The association between time-series milk ß-hydroxybutyrate dynamics and early reproductive performance of dairy cows.

The DeLaval Herd Navigator is an on-farm sensor system that measures on a frequent basis milk progesterone (P4) and ß-hydroxybutyrate (BHB) in individual cows to closely monitor reproductive performance and energy balance. This information provides the opportunity to investigate the dynamics of BHB measured in milk (mBHB) and study the association between mBHB and early reproductive performance. The objectives of the study were (1) to describe mBHB dynamics within the first 20 d in milk (DIM), and (2) to evaluate the association between mBHB dynamics and early reproductive performance at cow-level. Two-year time-series data from 4,133 dairy cows in 38 Dutch dairy farms were available for analysis. Data included information on mBHB, daily milk yield and the indicators of early reproductive performance, days from calving to resumption of cyclicity, days from calving to first estrus, and days from calving to first insemination. The following mBHB dynamic parameters were defined based on the first 20 DIM for each individual cow: average mBHB (AvgBHB), DIM when mBHB was for the first time ≥80 µmol/L (OnsetKeto), the total number of consecutive days a cow had mBHB concentration ≥80 µmol/L, and the number of measurements mBHB concentration was ≥80 µmol/L. Three Cox proportional hazard regression models with random herd effect were developed to evaluate the association between cow level mBHB dynamics and days from calving to resumption of cyclicity, first estrus, and first insemination. Results showed that the mean AvgBHB within 20 DIM among all cows was 73 µmol/L. The mean OnsetKeto within 20 DIM, was 8 DIM. Among all cows having hyperketolactia, 55.8% (1,350/2,419) had OnsetKeto in the first week of lactation. In total, 41.5% (1,714/4,133) of the cows did not have OnsetKeto in the first 20 DIM. An early onset of hyperketolactia was associated with delayed fertility events. Cows with higher AvgBHB have a prolonged time interval from calving to resumption of cyclicity and first estrus. Information on mBHB dynamics and the association with early reproductive performance provides insights that might be helpful to improve reproductive performance of individual dairy cows.

Time profiles of energy balance in dairy cows in association with metabolic status, inflammatory status, and disease.

The early lactation period in dairy cows is characterized by complex interactions among energy balance (EB), disease, and alterations in metabolic and inflammatory status. The objective of this study was to cluster cows based on EB time profiles in early lactation and investigate the association between EB clusters and inflammatory status, metabolic status, oxidative stress, and disease. Holstein-Friesian dairy cows (n = 153) were selected and monitored for disease treatments during wk 1 to 6 in lactation. Weekly EB was calculated based on energy intake and energy requirements for maintenance and milk yield in wk 1 to 6 in lactation. Weekly plasma samples were analyzed for metabolic variables in wk 1 to 6, and inflammatory and oxidative stress variables in wk 1, 2, and 4 in lactation. Liver activity index (LAI) was computed from plasma albumin, cholesterol, and retino-binding protein concentration. First, cows were clustered based on time profiles of EB, resulting in 4 clusters (SP: stable positive; MN: mild negative; IN: intermediate negative; SN: severe negative). Cows in the SN cluster had higher plasma nonesterified fatty acids and ß-hydroxybutyrate concentrations, compared with cows in the SP cluster, with the MN and IN cluster being intermediate. Cows in the SN cluster had a higher milk yield, lower dry matter intake in wk 1, lower insulin concentration compared with cows in the SP cluster, and lower glucose and IGF-1 concentration compared with cows in the SP and MN clusters. Energy balance clusters were not related with plasma haptoglobin, cholesterol, albumin, paraoxonase, and liver activity index (LAI). Second, cows were grouped based on health status [IHP: cows with treatment for inflammatory health problem (endometritis, fever, clinical mastitis, vaginal discharge or retained placenta); OHP: cows with no IHP but treatment for other health problem (milk fever, cystic ovaries, claw, and leg problems, rumen and intestine problems or other diseases); NHP: cows with no treatments, in the first 6 weeks after calving]. Energy balance was not different among health status groups. The IHP cows had lower nonesterified fatty acids and greater insulin concentration in plasma compared with OHP. The IHP cows had lower plasma albumin concentration, lower LAI and higher haptoglobin concentration compared with OHP and NHP. Overall, EB time profiles were associated with the metabolic status of dairy cows in early lactation, but were only limitedly related with markers of inflammation and oxidative stress status. Inflammatory and metabolic status were related to disease events in early lactation and caused prolonged effects on liver metabolism.

Increased efficacy of dual proinflammatory cytokine blockade on acute GVHD while maintaining GVT effects.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potential curative option for treating a variety of hematologic diseases, but acute and chronic graft-versus-host disease (GVHD) remain major barriers limiting efficacy. Acute gut GVHD occurs with marked increases in proinflammatory cytokines (including TNF and IL-6), which we recently demonstrated was exacerbated in obesity resulting in severe gastrointestinal pathology. Given the pleiotropic and overlapping effects of these 2 cytokines, we assessed the impact of dual TNF and IL-6R blockade on GVHD as well as graft-versus tumor (GVT) effects in different mouse GVHD models. Early administration of combined blockade resulted in greater protection and survival from acute gut GVHD compared with single blockade regimens and even development of later chronic skin GVHD. Importantly, double cytokine blockade preserved GVT effects reinforcing that GVT and GVHD can be delineated and may result in greater efficacy in allo-HSCT.

Effect of discharge opioid on persistent postoperative opioid use: a retrospective cohort study comparing tapentadol with oxycodone.

Opioid harm can vary by opioid type. This observational study examined the effect of opioid type (oxycodone vs. tapentadol) on rates of persistent postoperative opioid use ('persistence'). We linked hospital and community pharmacy data for surgical patients who were dispensed discharge opioids between 1 January 2016 and 30 September 2021. Patients were grouped by opioid experience ('opioid-naive' having received no opioids in the 3 months before discharge) and formulation of discharge opioid (immediate release only or modified release ± immediate release). Mixed-effects logistic regression models predicted persistence (continued use of any opioid at 90 days after discharge), controlling for key persistence risk factors. Of the 122,836 patients, 2.31% opioid-naive and 27.24% opioid-experienced patients met the criteria for persistence. For opioid-naive patients receiving immediate release opioids, there was no significant effect of opioid type. Tapentadol modified release was associated with significantly lower odds of persistence compared with oxycodone modified release, OR (95%CI) 0.81 (0.69-0.94) for opioid-naive patients and 0.81 (0.71-0.93) for opioid-experienced patients. Among patients who underwent orthopaedic surgery (n = 19,832), regardless of opioid experience or opioid formulation, the odds of persistence were significantly lower for those who received tapentadol compared with oxycodone. This was one of the largest and most extensive studies of persistent postoperative opioid use, and the first that specifically examined persistence with tapentadol. There appeared to be lower odds of persistence for tapentadol compared with oxycodone among key subgroups, including patients prescribed modified release opioids and those undergoing orthopaedic surgery.

Prevalence of extended-spectrum and AmpC ß-lactamase-producing Escherichia coli in young calves on Dutch dairy farms.

In young calves on dairy farms the animal prevalence of extended-spectrum and AmpC ß-lactamase-producing Escherichia coli (ESBL/AmpC-EC) is significantly higher compared with the animal prevalence in young stock and dairy cows. Hitherto it was unknown at what age antimicrobial resistant bacteria appear for the first time in the gut of calves on dairy farms, and how long these infections persist. The aim of this study was to examine the prevalence of ESBL/AmpC-EC, the number of excreted ESBL/AmpC-EC (in cfu/g of feces), as well as the ESBL/AmpC genotypes in young dairy calves (0-21 d of age) and the variation of these parameters between calves of different ages. Next to this, the course of shedding ESBL/AmpC-EC during the first year in dairy calves was studied. In a cross-sectional study, fecal samples from 748 calves, from 0 to 88 d of age, on 188 Dutch dairy farms were collected. The prevalence of calves testing positive for ESBL/AmpC-EC in a phenotypic assay was determined for different age categories (per 2 d of age). Positive samples were subjected to a semiquantitative test to determine the numbers of ESBL/AmpC-EC per gram of feces and for a selection of ESBL/AmpC-EC isolates the ESBL/AmpC genotype was determined. Ten of the 188 farms were selected for a longitudinal study based on the presence of at least 1 female calf with ESBL/Amp-EC in the cross-sectional study. These farms were additionally visited 3 times with a 4-mo interval. All calves that were sampled in the cross-sectional study were, if still present, resampled during the follow-up visits. Results show that from the day of birth ESBL/AmpC-EC can be present in the gut of calves. The phenotypic prevalence of ESBL/AmpC-EC was 33.3% in 0- to 21-d-old calves and 28.4% in 22- to 88-d-old calves. The prevalence of ESBL/AmpC-EC positive calves varied per age category among calves up to 21 d of age: significant increases and decreases at an early age were shown. Results of the longitudinal study show that after 4, 8, and 12 mo the prevalence of ESBL/AmpC-EC positive calves dropped to 3.8% (2/53), 5.8% (3/52), and 2.0% (1/49), respectively. This indicates that early gut colonization in young calves with ESBL/AmpC-EC is transient and does not lead to long-term shedding of these bacteria.

Inability to work following COVID-19 vaccination-a relevant aspect for future booster vaccinations.

OBJECTIVES: COVID-19 vaccination is a key prevention strategy to reduce the spread and severity of SARS-CoV-2 infections. However, vaccine-related inability to work among healthcare workers (HCWs) could overstrain healthcare systems. STUDY DESIGN: The study presented was conducted as part of the prospective CoVacSer cohort study. METHODS: This study examined sick leave and intake of pro re nata medication after the first, second, and third COVID-19 vaccination in HCWs. Data were collected by using an electronic questionnaire. RESULTS: Among 1704 HCWs enrolled, 595 (34.9%) HCWs were on sick leave following at least one COVID-19 vaccination, leading to a total number of 1550 sick days. Both the absolute sick days and the rate of HCWs on sick leave significantly increased with each subsequent vaccination. Comparing BNT162b2mRNA and mRNA-1273, the difference in sick leave was not significant after the second dose, but mRNA-1273 induced a significantly longer and more frequent sick leave after the third. CONCLUSION: In the light of further COVID-19 infection waves and booster vaccinations, there is a risk of additional staff shortages due to postvaccination inability to work, which could negatively impact the already strained healthcare system and jeopardise patient care. These findings will aid further vaccination campaigns to minimise the impact of staff absences on the healthcare system.

Decreased cortical bone density and mechanical strength with associated elevated bone turnover markers at peri-pubertal peak height velocity: a cross-sectional and longitudinal cohort study of 396 girls with adolescent idiopathic scoliosis.

Decreased cortical bone density and bone strength at peak height velocity (PHV) were noted in girls with adolescent idiopathic scoliosis (AIS). These findings could provide the link to the previously reported observation that low bone mineral density (BMD) could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS. INTRODUCTION: As part of the studies related to aetiopathogenesis of AIS, we assessed bone qualities, bone mechanical strength and bone turnover markers (BTMs) focusing at the peri-pubertal period and PHV in AIS girls. METHODS: 396 AIS girls in two separate cohorts were studied. Skeletal maturity was assessed using the validated thumb ossification composite index (TOCI). Bone qualities and strength were evaluated with high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA). RESULTS: Cohort-A included 179 girls (11.95 ± 0.95 years old). Girls at TOCI-4 had numerically the highest height velocity (0.71 ± 0.24 cm/month) corresponding to the PHV. Subjects at TOCI-4 had lower cortical volumetric BMD (672.36 ± 39.07 mg/mm3), cortical thickness (0.68 ± 0.08 mm) and apparent modulus (1601.54 ± 243.75 N/mm2) than: (a) those at TOCI-1-3 (724.99 ± 32.09 mg/mm3 (p < 0.001), 0.79 ± 0.11 mm (p < 0.001) and 1910.88 ± 374.75 N/mm2 (p < 0.001), respectively) and (b) those at TOCI-8 (732.28 ± 53.75 mg/mm3 (p < 0.001), 0.84 ± 0.14 mm (p < 0.001), 1889.11 ± 419.37 N/mm2 (p < 0.001), respectively). Cohort-B included 217 girls (12.22 ± 0.89 years old). Subjects at TOCI-4 had higher levels of C-terminal telopeptide of type 1 collagen (1524.70 ± 271.10 pg/L) and procollagen type 1 N-terminal propeptide (941.12 ± 161.39 µg/L) than those at TOCI-8 (845.71 ± 478.55 pg/L (p < 0.001) and 370.08 ± 197.04 µg/L (p < 0.001), respectively). CONCLUSION: AIS girls had decreased cortical bone density and bone mechanical strength with elevated BTMs at PHV. Coupling of PHV with decreased cortical and FEA parameters could provide the link to the previously reported observation that low BMD could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS.

Latent profile analyses of disordered eating behaviors and nonsuicidal self-injury among Vietnamese adolescents.

OBJECTIVE: Comorbidity of disordered eating (DE) behaviors and nonsuicidal self-injury (NSSI) is linked to increased functional impairment. The present study identified subtypes of DE and NSSI comorbidity in a non-Western, low- and middle-income country where there has been particularly little research in this area. METHOD: Latent profile analyses (LPA) were conducted to identify patterns of subgroup comorbidity in self-reported DE behaviors and NSSI behaviors, in a sample of Vietnamese high-school students (N = 1451, 51% female). Parallel-process LPA was used to predict NSSI subgroup membership from DE subgroup membership. RESULTS: A seven-class LPA model was identified for DE: (1) Low frequencies of all DE behaviors; (2) Frequent levels of all DE behaviors; (3) Frequent fasting and purging behaviors; (4) Frequent binge eating only; (5) Moderate binge eating; (6) Moderate fasting and purging behaviors; (7) Exercise and fasting. A two-class (high versus low) model was identified for NSSI. Odds of membership in the high-NSSI class were significantly increased for all DE classes except the class characterized by moderate binge eating. Odds of belonging to the high-NSSI class were highest for those in DE classes involving purging behaviors. Males predominated in classes characterized by high behavior dysregulation. DISCUSSION: DE and NSSI represent important clinical concerns among Vietnamese youth in urban contexts, and males may show particular vulnerability for certain risk behaviors. The association of classes of DE behaviors to NSSI was particularly strong for classes that involved purging, highlighting the importance of this specific behavior for understanding comorbidity of DE and NSSI. PUBLIC SIGNIFICANCE: Disordered eating and nonsuicidal self-injury (NSSI; hurting oneself without intending to die) commonly co-occur. There has been less research on disordered eating and NSSI among individuals from non-Western or low/middle-income countries. We examined patterns of these behaviors in a school-based sample of Vietnamese adolescents. We found that patterns of disordered eating distinguished by purging showed particular links to NSSI, which could have implications for screening and treatment.

Effect of selective dry cow treatment on udder health and antimicrobial usage on Dutch dairy farms.

Since 2013, selective dry cow treatment (SDCT) has been the standard approach in the Netherlands where farmers select cows for the use of antimicrobials at drying-off. Shortly after its introduction, antimicrobial usage decreased significantly, and no significant association was found between the level of SDCT and clinical mastitis (CM). Obviously, at that time long-term associations could not be evaluated. This study aimed to provide insight into the methods and level of implementation of SDCT on Dutch dairy farms with a conventional milking system (CMS) or an automatic milking system (AMS) in 2016 and 2017, several years after the implementation of SDCT. Udder health and antimicrobial use were also assessed. For this study, 262 farmers recorded dry cow treatments as well as all CM cases in the period from May 1, 2016, until April 30, 2017. Additionally, somatic cell count (SCC) data on cow and herd level, treatment data on herd level and questionnaire results on udder health management were collected. Data were analyzed using descriptive statistics with differences between milking systems being evaluated using nonparametric univariable statistics. In the study period, SDCT was applied on almost all (98.8%) of the participating dairy farms. The main reason for applying antimicrobials at drying-off was either the SCC history during the complete previous lactation or the SCC at the last milk recording before drying-off. The median percentage of cows treated with antimicrobials was 48.5%. The average incidence rate of CM was 27.3 cases per 100 cows per year. From all CM cases that were registered per herd, on average 32.8% were scored as mild, 42.2% as moderate, and 25.0% as severe CM. The mean bulk tank SCC of the herds was 168,989 cells/mL. A cow was considered to have subclinical mastitis (SCM) if individual SCC was ≥150,000 cells/mL for primiparous and ≥250,000 cells/mL for multiparous cows. Passing these threshold values after 2 earlier low SCC values was considered a new case of SCM. The mean incidence rate of SCM in these herds was 62.5 cases per 100 cows per year. Bulk tank SCC and the incidence rate of SCM on farms with a CMS were statistically lower than on farms with an AMS, whereas the incidence rate of CM did not significantly differ between both groups of farms. The AMS farms had more cows per herd treated with antimicrobials at drying-off and a larger proportion of severe CM cases than did CMS farms. It is unknown whether the differences are due to the milking system or to other differences between both types of farms. This study showed the level of adoption of SDCT, udder health, and antimicrobial usage parameters several years after the ban on the preventive use of antimicrobials in animal husbandry. It found that udder health parameters did not differ from those found in Dutch studies before and around the time of implementing SDCT, whereas SDCT was widely applied on Dutch dairy farms during the study period. Therefore, it was concluded that Dutch dairy farmers were able to handle the changed policy of antimicrobial use at drying-off while maintaining indicators of a good udder health.

Simulations of Proposed Mechanisms of FtsZ-Driven Cell Constriction.

To divide, bacteria must constrict their membranes against significant force from turgor pressure. A tubulin homolog, FtsZ, is thought to drive constriction, but how FtsZ filaments might generate constrictive force in the absence of motor proteins is not well understood. There are two predominant models in the field. In one, FtsZ filaments overlap to form complete rings around the circumference of the cell, and attractive forces cause filaments to slide past each other to maximize lateral contact. In the other, filaments exert force on the membrane by a GTP-hydrolysis-induced switch in conformation from straight to bent. Here, we developed software, ZCONSTRICT, for quantitative three-dimensional (3D) simulations of Gram-negative bacterial cell division to test these two models and identify critical conditions required for them to work. We find that the avidity of any kind of lateral interactions quickly halts the sliding of filaments, so a mechanism such as depolymerization or treadmilling is required to sustain constriction by filament sliding. For filament bending, we find that a mechanism such as the presence of a rigid linker is required to constrain bending to within the division plane and maintain the distance observed in vivo between the filaments and the membrane. Of these two models, only the filament bending model is consistent with our lab's recent observation of constriction associated with a single, short FtsZ filament.IMPORTANCE FtsZ is thought to generate constrictive force to divide the cell, possibly via one of two predominant models in the field. In one, FtsZ filaments overlap to form complete rings which constrict as filaments slide past each other to maximize lateral contact. In the other, filaments exert force on the membrane by switching conformation from straight to bent. Here, we developed software, ZCONSTRICT, for three-dimensional (3D) simulations to test these two models. We find that a mechanism such as depolymerization or treadmilling are required to sustain constriction by filament sliding. For filament bending, we find that a mechanism that constrains bending to within the division plane is required to maintain the distance observed in vivo between the filaments and the membrane.

Association of serum 25(OH)Vit-D levels with risk of pediatric fractures: a systematic review and meta-analysis.

The association between the risk of fractures and suboptimal vitamin D (Vit-D) status remains controversial in children. This meta-analysis suggested that serum 25(OH)Vit-D levels were lower in pediatric cases with fractures. 25-hydroxyvitamin D (25(OH)Vit-D) levels less than 50 nmol/L were associated with increased fracture risk in children. INTRODUCTION: This study aimed to assess the association between serum 25(OH)Vit-D and the risk of fractures in children, and to explore the sources of heterogeneity and investigate their impact on results. METHODS: Systematic review and meta-analysis were conducted for observational studies comparing serum 25(OH)Vit-D levels between fracture and non-fracture pediatric cases. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Analysis on 17 case-control and 6 cross-sectional studies (2929 fracture cases and 5000 controls) suggested that 25(OH)Vit-D was lower in fracture cases than in controls (pooled mean difference (MD) = - 3.51 nmol/L; 95% confidence interval (CI): - 5.60 to - 1.42) with a heterogeneity (I2) of 73.9%. The sensitivity analysis which merged the case-control studies that had a NOS score ≥ 4 showed a pooled MD of - 4.35 nmol/L (95% CI: - 6.64 to - 2.06) with a heterogeneity (I2) of 35.9%. Pooled odds ratio of fracture in subjects with 25(OH)Vit-D ≤ 50 nmol/L compared to subjects with 25(OH)Vit-D > 50 nmol/L was 1.29 (95% CI: 1.10 to 1.53; I2 < 1%). CONCLUSION: This study indicated that serum 25(OH)Vit-D levels were lower in pediatric patients with fractures. 25(OH)Vit-D ≤ 50 nmol/L was associated with increased fracture risk in children.

Polytobacco product use among current cigarette smokers in Hong Kong, China: results from population surveys (2015-17).

BACKGROUND: Polytobacco product use is increasingly popular, but little is known about the prevalence, trend, and factors of such use particularly in non-western countries. METHOD: A representative sample of 1139 current cigarette smokers aged 15+ (84.1% male) were telephone interviewed in Tobacco Control Policy-related Surveys in 2015-2017. Information collected included poly-tobacco use (PTU), smoking and socio-demographic characteristics. Associations of current PTU with related factors were analyzed using logistic regression with adjustment for confounders. Prevalence was weighted by age and sex of current cigarette users in the general population. RESULTS: Eighty-four point one percent (95% CI 81.4-86.6%) were exclusive cigarette smokers. Fifteen point nine percent (13.4-18.6%) were current polytobacco product users, 12.3% (10.2-14.8%) used one tobacco product and 2.52% (1.59-3.97%) used two tobacco products in addition to cigarette. Cigarette use with cigar was more common (6.28%, 4.75-8.27%), and the least used product with cigarette was e-cigarette (1.05%, 0.44-2.50%). The changes in overall prevalence of PTU by number of products use varied in 3 years. Current PTU was associated with being male (AOR 2.01, 95% CI 1.12-3.61), younger age (AORs range from 1.34-4.65, P for trend < .001) and less ready to quit (2.08, 1.09-3.97). CONCLUSIONS: Prevalence of PTU increased slowly by year, one tobacco product use with cigarette was more common. The most used tobacco product with cigarette was cigar. Being male, younger and less ready to quit were associated with current PTU.

Structure of the fission yeast actomyosin ring during constriction.

Cell division in many eukaryotes is driven by a ring containing actin and myosin. While much is known about the main proteins involved, the precise arrangement of actin filaments within the contractile machinery, and how force is transmitted to the membrane, remains unclear. Here we use cryosectioning and cryofocused ion beam milling to gain access to cryopreserved actomyosin rings in Schizosaccharomyces pombe for direct 3D imaging by electron cryotomography. Our results show that straight, overlapping actin filaments, running nearly parallel to each other and to the membrane, form a loose bundle of ∼150 nm in diameter that "saddles" the inward-bending membrane at the leading edge of the division septum. The filaments do not make direct contact with the membrane. Our analysis of the actin filaments reveals the variability in filament number, nearest-neighbor distances between filaments within the bundle, their distance from the membrane, and angular distribution with respect to the membrane.

Regularly fluctuating somatic cell count pattern in dairy herds.

Online somatic cell count (SCC) measurement is widely used in dairy herds milked with automatic milking systems (AMS) and gives the opportunity to closely monitor individual cow udder health. Using automated SCC data, we observed cows displaying a remarkably regularly fluctuating SCC (rfSCC) pattern, which is described in this study. We aimed to (1) estimate the prevalence of rfSCC in cows milked by AMS, (2) characterize the rfSCC pattern, and (3) identify factors potentially associated with the rfSCC pattern. We analyzed 30-d episodes of composite SCC recordings of 1,000 cows from 55 dairy herds from 6 countries using an AMS with automated SCC measurement, and we identified the rfSCC pattern in 4.7% (95% CI: 3.5-6.2%) of these episodes. The rfSCC episodes had a median SCC of 701 × 1,000 cells/mL (2.5-97.5% quantile: 539-1,162), a median amplitude of 552 × 1,000 cells/mL (2.5-97.5% quantile: 409-886), and a median cycle length of 4.1 d (2.5-97.5% quantile: 3.7-4.9). Bacteriological culture data from quarter-milk samples collected every 2 wk in 1 Dutch AMS herd were analyzed, yielding no clear association between pathogen species and the rfSCC pattern found in that herd. Altogether, we described an intriguing phenomenon, present in almost 5% of the cows during a 1-mo study period. Further work is needed to quantify its importance in terms of udder health, but also to elucidate the mechanism behind this remarkable SCC pattern.

Monitoring udder health on routinely collected census data: Evaluating the short- to mid-term consequences of implementing selective dry cow treatment.

In 2013, the preventive use of antimicrobials in Dutch livestock was prohibited, including a ban on the blanket application of antimicrobial dry cow treatment (BDCT). Since then, selective dry cow treatment (SDCT) has become the standard approach. In this study, we aimed to determine the effect of the ban on BDCT and the extent of the subsequent adoption of SDCT on antimicrobial usage (AMU) and udder health on Dutch dairy farms. In the Dutch cattle health surveillance system, AMU for dry cow treatment (AMUDCT), AMU for intramammary treatment at any point in time (AMUIMM), and udder health indicators are routinely and continuously monitored. This provided the opportunity to study associations among SDCT, udder health, and AMU on census data of approximately 17,000 dairy herds, with about 1.67 million cows in total (>2 yr old) at one moment in time in the period from 2013 until 2017. Six udder health parameters were evaluated using multivariable population-averaged generalized estimating equation models. The year in which the ban on BDCT was introduced (2013) was compared with the period thereafter (2014-2017). Additionally, AMUIMM and AMUDCT were included as independent variables to evaluate whether the extent to which SDCT was implemented on the herd level was associated with udder health. Demographic parameters were included as potential confounders. Since the ban on BDCT, overall declines of 63% in AMUDCT and 15% in AMUIMM were observed. The raw data show an improvement in 5 out of 6 evaluated udder health parameters between 2013 and 2017. Nevertheless, the multivariable model results showed that the period since the ban on BDCT was associated with a small but significant increase in the percentage of cows with high somatic cell count (HSCC) and new HSCC (+0.41% and +0.06%, respectively). Additionally, the probability of belonging to the group of herds with more than 25% of primiparous cows having HSCC during the start of lactation increased slightly, associated with the period after which BDCT was banned (odds ratio = 1.08). The probability of belonging to the group of herds with more than 25% cows having a persistent HSCC during the dry period was not affected and bulk milk somatic cell count showed a slight but significant reduction. The only udder health parameter that notably worsened during the study period was the probability of belonging to the group of herds with more than 25% of multiparous cows with a new HSCC after the dry period, during the start of lactation (odds ratio = 1.23). In herds where the farmer decided not to apply any dry cow therapy (≈20% of all herds), all udder health parameters were poorer compared with herds in which dry cow therapy was applied to some extent. The ban on BDCT and implementation of SDCT in the Netherlands was associated with a considerable reduction in AMU without a major impairment in udder health at the national level. Although negative effects of changed dry cow management were observed in some herds, we conclude that SDCT can be introduced without substantial negative effects on udder health.

Adolescents' family obligation and activities in rural and urban Vietnam: Implications for social change.

This study examined how urbanisation may modify adolescents' values and activities concerning family obligation by surveying 572 adolescents (Mage  = 15.75, SD = .73) in rural and urban Vietnam. Compared with their rural peers, urban adolescents reported a stronger sense of family obligation but spent less time actually engaging in family assistance, findings that were partly explained by urban households' less financial hardship and higher parental education levels. As expected, stronger family obligation values were associated with greater family assistance activities across rural and urban Vietnam. However, stronger family obligation values were associated with more study hours only in urban Vietnam, indicating that urbanisation may broaden the meaning of family obligation to encompass the academic domain. Additionally, weaker family obligation values were associated with more employment hours only in rural Vietnam, suggesting that rural adolescents with little attachment to the traditional value of family obligation may pursue autonomy through employment outside the home. In traditionally familistic societies undergoing urbanisation, family obligation may take on different meaning depending on adolescents' ecological settings that construct cultural values and behavioural norms.

The ALERT model of care for the assessment and personalized management of patients with lymphoedema.

BACKGROUND: This study documents the development and evaluation of a comprehensive multidisciplinary model for the assessment and personalized care of patients with lymphoedema. METHODS: The Australian Lymphoedema Education Research and Treatment (ALERT) programme originated as an advanced clinic for patients considering surgery for lymphoedema. The programme commenced liposuction surgery in May 2012 and then introduced lymph node transfer in 2013 and lymphovenous anastomosis (LVA) in 2016. An outpatient conservative treatment clinic was established in 2016. ALERT commenced investigations with indocyanine green (ICG) lymphography in late 2015, leading to the creation of a diagnostic assessment clinic offering ICG in 2017. RESULTS: Since 2012, 1200 new patients have been referred to ALERT for assessment of lymphoedema for a total of 5043 episodes of care. The introduction of ICG lymphography in 2015 initially allowed better screening for LVA, but is now used not only to guide surgical options, but also as a diagnostic tool and to guide manual lymphatic drainage massage. The total number of new patients who attended the surgical assessment clinic to December 2018 was 477, with 162 patients (34·0 per cent) undergoing surgery. CONCLUSION: The ALERT programme has developed a multidisciplinary model of care for personalized lymphoedema treatment options based on clinical, imaging and ICG lymphography. Patients are selected for surgery based on several individual factors.

ANTECEDENTES: Este estudio presenta el desarrollo y valoración de un modelo multidisciplinario integral para la evaluación y atención personalizada de pacientes con linfedema. MÉTODOS: El programa australiano de educación en investigación y tratamiento del linfedema (Australian Lymphoedema Education Research and Treatment, ALERT) se originó como un centro clínico avanzado para pacientes que consideran la cirugía como tratamiento para el linfedema. El programa se inició en mayo del 2012 con la cirugía de liposucción, introduciendo la cirugía de transferencia ganglionar (lymph node transfer, LNT) en 2013 y la anastomosis linfovenosa (lymphovenous anastomosis, LVA) en 2016. En 2016 se estableció una clínica de tratamiento conservador ambulatorio. ALERT comenzó las investigaciones con la linfografía con verde de indocianina (indocyanine green, ICG) a fines del 2015, lo que se siguió de la creación de una clínica de evaluación diagnóstica que ofrece ICG en 2017. RESULTADOS: Desde el 2012, 1.200 pacientes nuevos han sido referidos a ALERT para la evaluación de un linfedema, con un total de 5.043 episodios atendidos. La introducción inicialmente de linfografía con ICG en 2015 permitió un mejor cribaje para LVA, pero actualmente se utiliza no solo como guía de las opciones quirúrgicas, sino también como herramienta diagnóstica y como guía del masaje de drenaje linfático manual (manual lymphatic drainage, MLD). El número total de pacientes nuevos atendidos en la clínica de evaluación quirúrgica hasta diciembre de 2018 fue de 477, con 122 pacientes (34%) tratados quirúrgicamente. El modelo tal como se ha descrito, ha atraído a pacientes de toda Australia y Nueva Zelanda. CONCLUSIÓN: El programa ALERT ha desarrollado un modelo multidisciplinario de atención para las opciones de tratamiento personalizado del linfedema basado en la evaluación clínica, por imagen (MRI y LSG) y linfografía con ICG. Los pacientes se seleccionan cuidadosamente para el tratamiento quirúrgico en función de varios factores relacionados con el paciente, el tumor, los linfáticos y las opciones terapéuticas, y se someten a una evaluación detallada después de cualquier procedimiento.

Antimicrobial use and farmers' attitude toward mastitis treatment on dairy farms with automatic or conventional milking systems.

Mastitis is one of the major causes for antimicrobial use on dairy cattle farms. On farms with an automatic milking system (AMS), diagnostics differ from those with a conventional milking system (CMS), with potentially a different attitude toward mastitis treatment. This may result in differences in antimicrobial usage (AMU) between these 2 types of farms. The aims of this study were (1) to compare AMU between AMS and CMS farms, (2) to identify variables associated with AMU in both types of herds, and (3) to describe the distribution of mastitis-causing pathogens and their antimicrobial resistance patterns. Data on AMU was collected for 42 AMS and 254 CMS farms in the Netherlands and was expressed as animal-defined daily dose (ADDD). The ADDD variables were total usage (ADDDTOTAL), intramammary usage during lactation (ADDDIMM), usage for dry cow therapy (ADDDDCT), and usage by injection (ADDDINJ). Eighteen AMS farms and 24 CMS farms participated in a survey on factors potentially related to AMU. These farmers collected 5 quarter milk samples from quarters with clinical mastitis or high somatic cell count, which were subjected to bacteriological culture and antimicrobial susceptibility testing. In addition, routinely collected udder health data of these farms were used in the analysis. Nonlinear principal component analysis (NLPCA) was used to explore associations between AMU, udder health, and questionnaire variables. The ADDDTOTAL and ADDDDCT were comparable between AMS and CMS farms, whereas ADDDIMM tended to be lower and ADDDINJ higher on AMS farms than on CMS farms. The NLPCA yielded 3 principal components (PC) that explained 48% of the variation in all these variables. The AMS farms were not distinguished from CMS farms in the principal component space. The 3 PC represented different aspects of udder health, ADDDTOTAL, and treatment strategy. Differences in treatment strategy were unrelated to total antimicrobial usage or overall udder health. The distribution of mastitis-causing pathogens and their antimicrobial resistance were comparable between AMS and CMS farms. In conclusion, our study shows that AMU on AMS farms was similar to that of CMS farms, but AMS farmers tend to apply more injectable and fewer intramammary treatments during lactation than CMS farmers. Across both farm types, farmers' attitudes toward udder health in general and toward mastitis treatment are associated with AMU.

Therapeutic Strategies to Reduce the Toxicity of Misfolded Protein Oligomers.

The aberrant aggregation of proteins is implicated in the onset and pathogenesis of a wide range of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Mounting evidence indicates that misfolded protein oligomers produced as intermediates in the aggregation process are potent neurotoxic agents in these diseases. Because of the transient and heterogeneous nature of these elusive aggregates, however, it has proven challenging to develop therapeutics that can effectively target them. Here, we review approaches aimed at reducing oligomer toxicity, including (1) modulating the oligomer populations (e.g., by altering the kinetics of aggregation by inhibiting, enhancing, or redirecting the process), (2) modulating the oligomer properties (e.g., through the size-hydrophobicity-toxicity relationship), (3) modulating the oligomer interactions (e.g., by protecting cell membranes by displacing oligomers), and (4) reducing oligomer toxicity by potentiating the protein homeostasis system. We analyze examples of these complementary approaches, which may lead to the development of compounds capable of preventing or treating neurodegenerative disorders associated with protein aggregation.