bluuebunny/crossref_metadata_2025 huggingface dataset:
Anemia is a novel predictor for clinical ISR following PCI
Authors: Hussein Ahmed , Awad Mohammad Shafiq , Sabra Ahlam M. , Mahmoud Hossam Eldin M.
Published: May 2021

Background

Conflicting data were found regarding the anemia’s effect on percutaneous coronary intervention (PCI) outcomes. We directed our study to investigate anemia’s effect on clinical in-stent restenosis (ISR) following PCI.

Results

A prospective multi-center cohort study was performed on 470 consecutive participants undergoing elective PCI. We classified the participants into two groups: group 1 who were anemic and group 2 who were non-anemic as a control group. At 1, 3, 6, and 12 months by clinic visits, we followed up with the patients to assess anemia’s clinical ISR effect. We found that 20% of the patients undergoing PCI had anemia. Anemic patients showed a statistically significant higher rate of impaired renal function and diabetes and a higher percentage of the female gender. Multivariate regression analysis for major adverse cardiovascular events (MACEs) after adjusting for confounding factors revealed that anemia represents a more risk on MACE (adjusted hazard ratio (HR) was 4.13; 95% CI 2.35–7.94; p value < 0.001) and carries a higher risk upon clinical ISR (adjusted HR was 3.51; 95% CI 1.88–7.16; p value < 0.001) over 12 months of follow-up.

Conclusion

Anemic patients going through PCI are generally females, diabetics, and have renal impairment. Anemia might be considered another indicator for clinical ISR and is fundamentally associated with an increased MACE incidence.
Rivaroxaban versus warfarin for the management of left ventricle thrombus
Authors: Albabtain Monirah A. , Alhebaishi Yahya , Al-Yafi Ola , Kheirallah Hatim , Othman Adel , Alghosoon Haneen , Arafat Amr A. , Alfagih Ahmed
Published: May 2021

Background

Rivaroxaban has been recently introduced for the management of non-valvular intra-cardiac thrombosis with variable results. We aimed to compare the results of the off-label use of rivaroxaban versus warfarin in the management of patients with left ventricle (LV) thrombus. This research is a retrospective study conducted on 63 patients who had LV thrombus from January to December 2016. We compared patients treated with warfarin (n=35) to patients who had rivaroxaban (n=28), and study outcomes were time to thrombus resolution, bleeding, stroke, and mortality.

Results

The median duration of treatment was 9.5 (25th-75th percentiles: 6-32.5) months for rivaroxaban and 14 (3-41) months for warfarin. Thrombus resolution occurred in 24 patients in the warfarin group (68.6%) and 20 patients in the rivaroxaban group (71.4%). The median time to resolution in the warfarin group was 9 (4-20) months and 3 (2-11.5) months in the rivaroxaban group. Thrombus resolution was significantly faster in patients on rivaroxaban (p= 0.019). Predictors of thrombus resolution were thrombus surface area (HR: 1.21; CI 95% (1.0-1.46); p= .048) and the use of rivaroxaban (HR: 1.92; CI 95% (1.01-3.65); p= 0.048). There was no difference in stroke, bleeding, and mortality between both groups.

Conclusion

Rivaroxaban was as effective and safe as warfarin in managing patients with left ventricle thrombus. Larger randomized clinical trials are recommended to confirm our findings.
Spontaneous pulmonary artery thrombus in a neonate
Authors: Shrimanth Y. S. , Prasad Krishna , Karthik Adari Appala , Barwad Parag , Pruthvi C. R. , Gawalkar Atit A. , Santosh Krishna , Naganur Sanjeev
Published: May 2021

Background

Pulmonary artery thrombosis is rare in neonates and mimics as persistent pulmonary hypertension or congenital heart disease. Risk factors include septicemia, dehydration, polycythemia, maternal diabetes, asphyxia, and inherited thrombophilias. They present with cyanosis and respiratory distress. Careful echocardiogram assessment helps in identifying the thrombus in the pulmonary artery and its branches. Computed tomography pulmonary angiography confirms the diagnosis.

Case presentation

We present a case of term neonate who presented with respiratory distress and cyanosis and a detailed echocardiogram revealed thrombus in the origin of left pulmonary artery. The neonate was managed initially with unfractionated heparin and later with low molecular weight heparin with which there was significant resolution of the thrombus

Conclusion

Spontaneous pulmonary artery thrombosis though rare should be suspected in any cyanotic neonate with respiratory distress. Management in these cases depends on the haemodynamic instability and lung ischemia.
Severe post-traumatic disorder leading to failure of passing asylum interview—a case report
Authors: Sarangi Ashish , Deleon Sabrina , Baronia Regina , Jimenez Rosalinda , Ibrahim Yasin
Published: May 2021

Background

Asylum applicants can benefit from psychiatric evaluation which can explain how culture and mental health symptoms relate to perceived deficits in credibility.

Case presentation

Ms. B presented for psychiatric evaluation, seeking asylum in the USA after multiple threats on her life in Honduras. At initial evaluation, she was diagnosed with depression. On reevaluation, she was found to have panic attacks and post-traumatic stress disorder. Recommendations included an anxiolytic medication and the use of pre-written statements upon interview. However, Ms. B was sent back to her country of origin despite her severe mental symptoms.

Conclusion

Post-traumatic disorder scales should be used by mental health professionals especially with patients who are not forthcoming about past trauma history to avoid missing this diagnosis. There is a need to inform immigration officials and lawyers about the necessity of accommodating clients’ needs to appropriately present themselves in asylum interviews.
The analysis of the degree of 10–13-year-old children’s nutrition, dietary habits and physical activity in the selected rural and urban areas of Silesian Province (Poland)
Authors: Jonczyk Paweł , Potempa-Jeziorowska Magdalena , Świętochowska Elżbieta , Kucharzewski Marek
Published: May 2021

Background

The nutrition disorders in the children’s population, in the form of malnutrition, as well as overweight and obesity constitute a significant clinical problem in the contemporary world. As a result of the improper way of children’s nutrition, their physical and mental development becomes dysfunctional, which leads in their adult life to serious health consequences, among others, complications of cardiovascular system, metabolic and endocrinological and disorders, improper development of osteoarticular system and mental diseases and social withdrawal.

Results

Five hundred eighty-nine parents of children aged 10–13 participated in the survey questionnaire, where 304 respondents were constituted by girls (51.61%); however, the remaining 285 people were represented by boys (48.39%). It turned out that overweight and obesity concern approximately 44% of respondents; however, approximately 22% of children have too low body weight in relation to age and sex. While analysing dietary habits, it was observed that main meals are not consumed by all children; breakfast is consumed by approximately 90% of respondents, packed lunch just by 70% and lunch and supper by 90% of respondents. In the course of subsequent analyses, it turned out that over ¾ of respondents declared that their child drinks mineral water every day, only approximately 44% of them drink milk every day; however, almost 18% of children reach for sweet drinks. Children eat sweet or salty snacks too often (over 55% every day or several times a week), resigning from consuming fruit and vegetables (just half of respondents every day), fish and brown bread (below 30% of children eat these products less than once a week); every fifth child dedicates less than 3 h to physical activity, 39% of respondents do exercise from 3 to 5 h a week, the next 25% from 5 to 10 h.

Conclusions

It was observed in the analysed population that over half of them struggle with the degree of nutrition disorders in the form of overweight and obesity or malnutrition. We may conclude, based on the obtained results, that children have inappropriate dietary habits, consuming too small quantities of fruit and vegetables, brown bread, fish and drinking improper quantities of water and milk. Repeatedly, they replace these full-value products by consuming sweets and salty snacks and by drinking sweet drinks, they also more and more often reach for processed food in fast food bars. What is worrying, it was also observed that in the analysed population, children dedicate too little of their free time to physical activity and additional physical activities.
Predicting lung fibrosis in post-COVID-19 patients after discharge with follow-up chest CT findings
Authors: Yasin Rabab , Gomaa Ahmed Abdelhakim Kamel , Ghazy Tamer , Hassanein Shaimaa Abdelhamid , Ibrahem Reda Abdel latif , Khalifa Mohamed Hossameldin
Published: May 2021

Background

Coronavirus disease has spread widely all over the world since the beginning of 2020, and this required rapid adequate management. High-resolution computed tomography (HRCT) has become an initial valuable tool for screening, diagnosis, and assessment of disease severity. This study aimed to assess the clinical, radiographic, and laboratory findings of COVID-19 with HRCT follow-up in discharged patients to predict lung fibrosis after COVID-19 infection in survived patients.

Results

This study included two-hundred and ten patients who were tested positive for the novel coronavirus by nasopharyngeal swap, admitted to the hospital, and discharged after recovery. Patients with at least a one-time chest CT scan after discharge were enrolled. According to the presence of fibrosis on follow-up CT after discharge, patients were classified into two groups and assigned as the “non-fibrotic group” (without evident fibrosis) and “fibrotic group” (with evident fibrosis). We compared between these two groups based on the recorded clinical data, patient demographic information (i.e., sex and age), length of stay (LOS) in the hospital, admission to the ICU, laboratory results (peak C-reactive protein [CRP] level, lowest lymphocyte level, serum ferritin, high-sensitivity troponin,d-dimer, administration of steroid), and CT features (CT severity score and CT consolidation/crazy-paving score). CT score includes the CT during the hospital stay with peak opacification and follow-up CT after discharge. The average CT follow-up time after discharge is 41.5 days (range, 20 to 65 days). There was a statistically significant difference between both groups (p˂0.001). Further, a multivariate analysis was performed and found that the age of the patients, initial CT severity score, consolidation/crazy-paving score, and ICU admission were independent risk factors associated with the presence of post-COVID-19 fibrosis (p<0.05). Chest CT severity score shows a sensitivity of 86.1%, a specificity of 78%, and an accuracy of 81.9% at a cutoff point of 10.5.

Conclusion

The residual pulmonary fibrosis in COVID-19 survivors after discharge depends on many factors with the patient’s age, CT severity, consolidation/crazy-paving scores, and ICU admission as independent risk factors associated with the presence of post-COVID-19 fibrosis.
Evaluation of bone healing activity of Cissus quadrangularis (Linn), Cryptolepis buchanani, and Sardinella longiceps in Wistar rats
Authors: Ramachandran Somasundaram , Fadhil Laith , Gopi Chandravadivelu , Amala Masa , Dhanaraju Magharla Dasaratha
Published: May 2021

Background

The object of the present study is to evaluate the effect of alcoholic extracts of Cissus quadrangularis (CQ), Cryptolepis buchanani (CB), and Sardinella longiceps (SL) either alone or in the combination (100 mg/kg) in the management of femur bone healing of Wistar albino rats for 8 weeks. After the period of treatment, femur bones were examined by using biochemical, radiographical, and histopathological studies.

Result

Biochemical evaluation results reveal that there is a steep increase of serum calcium level in the experimental animals during the entire period of treatment which led to an adequate supply of serum calcium to the fractured bone for healing and increases the thickness of the femur bones soon compared to control group. It had been estimated by a calibrated ocular micrometer. Radiographical images of the bones also disclose that the complete bridging of fractured bone occurred in the experimental animals after the treatment of natural compound extracts. In addition to that, all the organs of animals were safe in the experimental animals during the entire study.

Conclusion

The present study strongly recommended that these ethanolic extracts (CQCBSL) either alone or in the combination restoring the strength of the bone and reduced bone repairing period due to the rich content of calcium and other natural phytochemicals presents with them.

Graphical abstract
Descriptive analysis of the development of the Arabic speech sounds among typically developing colloquial Egyptian Arabic-speaking children
Authors: Elrefaie Dina Ahmed , Hegazi Mona Abd El-Fattah , El-Mahallawi Marwa Mohammed , Khodeir Mona Sameeh
Published: May 2021

Background

Literature only mentioned a few kinds of research that did study the development of the speech sounds of the Colloquial Egyptian Arabic dialect. Moreover, these studies focused on describing the phonological processes that children undergo in early childhood rather than describing the exact time of acquisition of these sounds. Besides, no study involved a statistically enough sample size of children across the different age ranges. Thus, this study aimed to explore the development of the Arabic phonemes among 360 typically developing Egyptian children who speak the CEA dialect, between the ages of 1.6 years and ≤ 7.4 years.

Results

The results of a 93-picture-naming test of children were analyzed. A phoneme is considered acquired when 90% of the children could properly utter the target phoneme in all word positions and mastered when 100% of children could correctly pronounce the target phoneme in all word positions. The results revealed that by the age of 1.6–2.0 years, the 6 long vowels of the CEA dialect, besides the /h/,/ʔ/, /b/, /w/, /j/, /m/, and /n/ were mastered. /t/ and /d/ sounds were mastered by the age of 2.6 years followed by /l/ sound by the age of 3.0 years. Then, /ħ/, /ʕ/ sounds were mastered followed by /k/, and /g/ at the age of 3.0 and 3.6 years, respectively. At the age of 5.0 years, /f/ sound was mastered, then /x / and /ʃ/ sounds were mastered by the age of 4.6 years, followed by /s/, /sˁ/, /tˁ/, /dˁ/. By the age of 5.6 and 6.0 years, /ɣ/, /r/, and /z/ were mastered. The /q/, /θ/, /ð/, and /ðˁ/ sounds were mastered by the age of 6.0–6.6 years. This study revealed that fricative sounds developed before the stop sounds and front stops before the back stops, and emphatic Arabic sounds were the last to develop at the school age (> 5 years).

Conclusions

This study presented a chart of the development of the Arabic phonemes of the CEA to be used as a guide to decide upon the correct trimming to start articulatory therapy for children with articulation and/or phonological disorders.
Microplastics have shape- and polymer-dependent effects on soil aggregation and organic matter loss – an experimental and meta-analytical approach
Authors: Lehmann Anika , Leifheit Eva F. , Gerdawischke Maurice , Rillig Matthias C.
Published: May 2021

Microplastics are a diverse and ubiquitous contaminant, a global change driver with potential to alter ecosystem properties and processes. Microplastic-induced effects in soils are manifold as microplastics differ in a variety of properties among which the shape is of special interest. Our knowledge is limited regarding the impact of various microplastic shapes on soil processes. Therefore, we conducted this two-part research comprising a meta-analysis on published literature and a lab experiment focusing on microplastic shapes- and polymer-induced effects on soil aggregation and organic matter decomposition. We here focus on fibers, films, foams and particles as microplastic shapes.

In the meta-analysis, we found a strong research focus on fibrous and particulate microplastic materials, with films and foams neglected.

Our experiment showed that microplastic shapes are important modulators of responses in soil aggregation and organic matter decomposition. Fibers, irrespective of their chemistry, negatively affected the formation of aggregates. However, for other shapes like foams and particles, the polymer identity is an important factor co-modulating the soil responses.

Further research is needed to generate a data-driven foundation to permit a better mechanistic understanding of the importance and consequences of microplastics added to soils.
The Effects of Estrogens on Neural Circuits That Control Temperature
Authors: Zhang Zhi , DiVittorio Johnathon R , Joseph Alexia M , Correa Stephanie M
Published: May 2021

Declining and variable levels of estrogens around the time of menopause are associated with a suite of metabolic, vascular, and neuroendocrine changes. The archetypal adverse effects of perimenopause are vasomotor symptoms, which include hot flashes and night sweats. Although vasomotor symptoms are routinely treated with hormone therapy, the risks associated with these treatments encourage us to seek alternative treatment avenues. Understanding the mechanisms underlying the effects of estrogens on temperature regulation is a first step toward identifying novel therapeutic targets. Here we outline findings in rodents that reveal neural and molecular targets of estrogens within brain regions that control distinct components of temperature homeostasis. These insights suggest that estrogens may alter the function of multiple specialized neural circuits to coordinate the suite of changes after menopause. Thus, defining the precise cells and neural circuits that mediate the effects of estrogens on temperature has promise to identify strategies that would selectively counteract hot flashes or other negative side effects without the health risks that accompany systemic hormone therapies.
Abnormal Non Esterified Fatty Acid Suppression After a Mixed Meal Test in Patients With Partial Lipodystrophy
Authors: de Freitas Maria Cristina Foss , Akinci Baris , Oral Elif A
Published: May 2021

Elevated levels of non-esterified fatty acids (NEFA) have been observed in individuals with several clinical scenarios of insulin resistance, such as in diabetes mellitus and lipodystrophy. Insulin is a well-known stimulator of de novo lipogenesis. Despite the reduction of adipose tissue mass, paradoxically elevated circulating NEFA concentrations have been observed in patients with different lipodystrophy syndromes. Aiming to understand the behavior of NEFA in lipodystrophy versus common Type 2 diabetes mellitus during feeding, we compared NEFA kinetics during a mixed meal test in patients with partial lipodystrophy (PL) and Type 2 diabetes mellitus (DM). We reviewed data from 17 PL patients (13F/4M, ages 12–64) matched by gender and BMI to 20 DM patients (13F/7M, ages 24–72). All patients were evaluated during fasting state and then underwent a mixed meal test (MMT). Blood samples were collected before (fasting) and at 30, 60, 90, 120, and 180 minutes post-meal to measure glucose, insulin, non-esterified free fatty acids (NEFA), and triglyceride levels. Adipose tissue insulin resistance (ADIPO-IR) and homeostatic model of insulin resistance (HOMA-IR) were calculated from the fasting measurements, and the area under the curve (AUC) and maximum percentage of change from baseline were calculated from the MMT data. Fasting insulin and triglyceride (Tg) levels were lower in the DM group compared to the PL group (Insulin: 24.4±13.7 vs. 68.0±67.2 pmol/L, p=0.003 and Tg: 168.0±107.7 vs. 1378.3±1927.3 mg/dL, p<0.001). HOMA-IR was significantly higher in the PL group compared to the DM group (6.0±2.1 vs. 3.3±1.5, p=0.005), as well as ADIPO-IR (297.0±241.1 vs. 115.3±80.1, p=0.03). NEFA, glucose and triglyceride AUC were significantly higher in the PL group compared to the DM group. Patients with PL had higher glucose and triglyceride levels throughout the MMT at all-time points. Interestingly, NEFA levels were similar in both groups at baseline, but the PL group suppressed NEFA less than DM group (54.9±13.3% vs. 69.2±11.1%, p=0.002) despite higher insulin levels. Additionally, we divided the PL group according to the presence of a pathogenic variant in the lamin A gene (n=8) versus those without mutations in this gene (n=9), but there were no notable differences among these subgroups with respect to NEFA levels at baseline or during the meal. These findings support the need to better understand and address the origins of abnormal NEFA kinetics and adipose tissue insulin resistance in PL patients.
Association of Urbanization and Lower Light Exposure With Increased Body Mass Index
Authors: Constantino Débora Barroggi , Xavier Nicoli , Roenneberg Till , Hidalgo Maria , Pilz Luísa
Published: May 2021

Introduction: Light/dark cycles are the main synchronizing signal (zeitgeber) that entrain human’s internal clock to the 24h-days. Some aspects of urban environments, including irregular light exposure and weak zeitgebers, influence the circadian organization and thereby may have an impact on metabolism. Comparing communities at different levels of urbanization and with different histories of access to electricity might provide evidence to support associations previously found between disrupted patterns of light exposure and increased populational rates of overweight and obesity. The present study aimed to investigate whether living at a higher level of urbanization would be associated with higher body mass index (BMI). It was hypothesized that BMI is higher in urbanized communities, since their inhabitants have weaker zeitgebers, often associated with disrupted circadian rhythms. Methods: We conducted a cross-sectional study in Quilombolas communities, located in the south of Brazil. Subjects were categorized into 5 groups based on their communities’ stage of urbanization and history of access to electricity: from rural with no access to electricity to highly urbanized communities that have access to the grid. We used data from 134 participants aged 16 - 92 years old (63% women), who had 7 days of light exposure recordings collected using wrist-worn actimeters. We also collected anthropometric data to calculate BMI, which was then categorized as follows: ≥18.5 kg/m² to <25 kg/m² = normal weight; ≥25 kg/m² to < 30 kg-m² = overweight; ≥ 30 kg/m² = obesity. We used Shapiro-Wilk to test for normality, Kruskal-Wallis followed by Dunn to compare BMI between groups and Spearman to assess whether there was an association between patterns of light exposure and BMI. Results: Kruskal-Wallis/Dunn test showed a significant difference in BMI between the urban group and the rural ones (KW: X² = 11.987, p < 0.001). Lower average light exposure between 7 am and 5 pm was significantly correlated with higher BMI (Spearman, r = - 0.296, p < 0.001). Also, higher average light exposure at night (from 1 am to 6 am) was significantly correlated with higher BMI (Spearman, r = 0.256, p = 0.002). Conclusions: Our results support the hypothesis that low amplitudes of light exposure may be a risk factor contributing to the high prevalence of obesity worldwide. Studies have previously shown associations between BMI and social jetlag, suggesting the correlations found in our study may be related to higher levels of circadian misalignment, more often present where zeitgeber strength is lower, as in urban environments. Future research is needed to address causal relationships between light exposure and excessive body mass in humans. Provided light exposure is a risk factor for obesity, these results point to potential new targets for intervention and prevention strategies.
Clinically-Relevant Weight Loss is Achieved Independently of Early Weight Loss Response to Once-Weekly Subcutaneous Semaglutide 2.4 MG (STEP 4)
Authors: Mosenzon Ofri , Garvey W Timothy , Hesse Dan , Koroleva Anna , Kushner Robert F , Lim Soo , Lingvay Ildiko , Wallenstein Signe O R , Wadden Thomas A , Le Roux Carel W
Published: May 2021

Background: Semaglutide, a glucagon-like peptide-1 analogue, is being investigated in people with overweight or obesity. A post-hoc analysis of the STEP 4 trial was conducted to identify whether early weight loss is predictive of later weight loss with maintenance once-weekly subcutaneous (s.c.) semaglutide 2.4 mg.

Methods: STEP 4 was a randomized, double-blind, phase 3 withdrawal trial (NCT03548987). Adults aged ≥18 years with either body mass index (BMI) ≥27 kg/m2 with ≥1 weight-related comorbidity or BMI ≥30 kg/m2, without type 2 diabetes, underwent a 20-week run-in period. Participants reaching the maintenance dose of once-weekly s.c. semaglutide 2.4 mg at week 20 (regardless of weight loss achieved) were randomized 2:1 to semaglutide 2.4 mg or placebo, as adjunct to lifestyle intervention, for an additional 48 weeks. Percent change in body weight from week 0 to 68 was estimated using a mixed model for repeated measurements analysis with treatment, week 20 responder status, and the interaction between treatment and week 20 responder status as factors, and baseline body weight as a covariate, all nested within visit (based on the trial product estimand [treatment effect assuming treatment adherence and without use of rescue intervention] for the on-treatment period). Participants were considered responders if they achieved ≥5% weight loss at week 20. Whether the week 20 response to semaglutide predicted the achievement of clinically-relevant weight loss (≥5%) by week 68 was also assessed.

Results: In STEP 4, 902 participants initiated semaglutide at week 0, of whom 803 were randomized at week 20 (semaglutide: n=535, placebo: n=268; characteristics at week 0 for all randomized participants: mean age 46 years, body weight 107.2 kg, BMI 38.4 kg/m2; 79.0% female; 83.7% white). For the 88.0% of participants randomized to semaglutide and who were responders at week 20, mean body weight change from week 0 to 68 was -19.7%. For non-responders at week 20, mean body weight change was -6.4% with continued semaglutide vs -0.3% with switch to placebo. Of all participants randomized to semaglutide, 86.2% achieved a clinically-relevant weight loss (≥5%) at week 68. Being a responder at week 20 was highly predictive of achieving this outcome (positive predictive value: 96.4%), whereas being a non-responder at week 20 had limited predictive value (negative predictive value: 42.9%).

Conclusion: In the STEP 4 trial, the vast majority of participants who were randomized to the maintenance dose of once-weekly s.c. semaglutide 2.4 mg at week 20 had lost ≥5% body weight by week 68, with most achieving this by week 20. Overall weight loss with semaglutide was greater among early responders, but non-responders also achieved a clinically-relevant weight loss by week 68 if semaglutide treatment was continued.
How Personality and Unpredictability of Resources Impact Binge Eating Symptoms in Normal Weight Subjects: A Path Analysis
Authors: Weydmann Gibson , Eckhardt Joseane , Bizarro Lisiane , Friedman Rogerio
Published: May 2021

STUDIES ASSESSING SENSITIVITY TO ENVIRONMENTAL STIMULI INDICATE THAT SUBJECTS WITH BINGE EATING DISORDER (BED) ARE MORE PRONE TO REACT TO STRESSFUL SITUATIONS, AND MORE WILLING TO PURSUE IMMEDIATE REWARDS IN COMPARISON TO SUBJECTS WITHOUT BED. UNPREDICTABILITY OF FAMILY RESOURCES RELEVANT TO CHILD DEVELOPMENT INCREASES THE CHANCES OF EXTERNALIZING BEHAVIORS IN CHILDHOOD AND, COUPLED WITH PERSONALITY PROFILES LINKED TO BED, MAY INCREASE THE ODDS OF MANIFESTING BINGE EATING (BE) IN ADULTHOOD. THIS STUDY AIMED TO INVESTIGATE WHETHER PERSONALITY AND UNPREDICTABILITY OF RESOURCES INTERACT TO PREDICT BE SYMPTOMS IN YOUNG ADULTS, EVEN BEFORE THE ONSET OF OBESITY. THE SAMPLE CONSISTED OF 257 ADULTS (AGES 20.73 ± 1.78 YEARS, MEAN ± SD), MOSTLY WHITE (N = 233), UNDERGRADUATES (N = 236), AND WITH A BMI OF 21.84 ± 1.68 KG/M². PERSONALITY WAS STUDIED USING THE BIS AND BAS SCALES THAT ASSESS, RESPECTIVELY, AVOIDANCE OF AVERSIVE STIMULI AND CONFLICT SITUATIONS, AND APPROACH TO AND DESIRE OF REWARD STIMULI. UNPREDICTABILITY OF NURTURE AND CARE, FINANCIAL RESOURCES, AND MEAL AVAILABILITY WERE ASSESSED USING THE FAMILY UNPREDICTABILITY SCALE (FU). BE SYMPTOMS WERE ASSESSED USING THE BINGE EATING SCALE (BES). A PATH ANALYSIS MODEL WAS USED TO ANALYZE THE DATA. PERSONALITY FACTORS WERE TREATED AS PRINCIPAL PREDICTORS, FU AS MEDIATORS, AND BE SYMPTOMS AS THE DEPENDENT/OUTCOME VARIABLE. GENDER, BMI, AND SOCIOECONOMIC STATUS WERE INCLUDED IN THE MODEL AS COVARIATES. AN EXCELLENT MODEL FIT WAS OBTAINED, [χ² (31) = 26.588, P = 0.692; RMSEA < 0.01; CFI = 1.000; TFI = 1.041], AND THE FINAL MODEL EXPLAINED 20.1% OF BE VARIANCE. THE POSITIVE EFFECTS OVER BE VARIANCE SUGGEST THAT FEMALE PARTICIPANTS (β = 0.180) WITH A HIGHER TENDENCY TO SEEK FOR IMMEDIATE REWARDS (BAS SUBSCALE, β = 0.205) AND AVOID CONFLICT SITUATIONS (BIS SCALE, β = 0.304), AND WITH A BMI CLOSER TO 25 KG/M² (β = 0.130) SCORED HIGHER IN BES. ONLY ONE FU FACTOR WAS RELATED TO BE, WITH MARGINAL SIGNIFICANT RESULTS (NURTURE AND CARE, β = 0.145, P = 0.056). HIGHER POSITIVE REACTIONS TO BRIEF REWARDS - ANOTHER BAS SUBSCALE - WERE NEGATIVELY (β = − 0.123) RELATED TO BE SYMPTOMS, REPRESENTING A PROTECTIVE FACTOR. THE OBSERVED EFFECTS OF PERSONALITY AND GENDER ARE CONSONANT WITH THE AFFECT REGULATION THEORY OF EATING DISORDERS, AS BE MIGHT BE AN IMPULSIVE STRATEGY TO REGULATE EMOTION IN FEMALE PATIENTS WITH GENETICALLY INFLUENCED PERSONALITY TRAITS LINKED TO STRESS VULNERABILITY AND REWARD SENSITIVITY. RESPONSIVENESS TO BRIEF REWARDS IS A PROTECTIVE FACTOR FOR DEPRESSIVE SYMPTOMS LINKED ALSO TO HEALTHY BEHAVIORS, AND IT MAY HELP PATIENTS TO PLAN AND ENGAGE IN STRATEGIES TO PREVENT BE. LONGITUDINAL MONITORING OF THESE PARTICIPANTS MAY ANSWER WHETHER PERSONALITY PROFILES IMPACT WEIGHT GAIN AND ADHERENCE TO WEIGHT REDUCTION INTERVENTIONS IN THE FUTURE.
Incidence of Insulin Resistance in Obese Adolescent of Type-2 Diabetes Mellitus Patients
Authors: Javaid Farrukh , Khurshid Rukhshan , Ashraf Huma , Mazhar Abeera , Amir Lubna
Published: May 2021

Background: Insulin resistance is a reduced response of tissue to insulin-mediated action on cells. It may be due to many reasons, including the surplus of adipose tissue, which cause a resistance of insulin. Aims and Objectives: To find the incidence of insulin resistance in obese adolescent of type-2 diabetes mellitus patients.

Material and Methods: The study involved 50 adolescents aged 14–20 years old. Adolescents with BMI > 26.0 Kg/m2 were included in the study. Levels of fasting blood sugar, Hb A1c and serum insulin were estimated. The index of Homeostatic model assessment for insulin resistance or HOMA-IR was calculated. The cut-off value of HOMA-IR was > 3.16 for both genders.

Results: It was observed that the values of BMI and level of fasting blood sugar of first degree relatives of diabetics was significantly higher as compared to their controls. Levels of both blood HbA1c and serum insulin were increased but significant difference was observed only in case of serum insulin when compared with their controls.

Conclusion: Obesity in adolescents of first degree relatives of diabetics shows a major reason of insulin resistance. The incidence of insulin resistance in obese adolescents signals a perturbing trend for the burden of type 2 diabetes in our country.
A Novel Variant of the SH2B1 Gene in an Obese Child With Type 2 Diabetes
Authors: Morillo Mariaester Makacio , Ukarapong Supamit , Seeherunvong Tossaporn
Published: May 2021

Obesity in children and adolescents is at epidemic levels in the United States and creates high risk for comorbidities later in life. Childhood obesity is thought to be the result of behavioral and nutritional problems. Although genetic factors may play a role in the etiology of obesity, monogenic forms of obesity are rare. We present a child with obesity, behavioral problems, leptin resistance, and type 2 diabetes who also carries a mutation of Sarcoma Homologous 2B adapter protein 1 (SH2B1). The subject was evaluated at 13 7/12 years old. He had polyphagia, learning disability, aggressive behavior and marked obesity. At ages 9,11, and 13 years respectively, his BMI was 9%, 16%, and 52% above the 95th percentile. At 13 7/12 years old, his height was at the 80th percentile and BMI was 66% above the 95th percentile. He had marked acanthosis nigricans and he was prepubertal. Fasting blood glucose and insulin levels were 116 mg/dl and 592 mIU/L, respectively. Hemoglobin A1c was 6.5% and metformin therapy was initiated for type 2 diabetes. Fasting leptin level (41.5 ng/mL) was markedly elevated indicating leptin resistance. DNA methylation study excluded Prader-Willi syndrome. DNA sequencing indicated a novel heterozygous c.1555G>T variant of SH2B1 gene, which is predicted to result in the amino acid substitution p. Asp519Tyr. The analysis by PolyPhen-2 and MutationTaster predicts that the variant is a pathogenic mutation affecting protein functions. SH2B1 interacts with JAK2 and may play a role in insulin signaling. Pathogenic heterozygous variants in SH2B1 have been associated with obesity, insulin resistance and maladaptive behavior phenotypes (Pearce et al, 2014). Sh2b1-null mice develop severe leptin resistance, obesity, and type 2 diabetes. Our report underscores the importance of investigating monogenic causes of obesity in subjects who present severe obesity, diabetes, and behavioral problems. Additional studies are needed to determine the association between this novel mutation and the clinical features of this patient.
The Use of Liraglutide in Obese Patients With COVID-19: A Case Report
Authors: Hanada Taliê Zanchetta Buani , Knack Rafael Silvestre , Knack Renata Silvestre
Published: May 2021

Introduction: In December 2019, a new type of coronavirus was discovered in Wuhan, China, characterized by a picture of atypical pneumonia composed of fever, dry cough and progressive dyspnea. Autopsy analyzes of patients with Covid-19 were performed, and hyperactivation of cytotoxic T cells was observed, suggesting an increase in humoral-type immunological signaling, where interleukin 6 (IL-6) is a mediator present that can fit as a potential critical agent for exacerbation of inflammatory conditions. In addition, not only interleukin-6, but also serum C-reactive protein (CRP) and ferritin have been recognized as strong predictors of COVID-19 severity. Recent studies have shown that the use of liraglutide has antioxidant and anti-inflammatory effects in vitro. Thus, the present case report discusses the possible anti-inflammatory properties of the antidiabetic drug liraglutide (Saxenda), in Covid-19. Clinical Case: JCMS, 45 years, male, married, obese grade 2 (BMI: 38.2), sought medical service on August 18, 2020, bringing a positive result of the RT-PCR test for Covid-19, performed in last day. The patient was in good general condition, reporting mild headache and adynamia. He was prescribed to start a treatment with Saxenda (6mg/ml - started 0.6mg/day at week 1, with a gradual increase up to 3mg/day at week 5); Jardiance (25mg / day); Fluimicil (600mg); Ivermectin (6mg) and Colchicine (0.5mg every 12 hours). In addition, collection of laboratory tests was requested. Examination results: IL6: <1.5 pg/mL; Ferritin: 819 ng/ml; C-reactive protein: 5.1mg/L. On August 24, the patient was tachycardic (HR 120–140 bpm) associated with headache and fever (38 °C). Azithromycin (500mg), dexamethasone (4mg) and dipyrone (1g) were prescribed. Collection of laboratory tests was requested. Examination results: IL6: 9.3 pg/mL; Ferritin: 1085 ng/ml; C-reactive protein:23.9mg/L. On September 3, the patient was in good general condition, eupneic, afebrile, with no complaints to declare. On September 6, the collection of laboratory tests was requested. Examination results: IL6: <1.5 pg/mL; Ferritin: 687 ng/ml; C-reactive protein: 1.7mg/L. Conclusion: Based on the described report, it is possible to observe a good clinical and laboratory evolution of the patient with Covid-19 who, among the drugs used, made use of liraglutida. Diabetes and obesity are considered significant risk factors for morbidity and mortality by COVID-19, since they are a condition of low-grade chronic inflammation and in these conditions, inflammatory markers such as CRP, IL-6 and ferritin have strong signs of alteration. Thus, the possible beneficial effect of the administration of liraglutide in obese patients is highlighted, as a potential anti-inflammatory effect, especially in the COVID-19 era.
Cholesterol-Free Ketogenic Diet Administration Ameliorates Experimental Metabolic Syndrome
Authors: Agosti Emanuela , Alessia Provera , Gadipudi Laila L , Ramavath Naresh N , Antonio Colasanto , Raineri Davide , Chiocchetti Annalisa , Arlorio Marco , Coisson Jean D , Caputo Marina , Reano Simone , Filigheddu Nicoletta , Albano Emanuele , Sutti Salvatore , Prodam Flavia
Published: May 2021

Background and Aims: Metabolic syndrome (MetS) is a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and dyslipidemia. The prevalence of MetS parallels the rise of obesity rate reaching pandemic proportions due to the increased consumption of high-calories-high-fat-high-carbohydrates low-fibers diet associated with a sedentary lifestyle. MetS is associated with a plethora of comorbidities as non-alcoholic fatty liver disease (NAFLD). Noteworthy, NAFLD is considered the hepatic manifestation of MetS, and it can further progress to non-alcoholic steatohepatitis (NASH) that, in its turn, can evolve to cirrhosis and hepatocellular carcinoma (HCC). Despite the clinical relevance of NAFLD/NASH, however, effective therapy is still lacking. Lifestyle changes, including diet and physical activity, are so far the most effective interventions in NAFLD. Referring to nutritional approaches, however, there is not a definitive agreement concerning the dietary regimen to introduce into clinical practice. In this study, we investigated the capacity of a cholesterol-free ketogenic diet (KD) to improve pathological parameters associated with experimental MetS. Methods: MetS was induced in C57BL/6 mice by feeding with a cholesterol-enriched western diet (WD) up to 16 weeks followed by the switching to KD for further 8 weeks. WD and KD were chemical characterized through GC and SD-PAGE analysis. Results: KD administration in MetS mice significantly improved the liver pathological manifestations by lowering the gene expression of pro-inflammatory/fibrogenetic markers such as CCl2, IL-12, CD11b, OPN, Gal-3, TGF-β and α1-procollagen. Furthermore, KD feeding decreased the hepatic content of triglycerides and the hepatocellular damage, as testified by the reduction in ALT release. These observations were further supported by the histological analyses that revealed a significant amelioration in the extent of steatosis, necro-inflammation, and collagen fibers deposition, as confirmed by the Sirius-red staining in KD-fed mice. Interestingly, KD reduced the splenomegaly observed in WD-fed mice suggesting a reduction in chronic systemic inflammation. Finally, KD feeding ameliorated WD-induced muscle atrophy as confirmed by the recovery of the gastrocnemius mass. Microbiota analyses are ongoing. Conclusion: Altogether these results suggest that cholesterol-free ketogenic diet administration might represent a potential therapeutic strategy for MetS.
Hepatic GH Receptor Signaling Directly Suppresses Hepatic Steatosis and De Novo Lipogenesis, Independent of Changes in Plasma IGF1 and Insulin
Authors: Vazquez Borrego Maria del Carmen , Moreno Mercedes del Rio , Sarmento-Cabral Andre , Mahmood Mariyah , Subbaiah Papasani V , Yakar Shoshana , Cordoba-Chacon Jose , Puchowicz Michelle , Kineman Rhonda D
Published: May 2021

A reduction in GH, as well as IGF1, is associated with non-alcoholic fatty liver disease (NAFLD). However, the relative contribution of changes in circulating GH and IGF1, to hepatic triglyceride accumulation (steatosis), remains to be clearly defined. To study the direct actions of GH on hepatocyte metabolism, we have utilized a mouse model of adult-onset, hepatocyte-specific, GHR knockdown (aHepGHRkd; 10–12 week-old, GHRfl/fl male mice, treated with AAV8-TBGp-Cre). In this and previous reports, we have observed that aHepGHRkd male mice rapidly develop steatosis (after 7 days) associated with enhanced de novo lipogenesis (DNL; measured by deuterated H2O labeling, 10h after 0800h food removal), and low ketone levels, suggestive of reduced hepatic β-oxidation. Of note, aHepGHRkd also reduces plasma IGF1 levels to >80% of GHR-intact controls (GHRfl/fl mice treated with AAV8-TBGp-Null), leading to a rise in GH, due to loss of IGF1 negative feedback to the pituitary/hypothalamus. This reciprocal shift in IGF1/GH is associated with an increase in insulin levels. Therefore, it is possible that the steatosis that develops in aHepGHRkd mice is the consequence of systemic insulin resistance supplying excess substrates (glucose and NEFA) for hepatic lipogenesis. However, inconsistent with this theory is the fact that glucose and NEFA levels are not altered after aHepGHRkd. To tease out the indirect (perhaps driven by high insulin levels) vs. direct effects of GH on hepatocyte lipid accumulation, male aHepGHRkd mice were injected with a vector expressing rat IGF1 (AAV8-TBGp-rIGF1). Reconstitution of hepatocyte IGF1 in aHepGHRkd mice, raised plasma IGF1 and normalized GH, insulin and ketone levels, but hepatic steatosis and DNL remained greater than that of GHR-intact controls, indicating GH directly suppresses hepatic fat accumulation. RNAseq analysis of livers from aHepGHRkd mice showed expression of genes related to carbohydrate metabolism (Gck, Khk) and fatty acid synthesis (Fasn, Srebf1, Usf1), processing (Scd1) and uptake (Cd36) were increased, while genes related to gluconeogenesis (Pck1, Fbp1, G6pc) were reduced. Remarkably, IGF1 reconstitution had no major impact on the hepatic transcriptome of aHepGHRkd mice, with the exception of reducing the expression of Srebf1, consistent with the reduction in circulating insulin levels. Interestingly, carbohydrate-responsive element-binding protein (CHREBP) levels, but not mRNA levels, were greater in aHepGHRkd mice with or without IGF1 reconstitution, consistent with upregulation of CHREBP target genes (Khk and Fasn among others). Taken together, these results suggest GH directly regulates steatosis, at least in part, by suppressing carbohydrate-driven DNL, where additional studies are underway to test this hypothesis.
Disruption of Estrogenic and Androgenic Bioactivities in Human Fetuses Exposed to Maternal Smoking
Authors: Talia Chiara , Budin Clémence , Panagiotis Filis , van der Burg Bart , Connolly Lisa , Fowler Paul A
Published: May 2021

Endocrine disruptors (EDs) interfere with hormonal signalling and, given that multiple developmental processes are hormone-driven, the prenatal period is a window of increased sensitivity. Maternal smoking is a real-life model of in utero exposure to a complex mixture of EDs. Cigarette smoke contains of >7,000 pollutants, including polycyclic aromatic hydrocarbons (PAHs), which are AhR ligands and cross-talk with the estrogen receptor (ER) system. Prenatal exposure to cigarette smoke is associated with adverse outcomes, including intrauterine growth restriction and increased risk of metabolic syndrome later in life. We aimed to evaluate ED effects associated with smoke exposure in human fetuses. Fetal tissues (plasma, n=48; placenta, n=30; liver, n=29) from elective terminations of normally progressing pregnancies, ranging from 10 to 20 gestation weeks, were collected (SAFeR and FEGO studies: REC 15/NS/0123, REC 04/S0802/21). PAHs and PAH-like compounds were extracted from placenta and fetal liver. Bioactivity levels in plasma, placenta and liver extracts were determined using ER and androgen receptor (AR) transactivation reporter gene assays. PAH burden was evaluated using the AhR-responsive DRhp-CALUX assay. Smoke exposure was associated with a 1.3-fold increase in plasma estrogenic activity. The developmental trajectory of androgenic activity was altered in plasma of smoke-exposed fetuses, with significant anti-androgenic activity in older fetuses (>16 weeks of gestation). In males, plasma androgenic activity was positively associated with testes weight and anogenital distance. In contrast, placentas from smoking mothers had significantly increased androgenic potential. Furthermore, AhR-like activity was 2.9-fold higher in smoke-exposed placentas compared to controls, and 2.3-fold higher in female compared to male fetal livers. Overall, all bioactivity levels were higher in placentas compared to fetal liver. Prenatal exposure to cigarette smoke is associated with higher placental AhR activation, indicative of increased xenotoxicants burden. We also report that smoke-exposed fetuses showed increased circulating estrogenic activity and disrupted androgenic potential, across 10-20 weeks of gestation, in both fetal plasma and placenta. This demonstrates that EDs present in cigarette smoke are able to interfere with hormonal signalling and alter dynamic endocrine activity profiles, which are critical to ensure appropriate, sex-specific, development. These ED effects are likely to disturb placental function and reprogramme fetal development and thus impacting on life-long health.