Comparative Evaluation of Different Soft Tissue Coverage Techniques at Immediate Implant Sites: A Cohort Study.

AIM AND OBJECTIVE: To compare the mucosal thickness, width of attached gingiva, and extent of coverage achieved with the usage of connective tissue graft, platelet-rich fibrin (PRF) membrane and buccally advanced flap along with bone grafts in the closure of immediate implant site. MATERIALS AND METHODS: Twenty-one sites requiring immediate implants were randomly divided into three groups of seven samples each. The techniques comprised bone grafting in jumping space along with either buccally advanced flap (group A), PRF membrane (group B), or connective tissue graft (group C) to cover the socket. In each group, the extent of socket coverage, mucosal phenotype, and width of attached mucosa achieved were assessed after 3 months and intercompared with initial measurements to identify the best technique in achieving primary tissue closure of immediate implant sites. RESULTS: Comparative assessment of gain in attached mucosal width had a remarkable difference in all the groups but exhibited no statistical significance among the groups compared. Also, comparative assessment of mucosal thickness and the extent of socket coverage equally indicated a clinical significance among all groups, but failed to achieve any statistical significance. CONCLUSION: All the three techniques were found to be equally effective in achieving additional width of attached mucosa around implants, coverage of mucosa at osteotomy sites, and a thicker mucosal phenotype at implant sites. In comparison with one another, no single technique was found to be advantageous over the other. CLINICAL SIGNIFICANCE: The commonly used three techniques for socket coverage following the immediate implant placement has been proven to be equally effective. Thus, the selection of the technique to meet the objective of complete closure of an extraction socket along with implant platform is left open to operator skill and operation site, which should consider least traumatic and most feasible technique.

Strategic Pentablock Copolymer Nanomicellar Formulation for Paclitaxel Delivery System.

Nanomicelles (NM) enhance solubility and absorption of active pharmaceutical ingredients (APIs). Various polymers and non-polymers are utilized to prepare nanomicellar formulations to achieve high absorption and delivery of drugs. The main purpose of this study was to develop drug-loaded nanomicelles with pentablock copolymers for paclitaxel delivery. Monomers of lactide, ε-caprolactone, and polyethylene-glycol were utilized to prepare pentablock copolymer by ring opening technique. The pentablock nanomicelles (PBNM) were formulated by evaporation and rehydration. Both copolymers and nanomicelles were analyzed by H-NMR, FTIR, and XRD. Nanomicelles were further analyzed for size and zeta potential using dynamic light scattering (DLS) and by H-NMR and TEM. The XRD, FTIR, and H-NMR analyses confirmed the structures of the pentablock copolymers. Average size was 20 nm ± 5.00 nm, and ζ-potential is around zero. H-NMR and FTIR analyses for Paclitaxel-PBNM indicated peaks of paclitaxel and the polymer, confirming successful encapsulation. TEM showed spherical morphology and size range similar to that obtained by DLS. In vitro release studies revealed slow first-order paclitaxel release rate from pentablock nanomicelles in phosphate buffer solution (PBS). Confocal laser scanning microscopy analysis with coumarin-6-loaded in PBNM indicated that pentablock nanomicelles were efficiently taken into prostate cancer (PC-3) cells. Cell proliferation assay showed that nanomicelles were able to ferry adequate amounts of paclitaxel drug into PC-3 cells and subsequently inhibiting PC-3 cell proliferation significantly. Results confirmed that pentablock copolymer can generate drug-loaded nanomicelles with desirable sizes and zeta potential. These demonstrate potentiality of pentablock nanomicelles as carrier for anticancer delivery.

Clear, Aqueous Topical Drop of Triamcinolone Acetonide.

The objective of this study was to develop a clear aqueous mixed nanomicellar formulation (NMF) of triamcinolone acetonide (TA) with a combination of nonionic surfactant hydrogenated castor oil 60 (HCO-60) and octoxynol-40 (Oc-40). In order to delineate the effects of drug-polymer interactions on entrapment efficiency (EE), loading efficiency (LE), and critical micellar concentration (CMC), a design of experiment (DOE) was performed to optimize the formulation. In this study, full-factorial design has been used with HCO-60 and OC-40 as independent variables. All formulations were prepared following solvent evaporation and film rehydration method, characterized with size, polydispersity, shape, morphology, EE, LE, and CMC. A specific blend of HCO-60 and Oc-40 at a particular wt% ratio (5:1.5) produced highest drug EE, LE, and smallest CMC (0.0216 wt%). Solubility of TA in NMF improved 20 times relative to normal aqueous solubility. Qualitative 1H NMR studies confirmed the absence of free drug in the outer aqueous NMF medium. Moreover, TA-loaded NMF appeared to be highly stable and well tolerated on human corneal epithelial cells (HCEC) and human retinal pigment epithelial cells (D407 cells). Overall, these studies suggest that TA in NMF is safe and suitable for human topical ocular drop application.

The low oxygen, oxidative and osmotic stress responses synergistically act through the ethylene response factor VII genes RAP2.12, RAP2.2 and RAP2.3.

The ethylene response factor VII (ERF-VII) transcription factor RELATED TO APETALA2.12 (RAP2.12) was previously identified as an activator of the ALCOHOL DEHYDROGENASE1 promoter::luciferase (ADH1-LUC) reporter gene. Here we show that overexpression of RAP2.12 and its homologues RAP2.2 and RAP2.3 sustains ABA-mediated activation of ADH1 and activates hypoxia marker genes under both anoxic and normoxic conditions. Inducible expression of all three RAP2s conferred tolerance to anoxia, oxidative and osmotic stresses, and enhanced the sensitivity to abscisic acid (ABA). Consistently, the rap2.12-2 rap2.3-1 double mutant showed hypersensitivity to both submergence and osmotic stress. These findings suggest that the three ERF-VII-type transcription factors play roles in tolerance to multiple stresses that sequentially occur during and after submergence in Arabidopsis. Oxygen-dependent degradation of RAP2.12 was previously shown to be mediated by the N-end rule pathway. During submergence the RAP2.12, RAP2.2 and RAP2.3 are stabilized and accumulates in the nucleus affecting the transcription of stress response genes. We conclude that the stabilized RAP2 transcription factors can prolong the ABA-mediated activation of a subset of osmotic responsive genes (e.g. ADH1). We also show that RAP2.12 protein level is affected by the REALLY INTERESTING GENE (RING) domain containing SEVEN IN ABSENTIA of Arabidopsis thaliana 2 (SINAT2). Silencing of SINAT1/2 genes leads to enhanced RAP2.12 abundance independently of the presence or absence of its N-terminal degron. Taken together, our results suggest that RAP2.12 and its homologues RAP2.2 and RAP2.3 act redundantly in multiple stress responses. Alternative protein degradation pathways may provide inputs to the RAP2 transcription factors for the distinct stresses.

The Arabidopsis ZINC FINGER PROTEIN3 Interferes with Abscisic Acid and Light Signaling in Seed Germination and Plant Development.

Seed germination is controlled by environmental signals, including light and endogenous phytohormones. Abscisic acid (ABA) inhibits, whereas gibberellin promotes, germination and early seedling development, respectively. Here, we report that ZFP3, a nuclear C2H2 zinc finger protein, acts as a negative regulator of ABA suppression of seed germination in Arabidopsis (Arabidopsis thaliana). Accordingly, regulated overexpression of ZFP3 and the closely related ZFP1, ZFP4, ZFP6, and ZFP7 zinc finger factors confers ABA insensitivity to seed germination, while the zfp3 zfp4 double mutant displays enhanced ABA susceptibility. Reduced expression of several ABA-induced genes, such as RESPONSIVE TO ABSCISIC ACID18 and transcription factor ABSCISIC ACID-INSENSITIVE4 (ABI4), in ZFP3 overexpression seedlings suggests that ZFP3 negatively regulates ABA signaling. Analysis of ZFP3 overexpression plants revealed multiple phenotypic alterations, such as semidwarf growth habit, defects in fertility, and enhanced sensitivity of hypocotyl elongation to red but not to far-red or blue light. Analysis of genetic interactions with phytochrome and abi mutants indicates that ZFP3 enhances red light signaling by photoreceptors other than phytochrome A and additively increases ABA insensitivity conferred by the abi2, abi4, and abi5 mutations. These data support the conclusion that ZFP3 and the related ZFP subfamily of zinc finger factors regulate light and ABA responses during germination and early seedling development.

Geophagy practices and the content of chemical elements in the soil eaten by pregnant women in artisanal and small scale gold mining communities in Tanzania.

BACKGROUND: Geophagy, a form of pica, is the deliberate consumption of soil and is relatively common across Sub-Saharan Africa. In Tanzania, pregnant women commonly eat soil sticks sold in the market (pemba), soil from walls of houses, termite mounds, and ground soil (kichuguu). The present study examined geophagy practices of pregnant women in a gold mining area of Geita District in northwestern Tanzania, and also examined the potential for exposure to chemical elements by testing soil samples. METHOD: We conducted a cross sectional study using a convenience sample of 340 pregnant women, ranging in age from 15-49 years, who attended six government antenatal clinics in the Geita District, Tanzania. Structured interviews were conducted in June-August, 2012, to understand geophagy practices. In addition, soil samples taken from sources identified by pregnant women practicing geophagy were analysed for mineral element content. RESULTS: Geophagy was reported by 155 (45.6%) pregnant women with 85 (54.8%) initiating the practice in the first trimester. A total of 101 (65%) pregnant women reported eating soil 2 to 3 times per day while 20 (13%) ate soil more than 3 times per day. Of 155 pregnant women 107 (69%) bought pemba from local shops, while 48 (31%) consumed ground soil kichuguu. The estimated mean quantity of soil consumed from pemba was 62.5 grams/day. Arsenic, chromium, copper, iron, manganese, nickel and zinc levels were found in both pemba and kichuguu samples. Cadmium and mercury were found only in the kichuguu samples. Based on daily intake estimates, arsenic, copper and manganese for kichuguu and copper and manganese for pemba samples exceed the oral Minimum Risk Levels designated by the U.S. Agency for Toxic Substance and Disease Registry. CONCLUSION: Almost 50% of participants practiced geophagy in Geita District consistent with other reports from Africa. Both pemba and kichuguu contained chemical elements at varying concentration, mostly above MRLs. As such, pregnant women who eat soil in Geita District are exposed to potentially high levels of chemical elements, depending upon frequency of consumption, daily amount consumed and the source location of soil eaten.

Prevalence of Sarcoptes scabiei infestation and its associated factors among primary school children: A school-based cross-sectional survey in the Rufiji district, Tanzania.

Objectives: This study aimed to investigate the prevalence of Sarcoptes scabiei infestation and its associated factors among primary school children (PSC) in the Rufiji district. Methods: A quantitative school-based cross-sectional study was conducted among 447 PSC in the Rufiji district. The prevalence of scabies among PSC was determined by clinical examination and by microscopic examination of skin samples for the presence of S. scabiei. A structured questionnaire was used to gather data on factors associated with S. scabiei infestation. Descriptive analysis, Fisher's exact, chi-square tests, and logistic regression analysis were used to analyze the data. Results: The prevalence of scabies was 2.0%. Of the assessed factors, only physical contact with a person having itchy skin lesions (Adjusted Odds Ratio [AOR]=4.04, 95%CI 4.39-12.50) and infrequency of changing clothes before laundry (AOR=2.99, 95%CI 1.35-4.94) were significantly associated with scabies. The majority of participants demonstrated low levels of knowledge, with half exhibiting poor attitudes and inappropriate healthcare-seeking behaviors. Conclusions: There was an ongoing transmission of scabies among PSC in the Rufiji district, with the factors associated with the transmission being physical contact with a person who had an itchy skin lesion and the infrequency of changing clothes before laundry. Therefore, there is a need for regular clinical screening and treatment of positive cases with preventive measures on contact and provision of health education.

Exploring the feasibility of pupillometry training and perceptions of potential use for intracranial pressure monitoring in Uganda: A mixed methods study.

INTRODUCTION: Traumatic brain injury (TBI) accounts for the majority of Uganda's neurosurgical disease burden; however, invasive intracranial pressure (ICP) monitoring is infrequently used. Noninvasive monitoring could change the care of patients in such a setting through quick detection of elevated ICP. PURPOSE: Given the novelty of pupillometry in Uganda, this mixed methods study assessed the feasibility of pupillometry for noninvasive ICP monitoring for patients with TBI. METHODS: Twenty-two healthcare workers in Kampala, Uganda received education on pupillometry, practiced using the device on healthy volunteers, and completed interviews discussing pupillometry and its implementation. Interviews were assessed with qualitative analysis, while quantitative analysis evaluated learning time, measurement time, and accuracy of measurements by participants compared to a trainer's measurements. RESULTS: Most participants (79%) reported a positive perception of pupillometry. Participants described the value of pupillometry in the care of patients during examination, monitoring, and intervention delivery. Commonly discussed concerns included pupillometry's cost, understanding, and maintenance needs. Perceived implementation challenges included device availability and contraindications for use. Participants suggested offering continued education and engaging hospital leadership as implementation strategies. During training, the average learning time was 13.5 minutes (IQR 3.5), and the measurement time was 50.6 seconds (IQR 11.8). Paired t-tests to evaluate accuracy showed no statistically significant difference in comparison measurements. CONCLUSION: Pupillometry was considered acceptable for noninvasive ICP monitoring of patients with TBI, and pupillometer use was shown to be feasible during training. However, key concerns would need to be addressed during implementation to aid device utilization.

A Mixed-Methods Assessment of the Feasibility of Conducting Neurosurgical Clinical Research in Uganda.

BACKGROUND: Clinical research is necessary to evaluate neurosurgical interventions, yet clinical trials are conducted less frequently in low- and middle-income countries. Because specific barriers, facilitating factors, and strategies for neurosurgical clinical research in Uganda have not been previously identified, this study evaluated neurosurgical providers' perspectives on clinical research and documentation patterns of neurosurgical variables at Mulago National Referral Hospital. METHODS: Retrospective review of 166 neurosurgical patient charts assessed the frequency of documentation of key variables. Twenty-two providers working in neurosurgery participated in 6 focus group discussions with qualitative analysis utilizing the framework method. RESULTS: Chart review showed that primary diagnosis (99.4%), pupil light response (97.6%), and computed tomography scan results (93.3%) were documented for most patients. Cranial nerve exam (61.5%), pupil size (69.9%), and time to neurosurgical intervention (45%) were documented less frequently. On average, Glasgow Coma Scale was documented for 86.6% of days hospitalized, while vital signs were documented for 12.3%. In most focus group discussions, participants identified follow-up, financing, recruitment, time, approval, and sociocultural factors as research barriers. Participants described how the current health workforce facilitates successful research. To improve research capacity, suggested strategies focused on research networks, data collection, leadership, participant recruitment, infrastructure, and implementation. CONCLUSIONS: At Mulago National Referral Hospital, there was variability in the frequency of documentation of neurosurgical variables, which may impact data collection for future studies. While multiple barriers were identified, sociocultural, financing, and time barriers greatly impacted neurosurgical clinical research. Despite that, identified facilitating factors and strategies could be utilized to support neurosurgical research capacity growth.

Non-alcoholic fatty liver disease and diabetic retinopathy: Is there an association?

Background: Studies have not proven whether an association exists between diabetic retinopathy (DR) and non-alcoholic fatty liver disease (NAFLD). The reports from various parts of the world have not used uniform criteria, and hence, results are inconclusive. Both DR and NAFLD are common conditions encountered in primary care. Methods: A total of 130 patients with type 2 diabetes from the medical wards of a tertiary care hospital were enrolled. After documentation of clinical and biochemical data, they underwent ultrasonography (USG) of the abdomen and fibroscan grading of liver. Retinopathy was assessed and classified as per the Early Treatment Diabetic Retinopathy Study. Results: The mean age of the patients included in the study was 46.5+/-8.8 with 55% of the participants being male and 45% female. The mean HbA1c was 7.168+/2.4. The association between DR and hepatic fibrosis was assessed by fibroscan (p 0.003) and USG (p 0.001) and was significant on univariate analysis. Multivariate analysis did not confirm this. There was no association between increasing grades of either condition. Although fibroscan and USG significantly concorded in diagnosing NAFLD, fibroscan diagnosed more cases as compared to USG (83 vs 73). Conclusion: Larger studies should be conducted to conclusively determine the association in order to investigate pathogenetic factors and treatment strategies.

Exploring the Potential of PEG-Heparin Hydrogels to Support Long-Term Ex Vivo Culture of Patient-Derived Breast Explant Tissues.

Breast cancer is a complex, highly heterogenous, and dynamic disease and the leading cause of cancer-related death in women worldwide. Evaluation of the heterogeneity of breast cancer and its various subtypes is crucial to identify novel treatment strategies that can overcome the limitations of currently available options. Explant cultures of human mammary tissue have been known to provide important insights for the study of breast cancer structure and phenotype as they include the context of the surrounding microenvironment, allowing for the comprehensive exploration of patient heterogeneity. However, the major limitation of currently available techniques remains the short-term viability of the tissue owing to loss of structural integrity. Here, an ex vivo culture model using star-shaped poly(ethylene glycol) and maleimide-functionalized heparin (PEG-HM) hydrogels to provide structural support to the explant cultures is presented. The mechanical support allows the culture of the human mammary tissue for up to 3 weeks and prevent disintegration of the cellular structures including the epithelium and surrounding stromal tissue. Further, maintenance of epithelial phenotype and hormonal receptors is observed for up to 2 weeks of culture which makes them relevant for testing therapeutic interventions. Through this study, the importance of donor-to-donor variability and intra-patient tissue heterogeneity is reiterated.

An exploration of technology acceptance among nursing faculty teaching online for the first time at the onset of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has brought to the forefront the importance for schools of nursing to use creative and innovative tools that are of high quality and accessible to learners. Faculty who may have been resistant to teaching online prior to the pandemic, no longer had the option to teach face-to-face and were mandated to teach online despite any apprehensions they may have had. PURPOSE: The purpose of this study was to learn more about faculty attitudes and acceptance of teaching online by applying the Technology Acceptance Model to nursing faculty teaching online for the first time during the COVID-19 pandemic. METHODS: This descriptive-correlational study used an online survey tool to explore factors related to technology acceptance among nursing faculty teaching online for the first time during the COVID-19 pandemic. A sample of 87 full-time and part-time nursing faculty completed an adapted version of the Faculty Acceptance Survey. RESULTS: Findings from this study revealed an overall enjoyment of teaching online, confidence in online teaching skills and comfort with technology. However, findings also indicated struggles with workload balance, inferior interactions with students and the need for additional support. CONCLUSION: Findings from this study demonstrate that nursing faculty are generally accepting of technology and positive outcomes are possible if identified concerns are addressed and positive feelings are fostered and supported.

Clinical profile and ophthalmological manifestations of idiopathic intracranial hypertension in adults at a tertiary care center in India: A cross-sectional study.

Purpose: Our aim was to describe the clinical profile of patients with idiopathic intracranial hypertension (IIH), assess ophthalmological manifestations, and correlate grade of papilledema with optic nerve sheath diameter (ONSD) and cerebrospinal fluid (CSF) opening pressure. Methods: This was a prospective cross-sectional study. Patients between 18 and 60 years, diagnosed with IIH using modified Dandy criteria were included. Demographic details, ocular symptoms and signs were noted and papilledema graded. Ocular investigations such as B-scan ONSD and perimetry findings were noted for analysis. Results: The study included 32 patients of mean age 35.25(±9.57) years with a predominantly female population (96.9%). Mean BMI was 28.12(±5.32) kg/m2. Common presenting complaint was headache (87.5%). The most common gynecological disorder was dysmenorrhea (15.6%). Vitamin D deficiency (46.9%) was a biochemical abnormality seen. Most patients had BCVA 6/6 (62.5%). Lateral rectus palsy was present in 12.5%. Papilledema was present in 81.3% eyes with 31.3% Grade I. There was visual field loss in 53.1%, with 20.3% Grade I. Mean CSF opening pressure was 376.3(±191.51) mmH2O. MRI showed empty sella (34.4%) and tortuous optic nerve (18.8%). MRV showed transverse sinus stenosis (52.4%) as common abnormality. There was significant correlation between grade of papilledema and B-scan ONSD. No correlation was seen between CSF opening pressure and ONSD, grade of papilledema and grade of visual field defect and CSF opening pressure with BMI. Conclusion: Clinical profile of patients with IIH was an overweight female of child-bearing age with headache. Visual field examinations are essential in management and follow-up. B-scan ONSD is useful to quantify raised ICP.

A narrative review of the protective effects of curcumin in treating ischemia-reperfusion injury.

Background and Objective: Ischemia-reperfusion (IR) injury is the cause of morbidity and mortality in a variety of diseases and surgical procedures including organ transplantation surgeries, acute coronary syndrome, strokes, and limb injuries. IR injury causes dysfunction of tissues and organs, and oxidative stress plays an important role in driving this process. Curcumin (CUR), a polyphenolic compound derived from turmeric, protects against IR injury by alleviating oxidative stress, reactive oxygen species (ROS) inflammation, apoptosis, and fibrosis. We review the protective effects of CUR against IR. Methods: We searched PubMed, ScienceDirect, and Web of Science databases using the keywords: ischemic reperfusion, CUR and summarized the results. Key Content and Findings: The effects of CUR during IR have been reported for animal models in vitro and in vivo and the compound has been shown in various organs by suppression of oxidative stress, prevention of inflammation, inhibition of apoptosis and autophagy. CUR with nanocarriers showed many advantages than free CUR in the treatment of IR injury, such as improved bioavailability, sustained-release, better water solubility, better target organ accumulation, improved permeability across the blood-brain-barrier and more effective. Conclusions: Nanotechnology offers significant improvements and promising strategies to improve drug delivery to IR-injured tissues and achieve the desired protective effects. Thus, it is necessary to promote further clinical trials to promote the clinical application of CUR with nanocarriers.

Elevated serum AST and LDH levels are associated with infant death in premature babies with neonatal leukemoid reaction: a cohort study.

Background: Neonatal leukemoid reaction (NLR) is often accompanied by infectious or non-infectious diseases, a low birth weight, sepsis, prematurity, ventricular hemorrhage, and bronchial dysplasia. It has an incidence rate of 1.3-15% and a mortality rate of about 41.4%. Previous studies on NLR have largely focused on its pathogenesis and clinical cases, but little is known about its prognostic laboratory indicators. We found that some of the NLR exhibited obviously elevation in liver function tests like aspartate transaminase (AST) and lactate dehydrogenase (LDH) which were not took by all the LR infants. The necessity for liver function tests for the prognosis of NLR was still unclear. Methods: A total of 39 premature infants with NLR at the First Hospital of Jilin University between March 2016 and March 2017 were included in this retrospective cohort study. The infants were divided into death and cured group based on the clinical outcomes. Premature infants with LR and death were defined as the case group (n=14), while infants without death were defined as the control group (n=25). Confounding factors such as age and gender between the two groups were controlled. Blood routine tests, including the white blood cell (WBC) count and subtypes, and liver function, and clinical features were recorded and analyzed. T tests were used to examine the differences in the laboratory indicators between the NLR and control groups. Receiver operating characteristic curves (ROCs) and areas under the curve (AUCs) were used to examine laboratory indicators for prognosis. Results: For predicting clinical outcomes, the ROC curves showed that the cut-off values for AST and LDH were 279 and 1,412 U/L, respectively. The sensitivity and specificity for AST were 92% and 71.43%, respectively, with an AUC of 0.894, while the sensitivity and specificity for LDH were 88% and 78.57%, respectively, with an AUC of 0.911. Conclusions: This innovative study investigated the NLR prognosis depending on laboratory tests. We found that serum AST and LDH levels had reliable predictive value in determining adverse outcomes of NLR.

Discrete responses of erythrocytes, platelets, and von Willebrand factor to shear.

Despite decades of technological advancements in blood-contacting medical devices, complications related to shear flow-induced blood trauma are still frequently observed in clinic. Blood trauma includes haemolysis, platelet activation, and degradation of High Molecular Weight von Willebrand Factor (HMW vWF) multimers, all of which are dependent on the exposure time and magnitude of shear stress. Specifically, accumulating evidence supports that when blood is exposed to shear stresses above a certain threshold, blood trauma ensues; however, it remains unclear how various constituents of blood are affected by discrete shears experimentally. The aim of this study was to expose blood to discrete shear stresses and evaluate blood trauma indices that reflect red cell, platelet, and vWF structure. Citrated human whole blood (n = 6) was collected and its haematocrit was adjusted to 30 ± 2% by adding either phosphate buffered saline (PBS) or polyvinylpyrrolidone (PVP). Viscosity of whole blood was adjusted to 3.0, 12.5, 22.5 and 37.5 mPa·s to yield stresses of 3, 6, 9, 12, 50, 90 and 150 Pa in a custom-developed shearing system. Blood samples were exposed to shear for 0, 300, 600 and 900 s. Haemolysis was measured using spectrophotometry, platelet activation using flow cytometry, and HMW vWF multimer degradation was quantified with gel electrophoresis and immunoblotting. For tolerance to 300, 600 and 900 s of exposure time, the critical threshold of haemolysis was reached after blood was exposed to 90 Pa for 600 s (P < 0.05), platelet activation and HMW vWF multimer degradation were 50 Pa for 600 s and 12 Pa for 300 s respectively (P < 0.05). Our experimental results provide simultaneous comparison of blood trauma indices and thus also the relation between shear duration and magnitude required to induce damage to red cells, platelets, and vWF. Our results also demonstrate that near-physiological shear stress (<12 Pa) is needed in order to completely avoid any form of blood trauma. Therefore, there is an urgent need to design low shear-flow medical devices in order to avoid blood trauma in this blood-contacting medical device field.

An inhibitor of Bcl-2 family proteins induces regression of solid tumours.

Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L) and Bcl-2, are overexpressed in many cancers and contribute to tumour initiation, progression and resistance to therapy. Bcl-X(L) expression correlates with chemo-resistance of tumour cell lines, and reductions in Bcl-2 increase sensitivity to anticancer drugs and enhance in vivo survival. The development of inhibitors of these proteins as potential anti-cancer therapeutics has been previously explored, but obtaining potent small-molecule inhibitors has proved difficult owing to the necessity of targeting a protein-protein interaction. Here, using nuclear magnetic resonance (NMR)-based screening, parallel synthesis and structure-based design, we have discovered ABT-737, a small-molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w, with an affinity two to three orders of magnitude more potent than previously reported compounds. Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation. ABT-737 exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells, and in animal models, ABT-737 improves survival, causes regression of established tumours, and produces cures in a high percentage of the mice.

Validation of Artificial Intelligence Algorithm in the Detection and Staging of Diabetic Retinopathy through Fundus Photography: An Automated Tool for Detection and Grading of Diabetic Retinopathy.

PURPOSE: Diabetic retinopathy (DR) is one of the leading causes of vision loss globally, and early detection plays a significant role in the prognosis. Several studies have been done on the single field fundus photography and artificial intelligence (AI) in DR screening using standardized data sets in urban outpatient settings. This study was carried out to validate AI algorithm in the detection of DR severity using fundus photography in real-time rural setting. METHODS: This cross-sectional study was carried out among 138 patients who underwent routine ophthalmic examination, irrespective of their diabetic status. The participants were subjected to a single field color fundus photography using nonmydriatic fundus camera. The images acquired were processed by AI algorithm for image quality, presence and refer ability of DR. The results were graded by four ophthalmologists. Interobserver variability between the four observers was also calculated. RESULTS: Of the 138 patients, 26 patients (18.84%) had some stage of DR, represented by 47 images (17.03%) positive for signs of DR. All 26 patients were immoderate or severe stage. About 6.5% of the images were considered as not gradable due to poor optical quality. The average agreement between pairs of the four graders was 95.16% for referable DR (RDR). The AI showed 100% sensitivity in detecting DR while the specificity for RDR was 91.47%. CONCLUSION: AI has shown excellent sensitivity and specificity in RDR detection, at par with the performance of individual ophthalmologists and is an invaluable tool for DR screening.