A common perception about Multidisciplinary team (MDT) approach is that it improves quality of care to hospitalized patients, particularly those who are dying. However, there is paucity of information on challenges in implementing such approach in end-of-life care (eolc). The present study explores barriers to MDT functioning in the context of ‘eolc’. Data collected through interviews of physicians, nurses and other staff, and review of case records of deceased patients of a multispecialty hospital in Kolkata (India) suggest that the MDT approach fails to live up to its rhetoric. One of the major challenges is professional boundary that is intrinsic to MDT. Due to this, specialist physicians fail to make consensus end-of-life decisions by overcoming disciplinary boundaries. Moreover, holistic caregiving is compromised in the physician-dominant medical team, where nurses and other non-clinical caregivers feel marginalized. The hospital environment is also not conducive to multidisciplinary teamwork. Application of a disease-specific treatment protocol in ‘eolc’ settings aggravates team coordination. ‘Eolc’ referrals and care transfers becomes very difficult. Dying patients and their families are specially affected by such discordant care. Based on the findings, the study suggests that while team approach is imperative to effective ‘eolc’, there is a need to shift focus from multidisciplinary to transdisciplinary approach to enhance care integration and patient-centric care to terminally ill patients.

Rationale and objective: Occupation-based practice (OBP) is a treatment approach unique to occupational therapy. It harnesses the power of occupation to achieve health and well-being. Most hand therapists are occupational therapists, however, current hand therapy treatment methods are component-based, focussing on physical impairments. This is despite an emerging body of evidence that supports the effectiveness of OBP with hand conditions. To explore the use of OBP in hand therapy, the knowledge, attitudes and practices (KAP) of South African occupational therapists towards OBP needed to be first established. There was no contextually-relevant instrument for this, thus this paper reports on the development processes of a new instrument to capture KAP in OBP in South African hand therapists. Method: Questionnaire development followed the Burns et al (2008) methodology. Items were identified following a comprehensive literature search. Face and content validity, clinical utility, and validation of the subsequent Afrikaans translation were undertaken by two purposively-selected sets of participants (experts and peers). Data collection involved cognitive interviewing, iterative email correspondence, face-to-face discussions, and member checking. Final adjustments to questionnaire wording were made through consensus discussion between the first and second authors. Results: Four therapists participated. Seventy-nine questionnaire items were retained, with three items being removed as they were unclear, or did not measure constructs appropriately for context. The final survey instrument had face and content validity and consisted of 63 KAP items and 16 demographic questions. Conclusion: This is believed to be the first instrument designed to capture valid information on KAP in OBP in hand therapy in South Africa. It will assist in identifying gaps in practice quality, and underpin design of effective strategies for education about, and implementation of, OBP within hand therapy. The instrument is suitable for adaptation to other fields of occupational therapy practice in South Africa, and internationally.

In district Haripur, KPk, Pakistan Treepie Dendrocitta vagabunda parvula (Latham, 1790) (Passeriformes: Corvidae), is a widespread resident bird commonly found. Feeding and Food habits of Treepie were studied by direct focal observation method analysis of gut content and faecal matter. Treepie prefers tree and cultivation areas insects for foraging activities, feeding on animal and plant is an omnivore items ranging from vertebrate species to invertebrate. Feeding upon like red palm weevil, grasshopper, cockroaches, banana stem weevil, nestlings of squirrel and house rat, it feeds up on many pests of agricultural crops Treepie is an important biocontrol agent in the agro ecosystem of the region

Continuous improvements of cell-free synthesis (CFS) systems have generated interest in adopting the technology for the manufacture of biologics. This paper provides an evaluation of the manufacturing cost-effectiveness of CFS for a range of commercial scenarios. The evaluation was performed using an advanced techno-economic engine (TEE) built in Python. The TEE is programmed in an object-oriented environment capable of simulating a plethora of process flowsheets and predicting size and cost metrics for the process and the facility. A case study was formulated to compare the economics of whole bioprocesses based on either a CFS system or a mammalian cell system (CHO) for the manufacture of an antibody drug conjugate (ADC) at different commercial product demand levels (100 – 1000kg/year). The analysis demonstrated the potential of CFS for the commercial manufacture of biologics and identified key cost drivers related with the system. The CFS system showed approximately a two-fold increase in the cost of goods compared to CHO with a significant cost attributed to the in-house manufacture of the bacterial cell extract, necessary for the CFS reaction step in the process. A sensitivity and target analysis highlighted the impetus for further process improvements especially in the titre for the CFS process to become more competitive against well-established systems.

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An unusual cause of spontaneous hypoglycemia is Insulin Autoimmune Syndrome (IAS) or Hirata Disease, characterized by high levels of insulinemia and circulating autoantibodies to insulin in subjects without prior insulin administration.To the best of our knowledge, this is the second case of IAS reported from India.

The analysis of environmental DNA (eDNA) allows efficient surveys of freshwater species and is being increasingly used. However, most studies generally have a limited sampling plan. Because different methods are used by different authors, all the data produced with eDNA cannot be easily pooled together for a global overview. Nevertheless, one of the promising perspectives is the standardization of the methods and protocols, for long-term monitoring, early detection of invasive species, and rare species detection. We here present the biggest dataset using eDNA metabarcoding with standardized methods for freshwater bivalves. Sampling was performed mainly in France, with over 350 localities spread over all major basins. Metabarcoding was performed using two new sets of primers, one for the Unionida and one for the Venerida. The species distributions inferred from eDNA sampling are then compared with those currently known. Results give an insight into the valuable data that eDNA analysis can provide if used at a large scale. Some species were found outside of their known range, especially invasive species but also species of conservation interest. Others were found in a surprisingly low number of localities, although currently considered widespread and of no conservation interest. This can be explained by the databases currently used to establish conservation status, which are often biased by including ancient data, shell-only data, and potentially misidentified species. The present study shows that our eDNA metabarcoding approach will be an essential tool to unveil the true species distributions, to better evaluate their status and improve conservation policymaking.

Rationale, aims, and objectives Pharmacological treatment for bronchiolitis is primarily supportive because bronchodilators, steroids, and antibiotics, show little benefit. Clinical studies have suggested that nebulized 3% HS is useful for infants with bronchiolitis. The aim of this study was to evaluate the cost-effectiveness of the HS nebulized in infant bronchiolitis in a middle-income tropical country Methods A decision tree model was used to estimate the cost-effectiveness of the use of nebulized hypertonic saline (3-7%) compared with treatment without hypertonic saline nebulization (control) in bronchiolitis. Cost data were obtained from a retrospective study on bronchiolitis from tertiary centers in Rionegro, Colombia, while utilities were collected from the literature. The analysis was carried out from a societal perspective. Results The control strategy was dominated by HS nebulized group. The expected costs per patient were US$ 200 (CI 95% US$ 178- 222) in the HS nebulized group and US$ 240 (CI 95% US$ 213- 267) in controls. The expected utilities were 0.923 (CI 95% 0.922- 0.924) in the HS nebulized group and 0.91 (CI 95% 0.918- 0.920) in controls. Sensitivity analyses of parameters in the model showed that the cost-effectiveness of HS was only sensitive to the probability of hospitalization. Conclusion The strategy treatment without hypertonic saline nebulization was dominated by the strategy with HS nebulized in infants with bronchiolitis. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other tropical countries.

Background and Purpose. Drug resistance is a major problem in cancer treatment with traditional or targeted therapeutics. Gemcitabine, a traditional chemotherapeutics, is approved for several human cancers and the first line treatment for locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). However, gemcitabine resistance is frequently observed and a major problem in successful treatments of these cancers and the mechanism of gemcitabine resistance remains largely unknown. In this study, we aim to seek new and understand the molecule mechanisms of gemcitabine resistance in PDAC. Experimental Approach. Using whole genome Reduced Representation Bisulfite Sequencing analysis, we investigated a gemcitabine resistant PDAC cell line M3K compared with its parental MiaPaCa-2 cells and the resistance revertant cell line Rev followed by detailed analyses of PDGFD in gemcitabine resistance using MTT survival assay, bisulfite sequencing, Western blot, siRNA knockdown and over-expression. Key Results. We found that 65 genes had reversible methylation changes in their promoters in gemcitabine resistant PDAC cells. One of these genes, PDGFD, was further studied in detail for the reversible methylation change in its promoter and shown to reversibly up-regulate in expression, contribute to gemcitabine resistance in vitro and in vivo via activating STAT3 signaling in both autocrine and paracrine manners. Its expression also positively associates with poor outcome of PDAC patients. Conclusion and Implications. Reversible epigenetic regulation may play an important role in gemcitabine resistance and targeting PDGFD signaling may alleviate gemcitabine resistance for PDAC treatment.

Co-transplantation of MSCs and HSCs has showed controversial results for treatment of GvHD. In this study, the level of predictor factors and GvHD biomarkers have been checked. The co-transplantation of HSCs and MSCs did not show a significant difference compared to the group received MSCs alone.

Objectives: To analyze the current condition of the urgent neurologic in-hospital consultations, which may help junior doctors to manage diseases related to neurology and carry out emergency consultation. Methods: We conducted a retrospective study of urgent neurologic in-hospital consultations in a large tertiary hospital for four consecutive years (Jan 1, 2014 to Dec 31, 2017). Through the electronic medical record system, the clinical data of patients who received in-patient consultation in emergency neurology department were reviewed and analyzed. Results: A total of 1,437 cases (age range 9 to 103 years old with average age 60.3-year old, Male 54.6%) were included in the study, 57.5% of cases met the urgent consultation criteria. The departments applying for urgent consultation involved 29 clinical departments. The most common reasons of urgent consultation were disturbance of consciousness (36.0%), tic/stiffness (13.6%), limb weakness (8%) and mental disorders (5.6%).Urgent consultation diseases were divided into three categories: neurological diseases (77.8%), non-neurological diseases (10.4%), and unknown diseases (11.8%).Common neurological disorders were urgent cerebrovascular disease (33.6%), epilepsy/status epilepticus (15.8%), and metabolic or infection, toxic encephalopathy (14.9%). Conclusions: Most cases of the urgent neurologic consultation met the urgent neurologic consultation criteria. Non-neurologic junior physicians should clinically enrich their knowledge of neurological diseases.

Background & Purpose: The constitutive androstane receptor (CAR) belongs to nuclear receptor superfamily. The administration of CAR agonist TCPOBOP to mice leads to hepatomegaly but the mechanism is unclear. Yes-associated protein (YAP) is a downstream factor of Hippo signaling pathway, which is a potent regulator of organ size and tissue homeostasis. This study examined the role of YAP in CAR-promoted hepatomegaly and liver regeneration. Experimental Approach: The effect of CAR on liver enlargement and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. KI67 and CTNNB1 staining were performed to evaluate the proliferation response and hepatocytes size. The protein levels of YAP and its downstream targets were measured and Co-IP was conducted to explore the protein-protein interaction between CAR and YAP. Key Results: The results suggested TCPOBOP increases the liver/body weight ratio in WT mice and PHx mice. Hepatocytes enlargement occurred around the central vein area, while the number of KI67+ cells increased around portal vein area. The translocation of YAP was induced and its downstream targets were upregulated after CAR activation via TCPOBOP. Co-IP results revealed a potential protein-protein interaction between CAR and YAP. However, CAR-induced hepatomegaly was still observed in Yap-/- mice. Conclusion and Implications: CAR activation promotes hepatomegaly and liver regeneration in part by inducing nuclear translocation of YAP and interaction with YAP pathway, which provides new insights for understanding the physiological functions of CAR, and suggests the potential for manipulation of liver size.

Background: Increasing the use of tobacco by the younger generation has increased in oral cavity tumours. Surgical treatment is radical and results in severe functional morbidity. Using computer-aided designing technology, surgical and rehabilitative planning can be better. We present here our concept of a biomechanical 3D tongue model and its clinical utility in the management of tongue tumours. Methods: Patients diagnosed with Carcinoma of Tongue were included. These patients underwent a pre-operative Magnetic Resonance Imaging (MRI) of the head and neck region at our center. These patients were informed about the use of a 3D biomechanical patient-specific model for treatment planning and execution. Using Materialise Mimics Innovation Suite 19 DICOM data was imported, visualized, edited and segmented. Flashforge ‘Creator-pro’3D Printer was used for 3D Printing. Fused Deposition Modeling (FDM) technology was used to print the tumour and uninvolved tongue in two different colors for easy identification. These patients underwent surgery with the 3D model serving as a guide for margins. Results: Two patients with stage III squamous cell carcinoma of tongue underwent the surgery based on the plan evolved from the 3D model. All the surgical margins were clear. The model helped address the discordance between patient expectations and surgical outcomes. We found that the model aided the reconstructive surgeon to plan the flap volume better and this translated into better rehabilitative outcomes. Discussion and Conclusion: The 3D biomechanical tongue model is a novel concept and may aid in improving our overall treatment outcomes.

BACKGROUND: the outbreak of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 150000 infected individuals and more than 20000 deaths in Italy. Viral acute pneumonitis is the major cause of morbidity and mortality, but there is increasing evidence that COVID-19 patients show a variable degree of vascular complications, due to a possible hypercoagulability status. OBJECTIVE: to report thrombotic events in abdominal and lower-limb arteries of COVID-19 patients (abdominal aorta, superior mesenteric artery, femoral arteries, cardiac, spleen and kidney). METHODS: we retrospectively reviewed our clinical records of patients with confirmed SARS-CoV-2 infection, admitted from March 1st to April 6th, 2020, to a tertiary care center in Brescia, Italy. We selected five patients with major arterial thrombo-embolic manifestations. RESULTS AND CONCLUSION: In our opinion, arterial thrombotic events may be more common in COVID-19 patients than in general population, possibly resulting in rapid worsening of patient conditions.

Objective: Numerous clinical practice guidelines (CPGs) for the corona virus disease 2019 (COVID-19) have been developed since its outbreak. To date, however, the methodological quality of these guidelines has not been fully evaluated. Quality evaluation of the guidelines is to facilitate the clinic practitioners in diagnosis and treatment of the COVID-19. Methods: The evaluation was conducted by searching seven databases and government organizations websites (December 2019 to March 2020). Four assessors assessed the quality of the CPGs independently with the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument. For domain scores (0-100%), >60% were considered of sufficient quality, and >80% of good quality. Results: Of 471 retrieved records, 20 guidelines were included. The median score for the domain of scope and purpose was 56.9% (range 40.3–90.3%) and nine guidelines scored >60%, among which three guidelines scored >80%. The median score for the stakeholder involvement domain was 7% (range 0–65.3%) and only two guidelines scored >60%. Nine guidelines scored 0% in this domain. The median score for the rigour of development domain was 0% (range 0–91.7%) and fourteen guidelines scored 0% in this domain. The median score for the clarity of presentation domain was 30.6% (range 13.9–91.7%) and six guidelines scored >60%, among which three guidelines scored >80%. The median score for the applicability domain was 0% (0–57.3%) and eleven guidelines scored 0% in this domain. The median score for the editorial independence domain was 0% (0–100%): four guidelines scored >80%. Discussions：Three guidelines were recommendable, and four were recommendable with modification in the stakeholder involvement, the rigour of development, and the applicability domains. Our results could contribute to improve development of future guidelines, and affect the reasonable selection and use of guidelines in clinical practice.

Conservation genomics is an important tool to manage threatened species under current biodiversity loss. Recent advances in sequencing technology mean that we can now use whole genomes to investigate demographic history, local adaptation, inbreeding, and more in unprecedented detail. However, for many rare and elusive species only non-invasive samples such as faeces can be obtained, making it difficult to take advantage of whole genome data. We present a method to extract DNA from the mucosal layer of faecal samples to reconstruct high coverage whole genomes using standard laboratory techniques, therefore in a cost-effective and efficient way. We use wild collected faecal pellets collected from wild caribou (Rangifer tarandus), a species undergoing declines in many parts of its range in Canada and subject to comprehensive conservation and population monitoring measures. We compare four faecal genomes to two tissue genomes sequenced in the same run. Quality metrics were similar between faecal and tissue samples with the main difference being the alignment success of raw reads to the reference genome likely due to differences in endogenous DNA content, affecting overall coverage. One of our faecal genomes was only reconstructed at low coverage (1.6X), however the other three obtained between 7 and 15X, compared to 19 and 25X for the tissue samples. We successfully reconstructed high-quality whole genomes from faecal DNA and, to our knowledge, are the first to obtain genome-wide data from wildlife faecal DNA in a non-primate species, representing an important advancement for non-invasive conservation genomics.

Accumulation of β-carotene in Dunaliella salina is highly dependent on light exposure intensity and duration, but quantitative analysis on photon numbers per cell for triggering β-carotene accumulation is not available so far. In this study, experiment results showed that significant β-carotene accumulation occurred with at least 8 hours illumination at 400 µmol photons·m-2·s-1. To quantifying the average number of photons received per cell (APRPC), correlation between light attenuation with light path, biomass concentration, and β-carotene content was built with both Lambert-Beer and Cornet models, and the latter provided a better simulation. With Cornet model, APRPC was calculated and proposed as a parameter for β-carotene accumulation. It was found that once APRPC reached 0.7 µmol photons cell-1, β-carotene accumulation was triggered, and it was saturated at 9.9 µmol photons cell-1. This study showed that APRPC can be used as an important parameter in D. salina cultivation process, to accurately simulate and control β-carotene production.

BACKGROUND AND PURPOSE Neutrophil overactivation is crucial in the pathogenesis of acute lung injury (ALI). Bletinib (3,3′-dihydroxy-2′,6′-bis(p-hydroxybenzyl)-5-methoxybibenzyl), a natural bibenzyl first extracted from Bletilla striata in 1983, has anti-inflammatory, antibacterial, and antimitotic potential. In this study, we evaluated the therapeutic effects of Bletinib in human neutrophilic inflammation and lipopolysaccharide (LPS)-mediated ALI. EXPERIMENTAL APPROACH We assessed integrin expression, superoxide anion production, degranulation, neutrophil extracellular trap (NET) formation, and adhesion in activated human neutrophils through flow cytometry, spectrophotometry, and immunofluorescence microscopy. Moreover, phosphorylation of Src family kinases (SFKs) and downstream proteins was evaluated through immunoblotting. Finally, a murine LPS-induced ALI model was used to investigate the potential therapeutic effects of Bletinib treatment. KEY RESULTS In activated human neutrophils, Bletinib reduced degranulation, respiratory burst, NET formation, adhesion, migration, and integrin expression; suppressed the enzymatic activity of SFKs, including Src, Lyn, Fgr, and Hck; and inhibited the phosphorylation of SFKs as well as Vav and Bruton’s tyrosine kinase (Btk). In our mice with ALI, the pulmonary sections demonstrated considerable amelioration of prominent inflammatory changes, such as haemorrhage, pulmonary oedema, and neutrophil infiltration, after Bletinib treatment. CONCLUSION AND IMPLICATIONS This is the first study to provide evidence that Bletinib regulates neutrophilic inflammation by inhibiting the SFKs–Btk–Vav pathway and that Bletinib ameliorates LPS-induced ALI in mice. Further biochemical optimisation of Bletinib may be a promising strategy for the development of novel therapeutics for inflammatory diseases.