The study investigated whether there is a male reproductive system coronavirus disease‐2019 (COVID‐19) phenomenon. Thirty participants who met the inclusion criteria were enrolled in the study ...between April and May 2020. The participants were assigned in one of the three groups including COVID‐19 patients before and after treatment, and controls. Presence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) within the semen samples was investigated. Additionally, participant's demographics, semen parameters and serum sex hormone levels were compared between the groups. SARS‐CoV‐2 was not detected within the semen samples. Sperm morphology and serum sex hormone levels were significantly different between the groups. In the post hoc analysis, sperm morphology was significantly lower in the COVID‐19 patients. Patients before treatment had significantly lower serum FSH, LH and T levels than controls. However, patients after treatment had similar serum FSH, LH and T levels with controls and patients before treatment. In our opinion, COVID‐19 and its treatment had no specific deteriorative effect on male sexual health at a short‐time period. In the patients before treatment, decreased serum of T, FSH and LH levels was consistent with acute patient stress due to COVID‐19. Similarly, it seems that decreased sperm morphology was associated with the acute fever.
Expression levels of the major mammalian autophagy regulator Beclin 1 and its interaction with Bcl-2 regulate the switch between autophagic cell survival and apoptotic cell death pathways. However, ...some of the regulators and the precise mechanisms of these processes still remain elusive. Bag-1 (Bcl-2 associated athanogene-1), a member of BAG family proteins, is a multifunctional pro-survival molecule that possesses critical functions in vital cellular pathways. Herein, we report the role of Bag-1 on Bcl-2/Beclin 1 crosstalk through indirectly interacting with Beclin 1. Pull-down experiments suggested a molecular interaction between Bag-1 and Beclin 1 in breast cancer cell lines. On the other hand, in vitro binding assays showed that Bag-1/Beclin 1 interaction does not occur directly but occurs through a mediator molecule. Bag-1 interaction with p-Beclin 1 (T119), indicator of early autophagy, is increased during nutrient starvation suggesting involvement of Bag-1 in the autophagic regulation. Furthermore, CRISPR/Cas9-mediated Bag-1 knock-out in MCF-7 cells hampered cell survival and proliferation and resulted in decreased levels of total LC3 under starvation. Collectively, we suggest that Bag-1 modulates cell survival/death decision through maintaining macroautophagy as a component of Beclin 1-associated complexes.
Literature with regard to coronavirus disease 2019 (COVID-19) associated morbidities and the risk factors for death are still emerging. In this study, we investigated the presence of kidney damage ...markers and their predictive value for survival among hospitalized subjects with COVID-19.
Forty-seven participants was included and grouped as: 'COVID-19 patients before treatment', 'COVID-19 patients after treatment', 'COVID-19 patients under treatment in intensive care unit (ICU)', and 'controls'. Kidney function tests and several kidney injury biomarkers were compared between the groups. Cumulative rates of death from COVID-19 were determined using the Kaplan-Meier method. The associations between covariates including kidney injury markers and death from COVID-19 were examined, as well.
Serum creatinine and cystatin C levels, urine Kidney Injury Molecule-1 (KIM-1)/creatinine ratio, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI cystatin C, and CKD-EPI creatinine-cystatin C levels demonstrated significant difference among the groups. The most significant difference was noted between the groups 'COVID-19 patients before treatment' and 'COVID-19 patients under treatment in ICU'. Advancing age, proteinuria, elevated serum cystatin C, and urine KIM-1/creatinine ratio were all significant univariate correlates of death (p < 0.05, for all). However, only elevated urine KIM-1/creatinine ratio retained significance in an age, sex, and comorbidities adjusted multivariable Cox regression (OR 6.11; 95% CI: 1.22-30.53; p = 0.02), whereas serum cystatin C showing only a statistically non-significant trend (OR 1.42; 95% CI: 0.00-2.52; p = 0.09).
Our findings clearly demonstrated the acute kidney injury related to COVID-19. Moreover, urine KIM-1/creatinine ratio was associated with COVID-19 specific death.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
COVID‐19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+) and glutathione metabolism. Here it is ...investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID‐19 patients. CMAs include l‐serine, N‐acetyl‐l‐cysteine, nicotinamide riboside, and l‐carnitine tartrate, salt form of l‐carnitine. Placebo‐controlled, open‐label phase 2 study and double‐blinded phase 3 clinical trials are conducted to investigate the time of symptom‐free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID‐19 with CMAs lead to a more rapid symptom‐free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.
Open‐label phase‐2 and double‐blinded phase‐3 clinical trials show that administration of CMA accelerates the recovery of ambulatory COVID‐19 patients. By integrating clinical data with plasma metabolomics and inflammatory proteomics, it is shown that CMA improves immune response and regulates antioxidant, amino acid, and lipid metabolism. It is observed that administration of CMA is an effective and safe therapeutic strategy for COVID‐19 patients.
Turkey is one of the latest countries that COVID-19 disease was reported, with the first case on March 11, 2020, and since then, Istanbul became the epicenter of the pandemic in Turkey. Here, we ...reveal sequences of the virus isolated from three different patients with various clinical presentations.
Nasopharyngeal swab specimens of the patients were tested positive for the COVID-19 by qRT-PCR. Viral RNA extraction was performed from the same swab samples. Amplicon based libraries were prepared and sequenced using the Illumina NextSeq platform. Raw sequencing data were processed for variant calling and generating near-complete genome sequences. All three genomes were evaluated and compared with other worldwide isolates.
The patients showed various clinics (an asymptomatic patient, patient with mild disease, and with severe pulmonary infiltration). Amplicon-based next-generation sequencing approach successfully applied to generate near-complete genomes with an average depth of 2.616. All three viral genomes carried the D614G variant (G clade according to GISAID classification) with implications for the origin of a spread first through China to Europe then to Istanbul.
Here, we report the viral genomes circulating in Istanbul for the first time. Further sequencing of the virus isolates may enable us to understand variations in disease presentation and association with viral factors if there is any. In addition, the sequencing of more viral genomes will delineate the spread of disease and will guide and ease the necessary measures taken to stem the spread of the novel coronavirus.
Key Clinical Message
We used a multi‐gene panel testing to identify the germline variants in a mother‐daughter pair with early‐onset breast cancer, and detected one pathogenic protein‐truncating ...variant in BRCA2. Our results highlight the importance of genetic testing in identifying the pathogenic mutation running in cancer families.
We used a multi‐gene panel testing to identify the germline variants in a mother‐daughter pair with early onset breast cancer, and detected one pathogenic protein‐truncating variant in BRCA2. Our results highlight the importance of genetic testing in identifying the pathogenic mutation running in cancer families.
Key Clinical Message
We used a multi‐gene panel testing to identify the germline variants in a mother‐daughter pair with early‐onset breast cancer, and detected one pathogenic protein‐truncating ...variant in
BRCA
2
. Our results highlight the importance of genetic testing in identifying the pathogenic mutation running in cancer families.
Inherited pathogenic variants account for 5% to 10% of all breast cancer (BC) and colorectal cancer (CRC) cases. Here, we sought to profile the pathogenic variants in 25 cancer susceptibility genes ...in Turkish population. Germline pathogenic variants were screened in 732 BC patients, 189 CRC patients and 490 cancer‐free elderly controls, using next‐generation sequencing‐based multigene panel testing and multiplex ligation‐dependent probe amplification testing. Pathogenic variants were detected in 17.2% of high‐risk BC patients and 26.4% of high‐risk CRC patients. More than 95% of these variants were clinically actionable. BRCA1/2 and mismatch repair genes (MLH1, MSH2 and MSH6) accounted for two‐thirds of all pathogenic variants detected in high‐risk BC and CRC patients, respectively. Pathogenic variants in PALB2, CHEK2, ATM and TP53 were also prevalent in high‐risk BC patients (4.5%). BRCA1 exons 17‐18 deletion and CHEK2 c.592+3A>T were the most common variants predisposing to BC, and they are likely to be founder variants. Three frequent MUTYH pathogenic variants (c.884C>T, c.1437_1439delGGA and c.1187G>A) were responsible for all MUTYH biallelic cases (4.4% of high‐risk CRC patients). The total pathogenic variant frequency was very low in controls (2.4%) and in low‐risk BC (3.9%) and CRC (6.1%) patients. Our study depicts the pathogenic variant spectrum and prevalence in Turkish BC and CRC patients, guiding clinicians and health authorities for genetic testing applications and variant classification in Turkish population.
What's new?
Inherited cancer‐predisposing genetic variants vary in identity and frequency across populations, potentially impacting genetic testing for risk assessment and treatment. This study examined the spectrum and prevalence of pathogenic variants specifically among Turkish breast and colorectal cancer patients. A total of 25 cancer susceptibility genes were analyzed. Overall, pathogenic variants were mostly non‐recurrent or recurrent at low frequencies in the study population. The most notable exception, occurring at greater frequency, was deletion of exons 17‐18 in BRCA1, a potential founder variant that originated in northeastern Turkey. The findings could inform region‐specific strategies for genetic screening in cancer prevention.
•SARS-CoV-2 detection from saliva was more consistent during extended hospitalization and recovery.•Testing saliva samples before the end of isolation in individuals under treatment can be effective ...in spreading Covid-19.•Taking saliva samples along with the standard method before ending the isolation in individuals treated with hydroxychloroquine can be effective in minimizing contamination in the community by reducing the false negativity rate.
The gold standard method in the diagnosis of SARS-CoV-2 infection is the detection of viral RNA in the nasopharyngeal sample by RT-PCR. Recently, saliva samples have been suggested as an alternative sample. In the present study, we aimed to compare RT-PCR results in nasopharyngeal, oro-nasopharyngeal and saliva samples of COVID-19 patients. 98 of 200 patients were positive in RT-PCR analysis performed before the hospitalization. On day 0, at least one sample was positive in 67 % of 98 patients. The positivity rate was 83 % for both oro-nasopharyngeal and nasopharyngeal samples, while it was 63 % for saliva samples (p < 0.001). On day 5, RT-PCR was performed in 59 patients, 34 % had at least one positive result. The positivity rate was 55 % for both saliva and nasopharyngeal samples, while it was 60 % for oro-nasopharyngeal samples. Our study shows that the sampling saliva does not increase the sensitivity of RT-PCR tests at the early stages of infection. However, on the 5th day, viral RNA detection rates in saliva were similar to nasopharyngeal and oro-nasopharyngeal samples. In conclusion, we suggest that, in patients receiving treatment, RT-PCR in saliva, in addition to the standard samples, is important to determine the isolation period and control transmission.
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