Image-scoring system for umbilical and uterine artery pulsed-wave Doppler ultrasound measurement.

OBJECTIVES: To develop an objective image-scoring system for pulsed-wave Doppler measurement of maternal uterine and fetal umbilical arteries, and evaluate how this compares with subjective assessment. METHODS: As an extension to the INTERGROWTH-21st Project, we developed a scoring system based on six predefined criteria for uterine and umbilical artery pulsed-wave Doppler measurements. Objective evaluation using the scoring system was compared with subjective assessment which consisted of classifying an image as simply acceptable or unacceptable. Based on sample size estimation, a total of 120 umbilical and uterine artery Doppler images were selected randomly from the INTERGROWTH-21st image database. Two independent reviewers evaluated all images in a blinded fashion, both subjectively and using the six-point scoring system. Percentage agreement and kappa statistic were compared between the two methods. RESULTS: The overall agreement between reviewers was higher for objective assessment using the scoring system (agreement, 85%; adjusted kappa, 0.70) than for subjective assessment (agreement, 70%; adjusted kappa, 0.47). For the six components of the scoring system, the level of agreement (adjusted kappa) was 0.97 for anatomical site, 0.88 for sweep speed, 0.77 for magnification, 0.68 for velocity scale, 0.68 for image clarity and 0.65 for angle of insonation. CONCLUSION: In quality assessment of umbilical and uterine artery pulsed-wave Doppler measurements, our proposed objective six-point image-scoring system is associated with greater reproducibility than is subjective assessment. We recommend this as the preferred method for quality control, auditing and teaching. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Formulation and in vitro evaluation of carbopol 934-based modified clotrimazole gel for topical application.

The aim of present study was to enhance topical permeation of clotrimazole gel preparation by using various permeability enhancers such as coconut oil, pistachio oil and sodium lauryl sulphate (SLS). Clotrimazole gel preparations were prepared and optimized by using three factor, five level central composite design. A second-order polynomial equation was generated in order to estimate the effect of independent variables i.e. coconut oil (X1), pistachio oil (X2) and sodium lauryl sulphate (X3) at various dependent variables i.e. flux (Y1), lag time (Y2), diffusion coefficient (Y3), permeability coefficient (Y4), and input rate (Y5) of clotrimazole gel formulations. Ex vivo skin permeation study was performed through rat skin by using modified Franz diffusion cell system. Optimized formulation F8 exhibited highest flux 2.17 µg/cm2/min, permeability coefficient 0.0019 cm/min and input rate 1.543 µg/cm2/min, along with moderate lag time 77.27 min and diffusion coefficient 0.063 cm2/min, which is further supported by anti-fungal activity that exhibited more prominent zone of inhibition against Candida albicans, Aspergillus niger and Mucor. Thus, it can be concluded that permeation of clotrimazole gel was enhanced by various combination of coconut oil, pistachio oil and sodium lauryl sulphate but optimized formulation F8 containing 0.4 ml pistachio oil, 0.8 ml coconut oil and 0.04 g of SLS exhibited more pronounced and promising effect through rat skin.

Amygdala-mediated enhancement of memory for specific events depends on the hippocampus.

Emotional events are often remembered better than neutral events, a type of memory prioritization by affective salience that depends on the amygdala. Studies with rats have indicated that direct activation of the basolateral complex of the amygdala (BLA) can enhance memory for neutral events, and if the activation is brief and temporally targeted, can do so in a way that benefits memories for specific events. The essential targets of BLA activation in the case of event-specific memory enhancement were unknown, but the hippocampus was known to receive direct projections from the BLA and to support memory for events. In the present study, rats received counterbalanced infusions of either muscimol, a GABAA receptor agonist, or saline into the hippocampus prior to performing a novel object recognition memory task during which initial encounters with some of the objects were immediately followed by brief electrical stimulation to the BLA. When memory was tested 1day later in the saline condition, rats remembered these objects well but showed no memory for objects for which the initial encounter had not been followed by BLA stimulation. In contrast, no benefit to memory of BLA stimulation was observed in the muscimol condition. The results indicated that brief activation of the BLA can prioritize memories for events by enhancing memory for some object encounters but not others and that this benefit to memory depends on interactions between the amygdala and the hippocampus.

Purification and characterization of α-galactosidase isolated from Klebsiella pneumoniae in the human oral cavity.

The enzyme α-Galactosidase (α-D-galactoside galactohydrolase [EC 3.2.1.22]) is an exoglycosidase that hydrolyzes the terminal α-galactosyl moieties of glycolipids and glycoproteins. It is ubiquitous in nature and possesses extensive applications in the food, pharma, and biotechnology industries. The present study aimed to purify α-galactosidase from Klebsiella pneumoniae, a bacterium isolated from the human oral cavity. The purification steps involved ammonium sulfate precipitation (70 %), dialysis, ion exchange chromatography using a DEAE-cellulose column, and affinity monolith chromatography. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis was used to determine the molecular weight of the purified enzyme. The kinetic constants, Michaelis constant (Km) and maximal velocity (Vmax), for this enzyme were determined by using p-nitrophenyl-α-D-galactopyranoside as substrate. The results showed that the purification fold, specific activity, and yield were 126.52, 138.58 units/mg, and 21.5 %, respectively. The SDS-PAGE showed that the molecular weight of the purified enzyme was 75 kDa. The optimum pH and temperature of the purified α-galactosidase were detected at pH 6.0 and 50 °C, respectively. The kinetic constants, Michaelis constant (Km) and maximal velocity (Vmax), for this enzyme were 4.6 mM and 769.23 U/ml, respectively. α-galactosidase from Klebsiella pneumoniae was purified and characterized. (SDS-PAGE) analysis showed that the purified enzyme appeared as single band with a molecular weight of 75 kDa.

Refining mutanome-based individualised immunotherapy of melanoma using artificial intelligence.

Using the particular nature of melanoma mutanomes to develop medicines that activate the immune system against specific mutations is a game changer in immunotherapy individualisation. It offers a viable solution to the recent rise in resistance to accessible immunotherapy alternatives, with some patients demonstrating innate resistance to these drugs despite past sensitisation to these agents. However, various obstacles stand in the way of this method, most notably the practicality of sequencing each patient's mutanome, selecting immunotherapy targets, and manufacturing specific medications on a large scale. With the robustness and advancement in research techniques, artificial intelligence (AI) is a potential tool that can help refine the mutanome-based immunotherapy for melanoma. Mutanome-based techniques are being employed in the development of immune-stimulating vaccines, improving current options such as adoptive cell treatment, and simplifying immunotherapy responses. Although the use of AI in these approaches is limited by data paucity, cost implications, flaws in AI inference capabilities, and the incapacity of AI to apply data to a broad population, its potential for improving immunotherapy is limitless. Thus, in-depth research on how AI might help the individualisation of immunotherapy utilising knowledge of mutanomes is critical, and this should be at the forefront of melanoma management.

Blood Transfusion Predictors in Cesarean Sections for Pregnancies With Placenta Accreta and Placenta Previa: A Monocentric Tertiary Experience.

Objective The objective of this study was to analyze the possible predictors of the need for intraoperative blood transfusion in cesarean sections for pregnancies with abnormal placentation. Methods This was a retrospective study based on data from patients' electronic medical records. A total of 44 patients who were diagnosed as placenta previa or placenta accreta who delivered through cesarean section at King Fahad University Hospital, Al-Khobar, Saudi Arabia, from June 1997 to January 2021 were included in the study. Seventeen patients received intra-operative blood transfusion. The other 27 patients did not receive any blood transfusions and served as controls. Demographic data, antepartum profiles, and obstetric history were compared between the two groups. Univariate analysis and multivariate logistic regression were used to analyze the correlations between related risk factors and the need for intraoperative blood transfusion. Results Univariate analysis (χ2 test) has shown multiple factors that correlated significantly (p<0.05) with blood transfusion requirement. These factors include the presence of placenta accreta, general anesthesia, preoperative hematocrit < 33%, preoperative hemoglobin ≤ 10 g/dL, and preterm delivery at 35-36 weeks of gestation. None of these factors showed any statistical significance in multivariate analysis (logistic regression). Conclusion General anesthesia, placenta accreta, delivery at 35-36 weeks of gestation, and pre-operative anemia are possible risk factors for blood transfusion during cesarean sections for abnormal placentation. Identifying patients at increased risk is necessary to optimize pre-operative and intraoperative management.

Anti-Toxoplasma IgG Level in Type 2 Diabetic Patients: Does It Affect Glycemic Control?

Toxoplasma gondii (T. gondii) is an important opportunistic parasite which can leads to severe complications, even death in immuno-deficient patients. Diabetes is a systemic disease; considers an important factor that increases susceptibility and risk of various infections in the host by affecting the host's immune system. The aim of the current study was to determine possible relations between toxoplasma IgG antibodies titer and the level of glycemic control and vascular complications in type 2 diabetic patients. In this case control study, serum for 122 samples was analyzed using ELISA for the presence of anti-Toxoplasma- IgG-antibodies (Abs) in both type 2 diabetic patients (62) and controls (60). A1c titer (level of diabetic control) was estimated in all diabetic cases. Full history and examination were performed after all contributors' consents. Anti-Toxoplasma IgG-Abs were detected in 56.45 % of diabetic patients and in 36.67% of the controls. Toxoplasmosis was significantly found more prevalent in diabetics associated with hypertension than controls (P=0.005). Among diabetics, patients with positive anti T. gondii IgG have significant long duration of diabetes versus those with negative anti T. gondii IgG (7.14±2.962 vs.3.26±1.583 years, respectively; P < 0.001). No relations were found between types of diabetic vascular complication, level of glycemic control based on HbA1c level and occurrence of toxoplasmosis. We concluded that despite of high prevalence of anti T. gondii IgG in diabetic patients, it has no relation to diabetic complication and glycemic control.

Male infertility problems of patients with strict sperm morphology between 5-14% may be missed with the current WHO guidelines.

OBJECTIVE: In 2010 W.H.O. changed the lower reference limit for strict sperm morphology from 15 to 4%. The change was based on 5th percentile cut points from a meta-analysis on a published series of fertile men. This study investigates if patients referred for evaluation with sperm morphologies between 5-14% have identifiable etiologies of male infertility. MATERIALS AND METHODS: I.R.B. approval was obtained to review records for patients referred to the University of Michigan Center of Reproductive Medicine between May 2012-May 2014 whom had a sperm morphology of 5-14%. Semen analysis, hormone levels, and information related to an infertility diagnosis, were recorded into a de-identified database. Patients were placed into the categories 'Varicocele', 'Hypogonadism', 'Intercourse problems', 'Anti-sperm antibodies (A.S.A.)', 'Other' or 'No diagnosis'. RESULTS: A total of 253 patients were included in the study. Of these, 96/253 (38%) had a clinical varicocele; 44/253 (17%) hypogonadism; 4/253 (2%) intercourse problems; 11/253 (4%) evidence of sperm antibodies; and 15/253 (6%) had various other problems deemed potentially contributing causes of infertility. In all, nearly 67% of the subjects were identified to have a potential contributing etiology of male infertility. Similar results were found for the men with isolated low morphology (n = 194). CONCLUSIONS: This study demonstrates that 67% of men in infertile couples, who have strict sperm morphology between 5 and 14%, are found to have a potential contributing male factor infertility diagnosis. This raises the possibility that the new lower reference value for sperm morphology may result in missed opportunities for proper infertility assessment.