bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged postoperative length of stay may be a valuable marker for susceptibility to relapse beyond established risk factors in patients with stage III colon cancer
Authors: Emland Frans , Taflin Helena , Carlsson Göran , Ljungman David , Lindskog Elinor Bexe
Published: September 2022

Background

Delay from surgery to adjuvant chemotherapy causes impaired survival among patients undergoing radical resection for stage III colon cancer, and the underlying mechanism for this is incompletely clarified. It is established that prolonged postoperative hospital length of stay (LOS) is associated with delayed initiation of the adjuvant treatment driving the assumption that prolonged LOS is prognostically unfavorable due to this fact and case mix factors. We hypothesize that prolonged LOS after surgery is a valuable marker for susceptibility to relapse that is not detected in established prognostic factors and, alone, associated with a shorter disease-free survival (DFS).

Materials and methods

A total of 690 consecutive patients undergoing elective radical resection for stage III colon cancer in 2000–2015 were identified in a prospective detailed facility database. Univariate and multivariate analyses were performed using Cox proportional hazards model in the evaluation of LOS as an independent prognostic factor.

Results

Short postoperative LOS, low comorbidity, and few complications were associated with longer DFS (p < 0.01). Fewer patients in the short and intermediate LOS groups had a relapse in their disease (28% and 33%, respectively), compared to the patients with longer LOS (40%, p < 0.05). LOS was a prognostic factor for DFS in the unadjusted univariate model (HR 1.04 per unit change) and remained statistically significant in the adjusted multivariate analysis, with a HR of 1.03 per hospital day (p < 0.01).

Conclusions

Postoperative LOS independently correlates with the risk of recurrence and DFS, regardless of if adjuvant chemotherapy is given, along with the factors such as age, comorbidity, complications, and tumor features. We propose a further investigation into the causal mechanisms based on tumor and host biology linking LOS to DFS beyond established risk factors.
Natural history comparison study to assess the efficacy of elamipretide in patients with Barth syndrome
Authors: Hornby Brittany , Thompson William Reid , Almuqbil Mohammed , Manuel Ryan , Abbruscato Anthony , Carr Jim , Vernon Hilary J.
Published: September 2022

Background

Natural history studies are increasingly recognized as having an important role in drug development for rare diseases. A phase 3, observational, retrospective, and non-interventional study was designed to establish a natural history control (NHC) cohort of patients with Barth syndrome (BTHS) to provide further analysis of the efficacy of elamipretide observed in an open-label extension (OLE) phase of the TAZPOWER trial, a clinical trial that tested the efficacy of 40 mg daily of elamipretide in patients with BTHS.

Methods

This was a retrospective, non-interventional study. A propensity score model was used to compare elamipretide-treated patients and NHCs. The analysis included 8 patients from the TAZPOWER OLE and 19 untreated NHCs (including 12 with serial echocardiographic assessments).

Results

For the 6-min walk test (6MWT, primary endpoint), the least squares (LS) mean difference between groups was 79.7 m (P = 0.0004) at week 64 and 91.0 m (P = 0.0005) at week 76 in favor of elamipretide. Significant improvements in muscle strength (secondary endpoint), as assessed by handheld dynamometry (HHD) were also observed with elamipretide, with LS mean differences of 40.8 Newtons at 64 weeks (P = 0.0002) and 56.7 Newtons at 76 weeks (P = 0.0005). Patients continuously treated with elamipretide also experienced statistically significant improvements in other secondary endpoints (i.e., 5 times sit-to-stand [5XSST], multi-domain responder index [MDRI]). The functional improvements were robust to sensitivity analyses. Left ventricular stroke volume increased from baseline in patients with elamipretide but decreased in NHCs.

Conclusions

Overall, the study established a NHC for use in assessing the efficacy of therapeutic interventions in patients with BTHS and the results suggest that elamipretide may improve natural history of BTHS at least in part by attenuating the natural decline in heart function and provide meaningful improvements in heart function and functional capacity in patients with BTHS compared to NHCs.

Highlights

A matched Natural History Control (NHC) was used to evaluate elamipretide in BTHS

Elamipretide may improve natural history of BTHS by attenuating natural decline in heart function

Elamipretide was associated with meaningful clinical improvements in skeletal muscle and cardiovascular parameters that were not observed in NHCs

The study established a NHC for use in assessing the efficacy of therapeutic interventions in BTHS
Clinical phenotypes and genetic features of hereditary transthyretin amyloidosis patients in China
Authors: He Xinyue , Tian Zhuang , Guan Hongzhi , Zhang Shuyang
Published: September 2022

Background

Hereditary transthyretin amyloidosis (hATTR) is a progressive and fatal disease with heterogenous clinical presentations, limited diagnosis and poor prognosis. This retrospective analysis study aimed to report the genotypes and phenotypes of herediary transthyretin amyloidosis (hATTR) in Chinese through a systematic review of published literature.

Methods

The systematic review included structured searches of peer-reviewed literature published from 2007 to 2020 of following online reference databases: PubMed, Web of Science and the literature database in China. Extracted data included sample size, personal information (sex, age, natural course, family history), mutation type, clinical milestones and reason of death.

Results

We described 126 Chinese patients with hereditary transthyretin amyloidosis identified through a systematic review of 30 studies. The most common genotype in the Chinese population was Gly83Arg (25, 19.8%), which most likely presented visual and neurological abnormalities without reported death. The second and third most common genotypes were Val30Met (20, 15.9%) and Val30Ala (10, 7.9%). Peripheral neurological manifestations (91, 72%) were dominant in 126 patients. The followed manifestation was autonomic neurological abnormalities (73, 58%). Half of the cases were reported to have visual disorders, and nearly one-third of the cases presented cardiac abnormalities. Among all 126 reported patients, 46.03% were classified as neurological type, 30.16% as mixed type and only 2.38% as cardiac type. In addition. Chinese patients were mostly early onset, with age of onset at 41.8 (SD: 8.9) years, and the median time from onset to death was 7.5 [IQR: 5.3] years. Patients with cardiac involvement had a shorter survival duration (log Rank (Mantel-Cox), χ2 = 26.885, P < 0.001).

Conclusions

This study focused on 126 Chinese hATTR patients obtained from a literature review. A total of 26 kinds of TTR mutations were found and the most common one was Gly83Arg. As for phenotype, 46.03% were classified as neurological type, 30.16% as mixed type and only 2.38% as cardiac type. Chinese hATTR patients were mostly early onset (AO 41.8 years), and the median time from onset to death was 7.5 years.
Health insurance literacy and health services access barriers in Niemann–Pick disease: the patient and caregiver voice
Authors: Diaz George A. , Crowe Joslyn , Hopkin Justin
Published: September 2022

Background

Major challenges to health care access include low health insurance literacy, prohibitive costs, and insurance barriers. Niemann–Pick disease (NPD), comprising acid sphingomyelinase deficiency (ASMD) and Niemann–Pick type C (NPC), is a group of rare, autosomal recessive, highly heterogeneous, neurovisceral, life-threatening, relentlessly progressive lysosomal disorders. Patients experience debilitating systemic and neurological symptoms and substantial emotional and financial stress. Currently, these multifaceted disorders are managed symptomatically as there are no approved therapies. Given the considerable disease burden of NPD, timely access to quality health care is paramount for improving outcomes in these life-threatening disorders. Understanding health insurance literacy and access challenges among patients with NPD and their caregivers is a first step to overcoming treatment barriers.

Results

Patients from the Niemann–Pick community participated in a health insurance literacy survey and follow-up telephone interviews on perceived access challenges. Of the 79 respondents who completed the survey, 67 participated in interviews. All respondents had stable health insurance coverage. However, 61% of respondents were unaware of Medicaid waivers and did not avail of them. Overall, 50% of respondents with childhood onset NPC selected Medicaid/Medicare and private insurance; 35% utilized Medicaid waivers. Most respondents with ASMD had private insurance only. Although the Niemann–Pick community demonstrated greater health insurance literacy than the general population, knowledge gaps exist in calculating insurance coverage, out-of-pocket maximums, and defining a formulary. The most frequently cited access burden was the process of obtaining medical care and services. Among respondents with ASMD, the greatest access burden was fear of unavailability of or access to medications and treatment. Access challenges adversely impacted patients’ mental health and exacerbated physical symptoms. Delays and denials in obtaining essential medication, equipment, and services contributed to disease progression. Caregivers faced burnout and often questioned the utility of their advocacy.

Conclusions

This study identified knowledge gaps in health insurance literacy and challenges to access medication and health care services among individuals impacted by NPD. Patients and caregivers need the knowledge and skills to navigate a complicated health care system, understand their rights to medication and services and, ultimately, benefit from improved outcomes, especially in a post–drug approval era.
An international study of caregiver-reported burden and quality of life in metachromatic leukodystrophy
Authors: Sevin Caroline , Barth Magalie , Wilds Alexandra , Afriyie Abena , Walz Markus , Dillon Annamarie , Howie Kenneth , Pang Francis
Published: September 2022

Background

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder caused by mutations in the arylsulfatase A gene. Until now, there has been little information on the burden of MLD on patients and their caregivers. This multinational study aims to quantify caregiver-related impacts of MLD across several key domains including symptoms, treatment burden, time investment, social and emotional well-being, and professional and financial impact.

Results

Data were collected through moderator-assisted web survey and telephone interviews. The survey was developed with extensive input from clinical experts and MLD patient advocacy groups. The EQ-5D-5L questionnaire was administered during follow-up interviews. The total sample consisted of parents of MLD patients in the US (n = 10), France (n = 10), Germany (n = 6), UK (n = 5), Belgium (n = 1), and Norway (n = 2). The impact of MLD is evident from the EQ-5D-5L scores, which indicate utility values for caregivers below respective national population norms and a higher proportion of caregivers reporting problems with anxiety/depression. Time involved for care was demonstrated by a mean of 4.1 inpatient and 29.6 outpatient hospital visits in the previous 12-month period. These commitments place stress on familial relationships with 50% of caregivers reporting their child’s MLD diagnosis had negatively impacted their relationship with their spouse/partner. Professionally, 76.5% of caregivers stopped working or switched to part-time employment following their child’s MLD diagnosis, and most acknowledged caring for their child had affected their potential for career progression or promotion. Differences are also observed based on late infantile versus juvenile onset MLD, time since diagnosis, and for transplanted patients versus those who received palliative care only.

Conclusions

This multinational study demonstrates that MLD consistently negatively affects many aspects of caregivers’ lives including health, relationships, and professional status, irrespective of location. We expect that the results of this study are generalizable to other countries. This study enhances our understanding of MLD caregiver impacts, which could improve patient care and assist in identifying support for individuals with MLD and their families.
Clinical efficacy of mandibular complete dentures with a resilient liner: study protocol for a multicenter randomized controlled trial
Authors: Kimoto Katsuhiko , Kimoto Suguru , Hoshi Noriyuki , Sato Yusuke , Yoneyama Yoshikazu , Takebe Jun , Ichikawa Tetsuo , Murata Hiroshi , Nishimura Masahiro , Minakuchi Shunsuke , Kawai Yasuhiko
Published: September 2022

Background

During restoration of poorly fitting complete dentures (CDs) in edentulous patients, liners are used to reconstruct the concave surfaces of CDs with a new base material. These relining materials are classified into resilient liners (RLs) and non-resilient liners (NRLs), but the clinical effects of these liners and their selection criteria remain unclear. The purpose of this study is to evaluate the clinical efficacy of relining mandibular CDs using RL and NRL and to conduct a follow-up study.

Methods

The study is currently being conducted at eight centers, and a parallel-group randomized controlled trial (RCT) is underway. One hundred thirty-two edentulous patients with poorly fitting mandibular CDs will be assigned to two groups based on whether they will receive RL or NRL. Participants will have an RL or NRL applied for relining their CDs using an indirect method of dynamic impressions. Data will be recorded at 1 week and 3, 6, and 12 months after denture delivery. The primary outcome will be assessment of the patients’ general satisfaction by using a 100-mm visual analog scale (VAS). Secondary outcomes will be measured as patient-reported outcomes, including food intake status and oral hygiene-related quality of life. Masticatory performance and the number of sore spots on the oral mucosa will also be recorded. Comparisons between the two groups and within-subject comparisons of pre- and post-intervention measurements will be conducted.

Discussion

For dentists and prosthetic researchers in Japan, this RCT will provide information on the clinical efficacy of RL materials in comparison to RNL in CD wearers. The new evidence regarding the use of RL materials in an aging population will also be useful to dentists in other countries in their routine clinical practice.

Trial registration

This clinical trial has been registered at the University Hospital Medical Information Network (UMIN) Center (UMIN000041950).
Efficacy and safety of EXOWALK® on electromechanical-assisted gait training: study protocol for randomized controlled trial
Authors: Lim Chi-Yeon , Ko Mun Jung , Lee Jin Won , Bok Soo Kyung , Paik Nam-Jong , Nam Yeon Gyo , Kwon Bum Sun
Published: September 2022

Background

High-intensity repetitive task-specific practice might be the most effective strategy to promote motor recovery after stroke, and electromechanical-assisted gait training represents one of the treatment options. However, there is still difficulty in clarifying the difference between conventional gait training and electromechanically assisted gait training.

Methods

The study is a multicenter, randomized, parallel-group clinical trial for stroke patients. Three clinical research centers in Korea (Dongguk University Ilsan Hospital, Chungnam National University Hospital, and Seoul National University Bundang Hospital) will participate in the clinical trial and 144 stroke patients will be registered. Enrolled patients are assigned to two groups, an experimental group and a control group, according to a randomization table. In addition, patients are treated for half an hour (one session) five times a week for 4 weeks. Both groups carry out basic rehabilitation (central nervous system development therapy and strength exercise) and the experimental group executes robotic walking rehabilitation treatment, and the control group executes conventional gait rehabilitation treatment. The primary endpoint variable is the Functional Ambulation Category (FAC) that determines the degree of independent walking and is measured before, after, and after 4 weeks of treatment. Secondary endpoint variables are 11 variables that take into account motor function and range, measured at the same time as the primary endpoint variable.

Discussion

There are still insufficient data on the effectiveness of electromechanical-assisted gait training for stroke patients and large-scale research is lacking. Thus, the research described here is a large-scale study of stroke patients that can supplement the limitations mentioned in other previous studies. In addition, the clinical studies described here include physical epidemiological analysis parameters that can determine walking ability. The results of this study can lead to prove the generalizable effectiveness and safety of electromechanical-assisted gait training with EXOWALK®.

Trial registration

Clinical Research Information Service (CRIS), Republic of Korea KCT0003411, Registered on 30 October 2018
Educational interventions to improve women’s preventive behavior of sexually transmitted infections (STIs): study protocol for a randomized controlled trial
Authors: Juyani Afsaneh Karami , Zarei Fatemeh , Niknami Shamsodin , Haydarni Alireza , Maasoumi Raziyeh
Published: September 2022

Background

Sexually active women aged 18 to 48 are within the population at risk for acquiring sexually transmitted infections. Some STIs can cause serious complications in women’s reproductive health. Accordingly, this practical randomized trial aims to evaluate the effect of an interventional education based on the ISD model on improving preventive behaviors for Iranian women.

Methods

Women aged 18–48 years that refer to Tehran Municipality Health Houses will be invited to join the study. Recruitment will continue until a sample of 150 women participants. The study will be conducted using a mixed-methods protocol in three phases. In the first phase, women’s educational and learning needs about STIs will be identified using a qualitative approach. In the second phase, the results from the qualitative approach will be used to design a training program based on an ISD model. The educational intervention will be performed in the third phase. Participants will be randomly allocated into two groups: (1) the intervention group and (2) the control group. Data will be collected using STI Four-Scale of Preventive Behaviors at baseline, immediately, 1-month, and 3-month follow-up assessments. The impact of the intervention on the promotion of preventive behaviors from STIs will then be evaluated.

Discussion

This study provides an educational program for empowering and promoting behaviors that prevent STIs. If the designed interventions in the present study are effective, it has practical potential to be generalized for Iranian women at risk of STIs.

Trial registration

ClinicalTrials.govIRCT20200602047638N1. Registered on 22 May 2021 with the IRCTID, V1.0.
Opening the Conversation: study protocol for a Phase III trial to evaluate a couple-based intervention to reduce reproductive and sexual distress among young adult breast and gynecologic cancer survivor couples
Authors: Gorman Jessica R. , Lyons Karen S. , Harvey S. Marie , Acquati Chiara , Salsman John M. , Kashy Deborah A. , Drizin Julia H. , Smith Ellie , Flexner Lisa M. , Hayes-Lattin Brandon , Reese Jennifer B.
Published: September 2022

Background

Reproductive and sexual health (RSH) concerns are common and distressing for young adults diagnosed with breast and gynecologic cancer and their partners. This study evaluates the efficacy of a virtual couple-based intervention called Opening the Conversation (OC). The OC intervention is grounded in theory and evidence-based practice and was adapted to improve coping and communication specifically in relation to RSH concerns after cancer.

Methods

This Phase III trial is conducted in a fully remote setting and enrolls young adult couples (current age 18–44 years) with a history of breast or gynecologic cancer (stage 1–4, diagnosed under age 40) within the past 6 months to 5 years. Eligible dyads are recruited from across the USA. The target sample size is 100 couples. Dyads are randomly assigned to receive either the 5-session OC intervention or a 4-session active control intervention (Side by Side). The primary outcomes are change in reproductive distress and sexual distress. Secondary outcomes include communication about reproductive concerns, communication about sexual concerns, depressive symptoms, sexual function, relationship quality, relationship intimacy, sexual satisfaction, self-efficacy to communicate about sex and intimacy, and quality of life. An exploratory aim examines whether dyadic coping and communication quality mediate intervention effects on survivors’ and partners’ reproductive distress or sexual distress. Self-report outcome measures are assessed for both groups at baseline (T1), 2 weeks post-treatment (T2), and 3 months post-treatment (T3).

Discussion

Despite the importance of RSH for quality of life for young adult cancer survivors and their partners, evidence-based interventions that help couples navigate RSH concerns are lacking. This randomized controlled trial will determine the efficacy of a novel couple-based intervention to reduce distress related to RSH concerns for younger couples after breast or gynecologic cancer, in comparison to an active control intervention.

Trial registration

ClinicalTrials.gov NCT04806724. Registered on Mar 19, 2021.
Optimum flux rerouting for efficient production of naringenin from acetate in engineered Escherichia coli
Authors: Kim Dong Hwan , Hwang Hyun Gyu , Jung Gyoo Yeol
Published: September 2022

Background

Microbial production of naringenin has received much attention owing to its pharmaceutical applicability and potential as a key molecular scaffold for various flavonoids. In the microbial fermentation, a cheap and abundant feedstock is required to achieve an economically feasible bioprocess. From this perspective, utilizing acetate for naringenin production could be an effective strategy, with the advantages of both low-cost and abundant feedstock. For the efficient production of naringenin using acetate, identification of the appropriate regulatory node of carbon flux in the biosynthesis of naringenin from acetate would be important. While acetyl-CoA is a key precursor for naringenin production, carbon flux between the TCA cycle and anaplerosis is effectively regulated at the isocitrate node through glyoxylate shunt in acetate metabolism. Accordingly, appropriate rerouting of TCA cycle intermediates from anaplerosis into naringenin biosynthesis via acetyl-CoA replenishment would be required.

Results

This study identified the isocitrate and oxaloacetate (OAA) nodes as key regulatory nodes for the naringenin production using acetate. Precise rerouting at the OAA node for enhanced acetyl-CoA was conducted, avoiding extensive loss of OAA by fine-tuning the expression of pckA (encoding phosphoenolpyruvate carboxykinase) with flux redistribution between naringenin biosynthesis and cell growth at the isocitrate node. Consequently, the flux-optimized strain exhibited a significant increase in naringenin production, a 27.2-fold increase (with a 38.3-fold increase of naringenin yield on acetate) over that by the unoptimized strain, producing 97.02 mg/L naringenin with 21.02 mg naringenin/g acetate, which is a competitive result against those in previous studies on conventional substrates, such as glucose.

Conclusions

Collectively, we demonstrated efficient flux rerouting for maximum naringenin production from acetate in E. coli. This study was the first attempt of naringenin production from acetate and suggested the potential of biosynthesis of various flavonoids derived from naringenin using acetate.
Hypnosis for pain and anxiety management in cognitively impaired older adults undergoing scheduled lumbar punctures: a randomized controlled pilot study
Authors: Courtois-Amiot Pauline , Cloppet-Fontaine Anaïs , Poissonnet Aurore , Benit Elodie , Dauzet Muriel , Raynaud-Simon Agathe , Paquet Claire , Lilamand Matthieu
Published: September 2022

Background

Core cerebrospinal fluid (CSF) amyloid and tau biomarker assessment has been recommended to refine the diagnostic accuracy of Alzheimer’s disease. Lumbar punctures (LP) are invasive procedures that might induce anxiety and pain. The use of non-pharmacological techniques must be considered to reduce the patient’s discomfort, in this setting. The objective of this study was to examine the efficacy of hypnosis on anxiety and pain associated with LP.

Methods

A monocentric interventional randomized-controlled pilot study is conducted in a university geriatric day hospital. Cognitively impaired patients aged over 70 were referred for scheduled LP for the diagnostic purpose (CSF biomarkers). The participants were randomly assigned either to a hypnosis intervention group or usual care. Pain and anxiety were both self-assessed by the patient and hetero-evaluated by the operator.

Results

We included 50 cognitively impaired elderly outpatients (women 54%, mean age 77.2 ± 5.0, mean Mini-Mental State Examination score 23.2 ± 3.5). Hypnosis was significantly associated with reduced self-assessed (p < 0.05) and hetero-assessed anxiety (p < 0.01). Hetero-evaluated pain was significantly lower in the hypnosis group (p < 0.05). The overall perception of hypnosis was safe, well-accepted, and feasible in all the participants of the intervention group with 68% perceiving the procedure as better or much better than expected.

Conclusions

This pilot study suggested that hypnosis was feasible and may be used to reduce the symptoms of discomfort due to invasive procedures in older cognitively impaired patients. Our results also confirmed the overall good acceptance of LP in this population, despite the usual negative perception.

Trial registration

ClinicalTrials.gov NCT04368572. Registered on April 30, 2020.
Biological characteristics and pulp regeneration potential of stem cells from canine deciduous teeth compared with those of permanent teeth
Authors: Ziauddin S. M. , Nakashima Misako , Watanabe Hideto , Tominaga Michiyo , Iohara Koichiro
Published: September 2022

Background

Clinical studies have demonstrated that dental pulp stem cells isolated from permanent teeth (PT-DPSCs) are safe and efficacious for complete pulp regeneration in mature pulpectomized permanent teeth with complete apical closure. Moreover, dental pulp stem cells from deciduous teeth (DT-DPSCs) have also been shown to be useful for pulp regenerative cell therapy of injured immature permanent teeth. However, direct comparisons of the pulp regenerative potential of DT-DPSCs and PT-DPSCs from the same individual have not been performed. This study aimed to compare the differences in stem cell properties and pulp regenerative potential of DT-DPSCs and PT-DPSCs of identical origin.

Methods

DT-DPSCs and PT-DPSCs were isolated from the same individual dogs at 4 months and 9 months of age, respectively. The expression of cell surface antigen markers, proliferation and migration activities, and gene expression of stem cell markers, angiogenic/neurotrophic factors and senescence markers were compared. The effects of conditioned medium (CM) derived from these cells on cellular proliferation, migration, angiogenesis, neurite outgrowth and immunosuppression were also compared. Autologous transplantation of DT-DPSCs or PT-DPSCs together with G-CSF was performed to treat pulpectomized teeth in individual dogs. The vascularization and reinnervation of the regenerated pulp tissues were qualitatively and quantitatively compared between groups by histomorphometric analyses.

Results

The rates of positive CXCR4 and G-CSFR expression in DT-DPSCs were significantly higher than those in PT-DPSCs. DT-DPSCs migrated at a higher rate with/without G-CSF and exhibited increased expression of the stem cell markers Oct3/4 and CXCR4 and the angiogenic factor VEGF and decreased expression of the senescence marker p16 than PT-DPSCs. DT-DPSC-derived CM promoted increased cell proliferation, migration with G-CSF, and angiogenesis compared with PT-DPSC-derived CM; however, no difference was observed in neurite outgrowth or immunosuppression. The regenerated pulp tissues in the pulpectomized teeth were quantitatively and qualitatively similar between the DT-DPSCs and PT-DPSCs transplant groups.

Conclusions

These results demonstrated that DT-DPSCs could be a potential clinical alternative to PT-DPSCs for pulp regenerative therapy. DT-DPSCs can be preserved in an individual cell bank and used for potential future pulp regenerative therapy before the supply of an individual’s own sound discarded teeth has been exhausted.
The expression of GapA and CrmA correlates with the Mycoplasma gallisepticum in vitro infection process in chicken TOCs
Authors: Rüger Nancy , Szostak Michael P. , Rautenschlein Silke
Published: September 2022

Mycoplasma (M.) gallisepticum is the most pathogenic mycoplasma species in poultry. Infections cause mild to severe clinical symptoms associated with respiratory epithelial lesion development. Adherence, biofilm formation, and cell invasion of M. gallisepticum contribute to successful infection, immune evasion, and survival within the host. The important M. gallisepticum membrane-bound proteins, GapA and CrmA, are key factors for host cell interaction and the bacterial life-cycle, including its gliding motility, although their precise role in the individual infection step is not yet fully understood. In this study, we investigated the correlation between the host–pathogen interaction and the GapA/CrmA expression in an environment that represents the natural host’s multicellular compartment. We used an in vitro tracheal organ culture (TOC) model, allowing the investigation of the M. gallisepticum variants, Rlow, RCL1, RCL2, and Rhigh, under standardised conditions. In this regard, we examined the bacterial adherence, motility and colonisation pattern, host lesion development and alterations of mucociliary clearance. Compared to low virulent RCL2 and Rhigh, the high virulent Rlow and RCL1 were more efficient in adhering to TOCs and epithelium colonisation, including faster movement from the cilia tips to the apical membrane and subsequent cell invasion. RCL2 and Rhigh showed a more localised invasion pattern, accompanied by significantly fewer lesions than Rlow and RCL1. Unrelated to virulence, comparable mucus production was observed in all M. gallisepticum infected TOCs. Overall, the present study demonstrates the role of GapA/CrmA in virulence factors from adherence to colonisation, as well as the onset and severity of lesion development in the tracheal epithelium.
scMTD: a statistical multidimensional imputation method for single-cell RNA-seq data leveraging transcriptome dynamic information
Authors: Qi Jing , Sheng Qiongyu , Zhou Yang , Hua Jiao , Xiao Shutong , Jin Shuilin
Published: September 2022

Background

Single-cell RNA sequencing (scRNA-seq) provides a powerful tool to capture transcriptomes at single-cell resolution. However, dropout events distort the gene expression levels and underlying biological signals, misleading the downstream analysis of scRNA-seq data.

Results

We develop a statistical model-based multidimensional imputation algorithm, scMTD, that identifies local cell neighbors and specific gene co-expression networks based on the pseudo-time of cells, leveraging information on cell-level, gene-level, and transcriptome dynamic to recover scRNA-seq data. Compared with the state-of-the-art imputation methods through several real-data-based analytical experiments, scMTD effectively recovers biological signals of transcriptomes and consistently outperforms the other algorithms in improving FISH validation, trajectory inference, differential expression analysis, clustering analysis, and identification of cell types.

Conclusions

scMTD maintains the gene expression characteristics, enhances the clustering of cell subpopulations, assists the study of gene expression dynamics, contributes to the discovery of rare cell types, and applies to both UMI-based and non-UMI-based data. Overall, scMTD’s reliability, applicability, and scalability make it a promising imputation approach for scRNA-seq data.
Genetics of type 2 diabetes mellitus in Indian and Global Population: A Review
Authors: Joseph Anjaly , Thirupathamma Maradana , Mathews Elezebeth , Alagu Manickavelu
Published: September 2022

Background

Non-communicable diseases such as cardiovascular diseases, respiratory diseases and diabetes contribute to the majority of deaths in India. Public health programmes on non-communicable diseases (NCD) prevention primarily target the behavioural risk factors of the population. Hereditary is known as a risk factor for most NCDs, specifically, type 2 diabetes mellitus (T2DM), and hence, understanding of the genetic markers of T2DM may facilitate prevention, early case detection and management.

Main body

We reviewed the studies that explored marker–trait association with type 2 diabetes mellitus globally, with emphasis on India. Globally, single nucleotide polymorphisms (SNPs) rs7903146 of Transcription Factor 7-like 2 (TCF7L2) gene was common, though there were alleles that were unique to specific populations. Within India, the state-wise data were also taken to foresee the distribution of risk/susceptible alleles. The findings from India showcased the common and unique alleles for each region.

Conclusion

Exploring the known and unknown genetic determinants might assist in risk prediction before the onset of behavioural risk factors and deploy prevention measures. Most studies were conducted in non-representative groups with inherent limitations such as smaller sample size or looking into only specific marker–trait associations. Genome-wide association studies using data from extensive prospective studies are required in highly prevalent regions worldwide. Further research is required to understand the singular effect and the interaction of genes in predicting diabetes mellitus and other comorbidities.
The insulin-like growth factor and its players: their functions, significance, and consequences in all aspects of ovarian physiology
Authors: Afradiasbagharani Parivash , Hosseini Elham , Allahveisi Azra , Bazrafkan Mahshid
Published: September 2022

Background

Insulin-like growth factor (IGF) has unique and well-known functions in female fertility, according to documents reporting improved yield of oocytes, reinforced quality of the embryo, and enhanced live births with simultaneous reduction of miscarriage. However, there is no detailed information on the bio-mechanisms linking such clinical differences.

Main body

IGF and its receptors are expressed in a variety of tissues in the reproductive system such as granulosa cells, oocytes, and theca cells. Hence, the development of female gametes may be directly regulated by IGF, thereby affecting gamete quality and so its competence for implantation. IGF is a central player in changing the fate of cells during survival and proliferation through the modulation of leading signaling pathways, including Jak/STAT, MAP kinase/ERK, and PI3K/Akt, and subsequent impacts on steroidogenesis and cell division.

Conclusion

The current review aims to scrutinize the performance of IGF to regulate the normal ovarian, and its impacts on cell signaling pathways and resulting alterations in steroidogenesis and cell proliferation. The function of IGF and its receptor has been reviewed in female fertility at both molecular and biochemical levels.
Stability analysis of elastomeric bearings in bridge structures
Authors: Leblouba Moussa
Published: September 2022

Elastomeric bearings (EB) and lead-rubber bearings (LRB) are used in bridge structures to reduce vehicle vibrations, wind loads, and earthquakes. Therefore, studying their stability is crucial to ensuring the stability of the bridge system itself. Building upon previously proposed linear and partially nonlinear models, two fully nonlinear models suitable for EBs and LRBs are proposed in this paper. The models are developed to adequately account for the interaction between the horizontal and vertical loads and their effect on the bearing’s performance. This study considers that the horizontal and vertical loads do not always act in isolation and that their interaction can significantly affect the bearing’s overall behavior and stability. Comparisons with experiments demonstrated that the models could accurately replicate the behavior of seismic isolators. Additionally, analytical models are developed to predict the horizontal and vertical stiffnesses as a function of the critical buckling load. The two mathematical models can readily be incorporated into open-source structural analysis software, such as OpenSees.
Pharmacological treatment of comorbid posttraumatic stress disorder in patients with bipolar disorder
Authors: Hendriks S. , Goossens P.
Published: September 2022

Introduction

The lifetime prevalence of comorbid posttraumatic stress disorder (PTSD) in patients with bipolar disorder (BD) is approximately 20%. Guidelines for BD give adequate pharmacological treatment options when there is a ‘pure’ bipolar disorder but lack of treatment options when there is a comorbid disorder present.

Objectives

The present study aimed to review the pharmacological treatment options for comorbid PTSD in patients with BD.

Methods

Literature research was conducted via PubMed, Embase and the Cochrane Library. Search terms included ‘bipolar disorder’, ‘posttraumatic stress disorder’, ‘PTSD’, ‘pharmacotherapy’ and ‘treatment’. Relevant studies were reviewed.

Results

No randomized controlled trials have been conducted in patients with bipolar disorder and comorbid PTSD. Most studies included open-label studies and case-reports. No convincing scientific evidence for pharmacological treatment of comorbid PTSD in patients with BD was found. Selective serotonin reuptake inhibitors (SSRIs) are effective in the treatment of PTSD. However, SSRIs or other antidepressants are complicated due to potential induction of a manic episode or promote rapid cycling. Nevertheless, it is important to treat the bipolar patient with a mood stabilizer first before antidepressants are prescribed.

Conclusions

The findings of this study show that there is no convincing scientific evidence for the pharmacological treatment of comorbid PTSD in patients with bipolar disorder. Therefore, psychotherapy is preferable. When psychotherapy is not effective, pharmacotherapy can be considered. However, randomized controlled trials are needed to obtain scientific evidence for pharmacological treatment options.

Disclosure

No significant relationships.
Covid-19 pandemic and suicidal risk among adolescents
Authors: Gonçalves Cerejeira J. , Vallecillo Adame C. , Uribe S. , Santos Carrasco I. , Jiménez Aparicio T. , De Andrés Lobo C. , Queipo De Llano De La Viuda M. , Gonzaga Ramírez A. , Guerra Valera G.
Published: September 2022

Introduction

The Covid-19 pandemic has had a significant impact on the mental health of adolescents. Several descriptive studies and systematic reviews have shown an increase in suicide rates in this age group.

Objectives

- To present a literary review on the impact of the Covid-19 pandemic on the mental health and suicidal behavior of adolescents around the world. - To present data on admission rates due to suicidal behavior during the first year of the Covid-19 pandemic in a Spanish child-adolescent psychiatric hospitalization unit.

Methods

- We will present a literature review and a retrospective cross-sectional study on admission rates for suicidal behavior in a child-adolescent psychiatric hospitalization unit. - Admission rates for suicidal behavior during the year prior to the pandemic will be compared with rates relative to the first year of the pandemic.

Results

- We have found a significant increase in admission rates for suicidal behavior during the year of the pandemic. Similar results have been found in different studies and meta-analyzes. - The socio-demographic characteristics of the patients are quite similar in the two periods of time analyzed, but the reference to intra-family problems has been more frequent in the year of the pandemic.

Conclusions

Our data is in line with other studies suggesting that the Covid-19 pandemic has had a strong impact on teenage suicidal behavior.

Disclosure

No significant relationships.
Psychoeducation of Parents of Children with Autism Spectrum Disorders
Authors: Ivanov M. , Bogacheva O. , Simashkova N.
Published: September 2022

Introduction

The family of a child with a mental illness is a significant source for his support in harmonizing his development and achieving successful socialization.

Objectives

The objective of the survey is to develop a psychoeducational program for parents.

Methods

Questionnaire “Parental attitude to children’s illnesses” (V.E. Kagan, I.P. Zhuravleva) Parents of 39 (22 mothers and 17 fathers) children aged from 3 to 6 with ASD - autism spectrum disorders (F84.01; F84.02; F84.11).

Results

Parents of children with ASD often do not realize the morbid nature of changes in the children`s behavior and interpret them as spontaneity, pamperedness or even giftedness. Most parents underestimated the doctor’s recommendations for compliance with the treatment regime. Taking into account the parents` complaints and the difficulties of understanding the child`s problems, a psychoeducational course was developed, including 7 sessions: 1. acquaintance; 2. the concept of ASD, etiological factors, features of manifestation; 3. the role of the family in the treatment and rehabilitation process; 4. development of mental functions in children with ASD; 5. emotional development of children with ASD; formation of communication skills and social adaptation; 6. training organization and correctional and developmental classes for children with ASD; 7. summing up. The psychoeducational course is carried out in the form of group thematic seminars 7 meetings once a week for 1.5-2 hours. After completing the course, some families remain on individual psychological follow-up.

Conclusions

Completing a psychoeducational course makes it possible to fill the lack of information regarding the disease and treatment tactics, increases compliance and harmonizes parent-child relationships.

Disclosure

No significant relationships.
Dual Diagnosis, Double Trouble
Authors: Lopes J. , Freitas R.
Published: September 2022

Introduction

Many individuals with severe mental illness (SMI) have substance use disorder comorbidity. Dual diagnosis makes the approach and management of these patients even more challenging since the lack of improvement in either pathologies can lead to a deterioration of both.

Objectives

To illustrate, through the presentation of two cases, the clinical challenges in managing a patient with dual diagnosis

Methods

Clinical case presentation through retrospective review of clinical notes and non-systematic literature review on this topic

Results

We present the clinical cases of two women diagnosed with Bipolar Disorder and (poly)Substance Use Disorder since adolescence, who have a history of multiple hospitalizations due to mostly maniform symptoms. The complexity of case management is evident, both at the pharmacological level and in psychosocial intervention. This is aggravated by the difficulty in maintaining adherence to the therapeutic project and frequent relapses.

Conclusions

Current evidence points to the beneficial effect of a combined pharmacological and psychosocial approach, which must be comprehensive, individualized and require differentiation at various levels that are difficult to achieve and make the treatment of these situations an even greater challenge.

Using illustrative examples, this review draws attention to the practical difficulties in managing situations where substance use is associated with SMI.

Disclosure

No significant relationships.
Clarifying Definitions of „Race“, Racism, and Ethnocentrism
Authors: Küey L.
Published: September 2022

Human beings need social group identities. These may be based on age, sex, gender and gender identity, ethnicity, religious beliefs, language, nationality and etc. In fact, in-group identities, collaborations and reference systems have positive effects on health / mental health. But, the problematic issue is the process of Othering and Dehumanization of the group designated to be the Other. Othering, rising from imagined or the expectation of generalized differences and used to distinguish groups of people as separate from the norm reinforces and maintains discrimination. Social power relations determine the stratification of ‘them’ and ‘us’. Whether a group is to be designated as the Other and labelled with prejudice will depend on the zeitgeist of the current dominant social power. Dehumanization created many tragedies via genocide, slavery, racism, sexism, and other intolerant forms of violence. Theories, generally termed as scientific racism of late 19th. & early 20th. centuries, times of colonialism, assumed that some races are inferior to others, and that differential treatment of races is consequently justified. Such approaches led to movements of unification / purification practices which cannot be legitimate and caused vast individual and institutional racial discrimination, human rights violations and violence. As a social determinant of health, racial discrimination and ethnocentrism, a powerful force that weakens human relations, continue to afflict the health and mental health conditions of people. Albeit racial discrimination, peoples of the world also have a history of effective praxis of inclusive ways of solving conflicts of interests between in-groups and out-groups.

Disclosure

No significant relationships.
Couvade Syndrome: Origin, Characterization, and Frequency
Authors: Sá Couto J. , Pão Trigo M. , Da Luz B. , Rodrigues J. , Ventura Gil T.
Published: September 2022

Introduction

The word couvade originated from the French verb couver, meaning to hatch, nest, or brood. Custom of Couvade or Couvade Syndrome (CS) is a poorly understood phenomenon observed since ancient times, in which the expectant father experiences somatic and psychological symptoms of pregnancy.

Objectives

Defining what is CS. Identifying possible origin. Hypothesizing causes. Identifying CS frequency.

Methods

PubMed
database search, with “Couvade syndrome” keyword expression. Seven articles were selected among the best matches. Reference lists of articles were reviewed to identify additional articles.

Results

Currently, there are several views on this phenomenon, including religious, cultural, medical, psychoanalytic, and psychological. CS is used in Psychiatry to describe somatic symptoms resembling pregnancy and/or childbirth in expecting fathers, such as weight gain, diarrhea or constipation, toothache, and headache. Lipkin and Lamb (1982) studied 300 couples from New York: they diagnosed Couvade Syndrome in 22,5% of fathers. Nevertheless, Brennan et al. (2007) found different incidence rates of CS diagnose in different areas of the world: 20% in Sweden; 25–97% in United States; 61% in Thailand; 68% in China; 35% in Russia.

Conclusions

Whether CS constitutes a disease entity, or it should be considered a ritual or custom remains a matter of debate. Different rates of CS around the globe may indicate that culture plays an important role. It may be a way for fathers-to-be to cope with changes imposed by pregnancy in the mother and in the couple. Overall, it is a fascinating intersection between the physiological and psychological realms.

Disclosure

No significant relationships.