Stereocontrol via Propeller Chirality in FLP-Catalyzed Asymmetric Hydrogenation.

Utilization of chiral frustrated Lewis pairs as catalysts in enantioselective hydrogenation of unsaturated molecules represents a promising approach in asymmetric synthesis. In our effort to improve our current understanding of the factors governing the stereoselectivity in these catalytic processes, herein we examined the mechanism of direct hydrogenation of aromatic enamines catalyzed by a binaphthyl-based chiral amino-borane. Our computational analysis reveals that only one particular conformer of the key borohydride reaction intermediate can be regarded as a reactive form of this species. This borohydride conformer has a well-defined chiral propeller shape, which induces facial selectivity in the hydride transfer to pro-chiral iminium intermediates. The propeller chirality of the reactive borohydride conformer is generated by the axially chiral binaphthyl scaffold of the amino-borane catalyst through stabilizing π-π stacking interactions. This new computational insight can be readily used to interpret the high degree of stereoinduction observed for these reactions. We expect that the concept of chirality relay could be further exploited in catalyst design endeavors.

Initial findings using high-resolution magnetic resonance imaging for visualisation of the sural nerve and surrounding anatomy in healthy volunteers at 7 Tesla.

BACKGROUND AND AIMS: Histopathological diagnosis is the gold standard in many acquired inflammatory, infiltrative and amyloid based peripheral nerve diseases and a sensory nerve biopsy of sural or superficial peroneal nerve is favoured where a biopsy is deemed necessary. The ability to determine nerve pathology by high-resolution imaging techniques resolving anatomy and imaging characteristics might improve diagnosis and obviate the need for biopsy in some. The sural nerve is anatomically variable and occasionally adjacent vessels can be sent for analysis in error. Knowing the exact position and relationships of the nerve prior to surgery could be clinically useful and thus reliably resolving nerve position has some utility. METHODS: 7T images of eight healthy volunteers' (HV) right ankle were acquired in a pilot study using a double-echo in steady-state sequence for high-resolution anatomy images. Magnetic Transfer Ratio images were acquired of the same area. Systematic scoring of the sural, tibial and deep peroneal nerve around the surgical landmark 7 cm from the lateral malleolus was performed (number of fascicles, area in voxels and mm2, diameter and location relative to nearby vessels and muscles). RESULTS: The sural and tibial nerves were visualised in the high-resolution double-echo in steady-state (DESS) image in all HV. The deep peroneal nerve was not always visualised at level of interest. The MTR values were tightly grouped except in the sural nerve where the nerve was not visualised in two HV. The sural nerve location was found to be variable (e.g., lateral or medial to, or crossing behind, or found positioned directly posterior to the saphenous vein). INTERPRETATION: High-resolution high-field images have excellent visualisation of the sural nerve and would give surgeons prior knowledge of the position before surgery. Basic imaging characteristics of the sural nerve can be acquired, but more detailed imaging characteristics are not easily evaluable in the very small sural and further developments and specific studies are required for any diagnostic utility at 7T.

The activities of suaveolol and other compounds from Hyptis suaveolens and Momordica charantia against the aetiological agents of African trypanosomiasis, leishmaniasis and malaria.

African trypanosomiasis and malaria are among the most severe health challenges to humans and livestock in Africa and new drugs are needed. Leaves of Hyptis suaveolens Kuntze (Lamiaceae) and Momordica charantia L. (Cucurbitaceae) were extracted with hexane, ethyl acetate, and then methanol, and subjected to silica gel column chromatography. Structures of six isolated compounds were elucidated through NMR and HR-EIMS spectrometry. Callistrisic acid, dehydroabietinol, suaveolic acid, suaveolol, and a mixture of suaveolol and suaveolic acid (SSA) were obtained from H. suaveolens, while karavilagenin D and momordicin I acetate were obtained from M. charantia. The isolated biomolecules were tested against trypomastigotes of Trypanosoma brucei brucei and T. congolense, and against Plasmodium falciparum. The most promising EC50 values were obtained for the purified suaveolol fraction, at 2.71 ± 0.36 µg/mL, and SSA, exhibiting an EC50 of 1.56 ± 0.17 µg/mL against T. b. brucei trypomastigotes. Suaveolic acid had low activity against T. b. brucei but displayed moderate activity against T. congolense trypomastigotes at 11.1 ± 0.5 µg/mL. Suaveolol and SSA were also tested against T. evansi, T. equiperdum, Leishmania major and L. mexicana but the antileishmanial activity was low. Neither of the active compounds, nor the mixture of the two, displayed any cytotoxic effect on human foreskin fibroblast (HFF) cells at even the highest concentration tested, being 200 µg/mL. We conclude that suaveolol and its mixture possessed significant and selective trypanocidal activity.

Deliveries in Lebanon, the Country with the Highest Refugee Density in the World: A Descriptive Review.

PURPOSE: The aim of this study is to analyze obstetrical and reproductive health parameters in Lebanon from 2015 until 2018 in the setting of the Syrian refugee influx in order to evaluate potential risks and provide a management plan to improve outcomes. DESCRIPTION: Data from the Lebanese Ministry of Public Health (LMPH) on all obstetrical deliveries that occurred in Lebanon between 2015 and 2018 was screened and analyzed. Number and mode of delivery as well as maternal and neonatal outcomes were included. Joinpoint regression analysis was used for trends of selected parameters. Independent two-sample t-tests were used for comparisons. ASSESSMENT: Women of non-Lebanese nationality residing in Lebanon had a significantly greater number of total deliveries (p-value < 0.001), vaginal deliveries (p-value = 0.002), cesarean sections (p-value = 0.02). When looking at delivery trends from 2015 to 2018, Lebanese women had a significant decrease in total number of deliveries (p-value < 0.001) and vaginal deliveries (p-value < 0.001). CONCLUSION: Total number of deliveries and cesarean sections is on the rise in Lebanon. Cesarean section practice should be audited by the LMPH and the Lebanese Order of Physicians (LOP). Local and international agencies should prioritize the implementation and management of family planning facilities in refugee hosting countries.

Statin use and longitudinal changes in quantitative MRI-based biomarkers of thigh muscle quality: data from Osteoarthritis Initiative.

OBJECTIVE: To assess whether changes in MRI-based measures of thigh muscle quality associated with statin use in participants with and without/at-risk of knee osteoarthritis. METHODS: This retrospective cohort study used data from the Osteoarthritis Initiative study. Statin users and non-users were matched for relevant covariates using 1:1 propensity-score matching. Participants were further stratified according to baseline radiographic knee osteoarthritis status. We used a validated deep-learning method for thigh muscle MRI segmentation and calculation of muscle quality biomarkers at baseline, 2nd, and 4th visits. Mean difference and 95% confidence intervals (CI) in longitudinal 4-year measurements of muscle quality biomarkers, including cross-sectional area, intramuscular adipose tissue, contractile percent, and knee extensors and flexors maximum and specific contractile force (force/muscle area) were the outcomes of interest. RESULTS: After matching, 3772 thighs of 1910 participants were included (1886 thighs of statin-users: 1886 of non-users; age: 62 ± 9 years (average ± standard deviation), range: 45-79; female/male: 1). During 4 years, statin use was associated with a slight decrease in muscle quality, indicated by decreased knee extension maximum (mean-difference, 95% CI: - 1.85 N/year, - 3.23 to - 0.47) and specific contractile force (- 0.04 N/cm2/year, - 0.07 to - 0.01), decreased thigh muscle contractile percent (- 0.03%/year, - 0.06 to - 0.01), and increased thigh intramuscular adipose tissue (3.06 mm2/year, 0.53 to 5.59). Stratified analyses showed decreased muscle quality only in participants without/at-risk of knee osteoarthritis but not those with established knee osteoarthritis. CONCLUSIONS: Statin use is associated with a slight decrease in MRI-based measures of thigh muscle quality over 4 years. However, considering statins' substantial cardiovascular benefits, these slight muscle changes may be relatively less important in overall patient care.

CT-derived pectoralis composition and incident pneumonia hospitalization using fully automated deep-learning algorithm: multi-ethnic study of atherosclerosis.

BACKGROUND: Pneumonia-related hospitalization may be associated with advanced skeletal muscle loss due to aging (i.e., sarcopenia) or chronic illnesses (i.e., cachexia). Early detection of muscle loss may now be feasible using deep-learning algorithms applied on conventional chest CT. OBJECTIVES: To implement a fully automated deep-learning algorithm for pectoralis muscle measures from conventional chest CT and investigate longitudinal associations between these measures and incident pneumonia hospitalization according to Chronic Obstructive Pulmonary Disease (COPD) status. MATERIALS AND METHODS: This analysis from the Multi-Ethnic Study of Atherosclerosis included participants with available chest CT examinations between 2010 and 2012. We implemented pectoralis muscle composition measures from a fully automated deep-learning algorithm (Mask R-CNN, built on the Faster Region Proposal Network (R-) Convolutional Neural Network (CNN) with an extension for mask identification) for two-dimensional segmentation. Associations between CT-derived measures and incident pneumonia hospitalizations were evaluated using Cox proportional hazards models adjusted for multiple confounders which include but are not limited to age, sex, race, smoking, BMI, physical activity, and forced-expiratory-volume-at-1 s-to-functional-vital-capacity ratio. Stratification analyses were conducted based on baseline COPD status. RESULTS: This study included 2595 participants (51% female; median age: 68 (IQR: 61, 76)) CT examinations for whom we implemented deep learning-derived measures for longitudinal analyses. Eighty-six incident pneumonia hospitalizations occurred during a median 6.67-year follow-up. Overall, pectoralis muscle composition measures did not predict incident pneumonia. However, in fully-adjusted models, only among participants with COPD (N = 507), CT measures like extramyocellular fat index (hazard ratio: 1.98, 95% CI: 1.22, 3.21, p value: 0.02), were independently associated with incident pneumonia. CONCLUSION: Reliable deep learning-derived pectoralis muscle measures could predict incident pneumonia hospitalization only among participants with known COPD. CLINICAL RELEVANCE STATEMENT: Pectoralis muscle measures obtainable at zero additional cost or radiation exposure from any chest CT may have independent predictive value for clinical outcomes in chronic obstructive pulmonary disease patients. KEY POINTS: •Identification of independent and modifiable risk factors of pneumonia can have important clinical impact on patients with chronic obstructive pulmonary disease. •Opportunistic CT measures of adipose tissue within pectoralis muscles using deep-learning algorithms can be quickly obtainable at zero additional cost or radiation exposure. •Deep learning-derived pectoralis muscle measurements of intermuscular fat and its subcomponents are independently associated with subsequent incident pneumonia hospitalization.

Pediatric community acquired urinary tract infections due to extended-spectrum beta-lactamase versus non-extended-spectrum beta-lactamase producing bacteria.

BACKGROUND: This study aimed to evaluate the demographics, clinical characteristics, risk factors, and antibiotic resistance of pediatric community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL-producing uropathogens. METHODS: This retrospective study was conducted at a tertiary care hospital in Saudi Arabia, among children aged between 0 and 14 years, with a culture-proven diagnosis of community-acquired UTI between February 2019 and September 2021. Patients were divided into two groups based on whether or not their UTI was caused by ESBL-producing bacteria. RESULTS: A total of 383 patients with community-acquired UTI were evaluated. Escherichia coli was detected in 72.6% of cultures. Extended-spectrum beta-lactamase-producing organisms were responsible for 35.7% of UTI episodes. Of these 69% and 31% were caused by E. coli and Klebsiella pneumoniae, respectively. There were no significant differences between the two groups with regard to clinical presentation or urine analysis. The resistance rates in the ESBL-producing group were 39.4% for amoxicillin/clavulanic acid, 65.7% for ciprofloxacin, 72.3% for co-trimoxazole, 32.8% for nitrofurantoin, 21.2% for gentamicin, and 0.7% for amikacin and carbapenems. In the non-ESBL-producing group, it was 22.4% for amoxicillin/clavulanic acid, 22.4% for ciprofloxacin, 38.2% for co-trimoxazole, 23.6% for nitrofurantoin, 6.1% for gentamicin, and zero for amikacin and carbapenems. The presence of renal abnormalities (p = 0.014) and male gender (p = 0.026) were determined to be independent risk factors for ESBL UTIs. CONCLUSIONS: Recognizing risk factors and antibiotic resistance for ESBL-producing bacteria may aid in tailoring an antibiotic regimen for pediatric patients at high risk of ESBL-UTIs.

Genomic signatures for drylands adaptation at gene-rich regions in African zebu cattle.

BACKGROUND: Indigenous Sudanese cattle are mainly indicine/zebu (humped) type. They thrive in the harshest dryland environments characterised by high temperatures, long seasonal dry periods, nutritional shortages, and vector disease challenges. Here, we sequenced 60 indigenous Sudanese cattle from six indigenous breeds and analysed the data using three genomic scan approaches to unravel cattle adaptation to the African dryland region. RESULTS: We identified a set of gene-rich selective sweep regions, detected mostly on chromosomes 5, 7 and 19, shared across African and Gir zebu. These include genes involved in immune response, body size and conformation, and heat stress response. We also identified selective sweep regions unique to Sudanese zebu. Of these, a 250 kb selective sweep on chromosome 16 spans seven genes, including PLCH2, PEX10, PRKCZ, and SKI, which are involved in alternative adaptive metabolic strategies of insulin signalling, glucose homeostasis, and fat metabolism. CONCLUSIONS: Our results suggest that environmental adaptation may involve recent and ancient selection at gene-rich regions, which might be under a common regulatory genetic control, in zebu cattle.

Accuracy of Whole Blood Cardiac Troponin I in the Diagnosis of Childhood Heart Failure at the University College Hospital, Ibadan.

OBJECTIVE: To determine the accuracy of cardiac troponin I (cTnI), a marker of myocardial cell injury or necrosis, in correctly identifying heart failure in children. PATIENTS, MATERIALS, AND METHODS: This was a crosssectional study in which 45 children aged 12 years or below admitted into the paediatric wards of the University College Hospital, Ibadan, who, on evaluation with the Ibadan Childhood Heart Failure Index (ICHFI) had a score of ≥ 3, were consecutively recruited. Forty-five age- and sex-matched apparently healthy children with ICHFI score of <3 were similarly evaluated as controls. Demographic, clinical data and cTnI values were documented. Statistical analysis was done using IBM SPSS version 23. RESULTS: There was a strong positive correlation (0.592) between the whole blood cTnI values and ICHFI scores (rs = 0.592, P = 0.000). At a cut-off value of 0.07ng/ml, the whole blood cTnI had a sensitivity of 26.7%, specificity of 97.8%, a positive predictive value of 92.8% and a negative predictive value of 57.1%. The receiver operating characteristic curve plotted had an AUC of 0.800 at the 95% CI, 0.704 - 0.896; P < 0.001. CONCLUSION: Whole blood cTnI level is elevated in children in heart failure and may predict severity of the condition. Whole blood cTnI was found to be an accurate tool for the exclusion of heart failure in children and is therefore recommended for use in children with suspected heart failure for its rapid diagnosis.

OBJECTIF: Déterminer la précision de la troponine cardiaque I (cTnI), un marqueur de lésion ou de nécrose des cellules myocardiques, dans l'identification correcte de l'insuffisance cardiaque chez les enfants. PATIENTS, MATÉRIEL ET MÉTHODE: Il s'agit d'une étude transversale dans laquelle 45 enfants âgés de 12 ans ou moins admis dans les services pédiatriques de University College Hospital, Ibadan, qui, après évaluation avec Ibadan Childhood Heart Failure Index (ICHFI), avaient un score ≥ 3, ont été recrutés consécutivement. Quarante-cinq enfants apparemment sains, appariés selon l'âge et le sexe, avec un score ICHFI de <3 ont été évalués de la même manière en tant que témoins. Les données démographiques, cliniques et les valeurs de cTnI ont été documentées. L'analyse statistique a été réalisée à l'aide d'IBM SPSS version 23. RÉSULTATS: Il existe une forte corrélation positive (0,592) entre les valeurs de cTnI dans le sang total et les scores ICHFI (rs = 0,592, P = 0,000). À une valeur seuil de 0,07 ng/ml, le cTnI du sang total avait une sensibilité de 26,7 %, une spécificité de 97,8 %, une valeur prédictive positive de 92,8 % et une valeur prédictive négative de 57,1 %. La courbe caractéristique du récepteur tracée avait une AUC de 0,800 à l'IC de 95 %, 0,704 - 0,896 ; P < 0,001. CONCLUSION: Le taux de cTnI dans le sang total est élevé chez les enfants souffrant d'insuffisance cardiaque et peut prédire la gravité de la maladie. Le taux de cTnI dans le sang total s'est avéré être un outil précis pour l'exclusion de l'insuffisance cardiaque chez les enfants et il est donc recommandé de l'utiliser chez les enfants suspectés d'insuffisance cardiaque pour un diagnostic rapide de l'insuffisance cardiaque. Mots clés: Troponine cardiaque I, Insuffisance cardiaque chez l'Enfant, Ibadan.

Stroke in Middle Eastern children with cancer: prevalence and risk factors.

OBJECTIVE: To determine the prevalence and to characterize the different types of strokes in children with cancer at the Children's Cancer Center of Lebanon (CCCL), in addition to assess the factors and clinical findings leading to stroke in children. METHODS: We retrospectively reviewed the medical records and brain images (MRIs and CTs) of children admitted to the CCCL and diagnosed with cancer between years 2008 and 2017. Brain images were reviewed for the strokes' onset, size, location, possible origin, its recurrence and type: intracranial hemorrhage (ICH), acute arterial ischemic stroke, and cerebral sinus venous thrombosis (CSVT) with and without venous infarct. Medical charts of the patients were reviewed for age, sex, their type of cancer, the treatment protocol they followed, and abnormal findings on their laboratory studies and neurological exams. RESULTS: Out of the 905 charts reviewed, twenty-seven children with variable types of cancer had strokes, with a prevalence of 2.9%. Their median age at cancer diagnosis was 9.4 (4.8-13.7) years and the median age at stroke onset was 10.6 (6.7-15.5) years. The median time between the cancer diagnosis and the stroke episode was 6 months. CSVT cases were the most common (60%) followed by acute arterial ischemic (22%) and hemorrhagic strokes (18%), with CSVT being the latest to occur. We observed that the different types of strokes were related to some types of cancer. Of the children that had acute arterial ischemic stroke in this cohort, 83% had brain tumors, of the children who had CSVT, 87.5% had leukemia, and of the children who had hemorrhagic stroke, 40% had leukemia. Neurological abnormalities were more prevalent in acute arterial ischemic stroke (80%). Patients with CSVT recovered better than those with other types of strokes. Strokes recurred in 60% of ischemic strokes. L-Asparaginase was significantly associated with CSVT. CONCLUSIONS: The prevalence of strokes was 2.9% in children with cancer. We were able to identify factors related to the types of the stroke that occurred in children including the type and location of the cancer the type of treatment received, and stroke recurrence.

A Toxoplasma gondii Oxopurine Transporter Binds Nucleobases and Nucleosides Using Different Binding Modes.

Toxoplasma gondii is unable to synthesize purines de novo, instead salvages them from its environment, inside the host cell, for which they need high affinity carriers. Here, we report the expression of a T. gondii Equilibrative Nucleoside Transporter, Tg244440, in a Trypanosoma brucei strain from which nucleobase transporters have been deleted. Tg244440 transported hypoxanthine and guanine with similar affinity (Km ~1 µM), while inosine and guanosine displayed Ki values of 4.05 and 3.30 µM, respectively. Low affinity was observed for adenosine, adenine, and pyrimidines, classifying Tg244440 as a high affinity oxopurine transporter. Purine analogues were used to probe the substrate-transporter binding interactions, culminating in quantitative models showing different binding modes for oxopurine bases, oxopurine nucleosides, and adenosine. Hypoxanthine and guanine interacted through protonated N1 and N9, and through unprotonated N3 and N7 of the purine ring, whereas inosine and guanosine mostly employed the ribose hydroxy groups for binding, in addition to N1H of the nucleobase. Conversely, the ribose moiety of adenosine barely made any contribution to binding. Tg244440 is the first gene identified to encode a high affinity oxopurine transporter in T. gondii and, to the best of our knowledge, the first purine transporter to employ different binding modes for nucleosides and nucleobases.

Nucleoside Transport and Nucleobase Uptake Null Mutants in Leishmania mexicana for the Routine Expression and Characterization of Purine and Pyrimidine Transporters.

The study of transporters is highly challenging, as they cannot be isolated or studied in suspension, requiring a cellular or vesicular system, and, when mediated by more than one carrier, difficult to interpret. Nucleoside analogues are important drug candidates, and all protozoan pathogens express multiple equilibrative nucleoside transporter (ENT) genes. We have therefore developed a system for the routine expression of nucleoside transporters, using CRISPR/cas9 to delete both copies of all three nucleoside transporters from Leishmania mexicana (ΔNT1.1/1.2/2 (SUPKO)). SUPKO grew at the same rate as the parental strain and displayed no apparent deficiencies, owing to the cells' ability to synthesize pyrimidines, and the expression of the LmexNT3 purine nucleobase transporter. Nucleoside transport was barely measurable in SUPKO, but reintroduction of L. mexicana NT1.1, NT1.2, and NT2 restored uptake. Thus, SUPKO provides an ideal null background for the expression and characterization of single ENT transporter genes in isolation. Similarly, an LmexNT3-KO strain provides a null background for transport of purine nucleobases and was used for the functional characterization of T. cruzi NB2, which was determined to be adenine-specific. A 5-fluorouracil-resistant strain (Lmex5FURes) displayed null transport for uracil and 5FU, and was used to express the Aspergillus nidulans uracil transporter FurD.

The Trypanosoma cruzi TcrNT2 Nucleoside Transporter Is a Conduit for the Uptake of 5-F-2'-Deoxyuridine and Tubercidin Analogues.

Among the scarce validated drug targets against Chagas disease (CD), caused by Trypanosoma cruzi, the parasite's nucleoside salvage system has recently attracted considerable attention. Although the trypanocidal activity of tubercidin (7-deazapurine) has long been known, the identification of a class of 7-substituted tubercidin analogs with potent in vitro and in vivo activity and much-enhanced selectivity has made nucleoside analogs among the most promising lead compounds against CD. Here, we investigate the recently identified TcrNT2 nucleoside transporter and its potential role in antimetabolite chemotherapy. TcrNT2, expressed in a Leishmania mexicana cell line lacking the NT1 nucleoside transporter locus, displayed very high selectivity and affinity for thymidine with a Km of 0.26 ± 0.05 µM. The selectivity was explained by interactions of 2-oxo, 4-oxo, 5-Me, 3'-hydroxy and 5'-hydroxy with the transporter binding pocket, whereas a hydroxy group at the 2' position was deleterious to binding. This made 5-halogenated 2'-deoxyuridine analogues good substrates but 5-F-2'-deoxyuridine displayed disappointing activity against T. cruzi trypomastigotes. By comparing the EC50 values of tubercidin and its 7-substituted analogues against L. mexicana Cas9, Cas9ΔNT1 and Cas9ΔNT1+TcrNT2 it was shown that TcrNT2 can take up tubercidin and, at a minimum, a subset of the analogs.

Sever's Disease of the Pediatric Population: Clinical, Pathologic, and Therapeutic Considerations.

Sever's disease is an underreported prevalent pediatric condition that causes heel pain in children worldwide. It is often described as an overuse injury that can present with either unilateral or bilateral heel pain. Even though the exact mechanism of injury is unknown, it is often thought it involves repetitive stress and pressure on the calcaneal growth plate. Diagnosing Sever's disease mainly relies on a thorough clinical investigation and physical examination, with a positive squeeze test usually sufficient to establish diagnosis. Nevertheless, radiographic imaging can help exclude other differential diagnoses. Therapeutic options of Sever's disease are mostly conservative, and these include rest, physical therapy, kinesiotherapy, and orthoses. Educating parents and coaches on the symptomatology and presentation of Sever's disease is pivotal for the establishment of efficient preventive interventions and earlier diagnoses. This study presents a case of a pediatric patient with Sever's disease and offers medical insight into the diagnostic, clinical, pathologic, and therapeutic characteristics of this condition, in light of the current existing literature.

Intraoperative and postoperative complications of gynecological laparoscopic interventions: incidence and risk factors.

PURPOSE: The aims of this study were to determine the incidence of intraoperative and postoperative complications of laparoscopic gynecological interventions and to identify risk factors for such complications. METHODS: All patients who underwent laparoscopic interventions from September 2013 to September 2017 at the Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Hospital were identified retrospectively using a prospectively compiled clinical database. Binary logistic regression analysis was used to identify independent risk factors for intra- and postoperative complications. RESULTS: Data from 3351 patients were included in the final analysis. Overall, 188 (5.6%) intraoperative and 219 (6.5%) postoperative complications were detected. On multivariate analysis, age [odds ratio (OR), 1.03; 95% confidence interval (CI) 1.01-1.04], surgery duration (OR, 1.02; 95% CI 1.02-1.03), carbon dioxide use (OR, 0.99; 95% CI 0.99-1.00), and surgical indication (all p ≤ 0.01) were independent risk factors for intraoperative and duration of surgery (OR, 1.01; 95% CI 1.01-1.02; p ≤ 0.01), carbon dioxide use (OR, 0.99; 95% CI 0.99-1.00; p ≤ 0.01), hemoglobin drop (OR, 1.41; 95% CI 1.21-1.65; p ≤ 0.01), and ASA status (p = 0.04) for postoperative complications. CONCLUSION: In this large retrospective analysis with a generally low incidence of complications (5.6% intraoperative and 6.5% postoperative complications), a representative risk collective was identified: Patients aged > 38 years, surgery duration > 99 min, benign or malignant adnex findings were at higher risk for intraoperative and patients with surgery duration > 94 min, hemoglobin drop > 2 g/dl and ASA status III at higher risk for postoperative complications.

Teaching breast ultrasound skills including core-needle biopsies on a phantom enhances undergraduate student's knowledge and learning satisfaction.

PURPOSE: To investigate whether a training program on breast ultrasound skills including core-needle biopsies to undergraduate students can improve medical knowledge and learning satisfaction. METHODS: Medical students attending mandatory classes at the Medical School of the University of Saarland received a supplemental theoretical and hands-on training program on ultrasound (US) breast screening and on US-guided core-needle biopsy using an agar-agar phantom. Experienced breast specialists and ultrasound examiners served as trainers applying Peyton's 4-step training approach. The students' theoretical knowledge and hands-on skills were tested before and after the training program, using a multiple-choice questionnaire (MCQ), the Objective Structured Clinical Examination (OSCE) and a student curriculum evaluation. RESULTS: The MCQ results showed a significant increase of the student's theoretical knowledge (50.2-75.2%, p < 0.001). After the course, the OSCE showed a mean total of 17.3/20 points (86.5%), confirming the practical implementation of the new skills. The student curriculum evaluation in general was very positive. A total of 16/20 questions were rated between 1.2 and 1.7 (very good) and 3 questions were rated as 2.1 (good). CONCLUSION: Undergraduate student's medical education can be enhanced by teaching breast US skills.

Molecular Action of Polyphenols in Leukaemia and Their Therapeutic Potential.

Leukaemia is a malignant disease of the blood. Current treatments for leukaemia are associated with serious side-effects. Plant-derived polyphenols have been identified as potent anti-cancer agents and have been shown to work synergistically with standard chemotherapy agents in leukaemia cell lines. Polyphenols have multiple mechanisms of action and have been reported to decrease cell proliferation, arrest cell cycle and induce apoptosis via the activation of caspase (3, 8 and 9); the loss of mitochondrial membrane potential and the release of cytochrome c. Polyphenols have been shown to suppress activation of transcription factors, including NF-kB and STAT3. Furthermore, polyphenols have pro-oxidant properties, with increasing evidence that polyphenols inhibit the antioxidant activity of glutathione, causing oxidative DNA damage. Polyphenols also induce autophagy-driven cancer cell death and regulate multidrug resistance proteins, and thus may be able to reverse resistance to chemotherapy agents. This review examines the molecular mechanism of action of polyphenols and discusses their potential therapeutic targets. Here, we discuss the pharmacological properties of polyphenols, including their anti-inflammatory, antioxidant, anti-proliferative, and anti-tumour activities, and suggest that polyphenols are potent natural agents that can be useful therapeutically; and discuss why data on bioavailability, toxicity and metabolism are essential to evaluate their clinical use.

Role of the Renin-Angiotensin-Aldosterone and Kinin-Kallikrein Systems in the Cardiovascular Complications of COVID-19 and Long COVID.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. Patients may present as asymptomatic or demonstrate mild to severe and life-threatening symptoms. Although COVID-19 has a respiratory focus, there are major cardiovascular complications (CVCs) associated with infection. The reported CVCs include myocarditis, heart failure, arrhythmias, thromboembolism and blood pressure abnormalities. These occur, in part, because of dysregulation of the Renin-Angiotensin-Aldosterone System (RAAS) and Kinin-Kallikrein System (KKS). A major route by which SARS-CoV-2 gains cellular entry is via the docking of the viral spike (S) protein to the membrane-bound angiotensin converting enzyme 2 (ACE2). The roles of ACE2 within the cardiovascular and immune systems are vital to ensure homeostasis. The key routes for the development of CVCs and the recently described long COVID have been hypothesised as the direct consequences of the viral S protein/ACE2 axis, downregulation of ACE2 and the resulting damage inflicted by the immune response. Here, we review the impact of COVID-19 on the cardiovascular system, the mechanisms by which dysregulation of the RAAS and KKS can occur following virus infection and the future implications for pharmacological therapies.

Concomitant Aspirin and Anticoagulation Is Associated With Increased Risk for Major Bleeding in Surgical Patients Requiring Postoperative Intensive Care.

OBJECTIVES: Critically ill surgical patients may receive concomitant aspirin and therapeutic anticoagulation postoperatively, yet the safety of this practice remains unknown. We evaluated the risk of major bleeding with concomitant therapy compared with anticoagulation alone. DESIGN: Observational cohort study. Inverse probability of treatment weighting was used to assess the association between concomitant therapy and a primary outcome of major bleeding. SETTING: Postoperative ICUs at an academic medical center. PATIENTS: Adults (≥ 18 yr old) receiving anticoagulation during postoperative ICU admission between 2007 and 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nine thousand five hundred eighteen anticoagulated patients were included, including 3,237 (34%) receiving aspirin. A total of 1,874 unique patients (19.7%) experienced a major bleeding event. In inverse probability of treatment weighting analyses, concomitant therapy was associated with increased odds for major bleeding (odds ratio, 1.20; 95% CI, 1.05-1.36; p = 0.006) compared with anticoagulation alone. An interaction test suggested a differential relationship between aspirin use and major bleeding based on aspirin use in the 7 days prior to anticoagulation, such that a strong association between aspirin and major bleeding was observed for recent initiators of aspirin (1.40; 1.13-1.72;p = 0.002) but not for those continuing prior aspirin use. Aspirin use prior to anticoagulation did not modify the relationship between concomitant therapy and new myocardial infarction or stroke (i.e., rates were not increased with aspirin discontinuation prior to anticoagulation). CONCLUSIONS: Concomitant aspirin and anticoagulation in critically ill surgical patients was associated with an increased rate of major bleeding. Future investigations are warranted to further define optimal management of antiplatelet therapy during anticoagulation in surgical patients.

Influx of diverse, drug resistant and transmissible Plasmodium falciparum into a malaria-free setting in Qatar.

BACKGROUND: Successful control programs have impeded local malaria transmission in almost all Gulf Cooperation Council (GCC) countries: Qatar, Bahrain, Kuwait, Oman, the United Arab Emirates (UAE) and Saudi Arabia. Nevertheless, a prodigious influx of imported malaria via migrant workers sustains the threat of local transmission. Here we examine the origin of imported malaria in Qatar, assess genetic diversity and the prevalence of drug resistance genes in imported Plasmodium falciparum, and finally, address the potential for the reintroduction of local transmission. METHODS: This study examined imported malaria cases reported in Qatar, between 2013 and 2016. We focused on P. falciparum infections and estimated both total parasite and gametocyte density, using qPCR and qRT-PCR, respectively. We also examined ten neutral microsatellites and four genes associated with drug resistance, Pfmrp1, Pfcrt, Pfmdr1, and Pfkelch13, to assess the genetic diversity of imported P. falciparum strains, and the potential for propagating drug resistance genotypes respectively. RESULTS: The majority of imported malaria cases were P. vivax, while P. falciparum and mixed species infections (P. falciparum / P. vivax) were less frequent. The primary origin of P. vivax infection was the Indian subcontinent, while P. falciparum was mostly presented by African expatriates. Imported P. falciparum strains were highly diverse, carrying multiple genotypes, and infections also presented with early- and late-stage gametocytes. We observed a high prevalence of mutations implicated in drug resistance among these strains, including novel SNPs in Pfkelch13. CONCLUSIONS: The influx of genetically diverse P. falciparum, with multiple drug resistance markers and a high capacity for gametocyte production, represents a threat for the reestablishment of drug-resistant malaria into GCC countries. This scenario highlights the impact of mass international migration on the reintroduction of malaria to areas with absent or limited local transmission.