Asthma and clinical outcomes of COVID-19 in a community setting.

OBJECTIVES: The association between asthma and COVID-19 mortality remains inconclusive. We examined the association between asthma and clinical outcomes of patients with COVID-19. STUDY DESIGN: A case-control study based on a surveillance cohort in Harris County, Texas. METHODS: Using the data of 21,765 patients who reported having at least one chronic health condition, we investigated the association between asthma and COVID-19 severity, characterized primarily by hospitalization and death. Unconditional logistic regression models were used to estimate the multivariable odds ratio (mOR) and its 95 % confidence interval (CI) of COVID-19 severity associated with asthma and other chronic lung diseases, adjusting for demographic and other comorbidities. A P-value < 0.005 was considered statistically significant after correcting multiple testing. RESULTS: In total, 3034 patients (13.9 %) had asthma, and 774 (3.56 %) had other chronic lung diseases. The case death rate among patients with asthma and other chronic lung diseases was 0.75 % and 19.0 %, respectively. Compared to patients without the respective conditions, patients with asthma had lower odds of death (mOR = 0.44, 95 % CI: 0.27-0.69), while patients with other chronic lung diseases had higher odds of hospitalization (mOR = 2.02, 95 % CI: 1.68-2.42) and death (mOR = 1.95, 95 % CI: 1.52-2.49) (P-values < 0.005). Risk factors for COVID-19 mortality included older age, male gender, diabetes, obesity, hypertension, cardiovascular disease, active cancer, and chronic kidney disease. CONCLUSIONS: The public health surveillance data suggested that preexisting asthma was inversely associated with COVID-19 mortality.

Sharing Ideas and Practice: Institutional Partnership Influences Change in Approaches to Teaching to Enhance Veterinary Education in Vietnam in Conjunction with an OIE Veterinary Education Twinning Project.

A World Organisation for Animal Health (OIE) Veterinary Education Twinning Project was established between the veterinary schools at Nong Lam University (NLU) in Ho Chi Minh City, Vietnam, and the University of Queensland, Gatton, Australia, as part of the scheme established to promote high-quality veterinary services through improved veterinary education. Included in the partnership's primary aims were building the capacity of veterinary teaching staff with respect to general teaching practice and also in response to identified deficiency areas, and to develop outcome assessment processes. One challenge facing the project was the different approaches and experiences of teaching and learning for the faculty and students between the two widely different historical and cultural contexts of Australia and Vietnam. The project enhanced the pedagogy capability in NLU faculty and introduced student-focused approaches to teaching. The NLU staff involved in the project strongly embraced a student-centered approach to learning and case-based teaching in particular, adopting these strategies in their own teaching. An analysis of students' approach to learning demonstrates that the majority preferred a deep approach to learning and that these students valued case studies, problem-solving exercises, and working in small groups during teaching sessions more than students who took a surface approach to learning. An improved recognition of the ways the Vietnamese students approach their learning in their home country will guide future teaching design, as well as give insight into the approaches to teaching for Southeast Asian students within the Australian veterinary science programs.

Community-led HIV testing services including HIV self-testing and assisted partner notification services in Vietnam: lessons from a pilot study in a concentrated epidemic setting.

INTRODUCTION: The HIV epidemic in Vietnam is concentrated in key populations and their partners - people who inject drugs, men who have sex with men, sex workers and partners of people living with HIV. These groups have poor access to and uptake of conventional HIV testing services (HTS). To address this gap, lay provider- and self-testing and assisted partner notification (aPN) were introduced and delivered by the community. We explored the feasibility and effectiveness of implementing aPN as part of community testing services for key populations. METHODS: Lay provider testing and self-testing was started in January 2017, and targeted key populations and their partners. Since July 2017, aPN was introduced. HTS was offered at drop-in houses or coffee shops in Thai Nguyen and Can Tho provinces. All self-testing was assisted and observed by peer educators. Both in-person and social network methods were used to mobilize key populations to test for HIV and offer HTS to partners of people living with HIV. Client-level data, including demographic information and self-reported risk behaviour, were collected on site by peer educators. RESULTS: Between January 2017 and May 2018, 3978 persons from key populations were tested through community-led HTS; 66.7% were first-time testers. Of the 3978 clients, 3086 received HTS from a lay provider and 892 self-tested in the presence of a lay provider. Overall, 245 (6.2% of tested clients) had reactive results, 231 (94.3%) were confirmed to be HIV positive; 215/231 (93.1%) initiated antiretroviral therapy (ART). Of 231 adult HIV-positive clients, 186 (80.5%) were provided voluntary aPN, and 105 of their partners were contacted and received HTS. The ratio of partners who tested for HIV per index client was 0.56. Forty-four (41.9%) partners of index clients receiving HTS were diagnosed with HIV, 97.7% initiated ART during the study period. No social harm was identified or reported. CONCLUSIONS: Including aPN as part of community-led HTS for key populations and their partners is feasible and effective, particularly for reaching first-time testers and undiagnosed HIV clients. Scale-up of aPN within community-led HTS for key populations is essential for achieving the United Nations 90-90-90 targets in Vietnam.

Utility of routine oral contrast study for detecting postesophagectomy anastomotic leak - a systematic review and meta-analysis.

Oral contrast studies are used to detect anastomotic leak (AL) postesophagectomy. However, recent evidence suggests oral contrast studies have low sensitivity in detecting ALs, and their false positive results can lead to unnecessary prolonged hospital stay. The objective of this study was to determine if oral contrast studies should be used routinely post-esophagectomy for cancer. A systematic literature search was conducted for studies published between January 1990 and June 2018. Data extracted for analyses included type of esophagectomy, operative morbidity (such as AL and pneumonia), mortality rates, timing of contrast study, and type of oral contrast used. The sensitivity, specificity, and positive and negative predictive values of routine oral contrast studies to detect AL were calculated using the aforementioned variables. Two hundred and forty-seven studies were reviewed with 16 studies included in the meta-analysis. Postoperative oral contrast study was performed in 94.0% of cases between day 5 and 7. The rates of early and delayed leaks were 2.4% (1.8%-3.3%) and 2.8% (1.8%-4.4%), respectively. Routine contrast studies have a sensitivity and specificity of 0.44 (0.32-0.57) and 0.98 (0.95-0.99), respectively. Analysis of covariates revealed that sensitivity is reduced in centers with a higher volume of cases (greater than 15 per year: 0.50 [0.34-0.75; p = 0.0008]) and specificity was higher in centers with a lower leak rate. Given its poor sensitivity and inability to detect early/delayed AL, oral contrast study should be used selectively with endoscopy and/or computerized tomography scan to assess surgical anastomoses following esophagectomy.

Screening and management of the small for gestational age fetus in the UK: A survey of practice.

BACKGROUND: Antenatal detection of the small for gestational (SGA) fetus has become an important indicator of quality of antenatal care in the UK. This has been driven by a desire to reduce stillbirth in this at risk group. METHODS: We conducted a postal survey of 187 NHS consultant units within the UK to determine what the current practice for the detection and subsequent management of the suspected SGA fetus was following the guidance from the Royal College of Obstetricians and Gynaecologists (RCOG) in 2013. RESULTS: The survey was performed in 3 rounds between 2016 and 2017 with a response rate of 65%. 85% of units assessed risk factors for SGA at booking. 81% of units used a customized symphysis fundal height (SFH) chart to screen for SGA with 95% of them using a cut off of <10th centile to refer for ultrasound assessment. When ultrasound is used to detect SGA, 80% of units used estimated fetal weight (EFW), with 89% of these using a cut off of <10th centile to diagnose SGA. Umbilical artery (UA) Doppler monitoring was undertaken in 97% of management and 94% delivered after 37 weeks. Only 24% of units had a dedicated fetal growth clinic, whilst 48% of units were able to offer computerised CTG to monitor the SGA fetus. CONCLUSIONS: Overall there is consistency in the screening methods for SGA (customised SFH charts) and identification of suspected SGA (SFH <10th centile, EFW <10th centile, UA monitoring and induction of labour at term). There was a low uptake of computerized CTG to monitor SGA babies and a low number of specialised fetal growth clinics.

The Gopen-Yang Superior Semicircular Canal Dehiscence Questionnaire: development and validation of a clinical questionnaire to assess subjective symptoms in patients undergoing surgical repair of superior semicircular canal dehiscence.

OBJECTIVE: To characterise subjective symptoms in patients undergoing surgical repair of superior semicircular canal dehiscence. METHODS: Questionnaires assessing symptom severity and impact on function and quality of life were administered to patients before superior semicircular canal dehiscence surgery, between June 2011 and March 2016. Questionnaire sections included general quality of life, internal amplified sounds, dizziness and tinnitus, with scores of 0-100 points. RESULTS: Twenty-three patients completed the questionnaire before surgery. Section scores (mean±standard deviation) were: 38.2 ± 25.2 for general quality of life, 52.5 ± 23.9 for internal amplified sounds, 35.1 ± 28.8 for dizziness, 33.3 ± 30.7 for tinnitus, and 39.8 ± 22.2 for the composite score. Cronbach's α statistic averaged 0.93 (range, 0.84-0.97) across section scores, and 0.83 for the composite score. CONCLUSION: The Gopen-Yang Superior Semicircular Canal Dehiscence Questionnaire provides a holistic, patient-centred characterisation of superior semicircular canal dehiscence symptoms. Internal consistency analysis validated the questionnaire and provided a quantitative framework for further optimisation in the clinical setting.

Predictors of responses to immune checkpoint blockade in advanced melanoma.

Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.

Reduced turn-around time for Mycobacterium tuberculosis drug susceptibility testing with a proportional agar microplate assay.

Multidrug-resistant tuberculosis is a major issue worldwide; however, accessibility to drug susceptibility testing (DST) is still limited in developing countries, owing to high costs and complexity. We developed a proportion method on 12-well microplates for DST. The assay reduced the time to results to <12 days and <10 days when bacterial growth was checked with the naked eye or a microscope, respectively. Comparison with the Canetti-Grosset method showed that the results of the two assays almost overlapped (kappa index 0.98 (95% CI 0.91-1.00) for isoniazid, rifampicin, streptomycin; and kappa index 0.92 (95% CI 0.85-0.99) for ethambutol). The sequencing of genes involved in drug resistance showed similar level of phenotype-genotype agreement between techniques. Finally, measurement of the MICs of rifampicin and ethambutol suggests that the currently used critical ethambutol concentration should be revised, and that the current molecular drug susceptibility tests for rifampicin need to be re-evaluated, as in vitro rifampicin-sensitive isolates could harbour drug resistance-associated mutation(s).

Meniscus treatment and age associated with narrower radiographic joint space width 2-3 years after ACL reconstruction: data from the MOON onsite cohort.

OBJECTIVE: To identify risk factors for radiographic signs of post-traumatic osteoarthritis (OA) 2-3 years after anterior cruciate ligament (ACL) reconstruction through multivariable analysis of minimum joint space width (mJSW) differences in a specially designed nested cohort. METHODS: A nested cohort within the Multicenter Orthopaedic Outcomes Network (MOON) cohort included 262 patients (148 females, average age 20) injured in sport who underwent ACL reconstruction in a previously uninjured knee, were 35 or younger, and did not have ACL revision or contralateral knee surgery. mJSW on semi-flexed radiographs was measured in the medial compartment using a validated computerized method. A multivariable generalized linear model was constructed to assess mJSW difference between the ACL reconstructed and contralateral control knees while adjusting for potential confounding factors. RESULTS: Unexpectedly, we found the mean mJSW was 0.35 mm wider in ACL reconstructed than in control knees (5.06 mm (95% CI 4.96-5.15 mm) vs 4.71 mm (95% CI 4.62-4.80 mm), P < 0.001). However, ACL reconstructed knees with meniscectomy had narrower mJSW compared to contralateral normal knees by 0.64 mm (95% C.I. 0.38-0.90 mm) (P < 0.001). Age (P < 0.001) and meniscus repair (P = 0.001) were also significantly associated with mJSW difference. CONCLUSION: Semi-flexed radiographs can detect differences in mJSW between ACL reconstructed and contralateral normal knees 2-3 years following ACL reconstruction, and the unexpected wider mJSW in ACL reconstructed knees may represent the earliest manifestation of post-traumatic osteoarthritis and warrants further study.

Identification of Sc-type ILV6 as a target to reduce diacetyl formation in lager brewers' yeast.

Diacetyl causes an unwanted buttery off-flavor in lager beer. It is spontaneously generated from α-acetolactate, an intermediate of yeast's valine biosynthesis released during the main beer fermentation. Green lager beer has to undergo a maturation process lasting two to three weeks in order to reduce the diacetyl level below its taste-threshold. Therefore, a reduction of yeast's α-acetolactate/diacetyl formation without negatively affecting other brewing relevant traits has been a long-term demand of brewing industry. Previous attempts to reduce diacetyl production by either traditional approaches or rational genetic engineering had different shortcomings. Here, three lager yeast strains with marked differences in diacetyl production were studied with regard to gene copy numbers as well as mRNA abundances under conditions relevant to industrial brewing. Evaluation of data for the genes directly involved in the valine biosynthetic pathway revealed a low expression level of Sc-ILV6 as a potential molecular determinant for low diacetyl formation. This hypothesis was verified by disrupting the two copies of Sc-ILV6 in a commercially used lager brewers' yeast strain, which resulted in 65% reduction of diacetyl concentration in green beer. The Sc-ILV6 deletions did not have any perceptible impact on beer taste. To our knowledge, this has been the first study exploiting natural diversity of lager brewers' yeast strains for strain optimization.

Biodegradation of estrogen conjugates by bacteria isolated from river sediments.

The objective of this study was to investigate the ability of E. coli in river sediments to degrade estrogen conjugates. Biodegradation experiments on glucuronide estrogens (E1-GLU, E2-GLU and E3-GLU) using E. coli, non-E. coli bacteria as well as sediment crude extracts were carried out in batch mode. A pure identified E. coli strain (KCTC 2571) was used for comparison of enzyme activity. The results showed that the degradation rate of estrogen conjugates by KCTC 2571 and E. coli isolated from sediments followed a similar trend. Fecal bacteria showed a high ability to deconjugate glucuronided estrogens. Approximately 50% of glucuronide moieties were cleaved within 4 h of contact time in experiments using pure E. coli. The degradation rate was slower in experiments using crude extracts of sediments, and conjugated estrogens were not completely degraded even after 12 h of reaction. These results provide a clear understanding of the fate and behavior of estrogen by bacteria in the environment.

Tribological property of the cobalt-chromium femoral head with different regions of wear in total hip arthroplasty.

The tribological properties of engineering and biological materials have been investigated at microscale levels through the calculation of the surface roughness and frictional coefficient using atomic force microscopy (AFM). Although a number of previous studies have reported the frictional coefficients of diverse bearing materials in total hip arthroplasty (THA), the relationship between the surface roughness and frictional coefficient of bearing materials of THA have not been reported, and furthermore, the tribological properties for different wear regions of a cobalt-chromium (Co-Cr) femoral head have not been well identified. Therefore, the objective of this study is to investigate the relationships between the surface roughness, frictional coefficient, and hardness for both the main-wear and the least-wear regions of a Co-Cr femoral head 10 years after THA. The average Vickers hardness of the Co-Cr femoral head was 380.7 +/- 11.3 HV. With the scanned area of 25 microm x 25 microm through AFM, the frictional coefficients of the main-wear and the least-wear regions were 0.229 +/- 0.054 and 0.243 +/- 0.059, respectively, and showed no statistical differences between these two regions (p = 0.449). However, differences in the surface roughness (Rq) between the main-wear region (Rq = 96.5 +/- 26.2 nm) and the least-wear region (Rq = 17.7 +/- 4.2 nm) were statistically significant (p < 0.0001). The results of the current study suggest that the frictional property of the Co-Cr femoral head is not significantly correlated with its surface roughness, and also provide guidelines for improving the surface characteristics of metallic implant materials.

Genetic improvement of brewer's yeast: current state, perspectives and limits.

Brewer's yeast strain optimisation may lead to a more efficient beer production process, better final quality or healthier beer. However, brewer's yeast genetic improvement is very challenging, especially true when it comes to lager brewer's yeast (Saccharomyces pastorianus) which contributes to 90% of the total beer market. This yeast is a genetic hybrid and allopolyploid. While early studies applying traditional genetic approaches encountered many problems, the development of rational metabolic engineering strategies successfully introduced many desired properties into brewer's yeast. Recently, the first genome sequence of a lager brewer's strain became available. This has opened the door for applying advanced omics technologies and facilitating inverse metabolic engineering strategies. The latter approach takes advantage of natural diversity and aims at identifying and transferring the crucial genetic information for an interesting phenotype. In this way, strains can be optimised by introducing "natural" mutations. However, even when it comes to self-cloned strains, severe concerns about genetically modified organisms used in the food and beverage industry are still a major hurdle for any commercialisation. Therefore, research efforts will aim at developing new sophisticated screening methods for the isolation of natural mutants with the desired properties which are based on the knowledge of genotype-phenotype linkage.

Individual QTLs controlling quantitative variation in blood pressure inherited in a Mendelian mode.

We studied three possible genotypes at 10 well-defined blood pressure (BP) QTLs using congenic rat lines. The central question was whether the hypertensive or normotensive allele is dominant, or whether there is partial dominance. The congenic strains were employed to investigate the BP effects of alleles originating from normotensive rats in the background of hypertensive Dahl salt-sensitive (DSS) rats. The normotensive alleles at eight QTLs were fully dominant over DSS alleles, which we tentatively interpreted as indicating that DSS rats incurred a loss of function at these loci and that the QTLs produced BP-reducing agents. In contrast, the normotensive allele of only one QTL was recessive over its DSS counterpart, implying a gain of function at this QTL or a null allele involved in generating a BP-elevating agent. Only one locus, C17QTL, had alleles exhibiting partial dominance. These estimates of dominance differ considerably from those obtained by QTL analysis in a F2 cross. This disagreement demonstrates the importance of establishing a cause-effect relationship between a QTL and its phenotypic effect via congenic strains. The dominance relationships suggest pertinent strategies for gene identification and pharmaceutical intervention.

Factors influencing the diagnosis and treatment of periodontal disease by dental practitioners in Victoria.

BACKGROUND: Healthy periodontal tissues are essential to overall dental health. Therefore, the detection and management of periodontal disease is an integral part of general dental practice. The aim of this study was to investigate confidence in diagnosis and management of periodontal disease by general dental practitioners (GDPs), assess if the Dental Practice Board guidelines on periodontal record keeping are being addressed, and, if necessary, try to find ways of improving the periodontal knowledge of GDPs. METHODS: A survey assessing practitioner confidence in diagnosing and treating periodontal disease was sent to a random selection of 550 dental care providers registered with the Dental Practice Board of Victoria. RESULTS: Two hundred and eighty five (51.8 per cent) of questionnaires were returned completed. It was found that 79.7 per cent of the sampled population screened all new patients for periodontal disease. The majority of respondents felt confident to diagnose and treat gingivitis and initial periodontitis. However, only 61.9 per cent felt confident to diagnose aggressive/early onset periodontitis, and many were not confident in treating advanced periodontitis (36.3 per cent) or aggressive periodontitis (51.6 per cent). The majority of dentists reported that they provided most of the non surgical periodontal therapy to their patients, while most surgical treatments were referred to specialist periodontists. Factors deemed to be important in influencing the decision to provide periodontal treatment included level of training and ability to motivate patients to improve oral hygiene. Many responents requested periodontic continuing education (CE) courses be run. CONCLUSIONS: Most of the dentists surveyed were confident to diagnose periodontal disease and to treat the more common presentations of periodontal disease. There is some evidence to suggest that some practitioners are not following the minimum requirements set by the Dental Practice Board of Victoria in relation to periodontal record keeping. The results also indicate a need for more periodontic CE courses in Victoria.

Methylene blue for the treatment and prophylaxis of ifosfamide-induced encephalopathy.

Ifosfamide (IFOS) is used in cancer treatment. Ifosfamide-induced encephalopathy (IIE) can result in treatment delay or discontinuation as well as morbidity and mortality. Cases using methylene blue (MB) in acute and prophylactic treatments are discussed. For acute use, marked central nervous system (CNS) improvement occurred within 24h of MB administration. For prophylactic use, the severity of the symptoms decreased significantly compared with previous treatment cycles, and enabled patients to continue further IFOS therapy. MB has potential use in both the acute treatment and prophylaxis of IIE.

Adipophilin is a sensitive marker for lipid loading in human blood monocytes.

Adipophilin, a marker of lipid accumulation initially described in adipocytes, was recently shown to be induced in macrophage foam cells. We found that even freshly isolated blood monocytes express adipophilin and that the amount of adipophilin protein is variable in monocytes from different healthy individuals. However, the physiological expression of adipophilin does not correlate with the levels of free fatty acids, cholesterylesters or free cholesterol. Enzymatically modified low-density lipoprotein (E-LDL) induces rapid foam cell formation in monocytes and upregulates adipophilin mRNA and protein within 2 h of incubation. This rapid induction of adipophilin is accompanied by a significant increase of free fatty acids in monocytes incubated with E-LDL. Adipophilin facilitates the uptake of free fatty acids, and here we demonstrate that free fatty acids increase is related to the early upregulation of adipophilin expression in blood monocytes. Fatty acids are ligands for peroxisome proliferator-activated receptor-gamma (PPARgamma), and the upregulation of adipophilin mRNA by PPARgamma agonists like 15d-PGJ(2) and ciglitazone indicates that PPARgamma may mediate the induction of adipophilin expression in human blood monocytes.

Enzymatically degraded LDL preferentially binds to CD14(high) CD16(+) monocytes and induces foam cell formation mediated only in part by the class B scavenger-receptor CD36.

Heterogeneity of peripheral blood monocytes is characterized by specific patterns in the membrane expression of Fc gamma-receptor III (FcgammaRIII/CD16) and the lipopolysaccharide receptor (LPS receptor CD14), allowing discrimination of distinct subpopulations. The aim was to analyze the correlation of these phenotypic differences to the early interaction of freshly isolated monocytes with modified lipoproteins by the use of either enzymatically degraded low density lipoprotein (E-LDL), acetylated low density lipoprotein (ac-LDL), oxidized low density lipoprotein (ox-LDL), or native low density lipoprotein. Highest E-LDL binding was observed on CD14(high) CD16(+) monocytes as determined by flow cytometry, suggesting a selective interaction of E-LDL with distinct subpopulations of monocytes. E-LDL induced rapid foam cell formation both in predifferentiated monocyte-derived macrophages and, in contrast to ac-LDL or ox-LDL, also in freshly isolated peripheral blood monocytes. This was accompanied by upregulation of the 2 class B scavenger receptors CLA-1/SR-BI (CD36 and LIMPII Analogous-1/scavenger receptor type B class I) and CD36. Cellular binding and uptake of E-LDL was neither competed by ac-LDL nor the class A scavenger-receptor inhibitor polyinosinic acid but was partially inhibited by an excess of ox-LDL. In predifferentiated monocyte-derived macrophages, an anti-CD36 antibody inhibited cellular binding and uptake of E-LDL by approximately 20%, suggesting that recognition of these hydrolase-modified low density lipoprotein particles is mediated only in part by the class B scavenger receptor CD36.

Review of aortoiliac aneurysms with spontaneous large vein fistula.

BACKGROUND: Arteriovenous fistula is a rare complication of aortoiliac aneurysmal disease, accounting for less than 2% of clinical presentations. METHODS: In addition to the 191 cases reviewed in the literature, an additional 14 cases seen at Royal Melbourne Hospital over the last 22 years are presented to illustrate the challenges in the diagnosis of this condition. CONCLUSION: An increase in awareness may lead to better management of these patients.