Recent Research Articles from UNTHSC

Recent research articles indexed in PubMed from authors affiliated with the UNT Health Science Center.

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Updated: 2 hours 23 min ago

Lipoproteins and the Tumor Microenvironment.

Fri, 08/28/2020 - 05:05
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Lipoproteins and the Tumor Microenvironment.

Adv Exp Med Biol. 2020;1272:93-116

Authors: Dossou AS, Sabnis N, Nagarajan B, Mathew E, Fudala R, Lacko AG

Abstract
The tumor microenvironment (TME) plays a key role in enhancing the growth of malignant tumors and thus contributing to "aggressive phenotypes," supporting sustained tumor growth and metastasis. The precise interplay between the numerous components of the TME that contribute to the emergence of these aggressive phenotypes is yet to be elucidated and currently under intense investigation. The purpose of this article is to identify specific role(s) for lipoproteins as part of these processes that facilitate (or oppose) malignant growth as they interact with specific components of the TME during tumor development and treatment. Because of the scarcity of literature reports regarding the interaction of lipoproteins with the components of the tumor microenvironment, we were compelled to explore topics that were only tangentially related to this topic, to ensure that we have not missed any important concepts.

PMID: 32845504 [PubMed - in process]

Environment-Wide Association Study on Childhood Obesity in the U.S.

Wed, 08/26/2020 - 06:39
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Environment-Wide Association Study on Childhood Obesity in the U.S.

Environ Res. 2020 Aug 22;:110109

Authors: Uche UI, Suzuki S, Fulda KG, Zhou Z

Abstract
BACKGROUND: Childhood obesity is a national public health issue with increasing prevalence. It has been linked to diet, lack of physical activity, and genetic susceptibility, with more recent evidence that it could also result from environmental factors. Studies linking it to environmental factors are limited, unsystematic, incomprehensive, and inconclusive.
OBJECTIVE: To conduct an environment-wide association study (EWAS) to comprehensively investigate all the environmental factors available in a nationally representative sample of children to determine factors associated with childhood obesity.
METHODS: We utilized the 1999-2016 National Health and Nutrition Examination Survey (NHANES) datasets and included all children/adolescents (6-17 years). Obesity was measured using body mass index and waist to height ratio. A multinomial and binary logistic regression were used adjusting for age, sex, race/ethnicity, creatinine, calorie intake, physical activity, screen time, limitation to physical activities, and socioeconomic status. We then controlled for multiple hypothesis testing and validated our findings on a different cohort of children.
RESULTS: We found that metals such as beryllium (OR: 3.305 CI: 1.460-7.479) and platinum (OR: 1.346 CI: 1.107-1.636); vitamins such as gamma-tocopherol (OR: 8.297 CI: 5.683-12.114) and delta-tocopherol (OR: 1.841 CI:1.476-2.297); heterocyclic aromatic amines such as 2-Amino-9H-pyrido (2,3-b) indole (OR: 1.323 CI: 1.083-1.617) and 2-Amino-3-methyl-9H-pyriodo(2,3-b)indole (OR: 2.799 CI: 1.442-5.433); polycyclic aromatic amines such as 9- fluorene (OR: 1.509 CI: 1.230-1.851) and 4-phenanthrene (OR: 2.828 CI: 1.632-4.899); and caffeine metabolites such as 1,3,7-trimethyluric acid (OR: 1.22 CI: 1.029-1.414) and 1,3,7-trimethylxanthine (OR: 1.258 CI: 1.075-1.473) were positively and significantly associated with childhood obesity.
CONCLUSION: Following the unique concept of EWAS, certain environmental factors were associated with childhood obesity. Further studies are required to confirm these associations while investigating their mechanisms of action.

PMID: 32841636 [PubMed - as supplied by publisher]

Comparative analysis of racial differences in breast tumor microbiome.

Wed, 08/26/2020 - 06:39
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Comparative analysis of racial differences in breast tumor microbiome.

Sci Rep. 2020 Aug 24;10(1):14116

Authors: Thyagarajan S, Zhang Y, Thapa S, Allen MS, Phillips N, Chaudhary P, Kashyap MV, Vishwanatha JK

Abstract
Studies have demonstrated that environmental, host genetic, and socioeconomic factors influence the breast cancer prevalence landscape with a far-reaching influence on racial disparity to subtypes of breast cancer. To understand whether breast tissue harbors race-specific microbiota, we performed 16S rRNA gene-based sequencing of retrospective tumor and matched normal tissue adjacent to tumor (NAT) samples collected from Black non-Hispanic (BNH) and White non-Hispanic (WNH) women. Analysis of Triple Negative Breast cancer (TNBC) and Triple Positive Breast Cancer (TPBC) tissues for microbiota composition revealed significant differences in relative abundance of specific taxa at both phylum and genus levels between WNH and BNH women cohorts. Our main findings are that microbial diversity as measured by Shannon index was significantly lower in BNH TNBC tumor tissue as compared to matched NAT zone. In contrast, the WNH cohort had an inverse pattern for the Shannon index, when TNBC tumor tissue was compared to the matched NAT. Unweighted Principle Coordinates Analysis (PCoA) revealed a distinct clustering of tumor and NAT microbiota in both BNH and WNH cohorts.

PMID: 32839514 [PubMed - in process]

Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children's Oncology Group Studies P9904 and P9905.

Wed, 08/26/2020 - 06:39
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Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children's Oncology Group Studies P9904 and P9905.

Leukemia. 2020 04;34(4):1006-1016

Authors: Winick N, Martin PL, Devidas M, Shuster J, Borowitz MJ, Paul Bowman W, Larsen E, Pullen J, Carroll A, Willman C, Hunger SP, Carroll WL, Camitta BM

Abstract
The delayed intensification (DI) enhanced outcome for patients with acute lymphoblastic leukemia (ALL) treated on BFM 76/79 and CCG 105 after a prednisone-based induction. Childrens Oncology Group protocols P9904/9905 evaluated DI via a post-induction randomization for eligible National Cancer Institute (NCI) standard (SR) and high-risk (HR) patients. A second randomization compared intravenous methotrexate (IV MTX) as a 24- (1 g/m2) vs. 4-h (2 g/m2) infusion. NCI SR patients received a dexamethasone-based three-drug and NCI HR/CNS 3 SR patients a prednisone-based four-drug induction. End induction MRD (minimal residual disease) was obtained but did not impact treatment. DI improved the 10-year continuous complete remission (CCR) rate; 75.5 ± 2.5% vs. 81.8 ± 2.2% p = 0.002, whereas MTX administration did not; 4-h 80.8 ± 1.9%; 24-h 81.4 ± 1.9% (p = 0.7780). Overall survival (OS) at 10 years did not differ with DI: 91.4 ± 1.6% vs. 90.9 ± 1.7% (p = 0.25) without but was higher with the 24-h MTX infusion; 4-h 91.1 ± 1.4%; 24-h 93.9 ± 1.2% (p = 0.0209). MRD predicted outcome; 10-year CCR 87.7 ± 2.2 and 82.1 ± 2.5% when MRD was <0.01% with/without DI (p = 0.007) and 54.3 ± 8% and 44 ± 8% for patients with MRD ≥ 0.01% with/without DI (p = 0.11). DI improved CCR for patients with B-ALL with and without end induction MRD.

PMID: 31728054 [PubMed - indexed for MEDLINE]

Increased expression of Fragile X mental retardation protein in malformative lesions of patients with focal cortical dysplasia.

Tue, 08/25/2020 - 06:12
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Increased expression of Fragile X mental retardation protein in malformative lesions of patients with focal cortical dysplasia.

Neuroreport. 2020 Aug 20;:

Authors: Reynolds CD, Nolan SO, Smith GD, Jefferson TS, Hodges SL, Brewster AL, Lugo JN

Abstract
OBJECTIVE: Focal cortical dysplasia (FCD) accounts for nearly half of all cases of medically refractory epilepsy in the pediatric and adult patient populations. This neurological disorder stems from localized malformations in cortical brain tissue due to impaired neuronal proliferation, differentiation, and migration patterns. Recent studies in animal models have highlighted the potential role of the Fragile X mental retardation protein (FMRP) levels in FCD. The purpose of this study was to investigate the status of FMRP activation in cortical brain tissues surgically resected from patients with FCD. In parallel, this study also investigated protein levels within the PI3K/AKT/mTOR and canonical Wnt signaling pathways.
METHODS: Pathologic tissue from malformative lesions of FCD patients with medically refractory epilepsy was compared to relatively normal control non-epileptic tissue from patients with intracranial neoplasms. A series of western blotting assays were performed to assess key proteins in the PI3K/AKT/mTOR, canonical Wnt signaling pathways, and FMRP.
RESULTS: There was suppression of S235/236-phosphorylated S6, GSK3α, and GSK3β protein levels in samples derived from FCD patients, compared to non-epileptic controls. FCD samples also had significantly greater levels of total and S499-phosphorylated FMRP.
CONCLUSION: These findings support our hypothesis that malformative lesions associated with FCD are characterized by high levels of FMRP activation along with dysregulation of both PI3K/AKT/mTOR and canonical Wnt signaling. These novel clinical findings extend previous work in animal models, further suggesting a potential unforeseen role of GSK3α, and GSK3β in the pathophysiology of FCD and refractory epilepsy.

PMID: 32833881 [PubMed - as supplied by publisher]

A positive, growth-based PAM screen identifies noncanonical motifs recognized by the S. pyogenes Cas9.

Tue, 08/25/2020 - 06:12
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A positive, growth-based PAM screen identifies noncanonical motifs recognized by the S. pyogenes Cas9.

Sci Adv. 2020 Jul;6(29):eabb4054

Authors: Collias D, Leenay RT, Slotkowski RA, Zuo Z, Collins SP, McGirr BA, Liu J, Beisel CL

Abstract
CRISPR technologies have overwhelmingly relied on the Streptococcus pyogenes Cas9 (SpyCas9), with its consensus NGG and less preferred NAG and NGA protospacer-adjacent motifs (PAMs). Here, we report that SpyCas9 also recognizes sequences within an N(A/C/T)GG motif. These sequences were identified on the basis of preferential enrichment in a growth-based screen in Escherichia coli. DNA binding, cleavage, and editing assays in bacteria and human cells validated recognition, with activities paralleling those for NAG(A/C/T) PAMs and dependent on the first two PAM positions. Molecular-dynamics simulations and plasmid-clearance assays with mismatch-intolerant variants supported induced-fit recognition of an extended PAM by SpyCas9 rather than recognition of NGG with a bulged R-loop. Last, the editing location for SpyCas9-derived base editors could be shifted by one nucleotide by selecting between (C/T)GG and adjacent N(C/T)GG PAMs. SpyCas9 and its enhanced variants thus recognize a larger repertoire of PAMs, with implications for precise editing, off-target predictions, and CRISPR-based immunity.

PMID: 32832642 [PubMed - as supplied by publisher]

Correlates of Nonmedical Prescription Opioid Use Among U.S. Adolescents.

Tue, 08/25/2020 - 06:12
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Correlates of Nonmedical Prescription Opioid Use Among U.S. Adolescents.

Am J Prev Med. 2019 11;57(5):e175-e179

Authors: Barnett TE, Thompson EL, Litt DM, Lewis MA

Abstract
INTRODUCTION: The purpose of this study is to assess risk factors, including other substance use, for nonmedical prescription opioid use among U.S. adolescents.
METHODS: A secondary data analysis of the 2017 Youth Risk Behavior Survey was conducted (n=10,175) in 2018. The outcome was nonmedical prescription opioid use. Predictor variables included other substance use, mood, sleep, academic performance, and demographic characteristics. Survey-weighted procedures in SAS, version 9.4 were used, and an adjusted logistic regression model was conducted.
RESULTS: Among the sampled adolescents, 13.8% (95% confidence limit=12.4%, 15.3%) reported nonmedical prescription opioid use. Nonmedical prescription opioid use was more likely among participants aged 15 years (versus 16 years), American Indian/Alaskan Natives, and those who reported being sad or hopeless. All other substance use was significantly associated with increased odds of nonmedical prescription opioid use. Nonmedical prescription opioid use was 1.5 times more likely among electronic vapor users (AOR=1.58, 95% CI=1.34, 1.86), 2 times more likely among cigarette (AOR=2.49, 95% CI=2.16, 2.88) and marijuana users (AOR=2.45, 95% CI=2.05, 2.93), and almost 3 times as likely among alcohol users (AOR=2.98, 95% CI=2.18, 4.07).
CONCLUSIONS: Study findings suggest a need for more interventions for nonmedical prescription opioid use among adolescents in the U.S. Information on nonmedical prescription opioid use should be added to all substance use prevention programs for adolescents. Moreover, future research needs to identify longitudinal predictors of adolescent nonmedical prescription opioid use to inform prevention efforts.

PMID: 31564603 [PubMed - indexed for MEDLINE]

Trunk muscle activity during pressure feedback monitoring among individuals with and without chronic low Back pain.

Mon, 08/24/2020 - 05:23

Trunk muscle activity during pressure feedback monitoring among individuals with and without chronic low Back pain.

BMC Musculoskelet Disord. 2020 Aug 22;21(1):569

Authors: Li X, Lo WLA, Lu SW, Liu H, Lin KY, Lai JY, Li L, Wang CH

Abstract
BACKGROUND: Pressure biofeedback unit (PBU) is a widely used non-invasive device to assist core muscle training by providing pressure feedback. The aim this study was to compare the muscle activities of transverse abdominis (TA) and multifidus (MF) at different target pressures (50, 60 and 70 mmHg) of PBU between individuals with and without cLBP.
METHODS: Twenty-two patients with chronic LBP (cLBP) and 24 age matched healthy individuals were recruited. Electromyography (EMG) signals were recorded from the TA and MF muscles while the TA and MF were contracted to achieve PBU pressure value of 50, 60 and 70 mmHg in random order. The average EMG amplitude (AEMG) of 3 replicate trials was used in the analysis after normalization to %MVIC. %MVIC is defined as the mean of the three AEMG divided by the AEMG of MVIC. Two-way ANOVA was performed to assess the effects of groups (healthy and cLBP) and the three different target pressures of PBU. Independent sample t-test was conducted to compare between the two groups. Spearman's correlation analysis was performed in the cLBP group to determine potential correlations between EMG activity, NPRS and ODI.
RESULTS: The %MVIC of the TA and MF in the cLBP group were higher than the control group at each pressure value (P<0.05). During maximal voluntary isometric contraction (MVIC) of TA and MF, compared with healthy groups, cLBP subjects showed a decrease (TA mean = 47.61 μV; MF mean = 42.40 μV) in EMG amplitudes (P ≤ 0.001). The MVIC of MF was negatively correlated with Numerical Pain Rating Scale (r = - 0.48, P = 0.024) and Oswestry Disability Index (r = - 0.59, P = 0.004).
CONCLUSIONS: We measured the trunk muscles activities at different PBU pressure values, which allows the individual to estimate trunk muscle contraction via PBU. Clinicians may be able to confer the data obtained through EMG recordings to adjust the exercise intensity of PBU training accordingly.

PMID: 32828131 [PubMed - as supplied by publisher]

Hexobarbital Sleep Test for Predicting the Susceptibility or Resistance to Experimental Posttraumatic Stress Disorder.

Sun, 08/23/2020 - 07:00
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Hexobarbital Sleep Test for Predicting the Susceptibility or Resistance to Experimental Posttraumatic Stress Disorder.

Int J Mol Sci. 2020 Aug 17;21(16):

Authors: Komelkova M, Manukhina E, Downey HF, Sarapultsev A, Cherkasova O, Kotomtsev V, Platkovskiy P, Fedorov S, Sarapultsev P, Tseilikman O, Tseilikman D, Tseilikman V

Abstract
Hexobarbital sleep test (HST) was performed in male Wistar rats (hexobarbital 60 mg/kg, i.p.) 30 days prior to stress exposure. Based on the duration of hexobarbital-induced sleep, rats were divided into two groups, animals with high intensity (fast metabolizers (FM), sleep duration <15 min) or low intensity of hexobarbital metabolism (slow metabolizers (SM), sleep duration ≥15 min). The SM and FM groups were then divided into two subgroups: unstressed and stressed groups. The stressed subgroups were exposed to predator scent stress for 10 days followed by 15 days of rest. SM and FM rats from the unstressed group exhibited different behavioral and endocrinological patterns. SM showed greater anxiety and higher corticosterone levels. In stressed animals, anxiety-like posttraumatic stress disorder (PTSD) behavior was aggravated only in SM. Corticosterone levels in the stressed FM, PTSD-resistant rats, were lower than in unstressed SM. Thus, HST was able to predict the susceptibility or resistance to experimental PTSD, which was consistent with the changes in glucocorticoid metabolism.

PMID: 32824478 [PubMed - as supplied by publisher]

Effect of functional electrical stimulation plus body weight-supported treadmill training for gait rehabilitation in patients with poststroke: a retrospective case-matched study.

Thu, 08/20/2020 - 07:31
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Effect of functional electrical stimulation plus body weight-supported treadmill training for gait rehabilitation in patients with poststroke: a retrospective case-matched study.

Eur J Phys Rehabil Med. 2020 Feb;56(1):34-40

Authors: Bao X, Luo JN, Shao YC, Tang ZQ, Liu HY, Liu H, Tan JW

Abstract
BACKGROUND: Functional electrical stimulation (FES) plus body weight-supported treadmill training (BWSTT) provide effective gait training for poststroke patients with abnormal gait. These features promote a successful active motor relearning of ambulation in stroke survivors.
AIM: This is a retrospective study to assess the effect of FES plus BWSTT for gait rehabilitation in patients poststroke.
DESIGN: A retrospective case-matched study.
SETTING: Participants were recruited from a rehabilitation department in an acute university-affiliated hospital POPULATION: Ninety patients poststroke from Yue Bei People's Hospital underwent BWSTT (A: control group) were compared to an equal number of cross-matched patients who received FES plus BWSTT (B: FES plus BWSTT group).
METHODS: While B group received FES for 45 minutes plus BSWTT for 30 minutes in the program, group A received time-matched BWSTT alone. The walking speed, step length, step cadence, Fugl-Meyer Lower-Limb Scale (LL-FMA), composite spasticity scale (CSS), 10-Meter Walk Test (10MWT), Tinetti Balance Test (TBT) and nerve physiology testing were collected before and after intervention.
RESULTS: One hundred and eighty patients with poststroke abnormal gait were chosen. There were significant differences in walking speed, step length, step cadence, LL-FMA, CSS, TBT, and 10MWT between baseline and postintervention (P<0.05). There were significant differences in walking speed, step length, step cadence, LL-FMA, CSS, TBT, and 10MWT between two groups at the end of the eighth week (P<0.05), but not at baseline (P>0.05). In comparison with group A, the peak of somatosensory evoked potential (SEP) and motor evoked potential (MEP) amplitude increased, the latency was shortened, and the conduction velocity of sensory nerve (SCV) and motor nerve (MCV) was significantly increased in the group B (P<0.05). No adverse events occurred during the study.
CONCLUSIONS: This study suggests that FES plus BWSTT could be more effective than BWSTT alone in the improvement of gait, balance, spasticity, and function of the lower limb in patients poststroke.
CLINICAL REHABILITATION IMPACT: Introduce effective rehabilitation strategies for poststroke patients with abnormal gait.

PMID: 31615194 [PubMed - indexed for MEDLINE]

Understanding perceived usefulness and actual use of protective behavioral strategies: The role of perceived norms for the reasons that young adult drinkers use protective behavioral strategies.

Tue, 08/18/2020 - 06:09

Understanding perceived usefulness and actual use of protective behavioral strategies: The role of perceived norms for the reasons that young adult drinkers use protective behavioral strategies.

Addict Behav. 2020 Jul 31;112:106585

Authors: Fairlie AM, Lewis MA, Waldron KA, Wallace EC, Lee CM

Abstract
INTRODUCTION: The current study examines the norms-behavior link by investigating a novel cognition for protective behavioral strategies (PBS)-descriptive and injunctive norms for close friends' reasons to use PBS (e.g., limit drinking, reduce consequences)-in relation to one's own perception of usefulness and personal use of PBS. Further, we tested whether the association between perceived norms for reasons to use PBS and personal PBS use was mediated by perceived usefulness of PBS.
METHODS: College student drinkers ages 18-24 [N = 301; 53% female, 69% White, mean age = 20.16 years (SD = 1.54)] were recruited for a larger study. Eligible students reported alcohol use 2+ days a week and 1+ occasions of heavy episodic drinking in the last two weeks. Linear regression tested whether descriptive and injunctive norms for reasons to use PBS were associated with perceived usefulness and personal use of PBS; path analysis was used to test mediation. All analyses were conducted by PBS subscale (limiting/stopping, serious harm reduction, manner of drinking).
RESULTS: Descriptive norms for reasons to use PBS (i.e., perceptions that close friends use PBS to reduce drinking/consequences) were positively associated with perceived usefulness and personal PBS use for limiting/stopping and to some extent manner of drinking. For each subscale, the association between descriptive norms for reasons to use PBS and personal PBS use was mediated by perceived usefulness of PBS. Results were not significant for injunctive norms.
CONCLUSIONS: Findings suggest descriptive norms, rather than injunctive norms, for close friends' reasons to use PBS, may be relevant for inclusion in brief interventions.

PMID: 32805540 [PubMed - as supplied by publisher]

Synergistic Effect and Antibiofilm Activity of a Skin and Wound Cleanser.

Tue, 08/18/2020 - 06:09

Synergistic Effect and Antibiofilm Activity of a Skin and Wound Cleanser.

Wounds. 2020 May 07;:

Authors: Salamone AB, Salamone JC, McMahon RE, Poleon S, Bionda N, D'Arpa P

Abstract
INTRODUCTION: Biofilm in chronic wounds impedes the wound healing process. Each biofilm has differing characteristics requiring a multifaceted approach for removal while maintaining a surrounding environment conducive to wound healing.
OBJECTIVE: In this study, 3 of the components in a wound cleanser are tested to determine synergy in eradicating biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in vitro.
MATERIALS AND METHODS: The 3 components assessed for synergy were ethylenediamine tetraacetic acid sodium salts (EDTA), vicinal diols (VD; ethylhexylglycerin and octane-1,2-diol), and polyhexamethylene biguanide (PHMB). Each component was assessed individually and in combination while dissolved in a base solution. The Calgary assay method was used for biofilm growth and treatment. Kull Equation analysis for synergy was conducted using viable count results.
RESULTS: Synergy is defined as the interaction of components to produce a combined effect greater than the sum of their separate effects. The base solution containing all 3 components (EDTA, VD, and PHMB) reduced biofilm viability by more than 5 logs, demonstrating statistically significant synergy. The 3 components tested individually in the base solution resulted in the following: EDTA did not reduce bacteria viability; VD reduced viability by about 1 log; and PHMB reduced P aeruginosa viability by about 2.5 logs and MRSA viability by about 4 logs. Of importance, the MRSA biofilm failed to regrow in the recovery plates after combined treatment, indicating complete elimination of the biofilm bacteria.
CONCLUSIONS: The experimental and calculated results indicate the 3 components (VD, EDTA, and PHMB) when used together act synergistically to eradicate MRSA and P aeruginosa biofilms in vitro.

PMID: 32804659 [PubMed - as supplied by publisher]

A Novel Syndrome With Short Stature, Mandibular Hypoplasia, and Osteoporosis May Be Associated With a PRRT3 Variant.

Tue, 08/18/2020 - 06:09

A Novel Syndrome With Short Stature, Mandibular Hypoplasia, and Osteoporosis May Be Associated With a PRRT3 Variant.

J Endocr Soc. 2020 Aug 01;4(8):bvaa088

Authors: Garg A, El-Shanti H, Xing C, Zhou Z, Abujbara M, Al-Rashed K, El-Khateeb M, Ajlouni K, Agarwal AK

Abstract
Context: Despite considerable progress in elucidating the molecular basis of various progeroid syndromes, some rare patients remain unexplained.
Objective: To elucidate molecular genetic basis of a novel autosomal recessive progeroid syndrome.
Participants: A 24-year-old male and his 18-year-old sister with short stature, mandibular hypoplasia, pointed nose, shrill voice, severe osteoporosis, and short eyebrows and their unaffected siblings and parents belonging to a consanguineous Arab family.
Results: Using exome and Sanger sequencing, we report a novel homozygous p.Glu394Lys disease-causing variant in proline-rich transmembrane protein 3 (PRRT3). PRRT3 belongs to the family of proline-rich proteins containing several repeats of a short proline-rich sequence, but its function remains to be determined. Preliminary observations showing colocalization of Prrt3 and synaptophysin support its role in vesicle exocytosis. Consistent with the highest messenger ribonucleic acid expression of PRRT3 in the pituitary, both the patients had mild growth hormone deficiency but had near normal reproductive development.
Conclusions: We conclude that the homozygous p.Glu394Lys variant in PRRT3 may be associated with a novel autosomal recessive, progeroid syndrome with short stature, mandibular hypoplasia, osteoporosis, short eyebrows, and mild growth hormone (GH) deficiency. Our findings extend the spectrum of progeroid syndromes and elucidate important functions of PRRT3 in human biology, including secretion of GH from the pituitary.

PMID: 32803092 [PubMed - as supplied by publisher]

Uterine perivascular adipose tissue is a novel mediator of uterine artery blood flow and reactivity in rat pregnancy.

Tue, 08/18/2020 - 06:09
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Uterine perivascular adipose tissue is a novel mediator of uterine artery blood flow and reactivity in rat pregnancy.

J Physiol. 2019 08;597(15):3833-3852

Authors: Osikoya O, Ahmed H, Panahi S, Bourque SL, Goulopoulou S

Abstract
KEY POINTS: In vivo, uterine perivascular adipose tissue (PVAT) potentiates uterine artery blood flow in pregnant rats, although not in non-pregnant rats. In isolated preparations, uterine PVAT has pro-contractile and anti-dilatory effects on uterine arteries. Pregnancy induces changes in uterine arteries that makes them responsive to uterine PVAT signalling.
ABSTRACT: An increase in uterine artery blood flow (UtBF) is a common and necessary feature of a healthy pregnancy. In the present study, we tested the hypothesis that adipose tissue surrounding uterine arteries (uterine perivascular adipose tissue; PVAT) is a novel local mediator of UtBF and uterine artery tone during pregnancy. In vivo experiments in anaesthetized Sprague-Dawley rats showed that pregnant animals (gestational day 16, term = 22--23 days) had a three-fold higher UtBF compared to non-pregnant animals. Surgical removal of uterine PVAT reduced UtBF only in pregnant rats. In a series of ex vivo bioassays, we demonstrated that uterine PVAT had pro-contractile and anti-dilatory effects on rat uterine arteries. In the presence of PVAT-conditioned media, isolated uterine arteries from both pregnant and non-pregnant rats had reduced vasodilatory responses. In non-pregnant rats, these responses were mediated at the level of uterine vascular smooth muscle, whereas, in pregnant rats, PVAT-media reduced endothelium-dependent relaxation. Pregnancy increased adipocyte size in ovarian adipose tissue but had no effect on uterine PVAT adipocyte morphology. In addition, pregnancy down-regulated the gene expression of metabolic adipokines in uterine but not in aortic PVAT. In conclusion, this is the first study to demonstrate that uterine PVAT plays a regulatory role in UtBF, at least in part, as a result of its actions on uterine artery tone. We propose that the interaction between the uterine vascular wall and its adjacent adipose tissue may provide new insights for interventions in pregnancies with adipose tissue dysfunction and abnormal UtBF.

PMID: 31165480 [PubMed - indexed for MEDLINE]

What happens to agreement over time? A longitudinal study of self-reported substance use compared to saliva toxicological testing among subsidized housing residents.

Sat, 08/15/2020 - 06:36
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What happens to agreement over time? A longitudinal study of self-reported substance use compared to saliva toxicological testing among subsidized housing residents.

J Subst Abuse Treat. 2019 06;101:12-17

Authors: Rendon A, Mun EY, Spence-Almaguer E, Walters ST

Abstract
The agreement between self-reported and toxicologically verified substance use provides important information about the validity of self-reported use. While some studies report aggregate agreement across follow-up points, only a few have examined the agreement at each time point separately. An overall rate of agreement across time may miss changes that occur as people progress through a research study. In this study, a sample of 644 adults (43.8% male, 32.6% White, 57.0% Black, 90.2% ages 36+) residing in subsidized housing was used to determine the agreement between self-reported use and saliva toxicological testing for marijuana, cocaine, PCP, amphetamine, and methamphetamine at three different time points. Agreement between saliva toxicological testing and self-report ranged between 84.2% and 94.3% for different substances over time. Higher rates of agreement were found for cocaine than had been reported by previous studies. Statistically significant differences in the odds ratios of concordance over time (baseline, 6-month, and 12-month follow-up) were found for marijuana and the combined category for PCP, amphetamine, and methamphetamine. Our findings suggest that oral fluid drug tests generally withstand community field assessments and result in relatively high levels of agreement for marijuana, cocaine, PCP, amphetamine, and methamphetamine use, when compared to self-report. Because of the ease of sample collection and low chance of adulteration, we conclude that saliva testing is a viable method for toxicological confirmation of substance use behavior in this setting.

PMID: 31174709 [PubMed - indexed for MEDLINE]

How many familial relationship testing results could be wrong?

Fri, 08/14/2020 - 06:06

How many familial relationship testing results could be wrong?

PLoS Genet. 2020 Aug;16(8):e1008929

Authors: Ge J, Budowle B

PMID: 32790673 [PubMed - as supplied by publisher]

Thymic rejuvenation via FOXN1-reprogrammed embryonic fibroblast (FREF) to counteract age-related inflammation.

Fri, 08/14/2020 - 06:06

Thymic rejuvenation via FOXN1-reprogrammed embryonic fibroblast (FREF) to counteract age-related inflammation.

JCI Insight. 2020 Aug 13;:

Authors: Oh J, Wang W, Thomas R, Su DM

Abstract
Age-associated systemic, chronic inflammation is partially attributed to increased self (auto)-reactivity, resulting from disruption of central tolerance in the aged, involuted thymus. This involution causally results from gradually decreased expression of the transcription factor FOXN1 in thymic epithelial cells (TECs), while exogenous FOXN1 in TECs can partially rescue age-related thymic involution. Given the findings that TECs induced from FOXN1-overexpressing embryonic fibroblasts can generate an ectopic de novo thymus under the kidney capsule and intra-thymically injected naturally young TECs can lead to middle-aged thymus regrowth, we attempted to extend these two findings by combining them as a novel thymic rejuvenation strategy with two types of promoter-driven (Rosa26CreERT and FoxN1Cre) Cre-mediated FOXN1-reprogrammed embryonic fibroblasts (FREFs). We engrafted these two-types of FREFs directly into the aged murine thymus. We found significant regrowth of the native aged thymus with rejuvenated architecture and function in both males and females, exhibiting increased thymopoiesis and reinforced thymocyte negative selection, along with reduced senescent T cells and auto-reactive T cell-mediated inflammation in old mice. Therefore, this strategy has preclinical significance and presents a strategy to potentially rescue decreased thymopoiesis and perturbed negative selection to significantly, albeit partially, restore defective central tolerance and reduce subclinical autoimmune symptoms in the elderly.

PMID: 32790650 [PubMed - as supplied by publisher]

Mechanistic studies of cytotoxic activity of the mesoionic compound MIH 2.4Bl in MCF-7 breast cancer cells.

Thu, 08/13/2020 - 07:58
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Mechanistic studies of cytotoxic activity of the mesoionic compound MIH 2.4Bl in MCF-7 breast cancer cells.

Oncol Lett. 2020 Sep;20(3):2291-2301

Authors: de Mascena Costa LA, Debnath D, Harmon AC, de Sousa Araújo S, da Silva Souza HD, de Athayde Filho PF, Wischral A, Adrião Gomes Filho M, Mathis JM

Abstract
In the present study, the cytotoxic effects of a 1,3-thiazolium-5-thiolate derivative of a mesoionic compound, MIH 2.4Bl, were assessed in the MCF-7 breast cancer cell line. The cytotoxic effects of MIH 2.4Bl were determined using a crystal violet assay. Using a dose-response curve, the IC50 value of MIH 2.4Bl was determined to be 45.8±0.8 µM. Additionally, the effects of MIH 2.4Bl on mitochondrial respiration were characterized using oxygen consumption rate analysis. Treating MCF-7 cells with increasing concentrations of MIH 2.4Bl resulted in a significant reduction in all mitochondrial respiratory parameters compared with the control cells, indicative of an overall decrease in mitochondrial membrane potential. The induction of autophagy by MIH 2.4Bl was also examined by measuring changes in the expression of protein markers of autophagy. As shown by western blot analysis, treatment of MCF-7 cells with MIH 2.4Bl resulted in increased protein expression levels of Beclin-1 and ATG5, as well as an increase in the microtubule-associated protein 1A/1B light chain 3B (LC3B)-II to LC3B-I ratio compared with the control cells. Microarray analysis of changes in gene expression following MIH 2.4Bl treatment demonstrated 3,659 genes exhibited a fold-change ≥2. Among these genes, 779 were up-regulated, and 2,880 were down-regulated in cells treated with MIH 2.4Bl compared with the control cells. Based on the identity of the transcripts and fold-change of expression, six genes were selected for verification by reverse transcription-quantitative (RT-q)PCR; activating transcription factor 3, acidic repeat-containing protein, heparin-binding EGF-like growth factor, regulator of G-protein signaling 2, Dickkopf WNT signaling pathway inhibitor 1 and adhesion molecule with Ig like domain 2. The results of RT-qPCR analysis of RNA isolated from control and MIH 2.4Bl treated cells were consistent with the expression changes identified by microarray analysis. Together, these results suggest that MIH 2.4Bl may be a promising candidate for treating breast cancer and warrants further in vitro and in vivo investigation.

PMID: 32782546 [PubMed]

The effect of intermittent hypoxia training on migraine: a randomized controlled trial.

Tue, 08/11/2020 - 06:09

The effect of intermittent hypoxia training on migraine: a randomized controlled trial.

Am J Transl Res. 2020;12(7):4059-4065

Authors: Bao X, Liu H, Liu HY, Long Y, Tan JW, Zhu ZM

Abstract
OBJECTIVE: To study the effect of intermittent hypoxia training (IHT) for migraine.
DESIGN: A single-blind, randomized controlled trial. All participants were recruited from a rehabilitation department in an acute university-affiliated hospital.
METHODS: Participants with migraines were randomly assigned to two groups (IHT group and control group). The Migraine Disability Assessment (MIDAS), Visual Analog Scale (VAS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Vascular endothelial growth factor (VEGF), calcitonin gene related peptide (CGRP) and cerebrovascular hemodynamic parameters were collected at baseline and end of the 8th week. The attack frequencies of migraines were evaluated at 3 months.
RESULTS: Among the 48 subjects, five males and forty-three females, the ages ranged from 19 to 53 years old (mean ± SD = 31.3±7.78). MIDAS, SF-36, VAS, BAI, BDI, VEGF, CGRP and cerebrovascular hemodynamic parameters were improved after IHT intervention. There were significant differences between IHT group and the control group in MIDAS, SF-36, VAS, BAI, BDI, VEGF, CGRP and cerebrovascular hemodynamic parameters at the end of the 8th weeks (P<0.05). Attack frequencies were improved within 3 months after IH training intervention (P<0.01), but not in the control group (P>0.05). No adverse events occurred during the study.
CONCLUSION: IHT could improve migraines after intervention up to three months. IHT could be an effective method for relieving a migraine.

PMID: 32774759 [PubMed - as supplied by publisher]

Comment on: Curative-intent radiotherapy for pediatric osteosarcoma: The St. Jude experience.

Tue, 08/11/2020 - 06:09
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Comment on: Curative-intent radiotherapy for pediatric osteosarcoma: The St. Jude experience.

Pediatr Blood Cancer. 2020 06;67(6):e28287

Authors: Vicenzi P, Johnnidis M, Hamby T, Ray A

PMID: 32293779 [PubMed - indexed for MEDLINE]

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