Semisolid extrusion 3D printing of Dolutegravir-Chitosan nanoparticles laden polymeric buccal films: personalized solution for pediatric treatment.

In this work, the semi solid extrusion 3D printing process was utilized to incorporate anti-HIV drug Dolutegravir and its nanoparticles into the buccal film (BF) that was fabricated using the developed polymer ink. The composite made of polyvinyl alcohol (PVA) and sodium alginate was processed into a 3D printing polymer ink with optimum viscosity (9587 ± 219 cP) needed for the seamless extrusion through the nozzle of the 3D printer. The formulated BFs were assessed for its physical properties like weight (0.414 ± 0.3 g), thickness (1.54 ± 0.02 mm), swelling index (18.5 ± 0.91%), and mucoadhesiveness strength (0.165 ± 0.09 N) etc, The structural integrity and the surface morphology of the developed BFs were investigated by scanning electron microscopy analysis. The chemical stability and the solid-state nature of the drug in the BFs were assessed by Fourier transform infrared and x-ray diffraction analysis respectively. Further the BFs were assessed for drug dissolutionin-vitroandex-vivo, to study the effect of polymer composition and printing condition on the dissolution profile of the drug in the simulated salivary fluid. The results demonstrated that the developed PVA based polymer ink for 3D printing utilizing pressure is a versatile approach in the context of manufacturing mucoadhesive BFs customized in terms of shape and the amount of drug loaded.

Development of an anti-infective urinary catheter composed of polyvinyl alcohol/sodium alginate/methylcellulose/polyethylene glycol by using a pressure-assisted 3D-printing technique.

Catheter-associated urinary tract infections (CAUTI) are a common complication associated with catheterization, leading to urosepsis, bacteriuria, and septicaemia. The present work focuses on 3D printing a urinary catheter with anti-infective properties using various concentrations of polyvinyl alcohol (PVA, e.g., 6-8 %), sodium alginate (NaAlg, e.g. 1-4 %), methylcellulose (MC, 5 %), polyethylene glycol (PEG, 5 %) impregnated with secnidazole, an antibiotic acting against Gram-negative bacteria. To produce suitable polymer ink for Pressure Assisted Microsyringe (PAM) 3D printing, the cross-linked between NaAlg and calcium chloride is necessary to prepare the catheter. The optimised catheter was found to have an outer diameter of 5 mm, an inner diameter of 3.5 mm, and a length of the catheter of 50 mm. The analysis by various methods confirms the successful incorporation of secnidazole in the 3D-printed catheter. A drug-loaded/coated catheter showed an initial drug release of 79 % following a sustained release to reach 100 % within 5 h. Weibull model fits well with the drug release data. The release models suggest the Quasi-Fickian diffusion mechanism from the system. Moreover, the secnidazole 3D printed catheter disrupted biofilms and suppressed all the Quorum sensing mediated virulence factors of two important keystone pathogens causing urinary tract infections.

Muffins and Meditation: Combatting Burnout in Surgical Residents.

OBJECTIVE: To quantify the prevalence of burnout in our surgical residency program and to assess the impact of a weekly wellness program for surgical residents through validated tools measuring mindfulness, self-compassion, flourishing, and burnout. Our hypothesis was that participants with more frequent attendance would: (1) be more mindful and self-compassionate and (2) experience less burnout and more flourishing. DESIGN: An optional one-hour weekly breakfast conference was facilitated by a senior surgical faculty member with the time protected from all clinical duties. Following a guided meditation, participants were given time for reflection and dialogue about their training experiences or led in a wellness exercise. TRANCE (tolerance, respect, anonymity, nonretaliation, compassion, egalitarianism) principles were utilized to create a safe and open environment. Residents were surveyed at the end of the study period, which was from March 2017 through June 2018. SETTING: The conference and data analysis was conducted at Denver Health Medical Center, affiliated with the University of Colorado School of Medicine. PARTICIPANTS: This study analyzed survey responses from 85 surgical residents. RESULTS: Following the wellness program, when answering the 2-question Maslach Burnout Inventory, 35.7% of residents reported feeling burned out by their work once a week or more, and 29.7% reported feeling more callous toward people once a week or more. After multivariate analysis, the only independent predictors of increased burnout were "not being married or in a committed relationship," lower positive affect, and higher negative affect. Written feedback was overwhelmingly positive, and residents expressed gratitude for the conference, the opportunity for self-reflection, and open dialogue with attendings and colleagues. CONCLUSIONS: The prevalence of burnout is high among surgical residents. Allowing time to practice a mindfulness meditation while providing space for residents to share their experiences may be protective, and efforts should be made to reduce barriers to participation.

COVID-19-associated brain abscess caused by Trichosporon dohaense: A case report and review of literature.

We report the first case of Coronavirus Disease 2019 (COVID-19)-associated brain abscess caused by a rare Trichosporon species, T. dohaense. The patient was a known diabetic and had received systemic corticosteroids for the treatment of COVID-19. He underwent craniotomy and evacuation of abscess. The pus aspirate grew a basidiomycetous yeast, morphologically resembling Trichosporon species. The isolate was initially misidentified by VITEK® MS due to lack of mass spectral database of T. dohaense. Accurate identification was achieved by internal transcribed spacer-directed panfungal polymerase chain reaction. The patient had a favorable outcome following surgical intervention and antifungal therapy.

Scoping Review of Intervention Strategies for Improving Coverage and Uptake of Maternal Nutrition Services in Southeast Asia.

Maternal undernutrition can lead to protein-energy malnutrition, micronutrient deficiencies, or anemia during pregnancy or after birth. It remains a major problem, despite evidence-based maternal-nutrition interventions happening on ground. We conducted a scoping review to understand different strategies and delivery mechanisms to improve maternal nutrition, as well as how interventions have improved coverage and uptake of services. An electronic search was conducted in PubMed and Google Scholar for published studies reporting on the effectiveness of maternal-nutrition interventions in terms of access or coverage, health outcomes, compliance, and barriers to intervention utilization. The search was limited to studies published within ten years before the initial search date, 8 November 2019; later, it was updated to 17 February 2021. Of 31 studies identified following screening and data extraction, 22 studies were included for narrative synthesis. Twelve studies were reported from India and eleven from Bangladesh, three from Nepal, two from both Pakistan and Thailand (Myanmar), and one from Indonesia. Nutrition education and counselling, home visits, directly observed supplement intake, community mobilization, food, and conditional cash transfer by community health workers were found to be effective. There is a need to incorporate diverse strategies, including various health education approaches, supplementation, as well as strengthening of community participation and the response of the health system in order to achieve impactful maternal nutrition programs.

Silver Nanomaterials for Wound Dressing Applications.

Silver nanoparticles (AgNPs) have recently become very attractive for the scientific community due to their broad spectrum of applications in the biomedical field. The main advantages of AgNPs include a simple method of synthesis, a simple way to change their morphology and high surface area to volume ratio. Much research has been carried out over the years to evaluate their possible effectivity against microbial organisms. The most important factors which influence the effectivity of AgNPs against microorganisms are the method of their preparation and the type of application. When incorporated into fabric wound dressings and other textiles, AgNPs have shown significant antibacterial activity against both Gram-positive and Gram-negative bacteria and inhibited biofilm formation. In this review, the different routes of synthesizing AgNPs with controlled size and geometry including chemical, green, irradiation and thermal synthesis, as well as the different types of application of AgNPs for wound dressings such as membrane immobilization, topical application, preparation of nanofibers and hydrogels, and the mechanism behind their antimicrobial activity, have been discussed elaborately.

Additive manufacturing of biodegradable porous orthopaedic screw.

Advent of additive manufacturing in biomedical field has nurtured fabrication of complex, customizable and reproducible orthopaedic implants. Layer-by-layer deposition of biodegradable polymer employed in development of porous orthopaedic screws promises gradual dissolution and complete metabolic resorption thereby overcoming the limitations of conventional metallic screws. In the present study, screws with different pore sizes (916 × 918 µm to 254 × 146 µm) were 3D printed at 200 µm layer height by varying printing parameters such as print speed, fill density and travel speed to augment the bone ingrowth. Micro-CT analysis and scanning electron micrographs of screws with 45% fill density confirmed porous interconnections (40.1%) and optimal pore size (259 × 207 × 200 µm) without compromising the mechanical strength (24.58 ± 1.36 MPa). Due to the open pore structure, the 3D printed screws showed increased weight gain due to the deposition of calcium when incubated in simulated body fluid. Osteoblast-like cells attached on screw and infiltrated into the pores over 14 days of in vitro culture. Further, the screws also supported greater human mesenchymal stem cell adhesion, proliferation and mineralized matrix synthesis over a period of 21 days in vitro culture as compared to non-porous screws. These porous screws showed significantly increased vascularization in a rat subcutaneous implantation as compared to control screws. Porous screws produced by additive manufacturing may promote better osteointegration due to enhanced mineralization and vascularization.

From Seabed to Bedside: A Review on Promising Marine Anticancer Compounds.

The marine environment represents an outstanding source of antitumoral compounds and, at the same time, remains highly unexplored. Organisms living in the sea synthesize a wide variety of chemicals used as defense mechanisms. Interestingly, a large number of these compounds exert excellent antitumoral properties and have been developed as promising anticancer drugs that have later been approved or are currently under validation in clinical trials. However, due to the high need for these compounds, new methodologies ensuring its sustainable supply are required. Also, optimization of marine bioactives is an important step for their success in the clinical setting. Such optimization involves chemical modifications to improve their half-life in circulation, potency and tumor selectivity. In this review, we outline the most promising marine bioactives that have been investigated in cancer models and/or tested in patients as anticancer agents. Moreover, we describe the current state of development of anticancer marine compounds and discuss their therapeutic limitations as well as different strategies used to overcome these limitations. The search for new marine antitumoral agents together with novel identification and chemical engineering approaches open the door for novel, more specific and efficient therapeutic agents for cancer treatment.

Rab GTPases: Emerging Oncogenes and Tumor Suppressive Regulators for the Editing of Survival Pathways in Cancer.

The Rab GTPase family of proteins are mediators of membrane trafficking, conferring identity to the cell membranes. Recently, Rab and Rab-associated factors have been recognized as major regulators of the intracellular positioning and activity of signaling pathways regulating cell growth, survival and programmed cell death or apoptosis. Membrane trafficking mediated by Rab proteins is controlled by intracellular localization of Rab proteins, Rab-membrane interactions and GTP-activation processes. Aberrant expression of Rab proteins has been reported in multiple cancers such as lung, brain and breast malignancies. Mutations in Rab-coding genes and/or post-translational modifications in their protein products disrupt the cellular vesicle trafficking network modulating tumorigenic potential, cellular migration and metastatic behavior. Conversely, Rabs also act as tumor suppressive factors inducing apoptosis and inhibiting angiogenesis. Deconstructing the signaling mechanisms modulated by Rab proteins during apoptosis could unveil underlying molecular mechanisms that may be exploited therapeutically to selectively target malignant cells.

Improving resuscitation decisions: a trust-wide initiative.

INTRODUCTION: Treatment escalation plans (TEPs) are important to ensure that every patient has their ceiling of care discussed and documented formally. At Medway Foundation Trust, we introduced TEP forms in September 2016 which are to be completed by the relevant consultant within 24 hours of admission. AIMS AND METHODS: To evaluate whether TEP forms had been effective at improving escalation planning and whether they had a subsequent impact in do not attempt cardiopulmonary resuscitation (DNACPR) decision-making. We carried out three plan-do-study-act cycles over a 2-year period across 100 patients in medicine and surgery. RESULTS: TEP forms were initially found in 66% (66/100) of the patient notes and 34% (34/100) were completed appropriately. There was a 13% relative improvement in resuscitation decision-making, since the introduction of the TEP forms from November 2015 to January 2017. There was also a 12% reduction in inappropriate referrals to critical care during the same period. We decided to revise the TEP form through extensive collaboration and educate all staff members about the importance of escalation planning. This has led to an improvement in TEP discussion and documentation across the entire trust. CONCLUSION: TEPs can be an effective way of considering and communicating ceilings of care. They should encourage doctors to consider DNACPR decisions for patients who otherwise would not have been considered, and therefore may help reduce inappropriate referrals to critical care. The higher completion rates of the new form and increased clarity among staff regarding escalation planning should lead to an improvement in patient safety outcomes and communication between all patients and staff members. We believe it would be feasible to implement our user-friendly TEP form across other National Health Service organisations in order to develop a universal TEP form.

Use of the Bonfils intubating fibrescope in a baby with a severely compromised airway.

We report the successful use of a 2-mm rigid Bonfils intubation endoscope as a rescue device in a 5-week-old baby presenting with an unstable airway due to massive macroglossia and multiple hemorrhagic lymphangiomata compressing the airway and resulting in a Cormack and Lehane grade 4 view. The limited intraoral space rendered it impossible to visualize the laryngeal inlet or insert a laryngeal mask, Glidescope or Airtraq blade into the patient's mouth. A 2-mm Bonfils fibrescope passed easily into the patient's mouth and facilitated a grade 1 view of the laryngeal inlet with subsequent successful intubation at first attempt with a 3.5-mm uncuffed endotracheal tube. There are very few alternatives to rescue such an airway in this age group with this type of pathology and surgical intervention would have been difficult due to the vascular nature of the lesion. Bonfils intubation endoscopes (Karl Storz Endoscopy, Tuttlingen, Germany) are a series of reusable devices consisting of a rigid metal tube with a fixed 40° anterior tip curvature containing a fibreoptic bundle. They are available in three sizes with outside diameters of 2, 3.5, or 5 mm. The advantage of the pediatric 2-mm Bonfils fibrescope is that it allows intubation with a 2.5-mm endotracheal tube. There is a paucity of the literature pertaining to the use of the Bonfils endoscope as a rescue device for intubation of small infants and neonates. In our case, the infant's airway was compromised as a result of a receding mandible, large protruding tongue, glottic distortion, and limited intraoral space. This prevented the use of bulkier rescue airway devices with the potential for traumatic manipulation, which could have lead to rapid deterioration of an already unstable airway. We feel that many clinicians are unaware of the benefits of the Bonfils fibrescope and suggest further studies to increase its use in elective and emergency situations.

Cardiovascular risk profile of asymptomatic healthy young adults with increased carotid artery intima-media thickness: the Bogalusa Heart Study.

OBJECTIVE: The cardiovascular (CV) risk profile of healthy young adults was studied at the extreme 5th percentiles of carotid intima-medial thickness (IMT) as measured by B-mode ultrasonography in different segments of the carotid artery. METHODS: Anthropometric variables, blood pressure, laboratory data, family history health habits were collected from 518 individuals (mean age 32 years). Individuals in the top and bottom 5th percentiles of IMT of carotid bulb or bifurcation area (n = 22) and the common carotid (n = 25) segments were examined for presence of risk factors. Univariate analyses compared the two groups, t tests, and chi-square tests were performed. RESULTS: The common carotid segment top and bottom percentiles of IMT differed with respect to age (p < 0.000), BMI (p < 0.001). In contrast, carotid bulb segment top and bottom percentiles differed with respect to age, (p = 0.001), BMI (p = 0.004), HDL cholesterol (p 0.006), LDL cholesterol (p = 0.023), ECG diagnosis (p = 0.016), smoking status (p = 0.004). The individuals in the top 5th percentile of IMT of the bifurcation area were more obese (BMI > 30), hypertensive (BP > 140/90 or on medications), dyslipidemic (LDL > 130 mg/dl, triglycerides > 150, HDL < 40 mg/dl), and more often had an abnormal ECG, and a history of smoking. CONCLUSION: The observed deleterious effect of CV risk factors on IMT of the carotid artery, a surrogate measure of coronary atherosclerosis, underscores the risk factor profile history in youth. The prevalence of multiple risk factors among those in the top 5th percentile of IMT was significantly higher with respect to the carotid bulb segment only (p = 0.000), suggesting more sensitivity to the risk factor burden compared with the common carotid segment. These observations have important implications in preventive cardiology.