The Effect of Greater Area Deprivation and Medicaid Insurance Status on Timing of Care and Rate of Reinjury After Anterior Cruciate Ligament Reconstruction.

Background: Lower socioeconomic status and public insurance lead to a longer delay to surgery and a higher likelihood of concomitant pathology before undergoing anterior cruciate ligament reconstruction (ACLR). However, few studies have examined the influence of community deprivation on ACLR timing and outcomes. Purpose/Hypothesis: The primary aim of this study was to define the effect of the area deprivation index (ADI) and insurance classification on access to orthopaedic care after an ACL rupture, and the secondary aim was to determine whether these variables were associated with a second ACL injury after primary ACLR. It was hypothesized that patients with a greater national ADI percentile and Medicaid insurance would experience longer delays to care and an increased risk of reinjury after ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective study was performed to evaluate patients undergoing primary ACLR between 2016 and 2019. The national ADI percentile was obtained utilizing the Neighborhood Atlas website. The relationship between national ADI percentile and care characteristics (eg, time to specialized care) was investigated using the Spearman rho correlation coefficient (r). The association between patient and care characteristics and second ACL injury after the index procedure (ie, graft rerupture or contralateral ACL rupture) was investigated using binary logistic regression. Results: A total of 197 patients met the inclusion criteria. Longer times from injury to surgery (r = 0.238; P < .001) and from specialized care to surgery (r = 0.217; P = .002) were associated with a greater national ADI percentile. The second injury group reported significantly greater national ADI (P = .026) and included a greater percentage of patients with Medicaid insurance (31.3%) compared with the no second injury group. Patients experienced 5.1% greater odds of a second ACL injury for each additional month between evaluation and surgery. Conclusion: Greater national ADI percentile and Medicaid insurance status were associated with adverse ACLR timing and outcomes. Patients with a greater national ADI percentile took significantly longer to obtain surgery after ACL injury. Those who sustained a second ACL injury after ACLR had an overall higher mean national ADI percentile and included a greater proportion of patients with Medicaid compared with those who did not sustain a second ACL injury. Future studies should critically investigate the underlying factors of these associations to reach equity in orthopaedic care.

IMPROVE 2022 International Meeting on Pathway-Related Obesity: Vision of Excellence.

Nearly 90 clinicians and researchers from around the world attended the first IMPROVE 2022 International Meeting on Pathway-Related Obesity. Delegates attended in person or online from across Europe, Argentina and Israel to hear the latest scientific and clinical developments in hyperphagia and severe, early-onset obesity, and set out a vision of excellence for the future for improving the diagnosis, treatment, and care of patients with melanocortin-4 receptor (MC4R) pathway-related obesity. The meeting co-chair Peter Kühnen, Charité Universitätsmedizin Berlin, Germany, indicated that change was needed with the rapidly increasing prevalence of obesity and the associated complications to improve the understanding of the underlying mechanisms and acknowledge that monogenic forms of obesity can play an important role, providing insights that can be applied to a wider group of patients with obesity. World-leading experts presented the latest research and led discussions on the underlying science of obesity, diagnosis (including clinical and genetic approaches such as the role of defective MC4R signalling), and emerging clinical data and research with targeted pharmacological approaches. The aim of the meeting was to agree on the questions that needed to be addressed in future research and to ensure that optimised diagnostic work-up was used with new genetic testing tools becoming available. This should aid the planning of new evidence-based treatment strategies for the future, as explained by co-chair Martin Wabitsch, Ulm University Medical Center, Germany.

Short, frequent, light-intensity walking activity improves postprandial vascular-inflammatory biomarkers in people with type 1 diabetes: The SIT-LESS randomized controlled trial.

AIM: To examine the effect of interrupting prolonged sitting with short, frequent, light-intensity activity on postprandial cardiovascular markers in people with type 1 diabetes (T1D). MATERIALS AND METHODS: In a randomized crossover trial, 32 adults with T1D (mean ± SD age 28 ± 5 years, glycated haemoglobin 67.9 ± 12.6 mmol/mol, 17 women) completed two 7-h laboratory visits separated by >7 days. Participants either remained seated for 7 h (SIT) or interrupted sitting with 3-min bouts of self-paced walking at 30-min intervals commencing 1 h after each meal (SIT-LESS). Physical activity, insulin regimen, experimental start times, and meal consumption were standardized during each arm. Plasma levels of interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, plasminogen activator inhibitor (PAI)-1 and fibrinogen were sampled at baseline, 3.5 and 7 h, and assessed for within- and between-group effects using a repeated measures ANOVA. The estimated glucose disposal rate was used to determine the insulin resistance status. RESULTS: Vascular-inflammatory parameters were comparable between SIT and SIT-LESS at baseline (p > .05). TNF-α, IL-1ß, PAI-1 and fibrinogen increased over time under SIT, whereas these rises were attenuated under SIT-LESS (p < .001). Specifically, over the 7 h under SIT, postprandial increases were detected in TNF-α, IL-1ß, PAI-1 and fibrinogen (+67%, +49%, +49% and +62%, respectively; p < .001 for all). Conversely, the SIT-LESS group showed no change in IL-1ß (-9%; p > .50), whereas reductions were observed in TNF-α, PAI-1 and fibrinogen (-22%, -42% and -44%, respectively; p < .001 for all). The intervention showed enhanced effects in insulin-resistant individuals with T1D. CONCLUSIONS: Interrupting prolonged sitting with light-intensity activity ameliorates postprandial increases in vascular-inflammatory markers in T1D. TRIAL REGISTRATION: The trial was prospectively registered (ISRCTN13641847).

Ovarian non-gestational placental site trophoblastic tumor with lung metastasis: further evidence for a distinct category of trophoblastic neoplasm.

We previously described a series of cases which characterize a distinct group of primary ovarian placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT) as a non-gestational set consistent with germ cell type/origin. Here we report a new case of ovarian non-gestational PSTT. The patient was a 13 year-old young female admitted for a spontaneous pneumothorax of the left lung. The pathology of lung wedge excision specimen demonstrated metastatic PSTT and ovarian biopsy showed atypical intermediate trophoblastic proliferation which was found to be PSTT in the subsequent salpingo-oophorectomy specimen. In the ovary, the tumor was composed of singly dispersed or small clusters of predominantly mononuclear cells and rare multinucleated cells extensively infiltrating the ovarian parenchyma, tubal mucosa, and paraovarian/paratubal soft tissue. A minor component of mature cystic teratoma (less than 5% of total tumor volume) was present. Immunohistochemically, the neoplastic cells of main tumor were diffusely immunoreactive for hPL, Gata3 and AE1/AE3, and had only rare hCG-positive or p63-positive cells. The morphology and immunohistochemical results support a PSTT. Molecular genotyping revealed an identical genotype pattern between the normal lung tissue and the metastatic PSTT, indicating its non-gestational nature of germ cell type/origin. This case represents the first case of such tumor with distant (lung) metastasis. This case also provides further evidence to support our recommendation that primary ovarian non-gestational intermediate trophoblastic tumors of germ cell type/origin, including PSTT and ETT, should be formally recognized in classification systems.

Diet composition and energy intake in humans.

Absolute energy from fats and carbohydrates and the proportion of carbohydrates in the food supply have increased over 50 years. Dietary energy density (ED) is primarily decreased by the water and increased by the fat content of foods. Protein, carbohydrates and fat exert different effects on satiety or energy intake (EI) in the order protein > carbohydrates > fat. When the ED of different foods is equalized the differences between fat and carbohydrates are modest. Covertly increasing dietary ED with fat, carbohydrate or mixed macronutrients elevates EI, producing weight gain and vice versa. In more naturalistic situations where learning cues are intact, there appears to be greater compensation for the different ED of foods. There is considerable individual variability in response. Macronutrient-specific negative feedback models of EI regulation have limited capacity to explain how availability of cheap, highly palatable, readily assimilated, energy-dense foods lead to obesity in modern environments. Neuropsychological constructs including food reward (liking, wanting and learning), reactive and reflective decision making, in the context of asymmetric energy balance regulation, give more comprehensive explanations of how environmental superabundance of foods containing mixtures of readily assimilated fats and carbohydrates and caloric beverages elevate EI through combined hedonic, affective, cognitive and physiological mechanisms. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.

Evaluation of Wild Peanut Species and Their Allotetraploids for Resistance against Thrips and Thrips-Transmitted Tomato Spotted Wilt Orthotospovirus (TSWV).

Thrips-transmitted tomato spotted wilt orthotospovirus (TSWV) causes spotted wilt disease in peanut (Arachis hypogaea L.) and limits yield. Breeding programs have been developing TSWV-resistant cultivars, but availability of sources of resistance against TSWV in cultivated germplasm is extremely limited. Diploid wild Arachis species can serve as important sources of resistance, and despite ploidy barriers (cultivated peanut is tetraploid), their usage in breeding programs is now possible because of the knowledge and development of induced interspecific allotetraploid hybrids. This study screened 10 wild diploid Arachis and six induced allotetraploid genotypes via thrips-mediated TSWV transmission assays and thrips' feeding assays in the greenhouse. Three parameters were evaluated: percent TSWV infection, virus accumulation, and temporal severity of thrips feeding injury. Results indicated that the diploid A. stenosperma accession V10309 and its derivative-induced allotetraploid ValSten1 had the lowest TSWV infection incidences among the evaluated genotypes. Allotetraploid BatDur1 had the lowest thrips-inflicted damage at each week post thrips release, while diploid A. batizocoi accession K9484 and A. duranensis accession V14167 had reduced feeding damage one week post thrips release, and diploids A. valida accession GK30011 and A. batizocoi had reduced feeding damage three weeks post thrips releasethan the others. Overall, plausible TSWV resistance in diploid species and their allotetraploid hybrids was characterized by reduced percent TSWV infection, virus accumulation, and feeding severity. Furthermore, a few diploids and tetraploid hybrids displayed antibiosis against thrips. These results document evidence for resistance against TSWV and thrips in wild diploid Arachis species and peanut-compatible-induced allotetraploids.

Interrupting prolonged sitting with frequent short bouts of light-intensity activity in people with type 1 diabetes improves glycaemic control without increasing hypoglycaemia: The SIT-LESS randomised controlled trial.

AIM: To examine the impact of interrupting prolonged sitting with frequent short bouts of light-intensity activity on glycaemic control in people with type 1 diabetes (T1D). MATERIALS AND METHODS: In total, 32 inactive adults with T1D [aged 27.9 ± 4.7 years, 15 men, diabetes duration 16.0 ± 6.9 years and glycated haemoglobin 8.4 ± 1.4% (68 ± 2.3 mmol/mol)] underwent two 7-h experimental conditions in a randomised crossover fashion with >7-day washout consisting of: uninterrupted sitting (SIT), or, interrupted sitting with 3-min bouts of self-paced walking at 30-min intervals (SIT-LESS). Standardised mixed-macronutrient meals were administered 3.5 h apart during each condition. Blinded continuous glucose monitoring captured interstitial glucose responses during the 7-h experimental period and for a further 48-h under free-living conditions. RESULTS: SIT-LESS reduced total mean glucose (SIT 8.2 ± 2.6 vs. SIT-LESS 6.9 ± 1.7 mmol/L, p = .001) and increased time in range (3.9-10.0 mmol/L) by 13.7% (SIT 71.5 ± 9.5 vs. SIT-LESS 85.1 ± 7.1%, p = .002). Hyperglycaemia (>10.0 mmol/L) was reduced by 15.0% under SIT-LESS (SIT 24.2 ± 10.8 vs. SIT-LESS 9.2 ± 6.4%, p = .002), whereas hypoglycaemia exposure (<3.9 mmol/L) (SIT 4.6 ± 3.0 vs. SIT-LESS 6.0 ± 6.0%, p = .583) was comparable across conditions. SIT-LESS reduced glycaemic variability (coefficient of variation %) by 7.8% across the observation window (p = .021). These findings were consistent when assessing discrete time periods, with SIT-LESS improving experimental and free-living postprandial, whole-day and night-time glycaemic outcomes (p < .05). CONCLUSIONS: Interrupting prolonged sitting with frequent short bouts of light-intensity activity improves acute postprandial and 48-h glycaemia in adults with T1D. This pragmatic strategy is an efficacious approach to reducing sedentariness and increasing physical activity levels without increasing risk of hypoglycaemia in T1D.

Fat-free mass and resting metabolic rate are determinants of energy intake: implications for a theory of appetite control.

Any explanation of appetite control should contain a description of physiological processes that could contribute a drive to eat alongside those that inhibit eating. However, such an undertaking was largely neglected until 15 years ago when a series of independent research programmes investigated the physiological roles of body composition and appetite. These outcomes demonstrated that fat-free mass (FFM), but not fat mass, was positively associated with objectively measured meal size and energy intake (EI). These findings have been accompanied by demonstrations that resting metabolic rate (RMR) is also positively associated with EI, with the influence of FFM largely mediated by RMR. These findings re-introduce the role of drive into models of appetite control and indicate how this can be integrated with processes of inhibition. The determinants of EI fit into an evolutionary perspective in which the energy demands of high metabolic rate organs and skeletal tissue constitute a need state underlying a tonic drive to eat. This approach should lead to the development of integrated models of appetite that include components of body composition (FFM) and energy expenditure (RMR) as tonic biological signals of appetite alongside other traditional tonic (adipose tissue derived) and episodic signals (gastrointestinal tract derived). This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

The importance of fat-free mass and constituent tissue-organs in the control of human appetite.

PURPOSE OF REVIEW: Traditional models of human appetite focus on the contribution of adipose tissue and the gastrointestinal tract, both of which exert mainly inhibitory influences. The purpose of this review is to consider the biological factors that influence the drive to eat. RECENT FINDINGS: Fat-free mass is positively associated with objectively measured meal size and daily energy intake. These findings have been replicated in multiple populations across the life-course in laboratory and free-living studies. Studies have shown that the effect of fat-free mass is statistically mediated by resting metabolic rate, suggesting that energy expenditure per se may influence energy intake. A recent MRI study has reported that fasting hunger was associated with high metabolic rate organ (heart, liver, brain, kidneys) and skeletal muscle mass. Integrating measures of body composition at the tissue-organ level and markers of their metabolic function with appetitive measures could provide novel insight into the mechanisms that influence appetite. SUMMARY: These recent findings suggest that fat-free mass and resting metabolic rate are determinants of energy intake. Consideration of fat-free mass and energy expenditure as physiological sources of appetitive signals helps reconcile the mechanisms underpinning the inhibition of eating with those that drive eating.

PivNG primers and probes set used in the cobas omni Utility Channel is a reliable supplemental test for detection of Neisseria gonorrhoeae in oropharyngeal, urogenital and rectal specimens collected in cobas PCR Media.

OBJECTIVE: To evaluate the clinical performance of the novel PivNG primers and probes set (PivNG test) used in the cobas omni Utility Channel for supplemental testing of Neisseria gonorrhoeae (NG). METHODS: Oropharyngeal, urogenital and rectal samples were self-collected during routine testing at Barts Health sexual health clinics, London, UK. Samples were tested by the cobas CT/NG test and PivNG cobas omni Utility Channel test on cobas 6800/8800 Systems. Supplemental testing was carried out with the Xpert CT/NG test. PivNG overall percent agreements, positive percent agreements (PPAs)/negative percent agreements (NPAs) and positive/negative predictive values were calculated for each sample type. Microscopy and/or culture data were included for a randomised subset of concordant/discordant results, and a composite reference standard (cobas CT/NG, Xpert CT/NG and culture results) adjusted for partial verification bias was used to determine PivNG PPA and NPA. RESULTS: Of 447 evaluable samples with valid results from all three assays (cobas CT/NG, PivNG and Xpert CT/NG), 288 (64.4%) were NG-positive by both PivNG and cobas CT/NG; 117 (26.2%) were NG-negative in both tests; and 42 (9.4%) had discordant results (with NG-negative supplementary Xpert) CT/NG results in 40/42 instances). Of 19 PivNG/Xpert CT/NG-discordant samples, 11 were confirmed NG-positive by microscopy and/or culture results. PivNG PPA and NPA were 100% and 91% for oropharyngeal swabs, 100% and 100% for vaginal swabs, 100% and 100% for male urine samples, and 100% and 97% for rectal swabs, respectively, compared with the partially adjusted composite reference standard. CONCLUSIONS: PivNG is a reliable supplementary test with high sensitivity for confirming NG infection when used in conjunction with the cobas CT/NG test and samples collected in cobas PCR Media. Moreover, the PivNG test offers a convenient, high-throughput solution for supplemental NG testing of various sample types, with the potential to reduce the number of indeterminate reports.

Solving the conundrum of intra-specific variation in metabolic rate: A multidisciplinary conceptual and methodological toolkit: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species.

Researchers from diverse disciplines, including organismal and cellular physiology, sports science, human nutrition, evolution and ecology, have sought to understand the causes and consequences of the surprising variation in metabolic rate found among and within individual animals of the same species. Research in this area has been hampered by differences in approach, terminology and methodology, and the context in which measurements are made. Recent advances provide important opportunities to identify and address the key questions in the field. By bringing together researchers from different areas of biology and biomedicine, we describe and evaluate these developments and the insights they could yield, highlighting the need for more standardisation across disciplines. We conclude with a list of important questions that can now be addressed by developing a common conceptual and methodological toolkit for studies on metabolic variation in animals.

Barriers to Exercise in Adults With Type 1 Diabetes and Insulin Resistance.

OBJECTIVE: Our aim in this study was to assess attitudes toward exercise and quality of life (QoL) in adults with type 1 diabetes (T1D) with and without insulin resistance (IR). METHODS: We pooled baseline pretreatment data from a subset of individuals with T1D from 2 randomized controlled trials. Estimated glucose disposal rate (eGDR), a validated surrogate marker of IR, was calculated using an established formula to classify individuals according to IR status with a cutpoint of <6 mg/kg/min for the determination of IR. Self-reported barriers to exercise were obtained using a validated questionnaire, the Barriers to Physical Activity in T1D (BAPAD-1). In addition, QoL was determined using the 36-item Short Form (SF-36) questionnaire. Differences between dichotomized variables were assessed using the independent t test, Mann-Whitney U test, or Fisher exact test. Linear regression was employed to explore the association of eGDR with BAPAD-1 and QoL scores, with sequential adjustment for potential confounders. RESULTS: Of the 85 individuals included in our study, 39 were classified as having IR. The mean BAPAD-1 total score was higher for individuals with IR (IR: 3.87±0.61; non-IR: 2.83±0.55; p<0.001). The highest exercise barrier scores for individuals with IR were risk of hypoglycemia (5.67±1.26) and risk of hyperglycemia (5.23±1.20), whereas the highest scoring exercise barrier scores for non-IR individuals were not diabetes-related, with low level of fitness (3.91±1.26) and physical health status, excluding diabetes (3.67±1.48), ranked highest. QoL scores were comparable between groups (p>0.05). CONCLUSIONS: Risk of hypoglycemia was the greatest barrier to exercise in individuals with T1D with IR, whereas non-diabetes-related barriers to exercise were more salient in individuals with T1D without IR.

Reducing Sitting Time in Type 1 Diabetes: Considerations and Implications.

Sedentary behaviours are ubiquitous in modern society, with Western populations spending approximately 50% of their waking hours in low levels of energy expenditure. This behaviour is associated with cardiometabolic derangements and increased morbidity and mortality. In individuals living with or at risk of developing type 2 diabetes (T2D), "breaking up" sedentariness by interrupting prolonged periods of sitting has been shown to acutely improve glucose management and cardiometabolic risk factors related to diabetes complications. As such, current guidelines recommend interrupting prolonged periods of sitting with short, frequent activity breaks. However, the evidence underpinning these recommendations remains preliminary and is focussed on those with or at risk of developing T2D, with little information regarding whether and how reducing sedentariness may be effective and safe in those living with type 1 diabetes (T1D). In this review, we discuss the potential application of interventions that target prolonged sitting time in T2D within the context of T1D.

HTLV seroprevalence in people using HIV pre-exposure prophylaxis in England.

OBJECTIVES: HTLV-1 is predominantly a sexually-transmitted infection but testing is not mentioned in HIV-PrEP guidelines. We ascertained HTLV-1/HTLV-2 seroprevalence amongst HIV-PrEP users in England. METHODS: An unlinked anonymous seroprevalence study. RESULTS: Amongst 2015 HIV-PrEP users, 95% were men, 76% of white ethnicity and 83% had been born in Europe. There were no HTLV-1/HTLV-2 seropositive cases (95% confidence interval 0% - 0.18%). CONCLUSIONS: There were no HTLV positive cases, likely reflecting the demographic of mostly white and European-born individuals. Similar studies are needed worldwide to inform public health recommendations for HIV-PrEP using populations, particularly in HTLV-endemic settings.

Do eating behavior traits predict energy intake and body mass index? A systematic review and meta-analysis.

At present, it is unclear whether eating behavior traits (EBT) predict objectively measured short-term energy intake (EI) and longer-term energy balance as estimated by body mass index (BMI). This systematic review examined the impact of EBT on BMI and laboratory-based measures of EI in adults ( ≥ 18 years) in any BMI category, excluding self-report measures of EI. Articles were searched up until 28th October 2021 using MEDLINE, PsycINFO, EMBASE and Web of Science. Sixteen EBT were identified and the association between 10 EBT, EI and BMI were assessed using a random-effects meta-analysis. Other EBT outcomes were synthesized qualitatively. Risk of bias was assessed with the mixed methods appraisal tool. A total of 83 studies were included (mean BMI = 25.20 kg/m2 , mean age = 27 years and mean sample size = 70). Study quality was rated moderately high overall, with some concerns in sampling strategy and statistical analyses. Susceptibility to hunger (n = 6) and binge eating (n = 7) were the strongest predictors of EI. Disinhibition (n = 8) was the strongest predictor of BMI. Overall, EBT may be useful as phenotypic markers of susceptibility to overconsume or develop obesity (PROSPERO: CRD42021288694).

Transformer Neural Networks for Protein Family and Interaction Prediction Tasks.

The scientific community is rapidly generating protein sequence information, but only a fraction of these proteins can be experimentally characterized. While promising deep learning approaches for protein prediction tasks have emerged, they have computational limitations or are designed to solve a specific task. We present a Transformer neural network that pre-trains task-agnostic sequence representations. This model is fine-tuned to solve two different protein prediction tasks: protein family classification and protein interaction prediction. Our method is comparable to existing state-of-the-art approaches for protein family classification while being much more general than other architectures. Further, our method outperforms other approaches for protein interaction prediction for two out of three different scenarios that we generated. These results offer a promising framework for fine-tuning the pre-trained sequence representations for other protein prediction tasks.

Molecular Analysis of HPV-independent Primary Endometrial Squamous Cell Carcinoma Reveals TP53 and CDKN2A Comutations : A Clinicopathologic Analysis With Re-evaluation of Diagnostic Criteria.

Human papillomavirus (HPV)-independent primary endometrial squamous cell carcinoma (PESCC) is a rare but aggressive subtype of endometrial carcinoma for which little is known about the genomic characteristics. Traditional criteria have restricted the diagnosis of PESCC to cases without any cervical involvement. However, given that modern ancillary techniques can detect HPV and characteristic genetic alterations that should identify the more common mimics in the differential diagnosis, including endometrial endometrioid carcinoma with extensive squamous differentiation and HPV-associated primary cervical squamous cell carcinoma, those criteria may benefit from revision. To further characterize PESCC, we identified 5 cases of pure squamous cell carcinoma dominantly involving the endometrium that had the potential to be PESCC: 1 case involving only the endometrium and 4 cases with some involvement of the cervix. Clinicopathologic features were assessed and immunohistochemical analysis (p16, estrogen receptor, progesterone receptor, and p53), HPV RNA in situ hybridization (high-risk and low-risk cocktails and targeted probes for 16 and 18), and molecular studies were performed. All tumors showed aberrant/mutation-type p53 expression, were negative for estrogen receptor, progesterone receptor, and p16, and had no detectable HPV. Per whole-exome sequencing, 4 of the 5 tumors demonstrated comutations in TP53 and CDKN2A (p16). Four patients died of disease within 20 months (range, 1 to 20 mo; mean, 9 mo), and 1 patient had no evidence of disease at 38 months. PESCC represents a unique, clinically aggressive subtype of endometrial cancer with TP53 and CDKN2A comutations. This characteristic profile, which is similar to HPV-independent squamous cell carcinoma of the vulva, is distinct from endometrioid carcinoma with extensive squamous differentiation and HPV-associated primary cervical squamous cell carcinoma and can be used to distinguish PESCC from those mimics even when cervical involvement is present. Diagnostic criteria for PESCC should be relaxed to allow for cervical involvement when other pathologic features are consistent with, and ancillary techniques are supportive of classification as such.

Norovirus attribution study: Detection of norovirus from the commercial food preparation environment in outbreak and non-outbreak premises.

AIMS: Norovirus remains the most significant virological risk that is transmitted via food and the environment to cause acute gastroenteritis. This study aimed to investigate the hypothesis that the contamination of the commercial food production environment with norovirus will be higher in premises that have recently reported a foodborne norovirus outbreak than those that have not. METHODS: Sampling of commercial food production environments was carried out across a 16-month period between January 2015 and April 2016 in the South East and the North West of England by local authority environmental health departments as part of routine surveillance visits to premises. A total of 2982 samples, 2038 virological and 944 bacteriological, were collected from 256 premises. Sixteen of these premises, six from South East and ten from North West England, were sampled as part of a public health outbreak investigation. RESULTS & CONCLUSIONS: Overall, 2038 swabs were submitted for norovirus testing, with an average of eight swabs per premises (range 4 to 23) and a median of seven. Of the premises sampled, 11.7% (30/256) yielded at least one norovirus-positive sample (environmental, and/or food handler hand swab), and 2.5% of the swabs were positive for norovirus. A peak in the positivity rate was seen in the South East in April 2016. No associations were found between norovirus positivity and bacteriology indicators, or between bacteriology indicators and hygiene ratings. SIGNIFICANCE AND IMPACT OF STUDY: This study demonstrates that food premises and food handlers remain a potential source of norovirus transmission and outbreaks.

Improving the accuracy of clinical interpretation of serological testing for the diagnosis of acute hepatitis a infection.

BACKGROUND: Hepatitis A (HA) remains a common infection globally that results in a self-limiting hepatitis with gastrointestinal and systemic symptoms. Direct detection of the virus in blood or stool is often not possible once symptomatic. Serological testing is frequently performed to investigate abnormal liver function tests - and interpretation of equivocal and low-level positive anti-hepatitis A virus (HAV) IgM is difficult even in the context of accurate epidemiological and clinical information. OBJECTIVES: The aim of this project was to characterise the association between low-level reactive anti-HAV IgM results and clinical disease. STUDY DESIGN: Anti-HAV serology results recorded over 22 months were analysed. Equivocal and positive Architect anti-HAV IgM results were matched with available clinical and demographical data to identify confirmed and probable cases of acute HAV infection. RESULTS: Reactive anti-HAV IgM results were recorded for 88/7661 (1.15%) samples. Using clinical and laboratory data, 35 patients were confirmed to have acute HAV infection. Acute HA was associated with a mean Architect anti-HAV IgM value of 9.4 (SD 6.8-12.0). Cases of HA had a mean peak ALT value of 1920 (SD 682-3158). All confirmed cases (35/35) of acute HAV were associated with at least one clinical indicator, with 28/31 cases (90%) having a documented jaundice. All 35 (100%) cases of acute HAV infection had anti-HAV IgM > 4.0. A diagnosis other than acute HA was identified in 7/11 (63.6%) of low-level reactive anti-HAV IgM results (clinical data unavailable for further 4/11, 36.3%). Where clinical information was available, acute HA was excluded in all 31 patients with equivocal or low-level reactive anti-HAV IgM results. CONCLUSIONS: The accuracy of reports sent out to the clinician showed room for improvement. An interpretive algorithm is proposed including a clinically significant cut-off value for anti-HAV IgM.