Publications by authors named "J Michael Oakes"

338 Publications

Structural and functional remodeling of the female Apoe mouse aorta due to chronic cigarette smoke exposure.

Am J Physiol Heart Circ Physiol 2021 Apr 9. Epub 2021 Apr 9.

Department of Bioengineering. Northeastern University, Boston, MA, USA.

Despite a decline in popularity over the last several decades, cigarette smoking remains a leading cause of cardiovascular morbidity and mortality. Yet, the effects of cigarette smoking on vascular structure and function are largely unknown. To evaluate changes in the mechanical properties of the aorta that occur with chronic smoking, we exposed female Apolipoprotein E-deficient mice to mainstream cigarette smoke daily for 24 weeks, with room air as control. By the time of sacrifice, cigarette-exposed mice had lower body mass, but experienced larger systolic/diastolic blood pressure when compared to controls. Smoking was associated with significant wall thickening, reduced axial stretch, and circumferential material softening of the aorta. While this contributed to maintaining intrinsic tissue stiffness at control levels despite larger pressure loads, the structural stiffness became significantly larger. Furthermore, the aorta from cigarette-exposed mice exhibited decreased ability to store elastic energy and augment diastolic blood flow. Histological analysis revealed a region-dependent increase in the cross-sectional area due to smoking. Increased smooth muscle and extracellular matrix content led to medial thickening in the ascending aorta, while collagen deposition increased the thickness of the descending thoracic and abdominal aorta. Atherosclerotic lesions were larger in exposed vessels and featured a necrotic core overlaid by a thinned fibrous cap and macrophage infiltration, consistent with a vulnerable phenotype. Collectively, our data indicate that cigarette smoking decreases the mechanical functionality of the aorta, inflicts morphometric alterations to distinct segments of the aorta, and accelerates the progression of atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpheart.00893.2020DOI Listing
April 2021

Perceptions of a food benefit program that includes financial incentives for the purchase of fruits and vegetables and restrictions on the purchase of foods high in added sugar.

Public Health Nutr 2021 Mar 12:1-24. Epub 2021 Mar 12.

University of Minnesota Twin cities, School of Public Health, Division of Epidemiology and Community Health.

Objective: To report perspectives of participants in a food benefit program that includes FAS restrictions and FAS restrictions paired with F/V incentives.

Design: Randomized experimental trial in which participant perspectives were an exploratory study outcome.

Setting: Participants were randomized into one of three SNAP-like food benefit program groups - (1) Restriction: not allowed to buy FAS with benefits; (2) Restriction paired with incentive: not allowed to buy FAS with benefits and 30% financial incentive on eligible F/V purchased using benefits; or (3) Control: Same food purchasing rules as SNAP. Participants were asked questions to assess program satisfaction.

Participants: Adults in the Minneapolis-St. Paul, MN metropolitan area, eligible for but not currently participating in SNAP who completed baseline and follow-up study measures (n=254).

Results: Among remaining households in each group, most found the program helpful in buying nutritious foods (88.2%-95.7%) and were satisfied with the program (89.1%-93.0%). Sensitivity analysis results indicate that reported helpfulness and satisfaction with the program may in some instances be lower among the Restriction and the Restrictions paired with Incentive groups in comparison to the control group.

Conclusions: A food benefit program that includes restriction on purchase of FAS or restriction paired with a financial incentive for F/V purchases may be acceptable to most SNAP-eligible households with children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1368980021001051DOI Listing
March 2021

Cerebral Palsy Research Network Clinical Registry: Methodology and Baseline Report.

Arch Rehabil Res Clin Transl 2020 Sep 19;2(3):100054. Epub 2020 Apr 19.

Department of Pediatrics, Nationwide Children's Hospital, Ohio State University, Columbus, Ohio.

Objective: To apply practice-based evidence to clinical management of cerebral palsy (CP). The process of establishing purpose, structure, logistics, and elements of a multi-institutional registry and the baseline characteristics of initial enrollees are reported.

Design: A consensus-building process among consumers, clinicians, and researchers used a participatory action process.

Setting: Community, hospitals, and universities.

Participants: More than 100 clinicians, researchers, and consumers and more than 1858 enrollees in the registry.

Main Outcome Measures: Not applicable.

Results: Consensus was that the purpose of registry was to (1) quantify practice variation, (2) facilitate quality improvement (QI), and (3) perform comparative effectiveness research (CER). Collecting data during routine clinical care using the electronic medical record was determined to be a sustainable plan for data acquisition and management. Clinicians from multiple disciplines defined salient characteristics of individuals and interventions for the registry elements. The registry was central to the clinical research network, and a leadership structure was created. A leading electronic health record platform adopted the registry elements. Twenty-four sites have initiated the data collection process and agreed to export data to the registry. Currently 12 are collecting data. Number of enrollees and characteristics were similar to other population registers.

Conclusions: This is the first multi-institutional CP registry that contains the patient and treatment characteristics needed for QI and CER. The Cerebral Palsy Research Network registry elements are implemented in a versatile electronic platform and minimize burden to clinicians. The resultant registry is available for any institution to participate and is growing rapidly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arrct.2020.100054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853390PMC
September 2020

Safety and Outcomes of Prolonged Usual Care Prone Position Mechanical Ventilation to Treat Acute Coronavirus Disease 2019 Hypoxemic Respiratory Failure.

Crit Care Med 2021 03;49(3):490-502

Department of Medicine, Pulmonary and Critical Care Medicine, Denver Health Medical Center, Denver, CO.

Objectives: Prone position ventilation is a potentially life-saving ancillary intervention but is not widely adopted for coronavirus disease 2019 or acute respiratory distress syndrome from other causes. Implementation of lung-protective ventilation including prone positioning for coronavirus disease 2019 acute respiratory distress syndrome is limited by isolation precautions and personal protective equipment scarcity. We sought to determine the safety and associated clinical outcomes for coronavirus disease 2019 acute respiratory distress syndrome treated with prolonged prone position ventilation without daily repositioning.

Design: Retrospective single-center study.

Setting: Community academic medical ICU.

Patients: Sequential mechanically ventilated patients with coronavirus disease 2019 acute respiratory distress syndrome.

Interventions: Lung-protective ventilation and prolonged protocolized prone position ventilation without daily supine repositioning. Supine repositioning was performed only when Fio2 less than 60% with positive end-expiratory pressure less than 10 cm H2O for greater than or equal to 4 hours.

Measurements And Main Results: Primary safety outcome: proportion with pressure wounds by Grades (0-4). Secondary outcomes: hospital survival, length of stay, rates of facial and limb edema, hospital-acquired infections, device displacement, and measures of lung mechanics and oxygenation. Eighty-seven coronavirus disease 2019 patients were mechanically ventilated. Sixty-one were treated with prone position ventilation, whereas 26 did not meet criteria. Forty-two survived (68.9%). Median (interquartile range) time from intubation to prone position ventilation was 0.28 d (0.11-0.80 d). Total prone position ventilation duration was 4.87 d (2.08-9.97 d). Prone position ventilation was applied for 30.3% (18.2-42.2%) of the first 28 days. Pao2:Fio2 diverged significantly by day 3 between survivors 147 (108-164) and nonsurvivors 107 (85-146), mean difference -9.632 (95% CI, -48.3 to 0.0; p = 0·05). Age, driving pressure, day 1, and day 3 Pao2:Fio2 were predictive of time to death. Thirty-eight (71.7%) developed ventral pressure wounds that were associated with prone position ventilation duration and day 3 Sequential Organ Failure Assessment. Limb weakness occurred in 58 (95.1%) with brachial plexus palsies in five (8.2%). Hospital-acquired infections other than central line-associated blood stream infections were infrequent.

Conclusions: Prolonged prone position ventilation was feasible and relatively safe with implications for wider adoption in treating critically ill coronavirus disease 2019 patients and acute respiratory distress syndrome of other etiologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000004818DOI Listing
March 2021

Neighborhood Socioeconomic Status and Identification of Patients With CKD Using Electronic Health Records.

Am J Kidney Dis 2020 Dec 16. Epub 2020 Dec 16.

- Division of Renal Diseases and Hypertension, University of Minnesota, Minneapolis, MN.

Rational & Objective: Screening for chronic kidney disease (CKD) is recommended for patients with diabetes and hypertension as stated by their respective societies. However, CKD, a silent disease usually detected at later stages, is associated with low socioeconomic status (SES). We assessed whether adding census tract SES status to the standard screening approach improves our ability to identify patients with CKD.

Study Design: Screening test analysis SETTINGS & PARTICIPANTS: Electronic health records (EHR) of 256,162 patients seen at a healthcare system in the 7 county Minneapolis/St.Paul area and linked census tract data.

Exposures: First quartile of census tract SES [median value of owner occupied housing units (<$165,200), average household income (<$35,935), percentage of residents >25 years with a Bachelor's degree or more (<20.4%], hypertension and diabetes OUTCOMES: CKD [eGFR< 60/mL/min/1.73m or UACR>30mg/g or UPCR >150mg/g or UA>30mg/g] ANALYTIC APPROACH: Sensitivity, specificity, and number needed to screen (NNS) to detect CKD if we screen patients who have hypertension and/or diabetes and/or who live in low SES tracts (belonging to the first quartile of any of the three measures of tract SES) vs. standard approach.

Results: CKD was prevalent in 13% of our cohort. Sensitivity, specificity, and NNS of detecting CKD after adding tract SES to the screening approach was 67% [95%CI: 66.2, 67.2] , 61% [95%CI: 61.1, 61.5] and 5, respectively. With the standard approach, sensitivity of detecting CKD was 60% [95% CI: 59.4, 60.4], specificity was 73% [95%CI: 72.4, 72.7] and NNS was 4, respectively.

Limitations: One healthcare system and selection bias CONCLUSIONS: Leveraging patients' addresses from the EHR and adding tract level SES to standard screening approach modestly increases the sensitivity of detecting patients with CKD at a cost of decreased specificity. Identifying further factors that improve CKD detection at an early stage are needed to slow the progression of CKD and prevent cardiovascular complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.ajkd.2020.10.019DOI Listing
December 2020

Maternal Microdeletion at the ICR in Mice Increases Offspring Susceptibility to Environmental Perturbation.

Epigenet Insights 2020 2;13:2516865720970575. Epub 2020 Dec 2.

Department of Nutrition, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Deficiency of methyl donor nutrients folate, choline, and methionine (methyl deficiency) during gestation can impair fetal development and perturb DNA methylation. Here, we assessed genetic susceptibility to methyl deficiency by comparing effects in wildtype C57BL/6J (B6) mice to mutant mice carrying a 1.3 kb deletion at the Imprinting Control Region (ICR) (). The mutation mimics microdeletions observed in Beckwith-Wiedemann syndrome (BWS) patients, who exhibit epimutations in that cause loss of imprinting and fetal overgrowth. Dams were treated during pregnancy with 1 of 4 methyl sufficient (MS) or methyl deficient (MD) diets, with or without the antibiotic commonly used to deplete folate producing gut microbes. As expected, after ~9 weeks of treatment, dams in MD and MD + antibiotic groups exhibited substantially reduced plasma folate concentrations. mutant lines were more susceptible to adverse pregnancy outcomes caused by methyl deficiency (reduced birth rate and increased pup lethality) and antibiotic (decreased litter size and litter survival). Surprisingly, pup growth/development was only minimally affected by methyl deficiency, while antibiotic treatment caused inverse effects on B6 and lines. B6 pups treated with antibiotic exhibited increased neonatal and weanling bodyweight, while both wildtype and mutant pups of heterozygous dams exhibited decreased neonatal bodyweight that persisted into adulthood. Interestingly, only antibiotic-treated pups carrying the mutation exhibited altered DNA methylation at the ICR, suggesting ICR epimutation was not sufficient to explain the altered phenotypes. These findings demonstrate that genetic mutation of the ICR increases offspring susceptibility to developmental perturbation in the methyl deficiency model, maternal and pup genotype play an essential role, and antibiotic treatment in the model also plays a key independent role.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2516865720970575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716063PMC
December 2020

Sewing and Inuit women's health in the Canadian Arctic.

Soc Sci Med 2020 11 16;265:113523. Epub 2020 Nov 16.

Priestley International Centre for Climate, University of Leeds, Woodhouse, Leeds, LS2 9JT, United Kingdom.

Traditional Inuit cultural values and practices are integral to an Inuit understanding of health. We examine the role of sewing in Inuit women's health in the Canadian Arctic in a case study of Ulukhaktok, Northwest Territories, Canada. An analysis of data collected using semi-structured interviews with 30 Inuit women reveals that sewing contributes to participant's health and the collective health of the community in several ways including: pride and sense of accomplishment; cultural identity; relaxation, decompression, and socialization; and spirituality and healing. As a cultural practice, sewing is about older generations teaching younger generations about their identity, who they are and where they come from. For some participants, sewing is a way through which they express their culture. Sewing brings people together at a time when social isolation is becoming more apparent, and gives women the chance to learn vital, tangible skills that continue to have social, economic, and cultural importance. Sewing is also a form of healing that helps women ease their minds and focus on a challenging and productive task that brings them satisfaction, self-worth, and value. We conclude that sewing is important for cultural continuity, enabling Inuit to both practice and carryon their culture, and contributing positively to individual and the collective health of the community.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.socscimed.2020.113523DOI Listing
November 2020

Within- and Between-Household Variation in Food Expenditures Among Low-Income Households Using a Novel Simple Annotated Receipt Method.

Front Nutr 2020 22;7:582999. Epub 2020 Oct 22.

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, United States.

Household food purchasing behavior has gained interest as an intervention to improve nutrition and nutrition-associated outcomes. However, evaluating food expenditures is challenging in epidemiological studies. Assessment methods that are both valid and feasible for use among diverse, low-income populations are needed. We therefore developed a novel simple annotated receipt method to assess household food purchasing. First, we describe and evaluate the extent to which the method captures food purchasing information. We then evaluate within- and between-household variation in weekly food purchasing to determine sample sizes and the number of weeks of data needed to measure household food purchasing with adequate precision. Four weeks of food purchase receipt data were collected from 260 low-income households in the Minneapolis-St. Paul metropolitan area. The proportion of receipt line items that could not be coded into one of 11 food categories (unidentified) was calculated, and a zero-inflated negative binomial regression was used to evaluate the association between unidentified receipt items and participant characteristics and store type. Within- and between-household coefficients of variation were calculated for total food expenditures and several food categories. A low proportion of receipt line items (1.6%) could not be coded into a food category and the incidence of unidentified items did not appreciably vary by participant characteristics. Weekly expenditures on foods high in added sugar had higher within- and between-household coefficients of variation than weekly fruit and vegetable expenditures. To estimate mean weekly food expenditures within 20% of the group's usual ("true") expenditures, 72 households were required. Nine weeks of data were required to achieve an = 0.90 between observed and usual weekly food expenditures. The simple annotated receipt method may be a feasible tool for use in assessing food expenditures of low-income, diverse populations. Within- and between-household coefficients of variation suggest that the number of weeks of data or group sizes required to precisely estimate usual household expenditures is higher for foods high in added sugar compared to fruits and vegetables.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnut.2020.582999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642585PMC
October 2020

Efficacy of the 'Stand and Move at Work' multicomponent workplace intervention to reduce sedentary time and improve cardiometabolic risk: a group randomized clinical trial.

Int J Behav Nutr Phys Act 2020 10 27;17(1):133. Epub 2020 Oct 27.

Arizona State University, College of Health Solutions, 500 North 3rd Street, Phoenix, AZ, 85004, USA.

Background: Sedentary time is associated with chronic disease and premature mortality. We tested a multilevel workplace intervention with and without sit-stand workstations to reduce sedentary time and lower cardiometabolic risk.

Methods: Stand and Move at Work was a group (cluster) randomized trial conducted between January 2016 and December 2017 among full-time employees; ≥18 years; and in academic, industry/healthcare, and government worksites in Phoenix, Arizona and Minneapolis/St. Paul, Minnesota, USA. Eligible worksites were randomized to (a) MOVE+, a multilevel intervention targeting reduction in sedentary time and increases in light physical activity (LPA); or (b) STAND+, the MOVE+ intervention along with sit-stand workstations to allow employees to sit or stand while working. The primary endpoints were objectively-measured workplace sitting and LPA at 12 months. The secondary endpoint was a clustered cardiometabolic risk score (blood pressure, glucose, insulin, triglycerides, and HDL-cholesterol) at 12 months.

Results: Worksites (N = 24; academic [n = 8], industry/healthcare [n = 8], and government [n = 8] sectors) and employees (N = 630; 27 ± 8 per worksite; 45 ± 11 years of age, 74% female) were enrolled. All worksites were retained and 487 participants completed the intervention and provided data for the primary endpoint. The adjusted between arm difference in sitting at 12 months was - 59.2 (CI: - 74.6,-43.8) min per 8 h workday, favoring STAND+, and in LPA at 12 months was + 2.2 (- 0.9,5.4) min per 8 h workday. Change in the clustered metabolic risk score was small and not statistically significant, but favored STAND+. In an exploratory subgroup of 95 participants with prediabetes or diabetes, the effect sizes were larger and clinically meaningful, all favoring STAND+, including blood glucose, triglycerides, systolic blood pressure, glycated hemoglobin, LDL-cholesterol, body weight, and body fat.

Conclusions: Multilevel workplace interventions that include the use of sit-stand workstations are effective for large reductions in sitting time over 12 months. Among those with prediabetes or diabetes, clinical improvements in cardiometabolic risk factors and body weight may be realized.

Trial Registration: ClinicalTrials.gov Identifier: NCT02566317 . Registered 2 October 2015, first participant enrolled 11 January 2016.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12966-020-01033-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592578PMC
October 2020

A shift in the pool of retained microphytobenthos nitrogen under enhanced nutrient availability.

Water Res 2020 Dec 19;187:116438. Epub 2020 Sep 19.

Centre for Coastal Biogeochemistry, Southern Cross University, PO Box 157, Lismore, NSW 2480, Australia.

Sediment microbial communities are an important sink for both organic and inorganic nitrogen (N), with microphytobenthos (MPB) biomass making the largest contribution to short-term N-assimilation and retention. Coastal waters are increasingly subject to anthropogenic nutrient enrichment, but the effect of nutrient enrichment on microbial assimilation, processing, and fate of MPB-derived N (MPB-N) remains poorly characterised. In this study, an MPB-dominated microbial community was labeled in situ with a pulse of NH-N. Laboratory core incubations of this labeled sediment under increasing nutrient concentrations (NH and PO: ambient, 2 × ambient, 5 × ambient, and 10 × ambient) were used to investigate changes in the processing and flux pathways of the N-labeled MPB-N across 10.5 d under nutrient enrichment. Short-term retention of MPB-N by MPB was stimulated by nutrient addition, with higher N in MPB in the nutrient amended treatments (71-93%) than in the ambient treatment (38%) at 0.5 d After 10.5 d, the nutrient amended treatments had increased turnover of MPB-N out of MPB biomass into an uncharacterised pool of sediment ON (45-75%). Increased turnover of MPB-N likely resulted from decreased recycling of MPB-N between MPB and heterotrophic bacteria as inorganic nutrients were preferentially used as an N source and remineralisation of sediment ON decreased. Decreased breakdown of sediment ON reduced the efflux of MPB-N via DON in the amended (3.9-5.2%) versus the ambient treatment (10.9%). Exports of MPB-N to the water column were relatively small, accounting for a maximum of 14% of N exported from the sediment, and were predominantly exported DON and N (denitrification). Overall, there was considerable retention of MPB-N over 10.5 d, but increased nutrient loading shifted N from MPB biomass into other sediment ON.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.watres.2020.116438DOI Listing
December 2020

Lung-derived HMGB1 is detrimental for vascular remodeling of metabolically imbalanced arterial macrophages.

Nat Commun 2020 08 27;11(1):4311. Epub 2020 Aug 27.

Division of Vascular Surgery, Department of Surgery, New York University Langone Health, New York, NY, USA.

Pulmonary disease increases the risk of developing abdominal aortic aneurysms (AAA). However, the mechanism underlying the pathological dialogue between the lungs and aorta is undefined. Here, we find that inflicting acute lung injury (ALI) to mice doubles their incidence of AAA and accelerates macrophage-driven proteolytic damage of the aortic wall. ALI-induced HMGB1 leaks and is captured by arterial macrophages thereby altering their mitochondrial metabolism through RIPK3. RIPK3 promotes mitochondrial fission leading to elevated oxidative stress via DRP1. This triggers MMP12 to lyse arterial matrix, thereby stimulating AAA. Administration of recombinant HMGB1 to WT, but not Ripk3 mice, recapitulates ALI-induced proteolytic collapse of arterial architecture. Deletion of RIPK3 in myeloid cells, DRP1 or MMP12 suppression in ALI-inflicted mice repress arterial stress and brake MMP12 release by transmural macrophages thereby maintaining a strengthened arterial framework refractory to AAA. Our results establish an inter-organ circuitry that alerts arterial macrophages to regulate vascular remodeling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-18088-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453029PMC
August 2020

Quantitative Method for Comparative Assessment of Particle Removal Efficiency of Fabric Masks as Alternatives to Standard Surgical Masks for PPE.

Matter 2020 Sep 9;3(3):950-962. Epub 2020 Jul 9.

Departments of Civil and Environmental Engineering and Marine and Environmental Science, Northeastern University, Boston, MA 02115, USA.

In response to the COVID-19 pandemic, cloth masks are being used to control the spread of virus, but the efficacy of these loose-fitting masks is not well known. Here, tools and methods typically used to assess tight-fitting respirators were modified to quantify the efficacy of community-produced and commercially produced fabric masks as personal protective equipment. Two particle counters concurrently sample ambient air and air inside the masks; mask performance is evaluated by mean particle removal efficiency and statistical variability when worn as designed and with a nylon overlayer, to independently assess fit and material. Worn as designed, both commercial surgical masks and cloth masks had widely varying effectiveness (53%-75% and 28%-91% particle removal efficiency, respectively). Most surgical-style masks improved with the nylon overlayer, indicating poor fit. This rapid testing method uses widely available hardware, requires only a few calculations from collected data, and provides both a holistic and aspect-wise evaluation of mask performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.matt.2020.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346791PMC
September 2020

11β-Hydroxylase loss disrupts steroidogenesis and reproductive function in zebrafish.

J Endocrinol 2020 11;247(2):197-212

Department of Oncology & Metabolism, School of Medicine, University of Sheffield, Sheffield, UK.

The roles of androgens in male reproductive development and function in zebrafish are poorly understood. To investigate this topic, we employed CRISPR/Cas9 to generate cyp11c1 (11β-hydroxylase) mutant zebrafish lines. Our study confirms recently published findings from a different cyp11c1-/- mutant zebrafish line, and also reports novel aspects of the phenotype caused by loss of Cyp11c1 function. We report that Cyp11c1-deficient zebrafish display predominantly female secondary sex characteristics, but may possess either ovaries or testes. Moreover, we observed that cyp11c1-/- mutant male zebrafish are profoundly androgen- and cortisol-deficient. These results provide further evidence that androgens are dispensable for testis formation in zebrafish, as has been demonstrated previously in androgen-deficient and androgen-resistant zebrafish. Herein, we show that the testes of cyp11c1-/- mutant zebrafish exhibit a disorganised tubular structure; and for the first time demonstrate that the spermatic ducts, which connect the testes to the urogenital orifice, are severely hypoplastic in androgen-deficient zebrafish. Furthermore, we show that spermatogenesis and characteristic breeding behaviours are impaired in cyp11c1-/- mutant zebrafish. Expression of nanos2, a type A spermatogonia marker, was significantly increased in the testes of Cyp11c1-deficient zebrafish, whereas expression of markers for later stages of spermatogenesis was significantly decreased. These observations indicate that in zebrafish, production of type A spermatogonia is androgen-independent, but differentiation of type A spermatogonia is an androgen-dependent process. Overall, our results demonstrate that whilst androgens are not required for testis formation, they play important roles in determining secondary sexual characteristics, proper organisation of seminiferous tubules, and differentiation of male germ cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/JOE-20-0160DOI Listing
November 2020

Shining Light on Priming in Euphotic Sediments: Nutrient Enrichment Stimulates Export of Stored Organic Matter.

Environ Sci Technol 2020 09 26;54(18):11165-11172. Epub 2020 Aug 26.

Centre for Coastal Biogeochemistry, School of Environment, Science and Engineering, Southern Cross University, P.O. Box 157, Lismore, NSW 2480, Australia.

Estuarine sediments are important sites for the interception, processing, and retention of organic matter, prior to its export to the coastal oceans. Stimulated microbial co-metabolism (priming) potentially increases export of refractory organic matter through increased production of hydrolytic enzymes. Using the microphytobenthos community to directly introduce a pulse of labile carbon into sediment, we traced a priming effect and assessed the decomposition and export of preexisting organic matter. We show enhanced efflux of preexisting carbon from intertidal sediments enriched with water column nutrients. Nutrient enrichment increased production of labile microphytobenthos carbon, which stimulated degradation of previously unavailable organic matter and led to increased liberation of "old" (6855 ± 120 years BP) refractory carbon as dissolved organic carbon (DOC). These enhanced DOC effluxes occurred at a scale that decreases estimates for global organic carbon burial in coastal systems and should be considered as an impact of eutrophication on estuarine carbon budgets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.0c01914DOI Listing
September 2020

Preliminary Evidence of the Role of Medial Prefrontal Cortex in Self-Enhancement: A Transcranial Magnetic Stimulation Study.

Brain Sci 2020 Aug 8;10(8). Epub 2020 Aug 8.

Cognitive Neuroimaging Laboratory, 207 Science Hall, Montclair State University, Upper Montclair, NJ 07043, USA.

Humans employ a number of strategies to improve their position in their given social hierarchy. Overclaiming involves presenting oneself as having more knowledge than one actually possesses, and it is typically invoked to increase one's social standing. If increased expectations to possess knowledge is a perceived social pressure, such expectations should increase bouts of overclaiming. As the medial prefrontal cortex (MPFC) is sensitive to social pressure and disruption of the MPFC leads to decreases in overclaiming, we predicted that transcranial magnetic stimulation (TMS) applied to the MPFC would reduce overclaiming and the effects would be enhanced in the presence of social pressure. Twelve participants were given a test in which half of the words were real and half were fake, and they were asked how well they knew each word. They were not told that any of the words were fake. Half of the participants were exposed to social pressure while the other half were not. Following TMS delivered to the MPFC, overclaiming rates decreased, specifically under conditions of high social pressure. Medial PFC TMS did not influence real word responses and real words did not interact with the MPFC and social pressure. These preliminary findings support the significant role the MPFC plays in social cognition and the importance of the MPFC in mediating socially meaningful situations. We suggest the role of the MPFC as being highly influenced by the premium placed on social manipulation in human evolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/brainsci10080535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464708PMC
August 2020

Preliminary Evidence of the Role of Medial Prefrontal Cortex in Self-Enhancement: A Transcranial Magnetic Stimulation Study.

Brain Sci 2020 Aug 8;10(8). Epub 2020 Aug 8.

Cognitive Neuroimaging Laboratory, 207 Science Hall, Montclair State University, Upper Montclair, NJ 07043, USA.

Humans employ a number of strategies to improve their position in their given social hierarchy. Overclaiming involves presenting oneself as having more knowledge than one actually possesses, and it is typically invoked to increase one's social standing. If increased expectations to possess knowledge is a perceived social pressure, such expectations should increase bouts of overclaiming. As the medial prefrontal cortex (MPFC) is sensitive to social pressure and disruption of the MPFC leads to decreases in overclaiming, we predicted that transcranial magnetic stimulation (TMS) applied to the MPFC would reduce overclaiming and the effects would be enhanced in the presence of social pressure. Twelve participants were given a test in which half of the words were real and half were fake, and they were asked how well they knew each word. They were not told that any of the words were fake. Half of the participants were exposed to social pressure while the other half were not. Following TMS delivered to the MPFC, overclaiming rates decreased, specifically under conditions of high social pressure. Medial PFC TMS did not influence real word responses and real words did not interact with the MPFC and social pressure. These preliminary findings support the significant role the MPFC plays in social cognition and the importance of the MPFC in mediating socially meaningful situations. We suggest the role of the MPFC as being highly influenced by the premium placed on social manipulation in human evolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/brainsci10080535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464708PMC
August 2020

Integrated Image-Based Computational Fluid Dynamics Modeling Software as an Instructional Tool.

J Biomech Eng 2020 Jun 12. Epub 2020 Jun 12.

Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.

Computational modeling of cardiovascular flows is becoming increasingly important in a range of biomedical applications, and understanding the fundamentals of computational modeling is important for engineering students. In addition to their purpose as research tools, integrated image-based computational fluid dynamics platforms can be used to teach the fundamental principles involved in computational modeling and generate interest in studying cardiovascular disease. We report the results of a study performed at five institutions designed to investigate the effectiveness of an integrated modeling platform as an instructional tool and describe "best practices" for using an integrated modeling platform in the classroom. Use of an integrated modeling platform as an instructional tool in nontraditional educational settings (workshops, study abroad programs, in outreach) is also discussed. Results of the study show statistically significant improvements in understanding after using the integrated modeling platform, suggesting such platforms can be effective tools for teaching fundamental cardiovascular computational modeling principles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1115/1.4047479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580653PMC
June 2020

Acute neuroradiological, behavioral, and physiological effects of nose-only exposure to vaporized cannabis in C57BL/6 mice.

Inhal Toxicol 2020 04 1;32(5):200-217. Epub 2020 Jun 1.

Department of Bioengineering, Northeastern University, Boston, MA, USA.

The rapid increase of cannabis consumption reinforces the need to elucidate the health hazards of this practice. The presence of fine particulate matter in cannabis smoke and vapor poses a major concern, as it may contribute to cardiopulmonary disease. To facilitate the assessment of risks associated with cannabis inhalation, we developed and characterized a method for exposing mice to cannabis in a way that mimics the delivery of the drug to the airways of smokers. Cannabis (10.3% THC, 0.05% CBD) was vaporized to generate aerosols with a reproducible particle profile. Aerosols were acutely delivered to male, adult C57BL/6 mice via a nose-only exposure system. Serum THC levels were measured for increasing cannabis doses. Blood pressure and heart rate were recorded at baseline and following exposure. Behavioral response to cannabis inhalation in the open field was documented. Awake neurological activity upon cannabis exposure was monitored using BOLD fMRI. Cannabis aerosols contained particles with count median diameter of 243 ± 39 nm and geometric standard deviation of 1.56 ± 0.06. Blood serum THC levels increased linearly with aerosolized mass and peaked at 136 ± 5 ng/mL. Cannabis inhalation decreased heart rate and blood pressure but promoted anxiety-like behavior. Observed differences in BOLD activation volumes linked cannabis to increased awareness to sensory stimuli and reduced behavioral arousal. Quantified physiological, behavioral, and neurological responses served as validation for our mouse model of cannabis inhalation. Animal models of aerosol exposure will be instrumental for uncovering the health outcomes of chronic cannabis use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08958378.2020.1767237DOI Listing
April 2020

A six-step brief intervention to reduce distress and increase treatment readiness in problem gamblers.

Australas Psychiatry 2020 08 19;28(4):418-422. Epub 2020 May 19.

Monash Addiction Research Centre, Eastern Health Clinical School, Monash University, Australia.

Objective: The majority of people with gambling problems contact helplines when they are in crisis, hampering their capacity to explore suitable treatment options. To date, there has been limited research identifying the best way to support individuals to reduce distress and maximise further treatment-seeking. In this paper, we describe the development and piloting of the resulting six-step brief intervention.

Method: A six-step brief intervention was developed based on a literature review of existing interventions for crisis management, semi-structured interviews with 19 participants comprising gambling and crisis support counsellors and consumers, as well as experts in the addiction field.

Results: The resulting six-step brief-intervention focusses on (1) acknowledging and measuring distress; (2) normalising and reducing distress; (3) optimising motivation for change; (4) providing a sense of hope; (5) re-measuring distress and, if reduced; (6) exploring options for treatment and support.

Conclusion: Whilst developed primarily for helpline counsellors, the intervention has potential application for health practitioners working across telephone, online and face-to-face services. Further research is required to determine its effectiveness in improving treatment engagement amongst people with gambling problems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1039856220901471DOI Listing
August 2020

Particle transport and deposition correlation with near-wall flow characteristic under inspiratory airflow in lung airways.

Comput Biol Med 2020 05 14;120:103703. Epub 2020 Mar 14.

Department of Mechanical Engineering, Northern Arizona University, Flagstaff, AZ, United States. Electronic address:

Exposure of lung airways to detrimental suspended aerosols in the environment increases the vulnerability of the respiratory and cardiovascular systems. In addition, recent developments in therapeutic inhalation devices magnify the importance of particle transport. In this manuscript, particle transport and deposition patterns in the upper tracheobronchial (TB) tree were studied where the inertial forces are considerable for microparticles. Wall shear stress divergence (WSSdiv) is proposed as a wall-based parameter that can predict particle deposition patterns. WSSdiv is proportional to near-wall normal velocity and can quantify the strength of flow towards and away from the wall. Computational fluid dynamics (CFD) simulations were performed to quantify airflow velocity and WSS vectors for steady inhalation in one case-control and unsteady inhalation in six subject-specific airway trees. Turbulent flow simulation was performed for the steady case using large eddy simulation to study the effect of turbulence. Magnetic resonance velocimetry (MRV) measurements were used to validate the case-control CFD simulation. Inertial particle transport was modeled by solving the Maxey-Riley equation in a Lagrangian framework. Deposition percentage (DP) was quantified for the case-control model over five particle sizes. DP was found to be proportional to particle size in agreement with previous studies in the literature. A normalized deposition concentration (DC) was defined to characterize localized deposition. A relatively strong correlation (Pearson value > 0.7) was found between DC and positive WSSdiv for physiologically relevant Stokes (St) numbers. Additionally, a regional analysis was performed after dividing the lungs into smaller areas. A spatial integral of positive WSSdiv over each division was shown to maintain a very strong correlation (Pearson value > 0.9) with cumulative spatial DC or regional dosimetry. The conclusions were generalized to a larger population in which two healthy and four asthmatic patients were investigated. This study shows that WSSdiv could be used to predict the qualitative surface deposition and relative regional dosimetry without the need to solve a particle transport problem.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.compbiomed.2020.103703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237327PMC
May 2020

Effects of Chronic Nicotine Inhalation on Systemic and Pulmonary Blood Pressure and Right Ventricular Remodeling in Mice.

Hypertension 2020 05 16;75(5):1305-1314. Epub 2020 Mar 16.

From the Department of Physiology (J.M.O., N.D.F., C.S.P., T.D.L., N.W.G., J.D.G., X.Y.), Louisiana State University Health Sciences Center, New Orleans.

Cigarette smoking is the single most important risk factor for the development of cardiovascular and pulmonary diseases; however, the role of nicotine in the pathogenesis of these diseases is incompletely understood. The purpose of this study was to examine the effects of chronic nicotine inhalation on the development of cardiovascular and pulmonary disease with a focus on blood pressure and cardiac remodeling. Male C57BL6/J mice were exposed to air (control) or nicotine vapor (daily, 12 hour on/12 hour off) for 8 weeks. Systemic blood pressure was recorded weekly by radio-telemetry, and cardiac remodeling was monitored by echocardiography. At the end of the 8 weeks, mice were subjected to right heart catheterization to measure right ventricular systolic pressure. Nicotine-exposed mice exhibited elevated systemic blood pressure from weeks 1 to 3, which then returned to baseline from weeks 4 to 8, indicating development of tolerance to nicotine. At 8 weeks, significantly increased right ventricular systolic pressure was detected in nicotine-exposed mice compared with the air controls. Echocardiography showed that 8-week nicotine inhalation resulted in right ventricular (RV) hypertrophy with increased RV free wall thickness and a trend of increase in RV internal diameter. In contrast, there were no significant structural or functional changes in the left ventricle following nicotine exposure. Mechanistically, we observed increased expression of angiotensin-converting enzyme and enhanced activation of mitogen-activated protein kinase pathways in the RV but not in the left ventricle. We conclude that chronic nicotine inhalation alters both systemic and pulmonary blood pressure with the latter accompanied by RV remodeling, possibly leading to progressive and persistent pulmonary hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145734PMC
May 2020

Identification of quantitative trait loci associated with nitrogen use efficiency in winter wheat.

PLoS One 2020 24;15(2):e0228775. Epub 2020 Feb 24.

School of Plant and Environmental Sciences, Virginia Tech, Blacksburg, Virginia, United States of America.

Maintaining winter wheat (Triticum aestivum L.) productivity with more efficient nitrogen (N) management will enable growers to increase profitability and reduce the negative environmental impacts associated with nitrogen loss. Wheat breeders would therefore benefit greatly from the identification and application of genetic markers associated with nitrogen use efficiency (NUE). To investigate the genetics underlying N response, two bi-parental mapping populations were developed and grown in four site-seasons under low and high N rates. The populations were derived from a cross between previously identified high NUE parents (VA05W-151 and VA09W-52) and a shared common low NUE parent, 'Yorktown.' The Yorktown × VA05W-151 population was comprised of 136 recombinant inbred lines while the Yorktown × VA09W-52 population was comprised of 138 doubled haploids. Phenotypic data was collected on parental lines and their progeny for 11 N-related traits and genotypes were sequenced using a genotyping-by-sequencing platform to detect more than 3,100 high quality single nucleotide polymorphisms in each population. A total of 130 quantitative trait loci (QTL) were detected on 20 chromosomes, six of which were associated with NUE and N-related traits in multiple testing environments. Two of the six QTL for NUE were associated with known photoperiod (Ppd-D1 on chromosome 2D) and disease resistance (FHB-4A) genes, two were reported in previous investigations, and one QTL, QNue.151-1D, was novel. The NUE QTL on 1D, 6A, 7A, and 7D had LOD scores ranging from 2.63 to 8.33 and explained up to 18.1% of the phenotypic variation. The QTL identified in this study have potential for marker-assisted breeding for NUE traits in soft red winter wheat.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228775PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039505PMC
May 2020

A randomized, placebo-controlled crossover trial of a decaffeinated energy drink shows no significant acute effect on mental energy.

Am J Clin Nutr 2020 03;111(3):719-727

Department of Health, Behavior, and Society, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.

Background: "Energy drinks" are heavily marketed to the general public, across the age spectrum. The efficacy of decaffeinated energy drinks in enhancing subjective feelings of energy (s-energy) is controversial.

Objective: The authors sought to test the efficacy of the caffeine-free version of a popular energy drink compared with a placebo drink.

Methods: This study was a randomized, double-blind, placebo-controlled, crossover trial in 223 healthy men and women aged 18-70 y with intention-to-treat and completers analysis. Participants were randomly assigned to consumption of either the decaffeinated energy drink or a placebo drink on testing day 1, and the other drink a week later. A battery of computer-based mood and cognitive tests to assess s-energy was conducted at baseline and at 0.5, 2.5, and 5 h post-ingestion. The main outcome measures were 1) mood, which was assessed by using a General Status Check Scale and the Profile of Mood States 2nd edition brief form, and 2) cognitive measures, including the N-back task (reaction time and accuracy), Reaction Time test, Flanker task (distraction avoidance), and Rapid Visual Information Processing test.

Results: No statistically significant or meaningful benefits were observed for any outcome measure, including mood and cognitive measures. Analyses of mean differences, slopes, and median differences were consistent.

Conclusions: No differences were detected across a range of mood/cognitive/behavioral/s-energy-level tests after consumption of the energy drink compared with a placebo drink in this diverse sample of adults. Thus, we found strong evidence that the energy drink is not efficacious in enhancing s-energy levels, nor any related cognitive or behavioral variables measured. In light of federal regulations, these findings suggest that labeling and marketing of some products which claim to provide these benefits may be unsubstantiated. This trial was registered at www.clinicaltrials.gov as NCT02727920.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqz343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049526PMC
March 2020

Impact of the Change Starts at Home Trial on Women's experience of intimate partner violence in Nepal.

SSM Popul Health 2020 Apr 13;10:100530. Epub 2019 Dec 13.

Department of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Minneapolis, MN, 55454, USA.

Intimate partner violence (IPV) affects 1 in 3 women worldwide. Research in low- and middle-income countries suggests that multicomponent interventions incorporating media, group work, and community mobilization may be effective at changing social norms that enable such violence. Our study aimed to evaluate the impact of a radio programme plus community engagement versus radio programming alone on the 12-month prevalence of IPV. Using a cluster randomized, repeat cross-sectional, single-blinded approach, thirty-six village communities were pair-matched within three districts in Nepal and randomly assigned to either control or intervention. Both groups were exposed to social behaviour change communication through radio programming. In addition, weekly listening and discussion groups (LDGs) were formed in intervention communities to meet and discuss radio programming over the 40-week intervention period. Participants were also exposed to other community mobilization activities such as street theatre and messaging from local leaders who were engaged in intervention programming. IPV was measured at baseline, 12 months post-baseline at program conclusion, and 28 months post-baseline using a simple random sample of 40 married women per cluster (n = approximately 1440 at each time point) along with 382 women who participated in the LDGs. Although control and intervention groups were demographically similar, baseline rates of IPV were higher in control areas. The trend in IPV for both groups was nonlinear, largely declining at midline (control condition) and rising again at endline (control and intervention conditions), possibly reflecting greater reporting due to awareness-raising activities. Significant differences between the two groups were largely absent at endline. Higher LDG attendance was associated with decreases in several forms of IPV, some of which persisted to endline. These findings suggest that intensive community engagement over longer timespans or social network measurement may be necessary to detect significant changes at the community level (NCT02942433).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ssmph.2019.100530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928358PMC
April 2020

Enhancing the utility of the problem gambling severity index in clinical settings: Identifying refined categories within the problem gambling category.

Addict Behav 2020 04 18;103:106257. Epub 2019 Dec 18.

Deakin University, Geelong, Victoria, Australia; University of Melbourne, Parkville, Victoria, Australia.

Background: The Problem Gambling Severity Index (PGSI) was intended for use in epidemiological research with gamblers across the continuum of risk. Its utility within clinical settings, where the majority of clients are problem gamblers, has been brought into question.

Aims: (1) Identify refined categories for the problem gambling category of the PGSI in help-seeking gamblers; (2) Validate these categories using the Gambling Symptom Assessment Scale (G-SAS); (3) Explore the relationship of these categories with indices of gambling and help-seeking behaviour.

Methods: Secondary data analysis of help-seeking problem gamblers from the Australian online gambling counselling/support service (Gambling Help Online [GHO]) from October 2012 to December 2015 (n = 5,881) and trial data evaluating an Australian online self-directed program for gambling (GamblingLess; n = 198). Both datasets included the PGSI, gambling frequency and expenditure. The GamblingLess dataset also included the G-SAS and help-seeking behaviour.

Results: A Latent Class Analysis, using GHO data, identified a 2-class solution. Multiple analytical methods identified a cut-off value of ≥ 19 distinguishing this 2-class solution (low problem severity: Median = 16; high problem severity: Median = 23). High problem severity gamblers had increased odds of being categorised in the higher GSAS category, greater gambling expenditure and having sought face-to-face support. The refined categories were not associated with gambling frequency, distance-based or self-directed help-seeking.

Conclusion: These findings are consistent with a stepped-care approach, whereby individuals with higher severity may be better suited to more intensive interventions and individuals with lower severity could commence with less intensive interventions and step-up to intensive interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.addbeh.2019.106257DOI Listing
April 2020

A Novel External Fixation Technique for Injuries of the Proximal Interphalangeal Joint.

Tech Hand Up Extrem Surg 2019 Dec;23(4):176-181

Department of Orthopaedic Surgery, University of Alabama, Birmingham, AL.

Digital external fixation is often used for the management of complex injuries involving the proximal interphalangeal joint, including pilon fractures of the middle phalanx base and unstable fracture-dislocations. Several dynamic "homemade" constructs have been described which utilize only K-wires and rubber bands and allow early range of motion within the construct. Although these constructs are inexpensive and their application is fairly straightforward, their designs pose a few potential problems when the construct is stressed during rehabilitation efforts. These designs utilize a blocking K-wire which relies on pin-to-pin contact to maintain reduction and creates unnecessary friction that can impede motion and result in pin loosening in bone. Furthermore, rubber band rupture can occur and destabilizes the construct. Here we present a novel technique which utilizes only K-wires and K-wire caps, provides adequate joint distraction and stabilization throughout the arc of motion, and avoids the aforementioned pitfalls of existing designs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BTH.0000000000000250DOI Listing
December 2019

The P450 side-chain cleavage enzyme Cyp11a2 facilitates steroidogenesis in zebrafish.

J Endocrinol 2020 02;244(2):309-321

Department of Oncology & Metabolism, School of Medicine, University of Sheffield, Sheffield, UK.

Cytochrome P450 side-chain cleavage enzyme, encoded by the CYP11A1 gene, catalyzes the first and rate-limiting step of steroid hormone biosynthesis. Previous morpholino-knockdown studies in zebrafish suggested cyp11a2 is a functional equivalent of human CYP11A1 and is essential for interrenal steroidogenesis in zebrafish larvae. The role of Cyp11a2 in adult zebrafish, particularly in gonadal steroidogenesis, remains elusive. To explore the role of Cyp11a2 in adults, we developed zebrafish mutant lines by creating deletions in cyp11a2 using the CRISPR/Cas9 genomic engineering approach. Homozygous cyp11a2 mutant zebrafish larvae showed an upregulation of the hypothalamic-pituitary-interrenal axis. Furthermore, these Cyp11a2-deficient zebrafish demonstrated profound glucocorticoid and androgen deficiencies. Cyp11a2 homozygotes only developed into males with feminized secondary sex characteristics. Adult cyp11a2 -/- mutant fish showed a lack of natural breeding behaviors. Histological characterization revealed disorganized testicular structure and significantly decreased numbers of mature spermatozoa. These findings are further supported by the downregulation of the expression of several pro-male genes in the testes of cyp11a2 homozygous zebrafish, including sox9a, dmrt1 and amh. Moreover, the spermatogonia markers nanos2 and piwil1 were upregulated, while the spermatocytes marker sycp3 and spermatids marker odf3b were downregulated in the testes of cyp11a2 homozygous mutants. Our expression analysis is consistent with our histological studies, suggesting that spermatogonia are the predominant cell types in the testes of cyp11a2 homozygous mutants. Our work thus demonstrates the crucial role of Cyp11a2 in interrenal and gonadal steroidogenesis in zebrafish larvae and adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/JOE-19-0384DOI Listing
February 2020

Response to the Letter to the Editor "Airflow Simulation in Pulmonary Conducting Airways" by M. Monjezi and H. Jamaati.

Ann Biomed Eng 2019 12 24;47(12):2355. Epub 2019 Oct 24.

Department of Mechanical Engineering, University of California Berkeley, Berkeley, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10439-019-02385-zDOI Listing
December 2019