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.

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.

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.

Apolipoprotein E in sporadic Alzheimer's disease: allelic variation and receptor interactions.

An increased prevalence of apolipoprotein E (ApoE) epsilon 4 allele exists in late onset familial Alzheimer's disease. We found, in sporadic Alzheimer's disease, that 62% of patients possessed an ApoE-epsilon 4 allele, compared with 20% of controls. ApoE-epsilon 4/4 patients had more senile plaques (SPs) than epsilon 3/3 patients. ApoE immunoreactivity of SPs was equivalent in both groups. Two receptors bind ApoE complexes, the low density lipoprotein (LDL) receptor and the LDL receptor-related protein (LRP). In normal brain, anti-LRP antibodies strongly stained neurons and lightly stained astrocytes; anti-LDL receptor antibodies stained only the neuropil and astrocytes. In Alzheimer's disease, SPs and reactive astrocytes were also strongly LRP immunoreactive. Colocalization of ApoE and LRP to SPs implies that these molecules may be involved in metabolism of components of SPs.

Glucagon immunoreactivities and amino acid profile in plasma of duodenopancreatectomized patients.

Glucogon immunoreactivity (IRG) was measured in plasma of duodenopancreatectomized subjects with a nonspecific (K-4023) and a specific (30-K) glucagon antiserum. After an overnight fast, plasma IRG (K-4023) was significantly (P < 0.05) higher in the subjects without pancreas, averaging 782+/-79 (SEM) pgeq/ml, than in the controls (482+/-80 pgeq/ml). IRG (30-K) of 162+/-68 pg/ml did not change during an infusion of arginine (450 mg/kg per 40 min). Insulin deprivation during 3 d in one patient did not restore the IRG response to arginine as reported in depancreatized dogs.Bio-Gel P-30 column chromatography revealed that virtually all IRG (30-K) measured in whole plasma was of different molecular weight than glucagon, and primarily of a mol wt >/= 40,000. Intravenous arginine did not significantly alter the chromatographic pattern of these plasmas. Thus, as postulated by others, duodeno-pancreatectomized humans have virtually no circulating 3,500-dalton glucagon. Hence, the presence of 3,500-dalton glucagon in plasma is not a condition for the diabetic state. It might, nevertheless, when present in normal or excessive amounts, worsen the metabolic state of diabetic patients. Among 14 amino acids measured in plasma of these patients, the concentrations of alanine, serine, ornithine, and arginine were significantly (P < 0.05) elevated to approximately twice that of normal: alanine and serine are both substrates for gluconeogenesis, whereas ornithine and arginine are involved in the formation of urea, the second product of hepatic gluconeogenesis. As the concentrations of branched chain amino acids were not grossly altered, it is hypothesized that this amino acid pattern is a consequence of glucagon deficiency rather than secondary to the diabetic state of these patients.

Physical mapping of the DDX1 gene to 340 kb 5' of MYCN.

One of the most important prognostic factors in neuroblastoma is amplification of the MYCN gene, which is strongly associated with advanced stages of disease and a poor prognosis. Although the MYCN amplicon sometimes spans more than 1 Mb, no other consistently expressed sequences from the MYCN amplicon have been reported. However, DDX1, a gene encoding a DEAD box protein, was recently mapped to chromosome 2p24 and is frequently co-amplified with MYCN. Therefore, we performed genomic mapping with YACs to determine the physical relationship between DDX1 and MYCN, and whether DDX1 was contained within the core region of amplification. Based on YAC restriction mapping and content analysis, DDX1 maps 340 kb 5' of MYCN, outside the core domain of consistent amplification. Interestingly, we also determined by sequence analysis and detailed restriction mapping that G21, previously isolated as a 'neuroblastoma-specific' cDNA clone from an MYCN amplicon, is a partial cDNA of DDX1. Our data confirm that DDX1 is amplified in some but not all MYCN-amplified tumors, and that it is rearranged in other cases. This suggests that the co-amplification of DDX1 is due to its proximity to MYCN.

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.

Effects of tumor necrosis factor-alpha on normal feline hematopoietic progenitor cells.

The effects of tumor necrosis factor-alpha (TNF-alpha) on feline bone marrow hematopoietic progenitors were evaluated by exposing bone marrow mononuclear cells from specific pathogen-free cats to different concentrations of TNF-alpha (ranging from 50 to 800 pg/ml) for 2 h before plating for clonal assays of colony-forming units. TNF-alpha caused a dose-dependent suppression of feline erythroid colony-forming units (CFU-E) and erythroid burst-forming units (BFU-E), whereas granulocyte-macrophage colony-forming units (CFU-GM) were minimally affected. TNF-alpha concentrations as low as 200 pg/ml significantly inhibited growth of erythroid progenitors. Addition of polyclonal rabbit anti-TNF-alpha antibodies completely neutralized the suppressive effect of TNF-alpha on erythroid progenitors. At higher concentrations of TNF-alpha (800 pg/ml), 35% of CFU-E and 21% of BFU-E still survived, indicating that some erythroid progenitors are not sensitive to a single exposure of TNF-alpha in vitro. These results suggest that TNF-alpha may play a role in regulating hematopoiesis in cats and may be involved in the pathogenesis of erythroid aplasia in cats infected with feline leukemia virus.

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.

Extracellular signal-regulated kinase (MAP kinase) immunoreactivity in the rhesus monkey brain.

Extracellular signal regulated kinases (ERKs) are a recently cloned family of genes that encode the MAP kinase protein kinases. They are highly expressed in brain and are believed to play an integral role in neural cellular responses to receptor activation. A role for ERKs has been postulated in Alzheimer's disease, where they have been implicated in phosphorylation of tau in neurofibrillary tangles. We explored the neuroanatomic distribution of ERK immunoreactivity in the rhesus monkey brain. The hippocampal formation, especially the mossy fiber zone and the molecular layer of the dentate gyrus are the most heavily immunostained areas. Cerebral cortex is, in general, more intensely stained in the supragranular layers. The caudate, putamen, and substantia nigra contain more immunoreactivity than the claustrum, globus pallidus, or thalamus with the exception of midline thalamic structures. These results suggest a marked regional and laminar distribution of ERKs in the primate brain.

Cognitive-behavioral body image therapy for body dysmorphic disorder.

Body dysmorphic disorder (BDD) is a distressing body image disorder that involves excessive preoccupation with physical appearance in a normal appearing person. Prior case reports of behavior therapy were encouraging, but no controlled evaluation of behavior therapy or any other type of treatment had been conducted. In the present study, 54 BDD subjects were randomly assigned to cognitive behavior therapy or no treatment. Patients were treated in small groups for eight 2-hour sessions. Therapy involved modification of intrusive thoughts of body dissatisfaction and overvalued beliefs about physical appearance, exposure to avoided body image situations, and elimination of body checking. Body dysmorphic disorder symptoms were significantly decreased in therapy subjects and the disorder was eliminated in 82% of cases at posttreatment and 77% at follow-up. Overall psychological symptoms and self-esteem also improved in therapy subjects.

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.

Cooperative ligand-lattice binding. Approximate Gaussian binding distribution.

Nearest-neighbor cooperative binding of a ligand covering n sites and binding with equilibrium constant K and cooperativity factor omega to a large molecule with m binding sites (m much greater than n omega, n/omega) can be approximately described by a Gaussian distribution P(q-qmax), where q is the number of ligands bound and qmax the most probable value of q. The variance of the Gaussian is equal to the derivative dqmax/d ln(L), where L is the free ligand concentration. This variance, sigma 2, is a complicated function of qmax. However, in the limits of very large cooperativity, omega much greater than 1, very large anticooperativity, omega much less than 1, or noncooperativity, omega = 1, simpler expressions for sigma 2 can be given. For qmax = m/(n + 1), where the most probable number of bound ligands equals the number of free binding sites, sigma 2 has a particularly simple form: sigma 2 = 2m omega 1/2/(n + 1)3. The Gaussian and the infinite lattice approximations for the average number of ligands bound are good approximations only if sigma is much smaller than the number of binding sites. The variance may therefore provide an easy check on the validity of the infinite lattice approximation, which is commonly used to analyze experimental binding data.

Development of the body dysmorphic disorder examination.

The Body Dysmorphic Disorder Examination (BDDE) is a semi-structured clinical interview designed to diagnose body dysmorphic disorder and to measure symptoms of severely negative body image. It tape into preoccupation with and negative evaluation of appearance, self-consciousness and embarrassment, excessive importance given to appearance in self-evaluation, avoidance of activities, body camouflaging, and body checking. The BDDE had adequate internal consistency and test-retest and interrater reliability. It correlated with measures of body image, negative self-esteem, and psychological symptoms, and was sensitive to change following treatment of body dysmorphic disorder. The BDDE distinguished body dysmorphic disorder patients from clinical and non-clinical control subjects and agreed with other clinicians' diagnosis of body dysmorphic disorder. The BDDE provided unique information in predicting clinical status when controlling for psychological adjustment and other measures of body image.

Assessment of body image in eating disorders with the body dysmorphic disorder examination.

The Body Dysmorphic Disorder Examination (BDDE) has several advantages for the assessment of body image in eating disorder patients. It measures distressing self-consciousness, preoccupation with appearance, overvalued ideas about the importance of appearance to one's self-worth, and body image avoidance and checking behaviors. The BDDE is relevant for any type of appearance complaint and is not limited to weight or body shape concerns. The BDDE measures the useful targets for body image therapy. In a sample of eating disorder patients, the Body Dysmorphic Disorder Exam had good internal consistency and was significantly correlated with other measures of body image. It added new information to the discrimination of women with eating disorders from clinical and nonclinical controls beyond that provided by other measures of body image.

A multinomial modeling analysis of memory deficits in Alzheimer's disease and vascular dementia.

Data from the immediate recall task of the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological test battery were disaggregated into nine subject groups and analyzed with traditional statistics as well as with a general processing tree (GPT) model of free recall. The groups represented four levels of severity of Alzheimer's and vascular dementia, as well as a ninth group of healthy elderly controls. It was demonstrated that the patterns of success and failure of recall to individual items across successive trials contained much more information than the marginal trial-to-trial performance scores traditionally used in scoring the test. The GPT model analyzed recall performance in terms of three levels of item storage: unstored, intermediate, and long-term. Associated with the intermediate and long-term storage levels were respective retrieval parameters. Statistical methods enable one to estimate the parameters for each group, and the analyses revealed group differences in long-term storage that were not evident in a statistical analysis of the marginal trial-to-trial performance scores.

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.