Screening of 152 Veterinary Drug Residues in Animal Source Foods by LC-MS/MS, Multilaboratory Validation Study: Final Action 2020.04.

BACKGROUND: The presence of veterinary drug residues in food-producing animals and animal products is regulated through the enforcement of maximum residue limits (MRLs). To answer the need of the food sector to monitor these substances in a wide range of food commodities, stakeholders at AOAC identified the need for a reliable confirmatory screening method. Such qualitative approach is required for compliance checking and to support product release in manufacturing. OBJECTIVE: Data were collected from 5 independent laboratories that applied the AOAC Official First Action Method AOAC 2020.04 to demonstrate adequate performance under reproducibility conditions. Probability of Detection (POD) was calculated in blank test samples and test samples spiked at the Screening Target Concentration (STC) level, with the objective to achieve PODs ≤ 10% and ≥ 90%, respectively. Additionally, the effectiveness of the screening method was assessed through participation to 92 proficiency test samples. METHODS: Four streams were optimized to screen for 152 veterinary drug residues by LC-MS/MS in a wide variety of food commodities including milk-based ingredients and related products (e.g., milk fractions, infant formula, infant cereals and baby foods), meat- and fish-based ingredients and related products (fresh, powdered, cooked, infant cereals and baby foods) and other ingredients such as eggs, animal fat and animal byproducts. The four streams covered 105 antibiotic residues, anti-inflammatory and antiparasitic agents (Stream A); 23 Beta-lactams (Stream B); 14 Aminoglycosides (Stream C) and 10 Tetracyclines (Stream D). RESULTS: The multi-laboratory validation led to PODs at the STC ≥ 94% and PODs in the blank ≤ 9%. Further application of the multi-laboratory validated method to 92 proficiency tests provided more than 99% satisfactory submitted results (n = 784). CONCLUSION: The inter-laboratory reproducibility determined for this method met the acceptance criteria defined in AOAC SMPR 2018.010. HIGHLIGHTS: AOAC has approved the method for Final Action Status.

Efficacy of Early Enhanced Occupational Therapy in an Intensive Care Unit (EFFORT-ICU): A Single-Site Feasibility Trial.

IMPORTANCE: This research trial contributes to the evidence for occupational therapy service delivery in intensive care settings. OBJECTIVE: To explore the feasibility of a trial to evaluate the impact of early enhanced occupational therapy on mechanically ventilated patients in intensive care. DESIGN: Single-site assessor-blinded randomized controlled feasibility trial. SETTING: Level 5 8-bed adult medical-surgical intensive care unit (ICU) at Logan Hospital, Brisbane, Australia. PARTICIPANTS: Participants were 30 mechanically ventilated patients randomly allocated to two groups. OUTCOMES AND MEASURES: We compared standard care with enhanced occupational therapy with outcomes measured at discharge from the ICU, hospital discharge, and 90 days post randomization. The primary outcome measure was the FIM®. Secondary outcomes included the Modified Barthel Index (MBI); Montreal Cognitive Assessment; grip strength, measured using a dynamometer; Hospital Anxiety and Depression Scale; and the 36-Item Short-Form Health Survey (Version 2). The intervention group received daily occupational therapy, including cognitive stimulation, upper limb retraining, and activities of daily living. Data were analyzed using independent groups t tests and effect sizes. RESULTS: Measures and procedures were feasible. A significant difference was found between groups on FIM Motor score at 90 days with a large effect size (p = .05, d = 0.76), and MBI scores for the intervention group approached significance (p = .051) with a large effect size (d = 0.75) at 90 days. Further moderate to large effect sizes were obtained for the intervention group for cognitive status, functional ability, and quality of life. CONCLUSIONS AND RELEVANCE: This trial demonstrated that occupational therapy is feasible and beneficial in the ICU. Criteria to progress to a full-scale randomized controlled trial were met. This study contributes to embedding ongoing consistency of practice and scope of service delivery for occupational therapy in this field. What This Article Adds: Occupational therapists should be considered core team members in the critical care-ICU, with funding to support ongoing service provision and optimization of patient outcomes based on effective and feasible service delivery.

Occupational therapy service provision in adult intensive care units in Australia: A survey of workload practices, interventions and barriers.

INTRODUCTION: Occupational therapy practice within intensive care units (ICUs) is limited with respect to published research evidence and guidelines regarding scope of practice. An understanding of the current level of service provision, feasibility of services in ICUs and training and development needs of occupational therapists is required to enable consistent best practice and promote the occupational therapy profile. This study aimed to explore occupational therapy practice within ICUs in Australia including the barriers and enablers to practice perceived by occupational therapists. METHODS: In this cross-sectional study, a national customised online survey was completed by registered occupational therapists who provide services in intensive care settings in Australia. Recruitment was from July to September 2019 through Occupational Therapy Australia and other professional networks and interest groups. RESULTS: The survey was completed by 43 respondents. The majority were experienced therapists from Queensland with greater than 10-years post-qualification and working in a tertiary hospital setting. The most common length of time spent working in the ICU was 0-2 h per week. Formal and informal self-care measures, cognitive screens and physical outcome measures were commonly used. Bed-based grooming retraining, pressure care management, functional upper limb retraining and passive ranging were the most frequent interventions provided on a daily basis. Perceived barriers to occupational therapy service provision in ICU included lack of funding for staffing, competing workload demands, lack of occupational therapy role delineation and scope of practice and lack of published evidence and training. CONCLUSION: Occupational therapy services in intensive care settings in Australia are limited. Published practice guidelines, further research, applications for service funding and ongoing education of the ICU multidisciplinary team regarding the scope of occupational therapy practice are recommended to promote the development of occupational therapy services in ICU.

Short-Term Treatment with Alirocumab, Flow-Dependent Dilatation of the Brachial Artery and Use of Magnetic Resonance Diffusion Tensor Imaging to Evaluate Vascular Structure: An Exploratory Pilot Study.

BACKGROUND: Short-term effects of alirocumab on vascular function have hardly been investigated. Moreover, there is a scarce of reliable non-invasive methods to evaluate atherosclerotic changes of the vasculature. The ALIROCKS trial was performed to address these issues using standard ultrasound-based procedures and a completely novel magnetic resonance-based imaging technique. METHODS: A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were 2 visits to the study site, the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. The key outcome measures included the change of carotid vessel wall fractional anisotropy, a novel magnetic resonance-based measure of vascular integrity, and the changes of carotid intima-media thickness and flow-dependent dilatation of the brachial artery measured with ultrasound. RESULTS: A total of 19 patients completed the trial, 2 patients stopped treatment, 3 patients did not undergo the second visit due to the COVID pandemic. All of them had atherosclerotic vascular disease. Their mean (standard deviation) LDL-cholesterol concentration was 154 (85) mg/dL at baseline and was reduced by 76 (44) mg/dL in response to alirocumab treatment (p < 0.001, n = 19). P-selectin and vascular endothelial growth factors remained unchanged. Flow-dependent dilatation of the brachial artery (+41%, p = 0.241, n = 18), carotid intima-media thickness (p = 0.914, n = 18), and fractional anisotropy of the carotid artery (p = 0.358, n = 13) also did not significantly change. CONCLUSION: Despite a nominal amelioration for flow-dependent dilatation, significant effects of short-term treatment with alirocumab on vascular function were not detectable. More work would be needed to evaluate, whether fractional anisotropy may be useful in clinical atherosclerosis research.

Effects of Alirocumab on Triglyceride Metabolism: A Fat-Tolerance Test and Nuclear Magnetic Resonance Spectroscopy Study.

BACKGROUND: PCSK9 antibodies strongly reduce LDL cholesterol. The effects of PCSK9 antibodies on triglyceride metabolism are less pronounced. The present study aimed to investigate in detail the effects of alirocumab on triglycerides, triglyceride-rich lipoproteins, and lipase regulators. METHODS: A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were two visits at the study site: the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. Fat-tolerance tests, nuclear magnetic resonance spectroscopy, and enzyme-linked immunosorbent assays were performed to analyze lipid metabolism. RESULTS: A total of 21 participants underwent the first and second investigation. Among these, two participants only received alirocumab twice and 19 patients completed the trial per protocol. All of them had atherosclerotic vascular disease. There was no significant effect of alirocumab treatment on fasting triglycerides, post-prandial triglycerides, or lipoprotein-lipase regulating proteins. Total, large, and small LDL particle concentrations decreased, while the HDL particle concentration increased (all p < 0.001). Mean total circulating PCSK9 markedly increased in response to alirocumab treatment (p < 0.001). Whereas PCSK9 increased more than three-fold in all 19 compliant patients, it remained unchanged in those two patients with two injections only. CONCLUSION: Significant effects of alirocumab on triglyceride metabolism were not detectable in the ALIROCKS trial. The total circulating PCSK9 concentration might be a useful biomarker to differentiate non-adherence from non-response to PCSK9 antibodies.

Fatores que influenciam a adesão à lista de verificação de segurança cirúrgica / Factors that influence the adherence to the surgical safety checklist / Factores que influyen en la adhesión a la lista de control de seguridad quirúrgica

Objetivo: Identificar a percepção dos profissionais em relação à utilização da Lista de Verificação de Segurança Cirúrgica e mapear os fatores que podem potencializar ou fragilizar o preenchimento e a adesão. Método: Estudo transversal, com abordagem mista. A coleta foi realizada pela aplicação de entrevista com os profissionais de saúde que atuam em um centro cirúrgico de um hospital público de município do Sul do país, no período de fevereiro a junho de 2019. Resultados: Elencaram-se as seguintes categorias: potencialidades e fragilidades na aplicação da lista; 96,6% concordaram totalmente que se sentiam mais seguros em participar de procedimentos em que o checklist é aplicado e 90,2% e concordaram que proporciona boa comunicação. Porém 39,9% discordam de que toda a equipe participe da aplicação e 69,9% concordam que nem sempre a lista é aplicada em função da resistência ou pouca praticidade. Conclusão: Os profissionais reconhecem que a aplicabilidade da lista proporciona segurança para o processo cirúrgico, porém uma das fragilidades foi a baixa adesão da equipe em realizar o passo a passo proposto.

Objective: To identify the perception of professionals regarding the use of the Surgical Safety Checklist and map the factors that can enhance or weaken its completion and adherence. Method: Cross-sectional study with a mixed approach. Data collection was carried out by applying an interview with health professionals who work in a surgical center of a public hospital in the south of the country, from February to June 2019. Results: The following categories were listed: strengths and weaknesses in the application of the list; 96.6% strongly agreed that they felt safer to participate in procedures in which the checklist is applied and 90.2% agreed that it provides good communication. However, 39.9% disagreed that the entire team participates in its applica-tion and 69.9% agreed that the list is not always applied due to resistance or impracticality. Conclusion: The professionals recognize that the applicability of the list provides security for the surgical process, but one of the weaknesses was the low adherence of the team to carry out the proposed step by step.

Objetivo: Identificar la percepción de los profesionales sobre el uso de la Lista de Verificación de Seguridad Quirúrgica (LVSQ) y mapear los factores que pueden mejorar o debilitar el llenado y la adherencia. Método: Estudio transversal con enfoque mixto. La recolección se realizó mediante la aplicación de una entrevista a profesionales de la salud que laboran en un centro quirúrgico de un hospital público de una ciudad del sur del país, de febrero a junio de 2019. Resultados: Se enumeraron las siguientes categorías: potenciales y debilidades en la aplicación de la LVSQ; El 96,6% está total-mente de acuerdo en que se siente más seguro al participar en los procedimientos donde se aplica la LVSQ y el 90,2% está de acuerdo en que propor-ciona una buena comunicación. Sin embargo, el 39,9% no está de acuerdo con que todo el equipo participe en la aplicación y el 69,9% está de acuerdo en que la LVSQ no siempre se aplica, por su resistencia o poca practicidad. Conclusión: Los profesionales reconocen que la aplicabilidad de la LVSQ brinda seguridad al proceso quirúrgico, pero una de las debilidades fue la baja adherencia del equipo en la realización del procedimiento paso a paso propuesto.

Effects of a Protein-Rich, Low-Glycaemic Meal Replacement on Changes in Dietary Intake and Body Weight Following a Weight-Management Intervention-The ACOORH Trial.

Although meal replacement can lead to weight reduction, there is uncertainty whether this dietary approach implemented into a lifestyle programme can improve long-term dietary intake. In this subanalysis of the Almased Concept against Overweight and Obesity and Related Health Risk (ACOORH) study (n = 463), participants with metabolic risk factors were randomly assigned to either a meal replacement-based lifestyle intervention group (INT) or a lifestyle intervention control group (CON). This subanalysis relies only on data of participants (n = 119) who returned correctly completed dietary records at baseline, and after 12 and 52 weeks. Both groups were not matched for nutrient composition at baseline. These data were further stratified by sex and also associated with weight change. INT showed a higher increase in protein intake related to the daily energy intake after 12 weeks (+6.37% [4.69; 8.04] vs. +2.48% [0.73; 4.23], p < 0.001) of intervention compared to CON. Fat and carbohydrate intake related to the daily energy intake were more strongly reduced in the INT compared to CON (both p < 0.01). After sex stratification, particularly INT-women increased their total protein intake after 12 (INT: +12.7 g vs. CON: -5.1 g, p = 0.021) and 52 weeks (INT: +5.7 g vs. CON: -16.4 g, p = 0.002) compared to CON. Protein intake was negatively associated with weight change (r = -0.421; p < 0.001) after 12 weeks. The results indicate that a protein-rich dietary strategy with a meal replacement can improve long-term nutritional intake, and was associated with weight loss.

A comparison of standard occupational therapy versus early enhanced occupation-based therapy in a medical/surgical intensive care unit: study protocol for a single site feasibility trial (EFFORT-ICU).

BACKGROUND: Admissions to intensive care units (ICUs) are increasing due to an ageing population, and rising incidence of cardiac and respiratory disease. With advances in medical care, more patients are surviving an initial stay in critical care; however, they can experience ongoing health and cognitive limitations that may influence return to baseline function up to a year post-admission. Recent research has focused on the introduction of early rehabilitation within the ICU to reduce long-term physical and cognitive complications. The aim of this study is to explore the feasibility and impact of providing early enhanced occupation-based therapy, including cognitive stimulation and activities of daily living, to patients in intensive care. METHODS: This study involves a single site randomised-controlled feasibility trial comparing standard occupational therapy care to an early enhanced occupation-based therapy. Thirty mechanically ventilated ICU patients will be recruited and randomly allocated to the intervention or control group. The primary outcome measure is the Functional Independence Measure (FIM), and secondary measures include the Modified Barthel Index (MBI), Montreal Cognitive Assessment (MoCA), grip strength, Hospital Anxiety and Depression Scale (HADS) and Short-Form 36 Health survey (SF-36). Measures will be collected by a blind assessor at discharge from intensive care, hospital discharge and a 90-day follow-up. Daily outcome measures including the Glasgow Coma Scale (GCS), Richmond Agitation and Sedation Scale (RASS) and Confusion Assessment Measure for intensive care units (CAM-ICU) will be taken prior to treatment. Participants in the intervention group will receive daily a maximum of up to 60-min sessions with an occupational therapist involving cognitive and functional activities such as self-care and grooming. At the follow-up, intervention group participants will be interviewed to gain user perspectives of the intervention. Feasibility data including recruitment and retention rates will be summarised descriptively. Parametric tests will compare outcomes between groups. Interview data will be thematically analysed. DISCUSSION: This trial will provide information about the feasibility of investigating how occupational therapy interventions in ICU influence longer term outcomes. It seeks to inform the design of a phase III multicentre trial of occupational therapy in critical care general medical intensive care units. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry (ANZCTR): ACTRN12618000374268 ; prospectively registered on 13 March 2018/ https://www.anzctr.org.au Trial funding: Metro South Health Research Support Scheme Postgraduate Scholarship.

Screening of 154 Veterinary Drug Residues in Foods of Animal Origin Using LC-MS/MS: First Action 2020.04.

BACKGROUND: Veterinary drug residues in food are substances (>200 compounds) exhibiting potential health risks for consumers, thus being regulated in national legislations and the Codex Alimentarius. Most of the compounds are regulated based upon a maximum residue limit (MRL) while a few of them are banned in food for humans. The food sector needs a reliable and consensus analytical platform able to monitor these substances in a wide range of food commodities. OBJECTIVE: Several confirmatory methods based on liquid chromatography-mass spectrometry are available in the literature for either screening or quantification of veterinary drug residues in food, but usually applicable to limited scope of matrices. The current work describes the single-laboratory validation (SLV) of a method for screening 154 veterinary drug residues in several food categories. METHODS: This work describes a streamlined platform making use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for screening 105 antibiotics, 41 antiparasitics, 5anti-inflammatory agents, and 3 tranquilizers in foods of animal origin. For the best performance across the commodities (dairy-, meat-, fish-, and egg-based materials), four method streams were established. As a screening tool, probabilities of detection (PODs) were assessed at the screening target concentration (STC < MRL) and the blank. RESULTS: The SLV led to PODs at the STC >94% and PODs in the blank < 4%. CONCLUSION: Performance is in agreement with the acceptance criteria defined in SMPR 2018.010. HIGHLIGHTS: The Expert Review Panel approved the present method as AOAC Official First Action 2020.04.

Humeral head resurfacing is associated with less pain and clinically equivalent functional outcomes compared with stemmed hemiarthroplasty at mid-term follow-up.

PURPOSE: Humeral head resurfacing (HHR) is a less invasive, anatomic alternative to the conventional stemmed hemiarthroplasty in patients in whom isolated humeral head replacement is preferred. It was hypothesized that, in a mid-term cross-sectional subjective outcome analysis, HHR would have equivalent patient-reported and functional outcomes to stemmed hemiarthroplasty (HA). METHODS: A total of 213 HHR and 153 HA procedures were performed at a single academic institution from 2000 to 2014. Of these, 106 HHR and 47 HA patients corresponding with 120 HHR and 55 HA shoulders responded to a survey that collected patient demographics, surgical outcomes, patient satisfaction, and self-reported range of motion scores using both bespoke and validated metrics. RESULTS: Follow-up was longer in the HA group (9.4 ± 3.4 vs. 5.2 ± 1.8 years, p < 0.0001). Self-reported range of motion was equivalent between groups. Surgery was perceived as helpful following 76.7% of HHRs and 78.2% of HAs (p > 0.99). The ASES pain subscore was significantly worse in the HA group (25.2 ± 29.5 vs. 38.5 ± 12.7 after HHR, p < 0.0001), which translated into worse ASES total scores (45.1 ± 14.8 HA vs. 52.2 ± 23.7 HHR, p < 0.05). These findings were equivocal in responses received 2-8 years vs. ≥ 8 years after surgery. CONCLUSIONS: Indications should be equivocal; humeral head resurfacing is a viable alternative to hemiarthroplasty, with equivalent patient satisfaction and reduced pain in the mid-term post-operative period. LEVEL OF EVIDENCE: III.

Neutrophil-lymphocyte ratio in the early diagnosis of sepsis in an intensive care unit: a case-control study. / Razão neutrófilo-linfócito no diagnóstico precoce de sepse em unidade de terapia intensiva: um estudo de caso-controle.

OBJECTIVE: To evaluate the neutrophil-lymphocyte ratio as a predictor of sepsis and mortality in patients admitted to an intensive care unit. METHODS: Case-control study of adult patients admitted to an intensive care unit. Patients who had sepsis as the reason for admission and who had a previous complete blood count examination were included as case patients. The following statistical analyses were performed: ROC curves, binary logistic regression, and Mann-Whitney and Pearson's chi-square tests. p < 0.05 was considered significant. RESULTS: The ROC curve values were 0.62 for neutrophil-lymphocyte ratio, 0.98 for band neutrophils and 0.51 for total leukocytes. The presence of a neutrophil-lymphocyte ratio greater than 5.0, leukocyte count above 12,000mm3/mL and band neutrophil percentage above 10% were risk factors for sepsis; however, only the SAPS 3 and SOFA score were related to patient mortality. CONCLUSION: The neutrophil-lymphocyte ratio and band neutrophils in combination with other parameters may be markers for the early detection of sepsis in intensive care units.

OBJETIVO: Avaliar a razão neutrófilo-linfócito na predição de sepse e mortalidade em pacientes admitidos em uma unidade de terapia intensiva. MÉTODOS: Estudo de caso-controle de pacientes adultos admitidos em terapia intensiva. Foram incluídos como casos pacientes que tiveram sepse como razão de admissão e possuíam exame laboratorial de hemograma prévio. As análises estatísticas realizadas foram curva ROC, regressão logística binária, Mann Whitney e qui-quadrado de Pearson. Foi considerado significativo valor de p < 0,05. RESULTADOS: Os valores de curva ROC foram 0,62 para razão neutrófilo-linfócito, 0,98 para neutrófilos bastonados e 0,51 para leucócitos totais. A presença de razão neutrófilo-linfócito superior a 5,0, o número de leucócitos acima de 12.000mm3/mL e número de neutrófilos bastonados acima 10% foram fatores de risco para sepse, entretanto somente os escores SAPS 3 e SOFA estavam relacionados a mortalidade dos pacientes. CONCLUSÃO: A razão neutrófilo-linfócito e os neutrófilos bastonados em combinação com outros parâmetros podem ser marcadores na detecção precoce de sepse em terapia intensiva.

Razão neutrófilo-linfócito no diagnóstico precoce de sepse em unidade de terapia intensiva: um estudo de caso-controle / Neutrophil-lymphocyte ratio in the early diagnosis of sepsis in an intensive care unit: a case-control study

RESUMO Objetivo: Avaliar a razão neutrófilo-linfócito na predição de sepse e mortalidade em pacientes admitidos em uma unidade de terapia intensiva. Métodos: Estudo de caso-controle de pacientes adultos admitidos em terapia intensiva. Foram incluídos como casos pacientes que tiveram sepse como razão de admissão e possuíam exame laboratorial de hemograma prévio. As análises estatísticas realizadas foram curva ROC, regressão logística binária, Mann Whitney e qui-quadrado de Pearson. Foi considerado significativo valor de p < 0,05. Resultados: Os valores de curva ROC foram 0,62 para razão neutrófilo-linfócito, 0,98 para neutrófilos bastonados e 0,51 para leucócitos totais. A presença de razão neutrófilo-linfócito superior a 5,0, o número de leucócitos acima de 12.000mm3/mL e número de neutrófilos bastonados acima 10% foram fatores de risco para sepse, entretanto somente os escores SAPS 3 e SOFA estavam relacionados a mortalidade dos pacientes. Conclusão: A razão neutrófilo-linfócito e os neutrófilos bastonados em combinação com outros parâmetros podem ser marcadores na detecção precoce de sepse em terapia intensiva.

ABSTRACT Objective: To evaluate the neutrophil-lymphocyte ratio as a predictor of sepsis and mortality in patients admitted to an intensive care unit. Methods: Case-control study of adult patients admitted to an intensive care unit. Patients who had sepsis as the reason for admission and who had a previous complete blood count examination were included as case patients. The following statistical analyses were performed: ROC curves, binary logistic regression, and Mann-Whitney and Pearson's chi-square tests. p < 0.05 was considered significant. Results: The ROC curve values were 0.62 for neutrophil-lymphocyte ratio, 0.98 for band neutrophils and 0.51 for total leukocytes. The presence of a neutrophil-lymphocyte ratio greater than 5.0, leukocyte count above 12,000mm3/mL and band neutrophil percentage above 10% were risk factors for sepsis; however, only the SAPS 3 and SOFA score were related to patient mortality. Conclusion: The neutrophil-lymphocyte ratio and band neutrophils in combination with other parameters may be markers for the early detection of sepsis in intensive care units.

Preoperative Comorbidities and Postoperative Complications Do Not Influence Patient-Reported Satisfaction Following Humeral Head Resurfacing: Mid- to Long-term Follow-up of 106 Patients.

BACKGROUND: Humeral head resurfacing (HHR) has emerged as an alternative treatment for glenohumeral osteoarthritis. We investigated the outcomes of HHR using validated patient-reported outcome (PRO) measures. METHODS: A retrospective review was performed on 213 patients who underwent HHR. A PRO follow-up was performed by administering a questionnaire including the American Shoulder and Elbow Society (ASES) score, Brophy activity survey, short form of the Disabilities of the Arm, Shoulder and Hand (quickDASH) survey, and general shoulder function. PRO scores were stratified by comorbidities and complications. RESULTS: Survey responses were received from 106 patients (51%), with a mean follow-up of 5.6 ± 1.8 years (range: 9 months to 6.1 years). Preoperative comorbidities were associated with significantly higher quickDASH scores. Postoperative complications were associated with significantly higher rates of current pain, higher visual analog scale scores, night pain, lower subjective shoulder values, and lower ASES pain and total scores. No differences in patient satisfaction were identified between the cohorts with and without preoperative comorbidities and between the cohorts with and without postoperative complications. CONCLUSION: In our cross-sectional analysis of mid- to long-term outcomes following HHR, preoperative comorbidities, or postoperative complications had no impact on patient-perceived postoperative satisfaction or most PROs. HHR is clinically viable in a wide variety of patients. Future work is necessary to compare the efficacy of HHR compared with more traditional total shoulder arthroplasty and stemmed hemiarthroplasty regarding long-term outcomes and appropriate indications.

Single-cell RNA sequencing reveals developmental heterogeneity of blastomeres during major genome activation in bovine embryos.

Embryonic development is initially controlled by maternal RNAs and proteins stored in the oocyte, until gene products gradually generated by the embryo itself take over. Major embryonic genome activation (EGA) in bovine embryos occurs at the eight- to 16-cell stage. Morphological observations, such as size of blastomeres and distribution of microvilli, suggested heterogeneity among individual cells already at this developmental stage. To address cell heterogeneity on the transcriptome level, we performed single-cell RNA sequencing of 161 blastomeres from 14 in vitro produced bovine embryos at Day 2 (n = 6) and Day 3 (n = 8) post fertilization. Complementary DNA libraries were prepared using the Single-Cell RNA-Barcoding and Sequencing protocol and sequenced. Non-supervised clustering of single-cell transcriptome profiles identified six clusters with specific sets of genes. Most embryos were comprised of cells from at least two different clusters. Sorting cells according to their transcriptome profiles resulted in a non-branched pseudo-time line, arguing against major lineage inclination events at this developmental stage. In summary, our study revealed heterogeneity of transcriptome profiles among single cells in bovine Day 2 and Day 3 embryos, suggesting asynchronous blastomere development during the phase of major EGA.

Screening of 23 ß-lactams in foodstuffs by LC-MS/MS using an alkaline QuEChERS-like extraction.

A fast and robust high performance LC-MS/MS screening method was developed for the analysis of ß-lactam antibiotics in foods of animal origin: eggs, raw milk, processed dairy ingredients, infant formula, and meat- and fish-based products including baby foods. QuEChERS extraction with some adaptations enabled 23 drugs to be simultaneously monitored. Screening target concentrations were set at levels adequate to ensure compliance with current European, Chinese, US and Canadian regulations. The method was fully validated according to the European Community Reference Laboratories Residues Guidelines using 93 food samples of different composition. False-negative and false-positive rates were below 5% for all analytes. The method is adequate for use in high-routine laboratories. A 1-year study was additionally conducted to assess the stability of the 23 analytes in the working standard solution.

Stability study of veterinary drugs in standard solutions for LC-MS/MS screening in food.

A study on stability of veterinary drugs in standard solutions stored at -80°C and at -20°C was conducted over 1 year. Data were acquired on 152 individual stock standard solutions and also on 15 family mixes and 2 working standard solutions. All solutions were prepared, stored and compared 1 year later against freshly prepared ones by LC-MS/MS. A statistical analysis was performed to set the acceptability criteria, taking into account the variability of standard preparations. In individual stock standard solutions stored at -80°C (12 months) and -20°C (9 months), stability was demonstrated for 141 and 140 out of 152 compounds, i.e. for 92% and 93% of compounds, respectively. Drugs were even more stable when solubilised in either diluted family mixes or working standard solutions, with more than 99% and 94% of compounds found unaltered when stored at -80°C and at -20°C, respectively. In mixes, beta-lactams from the cephalosporin (cefadroxil and cephalexin) and penicillin (amoxicillin and ampicillin) families were found to be the least stable compounds when stored at -20°C (6 months), necessitating storage at -80°C to achieve a 1-year shelf life. The study also evidenced solubility issues for two sulfonamides (sulfadiazine and sulfamerazine) in methanol-based solutions. An independent stability study conducted by a second laboratory confirmed the 1-year stability of 3 family mixes-quinolones, sulfonamides and tetracyclines.

Stage-specific proteome signatures in early bovine embryo development.

Development of early embryonic stages before activation of the embryonic genome depends on sufficiently stored products of the maternal genome, adequate recruitment and degradation of mRNAs, as well as activation, deactivation, and relocation of proteins. By application of an isobaric tagging for relative and absolute quantification (iTRAQ)-based approach, the proteomes of bovine embryos at the zygote and 2-cell and 4-cell stage with MII oocytes as a reference were quantitatively analyzed. Of 1072 quantified proteins, 87 differed significantly in abundance between the four stages. The proteomes of 2-cell and 4-cell embryos differed most from the reference MII oocyte, and a considerable fraction of proteins continuously increased in abundance during the stages analyzed, despite a strongly attenuated rate of translation reported for this period. Bioinformatic analysis revealed particularly interesting proteins involved in the p53 pathway, lipid metabolism, and mitosis. Verification of iTRAQ results by targeted SRM (selected reaction monitoring) analysis revealed excellent agreement for all five proteins analyzed. By principal component analysis, SRM quantifications comprising a panel of only five proteins were shown to discriminate between all four developmental stages analyzed here. For future experiments, an expanded SRM protein panel will provide the potential to detect developmental disturbances with high sensitivity and enable first insights into the underlying molecular pathways.

Sexual values as the key to maintaining satisfying sex after prostate cancer treatment: the physical pleasure-relational intimacy model of sexual motivation.

Sexual dysfunction is the most significant long lasting effect of prostate cancer (PrCa) treatment. Despite the many medical treatments for erectile dysfunction, many couples report that they are dissatisfied with their sexual relationship and eventually cease sexual relations altogether. We sought to understand what distinguishes successful couples from those who are not successful in adjusting to changes in sexual function subsequent to PrCa treatment. Ten couples who maintained satisfying sexual intimacy after PrCa treatment and seven couples that did not were interviewed conjointly and individually. Interviews were transcribed and analyzed using grounded theory methodology. The theory that resulted suggests that individuals are motivated to engage in sex primarily because of physical pleasure and relational intimacy. The couples who valued sex primarily for relational intimacy were more likely to successfully adjust to changes in sexual function than those who primarily valued sex for physical pleasure. The attributes of acceptance, flexibility, and persistence helped sustain couples through the process of adjustment. Based on these findings, a new theory, the Physical Pleasure-Relational Intimacy Model of Sexual Motivation (PRISM) is presented. The results elucidate the main motives for engaging in sexual activity-physical pleasure and/or relational intimacy-as a determining factor in the successful maintenance of satisfying sexual intimacy after PrCa treatment. The PRISM model predicts that couples who place a greater value on sex for relational intimacy will better adjust to the sexual challenges after PrCa treatment than couples who place a lower value on sex for relational intimacy. Implications of the model for counselling are discussed. This model remains to be tested in future research.

A brief couples' workshop for improving sexual experiences after prostate cancer treatment: a feasibility study.

PURPOSE: The most difficult survivorship issue reported by prostate cancer patients is the dramatic changes in their sexual relationships. The purpose of this study was to investigate the feasibility of a workshop designed to improve patients' and partners' sexual relationships. METHOD: Participants attended one 3.5-h workshop. A total of three separate workshops were held over a 12-month period. Patients and partners complete the Sexual Functioning Questionnaire (SFQ) prior, 2 months following, and if couples registered early enough, 2 months before the workshop. Change scores were calculated. RESULTS: Over the three workshops, 77 participants attended. All targets were met for feasibility and acceptability. Patients and partners both demonstrated significant gains on the medical impact subscale of the SFQ, and partners also demonstrated significant gains in sexual interest, problems, and total sexual function. CONCLUSIONS: The results suggest that attending one 3.5-h workshop that is offered every 4 months is feasible and acceptable to patients and their partners. Furthermore, the SFQ proves to be a sensitive assessment instrument of sexual function for patients and their partners.

Visualizing ribosome biogenesis: parallel assembly pathways for the 30S subunit.

Ribosomes are self-assembling macromolecular machines that translate DNA into proteins, and an understanding of ribosome biogenesis is central to cellular physiology. Previous studies on the Escherichia coli 30S subunit suggest that ribosome assembly occurs via multiple parallel pathways rather than through a single rate-limiting step, but little mechanistic information is known about this process. Discovery single-particle profiling (DSP), an application of time-resolved electron microscopy, was used to obtain more than 1 million snapshots of assembling 30S subunits, identify and visualize the structures of 14 assembly intermediates, and monitor the population flux of these intermediates over time. DSP results were integrated with mass spectrometry data to construct the first ribosome-assembly mechanism that incorporates binding dependencies, rate constants, and structural characterization of populated intermediates.