bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of synbiotics on indoxyl sulphate level, constipation, and quality of life associated with constipation in chronic haemodialysis patients: a randomized controlled trial
Authors: Lydia Aida , Indra Tities Anggraeni , Rizka Aulia , Abdullah Murdani
Published: July 2022

Background

Gut microbiota dysbiosis in patients with chronic kidney disease on haemodialysis (CKD-HD) creates an increase in proteolytic bacteria activity, leading to an increase in the production of uraemic toxins, such as indoxyl sulphate, worsening of constipation symptoms and reducing patients’ quality of life. Improving gut microbiota dysbiosis is expected to improve this condition. This study aimed to evaluate the effect of synbiotics on indoxyl sulphate levels, constipation symptoms, and constipation-related quality of life in haemodialysis patients.

Methods

This was a double-blinded randomized controlled clinical trial with a parallel design involving haemodialysis patients. We included chronic haemodialysis patients with gastrointestinal complaints, difficulty defecating, faeces with hard consistency, or a bowel movement frequency of fewer than three times per week. Patients were randomly divided into two groups (synbiotics (Lactobacillus acidophilus and Bifidobacterium longum 5x109 CFU) and placebo) for 60 days of oral intervention. All participants, caregivers, and outcome assessors were blinded to group assignment. The primary outcome was a decrease in indoxyl sulphate toxin levels. Meanwhile, improvement in constipation symptoms (measured using the Patient Assessment of Constipation: Symptoms (PAC-SYM) questionnaire) and improvement in constipation-related quality of life (measured using the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire) were assessed as secondary outcomes.

Results

We included 60 patients (30 intervention; median age of 51.23 (13.57) years, 33.3% male; 30 control; median age of 52.33 (11.29) years, 36.7% male). There was no significant difference in terms of pre- and postintervention indoxyl sulphate toxin levels in the synbiotics group compared to the placebo group (p=0.438). This study found an improvement in constipation symptoms (p = 0.006) and constipation-related quality of life (p=0.001) after synbiotic administration.

Conclusion

Two months of synbiotic supplementation did not lower indoxyl sulphate toxin levels. Nevertheless, it had a major effect in improving constipation and quality of life affected by constipation in patients undergoing chronic haemodialysis.

Trial registration

NCT04527640 (date of first registration: 26/08/2020)
A differential of the left eye and right eye neurological pupil index is associated with discharge modified Rankin scores in neurologically injured patients
Authors: Privitera Claudio M. , Neerukonda Sanjay V. , Aiyagari Venkatesh , Yokobori Shoji , Puccio Ava M. , Schneider Nathan J. , Stutzman Sonja E. , Olson DaiWai M. ,   the END PANIC Investigators, Hill Michelle , DeWitt Jessica , Atem Folefac , Barnes Arianna , Xie Donglu , Kuramatsu Joji , Koehn Julia , Swab Stefan
Published: July 2022

Background

Automated infrared pupillometry (AIP) and the Neurological Pupil index (NPi) provide an objective means of assessing and trending the pupillary light reflex (PLR) across a broad spectrum of neurological diseases. NPi quantifies the PLR and ranges from 0 to 5; in healthy individuals, the NPi of both eyes is expected to be ≥ 3.0 and symmetric. AIP values demonstrate emerging value as a prognostic tool with predictive properties that could allow practitioners to anticipate neurological deterioration and recovery. The presence of an NPi differential (a difference ≥ 0.7 between the left and right eye) is a potential sign of neurological abnormality.

Methods

We explored NPi differential by considering the modified Rankin Score at discharge (DC mRS) among patients admitted to neuroscience intensive care units (NSICU) of 4 U.S. and 1 Japanese hospitals and for two cohorts of brain injuries: stroke (including subarachnoid hemorrhage, intracerebral hemorrhage, acute ischemic stroke, and aneurysm, 1,200 total patients) and 185 traumatic brain injury (TBI) patients for a total of more than 54,000 pupillary measurements.

Results

Stroke patients with at least 1 occurrence of an NPi differential during their NSICU stay have higher DC mRS scores (3.9) compared to those without an NPi differential (2.7;P < .001). Patients with TBI and at least 1 occurrence of an NPi differential during their NSICU stay have higher discharge modified Rankin Scale scores (4.1) compared to those without an NPi differential (2.9;P < .001). When patients experience both abnormalities, abnormal (NPi < 3.0) and an NPi differential, the latter has an anticipatory relationship with respect to the former (P < .001 for z-score skewness analysis). Finally, our analysis confirmed ≥ 0.7 as the optimal cutoff value for the NPi differential (AUC = 0.71,P < .001).

Conclusion

The NPi differential is an important factor that clinicians should consider when managing critically ill neurological injured patients admitted to the neurocritical care units.

Trial registration

NCT02804438, Date of Registration: June 17, 2016.
Metabolic activity via 18F-FDG PET/CT is predictive of microsatellite instability status in colorectal cancer
Authors: Song Jinling , Li Zhongwu , Yang Lujing , Wei Maomao , Yang Zhi , Wang Xuejuan
Published: July 2022

Purpose

Identification of microsatellite instability high (MSI-H) colorectal cancer (CRC) is crucial for screening patients most likely to benefit from immunotherapy. We aim to investigate whether the metabolic characteristics is related to MSI status and can be used to predict the MSI-H CRC.

Methods

A retrospective analysis was conducted on 420 CRC patients who were identified via [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography(CT) prior to therapy. Maximum standardized uptake (SUVmax), mean standardized uptake (SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary tumor were calculated and compared between MSI-H and microsatellite stability (MSS). Predictive factors of MSI status were selected from metabolic parameters and clinicopathological profiles via a multivariate analysis.

Results

Of 420 colorectal cancers, 44 exhibited a high incidence of MSI. Both MTV and TLG were significantly higher in MSI-H group compared with the MSS group (P = 0.004 and P = 0.010, respectively). Logistic regression analysis indicated that CRC with MSI-H were related to younger age (P = 0.013), primary lesion located at right hemi-colon (P < 0.001) and larger MTV on PET/CT imaging (P = 0.019). MTV more than 32.19 of colorectal cancer was linked to the presence of MSI (P = 0.019).

Conclusion

Tumor metabolic burden were higher in MSI-H CRC which may be useful for predicting the MSI status of CRC patient and thus aid in determination of immunotherapy for patients with CRC.
Mycobacterium chimaera chorioretinitis preceding central nervous system lesions: a case report and review of the literature
Authors: Veenis Aaron , Haghnegahdar Megan , Ajlan Radwan
Published: July 2022

Background

Mycobacterium chimaera ocular infection is a rare disease that is linked to bypass devices used during cardiothoracic surgeries. Reported cases in the literature of ocular involvement preceding CNS involvement are based on clinical exam with no neuroimaging. Here we present a case of M. chimaera ocular infection with no CNS M. chimaera lesions on brain magnetic resonance imaging (MRI).

Case presentation

A 59-year-old female presented with altered mental status and blurred vision in February 2021. Her past medical history was significant for aortic valve replacement and ascending aortic aneurysm repair in 2017 complicated by known M. chimaera infection. She had been receiving azithromycin, ethambutol, rifampin, and amikacin as systemic anti-mycobacterium treatment. Her dilated fundus exam showed numerous yellow placoid circular lesions scattered throughout the macula and peripheral retina in both eyes with associated vitritis. Systemic workup, including brain MRI showed no acute infectious lesions. Her infections workup was unremarkable except for a positive toxoplasma IgM, for which she was treated with sulfamethoxazole/trimethoprim. One month later, a head computed tomography showed new numerous scattered round foci of hyperdensity throughout the cerebrum and brainstem thought to be foci of M. chimaera infection. Clofazimine was added per culture and sensitivity. MRI brain 1 month later showed mild decrease in conspicuity and number of these intensities while on anti-mycobacterium treatment. Her cognition had improved at that time as well. She was seen in retina clinic 2 months later where her exam showed similar retinal lesions with no associated vitritis or anterior chamber cell in bilateral eyes, suggesting a lack of active infection. Optical coherence tomography macula showed parafoveal cystoid macular edema bilaterally. She was started on steroidal and non-steroidal anti-inflammatory eye drops.

Conclusions

To the best of our knowledge, this is the first case in the literature to report M. chimaera chorioretinitis with concomitant negative neuroimaging. Chorioretinal M. chimaera lesions should motivate high suspicion of CNS involvement prompting early neurological work up.
Cholecysto-hepatic duct serving as the only drainage pathway of bile from the intrahepatic to the extrahepatic biliary system in an infant: a case report
Authors: Khoei Samin , Samani Payam Riahi , Fazelnia Faezeh , Pak Neda
Published: July 2022

Background

Cholecystohepatic duct is a rare anomaly of the biliary system which involves drainage of bile into the gallbladder which may be associated with agenesis of the common hepatic duct or common bile duct.

Case presentation

A 2.5-month-old infant presented to our emergency department with icterus. He had a history of esophageal atresia and imperforate anus which had been treated surgically by thoracotomy, esophagostomy, gastrostomy and colostomy placement. Following imaging studies by ultrasound and MRCP, the diagnosis of common hepatic duct agenesis was made. Cholecystohepatic duct was present as the solitary drainage pathway of bile from the intrahepatic to extrahepatic biliary system.

Conclusions

Cholecystohepatic ducts need a high index of suspicion to be diagnosed on preoperative hepatobiliary imaging. As they may be asymptomatic, they are predisposed to iatrogenic injury during hepatobiliary surgeries.
Impact of Event Scale-6 (IES-6) for U.S. adults who experienced the COVID-19 pandemic
Authors: Jeong Jiin , Kim Ah-Ram , Hilton Claudia , Hong Ickpyo
Published: July 2022

Background

COVID-19 pandemic causes psychological problems such as stress. It is important to accurately identify the level of stress and establish effective intervention. The Impact of Event Scale-6 (IES-6) is widely used for post-traumatic stress disorder (PTSD) screening by measuring the level of subjective stress, but there has been no research on its psychometric properties with individuals who experienced the COVID-19 pandemic.

Methods

A random sample of 600 participants were randomly selected from a COVID-19 survey database (n = 6391). Rasch analysis was conducted to examine item fit, rating scale structure, construct validity, differential item functioning (DIF), and precision of the IES-6.

Results

The principal component analysis of Rasch residuals (54.1% of the raw variance explained) and the average of residual correlations (average r = .19) supported the unidimensionality structure in the IES-6. The rating scale was suitable, and the item difficulty hierarchy was logical. The item fit and the DIF contrast were acceptable, except for item 5. The IES-6’s person reliability was .76, which was also an acceptable level.

Conclusions

This study showed that the IES-6 has acceptable item-level psychometrics for screening the stress level in adults in the United States for individuals who have experienced the COVID-19 pandemic. The findings suggested that the IES-6 would be useful for the rapid identification of the high-level stressand allow clinicians to quickly provide interventions for people with the COVID-19 related stress and their families.
Introducing a brain-computer interface to facilitate intraoperative medical imaging control – a feasibility study
Authors: Esfandiari Hooman , Troxler Pascal , Hodel Sandro , Suter Daniel , Farshad Mazda ,   Collaboration Group, Cavalcanti Nicola , Wetzel Oliver , Mania Sylvano , Cornaz Frederic , Selman Farah , Kabelitz Method , Zindel Christoph , Weber Sabrina , Haupt Samuel , Fürnstahl Philipp
Published: July 2022

Background

Safe and accurate execution of surgeries to date mainly rely on preoperative plans generated based on preoperative imaging. Frequent intraoperative interaction with such patient images during the intervention is needed, which is currently a cumbersome process given that such images are generally displayed on peripheral two-dimensional (2D) monitors and controlled through interface devices that are outside the sterile filed. This study proposes a new medical image control concept based on a Brain Computer Interface (BCI) that allows for hands-free and direct image manipulation without relying on gesture recognition methods or voice commands.

Method

A software environment was designed for displaying three-dimensional (3D) patient images onto external monitors, with the functionality of hands-free image manipulation based on the user’s brain signals detected by the BCI device (i.e., visually evoked signals). In a user study, ten orthopedic surgeons completed a series of standardized image manipulation tasks to navigate and locate predefined 3D points in a Computer Tomography (CT) image using the developed interface. Accuracy was assessed as the mean error between the predefined locations (ground truth) and the navigated locations by the surgeons. All surgeons rated the performance and potential intraoperative usability in a standardized survey using a five-point Likert scale (1 = strongly disagree to 5 = strongly agree).

Results

When using the developed interface, the mean image control error was 15.51 mm (SD: 9.57). The user's acceptance was rated with a Likert score of 4.07 (SD: 0.96) while the overall impressions of the interface was rated as 3.77 (SD: 1.02) by the users. We observed a significant correlation between the users' overall impression and the calibration score they achieved.

Conclusions

The use of the developed BCI, that allowed for a purely brain-guided medical image control, yielded promising results, and showed its potential for future intraoperative applications. The major limitation to overcome was noted as the interaction delay.
Midterm clinical outcomes of collateral ligament repair of the thumb and lesser digits: a retrospective analysis of 35 cases
Authors: Sahin Mehmet Sukru
Published: July 2022

Background

Finger collateral ligament injuries are common, and conservative treatment usually works well. However, complete ruptures that lead to instability could cause painful disability. This study presents our clinical experience and a qualitative functional evaluation following the surgical repair of the thumb and proximal interphalangeal (PIP) joint collateral ligament ruptures.

Methods

Thirty-five patients (22 men and 13 women), diagnosed via a physical examination and magnetic resonance imaging (MRI) with a total collateral ligament rupture in the metacarpophalangeal thumb (16) and PIP joints of the lesser digits (19) and treated surgically, were evaluated retrospectively. The limited range of motion; functional score by Saetta; disabilities of the arm, shoulder, and hand (DASH) score; pre- and post-operative pain, deformity level; and post-operative ability to grip keys, buttons, and jars were measured. The significance of the change between the pre and post-operative visual analog scale for pain (VAS) scores were evaluated using the Wilcoxon signed-rank test. The difference between the lesser digits and thumb groups by patient age was evaluated using the Mann–Whitney-U test. All data, such as the mean, range, and standard deviation, were calculated using SPSS.

Results

The mean pre- and post-operative VAS scores were 4.8 (from 3 to 7) and 0.91 (0 to 4), respectively. The mean post-operative limitation in the range of motion was 9.78° (s = 14.47) for lesser digits and 6.87° (s = 12.29) for the thumb. According to Seatta et al., the final functional score was 62.5% excellent, 25% good, and 12.5% moderate for the thumb and 84.2% excellent, 10.5% good, and 5.3% poor for the lesser digits. The mean post-operative DASH score was 13.55 (SD: 8.77) for lesser digits and 14.22 (SD: 8.9) for the thumb. The mean contralateral (healthy) hand DASH score was 0.75 (SD: 1.05) for lesser digits and 0.75 (SD: 1.05) for the thumb. For the thumb and lesser digits, thez-scores were − 3.55 and − 3.787, respectively, and the progress of the VAS score was significant (p < 0.05).

Conclusion

After a 40-month follow-up for 35 acute, subacute, and chronic cases, the results suggest that direct and suture-anchor repairs are feasible, painless treatments associated with good finger function.
Temporizing cast immobilization is a safe alternative to external fixation in ankle fracture-dislocation while posterior malleolar fragment size predicts loss of reduction: a case control study
Authors: Gerlach Rene , Toepfer Andreas , Jacxsens Matthijs , Zdravkovic Viliam , Potocnik Primoz
Published: July 2022

Background

To determine if temporizing cast immobilization is a safe alternative to external fixator (ex-fix) in ankle fracture-dislocations with delayed surgery or moderate soft-tissue injury, we analysed the early complications and re-dislocation rates of cast immobilization in relation to ex-fix in patients sustaining these injuries.

Methods

All skeletally mature patients with a closed ankle fracture-dislocation and a minimum 6-months follow-up treated between 2007 and 2017 were included. Baseline demographics, comorbidities, injury description, treatment history and complications were assessed.

Results

In 160 patients (94 female; mean age 50 years) with 162 ankle fracture-dislocations, 35 underwent primary ex-fix and 127 temporizing cast immobilizations. Loss of reduction (LOR) was observed in 25 cases (19.7%) and 19 (15.0%) were converted to ex-fix. The rate of surgical site infections (ex-fix: 11.1% vs cast: 4.6%) and skin necrosis (ex-fix: 7.4% vs cast: 6.5%) did not differ significantly between groups (p = 0.122 and p = 0.825). Temporizing cast immobilization led to an on average 2.7 days earlier definite surgery and 5.0 days shorter hospitalization when compared to ex-fix (p < 0.001). Posterior malleolus fragment (PMF) size predicted LOR with ≥ 22.5% being the threshold for critical PMF-size (p < 0.001).

Conclusion

Temporizing cast immobilization was a safe option for those ankle fracture-dislocations in which immediate definite treatment was not possible. Those temporized in a cast underwent definite fixation earlier than those with a fix-ex and had a complication rate no worse than the ex-fix patients. PMF-size was an important predictor for LOR. Primary ex-fix seems appropriate for those with ≥ 22.5% PMF-size.

Trial registration

The study does not meet the criteria of a prospective, clinical trial. There was no registration.
Ultrasound gray scale ratio for differential diagnosis of papillary thyroid microcarcinoma from benign micronodule in patients with Hashimoto’s thyroiditis
Authors: Han Zhijiang , Xie Lesi , Wei Peiying , Lei Zhikai , Ding Zhongxiang , Zhang Ming
Published: July 2022

Background

To investigate the diagnostic value of ultrasound gray scale ratio (UGSR) in differentiating papillary thyroid microcarcinomas (PTMCs) from benign micronodules (BMNs) in patients with Hashimoto’s thyroiditis (HT).

Methods

The ultrasound images of 285 PTMCs (from 247 patients) and 173 BMNs (from 140 patients) in the HT group, as well as 461 PTMCs (from 417 patients) and 234 BMNs (from 197 patients) in the non-HT group were retrospectively analyzed. The diagnosis of all cases was confirmed by histopathological examinations. The gray scale values of the nodules and surrounding thyroid tissues were measured and subsequently the UGSRs were calculated. Receiver operating characteristic curve analysis was used to determine the area under the curve (AUC), optimal UGSR threshold, sensitivity and specificity in differentiating PTMCs and BMNs in the two groups.

Results

The UGSR of PTMC and BMN was 0.52 ± 0.12 and 0.85 ± 0.24 in the HT group (P < 0.001), and 0.57 ± 0.13 and 0.87 ± 0.20 in the non-HT group (P < 0.001), respectively. The difference in PTMC-UGSR was significant between the two groups (P < 0.001), whereas BMN-UGSR did not differ between the two groups (P = 0.416). The AUC, optimal UGSR threshold, sensitivity and specificity of UGSR for differentiating PTMC and BMN in the HT and non-HT group were 0.890 versus 0.901, 0.68 versus 0.72, 91.23% versus 90.67%, and 77.46% versus 82.05%, respectively.

Conclusions

The USGR of the HT group was lower than that of the non-HT group.

Moreover, UGSR exhibited important diagnostic value in differentiating PTMC from BMN in both HT and non-HT groups.
Dimethyl fumarate improves cognitive impairment by enhancing hippocampal brain-derived neurotrophic factor levels in hypothyroid rats
Authors: Pan Haiyan , Wang Yanbo , Wang Xiaowei , Yan Ci
Published: July 2022

Background

Dimethyl fumarate (DMF) is an effective drug for multiple sclerosis and can improve the cognitive dysfunction caused by streptozotocin, but the effect on cognitive dysfunction caused by hypothyroidism is unclear.

Methods

After the hypothyroidism rat model induced by propylthiouracil, we gave rats 25 mg/kg DMF by gavage. The body weight during model building and administration was recorded. The levels of T4 and T3 in serum were detected by an automatic biochemical analyzer. Morris water maze test was used to detect the effect of DMF on cognitive learning ability. The effect of DMF on Nissl bodies in the brain tissue was evaluated by Nissl staining. The mRNA and protein levels of BDNF in brain tissue were detected by quantitative reverse transcription-polymerase chain reaction and Western blot. The degrees of p-AKT/AKT and p-CREB/CREB in brain tissue were detected by Western blot.

Results

After DMF treatment, the body weight of hypothyroid rats recovered, and the levels of T3 and T4 in the serum were ameliorated. DMF also reduced the escape latency and distance traveled, and increased the swim speed. The number of Nissl bodies and expression of BDNF, p-AKT/AKT, and p-CREB/CREB in the brain tissue were increased after DMF treatment.

Conclusion

DMF improved the cognitive dysfunction of hypothyroid rats by increasing the level of BDNF in the brain tissue of hypothyroid rats.
Comparison of alveolar bone width and sagittal tooth angulation of maxillary central incisors in Class I and Class III canine relationships: a retrospective study using CBCT
Authors: Lei Chen , Yu Qun , Wu Di , Cai Kunzhan , Weigl Paul , Tang Chunbo
Published: July 2022

Background

Canine relationship is a key reference identifying anterior malocclusion and an important implication for evaluating preimplantation bone morphology at maxillary esthetic zone. This study aimed to compare the differences of maxillary central incisor-related measurements (alveolar bone thickness and tooth sagittal angulation) between Class I and Class III canine relationship and further explore the risk factors for immediate implant placement in the anterior maxilla based on cone beam computed tomography (CBCT) data.

Methods

CBCT digital imaging and communications in medicine (DICOM) files of 107 patients (54 with Class I canine relationship and 53 with Class III canine relationship) were collected and the alveolar bone thickness at mid-root (mid-root buccal thickness/MBT; palatal/MPT), apical regions (apical buccal thickness/ABT; palatal/APT) and sagittal angulation (SA) of the maxillary central incisor at the examined side were measured on the mid-sagittal observation plane. Descriptive statistical analysis and frequency distributions of the measurements based on Class I or Class III canine relationship were established. Statistical analyses were performed using Fisher’s exact test, independent samples t test and Pearson correlation test with the significance level set at p < 0.05.

Results

The frequency distributions of maxillary central incisors’ MPT, ABT, APT and SA showed significant differences between Class I and Class III canine relationships (p = 0.030, 0.024, 0.000 and 0.000, respectively). MPT (2.48 ± 0.88 mm vs. 3.01 ± 1.04 mm, p = 0.005), APT (6.79 ± 1.65 mm vs. 8.47 ± 1.93 mm, p = 0.000) and SA (12.23 ± 5.62° vs. 16.42 ± 4.49°, p = 0.000) were significantly smaller in patients with Class III canine relationship. Moreover, SA showed a strong positive correlation with APT (R = 0.723, p = 0.000) and a moderate negative correlation with ABT (R = − 0.554, p = 0.000).

Conclusions

In populations with Class III canine relationship, maxillary central incisors were significantly more labially inclined and have a thinner palatal bone plate at the apex compared with Class I relationship. Clinicians should avoid palatal perforation during immediate implantation at sites of originally protrusive maxillary incisors.
Prevalence and associated factors of early sexual initiation among female youth in East Africa: further analysis of recent demographic and health survey
Authors: Hailegebreal Samuel , Gilano Girma , Seboka Binyam Tariku , Sidelil Habile , Awol Shekur Mohammed , Haile Yosef , Simegn Atsedu Endale , Haile Firehiwot
Published: July 2022

Background

Early sexual initiation is one of the risky sexual practices. Early sexual beginning is associated with an increased risk of HIV/AIDS, sexually transmitted infections (STIs), unexpected pregnancies, unsafe abortion, premature deliveries, and psychosocial issues. However, there is still a lack of evidence, particularly in East Africa, where community-level factors are not investigated. Therefore, this study aimed to estimate the pooled prevalence and to identify associated factors of early sexual initiation among female youth in Eastern Africa.

Methods

A total weighted sample of 49,716 female youth was included in this analysis. STATA version 14 software was used for data extraction, recoding, and analysis. A multilevel binary logistic regression model was fitted to identify determinants of early sexual initiation in the region. Finally, Adjusted Odds Ratio (AOR) with a 95% Confidence Interval (CI) was reported to declare the factors that are significantly associated with early sexual initiation.

Result

The prevalence of early sexual initiation in East Africa was 21.14% [95% CI: 20.00%, 21.50%]. In the multivariable multilevel analysis; being age 20–24 years [AOR = 0.65: 95% CI; 0.61, 0.69], primary [AOR = 0.73: 95% CI; 0.67, 0.78], secondary &above education [AOR = 0.30: 95% CI; 0.27,0.33], married [AOR = 1.85: 95% CI; 1.73,1.97], middle wealth [AOR = 0.78: 95% CI; 0.72,0.84], richest [AOR = 0.74: 95% CI; 0.68,0.80], and reading newspaper [AOR 0.77: 95% CI;0.71,0.83] were significantly associated with early sexual initiation.

Conclusion

The study revealed that early sexual initiation among female youth was high in East Africa. Educational status, respondent age, marital status, wealth index, age at first cohabitation, contraceptive use, reading newspaper, and place of residence were associated with early sexual initiation. Therefore, the survey findings will help policymakers, as well as governmental and non-governmental organizations, design the most effective interventions. Moreover, strengthening information, education, and wealth status are important intervention areas to delay the age of early sexual debut.
Complex skills are required for new primary health care researchers: a training program responds
Authors: Terry Amanda L. , Stewart Moira , Ashcroft Rachelle , Brown Judith Belle , Burge Fred , Haggerty Jeannie , McWilliam Carol , Meredith Leslie , Reid Graham J. , Thomas Roanne , Wong Sabrina T. ,   and the TUTOR-PHC Program Investigators/Mentors, Van Hoorn Robert
Published: July 2022

Background

Current dimensions of the primary health care research (PHC) context, including the need for contextualized research methods to address complex questions, and the co-creation of knowledge through partnerships with stakeholders – require PHC researchers to have a comprehensive set of skills for engaging effectively in high impact research.

Main body

In 2002 we developed a unique program to respond to these needs - Transdisciplinary Understanding and Training on Research - Primary Health Care (TUTOR-PHC). The program’s goals are to train a cadre of PHC researchers, clinicians, and decision makers in interdisciplinary research to aid them in tackling current and future challenges in PHC and in leading collaborative interdisciplinary research teams. Seven essential educational approaches employed by TUTOR-PHC are described, as well as the principles underlying the curriculum. This program is unique because of its pan-Canadian nature, longevity, and the multiplicity of disciplines represented. Program evaluation results indicate: 1) overall program experiences are very positive; 2) TUTOR-PHC increases trainee interdisciplinary research understanding and activity; and 3) this training assists in developing their interdisciplinary research careers. Taken together, the structure of the program, its content, educational approaches, and principles, represent a complex whole. This complexity parallels that of the PHC research context – a context that requires researchers who are able to respond to multiple challenges.

Conclusion

We present this description of ways to teach and learn the advanced complex skills necessary for successful PHC researchers with a view to supporting the potential uptake of program components in other settings.
Hospital physicians´ working hour characteristics and sleep quality: a cross-sectional analysis of realized working hour and survey data
Authors: Karhula Kati , Koskinen Aki , Ervasti Jenni , Hakola Tarja , Isoviita Veli-Matti , Kivimäki Ilkka , Puttonen Sampsa , Oksanen Tuula , Härmä Mikko
Published: July 2022

Background

Hospital physicians’ work includes on-call duties to provide 24/7 health care. Previous studies using self-reported survey data have associated long working hours and on-call work with sleep difficulties. To reduce recall bias, we complemented survey data with payroll-based objective data to study whether hospital physicians’ realized working hours are associated with sleep.

Methods

The study was nested within the Finnish Public Sector study. We used survey data on 728 hospital physicians (mean age 43.4 years, 62% females) from 2015 linked to realized daily working hour data from 3 months preceding the survey. The associations of working hour characteristics with sleep quantity and quality were studied with multinomial logistic regression analysis adjusted for demographics, overall stressfulness of life situation, control over scheduling of shifts, and hospital district.

Results

One fourth (26%) of the participants reported short (≤6.5 h) average sleep duration. Frequent night work (> 6 shifts/91 days) was associated with short sleep (OR 1.87 95%CI 1.23–2.83) compared to no night work. Approximately one third (32%) of the physicians reported insufficient sleep. Physicians with long weekly working hours (> 48 hours) had higher odds for insufficient sleep (OR 1.78 95%CI 1.15–2.76) than physicians with short weekly working hours (< 40 hours). Insufficient sleep was also associated with frequent on-call duties (> 12 shifts/3 months OR 2.00 95%CI 1.08–3.72), frequent night work (OR 1.60 95%CI 1.09–2.37), and frequent short shift intervals (≤11 hours; > 12 times/3 months OR 1.65 95%CI 1.01–2.69) compared to not having these working hour characteristics. Nearly half of the physicians (48%) reported at least one sleep difficulty at least two times a week and frequent night work increased odds for difficulties in initiating sleep (OR 2.43 95%CI 1.04–5.69). Otherwise sleep difficulties were not associated with the studied working hour characteristics.

Conclusion

We used realized working hour data to strengthen the evidence on on-call work and sleep quality and our results advice to limit the frequency of night work, on-call shifts, short shift intervals and long weekly working hours to promote hospital physicians’ sufficient sleep.
Homologous recombination deficiency (HRD) score in aggressive prostatic adenocarcinoma with or without intraductal carcinoma of the prostate (IDC-P)
Authors: Zhu Sha , Zhao Jinge , Nie Ling , Yin Wenlian , Zhang Yaowen , Zhao Fengnian , Ni Yuchao , Zhang Xingming , Wang Zhipeng , Dai Jindong , Liu Zhenhua , Chen Junru , Zeng Yuhao , Wang Zilin , Sun Guangxi , Liang Jiayu , Zhao Xiaochen , Zhu Xudong , Tao Ronggui , Yang Jiyu , He Ben , Chen Ni , Shen Pengfei , Zeng Hao
Published: July 2022

Background

Intraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially unstable genome. Homologous recombination deficiency (HRD) score is a result-oriented method to describe the genomic instability status. This study investigates the association of HRD scores with IDC-P and other clinicopathological factors and the prognostic implication of HRD scores in an aggressive prostate cancer cohort.

Methods

This study involved 123 PCa patients, including high-risk localized (M0) and de novo metastatic (M1) diseases. HRD score is calculated based on over 10,000 single-nucleotide polymorphisms distributed across the human genome. We explored the association between HRD scores and clinicopathological characteristics, genomic alterations, and patients’ prognoses using rank-sum tests, chi-square tests, Kaplan-Meier curves, and Cox proportional hazards method.

Results

The median HRD score of this cohort is 21.0, with 65 (52.8%) patients showing HRD score≥21. Tumors with IDC-P displayed higher HRD scores than adenocarcinoma (P=0.002); other high HRD score-related factors included M1 (P =0.008) and high ISUP grades (4–5) (P=0.001). MYC mutations were associated with high HRD scores (P<0.001) in the total cohort. TP53 mutations (P=0.010) and HRR pathway mutations (P=0.028) corresponded to high HRD scores in IDC-P positive and non-IDC-P patients, respectively, but not vice versa. HRD scores higher than 21 indicated significantly worse survival in the total cohort.

Conclusions

M1, high Gleason score, and IDC-P pathology represent higher HRD scores in PCa. Tumors with IDC-P might have different driven mechanisms for high HRD scores than non-IDC-P. HRD score displayed prognostic value in this aggressive prostate cancer cohort.
Leptospirosis vaccination in dogs attending UK primary care practices: vaccine uptake and factors associated with administration
Authors: Taylor Collette , O’Neill Dan G. , Catchpole Brian , Brodbelt Dave C.
Published: July 2022

Background

Leptospirosis is a zoonotic disease that is found globally and affects most mammalian species. Vaccination of dogs against leptospirosis is an important approach to preventing clinical disease, or reducing disease severity, as well as reducing transmission of the infection to humans. Although it is generally considered to be a ‘core’ vaccine, there is limited information on the level of leptospirosis vaccine usage and factors associated with its usage in dogs in the UK. The study aimed to report the uptake of leptospirosis vaccination and factors associated with its usage in a cohort of dogs under primary veterinary care during a 12-month period.

Results

From a population of 905,543 dogs, 49% (95%CI 48.9–49.1%) had at least one leptospirosis vaccine administered during the 12 months of study. Adult dogs had reduced odds of receiving a leptospirosis vaccine when compared to dogs < 1 year old, with dogs > 8 years old having a greater than ten-fold reduction in odds (OR = 0.08, 95%CI 0.07–0.09). Odds of receiving a leptospirosis vaccine was increased in insured dogs when compared to uninsured dogs (OR = 1.22, 95%CI = 1.17–1.28). Neutered dogs had reduced odds of receiving a leptospirosis vaccine (OR = 0.87, 95%CI 0.83–0.91). Breed associations with receiving a leptospirosis vaccine varied. Several breeds were associated with increased odds of receiving a leptospirosis vaccine when compared to crossbreed dogs, including Border Terriers (OR = 1.49, 95%CI 1.42–1.57), Golden Retrievers (OR = 1.30, 95%CI = 1.24–1.37), Cocker Spaniels (OR = 1.27, 95%CI 1.23–1.31) and West Highland White Terriers (OR = 1.27, 95%CI 1.22–1.31). French Bulldogs (OR = 0.64, 95%CI = 0.62–0.67), Staffordshire Bull Terriers (OR = 0.79, 95%CI 0.78–0.82) and Pugs (OR = 0.91, 95%CI =0.88–0.95) had significantly reduced odds of receiving a leptospirosis vaccination during the study.

Conclusion

This work identified that almost half of the UK primary care attending population received a leptospirosis vaccine during the year. Several demographic variables were associated with leptospirosis vaccine administration, with age being particularly important. Both the proportion of uptake and factors associated with leptospirosis vaccine usage can be used as a benchmark for comparisons in the future. Additionally, an understanding of which populations have reduced odds of receiving a leptospirosis vaccine can potentially be used for initiatives to encourage owner vaccination uptake in these groups.
Exosomes-based therapy of stroke, an emerging approach toward recovery
Authors: Seyedaghamiri Fatemehsadat , Salimi Leila , Ghaznavi Dara , Sokullu Emel , Rahbarghazi Reza
Published: July 2022

Based on clinical observations, stroke is touted as one of the specific pathological conditions, affecting an individual’s life worldwide. So far, no effective treatment has been introduced to deal with stroke post-complications. Production and release of several neurotrophic factors by different cells exert positive effects on ischemic areas following stroke. As a correlate, basic and clinical studies have focused on the development and discovery of de novo modalities to introduce these factors timely and in appropriate doses into the affected areas. Exosomes (Exo) are non-sized vesicles released from many cells during pathological and physiological conditions and participate in intercellular communication. These particles transfer several arrays of signaling molecules, like several neurotrophic factors into the acceptor cells and induce specific signaling cascades in the favor of cell bioactivity. This review aimed to highlight the emerging role of exosomes as a therapeutic approach in the regeneration of ischemic areas.
Expression of voltage-gated Ca2+ channels, Insp3Rs, and RyRs in the immature mouse ovary
Authors: Bahena-Alvarez Daniel , Millan-Aldaco Diana , Rincón-Heredia Ruth , Escamilla-Avila Nancy , Hernandez-Cruz Arturo
Published: July 2022

Background

The postnatal mammalian ovary undergoes a series of changes to ensure the maturation of sufficient follicles to support ovulation and fecundation over the reproductive life. It is well known that intracellular [Ca2+]i signals are necessary for ovulation, fertilization, and egg activation. However, we lack detailed knowledge of the molecular identity, cellular distribution, and functional role of Ca2+ channels expressed during folliculogenesis. In the neonatal period, ovarian maturation is controlled by protein growth factors released from the oocyte and granulosa cells. Conversely, during the early infantile period, maturation becomes gonadotropin-dependent and is controlled by granulosa and theca cells. The significance of intracellular Ca2+ signaling in folliculogenesis is supported by the observation that mice lacking the expression of Ca2+/calmodulin-dependent kinase IV in granulosa cells suffer abnormal follicular development and impaired fertility.

Results

Using immunofluorescence in frozen ovarian sections and confocal microscopy, we assessed the expression of high-voltage activated Ca2+ channel alpha subunits and InsP3 and ryanodine receptors in the postnatal period from 3 to 16 days. During the neonatal stage, oocytes from primordial and primary follicles show high expression of various Ca2+-selective channels, with granulosa and stroma cells expressing significantly less. These channels are likely involved in supporting Ca2+-dependent secretion of peptide growth factors. In contrast, during the early and late infantile periods, Ca2+ channel expression in the oocyte diminishes, increasing significantly in the granulosa and particularly in immature theca cells surrounding secondary follicles.

Conclusions

The developmental switch of Ca2+ channel expression from the oocytes to the perifollicular cells likely reflects the vanishing role of the oocytes once granulosa and theca cells take control of folliculogenesis in response to gonadotropins acting on their receptors.
Assessing the clinical utility of protein structural analysis in genomic variant classification: experiences from a diagnostic laboratory
Authors: Caswell Richard C. , Gunning Adam C. , Owens Martina M. , Ellard Sian , Wright Caroline F.
Published: July 2022

Background

The widespread clinical application of genome-wide sequencing has resulted in many new diagnoses for rare genetic conditions, but testing regularly identifies variants of uncertain significance (VUS). The remarkable rise in the amount of genomic data has been paralleled by a rise in the number of protein structures that are now publicly available, which may have clinical utility for the interpretation of missense and in-frame insertions or deletions.

Methods

Within a UK National Health Service genomic medicine diagnostic laboratory, we investigated the number of VUS over a 5-year period that were evaluated using protein structural analysis and how often this analysis aided variant classification.

Results

We found 99 novel missense and in-frame variants across 67 genes that were initially classified as VUS by our diagnostic laboratory using standard variant classification guidelines and for which further analysis of protein structure was requested. Evidence from protein structural analysis was used in the re-assessment of 64 variants, of which 47 were subsequently reclassified as pathogenic or likely pathogenic and 17 remained as VUS. We identified several case studies where protein structural analysis aided variant interpretation by predicting disease mechanisms that were consistent with the observed phenotypes, including loss-of-function through thermodynamic destabilisation or disruption of ligand binding, and gain-of-function through de-repression or escape from proteasomal degradation.

Conclusions

We have shown that using in silico protein structural analysis can aid classification of VUS and give insights into the mechanisms of pathogenicity. Based on our experience, we propose a generic evidence-based workflow for incorporating protein structural information into diagnostic practice to facilitate variant classification.
Grey matter changes on brain MRI in subjective cognitive decline: a systematic review
Authors: Arrondo Pablo , Elía-Zudaire Óscar , Martí-Andrés Gloria , Fernández-Seara María A. , Riverol Mario
Published: July 2022

Introduction

People with subjective cognitive decline (SCD) report cognitive deterioration. However, their performance in neuropsychological evaluation falls within the normal range. The present study aims to analyse whether structural magnetic resonance imaging (MRI) reveals grey matter changes in the SCD population compared with healthy normal controls (HC).

Methods

Parallel systematic searches in PubMed and Web of Science databases were conducted, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Quality assessment was completed using the Newcastle-Ottawa Scale (NOS).

Results

Fifty-one MRI studies were included. Thirty-five studies used a region of interest (ROI) analysis, 15 used a voxel-based morphometry (VBM) analysis and 10 studies used a cortical thickness (CTh) analysis. Ten studies combined both, VBM or CTh analysis with ROI analysis.

Conclusions

Medial temporal structures, like the hippocampus or the entorhinal cortex (EC), seemed to present grey matter reduction in SCD compared with HC, but the samples and results are heterogeneous. Larger sample sizes could help to better determine if these grey matter changes are consistent in SCD subjects.
Pancreatic stone protein point-of-care testing can reduce healthcare expenditure in sepsis
Authors: Schneider John E. , Dick Katherine , Cooper Jacie T. , Chami Nadine
Published: July 2022

Background

Sepsis is a life-threatening organ dysfunction in response to infection. Early recognition and rapid treatment are critical to patient outcomes and cost savings, but sepsis is difficult to diagnose because of its non-specific symptoms. Biomarkers such as pancreatic stone protein (PSP) offer rapid results with greater sensitivity and specificity than standard laboratory tests.

Methods

This study developed a decision tree model to compare a rapid PSP test to standard of care in the emergency department (ED) and intensive care unit (ICU) to diagnose patients with suspected sepsis. Key model parameters included length of hospital and ICU stay, readmission due to infection, cost of sepsis testing, length of antibiotic treatment, antibiotic resistance, and clostridium difficile infections. Model inputs were determined by review of sepsis literature.

Results

The rapid PSP test was found to reduce costs by $1688 per patient in the ED and $3315 per patient in the ICU compared to standard of care. Cost reductions were primarily driven by the specificity of PSP in the ED and the sensitivity of PSP in the ICU.

Conclusions

The results of the model indicate that PSP testing is cost saving compared to standard of care in diagnosis of sepsis. The abundance of sepsis cases in the ED and ICU make these findings important in the clinical field and further support the potential of sensitive and specific markers of sepsis to not only improve patient outcomes but also reduce healthcare expenditures.
Regulatory T cells-centered regulatory networks of skeletal muscle inflammation and regeneration
Authors: Chen Ziyu , Lan HaiQiang , Liao ZhaoHong , Huang JingWen , Jian XiaoTing , Hu Jijie , Liao Hua
Published: July 2022

As the understanding of skeletal muscle inflammation is increasingly clarified, the role of Treg cells in the treatment of skeletal muscle diseases has attracted more attention in recent years. A consensus has been reached that the regulation of Treg cells is the key to completing the switch of inflammation and repair of skeletal muscle, whose presence directly determine the repairing quality of the injured skeletal muscle. However, the functioning process of Treg cells remains unreported, thereby making it necessary to summarize the current role of Treg cells in skeletal muscle. In this review, the characteristics, origins, and cellular kinetics of these Treg cells are firstly described; Then, the relationship between Treg cells and muscle satellite cells (MuSCs), conventional T cells (Tconv) is discussed (the former is involved in the entire repair and regeneration process, while the latter matters considerably in causing most skeletal muscle autoimmune diseases); Next, focus is placed on the control of Treg cells on the phenotypic switch of macrophages, which is the key to the switch of inflammation; Finally, factors regulating the functional process of Treg cells are analyzed, and a regulatory network centered on Treg cells is summarized. The present study summarizes the cell-mediated interactions in skeletal muscle repair over the past decade, and elucidates the central role of regulatory T cells in this process, so that other researchers can more quickly and comprehensively understand the development and direction of this very field. It is believed that the hereby proposed viewpoints and problems can provide fresh visions for the latecomers.