Nasopharyngeal carriage of <i>Streptococcus pneumoniae</i> among children <5 years of age in Indonesia prior to pneumococcal conjugate vaccine introduction

by Dodi Safari, Wa Ode Dwi Daningrat, Jennifer L. Milucky, Miftahuddin Majid Khoeri, Wisiva Tofriska Paramaiswari, Wisnu Tafroji, Korrie Salsabila, Yayah Winarti, Amin Soebandrio, Sri Rezeki Hadinegoro, Ari Prayitno, Lana Childs, Fabiana C. Pimenta, Maria da Gloria Carvalho, Tamara Pilishvili

Pneumococcal conjugate vaccines (PCVs) prevent nasopharyngeal colonization with vaccine serotypes of Streptococcus pneumoniae, leading to reduced transmission of pneumococci and stronger population-level impact of PCVs. In 2017 we conducted a cross-sectional pneumococcal carriage study in Indonesia among children aged

Disabled life expectancy among older Colombian men and women

by Margarita Osuna, Mateo Farina, Jennifer Ailshire

Colombia’s population is rapidly aging and older adults are living longer, however, we have limited information on the level of disability and number of years older Colombians spend with disability. We estimated age-and-gender specific ADL, IADL and mobility disability prevalence and disabled life expectancy (DLE) and to examined gender differences. Life tables came from the Colombian vital statistics and disability prevalence data came from the cross-sectional 2015 Colombia National Survey of Health, Well-being, and Aging. Disabled life expectancy (DLE) was calculated using Sullivan’s method. About one-third to one-half of remaining years will be spent with IADL or mobility disability. The remaining years of life spent with ADL was relatively low at younger ages, but by age 85, about half of remaining life will be spent with disability. Compared to men, women had higher levels of disability and are estimated to spend more years with disability. Gender differences in ADL did not emerge until ages 70 and older. Older Colombians, in particularly women, are estimated to live a significant proportion of their life with disability, particularly IADL and mobility disability. High levels of disability are concerning because the country lacks adequate infrastructure and has limited options for long term care.

COVID-19 masks and limited number of shoppers as determinants of shop assistants’ (dis)honesty

by Maciej Koscielniak, Dorota Marciniak, Dariusz Doliński

Previous laboratory and field studies have demonstrated that the dishonesty of commercial transaction participants may depend on subtle cues. In this field study conducted on a sample of 216 shop assistants in Poland, we planned to demonstrate that coronavirus disease-related factors could result in an increased propensity for dishonesty among shop assistants. This investigation is unique in its application of social psychological theories to illuminate hitherto unexplored side effects of combating the coronavirus disease 2019 pandemic. Our supposition was that the potential detriment encountered by individuals wearing solid surgical masks would involve being viewed as more abstract and remote, thereby heightening the likelihood of being deceived by a vendor. Moreover, we examined the potential relationship between the limited number of customers in retail establishments (related to pandemic restrictions) and the unscrupulous practices of sellers—specifically the act of retaining change. The effect of wearing masks was statistically non-significant, whereas the impact of other customers’ absence was significant. Moreover, unexpected results related to transaction parties’ genders were obtained, showing that shop assistants tended to be more honest when dealing with customers of the same gender. The results are discussed in the context of empathy toward masked customers, self-awareness theory, social norms of honesty, and identification with gender groups.

Cytomegalovirus detection is associated with ICU admission in non-AIDS and AIDS patients with <i>Pneumocystis jirovecii</i> pneumonia

by Alexandre Perret, Marion Le Marechal, Raphaele Germi, Daniele Maubon, Cécile Garnaud, Johan Noble, Aude Boignard, Loïc Falque, Mathieu Meunier, Théophile Gerster, Olivier Epaulard

Objectives

Cytomegalovirus (CMV) is frequently detected in lung and/or blood samples of patients with Pneumocystis jirovecii pneumonia (PJP), although this co-detection is not precisely understood. We aimed to determine whether PJP was more severe in case of CMV detection.

Methods

We retrospectively included all patients with a diagnosis of PJP between 2009 and 2020 in our centre and with a measure of CMV viral load in blood and/or bronchoalveolar lavage (BAL). PJP severity was assessed by the requirement for intensive care unit (ICU) admission.

Results

The median age of the 249 patients was 63 [IQR: 53–73] years. The main conditions were haematological malignancies (44.2%), solid organ transplantations (16.5%), and solid organ cancers (8.8%). Overall, 36.5% patients were admitted to ICU. CMV was detected in BAL in 57/227 patients; the 37 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (78.4% vs 28.4%, p Conclusions

PJP is more severe in the case of concomitant CMV detection. This may reflect either the deleterious role of CMV itself, which may require antiviral therapy, or the fact that patients with CMV reactivation are even more immunocompromised.

Reallocating time between device-measured 24-hour activities and cardiovascular risk in Asian American immigrant women: An isotemporal substitution model

by Chorong Park, Britta Larsen, Simona C. Kwon, Yuhe Xia, Marianna LaNoue, Victoria V. Dickson, Harmony R. Reynolds, Tanya M. Spruill

The 24-hour day consists of physical activity (PA), sedentary behavior, and sleep, and changing the time spent on one activity affects the others. Little is known about the impact of such changes on cardiovascular risk, particularly in Asian American immigrant (AAI) women, who not only have a higher cardiovascular risk but also place greater cultural value on family and domestic responsibilities compared to other racial/ethnic groups. The purpose of this study was to evaluate the effects of reallocating 30 minutes of each 24-hour activity component for another on BMI, waist circumference, and blood pressure in AAI women. Seventy-five AAI women completed 7 days of hip and wrist actigraphy monitoring and were included in the analysis (age = 61.5±8.0 years, BMI = 25.5±3.6 kg/m², waist circumference = 85.9±10.2 cm). Sleep was identified from wrist actigraphy data, and moderate-to-vigorous PA (MVPA), light PA, and sedentary behavior identified from hip actigraphy data. On average, the women spent 0.5 hours in MVPA, 6.2 hours in light PA, 10 hours in sedentary activities, and 5.3 hours sleeping within a 24-hour day. According to the isotemporal substitution models, replacing 30 minutes of sedentary behavior with MVPA reduced BMI by 1.4 kg/m² and waist circumference by 4.0 cm. Replacing that same sedentary time with sleep reduced BMI by 0.5 kg/m² and waist circumference by 1.4 cm. Replacing 30 minutes of light PA with MVPA decreased BMI by 1.6 kg/m² and waist circumference by 4.3 cm. Replacing 30 minutes of light PA with sleep also reduced BMI by 0.8 kg/m² and waist circumference by 1.7 cm. However, none of the behavioral substitutions affected blood pressure. Considering AAI women’s short sleep duration, replacing their sedentary time with sleep might be a feasible strategy to reduce their BMI and waist circumference.

Impact of exercise training associated with enalapril treatment on blood pressure variability and renal dysfunctions in an experimental model of arterial hypertension and postmenopause

by Michel Pablo dos Santos Ferreira Silva, Maycon Junior Ferreira, Tânia Plens Shecaira, Danielle da Silva Dias, Débora Conte Kimura, Maria Cláudia Irigoyen, Guiomar Nascimento Gomes, Kátia De Angelis

Objective

In this study, we aimed to investigate the effects of the concurrent exercise training (CET) associated with the enalapril maleate on blood pressure variability (BPV) and renal profile in an experimental model of arterial hypertension (AH) and postmenopause.

Methods

Female ovariectomized spontaneously hypertensive rats (SHR) were distributed into 4 groups (n = 8/group): sedentary (SO), sedentary + enalapril (SOE), trained (TO) and trained + enalapril (TOE). Both enalapril (3mg/kg) and CET (3 days/week) were conducted during 8 weeks. Blood pressure (BP) was directly recorded for BPV analyses. Renal function, morphology, inflammation and oxidative stress were assessed.

Results

The SOE, TO e TOE groups presented decreased systolic BP compared with SO. Both trained groups (TO and TOE) presented lower BPV and increased baroreflex sensitivity (TO: 0.76 ± 0.20 and TOE: 1.02 ± 0.40 vs. SO: 0.40 ± 0.07 ms/mmHg) compared with SO group, with additional improvements in TOE group. Creatinine and IL-6 levels were reduced in SOE, TO and TOE compared with SO group, while IL-10 was increased only in TOE group (vs. SO). Enalapril combined with CET promote reduction in lipoperoxidation (TOE: 1.37 ± 0.26 vs. SO: 2.08 ± 0.48 and SOE: 1.84 ± 0.35 μmol/mg protein) and hydrogen peroxide (TOE: 1.89 ± 0.40 vs. SO: 3.70 ± 0.19 and SOE: 2.73 ± 0.70 μM), as well as increase in catalase activity (vs. sedentary groups). The tubulointerstitial injury was lower in interventions groups (SOE, TO and TOE vs. SO), with potentialized benefits in the trained groups.

Conclusions

Enalapril combined with CET attenuated BPV and baroreflex dysfunctions, probably impacting on end-organ damage, as demonstrated by attenuation in the AH-induced renal inflammations, oxidative stress and morphofunctional impairments in postmenopausal rats.

Regional variation and temporal trends in transcatheter and surgical aortic valve replacement in Switzerland: A population-based small area analysis

by Carla Schenker, Maria M. Wertli, Lorenz Räber, Alan G. Haynes, Arnaud Chiolero, Nicolas Rodondi, Radoslaw Panczak, Drahomir Aujesky

Background

Aortic valve stenosis (AS) is the most common valvular heart disease and if severe, is treated with either transcatheter (TAVR) or surgical aortic valve replacement (SAVR). We assessed temporal trends and regional variation of these interventions in Switzerland and examined potential determinants of geographic variation.

Methods

We conducted a population-based analysis using patient discharge data from all Swiss public and private acute care hospitals from 2013 to 2018. We generated hospital service areas (HSAs) based on patient flows for TAVR. We calculated age-standardized mean procedure rates and variation indices (extremal quotient [EQ] and systematic component of variation [SCV]). Using multilevel regression, we calculated the influence of calendar year and regional demographics, socioeconomic factors (language, insurance status), burden of disease, and number of cardiologists/cardiovascular surgeons on geographic variation.

Results

Overall, 8074 TAVR and 11,825 SAVR procedures were performed in 8 HSAs from 2013 to 2018. Whereas the age-/sex-standardized rate of TAVR increased from 12 to 22 procedures/100,000 persons, the SAVR rate decreased from 33 to 24 procedures during this period. After full adjustment, the predicted TAVR and SAVR rates varied from 12 to 22 and 20 to 35 per 100,000 persons across HSAs, respectively. The regional procedure variation was low to moderate over time, with a low overall variation in TAVR (EQ 1.9, SCV 3.9) and SAVR (EQ 1.6, SCV 2.2). In multilevel regression, TAVR rates increased annually by 10% and SAVR rates decreased by 5%. Determinants of higher TAVR rates were older age, male sex, living in a German speaking area, and higher burden of disease. A higher proportion of (semi)private insurance was also associated with higher TAVR and lower SAVR rates. After full adjustment, 10.6% of the variance in TAVR and 18.4% of the variance in SAVR remained unexplained. Most variance in TAVR and SAVR rates was explained by language region and insurance status.

Conclusion

The geographic variation in TAVR and SAVR rates was low to moderate across Swiss regions and largely explained by differences in regional demographics and socioeconomic factors. The use of TAVR increased at the expense of SAVR over time.

Screening for antibacterial and cytotoxic activities of Sri Lankan marine sponges through microfractionation: Isolation of bromopyrrole alkaloids from <i>Stylissa massa</i>

by Lakmini Kosgahakumbura, Jayani Gamage, Luke P. Robertson, Taj Muhammad, Björn Hellman, Ulf Göransson, Prabath Jayasinghe, Chamari Hettiarachchi, Paco Cárdenas, Sunithi Gunasekera

Sri Lanka is a biodiversity hotspot and one of the richest geographical locations of marine sponges in the Indian ocean. However, the most extensive taxonomical study on Sri Lankan sponge biodiversity dates back ~100 years and only a limited number of studies have been conducted on sponge natural products. In the current study, 35 marine sponge specimens (collected from 16 sponge habitats around Sri Lanka) were identified, microfractionated and evaluated for antibacterial and anticancer assays. In total, 30 species were characterized, of which 19 species gave extracts with antibacterial and/or cytotoxic activities. Microfractionated organic extract of Aciculites orientalis gave the most potent antibacterial activity against Staphylococcus aureus and strongest lymphoma cell toxicity was exhibited by the organic extract of Acanthella sp. Guided by the molecular ion peaks in the bioactive fractions, large-scale extraction of Stylissa massa led to the isolation of three bromopyrrole alkaloids, sceptrin, hymenin and manzacidin A/C. Of these, sceptrin exhibited broad spectrum antibacterial activity against both Escherichia coli and S. aureus (MIC of 62.5 μM against both species). Based on natural product literature, seven promising species were identified as understudied. Their further exploration may lead to the discovery of structurally novel compounds.

Patient and caregiver perspectives of select non-communicable diseases in India: A scoping review

by Sindhu Nila, Eliza Dutta, S. S. Prakash, Sophy Korula, Anu Mary Oommen

Background and objectives

Patient-reported measures of encounters in healthcare settings and consideration of their preferences could provide valuable inputs to improve healthcare quality. Although there are increasing reports of user experiences regarding health care in India in recent times, there is a lack of evidence from Indian healthcare settings on the care provided for patients with chronic diseases.

Methods

We selected diabetes mellitus and cancer as representatives of two common conditions requiring different care pathways. We conducted a scoping review of studies reporting experiences or preferences of patients/caregivers for these conditions, in PubMed, Global Index Medicus and grey literature, from the year 2000 onwards. Both published and emergent themes were derived from the data and summarised as a narrative synthesis.

Results

Of 95 included studies (49 diabetes, 46 cancer), 73% (65) were exclusively quantitative surveys, 79% included only patients (75), and 59.5% (44) were conducted in government centres. Studies were concentrated in a few states in India, with the underrepresentation of vulnerable population groups and representative studies. There was a lack of standardised tools and comprehensive approaches for assessing experiences and preferences of patients and caregivers, concerning diabetes and cancers in India. The commonest type of care assessed was therapeutic (74), with 14 cancer studies on diagnosis and nine on palliative care. Repeated visits to crowded centres, drug refill issues, unavailability of specific services in government facilities, and expensive private care characterised diabetes care, while cancer care involved delayed diagnosis and treatment, communication, and pain management issues.

Conclusions

There is a need for robust approaches and standardised tools to measure responsiveness of the healthcare system to patient needs, across geographical and population subgroups in India. Health system reforms are needed to improve access to high-quality care for treatment and palliation of cancer and management of chronic diseases such as diabetes.

Detection of CTLA-4 level and humeral immune response after the second dose of COVID-19 vaccine in certain Iraqi provinces participants

by Laith A. I. K. Al-Kaif, Hussain Al-Ameri, Wael Rasheed Obaead Alfatlawi, Ammar Eesa Mahdi, Younis A. K. Al-Khafaji, Mohammad Abd-Kadhum Al-Saadi, Alaa H. Al-Charrakh, Raheem T. Al-Mammori, Mohammed Ahmed Akkaif

Background

Evaluating immune responses following COVID-19 vaccination is paramount to understanding vaccine effectiveness and optimizing public health interventions. This study seeks to elucidate individuals’ immune status after administering a second dose of diverse COVID-19 vaccines. By analyzing immune responses through serological markers, we aim to contribute valuable insights into the uniformity of vaccine performance.

Methods

A total of 80 participants were enrolled in this study, with demographic and COVID-19 infection-related data collected for categorization. Serum samples were acquired within a specified timeframe, and SARS-CoV-2 IgM/IgG rapid tests were conducted. Moreover, CTLA-4 levels were measured through ELISA assays, allowing us to assess the immune responses comprehensively. The participants were divided into eight groups based on various factors, facilitating a multifaceted analysis.

Results

The outcomes of our investigation demonstrated consistent immune responses across the diverse types of COVID-19 vaccines administered in Iraq. Statistical analysis revealed no significant distinctions among the vaccine categories. In contrast, significant differences were observed in CTLA-4 among the control group (non-infected/non-vaccinated, infected/non-vaccinated) and infected/Pfizer, non-infected/Pfizer, and infected/Sinopharm, non-infected/sinopharm (P = 0.001, Conclusions

In conclusion, our study’s results underscore the lack of discriminatory variations between different COVID-19 vaccine types utilized in Iraq. The uniform immune responses observed signify the equitable efficacy and performance of these vaccines. Despite minor quantitative discrepancies, these variations do not hold statistical significance, reaffirming the notion that the various vaccines serve a similar purpose in conferring protection against COVID-19.

Molecular effects of polystyrene nanoplastics on human neural stem cells

by Raquel Martin-Folgar, Mª Carmen González-Caballero, Mónica Torres-Ruiz, Ana I. Cañas-Portilla, Mercedes de Alba González, Isabel Liste, Mónica Morales

Nanoplastics (NPs) have been found in many ecological environments (aquatic, terrestrial, air). Currently, there is great concern about the exposition and impact on animal health, including humans, because of the effects of ingestion and accumulation of these nanomaterials (NMs) in aquatic organisms and their incorporation into the food chain. NPs´ mechanisms of action on humans are currently unknown. In this study, we evaluated the altered molecular mechanisms on human neural stem cell line (hNS1) after 4 days of exposure to 30 nm polystyrene (PS) NPs (0.5, 2.5 and 10 μg/mL). Our results showed that NPs can induce oxidative stress, cellular stress, DNA damage, alterations in inflammatory response, and apoptosis, which could lead to tissue damage and neurodevelopmental diseases.

Analysing food farming vulnerability in Kalimantan, Indonesia: Determinant factors and adaptation measures

by Woro Estiningtyas, Elza Surmaini, Suciantini, Erni Susanti, Anny Mulyani, Budi Kartiwa, Sumaryanto, Perdinan, Yayan Apriyana, Annisa Dhienar Alifia

As a result of plans to relocate the Indonesian capital city to East Kalimantan province, Kalimantan is expected to develop rapidly and the surrounding regencies and provinces will become food support areas for the new capital. However, the vulnerability of food farming in Kalimantan is a concern that must be addressed to ensure food security. This study aims to assess the vulnerability of food farming at the regency level of the island of Kalimantan, to assess the determinant factors of the food farming vulnerability and to compose adaptation measures that can reduce vulnerability. Socio economic, climate, water and land data are sorted and analyzed to represent the level of sensitivity and exposure index (SEI) and adaptive capacity index (ACI). Locations with ‘High’ and ‘Very High’ levels of farming vulnerability become interview sites with a total of 150 respondents. The results of the interviews strengthen the results of the vulnerability analysis which helps to determine the condition of farmers and food farming in vulnerable locations. The results indicated ‘Very High’ and ‘High’ level of vulnerability in 14 regencies/cities. Floods are climate-related disasters that most often affect farmers surveyed (46%), followed by droughts (30%) and pest attacks (24%) with significant impacts (49%). The identification of the determinant factors becomes the basis for adaptive measures to support decision-makers, local practitioners, and farmers by highlighting local challenges and proposing local-specific adaptation strategies.

Effects of service dogs on children with ASD’s symptoms and parents’ well-being: On the importance of considering those effects with a more systemic perspective

by Nicolas Dollion, Margot Poirier, Florian Auffret, Nathe François, Pierrich Plusquellec, Marine Grandgeorge, Handi’Chiens , Fondation Mira

The integration of a service dog can have numerous benefits for children with Autism Spectrum Disorder (ASD). However, although integration takes place within a family, little is known about the dynamics of these benefits on the family microsystem. Thus, the aim of our study was to propose a more systemic perspective, not only by investigating the benefits of SD integration, but also by exploring the relationships between improvements in children with ASD, parents’ well-being, parenting strategies and the quality of the child-dog relationship. Twenty parent-child with ASD dyads were followed before, as well as 3 and 6 months after service dog integration. At each stage, parents completed an online survey which included: the Autism Behavior Inventory (ABI-S), the State-Trait Anxiety Inventory (STAI-Y), the Parenting Stress Index Short Version (PSI-SF), the Monash Dog Owner Relationship Scale (MDORS) and the Parenting Styles and Dimensions Questionnaire (PSDQ). First, repeated measure one-way ANOVAs revealed that both children’s ASD symptoms and parents’ anxiety decreased significantly after service dog integration. Additionally, Spearman correlations revealed that the more ASD symptoms decreased, the more parent’s anxiety and parenting stress also decreased. Second, the quality of the child-dog relationship appeared to contribute to those benefits on both children’s ASD symptoms and parents’ well-being. Interestingly, parenting strategies seemed to adapt according to these benefits and to the quality of the child-dog relationship. Through a more systemic perspective, this study highlighted that the integration of a service dog involved reciprocal and dynamic effects for children with ASD and their parents, and shed new light on the processes that may underlie the effects of a service dog for children with ASD.

Identification of viral protein R of human immunodeficiency virus-1 (HIV) and interleukin-6 as risk factors for malignancies in HIV-infected individuals: A cohort study

by Akihiro Matsunaga, Naokatsu Ando, Yuko Yamagata, Mari Shimura, Hiroyuki Gatanaga, Shinichi Oka, Yukihito Ishizaka

Background

Despite effective antiretroviral therapy, patients with human immunodeficiency virus type-1 (HIV) suffer from a high frequency of malignancies, but related risk factors remain elusive. Here, we focused on blood-circulating viral protein R (Vpr) of HIV, which induces proinflammatory cytokine production and genotoxicity by exogenous functions.

Methods and findings

A total 404 blood samples of HIV patients comprising of 126 patients with malignancies (tumor group) and 278 patients without malignancies (non-tumor group), each of 96 samples was first selected by one-to-one propensity score matching. By a detergent-free enzyme-linked immunosorbent assays (detection limit, 3.9 ng/mL), we detected Vpr at a higher frequency in the matched tumor group (56.3%) than in the matched non-tumor group (39.6%) (P = 0.030), although there was no different distribution of Vpr levels (P = 0.372). We also detected anti-Vpr immunoglobulin (IgG), less frequently in the tumor group compared with the tumor group (22.9% for tumor group vs. 44.8% for non-tumor group, P = 0.002), and the proportion of patients positive for Vpr but negative of anti-Vpr IgG was significantly higher in the tumor group than in the non-tumor group (38.6% vs. 15.6%, respectively, P P P P = 0.010). Finally, multivariate logistic regression analysis suggested a positive link of Vpr with tumor occurrence in HIV patients (P = 0.002).

Conclusion

Vpr and IL-6 could be risk factors of HIV-1 associated malignancies, and it would be importance to monitor these molecules for well managing people living with HIV-1.

The role of basic psychological needs in the relationships between identity orientations and adolescent mental health: A protocol for a longitudinal study

by Veljko Jovanović, Aleksandar Tomašević, Dušana Šakan, Milica Lazić, Vesna Gavrilov-Jerković, Marija Zotović-Kostić, Vojana Obradović

Research into the role of identity orientations (the relative importance an individual places on different personal and social attributes and characteristics when defining her or his identity) in adolescent mental health is extremely limited. Furthermore, the potential mechanisms that might explain the associations between identity orientations and adolescent mental health are poorly understood. This study protocol describes a one-year longitudinal study across three time points to be initiated with the purpose of investigating the mediating role of basic psychological needs satisfaction and frustration in the relationship between identity orientations and various mental health indicators in adolescence. We aim to recruit a large sample of Serbian adolescents (N = 2,000 at Time 1), using a two-stage stratified random sampling. The data will be analyzed using the random intercept cross-lagged panel model (RI-CLPM), and the results will be contrasted with the traditional CLPM. The goal of this study is to make a theoretical contribution to research in the fields of identity, self-determination theory, and adolescent mental health, as well as to provide insights towards the development of evidence-based recommendations for creating prevention and promotion programs aimed at improving the well-being of adolescents.

Feasibility and metabolic outcomes of a well-formulated ketogenic diet as an adjuvant therapeutic intervention for women with stage IV metastatic breast cancer: The Keto-CARE trial

by Alex Buga, David G. Harper, Teryn N. Sapper, Parker N. Hyde, Brandon Fell, Ryan Dickerson, Justen T. Stoner, Madison L. Kackley, Christopher D. Crabtree, Drew D. Decker, Bradley T. Robinson, Gerald Krystal, Katherine Binzel, Maryam B. Lustberg, Jeff S. Volek

Purpose

Ketogenic diets may positively influence cancer through pleiotropic mechanisms, but only a few small and short-term studies have addressed feasibility and efficacy in cancer patients. The primary goals of this study were to evaluate the feasibility and the sustained metabolic effects of a personalized well-formulated ketogenic diet (WFKD) designed to achieve consistent blood beta-hydroxybutyrate (βHB) >0.5 mM in women diagnosed with stage IV metastatic breast cancer (MBC) undergoing chemotherapy.

Methods

Women (n = 20) were enrolled in a six month, two-phase, single-arm WFKD intervention (NCT03535701). Phase I was a highly-supervised, ad libitum, personalized WFKD, where women were provided with ketogenic-appropriate food daily for three months. Phase II transitioned women to a self-administered WFKD with ongoing coaching for an additional three months. Fasting capillary βHB and glucose were collected daily; weight, body composition, plasma insulin, and insulin resistance were collected at baseline, three and six months.

Results

Capillary βHB indicated women achieved nutritional ketosis (Phase I mean: 0.8 mM (n = 15); Phase II mean: 0.7 mM (n = 9)). Body weight decreased 10% after three months, primarily from body fat. Fasting plasma glucose, plasma insulin, and insulin resistance also decreased significantly after three months (p Conclusions

Women diagnosed with MBC undergoing chemotherapy can safely achieve and maintain nutritional ketosis, while improving body composition and insulin resistance, out to six months.

Heterogenous circulating miRNA changes in ME/CFS converge on a unified cluster of target genes: A computational analysis

by Mateusz Piotr Kaczmarek

Myalgic Encephalomyelitis / Chronic Fatigue Syndrome is a debilitating, multisystem disease of unknown mechanism, with a currently ongoing search for its endocrine mediators. Circulating microRNAs (miRNA) are a promising candidate for such a mediator and have been reported as significantly different in the patient population versus healthy controls by multiple studies. None of these studies, however, agree with each other on which specific miRNA are under- or over-expressed. This discrepancy is the subject of the computational study presented here, in which a deep dive into the predicted gene targets and their functional interactions is conducted, revealing that the aberrant circulating miRNAs in ME/CFS, although different between patients, seem to mainly target the same specific set of genes (p ≈ 0.0018), which are very functionally related to each other (p ≲ 0.0001). Further analysis of these functional relations, based on directional pathway information, points to impairments in exercise hyperemia, angiogenic adaptations to hypoxia, antioxidant defenses, and TGF-β signaling, as well as a shift towards mitochondrial fission, corroborating and explaining previous direct observations in ME/CFS. Many transcription factors and epigenetic modulators are implicated as well, with currently uncertain downstream combinatory effects. As the results show significant similarity to previous research on latent herpesvirus involvement in ME/CFS, the possibility of a herpesvirus origin of these miRNA changes is also explored through further computational analysis and literature review, showing that 8 out of the 10 most central miRNAs analyzed are known to be upregulated by various herpesviruses. In total, the results establish an appreciable and possibly central role for circulating microRNAs in ME/CFS etiology that merits further experimental research.

Gait analysis: An effective tool to mechanically monitor the bone regeneration of critical-sized defects in tissue engineering applications

by Pablo Blázquez-Carmona, Juan Mora-Macías, Juan Morgaz, María del Mar Granados, Jaime Domínguez, Esther Reina-Romo

Introduction

Tissue engineering has emerged as an innovative approach to treat critical-size bone defects using biocompatible scaffolds, thus avoiding complex distraction surgeries or limited stock grafts. Continuous regeneration monitoring is essential in critical-size cases due to the frequent appearance of non-unions. This work evaluates the potential clinical use of gait analysis for the mechanical assessment of a tissue engineering regeneration as an alternative to the traditional and hardly conclusive manual or radiological follow-up.

Materials and methods

The 15-mm metatarsal fragment of eight female merino sheep was surgically replaced by a bioceramic scaffold stabilized with an external fixator. Gait tests were performed weekly by making the sheep walk on an instrumented gangway. The evolution of different kinematic and dynamic parameters was analyzed for all the animal’s limbs, as well as asymmetries between limbs. Finally, potential correlation in the recovery of the gait parameters was evaluated through the linear regression models.

Results

After surgery, the operated limb has an altered way of carrying body weight while walking. Its loading capacity was significantly reduced as the stance phases were shorter and less impulsive. The non-operated limbs compensated for this mobility deficit. All parameters were normalizing during the consolidation phase while the bone callus was simultaneously mineralizing. The results also showed high levels of asymmetry between the operated limb and its contralateral, which exceeded 150% when analyzing the impulse after surgery. Gait recovery significantly correlated between symmetrical limbs.

Conclusions

Gait analysis was presented as an effective, low-cost tool capable of mechanically predicting the regeneration of critical-size defects treated by tissue engineering, as comparing regeneration processes or novel scaffolds. Despite the progressive normalization as the callus mineralized, the bearing capacity reduction and the asymmetry of the operated limb were more significant than in other orthopedic alternatives.

Screening for the risk of canine impaction, what are the presumptive signs and how does it affect orthodontics? A cross-sectional study in France

by Damien Brézulier, Steeven Carnet, Alexia Marie-Cousin, Jean-Louis Sixou

Purpose

The treatment of impacted canines is a challenge for orthodontists. The availability of suggestive clinical signs has become crucial for treatment before the potential for evolution ceases. The main objective was to evaluate the prevalence of the suspected displaced canine (SDC) and to highlight factors easily identifiable from the oral examination.

Methods

SDC was assessed on panoramic X-rays, on the basis of the angle with the median sagittal plane and the degree of overlap with the permanent lateral incisor. Its association with mesio-distal tooth and palate widths was assessed by univariate analysis. Next, the association of SDC with temporary tooth extraction, expansion and/or premolar extraction was considered using the same modality.

Results

In this retrospective study, the records of 292 patients aged 7 to 13 years were reviewed. SDC was detected in 39% of patients i.e., 28,8% of observed canines. Reduced coronal mesio-distal diameters of permanent maxillary central incisors, 8.7 ± 0.6 mm versus 8.8 ± 0.7 mm (p Conclusion

This study confirmed the interest of panoramic X-rays in detected canines at risk of SDC. Dental factors can be combined to make screening more reliable and predict impaction that makes orthodontics complex.

Trial registration number

Opinion n°21.131, dated 09.21.2021, retrospectively registered.

Puberty, brain network connectivity and neuropsychiatric outcomes following pediatric traumatic brain injury in females: A research protocol

by Abigail Livny, Tamar Silberg

Background

Examining the role of sex on recovery from pediatric TBI (pTBI) is a complex task, specifically when referring to injuries occurring during critical developmental and maturation periods. The effect of sex hormones on neurological and neuropsychiatric outcomes has been studied among adult TBI females, but not in children. During development, puberty is considered a key milestone accompanied by changes in physical growth, neuronal maturation, sex hormones, and psychological symptoms. Following pTBI, such changes might have a significant effect on brain re-organization and on long-term neuropsychiatric outcomes. While hormonal dysfunction is a common consequence following pTBI, only few studies have systematically evaluated hormonal changes following pTBI.

Aims

To describe a multimodal protocol aimed to examine the effect of puberty on brain connectivity and long-term neuropsychiatric outcomes following TBI in female girls and adolescents.

Methods

A case-control longitudinal prospective design will be used. 120 female participants aged 9 to 16 years (N = 60 per group) will be recruited. In the acute phase (T0-1 month), participants will undergo an MRI protocol for brain connectivity, as well as a clinical evaluation for puberty stage and hormonal levels. In the chronic phase (T1-18-24 months), participants will complete a neuropsychiatric assessment in addition to the MRI and puberty evaluations. Hormonal levels will be monitored at T0 and T1. A moderation-mediation model will be used to examine the moderating effects of puberty on the association between pTBI and neuropsychiatric symptoms in female girls and adolescents, through the mediating effect of brain network connectivity.

Significance

This study will highlight sex-specific factors related to outcomes among females following pTBI and enhance our understanding of the unique challenges they face. Such information has a substantial potential to guide future directions for research, policy and practice.