Depression and anxiety in healthcare professionals during the COVID-19 pandemic.

Healthcare staff have been at the centre of the fight against the COVID-19 pandemic, facing diverse work-related stressors. Building upon studies from various countries, we aimed to investigate (1) the prevalence of various work-related stressors among healthcare professionals in Germany specific to the COVID-19 pandemic, (2) the psychological effects of these stressors in terms of clinical symptoms, and (3) the healthcare professionals' help-seeking behaviour. To this end, N = 300 healthcare professionals completed an online survey including the ICD-10 Symptom Rating checklist (ISR), event-sampling questions on pandemic-related stressors and self-formulated questions on help-seeking behaviour. Participants were recruited between 22 May and 22 July 2020. Findings were analysed using t tests, regressions and comparisons to large clinical and non-clinical samples assessed before and during the pandemic. Results show that healthcare professionals were most affected by protective measures at their workplace and changes in work procedures. Psychological symptoms, particularly anxiety and depression, were significantly more severe than in a non-clinical pre-pandemic sample and in the general population during the pandemic. At the same time, most professionals indicated that they would not seek help for psychological concerns. These findings indicate that healthcare employers need to pay greater attention to the mental health of their staff.

The Long-Term Effect of a Quality Improvement Intervention in the Management of Bronchiolitis.

Quality improvement interventions have been shown to improve adherence with bronchiolitis treatment guidelines; however, the long-term effect of these interventions is unclear. We show that while such an intervention led to a long-lasting change, this was attenuated with time. Repeated interventions are required to maintain guideline adherence.

Patient outcomes following implantation with a trifocal toric IOL: twelve-month prospective multicentre study.

PURPOSE: To evaluate clinical outcomes with a premium diffractive-refractive trifocal toric intraocular lens (IOL) over a 12-month period. METHODS: Multicentre prospective clinical trial including 227 eyes of 114 patients undergoing cataract surgery with bilateral implantation of the AT LISA tri toric 939MP IOL (Carl Zeiss Meditec, Jena, Germany). One patient was implanted unilaterally. Outcome measures were: visual acuity, manifest refraction, reading performance, contrast sensitivity, defocus curve, patient satisfaction and subjective quality of vision. Alpins vector analysis was used to evaluate astigmatic changes. RESULTS: 12-month follow up results of binocular uncorrected distance, intermediate and near visual acuity were ≤0.3 logMAR in 99.0%, 98.10% and 91.40% of eyes, respectively. 79.7% of eyes had a cylinder value of ±0.50 D at 12 months post-surgery. Contrast sensitivity was in the normal range at 6 months post-surgery. The defocus curve exhibited a smooth transition between far and near foci. Vector analysis showed a mean magnitude of error of -0.16 ± 0.48 D. Mean binocular distance-corrected reading visual acuity was 0.15 ± 0.13 logRAD at 6 months postoperatively. 93.3%, 89.4% and 84.6% of patients expressed satisfaction (good or very good) with distance, intermediate and near vision, respectively, 12 months after surgery. Most (≥95%) patients felt that visual disturbances, including halos, glare, focusing difficulties and depth perception, caused little or no disturbance. CONCLUSIONS: The diffractive-refractive trifocal toric IOL, AT LISA tri toric 939MP, provides effective distance, intermediate and near visual acuity in eyes with corneal astigmatism. Patient satisfaction was high and 98.1% of patients expressed satisfaction with the IOL implanted.

Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study.

BACKGROUND: Glyphosate (GLY) is the most heavily used herbicide worldwide but the extent of exposure in human pregnancy remains unknown. Its residues are found in the environment, major crops, and food items that humans, including pregnant women, consume daily. Since GLY exposure in pregnancy may also increase fetal exposure risk, we designed a birth-cohort study to determine exposure frequency, potential exposure pathways, and associations with fetal growth indicators and pregnancy length. METHOD: Urine and residential drinking water samples were obtained from 71 women with singleton pregnancies living in Central Indiana while they received routine prenatal care. GLY measurements were performed using liquid chromatography-tandem mass spectrometry. Demographic and survey information relating to food and water consumption, stress, and residence were obtained by questionnaire. Maternal risk factors and neonatal outcomes were abstracted from medical records. Correlation analyses were used to assess relationships of urine GLY levels with fetal growth indicators and gestational length. RESULTS: The mean age of participants was 29 years, and the majority were Caucasian. Ninety three percent of the pregnant women had GLY levels above the limit of detection (0.1 ng/mL). Mean urinary GLY was 3.40 ng/mL (range 0.5-7.20 ng/mL). Higher GLY levels were found in women who lived in rural areas (p = 0.02), and in those who consumed > 24 oz. of caffeinated beverages per day (p = 0.004). None of the drinking water samples had detectable GLY levels. We observed no correlations with fetal growth indicators such as birth weight percentile and head circumference. However, higher GLY urine levels were significantly correlated with shortened gestational lengths (r = - 0.28, p = 0.02). CONCLUSIONS: This is the first study of GLY exposure in US pregnant women using urine specimens as a direct measure of exposure. We found that > 90% of pregnant women had detectable GLY levels and that these levels correlated significantly with shortened pregnancy lengths. Although our study cohort was small and regional and had limited racial/ethnic diversity, it provides direct evidence of maternal GLY exposure and a significant correlation with shortened pregnancy. Further investigations in a more geographically and racially diverse cohort would be necessary before these findings could be generalized.

An advanced lithium-air battery exploiting an ionic liquid-based electrolyte.

A novel lithium-oxygen battery exploiting PYR14TFSI-LiTFSI as ionic liquid-based electrolyte medium is reported. The Li/PYR14TFSI-LiTFSI/O2 battery was fully characterized by electrochemical impedance spectroscopy, capacity-limited cycling, field emission scanning electron microscopy, high-resolution transmission electron microscopy, and X-ray photoelectron spectroscopy. The results of this extensive study demonstrate that this new Li/O2 cell is characterized by a stable electrode-electrolyte interface and a highly reversible charge-discharge cycling behavior. Most remarkably, the charge process (oxygen oxidation reaction) is characterized by a very low overvoltage, enhancing the energy efficiency to 82%, thus, addressing one of the most critical issues preventing the practical application of lithium-oxygen batteries.

Macrolides for the long-term management of asthma--a meta-analysis of randomized clinical trials.

BACKGROUND: Macrolide antibiotics, which have anti-inflammatory and immune modulatory effects, have been studied as adjuncts for the management of asthma. However, results have been contradictory and trials underpowered. We therefore sought to conduct a meta-analysis of randomized controlled trials (RCT). METHODS: All RCT of prolonged macrolides (3+ weeks) for asthma treatment, published up to January 2013 in MEDLINE, Scopus, CINAHL, Highwire, and The Cochrane Collaboration Library, were included. Fixed- or random-effects models were used to calculate pooled weighted or standard mean differences (WMD or SMD, respectively). RESULTS: A total of 12 studies were included for analysis. The pooled effect of macrolides on FEV1 (eight trials, 381 subjects) was not significant (SMD 0.05, 95% CI -0.14-0.25), but there was a significant increase in peak expiratory flow (four trials, 419 subjects; WMD 6.7, 95% CI 1.35-12.06). Pooled analysis also showed significant improvements in symptom scores (eight studies, 478 subjects; WMD -0.46, 95% CI -0.60 to -0.32), quality of life (five trials, 346 subjects; WMD 0.18, 95% CI 0.001-0.37), and airway hyper-reactivity (two trials, 131 subjects; SMD 1.99, 95% CI 0.46-3.52). Post hoc evaluation showed limited statistical power to detect significant differences in FEV1. CONCLUSIONS: Macrolide administration for asthma for three or more weeks was not associated with improvement in FEV1, but produced significant improvements in peak expiratory flow, symptoms, quality of life, and airway hyper-reactivity. Macrolides may therefore be beneficial as adjunct asthma therapy. Future trials, focusing on long-term safety and effectiveness, should use standardized outcomes and procedures.

Type 1 diabetes and prolonged fasting.

AIMS: Fasting is common in several religions. The aims of this study were to determine if prolonged fasting (> 25 h) is safe for individuals with Type 1 diabetes and to identify factors associated with success. METHODS: Patients intending to fast were instructed on insulin dose adjustments, frequent glucose monitoring and when to terminate the fast using a standard protocol. Clinical and epidemiological factors were recorded and a comparison was made between successful and unsuccessful fasters. RESULTS: Of 56 subjects who intended to fast, 37 (65%) were successful. Individuals terminated their fast in the presence of either hypoglycaemia or hyperglycaemia and adherence to the protocol was high. There were no serious side-effects of fasting. Successful fasters had greater reductions in insulin dosage and higher HbA(1c). There were no differences between individuals taking intermittent insulin injections and those with continuous infusion pumps. CONCLUSIONS: Persons with Type 1 diabetes can participate safely in prolonged fasts provided they reduce their usual insulin dose significantly and adhere to guidelines regarding glucose monitoring and indications for terminating fasting.

Type 1 diabetes risk assessment: improvement by follow-up measurements in young islet autoantibody-positive relatives.

AIMS/HYPOTHESIS: Combinations of autoantibody characteristics, including antibody number, titre, subclass and epitope have been shown to stratify type 1 diabetes risk in islet autoantibody-positive relatives. The aim of this study was to determine whether autoantibody characteristics change over time, the nature of such changes, and their implications for the development of diabetes. METHODS: Five-hundred and thirteen follow-up samples from 141 islet autoantibody-positive first-degree relatives were tested for islet autoantibody titre, IgG subclass, and GAD and IA-2 antibody epitope. All samples were categorised according to four risk stratification models. Relatives had a median follow-up of 6.8 years and 48 developed diabetes during follow-up. Survival analysis was used to determine the probability of change in risk category and of progression to diabetes. RESULTS: For each stratification model, the majority of relatives (71-81%) remained in the same risk category throughout follow-up. In the remainder, changes occurred both from lower to higher and from higher to lower risk categories. For all four models, relatives aged < 15 years were more likely to change risk category than those aged >15 years (0.001 < p < 0.03). Relatives whose autoantibody status changed from low- to high-risk categories had a higher risk of diabetes than relatives who remained in low-risk categories, and inclusion of autoantibody status during follow-up improved diabetes risk stratification in Cox proportional hazards models (p < 0.001). CONCLUSIONS/INTERPRETATION: Changes in islet autoantibodies are relevant to pathogenesis, and are likely to signal alterations in the disease process. Detection of changes through follow-up measurement will improve diabetes risk stratification, particularly in young individuals.

EGF/ErbB receptor family in ovarian cancer.

In summary, the EGF/ErbB family of receptor tyrosine kinases has been shown to play a key role in normal ovarian follicle development, and cell growth regulation of the ovarian surface epithelium. Disregulation of these normal growth regulatory pathways, including overexpression and/or mutation of EGFR/ErbB receptor family members, as well as elements of their downstream signalling pathways, have been shown to contribute to the etiology and progression of epithelial ovarian cancer. It is, therefore, not surprising that these gene products, and their related soluble receptor isoforms may have clinical utility as tumor and/or serum biomarkers of disease activity. Moreover, since several of these soluble receptor isoforms have potent growth inhibitory activity, and are naturally occurring in the circulation, they are ideal candidates for the development of novel therapeutics for the treatment of ovarian cancer patients.

Bmp2b and Oep promote early myocardial differentiation through their regulation of gata5.

Members of both the bone morphogenetic protein (Bmp) and EGF-CFC families have been implicated in vertebrate myocardial development. Zebrafish swirl (swr) encodes Bmp2b, a member of the Bmp family required for patterning the dorsoventral axis. Zebrafish one-eyed pinhead (oep) encodes a maternally and zygotically expressed member of the EGF-CFC family essential for Nodal signaling. Both swr/bmp2b and oep mutants exhibit severe defects in myocardial development. swr/bmp2b mutants exhibit reduced or absent expression of nkx2.5, an early marker of the myocardial precursors. Embryos lacking zygotic oep (Zoep mutants) display cardia bifida and, as we show here, also display reduced or absent nkx2.5 expression. Recently, we have demonstrated that the zinc finger transcription factor Gata5 is an essential regulator of nkx2.5 expression. In this paper, we investigate the relationships between bmp2b, oep, gata5, and nkx2.5. We show that both swr/bmp2b and Zoep mutants exhibit defects in gata5 expression in the myocardial precursors. Forced expression of gata5 in swr/bmp2b and Zoep mutants restores robust nkx2.5 expression. Moreover, overexpression of gata5 in Zoep mutants restores expression of cmlc1, a myocardial sarcomeric gene. These results indicate that both Bmp2b and Oep regulate gata5 expression in the myocardial precursors, and that Gata5 does not require Bmp2b or Oep to promote early myocardial differentiation. We conclude that Bmp2b and Oep function at least partly through Gata5 to regulate nkx2.5 expression and promote myocardial differentiation. We integrate these and other data to propose a pathway of the molecular events regulating early myocardial differentiation in zebrafish.

Comparative genomic sequence analysis and isolation of human and mouse alternative EGFR transcripts encoding truncated receptor isoforms.

This study presents the annotated genomic sequence and exon-intron organization of the human and mouse epidermal growth factor receptor (EGFR) genes located on chromosomes 7p11.2 and 11, respectively. We report that the EGFR gene spans nearly 200 kb and that the full-length 170-kDa EGFR is encoded by 28 exons. In addition, we have identified two human and two mouse alternative EGFR transcripts of 2.4-3.0 kb using both computational and experimental methods. The human 3.0-kb and mouse 2.8-kb EGFR mRNAs are predominantly expressed in placenta and liver, respectively, and both transcripts encode 110-kDa truncated receptor isoforms containing only the extracellular ligand-binding domain. We also have demonstrated that the aberrant 2.8-kb EGFR transcript produced by the human A431 carcinoma cell line is generated by splicing to a recombinant 3'-terminal exon located in EGFR intron 16, which apparently was formed as a result of a chromosomal translocation. Finally, we have shown that the human, mouse, rat, and chicken 1.8- to 3.0-kb alternative EGFR transcripts are generated by distinct splicing mechanisms and that each of these mRNAs contains unique 3' sequences that are not evolutionarily conserved. The presence of truncated receptor isoforms in diverse species suggests that these proteins may have important functional roles in regulating EGFR activity.

Multiple roles for Gata5 in zebrafish endoderm formation.

Previous studies have indicated that gata5, a zinc-finger transcription factor gene, is required for the development of the zebrafish gut tube. Here, we show that gata5 mutants also display defects in the development of other endodermal organs such as the liver, pancreas, thyroid and thymus. gata5 is expressed in the endodermal progenitors from late blastula stages, suggesting that it functions early during endoderm development. We indeed find that during gastrulation stages, gata5 mutants form fewer endodermal cells than their wild-type siblings. In addition, the endodermal cells that form in gata5 mutants appear to express lower than wild-type levels of endodermal genes such as sox17 and axial/foxA2. Conversely, overexpression of gata5 leads to expanded endodermal gene expression. These data indicate that Gata5 is involved both in the generation of endodermal cells at late blastula stages and in the maintenance of endodermal sox17 expression during gastrulation. We have also analyzed the relationship of Gata5 to other factors involved in endoderm formation. Using complementary mutant and overexpression analyses, we show that Gata5 regulates endoderm formation in cooperation with the Mix-type transcription factor Bon, that Gata5 and Bon function downstream of Nodal signaling, and that cas function is usually required for the activity of Gata5 in endoderm formation. Finally, we show that fau/gata5, bon and cas exhibit dominant genetic interactions providing additional support that they function in the same pathway. Together, these data demonstrate that Gata5 plays multiple roles in endoderm development in zebrafish, and position Gata5 relative to other regulators of endoderm formation.

Gene amplification in PNETs/medulloblastomas: mapping of a novel amplified gene within the MYCN amplicon.

OBJECTIVES: The pathological entity of primitive neuroectodermal tumour/medulloblastoma (PNET/MB) comprises a very heterogeneous group of neoplasms on a clinical as well as on a molecular level. We evaluated the importance of DNA amplification in medulloblastomas and other primitive neuroectodermal tumours (PNETs) of the CNS. METHOD: Restriction landmark genomic scanning (RLGS), a method that allows the detection of low level amplification, was used. RLGS provides direct access to DNA sequences circumventing positional cloning efforts. Furthermore, we analysed several samples by CGH. DESIGN: Twenty primary medulloblastomas, five supratentorial PNETs, and five medulloblastoma cell lines were studied. RESULTS: Although our analysis confirms that gene amplification is generally a rare event in childhood PNET/MB, we found a total of 17 DNA fragments that were amplified in seven different tumours. Cloning and sequencing of several of these fragments confirmed the previous finding of MYC amplification in the cell line D341 Med and identified novel DNA sequences amplified in PNET/MB. We describe for the first time amplification of the novel gene, NAG, in a subset of PNET/MB. Despite genomic amplification, NAG was not overexpressed in the tumours studied. We have determined that NAG maps less than 50 kb 5' of DDX1 and approximately 400 kb telomeric of MYCN on chromosome 2p24. CONCLUSION: We found a similar but slightly higher frequency of amplification than previously reported. We present several DNA fragments that may belong to the CpG islands of novel genes amplified in a small subset of PNET/MB. As an example we describe for the first time the amplification of NAG in the MYCN amplicon in PNET/MB.

Measuring cognitive processes underlying picture naming in Alzheimer's and cerebrovascular dementia: a general processing tree approach.

Existing data from the Boston Naming Test were analyzed using standard statistical methods and with a General Processing Tree (GPT) model in an attempt to differentiate between patients with Alzheimer's Disease (AD) and Cerebrovascular dementia (CVD), matched for severity, and age-matched healthy controls. The GPT approach enables the estimation of parameters reflecting underlying cognitive processes (e.g., perceptual analysis, lexical access) based on categorical data. Compared to traditional analyses of proportion correct and of errors, the analysis with the GPT model was more sensitive in detecting differences between patient groups, as well as the source of these differences. Among the differences were two, evident in a comparison between very mild AD and very mild CVD patients: standard analyses did not reveal a significant difference between these groups; but the GPT analysis revealed that the CVD patients had significantly higher estimates than the AD patients on parameters reflecting lexical access and phonological realization.

The zebrafish bonnie and clyde gene encodes a Mix family homeodomain protein that regulates the generation of endodermal precursors.

Vertebrate endoderm development has recently become the focus of intense investigation. In this report, we first show that the zebrafish bonnie and clyde (bon) gene plays a critical early role in endoderm formation. bon mutants exhibit a profound reduction in the number of sox17-expressing endodermal precursors formed during gastrulation, and, consequently, a profound reduction in gut tissue at later stages. The endodermal precursors that do form in bon mutants, however, appear to differentiate normally indicating that bon is not required at later steps of endoderm development. We further demonstrate that bon encodes a paired-class homeodomain protein of the Mix family that is expressed transiently before and during early gastrulation in both mesodermal and endodermal progenitors. Overexpression of bon can rescue endodermal gene expression and the formation of a gut tube in bon mutants. Analysis of a newly identified mutant allele reveals that a single amino acid substitution in the DNA recognition helix of the homeodomain creates a dominant interfering form of Bon when overexpressed. We also show through loss- and gain-of-function analyses that Bon functions exclusively downstream of cyclops and squint signaling. Together, our data demonstrate that Bon is a critical transcriptional regulator of early endoderm formation.

A neurobehavioral approach for treatment of complex partial epilepsy: efficacy.

This is a retrospective study of the efficacy of a short-term comprehensive multidisciplinary neurobehavioral treatment approach for complex partial epilepsy. Eleven patients were treated intensively for five consecutive days followed by 6 months of weekly telephone contact and an additional 6 months of monitoring of seizure logs and journals. Data was analysed at least 24 months after initiation of treatment. Pre-treatment seizure frequency ranged from 1 to 15 per month. Post-treatment seizure frequency was zero per month for the nine patients who experienced less than four seizures per month prior to treatment and less than two per month for the other two patients. Additional benefits of the treatment program were improved levels of professional achievement in the arts and computer sciences and reduction of medication dosages.

A neurobehavioral treatment for unilateral complex partial seizure disorders: a comparison of right- and left-hemisphere patients.

This study looked at the efficacy of a multi-disciplinary neurobehavioral approach for treating patients with complex partial seizure disorders. Patients with a seizure focus in either the left or right hemisphere were compared for overall effectiveness of this approach in achieving control of complex partial seizures. Patients in this study received short-term treatment based on a model of self-control developed by the Andrews/Reiter Epilepsy Research Program. This research selected all patients who met the lateralization criterion from among cases receiving short-term treatment between 1992 and 1996. Forty-four patients were identified, a group of 21 right-hemisphere subjects and a second group of 23 left-hemisphere subjects. These patients were treated in a short-term (5 consecutive days) treatment protocol and then released, with weekly phone contact for 6 months following treatment. They were then followed for an additional 19 months through the continued submission of their seizure logs and journals. Subjects in both groups kept seizure records throughout the study starting with a two-month baseline period. Other data collected allowed study of the interaction of emotional states with seizure occurrence. This project produced valuable and relevant information regarding neurobehavioral management interventions as an effective adjunctive or alternative treatment for obtaining seizure control in epilepsy patients. Overall, 79% of patients treated achieved seizure control. More than 64% identified a recognizable emotional state that triggered seizures. The emotional trigger was specific for either the right or left hemisphere.

Primary and secondary locations of charge sites in angiotensin II (M + 2H)2+ ions formed by electrospray ionization.

High-energy tandem mass spectrometry and molecular dynamics calculations are used to determine the locations of charge in metastably decomposing (M + 2H)2+ ions of human angiotensin II. Charge-separation reactions provide critical information regarding charge sites in multiple charged ions. The most probable kinetic energy released (Tm.p.) from these decompositions are obtained using kinetic energy release distributions (KERDs) in conjunction with MS/MS (MS2), MS/MS/MS (MS3), and MS/MS/MS/MS (MS4) experiments. The most abundant singly and doubly charged product ions arise from precursor ion structures in which one proton is located on the arginine (Arg) side chain and the other proton is located on a distal peptide backbone carbonyl oxygen. The MS3 KERD experiments show unequivocally that neither the N-terminal amine nor the aspartic acid (Asp) side chain are sites of protonation. In the gas phase, protonation of the less basic peptide backbone instead of the more proximal and basic histidine (His) side chain is favored as a result of reduced coulomb repulsion between the two charge sites. The singly and doubly charged product ions of lesser abundance arise from precursor ion structures in which one proton is located on the Arg side chain and the other on the His side chain. This is demonstrated in the MS3 and MS4 mass-analyzed ion kinetic energy spectrometry experiments. Interestingly, (b7" + OH)2+ product ions, like the (M + 2H)2+ ions of angiotensin II, are observed to have at least two different decomposing structures in which charge sites have a primary and secondary location.

Gata5 is required for the development of the heart and endoderm in zebrafish.

The mechanisms regulating vertebrate heart and endoderm development have recently become the focus of intense study. Here we present evidence from both loss- and gain-of-function experiments that the zinc finger transcription factor Gata5 is an essential regulator of multiple aspects of heart and endoderm development. We demonstrate that zebrafish Gata5 is encoded by the faust locus. Analysis of faust mutants indicates that early in embryogenesis Gata5 is required for the production of normal numbers of developing myocardial precursors and the expression of normal levels of several myocardial genes including nkx2.5. Later, Gata5 is necessary for the elaboration of ventricular tissue. We further demonstrate that Gata5 is required for the migration of the cardiac primordia to the embryonic midline and for endodermal morphogenesis. Significantly, overexpression of gata5 induces the ectopic expression of several myocardial genes including nkx2.5 and can produce ectopic foci of beating myocardial tissue. Together, these results implicate zebrafish Gata5 in controlling the growth, morphogenesis, and differentiation of the heart and endoderm and indicate that Gata5 regulates the expression of the early myocardial gene nkx2.5.