Quantum Spectral Analysis by Continuous Measurement of Landau-Zener Transitions.

We demonstrate the simultaneous estimation of signal frequency and amplitude by a single quantum sensor in a single experimental shot. Sweeping the qubit splitting linearly across a span of frequencies induces a nonadiabatic Landau-Zener transition as the qubit crosses resonance. The signal frequency determines the time of the transition, and the amplitude its extent. Continuous weak measurement of this unitary evolution informs a parameter estimator retrieving precision measurements of frequency and amplitude. Implemented on radio-frequency-dressed ultracold atoms read out by a Faraday spin-light interface, we sense a magnetic signal with estimated sensitivities to amplitude of 11 pT/sqrt[Hz], frequency 0.026 Hz/Hz^{3/2}, and phase 0.084 rad/sqrt[Hz], in a single 300 ms sweep from 7 to 13 kHz. The protocol realizes a swept-sine quantum spectrum analyzer, potentially sensing hundreds or thousands of channels with a single quantum sensor.

The acceptability, practicality, implementation and efficacy of a physical and social activity intervention 'BreatheHappy' for people with long-term respiratory conditions: A feasibility study.

OBJECTIVES: This study aimed to determine the feasibility of a group-based pilot programme of low-to-moderate physical activity training, education and social activities, by investigating acceptability, practicality, implementation and efficacy testing. We offer suggestions on programme adaptions for future study. METHODS: People with a range of chronic respiratory diseases were invited to participate in a pilot 12 week group activity programme. Activities included outdoor walking, tai-chi, education and a range of social activities. Acceptability was determined by participant experiences determined during interviews. Practicality was determined by programme and outcome measure completion, cost and adverse events. Implementation was determined according to whether the programme ran as planned. Efficacy was determined by statistical analyses of outcomes including hand grip strength, timed up and go test, COPD Helplessness Index, COPD Assessment Test, and measures of physical activity via accelerometry. RESULTS: Thematic analysis indicated that the "BreatheHappy" programme was acceptable. Seven of nine participants completed eight out of 10 sessions and the majority completed all outcome measures. "BreatheHappy" was therefore considered practical. The programme was not implemented as planned, with only 10 sessions running rather than the 12 intended. There was a significant increase in daily step counts (MD: 1284 95% CI: 240-2329 p: 0.024 effect size: 0.988), stepping time (MD: 16 min 95% CI: 5-27 min p: 0.011 effect size: 1.36) and daily minutes completing light physical activity (MD: 23 95% CI: 6-38 p: 0.006 effect size: 1.6). However, time spent sitting for ≥30 min but ≤60 min significantly increased (MD: 26 95% CI: 0.2-52 min p: 0.049 effect size: 0.931), showing signs of efficacy and changing physical activity behaviour patterns. DISCUSSION: A 10-week programme of low-moderate physical activity training, education and social activities shows signs of feasibility for future research. Suggested adaptions for future study include using physical activity measures such as daily step count or light physical activity for a primary outcome, and mental health and social health related outcome measures relatable to participant's beneficial experiences of the programme. Recruitment in future studies will try and reach both those less socially active and possibly those who have completed pulmonary rehabilitation (PR). Venues should be close to efficient transport links whilst different frequencies and durations of programme delivery should be trialled. Adequate funding should be provided for both staff running the programme and blinded research staff for outcome measurement.

Strategic Operational Redesign Improves Prior Authorization Access: A Validation Study.

Purpose: Obtaining prior authorization (PA) before treatment is becoming increasingly burdensome in oncology, especially in radiation oncology. Here, we describe the impact of a strategic novel operational PA redesign to shorten authorization time and to improve patient access to cancer care at a large United States academic proton therapy center. We ask whether such a redesign may be replicable and adoptable across oncology centers. Materials and Methods: Our PA redesign strategy was based on a 3-tiered approach. Specifically, we (1) held payors accountable to legally backed timelines, (2) leveraged expertise on insurance policies and practices, and (3) updated the submission, appeal writing, and planning procedures for PA. Metrics were compared at the following 3 time points: 6 months before, at phase-in, and at 6 months after intervention. Results: In analyzing the impact of improving PA access to care, the percentage of approvals for commercial proton beam therapy improved by an absolute 30.6% postintervention (P < .001). The proportion of commercially insured patients treated with proton beam therapy also increased by 6.2%, and the number of new starts rose by 11.7 patients/mo. Overall patient census increased by 13 patients/d. Median authorization time was 1 week, and 90% of surveyed providers reported reduced PA burden and improved patient care. Conclusion: This is the first validated, comprehensive operational strategy to improve access to cancer therapy while reducing the burden of PA. This novel approach may be helpful for addressing barriers to PA in medical and surgical oncology because the redesign is predicated on laws that regulate PA across disciplines.

Adipocyte size, adipose tissue fibrosis, macrophage infiltration and disease risk are different in younger and older individuals with childhood versus adulthood onset obesity.

BACKGROUND: The timing of obesity onset and age have been shown to affect the risk of obesity-related comorbidities, although the impact of each of these factors on markers of adipose tissue function remains unclear. OBJECTIVE: The aim of this study was to determine whether differences in regional adipose tissue characteristics vary with age and age of obesity onset, and whether these differences are associated with the markers of cardiometabolic health. METHODS: Adipose tissue samples were obtained from 80 female bariatric surgery candidates who were classified by age of obesity onset and age into 4 groups: (1) younger adults (<40 y) with childhood-onset obesity (<18 y) (Child-Young); (2) younger adults with adulthood-onset obesity (>18 y) (Adult-Young); (3) older adults (>55 y) with childhood-onset obesity (Child-Old); and (4) older adults with adulthood-onset obesity (Adult-Old). Adipocyte diameter, adipose tissue fibrosis, and macrophage infiltration were determined in subcutaneous (SAT) and visceral adipose tissue (VAT). Clinical parameters were obtained from participants' medical records. RESULTS: Visceral adipocyte size in the Child-Young group was the smallest of all the groups. Age affected visceral infiltration of M1-like cells with greater percent of M1-like cells in the Adult-Old and Child-Old groups. Though not significant, a stepwise increase in M2-like macrophages in VAT was observed with Adult-Young having the smallest followed by Adult-Old, Child-Young, and Child-Old having the greatest percent of M2-like macrophages. Pericellular fibrosis accumulation in SAT and VAT varied with both age and onset, particularly in the Child-Old group, which had the lowest fibrosis levels. Markers of cardiometabolic health (fasting glucose, glycated hemoglobin, total, HDL- and LDL-cholesterol and triglyceride concentrations) were positively and well-associated with adipose tissue characteristics of the Child-Old group but not of the Adult-Young group. CONCLUSION: Older adults with childhood-onset obesity, who had the greatest duration of obesity exposure, were particularly vulnerable to the cardiometabolic effects associated with perturbations in adipose tissue characteristics. These results suggest that age and age of obesity onset may have independent and cumulative effects on obesity pathology.

The association between midwifery staffing levels and the experiences of mothers on postnatal wards: Cross sectional analysis of routine data.

BACKGROUND: Women have consistently reported lower satisfaction with postnatal care compared with antenatal and labour care. The aim of this research was to examine whether women's experience of inpatient postnatal care in England is associated with variation in midwifery staffing levels. METHODS: Analysis of data from the National Maternity Survey in 2018 including 17,611 women from 129 organisations. This was linked to hospital midwifery staffing numbers from the National Health Service (NHS) Workforce Statistics and the number of births from Hospital Episode Statistics. A two-level logistic regression model was created to examine the association of midwifery staffing levels and experiences in post-natal care. RESULTS: The median Full Time Equivalent midwives per 100 births was 3.55 (interquartile range 3.26-3.78). Higher staffing levels were associated with less likelihood of women reporting delay in discharge (adjusted odds ratio [aOR] 0.849, 95% CI 0.753-0.959, p = 0.008), increased chances of women reporting that staff always helped in a reasonable time aOR1.200 (95% CI 1.052, 1.369, p = 0.007) and that they always had the information or explanations they needed aOR 1.150 (95% CI 1.040, 1.271, p = 0.006). Women were more likely to report being treated with kindness and understanding with higher staffing, but the difference was small and not statistically significant aOR 1.059 (0.949, 1.181, p = 0.306). CONCLUSIONS: Negative experiences for women on postnatal wards were more likely to occur in trusts with fewer midwives. Low staffing could be contributing to discharge delays and lack of support and information, which may in turn have implications for longer term outcomes for maternal and infant wellbeing.

Correlación entre la expresión del receptor dopaminérgico D2 y presencia de movimientos involuntarios anormales (MIA) en un modelo de disquinesia en ratas Wistar hemiparkinsonizadas / Correlation between dopamine receptor D2 expression and presence of abnormal involuntary movements in Wistar rats with hemiparkinsonism and dyskinesia

La enfermedad de Parkinson (EP) se caracteriza por una serie de deficiencias motoras que son tratadas comúnmente con L-DOPA; sin embargo, tras un uso crónico se desarrollan disquinesias inducidas por L-DOPA (DIL). Por otra parte, el origen de las DIL no está del todo claro, pero se asocia con alteración en receptores dopaminérgicos, donde los receptores D2 (RD2) han sido poco estudiados. El presente trabajo buscó: 1) desarrollar y estandarizar un modelo experimental de disquinesia con L-DOPA en ratas hemiparkinsonizadas, y 2) evaluar la correlación entre la expresión del RD2 y la manifestación de movimientos involuntarios anormales (MIA). Se utilizaron 21 ratas Wistar macho asignadas a 3 grupos: control intacto, lesionados (con la neurotoxina 6-OHDA) y lesionados disquinéticos (inyectados con L-DOPA durante 19 días). Los reactivos biológicos se sometieron a pruebas comportamentales para evaluar el deterioro sensoriomotor. Los animales del grupo disquinético desarrollaron de forma gradual MIA durante el tratamiento, siendo mayores los MIA de miembro anterior y menores los de tipo locomotor (p < 0,05). Todos los MIA fueron significativamente evidentes a partir del día 5 y se mantuvieron hasta el último día de inyección. Además, se pudo evidenciar incremento en la densidad del RD2 en el estriado y el cerebro anterior medial en los grupos lesionados con respecto al control, así como también una posible asociación entre la expresión del RD2 y MIA de tipo locomotor. Por lo que concluimos que el RD2 está implicado en el fenómeno disquinético generado con la L-DOPA. (AU)

Parkinson's disease (PD) is characterised by motor alterations, which are commonly treated with L-DOPA. However, long-term L-DOPA use may cause dyskinesia. Although the pathogenic mechanism of L-DOPA-induced dyskinesia is unclear, the condition has been associated with alterations in dopamine receptors, among which D2 receptors (D2R) have received little attention. This study aims to: (i) develop and standardise an experimental model of L-DOPA-induced dyskinesia in rats with hemiparkinsonism; and (ii) evaluate the correlation between D2R expression and presence of abnormal involuntary movements (AIM). We allocated 21 male Wistar rats into 3 groups: intact controls, lesioned rats (with neurotoxin 6-OHDA), and dyskinetic rats (injected with L-DOPA for 19 days). Sensorimotor impairment was assessed with behavioural tests. Dyskinetic rats gradually developed AIMs during the treatment period; front leg AIMs were more severe and locomotor AIMs less severe (P < .05). All AIMs were significantly evident from day 5 and persisted until the last day of injection. D2R density was greater in the striatum and the medial anterior brain of the lesioned and dyskinetic rats than in those of controls. Our results suggest an association between D2R expression and locomotor AIMs. We conclude that RD2 is involved in L-DOPA-induced dyskinesia. (AU)

Bio-processing of macroalgae Palmaria palmata: metabolite fractionation from pressed fresh material and ensiling considerations for long-term storage.

Red algae, belonging to the phylum Rhodophyta, contain an abundance of useful chemicals including bioactive molecules and present opportunities for the production of different products through biorefinery cascades. The rhodophyte Palmaria palmata, commonly termed dulse or dillisk, grows predominantly on the northern coasts of the Atlantic and Pacific Oceans and is a well-known snack food. Due to its abundance, availability and cultivation capacity, P. palmata was selected for study as a potential candidate for a biorefinery process. In addition to studying juice and solid fractions of freshly harvested P. palmata, we have investigated the novel possibility of preserving algal biomass by ensilaging protocols similar to those employed for terrestrial forage crops. In the metabolite partitioning within the solid and liquid fractions following screw-pressing, the majority of the metabolites screened for-water soluble carbohydrates, proteins and amino acids, lipids, pigments, phenolics and antioxidant activity-remained in the solid fraction, though at differing proportions depending on the metabolite, from 70.8% soluble amino acids to 98.2% chlorophyll a and 98.1% total carotenoids. For the ensiling study, screw-pressed P. palmata, with comparative wilted and chopped, and chopped only samples, were ensiled at scale with and without Safesil silage additive. All samples were successfully ensiled after 90 days, with screw-pressing giving lower or equal pH before and after ensiling compared with the other preparations. Of particular note was the effluent volumes generated during ensiling: 26-49% of the fresh weight, containing 16-34% of the silage dry matter. This may be of advantage depending on the final use of the biomass.

Rapid detection and differentiation of mobile colistin resistance (mcr-1 to mcr-10) genes by real-time PCR and melt-curve analysis.

BACKGROUND: The emergence of multi-drug-resistant (MDR) micro-organisms prompted new interest in older antibiotics, such as colistin, that had been abandoned previously due to limited efficacy or high toxicity. Over the years, several chromosomal-encoded colistin resistance mechanisms have been described; more recently, 10 plasmid-mediated mobile colistin resistance (mcr) genes have been identified. Spread of these genes among MDR Gram-negative bacteria is a matter of serious concern; therefore, reliable and timely mcr detection is paramount. AIM: To design and validate a multiplex real-time polymerase chain reaction (PCR) assay for detection and differentiation of mcr genes. METHODS: All available mcr alleles were downloaded from the National Center for Biotechnology Information Reference Gene Catalogue, aligned with Clustal Omega and primers designed using Primer-BLAST. Real-time PCR monoplexes were optimized and validated using a panel of 120 characterized Gram-negative strains carrying a wide range of resistance genes, often in combination. Melt-curve analysis was used to confirm positive results. FINDINGS: In-silico analysis enabled the design of a 'screening' assay for detection of mcr-1/2/6, mcr-3, mcr-4, mcr-5, mcr-7, mcr-8 and mcr-9/10, paired with an internal control assay to discount inhibition. A 'supplementary' assay was subsequently designed to differentiate mcr-1, mcr-2, mcr-6, mcr-9 and mcr-10. Expected results were obtained for all strains (100% sensitivity and specificity). Melt-curve analysis showed consistent melting temperature results. Inhibition was not observed. CONCLUSIONS: The assay is rapid and easy to perform, enabling unequivocal mcr detection and differentiation even when more than one variant is present. Adoption by clinical and veterinary microbiology laboratories would aid the surveillance of mcr genes amongst Gram-negative bacteria.

Correlation between dopamine receptor D2 expression and presence of abnormal involuntary movements in Wistar rats with hemiparkinsonism and dyskinesia. / Correlación entre la expresión del receptor dopaminérgico D2 y presencia de movimientos involuntarios anormales (MIA) en un modelo de disquinesia en ratas Wistar hemiparkinsonizadas.

Parkinson's disease (PD) is characterised by motor alterations, which are commonly treated with L-DOPA. However, long-term L-DOPA use may cause dyskinesia. Although the pathogenic mechanism of L-DOPA-induced dyskinesia is unclear, the condition has been associated with alterations in dopamine receptors, among which D2 receptors (D2R) have received little attention. This study aims to: (i)develop and standardise an experimental model of L-DOPA-induced dyskinesia in rats with hemiparkinsonism; and (ii)evaluate the correlation between D2R expression and presence of abnormal involuntary movements (AIM). We allocated 21 male Wistar rats into 3 groups: intact controls, lesioned rats (with neurotoxin 6-OHDA), and dyskinetic rats (injected with L-DOPA for 19 days). Sensorimotor impairment was assessed with behavioural tests. Dyskinetic rats gradually developed AIMs during the treatment period; front leg AIMs were more severe and locomotor AIMs less severe (P<.05). All AIMs were significantly evident from day 5 and persisted until the last day of injection. D2R density was greater in the striatum and the medial anterior brain of the lesioned and dyskinetic rats than in those of controls. Our results suggest an association between D2R expression and locomotor AIMs. We conclude that RD2 is involved in L-DOPA-induced dyskinesia.

"There's always something else": Patient perspectives on improving the implementation of obesity guidelines in general practice.

OBJECTIVES: The prevalence of obesity in Australia is rising. National guidelines for the management of overweight and obesity exist but our previous work demonstrates poor implementation of key elements in general practice. The aim of this study was to describe patient perspectives on the implementation of obesity guidelines in general practice. METHODS: Qualitative study of 40 people living with obesity (PwO) who were recruited through general practices in Melbourne, Australia. PwO had a recorded BMI in the overweight range or above (>25), had attended a consultation in the last 6 months and had a diagnosis of at least one of the following: diabetes, kidney disease, hyperlipidemia, hypertension, or cardiovascular disease. Semi-structured telephone interviews were conducted with patients. Interviews were audio-recorded, transcribed verbatim and analysed thematically. RESULTS: While a strong general practitioner (GP)-patient relationship enabled conversation to occur about weight management there was uncertainty as to whether patients or GPs should broach the topic of weight. Patients described complacency regarding their weight and often being unprepared to take up GP advice. Other health issues were felt to take precedence, and patients described inconsistent provision of information and resources to assist them in tackling their weight problems. CONCLUSIONS: It is imperative to take into account patient perspectives on obesity management in general practice in order to improve health outcomes. This study provides valuable insights into how PwO can be better managed. Interventions should also include strategies to help patients maintain motivation in making lifestyle changes to support healthy weight loss.

"Bridging, brokering, and buffering": a theoretical exploration of school leaders' engagement with local school wellness policy implementation.

BACKGROUND: The Healthy, Hunger-Free Kids Act of 2010 (P.L. 111-296) prompted the expansion of federal requirements for local school wellness policies, which aim to improve health promoting practices across school districts in the USA. This qualitative study examined how school district superintendents-as key school leaders who are often listed as the district accountability figure for wellness policies applicable to kindergarten through 12th grade-engaged with wellness policy implementation. The inquiry was guided by evidence-informed implementation and leadership frameworks, including the Consolidated Framework for Implementation Research (CFIR) and "bridging, buffering, and brokering" strategies from education leadership theory. METHODS: We conducted focus groups and interviews with superintendents (n = 39) from 23 states. Interviews were recorded and professionally transcribed; transcripts were team-coded in Atlas.ti v8 using an iteratively revised coding guide that was informed by CFIR, pilot testing, and during weekly analyst meetings. Principles of constant comparative analysis were employed to develop themes. RESULTS: Most superintendents' reported positive perspectives and personal motivations to engage with wellness policy implementation. Within the CFIR process domain, superintendents demonstrated adaptive leadership traits and employed a combination of "bridging, buffering, and brokering" strategies to lead implementation activities. Rather than focus on personal traits, an emphasis on specific strategies highlights actions that may be applied. CONCLUSIONS: The findings offer practical strategies to support superintendents with implementation, as well as a formative contribution to the dearth of theoretical frameworks in school wellness literature, particularly by advancing the specific understanding of leadership roles within a broader implementation framework. The application of education theory allowed for a deeper inquiry into the potential ways that leaders' strategies and engagement influences implementation more broadly.

Artificial Synthesis of Conjugated Microporous Polymers via Sonogashira-Hagihara Coupling.

Amorphous network materials are becoming increasingly important with applications, for example, as supercapacitors, battery anodes, and proton conduction membranes. The design of these materials is hampered by the amorphous nature of the structure and sensitivity to synthetic conditions. Here, we show that through artificial synthesis, fully mimicking the catalytic formation cycle, and full synthetic conditions, we can generate structural models that can fully describe the physical properties of these amorphous network materials. This opens up pathways for the rational design where complex structural influences, such as the solvent and catalyst choice, can be taken into account.

Dynamics of PfEMP1 Antibody Profile From Birth to 12 Months of Age in Beninese Infants.

BACKGROUND: Plasmodium falciparum-infected erythrocytes bind to specific endothelial cell receptors via members of the PfEMP1 family exported onto the erythrocyte surface. These interactions are mediated by different types of cysteine-rich interdomain region (CIDR) domains found in the N-terminal region of all PfEMP1. CIDRα1 domains bind endothelial protein C receptor (EPCR), CIDRα2-6 domains bind CD36, whereas the receptor specificity of CIDRß/γ/δ domains is unknown. METHODS: In this study, we investigated the level of immunoglobulin (Ig)G targeting the different types of PfEMP1 CIDR during the first year of life. We used plasma collected longitudinally from children of pregnant women who had been followed closely through pregnancy. RESULTS: Antibodies to CIDRα1 domains were more frequent in cord blood compared with antibodies to CIDRα2-6 domains. Higher IgG levels to EPCR-binding CIDRα1 variants positively correlated with the timing of first infections. Antibodies to all PfEMP1 types declined at similar rates to the point of disappearance over the first 6 months of life. At 12 months, children had acquired antibody to all types of CIDR domains, mostly in children with documented P falciparum infections. CONCLUSIONS: These observations agree with the notion that the timing and phenotype of first P falciparum infections in life are influenced by the immune status of the mother.

"90% of the time, it's not just weight": General practitioner and practice staff perspectives regarding the barriers and enablers to obesity guideline implementation.

OBJECTIVE: To identify the views of GPs and general practice staff regarding barriers and enablers to implementation of obesity guideline recommendations in general practice. METHODS: Twenty general practitioners (GPs) and 18 practice staff from inner-eastern Melbourne, Australia, participated in semi-structured telephone interviews. The interview schedule was informed by the Theoretical Domains Framework (TDF). Interviews were audio-recorded, transcribed verbatim and underwent thematic analysis. RESULTS: Participants lacked familiarity with and knowledge of the NHMRC obesity guidelines. Barriers and enablers were predominantly related to five theoretical domains: (1) environmental context and resources, (2) knowledge, (3) emotion, (4) beliefs about consequences, and (5) motivation and goals. Time pressures in consultations, costs for the patient, reluctance to add to patient burden particularly in those with comorbidities such as mental health issues, lack of awareness about services to refer patients to and GPs' fear of embarrassing patients and losing them were significant barriers. Enablers included having a strong doctor-patient relationship and a sense of responsibility to the patient to address weight. CONCLUSIONS: Obesity guidelines and policy makers need to better engage with issues of multimorbidity, socioeconomic disadvantage and workforce issues if recommendations are to be widely adopted in general practice. Tasksharing, teamwork and technology are potential solutions to some of the barriers. Patient perspectives and approaches to being able to overcome stigma and legitimise obesity management in primary care consultations could also assist.

Major risk factors for sexual minority young people's mental and physical health: findings from a county-wide school-based health needs assessment.

BACKGROUND: Childhood health is an important adult health predictor. Sexual orientation is increasingly recognized as influential on children and young people's (CYP) mental and physical health. METHODS: Data came from a cross-sectional survey of year 9 children attending schools in two local authorities in the north-west of England, including mental and physical health indicators, and demographic characteristics including sexual orientation. The sample of 8058 represented 67.8% of the eligible population. Data were analysed by sexual orientation, sexual majority or sexual minority. RESULTS: Children reporting their sexual orientation as sexual minority reported worse mental and physical health outcomes and behaviours than sexual majority peers; had higher odds of being lonely (odds ratios (OR) = 8.24, 95% C.I.: 6.56-10.37), having self-harmed (OR = 7.28, 95% C.I.: 5.78-9.15), being bullied (OR = 4.76, 95% C.I.: 3.74-6.05) or perceiving themselves as overweight (OR = 2.40, 95% C.I.: 1.89-3.06). CONCLUSIONS: It is important to identify and support children in a sexual minority. Research is required to understand differences between children within sexual minorities and the impact on outcomes and rights. Health and social policy and services, should respond to the vulnerabilities of sexual minority CYP.

Lactobacillus rhamnosus LRB mediated inhibition of oral streptococci.

Lactobacillus rhamnosus is a lactic acid bacterium with a diverse ecological habitat. We recently isolated a L. rhamnosus strain (LRB) from a healthy baby-tooth that had naturally fallen out. We determined the whole genome sequence of LRB and found that the isolate is closely genetically related to an intestinal isolate, L. rhamnosus GG (ATCC 53103). However, the LRB genome had lost about a 75-kb segment and undergone a genomic rearrangement. We assessed LRB's capacity to survive in the gut environment, at least temporarily. We found that LRB, like the intestinal isolate ATCC 53103, showed resistance to low pH but sensitive to bile salt. Surprisingly, we found that this oral isolate LRB showed strong antimicrobial activity against a variety of oral streptococci including Streptococcus mutans. The production of antimicrobial activity is dependent on media composition since some media supported the production while others did not. The production of antimicrobial activity is also dependent on growth temperature, with optimal production at 37°C. The antimicrobial activity was not restricted to streptococci, but effective against a variety of organisms, including ESKAPE pathogens.

Zoonotic Transfer of Clostridium difficile Harboring Antimicrobial Resistance between Farm Animals and Humans.

The emergence of Clostridium difficile as a significant human diarrheal pathogen is associated with the production of highly transmissible spores and the acquisition of antimicrobial resistance genes (ARGs) and virulence factors. Unlike the hospital-associated C. difficile RT027 lineage, the community-associated C. difficile RT078 lineage is isolated from both humans and farm animals; however, the geographical population structure and transmission networks remain unknown. Here, we applied whole-genome phylogenetic analysis of 248 C. difficile RT078 strains from 22 countries. Our results demonstrate limited geographical clustering for C. difficile RT078 and extensive coclustering of human and animal strains, thereby revealing a highly linked intercontinental transmission network between humans and animals. Comparative whole-genome analysis reveals indistinguishable accessory genomes between human and animal strains and a variety of antimicrobial resistance genes in the pangenome of C. difficile RT078. Thus, bidirectional spread of C. difficile RT078 between farm animals and humans may represent an unappreciated route disseminating antimicrobial resistance genes between humans and animals. These results highlight the importance of the "One Health" concept to monitor infectious disease emergence and the dissemination of antimicrobial resistance genes.

Endemic goitre and hypothyroidism in an adult female patient dependent on total parenteral nutrition.

We present the case of a thirty-year-old female patient who was referred to the endocrinology team with an enlarging goitre and biochemical hypothyroidism. She had been dependent on total parenteral nutrition for the previous six years as a result of intestinal failure thought to be caused by possible underlying mitochondrial disease. The patient also suffers from a Desmin myopathy, and at present, the exact aetiology behind her intestinal failure is not certain. The goitre was smooth and had been enlarging slowly over the previous few months. Thyroid peroxidase antibodies were found to be within normal range. Further analysis of the case showed that twelve months earlier the patients total parenteral nutrition (TPN) feed had been altered as a result of manganese toxicity. The current feeding regimen did not contain a trace element additive which had previously supplied iodine supplementation. A little detective work established that iodine content to the TPN had been reduced, the trace element additive (Additrace) was recommenced providing 1 µmol of iodine per day, equating to 130 µg of iodine. Following this change, thyroid-stimulating hormone levels returned to normal and the goitre quickly reduced in size. We present a rare case of endemic goitre and hypothyroidism in a patient receiving inadequate iodine supplementation through total parenteral nutrition. LEARNING POINTS: Endemic goitre and hypothyroidism secondary to iodine deficiency are rare in the developed world. However, the diagnosis should be considered in the setting of a diffuse goitre and negative thyroid antibodies.Although rare, endemic goitre should be considered in patients who present with hypothyroidism and who are dependent on total parenteral nutrition.Treatment with levothyroxine is not required in endemic goitre as thyroid function tests generally normalise with the addition of iodine to the diet/total parenteral nutrition regimen.Iodine supplementation at a level recommended by the European Society for Clinical Nutrition and Metabolism (ESPEN) was observed to quickly normalise this patient's thyroid function tests.

Pharmacokinetics of testosterone cream applied to scrotal skin.

Scrotal skin is thin and has high steroid permeability, but the pharmacokinetics of testosterone via the scrotal skin route has not been studied in detail. The aim of this study was to define the pharmacokinetics of testosterone delivered via the scrotal skin route. The study was a single-center, three-phase cross-over pharmacokinetic study of three single doses (12.5, 25, 50 mg) of testosterone cream administered in random sequence on different days with at least 2 days between doses to healthy eugonadal volunteers with endogenous testosterone suppressed by administration of nandrolone decanoate. Serum testosterone, DHT and estradiol concentrations were measured by liquid chromatograpy, mass spectrometry in extracts of serum taken before and for 16 h after administration of each of the three doses of testosterone cream to the scrotal skin. Testosterone administration onto the scrotal skin produced a swift (peak 1.9-2.8 h), dose-dependent (p < 0.0001) increase in serum testosterone with the 25 mg dose maintaining physiological levels for 16 h. Serum DHT displayed a time- (p < 0.0001), but not dose-dependent, increase in concentration reaching a peak concentration of 1.2 ng/mL (4.1 nm) at 4.9 h which was delayed by 2 h after peak serum testosterone. There were no significant changes in serum estradiol over time after testosterone administration. We conclude that testosterone administration to scrotal skin is well tolerated and produces dose-dependent peak serum testosterone concentration with a much lower dose relative to the non-scrotal transdermal route.

[Primary infection with cytomegalovirus: An infectious cause of splenic infarction]. / Primo-infection à cytomégalovirus : une cause infectieuse d'infarctus splénique.

INTRODUCTION: Cytomegalovirus-associated thrombosis has been extensively reported in the medical literature, mainly in immune-compromised patients. However, the association with splenic infarcts has rarely been reported. CASE REPORT: We report a 32-year-old Caucasian and immunocompetent woman who presented with a splenic infarction during a primary infection with CMV. The differential diagnostic ruled out embolic, hematologic, gastrointestinal and coagulation disorders. The outcome was favorable with symptomatic treatment. CONCLUSION: A primary infection with CMV must be added to the diagnostic work-up in the presence of a febrile splenic infarction, especially when it is associated with a biological mononucleosis reaction.