Background and Purpose: The Covid-19 is a viral infection classified as a pandemic by the World Health Organization. There is not currently therapy against the Sars-cov-2. We aimed to assess the best drug therapy approach for the management of Covid-19. Experimental Approach: We did a systematic review and meta-analysis of randomized controlled trials of drugs used in patients with Covid-19. We performed research in the PubMed and the Medrxiv. The trials were included if the patients were over 12 years old, diagnosed through the rt-PCR test and who assessed as primary outcomes or decreased mortality, or time to clinical improvement, or hospitalization time. Random-effects meta-analysis was used to pool individual studies. Heterogeneity was assessed using I². The review has been registered on PROSPERO, number 179879. Key Results: Nine trials were included for analysis. Remdesivir, mainly early after the onset of symptoms, led to a reduction in mortality (OR, 0·85; 95% CI, 0·05 to 0·98; P=0·045). Although this meta-analysis did not observe a reduction using dexamethasone, the Recovery Trial indicates that it can be an option for a patient that needs oxygen support. Our study did not demonstrate the efficacy of any treatment to minimize the effects of Covid-19 related to large hospital stay or time to clinical improvement. Conclusion and Implications: Remdesivir is the only drug that can change the course of Covid-19, reducing mortality rates. Despite this result, other studies must evaluate the effectiveness of this and other drugs in the management of Covid-19 mainly studies with robust methods.

Rationale, aims & objectives: This evaluation was carried out in order to determine the efficacy of the Norfolk and Waveney Adult ADHD Service. With the service not commissioned to offer non-pharmacological support, and with a gap in the research literature, evidence on whether the service model was effective at reducing the impact of ADHD symptoms on service users was needed in order to justify longer term commissioning. Method: Case notes of 113 individuals going through their medication titration process were observed. Scores from the Weiss Functional Impairment Rating Scale (WFIRS), which was routinely collected in the service pre- and post- titration onto ADHD medication, were recorded for comparison. Results: A T test revealed significant improvements in functioning across all domains of the WFIRS after successful titration onto ADHD medication. However, 19.5% of the sample disengaged from the service prior to completing titration. A further 12.5% of the sample did not complete titration due to various factors discussed. Conclusion: While medication has been shown to be effective at improving impairment of functioning in adults with ADHD, high levels of disengagement suggest that more needs to be offered to this population.

Papillary muscle rupture is one of the rare and potentially life-threatening complication usually following acute myocardial infarction (AMI). Acute papillary muscle rupture (PMR) results in severe mitral regurgitation rapidly progressing to florid pulmonary edema and cardiogenic shock. Without emergent surgical intervention, the mortality is extremely high. The management of STEMI patients in COVID 19 pandemic is difficult and challenging. We present an unusual case of 56 years old male who presented with acute inferior wall myocardial infarction (IWMI), underwent successful thrombolysis, developed reinfarction 5 days later complicated by acute postero-medial papillary muscle rupture (PPMR) leading to severe acute mitral regurgitation.

Plant biomass constitutes the main resource of renewable carbon in the planet and its valorization has traditionally been focused on the use of cellulose, although hemicellulose is the second most abundant group of polysaccharides on earth. Enzymes involved in its degradation are usually glycosyl hydrolases and filamentous fungi are good producers of these enzymes. In this study, a new strain of Aspergillus niger was utilized for hemicellulase production under solid state fermentation using wheat straw as a single carbon source. Physicochemical parameters for production of an endoxylanase were optimized by using one factor at a time approach and response surface methodology (RSM). Maximum xylanase yield after RSM optimization was increased 3-fold. The enzyme was purified by ultrafiltration and ion-exchange chromatography1.41-fold, with 6.2 % yield. Highest xylanase activity was observed at 50 °C and pH 6. A high pH and thermal stability were found, greater than 90% residual activity between pH 3.0-9.0 and between 30-40°C, after 24 h of incubation, presenting half-lives of 30 min at 50 and 60°C. Enzyme was mostly active for wheat arabinoxylan, and displayed the following kinetic parameters Km of 26.06 mg•ml-1 and Vmax of 5,647 U•mg-1min-1.Wheat straw xylan hydrolysis with the purified β-1,4 endoxylanase showed that it was able to release xylooligosaccharides, making it suitable for different applications in food technology.

Habitat structure is a key determinant of variation in biodiversity. The effects of increased vertical and horizontal vegetation structure can result in marked shifts in animal communities. This is particularly true for ants in response to woody thickening, with predicted negative impacts on ant diversity. We used pitfall traps to study the response of epigeic ants in two co-occurring dominant habitats (closed and open) of an African savanna biome experiencing extensive woody thickening. Although species richness was higher in open habitats, evenness was significantly lower. Thickening explained significant amounts of variation in ant composition, but site-specific characteristics and seasonality were more important. These site-specific characteristics were largely linked to Anoplolepis custodiens, a species that were locally abundant in open habitats with clayey soils, where they often accounted for more than 90% of all ant activity. As A. custodiens also responds positively to disturbance, indiscriminate bush clearing could lead to knock on effects associated with the numerical and behavioural dominance of this species.

Objective: To investigate concordance in perceptions of communication among participants in family discussions and assess the importance of different domains of communication in a neurocritical care unit. Methods: Prospective observational study conducted in a neurocritical care unit. Our study involved family discussions regarding plan of care for patients admitted to the unit. All participants completed a survey. The first 4 questions rated understanding of the discussion and general satisfaction; the remaining questions were open-ended to assess quality of communication by the physician leading the discussion. Responses were scored and compared among participants using a Likert scale. A difference of < 1 in scores among participants was rated as concordance, while > 2 was designated as discordance. All open-ended responses were classified into six domains. Results: We observed 35 family discussions. Questions 1-3 yielded 99 cross-comparisons per question (total of 297 compared responses). Most responses were either “Strongly Agree” or “Agree”; with “Neutral” or “Disagree” responses being more prevalent in Question 2. Overall concordance of responses between participants was 88%. Education was the most frequently cited domain of communication in response to open-ended questions. Among family and neutral observers, empathy was frequently listed, while providers more often listed family engagement. Conclusion: Overall, satisfaction was high among providers, families, and the observer regarding quality of communication during family discussions in the unit. Perceptual differences emerged over whether this communication impacted healthcare decision-making during that encounter.

Equine chorionic gonadotropin (eCG) is a heterodimeric glycoprotein hormone produced by pregnant mares that has been used to improve reproduction activity in different types of livestock. Several strategies to produce the hormone in a recombinant way have been reported; nevertheless, none approach has been able to produce a recombinant eCG (reCG) with significant in vivo bioactivity or in sufficient quantities for commercial purposes. For this reason, the only current product available on the market consists of partially purified preparations from serum of pregnant mares (PMSG). Herein, we describe a highly efficient process based on third-generation lentiviral vectors as delivery method for the production of reCG in suspension CHO-K1 cells, with productivities above 20 IU.106 cell-1.d-1 and 70% purification yields after one purification step. Importantly, reCG not only demonstrated biological activity in bovine cattle but also this bioactivity appeared to be higher than PMSG, since 140 IU of reCG were needed to exert the same biologic effect in an ovulation synchronization protocol compared to 400 IU of PMSG. The results obtained show that the developed strategy represents an attractive option to produce reCG and constitutes an auspicious alternative for the replacement of animals as a source of PMSG.

Rapidly expanding thyroid lesions with tracheal invasion are typical characteristics of anaplastic and high-grade thyroid carcinomas. However, primary thyroid lymphoma (PTL) must also be considered as a differential. We present a rare case of PTL with direct invasion and compression of the trachea resulting in pulmonary oedema and cardiomyopathy.

Maturity-onset diabetes of the young (MODY) is a group of monogenic diabetes characterized by an autosomal dominant inheritance. MODY is categorized by a large variety of clinical forms and is caused by a wide spectrum of mutations in MODY‑related genes that lead to different clinical pictures and require distinct treatment

Diagnostic failure has emerged as one of the most significant threats to patient safety, and it is important to understand the antecedents of such failures. A consensus has developed in the literature that the majority are due to individual or system factors or some combination of the two. A major source of variance in individual clinical performance is due to cognitive and affective biases, however, their role in clinical decision making has been difficult to assess partly because they are difficult to investigate experimentally. A significant drawback has been that experimental manipulations appear to confound assessment of the context surrounding the diagnostic process itself. The present qualitative study uses a detailed narrative account of selected actual cases of diagnostic error to explore the effect of biases in the ‘real world’ emergency medicine (EM) context. Thirty anonymized EM cases were analysed in depth through a process of root cause analysis that included an assessment of error producing conditions, knowledge-based errors, and how clinicians were thinking and deciding during each case. A prominent feature of the study was the identification of specific cognitive and affective biases – through a process called cognitive autopsy. The cases covered a broad range of diagnoses across a wide variety of disciplines. A total of 24 discrete cognitive and affective biases that contributed to misdiagnosis were identified and their incidence recorded. 5-6 biases were detected per case, and observed on 168 occasions across the 30 cases. Thirteen error-producing conditions (EPCs) were identified. Knowledge-based errors were rare, occurring in only 5 definite instances. The ordinal position in which biases appeared in the diagnostic process was recorded. This study provides a base-line for understanding the critical role that biases play in clinical decision making and sheds light on important aspects of the diagnostic process.

Steviol glycosides, mostly extracted from Stevia rebaudiana Bertoni, are non-caloric, safe natural sweeteners. Steviosides make up more than 50% of total steviol glycosides but possess a bitter aftertaste, which limits their application as food additives. Trace amounts of rubusosides are acceptable sweeteners, but their supply is limited. In this study, we screened an endophytic bacteria (Lelliottia LST-1) that can specifically convert stevioside into rubusoside and reach a conversion rate of 75.4% after response surface optimization. Potential β-glucosidases GH3-1, GH3-2, GH3-3, and GH3-4 based on whole genome sequencing were expressed and interacted with steviol glycosides to explore principle and process of biological transformation. High-performance liquid chromatography revealed that all enzymes hydrolyzed stevioside and generated rubusoside, but substrate specificity analysis indicated that GH3-2 is the most suitable choice for the durative, steady, and high-efficiency production of rubusoside

A 50-year-old male presented with HIV and an ulcerative mass on the hypopharynx. Initially thought to be malignant, multiple biopsies and surgeries over 19 months did not resolve the lesion. Discovery of the cytopathic effect on biopsy led to diagnosis of HSV pseudotumor. The lesion resolved with valacyclovir treatment.

The interactions of simple and Al, B, N, S, P and Si-doped carbon nanotubes with three sulfur-containing molecules (H2S, SO2 and thiophene) have been investigated to assess their adsorption potencies and sensor abilities. DFT calculations were used to calculate the adsorption energies and NBO parameters. Besides, Population analyses were performed to calculate the energy gaps and reactivity parameters and to obtain DOS plots. The results showed an exothermic interaction of H2S, SO2 and thiophene with simple and doped CNTs while the maximum negative adsorption energies were belonged to Al and B containing complexes. Furthermore, evaluation of second order perturbation energies (obtained from NBO calculations) confirmed that the highest energies were related to B and Al containing intramolecular interactions. The results revealed the favourability of adsorption of SO2 by nanotubes (B and Al doped carbon nanotubes, in particular), in comparing with the other examined adsorbates.

Fed-batch culture currently represents the typical choice for the production of monoclonal antibodies (mAbs) in the biopharmaceutical industry. However, the implementation of perfusion culture process combined with continuous manufacturing has gained attention due to increased productivity and resource savings. In this paper, we compared the host cell protein (HCP) production and profile of mAb1 between fed-batch and perfusion culture processes. Our work demonstrated differences in HCP production based on the type of cell culture process for the first time. We focused on HCPs that get carried through the purification process and are present in the final drug substance at levels impacting antibody quality and stability. Perfusion process had lower HCP levels and enabled higher clearance of problematic HCPs compared to fed-batch suggesting a viable alternative process. Furthermore, our work demonstrates proof of concept of the impact of cell culture process on specific product quality and help to navigate the process design when we move from traditional fed-batch to next-generation perfusion cell culture.

Chinese hamster ovary (CHO) is the most commonly used host cell line for therapeutic protein production. Their exposure to highly concentrated feed solution during fed-batch cultivation can cause an unphysiological osmolality increase (>300 mOsm/kg) affecting cell physiology, morphology, and proteome. In a companion article “Hyperosmolality in CHO Culture: Effects on Cellular Behavior and Morphology” we show that hyperosmolalities of up to 545 mOsm/kg force cells to ablate proliferation and gradually increase their volume, almost triplicating it. CHO cells also exhibit a significant hyperosmolality-dependent mitochondrial activity increase. To get a deeper insight into molecular mechanisms involved in these processes, we performed a comparative quantitative label-free proteome study of hyperosmolality-exposed vs. control CHO cells. Our analysis revealed key differentially expressed proteins mediating mitochondrial activation, oxidative stress amelioration, and cell cycle progression. We also discovered a previously unknown strong regulation of proteins altering cell membrane rigidity and permeability. Among others, we detected three members of septins, filamentous proteins forming diffusion barriers in the cell, to be highly upregulated in response to hyperosmolality. Taken together, our observations correlate well with the recent CHO-based fluxome and transcriptome studies and expose new unknown targets involved in response to hyperosmotic pressure in mammalian cells.

Objective: The choice between neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) remains controversial in the treatment of non-small cell lung cancer (NSCLC). There is no significant difference in NAC and AC’s effectiveness. We investigate the cost-effectiveness of NAC versus AC for NSCLC. Method: A decision tree model was designed from a payer perspective to compare NAC and AC treatments for NSCLC. Parameters included overall survival (OS), surgical complications, chemotherapy adverse event (AE), treatment initiation probability, treatment time frame, treatment cost, and quality of life (QOL). Sensitivity analyses were performed to characterize model uncertainty in the base cases. Result: With the same overall survival, AC treatment strategy produces a cost saving of ￥618.90 and an incremental quality-adjusted life-years (QALY) of 0.10 years per patient. If median OS of NAC is 1.4 months more than AC, NAC would be cost effective (CE) at a ￥35446/QALY threshold. The model was robust enough to handle variations to all input parameters except the overall survival. In the probability sensitivity analysis, AC remained dominant in 54.6% of simulations. Conclusion: The modeled cost effectiveness analysis indicates that with operable NSCLC, AC treatment is more cost effective compared to NAC. If NAC provides a longer survival advantage, this treatment strategy may be cost-effective. The OS is the main factor that influences cost-effectiveness analysis.

1. The Tea Bag Index (Keuskamp et al. 2013) has been developed to allow worldwide comparable data on litter decomposition and has become an important part of several citizen science projects. This commentary shows that it is unsuitable for assessing total decomposition in most environments as it does not account for the role of macrofauna in the decomposition process. 2. Tea bags were placed following the standardised protocol in old growth forest in Borneo (Sabah, East Malaysia). 3. The results shows that more than half of the bags were attacked by termites and they tended to remove the majority of the tea, rendering the Tea Bag Index incalculable. 4. The Tea Bag Index can measure the microbial component of decay, but will significantly underestimate total decay rates in most environments. This method will not give an accurate estimate of decomposition in most biomes.

Introduction and aim of the study: Hospital readmissions represent an increasing and highly expensive cost for National Health Services. Aim of this retrospective case-control study was to compare patients who required one or more repeated hospitalizations to those who had only one, in the year 2018 at the Department of Internal Medicine of Pontedera Hospital (Pisa, Italy). Materials and Methods: All the data were retrieved matching data from our electronic health record with our diagnosis-related group (DRG) software system. Continuous variables were defined means ± standard deviation; categorical variables were given as percentage. The independent sample t test was used for the continuous variables and chi-square test for categorical variables. Significance was inferred for p < 0.05. Results: In 2018 a total of 3012 patients were hospitalized. Among these, 14.1% (n=426; mean age 79.7±11,9; range 23-100) were defined as revolving: data were compared with controls (n=420; 13.9%; mean age 75.9±14.7; range 22-99) who had only one hospitalization. Patients main provenance was in both groups a Home-based health care. Revolving patients showed higher mean age, higher rate of chronic comorbidities and mortality. Cancer was equally distributed in both groups. Sepsis was the most relevant factor associated with re-hospitalizations and mortality. Skin ulcers were present in about half of revolving patients, but they were coded as DRG only in an absolute minority. Conclusions: readmissions to Internal Medicine Departments are frequent and mainly related to the severity of chronic diseases affecting the patients. Sepsis was the most relevant condition associated with readmissions, leading to a very high mortality rate. Skin ulcers affected about half of revolving patients, but their DRG were significantly underestimated. Preventing sepsis and investing resources in chronic diseases assistance, represent a key challenge for the future, especially in an outpatient setting.