Postweaning growth and feeding behaviour in pigs: effect of heavier hybrid and weaning intact litters in farrowing pens for loose-housed sows.

Abrupt weaning of four-week-old pigs is associated with multiple stressors. Housing pigs in intact litters is a way to reduce the stress associated with moving and mixing of unfamiliar pigs. Furthermore, higher weaning weight may improve pigs' robustness against postweaning stressors. In the present study, it was investigated whether: (1) A heavier pig hybrid, and (2) weaning intact litters in the farrowing pen for loose-housed sows could increase postweaning feeding behaviour and growth. Two sow hybrids (DanBred LY (DB) and Topigs Norsvin TN70 (TN)) and two weaning strategies (the litter stayed intact in the farrowing pen after removing the sow (STAY), or two litters were moved and mixed in conventional weaner pens (MOVE)) were compared in a 2 × 2 factorial design. In total, 57 litters from four batches were included in the study. The TN hybrid sows gave birth to heavier piglets but smaller litter sizes and had more functional teats than DB sows. At weaning, TN pigs were heavier than DB. The number of feed trough (FT) visits on the day before weaning was low in both hybrids. On the day after weaning, the number of FT visits was higher in MOVE compared to STAY, and in TN-STAY compared to DB-STAY. The average daily gain the first two days postweaning was negative in both hybrids and weaning strategies but more pronounced in DB than TN, and STAY tended to lose more weight than MOVE. Over the entire 28-day postweaning period, there was an interaction between hybrid and weaning strategy in that TN-STAY (392 g/d) had higher growth than both TN-MOVE (251 g/d) and DB-MOVE (283 g/d), whereas growth of DB-STAY (316 g/d) was intermediate. In addition, higher weaning weight was associated with a lower number of FT visits and greater weight loss the first two days postweaning but higher growth over the 28-day postweaning period. The results show that abrupt weaning at four weeks of age causes weight loss the first days postweaning despite being housedas intact litters, most likely due to low feed consumption. However, the combination of a heavier pig hybrid and housing intact litters in the farrowing pen postweaning resulted in a higher growth performance over the 28-day postweaning period. In conclusion, pigs that are heavier at weaning reach better growth performance in the longer term, despite having the largest acute postweaning growth depression and fewest FT visits on the day before and after weaning.

Dental procedures in children with or without intellectual disability and autism spectrum disorder in a hospital setting.

BACKGROUND: This population-based cohort study investigated dental procedures in the hospital setting in Western Australian children with or without intellectual disability (ID) and/or autism spectrum disorder (ASD) aged up to 18 years. Considering previously reported disparities in dental disease between Indigenous and non-Indigenous Australian children, this study also investigated the effect of Indigenous status on dental procedures. METHODS: Data on Western Australian live births from 1983 to 2010 from the Midwives Notification System were linked to the Intellectual Disability Exploring Answers database and the Hospital Morbidity Data collection. Primary admissions for relevant dental diagnoses were identified, and treatment procedures for dental hospitalization were investigated. Descriptive statistics and Pearson's chi-squared test of independence were used for analysis. RESULTS: Overall, 76 065 episodes of dental hospitalization were recorded. Amongst children with ID and/or ASD, Indigenous children experienced more extractions and fewer restorations (68.7% and 16.2%) compared to non-Indigenous children (51.5% and 25.9%). After 6 years, extraction occurred less often in children with ID and/or ASD than in those without, where most surgical dental extractions were in the age group of 13-18 years. CONCLUSIONS: This study indicates a need for further improvements in access to dental services and the quality of care provided in hospitals for children with ID/ASD. There is also concern that more vulnerable Indigenous and all disadvantaged children are receiving an inadequate level of dental services resulting in more emergency dental hospitalization and invasive treatment.

JavaCyte, a novel open-source tool for automated quantification of key hallmarks of cardiac structural remodeling.

Many cardiac pathologies involve changes in tissue structure. Conventional analysis of structural features is extremely time-consuming and subject to observer bias. The possibility to determine spatial interrelations between these features is often not fully exploited. We developed a staining protocol and an ImageJ-based tool (JavaCyte) for automated histological analysis of cardiac structure, including quantification of cardiomyocyte size, overall and endomysial fibrosis, spatial patterns of endomysial fibrosis, fibroblast density, capillary density and capillary size. This automated analysis was compared to manual quantification in several well-characterized goat models of atrial fibrillation (AF). In addition, we tested inter-observer variability in atrial biopsies from the CATCH-ME consortium atrial tissue bank, with patients stratified by their cardiovascular risk profile for structural remodeling. We were able to reproduce previous manually derived histological findings in goat models for AF and AV block (AVB) using JavaCyte. Furthermore, strong correlation was found between manual and automated observations for myocyte count (r = 0.94, p < 0.001), myocyte diameter (r = 0.97, p < 0.001), endomysial fibrosis (r = 0.98, p < 0.001) and capillary count (r = 0.95, p < 0.001) in human biopsies. No significant variation between observers was observed (ICC = 0.89, p < 0.001). We developed and validated an open-source tool for high-throughput, automated histological analysis of cardiac tissue properties. JavaCyte was as accurate as manual measurements, with less inter-observer variability and faster throughput.

Study design and outcomes measures: The influence of composite endpoints and other design variables on outcomes in a study of a novel device for stress urinary incontinence.

OBJECTIVES: To perform a post hoc analysis of the outcome data from a phase III study of a novel incontinence therapy for female stress incontinence (SUI) and to understand the pitfalls inherent to performing trials in SUI. METHODS: Results of the SUCCESS Trial, a multicenter, prospective, single-blinded, randomized, sham-controlled study were assessed post hoc for parameters and variables consistent with changes in the symptoms or signs of SUI. Subjects were randomized to either the investigative device (Vesair Balloon) placement or placebo. The efficacy endpoint analysis herein evaluated a composite of both a >50% reduction from baseline on 1-hour provocative pad weight test and a ≥10-point improvement in symptoms on the Incontinence Quality of Life (I-QOL) questionnaire assessed at the three-month study visit. Further analysis was performed utilizing more challenging success criteria for each endpoint and a subset of subjects with more severe baseline symptoms. RESULTS: The three-month composite efficacy endpoint was achieved in 42.1% of treatment group subjects compared with 28.1% of control subjects on an intention-to-treat analysis (P = .046). This difference between groups was not evident when analyzing each component of the composite endpoint separately. These endpoints diverged from endpoints involving improvement in PGI-I score and a 50% reduction of incontinence episode frequency as reported by subjects on a diary. CONCLUSIONS: Individual endpoints may not demonstrate a significant treatment effect as standalone SUI measures but may as components of a composite endpoint. Defining patient selection and outcomes assessments is a critical aspect of study design, experimental flaws, and therapeutic accuracy.

Atherothrombosis and Thromboembolism: Position Paper from the Second Maastricht Consensus Conference on Thrombosis.

Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in)stability; proteomic and metabolomics data are to be added to genetic information. 2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; disease mechanism-based biomarkers need to be identified; experimental systems are needed that incorporate whole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation. 3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin-angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet-fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences. 4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis à vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time. 5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia-reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novel modified activated protein C-based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor.

Validity and reliability of remote dental screening by different oral health professionals using a store-and-forward telehealth model.

Objective This study was conducted to evaluate the validity and reliability of intraoral photographic assessments by different members of a dental team as a means for dental screening in children.Methods The intraoral photographic records of 126 children (2 to 18 years old) were obtained from routine clinical records taken before dental treatment. Intraoral photographs were obtained using a DSLR camera and then uploaded to a cloud-based server using store-and-forward telehealth technology. Images were reviewed by an expert panel to formulate a benchmark screening baseline, to which the screeners' data were compared. The photographic assessments conducted by a mid-level dental practitioner (MLDP) and dentist, were compared to the benchmark expert panel assessment.Results The screeners' assessments by means of intraoral photography, when compared to the expert panel assessment had a sensitivity value of 82-89% and specificity value of 97%. The inter-examiner agreement between the expert panel assessment and photographic method (assessed by a dentist and MLDP), was almost perfect, with a kappa score ranging from 0.82 to 0.88. The mean DFT/dft score for the children as determined by the expert panel's review and photographic assessment ranging from 5.41 to 5.79, with mean scores between the two assessment methods not significantly different (P = 0.746).Conclusion Our results suggested that oral health professionals (other than dentists) have the potential to screen for caries from intraoral photographs with the same diagnostic accuracy and reliability as dentists. This strategy has implications for supporting the use of MLDPs such as dental therapists or hygienists to screen for oral disease using telehealth.

Developmental and Regulatory Functions of Na(+) Channel Non-pore-forming ß Subunits.

Voltage-gated Na(+) channels (VGSCs) isolated from mammalian neurons are heterotrimeric complexes containing one pore-forming α subunit and two non-pore-forming ß subunits. In excitable cells, VGSCs are responsible for the initiation of action potentials. VGSC ß subunits are type I topology glycoproteins, containing an extracellular amino-terminal immunoglobulin (Ig) domain with homology to many neural cell adhesion molecules (CAMs), a single transmembrane segment, and an intracellular carboxyl-terminal domain. VGSC ß subunits are encoded by a gene family that is distinct from the α subunits. While α subunits are expressed in prokaryotes, ß subunit orthologs did not arise until after the emergence of vertebrates. ß subunits regulate the cell surface expression, subcellular localization, and gating properties of their associated α subunits. In addition, like many other Ig-CAMs, ß subunits are involved in cell migration, neurite outgrowth, and axon pathfinding and may function in these roles in the absence of associated α subunits. In sum, these multifunctional proteins are critical for both channel regulation and central nervous system development.

Mesh Excision: Is Total Mesh Excision Necessary?

Nearly 29% of women will undergo a secondary, repeat operation for pelvic organ prolapse (POP) symptom recurrence following a primary repair, as reported by Abbott et al. (Am J Obstet Gynecol 210:163.e1-163.e1, 2014). In efforts to decrease the rates of failure, graft materials have been utilized to augment transvaginal repairs. Following the success of using polypropylene mesh (PPM) for stress urinary incontinence (SUI), the use of PPM in the transvaginal repair of POP increased. However, in recent years, significant concerns have been raised about the safety of PPM mesh. Complications, some specific to mesh, such as exposures, erosion, dyspareunia, and pelvic pain, have been reported with increased frequency. In the current literature, there is not substantive evidence to suggest that PPM has intrinsic properties that warrant total mesh removal in the absence of complications. There are a number of complications that can occur after transvaginal mesh placement that do warrant surgical intervention after failure of conservative therapy. In aggregate, there are no high-quality controlled studies that clearly demonstrate that total mesh removal is consistently more likely to achieve pain reduction. In the cases of obstruction and erosion, it seems clear that definitive removal of the offending mesh is associated with resolution of symptoms in the majority of cases and reasonable practice. There are a number of complications that can occur with removal of mesh, and patients should be informed of this as they formulate a choice of treatment. We will review these considerations as we examine the clinical question of whether total versus partial removal of mesh is necessary for the resolution of complications following transvaginal mesh placement.

Surgical repair of pelvic organ prolapse in elderly patients.

PURPOSE OF REVIEW: Epidemiologic data suggests that our population greater than 65 years of age will nearly double. In addition, the incidence of women undergoing surgery for pelvic organ prolapse will rise. Chronologic age does not preclude a woman from undergoing a reconstructive procedure, yet the preoperative assessment should be approached most judiciously with great care to insure patient is maximally medically prepared for surgery. RECENT FINDINGS: Surgical procedures in this review include: the abdominal sacral colpopexy, anterior repair, posterior repair, sacrospinous ligament fixation, uterosacral suspension, and iliococcygeus fixation. The advent of robotic surgery has decreased the perioperative morbidity of several of these procedures. However, the risk of more severe complications does appear higher following robotic procedures, when compared with vaginal procedures. SUMMARY: Intuitively, one would surmise that there is a point where vaginal surgery should be considered as the primary procedure based on age, risk and durability of the surgery - unfortunately that age is not clear. Thus, the proper selection of prevalence of organ prolapse surgery can only be done after careful discussion with the patient and including the patient in the selection process as much as possible.

Birthplace and esophageal cancer incidence patterns among Asian-Americans.

The incidence of esophageal adenocarcinoma in the United States has risen rapidly over the last 30 years, whereas the incidence of esophageal squamous cell carcinoma has fallen dramatically. In contrast, parts of Asia have extremely high rates of squamous cell carcinoma, but virtually no adenocarcinoma. Within the United States, Asian-Americans as a whole, have low rates of esophageal adenocarcinoma and higher rates of squamous cell carcinoma. It is unclear what the patterns are for those Asians born in the United States. The relative influence of ethnicity and environment on the incidence of esophageal cancer in this population is unknown. We identified all cases of esophageal adenocarcinoma and squamous cell carcinoma from the California Cancer Registry 1988-2004, including 955 cases among 6 different Asian ethnicities. Time trends were examined using Joinpoint software to calculate the annual percentage changes in regression models. Rates of esophageal squamous cell carcinoma varied substantially among different Asian ethnic groups, but squamous cell carcinoma was much more common than adenocarcinoma in both foreign-born and US-born Asian-Americans. Rates of squamous cell carcinoma were slightly higher among US-born Asian men (4.0 per 100,000) compared with foreign-born Asian men (3.2 per 100,000) and White men (2.2 per 100,000), P = 0.03. Rates of adenocarcinoma were also slighter higher among US-born Asian men (1.2 per 100,000) compared with foreign-born Asian men (0.7 per 100,000), P = 0.01. Rates of squamous cell carcinoma decreased for both US-born and foreign-born Asians during this period, whereas adenocarcinoma remained low and stable. These results provide better insight into the genetic and environmental factors affecting the changing incidence of esophageal cancer histologies in the United States and Asia.

Central venous catheters and upper extremity deep vein thrombosis in medical inpatients: the Medical Inpatients and Thrombosis (MITH) Study.

BACKGROUND: Upper extremity deep vein thrombosis (UEDVT) is an increasingly recognized complication in medical inpatients, with few data available regarding the incidence, risk factors and association with central venous catheter (CVC) use. METHODS: Between 2002 and 2009 all cases of hospital-acquired venous thromboembolism (VTE) at a university hospital were frequency matched 1 : 2 to non-cases without VTE by admission year and medical service. Records were abstracted to identify, characterize and assess risk factors for UEDVT. Weighted logistic regression was used to calculate odds ratios (ORs) for UEDVT associated with use of a CVC, adjusting for known VTE risk factors. RESULTS: Two hundred and ninety-nine cases of VTE complicated 64 034 admissions to medical services (4.6 per 1000 admissions). UEDVT constituted 51% (91/180) of all deep vein thrombosis (DVT), for an incidence of 1.4 per 1000 admissions (95% confidence interval [CI], 0.8-1.7). There were 247 CVCs placed per 1000 admissions (95% CI, 203-292). The use of a CVC was associated with a 14.0-fold increased risk of UEDVT (95% CI, 5.9-33.2), but was not associated with a significantly increased risk of PE (OR, 1.3; 95% CI, 0.8-2.1). Peripherally inserted central catheters had a higher OR for UEDVT (OR, 13.0; 95% CI, 6.1-27.6) than centrally inserted central venous catheters (CICC) (OR, 3.4; 95% CI, 1.7-6.8). CONCLUSION: UEDVT is a relevant complication affecting medical inpatients, accounting for half of hospital-acquired DVTs. Use of CVCs was strongly associated with risk of UEDVT.

AUA/SUFU adult urodynamics guideline: a clinical review.

The American Urological Association/Society of Urodynamics Female Pelvic Medicine and Urogenital Reconstruction Adult Urodynamics Guideline was published with the intent of guiding the clinician in the role of urodynamics in the evaluation and management of complex lower urinary tract conditions. This article examines each guideline statement and attempts to provide clinical context for each statement. Key points are emphasized in the form of clinical case scenarios, which demonstrate application of the principles stressed in this guideline. It is hoped the reader will have a better clinical frame of reference relative to each statement in these guidelines.

Phase 2 trial of intravenously administered plerixafor for stem cell mobilization in patients with multiple myeloma following lenalidomide-based initial therapy.

Initial therapy of multiple myeloma with lenalidomide-based regimens can compromise stem cell collection, which can be overcome with the addition of plerixafor. Plerixafor is typically given subcutaneously (SQ), with collection ∼11 h later for maximum yield. Intravenous administration may allow more rapid and predictable mobilization. This trial was designed to assess the efficacy and feasibility of IV plerixafor in patients receiving initial therapy with a lenalidomide-based regimen. Patients received G-CSF at 10 µg/kg/day for 4 days followed by IV plerixafor at 0.24 mg/kg/dose starting on day 5; plerixafor was administered early in the morning with apheresis 4-5 h later. Thirty-eight (97%) patients collected at least 3 × 10(6) CD34+ cells/kg within 2 days of apheresis. The median CD34+ cells/kg after 1 day of collection was 3.9 × 10(6) (range: 0.7-9.2) and after 2 days of collection was 6.99 × 10(6) (range: 1.1-16.5). There were no grade 3 or 4 non-hematological adverse events, and one patient experienced grade 4 thrombocytopenia. The most common adverse events were nausea, diarrhea and abdominal bloating. IV plerixafor is an effective strategy for mobilization with low failure rate and is well tolerated. It offers flexibility with a schedule of early-morning infusion followed by apheresis later in the day.

Urodynamics: examining the current role of UDS testing. What is the role of urodynamic testing in light of recent AUA urodynamics and overactive bladder guidelines and the VALUE study?

Urodynamics testing is a diagnostic assessment of the lower urinary tract system composed of multiple tests to obtain physiologic data regarding lower urinary tract function (detrusor and outlet) during storage and emptying. The necessity of urodynamics has been both supported and challenged in various urologic conditions such as urinary incontinence, neurogenic bladder, lower urinary tract symptoms, and bladder outlet obstruction. This review discusses the most recent studies with regards to the utility of urodynamics in current practice, highlighting the recent American Urologic Association Adult Urodynamics and Overactive Bladder Guidelines and the Value of Urodynamic Evaluation study.

Dermal and conjunctival melanocytic proliferations in diffuse uveal melanocytic proliferation.

AIM: The goal of this case report is to describe the dermatologic and conjunctival findings in a case of bilateral diffuse uveal melanocytic proliferation (BDUMP), a paraneoplastic syndrome usually associated with gynecologic cancers. There is little information about other dermatologic melanocytic findings in these patients. METHODS: Histologic and fluorescent in situ hybridization (FISH) analysis of three separate skin biopsies, one of which was separated by 21 months from the others, were performed in a 71-year-old patient with BDUMP to assess for histologic and chromosomal abnormality. Conjunctival histologic evaluation was also done. RESULTS: Dermal melanocytic proliferation was seen in each specimen. The cells were spindle type with mitotic activity. FISH analysis showed a normal copy of chromosomes. The conjunctival sample also showed normal FISH analysis. CONCLUSION: BDUMP is associated with multifocal dermal and conjunctival melanocytic proliferation.

Size of urogenital hiatus as a potential risk factor for emptying disorders after pelvic prolapse repair.

PURPOSE: We correlated urogenital hiatus size and levator ani contraction strength with early postoperative emptying disorders. We also determined whether postoperative emptying disorders could be predicted before anti-incontinence procedures and pelvic organ prolapse repair. MATERIALS AND METHODS: We retrospectively reviewed the charts of 225 consecutive patients after surgery for pelvic organ prolapse and/or stress urinary incontinence. Urogenital hiatus size was evaluated using pelvic organ prolapse quantification. Levator contraction strength was determined by the Oxford 0 to 5 classification scale. Emptying disorders were defined as post-void residual urine volume greater than 100 ml 48 hours postoperatively and/or discharge home with a Foley catheter or on intermittent self-catheterization. RESULTS: Median patient age, post-void residual urine volume and urogenital hiatus size were significantly related to levator contraction strength (each p <0.05). Univariate logistic regression analysis revealed a significant association of urogenital hiatus size (p = 0.001), post-void residual urine volume (p = 0.005) and levator contraction strength (p = 0.001) with emptying disorder status. Multivariate logistic regression analysis showed that levator contraction strength (p = 0.001) and post-void residual urine (p = 0.01) were independent predictors of emptying disorders. CONCLUSIONS: A wide urogenital hiatus, decreased levator ani contraction strength, increasing age and increased post-void residual urine correlated with an increased chance of early postoperative emptying disorders. The most independent predictors of early emptying disorders were decreased levator contraction strength and increased post-void residual urine.