The COVID-19 pandemic is currently a severe challenge for healthcare workers, with a considerable impact on their mental health. In order to focus preventive and rehabilitation measures it's ...fundamental to identify risk factors of such psychological impairment. We designed an observational longitudinal study to systematically examine the psychological wellbeing of all employees in a large University Hospital in Italy, using validated psychometric scales in the context of the occupational physician's health surveillance, in collaboration with Psychiatric Unit.
The study started after ethical approval in August 2020. For each worker, the psychological wellbeing is screened in two steps. The first level questionnaire collects sociodemographic characteristics, personal and occupational COVID-19 exposure, worries and concerns about COVID-19, general psychological discomfort (GHQ-12), post-traumatic stress symptoms (IES-R) and anxiety (GAD-7). Workers who score above the cut-off in at least one scale are further investigated by the second level questionnaire composed by PHQ-9, DES-II and SCL-90. If second level shows psychological impairments, we offer individual specialist treatment (third level). We plan to follow-up all subjects to monitor symptoms and possible chronicization; we aim to investigate potential risk factors through univariate analysis and multivariate logistic regressions.
Preliminary results refer to a sample of 550 workers who completed the multi-step evaluation from August to December 2020, before vaccination campaign started. The participation rate was 90%. At first level screening, 39% of the subjects expressed general psychological discomfort (GHQ-12), 22% post-traumatic stress symptoms (IES-R), and 21% symptoms of anxiety (GAD-7). Women, nurses, younger workers, subjects with COVID-19 working exposure and with an infected family member showed significantly higher psychological impairment compared to colleagues. After the second level screening, 12% and 7% of all workers showed, respectively, depressive and dissociative symptoms; scorings were significantly associated with gender and occupational role. We are currently extending sample size and evaluating subjects over a period of further 12 months.
The possibility to perform a systematic follow-up of psychological wellbeing of all hospital workers, directly or indirectly exposed to pandemic consequences, constitutes a unique condition to detect individual, occupational, and non-occupational risk factors for psychological impairment in situations of prolonged stress, as well as variables associated with symptoms chronicization.
The duration of the QT interval is only a gross estimate of repolarization. Besides its limited accuracy and reproducibility, it does not provide information on the morphology of the T wave; thus, ...morphologic alterations such as notches can be only qualitatively described but not objectively quantified.
To measure the complexity of repolarization in the long-QT syndrome (LQTS) patients, we previously applied principal component analysis to body surface mapping and found it useful in distinguishing normal from abnormal repolarization patterns (sensitivity, 87%). In the present study, we applied principal component analysis to 12-lead Holter recordings. The index of complexity of repolarization that we have developed (CR24h) reflects the average 24-hour complexity of repolarization and is mathematically defined as the average ratio between the second and the first eigenvalue. We studied 36 LQTS patients and 40 control subjects. A mean of 22+/-1.3 ECG recordings at 1-hour intervals was used in each patient, and a total of 1655 recordings were analyzed. CR24h was significantly higher in LQTS than in control subjects (34+/-12% versus 13+/-3%; P<.0001). A CR24h exceeding 2 SD above the mean of the control group (>20%) was present in 32 of 36 patients (88%). The negative predictive value of CR24h in LQTS was 88%, and the combination of prolonged QT and abnormal CR24h identified all LQTS patients from normal subjects, including 4 affected symptomatic individuals with a normal QT interval duration, suggesting that CR24h provides information independent of QT duration.
Our data suggest that principal component analysis applied to 24-hour, 12-lead Holter recording adequately quantifies the complexity of ventricular repolarization and may become a useful noninvasive diagnostic tool in LQTS.
Several studies suggest that the holiday season, starting from the last week of November to the first or second week of January, could be critical to gaining weight. This study aims to review the ...literature to determine the effects of the holidays on body weight. In studies of adults, a significant weight gain was consistently observed during this period (0.4 to 0.9 kg, p<0.05). The only study in college students found an effect on body fat but not on weight (0.1 kg, p=0.71). The only study found in children did not show an effect on BMI percentile (−0.4%, p>0.05) during this period. Among individuals with obesity who attempt to lose weight, an increase in weight was observed (0.3 to 0.9 kg, significant in some but not in all studies), as well as increase in weight in motivated self-monitoring people (0.4 to 0.6%, p<0.001). Programs focused on self-monitoring during the holidays (phone calls and daily mailing) appeared to prevent weight gain, but information is limited. The holiday season seems to increase body weight in adults, even in participants seeking to lose weight and in motivated self-monitoring people, whereas in children, adolescents, and college students, very few studies were found to make accurate conclusions.
Ovarian cancer (OC) is considered the most lethal gynecological cancer, of which more than 65% cases are diagnosed in advanced stages, requiring platinum-based neoadjuvant chemotherapy (NACT).
A ...prospective-longitudinal study was conducted among women with advanced epithelial ovarian cancer (AEOC), III and IV stages, and treated with NACT, at the National Cancer Institute - Mexico, from July 2017 to July 2018. Serum samples were obtained for quantification of CA125 and HE4 using ELISA at the first and in each of the three NACT cycles. The therapeutic response was evaluated through standard tomography. We determined whether CA125 and HE4, alone or in combination, were associated with TR to NACT during follow up.
53 patients aged 38 to 79 years were included, 92.4% presented papillary serous subtype OC. Higher serum HE4 levels were observed in patients with non-tomographic response (6.89 vs 5.19 pmol/mL; p = 0.031), specially during the second (p = 0.039) and third cycle of NACT (p = 0.031). Multivariate-adjusted models showed an association between HE4 levels and TR, from the second treatment cycle (p = 0.042) to the third cycle (p = 0.033). Changes from baseline HE4 levels during the first cycle was negative associated with TR. No associations were found between CA125 and TR.
Serum HE4 levels were independently associated with TR among patients with AOEC treated with NACT, also a reduction between baseline HE4 and first chemotherapy levels was also independently associated with the TR. These findings might be relevant for predicting a lack of response to treatment.
The long-QT syndrome (LQTS) is a hereditary disorder characterized by an abnormally prolonged QT interval and by life-threatening arrhythmias. Recently, two of the genes responsible for LQTS have ...been identified: SCN5A, a voltage-dependent Na+ channel on chromosome 3 (LQT3), and HERG, responsible for the rapid component of the delayed rectifier current (IKr), on chromosome 7 (LQT2). We developed an in vitro model to attempt reproduction of the expected alterations in LQT3 and LQT2 patients. Guinea pig ventricular myocytes were exposed to anthopleura toxin A (anthopleurin), an inhibitor of the inactivation of the Na+ current, and to dofetilide, a selective blocker of IKr. Both interventions significantly prolonged action potential duration (APD), by 54 +/- 13 and 62 +/- 16 ms, respectively. Cells pretreated with anthopleurin significantly shortened APD in response to mexiletine, isoproterenol, and rapid pacing (from 264 +/- 38 to 226 +/- 32 ms after mexiletine, P < .001). On the contrary, cells exposed to dofetilide did not shorten the APD after mexiletine and even prolonged it after initial exposure to isoproterenol (from 280 +/- 25 to 313 +/- 20 ms, P < .001); during rapid pacing, APD was shortened but less (38 +/- 9 versus 60 +/- 11 ms, P < .05) than in anthopleurin-treated cells. This study shows that a cellular model for LQTS, based on the recent advances in molecular genetics, can provide adequate "phenotypes" of prolonged repolarization amenable to the testing of interventions of potential clinical relevance. We found differential responses to Na+ channel blockade, to beta-adrenergic stimulation, and to rapid pacing according to specific pretreatment with either anthopleurin (to mimic LQT3) or dofetilide (to mimic LQT2). These different responses in myocytes bear striking similarities with the differential response to analogous interventions in LQTS patients with mutations on the SCN5A and HERG genes.
This survey sampled today's European practices in the use of remote monitoring (RM) for the follow-up of active cardiovascular implantable electronic devices. Eighty-five per cent of the responding ...centres are currently using RM. For the majority, RM is expected to increase importantly within 5 years, and it has already led to a new organization of care based on dedicated allied professionals and/or the creation of RM units. There are still major limitations for the development of RM, such as ethical and legal aspects, reimbursement issues, and the lack of specific national- and European-updated guidelines which need to be informed.
Background: His Bundle (HB) pacing is a valid alternative to right ventricular pacing for patients with preserved His‐ventricle conduction who are candidates for permanent stimulation. Permanent ...pacing in the HB area enables Selective HB pacing (SHBP) or para‐Hisian pacing (PHP) to be achieved. The aim of our study was to draw up a set of easy criteria to differentiate and validate the two kinds of stimulations according to the pacing output and the ECG/EKG signals.
Methods and Results: From February to July 2005, 17 patients eligible for a pacemaker (PM) procedure underwent implantation with the Medtronic SelectSecure® lead (Medtronic, Minneapolis, MN, USA) screwed into the HB area.
SHBP was defined when the intrinsic QRS was equal, in both duration and morphology, to the paced QRS, the His‐Ventricular (H‐V) interval was equal to Pace‐Ventricular interval (Vp‐V) and, at low output, only the HB was captured, while increasing the output resulted in both the HB and right ventricular (RV) being captured (widening of QRS at high output). Conversely, PHP was defined when the intrinsic QRS differed from the paced one, either in morphology or in duration and, at high output, both the RV and HB were captured (non‐SHBP), while decreasing the output resulted in losing HB capture (widening of QRS at low output). According to these criteria, SHBP was achieved in 11 patients, while in the remaining 6, PHP was obtained. No adverse events were reported.
Conclusions: The above criteria enabled SHBP and PHP to be validated easily and clearly. A longer follow‐up will be needed in order to ascertain whether the clinical outcome of these two approaches differs.
The genes for the long QT syndrome (LQTS) linked to chromosomes 3 (LQT3) and 7 (LQT2) were identified as SCN5A, the cardiac Na+ channel gene, and as HERG, a K+ channel gene. These findings opened the ...possibility of attempting gene-specific control of ventricular repolarization. We tested the hypothesis that the QT interval would shorten more in LQT3 than in LQT2 patients in response to mexiletine and also in response to increases in heart rate.
Fifteen LQTS patients were studied. Six LQT3 and 7 LQT2 patients were treated with mexiletine, and its effects on QT and QTc were measured. Mexiletine significantly shortened the QT interval among LQT3 patients (QTc from 535 +/- 32 to 445 +/- 31 ms, P < .005) but not among LQT2 patients (QTc from 530 +/- 79 to 503 +/- 60 ms, P = NS). LQT3 patients (n = 7) shortened their QT interval in response to increases in heart rate much more than LQT2 patients (n = 4) and also more than 18 healthy control subjects (9.45 +/- 3.3 versus 3.95 +/- 1.97 and 2.83 +/- 1.33, P < .05; data expressed as percent reduction in QT per 100-ms shortening in RR). Among these patients, there is also a trend for LQT2 patients to have syncope or cardiac arrest under emotional or physical stress and for LQT3 patients to have cardiac events either at rest or during sleep.
This is the first study to demonstrate differential responses of LQTS patients to interventions targeted to their specific genetic defect. These findings also suggest that LQT3 patients may be more likely to benefit from Na+ channel blockers and from cardiac pacing because they would be at higher risk of arrhythmia at slow heart rates. Conversely, LQT2 patients may be at higher risk to develop syncope under stressful conditions because of the combined arrhythmogenic effect of catecholamines with the insufficient adaptation of their QT interval when heart rate increases.
Two robust mutlivariable controllers, H∞ and a decentralized quantitative feedback theory (QFT), are designed in the frequency domain for the 2 × 2 looper system in a steel hot rolling mill to keep ...stability in the presence of parametric uncertainties. The H∞ controller is designed by using the mixed sensitivity approach, while the multivariable decentralized QFT is designed by the extension of the sequential loop closing method presented elsewhere. Stability robustness conditions are verified in the frequency domain, while simulations in time domain are carried out to evaluate the controllers and compare their performance along with that of proportional + integral (PI) and single input single output (SISO) QFT controllers designed earlier. The QFT controller shows the best balance among the performance indicators analyzed here; however, at the expenses of using higher power in one of the control inputs.
Heterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican ...population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients.
We searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control.
We identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53.
Among Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.
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