The Effects of Mild Intermittent Hypoxia Exposure on the Abdominal Subcutaneous Adipose Tissue Proteome in Overweight and Obese Men: A First-in-Human Randomized, Single-Blind, and Cross-Over Study

Adipose tissue (AT) oxygen tension (pO2) has been implicated in AT dysfunction and metabolic perturbations in both rodents and humans. Compelling evidence suggests that hypoxia exposure alters metabolism, at least partly through effects on AT. However, it remains to be elucidated whether mild intermittent hypoxia (MIH) exposure impacts the AT proteome. We performed a randomized, single-blind, and cross-over study to investigate the effects of seven consecutive days of MIH (FiO2 15%, 3x2h/d) compared to normoxia (FiO2 21%) exposure on the AT proteome in overweight/obese men. In vivo AT insulin sensitivity was determined by the gold standard hyperinsulinemic-euglycemic clamp, and abdominal subcutaneous AT biopsies were collected under normoxic fasting conditions following both exposure regimens (day 8). AT proteins were isolated and quantified using liquid chromatography-mass spectrometry. After correction for blood contamination, 1,022 AT protein IDs were identified, of which 123 were differentially expressed following MIH (p < 0.05). We demonstrate for the first time that MIH exposure, which markedly reduces in vivo AT oxygen tension, impacts the human AT proteome. Although we cannot exclude that a single differentially expressed protein might be a false positive finding, several functional pathways were altered by MIH exposure, also after adjustment for multiple testing. Specifically, differentially expressed proteins were involved in redox systems, cell-adhesion, actin cytoskeleton organization, extracellular matrix composition, and energy metabolism. The MIH-induced change in AT TMOD3 expression was strongly related to altered in vivo AT insulin sensitivity, thus linking MIH-induced effects on the AT proteome to metabolic changes in overweight/obese humans.

The value of flexible endoscopy with Narrow Band Imaging for the evaluation of recurrence of laryngeal and hypopharyngeal tumours after radiotherapy

Background: The dia­gnosis of recurrent upper aerodigestive tumours is difficult, especially in the case of previous curative radiotherapy (RT) or chemoradiotherapy (CRT). Progress in the dia­gnostics of head and neck cancer came with the development of optical endoscopic imaging methods. The aim of this study was to analyse the benefits of flexible Narrow Band Imaging (NBI) in the visualization of suspected recurrence of malignancy in patients after curative RT (CRT). Methods: A total of 58 examined patients in follow-up after curative RT or CRT for laryngeal and hypopharyngeal squamous cell carcinoma were enrolled in the study. All patients underwent transnasal flexible endoscopy in conventional white light and NBI in local anaesthesia. Changes in microvascular architecture (intraepithelial papillary capillary loops – IPCL) have been classified according to Ni. IPCL I–III were considered to be non-suspicious, and therefore no histopathological examination was indicated. IV and V type findings were verified using HDTV NBI intraoperatively with bio­psy sampling and subsequent histopathological correlation was performed. Results: Transnasal videoendoscopic examination with NBI revealed a suspicious finding (IPCL type IV and V) in 23/58 (39.7%) patients, non-suspicious finding (IPCL I–III) in 35/58 (60.3%). Histopathological examination verified the positive finding (precancerous or malignant changes) in 12/23 (52.2%) and negative finding in 11/23 (47.8%) cases. The sensitivity, specificity, positive and negative predictive value of flexible NBI endoscopy were 100%, 76.1%, 52.2% and 100% respectively. According to the Kappa index (K = 0.568), we proved a moderate concordance between flexible NBI endoscopy and histopathological results. Conclusions: Transnasal flexible endoscopy with NBI in outpatient settings contributes to an early detection of pathological changes also in post-radiation altered mucosa of the larynx and hypopharynx, while a correct interpretation of in NBI findings is required to reduce the incidence of false positive results. Keywords: squamous cell carcinoma – Larynx – radiotherapy – narrow band imaging – Ni classification – hypopharynx

Association of Electrolyte Changes and Inflammatory Markers with Renal Involvement in Children with Febrile UTI

Background: We need some simpler, cheaper, and less burdensome tools to investigate the severity of renal parenchymal involvement in children with clinical pyelonephritis. Objectives: The present study was designed to investigate the relationship between electrolyte changes with renal involvement as documented by dimercaptosuccinic acid (DMSA) scan in children with febrile urinary tract infection (UTI). Methods: This is a retrospective cohort study, involving 158 children aged two months to 14 years with febrile UTI admitted to Taleghani Hospital in Gorgan from 2018 to 2019. Their documents in hospital were analyzed. They were divided into two groups with positive or negative defects on DMSA scan. Clinical and laboratory data were studied. Statistical analysis was performed using SPSS version 18. Data were analyzed using independent t-test with normal distribution of variables, otherwise chi-square test was used. The statistical significance level of the study was considered 0.05. Results: Among the 158 children, 78 patients (49.4%) had normal DMSA scan results, and 80 patients (50.6%) had an abnormal result. The mean age in month was not different between the two groups. In patients with positive renal cortical defects on DMSA Scintigraphy (group 2), ESR was significantly higher than the first group (P < 0.05). The mean serum Na level in the second group was lower than in the first group; however, it was only slightly significant (P = 0.058). The two groups showed no difference with respect to serum potassium, urine specific gravity (SG), WBC count, and the duration of fever (P > 0.05). The frequency distribution of proteinuria was not different between the two groups (P = 0.836). Conclusions: We suggest that increased ESR, positive CRP, and the presence of reflux can predict renal parenchymal involvement in children with febrile UTI as evidenced by a positive finding on DMSA scan, and the presence of hyponatremia has a little predictive value in this regard.

Validity and Reliability of the Sport Readiness Questionnaire Focused on Musculoskeletal Injuries

Background: The pre-participation physical evaluation (PPE), which includes a musculoskeletal system evaluation, identifies factors that may be a risk for athletes while practicing sport. Thus, the Sport Readiness Questionnaire, focused on musculoskeletal injuries (MIR-Q) was developed to screen athletes at risk of future injuries or worsening pre-existing injuries during training or competition. However, the criterion-related validity and reliability of the MIR-Q have not yet been analyzed. Objectives: To test the criterion-related validity and reliability (internal consistency and test-retest) of the MIR-Q. Methods: One hundred and twenty adult athletes from different sports (17 women) completed the MIR-Q and underwent a physical orthopedic examination (POE) performed by an orthopedic physician. At least one affirmative answer on the MIR-Q, as well as one positive finding on the POE, was considered “a risk factor for sport injury”. The validity was assessed from sensitivity, specificity, and accuracy measurements. Internal consistency was obtained through the KR-20 test. Reliability was measured using the test-retest method in a 7-14-day interval with a sub-sample (n = 41) and verified by the Kappa index. Results: Eighty-one (67.5%) questionnaires contained positive responses. The sensitivity of the MIR-Q against POE was high (84.4%), while specificity and accuracy were considered moderate, with values of 42.7% and 58.0%, respectively. Internal consistency was moderate (KR-20 = 0.57), and test-retest was reduced (K = 0.30; P = 0.02). Conclusions: The MIR-Q was associated with high values of validity and low values of reliability. The questionnaire may be an alternative tool for musculoskeletal screening during PPE in limited medical settings (sports OR orthopedic physician) conditions. Future studies should investigate the predictive validity of the MIR-Q, and psychometric properties of the questionnaire with younger athletes.

Comparing the clinical performance and cost efficacy of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 in the diagnosis of recurrent prostate cancer: a Markov chain decision analysis

Purpose Amongst others, [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 are available for the detection of recurrent prostate cancer (rPC). There are currently limited data comparing the performance of these two radioligands with respect to clinical outcomes or their cost efficacy, which this study aims to address. Methods Two hundred and forty-four patients undergoing PSMA PET/CT for rPC were retrospectively analysed for this study (one hundred and twenty two with each radiopharmaceutical) to generate rates of PET positivity, negativity and unclear findings. Patients underwent follow-up to determine the rate of additional examinations and to confirm PET findings. A Markov chain decision analysis was implemented to model clinical decision-making processes and to analyse clinical performance of the two tracers. We determine their clinical cost efficacies using cost data from several countries where both radiotracers are in routine use. Results The PET positivity rate was non-significantly higher for [18F]PSMA-1007 compared to [68Ga]Ga-PSMA-11 (91.8% vs. 86.9%, p = 0.68), whereas the rate of uncertain findings was significantly greater (17.2% vs. 8.25%, p = 0.02). The probability of a true positive finding was higher for [68Ga]Ga-PSMA-11 (0.90, 95% CI 0.70-0.98) vs. [18F]PSMA-1007 (0.81, 95% CI 0.66–0.91). A significantly (p < 0.0001) higher PPV for [68Ga]Ga-PSMA-11 (0.99, 95% CI 0.99–1.0 vs. 0.86) was found compared to [18F]PSMA-1007 (0.86, 95% CI 0.82–1.00). Intervention efficacy analysis favoured [68Ga]Ga-PSMA-11, where the number needed to image (to achieve a true positive finding) was 10.58 and the number needed to image to harm (to achieve a false positive finding) was − 8.08. A cost efficacy analysis favours [68Ga]Ga-PSMA-11 in three of the four jurisdictions analysed where health economic data was available (Switzerland, Israel, Australia) and [18F]PSMA-1007 in one jurisdiction (Denmark). Conclusion The analysis reveals a non-significantly higher PET positivity rate for [18F]PSMA-1007, but finds significantly greater rates of uncertain findings and false positive findings when compared to [68Ga]Ga-PSMA-11. We find differences in the two tracers in terms of clinical performance and cost efficacy. The method presented herein is generalisable and can be used with clinical or cost data for other countries or tracers.

Molecular and Biological Characterization of Transient Antithrombin Deficiency: A New Concept in Congenital Thrombophilia

Antithrombin deficiency, mainly but not exclusively due to SERPINC1 gene variants, is a major thrombophilia that is significantly associated to early-onset venous thromboembolism. The diagnostic algorithm of antithrombin deficiency relies on the classical biochemical-molecular sequence, adopted for all thrombophilic states. Therefore, genetic analysis of SERPINC1 is restricted to cases with confirmed antithrombin deficiency, that is, cases with at least two positive findings by using functional assays or with other relatives carrying this disorder. This strategy has enabled the identification of gene variants in up to 80% of cases with antithrombin deficiency and rendered plenty of both biochemical and genetic knowledge about antithrombin. Furthermore, defects of N-glycosylation underlie a proportion of cases with antithrombin deficiency that is not explained by SERPINC1 variants. Nevertheless, diagnosis of antithrombin deficiency still encloses some uncertain puzzling questions. Although the prevalence of antithrombin deficiency is tremendously low, the use of high-throughput nucleotide sequencing for genetic analysis of SERPINC1 in consecutive patients with thromboembolic events suggests that antithrombin deficiency might be and underestimated disorder that surreptitiously increases thrombotic risk. Additionally, false negative results by using functional methods for antithrombin deficiency screening have been reported, all involving type II deficiencies. The present study aimed to identify gene defects and mechanisms involved in a specific type of antithrombin deficiency that might be elusive to an easy diagnosis to the classic diagnostic strategy. We addressed this aim with an original approach, the selection of cases with at least a positive finding by functional methods that however was not confirmed by a second analysis in other laboratory or in other sample from the same patient: what we have called transient antithrombin deficiency. This work included a total of 444 consecutive unrelated subjects, referred to our centre from more than 20 European hospitals during 23 years (1998-2021), with potential antithrombin deficiency, based on at least one positive functional assay performed at the hospital of origin. At least a new sample from all patients was delivered to our centre, so a new functional assay (a uniform anti-FXa assay for all recruited samples) was carried out for validation. By performing a full clinical, biological and characterization, a genetic defect was observed in 84.6% of 305 cases with constitutive deficiency, those with consistent deficiency in all tested samples: 248 in SERPINC1 and 10 had N-glycosylation defects. These results are fully compatible with those obtained from other large cohorts, supporting the high success rate of identification of a SERPINC1 genetic variant in these patients, and confirmed the relevance of disorders of glycosylation among cases with not SERPINC1 defect. But more interestingly, our study identified a molecular basis explaining antithrombin deficiency in 43.9% of 139 cases who had normal antithrombin activity in at least one sample, what we called transient antithrombin deficiency. These 61 cases, all with thrombosis, had missense SERPINC1 mutations (N=48), with two recurrent mutations (p.Ala416Ser, antithrombin Cambridge II, N=15 and p.Val30Glu, antithrombin Dublin, N=12) or N-glycosylation defects (N=13). Two mechanisms explained transient deficiency: the limitation of current functional methods to detect some variants, and the influence of external factors (conformational stress, generation of thrombin, alcohol intake) on the pathogenic consequences of these mutations. Our study supports that antithrombin deficiency is underestimated and cases with moderate risk of thrombosis may be missed if only functional methods and classical diagnostic algorithms are used. Furthermore, although we must take into consideration that most cases with transient deficiency are explained by acquired deficiency and laboratory mistakes, this work shows new evidences supporting that the pathogenic effect of a gene defect may be modulated by external factors, changing the paradigm of congenital thrombophilia and making it also a transient disorder. Disclosures No relevant conflicts of interest to declare.

How communication can help women who experience a maternal near-miss: a qualitative study from Tanzania

ObjectivesThis study aimed to explore experiences of communication as an element of quality of care, among women surviving a maternal near-miss event, thus women who nearly died but survived haemorrhage, or pre-eclampsia complication during pregnancy, childbirth or within 42 days of termination of pregnancy.DesignA descriptive, phenomenological, qualitative study using semistructured interviews with women who survived a maternal near-miss in Southern Tanzania.SettingThe participants were recruited from two selected hospitals in Mtwara Region, where women sought child birth care and developed near-miss condition.ParticipantsParticipants for this study were women who experienced and survived a maternal near-miss event and who had lived in the study area for at least 1 year. Women were recruited using an adapted version of the WHO criteria for maternal near-miss.Data collectionWe identified 16 women and were able to conduct 10 in-depth interviews with women at their homes, 4 weeks after they were discharged. The interviews were audiorecorded and transcribed and translated word for word from Kiswahili. Thematic analysis was used to identify emerging themes.ResultsThree major themes evolved: (1) Being informed about the care and interaction, (2) Being engaged and encouraged and (3) Being afraid to ask questions. The study highlighted that good communication with women during the provision of care helped women feel grateful, supported and cared for. Women who were unconscious during care were often not informed later of what happened. This created some negative feelings and anxiety.ConclusionThis study highlights the importance of communication, and of being informed of what happened and why. Empathetic communication with sufficient explanation on what happened and why created trust among women—a positive finding which should encourage the development of consistent approaches to strengthen healthcare provider communication skills.

Emergence of Colistin Resistance against Multi-Drug Resistance Microorganisms and its Clinical Outcomes

Background: Over the past decade, excessive use of Colistin against multidrug-resistant, Gram-negative bacteria have resulted in the evolution of resistance to Colistin. Objective: To evaluate efficacy of Colistin against multidrug-resistant organisms (MDRO), the emergence of Colistin resistance and its effects on clinical outcomes. Study Design: Retrospective study Place and Duration of Study: King Saud Medical City (KSMC) from 1st October 2015 till 31st January 2016. Methodology: Forty-three patients, resistant to Colistin on blood culture and sensitivity were enrolled. Results: Colistin was not effective at breaking the MDRO. The results revealed no significant impact of Colistin on site of infection such as chest, urinary tract or skin (p=0.612), types of organisms (p=0.629), length of hospital stay and the IV Colistin days (p=0.097 and p=0.166 respectively) in the past 12 months. The positive finding was that more than two third (76.7%) of the ICU patients were alive. Conclusion: Emergence of Multi drug resistance organism is matter of global concern that caused the ineffectiveness of many potent antibiotics and led to the drastic clinical outcomes. Collaboration between medical, paramedical, and administrative staff, with strict implementation of preventive protocol can slow down the velocity of microbial multidrug resistance. Keywords: Multi-drug resistant, Colistin, Outbreak, Intensive care unit, critically ill patients

Attitudes towards natural sciences in students from mexico, colombia and peru

In science didactics the study of attitudes informs about the professional and socio-scientific profiles, for this reason this study has focused its analysis on Mexican, Colombian and Peruvian students to determine their attitudes towards the knowledge, teaching and learning of the natural Sciences. For this, a study was approached with a semantic differential scale allowing to conclude that the students have an intermediate level (between neutral and positive), finding only significant differences depending on the locality. En didáctica de las ciencias el estudio de las actitudes informa sobre los perfiles profesiones y socio-científicos, por ello este estudio ha centrado su análisis en estudiantes mexicanos, colombianos y peruanos para determinar sus actitudes hacia el conocimiento, la enseñanza y el aprendizaje de las ciencias naturales. Para ello se abordó un estudio con una escala de diferencial semántico permitiendo concluir que los estudiantes poseen un nivel intermedio (entre lo neutral y lo positivo), hallando sólo diferencias significativas en función a la localidad.

Greening of the syllabus in faculties of education sciences through sustainable development goals: the case of public Andalusian universities (Spain)

Purpose The purpose of this paper is to analyse the presence of the sustainable development goals (SDGs) proposed by the UN (2015) in university degrees within the fields of education, humanities and environmental sciences (ES) at Andalusian public institutions (Spain). Design/methodology/approach This paper shows an empirical analysis from a mixed methodological model on a total of 99 syllabi and training programs from nine different universities. The collection of information has been carried out through a rubric specifically designed within the framework of this body of research. Findings The results show that the syllabus of the subjects in the faculties of education includes the SDGs related to the social aspect of sustainability, with special focus on SDG4, SDG5, SDG10, SDG16 and SDG17, whereas others like SDG6 and SDG7 are less represented. SDGs are present in the majority of syllabus of the subjects analysed. It is certainly a positive finding which shows predisposition and a high interest on by the teachers involved. However, this is not enough as there is still a long way to go until achieving a thorough and complete incorporation of the principles of sustainability. Originality/value This research sheds light on the changes and transformations that the discourse linked to sustainability is generating in the university syllabi. Taking the SDG as a framework this paper highlights the most original aspects: a replicable methodology that allows diagnosing the level of curricular greening of the university syllabi is provided to other contexts the innovative value of connecting teaching with local and global environmental problems in their physical-chemical social and economic dimensions is shown and it has been possible to compare the difficulties of some universities in addressing compliance with the SDGs and curricular sustainability from a systemic and integrative perspective that will lead to methodological transformation and pedagogical renewal.