bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Prolonged Opioid Consumption in Lower Extremity Amputees
Authors: Park Rachel H. , Liston Jared M. , Samuel Ankhita R. , Forster Grace L. , DeGeorge Brent R.
Published: August 2023

Background:

Extremity amputation is a common procedure performed to treat a variety of different problems and affects quality of life in a number of ways. In addition to acute postoperative pain, amputations have been shown to cause chronic pain that is often neuropathic in many amputees. This study sought to better characterize the role of opioids in postoperative pain control in lower extremity amputees.

Methods:

Patients who underwent lower extremity amputation between 2010 and 2018 were identified in a national insurance-claims database using ICD-9, ICD-10, and CPT codes. Patient demographics, comorbidities, perioperative opioid use, and prolonged postoperative opioid use were then determined for both groups. Descriptive statistics and logistic regression analysis were utilized to evaluate the association of patient-related risk factors and neuropathic pain conditions with perioperative and prolonged postoperative opioid use.

Results:

In total, 2247 opioid-naive lower extremity amputees were identified. An estimated 54.7% of patients utilized opioids in the perioperative period, and 44.6% were found to have prolonged opioid use. Younger age (ages 40–50 versus older), history of chronic pain, migraines, lower back pain, Charlson Comorbidity Index greater than 1, preoperative benzodiazepine, muscle relaxant, anticonvulsant, and antidepressant use were all significantly related to prolonged postoperative opioid use.

Conclusions:

Prolonged postoperative opioid use is a problem that affects nearly half of lower extremity amputees and seems to be significantly related to the preoperative use of benzodiazepines, muscle relaxants, anticonvulsants, and antidepressants. Further research into the diagnosis and treatment of postamputation neuropathic pain is needed to prevent reliance on opioids in this patient population.
Reliability of Perforator-based UPM Flap for Coverage of Little Finger and Dorsal Hand Defect
Authors: Estawrow Mina A. , Gad Ahmed M.
Published: August 2023

Background:

There are different approaches for reconstruction of little finger and dorsal hand defects. The ulnar parametacarpal flap, first introduced by Backhach et al in 1995, is considered a good option for reconstructing such defects. In this study, we elevated this flap on one perforator and applied it as a propeller flap. We then discussed the reliability of this flap and which perforator (the proximal or the distal one) is more reliable.

Methods:

This study was carried out on 20 patients with different little finger and dorsal hand defects between June 2017 and March 2019. All defects were covered by perforator-based ulnar parametacarpal flaps. Ten flaps were based on the proximal perforator, whereas the other 10 were based on the distal perforator.

Results:

With a period of follow-up ranging from 6 months to 1 year, all flaps that were raised on the proximal perforator survived completely, whereas two of 10 flaps raised on the distal perforator showed venous congestion and also one flap showed partial necrosis of the distal one-third due to ischemia.

Conclusions:

The perforator based ulnar parametacarpal flap is a reliable option for reconstruction of little finger and dorsal hand defects. It is more reliable when it is raised on the proximal perforator rather than on the distal one.
Posterior Tibial Artery Perforator V-Y Advancement Flap for Small–Medium Size Lower Limb Defects
Authors: Almishal Obaid , Bin Mahmoud Asmaa Z. , Alshomer Feras M.
Published: August 2023

Background:

The posterior tibial artery perforator flap has been described as a good option for small to moderate lower extremity defects with consistent anatomy and caliber. Different geometrical designs are found in the literature for posterior tibial artery perforator flaps and are mostly executed as propeller, peninsular, and island flaps. Upon literature review, V-Y advancement flaps were not commonly used, despite the clear design, persistent anatomy, and straight execution. Our aim was to report our case series to present the validity of such design and the success of reconstruction.

Method:

Over 1 year, three cases were reconstructed successfully with posterior tibial artery perforator flaps with V-Y advancement design. Clinical evaluation was done for all patients as well as follow-up in the outpatient clinic until complete healing of the wounds was achieved. Multiple modifications were done intraoperatively to enhance flap reach and minimize the complications, including designing V-Y advancement flaps larger than the defect, careful perforator dissection, and finally, strict postoperative course.

Results:

All three cases healed completely with no complications. The average follow-up time in the clinic was 3 months.

Conclusions:

Posterior tibial artery perforator flap with V-Y advancement design is a viable option for reconstructing medium sized lower limb defects, but requires careful design and execution. The suggested steps will increase the survival of the flap and reconstruct the defect successfully.
Reported Pain in Cisgender Female and Transmasculine Patients Seeking Benign Breast Surgery
Authors: Ganor Oren , Almazan Anthony N. , Boskey Elizabeth R.
Published: August 2023

Background:

Benign breast surgery aims to treat the physical and psychological discomfort that may be associated with excess breast tissue. In this investigation, we present the first systematic examination and comparison of the determinants of pain and related symptomology in cisgender women and transmasculine individuals presenting for benign breast surgery.

Methods:

To complete this study, we abstracted the intake forms of 128 transmasculine and 62 cisgender female patients who presented for benign breast surgery between August 2016 and July 2020.

Results:

Increasing chest size was associated with significantly increased odds of reporting rash (OR 1.10 95% CI [1.01–1.10], P < 0.03), difficulty playing sports (OR 1.19 95% CI [1.09–1.29], P < 0.001), and difficulty finding clothes that fit (OR 1.21, 95% CI [1.11–1.33], P < 0.001). For individuals who bound their chests, size was also associated with difficulty exercising in a binder (OR 1.14 [1.01–1.29], P < 0.03). Looking separately at the two populations, the only factors that remained associated with pain in multivariate models were BMI (β = 0.10 [0.01–0.18], P < 0.03) for cisgender women and history of binding (β = 1.95 [0.37–3.52], P < 0.02) for transmasculine people.

Conclusions:

Pain does not seem to be associated with chest size in either cisgender female or transmasculine patients seeking benign breast surgery. The association between chest binding and pain in transmasculine people supports the provision of gender-affirming chest surgery to eliminate the need to bind and reduce both physical and psychological distress.
Atypical Hyperplasia Found Incidentally during Routine Breast Reduction Mammoplasty: Incidence and Management
Authors: Noorbakhsh Seth , Koenig Zachary A. , Hewitt Noah , Climov Mihail , Hazard-Jenkins Hannah , Flanagan Melina , Woodberry Kerri
Published: August 2023

Background:

Atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) of the breast are premalignant lesions. Although the literature on ADH and ALH as a whole is well-developed, research on ADH and ALH incidentally discovered during breast reduction is less robust.

Methods:

In this study, 355 patients undergoing bilateral reduction mammoplasty at West Virginia University were retrospectively reviewed. A variety of demographic and clinicopathologic variables were collected for each patient, and the incidence of atypical hyperplasia was calculated. Four patients (1.13%) were found to have atypical hyperplasia, three ALH, and one ADH, which is within the range reported in the literature. For patients incidentally found to have atypical hyperplasia, an in-depth analysis of postoperative management was performed.

Results:

Of the four patients with atypical hyperplasia, three were referred to a cancer center, and one patient followed only with plastic surgery. The three patients who were referred to a cancer center saw a breast surgeon, whereas the patient followed only by plastic surgery did not. None of the four patients received anti-estrogen therapy, but each patient who followed with a cancer center was offered treatment and declined.

Conclusions:

As a relatively uncommon finding with complex management guidelines, atypical hyperplasia discovered on breast reduction should be referred to a cancer center for long-term follow-up and management when possible. Further research is needed to assess if the management of atypical hyperplasia discovered incidentally after routine reduction should mimic treatment of atypical hyperplasia found after biopsy for suspicion of malignancy.
Routes to Residency: A National Survey Demonstrating the Pathways to Become a Plastic Surgeon
Authors: Stoehr Jenna R. , Applebaum Sarah A. , Ko Jason H. , Gosain Arun K.
Published: August 2023

Background:

Plastic and reconstructive surgery (PRS) residency training can be completed through multiple pathways. Current residents’ experiences regarding these different routes have not been previously described. The objective of the present study was to describe the educational pathways taken by current PRS residents in the United States. We hypothesized that there would be a small cohort of current PRS residents who were initially unsuccessful in matching into an integrated residency.

Methods:

An online survey was sent to PRS residents across all training years from October 2020 to January 2021. The survey collected information about residents’ match history, experience after not matching, and narrative comments on their route to residency. Public match data from the past 20 years (2001–2021) were also summarized with descriptive statistics.

Results:

One hundred seventy-four residents responded (response rate 15%; 174/1158). Of these, 133 applied to integrated programs as senior medical students, and 15 (11%) did not match after applying as a senior medical student. Unmatched applicants took multiple different routes to PRS, including participating in the Supplemental Offer and Acceptance Program, reapplying, transferring after some general surgery training, and completing an independent PRS residency. Three-fourths (76%) of independent program residents did not originally apply to the integrated match.

Conclusions:

An initial unsuccessful match result does not portend that one will not be able to train for a career in PRS. Our findings illustrate the potential routes to successful completion of PRS residency training, both for unmatched applicants and residents who develop later interest in PRS.
A Comparative Study of Mucosal Wound Healing after Excision with a Scalpel, Diode Laser, or CO2 Laser
Authors: Bilder Amir , Rachmiel Adi , Ginini Jiriys George , Capucha Tal , Ohayon Chaim , Weitman Efi , Emodi Omri
Published: August 2023

Background:

We aimed to compare the clinical and histological secondary healing effectiveness of various types of high-level laser versus scalpel excision in mucosa frenectomy.

Methods:

Forty-five Sprague Dawley rats were used in this study. These rats were divided into two laser intervention groups (CO2, n = 15; diode, n = 15) and one control group with scalpel excision (n = 15). The effectiveness of therapy has been assessed based on the comparison of intraoperative, postoperative, and histological parameters on days 7, 21, and 35, and postoperative weight changes as pain indicator.

Results:

Both laser groups demonstrated significantly (P < 0.05) less bleeding than did the control group during the intraoperative stage, whereas the CO2 laser showed more precise cutting compared with the diode laser (P < 0.05). The highest healing score was reported in the CO2 and scalpel groups on the first week of healing than in the diode group (P < 0.05). However, no significant difference was observed between the groups on days 21 and 35. Weight loss was significantly (P < 0.05) demonstrated in the diode group compared to the scalpel and CO2 groups till day 7. Both laser groups demonstrated delayed healing process compared with the scalpel. Nevertheless, the CO2 group followed the scalpel trends after day 7.

Conclusion:

Scalpel and CO2 laser yielded a superior clinical outcome compared with the diode excision of oral mucosa, whereby the CO2 has been proposed as the most effective laser type at the end of the first postoperative month.
Vascularized Fibular Grafts for Failed Liquid Nitrogen–treated Autografts in the Humerus: Report of Two Cases
Authors: Fujisawa Kou , Miyamoto Shimpei , Kobayashi Hiroshi , Okazaki Mutsumi
Published: August 2023

With advances in chemotherapy and surgical techniques, limb salvage and biological reconstruction, including autologous bone grafting, have become the preferred treatment options for primary malignant bone tumors of the extremities. Although autografts, which involve recycling of tumor-bearing bones, have the advantages of easy accessibility and anatomical matching, fracture is a frequent major complication. However, to our knowledge, salvage of refractory autograft failure has not yet been reported. This report describes free vascularized fibular graft implantation for salvaging failed previous reconstructions. We describe two patients (a 4-year-old girl and a 30-year-old man, respectively) with primary malignant bone tumors. Liquid nitrogen-treated autografts had been used to reconstruct the humerus in both cases. The patients sustained autograft fractures that could not be treated conservatively or by internal fixation. Free vascularized fibular grafts were transferred as double-barrel inlay grafts (length 7.2 and 8.2 cm) and a single-strut onlay graft (length 16 cm). The brachial arteries, brachial veins, and cephalic veins were used as recipient vessels. Bone union between the fibular grafts and humerus was achieved after 29 and 15 months of follow-up, respectively. In conclusion, free vascularized fibular grafts can be used to salvage refractory autograft fractures.
Auricular Protection after Ear Reconstruction Using an Antipressure Alarm
Authors: Liu Di , Su Xueshang , Hu Jintian
Published: August 2023

Auricular protection is an important part of postoperative care for ear reconstruction and has an important impact on the expected outcome of the surgery. Therefore, we developed an antipressure alarm to protect the reconstructed ear in the supine position. The device consists of three components: an alarm, a pressure detector, and an adjustable elastic band. When the patient is in a supine position, the pressure sensor is located above the back of the reconstructed ear. When the head is rotated to the affected side, the pressure detector senses the pressure signal in advance compared with the reconstructed ear, and then triggers an alarm to remind the patient to adjust his position in time to avoid pressing the reconstructed ear. The device has been applied to more than 100 patients and has achieved satisfactory clinical results.
Medial Pedicle Wise-pattern Breast Reduction for Gigantomastia: A Single-center Retrospective Review
Authors: Hinson Chandler , Bouillon Victoria , Brooks Ronald
Published: August 2023

Background:

Gigantomastia causes severe back pain, postural imbalance, intertrigo, and psychosocial disablement. Multiple breast reduction techniques exist. Breast reduction with free nipple graft reconstruction is the preferred treatment. We found that the medial pedicle Wise-pattern (MPWP) technique is an equally safe and effective technique.

Methods:

Review of our institution’s electronic medical record between February 2020 and February 2023 identified women with gigantomastia who underwent bilateral reduction with more than 1500 g resected in at least one breast. Multinomial logistical regressions were used to identify associations between comorbidities, operative techniques, postoperative complications, and nipple areolar complex function.

Results:

Thirty-one patients underwent bilateral reduction mammaplasty. Total bilateral resection weight and average body mass index (BMI) were 3828 g and 40 kg per m2. Common comorbidities were hypertension (38%) and tobacco use (26%). MPWP was used predominantly (65%), followed by inferior pedicle (16%) and superior-medial pedicle (10%). Complications included loss of nipple areolar complex sensation (23%) and wound dehiscence (16%). Reduction technique was not associated with increased surgical complications (odds ratio = 0.75, P = 0.273). Age, excision amount, use of postsurgical drains, and BMI were not associated with increased complications (P = 0.29, P = 0.55, P = 0.74, P = 0.41). Rates of areolar sensation loss were higher in larger BMIs, but this was not statistically significant (P = 0.051).

Conclusions:

The MPWP reduction technique is an equally safe and effective treatment of gigantomastia when compared with reduction with free nipple graft reconstruction. There is the added benefit of preserved nipple sensation without increased postoperative complications.
Microsurgical Needle Retention Does Not Cause Pain or Neurovascular Injury in a Rat Model
Authors: Arora Jagmeet S. , Kim Joshua K. , Pakvasa Mikhail , Sayadi Lohrasb R. , Lem Melinda , Widgerow Alan D. , Leis Amber R.
Published: August 2023

Background:

Approximately 20% of retained foreign bodies are surgical needles. Retained macro-needles may become symptomatic, but the effect of microsurgical needles is uncertain. We present the first animal model to simulate microsurgical needle retention. Given a lack of reported adverse outcomes associated with macro-needles and a smaller cutting area of microsurgical needles, we hypothesized that microsurgical needles in rats would not cause changes in health or neurovascular compromise.

Methods:

Male Sprague-Dawley rats (x̄ weight: 288.9 g) were implanted with a single, 9.0 needle (n = 8) or 8.0 needle (n = 8) orthogonal to the right femoral vessels and sutured in place. A control group (n = 8) underwent sham surgery. Weekly, a cumulative health score evaluating body weight, body condition score, physical appearance, and behavior for each rat was determined. Infrared thermography (°C, FLIR one) of each hindlimb and the difference was obtained on postoperative days 15, 30, 60, and 90. On day 90, animals were euthanatized, hindlimbs were imaged via fluoroscopy, and needles were explanted.

Results:

The mean, cumulative health score for all cohorts at each weekly timepoint was 0. The mean temperature difference was not significantly different on postoperative days 15 (P = 0.54), 30 (P = 0.97), 60 (P = 0.29), or 90 (P = 0.09). In seven of eight rats, 8.0 needles were recovered and visualized on fluoroscopy. In six of eight rats, 9.0 needles were recovered, but 0/8 needles were visualized on fluoroscopy.

Conclusions:

Microsurgical needle retention near neurovascular structures may be benign, and imaging for needles smaller than 8.0 may be futile. Further studies should explore microsurgical needle retention potentially through larger animal models.
The outcomes and prognostic factors of patients with hepatocellular carcinoma and Child-Turcotte-Pugh class B
Authors: Fu Chia-Chu , Chen Yu-Jen , Su Chien-Wei , Wei Cheng-Yi , Chu Chi-Jen , Lee Pei-Chang , Huo Teh-Ia , Huang Yi-Hsiang , Huang Hui-Chun , Wu Jaw-Ching , Hou Ming-Chih
Published: August 2023

Background:

The Child-Turcotte-Pugh (CTP) score is widely used for assessing the liver’s functional reserve in patients with advanced chronic liver disease (ACLD) and hepatocellular carcinoma (HCC). This study aims to explore the outcomes of patients with HCC and CTP class B and to investigate the prognostic accuracy of prediction models for ACLD in these patients.

Methods:

We retrospectively enrolled 1143 patients with HCC and CTP class B between 2007 and 2022. We divided the patients into three subgroups based on their CTP scores: CTP-B7, CTP-B8, and CTP-B9. We compared the corrected Akaike information criterion among each mortality prediction model, including the CTP score, albumin-bilirubin (ALBI) score, modified ALBI score, the model for end-stage liver disease (MELD), and MELD 3.0.

Results:

Among the enrolled patients, 576 (50.3%) were in the CTP-B7 group, 363 (31.8%) were in the CTP-B8 group, and 204 (17.9%) were in the CTP-B9 group. After a median follow-up of 4.6 months (interquartile range IQR 1.8–17.2 months), 963 patients died, and the 5-year overall survival (OS) rate was 11.4%. The 5-year OS rates were 11.6%, 13.6%, and 8.3% in the CTP-B7, CTP-B8, and CTP-B9 groups, respectively. Patients in the CTP-B7 group and CTP-B8 group had comparable OS (p = 0.089), both of which were better than those in the CTP-B9 group (p < 0.001). Furthermore, the MELD 3.0 score had the lowest corrected akaike information criteria value and provided a more accurate mortality prediction than the MELD score, ALBI grade, modified ALBI grade, and CTP score.

Conclusion:

Patients in the CTP-B7 and CTP-B8 groups had comparable OS, both of which were better than those in the CTP-B9 group. Moreover, MELD 3.0 provided the most accurate mortality prediction in patients with HCC and CTP class B.
Prevalence of Sonographic Achilles Tendon, Patellar Tendon, and Plantar Fascia Abnormalities in Division I Collegiate Athletes From a Variety of Sports
Authors: Cushman Daniel M. , Carefoot Andrea , Corcoran Blake , Vu Leyen , Fredericson Michael , Fausett Cameron , Teramoto Masaru , Eby Sarah F.
Published: August 2023

Objective:

This study aimed to determine the prevalence of ultrasound abnormalities in the Achilles tendon, patellar tendon, and plantar fascia among a large cohort of collegiate student-athletes.

Design:

Observational cross-sectional study.

Setting:

Three Division I institutions.

Participants:

243 student-athletes participated in this study. Exclusion criteria included those younger than 18 years or who underwent prior surgery/amputation of structures, including anterior cruciate ligament (ACL) surgeries with patellar tendon grafts.

Interventions:

Ultrasound examination of the Achilles tendon, patellar tendon, and plantar fascia of each leg was performed. An experienced sonographer reviewed each tendon video in a blinded manner, with a separate experienced sonographer separately reviewing to establish inter-rater reliability.

Main Outcome Measures:

The primary outcome measured was the presence of any sonographic abnormality including hypoechogenicity, thickening, or neovascularity.

Results:

Ultrasound abnormalities were identified in 10.1%, 37.2%, and 3.9% of all Achilles tendons, patellar tendons, and plantar fasciae, respectively. Abnormalities were significantly associated with the presence of concurrent pain for all structures (P < 0.01). Specifically, athletes with sonographic abnormalities were approximately 4 times [relative risk (RR) = 4.25; 95% confidence interval (CI), 2.05-8.84], 6 times (RR = 5.69; 95% CI, 2.31-14.00), and 5 times (RR = 5.17; 95% CI, 1.76-15.25) more likely to self-report pain in the Achilles tendon, patellar tendon, and plantar fascia, respectively.

Conclusions:

This multi-institutional study completed at 3 Division I institutions is the largest study of its kind to identify the prevalence of sonographic abnormalities in the Achilles tendon, patellar tendon, and plantar fascia among collegiate student-athletes of various sports.
Effectiveness of an Occupational Well-being Intervention Among Nurse Educators
Authors: Rinne Jenni , Leino-Kilpi Helena , Saaranen Terhi , Tarvainen Mika P. , Pasanen Miko , Koskinen Sanna , Salminen Leena
Published: August 2023

Background:

Occupational well-being supports the retention of the nurse educator workforce and their ability to manage workload. There is a research gap regarding interventions promoting occupational well-being.

Purpose:

To evaluate the effectiveness of an 8-workweek digital occupational well-being intervention using self-conducted exercises among nurse educators in secondary vocational nursing schools in Finland.

Methods:

A quasi-experimental study design was applied using an intervention group (n = 37) and a control group (n = 40). Data were collected at baseline, post, and 1-month follow-up using a questionnaire and a heart rate sensor to assess the resource-workload-balance and its associating and promoting factors.

Results:

This study found no statistical effects on the resource-workload-balance. Positive effects were found on associating factors (general well-being) and promoting factors (recovery experiences and self-regulation).

Conclusions:

Self-Help INtervention for Educators (SHINE) has the potential to promote recovery experiences during working hours; however, the intervention needs more investigation.
The Impact of Noise on Nursing Preceptors’ Assessment of Student Performance
Authors: Najm Danielle , Whittall Dawn , Pillay Kamini , Morphet Julia
Published: August 2023

Background:

Noise is a relatively new concept highlighting the variability of cognitive inputs people grapple with when making a judgment. In this case, preceptors make a judgment of students’ clinical performance during clinical practicum. There is scant literature examining the impact of noise on nursing student assessment.

Purpose:

This article explores the noise that influences nursing preceptors’ assessment of students in clinical practice.

Method:

A qualitative descriptive design was used, and interviews were conducted with preceptors from the clinical setting.

Results:

Three themes were identified, describing the tensions faced by preceptors when assessing students and the noise that impacted those assessments.

Conclusion:

Both system noise and individual noise impacted the process and outcome of nursing student assessment during clinical practicum.
Malnutrition and Nutrition Support in Latin American PICUs: The Nutrition in PICU (NutriPIC) Study
Authors: Campos-Miño Santiago , Figueiredo-Delgado Artur , Zárate Patricia , Zamberlan Patricia , Muñoz-Benavides Eliana , Coss-Bu Jorge A. ,   on behalf of the Nutrition Committee, Latin American Society of Pediatric Intensive Care (SLACIP)
Published: August 2023

OBJECTIVES:

To characterize the nutritional status of children admitted to Latin American (LA) PICUs and to describe the adequacy of nutrition support in reference to contemporary international recommendations.

DESIGN:

The Nutrition in PICU (NutriPIC) study was a combined point-prevalence study of malnutrition carried out on 1 day in 2021 (Monday 8 November) and a retrospective cohort study of adequacy of nutritional support in the week preceding.

SETTING:

Four-one PICUs in 13 LA countries.

PATIENTS:

Patients already admitted to the PICU of 1 month to 18 years old on the study day were included in the point-prevalence study. For the retrospective arm, we included patients receiving nutritional support on the study day and with a PICU length of stay (LOS) greater than or equal to 72 hours. Exclusion criteria were being a neonate, conditions that precluded accurate anthropometric measurements, and PICU LOS greater than 14 days.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Of 316 patients screened, 5 did not meet age criteria. There were 191 of 311 patients who were included in the point-prevalence study and underwent anthropometric evaluation. Underweight and length for age less than –2 z scores were present in 42 of 88 children (47.7%) and 41 of 88 children (46.6%) less than 24 months old, and 14 of 103 (13.6%) and (23/103) 22.3% of 103 children greater than or equal to 24 months, respectively. Evidence of obesity (body mass index > 2 z score) was present in 7 of 88 children (5.7%) less than 24 months old and 13 of 103 children (12.6%) greater than or equal to 24 months. In the 115 of 311 patients meeting criteria for the retrospective arm, a total of 98 patients reported complete nutritional data. The 7-day median (interquartile range) adequacy for delivered versus recommended enteral energy and protein requirement was 114% (75, 154) and 99% (60, 133), respectively.

CONCLUSIONS:

The NutriPIC study found that in 2021 malnutrition was highly prevalent especially in PICU admissions of less than 24 months old. Retrospectively, the 7-day median nutritional support appears to meet both energy and protein requirements.
The Effect of Botulinum Toxin A on the NADPH Oxidase System and Ischemia-Reperfusion Injury
Authors: Kyung Hyun Woo , Lee Seokui , Kwon Hyeokjae , Kim Sunje , Kim Joo Hak , Song Seung Han , Oh Sang-Ha , Yang Ho Jik , Ha Yooseok
Published: August 2023

Background:

Despite the increasing popularity of various materials for ischemia-reperfusion (I/R) injury mitigation, research on botulinum toxin type A (BoNTA) remains limited. This study assesses BoNTA’s efficacy in protecting flaps from I/R injury by inhibiting the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system and reducing reactive oxygen species (ROS) production.

Methods:

Seventy-six Sprague-Dawley rats were studied. We examined the effects of BoNTA on superoxide production in four rats using a lucigenin-enhanced chemiluminescence assay (LECL). Another group of 60 rats had their superficial inferior epigastric artery (SIEA) flaps treated with either BoNTA or saline and clamped for 0, 1, and 4 hours before reperfusion. Flap survival and histological outcomes were assessed five days post-operation. ROS production in SIEA flaps and femoral vessels was analyzed in 12 additional rats, post-I/R injury.

Results:

The LECL results showed that the BoNTA group had significantly lower superoxide production compared to controls, with notable reductions at 4 hours. While no significant differences were noted at the 0 and 1-hour marks, the 4-hour mark showed significant protective effects in BoNTA-treated groups. The survival rate was 90% for BoNTA-treated rats versus 60% for controls (P = 0.028). Significant reductions in ROS were also observed in the 4-hour I/R group.

Conclusions:

BoNTA effectively protects against I/R injury by inhibiting the NADPH oxidase system and reducing ROS levels. These results support further investigation into the specific mechanisms of NADPH oxidase inhibition by BoNTA and its potential clinical applications, given its safety profile

Clinical Relevance Statement:

The findings from the present study are expected to provide a basis for clinical studies regarding this use of BoNTA.
Congenital Epulis: A Rare Head And Neck Tumor in the Newborn
Authors: De Stefano Sofia , Nadal López Emmanuela , Sabas Mariana
Published: August 2023

Congenital epulis is a rare tumor; when voluminous and ulcerated, appearance can generate concern. Nevertheless, it is a benign lesion that is easily treated with surgery.

This is a retrospective study, with the presentation of 2 cases treated by the same team from 2016 to 2020 and a bibliographic review (PubMed and Elsiever). This surgical team is based in Buenos Aires, working in the private medical system.

Congenital epulis is an infrequent, benign tumor affecting females predominantly, appearing at birth on the alveolar median ridge of the maxilla. Its pathogenesis is uncertain. Voluminous tumors interfere with feeding, but respiratory interference is exceptional. Histologically, this tumor is similar to the granular cell tumor but has different clinical characteristics and Periodic Acid Schiff stain. Ecographic or magnetic resonance imaging prenatal diagnosis is ideal if undiagnosed prenatally. Clinical diagnosis is done based on typical features. Surgical excision is the treatment of choice.
Relationship of Sleep Health and Endoscopic Disease Activity in Inflammatory Bowel Disease
Authors: Kamp Kendra J. , Yoo Linda , Clark-Snustad Kindra , Winders Samantha , Burr Robert , Buchanan Diana , Barahimi Mitra , Jacobs Jeffrey , Heitkemper Margaret , Lee Scott D.
Published: August 2023

Among adults with inflammatory bowel disease (IBD), self-reported sleep disturbances are associated with active symptoms, but the association between sleep measures and endoscopic disease activity is unknown. This study aimed to (1) compare sleep–wake behaviors among IBD patients based on endoscopic and clinical disease activity and (2) describe associations between actigraphy, self-reported sleep measures, and symptoms of fatigue, anxiety, and depression. Participants wore a wrist actigraph for 10 consecutive days and completed self-reported sleep questionnaires (Pittsburgh Sleep Quality Index [PSQI] and Patient-Reported Outcome Measures System [PROMIS] Sleep Disturbance and Sleep Interference questionnaires). Clinical and endoscopic disease activity were assessed. Based on actigraphic recordings (n = 26), average total nighttime sleep was 437 minutes and sleep efficiency was 84%. Objective sleep measures did not differ based on endoscopic or clinical disease activity. Individuals with active clinical disease had higher PROMIS Sleep Disturbance (57.3 vs. 49.7, d = 1.28) and PROMIS Sleep-Related Impairment (58.1 vs. 52.8, d = 0.51) compared with those with inactive clinical disease. Self-reported sleep was significantly associated with anxiety, depression, and fatigue. Further research is needed to better characterize the relationship between sleep and endoscopic disease activity, and determine underlying mechanisms related to poor sleep in the IBD population.
Metschnikowia ahupensis f.a., sp. nov., a new yeast species isolated from the gut of the wood-feeding termite Nasutitermes sp.
Authors: Tiwari Snigdha , Lee Dong Kyung , Lachance Marc-André , Baghela Abhishek
Published: August 2023

The gut of xylophagous insects such as termites harbours various symbiotic micro-organisms, including many yeast species. In a taxonomic study of gut-associated yeasts, two strains (ATS2.16 and ATS2.18) were isolated from the gut of the wood-feeding termite Nasutitermes sp. in Maharashtra, India. Morphological and physiological characteristics and sequence analyses of the ITS and D1/D2 region of the large subunit rRNA gene revealed that these two strains represent a novel asexual ascomycetous yeast species in the genus Metschnikowia. The species differs from some of its close affiliates in the genus in its inability to utilize ethanol and succinate as the sole carbon source and growth in high sugar concentrations (up to 50 % glucose). In contrast to most members of Metschnikowia, the formation of ascospores was not observed on various sporulation media. Moreover, whole-genome sequencing was used to further confirm the novelty of this species. When compared with other large-spored Metschnikowia species, average nucleotide identity values of 79–80 % and digital DNA–DNA hybridization values of 16–17 % were obtained. The name Metschnikowia ahupensis f.a., sp. nov. is proposed to accommodate this novel yeast species, with ATS2.16 as the holotype and strains NFCCI 4949, MTCC 13085 and PYCC 9152 as isotypes. The MycoBank number is MB 844210.
Evolutionary genomics identifies host-directed therapeutics to treat intracellular bacterial infections
Authors: Medicielo Josette , Waltari Eric , Glascock Abigail Leigh , Dudas Gytis , DeFelice Brian , Gray Ira , Tato Cristina M. , Wong Joan , Ahyong Vida
Published: August 2023

Obligate intracellular bacteria shed essential biosynthetic pathways during their evolution towards host dependency, providing an opportunity for host-directed therapeutics. UsingRickettsiaceaeas a model, we employed a novel computational pipeline called PoMeLo to systematically compare this cytosolic family of bacteria to the relatedAnaplasmataceae, which reside in a membrane-bound vacuole in the host cell. We identified 20 metabolic pathways that have been lost since the divergence ofAnaplasmataceaeandRickettsiaceae, corresponding to the latter’s change to a cytosolic niche. We hypothesized that drug inhibition of these host metabolic pathways would reduce the levels of metabolites available to the bacteria, thereby inhibiting bacterial growth. We tested 22 commercially available inhibitors for 14 of the identified pathways and found that the majority (59%) reduced bacterial growth at concentrations that did not induce host cell cytotoxicity. Of these, 5 inhibitors with an IC50under 5 μM were tested to determine whether their mode of inhibition was bactericidal or bacteriostatic. Both mycophenolate mofetil, an inhibitor of inosine-5’-monophosphate dehydrogenase in the purine biosynthesis pathway, and roseoflavin, an analog of riboflavin, displayed bactericidal activity. A complementary unbiased mass spectrometry-based metabolomics approach identified 14 pathways impacted byRickettsiainfection based on alterations in metabolite levels. Strikingly, 11 of these (79%) overlapped with those identified by our computational predictions. Thesein vitrovalidation studies support the feasibility of a novel evolutionary genomics-guided approach for host-directed antibiotic drug development against obligate pathogens.

Importance

Many pathogens have evolved to acquire essential metabolites from their host cell, while in turn shedding their own biosynthetic capacities. This leads to an interesting dilemma: on one hand, reduced genomes allow pathogens to save energy and replicate more quickly, while on the other hand, they become more dependent on the host cell for survival. This vulnerability can be exploited by identifying and therapeutically inhibiting the host pathways that are essential for pathogen survival. The significance of our research is in predicting the precise pathways lost during a pathogen’s evolutionary adaptation to parasitism and validating these predictions through targetedin vitrogrowth assays and an unbiased metabolomic survey of the host-pathogen interface.
Chaperone Complexes From The Endoplasmic Reticulum (ER) And The Cytosol Inhibit wt-p53 By Activation The ER To Cytosol Signaling
Authors: Dabsan Salam , Zur Gali , Gilad Ayelet , Igbaria Aeid
Published: August 2023

The Endoplasmic Reticulum (ER) is an essential sensing organelle responsible for the folding and secretion of almost one-third of eukaryotic cells’ total proteins. The ER contains numerous enzymes and chaperones which assist in oxidative protein folding and other posttranslational modifications. However, environmental, chemical, and genetic insults often lead to protein misfolding in the ER, accumulating misfolded proteins, altering homeostasis, and causing ER stress. Recently, we reported a novel ER surveillance mechanism by which proteins from the secretory pathway are refluxed to the cytosol to relieve the ER of its content during stress. In cancer cells, the refluxed proteins gain new pro-survival functions, thereby increasing cancer cell fitness. We termed this phenomenonERtoCYtosolSignaling (or “ERCY”). In yeast, ERCYS is regulated by HLJ1 (an ER-resident tail-anchored HSP40 cochaperone). Here, we found that in mammalian cells, HLJ1 has five putative orthologs possessing J-domains facing the cytosol. Among those, DNAJB12 and DNAJB14 appear to be the most significant. Mechanistically, we found that DNAJB12 and DNAJB14 bind the cytosolic HSC70 and its cochaperone – SGTA - through their cytosolically localized J-domains to facilitate ER-protein reflux to the cytosol. Moreover, we found that DNAJB12 is necessary and sufficient to drive this phenomenon to increase AGR2 reflux and inhibit wt-p53 during ER stress. Thus, we concluded that targeting the DNAJB12/14-HSC70/SGTA axis is a promising strategy to inhibit ERCYS and impair cancer cell fitness.
Combined kinome inhibition states are predictive of cancer cell line sensitivity to kinase inhibitor combination therapies
Authors: Joisa Chinmaya U. , Chen Kevin A. , Beville Samantha , Stuhlmiller Timothy , Berginski Matthew E. , Okumu Denis , Golitz Brian T. , Johnson Gary L. , Gomez Shawn M.
Published: August 2023

Protein kinases are a primary focus in targeted therapy development for cancer, owing to their role as regulators in nearly all areas of cell life. Kinase inhibitors are one of the fastest growing drug classes in oncology, but resistance acquisition to kinase-targeting monotherapies is inevitable due to the dynamic and interconnected nature of the kinome in response to perturbation. Recent strategies targeting the kinome with combination therapies have shown promise, such as the approval of Trametinib and Dabrafenib in advanced melanoma, but similar empirical combination design for less characterized pathways remains a challenge. Computational combination screening is an attractive alternative, allowing in-silico screening prior to in-vitro or in-vivo testing of drastically fewer leads, increasing efficiency and effectiveness of drug development pipelines. In this work, we generate combined kinome inhibition states of 40,000 kinase inhibitor combinations from kinobeads-based kinome profiling across 64 doses. We then integrated these with baseline transcriptomics from CCLE to build robust machine learning models to predict cell line sensitivity from NCI-ALMANAC across nine cancer types, with model accuracy R2∼ 0.75-0.9 after feature selection using elastic-net regression. We further validated the model’s ability to extend to real-world examples by using the best-performing breast cancer model to generate predictions for kinase inhibitor combination sensitivity and synergy in a PDX-derived TNBC cell line and saw reasonable global accuracy in our experimental validation (R2∼ 0.7) as well as high accuracy in predicting synergy using four popular metrics (R2∼ 0.9). Additionally, the model was able to predict a highly synergistic combination of Trametinib (MEK inhibitor) and Omipalisib (PI3K inhibitor) for TNBC treatment, which incidentally was recently in phase I clinical trials for TNBC. Our choice of tree-based models over networks for greater interpretability also allowed us to further interrogate which specific kinases were highly predictive of cell sensitivity in each cancer type, and we saw confirmatory strong predictive power in the inhibition of MAPK, CDK, and STK kinases. Overall, these results suggest that kinome inhibition states of kinase inhibitor combinations are strongly predictive of cell line responses and have great potential for integration into computational drug screening pipelines. This approach may facilitate the identification of effective kinase inhibitor combinations and accelerate the development of novel cancer therapies, ultimately improving patient outcomes.
REPRODUCTIVE COMPATIBILITY OF TWO LINES OFDELIA PLATURA(DIPTERA: ANTHOMYIIDAE)
Authors: Bush-Beaupré Allen , Bélisle Marc , Fortier Anne-Marie , Fournier François , MacDonald Andrew , Savage Jade
Published: August 2023

Accurate identification of agricultural pests is a major component of integrated pest management. The seedcorn maggot,Delia platura(Diptera: Anthomyiidae), is a cosmopolitan polyphagous pest species which may be found in high numbers in numerous crops. Two morphologically identical genetic lines ofD. platura(H- and N- lines) with distinct distributions were recently identified. However, no study to date has investigated the reproductive compatibility of the two lines and thus the possibility that they may actually be two unique biological entities. A previous study described the reproductive traits of the two lines and suggested that H-line females are highly selective towards the male with which they mate, pointing to a possible pre-mating isolation mechanism between the lines. Using laboratory-reared colonies originating from the Montérégie region in Québec, this study investigates the reproductive compatibility of the twoD. platuralines. We found that only one of thirty H-line females was inseminated by an N-line male, further suggesting mate choice as a pre-mating isolation mechanism between the lines. However, N-line females were readily inseminated by H-line males, suggesting a lack of pre-mating isolation in this type of cross. The eggs laid by N-line females mated with H-line males had a lower hatching rate than the ones laid by females of intra-line crosses suggesting either post-mating pre-zygotic or post-zygotic partial isolation. However, the larvae that did hatch had a comparable developmental success to those from intra-line crosses in terms of survival and developmental time from larval hatching to adult emergence, pupal weight, and adult sex ratio, suggesting a lack of post-zygotic isolation for these life stages. Considering the different biological traits of the two lines, we suggest the use of the ‘biotype’ terminology to designate the two biological entities and discuss their implications for integrated pest management.
Spatio-temporal patterns of whiting (Merlangius merlangus) in the Adriatic Sea under environmental forcing
Authors: Asciutto Emanuele , Maioli Federico , Manfredi Chiara , Anibaldi Alessandra , Cimini Jacopo , Isailović Igor , Marčeta Bojan , Casini Michele
Published: August 2023

Understanding how environmental factors affect species distribution is crucial for the conservation and management of marine organisms, especially in the face of global changes. Whiting (Merlangius merlangus) is a demersal temperate fish, considered a ‘relict species’ in the Adriatic Sea. Despite its significance to commercial fisheries in the region, the specific drivers behind its spatial and temporal patterns have not been thoroughly examined. Here, we fitted a set of Generalized Linear Mixed Effects Models to data collected in the Northern and Central Adriatic from 1999 to 2019 during the Mediterranean International Trawl Survey to investigate the potential influence of depth, seafloor temperature and bottom dissolved oxygen on the annual biomass density and spatial distribution of whiting. Our results showed that depth, and to a lesser degree temperature and oxygen, are important predictors of whiting distribution in spring-summer, with preferences for depths of ∼ 45 m, temperature of ∼ 15.4 °C and dissolved oxygen > 5.5 ml L-1. We predicted a persistent core area of distribution in front of the Po River Delta, in the Northern Adriatic Sea, while the density progressively declined towards the Central and Southern Adriatic Sea along the Italian coast. Additionally, the temporal trend exhibited high fluctuations over the years, occurring in cycles of 3 to 4 years. Finally, by comparing the biomass density estimates obtained under optimum conditions with those derived from the actual values for each variable, our analysis revealed that temperature had a pronounced and general impact on biomass density in the northern survey area (prediction revealed a ratio of density reduction of approximatively a half), while oxygen displayed a minor and more localized influence. This work deepens the current knowledge about the ecology of whiting in the Adriatic Sea and provides support for the conservation and management of this species.
Discretised flux balance analysis for reaction-diffusion simulation of single-cell metabolism
Authors: Chew Yin Hoon , Spill Fabian
Published: August 2023

Metabolites have to diffuse within the sub-cellular compartments they occupy to specific locations where enzymes are, so reactions could occur. Conventional flux balance analysis (FBA), a method based on linear programming that is commonly used to model metabolism, implicitly assumes that all enzymatic reactions are not diffusion-limited though that may not always be the case. In this work, we have developed a spatial method that implements FBA on a grid-based system, to enable the exploration of diffusion effects on metabolism. Specifically, the method discretises a living cell into a two-dimensional grid, represents the metabolic reactions in each grid element as well as the diffusion of metabolites to and from neighbouring elements, and simulates the system as a single linear programming problem. We varied the number of rows and columns in the grid to simulate different cell shapes, and the method was able to capture diffusion effects at different shapes. We then used the method to simulate heterogeneous enzyme distribution, which suggested a theoretical effect on variability at the population level. We propose the use of this method, and its future extensions, to explore how spatiotemporal organisation of sub-cellular compartments and the molecules within could affect cell behaviour.