Prescription patterns of somatostatin analogs in patients with acromegaly and neuroendocrine tumors.

PURPOSE: Acromegaly and neuroendocrine tumors are rare diseases that, under certain conditions, can be treated with somatostatin analogs. The aim was to determine the prescription patterns of somatostatin analogs in a group of patients with acromegaly and neuroendocrine tumors affiliated with the Colombian Health System. METHODS: A retrospective study. A cohort of patients from a drug dispensing database that collected all prescriptions of long-acting somatostatin analogs (octreotide, lanreotide, pasireotide). Sociodemographic variables, clinical variables (diagnosis and comorbidities) and pharmacological therapy variables (dose, changes, persistence of use, comedications) were considered. RESULTS: A total of 213 patients were identified, including 139 (65.3%) with acromegaly and 74 (34.7%) with neuroendocrine tumors. There was a predominance of women (58.7%) and a mean age of 59.7 ± 14.5 years. The most commonly used medications were lanreotide autogel (n = 107; 50.2%), octreotide LAR (n = 102; 47.9%) and pasireotide LAR (n = 4; 1.9%). During follow-up, 11.3% of patients experienced modifications of therapy, with a mean duration from the beginning of treatment to the change in medication of 25 ± 15.9 months. A total of 48.9% of the patients with acromegaly and 87.1% of individuals with neuroendocrine tumors received maximum approved doses of the drug. CONCLUSION: Patients with acromegaly and neuroendocrine tumors in Colombia are mainly women and are most frequently treated with lanreotide autogel for acromegaly and with octreotide LAR for neuroendocrine tumors. In addition, a high proportion are managed with maximum doses of long-acting somatostatin analogs.

A meta-analysis of the effects of colostrum heat treatment on colostral viscosity, immunoglobulin G concentration, and the transfer of passive immunity in newborn dairy calves.

Newborn ruminants depend on colostrum intake immediately after birth to obtain immunoglobulins for effective transfer of passive immunity (TPI). As colostrum may also be a vehicle of infectious agents, heat treatment of raw colostrum is a practice aimed at eliminating or reducing its pathogen load. Despite the usefulness of heat treatment in preventing the transmission of infectious colostrum-borne diseases, heat treatment of colostrum may have some side effects. A systematic review and meta-analysis were conducted to summarize the effects of colostrum heat treatment on colostral viscosity and IgG concentration, and serum IgG concentration as a proxy for TPI in newborn calves fed raw versus heat-treated colostrum. Moderators were studied to identify sources of heterogeneity. Literature databases were searched for peer-reviewed articles published between 1946 and 2022. A Master of Science thesis was also included. Five, 21, and 19 original publications were quantitatively evaluated in 3 separate meta-analyses, based on predefined selection criteria. Two-level and 3-level random-effects meta-analysis revealed a significant overall effect of heat treatment on colostral viscosity and IgG concentration, and serum IgG concentration in newborns. Heat-treated colostrum had significantly higher viscosity (21.0 cP, 95% CI: 3.8 to 38.2) and lower IgG concentration (-7.4 g/L, 95% CI: -11.1 to -3.7) compared with raw colostrum. Overall, newborn calves fed heat-treated colostrum had higher serum IgG concentrations (2.8 g/L, 95% CI: 1.4 to 4.0) 24-48 h after birth than those fed with raw colostrum. Particularly, this positive effect on the serum IgG concentrations was seen when colostrum was heat-treated at ≤60°C (2.9 g/L, 95% CI: 0.9 to 4.2) and when the standard low-temperature low-time (LTLT) method was used for heat treatment (2.6 g/L, 95% CI: 0.1 to 5.1). Colostrum treated at >60-63.5°C tended to have higher viscosity (275.6 cP, 95% CI: -37.9 to 589.3) and had lower IgG concentration (-21.7 g/L, 95% CI: -27.3 to -16.1). Calves fed colostrum treated at this temperature range had significantly lower serum IgG (-4.2 g/L, 95% CI: -7.9 to -0.4) compared with those fed raw colostrum. Heat treatment of colostrum at 72-76°C was not associated with a significant increase in colostral viscosity (6.3 cP, 95% CI: -324.3 to 336.9) nor a reduction in IgG colostral concentration (-13.1 g/L, 95% CI: -26.5 to 0.2), but calves fed colostrum treated at this temperature range had a significant reduction in serum IgG (-11.3 g/L, 95% CI: -17.1 to -5.4). Feeding newborn calves with colostrum heat-treated at ≤60°C by the standard LTLT method, particularly within 2 h after birth, resulted in increased serum IgG concentration at 24-48 h of age. Importantly, delaying feeding of heat-treated colostrum to newborns beyond 2 h of age resulted in no significant difference in IgG serum levels compared with feeding raw colostrum, highlighting the importance of early administration of heat-treated colostrum to favor TPI. On-farm colostrum heat treating should achieve an equilibrium between pathogen elimination and the preservation of colostral immunoglobulins while minimizing undesired increases in viscosity. The beneficial effects of colostrum heat treatment on TPI can be negligible if colostrum feeding is not performed within 2 h after birth.

Including 8 hours of access to alfalfa in 1 or 2 grazing sessions in dairy cows fed a partial mixed ration: Effects on intake, behavior, digestion, and milk production and composition.

The aim of this study was to evaluate the inclusion of alfalfa grazing during 8 h continuous or partitioned in 2 separated sessions of 4 h after each milking, on nutrient intake, digestibility, ruminal fermentation, feeding behavior, milk production, milk composition, and milk fatty acid profile, in late-lactation cows fed a partial mixed ration (PMR). Twelve dairy cows (193 ± 83 d in milk, 584 ± 71 kg of body weight) were housed in individual outdoor pens and assigned to treatments according to a 3 × 3 Latin square design replicated 4 times. The treatments were as follows: (1) control (T0), cows were fed a total mixed ration (TMR) provided ad libitum 20.0% crude protein (CP), 32.2% neutral detergent fiber (NDF); (2) fed a diet combining a PMR which had the same ingredient composition as the TMR (60% of ad libitum intake) + 1 session of 8 h of pasture (T8), continuous grazing alfalfa (Medicago sativa; 20.6% CP, 35.8% NDF) after the p.m. milking; and (3) PMR (60% of ad libitum intake) + 2 daily sessions of 4 h of access to pasture after each milking (T4+4). The experiment lasted 57 d and was divided into 3 periods of 19 d each. The first 12 d of each period was used for diet adaptation, and the last 7 d was used for data collection. No differences among treatments were observed for any of the productive variables, feeding efficiency, or purine derivatives excretion. Cows in T0 had greater intake and apparent digestibility of dry matter, organic matter, and nonfibrous carbohydrates compared with T4+4 and T8. Compared with T0, alfalfa grazing increased the concentration of C18:1 trans-11 and decreased those of C16:0 and C17:0 in milk fat. Cows in T4+4 consumed 1.1 more kg DM/d of alfalfa and N provided by alfalfa in the diet was 3 percentage points higher compared with T8 cows (266 vs. 229 g/d, respectively). In addition, T4+4 cows had a greater daily range of ruminal pH than T8 (0.73 vs. 0.93), and the highest concentrations of NH3-N were recorded during the a.m. grazing session while in T8 cows it occurred during the night. In conclusion, including 8 h of alfalfa grazing in T8 and T4+4 treatments allowed the substitution between 35.8 and 38.7% of the total dry matter intake (DMI) of a PMR (with a similar CP concentration to alfalfa) for pasture, maintaining milk solids production and increasing the C18:1 trans-11 of milk fat compared with a TMR in mid late-lactation cows. In an herbage plus PMR diet, splitting the 1 continuous grazing session of 8 h into 2 sessions of 4 h increased the proportion of energy and N provided by alfalfa pasture and reduced PMR intake, without modifying the total nutrient intake or productive performance of cows.

Silver, copper and copper oxide nanoparticles in the fight against human viruses: progress and perspectives.

The rapid development of nanomedicine has created a high demand for silver, copper and copper oxide nanoparticles. Due to their high reactivity and potent antimicrobial activity, silver and copper-based nanomaterials have been playing an important role in the search for new alternatives for the treatment of several issues of concern, such as pathologies caused by bacteria and viruses. Viral diseases are a significant and constant threat to public health. The most recent example is the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, the object of the present review is to highlight recent progress in the biomedical uses of these metal nanoparticles for the treatment and prevention of human viral infections. We discuss the antiviral activity of AgNPs and Cu-based NPs, including their actions against SARS-CoV-2. We also discuss the toxicity, biodistribution and excretion of AgNPs and CuNPs, along with their uses in medical devices or on inert surfaces to avoid viral dissemination by fomites. The challenges and limitations of the biomedical use of these nanoparticles are presented.

Protective role of lactic acid bacteria and yeasts as dietary carcinogen-binding agents - a review.

The importance of food contaminants in the link between diet and cancer has been widely demonstrated. Therefore, different physical and chemical strategies for the control of human exposure to such dietary carcinogens has been explored; however, most of these strategies are complex, costly, and have low efficiency which limited their applications. Hence, microbiological methods have been receiving more attention. Recent in vitro and in vivo studies have indicated that lactic acid bacteria (LAB) and yeast may act as dietary carcinogen-binding agents. This review describes the promising protective role of strains belonging mainly to the Lactobacillus, Bifidobacterium and Saccharomyces genera by acting as dietary carcinogen-binding agents. This property suggests that these microorganisms may have a protective role by reducing the bioaccessibility of dietary carcinogens, thereby decreasing their toxic effects. The mechanisms by which the binding process takes place have not been completely elucidated; thus, the possible underlying mechanisms and factors influencing carcinogens-binding will be addressed.

Antioxidant capacity and identification of radical scavenging peptides from Crema de Chiapas, Fresco and Cocido cheeses.

Bioactive peptides may positively impact bodily functions. One of these are the antioxidant peptides which are well documented for a wide variety of food matrices, mostly from plant sources. Nevertheless, information of antioxidant milk-derived peptides is still a little-known field. The present study was aimed to evaluating the antioxidant capacity (AC) in vitro of water soluble extracts < 3 kDa (WSE) from three artisanal Mexican cheeses: Crema de Chiapas (CrC), Fresco (FC) and Cocido (CC). This study was carried out for cheeses of different days of storage (0, 5, 10, 15, and 20) at 4 °C. AC was assayed to the respective WSE by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diamoniun salt (ABTS) and oxygen radical absorbance capacity (ORAC) methods and those WSE that showed the most antioxidant capacity from each cheese were analyzed by using RP-HPLC/MS to identify and characterize the novel specific peptides. All the WSE analyzed show antioxidant capacity, especially those from CrC and CC which display the highest AC at 15 days of storage. Regarding to WSE from FC, the AC was constant during storage. Identified structures reveal that these novel peptides possess high content of specific amino acids, mainly proline, valine, leucine and phenylalanine, of which it has already been shown antioxidant properties. This study demonstrate that these artisanal Mexican cheeses are sources of potential antioxidant peptides.

Drought impact on forest carbon dynamics and fluxes in Amazonia.

In 2005 and 2010 the Amazon basin experienced two strong droughts, driven by shifts in the tropical hydrological regime possibly associated with global climate change, as predicted by some global models. Tree mortality increased after the 2005 drought, and regional atmospheric inversion modelling showed basin-wide decreases in CO2 uptake in 2010 compared with 2011 (ref. 5). But the response of tropical forest carbon cycling to these droughts is not fully understood and there has been no detailed multi-site investigation in situ. Here we use several years of data from a network of thirteen 1-ha forest plots spread throughout South America, where each component of net primary production (NPP), autotrophic respiration and heterotrophic respiration is measured separately, to develop a better mechanistic understanding of the impact of the 2010 drought on the Amazon forest. We find that total NPP remained constant throughout the drought. However, towards the end of the drought, autotrophic respiration, especially in roots and stems, declined significantly compared with measurements in 2009 made in the absence of drought, with extended decreases in autotrophic respiration in the three driest plots. In the year after the drought, total NPP remained constant but the allocation of carbon shifted towards canopy NPP and away from fine-root NPP. Both leaf-level and plot-level measurements indicate that severe drought suppresses photosynthesis. Scaling these measurements to the entire Amazon basin with rainfall data, we estimate that drought suppressed Amazon-wide photosynthesis in 2010 by 0.38 petagrams of carbon (0.23-0.53 petagrams of carbon). Overall, we find that during this drought, instead of reducing total NPP, trees prioritized growth by reducing autotrophic respiration that was unrelated to growth. This suggests that trees decrease investment in tissue maintenance and defence, in line with eco-evolutionary theories that trees are competitively disadvantaged in the absence of growth. We propose that weakened maintenance and defence investment may, in turn, cause the increase in post-drought tree mortality observed at our plots.

Long-term decline of the Amazon carbon sink.

Atmospheric carbon dioxide records indicate that the land surface has acted as a strong global carbon sink over recent decades, with a substantial fraction of this sink probably located in the tropics, particularly in the Amazon. Nevertheless, it is unclear how the terrestrial carbon sink will evolve as climate and atmospheric composition continue to change. Here we analyse the historical evolution of the biomass dynamics of the Amazon rainforest over three decades using a distributed network of 321 plots. While this analysis confirms that Amazon forests have acted as a long-term net biomass sink, we find a long-term decreasing trend of carbon accumulation. Rates of net increase in above-ground biomass declined by one-third during the past decade compared to the 1990s. This is a consequence of growth rate increases levelling off recently, while biomass mortality persistently increased throughout, leading to a shortening of carbon residence times. Potential drivers for the mortality increase include greater climate variability, and feedbacks of faster growth on mortality, resulting in shortened tree longevity. The observed decline of the Amazon sink diverges markedly from the recent increase in terrestrial carbon uptake at the global scale, and is contrary to expectations based on models.

Histidine Self-assembly and Stability on Mineral Surfaces as a Model of Prebiotic Chemical Evolution: An Experimental and Computational Approach.

The abiotic synthesis of histidine under experimental prebiotic conditions has proven to be chemically promising and plausible. Within this context, the present results suggest that histidine amino acid may function as a simple prebiotic catalyst able to enhance amino acid polymerization. This work describes an experimental and computational approach to the self-assembly and stabilization of DL-histidine on mineral surfaces using antigorite ((Mg, Fe)3Si2O5(OH)4), pyrite (FeS2), and aragonite (CaCO3) as representative minerals of prebiotic scenarios, such as meteorites, and subaerial and submarine hydrothermal systems. Experimental results were obtained through polarized-light microscopy, IR spectroscopy (ATR-FTIR), and differential scanning calorimetry (DSC). Molecular dynamics was performed through computational simulations with the MM + method in HyperChem software. IR spectra suggest the presence of peptide bonds in the antigorite-histidine and aragonite-histidine assemblages with the presence of amide I and amide II vibration bands. The FTIR second derivative inspection supports this observation. Moreover, DSC data shows histidine stabilization in the presence of antigorite and aragonite by changes in histidine thermodynamic properties, particularly an increase in histidine decomposition temperature (272ºC in antigorite and 275ºC in aragonite). Results from molecular dynamics are consistent with DSC data, suggesting an antigorite-histidine closer interaction with decreased molecular distances (cca. 5.5 Å) between the amino acid and the crystal surface. On the whole, the experimental and computational outcomes support the role of mineral surfaces in prebiotic chemical evolution as enhancers of organic stability.

Intensification strategies for temperate hot-summer grazing dairy systems in South America: Effects of feeding strategy and cow genotype.

Pasture-based dairy systems present the opportunity to increase productivity per hectare through increasing stocking rate and forage utilization. However, in the temperate hot-summer region of South America, different productive strategies are being adopted by farmers. The aim of this study was to quantify the effect of feeding strategy (FS) and cow genotype (G) on individual animal and whole-farm biophysical performance. A design with 2 × 2 levels of intensification aiming to increase home-grown forage utilization and milk output per hectare was evaluated. The experiment was a randomized complete block design with a 2 × 2 factorial arrangement of treatments, combining 2 feeding strategies with varying proportions of grazing in the annual feeding budget [grass fixed (GFix) and grass maximum (GMax)] and 2 Holstein Friesian cow genotypes [New Zealand (NZHF) or North American Holstein Friesian (NAHF)]. The effects of FS, G, and their interaction were analyzed using mixed models. New Zealand Holstein Friesian cows presented lower individual milk yield and higher milk component concentrations, maintained higher average body condition score, and increased body weight (BW) throughout the experiment, while presenting a better reproductive performance compared with the NAHF cows. Although all farmlets were planned at the same stocking rate on a per kilogram of BW basis, the current stocking rate changed as a result of animal performance and grass utilization resulting in NZHF cows achieving greater BW per hectare. The superior stocking rate led to greater milk solids production and feed consumption per hectare for the systems with NZHF cows. The GFix feeding strategy resulted in greater total home-grown forage harvest and conserved forage surplus than GMax. Overall, it was feasible to increase stocking rate and increase milk production per hectare from home-grown forage with differing feeding strategies and Holstein Friesian cow genotypes within grazing systems located in the temperate hot-summer climate region of South America. The interactions reported between FS × G highlight the superior productivity per hectare of NZHF cows within the GMax feeding strategy based on maximizing grazed pasture, which could represent a competitive intensification strategy in terms of cost of production for this region.

Immunohistochemical localization of TNF-α and IL-4 in granulomas of immunocompetent and immunosuppressed New Zealand white rabbits infected with Encephalitozoon cuniculi.

Encephalitozoon cuniculi is a fungi-related, obligate, zoonotic, spore-forming intracellular eukaryotic microorganism. This emerging pathogen causes granulomas to form in the brain and kidneys of infected individuals. The objective of the current study was to detect the distribution of TNF-α- and IL-4-positive cells using immunohistochemistry within these granulomas in both infected immunocompetent (group A) and immunosuppressed (group B) New Zealand white rabbits. In the brain, labeled TNF-α immune cells were mainly located in the granuloma peripheries in group B. Granulomas examined in the kidneys of groups A and B were TNF-α positive, but were significantly different (p < 0.001) when compared with the brain. IL-4-producing immune cells in the brain and kidneys were disseminated within granulomas in groups A and B; however, no significant difference (p > 0.05), was observed. IL-4 positive cells were more numerous in brain sections of group B and differed significantly (p < 0.05) when compared with kidneys. Granulomas were not observed in control animals (groups C and D). In conclusion, we identified TNF-α positive cells in both the brain and kidneys of immunocompetent and immunosuppressed animals; IL-4 positive cells were numerous in the brains of immunosuppressed rabbits; however, in terms of percentage were numerous in the brains of immunocompetent rabbits. Immunosuppression appeared to stimulate a change in the cellular phenotype of Th1- to Th2-like granulomas in the brain and kidneys via an unknown mechanism. Expression of pro- and pre-inflammatory cytokines in microsporidian granulomas suggests a mechanism by which E. cuniculi evades the immune response, causing more severe disease. These results increase our understanding of TNF-α and IL-4-positive cells within the E. cuniculi granuloma microenvironment.

Clofibrate improves myocardial ischemia-induced damage through regulation of renin-angiotensin system and favours a pro-vasodilator profile in left ventricle.

Myocardial ischemia initiates a chain of pathological conditions leading to cardiomyocyte death. Therefore, pharmacological treatment to stop ischemia-induced damage is necessary. Fibrates, have been reported to decrease inflammatory markers and to modulate the renin-angiotensin system (RAS). Our aim was to explore if clofibrate treatment, administered one week after myocardial event, decreases MI-induced cardiac damage. Wistar rats were assigned to: 1. Sham or 2. Coronary artery ligation (MI). Seven days after, rats were subdivided to receive vehicle (V) or clofibrate [100 mg/kg (C)] daily for 7 days. Blood samples and left ventricle were analyzed. RAS components [angiotensin II, angiotensin converting enzyme (ACE), and AT1-receptor] decreased in MI-C compared to MI-V, while [Ang-(1-7), bradykinin, ACE-2, and AT2-receptor] raised in response to clofibrate treatment. Oxidative stress markers increased in MI-V rats, a profile reverted in MI-C rats. Nitric oxide (NO) pathway (Akt, eNOS, and NO) exhibits a lower participation in MI-V, but clofibrate raised NO-pathway components and its production. MI-induced fibrosis and structural damage was also improved by clofibrate-treatment. In conclusion, clofibrate administration to 7 days MI-rats exerts an antioxidant, pro-vasodilator expression profile, and anti-fibrotic effect suggesting that PPARα activation can be considered a therapeutic target to improve cardiac condition posterior to ischemia.

Tempo and mode in coevolution of Agave sensu lato (Agavoideae, Asparagaceae) and its bat pollinators, Glossophaginae (Phyllostomidae).

The genus Agave sensu lato contains ca. 211 described species, many of which are considered keystone species because of their ecological dominance and the quantity of resources they provide with their massive, nectar-rich inflorescences. The large diversity of Agave species has been hypothesized as being related to their reproductive strategy (predominantly monocarpic) and diverse pollinators (e.g., bats, hummingbirds, hawkmoths). In particular, Agave species provide resources that a few genera of nectar feeding bats from the subfamily Glosophaginae are dependent upon. To explore a possible coevolutionary relationship between Agave and the bat species that pollinate them, we calibrated molecular phylogenies of both groups and looked for a correlation in their dates of divergence. One coding and two non-coding regions of the chloroplast genome were sequenced from 49 species of the Agavoideae (Asparagaceae), and the mitochondrial gene Cyt-b and nuclear coding gene RAG2 were either sequenced or obtained from gene bank for 120 Phyllostomid bats. Results from the analyses indicate that Agave sensu lato is a young genus (estimated crown age 2.7-8.5/stem age 4.6-12.3 Ma), with an increasing diversification rate, and the highest speciation rate among Agavoideae's clades. The origin of the Glossophaginae bats (stem age 20.3-23.5 Ma) occurred prior to the stem age of Agave sensu lato, while the origin of the current pollinators of Agave species, members of the genera Glossophaga, Leptonycteris, Anoura, Choeronyscus, Musonycteris and Choeronycteris, was estimated to be around 6.3-16.2 Ma, overlapping with the stem age of Agave sensu lato, supporting the hypothesis of diffuse coevolution.

Striatal Protection in nNOS Knock-Out Mice After Quinolinic Acid-Induced Oxidative Damage.

Under pathological conditions, nitric oxide can become a mediator of oxidative cellular damage, generating an unbalance between oxidant and antioxidant systems. The participation of neuronal nitric oxide synthase (nNOS) in the neurodegeneration mechanism has been reported; the activation of N-methyl-D-aspartate (NMDA) receptors by agonist quinolinic acid (QUIN) triggers an increase in nNOS function and promotes oxidative stress. The aim of the present work was to elucidate the participation of nNOS in QUIN-induced oxidative stress in knock-out mice (nNOS-/-). To do so, we microinjected saline solution or QUIN in the striatum of wild-type (nNOS +/+), heterozygote (nNOS+/-), and knock-out (nNOS-/-) mice, and measured circling behavior, GABA content levels, oxidative stress, and NOS expression and activity. We found that the absence of nNOS provides a protection against striatal oxidative damage induced by QUIN, resulting in decreased circling behavior, oxidative stress, and a partial protection reflected in GABA depletion. We have shown that nNOS-derived NO is involved in neurological damage induced by oxidative stress in a QUIN-excitotoxic model.

Productive performance and digestive response of dairy cows fed different diets combining a total mixed ration and fresh forage.

The purpose of this experiment was to determine the effects of feeding increasing levels of fresh forage (FF) as a proportion of total dry matter intake (DMI) on nutrient intake, rumen digestion, nutrient utilization, and productive performance of total mixed ration (TMR)-fed cows. Twelve dairy cows (90 ± 22 d in milk, 523 ± 88 kg of body weight, 7,908 ± 719 kg of milk production in the previous lactation) were housed in individual tiestalls and assigned to treatments according to a 3 × 3 Latin square design replicated 4 times. Treatments were 100% TMR (T100), 75% TMR plus 25% FF (T75), and 50% TMR plus 50% FF (T50). The experiment lasted 60 d, divided into 3 periods of 20 d each; the first 12 d of each period were used for diet adaptation and the last 8 d for data collection. The TMR (18.1% crude protein, 24.6% acid detergent fiber) and FF (Lolium multiflorum; 15.1% crude protein, 24.1% acid detergent fiber) were prepared and cut daily and offered to each cow individually. The highest DMI was reached in T100 and T75, which was reflected in greater intake of the different nutrients than T50. No differences were detected in the apparent total digestibility of the nutrients, mean ruminal pH, and total volatile fatty acid concentrations among treatments. Cows in T50 resulted in the lowest ruminal N-NH3 concentration and the lowest microbial N flow to the duodenum. Milk yield was 8.5% higher from cows in T100 and T75 compared with T50, but we observed no differences for milk fat or milk protein yield among treatments. Milk fat of cows fed T50 had 8% more unsaturated fatty acids (FA) than that of cows fed T100, mostly because of a higher content of monounsaturated FA. Additionally, cows in T50 had a higher concentration of linoleic acid, vaccenic acid, and rumenic acid than T100. Meanwhile, the concentration of linoleic acid and vaccenic acid in cows fed T75 was higher than T100. The milk fat of the cows fed T50 and T75 had a lower n-6:n-3 ratio than T100. We concluded that including up to 29% of FF in the total DMI in combination with a TMR did not affect the intake or digestion of nutrients or the productive response in dairy cows and resulted in a higher concentration of desirable FA from a consumer's perspective.

Reducing milking frequency in early lactation improved the energy status but reduced milk yield during the whole lactation of primiparous Holstein cows consuming a total mixed ration and pasture.

To investigate the immediate and long-term performance effects of milking frequency during early lactation of primiparous dairy cows consuming a total mixed ration and pasture, 20 Holstein cows were assigned in a randomized block design to either once-daily (1×) or twice-daily (2×) milking during the first 8 wk of lactation (treatment period). After the treatment period, all cows were milked 2× until wk 43 of lactation. Cows were fed a total mixed ration (approximately 15 kg of DM/cow per day) and allowed to graze an oat pasture (Avena sativa). Dry matter intake was 19.1 kg of DM/cow per day on average and was not affected by treatments. Milk yield was 40% lower in cows milked 1× during the treatment period, and a carryover effect existed until wk 21 of lactation, resulting in a final reduction of 15% of milk yield in the whole lactation. Milk lactose concentration decreased, whereas fat and protein concentrations increased for cows milked 1×. Mobilization of energy reserves during the treatment period occurred in both groups, but cows milked 1× showed greater body condition score and greater backfat thickness. In conclusion, milking 1× during the first 8 wk of lactation resulted in immediate and carryover negative effects on milk and milk solid yield without affecting feed intake, resulting in the improved energy status of primiparous dairy cows.

Forensic parameters and admixture in Mestizos from five geographic regions of Mexico based on 20 autosomal STRs (Powerplex 21 system).

We analyzed Mestizo (admixed) population samples from different geographic regions of Mexico (n = 1283) with 20 autosomal STRs (PowerPlex® 21, Promega Corp.). Allele frequencies and forensic parameters from the Northwest, Northeast, West, Center, and Southeast regions are reported, as well as from the pooled Mexican population sample. The combined PD and PE for this 20 STR system were > 0.9999999999 and > 0.99999996593% in all five population samples, respectively. Analysis of molecular variance (AMOVA) of these Mexican population samples, plus Monterrey (Northeast) and Mexico (Center) Cities, showed low but significant differences among Mexican-Mestizos from the seven populations (Fst = 0.20%; p = 0.0000). Structure analysis showed the highest proportion of Native American ancestry in Mexico City, Center, and Southeast regions, respectively, which was in agreement with the estimated genetic distances represented in a MDS plot and a NJ tree. The best fit of population clusters (K = 4) obtained with the Structure software indicates that Mexican-Mestizos are mainly composed by European, African, and two Native American ancestries. The European and Native American ancestries displayed a contrary gradient, increasing toward the North-West and South-Southeast, respectively. These 20 autosomal STR loci improved the admixture estimation regarding previous studies with the 13 CODIS-STRs, as supported by the higher similarity with previous estimates based on genome-wide SNP. In brief, this study validates the confident use of the PowerPlex® 21 system for human identification purposes in Mestizo populations throughout the Mexican territory.

Generalized pustular psoriasis triggered by Zika virus infection.

Zika virus is an emerging arbovirus, which is expanding in epidemic proportions through tropical and subtropical areas of the world. Although Zika is linked to a number of congenital and neurological complications, there is scarce knowledge on the impact of ZIKV infection in human skin. We report the case of a 68-year old woman who presented with generalized pustular psoriasis after a preceding and otherwise uneventful episode of ZIKV infection. Based on recent experimental data on the biology of ZIKV infection in the cutaneous environment, we speculate that ZIKV may have directly triggered the development of generalized pustular psoriasis by stimulation of keratinocyte-derived mediators of inflammation and a polyfunctional T-cell driven immune reaction in the cutaneous milieu.

Correspondence between the CYP2C19 and CYP3A4 genotypes with the inferred metabolizer phenotype by omeprazole administration in Mexican healthy children.

WHAT IS KNOWN AND OBJECTIVE: CYP2C19 genotypes presumably allow the prediction of the metabolizer phenotypes: poor (PMs), extensive (EMs) and ultra-rapid (UMs). However, evidence from previous studies regarding this predictive power is unclear, which is important because the benefits expected by healthcare institutions and patients are based on this premise. Therefore, we aimed to complete a formal evaluation of the diagnostic value of CYP2C19 and CYP3A4 genes for predicting metabolizer phenotypes established by omeprazole (OME) administration in 118 healthy children from Jalisco (western Mexico). METHODS: The genotypes for CYP3A4*1B and CYP2C19*2, *3, *4, *5 and *17 alleles were determined. CYP2C19 and CYP3A4 phenotypes were obtained after 20 mg OME administration and HPLC quantification in plasma to estimate the Hydroxylation Index (HI = OME/HOME) and Sulfonation Index (SI = OME/SOME), respectively. RESULTS AND DISCUSSION: The distribution of genotypes and phenotypes for CYP2C19 and CYP3A4 was similar to previous studies in Mexico and Latin America. We estimated the CYP2C19 UM, EM and PM phenotype frequency in 0.84%, 96.61% and 2.54%, respectively. Although differences in the HI distribution were observed between CYP2C19 genotypes, they showed a poor diagnostic ability to predict the CYP2C19 metabolizer phenotype. Similarly, the number of CYP2C19 and CYP3A4 functional alleles was correlated with the HI distribution, but also their diagnostic ability to predict the CYP2C19 phenotype was poor. WHAT IS NEW AND CONCLUSION: The CYP2C19 phenotype is not predicted by the number of functional alleles of CYP2C19 and CYP3A4 genes. Phenotyping is still the most valuable alternative to dose individualization for CYP2C19 substrate drugs.

The role of the IL-8 signaling pathway in the infiltration of granulocytes into the livers of patients with alcoholic hepatitis.

BACKGROUND AND AIM: IL-8 (C-X-L motif chemokine ligase 8) and CXCR2 (C-X-C-motif chemokine receptor 2) are up regulated in alcoholic hepatitis (AH) liver biopsies. One of the consequences is the attraction and chemotactic neutrophilic infiltrate seen at the AH stage of alcoholic liver disease. MATERIALS AND METHODS: Human formalin-fixed, paraffin-embedded (FFPE) liver biopsies from patients who have AH were studied by (2.1) RNA sequencing, (2.2) PCR and (2.3) semi quantitation of specific proteins in biopsy sections using immunohistochemical measurements of antibody fluorescent intensity with morphometric technology. RESULTS: Immunohistochemistry of IL-8 showed that the expression was increased in the cytoplasm of the hepatocytes in AH liver biopsies compared to the controls. IL-8 and ubiquitin were co-localized in the MDBs. Numerous neutrophils were found throughout and satellitosis of neutrophils around MDBs was present. This suggested that IL-8 may be involved in MDB pathogenesis. RNA seq analysis revealed activation by IL-8 which included neutrophil chemotaxis by LIM domain kinase 2 (LIMK2) (17.5 fold increase) and G protein subunit alpha 15 (GNA15) (27.8 fold increase). CONCLUSIONS: The formation of MDBs by liver cells showed colocalization of ubiquitin and IL-8 in the MDBs. This suggested that IL-8 in these hepatocytes attracted the neutrophils to form satellitosis. This correlated with up regulation of the proteins downstream from the IL-8 pathways including LIMK2, GNG2 (guanine nucleotide binding proteins) and PIK3CB (phosphatidyl isitol-4, 5-biophosphate-3-kinase, catalytic subunit beta).