Polymorphisms and circulating levels in the insulin-like growth factor system and risk of breast cancer: a systematic review.

We reviewed all English-language articles on associations among circulating levels of the insulin-like growth factors (IGF) and their binding proteins (IGFBP), polymorphisms in their genes, and breast cancer risk. In premenopausal women, five of eight IGF-I studies and four of six IGFBP-3 studies of circulating levels found that women in the highest quantile had more than twice the risk of developing breast cancer of those in the lowest, although in some this effect was only apparent at young ages. In postmenopausal women, however, there was no consistent effect. A simple sequence length polymorphism 1 kb 5' to IGF-I was examined in relation to circulating levels of IGF-I (12 studies) or breast cancer risk (4 studies), but there was no convincing evidence of any effect. For an A/C polymorphism 5' to IGFBP-3, all three studies were consistent with a modest effect on circulating levels, but no evidence of a direct effect on breast cancer risk was seen in the only relevant study. Variation within the reference range of IGF-I and IGFBP-3 may confer only modest increases in breast cancer risk, and any single polymorphism may only account for a small proportion of that variation. Nevertheless, population attributable fractions for high circulating levels of IGF-I and IGFBP-3 and for common genetic variants could be substantial. Further large studies, or combined analysis of data from existing studies, are needed to quantify these effects more precisely.     

Psychosocial effect of mastectomy versus conservative surgery in patients with early breast cancer

Purpose To compare the quality-of-life (QoL) and psycho-social changes in a group of patients with early breast cancer who underwent conservative surgery (BCS) or modified radical mastectomy (MRM). Methods Self-administered questionnaire assessing body image perception, social habits, sexual attraction and self-consciousness with relatives/friends, was randomly assigned to 125 patients (61 BCS, 64 MRM; aged 53±8 and 50±9 years, respectively, p=NS). Results MRM patients reported a significantly higher frequency of changes in body image perception and other related social behaviour such as avoiding going to the beach or using low-cut clothes, and reticence with friends. Conversely, no differences were found regarding sexuality, denial of the disease by the husband/partner, or concealing the disease from family members. Also, no significant differences were found between patients above and below the age of 50 years, for all variables studied after adjustment for surgical procedure. Conclusions Modified radical mastectomy has a negative effect on body image perception and in social behaviour patterns of patients and with a concomitant decrease in QoL. The sexuality of the patient is not significantly affected.     

A Novice Teacher as Facilitator of Learning During a Hybrid Sport Education/Step-Game Approach Volleyball Season

This study aimed to examine how a novice Physical Education teacher unfolded her pedagogical practice as a facilitator of learning during a hybrid Sport Education/Step-Game-Approach volleyball season; and to investigate students’ perceptions about their lived learning experiences and active involvement in building their own learning process. For this purpose, an insider action-research design was implemented throughout one school term (20 lessons of 45 minutes each in total). Twenty-five students (aged between16 and17 years old), enrolled in the 12^th grade at a Portuguese high school took part in this investigation. The novice teacher, who held two years of professional experience, assumed the dual role of teacher-researcher, facilitating an in-depth understanding of the complexity featuring of the teaching-learning process. Qualitative data were collected using multiple data sources (i.e., teacher’s lesson plans and field diary, and student’s focus-group interviews), and analyzed using a hybrid approach of inductive and deductive thematic analysis. The results revealed that the use of this hybrid season helped the teacher to act as facilitator of learning, namely by: (i) using two student-centered models with unique internal structures and functionalities, (ii) increasing the level of responsibility taken by students for their own learning experiences, (iii) adapting the lesson plans to students’ individual needs, and (iv) combining a more supportive intervention with the use of more indirect teaching strategies. Together, these strategies seemed to prompt students’ autonomy and sense of active control of the class activities, the development of students’ abilities and volleyball-based knowledge, leading them to be more interested and engaged in Physical Education. In conclusion, the alliance between the student-centered environment (Sport Education) and the specificity of the content subject-knowledge (Step-Game Approach for non-invasion games) seems to have allow the novice teacher to adjust her pedagogical intervention as facilitator of learning to students’ individual learning needs. Key points

• The alliance between the Sport Education and the Step-Game Approach allows the novice teacher to adjust her pedagogical intervention as facilitator of learning to students’ individual learning needs.
• Students perceived that they developed their autonomy and sense of active control of the class activities, their abilities and volleyball-based knowledge, which made them more interested and engaged in PE.
• Future studies should consider longitudinal AR designs and video-audio as a complementary data source data.
• PETE and professional development programs should be more focused on developing teacher’s ability to game design, to use effective questioning and gradually to empower students to assume an active role over their learning experiences. Also, offer school placement training and postgraduate professional practice based on student-centered approaches.

Key words: Student-centered models, volleyball, physical education, high school, action-research, qualitative analysis     

Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia

In chronic kidney disease, systemic inflammation and high serum phosphate (P) promote the de-differentiation of vascular smooth muscle cells (VSMC) to osteoblast-like cells, increasing the propensity for medial calcification and cardiovascular mortality. Vascular microRNA-145 (miR-145) content is essential to maintain VSMC contractile phenotype. Because vitamin D induces aortic miR-145, uremia and high serum P reduce it and miR-145 directly targets osteogenic osterix in osteoblasts, this study evaluated a potential causal link between vascular miR-145 reductions and osterix-driven osteogenic differentiation and its counter-regulation by vitamin D. Studies in aortic rings from normal rats and in the rat aortic VSMC line A7r5 exposed to calcifying conditions corroborated that miR-145 reductions were associated with decreases in contractile markers and increases in osteogenic differentiation and calcium (Ca) deposition. Furthermore, miR-145 silencing enhanced Ca deposition in A7r5 cells exposed to calcifying conditions, while miR-145 overexpression attenuated it, partly through increasing α-actin levels and reducing osterix-driven osteogenic differentiation. In mice, 14 weeks after the induction of renal mass reduction, both aortic miR-145 and α-actin mRNA decreased by 80% without significant elevations in osterix or Ca deposition. Vitamin D treatment from week 8 to 14 fully prevented the reductions in aortic miR-145 and attenuated by 50% the decreases in α-actin, despite uremia-induced hyperphosphatemia. In conclusion, vitamin D was able to prevent the reductions in aortic miR-145 and α-actin content induced by uremia, reducing the alterations in vascular contractility and osteogenic differentiation despite hyperphosphatemia.     

Pronóstico perinatal y materno de la gestación múltiple en función del protocolo intraparto

Objectives

To evaluate maternal and fetal outcomes of multiple pregnancy according to route of delivery.

Material and methods

We performed a retrospective study of all twin deliveries in the previous 5 years and evaluated the route of delivery, especially in the final year. The information was recorded with Microsoft EXCEL and was analyzed with the statistical program SPSS 12.0 for Windows.

Results

The mean gestational age was 35.3 weeks. Route of delivery was through cesarean section in 59.8%. The mean interval between twins was 7.82 minutes when the first twin was delivered vaginally. Neonatal morbidity was found in 49%, and was higher in the second twin and in preterm deliveries.

Conclusions

Multiple pregnancies are associated with a large number of maternal and perinatal complications, as well as with a greater number of cesarean sections. Consequently, correct intrapartum management is required to reduce neonatal morbility as far as possible.     

High intrapatient variability of tacrolimus exposure associated with poorer outcomes in liver transplantation

Tacrolimus (TAC) is a dose‐dependent immunosuppressor with considerable intrapatient variability (IPV) in its pharmacokinetics. The aim of this work is to ascertain the association between TAC IPV at 6 months after liver transplantation (LT) and patient outcome. This single‐center cohort study retrospectively analyzed adult patients who underwent transplantation from 2015 to 2019 who survived the first 6 months with a functioning graft. The primary end point was the patient’s probability of death and the secondary outcome was the loss of renal function between month 6 and the last follow‐up. TAC IPV was estimated by calculating the coefficient of variation (CV) of the dose‐corrected concentration (C₀/D) between the third and sixth months post‐LT. Of the 140 patients who underwent LT included in the study, the low‐variability group (C₀/D CV < 27%) comprised 105 patients and the high‐variability group (C₀/D CV ≥ 27%) 35 patients. One‐, 3‐, and 5‐year patient survival rates were 100%, 82%, and 72% in the high‐variability group versus 100%, 97%, and 93% in the low‐variability group, respectively (p = 0.005). Moreover, significant impaired renal function was observed in the high‐variability group at 1 year (69 ± 16 ml/min/1.73 m² vs. 78 ± 16 ml/min/1.73 m², p = 0.004) and at 2 years post‐LT (69 ± 17 ml/min/1.73 m² vs. 77 ± 15 ml/min/1.73 m², p = 0.03). High C₀/D CV 3–6 months remained independently associated with worse survival (hazard ratio = 3.57, 95% CI = 1.32–9.67, p = 0.012) and loss of renal function (odds ratio = 3.47, 95% CI = 1.30–9.20, p = 0.01). Therefore, high IPV between the third and sixth months appears to be an early and independent predictor of patients with poorer liver transplant outcomes.

Abbreviations

BPAR

Biopsy proven acute rejection

BMI

Body mass index

CKD‐EPI

chronic kidney disease epidemiology collaboration

CV

coefficient of variation

C₀/D

dose‐corrected concentration

CMV

cytomegalovirus

eGFR

estimated glomerular filtration rate

HR

hazard ratio

HCC

hepatocellular carcinoma

ICU

intensive care unit

IPV

intrapatient variability

i.v.

intravenously

LC–MS/MS

liquid chromatography‐ tandem mass spectrometry

LT

liver transplantation

MELD

model for end‐stage liver disease

MMF

mycophenolate mofetil

NASH

Non‐Alcoholic Steatohepatitis

OR

odds ratio

PCR

polymerase chain reaction

SD

Standard Deviation

TAC

tacrolimus

3–6 M

three–six months

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

There is high intrapatient variability of tacrolimus and its correlation with liver transplantation (LT) outcomes.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Could the intrapatient variability of tacrolimus between months 3 and 6 post‐LT be a potential prognostic tool for poor outcomes?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Those patients with dose‐corrected concentration coefficient of variation greater than or equal to 27% between months 3 and 6 post‐LT have worst overall survival and impaired renal function.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

If we promptly identify those patients, a closer therapeutic drug monitoring program should be imperative with the possibility to make therapeutic interventions to improve outcomes.     

Avoidant/restrictive food intake disorder symptoms in children: Associations with child and family variables

This study sought to determine the frequency of possible cases of avoidant/restrictive food intake disorder (ARFID) in a Portuguese sample of school-aged children and to assess the associations with child’s internalizing problems, BMI z-score and body dissatisfaction, and parents’ eating habits, attitudes and practices. We assessed 330 children through child’s and parents’measures. Fifty-one (15.5%) children were possible cases of ARFID based on their symptom’s presentation. There were no association between sex and possible cases of ARFID, and no significant differences between possible cases of ARFID and nonpossible cases of ARFID regarding age. Lower BMI z-score and anxiety/depression were associated with possible cases of ARFID.     

Efficacy of a spatial repellent for control of Aedes-borne virus transmission: A cluster-randomized trial in Iquitos,Peru

Over half the world’s population is at risk for viruses transmitted by Aedes mosquitoes, such as dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are limited to Wolbachia in a single trial in Indonesia and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABVs by releasing active ingredients into the air that disrupt mosquito–human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru, to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate, and parity status through mixed-effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34.1% (one-sided 95% CI lower limit, 6.9%; one-sided P value = 0.0236, z = 1.98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28.6 (95% CI 24.1%, ∞); z = −9.11) and 12.4% (95% CI 4.2%, ∞); z = −2.43), respectively. Our trial provides conclusive statistical evidence from an appropriately powered, preplanned cluster-randomized controlled clinical trial of the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.

Aedes-borne viral diseases (ABVDs) [e.g., dengue (DENV), chikungunya, Zika (ZIKV), and yellow fever] are devastating, expanding global public health threats that disproportionally affect low- and middle-income countries. DENV, one of the most rapidly increasing vector-borne infectious diseases, results in ∼400 million infections each year (1, 2), with 4 billion people at risk for infection annually (3). Currently, the primary means for ABVD prevention is controlling the primary mosquito vector, Aedes aegypti. Existing vector control interventions, however, have failed to prevent ABV transmission and epidemics (4–6).There is an urgent need to develop evidence-based guidance for the use of new and existing ABV vector control tools. The evidence base for vector control against ABVs is weak, despite considerable government investments in World Health Organization (WHO)-recommended control of larval habitats (larviciding, container removal) and ultra-low-volume insecticide spraying (4, 5, 7–9). These strategies continue to be implemented despite the lack of rigorously generated data from controlled clinical trials demonstrating they reduce ABV infection or disease (6). The only ABV intervention with a proven epidemiological impact in a cluster-randomized control trial (cRCT) assessed community mobilization to reduce mosquito larval habitats (10). A recent test-negative trial with Wolbachia-infected mosquitoes reported a significant reduction of DENV illness in Indonesia (11).Spatial repellents (SRs) are devices that contain volatile active ingredients that disperse in air. The active ingredients can repel mosquitoes from entering a treated space, inhibit attraction to human host cues, or disrupt mosquito biting and blood-feeding behavior and, thus, interfere with mosquito–human contact (12–14). Any of these outcomes reduce the probability of pathogen transmission. Pyrethroid-based SRs have shown efficacy in reducing malaria infections in China (15) and Indonesia (16). There have, however, been no clinical trials evaluating the protective efficacy (PE) of SRs against ABV infection or disease.To generate evidence for public health consideration, we conducted a double-blinded, parallel cRCT to demonstrate and quantify the PE of a transfluthrin-based SR to reduce ABV infection incidence over 2 y in a human cohort in Iquitos, Peru.