Impact of the coronavirus disease 2019 (COVID-19) pandemic on the presentation of paediatric acute appendicitis: an observational study.

AIM: To determine whether there were differences in the clinical presentation of patients imaged to evaluate for acute appendicitis in 2020 compared to 2019 with the hope that this information might better identify patients who should undergo imaging work-up and those who should not. MATERIALS AND METHODS: This retrospective observational study included patients <18 years who were evaluated for appendicitis between 1 March and 31 May 2019 and 2020. A total of 465 patients were stratified by final diagnosis (appendicitis versus not appendicitis) and compared based on presenting symptoms, physical examination findings, vital signs, and laboratory test results. RESULTS: Symptoms and physical examination findings that were significant in the positive cohort in both years included right lower quadrant pain, pain with movement, migration of pain, right lower quadrant tenderness, and peritoneal findings. Reporting upper respiratory symptoms was an independent predictor of negative results among all patients and in 2019. Both negative cohorts were more likely to have negative physical examinations. Anorexia and nausea/vomiting were more likely among positive cases in 2019 whereas diarrhoea was more likely among positive cases in 2020. CONCLUSIONS: The COVID-19 pandemic did not significantly change the presenting features of acute appendicitis. The results of the present study emphasise the importance of the physical examination. The ambiguity of symptoms that mimic gastroenteritis justifies imaging in these patients.

Efficacy of color lenses in abolishing photosensitivity: Beyond the one-type-fits-all approach?

OBJECTIVE: Red-light filtering lenses represent an additional option to medication in photosensitive epilepsy. Blue lenses (Clarlet Z1 F133) can dramatically reduce seizure frequency, with a substantial restriction in luminance that can limit their applicability in daily life. We investigated the efficacy of 4 blue lenses with higher transmittance and reduced chromatic distortion in abolishing the photoparoxysmal EEG response (PPR) compared to the gold-standard Z1 lenses. METHODS: We reviewed EEG data during photic-and pattern stimulation in 19 consecutive patients (6-39 years) with photosensitivity (PS). Stimulation was performed at baseline and while wearing Z1 and the four new lenses. Lenses were tested in the same session by asking the patient to wear them in a sequentially randomized fashion while stimulating again with the most provocative photic/pattern stimuli. The primary outcome was the change in the initial PPR observed for each lens, categorized as no change, reduction, and abolition. RESULTS: Photosensitivity was detected in 17 subjects (89.5%); pattern sensitivity (PtS) was identified in 14 patients (73.7%). The highest percentages of PPR abolition/reduction were observed with Z1, for both PS and PtS. Regarding the new lenses, B1 + G1 offered the best rates, followed by B1 + G2. B1 + G3 and B1 showed lower efficacy rates, particularly for PtS. In the comparative analysis, no significant differences in PPR suppression were detected between the five lenses for PS. For PtS, the capacity of Z1 for PPR abolition was significantly higher compared with B1 + G3 and B1. CONCLUSIONS: This preliminary study suggests efficacy of the new group of blue lenses with potentially greater tolerability, particularly in regions with fewer sunlight hours during winter. In line with the current trend for personalized approach to treatment, this study suggests that in some patients there might be scope in extending the testing to offer the lens with the higher transmittance effective in abolishing the PPR.

Safety and efficacy of the selective progesterone receptor modulator asoprisnil for heavy menstrual bleeding with uterine fibroids: pooled analysis of two 12-month, placebo-controlled, randomized trials.

STUDY QUESTION: Can asoprisnil, a selective progesterone receptor modulator, provide clinically meaningful improvements in heavy menstrual bleeding (HMB) associated with uterine fibroids with an acceptable safety profile? SUMMARY ANSWER: Uninterrupted treatment with asoprisnil for 12 months effectively controlled HMB and reduced fibroid and uterine volume with few adverse events. WHAT IS KNOWN ALREADY: In a 3-month study, asoprisnil (5, 10 and 25 mg) suppressed uterine bleeding, reduced fibroid and uterine volume, and improved hematological parameters in a dose-dependent manner. STUDY DESIGN, SIZE, DURATION: In two Phase 3, double-blind, randomized, placebo-controlled, multicentre studies, women received oral asoprisnil 10 mg, asoprisnil 25 mg or placebo (2:2:1) once daily for up to 12 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: Premenopausal women ≥18 years of age in North America with HMB associated with uterine fibroids were included (N = 907). The primary efficacy endpoint was the percentage of women who met all three predefined criteria at 12 months or the final month for patients who prematurely discontinued: (1) ≥50% reduction in monthly blood loss (MBL) by menstrual pictogram, (2) hemoglobin concentration ≥11 g/dL or an increase of ≥1 g/dL, and (3) no interventional therapy for uterine fibroids. Secondary efficacy endpoints included changes in other menstrual bleeding parameters, volume of the largest fibroids, uterine volume and health-related quality of life (HRQL). MAIN RESULTS AND THE ROLE OF CHANCE: In all, 90% and 93% of women in the asoprisnil 10-mg and 25-mg groups, respectively, and 35% of women in the placebo group met the primary endpoint (P < 0.001). Similar results were observed at month 6 (P < 0.001). The percentage of women who achieved amenorrhea in any specified month ranged from 66-78% in the asoprisnil 10-mg group and 83-93% in the asoprisnil 25-mg group, significantly higher than with placebo (3-12%, P < 0.001). Hemoglobin increased rapidly (by month 2) with asoprisnil treatment and was significantly higher versus placebo throughout treatment. The primary fibroid and uterine volumes were significantly reduced from baseline through month 12 with asoprisnil 10 mg (median changes up to -48% and -28%, respectively) and 25 mg (median changes up to -63% and -39%, respectively) versus placebo (median changes up to +16% and +13%, respectively; all P < 0.001). Dose-dependent, significant improvements in HRQL (Uterine Fibroid Symptom and Quality of Life instrument) were observed with asoprisnil treatment. Asoprisnil was generally well tolerated. Endometrial biopsies indicated dose- and time-dependent decreases in proliferative patterns and increases in quiescent or minimally stimulated endometrium at month 12 of treatment. Although not statistically significantly different at month 6, mean endometrial thickness at month 12 increased by ~2 mm in both asoprisnil groups compared with placebo (P < 0.01). This effect was associated with cystic changes in the endometrium on MRI and ultrasonography, which led to invasive diagnostic and therapeutic procedures in some asoprisnil-treated women. LIMITATIONS, REASONS FOR CAUTION: Most study participants were black; few Asian and Hispanic women participated. The study duration may have been insufficient to fully characterize the endometrial effects. WIDER IMPLICATIONS OF THE FINDINGS: Daily uninterrupted treatment with asoprisnil was highly effective in controlling menstrual bleeding, improving anemia, reducing fibroid and uterine volume, and increasing HRQL in women with HMB associated with uterine fibroids. However, this treatment led to an increase in endometrial thickness and invasive diagnostic and therapeutic procedures, with potential unknown consequences. STUDY FUNDING/COMPETING INTEREST(S): This trial was funded by AbbVie Inc. (prior sponsors: TAP Pharmaceutical Products Inc., Abbott Laboratories). E.A. Stewart was a site investigator in the Phase 2 study of asoprisnil and consulted for TAP during the design and conduct of these studies while at Harvard Medical School and Brigham and Women's Hospital. She received support from National Institutes of Health grants HD063312, HS023418 and HD074711 and research funding, paid to Mayo Clinic for patient care costs related to an NIH-funded trial from InSightec Ltd. She consulted for AbbVie, Allergan, Bayer HealthCare AG, Gynesonics, and Welltwigs. She received royalties from UpToDate and the Med Learning Group. M.P. Diamond received research funding for the conduct of the studies paid to the institution and consulted for AbbVie. He is a stockholder and board and director member of Advanced Reproductive Care. He has also received funding for study conduct paid to the institution from Bayer and ObsEva. A.R.W. Williams consulted for TAP and Repros Therapeutics Inc. He has current consultancies with PregLem SA, Gedeon Richter, HRA Pharma and Bayer. B.R. Carr consulted for and received research funding from AbbVie. E.R. Myers consulted for AbbVie, Allergan and Bayer. R.A. Feldman received compensation for serving as a principal investigator and participating in the conduct of the trial. W. Elger was co-inventor of several patents related to asoprisnil. C. Mattia-Goldberg is a former employee of AbbVie and may own AbbVie stock or stock options. B.M. Schwefel and K. Chwalisz are employees of AbbVie and may own AbbVie stock or stock options. TRIAL REGISTRATION NUMBER: NCT00152269, NCT00160381 (clinicaltrials.gov). TRIAL REGISTRATION DATE: 7 September 2005; 8 September 2005. DATE OF FIRST PATIENT'S ENROLMENT: 12 September 2002; 6 September 2002.

The B Cell Response to Foot-and-Mouth Disease Virus in Cattle following Sequential Vaccination with Multiple Serotypes.

Foot-and-mouth disease virus (FMDV) is a highly contagious viral disease. Antibodies are pivotal in providing protection against FMDV infection. Serological protection against one FMDV serotype does not confer interserotype protection. However, some historical data have shown that interserotype protection can be induced following sequential FMDV challenge with multiple FMDV serotypes. In this study, we have investigated the kinetics of the FMDV-specific antibody-secreting cell (ASC) response following homologous and heterologous inactivated FMDV vaccination regimes. We have demonstrated that the kinetics of the B cell response are similar for all four FMDV serotypes tested following a homologous FMDV vaccination regime. When a heterologous vaccination regime was used with the sequential inoculation of three different inactivated FMDV serotypes (O, A, and Asia1 serotypes) a B cell response to FMDV SAT1 and serotype C was induced. The studies also revealed that the local lymphoid tissue had detectable FMDV-specific ASCs in the absence of circulating FMDV-specific ASCs, indicating the presence of short-lived ASCs, a hallmark of a T-independent 2 (TI-2) antigenic response to inactivated FMDV capsid.IMPORTANCE We have demonstrated the development of intraserotype response following a sequential vaccination regime of four different FMDV serotypes. We have found indication of short-lived ASCs in the local lymphoid tissue, further evidence of a TI-2 response to FMDV.

TOWARDS A TREATMENT FOR DIABETIC RETINOPATHY: Intravitreal Toxicity and Preclinical Safety Evaluation of Inducible Nitric Oxide Synthase Inhibitors.

BACKGROUND: The purpose of this study is to determine the maximum tolerated dose of a single intravitreal injection of aminoguanidine and 1400W, 2 inhibitors of inducible nitric oxide synthase, in rabbit eyes. Inhibition of inducible nitric oxide synthase has already been shown to be beneficial in various animal models of diabetic eye disease. METHODS: Groups of 4 New Zealand white rabbits were injected with balanced salt solution in the right eye and a single dose of either aminoguanidine (5, 1, 0.25 mg) or 1400W (2 mg and 0.4 mg) in the left eye. Toxicity was assessed by slit-lamp and fundus examination, intraocular pressure and pachymetric measurements, and electrophysiologic and histologic analysis. RESULTS: Eyes injected with high doses of aminoguanidine (5 mg) or 1400W (2 mg) demonstrated severe retinal vascular attenuation and infarction. Lower doses of intravitreal aminoguanidine (1 mg) and 1400W (0.4 mg) caused no significant toxic ocular effects in rabbit eyes. CONCLUSION: If the difference in vitreal volume between rabbit eyes and human eyes is taken into account, aminoguanidine (2.7 mg) and 1400W (1 mg) would be reasonable intravitreal doses to test for safety and efficacy in early clinical trials.

Rapid consumer-based sensory characterization of requeijão cremoso, a spreadable processed cheese: Performance of new statistical approaches to evaluate check-all-that-apply data.

We investigated the performance of multidimensional alignment analysis and multidimensional scaling on phi coefficient values to evaluate check-all-that-apply questionnaire data. We evaluated 6 dairy foods belonging to the category of requeijão cremoso processed cheese (traditional, with starch, or with starch and vegetable fat). We obtained sensory descriptors using trained assessors in descriptive analysis for comparison. A check-all-that-apply questionnaire used with 121 consumers (77 women and 44 men; 18 to 57 yr old) proved to be a suitable alternative for sensory profiling, providing descriptions similar to descriptive analysis and discriminating between products. Multidimensional alignment analysis and multidimensional scaling were efficient and logical approaches for obtaining a deeper understanding of the data, allowing us to clarify the relationships between sensory descriptors and products and contribute to optimizing the different formulations of requeijão cremoso.

Reformulating Minas Frescal cheese using consumers' perceptions: Insights from intensity scales and check-all-that-apply questionnaires.

We evaluated the performance of check-all-that-apply (CATA) questions and intensity scales to describe Minas Frescal cheese and its reformulation based on consumers' perceptions. Ten commercial samples with different formulations (full-fat, low-fat, or low-lactose) were evaluated by 200 consumers divided equally into 2 groups: 1 evaluated samples and described their ideal cheese using intensity scales and 1 did the same using CATA questions. Both methodologies provided similar information about the sensory characteristics of the Minas Frescal cheeses, the description of the ideal product, and directions for product reformulation. The ideal Minas Frescal cheese was characterized by high moisture, intense white color, homogeneous mass, typical Minas Frescal cheese aroma and flavor, softness, and juiciness. For the intensity scales, the recommendation was to increase the typical aroma and flavor, salty taste, and juiciness, and to decrease the bitter flavor; for the CATA questions, only increasing the typical Minas Frescal cheese flavor was important for all classes of cheeses. Even for a heterogeneous product with no defined manufacturing protocol, both methodologies presented satisfactory results that should be considered for use by cheese producers and the dairy industry.

The B-cell response to foot-and-mouth-disease virus in cattle following vaccination and live-virus challenge.

Antibodies play a pivotal role against viral infection, and maintenance of protection is dependent on plasma and memory B-cells. Understanding antigen-specific B-cell responses in cattle is essential to inform future vaccine design. We have previously defined T-cell-dependent and -independent B-cell responses in cattle, as a prelude to investigating foot-and-mouth-disease-virus (FMDV)-specific B-cell responses. In this study, we have used an FMDV O-serotype vaccination (O1-Manisa or O SKR) and live-virus challenge (FMDV O SKR) to investigate the homologous and heterologous B-cell response in cattle following both vaccination and live-virus challenge. The FMDV O-serotype vaccines were able to induce a cross-reactive plasma-cell response, specific for both O1-Manisa and O SKR, post-vaccination. Post-FMDV O SKR live-virus challenge, the heterologous O1-Manisa vaccination provided cross-protection against O SKR challenge and cross-reactive O SKR-specific plasma cells were induced. However, vaccination and live-virus challenge were not able to induce a detectable FMDV O-serotype-specific memory B-cell response in any of the cattle. The aim of new FMDV vaccines should be to induce memory responses and increased duration of immunity in cattle.

Distinct immune responses and virus shedding in pigs following aerosol, intra-nasal and contact infection with pandemic swine influenza A virus, A(H1N1)09.

Influenza virus infection in pigs is a major farming problem, causing considerable economic loss and posing a zoonotic threat. In addition the pig is an excellent model for understanding immunity to influenza viruses as this is a natural host pathogen system. Experimentally, influenza virus is delivered to pigs intra-nasally, by intra-tracheal instillation or by aerosol, but there is little data comparing the outcome of different methods. We evaluated the shedding pattern, cytokine responses in nasal swabs and immune responses following delivery of low or high dose swine influenza pdmH1N1 virus to the respiratory tract of pigs intra-nasally or by aerosol and compared them to those induced in naturally infected contact pigs. Our data shows that natural infection by contact induces remarkably high innate and adaptive immune response, although the animals were exposed to a very low virus dose. In contacts, the kinetics of virus shedding were slow and prolonged and more similar to the low dose directly infected animals. In contrast the cytokine profile in nasal swabs, antibody and cellular immune responses of contacts more closely resemble immune responses in high dose directly inoculated animals. Consideration of these differences is important for studies of disease pathogenesis and assessment of vaccine protective efficacy.

Listening to music can influence hedonic and sensory perceptions of gelati.

The dominant taste sensations of three different types of chocolate gelati (milk chocolate, dark chocolate, and bittersweet chocolate) were determined using forty five trained panellists exposed to a silent reference condition and three music samples differing in hedonic ratings. The temporal dominance of sensations (TDS) method was used to measure temporal taste perceptions. The emotional states of panellists were measured after each gelati-music pairing using a scale specifically developed for this study. The TDS difference curves showed significant differences between gelati samples and music conditions (p < 0.05). Sweetness was perceived more dominant when neutral and liked music were played, while bitterness was more dominant for disliked music. A joint Canonical Variate Analysis (CVA) further explained the variability in sensory and emotion data. The first and second dimensions explained 78% of the variance, with the first dimension separating liked and disliked music and the second dimension separating liked music and silence. Gelati samples consumed while listening to liked and neutral music had positive scores, and were separated from those consumed under the disliked music condition along the first dimension. Liked music and disliked music were further correlated with positive and negative emotions respectively. Findings indicate that listening to music influenced the hedonic and sensory impressions of the gelati.

Picky eating: Associations with child eating characteristics and food intake.

Food rejection behaviors such as picky eating are of concern for many parents and attempts to increase healthy food intake can cause distress at mealtimes. An important limitation in most of the picky eating studies is that they cover few characteristics of picky eating behaviors and use limited measures of food intake. The objective of this study was to explore the associations between picky eating, child eating characteristics, and food intake among toddlers 12-47.9 months old (n = 2371) using data from the 2008 Feeding Infants and Toddlers Study (FITS). Logistic regression was used to examine associations between demographic and feeding characteristics and picky eater status. Differences in food group intake between picky and non-picky eaters were analyzed. Picky eaters were more likely to be neophobic, texture resistant, and to eat only favorite foods, In addition, the parents of picky eaters tend to offer new food a greater number of times than those of non-picky eaters before deciding that the child does not like it. Picky eaters showed significant lower intakes of eggs, burritos/tacos/enchiladas/nachos and sandwiches than non-picky eaters. Picky eaters consumed fewer vegetables from the "other vegetables" category and less raw vegetables than non-picky eaters. Neophobia, eating only favorite foods and difficulties with texture are all important characteristics of picky eaters which need to be integrated in studies measuring picky eating behaviors. Food intake of picky eaters differs only slightly from non-picky eaters. Because picky eating is a major parental concern, feeding strategies and advice related to the relevant characteristics of picky eating behavior need to be developed and assessed for their effectiveness.

Comparison of the management and in-hospital outcomes of acute coronary syndrome patients in Australia and New Zealand: results from the binational SNAPSHOT acute coronary syndrome 2012 audit.

BACKGROUND/AIMS: We aimed to assess differences in patient management, and outcomes, of Australian and New Zealand patients admitted with a suspected or confirmed acute coronary syndrome (ACS). METHODS: We used comprehensive data from the binational Australia and New Zealand ACS 'SNAPSHOT' audit, acquired on individual patients admitted between 00.00 h on 14 May 2012 to 24.00 h on 27 May 2012. RESULTS: There were 4387 patient admissions, 3381 (77%) in Australia and 1006 (23%) in New Zealand; Australian patients were slightly younger (67 vs 69 years, P = 0.0044). Of the 2356 patients with confirmed ACS, Australian patients were at a lower cardiovascular risk with a lower median Global Registry Acute Coronary Events score (147 vs 154 P = 0.0008), but as likely to receive an invasive coronary angiogram (58% vs 54%, P = 0.082), or revascularisation with percutaneous coronary intervention (32% vs 31%, P = 0.92) or coronary artery bypass graft surgery (7.0% vs 5.6%, P = 0.32). Of the 1937 non-segment elevation myocardial infarction/unstable angina pectoris (NSTEMI/UAP) patients, Australian patients had a shorter time to angiography (46 h vs 67 h, P < 0.0001). However, at discharge, Australian NSTEMI/UAP survivors were less likely to receive aspirin (84% vs 89%, P = 0.0079, a second anti-platelet agent (57% vs 63%, P = 0.050) or a beta blocker (67% vs 77%, P = 0.0002). In-hospital death rates were not different (2.7% vs 3.2%, P = 0.55) between Australia and New Zealand. CONCLUSIONS: Overall more similarities were seen, than differences, in the management of suspected or confirmed ACS patients between Australia and New Zealand. However, in several management areas, both countries could improve the service delivery to this high-risk patient group.

Improved adjuvanting of seasonal influenza vaccines: preclinical studies of MVA-NP+M1 coadministration with inactivated influenza vaccine.

Licensed seasonal influenza vaccines induce antibody (Ab) responses against influenza hemagglutinin (HA) that are limited in their ability to protect against different strains of influenza. Cytotoxic T lymphocytes recognizing the conserved internal nucleoprotein (NP) and matrix protein (M1) are capable of mediating a cross-subtype immune response against influenza. Modified vaccinia Ankara (MVA) virus encoding NP and M1 (MVA-NP+M1) is designed to boost preexisting T-cell responses in adults in order to elicit a cross-protective immune response. We examined the coadministration of HA protein formulations and candidate MVA-NP+M1 influenza vaccines in murine, avian, and swine models. Ab responses postimmunization were measured by ELISA and pseudotype neutralization assays. Here, we demonstrate that MVA-NP+M1 can act as an adjuvant enhancing Ab responses to HA while simultaneously inducing potent T-cell responses to conserved internal Ags. We show that this regimen leads to the induction of cytophilic Ab isotypes that are capable of inhibiting hemagglutination and in the context of H5 exhibit cross-clade neutralization. The simultaneous induction of T cells and Ab responses has the potential to improve seasonal vaccine performance and could be employed in pandemic situations.

Measuring scattering distributions in scanning helium microscopy.

A scanning helium microscope typically utilises a thermal energy helium atom beam, with an energy and wavelength (¡100meV, ∼0.05 nm) particularly sensitive to surface structure. An angular detector stage for a scanning helium microscope is presented that facilitates the in-situ measurement of scattering distributions from a sample. We begin by demonstrating typical elastic and inelastic scattering from ordered surfaces. We then go on to show the role of topography in diffuse scattering from disordered surfaces, observing deviations from simple cosine scattering. In total, these studies demonstrate the wealth of information that is encoded into the scattering distributions obtained with the technique.

CD4+ T-cell responses to foot-and-mouth disease virus in vaccinated cattle.

We have performed a series of studies to investigate the role of CD4(+) T-cells in the immune response to foot-and-mouth disease virus (FMDV) post-vaccination. Virus neutralizing antibody titres (VNT) in cattle vaccinated with killed FMD commercial vaccine were significantly reduced and class switching delayed as a consequence of rigorous in vivo CD4(+) T-cell depletion. Further studies were performed to examine whether the magnitude of T-cell proliferative responses correlated with the antibody responses. FMD vaccination was found to induce T-cell proliferative responses, with CD4(+) T-cells responding specifically to the FMDV antigen. In addition, gamma interferon (IFN-γ) was detected in the supernatant of FMDV antigen-stimulated PBMC and purified CD4(+) T-cells from vaccinated cattle. Similarly, intracellular IFN-γ could be detected specifically in purified CD4(+) T-cells after restimulation. It was not possible to correlate in vitro proliferative responses or IFN-γ production of PBMC with VNT, probably as a consequence of the induction of T-independent and T-dependent antibody responses and antigen non-specific T-cell responses. However, our studies demonstrate the importance of stimulating CD4(+) T-cell responses for the induction of optimum antibody responses to FMD-killed vaccines.

Effect of insurance status on patients admitted for acute diverticulitis.

AIM: The study aimed to evaluate the relationship between insurance status and the management and outcome of acute diverticulitis in a nationally representative sample. METHOD: A retrospective cohort analysis of a nationally representative sample of 1 031 665 hospital discharges of patients admitted for acute diverticulitis in the 2006-2009 Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project data set. The main outcome measures included state at presentation (complicated/uncomplicated), management (medical/surgical), time to surgical intervention, type of operation and inpatient death. RESULTS: In total, 207 838 discharges were identified (including 37.0% with private insurance, 49.3% in Medicare, 5.6% in Medicaid and 5.8% uninsured) representing 1 031 665 total discharges nationally. Medicare patients were more likely to present with complicated diverticulitis compared with private insurance patients (23.8% vs 15.1%). Time to surgical intervention differed by insurance status. After adjusting for patient, hospital and treatment factors, Medicare patients were less likely than those with private insurance to undergo a procedure (Medicare OR = 0.86, 95% CI: 0.82-0.91), while the uninsured were more likely to undergo drainage (OR = 1.30, 95% CI: 1.16-1.46) or a colostomy only (OR = 1.70, 95% CI: 1.24-2.33). All patients without private insurance were more likely to die in hospital (Medicare OR = 1.29, 95% CI: 1.09-1.52; Medicaid OR = 1.55, 95% CI: 1.22-1.97; uninsured OR = 1.41, 95% CI: 1.07-1.87). CONCLUSION: In a nationally representative sample of patients with acute diverticulitis, patient management and outcome varied significantly by insurance status, despite adjustment for potential confounders. Providers might need to heighten surveillance for complications when treating patients without private insurance to improve outcome.

Immunization with matrix-, nucleoprotein and neuraminidase protects against H3N2 influenza challenge in pH1N1 pre-exposed pigs.

There is an urgent need for influenza vaccines providing broader protection that may decrease the need for annual immunization of the human population. We investigated the efficacy of heterologous prime boost immunization with chimpanzee adenovirus (ChAdOx2) and modified vaccinia Ankara (MVA) vectored vaccines, expressing conserved influenza virus nucleoprotein (NP), matrix protein 1 (M1) and neuraminidase (NA) in H1N1pdm09 pre-exposed pigs. We compared the efficacy of intra-nasal, aerosol and intra-muscular vaccine delivery against H3N2 influenza challenge. Aerosol prime boost immunization induced strong local lung T cell and antibody responses and abrogated viral shedding and lung pathology following H3N2 challenge. In contrast, intramuscular immunization induced powerful systemic responses and weak local lung responses but also abolished lung pathology and reduced viral shedding. These results provide valuable insights into the development of a broadly protective influenza vaccine in a highly relevant large animal model and will inform future vaccine and clinical trial design.

Assessment of T-dependent and T-independent immune responses in cattle using a B cell ELISPOT assay.

Understanding the mechanisms that maintain protective antibody levels after immunisation is important for vaccine design. In this study, we have determined the kinetics of plasma and memory B cells detectable in the blood of cattle immunised with model T-dependent or T-independent antigens. Immunisation with the T-D antigen resulted in an expansion of TNP-specific plasma cells post-TNP primary and booster immunisations, which was associated with increased titres of TNP-specific IgG antibodies. Although no TNP-specific memory B cells were detected in the T-D group following the primary immunisation, we detected an increase in the number of TNP-specific memory B cells post-TNP boost. In contrast, no TNP-specific plasma or memory B cells were detected after primary or secondary immunisation with the T-I antigen. We then investigated if immunisation with a third party antigen (tetanus toxin fragment C, TTC) would result in a bystander stimulation and increase the number of TNP-specific plasma and memory B cells in the T-D and/or T-I group. TTC immunisation in the T-D group resulted in a small increase in the number of TNP-specific plasma cells post-TTC primary immunisation and boost, and in an increase in the number of TNP-specific memory B cells post-TTC boost. This bystander effect was not observed in the animals previously immunised with the T-I antigen. In conclusion, the present study characterised for the first time the B cell response in cattle to immunisation with T-D and T-I antigens and showed that bystander stimulation of an established T-D B cell memory response may occur in cattle.

Overdose, opioid treatment admissions and prescription opioid pain reliever relationships: United States, 2010-2019.

Background: "As part of the U.S. government's urgent response to the epidemic of overdose deaths (1)" the United States Centers for Disease Control and Prevention (CDC) issued the "CDC Guideline for Prescribing Opioids for Chronic Pain-United States, 2016 (2)" (guideline) followed by the "CDC Clinical Practice Guideline for Prescribing Opioids-United States, 2022 (3) (guideline update). " The guideline and guideline update cite a direct correlation between prescription opioids sales (POS) and opioid treatment admissions (OTA) and prescription opioid deaths (POD), which was based on data from 1999 to 2010. This paper updates those relationships and includes the correlations between prescription opioid sales (POS) and any opioid deaths (AOD) and total overdose deaths (TOD) from 2010 to 2019. Methods: Linear regression models were fit to each response separately. Opioid sales (measured as MME (morphine milligram equivalent) per capita) was the independent variable. Total overdose deaths (TOD), any opioid overdose deaths (AOD), prescription opioid overdose deaths (POD) and opioid treatment admissions (OTA) were the dependent, response variables. The models were assessed using three criteria: the statistical significance of the model (Overall P-Value), the quality of the fit (R 2), and the sign of the slope coefficient (positive or negative). Results: The analyses revealed that the direct correlations (i.e., significant, positive slopes) reported by the CDC based on data from 1999 to 2010 no longer exist. Based on data from 2010 to 2019, the relationships either have reversed (i.e., significant, negative slopes) or are non-existent (i.e., no significant model). Conclusions: The guideline, guideline update, CDC's public, medical profession, and intergovernmental communications should be corrected/updated to state no direct correlation has existed between POS to OTA, POD, AOD, and TOD since 2010. Individualized patient care and public health policy should be amended accordingly.

Cattle remain immunocompetent during the acute phase of foot-and-mouth disease virus infection.

Infection of cattle with foot-and-mouth disease virus (FMDV) results in the development of long-term protective antibody responses. In contrast, inactivated antigen vaccines fail to induce long-term protective immunity. Differences between susceptible species have also been observed during infection with FMDV, with cattle often developing persistent infections whilst pigs develop more severe symptoms and excrete higher levels of virus. This study examined the early immune response to FMDV in naïve cattle after in-contact challenge. Cattle exposed to FMDV were found to be viraemic and produced neutralising antibody, consistent with previous reports. In contrast to previous studies in pigs these cattle did not develop leucopenia, and the proliferative responses of peripheral blood mononuclear cells to either mitogen or third party antigen were not suppressed. Low levels of type 1 interferon and IL-10 were detected in the circulation. Taken together, these results suggest that there was no generalised immunosuppression during the acute phase of FMDV infection in cattle.