bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Early Subsequent (Revision or Contralateral) ACL Reconstruction: A Retrospective Database Study
Authors: Gallo Matthew C. , Bolia Ioanna K. , Jalali Omid , Rosario Santano , Rounds Alexis , Heidari Keemia Soraya , Trasolini Nicholas A. , Prodromo John P. , Hatch George Frederick , Weber Alexander Evan
Published: February 2020

Background:

Many factors contribute to the risk for subsequent anterior cruciate ligament reconstruction (ACLR) within 2 years from the index procedure.

Purpose/Hypothesis:

The purpose of this study was 2-fold: (1) to evaluate the incidence of subsequent (revision or contralateral) ACLR at 2 years in a large cohort and (2) to explore the association between patient-specific factors and early subsequent ACLR risk by age group. We hypothesize that 2-year subsequent (revision or contralateral) ACLR rates will be low and that risk factors for subsequent (revision or contralateral) ACLR will vary depending on a patient’s age group.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

The California Office of Statewide Health Planning and Development Ambulatory Surgery Database was retrospectively reviewed to assess the incidence of 2-year subsequent (revision or contralateral) ACLR and to identify patient-specific risk factors for early subsequent (revision or contralateral) ACLR by age group between 2005 and 2014.

Results:

Of 94,108 patients included, the rate of subsequent (revision or contralateral) ACLR was highest in patients younger than 21 years (2.4 per 100 person-years; 95% CI, 2.3-2.6) and lowest in those older than 40 years (1.3 per 100 person-years; 95% CI, 1.2-1.4). Younger age, white race (compared with Hispanic in all age groups and Asian in age <21 or >40 years), private insurance if age younger than 21 years, public insurance or worker's compensation claims if age older than 30 years were significantly associated with an increased risk of subsequent (revision or contralateral) ACLR at 2 years.

Conclusion:

Results of the present study provide insight into subsequent (revision or contralateral) ACL reconstruction, which can be used to assess and modify treatment for at-risk patients and highlight the need for data mining to generate clinically applicable research using national and international databases.
Transforming Undergraduate Global Health Education Through a Humanities-Focused Curriculum
Authors: Stewart Kearsley A.
Published: February 2020

Global health needs the humanities today as medicine needed the humanities in the 1970s. When new biomedical technologies threatened to undermine the physician in their primary role of healing the patient, the field of medical humanities emerged to rehumanize the doctor and revive physician empathy through humanities methods and content such as close reading of poetry and novels, reflective writing, and critiquing art. In contrast, many of today’s undergraduate global health students are plagued by a surfeit, rather than a lack, of empathy to “save the world.” As the medical humanities transformed medical education, can today’s humanities and arts, especially the new fields of health humanities and critical medical humanities, transform global health education and practice by igniting a “global health humanities”? This essay focuses on emerging pedagogical and curricular challenges in nonclinical, undergraduate global health training primarily in North America.
Extreme and Inconsistent: A Case-Oriented Regression Analysis of Health, Inequality, and Poverty
Authors: Rambotti Simone , Breiger Ronald L.
Published: February 2020

A methodological paradox characterizes macro-comparative research: it routinely violates the assumptions underlying its dominant method, multiple regression analysis. Comparative researchers have substantive interest in cases, but cases are largely rendered invisible in regression analysis. Researchers seldom recognize the mismatch between the goals of macro-comparative research and the demands of regression methods, and sometimes they end up engaging in strenuous disputes over particular variable effects. A good example is the controversial relationship between income inequality and health. Here, the authors offer an innovative method that combines variable-oriented and case-oriented approaches by turning ordinary least squares regression models “inside out.” The authors estimate case-specific contributions to regression coefficient estimates. They reanalyze data on income inequality, poverty, and life expectancy across 20 affluent countries. Multiple model specifications are dependent primarily on two countries with values on the outcome that are extreme in magnitude and inconsistent with conventional theoretical expectations.
The Impact of Face-to-Face Pharmacist Transitional Care Management Visits on Medication-Related Problems
Authors: Mayzel Bianca , Axtell Sandra , Richardson Carolyn , Link Nicholas
Published: February 2020

Background: Studies are needed to evaluate medication-related problems (MRPs) to assess the effect of a pharmacist on managing medications postdischarge. Objective: To assess the ability of pharmacist-led medication review and reconciliation to reduce the number of MRPs found in transitional care medicine (TCM) visits, leading to medication optimization. Methods: This study involved a retrospective chart review of standard TCM procedure at a family/internal medicine clinic and a prospective, team-based TCM visit in the same clinic. Inclusion criteria included patients discharged from any hospital within our institution and seen in the clinic. The primary outcome was the difference in the proportion of MRPs found between the prospective and retrospective groups. Secondary outcomes included the number and specific type of MRPs found, classified by the Pharmaceutical Care Network Europe tool, and further subdivided by patient aware or unaware of MRP, only in the prospective group, as well as 30-day readmission rate. Results: Patients in the prospective group (n = 50) had an average age of 67.9 years versus 65.5 years in the retrospective group (n = 50). Four times as many patients in the prospective group were found to have MRPs than the retrospective group. The most common MRP was due to a patient-related factor, meaning the cause is related to a patient’s behavior. Patients were unaware of the MRP in a majority of these cases. Thirty-day readmission rate did not differ between the groups. Conclusion: Team-based TCM visits that included a pharmacist-led medication reconciliation uncovered more MRPs than patients who did not have a pharmacist perform a medication reconciliation.
Updated ground motion prediction model for Mexican intermediate-depth intraslab earthquakes including V/H ratios
Authors: Jaimes Miguel A , García-Soto Adrián D
Published: February 2020

This article presents an updated ground motion prediction equation for pseudo acceleration values from Mexican intermediate-depth intraslab earthquakes at rock sites (National Earthquake Hazards Reduction Program (NEHRP) class B) for the horizontal and the vertical components. The equations were built as functions of magnitude, distance to the fault surface of the earthquake and focal depth, using 23 event recordings (366 records). The database is extended from a previous one used to develop a ground motion prediction equation for intraslab earthquakes, including 7 more events and over 80 accelerograms recorded from 2005 to 2017. The previous model neither included the ground motion parameters from the two significant normal-faulting events occurred in 2017, nor the computing of V/ H ratios. Differences in the predicted ground motion parameters are found. Therefore, an updated attenuation model for intraslab earthquakes is developed for distances up to around 400 km and Mw from approximately 5 to 8.2. The model includes a depth-scaling term with focal depths restricted up to 75 km.
RPI-SE: a stacking ensemble learning framework for ncRNA-protein interactions prediction using sequence information
Authors: Yi Hai-Cheng , You Zhu-Hong , Wang Mei-Neng , Guo Zhen-Hao , Wang Yan-Bin , Zhou Ji-Ren
Published: February 2020

Background

The interactions between non-coding RNAs (ncRNA) and proteins play an essential role in many biological processes. Several high-throughput experimental methods have been applied to detect ncRNA-protein interactions. However, these methods are time-consuming and expensive. Accurate and efficient computational methods can assist and accelerate the study of ncRNA-protein interactions.

Results

In this work, we develop a stacking ensemble computational framework, RPI-SE, for effectively predicting ncRNA-protein interactions. More specifically, to fully exploit protein and RNA sequence feature, Position Weight Matrix combined with Legendre Moments is applied to obtain protein evolutionary information. Meanwhile, k-mer sparse matrix is employed to extract efficient feature of ncRNA sequences. Finally, an ensemble learning framework integrated different types of base classifier is developed to predict ncRNA-protein interactions using these discriminative features. The accuracy and robustness of RPI-SE was evaluated on three benchmark data sets under five-fold cross-validation and compared with other state-of-the-art methods.

Conclusions

The results demonstrate that RPI-SE is competent for ncRNA-protein interactions prediction task with high accuracy and robustness. It’s anticipated that this work can provide a computational prediction tool to advance ncRNA-protein interactions related biomedical research.
Acute rupture of a sinus of Valsalva aneurysm into the right atrium: a case report and a narrative review
Authors: Doost Ata , Craig Julie-Ann , Soh Siang Yong
Published: February 2020

Background

Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly which has potential for spontaneous rupture into other cardiac chambers or the pericardial space (depending on its location). A ruptured SVA has a very poor prognosis with high morbidity and mortality. The development of a shunt between the sinus of Valsalva and right-sided cardiac chambers results in a continuous murmur on examination. Our case report is a case of SVA rupture into the right atrium.

Case presentation

In this case report, we describe a 23-year-old patient with an acute onset of chest pain, shortness of breath, palpitations and dizziness starting 2 days prior to presentation to the emergency department. The patient was initially treated for presumed pulmonary embolism overnight while awaiting CTPA the next morning. However, further examination by the inpatient medical team demonstrated a continuous machinery cardiac murmur. Subsequent echocardiography demonstrated an acutely ruptured SVA with shunting to the right atrium. Emergency surgical repair resulted in an excellent outcome for the patient.

Conclusion

A thorough clinical history and physical examination is the cornerstone of all medical encounters. An SVA could be asymptomatic until acute rupture. Echocardiography is the preferred initial diagnostic tool. Additional imaging techniques can be used to confirm the diagnosis. In cases of rupture, prognosis is poor and surgical repair is always required.
Factors associated with high-risk low-level viremia leading to virologic failure: 16-year retrospective study of a Chinese antiretroviral therapy cohort
Authors: Zhang Tong , Ding Haibo , An Minghui , Wang Xiaonan , Tian Wen , Zhao Bin , Han Xiaoxu
Published: February 2020

Background

Low level viremia (LLV) often occurs during antiretroviral therapy (ART) against HIV-1. However, whether LLV increases the risk of virologic failure (VF) is controversial because of the non-uniform definitions of LLV and VF.

Methods

A long-term first line regimen ART cohort from 2002 to 2018 from Shenyang, northeast China, was retrospectively studied. All participants were followed up every 3 to 6 months to evaluate the treatment effect. The high-risk LLV subgroups leading to VF (with strict standards) were explored with Cox proportional hazards model and linear mixed-effect model. The association factors of high-risk LLV were further explored using multivariate logistic regression analyses.

Results

A total of 2155 HIV-1 infected participants were included; of these, 38.7% showed LLV. Both high level LLV (HLLV) and any other level LLV coupled with high level blip (HLB) showed higher risk of VF (hazards ratios, HRHLLV = 5.93, and HRHLB = 2.84, p <  0.05 respectively). Moreover, HR increased with prolonged duration of LLV. Independent factors associated with high-risk LLV included the zenith baseline viral load (VL) above 6 log copies/ml (aOR = 3.49, p = 0.002), nadir baseline CD4 + T cell counts below 200 cells/mm3 (aOR = 1.78, p = 0.011), Manchu (aOR = 2.03, p = 0.003), ART over 60 months (aOR = 1.81, p = 0.004), AZT + 3TC + NVP (aOR = 2.26, p <  0.001) or DDI-based regimen (aOR = 9.96, p = 0.002), and subtype B′ infection (aOR = 8.22, p = 0.001).

Conclusions

In case of VF with strict standards, high-risk LLV leading to VF includes VL above 400 copies/ml, occurring at least once. Serious laboratory indicators or advanced stage of infection, long term ART and subtype B′ infection might also predict the occurrence of high-risk LLV.
Effect of the Xpert MTB/RIF on the detection of pulmonary tuberculosis cases and rifampicin resistance in Shanghai, China
Authors: Wu Zheyuan , Rueda Zulma Vanessa , Li Tao , Zhang Zurong , Jiang Yuan , Sha Wei , Yu Fangyou , Chen Jing , Pan Qichao , Shen Xin , Yuan Zheng’an
Published: February 2020

Background

Xpert MTB/RIF (Xpert) is an automated molecular test recommended by World Health Organization (WHO) for diagnosis of tuberculosis (TB). This study evaluated the effect of Xpert implementation on the detection of pulmonary TB (PTB) and rifampicin-resistant TB (RR-TB) cases in Shanghai, China.

Methods

Xpert was routinely implemented in 2018 for all presumptive PTB patients. All PTB patients above 15 years-old identified within the Provincial TB Control Program during the first half of each of 2017 and 2018, were enrolled to compare the difference in proportions of bacteriological confirmation, patients with drug susceptibility test (DST) results for rifampicin (ie, DST coverage) and RR-TB detection before and after Xpert’s implementation.

Results

A total of 6047 PTB patients were included in the analysis with 1691 tested by Xpert in 2018. Percentages of bacteriological confirmation, DST coverage and RR-TB detection in 2017 and 2018 were 50% vs. 59%, 36% vs. 49% and 2% vs. 3%, respectively (all p-values < 0.05). Among 1103 PTB patients who completed sputum smear, culture and Xpert testing in 2018, Xpert detected an additional 121 (11%) PTB patients who were negative by smear and culture, but missed 248 (23%) smear and/or culture positive patients. Besides, it accounted for an increase of 9% in DST coverage and 1% in RR-TB detection. The median time from first visit to a TB hospital to RR-TB detection was 62 days (interquartile range -IQR 48–84.2) in 2017 vs. 9 days (IQR 2–45.7) in 2018 (p-value < 0.001). In the multivariate model, using Xpert was associated with decreased time to RR-TB detection (adjusted hazard ratio = 4.62, 95% confidence interval: 3.18–6.71).

Conclusions

Integrating Xpert with smear, culture and culture-based DST in a routine setting significantly increased bacteriological confirmation, DST coverage and RR-TB detection with a dramatic reduction in the time to RR-TB diagnosis in Shanghai, China. Our findings can be useful for other regions that attempt to integrate Xpert into routine PTB and RR-TB case-finding cascade. Further study should focus on the identification and elimination of operational level challenges to fully utilize the benefit of rapid diagnosis by Xpert.
Long-term renal graft outcome after parathyroidectomy - a retrospective single centre study
Authors: Patecki Margret , Scheffner Irina , Haller Hermann , Gwinner Wilfried
Published: February 2020

Background

Surgical correction of hyperparathyroidism after kidney transplantation has been associated with significant graft function decline. We examined the effects of parathyroidectomy on short- and long-term graft function and its potential predictors.

Methods

For this retrospective, monocentric study we identified 48 (5.5%) out of 892 patients from our protocol biopsy program who received renal transplantation between 2000 and 2007, with parathyroidectomy after transplantation. Data from up to three years after parathyroidectomy was collected and analyzed with multivariable linear regression analyses.

Results

Main indications for parathyroidectomy were hypercalcemia and graft calcifications. Parathyroidectomy was successful in 47 patients, with a median drop in serum intact parathormone (iPTH) from 394 to 21 pg/ml. Mean estimated glomerular fitration rate (eGFR) before parathyroidectomy was 60 ± 26 ml/min. At three months after parathyroidectomy, the eGFR was 46 ± 18 ml/min (p < 0.001) but remained stable at one and three years (50 ± 20; 49 ± 20 ml/min). The median annual eGFR change was − 0.5 ml/min before and + 1.0 ml/min after parathyroidectomy.

Multivariable modeling identified high iPTH levels and higher eGFR before parathyroidectomy as predictors of the eGFR drop after parathyroidectomy. Lower graft function twelve months after parathyroidectomy was predicted by the eGFR before and the iPTH drop after surgery.

Conclusions

These results indicate that the extent of parathyroidectomy is critical and too much lowering of iPTH should be avoided by timely parathyroidectomy, before reaching extreme high iPTH values. In view of the observed loss of eGFR, parathyroidectomy can be considered safe in patients with an eGFR above 30 ml/min.
An unusual presentation of neuropathic pain following cervical spinal cord injury: a case report
Authors: Chang Min Cheol , Boudier-Revéret Mathieu , Choo Yoo Jin , Hsiao Ming-Yen
Published: February 2020

Background

We report a patient with unusual occipital neuropathic pain (at-level neuropathic pain) due to a small central cervical spinal cord injury (SCI).

Case presentation

A 50-year-old man presented with severe bilateral occipital pain after falling from a height of 2 m, 2 weeks ago. The degree of pain was evaluated to be 9 out of 10 using the numeric rating scale (NRS). The nature of the pain was tingling, burning, and piercing, and hyperalgesia was present over the bilateral posterior head regions. Greater occipital nerve block with bupivacaine and dexamethasone was not effective. On axial T2-cervical magnetic resonance imaging (MRI), a focal high signal change was observed in the central portion of the spinal cord at the C2 level. We deliberated that the patient’s pain was due to the SCI observed on MRI, and after administration of oral medications, the NRS pain score reduced from 9 to 2.

Conclusions

Neuropathic pain caused by SCI varies according to the location and degree of injury of the pain-related neural tracts; therefore, clinicians should closely observe the pain patterns and findings on imaging in patients with SCI to determine the cause of pain accurately.
Muslim women’s experiences of maternity services in the UK: qualitative systematic review and thematic synthesis
Authors: Firdous Tasneema , Darwin Zoe , Hassan Shaima M.
Published: February 2020

Background

This review aimed to identify and synthesise evidence of Muslim women’s experiences of maternity services in the UK. A systematic review and thematic synthesis of qualitative evidence, unrestricted by type of publication was conducted. Muslim women who had accessed maternity services in the UK, regardless of obstetric or medical history were included.

Method

Databases were searched from 2001 to 2019 and screened for inclusion using pre-determined criteria. The Critical Appraisal Skills Programme Qualitative Research Checklist was used to assess study quality and findings were synthesised using thematic synthesis, as described by Thomas and Harden.

Results

Six studies were included. The following five themes were identified: Islamic practices and Individualised care; Talk, Teach and Translate; Injustice, Inequity and Intolerance; If Allah wills; and, ‘It’s not all that bad’. Synthesis highlighted the significance of Islam in shaping many of the women’s decision-making relating to antenatal screening and medication, which was contrasted with healthcare professionals’ limited awareness of the importance of Islam for motherhood. The majority of women experienced poor maternity care which at times indicated stereotypical and discriminatory behaviour.

Conclusions

Education for healthcare professionals is warranted, to enhance the quality and cultural competency in providing appropriate care that acknowledges and meets Muslim women’s needs.
The societal economic burden of autosomal dominant polycystic kidney disease in the United States
Authors: Cloutier Martin , Manceur Ameur M. , Guerin Annie , Aigbogun Myrlene Sanon , Oberdhan Dorothee , Gauthier-Loiselle Marjolaine
Published: February 2020

Background

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited kidney diseases characterized by progressive development of renal cysts and numerous extra-renal manifestations, eventually leading to kidney failure. Given its chronic and progressive nature, ADPKD is expected to carry a substantial economic burden over the course of the disease. However, there is a paucity of evidence on the impact of ADPKD from a societal perspective. This study aimed to estimate the direct and indirect costs associated with ADPKD in the United States (US).

Methods

A prevalence-based approach using data from scientific literature, and governmental and non-governmental organizations was employed to estimate direct healthcare costs (i.e., medical services, prescription drugs), direct non-healthcare costs (i.e., research and advocacy, donors/recipients matching for kidney transplants, transportation to/from dialysis centers), and indirect costs (i.e., patient productivity loss from unemployment, reduced work productivity, and premature mortality, caregivers’ productivity loss and healthcare costs). The incremental costs associated with ADPKD were calculated as the difference between costs incurred over a one-year period by individuals with ADPKD and the US population. Sensitivity analyses using different sources and assumptions were performed to assess robustness of estimates and account for variability in published estimates.

Results

The estimated total annual costs attributed to ADPKD in 2018 ranged from $7.3 to $9.6 billion in sensitivity analyses, equivalent to $51,970 to $68,091 per individual with ADPKD. In the base scenario, direct healthcare costs accounted for $5.7 billion (78.6%) of the total $7.3 billion costs, mostly driven by patients requiring renal replacement therapy ($3.2 billion; 43.3%). Indirect costs accounted for $1.4 billion (19.7%), mostly driven by productivity loss due to unemployment ($784 million; 10.7%) and reduced productivity at work ($390 million; 5.3%). Total excess direct non-healthcare costs were estimated at $125 million (1.7%).

Conclusions

ADPKD carries a considerable economic burden, predominantly attributed to direct healthcare costs, the majority of which are incurred by public and private healthcare payers. Effective and timely interventions to slow down the progression of ADPKD could substantially reduce the economic burden of ADPKD.
Socio-economic impacts of brucellosis on livestock production and reproduction performance in Koibatek and Marigat regions, Baringo County, Kenya
Authors: Lokamar Peter N. , Kutwah Moses A. , Atieli Harrysone , Gumo Sussy , Ouma Collins
Published: February 2020

Background

Brucellosis in Africa is caused by Brucella species transmitted through contaminated or contacts with infected animals or their carcasses. The disease reduces livestock production and reproduction performance evident by frequent episodes of abortion, still births, swollen testes, weak calves/lambs and swollen joints. However, the socio-economic impacts of these brucellosis-associated symptoms on milk, fat, meat and blood production, infertility, sale value, dowry and costs of treatment has not been evaluated extensively in developing countries. In Baringo County, Kenya, there is a continuous movement of cattle as a result of trade and grazing, which predisposes many herds to brucellosis infection. The objective of this study was to investigate the socio-economic impacts of Brucella infection on production systems for sheep, goats, cattle and camels and explore the impact of brucellosis on livestock production and reproduction performance among livestock keeping communities in Baringo County, Kenya. The study adopted a cross-sectional survey using quantitative data collection methods.

Results

Results demonstrated an impact on milk production in suspected brucellosis cases resulting from abortions (OR = 0.151,P < 0.0001) and swollen joints (OR = 2.881,P < 0.0001). In terms of infertility, abortion as a symptom of brucellosis (OR = 0.440,P = 0.002), still birth (OR = 0.628,P = 0.042), and weak calf or lamb (OR = 0.525,P = 0.005) had an impact on infertility. In terms of sale value, abortion (OR = 0.385,P = 0.008), weak calf/lamb (OR = 2.963,P = 0.013) had an impact on sale value. Other analyses demonstrated that for dowry, swollen testes (OR = 5.351,P = 0.032), weak calf and lambs (OR = 0.364,P = 0.019) had a likelihood of reduction of dowry value. Finally, in terms of cost of treatment, abortion (OR = 0.449,P = 0.001), still births (OR = 0.208,P = 0.015), swollen testes (OR = 0.78,P = 0.014), weak calf/lambs (OR = 0.178,P = 0.007) and swollen joints (OR = 0.217,P = 0.003) significantly increased the costs of treatments. There was no impact on fat and meat and blood production.

Conclusion

Even though there was a huge socio-economic impact on milk production, infertility, sale value, and dowry, it was the costs of treatment that was significantly impacted on all symptoms associated with brucellosis on this community. A ‘One Health’ approach in tackling the brucellosis menace as a holistic approach is recommended for both humans and their livestock.
Empagliflozin improved systolic blood pressure, endothelial dysfunction and heart remodeling in the metabolic syndrome ZSF1 rat
Authors: Park Sin-Hee , Farooq Muhammad Akmal , Gaertner Sébastien , Bruckert Christophe , Qureshi Abdul Wahid , Lee Hyun-Ho , Benrahla Djamel , Pollet Brigitte , Stephan Dominique , Ohlmann Patrick , Lessinger Jean-Marc , Mayoux Eric , Auger Cyril , Morel Olivier , Schini-Kerth Valérie B.
Published: February 2020

Background

Empagliflozin (empa), a selective sodium–glucose cotransporter (SGLT)2 inhibitor, reduced cardiovascular mortality and hospitalization for heart failure in patients with type 2 diabetes at high cardiovascular risk independent of glycemic control. The cardiovascular protective effect of empa was evaluated in an experimental model of metabolic syndrome, the obese ZSF1 rat, and its’ lean control.

Methods

Lean and obese ZSF1 rats were either non-treated or treated with empa (30 mg/kg/day) for 6 weeks. Vascular reactivity was assessed using mesenteric artery rings, systolic blood pressure by tail-cuff sphygmomanometry, heart function and structural changes by echocardiography, and protein expression levels by Western blot analysis.

Results

Empa treatment reduced blood glucose levels from 275 to 196 mg/dl in obese ZSF1 rats whereas normoglycemia (134 mg/dl) was present in control lean ZSF1 rats and was unaffected by empa. Obese ZSF1 rats showed increased systolic blood pressure, and blunted endothelium-dependent relaxations associated with the appearance of endothelium-dependent contractile responses (EDCFs) compared to control lean rats. These effects were prevented by the empa treatment. Obese ZSF1 rats showed increased weight of the heart and of the left ventricle volume without the presence of diastolic or systolic dysfunction, which were improved by the empa treatment. An increased expression level of senescence markers (p53, p21, p16), tissue factor, VCAM-1, SGLT1 and SGLT2 and a down-regulation of eNOS were observed in the aortic inner curvature compared to the outer one in the control lean rats, which were prevented by the empa treatment. In the obese ZSF1 rats, no such effects were observed. The empa treatment reduced the increased body weight and weight of lungs, spleen, liver and perirenal fat, hyperglycemia and the increased levels of total cholesterol and triglycerides in obese ZSF1 rats, and increased blood ketone levels and urinary glucose excretion in control lean and obese ZSF1 rats.

Conclusion

Empa reduced glucose levels by 28% and improved both endothelial function and cardiac remodeling in the obese ZSF1 rat. Empa also reduced the increased expression level of senescence, and atherothrombotic markers at arterial sites at risk in the control lean, but not obese, ZSF1 rat.
Metabolic engineering of carbohydrate metabolism systems in Corynebacterium glutamicum for improving the efficiency of l-lysine production from mixed sugar
Authors: Xu Jian-Zhong , Ruan Hao-Zhe , Yu Hai-Bo , Liu Li-Ming , Zhang Weiguo
Published: February 2020

The efficiency of industrial fermentation process mainly depends on carbon yield, final titer and productivity. To improve the efficiency of l-lysine production from mixed sugar, we engineered carbohydrate metabolism systems to enhance the effective use of sugar in this study. A functional metabolic pathway of sucrose and fructose was engineered through introduction of fructokinase from Clostridium acetobutylicum. l-lysine production was further increased through replacement of phosphoenolpyruvate-dependent glucose and fructose uptake system (PTSGlc and PTSFru) by inositol permeases (IolT1 and IolT2) and ATP-dependent glucokinase (ATP-GlK). However, the shortage of intracellular ATP has a significantly negative impact on sugar consumption rate, cell growth and l-lysine production. To overcome this defect, the recombinant strain was modified to co-express bifunctional ADP-dependent glucokinase (ADP-GlK/PFK) and NADH dehydrogenase (NDH-2) as well as to inactivate SigmaH factor (SigH), thus reducing the consumption of ATP and increasing ATP regeneration. Combination of these genetic modifications resulted in an engineered C. glutamicum strain K-8 capable of producing 221.3 ± 17.6 g/L l-lysine with productivity of 5.53 g/L/h and carbon yield of 0.71 g/g glucose in fed-batch fermentation. As far as we know, this is the best efficiency of l-lysine production from mixed sugar. This is also the first report for improving the efficiency of l-lysine production by systematic modification of carbohydrate metabolism systems.
Antibacterial activity of iron oxide, iron nitride, and tobramycin conjugated nanoparticles against Pseudomonas aeruginosa biofilms
Authors: Armijo Leisha M. , Wawrzyniec Stephen J. , Kopciuch Michael , Brandt Yekaterina I. , Rivera Antonio C. , Withers Nathan J. , Cook Nathaniel C. , Huber Dale L. , Monson Todd C. , Smyth Hugh D. C. , Osiński Marek
Published: February 2020

Background

Novel methods are necessary to reduce morbidity and mortality of patients suffering from infections withPseudomonas aeruginosa. Being the most common infectious species of thePseudomonasgenus,P. aeruginosais the primary Gram-negative etiology responsible for nosocomial infections. Due to the ubiquity and high adaptability of this species, an effective universal treatment method forP. aeruginosainfection still eludes investigators, despite the extensive research in this area.

Results

We report bacterial inhibition by iron-oxide (nominally magnetite) nanoparticles (NPs) alone, having a mean hydrodynamic diameter of ~ 16 nm, as well as alginate-capped iron-oxide NPs. Alginate capping increased the average hydrodynamic diameter to ~ 230 nm. We also investigated alginate-capped iron-oxide NP-drug conjugates, with a practically unchanged hydrodynamic diameter of ~ 232 nm. Susceptibility and minimum inhibitory concentration (MIC) of the NPs, NP-tobramycin conjugates, and tobramycin alone were determined in the PAO1 bacterial colonies. Investigations into susceptibility using the disk diffusion method were done after 3 days of biofilm growth and after 60 days of growth. MIC of all compounds of interest was determined after 60-days of growth, to ensure thorough establishment of biofilm colonies.

Conclusions

Positive inhibition is reported for uncapped and alginate-capped iron-oxide NPs, and the corresponding MICs are presented. We report zero susceptibility to iron-oxide NPs capped with polyethylene glycol, suggesting that the capping agent plays a major role in enabling bactericidal ability in of the nanocomposite. Our findings suggest that the alginate-coated nanocomposites investigated in this study have the potential to overcome the bacterial biofilm barrier. Magnetic field application increases the action, likely via enhanced diffusion of the iron-oxide NPs and NP-drug conjugates through mucin and alginate barriers, which are characteristic of cystic-fibrosis respiratory infections. We demonstrate that iron-oxide NPs coated with alginate, as well as alginate-coated magnetite–tobramycin conjugates inhibitP. aeruginosagrowth and biofilm formation in established colonies. We have also determined that susceptibility to tobramycin decreases for longer culture times. However, susceptibility to the iron-oxide NP compounds did not demonstrate any comparable decrease with increasing culture time. These findings imply that iron-oxide NPs are promising lower-cost alternatives to silver NPs in antibacterial coatings, solutions, and drugs, as well as other applications in which microbial abolition or infestation prevention is sought.
Examining the factorial validity of the Quality of Life Scale
Authors: Reeves Ashley J. , Baker Russell T. , Casanova Madeline P. , Cheatham Scott W. , Pickering Michael A.
Published: February 2020

Background

Quality of life (QoL) is important to assess in patient care. Researchers have previously claimed validity of the Quality of Life Scale (QOLS) across multiple samples of individuals, but close inspection of results suggest further psychometric investigation of the instrument is warranted. Therefore, the purposes of this study were to: 1) evaluate the proposed five-factor, 15-item and three-factor, 16-item QOLS; 2) if the factor structure could not be confirmed, re-assess the QOLS using exploratory factor analysis (EFA) and covariance modeling to identify a parsimonious refinement of the QOLS structure for future investigation.

Methods

Participants varying in age, physical activity level, and identified medical condition(s) were recruited from clinical sites and ResearchMatch. Confirmatory factor analyses (CFA) were performed on the full sample (n = 1036) based on proposed 15- and 16-item QOLS versions. Subsequent EFA and covariance modeling was performed on a random subset of the data (n1 = 518) to identify a more parsimonious version of the QOLS. The psychometric properties of the newly proposed model were confirmed in the remaining half of participants (n2 = 518). Further examination of the scale psychometric properties was completed using invariance testing procedures across sex and health status sub-categories.

Results

Neither the 15- nor 16-item QOLS CFA met model fit recommendations. Subsequent EFA and covariance modeling analyses revealed a one-factor, five-item scale that satisfied contemporary statistical and model fit standards. Follow-up CFA confirmed the revised model structure; however, invariance testing requirements across sex and injury status subgroups were not met.

Conclusions

Neither the 15- nor 16-item QOLS exhibited psychometric attributes that support construct validity. Our analyses indicate a new, short-form model, might offer a more appropriate and parsimonious scale from some of the original QOLS items; however, invariance testing across sex and injury status suggested the psychometric properties still vary between sub-groups. Given the scale design concerns and the results of this study, developing a new instrument, or identifying a different, better validated instrument to assess QoL in research and practice is recommended.
Levels of sex steroid hormones and their receptors in women with preeclampsia
Authors: Lan Kuo-Chung , Lai Yun-Ju , Cheng Hsin-Hsin , Tsai Ni-Chin , Su Yu-Ting , Tsai Ching-Chang , Hsu Te-Yao
Published: February 2020

Background

Pregnant women have high serum concentrations of sex steroid hormones, which are major regulators of paracrine and autocrine responses for many maternal and placental functions. The main purpose of this study was to compare patients with preeclampsia and patients with uncomplicated pregnancies in terms of serum steroid hormones (estradiol [E2], progesterone [P4], dehydroepiandrosterone sulfate [DHEAS], and testosterone [T]) throughout pregnancy and the levels of cord blood and placental steroid receptors during the third trimester.

Methods

Quantitative real-time reverse transcription PCR, western blotting, and immunohistochemistry were used to determine the levels of steroid hormones in the serum and cord blood and the placental levels of estrogen receptor-α (ERα), ERβ, androgen receptor (AR), and progesterone receptor (PR).

Results

There were 45 women in the uncomplicated pregnancy group and 30 women in the preeclampsia group. Serum levels of T were greater and serum levels of E2 were reduced in the preeclampsia group, but the two groups had similar levels of P4 and DHEAS during the third trimester. Cord blood had a decreased level of DHEAS in the preeclampsia group, but the two groups had similar levels of P4, E2, and T. The two groups had similar placental mRNA levels of ERα, ERβ, AR, and PR, but the preeclampsia group had a higher level of ERβ protein and a lower level of ERα protein. Immunohistochemistry indicated that the preeclampsia group had a greater level of ERβ in the nucleus and cytoplasm of syncytiotrophoblasts and stromal cells.

Conclusions

Women with preeclampsia had lower levels of steroid hormones, estrogen, and ERα but higher levels of T and ERβ. These molecules may have roles in the pathogenesis of preeclampsia.
Retraction Note to: Stromal vascular fraction cells for the treatment of critical limb ischemia: a pilot study
Authors: Darinskas Adas , Paskevicius Mindaugas , Apanavicius Gintaras , Vilkevicius Gintaris , Labanauskas Liutauras , Ichim Thomas E. , Rimdeika Rytis
Published: February 2020

The Editor-in-Chief and the publisher have retracted this article [1]. An investigation by the Lithuanian Bioethics Committee concluded that, contrary to the statements in the article, the study described was not conducted in the Vilnius City Clinical Hospital and the Commission of Medical Ethics did not issue any approval for such a study.
Compliance of private pharmacies in Uganda with controlled prescription drugs regulations: a mixed-methods study
Authors: Kamba Pakoyo Fadhiru , Mulangwa John , Kaggwa Bruhan , Kitutu Freddy Eric , Sewankambo Nelson Kaulukusi , Katabira Elly Tebasoboke , Byakika-Kibwika Pauline , Adome Richard Odoi , Bollinger Robert Cyril
Published: February 2020

Background

Controlled prescription drug use disorders are a growing global health challenge in Sub-Saharan Africa. Effective supply chain regulations on dispensing and stock control are important for controlling this epidemic. Since compliance with these regulations in resource-limited countries is poor, there is need to understand its predictors in order to reduce the risk of prescription drug use disorders.

Methods

A mixed-methods study utilizing a structured questionnaire and a simulated client guide was undertaken in Kampala and Mbale towns in Uganda. The questionnaire recorded self-reported dispensing and verified stock control practices and their covariates from 101 private pharmacies. The guide recorded actual dispensing practices from 27 pharmacies. Snowball sampling was done to enrich the sample with pharmacies that stock opioids. The mean compliance with good dispensing and stock control practices was calculated. Multivariate logistic regression analyses were applied to identify predictors of compliance.

Results

The mean compliance with dispensing and stock control requirements was 82.9% and 23%, respectively. Twenty percent and 40% of the pharmacies dispensed pethidine without a prescription and with invalid prescriptions, respectively. Having a pharmacist on duty (OR = 5.17; p = 0.02), prior in-service training on narcotics regulations (OR = 3.51; p = 0.04), and previous narcotics audits by the regulator (OR = 5.11; p = 0.01) were independent predictors of compliance with stock control requirements. Pharmacies with a previous history of poor compliance with dispensing requirements were less likely to demonstrate good compliance (OR = 0.21; p = 0.01).

Conclusions

There is suboptimal compliance to controlled prescription drug regulations among Uganda’s pharmacies. A previous history of poor compliance to dispensing requirements predicted low compliance in subsequent assessments. Training and regulatory audits increased compliance in stock control but not dispensing. Expansion of training and audits to more pharmacies and/or incentives for compliance are necessary.
Biceps tenotomy versus tenodesis: patient-reported outcomes and satisfaction
Authors: Aflatooni Justin O. , Meeks Brett D. , Froehle Andrew W. , Bonner Kevin F.
Published: February 2020

Background

Biceps tenotomy and tenodesis are surgical treatments for pathology of the proximal tendon of the long head of the biceps. There is debate over which procedure provides better patient outcomes.

Purpose

Compare patient-reported outcomes and satisfaction between biceps tenotomy and tenodesis.

Methods

This retrospective cohort study including all patients undergoing arthroscopic biceps tenodesis or tenotomy as part of more extensive shoulder surgery with a single surgeon. Concomitant procedures included rotator cuff repair, subacromial decompression, acromioclavicular joint resection, and debridement. Patients 36–81 years old were contacted by phone at > 2-year post-operatively to complete a biceps-specific outcome questionnaire. Subject decision not to participate was the sole exclusion criterion. Satisfaction scores and frequencies of potential biceps-related downsides (biceps cramping/spasms, biceps pain, shoulder pain, weakness, cosmetic deformity) were analyzed for the effects of procedure, sex, and age.

Results

Satisfaction score distributions were similar between patients with tenodesis and patients with tenotomy (χ2 = 8.34, P = 0.08), although slightly more patients with tenodesis than patients with tenotomy reported being satisfied or very satisfied (96% versus 91%). Perceived downsides occurred more frequently among patients with tenotomy than in patients with tenodesis: 59% of patients with tenotomy reported ≥ 1 downside, versus 37% of patients with tenodesis (P < 0.01). In patients reporting ≥ 1 downside, distributions of total downsides differed between procedures (χ2 = 10.04, P = 0.04): patients with tenotomy were more likely to report multiple concurrent downsides than were patients with tenodesis (31% versus 16%). Each individual downside tended to be reported as present by a greater proportion of patients with tenotomy than patients with tenodesis. Sex had no effect on satisfaction or downsides, but there was a trend for older patients to report higher satisfaction and fewer downsides.

Conclusions

Biceps tenotomy and tenodesis are both viable treatments for proximal biceps tendon pathology, yielding high patient satisfaction. There were trends toward greater satisfaction and fewer problems in patients with tenodesis. Still, younger patients with tenodesis did report perceived downsides. Alternatively, older patients tended to be more satisfied with both procedures overall. Regardless of procedure, most patients receiving either tenotomy or tenodesis would undergo their respective surgery again.

Level of Evidence

Level III evidence, retrospective comparative cohort study
Tripartite signalling by NMDA receptors
Authors: Rajani Vishaal , Sengar Ameet S. , Salter Michael W.
Published: February 2020

N-methyl-d-aspartate receptors (NMDARs) are excitatory glutamatergic receptors that are fundamental for many neuronal processes, including synaptic plasticity. NMDARs are comprised of four subunits derived from heterogeneous subunit families, yielding a complex diversity in NMDAR form and function. The quadruply-liganded state of binding of two glutamate and two glycine molecules to the receptor drives channel gating, allowing for monovalent cation flux, Ca2+ entry and the initiation of Ca2+-dependent signalling. In addition to this ionotropic function, non-ionotropic signalling can be initiated through the exclusive binding of glycine or of glutamate to the NMDAR. This binding may trigger a transmembrane conformational change of the receptor, inducing intracellular protein-protein signalling between the cytoplasmic domain and secondary messengers. In this review, we outline signalling cascades that can be activated by NMDARs and propose that the receptor transduces signalling through three parallel streams: (i) signalling via both glycine and glutamate binding, (ii) signalling via glycine binding, and (iii) signalling via glutamate binding. This variety in signal transduction mechanisms and downstream signalling cascades complements the widespread prevalence and rich diversity of NMDAR activity throughout the central nervous system and in disease pathology.
Early trajectories of skin thickening are associated with severity and mortality in systemic sclerosis
Authors:   the French National Scleroderma Cohort Network, Ledoult Emmanuel , Launay David , Béhal Hélène , Mouthon Luc , Pugnet Grégory , Lega Jean-Christophe , Agard Christian , Allanore Yannick , Jego Patrick , Fauchais Anne-Laure , Harlé Jean-Robert , Berthier Sabine , Aouba Achille , Mekinian Arsène , Diot Elisabeth , Truchetet Marie-Elise , Boulon Carine , Duhamel Alain , Hachulla Eric , Sobanski Vincent
Published: February 2020

Background

Systemic sclerosis (SSc) is a severe and highly heterogeneous disease. The modified Rodnan skin score (mRSS) is a widely used tool for the assessment of the extent and degree of skin thickness. This study aimed to identify the classes of patients with early similar skin thickening trajectories without any a priori assumptions and study their associations with organ involvement and survival.

Methods

From the French SSc national cohort, patients with a disease duration of less than 2 years at inclusion and with at least 2 mRSS available within the first 4 years of follow-up were enrolled. Classes of patients with similar mRSS trajectories were identified based on a latent class mixed model. The clinical characteristics and survival rate were compared between the obtained classes.

Results

A total of 198 patients fulfilled the inclusion criteria, with a total of 641 mRSS available. The median disease duration and follow-up were 0.8 (interquartile range 0.4; 1.2) and 6.3 (3.8; 8.9) years, respectively. Individual trajectories of mRSS were highly heterogeneous between patients. Models with 1–6 latent classes of trajectories were sequentially assessed, and the 5-class model represented the best fit to data. Each class was characterized by a unique global trajectory of mRSS. The median disease duration did not differ significantly between classes. Baseline organ involvement was more frequent in classes with significant change over time (classes 2–5) than in class 1 (low baseline mRSS without significant change over time). Using Cox regression, we observed a progressively increasing risk of death from classes 1 to 5.

Conclusions

Early identification of clinical phenotype based on skin thickening trajectories could predict morbi-mortality in SSc. This study suggested that mRSS trajectories characterization might be pivotal for clinical practice and future trial designs.