Simple concentration method enables the use of gargle and mouthwash instead of nasopharyngeal swab sampling for the diagnosis of COVID-19 by PCR

European Journal of Clinical Microbiology & Infectious Diseases - Since its emergence in December 2019, SARS-CoV-2 is causing one of the most devastating pandemics in human history. Currently,...     

Sarcopenia is associated with increased severe postoperative complications after colon cancer surgery

IntroductionStudies have shown that sarcopenia is associated with poor outcomes in patients with gastrointestinal cancer undergoing surgery. We aimed to investigate the relationship between postoperative complications of sarcopenic patients who had been operated on for colon cancer and the effects on short-term mortality.Material and methodsIn this study, patients who had undergone colon cancer surgery between January 2013 and December 2018 were collected retrospectively. Sarcopenia was diagnosed by the skeletal muscle index (SMI) derived from a preoperative computed tomography scan. Multiple logistic regression analysis was performed to determine whether sarcopenia is associated with postoperative major complications (POMC).ResultsThe study included 160 patients with a mean age of 62.4 ±12.6 years. Clavien-Dindo grade 1–2 (minor) complications were not significantly different between the groups (p = 0.896). However, grade ≥ 3 (major) complications were detected in 13 (17.8%) patients in the sarcopenic group (SG) and in 5 patients in the non-sarcopenic group (NSG) (5.7%) (p = 0.016). Length of intensive care unit (ICU) stay was longer in SG (p = 0.002) and there was no difference between 1-month and 6-month mortality rates (p = 0.273 and p = 0.402, respectively). According to univariate analyses, sarcopenia and age over 65 years were related to POMC. In multivariate analyses, sarcopenia (odds ratio = 3.039; 95% confidence interval 1.008–9.174; p = 0.048) and advanced age (odds ratio = 3.246; 95% confidence interval 1.078–9.803; p = 0.036) were found to be independent risk factors for POMC.ConclusionsThis study showed that while sarcopenia is a risk factor for POMC, sarcopenia also prolongs the duration of ICU stay. Also sarcopenia has no effect on short-term mortality.     

Heterozygous germline BLM mutations increase susceptibility to asbestos and mesothelioma

Rare biallelic BLM gene mutations cause Bloom syndrome. Whether BLM heterozygous germline mutations (BLM^+/−) cause human cancer remains unclear. We sequenced the germline DNA of 155 mesothelioma patients (33 familial and 122 sporadic). We found 2 deleterious germline BLM^+/− mutations within 2 of 33 families with multiple cases of mesothelioma, one from Turkey (c.569_570del; p.R191Kfs*4) and one from the United States (c.968A>G; p.K323R). Some of the relatives who inherited these mutations developed mesothelioma, while none with nonmutated BLM were affected. Furthermore, among 122 patients with sporadic mesothelioma treated at the US National Cancer Institute, 5 carried pathogenic germline BLM^+/− mutations. Therefore, 7 of 155 apparently unrelated mesothelioma patients carried BLM^+/− mutations, significantly higher (P = 6.7E-10) than the expected frequency in a general, unrelated population from the gnomAD database, and 2 of 7 carried the same missense pathogenic mutation c.968A>G (P = 0.0017 given a 0.00039 allele frequency). Experiments in primary mesothelial cells from Blm^+/− mice and in primary human mesothelial cells in which we silenced BLM revealed that reduced BLM levels promote genomic instability while protecting from cell death and promoted TNF-α release. Blm^+/− mice injected intraperitoneally with asbestos had higher levels of proinflammatory M1 macrophages and of TNF-α, IL-1β, IL-3, IL-10, and IL-12 in the peritoneal lavage, findings linked to asbestos carcinogenesis. Blm^+/− mice exposed to asbestos had a significantly shorter survival and higher incidence of mesothelioma compared to controls. We propose that germline BLM^+/− mutations increase the susceptibility to asbestos carcinogenesis, enhancing the risk of developing mesothelioma.

In the United States, the incidence rate of mesothelioma varies between fewer than one case per 100,000 persons in states with no asbestos industry to two to three cases per 100,000 persons in states with an asbestos industry (1, 2). Asbestos causes DNA damage and apoptosis (3) and promotes a chronic inflammatory reaction that supports the emergence of malignant cells (4). Fortunately, only a small fraction of exposed individuals develop mesothelioma; for example, 4.6% of deaths in miners who worked in asbestos mines for over 10 y were caused by mesothelioma (1). Therefore, multiple cases of mesothelioma in the same family are rare and suggest genetic predisposition (5). In 2001, we discovered that susceptibility to mesothelioma was transmitted in a Mendelian fashion across multiple generations in some Turkish families exposed to the carcinogenic fiber erionite, pointing to gene × environment interaction (G×E) as the cause (6). In 2011, we discovered that carriers of heterozygous germline BRCA1-associated protein–1 (BAP1) mutations (BAP1^+/−) developed mesothelioma and uveal melanoma (5), findings expanded and confirmed by us and by multiple research teams (reviewed in refs. 1, 7, 8). Moreover, heterozygous germline Bap1 mutations (Bap1^+/−) significantly increased susceptibility to asbestos-induced mesothelioma in mice (9, 10), evidence of G×E. Reduced BAP1 levels impair DNA repair (11) as well as different forms of cell death (3, 12) and induce metabolic alterations (13–15) that together favor cancer development and growth.Recent studies revealed that mesothelioma may also develop among carriers of germline mutations of additional tumor-suppressor genes that cause well-defined cancer syndromes, including MLH1 and MLH3 (Lynch syndrome), TP53 (Li–Fraumeni syndrome), and BRCA1-2 (Breast and Ovarian Cancer syndrome) (16, 17). When all germline mutations are combined, it has been estimated that about 12% of mesotheliomas occur in carriers of heterozygous germline mutations of BAP1, the most frequent mutation among patients with mesothelioma, or of other tumor suppressors. Some of these mutations may sensitize the host to asbestos carcinogenesis, according to a G×E scenario (17). Thus, presently, mesothelioma is considered an ideal model to study G×E in cancer (17). As part of the Healthy Nevada Project (HNP), we are studying G×E in northern Nevada, a region with an unusually high risk of exposure to carcinogenic minerals and arsenic, which may be related to the high cancer rates in this region (18). We are investigating genetic variants that may increase cancer risk upon exposure to carcinogens to implement preventive strategies.Biallelic mutations of the Bloom syndrome gene (BLM) cause Bloom syndrome, an autosomal-recessive tumor predisposition syndrome characterized by pre- and postnatal growth deficiency, photosensitivity, type 2 diabetes, and greatly increased risk of developing various types of cancers. BLM is a RecQ helicase enzyme that modulates DNA replication and repair of DNA damage by homologous recombination (19). In patients affected by Bloom syndrome, the absence of the BLM protein causes chromosomal instability, increased number of sister chromatid exchanges, and increased numbers of micronuclei (20–22). In addition, BLM is required for p53-mediated apoptosis (23), a process critical to eliminate cells that have accumulated DNA damage. Impaired DNA repair together with altered apoptosis resulted in increased cancer incidence (17, 24). Of course, inactivating germline BLM heterozygous (BLM^+/−) mutations are much more common than biallelic BLM (BLM^−/−) mutations, with an estimated frequency in the general population of 1 in 900 based on data from the Exome Aggregation Consortium (25). BLM^+/− mutation carriers do not show an obvious phenotype; however, some studies have suggested that carriers of these mutations may have an increased cancer risk (17, 24). Mice carrying Blm^+/− mutations are prone to develop a higher rate of malignancies in the presence of contributing factors, such as concurrent heterozygous mutations of the adenomatous polyposis coli (Apc) gene, or upon infection with murine leukemia virus (26). However, in studies in which Blm^+/− mice were crossed with tuberous sclerosis 1-deficient (Tsc1^+/−) mice that are predisposed to renal cystadenomas and carcinomas, Wilson et al. found that Tsc1^+/− Blm^+/− mice did not show significantly more renal cell carcinomas compared with Tsc1^+/− Blm^WT mice (27). In humans, a large study involving 1,244 patients with colon cancer and 1,839 controls of Ashkenazi Jewish ancestry, in which BLM^+/− frequency is as high as 1 in 100 individuals (28), suggested that carriers of germline BLM^+/− mutations might have a twofold increase in colorectal cancer (CRC) (29). A smaller study did not confirm these results, but reported a trend of increasing incidence of adenomas—premalignant lesions—among BLM^+/− mutation carriers (30). In addition, BLM^+/− mutations were found overrepresented among early-onset (<45 y old) CRC patients (25). Other studies associated BLM^+/− mutations to an increased risk of breast (31, 32) and prostate cancer (33), but the low power of these studies hampered definite conclusions. In summary, it appears possible that BLM^+/− mutations may increase cancer risk in the presence of contributing factors.     

Evaluation of the bond strength between aged composite cores and luting agent

PURPOSE

The aim of this study was to evaluate effect of different surface treatment methods on the bond strength between aged composite-resin core and luting agent.

MATERIALS AND METHODS

Seventy-five resin composites and also seventy-five zirconia ceramic discs were prepared. 60 composite samples were exposed to thermal aging (10,000 cycles, 5 to 55℃) and different surface treatment. All specimens were separated into 5 groups (n=15): 1) Intact specimens 2) Thermal aging-air polishing 3) Thermal aging- Er:YAG laser irradiation 4) Thermal aging- acid etching 5) Thermal-aging. All specimens were bonded to the zirconia discs with resin cement and fixed to universal testing machine and bond strength testing loaded to failure with a crosshead speed of 0.5 mm/min. The fractured surface was classified as adhesive failure, cohesive failure and adhesive-cohesive failure. The bond strength data was statistically compared by the Kruskal-Wallis method complemented by the Bonferroni correction Mann-Whitney U test. The probability level for statistical significance was set at α=.05.

RESULTS

Thermal aging and different surface treatment methods have significant effect on the bond strength between composite-resin cores and luting-agent (P<.05). The mean baseline bond strength values ranged between 7.07 ± 2.11 and 26.05 ± 6.53 N. The highest bond strength of 26.05 ± 6.53 N was obtained with Group 3. Group 5 showed the lowest value of bond strength.

CONCLUSION

Appropriate surface treatment method should be applied to aged composite resin cores or aged-composites restorations should be replaced for the optimal bond strength and the clinical success.     

Urothelial cancer of bladder in young versus older adults: Clinical and pathological characteristics and outcomes

Bladder urothelial carcinoma is rare in young adults and occurs more commonly in older individuals. The aim of this study was to compare the clinical behavior, pathologic characteristics, and prognosis of urothelial carcinoma of urinary bladder in young versus older adults. A retrospective review of our records between 2007 and 2013 identified 56 patients (42 males and 14 females) with transitional cell carcinoma of the bladder who were less than 40 years old. Clinical and pathological parameters of patients who were less than 40 years of age were compared with those of a series of patients older than 40 years of age (the control group) during the same period. A survival analysis was performed using the Kaplan–Meier method and log-rank test, and Cox regression was performed to identify clinical parameters that affected the clinical outcomes. The mean age was 29.21 years (range, 5–40 years) for patients less than 40 years old and 61.66 years (range, 41–75) for those older than 40 years. The mean follow-up was 40.26 months (range, 12–65 months) for young patients and 42.57 months (range, 12–72 months) for the older patients. Young bladder cancer patients had smaller-sized tumors (less than 3 cm), less high-grade cancers, higher papillary urothelial neoplasms of low malignant potential, and low-grade tumors than patients older than 40 years. Multivariate logistic regression analysis predicted tumor recurrence in young patients with high-grade tumors [odds ratio (OR), 1.959; 95% confidence interval (CI), 1.235–2.965; p = 0.046] and tumors larger than 3 cm (OR, 1.772; 95% CI, 1.416–1.942; p = 0.032). The 5-year overall survival rate was 100% for young patients and 88.1% for older patients. No difference was observed in the recurrence-free (p = 0.321) and progression-free (p = 0.422) survival rates between the two groups. We concluded that although the clinical stage distribution, natural history, and outcomes of bladder urothelial cancer in young adults are similar to those in their older counterparts, clinicians must be aware that patients under 40 years of age presented with higher-grade and larger (>3 cm) tumors and are more likely to experience tumor recurrence.     

Effects of polyols on the quality characteristics of sucrose-free milk chocolate produced in a ball mill

Sucrose-free milk chocolates containing different types of bulk (isomalt, xylitol and maltitol) and high intensity (Stevia) sweeteners were produced by using a ball mill. The main quality characteristics of the formulated chocolates were evaluated and compared with those of the conventional sample containing sucrose. The Casson model was the best fitting model for the rheological data. Casson viscosity and Casson yield stress were significantly affected by the type of bulking agent in chocolates formulated with xylitol (p < 0.05). However xylitol notably improved the overall acceptability according to the sensory analysis results. Chocolates containing the sucrose replacers demonstrated lower T_onset values and higher enthalpy than the control sample. Sucrose-free chocolates illustrated a higher degree of particle agglomeration. Bulk sweeteners meanwhile seem to have high potential for milk chocolate production with low calorie values by using the ball mill technique. Industrial applications: the production of sucrose-free chocolates with conventional methods requires a lot of time and energy. Recently, using alternative methods for chocolate production has been raising interest in many small industries. This study proposed a ball mill method for the preparation of sucrose-free milk chocolates with physiochemical properties almost ranging in the standard limit defined for chocolate. Although using the ball mill method presents a more cost-effective technique for chocolate production and provides shorter processing times for small chocolate industries, it seems to be less efficient in evaporating moisture than the conventional processing. Challenges are still ahead for upgrading this alternative technique to be efficient in evaporating more moisture during operation ending in a high quality product.

Sucrose-free milk chocolates containing different types of bulk (isomalt, xylitol and maltitol) and high intensity (Stevia) sweeteners were produced by using a ball mill.