Respiratory viral infections are major cause of highly mortal pandemics. They are impacting socioeconomic development and healthcare system globally. These emerging deadly respiratory viruses develop newer survival strategies to live inside host cells and tricking the immune system of host. Currently, medical facilities, therapies and research Cdevelopment teams of every country kneel down before novel corona virus (SARS-CoV-2) which claimed ~2,828,629 lives till date. Thus, there is urgent requirement of novel treatment strategies to combat against these emerging respiratory viral infections. Nanocarriers come under the umbrella of nanotechnology and offer numerous benefits compared to traditional dosage forms. Further, unique physicochemical properties (size, shape and surface charge) of nanocarriers provide additional advantage for targeted delivery. This review discusses in detail about the respiratory viruses, their transmission mode and cell invasion pathways, survival strategies, available therapies, and nanocarriers for the delivery of therapeutics. Further, the role of nanocarriers in the development of treatment therapy against SARS-CoV-2 is also overviewed.

Background: Since the COVID-19 pandemic began in early 2020, there have been many reports that it has had a significant impact on screening, case identification and referral in cancer diagnosis. We investigated the diagnostic and therapeutic status of breast malignancy before and after the COVID-19 pandemic at the multi-institution level. Methods: We have reviewed the records of patients with breast cancer from February 2019 to July 2020 in six university hospitals in Korea. The patients were divided into two groups according to the initial date of cancer diagnosis: Period A, from February to April and Period B, from May to July in 2020. The two groups were compared for the same periods in 2019. The goals were to determine whether breast cancer screening and diagnosis have been delayed and thus resulted in stage migration. We also examined the difference in the number of surgeries in patients diagnosed with breast cancer during those periods. Results: The total of 1,669 breast malignancy diagnosis was made in the grouped periods of 2019, and 1,369 diagnoses in 2020. All patients were screened by PCR test for COVID-19 prior to hospitalization, and none of them tested positive. Overall, there was a 9.9% reduction in the number of diagnoses than in 2019 and the decrease was more significant in Period A (11.1% vs. 8.7%). According to the age, there was no difference until the 30s but decreased from those in their 40s and above. The decline was more pronounced in the elderly. The COVID-19 pandemic has affected breast cancer screening (decreased by 27.4%) and more diminished in Period A (41.0% vs. 19.0%). Invasive breast cancer stage was not statistically different in Period A compare with 2019 (p = 0.170). But the stage in Period B was different (p = 0.032), and more patients were observed in advanced stages in 2020. The decrease in surgery was noticeably observed in Period A (4.6%, from 480 to 438 surgeries) and not in Period B. The analysis of reconstruction surgery was similar. Conclusions: Patients with COVID-19 increased exponentially from late February in Korea. However, the number of patients per day decreased to less than 100 on March 15 and then flattened. The health care system for cancer was not overloaded and restrictions on visiting hospital were minimal. Analysis in the pandemic period of the 6-month showed that the number of breast cancer screening, diagnosis and surgeries decreased compared with the previous year. Those decreases were prominent in Period A when the COVID-19 patient surged. The upstage migration of breast cancer was generally insignificant but slightly occurred in Period B. The outbreak of infectious disease makes patients reluctant to come to the hospital, especially in the elderly. We need to discuss the potential long-lasting deleterious effect of the COVID-19 pandemic on cancer diagnosis and management. And we should prepare for how to deal with the backlog caused by the COVID-19 pandemic.

BACKGROUND: Work-related stress, anxiety and depression (WRSAD) are common, overlapping mental health problems burdened with major medical, occupational, institutional and societal implications. Current occupational health (OH) management of WRSAD is based on clinical and managerial guidelines and individual risk assessment. AIMS: The study sought to identify patterns of OH advice in WRSAD and the relationships between the OH advice, available evidence, experience and expertise of the OH doctors (OHDs). METHODS: A retrospective cross-sectional analysis of 101 first-time OH consultations for WRSAD by nine OHDs. RESULTS: The three most common OH interventions included follow-up OH consultations, adjusted duties and referrals for counselling. All OHDs preferred a light-touch approach but the less experienced and qualified OHDs were more proactive and prescriptive. CONCLUSIONS: In the absence of a specific occupational medical guideline for the management of WRSAD, the OH interventions may be guided by clinical guidelines, individual risk assessment, the clients circumstances or the experience, expertise and preferences of the OHDs. In the study group, OH interventions were under-utilized and not consistently applied. Our findings support the argument for OH guideline for WRSAD to improve the consistency and effectiveness of OH interventions. This is important given the scale of the problem and the recent increase in WRSAD during the COVID-19 pandemic.

Most patients with Covid-19 don't require hospitalization. Here's how one health system tracked their illness, offered support, and identified cases where worsening symptoms required emergency department care or hospitalization.

We propose a novel blocked version of the continuous-time bouncy particle sampler of [Bouchard-C\^ot\'e et al., 2018] which is applicable to any differentiable probability density. This alternative implementation is motivated by blocked Gibbs sampling for state space models [Singh et al., 2017] and leads to significant improvement in terms of effective sample size per second, and furthermore, allows for significant parallelization of the resulting algorithm. The new algorithms are particularly efficient for latent state inference in high-dimensional state space models, where blocking in both space and time is necessary to avoid degeneracy of MCMC. The efficiency of our blocked bouncy particle sampler, in comparison with both the standard implementation of the bouncy particle sampler and the particle Gibbs algorithm of Andrieu et al. [2010], is illustrated numerically for both simulated data and a challenging real-world financial dataset.

The present trial was carried out at the Seo de Sericicultura, Campinas, during the summer of 1970, viewing a comparison between the traditional grass frame used in silkworm rearings since 1940, and the new plastic one, both made in the same cylindrical shape. There were studied 8 treatments x 4 replications with parcels of a thousand silkworrn each. At the end of the experiment, it was concluded that the worms preferred the plastic frames, and it was observed that they were able to climb them quicker than the grass-made ones.

SARS-CoV-2 spike protein with D614G substitution has become the dominant variant in the ongoing COVID-19 pandemic. Several studies to characterize the new virus expressing G614 variant show that it exhibits increased infectivity compared to the ancestral virus having D614 spike protein. Here, using in-silico mutagenesis and energy calculations, we analyzed inter-residue interaction energies and thermodynamic stability of the dominant (G614) and the ancestral (D614) variants of spike protein trimer in closed and partially open conformations. We find that the local interactions mediated by aspartate at the 614th position are energetically frustrated and create unfavourable environment. Whereas, glycine at the same position confers energetically favourable environment and strengthens intra-as well as inter-protomer association. Such changes in the local interaction energies enhance the thermodynamic stability of the spike protein trimer as free energy difference (G) upon glycine substitution is ?2.6 kcal/mol for closed conformation and ?2.0 kcal/mol for open conformation. Our results on the structural and energetic basis of enhanced stability hint that G614 may confer increased availability of functional form of spike protein trimer and consequent in higher infectivity than the D614 variant.

BACKGROUND: Altered coagulation and alveolar injury are the hallmarks of acute respiratory distress syndrome (ARDS). However, whether the biomarkers that reflect pathophysiology differ depending on the etiology of ARDS has not been examined. This study aimed to investigate the biomarker profiles of coagulopathy and alveolar epithelial injury in two subtypes of ARDS: patients with direct common risk factors (dARDS) and those with idiopathic or immune-related diseases (iARDS), which are classified as ARDS without common risk factors based on the Berlin definition. METHODS: This retrospective, observational study included adult patients who were admitted to the intensive care unit (ICU) at a university hospital with a diagnosis of ARDS with no indirect risk factors. Plasma biomarkers (thrombinCantithrombin complex [TAT], plasminogen activator inhibitor [PAI]-1, protein C [PC] activity, procalcitonin [PCT], surfactant protein [SP]-D, and KL-6) were routinely measured during the first 5 days of the patients ICU stay. RESULTS: Among 138 eligible patients with ARDS, 51 were excluded based on the exclusion criteria (n = 41) or other causes of ARDS (n = 10). Of the remaining 87 patients, 56 were identified as having dARDS and 31 as having iARDS. Among the iARDS patients, TAT (marker of thrombin generation) and PAI-1 (marker of inhibited fibrinolysis) were increased, and PC activity was above normal. In contrast, PC activity was significantly decreased, and TAT or PAI-1 was present at much higher levels in dARDS compared with iARDS patients. Significant differences were also observed in PCT, SP-D, and KL-6 between patients with dARDS and iARDS. The receiver operating characteristic (ROC) analysis showed that areas under the ROC curve for PC activity, PAI-1, PCT, SP-D, and KL-6 were similarly high for distinguishing between dARDS and iARDS (PC 0.86, P = 0.33; PAI-1 0.89, P = 0.95; PCT 0.89, P = 0.66; and SP-D 0.88, P = 0.16 vs. KL-6 0.90, respectively). CONCLUSIONS: Coagulopathy and alveolar epithelial injury were observed in both patients with dARDS and with iARDS. However, their biomarker profiles were significantly different between the two groups. The different patterns of PAI-1, PC activity, SP-D, and KL-6 may help in differentiating between these ARDS subtypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-019-2559-6) contains supplementary material, which is available to authorized users.

BACKGROUND: Voice features have been suggested as objective markers of bipolar disorder (BD). AIMS: To investigate whether voice features from naturalistic phone calls could discriminate between (1) BD, unaffected first-degree relatives (UR) and healthy control individuals (HC); (2) affective states within BD. METHODS: Voice features were collected daily during naturalistic phone calls for up to 972 days. A total of 121 patients with BD, 21 UR and 38 HC were included. A total of 107.033 voice data entries were collected [BD (n = 78.733), UR (n = 8004), and HC (n = 20.296)]. Daily, patients evaluated symptoms using a smartphone-based system. Affective states were defined according to these evaluations. Data were analyzed using random forest machine learning algorithms. RESULTS: Compared to HC, BD was classified with a sensitivity of 0.79 (SD 0.11)/AUC = 0.76 (SD 0.11) and UR with a sensitivity of 0.53 (SD 0.21)/AUC of 0.72 (SD 0.12). Within BD, compared to euthymia, mania was classified with a specificity of 0.75 (SD 0.16)/AUC = 0.66 (SD 0.11). Compared to euthymia, depression was classified with a specificity of 0.70 (SD 0.16)/AUC = 0.66 (SD 0.12). In all models the user dependent models outperformed the user independent models. Models combining increased mood, increased activity and insomnia compared to periods without performed best with a specificity of 0.78 (SD 0.16)/AUC = 0.67 (SD 0.11). CONCLUSIONS: Voice features from naturalistic phone calls may represent a supplementary objective marker discriminating BD from HC and a state marker within BD.

BACKGROUND. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. METHODS. To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. FINDINGS. The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. INTERPRETATION. Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

The COVID-19 pandemic has spread worldwide, with considerable public health and socio-economic impacts that are seriously affecting health and safety of workers, as well as their employment stability. Italy was the first of many other western countries to implement extended containment measures. Health workers and others employed in essential sectors have continued their activity, reporting high infection rate with many fatalities. The epidemiological trend highlighted the importance of work as a substantial factor to consider both when implementing strategies aimed at containing the pandemic and shaping the lockdown mitigation strategy required for sustained economic recovery. To support the decision-making process, we have developed a strategy to predict the risk of infection by SARS-CoV-2 in the workplace based on the analysis of the working process and proximity between employees; risk of infection connected to the type of activity; involvement of third parties in the working processes and risk of social aggregation. We applied this approach to outline a risk index for each economic activity sector, with different levels of detail, also considering the impact on mobility of the working population. This method was implemented into the national epidemiological surveillance model in order to estimate the impact of re-activation of specific activities on the reproduction number. It has also been adopted by the national scientific committee set up by the Italian Government for action-oriented policy advice on the COVID-19 emergency in the post lockdown phase. This approach may play a key role for public health if associated with measures for risk mitigation in enterprises through strategies of business process re-engineering. Furthermore, it will make a contribution to reconsidering the organization of work, including also innovation and fostering the integration with the national occupational safety and health (OSH) system.

MAIN CONCLUSION: This review analyses the most recent scientific research conducted for the purpose of enhancing artemisinin production. It may help to devise better artemisinin enhancement strategies, so that its production becomes cost effective and becomes available to masses. ABSTRACT: Malaria is a major threat to world population, particularly in South-East Asia and Africa, due to dearth of effective anti-malarial compounds, emergence of quinine resistant malarial strains, and lack of advanced healthcare facilities. Artemisinin, a sesquiterpene lactone obtained from Artemisia annua L., is the most potent drug against malaria and used in the formulation of artemisinin combination therapies (ACTs). Artemisinin is also effective against various types of cancers, many other microbes including viruses, parasites and bacteria. However, this specialty metabolite and its derivatives generally occur in low amounts in the source plant leading to its production scarcity. Considering the importance of this drug, researchers have been working worldwide to develop novel strategies to augment its production both in vivo and in vitro. Due to complex chemical structure, its chemical synthesis is quite expensive, so researchers need to devise synthetic protocols that are economically viable and also work on increasing the in-planta production of artemisinin by using various strategies like use of phytohormones, stress signals, bioinoculants, breeding and transgenic approaches. The focus of this review is to discuss these artemisinin enhancement strategies, understand mechanisms modulating its biosynthesis, and evaluate if roots play any role in artemisinin production. Furthermore, we also have a critical analysis of various assays used for artemisinin measurement. This may help to develop better artemisinin enhancement strategies which lead to decreased price of ACTs and increased profit to farmers.

The topic of digital inclusion and web accessibility for People with Cognitive Disabilities has increased over the COVID-19 pandemic times. The LIVE IT project is attempting to shed some light into this. This piece of work uses insights gained from focus groups and interviews that were held to assess the needs analysis and the existing knowledge gap of this societal problem. To this end, preliminary results of user engagement with digital tools and web services as well as their evaluation are presented herein.

Psychologists worldwide are becoming increasingly concerned about the negative impact of the novel coronavirus (COVID-19) pandemic on adolescents mental health. However, compared to studies involving adults, research using a young population is limited. To further understand the mental health of older adolescents and young adults during the pandemic, the present study examined whether resilience, as a protective factor, buffers the relationship between the personality trait of environmental sensitivity and COVID-19-related distress. In total, 441 older adolescents and young adults (53.7% women, Mage = 18.91 years, SDage = 0.82 years) living in urban Japan completed an online cross-sectional survey in October 2020. The results showed that sensitivity was positively, though weakly, correlated with COVID-19 stress and negatively correlated with resilience. Resilience was negatively correlated with COVID-19 stress. Mediation analysis showed that resilience buffered the negative relationship between sensitivity and COVID-19 stress, and its indirect effect was statistically significant, albeit close to zero. These results suggest that higher sensitivity is not necessarily a vulnerability factor, if resilience can be enhanced.

The purpose of this study was to determine the rate of failure of noninvasive ventilation (NIV) after cardiac surgery in pediatric patients with respiratory failure after extubation and to identify predictive success factors. This was a prospective cohort study of pediatric patients diagnosed with congenital heart disease who underwent heart surgery and used NIV. Data were collected from 170 patients with a median age of 2 months. No patient presented cardiorespiratory arrest nor any other complication during the use of NIV. The success rate for the use of NIV was 61.8%. Subjects were divided for analysis into successful and failed NIV groups. Statistical analysis used Chi-square, MannCWhitney, and Students t tests, which were performed after univariate and multivariate logistic regression for p < 0.05. In the multivariate analysis, only the minimal pressure gradient (OR 1.45 with p = 0.007), maximum oxygen saturation (OR 0.88 with p = 0.011), and maximum fraction of inspired oxygen (FiO(2)) (OR 1.16 with p < 0.001) influenced NIV failure. The following variables did not present a statistical difference: extracorporeal circulation time (p = 0.669), pulmonary hypertension (p = 0.254), genetic syndrome (p = 0.342), RACHS-1 score (p = 0.097), age (p = 0.098), invasive mechanical ventilation duration (p = 0.186), and NIV duration (p = 0.804). In conclusion, NIV can be successfully used in children who, after cardiac surgery, develop respiratory failure in the 48 h following extubation. Although the use of higher pressure gradients and higher FiO(2) are associated with a greater failure rate for NIV use, it was found to be generally safe.

COVID-19 has fundamentally changed how society delivers health care, provides services, and cares for and educates our children. Entrenched problems that seem insurmountable are laid bare for all to see as we weather the pandemic. We cannot afford to tinker around the edges anymore. We must be creative, innovative, and bold to address systemic issues that impact our most under-resourced communities.

EpsteinCBarr Virus (EBV) and Kaposis sarcoma associated-herpesvirus (KSHV) are -herpesviruses that belong to the Herpesviridae family. EBV infections are linked to the onset and progression of several diseases, such as Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC), and lymphoproliferative malignancies arising in post-transplanted patients (PTDLs). KSHV, an etiologic agent of Kaposis sarcoma (KS), displays primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). Many therapeutics, such as bortezomib, CHOP cocktail medications, and natural compounds (e.g., quercetin or curcumin), are administrated to patients affected by -herpesvirus infections. These drugs induce apoptosis and autophagy, inhibiting the proliferative and cell cycle progression in these malignancies. In the last decade, many studies conducted by scientists and clinicians have indicated that nanotechnology and nanomedicine could improve the outcome of several treatments in -herpesvirus-associated diseases. Some drugs are entrapped in nanoparticles (NPs) expressed on the surface area of polyethylene glycol (PEG). These NPs move to specific tissues and exert their properties, releasing therapeutics in the cell target. To treat EBV- and KSHV-associated diseases, many studies have been performed in vivo and in vitro using virus-like particles (VPLs) engineered to maximize antigen and epitope presentations during immune response. NPs are designed to improve therapeutic delivery, avoiding dissolving the drugs in toxic solvents. They reduce the dose-limiting toxicity and reach specific tissue areas. Several attempts are ongoing to synthesize and produce EBV vaccines using nanosystems.

BACKGROUND AND OBJECTIVES Single-site laparoscopic colorectal surgery has been firmly established; however, few reports addressing this technique in the inflammatory bowel disease population exist. METHODS We conducted a case-matched retrospective review of 20 patients who underwent single-site laparoscopic procedures for inflammatory bowel disease compared with 20 matched patients undergoing multiport laparoscopic procedures. Data regarding these patients were tabulated in the following categories: demographic characteristics, operative parameters, and perioperative outcomes. RESULTS A wide range of cases were completed: 9 ileocolic resections, 7 cases of proctocolectomy with end ileostomy or ileal pouch anal anastomosis, 2 cases of proctectomy with ileal pouch anal anastomosis, and 2 total abdominal colectomies with end ileostomy were all matched to equivalent multiport laparoscopic cases. No single-incision cases were converted to multiport laparoscopy, and 2 single-incision cases (10%) were converted to an open approach. For single-incision cases, the mean length of stay was 7.7 days, the mean time to oral intake was 3.3 days, and the mean period of intravenous analgesic use was 5.0 days. There were no statistically significant differences between single-site and multiport cases. CONCLUSIONS Single-site laparoscopic surgery is technically feasible in inflammatory bowel disease. The length of stay and period of intravenous analgesic use (in days) appear to be higher than those in comparable series examining outcomes of single-site laparoscopic colorectal surgery, and the outcomes are comparable with those of multiport laparoscopy. This may be because of the nature of inflammatory bowel disease, limiting the benefits of a single-site approach in this population.

INTRODUCTION: Guidelines recommend using a pulse oximeter rather than arterial blood gas (ABG) for COVID\19 patients. However, significant differences can be observed between oxygen saturation measured by pulse oximetry (SpO(2)) and arterial oxygen saturation (SaO(2)) in some clinical conditions. We aimed to assess the reliability of the pulse oximeter in patients with COVID\19. METHODS: We retrospectively reviewed ABG analyses and SpO(2) levels measured simultaneously with ABG in patients hospitalised in COVID\19 wards. RESULTS: We categorised total 117 patients into two groups, in whom the difference between SpO(2) and SaO(2) was 4% (acceptable difference) and >4% (large difference). A large difference group exhibited higher neutrophil count, C\reactive protein, ferritin, fibrinogen, D\dimer and lower lymphocyte count. Multivariate analyses revealed that increased fibrinogen, increased ferritin and decreased lymphocyte count were independent risk factors for a large difference between SpO(2) and SaO(2). The total study group demonstrated the negative bias of 4.02% with the limits of agreement of ?9.22% to 1.17%. The bias became significantly higher in patients with higher ferritin, fibrinogen levels and lower lymphocyte count. CONCLUSION: Pulse oximeters may not be sufficient to assess actual oxygen saturation, especially in COVID\19 patients with high ferritin and fibrinogen levels and low lymphocyte count with low SpO(2) measurements.

Conventionally, eukaryotic mRNAs were thought to be monocistronic, leading to the translation of a single protein. However, large-scale proteomics have led to a massive identification of proteins translated from mRNAs of alternative ORF (AltORFs), in addition to the predicted proteins issued from the reference ORF or from ncRNAs. These alternative proteins (AltProts) are not represented in the conventional protein databases and this ghost proteome was not considered until recently. Some of these proteins are functional and there is growing evidence that they are involved in central functions in physiological and physiopathological context. Based on our experience with AltProts, we were interested in finding out their interaction with the viral protein coming from the SARS-CoV-2 virus, responsible for the 2020 COVID-19 outbreak. Thus, we have scrutinized the recently published data by Krogan and coworkers (2020) on the SARS-CoV-2 interactome with host cells by affinity purification in co-immunoprecipitation (co-IP) in the perspective of drug repurposing. The initial work revealed the interaction between 332 human cellular reference proteins (RefProts) with the 27 viral proteins. Re-interrogation of this data using 23 viral targets and including AltProts, followed by enrichment of the interaction networks, leads to identify 218 RefProts (in common to initial study), plus 56 AltProts involved in 93 interactions. This demonstrates the necessity to take into account the ghost proteome for discovering new therapeutic targets, and establish new therapeutic strategies. Missing the ghost proteome in the drug metabolism and pharmacokinetic (DMPK) drug development pipeline will certainly be a major limitation to the establishment of efficient therapies.