Background::Hypertension (HTN) involves genetic variability in the renin-angiotensin system and influences antihypertensive response. We previously reported that angiotensinogen ( AGT) messenger RNA (mRNA) is endogenously bound by miR-122-5p and rs699 A > G decreases reporter mRNA in the microRNA functional-assay PASSPORT-seq. The AGT promoter variant rs5051 C > T is in linkage disequilibrium (LD) with rs699 A > G and increases AGT transcription. The independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C > T counterbalances AGT decreased by rs699 A > G, and when these variants occur independently, it translates to HTN-related phenotypes. Methods::We used in silico, in vitro, in vivo, and retrospective models to test this hypothesis.Results::In silico, rs699 A > G is predicted to increase miR-122-5p binding affinity by 3%. Mir-eCLIP results show rs699 is 40-45 nucleotides from the strongest microRNA-binding site in the AGT mRNA. Unexpectedly, rs699 A > G increases AGT mRNA in an AGT-plasmid-cDNA HepG2 expression model. Genotype-Tissue Expression (GTEx) and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A > G occurs independently from rs5051 C > T. However, GTEx and the in vitro experiments suggest rs699 A > G confers cell-type-specific effects on AGT mRNA abundance, and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A > G associations with HTN. Conclusions::We found that rs5051 C > T and rs699 A > G significantly associate with systolic blood pressure in Black participants in the UK Biobank, demonstrating a fourfold larger effect than in White participants. Further studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C > T or rs699 A > G. Studies like this will help clinicians move beyond the use of race as a surrogate for genotype.

Background::Hypertension (HTN) involves genetic variability in the renin-angiotensin system and influences antihypertensive response. We previously reported that angiotensinogen ( AGT) messenger RNA (mRNA) is endogenously bound by miR-122-5p and rs699 A > G decreases reporter mRNA in the microRNA functional-assay PASSPORT-seq. The AGT promoter variant rs5051 C > T is in linkage disequilibrium (LD) with rs699 A > G and increases AGT transcription. The independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C > T counterbalances AGT decreased by rs699 A > G, and when these variants occur independently, it translates to HTN-related phenotypes. Methods::We used in silico, in vitro, in vivo, and retrospective models to test this hypothesis.Results::In silico, rs699 A > G is predicted to increase miR-122-5p binding affinity by 3%. Mir-eCLIP results show rs699 is 40-45 nucleotides from the strongest microRNA-binding site in the AGT mRNA. Unexpectedly, rs699 A > G increases AGT mRNA in an AGT-plasmid-cDNA HepG2 expression model. Genotype-Tissue Expression (GTEx) and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A > G occurs independently from rs5051 C > T. However, GTEx and the in vitro experiments suggest rs699 A > G confers cell-type-specific effects on AGT mRNA abundance, and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A > G associations with HTN. Conclusions::We found that rs5051 C > T and rs699 A > G significantly associate with systolic blood pressure in Black participants in the UK Biobank, demonstrating a fourfold larger effect than in White participants. Further studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C > T or rs699 A > G. Studies like this will help clinicians move beyond the use of race as a surrogate for genotype.

BACKGROUND: The Clinic for the Therapy Services (CTS) has considered reverting to face-to-face service delivery due to the downward trend in COVID-19 cases in the Philippines. However, the clinic has yet to investigate the willingness of the clients to this mode as a basis for its effective implementation. OBJECTIVES: The study described the readiness of CTS clients in returning to face-to-face therapy amidst the pandemic. It also discussed the factors affecting readiness based on a survey. METHODOLOGY: Fifty-five screened survey responses on the readiness of clients in returning to face-to-face therapy were gathered from January 30 to February 28, 2021. These underwent retrospective data analysis. Eight prospective online key informant interviews were conducted for clarifications in May 2022. This study utilized a descriptive analysis of quantitative categorical variables and a thematic content analysis of qualitative data. RESULTS: The majority of the respondents (35) stated readiness to attend face-to-face therapy followed by those who answered “No” (11), “Maybe” (5), and others (4). Factors that may have affected readiness included travel, characteristics of face-to-face therapy, health conditions, vaccine, and COVID-19 concerns. Frequently preferred health and safety strategies were the provision of hygiene products, disinfection, limited people inside the clinic, separate therapy areas, and ventilation. CONCLUSION Most of the respondents expressed willingness to receive face-to-face therapy in April or May of 2021. Feasibility of travel and decreased number of COVID-19 cases may have encouraged willingness to attend. Those who were hesitant reported concerns with traveling, characteristics of face-to-face therapy, health conditions, the COVID-19 situation, and the vaccine.
rehabilitation ; COVID-19

Parenteral nutrition-associated liver disease (PNALD) is a liver dysfunction caused by various risk factors presented in patients receiving total parenteral nutrition (TPN). Omega-6 rich Intralipid® and omega-3 rich Omegaven® are two intravenous lipid emulsions used in TPN. TPN could affect the hepatic expression of genes in anti-oxidative stress, but it's unknown whether TPN affects genes in drug metabolism. In this study, either Intralipid®- or Omegaven®-based TPN was administered to mice and the expression of a cohort of genes involved in anti-oxidative stress or drug metabolism was analyzed, glutathione (GSH) levels were measured, and protein levels for two key drug metabolism genes were determined. Overall, the expression of most genes was downregulated by Intralipid®-based TPN ( and ). Omegaven® showed similar results as Intralipid® except for preserving the expression of and and increasing . Total GSH levels were decreased by Intralipid®, but increased by Omegaven®. CYP3A11 protein levels were increased by Omegaven®. In conclusion, TPN reduced the expression of many genes involved in anti-oxidative stress and drug metabolism in mice. However, Omegaven® preserved expression of , suggesting another beneficial effect of Omegaven® in protecting liver functions.

Background & Objective: Endovascular treatment is the widely accepted treatment for patients with anterior circulation stroke within 6 hours of onset of stroke. We aimed to evaluate the advantages of endovascular treatment compared to standard medical treatment in treating patients with anterior circulation stroke beyond the 6-hour therapeutic window. Methods: We reviewed the literature concerning endovascular treatment versus medical treatment beyond the 6-hour therapeutic window. Using random-effects meta-analysis, we evaluated the following outcomes: modified Rankin scale in the three-month follow-up [excellent outcome (mRS≤1), functional independence (mRS≤2), moderate outcome(mRS≤3)], recanalization rate at 24 hours, mortality at 90 days or in-hospital, symptomatic intracranial hemorrhage, parenchymal hematoma type 2 and hemorrhagic infarction 1. Results: Four studies including 642 patients were evaluated. Endovascular treatment was associated with higher odds of excellent outcome (OR 2.55; 95% CI 1.48 to 4.41,), functional independence (OR 3.64; 95% CI 2.43 to 5.45), moderate outcome (OR 2.70; 95% CI 1.95-3.74) and recanalization rate at 24 hours (OR 8.81; 95%CI 2.81 to 27.69) compared to MT. No difference in the rates of mortality, symptomatic intracranial hemorrhage, parenchymal hematoma type 2 or hemorrhagic infarction 1 was found between the 2 groups. Studies using strict perfusion imaging inclusion selection showed better moderate outcome in comparison to the studies without perfusion imaging inclusion selection (P <0.012). Conclusion: Our study highlights the superiority of endovascular treatment over standard medical treatment alone for treating patients with anterior circulation stroke beyond 6 hours since stroke onset, although more studies are required for further investigation. Standard of strict selection for eligible patients before endovascular treatment should be based on DAWN or DEFFUSE 3 inclusion criteria.

Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis. In this study, we prepared multifunctional microspheres loading I-labeled hollow copper sulfide nanoparticles and paclitaxel (I-HCuSNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats. F-fluordeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) imaging detected that the expansion of the tumor volume was delayed (<0.05) following intra-tumoral (i.t.) injection with I-HCuSNPs-MS-PTX plus near-infrared (NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography (SPECT)/photoacoustic imaging mediated by I-HCuSNPs-MS-PTX demonstrated that microspheres were mainly distributed in the tumors with a relatively low distribution in other organs. Our results revealed that I-HCuSNPs-MS-PTX offered combined photothermal, chemo- and radio-therapies, eliminating tumors at a relatively low dose, as well as allowing SPECT/CT and photoacoustic imaging monitoring of distribution of the injected agents non-invasively. The copper sulfide-loaded microspheres, I-HCuSNPs-MS-PTX, can serve as a versatile theranostic agent in an orthotopic breast cancer model.

Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.

OBJECTIVES: Spiral ganglion neurons (SGNs) include potential endogenous progenitor populations for the regeneration of the peripheral auditory system. However, whether these populations are present in adult mice is largely unknown. We examined the presence and characteristics of SGN-neural stem cells (NSCs) in mice as a function of age. METHODS: The expression of Nestin and Ki67 was examined in sequentially dissected cochlear modiolar tissues from mice of different ages (from postnatal day to 24 weeks) and the sphere-forming populations from the SGNs were isolated and differentiated into different cell types. RESULTS: There were significant decreases in Nestin and Ki67 double-positive mitotic progenitor cells in vivo with increasing mouse age. The SGNs formed spheres exhibiting self-renewing activity and multipotent capacity, which were seen in NSCs and were capable of differentiating into neuron and glial cell types. The SGN spheres derived from mice at an early age (postnatal day or 2 weeks) contained more mitotic stem cells than those from mice at a late age. CONCLUSION: Our findings showed the presence of self-renewing and proliferative subtypes of SGN-NSCs which might serve as a promising source for the regeneration of auditory neurons even in adult mice.
Adult ; Animals ; Cochlea ; Deafness ; Hearing Loss ; Humans ; In Vitro Techniques* ; Mice* ; Nestin ; Neural Stem Cells* ; Neuroglia ; Neurons ; Regeneration ; Spiral Ganglion* ; Stem Cells

BACKGROUND AND PURPOSE: Interventions to reduce the risk for cerebrovascular events (CVE; stroke and transient ischemic attack [TIA]) after radiotherapy (RT) for head and neck cancer (HNCA) are needed. Among broad populations, statins reduce CVEs; however, whether statins reduce CVEs after RT for HNCA is unclear. Therefore, we aimed to test whether incidental statin use at the time of RT is associated with a lower rate of CVEs after RT for HNCA. METHODS: From an institutional database we identified all consecutive subjects treated with neck RT from 2002 to 2012 for HNCA. Data collection and event adjudication was performed by blinded teams. The primary outcome was a composite of ischemic stroke and TIA. The secondary outcome was ischemic stroke. The association between statin use and events was determined using Cox proportional hazard models after adjustment for traditional and RT-specific risk factors. RESULTS: The final cohort consisted of 1,011 patients (59±13 years, 30% female, 44% hypertension) with 288 (28%) on statins. Over a median follow-up of 3.4 years (interquartile range, 0.1 to 14) there were 102 CVEs (89 ischemic strokes and 13 TIAs) with 17 in statin users versus 85 in nonstatins users. In a multivariable model containing known predictors of CVE, statins were associated with a reduction in the combination of stroke and TIA (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2 to 0.8; P=0.01) and ischemic stroke alone (HR, 0.4; 95% CI, 0.2 to 0.8; P=0.01). CONCLUSIONS: Incidental statin use at the time of RT for HNCA is associated with a lower risk of stroke or TIA.
Cohort Studies ; Data Collection ; Female ; Follow-Up Studies ; Head and Neck Neoplasms ; Head ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Ischemic Attack, Transient ; Neck ; Proportional Hazards Models ; Radiotherapy ; Risk Factors ; Stroke