bluuebunny/crossref_metadata_2025 huggingface dataset:
A pathway independent multi-modular ordered control system based on thermosensors and CRISPRi improves bioproduction in Bacillus subtilis
Authors: Yu Wenwen , Jin Ke , Wu Yaokang , Zhang Quanwei , Liu Yanfeng , Li Jianghua , Du Guocheng , Chen Jian , Lv Xueqin , Ledesma-Amaro Rodrigo , Liu Long
Published: June 2022

Dynamic regulation is an effective strategy for control of gene expression in microbial cell factories. In some pathway contexts, several metabolic modules must be controlled in a time dependent or ordered manner to maximize production, while the creation of genetic circuits with ordered regulation capacity still remains a great challenge. In this work, we develop a pathway independent and programmable system that enables multi-modular ordered control of metabolism in Bacillus subtilis. First, a series of thermosensors were created and engineered to expand their thresholds. Then we designed single-input-multi-output circuits for ordered control based on the use of thermosensors with different transition points. Meanwhile, a repression circuit was constructed by combining CRISPRi-based NOT gates. As a proof-of-concept, these genetic circuits were applied for multi-modular ordered control of 2′-fucosyllactose (2′-FL) biosynthesis, resulting in a production of 1839.7 mg/l in shake flask, which is 5.16-times that of the parental strain. In a 5-l bioreactor, the 2′-FL titer reached 28.2 g/l with down-regulation of autolysis. Taken together, this work provides programmable and versatile thermosensitive genetic toolkits for dynamic regulation in B. subtilis and a multi-modular ordered control framework that can be used to improve metabolic modules in other chassis cells and for other compounds.
Patterns of care in adult histone mutant gliomas: Results of an international survey
Authors: Yuile Alexander , Khasraw Mustafa , Low Justin T , Walsh Kyle M , Lipp Eric , Sy Joanne , Satgunaseelan Laveniya , Kastelan Marina Ann , De Silva Madhawa , Lee Adrian , Wheeler Helen
Published: June 2022

Background

Histone mutant gliomas (HMG) with histone H3 K27 and G34 mutations are recognized as biologically discrete entities with distinct anatomical locations, younger age at presentation (in comparison to the most common high-grade gliomas, IDH wildtype glioblastoma), and poor prognosis. There is a paucity of data regarding the management of adult HMG patients and no consensus on management. This study aims to identify current patterns of Australian and US neuro-oncology clinical practice for this entity.

Methods

Following institutional approvals, patterns of care questionnaire designed to capture relevant clinical variables was circulated through the Cooperative Trials Group for Neuro-Oncology (COGNO) in Australia and the Caris Precision Oncology Alliance in the United States (US).

Results

Between 4/2021 and 10/2021, 43 responses were collected. 33% (n = 14) of responders tested all patients for HMGs routinely; 40.92% (n = 18) tested in select patients 26% (n = 11) did not test for HMGs. The common indications for testing selected patients were midline anatomic location (n = 18) and age (n = 11) (<50 years). 23 used molecular sequencing, 22 used IHC at their centers. Nine participants stated knowledge of histone H3 mutations did not affect their management of these gliomas, 11 said it affected their management at the time of recurrence, 23 stated it affected the management of midline K27M patients, 11 participants stated it affected the management of K27M mutant gliomas in other locations, and 3 felt it affected the management of G34R/V mutant gliomas.

Conclusion

Here we present a description of how the discovery of a new molecular subtype of primary glial tumors, histone mutated gliomas in adults, is being introduced into clinical practice.
Diagnostic challenges of radiological opacities in silicosis - case reports
Authors: Smărăndescu R A , Căluțu I M , Rașcu A , Bușnatu Ș S
Published: June 2022

Occupational exposure to crystalline silica dust in the workplace can cause lung damage (silicosis, chronic airflow limitation and lung cancer). Silicosis results from the fibrotic reaction to the deposition of inhaled crystalline silica dust in the lung tissue. Even though many coalmines and foundries have closed, crystalline silica is still widely used, making silicosis a significant public health issue. Occupational exposure to crystalline silica must be considered when diagnosing respiratory symptoms to avoid under- or misdiagnosis. The diagnosis of silicosis relies on acknowledging the causal relationship linked to exposure, the pulmonary radiological changes and the exclusion of other diseases with imaging or clinical characteristics similar to silicosis. The diagnosis is often not straightforward and, in many cases, histopathological examination is necessary for confirmation. In this case report, we present two cases in which an initial misdiagnosis led to inadequate treatment.
Cortisol awakening response in the airborne rescue service
Authors: Braun D , Frank M , Theiler L , Petrowski K
Published: June 2022

Background

Work-related stress may lead to mental and physical illnesses. Emergency physicians may be particularly vulnerable to developing such diseases due to their extreme emotional working environment.

Aims

The purpose of the study was to analyse the hormonal stress burden of emergency physicians in the airborne rescue service to create an empirical basis for developing appropriate measures against chronic stress in the rescue service.

Methods

Three salivary cortisol samples were collected after awakening in 15 min intervals—each on a flight rescue day, a clinic day and a free day—to calculate the extent of the hormonal stress load of the emergency physicians. A nested linear mixed-model analysis was used in 40 cases to investigate hormonal stress. Furthermore, professional years and gender were included in the calculations.

Results

The mixed model showed neither a main effect for measurement time nor for day but a significant interaction effect (P = 0.002). The cortisol level rises strongly on the flight rescue and the clinic day, while on the free day it shows a moderate increase. Professional years and gender also proved to be statistically significant for the cortisol level of emergency physicians (P < 0.001).

Conclusions

The results show a significantly higher cortisol increase on working days compared with a free day, which indicates a stronger stress burden on working days of emergency physicians in the airborne rescue service. Future studies should examine the stress level of emergency physicians in more detail to prove whether the working conditions of emergency physicians need to be modified.
In-Hospital Mortality Among Hospitalized Coronavirus Disease 2019 Patients in the United States: How Did It Change in 2021?
Authors: Moon Rena C , Rosenthal Ning A
Published: June 2022

In this retrospective observational study in a US national sample of 501 671 adults hospitalized with coronavirus disease 2019, adjusted in-hospital mortality decreased from 12% in February 2021 to 9% in April 2021. However, adjusted in-hospital mortality increased to 16% in September and October 2021. Adjusted intensive care unit admission fluctuated between 20% and 27% in 2021.
Real-world Experience of Sotrovimab in High-risk, Immunocompromised COVID-19 Patients
Authors: Birk Navina K , Jain Saniya , Massoud Louis , Ramesh Diya , Monday Lea , Muma Bruce , Williams Jonathan , Alangaden George , Ramesh Mayur
Published: June 2022

We completed a real-world analysis of 498 consecutive high-risk nonimmunocompromised and immunocompromised patients who received sotrovimab during the B.1.1.529 surge. Emergency department visits/hospitalizations and 30-day all-cause mortality between the 2 groups were similar. When administered early, sotrovimab is effective at preventing coronavirus disease 2019 progression in immunocompromised and nonimmunocompromised patients.
In vivo diagnostics of abiotic plant stress responses via in situ real-time fluorescence imaging
Authors: Fu Yi-Xuan , Liu Shi-Yu , Guo Wu-Yingzheng , Dong Jin , Nan Jia-Xu , Lin Hong-Yan , Mei Long-Can , Yang Wen-Chao , Yang Guang-Fu
Published: June 2022

A hydroxyphenylpyruvate dioxygenase-targeted fluorescent biosensor enables the early diagnostics of abiotic stresses in plants.
The mediating role of work–family conflicts in the association between work ability and depression among Egyptian civil workers
Authors: Abdelrehim M G , Eshak E S , Kamal N N
Published: June 2022

Background

Work ability and work–family conflicts (total-WFCs) were associated with the risk of depression among the working population.

Methods

We recruited 3104 Egyptian civil workers between October 2019 and January 2020. The Work Ability Index (WAI), Center for Epidemiologic Studies-Depression (CES-D) and Midlife Development in the United States questionnaires were used to collect the data. Following Baron and Kenny criteria, the mediation effect of total-WFCs on the association between WAI and CES-D scores was tested by multivariable linear regression models.

Results

Findings revealed a high prevalence of depressive symptoms (CES-D score ≥ 16) among Egyptian civil servants (43.4%). There were negative relationships between WAI score and both CES-D score (B = −0.70, P < 0.001) and total-WFCs score (B = −0.22, P < 0.001). Moreover, WAI score was still significantly associated with CES-D score after controlling for total-WFCs score (B = −0.40, P < 0.001) that suggests partial mediation. We estimated that ~44%, 38% and 20% of the total effect of work ability on the risk of depressive symptoms were mediated by total-WFCs, family-to-work conflict and work-to-family conflict, respectively.

Conclusions

Interventions aiming for mitigation total-WFCs can help improve employees’ mental health and reduce the risk of impaired work ability-related depression.
Neural Correlates of Variation in Personal Space and Social Functioning in Schizophrenia and Healthy Individuals
Authors: Zapetis Sarah L , Nasiriavanaki Zahra , Luther Lauren , Holt Daphne J
Published: June 2022

Background

Changes in the regulation of interpersonal distance, or “personal space” (PS), have been repeatedly observed in schizophrenia and, in some studies, linked to negative symptoms. However, the neurobiological basis of these impairments is poorly understood.

Methods

Personal space measurements, functional connectivity of a brain network sensitive to intrusions into PS, and symptoms of social withdrawal and anhedonia were assessed, and associations among these outcomes measured, in 33 individuals with a psychotic disorder (primarily schizophrenia [SCZ]) and 36 control subjects (CON).

Results

Personal space size was significantly higher (P = .002) and PS permeability (reflecting the capacity to tolerate intrusions into PS) was significantly lower (P = .021) in the SCZ relative to the CON group, and both measures were significantly correlated with social anhedonia and withdrawal in the full sample (all P < .007). Moreover, functional connectivity between the PS and default mode (DM) networks was significantly correlated with the permeability, but not the size, of PS in the full sample and in the SCZ and CON groups separately, and with social withdrawal in the SCZ group. Lastly, the association between PS-DM network connectivity and social withdrawal in the SCZ group was fully mediated by PS permeability.

Discussion

Neural and behavioral aspects of PS regulation are linked to social motivation in both healthy individuals and those with psychotic disorders, suggesting that measurements of PS could serve as transdiagnostic markers of social functioning.
Environmental performance of commercial beef production systems utilizing conventional productivity-enhancing technologies
Authors: Aboagye Isaac A , Cordeiro Marcos R C , McAllister Tim A , May Matt L , Hannon Sherry J , Booker Calvin W , Parr Sandi L , Schunicht Oliver C , Burciaga-Robles Luis O , Grimson Tracey M , Boonstra Emily , Mengistu Genet F , Fulawka Deanne L , Ominski Kim H
Published: June 2022

The objective of this study was to evaluate the effects of using conventional productivity-enhancing technologies (PETs) with or without other natural PETs on the growth performance, carcass traits, and environmental impacts of feedlot cattle. A total of 768 cross-bred yearling steers (499 ± 28.6 kg; n = 384) and heifers (390 ± 34.9 kg; n = 384) were offered a barley grain-based basal diet and divided into implanted or non-implanted groups. Steers were then allocated to diets that contained either: (i) no additive (control); natural feed additives including (ii) fibrolytic enzymes (Enz), (iii) essential oil (Oleo), (iv) direct-fed microbial (DFM), (v) DFM + Enz + Oleo combination; conventional feed additives including (vi) Conv (monensin, tylosin, and beta-adrenergic agonists [βAA]); or Conv with natural feed additives including (vii) Conv + DFM + Enz; (viii) Conv + DFM + Enz + Oleo. Heifers received one of the first three dietary treatments or the following: (iv) probiotic (Citr); (v) Oleo + Citr; (vi) Melengesterol acetate (MGA) + Oleo + βAA; (vii) Conv (monensin, tylosin, βAA, and MGA); or (viii) Conv + Oleo (ConvOleo). Data were used to estimate greenhouse gas (GHG) and ammonia (NH3) emissions, as well as land and water use. Implant and Conv-treated cattle exhibited improvements in growth and carcass traits as compared to the other treatments (P < 0.05). Improvements in the performance of Conv-cattle illustrated that replacing conventional feed additives with natural feed additives would increase both the land and water required to satisfy the feed demand of steers and heifers by 7.9% and 10.5%, respectively. Further, GHG emission intensity for steers and heifers increased by 5.8% and 6.7%, and NH3 emission intensity by 4.3% and 6.7%, respectively. Eliminating the use of implants in cattle increased both land and water use by 14.6% and 19.5%, GHG emission intensity by 10.5% and 15.8%, and NH3 emission intensity by 3.4% and 11.0% for heifers and steers, respectively. These results demonstrate that the use of conventional PETs increases animal performance while reducing the environmental impacts of beef production. Restricting use would increase the environmental footprint of beef produced for both domestic and international markets.
Interaction of urea with frequency and amount of distillers grains supplementation for growing steers on a high forage diet
Authors: Linder Haley F , Sebade Josh E , Carlson Zac E , Wilson Hannah C , Spore Tyler J , Drewnoski Mary E , MacDonald Jim C
Published: June 2022

Two studies were conducted to determine interactions of urea inclusion to a dried distillers grains plus solubles (DDGS; 29.4% crude protein, 5.48% ether extract) supplement fed at two amounts and two frequencies to steers on a high forage diet. In Exp. 1, 120 (247 kg; SD = 20) steers were fed individually for 84 d. Steers received ad libitum grass hay (6.8% crude protein) and one of eight treatments. Treatment design was a 2 × 2 × 2 factorial. Supplement was fed daily or three times per week, amount of supplement fed was 6.36 kg dry matter (DM)/week [0.37% body weight (BW); LO] or 12.73 kg DM/week (0.74% BW; HI) and contained either no urea or 1.3% urea on a DM basis. Steer BW was measured at the start and end of the trial and hay DM intake (DMI) was measured weekly. In Exp. 2, ruminally cannulated steers (310 kg; SD = 25) were used in a row-column design with eight steers and six 14-d periods. Treatments assigned were the same as Exp. 1, except that supplement was fed at 0.4% of BW (LO) or 0.8% of BW (HI) and supplement was fed either daily (DY) or every other day (ALT). Hay DMI, rumen ammonia-N, rumen pH, in situ neutral detergent fiber (NDF) disappearance, and rumination were measured. In Exp. 1, average daily gain (ADG) was affected by amount of supplement with steers on HI gaining 0.30 kg/d more (P < 0.01) than LO. Hay DMI was reduced by increased amount of supplement (0.39 kg/d; P < 0.01) and by decreased frequency of supplementation (0.54 kg/d; P < 0.01). In Exp. 2, hay DMI was also reduced due to increased amount of supplement and decreased frequency of supplementation (P < 0.01). Rumen pH was decreased on the day of supplement feeding for steers on ALT (P < 0.01) and reduced for steers fed HI vs. LO. There was no difference in NDF digestibility between DY and ALT (P > 0.05). For ALT steers, there was reduction (P < 0.01) in in situ NDF disappearance for the HI compared to LO amount of supplementation on the day of supplementation. Infrequent supplementation of DDGS results in no difference in ADG but decreased hay DMI compared to daily supplementation. Urea had no effect on digestion or ADG, suggesting rumen degradable protein was not deficient when supplementing DDGS. There is little change in rumen fermentation parameters between frequency of supplement feeding, indicating that forage digestion is not impacted by supplementation frequency. Dried distillers grains can be supplemented infrequently without a reduction in animal performance.
Healthcare Compensation Plans: Current Challenges and Novel Approaches
Authors: Zigrang Todd A.
Published: June 2022

The US healthcare sector differs from others, particularly with regard to how its workforce is compensated. In healthcare's third-party payer system, the consumer (i.e., the patient) typically is not the one paying for the service. Moreover, the payment for a given service is negotiated by the provider and the third-party payer before the patient ever seeks care—and the payment for the same service may differ among payers and patients. To further complicate matters, myriad overlapping federal, state, and local statutes and regulations govern how providers interact with patients and each other. The challenges with compensating physicians have been amplified by the healthcare workforce shortage that was looming even before the onset of the COVID-19 pandemic. In light of these various forces in the healthcare industry, this article reviews the current ways healthcare providers are compensated and the challenges with those compensation plans. Potential approaches to remedy those challenges are described, both broadly and with specific real-world examples related to primary care and surgical specialties. Lessons learned from these approaches include ways that healthcare organizations may measure the success of a compensation plan.
A Novel Murine Model of Endothelial Keratoplasty
Authors: Nakagawa Hayate , Blanco Tomas , Kahale Francesca , Wang Shudan , Musayeva Aytan , Alemi Hamid , Dohlman Thomas H. , Dana Reza
Published: June 2022

Purpose:

The purpose of this study was to establish a murine model of endothelial keratoplasty.

Methods:

Endothelial keratoplasty (EK) was performed using C57BL/6 donor and BALB/c recipient mice. The central endothelium and Descemet membrane were removed from the recipient cornea, and a 1.5-mm posterior lamellar donor graft was made adherent to the recipient cornea with a small amount of viscoelastic. Mice were followed through slitlamp microscopy postoperatively, and OCT was used to assess the cornea and anterior chamber and measure central corneal thickness. Histology and immunohistochemistry were performed to confirm graft adherence and endothelial cell morphology.

Results:

Successfully attached EK grafts were visualized in all transplanted animals. Histology and immunostaining confirmed proper graft orientation and adherence, as well as the presence of donor endothelium on transplanted grafts. We observed maximal corneal edema in all animals at day 1 postoperatively which gradually subsided. EK graft survival was 97% at 8 weeks.

Conclusions:

In this study, we describe a novel murine model for EK which we anticipate will enable detailed investigation into the cellular and molecular mechanisms involved in EK pathobiology.
Mismatched Unrelated Donor Hematopoietic Stem Cell Transplantation Rescues Marrow Failure From Acute Leukemia Therapy in a Patient With Previously Undiagnosed Ligase IV Syndrome
Authors: Fridlyand Diana M. , Chandrakasan Shanmuganathan , Aljudi Ahmed , Aumann Waitman K. , Westfall Eleanor , Kirwan Bailey , Bryson Elyse W. , Keller Frank G. , Arnold Staci D. , Hong Andrew L. , Pauly Melinda , Williams Kirsten M.
Published: June 2022

Patients with DNA double-strand breakage repair disorders are at increased risk of malignancy which is often difficult to treat given underlying sensitivity to chemotherapy and radiotherapy, lending an important role to hematopoietic stem cell transplantation. The choice of conditioning regimen used must balance reducing risk of rejection with minimizing excessive toxicity from myeloablative chemotherapy or ionizing radiation. We describe successful engraftment following a nonmyeloablative hematopoietic stem cell transplantation in a patient with Ligase IV syndrome and numerous pretransplant complications including malignancy, cardiac failure, and secondary hemophagocytic lymphohistiocytosis. Congruent with prior reports, a reduced intensity regimen appears efficacious in Ligase IV syndrome patients.
The Clinical Landscape of NRAS-mutated Juvenile Myelomonocytic Leukemia-like Myeloproliferation Includes Children With Costello Syndrome
Authors: Pabari Reena , Chun Kathy , Naqvi Ahmed
Published: June 2022

Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive pediatric disorder characterized by pathologic myeloproliferation because of alterations in RAS pathway genes. NRAS-mutated JMML encompasses a broad range of clinical severity. Herein we describe 4 unique cases of NRAS-mutated JMML and JMML-like myeloproliferation, 2 with somatic mutations and 2 with germline mutations. These cases illustrate the diverse clinical and hematologic presentation of this subtype of JMML, including a very unusual example presenting with Auer rods. Lastly, this is the first report of patients with phenotypic Costello syndrome presenting with JMML-like myeloproliferation, highlighting an important clinical phenomenon that has not been previously described.
Symptom Duration and Diabetic Control Influence Success of Steroid Injection in Trigger Finger
Authors: Hollins Andrew W. , Hein Rachel , Atia Andrew , Taskindoust Mahsa , Darner Grant , Shammas Ronnie , Mithani Suhail K.
Published: June 2022

Background:

Trigger finger is one of the most common hand abnormalities, with a prevalence of 2 percent of the general population. Conservative treatment with corticosteroid injections at the A1 pulley has been shown to be a cost-effective first-line treatment. However, additional patient factors have not fully been described regarding steroid injection efficacy. The authors hypothesize that patients presenting with longer chronicity of symptoms before treatment and elevated blood glucose would have reduced success rates of steroid injection therapy.

Methods:

A retrospective chart review of 297 patients at a single institution was performed between 2013 and 2019. Patients were included if they presented with the diagnosis of trigger finger and were treated with initial corticosteroid injection at the A1 pulley.

Results:

Steroid injection therapy alone was successful in 65 percent of patients. Patients received on average of 1.61 steroid injections. Patients who failed treatment received an average of 1.85 injections compared to 1.49 for those who had successful corticosteroid injection therapy (p = 0.001). Presence of ipsilateral hand disease was associated with significant increase in failure of steroid injections (43.4 percent versus 30.8 percent; p = 0.032). Diabetic patients with hemoglobin A1c levels greater than 6.5 percent had a significantly higher rate of failing steroid injection therapy (71.9 percent versus 38.1 percent; p < 0.001). Patients who presented with greater than 2.5 months of symptoms had a higher failure rate of corticosteroid therapy (40.4 percent versus 29.5 percent; p = 0.048).

Conclusion:

Patients with a coexisting diagnosis of diabetes and a hemoglobin A1c level greater than 6.5 percent, ipsilateral concomitant hand disease, or presence of symptoms for greater than 2.5 months should be counseled regarding higher risk of failure of local corticosteroid injection.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Ten Years of Posterior Cranial Vault Expansion by Means of Distraction Osteogenesis: An Update and Critical Evaluation
Authors: Humphries Laura S. , Zapatero Zachary D. , Vu Giap H. , Hoppe Ian , Swanson Jordan W. , Bartlett Scott P. , Taylor Jesse A.
Published: June 2022

Background:

The goal of this study was to describe the 10-year evolution of the authors’ surgical technique and institutional perioperative outcomes using posterior vault distraction osteogenesis (PVDO) in patients with syndromic and multisuture craniosynostosis.

Methods:

The authors performed a retrospective cohort study of patients who underwent PVDO for treatment of syndromic and multisuture craniosynostosis at a single institution over a 10-year period. Demographic data, perioperative outcomes, distraction patterns, and complications were analyzed. Outcomes of patients in the first 5 years (early cohort) were compared with those of the latter 5 years (late cohort).

Results:

One hundred ten patients underwent a total of 118 PVDO procedures. Patients with a syndromic diagnosis represented 83.6 percent of the cohort (n = 92) and were significantly younger than patients with a nonsyndromic diagnosis at the time of first PVDO (median [25th percentile, 75th percentile] 14.1 [6.6, 40.1] versus 42.7 [15.2, 59.6] months; p = 0.014). Mean distraction distance in the anterior–posterior direction was 30.8 mm (SD, 7.4). Compared with the early cohort, PVDO in the late cohort had faster median operative times (144.0 [123.0, 189.0] minutes versus 161.0 [138.0, 199.0] minutes; p = 0.038), lower estimated blood loss as a percentage of blood volume (28.5 [20.6, 45.3] versus 50.0 [31.1, 95.8]; p < 0.001), and lower blood replacement as percentage of blood volume (39.5 [23.8, 59.1] versus 56.3 [37.8, 110.1]; p = 0.009).

Conclusions:

This 10-year experience with PVDO demonstrates continued overall safety and efficacy with improved perioperative outcomes over time. Although PVDO has become the authors’ first line of expansion in syndromic craniosynostosis, shortcomings such as need for device removal, infection concerns, and potential for cerebrospinal fluid leak merit attention by the craniofacial community.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
A qualitative study on stakeholder perceptions of digital prosthetic socket fabrication for transtibial amputations
Authors: Mayo Amanda L. , Gould Sarah , Cimino Stephanie R. , Glasford Shane , Harvey Evan , Ratto Matt , Hitzig Sander L.
Published: June 2022

Background:

Digital residual limb shape capture (three-dimensional [3D] scanning), computer-assisted design (CAD), and computer-assisted manufacturing with 3D printing technology show promise for a completely digital process of fabricating prosthetic sockets for patients with limb loss. The effectiveness and quality of digitally designed 3D-printed lower extremity prosthetic sockets is understudied, and there is lack of data on the patient and prosthetist experiences with this digital workflow.

Objective:

To obtain stakeholder feedback on the feasibility and acceptability of using a completely digital prosthetic fabrication process consisting of 3D scanning, CAD, and 3D printing in a rehabilitation setting for adults with transtibial limb amputations.

Study design:

Qualitative design.

Methods:

Study participants with a transtibial-level amputation were fit with a prosthetic socket fabricated using digital shape capture with a 3D scanner, CAD, and 3D printing in addition to a traditionally handcasted manually fabricated socket. Participants tried on and evaluated both sockets. Semistructured interviews took place after the fitting appointments. A focus group was conducted with prosthetists to obtain their feedback. Audio data were transcribed verbatim, and an inductive content analysis was undertaken.

Results:

Eleven patient participants and 3 prosthetists identified 4 main themes: 1) openness and enthusiasm for digital prosthetic fabrication; 2) relative advantages of digital fabrication vs. traditional socket fabrication; 3) readiness of the technology used for adoption in practice; and 4) digital prosthetic workflow and 3D printing implementation considerations.

Conclusions:

Patients and prosthetists were enthusiastic about digital prosthetic socket fabrication and saw potential advantages over traditional methods. Both patients and prosthetists had concerns about the durability, safety, and aesthetics of the 3D printed sockets in this study. Further studies are needed to optimize digital prosthetic fabrication with 3D printing in prosthetic practice.
Does thermoplastics' thickness influence joint stabilization and movement coordination? An inferential study of wrist orthoses
Authors: de Almeida Pedro H T Q , Santos Bruno Batista , Bernardo Lilian Dias , MacDermid Joy C
Published: June 2022

Background:

Given the existence of multiple low-temperature thermoplastics, clinicians fabricating can readily modify an orthoses' thickness, weight and flexibility, among other properties. However, there is limited evidence on the impact of such different materials on upper extremities' biomechanics.

Objective:

Our study aimed to investigate differences in joint stabilization and movement coordination provided by upper extremity orthotics fabricated with low-temperature thermoplastics of different thicknesses.

Study Design:

Inferential, cross-sectional study

Method:

We conducted a kinematic analysis of a standardized task through a three-dimensional motion capture system. Ten participants (5 female) performed the same task under three circumstances: 1) wearing a volar wrist immobilization orthosis, made with a 3.2-mm thick low-temperature thermoplastic; 2) using the same orthotic fabricated with a 1.6-mm thick material; and (3) without orthoses. We divided the standardized task into five logical phases for data analysis, obtaining the active range of motion of the shoulder, elbow, forearm, and wrist joints as the primary outcome. Secondary outcomes included movement smoothness and coordination, measured by the number of motor units, time, and distance travelled by the upper extremity.

Results:

Despite changes in thermoplastic thickness, both orthotics significantly restricted the wrist motion during task performance (F(2,16) = 14.32, P < .01, and η2
p = 0.797), with no difference between the 2 devices and no significant changes to proximal joints' active range of motion. Although orthoses use increased the time required for task performance (F(2,16) = 23.05, P < .01, and η2
p = 0.742), no significant differences in movement smoothness or coordination were noted.

Conclusion:

Our results indicate that wrist orthoses fabricated with a 1.6-mm thick low-temperature thermoplastic can provide joint stabilization similar to a device made from a 3.2-mm thickness material, suggesting thinner thermoplastics' efficacy to stabilize joints in the absence of contractures or preexisting chronic conditions.
Late (≥5 y) Complications of Laparoscopic Vertical Sleeve Gastrectomy (LVSG) and Laparoscopic Roux-en-Y Gastric Bypass (LRYGB): A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Osland Emma J. , Yunus Rossita M. , Khan Shahjahan , Memon Muhammed A.
Published: June 2022

Background:

There is a paucity of data that compares the relative complication profiles of laparoscopic vertical sleeve gastrectomy (LVSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) at 5 years.

Objectives:

The aim was to compare late complications of LVSG and LRYGB.

Methods:

We updated our previous systematic review and meta-analysis of randomized controlled trials of primary LVSG and LRYGB procedures in adults, to review late (5 years) complication outcomes (PROSPERO 112054). Electronic databases were searched from January 2015 to July 2021 for publications meeting inclusion criteria. The Hartung-Knapp-Sidik-Jonkman random effects model was utilized to estimate weighted mean differences where meta-analysis was possible. Bias and certainty of evidence was assessed using the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluations.

Results:

Four randomized controlled trials met the inclusion criteria (n=531; LVSG=272, LRYGB=259). No late treatment-related mortality was reported with either procedure. A significant reduction in surgical reoperations (odds ratio: 0.47, 95% confidence interval: 0.27-0.82, P=0.01) and endoscopic interventions (odds ratio: 0.29, 95% confidence interval: 0.12-0.71, P=0.02) were reported at 5 years post-LVSG relative to LRYGB. Reoperations were more frequently performed for reflux management in LVSG and for internal hernia repairs in LRYGB. Complications requiring medical management were common following both procedures. Limitations included few eligible studies for inclusion, and varying definitions of medically managed complications.

Conclusions:

LRYGB is associated with a higher proportion of surgical and endoscopic interventions at 5 years compared with LVSG. More high-quality, long-term studies are required to further elucidate both surgical and nutritional long-term outcomes post these procedures.
Changes in Polypharmacy and Psychotropic Medication Use After Diagnosis of Major Neurocognitive Disorders
Authors: Maltais Annie , Simard Marc , Vedel Isabelle , Sirois Caroline
Published: June 2022

Background:

Older adults with major neurocognitive disorder (MNCD) are often exposed to polypharmacy. We aimed to assess the prescribing and discontinuation patterns of medications following diagnosis of MNCD among community-dwelling older adults.

Methods:

Using the Quebec Integrated Chronic Disease Surveillance System, we conducted a population-based cohort study comparing 1-year prediagnosis and postdiagnosis use of medications between a group of individuals older than 65 years newly diagnosed with MNCD in 2016-2017 and a control group without MNCD. The difference-in-difference method was used to estimate the prediagnosis and postdiagnosis variation in the number of medications prescribed and in the proportion of psychotropic and anticholinergic medication users.

Results:

In the MNCD group, the mean number of medications used (excluding Alzheimer disease treatments) increased by 1.25 in the year after the diagnosis. The respective increase was 0.45 in the control group, yielding an adjusted difference-in-differences of 0.81 (95% confidence interval: 0.74; 0.87) between groups. The adjusted difference-in-differences in the proportions of antipsychotic, antidepressant, and anticholinergic medication users was 13.2% (12.5; 13.9), 7.1% (6.5; 7.7), and 3.8% (3.1; 4.6), respectively.

Conclusions:

The medication burden among older adults tends to increase in the year following a diagnosis of MNCD. The use of antipsychotics and antidepressants may explain a part of the observed increase.
Disinfection methods of dental unit waterlines contamination: a systematic review
Authors: Wu Mengting , Shi Zhiwei , Yu Xuefen , Xu Yuedan , Jin Xinyang , Zhang Ling , Fu Baiping
Published: June 2022

Background. Severe contamination of dental unit waterlines was found in healthcare settings. The benefits of decontamination methods are controversial. The aim of this review was to systematically evaluate disinfection methods in contamination control of dental unit waterlines.

Methods. The terms ‘dental unit waterline(s) or DUWL(s) or dental unit water line(s)’ were searched through PubMed, Cochrane Library, Embase, Web of Science and Scopusup to 31 May 2021. The DUWLs’ output water was incubated on R2A agar at 20–28 °C for 5–7 days to evaluate heterotrophic mesophilic bacteria. The risk of bias was evaluated by a modified Newcastle-Ottawa quality assessment scale.

Results. Eighteen papers from the literature were included. One study indicated that water supply played a crucial role in disinfecting DUWLs. Three studies indicated that flushing decreased bacteria counts but did not meet the American CDC standard (500 c.f.u. ml−1). All chlorine- and peroxide-containing disinfectants except sodium hypochlorite in one of 15 studies as well as three mouthrinses and citrus botanical extract achieved the standard (≤500 c.f.u. ml−1). The included studies were of low (1/18), moderate (6/18) and high (11/18) quality.

Conclusion. Independent water reservoirs are recommended for disinfecting DUWLs using distilled water. Flushing DUWLs should be combined with disinfections. Nearly all the chlorine-, chlorhexidine- and peroxide-containing disinfectants, mouthrinses and citrus botanical extract meet the standard for disinfecting DUWLs. Alkaline peroxide would lead to tube blockage in the DUWLs. Regularly changing disinfectants can reduce the risk of occurrence of disinfectant-resistant strains of microbes.
Force propagation between epithelial cells depends on active coupling and mechano-structural polarization
Authors: Ruppel Artur , Wörthmüller Dennis , Misiak Vladimir , Kelkar Manasi , Wang Irène , Moreau Philippe , Méry Adrien , Révilloud Jean , Charras Guillaume , Cappello Giovanni , Boudou Thomas , Schwarz Ulrich S. , Balland Martial
Published: June 2022

Cell-generated forces play a major role in coordinating the large-scale behavior of cell assemblies, in particular during development, wound healing and cancer. Mechanical signals propagate faster than biochemical signals, but can have similar effects, especially in epithelial tissues with strong cell-cell adhesion. However, a quantitative description of the transmission chain from force generation in a sender cell, force propagation across cell-cell boundaries, and the concomitant response of receiver cells is missing. For a quantitative analysis of this important situation, here we propose a minimal model system of two epithelial cells on an H-pattern (“cell doublet”). After optogenetically activating RhoA, a major regulator of cell contractility, in the sender cell, we measure the mechanical response of the receiver cell by traction force and monolayer stress microscopies. In general, we find that the receiver cells shows an active response so that the cell doublet forms a coherent unit. However, force propagation and response of the receiver cell also strongly depends on the mechano-structural polarization in the cell assembly, which is controlled by cell-matrix adhesion to the adhesive micropattern. We find that the response of the receiver cell is stronger when the mechano-structural polarization axis is oriented perpendicular to the direction of force propagation, reminiscent of the Poisson effect in passive materials. We finally show that the same effects are at work in small tissues. Our work demonstrates that cellular organization and active mechanical response of a tissue is key to maintain signal strength and leads to the emergence of elasticity, which means that signals are not dissipated like in a viscous system, but can propagate over large distances.
Normative values of neuromelanin-sensitive MRI signal in older adults obtained using a standard protocol for acquisition and analysis
Authors: Al Haddad Rami , Chamoun Mira , Tardif Christine L , Guimond Synthia , Horga Guillermo , Rosa-Neto Pedro , Cassidy Clifford M
Published: June 2022

Background

The integrity and function of catecholamine neurotransmitter systems can be assessed using MRI sequences often referred to as neuromelanin-sensitive MRI (NM-MRI). The relevance of this method to neurodegenerative and psychiatric disorders is becoming increasingly evident, and it has potential as a clinical biomarker. To support such future applications, we report here the normative range of NM-MRI signal and volume metrics in cognitively normal older adults.

Methods

3 Tesla NM-MRI images and demographic and cognitive data were available from 152 cognitively normal older adults aged 53-86 years old at baseline; a subsample of 68 participants also had follow-up NM-MRI data collected around one-year later. NM-MRI images were processed to yield summary measures of volume and signal (contrast-to-noise ratio, CNR) for the substantia nigra (SN) and locus coeruleus (LC) using a recently developed software employing a fully automated algorithm. The extent of annual change in these metrics was quantified and tested for significance using 1-sample t-tests.

Results

Baseline SN signal (CNR) was 10.02% (left SN) and 10.28% (right) and baseline LC signal was 24.71% (left) and 20.42% (right). The only NM-MRI metric to show a significant annual change was a decrease in left SN volume.

Conclusion

We report normative values for NM-MRI signal and volume in the SN and LC of cognitively normal older adults and normative values for their change over time. These values may help future efforts to use NM-MRI as a clinical biomarker for adults in this age range by facilitating identification of patients with extreme NM-MRI values.
Transmembrane proteins tetraspanin 4 and CD9 sense membrane curvature
Authors: Dharan Raviv , Goren Shahar , Cheppali Sudheer Kumar , Shendrik Petr , Brand Guy , Yu Li , Kozlov Michael M. , Sorkin Raya
Published: June 2022

Multiple membrane shaping and remodelling processes are associated with tetraspanin proteins by yet unknown mechanisms. Tetraspanins constitute a family of proteins with four transmembrane domains present in high copy numbers in every cell type. Prominent examples are tetraspanin4 and CD9 that are required for the fundamental cellular processes of migrasome formation and fertilization, respectively. These proteins are enriched in curved membrane structures, such as cellular retraction fibers and oocyte microvilli. The factors driving this enrichment are, however, unknown. Here we revealed that tetrasapnin4 and CD9 are curvature sensors with a preference for positive membrane curvature. To this end we used a biomimetic system emulating membranes of cell retraction fibers and oocyte microvilli by membrane tubes pulled out of giant plasma membrane vesicles with controllable membrane tension and curvature. We developed a simple thermodynamic model for the partitioning of curvature sensors between flat and tubular membranes, which allowed us to estimate the individual intrinsic curvatures of the two proteins. Overall, our findings illuminate the process of migrasome formation and oocyte microvilli shaping and provide insight into the role of tetraspanin proteins in membrane remodelling processes.
Hippocampal microstructural and neurobehavioral differences in welders are related to higher R2* in the red nucleus
Authors: Lee Eun-Young , Kim Juhee , Prado-Rico Janina Manzieri , Du Guangwei , Lewis Mechelle M. , Kong Lan , Yanosky Jeff D. , Kim Byoung-Gwon , Hong Young-Seoub , Mailman Richard B. , Huang Xuemei
Published: June 2022

Introduction

Metal exposure has been associated with higher risk of neurodegenerative disorders such as Alzheimer’s disease (AD). We examined the potential link between welding-related metal co-exposure (e.g., Fe, Mn, Pb) and AD-related structural and neurobehavioral metrics.

Methods

Subjects with (welders; n=42) or without (controls; n=31) a history of welding were examined. Metal exposure was estimated by exposure questionnaires and whole blood metal levels. Brain metal accumulations were estimated by MRI R1 (Mn) and R2* (Fe) in the caudate, putamen, globus pallidus, red nucleus (RN), and hippocampus. AD-related structural differences were assessed by volume and diffusion tensor imaging metrics in the hippocampus, and neurobehavioral aspects by learning/memory task scores.

Results

Compared to controls, welders displayed higher blood metal levels (p’s <0.004) and R2* values in the caudate and RN (p’s<0.024). Caudate R2* values were associated with blood Fe (p=0.043), whereas RN R2* values were correlated with blood Pb (p=0.003). Welders had higher hippocampal mean diffusivity (MD; p=0.011) and lower Story Recall scores (p=0.049), but no difference in volume or domain-wise learning/memory performance (p’s>0.117). Group differences in hippocampal MD and Story Recall scores were greater with higher RN R2* values (p’s<0.016). Moreover, RN R2* values reflected an indirect link between blood Pb and hippocampal MD (p=0.036) across both groups.

Discussion

Welders had hippocampal structural and learning/memory performance differences similar to those in AD-at-risk populations. These AD-like differences in welders may, in part, be linked to Pb exposure reflected by higher RN R2* levels at the brain level.
Modeling cellular co-infection and reassortment of bluetongue virus in Culicoides midges
Authors: Cavany Sean M. , Barbera Carly , Carpenter Molly , Rodgers Case , Stenglein Mark , Mayo Christie , Perkins T. Alex
Published: June 2022

When related segmented RNA viruses co-infect a single cell, viral reassortment can occur, potentially leading to new strains with pandemic potential. One virus capable of reassortment is bluetongue virus, which causes substantial health impacts in ruminants and is transmitted via Culicoides midges. Because midges can become co-infected by feeding on multiple different host species and remain infected for their entire life-span, there is high potential for reassortment to occur. Once a midge is co-infected, additional barriers must be crossed for a reassortant virus to emerge, such as cellular co-infection and dissemination of reassortant viruses to the salivary glands. We developed three mathematical models of within-midge bluetongue virus dynamics of increasing complexity, allowing us to explore the conditions leading to the emergence of reassortment viruses. In confronting the simplest model with published data, we estimate the average lifespan of a bluetongue virion in the midge midgut is about six hours, a key determinant of establishing a successful infection. Examination of the full model, which permits cellular co-infection and reassortment, shows that small differences in fitness of the two infecting strains may have a large impact on the frequency with which reassortant virions are observed. This is consistent with experimental co-infection studies with BTV strains with different relative fitnesses that did not produce reassortant progeny. Our models also highlight several gaps in existing data which would allow us to elucidate these dynamics in more detail, in particular the times it takes the virus to disseminate to different tissues, and measurements of viral load and reassortant frequency at different temperatures.
Antimicrobial peptides can generate tolerance by lag and interfere with antimicrobial therapy
Authors: Sandín García Daniel , Valle Javier , Morata Jordi , Andreu David , Burgas Marc Torrent
Published: June 2022

Antimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can generate tolerance as an intermediate stage towards resistance is not known. Here we show that treatment of Escherichia coli with different AMPs induces tolerance by lag, particularly for those peptides that have internal targets. This tolerance can be detected as different morphological and physiological changes, which depend on the type of peptide molecule the bacterium has been exposed to. In addition, we show that AMP tolerance can also affect antibiotic treatment. Genomic sequencing of AMP-tolerant strains shows that different mutations alter membrane composition, DNA replication, and translation. Some of these mutations have also been observed in antibiotic-resistant strains, suggesting that AMP tolerance could be a relevant step in the development of antibiotic resistance. Monitoring AMP tolerance is relevant with a view to eventual therapeutic use of AMPs and because cross-tolerance might favor the emergence of resistance against conventional antibiotic treatments.