Potential use of HSP70 as an indicator of heat stress in dairy cows - a review.

Heat stress (HS) poses significant challenges to the dairy industry, resulting in reduced milk production, impaired reproductive performance, and compromised animal welfare. Therefore, understanding the molecular mechanisms underlying cellular responses to HS is crucial for developing effective strategies to mitigate its adverse effects. Heat shock protein 70 (HSP70) has emerged as a potential player involved in cellular thermotolerance in dairy cows. This review provides a comprehensive overview of the role of HSP70 as a molecular chaperone in cellular thermotolerance in dairy cows under HS. HSP70 facilitates proper protein folding and prevents the aggregation of denatured proteins. By binding to misfolded proteins, it helps maintain protein homeostasis and prevents the accumulation of damaged proteins during HS. Additionally, HSP70 interacts with various regulatory proteins and signaling pathways, contributing to the cellular adaptive response to HS. The upregulation of HSP70 expression in response to HS is regulated by a complex network involving heat-shock factors (HSFs), heat-shock element-binding proteins, and HSF co-chaperones. Therefore, HSP70 holds the potential to be a useful indicator of tissue stress due to its role in maintaining cellular balance, and as it is released both inside and outside cells in response to stress. Traditional methods of measuring HSP70 in blood samples are labor-intensive, and with the process being potentially stressful for the animals and may subsequently affect the results. Therefore, measuring HSP expression in cow's milk has shown promise as an easy, non-invasive, and accurate way to detect HS in dairy cows. Monitoring HSP70 levels in milk can be applied as a supplementary approach to identify HS or HS resistance of individual cows, selection of suitable animals and to guide targeted management strategies. However, despite the potential advantages of using HSP70 as a biomarker for monitoring HS on dairy cows, challenges remain in standardizing measurement protocols, establishing species-specific reference ranges, addressing inter-individual variations, and determining the specificity of changes in HSP70 due to HS. Future research should focus on developing non-invasive techniques for HSP70 detection, with consideration of climatic conditions, and unravelling the molecular interactions and regulatory networks involving HSP70.

A different perspective on sofosbuvir-ledipasvir treatment of patients with HCV genotype 1b cirrhosis: The ital-c network study.

The effectiveness of a 12-week course of sofosbuvir-ledipasvir in treatment-experienced HCV genotype 1b-infected patients with cirrhosis is still under debate. Our primary endpoint was to compare the sustained virological response at post-treatment week 12 (SVR12) of sofosbuvir-ledipasvir in combination with ribavirin for 12 weeks, and sofosbuvir-ledipasvir alone for 24 weeks. This was a prospective observational study that enrolled 424 (195 naive, 229 experienced; 164 treated for 12 weeks with Ribavirin and 260 with sofosbuvir-ledipasvir alone for 24 weeks) consecutive HCV genotype 1b-infected patients with cirrhosis. The SVR12 rates were 93.9% and 99.2% in patients treated for 12 and 24 weeks, respectively (P = .002). The baseline characteristics of patients treated for 12 weeks were significantly different from those treated for 24 weeks as regards their younger age (P = .002), prevalence of Child-Pugh class A (P = .002), lower MELD scores (P = .001) and smaller number of nonresponders (P = .04). The shorter treatment was significantly associated with a lower SVR12 in univariate and multivariate analyses (P = .007 and P = .008, respectively). The SVR rate was unaffected by age, gender, BMI, Child-Pugh class, MELD score or previous antiviral treatment. Patients receiving ribavirin experienced more episodes of ascites and headache but less recurrence of hepatocellular carcinoma (HCC), and were prescribed more diuretics and cardiopulmonary drugs. No patient discontinued treatment. The therapeutic regimen of sofosbuvir-ledipasvir plus ribavirin administered for 12 weeks was less effective than sofosbuvir-ledipasvir alone given for 24 weeks. At odds with European guidelines, the recommended 12-week treatment with sofosbuvir-ledipasvir alone might be suboptimal for this setting of patients.

Tolerability and efficacy of anti-HBV nucleos(t)ide analogues in HBV-DNA-positive cirrhotic patients with HBV/HCV dual infection.

We evaluated tolerability and virological and clinical impact of anti-Hepatitis B Virus (HBV) nucleos(t)ide analogues in cirrhotic patients with HBV/Hepatitis C Virus (HCV) coinfection. The virological and clinical course of 24 consecutive HBsAg/HBV-DNA/anti-HCV-positive patients with cirrhosis was compared with that of 24 HBsAg/HBV-DNA-positive, anti-HCV-negative cirrhotic patients, pair-matched for age (±5 years), sex, HBeAg/anti-HBe status and Child-Pugh class. Patients in both groups were previously untreated with oral antiviral agents at enrollment and were treated for at least 24 months (range 24-54). At the 12th and 18th month of treatment, HBV-DNA was negative in 21 (87.5%) and 23 (95.8%) patients with hepatitis B and C and in 20 (83.3%) and 22 (91.6%) in patients with isolated HBV; all patients in both groups were HBV-DNA-negative at month 24 and at subsequent observations. Treatment was well tolerated by all patients in both groups. At the last observation (for co-infected patients, median 44 months and range 24-54; for mono-infected patients, median 40 months and range 24-54), a deterioration in Child class was observed in eight (47%) of 17 patients in patients with both HBV and HCV who were HCV-RNA-positive at baseline, but in none of seven HCV-RNA-negative patients in the same group, and in one patient (4.2%) in the mono-infected patients. Reactivation of HCV infection was relatively infrequent (12.5% of cases) and never associated with a clinical deterioration. Treatment with nucleotides in HBsAg/HBV-DNA/anti-HCV-positive patients with cirrhosis showed a favourable virological effect in all cases, but a favourable clinical result only in the HCV-RNA-negative at baseline.

Factors affecting the changes in molecular epidemiology of acute hepatitis B in a Southern Italian area.

To explore changes in molecular epidemiology of acute viral hepatitis B (AVH-B), hepatitis B virus (HBV) genotypes were determined by direct sequencing of the Pre-S-S region in 123 consecutive patients, with AVH-B observed in Naples or its surroundings in the last decade (group AVH-B) and in 123 HBV chronic carriers [chronic carrier of HBV (CC-B) group] from the same areas, who had been hepatitis B surface antigen-positive for more than 10 years. Genotype D was less frequently detected in patients with AVH-B than in those in the CC-B group (76.4%vs 97.5%, P < 0.0001). In the AVH-B group, intravenous drug addiction (IVDA) was the prevalent risk factor (55.3%) for acquiring HBV in the 94 patients with HBV genotype D, but it was rarely recorded (6.9%) in the 29 patients with genotypes non-D (P < 0.0001); unsafe sexual intercourse was prevalent in patients with genotype non-D (72.3%) and less frequent in those with genotype D (28.8%, P < 0.005). In the AVH-B group, the prevalence of non-D genotypes increased during the observation period from 11.1% in 1999-2003 to 41.1% in 2004-2008 (P < 0.0005), paralleling the increase in the prevalence of patients with unsafe sexual intercourse; similarly, the progressive decrease in IVDA paralleled the decrease in the prevalence of genotype D (from 88.3% in 1999-2003 to 11.7% in 2004-2008). The prevalence of HBV non-D genotypes recorded in the last 10 years in AVH-B in this area shows a progressive increase, most probably because of recent changes in HBV epidemiology, namely, the HBV mass vaccination campaign and increased immigration from areas with high HBV endemicity.

Virological patterns of hepatitis C virus patients with failure to the current-generation direct-acting antivirals.

There are few data on the virological characterisation of patients with failure to current-generation direct-acting antivirals (DAAs), namely elbasvir/grazoprevir, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir. This study aimed to characterise virological patterns in patients with failure to current DAA regimens as well as the efficacy of re-treatment. All 61 consecutive hepatitis C virus (HCV) treatment-naïve patients with failure to current DAAs from January 2018 to February 2019 were enrolled. Sanger sequencing of NS3, NS5A and NS5B proteins was performed using homemade protocols. NS5A resistance-associated substitutions (RASs) were more frequent in the 17 patients treated with sofosbuvir/velpatasvir (89.5%) and 33 patients treated with elbasvir/grazoprevir (97%) compared with the 11 patients treated with glecaprevir/pibrentasvir (18.2%) (P = 0.002 and 0.000, respectively). NS3 RASs were more often detected in the 33 patients with failure to elbasvir/grazoprevir (30.3%) than in the 11 patients treated with glecaprevir/pibrentasvir (9.1%). NS3 RASs were also detected in 12% of sofosbuvir/velpatasvir-treated patients. NS5B RASs were infrequently identified. Of the glecaprevir/pibrentasvir-treated patients, 73% did not show RASs in any HCV regions, a prevalence higher than that observed in those treated with elbasvir/grazoprevir (0%; P < 0.05) or sofosbuvir/velpatasvir (12%; P < 0.05). Of the 61 patients, 21 (34.4%) were re-treated with sofosbuvir/velpatasvir and voxilaprevir. All patients achieved sustained virological response at 12 weeks (SVR12). To our knowledge, this is one of the first real-life studies describing patients who failed current-generation DAAs; the prevalence of RASs differed according to the DAA regimen used, and the efficacy of re-treatment was high.

Negative impact of hyperglycaemia on tocilizumab therapy in Covid-19 patients.

Tocilizumab (TCZ) is used for treating moderate-to-severe Covid-19 pneumonia by targeting interleukin-6 receptors (IL-6Rs) and reducing cytokine release. Yet, in spite of this therapy, patients with vs. patients without diabetes have an adverse disease course. In fact, glucose homoeostasis has influenced the outcomes of diabetes patients with infectious diseases. Of the 475 Covid-19-positive patients admitted to infectious disease departments (University of Bologna, University Vanvitelli of Napoli, San Sebastiano Caserta Hospital) in Italy since 1 March 2020, 31 (39.7%) hyperglycaemic and 47 (60.3%) normoglycaemic patients (blood glucose levels ≥140mg/dL) were retrospectively evaluated at admission and during their hospital stay. Of note, 20 (64%) hyperglycaemic and 11 (23.4%) normoglycaemic patients had diabetes (P<0.01). At admission, hyperglycaemic vs. normoglycaemic patients had fivefold higher IL-6 levels, which persisted even after TCZ administration (P<0.05). Intriguingly, in a risk-adjusted Cox regression analysis, TCZ in hyperglycaemic patients failed to attenuate risk of severe outcomes as it did in normoglycaemic patients (P<0.009). Also, in hyperglycaemic patients, higher IL-6 plasma levels reduced the effects of TCZ, while adding IL-6 levels to the Cox regression model led to loss of significance (P<0.07) of its effects. Moreover, there was evidence that optimal Covid-19 infection management with TCZ is not achieved during hyperglycaemia in both diabetic and non-diabetic patients. These data may be of interest to currently ongoing clinical trials of TCZ effects in Covid-19 patients and of optimal control of glycaemia in this patient subset.

Evaluation of different bovine muscles to be applied in freeze-drying for instant meal. Study of physicochemical and senescence parameters.

The aim of the present research was to evaluate bovine muscles to be subjected to freeze-drying for an instant meal. Physicochemical and senescence parameters were evaluated. The experimental part was divided into two steps. In the first step, the Semitendinosus muscle was chosen to establish methodology and experimental conditions. Physicochemical, microstructure and senescence parameters were analysed. In the second step, economic bovine muscles such as Semimembranous and Spinalis dorsi were subjected to the same methodology and conditions as in the first step in order to compare them by analysing the same parameters. L* and a* values were statistically significant (P<0.05) for Semimembranous and Spinalis dorsi muscles, showing differences among condition effects and in muscles. Humidity and water activity showed among the muscles analysed that cooked and rehydrated samples did not exhibit differences. Microstructure of Semitendinosus and Semimembranous were not separated and fragmented as occurred with Spinalis dorsi after freeze-drying. Results allowed us to select among the muscles studied that Semimembranous was suitable and economic to be used in an instant meal.

Non responders to interferon therapy among chronic hepatitis patients infected with hepatitis C virus.

We studied a series of 268 chronic hepatitis C patients (31 chronic persistent hepatitis CPH, 69 mild chronic active hepatitis CAH, 125 severe CAH, and 43 active cirrhosis) enrolled from 1988 to 1991 in different therapeutic protocols using lymphoblastoid or recombinant interferon (IFN) at a dosage of 3 mega units (M.U.), three times a week for 12 months. Of these patients 54.8% showed a complete response (normalization of aminotransferases), 14.2% a partial response (decrease in aminotransferases of over 50%), 27.6% no response, and 3.4% a substantial progressive increase in the liver enzymes during IFN (becoming worse). The prevalence of non responders was lower in CPH (9.7%) than in CAH patients (31.9% in the mild form and 20.8% in the severe), and significantly higher in patients with cirrhosis (53.5%). No correlation was observed between non response and the baseline aminotransferase level or the patient's sex. Patients under 35 had a better response to IFN when compared with patients 36-50 years. This is probably due to the higher prevalence of CPH patients with a good response to IFN in the youngest group. No effect was gained in non responders by increasing the dose or shifting from recombinant to lymphoblastoid IFN; three patients were then treated with steroids, but only one benefitted. For 5 of the 9 patients who became worse, steroids were started after discontinuation of IFN therapy, and they induced a favorable response only for the 3 who had developed autoantibodies during IFN treatment.

Variations of prolactin content in human cerebrospinal fluid after metoclopramide and morphine.

Serum and cerebrospinal fluid (CSF) prolactin (PRL) concentrations were determined in fourteen patients of both sexes suffering from hydrocephalus, in basal conditions and after i.m. administration of 10 mg metoclopramide or 10 mg morphine. A significant increase in both serum and CSF hormone values was found after administration of both drugs. Serum and CSF PRL values after metoclopramide administration increased earlier and to a greater extent than after morphine. Furthermore, the metoclopramide induced CSF PRL increase immediately followed the serum peak, whereas after morphine administration an evident delay in the CSF hormone peak with respect to the serum increase was found. These data suggest that PRL entry in the CSF compartment is subject to a controlling mechanism which acts at the blood/brain barrier.

Diurnal beta-endorphin changes in human cerebrospinal fluid.

Plasma and cerebrospinal fluid (CSF) beta-endorphin levels were determined by a RIA method in seven hydrocephalic male patients. The samples were simultaneously collected every two hours from 8 AM to 12 midnight and every hour from 1 AM to 7 AM. In both plasma and CSF beta-endorphin levels showed significant time-related variations during the 24 hour period. These results suggest the existence of diurnal CSF beta-endorphin variations analogous to those observed in plasma.

Increasing use of soyfoods and their potential role in cancer prevention.

The United States produces approximately half of the world's soybeans. Although most of what is produced is used as animal feed, soy-protein products (eg, soy-protein flour, concentrates, and isolates) are used extensively by the food industry, primarily for their functional characteristics, such as emulsification. During the past decade, however, there has been a marked increase in the use of both traditional soyfoods, such as tofu and soymilk, and second-generation soyfoods, products which generally simulate familiar American dishes. Recently, attention has focused on the possible role of soybean consumption in reducing cancer risk. Soybeans contain, in relatively high concentrations, several compounds with demonstrated anticarcinogenic activity. Two of these compounds--protease inhibitors and phytic acid--have traditionally been viewed as antinutrients. The scientific community has begun to appreciate the potential importance of nonnutritive dietary compounds (phytochemicals) in foods such as soybeans. Dietitians need to become more aware of the phytochemical content of foods and the possible effect of phytochemicals on health and disease.

Considerations in planning vegan diets: children.

This article reviews research on the growth and nutrient intake of vegan children and provides guidelines for counselling parents of vegan children. Although diets of vegan children meet or exceed recommendations for most nutrients, and vegan children have higher intakes of fiber and lower intakes of total fat, saturated fat, and cholesterol than omnivore children, some studies indicate that they may be low in calcium. In addition, bioavailability of zinc and iron from plant foods can be low. Protein needs are slightly higher for vegan children but are easily met with a varied diet that provides adequate energy. Special attention should be given to dietary practices that enhance absorption of zinc and iron from plant foods. Further, good sources of the omega-3 fatty acid linolenic acid should be emphasized to enhance synthesis of the long-chain fatty acid docosahexanoic acid. Dietetics professionals who counsel vegan families should help parents identify good sources of vitamin B-12, riboflavin, zinc, calcium and, if sun exposure is not adequate, vitamin D. This should not be problematic, due to the growing number and availability of fortified vegan foods that can help children meet all nutrient needs. Therefore, with appropriate food choices, vegan diets can be adequate for children at all ages.

Considerations in planning vegan diets: infants.

Appropriately planned vegan diets can satisfy nutrient needs of infants. The American Dietetic Association and The American Academy of Pediatrics state that vegan diets can promote normal infant growth. It is important for parents to provide appropriate foods for vegan infants, using guidelines like those in this article. Key considerations when working with vegan families include composition of breast milk from vegan women, appropriate breast milk substitutes, supplements, type and amount of dietary fat, and solid food introduction. Growth of vegan infants appears adequate with post-weaning growth related to dietary adequacy. Breast milk composition is similar to that of non-vegetarians except for fat composition. For the first 4 to 6 months, breast milk should be the sole food with soy-based infant formula as an alternative. Commercial soymilk should not be the primary beverage until after age 1 year. Breastfed vegan infants may need supplements of vitamin B-12 if maternal diet is inadequate; older infants may need zinc supplements and reliable sources of iron and vitamins D and B-12. Timing of solid food introduction is similar to that recommended for non-vegetarians. Tofu, dried beans, and meat analogs are introduced as protein sources around 7-8 months. Vegan diets can be planned to be nutritionally adequate and support growth for infants.

Humoral immunity and lymphocyte subpopulations in patients with dilated cardiomyopathy.

The incidence of serum organ and non-organ specific autoantibodies, the peripheral blood lymphocyte blastogenic response to phytohaemagglutinin, concanavalin A and pokeweek mitogen, and the surface markers of peripheral T and B lymphocytes were studied in 15 patients affected by coronary artery disease and in 21 patients with dilated cardiomyopathy. In the latter group there was a significantly impaired blastogenic response to concanavalin A with respect to both the normal control group and patients with coronary artery disease (P less than 0.01). The percentage of peripheral blood lymphocytes with cytotoxic/suppressor activity was also reduced in patients with dilated cardiomyopathy in comparison to normal subjects and patients with coronary artery disease (P less than 0.01 and P less than 0.05, respectively). These data may reflect an in vivo defect in suppressor cell function in patients with dilated cardiomyopathy.

Diagnosis of HCV related acute hepatitis by serial determination of IgM to HCV: a preliminary observation.

OBJECTIVE: To verify whether serial determination of titre of IgM to HCV core protein (HCV IgM) may be useful to distinguish acute hepatitis C (AHC) from reactivation of chronic hepatitis C (r-CHC), we studied 18 consecutive patients with AHC (identified by seroconversion to anti-HCV) and 15 consecutive patients who had been anti-HCV positive for at least one year at the time of reactivation. METHODS: Samples of serum were obtained from all patients on hospitalisation and every 5 days during the follow-up and stored at -80 degrees C: 54 samples of serum for the AHC group and 41 for the r-CHC group. Titres of HCV IgM were calculated as Index values by a commercially available enzyme immunoassay (HCV-IgM EIA 2.0, Abbott Laboratories, North Chicago, IL, USA). RESULTS: No difference was observed between the two groups of patients as regards age, sex, risk factors for the acquisition of HCV infection, clinical and biochemical data on presentation, prevalence of cases with detectable viremia or distribution of HCV genotypes. HCV IgM was detected with an Index value of 350 or more in only 1 (6.7%) in the r-CHC group and in 17 (94.4%) in the AHC group (p<0.01). Moreover, during the early phase of the illness we observed a wide variation in the HCV IgM Index values in AHC and consistent values in r-CHC. CONCLUSIONS: Our data indicate that AHC is characterised by high and variable titres of HCV IgM during the acute phase of the illness, which may be considered diagnostic, whereas in r-CHC the IgM titre remains stable and rarely reaches a high level.

Decision-making ability and advance directive preferences in nursing home patients and proxies.

We studied 39 nursing home patients and proxies to assess their decision-making capability and preferences regarding advance directives (ADs) or "living wills." Most patients willingly stated preferences; over half opted to forego burdensome measures when death appeared imminent. Patients perceived as decisionally capable were more likely to forego life-sustaining measures than those of questionable capability. The vast majority of proxies disapproved of using life-sustaining measures, even in some cases with limited knowledge of patients' preferences.

Nutritional implications of dietary phytochemicals.

Although increasing the levels of phytochemicals in foods via traditional breeding or genetic engineering would appear to pose less of a risk, there is still the possibility of over consumption given the ease with which phytochemical content can be increased. According to the recent position paper by the American Dietetic Association on phytochemicals, "the dietetics professional ... is the specialist who should make recommendations concerning appropriate dietary intake to optimize the potential benefits of phytochemical-rich or functional foods in overall health." For dietitians to make these recommendations, it will be necessary for the nutrition community to make a concerted effort to incorporate information on phytochemicals into nutrition manuals and professional resources. As it is, most of the research and discussion of phytochemicals is conducted by professionals not related or only peripherally related to the field of nutrition. This is truly an exciting time to be involved in the nutrition field. We have moved a head from thinking that only a relatively small number of dietary factors possess biological activity to recognizing that there are hundreds and perhaps thousands of such factors. It will be many years before our understanding of phytochemicals approaches our knowledge of vitamins and minerals- and it is worth nothing that our knowledge of vitamins and minerals is still incomplete. But it does appear that the phytochemicals help explain why plant-based diets, in general, are associated with a reduced risk of many chronic diseases. And in fact, his may be the most important outcome from use of phytochemicals. The nutrition community now has more reasons for encouraging consumers to eat plant-based diets.

Effects of nicardipine on intimal-medial thickness and arterial distensibility in hypertensive patients. Preliminary results after 6 months.

BACKGROUND: The aim of this study was to evaluate the effects of nicardipine, at the dosage of 80 mg/day in two administrations, on blood pressure, intimal-media thickness of the common carotid artery and on arterial distensibility after 6 months of therapy. The study population consisted of 23 patients, 13 male and 10 female, mean age 61.7 +/- 10.1 years, with systolic blood pressure 170.4 +/- 14.5 mmHg and diastolic blood pressure 98.3 +/- 5.7 mmHg, affected by essential arterial hypertension of slight to moderate degree. Twenty-three subjects underwent high resolution B-mode echotomography of the common carotid artery, performed twice by the same operator within a one-week period. Treatment for 6 months with slow release Nicardipine at a dosage of 80 mg in two daily administrations was seen to be efficient in reducing systolic and diastolic blood pressure values. It also reduced the carotid-femoral pulse wave velocity. The results of our study show that 6 month's treatment with slow-release Nicardipine at 80 mg in two daily administrations, in effective reducing systolic and diastolic blood pressure values, and, to a slightly significant degree, in reducing the value of the intimal-medial thickness of the common carotid. Naturally the data which emerge from our study are preliminary and require a definitive analysis at the end the study, which is foreseen after a two year period from the enrolment of at least one hundred patients.

Effects of hypertension on intimal-medial thickness, left ventricular mass and aortic distensibility.

The aim of the study was to evaluate arterial distensibility, intimal-medial thickening of the common carotid artery, left ventricular mass and the eventual correlations among these parameters in the hypertensive state. Our study population consisted of 89 hypertensive patients aged 35 to 80 years (mean age 60.8 +/- 10.6 years), and 76 normotensive subjects aged 45 to 85 years (mean age 61.2 +/- 11.1 years). Those patients constantly presenting systolic blood pressure values > or = 160 mmHg or diastolic blood pressure > 90 mmHg were diagnosed as hypertensive. Each patient underwent a B-mode echotomographic examination of the extracranial carotid tract performed with a Vingmed CFM 750 echotomographer with a 7.5 MHz probe and M-mode echocardiography with a Vingmed CFM 750 device equipped with a 3.0 MHz transducer. The results show the intimal-media thickness value in hypertensive patients (0.90 +/- 0.22 mm on the right and 0.92 +/- 0.22 mm on the left), was significantly greater than that in normotensive subjects (0.64 +/- 0.13 mm on the right and 0.64 +/- 0.13 mm on the left, p < 0.001); in hypertensive subjects, interventricular septum thickness (12.1 +/- 1.25 mm) was significantly greater than that in normotensive patients (9.1 +/- 0.77 mm, p < 0.001). In conclusion, we can say that hypertensive subjects have higher values of common carotid artery intimal-medial thickness than normotensives and that this finding is associated with the presence of left ventricular hypertrophy and with a reduction in arterial compliance. Vascular ultrasonography, as well as echocardiography and arterial mechanography can show, in hypertensive subjects, cardiac and vascular abnormalities in a non invasive way.