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Reducing Intracranial Pressure by Reducing Central Venous Pressure: Assessment of potential countermeasures to spaceflight associated neuro-ocular syndrome.

Recent Research Articles from UNTHSC - Fri, 12/04/2020 - 06:08
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Reducing Intracranial Pressure by Reducing Central Venous Pressure: Assessment of potential countermeasures to spaceflight associated neuro-ocular syndrome.

J Appl Physiol (1985). 2020 Dec 03;:

Authors: Hansen AB, Lawley JS, Rickards CA, Howden EJ, Sarma S, Cornwell WK, Amin SB, Mugele H, Marume K, Possnig C, Whitworth LA, Williams MA, Levine BD

Abstract
Spaceflight-associated neuro-ocular syndrome (SANS) involves unilateral or bilateral optic disc edema, widening of the optic nerve sheath, and posterior globe flattening. Due to posterior globe flattening, it is hypothesized that microgravity causes a disproportionate change in intracranial pressure (ICP) relative to intraocular pressure. Countermeasures capable of reducing ICP include thigh cuffs and breathing against inspiratory resistance. Due to the coupling of central venous (CVP) and intracranial pressure, we hypothesized that both ICP and CVP will be reduced during both countermeasures. In four male participants (32±13 yrs) who were previously implanted with Ommaya reservoirs for treatment of unrelated clinical conditions, ICP was measured invasively through these ports. Subjects were healthy at the time of testing. CVP was measured invasively by a peripherally inserted central catheter. Participants breathed through an Impedance Threshold Device (ITD, -7 cm.H2O) to generate negative intrathoracic pressure for five-mins, and subsequently, wore bilateral thigh cuffs at 30-mmHg for two-mins. Breathing through an ITD reduced both CVP (6±2 vs 3±1 mmHg; P=0.02) and ICP (16±3 vs 12±1 mmHg; P=0.04) compared to the supine posture, which was not observed during the free breathing condition (CVP, 6±2 vs 6±2 mmHg; P=0.87 and ICP, 15±3 vs 15±4 mmHg; P=0.68). Inflation of the thigh cuffs to 30-mmHg caused no meaningful reduction in CVP in all four individuals (5±4 vs 5±4 mmHg; P=0.1), coincident with a minimal reduction in ICP (15±3 vs 14±4 mmHg; P=0.13). The application of inspiratory resistance breathing resulted in reductions in both ICP and CVP, likely due to intrathoracic unloading.

PMID: 33270516 [PubMed - as supplied by publisher]

Of Cross-immunity, Herd Immunity and Country-specific Plans: Experiences from COVID-19 in India.

Recent Research Articles from UNTHSC - Fri, 12/04/2020 - 06:08
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Of Cross-immunity, Herd Immunity and Country-specific Plans: Experiences from COVID-19 in India.

Aging Dis. 2020 Dec;11(6):1339-1344

Authors: Chakrabarti SS, Kaur U, Singh A, Chakrabarti S, Krishnatreya M, Agrawal BK, Mittal A, Singh A, Khanna R, Gambhir IS, Jin K, Chakrabarti S

Abstract
India has witnessed a high number of COVID-19 cases, but mortality has been quite low, and most cases have been asymptomatic or mild. In early April, we had hypothesized a low COVID-19 mortality in India, based on the concept of cross-immunity. The presence of cross-immunity is presumed to lead to a milder course of disease and allow the time necessary for the development of adaptive immunity by the body to eliminate the virus. Evidence supporting our hypothesis has started showing up. Multiple studies have shown the generation of different T cell subsets and B cells responding to epitopes of viral proteins, especially of the spike protein, as a part of adaptive immunity against SARS-CoV-2. Cross-reactive T-cells have been demonstrated in patients who have been previously exposed to endemic coronaviruses. The interplay of cross-immunity and herd immunity is apparent in the COVID-19 scenario in India from the presence of a large number of asymptomatic or mild cases, a low infection-fatality ratio and a generally flat curve of percentage positivity of cases with respect to total testing, both in periods of strict lock-down and step-wise unlocking. It seems that cross-immunity resulted in faster generation of herd immunity. Although the initial restrictive measures such as lockdown prevented the rapid spread of the outbreak, further extension of such measures and overly expensive ones such as enhanced testing in India will result in a huge burden on the health economics as well as the society. Hence, we propose a restructuring of the health services and approach to COVID-19. The restructured health services should move away from indiscriminate testing, isolation and quarantine, and instead, the emphasis should be on improving facilities for testing and management of only critical COVID cases and the replacement of complete lockdowns by the selective isolation and quarantine of susceptible persons such as the aged and those with co-morbidities. In the process of describing India-specific plans, we emphasize why the development of country-specific plans for tackling epidemics is important, instead of adopting a "one policy fits all" approach.

PMID: 33269091 [PubMed]

Host antibacterial defense of 6-10 Gy γ-irradiated mice subjected to lentiviral vector-based Gas5 gene therapy.

Recent Research Articles from UNTHSC - Thu, 12/03/2020 - 07:18
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Host antibacterial defense of 6-10 Gy γ-irradiated mice subjected to lentiviral vector-based Gas5 gene therapy.

Gene Ther. 2020 Dec 01;:

Authors: Ito I, Loucas BD, Suzuki S, Kobayashi M, Suzuki F

Abstract
Gut bacteria-associated sepsis is a serious concern in patients with gastrointestinal acute radiation syndrome (GIARS). In our previous studies, all mice exposed to 8 Gy of whole body γ-irradiation (8 Gy GIARS-mice) died by sepsis stemming from bacterial translocation. M1Mϕ located in the bacterial translocation site (i.e., the mesenteric lymph nodes, MLNs) have been characterized as major antibacterial effector cells. However, M2bMϕ, inhibitor cells for M1Mϕ polarization, predominated in the MLNs of these mice. The reduced expression of long noncoding RNA Gas5 was associated with M2bMϕ polarization. In this study, we tried to reduce the mortality rate of 8 Gy GIARS-mice through Gas5 gene transduction using lentivirus (Gas5 lentivirus). After Gas5 lentivirus injection, Gas5 RNA was overexpressed in MLN-F4/80+ cells of 8 Gy GIARS-mice, and these cells were identified as non-M2bMϕ. All of the 8 Gy GIARS-mice injected with Gas5 lentivirus survived 30 days or more after irradiation, and bacterial translocation and subsequent sepsis were shown to be minimal in these mice. These results indicate that the antibacterial resistance of 8 Gy GIASR-mice can be restored through the modulation of M2bMϕ located in the bacterial translocation site by Gas5 transduction.

PMID: 33262512 [PubMed - as supplied by publisher]

Age, gender, and racial/ethnic differences in the association of triclocarban with adulthood obesity using NHANES 2013-2016.

Recent Research Articles from UNTHSC - Wed, 12/02/2020 - 09:28
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Age, gender, and racial/ethnic differences in the association of triclocarban with adulthood obesity using NHANES 2013-2016.

Arch Environ Occup Health. 2020 Dec 01;:1-8

Authors: Uche UI, King CC

Abstract
This study examined the association between triclocarban and obesity among US adults and compared the pattern of this association across age, gender, and racial/ethnic groups. Study found triclocarban to be associated with obesity (OR: OR:1.123 95% CI: 1.046, 1.205) and this association remained among women (OR:1.14 95% CI: 1.031, 1.261). Study participants aged 60 years and older were more likely to be overweight (OR:1.131 95% CI: 1.022 1.251) and obese (OR:1.192 95% CI: 1.079, 1.317) when compared to other age groups. Likewise, non-Hispanic whites (OR:1.126 95% CI: 1.003, 1.263) and "other race including multi-racial" (OR:1.431 95% CI: 1.219, 1.679) were more likely to be obese when compared to other racial/ethnic groups. In conclusion, triclocarban is associated with obesity among US adults and there is evidence of gender, age, and racial/ethnicity differences in the association.

PMID: 33256559 [PubMed - as supplied by publisher]

Kupffer Cells: Inflammation Pathways and Cell-Cell Interactions in Alcohol-Associated Liver Disease.

Recent Research Articles from UNTHSC - Wed, 12/02/2020 - 09:28
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Kupffer Cells: Inflammation Pathways and Cell-Cell Interactions in Alcohol-Associated Liver Disease.

Am J Pathol. 2020 11;190(11):2185-2193

Authors: Slevin E, Baiocchi L, Wu N, Ekser B, Sato K, Lin E, Ceci L, Chen L, Lorenzo SR, Xu W, Kyritsi K, Meadows V, Zhou T, Kundu D, Han Y, Kennedy L, Glaser S, Francis H, Alpini G, Meng F

Abstract
Chronic alcohol consumption is linked to the development of alcohol-associated liver disease (ALD). This disease is characterized by a clinical spectrum ranging from steatosis to hepatocellular carcinoma. Several cell types are involved in ALD progression, including hepatic macrophages. Kupffer cells (KCs) are the resident macrophages of the liver involved in the progression of ALD by activating pathways that lead to the production of cytokines and chemokines. In addition, KCs are involved in the production of reactive oxygen species. Reactive oxygen species are linked to the induction of oxidative stress and inflammation in the liver. These events are activated by the bacterial endotoxin, lipopolysaccharide, that is released from the gastrointestinal tract through the portal vein to the liver. Lipopolysaccharide is recognized by receptors on KCs that are responsible for triggering several pathways that activate proinflammatory cytokines involved in alcohol-induced liver injury. In addition, KCs activate hepatic stellate cells that are involved in liver fibrosis. Novel strategies to treat ALD aim at targeting Kupffer cells. These interventions modulate Kupffer cell activation or macrophage polarization. Evidence from mouse models and early clinical studies in patients with ALD injury supports the notion that pathogenic macrophage subsets can be successfully translated into novel treatment options for patients with this disease.

PMID: 32919978 [PubMed - indexed for MEDLINE]

Kynurenic Acid Protects Against Ischemia/Reperfusion-Induced Retinal Ganglion Cell Death in Mice.

Recent Research Articles from UNTHSC - Wed, 12/02/2020 - 09:28
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Kynurenic Acid Protects Against Ischemia/Reperfusion-Induced Retinal Ganglion Cell Death in Mice.

Int J Mol Sci. 2020 Mar 05;21(5):

Authors: Nahomi RB, Nam MH, Rankenberg J, Rakete S, Houck JA, Johnson GC, Stankowska DL, Pantcheva MB, MacLean PS, Nagaraj RH

Abstract
BACKGROUND: Glaucoma is an optic neuropathy and involves the progressive degeneration of retinal ganglion cells (RGCs), which leads to blindness in patients. We investigated the role of the neuroprotective kynurenic acid (KYNA) in RGC death against retinal ischemia/reperfusion (I/R) injury.
METHODS: We injected KYNA intravenously or intravitreally to mice. We generated a knockout mouse strain of kynurenine 3-monooxygenase (KMO), an enzyme in the kynurenine pathway that produces neurotoxic 3-hydroxykynurenine. To test the effect of mild hyperglycemia on RGC protection, we used streptozotocin (STZ) induced diabetic mice. Retinal I/R injury was induced by increasing intraocular pressure for 60 min followed by reperfusion and RGC numbers were counted in the retinal flat mounts.
RESULTS: Intravenous or intravitreal administration of KYNA protected RGCs against I/R injury. The I/R injury caused a greater loss of RGCs in wild type than in KMO knockout mice. KMO knockout mice had mildly higher levels of fasting blood glucose than wild type mice. Diabetic mice showed significantly lower loss of RGCs when compared with non-diabetic mice subjected to I/R injury.
CONCLUSION: Together, our study suggests that the absence of KMO protects RGCs against I/R injury, through mechanisms that likely involve higher levels of KYNA and glucose.

PMID: 32151061 [PubMed - indexed for MEDLINE]

Recent changes in cervical cancer screening guidelines: U.S. women's willingness for HPV testing instead of Pap testing.

Recent Research Articles from UNTHSC - Wed, 12/02/2020 - 09:28
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Recent changes in cervical cancer screening guidelines: U.S. women's willingness for HPV testing instead of Pap testing.

Prev Med. 2020 01;130:105928

Authors: Thompson EL, Galvin AM, Daley EM, Tatar O, Zimet GD, Rosberger Z

Abstract
Cervical cancer screening guidelines in the United States were revised in 2018 to include the option of primary human papillomavirus (HPV) testing. The transition to this screening method may face difficulties as Pap testing has been the primary screening modality in the United States. The objective of this study is to assess information, motivation, and behavioral skills associated with willingness to receive an HPV test instead of a Pap test among women. The sample included U.S. 812 women, ages 30 to 65 years. Participants completed an online survey in 2018. The Information, Motivation, and Behavioral Skills (IMB) model was used to measure predictors of willingness for HPV testing. The outcome variables were willingness to receive the HPV test instead of the Pap test, with and without time interval details. Logistic regression modeling was used with SAS 9.4. Over half of the sample (55%) were willing to receive the HPV test. For the information domain, HPV knowledge was significantly associated with willingness for HPV testing (OR = 1.08, 95%CI 1.04-1.13). Significant motivating factors included: positive attitudes, social norms, perceived benefits, worry about cervical cancer, and worry about abnormal HPV tests. For behavioral skills, women were significantly more willing to get the HPV test if a provider recommended it (OR = 2.43, 95%CI 1.53-3.87) and currently up-to-date on cervical cancer screening guidelines (OR = 1.52, 95%CI 1.52-2.26). Addressing barriers and facilitators to willingness to transition to primary HPV testing over Pap testing is needed as the United States has updated guidelines for cervical cancer screening.

PMID: 31756351 [PubMed - indexed for MEDLINE]

Store-operated calcium entry: Pivotal roles in renal physiology and pathophysiology.

Recent Research Articles from UNTHSC - Tue, 12/01/2020 - 05:10
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Store-operated calcium entry: Pivotal roles in renal physiology and pathophysiology.

Exp Biol Med (Maywood). 2020 Nov 29;:1535370220975207

Authors: Chaudhari S, Mallet RT, Shotorbani PY, Tao Y, Ma R

Abstract
Research conducted over the last two decades has dramatically advanced the understanding of store-operated calcium channels (SOCC) and their impact on renal function. Kidneys contain many types of cells, including those specialized for glomerular filtration (fenestrated capillary endothelium, podocytes), water and solute transport (tubular epithelium), and regulation of glomerular filtration and renal blood flow (vascular smooth muscle cells, mesangial cells). The highly integrated function of these myriad cells effects renal control of blood pressure, extracellular fluid volume and osmolality, electrolyte balance, and acid-base homeostasis. Many of these cells are regulated by Ca2+ signaling. Recent evidence demonstrates that SOCCs are major Ca2+ entry portals in several renal cell types. SOCC is activated by depletion of Ca2+ stores in the sarco/endoplasmic reticulum, which communicates with plasma membrane SOCC via the Ca2+ sensor Stromal Interaction Molecule 1 (STIM1). Orai1 is recognized as the main pore-forming subunit of SOCC in the plasma membrane. Orai proteins alone can form highly Ca2+ selective SOCC channels. Also, members of the Transient Receptor Potential Canonical (TRPC) channel family are proposed to form heteromeric complexes with Orai1 subunits, forming SOCC with low Ca2+ selectivity. Recently, Ca2+ entry through SOCC, known as store-operated Ca2+ entry (SOCE), was identified in glomerular mesangial cells, tubular epithelium, and renovascular smooth muscle cells. The physiological and pathological relevance and the characterization of SOCC complexes in those cells are still unclear. In this review, we summarize the current knowledge of SOCC and their roles in renal glomerular, tubular and vascular cells, including studies from our laboratory, emphasizing SOCE regulation of fibrotic protein deposition. Understanding the diverse roles of SOCE in different renal cell types is essential, as SOCC and its signaling pathways are emerging targets for treatment of SOCE-related diseases.

PMID: 33249888 [PubMed - as supplied by publisher]

Genome-Wide Methylation of Mild Cognitive Impairment in Mexican Americans Highlights Genes Involved in Synaptic Transport, Alzheimer's Disease-Precursor Phenotypes, and Metabolic Morbidities.

Recent Research Articles from UNTHSC - Tue, 12/01/2020 - 05:10
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Genome-Wide Methylation of Mild Cognitive Impairment in Mexican Americans Highlights Genes Involved in Synaptic Transport, Alzheimer's Disease-Precursor Phenotypes, and Metabolic Morbidities.

J Alzheimers Dis. 2019;72(3):733-749

Authors: Pathak GA, Silzer TK, Sun J, Zhou Z, Daniel AA, Johnson L, O'Bryant S, Phillips NR, Barber RC

Abstract
The Mexican American population is among the fastest growing aging population and has a younger onset of cognitive decline. This group is also heavily burdened with metabolic conditions such as hypertension, diabetes, and obesity. Unfortunately, limited research has been conducted in this group. Understanding methylation alterations, which are influenced by both genetic and lifestyle factors, is key to identifying and addressing the root cause for mild cognitive impairment, a clinical precursor for dementia. We conducted an epigenome-wide association study on a community-based Mexican American population using the Illumina EPIC array. Following rigorous quality control measures, we identified 10 CpG sites to be differentially methylated between normal controls and individuals with mild cognitive impairment annotated to PKIB, KLHL29, SEPT9, OR2C3, CPLX3, BCL2L2-PABPN1, and CCNY. We found four regions to be differentially methylated in TMEM232, SLC17A8, ALOX12, and SEPT8. Functional gene-set analysis identified four gene-sets, RIN3, SPEG, CTSG, and UBE2L3, as significant. The gene ontology and pathway analyses point to neuronal cell death, metabolic dysfunction, and inflammatory processes. We found 1,450 processes to be enriched using empirical Bayes gene-set enrichment. In conclusion, the functional overlap of differentially methylated genes associated with cognitive impairment in Mexican Americans implies cross-talk between metabolically-instigated systemic inflammation and disruption of synaptic vesicular transport.

PMID: 31640099 [PubMed - indexed for MEDLINE]

CRISPR based editing of SIV proviral DNA in ART treated non-human primates.

Recent Research Articles from UNTHSC - Sun, 11/29/2020 - 06:22
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CRISPR based editing of SIV proviral DNA in ART treated non-human primates.

Nat Commun. 2020 Nov 27;11(1):6065

Authors: Mancuso P, Chen C, Kaminski R, Gordon J, Liao S, Robinson JA, Smith MD, Liu H, Sariyer IK, Sariyer R, Peterson TA, Donadoni M, Williams JB, Siddiqui S, Bunnell BA, Ling B, MacLean AG, Burdo TH, Khalili K

Abstract
Elimination of HIV DNA from infected individuals remains a challenge in medicine. Here, we demonstrate that intravenous inoculation of SIV-infected macaques, a well-accepted non-human primate model of HIV infection, with adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing construct designed for eliminating proviral SIV DNA, leads to broad distribution of editing molecules and precise cleavage and removal of fragments of the integrated proviral DNA from the genome of infected blood cells and tissues known to be viral reservoirs including lymph nodes, spleen, bone marrow, and brain among others. Accordingly, AAV9-CRISPR treatment results in a reduction in the percent of proviral DNA in blood and tissues. These proof-of-concept observations offer a promising step toward the elimination of HIV reservoirs in the clinic.

PMID: 33247091 [PubMed - as supplied by publisher]

Knowledge, Attitudes, and Practices on Climate Change and Dengue in Lao People's Democratic Republic and Thailand.

Recent Research Articles from UNTHSC - Sat, 11/28/2020 - 07:39
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Knowledge, Attitudes, and Practices on Climate Change and Dengue in Lao People's Democratic Republic and Thailand.

Environ Res. 2020 Nov 24;:110509

Authors: Rahman MS, Overgaard HJ, Pientong C, Mayxay M, Ekalaksananan T, Aromseree S, Phanthanawiboon S, Zafar S, Shipin O, Paul RE, Phommachanh S, Pongvongsa T, Vannavong N, Haque U

Abstract
BACKGROUND: Dengue is linked with climate change in tropical and sub-tropical countries including the Lao People's Democratic Republic (Laos) and Thailand. Knowledge about these issues and preventive measures can affect the incidence and outbreak risk of dengue. Therefore, the present study was conducted to determine the knowledge, attitudes, and practices (KAP) among urban and rural communities and government officials about climate change and dengue in Laos and Thailand.
METHODS: A cross-sectional KAP survey about climate change and dengue were conducted in 360 households in Laos (180 urban and 180 rural), 359 households in Thailand (179 urban and 180 rural), and 20 government officials (10 in each country) using structured questionnaires. Data analysis was undertaken using descriptive methods, principal component analysis, Chi-square test or Fisher's exact test (as appropriate), and logistic regression.
RESULTS: Significant differences among the selected communities in both countries were found in terms of household participant's age, level of education, socioeconomic status, attitude level of climate change and KAP level of dengue (P < 0.05; 95% CI). Overall, participants' KAP about climate change and dengue were low except the attitude level for dengue in both countries. The level of awareness among government officials regarding the climatic relationship with dengue was also low. In Lao households, participants' knowledge about climate change and dengue was significantly associated with the level of education and socioeconomic status (SES) (P < 0.01). Their attitudes towards climate change and dengue were associated with educational level and internet use (P < 0.05). Householders' climate change related practices were associated with SES (P < 0.01) and dengue related practices were associated with educational level, SES, previous dengue experience and internet use (P < 0.01). In Thailand, participants' knowledge about climate change was associated with the level of education and SES (P < 0.01). Their attitudes towards climate change were associated with residence status (urban/rural) and internet use (P < 0.05); climate change related practices were associated with educational level and SES (P < 0.05). Dengue related knowledge of participants was associated with SES and previous dengue experience (P < 0.05); participants' dengue related attitudes and practices were associated with educational level (P < 0.01).
CONCLUSION: The findings call for urgently needed integrated awareness programs to increase KAP levels regarding climate change adaptation, mitigation and dengue prevention to improve the health and welfare of people in these two countries, and similar dengue-endemic countries.

PMID: 33245883 [PubMed - as supplied by publisher]

Rapid de novo evolution of lysis genes in single-stranded RNA phages.

Recent Research Articles from UNTHSC - Sat, 11/28/2020 - 07:39
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Rapid de novo evolution of lysis genes in single-stranded RNA phages.

Nat Commun. 2020 Nov 26;11(1):6009

Authors: Chamakura KR, Tran JS, O'Leary C, Lisciandro HG, Antillon SF, Garza KD, Tran E, Min L, Young R

Abstract
Leviviruses are bacteriophages with small single-stranded RNA genomes consisting of 3-4 genes, one of which (sgl) encodes a protein that induces the host to undergo autolysis and liberate progeny virions. Recent meta-transcriptomic studies have uncovered thousands of leviviral genomes, but most of these lack an annotated sgl, mainly due to the small size, lack of sequence similarity, and embedded nature of these genes. Here, we identify sgl genes in 244 leviviral genomes and functionally characterize them in Escherichia coli. We show that leviviruses readily evolve sgl genes and sometimes have more than one per genome. Moreover, these genes share little to no similarity with each other or to previously known sgl genes, thus representing a rich source for potential protein antibiotics.

PMID: 33243984 [PubMed - in process]

Use of Complementary Health Approaches for Chronic Low-Back Pain: A Pain Research Registry-Based Study.

Recent Research Articles from UNTHSC - Thu, 11/26/2020 - 07:04
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Use of Complementary Health Approaches for Chronic Low-Back Pain: A Pain Research Registry-Based Study.

J Altern Complement Med. 2020 May;26(5):369-375

Authors: Licciardone JC, Pandya V

Abstract
Objectives: To measure the use of complementary health approaches (CHAs) recommended in recent clinical practice guidelines relating to low-back pain, multivariate factors associated with their use, and clinical outcomes of CHA users and nonusers. Design: Observational cross-sectional study. Settings/Location: The Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation. Subjects: A total of 568 patients with chronic low-back pain. Interventions: Massage therapy, spinal manipulation, yoga, and acupuncture. Outcome measures: The numerical rating scale for low-back pain intensity, Roland-Morris Disability Questionnaire for back-related disability, and the Patient-Reported Outcomes Measurement Information System with 29 items for quality-of-life deficits relating to sleep disturbance, pain interference with activities, anxiety, depression, and low energy/fatigue. Results: The distribution of the number of different CHAs used by patients for low-back pain was as follows: 0, 179 (31.5%); 1, 139 (24.5%); 2, 160 (28.2%); 3, 70 (12.3%); and 4, 20 (3.5%). The numbers of patients using the specific CHAs were as follows: massage therapy, 271 (47.7%); spinal manipulation, 238 (41.9%); yoga, 144 (25.4%); and acupuncture, 96 (16.9%). Opioids had been used for low-back pain by 415 (73.1%) patients. Higher levels of education and higher pain self-efficacy scores were associated with greater use of any CHA, whereas increasing age and being Black were associated with lesser use of any CHA. Any CHA use was associated with lesser low-back pain intensity and lesser back-related disability. Patients who used massage therapy reported better clinical outcomes across all three dimensions. Patient pain self-efficacy also enhanced the effect of CHA use. Conclusions: The use of CHAs relative to opioids for low-back pain was inconsistent with recommendations from recent clinical practice guidelines despite clinical benefits with CHA use in this study. More research is needed on ways to improve the uptake of CHAs recommended for low-back pain, particularly among older and Black patients.

PMID: 32167785 [PubMed - indexed for MEDLINE]

Effect of implant formation on drug release kinetics of in situ forming implants.

Recent Research Articles from UNTHSC - Wed, 11/25/2020 - 07:37
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Effect of implant formation on drug release kinetics of in situ forming implants.

Int J Pharm. 2020 Nov 21;:120105

Authors: Sung Suh M, Kastellorizios M, Tipnis N, Zou Y, Wang Y, Choi S, Burgess DJ

Abstract
In situ forming implants are attractive long-acting implant dosage forms due to their: i) ability to control drug release; ii) simple manufacturing process; and iii) minimally invasive administration. In situ forming implants are typically made of a drug, solvent, and a biocompatible polymer that controls drug release. Once injected in the subcutaneous tissue, they form solid depots through solvent/non-solvent exchange and phase separation of the biodegradable polymer (such as poly (lactic-co-glycolic acid), PLGA and poly (lactic acid), PLA). However, the mechanism of implant formation and the changes in their microstructure that determine drug release behavior are not fully understood. Furthermore, there is no standardized in vitro release testing method for in situ forming implants due to limitations in recreating bio-relevant and reproducible implant formation in vitro with controllable implant shape, dimensions and surface-to-volume ratio. In the present study, bio-relevant implant formation was recreated in vitro by testing five different methods to determine their effect on drug release kinetics, reproducibility, and internal microstructure formation. The leuprolide acetate formulation Eligard® was used as a model in situ-forming implant, consisting of lyophilized leuprolide acetate, and PLGA dissolved in N-methyl pyrrolidone. The results revealed that the in vitro implant formation method is a crucial step in the dissolution testing process that significantly impacts the release profile of in situ forming implants. An implant formation method that utilizes dissolvable polyvinyl alcohol (PVA) films allowed for initial drug burst release control by modulating implant dimensions (i.e. surface area) and resulted in reproducible in vitro release profiles. In addition, implant formation was shown to affect the internal microstructure of in situ forming implant and was the main factor controlling the release profile which consisted of an initial release phase followed by a release plateau (lag phase) and then a second erosion-controlled release phase.

PMID: 33232755 [PubMed - as supplied by publisher]

Clinical Symptoms of Arboviruses in Mexico.

Recent Research Articles from UNTHSC - Wed, 11/25/2020 - 07:37
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Clinical Symptoms of Arboviruses in Mexico.

Pathogens. 2020 Nov 19;9(11):

Authors: Ananth S, Shrestha N, Treviño C JA, Nguyen US, Haque U, Angulo-Molina A, Lopez-Lemus UA, Lubinda J, Sharif RM, Zaki RA, Sánchez Casas RM, Cervantes D, Nandy R

Abstract
Arboviruses such as Chikungunya (CHIKV), Dengue (DENV), and Zika virus (ZIKV) have emerged as a significant public health concern in Mexico. The existing literature lacks evidence regarding the dispersion of arboviruses, thereby limiting public health policy's ability to integrate the diagnosis, management, and prevention. This study seeks to reveal the clinical symptoms of CHIK, DENV, and ZIKV by age group, region, sex, and time across Mexico. The confirmed cases of CHIKV, DENV, and ZIKV were compiled from January 2012 to March 2020. Demographic characteristics analyzed significant clinical symptoms of confirmed cases. Multinomial logistic regression was used to assess the association between clinical symptoms and geographical regions. Females and individuals aged 15 and older had higher rates of reported significant symptoms across all three arboviruses. DENV showed a temporal variation of symptoms by regions 3 and 5, whereas ZIKV presented temporal variables in regions 2 and 4. This study revealed unique and overlapping symptoms between CHIKV, DENV, and ZIKV. However, the differentiation of CHIKV, DENV, and ZIKV is difficult, and diagnostic facilities are not available in rural areas. There is a need for adequately trained healthcare staff alongside well-equipped lab facilities, including hematological tests and imaging facilities.

PMID: 33228120 [PubMed]

Possible Protective Effect of Omalizumab on Lung Function Decline in Patients Experiencing Asthma Exacerbations.

Recent Research Articles from UNTHSC - Tue, 11/24/2020 - 06:09
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Possible Protective Effect of Omalizumab on Lung Function Decline in Patients Experiencing Asthma Exacerbations.

J Allergy Clin Immunol Pract. 2020 Oct 24;:

Authors: Busse WW, Szefler SJ, Haselkorn T, Iqbal A, Ortiz B, Lanier BQ, Chipps BE

Abstract
BACKGROUND: Frequent exacerbations are associated with greater FEV1 decline in patients with asthma. The effect of omalizumab versus placebo on lung function in patients experiencing asthma exacerbations has not been previously examined.
OBJECTIVE: To evaluate the relationship between postbaseline (treatment phase) exacerbation status and lung function decline in children, adolescents, and adults treated with omalizumab versus placebo using data from 3 pediatric and adolescent/adult studies.
METHODS: Changes in percent predicted FEV1 (ppFEV1) and FEV1 by treatment (omalizumab/placebo) and postbaseline exacerbation status (exacerbators/nonexacerbators) were assessed in patients aged 6 to 11 years (IA05, n = 576) and 12 to 75 years (EXTRA/INNOVATE pooled, n = 1202). Pediatric patients were examined at treatment weeks 12, 24, 28, 40, and 52, and adolescent/adult data at weeks 4, 12, 20, and 28.
RESULTS: Omalizumab-treated patients experienced larger increases in ppFEV1 and FEV1 compared with placebo-treated patients in the pediatric and pooled adolescent/adult populations. The response was observed in pediatric exacerbators, with significantly larger increases in ppFEV1 and FEV1 at week 12 (mean difference [95% CI], 4.11% [0.93%-7.30%], P = .011 for ppFEV1; 80 [10-140] mL, P = .017 for FEV1) and week 28 (mean difference [95% CI], 3.65% [0.11%-7.19%], P = .043 for ppFEV1; 100 [30-170] mL, P = .007 for FEV1). In the adolescent/adult population, both exacerbators and nonexacerbators derived similar benefit with omalizumab compared with placebo.
CONCLUSIONS: Findings from this post hoc analysis suggest that omalizumab may confer some protection against lung function decline among patients who experienced exacerbations during treatment.

PMID: 33223095 [PubMed - as supplied by publisher]

Characterization of Tear Immunoglobulins in a Small-Cohort of Keratoconus Patients.

Recent Research Articles from UNTHSC - Tue, 11/24/2020 - 06:09
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Characterization of Tear Immunoglobulins in a Small-Cohort of Keratoconus Patients.

Sci Rep. 2020 06 10;10(1):9426

Authors: McKay TB, Serjersen H, Hjortdal J, Zieske JD, Karamichos D

Abstract
Keratoconus (KC) is classically considered a non-inflammatory condition caused by central corneal thinning that leads to astigmatism and reduced visual acuity. Previous studies have identified increased systemic levels of pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-9, suggesting that KC may have an inflammatory component in at least a subset of patients. In this study, we evaluated the levels of different immunoglobulins (light and heavy chains) based on Ig α, Ig λ, Ig κ, Ig µ, and Ig heavy chain subunits in non-KC tears (n = 7 control individuals) and KC tears (n = 7 KC patients) using tandem-liquid chromatography mass spectrometry. The most abundant Ig heavy chains detected in both control individuals and KC patients were Ig α-1 and Ig α-2 likely correlating to the higher IgA levels reported in human tears. We identified significant differences in immunoglobulin κ-chain V-II levels in KC patients compared to control individuals with no significant difference in Ig κ/Ig λ ratios or heavy chain levels. Our study supports previous findings suggesting that KC possesses a systemic component that may contribute to the KC pathology. Further studies are required to define causality and establish a role for systemic immune system-dependent factors and pro-inflammatory processes in KC development or progression.

PMID: 32523038 [PubMed - indexed for MEDLINE]

Distinct Roles of mTOR Targets S6K1 and S6K2 in Breast Cancer.

Recent Research Articles from UNTHSC - Sat, 11/21/2020 - 05:56
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Distinct Roles of mTOR Targets S6K1 and S6K2 in Breast Cancer.

Int J Mol Sci. 2020 Feb 11;21(4):

Authors: Sridharan S, Basu A

Abstract
The mechanistic target of rapamycin (mTOR) is a master regulator of protein translation, metabolism, cell growth and proliferation. It forms two complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2). mTORC1 is frequently deregulated in many cancers, including breast cancer, and is an important target for cancer therapy. The immunosuppressant drug rapamycin and its analogs that inhibit mTOR are currently being evaluated for their potential as anti-cancer agents, albeit with limited efficacy. mTORC1 mediates its function via its downstream targets 40S ribosomal S6 kinases (S6K) and eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). There are two homologs of S6K: S6K1 and S6K2. Most of the earlier studies focused on S6K1 rather than S6K2. Because of their high degree of structural homology, it was generally believed that they behave similarly. Recent studies suggest that while they may share some functions, they may also exhibit distinct or even opposite functions. Both homologs have been implicated in breast cancer, although how they contribute to breast cancer may differ. The purpose of this review article is to compare and contrast the expression, structure, regulation and function of these two S6K homologs in breast cancer.

PMID: 32054043 [PubMed - indexed for MEDLINE]

A Comparison of Protocols for Simulating Hemorrhage in Humans: Step vs. Ramp Lower Body Negative Pressure.

Recent Research Articles from UNTHSC - Fri, 11/20/2020 - 08:16
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A Comparison of Protocols for Simulating Hemorrhage in Humans: Step vs. Ramp Lower Body Negative Pressure.

J Appl Physiol (1985). 2020 Nov 19;:

Authors: Rosenberg AJ, Kay VL, Anderson GK, Sprick JD, Rickards CA

Abstract
Lower body negative pressure (LBNP) elicits central hypovolemia, and has been used to simulate the cardiovascular and cerebrovascular responses to hemorrhage in humans. LBNP protocols commonly employ progressive stepwise reductions in chamber pressure for specific time periods. However, continuous ramp LBNP protocols have also been utilized to simulate the continuous nature of most bleeding injuries. The aim of this study was to compare tolerance and hemodynamic responses between these two LBNP profiles. Healthy human subjects (N=19; age, 27±4 y; 7F/12M) completed a 1) step LBNP protocol (5-min steps), and; 2) continuous ramp LBNP protocol (3 mmHg/min), both to presyncope. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), middle and posterior cerebral artery velocity (MCAv and PCAv), cerebral oxygen saturation (ScO2), and end-tidal CO2 (etCO2) were measured. LBNP tolerance, via the cumulative stress index (CSI, summation of chamber pressure*time at each pressure), and hemodynamic responses were compared between the two protocols. The CSI (Step: 911±97 mmHg*min vs. Ramp: 823±83 mmHg*min; P=0.12) and the magnitude of central hypovolemia (%Δ SV, Step: -54.6±2.6 % vs. Ramp: -52.1±2.8 %; P=0.32) were similar between protocols. While there were no differences between protocols for the maximal %Δ HR (P=0.88), the %Δ MAP during the step protocol was attenuated (P=0.05), and the reductions in MCAv, PCAv, ScO2,and etCO2 were greater (P≤0.08) when compared with the ramp protocol at presyncope. These results indicate that when comparing cardiovascular responses to LBNP across different laboratories, the specific pressure profile must be considered as a potential confounding factor.

PMID: 33211600 [PubMed - as supplied by publisher]

Improvements in Retention in Care and HIV Viral Suppression Among Persons with HIV and Comorbid Mental Health Conditions: Patient-Centered HIV Care Model.

Recent Research Articles from UNTHSC - Fri, 11/20/2020 - 08:16
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Improvements in Retention in Care and HIV Viral Suppression Among Persons with HIV and Comorbid Mental Health Conditions: Patient-Centered HIV Care Model.

AIDS Behav. 2020 Dec;24(12):3522-3532

Authors: Byrd KK, Hardnett F, Hou JG, Clay PG, Suzuki S, Camp NM, Shankle MD, Weidle PJ, Taitel MS, Patient-Centered HIV Care Model Team

Abstract
The Patient-centered HIV Care Model (PCHCM) integrated community-based pharmacists with medical providers and required sharing of patient clinical information and collaborative therapy-related action planning. We determined the proportions of participants with HIV and mental health conditions who were retained in care and the proportion virally suppressed, pre- and post-implementation. Overall, we found a relative 13% improvement in both retention [60% to 68% (p = 0.009)] and viral suppression [79% to 90% (p < 0.001)]. Notable improvements were seen among persons triply diagnosed with HIV, mental illness and substance use [+ 36% (50% to 68%, p = 0.036) and + 32% (66% to 86%, p = 0.001) in retention and viral suppression, respectively]. There were no differences in the proportions of persons adherent to psychiatric medications, pre- to post-implementation, nor were there differences in the proportions of persons retained in care or virally suppressed by psychiatric medication adherence, post-implementation. PCHCM demonstrated that collaborations between community-based pharmacists and medical providers can improve HIV care continuum outcomes among persons with mental health conditions.

PMID: 32415615 [PubMed - indexed for MEDLINE]

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