bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sympathetic dysregulation induced by postnatal intermittent hypoxia
Authors: Karlen-Amarante Marlusa , Leirão Isabela P , Katayama Pedro L , Colombari Eduardo , Bittencourt-Silva Paloma G , Menezes Miguel F , Zoccal Daniel B 
Published: March 2023

Abstract

Study Objectives
Exposure to postnatal chronic intermittent hypoxia (pCIH), as experienced in sleep-disordered breathing, is a risk factor for developing cardiorespiratory diseases in adulthood. pCIH causes respiratory instability and motor dysfunction that persist until adult life. In this study, we investigated the impact of pCIH on the sympathetic control of arterial pressure in rats.

Methods and Results
Neonate male Holtzman rats (P0–1) were exposed to pCIH (6% O2 for 30 seconds, every 10 minutes, 8 h/day) during their first 10–15 days of life, while control animals were maintained under normoxia. In early adult life (P25–40), freely behaving pCIH animals (n = 13) showed higher baseline arterial pressure levels linked to augmented sympathetic-mediated variability than control animals (n = 12, p &lt; 0.05). Using decerebrated in situ preparations, we found that juvenile pCIH rats exhibited a twofold increase in thoracic sympathetic nerve activity (n = 14) and elevated firing frequency of ventromedullary presympathetic neurons (n = 7) compared to control rats (n = 6–7, p &lt; 0.05). This pCIH-induced sympathetic dysregulation was associated with increased HIF-1α (hypoxia-inducible factor 1 alpha) mRNA expression in catecholaminergic presympathetic neurons (n = 5, p &lt; 0.05). At older age (P90–99), pCIH rats displayed higher arterial pressure levels and larger depressor responses to ganglionic blockade (n = 6–8, p &lt; 0.05), confirming the sympathetic overactivity state.

Conclusions
pCIH facilitates the vasoconstrictor sympathetic drive by mechanisms associated with enhanced firing activity and HIF-1α expression in ventromedullary presympathetic neurons. This excessive sympathetic activity persists until adulthood resulting in high blood pressure levels and variability, which contribute to developing cardiovascular diseases.
Solriamfetol improves chronic sleep fragmentation-induced increases in sleep propensity and ameliorates explicit memory in male mice
Authors: Puech Clementine , Badran Mohammad , Barrow Max B , Runion Alexandra R , Gozal David 
Published: March 2023

Abstract
Obstructive sleep apnea (OSA) is a highly prevalent condition characterized by episodes of partial or complete breath cessation during sleep that induces sleep fragmentation (SF). One of the frequent manifestations of OSA is the presence of excessive daytime sleepiness (EDS) associated with cognitive deficits. Solriamfetol (SOL) and modafinil (MOD) are wake-promoting agents commonly prescribed to improve wakefulness in OSA patients with EDS. This study aimed to assess the effects of SOL and MOD in a murine model of OSA characterized by periodic SF. Male C57Bl/6J mice were exposed to either control sleep (SC) or SF (mimicking OSA) during the light period (06:00 h to 18:00 h) for 4 weeks, which consistently induces sustained excessive sleepiness during the dark phase. Both groups were then randomly assigned to receive once-daily intraperitoneal injections of SOL (200 mg/kg), MOD (200 mg/kg), or vehicle for 1 week while continuing exposures to SF or SC. Sleep/wake activity and sleep propensity were assessed during the dark phase. Novel Object Recognition test, Elevated-Plus Maze Test, and Forced Swim Test were performed before and after treatment. SOL or MOD decreased sleep propensity in SF, but only SOL induced improvements in explicit memory, while MOD exhibited increased anxiety behaviors. Chronic SF, a major hallmark of OSA, induces EDS in young adult mice that is mitigated by both SOL and MOD. SOL, but not MOD, significantly improves SF-induced cognitive deficits. Increased anxiety behaviors are apparent in MOD-treated mice. Further studies aiming to elucidate the beneficial cognitive effects of SOL are warranted.
Zika virus knowledge, attitudes and prevention behaviors among pregnant women in the ZEN cohort study, Colombia, 2017–2018
Authors: Burkel Veronica K , Newton Suzanne M , Acosta Jacqueline , Valencia Diana , Benavides Monica , Tong Van T , Daza Marcela , Sancken Christina , Gonzalez Maritza , Polen Kara , Rodriguez Helena , Borbón Milena , Rao Carol Y , Gilboa Suzanne M , Honein Margaret A , Ospina Marta L , Johnson Candice Y 
Published: March 2023

ABSTRACT

Background
Zika virus (ZIKV) infection during pregnancy can cause severe birth defects in the fetus and is associated with neurodevelopmental abnormalities in childhood. Our objective was to describe ZIKV knowledge and attitudes among pregnant women in Colombia while ZIKV was circulating and whether they predicted the adoption of behaviors to prevent ZIKV mosquito-borne and sexual transmission.

Methods
We used self-reported data from Zika en Embarazadas y Niños (ZEN), a cohort study of women in early pregnancy across three regions of Colombia during 2017–2018. We used Poisson regression to estimate associations between knowledge, attitudes and previous experience with mosquito-borne infection and preventative behaviors.

Results
Among 1519 women, knowledge of mosquito-borne transmission was high (1480; 97.8%) and 1275 (85.5%) participants were worried about ZIKV infection during pregnancy. The most common preventive behavior was wearing long pants (1355; 89.4%). Regular mosquito repellent use was uncommon (257; 17.0%). While ZIKV knowledge and attitudes were not associated with the adoption of ZIKV prevention behaviors, previous mosquito-borne infection was associated with increased condom use (prevalence ratio 1.4, 95% CI 1.1 to 1.7).

Conclusions
Participants were well informed about ZIKV transmission and its health consequences. However, whether this knowledge resulted in behavior change is less certain.
Altering Specificity and Autoactivity of Plant Immune Receptors Sr33 and Sr50 Via a Rational Engineering Approach
Authors: Tamborski Janina , Seong Kyungyong , Liu Furong , Staskawicz Brian J. , Krasileva Ksenia V. 
Published: March 2023

Many resistance genes deployed against pathogens in crops are intracellular nucleotide-binding (NB) leucine-rich repeat (LRR) receptors (NLRs). The ability to rationally engineer the specificity of NLRs will be crucial in the response to newly emerging crop diseases. Successful attempts to modify NLR recognition have been limited to untargeted approaches or depended on previously available structural information or knowledge of pathogen-effector targets. However, this information is not available for most NLR-effector pairs. Here, we demonstrate the precise prediction and subsequent transfer of residues involved in effector recognition between two closely related NLRs without their experimentally determined structure or detailed knowledge about their pathogen effector targets. By combining phylogenetics, allele diversity analysis, and structural modeling, we successfully predicted residues mediating interaction of Sr50 with its cognate effector AvrSr50 and transferred recognition specificity of Sr50 to the closely related NLR Sr33. We created synthetic versions of Sr33 that contain amino acids from Sr50, including Sr33syn, which gained the ability to recognize AvrSr50 with 12 amino-acid substitutions. Furthermore, we discovered that sites in the LRR domain needed to transfer recognition specificity to Sr33 also influence autoactivity in Sr50. Structural modeling suggests these residues interact with a part of the NB-ARC domain, which we named the NB-ARC latch, to possibly maintain the inactive state of the receptor. Our approach demonstrates rational modifications of NLRs, which could be useful to enhance existing elite crop germplasm. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Low-dose Initiation of Buprenorphine in Hospitalized Patients Using Buccal Buprenorphine: A Case Series
Authors: Adams Kathleen K. , Cohen Shawn M. , Guerra Michael E. , Weimer Melissa B. 
Published: March 2023

Objective
To describe a low-dose buprenorphine initiation strategy with buccal buprenorphine.

Methods
This is a case series of hospitalized patients with opioid use disorder (OUD) and/or chronic pain who underwent low-dose buprenorphine initiation with buccal buprenorphine to sublingual buprenorphine. Results are descriptively reported.

Results
Forty-five patients underwent low-dose buprenorphine initiation from January 2020 to July 2021. Twenty-two (49%) patients had OUD only, 5 (11%) patients had chronic pain only, and 18 (40%) patients had both OUD and chronic pain. Thirty-six (80%) patients had documented history of heroin or non-prescribed fentanyl use before admission. Acute pain in 34 (76%) patients was the most commonly documented rationale for low-dose buprenorphine initiation. Methadone was the most common outpatient opioid utilized before admission (53%). The addiction medicine service consulted on 44 (98%) cases and median length of stay was approximately 2 weeks. Thirty-six (80%) patients completed the transition to sublingual buprenorphine with a median completion dose of 16 mg daily. Of the 24 patients (53%) with consistently documented Clinical Opiate Withdrawal Scale scores, no patients experienced severe opioid withdrawal. Fifteen (62.5%) experienced mild or moderate withdrawal and 9 (37.5%) experienced no withdrawal (Clinical Opiate Withdrawal Scale score <5) during the entire process. Continuity of postdischarge prescription refills ranged from 0 to 37 weeks and the median number of buprenorphine refills was 7 weeks.

Conclusions
Low-dose buprenorphine initiation with buccal buprenorphine to sublingual buprenorphine was well tolerated and can be safely and effectively utilized for patients whose clinical scenario precludes traditional buprenorphine initiation strategies.
Operative Fractures of the Phalangeal Head and Neck in Children—Does Open Reduction Affect Outcomes?
Authors: Vaslow Aaron S. , Deal James Banks , Ho Christine A. 
Published: March 2023

Background:
Closed reduction percutaneous pinning of displaced pediatric phalangeal head and neck fractures is preferred to prevent malunion and loss of motion and function. However, open reduction is required for irreducible fractures and open injuries. We hypothesize that osteonecrosis is more common in open injuries than closed injuries that require either open reduction or closed reduction percutaneous pinning.

Methods:
Retrospective chart review of 165 phalangeal head and neck fractures treated surgically with pin fixation at a single tertiary pediatric trauma center from 2007 to 2017. Fractures were stratified as open injuries (OI), closed injuries undergoing open reduction (COR), or closed injuries treated with closed reduction (CCR). The groups were compared using Pearson χ2 tests and ANOVA. Two group comparisons were made with Student t test.

Results:
There were 17 OI fractures, 14 COR fractures, and 136 CCR fractures. Crush injury was the predominant mechanism in OI versus COR and CCR groups. The average time from injury to surgery was 1.6 days for OI, 20.4 days for COR, and 10.4 days for CCR. The average follow-up was 86.5 days (range, 0 to 1204). The osteonecrosis rate differed between the OI versus COR and OI versus CCR groups (71% for OI, 7.1% for COR, and 1.5% for CCR). Rates of coronal malangulation >15 degrees differed between the OI and COR or CCR groups, but the 2 closed groups did not differ. Outcomes were defined using Al-Qattan’s system; CCR had the most excellent and fewest poor outcomes. One OI patient underwent partial finger amputation. One CCR patient had rotational malunion but declined derotational osteotomy.

Conclusions:
Open phalangeal head and neck fractures have more concomitant digital injuries and postoperative complications compared with injuries closed on presentation, regardless of whether the fracture underwent open or closed reduction. Although osteonecrosis occurred in all 3 cohorts, it was most frequent in open injuries. This study allows surgeons to discuss rates of osteonecrosis and resultant complications with families whose child presents with phalangeal head and neck fractures that are indicated for surgical treatment.

Level of Evidence:
Therapeutic, Level III.
Update on Chemoresistance Mechanisms to First-Line Chemotherapy for Gallbladder Cancer and Potential Reversal Strategies
Authors: Lai Jinbao , Yang Songlin , Lin Zhuying , Huang Wenwen , Li Xiao , Li Ruhong , Tan Jing , Wang Wenju 
Published: March 2023

Objective:
Gallbladder cancer (GBC) mortality remains high and chemoresistance is increasing. This review consolidates what is known about the mechanisms of chemoresistance to inform and accelerate the development of novel GBC-specific chemotherapies.

Methods:
Studies related to GBC-related chemoresistance were systematically screened in PubMed using the advanced search function. Search terms included GBC, chemotherapy, and signaling pathway.

Results:
Analysis of existing studies showed that GBC has poor sensitivity to cisplatin, gemcitabine (GEM), and 5-fluorouracil. DNA damage repair-related proteins, including CHK1, V-SCR, and H2AX, are involved in tumor adaptation to drugs. GBC-specific chemoresistance is often accompanied by changes in the apoptosis and autophagy-related molecules, BCL-2, CRT, and GBCDRlnc1. CD44+ and CD133+ GBC cells are less resistant to GEM, indicating that tumor stem cells are also involved in chemoresistance. In addition, glucose metabolism, fat synthesis, and glutathione metabolism can influence the development of drug resistance. Finally, chemosensitizers such as lovastatin, tamoxifen, chloroquine, and verapamil are able improve the therapeutic effect of cisplatin or GEM in GBC.

Conclusions:
This review summarizes recent experimental and clinical studies of the molecular mechanisms of chemoresistance, including autophagy, DNA damage, tumor stem cells, mitochondrial function, and metabolism, in GBC. Information on potential chemosensitizers is also discussed. The proposed strategies to reverse chemoresistance should inform the clinical use of chemosensitizers and gene-based targeted therapy for this disease.
Do published trial results influence physician prescribing patterns? Intravitreal antivascular endothelial growth factor usage by the United States Ophthalmologists before and after Protocol T study
Authors: Shah Serena , Markatia Zahra , Watane Arjun , Feldman Alexandra , Shah Lea , Sridhar Jayanth 
Published: March 2023

Purpose of review
Clinical trial publications may influence physician prescribing patterns. The Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol T study, published in 2015, examined outcomes of intravitreal antivascular endothelial growth factor (VEGF) medications for treatment of diabetic macular oedema (DME). This study investigates if the Protocol T 1-year results were associated with changes in prescribing patterns.

Recent findings
Anti-VEGF agents have revolutionized treatment of DME by blocking angiogenesis signalled by VEGF. Three commonly used anti-VEGF agents are on-label aflibercept (Eylea, Regeneron) and ranibizumab (Lucentis, Genentech) and off-label bevacizumab (Avastin, Genentech).

Summary
From 2013 to 2018, there was a significant positive trend in the average number of aflibercept injections for any indication (P < 0.002). There was no significant trend in the average number of bevacizumab (P = 0.09) and ranibizumab (P = 0.43) for any indication. The mean proportion of aflibercept injections per provider per year was 0.181, 0.217, 0.311, 0.403, 0.419 and 0.427; each year-by-year comparison was significant (all P < 0.001), and the largest increase was in 2015, the year of publication of Protocol T 1-year results. These results imply and reinforce that clinical trial publications may have significant effects on ophthalmologist prescribing patterns.
Advancing Health Equity Through Graduate Forensic Nursing Education
Authors: Berishaj Kelly 
Published: March 2023

ABSTRACT
Social justice is a core value of nursing and is deeply rooted within forensic nursing. Forensic nurses are uniquely positioned to examine and address social determinants of health that contribute to victimization, lack of access to forensic nursing services, and inability to utilize resources and services aimed at restoring health after an injury or illness related to trauma or violence. To achieve this, forensic nursing capacity and expertise must be strengthened through robust education. A graduate, forensic nursing, program sought to address this educational need by integrating content related to social justice, health equity, health disparity, and social determinants of health throughout its specialty curriculum.
Evidence on postbiotics in infants and children
Authors: Szajewska Hania , Salminen Seppo 
Published: March 2023

Purpose of review
The aim is to provide updated information on the concept of postbiotics and recent data on the efficacy of postbiotics for the prevention and treatment of childhood diseases.

Recent findings
In line with a recently proposed consensus definition, a postbiotic is ‘a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host’. Although inanimate, postbiotics may exert health benefits. There are only limited data on infant formulas containing postbiotics, but they are well tolerated, support adequate growth and demonstrate no potential identifiable risks, although clinical benefits remain limited. Currently, there is only limited support for postbiotic use for treating diarrhoea and preventing common paediatric infectious diseases in young children. Given the limited evidence, sometimes with a high risk of bias, caution is justified. No data in older children and adolescents are available.

Summary
The consensus definition of postbiotics facilitates further research. As not all postbiotics are the same, the type of disease and specific postbiotic studied should be considered when choosing postbiotics for the prevention or treatment of childhood diseases. Additional studies are needed to assess disease conditions responsive to postbiotics. Mechanisms of action of postbiotics need to be evaluated and characterized.
Community acquired and hospital acquired AKI - two diseases divided by a common definition
Authors: Kumar Vivek , Jha Vivekanand 
Published: March 2023

Purpose of review
Acute kidney injury (AKI) is common across the world. AKI that is acquired in the community (community acquired AKI, CA-AKI) has different risk factors, epidemiological profile, presentation and impact as compared to hospital acquired AKI (HA-AKI). Hence, similar approaches to tackle CA-AKI and HA-AKI might not work. This review highlights the important differences between the two entities that have a bearing on the overall approach to the conditions and how CA-AKI has been overshadowed by HA-AKI in research, diagnosis and treatment recommendations and clinical practice guidelines.

Recent findings
The overall burden of AKI is disproportionately more in low and low-middle income countries. The Global Snapshot study of International Society of Nephrology's (ISN) AKI 0by25 program has shown that CA-AKI is the dominant form in these settings. Its profile and outcomes vary with geographical and socio-economic characteristics of the regions where it develops. The current clinical practice guidelines for AKI align more with HA-AKI than CA-AKI, and fail to capture the complete spectrum of CA-AKI as well as its impact. The ISN AKI 0by25 studies have uncovered the circumstantial compulsions in defining and assessing AKI in these settings and shown feasibility of community-based interventions.

Summary
Efforts are needed to better understand CA-AKI in low-resource settings and develop context specific guidance and interventions. A multidisciplinary, collaborative approach with representation from community would be required.
The SARS-CoV-2 responsible for phlegmasia cerulea dolens: a case report
Authors: Banana Youssef , Bashir Husam , Boukabous Sara , Haddiya Intissar , Bentata Yassamine , Rezziki Abdellah , Benzirar Adnane , El Mahi Omar 
Published: March 2023

Introduction:
Coronavirus disease 2019 (COVID-19) is a worldwide pandemic systemic infection that is responsible for serious coagulopathies similar to disseminated intravascular coagulation.

Case Presentation:
The authors report the case of a COVID-19 patient who presented with phlegmasia cerulea dolens (PCD) of the left lower limb, so he benefited from aponeurotomies of the internal and anterolateral muscular compartments.

Clinical Discussion:
The severe acute respiratory syndrome coronavirus 2 involves an inflammatory process in thrombotic events in COVID-19 patients, including a cytokine storm. PCD evolves in three semiological phases: venous stasis, weakening of the pulses, and the constitution of major ischemia. In the literature, the authors find many reports that have been published regarding increased thrombus formation in COVID-19 patients; these include DVT formation, pulmonary embolism, and stroke. Nevertheless, publications concerning PCD in COVID-19 patients remain rare.

Conclusion:
Although the severe acute respiratory syndrome coronavirus 2 remains a thrombogenic pathology, systematic anticoagulation is the subject of hypothesis. Hence the importance of regular monitoring of markers of vascular thrombosis.
Spontaneous perforation of the common bile duct in adults presenting as biliary peritonitis: a case report and literature review
Authors: Bouzid Ahmed , Fendri Sami , Rejab Haitham , Trigui Ayman , Mejdoub Youssef , Boujelbene Salah 
Published: March 2023

Introduction:
Spontaneous perforation of the common bile duct (SPCBD) is an exceptional disease, especially in adults. The cause is often idiopathic once trauma and choledochal cyst are excluded. Early diagnosis is often difficult because of its often-misleading appearance.

Case presentation:
The authors report the case of a 54-year-old man, a known case of type 2 diabetes mellitus, who presented to our emergency department for acute abdominal pain that had evolved for 2 days.

Clinical findings and investigations:
On physical examination, the patient had a fever of up to 38.5°C, and the abdomen was distended and generally tight. The abdominal computerized tomography scan confirms the presence of free fluid. In addition, the thickness of the gallbladder wall had increased in contrast with a resolved gallbladder distention. Because exploration failed to demonstrate the cause of ascites, the authors performed a diagnostic paracentesis, which revealing ascites with a dark yellow-green color, which implied bile leakage.
After initial resuscitation, an emergent exploratory laparotomy was performed. The authors found biliary peritonitis secondary to SPCBD. After peritoneal lavage, the perforation was repaired over a T-tube. The postoperative course was uneventful. Histological findings were consistent with ulcerous acalculous cholecystitis. The patient was disease-free after a 3-month follow-up.

Discussion:
SPCBD is an uncommon condition in adults, and it is rarely reported in the literature. The pathogenesis of this disease is not clear and may be related to single or multiple factors. Usually, this disease is diagnosed in the postmortem. Early diagnosis and optimal surgical treatment are challenging.

Conclusion:
This present case highlighted the preoperative diagnostic difficulties of the SPCBD. Emergent surgical management should be instituted in the shortest time possible to reduce the high mortality.