bluuebunny/crossref_metadata_2025 huggingface dataset:
The morphology of the proximal femur in cementless short-stem total hip arthroplasty: No negative effect on offset reconstruction, leg length difference and implant positioning
Authors: Luger Matthias , Feldler Sandra , Klasan Antonio , Gotterbarm Tobias , Schopper Clemens
Published: December 2021

Background

Correct reconstruction of hip offset (HO) and leg length are important for clinical–functional outcome and patient satisfaction in total hip arthroplasty (THA). The morphology of the proximal femur can pose a risk for increased leg length difference (LLD) in cementless straight-stem THA. We therefore wanted to evaluate, if this is also applicable in THA with a cementless meta-diaphyseal short stem.

Methods

In a retrospective study, 106 patients (index surgery 2014–2019) with unilateral THA and a morphologically healthy hip as a reference (Kellgren–Lawrence ≤ 1) were included. The same cementless short stem with meta-diaphyseal fixation and cementless press-fit cup was implanted. The proximal femur was rated by Dorr’s classification, and subgroups were formed afterward. Measurements were carried out on preoperative and 3 months postoperative anterior–posterior radiographs of the pelvis. Kruskal–Wallis test, Fisher’s exact test and binary logistic regression were performed to evaluate the influence of the anatomical shape on postoperative leg length difference and offset reconstruction.

Results

The Dorr type did not show any significance influence on LLD (p = 0.532), or postoperative difference in femoral offset (p = 0.243), acetabular offset (p = 0.106) and hip offset (p = 0.698). Stem alignment (p = 0.705) and canal fill indices (CFI I: p = 0.321; CFI II: p = 0.411; CFI III: p = 0.478) were also without significant differences. Logistic regression did not show any significant increased risk for a LLD ≥ 5 mm or ≥ 10 mm as well as HO ≥ 5 mm or ≥ 10 mm.

Conclusion

Reconstruction of hip offset and postoperative leg length difference is not negatively influenced by Dorr type, canal flare index, cortical index and canal-to-calcar ratio in cementless short-stem THA. Implant positioning and canal fill are also not negatively affected by the anatomical shape of the proximal femur.

Level of evidence: Level IV.
Chinese herbal medicine for functional dyspepsia: a network meta-analysis of prokinetic-controlled randomised trials
Authors: Ho Leonard , Zhong Claire C. W. , Wong Charlene H. L. , Wu Justin C. Y. , Chan Karina K. H. , Wu Irene X. Y. , Leung Ting Hung , Chung Vincent C. H.
Published: December 2021

Background

Prokinetic is the first-line conventional treatment for functional dyspepsia (FD) in Asia despite potential adverse events. Chinese herbal medicine (CHM) may be an effective and safe substitution. This network meta-analysis (NMA) aimed to evaluate the comparative effectiveness of different CHM formulae for FD against prokinetics.

Methods

Seven international and Chinese databases were searched from their inception to July 2020 for randomised controlled trials (RCTs) on CHM versus prokinetics. Data from each RCT were first pooled using random-effect pairwise meta-analyses and illustrated as risk difference (RD) or standardised mean difference (SMD) with 95% confidence interval (CI). Random-effect NMAs were then performed to evaluate the comparative effectiveness of CHM formulae and displayed as RD with 95% CI or SMD with 95% credible interval (CrI). The GRADE partially contextualised framework was applied for NMA result interpretation.

Results

Twenty-six unique CHM formulae were identified from twenty-eight RCTs of mediocre quality. Pairwise meta-analyses indicated that CHM was superior to prokinetics in alleviating global symptoms at 4-week follow-up (pooled RD: 0.14; 95% CI: 0.10–0.19), even after trim and fill adjustment for publication bias. NMAs demonstrated that Modified Zhi Zhu Decoction may have a moderate beneficial effect on alleviating global symptoms at 4-week follow-up (RD: 0.28; 95% CI: − 0.03 to 0.75). Xiao Pi Kuan Wei Decoction may have a large beneficial effect on alleviating postprandial fullness (SMD: − 2.14; 95% CI: − 2.76 to 0.70), early satiety (SMD: − 3.90; 95% CI: − 0.68 to − 0.42), and epigastric pain (SMD: − 1.23; 95% CI: − 1.66 to − 0.29). No serious adverse events were reported.

Conclusion

Modified Zhi Zhu Decoction and Xiao Pi Kuan Wei Decoction may be considered as an alternative for patients unresponsive to prokinetics. Confirmatory head-to-head trials should be conducted to investigate their comparative effectiveness against prokinetics.
A new approach to identifying patients with elevated risk for Fabry disease using a machine learning algorithm
Authors: Jefferies John L. , Spencer Alison K. , Lau Heather A. , Nelson Matthew W. , Giuliano Joseph D. , Zabinski Joseph W. , Boussios Costas , Curhan Gary , Gliklich Richard E. , Warnock David G.
Published: December 2021

Background

Fabry disease (FD) is a rare genetic disorder characterized by glycosphingolipid accumulation and progressive damage across multiple organ systems. Due to its heterogeneous presentation, the condition is likely significantly underdiagnosed. Several approaches, including provider education efforts and newborn screening, have attempted to address underdiagnosis of FD across the age spectrum, with limited success. Artificial intelligence (AI) methods present another option for improving diagnosis. These methods isolate common health history patterns among patients using longitudinal real-world data, and can be particularly useful when patients experience nonspecific, heterogeneous symptoms over time. In this study, the performance of an AI tool in identifying patients with FD was analyzed. The tool was calibrated using de-identified health record data from a large cohort of nearly 5000 FD patients, and extracted phenotypic patterns from these records. The tool then used this FD pattern information to make individual-level estimates of FD in a testing dataset. Patterns were reviewed and confirmed with medical experts.

Results

The AI tool demonstrated strong analytic performance in identifying FD patients. In out-of-sample testing, it achieved an area under the receiver operating characteristic curve (AUROC) of 0.82. Strong performance was maintained when testing on male-only and female-only cohorts, with AUROCs of 0.83 and 0.82 respectively. The tool identified small segments of the population with greatly increased prevalence of FD: in the 1% of the population identified by the tool as at highest risk, FD was 23.9 times more prevalent than in the population overall. The AI algorithm used hundreds of phenotypic signals to make predictions and included both familiar symptoms associated with FD (e.g. renal manifestations) as well as less well-studied characteristics.

Conclusions

The AI tool analyzed in this study performed very well in identifying Fabry disease patients using structured medical history data. Performance was maintained in all-male and all-female cohorts, and the phenotypic manifestations of FD highlighted by the tool were reviewed and confirmed by clinical experts in the condition. The platform’s analytic performance, transparency, and ability to generate predictions based on existing real-world health data may allow it to contribute to reducing persistent underdiagnosis of Fabry disease.
Clinical, humanistic, and economic burden of severe haemophilia B in adults receiving factor IX prophylaxis: findings from the CHESS II real-world burden of illness study in Europe
Authors: Burke Tom , Asghar Sohaib , O’Hara Jamie , Chuang Margaret , Sawyer Eileen K. , Li Nanxin
Published: December 2021

Background

Real-world studies of the burden of severe haemophilia B in the context of recent therapeutic advances such as extended half-life (EHL) factor IX (FIX) products are limited. We analysed data from the recent CHESS II study to better understand the clinical, humanistic, and economic burden of severe haemophilia B in Europe. Data from male adults with severe haemophilia B receiving prophylaxis were analysed from the retrospective cross-sectional CHESS II study conducted in Germany, France, Italy, Spain and the United Kingdom. Inhibitors were exclusionary. Patients and physicians completed questionnaires on bleeding, joint status, quality of life, and haemophilia-related direct and indirect costs (2019–2020). All outcomes were summarised using descriptive statistics.

Results

A total of 75 CHESS II patients were eligible and included; 40 patients (53%) provided self-reported outcomes. Mean age was 36.2 years. Approximately half the patients were receiving EHL versus standard half-life (SHL) prophylaxis (44% vs 56%). Most patients reported mild or moderate chronic pain (76%) and had ≥ 2 bleeding events per year (70%), with a mean annualised bleed rate of 2.4. Mean annual total haemophilia-related direct medical cost per patient was €235,723, driven by FIX costs (€232,328 overall, n = 40; €186,528 for SHL, €290,620 for EHL). Mean annual indirect costs (€8,973) were driven by early retirement or work stoppage due to haemophilia. Mean quality of life (EQ-5D) score was 0.67.

Conclusions

These data document a substantial, persistent real-world burden of severe haemophilia B in Europe. Unmet needs persist for these patients, their caregivers, and society.
TDP-43 Pathology in Alzheimer’s Disease
Authors: Meneses Axel , Koga Shunsuke , O’Leary Justin , Dickson Dennis W. , Bu Guojun , Zhao Na
Published: December 2021

Transactive response DNA binding protein of 43 kDa (TDP-43) is an intranuclear protein encoded by the TARDBP gene that is involved in RNA splicing, trafficking, stabilization, and thus, the regulation of gene expression. Cytoplasmic inclusion bodies containing phosphorylated and truncated forms of TDP-43 are hallmarks of amyotrophic lateral sclerosis (ALS) and a subset of frontotemporal lobar degeneration (FTLD). Additionally, TDP-43 inclusions have been found in up to 57% of Alzheimer’s disease (AD) cases, most often in a limbic distribution, with or without hippocampal sclerosis. In some cases, TDP-43 deposits are also found in neurons with neurofibrillary tangles. AD patients with TDP-43 pathology have increased severity of cognitive impairment compared to those without TDP-43 pathology. Furthermore, the most common genetic risk factor for AD, apolipoprotein E4 (APOE4), is associated with increased frequency of TDP-43 pathology. These findings provide strong evidence that TDP-43 pathology is an integral part of multiple neurodegenerative conditions, including AD. Here, we review the biology and pathobiology of TDP-43 with a focus on its role in AD. We emphasize the need for studies on the mechanisms that lead to TDP-43 pathology, especially in the setting of age-related disorders such as AD.
Surgical treatment of post-traumatic luxation of rib heads with spinal cord compression in a cat
Authors: Sterna Jacek Cezary , Rogowska Laura , Degórska Beata , Sobczyński Jacek , Łumińska Monika
Published: December 2021

Background

Luxation of the rib head with intrusion into the intervertebral foramen seems to be rare in cats. Only one report has been published describing a cat with non-ambulatory paraparesis, which was managed conservatively. Here we report a case of rib head luxation that was managed surgically.

Case presentation

A 4-year-old, female domestic shorthair cat with a two-week history of non-ambulatory paraparesis was presented at our clinic. Based on history and neurological examination, a diagnosis of thoracolumbar spinal cord lesion of traumatic origin was made. Computed tomography scanning revealed mild scoliosis, a luxation of the 3rd and 4th right rib heads and penetration into the spinal canal through intervertbral foramina. Surgical management using right dorsal approach to the spine was performed. The spinal cord was decompressed by cutting and removing of proximal ribs’ fragments by rotation and pulling out from the intervertebral foramina. The cat was ambulatory and paraparetic four weeks after surgery. Two years after surgery the cat regained functional gait, but ataxia remained.

Conclusions

We report the first case of a surgical treatment of rib head luxation and intrusion into the spinal canal in a cat. The applied procedure resulted in an improvement of neurological signs.
Malaria vector control tools in emergency settings: What do experts think? Results from a DELPHI survey
Authors: Boëte Christophe , Burza Sakib , Lasry Estrella , Moriana Silvia , Robertson William
Published: December 2021

Background

The use and implementation of novel tools for malaria control such as long lasting impregnated bednets (LLINs) and Indoor Residual Spraying (IRS) over the last decade has contributed to a substantial reduction in malaria burden globally. However numerous challenges exist particularly in relation to vector control in emergency settings. This study seeks to explore expert opinion on the utility of existing tools within the emergency context setting and to better understand the attitude towards emerging and innovative tools (including Genetically Modified Mosquitoes) to augment current approaches.

Methods

80 experts in the field of malaria and vector control were invited to participate in a two-round Delphi survey. They were selected through a combination of literature (academic and policy publications) review and snowball sampling reflecting a range of relevant backgrounds including vector control experts, malaria programme managers and emergency response specialists. The survey was conducted online through a questionnaire including the possibility for free text entry, and concentrated on the following topics:

Utility and sustainability of current vector control tools, both in and outside emergency settings

Feasibility, utility and challenges of emerging vector control tools, both in and outside emergency settings

Current and unmet research priorities in malaria vector control and in malaria control in general.

Results

37 experts completed the first round and 31 completed the second round of the survey. There was a stronger consensus about the increased utility of LLIN compared to IRS in all settings, while insecticide-treated covers and blankets ranked very high only in emergency settings. When considering the combination of tools, the ones deemed most interesting always involved LLINs and IRS regardless of the setting, and the acceptability and the efficacy at reducing transmission are essential characteristics. Regarding perceptions of tools currently under development, consensus was towards improvement of existing tools rather than investing in novel approaches and the majority of respondents expressed distrust for genetic approaches.

Conclusion

Malaria vector control experts expressed more confidence for tools whose efficacy is backed up by epidemiological evidence, hence a preference for the improvement rather than the combination of existing tools. Moreover, while several novel tools are under development, the majority of innovative approaches did not receive support, particularly in emergency settings. Stakeholders involved in the development of novel tools should involve earlier and raise awareness of the potential effectiveness amongst a wider range of experts within the malaria community to increase acceptability and improve early adoption once the evidence base is established.
Shifting North American drug markets and challenges for the system of care
Authors: Krausz R. Michael , Westenberg Jean N. , Mathew Nickie , Budd George , Wong James S. H. , Tsang Vivian W. L. , Vogel Marc , King Conor , Seethapathy Vijay , Jang Kerry , Choi Fiona
Published: December 2021

Drug markets are dynamic systems which change based on demand, competition, legislation and revenue. Shifts that are not met with immediate and appropriate responses from the healthcare system can lead to public health crises with tragic levels of morbidity and mortality, as experienced Europe in the early 1990s and as is the case in North America currently. The major feature of the current drug market shift in North America is towards highly potent synthetic opioids such as fentanyl and fentanyl analogues. An additional spike in stimulant use further complicates this issue. Without understanding the ever-changing dynamics of drug markets and consequent patterns of drug use, the healthcare system will continue to be ineffective in its response, and morbidity and mortality will continue to increase. Economic perspectives are largely neglected in research and clinical contexts, but better treatment alternatives need to consider the large-scale macroeconomic conditions of drug markets as well as the behavioural economics of individual substance use. It is important for policy makers, health authorities, first responders and medical providers to be aware of the clinical implications of drug market changes in order to best serve people who use drugs. Only with significant clinical research, a comprehensive reorganization of the system of care across all sectors, and an evidence-driven governance, will we be successful in addressing the challenges brought on by the recent shifts in drug markets.
MEIS2 (15q14) gene deletions in siblings with mild developmental phenotypes and bifid uvula: documentation of mosaicism in an unaffected parent
Authors: Zhang Bin , Liu Michel , Fong Chin-To , Iqbal M. Anwar
Published: December 2021

MEIS2 (Meis homeobox 2) encodes a homeobox protein in the three amino acid loop extension (TALE) family of highly conserved homeodomain-containing transcription regulators important for development. MEIS2 deletions/mutations have been associated with cleft lip/palate, dysmorphic facial features, cardiac defects, as well as intellectual disability at a variable severity. Here we report on one familial case that two affected siblings carry the same non-mosaic ~ 423 kb genomic deletion at 15q14 encompassing the entirety of CDIN1 and the last three exons (ex. 10, 11, 12) of the MEIS2 gene, while their unaffected father is mosaic for the same deletion in about 10% lymphocytes. Both siblings presented with mild developmental delay and bifid uvula, while no congenital cardiac abnormalities were identified. The elder sister also showed syncopal episodes and mild speech delay and the father had atrial septal defects. This is the first report showing multiple family members inherit a genomic deletion resulting in a MEIS2 partial truncation from a mosaic parent. Taken all together, this study has important implications for genetic counseling regarding recurrence risk and also points to the importance of offering MEIS2 gene tests covering both point mutations and microdeletions to individuals with milder bifid uvula and developmental delay.
A pilot study of trained ICU doulas providing early psychological support to critically ill patients
Authors: Karnatovskaia Lioudmila V. , Varga Katalin , Niven Alexander S. , Schulte Phillip J. , Mujic Midhat , Gajic Ognjen , Bauer Brent A. , Clark Matthew M. , Benzo Roberto P. , Philbrick Kemuel L.
Published: December 2021

Background

Over a third of critical illness survivors suffer from mental health problems following hospitalization. Memories of delusional experiences are a major risk factor. In this project, ICU doulas delivered a unique positive suggestion intervention targeting the vulnerable time period during critical illness when these memories are formed.

Methods

Adult critically ill patients were recruited for this single-arm, prospective pilot study. These ICU patients received a positive suggestion intervention daily during their ICU stay in parallel with their medical treatment. The intervention was designed to be delivered over a minimum of two sessions. Feasibility was defined as intervention delivery on ≥ 70% of ICU days after patient enrollment. As a secondary analysis, psychometric questionnaires were compared to those of a historic control cohort of patients receiving standard care in the ICU using adjusted linear regression models.

Results

Of the 97 patients who received the intervention and were alive at the end of their ICU course, 54 were excluded from analyses mostly for having received only one session because of a short ICU length of stay of < 2 days, transitioning to comfort care or not wanting to answer the study questionnaires. Forty-three patients who completed 2 or more sessions of the positive therapeutic suggestion intervention provided by two trained ICU doulas received it for a median of 4 days (IQR 3, 5), with each session lasting for a median of 20 min (IQR 14, 25). The intervention was delivered on 71% of days, meeting our pre-determined feasibility goal. Compared to historical controls (N = 299), patients receiving the intervention had higher severity of illness and longer length of stay. When adjusted for baseline differences, patients both with and without mechanical ventilation who received the intervention scored lower on the Hospital Anxiety and Depression Scale (HADS)—Depression subscale. The intervention was also associated with reduced HADS-Anxiety subscale among ventilated patients.

Conclusions

Positive therapeutic suggestion delivered by ICU doulas is feasible in the ICU setting. A randomized trial is warranted to better delineate the role that positive suggestion and ICU doulas may play in ongoing interprofessional efforts to humanize critical care medicine.

The study was registered on clinicaltrials.gov (NCT03736954) on 03/14/2018 prior to the first patient enrollment https://clinicaltrials.gov/ct2/show/NCT03736954?cond=ICU+Doulas+Providing+Psychological+Support&draw=2&rank=1.
Promoting Independence Through quality dementia Care at Home (PITCH): a research protocol for a stepped-wedge cluster-randomised controlled trial
Authors: Savvas Steven , Goh Anita M. Y. , Batchelor Frances , Doyle Colleen , Wise Erica , Tan Esther , Panayiotou Anita , Malta Sue , Winbolt Margaret , Clarke Phillip , Burton Jason , Low Lee-Fay , Loi Samantha M. , Fairhall Anne , Polacsek Meg , Stiles Jay , Muliadi Fenny , Chau Nadia , Scherer Samuel , Ames David , Sousa Tanara Vieira , Dow Briony
Published: December 2021

Background

Home care service providers are increasingly supporting clients living with dementia. Targeted and comprehensive dementia-specific training for home care staff is necessary to meet this need. This study evaluates a training programme delivered to care staff (paid personal carers) of clients living with dementia at home.

Methods

This study is a pragmatic stepped-wedge cluster-randomised controlled trial (SW-CRT). Home care workers (HCWs) from seven home care service providers are grouped into 18 geographical clusters. Clusters are randomly assigned to intervention or control groups. The intervention group receives 7 h of a dementia education and upskilling programme (Promoting Independence Through quality dementia Care at Home [PITCH]) after baseline measures. The control group receives PITCH training 6 months after baseline measures. This approach will ensure that all participants are offered the program. Home care clients living with dementia are also invited to participate, as well as their family carers. The primary outcome measure is HCWs’ sense of competence in dementia care provision.

Discussion

Upskilling home care staff is needed to support the increasing numbers of people living with dementia who choose to remain at home. This study uses a stepped-wedge cluster-randomised trial to evaluate a training programme (PITCH) for dementia care that is delivered to front-line HCWs.

Trial registration

anzctr.org.au; ACTRN12619000251123. Registered on 20 February 2019.
Comparison of extended reality and conventional methods of basic life support training: protocol for a multinational, pragmatic, noninferiority, randomised clinical trial (XR BLS trial)
Authors: Lee Dong Keon , Im Chang Woo , Jo You Hwan , Chang Todd , Song Joo Lee , Luu Cindy , Mackinnon Ralph , Pillai Suresh , Lee Chuen Neng , Jheon Sanghoon , Ahn Soyeon , Won Seung Hyun
Published: December 2021

Background

Conventional cardiopulmonary resuscitation (CPR) training for the general public involves the use of a manikin and a training video, which has limitations related to a lack of realism and immersion. To overcome these limitations, virtual reality and extended reality technologies are being used in the field of medical education. The aim of this study is to explore the efficacy and safety of extended reality (XR)-based basic life support (BLS) training.

Methods

This study is a prospective, multinational, multicentre, randomised controlled study. Four institutions in 4 countries will participate in the study. A total of 154 participants will be randomly assigned to either the XR group or the conventional group stratified by institution and sex (1:1 ratio). Each participant who is allocated to either group will be sent to a separate room to receive training with an XR BLS module or conventional CPR training video. All participants will perform a test on a CPR manikin after the training. The primary outcome will be mean compression depth. The secondary outcome will be overall BLS performance, including compression rate, correct hand position, compression, and full release and hands-off time.

Discussion

Using virtual reality (VR) to establish a virtual educational environment can give trainees a sense of realism. In the XR environment, which combines the virtual world with the real world, trainees can more effectively learn various skills. This trial will provide evidence of the usefulness of XR in CPR education.

Trial registration

ClinicalTrials.gov NCT04736888. Registered on 29 January 2021
Promoting physical activity and health in Hong Kong primary school children through a blended physical literacy intervention: protocol and baseline characteristics of the “Stand+Move” randomized controlled trial
Authors: Li Ming Hui , Sit Cindy Hui Ping , Wong Stephen Heung Sang , Wing Yun Kwok , Ng Ching Kong , Sum Raymond Kim Wai
Published: December 2021

Background

Children predominantly remain sedentary in a traditional classroom. This study aimed to demonstrate the design and baseline characteristics of a three-armed intervention program that targeted enhancements in children’s physical literacy (PL), physical activity (PA), sleep, and executive functions by constructing an active classroom environment in primary schools. The blended approach involved organized PA participation during recess combined with changes to the classroom environment in response to the emphasis on nurturing children’s PL in Hong Kong.

Methods

This blended “Stand + Move” intervention adopted a randomized controlled trial design to investigate its effectiveness in improving health-related aspects. Three groups were compared: (1) PA recess intervention, (2) blended (sit-stand desks and PA recess) experimental, and (3) control groups. In this 13-week intervention (from March to September 2019), 76 students (59.2% girls) were recruited and randomly assigned to the three groups. The primary outcomes were children’s PL and PA. The secondary outcomes were children’s sleep and executive functions.

Results

Baseline data were evaluated. The mean age was 9.6 years [standard deviation = 0.61, range 9.0–12.0]. There were no significant differences between trial arms at baseline concerning any of the outcomes (all P = 0.06–0.89). Overall, 22.4% met the recommended PA guidelines, 36.8% met the sleep guidelines, and 10.5% met both guidelines. Three aspects of executive functions were evaluated: inhibition, executive control, and planning. Over half of the participants reported satisfaction with their perceived sleep quality.

Conclusions

The designed intervention is regarded as an innovative strategy that incorporates sit-stand desks and PA breaks to reconstruct children’s traditional classroom environment. The baseline results suggest that intervention was satisfactory in reducing students’ sitting time and increasing their PA engagement. We demonstrated the benefits of this intervention on children’s PL, various sleep patterns, and executive functions. As expected, the designed intervention changes made to the classroom improved children’s health behaviors, as well as the support from stakeholders at schools and the children’s families. Our results also provided the desired evidence for policy reforms in teaching and learning strategies.

Trial registration

ChiCTR ChiCTR2000035038. Registered on July 29, 2020—retrospectively registered
In-silico analysis reveals druggable single nucleotide polymorphisms in angiotensin 1 converting enzyme involved in the onset of blood pressure
Authors: Udosen Brenda , Soremekun Opeyemi , Ekenna Chinwe , Idowu Omotuyi Olaposi , Chikowore Tinashe , Nashiru Oyekanmi , Fatumo Segun
Published: December 2021

Objective

The Angiotensin 1 converting enzyme (ACE1) gene plays a critical role in regulating blood pressure and thus, it has become a major therapeutic target of antihypertensives. Single nucleotide polymorphisms (SNPs) occurring within a gene most especially at the functional segment of the genes alter the structure–function relationship of that gene.

Results

Our study revealed that five nsSNPs of the ACE1 gene were found to be potentially deleterious and damaging and they include rs2229839, rs14507892, rs12709442, and rs4977 at point mutations P351R, R953Q, I1018T, F1051V, and T1187M. The protein stability predictive tools revealed that all the nsSNPs decreased stability of the protein and the Consurf server which estimates the evolutionary conservation profile of a protein showed that three mutants were in the highly conserved region. In conclusion, this study predicted potential druggable deleterious mutants that can be further explored to understand the pathological basis of cardiovascular disease.
Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer’s disease
Authors: Sprugnoli Giulia , Munsch Fanny , Cappon Davide , Paciorek Rachel , Macone Joanna , Connor Ann , El Fakhri Georges , Salvador Ricardo , Ruffini Giulio , Donohoe Kevin , Shafi Mouhsin M. , Press Daniel , Alsop David C. , Pascual Leone Alvaro , Santarnecchi Emiliano
Published: December 2021

Background

Alzheimer’s disease (AD) is associated with alterations in cortical perfusion that correlate with cognitive impairment. Recently, neural activity in the gamma band has been identified as a driver of arteriolar vasomotion while, on the other hand, gamma activity induction on preclinical models of AD has been shown to promote protein clearance and cognitive protection.

Methods

In two open-label studies, we assessed the possibility to modulate cerebral perfusion in 15 mild to moderate AD participants via 40Hz (gamma) transcranial alternating current stimulation (tACS) administered 1 h daily for 2 or 4 weeks, primarily targeting the temporal lobe. Perfusion-sensitive MRI scans were acquired at baseline and right after the intervention, along with electrophysiological recording and cognitive assessments.

Results

No serious adverse effects were reported by any of the participants. Arterial spin labeling MRI revealed a significant increase in blood perfusion in the bilateral temporal lobes after the tACS treatment. Moreover, perfusion changes displayed a positive correlation with changes in episodic memory and spectral power changes in the gamma band.

Conclusions

Results suggest 40Hz tACS should be further investigated in larger placebo-controlled trials as a safe, non-invasive countermeasure to increase fast brain oscillatory activity and increase perfusion in critical brain areas in AD patients.

Trial registration

Studies were registered separately on ClinicalTrials.gov (NCT03290326, registered on September 21, 2017; NCT03412604, registered on January 26, 2018).
Optimal control for cooperative systems involving fractional Laplace operators
Authors: Serag H. M. , Hyder Abd-Allah , El-Badawy M.
Published: December 2021

In this work, the elliptic $2\times 2$
2
×
2
cooperative systems involving fractional Laplace operators are studied. Due to the nonlocality of the fractional Laplace operator, we reformulate the problem into a local problem by an extension problem. Then, the existence and uniqueness of the weak solution for these systems are proved. Hence, the existence and optimality conditions are deduced.
Weighted differential inequality and oscillatory properties of fourth order differential equations
Authors: Kalybay Aigerim , Oinarov Ryskul , Sultanaev Yaudat
Published: December 2021

In this paper, we investigate the oscillatory properties of two fourth order differential equations in dependence on boundary behavior of its coefficients at infinity. These properties are established based on two-sided estimates of the least constant of a certain weighted differential inequality.
Drastic advancement in nanophotonics achieved by a new dressed photon study
Authors: Sakuma Hirofumi , Ojima Izumi , Ohtsu Motoichi , Kawazoe Tadashi
Published: December 2021

On the very recent advancement of dressed photon studies

A timely review of the emerging new phase of dressed photon (DP) studies, not yet prevailing in the global nanophotonic society, is given in contradistinction to its preceding incipient phase. A new theory on DPs crucially depends on a couple of important elements, namely, the knowledge on quantum field theory (QFT) having infinite degrees of freedom, notably on the micro-macro duality (MMD) theory developed by Ojima, and a newly proposed Clebsch dual (CD) electromagnetic field as a specific implementation of MMD theory. The main aim of the first part of this article after the introduction, the section of “In search of refinement of the theoretical models”, is twofold: to explain plainly, without resorting to mathematical equations, the essence of the highly mathematical contents of MMD theory, which clarifies a problematic aspect of the Schrödinger’s cat thought experiment, and to explain the physical meanings of the CD field.

Preliminary study on the existence of DP light with spin zero

In the section of “Observed “photon cluster” and light field with spin zero”, we briefly report a new intriguing experimental discovery implying the existence of propagating particle-like “quantum DP light” together with a conjecture on its possible theoretical explanation. A perspective on a variety of possible research directions for DPs is then briefly mentioned in the final section.
Dental fluorosis among people and livestock living on Gihaya Island in Lake Kivu, Rwanda
Authors: Habiyakare Theodore , Schurer Janna M. , Poole Barika , Murcott Susan , Migabo Basile , Mardochee Birori , Amuguni J. Hellen , Morgan John P.
Published: December 2021

Background

Dental
fluorosis is caused by prolonged exposure to excessive fluoride during the period of permanent tooth formation and is characterized by tooth discoloration, pitting, and loss of shape. Communities living near Lake Kivu in Western Rwanda exhibit a high prevalence of dental fluorosis; however, data on prevalence and risk factors are scarce.

Methods

This cross sectional, quantitative study used a One Health approach to investigate dental fluorosis prevalence among people and livestock and to measure fluoride content in the environment. In 2018, oral health examinations were conducted to assess the prevalence of fluorosis in children (aged 9 to 15 years), cattle and goats residing on Gihaya Island (Rwanda, East Africa). All children and cattle/goats meeting basic eligibility criteria (e.g., island residence) were invited to participate. Presence and severity of dental fluorosis was categorized according to the Dean’s Fluorosis Index. Samples of local foods, water, soil and grass were collected from communal sources and individual households and analyzed for fluoride content using standard laboratory techniques. Descriptive and binomial analyses (Fisher Exact Test) were used to assess this dataset.

Results

Overall, 186 children and 85 livestock owners (providing data of 125 livestock -23 cattle and 102 goats) participated. Dental fluorosis was recorded in 90.7% of children and 76% of livestock. Moderate to severe fluorosis was observed in 77% children while goats and cattle most often exhibited mild or absent/questionable severity, respectively. Water from Lake Kivu (used primarily for human cooking water and livestock drinking water) contained fluoride levels that were consistently higher than the maximum threshold (1.5 mg/L) recommended by the World Health Organization. Other sources (borehole and rainwater) were within safe limits. All food, soil and grass samples contained fluoride. The highest levels were observed in porridge (0.5 mg/g) and small fishes (1.05 mg/g).

Conclusions

Altogether, dental fluorosis was highly prevalent among children and goats on Gihaya Island with various food and water sources contributing a cumulative exposure to fluoride. An immediate and coordinated response across human, animal and water professionals is needed to reduce fluoride exposure within safe limits for island residents.
Kounis syndrome secondary to nimesulide ingestion: a case report
Authors: Shrimanth Yamasandi Siddegowda , Vemuri Krishna Santosh , Gawalkar Atit A. , Ghosh Soumitra , Vijay Jyothi , Prarthana Thammannagowda , Sihag Bhupendra Kumar
Published: December 2021

Background

Kounis syndrome, also known as "allergic myocardial infarction," is a rare co-occurrence of acute coronary syndrome (ACS) in the setting of hypersensitivity reaction to any agent. Non-steroidal anti-inflammatory drugs (NSAIDs) like are often implicated in causing allergic reactions. Here, we present a case of anterior wall myocardial infarction (AWMI) occurred following angioedema secondary to intake of Nimesulide, not described earlier in literature.

Case presentation

A 45-year-old female developed generalized pruritic, erythematous maculopapular rash, facial puffiness, oral ulcers and hoarseness of voice within few hours following consumption of Nimesulide for fever and body-ache. Due to development of hypotension, electrocardiogram (ECG) was done, which revealed ST elevation in V2–V6, with marked elevation of troponin (TnI) and creatine kinase (CK-MB). He had no chest pain or shortness of breath. Echocardiography showed regional wall motion (RWMA) abnormality in left anterior descending artery (LAD) territory with an ejection fraction of 25%. Coronary angiography showed a complete thrombotic cutoff of LAD, for which Tirofiban infusion was started to decrease thrombus burden. Repeat angiography on next day showed 80% lesion in proximal LAD for which she underwent revascularization with a drug-eluting stent. The patient later showed improvement in cardiac function at 8 months of follow-up.

Conclusions

The occurrence of ACS requiring percutaneous coronary intervention (PCI) in the setting of allergic reactions is rarely reported in the literature. One should be aware of the rare possibility of Kounis syndrome in the setting of hypersensitivity reaction when accompanying features of symptoms suggestive of coronary artery disease co-exists. When indicated, ECG monitoring and cardiac biomarkers in patients with allergic responses help to identify this rare and treatable condition.
Effect of vascular endothelial growth factor gene polymorphisms on disease activity in rheumatoid arthritis
Authors: Sallam Rehab A. , Saad Bassant S. , El Wassefy Mona A. , EL Kady Basma A.
Published: December 2021

Background

The full etiology of RA remains unclear; in addition to the contributions of infectious, hormonal, and environmental factors, several lines of evidence have suggested that the disease has a genetic basis. The VEGF gene is also an independent risk factor for RA severity and correlates with multiple disease parameters, such as disease activity, joint damage, and functional disability. This case-control study aimed to investigate the impact of a common genetic polymorphism in the vascular endothelial growth factor (VEGF) gene on disease activity and synovial lesions in patients with rheumatoid arthritis (RA).

Results

T allele was present in the RA group more frequently (22.5% vs. 10% respectively in controls). The C allele was less frequent in the RA group (77.7% vs. 90% respectively in controls) (P = 0.002). Homozygous genotype (CC) was found in 61.2% of patients and 82.5% of controls, homozygous genotype (TT) in 6.3% of patients, and 2.5% of controls while heterozygous (CT) genotype in 32.5% of patients and 15% of controls (P = 0.011). Grade 1 PDUS was found in 30.6% of CC and 11.5% of CT and not found in TT genotypes. The grade 2 was found in 69.4%, 65.4%, and only 20% of CC, CT, and TT genotypes, respectively. The grade 3 was found in 80% of TT, 23.1% of CT, and none of CC genotypes (P < 0.001).

Conclusion

An association between VEGF gene SNP rs3025039 and increased risk for RA among a sample of Egyptian population was noticed. VEGF gene polymorphism appears to be a potential diagnostic activity indicator and a promising therapeutic target for RA patients.
Person-centred care in psychiatry: a clinical and philosophically informed approach
Authors: Glas Gerrit
Published: December 2021

After many years of mental healthcare reform there is still a lot of unease among patients about healthcare workers’ lack of attention to their daily needs and to the tensions and ambiguities that accompany their attempts to integrate their condition into their lives. Person-centred care is often presented as a solution, but the term refers to many differing approaches and needs further specification depending on the problem it aims to resolve. This article presents and discusses a clinical and philosophically informed approach that flexibly focuses on the person- and context-bound aspects of the patient's condition and on the co-regulatory role of the clinician in the patient's attempt to regulate their condition. This approach is a way of thinking, rather than yet another model. It will be shown how this approach can be integrated in the core curriculum of specialty (residency) training in psychiatry.
Higher Incidence of Metabolic Syndrome in Black Women With Polycystic Ovary Syndrome: A Longitudinal Study
Authors: Lee Iris , Vresilovic Julia , Irfan Maryam , Gallop Robert , Dokras Anuja
Published: December 2021

Context

Cross-sectional studies have identified an increased risk of metabolic syndrome (MetSyn) in women with polycystic ovary syndrome (PCOS), but longitudinal data are limited and primarily include White and European cohorts.

Objective

To compare the longitudinal risk of MetSyn in Black and White women with PCOS and to identify potential factors mediating the risk of MetSyn.

Methods

Longitudinal cohort study with a follow-up of 5.3 years at an academic medical center

of

247 adult women with hyperandrogenic PCOS phenotype with 2 or more visits at least 3 years apart. The main outcome measure was incidence of MetSyn in Black and White women with PCOS.

Results

Using a mixed-effects model over time, the incidence of MetSyn was higher in Black women (45.9 ± 4.74 per 100 person-years) than in White women (31.3 ± 3.03 per 100 person-years) (P < .01) after adjusting for age and medication status. This difference persisted among women under age 30. Among Black women who did not have MetSyn at their prior visit, 28.0% had MetSyn at the next visit, compared with 12.1% of White women after adjusting for age and medication status (P < .01). In both races, the model-based estimated rates of MetSyn increased significantly with increase in body mass index and free testosterone.

Conclusion

We describe a persistent higher incidence of MetSyn in Black than in White women with PCOS. In addition to early cardiometabolic screening at the time of diagnosis, our findings highlight the need for ongoing and frequent screening in this population.
Right Ventricular Outflow Tract Obstruction in the Intensive Care Unit: A Case Report of 2 Patients
Authors: Zeng Yu Hao , Calderone Alexander , Beaubien-Souligny William , Aldred Matthew P. , Couture Etienne J. , Hammoud Ali , Potes Cristhian , Lamarche Yoan , Denault André Y.
Published: December 2021

Right ventricular outflow tract obstruction (RVOTO) is a rare cause of hemodynamic instability in the intensive care unit (ICU) after cardiac surgery. We report the first cases of RVOTO diagnosed in the ICU using continuous right ventricular pressure waveform monitoring. Our 2 cases reflect both mechanical and dynamic causes of obstruction, each of which require different approaches to treatment. Inotrope use can exacerbate RVOTO caused by dynamic etiology, whereas surgery is usually the treatment of choice for mechanical obstructions. Inability to recognize RVOTO or the correct etiology can lead to hemodynamic compromise and poor outcomes.
Analysis of the H-Ras mobility pattern in vivo shows cellular heterogeneity inside epidermal tissue
Authors: Gora Radoslaw J. , de Jong Babette , van Hage Patrick , Rhiemus Mary Ann , van Steenis Fjodor , van Noort John , Schmidt Thomas , Schaaf Marcel J. M.
Published: December 2021

Developments in single-molecule microscopy (SMM) have enabled imaging individual proteins in biological systems, focusing on the analysis of protein mobility patterns inside cultured cells. In the present study, SMM was applied in vivo, using the zebrafish embryo model. We studied dynamics of the membrane protein H-Ras, its membrane-anchoring domain, C10H-Ras, and mutants, using total internal reflection fluorescence microscopy. Our results consistently confirm the presence of fast- and slow-diffusing subpopulations of molecules, which confine to microdomains within the plasma membrane. The active mutant H-RasV12 exhibits higher diffusion rates and is confined to larger domains than the wild-type H-Ras and its inactive mutant H-RasN17. Subsequently, we demonstrate that the structure and composition of the plasma membrane have an imperative role in modulating H-Ras mobility patterns. Ultimately, we establish that differences between cells within the same embryo largely contribute to the overall data variability. Our findings agree with a model in which the cell architecture and the protein activation state determine protein mobility, underlining the importance of SMM imaging for studying factors influencing protein dynamics in an intact living organism.

This article has an associated First Person interview with the first author of the paper.
A versatile tRNA modification-sensitive northern blot method with enhanced performance
Authors: Khalique Abdul , Mattijssen Sandy , Maraia Richard J.
Published: December 2021

The 22 mitochondrial and ∼45 cytosolic tRNAs in human cells contain several dozen different post-transcriptional modified nucleotides such that each carries a unique constellation that complements its function. Many tRNA modifications are linked to altered gene expression, and deficiencies due to mutations in tRNA modification enzymes (TMEs) are responsible for numerous diseases. Easily accessible methods to detect tRNA hypomodifications can facilitate progress in advancing such molecular studies. Our laboratory developed a northern blot method that can quantify relative levels of base modifications on multiple specific tRNAs ∼10 yr ago, which has been used to characterize four different TME deficiencies and is likely further extendable. The assay method depends on differential annealing efficiency of a DNA-oligo probe to the modified versus unmodified tRNA. The signal of this probe is then normalized by a second probe elsewhere on the same tRNA. This positive hybridization in the absence of modification (PHAM) assay has proven useful for i6A37, t6A37, m3C32, and m2,2G26 in multiple laboratories. Yet, over the years we have observed idiosyncratic inconsistency and variability in the assay. Here we document these for some tRNAs and probes and illustrate principles and practices for improved reliability and uniformity in performance. We provide an overview of the method and illustrate benefits of the improved conditions. This is followed by data that demonstrate quantitative validation of PHAM using a TME deletion control, and that nearby modifications can falsely alter the calculated apparent modification efficiency. Finally, we include a calculator tool for matching probe and hybridization conditions.