The acceptability and usability of two HIV self-test kits among men who have sex with men: a randomised crossover trial.

OBJECTIVES: To compare the usability and acceptability of oral fluid- and blood-based HIV self-test kits among men who have sex with men in Australia. DESIGN: Randomised crossover trial. SETTING, PARTICIPANTS: Gay, bisexual, and other men aged 18 years or older who have sex with men, who attended two metropolitan sexual health clinics in Sydney and Melbourne, 7 January - 10 December 2019. MAIN OUTCOME MEASURES: Ease of use of HIV self-test kits; preferred HIV self-test type; difficulties encountered during HIV self-testing. RESULTS: 170 men were recruited (median age, 34 years; interquartile range, 29-43 years); 144 identified as gay (85%), 96 were born outside Australia (57%). Participants were more likely to report the oral fluid HIV self-test was easy to use than the blood-based self-test (oral fluid, 99%; blood, 86%; odds ratio [OR], 3.0; 95% confidence interval [CI], 1.4-6.6). The oral fluid test was preferred by 98 participants (58%; 95% CI, 50-65%), the blood-based test by 69 (41%; 95% CI, 33-48%). Difficulties with the oral fluid test kit identified by observing nurses included problems placing the buffer solution into the stand (40 of 170 participants, 24%) and not swabbing both gums (23 of 169, 14%); difficulties with the blood-based test kit included problems filling the device test channel (69 of 170, 41%) and squeezing the finger firmly enough to generate a blood drop (42 of 170, 25%). No participant received an invalid result with the oral fluid self-test; two of 162 participants (1%) received invalid results with the blood self-test. After adjusting for age, education level, and ethnic background, characteristics associated with higher odds of using HIV self-testing in the future were overseas birth (adjusted OR, 3.07; 95% CI, 1.42-6.64), and self-evaluated ease of use and confidence in using the kits. CONCLUSION: It is important to provide options for obtaining both oral fluid- and blood-based HIV self-tests. The usability and acceptability of both kits were high, but the ease of use and perceived accuracy influenced test kit preference.

EUS-guided confocal laser endomicroscopy: prediction of dysplasia in intraductal papillary mucinous neoplasms (with video).

BACKGROUND AND AIMS: Previous studies have validated EUS-guided needle-based confocal laser endomicroscopy (nCLE) diagnosis of intraductal papillary mucinous neoplasms (IPMNs). We sought to derive EUS-guided nCLE criteria for differentiating IPMNs with high-grade dysplasia/adenocarcinoma (HGD-Ca) from those with low/intermediate-grade dysplasia (LGD). METHODS: We performed a post hoc analysis of consecutive IPMNs with a definitive diagnosis from a prospective study evaluating EUS-guided nCLE in the diagnosis of pancreatic cysts. Three internal endosonographers reviewed all nCLE videos for the patients and identified potential discriminatory EUS-guided nCLE variables to differentiate HGD-Ca from LGD IPMNs (phase 1). Next, an interobserver agreement (IOA) analysis of variables from phase 1 was performed among 6 blinded external nCLE experts (phase 2). Last, 7 blinded nCLE-naïve observers underwent training and quantified variables with the highest IOA from phase 2 using dedicated software (phase 3). RESULTS: Among 26 IPMNs (HGD-Ca in 16), the reference standard was surgical histopathology in 24 and cytology confirmation of metastatic liver lesions in 2 patients. EUS-guided nCLE characteristics of increased papillary epithelial "width" and "darkness" were the most sensitive variables (90%; 95% confidence interval [CI], 84%-94% and 91%; 95% CI, 85%-95%, respectively) and accurate (85%; 95% CI, 78%-90% and 84%; 95% CI, 77%-89%, respectively) with substantial (κ = 0.61; 95% CI, 0.51-0.71) and moderate (κ = 0.55; 95% CI, 0.45-0.65) IOAs for detecting HGD-Ca, respectively (phase 2). Logistic regression models were fit for the outcome of HGD-Ca as predictor variables (phase 3). For papillary width (cut-off ≥50 µm), the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.95, respectively. For papillary darkness (cut-off ≤90 pixel intensity), the sensitivity, specificity, and AUC for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.90, respectively. CONCLUSIONS: In this derivation study, quantification of papillary epithelial width and darkness identified HGD-Ca in IPMNs with high accuracy. These quantifiable variables can be used in multicenter studies for risk stratification of IPMNs. (Clinical trial registration number: NCT02516488.).

Two novel adenoviruses found in Cave Myotis bats (Myotis velifer) in Oklahoma.

Bats are carriers of potentially zoonotic viruses, therefore it is crucial to identify viruses currently found in bats to better understand how they are maintained in bat populations and evaluate risks for transmission to other species. Adenoviruses have been previously detected in bats throughout the world, but sampling is still limited. In this study, 30 pooled-guano samples were collected from a cave roost of Myotis velifer in Oklahoma. A portion of the DNA polymerase gene from Adenoviridae was amplified successfully in 18 M. velifer samples; however, DNA sequence was obtained from only 6 of these M. velifer samples. One was collected in October 2016, one in March 2017, and 4 in July 2017. The October and March samples contained viral DNA that was 3.1% different from each other but 33% different than the novel viral sequence found in the July 2017 samples. Phylogenetic analysis of these fragments confirmed our isolates were from the genus Mastadenovirus and had genetic diversity ranging from 20 to 50% when compared to other bat adenoviruses.

High Frequency of Multiple Paternity in Eastern Red Bats, Lasiurus borealis, Based on Microsatellite Analysis.

Most species of bats give birth to only 1 pup each year, although Eastern red bats (Lasiurus borealis) can produce up to 5 pups per litter. Offspring in a single litter have been documented to be at different stages of development, suggesting that multiple paternity occurs. We tested the null hypothesis of genetic monogamy in red bats using 6 autosomal microsatellites and 1 X-linked microsatellite from 31 parent/offspring groups for a total of 128 bats. We sampled both pregnant females and mothers with pups that were obtained from bats submitted to departments of health in Oklahoma and Texas for rabies testing. Multiple paternity was assessed using a maximum-likelihood approach, hypothesis testing, and X-linked locus exclusion. The mean polymorphic information content of our markers was high (0.8819) and combined non-exclusion probability was low (0.00027). Results from the maximum-likelihood approach showed that 22 out of 31 (71%) parent/offspring groups consisted of half siblings, hypothesis testing rejected full sibship in 61% of parent/offspring groups, and X-linked locus exclusion suggested multiple paternity in at least 12 parent/offspring groups, rejecting our hypothesis of genetic monogamy. This frequency of multiple paternity is the highest reported thus far for any bat species. High levels of multiple paternity have the potential to impact interpretations of genetic estimates of effective population size in this species. Further, multiple paternity might be an adaptive strategy to allow for increased genetic variation and large litter size, which would be beneficial to a species threatened by population declines from wind turbines.

Effect of mono- and diglycerides on the digestion and absorption of lutein in lymph fistula rats.

Breast milk lutein is better absorbed by infants than lutein delivered in infant formula. Therefore, we wanted to better understand the possible absorption differences of lutein in breast milk vs. that in infant formula by determining its bioavailability after gastric administration and whether the intestinal absorption of lutein can be improved by using new delivery vehicles. Study 1 compared the intestinal uptake,and the lymphatic and portal transport of lutein in conscious lymph fistula rats. Four groups of lymph- and portal vein-cannulated rats ( n = 8-10/group) were randomized to receive via gastric tube increasing doses (10, 20, 40, or 80 mg/kg) of 20% lutein in safflower oil (SO) suspension to assess whether there was a saturable level of lutein that could be absorbed and transported in lymph. Aliquots of hourly portal blood and lymph were taken for lutein and zeaxanthin analyses. The dose-response study showed that 20 mg/kg lutein was the saturable level of lymphatic lutein absorption with no lutein detected in portal circulation at any dosage level tested. Study 2 randomized five groups of lymph fistula rats ( n = 4-9/group) to receive 20 mg/kg lutein from either lutein in SO or lutein in four different mono- and diglyceride oils (MDGs). Gastric infusion of lutein suspended in MDG (20 mg/kg) significantly improved (71-211%, P < 0.05) lymphatic lutein output 2-6 h after lipid feeding vs. lutein in SO. Lymphatic zeaxanthin (10% of the lutein fed mixture) transport in both Study 1 and Study 2 followed that of lutein. We conclude that a mixture of MDGs helps solubilize lutein and facilitate gastrointestinal micelle formation, thus improving lymphatic lutein absorption compared with triglyceride oils. NEW & NOTEWORTHY This paper describes how lutein is digested and absorbed by the gastrointestinal tract by using the conscious lymph fistula rat model. Our dose-response study showed that absorption and lymphatic transport of lutein is a saturable process with no lutein detected in portal circulation at any dosage level tested. Our paper also provides insight into how this process can be improved by modifying the typical lipid mixtures carrying the lutein.

Increased Foxp3+Helios+ Regulatory T Cells and Decreased Acute Graft-versus-Host Disease after Allogeneic Bone Marrow Transplantation in Patients Receiving Sirolimus and RGI-2001, an Activator of Invariant Natural Killer T Cells.

Regulatory T (Treg) cells play a central role in immune tolerance and prevention of aberrant immune responses. Several studies have suggested that the risk of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) can be ameliorated by increasing Tregs. We have developed an approach of in vivo expansion of Tregs with RGI-2001, a novel liposomal formulation of a synthetic derivative of alpha-galactosylceramide, a naturally occurring ligand that binds to CD1 and activates and expands invariant natural killer cells. In preclinical studies, a single intravenous infusion of RGI-2001 expanded Treg and could ameliorate GVHD in a mouse model of allogeneic HCT. To explore the role of RGI-2001 in clinical HCT, we initiated a phase 2A clinical trial (n = 29), testing 2 different doses of RGI-2001 administered as a single infusion on day 0 of allogeneic HCT. RGI-2001 was well tolerated and without infusion reactions or cytokine release syndrome. A subset of patients (8 of 29, 28%) responded to RGI-2001 by inducing a markedly increased number of cells with a Treg phenotype. The Treg had a high Ki-67 index and were almost exclusively Helios+ and Foxp3+, indicating that their accumulation was due to expansion of natural Treg. Notably, the incidence of grade 2 to 4 GVHD in the 8 patients who responded to RGI-2001 was 12.5%, compared with 52.4% in the 21 patients who did not respond. No grade 3 or 4 GVHD was observed in the responder group, compared with a 9.5% incidence among nonresponders. Immunosuppression with sirolimus was also associated with a low incidence of GVHD, suggesting that RGI-2001 may have synergized with sirolimus to promote Treg expansion.

Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results.

Ibrutinib, an oral inhibitor of Bruton tyrosine kinase, is approved for patients with mantle cell lymphoma (MCL) who have received one prior therapy. We report the updated safety and efficacy results from the multicenter, open-label phase 2 registration trial of ibrutinib (median 26.7-month follow-up). Patients (N = 111) received oral ibrutinib 560 mg once daily, and those with stable disease or better could enter a long-term extension study. The primary end point was overall response rate (ORR). The median patient age was 68 years (range, 40-84), with a median of 3 prior therapies (range, 1-5). The median treatment duration was 8.3 months; 46% of patients were treated for >12 months, and 22% were treated for ≥2 years. The ORR was 67% (23% complete response), with a median duration of response of 17.5 months. The 24-month progression-free survival and overall survival rates were 31% (95% confidence interval [CI], 22.3-40.4) and 47% (95% CI, 37.1-56.9), respectively. The most common adverse events (AEs) in >30% of patients included diarrhea (54%), fatigue (50%), nausea (33%), and dyspnea (32%). The most frequent grade ≥3 infections included pneumonia (8%), urinary tract infection (4%), and cellulitis (3%). Grade ≥3 bleeding events in ≥2% of patients were hematuria (2%) and subdural hematoma (2%). Common all-grade hematologic AEs were thrombocytopenia (22%), neutropenia (19%), and anemia (18%). The prevalence of infection, diarrhea, and bleeding was highest for the first 6 months of therapy and less thereafter. With longer follow-up, ibrutinib continues to demonstrate durable responses and favorable safety in relapsed/refractory MCL. The trial is registered to www.ClinicalTrials.gov as #NCT01236391.

Monosodium glutamate inhibits the lymphatic transport of lipids in the rat.

It is not well understood how monosodium glutamate (MSG) affects gastrointestinal physiology, especially regarding the absorption and the subsequent transport of dietary lipids into lymph. Thus far, there is little information about how the ingestion of MSG affects the lipid lipolysis, uptake, intracellular esterification, and formation and secretion of chylomicrons. Using lymph fistula rats treated with the infusion of a 2% MSG solution before a continuous infusion of triglyceride, we show that MSG causes a significant decrease in both triglyceride and cholesterol secretion into lymph. Intriguingly, the diminished lymphatic transport of triglyceride and cholesterol was not caused by an accumulation of these labeled lipids in the intestinal lumen or in the intestinal mucosa. Rather, it is a result of increased portal transport in the animals fed acutely the lipid plus 2% MSG in the lipid emulsion. This is a first demonstration of MSG on intestinal lymphatic transport of lipids.

CO2/HCO3(-)- and calcium-regulated soluble adenylyl cyclase as a physiological ATP sensor.

The second messenger molecule cAMP is integral for many physiological processes. In mammalian cells, cAMP can be generated from hormone- and G protein-regulated transmembrane adenylyl cyclases or via the widely expressed and structurally and biochemically distinct enzyme soluble adenylyl cyclase (sAC). sAC activity is uniquely stimulated by bicarbonate ions, and in cells, sAC functions as a physiological carbon dioxide, bicarbonate, and pH sensor. sAC activity is also stimulated by calcium, and its affinity for its substrate ATP suggests that it may be sensitive to physiologically relevant fluctuations in intracellular ATP. We demonstrate here that sAC can function as a cellular ATP sensor. In cells, sAC-generated cAMP reflects alterations in intracellular ATP that do not affect transmembrane AC-generated cAMP. In ß cells of the pancreas, glucose metabolism generates ATP, which corresponds to an increase in cAMP, and we show here that sAC is responsible for an ATP-dependent cAMP increase. Glucose metabolism also elicits insulin secretion, and we further show that sAC is necessary for normal glucose-stimulated insulin secretion in vitro and in vivo.

Comparative Analysis of Bone Regeneration According to Particle Type and Barrier Membrane for Octacalcium Phosphate Grafted into Rabbit Calvarial Defects.

This animal study was aimed to evaluate the efficacy of new bone formation and volume maintenance according to the particle type and the collagen membrane function for grafted octacalcium phosphate (OCP) in rabbit calvarial defects. The synthetic bone substitutes were prepared in powder form with 90% OCP and granular form with 76% OCP, respectively. The calvarial defects were divided into four groups according to the particle type and the membrane application. All specimens were acquired 2 weeks (n = 5) and 8 weeks (n = 5) after surgery. According to the micro-CT results, the new bone volume increased at 2 weeks in the 76% OCP groups compared to the 90% OCP groups, and the bone volume ratio was significantly lower in the 90% OCP group after 2 weeks. The histomorphometric analysis results indicated that the new bone area and its ratio in all experimental groups were increased at 8 weeks except for the group with 90% OCP without a membrane. Furthermore, the residual bone graft area and its ratio in the 90% OCP groups were decreased at 8 weeks. In conclusion, all types of OCP could be applied as biocompatible bone graft materials regardless of its density and membrane application. Neither the OCP concentration nor the membrane application had a significant effect on new bone formation in the defect area, but the higher the OCP concentration, the less graft volume maintenance was needed.

Inter- and intra-session variability of compression strain gauge for the adductor groin squeeze test on soccer athletes.

The importance of hip adductor strength for injury prevention and performance benefits is well documented. The purpose of this study was to establish the intra- and inter-day variability of peak force (PF) of a groin squeeze protocol using a custom-designed compression strain gauge device. Sixteen semi-professional soccer players completed three trials over three separate testing occasions with at least 24-h rest between each session. The main findings were that the compression strain gauge was a reliable device for measuring PF within and between days. All intraclass correlations were higher than 0.80 and coefficients of variations were below 10% across the different sessions and trials. Due to the information gained through the compression strain gauge, the higher sampling frequency utilized, portability, and the relatively affordable price, this device offers an effective alternative for measuring maximal strength for hip adduction.

Prognostic significance of presenting blood pressure in non-ST-segment elevation acute coronary syndrome in relation to prior history of hypertension.

BACKGROUND: Hypertension is a well-established risk factor for cardiovascular disease, whereas low systolic blood pressure (SBP) is a powerful adverse prognosticator in acute coronary syndrome. However, it is unclear whether the prognostic significance of low SBP differs in patients with versus without prior history of hypertension. We sought to investigate the relationships between presenting SBP, prior hypertension, antihypertensive medication use, and outcomes in non-ST-segment elevation acute coronary syndrome (NSTEACS). METHODS: Using data from GRACE/GRACE(2) and CANRACE, we stratified 10,337 patients with NSTEACS from 1999 to 2008 into 2 groups: those with and those without prior diagnosis of hypertension. We performed multivariable logistic regression analysis to assess the prognostic significance of prior hypertension on in-hospital mortality and tested for the interactions between prior hypertension, antihypertensive medication use, and presenting SBP. RESULTS: Compared with patients without prior hypertension (n = 3,732), those with prior hypertension (n = 6,605) were older; more likely to be female; and more frequently had diabetes, previous myocardial infarction, heart failure, renal insufficiency, and higher Killip class and GRACE risk scores on presentation. Patients with prior hypertension were more likely to be on antihypertensive medications before admission, to present with higher SBP, and to have heart failure or cardiogenic shock in hospital (6.0% vs 10.1%; P < .001). In-hospital mortality was higher among patients presenting with lower SBP but did not differ between the groups with and without prior hypertension. In multivariable analysis, neither prior hypertension (adjusted odds ratio = 1.15, 95% CI 0.78-1.70, P = .48) nor the number of antihypertensive medications used (P for trend = .84) was independently associated with in-hospital mortality. In contrast, SBP was a strong independent predictor of in-hospital mortality (adjusted odds ratio = 1.21 per 10 mm Hg lower, 1.15-1.27, P < .001). There was no significant interaction between SBP and prior hypertension (P for interaction = .62) or pre-admission antihypertensive medication use (P for interaction = .46) with respect to in-hospital mortality. CONCLUSION: Low SBP on presentation, but not prior hypertension, was independently associated with in-hospital mortality in NSTEACS. The powerful prognostic value of SBP is similar regardless of a history of hypertension or pre-admission antihypertensive medication use.

Atraumatic versus cutting needles in fluoroscopic lumbar puncture.

OBJECTIVES: Atraumatic needles are known to reduce complication rates of blind lumbar punctures (LP), however, their use in fluoroscopically guided LP is less studied. This study assessed the comparative difficulty of performing fluoroscopic lumbar puncture with atraumatic needles. METHODS: Single-centre retrospective case-control study comparing atraumatic and conventional or "cutting" needles using fluoroscopic time and radiation dose (Dose Area Product or DAP) as surrogate markers. Patients were assessed from two comparable eight-month periods before and after a policy change to primary use of atraumatic needles. RESULTS: 105 procedures with a cutting needle were performed in the group prior to the policy change. Median fluoroscopy time was 48 sec and median DAP was 3.14. Of 102 procedures performed in the group after the policy change, 99 were performed with an atraumatic needle and three with a cutting needle after initial attempt with an atraumatic needle. Median fluoroscopy time was 41 sec and median DAP was 3.28. The mean number of attempts was 1.02 in the cutting needle group and 1.05 in the atraumatic needle group. There was no significant difference in median fluoroscopy time, median DAP, or mean number of attempts. CONCLUSION: Fluoroscopic screening time, DAP and mean number of attempts were not significantly increased with primary use of atraumatic needles for LP. Use of atraumatic needles should be considered in fluoroscopic LP given the lower complication rates. ADVANCES IN KNOWLEDGE: This study provides new data showing that the use of atraumatic needles does not increase the difficulty of fluoroscopically guided LP.

Experiences with Racism Among Asian American Medical Students.

Importance: Asian American physicians have experienced a dual pandemic of racism and COVID-19 since 2020; understanding how racism has affected the learning environment of Asian American medical students is necessary to inform strategies to promoting a more inclusive medical school environment and a diverse and inclusive workforce. While prior research has explored the influence of anti-Asian racism on the experiences of Asian American health care workers, to our knowledge there are no studies investigating how racism has impacted the training experiences of Asian American medical students. Objective: To characterize how Asian American medical students have experienced anti-Asian racism in a medical school learning environment. Design, Setting, and Participants: This qualitative study included online video interviews of Asian American medical students performed between July 29, 2021, and August 22, 2022. Eligible participants were recruited through the Asian Pacific American Medical Students Association and snowball sampling, and the sample represented a disaggregated population of Asian Americans and all 4 medical school years. Main Outcomes and Measures: The medical school experiences of Asian American medical students. Results: Among 25 participants, Asian ethnicities included 8 Chinese American (32%), 5 Korean American (20%), 5 Indian American (20%), 3 Vietnamese American (12%), 2 Filipino American (8%), and 1 (4%) each Nepalese, Pakistani, and Desi American; 16 (64%) were female. Participants described 5 major themes concerning their experience with discrimination: (1) invisibility as racial aggression (eg, "It took them the whole first year to be able to tell me apart from the other Asian guy"); (2) visibility and racial aggression ("It transitioned from these series of microaggressions that every Asian person felt to actual aggression"); (3) absence of the Asian American experience in medical school ("They're not going to mention Asian Americans at all"); (4) ignored while seeking support ("I don't know what it means to have this part of my identity supported"); and (5) envisioning the future. Conclusions and Relevance: In this qualitative study, Asian American medical students reported feeling invisible within medical school while a target of anti-Asian racism. Addressing these unique challenges related to anti-Asian racism is necessary to promote a more inclusive medical school learning environment.

Decentralized clinical trial design using blood microsampling technology for serum bioanalysis.

Background: Alternatives to phlebotomy in clinical trials increase options for patients and clinicians by simplifying and increasing accessibility to clinical trials. The authors investigated the technical and logistical considerations of one technology compared with phlebotomy. Methodology: Paired samples were collected from 16 donors via a second-generation serum gel microsampling device and conventional phlebotomy. Microsamples were subject to alternative sample handling conditions and were evaluated for quality, clinical testing and proteome profiling. Results: Timely centrifugation of blood serum microsamples largely preserved analyte stability. Conclusion: Centrifugation timing of serum microsamples impacts the quality of specific clinical chemistry and protein biomarkers. Microsampling devices with remote centrifugation and refrigerated shipping can decrease patient burden, expand clinical trial populations and aid clinical decisions.

Blueprint for antibody biologics developability.

Large-molecule antibody biologics have revolutionized medicine owing to their superior target specificity, pharmacokinetic and pharmacodynamic properties, safety and toxicity profiles, and amenability to versatile engineering. In this review, we focus on preclinical antibody developability, including its definition, scope, and key activities from hit to lead optimization and selection. This includes generation, computational and in silico approaches, molecular engineering, production, analytical and biophysical characterization, stability and forced degradation studies, and process and formulation assessments. More recently, it is apparent these activities not only affect lead selection and manufacturability, but ultimately correlate with clinical progression and success. Emerging developability workflows and strategies are explored as part of a blueprint for developability success that includes an overview of the four major molecular properties that affect all developability outcomes: 1) conformational, 2) chemical, 3) colloidal, and 4) other interactions. We also examine risk assessment and mitigation strategies that increase the likelihood of success for moving the right candidate into the clinic.

Photo-crosslinked gelatin methacryloyl hydrogel strengthened with calcium phosphate-based nanoparticles for early healing of rabbit calvarial defects.

PURPOSE: The aim of this study was to investigate the efficacy of photo-crosslinked gelatin methacryloyl (GelMa) hydrogel containing calcium phosphate nanoparticles (CNp) when applying different fabrication methods for bone regeneration. METHODS: Four circular defects were created in the calvaria of 10 rabbits. Each defect was randomly allocated to the following study groups: 1) the sham control group, 2) the GelMa group (defect filled with crosslinked GelMa hydrogel), 3) the CNp-GelMa group (GelMa hydrogel crosslinked with nanoparticles), and 4) the CNp+GelMa group (crosslinked GelMa loaded with nanoparticles). At 2, 4, and 8 weeks, samples were harvested, and histological and micro-computed tomography analyses were performed. RESULTS: Histomorphometric analysis showed that the CNp-GelMa and CNp+GelMa groups at 2 weeks had significantly greater total augmented areas than the control group (P<0.05). The greatest new bone area was observed in the CNp-GelMa group, but without statistical significance (P>0.05). Crosslinked GelMa hydrogel with nanoparticles exhibited good biocompatibility with a minimal inflammatory reaction. CONCLUSIONS: There was no difference in the efficacy of bone regeneration according to the synthesized method of photo-crosslinked GelMa hydrogel with nanoparticles. However, these materials could remain within a bone defect up to 2 weeks and showed good biocompatibility with little inflammatory response. Further improvement in mechanical properties and resistance to enzymatic degradation would be needed for the clinical application.

Effect of peripheral administration of cholecystokinin on food intake in apolipoprotein AIV knockout mice.

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are satiation factors secreted by the small intestine in response to lipid meals. Apo AIV and CCK-8 has an additive effect to suppress food intake relative to apo AIV or CCK-8 alone. In this study, we determined whether CCK-8 (1, 3, or 5 µg/kg ip) reduces food intake in fasted apo AIV knockout (KO) mice as effectively as in fasted wild-type (WT) mice. Food intake was monitored by the DietMax food system. Apo AIV KO mice had significantly reduced 30-min food intake following all doses of CCK-8, whereas WT mice had reduced food intake only at doses of 3 µg/kg and above. Post hoc analysis revealed that the reduction of 10-min and 30-min food intake elicited by each dose of CCK-8 was significantly larger in the apo AIV KO mice than in the WT mice. Peripheral CCK 1 receptor (CCK1R) gene expression (mRNA) in the duodenum and gallbladder of the fasted apo AIV KO mice was comparable to that in WT mice. In contrast, CCK1R mRNA in nodose ganglia of the apo AIV KO mice was upregulated relative to WT animals. Similarly, upregulated CCK1R gene expression was found in the brain stem of apo AIV KO mice by in situ hybridization. Although it is possible that the increased satiating potency of CCK in apo AIV KO mice is mediated by upregulation of CCK 1R in the nodose ganglia and nucleus tractus solitarius, additional experiments are required to confirm such a mechanism.

Rheumatology expertise in advising immunocompromised healthcare workers: Insights from a survey of Australian rheumatologists.

BACKGROUND: Healthcare workers (HCW) with an inflammatory disease may be at increased risk of infections and their complications, however there is no evidence to guide specific measures to reduce the risk of immunocompromised HCW acquiring infection in the workplace. This cross-sectional study aimed to define the attitudes of rheumatologists and rheumatology trainees towards counselling immunocompromised healthcare workers about additional workplace precautions to minimise workplace risk of infection. METHODS: A cross-sectional survey was administered via Zoom poll during a webinar held in August 2020. Participants were Victorian and Tasmanian members of the Australian Rheumatology Association, which includes consultant rheumatologists and rheumatology trainees. Descriptive statistics were used to analyse survey responses. RESULTS: Of the 52 participants, 41 provided care to at least one immunocompromised healthcare worker. 21 out of 52 participants estimated that the majority of these patients sought their advice about infection risk in the workplace. The most common source of information for counselling patients on workplace infection risks were colleagues (38/50). Participants were most confident in providing information on influenza and hepatitis but less confident in providing information in tuberculosis, shingles and COVID-19. Most participants believed employers of immunocompromised HCW should play a role in providing advice on managing infection risks in the workplace. CONCLUSION: Our study reveals a level of uncertainty and discomfort amongst rheumatologists in providing recommendations to immunocompromised healthcare workers about managing their workplace risk of infection. We recommend the development of a framework to guide the clinician in making individualised recommendations for immunocompromised HCW.

Three-dimensionally printed biphasic calcium phosphate blocks with different pore diameters for regeneration in rabbit calvarial defects.

BACKGROUND: Biphasic calcium phosphate (BCP) is the most frequently used synthetic bone substitutes, which comprises a combination of hydroxyapatite (HA) and beta-tricalcium phosphate (b-TCP). Thanks to the recent advances in digital dentistry and three-dimensional (3D) printing technology, synthetic block bone substitutes can be customized to fit individual defect morphologies. The diameter of the pores can influence the rate of bone formation and material resorption. The aim of this study was to compare three-dimensionally printed biphasic calcium phosphate (BCP) block bone substitutes with different pore diameters (0.8-, 1.0-, and 1.2- mm) for use in the regeneration of rabbit calvarial defects. METHODS: Four circular defects were formed on the calvaria of ten rabbits. Each defect was randomly allocated to one of the following study groups: (i) control group, (ii) 0.8-mm group, (iii) 1.0-mm group, and (iv) 1.2-mm group. All specimens were postoperatively harvested at 2 and 8 weeks, and radiographic and histomorphometric analyses were performed on the samples. RESULTS: Histologically, the BCP blocks remained unresorbed up to 8 weeks, and new bone formation occurred within the porous structures of the blocks. After the short healing period of 2 weeks, histomorphometric analysis indicated that new bone formation was significantly greater in the BCP groups compared with the control (p < 0.05). However, there were no significant differences between the groups with different pore diameters (p > 0.05). At 8 weeks, only the 1.0-mm group (3.42 ± 0.48 mm2, mean ± standard deviation) presented a significantly larger area of new bone compared with the control (2.26 ± 0.59 mm2) (p < 0.05). Among the BCP groups, the 1.0- and 1.2-mm groups exhibited significantly larger areas of new bone compared with the 0.8-mm group (3.42 ± 0.48 and 3.04 ± 0.66 vs 1.60 ± 0.70 mm2, respectively). CONCLUSIONS: Within the limitations of this study, the BCP block bone substitutes can be applied to bone defects for successful bone regeneration. Future studies should investigate more-challenging defect configurations prior to considering clinical applications.