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Heparan sulfate 3-O-sulfotransferase 4 is genetically associated with herpes zoster and enhances varicella-zoster virus-mediated fusogenic activity

Mol Pain. 2021 Jan-Dec;17:17448069211052171. doi: 10.1177/17448069211052171.

ABSTRACT

Acute pain that is associated with herpes zoster (HZ) can become long-lasting neuropathic pain, known as chronic post-herpetic neuralgia (PHN), especially in the elderly. HZ is caused by the reactivation of latent varicella-zoster virus (VZV), whereas PHN is not attributed to ongoing viral replication. Although VZV infection reportedly induces neuronal cell fusion in humans, the pathogenesis of PHN is not fully understood. A genome-wide association study (GWAS) revealed significant associations between PHN and the rs12596324 single-nucleotide polymorphism (SNP) of the heparan sulfate 3-O-sulfotransferase 4 (HS3ST4) gene in a previous study. To further examine whether this SNP is associated with both PHN and VZV reactivation, associations between rs12596324 and a history of HZ were statistically analyzed using GWAS data. HZ was significantly associated with the rs12596324 SNP of HS3ST4, indicating that HS3ST4 is related to viral replication. We investigated the influence of HS3ST4 expression on VZV infection in cultured cells. Fusogenic activity after VZV infection was enhanced in cells with HS3ST4 expression by microscopy. To quantitatively evaluate the fusogenic activity, we applied cytotoxicity assay and revealed that HS3ST4 expression enhanced cytotoxicity after VZV infection. Expression of the VZV glycoproteins gB, gH, and gL significantly increased cytotoxicity in cells with HS3ST4 expression by cytotoxicity assay, consistent with the fusogenic activity as visualized by fluorescence microscopy. HS3ST4 had little influence on viral genome replication, revealed by quantitative real-time polymerase chain reaction. These results suggest that HS3ST4 enhances cytotoxicity including fusogenic activity in the presence of VZV glycoproteins without enhancing viral genome replication.

PMID:34904858 | DOI:10.1177/17448069211052171

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A new perspective on the pleiotropic blood pressure improvement effect of sitagliptin: downregulation of miRNA-155 and miRNA-21

Bratisl Lek Listy. 2021;122(12):892-899. doi: 10.4149/BLL_2021_145.

ABSTRACT

INTRODUCTION: Deterioration of vascular responses is the crucial event in the initiation of cardiovascular problems in hypertension (HT) and diabetes mellitus (DM). A well-known oral antidiabetic, sitagliptin, has pleiotropic effects besides improving glycemic state in type-2 DM. This study aimed to investigate the therapeutic effect of sitagliptin on blood pressure with previously unassessed parameters of well-known pathophysiological processes and especially at the microRNA (miRNA) level where there are many unknowns.

METHODS: N-nitro-L-arginine methyl ester (L-NAME)-induced HT model was performed on nondiabetic male rats. Four groups (including 7 rats in each) were formed: normotensives, sitagliptin-treated, HT and sitagliptin-treated HT. Asymmetric dimethylarginine (ADMA), intercellular adhesion molecule-1 (ICAM-1) and tyrosine hydroxylase (TH), HT related miRNAs were evaluated. In-vitro vessel responses were observed.

RESULTS: L-NAME led to a significant increase in blood pressure. Hypertensives exhibited significantly increased contractile responses, consistent with increased ADMA, ICAM-1. Sitagliptin decreased TH levels but not statistically significantly. The new side of the study was the miRNA-21 and miRNA-155 expressions were in line with other parameters in both the HT and sitagliptin-treated HT groups.

CONCLUSION: Sitagliptin may control comorbidities, especially HT and introduces new targets to alleviate vascular responses. The new knowledge is; sitagliptin may show these effects through microRNAs (Tab. 2, Fig. 6, Ref. 46).

PMID:34904852 | DOI:10.4149/BLL_2021_145

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Can neutrophil-to-lymphocyte, platelet-to-lymphocyte and monocyte-to-lymphocyte ratios be useful to the diagnosis of aseptic loosening after total knee arthroplasty?

Bratisl Lek Listy. 2021;122(12):880-883. doi: 10.4149/BLL_2021_143.

ABSTRACT

BACKGROUND: The aim of this study is to determine the role of hematological parameters – neutrophil/lymphocyte, platelet/lymphocyte, and monocyte/lymphocyte ratios – in the diagnosis of aseptic loosening after total knee arthroplasty.

METHODS: This study retrospectively analyzed the data of 244 patients who had primary total knee arthroplasty and 66 patients with aseptic loosening developed after total knee arthroplasty. The white blood cell counts, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, monocyte/lymphocyte ratio and c-reactive protein levels in both groups were determined using the results of venous blood samples collected during preoperative preparation and compared between the groups.

RESULTS: Our study findings reveal that the monocyte/lymphocyte ratio of the group with aseptic loosening was statistically significantly different from that of the patient group who had primary total knee arthroplasty (p=0.02). Furthermore, although c-reactive protein levels are not high enough to suggest systemic inflammation, the difference between the groups is statistically significant (p=0.01).

CONCLUSIONS: No hematological parameter that could be used in the diagnosis of aseptic loosening has been defined in the literature so far. This study demonstrated that the monocyte/lymphocyte ratio could be a helpful parameter in the diagnosis of aseptic loosening (Tab. 1, Fig. 1, Ref. 28).

PMID:34904850 | DOI:10.4149/BLL_2021_143

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COVID-19 symptom duration predicts immunoglobulin G seropositivity

Bratisl Lek Listy. 2021;122(12):861-865. doi: 10.4149/BLL_2021_139.

ABSTRACT

OBJECTIVES: The study focused on the relationship between routine clinical characteristics and anti-SARS-CoV-2 specific antibodies in a pilot sample of healthcare workers (HCWs) having suffered COVID-19. The aim was to investigate the existence of readily available predictors of antibodies against COVID-19.

METHODS: As part of the recognition of COVID-19 as an occupational disease in 152 HCWs with the mean age of 43.2 years, personal, anthropometric and anamnestic data related to the disease as well as anti-spike immunoglobulin (Ig) levels were obtained. Through descriptive statistics, correlation and regression analyses, relationships of all variables and Ig levels, especially seropositivity of IgG, were investigated.

RESULTS: The mean interval between the symptom onset and the determination of antibodies was 58 days. IgG seropositivity and IgM seropositivity were noted in 82 % and 49 % of HCWs, respectively. Symptom duration was the only statistically significant predictor of IgG seropositivity. With each day of symptom duration, the probability of IgG seropositivity increased from 1.078 to 1.092 times (p < 0.05). If symptoms lasted longer than 17 days, a majority (almost 80 %) of the subjects demonstrated seropositivity in the following months. CONCLUSION: The presence of IgG immunity may be assumed from symptom duration. Such easy recognizing of seropositive patients may be a useful tool, e.g. in vaccination strategies (Tab. 3, Fig. 1, Ref. 28).

PMID:34904847 | DOI:10.4149/BLL_2021_139

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Stereotactic Body Radiotherapy in Oligomestatic/Oligoprogressive Sarcoma: Safety and Effectiveness Beyond Intrinsic Radiosensitivity

Cancer J. 2021 Nov-Dec 01;27(6):423-427. doi: 10.1097/PPO.0000000000000551.

ABSTRACT

BACKGROUND: Metastatic soft tissue sarcoma (STS) patients may benefit from local ablative treatments due to modest efficacy of systemic chemotherapy. However, use of stereotactic body radiotherapy (SBRT) is controversial because of presumed radioresistance of STS.

METHODS: Patients treated with SBRT for oligometastatic and oligoprogressive metastatic STS were retrospectively reviewed to assess results in terms of local control (LC), disease-free survival (DFS), and overall survival (OS). Incidence and grade of adverse events were reported. Statistical analysis was performed to identify variables correlated with outcome and toxicity.

RESULTS: Forty patients were treated with SBRT to a median biologic effective dose (BED) of 105 (66-305) Gy5 to 77 metastases. Two-year LC, DFS, and OS were 67%, 23%, and 40%. Improved LC was shown in patients receiving a BED >150 Gy5 (hazard ratio [HR], 3.9; 95% confidence interval [CI], 1.6-9.7; P = 0.028). A delay >24 months between primary tumor diagnosis and onset of metastases was associated with improved DFS (HR, 0.46; 95% CI, 0.22-0.96; P = 0.01) and OS (HR, 0.48; 95% CI, 0.23-0.99; P = 0.03). No toxicity grade ≥3 was observed.

CONCLUSIONS: Stereotactic body radiotherapy is effective in metastatic STS with a benign toxicity profile. A BED >150 Gy5 is required to maximize tumor control rates. Metastatic relapse >24 months after diagnosis is correlated to improved survival.

PMID:34904803 | DOI:10.1097/PPO.0000000000000551

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Effectiveness of technology-based interventions on psychological morbidities, quality of life for informal caregivers of stroke survivors: A systematic review and meta-analysis

J Adv Nurs. 2021 Dec 13. doi: 10.1111/jan.15130. Online ahead of print.

ABSTRACT

AIMS: To evaluate the effectiveness of technology-based interventions in reducing psychological morbidities such as depressive symptomology, anxiety, burden and improving quality of life and self-efficacy in informal caregivers of stroke survivors.

DESIGN: A systematic review and meta-analysis.

DATA SOURCES: An extensive search was systematically undertaken at CENTRAL, PubMed, Embase, Scopus, CINHAL, Web of Science and PsycInfo until January 2021. Grey literature and dissertations were searched in Google Scholar, ProQuest & Scholarbank@NUS. Studies involving registered trials were retrieved from Clinicaltrials.gov and CENTRAL, respectively.

REVIEW METHODS: Two reviewers independently screened the trials, conducted quality appraisal and extracted the data. Quality of the studies included in the review was assessed using Cochrane Risk of bias tool. Meta-analysis was conducted using RevMan 5.4. Narrative synthesis was performed for studies where results could not be pooled statistically. The results were reported abiding Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

RESULTS: This review included 15 trials with a total of 1276 informal caregivers of stroke survivors. Eleven trials were included in the meta-analysis. Subgroup analyses revealed that technology-based interventions with structured educational programs were statistically significant in reducing depressive symptoms (d = -0.27, 95% CI [-0.49 to -0.05], p = .02). Technology-based interventions with structured educational programs <3-month revealed significant effects (d = -0.31, 95% CI [-0.49 to -0.13], p = .0009). Results of narrative synthesis reported technology-based intervention with face-to-face training minimized depressive symptoms of informal caregivers. Notably, there were no statistically significant effects on anxiety, burden, quality of life and self-efficacy outcomes.

CONCLUSION: Technology-based interventions had beneficial effects in alleviating depressive symptoms among informal caregivers.

IMPACT: Technology-based interventions serve as a support mechanism for informal caregivers of stroke survivors who face time-constrains. Further high-quality randomized controlled trials are warranted to elucidate sustainability, optimal format and dosage of intervention.

PMID:34904746 | DOI:10.1111/jan.15130

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Skin Color Match in Head and Neck Reconstructive Surgery

Laryngoscope. 2021 Dec 14. doi: 10.1002/lary.29959. Online ahead of print.

ABSTRACT

OBJECTIVES/HYPOTHESIS: To quantify the degree of color match achieved during microvascular facial reconstruction, and to describe a novel technique for improving reconstructive skin color match. We hypothesize that split-thickness skin grafts (STSG) placed atop de-epithelialized free tissue produces better facial skin color match than free tissue with intact epithelium.

STUDY DESIGN: Cross sectional photographic study of reconstructed facial skin color match.

METHODS: Sixty-eight adults, who underwent head and neck reconstructive surgery, were divided into six categories based on cutaneous reconstructive technique: cervicofacial flap, radial forearm free flap (RFFF), fibula free flap, anterolateral thigh free flap (ALT), STSG over adiopofascial flap (STAFF), and STSG over myogenous flap (STMF). Averaged color samplings of the reconstructed defect and adjacent normal skin were taken from digital photographs. The color difference was calculated using the delta-E calculation. Blinded expert observers also rated the degree of color match. Nonparametric cohort contrast and correlation statistical analyses were performed.

RESULTS: The mean delta-E’s and 10-point Likert ratings for the ALT, fibula, RFFF, STAFF, STMF, and cervicofacial flaps were 11.6, 10.0, 7.7, 6.3, 8.8, and 4.7, and 5.1, 6.4, 2.4, 3.2, 2.7, and 1.1, respectively. Likert scale inter-rater correlation was strong, with coefficient = 0.80.

CONCLUSIONS: On average, STSG over de-epithelialized myogenous and adipofascial free tissue transfers produced a better color match than the skin paddles of donor sites, with the exception of the radial forearm donor site. Delta-E values obtained from photos correlated well with expert ratings of color match. This reliable technique for quantifying color match may be used in future studies.

LEVEL OF EVIDENCE: 3 Laryngoscope, 2021.

PMID:34904721 | DOI:10.1002/lary.29959

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A prospective comparison of costs between robotics, laparoscopy, and laparotomy in endometrial cancer among women with Class III obesity or higher

J Surg Oncol. 2021 Dec 14. doi: 10.1002/jso.26769. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: To compare the immediate operating room (OR), inpatient, and overall costs between three surgical modalities among women with endometrial cancer (EC) and Class III obesity or higher.

METHODS: A multicentre prospective observational study examined outcomes of women, with early stage EC, treated surgically. Resource use was collected for OR costs including OR time, equipment, and inpatient costs. Median OR, inpatient, and overall costs across surgical modalities were analyzed using an Independent-Samples Kruskal-Wallis Test among patients with BMI ≥ 40.

RESULTS: Out of 520 women, 103 had a BMI ≥ 40. Among women with BMI ≥ 40: median OR costs were $4197.02 for laparotomy, $5524.63 for non-robotic assisted laparoscopy, and $7225.16 for robotic-assisted laparoscopy (p < 0.001) and median inpatient costs were $5584.28 for laparotomy, $3042.07 for non-robotic assisted laparoscopy, and $1794.51 for robotic-assisted laparoscopy (p < 0.001). There were no statistically significant differences in the median overall costs: $10 291.50 for laparotomy, $8412.63 for non-robotic assisted laparoscopy, and $9002.48 for robotic-assisted laparoscopy (p = 0.185).

CONCLUSION: There was no difference in overall costs between the three surgical modalities in patient with BMI ≥ 40. Given the similar costs, any form of minimally invasive surgery should be promoted in this population.

PMID:34904716 | DOI:10.1002/jso.26769

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System intervention in community pharmacy setting: Leading to better patient care through reducing harm associated with coprescribing benzodiazepines and opioids

J Opioid Manag. 2021 Nov-Dec;17(6):445-453. doi: 10.5055/jom.2021.0679.

ABSTRACT

OBJECTIVE: The opioid epidemic is frequently discussed including the staggering numbers involved with coprescribing opioids and benzodiazepines associated with death. Community pharmacists, with the help of a system intervention, have a unique opportunity to help reduce the coprescribing of benzodiazepines and opioids and reduce the associated risk of death.

DESIGN: A single center retrospective chart review was conducted after a system intervention was placed, as a quality improvement project, from November 2019 to May 2020.

SETTING: Independent community pharmacy.

PATIENTS/PARTICIPANTS: Data included demographics, dosing of each medication pre- and post-intervention, and naloxone status. Main outcome(s) measures: The primary outcome evaluated was reduction in dose/discontinuation of these prescriptions. The secondary outcome evaluated was the number of naloxone prescriptions ordered per protocol and picked up.

RESULTS: The primary outcome did not show statistical difference; however, the secondary outcomes showed statistical significance.

CONCLUSION: In conclusion, community pharmacists, with the help of evolving technologies, can reduce harm associated with the coprescribing of benzodiazepines and opioids.

PMID:34904693 | DOI:10.5055/jom.2021.0679

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Flight activity and age cause wing damage in house flies

J Exp Biol. 2021 Dec 14:jeb.242872. doi: 10.1242/jeb.242872. Online ahead of print.

ABSTRACT

Wing damage attenuates aerial performance in many flying animals such as birds, bats and insects. Especially insect wings are fragile and light in order to reduce inertial power requirements for flight at elevated wing flapping frequencies. There is a continuing debate on the factors causing wing damage in insects including collisions with objects, mechanical stress during flight activity, and aging. This experimental study is engaged with the reasons and significance of wing damage for flight in the house fly Musca domestica. We determined natural wing area loss under two housing conditions and recorded flight activity and flight ability throughout the animals’ lifetime. Our data show that wing damage occurs on average after 6 h of flight, is sex-specific, and depends on housing conditions. Statistical tests show that both physiological age and flight activity have similar significance as predictors for wing damage. Tests on freely flying flies showed that minimum wing area for active flight is approximately 10-34% below the initial area and requires a left-right wing area asymmetry of less than approximately 25%. Our findings broadly confirm predictions from simple aerodynamic theory based on mean wing velocity and area, and are also consistent with previous wing damage measurements in other insect species.

PMID:34904650 | DOI:10.1242/jeb.242872