bluuebunny/crossref_metadata_2025 huggingface dataset:
Rural Graduate Medical Education: Choosing the Road “Less Traveled By”
Authors: Pauwels Judith
Published: May 2022

Despite active efforts to improve access to health care for people who live in rural communities, the need for developing a physician workforce that is committed to rural practice, and with the professional and personal skills that will best fit with the needs of the rural community, is only increasing over time. Supporting and solidifying the rural graduate medical education landscape must be a crucial piece of any plan to address gaps in rural health care. Embracing creative solutions that address the most important barriers to this development has high potential for meeting the health care needs of rural communities, with emphasis on the rural community stakeholders assuming the central role in planning efforts. In particular, essential innovations include developing a culture of learning in rural settings using concepts of a teaching health neighborhood and advancing interprofessional models of care; incorporating concepts of “place-based training” with focus on relational connectedness; enhancing a spectrum of potential partnerships, including rural and urban regional entities, the Health Resources and Services Administration, and other federal agencies (e.g., the Indian Health Service and Veterans Health Administration among others) to support the ability of rural health entities to embrace medical education; and advocating for federal and state funding initiatives to ensure the sustainability of training programs in rural communities. Although not sufficient to guarantee improved access to health care and better health outcomes among rural communities, robust collaborations to develop interprofessional training and enhancement of the entire pipeline of health professions training and practice holds significant promise for improving the health of rural populations.
Trends in U.S. MD–PhD Program Matriculant Diversity by Sex and Race/Ethnicity
Authors: Martinez-Strengel Angela , Samuels Elizabeth A. , Cross Jeremiah , Cramer Laura D. , Desai Mayur M. , Gotian Ruth , Gross Cary P. , Latimore Darin , Cavazos Jose E. , Boatright Dowin
Published: May 2022

Purpose

To examine demographic characteristics of matriculants to U.S. MD–PhD programs by sex and race/ethnicity from academic years (AYs) 2009–2018 and explore the relationships between trends in the percentage of female and underrepresented minority (URM) matriculants to programs with and without Medical Scientist Training Program (MSTP) funding.

Method

Linear regression and time trend analysis of the absolute percentage of matriculants into all U.S. MD–PhD programs was performed for self-reported sex and race/ethnicity, using Association of American Medical Colleges data for AYs 2009–2018, including an interaction for MSTP funding status (yes/no) and year. Linear regression of the percentage of programs matriculating no female or no URM students between AYs 2009 and 2018 was performed, focusing on programs in the top 3 quartiles by size (i.e., those matriculating 4 or more students per year).

Results

Between AYs 2009 and 2018, the percentage of matriculants to all MD–PhD programs who were female (38.0%–46.0%, 1.05%/year, P = .002) or URM (9.8%–16.7%, 0.77%/year, P < .001) increased. The annual percentage gains of URM matriculants were greater at MSTP-funded programs compared with non-MSTP-funded programs (0.50%/year, P = .046). Moreover, among MD–PhD programs in the top 3 quartiles by size, the percentage of programs with no female matriculants decreased by 0.40% per year (P = .02) from 4.6% in 2009 to 1.6% in 2018, and the percentage of programs with no URM matriculants decreased by 3.41% per year (P < .001) from 49% in 2009 to 22% in 2018.

Conclusions

A consistent and sustained increase in the percentage of female and URM matriculants to MD–PhD programs from AYs 2009–2018 was observed, but the annual increases in the percentages across groups were small, and the demographics of the MD–PhD workforce still do not reflect the diversity of the U.S. general population.
Remote and Hybrid Schooling During COVID-19: Associations with Child Behavior and Sleep
Authors: Levitt Kimberley J. , Munzer Tiffany , Torres Chioma , Schaller Alexandria , McCaffery Harlan , Radesky Jenny S.
Published: May 2022

Objective:

The purpose of this study was to assess the prevalence of child behavior, academic and sleep concerns, and parent stress and depression symptoms during COVID-19; to test associations of parent-child well-being with child school format; and to examine effect moderation by child race/ethnicity and material hardship.

Methods:

A total of 305 English-speaking parents of elementary school-age children completed online surveys regarding demographics, child school format, behavior, learning-related experiences, sleep, and parent stress and depression symptoms. Multivariable linear and logistic regression analyses examined associations of school format with child and parent outcomes.

Results:

Children were aged 5.00 to 10.99 years, with 27.8% underrepresented minority race/ethnicity. Per parental report, 27.7% attended school in-person, 12.8% hybrid, and 59.5% remote. In multivariable models, compared with children receiving in-person instruction, children receiving remote instruction exhibited more hyperactivity (β 0.94 [95% confidence interval, 0.18–1.70]), peer problems (β 0.71 [0.17–1.25]), and total behavioral difficulties (β 2.82 [1.11–4.53]); were less likely to show academic motivation (odds ratio [OR] 0.47 [0.26–0.85]) and social engagement (OR 0.13 [0.06–0.25]); were more likely to show schoolwork defiance (OR 2.91 [1.56–5.40]); and had a later sleep midpoint (β 0.37 [0.18–0.56]) and higher odds of cosleeping (OR 1.89 [1.06–3.37]). Associations of remote learning with behavior difficulties were stronger for children without material hardships.

Conclusion:

Children receiving remote and hybrid instruction were reported to have more difficulties compared with children receiving in-person instruction. Children with material hardships showed more behavior challenges overall but less associated with school format. Therefore, planning for a return to in-person learning should also include consideration of family supports.
Parenting Children with Cystic Fibrosis: Developmental Acquisition of Expertise
Authors: Tluczek Audrey , Grob Rachel , Warne Emily , Van Gorp Stacy , Greene Lisa , Homa Karen
Published: May 2022

Objective:

This study was designed to increase our understanding of parents' experiences managing the needs of their children with cystic fibrosis (CF) and to identify potential gaps in services.

Method:

We used grounded dimensional analysis of anonymous survey data obtained from a quality improvement initiative conducted by the Cystic Fibrosis Foundation (CFF). The Patient and Family Experience of Care (PFEC) survey was administered continuously at 125 CF care centers throughout the United States in 2017. The subsample of data for this study was completed by 80 parents/caregivers of children with CF (younger than 18 years).

Results:

Two unifying themes emerged from parents' survey responses: (1) parents' expertise expands continually as they learn and adapt to changes in their children's maturity or health and (2) parental expertise is sometimes visible or invisible to clinicians. Parents' expertise evolved with their children's development. Visible to care teams was at-home care, e.g., respiratory treatments and medications. Less visible were intangible management activities, e.g., social processes, emotions, and concerns that were omnipresent for parents but seldom disclosed to or seen/recognized by clinicians. Themes, such as the quality of encounters with care teams, progressive nature of CF, and hope derived from advances in research, were associated with specific contextual factors.

Conclusion:

The findings expand our understanding of lived parental experiences of CF across childhood and offer direction for future quality improvement and research. Online parent surveys offer a valuable tool to identify unmet needs across subgroups of families affected by chronic childhood health conditions.
Cheek Donor Site for Full-Thickness Skin Graft Repair of the Nasal Ala: Outcomes of a Retrospective Cohort Study
Authors: Du Eric Y. , Moody Rylee A. , Armbrecht Eric S. , Chen Collin L. , Maher Ian A. , Bernstein Michael L. , Behshad Ramona
Published: May 2022

BACKGROUND

Full-thickness skin grafts (FTSGs) are useful repairs for reconstructing nasal alar defects. Traditional donor sites include the preauricular, postauricular, and supraclavicular skin.

OBJECTIVE

To evaluate esthetic outcomes and complications of nasal alar defects repaired with FTSGs from the medial cheek.

MATERIALS AND METHODS

A retrospective chart review of Mohs surgery patients who had FTSG repair of the nasal ala between January 2015 and August 2020 was performed. Demographic, surgery, and follow-up visit data were reviewed. Cosmesis was rated by a facial plastic surgeon, a Mohs surgeon, and a plastic surgeon using baseline, defect, and follow-up visit photographs.

RESULTS

Sixty-nine patients with FTSG repairs of nasal alar defects were identified. 51 of 69 patients (73.9%) had the cheek donor site, and 18 of 69 patients (26.1%) had a noncheek donor site. The mean (SD) rater visual analog score for both cohorts was good with no significant difference (cheek: 65.9 [13.8]; noncheek: 66.1 [15.3]; p = .96). A notable difference in the complication rate by donor site was observed (cheek: 6.9%, noncheek: 16.7%; p = .13), although it did not reach significance.

CONCLUSION

The cheek is a reliable FTSG donor site for nasal alar defects after Mohs micrographic surgery, with a trend toward fewer complications.
Reliability and responsivity of pain intensity scales in individuals with chronic pain
Authors: Euasobhon Pramote , Atisook Raviwon , Bumrungchatudom Kulsiri , Zinboonyahgoon Nantthasorn , Saisavoey Nattha , Jensen Mark P.
Published: May 2022

Prior research supports the validity and short-term test–retest stability of 4 commonly used scales for assessing pain intensity (Visual Analogue Scale [VAS], 6-point Verbal Rating Scale [VRS-6], Numerical Rating Scale [NRS-11], and Face Pain Scale-Revised [FPS-R]). However, the relative stability and ability of these measures to detect changes in pain intensity over longer time periods have not yet been examined, although knowledge regarding these psychometric issues is important for selecting from among these measures. To address this knowledge gap, we administered these scales assessing worst and average pain intensity to 250 chronic pain outpatients on 2 occasions, a little over 6 weeks apart on average. All 4 scales were found to be valid for detecting decreases in pain, and the VAS, NRS-11, and FPS-R evidenced the most validity for detecting increases in pain. The NRS-11 and VAS evidenced better test–retest stability than the VRS-6 and FPS-R. Age affected the ability of the VRS-6 for detecting improvement in worst pain, as well as the ability of the VAS for detecting worsening in both worst and average pain. However, the psychometric properties of the scales were not influenced by education level. Overall, the NRS-11 emerged as showing the most sensitivity and stability. The FPS-R seems to be a good second choice to consider for samples of individuals who might have difficulty understanding or using the NRS-11.
Prevalence and Characterization of Undiagnosed Youths at Risk of Chlamydia trachomatis Infection: A Cross-sectional Study
Authors: Reyes-Lacalle Azahara , Carnicer-Pont Dolors , Masvidal Miriam Gómez , Montero-Pons Laura , Cabedo-Ferreiro Rosa , Falguera-Puig Gemma
Published: May 2022

Objective

The aim of this study was to determine the prevalence of Chlamydia trachomatis infection in undiagnosed young people aged between 15 and 24 years.

Materials and Methods

A convenience sample of 623 youths, with a mean (SD) age of 20.1 (2.2) years, was recruited from key spaces in the North Metropolitan area of Barcelona in Catalonia, Spain. Participants completed a 21-item questionnaire and provided a urine sample or vaginal swab for testing.

Results

The most common age at the first sexual intercourse was 16 years (24.6%), followed by 15 years (21.3%). Only 32.6% reported always use of condoms, 49.2% sometimes, and 15.6% never. A positive test for chlamydia was found in 34 participants (5.5%; 95% CI, 3.8–7.5), with no difference by sex. A positive test was significantly more common among the participants who were working, who had been diagnosed with a sexually transmitted disease (STD) at some point in their life, and who used web pages/apps to find new sexual partners more than once a month. In the multivariate analysis, working status was an independent factor associated with chlamydial infection (adjusted odds ratio[OR], 8.88; 95% CI, 1.71–46.17), whereas not having been previously diagnosed with an STD (OR, 0.34; 95% CI, 0.07–1.49) and never using the Internet to find sexual partners (OR, 0.16; 95% CI, 0.03–080) were protective factors against chlamydial infection.

Conclusions

The prevalence of C. trachomatis infection was 5.5%. Working status, a previous diagnosis of STD, and use of the Internet to find new sexual partners were associated with chlamydial test positivity.
Comparison of efficacy and safety of traditional Chinese patent medicines for diabetic nephropathy
Authors: Liu Shilin , Li Andong , Jiang Bin , Mi Jia , Nan Hongmei , Bao Pengjie , Nan Zheng
Published: May 2022

Background:

Diabetic nephropathy (DN) is one of the most serious complications of diabetes. It has become a global public health problem among humans. DN is the leading cause of end-stage renal disease. At present, there is no specific medicine or modern medicinal therapy. In recent years, studies have shown that traditional Chinese patent medicines have been effective in treating DN, with few side effects. There is no systematic review on the treatment of DN with Chinese patent medicines. The current systematic review aims to evaluate the efficacy and safety of Chinese patent medicines for the treatment of DN.

Methods:

We will develop a search strategy to search major Chinese and English databases from inception to February 25, 2022 for randomized controlled trials examining the use of traditional Chinese patent medicine for the treatment of DN. The search will be conducted in accordance with the participants, interventions, comparisons, outcomes (PICOS) framework. Two researchers will use EndnoteX9 software to extract data and independently evaluate the quality of the included trials. Finally, the Bayesian network meta-analysis will be carried out by using software such as ReviewManager, Stata16.0, and WinBUGS1.4.3.

Results:

The primary outcomes will be urine albumin excretion rate, urea nitrogen, serum creatinine, total effective rate, and adverse events, and the secondary outcomes will be body mass index, fasting blood glucose, and 2-hPG during 75-g OGTT. These outcomes will be examined to provide a reliable basis for the treatment of DN with different traditional Chinese patent medicines.

Conclusion:

This review will compare the efficacy and safety of different traditional Chinese patent medicines for treating DN. The results of the study will provide a basis for the selection of adjuvant treatment options for DN.
Case report of Modified Viabahn Open Revascularization TEChnique (VORTEC) as a rescue strategy for hepatic artery dissection after initial endovascular treatment of postpancreaticoduodenectomy hemorrhage
Authors: Sng Yi Ping , Li Zhihao , Yen Hsu-Ting , Yong Chee Chien
Published: May 2022

Rationale:

Currently endovascular treatments are commonly utilized to treat postpancreaticoduodenectomy hemorrhage. However, when endovascular procedure went wrong, open surgery with ligation of the culprit vessels would be the most common salvage method. With Modified Viabahn Open Revascularization TEChnique (VORTEC), we can try to rescue the vessel without sacrificing it by introduction of another endovascular stent under direct method.

Patient concerns:

A 76-year-old man with stage IIIA ampulla vater adenocarcinoma underwent pancreaticoduodenectomy and experience pancreatic leak complicated with postpancreaticoduodenectomy hemorrhage.

Diagnosis:

Emergent angiography revealed extravasation from proper hepatic artery.

Interventions:

A 6 mm Viabahn stent was deployed but no distal runoff. Operation was shifted to emergent laparotomy and revealed intimal dissection of hepatic artery. Modified VORTEC was performed with guidewire redirected to true lumen and another stent was deployed under direct vision.

Outcomes:

Patient's hepatic artery was preserved and with no consequent liver failure.

Lesson:

Modified VORTEC method could be used as salvage strategy for artery dissection after initial endovascular treatment failed.
CT findings of basaloid squamous cell carcinoma of the lung in 12 patients
Authors: Kim Chu Hyun , Cha Yoon Ki , Han Joungho , Kim Jun Ho , Kim Tae Jung , Chung Myung Jin , Lee Jung Hee , Yoon Hyun Jung
Published: May 2022

Basaloid squamous cell carcinoma (SCC) is very rare subtype of SCC of the lung and it is important to distinguish basaloid to other subtypes of SCCs, since the prognosis of basaloid subtype is considered poorer than that of other non-basaloid subtypes of SCCs. Aim of this study was to assess computed tomography (CT) findings of basaloid SCC of the lung in 12 patients.

From January 2016 to April 2021, 12 patients with surgically proven basaloid SCC of the lung were identified. CT findings were analyzed, and the imaging features were compared with histopathologic reports. Clinical and demographic features were also analyzed.

Axial location of the tumor was central in 5 patients, while 7 was in peripheral. Of the 7 patients whose tumors were located in the peripheral, margin of the tumor were smooth (n 
= 2), lobulated (n 
= 2), or spiculated (n 
= 3). After contrast injection, net enhancement value ranged from 15.8 to 71.8 HU (median, 36.4 HU). Endobronchial growth were seen in 5 patients and these patients accompanied obstructive pneumonia or atelectasis. Internal profuse necrosis, cavitation, or calcifications were not seen.

On CT, basaloid squamous cell presents as solitary nodule or mass with moderate enhancement. Tumor was located either peripheral or central compartment of the lung and cavitation was absent.
Preliminary evaluation of a small interfering RNA molecular probe targeting murine double minute 2 in breast cancer
Authors: Wang Xinyu , Xu Peng , Jiao Yuying , Luan Sha , Gao Yue , Zhao Changjiu , Fu Peng
Published: May 2022

Introduction

Murine double minute 2 (MDM2) is an oncogene that is important in tumorigenesis, tumor metastasis and chemotherapy resistance. We aimed to synthesize a molecular imaging probe, 99mTc-HYNIC-siRNA 1489, which could specifically bind to MDM2. The [99mTc]HYNIC-siRNA 1489 molecular probe provided an effective way of assessing MDM2 expression via single-photon emission computed tomography.

Method

Three siRNAs were designed, and their inhibitory efficiencies were determined using western blots and qRT-PCR. The selected siRNA was labeled with the radionuclide technetium-99m (99mTc) through the chelator HYNIC. The bioactivity and properties of [99mTc]HYNIC-siRNA 1489 were evaluated prior to imaging in mice. Imaging and biodistribution of the probe were used to assess its targeting ability.

Results

SiRNA 1489, which was labeled with 99mTc, displayed a strong inhibitory effect in Michigan Cancer Foundation-7 cell lines. The radiochemical purity of [99mTc]HYNIC-siRNA 1489 was stable at various temperatures in phosphate-buffered serum and bovine serum. The tumor/muscle ratio in mice injected with [99mTc]HYNIC-siRNA 1489 was higher than that in those injected with the negative control, [99mTc]HYNIC-NC siRNA. The percentage injected dose per gram (%ID/g) of the tumors injected with 99mTc-HYNIC-siRNA 1489 was greater than that of the control group.

Conclusion

The [99mTc]HYNIC-siRNA 1489 was taken up by the tumor, which had a high level of MDM2. The probe exhibited a sufficient retention time in the tumor. This probe may be an effective strategy for evaluating MDM2 expression and achieving early diagnosis in breast cancer.
Dissertation Topics in Nursing
Authors: Dieckmann Nathan F. , Stoyles Sydnee A. , Aebischer Jonathan H. , Olvera-Alvarez Hector A.
Published: May 2022

Background

Few quantitative studies have documented the types of research topics most commonly employed by nursing PhD students and whether they differ by program delivery (in-person vs. online/hybrid programs).

Objectives

We examined a large set of publicly available PhD dissertation abstracts to (a) describe the relative prevalence of different research topics and methods and (b) test whether the primary topics and methods used differed between online or hybrid and in-person PhD programs. A secondary goal was to introduce the reader to modern text-mining approaches to generate insights from a document corpus.

Methods

Our database consisted of 2,027 dissertation abstracts published between 2015 and 2019. We used a structural topic modeling text-mining approach to explore PhD students’ research topics and methods in United States-based doctoral nursing programs.

Results

We identified 24 different research topics representing a wide range of research activities. Most of the research topics identified did not differ in prevalence between online/hybrid and in-person programs. However, online/hybrid programs were more likely to engage students in research focused on nursing education, professional development, work environment, simulation, and qualitative analysis. Pediatrics, sleep science, older adults and aging, and chronic disease management were more prevalent topics in in-person-only programs.

Discussion

The range of topics identified highlights the breadth of research nursing PhD students’ conduct. Both in-person and online/hybrid programs offer a range of research opportunities, although we did observe some differences in topic prevalence. These differences could be due to the nature of some types of research (e.g., research that requires an in-person presence) or differences in research intensity between programs (e.g., amount of grant funding or proximity to a medical center). Future research should explore why research topic prevalence may vary by program delivery. We hope that this text-mining application serves as an illustrative example for researchers considering how to draw inferences from large sets of text documents. We are particularly interested in seeing future work that might combine traditional qualitative approaches and large-scale text mining to leverage the advantages of each.
Serum Ascorbic Acid and Thiamine Concentrations in Sepsis: Secondary Analysis of the Swiss Pediatric Sepsis Study
Authors: Equey Lucile , Agyeman Philipp K. A. , Veraguth Rosemarie , Rezzi Serge , Schlapbach Luregn J. , Giannoni Eric ,   for the Swiss Pediatric Sepsis Study Group
Published: May 2022

OBJECTIVES:

To determine circulating levels of ascorbic acid (VitC) and thiamine (VitB1) in neonates and children with blood culture-proven sepsis.

DESIGN:

Nested single-center study of neonates and children prospectively included in the Swiss Pediatric Sepsis Study.

SETTING:

One tertiary care academic hospital.

PATIENTS:

Sixty-one neonates and children 0–16 years old.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

VitC and VitB1 were quantified in serum of patients (median age, 10.5 mo; interquartile range [IQR], 0.5–62.1 mo) with blood culture-proven sepsis. Median time between sepsis onset and sampling for measurement of vitamins was 3 days (IQR, 2–4 d). Median serum levels of VitC and VitB1 were 32.4 μmol/L (18.9–53.3 μmol/L) and 22.5 nmol/L (12.6–82 nmol/L); 36% of the patients (22/61) had low VitC and 10% (6/61) had VitC deficiency; and 72% (44/61) had low VitB1 and 13% (8/61) had VitB1 deficiency. Children with low VitC were older (p = 0.007) and had higher C-reactive protein (p = 0.004) compared with children with VitC within the normal range. Children with low VitB1 levels were older (p = 0.0009) and were less frequently receiving enteral or parenteral vitamin supplementation (p = 0.0000003) compared with children with normal VitB1 levels.

CONCLUSIONS:

In this cohort of newborns and children with sepsis, low and deficient VitC and VitB1 levels were frequently observed. Age, systemic inflammation, and vitamin supplementation were associated with vitamin levels during sepsis.
Vitamin C Deficiency in Critically Ill Children: Prospective Observational Cohort Study
Authors: Fathi Alireza , Downey Corcoran , Rabiee Gohar Aida
Published: May 2022

OBJECTIVES:

To evaluate the presence of vitamin C deficiency in critically ill children admitted to the PICU.

DESIGN:

Single-center prospective observational cohort study.

SETTING:

A 28-bed PICU and a pediatric outpatient sedation room of a tertiary-care teaching hospital.

PATIENTS:

Two pediatric patient groups 0–21 years old were studied: a PICU group and a group receiving deep sedation for elective outpatient procedures (noncritical care group).

INTERVENTIONS:

Vitamin C level was drawn for the PICU group within 24 hours of admission. Vitamin C level was drawn prior to start of deep sedation for the noncritical group.

Measurement and Main Results:

Vitamin C deficiency was present in 11/60 (18%) in the PICU group and 0/21 (0%) of the noncritical group (p < 0.05).

CONCLUSIONS:

Vitamin C deficiency was prevalent in our patients admitted to PICU.
Semiautomated Regional Citrate Anticoagulation for Continuous Kidney Replacement Therapy: An Observational Study in Young Children
Authors: Liet Jean-Michel , Baleine Julien , Demaret Pierre , Mounier Sophie , Porcheret Florence , Joram Nicolas , Chenouard Alexis
Published: May 2022

OBJECTIVES:

To review use of semiautomated regional citrate anticoagulation (saRCA) for continuous kidney replacement therapy (CKRT) in young children.

DESIGN:

Retrospective cohort study.

SETTING:

Three independent PICUs.

PATIENTS:

All consecutive children weighing less than 11 kg who received CKRT with saRCA from January 2015 to June 2020.

INTERVENTIONS:

None.

MEASUREMENTS and MAIN RESULTS:

Twenty-one children weighing less than 11 kg underwent CKRT with saRCA. The total duration of the CKRT was 2,014 hours, with a total of 64 CKRT sessions. Citrate intoxication occurred in four of 64 CKRT sessions (6%). Citrate intoxication was consistently observed in the few CKRT sessions where the initial lactate concentration was greater than 4 mmol/L or the ratio of replacement fluid flow to citrate flow less than 50%. The rate of unscheduled interruptions of CKRT sessions was 25% (16/64).

CONCLUSIONS:

We have used saRCA for CKRT in children weighing less than 11 kg. A strict protocol and intensive training are required to minimize complications.
Long-term effectiveness and safety of medical cannabis administered through the metered-dose Syqe Inhaler
Authors: Aviram Joshua , Atzmony Daniella , Eisenberg Elon
Published: May 2022

Introduction:

Preliminary clinical studies on medical cannabis (MC) treatment using the Syqe Inhaler showed short-term effectiveness and safety at very low and precise doses of MC.

Objectives:

Here, we retrospectively analyzed “real-life” long-term data collected in real time on the potential effectiveness and safety of MC administered with this device.

Methods:

Patients were monitored by Syqe's patient support program. (−)-Δ9-trans-Tetrahydrocannabinol (Δ9-THC) served as a dosage marker for full-spectrum MC. Pain intensity was evaluated using a numeric pain scale (NPS) from baseline to 120 days after treatment initiation. The change in quality of life (QoL) from baseline was evaluated. Adverse events (AEs) were followed up continuously for 15 months.

Results:

Of the 143 patients (mean age 62 ± 17 years; 54% males) included in the analysis, most (72%) were diagnosed with chronic neuropathic pain. The stable daily dose, after a mean 26 ± 10 days of titration was 1,500 ± 688 μg aerosolized Δ9-THC. Significant pain reduction, ranging from 22.8% in the intent-to-treat population to 28.4% in the population that reported baseline pain intensity ≥8 points on the NPS (P < 0.001), was observed. Ninety-two percent of patients reported improved QoL. Adverse events were reported mostly during the titration phase (34% of patients) and declined to ≤4% at 3 to 15 months. Only 7% of patients reported psychoactive AEs (anxiety and restlessness).

Conclusions:

Medical cannabis treatment with the Syqe Inhaler demonstrated overall long-term pain reduction, QoL improvement, and a superior AE profile compared with administration of MC by conventional routes. Additional follow-up in a larger population is warranted.
MicroRNA-136-5p from Endothelial Progenitor Cells-released Extracellular Vesicles Mediates TXNIP to Promote the Dissolution of Deep Venous Thrombosis
Authors: Feng Yaping , Lei Bo , Zhang Huan , Niu Luyuan , Li Xiangtao , Luo Xiaoyun , Zhang Fuxian
Published: May 2022

Objective:

Endothelial progenitor cells-released extracellular vesicles (EPCs-EVs) have previously been reported to promote the dissolution of deep venous thrombosis (DVT) through delivery of microRNA (miR). Given that, this research was projected to search the relative action of EPCs-EVs transferring of miR-136-5p in DVT.

Methods:

From EPCs transfected with miR-136-5p agomir or antagomir, EVs were extracted and then injected into DVT mice. Meanwhile, based on the treatment with EPCs-EVs loading miR-136-5p antagomir, silenced thioredoxin-interacting protein (TXNIP) lentivirus was injected into DVT mice to perform the rescue experiments. Afterwards, the length and weight of venous thrombosis, EPC apoptosis and inflammatory factors, plasmin, fibrinogen, and thrombin-antithrombin were measured. miR-136-5p and TXNIP expression in DVT mice, and their targeting relationship were evaluated.

Results:

miR-136-5p expression was suppressed and TXNIP expression was elevated in DVT mice. EPCs-EV reduced the length and weight of venous thrombosis, suppressed cell apoptosis and inflammatory reaction, as well as elevated level of plasmin, and reduced levels of fibrinogen and thrombin-antithrombin in DVT mice. Restored miR-136-5p loaded by EPCs-EV further attenuated DVT but EPCs-EV transfer of depleted miR-136-5p resulted in the opposite consequences. miR-136-5p targeted TXNIP and silenced TXNIP rescued the effect of EPCs-EV transfer of depleted miR-136-5p on DVT.

Conclusion:

miR-136-5p from EPCs-EV suppresses TXNIP expression to reduce the thrombus size in DVT, offering a promising treatment target for DVT
A Comprehensive Appraisal of Risk Prediction Models for Cardiogenic Shock
Authors: Bhat Anusha G. , van Diepen Sean , Katz Jason N. , Islam Ashequl , Tehrani Benham N. , Truesdell Alexander G. , Kapur Navin K. , Holmes David R. , Menon Venugopal , Jaber Wissam A. , Nicholson William J. , Zhao David X. , Vallabhajosyula Saraschandra
Published: May 2022

Despite advances in early revascularization, percutaneous hemodynamic support platforms, and systems of care, cardiogenic shock (CS) remains associated with a mortality rate higher than 50%. Several risk stratification models have been derived since the 1990 s to identify patients at high risk of adverse outcomes. Still, limited information is available on the differences between scoring systems and their relative applicability to both acute myocardial infarction and advanced decompensated heart failure CS. Thus, we reviewed the similarities, differences, and limitations of published CS risk prediction models and herein discuss their suitability to the contemporary management of CS care.
Inflammasome-related Markers upon ICU Admission do not Correlate with Outcome in Critically Ill COVID-19 Patients
Authors: Adamik Barbara , Ambrożek-Latecka Magdalena , Dragan Barbara , Jeznach Aldona , Śmiechowicz Jakub , Gożdzik Waldemar , Skirecki Tomasz
Published: May 2022

Purpose:

The development of targeted biological therapies for coronavirus disease 2019 (COVID-19) requires reliable biomarkers that could help indicate how patients are responding. The hyperactivation of inflammasomes by the SARS-CoV2 virus is hypothesized to contribute to a more severe course of the COVID-19 disease. Therefore, we aimed to evaluate the prognostic value of several inflammasome-related cytokines and proteins upon admission to the intensive care unit (ICU).

Patients and Methods:

We performed a prospective cohort study. Plasma samples were obtained from 45 critically ill COVID-19 patients and 10 patients without any signs of infection (traumatic brain injury [TBI]) on admission to the ICU. Concentrations of IL-1a, IL-1β, IL-18, IL-1RA, galectin-1, apoptosis-associated speck-like proteins, LDH, ferritin, and gasdermin D were analyzed. A cell-free caspase-1 plasma assay was done by inhibitor-based immunoprecipitation followed by a Western Blot. Demographic and clinical characteristics were recorded.

Results:

Inhospital mortality in COVID-19 patients was 62%. Galectin-1 was 1.8-fold lower in COVID-19 than in TBI patients (17101.84 pg/mL vs. 30764.20 pg/mL, P = 0.007), but other inflammasome-related biomarkers had similar concentrations. Patients with a Sequential Organ Failure Assessment (SOFA) score of > 9 on admission who were at high risk of death had significantly higher galectin-1 but lower IL-1RA in comparison with low-risk patients (25551.3 pg/mL vs. 16302.7 pg/mL, P = 0.014; 14.5 pg/mL vs. 39.4pg/mL, P = 0.04, respectively). Statistically significant correlations were observed between: IL-1a and platelets (r = –0.37), IL-1 β and platelets (r = –0.36), ferritin and INR (r = 0.39). Activated caspase-1 p35, whose presence was related to higher fibrinogen and lower D-dimers, was detected in 12 out of 22 COVID-19 patients and in none of the TBI patients. Moreover, densitometric analysis showed a significantly higher amount of p35 in patients with a SOFA score > 9.

Conclusion:

We found that the systemic markers of activation of inflammasomes in critically ill COVID-19 patients were not directly related to outcome. Therefore, potential interventions aimed at the inflammasome pathway in this group of patients may be of limited effectiveness and should be biomarker-guided.
Nano-chemically Modified Tetracycline-3 (nCMT-3) Attenuates Acute Lung Injury via Blocking sTREM-1 Release and NLRP3 Inflammasome Activation
Authors: Meng Qinghe , Wang Xiaojing , Guo Dandan , Shi Changying , Gu Raymond , Ma Julia , Nieman Gary , Kollisch-Singule Michaela , Luo Juntao , Cooney Robert N.
Published: May 2022

Background:

Intratracheal (IT) lipopolysaccharide (LPS) causes severe acute lung injury (ALI) and systemic inflammation. CMT-3 has pleiotropic anti-inflammatory effects including matrix metalloproteinase (MMP) inhibition, attenuation of neutrophil (PMN) activation, and elastase release. CMT-3's poor water solubility limits its bioavailability when administered orally for treating ALI. We developed a nano-formulation of CMT-3 (nCMT-3) to test the hypothesis that the pleiotropic anti-inflammatory activities of IT nCMT-3 can attenuate LPS-induced ALI.

Methods:

C57BL/6 mice were treated with aerosolized IT nCMT-3 or saline, then had IT LPS or saline administered 2 h later. Tissues were harvested at 24 h. The effects of LPS and nCMT-3 on ALI were assessed by lung histology, MMP level/activity (zymography), NLRP3 protein, and activated caspase-1 levels. Blood and bronchoalveolar lavage fluid (BALF) cell counts, PMN elastase, and soluble triggering receptor expressed on myelocytes-1 (sTREM-1) levels, TNF-α, IL-1β, IL-6, IL-18, and BALF protein levels were also measured.

Results:

LPS-induced ALI was characterized by histologic lung injury (PMN infiltration, alveolar thickening, edema, and consolidation) elevated proMMP-2, -9 levels and activity, increased NLRP-3 protein and activated caspase-1 levels in lung tissue. LPS-induced increases in plasma and BALF levels of sTREM-1, TNF-α, IL-1β, IL-6, IL-18, PMN elastase and BALF protein levels demonstrate significant lung/systemic inflammation and capillary leak. nCMT-3 significantly ameliorated all of these LPS-induced inflammatory markers to control levels, and decreased the incidence of ALI.

Conclusions:

Pre-treatment with nCMT3 significantly attenuates LPS-induced lung injury/inflammation by multiple mechanisms including: MMP activation, PMN elastase, sTREM-1 release, and NLRP3 inflammasome/caspase-1 activation.
Laparoscopic Management of Spontaneous Colonic Perforation: A Single Institution Study of 52 Patients
Authors: Li Sen , Zheng Kan , Yu Kun , Li Wei , Si Xianke , Zhang Jixun , Wu Wentao , Cao Yijun , Yang Jiahua
Published: May 2022

Background:

Spontaneous colonic perforation (SCP) is associated with an devastating result. The use of laparoscopy for SCP remains controversial. This study aimed to compare the postoperative outcomes of patients who received either laparoscopic or open surgery and to evaluate the efficacy of laparoscopic surgery and the risk factors affecting prognosis.

Patients and Methods:

A retrospective study of patients who underwent surgery for SCP from January 2005 to December 2020 was performed. Demographic data, intraoperative variables, length of stay, and surgical complications were retrieved.

Results:

A total of 52 patients were postoperatively diagnosed with SCP. Thirty (57.69%) procedures were performed using laparoscopic surgery (group A) and 22 (42.31%) were performed using open surgery (group B). There were no significant differences between groups A and B in terms of age, sex, chronic concomitant disease, chronic constipation, incentives, imaging findings, preoperative diagnosis, American Society of Anesthesiologists (ASA) score, Mannheim Peritonitis Index (MPI), operation time, days to resumption of liquids, site of perforation, surgical procedures, or types of perforation (P>0.05). The incidence of wound infection in group A was significantly lower than that in group B (P<0.05), but there was no significant difference in the incidence of abdominal abscess between the 2 groups (P>0.05). Significant differences were found in days to start walking and days to resumption of solids between the 2 groups (P<0.05). Group B had a longer length of hospital stay than group A (P<0.05). After multivariate analysis, the independent variables associated with worse perioperative complications were an age of 65 years and older, an ASA score of ≥3, and an MPI of >26.

Conclusions:

The prognosis of SCP is poor. The operation should follow principles that are simple, rapid, and effective. If there are no contraindications, laparoscopy may be the preferred method. Hartmann procedure is a promising surgical strategy. The age, ASA score, and MPI may indicate the severity and prognosis of SCP.
Valproic acid during hypotensive resuscitation in pigs with trauma and hemorrhagic shock does not improve survival
Authors: Martini Wenjun Z. , Xia Hui , Ryan Kathy L. , Bynum James , Cap Andrew P.
Published: May 2022

BACKGROUND

Valproic acid (VPA) has been extensively used for treatment of anxiety and seizure. Recent studies have shown that VPA has cellular protective effects in preclinical models following severe hemorrhage. This study investigated the effects of VPA on coagulation and survival in pigs after traumatic hemorrhage and hypotensive resuscitation.

METHODS

Following baseline measurements, femur fracture was performed in 20 anesthetized and instrumented pigs (41 ± 2 kg), followed by hemorrhage of 55% of the estimated blood volume and a 10-minute shock period. Pigs were then resuscitated for 30 minutes with normal saline (NS) alone (NS group, n = 10, 4 mL/kg) or VPA solution (VPA group, n = 10, 90 mg/kg, 2 mL/kg of 45 mg VPA/mL, plus 2 mL NS/kg). All pigs were then monitored for 2 hours or until death. Hemodynamics were recorded, and blood samples were taken for blood and coagulation analysis (Rotem) at baseline, after hemorrhage, resuscitation, and 2 hours or death.

RESULTS

Femur fracture and hemorrhage caused similar reductions in mean arterial pressure and cardiac output, and increase in heart rate in both groups. Resuscitation with NS or VPA did not return these measurements to baseline. No differences were observed in hematocrit, pH, lactate, base excess, or total protein between the groups. Compared with NS, resuscitation with VPA decreased platelet counts and prolonged activated partial thromboplastin time, with no differences in fibrinogen levels, prothrombin time, or any of the Rotem measurements between the two groups. Neither survival rates (NS, 7 of 10 pigs; VPA, 7 of 10 pigs) nor survival times after resuscitation (NS, 97 ± 40 minutes; VPA, 98 ± 43 minutes) differed between the groups.

CONCLUSION

Following traumatic hemorrhage and hypotensive resuscitation in pigs, VPA provides no benefit toward improving coagulation function or survival times.
Phase-change-mediated transport and agglomeration of fungal spores on wheat awns
Authors: Iliff Grady J. , Mukherjee Ranit , Gruszewski Hope A. , Schmale III David G. , Jung Sunghwan , Boreyko Jonathan B.
Published: May 2022

Wheat and other staple crops are devastated by fungal diseases. Many fungal plant pathogens are spread via active or passive discharge of microscopic spores. Here, we described the unique transport of spores of the fungal pathogen
Epicoccum tritici
, causal agent of black sooty mould, on wheat awns. The unique multi-scale architecture of wheat awns, coupled with condensation and evaporation of dew droplets, facilitated the transport and agglomeration of spores of the fungus. First, dew droplets spontaneously transported spores from the tips of awn hairs to the neighbouring stomatal ridges, driven by gradients in Laplace pressure and surface wettability. Subsequently, spores agglomerated into dry clusters due to the Cheerios effect and evaporation, increasing the likelihood of passive spore removal via wind shear and/or rainsplash. Future plant breeding approaches should consider the development of modified spike structures, such as those without awns or awn hairs, to reduce the potential for spread of fungal plant pathogens.
The role of time-varying viral shedding in modelling environmental surveillance for public health: revisiting the 2013 poliovirus outbreak in Israel
Authors: Brouwer Andrew F. , Eisenberg Marisa C. , Shulman Lester M. , Famulare Michael , Koopman James S. , Kroiss Steve J. , Hindiyeh Musa , Manor Yossi , Grotto Itamar , Eisenberg Joseph N. S.
Published: May 2022

Environmental pathogen surveillance is a sensitive tool that can detect early-stage outbreaks, and it is being used to track poliovirus and other pathogens. However, interpretation of longitudinal environmental surveillance signals is difficult because the relationship between infection incidence and viral load in wastewater depends on time-varying shedding intensity. We developed a mathematical model of time-varying poliovirus shedding intensity consistent with expert opinion across a range of immunization states. Incorporating this shedding model into an infectious disease transmission model, we analysed quantitative, polymerase chain reaction data from seven sites during the 2013 Israeli poliovirus outbreak. Compared to a constant shedding model, our time-varying shedding model estimated a slower peak (four weeks later), with more of the population reached by a vaccination campaign before infection and a lower cumulative incidence. We also estimated the population shed virus for an average of 29 days (95% CI 28–31), longer than expert opinion had suggested for a population that was purported to have received three or more inactivated polio vaccine (IPV) doses. One explanation is that IPV may not substantially affect shedding duration. Using realistic models of time-varying shedding coupled with longitudinal environmental surveillance may improve our understanding of outbreak dynamics of poliovirus, SARS-CoV-2, or other pathogens.
Distinct forms of resonant optimality within insect indirect flight motors
Authors: Pons Arion , Beatus Tsevi
Published: May 2022

Insect flight motors are extraordinary natural structures that operate efficiently at high frequencies. Structural resonance is thought to play a role in ensuring efficient motor operation, but the details of this role are elusive. While the efficiency benefits associated with resonance may be significant, a range of counterintuitive behaviours are observed. In particular, the relationship between insect wingbeat frequencies and thoracic natural frequencies is uncertain, with insects showing wingbeat frequency modulation over both short and long time scales. Here, we offer new explanations for this modulation. We show how, in linear and nonlinear models of an indirect flight motor, resonance is not a unitary state at a single frequency, but a complex cluster of distinct and mutually exclusive states, each representing a different form of resonant optimality. Additionally, by characterizing the relationship between resonance and the state of negative work absorption within the motor, we demonstrate how near-perfect resonant energetic optimality can be maintained over significant wingbeat frequency ranges. Our analysis leads to a new conceptual model of flight motor operation: one in which insects are not energetically restricted to a precise wingbeat frequency, but instead are robust to changes in thoracic and environmental properties—an illustration of the extraordinary robustness of these natural motors.
Phagocytosis of exogenous bacteria by gill epithelial cells in the deep-sea symbiotic mussel
Bathymodiolus japonicus
Authors: Tame Akihiro , Maruyama Tadashi , Yoshida Takao
Published: May 2022

Animals that live in nutrient-poor environments, such as the deep sea, often establish intracellular symbiosis with beneficial bacteria that provide the host with nutrients that are usually inaccessible to them. The deep-sea mussel
Bathymodiolus japonicus
relies on nutrients from the methane-oxidizing bacteria harboured in epithelial gill cells called bacteriocytes. These symbionts are specific to the host and transmitted horizontally, being acquired from the environment by each generation. Morphological studies in mussels have reported that the host gill cells acquire the symbionts via phagocytosis, a process that facilitates the engulfment and digestion of exogenous microorganisms. However, gill cell phagocytosis has not been well studied, and whether mussels discriminate between the symbionts and other bacteria in the phagocytic process remains unknown. Herein, we aimed to investigate the phagocytic ability of gill cells involved in the acquisition of symbionts by exposing the mussel to several types of bacteria. The gill cells engulfed exogenous bacteria from the environment indiscriminately. These bacteria were preferentially eliminated through intracellular digestion using enzymes; however, most symbionts were retained in the bacteriocytes without digestion. Our findings suggest that regulation of the phagocytic process after engulfment is a key mechanism for the selection of symbionts for establishing intracellular symbiosis.