bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Paraspinal Muscle Volume on Physiological Load on the Lumbar Vertebral Column
Authors: Kang Sungwook , Chang Min Cheol , Kim Hwanjin , Kim Jaewoong , Jang Youngjae , Park Donghwi , Hwang Jong-moon
Published: March 2021

Study Design.

Analytical biomechanical study using a finite-element (FE) model.

Objective.

We investigated the effects of paraspinal muscle volume to the physiological loading on the lower lumbar vertebral column using a FE model.

Summary of Background Data.

The FE model analysis can measure the physiological load on the lumbar vertebral column. Which changes as the surrounding environment changes. In this study, our FE model consisted of the sacrum, lumbar spine (L3–L5), intervertebral discs, facet joints, and paraspinal muscles.

Methods.

Three-dimensional FE models of healthy lumbar spinal units were reconstructed. The physiological loads exerted on the lumbar vertebra column were evaluated by applying different paraspinal muscle volumes (without muscles, 50%, 80%, and 100% of healthy muscle volume).

Results.

As the paraspinal muscle volume increased, the loads exerted on the vertebral column decreased. The mean load on the intervertebral disc was 1.42 ± 0.75 MPa in the model without muscle, 1.393 ± 0.73 MPa in the 50% muscle volume model, 1.367 ± 0.71 MPa in the 80% muscle volume model, and 1.362 ± 0.71 MPa in the 100% muscle volume model. The mean loads exerted on the posterior column of lumbar spine were 11.79 ± 4.70 MPa in the model without muscles, 11.57 ± 4.57 MPa in the model with 50% muscle volume, and 11.13 ± 4.51 MPa in the model with 80% muscle volume, and 10.92 ± 4.33 MPa in the model with 100% muscle volume. The mean pressure on the vertebral body in the model without paraspinal muscle, and with 50%, 80%, and 100% paraspinal muscle volume were 14.02 ± 2.82, 13.82 ± 2.62, 13.65 ± 2.61, and 13.59 ± 2.51 MPa, respectively.

Conclusion.

Using FEM, we observed that the paraspinal muscle volume decreases pressure exerted on the lumbar vertebral column. Based on these results, we believe that exercising to increase paraspinal muscle volume would be helpful for spinal pain management and preventing lumbar spine degeneration.

Level of Evidence: N/A
Comparison of Cost and Perioperative Outcome Profiles for Primary and Revision Posterior Cervical Fusion Procedures
Authors: Martini Michael L. , Baron Rebecca B. , Gal Jonathan S. , Neifert Sean N. , Shuman William H. , Schupper Alexander J. , Chapman Emily K. , McNeill Ian T. , Steinberger Jeremy , Caridi John M.
Published: March 2021

Study Design.

Retrospective analysis.

Objective.

To compare perioperative outcomes and hospitalization costs between patients undergoing primary or revision posterior cervical discectomy and fusion (PCDF).

Summary of Background Data.

While prior studies found differences in outcomes between primary and revision anterior cervical discectomy and fusion (ACDF), risk, and outcome profiles for posterior cervical revision procedures have not yet been elucidated.

Methods.

Institutional records were queried for cases involving isolated PCDF procedures to evaluate preoperative characteristics and outcomes for patients undergoing primary versus revision PCDF between 2008 and 2016. The primary outcome was perioperative complications, while perioperative and resource utilization measures such as hospitalization length, required stay in the intensive care unit (ICU), direct hospitalization costs, and 30-day emergency department (ED) admissions were explored as secondary outcomes.

Results.

One thousand one hundred twenty four patients underwent PCDF, with 218 (19.4%) undergoing a revision procedure. Patients undergoing revision procedures were younger (53.0 vs. 60.5 yrs), but had higher Elixhauser scores compared with the non-revision cohort. Revision cases tended to involve fewer spinal segments (3.6 vs. 4.1 segments) and shorter surgical durations (179.3 vs. 206.3 min), without significant differences in estimated blood loss. There were no significant differences in the overall complication rates (P = 0.20), however, the primary cohort had greater rates of required ICU stays (P = 0.0005) and non-home discharges (P = 0.0003). The revision cohort did experience significantly increased odds of 30-day ED admission (P = 0.04) and had higher direct hospitalization (P = 0.03) and surgical (P < 0.0001) costs.

Conclusion.

Complication rates, including incidental durotomy, were similar between primary and revision PCDF cohorts. Although prior surgery status did not predict complication risk, comorbidity burden did. Nevertheless, patients undergoing revision procedures had decreased risk of required ICU stay but greater risk of 30-day ED admission and higher direct hospitalization and surgical costs.

Level of Evidence: 3
In Quest of Tablet Apps for Elders With Alzheimer's Disease
Authors: Tak Sunghee H.
Published: March 2021

Caregivers search for mobile device apps that offer meaningful and enjoyable activities to simultaneously enhance the preserved cognitive and functional abilities of those in their care. The purpose of this review article was to describe the current state of tablet apps with which elders with Alzheimer's disease and related forms of dementia may engage as users. Using the keywords “app,” “Alzheimer's,” and “dementia,” a sample of 83 apps was selected from the iTunes Store, Google, and discussion boards of Apple Support Communities. A descriptive content analysis was conducted using a coding scheme on the characteristics of tablet app activity and the requirements for functional abilities of the users. This review found that the activities of the selected apps included games, simple watching and viewing, music and sounds, memory training, learning and information, and social interaction starters. A high-level cognitive and physical ability such as eye-hand coordination is often required to play the majority of the game apps. A few apps are designed specifically for the population. Individuals' variability in cognitive and functional abilities necessitates a person-centered approach in designing and selecting games and activities for apps in order to increase engagement and promote positive experiences in older adults.
An Evaluation of Opioid Use in Black Communities: A Rapid Review of the Literature
Authors: Jordan Ayana , Mathis Myra , Haeny Angela , Funaro Melissa , Paltin Dafna , Ransome Yusuf
Published: March 2021

Background

There are multiple aspects of the opioid crisis among Black people, who have been left out of the broader conversation. Despite evidence of increased opioid overdose deaths, less is known about opioid use among Black people. This review synthesizes research on Black people who use opioids; the goals are to advance knowledge, highlight research gaps, and inform clinical practice.

Methods

This rapid review investigating opioid use among Black people utilized systematic review methods and was conducted according to a predefined protocol with clear inclusion criteria (PROSPERO ID: 177071). A comprehensive search strategy was used, including published and gray-literature sources (i.e., literature that has not been formally published). A narrative summary of the results is presented.

Results

A total of 76 works were selected for inclusion and full text review. Sex, age, geographic location, and involvement in the carceral system were associated with the use of opioids among Black individuals. Non-epidemiologic factors included treatment-seeking patterns, disparate clinician prescribing, and social determinants.

Conclusions

Through this rapid review we suggest three main areas of focus: (1) including culturally informed collection methods in epidemiologic surveys to accurately reflect prevalences, (2) funding research that specifically addresses the importance of culture in accessing treatment, and (3) directly studying how social determinants can improve or exacerbate health outcomes. Focusing on the unique needs of Black people who use opioids is warranted to increase treatment initiation and adherence among a population less likely to engage with the traditional health care system.
Kingella kingae
Authors: Almeida Borges Madalena , Silva Sara , Ferreira Raquel , Martins Catarina , Paixão Paulo , Rodrigues Vitória , Farela Neves João
Published: March 2021

Kingella kingae is the leading cause of osteoarticular infections between 6 and 48 months, a well-known cause of pediatric bacteremia and endocarditis and has been rarely associated with meningitis. We report a case of a healthy 10-year-old boy with meningitis due to Kingella kingae who presented with a history of severe headache, vomiting and prostration.
Human milk proteome: what's new?
Authors: Dingess Kelly A. , Li Cheng , Zhu Jing
Published: March 2021

Purpose of review

The proteome is one of the most complicated and multifunctional components in human milk. Recently, numerous novel characteristics of the human milk proteome have been discovered, which are described and critically examined in this review.

Recent findings

Recent human milk proteomics studies have focused on how external factors like geography and environment, or maternal and infant's factors affect the milk proteins, endogenous peptides, their posttransitional modifications (PTMs) and infant utilization. Most of these studies have shown that major protein and endogenous peptide profiles are similar for healthy women and infants. The human milk proteome has been expanded by providing novel insights into PTMs like glycosylation and phosphorylation, and how the proteins and peptides are digested and utilized by the infant. All human milk proteomics studies are subject to conditions in which the samples were collected, handled and stored.

Significant technological advancements in mass spectrometry have considerably enabled a deeper and more comprehensive identification and characterization of the expanded human milk proteome. However, data concerning human milk from mothers with infections or illnesses and mothers nursing more vulnerable infants are still limited and the roles of the components of the human milk proteome have not yet been sufficiently elucidated.
Analysis of the F-18 FDG PET/CT features of pulmonary sclerosing pneumocytoma
Authors: Liu Honghong , Dang Haodan , Wang Ruimin , Yao Shulin , Wu Yue , Xu Baixuan
Published: March 2021

Purpose

This retrospective study aimed to analyzed the F-18 fluorodeoxyglucose PET/computed tomography (F-18 FDG PET/CT) features of pulmonary sclerosing pneumocytoma (PSP) to improve the understanding and preoperative diagnostic efficacy of this rare disorder.

Methods

FDG PET/CT images from 11 patients with 22 lesions (including one patient with 12 lesions) proven PSP in our hospital were reviewed. We summarized the PET/CT features of PSP and analyzed the correlation between FDG uptake and tumor size.

Results

PET/CT imaging revealed all tumors located in each lobe of the two lungs randomly. All 22 tumors were round or oval nodules; 15 had smooth margins, six were lobulated, six were calcified, and one had a ground-glass halo sign. The mean diameter of these tumors was 19.2 ± 7.8 mm (range: 8–34 mm); the mean maximum standardized uptake value (SUVmax) was 2.8 ± 1.3 (range: 1.1–7.4). Sixteen of the lesions exhibited mild to moderate FDG uptake (mean SUVmax 2.3 ± 0.6), and six of the lesions exhibited intense FDG uptake (mean SUVmax 4.3 ± 1.6). A positive correlation was observed between FDG uptake and tumor size (P <0.05).

Conclusion

Single round or ovoid soft-tissue lesions with smooth margins, and mild to moderate FDG uptake on PET/CT images in middle-aged females, suggest a possible diagnosis of PSP. For some atypical cases with intense FDG uptake, a diagnosis of PSP also can be considered. A statistically significant positive correlation was found between SUVmax and PSP lesion size in our study.
99mTc-white blood cell SPECT/CT to assess diabetic foot osteomyelitis remission: contribution of semi-quantitative scoring system
Authors: Vouillarmet Julien , Tordo Jeremie , Moret Myriam , Michon Paul , Morelec Isabelle
Published: March 2021

Aims

We previously reported that 99mTc-White blood cell (WBC) single-photon emission computed tomography (SPECT/CT) could be a useful tool to assess diabetic foot osteomyelitis (DFO) remission and guide the duration of antibiotic treatment. The aim of the present study was to evaluate the performance and reproducibility of two analysis methods to diagnose DFO remission using 99mTc-WBC-SPECT/CT.

Methods

99mTc-WBC-SPECT/CT performed for patients with DFO at the end of antibiotic treatment were retrospectively read by two nuclear physicians (one senior and one junior). Assessment by conventional visual analysis and by the use of a semi-quantitative scoring system, the composite score index (CSI), was performed. The performance and reproducibility of methods were compared between the two nuclear physicians. Successful treatment of DFO was defined by the absence of DFO relapse at the same site within 1 year.

Results

A total of 68 patients with 74 DFO were included. Three were excluded from the analysis due to the low quality of SPECT/CT; among the 71 DFO analyzed, 11 (15.5%) had a relapse during follow-up. Performances of 99mTc-WBC-SPECT/CT to predict DFO remission with conventional visual assessment were significantly lower for junior than for senior nuclear physician with moderate inter-rater agreement (Kappa: 0.417). Performances with the use of CSI were similar between the two readers with good inter-rater agreement (Kappa: 0.756).

Conclusion

The study found that conventional visual assessment of 99mTc-WBC-SPECT/CT to assess DFO remission requires experience, and supported that CSI could be useful for junior nuclear physician to discriminate residual infections and inflammatory post-treatment uptake.
The influence of 68Ga-prostate-specific membrane antigen PET/computed tomography on prostate cancer staging and planning of definitive radiation therapy
Authors: Al-Ibraheem Akram , Abuhijla Fawzi , Salah Samer , Shahait Mohamed , Khader Jamal , Mohamad Issa , Al-Rasheed Ula , Pomykala Kelsey L. , Herrmann Ken , Abu-Hijlih Ramiz
Published: March 2021

Objectives

Prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) is a novel imaging tool with an evolving role in the management of prostate cancer. This study aims to retrospectively evaluate the impact of 68Ga-PSMA PET/CT on prostate cancer staging and definitive radiation therapy planning.

Methods

Between April 2015 and June 2020, 366 men with prostate cancer were evaluated with 68Ga-PSMA PET/CT. Of these, 108 patients had PSMA PET/CT before radiation therapy. Radiation was given as primary treatment in 58 (54%) and as salvage radiation therapy for biochemical recurrence after primary surgery in 50 (46%) patients, respectively. Patient and disease characteristics were analyzed, and impact of PSMA PET/CT on disease staging and radiotherapy planning was evaluated in comparison to conventional imaging.

Results

Median age at presentation was 69 years, and median prostate-specific antigen was 18 ng/mL (3.6–400) for primary and 0.4 ng/mL (0.1–4.6) for salvage radiation, respectively. The combined change of disease stage rate was 36% (39/108) with 45% (26/58) in the subgroup of primary radiation and 26% (13/50) in the patients intended for salvage radiation. Upstaging was found in 24 (22%) and downstaging in 15 (14%) patients. Radiation planning was changed based on PSMA PET/CT in 34 (31%) patients, including 7 (6.4%) patients in which stereotactic body radiotherapy (SBRT) was added to oligometastatic sites. The radiation field was extended to include pelvic lymph node involvement in 21 patients.

Conclusions

68Ga-PSMA PET/CT changed the prostate cancer stage in around one-third of men. PSMA PET/CT significantly impacted radiation planning. Further prospective studies are still required.
Alterations in cerebral glucose metabolism as measured by 18F-fluorodeoxyglucose-PET in patients with persistent postconcussion syndrome
Authors: Teichner Eric M. , You Jason C. , Hriso Chloe , Wintering Nancy A. , Zabrecky George P. , Alavi Abass , Bazzan Anthony J. , Monti Daniel A. , Newberg Andrew B.
Published: March 2021

Background

Many patients who have traumatic brain injury experience a wide range of psychiatric and neurological symptoms (including impairment in functional status, cognition, and mood), and if persistent are referred to as persistent postconcussion syndrome (PCS). To our knowledge, this is the first study to broadly evaluate metabolic dysregulation in a heterogenous patient population meeting the criteria for PCS.

Methods

A total of 64 PCS patients and 37 healthy controls underwent 18F-fluorodeoxyglucose-PET (18F-FDG-PET) scanning, and 70 brain structures (including left and right structures where appropriate) were analyzed in each subject.

Results

Compared to the brains of healthy controls, those of PCS patients demonstrated 15 hypermetabolic and 23 hypometabolic regions. Metabolic changes in the brains of PCS patients were subsequently correlated with various indices of symptom severity, mood, and physical/cognitive function. Among PCS patients, increased metabolism in the right cingulate gyrus correlated with the severity of postconcussion symptoms. Conversely, increased metabolism in the left temporal lobe was associated with both improved mood and measures of adaptability/rehabilitation. Furthermore, increased metabolism in the bilateral orbitofrontal regions correlated with improved working memory.

Conclusions

Overall, these findings suggest a complex pattern of cerebral metabolism in PCS patients, with a mixture of hypometabolic and hypermetabolic regions that correlate with various symptoms, highlighting both potential pathological and compensatory mechanisms in PCS. The findings also suggest that FDG PET is useful for providing neurophysiological information in the evaluation of patients with PCS and may help guide future targeted therapies.
Factors affecting vaccine uptake rate: the story of measles, mumps and rubella
Authors: Downey Tina , Moore John E. , Millar Beverley C.
Published: March 2021

Vaccine uptake can greatly impact on the ability of a country or region to eliminate a disease, which could be detrimental to society if allowed free reign. A high vaccine coverage can produce herd immunity, which confers protection upon the unvaccinated individuals within the population. Although some countries take a voluntary approach to vaccination policies, other countries have mandatory vaccination for specific pathogens. There is a clear inverse correlation between vaccine uptake and incidence of disease and in many countries a trivalent vaccine against measles, mumps and rubella is included in the vaccination schedule. Although naturally acquired immunity is gained from infection by the circulating wild-type virus, the live attenuated vaccine has an effect which wanes over a period of time. In recent years, there has been a global spike in the incidence of both measles and mumps and some authorities are using a third dose of the vaccine to inhibit the spread of any outbreaks which occur. Many factors, such as concerns over vaccine safety and susceptibility to disease have had an impact on vaccine uptake and media bias and misinformation have played a role. With the occurrence of a global pandemic of COVID-19 beginning in late 2019 and continuing for the duration of 2020, access to healthcare and routine vaccination have been affected and vaccine programmes interrupted because of the need for social distancing measures. This may have an impact on future generations, as a significant decline can reduce herd immunity, allowing diseases, which had obtained elimination status to re-emerge.
NUT Midline Carcinoma of the Lung: Computed Tomography Findings in 10 Patients
Authors: Chang Amy Inji , Kim Tae Sung , Han Joungho , Kim Tae Jung , Choi Joon Young
Published: March 2021

Objective

The aim of the study was to evaluate computed tomography (CT) findings of pulmonary NUT midline carcinoma.

Methods

We assessed clinical and CT features of pulmonary NUT carcinoma in 10 consecutive patients (M:F, 7:3; mean, 39 years).

Results

The primary tumors (size range, 15–65 mm) manifested as either a peripheral tumor (5/10) or a central tumor (5/10). All tumors showed relatively low-attenuation at contrast-enhanced CT (mean net enhancement, 26 HU). Associated CT findings were metastatic hilar or mediastinal lymphadenopathy (8/10), ipsilateral pleural seeding with malignant pleural effusion (2/10), and distant metastasis (2/10). Five patients with low tumor-node-metastasis stages after optimal treatment showed no evidence of disease (50%) for 6 to 35 months.

Conclusions

Pulmonary NUT carcinoma presented as a peripheral or a central lung mass showing mild degree of contrast enhancement, frequent metastatic regional lymphadenopathy, affecting relatively young adults. Although known to be highly aggressive, an early diagnosis in low TNM stages can lead to a favorable prognosis.
An integrative model using flow cytometry identifies nosocomial infection after trauma
Authors: Gelbard Rondi B. , Hensman Hannah , Schobel Seth , Stempora Linda L. , Moris Dimitrios , Dente Christopher J. , Buchman Timothy G. , Kirk Allan D. , Elster Eric
Published: March 2021

BACKGROUND

Flow cytometry (FCM) is a rapid diagnostic tool for monitoring immune cell function. We sought to determine if assessment of cell phenotypes using standardized FCM could be used to identify nosocomial infection after trauma.

METHODS

Prospective study of trauma patients at a Level I center from 2014 to 2018. Clinical and FCM data were collected within 24 hours of admission. Random forest (RF) models were developed to estimate the risk of severe sepsis (SS), organ space infection (OSI), and ventilator-associated pneumonia (VAP). Variables were selected using backward elimination and models were validated with leave-one-out.

RESULTS

One hundred and thirty-eight patients were included (median age, 30 years [23–44 years]; median Injury Severity Score, 20 (14–29); 76% (105/138) Black; 60% (83/138) gunshots). The incidence of SS was 8.7% (12/138), OSI 16.7% (23/138), and VAP 18% (25/138). The final RF SS model resulted in five variables (RBCs transfused in first 24 hours; absolute counts of CD56− CD16+ lymphocytes, CD4+ T cells, and CD56 bright natural killer [NK] cells; percentage of CD16+ CD56+ NK cells) that identified SS with an AUC of 0.89, sensitivity of 0.98, and specificity of 0.78. The final RF OSI model resulted in four variables (RBC in first 24 hours, shock index, absolute CD16+ CD56+ NK cell counts, percentage of CD56 bright NK cells) that identified OSI with an AUC of 0.76, sensitivity of 0.68, and specificity of 0.82. The RF VAP model resulted in six variables (Sequential [Sepsis-related] Organ Failure Assessment score: Injury Severity Score; CD4− CD8− T cell counts; percentages of CD16− CD56− NK cells, CD16− CD56+ NK cells, and CD19+ B lymphocytes) that identified VAP with AUC of 0.86, sensitivity of 0.86, and specificity of 0.83.

CONCLUSIONS

Combined clinical and FCM data can assist with early identification of posttraumatic infections. The presence of NK cells supports the innate immune response that occurs during acute inflammation. Further research is needed to determine the functional role of these innate cell phenotypes and their value in predictive models immediately after injury.

LEVEL OF EVIDENCE

Prognostic, level III.
Norovirus Infections in Kidney Transplant Recipients
Authors: Gäckler Anja , Struve Christoph , Mülling Nils , Eisenberger Ute , Korth Johannes , Babel Nina , Kribben Andreas , Fiedler Melanie , Witzke Oliver , Rohn Hana
Published: March 2021

Background.

Norovirus (NoV) infection frequently progresses to chronic disease after kidney transplant (KTx). This study aims to assess potential risk factors helping to determine patients at risk of chronic NoV infection and to analyze the effect of NoV on allograft outcome. Additionally, we assessed the effectiveness of intravenous immunoglobulin (IVIg) therapy for chronic NoV infection.

Methods.

The study enrolled 60 KTx patients requiring hospitalization because of NoV infection. Clinical parameters, severity of NoV infection and potential risk factors were evaluated. Outcome parameters were clinical symptoms, rehospitalizations, persistent shedding of virus, and effects on allograft function.

Results.

Patients were divided into 2 groups: 29 had acute NoV infection only, 31 progressed to chronic NoV infection. Chronic NoV infection was defined as a recurrence of clinical symptoms plus redetection of NoV in stool. Lymphocyte-depleting induction therapy and diabetes mellitus were independent risk factors for chronic infection. For patients with chronic NoV infection, length of stay in hospital was significantly prolonged (P = 0.024). Allograft function remained impaired in the chronic NoV group 6 and 12 mo after initial admission. IVIg was administered to 18 patients with chronic NoV infection. No further clinical symptoms of NoV infection occurred in 13 (72%) of these patients. However, NoV was still detectable in stool specimens from 10 (77%) of these patients.

Conclusions.

Chronic NoV infection is associated with reduced allograft function. Administration of IVIg to patients with chronic NoV infection seems beneficial in achieving freedom from clinical symptoms, despite limited effects on shedding of virus.
Lamp1 mediates lipid transport, but is dispensable for autophagy inDrosophila
Authors: Chaudhry Norin , Sica Margaux , Surabhi Satya , Hernandez David Sanchez , Mesquita Ana , Selimovic Adem , Riaz Ayesha , Bai Hua , Macintosh Gustavo C. , Jenny Andreas
Published: March 2021

The endolysosomal system not only is an integral part of the cellular catabolic machinery that processes and recycles nutrients for synthesis of biomaterials, but also acts as signaling hub to sense and coordinate the energy state of cells with growth and differentiation. Lysosomal dysfunction adversely influences vesicular transport-dependent macromolecular degradation and thus causes serious problems for human health. In mammalian cells, loss of the lysosome associated membrane proteins LAMP1/2 strongly impacts autophagy and cholesterol trafficking. Here we show that the previously uncharacterizedDrosophilaLamp1 is abona fidehomolog of vertebrate LAMP1/2. Surprisingly and in contrast toLamp1/2double mutant mice,DrosophilaLamp1 is not required for viability or autophagy, suggesting that autophagy defects inLamp1/2mutants may have indirect causes. However, Lamp1 deficiency results in an expansion of the acidic compartment in flies. Furthermore, we find thatLamp1mutant larvae have defects in lipid metabolism as they show elevated levels of sterols and diacylglycerols (DAGs). Since DAGs are the main lipid species used for transport though the hemolymph (blood) in insects, our results indicate broader functions of Lamp1 in lipid transport. Our findings makeDrosophilaan ideal model to study the role of LAMP proteins in lipid assimilation without the confounding effects of their storage and without interfering with autophagic processes.
Identification of a novel regulator ofClostridioides difficilecortex formation
Authors: Touchette Megan H. , Benito de la Puebla Hector , Feliciano Carolina Alves , Tanenbaum Benjamin , Schenone Monica , Carr Steven A. , Shen Aimee
Published: March 2021

Clostridioides difficileis a leading cause of healthcare-associated infections worldwide.C. difficileinfections are transmitted by its metabolically dormant, aerotolerant spore form. Functional spore formation depends on the assembly of two protective layers: a thick layer of modified peptidoglycan known as the cortex layer and a multilayered proteinaceous meshwork known as the coat. We previously identified two spore morphogenetic proteins, SpoIVA and SipL, that are essential for recruiting coat proteins to the developing forespore and making functional spores. While SpoIVA and SipL directly interact, the identities of the proteins they recruit to the forespore remained unknown. We used mass spectrometry-based affinity proteomics to identify proteins that interact with the SpoIVA-SipL complex. These analyses identified the Peptostreptococcaceae family-specific, sporulation-induced bitopic membrane protein CD3457 (renamed SpoVQ) as a protein that interacts with SipL and SpoIVA. Loss of SpoVQ decreased heat-resistant spore formation by ∼5-fold and reduced cortex thickness∼2-fold; the thinner cortex layer of ΔspoVQspores correlated with higher levels of spontaneous germination (i.e., in the absence of germinant). Notably, loss of SpoVQ in eitherspoIVAorsipLmutants prevented cortex synthesis altogether and greatly impaired the localization of a SipL-mCherry fusion protein around the forespore. Thus, SpoVQ is a novel regulator ofC. difficilecortex synthesis that appears to link cortex and coat formation. The identification of SpoVQ as a spore morphogenetic protein further highlights how Peptostreptococcaceae family-specific mechanisms control spore formation inC. difficile.

Importance

The Centers for Disease Control has designatedClostridioides difficileas an urgent threat because of its intrinsic antibiotic resistance.C. difficilepersists in the presence of antibiotics in part because it makes metabolically dormant spores. While recent work has shown that preventing the formation of infectious spores can reduceC. difficiledisease recurrence, more selective anti-sporulation therapies are needed. The identification of spore morphogenetic factors specific toC. difficilewould facilitate the development of such therapies. In this study, we identified SpoVQ (CD3457) as a spore morphogenetic protein specific to the Peptostreptococcaceae family that regulates the formation ofC. difficile’sprotective spore cortex layer. SpoVQ acts in concert with the known spore coat morphogenetic factors, SpoIVA and SipL, to link formation of the protective coat and cortex layers. These data reveal a novel pathway that could be targeted to prevent the formation of infectiousC. difficilespores.
Entrepreneurial competences and growth of female-owned enterprises: the mediation role of absorptive capacity
Authors: Dawa Samuel , Namatovu Rebecca , Mulira Fiona , Kyejjusa Sarah , Arinaitwe Mercy , Arinaitwe Alice
Published: March 2021

Purpose

Focusing on female entrepreneurs operating in a resource-scarce environment, this study aims to draw from the resource-based view to examine the relationship between entrepreneurial competences and firm growth.

Design/methodology/approach

This study used a cross-sectional research design. Data was collected from 232 women entrepreneurs operating in Kampala’s two biggest markets. The data were analyzed to test the mediation effect of absorptive capacity on the relationship between entrepreneurial competences and firm growth; a Sobel test and bootstrap estimation were analytical approaches that were used.

Findings

This paper argues that for female entrepreneurs, the venture growth process is not simply dependent on inimitable resources such as competences, as these are first not readily available to female entrepreneurs and second, only provide a temporary competitive advantage. Rather, venture growth also involves the ability to continuously identify and exploit knowledge resources through an absorptive capacity that may be limited by the sociocultural context within which the female entrepreneur operates in sub-Saharan Africa.

Originality/value

The novelty of this research resides in support for the mediating role of the ability to recognize the value of new information, assimilate it and apply it to commercial ends. This study shows that female entrepreneurs use externally generated knowledge as a mechanism to grow their firms and this is impacted by the sociocultural context within which they operate. The study further improves the understanding of the resource-based view by suggesting that a black box exists in the relationship between resources and performance. It is shown that the possession of one resource facilitates the acquisition of other resources and proposes that the role of resources continuously unfolds as a firm develops.
Fitness and fur colouration: Testing the camouflage and thermoregulation hypotheses in an Arctic mammal
Authors: Di Bernardi Cecilia , Thierry Anne‐Mathilde , Eide Nina E. , Bowler Diana E. , Rød‐Eriksen Lars , Blumentrath Stefan , Tietgen Lukas , Sandercock Brett K. , Flagstad Øystein , Landa Arild
Published: March 2021

Selection for crypsis has been recognized as an important ecological driver of animal colouration, whereas the relative importance of thermoregulation is more contentious with mixed empirical support. A potential thermal advantage of darker individuals has been observed in a wide range of animal species. Arctic animals that exhibit colour polymorphisms and undergo seasonal colour moults are interesting study subjects for testing the two alternative hypotheses: demographic performance of different colour morphs might be differentially affected by snow cover with a cryptic advantage for lighter morphs, or conversely by winter temperature with a thermal advantage for darker morphs.

In this study, we explored whether camouflage and thermoregulation might explain differences in reproduction and survival between the white and blue colour morphs of the Arctic fox Vulpes lagopus under natural conditions.

Juvenile and adult survival, breeding propensity and litter size were measured for 798 captive‐bred and released or wild‐born Arctic foxes monitored during an 11‐year period (2007–2017) in two subpopulations in south‐central Norway. We investigated the proportion of the two colour morphs and compared their demographic performance in relation to spatial variation in duration of snow cover, onset of snow season and winter temperatures.

After population re‐establishment, a higher proportion of blue individuals was observed among wild‐born Arctic foxes compared to the proportion of blue foxes released from the captive population. Our field study provides the first evidence for an effect of colour morph on the reproductive performance of Arctic foxes under natural conditions, with a higher breeding propensity of the blue morph compared to the white one. Performance of the two colour morphs was not differentially affected by the climatic variables, except for juvenile survival. Blue morph juveniles showed a tendency for higher survival under colder winter temperatures but lower survival under warmer temperatures compared to white morph juveniles.

Overall, our findings do not consistently support predictions of the camouflage or the thermoregulation hypotheses. The higher success of blue foxes suggests an advantage of the dark morph not directly related to disruptive selection by crypsis or thermoregulation. Our results rather point to physiological adaptations and behavioural traits not necessarily connected to thermoregulation, such as stress response, immune function, sexual behaviour and aggressiveness. Our findings highlight the need to explore the potential role of genetic linkage or pleiotropy in influencing the fitness of white and blue Arctic foxes as well as other species with colour polymorphisms.
Oral mycophenolate mofetil in the treatment of acquired dermal macular hyperpigmentation: An open‐label pilot study
Authors: Bishnoi Anuradha , Vinay Keshavamurthy , Parsad Davinder , Kumar Sheetanshu , Chatterjee Debajyoti , Nahar Saikia Uma , Sendhil Kumaran Muthu
Published: March 2021

Background

Literature on treating acquired dermal macular hyperpigmentation is sparse.

Aims and objectives

To assess treatment response of mycophenolate mofetil in patients having acquired dermal macular hyperpigmentation.

Material and Methods

In this open‐label, pilot study, patients of acquired dermal macular hyperpigmentation affecting at least the face and/or neck were included. Each participant was treated with mycophenolate mofetil 2 g/day for 24 weeks, with a follow‐up of 12 weeks. Two aspects of disease severity were measured: activity (appearance of new lesions/extension of existing lesions), and degree of hyperpigmentation (measured using ‘dermal pigmentation area and severity index’). Patient satisfaction was assessed on a scale of 0–10.

Results

Forty‐three of 46 patients who were prescribed mycophenolate, completed the study (40 females, 6 males; mean disease duration 2.8 ± 1.4 years). Amongst 20 (43.5%) patients with active disease, stability was achieved in 17, after a mean duration of 6.1 ± 2.5 weeks (range 4–12 weeks; median 4; IQR 4 weeks). Mean dermal pigmentation area and severity index at baseline was 18.8 ± 7.1 and decreased to 13.7 ± 6.3 at 24th week (27.5 ± 14.7%; P < 0.001). A significant decreasing trend in dermal pigmentation area and severity index (P < 0.001) was observed, and first significant difference from baseline was noted at the 16th week (P 0.008). Less than 10%, >10–20%, >20%–30%, >30%–40%, >40%–50%, and >50% reduction in dermal pigmentation area and severity index was observed in 8, 5, 4, 15, 10 and 1 patients/patient respectively. The maximum mean grade of pre‐treatment dermatoscopic severity was 3 ± 0.7, and decreased to 2.1 ± 0.8 on the face (P < 0.001) and 2.4 ± 0.7 on the neck (P < 0.001) post‐treatment. There were 9 (20.1%) non‐responders. Self‐assessment scores of the rest of the patients fell in the range of moderate/fair improvement (>5 to 7). No significant correlation was seen between patient satisfaction score and degree of reduction in dermal pigmentation area and severity index (r −0.39). Three developed adverse effects (leucopenia, n = 1; transaminitis and hyperbilirubinemia, n = 2) that resolved following discontinuation of mycophenolate.

Conclusion

Mycophenolate mofetil appears to be a promising treatment option in acquired dermal macular hyperpigmentation.
Long‐term antihypertensive drug use and risk of cancer: The Japan Public Health Center‐based prospective study
Authors: Matsui Satoshi , Sobue Tomotaka , Zha Ling , Kitamura Tetsuhisa , Sawada Norie , Iwasaki Motoki , Shimazu Taichi , Tsugane Shoichiro
Published: March 2021

Antihypertensive drugs have been reported as both promotors and suppressors of cancers and this relationship has been known for several decades. We examined a large‐scale prospective cohort study in Japan to assess the relationship between long‐term antihypertensive drug use, for 10 y, and carcinogenesis. We divided participants into 4 categories according to the period of antihypertensive drug use, and calculated the hazard ratios (HRs), 95% confidence intervals (CIs), and P trends using the Cox proportional hazard model. In all cancers, there was a significant difference in the medication period and the adjusted HR, as well as a significant difference in the P trend. Furthermore, more than 10 y use of antihypertensive drugs significantly increased the adjusted HR in colorectal cancer (multivariable HR: 1.18, 95% CI: 1.01‐1.37 in the >10 y use group; P for trend = .033) and renal cancer (multivariable HR: 3.76, 95% CI: 2.32‐6.10 in the 5‐10 y use group; multivariable HR: 2.14, 95% CI: 1.29‐3.56 in the >10 y use group; P for trend < .001). The highest adjusted HR in renal cancer among antihypertensive drug users was observed in the analysis performed on patients in which the outcomes were calculated from 3 y after the 10‐y follow‐up survey and by sex. A large‐scale cohort study in Japan suggested that long‐term use of antihypertensive drugs may be associated with an increased incidence of colorectal and renal cancer.
Impact of carboxylesterase 1 genetic polymorphism on trandolapril activation in human liver and the pharmacokinetics and pharmacodynamics in healthy volunteers
Authors: Wang Xinwen , Her Lucy , Xiao Jingcheng , Shi Jian , Wu Audrey H. , Bleske Barry E. , Zhu Hao‐Jie
Published: March 2021

Trandolapril, an angiotensin‐converting enzyme inhibitor prodrug, needs to be activated by carboxylesterase 1 (CES1) in the liver to exert its intended therapeutic effect. A previous in vitro study demonstrated that the CES1 genetic variant G143E (rs71647871) abolished CES1‐mediated trandolapril activation in cells transfected with the variant. This study aimed to determine the effect of the G143E variant on trandolapril activation in human livers and the pharmacokinetics (PKs) and pharmacodynamics (PDs) in human subjects. We performed an in vitro incubation study to assess trandolapril activation in human livers (5 G143E heterozygotes and 97 noncarriers) and conducted a single‐dose (1 mg) PK and PD study of trandolapril in healthy volunteers (8 G143E heterozygotes and 11 noncarriers). The incubation study revealed that the mean trandolapril activation rate in G143E heterozygous livers was 42% of those not carrying the variant (p = 0.0015). The clinical study showed that, relative to noncarriers, G143E carriers exhibited 20% and 15% decreases, respectively, in the peak concentration (Cmax) and area under the curve from 0 to 72 h (AUC0–72 h) of the active metabolite trandolaprilat, although the differences were not statistically significant. Additionally, the average maximum reductions of systolic blood pressure and diastolic blood pressure in carriers were ~ 22% and 23% less than in noncarriers, respectively, but the differences did not reach a statistically significant level. In summary, the CES1 G143E variant markedly impaired trandolapril activation in the human liver under the in vitro incubation conditions; however, this variant had only a modest impact on the PK and PD of trandolapril in healthy human subjects.
Reducing climate impacts of beef production: A synthesis of life cycle assessments across management systems and global regions
Authors: Cusack Daniela F. , Kazanski Clare E. , Hedgpeth Alexandra , Chow Kenyon , Cordeiro Amanda L. , Karpman Jason , Ryals Rebecca
Published: March 2021

The global demand for beef is rapidly increasing (FAO, 2019), raising concern about climate change impacts (Clark et al., 2020; Leip et al., 2015; Springmann et al., 2018). Beef and dairy contribute over 70% of livestock greenhouse gas emissions (GHG), which collectively contribute ~6.3 Gt CO2‐eq/year (Gerber et al., 2013; Herrero et al., 2016) and account for 14%–18% of human GHG emissions (Friedlingstein et al., 2019; Gerber et al., 2013). The utility of beef GHG mitigation strategies, such as land‐based carbon (C) sequestration and increased production efficiency, are actively debated (Garnett et al., 2017). We compiled 292 local comparisons of “improved” versus “conventional” beef production systems across global regions, assessing net GHG emission data from Life Cycle Assessment (LCA) studies. Our results indicate that net beef GHG emissions could be reduced substantially via changes in management. Overall, a 46 % reduction in net GHG emissions per unit of beef was achieved at sites using carbon (C) sequestration management strategies on grazed lands, and an 8% reduction in net GHGs was achieved at sites using growth efficiency strategies. However, net‐zero emissions were only achieved in 2% of studies. Among regions, studies from Brazil had the greatest improvement, with management strategies for C sequestration and efficiency reducing beef GHG emissions by 57%. In the United States, C sequestration strategies reduced beef GHG emissions by over 100% (net‐zero emissions) in a few grazing systems, whereas efficiency strategies were not successful at reducing GHGs, possibly because of high baseline efficiency in the region. This meta‐analysis offers insight into pathways to substantially reduce beef production's global GHG emissions. Nonetheless, even if these improved land‐based and efficiency management strategies could be fully applied globally, the trajectory of growth in beef demand will likely more than offset GHG emissions reductions and lead to further warming unless there is also reduced beef consumption.
Certified Nurse‐Midwives in Rural Kansas Hospitals: A Survey of Senior Hospital Administrators
Authors: Koschwanez Heidi , Harrington Jamie , Fischer Mary L , Beck Emma , Kennedy Michael
Published: March 2021

Introduction

Little is known about the nurse‐midwifery workforce in rural Kansas hospitals, despite Kansas facing a shortage of primary care physicians providing maternity care rurally. This study investigated the current number of hospitals with certified nurse‐midwives (CNMs) with privileges to attend births in Kansas hospitals located in frontier, rural, and densely settled rural counties and anticipated trends in the size of the CNM workforce at hospitals over the next 5 years.

Methods

Electronic surveys were distributed to senior hospital administrators at 94 hospitals in rural Kansas from June to July 2019. The survey included both open and closed‐ended questions related to scope of CNM privileges, collaborative agreements, and forecasted trends in the CNM workforce in rural Kansas.

Results

Fifty‐six hospitals completed the survey. Only one hospital reported having CNM‐attended births. Twenty‐eight of 37 hospital administrators agreed CNMs should have collaborative agreements with physicians. Most respondents did not anticipate the number of CNMs with privileges to increase at their hospitals over the next 5 years.

Discussion

Future research should focus on understanding the factors limiting CNM expansion in rural Kansas, because CNMs represent an untapped, additional maternity care workforce for rural Kansas.
Implementing Full‐Body Movements in a Verbal Memory Task: Searching for Benefits but Finding Mainly Costs
Authors: Amico Gianluca , Schaefer Sabine
Published: March 2021

Studies on “embodiment” show that moving your body can enhance cognition. We investigated such effects in a verbal memory task across age. In Study 1, children, adolescents, and young adults (N = 148) were tested in group sessions and reproduced number series of increasing length. In the “embodied” condition, subjects walked to numbered gymnastic mats. In the “sitting” condition, the numbers were presented visually. All age groups, except the youngest, showed a deterioration of verbal memory performance in the embodied condition compared to sitting. In Study 2, young adults (n = 33, Mage = 24.5 years) and children (n = 28, Mage = 7.3 years) were tested individually, with smaller target fields. There were no differences in verbal memory performance between the conditions. This indicates that “embodiment” does not always lead to performance enhancements. Instead, moving through space while thinking represents a dual‐task situation, causing performance decrements across age.
Developing a Nicotiana benthamiana transgenic platform for high‐value diterpene production and candidate gene evaluation
Authors: Forestier Edith C.F. , Czechowski Tomasz , Cording Amy C. , Gilday Alison D. , King Andrew J. , Brown Geoffrey D. , Graham Ian A.
Published: March 2021

To engineer Nicotiana benthamiana to produce novel diterpenoids, we first aimed to increase production of the diterpenoid precursor geranylgeranyl pyrophosphate (GGPP) by up‐regulation of key genes of the non‐mevalonate (MEP) pathway sourced from Arabidopsis thaliana. We used transient expression to evaluate combinations of the eight MEP pathway genes plus GGPP synthase and a Jatropha curcas casbene synthase (JcCAS) to identify an optimal combination for production of casbene from GGPP. AtDXS and AtHDR together with AtGGPPS and JcCAS gave a 410% increase in casbene production compared to transient expression of JcCAS alone. This combination was cloned into a single construct using the MoClo toolkit, and stably integrated into the N. benthamiana genome. We also created multigene constructs for stable transformation of two J. curcas cytochrome P450 genes, JcCYP726A20 and JcCYP71D495 that produce the more complex diterpenoid jolkinol C from casbene when expressed transiently with JcCAS in N. benthamiana. Stable transformation of JcCYP726A20, JcCYP71D495 and JcCAS did not produce any detectable jolkinol C until these genes were co‐transformed with the optimal set of precursor‐pathway genes. One such stable homozygous line was used to evaluate by transient expression the involvement of an ‘alkenal reductase’‐like family of four genes in the further conversion of jolkinol C, leading to the demonstration that one of these performs reduction of the 12,13‐double bond in jolkinol C. This work highlights the need to optimize precursor supply for production of complex diterpenoids in stable transformants and the value of such lines for novel gene discovery.