In Vitro Comparison of Two Barbed Suture Configurations for Flexor Tendon Repair.

Abstract: Purpose  The current study compares the strength of a previously studied technique for flexor tendon repair with barbed sutures to an experimental approach that aligns all the barbs to oppose distraction. Methods  Twelve flexor tendons from cadaveric specimens were mechanically tested following repair of simulated zone II tendon injuries. Two repair techniques utilizing barbed sutures were studied: the Marrero-Amadeo four-core barbed suture approach and the experimental configuration with all barbs on four cores opposing distraction. Maximum applied load at failure, that is, ultimate load, and 2-mm gap force were compared between the two repair techniques, both as raw values and after normalization to cross-sectional area of the intact tendon. Statistical testing was performed using t -tests and Mann-Whitney U -tests, where appropriate, with a significance level of 0.05. Results  The ultimate loads, raw (58.2 N) and normalized (4.8 N/mm 2 ), were significantly larger for the Marrero-Amadeo repair than the proposed experimental approach (35.6 N and 2.7 N/mm 2 ; p  < 0.05). No significant differences were identified for 2-mm gap force. Conclusion  The innovation of suturing to align all barbs to oppose distraction does not improve strength of the repaired tendon. The Marrero-Amadeo technique was found to have superior strength for use in traumatic zone II flexor tendon injuries.

Engel|Jamie L|JL|
Gabra|Joseph N|JN|
Esterle|Andrew R|AR|
Lanzinger|William D|WD|
Elias|John J|JJ|

barbed suture
flexor tendon repair
strength
mechanical testing


Acceptability of drug detection monitoring among participants in an open-label pre-exposure prophylaxis study.

Abstract: In the world of HIV pre-exposure prophylaxis (PrEP) research, there is emerging interest in providing study participants with pharmacokinetic results from drug level testing to guide adherence counseling. The iPrEx randomized control trial was the first study to produce meaningful results of PrEP in humans. In the iPrEx open-label extension (OLE) study, blood plasma samples collected in the first 12 weeks of study participation were tested for the presence of tenofovir/emtricitabine--the drugs which compromise PrEP. Study clinicians shared results (detectable/undetectable) with participants at their 24-week visit. We evaluated the acceptability of receiving these results among a subset of iPrEx OLE participants. We conducted in-depth interviews (n = 59) with participants (those with and those without drug detected) enrolled in Boston, Chicago, and San Francisco to assess their experiences with receiving drug detection feedback. Incorporating drug detection results into the clinical study visit was well received and no negative reactions were expressed. For about half of participants, receiving their drug detection lab result was useful while for others it was not important. In a few cases, no drug detected results led to increased efforts to take PrEP consistently and in most cases enhanced open discussion of missed doses. Participants reported a desire for greater specificity, particularly quantitative drug levels needed for protection. We recommend exploring strategies to increase the salience of drug level results, including using feedback to target adherence counseling, and reducing the time between specimen collection, testing, and receipt of results. Future studies should evaluate the feasibility and impact of providing more specific quantitative drug levels using biomarkers of longer term PrEP exposure, i.e., hair/dried blood spots.

Koester|Kimberly A|KA|
Liu|Albert|A|
Eden|Christopher|C|
Amico|K Rivet|KR|
McMahan|Vanessa|V|
Goicochea|Pedro|P|
Hosek|Sybil|S|
Mayer|Kenneth H|KH|
Grant|Robert M|RM|

D010342:Patient Acceptance of Health Care

drug detection monitoring
pre-exposure prophylaxis
HIV
adherence
qualitative methods


Neurocognitive Development of Motivated Behavior: Dynamic Changes across Childhood and Adolescence.

Abstract: The ability to anticipate and respond appropriately to the challenges and opportunities present in our environments is critical for adaptive behavior. Recent methodological innovations have led to substantial advances in our understanding of the neurocircuitry supporting such motivated behavior in adulthood. However, the neural circuits and cognitive processes that enable threat- and reward-motivated behavior undergo substantive changes over the course of development, and these changes are less well understood. In this article, we highlight recent research in human and animal models demonstrating how developmental changes in prefrontal-subcortical neural circuits give rise to corresponding changes in the processing of threats and rewards from infancy to adulthood. We discuss how these developmental trajectories are altered by experiential factors, such as early-life stress, and highlight the relevance of this research for understanding the developmental onset and treatment of psychiatric disorders characterized by dysregulation of motivated behavior.

development
motivation
threat
reward
dopamine
early life stress
prefrontal cortex


Maternal separation in childhood and hair cortisol concentrations in late adulthood.

Abstract:
BACKGROUND
Parent-child separation has been shown to increase the risk of a range of mental and physical health conditions later in life. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may help to explain this association. However, few studies have examined the effect of maternal separation on cortisol in late adulthood.

METHODS
We examined the relationship between maternal separation in childhood and hair cortisol concentrations in late adulthood, using data from the Whitehall II study (n = 3969, mean age: 70 y, range: 60-83 y). Additionally, the role of childhood (adverse childhood experiences (ACEs), material disadvantage, and parenting), adult (marital status and social position), and health (health behaviors, cardiovascular health and medication, and depression) measures in this association were examined. Finally, we examined age of separation and reason for separation. Analysis was carried out using linear regression.

RESULTS
Hair cortisol concentrations (pg/mg) among participants who reported maternal separation during childhood were higher (B=0.179, 95% CI 0.041-0.317, p = 0.01) compared to their non-separated counterparts. This effect was robust to adjustment by childhood, adult, and health measures. Among participants who reported separation, age at onset and reason for separation were not significantly associated with hair cortisol concentrations.

CONCLUSION
In older age individuals, hair cortisol concentrations were higher in those who reported maternal separation during childhood. This effect was independent of a wide variety of factors suggesting that there are lifelong pathways between early life separation and HPA functioning in old age.

Maternal separation
Childhood
Hair cortisol
Late adulthood
Whitehall II
Early life stress


Prostate Cancer-associated SPOP mutations enhance cancer cell survival and docetaxel resistance by upregulating Caprin1-dependent stress granule assembly.

Abstract:
BACKGROUND
The gene encoding the E3 ubiquitin ligase substrate-binding adaptor SPOP is frequently mutated in primary prostate cancer, but how SPOP mutations contribute to prostate cancer pathogenesis remains poorly understood. Stress granules (SG) assembly is an evolutionarily conserved strategy for survival of cells under stress, and often upregulated in human cancers. We investigated the role of SPOP mutations in aberrant activation of the SG in prostate cancer and explored the relevanve of the mechanism in therapy resistance.

METHODS
We identified SG nucleating protein Caprin1 as a SPOP interactor by using the yeast two hybrid methods. A series of functional analyses in cell lines, patient samples, and xenograft models were performed to investigate the biological significance and clinical relevance of SPOP regulation of SG signaling in prostate cancer.

RESULTS
The cytoplasmic form of wild-type (WT) SPOP recognizes and triggers ubiquitin-dependent degradation of Caprin1. Caprin1 abundance is elevated in SPOP-mutant expressing prostate cancer cell lines and patient specimens. SPOP WT suppresses SG assembly, while the prostate cancer-associated mutants enhance SG assembly in a Caprin1-dependent manner. Knockout of SPOP or expression of prostate cancer-associated SPOP mutants conferred resistance to death caused by SG inducers (e.g. docetaxel, sodium arsenite and H2O2) in prostate cancer cells.

CONCLUSIONS
SG assembly is aberrantly elevated in SPOP-mutated prostate cancer. SPOP mutations cause resistance to cellular stress induced by chemtherapeutic drug such as docetaxel in prostate cancer.

Shi|Qing|Q| Zhu|Yasheng|Y| Ma|Jian|J| Chang|Kun|K| Ding|Dongling|D| Bai|Yang|Y| Gao|Kun|K| Zhang|Pingzhao|P| Mo|Ren|R| Feng|Kai|K| Zhao|Xiaying|X| Zhang|Liang|L| Sun|Huiru|H| Jiao|Dongyue|D| Chen|Yingji|Y| Sun|Yinghao|Y| Zhao|Shi-Min|SM| Huang|Haojie|H| Li|Yao|Y| Ren|Shancheng|S| Wang|Chenji|C|

D018797:Cell Cycle Proteins
D045744:Cell Line, Tumor
D002470:Cell Survival
D003594:Cytoplasmic Granules
D000077143:Docetaxel
D019008:Drug Resistance, Neoplasm
D005455:Fluorescent Antibody Technique
D006801:Humans
D008297:Male
D008954:Models, Biological
D009154:Mutation
D009687:Nuclear Proteins
D011471:Prostatic Neoplasms
D011485:Protein Binding
D059748:Proteolysis
D012097:Repressor Proteins
D013312:Stress, Physiological
D044767:Ubiquitin-Protein Ligases
D054875:Ubiquitination

Stress granules
Ubiquitination
Prostate cancer
Gene mutations


Factors Impacting Mortality in the Pre-Hospital Period After Road Traffic Accidents in Urban India.

Abstract:
BACKGROUND
India currently has the dubious distinction of experiencing the highest number of road traffic accidents in the world.

OBJECTIVES
We believe that this study on road traffic accidents may help to identify factors in the pre-hospital setting that may influence mortality rates.

PATIENTS AND METHODS
A prospective observational study was carried out in a metro area in India over a period of one year. The study included consecutive patients admitted to the trauma service after road traffic accidents. Demographic information, time and place of accident, and details regarding the vehicle and the events leading up to the hospital admission were recorded. Injury severity, management in the hospital, and final outcomes in terms of mortality were noted. The data were analyzed with SPSS software.

RESULTS
A total of 773 patients were enrolled. Of these, there were 197 deaths and 576 survivors. The majority of patients were aged 15 - 40 years (67%) and were male (87.84%). More accidents occurred at night (58.2%) than during the day (41.8%). Mortality was not significantly associated with age, sex, or time of accident. City roads (38.9%) saw more accidents than highways (26.13%), but highway accidents were more likely to be fatal. Two-wheeler riders (37.65%) and pedestrians (35.75%) formed the majority of our study population. Mortality was significantly associated with crossing the road on foot (P = 0.004). Pillion riders on two-wheeler vehicles were more likely to experience poor outcomes (relative risk [RR] = 1.9, P = 0.001). Front-seat occupants in four-wheeler vehicles were at an increased risk of not surviving the accident (61.98%; RR=2.56, P = 0.01). Lack of safety gear, such as helmets, seat belts, and airbags, was significantly associated with mortality (P = 0.05). Delays in transfers of patients to the hospital and a lack of pre-hospital emergency services was significantly associated with increased mortality (P = 0.000).

CONCLUSIONS
A lack of respect for the law, weak legislation and law enforcement, disregard for personal safety, and driving vehicles under adverse conditions are some of the leading causes of road traffic accidents. There should be an emphasis on emergency trauma care in the pre-hospital setting.

Chandrasekharan|Ananthnarayan|A|
Nanavati|Aditya J|AJ|
Prabhakar|Sandhya|S|
Prabhakar|Subramaniam|S|

Mortality
Road Traffic Accidents
India
Pre-Hospital Events


Pyrolysis molecule of Torreya grandis bark for potential biomedicine.

Abstract: Torreya grandis is a unique tree species in China. Although full use has been made of the timber, the processing and utilization of the bark has not been effective. In order to explore a new way to utilize the bark of Torreya grandis, a powder of T. grandis bark was prepared and analyzed qualitatively and quantitatively. Differential scanning calorimetry (TG) and pyrolysis gas chromatography-mass spectrometry (PY-GC/MS) revealed many bioactive components in the bark of T. grandis, such as acetic acid, 2-methoxy-4-vinyl phenol, D-mannose, and furfural. These substances have potential broad applications in the chemical industry, biomedicine, and food additives. The chemical constituents of the bark of T. grandis suggest a theoretical basis for the future development and utilization of the bark of T. grandis.

Chen|Huiling|H| Yue|Xiaochen|X| Yang|Jun|J| Lv|Chunxia|C| Dong|Shuaiwei|S| Luo|Xuefeng|X| Sun|Zhiyong|Z| Zhang|Ying|Y| Li|Baoxiang|B| Zhang|Faping|F| Gu|Haiping|H| Yang|Yafeng|Y| Zhang|Qiuling|Q| Ge|Shengbo|S| Bi|Huitao|H| Zheng|Dongfang|D| Zhao|Yong|Y| Li|Cheng|C| Peng|Wanxi|W|


Stereotactic radiosurgery for intracranial dural arteriovenous fistulas: a systematic review.

Abstract:
OBJECT
The goal of this study was to evaluate the obliteration rate of intracranial dural arteriovenous fistulas (DAVFs) in patients treated with stereotactic radiosurgery (SRS), and to compare obliteration rates between cavernous sinus (CS) and noncavernous sinus (NCS) DAVFs, and between DAVFs with and without cortical venous drainage (CVD).

METHODS
A systematic literature review was performed using PubMed. The CS DAVFs and the NCS DAVFs were categorized using the Barrow and Borden classification systems, respectively. The DAVFs were also categorized by location and by the presence of CVD. Statistical analyses of pooled data were conducted to assess complete obliteration rates in CS and NCS DAVFs, and in DAVFs with and without CVD.

RESULTS
Nineteen studies were included, comprising 729 patients harboring 743 DAVFs treated with SRS. The mean obliteration rate was 63% (95% CI 52.4%-73.6%). Complete obliteration for CS and NCS DAVFs was achieved in 73% and 58% of patients, respectively. No significant difference in obliteration rates between CS and NCS DAVFs was found (OR 1.72, 95% CI 0.66-4.46; p=0.27). Complete obliteration in DAVFs with and without CVD was observed in 56% and 75% of patients, respectively. A significantly higher obliteration rate was observed in DAVFs without CVD compared with DAVFs with CVD (OR 2.37, 95% CI 1.07-5.28; p=0.03).

CONCLUSIONS
Treatment with SRS offers favorable rates of DAVF obliteration with low complication rates. Patients harboring DAVFs that are refractory or not amenable to endovascular or surgical therapy may be safely and effectively treated using SRS.

Chen|Ching-Jen|CJ|
Lee|Cheng-Chia|CC|
Ding|Dale|D|
Starke|Robert M|RM|
Chivukula|Srinivas|S|
Yen|Chun-Po|CP|
Moosa|Shayan|S|
Xu|Zhiyuan|Z|
Pan|David Hung-Chi|DH|
Sheehan|Jason P|JP|

D020785:Central Nervous System Vascular Malformations

stereotactic radiosurgery
radiosurgery
dural arteriovenous fistula
arteriovenous fistula
review
AVM = arteriovenous malformation
CS = cavernous sinus
CVD = cortical venous drainage
DAVF = dural arteriovenous fistula
GKS = Gamma Knife surgery
LINAC = linear accelerator
NCS = noncavernous sinus
SRS = stereotactic radiosurgery
TSS = transverse and sigmoid sinus


Description and comparison of exam wrapper learning strategy use in baccalaureate and associate degree nursing students: A descriptive study.

Abstract:
BACKGROUND
Exam wrapper, a structured self-regulated learning strategy, assists students to review study habits and performance on an exam with the goal of improving future study habits. Little is known about the use of this strategy in nursing students, particularly associate degree students.

OBJECTIVES
To describe and compare demographic characteristics, study habits, reasons for getting content wrong on an exam and future study plans between associate degree and baccalaureate nursing students.

DESIGN
A cross sectional, descriptive comparative study of exam wrapper use in associate degree and baccalaureate nursing students.

SETTINGS
A medium-sized public university and small private college in the northeastern United States.

PARTICIPANTS
A convenience sample 102 prelicensure baccalaureate (n = 63) and associate degree (n = 39) nursing students. Mean age of 21.9 ± 5.6, GPA of 3.46 ± 0.38, 7% male, 57% commuter students, 75% employed an average of 14 ± 11.4 h per week.

METHODS
Data were collected by course faculty during an in-class exam review following a multiple-choice examination. Students completed a demographic form and exam wrapper that assessed pre-exam study habits, reasons for getting items wrong on an exam and future study habits.

RESULTS
Associate degree students had lower GPAs (3.19 vs 3.57, p = .000), were older (27 vs 19.2, p = .000), more often commuted (100% vs 31%, p = .000), were employed (95% vs 65%, p < .001), were more likely to study at home (39.5% vs 13.1%, p = .000) and spent significantly longer on each study activity (p = .000) than baccalaureate students. When comparing reasons for getting a question wrong and intended study habits, baccalaureate and associate degree students did not differ.

CONCLUSIONS
Use of the exam wrapper strategy allows nursing students at all levels of prelicensure education to actively reflect upon their learning with the goal of improving future learning.

Sethares|Kristen A|KA|
Asselin|Marilyn E|ME|
Mahoney|Dianne|D|
Nicotera|Judy|J|
Chung|Joohyun|J|
Schuler|Monika|M|

Exam wrapper
Learning
Associate degree
Nursing students
Self-regulation
Baccalaureate degree
Metacognition


Integrity of serum samples is changed by modified centrifugation conditions.

Abstract: Background Serum samples should be centrifuged for at least 10 min at 1300-2500 × g. Changed centrifugation conditions could compromise sample quality. The objective of this study was to compare the serum quality and turnaround time (TAT) using different centrifugation conditions. Methods The study was done in four different periods (A, B, C and D) at different conditions: for 10, 5 and 7 (A, B and C, respectively) at 2876 × g, and 7 (D) min at 4141 × g. Sample quality was assessed as the proportion of samples with: (a) aspiration errors, (b) H index >0.5 g/L and (c) suppressed reports of potassium (K) due to hemolysis. TAT was calculated for emergency samples. The proportions of samples (a), (b) and (c) were compared according to period A. Results The number of aspiration errors was significantly higher in samples centrifuged at 2876 × g for 5 min (p = 0.021) and remained unchanged when centrifuged for 7 min (p = 0.066 and 0.177, for periods C and D, respectively). In periods B, C and D, the proportion of samples with hemolysis was higher than that in period A (p-values 0.039, 0.009 and 0.042, respectively). TAT differed between all periods (p < 0.001), with the lowest TAT observed for B and D. The lowest number of samples exceeding 60-min TAT was observed in period D (p = 0.011). Conclusions The integrity of serum samples is changed with different centrifugation conditions than those recommended. Our study showed that shorter centrifugation at higher force (7 min at 4141 × g) significantly decreases TAT, with unchanged proportion of samples with aspiration errors.

Miler|Marijana|M|
Nikolac Gabaj|Nora|N|
Culej|Jelena|J|
Unic|Adriana|A|
Vrtaric|Alen|A|
Milevoj Kopcinovic|Lara|L|

centrifugation
sample quality
turnaround time
hemolysis
residual fibrin strands


Atmospheric observation-based estimation of fossil fuel CO2 emissions from regions of central and southern California.

Abstract: Combustion of fossil fuel is the dominant source of greenhouse gas emissions to the atmosphere in California. Here, we describe radiocarbon (14CO2) measurements and atmospheric inverse modeling to estimate fossil fuel CO2 (ffCO2) emissions for 2009-2012 from a site in central California, and for June 2013-May 2014 from two sites in southern California. A priori predicted ffCO2 mixing ratios are computed based on regional atmospheric transport model (WRF-STILT) footprints and an hourly ffCO2 prior emission map (Vulcan 2.2). Regional inversions using observations from the central California site suggest that emissions from the San Francisco Bay Area (SFBA) are higher in winter and lower in summer. Taking all years together, the average of a total of fifteen 3-month inversions from 2009 to 2012 suggests ffCO2 emissions from SFBA were within 6 ± 35% of the a priori estimate for that region, where posterior emission uncertainties are reported as 95% confidence intervals. Results for four 3-month inversions using measurements in Los Angeles South Coast Air Basin (SoCAB) during June 2013-May 2014 suggest that emissions in SoCAB are within 13 ± 28% of the a priori estimate for that region, with marginal detection of any seasonality. While emissions from the SFBA and SoCAB urban regions (containing ~50% of prior emissions from California) are constrained by the observations, emissions from the remaining regions are less constrained, suggesting that additional observations will be valuable to more accurately estimate total ffCO2 emissions from California as a whole.

Cui|Xinguang|X|
Newman|Sally|S|
Xu|Xiaomei|X|
Andrews|Arlyn E|AE|
Miller|John|J|
Lehman|Scott|S|
Jeong|Seongeun|S|
Zhang|Jingsong|J|
Priest|Chad|C|
Campos-Pineda|Mixtli|M|
Gurney|Kevin R|KR|
Graven|Heather|H|
Southon|John|J|
Fischer|Marc L|ML|

Atmospheric inversion
ffco2 emissions
SFBA and SoCAB
Radicocarbon
Seasonal variation
Tower-based measurements


Effect of breast-feeding frequency on hyperbilirubinemia in breast-fed term neonate.

Abstract:
BACKGROUND
Hyperbilirubinemic neonates have significantly less bodyweight gain from nursery discharge to outpatient department (OPD) follow up. We tested the hypothesis that discharge instructions encouraging frequent breast-feeding given in the nursery would increase infant bodyweight gain and decrease the incidence of hyperbilirubinemia.

METHODS
We enrolled consecutively live-born neonates who were discharged from the nursery and who received OPD follow up within the first 2 weeks of birth in 2011. The nursing staff discussed the discharge instructions with the parents at the time of nursery discharge. Parents were asked to fill in a nursing information form to record the frequency of breast-feeding and diaper change per day.

RESULTS
Parents of 98 breast-fed term neonates provided complete nursing information forms. These 98 neonates were classified into two groups according to breast-feeding frequency, namely <8 times/day (63 neonates) and ≥8 times/day (35 neonates). A significant positive correlation between breast-feeding frequency and diaper change frequency per day indicated that the data were highly reliable. The gestational age, Apgar score, birthweight, and bodyweight at nursery discharge and at OPD were similar between the two groups. Neonates who were breast-fed ≥8 times/day had a significantly lower incidence of hyperbilirubinemia.

CONCLUSIONS
Nursery discharge instructions that encouraged mothers to breast-feed their newborns frequently decreased the rate of hyperbilirubinemia in exclusively breast-fed term neonates.

breast-feeding
neonate
discharge instruction
transcutaneous bilirubin


HEALTHCARE-ASSOCIATED INFECTION IN NEUROSURGICAL PATIENTS IN UKRAINE: RESULTS OF A MULTICENTER STUDY (2017-2019).

Abstract:
OBJECTIVE
The aim: To obtain the estimates of the current prevalence of healthcare-associated infection among neurosurgical patients and determine the antimicrobial resistance of responsible pathogens in Ukraine.

PATIENTS AND METHODS
Materials and methods: We performed a retrospective multicenter cohort study was based on surveillance data of HAIs among neurosurgical patients from 2017 to 2019 in 7 regional hospitals. Definitions of HAI were used from the CDC/ NHSN.

RESULTS
Results: Of 9,711 neurosurgical patients, 1,031 (20.9%) HAIs were observed. The most frequently of HAI types were surgical site infection (53.2%), pneumonia (17.3%), urinary tract infection (15.1%) and bloodstream infection (14.4%). The overall prevalence of HAIs was 20.9% within three months and was 12.8% during one month surveillance period. Death during hospitalization was reported in 11.3% of HAI cases. Escherichia coli were most commonly reported, accounting for 24.3% of all organisms, followed by Staphylococcus aureus (15.9%), Enterococcus spp (14.6%), Pseudomonas aeruginosa (13.4%), and Klebsiella pneumoniae (9.8%). Meticillin resistance was 34.6% of S.aureus isolates. Vancomycin resistance was in 7.1% of isolated enterococci. Among the gram-negative bacteria, third-generation cephalosporins resistance was found in 48.5% of K.pneumoniae and in 34.3% of E. coli isolates. Carbapenem resistance was reported in 11.7% of all included Enterobacteriaceae, also highest in K.pneumoniae, and in 32.4% of P.aeruginosa isolates and in 67.2% of Acinetobacter spp. isolates.

CONCLUSION
Conclusions: Healthcare-associated infections are a cause for mortality and morbidity among hospitalized neurosurgical patients. This is due to increase emergence of antimicrobial-resistant pathogens. Routinely collected surveillance data are of great value as a basis for studying the consequences of HAIs.

Salmanov|Aidyn G|AG|
Shchehlov|Dmytro V|DV|
Svyrydiuk|Oleh|O|
Bortnik|Ihor M|IM|
Mamonova|Maryna|M|
Kudelskyi|Yaroslav|Y|
Rzayeva|Farida H|FH|

D000900:Anti-Bacterial Agents
D015331:Cohort Studies
D003428:Cross Infection
D003695:Delivery of Health Care
D024881:Drug Resistance, Bacterial
D004926:Escherichia coli
D006801:Humans
D012189:Retrospective Studies
D014455:Ukraine

healthcare-associated infection
prevalence
antimicrobial resistance
mortality
Neurosurgery


Putting the NHS England on trial: uncertainty-as-power, evidence and the controversy of PrEP in England.

Abstract: Pre-exposure prophylaxis (PrEP) (Truvada) is a medication which if taken correctly is almost entirely effective in preventing HIV infection. In regions and countries where it has been widely taken up, HIV seroconversion rates have significantly decreased. Alongside testing and treatment, it offers the very real prospect of ending HIV infections. However, in England, commissioning it has (and still is) a controversial process, where NHS England has repeatedly raised supposed 'uncertainties', first legal and then scientific. The same has not happened in Scotland, where PrEP was commissioned to anyone who needed it in April 2017. This article presents a close reading of the IMPACT trial protocol, which we conclude cannot answer the questions it sets out to answer. We then suggest that the uncertainties the trial claims to address are in fact a tool of power which is deployed to strategically ration healthcare; introduce uncertainty about commissioning PrEP; and shift the boundary between individual responsibilities and state responsibilities for public health and HIV prevention. We conclude that all the above constitute an unethical use of clinical trial rhetoric, systematically discriminate against minority and vulnerable groups, and ration healthcare for those who most need it. As such, we call on all academics, clinicians and activists to resist further unethical misuses of clinical trial rhetoric.

public health
HIV/AIDS
health policy
medical ethics/bioethics
sexual medicine


The effect of anxiety on cognition in older adult inpatients with depression: results from a multicenter observational study.

Abstract: Late-life depression is associated with reduced cognitive function beyond normal age-related cognitive deficits. As comorbid anxiety frequently occur in late-life depression, this study aimed to examine the association between anxiety symptoms and cognitive function among older inpatients treated for depression. We hypothesized that there would be an overall additive effect of comorbid anxiety symptoms on dysfunction across cognitive domains. The study included 142 patients treated for late-life depression in hospital, enrolled in the Prognosis of Depression in the Elderly study. Anxiety symptoms were measured at admission using the anxiety subscale of the Hospital Anxiety and Depression Scale. Patients completed cognitive tasks at admission and discharge. Linear mixed and generalized linear mixed models were estimated to investigate the effect of anxiety, on continuous and categorical cognitive scores, respectively, while controlling for depression. Anxiety severity at admission was not associated with performance in any of the cognitive domains. Patients with more symptoms of anxiety at admission demonstrated a significant improvement in immediate recall during the hospital stay. Patients with a score above cutoff indicating clinically significant symptoms on the anxiety subscale performed better on general cognitive function, as measured by the Mini Mental Status Examination at admission, than those below cutoff for anxiety. In conclusion, comorbid anxiety symptoms had no additive effect on cognitive dysfunction in late-life depression in our sample of inpatients.

Martinussen|Liva Jenny|LJ|
Šaltytė Benth|Jūratė|J|
Almdahl|Ina Selseth|IS|
Borza|Tom|T|
Selbæk|Geir|G|
Mcpherson|Bodil|B|
Korsnes|Maria Stylianou|MS|

Anxiety
Cognition
Older adults
Late-life depression
Cognitive function
Clinical psychology
Psychiatry
Seniors


Prenatal diagnosis of concomitant distal 5q duplication and terminal 10q deletion in a fetus with intrauterine growth restriction, congenital diaphragmatic hernia and congenital heart defects.

Abstract:
OBJECTIVE
We present prenatal diagnosis of concomitant distal 5q duplication and terminal 10q deletion in a fetus with intrauterine growth restriction (IUGR), congenital diaphragmatic hernia (CDH) and congenital heart defects (CHD).

CASE REPORT
A 34-year-old, gravida 4, para 2, woman was referred for amniocentesis at 21 weeks of gestation because of advanced maternal age and IUGR. There was no congenital malformation in the family. Amniocentesis revealed a derivative chromosome 10 with an additional maternal on the terminal region of 10q. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from the cultured amniocytes revealed a result of arr 5q31.3q35.5 (142, 548, 354-180,696,806) × 3.0, arr 10q26.3 (132, 932, 808-135,434,178) × 1.0 [GRCh37 (hg19)] with a 2.50-Mb deletion of 10q26.3 encompassing 19 [Online Mendelian Inheritance in Man (OMIM)] genes and a 38.15-Mb duplication of 5q31.3-q35.5 encompassing 195 OMIM genes including four CDH candidate genes of NDST1, ADAM19, NSD1 and MAML1. The mother was found to have a karyotype of 46,XX,t(5; 10) (q31.3; q26.3). Therefore, the fetal karyotype was 46,XX,der(10)t(5; 10)(q31.3; q26.3)mat. Prenatal ultrasound showed IUGR, right CDH, transposition of great artery, double outlet of right ventricle and right atrial isomerism. The pregnancy was terminated, and a malformed fetus was delivered with facial dysmorphism.

CONCLUSION
Fetuses with concomitant distal 5q duplication and terminal 10q deletion may present IUGR, CDH and CHD on prenatal ultrasound.

Chen|Chih-Ping|CP| Huang|Jian-Pei|JP| Chen|Shin-Wen|SW| Chern|Schu-Rern|SR| Wu|Peih-Shan|PS| Wu|Fang-Tzu|FT| Chen|Wen-Lin|WL| Chen|Li-Feng|LF| Wang|Wayseen|W|

5q duplication
10q deletion
Intrauterine growth restriction
Congenital diaphragmatic hernia
Congenital heart defects


Effectiveness and safety of eribulin in Japanese patients with HER2-negative, advanced breast cancer: a 2-year post-marketing observational study in a real-world setting.

Abstract: Background Data on eribulin as the first- or second-line treatment in a clinical setting, especially the overall survival (OS) of patients, are scarce. Therefore, we assessed the effectiveness and safety of eribulin as the first-, second-, and third- or later-line treatments in patients with human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in Japan. Methods This multicenter, prospective, post-marketing, observational study enrolled patients from September 2014 to February 2016 in Japan and followed them for 2 years. Patients were categorized by eribulin use into the first-, second-, and third- or later-line treatment groups. Results Of 651 registered patients, 637 patients were included in the safety and effectiveness analysis. In all, first-, second-, and third or later-line treatment groups, median OS (95% confidence interval) were 15.6 (13.8-17.6), 22.8 (17.3-31.0), 16.3 (12.4-19.9), and 12.6 (11.2-15.1) months and time to treatment failure (TTF) (95% confidence interval) were 4.2 (3.7-4.4), 5.2 (3.7-5.9), 4.2 (3.7-5.1), and 3.8 (3.5-4.2) months, respectively. Prolonged TTF was associated with complications of diabetes and the development of peripheral neuropathy after eribulin treatment, according to multivariate Cox regression analysis. Grade ≥ 3 adverse drug reactions (ADRs) were reported in 61.7% of the patients. Neutropenia (49.5%) was the most common grade ≥ 3 ADR in all groups. Conclusions The effectiveness and safety results of eribulin as the first- or second-line treatment were favorable. Thus, these suggest eribulin may be a first-line treatment candidate for patients with HER2-negative advanced breast cancer in Japan.

Eribulin
Overall survival
Japan
Post-marketing study


Topical immunotherapy in combination with anthralin in the treatment of refractory alopecia areata.

Abstract:
BACKGROUND
Treatment is often challenging in patients with alopecia areata. We often try topical immunotherapy to treat alopecia areata in Japan. Anthralin is sometimes used in other countries.

OBJECTIVES
The aim of this study was to examine effectiveness of combination therapy with both topical immunotherapy with squaric acid dibutylester or diphenylcyclopropenone and anthralin in the treatment of refractory alopecia areata.

METHODS
We treat four patients with refractory alopecia areata by topical immunotherapy and anthralin. Two patients had alopecia areata multilocularis and the other two patients had alopecia totalis. The entire scalp was treated with weekly application of squaric acid dibutylester or diphenylcyclopropenone and daily 0.5% anthralin ointment. Patients were followed up weekly, and adverse effects were recorded.

RESULTS
One patient with multifocal patches of alopecia areata got complete hair regrowth at week 30, the other patient with multifocal patches of alopecia areata turned for the worse at week 30 and recovered at week 52. Hair regrowth was not seen in the other two patients with alopecia totalis. Localized pruritis and hyperpigmentation of the scalp were seen in two patients.

CONCLUSIONS
To treat alopecia areata unresponsive to topical immunotherapy alone, topical immunotherapy in combination with anthralin is worth a try.

DPCP
SADBE
contact immunotherapy
intractable alopecia
recalcitrant alopecia


Associations between PM1 exposure and daily emergency department visits in 19 hospitals, Beijing.

Abstract: Although the adverse health effects caused by PM2.5 (particulate matter (PM) with an aerodynamic diameter <2.5 μm) and PM10 (PM with an aerodynamic diameter <10 μm) have been examined in numeric studies, far less scientific evidence is available for PM with an aerodynamic diameter <1 μm (PM1). We performed a time series analysis to elucidate the associations between PM1 exposure and emergency department visits (EDVs) in 19 hospitals within Beijing. During the study period from January 2016 to December 2017, the average PM1 (mean ± standard deviation) was determined to be 39 ± 39 μg/m3, which was approximately 36% lower than that of 61 ± 56 μg/m3 for PM2.5. Results based on meta-analysis suggest that non-accidental and respiratory EDVs increased by 0.47% (95% confidence interval, CI: 0.35, 0.59%) and 0.59% (95%CI: 0.38, 0.8%) per 10 μg/m3 uptick in PM1 exposure. By comparison, the magnitude downgraded to 0.27% (95%CI: 0.15, 0.39%) in non-accidental and 0.32% (95%CI: 0.18, 0.47%) in respiratory EDVs for PM2.5 exposure, indicating that PMs of a smaller size may be a higher risk factor for EDVs. No significant differences in PM-associated EDV effects were noted between males and females, while stratified analysis by age and season illustrated that stronger effects were found for a warm season and young population. Our analysis reinforces the notion that PM1 exhibited a higher risk for EDVs, suggesting more efforts may be required to mitigate PM1 pollution.

Wang|Hao|H| Lu|Feng|F| Guo|Moning|M| Fan|Wenhong|W| Ji|Wei|W| Dong|Zhaomin|Z|

Association
Emergency department visits
Beijing
PM(1)
Respiratory diseases


Tertiary lymphoid organs in the inflammatory myopathy associated with PD-1 inhibitors.

Abstract:
BACKGROUND
Programmed cell death 1 inhibitors have revolutionized therapy for cancer by their outstanding effectiveness. However, they may cause adverse effects, among which inflammatory myopathy is one of the most disabling. To elucidate its mechanism, we analysed muscle biopsies and compared them with other inflammatory myopathies.

METHODS
Muscle biopsies from three patients with inflammatory myopathy after treatment with PD-1 inhibitors for cancer were subjected to immunohistochemical and ultrastructural analyses to localize CD8+ cytotoxic cells and markers of lymphoid follicles. For comparison, two cases of polymyositis and one of juvenile dermatomyositis were examined.

RESULTS
Nearly identical pathological features were observed in the three cases. In the island-like foci of inflammation, muscle fibers were undergoing degeneration. CD8+ cytotoxic T cells, macrophages, CD4+ cells, and B cells were observed in the foci. CD8+ cells were seen outside and inside the basal lamina of non-necrotic muscle fibers. Lymphoid follicle-like structures with CD21+ follicular dendritic cells were present. The blood vessels in the foci showed features consistent with the high endothelial venules, on which their markers, PNAd and CCL21, were expressed. In polymyositis, blood vessels stained only faintly for PNAd and CCL21, while in juvenile dermatomyositis, in which tertiary lymphoid follicle-like structure was reported in the past, they stained positively.

CONCLUSIONS
In inflammatory myopathy associated with PD-1 inhibitors, CD8+ cells appear to predominantly destruct muscle fibers. The presence of lymphoid follicle-like structures and expression of PNAd and CCL21 on the endothelial cells suggest the tertiary lymphoid organs are formed, and involved in the leakage of lymphocytes. Thus, in the three cases examined, formation of the tertiary lymphoid organs is likely to play an important role in genesis of the PD-1 myopathy.

Matsubara|Shiro|S|0000-0002-2519-5700 Seki|Morinobu|M| Suzuki|Shigeaki|S| Komori|Takashi|T| Takamori|Mikio|M|

D061026:Programmed Cell Death 1 Receptor

Tertiary lymphoid organ
Inflammatory myopathy
PD-1 inhibitor
Adverse effect
Cytotoxic T cell
High endothelial venule


The mediating role of general self-efficacy in the association between perceived social support and oral health-related quality of life after initial periodontal therapy.

Abstract:
BACKGROUND
Although initial periodontal therapy can ease some physical and psychological discomforts from periodontitis and improve patients' oral health-related quality of life (OHRQoL), it is also vital to find positive resources from psychological and social aspects to promote the overall OHRQoL. This study aims to explore the associations of perceived social support (PSS) and general self-efficacy with OHRQoL and the mediating role of general self-efficacy in PSS-OHRQoL association after initial periodontal therapy.

METHODS
A prospective case series study was conducted among consecutive outpatients with chronic periodontitis during the period of July 2014-April 2015. A total of 145 eligible patients responded to OHRQoL questionnaire and periodontal examination at baseline. About 4 to 5 weeks after initial periodontal therapy, 120 patients completed the second OHRQoL measurement and periodontal examination, along with PSS and general self-efficacy measurement. The Wilcoxon matched-pairs signed-rank test was used to determine the difference between baseline and post-treatment OHRQoL scores and periodontal parameters. Hierarchical linear regression analysis was used to explore the associations of PSS and general self-efficacy with post-treatment OHRQoL after adjusting for some demographic and periodontal variables. Asymptotic and resampling strategies were performed to explore the mediating role of general self-efficacy.

RESULTS
Initial periodontal therapy resulted in a significant improvement in the mean total score and all domains of OHRQoL and all periodontal parameters measured. In hierarchical linear regression analysis, clinical attachment loss (CAL) was significantly and positively associated with post-treatment OHRQoL score (β = 0.265, p < 0.01), while PSS (β = -0.303, p < 0.01) and general self-efficacy (β = -0.221, p < 0.01) were significantly and negatively associated with post-treatment OHRQL score, respectively. A significant mediating role of general self-efficacy (a*b = -0.139, BCa 95 % CI: -0.298, -0.011) in the association between PSS and post-treatment OHRQoL was revealed, and the proportion of the mediating role of general self-efficacy was 31.4 %.

CONCLUSIONS
Initial periodontal therapy could significantly improve all aspects of OHRQoL. PSS and general self-efficacy could be the positive resources for improving OHRQoL after initial periodontal therapy among patients with periodontitis. General self-efficacy partly mediated the association between PSS and post-treatment OHRQoL.

Miao|Lei|L| Feng|Jingwen|J| Wu|Liuzhong|L| Zhang|Shuwei|S| Ge|Ziming|Z| Pan|Yaping|Y|

D006801:Humans
D009909:Oral Health
D010510:Periodontal Diseases
D011446:Prospective Studies
D011788:Quality of Life
D020377:Self Efficacy
D012944:Social Support

General self-efficacy
Perceived social support
Oral health-related quality of life
Initial periodontal therapy
Periodontitis


From chaos to control - experiences of healthcare workers during the early phase of the COVID-19 pandemic: a focus group study.

Abstract:
BACKGROUND
The Coronavirus disease 2019 (COVID-19) pandemic has caused overwhelming challenges to healthcare systems worldwide. Healthcare workers (HCWs) have faced particular challenges: being exposed to the coronavirus SARS-CoV-2 and caring for patients having a new and potentially life-threatening disease. The aim of this study was to explore how HCWs in the Swedish healthcare system perceived their work situation during the first phase of the COVID-19 pandemic in 2020.

METHODS
Focus group discussions and interviews with HCWs were performed from June to October 2020 in one Swedish healthcare region. A purposeful sampling approach was used to select a variety of professions (physicians, nurses, nurse aides and cleaners) and workplaces (hospital inpatient wards, emergency department, nursing home and home care service). Qualitative content analysis was used for data analysis.

RESULTS
In total, 51 HCWs participated in eight focus group discussions and one HCW participated in an individual interview. The content analysis identified two main categories: 'Concerns about the risk of infection and transmission of infection to others', and 'Transition from chaos to managing in a new and challenging work situation'. The findings revealed how HCWs perceived working conditions, including experiences of fear for personal health, confusion and uncertainty regarding personal protective equipment and infection prevention and control (PPE/IPC), and fear of infecting others. Both fearful and appreciating attitudes were achieved from the surrounding community. Helpful strategies for transition from chaos to control were lifted i.e. present and supportive leadership, and finding comfort and strength in the working team. Both helplessness and meaningfulness were described when caring for COVID-19 patients.

CONCLUSIONS
This study provides unique insights into HCWs experiences of an extremely challenging work situation during the first phase of the COVID-19 pandemic, including feelings of stress and insecurity in a chaotic and hazardous working environment. But there is also mitigation of these challenges and even positive experiences including feelings of safety and meaningfulness. To enhance safety among HCWs in healthcare crises such as the COVID-19 pandemic, the findings highlight the importance of avoiding confusion about PPE/IPC, having a supportive healthcare leadership and ensuring accurate information provision about virus transmission to the public.

Coronavirus disease 2019
Health personnel
Infection control
Mental health
Occupational health
Patient care
Qualitative research


Quality Metrics and Systems Transformation: Are We Advancing Alcohol and Drug Screening in Primary Care?

Abstract:
OBJECTIVE
To examine the influence of Oregon's coordinated care organizations (CCOs) and pay-for-performance incentive model on completion of screening and brief intervention (SBI) and utilization of substance use disorder (SUD) treatment services.

DATA SOURCES/STUDY SETTING
Secondary analysis of Medicaid encounter data from 2012 to 2015 and semiannual qualitative interviews with stakeholders in CCOs.

STUDY DESIGN
Longitudinal mixed-methods design with simultaneous data collection with equal importance.

DATA COLLECTION/EXTRACTION METHODS
Qualitative interviews were recorded, transcribed, and coded in ATLAS.ti. Quantitative data included Medicaid encounters 30 months prior to CCO implementation, a 6-month transition period, and 30 months following CCO implementation. Data were aggregated by half-year with analyses restricted to Medicaid recipients 18-64 years of age enrolled in a CCO, not eligible for Medicare coverage or Medicaid expansion.

PRINCIPAL FINDINGS
Quantitative analysis documented a significant increase in SBI rates coinciding with CCO implementation (0.1 to 4.6 percent). Completed SBI was not associated with increased initiation in treatment for SUD diagnoses. Qualitative analysis highlighted importance of aligning incentives, workflow redesign, and leadership to facilitate statewide SBI.

CONCLUSIONS
Results provide modest support for use of a performance metric to expand SBI in primary care. Future research should examine health reform efforts that increase initiation and engagement in SUD treatment.

Rieckmann|Traci|T|
Renfro|Stephanie|S|
McCarty|Dennis|D|
Baker|Robin|R|
McConnell|K John|KJ|

primary care
Evidence-based practice
state health policies
substance abuse


Cellulose nanofibers coated with silver nanoparticles as a flexible nanocomposite for measurement of flusilazole residues in Oolong tea by surface-enhanced Raman spectroscopy.

Abstract: Cellulose nanofibers (CNF) coated with inorganic nanoparticles are novel hybrid nanocomposites that have great potential in various areas including agriculture and food science. The objectives of this study were to synthesize nanocomposites consisted of CNF coated with silver nanoparticles (AgNPs), which can be used as a surface-enhanced Raman spectroscopy (SERS) platform for measuring pesticides in Oolong tea. CNF were coated with AgNPs to form uniform CNF-AgNP nanocomposites that were investigated by transmission electron microscopy. Three-dimensional and porous CNF structures were loaded with AgNPs with an average size of 41 nm. CNF-AgNP substrates were applied in characterization and measurement of flusilazole in Oolong tea samples by SERS. A detection limit of 0.5 mg/kg for flusilazole was obtained based on partial least squares (PLS) regression analysis. These results indicate that CNF-AgNP nanocomposites combined with SERS is an accurate, sensitive, and efficient technique for identification and quantification of pesticide residues in Oolong tea.

Chen|Xi|X| Lin|Hetong|H| Xu|Taotao|T| Lai|Keqiang|K| Han|Xue|X| Lin|Mengshi|M|

Surface-enhanced Raman spectroscopy (SERS)


Multi-Objective Optimization of Friction Stir Welding Process Parameters of AA6061-T6 and AA7075-T6 Using a Biogeography Based Optimization Algorithm.

Abstract: The development of Friction Stir Welding (FSW) has provided an alternative approach for producing high-quality welds, in a fast and reliable manner. This study focuses on the mechanical properties of the dissimilar friction stir welding of AA6061-T6 and AA7075-T6 aluminum alloys. The FSW process parameters such as tool rotational speed, tool traverse speed, tilt angle, and tool offset influence the mechanical properties of the friction stir welded joints significantly. A mathematical regression model is developed to determine the empirical relationship between the FSW process parameters and mechanical properties, and the results are validated. In order to obtain the optimal values of process parameters that simultaneously optimize the ultimate tensile strength, elongation, and minimum hardness in the heat affected zone (HAZ), a metaheuristic, multi objective algorithm based on biogeography based optimization is proposed. The Pareto optimal frontiers for triple and dual objective functions are obtained and the best optimal solution is selected through using two different decision making techniques, technique for order of preference by similarity to ideal solution (TOPSIS) and Shannon's entropy.

Tamjidy|Mehran|M|
Baharudin|B T Hang Tuah|BTHT|
Paslar|Shahla|S|
Matori|Khamirul Amin|KA|
Sulaiman|Shamsuddin|S|
Fadaeifard|Firouz|F|

multi-objective biogeography based optimization (MOBBO)


Mapping Electrical Impedance Spectra of the Healthy Oral Mucosa: a Pilot Study.

Abstract:
OBJECTIVE
Electrical impedance is the resistance to the electric current flow through a tissue and depends on the tissue's structure and chemical composition. The aim of this study was to map electrical impedance spectra for each region of the healthy oral mucosa.

MATERIALS AND METHODS
Electrical impedance was measured in 30 participants with healthy oral mucosa. Measurements were performed in 14 points on the right and the left side of the oral cavity, and repeated after 7 and 14 days respectively.

RESULTS
The lowest values were measured on the tongue dorsum and the highest values were measured on the hard palate. No significant differences were found between the right and the left side. Significantly higher values were found in females on the upper labial mucosa, tongue dorsum and the ventral tongue. Significant difference between smokers and non-smokers on the lower labial mucosa and floor of the mouth was found. Electrical impedance was negatively correlated with salivary flow on the upper labial mucosa, hard palate, tongue dorsum and sublingual mucosa. Higher variability of measurements was found at low frequencies.

CONCLUSIONS
Electrical impedance mostly depends on the degree of mucosal keratinization. Demographic and clinical factors probably affect its values. Further studies with bigger number of participants are required.

Richter|Ivica|I|
Alajbeg|Ivan|I|
Boras|Vanja Vučićević|VV|
Rogulj|Ana Andabak|AA|
Brailo|Vlaho|V|

electrical impedance spectrum measurement


Right sensory-motor functional networks subserve action observation therapy in aphasia.

Abstract: Recent studies have shown that the systematic and repetitive observation of actions belonging to the experiential human motor repertoire without verbal facilitation enhances the recovery of verbs in non fluent aphasia. However, it is still an open question whether this approach extends its efficacy also on discourse productivity by improving the retrieval of other linguistic units (i.e. nouns, sentences, content words). Moreover, nothing is known regarding the neural substrates which support the language recovery process due to action observation treatment.In the present study, ten non fluent aphasics were presented with two videoclips (real everyday life context vs. familiar pantomimed context), each video for six consecutive weeks (Monday to Friday, weekend off). During the treatment, they were asked to observe each video and to describe it without verbal facilitation from the therapist. In all patients, language measures were collected before and at the end of treatment. Before and after each treatment condition (real vs. pantomimed context), each subject underwent a resting state fMRI. After the treatment, significant changes in functional connectivity were found in right sensory-motor networks which were accompanied by a significant improvement for the different linguistic units in the real context condition. On the contrary, the language recovery obtained in the pantomimed context did not match any functional modification. The evidence for a recruitment of the sensory-motor cortices during the observation of actions embedded in real context suggests to potentially enhance language recovery in non fluent aphasia through a simulation process related to the sensory-motor properties of actions.

Gili|Tommaso|T|
Fiori|Valentina|V|
De Pasquale|Giada|G|
Sabatini|Umberto|U|
Caltagirone|Carlo|C|
Marangolo|Paola|P|

Action observation
Sensory-motor network
Aphasia therapy
Embodied theory
Mirror system


Implications of mercury concentrations in umbilical cord tissue in relation to maternal hair segments as biomarkers for prenatal exposure to methylmercury.

Abstract: In this study, we investigated how mercury (Hg) concentrations in umbilical cord tissue are correlated with those in biomarkers for prenatal exposure to methylmercury (MeHg). Total Hg (T-Hg) concentrations were measured in 54 mother-child paired samples of maternal blood, umbilical cord tissue, cord blood, and maternal hair segments (1-cm incremental segments from the scalp) collected at parturition. MeHg concentrations were also measured in the cord tissue. Median T-Hg and MeHg concentrations in cord tissue on a dry-weight basis (d.w.) were 62.2ng/g and 56.7ng/g, respectively. Proportions of MeHg to T-Hg were approximately 95%. Both T-Hg and MeHg in cord tissue (d.w.) showed better correlations with T-Hg in cord blood than did T-Hg in cord tissue on a wet-weight basis (w.w.). Median T-Hg concentrations in maternal blood, cord blood, and maternal hair (0-1cm from the scalp) were 3.79ng/g, 7.26ng/g, and 1.35 μg/g, respectively. Median T-Hg concentration in cord blood was 1.92 times higher than that in maternal blood. T-Hg in cord tissue (d.w.) showed a strong correlation with that in cord blood (r=0.912, p<0.01). Among the hair segments, T-Hg in cord tissue (d.w.) showed the strongest correlation (r=0.854, p<0.01) with that in maternal hair at 0-1cm from the scalp, reflecting growth for approximately 1 month before parturition. Based on the present results, T-Hg and MeHg concentrations in cord tissue may be useful biomarkers for prenatal MeHg exposure of the fetus, especially reflecting the maternal MeHg body burden during late gestation. The conversion factors for T-Hg and MeHg concentrations in cord tissue (d.w.) to T-Hg concentrations in maternal hair (0-1cm from the scalp) were calculated to be 22.37 and 24.09, respectively. This information will be useful for evaluating maternal MeHg exposure levels in retrospective studies using preserved umbilical cord tissue.

Sakamoto|Mineshi|M|
Murata|Katsuyuki|K|
Domingo|José L|JL|
Yamamoto|Megumi|M|
Oliveira|Ricardo B|RB|
Kawakami|Shoichi|S|
Nakamura|Masaaki|M|

Mercury
Umbilical cord tissue
Maternal hair segments
Methylmercury
Maternal blood
Cord blood


Associations Between Injury of the Parieto-Insular Vestibular Cortex and Changes in Motor Function According to the Recovery Process: Use of Diffusion Tensor Imaging.

Abstract: Background and Purpose: Parieto-insular vestibular cortex (PIVC) injury can cause symptoms such as abnormal gait and affects the integration and processing of sensory inputs contributing to self-motion perception. Therefore, this study investigated the association of the vestibular pathway in the gait and motor function recovery process in patients with PIVC injury using diffusion tensor imaging (DTI). Methods: We recruited 28 patients with stroke with only PIVC injury and reconstructed the PIVC using a 1.5-T scanner for DTI. Fractional anisotropy (FA), mean diffusivity (MD), and tract volume were measured. The functional ambulatory category (FAC) test was conducted, and motricity index (MI) score was determined. These were conducted and determined at the start (phase 1), end of rehabilitation (phase 2), and during the follow-up 6 months after onset. Results: Although the tract volume of PIVC showed a decrease in subgroup A, all of DTI parameters were not different between two subgroups in affected side (p > 0.05). The results of MI and FAC were significantly different according to the recovery process (p < 0.05). In addition, FA of the PIVC showed a positive correlation with FAC in phase 2 of the recovery process on the affected side. On the unaffected side, FA of the PIVC showed a significant negative correlation with MI in all processes (p < 0.05). Conclusion: The degree of projection pathways to PIVC injury at onset time seems to be related to early restoration of gait function. Moreover, we believe that early detection of the projection pathway for PIVC injury using DTI would be helpful in the clinical evaluation and prediction of the prognosis of patients with PIVC injury.

Park|Seo Yoon|SY|
Yeo|Sang Seok|SS|
Jang|Sung Ho|SH|
Cho|In Hee|IH|
Oh|Seunghue|S|

parieto-insular vestibular cortex (PIVC)

diffusion tensor imaging-fiber tractography


Open shoulder stabilization: current trends and 1-year postoperative complications.

Abstract:
Background
Shoulder instability is commonly treated by arthroscopic stabilization. However, open stabilization procedures remain important in management of complex instability. Despite continued use of these procedures, the relative frequency of related complications remains poorly described. This study investigates current trends in open shoulder stabilization and characterizes major postoperative complications.

Methods
PearlDiver, a national insurance database of orthopedic patients, was used to identify open shoulder stabilization procedures from 2007 to 2010. Current Procedural Terminology codes for 4 procedures-Bankart repair, coracoid transfer, and anterior and posterior glenoid bone grafting-were used to track procedural trends. The 1-year postoperative complications were identified and categorized into 5 groups: dislocation treated with closed reduction, closed manipulation under anesthesia, reoperation with arthroscopy, reoperation with open surgery, and others. χ 2 analysis determined statistical significance.

Results
There were 2678 open shoulder stabilization procedures performed, with a 1-year complication rate of 12.3%. Relative proportion of open Bankart repairs decreased (82.5% to 69.8%), whereas proportion of coracoid transfers increased (7.7% to 19%). Posterior glenoid bone grafting had the highest complication rate (20.7%). Rate of total complications was 9.8% in patients 10-24 years, 13.6% in patients 25-54 years, and 25.9% in patients >55 years.

Conclusions
Based on our patient database sample, a significant decline in the relative use of open Bankart repair was observed. Our analysis indicates that the use of bone transfer procedures was correlated with significantly higher reoperation rates than open Bankart repair, particularly in the older patient cohort. Further studies comparing open stabilization procedures with contemporary arthroscopic techniques are indicated.

Kowalski|Tomasz J|TJ|
Khan|Adam Z|AZ|
Cohen|Jeremiah R|JR|
Lord|Elizabeth L|EL|
Ishmael|Chad|C|
Soohoo|Nelson F|NF|
McAllister|David R|DR|
Gulotta|Lawrence V|LV|
Wang|Jeffrey C|JC|
Petrigliano|Frank A|FA|

Postoperative complications
Shoulder instability
Bankart repair
Glenoid bone graft
Coracoid process transfer
Surgical trends


Targeting PSD95/nNOS by ZL006 alleviates social isolation-induced heightened attack behavior in mice.

Abstract:
RATIONALE
Deregulated attack behaviors have devastating social consequences; however, satisfactory clinical management for the behavior is still an unmet need so far. Social isolation (SI) has been common during the COVID-19 pandemic and may have detrimental effects on mental health, including eliciting heightened attack behavior.

OBJECTIVES
This study aims to explore whether injection of ZL006 can alleviate SI-induced escalation of attack behavior in mice.

METHODS
Pharmacological tools, biochemical methods, and behavioral tests were used to explore the potential therapeutic effects of ZL006 targeting postsynaptic density 95 (PSD95)/neuronal nitric oxide synthase (nNOS) pathway on escalation of attack behavior induced by SI in mice.

RESULTS
ZL006 mitigated SI-induced escalated attack behaviors and elevated nitric oxide (NO) level in the cortex of the SI mice. The beneficial effects of ZL006 lasted for at least 72 h after a single injection of ZL006. Potentiation of NO levels by L-arginine blocked the effects of ZL006. Moreover, a sub-effective dose of 7-NI in combination with a sub-effective dose of ZL006 decreased both SI-induced escalated attack behaviors and NO levels in mice subjected to SI.

CONCLUSIONS
Our study highlights the importance of the PSD95/nNOS pathway in mediating SI-induced escalation of attack behavior. ZL006 may be a promising therapeutic strategy for treating aggressive behaviors.

ZL006
Social isolation (SI)
Nitric oxide (NO)
Neuronal nitric oxide synthase (nNOS)
Postsynaptic density 95 (PSD95)
Resident–intruder test


The great 2012 Arctic Ocean summer cyclone enhanced biological productivity on the shelves.

Abstract: [1] A coupled biophysical model is used to examine the impact of the great Arctic cyclone of early August 2012 on the marine planktonic ecosystem in the Pacific sector of the Arctic Ocean (PSA). Model results indicate that the cyclone influences the marine planktonic ecosystem by enhancing productivity on the shelves of the Chukchi, East Siberian, and Laptev seas during the storm. Although the cyclone's passage in the PSA lasted only a few days, the simulated biological effects on the shelves last 1 month or longer. At some locations on the shelves, primary productivity (PP) increases by up to 90% and phytoplankton biomass by up to 40% in the wake of the cyclone. The increase in zooplankton biomass is up to 18% on 31 August and remains 10% on 15 September, more than 1 month after the storm. In the central PSA, however, model simulations indicate a decrease in PP and plankton biomass. The biological gain on the shelves and loss in the central PSA are linked to two factors. (1) The cyclone enhances mixing in the upper ocean, which increases nutrient availability in the surface waters of the shelves; enhanced mixing in the central PSA does not increase productivity because nutrients there are mostly depleted through summer draw down by the time of the cyclone's passage. (2) The cyclone also induces divergence, resulting from the cyclone's low-pressure system that drives cyclonic sea ice and upper ocean circulation, which transports more plankton biomass onto the shelves from the central PSA. The simulated biological gain on the shelves is greater than the loss in the central PSA, and therefore, the production on average over the entire PSA is increased by the cyclone. Because the gain on the shelves is offset by the loss in the central PSA, the average increase over the entire PSA is moderate and lasts only about 10 days. The generally positive impact of cyclones on the marine ecosystem in the Arctic, particularly on the shelves, is likely to grow with increasing summer cyclone activity if the Arctic continues to warm and the ice cover continues to shrink.

Zhang|Jinlun|J|
Ashjian|Carin|C|
Campbell|Robert|R|
Hill|Victoria|V|
Spitz|Yvette H|YH|
Steele|Michael|M|

arctic ocean
cyclone effects on biology
ocean mixing


Short-Term High- and Moderate-Intensity Training Modifies Inflammatory and Metabolic Factors in Response to Acute Exercise.

Abstract: Purpose: To compare the acute and chronic effects of high intensity intermittent training (HIIT) and steady state training (SST) on the metabolic profile and inflammatory response in physically active men. Methods: Thirty recreationally active men were randomly allocated to a control group (n = 10), HIIT group (n = 10), or SST group (n = 10). For 5 weeks, three times per week, subjects performed HIIT (5 km 1-min at 100% of maximal aerobic speed interspersed by 1-min passive recovery) or SST (5 km at 70% of maximal aerobic speed) while the control group did not perform training. Blood samples were collected at fasting (~12 h), pre-exercise, immediately post, and 60 min post-acute exercise session (pre- and post-5 weeks training). Blood samples were analyzed for glucose, non-ester fatty acid (NEFA), and cytokine (IL-6, IL-10, and TNF-α) levels through a three-way analysis (group, period, and moment of measurement) with repeated measures in the second and third factors. Results: The results showed an effect of moment of measurement (acute session) with greater values to TNF-α and glucose immediately post the exercise when compared to pre exercise session, independently of group or training period. For IL-6 there was an interaction effect for group and moment of measurement (acute session) the increase occurred immediately post-exercise session and post-60 min in the HIIT group while in the SST the increase was observed only 60 min post, independently of training period. For IL-10, there was an interaction for training period (pre- and post-training) and moment of measurement (acute session), in which in pre-training, pre-exercise values were lower than immediately and 60 min post-exercise, in post-training period pre-exercise values were lower than immediately post-exercise and immediately post-exercise lower than 60 min post, it was also observed that values immediately post-exercise were lower pre- than post-training, being all results independently of intensity (group). Conclusion: Our main result point to an interaction (acute and chronic) for IL-10 showing attenuation post-training period independent of exercise intensity.

Lira|Fabio Santos|FS|
Dos Santos|Thaislaine|T|
Caldeira|Renan Santos|RS|
Inoue|Daniela S|DS|
Panissa|Valéria L G|VLG|
Cabral-Santos|Carolina|C|
Campos|Eduardo Z|EZ|
Rodrigues|Bruno|B|
Monteiro|Paula A|PA|

metabolism exercise cytokines IL-6 TNF-α


Functional annotation and comparative modeling of ligninolytic enzymes from Trametes villosa (SW.) Kreisel for biotechnological applications.

Abstract: Functional annotation of Trametes villosa genome was performed to search Class II peroxidase proteins in this white-rot fungus, which can be valuable for several biotechnological processes. After sequence identification and manual curation, five proteins were selected to build 3 D models by comparative modeling. Analysis of sequential and structural sequences from selected targets revealed the presence of two putative Lignin Peroxidase and three putative Manganese Peroxidase on this fungal genome. All 3 D models had a similar folding pattern from selected 3 D structure templates. After minimization and validation steps, the best 3 D models were subjected to docking studies and molecular dynamics to identify structural requirements and the interactions required for molecular recognition. Two reliable 3 D models of Class II peroxidases, with typical catalytic site and architecture, and its protein sequences are indicated to recombinant production in biotechnological applications, such as bioenergy.Communicated by Ramaswamy H. Sarma.

comparative modeling
White-rot fungus
lignin peroxidase
manganese peroxidase
3D structure
in silico analysis


Heterogeneous estrogen receptor expression in circulating tumor cells suggests diverse mechanisms of fulvestrant resistance.

Abstract: Fulvestrant is a dose dependent selective estrogen receptor (ER) down-regulator (SERD) used in ER-positive metastatic breast cancer (MBC). Nearly all patients develop resistance. We performed molecular analysis of circulating tumor cells (CTC) to gain insight into fulvestrant resistance. Preclinical studies were performed with cultured breast cancer cells spiked into human blood and analyzed on the CellSearch(®) system. Clinical data are limited to a subset of patients with ER-positive MBC from a previously reported pilot trial whose disease was progressing on fulvestrant (N = 7) or aromatase inhibitors (AIs) (N = 10). CTCs were enumerated and phenotyped for ER and B-cell lymphoma (BCL2) using the CellSearch(®) CXC kit. In preclinical modeling, tamoxifen and AIs resulted in stabilized ER expression, whereas fulvestrant eliminated it. Five of seven patients progressing on fulvestrant had ≥5CTC/7.5 ml WB. Two of these five, treated with 500 mg/month fulvestrant, had no detectable CTC-expression of ER and BCL2 (an ER regulated gene). Three patients had heterogeneous CTC-ER and BCL2 expression indicating incomplete degradation of the ER target by fulvestrant. Two of these patients received 250 mg/month whereas the third patient received 500 mg/month fulvestrant. Her cancer harbored a mutation (Y537S) in the estrogen receptor alpha gene (ESR1). All seven ER positive patients progressing on AIs had heterogeneous CTC-ER expression. These results suggest heterogeneous mechanisms of resistance to fulvestrant, including insufficient dosage, ESR1 mutation, or conversion to dependence on non-ER pathways. CTC enumeration, phenotyping, and genotyping might identify patients who would benefit from fulvestrant dose escalation versus switching to alternative therapies.

Paoletti|Costanza|C|
Larios|Jose M|JM|
Muñiz|Maria C|MC|
Aung|Kimberly|K|
Cannell|Emily M|EM|
Darga|Elizabeth P|EP|
Kidwell|Kelley M|KM|
Thomas|Dafydd G|DG|
Tokudome|Nahomi|N|
Brown|Martha E|ME|
Connelly|Mark C|MC|
Chianese|David A|DA|
Schott|Anne F|AF|
Henry|N Lynn|NL|
Rae|James M|JM|
Hayes|Daniel F|DF|

D047072:Aromatase Inhibitors
D014408:Biomarkers, Tumor
D045744:Cell Line, Tumor
D019008:Drug Resistance, Neoplasm
D004958:Estradiol
D000077267:Fulvestrant
D006801:Humans
D009360:Neoplastic Cells, Circulating
D011960:Receptors, Estrogen
D016896:Treatment Outcome

Fulvestrant
Breast cancer
Circulating tumor cells (CTC)
Aromatase inhibitors
Hormone receptor positive


Risk factors for vasoplegia after cardiac surgery: a meta-analysis.

Abstract:
OBJECTIVES
Postoperative vasoplegia (PV) is a common haemodynamic disorder after cardiac surgery and is associated with high operative mortality. Preventive and potent therapeutic measures are critical to improve the outcome. Identification of risk factors for PV may increase awareness and prompt therapeutic action. Our objective was to pool the available evidence on the risk factors for PV in cardiac surgery and to perform a meta-analysis.

METHODS
PubMed, Embase, Ovid and Google Scholar databases were searched for studies published between 1965 and 2017. Three investigators independently screened the studies and extracted the data. Pooled estimates were obtained by a random effects model. Preoperative and operative patient data were gathered to determine their association with PV.

RESULTS
The search yielded 109 potential studies for inclusion. Of these, 10 articles were analysed and their data extracted. The total number of patients included was 30 035 patients (1524 with vasoplegia and 28 511 without vasoplegia). The only preoperative variable that was significantly associated with PV was renal failure [odds ratio (OR) 1.47; 95% confidence interval (CI) 1.17-1.86]. Patients with isolated coronary artery bypass grafting had a lower risk for PV (OR 0.36; 95% CI 0.22-0.59), whereas previous cardiac surgery (OR 2.03; 95% CI 1.27-3.26) and combined procedures increased its incidence (OR 2.12; 95% CI 1.82-2.47). PV increased with higher use of red blood cells (OR 2.12; 95% CI 1.82-2.47), longer aortic cross-clamp (mean difference 8.15 min; 95% CI 8.79-27.50 min) and cardiopulmonary bypass (mean difference 25.72 min; 95% CI 12.75-38.69 min) duration.

CONCLUSIONS
Patients with renal failure, higher use of red blood cell, longer and combined cardiac surgery procedures are at a higher risk for PV. Measures to promptly identify and treat PV in these patients should be considered.


Epidemiology of left ventricular hypertrophy in hypertension: implications for the clinic.

Abstract:
INTRODUCTION
Left ventricular hypertrophy (LVH) is a common complication to hypertension, indicating the presence of hypertensive heart disease, which puts the patient at a very high risk for subsequent clinical cardiovascular events like sudden cardiac death, stroke, myocardial infarction and heart failure.

AREAS COVERED
The epidemiology of LVH has changed in recent years as a consequence of the development of new diagnostic tools and demographic changes in hypertensive populations. Expert commentary: In individual hypertensive patients, the presence and type of LVH and associated systolic and diastolic myocardial dysfunction is modified by the co-presence of other cardiovascular risk factors and comorbidities and as well as activation of the reninangiotensin-aldosterone system and other molecular mechanisms involved in LVH pathophysiology. The purpose of this review is to give a clinical update on LVH in hypertension.

Left ventricular hypertrophy
hypertensive heart disease
arterial hypertension
echocardiography
left ventricular concentric geometry
left ventricular diastolic function
left ventricular systolic function
myocardial function
obesity
sex


Identification of two novel foot-and-mouth disease virus cytotoxic T lymphocyte epitopes that can bind six SLA-I proteins.

Abstract: Currently available vaccines from inactivated foot-and-mouth disease virus (FMDV) only protect animals by inducing neutralizing antibodies. A vaccine that contains cytotoxic T lymphocytes (CTL) epitopes to induce strong CTL responses might protect animals more effectively. Herein, we used swine leukocyte antigen class I (SLAI) proteins derived from six different strains of domestic pigs to screen and identify shared FMDV CTL epitopes. Four potential FMDV CTL epitopes (Q01, Q02, AS3, and QA4) were confirmed by mass spectrometry. We also determined the antigenicity of these epitopes to elicit cell-mediated immunoresponse by the ELISPOT and CTL assays. Among the four peptides, Q01 and QA4 were found to bind all six SLA-I proteins with strong affinity and elicit significant activity of CTL (P < 0.01). We conclude that Q01 and QA4 peptides are novel shared epitopes that can be recognized by all six SLA-I molecules on representative CTLs.

Gao|Feng-Shan|FS| Zhai|Xiao-Xin|XX| Jiang|Ping|P| Zhang|Qiang|Q| Gao|Hua|H| Li|Zi-Bin|ZB| Han|Yong|Y| Yang|Jie|J| Zhang|Zong-Hui|ZH|

D000818:Animals
D057134:Antibodies, Neutralizing
D018984:Epitopes, T-Lymphocyte
D004926:Escherichia coli
D005536:Foot-and-Mouth Disease
D029544:Foot-and-Mouth Disease Virus
D008297:Male
D011485:Protein Binding
D013045:Species Specificity
D013552:Swine
D013602:T-Lymphocytes, Cytotoxic

Foot-and-mouth disease virus
Cytotoxic T lymphocyte
Epitope
Swine leukocyte antigen
Peptide
Major histocompatibility complex


A deviation too many? Healthcare professionals' knowledge and attitudes concerning patients with intellectual disability disrupting norms regarding sexual orientation and/or gender identity.

Abstract:
BACKGROUND
People with intellectual disability (ID) have few role models for sexual expression and behaviour, and those who identify as LGBTQ experience dual marginalization. The aim of this study is to explore knowledge and attitudes concerning patients with both ID and norm-breaking sexuality and/or gender identity among healthcare professionals in habilitation centres.

METHOD
Data were collected from four focus group interviews that included 19 healthcare professionals from child and adult teams at two Swedish habilitation centres. Data were analysed using thematic analysis.

RESULTS
Three themes were identified as follows: heteronormative treatment in health care, barriers for inclusion and possibilities for inclusion.

CONCLUSIONS
Norm-breaking sexuality and gender identity are still relatively invisible in habilitation centres. People with ID are still predominately desexualized and perceptions regarding their sexuality are lagging behind the rest of society. Conditions that allow for more LGBTQ-affirmative practice were described by the teams that have undergone LGBTQ training.

D007722:Health Knowledge, Attitudes, Practice

healthcare professional
intellectual disability
LGBTQ
habilitation
thematic analysis
heteronormativity


Comprehensive nursing intervention combined with early activityactivity applied in ventilator-associated pneumonia and its influence on blood gas index.

Abstract:
OBJECTIVE
To study the application effect of comprehensive nursing combined with early activityactivity in patients with ventilator-associated pneumonia (VAP) and its influence on blood gas indexes of patients.

METHODS
100 patients with VAP admitted to our hospital from February 2018 to November 2019 were randomly selected and divided into control group and experimental group, with 50 patients in each group. Patients in the control group received routine nursing intervention with early activity, and patients in the experimental group received comprehensive nursing intervention with early activity. The incidence of adverse reactions, length of hospital stay, blood gas index, nursing efficiency, and nursing satisfaction were compared between the two groups.

RESULTS
Compared with the control group, the incidence of adverse reactions, mental status scale in non-psychiatric settings (MSSNS) score and length of hospital stay in the experimental group were noticeably lower (P<0.05), while the partial arterial oxygen pressure (PaO2) and saturation of blood oxygen (SaO2) in the experimental group were higher (P<0.05), and the arterial partial pressure carbon dioxide (PaCO2) in the experimental group was significantly lower (P<0.05). Nursing efficiency in the experimental group was significantly higher than the control group (P<0.05). Experimental group exhibited higher satisfaction rate compared to the control group (P<0.05).

CONCLUSION
Comprehensive nursing intervention combined with early activityactivity can significantly reduce the incidence of adverse reactions and hospital stay, improve the blood gas indicators of patients, and promote nursing efficiency.

Li|Zhen|Z| Xu|Liying|L| Wang|Yunxia|Y| Gao|Haipeng|H|

Comprehensive nursing
early activityactivity
ventilator-associated pneumonia
blood gas index
nursing effect


Biocatalysis at Work: Applications in the Development of Sagopilone.

Abstract: For the antitumour agent sagopilone, an epothilone analogue, a large-scale synthesis was developed to synthesise the active pharmaceutical ingredient for clinical trials, exploring enzymatic and microbial methods to produce chiral building blocks on a multi-kilogram scale. The three building blocks were identified as key intermediates in the synthesis and needed to be produced with high optical purity in yields higher than those previously published. The improved syntheses of two of these building blocks are detailed herein. For building block A, the chemical research synthesis was abandoned, and a novel chemical route was developed leading to building block A via an enzymatic hydrolysis process. For building blocks C, replacement of a chemical catalytic procedure by a microbial process meant that the development of a new starting material could be avoided, thereby accelerating the development process. For the clinical development process, a human metabolite of sagopilone was required as a reference. To accelerate the synthesis of the metabolite, no chemical synthesis was investigated; rather, we relied solely on oxidoreductases. The human metabolite of sagopilone was synthesised on a multi-gram scale in a single-step process using genetically engineered E. coli expressing human cytochrome P450 enzyme 2C19. The integration of enzymatic and microbial processes provided tools that enable the synthesis of highly functionalised intermediates and metabolites.

Gottfried|Kathrin|K| Klar|Ulrich|U| Platzek|Johannes|J| Zorn|Ludwig|L|

biocatalysis
oxidoreductases
enzymes
antitumor agents
gene expression


A study of clinical implementation of ventricular septal defect closure using three transthoracic approaches.

Abstract:
OBJECTIVE
To investigate the clinical implementation of ventricular septal defect closure using the three transthoracic approaches.

METHODS
A total of 70 children with septal defects admitted to our hospital from January 2017 to December 2020 were selected as the study subjects. Among them, 10 children with the left thorax-right ventricle-left ventricle approach were assigned to Group A, 8 children with the right thorax-atrium dextrum-right ventricle-left ventricle approach were assigned to Group B, and 52 children with the subxyphoid-right ventricle-left ventricle approach were assigned to Group C. The surgical indices were recorded, the success rates of closure and cardiopulmonary function indices were compared, electrocardiogram (ECG), echocardiogram and X-ray film were investigated at 1, 3 and 12 months after surgery, and the incidence of complications was recorded.

RESULTS
There was no statistically significant difference in the success rate of closure among the three groups (P > 0.05). The duration of intracardiac operations in Groups A and C was remarkably shorter than that in Group B, and the duration of skin incision and suture and hospital stay in Groups A and B were noticeably shorter than those in Group C (P < 0.05). After surgery, there was statistically significant difference in the contents of creatine kinase MB (CK-MB) isoenzyme, lactate dehydrogenase (LDH), serum malondialdehyde (MDA) and superoxide dismutase (SOD) among the three groups (P > 0.05). Airway resistance (Raw), oxygenation index (OI), and alveolar-arterial oxygen gradient (AaDO2) indicated that the postoperative pulmonary function in Group C was more effectively protected. There was no statistically significant difference in the incidence of complications among the three groups (P > 0.05).

CONCLUSION
Ventricular septal defect closure using the three transthoracic approaches exhibited a high success rate and a high safety profile.

Cai|Longren|L| Zeng|Ganhua|G| Li|Yan|Y| Peng|Xinghua|X|

ventricular septal defect
closure
transthoracic approaches
Children
echocardiogram
minimal invasiveness


Film Thickness Determines Cell Growth and Cell Sheet Detachment from Spin-Coated Poly(N-Isopropylacrylamide) Substrates.

Abstract: Poly(N-isopropylacrylamide) (pNIPAm) is widely used to fabricate thermoresponsive surfaces for cell sheet detachment. Many complex and expensive techniques have been employed to produce pNIPAm substrates for cell culture. The spin-coating technique allows rapid fabrication of pNIPAm substrates with high reproducibility and uniformity. In this study, the dynamics of cell attachment, proliferation, and function on non-cross-linked spin-coated pNIPAm films of different thicknesses were investigated. The measurements of advancing contact angle revealed increasing contact angles with increasing film thickness. Results suggest that more hydrophilic 50 and 80 nm thin pNIPAm films are more preferable for cell sheet fabrication, whereas more hydrophobic 300 and 900 nm thick spin-coated pNIPAm films impede cell attachment. These changes in cell behavior were correlated with changes in thickness and hydration of pNIPAm films. The control of pNIPAm film thickness using the spin-coating technique offers an effective tool for cell sheet-based tissue engineering.

Dzhoyashvili|Nina A|NA|
Thompson|Kerry|K|
Gorelov|Alexander V|AV|
Rochev|Yuri A|YA|

film thickness
spin-coating
pNIPAm
cell sheet engineering
protein adsorption
wettability


Radiomics nomogram based on MRI for predicting white matter hyperintensity progression in elderly adults.

Abstract:
BACKGROUND
White matter hyperintensity (WMH) is widely observed in aging brain and is associated with various diseases. A pragmatic and handy method in the clinic to assess and follow up white matter disease is strongly in need.

PURPOSE
To develop and validate a radiomics nomogram for the prediction of WMH progression.

STUDY TYPE
Retrospective.

POPULATION
Brain images of 193 WMH patients from the Picture Archiving and Communication Systems (PACS) database in the A Medical Center (Zhejiang Provincial People's Hospital). MRI data of 127 WMH patients from the PACS database in the B Medical Center (Zhejiang Lishui People's Hospital) were included for external validation. All of the patients were at least 60 years old.

FIELD STRENGTH/SEQUENCE
T1 -fluid attenuated inversion recovery images were acquired using a 3T scanner.

ASSESSMENT
WMH was evaluated utilizing the Fazekas scale based on MRI. WMH progression was assessed with a follow-up MRI using a visual rating scale. Three neuroradiologists, who were blinded to the clinical data, assessed the images independently. Moreover, interobserver and intraobserver reproducibility were performed for the regions of interest for segmentation and feature extraction.

STATISTICAL TESTS
A receiver operating characteristic (ROC) curve, the area under the curve (AUC) of the ROC was calculated, along with sensitivity and specificity. Also, a Hosmer-Lemeshow test was performed.

RESULTS
The AUC of radiomics signature in the primary, internal validation cohort, external validation cohort were 0.886, 0.816, and 0.787, respectively; the specificity were 71.79%, 72.22%, and 81%, respectively; the sensitivity were 92.68%, 87.94% and 78.3%, respectively. The radiomics nomogram in the primary cohort (AUC = 0.899) and the internal validation cohort (AUC = 0.84). The Hosmer-Lemeshow test showed no significant difference between the primary cohort and the internal validation cohort (P > 0.05). The AUC of the radiomics nomogram, radiomics signature, and hyperlipidemia in all patients from the primary and internal validation cohort was 0.878, 0.848, and 0.626, respectively.

DATA CONCLUSION
This multicenter study demonstrated the use of a radiomics nomogram in predicting the progression of WMH with elderly adults (an age of at least 60 years) based on conventional MRI.

LEVEL OF EVIDENCE
3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:535-546.

Shu|Zhen-Yu|ZY| Shao|Yuan|Y| Xu|Yu-Yun|YY| Ye|Qin|Q| Cui|Si-Jia|SJ| Mao|De-Wang|DW| Pang|Pei-Pei|PP| Gong|Xiang-Yang|XY|0000-0002-2785-3308

radiomics
nomogram
white matter hyperintensity
progression
magnetic resonance imaging


Targeted disruption of dual leucine zipper kinase and leucine zipper kinase promotes neuronal survival in a model of diffuse traumatic brain injury.

Abstract:
BACKGROUND
Traumatic brain injury (TBI) is a major cause of CNS neurodegeneration and has no disease-altering therapies. It is commonly associated with a specific type of biomechanical disruption of the axon called traumatic axonal injury (TAI), which often leads to axonal and sometimes perikaryal degeneration of CNS neurons. We have previously used genome-scale, arrayed RNA interference-based screens in primary mouse retinal ganglion cells (RGCs) to identify a pair of related kinases, dual leucine zipper kinase (DLK) and leucine zipper kinase (LZK) that are key mediators of cell death in response to simple axotomy. Moreover, we showed that DLK and LZK are the major upstream triggers for JUN N-terminal kinase (JNK) signaling following total axonal transection. However, the degree to which DLK/LZK are involved in TAI/TBI is unknown.

METHODS
Here we used the impact acceleration (IA) model of diffuse TBI, which produces TAI in the visual system, and complementary genetic and pharmacologic approaches to disrupt DLK and LZK, and explored whether DLK and LZK play a role in RGC perikaryal and axonal degeneration in response to TAI.

RESULTS
Our findings show that the IA model activates DLK/JNK/JUN signaling but, in contrast to axotomy, many RGCs are able to recover from the injury and terminate the activation of the pathway. Moreover, while DLK disruption is sufficient to suppress JUN phosphorylation, combined DLK and LZK inhibition is required to prevent RGC cell death. Finally, we show that the FDA-approved protein kinase inhibitor, sunitinib, which has activity against DLK and LZK, is able to produce similar increases in RGC survival.

CONCLUSION
The mitogen-activated kinase kinase kinases (MAP3Ks), DLK and LZK, participate in cell death signaling of CNS neurons in response to TBI. Moreover, sustained pharmacologic inhibition of DLK is neuroprotective, an effect creating an opportunity to potentially translate these findings to patients with TBI.

Welsbie|Derek S|DS|0000-0002-3772-9335
Ziogas|Nikolaos K|NK|
Xu|Leyan|L|
Kim|Byung-Jin|BJ|
Ge|Yusong|Y|
Patel|Amit K|AK|
Ryu|Jiwon|J|
Lehar|Mohamed|M|
Alexandris|Athanasios S|AS|
Stewart|Nicholas|N|
Zack|Donald J|DJ|
Koliatsos|Vassilis E|VE|

D000818:Animals
D000070642:Brain Injuries, Traumatic
D002470:Cell Survival
D004195:Disease Models, Animal
D016350:Leucine Zippers
D020930:MAP Kinase Kinase Kinases
D020935:MAP Kinase Signaling System
D008297:Male
D008810:Mice, Inbred C57BL
D009474:Neurons
D047428:Protein Kinase Inhibitors
D012165:Retinal Ganglion Cells

Dual leucine zipper kinase
Traumatic brain injury
Traumatic axonal injury
Retinal ganglion cell
DLK
LZK
Cell death
Concussion
Optic neuropathy


Bone marrow mesenchymal stem cells combined with minocycline improve spinal cord injury in a rat model.

Abstract: The aims of this study were to assess that the effects of bone marrow mesenchymal stem cells (BMSCs) combination with minocycline improve spinal cord injury (SCI) in rat model. In the present study, the Wistar rats were randomly divided into five groups: control group, SCI group, BMSCs group, Minocycline group and BMSCs + minocycline group. Basso, Beattie and Bresnahan (BBB) test and MPO activity were used to assess the effect of combination therapy on locomotion and neutrophil infiltration. Inflammation factors, VEGF and BDNF expression, caspase-3 activation, phosphorylation-p38MAPK, proNGF, p75NTR and RhoA expressions were estimated using commercial kits or western blot, respectively. BBB scores were significantly increased and MPO activity was significantly undermined by combination therapy. In addition, combination therapy significantly decreased inflammation factors in SCI rats. Results from western blot showed that combination therapy significantly up-regulated the protein of VEGF and BDNF expression and down-regulated the protein of phosphorylation-p38MAPK, proNGF, p75NTR and RhoA expressions in SCI rats. Combination therapy stimulation also suppressed the caspase-3 activation in SCI rats. These results demonstrated that the effects of bone marrow mesenchymal stem cells combination with minocycline improve SCI in rat model.

Chen|Dayong|D| Zeng|Wei|W| Fu|Yunfeng|Y| Gao|Meng|M| Lv|Guohua|G|

D045164:Mesenchymal Stem Cell Transplantation

Bone marrow mesenchymal stem cells
minocycline
spinal cord injury
inflammation
VEGF and BDNF


A new extinct species of alligator lizard (Squamata: Elgaria) and an expanded perspective on the osteology and phylogeny of Gerrhonotinae.

Abstract:
BACKGROUND
Alligator lizards (Gerrhonotinae) are a well-known group of extant North American lizard. Although many fossils were previously referred to Gerrhonotinae, most of those fossils are isolated and fragmentary cranial elements that could not be placed in a precise phylogenetic context, and only a handful of known fossils are articulated skulls. The fossil record has provided limited information on the biogeography and phylogeny of Gerrhonotinae.

RESULTS
We redescribe a nearly complete articulated fossil skull from the Pliocene sediments of the Anza-Borrego Desert in southern California, and refer the specimen to the alligator lizard genus Elgaria. The fossil is a representative of a newly described species, Elgaria peludoverde. We created a morphological matrix to assess the phylogeny of alligator lizards and facilitate identifications of fossil gerrhonotines. The matrix contains a considerably expanded taxonomic sample relative to previous morphological studies of gerrhonotines, and we sampled two specimens for many species to partially account for intraspecific variation. Specimen-based phylogenetic analyses of our dataset using Bayesian inference and parsimony inferred that Elgaria peludoverde is part of crown Elgaria. The new species is potentially related to the extant species Elgaria kingii and Elgaria paucicarinata, but that relationship was not strongly supported, probably because of extensive variation among Elgaria. We explored several alternative biogeographic scenarios implied by the geographic and temporal occurrence of the new species and its potential phylogenetic placements.

CONCLUSIONS
Elgaria peludoverde is the first described extinct species of Elgaria and provides new information on the biogeographic history and diversification of Elgaria. Our research expands the understanding of phylogenetic relationships and biogeography of alligator lizards and strengthens the foundation of future investigations. The osteological data and phylogenetic matrix that we provided will be critical for future efforts to place fossil gerrhonotines. Despite limited intraspecific sampled sizes, we encountered substantial variation among gerrhonotines, demonstrating the value of exploring patterns of variation for morphological phylogenetics and for the phylogenetic placement of fossils. Future osteological investigations on the species we examined and on species we did not examine will continue to augment our knowledge of patterns of variation in alligator lizards and aid in phylogenetics and fossil placement.

Scarpetta|Simon G|SG|
Ledesma|David T|DT|
Bell|Christopher J|CJ|

Elgaria Osteology Gerrhonotinae Fossils Phylogenetics Biogeography Pliocene Anza-Borrego Morphology


Total synthesis of ramonanins A-D.

Abstract: The first total synthesis of the ramonanin family of lignan natural products is described. The short synthesis involves a 2,5-diaryl-3,4-dimethylene tetrahydrofuran intermediate, which participates in an unexpectedly facile Diels-Alder dimerization, generating all four natural products. Insights into the reactivity and stereoselectivity of the key dimerization are provided through computational studies employing B3LYP/6-31G(d) and M06-2X/6-31G(d) model chemistries.

Harvey|Ross S|RS|
Mackay|Emily G|EG|
Roger|Lukas|L|
Paddon-Row|Michael N|MN|
Sherburn|Michael S|MS|
Lawrence|Andrew L|AL|

lignans
natural products
Diels-Alder reactions
biomimetic synthesis
enyne metathesis


Beyond the 90-90-90: refocusing HIV prevention as part of the global HIV response.

Abstract:
INTRODUCTION
The remarkable expansion in availability of antiretroviral therapy (ART) over the past two decades has transformed HIV infection into a manageable chronic condition. People with HIV infection now live long and healthy lives on treatment that is simpler, safer and cheaper. According to UNAIDS estimates, the global coverage of ART reached 46% in 2015, resulting in a 26% decrease in annual HIV-related deaths since 2010. Such success has positioned treatment access at the centre of the global HIV response as a way to prevent mortality, morbidity and HIV transmission through a "Treat All" approach. Continuing expansion of treatment is needed to further reduce HIV-related mortality. This progress with treatment, however, masks a stagnation in the estimated annual number of new HIV infections. Continuing levels of HIV incidence despite treatment scale-up stem from several factors, which should be addressed in order to prevent new infections and decrease the numbers of people requiring treatment in the future.

DISCUSSION
ART can only reach those already diagnosed, and although it is unclear what proportion of new infections occur during acute and early infection prior to treatment initiation, phylogenetic studies suggest that it might be substantial. Thus, better testing approaches to reach the 40% of people with undiagnosed HIV infection as early as possible are critical. New approaches to reach men, young people and key populations, where HIV risk is highest and HIV prevention, testing and treatment coverage is lowest, are also needed. Overall coverage of effective prevention interventions remains low, enabling HIV transmission to occur, or time is required to show population-level effects. For example, the full impact of the medical male circumcision intervention will be seen once a larger proportion of men in age cohorts with high incidence are circumcised. Finally, strategically focused pre-exposure prophylaxis interventions have the potential to prevent HIV acquisition among populations at substantial risk, averting treatment costs in coming years.

CONCLUSIONS
The United Nations (UN) targets to end AIDS include the "90-90-90" targets for HIV diagnosis, treatment and viral suppression. While 90-90-90 has been widely emphasized and adopted by countries and international funders, the focus thus far has largely been on increasing access to ART - the second "90." A similar emphasis on achieving UN HIV prevention targets and adequate funding for meeting these is essential, alongside treatment, in order to reduce population-level incidence and change the trajectory of the HIV epidemic over the long term.

Baggaley|Rachel|R| Dalal|Shona|S| Johnson|Cheryl|C| Macdonald|Virginia|V| Mameletzis|Ioannis|I| Rodolph|Michelle|M| Figueroa|Carmen|C| Samuelson|Julia|J| Verster|Annette|A| Doherty|Meg|M| Hirnschall|Gottfried|G|

HIV prevention
antiretroviral therapy
key populations
PrEP
voluntary medical male circumcision