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1.
J Sports Sci Med ; 22(4): 688-699, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38045746

ABSTRACT

The objective of this study was to explore the effects of three weekly frequency doses of high-intensity functional training (HIFT) on an array of cardiometabolic markers in adults with metabolic syndrome (MetS). Twenty-one men and women, randomized into one (HIFT1), two (HIFT2), or three (HIFT3) days per week of HIFT, completed 3-weeks of familiarization plus a 12-week progressive training program. Pre- and post-intervention, several cardiometabolic, body composition, oxygen consumption, metabolic syndrome severity, and perceptions of fitness measurements were assessed. Additionally, an exercise enjoyment survey was administered post-intervention. A Cohen's d was used to demonstrate within-group change effect size. Although this study was not fully powered, a one-way and two-way ANOVA were used to compare the dose groups to provide provisional insights. No differences were found when frequency dose groups were compared. Many cardiometabolic, body composition, and fitness improvements were seen within each group, with clinically meaningful improvements in the metabolic syndrome severity score (MSSS) (HIFT1: -0.105, d = 0.28; HIFT2: -0.382, d = 1.20; HIFT3: -0.467, d = 1.07), waist circumference (HIFT1: -4.1cm, d = 3.33; HIFT2: -5.4cm, d = 0.89; HIFT3: -0.7cm, d = 0.20), and blood glucose (HIFT1: -9.5mg/dL, d = 0.98; HIFT2: -4.9mg/dL, d = 1.00; HIFT3: -1.7mg/dL, d = 0.23). All three groups similarly reported high exercise enjoyment and likeliness to continue after the intervention. In conclusion, HIFT performed once, twice, or thrice a week elicits improvements in MetS and is considered enjoyable. HIFT, even at a low weekly dose, therefore represents a potential strategy to reduce the global MetS burden.


Subject(s)
Cardiovascular Diseases , High-Intensity Interval Training , Metabolic Syndrome , Adult , Male , Humans , Female , Metabolic Syndrome/prevention & control , Pleasure , Analysis of Variance
2.
South Med J ; 116(12): 930-937, 2023 12.
Article in English | MEDLINE | ID: mdl-38051165

ABSTRACT

OBJECTIVES: Southern Appalachia is a region of the United States that is disproportionately affected by the opioid epidemic and by increasing rates of neonatal abstinence syndrome (NAS). NAS rates increased approximately 400% between 1999 and 2012. Buprenorphine prescriptions written to treat opioid use disorder also increased dramatically. The present study was undertaken to ascertain any relationship between the number of buprenorphine prescriptions compared with NAS rates in southern Appalachia. METHODS: A total of 250 southern Appalachian counties across seven states, including all of West Virginia and portions of Virginia, Kentucky, Maryland, North Carolina, Ohio, and Tennessee were identified. A retrospective cohort analysis of these counties was conducted for the years 2005-2018. All of the data were obtained from publicly accessible sources or direct communication with government offices. Measures from each county in southern Appalachia included annual NAS rates, buprenorphine prescription rates, drug-induced death rates, and opioid prescribing rates. Associations among these variables were examined using a generalized linear regression. RESULTS: Significant linear associations exist between the rising rate of NAS diagnoses and the rising rate of buprenorphine prescriptions (r = 0.977, R2 = 95.53%, P < 0.001) and between the rising rate of buprenorphine prescriptions and the increase in drug-induced deaths (r = 0.712, R2 = 50.82%, P = 0.031). CONCLUSIONS: This is the first report that documents an association between rising NAS rates and increasing buprenorphine prescribing. Between the years 2010 and 2018, the NAS rate in southern Appalachia rose by 335%, and the number of buprenorphine prescriptions rose by 413%. Discussions regarding the current policies for buprenorphine management during pregnancy are warranted. We suggest a reevaluation of buprenorphine prescribing recommendations during pregnancy and further research on establishing the lowest effective buprenorphine dose for each pregnant patient.


Subject(s)
Buprenorphine , Neonatal Abstinence Syndrome , Opioid-Related Disorders , Pregnancy Complications , Pregnancy , Female , Infant, Newborn , United States , Humans , Buprenorphine/therapeutic use , Analgesics, Opioid/therapeutic use , Retrospective Studies , Neonatal Abstinence Syndrome/drug therapy , Neonatal Abstinence Syndrome/epidemiology , Practice Patterns, Physicians' , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/epidemiology , Prescriptions , Pregnancy Complications/drug therapy
3.
J Wildl Dis ; 59(4): 804-806, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37486877

ABSTRACT

A Common Loon (Gavia immer) was found recumbent at Island Beach State Park, New Jersey, US, and euthanized. Necropsy revealed a caseous mass in the kidney, from which bacteria were isolated and phenotypically and molecularly identified as Edwardsiella tarda.


Subject(s)
Birds , Edwardsiella tarda , Animals , Kidney , Autopsy/veterinary , New Jersey
4.
J Wildl Dis ; 59(2): 234-244, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36996083

ABSTRACT

A popular species in the pet trade, and therefore in the illegal wildlife trade, the diamond-backed terrapin, Malaclemys terrapin terrapin, population has seen significant declines. Associated with the illegal wildlife trade, occasions arise in which terrapins are confiscated, and no standard operating procedures exist for repatriation into the wild. To develop such procedures, an understanding of the pathogens circulating in the wild diamond-backed terrapin population in New Jersey is needed. We sampled 30 wild female diamond-backed terrapins for herpesvirus, Mycoplasmopsis, ranavirus, and intestinal and blood parasites and performed white blood cell counts and differentials and evaluated biochemistry values. Terrapins had an average age of 10 yr (8-15 yr), and 70% were gravid at the time of sampling. Thirty-three percent of the sampled northern diamond-backed terrapins were positive for Mycoplasmopsis sp., and all were negative for ranavirus and herpesviruses. Occasional blood parasites were found, and few intestinal parasites were noted. There was no significant difference between gravid status and any of the blood parameters (P<0.05). Blood chemistry values appeared to vary according to feeding activity; no differences were noted in the values in relation to gravid status. Four terrapins had heterophil to lymphocyte (H:L) ratios above 4.5, significantly higher than the other terrapins sampled, which may indicate inflammation. Two of the four had Mycoplasmopsis, one sample was contaminated by other bacteria and was discarded, and one was negative. No significant difference was found between Mycoplasmopsis infection status and H:L ratio (P=0.926). Our findings, though conducted on a small number of female terrapins at a specific time point, provide data on the pathogens that may be circulating in this population, adding to the current body of knowledge and helping to guide decision making for the reintroduction of confiscated diamond-backed terrapins into New Jersey's wild population.


Subject(s)
Turtles , Female , Animals , New Jersey/epidemiology
5.
Sci Adv ; 9(5): eadc9465, 2023 02 03.
Article in English | MEDLINE | ID: mdl-36735787

ABSTRACT

High levels of lactate are positively associated with the prognosis and mortality in patients with heart attack. Endothelial-to-mesenchymal transition (EndoMT) plays an important role in cardiac fibrosis. Here, we report that lactate exerts a previously unknown function that increases cardiac fibrosis and exacerbates cardiac dysfunction by promoting EndoMT following myocardial infarction (MI). Treatment of endothelial cells with lactate disrupts endothelial cell function and induces mesenchymal-like function following hypoxia by activating the TGF-ß/Smad2 pathway. Mechanistically, lactate induces an association between CBP/p300 and Snail1, leading to lactylation of Snail1, a TGF-ß transcription factor, through lactate transporter monocarboxylate transporter (MCT)-dependent signaling. Inhibiting Snail1 diminishes lactate-induced EndoMT and TGF-ß/Smad2 activation after hypoxia/MI. The MCT inhibitor CHC mitigates lactate-induced EndoMT and Snail1 lactylation. Silence of MCT1 compromises lactate-promoted cardiac dysfunction and EndoMT after MI. We conclude that lactate acts as an important molecule that up-regulates cardiac EndoMT after MI via induction of Snail1 lactylation.


Subject(s)
Endothelial Cells , Myocardial Infarction , Humans , Endothelial Cells/metabolism , Lactic Acid , Transforming Growth Factor beta/metabolism , Myocardial Infarction/metabolism , Hypoxia/metabolism , Fibrosis
6.
Animals (Basel) ; 12(15)2022 Aug 05.
Article in English | MEDLINE | ID: mdl-35953971

ABSTRACT

The cattle breeding industry, through both of its derivatives (dairy and beef), provides 81% of milk and 22% of meat required globally. If a breeding bull is sub-fertile, this impacts herd conception and birth rates, and it is generally accepted that having a proactive genetic screening programme can prevent further losses. Chromosome translocations are the leading genetic cause of infertility in livestock and, in cattle, this extends beyond the classical 1:29 to other Robertsonian translocations (RobTs) and to reciprocal translocations (RECTs). The incidence of both (collectively termed RTs) varies between breeds and herds; however, we estimate that RECTs are, most likely, at least twice as common as RobTs. The purpose of this study was to develop an industry economic model to estimate the financial impact of an RT event at the herd level. If we assume a conservative incidence rate of 0.4% for Rob1:29 with each one impacting the conception rate by 5%, we calculate that actively screening for and removing a Rob1:29 bull could benefit an impacted herd by GBP 2.3 million (approx. USD 2.8 million) over six years. A recently updated screening protocol developed in our lab for all RTs, however (with a projected combined incidence of 1.2%, impacting conception rates by 10%), could benefit an impacted herd by GBP 7.2 million (nearly USD 9 million) for each RT found. For an industry worth USD 827.4 billion (dairy) and USD 467.7 billion (beef), expanding knowledge on incidence and further dissection of the potential costs (financial and environmental) from RTs is essential to prevent further losses.

7.
Front Immunol ; 13: 872652, 2022.
Article in English | MEDLINE | ID: mdl-35693816

ABSTRACT

Aging plays a critical role in the incidence and severity of infection, with age emerging as an independent predictor of mortality in sepsis. Trained immunity reprograms immunocytes to respond more rapidly and effectively to pathogens and serves as a potential approach to improve immune function in aging and/or sepsis. However, there is very little data on trained immunity in the aging immune system or in the presence of sepsis. We examined the impact of ß-glucan induced innate immune training on monocytes from aging healthy humans (>60 years old) as well as sepsis patients. We observed increased metabolic capacity, upregulated cytokine secretion, increased H3K27 acetylation, and upregulation of crucial intracellular signaling pathways in trained monocytes from healthy aging subjects. The response to trained immunity in healthy aging monocytes was equivalent to the response of monocytes from younger, i.e., 18 - 59 years, individuals. Additionally, we found that trained immunity induced a unique expression pattern of cell surface markers in monocytes that was consistent across age groups. Trained monocytes from sepsis patients also displayed enhanced metabolic capacity and increased cytokine production. These results indicate that immune training can be induced in aging monocytes as well as monocytes from critically ill sepsis patients.


Subject(s)
Sepsis , beta-Glucans , Cytokines/metabolism , Humans , Middle Aged , Monocytes , Signal Transduction , beta-Glucans/pharmacology
8.
Article in English | MEDLINE | ID: mdl-35452747

ABSTRACT

Major depressive disorder (MDD) and suicide have been associated with elevated indices of oxidative damage in the brain, as well as white matter pathology including reduced myelination by oligodendrocytes. Oligodendrocytes highly populate white matter and are inherently susceptible to oxidative damage. Pathology of white matter oligodendrocytes has been reported to occur in brain regions that process behaviors that are disrupted in MDD and that may contribute to suicidal behavior. The present study was designed to determine whether oligodendrocyte pathology related to oxidative damage extends to brain areas outside of those that are traditionally considered to contribute to the psychopathology of MDD and suicide. Relative telomere lengths and the gene expression of five antioxidant-related genes, SOD1, SOD2, GPX1, CAT, and AGPS were measured in oligodendrocytes laser captured from two non-limbic brain areas: occipital cortical white matter and the brainstem locus coeruleus. Postmortem brain tissues were obtained from brain donors that died by suicide and had an active MDD at the time of death, and from psychiatrically normal control donors. Relative telomere lengths were significantly reduced in oligodendrocytes of both brain regions in MDD donors as compared to control donors. Three antioxidant-related genes (SOD1, SOD2, GPX1) were significantly reduced and one was significantly elevated (AGPS) in oligodendrocytes from both brain regions in MDD as compared to control donors. These findings suggest that oligodendrocyte pathology in MDD and suicide is widespread in the brain and not restricted to brain areas commonly associated with depression psychopathology.


Subject(s)
Depressive Disorder, Major , Suicide , Antioxidants/metabolism , Depressive Disorder, Major/metabolism , Humans , Locus Coeruleus/metabolism , Occipital Lobe , Oligodendroglia/metabolism , Oxidative Stress , Superoxide Dismutase-1/metabolism
10.
Am J Hosp Palliat Care ; 39(11): 1281-1287, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35234074

ABSTRACT

BACKGROUND: New opportunities to expand home-based palliative care (HBPC) highlight the need for novel data that explores how HBPC providers currently navigate this nascent business. OBJECTIVES: To investigate how HBPC providers and their organizations sustain their operations in a rapidly evolving market. STUDY DESIGN: This was an exploratory, qualitative study. SETTING: We conducted focus groups with staff of nine HBPC organizations that held provider contracts with a large California insurance provider. MEASUREMENT: A research team member experienced in qualitative methods conducted semi-structured focus group interviews with HBPC agency staff who were knowledgeable about their agency's patient recruitment and enrollment processes. Interview sessions of roughly an hour long were audio-recorded and transcribed verbatim. We used thematic analysis procedures to identify codes and themes. RESULTS: We identified seven themes: market competition, market diversity, HBPC reimbursement, service standardization, hiring practices, marketing, strategic enrollment processes, and outcomes monitoring. The participants called for more standardization in their field. In discussing key business operations-hiring, marketing, patient enrollment, outcomes monitoring-they demonstrated inventiveness and willingness to innovate in order to succeed in a complex healthcare sector. CONCLUSION: Our study expands on the literature by providing a glimpse of the challenges encountered by HBPC providers and their organizations and the myriad strategies they undertake to navigate a health-service area that lacks standardized practice and payment guidelines. Our findings suggest that HBPC agencies will continue to struggle in the absence of standardization in practice, payment, and quality oversight.


Subject(s)
Home Care Services , Palliative Care , Humans , Primary Health Care , Qualitative Research , United States , United States Department of Veterans Affairs
11.
J Pain Symptom Manage ; 63(5): 665-672, 2022 05.
Article in English | MEDLINE | ID: mdl-35081443

ABSTRACT

CONTEXT: As funding for home-based palliative care continues to expand, there is an increasing need to understand barriers to patient referral to and acceptance of home-based palliative care. OBJECTIVES: The aim of this study was to elicit perspectives of home-based palliative care administrators and providers on barriers encountered in identification, referral, and enrollment of patients eligible for home-based palliative care. METHODS: We conducted a qualitative study employing focus groups of nine home-based palliative care agencies across California. Focus groups were audio-recorded and transcribed. Using thematic analysis, researchers independently coded the transcripts and identified themes from the codes. RESULTS: A total of 25 HBPC staff participated in the nine focus groups. Participants included both clinicians (n = 17) and administrators (n = 8). Our analysis revealed 13 themes that fit under four major thematic categories: 1) lack of formal payment structures (few HBPC payors and variation in payment and services among payors), 2) agency structure barriers (limitations of electronic medical records and multiple lines of business), 3) patient- and family-level barriers (misconceptions and/or lack of palliative care knowledge, uninformed of the referral and/or no warm hand-off, reluctance to have strangers in the home, overwhelmed with health issues and related services, HBPC service refusal/unresponsive to outreach), and 4) physician-level barriers (misconceptions and/or lack of palliative care knowledge, variability in HBPC payment and services, lack of time, patient ownership). CONCLUSION: HBPC providers identified a myriad of barriers that preclude patient access to HBPC. With growing provision of HBPC services, greater efforts to overcome these barriers are needed.


Subject(s)
Home Care Services , Hospice and Palliative Care Nursing , Humans , Palliative Care , Qualitative Research , Referral and Consultation
12.
Parasitol Res ; 120(11): 3709-3723, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34599358

ABSTRACT

Anadromous river herring have declined in many parts of their range, leading to fisheries management efforts to help repopulate this species by improving connectivity of rivers and restoring populations by fish transfers. With data lacking on parasites in these species, this study sought to better understand myxozoans across various life stages and habitats in river herring populations in New Jersey, USA. We compared fish from riverine habitats during early-life growth and adults returning to spawn, marine-phase fish, and landlocked Alewife populations. Three myxozoan species were identified in young-of-the-year (YOY) anadromous river herring, including Kudoa clupeidae in the skeletal musculature, Myxobolus mauriensis in the rib cartilage, and an uncharacterized coelozoic myxozoan within the lumen of mesonephric tubules. In YOY river herring, Blueback Herring were 2 times more likely to be infected by K. clupeidae than Alewife (p = 0.019) and in the Maurice River, fish were 4 times more likely to be infected with M. mauriensis than fish from Great Egg Harbor River (p = 0.000) and 11 times more likely than the Delaware River (p = 0.001). Spawning adult river herring were infected with a previously undescribed myxozoan parasite infecting the kidney. Sequencing the 18S rDNA indicated this species is closely related to Ortholinea species. Myxobolus mauriensis and the Ortholinea-like species were absent from marine-phase river herring indicating that infections were linked to river environments occurring during early-life growth and spawning, respectively. No myxozoans were present in landlocked Alewife, showing that similar infections occurring in rivers were absent in lake environments in the region.


Subject(s)
Fish Diseases , Parasites , Animals , Ecosystem , Fish Diseases/epidemiology , Fishes , Life Cycle Stages , Rivers
13.
Public Health Nutr ; 23(16): 2857-2863, 2020 11.
Article in English | MEDLINE | ID: mdl-32576300

ABSTRACT

OBJECTIVE: To compare the sugar content of items at four multinational fast-food chains, across three countries. DESIGN: Total sugar (g)/per serving was extracted from online nutrition information, and sugar/100 g serving was calculated. Foods were categorised as: breakfast sandwiches, burgers, sandwiches, desserts and condiments. Beverages were categorised as fountain, frozen or pre-packaged. Sugar (g) was compared across countries using linear mixed-effects models. Pairwise comparisons were performed with Tukey-Kramer adjustments. SETTING: USA, Germany and Australia. PARTICIPANTS: Burger King™ (Hungry Jack's™), Kentucky Fried Chicken™, McDonald's™ and Subway™. RESULTS: Differences in total sugar/100 g or ml were observed across countries for burgers (n 104), desserts (n 110), sandwiches (n 178), pre-packaged beverages (n 36) and frozen beverages (n 72). Comparing identical items across countries (e.g. BigMacTM from McDonalds in USA, Germany and Australia), burgers (n 10 available in all three countries) had lower sugar content in Australia (3·4 g/100 g) compared with the USA (4·7 g/100 g, P = 0·02) or Germany (4·6 g/100 g, P = 0·04), yet no differences were observed in other food categories. Comparing the same beverages across countries (e.g. chocolate shake from Burger King), frozen beverages (n 4 available in all three countries) had lower sugar content in Australia (14·2 g/100 ml), compared with the USA (20·3 g/100 ml, P = 0·0005) or Germany (17·8 g/100 ml, P = 0·0148), yet no differences were observed in other beverage categories. CONCLUSIONS: Heterogeneity in fast-food sugar content across countries suggests that reductions are possible and should be implemented to reduce health risks associated with excess added sugar intake.


Subject(s)
Fast Foods , Sugars , Australia , Beverages/analysis , Fast Foods/analysis , Food Labeling , Germany , Humans , Sugars/analysis , United States
14.
BMC Med Educ ; 20(1): 173, 2020 May 29.
Article in English | MEDLINE | ID: mdl-32471490

ABSTRACT

BACKGROUND: Aboriginal cultural awareness training aims to build a culturally responsive workforce, however research has found the training has limited impact on the health professional's ability to provide culturally safe care. This study examined cultural awareness training feedback from healthcare professionals working with high Aboriginal patient caseloads in the Top End of the Northern Territory of Australia. The aim of the research was to assess the perception of training and the potential for expansion to better meet workforce needs. METHODS: Audit and qualitative thematic analysis of cultural awareness training evaluation forms completed by course participants between March and October 2018. Course participants ranked seven teaching domains using five-point Likert scales (maximum summary score 35 points) and provided free-text feedback. Data were analysed using the Framework Method and assessed against Kirkpatrick's training evaluation model. Cultural safety and decolonising philosophies shaped the approach. RESULTS: 621 participants attended 27 ACAP sessions during the study period. Evaluation forms were completed by 596 (96%). The mean overall assessment score provided was 34/35 points (standard deviation 1.0, range 31-35) indicating high levels of participant satisfaction. Analysis of 683 free text comments found participants wanted more cultural education, designed and delivered by local people, which provides an opportunity to consciously explore both Aboriginal and non-Aboriginal cultures (including self-reflection). Regarding the expansion of cultural education, four major areas requiring specific attention were identified: communication, kinship, history and professional relevance. A strength of this training was the authentic personal stories shared by local Aboriginal cultural educators, reflecting community experiences and attitudes. Criticism of the current model included that too much information was delivered in one day. CONCLUSIONS: Healthcare providers found cultural awareness training to be an invaluable entry point. Cultural education which elevates the Aboriginal health user's experience and provides health professionals with an opportunity for critical self-reflection and practical solutions for common cross-cultural clinical encounters may improve the delivery of culturally safe care. We conclude that revised models of cultural education should be developed, tested and evaluated. This requires institutional support, and recognition that cultural education can contribute to addressing systemic racism.


Subject(s)
Cultural Competency/education , Health Personnel/education , Health Services, Indigenous , Australia , Hospitals , Humans , Native Hawaiian or Other Pacific Islander
16.
J Fish Dis ; 42(12): 1697-1711, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31617232

ABSTRACT

Wild bluegill, Lepomis macrochirus Rafinesque, succumb to seasonal mortality in the early spring during cool water temperatures, shown previously to be related to bacteraemia caused by a psychrotrophic bacterium, Pseudomonas mandelii. In the study herein, intestinal coccidiosis in wild bluegill had seasonal prevalence causing heavy intestinal infections and sloughing of intestinal epithelium occurring in late winter/early spring. Infections were predominantly related to two different species, Goussia washuti n. sp., an epicellular coccidium, and a coccidium closely resembling Goussia desseri Molnár 1996, previously only described in percid fish in Europe. In 2019, co-infections of bacteraemia and intestinal coccidiosis occurred in bluegills. Evaluating coccidium infection intensity by fresh parasite examination and histology, an association was observed in which fish with moderate-to-heavy intestinal coccidiosis were 8-12 times more likely to have bacteraemia compared to fish with no or light coccidiosis. The association of these co-infections suggests that intestinal coccidiosis could contribute to seasonal bacterial epizootics of wild bluegill.


Subject(s)
Coccidiosis/diagnosis , Fish Diseases/microbiology , Fish Diseases/parasitology , Intestinal Diseases, Parasitic/veterinary , Perciformes/parasitology , Pseudomonas Infections/veterinary , Seasons , Animals , Bacteremia/mortality , Bacteremia/veterinary , Coccidiosis/microbiology , Coccidiosis/pathology , Cold Temperature , Fish Diseases/mortality , Intestinal Diseases, Parasitic/diagnosis , Intestinal Diseases, Parasitic/microbiology , Perciformes/microbiology , Pseudomonas/pathogenicity , Pseudomonas Infections/mortality , Pseudomonas Infections/parasitology
17.
J Infect Dis ; 220(3): 411-419, 2019 07 02.
Article in English | MEDLINE | ID: mdl-31535143

ABSTRACT

BACKGROUND: A conditionally replication-defective human cytomegalovirus (CMV) vaccine (V160) derived from AD169 and genetically engineered to express CMV pentameric complex (gH/gL/pUL128/pUL130/pUL131) was developed and evaluated for phase 1 vaccine safety and immunogenicity in CMV-seronegative and CMV-seropositive adults. METHODS: Subjects received 3 doses of V160 or placebo on day 1, month 1, and month 6. Four vaccine dose levels, formulated with or without aluminum phosphate adjuvant, were evaluated. Injection-site and systemic adverse events (AEs) and vaccine viral shedding were monitored. CMV-specific cellular and humoral responses were measured by interferon-gamma ELISPOT and virus neutralization assay up to 12 months after last dose. RESULTS: V160 was generally well-tolerated, with no serious AEs observed. Transient, mild-to-moderate injection-site and systemic AEs were reported more frequently in vaccinated subjects than placebo. Vaccine viral shedding was not detected in any subject, confirming the nonreplicating feature of V160. Robust neutralizing antibody titers were elicited and maintained through 12 months postvaccination. Cellular responses to structural and nonstructural viral proteins were observed, indicating de novo expression of viral genes postvaccination. CONCLUSIONS: V160 displayed an acceptable safety profile. Levels of neutralizing antibodies and T-cell responses in CMV-seronegative subjects were within ranges observed following natural CMV infection. CLINICAL TRIAL REGISTRATION: . NCT01986010.


Subject(s)
Cytomegalovirus Infections/immunology , Cytomegalovirus Vaccines/immunology , Cytomegalovirus/immunology , Virus Replication/immunology , Adjuvants, Immunologic/administration & dosage , Adolescent , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Double-Blind Method , Enzyme-Linked Immunospot Assay/methods , Female , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunization/methods , Male , Middle Aged , T-Lymphocytes/immunology , Vaccination/methods , Virus Shedding/immunology , Young Adult
18.
Antivir Ther ; 24(4): 301-308, 2019.
Article in English | MEDLINE | ID: mdl-30896438

ABSTRACT

BACKGROUND: Cabotegravir (CAB) is an integrase strand transfer inhibitor in development as a long-acting injectable formulation, with an oral formulation used during a safety lead-in period. Tuberculosis (TB)-HIV coinfection is common, often requiring simultaneous treatment. Rifabutin (RBT) is an alternative antimycobacterial agent for TB and a moderate inducer of cytochrome P450 and UDP-glucuronosyltransferase isoenzymes. This study evaluated the impact of RBT on the pharmacokinetics (PK) of oral CAB. METHODS: In this Phase I, single-centre, open-label, two-period, fixed-sequence, drug interaction study, subjects received oral CAB 30 mg once daily for 14 days in period 1, and oral CAB plus RBT 300 mg once daily for 14 days in period 2. Serial PK sampling was performed on days 14 and 28. Geometric least squares (GLS) mean ratios with associated 90% CIs were calculated to compare CAB noncompartmental PK parameters following CAB+RBT versus CAB alone. Safety was also assessed. RESULTS: A total of 15 male subjects were enrolled and 12 completed all treatments. Comparing CAB+RBT with CAB alone, the GLS mean ratios (90% CIs) for CAB area under the concentration-time curve from time zero to the end of the dosing interval (AUC0-τ), maximum observed plasma concentration (Cmax) and concentration at the end of the dosing interval (Cτ) were 0.79 (0.74, 0.83), 0.83 (0.76, 0.90) and 0.74 (0.70, 0.78), respectively. 11 subjects reported 24 adverse events (AEs); 22 were reported with CAB+RBT (3 drug-related) and 2 with CAB alone (not drug-related). All AEs resolved by study end. CONCLUSIONS: RBT had a modest impact on plasma CAB exposure following oral coadministration, resulting in overall plasma CAB trough exposures above the 10 mg oral dose shown to maintain viral suppression in HIV-1-infected subjects. Oral CAB can be coadministered with RBT without dosage adjustment.


Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-HIV Agents/pharmacokinetics , Pyridones/pharmacokinetics , Rifabutin/pharmacology , Administration, Oral , Adolescent , Adult , Aged , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , Drug Interactions , Female , Healthy Volunteers , Humans , Male , Middle Aged , Pyridones/administration & dosage , Pyridones/adverse effects , Young Adult
19.
Perm J ; 23: 18-041, 2019.
Article in English | MEDLINE | ID: mdl-30624194

ABSTRACT

CONTEXT: Cannabidiol (CBD) is one of many cannabinoid compounds found in cannabis. It does not appear to alter consciousness or trigger a "high." A recent surge in scientific publications has found preclinical and clinical evidence documenting value for CBD in some neuropsychiatric disorders, including epilepsy, anxiety, and schizophrenia. Evidence points toward a calming effect for CBD in the central nervous system. Interest in CBD as a treatment of a wide range of disorders has exploded, yet few clinical studies of CBD exist in the psychiatric literature. OBJECTIVE: To determine whether CBD helps improve sleep and/or anxiety in a clinical population. DESIGN: A large retrospective case series at a psychiatric clinic involving clinical application of CBD for anxiety and sleep complaints as an adjunct to usual treatment. The retrospective chart review included monthly documentation of anxiety and sleep quality in 103 adult patients. MAIN OUTCOME MEASURES: Sleep and anxiety scores, using validated instruments, at baseline and after CBD treatment. RESULTS: The final sample consisted of 72 adults presenting with primary concerns of anxiety (n = 47) or poor sleep (n = 25). Anxiety scores decreased within the first month in 57 patients (79.2%) and remained decreased during the study duration. Sleep scores improved within the first month in 48 patients (66.7%) but fluctuated over time. In this chart review, CBD was well tolerated in all but 3 patients. CONCLUSION: Cannabidiol may hold benefit for anxiety-related disorders. Controlled clinical studies are needed.


Subject(s)
Anxiety/drug therapy , Cannabidiol/therapeutic use , Sleep Initiation and Maintenance Disorders/drug therapy , Adolescent , Adult , Aged , Cannabidiol/adverse effects , Female , Humans , Male , Middle Aged , Retrospective Studies , Sleep/drug effects , Young Adult
20.
J Sci Med Sport ; 22(1): 70-75, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30031747

ABSTRACT

OBJECTIVES: Rural Australian adults are consistently identified as insufficiently active, likely due to challenges implementing community-based physical activity programs in rural settings. On-line strategies to promote physical activity may be particularly effective in rural settings where isolation and scarcity of qualified support are potential barriers. The Rural Environments and Community Health (REACH) study evaluated the effectiveness of an online-delivered walking intervention among South Australian rural adults. DESIGN: Randomised controlled study design. METHODS: A twelve-week intervention, with six- and twelve-month follow-up, was conducted. Participants (n=171; 50.6±12.5years), recruited through flyers, local newspapers and radio, were randomised to comparison or intervention groups and received a pedometer. The intervention group received access to the REACH website and personalised step goals based on ratings of perceived exertion and daily affect. The comparison group received a paper diary and generic step goals. Outcome measures were accelerometry-assessed sedentary, light (LPA) and moderate-to-vigorous (MVPA) physical activity. Linear mixed models assessed changes over the intervention and follow-ups. RESULTS: Sedentary time decreased, and LPA and MVPA increased in both groups across the intervention (p<0.05). The intervention group demonstrated a larger increase in LPA at six-month follow-up relative to comparison (p<0.05). Both groups decreased sedentary time, overall and in bouts ≥30min, between baseline and twelve-month follow-up (p<0.05). From baseline to twelve-month follow-up, MVPA (total min and bouts ≥10min) declined more in the comparison group than the intervention group (p<0.05). CONCLUSION: While increased physical activity and decreased sedentary time were observed in both groups during the intervention period, maintenance was only observed for LPA at six-month follow-up in the intervention group. By twelve-month follow-up, post-intervention improvements had largely disappeared, suggesting that additional research is needed to identify ways to improve long-term adherence.


Subject(s)
Exercise , Health Promotion/methods , Internet , Walking , Accelerometry , Adult , Australia , Female , Fitness Trackers , Humans , Male , Middle Aged , Rural Population
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