Miscellaneous Group Research Articles

Two Notes on the Collection of Greek Ritual Norms Looking Back, Looking Forward

Launched in 2017, the Collection of Greek Ritual Norms provides an open-access commentary on selected ancient Greek inscriptions which define parameters of ritual practice. These short notes address two issues superficially concerning the name of the Collection of Greek Ritual Norms, but more deeply engaging with what one means by the notion of 'ritual norm' and what one implies in considering such norms 'Greek'. A term like 'cult regulation' might conveniently be used to replace the misnomer 'sacred law', but this encompasses a similarly broad and miscellaneous group of inscriptions. By contrast, the category of 'ritual norm' aims to reframe the discussion by focussing on normativity – paradigms and exceptions – with regard to two key rituals, sacrifice and purification. It thus only partly reprises the corpus of 'sacred laws', while also including other inscriptions or excerpts from them. Calling such norms 'Greek' is not intended as an 'ethnic' designation of the rituals they describe but rather as a reference to the language of the inscriptions. The label 'Greek ritual norms' is thus programmatic, allowing for a wider investigation of the normative characteristics of rituals within the religious 'middle grounds' of the ancient Greek world.

Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer

BackgroundCpG Island Methylator Phenotype (CIMP) is an epigenetic phenotype in CRC characterized by hypermethylation of CpG islands in promoter regions of tumor suppressor genes, leading to their transcriptional silencing and loss of function. While the prevalence of CRC differs across geographical regions, no studies have compared prevalence of CIMP-High phenotype across regions. The purpose of this project was to compare the prevalence of CIMP across geographical regions after adjusting for variations in methodologies to measure CIMP in a meta-analysis.MethodsWe searched PubMed, Medline, and Embase for articles focusing on CIMP published from 2000 to 2018. Two reviewers independently identified 111 articles to be included in final meta-analysis. We classified methods used to quantify CIMP into 4 categories: a) Classical (MINT marker) Panel group b) Weisenberg-Ogino (W-O) group c) Human Methylation Arrays group and d) Miscellaneous group. We compared the prevalence of CIMP across geographical regions after correcting for methodological variations using meta-regression techniques.ResultsThe pooled prevalence of CIMP-High across all studies was 22% (95% confidence interval:21–24%; I2 = 94.75%). Pooled prevalence of CIMP-H across Asia, Australia, Europe, North America and South America was 22, 21, 21, 27 and 25%, respectively. Meta-regression analysis identified no significant differences in the prevalence of CIMP-H across geographical regions after correction for methodological variations. In exploratory analysis, we observed variations in CIMP-H prevalence across countries.ConclusionAlthough no differences were found for CIMP-H prevalence across countries, further studies are needed to compare the influence of demographic, lifestyle and environmental factors in relation to the prevalence of CIMP across geographical regions.

Rituximab-associated Hypogammaglobulinemia in pediatric patients with autoimmune diseases

BackgroundDespite the increased use of rituximab in treating pediatric patients with autoimmune diseases in the last decade, there are limited data on rituximab safety in those subjects who have a developing immune system. The objective of this study is to determine the prevalence of hypogammaglobulinemia in children with autoimmune disease receiving rituximab within the first three years of treatment in the pediatric rheumatology clinic at a tertiary care center.MethodsWe conducted a retrospective chart review of 63 pediatric subjects who received rituximab for the treatment of their autoimmune disease. Immunoglobulin gamma (IgG) levels, immunosuppressive medication and the need for immunoglobulin replacement therapy were evaluated. Hypogammaglobulinemia was defined as a serum IgG level less than two standard deviations below the mean for age-matched healthy controls.ResultsTwenty-eight patients (44%) were found to have hypogammaglobulinemia. Hypogammaglobulinemia occurred within the first six months of rituximab treatment in the majority of patients (22 out of 28). The occurrence of hypogammaglobulinemia varied based on the rituximab indication: 46% pediatric Systemic Lupus Erythematosus (SLE), 71% autoimmune CNS disease, 60% ANCA vasculitis, and 12% in the miscellaneous group. Autoimmune CNS disease had more severe hypogammaglobulinemia, more persistent and was associated with more frequent or severe infections. Three patients with autoimmune CNS disease and one with SLE were given IgG replacement therapy to prevent recurrent or severe infections.ConclusionsThe prevalence of hypogammaglobulinemia in rituximab treated children with autoimmune disease seems to be higher than published data for adults, especially for children with autoimmune CNS disease. The onset of hypogammaglobulinemia is usually within six months of initiation of rituximab therapy. We recommend: 1) obtaining an IgG level prior to starting rituximab; 2) close monitoring for hypogammaglobulinemia after the use of rituximab in pediatric patients and 3) early institution of immunoglobulin replacement therapy if patients develop recurrent infections.

The increasing prominence of "non-surgical" articles in surgical literature.

Publications in the surgical field have usually to do with technical skills (TS). However, the field peripheral to surgical procedures, which brings to bear non-technical skills (NTS) has been achieving increasing prominence. The goal of this study is to objectively assess the evolution of the two fields in surgical literature. The authors perused all the articles published over a decade in four large-scale surgical journals and assigned them to the following three categories: (1) TS, (2) NTS or (3) miscellaneous. While the "TS group" included all aspects of surgical procedures, the "NTS group" comprised all aspects of non-surgical perioperative management, and the "miscellaneous group" was composed of all elements extraneous to the first two fields. Of the 8775 articles analyzed, 4326 (49%) belonged to the TS group, 2343 (27%) to the NTS group and 2138 (24%) to the miscellaneous group. There was a significant decrease in the proportion of TS publications [61% in 2007, 44% in 2016 (P<0.001)], accompanied by a significant increase in the proportion of NTS publications (16% in 2007, 34% in 2016 (P<0,001)] over the course of the last decade. The trend first appeared in 2009 and has been confirmed and reinforced over the ensuing years. The increasing prominence of non-surgical skills represents a major shift in the editorial choices of high impact surgical journals. It highlights the extent to which the surgical community is manifesting increased interest in the perioperative field, which is now drawing almost as much attention as surgical procedure per se.

Prevalence of Hypovitaminosis D in Patients Visiting a Tertiary Care Center in Chitwan, Nepal

Background: As documented by a large body of evidences, Hypovitaminosis D prevails both in the general and the hospitalized populations. We conducted this study to determine the prevalence of hypovitaminosis D amongst the patients visiting a tertiary care hospital and compare the rate gender-wise, across different categories of socio-demographic variables.&#x0D; Methods: It was a cross-sectional study (retrospective chart review) based on the hospital registry of patients at College of Medical Sciences and Teaching Hospital, Bharatpur, Chitwan, Nepal. From the registry, we retrieved the socio-demographic variables (age, gender, ethnicity and season) along with serum vitamin D (25-hydroxy-cholecalciferol) concentrations of the study subjects from January 2015 to August 2018, for our analysis. Hypovitaminosis D was defined as serum vitamin D &lt;30 ng/mL (insufficiency: 20-30ng/mL and deficiency: &lt;20 ng/mL).&#x0D; Results: The overall prevalence of hypovitaminosis D was 70.7% (insufficiency: 35.9% and deficiency: 34.8%), 72.4% (females), 64.2% (males), 76.3% (first age-quartile), 74.5% (miscellaneous ethnic group), and 73.9% (Spring). Females had higher prevalence rates of hypovitaminosis D (and lower median serum 25-hydroxy-cholecalciferol lev-els) as compared to males, in overall participants, and those under each category of age, ethnicity and season (except Winter).&#x0D; Conclusions: The greater prevalence of hypovitaminosis D in the females than the males in the face of high rate in the overall hospital-visiting clearly calls for necessary strategies in the form of further studies and judicious prescription of supplementary vitamin D in the target population.

A mathematical model of the locomotion of bacteria near an inclined solid substrate: effects of different waveforms and rheological properties of couple-stress slime

Morphological mutations in bacterial cell make them the most miscellaneous microscopic group. Their non-flagellated species known as gliding bacteria exhibit self-powered motion and leave an adhesive trail of slime. The self-propelled motion in some gliding bacteria is achieved as a result of backward surface wave in the cell envelope. Motivated by this fact, an undulating surface on a layer of couple-stress fluid is used to model the motion of such gliding bacteria. Five different wave profiles, namely, sawtooth, sinusoidal, triangular, trapezoidal, and square profiles are used to model the waveform of the undulating wave in the outer cell surface. The inclination of the surface is also integrated into the model. The flow equations are set up under the lubrication assumption. Stream function is derived as an elementary function of an organism’s speed, undulation amplitude, and couple-stress parameter with its flow rate. Speed of the glider and flow rate (satisfying equilibrium conditions) are computed by employing modified Newton–Raphson method. These refined values are further utilized to compute the power dissipation. Effects of different waveforms, inclination angle, gravitational and couple-stress parameters on the speed of the microorganism and rate of energy expended are also quantified. Slime velocity is also plotted for fixed glider. In addition, making use of the obtained realistic set of values of the organism’s speed, flow rate, occlusion parameter, and couple-stress parameter, streamline patterns of the slime are plotted and discussed in detail.

Microbial diversity in Huguangyan Maar Lake of China revealed by high–throughput sequencing

Huguangyan Maar Lake is a typical maar lake in the southeast of China. It is well preserved and not disturbed by anthropogenic activities. In this study, microbial community structures in sediment and water samples from Huguangyan Maar Lake were investigated using a high–throughput sequencing method. We found significant differences between the microbial community compositions of the water and the sediment. The sediment samples contained more diverse Bacteria and Archaea than did the water samples. Actinobacteria, Betaproteobacteria, Cyanobacteria, and Deltaproteobacteria predominated in the water samples while Deltaproteobacteria, Anaerolineae, Nitrospira, and Dehalococcoidia were the major bacterial groups in the sediment. As for Archaea, Woesearchaeota (DHVEG–6), unclassified Archaea, and Deep Sea Euryarchaeotic Group were detected at higher abundances in the water, whereas the Miscellaneous Crenarchaeotic Group, Thermoplasmata, and Methanomicrobia were significantly more abundant in the sediment. Interactions between Bacteria and Archaea were common in both the water column and the sediment. The concentrations of major nutrients ( $$\text{NO}_3^-$$ , $$\text{PO}_4^{3-}$$ , $$\text{SiO}_3^{2-}$$ and $$\text{NH}_4^+$$ ) shaped the microbial population structures in the water. At the higher phylogenetic levels including phylum and class, many of the dominant groups were those that were also abundant in other lakes; however, novel microbial populations (unclassified) were often seen at the lower phylogenetic levels. Our study lays a foundation for examining microbial biogeochemical cycling in sequestered lakes or reservoirs.

Are dark septate endophytes bioindicators of climate in mountain ecosystems?

Dark septate endophytes (DSE), often referred as a miscellaneous group of ascomycetous anamorphic fungi, are making their way in root-microbiome research. Reports, on occurrence of these endophytic fungi, are increasingly emerging from various mountain ecosystems showing their dominance with increasing altitude; also causing shift in colonization of arbuscular mycorrhizal fungi (AMF). Can these DSE be seen as root associated bioindicators for climate change, by anticipating and monitoring shifts in the community structure of root mycorrhizae and endophytes?

Aiding the discovery of new treatments for dementia by uncovering unknown benefits of existing medications

IntroductionThere is a significant need for disease-modifying therapies to treat and prevent dementia, including Alzheimer's disease. Availability of real-world observational information and new analytic techniques to analyze large volumes of data can provide a path to aid drug discovery. MethodsUsing a self-controlled study design, we examined the association between 2181 medications and incidence of dementia across four US insurance claims databases. Medications associated with ≥50% reduction in risk of dementia in ≥2 databases were examined. ResultsA total of 117,015,066 individuals were included in the analysis. Seventeen medications met our threshold criteria for a potential protective effect on dementia and fell into five classes: catecholamine modulators, anticonvulsants, antibiotics/antivirals, anticoagulants, and a miscellaneous group. DiscussionThe biological pathways of the medications identified in this analysis may be targets for further research and may aid in discovering novel therapeutic approaches to treat dementia. These data show association not causality.

Study of antibiotic prescription pattern in PICU of a tertiary care hospital

Background: Infectious disease is one of the importance causes of mortality and morbidity in India, therefore pattern of use of antibiotics requires separate study as they differ from adult, Therefore the aim of our study is to observe the antibiotic prescription in the tertiary care hospital.Methods: A prospective observational study was carried out in the children admitted in PICU. The study was started after obtaining the approval from Institutional Ethics Committee. Written informed consent was obtained from a parent or legal guardian of participants.Results: There were 50 patients were enrolled. The maximum antibiotics were prescribed from cephalosporin class (42; 40.38%) which included ceftriaxone, cefixime, cefotaxim, cefpodoxime. The majority of cephalosporins were prescribed in miscellaneous cases followed by respiratory tract infections, gastrointestinal tract, Central nervous tract infections and nil in CVS cases, secondly higher number of antibiotics prescribed was metronidazole and from Aminopenicillin class which includes amoxiclav and ampicillin and another beta lactamase which includes ureidopenicilin and carbepenem. The majority of aminopenicillin were prescribed in miscellaneous group infections followed by respiratory tract infections.Conclusions: From this study, it can conclude that commonly antibiotic were from 3rd generation cephalosporins followed by metronidazole and other β lactamase inhibitor and all of the antibiotics were prescribed as per the national guidelines.

NEUROLOGICAL PROFILE

Objectives: To determine the Neurological profile of patients residing in therural areas of Sindh during their visit to a tertiary care hospital in Nawabshah. Study Design:Retrospective observational study. Setting: Outpatient Department of Neurology at the PeoplesUniversity of Medical &amp; Health Sciences for Women (PUMHSW), Nawabshah. Period: From14.4.2014 to 31.3.2015. Methods: A questionnaire regarding different Neurological disorderswas developed and data about patients presenting in OPD were registered. The data collectedwas tabulated and analyzed using SPSS 19. Results: A total of 861 patients were registered.Out of these 409 (47.5%) were male and 452 (52.5%) were females with male to female ratio of0.9. The age ranged from 06 months to 90 years and the mean age was 31.57± SD 16.7 7. Out of861 patients 477 (55.4%) visited neurology OPD on their own, 314 (36.47%) on the advice of theirfamily and friends and only 70(8.13%) were referrals by the general practitioners. Majority of thepatients 475 (55.17%) were the residents of villages and small towns while 386 (44.83%) wereresiding in the city of Nawabshah. The frequency of major category of neurological disordersincluding Headache, Epilepsies, Stroke, Neuromuscular disorders, Movement disorders,Spinal cord disorders, Dementias, Psychiatric disorders and Miscellaneous group was 33.%,19.%, 7%, 9%, 4%, 1%, 2%, 16% and 9% respectively. Conclusion: Neurological diseases arecommon among patients residing in the rural areas of Sindh. Headaches, epilepsies, stroke,psychiatric, neuromuscular and miscellaneous disorders were frequent presentations. Lack ofadequate referrals by the general physicians needs to be addressed emphatically. This studyprojects the burden of neurological problems in the under served areas.

Clozapine as a first‐ or second‐line treatment in schizophrenia: a systematic review and meta‐analysis

ObjectiveNo consensus exists on whether clozapine should be prescribed in early stages of psychosis. This systematic review and meta‐analysis therefore focus on the use of clozapine as first‐line or second‐line treatment in non‐treatment‐resistant patients.MethodsArticles were eligible if they investigated clozapine compared to another antipsychotic as a first‐ or second‐line treatment in non‐treatment‐resistant schizophrenia spectrum disorders (SCZ) patients and provided data on treatment response. We performed random‐effects meta‐analyses.ResultsFifteen articles were eligible for the systematic review (N = 314 subjects on clozapine and N = 800 on other antipsychotics). Our meta‐analysis comparing clozapine to a miscellaneous group of antipsychotics revealed a significant benefit of clozapine (Hedges’ g = 0.220, P = 0.026, 95% CI = 0.026–0.414), with no evidence of heterogeneity. In addition, a sensitivity analysis revealed a significant benefit of clozapine over risperidone (Hedges’ g = 0.274, P = 0.030, 95% CI = 0.027–0.521).ConclusionThe few eligible trials on this topic suggest that clozapine may be more effective than other antipsychotics when used as first‐ or second‐line treatment. Only large clinical trials may comprehensively probe disease stage‐dependent superiority of clozapine and investigate overall tolerability.

Tzeananiaceae, a new pleosporalean family associated with Ophiocordycepsmacroacicularis fruiting bodies in Taiwan.

The order Pleosporales comprises a miscellaneous group of fungi and is considered to be the largest order of the class Dothideomycetes. The circumscription of Pleosporales has undergone numerous changes in recent years due to the addition of large numbers of families reported from various habitats and with a large amount of morphological variation. Many asexual genera have been reported in Pleosporales and can be either hyphomycetes or coelomycetes. Phoma-like taxa are common and have been shown to be polyphyletic within the order and allied with several sexual genera. During the exploration of biodiversity of pleosporalean fungi in Taiwan, a fungal strain was isolated from mycelium growing on the fruiting body of an Ophiocordyceps species. Fruiting structures that developed on PDA were morphologically similar to Phoma and its relatives in having pycnidial conidiomata with hyaline conidia. The fungus is characterised by holoblastic, cylindrical, aseptate conidiogenous cells and cylindrical, hyaline, aseptate, guttulated, thin-walled conidia. Phylogenetic analysis based on six genes, ITS, LSU, rpb2, SSU, tef1 and tub2, produced a phylogenetic tree with the newly generated sequences grouping in a distinct clade separate from all of the known families. Therefore, a new pleosporalean family Tzeananiaceae is established to accommodate the monotypic genus Tzeanania and the species T.taiwanensis in Pleosporales, Dothideomycetes. The Ophiocordyceps species was identified as O.macroacicularis and this is a new record in Taiwan.

Benthic archaea as potential sources of tetraether membrane lipids in sediments across an oxygen minimum zone

Abstract. Benthic archaea comprise a significant part of the total prokaryotic biomass in marine sediments. Recent genomic surveys suggest they are largely involved in anaerobic processing of organic matter, but the distribution and abundance of these archaeal groups are still largely unknown. Archaeal membrane lipids composed of isoprenoid diethers or tetraethers (glycerol dibiphytanyl glycerol tetraether, GDGT) are often used as archaeal biomarkers. Here, we compare the archaeal diversity and intact polar lipid (IPL) composition in both surface (0–0.5 cm) and subsurface (10–12 cm) sediments recovered within, just below, and well below the oxygen minimum zone (OMZ) of the Arabian Sea. Archaeal 16S rRNA gene amplicon sequencing revealed a predominance of Thaumarchaeota (Marine Group I, MG-I) in oxygenated sediments. Quantification of archaeal 16S rRNA and ammonia monoxygenase (amoA) of Thaumarchaeota genes and their transcripts indicated the presence of an active in situ benthic population, which coincided with a high relative abundance of hexose phosphohexose crenarchaeol, a specific biomarker for living Thaumarchaeota. On the other hand, anoxic surface sediments within the OMZ and all subsurface sediments were dominated by archaea belonging to the Miscellaneous Crenarchaeota Group (MCG), the Thermoplasmatales and archaea of the DPANN (superphylum grouping Micrarchaeota, Diapherotrites, Aenigmarchaeota, Nanohaloarchaeota, Parvarchaeota, Nanoarchaeota, Pacearchaeota and Woesearchaeota). Members of the MCG were diverse, with a dominance of subgroup MCG-12 in anoxic surface sediments. This coincided with a high relative abundance of IPL GDGT-0 with an unknown polar head group. Subsurface anoxic sediments were characterized by higher relative abundance of GDGT-0, -2 and -3 with dihexose IPL types, GDGT-0 with a cyclopentanetetraol molecule and hexose, as well as the presence of specific MCG subgroups, suggesting that these groups could be the biological sources of these archaeal lipids.

Characterization of Bathyarchaeota genomes assembled from metagenomes of biofilms residing in mesophilic and thermophilic biogas reactors

BackgroundPrevious studies on the Miscellaneous Crenarchaeota Group, recently assigned to the novel archaeal phylum Bathyarchaeota, reported on the dominance of these Archaea within the anaerobic carbohydrate cycle performed by the deep marine biosphere. For the first time, members of this phylum were identified also in mesophilic and thermophilic biogas-forming biofilms and characterized in detail.ResultsMetagenome shotgun libraries of biofilm microbiomes were sequenced using the Illumina MiSeq system. Taxonomic classification revealed that between 0.1 and 2% of all classified sequences were assigned to Bathyarchaeota. Individual metagenome assemblies followed by genome binning resulted in the reconstruction of five metagenome-assembled genomes (MAGs) of Bathyarchaeota. MAGs were estimated to be 65–92% complete, ranging in their genome sizes from 1.1 to 2.0 Mb. Phylogenetic classification based on core gene sets confirmed their placement within the phylum Bathyarchaeota clustering as a separate group diverging from most of the recently known Bathyarchaeota clusters. The genetic repertoire of these MAGs indicated an energy metabolism based on carbohydrate and amino acid fermentation featuring the potential for extracellular hydrolysis of cellulose, cellobiose as well as proteins. In addition, corresponding transporter systems were identified. Furthermore, genes encoding enzymes for the utilization of carbon monoxide and/or carbon dioxide via the Wood–Ljungdahl pathway were detected.ConclusionsFor the members of Bathyarchaeota detected in the biofilm microbiomes, a hydrolytic lifestyle is proposed. This is the first study indicating that Bathyarchaeota members contribute presumably to hydrolysis and subsequent fermentation of organic substrates within biotechnological biogas production processes.

Archaea are prominent members of the prokaryotic communities colonizing common forest mushrooms.

In this study, the abundance and composition of prokaryotic communities associated with the inner tissue of fruiting bodies of Suillus bovinus, Boletus pinophilus, Cantharellus cibarius, Agaricus arvensis, Lycoperdon perlatum, and Piptoporus betulinus were analyzed using culture-independent methods. Our findings indicate that archaea and bacteria colonize the internal tissues of all investigated specimens and that archaea are prominent members of the prokaryotic community. The ratio of archaeal 16S rRNA gene copy numbers to those of bacteria was >1 in the fruiting bodies of four out of six fungal species included in the study. The largest proportion of archaeal 16S rRNA gene sequences belonged to thaumarchaeotal classes Terrestrial group, Miscellaneous Crenarchaeotic Group (MCG), and Thermoplasmata. Bacterial communities showed characteristic compositions in each fungal species. Bacterial classes Gammaproteobacteria, Actinobacteria, Bacilli, and Clostridia were prominent among communities in fruiting body tissues. Bacterial populations in each fungal species had different characteristics. The results of this study imply that fruiting body tissues are an important habitat for abundant and diverse populations of archaea and bacteria.

Correlation of fine needle aspiration cytology and histopathology of neck swellings

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Neck swellings are a common clinical finding affecting all age groups. FNAC is a minimally invasive procedure helpful in the diagnosis of various neck swellings. The purpose of this study is to determine the accuracy of FNAC in the diagnosis of neck swellings by comparing it with the histopathology which is taken as the gold standard.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; A prospective study which included 90 patients who attended ENT and surgery departments of Government Medical College, Trivandrum with neck swellings from July 2006-2007. FNAC of the swelling was done and the FNAC results were compared with the histopathology results. The specificity, sensitivity, positive and negative predictive values and accuracy of FNAC were calculated. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Of the 90 patients, thyroid swelling formed the major group followed by lymph node, salivary gland and miscellaneous swellings. Thyroid swellings had a female predominance while the other three groups namely lymph node, salivary gland and miscellaneous groups showed a male preponderance. When the neck swellings namely thyroid, salivary gland, lymph node and miscellaneous group were taken into consideration as a whole, the sensitivity of FNAC for detecting malignancy was 64.3%. The specificity, positive predictive value, negative predictive value and accuracy were 97.4%, 81.8%, 93.7% and 92% respectively.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; FNAC can be rated as a safe, simple, reliable, cost effective and rapid diagnostic tool with high specificity and sensitivity for the initial evaluation of neck swellings.&lt;/p&gt;

O7.6. META-ANALYSIS OF EFFICACY OF COGNITIVE ENHANCERS FOR PATIENTS WITH SCHIZOPHRENIA-SPECTRUM DISORDERS

BackgroundCognitive impairment is a core feature of schizophrenia, which is predictive for functional outcomes and should therefore be one of the main treatment targets. Pharmacological enhancement of cognition has been a main field of research in the last decades, investigating almost all neurotransmitter systems and reporting positive as well as negative findings. The pathophysiology of cognitive dysfunctions in schizophrenia is complex and many different neurotransmitter systems are involved. This quantitative review provides an overview of studies of pharmacological agents targeting neurotransmitter systems relevant for cognitive deficits in schizophrenia.MethodsIn our systematic search we included pharmacological agents targeting glutamatergic, cholinergic, serotonergic, dopaminergic, GABAergic and noradrenergic neurotransmitter systems, and also a miscellaneous group of agents, including modafinil/armodafinil. We evaluated the effects of cognitive enhancers on overall cognitive functioning as well as on seven cognitive domains, including attention/vigilance, processing speed, reasoning, verbal learning and memory, visual learning and memory, working memory, and verbal fluency.ResultsIn total, 93 studies with 5630 patients were suitable for inclusion in the meta-analysis. The mean sample size was 28.73 (SD=27.13, range=4–203), mean age of the participants was 44.15 years (SD=6.36, as reported by 91 study samples), 68.54% of the sample were men (as reported by 87 study samples), and average illness duration was 15.57 years (SD=6.47, as reported by 63 study samples). Combining all cognitive enhancers across different neurotransmitter systems for the effect on overall cognitive functioning resulted in fifty-one study samples, with a total of 3635 patients. Cognitive enhancers showed a small but significant positive effect size of 0.10 over placebo treatment (p=.023; 95%CI=0.01 to 0.18). Overall, cognitive enhancers showed no positive effects as compared to placebo for the separate domains. When analysing each neurotransmitter system separately, agents acting predominantly on the glutamatergic system showed a small but significant effect size on overall cognitive functioning (Hedges’ g=0.19, p=.01), as well as on working memory (Hedges’ g=0.13, p=.04). A sub-analysis of acetylcholinesterase inhibitors (AChEI) within cholinergic system showed a small effect on working memory (Hedges’ g=0.26, p=.03). No other positive effects of cognitive enhancers as compared to placebo were revealed.DiscussionThe current meta-analysis showed very few favorable effects of cognitive enhancers for patients with schizophrenia spectrum disorders. The overall analysis showed small difference between cognitive enhancers and placebo. Most studies were on agents acting on the glutamatergic and the cholinergic system. There is some evidence of positive effects on cognitive functioning for agents acting on glutamatergic system and acetylcholinesterase inhibitors within cholinergic system. There is still a major lack of studies involving agents acting on other systems. Important issues such as dose, treatment duration, including a younger population and subtyping heterogeneous samples should be taken into account for future studies.

Declining trend in valproate use in Finland among females of childbearing age in 2012-2016 - a nationwide registry-based outpatient study.

Documented teratogenic effects of valproate (VPA) prompted restrictions of its use in females of childbearing age in 2014. We investigated possible annual changes in the outpatient use of VPA in Finland during 2008-2016 with a special focus on women. We identified all outpatients with VPA purchases between 2008 and 2016 categorizing users due to epilepsy, bipolar disorder or miscellaneous indications. Temporal trends in the annual prevalence rates of VPA use were estimated using Poisson regression analyses. Between 2012 and 2016, the prevalence of VPA use among women aged 15-44years decreased by 19%, from 50/10000 to 40/10000 (prevalence rate ratio, 0.81; 95% confidence intervals, 0.77-0.91; P< 0.001). The use of VPA due to epilepsy decreased significantly in females aged 15-24 and 25-34years and that due to bipolar disorders decreased significantly in females aged 25-34 and 35-44years. The use of VPA in the miscellaneous indication group decreased by 32% after 2014 in females aged 15-44years and, most strikingly, by 56% among those aged 15-25years. In women with epilepsy, the use of VPA increased among those over the age of 44years. The rates of female VPA users with childbearing potential have decreased in all three major indication groups in Finland during recent years, especially after the European Medicines Agency restrictions were published in 2014. However, it still remains open to question as to whether the practice of VPA use follows current guidelines. A special concern is the relatively high prevalence of off-label use of VPA in fertile-aged females.

Bacterial and Archaeal Community Structure in the Surface Diatom Sediments of Deep Freshwater Lake Baikal (Eastern Siberia)

ABSTRACTDiatom sediment records of large lakes can be used to decipher the history of ancient phytoplankton. The upper layer of the sediment is an important area of remineralization of the sedimenting phytoplankton biomass. It hosts a bacterial community different from those of both the water column and deeper sediment layers. In this work, we analyzed the structure and diversity of the communities of Bacteria and Archaea in the surface sediment core containing valves of diatoms, the major producers in Lake Baikal. Pyrosequencing of the bacterial V3–V4 region of the 16 S ribosomal RNA (rRNA) and archaeal V1–V3 16 S rRNA gene regions yielded 29,168 and 36,997 reads, respectively. In total, we have identified 33 bacterial phyla; uncultured Actinobacteria were the most abundant in the upper layers, while lower sediment was dominated by Firmicutes and Alphaproteobacteria. The composition of the archaeal community changed with depth, but was generally dominated by Crenarchaeota from the classes Marine Group I and Miscellaneous Crenarchaeotic Group, as well as Euryarchaeota from the class Thermoplasmata. These dominant bacterial and archaeal taxa are presumed to participate in the destruction of buried organic matter, which eventually leads to degradation of the diatom valves.