bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon‐γ downregulates tight junction function, which is rescued by interleukin‐17A
Authors: Mizutani Yukiko , Takagi Nao , Nagata Haruna , Inoue Shintaro
Published: July 2021

Although atopic dermatitis (AD) has been reported to be a typical type 2 immune response disease, it is also an inflammatory skin disease that involves cytokines, such as Th1, Th17 and Th22. However, little is known about the mechanism by which the candidate cytokines, alone or in combination, are involved in AD pathology. Differences in cytokine balance, which contribute to the complexity of AD pathology, may influence the stratum corneum barrier function through tight junction (TJ) functional stability and contribute to disease severity. To confirm the regulatory mechanism of TJ protein expression in AD, we investigated the Th1 and Th17 pathways, which are the initiation factors of chronic AD pathology. We examined the effects of these cytokines on TJ protein expression in normal human epidermal keratinocytes in vitro, and also examined their function in a human skin equivalent model. We observed a time‐ and dose‐dependent inhibitory effect of IFN‐γ on claudin‐1 expression via the IFN‐γ receptor/JAK/STAT signalling pathway. IFN‐γ impaired TJ function in a human skin equivalent model. Moreover, we investigated co‐stimulation with IL‐17A, which is highly expressed in AD skin lesions and found that IL‐17A restores IFN‐γ‐induced TJ dysfunction. This restoration of TJ function was mediated by atypical protein kinase C zeta activation without recovery of TJ protein expression. These results are informative for personalized AD treatment via systemic therapies using anti‐cytokine antibodies and/or JAK inhibitors.
Effect of support groups on caregiver’s quality of life
Authors: Bernabéu‐Álvarez Claudia , Lima‐Rodríguez Joaquín‐Salvador , Lima‐Serrano Marta
Published: July 2021

The objective of this study was to evaluate the effect that participating in support groups for caregivers has on the quality of life and psychotropic drug use of family caregivers of adults with limitations in activities of daily living. A controlled quasi‐experimental longitudinal design was used with 134 caregivers (64 in the experimental group and 70 in the control group). The outcomes were health‐related quality of life (EuroQol 5D3L test) and psychotropic drug use (no/yes). The analyses were performed using SPSS and R statistical software. An interaction was observed between the condition and the level of limitations in activities of daily living of the care receiver, having an effect on the caregiver's psychotropic drug use (p = 0.003), with this use being lower among caregivers who attend support groups when their relatives present fewer limitations in activities of daily living. Moreover, the quality of life was higher in the post‐test in the experimental group (B = 8.66, p = 0.015). In conclusion, support groups could improve the caregiver's quality of life and decrease psychotropic drug use when the care receiver has low limitations in activities of daily living.
SUMO wrestling in the cellular dohyō: crosstalk between phosphorylation and SUMOylation of PKCδ regulates oxidative cell damage
Authors: Zamponi Gerald W.
Published: July 2021

The novel PKCδ isoform has been shown to mediate a pro‐apoptotic function in response to oxidative stressors. Siman Gao and colleagues performed an in‐depth biochemical and molecular analysis of factors that regulate PKCδ function. They demonstrated convincingly that PKCδ is regulated by an interplay between SUMOylation and phosphorylation. They also showed that these events are critical for hydrogen peroxide induced apoptosis, thus identifying potentially novel mechanisms that may be harnessed for cell protection.

Comment on: https://doi.org/10.1111/febs.16050
A review and evaluation of the effects of hydrodynamic variables on freshwater mussel communities
Authors: Lopez Jonathan W. , Vaughn Caryn C.
Published: July 2021

Riverine species are governed by the physical (i.e. hydrodynamic) forces generated by flowing water. Freshwater species are also disproportionately imperilled compared to terrestrial and marine species in large part due to widespread anthropogenic alteration of the natural flow regimes to which organisms are adapted. Sedentary species such as freshwater mussels (Bivalvia: Unionoida) are especially vulnerable because they are unable to move quickly in response to novel flow patterns created by impoundments and water withdrawals.

We evaluated the effects of hydrodynamic variables on mussel communities. We reviewed the literature to synthesise the relationships between three categories of hydrodynamic variables (hydrologic, simple hydraulic, and complex hydraulic) and mussel community parameters. We evaluated which variables are most useful in predicting mussel presence, abundance, and species richness, provided recommendations to help standardise their use in characterising mussel habitat and reviewed the reciprocal influence of mussels on hydraulic forces at the sediment–water interface.

Hydrologic variables such as stream size and anthropogenic flow alteration were useful in predicting basin‐ and landscape‐scale changes in mussel communities. At finer scales, complex hydraulic variables—mainly shear stress and Reynolds number—were more useful at predicting mussel community responses. Simple hydraulic variables (flow velocity, depth, discharge) had mixed success as predictors of mussel community parameters and are likely to be indirectly correlated to mussel responses because they are used to calculate more complex variables.

More emphasis should be placed on species‐ and basin‐specific responses of freshwater mussels when considering the effects of the hydrologic regime on mussels, with an eye towards sustainable water management (e.g. flow restoration, environmental flows). Simple hydraulic variables should be assessed across the range of discharge at a site, in combination with channel and substrate characteristics. This allows the calculation of complex hydraulic variables that may be more directly limiting to mussel communities.

Mussels also alter near‐bed hydraulic characteristics, resulting in feedbacks between mussel community parameters and local hydraulic variable s. Researchers should consider that mussel beds have a reciprocal influence on near‐bed flow characteristics and should continue to explore the effects of such ecological engineering for possible interspecific facilitation benefits between mussel species.
Mammal assemblage composition predicts global patterns in emerging infectious disease risk
Authors: Wang Yingying X. G. , Matson Kevin D. , Santini Luca , Visconti Piero , Hilbers Jelle P. , Huijbregts Mark A. J. , Xu Yanjie , Prins Herbert H. T. , Allen Toph , Huang Zheng Y. X. , de Boer Willem F.
Published: July 2021

As a source of emerging infectious diseases, wildlife assemblages (and related spatial patterns) must be quantitatively assessed to help identify high‐risk locations. Previous assessments have largely focussed on the distributions of individual species; however, transmission dynamics are expected to depend on assemblage composition. Moreover, disease–diversity relationships have mainly been studied in the context of species loss, but assemblage composition and disease risk (e.g. infection prevalence in wildlife assemblages) can change without extinction. Based on the predicted distributions and abundances of 4466 mammal species, we estimated global patterns of disease risk through the calculation of the community‐level basic reproductive ratio R0, an index of invasion potential, persistence, and maximum prevalence of a pathogen in a wildlife assemblage. For density‐dependent diseases, we found that, in addition to tropical areas which are commonly viewed as infectious disease hotspots, northern temperate latitudes included high‐risk areas. We also forecasted the effects of climate change and habitat loss from 2015 to 2035. Over this period, many local assemblages showed no net loss of species richness, but the assemblage composition (i.e. the mix of species and their abundances) changed considerably. Simultaneously, most areas experienced a decreased risk of density‐dependent diseases but an increased risk of frequency‐dependent diseases. We further explored the factors driving these changes in disease risk. Our results suggest that biodiversity and changes therein jointly influence disease risk. Understanding these changes and their drivers and ultimately identifying emerging infectious disease hotspots can help health officials prioritize resource distribution.
A narrative review of the importance of pharmacokinetics and drug–drug interactions of preventive therapies in migraine management
Authors: Joshi Shivang , Tepper Stewart J. , Lucas Sylvia , Rasmussen Soeren , Nelson Rob
Published: July 2021

Objective

To review the pharmacokinetics of major classes of migraine preventives and the clinical implications of drug–drug interactions (DDIs) with the use of these therapies in migraine management.

Background

Preventive treatments for migraine are recommended for a large proportion of patients with frequent migraine attacks. These patients often exhibit a number of comorbidities, which may lead to the introduction of multiple concomitant therapies. Potential DDIs must be considered when using polytherapy to avoid increased risk of adverse events (AEs) or inadequate treatment of comorbid conditions.

Methods

A literature search was performed to identify pharmacokinetic properties and potential DDIs of beta‐blockers, antiepileptic drugs, antidepressants, calcium channel blockers, gepants, and monoclonal antibody therapies targeting the calcitonin gene‐related peptide pathway with medications that may be used for comorbid conditions.

Results

Most DDIs occur through alterations in cytochrome P450 isoenzyme activity and may be complicated by genetic polymorphism for metabolic enzymes. Additionally, drug metabolism may be altered by grapefruit juice ingestion and smoking. The use of migraine preventive therapies may exacerbate symptoms of comorbid conditions or increase the risk of AEs associated with comorbid conditions as a result of DDIs.

Conclusions

DDIs are important to consider in patients with migraine who use multiple medications. The development of migraine‐specific evidence‐based preventive treatments allows for tailored clinical management that reduces the risk of DDIs and associated AEs in patients with comorbidities.
Cutaneous manifestations of lupus erythematosus: a practical clinicopathological review for pathologists
Authors: Bitar Carole , Menge Tyler D , Chan May P
Published: July 2021

Accurate diagnosis of connective tissue diseases is often challenging, and relies upon careful correlation between clinical and histopathological features, direct immunofluorescence studies and laboratory work‐up. Lupus erythematosus (LE) is a prototype of connective tissue disease with a variety of cutaneous and systemic manifestations. Microscopically, cutaneous LE is classically characterised by an interface dermatitis although other histopathological patterns also exist, depending upon the clinical presentation, location and chronicity of the skin lesions. In this article, we review the clinical, serological, histopathological and direct immunofluorescence findings in LE‐specific and LE non‐specific skin lesions, with an emphasis upon lesser‐known variants, newly described features and helpful ancillary studies. This review will guide general pathologists and dermatopathologists in accurately diagnosing and subclassifying cutaneous LE.
Molecular pathology of skin adnexal tumours
Authors: Plotzke Jaclyn M , Adams David J , Harms Paul W
Published: July 2021

Aims

Tumours of the cutaneous adnexa arise from, or differentiate towards, structures in normal skin such as hair follicles, sweat ducts/glands, sebaceous glands or a combination of these elements. This class of neoplasms includes benign tumours and highly aggressive carcinomas. Adnexal tumours often present as solitary sporadic lesions, but can herald the presence of an inherited tumour syndrome such as Muir–Torre syndrome, Cowden syndrome or CYLD cutaneous syndrome. In contrast to squamous cell carcinoma and basal cell carcinoma, molecular changes in adnexal neoplasia have been poorly characterised and there are few published reviews on the current state of knowledge.

Methods and results

We reviewed findings in peer‐reviewed literature on molecular investigations of cutaneous adnexal tumours published to June 2021.

Conclusions

Recent discoveries have revealed diverse oncogenic drivers and tumour suppressor alterations in this class of tumours, implicating pathways including Ras/MAPK, PI3K, YAP/TAZ, beta‐catenin and nuclear factor kappa B (NF‐κB). These observations have identified novel markers, such as NUT for poroma and porocarcinoma and PLAG1 for mixed tumours. Here, we provide a comprehensive overview and update of the molecular findings associated with adnexal tumours of the skin.
Interobserver reproducibility of the diagnosis of differentiated exophytic vulvar intraepithelial lesion (DEVIL) and the distinction from its mimics
Authors: Neville Grace , Chapel David B , Crum Christopher P , Song Sharon J , Yoon Ju‐Yoon , Lee Kenneth R , Kolin David L , Hirsch Michelle S , Nucci Marisa R , Parra‐Herran Carlos
Published: July 2021

Aims

Most vulvar squamous cell carcinomas are human papillomavirus (HPV)‐associated or TP53‐mutant. A third category of HPV‐independent TP53‐wild‐type lesions is uncommon and not fully understood. Differentiated exophytic vulvar intraepithelial lesion (DEVIL) has been characterised as a precursor of this latter category. The reproducibility of the diagnosis of DEVIL and its distinction from lesions with overlapping morphology has not been studied. Our aim was to establish the interobserver agreement in the diagnosis of DEVIL and its distinction from neoplastic and reactive conditions of the vulva on haematoxylin and eosin evaluation.

Methods and results

A set of 35 slides was evaluated by eight reviewers (two trainees and six practising gynaecological pathologists). The set included DEVIL, condyloma, established vulvar precursors [high‐grade squamous intraepithelial lesion (HSIL) and differentiated vulvar intraepithelial neoplasia (dVIN)] with superimposed acanthosis or verruciform growth, lichen simplex chronicus (LSC), and psoriasis. Kappa (κ) values were calculated. Overall, interobserver agreement was moderate (κ = 0.56), improving to substantial (κ = 0.7) when evaluation was performed by practising pathologists. Agreement was strong for the diagnosis of HSIL (κ = 0.88), and substantial for the diagnosis of DEVIL (κ = 0.61), condyloma (κ = 0.79), and LSC (κ = 0.72). Agreement was moderate for the diagnosis of dVIN (κ = 0.59) and psoriasis (κ = 0.53). Perfect agreement (6/6) among practising pathologists was observed in 43% of cases, and majority agreement (5/6 or 4/6) was observed in 48% of cases.

Conclusions

Reproducibility in the diagnosis of verruciform vulvar lesions, including the novel DEVIL, is acceptable overall. Reproducibility is higher for well‐known lesions such as HSIL and condyloma than for more challenging diagnoses such as DEVIL, dVIN, and psoriasis. Agreement is higher among practising gynaecological pathologists, suggesting that training and experience improve reproducibility. Our findings support the inclusion of DEVIL as a diagnostic entity in the classification of vulvar squamous lesions.
Could it be gluten? Additional skin conditions associated with celiac disease
Authors: Klemm Natasha , Gooderham Melinda J. , Papp Kim
Published: July 2021

Celiac disease is a multifactorial, inflammatory disorder initiated and sustained by the ingestion of gluten. Occurring across a broad population, the intestinal and extraintestinal manifestations of celiac disease are variable in severity and may be nonspecific in presentation. Given that environmental, genetic, and immune factors involved in the pathogenesis of celiac disease that the digestive tract and skin share many characteristics, and with a prevalence of 0.5–1% in most populations, it is reasonable to consider varying presentations of skin conditions that are linked with celiac disease. The association between celiac disease and skin conditions has been discussed earlier, but new studies have emerged suggesting cutaneous involvement in addition to dermatitis herpetiformis. We review the current literature identifying the relationship and potential mechanisms between celiac disease and various skin conditions.
Optimized piezoelectric properties and temperature stability in PSN‐PMN‐PT by adjusting the phase structure and grain size
Authors: Guo Feifei , Yang Chao , Zhou Hongqiao , Dong Shasha , Fang Pinyang , Wang Junjun , Du Juan , Long Wei , Li Xiaojuan , Yang Bin , Xi Zengzhe
Published: July 2021

For relaxor ferroelectric materials, improving the piezoelectric properties and temperature stability simultaneously is still a great challenge up to now. In this work, the structure, electric properties, and thermal stability of xPSN‐(1 − x)PMN‐0.4PT (x = 0.15, 0.29, 0.43, and 0.5) ceramics were studied systematically by experiment and phase field simulation. A high Curie temperature Tc of 255℃ and good longitudinal electricmechanical coupling factor k33 of 0.75 and piezoelectric constant d33 of 650 pC/N are achieved in x = 0.43 ceramics with monoclinic C and tetragonal phases coexistence at room temperature. At 30℃, this composition ceramics sintered at 1260℃ shows the remnant polarization Pr and coercive field Ec are about 36.8 µC/cm2 and 8.2 kV/cm respectively. Moreover, as the temperature increases to 150℃, these values remain as high as 22.6 µC/cm2 and 5.7 kV/cm. In the temperature range of 30–230℃, the variation of k33 and d33 is about 24% and 25%. These high piezoelectric performance and superior temperature stability are related to the more complex domain structures caused by phase coexistence and larger grains with more stable domain structure due to internal stress. The former is beneficial in improving the piezoelectric properties, and the latter dominates the enhanced temperature stability.
Sleep and hypoglycaemia symptom perception in adults with type‐1 diabetes mellitus: A mixed‐methods review
Authors: Matus Austin , Trout Kimberly K. , Sawyer Amy M. , Riegel Barbara
Published: July 2021

Aims

The study aims to review, synthesize and integrate primary research on the relationship between sleep and hypoglycaemia symptom perception in adults with type‐1 diabetes.

Design

This mixed‐methods review follows a convergent segregated approach to synthesis and integration of qualitative and quantitative evidence.

Data Sources

With assistance of a biomedical librarian, a search of four databases was conducted (PubMed, CINAHL, Embase and PsycINFO) in June 2020. The review included primary research measuring sleep and hypoglycaemia symptom perception in adults (age ≥ 18 years) with type‐1 diabetes in English. Studies that exclusively addressed children, type‐2 diabetes or outcomes unrelated to sleep and hypoglycaemia symptom perception were excluded.

Review Methods

Screening focused on title and abstract review (n = 624). Studies not excluded after screening (n = 35) underwent full‐text review. References of each study selected for inclusion (n = 6) were hand searched with one study added. All studies included in the review (n = 7) were critically appraised with JBI Critical Appraisal tools, and then data were extracted with systematic evaluation.

Results

Quantitative synthesis found sleep reduces the magnitude of detectable symptoms and one's capacity to detect them. Qualitative synthesis found that individuals with type‐1 diabetes perceive unpredictable severity, frequency and awareness of symptoms while asleep as an oppressive, lingering threat. Integration of findings highlights the troublesome duality of sleep's relationship with hypoglycaemia symptom perception.

Conclusions

Sleep presents a challenging time for individuals with type‐1 diabetes. Further research examining the relationship between sleep and hypoglycaemia symptom perception is recommended as the number of studies limits this review.

Impact

Symptom perception is the main physiologic defense against severe hypoglycaemia in type‐1 diabetes. This review found that sleep's relationship with hypoglycaemia symptoms has unique physiological and psychological components to address when providing comprehensive care. This review may inform future lines of inquiry that develop into interventions, improvements in practice and risk reduction for hypoglycaemia‐related complications.
Complete physical examinations in Manitoba adults with an intellectual or developmental disability: A retrospective cohort study
Authors: Ratnayake Iresha , Shooshtari Shahin , Chateau Dan , Kristjanson Mark
Published: July 2021

Background

Complete physical examinations (CPE) can identify health disparities in persons with intellectual or developmental disabilities. The objective of this study was to determine and compare rates of CPE among Manitoba adults with and without intellectual or developmental disabilities over time and to identify factors that were associated with receiving a CPE.

Method

A retrospective cohort study using linked administrative health and non‐health data from 1995 to 2015 was conducted. Poisson and logistic regression were used to calculate CPE rates and examine factors associated with CPE.

Results

The rates of CPE are decreasing over time and are higher among Manitobans with an intellectual or developmental disability. Characteristics such as being male, living rurally, low socioeconomic status, and high continuity of care led to lower odds of receiving a CPE.

Conclusions

The current state of CPE provision to adults with intellectual or developmental disabilities in Manitoba is encouraging but needs improvement.
The experiences of psychologists working with people with intellectual disabilities during the COVID‐19 crisis
Authors: Embregts Petri J. C. M. , Tournier Tess , Frielink Noud
Published: July 2021

Background

The aim of this study was to explore the experiences of psychologists working with people with intellectual disabilities during the initial stage of the COVID‐19 lockdown in the Netherlands.

Method

Five psychologists, who were affiliated with three intellectual disability services, participated in this descriptive qualitative study. Overall, they recorded 22 audio messages during the period under examination, which were analysed using thematic analysis.

Results

Three themes were identified: (a) Working from home; (b) Adapting to the new reality; and (c) Advising and coaching support staff.

Conclusions

This study provides critical insights into the experiences of psychologists working with people with intellectual disabilities during the initial stage of the COVID‐19 lockdown. These insights can help policymakers and practitioners to prepare for either a potential second wave of COVID‐19 or a future pandemic.
Complete interatrial block in a left‐atrial dependent atrioventricular node
Authors: Ramos Jiménez Javier , Marco del Castillo Álvaro , Rodríguez Muñoz Daniel , Borrego Bernabé Luis , Fontenla Adolfo , López Gil María
Published: July 2021

Introduction: A middle‐age woman underwent an electrophysiologic study due to recurrent atypical atrial flutter.

Methods and Result: Radiofrequency ablation of cavotricuspid isthmus and anterior mitral line was performed. During energy delivery on the anterior left atrial wall, interatrial dissociation and complete block of the sinus impulse to the atrioventricular (AV) node was observed. AV node activation became dependent on a subsidiary left atrial rhythm.

Conclusion: Anatomical location of intra and inter‐atrial connections must be taken into account when performing extensive ablation procedures, specially in cases with prior cardiac surgeries.
Traumatic injury and atrial fibrillation among deployed service members
Authors: Alcover Karl C. , Ambardar Shiva R. , Poltavskiy Eduard , Nasir Javed M. , Janak Jud C. , Howard Jeffrey T. , Walker Lauren E. , Haigney Mark C. , Stewart Ian J.
Published: July 2021

Introduction

Atrial fibrillation and atrial flutter (AF/AFL), the most common atrial arrhythmias, have never been examined in combat casualties. In this study, we investigated the impact of traumatic injury on AF/AFL among service members with deployment history.

Methods

Sampled from the Department of Defense (DoD) Trauma Registry (n = 10,000), each injured patient in this retrospective cohort study was matched with a non‐injured service member drawn from the Veterans Affairs/DoD Identity Repository. The primary outcome was AF/AFL diagnosis identified using ICD‐9‐CM and ICD‐10‐CM codes. Competing risk regressions based on Fine and Gray subdistribution hazards model with were utilized to assess the association between injury and AF/AFL.

Results

There were 130 reported AF/AFL cases, 90 of whom were injured and 40 were non‐injured. The estimated cumulative incidence rates of AF/AFL for injured was higher compared to non‐injured patients (hazards ratio [HR] = 2.04; 95% confidence interval [CI] = 1.44, 2.87). After adjustment demographics and tobacco use, the association did not appreciably decrease (HR = 1.90; 95% CI = 1.23, 2.93). Additional adjustment for obesity, hypertension, diabetes, and vascular disorders, the association between injury and AF/AFL was no longer statistically significant (HR = 1.51; 95% CI = 0.99, 2.52).

Conclusion

Higher AF/AFL incidence rate was observed among deployed service members with combat injury compared to servicemembers without injury. The association did not remain significant after adjustment for cardiovascular‐related covariates. These findings highlight the need for combat casualty surveillance to further understand the AF/AFL risk within the military population and to elucidate the potential underlying pathophysiologic mechanisms.
Ultralow temperature cryoablation using near‐critical nitrogen for cavotricuspid isthmus‐ablation, first‐in‐human results
Authors: Klaver Martijn N. , De Potter Tom J. R. , Iliodromitis Konstantinos , Babkin Alexander , Cabrita David , Fabbricatore Davide , Boersma Lucas V. A.
Published: July 2021

Introduction

Cryoablation has evolved as a safe alternative to radiofrequency ablation in the treatment of several supraventricular arrhythmias and has potential advantages, yet is limited by the properties of the cryogen used. We investigated a novel ultralow temperature cryoablation (ULTC) system using nitrogen near its liquid‐vapor critical point as a freezing source, achieving temperatures as low as ‐196 degrees Celsius in a long linear catheter with a continuous energy release. Initial safety, procedural and efficacy outcomes of ULTC are described in patients undergoing cavotricuspid isthmus (CTI) ablation.

Methods and Results

The Cryocure studies (NCT02355106, NCT02839304) are prospective, single‐arm, multi‐center, first‐in‐human clinical studies in 17 patients with atrial flutter (AFL) and 13 patients with atrial fibrillation (AF). A total of 30 patients, mean age 65 ± 8 years old and 67% male, were enrolled and underwent ablation of the CTI. Acute success, defined as the confirmation of stable bidirectional conduction block across the CTI, was achieved in all 30 patients. After 12 months of follow‐up, 14 out of 17 AFL patients remained free from any AFL. One (3.3%) procedure‐related but not device‐related serious adverse event was reported, involving transient inferolateral ST‐elevation associated with temporary AV conduction block.

Conclusion

In this first‐in‐human clinical study the safety and performance results demonstrate the capabilities of ultralow temperature near‐critical nitrogen as an effective energy source for CTI ablation. Ongoing, larger, studies should confirm our findings and evaluate the capabilities to create linear and focal transmural lesions in other arrhythmias.
A two‐sample Mendelian randomization analysis of heart rate variability and cerebral small vessel disease
Authors: Tian Danyang , Zhang Linjing , Zhuang Zhenhuang , Huang Tao , Fan Dongsheng
Published: July 2021

Cerebral small vessel disease (cSVD) is correlated with a high risk of stroke and cognitive impairment. Previous studies between heart rate variability (HRV) and cSVD revealed paradoxical results. The authors aimed to investigate the relationship between HRV and cSVD using Mendelian randomization analysis. Genetic instruments for HRV were obtained from previous genome‐wide association studies. They applied inverse variance‐weighted analysis, weighted median analysis, simple median analysis, and Mendelian randomization–Egger regression to evaluate the associations of HRV with white matter hyperintensity (WMH) and small vessel stroke (SVS) in the UK Biobank neuroimaging dataset and the MEGASTROKE genome‐wide association study dataset. Two genetically predicted traits of HRV (the root mean square of the successive differences of inter beat intervals [RMSSD] and the peak‐valley respiratory sinus arrhythmia or high frequency power [pvRSA/HF]) were suggestively associated with WMH (β 0.26, 95% confidence interval [CI] 0.04–0.49, p = .02; β 0.14, 95% CI 0.02–0.27, p = .03, respectively). Genetically predicted traits of HRV were not significantly associated with SVS. This study provides genetic support for a suggestive causal effect of HRV (RMSSD, pvRSA/HF) on WMH but not SVS.
Cognitive assessment using the Rapid Assessment for Developmental Disabilities, Second Edition (RADD‐2)
Authors: Hom C. L. , Walsh D. , Fernandez G. , Tournay A. , Touchette P. , Lott I. T.
Published: July 2021

Background

Individuals with developmental disabilities (DD) often have severe impairments and maladaptive behaviours that make it difficult to reliably assess their cognitive abilities. Given these challenges, the Rapid Assessment of Developmental Disabilities, Second Edition (RADD‐2), was designed to measure general cognitive ability in this population. The purpose of this study is to demonstrate the battery's psychometric properties when used with individuals with DD who have challenging behavioural and psychiatric conditions and for those who have limited verbal skills.

Method

The cognitive and adaptive behaviour skills of 193 children and adults with DD and considerable medical, behavioural and/or psychiatric problems were evaluated using the first and second editions of the RADD, Kaufmann Brief Intelligence Test – 2nd Edition, and Scales of Independent Behaviour – Revised Edition. Medication side effects and challenging behaviours were assessed using the Aberrant Behaviour Checklist.

Results

There were no floor or ceiling effects on the RADD‐2. Both the nonverbal index and total scores had strong concurrent validity with other abbreviated tests of intellectual ability and good discriminant validity from measures of adaptive behaviour and medication side effects. RADD‐2 scores also had strong criterion validity as they successfully differentiated between all levels of intellectual functioning. Age and sex did not differentially affect RADD‐2 performance, and the co‐occurrence of psychiatric conditions did not negatively affect performance. The only medical condition associated with lower RADD‐2 performance was epilepsy.

Conclusions

The RADD‐2 can quantify the differential cognitive abilities of individuals with DD, even for those with minimal communication skills, challenging behaviours or severe medication side effects that can typically complicate assessment. This brief cognitive battery can be used to measure changes due to interventions, on the one hand, and progression of neurological disease, on the other.
End‐of‐life: An urgent update in nursing terminology
Authors: Bragança Joana , Martins Lurdes , Campos de Carvalho Emília , Vieira Margarida , Caldeira Sílvia
Published: July 2021

Although nursing terminologies and classifications represent nursing knowledge across diverse clinical areas, end‐of‐life care seems under represented in many aspects of these instruments. NANDA‐ I is an international nursing diagnostic classification widely used in nursing education and research. This taxonomy is based on seven axes, including the axis of time. In this commentary we bring discussion to the need to update nursing terminology by including the term end‐of‐life in the time axis of NANDA‐I. After describing the epidemiologic aspects of end‐of‐life care and discussing the relevant nursing role, we discuss patients' and family's human responses towards the end‐of‐life time and circumstance, which are central to defining nursing diagnoses. End‐of‐life care is one priority in health care, and nursing diagnoses should represent that situation as well.

This paper focuses on a specific and international nursing diagnosis classification, NANDA‐I, which lacks an end‐of‐life component to its time axis for defining labels of nursing diagnoses. Attending to the importance of classifications in clinical reasoning, nursing diagnoses could better represent responses towards this health condition, opening new opportunities for increasing nursing roles in clinical practice, and also for new studies aiming to validate nursing diagnoses, and promoting an evidence‐based practice by including end‐of‐life in the axis time.
Factors related to complex care needs of older adults in community‐based integrated care centers in Japan: A cross‐sectional study
Authors: Yoshioka‐Maeda Kyoko , Kono Ayumi
Published: July 2021

Aim

This study aimed to identify the factors related to complex care needs of older adults in community‐based integrated care centers.

Methods

We sent 936 self‐reported questionnaires to community‐based integrated care center directors in the Kinki region of Japan. These questionnaires included questions not only about the directors' demographic data, but also regarding the sociodemographic, psychosocial, and family‐related dimensions of the older adults in the community centers. The directors divided their cases into two categories: “Complex cases” and “Straightforward cases.” We compared the intergroup differences and examined the factors related to complex care needs in older adults.

Results

A total of 232 directors responded. Complex cases were significantly associated with younger age, poor health conditions, and having a family member who needs care, as compared to straightforward cases where these associations were not present. Logistic regression showed that in older adults, factors of refusing support or social services, social isolation, and trouble with neighbors were associated with their complexities. Additionally, family members with a high likelihood of refusing social services, older adults without a key family member, and difficulties in forming their consensus regarding care were associated with older adults' complexities.

Conclusion

Older adults with complex care needs could have the risk of self‐neglect, and their families faced difficulties in supporting them as family members. Healthcare professions should carefully assess these factors and develop needs‐oriented services for them without their family support as an upstream intervention.
Male lip filler—Aesthetic enhancement is not just limited to females: A case report
Authors: Goel Anupriya , Rai Kritika
Published: July 2021

Background

Lips play an important role in facial aesthetics. Hyaluronic acid fillers have been widely used for lip augmentation in females but very few men seek this treatment due to the fear of feminization of lips. However, there are very few case reports published for correction of lips using fillers in men.

Aim

To assess the effectiveness of hyaluronic acid dermal fillers for enhancement of lips in males.

Method

A 52‐year‐old male underwent two sessions of treatment for inturned lips. In the first session, 2 ml hyaluronic acid dermal filler (Juvederm Ultra Plus—JUP) with 27G × 8 mm needle via bolus and retrograde linear thread technique was used. Assessment of lips was done after one week. Second session of treatment was done after 30 months of first treatment with 1 ml of filler.

Results

Injection of filler not only led to a significant improvement in vermillion show, but also improved the overall facial appearance. The results of this treatment were long lasting and even after 30 months from the first treatment the patients’ vermillion body still showed ten per cent improvement from the original.

Conclusion

Dermal lip filler treatment in men can be a very satisfying and rewarding procedure. Its awareness should be spread afar to increase its acceptability.
Pagetoid dyskeratosis with a palmar localization: Rapid resolution following biopsy
Authors: Falay Gür Tuğba , Savaş Erdoğan Sevil , Sade Ayşe Gökçen
Published: July 2021

Background

Pagetoid dyskeratosis (PD), which is found in more than 2% of skin biopsy specimens, is accepted as a histopathological finding reflecting the abnormal keratinization process. However, to date, only a limited number of cases have been described to have brown pigmentation on the hands, triggered by friction, and present with pagetoid dyskeratosis as the only sign on histopathology and a parallel ridge pattern on dermoscopy.

Aim

To present and discuss the typical clinical, histopathological, and dermoscopic features of pagetoid dyskeratosis, and to draw attention to the spontaneous resolution following biopsy.

Patient

We present a case of pagetoid dyskeratosis with a palmar localization, which rapidly resolved following biopsy, in a patient with no history of friction.

Results

PD is the only important histopathological finding in typical irregular pigmented lesions located in the hand. PD should also be considered in the differential diagnosis of lesions that show parallel ridge pattern on the hand. Two weeks after the biopsy, disappearance of the lesion may be due to the effect of inflammatory response revealed by biopsy.

Conclusions

Although the cause of this condition is not yet fully understood, most cases being associated with friction or rapid spontaneous resolution following biopsy, as in the current case, may indicate the reactive nature of the lesion. Further researches are required to be clarify etiology of PD.
Technological readiness and implementation of genomic‐driven precision medicine for complex diseases
Authors: Franks P. W. , Melén E. , Friedman M. , Sundström J. , Kockum I. , Klareskog L. , Almqvist C. , Bergen S. E. , Czene K. , Hägg S. , Hall P. , Johnell K. , Malarstig A. , Catrina A. , Hagström H. , Benson M. , Gustav Smith J. , Gomez M. F , Orho‐Melander M. , Jacobsson B. , Halfvarson J. , Repsilber D. , Oresic M. , Jern C. , Melin B. , Ohlsson C. , Fall T. , Rönnblom L. , Wadelius M. , Nordmark G. , Johansson Å. , Rosenquist R. , Sullivan P. F.
Published: July 2021

The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment – genomic‐driven precision medicine (GDPM) – may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single‐gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non‐genetic data.
Psychophysical evaluation of somatosensory function in oro‐facial pain: achievements and challenges
Authors: Costa Yuri M. , Bonjardim Leonardo R. , Conti Paulo César R. , Svensson Peter
Published: July 2021

Aim

This critical review describes key methodological aspects for a successful oro‐facial psychophysical evaluation of the somatosensory system and highlights the diagnostic value of somatosensory assessment and management perspectives based on somatosensory profiling.

Methods

This topical review was based on a non‐systematic search for studies about somatosensory evaluation in oro‐facial pain in PubMed and Embase.

Results

The recent progress regarding the psychophysical evaluation of somatosensory function was largely possible due to the development and application of valid, reliable and standardised psychophysical methods. Qualitative sensory testing may be useful as a screening tool to rule out relevant somatosensory abnormalities. Nevertheless, the patient should preferably be referred to a more comprehensive assessment with the quantitative sensory testing battery if confirmation of somatosensory abnormalities is necessary. Moreover, the identification of relevant somatosensory alterations in chronic pain disorders that do not fulfil the current criteria to be regarded as neuropathic has also increased the usefulness of somatosensory evaluation as a feasible method to better characterise the patients and perhaps elucidate some underpinnings of the so‐called ‘nociplastic’ pain disorders. Finally, an additional benefit of oro‐facial pain treatment based on somatosensory profiling still needs to be demonstrated and convincing evidence of somatosensory findings as predictors of treatment efficacy in chronic oro‐facial pain awaits further studies.

Conclusion

Psychophysical evaluation of somatosensory function in oro‐facial pain is still in its infancy but with a clear potential to continue to improve the assessment, diagnosis and management of oro‐facial pain patients.
The psychology of ultimate values: A computational perspective
Authors: Rigoli Francesco
Published: July 2021

Ultimate values can be defined as abstract rules or goals transcending specific contexts and defining the utmost purposes of existence. Although the literature about human values is vast, several fundamental questions about ultimate values remain open. What are the processes responsible for the formation of ultimate values? What is the impact of inbuilt affective processes and of learning, respectively? Regarding learning, what is the role of society? Empirical evidence shows dramatic variability in ultimate values pursued by different people. Why? These open questions suggest that a precise picture of ultimate values is lacking. This paper offers a computational theory of ultimate values. The key idea is that our brain represents values along a hierarchy where ultimate values are built upon experiences with inherent affective nature (basic values). Based on these representations, the proposal is that the brain infers the rules that foster basic values in a variety of contexts. These would become ultimate values and drive human behaviour independent of the ongoing context. We discuss how the theory can contribute to understanding a variety of aspects of human values, including morality, to what degree values are innate or culturally determined, and how values shape and are shaped by society.
Testing Goodwin with a stochastic differential approach—The United States (1948–2019)
Authors: McIsaac Florent
Published: July 2021

This paper follows Harvie and Grasselli and Maheshwari's research program in testing both Goodwin's predator–prey model and the extension proposed by van der Ploeg. The aim of this paper is to provide a guideline for the bloc estimation and the backtesting strategy that can be applied to such a class of continuous‐time non‐linear macroeconomic models. The goal of this paper is to propose and test stochastic differential equations for Goodwin's model and one of its extensions by an estimation technique based on simulated maximum likelihood developed by Durham and Gallant. The data considered here are that of wage share and employment rate in the United States from 1948:Q1 to 2019:Q4. Results show that two structural breaks—at the beginning of the 80s' and late 90s'—are likely to have occurred and the Goodwin‐type model endowed with Leontief production technology explains more accurately the data than the van der Ploeg's CES production function. These results are partly confirmed by a backtesting strategy, which highlights the predicting property of the van der Ploeg‐like model on a purely statistical VAR model. Both the estimation and backtesting strategies can be used to assess the empirical improvement on any extensions of the models investigated in this paper.
Activation of CRF1 receptors expressed in brainstem autonomic nuclei stimulates colonic enteric neurons and secreto‐motor function in male rats
Authors: Yuan Pu‐Qing , Wu S. Vincent , Stengel Andreas , Sato Ken , Taché Yvette
Published: July 2021

Background

Hypothalamic corticotropin‐releasing factor (CRF) receptor 1 (CRF1) plays a role in acute stress‐related stimulation of colonic motor function. Less is known on CRF1 signaling in the brainstem.

Methods

We investigate CRF1 expression in the brainstem and the colonic response to 4th ventricle (4V) injection of CRF and urocortin (Ucn) 2 (3 µg/rat) in chronically cannulated male rats.

Key results

Transcripts of CRF1 wild‐type 1a and splice variants 1c, 1e, 1f, 1o along with three novel variants 1a‐2 (desK‐110 in exon 5), 1p (‐exon 7), and 1q (exon 5 extension) were identified in the pons and medulla. The area postrema, nucleus tractus solitarius, dorsal motor nucleus of the vagus, locus coeruleus, and Barrington’s nucleus isolated by laser capture microdissection expressed 1a, 1a‐2, and 1p but not 1q. Compared to 4V vehicle, 4V CRF induced fecal pellet output (FPO) and diarrhea that were blocked by the CRF antagonist, astressin‐B. CRF2 agonist, Ucn2 had no effect on basal or CRF‐induced FPO. CRF actions were correlated with the induction of c‐Fos immunoreactivity in myenteric neurons of the proximal and distal colon (pC, dC) and submucosal neurons of dC. c‐Fos immunoreactivity occurred in 39% and 37% of myenteric cholinergic and 7% and 58% of nitrergic neurons in the pC and dC, respectively.

Conclusions & Inferences

CRF1a and its splice variants are expressed in brainstem nuclei, and activation of CRF1 signaling at the level of the brainstem stimulates colonic secretory‐motor function through activation of colonic enteric neurons.