bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of a low-intensity static magnetic field in accelerating upper canine retraction: a randomized controlled clinical trial
Authors: Alqaisi Nataly N. , Haddad Rania A. , Amasha Hani M.
Published: April 2024

Introduction

Neodymium-iron-boron magnets have been suggested as a contemporary method for accelerating the process of orthodontic tooth movement (OTM).

A limited number of clinical trials evaluated their effectiveness in accelerating OTM which is desirable for both orthodontists and patients.

The present study aimed to investigate the effectiveness of a low-intensity static magnetic field (SMF) in accelerating upper canine retraction movement.

Materials and methods

Seventeen patients (mean age 20.76 ± 2.9 years) with their orthodontic treatment decision to extract the upper and lower first premolars due to bimaxillary protrusion malocclusion were included in this split-mouth study. Canine retraction was performed using Nickel-titanium (Ni-Ti) closed-coil springs (150 g of force on each side). The experimental side received SMF via an auxiliary wire that carried 4-neodymium iron-born magnets with an air gap of 2 mm between the magnets to produce a magnetic field density of 414 mT in the region corresponding to the lateral ligament of the upper canine. To determine the rate of upper canine retraction and upper molar drift, alginate impressions were taken once a month to create plaster casts, which were analyzed digitally via a three-dimensional method.

Results

The rate of upper canine retraction was significantly greater (P < 0.05) on the SMF side than that on the control side during the first and second months, with an overall duration (19.16%) that was greater than that on the control side. The peak acceleration occurred during the second month (38.09%).

No significant differences in upper molar drift were detected between the experimental and control sides (P > 0.05).

Conclusion

A low-intensity static magnetic field was effective at accelerating upper canine retraction. The difference between the two sides was statistically significant but may not be clinically significant.

The SMF did not affect upper molar drift during the upper canine retraction phase.

Trial registration

The trial was retrospectively registered at the ISRCTN registry (ISRCTN59092624) (31/05/2022).
Association of child abuse and neglect training with filing reports of concern to child welfare services: a cross-sectional study
Authors: Birungi Nancy , Berge Karin Goplerud , Åstrøm Anne Nordrehaug , Brattabø Ingfrid Vaksdal
Published: April 2024

Background

The aptitude, knowledge, and competence of dental health personnel on child abuse and neglect (CAN) is not optimal for deciding when to file a report of concern to child welfare services (CWS).

Objectives

The aim of this study was, firstly, to assess the association of the public dental health personnel ‘s (PDHP) training on CAN received in the last three work years, i.e., in 2016 through 2018 with filing reports to the CWS in the same period and secondly to assess the association of expressed need of training on CAN with filing reports to the CWS.

Methods

This cross-sectional study uses data from an electronic survey census of PDHP from Norway (n = 1791) conducted in 2019. The Pearson chi-square test, non-parametric tests, logistic, and negative binomial regression were used for unadjusted and adjusted analysis. Data was reported with proportions, odds ratios (OR), incidence rate ratios and 95% confidence intervals (CIs).

Results

From 2016 to 2018, the prevalence estimate of filing reports to CWS was 50%, with a mean (standard deviation) of 1.39 (2.11) reports sent. The logistic regression analysis showed an association between filing reports of concern and CAN training in the last three years. Compared to those that had not received CAN training during the three previous years, the ORs (95% CI) for filing reports to the CWS during the same period was 2.5 (1.6-4.0) for one day CAN work training, 3.2 (2.0-5.1) for 2–4 days CAN training and 4.9 (2.6–9.4) for five or more days CAN training. Compared to workers who did not need training in reporting (routines of CAN), those who expressed the need for a little more and more training were less likely to file a report. The corresponding OR were 0.6 (0.4–0.9) and 0.6 (0.3–0.9), respectively.

Conclusion

CAN training during the last three years is associated with filing reports of concern to CWS in the same period among PDHP in Norway. The likelihood of filing CAN reports increased with the number of days of CAN training received. Secondly, the PDHP with an expressed need for training on CAN routines were less likely to report suspicions to CWS.
Functional testing is a complementary tool for the diagnosis of vaginitis
Authors: Feng Danqin , Zhang Fuhui , Cai Jianguo , Zhang Yansheng , Yan Honghong , Yang Yichi , Zhong Hongxiu , Ye Huiming
Published: April 2024

Objective

Vaginal microbiota evaluation is a methodology widely used in China to diagnose various vaginal inflammatory diseases. Although vaginal microbiota evaluation has many advantages, it is time-consuming and requires highly skilled and experienced operators. Here, we investigated a six-index functional test that analyzed pH, hydrogen peroxide (H2O2), leukocyte esterase (LEU), sialidase (SNA), β-glucuronidase (GUS), and acetylglucossidase (NAG), and determined its diagnostic value by comparing it with morphological tests of vaginal microbiota.

Materials and methods

The research was conducted using data extracted from the Laboratory Information System of Women and Children’s Hospital. A total of 4902 subjects, ranging in age from 35.4 ± 9.7 years, were analyzed. During the consultation, a minimum of two vaginal swab specimens per patient were collected for both functional and morphological testing. Fisher’s exact was used to analyze data using SPSS.

Results

Of the 4,902 patients, 2,454 were considered to have normal Lactobacillus morphotypes and 3,334 were considered to have normal dominant microbiota. The sensitivity and specificity of H2O2-indicating Lactobacillus morphotypes were 91.3% and 25.28%, respectively, while those of pH-indicating Lactobacillus morphotypes were 88.09% and 59.52%, respectively. The sensitivity and specificity of H2O2-indicating dominant microbiota were 91.3% and 25.3%, respectively, while those of pH-indicating dominant microbiota were 86.27% and 64.45%, respectively. The sensitivity and specificity of NAG for vulvovaginal candidiasis were 40.64% and 84.8%, respectively. For aerobic vaginitis, GUS sensitivity was low at 0.52%, while its specificity was high at 99.93%; the LEU sensitivity and specificity values were 94.73% and 27.49%, respectively. Finally, SNA sensitivity and specificity for bacterial vaginosis were 80.72% and 96.78%, respectively.

Conclusion

Functional tests (pH, SNA, H2O2, LEU) showed satisfactory sensitivity for the detection of vaginal inflammatory diseases. However, these tests lacked specificity, making it difficult to accurately identify specific pathologies. By contrast, NAG and GUS showed excellent specificity in identifying vaginal inflammatory diseases, but their sensitivity was limited. Therefore, functional tests alone are not sufficient to diagnose various vaginal inflammatory diseases. When functional and morphological tests are inconsistent, morphological tests are currently considered the preferred reference method.
Association between oxidative balance score and rheumatoid arthritis in female: a cross-sectional study
Authors: La Rui , Zhou Liyu , Yin Yunfei , Lu Lingchen , Li Lisong , Jiang Dinghua , Huang Lixin , Wu Qian
Published: April 2024

Objective

Although oxidative stress is a recognized factor of inflammation, the correlation between oxidative balance score (OBS), a biomarker indicating the balance of oxidation and antioxidant, and rheumatoid arthritis (RA), an immune system disease that tends to occur in women, remains unexplored. Hence, the aim of this study was to investigate the potential association between OBS and RA in women.

Methods

Observational surveys were performed by employing information extracted from the National Health and Nutrition Examination Survey (NHANES) for the period 2007–2018. Various statistical techniques were employed to investigate the association between OBS and RA, encompassing multivariable logistic regression analysis, subgroup analyses, smooth curve fitting, and threshold effect analysis.

Results

The study included 8219 female participants, including 597 patients with RA. The results showed that higher Total OBS (TOBS) significantly correlated with lower RA prevalence in the entirely modified model [odd ratio (OR) = 0.968; 95% confidence interval (CI) = 0.952 to 0.984; P = 0.0001]. Dietary OBS (DOBS) and lifestyle OBS (LOBS) also negatively correlated with RA. This association was remarkably consistent across TOBS subgroups by age, race, education level, family poverty-to-income ratio (PIR), hypertension and diabetes. Smooth curve fitting and threshold effect analysis also revealed the linear relationship between OBS and RA.

Conclusions

Overall, OBS was negatively associated with RA in female. This study suggested that an antioxidant diet and lifestyle may be promising measures to prevent RA in female.
Comparative effectiveness of Propolis with chlorhexidine mouthwash on gingivitis – a randomized controlled clinical study
Authors: Gunjal Shilpa , Pateel Deepak Gowda Sadashivappa
Published: April 2024

Background

To assess and compare the effectiveness of propolis mouthwash with chlorhexidine mouthwash in the reduction of plaque and gingivitis.

Methods

A single centre, latin-square cross-over, double masked, randomized controlled clinical trial was conducted on 45 chronic generalized gingivitis subjects who were chosen from the dental clinic of MAHSA University, Malaysia. A total of 45 subjects were randomly assigned into one of the three different groups (n = 15 each) using a computer-generated random allocation sequence: Group A Propolis mouthwash; Group B Chlorhexidine mouthwash; and Group C Placebo mouthwash. Supragingival plaque and gingival inflammation were assessed by full mouth Plaque index (PI) and gingival index (GI) at baseline and after 21 days. The study was divided into three phases, each phase lasted for 21 days separated by a washout period of 15 days in between them. Groups A, B and C were treated with 0.2% Propolis, Chlorhexidine, and Placebo mouthwash, respectively, in phase I. The study subjects were instructed to use the assigned mouthwash twice daily for 1 min for 21 days. On day 22nd, the subjects were recalled for measurement of PI and GI. After phase I, mouthwash was crossed over as dictated by the Latin square design in phase II and III.

Results

At baseline, intergroup comparison revealed no statistically significant difference between Groups A, B and C (p > 0.05). On day 21, one-way ANOVA revealed statistically significant difference between the three groups for PI (p < 0.001) and GI (p < 0.001). Bonferroni post-hoc test showed statistically significant difference between Propolis and Chlorhexidine mouthwash (P < 0.001), with higher reduction in the mean plaque and gingival scores in propolis group compared to chlorhexidine and placebo groups.

Conclusions

Propolis mouthwash demonstrated significant improvement in gingival health and plaque reduction. Thus, it could be used as an effective herbal mouthwash alternative to chlorhexidine mouthwash.

Trial registration

The trial was retrospectively registered on 25/07/2019 at clinicaltrials.gov and its identifier is NCT04032548.
PD-1/PD-L1 axis induced host immunosuppression via PI3K/Akt/mTOR signalling pathway in piglets infected by Glaesserella Parasuis
Authors: Li Jingyang , Liu Siyu , Dong Qiaoli , Fu Yunjian , Sun Yamin , Luo Ronghui , Tian Xinyue , Guo Ling , Liu Wei , Qiu Yinsheng , Lu Qirong , Ye Chun , Zong Bingbing , Fu Shulin
Published: April 2024

Glaesserella parasuis, an important respiratory bacterial pathogen, causes Glässer’s disease in piglets, with potential immunosuppression. We established a piglet infection model and explored the immunosuppression mechanism to improve our understanding of the host immune response to G. parasuis. Twenty piglets were randomly divided into two groups (n = 10). The infection group was intraperitoneally challenged with 2 × 108 CFU of G. parasuis in 2 mL TSB. The control group was intraperitoneally injected with equivalent TSB. After 72 h, the piglets were sacrificed, and spleen tissue was collected. PD-1/PD-L1 expression was determined. The splenocytes were isolated to detect CD3+ T, CD3+CD4+ T, CD3+CD8+ T and CD3−CD21+cell differentiation. Via data-independent acquisition (DIA), we compared the proteomics of healthy and infected spleen tissues. Glaesserella parasuis modified CD3+ T, CD3+CD4+ T, CD3+CD8+ T and CD3−CD21+ cell differentiation and PD-1/PD-L1 expression in the spleen. The infection group had 596 proteins with significant differences in expression, of which 301 were significantly upregulated and 295 downregulated. Differentially expressed proteins (DEPs) were mainly related to immune responses. This is the first study on PD-1/PD-L1 expression in the spleen associated with immunosuppression in a piglet model to explore the protein changes related to immune responses via DIA.
Strategies to enhance the ability of nerve guidance conduits to promote directional nerve growth
Authors: Zhang Ziyue , Ma Muyuan
Published: April 2024

Severely damaged peripheral nerves will regenerate incompletely due to lack of directionality in their regeneration, leading to loss of nerve function. To address this problem, various nerve guidance conduits (NGCs) have been developed to provide guidance for nerve repair. However, their clinical application is still limited, mainly because its effect in promoting nerve repair is not as good as autologous nerve transplantation. Therefore, it is necessary to enhance the ability of NGCs to promote directional nerve growth. Strategies include preparing various directional structures on NGCs to provide contact guidance, and loading various substances on them to provide electrical stimulation or neurotrophic factor concentration gradient to provide directional physical or biological signals.
Tertiary lymphoid structural heterogeneity determines tumour immunity and prospects for clinical application
Authors: Zhang Yuyuan , Xu Mengjun , Ren Yuqing , Ba Yuhao , Liu Shutong , Zuo Anning , Xu Hui , Weng Siyuan , Han Xinwei , Liu Zaoqu
Published: April 2024

Tertiary lymphoid structures (TLS) are clusters of immune cells that resemble and function similarly to secondary lymphoid organs (SLOs). While TLS is generally associated with an anti-tumour immune response in most cancer types, it has also been observed to act as a pro-tumour immune response. The heterogeneity of TLS function is largely determined by the composition of tumour-infiltrating lymphocytes (TILs) and the balance of cell subsets within the tumour-associated TLS (TA-TLS). TA-TLS of varying maturity, density, and location may have opposing effects on tumour immunity. Higher maturity and/or higher density TLS are often associated with favorable clinical outcomes and immunotherapeutic response, mainly due to crosstalk between different proportions of immune cell subpopulations in TA-TLS. Therefore, TLS can be used as a marker to predict the efficacy of immunotherapy in immune checkpoint blockade (ICB). Developing efficient imaging and induction methods to study TA-TLS is crucial for enhancing anti-tumour immunity. The integration of imaging techniques with biological materials, including nanoprobes and hydrogels, alongside artificial intelligence (AI), enables non-invasive in vivo visualization of TLS. In this review, we explore the dynamic interactions among T and B cell subpopulations of varying phenotypes that contribute to the structural and functional diversity of TLS, examining both existing and emerging techniques for TLS imaging and induction, focusing on cancer immunotherapies and biomaterials. We also highlight novel therapeutic approaches of TLS that are being explored with the aim of increasing ICB treatment efficacy and predicting prognosis.
Loss of lncRNA LINC01056 leads to sorafenib resistance in HCC
Authors: Chan Yau-Tuen , Wu Junyu , Lu Yuanjun , Li Qiucheng , Feng Zixin , Xu Lin , Yuan Hongchao , Xing Tingyuan , Zhang Cheng , Tan Hor-Yue , Feng Yibin , Wang Ning
Published: April 2024

Background and aims

Sorafenib is a major nonsurgical option for patients with advanced hepatocellular carcinoma (HCC); however, its clinical efficacy is largely undermined by the acquisition of resistance. The aim of this study was to identify the key lncRNA involved in the regulation of the sorafenib response in HCC.

Materials and methods

A clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) single-guide RNA (sgRNA) synergistic activation mediator (SAM)-pooled lncRNA library was applied to screen for the key lncRNA regulated by sorafenib treatment. The role of the identified lncRNA in mediating the sorafenib response in HCC was examined in vitro and in vivo. The underlying mechanism was delineated by proteomic analysis. The clinical significance of the expression of the identified lncRNA was evaluated by multiplex immunostaining on a human HCC microtissue array.

Results

CRISPR/Cas9 lncRNA library screening revealed that Linc01056 was among the most downregulated lncRNAs in sorafenib-resistant HCC cells. Knockdown of Linc01056 reduced the sensitivity of HCC cells to sorafenib, suppressing apoptosis in vitro and promoting tumour growth in mice in vivo. Proteomic analysis revealed that Linc01056 knockdown in sorafenib-treated HCC cells induced genes related to fatty acid oxidation (FAO) while repressing glycolysis-associated genes, leading to a metabolic switch favouring higher intracellular energy production. FAO inhibition in HCC cells with Linc01056 knockdown significantly restored sensitivity to sorafenib. Mechanistically, we determined that PPARα is the critical molecule governing the metabolic switch upon Linc01056 knockdown in HCC cells and indeed, PPARα inhibition restored the sorafenib response in HCC cells in vitro and HCC tumours in vivo. Clinically, Linc01056 expression predicted optimal overall and progression-free survival outcomes in HCC patients and predicted a better sorafenib response. Linc01056 expression indicated a low FAO level in HCC.

Conclusion

Our study identified Linc01056 as a critical epigenetic regulator and potential therapeutic target in the regulation of the sorafenib response in HCC.
Predictors of maternal health services uptake in West African region: a multilevel multinomial regression analysis of demographic health survey reports
Authors: Habte Aklilu , Hailegebreal Samuel , Simegn Atsedu Endale
Published: April 2024

Background

Pursuant to studies, receiving the three key maternal health services (Antenatal Care, Skilled Delivery Service, and Postnatal Care) in a continuum could prevent 71% of global maternal deaths. Despite the Western African region being known for its high maternal death and poor access to maternal health services, there is a dearth of studies that delve into the spectrum of maternal health services uptake. Hence, this study aimed to assess the level and predictors of partial and adequate utilization of health services in a single analytical model using the most recent Demographic and Health Survey (DHS) data (2013–2021).

Methods

This study was based on the appended women's (IR) file of twelve West African countries. STATA software version 16 was used to analyze a weighted sample of 89,504 women aged 15–49 years. A composite index of maternal health service utilization has been created by combining three key health services and categorizing them into ‘no’, ‘partial’, or ‘adequate’ use. A multilevel multivariable multinomial logistic regression analysis was carried out to examine the effects of each predictor on the level of service utilization. The degree of association was reported using the adjusted relative risk ratio (aRRR) with a corresponding 95% confidence interval, and statistical significance was declared at p < 0.05.

Results

66.4% (95% CI: 64.9, 67.7) and 23.8% (95% CI: 23.3, 24.2) of women used maternal health services partially and adequately, respectively. Togo has the highest proportion of women getting adequate health care in the region, at 56.7%, while Nigeria has the lowest proportion, at 11%. Maternal education, residence, wealth index, parity, media exposure (to radio and television), enrolment in health insurance schemes, attitude towards wife beating, and autonomy in decision-making were identified as significant predictors of partial and adequate maternal health service uptake.

Conclusion

The uptake of adequate maternal health services in the region was found to be low. Stakeholders should plan for and implement interventions that increase women's autonomy. Program planners and healthcare providers should give due emphasis to those women with no formal education and from low-income families. The government and the private sectors need to collaborate to improve media access and increase public enrolment in health insurance schemes.
Impact of postpartum weight change on metabolic syndrome and its components among women with recent gestational diabetes mellitus
Authors: Phaloprakarn Chadakarn , Suthasmalee Sasiwan , Tangjitgamol Siriwan
Published: April 2024

Background

While postpartum weight changes may affect the levels of metabolic parameters, the direct effects of weight changes in the postpartum period on changes in the prevalence rates of metabolic syndrome and its components remain unstudied. This study aimed to investigate the effects of postpartum weight changes between 6 weeks and 6 months on changes in the prevalence rates of metabolic syndrome and its components in women who have recently experienced gestational diabetes mellitus.

Methods

This prospective cohort study included 171 postpartum women with recent gestational diabetes mellitus, who underwent serial weight and metabolic risk factor assessments at 6 weeks and 6 months postpartum. Weight changes between these time points were classified as weight loss (> 2 kg), weight stability (± 2 kg), or weight gain (> 2 kg). Metabolic syndrome comprised the following metabolic risk factors: large waist circumference, elevated blood pressure, elevated fasting plasma glucose levels, high triglyceride levels, and low high-density lipoprotein cholesterol levels.

Results

Of the 171 women in our cohort, 30 women (17.5%) lost > 2 kg of body weight, while 85 (49.7%) maintained a stable weight and 56 (32.8%) gained > 2 kg. The weight loss group experienced significant changes in the prevalence rates of the following metabolic risk factors compared to the weight stability and weight gain groups: large waist circumference (% change: − 26.7 vs − 5.9 vs 5.4, respectively; p = 0.004), elevated fasting plasma glucose levels (% change: − 3.4 vs 18.9 vs 26.8, respectively; p = 0.022), and high triglyceride levels (% change: − 30.0 vs 0 vs − 7.2, respectively; p = 0.024). A significantly greater decrease in the prevalence of metabolic syndrome was also found in the weight loss group than in the other two groups (% change: − 20.0 vs 11.8 vs 14.2, respectively; p = 0.002).

Conclusions

Weight changes from 6 weeks to 6 months postpartum significantly altered the prevalence rates of metabolic syndrome and its components in women with recent gestational diabetes mellitus. Early postpartum weight loss can reverse metabolic risk factors and reduce the prevalence of metabolic syndrome.

Trial registration

Thai Clinical Trials Registry: Registration no. TCTR20200903001. Date of registration: September 3, 2020. Date of initial participant enrolment: September 7, 2020.
Medial patellar ligament reconstruction in combination with derotational distal femoral osteotomy for treating recurrent patellar dislocation in the presence of increased femoral anteversion: a systematic review
Authors: Yang Jinghong , Zhong Jun , Li Han , Du Yimin , Liu Xu , Li Zhong , Liu Yanshi
Published: April 2024

Background

Medial patellar ligament reconstruction (MPFL-R) in combination with derotational distal femoral osteotomy (DDFO) for treating recurrent patellar dislocation (RPD) in the presence of increased femoral anteversion is one of the most commonly used surgical techniques in the current clinical practice. However, there are limited studies on the clinical outcomes of MPFL-R in combination with DDFO to treat RPD in the presence of increased femoral anteversion.

Purpose

To study the role of MPFL-R in combination with DDFO in the treatment of RPD in the presence of increased femoral anteversion.

Methods

A systematic review was performed according to the PRISMA guidelines by searching the Medline, Embase, Web of Science, and Cochrane Library databases through June 1, 2023. Studies of patients who received MPFL-R in combination with DDFO after presenting with RPD and increased femoral anteversion were included. Methodological quality was assessed using the MINORS (Methodological Index for Nonrandomized Studies) score. Each study’s basic characteristics, including characteristic information, radiological parameters, surgical techniques, patient-reported outcomes, and complications, were recorded and analyzed.

Results

A total of 6 studies with 231 patients (236 knees) were included. Sample sizes ranged from 12 to 162 patients, and the majority of the patients were female (range, 67-100%). The mean age and follow-up ranges were 18 to 24 years and 16 to 49 months, respectively. The mean femoral anteversion decreased significantly from 34° preoperatively to 12° postoperatively. In studies reporting preoperative and postoperative outcomes, significant improvements were found in the Lysholm score, Kujala score, International Knee Documentation Committee score, and visual analog scale for pain. Postoperative complications were reported in all studies, with an overall reported complication rate of 4.7%, but no redislocations occurred during the follow-up period.

Conclusion

For RPD with increased femoral anteversion, MPFL-R in combination with DDFO leads to a good clinical outcome and a low redislocation rate. However, there was no consensus among researchers on the indications for MPFL-R combined with DDFO in the treatment of RPD.
Identification and characterization of a new pathologic mutation in a large Leber hereditary optic neuropathy pedigree
Authors: Emperador Sonia , Habbane Mouna , López-Gallardo Ester , del Rio Alejandro , Llobet Laura , Mateo Javier , Sanz-López Ana María , Fernández-García María José , Sánchez-Tocino Hortensia , Benbunan-Ferreiro Sol , Calabuig-Goena María , Narvaez-Palazón Carlos , Fernández-Vega Beatriz , González-Iglesias Hector , Urreizti Roser , Artuch Rafael , Pacheu-Grau David , Bayona-Bafaluy Pilar , Montoya Julio , Ruiz-Pesini Eduardo
Published: April 2024

Background

Most patients suffering from Leber hereditary optic neuropathy carry one of the three classic pathologic mutations, but not all individuals with these genetic alterations develop the disease. There are different risk factors that modify the penetrance of these mutations. The remaining patients carry one of a set of very rare genetic variants and, it appears that, some of the risk factors that modify the penetrance of the classical pathologic mutations may also affect the phenotype of these other rare mutations.

Results

We describe a large family including 95 maternally related individuals, showing 30 patients with Leber hereditary optic neuropathy. The mutation responsible for the phenotype is a novel transition, m.3734A > G, in the mitochondrial gene encoding the ND1 subunit of respiratory complex I. Molecular-genetic, biochemical and cellular studies corroborate the pathogenicity of this genetic change.

Conclusions

With the study of this family, we confirm that, also for this very rare mutation, sex and age are important factors modifying penetrance. Moreover, this pedigree offers an excellent opportunity to search for other genetic or environmental factors that additionally contribute to modify penetrance.
Delayed discharge in inpatient psychiatric care: a systematic review
Authors: Teale Ashley-Louise , Morgan Ceri , Jenkins Tom A. , Jacobsen Pamela
Published: April 2024

Background

Delayed discharge is problematic. It is financially costly and can create barriers to delivering best patient care, by preventing return to usual functioning and delaying admissions of others in need. This systematic review aimed to collate existing evidence on delayed discharge in psychiatric inpatient settings and to develop understanding of factors and outcomes of delays in these services.

Methods

A search of relevant literature published between 2002 and 2022 was conducted on Pubmed, PsycInfo and Embase. Studies of any design, which published data on delayed discharge from psychiatric inpatient care in high income countries were included. Studies examining child and adolescent, general medical or forensic settings were excluded. A narrative synthesis method was utilised. Quality of research was appraised using the Mixed Methods Appraisal Tool (MMAT).

Results

Eighteen studies from England, Canada, Australia, Ireland, and Norway met the inclusion criteria. Six main reasons for delayed discharge were identified: (1) accommodation needs, (2) challenges securing community or rehabilitation support, (3) funding difficulties, (4) family/carer factors, (5) forensic considerations and (6) person being out of area. Some demographic and clinical factors were also found to relate to delays, such as having a diagnosis of schizophrenia or other psychotic disorder, cognitive impairment, and increased service input prior to admission. Being unemployed and socially isolated were also linked to delays. Only one study commented on consequences of delays for patients, finding they experienced feelings of lack of choice and control. Four studies examined consequences on services, identifying high financial costs.

Conclusion

Overall, the findings suggest there are multiple interlinked factors relevant in delayed discharge that should be considered in practice and policy. Suggestions for future research are discussed, including investigating delayed discharge in other high-income countries, examining delayed discharge from child and forensic psychiatric settings, and exploring consequences of delays on patients and staff. We suggest that future research be consistent in terms used to define delayed discharge, to enhance the clarity of the evidence base.

Review registration number on PROSPERO

292515.

Date of registration

9th December 2021.
Effects of robotic-assisted early mobilization versus conventional mobilization in intensive care unit patients: prospective interventional cohort study with retrospective control group analysis
Authors: Huebner Lucas , Warmbein Angelika , Scharf Christina , Schroeder Ines , Manz Kirsi , Rathgeber Ivanka , Gutmann Marcus , Biebl Johanna , Mehler-Klamt Amrei , Huber Jana , Eberl Inge , Kraft Eduard , Fischer Uli , Zoller Michael
Published: April 2024

Background

Approximately one in three survivors of critical illness suffers from intensive-care-unit-acquired weakness, which increases mortality and impairs quality of life. By counteracting immobilization, a known risk factor, active mobilization may mitigate its negative effects on patients. In this single-center trial, the effect of robotic-assisted early mobilization in the intensive care unit (ICU) on patients’ outcomes was investigated.

Methods

We enrolled 16 adults scheduled for lung transplantation to receive 20 min of robotic-assisted mobilization and verticalization twice daily during their first week in the ICU (intervention group: IG). A control group (CG) of 13 conventionally mobilized patients after lung transplantation was recruited retrospectively. Outcome measures included the duration of mechanical ventilation, length of ICU stay, muscle parameters evaluated by ultrasound, and quality of life after three months.

Results

During the first week in the ICU, the intervention group received a median of 6 (interquartile range 3–8) robotic-assisted sessions of early mobilization and verticalization. There were no statistically significant differences in the duration of mechanical ventilation (IG: median 126 vs. CG: 78 h), length of ICU stay, muscle parameters evaluated by ultrasound, and quality of life after three months between the IG and CG.

Conclusion

In this study, robotic-assisted mobilization was successfully implemented in the ICU setting. No significant differences in patients’ outcomes were observed between conventional and robotic-assisted mobilization. However, randomized and larger studies are necessary to validate the adequacy of robotic mobilization in other cohorts.

Trial registration: This single-center interventional trial was registered in clinicaltrials.gov as NCT05071248 on 27/08/2021.
Pharmacological inhibition of mTORC1 reduces neural death and damage volume after MCAO by modulating microglial reactivity
Authors: Villa-González Mario , Rubio Marina , Martín-López Gerardo , Mallavibarrena Paula R. , Vallés-Saiz Laura , Vivien Denis , Wandosell Francisco , Pérez-Álvarez Maria José
Published: April 2024

Ischemic stroke is a sudden and acute disease characterized by neuronal death, increment of reactive gliosis (reactive microglia and astrocytes), and a severe inflammatory process. Neuroinflammation is an early event after cerebral ischemia, with microglia playing a leading role. Reactive microglia involve functional and morphological changes that drive a wide variety of phenotypes. In this context, deciphering the molecular mechanisms underlying such reactive microglial is essential to devise strategies to protect neurons and maintain certain brain functions affected by early neuroinflammation after ischemia. Here, we studied the role of mammalian target of rapamycin (mTOR) activity in the microglial response using a murine model of cerebral ischemia in the acute phase. We also determined the therapeutic relevance of the pharmacological administration of rapamycin, a mTOR inhibitor, before and after ischemic injury. Our data show that rapamycin, administered before or after brain ischemia induction, reduced the volume of brain damage and neuronal loss by attenuating the microglial response. Therefore, our findings indicate that the pharmacological inhibition of mTORC1 in the acute phase of ischemia may provide an alternative strategy to reduce neuronal damage through attenuation of the associated neuroinflammation.
A placebo-controlled, crossover trial to investigate the efficacy of tiotropium bromide or placebo added to usual care in stable symptomatic post-hematopoietic stem cell transplantation (HSCT) bronchiolitis obliterans syndrome (BOS)
Authors: Dini Naeemeh , Khoshbin Amin Pastaki , Aliannejad Rasoul , Bakhshandeh Hooman , Najafizadeh Katayoun , Mehdizadeh Mahshid , Amini Shahideh
Published: April 2024

Background

Despite the fundamental progress in hematopoietic stem cell transplant, this treatment is also associated with complications. Graft-versus-host disease is a possible complication of HSCT. Bronchiolitis obliterans syndrome (BOS) is the pulmonary form of this syndrome. Due to the high morbidity and mortality rate of BOS, various studies have been conducted in the field of drug therapy for this syndrome, although no standard treatment has yet been proposed. According to the hypotheses about the similarities between BOS and chronic obstructive pulmonary disease, the idea of using tiotropium bromide as a bronchodilator has been proposed.

Method/design

A randomized, double-blind, placebo-controlled, and crossover clinical trial is being conducted to evaluate the efficacy of tiotropium in patients with BOS. A total of 20 patients with BOS were randomly assigned (1:1) to receive a once-daily inhaled capsule of either tiotropium bromide (KP-Tiova Rotacaps 18 mcg, Cipla, India) or placebo for 1 month. Patients will receive tiotropium bromide or placebo Revolizer added to usual standard care. Measurements will include spirometry and a 6-min walking test.

Ethics/dissemination

This study was approved by the Research Ethics Committees of Imam Khomeini Hospital Complex, Tehran University of Medical Science. Recruitment started in September 2022, with 20 patients randomized. The treatment follow-up of participants with tiotropium is currently ongoing and is due to finish in April 2024. The authors will disseminate the findings in peer-reviewed publications, conferences, and seminar presentations.

Trial registration

Iranian Registry of Clinical Trial (IRCT) IRCT20200415047080N3. Registered on 2022–07-12, 1401/04/21.
Effects of transcutaneous electrical nerve stimulation on pain, function, and descending inhibition in people with non-specific chronic low-back pain: a study protocol for a randomized crossover trial
Authors: Liebano Richard E. , Sluka Kathleen A. , Roy Joshua , Savinelli Meghan , Dailey Dana L. , Riley Sean P.
Published: April 2024

Background

Low back pain (LBP) is a significant public health problem, is very prevalent, and is often characterized by the persistence of symptoms. Transcutaneous electrical nerve stimulation (TENS) may benefit people with chronic LBP because it can activate descending inhibitory pathways and inhibit central excitability. However, previous studies that have investigated the effects of TENS on pain in people with LBP have failed to use proper intensities of current, and the timing of the assessment of pain was not performed during the peak of the analgesic response or functional activities. Therefore, the present study aims to assess the effects of TENS on measures of pain, function, and descending inhibition using the maximal tolerable intensity of TENS in participants with LBP.

Methods/design

This study will be a randomized crossover trial. The participants for this study will be recruited from various places, including the University of Hartford, physical therapy clinics, and local businesses in the Hartford area, as well as online websites geared towards clinical trial recruitment. A total of 34 participants will receive all three treatments: active TENS, placebo TENS, and no treatment control. The treatment order will be randomized using a website-based randomization tool. For active TENS, a modulating frequency of 2–125 Hz will be applied with a variable pulse duration and maximal tolerable intensity for 30 min. The TENS will be left on for post-treatment testing to assess the effects during its maximally effective period for a total of 50 to 60 min. Furthermore, the intensity may be turned down if muscle twitching is present to ensure blinding of the evaluator. For placebo TENS, the unit will deliver current for 45 s, ramping to 0 in the last 15 s. The primary outcome will be pain intensity at rest and with movement, determined using the numerical pain rating scale. The secondary outcomes will be pressure pain threshold, heat pain threshold, temporal summation of pain, conditioned pain modulation, sit-to-stand test, and repeated trunk flexion. The assessments will be performed immediately before and after treatment. Statistical analysis of the data obtained will consider a significance level of p < 0.05.

Discussion

This study will provide evidence concerning the effects and mechanisms of TENS treatment in participants with chronic non-specific low back pain. The outcomes, including pain, function, and descending inhibition, will help us gain a greater understanding of how TENS can be used for these participants.

Trial registration

ClinicalTrials.gov NCT05812885. Registered on 24th May 2023.
Synthesis, anticancer evaluation, molecular docking and ADME study of novel pyrido[4ʹ,3ʹ:3,4]pyrazolo[1,5-a]pyrimidines as potential tropomyosin receptor kinase A (TrKA) inhibitors
Authors: Metwally Nadia Hanafy , Deeb Emad Abdullah , Hasani Ibrahim Walid
Published: April 2024

The starting compound 3-amino-1,7-dihydro-4H-pyrazolo[4,3-c]pyridine-4,6(5H)-dione (1) is reacted with each of diketone and β-ketoester, forming pyridopyrazolo[1,5-a]pyrimidines 4a,b and 14a,b, respectively. The compounds 4 and 14 reacted with each of aromatic aldehyde and arenediazonium salt to give the respective arylidenes and arylhydrazo derivatives, respectively. The structure of the new products was established using spectroscopic techniques. The cytotoxic activity of selected targets was tested in vitro against three cancer cell lines MCF7, HepG2 and HCT116. The data obtained from enzymatic assays of TrKA indicated that compounds 7b and 16c have the strongest inhibitory effects on TrKA with IC50 = 0.064 ± 0.0037 μg/ml and IC50 = 0.047 ± 0.0027 μg/ml, respectively, compared to the standard drug Larotrectinib with IC50 = 0.034 ± 0.0021 μg/ml for the HepG2 cancer cell line. In cell cycle analysis, compounds 7b, 15b, 16a and 16c caused the greatest arrest in cell cycle at the G2/M phase. In addition, compound 15b has a higher apoptosis-inducing effect (36.72%) than compounds 7b (34.70%), 16a (21.14) and 16c (26.54%). Compounds 7b, 16a and 16c were shown fit tightly into the active site of the TrKA kinase crystal structure (PDB: 5H3Q). Also, ADME study was performed on some selected potent anticancer compounds described in this study.
Polyvinyl chloride solvent cement poisoning: a case report
Authors: Marambahewa S. R. , Chandrasiri D. A. C. T , Wijesekara W. A. I. C. , Munasinghe B. M.
Published: April 2024

Background

S-lon® (S) is a locally produced polyvinyl chloride-based solvent cement. It is a clear, slightly viscous liquid. Other constituents include 1-cyclohexanone, 3-butanone, and 1-acetone. It is used ubiquitously for building construction in Sri Lanka. Although the clinical effects of the compound have not yet been ascertained, the constituents have been implicated in neurotoxicity, respiratory tract, eye and skin irritation, and delayed liver and renal injury.

Case description

A 42-year-old South Asian male presented following self-ingestion of S. His vital parameters were stable and initially managed symptomatically. A few hours later, he developed central nervous system depression and stridor requiring elective intubation. Examination of the upper airway revealed inflammation and edema. He was sedated and ventilated, and intravenous dexamethasone was administered. Attempts at removal of the nasogastric tube after extubation on day 3 failed. The patient had to be reintubated and sedated owing to extreme agitation not responding to routine doses of sedatives. The nasogastric tube had been amalgamated after reacting with S, forming a solid clump, later found after removal. The posterior pharynx and nasopharynx were packed and later removed before extubation. The patient made a full recovery and was transferred to the ward on day 5.

Conclusion

Ingestion of a sufficient quantity of S could result in gut absorption with central nervous system depression, coma, and even death. No antidote is available for toxicity, and management is largely supportive. As witnessed in our patient, chemical laryngitis and upper airway inflammation may lead to upper airway obstruction. Chemical reactions with medical equipment may lead to unforeseen outcomes.
In-vivo inhibition of neutral endopeptidase 1 results in higher absorbed tumor doses of [177Lu]Lu-PP-F11N in humans: the lumed phase 0b study
Authors: Rottenburger Christof , Hentschel Michael , Fürstner Markus , McDougall Lisa , Kottoros Danijela , Kaul Felix , Mansi Rosalba , Fani Melpomeni , Vija A. Hans , Schibli Roger , Geistlich Susanne , Behe Martin , Christ Emanuel R. , Wild Damian
Published: April 2024

Background

A new generation of radiolabeled minigastrin analogs delivers low radiation doses to kidneys and are considered relatively stable due to less enzymatic degradation. Nevertheless, relatively low tumor radiation doses in patients indicate limited stability in humans. We aimed at evaluating the effect of sacubitril, an inhibitor of the neutral endopeptidase 1, on the stability and absorbed doses to tumors and organs by the cholecystokinin-2 receptor agonist [177Lu]Lu-PP-F11N in patients. In this prospective phase 0 study eight consecutive patients with advanced medullary thyroid carcinoma and a current somatostatin receptor subtype 2 PET/CT scan were included. Patients received two short infusions of ~ 1 GBq [177Lu]Lu-PP-F11N in an interval of ~ 4 weeks with and without Entresto® pretreatment in an open-label, randomized cross-over order. Entresto® was given at a single oral dose, containing 48.6 mg sacubitril. Adverse events were graded and quantitative SPECT/CT and blood sampling were performed. Absorbed doses to tumors and relevant organs were calculated.

Results

Pretreatment with Entresto® showed no additional toxicity and increased the stability of [177Lu]Lu-PP-FF11N in blood significantly (p < 0.001). Median tumor-absorbed doses were 2.6-fold higher after Entresto® pretreatment (0.74 vs. 0.28 Gy/GBq, P = 0.03). At the same time, an increase of absorbed doses to stomach, kidneys and bone marrow was observed, resulting in a tumor-to-organ absorbed dose ratio not significantly different with and without Entresto®.

Conclusions

Premedication with Entresto® results in a relevant stabilization of [177Lu]Lu-PP-FF11N and consecutively increases radiation doses in tumors and organs.

Trial registration clinicaltrails.gov, NCT03647657. Registered 20 August 2018.
Tools for assessing the methodological limitations of a QES—a short note
Authors: Nøkleby Heid , Ames Heather Melanie R. , Langøien Lars Jørun , Hestevik Christine Hillestad
Published: April 2024

The increasing prevalence and application of qualitative evidence syntheses (QES) in decision-making processes underscore the need for robust tools to assess the methodological limitations of a completed QES. This commentary discusses the limitations of three existing tools and presents the authors’ efforts to address this gap. Through a simple comparative analysis, the three tools are examined in terms of their coverage of essential topic areas. The examination finds that existing assessment tools lack comprehensive coverage, clarity, and grounding in qualitative research principles. The authors advocate for the development of a new collaboratively developed evidence-based tool rooted in qualitative methodology and best practice methods. The conclusion emphasizes the necessity of a tool that can provide a comprehensive judgement on the methodological limitations of a QES, addressing the needs of end-users, and ultimately enhancing the trustworthiness of QES findings in decision-making processes.
Predicting UPDRS in Parkinson’s disease using ensembles of self-organizing map and neuro-fuzzy
Authors: Zhao Siren , Zhang Jilun , Zhang Jianbin
Published: April 2024

Parkinson's Disease (PD) is a complex, degenerative disease that affects nerve cells that are responsible for body movement. Artificial Intelligence (AI) algorithms are widely used to diagnose and track the progression of this disease, which causes symptoms of Parkinson's disease in its early stages, by predicting the results of the Unified Parkinson's Disease Rating Scale (UPDRS). In this study, we aim to develop a method based on the integration of two methods, one complementary to the other, Ensembles of Self-Organizing Map and Neuro-Fuzzy, and an unsupervised learning algorithm. The proposed method relied on the higher effect of the variables resulting from the analysis of the initial readings to obtain a correct and accurate preliminary prediction. We evaluate the developed approach on a PD dataset including speech cues. The process was evaluated with root mean square error (RMSE) and modified R square (modified R2). Our findings reveal that the proposed method is effective in predicting UPDRS outcomes by a combination of speech signals (measures of hoarseness). As the preliminary results during the evaluation showed numbers that proved the worth of the proposed method, such as UPDRS = 0.955 and RMSE approximately 0.2769 during the prediction process.