bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Analgesic Efficacy and Opioid-sparing Effect of Duloxetine After Arthroscopic Rotator Cuff Repair
Authors: Su Peng , Pang Long , Li Shu , Sun Weihao , Zhao Yanmin , Fu Weili , Li Jian , Tang Xin
Published: March 2022

Objective:

This study aimed to evaluate the analgesic efficacy and opioid-sparing effect of duloxetine in adults having arthroscopic rotator cuff repair, as well as its clinical safety.

Methods:

In this randomized trial, 120 adults having arthroscopic rotator repair were randomized to receive perioperative oral duloxetine or placebo. The primary outcome was patient self-reported pain score (Visual Analog Scale: 0 to 10) at rest and opioid consumption within postoperative 2 days. Other outcomes included adverse effects, changes of thromboelastogram, and hemoglobin indicators before and after the operation.

Results:

A total of 120 patients were included in the intention-to-treat analysis, of which 60 received duloxetine and 60 received placebo. Groups were similar on the demographic, baseline, and intraoperative variables. There were significant differences in pain scores at rest at postoperative 3, 6, 12, 24, and 48 hours (3 h: P=0.001; 6 h: P=0.001; 12 h: P=0.001; 24 h: P=0.005; 48 h: P=0.034) and at movement at postoperative 6, 12, and 48 hours (6 h: P=0.004; 12 h: P=0.002; 48 h: P=0.033), while none of the differences met the minimum clinically important difference. There were no significant differences in opioid consumption and in hemoglobin and thromboelastogram before and after operation between the duloxetine group and the placebo group (all P>0.05). For adverse effects, the incidence of nausea and vomiting in the duloxetine group was significantly higher than that in the placebo group (P=0.018).

Discussion:

For patients undergoing arthroscopic rotator cuff repairs, duloxetine resulted in a significant reduction in pain within postoperative 2 days, but the reduction was not clinically meaningful. Duloxetine did not decrease the opioid consumption within postoperative 2 days and did not increase the risk of bleeding within postoperative 2 days. The incidence of nausea and vomiting in the duloxetine group was significantly greater than that in the placebo group.
Using Skeletal Maturity in Pediatric Orthopaedics: A Primer
Authors: Furdock Ryan J. , Sanders James O. , Cooperman Daniel R. , Liu Raymond W.
Published: March 2022

This article provides researchers with the background and guidance necessary to practically incorporate skeletal maturity estimation into any study of adolescents with imaging of the shoulder, elbow, hand, hip, knee, or foot. It also provides clinicians with a comprehensive, concise synopsis of systems that can be used to estimate skeletal maturity in clinical practice. In the article, we provide a relatively brief overview of each currently available skeletal maturity system that has been validated on a longitudinal dataset. The supplementary files include 2 PowerPoint files for each skeletal maturity system. The first PowerPoint file offers examples and instructions for using each radiographic system. The second PowerPoint file includes 20 graded radiographs that can be used for reliability analyses in the research setting. We have also developed a free mobile application available on the iOS and Android platforms named “What’s the Skeletal Maturity?” that allows clinicians to rapidly estimate skeletal maturity on any patient using any commonly obtained orthopaedic radiograph.
Move in the Tube Sternal Precautions: A Retrospective Analysis of a Single Inpatient Rehabilitation Facility
Authors: McKenna Heather , Jones Jennifer , Harmon Erin Y.
Published: March 2022

Purpose:

To assess the admitting characteristics, adverse events, and rehabilitation outcomes of patients adhering to move in the tube (MIT) or standard sternal precautions in an inpatient rehabilitation facility (IRF).

Methods:

This study is a retrospective analysis of 273 patients admitted to a single IRF. Patients followed the sternal precautions recommended by their admitting acute care hospitals. One hundred ninety patients' assigned standard and 83 patients' assigned MIT sternal precautions were evaluated. Admitting characteristics, including comorbidities and functional status, were compared between cohorts. Hospital readmissions, sternal disruptions, length of stay, functional independence at discharge, and discharge destination were also assessed.

Results:

Patients adhering to MIT precautions had higher levels of functional independence at admission despite a higher frequency of combined coronary artery bypass grafts/valve surgeries, comorbidities, and prior functional limitations. There was no difference in sternal wound disruptions, return to hospital rates, length of IRF stay, or functional independence levels at discharge between cohorts.

Conclusions:

Patients on MIT precautions were admitted to an IRF with more medical complications but higher functional independence. Both groups had minimal sternal complications, providing evidence that modified sternal precautions are safe and can benefit patients in an IRF setting.
Sinonasal Mucosal Melanoma: An Update and Review of the Literature
Authors: Salari Behzad , Foreman Ruth K. , Emerick Kevin S. , Lawrence Donald P. , Duncan Lyn M.
Published: March 2022

Primary sinonasal mucosal melanoma (SNMM) is an aggressive tumor with high metastatic potential and poor outcomes. Presenting symptoms are nonspecific, and the nasal cavity is the most common site of origin followed by the maxillary and ethmoid sinuses. Histopathologically, SNMMs are pleomorphic and predominantly composed of epithelioid cell type. Identifying these tumors requires a high index of suspicion for melanoma and the use of a panel of immunohistochemical markers when typical histopathological features are missing. Not infrequently, these tumors are undifferentiated and/or amelanotic. Currently, SNMM falls into 2 different staging systems proposed by the American Joint Committee on Cancer, one for carcinoma of the nasal cavity and sinuses and the other for head and neck melanoma. Although therapeutic standards do not exist, surgical resection with adjuvant radiotherapy and/or systemic therapy may offer the best outcome. Lymphadenectomy including possible parotidectomy and neck dissection should be considered in patients with regional lymph node metastasis. However, the role of elective lymph node dissection is controversial. Genetic profiling has identified a number of recurrent gene mutations that may prove useful in providing targets for novel, emerging biological treatments. In this article, we provide an update on clinicopathological features, staging, molecular discoveries, and treatment options for SNMM.
Bulboma: A Benign Keratosis With Differentiation Toward the Lower Segment of the Hair Follicle
Authors: Sidlow Jonathan S. , Reichel Martin
Published: March 2022

Bulboma is an appellation proposed to designate a distinctive solitary keratosis exhibiting differentiation toward the bulb of the lower segment of the hair follicle. Bulboma is composed of a papillated proliferation of epithelial cells beneath which is a broad front of interconnected follicular papillae. Overlying these coalescing follicular papillae are follicular germinative cells ascending into matrical cells and supramatrical cells. Cells demonstrating differentiation toward Huxley's and Henle's layer of the inner root sheath at the level of the bulb are present including strikingly bright eosinophilic trichohyalin granules and the blue-grey corneocytes of the stem. There is overlying hypergranulosis and orthokeratosis. The clinical and histopathological findings in 4 cases of bulboma, a rare, benign solitary keratosis are presented.
A Rare Case of Primary Cutaneous Signet-Ring Cell Melanoma With Discrepant Findings on Gene Expression Profiling and Chromosomal Microarray Analysis
Authors: Boothby-Shoemaker Wyatt , Kwa Michael , Kohen Laurie , Shaw Brandon , Friedman Ben J.
Published: March 2022

Melanoma with signet ring cell features is an exceptionally rare variant of primary cutaneous and metastatic melanoma. The molecular mechanisms underlying this unusual cytologic phenotype in malignant melanocytes are largely unknown. In this report, we aim to add to the literature by describing the histomorphological, immunophenotypic, gene expression, and cytogenetic findings in 1 recently encountered case.
Predictors of Stimulant Medication Continuity in Children with Attention-Deficit/Hyperactivity Disorder
Authors: Kamimura-Nishimura Kelly I. , Brinkman William B. , Epstein Jeffery N. , Zhang Yin , Altaye Mekibib , Simon John , Modi Avani C. , Froehlich Tanya E.
Published: March 2022

Objective:

The objective of this study was to examine the simultaneous impact of patient-related and parent-related factors, medication-related factors, and health care system-related factors on attention-deficit/hyperactivity disorder (ADHD) medication continuity.

Method:

Stimulant-naïve children (N = 144, Mage = 8 yrs, 71% male) with ADHD completed a methylphenidate (MPH) trial and were followed for 1 year after trial completion and return to community care. Multivariable analysis investigated predictors of (1) having at least 1 filled ADHD prescription after return to community care versus none and (2) having more days covered with medicine after return to community care. Predictors included race; age; sex; income; baseline ADHD symptom severity; MPH trial experience; child and parent mental health conditions; and parent beliefs about ADHD, ADHD medications, and therapeutic alliance.

Results:

One hundred twenty-one children (84%) had at least 1 filled ADHD medication prescription (mean = 178 d covered by medication) in the year after return to community care. Multivariable models found that a weaker perceived clinician-family working alliance predicted not filling any ADHD prescriptions. Among those who filled ≥1 prescription, factors linked to fewer days of ADHD medication coverage included child sociodemographic factors (non-White race, older age, being female, and lower income), lower parent beliefs that the child's ADHD affects their lives, and higher parent beliefs that medication is harmful, while child oppositional defiant disorder and parental ADHD predicted having more days of medication coverage.

Conclusion:

Child demographic factors, parent beliefs, and medication-related factors are associated with continuation of ADHD medication. These findings may facilitate the development of effective strategies to improve ADHD medication continuity for children from diverse groups.
Evaluation and Management of Lower GI Bleeding
Authors: Drezdzon Melissa K. , Peterson Kent J.
Published: March 2022

CASE SUMMARY:

A 73-year-old woman, who had received apixaban for therapeutic anticoagulation, presented with hypotension and hematochezia. After resuscitation, diagnostic colonoscopy revealed multiple polyps and old blood within the colonic lumen, but no active bleeding (Fig. 1). Nasogastric lavage and subsequent EGD were unremarkable. During her hospitalization, she was admitted to the intensive care unit with worsening anemia, hypotension, and hematochezia. CT angiogram showed extravasation at the transverse colon (Fig. 1). Formal angiogram was unable to localize the source of bleeding, despite provocation. Given the localization on CT angiography and the patient’s clinical deterioration, she underwent hand-assisted segmental transverse colectomy. Surgical pathology was notable for multiple adenomas without dysplasia. The patient had no further episodes of GI bleeding after resection.
Comprehensive Evaluation of the Lower Eyelid Aging Process Among Asian Women
Authors: Cheng Chun-Yu , Hu Sindy , Chang Shyue-Luen , Lee Mei-Ching , Huang Yau-Li
Published: March 2022

BACKGROUND

Lower eyelid aging is a complicated process, and for that reason, a comprehensive assessment of the lower eyelid is important before treatment.

OBJECTIVE

This study was conducted to analyze and assess the lower eyelid aging process between different age groups of Asian women.

METHODS AND MATERIALS

The authors developed the comprehensive lower eyelid age rating scale (CLEARS). The rating scale contains 3 domains and each composed of 3 items. Individuals were evaluated by the age group starting with the third decade (20–29 years) through the seventh decade (60–69 years) by 2 dermatologists working independently.

RESULTS

A total of 114 cases were evaluated. The total scores of CLEARS increased significantly between each adjacent age group. The scores of the snap test and the severity of fine lines, nasojugal groove, midcheek furrow, and eye bags increased significantly from the 3rd decade. The scores of the distraction test and the severity of palpebromalar groove and malar mound begin to increase with the 4th decade. Kappa coefficients of all items achieved moderate to substantial agreement.

CONCLUSION

This study describes the lower eyelid aging process among Asian women by CLEARS assessment. Lower eyelid aging becomes progressively more notable beginning with the third decade.
QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY REVEALS ROD PHOTORECEPTOR DEGENERATION in EARLY DIABETIC RETINOPATHY
Authors: Le David , Son Taeyoon , Lim Jennifer I. , Yao Xincheng
Published: March 2022

Purpose:

This study is to test the feasibility of optical coherence tomography (OCT) detection of photoreceptor abnormality and to verify that the photoreceptor abnormality is rod predominated in early diabetic retinopathy (DR).

Methods:

OCT images were acquired from normal eyes, diabetic eyes with no DR, and mild nonproliferative DR (NPDR). Quantitative features, including thickness measurements quantifying band distances and reflectance intensity features among the external limiting membrane, inner segment ellipsoid, interdigitation zone, and retinal pigment epithelium were determined. Comparative OCT analysis of central fovea, parafovea, and perifovea were implemented to verify that the photoreceptor abnormality is rod predominated in early DR.

Results:

Thickness abnormalities between the inner segment ellipsoid and interdigitation zone also showed a decreasing trend among cohorts. Reflectance abnormalities of the external limiting membrane, interdigitation zone, and inner segment ellipsoid were observed between healthy, no DR, and mild NPDR eyes. The normalized inner segment ellipsoid/retinal pigment epithelium intensity ratio revealed a significant decreasing trend in the perifovea, but no detectable difference in central fovea.

Conclusion:

Quantitative OCT analysis consistently revealed outer retina, i.e., photoreceptor changes in diabetic patients with no DR and mild NPDR. Comparative analysis of central fovea, parafovea, and perifovea confirmed that the photoreceptor abnormality is rod-predominated in early DR.
A predictive model incorporating inflammation markers for high-grade surgical complications following liver resection for hepatocellular carcinoma
Authors: Wu Hsiang-Ling , Liu Hsin-Yi , Liu Wan-Chi , Hou Ming-Chih , Tai Ying-Hsuan
Published: March 2022

Background:

Systemic inflammation and immune deficiency predispose surgical patients to infection and adversely affect postoperative recovery. We aimed to evaluate the prognostic ability of inflammation and immune-nutritional markers and to develop a predictive model for high-grade complications after resection of hepatocellular carcinoma (HCC).

Methods:

This study enrolled 1431 patients undergoing liver resection for primary HCC at a medical center. Preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, prognostic nutritional index, Model for End-Stage Liver Disease score, Albumin-Bilirubin score, Fibrosis-4 score, and Aspartate Aminotransferase to Platelet Ratio Index score were assessed. Stepwise backward variable elimination was conducted to determine the factors associated with Clavien-Dindo grade III to V complications within 30-day postoperative period. The predictive model was internally validated for discrimination performance using area under the receiver operating characteristic curve (AUC).

Results:

A total of 106 (7.4%) patients developed high-grade complications. Four factors independently predicted a high-grade postoperative complication and were integrated into the predictive model, including NLR (adjusted odds ratio: 1.10, 95% confidence interval [CI], 1.02-1.19), diabetes mellitus, extent of hepatectomy, and intraoperative blood loss. The AUC of the model was 0.755 (95% CI, 0.678-0.832) in the validation dataset. Using the cutoff value based on Youden’s index, the sensitivity and specificity of the risk score were 59.0% and 76.3%, respectively.

Conclusion:

Preoperative NLR independently predicted a high-grade complication after resection of HCC. The predictive model allows for identification of high-risk patients and appropriate modifications of perioperative care to improve postoperative outcomes.
Changes in Cervical Cytology Results and Human Papillomavirus Types Among Persons Screened for Cervical Cancer, 2007 and 2015–2017
Authors: Lewis Rayleen M. , Naleway Allison L. , Klein Nicola P. , Crane Bradley , Hsiao Amber , Aukes Laurie , Timbol Julius , Querec Troy D. , Steinau Martin , Weinmann Sheila , Unger Elizabeth R. , Markowitz Lauri E.
Published: March 2022

Objectives

Since 2006, the US human papillomavirus (HPV) vaccination program has led to decreases in HPV infections caused by high-risk vaccine-targeted HPV types (HPV 16/18). We assessed differences in high-risk HPV prevalence by cervical cytology result among 20- to 24-year-old persons participating in routine cervical cancer screening in 2015–2017 compared with 2007.

Materials and Methods

Residual routine cervical cancer screening specimens were collected from 20- to 24-year-old members of 2 integrated healthcare delivery systems as part of a cross-sectional study and were tested for 37 HPV types. Cytology results and vaccination status (≥1 dose) were extracted from medical records. Cytology categories were normal, atypical squamous cells of undefined significance, low-grade squamous intraepithelial lesions (SIL), or high-grade SIL/atypical squamous cells cannot exclude high-grade SIL. Prevalences of HPV categories (HPV 16/18, HPV 31/33/45/52/58, HPV 35/39/51/56/59/66/68) were estimated by cytology result for 2007 and 2015–2017.

Results

Specimens from 2007 (n = 4046) were from unvaccinated participants; 4574 of 8442 specimens (54.2%) from 2015–2017 were from vaccinated participants. Overall, HPV 16/18 positivity was lower in 2015–2017 compared with 2007 in all groups: high-grade SIL/atypical squamous cells cannot exclude high-grade SIL, 16.0% vs 69.2%; low-grade SIL, 5.4% vs 40.1%; atypical squamous cells of undefined significance, 5.0% vs 25.6%; and normal, 1.3% vs 8.1%. Human papillomavirus 31/33/45/52/58 prevalence was stable for all cytology groups; HPV 35/39/51/56/59/66/68 prevalence increased among low-grade SIL specimens (53.9% to 65.2%) but remained stable in other groups.

Conclusions

Prevalence of vaccine-targeted high-risk HPV types 16/18 was dramatically lower in 2015–2017 than 2007 across all cytology result groups while prevalence of other high-risk HPV types was mainly stable, supporting vaccine impact with no evidence of type replacement.
Aspirin Use and the Risk of Hepatocellular Carcinoma
Authors: Wang Yikai , Wang Muqi , Liu Chenrui , Wang Wenjun , Shi Juanjuan , Dang Shuangsuo
Published: March 2022

Introduction and Aim:

The use of aspirin is a potential protective factor against the development of hepatocellular carcinoma (HCC). Therefore, we conducted a meta-analysis to evaluate the contribution of aspirin to the risk of HCC.

Methods:

We searched for PubMed and EMBASE through September 2021.

Results:

Eighteen studies (16 cohort, 2 case-control) were included. Aspirin users were less likely to develop HCC than nonusers [adjusted odds ratio (OR), 0.54; 95% confidence interval (CI): 0.44-0.66]. Stratified analysis showed that aspirin reduced the risk of HCC in Asian and Western populations (OR, 0.59 vs. 0.67). Besides, aspirin has protective effects against HCC after hepatitis B virus (OR, 0.70; 95% CI: 0.52-0.93) and hepatitis C virus infections (OR, 0.41; 95% CI: 0.23-0.73). Aspirin has protective effects on people with chronic liver disease (OR, 0.46; 95% CI: 0.31-0.67) and on the general population (OR, 0.65; 95% CI: 0.54-0.79). In addition, confounding factors have an important impact on the results of aspirin prevention of liver cancer before (OR, 0.28; 95% CI: 0.06-1.27) and after (OR, 0.58; 95% CI: 0.47-0.71) adjustment. Further studies have shown that those in the long duration group do not experience better effects in preventing HCC (OR, 0.62 vs. 0.63). A further meta-analysis of 3 articles showed that the use of aspirin did not increase the risk of bleeding in patients with HCC (OR, 1.19; 95% CI: 0.87-1.64).

Conclusion:

Our meta-analysis shows that the use of aspirin is associated with a lower risk of liver cancer.
Measuring Inconsistency in Quality Across Patient Groups to Target Quality Improvement
Authors: Agniel Denis , Martino Steven C. , Burkhart Q. , Hudson Scholle Sarah , Quigley Denise D. , Hambarsoomian Katrin , Orr Nate , Maksut Jessica L. , Darabidian Biayna , Elliott Marc N.
Published: March 2022

Background:

Quality improvement (QI) may be aimed at improving care for all patients, or it may be targeted at only certain patient groups. Health care providers have little guidance when determining when targeted QI may be preferred.

Objectives:

The aim was to develop a method for quantifying performance inconsistency and guidelines for when inconsistency indicates targeted QI, which we apply to the performance of health plans for different patient groups.

Research Design and Measures:

Retrospective analysis of 7 Health Care Effectiveness Data and Information Set (HEDIS) measures of clinical care quality.

Subjects:

All Medicare Advantage (MA) beneficiaries eligible for any of 7 HEDIS measures 2015–2018.

Results:

MA plans with higher overall performance tended to be less inconsistent in their performance (r=−0.2) across groups defined by race-and-ethnicity and low-income status (ie, dual eligibility for Medicaid or receipt of Low-Income Subsidy). Plan characteristics were usually associated with only small differences in inconsistency. The characteristics associated with differences in consistency [eg, size, Health Maintenance Organization (HMO) status] were also associated with differences in overall performance. We identified 9 (of 363) plans that had large inconsistency in performance across groups (>0.8 SD) and investigated the reasons for inconsistency for 2 example plans.

Conclusions:

This newly developed inconsistency metric may help those designing and evaluating QI efforts to appropriately determine when targeted QI is preferred. It can be used in settings where performance varies across groups, which can be defined by patient characteristics, geographic areas, hospital wards, etc. Effectively targeting QI efforts is essential in today’s resource-constrained health care environment.
Self-reported health condition severity and ambulation status postmajor dysvascular limb loss
Authors: Mayo Amanda L. , Viana Ricardo , Dilkas Steven , Payne Michael , Devlin Michael , MacKay Crystal , Cimino Stephanie R. , Guilcher Sara J. T. , Hitzig Sander L.
Published: March 2022

Background:

Individuals with dysvascular lower limb amputations (LLA) secondary to complications of peripheral arterial disease (PAD) and/or diabetes have high rates of co-morbidities.

Objectives:

To describe self-reported health condition severity and their association with sociodemographic factors and ambulations status among individuals with major dysvascular LLA.

Study Design:

Cross sectional telephone and in person survey with adults with major dysvascular LLA living in the community setting in Ontario, Canada.

Methods:

Survey by phone/in person, and completion of the Dysvascular Conditions Scale and Special Interest in Amputee Medicine Mobility (SIGAM) Grade by each participant.

Results:

Two hundred thirty-one individuals with major dysvascular LLAs participated in the study. Most of them were male individuals (80.5%) and had undergone a transtibial amputation (74%). On average, participants were 3.4 years postlimb loss and had five identified Dysvascular Conditions Scale health conditions. The top five reported health conditions were diabetes, hypertension, phantom limb pain, musculoskeletal pain, and back pain. With the exclusion of hypertension, these conditions were also perceived by respondents to be quite severe for their impact. Vision impairment was also rated as being severe in nature. Lower mobility Special Interest Group in Amputee Medicine grades were associated with higher health condition severity scores.

Conclusions:

Individuals with dysvascular limb loss experience high multimorbidity with perceived negative impact on their overall wellness and function. Rehabilitation and self-management strategies to help patients with dysvascular LLAs to manage chronic health conditions may improve outcomes.
Regulation of Escherichia coli fim gene transcription by GadE and other acid tolerance gene products
Authors: Schwan William R. , Luedtke Joshua , Engelbrecht Kathleen , Mollinger Jeremy , Wheaton Andrew , Foster John W. , Wolchak Robert
Published: March 2022

Uropathogenic

Escherichia coli

(UPEC) cause millions of urinary tract infections each year in the United States. Type 1 pili are important for adherence of UPEC to uroepithelial cells in the human and murine urinary tracts where osmolality and pH vary. Previous work has shown that an acidic pH adversely affects the expression of type 1 pili. To determine if acid tolerance gene products may be regulating E. coli fim gene expression, a bank of K-12 strain acid tolerance gene mutants were screened using fimA-lux, fimB-lux, and fimE-lux fusions on single copy number plasmids. We have determined that a mutation in gadE increased transcription of all three fim genes, suggesting that GadE may be acting as a repressor in a low pH environment. Complementation of the gadE mutation restored fim gene transcription to wild-type levels. Moreover, mutations in gadX, gadW, crp, and cya also affected transcription of the three fim genes. To verify the role GadE plays in type 1 pilus expression, the NU149 gadE UPEC strain was tested. The gadE mutant had higher fimE gene transcript levels, a higher frequency of Phase-OFF positioning of fimS, and hemagglutination titres that were lower in strain NU149 gadE cultured in low pH medium as compared to the wild-type bacteria. The data demonstrate that UPEC fim genes are regulated directly or indirectly by the GadE protein and this could have some future bearing on the ability to prevent urinary tract infections by acidifying the urine and shutting off fim gene expression.
Relationship between Low Muscle Strength, and Protein Intake: A Preliminary Study of Elderly Patients with Hip Fracture
Authors: Choi Kyung-A , Heu Eunseo , Nam Hyun-Cheul , Park Yongsoon , Kim Donghyun , Ha Yong-Chan
Published: March 2022

Background: The purpose of the present study was to assess the daily protein uptake and its relationship with sarcopenia, as defined by the Asian Working Group for Sarcopenia (AWGS), among elderly patients with hip fractures.Methods: Forty-seven elderly patients with hip fractures were enrolled in this retrospective observational study. The main outcome measures included protein uptake, muscle mass, and grip strength for sarcopenia in elderly patients. Sarcopenia was diagnosed according to AWGS. Wholebody densitometry was used to measure skeletal muscle mass, and muscle strength was evaluated using handgrip testing.Results: Of 47 patients with hip fractures (12 men and 35 women), 37 (79%) patients exhibited insufficient protein intake (range, 0.01-0.588 g/kg/day), and 10 (21%) patients exhibited excessive protein intake (range, 1.215-2.121 g/kg/day). The mean daily protein intake was 56.5 g (range, 7.2–136.0 g). Prevalence of low muscle strength (handgrip strength <18 kg in women and <26 kg in men) was detected in 13 (37%) women and 8 (67%) men (P=0.076). Sarcopenia (lower muscle mass and lower muscle strength) was detected in 9 (26%) women and 6 (50%) men (P=0.119). Although lower protein intake was marginally associated with sarcopenia (P=0.189), it was significantly associated with lower grip strength (P=0.042).Conclusions: The present study demonstrated that insufficient protein intake in elderly patients with hip fractures was common, and lower protein intake was significantly associated with lower muscle strength.
Food Security Moderates the Relationships of Muscle Mass with Metabolic Syndrome and Insulin Resistance
Authors: Lee Kayoung
Published: March 2022

Background: This study aimed to determine whether food security moderates the relationship of skeletal muscle mass with metabolic syndrome (MetS) and insulin resistance (IR).Methods: This study analyzed the data of 10,680 adults using the Korea National Health and Nutrition Examination Survey from 2008 to 2011. The food security reported by households, appendicular skeletal muscle mass (ASM) divided by body mass index (BMI) (ASM/BMI), weight (ASM/weight), or height squared (ASM/height2) as muscle mass indicators, MetS (defined as presence of at least 3 components of MetS), and IR (defined as sex-specific highest quintile of homeostatic model assessment for IR) were assessed. The association between the muscle mass indicators and food security as well as their interaction with MetS and IR was analyzed for all participants and each sex using complex sample logistic regression and general linear model analyses.Results: When the ASM/BMI increased by 0.1 kg/BMI, the odds for MetS and IR decreased by 36% and 29%, respectively, after adjusting for age, sex, education, economic level, smoking, alcohol consumption, physical activity, chronic diseases, and intake of fats and protein. There was a significant interaction between ASM/BMI and food security in their relationship with MetS and its components. In the low food security group, the inverse relationship of ASM/BMI with MetS and IR was stronger than in the food security group. These findings were more pronounced in men than in women, and similar findings were observed in the association with ASM/weight.Conclusions: The associations of skeletal muscle mass with MetS and IR may be influenced by household food security in Korean adults.
Prevalence and Risk Factors of T-Score Spine-Hip Discordance in Patients with Osteoporotic Vertebral Compression Fracture
Authors: Yoon Byung-Ho , Kang Ho Won , Kim Su Min , Koh Young Do
Published: March 2022

Background: T-score discordance between the spine and hip is commonly observed when dual energy X-ray absorptiometry (DXA) is used to diagnose osteoporosis. However, information is scarce regarding the prevalence and risk factors for this problem in Korea. This study evaluated the prevalence of major/minor discordance and associated risk factors in elderly Korean patients with osteoporotic vertebral compression fractures (OVCFs).Methods: This study included 200 patients (37 men, 163 women) treated for thoracic or lumbar compression fractures between January 2015 and August 2021. DXA was performed to examine T‐scores and determine the prevalence of discordance, defined as a difference between the T-score categories of the femur and spine in the same individual. The t-tests, χ2 tests, and regression analyses were used to assess the associated risk factors of T-score discordance among the subjects.Results: T-score concordance, minor discordance, and major discordance were observed in 137 (68.5%), 59 (29.5%), and 4 (2%) patients with OVCFs, respectively. The spinal T-score was lower than the femoral T-score in all major discordance and 81.3% (48/59) of minor discordant cases. Overall, the only factor related to T-score discordance was the age at fracture (odds ratio, -0.01; P=0.014).Conclusions: The results of this study showed that a significant number of subjects (31.5%) showed spine-hip discordance, even with a mean age in their 80s. More attention should be paid to the appropriate evaluation and management of elderly patients with OVCFs. Moreover, a longitudinal study is necessary to verify the clinical importance of T-score discordance in this population.
Heritability of cardiovascular health across three generations in South Africa: the Birth to Twenty-Plus cohort
Authors: Ware Lisa J , Maposa Innocent , Kolkenbeck-Ruh Andrea , Norris Shane , Soepnel Larske , Crouch Simone , Kagura Juliana , Naidoo Sanushka , Smith Wayne , Davies Justine
Published: March 2022

Objectives

Cardiovascular disease is increasing in many low-middle income countries, including those in Africa. To inform strategies for the prevention of cardiovascular disease in South Africa, we sought to determine the broad heritability of phenotypic markers of cardiovascular risk across three generations.

Design

A cross-sectional study conducted in a longitudinal family cohort.

Setting

Research unit within a tertiary hospital in a historically disadvantaged, large urban township of South Africa.

Participants

195 individuals from 65 biological families with all three generations including third generation children aged 4-10 years were recruited from the longest running intergenerational cohort study in Africa, the Birth to Twenty Plus cohort. All adults (grandparents and parents) were female, while children were male or female.

Primary and secondary outcome measures

The primary outcome was heritability of blood pressure (BP, brachial and central pressures). Secondary outcomes were heritability of arterial stiffness (pulse wave velocity), carotid intima media thickness (cIMT), and left ventricular mass indexed to body surface area (LVMI).

Results

While no significant intergenerational relationships of BP or arterial stiffness were found, there were significant relationships in LVMI across all three generations (p<0.04), and in cIMT between grandparents and parents (p=0.0166). Heritability estimates were 23-44% for cIMT and 21-39% for LVMI.

Conclusions

Structural indicators of vascular health, which are strong markers of future clinical cardiovascular outcomes transmit between generations within African families. Identification of these markers in parents may be useful to trigger assessments of preventable risk factors for cardiovascular disease in offspring.

Strengths

Intergenerational transmission was evaluated for a range of indicators of cardiovascular health within urban African families

The sample included biological family members from three generations

Heritability estimates were compared for three commonly used statistical methods.

Limitations

The sample size is a limitation with the random family statistical method used to increase the numbers of comparisons available.

Only maternal family members were included.
Identification of a Novel SARS-CoV-2 Delta-Omicron Recombinant Virus in the United States
Authors: Lacek Kristine A. , Rambo-Martin Benjamin L. , Batra Dhwani , Zheng Xiao-yu , Sakaguchi Hitoshi , Peacock Thomas , Keller Matthew , Wilson Malania M. , Sheth Mili , Davis Morgan L. , Borroughs Mark , Gerhart Jonathan , Hassell Norman , Shepard Samuel S. , Cook Peter W. , Lee Justin , Wentworth David E. , Barnes John R. , Kondor Rebecca , Paden Clinton R.
Published: March 2022

Recombination between SARS-CoV-2 virus variants can result in different viral properties (e.g., infectiousness or pathogenicity). In this report, we describe viruses with recombinant genomes containing signature mutations from Delta and Omicron variants. These genomes are the first evidence for a Delta-Omicron hybrid Spike protein in the United States.
Insulin sensitivity in mesolimbic pathways predicts and improves with weight loss in older dieters
Authors: Tiedemann Lena J , Meyhoefer Sebastian M , Francke Paul , Beck Judith , Buechel Christian , Brassen Stefanie
Published: March 2022

Central insulin is critically involved in the regulation of hedonic feeding. Insulin resistance in overweight has recently been shown to reduce the inhibitory function of insulin in the human brain, but how this relates to effective weight management is unclear, especially in the elderly, who are highly vulnerable to hyperinsulinemia and in whom neural target systems of insulin action undergo age-related changes. Here, fifty overweight, pre-diabetic elderly participated in a double-blind, placebo-controlled pharmacological longitudinal fMRI study before and after randomization to a 3-month caloric restriction or active waiting group. Our data show that treatment outcome in dieters can be predicted by baseline measures of individual intranasal insulin (INI) inhibition of value signals in the ventral tegmental area related to sweet food liking as well as, independently, by peripheral insulin sensitivity. At follow-up, both INI inhibition of hedonic value signals in the nucleus accumbens and whole-body insulin sensitivity improved with weight loss. These data highlight the critical role of central insulin function in mesolimbic systems for weight management in humans and directly demonstrate that neural insulin function can be improved by weight loss even in older age, which may be essential for preventing metabolic disorders in later life.
Associations between maternal complications during pregnancy and childhood asthma: a retrospective cohort study in southern China
Authors: Tang Jie , Ma Ying , Wu Yu , Jiao Ting , Guo Shuangshuang , Zhang Dongying , Yang Jiewen , Deng Nali , Liang Zhijiang , Wang Harry H.X. , Bao Wei , Liu Xiaoqing
Published: March 2022

Background
The associations between maternal complications during pregnancy and childhood asthma have rarely been investigated in low and middle-income countries. We aimed to investigate the associations among the southern Chinese population, and to determine whether the associations were mediated through preterm birth, cesarean delivery, low birth weight and non-breasting feeding in the first 6 months or modified by child’s lifestyles (smoking, body mass index(BMI), and sleep duration).
Methods
We conducted a retrospective cohort study of 208,190 children in Guangzhou, China. Information on maternal gestational hypertension, gestational diabetes, gestational anemia, and hepatitis B during pregnancy was extracted from medical records. Ever diagnosis of asthma of the children was obtained by questionnaire. We used binomial logistic regression models to estimate the adjusted odds ratios (aORs) and 95% confidential interval (CI) for childhood asthma. We conducted mediation analyses to estimate the indirect effects of gestational complications on childhood asthma mediated through preterm birth, cesarean delivery, low birth weight, and non-breastfeeding in the first 6 months.
Findings
The overall prevalence of ever diagnosed asthma was 1.3%. Gestational hypertension, gestational diabetes, gestational anemia, or hepatitis B during pregnancy was positively associated with ever diagnosed childhood asthma, with the aOR of 1.66(95%CI 1.31-2.10), 1.68(95%CI 1.40-2.02), 1.69(95%CI 1.49-1.91) and 1.54(95%CI 1.13-2.08), respectively. A stronger association was observed for 2 or more gestational complications (aOR= 2.34, 95%CI 1.71-3.23) than 1 gestational complication (aOR=1.80, 95%CI 1.62-1.99). The associations between maternal complications and childhood asthma did not differ by child’s smoking, BMI, or sleep duration, except that the aOR for maternal gestational hypertension was significantly higher in children who were active smoker (aOR=5.68, 95%CI 2.09-15.42) than those who were non-smoker (aOR=1.56, 95%CI 1.21-2.00). A small proportion of the associations were mediated through preterm birth, cesarean delivery, low birth weight, and non-breastfeeding in the first 6 months.
Interpretation
Gestational hypertension, diabetes, anemia, or hepatitis B during pregnancy was significantly associated with childhood asthma in the southern Chinese population, and the associations were partially explained by the mediation effects of cesarean delivery, preterm birth, low birthweight and non-breastfeeding in the first 6 months.
Parental income gradients in child and adolescent mortality: Norwegian trends over half a century
Authors: Evensen Miriam , Klitkou Søren , Tollånes Mette , Juliusson Petur B , Kravdal Øystein
Published: March 2022

Background

Child mortality declined rapidly the last century in many high-income countries. However, little is known about the socioeconomic differences in this decline, and whether these vary across causes of death.

Methods

We use register data including all Norwegian births between 1968 to 2010 (2.1 million), and analyse how all-cause and cause-specific child (0-5) and adolescent mortality (6-21) vary with relative parental income the year before the birth

Results

Child all-cause mortality decreased with increasing parental relative income within all birth cohorts. Among children aged 0-5, the socioeconomic gradient for all-cause, accidental deaths, sudden infant death syndrome and perinatal factors declined over the periode, while there was no systematic decline related to congenital malformations. Among children 6-21, the gradient did not weaken similarly, although there were indications of declines in the socioeconomic gradient related to all-cause deaths, accidents, and suicides. While the absolute differences in mortality declined over time, the relative differences remained stable.

Conclusion

There has been a large reduction in child mortality in all socioeconomic groups across 50 years for all-cause and most cause-specific mortality groups. However, children of parents in the lowest part of the income distribution still have an elevated mortality, and the relative differences have not always been declining.
Enabling automated and reproducible spatially resolved transcriptomics at scale
Authors: Stenbeck Linnea , Taborsak-Lines Fanny , Giacomello Stefania
Published: March 2022

Tissue spatial information is an essential component to reach a holistic overview of gene expression mechanisms. The sequencing-based Spatial transcriptomics approach allows to spatially barcode the whole transcriptome of tissue sections using microarray glass slides. However, manual preparation of high-quality tissue sequencing libraries is time-consuming and subjected to technical variability. Here, we present an automated adaptation of the 10x Genomics Visium library construction on the widely used Agilent Bravo Liquid Handling Platform. Compared to the manual Visium library preparation, our automated approach reduces hands-on time by over 80% and provides higher throughput and robustness. Our automated Visium library preparation protocol provides a new strategy to standardize spatially resolved transcriptomics analysis of tissues at scale.
A conserved mechanism regulates reversible amyloids via pH-sensing regions
Authors: Cereghetti Gea , Kissling Vera Maria , Koch Lisa Maria , Arm Alexandra , Afanasyev Pavel , Linsenmeier Miriam , Eichmann Cédric , Zhou Jiangtao , Cao Yiping , Pfizenmaier Dorota Maria , Kroschwald Sonja , Wiegand Thomas , Cadalbert Riccardo , Böhringer Daniel , Mezzenga Raffaele , Arosio Paolo , Riek Roland , Peter Matthias
Published: March 2022

Amyloids were long viewed as irreversible, pathological aggregates, often associated with neurodegenerative diseases1. However, recent insights challenge this view, providing evidence that reversible amyloids can form upon stress conditions and fulfil crucial cellular functions2. Yet, the molecular mechanisms regulating functional amyloids and the differences to their pathological counterparts remain poorly understood. Here we investigate the conserved principles of amyloid reversibility by studying the essential metabolic enzyme pyruvate kinase (PK) in yeast and human cells. We demonstrate that PK forms stress-dependent reversible amyloids through a pH-sensitive amyloid core. Stress- induced cytosolic acidification promotes aggregate formation via protonation of specific glutamate (in yeast) or histidine (in human) residues within the amyloid core. Our work thus unravels a conserved and potentially widespread mechanism underlying amyloid functionality and reversibility, fine-tuned to the respective physiological cellular pH range.
Multi-modal Imaging of Disease Progression in TH-MYCN Mouse Models of Neuroblastoma
Authors: Badachhape Andrew A. , Tao Ling , Joshi Sanshuv , Starosolski Zbigniew , Devkota Laxman , Sarkar Poonam , Bhandari Prajwal , Annapragada Ananth V. , Barbieri Eveline , Ghaghada Ketan B.
Published: March 2022

MYCN is a major driver for neuroblastoma (NB) and the tyrosine hydroxylase (TH)-MYCN transgenic mouse model is extensively used for preclinical NB studies. However, spatio-temporal NB progression in the TH-MYCN model has not been studied, and questions remain about the value of implanted models as a surrogate for transgenic mice. In this work, we used magnetic resonance imaging (MRI) to study tumor progression and nanoparticle contrast-enhanced computed tomography (n-CECT) to assess tumor vascular architecture in TH-MYCN transgenic mice (2–7 weeks of age) and TH-MYCN+/+-derived orthotopic allograft and syngeneic mice (2–5 weeks post-tumor implantation). Tumors in TH-MYCN transgenic mice became evident in the abdominal paraspinal region at week 5. A delayed thoracic paraspinal mass became evident at week 6 and most mice succumbed by week 7. In allograft and syngeneic mice, single mass tumor growth was restricted to the peritoneal cavity. N-CECT revealed a predominantly microvascular network in TH-MYCN tumors while implanted tumors exhibited heterogeneous and tortuous vessels. N-CECT quantitative analysis demonstrated high vascularity (tumor fractional blood volume ~ 0.12) in all models. Multi-modal imaging of TH-MYCN transgenic and implanted models revealed differences in growth patterns and vascular architecture that should be considered in designing preclinical studies.
Triple Notch/Tgfβ/FoxO1 blockade converts multiple intestinal sub-lineages into β-like cells and lowers glycemia in diabetic animals
Authors: Du Wen , Wang Junqiang , Kuo Taiyi , Wang Liheng , McKimpson Wendy M. , Son Jinsook , Watanabe Hitoshi , Kitamoto Takumi , Lee YunKyoung , Ratner Lloyd E. , McCune Kasi , Chen Ya-Wen , Grubbs Brendan H. , Thornton Matthew E. , Fan Jason , Sultana Nishat , Diaz Bryan , Balasubramanian Iyshwarya , Gao Nan , Belvedere Sandro , Accili Domenico
Published: March 2022

Insulin is the essential treatment of Type 1 (T1D) and is often used in Type 2 Diabetes. For nearly five decades, efforts have been focused on replenishing β-cells in T1D patients as a more durable treatment. Gut endocrine cells can be converted into insulin-producing cells, but their numbers are limited. In this study we report that insulin-immunoreactive cells with Paneth/goblet cell features are present in human fetal intestine, in addition to enteroendocrine cells. Accordingly, lineage tracing experiments show that, besides enterochromaffin cells, the Paneth/goblet lineage can undergo conversion to the insulin lineage upon genetic or pharmacologic Foxo1 ablation in mice. We leveraged these data to design a screening platform in organoids to accurately quantitate β-like cell reprogramming and fine-tune a combination treatment to increase the efficiency of the conversion process by expanding the intestinal secretory lineage. We identified a triple blockade of FoxO1, Notch, and Tgfβ that, when tested in insulin-deficient diabetic animals resulted in a near-normalization of glucose levels, associated with the appearance of gut insulin-producing cells. The findings illustrate a therapeutic approach to replace insulin treatment in diabetes.