bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinal cytotoxicity of silica and titanium dioxide nanoparticles
Authors: Park Joo-Hee , Kim Dong Ju , Park Choul Yong 
Published: November 2021

Abstract
The retina plays a key role in human vision. It is composed of cells that are essential for vision signal generation. Thus far, conventional medications have been ineffective for treating retinal diseases because of the intrinsic blood–retinal barrier. Nanoparticles (NPs) are promising effective platforms for ocular drug delivery. However, nanotoxicity in the retinal tissue has not received much attention. This study used R28 cells (a retinal precursor cell line that originated from rats) to investigate the safety of two commonly used types of NPs: silica nanoparticles (SiO2NPs, 100 nm) and titanium dioxide nanoparticles (TiO2NPs, 100 nm). Cellular viability and reactive oxygen species generation were measured after 24, 48, and 72 h of exposure to each NP. Cellular autophagy and the mTOR pathways were evaluated. The retinal toxicity of the NPs was investigated in vivo in rat models. Both types of NPs were found to induce significant dose-dependent toxicity on the R28 cells. A significant elevation of reactive oxygen species generation was also observed. Increased autophagy and decreased mTOR phosphorylation were observed after SiO2NPs and TiO2NPs exposure. The diffuse apoptosis of the retinal cellular layers was detected after intravitreal injection.
Evaluating the glucagon-like peptide-1 receptor in managing asthma
Authors: Wu Ashley Y. , Cahill Katherine N. , Toki Shinji , Peebles R. Stokes 
Published: November 2021

Purpose of review
The aim of this study was to discuss the role of glucagon-like peptide-1 (GLP-1) receptor signalling in reducing lung inflammation and potential use for GLP-1 receptor agonists (GLP-1RAs) in management of asthma.

Recent findings
Although GLP-1RA are currently used for the treatment of type 2 diabetes (T2D) and weight loss in obesity, there is much interest in expanding the indications for use in other diseases, including inflammatory pulmonary disease. In animal models of both acute and chronic pulmonary disease, use of GLP-1RA reduces airway inflammation, obstruction and fibrosis. In particular, GLP-1 receptor (GLP-1R) signalling seems to inhibit allergen-induced type 2 inflammation, making it an attractive agent for asthma. Results are especially promising in disease processes with disturbed metabolic regulation, such as T2D or metabolic syndrome. Retrospective clinical studies demonstrate promising evidence for the use of GLP-1RAs in comorbid diabetes and asthma, although prospective human studies are limited.

Summary
Here, we discuss the biology of GLP-1 and GLP-1R signalling, review the preclinical and mechanistic evidence for how GLP-1R signalling may reduce pulmonary inflammation, and summarize recent and upcoming clinical studies. Ultimately, targeting GLP-1R signalling may represent a novel approach for asthma therapy that is glucocorticoid sparing and possibly disease modifying.
The Importance of Extended High-Frequency Speech Information in the Recognition of Digits, Words, and Sentences in Quiet and Noise
Authors: Polspoel Sigrid , Kramer Sophia E. , van Dijk Bas , Smits Cas 
Published: November 2021

Objectives:
In pure-tone audiometry, hearing thresholds are typically measured up to 8 kHz. Recent research has shown that extended high-frequency (EHF; frequencies >8 kHz) speech information improves speech recognition. However, it is unclear whether the EHF benefit is present for different types of speech material. This study assesses the added value of EHF information for speech recognition in noise for digit triplets, consonant–vowel–consonant (CVC) words, and sentences; and for speech recognition in quiet for CVC.

Design:
Twenty-four young adults with normal-hearing thresholds up to 16 kHz performed a listening experiment in quiet and in noise in a within-subject repeated measures design. Stimuli were presented monaurally. Steady state speech-shaped noise at a fixed signal to noise ratio was used for measurements in noise. Listening conditions varied only in terms of available EHF information. Stimuli were presented in three different conditions: (1) both speech and noise broadband, (2) speech broadband and noise low-pass filtered at 8 kHz, and (3) both speech and noise low-pass filtered at 8 kHz. In the speech-in-quiet experiment, stimuli (CVC) were high-pass filtered at 3 kHz and presented in two conditions: (1) with EHF information and (2) without EHF information.

Results:
In the speech-in-noise experiment, for all speech material, the highest scores were achieved in the condition where the noise was low-pass filtered at 8 kHz and speech unfiltered; the lowest scores were obtained in the condition where both speech and noise were low-pass filtered at 8 kHz. Adding speech frequencies above 8 kHz improved the median recognition scores by 75.0%, 21.8%, and 23.8% for digit triplets, words, and sentences, respectively, at a fixed signal to noise ratio. In the speech-in-quiet experiment, median recognition scores were 7.8% higher in the condition where the EHF information was available, as opposed to when it was not.

Conclusions:
Speech information for frequencies above 8 kHz contributes to speech recognition in noise. It also contributes to speech recognition in quiet when information below 3 kHz is absent. Our results suggest that EHFs may be relevant in challenging listening conditions and should be measured in pure-tone audiometry to get a complete picture of a person’s hearing. Further, results of speech recognition tests may vary when different recording and/or measurement equipment is used with different frequency responses above 8 kHz.
An Economic Evaluation of Australia’s Newborn Hearing Screening Program: A Within-Study Cost-Effectiveness Analysis
Authors: Sharma Rajan , Gu Yuanyuan , Sinha Kompal , Ching Teresa Y. C. , Marnane Vivienne , Gold Lisa , Wake Melissa , Wang Jing , Parkinson Bonny 
Published: November 2021

Objectives:
Hearing loss is one of the most prevalent congenital disorders among children. Many countries have implemented universal newborn hearing screening (UNHS) for the early diagnosis and treatment of hearing loss. Despite widespread implementation, the value for money of UNHS is unclear due to lack of cost and outcomes data from rigorous study designs. The objective of this research is to conduct a within-study cost-effectiveness analysis of UNHS compared with targeted screening (targeting children with risk factors of hearing loss) from the Australian healthcare system perspective. This evaluation is the first economic evaluation to assess the cost-effectiveness of UNHS compared to targeted screening using real-world data from a natural experiment.

Design:
The evaluation assumed the Australian healthcare system perspective and considered a time horizon of 5 years. Utilities were estimated using responses to the Health Utilities Index Mark III. Screening costs were estimated based on the Victorian Infant Hearing Screening Program. Ongoing costs were estimated based on administrative data, while external data sources were used to estimate costs related to hearing services. Missing data were handled using the multiple imputation method. Outcome measures included quality-adjusted life years (QALYs) and four language and communication-related outcomes: Peabody Picture Vocabulary Test, Wechsler Nonverbal Scale of Ability, Progressive Achievement Test, and comprehensive, expressive, and total language scores based on the Preschool Language Scale.

Results:
On average, the UNHS cost an extra Australian dollar (A$)22,000 per diagnosed child and was associated with 0.45 more QALYs per diagnosed child compared with targeted screening to 5 years, resulting in an incremental cost-effectiveness ratio (ICER) of A$48,000 per QALY gained. The ICERs for language outcomes lay between A$3,900 (for expressive language score) and A$83,500 per one-point improvement in language score (for Wechsler Nonverbal Scale of Ability). UNHS had a 69% probability of being more cost-effective compared to targeted screening at a willingness to pay threshold of A$60,000 per QALY gained. ICERs were most sensitive to the screening costs.

Conclusions:
The evaluation demonstrated the usefulness of a within-study economic evaluation to understand the value for money of the UNHS program in the Australian context. Findings from this evaluation suggested that screening costs were the key driver of cost-effectiveness results. Most outcomes were not significantly different between UNHS and targeted screening groups. The ICER may be overestimated due to the short follow-up period. Further research is warranted to include long-term resource use and outcome data, late diagnosis, transition and remission between severity levels, and timing of diagnosis and treatment.
Reliability of the Pedar in-shoe system for plantar pressure measurement in diabetic patients with and without neuropathy: a prospective study
Authors: Forogh Bijan , Raissi Gholam Reza , Soleymanzadeh Hosnieh , Bagherzadeh Cham Masumeh 
Published: November 2021

Background:
The aim of this study was to evaluate within and between days’ reliability of the Pedar in-shoe system (Novel GmbH, Munich, Germany) to measure plantar pressure in diabetic patients with and without neuropathy.

Methods:
Forty-seven diabetic patients were divided into diabetic without neuropathy, and with mild, moderate, and severe neuropathy groups based on Toronto Clinical Neuropathy Score. Plantar pressure measurement was taken twice a day to assess within the same day’s reliability and after a mean of 7 days to evaluate between different days’ reliability.

Results:
Intraclass correlation coefficients (ICC) analysis indicated excellent reliability (ICC ≥0.75) in tests within the same day in all groups. Mean pressure and pressure time integral showed excellent levels of ICC reliability in the tests between different days’ in the diabetic group without neuropathy and with mild neuropathy (ICC ≥0.75) and fair-to-excellent in the diabetic group with moderate and severe neuropathy (ICC ≥0.40). Reliability of contact area between different days were excellent in all groups (ICC ≥0.75).

Conclusions:
The results indicated that the Pedar in-shoe system was a reliable measure of plantar pressure within the same day and between different days in diabetic patients with and without neuropathy. The level of reliability was altered with a change of the neuropathy severity.

Level of Evidence:
Level III.
Calcified lumbar disc prolapse technical note and management algorithm: a prospective study
Authors: Ibrahim Fady Michael Fahmy , Khattab Mohamed Fawzy 
Published: November 2021

Background:
The literature lacks sufficient data about management of symptomatic calcified lumbar disc prolapse. The authors introduced a practical algorithm for surgical management of patients after failed conservative measures.

Methods:
A prospective study of 32 patients was conducted between 2012 to 2018. Patients had symptomatic calcified lumbar disc prolapse. Eight patients had unilateral radicular pain, four patients had unilateral claudication pain, nine patients had bilateral claudication pain, and 11 patients had mechanical back pain together with claudication symptoms. Preoperative motor examination revealed one patient with preoperative unilateral foot drop, two patients had preoperative unilateral weak ankle dorsiflexion, and 11 patients had weak extensor halluces longus extension. Fifteen patients had fusion surgery, 11 patients had unilateral decompression, and six patients had bilateral decompression surgery. Functional assessment of patients was done by Oswestry Disability Index (ODI), and radicular pain was assessed by visual analog scale (VAS).

Results:
There were 19 men and 13 women. The mean age was 39.2 yr. The mean operative time for unilateral decompression was 59 min, and bilateral decompression was 80 min. The mean operative time for fusion surgery was 126.4 min. Three patients had intraoperative dural tears. One patient had postoperative ankle dorsiflexion in comparison to preoperative examination, four patients had immediate postoperative lower-limb dysesthesia. The ODI and VAS postoperative improvements were statistically significant when compared with the preoperative values. The mean follow-up was 28.4 mo.

Conclusions:
The results of this study were encouraging in the adoption of the proposed algorithm for management of symptomatic calcified lumbar disc prolapse.

Level of Evidence:
Level III.
Retrospective case series of inverted V-shape tenotomy of gastrocnemius and recession of soleus at the musculotendinous junction for the treatment of fixed equinus deformity in children with cerebral palsy
Authors: Odeh Rabea , Odeh Munzir 
Published: November 2021

Background:
The authors describe results of a surgical percutaneous procedure for gastrocnemius-soleus lengthening at musculotendinous junction using a one-cut inverted V-shape technique for equinus correction in patients with cerebral palsy (CP).

Methods:
This was a retrospective case-series study of 52 patients with spastic CP between November 2001 and November 2016. Gross Motor Function Classification System (GMFCS) levels (II-IV) were involved. Statistical analysis was carried out for ankle dorsiflexion angles with knee extended and flexed, popliteal angle, and Gillette Functional Assessment Questionnaire (FAQ). Failure was determined by recurrence of equinus deformity or developing crouch gait due to overlengthening.

Results:
A mean age of 7 yr was recorded, with a minimum follow-up of 1 yr. A total number of 88 feet were operated upon, including several children who had bilateral deformities. Twelve (23%) patients were operated previously by either percutaneous or open tendo-Achilles lengthening. Success was achieved in 44 patients (85%), and eight patients (15%) had failure. Noncompliance with physical therapy and night splinting were the determined causes of failure for patients who had recurrence. GMFCS level-IV was a particular risk of failure (75%). No patient developed postoperative crouch gait caused by an over-lengthened tendo-Achilles. The improvement in the outcome measures were clinically significant in the successful group.

Conclusions:
The authors’ percutaneous gastrocnemius-soleus lengthening one-cut technique is a safe, cosmetic, and economic day-case surgery. It has low recurrence rate, with minimal risk of developing a crouched gait from overlengthening.

Level of Evidence:
Level IV.
Decreased mRNA expression level of FOXP3 correlate with TNF-α in peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis patients: a case control study
Authors: Patel Sipahee Lal , Prakash Jaya , Gupta Varsha 
Published: November 2021

Background:
Forkhead box P3 (FOXP3), a transcription factor is thought to be the master regulator of regulatory T (Treg) cells in maintaining peripheral tolerance and autoimmunity. The number and functional capabilities have been reported to be low in several diseases including RA, which affects the immune regulatory action of Treg cells. Proinflammatory cytokines such as tumor necrosis factor α (TNF-α), are important in RA pathogenesis, but the influence on Treg cells is poorly understood.

Methods:
In the present study, the messenger RNA (mRNA) expressions of FOXP3 and TNF-α in a group of patients with RA (N=23) and a healthy control group (N=17) were studied in peripheral blood mononuclear cells (PBMCs). PBMCs were chosen as they are practical samples in which changes caused by disease or therapy can be conveniently monitored.

Results:
Expression of FOXP3 was lower (P<0.0001, 0.76 folds) and TNF-α gene expression was higher (P<0.0001, 2.28 folds) in RA patients when compared with the healthy control group. However, a statistically significant correlation could not be established between the FOXP3 and disease activity, but relative mRNA expression of FOXP3 and TNF-α showed a statistically significant correlation (P<0.0283) in RA patients when compared with the healthy control group.

Conclusions:
The results suggested that decreased expression of FOXP3 gene and increased level of TNF-α expression in the presence of rheumatoid factor antibodies (RF) may impair the activity of Treg cells with higher TNF-α levels when compared with patients who were negative for RF.

Level of Evidence:
Level II.
Moderately elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) in patients with no clinical signs or symptoms of infection is not a contraindication for total knee arthroplasty: a retrospective cohort study
Authors: Yeganeh Ali , Amiri Shayan , Moghtadaei Mehdi , Otoukesh Babak , Solati Ahmadreza , Daneshmand Seyedehsan 
Published: November 2021

Background:
It is unclear whether patients with elevated preoperative levels of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) are more prone to periprosthetic joint infection (PJI) after total knee arthroplasty (TKA). The authors aimed to determine how preoperative moderate elevation of ESR or CRP in patients without clinical signs or symptoms of infection is associated with the risk of PJI after TKA surgery.

Methods:
In a prospective study, 315 patients who were elected for unilateral TKA were included, including 237 patients with preoperative normal ESR and CRP, 46 patients with moderate preoperative elevation of ESR (less than 50 mm/hr), and 32 patients with moderate preoperative elevation of CRP (less than 24 mg/dL). Patients with both ESR and CRP elevation were not included in the study. Primary TKA was done using a standard medial parapatellar approach under general anesthesia.

Results:
Overall rate of infection was 0.3% (1 in 320 patients) at a mean follow-up period of 19±5.3 mo. This infection occurred in a patient with normal preoperative ESR and CRP (1 in 237 patients, 0.4%). No infection occurred in 78 patients in either the ESR-elevated or the CRP-elevated group. Accordingly, the rate of infection was not significantly different between the two groups (P=0.83).

Conclusions:
Moderate preoperative elevations of ESR or CRP do not increase the rate of periprosthetic joint infection in patients undergoing total knee arthroplasty.

Level of Evidence:
Level III.
Immunostained Frozen Sections Vs Traditional Permanent Paraffin Sections for Lentigo Maligna Treated With Mohs Micrographic Surgery
Authors: Punchihewa Nisal , Odhavji Sonya , Upjohn Edward , Bekhor Philip 
Published: November 2021

BACKGROUND
Mohs micrographic surgery (MMS) has risen in popularity as a management option for treating lentigo maligna (LM) because of its ability to accurately detect subclinical spread while conserving tissue. The primary concern for opponents of MMS in melanoma remains the difficulty associated with interpretation of frozen sections compared with traditional paraffin sections; this has been made easier with the advent of immunostaining.

OBJECTIVE
Our study aims to assess the concordance in clearance reporting of LM in immunostained frozen sections compared with permanent paraffin sections and hematoxylin and eosin staining.

METHODS
We conducted a retrospective analysis of 38 LM cases treated by MMS between 2017 and 2020 in Melbourne, Australia. Immunostained frozen sections were assessed by a Mohs surgeon, whereas permanent paraffin sections were assessed by an external dermatopathologist.

RESULTS
We report 86% agreement in reporting of LM in immunostained frozen sections compared with permanent paraffin sections. In 5/38 cases, permanent paraffin sections were reported as clear for LM, but the Mohs surgeon had detected positive margins, requiring further excision.

CONCLUSION
For LM treated with MMS, there is a high agreement of clearance reporting between immunostained stained frozen sections and permanent paraffin sections without immunostaining; however, immunostained frozen sections may be more sensitive.
Physical exercise attenuates stress-induced hypertension in rats but not the impairments on the myocardial mechanics
Authors: Silva Ariana A. , Perilhão Mauro S. , Portes Leslie Andrews , Serra Andrey J. , Tucci Paulo Jose Ferreira , Leopoldo André Soares , dos Santos Leonardo , Bocalini Danilo S. 
Published: November 2021

Background:
Acute and chronic stresses have become a health problem in the contemporary society, and prolonged exposure to stressful events are related to the pathogenesis of cardiovascular diseases. Physical exercise is a well-recognized effective nonpharmacological therapy for cardiovascular diseases and stress-induced injuries. Thus, this study evaluated the effect of exercise on the cardiac remodelling of chronically stressed rats.

Methods and results:
Wistar adult rats were used (n = 10 each group) and chronic stress protocol consisted of restricting movement in individual rodent restrainers (60 min, 5 days/week, 12 weeks); and exercise consisted of swimming sessions in a pool (60 min, 5 days/week, 12 weeks). During protocol, blood pressure was measured in conscious rats, and at the end cardiac morphology/function was assessed. Animals exposed to stress exhibited continuous rise in blood pressure from the sixth week, but exercise attenuated it. Similarly, restrained rats increased serum corticosterone compared with nonstressed rats, but exercise also prevented it. No changes were found in cardiac mass, but chronic stress not only impaired the steady state contractions of the cardiac muscle, but also reduced inotropic responses to stretching, increasing calcium and beta-adrenergic receptor stimulation. Despite this, exercise was unable to prevent these functional impairments induced by stress, and instead, the association of stress and physical exercise worsened myocardial compliance.

Conclusion:
Despite the known benefits to the cardiovascular system, our results indicate that aerobic swimming exercise for 12 weeks reduced blood pressure but did not impede the chronic stress-induced myocardial damages in rats.
LPIN1 is a new target gene for essential hypertension
Authors: Fujiwara Akira , Ozawa Moe , Sumida Koichiro , Hirawa Nobuhito , Yatsu Keisuke , Ichihara Nao , Haze Tatsuya , Komiya Shiro , Ohki Yuki , Kobayashi Yusuke , Wakui Hiromichi , Tamura Kouichi 
Published: November 2021

Background:
We previously showed Lipin1 (LPIN1) to be a candidate gene for essential hypertension by genome-wide association studies. LPIN1 encodes the Lipin 1 protein, which contributes to the maintenance of lipid metabolism and glucose homeostasis. However, little is known about the association between LPIN1 and blood pressure (BP).

Methods:
We evaluated the BP of LPIN1-deficient [fatty liver dystrophy (fld)] mice and explored related mechanisms.

Results:
Fld mice have very low expression of LPIN1 and exhibit fatty liver, hypertriglyceridemia, insulin resistance and peripheral neuropathy. Fld mice had significantly elevated SBP and heart rate (HR) throughout the day as measured by a radiotelemetric method. Diurnal variation of SBP and HR was also absent in fld mice. Furthermore, urinary excretion of adrenaline and noradrenaline by fld mice was significantly higher compared with that of control mice. The BP response of fld mice to clonidine (a centrally acting α2-adrenergic receptor agonist) was greater than that of control mice. However, levels of Angiotensinogen and Renin 1 mRNA and urinary nitric oxide excretion were comparable between the two groups. The decrease in SBP at 8 weeks after fat grafting surgery was significantly greater in the transplant group compared with the sham operated group.

Conclusion:
The elevated BP in fld mice may result from activation of the sympathetic nervous system through decreased levels of adipose cytokines. These results indicate that LPIN1 plays a crucial role in blood pressure regulation and that LPIN1 is a new target gene for essential hypertension.