Successful lactation induction in non-pregnant gilts.

A protocol to induce lactation was applied to non-pregnant gilts. In Experiment I, five gilts with oestrus synchronized through oral supplementation of 20 mg altrenogest for 18 days received: 10 mg oestradiol cypionate (EC) on the last day of oestrous expression (D0); 10 mg EC and 300 mg long-acting progesterone (P4) on D26; and two 0.53 mg doses of a prostaglandin F2α analogue (PGF) 12 h apart on D36. Blood was collected on D12, D19, D26 and D33. Milk secretion started in all gilts 24 h after PGF administration and lasted at least 8 days. Milk samples were collected from D37 to D45. The serum P4 concentration was lower on D12 than subsequently (p < .05), but the oestradiol concentration was unaltered (p > .05). The milk produced during the induced lactation was generally richer in protein and poorer in fat compared to the milk from the lactation of a reference sow. In Experiment II, the same protocol induced lactation in two gilts, which nursed fostered piglets for 22 days. Thus, lactation was induced in all treated gilts and the milk produced was capable to nurture fostered piglets.

Expression of steroidogenic enzymes and TGFß superfamily members in follicular cells of prepubertal gilts with distinct endocrine profiles.

Regulation of the transforming growth factor beta (TGFß) superfamily by gonadotrophins in swine follicular cells is not fully understood. This study evaluated the expression of steroidogenic enzymes and members of the TGFß superfamily in prepubertal gilts allocated to three treatments: 1200 IU eCG at D -3 (eCG); 1200 IU eCG at D -6 plus 500 IU hCG at D -3 (eCG + hCG); and the control, composed of untreated gilts. Blood samples and ovaries were collected at slaughter (D0) and follicular cells were recovered thereafter. Relative gene expression was determined by real-time PCR. Serum progesterone levels were greater in the eCG + hCG group compared with the other groups (P < 0.01). No differences were observed in the expression of BMP15, BMPR1A, BMPR2, FSHR, GDF9, LHCGR and TGFBR1 (P > 0.05). Gilts from the eCG group presented numerically greater mean expression of CYP11A1 mRNA than in the control group that approached statistical significance (P = 0.08) and greater expression of CYP19A1 than in both the eCG and the control groups (P < 0.05). Expression of BMPR1B was lower in the eCG + hCG treatment group compared with the control (P < 0.05). In conclusion, eCG treatment increased the relative expression of steroidogenic enzymes, whereas treatment with eCG + hCG increased serum progesterone levels. Although most of the evaluated TGFß members were not regulated after gonadotrophin treatment, the downregulation of BMPR1B observed after treatment with eCG + hCG and suggests a role in luteinization regulation.

Expression of genes associated with fertility in the uterus and oviduct of heifers challenged with lipopolysaccharide.

Lipopolysaccharide (LPS) endotoxemia has been negatively associated with fertility. This study aimed to investigate the effect of LPS-induced inflammation on gene expression associated with bovine fertility in the uterus and oviduct. Sixteen healthy heifers were divided into two groups. The LPS group (n = 8) received two intravenous (i.v.) injections of 0.5 µg/kg of body weight of LPS with a 24-h interval, and the control group (n = 8) received two i.v. injections of saline solution with the same interval of time. All the animals had the follicular wave synchronized. Three days after the second injection of LPS, all animals were slaughtered and uterine and oviduct samples were collected. Gene expression associated with inflammatory response, thermal and oxidative stresses, oviduct environment quality, and uterine environment quality was evaluated. Body temperature and leucogram demonstrated that LPS induced an acute systemic inflammatory response. In the uterus, the expression of PTGS2 and NANOG genes was downregulated by the LPS challenge. However, no change in expression was observed in the other evaluated genes in the uterus, nor those evaluated in the oviduct. In conclusion, the inflammatory process triggered by LPS did not persist in the uterus and oviduct 3 days after challenge with LPS. Nonetheless, reduction in PTGS2 and NANOG expression in the uterus suggested that, indirectly, LPS may have a prolonged effect, which may affect corpus luteum and endometrial functions.

Sodium and salt content of Portuguese rolls produced in a city of southern Brazil: a comparison of laboratory analysis, food labelling and nutrition standards.

OBJECTIVE: To analyse the Na content of bread by comparing the amount of salt and Na among the label, laboratory analysis and international guidelines. DESIGN: Ten selected bakeries provided 3239 randomly selected samples of bread, which were weighed on-site. Triplicate samples were retrieved from each bakery (thirty samples) for analysis. Bread production was observed, and ingredient labels were queried to determine salt weights, which were used for comparison with the laboratory analysis. Flame photometry and the method for chlorides were utilised for analysing Na. Laboratory findings were compared to nine different international nutritional guidelines for Na consumption. SETTING: Florianopolis, south of Brazil. PARTICIPANTS: Ninety independent bakeries locally producing Portuguese rolls were queried; rolls from ten conveniently selected bakeries were retrieved for further analysis. RESULTS: The average weight of the rolls was 50·2 ± 5·3 g. The average amount of salt (g) per roll, by laboratory and label analyses, was 0·69 ± 0·0 and 0·62 ± 0·1 g, respectively. The mean level of Na (mg) reported on nutrient labels (478·2 ± 93·4/100 g) was significantly lower than by laboratory analysis (618·2 ± 73·8/100 g), P < 0·001. There was a difference for Na in rolls produced in the bakeries considering the unit weight of rolls (P ≤ 0·001) per 100 g (P = 0·026) and the mode of production. The consumption of two averaged units of rolls was equivalent to 51·7 % of the Brazilian guideline daily amount for Na for children and 31 % for adults. CONCLUSIONS: The nutrient labels underreported Na values. This study strengthens the importance of monitoring Na of breads in Brazil.

Stealth Magnetoliposomes Based on Calcium-Substituted Magnesium Ferrite Nanoparticles for Curcumin Transport and Release.

Despite the promising pharmacological properties of curcumin, the transport and effective release of curcumin is still a challenge. The advances in functionalized nanocarriers for curcumin have also been motivated by the anticancer activity of this natural compound, aiming at targeted therapies. Here, stealth (aqueous and solid) magnetoliposomes containing calcium-substituted magnesium ferrite nanoparticles, CaxMg1-xFe2O4 (with x = 0.25, 0.50, 0.75) were developed as nanocarriers for curcumin. The magnetic nanoparticles exhibit superparamagnetic properties and crystalline structure, with sizes below 10 nm. The magnetoliposomes based on these nanoparticles have hydrodynamic diameters around or below 150 nm and a low polydispersity. The influence of an alternating magnetic field (AMF) on drug release over time was evaluated and compared with curcumin release by diffusion. The results suggest the potential of drug-loaded magnetoliposomes as nanocarriers that can be magnetically guided to the tumor sites and act as agents for a synergistic effect combining magnetic hyperthermia and controlled drug release.

Prostaglandin F2α-induced luteolysis involves activation of Signal transducer and activator of transcription 3 and inhibition of AKT signaling in cattle.

Prostaglandin F2α (PGF) induces the precipitous loss of steroidogenic capabilities and cellular death in the corpus luteum of many species, yet the molecular mechanisms underlying this event are not completely understood. Signal transducer and activator of transcription 3 (STAT3) was activated in granulosa cells during follicle atresia, whereas AKT is immediately down-regulated in the corpus luteum after PGF treatment in cattle; however, their involvement in both functional and morphological luteolysis in monovular species still need to be determined. Blood samples and corpus lutea were collected from cows before (0) and 2, 12, 24, and 48 hr after PGF treatment on Day 10 of the estrous cycle (4-5 cows per time point). Serum progesterone concentrations decreased by threefold (p < 0.05) within 2 hr, confirming functional luteolysis. The mRNA abundance of the pro-apoptotic gene BAX increased 12-48 hr post-PGF treatment (p < 0.05), while morphological luteolysis was observed 24 and 48 hr after PGF treatment, based on the loss of plasma membrane integrity, reduction of cytoplasmic volume, and pyknotic nuclei. Phosphorylated STAT3 increased, peaking at 12 hr, and remained elevated until 48 hr after PGF treatment. SOCS3 transcript abundance also increased (p < 0.05) starting at 2 hr post-PGF treatment. In contrast, AKT phosphorylation decreased by 12 hr after treatment. Thus, activation of STAT3 and inactivation of AKT signaling are involved in structural regression of the corpus luteum.

Neonatal oxidative stress depends on oxygen blood pressure in umbilical artery.

With advancing gestation, partial pressure of oxygen (pO2) and pH fall significantly. Hypoxia is a main factor inducing free radical generation and thereby oxidative stress (OS). Placental and fetal tissue response when oxygen becomes restricted is complex and partially known. We tested the hypothesis that changes in umbilical artery and vein blood gas concentrations modulate OS occurrence in the newborn. Seventy umbilical artery and vein plasma samples were collected from healthy term newborns immediately after delivery. F2 Isoprostanes (F2-Isop) were measured in all samples as reliable markers of lipid peroxidation. Significantly lower pCO2 and higher pO2 and pH were found in umbilical vein than in artery, as expected. A positive correlation was detected between pH and pO2 only in umbilical artery (p=0.019). F2-Isop levels were no different between artery and vein in cord blood. Significant correlations were found between F2-Isop and pCO2 (p=0.025) as well as between F2-Isop and pH in umbilical vein (p=0.027). F2-Isop correlated with pCO2 (p=0.007) as well as with pO2 values (p=0.005) in umbilical artery blood. Oxidative stress (OS) in newborns depends on oxygen concentrations in umbilical artery. OS biomarkers significantly correlate with pO2 and in umbilical artery but not in umbilical vein. In normoxic conditions fetal-maternal gas exchanges occurring in placenta re-establish normal higher oxygen levels in umbilical vein than artery, with a normal production of free radicals without any deleterious effects.

Vaccines for preventing herpes zoster in older adults.

BACKGROUND: Herpes zoster, also known as 'shingles', is a neurocutaneous disease characterised by the reactivation of the latent varicella zoster virus (VZV), the virus that causes chickenpox when immunity to VZV declines. It is an extremely painful condition that can last many weeks or months and it can significantly compromise the quality of life of affected individuals. The natural process of aging is associated with a reduction in cellular immunity and this predisposes older people to herpes zoster. Vaccination with an attenuated form of VZV activates specific T cell production avoiding viral reactivation. The Food and Drug Administration has approved a herpes zoster vaccine with an attenuated active virus for clinical use among older adults, which has been tested in large populations. A new adjuvanted recombinant VZV subunit zoster vaccine has also been tested. It consists of recombinant VZV glycoprotein E and a liposome-based AS01B adjuvant system. This new vaccine is not yet available for clinical use. OBJECTIVES: To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. SEARCH METHODS: For this 2015 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 9), MEDLINE (1948 to the 3rd week of October 2015), EMBASE (2010 to October 2015), CINAHL (1981 to October 2015) and LILACS (1982 to October 2015). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine with placebo or no vaccine, to prevent herpes zoster in older adults (mean age > 60 years). DATA COLLECTION AND ANALYSIS: Two review authors independently collected and analysed data using a data extraction form. They also performed 'Risk of bias' assessment. MAIN RESULTS: We identified 13 studies involving 69,916 participants. The largest study included 38,546 participants. All studies were conducted in high-income countries and included only healthy Caucasian individuals ≥ 60 years of age without immunosuppressive comorbidities. Ten studies used live attenuated varicella zoster virus (VZV) vaccines. Three studies tested a new type of vaccine not yet available for clinical use. We judged five of the included studies to be at low risk of bias.The incidence of herpes zoster, at up to three years of follow-up, was lower in participants who received the vaccine than in those who received a placebo: risk ratio (RR) 0.49; 95% confidence interval (CI) 0.43 to 0.56, risk difference (RD) 2%, number needed to treat to benefit (NNTB) 50; GRADE: moderate quality evidence. The vaccinated group had a higher incidence of mild to moderate intensity adverse events. These date came from one large study that included 38,546 people aged 60 years or older.A study including 8122 participants compared the new vaccine (not yet available) to the placebo; the group that received the new vaccine had a lower incidence of herpes zoster at 3.2 years of follow-up: RR 0.04, 95% CI 0.02 to 0.10, RD 3%, NNTB 33; GRADE: moderate quality evidence. The vaccinated group had a higher incidence of adverse events but most them were of mild to moderate intensity.All studies received funding from the pharmaceutical industry. AUTHORS' CONCLUSIONS: Herpes zoster vaccine is effective in preventing herpes zoster disease and this protection can last three years. In general, zoster vaccine is well tolerated; it produces few systemic adverse events and injection site adverse events of mild to moderate intensity.There are studies of a new vaccine (with a VZV glycoproteic fraction plus adjuvant), which is currently not yet available for clinical use.

Lack of FSH support enhances LIF-STAT3 signaling in granulosa cells of atretic follicles in cattle.

Subordinate follicles (SFs) of bovine follicular waves undergo atresia due to declining FSH concentrations; however, the signalling mechanisms have not been fully deciphered. We used an FSH-induced co-dominance model to determine the effect of FSH on signalling pathways in granulosa cells of the second-largest follicles (SF in control cows and co-dominant follicle (co-DF2) in FSH-treated cows). The SF was smaller than DF in control cows while diameters of co-DF1 and co-DF2 in FSH-treated cows were similar. The presence of cleaved CASP3 protein confirmed that granulosa cells of SFs, but not of DFs and co-DFs, were apoptotic. To determine the effect of FSH on molecular characteristics of the second-largest follicles, we generated relative variables for the second largest follicle in each cow. For this, variables of SF or co-DF2 were divided by the variables of the largest follicle DF or co-DF1 in each cow. There was higher transcript abundance of MAPK1/3 and AKT1/2/3 but lower abundance of phosphorylated MAPK3/1 in SF than co-DF2 granulosa cells. Abundance of mRNA and phosphorylated protein of STAT3 was higher in granulosa cells of control SF than FSH-treated co-DF2. SF granulosa cells had higher levels of LIFR and IL6ST transcripts, the two receptors involved in STAT3 activation. Further, lower transcript abundance of interleukin 6 receptor (IL6R), another receptor involved in STAT3 activation, indicated that STAT3 activation in SF granulosa cells could be mainly due to leukemia inhibitory factor (LIF) signalling. These results indicate that atresia due to lack of FSH is associated with activated LIF-STAT3 signalling in SF granulosa cells, as FSH treatment reversed such activation.

Magnetic liposomes based on nickel ferrite nanoparticles for biomedical applications.

Nickel ferrite nanoparticles with superparamagnetic behavior at room temperature were synthesized using a coprecipitation method. These magnetic nanoparticles were either covered with a lipid bilayer, forming dry magnetic liposomes (DMLs), or entrapped in liposomes, originating aqueous magnetoliposomes (AMLs). A new and promising method for the synthesis of DMLs is described. The presence of the lipid bilayer in DMLs was confirmed by FRET (Förster Resonance Energy Transfer) measurements between the fluorescent-labeled lipids NBD-C12-HPC (NBD acting as a donor) included in the second lipid layer and rhodamine B-DOPE (acceptor) in the first lipid layer. An average donor-acceptor distance of 3 nm was estimated. Assays of the non-specific interactions of magnetoliposomes with biological membranes (modeled using giant unilamellar vesicles, GUVs) were performed. Membrane fusion between both aqueous and dry magnetoliposomes and GUVs was confirmed by FRET, which is an important result regarding applications of these systems both as hyperthermia agents and antitumor drug nanocarriers.

Streptomyces ansochromogenes Tur-10 produces a substance with antifungal bioactivity.

The increased incidence of fungal infections and the development of drug resistance have led to the search for microorganisms capable of producing bioactive metabolites with antifungal activity. Among these microorganisms, Streptomyces spp are distinguished mainly owing to their potential to secrete bioactive molecules. The aim of this study was to evaluate the production of secondary metabolites by Streptomyces sp TUR-10 against 12 fungal clinical isolates (yeast and filamentous fungi). In the preliminary screening, Streptomyces sp TUR-10 showed activity against 75% of the clinical isolates, and was selected for fermentation. In this assay, we tested three different media (MPE, M1, and ISP-4) for 96 h at pH 7.0 and 30°C for the production of bioactive metabolites. Increased production of bioactive compounds was observed when using the MPE medium for 48 h, with good activity against Candida pelliculosa. The minimum inhibitory concentration showed significant antifungal activity values ranging from 15.6 to 250 µg/mL. The actinobacterium was characterized by 16S rRNA analysis and the pattern suggested that the isolate studied belonged to the species Streptomyces ansochromogenes. The biotechnological potential of this strain was also demonstrated by the detection of the nrps and pks genes. These results indicate the production of secondary metabolites of biotechnological interest by actinobacteria from the rhizosphere, suggesting great potential for further research.

Mechanistic target of rapamycin (MTOR) signaling during ovulation in mice.

A complex network of endocrine/paracrine signals regulates granulosa-cell function in ovarian follicles. Mechanistic target of rapamycin (MTOR) has recently emerged as a master intracellular integrator of extracellular signals and nutrient availability. The objectives of the present study were to characterize the expression pattern and kinase activity of MTOR during follicular and corpus luteum development, and to examine how inhibition of MTOR kinase activity affects preovulatory maturation of ovarian follicles. MTOR expression was constitutive throughout follicular and corpus luteum development. Gonadotropins induced MTOR kinase activity in the ovary, which was inhibited by rapamycin treatment (10 µg/g body weight, intraperitoneal injection). Inhibition of human chorionic gonadotropin (hCG)-induced MTOR activity during preovulatory follicle maturation did not change key events of ovulation. Granulosa cells of rapamycin-treated mice showed reduced MTOR kinase activity at 1 and 4 hr post-hCG and overexpression of hCG-induced ovulation genes at 4 hr post-hCG. Overexpression of these ovulatory genes was associated with hyper-activation of extracellular signal-regulated kinase 1/2 (ERK1/2), which occurred in response to inhibition of MTOR with rapamycin and suggested that MTOR may function as a negative regulator of the mitogen-activated protein kinase (MAPK) pathway. Indeed, simultaneous inhibition of MTOR and ERK1/2 activities during preovulatory follicle maturation caused anovulation. Inhibition of hCG-induced ERK1/2 activity alone suppressed MTOR kinase activity, indicating that MAPK pathway is upstream of MTOR. Thus, normal ovulation appears to be a result of complex interactions between MTOR and MAPK signaling pathways in granulosa cells of ovulating follicles in mice.

Beta-blockers for preventing stroke recurrence.

BACKGROUND: Stroke affects 15 million people per year worldwide. Despite recent developments in acute stroke treatment, prevention remains very important. Stroke has a high rate of recurrence; therefore secondary prevention is also important. Many clinical approaches to control risk factors have been proposed. One of these approaches is the prescription of beta-blockers that have effects beyond the reduction of blood pressure, which can reduce the recurrence of stroke. OBJECTIVES: To evaluate the efficacy of beta-blockers for preventing stroke recurrence and for reducing death and major vascular events in people with a previous stroke or transient ischaemic attack (TIA), and to determine their safety, particularly with regard to the development of diabetes mellitus. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (December 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR) (The Cochrane Library 2011, Issue 12), the Database of Abstracts of Reviews of Effects (DARE) (December 2011), MEDLINE (1966 to December 2011), EMBASE (1980 to December 2011), and Latin American and Caribbean Health Sciences Literature (LILACS) (1982 to December 2011). We also searched ongoing trials registers and reference lists. SELECTION CRITERIA: Randomised controlled trials (RCTs) that included participants with previous stroke or TIA due to arterial thrombosis or embolism.The intervention was any beta-blocker versus control, or beta-blocker plus other treatment versus other treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the trials identified, appraised quality, and extracted data. MAIN RESULTS: We included two RCTs involving 2193 participants in the review. Both studies randomised participants to either beta-blocker (atenolol 5 mg) or placebo. No statistical differences were noted among the groups in risks of fatal and non-fatal stroke (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.75 to 1.17). For all other outcomes analysed (death from all causes, cardiac death, non-fatal myocardial infarction, major vascular events), we observed no significant differences between the groups. AUTHORS' CONCLUSIONS: To date, no available evidence supports the routine use of beta-blockers for secondary prevention after stroke or TIA. More studies with larger samples are needed.

Restoration and recovery of hurricane-damaged mangroves using the knickpoint retreat effect and tides as dredging tools.

In 2001, a hurricane moved a large sand dune, blocking the sole outlet channel of a mangrove. In the absence of daily tidal flow, the two ponds containing the mangrove vegetation evaporated, the secondary drainage channels were lost, and a salt crust formed on the bed of the ponds. The mangrove lost most of its trees and the remaining suffered from osmotic shock that led to defoliation. Restoration involved creating a knickpoint retreat (waterfall retreat effect) and tidal flow as a dredging mechanism to restore the outlet and form secondary channels in the ponds. During a very low tide, we deepened the mouth of the outlet channel by 1 m below high tide level to form a small waterfall when high tides receded. During successive tides, this one-step knickpoint deteriorated and formed a series of low rapids. With a steep gradient, the rapids retreated upstream into the ponds, first reopening the outlet channel and then carving new secondary channels in the pond mud flat. The excavation process of the outlet channel was repeated three times and was sufficient to effectively improve the hydrology of the entire pond system; allowing adequate flooding and draining of the mangrove ponds. Hydrology analysis tested by the Engelund-Hansen sediment transport formula established that the output of sediment from the ecosystem is greater than the input of sand into the mangroves. This is keeping the main channel continuously open. After eight years, tidal flow continues to keep the channels open; the salt crust has disappeared; the trees have recovered, and a large area of new vegetation has emerged.

GnRH34 with or without estradiol cypionate in timed AI in Bos indicus beef cows.

Two experiments were performed to evaluate the effects of GnRH treatment on the fertility of suckled Nelore beef cows treated with an estradiol/progesterone (E2/P4)-based protocol for timed artificial insemination (TAI). Experiment 1 focused on determining the effects of estradiol cypionate (EC) on ovulation in TAI cows treated with GnRH 34 h after removal of the intravaginal P4 device (IPD). Suckled cows (n = 26) were treated with 2 mg estradiol benzoate (EB) and IPD containing 1 g P4. After 8 days, IPDs were removed, and all cows were treated with 150 µg of d-cloprostenol (prostaglandin F2 alpha analog) and 300 IU of equine chorionic gonadotropin (eCG), then separated into two treatment groups consisting of cows who received 1) saline 0.9% i.m. (GnRH34 group) or 2) 0.6 mg i.m. of EC (EC-GnRH34 group). On day 9 (05:00 p.m.), all cows were given GnRH (10.5 µg of buserelin acetate) i.m. No differences were observed between the groups (P > 0.05) in the time of ovulation after IPD removal or in the proportion of cows ovulating. Experiment 2 focused on determining the effects of GnRH34 along with or in the absence of EC on day 8 on pregnancy per AI (P/AI) in postpartum beef cows. Cows (n = 981) were treated similarly to those in Experiment 1, but an additional group, the EC-GnRH48 group, was included, in which cows received EC on day 8 whereas those that did not show estrus received GnRH at TAI. Thus, in this experiment, groups consisted of GnRH34 (n = 322), EC-GnRH34 (n = 335), and EC-GnRH48 (n = 324). A higher rate of estrus expression was observed in cows treated with EC following IPD removal (EC-GnRH34: 69%, EC-GnRH48: 64.8%) than in cows in the GnRH34 group (45.6%). No difference in P/AI was observed between the treatment groups (P = 0.45), but P/AI in cows in the EC-GnRH34 group (64.2%) tended to be greater (P = 0.1) than in cows in the GnRH34 group (58%). In summary, although ovulation synchrony did not differ among the groups, P/AI in cows treated with EC and GnRH 34 h after IPD removal tended to be greater than in cows treated solely with GnRH; this was most likely due to a shorter proestrus/estrus period, considering the lower proportion of cows that displayed estrus in the GnRH34 group. Finally, given that P/AI did not differ between the EC-GnRH34 and EC-GnRH48 groups, our results suggest that, for cows not displaying estrus, administration of EC at the time of IPD removal followed by treatment with GnRH 48 h afterward represents the most cost-efficient TAI strategy for South American Zebu-based beef operations.

17α-estradiol does not adversely affect sperm parameters or fertility in male mice: implications for reproduction-longevity trade-offs.

17α-estradiol (17α-E2) is referred to as a nonfeminizing estrogen that was recently found to extend healthspan and lifespan in male, but not female, mice. Despite an abundance of data indicating that 17α-E2 attenuates several hallmarks of aging in male rodents, very little is known with regard to its effects on feminization and fertility. In these studies, we evaluated the effects of 17α-E2 on several markers of male reproductive health in two independent cohorts of mice. In alignment with our previous reports, chronic 17α-E2 treatment prevented gains in body mass, but did not adversely affect testes mass or seminiferous tubule morphology. We subsequently determined that chronic 17α-E2 treatment also did not alter plasma 17ß-estradiol or estrone concentrations, while mildly increasing plasma testosterone levels. We also determined that chronic 17α-E2 treatment did not alter plasma follicle-stimulating hormone or luteinizing hormone concentrations, which suggests 17α-E2 treatment does not alter gonadotropin-releasing hormone neuronal function. Sperm quantity, morphology, membrane integrity, and various motility measures were also unaffected by chronic 17α-E2 treatment in our studies. Lastly, two different approaches were used to evaluate male fertility in these studies. We found that chronic 17α-E2 treatment did not diminish the ability of male mice to impregnate female mice, or to generate successfully implanted embryos in the uterus. We conclude that chronic treatment with 17α-E2 at the dose most commonly employed in aging research does not adversely affect reproductive fitness in male mice, which suggests 17α-E2 does not extend lifespan or curtail disease parameters through tradeoff effects with reproduction.

FGF10 inhibits dominant follicle growth and estradiol secretion in vivo in cattle.

Fibroblast growth factors (FGFs) are involved in paracrine control of follicle development. It was previously demonstrated that FGF10 decreases estradiol (E(2)) secretion in granulosa cell culture and that theca cell FGF10 mRNA expression is decreased in healthy follicles from abattoir ovaries. The main objectives of this study were to evaluate FGF10 and FGFR2b mRNA expression during follicular development in vivo, to evaluate the effect of FGF10 on follicle growth using Bos taurus taurus cows as a model, and to gain more insight into the mechanisms through which FGF10 inhibits steroidogenesis. Messenger RNA encoding both FGF10 and FGFR2b (main FGF10 receptor) was significantly more expressed in subordinate follicles (SFs) than in dominant follicles (DFs). The intrafollicular injection of FGF10 into the largest growing follicle at 7-8 mm in diameter interrupted the DF growth in a dose-dependent manner (11±0.4, 8.3±1 and 5.9±0.3 mm for 0, 0.1, and 1 µg/ml FGF10, respectively, at 72 h after treatment; P<0.05). In a third experiment, follicles were obtained 24 h after FGF10 (1 µg/ml) or PBS treatment through ovariectomy. In theca cells, FGF10 treatment did not affect mRNA encoding steroidogenic enzymes, LHCGR and IGFBPs, but significantly upregulated FGF10 mRNA expression. The expression of CYP19A1 mRNA in granulosa cells was downregulated by FGF10 treatment, which was accompanied by a 50-fold decrease in E(2) production, and decreased cyclin D2 mRNA. These results have shown that FGF10 and its receptor FGFR2b are more expressed in SFs and provide solid in vivo evidence that FGF10 acts as an important regulator of follicular growth in cattle.

Intratumoral lymphatic vessel density in vulvar squamous cell carcinomas: a possible association with favorable prognosis.

Lymphatic vessels serve as major routes for regional dissemination, and therefore, lymph node status is a key indicator of prognosis. To predict lymph node metastasis, tumor lymphatic density and lymphangiogenesis-related molecules have been studied in various tumor types. To our knowledge, no previous studies have evaluated the role of intratumoral lymphatic vessel density (LVD) in the behavior of vulvar carcinomas. The aim of this study was to analyze intratumoral LVD in relation to patient survival and well-characterized prognostic factors for cancer. Thirty-five patients with vulvar squamous cell carcinoma underwent vulvectomy and dissection of regional lymph nodes. Clinical records were reviewed, in addition to histological grade, peritumoral lymphatic invasion, and depth of infiltration for each case. Tissue microarray paraffin blocks were created, and lymphatic vessels were detected using immunohistochemical staining of podoplanin (D2-40 antibody). Intratumoral LVD was quantified by counting the number of stained vessels. Higher values for intratumoral LVD were associated with low-grade and low-stage tumors, and with tumors without lymphatic invasion and reduced stromal infiltration. In a univariate analysis, high intratumoral LVD was associated with a higher rate of overall survival and a lower rate of lymph node metastasis. Our results suggest that increased intratumoral LVD is associated with favorable prognosis in vulvar squamous carcinomas.

Exercise interventions for shoulder dysfunction in patients treated for head and neck cancer.

BACKGROUND: Shoulder dysfunction is a common problem in patients treated for head and neck cancer. Both neck dissections and radiotherapy can cause morbidity to the shoulder joint. Exercise interventions have been suggested as a treatment option for this population. OBJECTIVES: To evaluate the effectiveness and safety of exercise interventions for the treatment of shoulder dysfunction caused by the treatment of head and neck cancer. SEARCH METHODS: We searched the Cochrane ENT Group Trials Register; CENTRAL; PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the search was 7 July 2011. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing any type of exercise therapy compared with any other intervention in patients with shoulder dysfunction due to treatment of head and neck cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias and extracted data from studies. We contacted study authors for information not provided in the published articles. MAIN RESULTS: Three trials involving 104 people were included. We classified one study as having low risk of bias; the others had some limitations and we classified them as having high risk of bias.Two studies (one with low risk of bias and the other with high risk of bias) applied progressive resistance training (PRT) combined with range of motion exercises and stretching; the comparison group received standard care. Pooled data demonstrated that PRT can improve shoulder pain (mean difference (MD) -6.26; 95% confidence interval (CI) -12.20 to -0.31) and shoulder disability (MD -8.48; 95% CI -15.07 to -1.88), both measured using the Shoulder Pain and Disability Index (SPADI) (range 0 to 100). Similarly, secondary outcomes were also improved: active range of motion for external rotation (MD 14.51 degrees; 95% CI 7.87 to 21.14), passive range of motion for abduction (MD 7.65 degrees; 95% CI 0.64 to 14.66), forward flexion (MD 6.20 degrees; 95% CI 0.69 to 11.71), external rotation (MD 7.17 degrees; 95% CI 2.20 to 12.14) and horizontal abduction (MD 7.34 degrees; 95% CI 2.86 to 11.83). Strength and resistance of scapular muscles was assessed in one study and the results showed a statistically significant benefit of PRT. The studies did not demonstrate a statistically significant difference in quality of life. Only two non-serious adverse events were described in the PRT group compared with none in the standard care group.One study with high risk of bias used a broad spectrum of techniques including free active exercises, stretching and postural care for a period of three months following surgery. This study did not demonstrate a difference between the exercise group and routine postoperative physiotherapy care in shoulder function and quality of life, but serious methodological limitations could explain this. No serious adverse events were reported. AUTHORS' CONCLUSIONS: Limited evidence from two RCTs demonstrated that PRT is more effective than standard physiotherapy treatment for shoulder dysfunction in patients treated for head and neck cancer, improving pain, disability and range of motion of the shoulder joint, but it does not improve quality of life. However, although statistically significant the measured benefits of the intervention may be small. Other exercise regimes were not shown to be effective compared to routine postoperative physiotherapy. Further studies which apply other exercise interventions in head and neck cancer patients in the early postoperative and radiotherapy period are needed, with long-term follow-up.

Vaccines for preventing herpes zoster in older adults.

BACKGROUND: Herpes zoster or, as it is commonly called, 'shingles' is a neurocutaneous disease characterised by the reactivation of varicella zoster virus (VZV), the virus that causes chickenpox, which is latent in the dorsal spinal ganglia when immunity to VZV declines. It is an extremely painful condition which can often last for many weeks or months, impairing the patient's quality of life. The natural aging process is associated with a reduction of cellular immunity which predisposes to herpes zoster. Vaccination with an attenuated form of VZV activates specific T cell production, therefore avoiding viral reactivation. A herpes zoster vaccine with an active virus has been approved for clinical use among older adults by the Food and Drug Administration and has been tested in large populations. OBJECTIVES: To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. SEARCH METHODS: We searched the following sources for relevant studies: CENTRAL 2012, Issue 7, MEDLINE (1948 to July week 1, 2012), EMBASE (2010 to July 2012), LILACS (1982 to July 2012) and CINAHL (1981 to July 2012). We also reviewed reference lists of identified trials and reviews for additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine with placebo or no vaccine, to prevent herpes zoster in older adults (mean age > 60 years). DATA COLLECTION AND ANALYSIS: Two review authors independently collected and analysed data using a data extraction form. They also carried out an assessment of risk of bias. MAIN RESULTS: We identified eight RCTs with a total of 52,269 participants. Three studies were classified at low risk of bias. The main outcomes on effectiveness and safety were extracted from one clinical trial with a low risk of bias. Four studies compared zoster vaccine versus placebo; one study compared high-potency zoster vaccine versus low-potency zoster vaccine; one study compared refrigerated zoster vaccine versus frozen zoster vaccine; one study compared live zoster vaccine versus inactivated zoster vaccine and one study compared zoster vaccine versus pneumococcal polysaccharide vaccine (pneumo 23).Confirmed cases of herpes zoster were less frequent in patients who received the vaccine than in those who received a placebo: risk ratio (RR) 0.49 (95% confidence interval (CI) 0.43 to 0.56), with a risk difference (RD) of 2%, and number needed to treat to benefit (NNTB) of 50. Analyses according to age groups indicated a greater benefit in participants aged 60 to 69 years, RR 0.36 (95% CI 0.30 to 0.45) and in participants aged 70 years and over, RR 0.63 (95% CI 0.53 to 0.75). Vaccine-related systemic adverse effects were more frequent in the vaccinated group (RR 1.29, 95% CI 1.05 to 1.57, number needed to treat to harm (NNTH) = 100). The pooled data risk ratio for adverse effects for participants with one or more inoculation site adverse effect was RR 4.51 (95% CI 2.35 to 8.68), and the NNTH was 2.8 (95% CI 2.3 to 3.4). Side effects were more frequent in younger (60 to 69 years) than in older (70 years and over) participants. AUTHORS' CONCLUSIONS: Herpes zoster vaccine is effective in preventing herpes zoster disease. Although vaccine benefits are larger in the younger age group (60 to 69 years), this is also the age group with more adverse events. In general, zoster vaccine is well tolerated; it produces few systemic adverse events and injection site adverse effects of mild to moderate intensity.