bluuebunny/crossref_metadata_2025 huggingface dataset:
Transgenic murine models for the study of drug hypersensitivity reactions linked to HLA-I molecules
Authors: Puig Montserrat , Norcross Michael A.
Published: June 2023

Purpose of review

Immune-mediated drug hypersensitivity reactions (DHRs) can be life-threatening and an impediment to drug development. Mechanism of disease studies are difficult to perform in humans. Here we review human leukocyte antigens class I (HLA-I) transgenic murine models and highlight how these systems have helped to elucidate drug-specific and host immune factors that initiate, propagate and control severe drug toxicities to skin and liver.

Recent findings

HLA transgenic mice have been developed and used to study immune-mediated drug reactions in vitro and in vivo. CD8+ T cells from HLA-B∗57:01-expressing mice respond strongly to abacavir (ABC) in vitro but have self-limited responses to drug exposure in vivo. Immune tolerance can be overcome by depleting regulatory T cells (Treg) allowing antigen-presenting dendritic cells to express CD80/86 costimulatory molecules and signal through CD28 on the CD8+ T cell. Depletion of Treg also removes competition for interleukin 2 (IL-2) to allow T cell expansion and differentiation. Fine tuning of responses depends on inhibitory checkpoint molecules such as PD-1. Improved mouse models express only HLA in the absence of PD-1. These models show enhanced liver injury to flucloxacillin (FLX) which depends on drug priming, CD4+ T cell depletion, and lack of PD-1 expression. Drug-specific HLA-restricted cytotoxic CD8+ T cells can infiltrate the liver but are suppressed by Kupffer and liver sinusoidal endothelial cells.

HLA-I transgenic mouse models are now available to study ABC, FLX and carbamazepine-induced adverse reactions. In vivo studies range from characterizing drug-antigen presentation, T cell activation, immune-regulatory molecules and cell-cell interaction pathways that are specifically involved in causing or controlling unwanted DHRs.
Quantifying the impact of the coronavirus 2019 pandemic on youth sports-related injuries in the USA
Authors: Oganezova Karina , Houlihan Nathan , Maguire Kathleen J. , Lawrence John T. , Ganley Theodore J. , Williams Brendan A.
Published: June 2023

The purpose of this study was to estimate monthly and annual trends in youth sports-related injury over the years 2016–2020 using the National Electronic Injury Surveillance System (NEISS) database to measure the impact of COVID-19 on overall and sport-specific rates of injury. Children and adolescents (0–19 years) presenting to USA emergency departments with sport participation injury from 2016 to 2020 were identified. Descriptive statistical analyses were performed of injury patterns. An interrupted time series analysis was applied to estimate changes in injury trends during COVID-19. Proportional changes in injury characteristics during this period were examined. An estimated 5 078 490 sports-related injuries were identified with an annual incidence of 1406 injuries per 100 000 population. Seasonal peaks in injuries occurred during September and May. About 58% of injuries were associated with contact sports, such as basketball, football, and soccer, and the most common injuries were sprains and strains. After the pandemic onset, there was a statistically significant 59% decrease in national youth sports-related injuries compared with the average estimates for 2016–2019. While the distribution of injury characteristics did not appear to change, the location of injury appeared to shift away from school toward alternative settings. A significant reduction in youth sports-related injuries was identified in 2020 coinciding with the COVID-19 pandemic, persisting throughout the rest of the year. No changes in the anatomic or demographic distribution of injuries were identified. This study expands our epidemiologic understanding of youth sports-related injury trends and how they changed following the pandemic onset.
Accuracy of the hexapod external fixator in treating tibial angular deformities with or without limb length discrepancy: a retrospective study
Authors: Danişman Murat , Yilmaz Engin Türkay , Özdemir Erdi , Tuncay Ozan , Yilmaz Güney
Published: June 2023

Objective

Hexapod external fixator systems allow simultaneous deformity correction in multiple planes as well as limb lengthening. The aim of this study is to evaluate the accuracy of a hexapod frame (smart correction frame) in different types of tibial deformities requiring correction with or without lengthening.

Methods

A total of 54 tibial angular deformities and limb length discrepancies operated with a hexapod frame between January 2015 and January 2021 were classified into four groups: “Group A (n = 13): only lengthening,” “Group B (n = 14): lengthening and uniplanar correction,” “Group C (n = 16): only uniplanar correction,” and “Group D (n = 11): biplanar correction.” The accuracy of angular deformity correction/lengthening was calculated by dividing the actual correction/lengthening achieved after frame removal by the preoperative planned lengthening/correction.

Results

The lengthening accuracy in Group A and Group B was 96.3 ± 7.1% and 95.7 ± 5.9%, respectively (P = 0.685). The angular deformity correction accuracy was 85.1 ± 9.9% for Group B, 85.2 ± 13.9% for Group C, and 80.2 ± 18.4% for Group D (P = 0.852). A revision program was performed in six cases (1 in Group B, 1 in Group C, and 4 in Group D) for full correction of the deformities.

Conclusion

The accuracy of tibial lengthening is high with the hexapod frame and is minimally affected by simultaneous deformity correction; however, the accuracy of angular correction slightly reduces as the deformity becomes more complex. Surgeons should be aware that reprogramming may be required after complex deformity correction.
Is spinal height gain associated with rod orientation and the use of cross-links in magnetically controlled growing rods in early-onset scoliosis?
Authors: Hosseini Pooria , Akbarnia Behrooz A. , Pawelek Jeff B. , Tran Stacie , Zhang Justin , Johnston Charles E. , Shah Suken A. , Emans John B. , Mundis Gregory M. , Yaszay Burt , Samdani Amer F. , Sponseller Paul D. , Sturm Peter F. ,   Pediatric Spine Study Group
Published: June 2023

Optimal orientation for magnetically controlled growing rods (MCGRs) is unclear. The objective of this study was to investigate associations of rod orientation with implant-related complications (IRCs) and spinal height gains. Using an international early-onset scoliosis (EOS) database, we retrospectively reviewed 57 patients treated with dual MCGRs from May 2013 to July 2015 with minimum 2-year follow-up. Outcomes of interest were IRCs and left/right rod length gains and thoracic (T1–T12) and spinal (T1–S1) heights. We compared patients with two rods lengthened in the cephalad (standard; n = 18) versus opposite (offset; n = 39) directions. Groups did not differ in age, sex, BMI, duration of follow-up, EOS cause, ambulatory status, primary curve magnitude, baseline thoracic height, or number of distractions/year. We compared patients whose constructs used ≥1 cross-link (CL group; n = 22) versus no CLs (NCL group; n = 35), analyzing thoracic height gains per distraction (α = 0.05). Offset and standard groups did not differ in left or right rod length gains overall or per year or in thoracic or spinal height gain. Per distraction, the CL and NCL groups did not differ significantly in left or right rod length or thoracic or spinal height gain. Complications did not differ significantly between rod orientation groups or between CL groups. MCGR orientation and presence of cross-links were not associated with differences in rod length gain, thoracic height, spinal height, or IRCs at 2-year follow-up. Surgeons should feel comfortable using either MCGR orientation. Level of evidence: 3, retrospective.
Content Validation of a Questionnaire to Measure Digital Competence of Nurses in Clinical Practice
Authors: Golz Christoph , Hahn Sabine , Zwakhalen Sandra M.G.
Published: June 2023

Clinical practice nurses need adequate digital competence to use technologies appropriately at work. Questionnaires measuring clinical practice nurses' digital competence lack content validity because attitude is not included as a measure of digital competence. The aim of the current study was to identify items for an item pool of a questionnaire to measure clinical practice nurses' digital competence and to evaluate the content validity. A normative Delphi study was conducted, and the content validity index on item and scale levels was calculated. In each round, 21 to 24 panelists (medical informatics specialists, nurse informatics specialists, digital managers, and researchers) were asked to rate the items on a 4-point Likert scale ranging from “not relevant” to “very relevant.” Within three rounds, the panelists reached high consensus and rated 26 items of the initial 37 items as relevant. The average content validity index of 0.95 (SD, 0.07) demonstrates that the item pool showed high content validity. The final item pool included items to measure knowledge, skills, and attitude. The items included represent the international recommendations of core competences for clinical nursing. Future research should conduct psychometric testing for construct validity and internal consistency of the generated item pool.
Ranking the Critical Success Factors for Hospital Information Systems Using a Fuzzy Analytical Hierarchy Process
Authors: Arpaci Ibrahim , Ghazisaeedi Marjan , Esmaeilzadeh Firooz , Barzegari Reza , Barzegari Saeed
Published: June 2023

The design, development, and maintenance of hospital information systems face major challenges, which ultimately cause failures of these information systems. This study aimed to identify and rank critical success factors for hospital information systems by applying a fuzzy analytical hierarchy process. Potential critical success factors that could contribute to the success of hospital information systems were identified and extracted through a systematic review of the relevant studies. A questionnaire containing the critical success factors was designed and distributed to 250 hospital information system professionals. The hierarchical structure of the critical success factors was defined by using an exploratory factor analysis, and pairwise comparison matrices of the fuzzy analytical hierarchy process model were designed based on the identified factor structure. As a result, 50 potential critical success factors were extracted from 21 articles, and their content validity and face validity were assessed by the experts. Based on the exploratory factor analysis results, 36 critical success factors were classified into seven dimensions: organizational fitness, user-friendliness, maintainability, portability, productivity, reliability, and organizational and external support. The fuzzy analytical hierarchy process results indicated that reliability, user-friendliness, and organizational fitness (with 20.3, 19.9, and 18 points, respectively) had the greatest impact on the success of hospital information systems. The findings revealed that managers and policymakers should consider these critical success factors in designing and developing hospital information systems.
Copper homeostasis dysregulation promoting cell damage and the association with liver diseases
Authors: Liu Tao , Liu Yali , Zhang Feiyu , Gao Yanhang
Published: June 2023

Copper plays an important role in many metabolic activities in the human body. Copper level in the human body is in a state of dynamic equilibrium. Recent research on copper metabolism has revealed that copper dyshomeostasis can cause cell damage and induce or aggravate some diseases by affecting oxidative stress, proteasome, cuprotosis, and angiogenesis. The liver plays a central role in copper metabolism in the human body. Research conducted in recent years has unraveled the relationship between copper homeostasis and liver diseases. In this paper, we review the available evidence of the mechanism by which copper dyshomeostasis promotes cell damage and the development of liver diseases, and identify the future research priorities.
Neurobiology and long-term impact of bladder-filling pain in humans: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network study
Authors: Schrepf Andrew D. , Mawla Ishtiaq , Naliboff Bruce D. , Gallop Bob , Moldwin Robert M. , Tu Frank , Gupta Priyanka , Harte Steven , Krieger John N. , Yang Claire , Bradley Catherine , Rodriguez Larissa , Williams David , Magnotta Vincent , Ichesco Eric , Harris Richard E. , Clemens Quentin , Mullins Chris , Kutch Jason J.
Published: June 2023

Pain with bladder filling remains an unexplained clinical presentation with limited treatment options. Here, we aim to establish the clinical significance of bladder filling pain using a standardized test and the associated neural signature. We studied individuals diagnosed with urologic chronic pelvic pain syndrome (UCPPS) recruited as part of the multidisciplinary approach to the study of chronic pelvic pain (MAPP) study. Patients with urologic chronic pelvic pain syndrome (N = 429) and pain-free controls (N = 72) underwent a test in which they consumed 350 mL of water and then reported pain across an hour-long period at baseline and 6 months. We used latent class trajectory models of these pain ratings to define UCPPS subtypes at both baseline and 6 months. Magnetic resonance imaging of the brain postconsumption was used to examine neurobiologic differences between the subtypes. Healthcare utilization and symptom flare-ups were assessed over the following 18 months. Two distinct UCPPS subtypes were identified, one showing substantial pain related to bladder filling and another with little to no pain throughout the test. These distinct subtypes were seen at both baseline and 6 month timepoints. The UCPPS subtype with bladder-filling pain (BFP+) had altered morphology and increased functional activity in brain areas involved in sensory and pain processing. Bladder-filling pain positive status predicted increased symptom flare-ups and healthcare utilization over the subsequent 18 months when controlling for symptom severity and a self-reported history of bladder-filling pain. These results both highlight the importance of assessing bladder filling pain in heterogeneous populations and demonstrate that persistent bladder-filling pain profoundly affects the brain.
Job Stress and Sleep Disturbances Among Career Firefighters in Northern California
Authors: Chin Dal Lae , Odes Rachel , Hong OiSaeng
Published: June 2023

Object

This study examined the association between job stress and sleep disturbance among career firefighters.

Methods

A cross-sectional survey study was conducted with 154 career firefighters working in Northern California, US job stress was measured using the short form of the Effort-Reward Imbalance questionnaire and sleep was measured with the Patient-Reported Outcomes Measurement Information System Sleep Disturbance.

Results

Approximately 75% experienced sleep disturbance. For firefighters’ job stress, high effort (odds ratio [OR] = 3.68; 95% confidence interval [CI]: 1.25–10.80), high effort-reward ratio (OR = 3.55; 95% CI: 1.23–10.23), and high overcommitment (OR = 9.09; 95% CI: 2.30–35.85) were significantly associated with increased likelihood of sleep disturbance, after adjustment for other factors.

Conclusions

Job stress significantly affected firefighters’ sleep health, suggesting the need to design effective health promotion interventions to reduce job stress and improve sleep quality for these public service workers.
The Impact of COVID-19 on Physical Therapy Clinical Education Experiences in Florida
Authors: Svoboda Stephanie M. , Kostrna Jason , Pabian Patrick
Published: June 2023

Introduction.

Full-time clinical education experiences (CEEs) constitute a significant component of entry-level physical therapy education. COVID-19 challenged clinical education throughout the country by affecting the availability of CEEs.

Review of Literature.

Research suggested that the number of clinical education spots available would stay the same. By contrast, the number of students enrolling in physical therapist (PT) and physical therapist assistant (PTA) education programs continues to rise. In response to the COVID-19 pandemic, students and faculty expressed concerns about the lack of student readiness and the availability of CEEs. The purpose of this study was to examine prepandemic factors that influenced the number of CEE slots available in Florida and the impact that the COVID-19 pandemic had on slot availability. Furthermore, researchers sought to identify factors that prevented a return to prepandemic levels of CEE spot offerings and recognize solutions to overcome those barriers. Finally, the researchers aimed to pinpoint suggestions to enhance collaborations between the clinical sites and physical therapy education programs.

Subjects.

Forty-eight site coordinators of clinical education (SCCEs) from various settings and regions in Florida completed the survey.

Methods.

An online survey was distributed to Florida SCCEs to ascertain their perceptions on how COVID-19 influenced clinical education. The researchers used descriptive and inferential statistics to analyze the data.

Results.

Clinical instructor (CI) volunteerism was the primary determinant of CEE spots available before the COVID-19 pandemic. The number of CEE spots was reduced for both PT and PTA education programs during the COVID-19 pandemic. Although the PTA slots returned to their baseline from 2019, the PT placements remained significantly lower in 2021. Social distancing and CI availability had the most considerable impact on CEE offerings. Site coordinators of clinical education also suggested that the greatest supports needed from the academic institutions were educating students on COVID-19 prevention and providing personal protective equipment (PPE) to students for their CEEs. This article also offers suggested incentives that academic sites can provide their clinical partners, such as in-services earning continuing education units, to enhance their participation in clinical education.

Discussion and Conclusion.

All clinical education stakeholders must collaborate to provide students with the required clinical educational opportunities. Academic sites should continue to provide support, training, and incentives to CIs to enhance participation from clinical education sites. Educational programs must add content about COVID-19 to their curriculum and consider providing students with PPE during their rotations to restore the number of CEEs post-COVID-19 pandemic.
Magnetic Resonance Imaging in Patients with Cochlear Implants without Magnet Removal: A Radiology-Administered Protocol to Enhance Operational Efficiency and Improve Workflow
Authors: Johnson B. Jake , Macielak Robert J. , Watson Robert E. , Heimer Jean M. , Wiste Britany J. , Lane John I. , Edmonson Heidi A. , Carlson Matthew L.
Published: June 2023

Objective

To describe the development, implementation, and validation of a radiology-administered protocol to obtain magnetic resonance imaging (MRI) in patients with cochlear implants and auditory brainstem implants without magnet removal.

Study Design

Retrospective review and description of novel care pathway.

Methods

A radiology-administered protocol was designed based on careful input from the radiology safety committee and neurotology. Radiology technologist training modules, consent instructions, patient educational material, clinical audits, and other safeguards were implemented, with samples provided in this report. The primary outcomes measured included instances of magnet displacement during MRI and premature termination of MRI studies secondary to pain.

Results

Between June 19, 2018, and October 12, 2021, 301 implanted ears underwent MRI without magnet removal, including 153 devices housing diametric MRI-conditional magnets, and 148 implants with conventional axial (i.e., nondiametric) magnets. Among cases with diametric MRI-conditional magnets, all studies were completed without magnet dislodgement or need to terminate imaging early due to pain. Among cases with conventional axial (nondiametric) magnets, 29 (19.6%) MRI studies were stopped prematurely secondary to pain or discomfort; the overall rate of this event was 9.6% (29 of 301) among the entire study cohort. In addition, 6.1% (9 of 148) experienced confirmed magnet displacement despite headwrap placement; the overall rate among all cases was 3.0% (9 of 301). Eight of these patients received successful external magnet reseating through manual pressure on the external scalp without surgery, and one required surgical replacement of the magnet in the operating room. There were no documented instances of hematoma, infection, device or magnet extrusion, internal device movement (i.e., gross receiver-stimulator migration), or device malfunction in this cohort related to MRI.

Conclusions

We present the successful implementation of a radiology-administered protocol designed to streamline care for cochlear implant and auditory brainstem implant recipients who require MRI and ease clinical demands for otolaryngology providers. Examples of resources developed, including a process map, radiology training modules, consent instructions, patient educational materials, clinical audit, and other procedural safety measures are provided so interested groups may consider adapting and implementing related measures according to need.
Case Report of a Myeloid Neoplasm with Pathogenic Germline Variant in DDX41 and Constitutional inv(7)(q11.2q22) Along With JAK2 Pathogenic Variant in a 9-Year-old Patient Who Presented With Features of Essential Thrombocythemia
Authors: Gray Austin L. , Liu Yan , Wappler-Guzzetta Edina A. , Cherukuri Durga , Wang Jun , Jain Akshat
Published: June 2023

Germline pathogenic variants in DDX41 have recently been described in association with myelodysplastic syndrome and acute myeloid leukemia in older populations. However, this pathogenic variant has rarely been described in the pediatric population. This report represents a novel case of newly diagnosed myeloid neoplasm in a 9-year-old patient presenting with essential thrombocythemia-like features and was proven to have JAK2 V617F pathogenic variant, constitutional balanced paracentric inversion on q-arm of chromosome 7, and a germline heterozygous DDX41 pathogenic variant. This is the first reported case of a pediatric patient who presented with the constellation of these clinical features, histologic findings, and genetic alterations.
Epstein-Barr Virus-induced Paroxysmal Cold Hemoglobinuria in a 17-Year-old Male
Authors: Schmittau Kayla M. , Giordano Lisa
Published: June 2023

Paroxysmal cold hemoglobinuria is a rare autoimmune hemolytic anemia seen almost exclusively in children under 5 years of age after a viral illness. It is mediated by a biphasic polyclonal autoantibody against red blood cells, which causes severe hemolysis that typically self-resolves within 2 weeks without recurrence. While laboratory identification of the aforementioned antibody, the Donath Landsteiner antibody, would confirm this diagnosis, a negative test does not rule out this condition in the appropriate clinical context. We report on the rare occurrence of a severe presentation of paroxysmal cold hemoglobinuria in a 17-year-old male with Epstein-Barr virus infection.
Nutritional Supplementation for the Prevention of Muscle Atrophy in Older People
Authors: Edwards Hope , Jones Huw , Moseley Jamie , Marshall Thomas , El-Khamisy Sherif F. , Aung Myo Nyein , Farrow Matthew
Published: June 2023

Consuming adequate calories, protein, and micronutrients is vital for supporting muscle mass, muscle strength, and physical function as we age. Without sufficient nutrition, older people put themselves at an increased risk of developing sarcopenia. Therefore, in addition to weight-bearing exercise, nutritional supplementation may be important to ensure older individuals have good physical health. This review discusses the role of nutritional supplementation in maintaining muscle health in older people.
Practice of IDH1, ATRX, and P53 Immunohistochemistry in Integrated Diagnosis of Adult Diffuse Gliomas: Single Center Study
Authors: Shabanzadeh nejabad Zohreh , Mabroukzadeh kavari Hoda , Saffar Hana , Tavangar Seyed Mohammad , Sefidbakht Salma , Khoshnevisan Alireza , Zare-Mirzaie Ali , Vasei Mohammad , Jafari Ensieh , Yaghmaii Marjan , Saffar Hiva
Published: June 2023

Diffuse gliomas exhibit different molecular and genetic profiles with a wide range of heterogeneity and prognosis. Recently, molecular parameters including ATRX, P53, and IDH mutation status or absence or presence of 1p/19q co-deletion have become a crucial part of the diagnosis of diffuse glioma.

In the present study, we tried to analyze the routine practice of the above-mentioned molecular markers focusing on the IHC method in cases of adult diffuse gliomas to evaluate their utility in the integrated diagnosis of adult diffuse gliomas.

Totally, 134 cases of adult diffuse glioma were evaluated. Using the IHC method, 33,12, and 12 cases of IDH mutant Astrocytoma grade 2, 3, 4, and 45 cases of gliobalstoma, IDH wild type, were molecularly diagnosed. By adding the FISH study for 1p/19q co-deletion, 9 and 8 cases of oligodendroglioma grade 2 and 3 also were included. Two IDH mutant cases were negative for IDH1 in IHC but revealed a positive mutation in further molecular testing. Finally, we were not able to incorporate a complete integrated diagnosis in 16/134(11.94%) of cases. The main molecularly unclassified group was histologically high-grade diffuse glial tumors in patients less than 55 years old and negative IDH1 immunostaining. P53 was positive in 23/33 grade 2, 4/12 grade 3, and 7/12 grade 4 astrocytomas, respectively. Four out of 45 glioblastomas showed positive immunostain, and all oligodendrogliomas were negative.

In conclusion, a panel of IHC markers for IDH1 R132H, P53, and ATRX significantly improves the molecular classification of adult diffuse gliomas in daily practice and can be used as a tool to select limited cases for co-deletion testing in the low resources area.
Outcomes of Calvarial and Soft Tissue Reconstruction with Latissimus Dorsi Rib Osteomyocutaneous Free Flap
Authors: Bassiri Gharb Bahar , Meyers Abigail , Rezaei Majid , Figueroa Brian , Maasarani Samantha , Annunziata Michael , Nagel Sean , Bain Mark , Murthy Sudish , Rampazzo Antonio
Published: June 2023

Purpose:

The latissimus dorsi-rib osteomyocutaneous free flap (LDRF) has been used for autologous reconstruction of large composite calvarial and scalp defects. In this study, we aim to present clinical and patient-reported outcomes after LDRF reconstruction.

Methods:

An anatomical study was conducted to evaluate the distribution of the connecting perforators between the thoraco-dorsal and intercostal system. An IRB-approved retrospective review of ten patients who underwent LDRF and one or two ribs for treatment of cranial defects was conducted. Patient-reported outcomes regarding quality of life, neurological and functional status were evaluated using validated surveys. One-way analysis of variance (ANOVA) and post hoc Tukey’s tests were used for anatomical outcomes. Preoperative and postoperative scores were compared using paired t-tests.

Results:

The 10th rib (4.65± 2.01) followed by 9th rib (3.7±1.63) had the highest number of perforators. A combination of the 9 th and 11 th ribs exhibited maximal perforator number and pedicle length.

All patients had stable LDRF reconstructions. Eight patients completed both pre and postoperative questionnaires; Median clinical follow-up was 48 [34-70] months. Scores trended toward improvement but did not reach statistical significance on the Karnofsky Performance Scale (p=0.22), Functional Independence Measure (FIM; Motor p=0.52, Cognitive p=0.55), Headache Disability Index (p=0.38). The minimum clinically important difference (MCID) was surpassed, demonstrating improvement of function for 71% of patients on the Barthel Index and 63% on the Selective Functional Movement Assessment test.

Conclusion:

The LDRF can improve cognitive and physical functional status in complex patients with prior failed reconstructions for composite scalp and skull defects.
The Positive and Negative Predictive Value of Targeted Diagnostic Botox Injection in Nerve Decompression Migraine Surgery
Authors: ElHawary Hassan , Kavanagh Kaitlin , Janis Jeffrey E.
Published: June 2023

Introduction:

Nerve decompression surgery is an effective treatment modality for patients who suffer from migraines. Botulinum toxin type A (BOTOX) injections have been traditionally used as a method to identify trigger sites, however there is a paucity in data regarding its diagnostic efficacy. The goal of this study was to assess the diagnostic capacity of BOTOX in successfully identifying migraine trigger sites and predicting surgical success.

Methods:

A sensitivity analysis was performed on all patients receiving BOTOX for migraine trigger site localization followed by a surgical decompression of affected peripheral nerves. Positive and negative predictive values were calculated.

Results:

A total of 40 patients met our inclusion criteria and underwent targeted diagnostic BOTOX injection followed by a peripheral nerve deactivation surgery with at least three months follow-up. Patients with successful BOTOX injections (defined as at least 50% improvement in Migraine Headache Index (MHI) scores post injection) had significantly higher average reduction in migraine intensity (56.7% vs 25.8%; p=0.020, respectively), frequency (78.1% vs 46.8%; p=0.018, respectively), and MHI (89.7% vs 49.2%; p=0.016, respectively) post-surgical deactivation. Sensitivity analysis shows that the use of BOTOX injection as a diagnostic modality for migraine headaches has a sensitivity of 56.7% and a specificity of 80.0%. The positive predictive value is 89.5% and the negative predictive value is 38.1%.

Conclusion:

Diagnostic targeted BOTOX injections have a very high positive predictive value. It is therefore a useful diagnostic modality that can help identify migraine trigger sites and improve pre-operative patient selection.
“Bipedicled Scrotal Flap for Penile Resurfacing”
Authors: McLaughlin Mariel M , Abbassi Bahar , Pribaz Julian J
Published: June 2023

Background

Acquired penile defects can be secondary to various pathologies including infection, scar, or complications following urologic procedures. Penis defects with skin deficit carry a distinct challenge for reconstructive surgeons. Scrotal flaps can provide reliable coverage and can restore distinct qualities of native penile skin.

Methods

A series of patients presented with a variety of acquired penile defects. Each of these patients underwent staged bi-pedicled scrotal flaps for coverage by senior author.

Results

Eight patients underwent bi-pedicled scrotal flap reconstruction for penile defects with a skin deficit. All eight patients had satisfactory outcomes post operatively. Only two of the eight patients had minor complications.

Conclusions

For select patients presenting with underlying deficit of penile skin, bipedicle scrotal flaps prove to be a safe, reproducible, and reliable reconstructive technique for penile resurfacing.
The classification of the conjoined latissimus dorsi – groin flap and the indications for the four types of the flaps
Authors: Wu Cho-Han , Velazquez-Mujica Jonathan , Donfrancesco Andrea , Lee Jian-Jr , Chen Hung-Chi
Published: June 2023

The conjoined latissimus dorsi – groin flap is a versatile flap which can not only serve as osteocutaneous flap to provide large soft tissue and bone for reconstruction of extensive defects but also offer functioning muscle transfer and lymph nodes transfer for prevention of lymphedema following wide excision of tumors or major trauma. In the recent 24 years, we have classified the conjoined LD-groin flap into four categories and proposed precautions for application of the conjoined flaps.
Opioid-Sparing Protocol for Endocrine Surgery (OSPREY): A Prospective Study
Authors: Kligerman Maxwell P , Austerlitz Joaquin , Orloff Lisa A , Noel Julia E
Published: June 2023

Background:

Thyroid and parathyroid operations are amongst the most commonly performed surgeries in the world; however, there remains a paucity of prospective clinical trials evaluating the efficacy of opioid-sparing protocols following surgery.

Study Design:

This prospective non-randomized study was performed between March and October 2021. Participants self-selected their cohort of either an opioid-sparing protocol of acetaminophen/ibuprofen or a treatment-as-usual protocol with opioids. Primary endpoints were Overall Benefit of Analgesia Scores (OBAS) and opioid use as reported in daily medication logs. Data were recorded over seven days. Multivariable regression, pooled variance t-tests, Mann-Whitney test, and chi-square tests were used to evaluate the results.

Results:

A total of 87 participants were recruited; 48 participants opted for the opioid-sparing arm while 39 participants opted for the treatment as usual arm. Patients in the opioid-sparing arm used significantly less opioids (morphine equivalents 0.77 ± 1.71 vs. 3.34 ± 5.87, p=0.042) but had no significant difference in OBAS (p=0.37). Multivariable regression analysis demonstrated no significant difference in mean OBAS between treatment arms when controlling for age, sex, and type of surgery (p=0.88). There were no major adverse events in either group.

Conclusions:

An opioid-sparing treatment algorithm based on use of acetaminophen/ibuprofen may offer a safe and effective treatment algorithm compared to a primary opioid focused treatment pathway. Randomized adequately-powered studies are needed to confirm these findings.
William George Hill. 7 August 1940—17 December 2021
Authors: Mackay FRS Trudy F. C.
Published: June 2023

William (Bill) Hill was an internationally acclaimed statistical, population and quantitative geneticist. His work was inspired by practical problems in animal breeding, but is widely applicable to evolutionary biology and human genetics. Bill's work focused on the joint effects of linkage, mutation and genetic architecture in finite populations. He showed that linked loci under selection can interfere with each other, reducing the rate of response to selection. He derived a widely used metric for linkage disequilibrium and showed that there is likely to be substantial linkage disequilibrium between closely linked variants in finite populations. He also showed that the sampling variance of linkage disequilibrium is very large, hampering its use in estimating effective population size or recombination rates. Bill derived sampling variances for inbreeding and realized relatedness between individuals with the same expected degree of relatedness. He raised awareness about the importance of new mutations for quantitative genetic variation and the response to artificial selection, and developed models for the maintenance of quantitative genetic variation by a balance between mutation and stabilizing selection. His experimental designs for estimating heritability and conducting artificial selection experiments have been widely adopted, and were utilized in his own long-term mouse selection experiments. Bill influenced animal breeding directly through consultancies with breeding companies, and his influence on quantitative genetics continues today via his numerous mentees.
Microbial Changes occurring during oronasal fistula wound healing
Authors: Goudy Steven L. , Bradley Heath , Gacasan Camillo Anthony , Toma Afra , Naudin Crystal R. , Wuest William M. , Tomov Martin , Serpooshan Vahid , Coskun Ahmet , Jones Rheinallt M.
Published: June 2023

The oral microbiome is a complex community that matures with dental development while oral health is also a recognized risk factor for systemic disease. Despite the oral cavity having a substantial microbial burden, healing of superficial oral wounds occurs quickly and with little scarring. By contrast, creation of an oro-nasal fistula (ONF), often occurring after surgery to correct a cleft palate, is a significant wound healing challenge that is further complicated by a connection of the oral and nasal microbiome. In this study, we characterized the changes in the oral microbiome of mice following a freshly inflicted wound in the oral palate that results in an open and unhealed ONF. Creation of an ONF in mice significantly lowered oral microbiome alpha diversity, with concurrent blooms ofEnterococcus faecalis, Staphylococcus lentus, and Staphylococcus xylosusin the oral cavity. Treatment of mice with oral antibiotics one week prior to ONF infliction resulted in a reduction in the alpha diversity, preventedE. faecalisandS. lentus, and S. xylosusblooms, but did not impact ONF healing. Strikingly, delivery of the beneficial microbeLactococcus lactissubsp. cremoris (LLC) to the wound bed of the freshly inflicted ONF via a PEG-MAL hydrogel vehicle resulted in rapid healing of the ONF. Healing of the ONF was associated with the maintenance of relatively high microbiome alpha diversity, and limited the abundance ofE. faecalisandS. lentus, and S. xylosusin the oral cavity. These data demonstrate that a freshly inflicted ONF in the murine palate is associated with a dysbiotic oral microbiome state that may prevent ONF healing, and a bloom of opportunistic pathogens. The data also demonstrate that delivery of a specific beneficial microbe, LLC, to the ONF can boost wound healing, can restore and/or preserve oral microbiome diversity, and inhibit blooms of opportunistic pathogens.
Species and habitat specific changes in bird activity in an urban environment during Covid 19 lockdown
Authors: Sun Congnan , Hassin Yoel , Boonman Arjan , Shwartz Assaf , Yovel Yossi
Published: June 2023

Covid-19 lockdowns provided ecologists with a rare opportunity to examine how animals behave when humans are absent. Indeed many,sometimes contradicting, studies reported various effects of lockdowns on animal activity, especially in urban areas and other human-dominated habitats. We explored how Covid-19 lockdowns in Israel have influenced bird activity in an urban environment by using continuous acoustic recordings to monitor three common bird species that differ in their level of adaptation to the urban ecosystem: (1) the hooded crow, an urban exploiter, which depends heavily on anthropogenic resources; (2) the rose-ringed parakeet, an invasive alien species that has adapted to exploit human resources; and (3) the graceful prinia, an urban adapter, which is relatively shy of humansandcan be found urban habitats with shrubs and prairies. Acoustic recordings provided continuous monitoring of bird activity without an effect of the observer on the animal. We performed dense sampling of a 1.3 square km area in northern Tel-Aviv by placing 17 recorders for more than a month in different micro-habitats within this region including roads, residential areas and urban parks. We monitored both lockdown and no-lockdown periods. We portray a complex dynamic system where the activity of specific bird speciesdepended on many environmental parameters anddecreases or increases in a habitat-dependent manner during lockdown. Specifically, urban exploiter species decreased their activity in most urban habitats during lockdown, while human adapter species increased their activity during lockdown especially in parks where humans were absent. Our results also demonstrate the value of different habitats within urban environments for animal activity, specifically highlighting the importance of urban parks. These species- and habitat-specific changes in activity might explain the contradicting results reported by others who have not performed a habitat specific analysis.
Comodulation reduces interindividual variability of circuit output
Authors: Schneider Anna C. , Itani Omar , Cronin Elizabeth , Daur Nelly , Bucher Dirk , Nadim Farzan
Published: June 2023

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Ionic current levels of identified neurons vary substantially across individual animals. Yet, under similar conditions, neural circuit output can be remarkably similar, as evidenced in many motor systems. All neural circuits are influenced by multiple neuromodulators which provide flexibility to their output. These neuromodulators often overlap in their actions by modulating the same channel type or synapse, yet have neuron-specific actions resulting from distinct receptor expression. Because of this different receptor expression pattern, in the presence of multiple convergent neuromodulators, a common downstream target would be activated more uniformly in circuit neurons across individuals. We therefore propose that a baseline tonic (non-saturating) level of comodulation by convergent neuromodulators can reduce interindividual variability of circuit output. We tested this hypothesis in the pyloric circuit of the crab,Cancer borealis. Multiple excitatory neuropeptides converge to activate the same voltage-gated current in this circuit, but different subsets of pyloric neurons have receptors for each peptide. We quantified the interindividual variability of the unmodulated pyloric circuit output by measuring the activity phases, cycle frequency and intraburst spike number and frequency. We then examined the variability in the presence of different combinations and concentrations of three neuropeptides. We found that at mid-level concentration (30 nM) but not at near-threshold (1 nM) or saturating (1 μM) concentrations, comodulation by multiple neuropeptides reduced the circuit output variability. Notably, the interindividual variability of response properties of an isolated neuron was not reduced by comodulation, suggesting that the reduction of output variability may emerge as a network effect.

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Significance Statement

Neuromodulation has been explored as a mechanism to provide flexibility to the output of neural circuits. All neural circuits are subject to neuromodulation by multiple substances. Here, we propose a different but complimentary role for neuromodulation. We use two general facts about neuromodulation to show that convergent comodulation at tonic mid-concentration levels reduces interindividual variability of neural circuit output. These facts are that 1) Multiple neuromodulators can have convergent actions on the same subcellular substrates and 2) Neurons express different neuromodulator receptors at different levels.
Brain-wide neural recordings in mice navigating physical spaces enabled by a cranial exoskeleton
Authors: Hope James , Beckerle Travis , Cheng Pin-Hao , Viavattine Zoey , Feldkamp Michael , Fausner Skylar , Saxena Kapil , Ko Eunsong , Hryb Ihor , Carter Russell , Ebner Timothy , Kodandaramaiah Suhasa
Published: June 2023

Complex behaviors are mediated by neural computations occurring throughout the brain. In recent years, tremendous progress has been made in developing technologies that can record neural activity at cellular resolution at multiple spatial and temporal scales. However, these technologies are primarily designed for studying the mammalian brain during head fixation – wherein the behavior of the animal is highly constrained. Miniaturized devices for studying neural activity in freely behaving animals are largely confined to recording from small brain regions owing to performance limitations. We present a cranial exoskeleton that assists mice in maneuvering neural recording headstages that are orders of magnitude larger and heavier than the mice, while they navigate physical behavioral environments. Force sensors embedded within the headstage are used to detect the mouse’s milli-Newton scale cranial forces which then control the x, y, and yaw motion of the exoskeleton via an admittance controller. We discovered optimal controller tuning parameters that enable mice to locomote at physiologically realistic velocities and accelerations while maintaining natural walking gait. Mice maneuvering headstages weighing up to 1.5 kg can make turns, navigate 2D arenas, and perform a navigational decision-making task with the same performance as when freely behaving. We designed an imaging headstage and an electrophysiology headstage for the cranial exoskeleton to record brain-wide neural activity in mice navigating 2D arenas. The imaging headstage enabled recordings of Ca2+activity of 1000s of neurons distributed across the dorsal cortex. The electrophysiology headstage supported independent control of up to 4 silicon probes, enabling simultaneous recordings from 100s of neurons across multiple brain regions and multiple days. Cranial exoskeletons provide flexible platforms for largescale neural recording during the exploration of physical spaces, a critical new paradigm for unraveling the brain-wide neural mechanisms that control complex behavior.
New genomic techniques, old divides: stakeholder attitudes towards new biotechnology regulation in the EU and UK
Authors: Menary Jonathan , Fuller Sebastian S.
Published: June 2023

The European Union and United Kingdom are in the process of establishing new regulation regarding the use of new genomic techniques in crop and animal breeding. As part of this process, consultations have been launched to understand the views of stakeholders and the wider public towards the use of new genomic techniques in plant and animal breeding. The responsible research and innovation framework emphasises the importance of dialogue between technology developers and stakeholders, including the public, but what are the opinions of stakeholders towards the regulation of NGTs in Europe and do they view these consultations as opportunities to engage with technology governance?

We conducted semi-structured interviews with experts from a range of agri-food stakeholder groups in the European Union and United Kingdom to understand current attitudes towards new biotechnology regulation, how they viewed the process of consultation in both places and what influence they felt they had in shaping regulations. We found that the discussion is similar in both EU and UK, with predictable and fixed opinions determined by attitudes towards the perceived risks associated with direct mutagenesis.

Both UK and EU consultations were considered to have the same weaknesses and stakeholders discussed a desire for more dialogic forms of engagement. We highlight several options for new forms of involvement in biotechnology regulation by exploring relevant responsible research and innovation literature.