Heat stress affects reproductive performance of high producing dairy cows bred in an area of southern Apennines

A 5-year retrospective (from 2008 to 2012) survey was carried out by analyzing data of high producing dairy cows reared in farms located in an area of southern Apennines. The indicators of fertility obtained were related to either season variations or the temperature-humidity index (THI). A significant lower number of conceptions evaluated per month on an annual basis (NCY), i.e., a parameter obtained by subtracting gestation length to the calving date, was found during the summer months; furthermore, this parameter decreased along with THI increase. The number of heats detected varied equally to NCY and represented the main cause of the lower fertility consequent to heat stress (HS). The age at first calving was not significantly affected by either the season or the THI. The mean number of AI/pregnancy in relation to the calving time was significantly affected by the season but it was not related to THI. The number of days open was significantly larger in the animals calved from January to July than from August to December (163±33 vs 123±36 days; P< 0.001); this causes an annual economic loss of several thousand euro in each farm analyzed. In conclusion, HS causes severe economic losses in dairy farms located in southern Apennines that are mainly due to a lower number of heats detected as well as a larger number of days open and semen doses used

Mapping and characterization of G-quadruplexes in Mycobacterium tuberculosis gene promoter regions

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), one of the top 10 causes of death worldwide in 2015. The recent emergence of strains resistant to all current drugs urges the development of compounds with new mechanisms of action. G-quadruplexes are nucleic acids secondary structures that may form in G-rich regions to epigenetically regulate cellular functions. Here we implemented a computational tool to scan the presence of putative G-quadruplex forming sequences in the genome of Mycobacterium tuberculosis and analyse their association to transcription start sites. We found that the most stable G-quadruplexes were in the promoter region of genes belonging to definite functional categories. Actual G-quadruplex folding of four selected sequences was assessed by biophysical and biomolecular techniques: all molecules formed stable G-quadruplexes, which were further stabilized by two G-quadruplex ligands. These compounds inhibited Mycobacterium tuberculosis growth with minimal inhibitory concentrations in the low micromolar range. These data support formation of Mycobacterium tuberculosis G-quadruplexes in vivo and their potential regulation of gene transcription, and prompt the use of G4 ligands to develop original antitubercular agents

Pharmacoutilization of epoetins in na\uc3\uafve patients with hematological malignancies in an unselected italian population under clinical practice setting: A comparative analysis between originator and biosimilars

Aim: The purpose of this study was to assess the prescription of epoetins and consumption of health care resources (in terms of drug treatments) in na\uc3\uafve patients with hematological malignancies in a real-world setting; in particular, we compared the results between reference product and biosimilar products. Methods: An observational retrospective study based on administrative and laboratory databases of three local health units was conducted. All adults diagnosed with hematological malignancies and who had received at least one epoetin (either reference product or biosimilars) prescription for the first time between 1 January 2010 and 30 April 2012 (enrollment period) were included. The date of the first prescription of epoetin within the enrollment period was defined as index date (ID). Patients were followed up for 4 weeks after ID (follow-up period) and were investigated for the 1-year period before the ID. The difference between the last hemoglobin (Hb) measurement after ID and the one prior to ID (\uce\u94Hb) was evaluated. The drug cost analysis was conducted from the perspective of the Italian National Health System. Results: Overall, 69 patients were included in the study; 48 of them received reference epoetin product and 21 received biosimilars as first prescription. Among reference product users, the mean \uc2\ub1 standard deviation (SD) age was 62.5\uc2\ub114.7 years; this cohort of patients was slightly significantly younger than the biosimilar users (71.8\uc2\ub111.8 years). The mean \uc2\ub1SD overall Hb level prior to treatment was lower among patients who started with biosimilar products (9.6\uc2\ub11.1 g/dL) compared to those who started with a reference product (10.1\uc2\ub12.1 g/dL). No significant differences in \uce\u94Hb were observed between biosimilar and originator groups during the followup period. The mean \uef\u82\u81\uef\u81\ubd\uef\u80 SD cost per patient was \ue2\u82\uac667.98\uc2\ub1573.93 and \ue2\u82\uac340.85\uc2\ub1235.73 for the reference product and biosimilar users, respectively (p=0.065). Conclusion: Our study showed that the use of biosimilar products might contribute to controlling health care costs (in terms of drug treatments) for patients with hematological malignancies being maintained by high-quality anemia therapy. Our findings also showed some discordances regarding the most appropriate therapeutic approach in daily clinical practice

Analysis of drug utilization and health care resource consumption in patients with psoriasis and psoriatic arthritis before and after treatment with biological therapies

To describe the therapeutic pathways of patients with psoriasis (PSO) and psoriatic arthritis (PsA) before and after treatment with biological therapies in a real-world setting and to determine the relative consumption of health care resources

An approach to the utilisation of CO2 as impregnating agent in steam pretreatment of sugar cane bagasse and leaves for ethanol production

<p>Abstract</p> <p>Background</p> <p>The conditions for steam pretreatment of sugar cane bagasse and leaves were studied using CO₂as an impregnating agent. The following conditions were investigated: time (5 to 15 min) and temperature (190 to 220°C). The pretreatment was assessed in terms of glucose and xylose yields after enzymatic hydrolysis and inhibitor formation (furfural and hydroxymethylfurfural) in the pretreatment. Results from pretreatment using SO₂as impregnating agent was used as reference.</p> <p>Results</p> <p>For sugar cane bagasse, the highest glucose yield (86.6% of theoretical) was obtained after pretreatment at 205°C for 15 min. For sugar cane leaves the highest glucose yield (97.2% of theoretical) was obtained after pretreatment at 220°C for 5 min. The reference pretreatment, using impregnation with SO₂and performed at 190°C for 5 min, resulted in an overall glucose yield of 79.7% and 91.9% for bagasse and leaves, respectively.</p> <p>Conclusions</p> <p>Comparable pretreatment performance was obtained with CO₂as compared to when SO₂is used, although higher temperature and pressure were needed. The results are encouraging as some characteristics of CO₂are very attractive, such as high availability, low cost, low toxicity, low corrosivity and low occupational risk.</p

Epidemiology, patient profile, and health care resource use for hepatitis C in Italy

The objectives of this study were to estimate the prevalence of Hepatitis C among six Italian Local Health Units (LHUs), to describe patient and antiviral drug characteristics, and to estimate the health care consumption rates and related costs for the management of patients affected by hepatitis C virus (HCV) infection by using data from routine clinical practice

Gilteritinib and the risk of intracranial hemorrhage: a case series of a possible, under-reported side effect

Gilteritinib is currently approved for patients with relapsed/refractory AML with FLT3 mutations, based on the positive results of the pivotal ADMIRAL study. In ADMIRAL trial, no increased risk of bleeding was reported, but in the previous dose finding study, a single event of intracranial hemorrhage (ICH) was registered after exposure to subtherapeutic doses of gilteritinib. Here, we report the first case series on five ICHs diagnosed in patients with FLT3-mutated AML, occurred within the first month of exposure to gilteritinib. Our cohort included 24 patients treated in three Italian centers. Most of these ICH cases were non-severe and self-limiting, while one was fatal. This link with ICHs remains in any case uncertain for the presence of active AML. We further reported that an analysis of the post-marketing surveillance data (EudraVigilance) retrieved other 11 cases of ICHs present in the database after gilteritinib treatment. A causality assessment was performed according to the Dx3 method to evaluate the possibility that ICHs might be an actual side effect of gilteritinib. In conclusion, further research is needed to elucidate the potential role of gilteritinib in the pathogenesis of ICHs

Senhance robotic platform for ovarian borderline tumor treatment: minimally invasive robotic approach for conservative adnexal surgery

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From traumatic childhood to cocaine abuse: the critical function of the immune system

Background: Experiencing traumatic childhood is a risk factor for developing substance use disorder (SUD), but the mechanisms that underlie this relationship have not been determined. Adverse childhood experiences affect the immune system and the immune system mediates the effects of psychostimulants. However, whether this system is involved in the etiology of SUD in individuals who have experience early life stress is unknown. Methods:In this study, we performed a series of ex vivo and in vivo experiments in mice and humans to define the function of the immune system in the early-life stress-induced susceptibility to the neurobehavioral effects of cocaine. Results: We provide evidence that exposure to social-stress (S-S) at an early age permanently sensitizes the peripheral (splenocytes) and brain (microglia) immune responses to cocaine in mice. In the brain, microglial activation in the ventral tegmental area (VTA) of S-S mice was associated with functional alterations in dopaminergic neurotransmission, as measured by whole-cell voltage clamp recordings in dopamine (DA) neurons. Notably, preventing immune activation during the S-S exposure reverted the effects of DA in the VTA and the cocaine-induced behavioral phenotype to control levels. In humans, cocaine modulated Toll-like receptor 4-mediated innate immunity, an effect that was enhanced in cocaine addicts who had experienced a difficult childhood. Conclusions Collectively, our findings demonstrate that sensitization to cocaine in early-life-stressed individuals involves brain and peripheral immune responses and that this mechanism is shared between mice and humans