bluuebunny/crossref_metadata_2025 huggingface dataset:
A rare case with fetal autoimmune heart block and KNCH2 variant–induced long QT syndrome: a controversial opinion on prenatal management strategy
Authors: Wei Li , Wu Jiahao , Xie Peihuan , Liu Xiaoliang , Hua Yimin , Zhou Kaiyu , Wang Chuan , Li Yifei
Published: March 2023

Background

Among all fetal heart block patients, > 50% cases are associated with maternal autoimmune diseases, and such patients should receive treatment. However, nearly half of fetal heart block cases involve a mother with negative results following autoimmune antibody screening. A few studies have reported long QT syndrome (LQTS) can also present as a severe fetal bradycardia, which does not respond to fetal treatment. Herein, we reported a rare case of an infant who presented with high-degree autoimmune-mediated fetal atrioventricular block (AVB) with LQTS induced by a novel KCNH2 variant. This case led us to review our prenatal therapeutic strategy.

Case presentation

A 1-year-old boy presented to our heart center having experienced syncope 5 times in the past year. He had previously presented with fetal bradycardia during the fetal stage from 27 + 3 gestational weeks. The fetal echocardiography demonstrated AVB (2:1 transmission). As the maternal autoimmune antibody results were positive, his mother had received dexamethasone treatment during pregnancy; subsequently, the fetal AVB had changed from 2:1 to 4:3 transmission with elevated ventricular beating rates. However, this patient was identified to have complete AVB after birth. The initial electrocardiogram and Holter measurements at hospital administration showed complete AVB, pleomorphic ventricular tachycardia, a prolonged QT interval (QT = 602 ms, corrected QT = 538 ms), and wide and deep inverted T-waves. Meanwhile, torsades de pointes could be observed in several transit ventricular tachycardias based on Holter monitoring review. Genetic testing revealed KCNH2 c.2483G > A variant–induced LQTS. An implantable cardioverter defibrillator device and permanent pacemaker were both considered as therapeutic alternations; his parents ultimately accepted the implantation of a permanent pacemaker.

Conclusions

For fetuses with autoimmune-mediated AVB, intrauterine treatment should still be pursued immediately. However, once the treatment outcomes are deemed unacceptable or unexpected, other genetic variant–related channelopathies should be highly suspected. If the fetus lacks a positive family history, fetal genetic testing should be recommended to improve the prognosis of such patients by introducing integrative therapeutic strategies between the prenatal and postnatal phases.
Integrating health promotion with and for older people - eHealth (IHOPe) – evaluating remote integrated person-centred care
Authors: Ebrahimi Zahra , Barenfeld Emmelie , Gyllensten Hanna , Olaya-Contreras Patricia , Fors Andreas , Fredholm Eva , Fuller Joanne M. , Godarzi Mahboubeh , Krantz Birgitta , Swedberg Karl , Ekman Inger
Published: March 2023

Background

Healthcare and welfare systems worldwide are unprepared to accommodate the growing population of older people. Simultaneously, the cost of reactive care for older people is increasing. However, healthcare systems in many countries are reforming towards integrated and person-centred care with a focus on health promotion and proactive actions.The Integrating Health Promotion with and for Older People – eHealth (IHOPe)project aims to describe and evaluate a person-centred e-support intervention that promotes a sustainable partnership between community-dwelling frail older people and health and social care professionals.

Methods

The IHOPe project is designed as a randomised controlled trial comparing a control group receiving standard care with an intervention group receiving standard care and add-on person-centred care through telephone support and a digital platform. The primary outcome measure is a composite score of changes in general self-efficacy and the need for unscheduled hospital care. The project is conducted in Gothenburg, Sweden. At least 220 participants aged ≥ 75 years will be included after being screened using a frailty instrument. The study design, intervention components, digital platform, and questionnaires were developed in close collaboration with an advisory group of inter-professional researchers, stakeholders, clinicians, and older representatives. Data will mainly be collected through questionnaires at baseline and 3, 6, and 12 months after inclusion in the study. Recruitment is ongoing and should be completed during 2023. Data will be analysed using quantitative and qualitative methods. The evaluation will include effectiveness, process, and health economics. The study was approved by the Regional Ethical Review Board in Gothenburg, Sweden (Dnr 2019–05364, Dnr 2020–03550, Dnr 2021–03255).

Discussion

The findings will expand our knowledge of remotely integrated person-centred care for frail older people. Thereby, the IHOPe project is expected to fill highlighted knowledge gaps on intervention evaluations including the triad of person-centred, digital, and integrated care elements, as well as economic evaluations of remote health services for frail older people. The study is ongoing, and the results are not completed but if they turn out to be positive, implementation is not limited to time or location.

Trial registration

ClinicalTrial.gov: NCT04416815. Registered 07/06/2021.
An unusual presentation of a rare disease: acute upper limb ischemia as the presenting symptom of Whipple’s Endocarditis, a case report
Authors: Chen York , Mahatanan Rattanaporn , Martin Isabella W. , de Gijsel David
Published: March 2023

Background

Whipple's disease is known to cause multiple varied systemic symptoms, and is a well-documented cause of culture-negative endocarditis. Endocarditis secondary to Whipple disease, however, has rarely been known to present primarily as a cause of acute limb ischemia. We describe such a case here.

Case presentation

A previously healthy 40 year old man presented to the emergency department with acute-onset right arm paresthesias. On exam, he was found to be tachycardic with a VI/VI systolic ejection murmur. He was diagnosed with critical limb ischemia and severe aortic regurgitation, and echocardiography showed a large mass on his bicuspid aortic valve. Thrombectomy was performed urgently, with aortic valve repair the following day. As blood cultures and valvular tissue culture remained unrevealing, the patient remained on empiric vancomycin and ceftriaxone for culture-negative endocarditis. 16 s rRNA nucleic acid amplification testing (NAAT) of his formalin-fixed, paraffin-embedded valvular tissue detected T. whipplei, after which the patient was transitioned to ceftriaxone and trimethoprim-sulfamethoxazole for a year of therapy. He continues to do clinically well.

Conclusions

We report an unusual presentation of Whipple endocarditis as an acute upper limb ischemia, absent other classic symptoms of Whipple's disease, and with diagnosis made by 16 s rRNA NAAT of valvular tissue in the setting of culture-negative endocarditis.
Polypharmacy and health related quality of life among older adults on antiretroviral therapy in a tertiary hospital in Tanzania: a hospital-based cross-sectional study
Authors: Massawe Antimon Tibursi , Shayo Grace Ambrose , Mugusi Sabina Ferdinand
Published: March 2023

Background

Human immunodeficiency virus (HIV) chronicity in the midst of old age multiplies the risk for chronic non communicable diseases. The old are predisposed to drug-drug interactions, overlapping toxicities and impairment of the quality of life (QoL) due to age-related physiological changes. We investigated polypharmacy, QoL and associated factors among older HIV-infected adults at Muhimbili National hospitals in Dar es Salaam Tanzania.

Methods

A hospital-based cross sectional study enrolled adults aged 50 years or older who were on antiretroviral therapy (ART) for ≥ 6 months. Participants’ Information including the number and type of medications used in the previous one week were recorded. Polypharmacy was defined as concurrent use of five or more non-HIV medications. A World Health Organization QoL questionnaire for people living with HIV on ART (WHOQoL HIV BREF) was used to assess QoL. A score of ≤ 50 meant poor QoLwhile > 50 meant good QoL. Polypharmacy and QoL are presented as proportions and compared using Chi-square test. Association between various factors and polypharmacy or QoL was assessed using modified Poisson regression. A p-value of < 0.05 was considered significant.

Results

A total of 285 patients were enrolled. The mean (SD) age was 57(± 6.88) years. Females were the majority (62.5%), and 42.5% were married. Polypharmacy was seen in 52 (18.2%) of participants. Presence of co-morbidities was independently associated with polypharmacy (p < 0.001). The mean(SD) score QoL for the study participants was 67.37 ± 11.Poor QoL was seen in 40 (14%) participants.All domains’ mean score were above 50, however social domain had a relatively lowmean scoreof 68 (± 10.10). Having no formal or primary education was independently associated with poor QoL (p = 0.021).

Conclusion

The prevalence of polypharmacy was modestly high and was linked to the presence of co-morbidities. No formal and/or primary education was associated with poor QoL, where by social domain of QoL was the most affected.
A serum protein signature at the time of Uveal Melanoma diagnosis predicts long-term patient survival
Authors: Herrspiegel Christina , Plastino Flavia , Lardner Emma , Seregard Stefan , Williams Pete A. , André Helder , Stålhammar Gustav
Published: March 2023

Purpose

To develop a prognostic test based on a single blood sample obtained at the time of uveal melanoma diagnosis.

Methods

83 patients diagnosed with posterior uveal melanoma between 1996 and 2000 were included. Peripheral serum samples were obtained at diagnosis and kept at -80 °C until this analysis. Protein profiling of 84 cancer-related proteins was used to screen for potential biomarkers and a prognostic test that stratifies patients into metastatic risk categories was developed (serUM-Px) in a training cohort and then tested in a validation cohort.

Results

Low serum leptin levels and high osteopontin levels were found to identify patients with poor prognosis and were therefore selected for inclusion in the final test. In the validation cohort, patient sex and American Joint Committee on Cancer stages were similarly distributed between the low, intermediate, and high metastatic risk categories. With increasing metastatic risk category, patients had shorter metastasis-free- and overall survival, as well as greater cumulative incidence of uveal melanoma-related mortality in competing risk analysis (P = 0.007, 0.018 and 0.029, respectively). In multivariate Cox regression, serUM-Px was an independent predictor of metastasis with tumor size and patient sex as covariates (hazard ratio 3.2, 95% CI 1.5–6.9).

Conclusions

A prognostic test based on a single peripheral venous blood sample at the time of uveal melanoma diagnosis stratifies patients into low, intermediate, and high metastatic risk categories. Prospective validation will facilitate its clinical utility.
Mechanical removal of epithelial hyperplasia leads to successful treatment of irregular astigmatism
Authors: de Rojas Silva Mª Victoria , Álvarez de Toledo Juan , Tobío Ruibal Adrián
Published: March 2023

Background

Corneal epithelium remodeling in response to changes in the anterior corneal surface (keratoconus, corneal refractive surgery) is well-documented in the literature. However, several conditions may induce a different behavior of the epithelium, in which focal areas of epithelial thickening induce irregular astigmatism. This case report presents a highly unusual case of irregular astigmatism induced by an epithelial hyperplasia of unknown etiology, which was treated by the mechanical removal of only the epithelium.

Case presentation

A 29-year-old woman underwent implantable collamer lens implantation to correct myopia. The patient provided written informed consent. The procedure was uneventful in both eyes. Twenty months later, she complained of decreased visual acuity in the left eye (uncorrected distance visual acuity (UCDVA) was 20/30; corrected distance visual acuity was 20/20 with + 1.00 -2.25 × 170). Corneal topography revealed a nasal steepening in the left eye. Although the corneal thickness map was normal, epithelial thickness mapping revealed a localized nasal area of epithelial hyperplasia in the left eye that matched the area of steepest curvature. Slit lamp examination showed a total clear cornea with no signs of abnormality. The patient´s medical history was unremarkable and a case of epithelial hyperplasia of unknown etiology, without active inflammation, was considered. The decision was made to perform a mechanical removal of the corneal epithelium after application of diluted alcohol. One month after the procedure, the topography of the epithelized cornea showed a regular bow tie pattern and UCDVA improved to 20/20. No recurrence of the epithelial hyperplasia was detected after twenty-one months.

Conclusions

Focal epithelial hyperplasia may induce irregular astigmatism. Epithelial thickness mapping is a very helpful technological tool to assess cases with irregular topography. De-epithelization as an isolated procedure may be useful for the successful management of these cases. Further research is required to understand the mechanism that triggers the spontaneous development of a focal epithelial hyperplasia.
Caloric restriction as a possible pitfall for persistent acromegaly follow-up – case report
Authors: Martins Ana Filipa , Santos Mónica , Rosário Francisco
Published: March 2023

Background

Acromegaly diagnosis is established when plasma levels of IGF-1 are increased and the Oral Glucose Tolerance Test (OGTT) with 75gr of glucose can’t suppress Growth Hormone (GH) levels. These two parameters are also useful during follow-up, after surgical/radiologic therapy and/or during medical therapy.

Case presentation

A 29-year-old woman was diagnosed with acromegaly after a severe headache. Previous amenorrhea and facial and acral changes were noticed. A pituitary macroadenoma was found, biochemical evaluation was in agreement with the suspected acromegaly and a transsphenoidal adenectomy was performed. As the disease recurred, a surgical reintervention and radiosurgery (Gamma Knife, 22 Gy) were necessary. No normalization of IGF-1 was achieved during three years after radiosurgery. Surprisingly, then, and although clinical features seemed getting worse, IGF-1 levels became consistently controlled to 0.3–0.8 times the upper limit of the reference range. Questioned, the patient referred that she was following an intermittent fasting dietary plan. However, based on the dietary questionnaire, she was found to be under severe caloric restriction. First OGTT (under caloric restriction) showed absence of GH suppression and an IGF-1 value of 234 ng/dL (Reference Range 76–286 ng/mL). A second OGTT, one month after an eucaloric diet was instituted, showed an increased IGF-1 of 294 ng/dL, maintaining an unsuppressed, yet less elevated, GH.

Conclusions

GHRH/GH/IGF-1 axis controls somatic growth. Regulation is complex, and nutrition status and feeding pattern have a recognized role. Like systemic inflammation or chronic liver disease, fasting and malnutrition decrease the expression of hepatic GH receptors, with consequent reduction of IGF-1 levels, through resistance to GH. This clinical report shows that caloric restriction may represent a pitfall in acromegaly follow-up.
Dietary choline and betaine intake, cardio-metabolic risk factors and prevalence of metabolic syndrome among overweight and obese adults
Authors: Abbasi Mohammad Sadegh Pour , Tousi Ayda Zahiri , Yazdani Yalda , Vahdat Sahar , Gharebakhshi Farshad , Nikrad Negin , Manzouri Ali , Ardekani Abnoos Mokhtari , Jafarzadeh Faria
Published: March 2023

Background

Choline is an important metabolite involved in phospholipids synthesis, including serum lipids, and is the immediate precursor of betaine. There are numerous studies with inconsistent results that evaluated the association between dietary choline intakes with cardiovascular risk factors. In addition, the association between dietary betaine and choline intakes with cardio-metabolic risk factors is not well studied. In the current study, our aim was to evaluate dietary choline and betaine intakes in the usual diet of obese individuals and to assess its association with serum lipids, blood pressure and glycemic markers among obese individuals.

Methods

We recruited a total number of 359 obese people aged between 20 and 50 years in the present study. A semi-quantitative food frequency questionnaire (FFQ) was used for dietary assessment; dietary choline and betaine intakes were calculated using the United States Department of Agriculture (USDA) database. National cholesterol education program adult treatment panel (NCEP-ATP)-III criteria was used metabolic syndrome (MetS) definition. Enzymatic methods were used to assess biochemical variables. Body composition was measured with the bioelectrical impedance analysis (BIA) method.

Results

Higher body mass index (BMI), waist to hip ratio (WHR), fat-free mass (FFM) and basal metabolic rate (BMR) were observed in higher tertiles of dietary choline intake (P < 0.01). There was no significant difference in terms of biochemical parameters among different tertiles of dietary choline intake, while systolic blood pressure (SBP) and diastolic blood pressure (DBP) were reduced in higher betaine tertiles (P < 0.05). For total dietary choline and betaine intakes, there was a reduction in DBP and low density lipoprotein (LDL) concentrations (P < 0.05). Also, a non-significant reduction in serum total cholesterol (TC), triglyceride (TG) and MetS prevalence was observed in higher tertiles of dietary choline and betaine intakes. After classification of the study population according to MetS status, there was no significant difference in biochemical variables in subjects with MetS (P > 0.05), while in the non-MetS group, SBP, DBP, TG and insulin levels reduced in higher tertiles of dietary betaine and choline (P > 0.05).

Conclusion

According to our findings, higher dietary intakes of choline and betaine were associated with lower levels of blood pressure and LDL concentrations among obese individuals. Further studies are warranted to confirm the results of the current study.
The effect of vitamin D on the severity of dysmenorrhea and menstrual blood loss: a randomized clinical trial
Authors: Amzajerdi Azam , Keshavarz Maryam , Ghorbali Elham , Pezaro Sally , Sarvi Fatemeh
Published: March 2023

Background

Primary dysmenorrhea is considered as one of the women’s main problems during reproductive age. The present study aimed to investigate the effect of vitamin D on the severity of dysmenorrhea and menstrual blood loss.

Methods

This double-blind, randomized, placebo-controlled trial, was performed on 84 single female college students between 18 and 25 years old who living in dormitories. Students with primary dysmenorrhea and vitamin D deficiency were divided into experimental (n = 42) and control (n = 42) groups. Five days before the putative beginning of their next menstrual cycle, the experimental group received 300,000 IU vitamin D (50,000 IU, two tablets every 8 h), and the control group received a placebo (oral paraffin). The effects of the supplement on the severity of dysmenorrhea and menstrual blood loss were evaluated one cycle before and during two successive cycles. Using the visual analog scale (VAS), verbal multidimensional scoring system (VMS), and pictorial blood assessment chart (PBLAC) questionnaires. Fisher’s exact, Chi-square, independent sample t-test and repeated measurements were used.

Results

In total, 78 of the 84 students completed the study (39 students per group). The intervention resulted in a significant reduction in the mean scores of both the VAS and VMS in the experimental group, in the first and second menstrual cycles (p < 0.001, p < 0.001, respectively), but not in the means score of PBLAC. Mefenamic acid consumption at the first and second menstruation period, in the experimental group was lower than the control group (p = 0.009, p < 0.001, respectively).

Conclusions

The results indicate that vitamin D supplementation could decrease the severity of primary dysmenorrhea and the need to consume pain-relief medications. Contrariwise vitamin D supplementation had no significant effect on menstrual blood loss.

Trial registration

This trial was registered in the Iranian Registry of Clinical Trials with code IRCT201305212324N on 18/1/2014. URL of registry: https://en.irct.ir/trial/1964.
A qualitative assessment of medical students’ readiness for virtual clerkships at a Qatari university during the COVID-19 pandemic
Authors: Bawadi Hiba , Al-Moslih Ayad , Shami Rula , Du Xiangyun , El-Awaisi Alla , Rahim Hanan Abdul , Al-Jayyousi Ghadir Fakhri
Published: March 2023

Background

This study aims to qualitatively examine the readiness of medical students to change to virtual clerkship (VC) during the pandemic, from both the faculty and students’ perspectives.

Methods

A qualitative study was conducted based on the framework of readiness to change. Focus group discussions with students, and semi-structured interviews with clinical faculty members were done using appropriate online platforms. Transcripts were then analyzed using inductive-deductive approach.

Results

Twelve themes emerged which are (1) Perceptions about the university’s decision and its communication to students, (2) A Perceived lack of clinical experience, (3) Students’ role as members of the medical team facing the pandemic, (4) Student safety, (5) Quality and design of VC and the skills it offered, (6) Belief in own ability to succeed in the VC, (7) Confidence that VC would reach its goals, (8) New enhanced learning approaches, (9) Preparing students for new types of practice in the future (10) Acquired skills, 11) Academic support and communication with faculty and college, and 12) Psychological support. Medical students showed limited readiness to undertake a virtual clerkship and not play their role as healthcare professionals during the pandemic. They perceived a huge gap in gaining clinical skills virtually and asked for a quick return to training sites.

Conclusion

Medical students were not ready for virtual clerkships. There will be a need to integrate novel learning modalities such as patient simulations and case-based learning in order to meet future demands of the medical profession and enhance the efficiency of virtual clerkships.
Parents’ recalled experiences of the child centred health dialogue in children with overweight: a qualitative study
Authors: Åsberg Malin , Derwig Mariette , Castor Charlotte
Published: March 2023

Background

Because overweight and obesity are still increasing and prevention of childhood obesity is more likely to be effective when initiated in preschool children, the Child Health Service in the south of Sweden developed a structured child-centred health dialogue model targeting all 4-year-old children and their families. The aim of this study was to describe parents’ recalled experiences of this health dialogue in children with overweight.

Methods

A qualitative inductive approach with purposeful sampling was used. Thirteen individual interviews with parents (including 11 mothers and 3 fathers) were conducted and analysed with qualitative content analysis.

Results

The analysis resulted in two categories: ‘A valuable visit with a subtle individual impact’ that described parents’ recalled experiences of the health dialogue and ‘There is a complex interaction between weight and lifestyle’ that reflected the parents’ perceptions of the relationship between their children’s weight and lifestyle.

Conclusions

Parents recalled the child-centred health dialogue as important and described discussing a healthy lifestyle as one of the obligations of the Child Health Service. Parents wanted confirmation that their family lifestyle was healthy; however, they did not want to discuss the relationship between their family lifestyle and their children’s weight. Parents expressed that when their child followed the child’s growth curve, then this indicated healthy growth. This study supports using the child-centred health dialogue as a model to provide structure for discussing a healthy lifestyle and growth but highlights the difficulties of discussing body mass index and overweight, especially in the presence of children.
Geographic accessibility and hospital competition for emergency blood transfusion services in Bungoma, Western Kenya
Authors: Mumo Eda , Agutu Nathan O. , Moturi Angela K. , Cherono Anitah , Muchiri Samuel K. , Snow Robert W. , Alegana Victor A.
Published: March 2023

Background

Estimating accessibility gaps to essential health interventions helps to allocate and prioritize health resources. Access to blood transfusion represents an important emergency health requirement. Here, we develop geo-spatial models of accessibility and competition to blood transfusion services in Bungoma County, Western Kenya.

Methods

Hospitals providing blood transfusion services in Bungoma were identified from an up-dated geo-coded facility database. AccessMod was used to define care-seeker’s travel times to the nearest blood transfusion service. A spatial accessibility index for each enumeration area (EA) was defined using modelled travel time, population demand, and supply available at the hospital, assuming a uniform risk of emergency occurrence in the county. To identify populations marginalized from transfusion services, the number of people outside 1-h travel time and those residing in EAs with low accessibility indexes were computed at the sub-county level. Competition between the transfusing hospitals was estimated using a spatial competition index which provided a measure of the level of attractiveness of each hospital. To understand whether highly competitive facilities had better capacity for blood transfusion services, a correlation test between the computed competition metric and the blood units received and transfused at the hospital was done.

Results

15 hospitals in Bungoma county provide transfusion services, however these are unevenly distributed across the sub-counties. Average travel time to a blood transfusion centre in the county was 33 min and 5% of the population resided outside 1-h travel time. Based on the accessibility index, 38% of the EAs were classified to have low accessibility, representing 34% of the population, with one sub-county having the highest marginalized population. The computed competition index showed that hospitals in the urban areas had a spatial competitive advantage over those in rural areas.

Conclusion

The modelled spatial accessibility has provided an improved understanding of health care gaps essential for health planning. Hospital competition has been illustrated to have some degree of influence in provision of health services hence should be considered as a significant external factor impacting the delivery, and re-design of available services.
Multifunctional porous poly (L-lactic acid) nanofiber membranes with enhanced anti-inflammation, angiogenesis and antibacterial properties for diabetic wound healing
Authors: Yu Hao , Li Yijia , Pan Yining , Wang Hongning , Wang Wei , Ren Xiaobin , Yuan Hang , Lv Ziru , Zuo Yijia , Liu Zhirong , Lin Wei , Yao Qingqing
Published: March 2023

With increased diabetes incidence, diabetic wound healing is one of the most common diabetes complications and is characterized by easy infection, chronic inflammation, and reduced vascularization. To address these issues, biomaterials with multifunctional antibacterial, immunomodulatory, and angiogenic properties must be developed to improve overall diabetic wound healing for patients. In our study, we prepared porous poly (L-lactic acid) (PLA) nanofiber membranes using electrospinning and solvent evaporation methods. Then, sulfated chitosan (SCS) combined with polydopamine-gentamicin (PDA-GS) was stepwise modified onto porous PLA nanofiber membrane surfaces. Controlled GS release was facilitated via dopamine self-polymerization to prevent early stage infection. PDA was also applied to PLA nanofiber membranes to suppress inflammation. In vitro cell tests results showed that PLA/SCS/PDA-GS nanofiber membranes immuomodulated macrophage toward the M2 phenotype and increased endogenous vascular endothelial growth factor secretion to induce vascularization. Moreover, SCS-contained PLA nanofiber membranes also showed good potential in enhancing macrophage trans-differentiation to fibroblasts, thereby improving wound healing processes. Furthermore, our in vitro antibacterial studies against Staphylococcus aureus indicated the effective antibacterial properties of the PLA/SCS/PDA-GS nanofiber membranes. In summary, our novel porous PLA/SCS/PDA-GS nanofiber membranes possessing enhanced antibacterial, anti-inflammatory, and angiogenic properties demonstrate promising potential in diabetic wound healing processes.
Acute subdural haematoma exacerbates cerebral blood flow disorder and promotes the development of intraoperative brain bulge in patients with severe traumatic brain injury
Authors: Zhang Shangming , Chen Qizuan , Xian Liang , Chen Yehuang , Wei Liangfeng , Wang Shousen
Published: March 2023

Background

Decompressive craniectomy (DC) is a routine procedure used for the treatment of severe traumatic brain injury (TBI) with concomitant acute subdural haematoma (SDH). However, certain patients are prone to developing malignant brain bulge during DC, which prolongs the operative time and worsens patient outcomes. Previous studies have shown that malignant intraoperative brain bulge (IOBB) may be associated with excessive arterial hyperaemia caused by cerebrovascular system disorders. Through a clinical retrospective analysis and prospective observations, we found that the cerebral blood flow of patients who possessed risk factors manifested high resistance and low flow velocity, which severely affected brain tissue perfusion and resulted in the occurrence of malignant IOBB. In the current literature, rat models of severe brain injury-associated brain bulge have rarely been reported.

Methods

To gain an in-depth understanding of cerebrovascular changes and the cascade of responses related to brain bulge, we introduced acute SDH into the Marmarou model for the preparation of a rat model of high intracranial pressure (ICP) to simulate the pathological conditions experienced by patients with severe brain injury.

Results

With the introduction of a 400-µL haematoma, significant dynamic changes occurred in ICP, mean arterial pressure, and relative blood perfusion rate of the cerebral cortical vessels. ICP increased to 56.9 ± 2.3 mmHg, mean arterial pressure showed reactive decrease, and the blood flow of cerebral cortical arteries and veins on the non-SDH-affected side decreased to < 10%. These changes could not fully recover even after DC. This resulted in generalised damage to the neurovascular unit and a lag effect to the venous blood reflux, which triggered malignant IOBB formation during DC.

Conclusion

An excessive increase in ICP causes cerebrovascular dysfunction and brings about a cascade of damage to brain tissue, which forms the basis for the development of diffuse brain swelling. The subsequent heterogeneous responses of the cerebral arteries and veins during craniotomy may be the main cause of primary IOBB. Clinicians should pay particular attention to the redistribution of CBF to various vessels when performing DC in patients with severe TBI.
How are adolescents engaged in obesity and chronic disease prevention policy and guideline development? A scoping review
Authors: Mandoh Mariam , Redfern Julie , Mihrshahi Seema , Cheng Hoi Lun , Phongsavan Philayrath , Partridge Stephanie R.
Published: March 2023

Background

Adolescent consumer engagement is widely accepted, with global calls to meaningfully involve adolescents for effective and tailored policy and guideline development. However, it is still unclear if and how adolescents are engaged. The aim of this review was to determine if and how adolescents meaningfully participate in policy and guideline development for obesity and chronic disease prevention.

Methods

A scoping review was conducted guided by the Arksey and O’Malley six stage framework. Official government websites for Australia, Canada, United Kingdom, and United States including intergovernmental organizations (World Health Organisation and United Nations) were examined. Universal databases Tripdatabase and Google advanced search were also searched. Current and published international and national obesity or chronic disease prevention policies, guidelines, strategies, or frameworks that engaged adolescents aged 10–24 years in meaningful decision-making during the development process were included. The Lansdown-UNICEF conceptual framework was used to define mode of participation.

Results

Nine policies and guidelines (n = 5 national, n = 4 international) engaged adolescents in a meaningful capacity, all focused on improving ‘health and well-being’. Demographic characteristics were poorly reported, still most ensured representation from disadvantaged groups. Adolescents were primarily engaged in consultative modes (n = 6), via focus groups and consultation exercises. Predominantly in formative phases e.g., scoping the topic or identifying needs (n = 8) and to a lesser extent in the final stage of policy and guideline development e.g., implementation or dissemination (n = 4). No policy or guideline engaged adolescents in all stages of the policy and guideline development process.

Conclusion

Overall, adolescent engagement in obesity and chronic disease prevention policy and guideline development is consultative and rarely extends throughout the entire development and implementation process.
Photon-counting CT of elbow joint fractures: image quality in a simulated post-trauma setting with off-center positioning
Authors: Sonnow Lena , Salimova Nigar , Behrendt Lea , Wacker Frank K. , Örgel Marcus , Plagge Jochen , Weidemann Friederike
Published: March 2023

Background

Photon-counting detector computed tomography (PCD-CT) has the potential to provide superior image quality compared to energy-integrating detector computed tomography (EID-CT). We compared the two systems for elbow imaging in off-center arm positioning, 90° flexion, and cast fixation in a simulated post-trauma setting.

Methods

The institutional review board approved the study protocol. In a cadaver study, an olecranon fracture was artificially created in ten whole arm specimens. Two different scanning positions were evaluated: (a) arm overhead; and (b) arm on top of the abdomen of a whole-body phantom. The ultra-high resolution mode with three dose protocols and two reconstruction kernels was applied. Two blinded radiologists independently evaluated fracture and trabecular bone delineation. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and cortical sharpness measurements were performed. Cohen κ correlations, Mann-Whitney U and Wilcoxon signed rank tests were used. A p value lower than 0.05 was considered statistically significant.

Results

Dose-equivalent PCD-CT scans were rated better for fracture and trabecular bone evaluation (p < 0.001). SNR, CNR, and cortical sharpness were higher for all diagnostic (Br76) PCD-CT images (p < 0.001). The arm position had less effect on image quality in the PCD-CT compared to the EID-CT. The use of a sharp bone kernel (Br89) improved image quality ratings for PCD-CT. In the low-dose scan mode, PCD-CT resulted in more diagnostic scans (75%) compared to EID-CT (19%).

Conclusions

PCD-CT provided superior objective and subjective image quality for fracture and trabecular bone structures delineation of the elbow compared to EID-CT in a typical post-trauma setting.

Key points

• Photon-counting detector computed tomography (PCD-CT) preserved high image quality in elbow imaging with off-center positions.

• PCD-CT was advantageous for bone evaluation in trauma elbows.

• PCD-CT ultra-high-resolution mode and very sharp reconstruction kernels facilitated higher image quality.
Effectiveness and safety of intravenous golimumab with and without concomitant methotrexate in patients with rheumatoid arthritis in the prospective, noninterventional AWARE study
Authors: Broadwell Aaron , Schechtman Joy , Conaway Douglas , Kivitz Alan , Shiff Natalie J. , Black Shawn , Xu Stephen , Langholff Wayne , Schwartzman Sergio , Curtis Jeffrey R.
Published: March 2023

Background

Biologic therapies are often prescribed for patients with rheumatoid arthritis (RA) who have inadequate responses to or are intolerant of methotrexate (MTX) and patients with poor prognostic indicators. This post hoc analysis evaluated effectiveness and safety of intravenous golimumab + MTX vs golimumab without MTX in RA patients.

Methods

AWARE, a real-world, prospective and pragmatic, Phase 4 study, compared effectiveness and safety of golimumab and infliximab in biologic-naïve and biologic-experienced patients. All treatment decisions were at the discretion of the treating rheumatologist. Effectiveness was evaluated by mean change in CDAI scores at Months 6 and 12. Safety was monitored through approximately 1 year.

Results

Among 685 golimumab-treated patients, 420 (61%) received concomitant MTX during the study and 265 (39%) did not receive MTX after enrollment; 63% and 72%, respectively, discontinued the study. Relative to golimumab without MTX, golimumab + MTX patients had shorter mean disease duration (8.7 vs 10.0 years) and a lower proportion received prior biologics (60% vs 72%); mean ± standard deviation (SD) baseline CDAI scores were similar (30.8 ± 15.1 and 32.6 ± 15.4). Mean ± SD changes from baseline in CDAI scores at Months 6 and 12, respectively, were similar with golimumab + MTX (− 10.2 ± 14.2 and − 10.8 ± 13.8) and golimumab without MTX (− 9.6 ± 12.9 and − 9.9 ± 13.1). The incidence of adverse events/100 patient-years (PY) (95% confidence interval [CI]) was 155.6 (145.6, 166.1) for golimumab + MTX and 191.2 (176.2, 207.1) for golimumab without MTX; infections were the most common type. The incidence of infusion reactions/100PY (95% CI) was 2.1 (1.1, 3.6) for golimumab + MTX versus 5.1 (2.9, 8.3) for golimumab without MTX; none were considered serious. For golimumab + MTX versus golimumab without MTX, rates/100PY (95% CI) of serious infections, opportunistic infections, and malignancies were 2.6 (1.5, 4.3) versus 7.0 (4.4, 10.6), 0.9 (0.3, 2.0) versus 2.6 (1.1, 5.0), and 3.0 (1.7, 4.7) versus 1.0 (0.2, 2.8), respectively.

Conclusions

Mean change in CDAI score in the  golimumab without MTX group was generally similar to that of the golimumab + MTX group through 1 year, regardless of prior biologic therapy. Adverse events were consistent with the known IV golimumab safety profile. These results provide real world evidential data that may assist healthcare providers and patients with RA in making informed treatment decisions.

Trial registration: clinicaltrials.gov NCT02728934 05/04/2016.
In vitro synergistic effect of hesperidin and doxorubicin downregulates epithelial-mesenchymal transition in highly metastatic breast cancer cells
Authors: Amalina Nur Dina , Salsabila Irfani Aura , Zulfin Ummi Maryam , Jenie Riris Istighfari , Meiyanto Edy
Published: March 2023

Background

We previously reported that in highly metastatic breast cancer cells, doxorubicin (DOX) at non-toxic concentrations promoted cell migration and invasion. Hesperidin (30, 5, 9-dihydroxy-40-methoxy-7-orutinosyl flavanone) is a flavonoid glycoside isolated from citrus/lemon plant that possesses a cytotoxic effect in several cancer cells. In this study, we investigate whether DOX efficacy is enhanced by hesperidin (Hsd) and the molecular pathway involved in highly metastatic breast cancer, 4T1.

Methods

Combined cytotoxicity of Hsd and DOX was evaluated with MTT assay and was analyzed using Chou-Talalay’s method. To better understand the underlying mechanism, several factors, including apoptosis and cell cycle arrest were analyzed by flow cytometry. In addition, antimigration activity was evaluated by scratch wound healing assay, MMP-9 expression by ELISA and gelatin zymography, and Rac-1 protein level using western blot. The data on survival rate and expression level of MMP-9 and Rac-1 were obtained from Gene Expression OMNIBUS (GEO).

Results

Under MTT assay, Hsd showed a cytotoxic effect in a concentration-dependent manner with an IC50 value of 284 µM on 4T1 cells. Hsd synergistically enhanced the cytotoxic effect of DOX which seemed to correlate with an increase in apoptotic cell death, G2/M cell cycle arrest and blocked the migration of 4T1 cells. At 10 nM, doxorubicin induced lamellipodia formation, and increased the level of Rac-1 and metalloproteinase-9 (MMP-9) expression. Interestingly, combined treatment of DOX and Hsd dramatically downregulated the expression of MMP-9 and Rac-1. These results indicated that Hsd block the cell migration induced by DOX under in vitro studies.

Conclusion

These findings strongly suggest that Hsd possesses a potential synergistic effect that can be developed to enhance the anticancer efficacy of DOX and reduce the risks of chemotherapy use in highly metastatic breast cancer.
Evaluating the non-invasive tools for assessment of liver fibrosis in children with intrahepatic cholestasis prior to partial biliary diversion: tertiary-center experience
Authors: El-din Hadeer Mohamed Nasr , Adel Noha , EL-koofy Nehal , Obeida Alaa , Kaddah Sherif , EL-Tagy Gamal , Mohamed Wesam
Published: March 2023

Background

The liver biopsy is an essential element of evaluating progression of liver disease in children with Progressive Familial Intrahepatic Cholestasis (PFIC) and Allagille Syndrome (AGS). Several noninvasive techniques, including radiological imaging and blood biomarkers assay, can be used to evaluate liver stiffness.

Objectives

To identify whether liver Transient elastography (FibroScan) and AST/PLT Ratio Index (APRI) could be reliable tools to assess the degree of fibrosis prior to partial biliary diversion (PBD).

Methods

A prospective cohort in which all patients with PFIC and AGS who underwent PBD from July 2019 to July 2021 were included. Preoperative liver functions, pelvic-abdominal ultrasonography and FibroScan assessments were performed while intraoperative liver biopsy was obtained.

Results

Eight patients with chronic cholestatic liver disease who were candidates for PBD due to intractable pruritus were enrolled, including PFIC (n = 6; 75%), and AGS (n = 2; 25%). The liver FibroScan results were similar to the liver biopsy histopathological assessment in 87.5% of cases. APRI ranged from 0.1 to 3.2 (median = 1.2). In four cases (50%), APRI was consistent with histological evaluation of liver samples. The FibroScan results were in concordance with APRI results in three patients (37.5%).

Conclusion

The current cohort demonstrated that fibroScan was consistent with histopathology in 87.5% of patients, highlighting its value in determining the degree of liver fibrosis prior to surgery, whereas the APRI was only consistent with histopathology in half of cases.
University Governance and the Culture of Dissent in Eighteenth-Century Charcas
Authors: Serulnikov Sergio
Published: March 2023

The article analyzes how the University of Charcas participated in public affairs in Chuquisaca (present-day Sucre) during the late colonial era. I show that following the Jesuit expulsion in the 1760s, the claustro (academic senate) became a center of university life. This body held annual elections to appoint the rector and passed governing rules for the university that allocated academic chairs based on public tenders. The faculty forcefully defended their newly gained autonomy from ecclesiastical and royal authorities, and its representative practices were instrumental in consolidating a culture of dissent that helped destabilize the unanimity principle underlying the monarchical imaginary, a principle that deemed nonconforming opinions a societal pathology incompatible with the sovereign's will and the common good. The rise of this contentious politics helped set the conditions for Chuquisaca's general uprising after the French invasion of Spain in 1808.
Comparison Between the Supracerebellar Infratentorial and Precuneal Interhemispheric, Transtentorial Approaches to the Cerebellomesencephalic Fissure: An Anatomoradiological Study and Illustrative Cases
Authors: Alexander A. Yohan , Agosti Edoardo , Leonel Luciano C. P. C. , Lanzino Giuseppe , Peris-Celda Maria
Published: March 2023

BACKGROUND:

The dorsal brainstem and cerebellomesencephalic fissure are challenging surgical targets. To afford a preferentially craniocaudal trajectory to this region, the precuneal interhemispheric transtentorial approach (PCIT) has been proposed.

OBJECTIVE:

To didactically describe and compare exposures and anatomic indications of the supracerebellar infratentorial approach (SCIT) and PCIT to the cerebellomesencephalic fissure.

METHODS:

Nine formalin-fixed, latex-injected cadaveric head specimens were used to perform a midline SCIT and bilateral PCITs and measure the distance of each approach. Twenty-four formalin-fixed specimens were used to measure the distance from the most posterior cortical bridging vein entering the superior sagittal sinus to the calcarine sulcus and the torcula. Fifty-one magnetic resonance images were reviewed to calculate the angle of each approach. Three illustrative surgical cases were described.

RESULTS:

Mean distances from the brain or cerebellar surface to the operative target of the PCIT and SCIT were 7.1 cm (range: 5-7.7 cm) and 5.5 cm (range: 3.8-6.2 cm), respectively. The SCIT provided direct access to structures of the quadrigeminal cistern bilaterally. The PCIT provided access from the ipsilateral inferior colliculus to the ipsilateral infratrochlear zone. The PCIT's benefit was the direct access it provided to the cerebellomesencephalic fissure because of its superior to inferior trajectory.

CONCLUSION:

The PCIT is indicated for unilateral lesions of the cerebellomesencephalic fissure and dorsal brainstem that harbor a craniocaudal long axis and do not have a superior extension beyond the superior colliculi. The SCIT is beneficial for lesions that extend bilaterally, have an anteroposterior long axis, or involve the Galenic complex.
Molecular profiling of the vestibular lamina highlights a key role for Hedgehog signalling
Authors: Qiu Tengyang , Hutečková Barbora , Seppala Maisa , Cobourne Martyn T. , Chen Zhi , Hovořáková Mária , Buchtová Marcela , Tucker Abigail S.
Published: March 2023

The vestibular lamina (VL) forms the oral vestibule, creating a gap between the teeth, lips and cheeks. In a number of ciliopathies, formation of the vestibule is defective, leading to the creation of multiple frenula. In contrast to the neighbouring dental lamina, which forms the teeth, little is known about the genes that pattern the VL. Here, we establish a molecular signature for the usually non-odontogenic VL in mice and highlight several genes and signalling pathways that may play a role in its development. For one of these, the Sonic hedgehog (Shh) pathway, we show that co-receptors Gas1, Cdon and Boc are highly expressed in the VL and act to enhance the Shh signal from the forming incisor region. In Gas1 mutant mice, expression of Gli1 was disrupted and the VL epithelium failed to extend due to a loss of proliferation. This defect was exacerbated in Boc/Gas1 double mutants and could be phenocopied using cyclopamine in culture. Signals from the forming teeth, therefore, control development of the VL, coordinating the development of the dentition and the oral cavity.