Changes in serum and faecal zinc concentrations following supplementation with zinc sulphate heptahydrate of extensively grazed dairy cattle in New Zealand.

AIMS: To examine the relationship in dairy cattle between serum and faecal Zn concentrations and daily intake of Zn supplemented with an oral drench; and whether total daily intake (TDI) of Zn in dairy cattle can be predicted from single measurements of Zn concentration in serum or faeces. METHODS: A convenience sample of 20 animals from three stock classes (lactating cows, dry cows, heifers), that had not received Zn supplementation in the previous 60 days, was enrolled in the study. From Days -7 to -1, animals received no Zn supplementation. On Day 0, 15 animals per class were assigned daily drenching with increasing doses of ZnSO4.7H2O while five remained controls. From Days 0-6, treatment animals received 12.5 mg/kg LWT of Zn/day; from Days 7-13, 25 mg/kg LWT Zn/day and from Days 14-20, 37.5 mg/kg LWT Zn/day. Animals co-grazed within each stock class. Pasture, serum and faecal samples were collected at the start and at weekly intervals before each increase in Zn supplementation. Mixed and non-parametric models were used to assess treatment effects and whether daily intake of Zn could be predicted from Zn concentrations in serum and faeces. RESULTS: Dosing with 0, 12.5, 25.0 and 37.5 mg Zn/kg LWT resulted in serum Zn concentrations of 12.1, 16.7, 27.2 and 35.8 µmol/L in heifers, 13.3, 17.1, 26.4 and 40.0 µmol/L in dry and 11.9, 12.1, 23.4 and 27.2 µmol/L in lactating cows. Dosing with the same amounts of Zn resulted in faecal Zn concentrations of 2.95, 21.72, 40.32 and 53.27 mmol/kg DM in heifers, 2.81, 23.77, 55.16 and 68.20 mmol/kg DM in dry and 3.00, 12.71, 34.86 and 57.53 mmol/kg DM in lactating cows, respectively. Treatment elevated serum and faecal Zn concentrations above controls (p < 0.001). Supplemented lactating cows had lower serum Zn concentrations than dry cows or heifers (p < 0.01). Supplemented dry cows had faecal DM Zn concentrations higher than heifers or lactating cows (p < 0.05). Analysis showed serum and faecal Zn concentrations could predict TDI of Zn (p < 0.001). Concentrations of Zn in faeces estimated TDI of Zn within a narrower predictive interval than serum Zn concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Concentrations of Zn in serum and faeces were positively associated with TDI of Zn in dairy cattle and could predict TDI of Zn. When using serum and faecal Zn concentrations to estimate TDI Zn, stock class must be accounted for.

Atrial fibrillation after resection: a PROGRESS III study.

AIM: Atrial fibrillation (AF) is a common cardiac arrhythmia, and is associated with worsening quality of life and complications such as stroke. Previous work showed that 8% of patients develop new-onset AF following colonic resection and highlighted factors that might predict the development of postoperative AF. The development of a new arrhythmia may have a negative effect on longer-term quality of life as well as cancer survivorship. The aim of this study is to accurately quantify the incidence of AF following colorectal cancer surgery and to validate a model to predict its development. METHOD: The Atrial Fibrillation After Resection (AFAR) study will recruit 720 patients aged 65 or over undergoing resection of colorectal cancer with curative intent. The primary outcome is development of AF within 90 days of surgery. Assessment of cardiac rhythm will be performed using 24-h Holter monitors at baseline, 30 and 90 days after surgery. An electrocardiogram (ECG) will be performed on the day of discharge. Baseline descriptors including model variables and quality of life will be recorded using EQ-5D-5L. The occurrence of complications and other key surgical outcomes will be recorded. An additional blood test for N-terminal pro B-type natriuretic peptide (NT-proBNP) will be performed prior to surgery. Statistical analysis will validate a previously derived model and will test the incremental value of added variables such as NT-proBNP. Finally, an exploratory analysis will assess whether changes in ECG measures between baseline and postoperative ECG can predict subsequent new-onset AF. CONCLUSION: This study will provide data that may allow us to stratify the risk of developing AF following colorectal cancer surgery. This may inform screening or prophylactic approaches.

Non-randomized studies should be considered for assessing surgical techniques in rectal prolapse: prospective cohort study.

AIM: Randomized trials comparing surgical techniques for rectal prolapse are not always feasible. We assessed whether non-randomized comparisons of those who have had surgery with those still waiting would be confounding baseline health status. METHOD: This was a prospective cohort study in seven UK hospitals. Participants were ≥ 18 years and listed for surgical interventions of equivalent intensity for rectal prolapse. They were defined as short or long waiters (≤ 18 or > 18 weeks, respectively). Time on the waiting list was compared with baseline comorbidity (Charlson comorbidity index) and change from baseline in health status (EQ-5D-5L) at the time of surgery. RESULTS: In all, 203 patients were analysed. Median (interquartile range) waiting time was 13.7 weeks (8.1, 20.4) varying across sites. Baseline comorbidity was not an important predictor of waiting time. Median Charlson comorbidity index was 2 (0, 3) for short and 1 (0, 3) for long waiters. A change in waiting time by a week was associated with negligible improvement in the EQ-5D-5L index of 0.001 (95% CI -0.000 to 0.003, P = 0.106). CONCLUSION: Negligible change in patient reported health status while on the waiting list and lack of effect of comorbidities in influencing waiting time support the use of non-randomized pre-/post-studies to compare the effects of surgical interventions for rectal prolapse.

Penile lymphoedema: approach to investigation and management.

BACKGROUND: Penile lymphoedema (with and without cellulitis) is a rare, often chronic, clinically heterogeneous entity with an uncertain pathogenesis and an important differential diagnosis. It creates significant physical and psychosexual morbidity, and presents considerable therapeutic challenges. The existing literature is limited. AIM: To describe and share our updated cumulative experience of a cohort of patients with penile lymphoedema. METHODS: This was a retrospective review of the case records of patients with chronic penile lymphoedema seen in two dedicated male genital dermatology clinics between January 2011 and July 2016. RESULTS: In total, 41 cases were identified. Over a third had Crohn disease (CD) (which was occult in one-third of these), and over a third had serological evidence of streptococcal infection. All patients responded to systemic antibiotics and specialized urological surgery circumcision and excision). CONCLUSIONS: Penile lymphoedema should be investigated to exclude underlying pathology especially CD and streptococcal infection. Treatment with antibiotics should be considered early and long term to try to preserve the foreskin: most patients are uncircumcised. Some patients may benefit from a course or courses of oral steroids. The development of gross dysfunction of the prepuce usually dictates circumcision and excision of lymphoedematous tissue once the situation is medically stabilized.

Use of different somatic cell count cut-points to define intramammary infection at drying off in dairy cows from a herd with a high somatic cell count.

Aims: To assess the use of different cut-points based on individual cow somatic cell counts (SCC) to define cows with intramammary infection (IMI) at drying-of, in a herd with a high mean bulk tank SCC. Methods: Results for SCC from four herd tests during lactation and bacterial culture of milk samples collected before drying-off were obtained for 139 cows from a herd with an average bulk milk SCC of >300,000 cells/mL over the final 4 months of the 2006/07 lactation. Based on culture results, cows were defined as being infected with a major (Staphylococcus aureus, Streptococcus uberis or Nocardia spp.) or any pathogen. Receiver-operator characteristics (ROC) curves were used to determine optimum cut-points for maximum, average and last herd test SCC, for predicting IMI. Multivariable logistic regression models were used to determine which variables were associated with IMI, and the sensitivity (Se), specificity (Sp) and positive predictive value (PPV) were determined for different cut-points. Results: At the cow level, 75/139 (54.0%) cows had IMI with a major pathogen and 123/139 (88.5%) with any pathogen. A SCC ≥150,000 cells/mL at ≥2 herd tests and a SCC ≥299,000 cells/mL at the last herd test, for cows aged ≥4 years, were associated with IMI with a major pathogen at drying-off (p<0.05). A SCC ≥150,000 cells/mL at ≥2 herd tests was associated with IMI with any pathogen at drying-off (p<0.001). A cut-point of ≥150,000 cells/mL at any herd test had the highest Se (0.97 and 0.94), but the lowest Sp (0.19 and 0.44) and PPV (0.58 and 0.93) for infection with major and any pathogens, respectively. A cut-point of ≥150,000 cells/mL at ≥2 herd tests doubled the Sp and increased the PPV without large decreases in test Se for infection with either a major or any pathogen. Conclusions and clinical relevance: In this herd with a high bulk milk SCC, use of a cut-point of a SCC ≥150,000 cells/mL at any herd test to define IMI would be appropriate, where the goal at drying-off is to ensure that cows infected with any pathogen receive antimicrobial treatment. Where the goal is to reduce the use of antimicrobial dry cow therapy in uninfected cows while limiting the number of infected cows not being treated, use of a cut-point of SCC ≥150,000 cells/mL at ≥2 herd tests to define IMI may be more appropriate.

WDR45B-related intellectual disability, spastic quadriplegia, epilepsy, and cerebral hypoplasia: A consistent neurodevelopmental syndrome.

The advancement in genomic sequencing has greatly improved the diagnostic yield for neurodevelopmental disorders and led to the discovery of large number of novel genes associated with these disorders. WDR45B has been identified as a potential intellectual disability gene through genomic sequencing of 2 large cohorts of affected individuals. In this report we present 6 individuals from 3 unrelated families with homozygous pathogenic variants in WDR45B: c.799C>T (p.Q267*) in 1 family and c.673C>T (p.R225*) in 2 families. These individuals shared a similar phenotype including profound development delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations. Neuroimaging showed ventriculomegaly, reduced cerebral white matter volume, and thinning of cerebral gray matter. The consistency in the phenotype strongly supports that WDR45B is associated with this disease.

Evaluation of applying statistical process control techniques to daily average feeding behaviors to detect disease in automatically fed group-housed preweaned dairy calves.

Group housing and computerized feeding of preweaned dairy calves are gaining in popularity among dairy producers, yet disease detection remains a challenge for this management system. The aim of this study was to investigate the application of statistical process control charting techniques to daily average feeding behavior to predict and detect illness and to describe the diagnostic test characteristics of using this technique to find a sick calf compared with detection by calf personnel. This prospective cross-sectional study was conducted on 10 farms in Minnesota (n = 4) and Virginia (n = 6) utilizing group housing and computerized feeding from February until October 2014. Calves were enrolled upon entrance to the group pen. Calf personnel recorded morbidity and mortality events. Farms were visited either every week (MN) or every other week (VA) to collect calf enrollment data, computer-derived feeding behavior data, and calf personnel-recorded calf morbidity and mortality. Standardized self-starting cumulative sum (CUSUM) charts were generated for each calf for each daily average feeding behavior, including drinking speed (mL/min), milk consumption (L/d), and visits to the feeder without a milk meal (no.). A testing subset of 352 calves (176 treated, 176 healthy) was first used to find CUSUM chart parameters that provided the highest diagnostic test sensitivity and best signal timing, which were then applied to all calves (n = 1,052). Generalized estimating equations were used to estimate the diagnostic test characteristics of a single negative mean CUSUM chart signal to detect a sick calf for a single feeding behavior. Combinations of feeding behavior signals were also explored. Single signals and combinations of signals that included drinking speed provided the most sensitive and timely signal, finding a sick calf up to an average (±SE) of 3.1 ± 8.8 d before calf personnel. However, there was no clear advantage to using CUSUM charting over calf observation for any one feeding behavior or combination of feeding behaviors when predictive values were considered. The results of this study suggest that, for the feeding behaviors monitored, the use of CUSUM control charts does not provide sufficient sensitivity or predictive values to detect a sick calf in a timely manner compared with calf personnel. This approach to examining daily average feeding behaviors cannot take the place of careful daily observation.

Investigating the heterogeneity of alkylating agents' efficacy and toxicity between sexes: A systematic review and meta-analysis of randomized trials comparing cyclophosphamide and ifosfamide (MAIAGE study).

BACKGROUND: A marginal interaction between sex and the type of alkylating agent was observed for event-free survival in the Euro-EWING99-R1 randomized controlled trial (RCT) comparing cyclophosphamide and ifosfamide in Ewing sarcoma. To further evaluate this interaction, we performed an individual patient data meta-analysis of RCTs assessing cyclophosphamide versus ifosfamide in any type of cancer. METHODS: A literature search produced two more eligible RCTs (EICESS92 and IRS-IV). The endpoints were progression-free survival (PFS, main endpoint) and overall survival (OS). The hazard ratios (HRs) of the treatment-by-sex interaction and their 95% confidence interval (95% CI) were assessed using stratified multivariable Cox models. Heterogeneity of the interaction across age categories and trials was explored. We also assessed this interaction for severe acute toxicity using logistic models. RESULTS: The meta-analysis comprised 1,528 pediatric and young adult sarcoma patients from three RCTs: Euro-EWING99-R1 (n = 856), EICESS92 (n = 155), and IRS-IV (n = 517). There were 224 PFS events in Euro-EWING99-R1 and 200 in the validation set (EICESS92 + IRS-IV), and 171 and 154 deaths in each dataset, respectively. The estimated treatment-by-sex interaction for PFS in Euro-EWING99-R1 (HR = 1.73, 95% CI = 1.00-3.00) was not replicated in the validation set (HR = 0.97, 95% CI = 0.55-1.72), without heterogeneity across trials (P = 0.62). In the pooled analysis, the treatment-by-sex interaction was not significant (HR = 1.31, 95% CI = 0.89-1.95, P = 0.17), without heterogeneity across age categories (P = 0.88) and trials (P = 0.36). Similar results were observed for OS. No significant treatment-by-sex interaction was observed for leucopenia/neutropenia (P = 0.45), infection (P = 0.64), or renal toxicity (P = 0.20). CONCLUSION: Our meta-analysis did not confirm the hypothesis of a treatment-by-sex interaction on efficacy or toxicity outcomes.

Non-invasive assessment of muscle oxygenation may aid in optimising transfusion threshold decisions in ambulatory paediatric patients.

OBJECTIVE: To assess the potential utility of a novel non-invasive muscle oxygen measurement to determine the presence of muscle hypoxia in patients with anaemia. BACKGROUND: Recent assessment of the risk/benefit ratio of blood transfusion has led to clinical strategies optimising transfusion decisions. These decisions are primarily based on haematocrit (Hct) but not oxygen delivery, the primary function of red blood cells (RBCs). We hypothesised that muscle oxygenation (MOx) would correlate with Hct in patients with anaemia and may be a physiologically relevant determinant of the transfusion threshold. METHODS/MATERIALS: MOx was non-invasively determined in children in the Cancer and Blood Disorders Center ambulatory clinic at Seattle Children's Hospital using a custom-designed optical probe and spectrometer. MOx was compared with contemporaneous Hct. In subjects receiving RBCs, MOx and Hct were also determined following transfusion. RESULTS: MOx ranged from 36·7 to 100%, and Hct ranged from 17·0 to 38·6% in 27 measurements from 16 patients. High MOx values were associated with high Hct. Mean MOx for patients with normal Hct for age (n = 5) was 95·9 ± 2·9%. RBC transfusion increased mean Hct from 19·1 ± 1·5% to 29·3 ± 2·0 and mean MOx from 67·9 ± 21·1% to 89·9 ± 9·8%. Among six transfusion episodes (in five patients) with initial Hct < 22, only three had a pre-transfusion MOx of <70%. Patients with the lowest pre-transfusion MOx had the largest increase in MOx after transfusion. CONCLUSIONS: These preliminary data suggest that MOx may aid in making transfusion decisions when used in combination with Hct.

Lopinavir and atazanavir in pregnancy: comparable infant outcomes, virological efficacies and preterm delivery rates.

OBJECTIVES: The aim of the study was to identify differences in infant outcomes, virological efficacy, and preterm delivery (PTD) outcome between women exposed to lopinavir/ritonavir (LPV/r) and those exposed to atazanavir/ritonavir (ATV/r). METHODS: A retrospective case note review was carried out. The case notes of 493 women who conceived while on LPV/r or ATV/r or initiated LPV/r or ATV/r during pregnancy and who delivered between 1 September 2007 and 30 August 2012 were reviewed. Data collected included demographics, antiretroviral use, HIV markers, and pregnancy and infant outcomes. Infant outcomes, virological efficacies and PTD rates for LPV/r and ATV/r were compared. RESULTS: A total of 306 women received LPV/r (82 conceiving while on the drug and 224 commencing it post-conception) and 187 received ATV/r (96 conceiving while on the drug and 91 commencing it post-conception). Comparing the two protease inhibitors (PIs), viral suppression rates were similar and, in women starting antiretroviral therapy (ART) post-conception, the median times to first undetectable HIV viral load were not significantly different (P = 0.64). PTD rates did not differ by therapy overall (ATV/r, 13%; LPV/r, 14%) or when considering the timing of first exposure (conceiving on ART, P = 0.81; commencing ART in pregnancy, P = 0.08). Poor fetal outcomes were very uncommon. There were two transmissions, giving a mother-to-child transmission (MTCT) rate of 0.4% (95% confidence interval 0.05-1.5%). CONCLUSIONS: Both ART regimens were well tolerated and successful in preventing MTCT. No significant differences in tolerability or in pregnancy or infant outcomes were observed, which supports the provision of a choice of PI in pregnancy.

Fluorescence spectroscopy incorporated in an Optical Biopsy System for the detection of early neoplasia in Barrett's esophagus.

Endoscopic surveillance is recommended for patients with Barrett's esophagus (BE) to detect high-grade intraepithelial neoplasia (HGIN) or early cancer (EC). Early neoplasia is difficult to detect with white light endoscopy and random biopsies are associated with sampling error. Fluorescence spectroscopy has been studied to distinguish non-dysplastic Barrett's epithelium (NDBE) from early neoplasia. The Optical Biopsy System (OBS) uses an optical fiber integrated in a regular biopsy forceps. This allows real-time spectroscopy and ensures spot-on correlation between the spectral signature and corresponding physical biopsy. The OBS may provide an easy-to-use endoscopic tool during BE surveillance. We aimed to develop a tissue-differentiating algorithm and correlate the discriminating properties of the OBS with the constructed algorithm to the endoscopist's assessment of the Barrett's esophagus. In BE patients undergoing endoscopy, areas suspicious for neoplasia and endoscopically non-suspicious areas were investigated with the OBS, followed by a correlating physical biopsy with the optical biopsy forceps. Spectra were correlated to histology and an algorithm was constructed to discriminate between HGIN/EC and NDBE using smoothed linear dicriminant analysis. The constructed classifier was internally cross-validated and correlated to the endoscopist's assessment of the BE segment. A total of 47 patients were included (39 males, age 66 years): 35 BE patients were referred with early neoplasia and 12 patients with NDBE. A total of 245 areas were investigated with following histology: 43 HGIN/EC, 66 low-grade intraepithelial neoplasia, 108 NDBE, 28 gastric or squamous mucosa. Areas with low-grade intraepithelial neoplasia and gastric/squamous mucosa were excluded. The area under the receiver operating characteristic curve of the constructed classifier was 0.78. Sensitivity and specificity for the discrimination between NDBE and HGIN/EC of OBS alone were 81% and 58% respectively. When OBS was combined with the endoscopist's assesssment, sensitivity was 91% and specificity 50%. If this protocol would have guided the decision to obtain biopsies, half of the biopsies would have been avoided, yet 4/43 areas containing HGIN/EC (9%) would have been inadvertently classified as unsuspicious. In this study, the OBS was used to construct an algorithm to discriminate neoplastic from non-neoplastic BE. Moreover, the feasibility of OBS with the constructed algorithm as an adjunctive tool to the endoscopist's assessment during endoscopic BE surveillance was demonstrated. These results should be validated in future studies. In addition, other probe-based spectroscopy techniques may be integrated in this optical biopsy forceps system.

Development of curative therapies for Ewing sarcomas by interdisciplinary cooperative groups in Europe.

Curative therapies for Ewing sarcoma have been developed within cooperative groups. Consecutive clinical trials have systematically assessed the impact and timing of local therapy and the activity of cytotoxic drugs and their combinations. They have led to an increase of long-term disease-free survival to around 70% in patients with localized disease. Translational research in ES remains an area in which interdisciplinary and international cooperation is essential for future progress. This article reviews current state-of-the art therapy, with a focus on trials performed in Europe, and summarizes novel strategies to further advance both the cure rates and quality of survival.

Parameningeal rhabdomyosarcoma in pediatric age: results of a pooled analysis from North American and European cooperative groups.

BACKGROUND: Parameningeal (PM) site is a well-known adverse prognostic factor in children with localized rhabdomyosarcoma (RMS). To identify risk factors associated with outcome at this site, we pooled data from 1105 patients treated in 10 studies conducted by European and North American cooperative groups between 1984 and 2004. PATIENTS AND METHODS: Clinical factors including age, histology, size, invasiveness, nodal involvement, Intergroup Rhabdomyosarcoma Study (IRS) clinical group, site, risk factors for meningeal involvement (MI), study group, and application of radiotherapy (RT) were studied for their impact on event-free and overall survival (EFS and OS). RESULTS: Ten-year EFS and OS were 62.6 and 66.1% for the whole group. Patients without initial RT showed worse survival (10-year OS 40.8% versus 68.5% for RT treated patients). Multivariate analysis focusing on 862 patients who received RT as part of their initial treatment revealed four unfavorable prognostic factors: age <3 or >10 years, signs of MI, unfavorable site, and tumor size. Utilizing these prognostic factors, patients could be classified into different risk groups with 10-year OS ranging between 51.1 and 80.9%. CONCLUSIONS: While, in general, PM localization is regarded as an adverse prognostic factor, the current analysis differentiates those with good prognosis (36% patients with 0-1 risk factor: 10-year OS 80.9%) from high-risk PM patients (28% with 3-4 factors: 10-year OS 51.1%). Furthermore, this analysis reinforces the necessity for RT in PM RMS.

Persistent erythema multiforme associated with Epstein-Barr virus infection.

Erythema multiforme (EM) is a common, self-limiting condition. Recurrent EM is a well-recognised variant, often associated with herpes simplex virus infection. It is frequently managed with prophylactic aciclovir. Anecdotal reports suggest that recurrent EM may be associated with the use of corticosteroids. Persistent EM, however, is a rare variant, with few cases reported in the literature. It has a protracted course often with atypical and inflammatory lesions. It has been associated with occult viral infections, particularly Epstein-Barr Virus (EBV), as well as inflammatory bowel disease and malignancy. We report a case of EM associated with EBV infection.

Contraception in sea-going service personnel.

The right to make an informed choice about contraception should be afforded to every individual serving within the United Kingdom (UK) Armed Forces. This article looks at the responsibilities and approach that healthcare professionals should take within a Primary Care setting, summarises the common contraceptive options available, discusses the associated advantages and disadvantages of each technique, and considers operational factors in a military environment that combine to influence the final contraceptive choice an individual makes. Case Study. A 19-year old Able Rate joined the Royal Navy (RN) and at her joining medical it was noted that she had been on Microgynon™ combined oral contraceptive pill for approximately three years. During this time, her menstrual periods remained light; she never experienced adverse effects, demonstrated good compliance, and was happy to remain on this contraceptive regimen. Over the course of the next eighteen months, she was reviewed by a number of Medical Officers and Civilian Medical Practitioners on a quarterly basis, with Microgynon™ re-prescribed on each occasion. The appropriate Defence Medical Information Capability Programme (DMICP) template was used, with weight, smoking status, compliance and any issues or comments documented accordingly. In December 2010, a discussion regarding long-acting reversible contraception (LARC) was documented for the first time. The patient agreed to give LARC some thought and a review appointment was made for one month. She was subsequently started on the progestogen-only pill Cerazette™. It was noted by the consulting doctor that both the patient's mother and grandmother had a positive history of cerebrovascular events and the combined oral contraceptive pill was discontinued. Upon review at two months, the patient reported that she was content on Cerazette™ and wished to continue with this medication. She was amenorrhoeic, highly compliant, had given up smoking and her weight and blood pressure were stable. However, due to supply issues, it was explained that Cerazette™ was no longer a viable option for her. She had no plans to start a family, and was keen to investigate other contraceptive options. Furthermore, she expressed a particular desire to remain amenorrhoeic, as she was due to deploy overseas in the coming months, and not only wanted to avoid the inconvenience of having her period, but also felt it preferable not to have to take a daily pill when considering the constantly changing time zones. She subsequently had the etonogestrel-releasing subdermal implant Nexplanon™ fitted without complication. She has remained amenorrhoeic throughout and this form of long-acting reversible contraception has particularly suited her busy working role and active lifestyle.

Effect of gonadotropin-releasing hormone or prostaglandin F(2α)-based estrus synchronization programs for first or subsequent artificial insemination in lactating dairy cows.

The objective was to evaluate the effects of GnRH or PGF(2α)-based synchronization and resynchronization programs on fertility in lactating dairy cows. For experiment 1, cows (n=1,521) were presynchronized with 2 injections of PGF given at 36 and 50 DIM and assigned to 1 of 3 protocols: Ovsynch [OVS; n=552; GnRH injection, PGF(2α) injection 7 d later, GnRH injection 56 h later, and timed artificial insemination (TAI) 16 h later] beginning at 14 d after presynchronization (PS), GnRH-GnRH-PGF(2α)-GnRH (GGPG; n=402) treatment with a GnRH injection given 7 d after PS and OVS 7 d later, or PGF(2α)-GnRH-PGF(2α)-GnRH (P7GPG; n=567) treatment with a PGF(2α) injection given 7 d after PS and OVS beginning 7 d later. Experiment 2 cows (n=2,327) were assigned to 1 of 3 resynchronization protocols 7 d before nonpregnancy diagnosis (NPD): GGPG cows (n=458) received a GnRH injection at enrollment and OVS at NPD; P7GPG cows (n=940) received a PGF(2α) injection at NPD and OVS 7 d later; and P11GPG cows (n=929) received a PGF(2α) injection 3 d after NPD and OVS 11 d later. In both experiments, cows were artificially inseminated upon estrus detection (ED). In experiment 1, 52.3% of cows were artificially inseminated upon ED, with GGPG having reduced ED (GGPG=46.8 vs. OVS=50.7 and P7GPG=57.7%). Treatments did not affect overall pregnancy per artificial insemination (P/AI) at 36 and 66 d after AI (OVS=34.1 and 32.3, P7GPG=34.6 and 31.9, and GGPG=31.3 and 28.1%, respectively) or pregnancy loss but cows artificially inseminated upon ED had higher P/AI than cows undergoing TAI (ED cows=37.9 vs. TAI cows=28.8%). Treatment did not affect P/AI for cows artificially inseminated upon ED or TAI at 36 and 66 d after AI (OVS=34.1 and 32.3, P7GPG=34.6 and 31.9, and GGPG=31.3 and 28.1%). Median days in milk at first AI was affected by treatment (P7GPG=59 vs. OVS=68 and GGPG=68 d). In experiment 2, GGPG reduced ED (GGPG=23.3 vs. P7GPG=74.9 and P11GPG=79.6%). Treatment did not affect overall P/AI at 36 and 66 d after AI (GGPG=29.2 and 25.8, P7GPG=28.7 and 26.6, and P11GPG=31.9 and 30.2%) or pregnancy loss. Cows artificially inseminated upon ED had greater P/AI than TAI cows (ED=32.3 and TAI=25.1%). However, treatment did not affect P/AI for cows artificially inseminated upon ED at 36 and 66 d after AI (GGPG=29.6 and 27.3, P7GPG=29.4 and 28.1, and P11GPG=35.7 and 33.7%) or TAI (GGPG=29.1 and 25.3, P7GPG=25.0 and 22.1, and P11GPG=16.9 and 16.9%). Median days between NPD and AI was affected by treatment (GGPG=10 vs. P7GPG=4 and P11GPG=7 d). Prostaglandin-based programs increased ED and reduced interval to first AI and between AI. Gonadotropin-releasing hormone-based programs increased the proportion of TAI cows. Cows artificially inseminated upon ED had increased P/AI compared with TAI cows.

Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions.

The activins (dimers of betaA or betaB subunits, encoded by the genes Inhba and Inhbb, respectively) are TGF-beta superfamily members that have roles in reproduction and development. Whereas mice homozygous for the Inhba-null allele demonstrate disruption of whisker, palate and tooth development, leading to neonatal lethality, homozygous Inhbb-null mice are viable, fertile and have eye defects. To determine if these phenotypes were due to spatiotemporal expression differences of the ligands or disruption of specific ligand-receptor interactions, we replaced the region of Inhba encoding the mature protein with Inhbb, creating the allele Inhbatm2Zuk (hereafter designated InhbaBK). Although the craniofacial phenotypes of the Inhba-null mutation were rescued by the InhbaBK allele, somatic, testicular, genital and hair growth were grossly affected and influenced by the dosage and bioactivity of the allele. Thus, functional compensation within the TGF-beta superfamily can occur if the replacement gene is expressed appropriately. The novel phenotypes in these mice further illustrate the usefulness of insertion strategies for defining protein function.

Screening for methicillin-resistant Staphylococcus aureus (MRSA) in community-recruited injection drug users: are throat swabs necessary?

We examined and described colonization of MRSA in the anterior nares and throat from 184 community-recruited injection drug users. Thirty-seven (20%) were positive for MRSA: most (34, 92%) were carriers in the nares; while only three (8%) were carriers detected by throat swabs alone. The majority (29, 78%) of MRSA isolates were PVL positive.

Clinical parameters in male genital lichen sclerosus: a case series of 329 patients.

BACKGROUND: The dermatological aspects of male genital lichen sclerosus (MGLSc) have not received much prominence in the literature. Sexual morbidity appears under-appreciated, the role of histology is unclear, the relative places of topical medical treatment and circumcision are not established, the prognosis for sexual function, urinary function and penis cancer is uncertain and the pathogenesis has not been specifically studied although autoimmunity (as in women) and HPV infection have been mooted. OBJECTIVE: To illuminate the above by analysing the clinical parameters of a large series of patients with MGLSc. METHODS: A total of 329 patients with a clinical diagnosis of MGLSc were identified retrospectively from a dermatology-centred multidisciplinary setting. Their clinical and histopathological features and outcomes have been abstracted from the records and analysed by simple descriptive statistics. RESULTS: The collation and analysis of clinical data derived from the largest series of men with MGLSc ever studied from a dermatological perspective has been achieved. These data allow the conclusions below to be drawn. CONCLUSIONS: MGLSc is unequivocally a disease of the uncircumcised male; the adult peak is late in the fourth decade; dyspareunia is a common presenting complaint; non-specific histology requires careful interpretation; most men are either cured by topical treatment with ultrapotent steroid (50-60%) or by circumcision (>75%); effective and definitive management appears to abrogate the risk of developing penile squamous cell carcinoma; urinary contact is implicated in the pathogenesis of MGLSc; HPV infection and autoimmunity seem unimportant.