Myositis Ossificans Traumatica of Bilateral Sternocleidomastoid Muscles After Chiropractor Adjustment: A Case Report.

A woman in her 20s with a past medical history of surgical debulking of a right neck mass presented to the hospital for persistent and worsening right shoulder pain. The shoulder pain was associated with trismus and back and neck pain. A CT scan of the neck with contrast revealed post-surgical changes with increased heterotopic ossification throughout the surgical site extending to the supraclavicular soft tissues and the left sternocleidomastoid muscle, suggesting muscle ossification. A biopsy was performed, and the patient was diagnosed with myositis ossificans (MO). Initial treatment began with the administration of steroids and analgesics. She was scheduled for a follow-up with orthopedics, rheumatology, and genetics, but she was lost for follow-up. MO is a very rare medical condition usually associated with trauma, and in our patient, the symptoms started after a chiropractic adjustment.

Extraskeletal Ewing Sarcoma: A Case Report.

Ewing sarcoma is one of the most common primary bone tumors arising from neuroectodermal cells mainly presenting in the younger population. Instances of this highly malignant tumor manifesting outside of the bone and outside of the typical age range create an unfamiliar clinical scenario. In this report, we present a rare extraskeletal Ewing sarcoma in a 42-year-old woman with a subcutaneous soft tissue mass in the posterior chest displaying a positive EWSR1 gene rearrangement via fluorescence in situ hybridization. The patient is currently on a chemotherapy regimen showing favorable response to the tumor size despite additional complications. This overall presentation of Ewing sarcoma allows further understanding of the malignancy and fosters better care for future cases.

Improved radioimmunodetection of carcinomas with a re-injection of monoclonal antibodies after formation of anti-mouse antibodies.

Scintigraphic imaging was satisfactory in animal experiments, i.e., in the radioimmunodetection with 125J anti-tissue polypeptide antigen monoclonal antibodies and implanted HELA cell carcinomas. Unlabeled anti-mouse antibodies (AMAB), in a surplus of 40:1, 200:1 and 4000:1 compared to the radioactive antibody, were administered five days after administering the 125I anti-TPA antibody (RAAB). In immunoscintigraphies, radioactivity accumulated in the liver immediately after administering the secondary antibody, and the tumor's imaging worsened. It can be expected that imunoscintigraphic imaging might improve when radioimmunodetection is re-performed after the formation of human anti-mouse antibodies (AMAB) and when the ratio of the primary to the secondary antibody is nearly equivalent because, in this ratio, the formation of immune complexes might be accelerated. It is possible to measure the quantity of formed anti-mouse antibodies (AMAB) with immunography measurements. A second administration of diagnostic or therapeutic monoclonal antibodies might lead to the formation of immune complexes if the quantities of the monoclonal antibodies and the anti-mouse antibodies have an equivalent ratio. A second performance of the radioimmunodetection four to eight weeks after the first radioimmunodetection can achieve better tumor imaging because human anti-mouse antibodies (AMAB) can be formed. Immune complexes of the radioactive antibody and the human anti-mouse antibody (AMAB) can be formed to concentrate radioactivity in the tumor.

Copper nitrite reductase from Sinorhizobium meliloti 2011: Crystal structure and interaction with the physiological versus a nonmetabolically related cupredoxin-like mediator.

We report the crystal structure of the copper-containing nitrite reductase (NirK) from the Gram-negative bacterium Sinorhizobium meliloti 2011 (Sm), together with complex structural alignment and docking studies with both non-cognate and the physiologically related pseudoazurins, SmPaz1 and SmPaz2, respectively. S. meliloti is a rhizobacterium used for the formulation of Medicago sativa bionoculants, and SmNirK plays a key role in this symbiosis through the denitrification pathway. The structure of SmNirK, solved at a resolution of 2.5 Å, showed a striking resemblance with the overall structure of the well-known Class I NirKs composed of two Greek key ß-barrel domains. The activity of SmNirK is ~12% of the activity reported for classical NirKs, which could be attributed to several factors such as subtle structural differences in the secondary proton channel, solvent accessibility of the substrate channel, and that the denitrifying activity has to be finely regulated within the endosymbiont. In vitro kinetics performed in homogenous and heterogeneous media showed that both SmPaz1 and SmPaz2, which are coded in different regions of the genome, donate electrons to SmNirK with similar performance. Even though the energetics of the interprotein electron transfer (ET) process is not favorable with either electron donors, adduct formation mediated by conserved residues allows minimizing the distance between the copper centers involved in the interprotein ET process.

Risk Genes in Schizophrenia and Their Importance in Choosing the Appropriate Antipsychotic Treatment.

BACKGROUND: Schizophrenia is a chronic mental illness that in 80% of cases has a genetic etiology. In the last years, 260 risk genes with a predisposition to schizophrenia have been discovered and correlations between risk genes and the therapeutic efficacy of an antipsychotic treatment/pharmacotherapy resistance have been reported. OBJECTIVE: The objective of this review is to update the main risk genes involved in schizophrenia and to establish an association between the single nucleotide polymorphisms (SNPs) of these genes and pharmacotherapy resistance/efficacy of a determined antipsychotic treatment. Besides, neural networks in the brain centers involved in schizophrenia will be updated to point out the altered functions of classical neurotransmitters and neuropeptides due to risk genes. METHODS: In schizophrenia, important risk genes, such as catechol-O-methyl transferase (COMT), monoamine oxidase (MAO A/B), glutamic acid decarboxylase 67 (GAD 67), dysbindin-1 and neuregulin-1 will be mentioned. To describe the function of these risk genes, neural networks in the ventral tegmental area, hippocampus and prefrontal cortex will also be developed. RESULTS: An association between the SNPs of some risk genes and the efficacy of an antipsychotic treatment is reported: SNPs such as rs165599 (COMT gene), rs1801028 (D2 receptor gene) and rsSer9Gly (D3 receptor gene) are associated with a better antipsychotic treatment efficacy (e.g., treatment of negative schizophrenic symptoms with risperidone). The rs4680 SNP (COMT and D2 receptor genes) is associated with antipsychoticinduced dopamine hypersensitivity and pharmacotherapy resistance. The function of risk genes is described: COMT and MAO A/B genes, with reduced activity in the corresponding enzymes, are associated with a decrease in dopamine degradation and hence dopamine hyperactivity occurred via D2 receptors. The GAD 67 risk gene is linked with GABAergic dysfunction and consequently GABAergic neurons weakly presynaptically inhibit D2 dopaminergic neurons. The D-amino acid oxidase activator (DAOA) risk gene is connected with glutamatergic dysfunction via NMDA receptors. Glutamatergic neurons might exert a weak presynaptic inhibition upon 5- HT2A serotonergic neurons located in the ventral tegmental area and hippocampus. Neural networks in the latter two regions and in the prefrontal cortex are updated. CONCLUSION: It is important to examine the SNPs of the risk genes involved in schizophrenia to establish a correlation between these SNPs and the efficacy of a determined antipsychotic drug. In the future, after examining these SNPs, it might be possible to choose the most appropriate antipsychotic drug. Thus, schizophrenic patients with a good response to a determined antipsychotic treatment and patients with resistance to this treatment could be well differentiated.

[On Statistical Underreporting of Norovirus-Infections: Insights from Register Data of Two Local Public Health Authorities]. / Zur statistischen Untererfassung von Norovirus-Infektionen: Erkenntnisse aus Daten von zwei Gesundheitsämtern.

BACKGROUND: Only laboratory-confirmed norovirus (NoV) cases have to be notified to the Robert Koch Institute (RKI) since 2011, but not other, e. g. clinical-epidemiological cases. It can be assumed that the extent of underreporting of NoV cases in Germany has significantly increased since then. OBJECTIVES: To discuss the extent of underreporting, we wanted to find out how many laboratory tests were carried out during gastroenteritis outbreaks. Furthermore, the significance of NoV outbreaks in occupational health is discussed. MATERIALS AND METHODS: Of all pseudonymized gastroenteritis outbreak data reported to 2 local health authorities between 2011 and 2015, the proportion of NoV outbreaks and reported cases of infection among employees in hospitals and community facilities (nursing homes for the elderly, day-care centers, schools) confirmed by laboratory tests was calculated retrospectively. RESULTS: Only a few gastroenteritis outbreaks in day-care centers were etiologically diagnosed, so that only 6% and less could be classified as NoV outbreaks. In nursing homes for the elderly, about half of the outbreaks were classified as NoV, in hospitals almost all of them. Employees accounted for up to 23% of those affected in NoV outbreaks. CONCLUSIONS: The low level of laboratory diagnostics carried out during gastroenteritis outbreaks in day-care centers suggests a considerable number of hidden NoV cases. The significant proportion of staff relative to the total number of infected persons during the outbreaks highlights the importance of the burden of NoV outbreaks as a topic in occupational health. Further, large-scale prospective studies are needed to empirically substantiate these initial findings.

The Novel Antipsychotic Drug Cariprazine and Cognition Enhancing Drugs: Indications for their Use as the Add-on Therapy in Schizophrenia.

BACKGROUND: Schizophrenia and schizoaffective disorder are treated with antipsychotic drugs. Some patients show treatment-resistant forms of psychotic disorders, and in this case, they can be treated with clozapine. Based on the previous reviews on novel antipsychotic drugs, it is important to know whether the add-on therapy with the new drugs can ameliorate the positive and negative schizophrenic scale (PANSS) total score. OBJECTIVES: The aim of this review is to suggest an appropriate treatment for patients with treatment-resistant forms of psychotic disorders. A combination of the currently available antipsychotic drugs with novel antipsychotic or modulating drugs might improve negative schizophrenic symptoms and cognitive function and thereby social functioning and quality of life. RESULTS: The mechanisms of action, the therapeutic effects, and the pharmacokinetic profiles of novel antipsychotic drugs such as cariprazine, brexipiprazole, and lumateperone have been updated. Published case reports of patients with treatment-resistant psychoses have also been discussed in this study. These patients were treated only with clozapine, as a result of which a high PANSS total score was observed. Only the add-on therapy with cariprazine improved the score, and above all, the negative schizophrenic symptoms and cognitive functions were improved. For the ensurance of a constant antipsychotic drug concentration, long-acting injectable antipsychotic drugs might be a choice for the maintenance therapy in schizophrenia. New modulating drugs, such as receptor positive allosteric modulators (N-methyl-D-aspartate receptor; subtype 5 of the metabotropic glutamatergic receptor) and encenicline, an alpha7 nicotinic cholinergic receptor agonist, have been investigated in preclinical and clinical trials. CONCLUSION: In clinical trials, patients with treatment-resistant forms of psychosis should be examined to know whether combination therapy with clozapine and a novel antipsychotic drug can ameliorate the PANSS total score. In schizophrenia, long-acting injectable antipsychotic drugs are safe and tolerable maintenance therapy. In further clinical studies, it should be investigated whether patients with treatment-resistant forms of psychoses can improve negative schizophrenic symptoms and cognitive functions by the add-on therapy with cognitionenhancing drugs.

Significance of norovirus in occupational health: a review of published norovirus outbreaks in Central and Northern Europe.

OBJECTIVES: Globally, norovirus (NoV) is the leading cause of gastroenteritis infection among all ages. The development of prevention strategies in the field of occupational health requires a detailed knowledge about the impact of the disease on employees. This review article aims not only at evaluating the burden of NoV outbreaks on staff but also at discussing implications for future prevention strategies. METHODS: Published NoV outbreaks in Central and Northern Europe were identified via a systematic literature search. Additionally, published NoV outbreaks in Germany were detected via a manual literature search. Key epidemiological data, as the number of symptomatic staff, was then extracted. The proportion of affected employees was calculated for each dataset (single NoV outbreaks or aggregated data of multiple outbreaks). RESULTS: Overall, 116 datasets were extracted from 72 relevant articles. 144,852 persons were affected by NoV gastroenteritis, 25,408 out of them (17.5%) were employees. 23,874 (94.0%) of them fell sick during outbreaks in hospitals and related settings. NoV cases among personnel in food establishments were reported only sporadically (mean ratio: 0.01). CONCLUSIONS: Employees in hospitals and community facilities seem quantitatively to be most vulnerable towards NoV epidemics. Therefore, high quality of prevention measures in these settings, respective compliance with prevention strategies should have the highest priority. The disease can be considered as an occupational disease, even regularly without long-term consequences. Following work safety rules, a vaccination for vulnerable groups should be recommended if the vaccine development turns out to be successful.

Challenges in Infection Epidemiology: On the Underreporting of Norovirus Gastroenteritis Cases in Germany.

It is commonly accepted that the number of officially reported incidences of norovirus (NoV) according to the German Protection against Infection Act (Infektionsschutzgesetz) does not reflect the 'true' incidence of NoV in Germany. This study aims to reveal the reasons for the underreporting of NoV cases by comparing secondary data. METHODS: NoV incidence (cases per 100,000 reference persons) in the age group 18-65 was derived from register data of four different sources in the German public health system (2011-2015): Statutory health insurance in the federal state of Lower Saxony (AOK; in- and outpatient cases), the Research Institute of Ambulatory Health Care in Germany (ZI; outpatient cases), the German Federal Statistical Office (inpatient cases; DESTATIS), and the Robert Koch Institute (RKI SurvStat; health reporting data). RESULTS: the incidence derived from the AOK in Lower Saxony varied between 49 and 66 NoV cases per 100,000 persons and was thus lower than at the federal level. Incidences of all inpatient and outpatient data were lower than the incidence according to the RKI in the last 2-3 years of the observation period. CONCLUSIONS: the disagreement between NoV incidences calculated from secondary inpatient and outpatient data and the respective numbers published by the RKI can be regarded as an indication that not all NoV cases were reported to public health authorities. This might be due to missed cases during the notification procedure or misclassification of gastroenteritis cases by general practitioners. Considering the limitations associated with analyzing secondary data, the appropriateness of these assumptions should be verified in future studies.

Surgical Smoke-Hazard Perceptions and Protective Measures in German Operating Rooms.

(1) Background: Hazardous substances in surgical smoke that is generated during laser or electrosurgery pose a potential health hazard. In Germany, the Technical Rules for Hazardous Substances (TRGS 525) have included recommendations for appropriate protective measures since 2014. Up to now, no empirical data has been available on the extent to which recommendations have been implemented in practice. (2) Methods: In 2018, 7089 surgeons in hospitals and outpatient practices were invited by email to participate in an online survey. In addition, 219 technical assistants were interviewed. The questionnaire dealt with knowledge of, and attitudes toward, the hazard potential of surgical smoke, as well as the availability and actual use of protective measures. Furthermore, manufacturers and distributors of smoke extraction devices were asked to give their assessment of the development of prevention in recent years. (3) Results: The survey response rate was 5% (surgeons) and 65% (technical assistant staff). Half of all surgeons assumed that there were high health hazards of surgical smoke without taking protective measures. Operating room nurses were more often concerned (88%). Only a few felt properly informed about the topic. The TRGS recommendations had been read by a minority of the respondents. In total, 52% of hospital respondents and 65% of the respondents in outpatient facilities reported any type of special suction system to capture surgical smoke. One-fifth of respondents from hospitals reported that technical measures had improved since the introduction of the TRGS 525. Fifty-one percent of the surgeons in hospitals and 70% of the surgeons in outpatient facilities "mostly" or "always" paid attention to avoiding surgical smoke. The most important reason for non-compliance with recommendations was a lack of problem awareness or thoughtlessness. Twelve industrial interviewees who assessed the situation and the development of prevention in practice largely confirmed the prevention gaps observed; only slight developments were observed in recent years. (4) Conclusions: The low response rate among surgeons and the survey results both indicate a major lack of interest and knowledge. Among other measures, team interventions with advanced training are needed in the future.

Therapeutic Effect of Novel Antidepressant Drugs Acting at Specific Receptors of Neurotransmitters and Neuropeptides.

BACKGROUND: Major depression is a frequent psychiatric disease. One- third of the depressive patients remain treatment-resistant; thus, it is urgent to find novel antidepressant drugs. OBJECTIVE: In major depression, in several brain areas the neural networks involved and the alterations of neurotransmitters and neuropeptides are updated. According to these networks, new pharmacological agents and effective combinations of antidepressant drugs achieving a more efficacious antidepressant treatment are suggested. RESULTS: In the neural networks, the prefrontal cortex has been included. In this brain area, glutamatergic neurons, which receive an activating potential from D2 dopaminergic neurons, presynaptically inhibit M1 muscarinic cholinergic neurons via NMDA receptors. Medium spiny GABAergic/somatostatin neurons, which receive projections from M1 muscarinic cholinergic neurons, presynaptically inhibit D2 dopaminergic neurons via GABAA/somatostatin1 receptors. The combination of an NMDA receptor antagonist with an M1 muscarinic cholinergic receptor antagonist can achive a rapid, long-lasting antidepressant effect. CONCLUSION: In preclinical studies, the antidepressant effect of orvepitant, an NK1 receptor antagonist, has been demonstrated: this antagonist reaches a complete blockade of NK1 receptors. In clinical studies, the combination of an NMDA receptor antagonist with an M1 muscarinic cholinergic receptor antagonist should be investigated indepth as well as the therapeutic effect of orvepitant. In clinical studies, the antidepressant effect of a triple reuptake inhibitor should be examined and compared to current antidepressant drugs.

Neural Networks in Generalized Epilepsy and Novel Antiepileptic Drugs.

BACKGROUND: In previous works, alterations of neurotransmitters and neuropeptides in the brain areas involved in generalized epilepsy have been reported. OBJECTIVE: We reviewed the alterations of these neurotransmitters and neuropeptides in the following brain areas involved in generalized epilepsy: hippocampus, hypothalamus, thalamus and cerebral cortex. In these brain areas, the neural networks are also actualized. The mechanisms of action of newer antiepileptic drugs in the treatment of generalized epilepsy are also discussed. RESULTS: Up-dating the neurotransmitter and neuropeptide alterations, we found that hippocampal GABAergic neurons presynaptically inhibit epileptogenic neurons via GABAB receptors. Epilepsy modulating neuropeptides (galanin, neuropeptide Y, dynorphin) are also involved. GABA deficiency, serotonin hyperactivity, dopamine hyperactivity and glutamate excitotoxicity can enhance ictogenesis: neurons containing these neurotransmitters form the main neural circuit. An increased excitability occurs when the alteration of these neurotransmitters is permanent. CONCLUSION: In preclinical studies, the GABAB receptor agonist GS 39,783 exerted a good antiepileptic effect. Perampanel, an AMPA receptor antagonist, showed good clinical effects in the treatment of partial-onset seizures and primary generalized tonic-clonic seizures. In this treatment, perampanel can be combined with other antiepileptic drugs. Brivaracetam, which shows a high affinity for the synaptic vesicle 2A, exerted a good efficacy in the treatment of adult focal seizures and secondarily generalized tonic-clonic seizures.

A three-domain copper-nitrite reductase with a unique sensing loop.

Dissimilatory nitrite reductases are key enzymes in the denitrification pathway, reducing nitrite and leading to the production of gaseous products (NO, N2O and N2). The reaction is catalysed either by a Cu-containing nitrite reductase (NirK) or by a cytochrome cd 1 nitrite reductase (NirS), as the simultaneous presence of the two enzymes has never been detected in the same microorganism. The thermophilic bacterium Thermus scotoductus SA-01 is an exception to this rule, harbouring both genes within a denitrification cluster, which encodes for an atypical NirK. The crystal structure of TsNirK has been determined at 1.63 Šresolution. TsNirK is a homotrimer with subunits of 451 residues that contain three copper atoms each. The N-terminal region possesses a type 2 Cu (T2Cu) and a type 1 Cu (T1CuN) while the C-terminus contains an extra type 1 Cu (T1CuC) bound within a cupredoxin motif. T1CuN shows an unusual Cu atom coordination (His2-Cys-Gln) compared with T1Cu observed in NirKs reported so far (His2-Cys-Met). T1CuC is buried at ∼5 Šfrom the molecular surface and located ∼14.1 Šaway from T1CuN; T1CuN and T2Cu are ∼12.6 Šapart. All these distances are compatible with an electron-transfer process T1CuC → T1CuN → T2Cu. T1CuN and T2Cu are connected by a typical Cys-His bridge and an unexpected sensing loop which harbours a SerCAT residue close to T2Cu, suggesting an alternative nitrite-reduction mechanism in these enzymes. Biophysicochemical and functional features of TsNirK are discussed on the basis of X-ray crystallography, electron paramagnetic resonance, resonance Raman and kinetic experiments.

Cardiac and autonomic function in patients with Wilson's disease.

BACKGROUND: The clinical effect of copper accumulation on the heart of patients suffering from Wilson's disease (WD) is not completely understood. We aimed to determine if patients with WD show signs of cardiac involvement, structural heart disease or autonomic dysfunction. In this prospective trial, we studied 61 patients (mean age 44.3 ± 15.2 years, 51% males) with WD and compared them to 61 age- and gender-matched healthy controls. All subjects underwent clinical examination, blood tests, echocardiography and 24 h electrocardiographic (ECG) recording. RESULTS: Left- and right ventricular systolic function did not differ significantly between WD patients and controls. However, 5 of the 61 patients had a reduced left ventricular ejection fraction (LVEF). Furthermore, diastolic dysfunction was more prevalent in WD patients (9 of 61 vs. 0 of 61, p = 0.001). The severity of WD based on the Unified Wilson's Disease Rating Scale was significantly correlated to NT-pro BNP (r = 0.34, P = 0.013). Patients with an exacerbation of WD in medical history had higher troponin levels compared to those without (11.3 ± 4.7 vs 4.6 ± 1.2). The autonomic function assessed by triangular index (TI) and SDNN-index was significantly reduced in WD patients compared to controls in most in almost every age category (p-value TI and SDNN: age 20-29, p < 0.001 and 0.05; age 30-39, p < 0.01 and not significant (ns); age 40-49, p < 0,01 and 0.001; age 50-59, p = ns and < 0.001, age 60-70, p < 0.05 and ns). CONCLUSION: Our data demonstrate that cardiac involvement and autonomic dysfunction in WD is possible, however the underlying cause is still not known. We suggest that patients with signs and symptoms of structural heart disease should be examined by a cardiologist in addition to the interdisciplinary treatment team of WD.

Characterization of solid and vapor products from thermochemical conversion of municipal solid waste woody fractions.

The ever-increasing consumption of material goods with economic growth is resulting in an increasing generation of municipal solid waste (MSW) and the rapid filling of landfills. Fractions of municipal solid waste containing wood-based products have the potential to be used for the development of value added products. In this paper we produced and characterized biochar and pyrolysis vapors from municipal solid waste (MSW) woody fractions to demonstrate their suitability towards soil amendments. Carbonization work focused on compost overs, molded wood pallets, treated wood, sawmill cut ends, wood derived fuels, furniture, painted wood, plywood, oriented strand board and particle boards from Washington State recycling facilities. The goal of this research is to use these biochars as soil amendments; however, there are concerns with both the potential presence of condensed organic pollutants and trace metals. The presence of trace metals and polycyclic aromatic hydrocarbons (PAH) in all the biochars produced were examined. GC-MS analyses of liquid extracts did not reveal the presence of soluble PAH compounds. High concentrations of mercury (Hg) and arsenic (As) were found in the biochar made from painted wood and treated wood, respectively. Among the methods tested for the removal of trace metals, acid washing was found to be the most effective. The volatiles released from the analyzed MSW fractions were also analyzed in Py-GC-MS studies. Among these volatile compounds, many contained Cl, N, or S, which could be potential sources of pollution if the pyrolysis vapors are combusted.