bluuebunny/crossref_metadata_2025 huggingface dataset:
Age Differences in Thermal Pain Responses: A Direct Laboratory Comparison
Authors: Shackleton Delaine A , Castillo Louise I R , Hampton Amy J D , Volodin Andrei , Hadjistavropoulos Thomas
Published: April 2023

Objectives

According to a widely cited assertion, older adults are less likely than younger individuals to express pain complaints. Age-related differences in pain responses have been discussed in the literature despite a paucity of research involving direct comparisons of younger and older adults’ pain reactions (i.e., verbal, nonverbal) in the context of a single experimental investigation. Our goal was to test the hypothesis that older adults are more stoic than younger adults in their expression of pain.

Methods

We measured trait stoicism as well as multiple responses to thermal pain.

Results

In contrast to suggestions in the literature, equivalence testing indicated that older and younger adults displayed similar verbal and nonverbal pain responses. Our results suggest that older adults are no more stoic about their pain than are younger persons.

Discussion

This is the first attempt to explore a wide array of age differences in pain expression within the context of a single experimental study.
Speaking the Same Language: Team Science Approaches in Aging Research for Integrating Basic and Translational Science With Clinical Practice
Authors: Sukoff Rizzo Stacey J , Finkel Toren , Greenspan Susan L , Resnick Neil M , Brach Jennifer S
Published: April 2023

Research on aging is at an important inflection point, where the insights accumulated over the last 2 decades in the basic biology of aging are poised to be translated into new interventions to promote health span and improve longevity. Progress in the basic science of aging is increasingly influencing medical practice, and the application and translation of geroscience require seamless integration of basic, translational, and clinical researchers. This includes the identification of new biomarkers, novel molecular targets as potential therapeutic agents, and translational in vivo studies to assess the potential efficacy of new interventions. To facilitate the required dialog between basic, translational, and clinical investigators, a multidisciplinary approach is essential and requires the collaborative expertise of investigators spanning molecular and cellular biology, neuroscience, physiology, animal models, physiologic and metabolic processes, pharmacology, genetics, and high-throughput drug screening approaches. In an effort to better enable the cross-talk of investigators across the broad spectrum of aging-related research disciplines, a goal of our University of Pittsburgh Claude D. Pepper Older Americans Independence Center has been to reduce the barriers to collaborative interactions by promoting a common language through team science. The culmination of these efforts will ultimately accelerate the ability to conduct first-in-human clinical trials of novel agents to extend health span and life span.
Rigidity of SUn-Type Symmetric Spaces
Authors: Batat Wafaâ , James Hall Stuart , Murphy Thomas , Waldron James
Published: April 2023

We prove that the bi-invariant Einstein metric on $SU_{2n+1}$ is isolated in the moduli space of Einstein metrics, even though it admits infinitesimal deformations. This gives a non-Kähler, non-product example of this phenomenon adding to the famous example of $\mathbb{C}\mathbb{P}^{2n}\times \mathbb{C}\mathbb{P}^{1}$ found by Koiso. We apply our methods to derive similar solitonic rigidity results for the Kähler–Einstein metrics on “odd” Grassmannians. We also make explicit a connection between non-integrable deformations and the dynamical instability of metrics under Ricci flow.
Rebel Governance of Marriage and Sexuality: An Intersectional Approach
Authors: Giri Keshab
Published: April 2023

Extant research links forced marriage and sexual violence in rebel groups with their respective political projects, social control, and group cohesion. However, forced marriage and sexual violence are rare in many rebel groups, including the Maoists in Nepal who claimed to have a “progressive,” “scientific,” and “modern” framework for governing marriage and sexuality. In the light of this puzzle, I ask, what does a noncoercive/nonviolent rebel governance of marriage and sexuality mean for a rebel group's political project of social control and power? What is the gendered impact of such governance? Importantly, how does it impact female combatants at the intersection of multiple oppressions? Using abductive analysis of extensive interviews with female ex-combatants and their leaders, I build a theoretical explanation about the noncoercive/nonviolent governance of marriage and sexuality that is not just linked to the formation, consolidation, and legitimation of political agendas, but also enabled social control and political power for the Maoists. However, this further marginalized those female combatants who were already disadvantaged. I employ a feminist intersectional framework while critically reflecting on my own positionality. The implications of these findings extend beyond Nepal, illuminating dynamics of rebel governance and the complexity of war and postwar social organization.
Whole-genome sequencing confirms a persistent candidaemia clonal outbreak due to multidrug-resistant Candida parapsilosis
Authors: Daneshnia Farnaz , Hilmioğlu-Polat Süleyha , Ilkit Macit , Fuentes Diego , Lombardi Lisa , Binder Ulrike , Scheler Jakob , Hagen Ferry , Mansour Michael K , Butler Geraldine , Lass-Flörl Cornelia , Gabaldon Toni , Arastehfar Amir
Published: April 2023

Objectives

Although perceived as a rare clinical entity, recent studies have noted the emergence of MDR C. parapsilosis (MDR-Cp) isolates from single patients (resistant to both azole and echinocandins). We previously reported a case series of MDR-Cp isolates carrying a novel FKS1R658G mutation. Herein, we identified an echinocandin-naive patient infected with MDR-Cp a few months after the previously described isolates. WGS and CRISPR-Cas9 editing were used to explore the origin of the new MDR-Cp isolates, and to determine if the novel mutation confers echinocandin resistance.

Methods

WGS was applied to assess the clonality of these isolates and CRISPR-Cas9 editing and a Galleria mellonella model were used to examine whether FKS1R658G confers echinocandin resistance.

Results

Fluconazole treatment failed, and the patient was successfully treated with liposomal amphotericin B (LAMB). WGS proved that all historical and novel MDR-Cp strains were clonal and distant from the fluconazole-resistant outbreak cluster in the same hospital. CRISPR-Cas9 editing and G. mellonella virulence assays confirmed that FKS1R658G confers echinocandin resistance in vitro and in vivo. Interestingly, the FKS1R658G mutant showed a very modest fitness cost compared with the parental WT strain, consistent with the persistence of the MDR-Cp cluster in our hospital.

Conclusions

Our study showcases the emergence of MDR-Cp isolates as a novel threat in clinical settings, which undermines the efficacy of the two most widely used antifungal drugs against candidiasis, leaving only LAMB as a last resort. Additionally, surveillance studies and WGS are warranted to effectively establish infection control and antifungal stewardship strategies.
The role of TMS 12 in the staphylococcal multidrug efflux protein QacA
Authors: Dashtbani-Roozbehani Abolfazl , Chitsaz Mohsen , Brown Melissa H
Published: April 2023

Objectives

To elucidate the importance of a region in QacA predicted to be important in antimicrobial substrate recognition.

Methods

A total of 38 amino acid residues within or flanking putative transmembrane helix segment (TMS) 12 of QacA were individually replaced with cysteine using site-directed mutagenesis. The impact of these mutations on protein expression, drug resistance, transport activity and interaction with sulphhydryl-binding compounds was determined.

Results

Accessibility analysis of cysteine-substituted mutants identified the extents of TMS 12, which allowed for refinement of the QacA topology model. Mutation of Gly-361, Gly-379 and Ser-387 in QacA resulted in reduced resistance to at least one bivalent substrate. Interaction with sulphhydryl-binding compounds in efflux and binding assays demonstrated the role of Gly-361 and Ser-387 in the binding and transport pathway of specific substrates. The highly conserved residue Gly-379 was found to be important for the transport of bivalent substrates, commensurate with the role of glycine residues in helical flexibility and interhelical interactions.

Conclusions

TMS 12 and its external flanking loop is required for the structural and functional integrity of QacA and contains amino acids directly involved in the interaction with substrates.
Physiology, Vitalism, and the Contest for Body and Soul in the Antebellum United States
Authors: Riddle Jonathan D
Published: April 2023

In the early nineteenth century, physiology became an increasingly popular and powerful science in the United States. Religious controversy over the nature of human vitality animated much of this interest. On one side of these debates stood Protestant apologists who wedded an immaterialist vitalism to their belief in an immaterial, immortal soul — and therefore to their dreams of a Christian republic. On the other side, religious skeptics argued for a materialist vitalism that excluded anything immaterial from human life, aspiring thereby to eliminate religious interference in the progress of science and society. Both sides hoped that by claiming physiology for their vision of human nature they might direct the future of religion in the US. Ultimately, they failed to realize these ambitions, but their contest posed a dilemma late nineteenth-century physiologists felt compelled to solve: how should they comprehend the relationship between life, body, and soul? Eager to undertake laboratory work and leave metaphysical questions behind, these researchers solved the problem by restricting their work to the body while leaving spiritual matters to preachers. In attempting to escape the vitalism and soul questions, late nineteenth-century Americans thus created a division of labor that shaped the history of medicine and religion for the following century.
Impact of Hospitalizations due to Chronic Health Conditions on Early Child Development
Authors: Fardell Joanna E , Hu Nan , Wakefield Claire E , Marshall Glenn , Bell Jane , Lingam Raghu , Nassar Natasha
Published: April 2023

Objective

To assess the impact of hospitalization for chronic health conditions on early child development and wellbeing at school start.

Methods

We conducted a longitudinal cohort study of children starting school using population-based record linkage of routinely collected admitted hospital data and standardized assessment of early childhood development (Australian Early Developmental Census: AEDC). Developmental vulnerability (DV) was defined as children scoring <10th centile in any one of five developmental domains. Children scoring <10th centile on two or more domains were considered developmentally high-risk (DHR). Children hospitalized with chronic health conditions were compared to children without hospitalizations prior to school start.

Results

Among 152,851 children with an AEDC record, 22,271 (14·6%) were hospitalized with a chronic condition. Children hospitalized with chronic health conditions were more likely to be DHR (adjusted odds ratio 1.25, 95% CI: 1.18–1.31) compared to children without hospitalizations. Children hospitalized more frequently (>7 times) or with longer duration (>2 weeks) had a 40% increased risk of being DHR (1.40, 95% CI: 1.05–1.88 and 1.40, 95% CI: 1.13–1.74, respectively). Children hospitalized with mental health/behavioral/developmental conditions had the highest risk of DHR (2.23, 95% CI: 1.72–2.90). Developmental vulnerability was increased for physical health (1.37, 95% CI: 1.30–1.45), language (1.28, 95% CI: 1.19–1.38), social competence (1.22, 95% CI: 1.16–1.29), communication (1.17, 95% CI: 1.10–1.23), and emotional maturity (1.16, 95% CI: 1.09–1.23).

Conclusions

Frequent and longer duration hospitalizations for chronic health conditions can impact early childhood development. Research and interventions are required to support future development and well-being of children with chronic health conditions who are hospitalized.
Development of optimization method for uniform dose distribution on superficial tumor in an accelerator-based boron neutron capture therapy system
Authors: Sasaki Akinori , Hu Naonori , Matsubayashi Nishiki , Takata Takushi , Sakurai Yoshinori , Suzuki Minoru , Tanaka Hiroki
Published: April 2023

To treat superficial tumors using accelerator-based boron neutron capture therapy (ABBNCT), a technique was investigated, based on which, a single-neutron modulator was placed inside a collimator and was irradiated with thermal neutrons. In large tumors, the dose was reduced at their edges. The objective was to generate a uniform and therapeutic intensity dose distribution. In this study, we developed a method for optimizing the shape of the intensity modulator and irradiation time ratio to generate a uniform dose distribution to treat superficial tumors of various shapes. A computational tool was developed, which performed Monte Carlo simulations using 424 different source combinations. We determined the shape of the intensity modulator with the highest minimum tumor dose. The homogeneity index (HI), which evaluates uniformity, was also derived. To evaluate the efficacy of this method, the dose distribution of a tumor with a diameter of 100 mm and thickness of 10 mm was evaluated. Furthermore, irradiation experiments were conducted using an ABBNCT system. The thermal neutron flux distribution outcomes that have considerable impacts on the tumor’s dose confirmed a good agreement between experiments and calculations. Moreover, the minimum tumor dose and HI improved by 20 and 36%, respectively, compared with the irradiation case wherein a single-neutron modulator was used. The proposed method improves the minimum tumor volume and uniformity. The results demonstrate the method’s efficacy in ABBNCT for the treatment of superficial tumors.
The variational method of moments
Authors: Bennett Andrew , Kallus Nathan
Published: April 2023

The conditional moment problem is a powerful formulation for describing structural causal parameters in terms of observables, a prominent example being instrumental variable regression. We introduce a very general class of estimators called the variational method of moments (VMM), motivated by a variational minimax reformulation of optimally weighted generalized method of moments for finite sets of moments. VMM controls infinitely for many moments characterized by flexible function classes such as neural nets and kernel methods, while provably maintaining statistical efficiency unlike existing related minimax estimators. We also develop inference algorithms and demonstrate the empirical strengths of VMM estimation and inference in experiments.
Avulsion fracture of the calcaneal tuberosity treated with novel surgical technique using the combination of the side-locking loop suture technique and ring pins: a case report
Authors: Shota Morimoto , Tachibana Toshiya , Iseki Tomoya
Published: April 2023

A 78-year-old woman complained of right heel pain when tripping during walking. Radiographs revealed an avulsion fracture of the calcaneal tuberosity. Because the bone fragment was displaced, a novel osteosynthesis using the side-locking loop suture (SLLS) and ring pins was performed. At 3 months after the surgery, non-contrast computed tomography revealed complete bone union. At 2 years postoperatively, she had no symptoms and dysfunctions. Here, we describe a case of avulsion fracture of the calcaneal tuberosity in a 79-year-old female who treated with a novel surgical technique using combination the SLLS technique and ring pins. This surgical technique may be a useful option in the treatment for avulsion fractures of the calcaneal tuberosity.
Semaphorin 3A levels in vascular and nonvascular phenotypes in systemic sclerosis
Authors: Kayaalp Mehmet , Erden Abdulsamet , Apaydin Hakan , Güven Serdar Can , Armağan Berkan , Cağlayan Kayaalp Merve , Andac Uzdogan Esma , Ala Enli Şeymanur , Omma Ahmet , Kucuksahin Orhan
Published: April 2023

Objective

Semaphorin 3A (Sema3A) plays a regulatory role in immune responses. The aim of this study was to evaluate Sema3A levels in patients with systemic sclerosis (SSc), especially in major vascular involvements such as digital ulcer (DU), scleroderma renal crisis (SRC), pulmonary arterial hypertension (PAH), and to compare Sema3A level with SSc disease activity.

Methods

In SSc patients, patients with DU, SRC, or PAH were grouped as major vascular involvements and those without as nonvascular, and Sema3A levels were compared between the groups and with a healthy control group. The Sema3A levels and acute phase reactants in SSc patients, as well as their association with the Valentini disease activity index and modified Rodnan skin score, were evaluated.

Results

The Sema3A values (mean ± SD) were 57.60 ± 19.81 ng/mL in the control group (n = 31), 44.32 ± 5.87 ng/mL in patients with major vascular involvement SSc (n = 21), and 49.96 ± 14.00 ng/mL in the nonvascular SSc group (n = 35). When all SSc patients were examined as a single group, the mean Sema3A value was significantly lower than controls (P = .016). The SSc with major vascular involvement group had significantly lower Sema3A levels than SSc with nonmajor vascular involvement group (P = .04). No correlation was found between Sema3A, acute phase reactants, and disease activity scores. Also, no relationship was observed between Sema3A levels and diffuse (48.36 ± 11.47 ng/mL) or limited (47.43 ± 12.38 ng/mL) SSc types (P = .775).

Conclusion

Our study suggests that Sema3A may play a significant role in the pathogenesis of vasculopathy and can be used as a biomarker in SSc patients with vascular complications such as DU and PAH.
Putative application of Najas marina L. extracts as a source of bioactive compounds and their antioxidant, antimicrobial, antibiofilm, and genotoxic properties
Authors: Radojević Ivana D , Grujović Mirjana Ž , Milošević-Djordjević Olivera , Vukajlović Jovana Tubić , Marković Aleksandra , Grujičić Darko , Ćirić Andrija , Djelić Gorica , Topuzović Marina , Čomić Ljiljana R
Published: April 2023

In this research paper, the total phenols (TP), flavonoids (TF), and tannins (TT) content in the acetone and ethyl acetate extracts of Najas marina L. and the identification and quantification of phenolic acids and flavonoids from the ethyl acetate extract were performed. Antioxidant, antimicrobial, and antibiofilm properties of the mentioned extracts were investigated in vitro. The genotoxic potential was analyzed in cultured human peripheral blood lymphocytes (PBL). The TP and TF content was higher in the ethyl acetate extract, dominated by quercetin (172.4 µg mg−1) and ferulic acid (22.74 µg mg−1), while the TT content was slightly higher in the acetone extract. Both extracts tested showed limited antioxidant effects compared to ascorbic acid. The strongest antibacterial activity was observed with Gram-positive bacteria, particularly Staphylococcus aureus (MIC and MMC at 0.31 mg ml−1) and S. aureus ATCC 25923 (MIC at <0.02 mg ml−1), while antifungal activity was limited. Both extracts tested showed better activity on preformed biofilms. Acetone extract had no genotoxic activity but showed significant genoprotective activity against mitomycin C-induced DNA damage in cultured PBLs. Results of our research demonstrate the potential for the development of plant-based antibacterial and biofilm agents.
Coping With Crises
Authors: Evans Dwight L. , Benton Tami D. , Ellison Katherine
Published: April 2023

This chapter covers the scariest and hardest experiences when caring for someone with a serious mental illness. It explains how loving children will help to get through the experience even if kids who are struggling with bipolar disorder go further in becoming extraordinarily defiant, hostile, and aggressive. Parents need to have regular discussions with their children in an effort to be aware of and address what is going on in their respective lives. Moreover, the chapter discusses how to cope with manic episodes, psychosis, and self-harm. It suggests handling violence at home or calling the police on a child’s out-of-control behavior.
Conclusion
Authors: Evans Dwight L. , Benton Tami D. , Ellison Katherine
Published: April 2023

This chapter reviews the lives of the children affected by bipolar disorder and how it changed for the better. It acknowledges how sheer luck and a parent’s love can make a difference in a child’s life path. Kids with all kinds of mental illness being identified and treated earlier bring hope that they can be helped out of their harmful ruts. Moreover, the pandemic sparked unquestionable damage to the mental health of US children. The chapter tackles progress with policies in improving mental health support. It suggests focusing better on the bigger picture and thinking harder about broader, structural issues that have huge and inequitable impacts on mental health.
Reducing Dyspnea by Optimizing Treatment of Chronic Obstructive Pulmonary Disease
Authors: Wilhelm Miranda , Arnoldi Jennifer
Published: April 2023

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation that is not fully reversible and is associated with an inflammatory response to harmful inhaled particles. Medication therapy is available to provide symptomatic control and, in some cases, to decrease the risk of exacerbations. Inhaled pharmacotherapy is the preferred drug delivery route of administration. If they are used appropriately, four inhalation devices (metered-dose inhalers, dry powder inhalers, soft mist inhalers and nebulizers) have similar efficacy in patients with COPD. This chapter discusses the advantages and disadvantages of the various inhalation drug delivery devices so that providers can individualize pharmacotherapy.
Treating Dyspnea Through Reducing Malignant Pleural Effusion
Authors: Crader Christine A.
Published: April 2023

Malignant pleural effusion can be a common finding with certain types of cancer, especially lung in men with breast and gynecologic in women. Dyspnea develops as the pleural effusion expands, A pleural effusion causes the sensation of dyspnea due to a flattening or even inversion of the diaphragm on the side of the effusion. This leads to a restrictive defect in ventilation, which leads to a decrease in the lung volume and an increase in the work of breathing. This chapter discuss the presentation, diagnosis, prognosis, treatment, and symptom management related to patients with malignant pleural effusion. Treatment and interventions can include thoracentesis, pleurodesis, and placement of a tunneled pleural catheter.
Hip Fracture and Regional Anesthesia
Authors: Ochroch Jason B. , Neuman Mark D.
Published: April 2023

Hip fractures are a very common injury in the elderly population and carry significant risks of morbidity and mortality. There are a variety of factors that increase someone’s risk of sustaining a hip fracture, so identification of these factors and preoperative prevention is of utmost importance. Expedited surgical repair is the standard of care, although significant questions remain regarding the use of general versus neuraxial anesthesia. Multimodal analgesia, including the use of peripheral nerve blockade, is strongly recommended in both the pre- and postoperative environment. Multiple nerve blocks have been developed to block the complex innervation of the hip joint, including the femoral nerve block and fascia iliaca compartment block.
Epidural Placement and Anticoagulation
Authors: Nilforoshan Maryam , Graff Veena , Grosh Taras
Published: April 2023

Rib fractures can result in severe pain that limits respiration and can result in pulmonary complications. Epidural analgesia is the gold standard for treating this pain and avoiding these complications. Epidural analgesia still has extensive applications in controlling different types of pain. Meanwhile, it is not without complications; the development of an epidural hematoma with resultant spinal cord ischemia is one of the serious complications of this technique. Although injury to spinal vasculature during neuraxial analgesia/anesthesia occurs in 3%–12% of cases, the incidence of epidural hematoma is less than 1 in 150,000. This risk is increased by the use of systemic anticoagulants. Encountering patients on anticoagulants who can benefit from neuroaxial analgesia/anesthesia has become everyday practice. The use of anticoagulants is not a contraindication in most the cases. The American Society of Regional Anesthesia (ASRA) has developed guidelines to deal with this problem. These guidelines were updated four times since they were first developed two decades ago. They are based on the medication pharmacokinetics and pharmacodynamics, as well as published reports of developing an epidural hematoma in patients receiving these medications. This chapter reviews these guidelines and alternatives to placing epidural analgesia in case it is contraindicated.
Elective Abdominal Aortic Aneurysm With Epidural Analgesia
Authors: Akerman Michael , Anderson Ariel , Norman Ryan
Published: April 2023

Heparin induced thrombocytopenia (HIT) is an immune-mediated, low blood platelet count as a result of heparin administration. The clinical features, including the recovery of platelet count with discontinuation of heparin therapy and recurrent thrombocytopenia with repeat heparin challenge. After reviewing this chapter, the reader will learn about the different types of heparin induced thrombocytopenia (HIT), how to diagnose and manage HIT, how to manage an epidural catheter in patients who develop HIT and are being treated for it. This chapter also reviews some of the medications used as alternative anticoagulation therapy in HIT. In addition, the chapter reviews common practices of how to evaluate patients for candidacy of neuraxial anesthesia and important considerations and management concerns. Finally, this chapter discusses von Willebrand disease and considerations for neuraxial anesthesia with inherited bleeding disorders.
Barriers and Facilitators to Dialectical Behavior Therapy Skills Groups in the Veterans Health Administration
Authors: Decker Suzanne E , Matthieu Monica M , Smith Brandy N , Landes Sara J
Published: April 2023

Introduction

Dialectical behavior therapy (DBT) is a multimodal evidence-based suicide prevention psychotherapy with barriers to full implementation. This study qualitatively examined barriers and facilitators to the DBT skills group treatment mode, which can be implemented as a stand-alone intervention. Using data from a national mixed-methods program evaluation of DBT in the Veterans Health Administration (VHA), this is the first article to examine barriers and facilitators to DBT skills groups implemented with a DBT consultation team or as a stand-alone intervention.

Materials and Methods

A subset of data from semi-structured telephone interviews of six clinicians and three administrators (n = 9 respondents) was analyzed to provide complementarity and expansion on prior quantitative findings. The data were coded using an iterative process based on content analysis and a codebook based on the Promoting Action on Research Implementation in Health Services framework. The study was approved by the institutional review board for the Palo Alto VA Health Care System.

Results

Barriers and facilitators were organized by Promoting Action on Research Implementation in Health Services domains of evidence, context, and facilitation. Results showed how reduced leadership support and low receptivity to providing DBT skills groups functioned as barriers and also identified a barrier not described earlier in the literature: the perception that this group could conflict with expanding access to care for more veterans. The results showed how leadership supported implementation, including by mapping clinic grids and supporting training, and also revealed how a supportive culture among providers facilitated division of labor between skills group providers, and how offering a treatment that filled a gap in services supported the group. At some sites, a provider with prior DBT experience was instrumental in starting DBT skills groups or developing ongoing training.

Conclusions

Qualitatively analyzed barriers and facilitators to a group-delivered suicide prevention intervention, DBT skills groups, expanded on quantitative findings on the importance of leadership support, culture, and training as facilitators. Future work implementing DBT skills group as a stand-alone treatment will need to address the barrier of receptivity and perceived barriers about access to care.
Dynamics of release factor recycling during translation termination in bacteria
Authors: Prabhakar Arjun , Pavlov Michael Y , Zhang Jingji , Indrisiunaite Gabriele , Wang Jinfan , Lawson Michael R , Ehrenberg Måns , Puglisi Joseph D
Published: April 2023

In bacteria, release of newly synthesized proteins from ribosomes during translation termination is catalyzed by class-I release factors (RFs) RF1 or RF2, reading UAA and UAG or UAA and UGA codons, respectively. Class-I RFs are recycled from the post-termination ribosome by a class-II RF, the GTPase RF3, which accelerates ribosome intersubunit rotation and class-I RF dissociation. How conformational states of the ribosome are coupled to the binding and dissociation of the RFs remains unclear and the importance of ribosome-catalyzed guanine nucleotide exchange on RF3 for RF3 recycling in vivo has been disputed. Here, we profile these molecular events using a single-molecule fluorescence assay to clarify the timings of RF3 binding and ribosome intersubunit rotation that trigger class-I RF dissociation, GTP hydrolysis, and RF3 dissociation. These findings in conjunction with quantitative modeling of intracellular termination flows reveal rapid ribosome-dependent guanine nucleotide exchange to be crucial for RF3 action in vivo.
What Are the Effective Components of Group-Based Treatment Programs For Smoking Cessation? A Systematic Review and Meta-Analysis
Authors: Mersha Amanual Getnet , Bryant Jamie , Rahman Tabassum , McGuffog Romany , Maddox Raglan , Kennedy Michelle
Published: April 2023

Introduction

There is significant variation in the format and delivery of group-based smoking cessation programs. To guide research and healthcare program implementation, it is important to understand the active components of interventions.

Aims and Methods

This review aimed to (1) identify behavior change techniques (BCTs) used in effective group-based smoking cessation interventions, (2) determine the effectiveness of group-based smoking cessation interventions on smoking cessation at 6-month follow-up, and (3) identify the behavior change techniques (BCTs) related to effective group-based smoking cessation. The following databases were searched in January 2000 and March 2022: MEDLINE, EMBASE, CINAHL, PsycINFO, The Cochrane Library, and Web of Science. BCTs used in each study were extracted using the BCT Taxonomy. Studies that included identified BCTs were computed, and meta-analyses were conducted to evaluate smoking cessation at 6-month follow-up.

Results

A total of 28 BCTs were identified from 19 randomized controlled trials. Studies included an average of 5.42 ± 2.0 BCTs. The most frequent BCTs were “information about health consequences” and “problem solving.” The pooled 6-month smoking cessation was higher in the group-based intervention group (OR = 1.75, 95% CI = 1.12 to 2.72, p <.001). Inclusion of the following four BCTs: “Problem solving,” “Information about health Consequences,” “Information about social and environmental consequences,” and “Reward (outcome)” were found to be significantly associated with increased rate of 6-month smoking cessation.

Conclusions

Group-based smoking cessation interventions doubles the rate of smoking cessation at 6-month follow-up. Implementing group-based smoking cessation programs, that incorporate multiple BCTs, is recommended for an effective smoking cessation care.

Implications

Group-based smoking cessation programs improves smoking cessation outcomes in clinical trials. There is a need to incorporate effective individual BCTs techniques to enhance smoking cessation treatment outcomes. A robust evaluation is required to assess the effectiveness of group-based cessation programs in real world settings. There is also a need to consider the differential effectiveness of group-based programs and BCT impacts on populations, for example, indigenous peoples.
Duration–response association between occupational exposure and pancreatic cancer risk: meta-analysis
Authors: Boonhat H , Pratama A P , Lin J-T , Lin R-T
Published: April 2023

Background

Evidence is lacking on the occupational exposure time window to chemical agents related to pancreatic cancer risk.

Aims

This study performed meta-regression and meta-analysis to examine the dose–response association between occupational exposure duration to chemical agents and pancreatic cancer risk.

Methods

We searched and reviewed studies on exposure duration and pancreatic cancer in five databases (Cochrane Library, EMBASE, PubMed, ScienceDirect and Web of Science) from inception to 16 May 2022. Exposure refers to the years a worker was exposed to any chemical agent, and outcome variables were pancreatic cancer incidence and mortality.

Results

We identified 31 studies, including 288 389 participants. In the meta-regression, the positive dose–response association indicated pancreatic cancer risk increased slightly with every additional year of exposure duration (slope = 1.01; 95% confidence interval [CI] 1.00–1.02). Pancreatic cancer risk increased with an exposure duration of 1–10 (relative risk [RR] = 1.04; 95% CI 1.02–1.06), 11–20 (RR = 1.11; 95% CI 1.05–1.16), and 21–30 years (RR = 1.39; 95% CI 1.12–1.73).

Conclusions

Pancreatic cancer risk increased as occupational exposure duration increased, with an exposure time window ranging from 1 to 30 years.
Policing the streets of New York City during the COVID pandemic: With a comparative angle
Authors: Haberfeld Maria (Maki) , Cheloukhine Serguei , Herrmann Christopher , Schneider John
Published: April 2023

New York City, known as ‘the city that never sleeps’, was taken by surprise by the total lockdown, imposed on its residents in March 2020 as a result of the ongoing COVID pandemic. To say that nobody was prepared for this type of extreme lockdown is an understatement. The enforcement of the requirements to wear masks in public and the prohibition of outside gathering was placed on the New York City Police Department (NYPD). The NYPD appeared to be as unprepared for this new monitoring and enforcement role much as any other governmental institution. In addition to the pandemic, a wave of anti-police sentiments swept the USA, including New York City, leaving the NYPD exposed to violent demonstrations and lootings.
Dobbs, American Federalism, and State Abortion Policymaking: Restrictive Policies Alongside Expansion of Reproductive Rights
Authors: Mayer Martin K , Morris John C , Aistrup Joseph A , Anderson R Bruce , Kenter Robert C
Published: April 2023

The U.S. Supreme Court’s June 2022 decision in Dobbs v. Jackson Women's Health Organization overturning Roe v. Wade shifted abortion-policy decision-making from the national level to the state level and opened the door for states to individually determine the level of protection for reproductive rights. We examine state actions following Dobbs and discuss the near-term implications of the decision for federalism and state governments. One effect of the Dobbs decision, evident in actions taken by some state legislatures, has been to open a window for states to enact laws imposing greater limits on reproductive options for women. However, another effect of Dobbs has been to create a greater demand for confirming and in some cases expanding reproductive rights, as seen by state constitutional amendments, supreme court decisions, and statutes protecting reproductive rights and safeguarding access to abortion services.
Correction of T-Cell Repertoire and Autoimmune Diabetes in NOD Mice by Non-myeloablative T-Cell Depleted Allogeneic HSCT
Authors: Sidlik Muskatel Rakefet , Nathansohn-Levi Bar , Reich-Zeliger Shlomit , Mark Michal , Stoler-Barak Liat , Rosen Chava , Milman-Krentsis Irit , Bachar Lustig Esther , Pete Gale Robert , Friedman Nir , Reisner Yair
Published: April 2023

The induction of partial tolerance toward pancreatic autoantigens in the treatment of type 1 diabetes mellitus (T1DM) can be attained by autologous hematopoietic stem cell transplantation (HSCT). However, most patients treated by autologous HSCT eventually relapse. Furthermore, allogeneic HSCT which could potentially provide a durable non-autoimmune T-cell receptor (TCR) repertoire is associated with a substantial risk for transplant-related mortality. We have previously demonstrated an effective approach for attaining engraftment without graft versus host disease (GVHD) of allogeneic T-cell depleted HSCT, following non-myeloablative conditioning, using donor-derived anti-3rd party central memory CD8 veto T cells (Tcm). In the present study, we investigated the ability of this relatively safe transplant modality to eliminate autoimmune T-cell clones in the NOD mouse model which spontaneously develop T1DM. Our results demonstrate that using this approach, marked durable chimerism is attained, without any transplant-related mortality, and with a very high rate of diabetes prevention. TCR sequencing of transplanted mice showed profound changes in the T-cell repertoire and decrease in the prevalence of specific autoimmune T-cell clones directed against pancreatic antigens. This approach could be considered as strategy to treat people destined to develop T1DM but with residual beta cell function, or as a platform for prevention of beta cell destruction after transplantation of allogenic beta cells.
Overexpression of ThSCL32 confers salt stress tolerance by enhancing ThPHD3 gene expression in Tamarix hispida
Authors: Lei Xiaojin , Fang Jiaru , Lv JiaXin , Li Zhengyang , Liu Zhongyuan , Wang Yucheng , Wang Chao , Gao Caiqiu
Published: April 2023

GRAS transcription factors belong to the plant-specific protein family. They are not only involved in plant growth and development but also in plant responses to a variety of abiotic stresses. However, to date, the SCL32(SCARECROW-like 32) gene conferring the desired resistance to salt stresses has not been reported in plants. Here, ThSCL32, a homologous gene of ArabidopsisthalianaAtSCL32, was identified. ThSCL32 was highly induced by salt stress in Tamarix hispida. ThSCL32 overexpression in T. hispida gave rise to improved salt tolerance. ThSCL32-silenced T. hispida plants were more sensitive to salt stress. RNA-seq analysis of transient transgenic T. hispida overexpressing ThSCL32 revealed significantly enhanced ThPHD3 (prolyl-4-hydroxylase domain 3 protein) gene expression. ChIP-PCR further verified that ThSCL32 probably binds to the novel cis-element SBS (ACGTTG) in the promoter of ThPHD3 to activate its expression. In brief, our results suggest that the ThSCL32 transcription factor is involved in salt tolerance in T. hispida by enhancing ThPHD3 expression.
A single-center experience of early administration of tocilizumab and corticosteroids in patients with COVID-19 pneumonia
Authors: Milošević Ivana , Barać Aleksandra , Jovanović Jaroslava , Vujović Ankica , Stevanović Goran , Todorović Nevena , Milošević Branko
Published: April 2023

Background

We investigated the therapeutic response of tocilizumab (TCZ) therapy in patients with coronavirus disease 2019 (COVID-19) pneumonia.

Methods

This observational retrospective study included 205 patients with confirmed COVID-19 pneumonia with SpO2˂93% and a markedly increased level of at least two biomarkers of inflammation. The TCZ was given in combination with corticosteroids. Clinical and laboratory results were analyzed and compared before TCZ therapy and 7 d after.

Results

The mean value of C-reactive protein (CRP) was significantly lower (p=0.001) on the seventh day after administration of TCZ compared with before (10.7 and 173.6 mg/L, respectively). Only in 9/205 (4.3%) patients, the CRP level did not decrease during the week-long period, and this was related to disease progression. The mean level of interleukin-6 before TCZ administration was 88±113 pg/mL, while after it was 32.7±21.7 pg/mL (p=0.01). After 7 d of TCZ therapy, almost 50% of patients who needed high-flow oxygen or ventilation support started to receive low-flow oxygen, while 73/205 (35.6%) patients who received low-flow oxygen before TCZ administration did not receive further oxygen support anymore (p=0.001). Although they received TCZ treatment, 38/205 (18.5%) severely sick patients died.

Conclusions

Tocilizumab improves clinical outcomes in hospitalized COVID-19 patients. These advantages were evident independent of the patient's comorbidities and were in addition to the advantages of systemic corticosteroids. In COVID-19 patients at risk of cytokine storms, TCZ appears to be an effective therapy choice.
Anterior Total Hip Arthroplasty With Gluteus Medius Repair: A Novel Technique
Authors: Schwarzman Garrett R. , Vesperman Reece I. , Mai Matthew C.
Published: April 2023

Introduction:

Proper function of the gluteus medius muscle is crucial to performance and outcomes following total hip arthroplasty. Gluteus medius tears are reported in up to 20% of patients undergoing hip replacements. The combination of increasing notoriety for the direct anterior approach and the potential for improved patient outcomes necessitates a technique to address gluteus medius tears in conjunction with total hip arthroplasty. Therefore, we present the following novel technique for transtendinous gluteus medius repair in conjunction with a direct anterior approach for total hip arthroplasty.

Technique:

The patient is placed supine with the operative leg in slight external rotation. An incision is made to the fascia overlying the tensor fascia latae. Blunt dissection is performed to the tensor fascia latae-sartorius interval. The deep rectus fascia is split, identifying the anterior capsule. Arthroplasty is then performed in the usual manner. Once the arthroplasty is completed, the hip capsule is closed, and the gluteus medius is exposed through an anterolateral approach. Once found, the tear is classified. A split in line with the tendon fibers is made in the mid aspect of the tear. Once visualized, the greater trochanter is decorticated, and suture anchors are placed. Sutures are passed and tied sequentially from distal to proximal.

Expected Outcomes:

Gluteus medius repair patients experience excellent outcomes, with multiple studies showing decreased pain and restoration in the strength of the abductor complex. In the setting of total hip arthroplasty, most patients display adequate abductor strength and no Trendelenburg gait at 5 years postoperative.
Association of the etiology and peak level of markedly elevated aminotransferases with mortality: a multicenter study
Authors: Kwak Ji Yoon , Kim Hyun-gyu , Han Ji Hee , Jeon Hankyu , Cha Ra Ri , Lee Sang Soo
Published: April 2023

Background:

Markedly elevated aminotransferase levels are commonly encountered among hospitalized patients. However, data regarding the trajectory of enzyme elevation and disease-specific prognosis are limited.

Methods:

This study included 3237 patients with at least one episode of aspartate aminotransferase or alanine aminotransferase level being higher than 400 U/L between January 2010 and December 2019 at 2 centers. Patients were classified into 5 groups comprising 13 diseases according to etiology. Factors associated with 30-day mortality were evaluated using a logistic regression analysis.

Results:

The most common disease leading to markedly elevated aminotransferase level was ischemic hepatitis (33.7%), followed by pancreatobiliary disease (19.9%), DILI (12.0%), malignancy (10.8%), and viral hepatitis (7.0%). The 30-day all-cause mortality rate was 21.6%. The mortality rate for patients from the pancreatobiliary, hepatocellular, extrahepatic, malignancy, and ischemic hepatitis groups was 1.7%, 3.2%, 13.8%, 39.9%, and 44.2%, respectively. Age, etiology, and peak aminotransferase levels were independently associated with 30-day mortality.

Conclusions:

In patients with markedly elevated liver enzymes, the etiology and peak AST level are significantly associated with mortality.
Multimodal hypersensitivity derived from quantitative sensory testing predicts pelvic pain outcome: an observational cohort study
Authors: Kmiecik Matthew J. , Tu Frank F. , Clauw Daniel J. , Hellman Kevin M.
Published: April 2023

Multimodal hypersensitivity (MMH)—greater sensitivity across multiple sensory modalities (eg, light, sound, temperature, pressure)—is associated with the development of chronic pain. However, previous MMH studies are restricted given their reliance on self-reported questionnaires, narrow use of multimodal sensory testing, or limited follow-up. We conducted multimodal sensory testing on an observational cohort of 200 reproductive-aged women, including those at elevated risk for chronic pelvic pain conditions and pain-free controls. Multimodal sensory testing included visual, auditory, and bodily pressure, pelvic pressure, thermal, and bladder pain testing. Self-reported pelvic pain was examined over 4 years. A principal component analysis of sensory testing measures resulted in 3 orthogonal factors that explained 43% of the variance: MMH, pressure pain stimulus response, and bladder hypersensitivity. The MMH and bladder hypersensitivity factors correlated with baseline self-reported menstrual pain, genitourinary symptoms, depression, anxiety, and health. Over time, MMH increasingly predicted pelvic pain and was the only component to predict outcome 4 years later, even when adjusted for baseline pelvic pain. Multimodal hypersensitivity was a better predictor of pelvic pain outcome than a questionnaire-based assessment of generalized sensory sensitivity. These results suggest that MMHs overarching neural mechanisms convey more substantial long-term risk for pelvic pain than variation in individual sensory modalities. Further research on the modifiability of MMH could inform future treatment developments in chronic pain.