bluuebunny/crossref_metadata_2025 huggingface dataset:
Musculoskeletal ultrasonography combined with electromyography in the diagnosis of massage-inducted lateral plantar nerve injury
Authors: Jiang Zhende , Zhang Hanyang , Yu Tong , Du Yanhui , Qian Zhihui , Chang Fei
Published: July 2020

Introduction:

It is well known that foot massage is a very prevalent stress relief method in China. Literatures have reported various massage-inducted peripheral nerve injuries. However, massage-inducted lateral plantar nerve (LPN) injury is very rare. Here, we represent an unusual case of massage-inducted LPN damage, and we also report the diagnostic method of this patient using musculoskeletal ultrasonography combined with electromyography (EMG).

Patient concerns:

A 21-year-old woman presented symptoms of redness, swelling, pain and numbness in the medial right ankle joint for 2 days.

Diagnosis:

The results of musculoskeletal ultrasonography and EMG provide great help for doctors to make accurate diagnosis. The patient was eventually diagnosed with LPN injury.

Interventions:

No further foot massage was allowed. Vitamin B12 was taken orally for 2 months. Conservative therapy, including electrical stimulation therapy and infrared therapy, was conducted. Besides, active rehabilitation training was also performed.

Outcomes:

The discomfort symptoms were relieved significantly after 2 months conservative treatment. Clinical symptoms and EMG examination illustrated satisfactory result during follow up time.

Conclusion:

The report showed that the masseur should be very careful when doing foot massage to prevent nerve damage. Besides, musculoskeletal ultrasonography combined with EMG can provide important evidence for accurate and effective diagnosis of LPN injury.
Diagnostic significance of cytomegalovirus DNA quantitation in gastrointestinal biopsies: comparison with histopathological data and blood cytomegalovirus DNA
Authors: Alacam Sema , Karabulut Nuran , Bakir Ayfer , Onel Mustafa , Buyuk Melek , Gulluoglu Mine , Agacfidan Ali
Published: July 2020

Objectives

This study aims to improve the diagnosis of gastrointestinal (GI) cytomegalovirus (CMV) disease. It presents the results of a novel study in which CMV blood viral load (BVL), tissue viral load (TVL) determined by PCR and hematoxylin-eosin (HE)/immunohistochemistry (IHC) results of GI biopsies are examined comparatively.

Methods

CMV DNA was investigated by quantitative real-time PCR in blood and GI biopsy specimens of 76 patients suspected of CMV disease. Biopsies were also performed HE/IHC stainings in the pathology laboratory.

Results

This study included 76 patients whose median age was 34.5 years and 58% (44) were male. Tissue CMV PCR positivity was detected in the highest colon (40/53;75.5%) samples. HE, IHC, blood and tissue CMV PCR positivity rates of all samples were 15.8, 25, 50 and 71.1%, respectively. When IHC was used as the gold standard test for ROC analysis, the optimal cutoff values for the maximum sensitivity and specificity for BVL and TVL were 1.91 log10 copies/ml and 3.82 log10 copies/mg, respectively. Sensitivity and specificity for the cutoff value of tissue CMV DNA were 78.9 and 74.3%, respectively (P < 0.001).

Conclusion

In this study, CMV DNA was detected in 71.1% of the tissue samples of the cases by PCR. Since the sensitivity of the histopathological examinations accepted as the gold standard is low, simultaneous with the histopathological examinations, determination of BVL, TVL and the identification of optimal cutoff values have been shown to support the diagnosis of GI CMV disease.
Hepatitis C and hepatitis C-related advanced liver disease hospitalisation trends before and after the Strategic Plan for Tackling Hepatitis C in the National Health System
Authors: Garrido-Estepa Macarena , Latasa Pello , Flores-Herrera Javier , García Comas Luis
Published: July 2020

Introduction

This work evaluates the burden and trends of hepatitis C virus (HCV)-associated hospitalisations in Spain before and after the implementation of the Strategic Plan for Tackling Hepatitis C in the National Health System in 2015.

Methods

HCV-related hospitalisation discharges from 2005 to 2017 were obtained from the National Registry of Hospitalisations. A descriptive analysis of the hospitalisations was performed.

Results

From 2005 to 2017, there were 674 067 HCV-related hospitalisations: 1.2%, 29.9%, 63.9% and 5% of them due to acute, carriers, chronic and unspecified hepatitis C. Average age of the patients was 57.7 years (SD: 16.4), average hospital stay was 9.1 days (SD: 12.2) and intra-hospital case-fatality rate was 6.5%. Hospitalisation rates decreased notably (P < 0.05) in 2016–2017 compared to 2005–2015 for all [hospitalisation rate ratio (HRR): 0.77], males (HRR: 0.80), females (HRR: 0.74), chronic hepatitis C (HRR: 0.84), non-advanced liver disease (N-AdLD) (HRR: 0.80) and AdLD (HRR: 0.73). Acute HCV (HRR: 0.54) and carriers (HRR: 0.49) show decreases in 2016–2017 vs. 2005–2015, although their rates started to decrease in 2008/2009. Unspecified HCV hospitalisation rates increased (P < 0.05) in 2016–2017 (HRR: 2.02) vs. 2005–2015. From 2015 to 2017, cost per patient increased from 5981 euros to 6349 euros, but overall cost decreased, as hospitalisations rates decreased from 302 to 264 million euros.

Discussion

HCV-related hospitalisation rates decreased notably in 2016 and 2017 after the strategic plan for tackling hepatitis C was launched. Although cost per AdLD patient increased in 2016 and 2017, globally costs were reduced around 35 million euros per year.
Outcomes of loco-regional anaesthesia in ureteroscopy for stone disease: a systematic review
Authors: Schembri Matthew , Agarwal Vineet , Pietropaolo Amelia , Somani Bhaskar
Published: July 2020

Purpose of review

Routine ureteroscopy (URS) for stone disease is performed under a general anaesthesia. However, controversy exists on the role of loco-regional anaesthesia and the outcomes associated with it. Here we review the challenges, outcomes and complications of loco-regional anaesthesia for URS. A Cochrane style review was performed in accordance with the preferred reporting items for systematic reviews and meta-analyses guidelines to evaluate the outcomes of loco-reginal anaesthesia for URS in stone disease, including all English language articles from January 1980 and December 2019.

Recent findings

Twenty-one studies (1843 procedures) with a mean age of 46 years and a male : female ratio of 1.2 : 1 underwent URS under loco-regional anaesthesia. The mean stone size was 9 mm (range:4–21 mm) and except five papers, all other papers included stones in the ureter of which the majority were in the distal ureter. The conversion to general anaesthesia was needed in 2.7% patients (range 1–21%) across studies, with a stone free rate of 48–100%. The complication rate varied from 1.4 to 36%. Although the intraoperative complications included ureteric injury (n = 21) or perforation (n = 4), the postoperative complications included fever (n = 37), urinary tract infection (n = 20), haematuria (n = 4), urosepsis (n = 4) and others (n = 7).

The present systematic review shows that local anaesthetic URS is a potential alternative to general anaesthetic URS in carefully selected patients. Randomised controlled trials with subgroup analysis are required to further assess whether loco-regional anaesthesia URS is noninferior to general anaesthesia URS and might help determine if the former approach should become more widespread.
Synergistic effect of Zataria multiflora and Lavandula stoechas essential oils on phenotype detection of efflux pump against multidrug-resistant Acinetobacter baumannii isolates
Authors: Agahi Parisa , Mahdavi-Ourtakand Masoumeh , Noorbakhsh Fatemeh
Published: July 2020

Background:

Acinetobacter baumannii infections have become a major cause of hospital-acquired infections worldwide and can rapidly develop resistance to antibiotics. There are various mechanisms for multidrug resistance in the A. baumannii and efflux pumps is the most important among those. The purpose of this study is to evaluate the synergistic effect of Zataria multiflora and Lavandula stoechas essential oils on phenotype detection of efflux pump against multidrug-resistant A. baumannii isolates.

Methods:

A total of 55 A. baumannii strains were collected from clinical specimens and those with multidrug resistant (MDR) has been isolated by using the Kirby-Bauer disk diffusion method. Z. multiflora and L. stoechas essential oils were extracted and analyzed by gas chromatography–mass spectrometry. The minimum inhibitory concentration for antimicrobial activity of essential oils against MDR A. baumannii strains and fractional inhibitory concentration index was evaluated to determine their synergistic effect. The activity of efflux pumps of MDR strains was investigated by the ethidium bromide-agar cartwheel method and the inhibitory effect of essential oils on the efflux pumps activity was evaluated.

Results:

The results of this study showed that Z. multiflora and L. stoechas essential oils had additive antibacterial effects against MDR A. baumannii strains. The study of efflux pumps by cartwheel method showed that 10% of the strains had active efflux pump, after the effect of 1/2 minimum inhibitory concentration synergistic of Z. multiflora and L. stoechas essential oils, the activity of efflux pumps was inhibited.

Conclusion:

The combination of Z. multiflora and L. stoechas essential oils against MDR A. baumannii strains were additive antibacterial effects. It was also found that these compounds, as inhibitors of efflux pumps, could also be used to suppress MDR A. baumannii isolated.
Gender Differences in Cancer Patients’ Preferences for Truth-Telling in Taiwan
Authors: Chen Shih-Ying , Fujimori Maiko , Wang Hung-Ming , Tang Woung-Ru
Published: July 2020

Background

There is a lack of studies investigating gender differences in cancer truth-telling, especially from the Asia Pacific countries.

Objective

The aim of this study was to compare preferences for cancer truth-telling between male and female cancer patients in Taiwan.

Methods

We used a quantitative cross-sectional design. Cancer patients (aged ≥18 years) were enrolled from 6 hospitals across Taiwan. A Taiwanese version of the Japanese truth-telling questionnaire was used to collect data. Multiple regression and independent t test were used for analysis.

Results

A total of 590 patients (49.6% male, 50.4% female) participated in this study. A multiple regression showed no gender differences in total scale and subscales (setting, method of disclosure, additional information, and emotional support). However, in item analysis, we found that female patients preferred detailed medical information (t = −1.973, P = .049). Both male and female patients preferred to know their medical condition (t = −1.259, P = .209), direct and frank truth-telling (t = −0.262, P = .794), and assistance in treatment decision-making (t = −0.467, P = .641). There was no gender difference in willingness to know the life expectancy (t = −0.769, P = .442) and families’ presence during truth-telling (t = −0.416, P = .678).

Conclusion

Few gender differences exist in the preferences of truth-telling for cancer patients.

Implications for Practice

Our findings can increase the sensitivity of truth-telling among nurse and other healthcare personnel when taking care of cancer patients of different genders and thereby likely improve the quality of cancer care.
Epidemiologic Treatment for Contacts to Neisseria gonorrhoeae and Chlamydia trachomatis Infection in Sexually Transmitted Disease Clinic Patients in Seattle, WA; 1994 to 2018
Authors: Rowlinson Emily , Golden Matthew R. , Berzkalns Anna , Thibault Christina , Barbee Lindley A.
Published: July 2020

Introduction

Current Centers for Disease Control and Prevention guidelines recommend that clinicians empirically treat the sex partners of persons with Neisseria gonorrhoeae (GC) or Chlamydia trachomatis (CT) infection before confirming that they are infected. It is possible that this practice, known as epidemiologic treatment, results in overtreatment for uninfected persons and may contribute to development of antimicrobial resistance. We sought to quantify the number of patients who received epidemiologic treatment and the proportion of those who were overtreated.

Methods

We reviewed records from a municipal sexually transmitted disease clinic in Seattle, WA, from 1994 to 2018 to identify visits by asymptomatic patients seeking care because of sexual contact to a partner with GC and/or CT. We defined overtreatment as receipt of antibiotic(s) in the absence of a positive GC/CT test result and calculated the proportions of contacts epidemiologically treated and tested positive for GC/CT and overtreated in five 5-year periods stratified by sex and gender of sex partner. We used the Cochran-Armitage test to assess for temporal trends.

Results

The number of asymptomatic contacts epidemiologically treated for GC/CT increased from 949 to 3159 between the 1994–1998 and 2014–2018 periods. In 2014–2018, 55% of persons were overtreated, most (82.1%) of these were men who have sex with men (MSM). The proportion of MSM overtreated decreased from 74% to 65% (P < 0.01), but the total number of overtreated MSM increased from 172 to 1428.

Discussion

A high proportion of persons receiving epidemiologic treatment of GC/CT are uninfected. The current practice of routinely treating all sex partners of persons with GC/CT merits reconsideration in light of growing antimicrobial resistance.
Impacts of Human Papillomavirus Immunization Programs on Rates of Anogenital Warts in British Columbia, Canada, 2000 to 2017
Authors: Lukac Christine D. , Donken Robine , Otterstatter Michael , Mazo Olga , Wong Stanley , Marra Fawziah , Smith Laurie , Naus Monika , Money Deborah , Krajden Mel , Grennan Troy , Gilbert Mark , Wong Jason , Ogilvie Gina S.
Published: July 2020

Background

In 2008, British Columbia (BC) implemented a school-based quadrivalent human papillomavirus (HPV-4) immunization program for girls born in 1994 or later. In 2015, an expanded clinic-based program included men who report sex with men (MSM) born in 1989 or later. To evaluate the impacts of HPV-4 programs on anogenital warts (AGWs), diagnosis rates were measured among women who report sex with men (WSM), men who report sex with women (MSW), and MSM.

Methods

Diagnoses of AGW were ascertained from 16 sexually transmitted infection clinics. Rates were calculated as new AGW diagnoses over person-years (py) at risk and stratified by age group, calendar period, and birth cohort. Adjusted relative rates (aRR) were estimated using multivariable Poisson regression.

Results

There were 204,832 clinic visits by 85,158 individuals: 28,366 (33%) WSM, 35,688 (42%) MSW, and 14,534 (17%) MSM. After adjusting for age and period, AGW rates in the 1994–1996 birth cohort decreased by 56% overall (1.21 vs. 2.72 cases/100 py; aRR, 0.44; 95% confidence interval [CI], 0.34–0.59), 65% among WSM (0.97 vs. 2.77 cases/100 py; aRR, 0.35; 95% CI, 0.22–0.57), 58% among MSW (1.60 vs. 3.78 cases/100 py; aRR, 0.42; 95% CI, 0.28–0.65), and 41% among MSM (1.14 vs. 1.19 cases/100 py; aRR, 0.59; 95% CI, 0.38–0.91) versus the 1991–1993 birth cohort.

Conclusions

The HPV-4 programs had significant impacts on lowering AGW rates in BC. The greatest decrease was among WSM eligible for the school-based program, followed by birth cohorts of men who likely have sex with HPV-4 eligible women. The smallest decrease among MSM may reflect the later introduction of the clinic-based program.
PD-1 and PD-L1 Immunohistochemistry as a Diagnostic Tool for Classic Hodgkin Lymphoma in Small-volume Biopsies
Authors: Volaric Ashley , Bacchi Carlos E. , Gru Alejandro A.
Published: July 2020

It is becoming increasingly important to obtain detailed diagnostic information on small-volume tissue biopsies, such as core needle biopsies. This is particularly crucial in the workup and diagnosis of classic Hodgkin lymphoma (CHL) and other morphologically similar lymphomas such as T-cell/histiocyte-rich large B-cell lymphoma (THRLBL), where small-volume lymph node biopsies often represent the frontline tissue source, and the differential diagnosis includes a reactive process. Immunohistochemical markers could be helpful to differentiate CHL from reactive lymph node changes (RLN) in this setting. The use of programmed cell death-1 (PD-1) and its ligand (PD-L1) immunohistochemistry has historically focused on prognostic and therapeutic value when evaluating CHL. However, the present study seeks to determine the diagnostic utility of these markers in core needle biopsies of CHL (25), THRLBL (3), and RLN (31). The cases of CHL and THRLBL were previously diagnosed and confirmed with standard immunohistochemistry, allowing the utility of PD-1 and PD-L1 to be tested in this setting. Different PD-1 and PD-L1 expression patterns were observed between the reactive process of RLN and the malignant lymphomas (CHL and THRLBL). CHL cases overall showed the greatest expression of PD-L1 within the malignant Reed-Sternberg cell population, with 40% of CHL cases exhibiting >50% PD-L1 expression. This degree of PD-L1 expression was not seen in the lymphocytic cell population of any RLN (P<0.001). Conversely, CHL cases showed an overall lower expression of PD-1, as 96% of CHLs had <5% PD-1 expression in Reed-Sternberg cells compared with only 10% expression within the lymphocytic population of RLN (P<0.001). THRLBL cases followed a similar trend to CHL. These results demonstrate that upfront PD-1 and PD-L1 immunohistochemistry can aid in the diagnosis of CHL in small-volume tissue biopsies.
Initial Results of the Use of a Standardized Diagnostic Criteria for Chest Computed Tomography Findings in Coronavirus Disease 2019
Authors: Miranda Magalhães Santos João Manoel , Paula Alves Fonseca Ana , Pinheiro Zarattini Anastacio Eduardo , Formagio Minenelli Fernanda , Furtado de Albuquerque Cavalcanti Conrado , Borges da Silva Teles Gustavo
Published: July 2020

Objective

The objective of this study was to assess the initial results of chest computed tomography (CT) standardized diagnostic criteria proposed by the Radiological Society of North America in coronavirus disease 2019 (COVID-19) compared with reverse transcription–polymerase chain reaction (RT-PCR).

Methods

Seventy-one patients who underwent RT-PCR test for COVID-19 and chest CT within an interval of 4 days or less were included. Seventy-five CTs were reviewed and classified as typical, indeterminate, or atypical appearance or negative for pneumonia by 2 radiologists. With RT-PCR as reference standard, the performance of the CT diagnostic criteria in diagnosing COVID-19 was assessed.

Results

The prevalence of positive RT-PCR was 45.1%. It was obtained a sensitivity of 83% (95% confidence interval [CI], 78%–89%), a specificity of 97% (95% CI, 92%–99%), an accuracy of 91% (95% CI, 85%–96%), a positive predictive value of 97% (95% CI, 91%–99%), and a negative predictive value of 86% (95% CI, 80%–92%). The diagnostic performance was excellent, considering the area under the curve of 0.92 (95% CI, 0.84–0.99).

Conclusions

Chest CT standardized diagnostic criteria had high specificity and positive predictive value for the diagnosis of COVID-19 when presenting a typical appearance.
Failure to Cure in Patients Undergoing Surgery for Esophageal Carcinoma: Hospital of Surgery Influences Prospects for Cure
Authors: Voeten Daan M. , van der Werf Leonie R. , Wijnhoven Bas P. L. , van Hillegersberg Richard , van Berge Henegouwen Mark I.
Published: July 2020

Objective:

This study aimed to describe failure to cure in terms of incidence, hospital variation, and as an outcome parameter for salvage esophagectomy.

Summary Background Data:

Failure to cure is a composite outcome measure that could be used for hospital comparison in esophageal carcinoma care.

Methods:

All patients registered in the Dutch Upper GI Cancer Audit who underwent potentially curative esophageal carcinoma surgery in 2011 to 2018, were included in this nationwide cohort study. Failure to cure was defined as: 1) no surgical resection due to intraoperative metastasis or locally irresectable tumor, 2) macroscopically or microscopically incomplete resection, or 3) 30-day/in-hospital mortality. Association of baseline characteristics with failure to cure was analyzed using multivariable logistic regression in the total population and in salvage patients.

Results:

Some 5894 patients from 22 hospitals were included, of whom 630 (10.7%) had failure to cure (hospital variation [5.5%–19.1%]). Higher age, preoperative weight loss, higher ASA-score, higher N-stage, neoadjuvant chemotherapy, or no neoadjuvant therapy (compared with neoadjuvant chemoradiotherapy), open surgery, and resection before 2014 were associated with failure to cure. After case-mix correction, 2 hospitals had statistically significant higher failure to cure percentages, whereas 2 had lower percentages. Of 151 salvage esophagectomy patients, 32.5% had failure to cure. The failure to cure rate after salvage surgery was 27.6% in high-volume hospitals and 47.6% in medium-volume hospitals.

Conclusions:

The incidence of failure to cure was 10.7%. Given the significant hospital variation in the percentage of failure to cure, improvement is needed. Since salvage procedures are more often successful in high-volume hospitals, further centralization of this procedure is warranted.
Multitasking and Time Pressure in the Operating Room
Authors: Modi Hemel N. , Singh Harsimrat , Darzi Ara , Leff Daniel R.
Published: July 2020

Objective:

To assess the impact of multitasking and time pressure on surgeons’ brain function during laparoscopic suturing.

Summary Background Data:

Recent neuroimaging evidence suggests that deterioration in surgical performance under time pressure is associated with deactivation of the prefrontal cortex (PFC), an area important for executive functions. However, the effect of multitasking on operator brain function remains unknown.

Methods:

Twenty-nine surgical residents performed an intracorporeal suturing task under four conditions: 1) self-paced suturing, 2) time-pressured suturing, 3) self-paced suturing plus decision-making, and 4) time-pressured suturing plus decision-making. Subjective workload was quantified using the Surgical Task Load Index. Technical skill was objectively assessed using task progression scores, error scores, leak volumes, and knot tensile strengths. PFC activation was measured using optical neuroimaging.

Results:

Compared with self-paced suturing, subjective workload (au) was significantly greater in time-pressured suturing (146.0 vs 196.0, P < 0.001), suturing with decision-making (146.0 vs 182.0, P < 0.001), and time-pressured suturing with decision-making (146.0 vs 227.0, P < 0.001). Technical performance during combined suturing and decision-making tasks was inferior to suturing alone under time pressure or self-paced conditions (P < 0.001). Significant dorsolateral PFC (DLPFC) activations were observed during self-paced suturing, and ventrolateral PFC (VLPFC) deactivations were identified during time-pressured suturing. However, suturing in conjunction with decision-making resulted in significant deactivation across both the VLPFC and DLPFC (P < 0.05). Random effects regression analysis confirmed decision-making predicts VLPFC and DLPFC deactivation (z = −2.62, P < 0.05).

Conclusions:

Performance degradation during high workload conditions is associated with deactivation of prefrontal regions important for attentional control, working memory, and cognitive flexibility, particularly during tasks involving simultaneous motor and cognitive engagement.
Gastroesophageal resuscitative occlusion of the aorta: Physiologic tolerance in a swine model of hemorrhagic shock
Authors: Tiba Mohamad H. , McCracken Brendan M. , Colmenero Carmen I. , Plott Jeffery S. , Leander Danielle C. , Greer Nicholas L. , Wang Stewart C. , Shih Albert J. , Eliason Jonathan L. , Ward Kevin R.
Published: July 2020

BACKGROUND

Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been shown to be effective for management of noncompressible torso hemorrhage. However, this technique requires arterial cannulation, which can be time-consuming and not amendable to placement in austere environments. We present a novel, less invasive aortic occlusion device and technique designated gastroesophageal resuscitative occlusion of the aorta (GROA). In this study, we aimed to characterize the physiological tolerance and hemodynamic effects of a prototype GROA device in a model of severe hemorrhagic shock and resuscitation and compare with REBOA.

METHODS

Swine (N = 47) were surgically instrumented for data collection. A 35% controlled arterial hemorrhage was followed by randomizing animals to 30-minute, 60-minute, or 90-minute interventions of GROA, REBOA, or control. Following intervention, devices were deactivated, and animals received whole blood and crystalloid resuscitation. Animals were monitored for an additional 4 hours.

RESULTS

All animals except one GROA 90-minute application survived the duration of their intervention periods. Survival through resuscitation phase in GROA, REBOA, and control groups was similar in the 30-minute and 60-minute groups. The 90-minute occlusion groups exhibited deleterious effects upon device deactivation and reperfusion with two GROA animals surviving and no REBOA animals surviving. Mean (SD) arterial pressure in GROA and REBOA animals increased across all groups to 98 (31.50) mm Hg and 122 (24.79) mm Hg, respectively, following intervention. Lactate was elevated across all GROA and REBOA groups relative to controls during intervention but cleared by 4 hours in the 30-minute and 60-minute groups. Postmortem histological examination of the gastric mucosa revealed mild to moderate inflammation across all GROA groups.

CONCLUSION

In this study, the hemodynamic effects and physiological tolerance of GROA was similar to REBOA. The GROA device was capable of achieving high zone II full aortic occlusion and may be able to serve as an effective method of aortic impingement.
Downstream hospital system effects of a comprehensive trauma recovery services program
Authors: DeMario Belinda , Kalina Mark J. , Truong Evelyn , Hendrickson Sarah , Tseng Esther S. , Claridge Jeffrey A. , Vallier Heather , Ho Vanessa P.
Published: July 2020

BACKGROUND

Trauma patients are often noted to have poor compliance but high recidivism and readmission rates. Participation in a trauma recovery services (TRS) program, which provides peer support and other psychosocial resources, may impact the trajectory of patient recovery by decreasing barriers to follow-up. We hypothesized that TRS participants would have greater downstream nonemergent use of our hospital system over the year following trauma, manifested by more positive encounters, fewer negative encounters, and lower emergency department (ED) charges.

METHODS

We studied trauma survivors (March 2017 to March 2018) offered TRS. Hospital encounters and charges 1 year from index admission were compared between patients who accepted and declined TRS. Positive encounters were defined as outpatient visits and planned admissions; negative encounters were defined as no shows, ED visits, and unplanned admissions. Charges were grouped as cumulative ED and non-ED charges (including outpatient and subsequent admission charges). Adjusted logistic and linear regression analyses were used to identify factors associated with positive/negative encounters and ED charges.

RESULTS

Of 511 identified patients (68% male; injury severity score, 14 [9–19]), 362 (71%) accepted TRS. Trauma recovery services patients were older, had higher injury severity, and longer index admission length of stay (all p < 0.05). After adjusting for confounders, TRS patients were more likely to have at least one positive encounter and were similarly likely to have negative encounters as patients who declined services. Total aggregate charges for this group was US $74 million, of which US $30 million occurred downstream of the index admission. Accepting TRS was associated with lower ED charges.

CONCLUSION

A comprehensive TRS program including education, peer mentors, and a support network may provide value to the patient and the health care system by reducing subsequent care provided by the ED in the year after a trauma without affecting nonemergent care.

LEVEL OF EVIDENCE

Therapeutic/care management, level IV.
Therapeutic strategies for Huntington's disease
Authors: Estevez-Fraga Carlos , Flower Michael D. , Tabrizi Sarah J.
Published: July 2020

Purpose of review

Huntington's disease is a fatal autosomal dominant neurodegenerative disorder caused by a trinucleotide expansion in theHTTgene, and current therapies focus on symptomatic treatment. This review explores therapeutic approaches that directly target the pathogenic mutation, disruptHTTmRNA or its translation.

Recent findings

Zinc-finger transcription repressors and CRISPR-Cas9 therapies targetHTTDNA, thereby preventing all downstream pathogenic mechanisms. These therapies, together with RNA interference (RNAi), require intraparenchymal delivery to the brain in viral vectors, with only a single delivery potentially required, though they may carry the risk of irreversible side-effects.

Along with RNAi, antisense oligonucleotides (ASOs) target mRNA, but are delivered periodically and intrathecally. ASOs have safely decreased mutant huntingtin protein (mHTT) levels in the central nervous system of patients, and a phase 3 clinical trial is currently underway.

Finally, orally available small molecules, acting on splicing or posttranslational modification, have recently been shown to decrease mHTT in animal models.

Huntingtin-lowering approaches act upstream of pathogenic mechanisms and therefore have a higha priorilikelihood of modifying disease course. ASOs are already in late-stage clinical development, whereas other strategies are progressing rapidly toward human studies.
Genes associated with liver damage signalling pathways may impact the severity of COVID-19 symptoms in Spanish and Italian populations
Authors: Moya Leire , Farashi Samaneh , Suravajhala Prashanth N , Janaththani Panchadsaram , Batra Jyotsna
Published: July 2020

Aim

The novel SARS-CoV-2 virus, which causes the COVID-19 disease, has infected more than 10 million people and caused 500K deaths worldwide. In Europe, over 2 million confirmed cases have been reported, while nearly 200K people have died from the disease. Despite strict containment measures in Spain and Italy after the first reported COVID-19 patient, these two countries have remained in the top five European nations with the highest mortality rate for over two months. We hypothesised that a genetic mechanism could partially explain the poor survival outcome observed in these two countries.

Methods

An extensive literature search to identify human candidate genes linked to SARS-CoV infection, host immune evasion and disease aggressiveness was carried out. Pathway analysis (IPA) was performed to select the most significantly associated canonical signalling pathways with the genes of interest. The genetic variants’ at these genes with ±1Mb flanking region was extracted (GRCh37/hg19 built). Over 80 million single nucleotide polymorphisms (SNPs) were analysed in genome-wide data of 2,504 individuals (1000 genomes, phase III,https://www.internationalgenome.org/). Principal component (PC) analysis was performed, ancestry by the whole genome was inferred and subsets of the regions of interest were extracted (PLINK v1.9b,http://pngu.mgh.harvard.edu/purcell/plink/). PC1 to PC20 values from five European ancestries, including the Spanish and Italian populations, were used for PC analysis. Gene function predictions were run with our genes of interest as a query to the GeneMANIA Cytoscape plugin (https://genemania.org/).

Results

A total of 437 candidate genes associated with SARS were identified, including 21 correlated with COVID-19 aggressiveness. The two most significant pathways associated with all 437 genes (Caveolar-mediated EndocytosisandMSP-RON Signalling) did not show any segregation at the population level. However, the most significant canonical pathway associated with genes linked to COVID-19 aggressiveness, theHepatic Fibrosis and Hepatic Stellate Cell Activation,showed population-specific segregation. Both the Spanish and Italian populations clustered together from the rest of Europe. This was also observed for the Finnish population but in the opposite direction. These results suggest some of the severe COVID-19 cases reported in Spain and Italy could be partially explained by a pre-existing liver condition (especially liver cancer) and/or may lead to further COVID-19 related liver complications.
Reduced phenotypic plasticity evolves in less predictable environments
Authors: Leung Christelle , Rescan Marie , Grulois Daphné , Chevin Luis-Miguel
Published: July 2020

Phenotypic plasticity is a prominent mechanism for coping with variable environments, and a key determinant of extinction risk. Evolutionary theory predicts that phenotypic plasticity should evolve to lower levels in environments that fluctuate less predictably, because they induce mismatches between plastic responses and selective pressures. However this prediction is difficult to test in nature, where environmental predictability is not controlled. Here, we exposed 32 lines of the halotolerant microalgaDunaliella salinato ecologically realistic, randomly fluctuating salinity, with varying levels of predictability, for 500 generations. We found that morphological plasticity evolved to lower levels in lines that experienced less predictable environments. Evolution of plasticity mostly concerned phases with slow population growth, rather than the exponential phase where microbes are typically phenotyped. This study underlines that long-term experiments with complex patterns of environmental change are needed to test theories about population responses to altered environmental predictability, as currently observed under climate change.
CEREBRUM-7T: Fast and Fully-volumetric Brain Segmentation of 7 Tesla MR Volumes
Authors: Svanera Michele , Benini Sergio , Bontempi Dennis , Muckli Lars
Published: July 2020

Ultra high-field MRI enables sub-millimetre resolution imaging of the human brain, allowing for the resolution of functional circuits at the meso-scale of cortical layers. An essential step in many functional and structural neuroimaging studies is segmentation, the operation of partitioning the MR brain images to delineate anatomical structures. Despite recent efforts in brain imaging analysis, the literature lacks of accurate and fast methods for segmenting 7 Tesla (7T) brain MRI. We here presentCEREBRUM-7T, an optimised end-to-end Convolutional Neural Network (CNN) architecture, that allows for the segmentation of a whole 7T T1wMRI brain volume at once, thus overcoming the drawbacks of partitioning the volume into 2D or 3D tiles. Training is performed in a weakly supervised fashion, exploiting labelling with errors obtained with automatic state-of-the-art methods. The trained model is able to produce accurate multi-structure segmentation masks on six different classes in only a few seconds. In the experimental part, a combination of objective numerical evaluations and subjective analysis carried out by experienced neuroimaging users, confirms that the proposed solution outperforms the training labels it was trained on in segmentation accuracy, and is suitable for neuroimaging studies, such as layer fMRI studies. Taking advantage of a fine-tuning operation on a reduced set of volumes, we also show how it is possible to efficiently and effectively applyCEREBRUM-7Tto data from different sites. Furthermore, to allow replicability and encourage extensions, we release the code, 7T data (142 volumes), and other materials, including the training labels and the Turing test.
DeepForest: A Python package for RGB deep learning tree crown delineation
Authors: Weinstein Ben. G. , Marconi Sergio , Aubry-Kientz Mélaine , Vincent Gregoire , Senyondo Henry , White Ethan
Published: July 2020

Remote sensing of forested landscapes can transform the speed, scale, and cost of forest research. The delineation of individual trees in remote sensing images is an essential task in forest analysis. Here we introduce a new Python package, DeepForest, that detects individual trees in high resolution RGB imagery using deep learning.

While deep learning has proven highly effective in a range of computer vision tasks, it requires large amounts of training data that are typically difficult to obtain in ecological studies. DeepForest overcomes this limitation by including a model pre-trained on over 30 million algorithmically generated crowns from 22 forests and fine-tuned using 10,000 hand-labeled crowns from 6 forests.

The package supports the application of this general model to new data, fine tuning the model to new datasets with user labeled crowns, training new models, and evaluating model predictions. This simplifies the process of using and retraining deep learning models for a range of forests, sensors, and spatial resolutions.

We illustrate the workflow of DeepForest using data from the National Ecological Observatory Network, a tropical forest in French Guiana, and street trees from Portland, Oregon.
ThermoFRET: A novel nanoscale G protein coupled receptor thermostability assay functional in crude solubilised membrane preparations
Authors: Tippett David N , Hoare Brad , Miljus Tamara , Sykes David A , Veprintsev Dmitry B.
Published: July 2020

Sensitive protein stability assays for membrane proteins are crucial for developing purification protocols, for structural and biophysical characterisation and drug discovery. Here, we describe a novel high-throughput 384-well FRET-based thermostability methodology, ThermoFRET, allowing for the ultrasensitive determination of G protein coupled receptor (GPCR) stability. This method measures FRET between a terbium-cryptate labelled GPCR and BODIPY-FL-Cystine, a thiolreactive dye that reacts with cysteine residues exposed upon protein unfolding in response to thermal denaturation. ThermoFRET is functional in crude solubilised membrane preparations, without protein purification and can detect receptor stabilising ligands, making it ideally suited for orphan receptor screening.
Optogenetic activation of muscle contractionin vivo
Authors: Ganji Elahe , Chan C. Savio , Ward Christopher W. , Killian Megan L.
Published: July 2020

Optogenetics is an emerging alternative to traditional electrical stimulation to initiate action potentials in activatable cells both ex vivo and in vivo. Optogenetics has been commonly used in mammalian neurons and more recently, it has been adapted for activation of cardiomyocytes and skeletal muscle. Therefore, the aim of this study was to evaluate the stimulation feasibility and sustain isometric muscle contraction and limit decay for an extended period of time (1s), using non-invasive transdermal light activation of skeletal muscle (triceps surae) in vivo. We used inducible Cre recombination to target expression of Channelrhodopsin-2 (ChR2(H134R)-EYFP) in skeletal muscle (Acta1-Cre) in mice. Fluorescent imaging confirmed that ChR2 expression is localized in skeletal muscle and does not have specific expression in sciatic nerve branch, therefore, allowing for non-nerve mediated optical stimulation of skeletal muscle. We induced muscle contraction using transdermal exposure to blue light and selected 10Hz stimulation after controlled optimization experiments to sustain prolonged muscle contraction. Increasing the stimulation frequency from 10Hz to 40Hz increased the muscle contraction decay during prolonged 1s stimulation, highlighting frequency dependency and importance of membrane repolarization for effective light activation. Finally, we showed that optimized pulsed optogenetic stimulation of 10 Hz resulted in comparable ankle torque and contractile functionality to that of electrical stimulation. Our results demonstrate the feasibility and repeatability of non-invasive optogenetic stimulation of muscle in vivo and highlight optogenetic stimulation as a powerful tool for non-invasive in vivo direct activation of skeletal muscle.
Parallel evolution of UbiA superfamily proteins into aromaticO-prenyltransferases in plants
Authors: Munakata Ryosuke , Olry Alexandre , Takemura Tomoya , Tatsumi Kanade , Ichino Takuji , Villard Cloé , Kageyama Joji , Kurata Tetsuya , Nakayasu Masaru , Jacob Florence , Koeduka Takao , Yamamoto Hirobumi , Moriyoshi Eiko , Matsukawa Tetsuya , Grosjean Jeremy , Krieger Célia , Sugiyama Akifumi , Mizutani Masaharu , Bourgaud Frédéric , Hehn Alain , Yazaki Kazufumi
Published: July 2020

Plants produce approximately 300 aromatic molecules enzymatically linked to prenyl side chains via C-O bonds. TheseO-prenylated aromatics have been found in taxonomically distant plant taxa as compounds beneficial or detrimental to human health, withO-prenyl moieties often playing crucial roles in their biological activities. To date, however, no plant gene encoding an aromaticO-prenyltransferase (O-PT) has been described. This study describes the isolation of an aromaticO-PT gene,CpPT1, belonging to the UbiA superfamily, from grapefruit (Citrus×paradisi,Rutaceae). This gene is responsible for the biosynthesis ofO-prenylated coumarin derivatives that alter drug pharmacokinetics in the human body. Another coumarinO-PT gene of the same protein family was identified inAngelica keiskei, an apiaceous medicinal plant containing pharmaceutically activeO-prenylated coumarins. Phylogenetic analysis of theseO-PTs suggested that aromaticO-prenylation activity evolved independently from the same ancestral gene in these distant plant taxa. These findings shed light on understanding the evolution of plant secondary metabolites via the UbiA superfamily.
Enhanced Neuronal Activity and Asynchronous Calcium Transients Revealed in a 3D Organoid Model of Alzheimer’s Disease
Authors: Yin Juan , VanDongen Antonius M.
Published: July 2020

Advances in the development of three-dimensional (3D) brain organoids maintainedin vitrohave provided excellent opportunities to study brain development and neurodegenerative disorders, including Alzheimer’s disease (AD). However, there remains a need to generate AD organoids bearing patient-specific genomic backgrounds that can functionally recapitulate key features observed in the AD patient’s brain. To address this need, we successfully generated cerebral organoids from human pluripotent stem cells (hPSCs) derived from a familial AD patient with a mutation in presenilin 2 (PSEN2). An isogenic control hPSC line was generated using CRISPR-Cas9 technology. Both organoids were characterized by analysing their morphology, Aβ42/Aβ40 ratio and functional neuronal network activity. It was found that AD organoids had a higher Aβ42/Aβ40 ratio, asynchronous calcium transients and enhanced neuronal hyperactivity, successfully recapitulating some aspects of AD pathology. Therefore, our study presents a promising organoid-based biosystem for the study of the pathophysiology of AD and a platform for drug development for neurodegenerative disorders.
Pharmacological class interventions for benzodiazepine withdrawal discontinuation: a meta-analysis
Authors: Fluyau Dimy , Revadigar Neelambika , Mitra Paroma , Pierre Christopher G.
Published: July 2020

Background

Long-term benzodiazepine (BZD) use may lead to dependence, addiction, and neuropsychiatric disturbances. BZD discontinuation can cause severe withdrawal symptoms and resurgence of premorbid conditions. There are guidelines on how to stop BZD if it is necessary.

Pharmacological management is an option among several other recommendations, but its benefit remains unclear. This study investigates whether certain pharmacological classes can manage or facilitate BZD withdrawal beyond BZD itself.

Methods

Data collected from (1985 to 2018) in Google Scholar, Medline Ovid, Scopus, PsychInfo, ClinicalTrials.gov, Cochrane Review Database, Embase, Scopus, Pubmed, and Proquest databases: involved controlled clinical trials on drugs studied for BZD withdrawal discontinuation. Single drugs were clustered into their pharmacological class (domain). The Oxford Quality Scoring System assessed the quality of a trial. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) was used for clinical practice recommendations. For publication bias, we visually inspected the Funnel plot. We adopted the Cochrane Risk of Bias Tool to assess biases inherent to individual trials. The standardized mean difference measured the magnitude of the benefit of a pharmacological class.

Results

We analyzed forty-nine controlled trials of 2815 assigned participants. Of fourteen classes, the BZD receptor antagonist class (d 0.671, CI 0.199 -1.143, p=0.005, I2=0),5-HT1A receptor partial agonist, and the glutamate class seemed to have the potentiality to manage BZD withdrawal discontinuation clinically. Around 61 % of the trials received an Oxford Quality score of three, 86% of the trials were granted a GRADE recommendation low. About 29 trials were at low risk of bias in general.

Conclusions

Even though we could not prove that the pharmacological classes of drugs we analyzed for the clinical management of BZD withdrawal discontinuation were efficacious, our investigation showed that some of these classes have the potentiality to manage BZD withdrawal discontinuation and clinically facilitate the process when it is necessary, relevant, and recommended based on established guidelines. Further investigations are warranted to support our findings.
Variation of the vaginal microbiome during and after pregnancy in Chinese women
Authors: Zhang Xiaoai , Zhai Qingzhi , Wang Jinfeng , Ma Xiuling , Xing Bo , Fan Hang , Gao Zhiying , Zhao Fangqing , Liu Wei
Published: July 2020

A more complete profiling of vaginal microbial communities and their variability enables a more accurate description of women microbiome. However, there is a distinct lack of information regarding the Chinese women. Composition of the vaginal microbiota during pregnancy and 6 weeks postpartum of 454 Chinese women thus was characterized in this study by sequencing V3-V4 regions of the 16S ribosomal RNA (rRNA). It showed that the vaginal microbiome varied during pregnancy and postpartum in response to abortion history, hypertensive disorders (HBP), delivery mode and maternal age. Co-variation of 21 bacterial taxa, including Lactobacillus and two of its species, may account for the common characteristics of vaginal microbiome under different medical histories and pregnancy outcomes. On the contrary, discriminant bacteria were significantly different between premature rupture of membranes related preterm birth (PROM-PTB) and non-PROM related PTB, and community state type (CST) I without any predominant Lactobacillus species in microbiota was more prevalent during pregnancy in PROM-PTB, suggesting that specific bacteria could be considered to distinguish different types of PTB. Through adding the data from Chinese women, the study will enrich the knowledge of human microbiome and likewise contribute to a better understanding of the association between the vaginal microbiome and reproductive health.