Presymptomatic geographical distribution of ALS patients suggests the involvement of environmental factors in the disease pathogenesis.

BACKGROUND: Given that the pathogenetic process of ALS begins many years prior to its clinical onset, examining patients' residential histories may offer insights on the disease risk factors. Here, we analyzed the spatial distribution of a large ALS cohort in the 50 years preceding the disease onset. METHODS: Data from the PARALS register were used. A spatial cluster analysis was performed at the time of disease onset and at 1-year intervals up to 50 years prior to that. RESULTS: A total of 1124 patients were included. The analysis revealed a higher-incidence cluster in a large area (435,000 inhabitants) west of Turin. From 9 to 2 years before their onset, 105 cases were expected and 150 were observed, resulting in a relative risk of 1.49 (P = 0.04). We also found a surprising high number of patients pairs (51) and trios (3) who lived in the same dwelling while not being related. Noticeably, these occurrences were not observed in large dwellings as we would have expected. The probability of this occurring in smaller buildings only by chance was very low (P = 0.01 and P = 0.04 for pairs and trios, respectively). CONCLUSIONS: We identified a higher-incidence ALS cluster in the years preceding the disease onset. The cluster area being densely populated, many exposures could have contributed to the high incidence ALS cluster, while we could not find a shared exposure among the dwellings where multiple patients had lived. However, these findings support that exogenous factors are likely involved in the ALS pathogenesis.

How heat stress conditions affect milk yield, composition, and price in Italian Holstein herds.

An edited data set of 700 bulk and 46,338 test-day records collected between 2019 and 2021 in 42 Holstein-dominated farms in the Veneto Region (North of Italy) was available for the present study. Information on protein, fat and lactose content, somatic cell count, and somatic cell score was available in bulk milk as well as individual test-day records, whereas urea concentration (mg/dL), differential somatic cell count (%), and milk yield (kg/d) were available for test-day records only. Milk features were merged with meteorological data retrieved from 8 weather stations located maximum 10 km from the farms. The daily and weekly temperature-humidity index (THI; wTHI) and maximum daily (MTHI) and weekly temperature-humidity index were associated with each record to evaluate the effect of heat stress conditions on milk-related traits through linear mixed models. Least squares means were estimated to evaluate the effect of THI and, separately, of MTHI on milk characteristics correcting for conventional systematic factors. Overall, heat stress conditions lowered the quality of both bulk milk and test-day records, with fat and protein content being greatly reduced, and somatic cell score and differential somatic cell count augmented. Milk yield was not affected by either THI or MTHI in this data set, but the effect of elevated THI and MTHI was in general stronger on test-day records than on bulk milk. Farm-level economic losses of reduced milk quality rather than reduced yield as consequence of elevated THI or MTHI was estimated to be between $23.57 and $43.98 per farmer per day, which is of comparable magnitude to losses resulting from reduced production. Furthermore, MTHI was found to be a more accurate indicator of heat stress experienced by a cow, explaining more variability of traits compared with THI. The negative effect of heat stress conditions on quality traits commences at lower THI/MTHI values compared with milk yield. Thus, a progressive farmers' income loss due to climatic changes is already a reality and it is mainly due to deterioration of milk quality rather than quantity in the studied area.

Grazing affects metabolic pattern of individual cow milk.

Effective traceability tools able to characterize milk from pasture are important to safeguard low-input farming systems, niche dairy products, and local traditions. The aims of the present study were to investigate the ability of proton nuclear magnetic resonance (1H NMR) spectroscopy to discriminate between milk produced from cows before and after the beginning of the grazing season, and to assess the effects of grazing on milk metabolites. The research trial involved a single alpine holding with 72 lactating cows. Individual milks were repeatedly sampled from the same animals before (i.e., d -3 and -1) and after (i.e., d 2, 3, 7, 10, and 14) the onset of the grazing period. One-dimensional 1H NMR spectra of milk extracts were collected through a Bruker spectrometer. Random forest discriminant analysis was applied to 1H NMR spectra to predict the period of collection for each sample. Data concerning the relative abundance of milk metabolites were analyzed through a linear mixed model, which included the fixed effects of period of sampling, cow breed, stage of lactation, and parity, and the random effect of cow nested within breed. The random forest model exhibited great accuracy (93.1%) in discriminating between samples collected on d -3, -1, 2, and 3 and those collected on d 7, 10, and 14. Univariate analysis performed on the 40 detected metabolites highlighted that milk samples from pasture had lower levels of 14 compounds (with fumarate being the most depressed metabolite) and greater levels of 15 compounds (with methanol and hippurate being the most elevated metabolites). Results indicate that milk 1H NMR spectra are promising to identify milk produced in different conditions. Also, our study highlights that grazing is associated with significant changes of milk metabolic profile, suggesting the potential use of several metabolites as indicators of farm management.

The main pulse of the Siberian Traps expanded in size and composition.

Emplacement of large volumes of (sub)volcanic rocks during the main pulse of the Siberian Traps occurred within <1 m.y., coinciding with the end-Permian mass extinction. Volcanics from outside the main Siberian Traps, e.g. Taimyr and West Siberia, have since long been correlated, but existing geochronological data cannot resolve at a precision better than ~5 m.y. whether (sub)volcanic activity in these areas actually occurred during the main pulse or later. We report the first high precision U-Pb zircon geochronology from two alkaline ultramafic-felsic layered intrusive complexes from Taimyr, showing synchronicity between these and the main Siberian Traps (sub)volcanic pulse, and the presence of a second Dinerian-Smithian pulse. This is the first documentation of felsic intrusive magmatism occurring during the main pulse, testifying to the Siberian Trap's compositional diversity. Furthermore, the intrusions cut basal basalts of the Taimyr lava stratigraphy hence providing a minimum age of these basalts of 251.64 ± 0.11 Ma. Synchronicity of (sub)volcanic activity between Taimyr and the Siberian Traps imply that the total area of the Siberian Traps main pulse should include a ~300 000 km2 area north of Norilsk. The vast aerial extent of the (sub)volcanic activity during the Siberian Traps main pulse may explain the severe environmental consequences.

Adult stem cells in the healing of fractures and bone grafts / Células-madre adultas en la cicatrización de fracturas e injertos óseos

ABSTRACT The traumatic accidents which result in fractures and even in impairment of a bone segment have a high prevalence in routine veterinary surgery. Many times these fractures are complex and difficulty healing or need bone grafts to preserve and restore the length of the affected limb. Thus, the recovery time of these animals is usually delicate and long, with complications risks, such as delayed union and non-union of the fractured bone segments or absence of graft incorporation. In this sense, the stem cells (SC) have shown to be a strong ally of the orthopedic doctors due to their capacity to provide osteoprogenitor cells, to increase the osteoinductive effect minimize the healing time and provide a greater efficiency to the repairing process. Due to that, before the expectation of their assignments, this review aims to describe the stem cells characteristics, their current applications in the fractures healing and, especially, their contribution to the bone grafts consolidation.

RESUMEN Los accidentes traumáticos que resultan en fracturas y hasta en el comprometimiento de un segmento óseo tienen alta prevalencia en la rutina quirúrgica veterinaria. Muchas veces esas fracturas son complejas y presentan dificultades de cicatrización o necesitan de injertos óseos para preservar y restaurar el largo del miembro acometido. De esa forma, el tiempo de recuperación de esos animales suele ser delicado y prolongado con riegos de complicaciones, como unión retardada y no unión de los segmentos óseos fracturados o ausencia de incorporación de los injertos. En este sentido, las células-madre (CT) vienen demostrando ser una fuerte aliada de los ortopedistas debido a su capacidad en proveer células osteoprogenitoras, de incrementar el efecto osteoinductor, minimizar el tiempo de cicatrización y proporcionar mayor eficiencia al proceso reparador. Frente a la expectativa de sus atribuciones, la presente revisión tiene por objetivo describir las características de las células-madre, sus aplicaciones actuales en la cicatrización de fracturas y, especialmente, su contribución en la consolidación de injertos óseos.

A 3-year interval is too short for re-screening women testing negative for human papillomavirus: a population-based cohort study.

OBJECTIVE: To compare the results from an initial negative human papillomavirus (HPV) test with re-screening after 3 years in women attending two HPV-based screening programmes. DESIGN: Population-based cohort study. SETTING: Two cervical service screening programmes in Italy. POPULATION: Women aged 25-64 years invited to screening from April 2009 to October 2015. METHODS: Eligible women were invited to undergo an HPV test. Those with a negative HPV test went on to the next screening round 3 years later. Cytology triage was performed for HPV+ (HPV by Hybrid Capture 2) samples, with immediate colposcopy (if abnormal) and HPV re-testing 1 year later (if negative). MAIN OUTCOME MEASURES: Participation rate, positivity at HPV and at triage, referral rate to colposcopy, positive predictive value for cervical intraepithelial neoplasia grade 2+ (CIN2+) at colposcopy, and detection rate for CIN2+. RESULTS: We present the results from 48 751 women at the first screening and 22 000 women at re-screening 3 years later. The response rate was slightly higher at the second screening (74.5 versus 72.1% at the first screening; referral rate, RR 1.11; 95% confidence interval, 95% CI, 1.07-1.14). Compared with the first screening, we observed a significant reduction at the second screening in terms of HPV positivity (RR 0.55, 95% CI 0.51-0.60), referral rate to colposcopy (RR 0.47, 95% CI 0.41-0.53), CIN2+ detection rate (RR 0.24, 95% CI 0.13-0.39), and positive predictive value (PPV) for CIN2+ at colposcopy (RR 0.51, 95% CI 0.29-0.87). CONCLUSIONS: The very low frequency of disease and inadequate PPV at colposcopy indicate that a 3-year interval after a negative HPV test is too short. TWEETABLE ABSTRACT: Three years after a negative HPV the frequency of cervical disease is so low that re-screening is inefficient.

Prospective study of the burden of acute gastroenteritis and rotavirus gastroenteritis in children less than 5 years of age, in Padova, Italy.

BACKGROUND: Data on the burden of rotavirus gastroenteritis in Europe are needed to help understand the potential impact of introducing new rotavirus vaccines. MATERIALS AND METHODS: As part of prospective observational study (Rotavirus gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in Public Health and Society Study, REVEAL) conducted in 2004--2005 in seven European countries, we studied, the characteristics of acute gastroenteritis and rotavirus gastroenteritis in children less than 5 years in primary care, emergency room and hospital settings (Padova, Italy). RESULTS: A total of 757 children with acute gastroenteritis were included and enzyme-linked immunoabsorbent assay (ELISA) results were available for 725 cases. The overall estimated annual incidence for rotavirus gastroenteritis was 4.7%. Overall, rotavirus gastroenteritis was estimated to account for 43.6% of acute gastroenteritis cases. Among children with acute gastroenteritis (AGE) aged 6-23 months, 61.2% were rotavirus positive. Rotavirus gastroenteritis (RVGE) was responsible for 68.8% of hospitalizations, 61% of emergency consultations, and 33% of primary care consultations. The most prevalent serotype was G9 (84.4%) followed by G1 (11.8%). The relative risk for rotavirus gastroenteritis of being referred to hospital after an initial consultation in primary care was 3.37 (95% CI: 1.77-6.43) and 3.38 (95% CI: 2.28-5.01) for emergency room referral. Children with rotavirus gastroenteritis generally had more severe disease than children with rotavirus-negative gastroenteritis. CONCLUSION: Rotavirus accounts for a significant proportion of acute gastroenteritis cases in children less than 5 years in Italy, many of whom require frequent primary care consultations, or care in emergency room or hospital settings.