Effectiveness of a Home-Based Eccentric-Exercise Program on the Torque-Angle Relationship of the Shoulder External Rotators: A Pilot Study

Context: The role of the rotator cuff is to provide dynamic stability to the glenohumeral joint. Human and animal studies have identified sarcomerogenesis as an outcome of eccentric training indicated by more torque generation with the muscle in a lengthened position. Objective: The authors hypothesized that a home-based eccentric-exercise program could increase the shoulder external rotators’ eccentric strength at terminal internal rotation (IR). Design: Prospective case series. Setting: Clinical laboratory and home exercising. Participants: 10 healthy subjects (age 30 ± 10 y). Intervention: All participants performed 2 eccentric exercises targeting the posterior shoulder for 6 wk using a home-based intervention program using side-lying external rotation (ER) and horizontal abduction. Main Outcome Measures: Dynamic eccentric shoulder strength measured at 60°/s through a 100° arc divided into 4 equal 25° arcs (ER 50–25°, ER 25–0°, IR 0–25°, IR 25–50°) to measure angular impulse to represent the work performed. In addition, isometric shoulder ER was measured at 5 points throughout the arc of motion (45° IR, 30° IR, 15° IR, 0°, and 15° ER). Comparison of isometric and dynamic strength from pre- to posttesting was evaluated with a repeated-measure ANOVA using time and arc or positions as within factors. Results: The isometric force measures revealed no significant differences between the 5 positions (P = .56). Analysis of the dynamic eccentric data revealed a significant difference between arcs (P = .02). The percentage-change score of the arc of IR 25–50° was found to be significantly greater than that of the arc of IR 0–25° (P = .007). Conclusion: After eccentric training the only arc of motion that had a positive improvement in the capacity to absorb eccentric loads was the arc of motion that represented eccentric contractions at the longest muscle length

Effectiveness of a Home-Based Eccentric-Exercise Program on the Torque-Angle Relationship of the Shoulder External Rotators: A Pilot Study

Context: The role of the rotator cuff is to provide dynamic stability to the glenohumeral joint. Human and animal studies have identified sarcomerogenesis as an outcome of eccentric training indicated by more torque generation with the muscle in a lengthened position. Objective: The authors hypothesized that a home-based eccentric-exercise program could increase the shoulder external rotators’ eccentric strength at terminal internal rotation (IR). Design: Prospective case series. Setting: Clinical laboratory and home exercising. Participants: 10 healthy subjects (age 30 ± 10 y). Intervention: All participants performed 2 eccentric exercises targeting the posterior shoulder for 6 wk using a home-based intervention program using side-lying external rotation (ER) and horizontal abduction. Main Outcome Measures: Dynamic eccentric shoulder strength measured at 60°/s through a 100° arc divided into 4 equal 25° arcs (ER 50–25°, ER 25–0°, IR 0–25°, IR 25–50°) to measure angular impulse to represent the work performed. In addition, isometric shoulder ER was measured at 5 points throughout the arc of motion (45° IR, 30° IR, 15° IR, 0°, and 15° ER). Comparison of isometric and dynamic strength from pre- to posttesting was evaluated with a repeated-measure ANOVA using time and arc or positions as within factors. Results: The isometric force measures revealed no significant differences between the 5 positions (P = .56). Analysis of the dynamic eccentric data revealed a significant difference between arcs (P = .02). The percentage-change score of the arc of IR 25–50° was found to be significantly greater than that of the arc of IR 0–25° (P = .007). Conclusion: After eccentric training the only arc of motion that had a positive improvement in the capacity to absorb eccentric loads was the arc of motion that represented eccentric contractions at the longest muscle length

New Methods in Tissue Engineering: Improved Models for Viral Infection

New insights in the study of virus and host biology in the context of viral infection are made possible by the development of model systems that faithfully recapitulate the in vivo viral life cycle. Standard tissue culture models lack critical emergent properties driven by cellular organization and in vivo–like function, whereas animal models suffer from limited susceptibility to relevant human viruses and make it difficult to perform detailed molecular manipulation and analysis. Tissue engineering techniques may enable virologists to create infection models that combine the facile manipulation and readouts of tissue culture with the virus-relevant complexity of animal models. Here, we review the state of the art in tissue engineering and describe how tissue engineering techniques may alleviate some common shortcomings of existing models of viral infection, with a particular emphasis on hepatotropic viruses. We then discuss possible future applications of tissue engineering to virology, including current challenges and potential solutions.Hertz Foundation (Fellowship)National Science Foundation (U.S.). Graduate Research FellowshipNational Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant DK085713)Skolkovo Institute of Science and Technology (Grant 022423-003

Interferon Lambda Alleles Predict Innate Antiviral Immune Responses and Hepatitis C Virus Permissiveness

SummaryHepatitis C virus (HCV) infection can result in viral chronicity or clearance. Although host genetics and particularly genetic variation in the interferon lambda (IFNL) locus are associated with spontaneous HCV clearance and treatment success, the mechanisms guiding these clinical outcomes remain unknown. Using a laser capture microdissection-driven unbiased systems virology approach, we isolated and transcriptionally profiled HCV-infected and adjacent primary human hepatocytes (PHHs) approaching single-cell resolution. An innate antiviral immune signature dominated the transcriptional response but differed in magnitude and diversity between HCV-infected and adjacent cells. Molecular signatures associated with more effective antiviral control were determined by comparing donors with high and low infection frequencies. Cells from donors with clinically unfavorable IFNL genotypes were infected at a greater frequency and exhibited dampened antiviral and cell death responses. These data suggest that early virus-host interactions, particularly host genetics and induction of innate immunity, critically determine the outcome of HCV infection

Complete replication of hepatitis C virus in cell culture.

Many aspects of the hepatitis C virus (HCV) life cycle have not been reproduced in cell culture, which has slowed research progress on this important human pathogen. Here, we describe a full-length HCV genome that replicates and produces virus particles that are infectious in cell culture (HCVcc). Replication of HCVcc was robust, producing nearly 10(5) infectious units per milliliter within 48 hours. Virus particles were filterable and neutralized with a monoclonal antibody against the viral glycoprotein E2. Viral entry was dependent on cellular expression of a putative HCV receptor, CD81. HCVcc replication was inhibited by interferon-alpha and by several HCV-specific antiviral compounds, suggesting that this in vitro system will aid in the search for improved antivirals

The upper airway response to pollen is enhanced by exposure to combustion particulates: a pilot human experimental challenge study.

Although human experimental studies have shown that gaseous pollutants enhance the inflammatory response to allergens, human data on whether combustion particulates enhance the inflammatory response to allergen are limited. Therefore, we conducted a human experimental study to investigate whether combustion particulates enhance the inflammatory response to aeroallergens. "Enhancement" refers to a greater-than-additive response when combustion particulates are delivered with allergen, compared with the responses when particulates and allergen are delivered alone. Eight subjects, five atopic and three nonatopic, participated in three randomized exposure-challenge sessions at least 2 weeks apart (i.e., clean air followed by allergen, particles followed by no allergen, or particles followed by allergen). Each session consisted of nasal exposure to combustion particles (target concentration of 1.0 mg/m3) or clean air for 1 hr, followed 3 hr later by challenge with whole pollen grains or placebo. Nasal lavage was performed immediately before particle or clean air exposure, immediately after exposure, and 4, 18 and 42 hr after pollen challenge. Cell counts, differentials, and measurement of cytokines were performed on each nasal lavage. In atopic but not in nonatopic subjects, when allergen was preceded by particulates, there was a significant enhancement immediately after pollen challenge in nasal lavage leukocytes and neutrophils (29.7 X 10(3) cells/mL and 25.4 X 10(3) cells/mL, respectively). This represents a 143% and 130% enhancement, respectively. The enhanced response for interleukin-4 was 3.23 pg/mL (p = 0.06), a 395% enhancement. In atopic subjects there was evidence of an enhanced response when particulates, as compared to clean air, preceded the allergen challenge

The Upper Airway Response to Pollen is Enhanced by Exposure to Combustion Particulates: A Pilot Human Experimental Challenge Study.

Although human experimental studies have shown that gaseous pollutants enhance the inflammatory response to allergens, human data on whether combustion particulates enhance the inflammatory response to allergen are limited. Therefore, we conducted a human experimental study to investigate whether combustion particulates enhance the inflammatory response to aeroallergens. "Enhancement" refers to a greater-than-additive response when combustion particulates are delivered with allergen, compared with the responses when particulates and allergen are delivered alone. Eight subjects, five atopic and three nonatopic, participated in three randomized exposure-challenge sessions at least 2 weeks apart (i.e., clean air followed by allergen, particles followed by no allergen, or particles followed by allergen). Each session consisted of nasal exposure to combustion particles (target concentration of 1.0 mg/m$^3$) or clean air for 1 hr, followed 3 hr later by challenge with whole pollen grains or placebo. Nasal lavage was performed immediately before particle or clean air exposure, immediately after exposure, and 4, 18 and 42 hr after pollen challenge. Cell counts, differentials, and measurement of cytokines were performed on each nasal lavage. In atopic but not in nonatopic subjects, when allergen was preceded by particulates, there was a significant enhancement immediately after pollen challenge in nasal lavage leukocytes and neutrophils (29.7 X 10$^3$ cells/mL and 25.4 X 10$^3$ cells/mL, respectively). This represents a 143% and 130% enhancement, respectively. The enhanced response for interleukin-4 was 3.23 pg/mL (p = 0.06), a 395% enhancement. In atopic subjects there was evidence of an enhanced response when particulates, as compared to clean air, preceded the allergen challenge

Oncologic outcomes and prognostic impact of urothelial recurrences in patients undergoing segmental and total ureterectomy for upper tract urothelial carcinoma

INTRODUCTION: We evaluated the impact of urothelial recurrences in a cohort of patients undergoing segmental (SU) and total ureterectomy (TU) as an alternative to nephroureterectomy (NU) for upper tract urothelial carcinoma. METHODS: Between 1999 and 2012, patients who underwent SU, TU and NU for treatment of upper tract urothelial carcinoma were evaluated. Demographic, surgical, pathologic and oncologic data were collected. Recurrence-free (RFS) and disease-specific survival (DSS) were analyzed using Kaplan-Meier and multivariable Cox methods. RESULTS: A total 141 patients were evaluated, 35 underwent SU, 10 TU and 96 NU. Patients who underwent TU were more likely to have bilateral disease (p < 0.01), solitary kidney (p < 0.01), and multifocal disease (p = 0.01). Organ-confined (p < 0.01) and low-grade disease (p < 0.01) were more common in the TU and SU groups compared with NU. At a median follow-up of 56.9 months (range: 0.2-181.1) disease relapse occurred in 88 (55.3%) patients. Localized recurrence occurred in 31.1% of SU/TU group compared to 27.1% (p = 0.62) of the NU group. Neither total nor segmental ureterectomy demonstrated significantly worse RFS (p = 0.26 and p = 0.81), CSS (p = 0.96 and p = 0.52) or overall survival (p = 0.59 and p = 0.55) compared with complete NU. Localized urothelial recurrence did not confer increased risk of cancer-specific (p = 0.73) or overall mortality (p = 0.39). The paper's most important limitations include its retrospective nature and its relatively small number of patients. CONCLUSION: No significant survival differences were demonstrated between surgical approaches for upper tract urothelial cancer. Localized urothelial recurrence after surgical treatment for upper tract urothelial cancer does not affect mortality in this population. TU with ileal-substitution may provide an alternative option for patients with extensive ureteral disease and poor renal function

A Tight Upper Limit on Oscillations in the Ap star Epsilon Ursae Majoris from WIRE Photometry

Observations of Epsilon UMa obtained with the star tracker on the Wide Field Infrared Explorer (WIRE) satellite during a month in mid-2000 are analyzed. This is one of the most precise photometry of an Ap star. The amplitude spectrum is used to set an upper limit of 75 parts per million for the amplitude of stellar pulsations in this star unless it accidentally oscillates with a single mode at the satellite orbit, its harmonics or their one day aliases. This is the tightest limit put on the amplitude of oscillations in an Ap star. As the rotation period of Epsilon UMa is relatively short (5.1 d), it cannot be argued that the observations were made at a wrong rotational phase. Our results thus support the idea that some Ap stars do not pulsate at all.Comment: 4 pages, 4 figures, 2 style files, accepted for publication in ApJ

Evaluation of a male-specific psychotherapeutic program for major depressive disorder compared to cognitive behavioral therapy and waitlist: study protocol for a six-arm randomized clinical superiority trial examining depressed eugonadal and hypogonadal men receiving testosterone

BACKGROUND: Treatment of major depressive disorder (MDD) in men is complicated by the endorsement of traditional masculinity ideologies (TMI) often leading to reluctance toward psychotherapy, therapy interfering processes, or premature termination. In addition, it has been shown that men with MDD have a significantly increased risk of being hypogonadal (e.g., total testosterone levels <12.1 nmoL/L). Therefore, it is recommended to examine depressed men with regard to their testosterone status and if hypogonadism is present to combine psychotherapy with testosterone treatment (TT). AIM: This project aims to evaluate a male-specific psychotherapeutic program (MSPP) for MDD in depressed eugonadal and hypogonadal men receiving testosterone in comparison to a standard cognitive behavioral therapy (CBT) for MDD and a Waitlist. METHODS: The study presents a 2×3 factorial study design. In total, 144 men aged between 25 and 50 will be stratified by testosterone status (eugonadal/hypogonadal) and then randomized into one of the three conditions (MSPP, CBT, or Waitlist). Additionally, a healthy control group of 100 men will be recruited, which will undergo only baseline assessments. Both standardized psychotherapy programs will encompass 18 sessions delivered in a weekly manner. Aligned with the TT-related medical visits of the 72 hypogonadal men, all participants will be followed up with clinical assessments and bio sampling at weeks 0, 6, 15, 24, and 36. EXPECTED RESULTS: Compared to Waitlist control groups, treatment groups are expected to be more effective and efficacious (depression score reduction of ≥50%) at week 24 and at the follow-up at week 36. The MSPP is expected to show higher effectiveness and efficacy for depressive symptoms and higher acceptability (lower dropout rate) as compared to CBT. DISCUSSION: This study represents the first attempt to test a male-specific psychotherapy for MDD in a single-setting compared to standard CBT and a Waitlist control condition using randomized clinical trial methodology. In addition, the potential positive adjunct effect of psychotherapy to TT in reducing depressive burden and improving quality of life in hypogonadal depressed men represents a neglected research area and might introduce new hypogonadism screening procedures in depressed men and combined treatment approaches for depressed men suffering from hypogonadism. Limitations are the rigorous inclusion and exclusion criteria, which limit the generalizability of the study results to first episode treatment naïve depressed men. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT05435222