bluuebunny/crossref_metadata_2025 huggingface dataset:
DTPA clearance test: a sensitive method for detecting radiation-induced lung fibrosis in lung cancer patients
Authors: Keşoğlu Tok Hatice , Yetkin Nur Aleyna , Baran Ketencioglu Burcu , Tutuş Ahmet , Eroğlu Celalettin , Tutar Nuri , Oymak Fatma Sema , Gulmez İnci
Published: October 2023

Objective

The aim of this study is to analyze the frequency of lung injury and the sensitivity of the diethylenetriamine penta-acetic acid (DTPA) clearance test in detecting lung injury in patients undergoing radiotherapy (RT) to the thorax.

Material and method

Twenty individuals scheduled for RT for lung cancer were included as the patient group. The healthy control group consisted of 20 age and gender-matched individuals who were nonsmokers with no history of comorbidities. We conducted follow-up with patients at 0–1-6 months, performing carbon monoxide diffusion test (DLCO), DTPA clearance test (excluding the first month), and high-resolution computed tomography of the thorax. The control group was followed up with DLCO between the baseline and 6th months.

Results

Ninety percent of the patient group was male, and the median age was 62 years. Seventy percent of the patients had squamous cell carcinoma and adenocarcinoma. Pneumonitis was detected in the patient group in the first month (100%) and fibrosis in the sixth month (%100) Both at the beginning and in the sixth month, the DLCO values of patients who received RT were lower than those of the control group (P = 0.001 and P < 0.001, respectively). While DTPA clearance was similar between irradiated and non-radiated lungs at the beginning, there was a substantial decrease in the irradiated lung in the sixth month(P = 0.001). There was no significant correlation between malignancy type, RT dose, and tumor size(P > 0.05).

Conclusion

The DTPA clearance test could be an alternative method for demonstrating radiation injury in patients receiving RT.
Brain positron emission tomography in idiopathic normal-pressure hydrocephalus: new 18F-fluorodeoxyglucose pattern in a long-known syndrome
Authors: Cistaro Angelina , Quartuccio Natale , Piccardo Arnoldo , Meo Giuseppe , Gandoglia Ilaria , Schiera Irene Giovanna , Fania Piercarlo , Lupidi Francesco , Bottoni Gianluca , Massollo Michela , Altrinetti Vania , Pestarino Emanuela , Iacozzi Massimiliano , Iantorno Massimiliano , Del Sette Massimo
Published: October 2023

Aim

Patients with idiopathic normal-pressure hydrocephalus (iNPH) can show a global reduction in cerebral glucose metabolism at [18F]Fluorodeoxyglucose (FDG) PET. The presence of caudate hypometabolism has been identified as a potential biomarker in iNPH, yet there is limited evidence of hypermetabolic findings in patients with iNPH so far.

Methods

We retrieved retrospectively patients with iNPH and normal cognitive assessment, evaluated before surgery undergoing brain [18F]FDG-PET. The 18F-FDG-PET brain scans were compared to those of a control group of healthy subjects, matched for age and sex, by statistical parametric mapping (SPM) to identify areas of relative hypo- and hypermetabolism. Furthermore, the existence of a correlation between areas of hypo- and hypermetabolism in the patient group was tested.

Results

Seven iNPH patients (mean age 74 ± 6 years) were found in the hospital database. SPM group analysis revealed clusters of significant hypometabolism (P = 0.001) in the iNPH group in the dorsal striatum, involving caudate and putamen bilaterally. Clusters of significant hypermetabolism (P = 0.001) were revealed in the bilateral superior and precentral frontal gyrus (BA 4, 6). A significant inverse correlation between striatal hypometabolism and bilateral superior and precentral frontal gyrus hypermetabolism was revealed (P < 0.001 corrected for multiple comparisons).

Conclusion

In this cohort, patients with iNPH showed subcortical hypometabolism, including bilateral dorsal striatum. To the best of our knowledge, this is the first report demonstrating a hypermetabolic pattern in the primary motor and premotor areas, and showing an inverse correlation between the striatum and motor cortex in patients with iNPH.
A practical approach to caring for atopic dermatitis in children
Authors: Bayer Diana K.
Published: October 2023

Purpose of review

Atopic dermatitis is a chronic, systemic disease with primary cutaneous clinical manifestations and is commonly attributed to an exaggerated Th2 inflammatory response. Recent research regarding risk factors, prevention, clinical features, and management of atopic dermatitis will be reviewed.

Recent findings

In the last decade, advances have been made in identifying the factors that either confer increased risk for or protection from atopic dermatitis and associated atopy. Progress has also been made in the clinical management of this disease. Promising biomarkers and therapeutically informative characteristics of this disease have been identified in young children with and without the presence of eczema, but much has yet to be elucidated. Progress has also been made in clarifying the advantages and disadvantages of respective medical managements, including but not limited to topical corticosteroids, topical calcineurin inhibitors, phototherapy, systemic immunosuppressants, and targeted immunotherapy. Given that medical management may show variable efficacy in a child, an optimized skin care regimen is of utmost importance as well.

Atopic dermatitis is a challenging, chronic systemic disease that incurs significant morbidity in affected children. Although management options have been somewhat disappointing in years past, promising results have been observed in recent advances in targeted immunotherapy.
Probiotic Supplementation for Promotion of Growth in Undernourished Children: A Systematic Review and Meta-Analysis
Authors: Imdad Aamer , Pandit Natasha G. , Ehrlich Julie M. , Catania Joseph , Zaman Muizz , Smith Abigail , Tanner-Smith Emily E. , Zackular Joseph P. , Bhutta Zulfiqar A.
Published: October 2023

Objectives:

Probiotic supplementation has been proposed as a therapeutic intervention to improve growth outcomes in children with undernutrition. The objective of this review is to synthesize the current evidence on probiotic supplementation for promotion of growth in undernourished children.

Methods:

We searched MEDLINE, Cochrane CENTRAL, CINAHL, Embase, LILACS, and Scopus for randomized controlled trials (RCTs) that administered probiotics or eligible comparators to undernourished children below 5 years of age. Our primary outcomes of interest were weight-for-age, height-for-age, and weight-for-height at the longest follow-up points reported. Random-effects meta-analysis was used to calculate standardized mean differences (SMD) for continuous outcomes and risk ratios for dichotomous outcomes. The Grading of Recommendations Assessment, Development and Evaluation criteria were used to assess certainty of the evidence.

Results:

Nine RCTs with 5295 children in total were included. Durations of treatment ranged from 1 month to 1 year. Pooled analyses from 7 studies showed that probiotics may have little to no effect on weight-for-age (SMD 0.05 standard deviation [SD], 95% CI: −0.04 to 0.13, n = 2115 children; low-certainty evidence) and height-for-age (SMD −0.04 SD, 95% CI: −0.14 to 0.07, n = 1357 children; low-certainty evidence). The evidence was very uncertain about the effect on weight-for-height.

Conclusions:

Probiotics may have little to no effect on anthropometry in undernourished children, though there is considerable heterogeneity among the trials reviewed thus far. The interaction between gut microbiota and human nutrition is complex, and further research is needed to determine how the gut microbiome may contribute to undernutrition and how probiotics may affect growth in this vulnerable population.
Percutaneous Transcatheter Retrieval of Central Venous Port Fragments in Pediatric Patients; A Single-center Experience From the Pediatric Cardiology Department
Authors: Duman Derya , Aykan Hayrettin Hakan , Ertuğrul İlker , Ardiçli Burak , Aypar Ebru , Alehan Dursun , Karagöz Tevfik
Published: October 2023

Background:

Split/fracture and embolization of central venous/shunt catheters are rare but serious complications in children. Percutaneous retrieval of intravascular foreign bodies is an important minimal invasive treatment. This study is aimed to represent our largest pediatric sample experience till now of 17 years from a single institution. Another aim is to compare the results regarding the removal or leaving in place of embolized or ruptured intravascular or cardiac venous catheter parts in children.

Patients and Methods:

A total of 26 cases were included in this study. Any pediatric patient with normal coagulation parameters and a fractured catheter fragment was included in this study. Other intravascular foreign bodies related to interventional devices and/or pacemaker/implantable cardiac defibrillator leads were excluded from this study.

Results:

Twenty-six patients, of whom 25 had oncologic diseases and 1 had a ventriculoatrial shunt, were included. The median age was 83.5 months (between 20 mo and 18 y) at treatment.

Superior vena cava (9 cases), followed by the right atrium (5 cases), were the most two common sites of embolization for cardiovascular foreign bodies. The success rate of percutaneous retrieval was 92.3% in all patients. There were neither complications nor deaths. The retrieval technique revealed a predisposition for extraction through the femoral vein (96.1%) and using snare techniques (100%). Additional catheters like pigtail, National Institutes of Health, or ablation catheters were used for stabilization in selective cases in which the permanent central venous fragments stuck to the vessels. A tractional maneuver and capturing the ruptured material in the middle were other trick points for successful retrieval. Patients were asymptomatic in 76.9% of cases (20/26).

Conclusion:

Percutaneous retrieval of cardiovascular foreign bodies is a reasonable, safe, and effective way in children when the catheter fragments are free and mobile. It should be considered the preferred treatment option instead of surgery. In patients where catheter fragments are stuck and are adherent to vessels, it could be left, and followed up by anticoagulation. Novel techniques accompanied by an experienced team could be helpful in difficult cases.
Vitamin D Status in Children With High-risk Neuroblastoma
Authors: Izurieta-Pacheco Ana Carolina , Sangrós-Gimenez Ana , Martínez-Garcia Esther , Perez-Jaume Sara , Mora Jaume , Gorostegui-Obanos Maite
Published: October 2023

Background:

Vitamin D deficiency has become a matter of concern in pediatric cancer patients. A relationship between neuroblastoma and Vitamin D signaling pathways has been revealed with interest in the antiproliferative and antiinvasive properties of vitamin D. Our aim is to describe the prevalence of Vitamin D deficiency among children with high-risk neuroblastoma (HR-NB) and to explore its association with disease status.

Materials and Methods:

In all, 182 patients with HR-NB were managed at our center from 2017 to 2021. Serum 25(OH)D levels were tested at the first blood analysis performed and correlated with clinical data and disease status.

Results:

One hundred forty-eight (81.4%) had low 25(OH)D levels (48.4% categorized as deficiency (25(OH)D below 20 ng/mL) and 33.0% as insufficiency (25(OH)D 20 to 30 ng/mL). Median Vitamin D level was 20.2 ng/mL. Vitamin D levels were not associated with race or sex. Although malnourished patients had lower median 25(OH)D levels(11.1 ng/mL), no statistical association was observed with Vitamin D deficiency. There was no association between Vitamin D levels and disease status. An inverse correlation was found between age and vitamin D levels (P=0.0040).

Conclusion:

A concerning high prevalence of low Vitamin D levels affects more than two-thirds of patients with HR-NB in our cohort, regardless of the disease status at the time of evaluation. Older children are at a higher risk for deficient levels of vitamin D.
Radiolucent foreign body leading to complete small bowel obstruction: a diagnostic dilemma – a case report
Authors: Yadav Krishna K. , Ghimire Ranjeet , Subedi Sudan , Kandel Krishna , Yadav Rupesh K. , Ghimire Bikal , Shah Jayant K.
Published: October 2023

Introduction and importance:

Foreign body ingestion leading to luminal obstruction in both the small and large bowels is rare, especially in children. The authors present a case of a 7-year-old patient who presented with a small bowel obstruction caused by an ingested radiolucent foreign body. The previous herniotomy surgery 1 year back led to initial diagnostic confusion, highlighting the need for a broad differential diagnosis.

Case presentation:

A 7-year-old child with a history of herniotomy presented with symptoms of small bowel obstruction. Radiological imaging revealed a soft tissue mass mimicking a polyp or cystic lesion. During exploratory laparotomy, a cystic structure was discovered in the terminal ileum. The foreign body, identified as a fluid-filled balloon, was inaccessible to endoscopy and was gently maneuvered into the ascending colon. It was punctured and removed during on-table colonoscopy.

Clinical discussion:

This case underscores the challenges of diagnosing and managing luminal obstruction caused by radiolucent foreign bodies in children. The presence of previous surgery can mislead clinicians, necessitating a broad differential diagnosis. Radiological imaging played a crucial role in identifying the foreign body. Surgical intervention guided by an on-table colonoscopy allowed successful removal.

Conclusion:

Foreign body ingestion leading to luminal obstruction should be considered, even in cases with previous abdominal surgery. Radiological imaging aids in identification, and timely surgical intervention, guided by on-table colonoscopy, facilitates foreign body removal. Awareness of such cases is essential for optimal care in pediatric patients with luminal obstruction caused by foreign body ingestion.
Student Peer Review and Receptiveness to Feedback in Global Classrooms
Authors: Tornwall Joni , Ikonen Riikka
Published: October 2023

Background:

Development of skills in peer-to-peer feedback in multicultural and global contexts is important to excellent teaching practice in nursing education.

Purpose:

This study identified student attitudes toward giving and receiving peer-to-peer feedback between international peers in a graduate-level online instructional design course.

Methods:

Twenty-one graduate nursing students in 2 nurse educator programs from the United States and Finland participated in this descriptive study. Pre- and postcourse Feedback Orientation Scale (FOS) scores were analyzed in combination with student reflections on learning experiences related to peer-review course activities.

Results:

Mean pre- to postcourse overall FOS scores increased, suggesting greater student receptiveness to peer feedback, particularly in the dimensions of utility and self-efficacy. Postcourse reflections demonstrated increased appreciation for opportunities to triangulate feedback from multiple, diverse sources.

Conclusions:

Opportunities for graduate students in nurse educator programs to exchange peer-to-peer feedback with international peers foster growth in positive attitudes toward receiving and using peer feedback.
Evaluation of phenobarbital for prevention of alcohol withdrawal in trauma patients
Authors: Kip Lindsey Marie , Forni Allison , Dorfman Jon David , Li Irene
Published: October 2023

BACKGROUND

Up to 30% of trauma patients experience alcohol withdrawal syndrome (AWS) during their hospital admission, which is associated with worse outcomes. While benzodiazepines and phenobarbital are the mainstay of AWS management, there are limited data on the prevention of AWS. The objective was to evaluate the safety and efficacy of phenobarbital for the prevention of AWS.

METHODS

Adult patients admitted to a level 1 trauma center who received at least one dose of phenobarbital for the prevention of AWS between January 2019 and August 2021 were included. Patients were case matched to a control group managed with symptom-triggered therapy based on risk of AWS. Risk factors included sex, age, history of AWS/delirium tremens or withdrawal seizures, selected laboratory values, and screening questionnaires. The primary endpoint was the need for rescue therapy. Secondary endpoints included the time to rescue therapy, intensive care unit (ICU) length of stay (LOS), and hospital LOS.

RESULTS

Overall, 110 patients were included with 55 patients in each group. The phenobarbital group had higher baseline Injury Severity Scores (p = 0.03) and were more likely to be admitted to the ICU (44% vs. 24%; p = 0.03). The phenobarbital group required less rescue therapy (16% vs. 62%; p < 0.001) with a longer time to rescue therapy administration (26 vs. 11 hours; p = 0.01). The phenobarbital group had a longer hospital LOS (216 vs. 87 hours; p = 0.0001) but no difference in ICU LOS (p = 0.36). There was no incidence of delirium tremens or seizures and no difference in intubation rates (p = 0.68). There was no incidence of hypotension associated with phenobarbital.

CONCLUSION

Patients managed with phenobarbital had a lower need for rescue therapy for AWS with no increased adverse effects. Further studies should evaluate a protocol to prevent alcohol withdrawal in the trauma population.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Reclaiming the management of common duct stones in acute care surgery
Authors: Bosley Maggie E. , Ganapathy Aravindh S. , Sanin Gloria D. , Cambronero Gabriel E. , Neff Lucas P. , Syriani Fadi A. , Gaffley Michaela W. , Evangelista Meagan E. , Westcott Carl J. , Miller Preston R. , Nunn Andrew M.
Published: October 2023

BACKGROUND

Acute care surgery (ACS) is well positioned to manage choledocholithiasis at the time of laparoscopic cholecystectomy, but barriers to laparoscopic common bile duct exploration (LCBDE) include experience and the perceived need for specialized equipment. The technical complexity of this pathway is generally seen as challenging. As such, LCBDE is historically relegated to the “enthusiast.” However, a simplified, effective LCBDE technique as part of a “surgery first” strategy could drive wider adoption in the specialty most often managing these patients. To determine efficacy and safety, we sought to compare our initial ACS-driven experience with a simple, fluoroscopy-guided, catheter-based LCBDE approach during laparoscopic cholecystectomy (LC) to LC with endoscopic retrograde cholangiopancreatography (ERCP).

METHODS

We reviewed ACS patients who underwent LCBDE or LC + ERCP (pre−/postoperative) at a tertiary care center in the 4 years since starting this surgery first approach. Demographics, outcomes, and length of stay (LOS) were compared on an intention to treat basis. Laparoscopic common bile duct exploration was performed via using wire/catheter Seldinger techniques under fluoroscopic guidance with flushing or balloon dilation of the sphincter as needed. Our primary outcomes were LOS and successful duct clearance.

RESULTS

One hundred eighty patients were treated for choledocholithiasis with 71 undergoing LCBDE. The success rate of catheter-based LCBDE was 70.4%. Length of stay was significantly reduced for the LCBDE group compared with the LC + ERCP group (48.8 vs. 84.3 hours, p < 0.01). Of note, there were no intraoperative or postoperative complications in the LCBDE group.

CONCLUSION

A simplified catheter-based approach to LCBDE is safe and associated with decreased LOS when compared with LC + ERCP. This simplified step-up approach may help facilitate wider LCBDE utilization by ACS providers who are well positioned for a timely surgery first approach in the management of uncomplicated choledocholithiasis.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Regulatory B Cells in Solid Organ Transplantation: From Immune Monitoring to Immunotherapy
Authors: Elias Charbel , Chen Chuxiao , Cherukuri Aravind
Published: October 2023

Regulatory B cells (Breg) modulate the immune response in diverse disease settings including transplantation. Despite the lack of a specific phenotypic marker or transcription factor, their significance in transplantation is underscored by their ability to prolong experimental allograft survival, the possibility for their clinical use as immune monitoring tools, and the exciting prospect for them to form the basis for cell therapy. Interleukin (IL)-10 expression remains the most widely used marker for Breg. Several Breg subsets with distinct phenotypes that express this “signature Breg cytokine” have been described in mice and humans. Although T-cell immunoglobulin and mucin family-1 is the most inclusive and functional marker that accounts for murine Breg with disparate mechanisms of action, the significance of T-cell immunoglobulin and mucin family-1 as a marker for Breg in humans still needs to be explored. Although the primary focus of this review is the role of Breg in clinical transplantation, the net modulatory effect of B cells on the immune response and clinical outcomes is the result of the balancing functions of both Breg and effector B cells. Supporting this notion, B-cell IL-10/tumor necrosis factor α ratio is shown to predict immunologic reactivity and clinical outcomes in kidney and liver transplantation. Assessment of Breg:B effector balance using their IL-10/tumor necrosis factor α ratio may identify patients that require more immunosuppression and provide mechanistic insights into potential therapies. In summary, current advances in our understanding of murine and human Breg will pave way for future definitive clinical studies aiming to test them for immune monitoring and as therapeutic targets.
Exploring the intersection of autism spectrum disorder and eating disorders: understanding the unique challenges and treatment considerations for autistic women with eating disorders
Authors: Schröder Sabrina S. , Danner Unna N. , Spek Annelies A. , van Elburg Annemarie A.
Published: October 2023

Purpose of review

Autistic women struggle with high levels of both autistic eating behaviours and disordered eating behaviours, which might make them particularly vulnerable to develop eating disorders. Research investigating the presence and characteristics of eating disorders in autistic women is however limited, as is research examining the role of autism in the treatment and recovery of an eating disorder in autistic women.

Recent findings

The link between autism and eating disorders has mainly been investigated from the field of eating disorder research, with studies finding an overrepresentation of autism or autistic traits in eating disorders populations. Findings also suggest that autism or autistic traits are associated with a more serious presentation of the eating disorders, including a higher chance of a chronic course of the eating disorders. Most studies however lack comprehensive autism assessments, making it difficult to determine the actual prevalence of autism and its role in women with eating disorders.

Autistic women with an eating disorder seem to suffer from more complex eating disorders and seem to not benefit from current treatment modalities. This could be partly related to specific autism characteristics such as sensory sensitivities, which are not being considered by current treatment protocols. Future research needs to shed light on what underlies the eating behaviours of autistic women with an eating disorder, in order to help to adapt current treatment modalities to meet the unique needs of these women.
Neuronal activity and reward processing in relation to binge eating
Authors: Vrieze Elske , Leenaerts Nicolas
Published: October 2023

Purpose of review

Studies increasingly show the importance of reward processing in binge eating and provide evidence of associated changes in the neurobiological reward system. This review gives an up-to-date overview of the neurobiological substrates of reward processing subconstructs in binge eating. Neural findings are linked to different behavioral theories and the clinical relevance is discussed.

Recent findings

Increased neural responses in the orbitofrontal cortex, anterior cingulate cortex as well as striatum during anticipation and receipt of food rewards are found in association to binge eating. Increased model-free learning is also found and associated with altered brain reward reactivity. Data in rest report reduced striatal dopamine release and lower frontostriatal connectivity. Mechanisms of onset of binge eating are less clear, but specific personality traits, related to frontostriatal dysconnectivity, probably increase the risk of binge eating onset.

Both structural and task-based imaging studies show differences in the neurobiological reward system in binge eating. These changes are linked to specific reward processing, such as altered reward responsiveness to food cues, reinforcement learning, and habitual behavior. Findings are lined with different behavioral theories of binge eating, and a staging model is described, from onset to full illness development. Understanding the specific underlying aberrant reward mechanism in binge eating, associated with different stages of the illness, enables caregivers to focus their treatment more precisely.
Differentiating the third generation of antipsychotics: a focus on lumateperone’s similarities and differences
Authors: Munayco Maldonado Gloria M. , Schwartz Thomas L.
Published: October 2023

The development of atypical antipsychotics has evolved to include newer pharmacodynamic properties. Lumateperone, aripiprazole, brexpiprazole, and cariprazine are all dopamine-2 receptor partial agonists with varying receptor affinities. This review aims to compare the clinical and pharmacodynamic differences among these four atypical antipsychotics, all of which are unique when compared to first- and second-generation antipsychotics. For consideration is further delineating these agents as being third-generation antipsychotics. PubMed searches were conducted to compile preclinical and clinical studies derived from animal models and human subjects. Information gathered included pharmacological mechanisms, clinical efficacy, future-oriented clinical approaches, and adverse effects. Efficacy for the shared indications of these drugs seems comparable. Differences among these drugs lie more in their adverse effect profiles. For example, lumateperone was found to have the lowest rate of weight gain while brexpiprazole was found to have the highest rate of weight gain associated with increased appetite. Aripiprazole had the lowest rates of extrapyramidal symptoms not including akathisia while cariprazine had the highest. All four agents reviewed have a variety of receptor affinities, which likely generates a variety of different adverse effects. This suggests that in any given patient, clinicians may see differential clinical effects.
Mental health in patients affected by atopic dermatitis: which effects of treatment with dupilumab?
Authors: Ferrucci Silvia Mariel , Tavecchio Simona , Nicolini Gregorio , Angileri Luisa , Ceresa Alessandro , Del Tordello Giulia , Berti Emilio , Marzano Angelo Valerio , Buoli Massimiliano
Published: October 2023

Atopic dermatitis (AD) is an inflammatory skin disease. Patients with AD are prone to develop anxiety and mood disorders. Aim of this study is to investigate if treatment with dupilumab may improve mental health status of patients affected by AD.

A total of 66 patients with severe AD were included: 24 subjects were candidate or have just started (one month) treatment with dupilumab, and 42 have been in treatment for one year.

25.8%, 30.3%, and 45.5% of the total sample showed, respectively, clinically significant anxiety, depression, and symptoms of Internet addiction. Patients with anxiety symptoms resulted to have more severe AD, more sleep problems (P = 0.028), less quality of life (P = 0.001), more severe depressive symptoms (P < 0.001), to be more frequently women (P = 0.016), to be less frequently treated with dupilumab for one year (P = 0.025). Similarly, patients with clinically significant depressive symptoms resulted to have more severe AD, more sleep problems (P = 0.003), less quality of life (P < 0.001), more severe anxiety symptoms (P < 0.001), to be less frequently treated with dupilumab for one year (P = 0.008).

Patients with AD treated for one year with dupilumab showed a better mental health profile in terms of less severe anxiety and depression with respect to their counterparts.
Elevated liver transaminases among patients with psychiatric disorders
Authors: Ali Eman , Abdel Maksoud Mona Ahmed , Arafa Shaymaa M , Ibrahim Doaa , Hassan Ahmed El-Sayed , Awwad Omnia , Elbeltagy Ahmed M. , Elmahdi Essam , Elgarhi Reham , Embaby Ahmed
Published: October 2023

Hepatocyte injury is assessed by serum aspartate transaminase and alanine transaminase estimation. In psychiatric populations, antipsychotic drugs (AD) are culprit in hepatic dysfunction. To assess transaminitis among psychiatric patients treated by AD. This cross-sectional study was conducted in Zagazig University Hospitals in Egypt, from December 2022 to February 2023. A total of 135 adult patients aged ≥ 18 years, were diagnosed with psychiatric disorders after exclusion of patients receiving any hepatotoxic drugs, viral hepatitis, having chronic liver or kidney diseases, diabetes mellitus, mental retardation, and pregnant females. Among the 135 patients, 104 (77.0%) were males. Their age was 32 ± 9, The most popular used class of AD was atypical AD 84 (62.2%). The overall incidence of transaminitis among patients receiving AD was 23/135 (17.04%) of patients; 13 (56.5%) were on atypical AD compared to 10 (43.5%) patients receiving combined AD, without any statistically significant difference. The use of AD in patients with psychiatric disorders is potentially safe with minimal transaminitis (<one-fold elevation). However, baseline and regular monitoring of serum aminotransferase is recommended during treatment.
Sociodemographic and clinical factors associated with prescription of first- versus second-generation long-acting antipsychotics in incarcerated adult males
Authors: Capuzzi Enrico , Di Forti Carla Laura , Caldiroli Alice , Cova Francesca , Surace Teresa , Buoli Massimiliano , Clerici Massimo
Published: October 2023

Information on patterns of prescription of long-acting injection (LAI) antipsychotics among people who are incarcerated is lacking. Therefore, we aimed to evaluate prescribing rates for first-generation antipsychotic (FGA)-LAI versus second-generation antipsychotic (SGA)-LAI and to identify the factors associated with the prescription of one of the two classes of LAI. A cross-sectional study was conducted among incarcerated adult males hosted in Monza detention center between January 2013 and April 2023. Socio-demographic and clinical data were retrospectively collected. Descriptive and univariate statistics as well as logistic regression analyses were performed. Data were available for 135 consecutive incarcerated adult males with different mental disorders who received a LAI as part of their treatment. 75.6% of our sample was treated with FGA-LAIs, with haloperidol as the most commonly prescribed drug, followed by zuclopentixol and aripiprazole. Diagnosis of bipolar disorder and concomitant administration of antidepressants were statistically significant predictors of SGA-LAI prescription. Some patients’ characteristics may influence prescription patterns in prison. Further longitudinal studies with larger samples should confirm these findings.
The relationship between mobile phone addiction and depression, anxiety, and sleep quality in medical students
Authors: Nahidi Mahsa , Ahmadi Motahareh , Fayyazi Bordbar Mohammad Reza , Morovatdar Negar , Khadem-Rezayian Majid , Abdolalizadeh Adeleh
Published: October 2023

This study investigates the prevalence of mobile phone addiction among medical students and its relationship with depression, anxiety, and sleep quality. The study was conducted at Mashhad University of Medical Sciences from 2019 to 2021, and it included medical students at four different levels of training. Participants were selected using a stratified random sampling method. All subjects completed the Mobile Phone Addiction Scale, Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory, and Beck Anxiety Inventory through online electronic self-report questionnaires. Overall, 355 medical students were included in the study, with 203 (57.2%) being female. Mild and severe mobile phone addiction was reported by 83.7 and 2.5% of the students, respectively. Furthermore, the study’s findings revealed significantly higher sleep quality disorder, depression, and anxiety scores among students with severe mobile phone addiction compared to other participants (P < 0.001, P = 0.007, and P < 0.001, respectively). Although mobile phone addiction was prevalent, severe addiction was rare among medical students. Nevertheless, severe addiction was associated with an increased prevalence of mental health problems and sleep disturbances, emphasizing the importance of interventions aimed at reducing mobile phone addiction and improving mental health.
Characterization of baseline and longitudinal DNA Methylation in patients with sporadic Parkinsons disease
Authors: Gonzalez-Latapi Paulina , Bustos Bernabe I , Dong Siyuan , Lubbe Steven , Simuni Tanya , Krainc Dimitri
Published: October 2023

Parkinson Disease (PD) prevalence is expected to double by 2040. Presently, it appears that the complex interplay between genetic and environmental factors underlies the pathogenesis of PD. Some of the features of PD risk may be reflected in the epigenome, which serves as an interface between genetic and environmental risk factors. DNA methylation (DNAm) is the most widely studied epigenetic phenomenon. As such, there is growing interest in exploring the role of DNAm in PD. Using data from the Parkinson Progression Markers Initiative (PPMI), we characterized cross-sectional and longitudinal DNAm differences between individuals with sporadic (i.e., non-genetic) PD and healthy controls (HC). This analysis revealed 81,604 differentially methylated positions (DMPs) and 5,281 differentially methylated regions (DMRs) between sPD and HC. Gene ontology analysis revealed that these DMPs/DMRs were associated with genes involved in diverse cellular processes, including several with specific functions in the brain ("Focal adhesion", "Cholinergic synapse", "Glutamatergic synapse", "Dopaminergic synapse"). Integration of both differentially methylated sites and expressed genes showed 20 genes that were hypomethylated and overexpressed and one gene, CTSH that was hypermethylated and associated with reduced expression. Our study provides evidence that alterations in the methylome in PD are discernible in blood, evolve over time, and reflect cellular processes linked to ongoing neurodegeneration. These findings lend support to the potential of blood DNA methylation as an epigenetic biomarker for PD. To fully comprehend DNA methylation changes throughout the progression of PD, additional profiling at longer intervals and during the prodromal stage will be necessary.
Subarachnoid Hemorrhage Trials: Cutting, Sliding, or Keeping mRS Scores and WFNS Grades
Authors: Mistry Akshitkumar M. , Saver Jeffrey , Mack William , Kamel Hooman , Elm Jordan , Beall Jonathan
Published: October 2023

Rigorous evidence generation with randomized controlled trials (RCTs) has lagged for aneurysmal subarachnoid hemorrhage (SAH) compared to other forms of acute stroke. Besides its lower incidence compared to other stroke subtypes, the presentation and outcome of SAH patients also differ. This must be considered and adjusted for in designing pivotal RCTs of SAH patients. Here, we show the effect of the unique expected distribution of the SAH severity at presentation (World Federation of Neurological Surgeons, WFNS, grade) on the outcome most used in pivotal stroke RCTs (modified Rankin Scale, mRS) and consequently on the sample size. Further, we discuss the advantages and disadvantages of different options to analyze the outcome and control the expected distribution of WFNS grades in addition to showing their effects on the sample size. Last, we offer methods that investigators can adapt to more precisely understand the effect of common mRS analysis methods and trial eligibility pertaining to the WFNS grade in designing their large-scale SAH RCTs.

Purpose

The generation of rigorous evidence to inform the management of patients with aneurysmal subarachnoid hemorrhage (SAH) has lagged other types of acute strokes. The reason for this lag is multifactorial—one being that SAH has the lowest incidence of all forms of stroke. However, the paucity of SAH randomized controlled trials (RCTs) can also be self-exacerbating. Rather than adopting existing trial designs and biostatistical methods, it forces new investigators to craft these anew. Here, we provide a basic biostatistical guide for investigators to navigate two foundational dilemmas in designing large-scale SAH RCTs.
Evaluation of tooth sensitivity after scaling and root planing treated with photobiomodulation: a randomized controlled split-mouth double-blind clinical protocol
Authors: García Olazabal María Victoria , Pascuali Moya Luis Eduardo , Consolandich Cirisola Rolf Wilhem , Sobral Ana Paula Taboada , Bruno Laura Hermida , Safi Federico Todeschini , Longo Priscila Larcher , Chavantes Maria Cristina , Navarro Ricardo Scarparo , Duran Cinthya Cosme Gutierrez , Fernandes Kristianne Porta Santos , Mesquita Ferrari Raquel Agnelli , Bussadori Sandra Kalil , Motta Lara Jansiski , Horliana Anna Carolina Ratto Tempestini
Published: October 2023

It is well known that hypersensitivity affects patients recently treated with scaling and root planing. Some studies have demonstrated that photobiomodulation (PBM) can alleviate dentinal hypersensitivity by modulating pain. However, to date, there is no established protocol for its application after scaling and root planning. To evaluate tooth hypersensibility after photobiomodulation in sensitive scaling and root planning treated teeth. Study design: Randomized, controlled, double-blind split-mouth clinical trial. Methods: Forty-four patients with dentin sensibility after non-surgical scaling and root planning (SRP) will be randomly included in 2 groups: Experimental Group: SRP+ Photobiomodulation (PBM) (660nm, 100W, area 0,5cm2, 200w/cm2, 30 seconds, 3 J, 6J/cm2) and Control Group: Scaling and root planning +FBM simulation. After 7 days of scaling and root planning, all patients will be evaluated for hypersensibility. The cutoff of VAS will be 3. These patients will be included in the study. The primary outcome of the study will be the assessment of dentin hypersensitivity after 7 days of RAR measured with the visual analog scale (VAS). Also, it will be assessed the impact of oral health on the participant’s quality of life, with the OHIP-14 questionnaire. The use of analgesics (paracetamol) will be prescribed as needed and the amount of medication will be calculated. These outcomes will be evaluated after 7 days and 1 month of application. If the data are normal, they will be submitted to the ANOVA test – one way. Data will be presented as means ± SD and the p-value will be set to < 0.05.
Local Thermal Adaptation occurs via Modulation of Mitochondrial Activity in Chinook Salmon
Authors: Dimos Bradford , Lopez Alex , Schulte Patricia , Phelps Michael
Published: October 2023

Freshwater and anadromous fish have been identified as one of the most at-risk groups threatened by climate induced warming given their metabolic dependence on environmental temperature and limited ability to track favorable environmental conditions. The future of these fish will depend on their ability to adapt to new thermal regimes over biologically relevant timescales. However, the mechanistic understanding of temperature responses required to predict if adaption can keep pace with climate change is limited. To address this question, we investigated the mechanistic basis of thermal adaptation across multiple levels of biological organization in the iconic and endangered Chinook Salmon (Oncorhynchus tshawytscha). We uncovered a mechanistic basis of thermal adaptation centered on the thermal responsiveness of mitochondrial function which modulates the extent to which rising temperatures increase metabolic demand on the cardio-respiratory system. These insights demonstrate that the populations studied here are able to maintain high levels of physiological performance at temperatures several degrees above historic averages, indicating that the decline Chinook Salmon and failure to recover despite conservation efforts is unlikely to be due to increased temperatures as a consequence of climate change.
Convergent evolution of ventral adaptations for enrollment in trilobites and extant euarthropods
Authors: Losso Sarah R. , Affatato Pauline , Nanglu Karma , Ortega-Hernández Javier
Published: October 2023

The ability to enroll for protection is an effective defensive strategy that has convergently evolved multiple times in disparate animal groups ranging from euarthropods to mammals. Enrollment is an evolutionary staple of trilobites, and their biomineralized dorsal exoskeleton offers a versatile substrate for the evolution of interlocking devices. However, it is unknown whether trilobites also featured ventral adaptations for enrolment. Here, we report ventral exoskeletal adaptations that facilitate enrollment in exceptionally preserved trilobites from the Upper Ordovician Walcott-Rust Quarry in New York State, USA. Walcott-Rust trilobites reveal the intricate three-dimensional organization of the non-biomineralized ventral anatomy preserved as calcite casts, including the spatial relationship between the articulated sternites (i.e., ventral exoskeletal plates) and the wedge-shaped protopodites. Enrollment in trilobites is achieved by ventrally dipping the anterior margin of the sternites during trunk flexure, facilitated by the presence of flexible membranes, and the close coupling of the wedge-shaped protopodites. Comparisons with the ventral morphology of extant glomerid millipedes and terrestrial isopods reveal similar mechanisms used for enrollment. The wedge-shaped protopodites of trilobites closely resemble the gnathobasic coxa/protopodite of extant horseshoe crabs. We propose that the trilobites’ wedge-shaped protopodite simultaneously facilitates tight enrollment and gnathobasic feeding with the trunk appendages.
ONECUT2 Activates Diverse Resistance Drivers of Androgen Receptor-Independent Heterogeneity in Prostate Cancer
Authors: Qian Chen , Yang Qian , Rotinen Mirja , Huang Rongrong , Kim Hyoyoung , Gallent Brad , Yan Yiwu , Cadaneanu Radu M. , Zhang Baohui , Kaochar Salma , Freedland Stephen J. , Posadas Edwin M. , Ellis Leigh , Di Vizio Dolores , Morrissey Colm , Nelson Peter S. , Brady Lauren , Murali Ramachandran , Campbell Moray J. , Yang Wei , Knudsen Beatrice S. , Mostaghel Elahe A. , Ye Huihui , Garraway Isla P. , You Sungyong , Freeman Michael R.
Published: October 2023

Significance Statement

ONECUT2 (OC2) is a master transcription factor that alters lineage identity by activating gene networks associated with both neuroendocrine prostate cancer and prostate adenocarcinoma. A small molecule inhibitor of OC2 represses the lineage plasticity program activated by enzalutamide, suggesting OC2 inhibition as a novel therapeutic strategy to prevent emergence of treatment-resistant variants.

Graphic Abstract

Androgen receptor-(AR-) indifference is a mechanism of resistance to hormonal therapy in prostate cancer (PC). Here we demonstrate that the HOX/CUT transcription factor ONECUT2 (OC2) activates resistance through multiple drivers associated with adenocarcinoma, stem-like and neuroendocrine (NE) variants. Direct OC2 targets include the glucocorticoid receptor and the NE splicing factorSRRM4, among others. OC2 regulates gene expression by promoter binding, enhancement of chromatin accessibility, and formation of novel super-enhancers. OC2 also activates glucuronidation genes that irreversibly disable androgen, thereby evoking phenotypic heterogeneity indirectly by hormone depletion. Pharmacologic inhibition of OC2 suppresses lineage plasticity reprogramming induced by the AR signaling inhibitor enzalutamide. These results demonstrate that OC2 activation promotes a range of drug resistance mechanisms associated with treatment-emergent lineage variation in PC. Our findings support enhanced efforts to therapeutically target this protein as a means of suppressing treatment-resistant disease.
Nested biofabrication: Matryoshka-inspired Intra-embedded Bioprinting
Authors: Alioglu Mecit Altan , Yilmaz Yasar Ozer , Singh Yogendra Pratap , Nagamine Momoka , Celik Nazmiye , Kim Myoung Hwan , Pal Vaibhav , Gupta Deepak , Ozbolat Ibrahim T.
Published: October 2023

Engineering functional tissues and organs remains a fundamental pursuit in biofabrication. However, the accurate constitution of complex shapes and internal anatomical features of specific organs, including their intricate blood vessels and nerves, remains a significant challenge. Inspired by the Matryoshka doll, we here introduce a new method called ‘Intra-Embedded Bioprinting (IEB),’ building upon existing embedded bioprinting methods. We used a xanthan gum-based material, which served a dual role as both a bioprintable ink and a support bath, due to its unique shear-thinning and self-healing properties. We demonstrated IEB’s capabilities in organ modelling, creating a miniaturized replica of a pancreas using a photocrosslinkable silicone composite. Further, a head phantom and a Matryoshka doll were 3D printed, exemplifying IEB’s capability to manufacture intricate, nested structures. Towards the use case of IEB and employing innovative coupling strategy between extrusion-based and aspiration-assisted bioprinting, we developed a breast tumor model that included a central channel mimicking a blood vessel, with tumor spheroids bioprinted in proximity. Validation using a clinically-available chemotherapeutic drug illustrated its efficacy in reducing the tumor volume via perfusion over time. This method opens a new way of bioprinting enabling the creation of complex-shaped organs with internal anatomical features.
Hydrophobic Clusters Direct Folding of a Synthetic Chimeric Protein
Authors: Jalan Abhishek A. , Hassine Lukas , Romero-Romero Sergio , Hübner Julian , Schweimer Kristian , Höcker Birte
Published: October 2023

Extant proteins frequently share sub-domain sized fragments, suggesting that among other mechanisms, proteins evolved new structure and functions via recombination of existing fragments. While the role of protein fragments as evolutionary units is well-established, their biophysical features necessary for generating a well-folded and stable protein are not clearly understood. In order to probe how fragments determine foldability and stability of recombined proteins, we investigated the stability, folding and dynamics of a synthetic chimera created by fusion of fragments of the chemotactic response regulator protein CheY that belongs to the flavodoxin-like fold and imidazole glycerol phosphate synthase from histidine biosynthesis (HisF) which harbors the TIM-barrel fold. The chimera unfolds via an equilibrium intermediate. Mutation of a glycine residue present at the interface of the CheY and HisF fragments to a valine abrogates the equilibrium intermediate while mutation to isoleucine dramatically increases the native state kinetic stability without any significant change in the folding rate. Parts of the fragment interface in the chimera are found to be conformationally dynamic while hydrophobic mutations globally increase its conformational rigidity. We hypothesize that the hydrophobic mutation improves sidechain packing in a large cluster of isoleucine, leucine and valine (ILV) residues that spans the fragment interface. We also extrapolate that inheritance of large ILV clusters from parent proteins could be a key determinant of successful fragment recombination.