A minority of neurologists is convinced that the disease "dementia praecox" first described by Emil Kraepelin in 1899 is still valid and its annexation by psychoanalysis and later by psychiatry has caused severe damage. The psychoanalytic extremist Eugen Bleuler had successfully annexed all conceivable mental conditions for Freud's couch therapy and had withdrawn them from medical research by his own postulates, which could never be proven. A recent further study now supports Kraepelin's once discarded thesis in a new way. This gives rise to a commentary by physicians on the clinical front.

Background and Purpose: Phosphodiesterases (PDEs) are a family of enzymes, which hydrolyze cAMP and cGMP. PDE10A is expressed mainly in the medium spiny neurons of the striatum that provides an opportunity to modulate the movement control pathways of the basal ganglia: “direct” (D1 receptor-dependent) and “indirect” (D2 receptor-dependent). Thus, inhibition of PDE10A can functionally mimic the action of both D1 receptor agonists and D2 receptor antagonists, although much less attention has been paid to the assessment of D1 receptor agonist-like effects. The purpose of the present study was (1) to confirm the motor stimulatory effects of PDE10A inhibitors and (2) to test whether these effects are subject to the development of tolerance. Experimental Approach: The ability of single or repeated (5 or 10 days) administration of selective PDE10A inhibitors, MP-10 (0,3-5 mg/kg) and RO5545965 (0.1-0.9 mg/kg), to stimulate locomotor activity was assessed in rats after single tetrabenazine challenge (3 mg/kg). The study was pre-registered on PreclinicalTrials.eu. Key Results: PDE-10A inhibition exerted paradoxical motor stimulatory properties in a dose-dependent manner. However, repeated administration of PDE10A inhibitors led to a reduction of their effects. Conclusion and Implications: PDE-10A inhibition produces a paradoxical increase in motor activity in animals with low dopamine tone. After repeated administration of PDE-10A inhibitors, these effects disappeared. The development of tolerance similar to that previously observed for D1-receptor agonists may limit the potential clinical use of the stimulatory effects of PDE10A inhibitors. Further studies aimed at analyzing the molecular mechanisms of this tolerance are warrant

Objective: the exact link between COVID-19 pandemic and different adverse outcomes of pregnancy remains unclear. Plus, large-scale research is lacking. In the present study, we aimed to compare the maternal and fetal health outcomes during the COVID-19 pandemic with the same last year duration in Iran. Design: Two retrospective cohorts (pre-COVID-19 and during COVID-19) were studied. The pre-COVID-19 cohort include pregnant women who had given birth between 1 January 2019 and 31 December 2019. The COVID-19 cohort, who had given birth between 1 January 2020 and 31 December 2020. The characteristics of pregnant women before COVID-19 and during COVID-19 pandemic were compared with Fisher’s exact test. Uni-variate and multivariate log-binomial regression models were used to determine the risk ratios of the impacts of the COVID-19 pandemic on adverse pregnancy outcomes. Results: among 128968 women showed that women who had given birth during the pandemic were more likely to be of young age, lower rates of alcohol consumption and smoking, lower weight gain, and higher rates of using synthetic milk for feeding neonates (P<0.05). Also, the risks of preterm labor were high (cOR 95% CI, 1.13 to 1.31; p<0.01) and the risk of caesarian were low (cOR 95% CI, 0.95 0.92 to 0.98; p<0.01) among pregnant women who gave birth during the COVID-19 pandemic compared with those who gave birth before the pandemic. Conclusions: In summary, we found that during the COVID-19 pandemic there were the higher risks of preterm labor and lower risk of caesarean among pregnant women.

Objectives: Nasopharyngeal (NP) depth prediction is clinically relevant in performing medical procedures, and enhancing technique precision and safety for patients. Nonetheless, clinical predictive variables and normative data in adults remain limited. This study aimed to determine normative data on NP depth and its correlation to external facial measurements. Methods: A multicenter cross-sectional study obtained data from adults presenting to otolaryngology clinics at five sites in Canada, Italy, and Spain. Investigators compared the endoscopically measured depth from sill to nasopharynx along the nasal floor to the facial measurements “curved distance from the alar-facial groove along the face to the tragus” and “distance from the tragus to a plane perpendicular to the philtrum.” When sinus CT images were available, the distance from the nasopharynx to nasal sill was also collected. Results: 371 patients participated in the study (41% women; 51 years old, SD 18). The average endoscopic depth was 9.4 cm (SD 0.86) and 10.1 cm (SD 0.9) for women and men, respectively (p<0.001; 95% CI 0.46 to 0.86). Perpendicular distance was strongly correlated to NP depth (r=0.775; p<0.001), with an average underestimation of 0.1 cm (SD 0.65; 95% CI 0.06 to 0.2). The equation: ND(cm) = perpendicular distance*0.773 + 2.344, generated from 271 randomly selected participants, and validated on 100 participants, resulted in a 0.03 cm prediction error (SD 0.61; 95% CI -0.08 to 0.16). Conclusions: Nasopharyngeal depth can be accurately approximated by the distance from the tragus to a plane perpendicular to philtrum. The generated predictive equation was most accurate but not likely clinically relevant.

In the early 2010s, scientists realized that CRISPR/Cas9, a bacterial immune defense system against viruses that involves the CRISPR-associated protein #9 (Cas9) endonuclease enzyme, single-guide RNAs (sgRNAs), and PAM recognition, could be used to intentionally manipulate genes, essentially changing gene expression and regulation in such a way that would allow for a customized genome. Since then, CRISPR technology has revolutionized medical research and the biotechnology industry, and its newfound capabilities have scientists asking if CRISPR can be used to modify genes in such a way that would cure or treat certain harmful or life-threatening diseases. There have been CRISPR-based clinical studies done to treat β-thalassemia (TDT), sickle-cell disease (SCD), the human immunodeficiency virus (HIV), and several other genetic and non-hereditary diseases, but there is still a long way to go before CRISPR can become a widespread treatment for many more such diseases (Ebina et al., 2013; Esrick et al., 2021; Frangoul et al., 2021). Currently, researchers are looking to see if CRISPR is an accurate, specific, non-harmful, and effective treatment for these diseases, which means addressing and eliminating potential concerns about its safety and efficacy through extensive pre-clinical and clinical research, as well as overcoming moral and social obstacles. In this review, I will look at how the CRISPR/Cas9 gene-editing system can be applied in humans to prevent, cure, or treat these diseases, as well as what needs to be done before the CRISPR/Cas9 system can be made publicly available as a medical treatment for diseases.

• Non-functional larynx (NFL) was found to affect 30.9 % of patients with locally advanced laryngeal cancer who underwent curative non-surgical laryngeal preservation treatment for stage III/IV disease • The key measures of NFL were long-term gastrostomy and tracheostomy dependence, functional laryngectomy and chronic aspiration. • Multivariate analyses identified current smoking to be associated with 6.8-fold increase in NFL • Patients with pre-treatment hemi-laryngeal fixation were 3.4 times more likely to experience locoregional recurrence.

Ecological knowledge is produced through hypothetico-deductive methods fueled by natural history observations. Nevertheless, the biologist-naturalist is becoming a rare species. The lack of incentive and financial investment to natural history related courses, as taxonomy, field biology, and organismal biology is constantly diminishing the graduation of ecologists with first-hand knowledge about nature. The interdependence between natural history and ecology science demands more student training in natural history while updating college curricula and teaching strategies to increase the number of graduates with significant field experiences.

The Ponto-Caspian Bloody-red mysid shrimp (Hemimysis anomala) was discovered in a large freshwater reservoir in the south-east of England in 2020 (Abberton reservoir, Essex, UK). The shrimp was discovered while carrying out aquatic invertebrate surveys across a range of permanent, semi-permanent and seasonal habitats between October and December 2020. The shrimp were found in semi-permanent lagoons adjacent to and connected to the main reservoir and in shallow water bays in the main reservoir. Surveys conducted in January 2021 along a reservoir wall also found the shrimp but no accurate abundance estimates were made. Surveys conducted across the same sites with increased effort in July 2021 did not find any individuals in lagoons, bays or off the reservoir wall in either shallow or deep shelves. The identity of the species was confirmed with high magnification inverted light microscopy due to the shape and setae distribution of the antennal scale and telson in addition to the characteristic bloody red colour of the shrimp pre-preservation. Previous introductions of this species to the UK have been identified before, but whether these propagules arrived from natural or anthropogenic introductions was not clear. Abberton reservoir has no public access for boating or recreational activities other than a small, restricted local angling group but is an internationally important site for migratory and overwintering waterfowl and waders. The migration routes of several waterfowl species for which Abberton is noted would mean that this new shrimp species is likely to have been introduced from either its native range or from its expanded non-native range in the UK or Netherlands by birds. It is not yet confirmed that this discovery represents a successful invasion of this species at Abberton and if it is, when it arrived or what effects it may be having on the food web of this site.

We report here a case of IMOS of the tibia shafts, diagnosed in a 53-year-old man. Medical history did not reveal a history of trauma or infection or familial bone disease and all other causes of osteosclerosis were excluded. The X-Rays showed extensive sclerotic intramedullary lesion of the tibia shafts

Severe Acute Respiratory Coronavirus Syndrome 2 (SARS-CoV-2) is a new human coronavirus family discovered during the highly communicable respiratory disease outbreak in Wuhan, China, in 2019. Various COVID-19 vaccines are up to 95% effective against symptomatic infections caused by the COVID-19. Whether people with PD or PS have an increased risk of COVID-19 and are associated with a higher risk of death is still uncertain. In this study, we report eleven cases of PD patients who died whitin 24 hours after vaccination with the Sinopharm. All patients were over 79 years old (84.64 ± 5.08). All patients were SARS-CoV2 PCR negative and took their first dose of the Sinopharm. All patients had a duration of more than 5 years with PD. All patients presented to the hospital less than 12 hours after vaccination. All patients died less than 24 hours after vaccination. In this study, All the patients were elderly and hypertension and diabetes were seen in 11 (100%) and 7 (63.6%) patients which could reinforce the hypothesis that older patients with PD should be vaccinated more cautiously and these patients should be discussed the vaccine with their physician especially in patients who have other comorbidities. Because our report was a case series study, we only identified patients, and the causality could not be assumed or proven.

How populations diverge into different lineages is a central issue in evolutionary biology. Despite the increasing evidence indicating that such divergences do not need geographic isolation, numerous phenotypic differentiations show a distributional correspondence. In addition, gene flow has been widely detected during and through such diverging processes. We used one widely distributed Aquilegia viridiflora complex as a model system to examine genomic differentiation and corresponding phenotypic variations along geographic gradients. Our phenotypic analyses of 90 individuals from 20 populations from northwest to northeast China identified two phenotypic groups along the geographic cline. All examined traits are distinct between them although a few intermediate individuals occur in their contacting regions. We further sequenced the genomes of the representative individuals of each population. However, we recovered four distinct genetic lineages based on both nuclear genomes and plastomes that were different from phenotypic differentiation. In particular, we recovered numerous genetic hybrids in the contact regions of four lineages. Gene flow is widespread and continuous between four lineages but much higher between contacting lineages than geographically isolated lineages. In addition, many genes with fast lineage-specific mutations were identified to be involved in local adaptation. Our results suggest that both geographic isolation and local selection exerted by the environment may together create geographic distributions of phenotypic variations as well as the underlying genomic divergences in numerous lineages.

Using the multipoles method, we formulate the problems of diffraction (both surge and heave) of water waves by a submerged prolate spheroidal body in deep water with an ice-cover, with the ice-cover being modelled as an elastic plate of very small thickness. It investigates the linear hydrodynamic diffraction problem by prolate spheroidal body and obtained the analytical solution for the associated boundary value problem. The structural model is a spheroidal with its polar axis greater than its equatorial diameter, subjected to the action of incident wave. The hydrodynamic forces (Surge and heave exciting forces) are obtained and depicted graphically against the wave number for various parameters and also the flexural rigidity of the ice-cover to show the effect of the presence of ice-cover on these quantities. When the flexural rigidity is taken to be zero, the numerical results for the forces for water with free surface are recovered.

Accumulating evidence for trade-offs involving metabolic traits has demonstrated their importance in evolution of organisms. Metabolic models with different level of complexity have already been considered when investigating mechanisms that explain various metabolic trade-offs. Here we provide a systematic review of modelling approaches that have been used to study and explain trade-offs between: (i) kinetic properties of individual enzymes, (ii) rates of metabolic reactions, (iii) rate and yield of metabolic pathways and networks, (iv) different metabolic objectives in single organisms and in metabolic communities, and (v) metabolic concentrations. In providing insights into mechanisms underlying these five types of metabolic trade-offs obtained from constraint-based metabolic modelling, we emphasize the relation of metabolic trade-offs to the classical black box Y-model that provides conceptual explanation for resource acquisition-allocation trade-offs. In addition, we identify several pressing concerns and offer a perspective for future research in the identification and manipulation of metabolic trade-offs by relying on the toolbox provided by constraint-based metabolic modelling for single organisms and microbial communities.

Trade-offs between traits arise and reflect constraints imposed by the environment and physicochemical laws. Trade-off situations are expected to be highly relevant for sessile plants, which have to respond to changes in the environment to ensure survival. Despite increasing interest in determining the genetic and molecular basis of plant trade-offs, there are still gaps and differences with respect to how trade-offs are defined, how they are measured, and how their genetic architecture is dissected. The first step to fill these gaps is to establish what is meant by trade-offs. In this review we provide a classification of the existing definitions of trade-offs according to: (1) the measures used for their quantification, (2) the dependence of trade-offs on environment, and (3) whether data based on which they are inferred are from a single individual across different environments or a population of individuals in single or multiple environments. We then compare the approaches for quantification of trade-offs based on phenotypic, between-individual, and genetic correlations, and stress the need for developing further quantification indices particularly for trade-offs between multiple traits. Lastly, we highlight the genetic mechanisms underpinning trade-offs and experimental designs that facilitate their discovery in plants, with focus on usage of natural variability. This review also offers a perspective for future research aimed at identification of plant trade-offs, dissection of their genetic architecture, and development of strategies to overcome trade-offs, with applications in crop breeding.

An 18-year-old man presented with the complaints of occasional headache and limb weakness associated with slurring of speech and purposeless laughing. Magnetic resonance imaging showed a diffuse altered signal intensity area involving the pons with asymmetrical expansion. The patient underwent surgical resection. Histology revealed WHO grade IV glioblastoma.

Graph theory has many applications in the chemistry and analysis of molecular structures and has grown popular. Topological descriptors are numeric numbers that contain chemical information and provide structural features of compounds relevant to the chemical approach. The most important components in topological indices are the physical-chemical properties of essential chemical substances. The molecular graph of 2D silicon-carbide structures is investigated in this paper. The scope of this paper is to determine the bond-breaking energy and the stability measure of silicon-carbides with topological indices.

A 63-year-old male patient of diabetic ketoacidosis and septic shock was started on norepinephrine infusion following which he developed bulla and subcutaneous tissue ischemia in the event of inadvertent extravasations of norepinephrine. The patient improved after management with mechanical debridement of necrosed tissue and regular dressing of the wound.

The Sombor indices, a new category of degree-based topological molecular descriptors, havebeen widely investigated due to their excellent chemical applicability. This paper aims to establishSombor indices distributions in random polygonal chain networks and to achieve expressions of theexpected values and variances. The expected values and variances of the Sombor indices for polyonino,pentachain, polyphenyl, and cyclooctane chains are obtained. Since the end connection of a randomchain network follows a binomial distribution, the Sombor indices of any chain network follow the normaldistribution when the number of polygons connected by the chain, indicated by n, approaches infinity.

In computational chemistry, numbers programming certain structural skin appearance of natural molecules and derivative from the parallel molecular graph are called the graph invariants or more frequently topological indices. Topological indices are numeric quantity that are derived from a molecular graph by mathematical calculations. In QSAR and QSPR study, topological indices are utilized to guess the bioactivity of chemical compounds. The Symmetric Division deg (SDD) is good estimate of total surface area for polychlorobiphenlys. In this paper we process the Symmetric Division deg index for Silicate, Oxide and Copper(II) Oxide network. We compare above network of Symmetric division deg index based on degree and neighbhourhood.

The multiple signal classification (MUSIC) method for direction-of-arrival (DOA) estimation is widely applied in practical scenarios. However, the MUSIC method with planar array requires two-dimensional (2D) on-grid spectrum searches, which would lead to the grid mismatch and high computational complexity. Therefore, a high precision fast DOA estimation method for planar array is proposed. In the proposed method, a two-stage grid search approach over the 2D spectrum is firstly applied to obtain a quick coarse estimation of DOA. Then the estimation of higher precision is achieved via a quadratic surface fitting method. Simulation results verified the effectiveness of the proposed method.

A document by Sara Zaidi. Click on the document to view its contents.

The CRISPR-Cas system of Prokaryotes is an adaptive immune defense mechanism to protect themselves from invading genetic elements (e.g. phages and plasmids). Studies that describe the genetic organization of these prokaryotic systems have mainly reported on the Enterobacteriaceae family (now reorganized within the order Enterobacteriales). For some genera, data on CRISPR-Cas systems remain poor, as in the case of Serratia (now part of the Yersiniaceae family) where data are limited to a few genomes of the species marcescens. This study describes the detection, in silico, of CRISPR loci in 146 Serratia complete genomes and 336 high-quality assemblies available for the species ficaria, fonticola, grimesii, inhibens, liquefaciens, marcescens, nematodiphila, odorifera, oryzae, plymuthica, proteomaculans, quinivorans, rubidaea, symbiotic, and ureilytica. Apart from subtypes I-E and I-F1, which had previously been identified in marcescens, we report that of I-C and the variants I-ES1, I-ES2 and I-F1S1. Analysis of the genomic contexts for CRISPR loci revealed mdtN-phnP as the region mostly shared (grimesii, inhibens, marcescens, nematodiphila, plymuthica, rubidaea, and Serratia sp.). Three new contexts detected in genomes of rubidaea and fonticola (puu genes-mnmA) and rubidaea (osmE-soxG and ampC-yebZ) were also found. Plasmid and/or phage origin of spacers was also established.

Purpose: Leaders in academic health sciences centres (AHCs) must navigate multiple roles as an inherent component of their positions. Changing accountabilities, varying expectations, differing leadership competencies required of multiple leadership roles can be exacerbated by health system disruption, such as during the COVID-19 pandemic. We need improved models that support leaders in navigating, so they can better handle the complexity of multiple leadership roles.Method: This integrative conceptual review sought to examine leadership and followership constructs and how they intersect with current leadership practices in AHCs. The goal was to develop a refined model of health care leadership development. The authors used iterative cycles of divergent and convergent thinking to explore and synthesize various literature and existing leadership frameworks. The authors used simulated personas and stories to test the model and, finally, the approach sought feedback from knowledge users (including health care leaders, medical educators, and leadership developers) to offer refinements. Results: After five rounds of discussion and reformulation, the authors arrived at a refined model: the LEADS+ Developmental Model. The model describes four nested stages, organizing progressive capabilities, as an individual toggles between followership and leadership. During the consultation stage, feedback from 29 out of 65 recruited knowledge users (44.6% response rate) was acquired. More than a quarter of respondents served as a senior leader in a health care network or national society (27.5%, n=8).  Consulted knowledge users were invited to indicate their endorsement for the refined model using a 10-point scale (10=highest level of endorsement). There was a high level of endorsement: 7.93 (SD 1.7) out of 10. Conclusion: The LEADS+ Developmental Model may help foster development of academic health centre leaders. In addition to clarifying the synergistic dynamic between leadership and followership, this model describes the paradigms adopted by leaders within health systems throughout their development journey.

Background and Purpose: Dysregulation of adult hippocampal neurogenesis is linked to major depressive disorder (MDD), with more than 300 million people diagnosed and worsened by the COVID-19 pandemic. Accumulating evidence for Neuropeptide Y (NPY) and galanin (GAL) interaction was shown in various limbic system regions at molecular-,cellular- and behavioral-specific levels. The purpose of the current work was to evaluate the proliferating role of GALR2 and Y1R agonists interaction upon intranasal infusion in the ventral hippocampus. Experimental approach: We studied their hippocampal proliferating actions using the proliferating cell nuclear antigen (PCNA) and the expression of of the brain-derived neurothrophic factor (BDNF). Moreover, we studied the formation of Y1R-GALR2 heteroreceptor complexes and analyzed morphological changes on hippocampal neuronal cells. Finally, the functional outcome of the NPY and GAL interaction on the ventral hippocampus was evaluated in the forced swimming test. Key Results: We demonstrated that the intranasal infusion of GALR2 and the Y1R agonists promotes cell proliferation in the DG of the ventral hippocampus and the induction of the neurotrophic factor BDNF. These effects were mediated by the increased formation of Y1R-GALR2 heteroreceptor complexes, which may mediate the neurites outgrowth observed on neuronal hippocampal cells. Importantly, BDNF action was found necessary for the antidepressant-like effects after GALR2 and the Y1R agonists intranasal administration. Conclusions & Implications: Our data may suggest the translational development of new heterobivalent agonist pharmacophores acting on Y1R–GALR2 heterocomplexes in the ventral hippocampus for the novel therapy of mayor depression disorder or depressive-affecting diseases.