Δευτέρα 26 Οκτωβρίου 2020

Safety of laser-generated shockwave treatment for bacterial biofilms in a cutaneous rodent model

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Abstract

Bacterial biofilms are often found in chronically infected wounds. Biofilms protect bacteria from antibiotics and impair wound healing. Surgical debridement is often needed to remove the biofilm from an infected wound. Laser-generated shockwave (LGS) treatment is a novel tissue-sparing treatment for biofilm disruption. Previous studies have demonstrated that LGS is effective in disrupting biofilms in vitro. In this study, we aim to determine the safety threshold of the LGS technology in an in vivo rodent model. To understand the in vivo effects of LGS on healthy cutaneous tissue, the de-haired dorsal skin of Sprague-Dawley rats were treated with LGS at three different peak pressures (118, 296, 227 MPa). These pressures were generated using a 1064 nm Nd/YAG laser (pulse duration 5 ns and laser fluence of 777.9 mJ) with laser spot size diameters of 2.2, 3.0, and 4.2 mm, respectively. Following treatment, the animals were observed for 72 h, and a small subset was eu thanized at 1-h, 24-h, and 72-h post-treatment and assessed for tissue injury or inflammation under histology. Each treatment group consisted of 9 rats (n = 3/time point for 1-h, 24-h, 72-h post-treatment). An additional 4 control (untreated) rats were included in the analysis, for a total of 31 animals. Gross injuries occurred in 21 (77%) animals and consisted of minor erythema, with prevalence positively correlated with peak pressure (p < 0.05). Of injuries under gross observation, 94% resolved within 24 h. Under histological analysis, the injuries and tissue inflammation were found to be localized to the epidermis and superficial dermis. LGS appears to be well tolerated by cutaneous tissue for the laser energy settings shown to be effective against bacterial biofilm in vitro. All injuries incurred, at even the highest peak pressures, were clinically mild and resolved within 1 day. This lends further support to the overall safety of LGS and serves to translate LGS towards in vivo efficacy studies.

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Red Marrow Absorbed Dose Calculation in Thyroid Cancer Patient Using a Simplified Excel Spreadsheet

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Red Marrow Absorbed Dose Calculation in Thyroid Cancer Patient Using a Simplified Excel Spreadsheet

Mol Imaging Radionucl Ther. 2020 10 19;29(3):124-131

Authors: Songprakhon R, Roysri K, Charoenphun P, Chuamsaamarkkee K

Abstract
Objectives: Absorbed dose to red marrow (Drm) can be calculated using blood dosimetry. However, this method is laborious and invasive. Therefore, image-based dosimetry is the method of choice. Nonetheless, the commercial software is expensive. The goal of this work was to develop a simplified excel spreadsheet for image-based radioiodine red marrow dosimetry.
Methods: The serial whole-body images (acquired at 2nd, 6th, 24th, 48th, and 72th hours) of 29 patients from the routine pretherapeutic dosimetry protocol were retrospectively reanalyzed. The commercial OLINDA/EXM image-based dosimetry software was used to calculate the whole-body time-integrated activity coefficient (TIACWB) and Drm [in terms of absorbed dose coefficient (drm)]. For the simplified excel spreadsheet, the wholebody count was obtained from the vendor-supplied software. Then, the TIACWB was computed by a fitting time-activity curve using an Excel function. S factor was taken from other publications and scaled according to the patient-specific mass. A comparison of the TIACWB and drm from both methods was done using a non-inferiority test using a paired t-test or the Wilcoxon signed-rank test.
Results: The TIACWB showed no significant difference between both methods (p=0.243). The calculated Drm from a simplified Excel spreadsheet was assumed to be statistically non-inferior to the commercial OLINDA/EXM image-based dosimetry software with the non-inferiority margin of 0.02 (p<0.05).
Conclusion: The dose assessment from a simplified Excel spreadsheet is feasible and relatively low cost compared to the commercial OLINDA/EXM image-based dosimetry software.

PMID: 33094576 [PubMed]

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Immortalization up-regulated protein promotes tumorigenesis and inhibits apoptosis of papillary thyroid cancer.

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Immortalization up-regulated protein promotes tumorigenesis and inhibits apoptosis of papillary thyroid cancer.

J Cell Mol Med. 2020 Oct 23;:

Authors: Lin L, Wen J, Lin B, Bhandari A, Zheng D, Kong L, Wang Y, Wang O, Chen Y

Abstract
The incidence of thyroid cancer is increasing in recent years worldwide, but the underlying mechanisms await further exploration. We utilized the bioinformatic analysis to discover that Immortalization up-regulated protein (IMUP) could be a potential oncogene in the papillary thyroid cancer (PTC). We verified this finding in several databases and locally validated cohorts. Clinicopathological features analyses showed that high expression of IMUP is positively related to malignant clinicopathological features in PTC. Braf-like PTC patients with higher IMUP expression had shorter disease-free survival. The biological function of IMUP in PTC cell lines (KTC-1 and TPC-1) was investigated using small interfering RNA. Our results showed that silencing IMUP suppresses proliferation, migration and invasion while inducing apoptosis in PTC cell lines. Changes of the expression of apoptosis-related molecules were identified by real-time quantitative polymerase chain reaction and Western blotting. We also found that YAP1 and TAZ, the critical effectors in the Hippo pathway, were down-regulated when the IMUP is silenced. Rescue experiments showed that overexpression of YAP1 reverses the tumour inhibitory effect caused by IMUP knockdown. Our study demonstrated that IMUP has an oncogenic function in PTC and might be a new target gene in the treatment of PTC.

PMID: 33094920 [PubMed - as supplied by publisher]

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FAM172A promotes follicular thyroid carcinogenesis and may be a marker of FTC.

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FAM172A promotes follicular thyroid carcinogenesis and may be a marker of FTC.

Endocr Relat Cancer. 2020 Nov;27(11):657-669

Authors: Xu PP, Zeng S, Xia XT, Ye ZH, Li MF, Chen MY, Xia T, Xu JJ, Jiao Q, Liu L, Li LX, Guo MG

Abstract
Our aims were to uncover the role of FAM172A (Family with sequence similarity 172 member A) in the pathogenesis of follicular thyroid carcinoma (FTC) and to evaluate its value in the differential diagnosis between malignant and benign thyroid follicular lesions. FAM172A expression was evaluated by q-PCR, immunoblotting and immunohistochemistry (IHC). The ability of proliferation, migration and invasion of cells were assessed by Cell Counting Kit-8 assay (CCK8), clone-formation and Transwell assays. Nude mouse tumorigenicity assays were used to investigate the role of FAM172A in the pathogenesis of FTC in vivo. The value of FAM172A in the differential diagnosis for FTC was assessed using 120 formalin-fixed paraffin-embedded (FFPE) tissues after the operation and 81 fine-needle aspiration biopsy (FNAB) samples before the operation. FAM172A was highly expressed in FTC tissues and FTC cell lines. Downregulation of FAM172A inhibited the proliferation, invasion and migration of FTC cells through Erk1/2 and JNK pathways. Subcutaneous tumorigenesis in nude mice showed that knockdown of FAM172A inhibited tumor growth and progression in vivo. The FAM172A IHC scores of 3.5 had 92% sensitivity and 63% specificity to separate FTC from benign/borderline thyroid follicular lesions, and 92% sensitivity and 80% specificity to discriminate FTC from benign thyroid follicular lesions in postoperative FFPE samples. The corresponding values were 75 and 78%, and 75 and 89% in preoperative FNA samples, respectively. FAM172A plays an important role in the pathogenesis of FTC through Erk1/2 and JNK pathways. FAM172A may be a potential marker for the preoperative diagnosis of FTC based on the IHC results of thyroid FNAB samples.

PMID: 33095186 [PubMed - as supplied by publisher]

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Nitrate contamination of drinking water, common in agricultural areas, increases the risk of certain cancers and impacts fetal development during pregnancy.

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Health and economic impact of nitrate pollution in drinking water: a Wisconsin case study.

Environ Monit Assess. 2020 Oct 23;192(11):724

Authors: Mathewson PD, Evans S, Byrnes T, Joos A, Naidenko OV

Abstract
Nitrate contamination of drinking water, common in agricultural areas, increases the risk of certain cancers and impacts fetal development during pregnancy. Building on previously published methodology, this study evaluates nitrate-attributable disease cases and adverse birth outcomes as well as their economic costs for Wisconsin, USA. Nitrate is the most common contaminant in groundwater in Wisconsin. Two-thirds of the state's residents use groundwater as the primary source of drinking water. Here, we analyze nitrate exposure from drinking water in Wisconsin based on nitrate test results for community water systems for the period of 2010-2017 and a novel methodology for estimating nitrate exposure for the 28% of state's residents who use private wells. We estimate that annually, 111-298 combined cases of colorectal, ovarian, thyroid, bladder, and kidney cancer in Wisconsin may be due to nitrate contamination of drinking water. Each year, up to 137-149 cases of very low birth weight, 72-79 cases of very preterm birth, and two cases of neural tube defects could be due to nitrate exposure from drinking water. The direct medical cost estimates for all nitrate-attributable adverse health outcomes range between $23 and $80 million annually. Simulating targeted reductions in the counties with the highest current drinking water nitrate concentrations resulted in similar reductions in adverse health outcomes as statewide reduction efforts, up to nitrate reductions of 20%. Time trend analysis suggests that groundwater nitrate concentrations are overall increasing. Thus, nitrate contamination of water supplies in Wisconsin is a public health problem that needs to be addressed.

PMID: 33095309 [PubMed - as supplied by publisher]

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Incidence of respiratory syncytial virus infection in children with congenital heart disease undergoing immunoprophylaxis with palivizumab in Pará state, north region of Brazil.

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Incidence of respiratory syncytial virus infection in children with congenital heart disease undergoing immunoprophylaxis with palivizumab in Pará state, north region of Brazil.

BMC Pediatr. 2019 08 28;19(1):299

Authors: de Souza RP, Ribeiro ALR, de Menezes SAF, Machado LFA

Abstract
BACKGROUND: Palivizumab prophylaxis for the human respiratory syncytial virus (HRSV) has been reported to reduce the risk of hospital admissions related to HRSV in children with congenital heart disease (CHD). These children are at high risk of developing severe lower respiratory tract infection (LRTI) due to HRSV infection. Our goal was to evaluate the incidence of HRSV infection in children with CHD after being submitted to immunoprophylaxis with palivizumab in Pará state, North region of Brazil.
METHODS: A prospective and observational cohort study was performed in children ≤2 years of age with CHD who received palivizumab immunoprophylaxis between January 1 and June 31, 2016. A questionnaire about basic non-medical care measures was applied to parents/legal representatives. Data on patients' demographic characteristics, household environment, and respiratory infections were evaluated. HRSV infection was determined by qPCR.
RESULTS: There were 104 children enrolled in this investigation and the results showed a mean age of 10.6 months, an average weight of 7.3 kg and 3.5 doses of palivizumab per children during seasonality of HRSV. Respiratory infection was observed in 27.9% of cases, of which 9.6% were LRTI. No case of children who received palivizumab immunoprophylaxis and developed influenza-like symptoms tested positive for HRSV.
CONCLUSION: Although the lack of a control group doesn't allow to affirm the effectiveness of HRSV passive immunization, the immunoprophylaxis with palivizumab appeared to be totally efficient in preventing respiratory infection by HRSV in children up to two years of age with CHD.

PMID: 31462289 [PubMed - indexed for MEDLINE]

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Influenza and respiratory syncytial virus infections in the oldest-old continent.

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Influenza and respiratory syncytial virus infections in the oldest-old continent.

Eur J Clin Microbiol Infect Dis. 2020 Nov;39(11):2085-2090

Authors: Boattini M, Almeida A, Christaki E, Cruz L, Antão D, Moreira MI, Bianco G, Iannaccone M, Tsiolakkis G, Khattab E, Kasapi D, Charrier L, Tosatto V, Marques TM, Cavallo R, Costa C

Abstract
SARS-CoV-2 dramatically revealed the sudden impact of respiratory viruses in our lives. Influenza and respiratory syncytial virus (RSV) infections are associated with high rates of morbidity, mortality, and an important burden on healthcare systems worldwide, especially in elderly patients. The aim of this study was to identify severity predictors in the oldest-old admitted with influenza and/or RSV infections. This is a multicenter, retrospective study of all oldest-old patients (≥ 85 years old) admitted for laboratory-confirmed influenza and/or RSV infection in three tertiary hospitals in Portugal, Italy, and Cyprus over two consecutive winter seasons. The outcomes included the following: pneumonia on infection presentation, use of non-invasive ventilation (NIV), and in-hospital death (IHD). The association with possible predictors, including clinical features and type of virus infection, was assessed using uni- and multivariable analyses. A total of 251 oldes t-old patients were included in the study. Pneumonia was evident in 32.3% (n = 81). NIV was implemented in 8.8% (n = 22), and IHD occurred in 13.9% (n = 35). Multivariable analyses revealed that chronic obstructive pulmonary disease (COPD) or asthma was associated with pneumonia (OR 1.86; 95% CI 1.02-3.43; p = 0.045). COPD or asthma (OR 4.4; 95% CI 1.67-11.6; p = 0.003), RSV (OR 3.12; 95% CI 1.09-8.92; p = 0.023), and influenza B infections (OR 3.77; 95% CI 1.06-13.5; p = 0.041) were associated with NIV use, respectively, while chronic kidney disease was associated with IHD (OR 2.50; 95% CI 1.14-5.51; p = 0.023). Among the oldest-old, chronic organ failure, such as COPD or asthma, and CKD predicted pneumonia and IHD, respectively, beyond the importance of viral virulence itself. These findings could impact on public health policies, such as fostering influenza immunization campaigns, home-based care programs, and end-of-life care. Filling knowledge ga ps is crucial to set priorities and advise on transition model of care that best fits the oldest-old.

PMID: 32594325 [PubMed - indexed for MEDLINE]

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