Identifying organizational requirements for the implementation of Advanced Manufacturing Technologies (AMT)

AMT selection and adoption processes have been extensively studied. Topics that include financial and human factors, productivity, and coordination of the AMT implementation establish a substantial content of the present research agenda. The purpose of this paper is to study the organizational factors that influence the AMT implementation, considering a manufacturing strategy context and an analysis based on an organizational design framework. The research strategy is based on ‘empirical iterations’ using survey secondary data, experts’ interviews information and multiple case studies. The results show that there is a set of recommendations, which strongly influence the AMT implementation. Companies require a structured and integrative approach for the AMT implementation in order to take advantage of all their individual and systemic benefits. The set of proposed AMT recommendations for integrating these technologies to the organizational design are framed by structural, process and contextual aspects.     

Substrate Activity Screening (SAS) and Related Approaches in Medicinal Chemistry

Substrate activity screening (SAS) was presented a decade ago by Ellman and co‐workers as a straightforward methodology for the identification of fragment‐sized building blocks for enzyme inhibitors. Ever since, SAS and variations derived from it have been successfully applied to the discovery of inhibitors of various families of enzymatically active drug targets. This review covers key achievements and challenges of SAS and related methodologies, including the modified substrate activity screening (MSAS) approach. Special attention is given to the kinetic and thermodynamic aspects of these methodologies, as a thorough understanding thereof is crucial for successfully transforming the identified fragment‐sized hits into potent inhibitors.     

COVID-19 and Lung Mast Cells: The Kallikrein–Kinin Activation Pathway

Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein–kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE⁺ MCs, tryptase⁺ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient.     

The Association between Gut Microbiota and Osteoarthritis: Does the Disease Begin in the Gut?

Some say that all diseases begin in the gut. Interestingly, this concept is actually quite old, since it is attributed to the Ancient Greek physician Hippocrates, who proposed the hypothesis nearly 2500 years ago. The continuous breakthroughs in modern medicine have transformed our classic understanding of the gastrointestinal tract (GIT) and human health. Although the gut microbiota (GMB) has proven to be a core component of human health under standard metabolic conditions, there is now also a strong link connecting the composition and function of the GMB to the development of numerous diseases, especially the ones of musculoskeletal nature. The symbiotic microbes that reside in the gastrointestinal tract are very sensitive to biochemical stimuli and may respond in many different ways depending on the nature of these biological signals. Certain variables such as nutrition and physical modulation can either enhance or disrupt the equilibrium between the various species of gut microbes. In fact, fat-rich diets can cause dysbiosis, which decreases the number of protective bacteria and compromises the integrity of the epithelial barrier in the GIT. Overgrowth of pathogenic microbes then release higher quantities of toxic metabolites into the circulatory system, especially the pro-inflammatory cytokines detected in osteoarthritis (OA), thereby promoting inflammation and the initiation of many disease processes throughout the body. Although many studies link OA with GMB perturbations, further research is still needed.     

Increase in energy and land use by a bio-based chemical industry

About 80% of the chemical products are still based on crude oil. Bio-based materials will increasingly gain importance. As the fraction of oxygen is normally higher in biomass than in crude oil as well as in the derived conventional products, this implies a need to develop new synthesis pathways. Depending on the types of new synthesis pathways, the effects of a complete raw-material change on land and exergy use differ. Here, different synthesis pathways starting from glucose and plant oil to different kinds of end products are evaluated utilizing material and exergy balances. These evaluations are carried out under today's and future conditions and constraints, like yield, demand of organic chemicals and world population. The analysis in this paper shows that the land and energy use can be significantly reduced, if the products are adapted to the chemical structure of their bio-based feedstock.     

Hydrophobic methacrylic copolymers containing azobenzene moieties

The functionalization of polymer materials to produce hydrophobic surfaces is an important goal for a number of applications, especially those associated with self-cleaning and anti-adherent surfaces. Azopolymers are known for photoisomerization property that can lead to photoinduced anisotropy, photomechanical effect and surface modification with surface-relief gratings. In this study, we combine the low surface energy property of perfluoroalkyl methacrylates with the photoinduced characteristics of azopolymers, by fabricating cast films of copolymers of 2,2,2 trifluorethyl methacrylate (TFEMA) or 2,2,3,3,4,4,5,5 octafluoropentyl methacrylate (OFPMA) and 4′-[N-ethyl-N-(2methacryloxy-ethyl)]amine-4-nitro-azobenzene (DR13MA). The intended structures of the copolymers synthesized using radicalar polymerization was confirmed with Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance (NMR). The polymers had much higher thermal stability than conventional azopolymers, and formed hydrophobic surfaces with a water contact angle of ca. 96°. These hydrophobic azopolymers were amenable to the formation of surface-relief gratings at room temperature resulting from an all-photonic mass transport process, which opens the way for a number of new applications to be designed.     

High prevalence of subclinical hypothyroidism and nodular thyroid disease in patients on hemodialysis

Chronic kidney disease has been known to affect thyroid hormone metabolism. Low serum levels of T3 and T4 are the most remarkable laboratorial findings. A high incidence of goiter and nodules on thyroid ultrasonography has been reported in patients with end‐stage renal disease (ESRD). Our objective is to evaluate the prevalence of laboratorial and morphologic alterations in the thyroid gland in a cohort of patients with ESRD on hemodialysis (HD). Sixty‐one patients with ESRD on HD were selected and compared with 43 healthy subjects matched by age, gender, and weight. Patients were submitted to thyroid ultrasonography. T3, free T4 (FT4), thyroid‐stimulating hormone, antithyroglobulin, and antithyroperoxidase antibodies were measured. The mean age of patients with ESRD was 47.4 ± 12.3 and 61% were women. ESRD was mainly caused by hypertensive nephrosclerosis and diabetic nephropathy. Mean thyroid volume, as determined by ultrasonography, was similar in both groups. Patients with ESRD had more hypoechoic nodules when compared with the control group (24.1% vs. 7.9%, P = 0.056). Mean serum FT4 and T3 levels were significantly lower in patients with ESRD, and subclinical hypothyroidism was more prevalent in patients with ESRD (21.82% vs. 7.14% control group, P = 0.04). Titers of antithyroid antibodies were similar in both groups. ESRD was associated with a higher prevalence of subclinical hypothyroidism and lower levels of T3 and FT4. Almost a quarter of patients showed thyroid nodules >10 mm. Periodic ultrasound evaluation and assessment of thyroid function are recommended in patients with ESRD on HD.     

Alterations in phenolic compound levels and antioxidant activity in response to cooking technique effects: A meta-analytic investigation

The aim of this study was to review prior studies that have evaluated the effects of cooking techniques on polyphenol levels and antioxidant activity in vegetables and to release a meta-analysis of the findings. Meta-analysis with a random effect model was conducted using the weighted response ratios (R*) that were calculated for each experiment. Baking (R* = 0.51), blanching (R* = 0.94), boiling (R* = 0.62), microwaving (R* = 0.54) and pressure cooking (R* = 0.47) techniques precipitated significant reductions in the polyphenol levels. Significant decreases in the antioxidant activity levels were noted after baking (R* = 0.45) and boiling (R* = 0.76), while significant increases were observed after frying (R* = 2.26) and steaming (R* = 1.52).