varias series de enfriamiento artificial al inicio de verano (junio a julio de 2011). Se asignaron 14 vacas Holstein multíparas a uno de dos tratamientos: enfriamiento (E) antes de la ordeña (0700 y 1700 h) y enfriamiento adicional (EA) cada 2 h de 0700 a 1700 h en el corral de espera a la ordeña. Se midió la producción de leche (PL), niveles de prolactina (PRL) e IGF1, mientras que la temperatura rectal y frecuencia respiratoria fueron registradas y consideradas como indicadores fisiológicos de estrés por calor. La temperatura ambiental y humedad relativa también fueron registradas y utilizadas para calcular el índice de temperatura-humedad (ITH). Los indicadores de estrés calórico mostraron una interacción significativa (P<0.001) entre tratamiento y tiempo/semana, los cuales fueron menores con EA (-3.8 respiraciones por minuto y -0.2 °C) sólo durante las semanas 6 y 7. Los niveles séricos de PRL fueron mayores bajo enfriamiento adicional (EA: 35.1 vs E: 29.4 ng/ml; P=0.004), mientras que los de IGF1 solo variaron a través de las semanas de muestreo (P=0.014). La PL se incrementó (P<0.05) en EA durante las semanas 6 (+3.1kg/día) y 7 (+3.1 kg/día). Se concluye que la mayor frecuencia de baños mitigó la condición de estrés calórico al inicio de verano, permitiéndole a la vaca expresar un mejor desempeño productivo al final del estudio, ya que dicho efecto dependió de la variable tiempo/semana

Quantitative informant- and self-reports of subjective cognitive decline predict amyloid beta PET outcomes in cognitively unimpaired individuals independently of age and APOE ε4

Introduction: Amyloid beta (Aβ) pathology is an Alzheimer's disease early hallmark. Here we assess the value of longitudinal self- and informant reports of cognitive decline to predict Aβ positron emission tomography (PET) outcome in cognitively unimpaired middle-aged individuals. Methods: A total of 261 participants from the ALFA+ study underwent [18F]flutemetamol PET and Subjective Cognitive Decline Questionnaire (SCD-Q) concurrently, and 3 years before scan. We used logistic regressions to evaluate the ability of SCD-Q scores (self and informant) to predict Aβ PET visual read, and repeated analysis of variance to assess whether changes in SCD-Q scores relate to Aβ status. Results: Self-perception of decline in memory (odds ratio [OR] = 1.2), and informant perception of executive decline (OR = 1.6), increased the probability of a positive scan. Informant reports 3 years before scanning predicted Aβ PET outcome. Longitudinal increase of self-reported executive decline was predictive of Aβ in women (P = .003). Discussion: Subjective reports of cognitive decline are useful to predict Aβ and may improve recruitment strategies

Epidemiological and Clinical Complexity of Amoxicillin-Clavulanate- Resistant Escherichia coli

Two hundred twelve patients with colonization/infection due to amoxicillin-clavulanate (AMC)-resistant Escherichia coli were studied. OXA-1- and inhibitor-resistant TEM (IRT)-producing strains were associated with urinary tract infections, while OXA-1 producers and chromosomal AmpC hyperproducers were associated with bacteremic infections. AMC resistance in E. coli is a complex phenomenon with heterogeneous clinical implications

Spanish Multicenter Study of the Epidemiology and Mechanisms of Amoxicillin-Clavulanate Resistance in Escherichia coli

We conducted a prospective multicenter study in Spain to characterize the mechanisms of resistance to amoxicillin-clavu-lanate (AMC) in Escherichia coli. Up to 44 AMC-resistant E. coli isolates (MIC>32/16 g/ml) were collected at each of theseven participant hospitals. Resistance mechanisms were characterized by PCR and sequencing. Molecular epidemiology was studied by pulsed-field gel electrophoresis (PFGE) and by multilocus sequence typing. Overall AMC resistance was 9.3%. The resistance mechanisms detected in the 257 AMC-resistant isolates were OXA-1 production (26.1%), hyperpro-duction of penicillinase (22.6%), production of plasmidic AmpC (19.5%), hyperproduction of chromosomic AmpC(18.3%), and production of inhibitor-resistant TEM (IRT) (17.5%). The IRTs identified were TEM-40 (33.3%), TEM-30(28.9%), TEM-33 (11.1%), TEM-32 (4.4%), TEM-34 (4.4%), TEM-35 (2.2%), TEM-54 (2.2%), TEM-76 (2.2%), TEM-79(2.2%), and the new TEM-185 (8.8%). By PFGE, a high degree of genetic diversity was observed although two well-defined clusters were detected in the OXA-1-producing isolates: the C1 cluster consisting of 19 phylogroup A/sequence type 88[ST88] isolates and the C2 cluster consisting of 19 phylogroup B2/ST131 isolates (16 of them producing CTX-M-15). Each of the clusters was detected in six different hospitals. In total, 21.8% of the isolates were serotype O25b/phylogroup B2 (O25b/B2). AMC resistance in E. coli is widespread in Spain at the hospital and community levels. A high prevalence of OXA-1 was found. Although resistant isolates were genetically diverse, clonality was linked to OXA-1-producing isolates of the STs 88 and 131. Dissemination of IRTs was frequent, and the epidemic O25b/B2/ST131 clone carried many different mechanisms of AMC resistance

GENYOi005-A: An induced pluripotent stem cells (iPSCs) line generated from a patient with Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM) carrying a p.Thr196Ala variant

Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM) is a rare platelet disorder caused by mutations in RUNX1. We generated an iPSC line (GENYOi005-A) from a FPDMM patient with a non-previously reported variant p.Thr196Ala. Non-integrative Sendai viruses expressing the Yamanaka reprogramming factors were used to reprogram peripheral blood mononuclear cells from this FPDMM patient. Characterization of GENYOi005-A included genetic analysis of RUNX1 locus, Short Tandem Repeats profiling, alkaline phosphatase enzymatic activity, expression of pluripotency-associated factors and differentiation studies in vitro and in vivo. This iPSC line will provide a powerful tool to study developmental alterations of FPDMM patientsThis work was supported by the Ramon y Cajal (RYC-2015-18382) to PJR founded by the Ministry of Economy and Competitiveness; the Instituto de Salud Carlos III-FEDER (CP12/03175 and CPII17/00032) to V.R-M., (PI17/01311) to M.L.L and J.R., (PI17/01966; Fundación Mutua Madrileña AP172142019; Premio Lopez Borrasca SETH 2019; GRS2061/A/19) to J.M.B. and (CPII15/00018 and PI16/01340) to PJR; by the Chair "Doctors Galera-Requena in cancer stem cell research" (CMC-CTS963) to J.A.M. and C.G-L

Neuropilin 1 balances β8 integrin-activated TGFβ signaling to control sprouting angiogenesis in the brain

© 2015. Published by The Company of Biologists Ltd. Angiogenesis in the developing central nervous system (CNS) is regulated by neuroepithelial cells, although the genes and pathways that couple these cells to blood vessels remain largely uncharacterized. Here, we have used biochemical, cell biological and molecular genetic approaches to demonstrate that β8 integrin (Itgb8) and neuropilin 1 (Nrp1) cooperatively promote CNS angiogenesis by mediating adhesion and signaling events between neuroepithelial cells and vascular endothelial cells. β8 integrin in the neuroepithelium promotes the activation of extracellular matrix (ECM)-bound latent transforming growth factor β (TGFβ) ligands and stimulates TGFβ receptor signaling in endothelial cells. Nrp1 in endothelial cells suppresses TGFβ activation and signaling by forming intercellular protein complexes with β8 integrin. Cell type-specific ablation of β8 integrin, Nrp1, or canonical TGFβ receptors results in pathological angiogenesis caused by defective neuroepithelial cell-endothelial cell adhesion and imbalances in canonical TGFβ signaling. Collectively, these data identify a paracrine signaling pathway that links the neuroepithelium to blood vessels and precisely balances TGFβ signaling during cerebral angiogenesis

Pre-pandemic Alzheimer Disease Biomarkers and Anxious-Depressive Symptoms During the COVID-19 Confinement in Cognitively Unimpaired Adults

BACKGROUND AND OBJECTIVES: Increased anxious-depressive symptomatology is observed in the preclinical stage of Alzheimer's disease (AD), which may accelerate disease progression. We investigated whether amyloid-β, cortical thickness in medial temporal lobe structures , neuroinflammation and sociodemographic factors were associated with greater anxious-depressive symptoms during the COVID-19 confinement. METHODS: This retrospective observational study included cognitively unimpaired older adults from the ALFA (Alzheimer and FAmilies) cohort, the majority with a family history of sporadic AD. Participants performed the Hospital Anxiety and Depression Scale (HADS) during the COVID-19 confinement. A subset had available retrospective (on average: 2.4 years before) HADS assessment, amyloid [18F] flutemetamol PET and structural MRI scans and CSF markers of neuroinflammation (interleukin-6 [IL-6], triggering receptor expressed on myeloid cells 2 and glial fibrillary acidic protein levels). We performed multivariable linear regression models to investigate the associations of pre-pandemic AD-related biomarkers and sociodemographic factors with HADS scores during the confinement. We further performed an analysis of covariance in order to adjust by participants' pre-pandemic anxiety-depression levels . Finally, we explored the role of stress and lifestyle changes (sleep patterns, eating, drinking, smoking habits, and medication use) on the tested associations and performed sex-stratified analyses. RESULTS: We included 921 (254 with AD biomarkers) participants. Amyloid-β positivity (B=3.73; 95%CI=1.1 to 6.36; p=.006), caregiving (B=1.37; 95%CI=0.24 to 2.5; p=.018), sex (women: B=1.95; 95%CI=1.1 to 2.79; p<.001), younger age (B=-0.12; 95%CI=-0.18 to -0.052; p<.001) and lower education (B=-0.16; 95%CI=-0.28 to -0.042; p=.008) were associated with greater anxious-depressive symptoms during the confinement. Considering pre-pandemic anxiety-depression levels, we further observed an association between lower levels of CSF IL-6 (B=-5.11; 95%CI=-10.1 to -0.13; p=.044) and greater HADS scores. The results were independent of stress-related variables and lifestyle changes. Stratified analysis revealed that the associations were mainly driven by women. DISCUSSION: Our results link AD-related pathophysiology and neuroinflammation with greater anxious-depressive symptomatology during the COVID-19-related confinement, notably in women. AD pathophysiology may increase neuropsychiatric symptomatology in response to stressors. This association may imply a worse clinical prognosis in people at risk for AD after the pandemic, and thus deserves to be considered by clinicians. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier NCT02485730