bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of G-quadruplex structures in MALAT1 lncRNA that interact with nucleolin and nucleophosmin
Authors: Ghosh Arpita , Pandey Satya Prakash , Joshi Dheeraj Chandra , Rana Priya , Ansari Asgar Hussain , Sundar Jennifer Seematti , Singh Praveen , Khan Yasmeen , Ekka Mary Krishna , Chakraborty Debojyoti , Maiti Souvik
Published: August 2023

Nuclear-retained long non-coding RNAs (lncRNAs) including MALAT1 have emerged as critical regulators of many molecular processes including transcription, alternative splicing and chromatin organization. Here, we report the presence of three conserved and thermodynamically stable RNA G-quadruplexes (rG4s) located in the 3′ region of MALAT1. Using rG4 domain-specific RNA pull-down followed by mass spectrometry and RNA immunoprecipitation, we demonstrated that the MALAT1 rG4 structures are specifically bound by two nucleolar proteins, Nucleolin (NCL) and Nucleophosmin (NPM). Using imaging, we found that the MALAT1 rG4s facilitate the localization of both NCL and NPM to nuclear speckles, and specific G-to-A mutations that disrupt the rG4 structures compromised the localization of both NCL and NPM in speckles. In vitro biophysical studies established that a truncated version of NCL (ΔNCL) binds tightly to all three rG4s. Overall, our study revealed new rG4s within MALAT1, established that they are specifically recognized by NCL and NPM, and showed that disrupting the rG4s abolished localization of these proteins to nuclear speckles
Pot1b
−/− tumors activate G-quadruplex-induced DNA damage to promote telomere hyper-elongation
Authors: Takasugi Taylor , Gu Peili , Liang Fengshan , Staco Isabelle , Chang Sandy
Published: August 2023

Malignant cancers must activate telomere maintenance mechanisms to achieve replicative immortality. Mutations in the human Protection of Telomeres 1 (POT1) gene are frequently detected in cancers with abnormally long telomeres, suggesting that the loss of POT1 function disrupts the regulation of telomere length homeostasis to promote telomere elongation. However, our understanding of the mechanisms leading to elongated telomeres remains incomplete. The mouse genome encodes two POT1 proteins, POT1a and POT1b possessing separation of hPOT1 functions. We performed serial transplantation of Pot1b−/− sarcomas to better understand the role of POT1b in regulating telomere length maintenance. While early-generation Pot1b−/− sarcomas initially possessed shortened telomeres, late-generation Pot1b−/− cells display markedly hyper-elongated telomeres that were recognized as damaged DNA by the Replication Protein A (RPA) complex. The RPA-ATR-dependent DNA damage response at telomeres promotes telomerase recruitment to facilitate telomere hyper-elongation. POT1b, but not POT1a, was able to unfold G-quadruplex present in hyper-elongated telomeres to repress the DNA damage response. Our findings demonstrate that the repression of the RPA-ATR DDR is conserved between POT1b and human POT1, suggesting that similar mechanisms may underly the phenotypes observed in human cancers harboring human POT1 mutations.
Observing inhibition of the SARS-CoV-2 helicase at single-nucleotide resolution
Authors: Marx Sinduja K , Mickolajczyk Keith J , Craig Jonathan M , Thomas Christopher A , Pfeffer Akira M , Abell Sarah J , Carrasco Jessica D , Franzi Michaela C , Huang Jesse R , Kim Hwanhee C , Brinkerhoff Henry , Kapoor Tarun M , Gundlach Jens H , Laszlo Andrew H
Published: August 2023

The genome of SARS-CoV-2 encodes for a helicase (nsp13) that is essential for viral replication and highly conserved across related viruses, making it an attractive antiviral target. Here we use nanopore tweezers, a high-resolution single-molecule technique, to gain detailed insight into how nsp13 turns ATP-hydrolysis into directed motion along nucleic acid strands. We measured nsp13 both as it translocates along single-stranded DNA or unwinds double-stranded DNA. Our data reveal nsp13’s single-nucleotide steps, translocating at ∼1000 nt/s or unwinding at ∼100 bp/s. Nanopore tweezers’ high spatiotemporal resolution enables detailed kinetic analysis of nsp13 motion. As a proof-of-principle for inhibition studies, we observed nsp13’s motion in the presence of the ATPase inhibitor ATPγS. We construct a detailed picture of inhibition in which ATPγS has multiple mechanisms of inhibition. The dominant mechanism of inhibition depends on the application of assisting force. This lays the groundwork for future single-molecule inhibition studies with viral helicases.
Temporal patterns in taste sensitivity
Authors: Costanzo Andrew
Published: August 2023

Individuals vary in their ability to taste, and some individuals are more sensitive to certain tastes than others. Taste sensitivity is a predictor of various factors, such as diet, eating behavior, appetite regulation, and overall health. Furthermore, taste sensitivity can fluctuate within an individual over short to long periods of time: for example, in daily (diurnal) cycles, monthly (menstrual) cycles (in females), and yearly (seasonal) cycles. Understanding these temporal patterns is important for understanding individual eating habits and food preferences, particularly in the context of personalized and precision nutrition. This review provides a summary of the literature on taste sensitivity patterns across 3 temporal dimensions: daily, monthly, and yearly. Good evidence for diurnal patterns has been observed for sweet taste and fat taste, although the evidence is limited to rodent studies for the latter. Obese populations showed limited variation to sweet and fat taste sensitivities over a day, with limited variation in sweet taste sensitivity being linked to insulin resistance. There were mixed observations of temporal variation in sensitivity to sour and umami tastes, and there were no patterns in sensitivity to bitter taste. Menstrual patterns in sweet taste sensitivity were consistent with patterns in food intake. Other taste modality investigations had mixed findings that had little agreement across studies. Hormonal changes in females influence taste sensitivity to some degree, although the overall patterns are unclear. Seasonal patterns have been less well studied, but there is weak evidence that sweet, salty, and bitter taste sensitivities change across seasons. Differences in seasonal taste patterns have been observed in subgroups susceptible to mental health disorders, requiring further investigation. Patterns of taste sensitivity are evident across multiple temporal dimensions, and more research is needed to determine the influence of these patterns on food intake. Dysregulation of these patterns may also be a marker of certain diseases or health conditions, warranting further investigation. Notably, the alimentary tastes (umami, fat, and carbohydrate) are underrepresented in this research area and require additional investigation.
Marital sorting, family output, and wealth inequality
Authors: Gahramanov Emin , Tang Xueli , Yang Zhenhai , Zhu Shenghao
Published: August 2023

In this article, we analytically model marital sorting, intergenerational transfers, and inequality in a household optimization model with uncertainty. We modify and apply a ‘sorting, reverse sorting’ numerical approach by Demirtas in the context of marriage market mating, illustrating the robustness of our analytical results. We show that the parameters of the family production function play an important role in driving the path of an economy’s inequality. One finding is that, under assortative mating, factor shares in the family production function positively affect inequality, while under disassortative mating, the relationship between the factor shares and inequality is U-shaped. This and other results that we obtain can stimulate further empirical research, holding potentially important policy implications.
Delayed and Attenuated Antibody Responses to Coronavirus Disease 2019 Vaccination With Poor Cross-Variant Neutralization in Solid-Organ Transplant Recipients—A Prospective Longitudinal Study
Authors: Liew May Y , Mathews Josh I , Li Amy , Singh Rohan , Jaramillo Salvador A , Weiss Zoe F , Bowman Kathryn , Ankomah Pierre O , Ghantous Fadi , Lewis Gregory D , Neuringer Isabel , Bitar Natasha , Lipiner Taryn , Dighe Anand S , Kotton Camille N , Seaman Michael S , Lemieux Jacob E , Goldberg Marcia B
Published: August 2023

Background

Therapeutically immunosuppressed transplant recipients exhibit attenuated responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. To elucidate the kinetics and variant cross-protection of vaccine-induced antibodies in this population, we conducted a prospective longitudinal study in heart and lung transplant recipients receiving the SARS-CoV-2 messenger RNA (mRNA) 3-dose vaccination series.

Methods

We measured longitudinal serum antibody and neutralization responses against the ancestral and major variants of SARS-CoV-2 in SARS-CoV-2-uninfected lung (n = 18) and heart (n = 17) transplant recipients, non–lung-transplanted patients with cystic fibrosis (n = 7), and healthy controls (n = 12) before, during, and after the primary mRNA vaccination series.

Results

Among healthy controls, strong anti-spike responses arose immediately following vaccination and displayed cross-neutralization against all variants. In contrast, among transplant recipients, after the first 2 vaccine doses, increases in antibody concentrations occurred gradually, and cross-neutralization was completely absent against the Omicron B.1.1.529 variant. However, most (73%) of the transplant recipients had a significant response to the third vaccine dose, reaching levels comparable to those of healthy controls, with improved but attenuated neutralization of immune evasive variants, particularly Beta, Gamma, and Omicron. Responses in non–lung-transplanted patients with cystic fibrosis paralleled those in healthy controls.

Conclusions

In this prospective, longitudinal analysis of variant-specific antibody responses, lung and heart transplant recipients display delayed and defective responses to the first 2 SARS-CoV-2 vaccine doses but significantly augmented responses to a third dose. Gaps in antibody-mediated immunity among transplant recipients are compounded by decreased neutralization against Omicron variants, leaving many patients with substantially weakened immunity against currently circulating variants.
Using the Standing and Walking Assessment Tool at Discharge Predicts Community Outdoor Walking Capacity in Persons With Traumatic Spinal Cord Injury
Authors: Hong Heather A , Walden Kristen , Laskin James J , Wang Di , Kurban Dilnur , Cheng Christiana L , Guilbault Lindsey , Dagley Erica , Wong Chelsea , McCullum Shane , Gagnon Dany H , Lemay Jean-François , Noonan Vanessa K , Musselman Kristin E ,   The Canadian SCI Standing and Walking Measures Group
Published: August 2023

Objective

The Standing and Walking Assessment Tool (SWAT) standardizes the timing and content of walking assessments during inpatient rehabilitation by combining 12 stages ranging from lowest to highest function (0, 0.5, 1A, 1B, 1C, 2A, 2B, 2C, 3A, 3B, 3C, and 4) with 5 standard measures: the Berg Balance Scale, the modified Timed “Up & Go” test, the Activities-specific Balance Confidence Scale, the modified 6-Minute Walk Test, and the 10-Meter Walk Test (10MWT). This study aimed to determine if the SWAT at rehabilitation discharge could predict outdoor walking capacity 1-year after discharge in people with traumatic spinal cord injury.

Methods

This retrospective study used data obtained from the Rick Hansen Spinal Cord Injury Registry from 2014 to 2020. Community outdoor walking capacity was measured using the Spinal Cord Independence Measure III (SCIM III) outdoor mobility score obtained 12 (±4) months after discharge. Of 206 study participants, 90 were community nonwalkers (ie, SCIM III score 0–3), 41 were community walkers with aids (ie, SCIM III score 4–6), and 75 were independent community walkers (ie, SCIM III score 7–8). Bivariate, multivariable regression, and an area under the receiver operating characteristic curve analyses were performed.

Results

At rehabilitation discharge, 3 significant SWAT associations were confirmed: 0–3A with community nonwalkers, 3B/higher with community walkers with and without an aid, and 4 with independent community walkers. Moreover, at discharge, a higher (Berg Balance Scale, Activities-specific Balance Confidence Scale), faster (modified Timed “Up & Go,” 10MWT), or further (10MWT) SWAT measure was significantly associated with independent community walking. Multivariable analysis indicated that all SWAT measures, except the 10MWT were significant predictors of independent community walking. Furthermore, the Activities-Specific Balance Confidence Scale had the highest area under the receiver operating characteristic score (0.91), demonstrating an excellent ability to distinguish community walkers with aids from independent community walkers.

Conclusion

The SWAT stage and measures at discharge can predict community outdoor walking capacity in persons with traumatic spinal cord injury. Notably, a patient’s confidence in performing activities plays an important part in achieving walking ability in the community.

Impact

The discharge SWAT is useful to optimize discharge planning.
The prime number theorem for primes in arithmetic progressions at large values
Authors: Lee Ethan Simpson
Published: August 2023

Assuming the Riemann hypothesis, we prove the latest explicit version of the prime number theorem for short intervals. Using this result, and assuming the generalised Riemann hypothesis for Dirichlet L-functions is true, we then establish explicit formulae for $\psi(x,\chi)$, $\theta(x,\chi)$ and an explicit version of the prime number theorem for primes in arithmetic progressions that hold for general moduli $q\geq 3$. Finally, we restrict our attention to $q\leq 10\,000$ and use an exact computation to refine these results.
E36 Juvenile scleroderma in rheumatology unit Tripoli children hospital
Authors: Hashad Soad S , Etayari Hala M , Almsellati Iman A , Etfil Majda N , Altwati Aya , Awhida Zuhaira
Published: August 2023

Introduction

Juvenile scleroderma is a rare chronic systemic connective tissue disease. It is classified into two main forms: localized scleroderma and systemic sclerosis. Since it is rare in children, many aspects of the disease remain undiscussed.

Aim

To study the clinical and demographic characteristics of patients diagnosed with various types of scleroderma who presented at the pediatric rheumatology unit in Tripoli Children hospital from the year 2000–2022

Materials and methods

This is a retrospective case series conducted by reviewing the files of patients with scleroderma diagnosed and followed up in pediatric rheumatology unit from year 2000–2022 and collecting the data regarding patients’ demographics, time of diagnosis, clinical features, and laboratory results.

Results

Seven patients who met preliminary classification criteria for JSS were included. 2 males and 5 females. 1 patient with systemic sclerosis, 1 patient with linear morphea, 2 patients with generalized morphea, 1 patient with Parry Romberg syndrome, 1 patient with CREST syndrome, and 1 patient with deep morphea. The mean age at diagnosis was 8.2 ± 4.5 years. The first symptom attributable to JSS was hyperpigmented skin patches in 5 cases, no one presented with Raynaud's phenomenon. Respiratory involvement occurred in one patient, and it manifested as dyspnea as well as abnormal imaging and/or pulmonary function tests showed mild restrictive lung disease. Dysphagia was the commonest gastrointestinal symptom (4 patients, 57%). The most frequent musculoskeletal symptom was arthritis found in in 4 (57.1%) patients. Uveitis in 1 (14.3%), ANA was positive in 4 (57%) children: RF positive in 2 (28.6%) patients, ENA negative in the 7 (100%) patients. Skin biopsy was done in 2 patients and was consistent with scleroderma. Regarding treatment, six patients received MTX, one patient received prednisolone and one patient received MMF.

Conclusion

This report is the first describing Libyan patients with scleroderma. As reported in the literature, localized forms are more common than systemic sclerosis. Also a rare form of scleroderma (Parry Romberg syndrome) was present. Data about the disease mainly based on studies on adults and we need more studies on pediatric patients.

Ethics

Our study was approved by local ethical committee of pediatric department at Tripoli children hospital.
Comparison between endocrine activity assessed using ToxCast/Tox21 database and human plasma concentration of sunscreen active ingredients/UV filters
Authors: Onyango David O , Selman Bastian G , Rose Jane L , Ellison Corie A , Nash J F
Published: August 2023

Sunscreen products are composed of ultraviolet (UV) filters and formulated to reduce exposure to sunlight thereby lessening skin damage. Concerns have been raised regarding the toxicity and potential endocrine disrupting (ED) effects of UV filters. The ToxCast/Tox21 program, that is, CompTox, is a high-throughput in vitro screening database of chemicals that identify adverse outcome pathways, key events, and ED potential of chemicals. Using the ToxCast/Tox21 database, octisalate, homosalate, octocrylene, oxybenzone, octinoxate, and avobenzone, 6 commonly used organic UV filters, were found to have been evaluated. These UV filters showed low potency in these bioassays with most activity detected above the range of the cytotoxic burst. The pathways that were most affected were the cell cycle and the nuclear receptor pathways. Most activity was observed in liver and kidney-based bioassays. These organic filters and their metabolites showed relatively weak ED activity when tested in bioassays measuring estrogen receptor (ER), androgen receptor (AR), thyroid receptor, and steroidogenesis activity. Except for oxybenzone, all activity in the endocrine assays occurred at concentrations greater than the cytotoxic burst. Moreover, except for oxybenzone, plasma concentrations (Cmax) measured in humans were at least 100× lower than bioactive (AC50/ACC) concentrations that produced a response in ToxCast/Tox21 assays. These data are consistent with in vivo animal/human studies showing weak or negligible endocrine activity. In sum, when considered as part of a weight-of-evidence assessment and compared with measured plasma concentrations, the results show these organic UV filters have low intrinsic biological activity and risk of toxicity including endocrine disruption in humans.
Self-reported Xylazine Experiences: A Mixed-methods Study of Reddit Subscribers
Authors: Spadaro Anthony , O'Connor Karen , Lakamana Sahithi , Sarker Abeed , Wightman Rachel , Love Jennifer S. , Perrone Jeanmarie
Published: August 2023

Objectives

Xylazine is an α2-agonist increasingly prevalent in the illicit drug supply. Our objectives were to curate information about xylazine through social media from people who use drugs (PWUDs). Specifically, we sought to answer the following: (1) What are the demographics of Reddit subscribers reporting exposure to xylazine? (2) Is xylazine a desired additive? And (3) what adverse effects of xylazine are PWUDs experiencing?

Methods

Natural language processing (NLP) was used to identify mentions of “xylazine” from posts by Reddit subscribers who also posted on drug-related subreddits. Posts were qualitatively evaluated for xylazine-related themes. A survey was developed to gather additional information about the Reddit subscribers. This survey was posted on subreddits that were identified by NLP to contain xylazine-related discussions from March 2022 to October 2022.

Results

Seventy-six posts were extracted via NLP from 765,616 posts by 16,131 Reddit subscribers (January 2018 to August 2021). People on Reddit described xylazine as an unwanted adulterant in their opioid supply. Sixty-one participants completed the survey. Of those who disclosed their location, 25 of 50 participants (50%) reported locations in the Northeastern United States. The most common route of xylazine use was intranasal use (57%). Thirty-one of 59 (53%) reported experiencing xylazine withdrawal. Frequent adverse events reported were prolonged sedation (81%) and increased skin wounds (43%).

Conclusions

Among respondents on these Reddit forums, xylazine seems to be an unwanted adulterant. People who use drugs may be experiencing adverse effects such as prolonged sedation and xylazine withdrawal. This seemed to be more common in the Northeast.
Diagnosis and Management of an Intramyometrial Ectopic Pregnancy Within a Septate Uterus
Authors: Gilmore Emma , Gutman Sarah , Kim Hyun Tae , Roe Andrea Hsu
Published: August 2023

BACKGROUND:

An intramyometrial pregnancy is a rare form of ectopic pregnancy, making up an estimated 1% of all ectopic pregnancies. Previously described management options have included surgical excision in the emergency setting.

CASE:

A 32-year-old woman, gravida 4 para 0, at 6 0/7 weeks of gestation by last menstrual period, was noted to have a gestational sac implanted entirely within the uterine myometrium. Ultrasonography and magnetic resonance imaging confirmed the presence of an intramyometrial ectopic pregnancy within a septate uterus. The patient's abnormal pregnancy was successfully treated with multidose methotrexate.

CONCLUSION:

Intramyometrial pregnancy is a rare entity that should be considered when it is suggested by ultrasonography or if an intrauterine pregnancy is surgically inaccessible from the endometrial cavity. In a stable patient, multidose systemic methotrexate may be a feasible management strategy.
Reproductive Carrier Screening Results With Maternal Health Implications During Pregnancy
Authors: Souter Vivienne , Prigmore Brittany , Becraft Emily , Repass Elizabeth , Smart Trevor , Sanapareddy Nina , Schweitzer Melissa , Ortiz J. Bryce , Wang Yang , Benn Peter
Published: August 2023

OBJECTIVE:

To identify conditions on a reproductive carrier screening panel with the potential for carrier manifestations during pregnancy and review the implications for obstetric care.

METHODS:

This was a retrospective cross-sectional study of consecutive samples from female patients aged 18–55 years submitted to a commercial laboratory for a 274-gene carrier screening panel (January 2020 to September 2022). A literature review was performed to identify genes on the panel with potential for pregnancy complications in carriers. Carrier expression and published recommendations for clinical management were reviewed.

RESULTS:

We identified 12 genes with potential for carrier manifestations during pregnancy based on reports in the literature: nine with manifestations irrespective of the fetal genetic status (ABCB11, COL4A3, COL4A4, COL4A5, DMD, F9, F11, GLA, and OTC) and three (CPT1A, CYP19A1, and HADHA) with manifestations only if the fetus is affected by the condition. Manifestations included cardiomyopathy, hemorrhage, gestational hypertensive disorders, cholestasis of pregnancy, acute fatty liver, hyperammonemic crisis, and maternal virilization. Published recommendations for carrier management were identified for 11 of the 12 genes. Of 91,637 tests performed during the study period, a pathogenic or likely pathogenic variant was identified in 2,139 (2.3%), giving a carrier frequency for any of the 12 genes of 1 in 43 (95% CI 1/41–45) 1,826 (2.0%) of the study population were identified as carriers for one of the nine genes with the potential for carrier manifestations irrespective of an affected or unaffected fetus.

CONCLUSION:

Approximately 1 in 40 female patients were identified as carriers for a condition with potential for maternal manifestations in pregnancy, including some serious or even life-threatening complications. Obstetric care professionals should be aware of the possibility of pregnancy complications among carriers and the available recommendations for management.

FUNDING SOURCE:

This study was funded by Natera, Inc.
Do Long-Segment Blocking Screws Increase the Stability of Intramedullary Nail Fixation in Proximal Tibia Fractures, eliminating the “Bell-clapper Effect?”
Authors: Stenquist Derek S , McCaskey Meghan , Diaz Miguel , Munassi Steven D , Ayala Giovanni , Donohue David , Mir Hassan R
Published: August 2023

Objectives:

To determine change in stiffness and horizontal translation of a geriatric extra-articular proximal tibia fracture model after intramedullary nailing with distal (long) segment blocking screws versus proximal (short) segment blocking screws.

Methods:

Unstable extra-articular proximal tibia fractures (OTA/AO 41-A3) were created in twelve geriatric tibias. Intramedullary nails were locked with a standard construct (4 proximal screws and 2 distal screws). Specimens were then divided into 2 groups (6 matched pairs per group). Group 1 had a blocking screw placed lateral to the nail in the proximal segment (short-segment). Group 2 had a blocking screw placed 1cm distal to the fracture and medial to the nail (long segment). Specimens were then axially loaded and cycled to failure or cycle completion (50,000 cycles).

Results:

Long segment blocking screws significantly decreased the amount of horizontal translation at the fracture site compared to short segment screws (0.77 mm vs. 2.0 mm (p=.039). They also resulted in greater baseline stiffness, although this difference was not significant (807.32± 216.95N/mm vs 583.12 ± 130.1 N/mm, p=.072). There was no difference in stiffness after cyclic loading or survival through 50,000 cycles between the long- and short-segment groups.

Conclusion:

Long-segment blocking screws added to an intramedullary nail construct resulted in decreased horizontal translation at the fracture site compared to short-segment screws in this model of a geriatric proximal tibia fracture.

Clinical Relevance:

Blocking screws are commonly used to aid in fracture alignment during intramedullary nailing of proximal tibia fractures. Even when not required to attain or maintain alignment, the addition of a blocking screw in the distal (long) segment may help mitigate the “Bell-clapper Effect” in geriatric patients.
Early Treatment of Acetabular Fractures via an Anterior Approach Increases Blood Loss but not Packed Red Blood Cell Transfusion
Authors: Mullis Brian H. , Chang Joshua HS , Shah Nihar , Sabbagh Ramsey S. , Yu Qing , Archdeacon Michael T. , Sagi H Claude , Natoli Roman M.
Published: August 2023

Objective:

To determine if time from hospital admission to surgery for acetabular fractures using an anterior intrapelvic (AIP) approach affected blood loss.

Design:

Multicenter retrospective study.

Setting:

Three level 1 trauma centers at 2 academic institutions.

Patients:

195 adult (age >18) patients with adequate records to complete analysis and no pre-existing coagulopathy.

Intervention:

AIP approach without other significant same day procedures (irrigation and debridement and external fixation were the only other allowed procedures).

Outcome Measurements:

Multiple methods for evaluating blood loss were investigated, including estimated blood loss (EBL), calculated blood loss (CBL), and packed red blood cell (PRBC) transfusion requirement.

Results:

On continuous linear analysis, increasing time from admission to surgery was significantly associated with decreasing CBL at 24 hours (-1.45 mL per hour by Gross, p=0.003; -0.440 g of Hgb per hour by Hgb balance, p=0.003) and 3 days (-1.69 mL per hour by Gross, p=0.013; -0.497 g of Hgb per hour by Hgb balance, p=0.010) postoperative, but not EBL or PRBC transfusion. Using 48-hours from admission to surgery to define early versus delayed, blood loss was significantly greater in the early group compared to delayed [453 (IQR 277-733) mL early versus 364 (IQR 160-661) delayed by Gross, p=0.017; 165 (IQR 99-249) g early versus 143 (IQR 55-238) g delayed by Hgb balance, p=0.035], but not EBL or PRBC transfusion. Additionally, in multivariate linear regression, neither giving tranexamic acid nor administering prophylactic anticoagulation for venous thromboembolism on the morning of surgery affected blood loss at 24 hours or 3 days postoperative.

Conclusion:

There is higher blood loss with early surgery using an AIP approach, but early surgery did not affect PRBC transfusion and may not be clinically relevant.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
99mTc-HFAPi imaging identifies early myocardial fibrosis in the hypertensive heart
Authors: Xie Boqia , Li Lina , Lin Mingming , Nanna Michele , Su Yao , Hua Cuncun , Leng Chenlei , Gan Qianqian , Xi Xiao-Ying , Wang Yidan , Yao Dandan , Wang Li , Yu Liping , Zhao Lei , Zhang Ye-ping , Dou Kefei , Su Pixiong , Lv Xiuzhang , Jia Bing , Yang Min-Fu
Published: August 2023

Background:

This study aimed to explore whether 99mTc-radiolabeled fibroblast activation protein inhibitor (99mTc-HFAPi) imaging can detect early myocardial fibrosis in the hypertensive heart.

Methods:

In the experimental model, spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto rats (WKYs) were randomly divided into three groups (8, 16, and 28 weeks). The animals underwent 99mTc-HFAPi imaging and echocardiography. Autoradiography and histological analyses were performed in the left ventricle. The mRNA and protein expression level of the fibroblast activation protein (FAP) and collagen I were measured using quantitative PCR and western blot. In the clinical investigation, a total of 106 patients with essential hypertension and 20 gender-matched healthy controls underwent 99mTc-HFAPi imaging and echocardiography.

Results:

In-vivo and in-vitro autographic images demonstrated diffusely enhanced 99mTc-HFAPi uptake in the SHR heart starting at week 8, before irreversible collagen deposition. The mRNA and protein levels of FAP in SHRs began to increase from week 8, whereas changes in collagen I levels were not detected until week 28. In the clinical investigation, even in hypertensive patients with normal diastolic indicators, normal left ventricular geometry, and normal global longitudinal strain (GLS), the prevalence of increased 99mTc-HFAPi uptake reached 34, 41, and 20%, respectively, indicating that early fibrogenesis precedes structural and functional myocardial abnormalities.

Conclusion:

In hypertension, 99mTc-HFAPi imaging can detect early fibrotic process before myocardial functional and structural changes.
Comparative effectiveness of pain control between opioids and gabapentinoids in older patients with chronic pain
Authors: Kim Emily , Raji Mukaila A. , Westra Jordan , Wilkes Denise , Kuo Yong-Fang
Published: August 2023

Gabapentinoid (GABA) prescribing has substantially increased while opioid prescribing has decreased since the 2016 Centers for Disease Control and Prevention Guidelines restricted opioid prescribing for chronic pain. The shift to GABA assumes equal analgesic effectiveness to opioids, but no comparative analgesic effectiveness data exist to support this assumption. We compared GABA to opioids by assessing changes in pain interfering with activities (activity-limiting pain) over time in patients with chronic pain. We used 2017 to 2019 data from a 20% national sample of Medicare beneficiaries diagnosed with chronic pain who initiated a GABA or opioid prescription for ≥30 continuous days and received home health care in the study year. The main outcome was the difference in reduction in pain score from pre- to post-prescription assessments between the 2 groups. Within a 60-day window before-and-after drug initiation, our sample comprised 3208 GABA users and 2846 opioid users. Reduction in post-prescription scores of pain-related interference with activities to less-than-daily pain was 48.1% in the GABA group and 41.7% in the opioid group; this remained significant (odds ratio = 1.29, 95% confidence interval: 1.17-1.43, P < 0.0001) after adjustment for patient demographics and comorbidities. The adjusted difference in reduced pain-related interference score between the 2 groups was −0.10 points on a 0 to 4 scale (P = 0.01). Gabapentinoid use had greater odds of less-than-daily pain post-prescription, in a dose-dependent manner. Thus, GABA use was associated with a larger reduction in chronic pain than opioids, with a larger effect at higher GABA dosage. Future research is needed on functional outcomes in patients with chronic pain prescribed GABA or opioids.
The impact of end-stage kidney disease on mortality in patients after acute myocardial infarction: A nationwide study
Authors: Chiang Cheng-Hung , Hung Wan-Ting , Tai Ta-Hsin , Cheng Chin-Chang , Lin Kun-Chang , Kuo Shu-Hung , Lin Su-Chiang , Tang Pei-Ling , Gao Chong-En , Weng Pei-Yu , Ko Yu-Ling , Fu Yun-Ju , Kuo Feng-Yu , Huang Wei-Chun
Published: August 2023

Background:

This study aimed to evaluate the impact of end-stage kidney disease (ESKD) on mortality in patients with first-time acute myocardial infarction (AMI).

Methods:

This was a retrospective nationwide cohort study. Patients diagnosed with first-time AMI between January 1, 2000, and December 31, 2012, were included. All patients were followed-up until death or December 31, 2012, whichever occurred first. A one-to-one propensity score matching technique was used to match patients with ESKD to those without ESKD of similar sex, age, comorbidities, and coronary intervention (including percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]). Kaplan-Meier cumulative survival curves were constructed to compare AMI patients with and without ESKD.

Results:

A total of 186 112 patients were enrolled and 8056 patients with ESKD were identified. Propensity score matched 8056 patients without ESKD were included in the comparison. Overall, the 12-year mortality rate was significantly higher in patients with ESKD than in those without ESKD (log-rank p < 0.0001), including the sex, age, and PCI and CABG subgroups. In Cox proportional-hazard regression analysis, ESKD was an independent risk factor for mortality after patients suffered from first-time AMI (hazard ratio, 1.77; 95% CI, 1.70-1.84; p < 0.0001). A forest plot for subgroup analysis revealed that in AMI patients, ESKD had a higher impact on mortality in male; younger age; without comorbidities such as hypertension, diabetes mellitus, peripheral vascular disease, heart failure, cerebrovascular accident, and chronic obstructive pulmonary disease; and receiving PCI and CABG subgroups.

Conclusion:

ESKD significantly increases the mortality risk in patients with first-time AMI, including both sexes, different ages, and whether PCI or CABG was performed. In patients with AMI, ESKD has a high impact on mortality in male, younger age, without comorbidities, and those undergoing PCI and CABG.
Changes in insulin resistance, glucose effectiveness, and first and second phases of insulin secretion in women aged 45–60 years old in Taiwan
Authors: Wang Chen-Yu , Wu Chung-Ze , Chen Fang-Yu , Pei Dee , Huang Li-Ying
Published: August 2023

Background:

In women after menopause, the incidence of diabetes mellitus increases. Increased insulin resistance (IR), decreased glucose effectiveness (GE), and the first and second phases of insulin secretion (FPIS and SPIS), are the four most important factors that trigger glucose intolerance and diabetes (diabetogenic factor [DF]). In the cross-sectional study, we enrolled nondiabetic women between the ages of 45 and 60 years to observe the changes in DFs during the perimenopausal period and to elucidate the underlying mechanisms of diabetes in menopausal women.

Methods:

We randomly enrolled 4194 women who underwent health checkups. Using demographic and biochemical data, IR, FPIS, SPIS, and GE were calculated using previously published equations. The relationship between the DFs and age was evaluated using a simple correlation.

Results:

Body mass index, blood pressure, fasting plasma glucose, low-density lipoprotein cholesterol, triglyceride, and SPIS were higher, and GE was lower in older women (≥52 years old). A significant decrease in GE and increased SPIS were observed with age. However, no changes were observed in IR or FPIS.

Conclusion:

The IR and FPIS did not change during perimenopause. Increased SPIS may compensate for the decrease in GE, which is probably one of the reasons for the higher incidence of diabetes in menopausal women.
Epidemiology of patients presenting to the emergency department with acute febrile illness in the summer months in Karachi, Pakistan: a cross-sectional study
Authors: Khan Nadeem Ullah , Khan Uzma R. , Soomar Salman M. , Ahmed Naveed , Dhalla Zeyanna , Subhani Faysal , Ali Noman , Afzal Khan Badar , Razzak Junaid A.
Published: August 2023

Background:

Low and middle-income countries, including Pakistan, encounter many acute, undifferentiated fevers in their emergency departments (EDs), especially in the summer. There is a need to understand the prevalence and etiologies of fever to create sustainable risk stratification systems and better identification processes for more efficient treatments. This study aims to determine the patterns, causes, and outcomes of patients presenting to the ED with a fever in the summer months in Karachi, Pakistan.

Patients and methods:

This was a cross-sectional surveillance study conducted in the summers of 2017 and 2018 in the EDs of four tertiary care hospitals in Karachi, Pakistan. Patients 18 years of age and older, both males and females, that presented with a fever within 48 h were enrolled in the study. The study sample was 5034. Prior comorbidities, medication history, and treatment offered for the illness and diagnosis were noted. The data were stratified by years, that is, 2017–2018. A χ
2-test and a one-way analysis of variance test were applied to check the association between fever presentation in years and covariates.

Results:

Of the 5034 patients, 3045 (60.5%) presented in 2017 and 1989 (39.5%) presented in 2018. Almost half of the patients who presented with fever to the ED were between 25 and 44 years of age [2383 (47.3%)]. A majority of those presenting were male [3049 (60.6%)]. Most of the patients had a fever recorded between 101 and 102°F [1038 (20.6%)]. The most common accompanying symptoms were headache [2636 (52.4%)] and nausea and vomiting [2274 (45.2%)]. The majority of the patients were diagnosed as viral fever [2390 (47.5%)]. Patients were managed with antibiotics [3342 (66.4%)] and intravenous fluids [2521 (50.1%)] and a majority of patients were discharged [4677 (93.8%)].

Conclusions:

Fever is a common presentation in the ED. Understanding the frequency of the causative agent will help improve diagnosis and the judicious use of antibiotics.
Immunotoxicity induced by occupational inhalation exposure to waste anesthetic gases: a historical cohort study
Authors: Neghab Masoud , Amiri Fatemeh , Zare Mehdi , Zareei Fayegheh
Published: August 2023

Background:

This study was undertaken to ascertain whether long-term occupational exposure to inhalational anesthetic, was associated with any significant alteration in the parameters of immune function.

Materials and methods:

This was a historical cohort study in which 30 male participants with at least one year of work experience in the operating room at the time of the study and 30 unexposed referent subjects were investigated. Exposure levels were quantified by measuring the urinary concentrations of nitrous oxide (N2O), isoflurane, and sevoflurane gases by headspace gas chromatography-mass spectrometry. Serum concentrations of interleukin-4 (IL-4), Th2-type cytokines, and interferon-gamma (IFN-γ) were measured by the ELISA method. Additionally, an automated hematology analyzer was used for the white blood cell count and white blood cell differential test. The data were analyzed using SPSS software for Windows version 21.

Results:

Mean urinary concentrations of N2O, isoflurane, and sevoflurane were found to be 211.57±75.15, 4.06±0.96, and 19.51±12.96  ppb, respectively. In simplistic statistical data analysis, significant differences were noted between exposed and control groups as far as the mean serum cytokines levels (IFN-γ, IL-4) were concerned. Furthermore, after adjusting for important confounders, statistical analysis showed that the IFN-γ, IL-4, and the ratio of IFN-γ/IL-4 were significantly higher in the exposed group than in the referent subjects.

Conclusion:

These findings provide corroborative evidence to further substantiate the contention that exposure to anesthetics agents (N2O, isoflurane, and sevoflurane) is associated with subtle, subclinical, prepathological changes in the parameters of immune function. The long-term ramification of these changes requires further investigation.
Mitro-aortic infective endocarditis on bicuspid aortic valve multicomplicated: a case report
Authors: Boutaybi Mohammed , Doudouh Othmane , Darar Assoweh Charmake , El Abbassi Oussama , Ismaili Nabila , El Ouafi Noha
Published: August 2023

Infective endocarditis (IE) is a rare but serious disease, and despite improvements in diagnostic and therapeutic tools, it remains associated with high mortality. It can develop in a healthy heart, but most commonly in underlying heart disease. The authors discuss a 34-year-old patient, who has presented for 4 months with generalized asthenia, fever, and chills, without any notion of chest pain, arthralgias. On admission, the patient was conscious, hemodynamically, and respiratory stable, the temperature was 38.5°C. The cardiac exam heart revealed a systolic murmur rated 4/6th at the mitral focus. Transthoracic echocardiography showing vegetation on the mitral and aortic valve. Three blood cultures were taken at 1 h intervals, all positive for enterococci, thoracoabdominal and brain computed tomography scan with contrast injection was performed showing, ischemic stroke, aortic coarctation, splenic and renal infarction, mycotic aneurysms in the descending aort. IE can be the cause of several extracardiac manifestations, through vascular and/or immunological phenomena. Embolic complications are the most frequent extracardiac complications and are secondary to septic emboli from the vegetations. The prognosis of IE is worsened by the addition of cardiac and extracardiac complications such as mycotic aneurysms and septic embolic events.
A cross-sectional study of MIS TLIF in treatment of spondylolisthesis: initial good results from 92 Vietnamese patients
Authors: Nguyen Long Hoang , Manh Do Hung , Pham Phong Hong , Bui Hoang Minh , Duong Anh Tung , Nguyen Khanh Manh , Dinh Son Ngoc , Doan Ha Thi-Ngoc , Nguyen Tien Le-Bao
Published: August 2023

Introduction:

Minimally invasive transforaminal lumbar interbody fusion has proven effectiveness in treating spondylolisthesis, but there were few reports applying the technique from scarce resourcing developing countries. In this study, the authors report the results and share our experience of minimally invasive spinal transforaminal lumbar interbody fusion in spondylolisthesis treatment in Vietnamese patients.

Materials and methods:

In this study, the authors enroled 92 patients diagnosed with single-level, grade I or grade II lumbar spondylolisthesis from January 2019 to October 2022.

Results:

The median age in our study was 47.79±12.61 (range 15–75), the male/female ratio was 1/2.3. The mean disease duration was 28.57 months. Conventional X-ray images showed that there were 74 patients (80.43%) with spondylolisthesis grade I, 18 patients (19.57%) with grade II. Spondylolisthesis occured mainly in L4–L5 with 53 patients (57.61%). The isthmic sign was recorded in 16 patients (31.4%). The mean blood loss was 149.46 ml. Patients walked on average of 3.22 days after surgery. VAS score reduced significantly in both back and leg. Spinal function improved significantly with a preoperative Owestry Disability Index of 48.18% decrease to 15.18% 12 months after surgery. The surgical results were good and excellent at 95.00% after 12 months of surgery according to Macnab scale. The fusion rate reached 97.50%.

Conclusions:

The results of this Macnab's classification study show that minimally invasive spinal transforaminal lumbar interbody fusion is an effective treatment for spondylolisthesis with less pain, less blood loss after surgery, and high fusion rate.
The use of simulators to acquire ERCP skills: a systematic review
Authors: Georgiou Konstantinos , Atliev Kiril T. , Oussi Ninos , Boyanov Nikola , Sandblom Gabriel , Enochsson Lars
Published: August 2023

Background and Aims:

Endoscopic retrograde cholangiopancreatography (ERCP) is a technically demanding diagnostic and therapeutic endoscopic procedure with a high risk for adverse events such as post-ERCP pancreatitis and bleeding. Since endoscopists with less experience have higher adverse event rates, the training of new residents on ERCP simulators has been suggested to improve the resident’s technical skills necessary for ERCP. However, there is a lack of consensus on whether the training program should focus on a threshold number of procedures or be more tailored to the individual’s performance. Furthermore, there is also disagreement on which form of simulator(s) should be used. Therefore, the primary outcome of this systematic review was to study the extent to which simulators used for ERCP training are correctly validated.

Methods:

In 2022, a systematic search of the literature was conducted on MEDLINE and SCOPUS under the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 protocol seeking articles with the MeSH terms ‘Endoscopic Retrograde Cholangiopancreatography’ OR ‘ERCP’ in combination with ‘simulation’ OR ‘simulator’.

Results:

The search resulted in 41 references. A total of 19 articles met the inclusion criteria and were included in the qualitative analysis. Only one of the articles fulfilled the criteria of a robust validation study.

Conclusions:

Since only one of the 19 articles met the requirements for a thorough and correct validation, further studies with sufficient numbers of subjects, that evaluate complete preclinical training programs based on validated ERCP simulators are warranted.
The effectiveness of neurofeedback on the management of academic performance in students with academic failure: experimental research
Authors: Mohammadi Yasaman , Bozorgkhou Hamed , Hadavi Seyed Morteza , Shojaei Maryam , Rezaei Khodadadi Fatemeh , Najafi Samane , Karimi Zohreh , Mehdibeygi Sarvestani Maryam
Published: August 2023

Background:

The present study aimed to study the impact of neurofeedback on the academic performance of nursing students with academic failure.

Methods:

This study was an experimental one with a pretest–posttest design with a control group. The statistical population of this research was the nursing students of the Faculty of Nursing, Tehran University of Medical Sciences University of Medical Sciences. The sample of this study consisted of 60 individuals chosen by a simple random sampling method and two experiment groups (N=30) and a control group (N=30) were replaced by accident. Neurofeedback was an advanced Raven test and a researcher-made questionnaire for data collection. Thereafter, the experimental group was treated with neurofeedback for 7–10 weeks and 20 50-min therapeutic sessions as the experimental condition. In the first 130 s, the baseline was determined for the individual, and during the session, the baseline was practiced. Each session consisted of six exercises, each lasting 7 min.

Results:

The results of the covariance analysis showed that students who had an educational drop and were trained in neurofeedback sessions showed a significant increase in the next half (P<0.05) compared to the control group.

Conclusion:

The results of this study showed that neurofeedback is an effective method for managing the academic performance of nursing students with academic failure.