bluuebunny/crossref_metadata_2025 huggingface dataset:
Boswellic Acid Synergizes With Low-Level Ionizing Radiation to Modulate Bisphenol Induced-Lung Toxicity in Rats by Inhibiting JNK/ERK/c-Fos Pathway
Authors: Mansour Somya Z. , Moawed Fatma S. M. , Badawy Monda M. M. , Mohamed Hebatallah E.
Published: October 2020

Bisphenol A (BPA) is a low molecular weight chemical compound that has a deleterious effect on the endocrine system. It was used in plastics manufacturing with injurious effects on different body systems. Occupational exposure to low-level ionizing radiation (<1 Gy) is shown to attenuate an established inflammatory process and therefore enhance cell protection. Therefore, the objective of this study was to investigate the protective effect of boswellic acid (BA) accompanied by whole-body low-dose gamma radiation (γ-R) against BPA-induced lung toxicity in male albino rats. BPA intoxication induced with 500 mg/kg BW. Rats received 50 mg BA/kg BW by gastric gavage concomitant with 0.5 Gy γ-R over 4 weeks. The immunoblotting and biochemical results revealed that BA and/or γ-R inhibited BPA-induced lung toxicity by reducing oxidative damage biomolecules; (MDA and NADPH oxidase gene expression), inflammatory indices (MPO, TNF-α, IL-6, and gene expression of CXCR-4). Moreover, BA and or/γ-R ameliorated the lung inflammation via regulation of the JNK/ERK/c-Fos and Nrf2/ HO-1 signaling pathways. Interestingly, our data demonstrated that BA in synergistic interaction with γ-R is efficacious control against BPA-induced lung injury via anti-oxidant mediated anti-inflammatory activities.
Bullseye: Effects of autonomy support and enhanced expectancies on dart throwing
Authors: Wehlmann Julian Alexander , Wulf Gabriele
Published: October 2020

The present study examined the combined influence of two motivational key factors in the OPTIMAL theory of motor learning, 1 enhanced expectancies (EE) and autonomy support (AS), on the learning of a dart-throwing task. In one group (AS/EE), participants were provided with a success criterion that could be met relatively easily (EE) and two small choices (AS). A control group practiced under neutral conditions. On Day 1, participants completed a pretest and six 12-trial blocks of practice from a 2 m distance to the bullseye. Two days later, retention and transfer (novel distance of 2.37 m) tests were conducted. Self-efficacy was assessed throughout the practice phase and before the retention test. The results showed that the AS/EE group had higher self-efficacy during practice and demonstrated greater dart-throwing accuracy on the retention and transfer tests compared with the control group. The findings have implications for practical settings: They show that providing learners with a liberal definition of success and minor choices can be sufficient to enhance motor skill learning.
Tocilizumab drug levels during pregnancy and lactation: A woman who discontinued tocilizumab therapy until the end of the first trimester and resumed it after birth
Authors: Saito Jumpei , Yakuwa Naho , Kaneko Kayoko , Goto Mikako , Kawasaki Hiroyo , Hamamachi Yurie , Suzuki Tomo , Sago Haruhiko , Yamatani Akimasa , Murashima Atsuko
Published: October 2020

The demand for tocilizumab is increasing in women who wish to bear children and who have active rheumatoid arthritis. Described here is a woman with rheumatoid arthritis who discontinued her tocilizumab therapy at the end of the first trimester and resumed it after delivery and where tocilizumab levels in maternal serum, infant serum, and the breast milk were measured. Tocilizumab was not detected in maternal serum just before delivery, or in umbilical cord blood or infant serum after birth. Tocilizumab levels in colostrum after intravenous injection were 0.57% of those in serum. Tocilizumab treatment in the first trimester was not associated with a significant drug level in the fetus at delivery and no fetal complications were noted .
Short-Term Morbidity and Predictors of Adverse Events Following Esthesioneuroblastoma Surgery
Authors: Goshtasbi Khodayar , Birkenbeuel Jack L. , Abouzari Mehdi , Lehrich Brandon M. , Yasaka Tyler M. , Abiri Arash , Muhonen Ethan G. , Hsu Frank P. K. , Kuan Edward C.
Published: October 2020

Introduction

The short-term adverse events and predictors of morbidity in surgical resection of esthesioneuroblastoma (ENB) are largely unknown, and investigating these variables can help direct planning for at-risk patients.

Methods

The 2005–2017 National Surgical Quality Improvement Program database was queried to identify patients with a diagnosis of ENB undergoing skull base surgery for tumor resection. Information regarding demographics, patient morbidity score, pre-operative and intra-operative data, and post-operative outcomes were extracted. Cox proportional hazard analysis was utilized to assess complication and readmission/reoperation rates.

Results

A total of 95 patients undergoing skull base surgery for resection of ENB were included. Mean age, BMI, operation time, and post-operative length of stay (LOS) of the cohort were 53.6 ± 16.2 years, 29.1 ± 6.5, 392.0 ± 204.6 minutes, and 5.8 ± 4.6 days, respectively. In total, 31 patients (32.6%) experienced at least one 30-day adverse event, which included blood transfusion intra-operatively or within 72 hours from the operation (22.1%), readmission (10.7%), intubation >48 hours (7.4%), reintubation (4.2%), organ or space infection (4.2%), reoperation (4.0%), superficial or deep surgical site infection (2.1%), sepsis (2.1%), pulmonary embolism (1.1%), and myocardial infarction (1.1%). Patients who experienced at least one adverse event had significantly higher operation time (486.8 ± 230.4 vs. 347.5 ± 176.2 minutes, p = 0.002), LOS (9.2 ± 5.6 days vs. 4.2 ± 3.0, p < 0.001), and lower hematocrit (37.3 ± 5.9 vs. 41.2 ± 3.8, p < 0.001) and albumin levels (3.8 ± 0.6 vs. 4.2 ± 0.3, p = 0.009). Patients with a higher American Society of Anesthesiologists (ASA) score (HR = 2.39; p = 0.047) or longer operation time (HR = 1.004; p = 0.001) had a significantly higher risk for experiencing adverse events. Obesity was not associated with different intra- or post-operative outcomes, but older patients had shorter operations ( p = 0.002) and LOS ( p = 0.0014).

Conclusion

Longer operation time and lower pre-operative hematocrit and albumin levels may all increase complication rates in ENB resection. Patients with high ASA score or more advanced age may have different short-term outcomes.
Desmoplastic Fibroma of the Mandible: Case Report and Review of Literature
Authors: Shekhar M Guna , Reddy R Sudhakara , Ravikanth Manyam , Lavanya Reddy , Kumar Manikya
Published: October 2020

Desmoplastic fibroma is a rare benign and locally aggressive myofibroblastic tumour, frequently seen in the second or third decades of life. The mandible and the maxilla are infrequently involved, and the mandible is the most commonly affected of the facial bones. Nevertheless, reports of desmoplastic fibroma affecting the mandible are scarce in the literature. This article reports a rare case of desmoplastic fibroma affecting the angle of the mandible in a 10-year-old Indian male. In addition, a review of literature relating to desmoplastic fibroma affecting the angle of the mandible is presented.
Making the Grade? Modification of Dental Radiograph Quality Ratings
Authors: Rodgers George D , Sharif Mohammad O , Smith Adam B , Kellett Margaret , Brunton Paul A
Published: October 2020

Aims

To compare the intra- and inter-assessor agreement and operator preference of a modified (four-grade) quality rating system for dental radiographs with the current National Radiological Protection Board (NRPB) (three-grade) quality rating system.

Methods

Sixty radiographic images of varying quality were selected by retrospective review of dental records from a general dental practice. The images were sorted into groups to represent examples of radiographic quality (1=excellent, 2=diagnostically acceptable, 3=diagnostically compromised, 4=unacceptable). A ‘gold standard’ for radiological quality assessment was provided by a consultant in dental and maxillofacial radiology. A compact disc (CD) of the 60 images was produced and posted to a panel of 14 general dental practitioners (GDPs) who were asked to grade the quality of the images using two different systems on two occasions separated by a washout period of two days. The practitioners graded the radiographs using the currently accepted method for assessing radiographic quality (the three-grade NRPB system) and the alternative four-grade system. The quality of the images on the CD was deemed appropriate by the consultant.

Results

The strength of inter-assessor agreement was weaker when using a four-grade system in comparison to a three-grade system, reducing to a mean of κ=0.51 from a mean of κ=0.61 when using the original grading system. Mean agreement did not fall below ‘moderate agreement’ (κ=0.41–0.60). Eleven of the 14 GDPs preferred the four-grade system.

Conclusion

The GDPs who participated in this study preferred the four-grade system to the three-grade system when comparing the quality of dental radiographs. However, the strength of agreement was weaker when using the four-grade system in comparison to the three-grade system. Overall, the results are equivocal. However, they should help to inform specialist dental radiology panels, should revision of quality grading be undertaken in the future.
Evolution of the rat hind limb transplant as an experimental model of vascularized composite allotransplantation: Approaches and advantages
Authors: Fleissig Yoram Y , Beare Jason E , LeBlanc Amanda J , Kaufman Christina L
Published: October 2020

As clinical experience with surgical techniques and immunosuppression in vascularized composite allotransplantation recipients has accumulated, vascularized composite allotransplantation for hand and face have become standard of care in some countries for select patients who have experienced catastrophic tissue loss. Experience to date suggests that clinical vascularized composite allotransplantation grafts undergo the same processes of allograft rejection as solid organ grafts. Nonetheless, there are some distinct differences, especially with respect to the immunologic influence of the skin and how the graft is affected by environmental and traumatic insults. Understanding the mechanisms around these similarities and differences has the potential to not only improve vascularized composite allotransplantation outcomes but also outcomes for all types of transplants and to contribute to our understanding of how complex systems of immunity and function work together. A distinct disadvantage in the study of upper extremity vascularized composite allotransplantation recipients is the low number of clinical transplants performed each year. As upper extremity transplantation is a quality of life rather than a lifesaving transplant, these numbers are not likely to increase significantly until the risks of systemic immunosuppression can be reduced. As such, experimental models of vascularized composite allotransplantation are essential to test hypotheses regarding unique characteristics of graft rejection and acceptance of vascularized composite allotransplantation allografts. Rat hind limb vascularized composite allotransplantation models have been widely used to address these questions and provide essential proof-of-concept findings which can then be extended to other experimental models, including mice and large animal models, as new concepts are translated to the clinic. Here, we review the large body of rat hind limb vascularized composite allotransplantation models in the literature, with a focus on the various surgical models that have been developed, contrasting the characteristics of the specific model and how they have been applied. We hope that this review will assist other researchers in choosing the most appropriate rat hind limb transplantation model for their scientific interests.
Vaping in today’s pandemic: E-cigarette, or vaping, product use–associated lung injury mimicking COVID-19 in teenagers presenting with respiratory distress
Authors: Darmawan Daphne O , Gwal Kriti , Goudy Brian D , Jhawar Sanjay , Nandalike Kiran
Published: October 2020

The clinical presentation of children and adolescents infected with severe acute respiratory syndrome coronavirus 2 can range from asymptomatic to mild or moderate manifestations. We present a case series of three adolescents who presented during the coronavirus disease 2019 (COVID-19) pandemic with symptoms concerning for COVID-19, including fever, abdominal symptoms, cough, respiratory distress, and hypoxemia. Their laboratory results showed elevated inflammatory markers that are also commonly seen in COVID-19. The chest imaging studies mimicked COVID-19 with non-specific ground glass opacities and interstitial prominence patterns. However, severe acute respiratory syndrome coronavirus 2 testing was negative and further questioning of these adolescents and their parents revealed a history of vaping marijuana-related products leading to the eventual diagnosis of e-cigarette, or vaping, product use–associated lung injury. Our patients were successfully treated with corticosteroids. The providers caring for pediatric patients, especially adolescents, should continue to have a high index of suspicion for e-cigarette, or vaping, product use–associated lung injury in patients presenting with unexplained respiratory failure, while ruling out COVID-19.
In memory of professor Sirkka-Liisa Ekman
Authors: Norberg Astrid , Mazaheri Monir
Published: October 2020

Sirkka-Liisa Ekman, Professor Emeritus of Nursing at Karolinska Institutet, passed away on 3 September 2020 at the age of 77, surrounded by her immediate family. She was a giant in geriatric care and dementia care.
Treatment of lavage drainage under spinal endoscopy on lumbar spinal tuberculosis with vertebral lesions
Authors: Zhang Xun , Wang Keran , Xia Yu , Gao Xiang , Du Yu , Chen Liang
Published: October 2020

To investigate the efficacy and safety of the treatment of percutaneous endoscopic debridement (PED) and continuous lavage drainage (CLD) on lumbar tuberculosis. Total 31 patients diagnosed with lumbar tuberculosis, who underwent the PED and CLD from January 2012 to January 2018 in our hospital were included. The operation time, intraoperative blood loss, complications were analyzed. The recovery of local tuberculosis was evaluated by erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and visual analogue scale (VAS) before and after operation. The patients were followed up for 18 to 84 months. At the last follow-up, lumbar lordosis (LL), the Japanese Orthopaedic Association (JOA) score and imaging data were used to evaluate the recovery of spinal structure and function. There were no complications for all patients. During the follow-up of 3 to 12 months after operation, ESR and CRP returned to normal. The VAS score of local pain was significantly lower than that before operation ( p < 0.05). The LL and JOA scores of the patients at the last follow-up were significantly better than those before operation ( p < 0.05), and the lumbar CT and MR suggested the healing of vertebral lesions.

PED and CLD might be an effective surgical treatment for spinal tuberculosis.
The Prognostic Value of Metabolic Profiling in Older Patients With a Proximal Femoral Fracture
Authors: van der Sijp Max P.L. , Suchiman H. Eka D. , Eijk Monica , Vojinovic Dina , Niggebrugge Arthur H. P. , Blauw Gerard J. , Achterberg Wilco P. , Slagboom P. Eline
Published: October 2020

Introduction:

High mortality rates of approximately 20% within 1 year after treatment are observed for patients with proximal femoral fractures. This preliminary study explores the prognostic value of a previously constructed mortality risk score based on a set of 14 metabolites for the survival and functional recovery in patients with proximal femoral fractures.

Materials and Methods:

A prospective observational cohort study was conducted including patients admitted with a proximal femoral fracture. The primary outcome was patient survival, and the recovery of independence in activities of daily living was included as a secondary outcome. The mortality risk score was constructed for each patient and its prognostic value was tested for the whole population.

Results:

Data was available form 136 patients. The mean age of all patients was 82.1 years, with a median follow-up of 6 months. Within this period, 19.0% of all patients died and 51.1% recovered to their prefracture level of independence. The mortality score was significantly associated with mortality (HR, 2.74; 95% CI, 1.61-4.66; P < 0.001), but showed only a fair prediction accuracy (AUC = 0.68) and a borderline significant comparison of the mortality score tertile groups in survival analyses (P = 0.049). No decisive associations were found in any of the analyses for the functional recovery of patients.

Discussion:

These findings support the previously determined prognostic value of the mortality risk score. However, the independent prognostic value when adjusted for potential confounding factors is yet to be assessed. Also, a risk score constructed for this specific patient population might achieve higher accuracies for the prediction of survival and functional recovery.

Conclusions:

A modest prediction accuracy was observed for the mortality risk score in this population. More elaborate studies are needed to validate these findings and develop a tailored model for clinical purposes in this patient population.
Do Pediatric Patients With Anterior Cruciate Ligament Tears Have a Higher Rate of Familial Anterior Cruciate Ligament Injury?
Authors: Bram Joshua T. , Pascual-Leone Nicolas , Patel Neeraj M. , DeFrancesco Christopher J. , Talathi Nakul S. , Ganley Theodore J.
Published: October 2020

Background:

Several studies have examined the anterior cruciate ligament (ACL) injury history among relatives of patients undergoing ACL reconstruction (ACLR), but they have primarily analyzed adults with variable results.

Hypothesis:

We hypothesized that he rate of familial ACL injuries among pediatric patients with ACL tears would be greater than that among pediatric patients with uninjured knees.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Pediatric patients (≤18 years of age) who underwent ACLR between January 2009 and May 2016 were contacted to complete a questionnaire on subsequent complications and family history of ACL tears. A control cohort was recruited from children with uninjured knees seen in the concussion clinic of our institution. Binary logistic regression was used to determine the factors predictive of having a familial ACL tear history or complications.

Results:

Overall, 450 pediatric patients with primary ACL tears were included. Age at the time of surgery was 14.9 ± 2.2 years with a follow-up of 4.3 ± 2.1 years. When compared with 267 control patients, those with an ACL tear reported a higher rate of first-degree relatives with an ACL injury history (25.1% vs 12.0%; P < .001). In multivariate analysis, children with ACL injury had nearly 3 times (odds ratio [OR], 2.7) higher odds of having a first-degree relative with an ACL tear (95% CI, 1.7-4.2; P < .001). Patients were stratified by the number of first-degree relatives with ACL tears: no relatives, 1 relative, or ≥2 relatives. Children with ≥2 first-degree relatives were more likely to sustain a postoperative graft failure (OR, 5.1; 95% CI 1.7-15.2; P = .003) or a complication requiring surgical intervention (OR, 7.5; 95% CI, 2.6-22.0; P < .001).

Conclusion:

A family history of ACL injury is more likely in pediatric patients with ACL tears than in uninjured children. Further, patients undergoing primary ACLR as well as a strong family history of ACL tears are more likely to sustain a postoperative graft rupture or complication requiring surgery.
Psychological and Neurophysiological Effects of Robot Assisted Activity in Elderly People With Cognitive Decline
Authors: Goda Akio , Shimura Takaki , Murata Shin , Kodama Takayuki , Nakano Hideki , Ohsugi Hironori
Published: October 2020

Robot-assisted activity (RAA) is a non-pharmacological therapy used to treat behavioral and psychological symptoms of dementia. This study investigated the immediate effects of RAA on psychological and neurophysiological indices. Twenty-eight elderly people were assigned to the cognitive decline group ( n = 11) or control group ( n = 17) based on their Mini-Mental State Examination scores. After 5-min RAA sessions that involved patients interacting with a communication robot, patient emotions and mood states were measured, and resting-state EEG activity and salivary cortisol were assessed before and after RAA. We found that compared with those in the control group, participants in the cognitive decline group did not enjoy RAA using the communication robot. This was corroborated by EEG findings indicating decreased relaxation immediately after RAA exposure. These results suggested that participants with cognitive decline had difficulty understanding the contents of communication with the robot. Our results indicated that elderly people who have cognitive decline and use day-service centers are less likely to experience the immediate benefits of RAA, including positive emotions and mental relaxation. To conduct effective RAA for such populations, it may be useful to select a method that is better understood and enjoyed by participants.
Impossible Theorem and Possibilities of Development Studies
Authors: Nayak Bhabani Shankar
Published: October 2020

This article evaluates the ‘impossibility theorem’ of ‘development studies’. It is imperative to reject the ‘impossibility theorem’ based on essentialist perspectives and performative indicators of economic growth and development. It is necessary to revive the radical promise of ‘development studies’ as a discipline to address the issues and predicaments of people and their societies around the world. A simple rejection of the ‘impossibility theorem’ is not possible unless ‘development studies’ reasserts itself as a critical discipline to analyse, understand and guide social, economic and cultural transformations based on historical experiences. The article argues that ‘development studies’ have to be free from the influences of economics and its model-driven logic and revive its emancipatory language of transformation in our society.
Small-Gauge Pars Plana Vitrectomy for Visually Significant Vitreous Floaters
Authors: Fink Samantha , Kumar Jaya B. , Cunningham Matthew A.
Published: October 2020

Purpose:

This article evaluates our experience at a retina-only private practice with small-gauge pars plana vitrectomy (PPV) for visually significant vitreous floaters. We review the surgical outcomes, complication rates, and percentage of second-eye surgery for the same indication.

Methods:

A retrospective, interventional case series was conducted of consecutive patients undergoing PPV for significant vitreous floaters from September 2014 to December 2018 at a high-volume vitreoretinal surgery practice. Preoperative visual acuity (VA), complication rates, and visual outcome following surgery were evaluated.

Results:

A total of 104 eyes in 81 patients underwent PPV for visually significant floaters; 35 (43.2%) patients had PPV in both eyes. Mean preoperative VA was 0.16 ± 0.17 logMAR (∼20/29 Snellen equivalent) and improved to 0.12 ± 0.15 logMAR (∼20/26 Snellen; Wilcoxon test, P = .008) at the last follow-up after PPV. All patients had improvement in VA at the final postoperative visit, with a VA of 20/40 or better achieved in 93.3% of cases. The complication rate of vitreous hemorrhage postoperatively was 0.96%. There were no cases of postoperative retinal tears, breaks, or endophthalmitis.

Conclusions:

Small-gauge PPV in the carefully selected patient is an effective and safe procedure to eliminate symptoms. VA following PPV for vitreous floaters significantly improved. Nearly half of the patients studied (43.2%) underwent PPV in the other eye.
Conservative management of a fourth ventricular epidermoid in a patient with Gardner syndrome
Authors: Heller Gordon D.
Published: October 2020

Gardner Syndrome is a rare disease with clinical manifestations of familial intestinal polyposis with osteomas. Cutaneous and subcutaneous lesions are common and epidermoid cyst is a characteristic dermatologic finding. This case report presents a novel finding of an intracranial epidermoid situated in the fourth ventricle in a patient with Gardner Syndrome. This intracranial epidermoid has been followed with sequential magnetic resonance imaging (MRI) for 10 years with progressive growth of the lesion. This suggests the conservative management is an option in patients with an enlarging epidermoid cyst in the fourth ventricle.

Plain language summary

Non-operative treatment of a cyst in the brain in a syndrome called Gardner syndrome. What is Gardner syndrome? Gardner syndrome is a rare disease and form of familial adenomatous polyposis (FAP) that is characterized by multiple small growths of cells (polyps) in the colon and various types of tumors, both noncancerous (benign) and cancerous (malignant). It is caused by changes (mutations) in the APC gene. Abnormal changes on the skin and under the skin are common as well as growths called epidermoid cysts. The cysts develop when cells that are meant to become skin, hair, and nails (epithelial cells) are trapped among the cells that form the brain. Epidermoid brain cysts may be diagnosed by magnetic resonance imaging (MRI) and computerized tomography (CT) scans. Typical treatment usually involves surgery. What was the aim of this case report? To present a different management strategy for patients with Gardner Syndrome with epidermoid brain cysts. How was this patient treated? This patient is the first patient with Gardner Syndrome with a very rare epidermoid brain cyst reported to be treated in a conservative manner. The patient was monitored for 10 years with regular MRI scans and the cyst continued to grow over this time. Despite this growth the patient has shown no signs of a buildup of fluid in the cavities deep within the brain (called hydrocephalus). The patient experienced nonfocal headaches, which were relieved with medication so doctors decided not to surgically remove the cyst. Why is this case important? Conservative management of epidermoid brain cysts in Gardner patients has not been reported before. This case report shows that conservative management may be an alternative option for patients with a growing epidermoid cyst in the fourth ventricle of the brain. Conservative treatment is designed to avoid invasive treatments or surgery and provides a different option for patients who are unable to have surgery.
Flow analysis of conical spiral mandrel dies
Authors: Bouzari N , Goharpey F
Published: October 2020

Spiral dies are divided into three categories, namely: Flat Spiral Die (FSD), Cylindrical Spiral Mandrel Die (SMD), and Conical Spiral Mandrel Die (CSD). These dies are used to produce films via blown film extrusion and multilayer films via co-extrusion. The goal is to improve the flow distribution and to decrease the pressure drop which will result in uniform film thickness and reduced energy dissipation. A viscous power-law fluid model shows that low-pressure drop and proper flow distribution can be achieved in a CSD simultaneously. As the number of grooves and the initial channel depth increases, the flow distribution becomes more uniform and the pressure drop decreases. Also, there is an optimum initial clearance and clearance increment angle. The model results show that the pseudo-plastic fluid has more appropriate performance than the Newtonian and dilatant fluids in improving the flow distribution and reducing the pressure drop.
GTS-21, an α7nAChR agonist, increases pulmonary bacterial clearance in mice by restoring hyperoxia-compromised macrophage function
Authors: Sitapara Ravikumar A. , Gauthier Alex G. , Patel Vivek S. , Lin Mosi , Zur Michelle , Ashby Charles R. , Mantell Lin L.
Published: October 2020

Background

Mechanical ventilation, in combination with supraphysiological concentrations of oxygen (i.e., hyperoxia), is routinely used to treat patients with respiratory distress, such as COVID-19. However, prolonged exposure to hyperoxia compromises the clearance of invading pathogens by impairing macrophage phagocytosis. Previously, we have shown that the exposure of mice to hyperoxia induces the release of the nuclear protein high mobility group box-1 (HMGB1) into the pulmonary airways. Furthermore, extracellular HMGB1 impairs macrophage phagocytosis and increases the mortality of mice infected withPseudomonas aeruginosa(PA). The aim of this study was to determine whether GTS-21 (3-(2,4-dimethoxybenzylidene) anabaseine), an α7 nicotinic acetylcholine receptor (α7nAChR) agonist, could (1) inhibit hyperoxia-induced HMGB1 release into the airways; (2) enhance macrophage phagocytosis and (3) increase bacterial clearance from the lungs in a mouse model of ventilator-associated pneumonia.

Method

GTS-21 (0.04, 0.4, and 4 mg/kg) or saline were administered by intraperitoneal injection to mice that were exposed to hyperoxia (≥ 99% O2) and subsequently challenged with PA.

Results

The systemic administration of 4 mg/kg i.p. of GTS-21 significantly increased bacterial clearance, decreased acute lung injury and decreased accumulation of airway HMGB1 compared to the saline control. To determine the mechanism of action of GTS-21, RAW 264.7 cells, a macrophage-like cell line, were incubated with different concentrations of GTS-21 in the presence of 95% O2. The phagocytic activity of macrophages was significantly increased by GTS-21 in a dose-dependent manner. In addition, GTS-21 significantly inhibited the cytoplasmic translocation and release of HMGB1 from RAW 264.7 cells and attenuated hyperoxia-induced NF-κB activation in macrophages and mouse lungs exposed to hyperoxia and infected with PA.

Conclusions

Our results indicate that GTS-21 is efficacious in improving bacterial clearance and reducing acute lung injury via enhancing macrophage function by inhibiting the release of nuclear HMGB1. Therefore, the α7nAChR represents a possible pharmacological target to improve the clinical outcome of patients on ventilators by augmenting host defense against bacterial infections.
Effect of family doctor contract services on patient perceived quality of primary care in southern China
Authors: Feng Shanshan , Cheng Aiyun , Luo Zhenni , Xiao Yao , Zhang Luwen
Published: October 2020

Background

Family doctor contract service is an important service item in China’s primary care reform. This research was designed to evaluate the impact of the provision of family doctor contract services on the patient-perceived quality of primary care, and therefore give evidence-based policy suggestions.

Methods

This cross-sectional study of family doctor contract service policy was conducted in three pilot cities in the Pearl River Delta, South China, using a multistage stratified sampling method. The validated Primary Care Assessment Tool-Adult Edition (PCAT-AS) was used to measure the quality of primary care services. PCAT-AS assesses each of the unique characteristics of primary care including first contact, continuity, comprehensiveness, coordination, family-centeredness, community orientation, culture orientation. Data was collected through face-to-face interviews held from July to November, 2015. Covariate analysis and multivariate Linear Regression were adopted to explore the effect of contract on the quality of primary care by controlling for the socio-demographic status and health care service utilization factors.

Results

A total of 828 valid questionnaires were collected. Among the interviewees, 453 patients signed the contract (54.7%) and 375 did not (45.3%). Multivariate linear regression showed that contracted patients reported higher scores in dimensions of PCAT total score (β = − 8.98,P < 0.000), first contact-utilization(β = − 0.71,P < 0.001), first contact-accessibility(β = − 1.49,P < 0.001), continuity (β = 1.27,P < 0.001), coordination (referral) (β = − 1.42,P < 0.001), comprehensiveness (utilization) (β = − 1.70,P < 0.001), comprehensiveness (provision) (β = − 0.99,P < 0.001),family-centeredness(β = − 0.52,P < 0.01), community orientation(β = − 1.78,P < 0.001), than un- contracted after controlling socio-demographic and service utilization factors. There were no statistically significant differences in the dimensions of coordination (information system) (β = − 0.25,P = 0.137) and culture orientation (β = − 0.264,P = 0.056) between the two both groups.

Conclusions

This study demonstrates that the pilot implementation of family doctor contract services has significantly improved patients’ perceived primary care quality in the pilot cities, and could help solve the quality problem of primary care. It needs further promotion across the province.
New strategies of physical activity assessment in cystic fibrosis: a pilot study
Authors: Savi Daniela , Graziano Luigi , Giordani Barbara , Schiavetto Stefano , Vito Corrado De , Migliara Giuseppe , Simmonds Nicholas J. , Palange Paolo , Elborn J. Stuart
Published: October 2020

Background

Regular physical activity (PA) is a valued part of cystic fibrosis (CF) care. Although the accelerometer, SenseWear Armband (SWA), accurately measures habitual PA in CF, it is mostly used for research purposes. For the first time, we analyzed different methods of measuring PA in daily life by the use of smartphones and other electronic devices such as smartwatch and Fitbit.

Methods

Twenty-four stable adults with CF (mean age 37.5 ± 11.5SD yrs.; FEV158 ± 19% predicted, BMI 22.9 ± 3.2) were studied. Daily PA was monitored for seven consecutive days. All patients wore the accelerometer SWA and at the same time they monitored PA with the electronic device they used routinely. They were allocated into one of four arms according to their device: Smartwatch, Fitbit, Android smartphones and iOS smartphones. PA related measurements included: duration of PA, energy expenditure, number of steps.

Results

There was a good agreement between SWA and Fitbit for number of steps (p = 0.605) and energy expenditure (p = 0.143). iOS smartphones were similar to SWA in monitoring the number of steps (p = 0.911). Significant differences were found between SWA and both Smartwatch and Android smartphones.

Conclusions

Fitbit and iOS smartphones seem to be a valuable approach to monitor daily PA. They provide a good performance to measure step number compared to SWA.
A retrospective case series of Fournier’s gangrene: necrotizing fasciitis in perineum and perianal region
Authors: Zhang Nan , Yu Xin , Zhang Kai , Liu Tongjun
Published: October 2020

Background

To describe the clinical characteristics and management for Fournier’s gangrene. Experience summary and literature references are provided for future treatment improvement.

Methods

We retrospectively reviewed the cases diagnosed with Fournier’s gangrene in our department from June 2016 to June 2019. Clinical data, including manifestation, diagnosis, treatment and outcomes for Fournier’s gangrene were presented.

Results

There were 12 patients enrolled in this paper, with the average age of 60 years old. It showed a male predominance with male-to-female ratio of 6:1. The average of laboratory risk indicator for necrotizing fasciitis (LRINEC) score was 10.1. Diabetes mellitus was the main predisposing disease. 11 patients received emergency debridement and 1 patient died of sepsis on the 2nd day after admission. The mortality rate was 8.3%. 6 cases developed complications, including sepsis, pneumonia, renal and heart failure. Negative pressure wound therapy (NPWT) was applied in 10 cases, while the rest 1 received normal daily dressing changes because of fecal contamination. Flaps were utilized in 2 patients to cover the defect, including one with advancement flap and one with pudendal-thigh flap, while others received secondary suture, secondary healing, skin graft or combined management. No relapse was observed during the follow-up visits.

Conclusions

Fournier’s gangrene is a life-threatening infection that requires early diagnosis and surgery intervention. The predisposing disease, clinical manifestation and LRINEC score should be taken into comprehensive consideration, which is helpful for timely diagnosis. Moreover, further successful treatment depends on the aggressive debridement, broad-spectrum antibiotics therapy, wound management and closure choice.
Severe vivax malaria trends in the last two years: a study from a tertiary care centre, Delhi, India
Authors: Matlani Monika , Kojom Loick P. , Mishra Neelangi , Dogra Vinita , Singh Vineeta
Published: October 2020

Background

Plasmodium vivax, once considered benign species, is recently being recognised to be causing severe malaria like Plasmodium falciparum. In the present study, the authors report the trends in malaria severity in P. vivax among patients from a Delhi government hospital. The aim of the study was to understand the disease severity and the burden of severe vivax malaria.

Methods

A hospital based study was carried out from June 2017 to December 2018 at a tertiary care centre from Delhi, India. Patients were tested for malaria using peripheral blood smear (PBS) and/or rapid malaria antigen test (RMAT). The severe and non-severe vivax malaria categorization was done as per the WHO guidelines. Sociodemographic, clinic and paraclinical data were collected from patients and their medical records.

Results

Of the 205 patients, 177 (86.3%) had P. vivax infection, 22 (10.7%) had P. falciparum infection and six (2.9%) had mixed infection with both the species. Out of 177 P. vivax cases included in this study one or more manifestations of severe malaria was found in 58 cases (32.7%). Severe anaemia (56.9%), jaundice (15%) and significant bleeding (15%) were the most common complications reported in most of patients, along with thrombocytopenia.

Conclusions

In this study, it is evident that vivax malaria is emerging as the new severe disease in malaria patients, a significant shift in the paradigm of P. vivax pathogenesis. The spectrum of complications and alterations in the laboratory parameters in P. vivax clinical cases also indicate the recent shift in the disease severity.
The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors
Authors: Jin Ying , Chen Dong-Liang , Wang Feng , Yang Chao-pin , Chen Xu-Xian , You Jin-qi , Huang Jin-Sheng , Shao Yang , Zhu Dong-Qin , Ouyang Yu-Ming , Luo Hui-Yan , Wang Zhi-Qiang , Wang Feng-Hua , Li Yu-Hong , Xu Rui-Hua , Zhang Dong-Sheng
Published: October 2020

A more common and noninvasive predicting biomarker for programmed cell death 1 (PD-1) antibody remains to be explored. We assessed 46 patients with advanced gastric cancer who received PD-1 antibody immunotherapy and 425-genes next-generation sequencing (NGS) testing. Patients who had a > 25% decline in maximal somatic variant allelic frequency (maxVAF) had a longer progression free survival (PFS) and higher response rate than those who did not (7.3 months vs 3.6 months, p = 0.0011; 53.3% vs 13.3%, p = 0.06). The median PFS of patients with undetectable and detectable post-treatment circulating tumor DNA (ctDNA) was 7.4 months vs. 4.9 months (p = 0.025). Mutation status of TGFBR2, RHOA, and PREX2 in baseline ctDNA influenced the PFS of immunotherapy (p < 0.05). Patients with alterations in CEBPA, FGFR4, MET or KMT2B (p = 0.09) gene had greater likelihood of immune-related adverse events (irAEs). ctDNA can serve as a potential biomarker of the response to immunotherapy in advanced gastric cancers, and its potential role in predicting irAEs worth further exploration.
Long non-coding RNAs (lncRNAs) in spermatogenesis and male infertility
Authors: Joshi Meghali , Rajender Singh
Published: October 2020

Background

Long non-coding RNAs (lncRNAs) have a size of more than 200 bp and are known to regulate a host of crucial cellular processes like proliferation, differentiation and apoptosis by regulating gene expression. While small noncoding RNAs (ncRNAs) such as miRNAs, siRNAs, Piwi-interacting RNAs have been extensively studied in male germ cell development, the role of lncRNAs in spermatogenesis remains largely unknown.

Objective

In this article, we have reviewed the biology and role of lncRNAs in spermatogenesis along with the tools available for data analysis.

Results and conclusions

Till date, three microarray and four RNA-seq studies have been undertaken to identify lncRNAs in mouse testes or germ cells. These studies were done on pre-natal, post-natal, adult testis, and different germ cells to identify lncRNAs regulating spermatogenesis. In case of humans, five RNA-seq studies on different germ cell populations, including two on sperm, were undertaken. We compared three studies on human germ cells to identify common lncRNAs and found 15 lncRNAs (LINC00635, LINC00521, LINC00174, LINC00654, LINC00710, LINC00226, LINC00326, LINC00494, LINC00535, LINC00616, LINC00662, LINC00668, LINC00467, LINC00608, and LINC00658) to show consistent differential expression across these studies. Some of the targets of these lncRNAs included CENPB, FAM98B, GOLGA6 family, RPGR, TPM2, GNB5, KCNQ10T1, TAZ, LIN28A, CDKN2B, CDKN2A, CDKN1A, CDKN1B, CDKN1C, EZH2, SUZ12, VEGFA genes. A lone study on human male infertility identified 9879 differentially expressed lncRNAs with three (lnc32058, lnc09522, and lnc98497) of them showing specific and high expression in immotile sperm in comparison to normal motile sperm. A few lncRNAs (Mrhl, Drm, Spga-lncRNAs, NLC1-C, HongrES2, Tsx, LncRNA-tcam1, Tug1, Tesra, AK015322, Gm2044, and LncRNA033862) have been functionally validated for their roles in spermatogenesis. Apart from rodents and humans, studies on sheep and bull have also identified lncRNAs potentially important for spermatogenesis. A number of these non-coding RNAs are strong candidates for further research on their roles in spermatogenesis.
A research agenda for non-communicable disease prevention and control in India
Authors: Kataria Ishu , Siddiqui Mariam , Gillespie Theresa , Goodman Michael , Dhillon Preet K. , Bann Carla , Squiers Linda
Published: October 2020

Background

Non-communicable diseases contribute to 62% of total deaths in India; of concern are the preventable premature deaths, which account for a staggering 48% of mortality. The objective of this study was to establish a consensus research agenda for non-communicable disease prevention and control that has the potential to impact polices, programmes and healthcare delivery in India.

Methods

To develop a non-communicable disease research agenda, we engaged our community collaborative board and scientific advisory group in a three-step process using two web-based surveys and one in-person meeting. First, the Delphi methodology was used to generate topics. Second, these ideas were deliberated upon during the in-person meeting, leading to the prioritisation of 23 research questions, which were subjected to Strength, Weakness, Opportunities and Threat analysis by the stakeholders using the Snow Card methodology with the scientific advisory group and community collaborative board. This step resulted in the identification of 15 low effort, high impact priority research questions for various health outcomes across research disciplines based on discussion with the larger group to reach consensus. Finally, the second web-based survey resulted in the identification of 15 key priority research questions by all stakeholders as being the most important using a linear mixed effect regression model.

Results

The final set of 15 priority research questions focused on interventions at the individual, community, systems and policy levels. Research questions focused on identifying interventions that strengthen healthcare systems and healthcare delivery, including models of care and improved access to non-communicable disease screening, diagnosis and treatment, determining the impact of government policies, assessing the effectiveness of prevention programmes (e.g. tobacco, environmental improvements), and testing research tools and resources to monitor non-communicable diseases at the population level.

Conclusion

To produce the evidence base for selecting and implementing non-communicable disease programmes and policies in India, investments are needed. These investments should be guided by a national research agenda for the prevention and control of non-communicable diseases in India. Our findings could form the backbone of a national research agenda for non-communicable diseases in India that could be refined and then adopted by government agencies, the private sector, non-governmental and community-based organisations.
Systemic dendrimer-drug nanomedicines for long-term treatment of mild-moderate cerebral palsy in a rabbit model
Authors: Zhang Zhi , Lin Yi-An , Kim Soo-Young , Su Lilly , Liu Jinhuan , Kannan Rangaramanujam M. , Kannan Sujatha
Published: October 2020

Background

Neuroinflammation mediated by microglia plays a central role in the pathogenesis of perinatal/neonatal brain injury, including cerebral palsy (CP). Therapeutics mitigating neuroinflammation potentially provide an effective strategy to slow the disease progression and rescue normal brain development. Building on our prior results which showed that a generation-4 hydroxyl poly(amidoamine) (PAMAM) dendrimer could deliver drugs specifically to activated glia from systemic circulation, we evaluated the sustained efficacy of a generation-6 (G6) hydroxyl-terminated PAMAM dendrimer that showed a longer blood circulation time and increased brain accumulation. N-acetyl-l-cysteine (NAC), an antioxidant and anti-inflammatory agent that has high plasma protein binding properties and poor brain penetration, was conjugated to G6-PAMAM dendrimer-NAC (G6D-NAC). The efficacy of microglia-targeted G6D-NAC conjugate was evaluated in a clinically relevant rabbit model of CP, with a mild/moderate CP phenotype to provide a longer survival of untreated CP kits, enabling the assessment of sustained efficacy over 15 days of life.

Methods

G6D-NAC was conjugated and characterized. Cytotoxicity and anti-inflammatory assays were performed in BV-2 microglial cells. The efficacy of G6D-NAC was evaluated in a rabbit model of CP. CP kits were randomly divided into 5 groups on postnatal day 1 (PND1) and received an intravenous injection of a single dose of PBS, or G6D-NAC (2 or 5 mg/kg), or NAC (2 or 5 mg/kg). Neurobehavioral tests, microglia morphology, and neuroinflammation were evaluated at postnatal day 5 (PND5) and day 15 (PND15).

Results

A single dose of systemic ‘long circulating’ G6D-NAC showed a significant penetration across the impaired blood-brain-barrier (BBB), delivered NAC specifically to activated microglia, and significantly reduced microglia-mediated neuroinflammation in both the cortex and cerebellum white matter areas. Moreover, G6D-NAC treatment significantly improved neonatal rabbit survival rate and rescued motor function to nearly healthy control levels at least up to 15 days after birth (PND15), while CP kits treated with free NAC died before PND9.

Conclusions

Targeted delivery of therapeutics to activated microglia in neonatal brain injury can ameliorate pro-inflammatory microglial responses to injury, promote survival rate, and improve neurological outcomes that can be sustained for a long period. Appropriate manipulation of activated microglia enabled by G6D-NAC can impact the injury significantly beyond inflammation.