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Background: SMS text messaging- and internet-based self-reporting systems can supplement existing vaccine safety surveillance systems, but real-world participation patterns have not been assessed at scale., Objective: This study aimed to describe the participation rates of a new SMS text messaging- and internet-based self-reporting system called the Kaiser Permanente Side Effect Monitor (KPSEM) within a large integrated health care system., Methods: We conducted a prospective cohort study of Kaiser Permanente Southern California (KPSC) patients receiving a COVID-19 vaccination from April 23, 2021, to July 31, 2023. Patients received invitations through flyers, SMS text messages, emails, or patient health care portals. After consenting, patients received regular surveys to assess adverse events up to 5 weeks after each dose. Linkage with medical records provided demographic and clinical data. In this study, we describe KPSEM participation rates, defined as providing consent and completing at least 1 survey within 35 days of COVID-19 vaccination., Results: Approximately, 8% (164,636/2,091,975) of all vaccinated patients provided consent and completed at least 1 survey within 35 days. The lowest participation rates were observed for parents of children aged 12-17 years (1349/152,928, 0.9% participation rate), and the highest participation was observed among older adults aged 61-70 years (39,844/329,487, 12.1%). Persons of non-Hispanic White race were more likely to participate compared with other races and ethnicities (13.1% vs 3.9%-7.5%, respectively; P<.001). In addition, patients residing in areas with a higher neighborhood deprivation index were less likely to participate (5.1%, 16,503/323,122 vs 10.8%, 38,084/352,939 in the highest vs lowest deprivation quintiles, respectively; P<.001). Invitations through the individual's Kaiser Permanente health care portal account and by SMS text message were associated with the highest participation rate (19.2%, 70,248/366,377 and 10.5%, 96,169/914,793, respectively), followed by email (19,464/396,912, 4.9%) and then QR codes on flyers (25,882/2,091,975, 1.2%). SMS text messaging-based surveys demonstrated the highest sustained daily response rates compared with internet-based surveys., Conclusions: This real-world prospective study demonstrated that a novel digital vaccine safety self-reporting system implemented through an integrated health care system can achieve high participation rates. Linkage with participants' electronic health records is another unique benefit of this surveillance system. We also identified lower participation among selected vulnerable populations, which may have implications when interpreting data collected from similar digital systems., (©Debbie E Malden, Julianne Gee, Sungching Glenn, Zhuoxin Li, Denison S Ryan, Zheng Gu, Cassandra Bezi, Sunhea Kim, Amelia Jazwa, Michael M McNeil, Eric S Weintraub, Sara Y Tartof. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 11.10.2024.)

Importance: People with HIV (PWH) may be at increased risk for severe outcomes with COVID-19 illness compared with people without HIV. Little is known about COVID-19 vaccination coverage and factors associated with primary series completion among PWH., Objectives: To evaluate COVID-19 vaccination coverage among PWH and examine sociodemographic, clinical, and community-level factors associated with completion of the primary series and an additional primary dose., Design, Setting, and Participants: This retrospective cohort study used electronic health record data to assess COVID-19 vaccination information from December 14, 2020, through April 30, 2022, from 8 health care organizations of the Vaccine Safety Datalink project in the US. Participants were adults diagnosed with HIV on or before December 14, 2020, enrolled in a participating site., Main Outcomes and Measures: The percentage of PWH with at least 1 dose of COVID-19 vaccine and PWH who completed the COVID-19 vaccine primary series by December 31, 2021, and an additional primary dose by April 30, 2022. Rate ratios (RR) and 95% CIs were estimated using Poisson regression models for factors associated with completing the COVID-19 vaccine primary series and receiving an additional primary dose., Results: Among 22 058 adult PWH (mean [SD] age, 52.1 [13.3] years; 88.8% male), 90.5% completed the primary series by December 31, 2021. Among 18 374 eligible PWH who completed the primary series by August 12, 2021, 15 982 (87.0%) received an additional primary dose, and 4318 (23.5%) received a booster dose by April 30, 2022. Receipt of influenza vaccines in the last 2 years was associated with completion of the primary series (RR, 1.17; 95% CI, 1.15-1.20) and an additional primary dose (RR, 1.61; 95% CI, 1.54-1.69). PWH with uncontrolled viremia (HIV viral load ≥200 copies/mL) (eg, RR, 0.90 [95% CI, 0.85-0.95] for viral load 200-10 000 copies/mL vs undetected or <200 copies/mL for completing the primary series) and Medicaid insurance (eg, RR, 0.89 [95% CI, 0.87-0.90] for completing the primary series) were less likely to be fully vaccinated. By contrast, greater outpatient utilization (eg, RR, 1.07 [95% CI, 1.05-1.09] for ≥7 vs 0 visits for primary series completion) and residence in counties with higher COVID-19 vaccine coverage (eg, RR, 1.06 [95% CI, 1.03-1.08] for fourth vs first quartiles for primary series completion) were associated with primary series and additional dose completion (RRs ranging from 1.01 to 1.21)., Conclusions and Relevance: Findings from this cohort study suggest that, while COVID-19 vaccination coverage was high among PWH, outreach efforts should focus on those who did not complete vaccine series and those who have uncontrolled viremia.

COVID-19 vaccinations protect against severe illness and death, but associations with post-COVID conditions (PCC) are less clear. We aimed to evaluate the association between prior COVID-19 vaccination and new-onset PCC among individuals with SARS-CoV-2 infection across eight large healthcare systems in the United States. This retrospective matched cohort study used electronic health records (EHR) from patients with SARS-CoV-2 positive tests during March 2021-February 2022. Vaccinated and unvaccinated COVID-19 cases were matched on location, test date, severity of acute infection, age, and sex. Vaccination status was ascertained using EHR and integrated data on externally administered vaccines. Adjusted relative risks (RRs) were obtained from Poisson regression. PCC was defined as a new diagnosis in one of 13 PCC categories 30 days to 6 months following a positive SARS-CoV-2 test. The study included 161,531 vaccinated COVID-19 cases and 161,531 matched unvaccinated cases. Compared to unvaccinated cases, vaccinated cases had a similar or lower risk of all PCC categories except mental health disorders (RR: 1.06, 95% CI: 1.02-1.10). Vaccination was associated with ≥10% lower risk of sensory (RR: 0.90, 0.86-0.95), circulatory (RR: 0.88, 0.83-0.94), blood and hematologic (RR: 0.79, 0.71-0.89), skin and subcutaneous (RR: 0.69, 0.66-0.72), and non-specific COVID-19 related disorders (RR: 0.53, 0.51-0.56). In general, associations were stronger at younger ages but mostly persisted regardless of SARS-CoV-2 variant period, receipt of ≥3 vs. 1-2 vaccine doses, or time since vaccination. Pre-infection vaccination was associated with reduced risk of several PCC outcomes and hence may decrease the long-term consequences of COVID-19., (© 2024. The Author(s).)

Background: Understanding the long-term impact of the COVID-19 pandemic on health care utilization is important to health care organizations and policy makers for strategic planning, as well as to researchers when designing studies that use observational electronic health record data during the pandemic period., Objective: This study aimed to evaluate the changes in health care utilization across all care settings among a large, diverse, and insured population in the United States during the COVID-19 pandemic., Methods: We conducted a retrospective cohort study within 8 health care organizations participating in the Vaccine Safety Datalink Project using electronic health record data from members of all ages from January 1, 2017, to December 31, 2021. The visit rates per person-year were calculated monthly during the study period for 4 health care settings combined as well as by inpatient, emergency department (ED), outpatient, and telehealth settings, both among all members and members without COVID-19. Difference-in-difference analysis and interrupted time series analysis were performed to assess the changes in visit rates from the prepandemic period (January 2017 to February 2020) to the early pandemic period (April-December 2020) and the later pandemic period (July-December 2021), respectively. An exploratory analysis was also conducted to assess trends through June 2023 at one of the largest sites, Kaiser Permanente Southern California., Results: The study included more than 11 million members from 2017 to 2021. Compared with the prepandemic period, we found reductions in visit rates during the early pandemic period for all in-person care settings. During the later pandemic period, overall use reached 8.36 visits per person-year, exceeding the prepandemic level of 7.49 visits per person-year in 2019 (adjusted percent change 5.1%, 95% CI 0.6%-9.9%); inpatient and ED visits returned to prepandemic levels among all members, although they remained low at 0.095 and 0.241 visits per person-year, indicating a 7.5% and 8% decrease compared to pre-pandemic levels among members without COVID-19, respectively. Telehealth visits, which were approximately 42% of the volume of outpatient visits during the later pandemic period, were increased by 97.5% (95% CI 86.0%-109.7%) from 0.865 visits per person-year in 2019 to 2.35 visits per person-year in the later pandemic period. The trends in Kaiser Permanente Southern California were similar to those of the entire study population. Visit rates from January 2022 to June 2023 were stable and appeared to be a continuation of the use levels observed at the end of 2021., Conclusions: Telehealth services became a mainstay of the health care system during the late COVID-19 pandemic period. Inpatient and ED visits returned to prepandemic levels, although they remained low among members without evidence of COVID-19. Our findings provide valuable information for strategic resource allocation for postpandemic patient care and for designing observational studies involving the pandemic period., (©Lei Qian, Lina S Sy, Vennis Hong, Sungching C Glenn, Denison S Ryan, Jennifer C Nelson, Simon J Hambidge, Bradley Crane, Ousseny Zerbo, Malini B DeSilva, Jason M Glanz, James G Donahue, Elizabeth Liles, Jonathan Duffy, Stanley Xu. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 23.01.2024.)

Background: Shoulder injury related to vaccine administration (SIRVA) accounts for more than half of all claims received by the National Vaccine Injury Compensation Program. However, due to the difficulty of finding SIRVA cases in large health care databases, population-based studies are scarce., Objective: The goal of the research was to develop a natural language processing (NLP) method to identify SIRVA cases from clinical notes., Methods: We conducted the study among members of a large integrated health care organization who were vaccinated between April 1, 2016, and December 31, 2017, and had subsequent diagnosis codes indicative of shoulder injury. Based on a training data set with a chart review reference standard of 164 cases, we developed an NLP algorithm to extract shoulder disorder information, including prior vaccination, anatomic location, temporality and causality. The algorithm identified 3 groups of positive SIRVA cases (definite, probable, and possible) based on the strength of evidence. We compared NLP results to a chart review reference standard of 100 vaccinated cases. We then applied the final automated NLP algorithm to a broader cohort of vaccinated persons with a shoulder injury diagnosis code and performed manual chart confirmation on a random sample of NLP-identified definite cases and all NLP-identified probable and possible cases., Results: In the validation sample, the NLP algorithm had 100% accuracy for identifying 4 SIRVA cases and 96 cases without SIRVA. In the broader cohort of 53,585 vaccinations, the NLP algorithm identified 291 definite, 124 probable, and 52 possible SIRVA cases. The chart-confirmation rates for these groups were 95.5% (278/291), 67.7% (84/124), and 17.3% (9/52), respectively., Conclusions: The algorithm performed with high sensitivity and reasonable specificity in identifying positive SIRVA cases. The NLP algorithm can potentially be used in future population-based studies to identify this rare adverse event, avoiding labor-intensive chart review validation., (©Chengyi Zheng, Jonathan Duffy, In-Lu Amy Liu, Lina S Sy, Ronald A Navarro, Sunhea S Kim, Denison S Ryan, Wansu Chen, Lei Qian, Cheryl Mercado, Steven J Jacobsen. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 24.05.2022.)

Purpose: To determine the rates and types of open-globe wounds in soldiers admitted to Walter Reed Army Medical Center from 2001 to 2011 after sustaining combat injuries., Methods: Data were collected in the Walter Reed Ocular Trauma Database. Inclusion criteria were patients who suffered open-globe injuries. Open-globe injuries were classified by type of wound: corneal, corneo-scleral or scleral, or type of open-globe injury: perforating, rupture, penetrating or intraocular foreign body. The primary analysis assessed the effect on final visual acuity (VA) and the risk of enucleation., Results: In this study, 285 (32.02%) open-globe injuries were recorded in 890 eyes in the data set. Corneal wounds were noted in 127 (44.56%) eyes, corneo-scleral wounds in 78 (27.37%) and scleral wounds in 129 (45.26%) eyes. The involvement of both the corneal and sclera was associated with poorer visual outcome (BCVA < 20/200) compared to injuries with an injury confined to either the cornea or scleral alone (p = 0.038). At a wound length of greater than approximately 14 mm, patients had 75% chance of having a poor final VA. Enucleation was performed in 64 (22.46%) eyes of patients with wounds. The type of wound was not found to be predictive of enucleation in multivariate analysis, but rather the type of open-globe injury was predictive. Perforating (OR: 1.58, 95% CI: 1.43-1.72) and globe rupture injuries (OR: 1.49, 95% CI: 1.33-1.66) were more likely to undergo enucleation., Conclusions: Open-globe injuries occur frequently in combat ocular trauma. Poor final VA was noted most with corneo-scleral wounds with approximately 50% of patients having a final VA less than 20/200., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

By September 21, 2021, an estimated 182 million persons in the United States were fully vaccinated against COVID-19.* Clinical trials indicate that Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen (Johnson & Johnson; Ad.26.COV2.S) vaccines are effective and generally well tolerated (1-3). However, daily vaccination rates have declined approximately 78% since April 13, 2021 † ; vaccine safety concerns have contributed to vaccine hesitancy (4). A cohort study of 19,625 nursing home residents found that those who received an mRNA vaccine (Pfizer-BioNTech or Moderna) had lower all-cause mortality than did unvaccinated residents (5), but no studies comparing mortality rates within the general population of vaccinated and unvaccinated persons have been conducted. To assess mortality not associated with COVID-19 (non-COVID-19 mortality) after COVID-19 vaccination in a general population setting, a cohort study was conducted during December 2020-July 2021 among approximately 11 million persons enrolled in seven Vaccine Safety Datalink (VSD) sites. § After standardizing mortality rates by age and sex, this study found that COVID-19 vaccine recipients had lower non-COVID-19 mortality than did unvaccinated persons. After adjusting for demographic characteristics and VSD site, this study found that adjusted relative risk (aRR) of non-COVID-19 mortality for the Pfizer-BioNTech vaccine was 0.41 (95% confidence interval [CI] = 0.38-0.44) after dose 1 and 0.34 (95% CI = 0.33-0.36) after dose 2. The aRRs of non-COVID-19 mortality for the Moderna vaccine were 0.34 (95% CI = 0.32-0.37) after dose 1 and 0.31 (95% CI = 0.30-0.33) after dose 2. The aRR after receipt of the Janssen vaccine was 0.54 (95% CI = 0.49-0.59). There is no increased risk for mortality among COVID-19 vaccine recipients. This finding reinforces the safety profile of currently approved COVID-19 vaccines in the United States., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Runxin Huang reports support for attending meetings or travel from Dynavax Technologies. Nicola P. Klein reports institutional support from Pfizer, Sanofi Pasteur, Merck, GlaxoSmithKline, and Protein Science (now Sanofi Pasteur to support vaccine studies). Elizabeth G. Liles reports research contracts from the National Human Genome Research Institute and Pfizer. Kerresa Morrissette reports research contracts from the National Institutes of Health, GlaxoSmithKline, and Merck Sharp & Dohme Corporation, outside the submitted work. No other potential conflicts of interest were disclosed.

Background: Dramatic decreases in outpatient visits and sudden increases in telehealth visits were observed during the COVID-19 pandemic, but it was unclear whether these changes differed by patient demographics and socioeconomic status., Objective: This study aimed to assess the impact of the pandemic on in-person outpatient and telehealth visits (telephone and video) by demographic characteristics and household income in a diverse population., Methods: We calculated weekly rates of outpatient and telehealth visits by age, sex, race/ethnicity, and neighborhood-level median household income among members of Kaiser Permanente Southern California (KPSC) from January 5, 2020, to October 31, 2020, and the corresponding period in 2019. We estimated the percentage change in visit rates during the early pandemic period (March 22 to April 25, 2020) and the late pandemic period (October 4 to October 31, 2020) from the prepandemic period (January 5 to March 7, 2020) in Poisson regression models for each subgroup while adjusting for seasonality using 2019 data. We examined if the changes in visit rates differed by subgroups statistically by comparing their 95% CIs., Results: Among 4.56 million KPSC members enrolled in January 2020, 15.0% (n=682,947) were ≥65 years old, 51.5% (n=2,345,020) were female, 39.4% (n=1,795,994) were Hispanic, and 7.7% (n=350,721) lived in an area of median household income

Background: The COVID-19 pandemic has caused an abrupt reduction in the use of in-person health care, accompanied by a corresponding surge in the use of telehealth services. However, the extent and nature of changes in health care utilization during the pandemic may differ by care setting. Knowledge of the impact of the pandemic on health care utilization is important to health care organizations and policy makers., Objective: The aims of this study are (1) to evaluate changes in in-person health care utilization and telehealth visits during the COVID-19 pandemic and (2) to assess the difference in changes in health care utilization between the pandemic year 2020 and the prepandemic year 2019., Methods: We retrospectively assembled a cohort consisting of members of a large integrated health care organization, who were enrolled between January 6 and November 2, 2019 (prepandemic year), and between January 5 and October 31, 2020 (pandemic year). The rates of visits were calculated weekly for four settings: inpatient, emergency department (ED), outpatient, and telehealth. Using Poisson models, we assessed the impact of the pandemic on health care utilization during the early days of the pandemic and conducted difference-in-deference (DID) analyses to measure the changes in health care utilization, adjusting for the trend of health care utilization in the prepandemic year., Results: In the early days of the pandemic, we observed significant reductions in inpatient, ED, and outpatient utilization (by 30.2%, 37.0%, and 80.9%, respectively). By contrast, there was a 4-fold increase in telehealth visits between weeks 8 (February 23) and 12 (March 22) in 2020. DID analyses revealed that after adjusting for prepandemic secular trends, the reductions in inpatient, ED, and outpatient visit rates in the early days of the pandemic were 1.6, 8.9, and 367.2 visits per 100 person-years (P<.001), respectively, while the increase in telehealth visits was 272.9 visits per 100 person-years (P<.001). Further analyses suggested that the increase in telehealth visits offset the reduction in outpatient visits by week 26 (June 28, 2020)., Conclusions: In-person health care utilization decreased drastically during the early period of the pandemic, but there was a corresponding increase in telehealth visits during the same period. By end-June 2020, the combined outpatient and telehealth visits had recovered to prepandemic levels., (©Stanley Xu, Sungching Glenn, Lina Sy, Lei Qian, Vennis Hong, Denison S Ryan, Steven Jacobsen. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 29.04.2021.)

Purpose  The aim of this study was to evaluate whether the simulated tissue models may be used in place of animal-based model for corneal laceration repair for surgical skills acquisition. Design  Prospective randomized controlled trial. Participants  Seventy-nine military and civilian 2nd- and 3rd-year ophthalmology residents and 16 staff ophthalmologists participating in the Tri-Service Ocular Trauma Skills Laboratory at the Uniformed Services University (Bethesda, MD). Methods  Resident ophthalmologists underwent preliminary evaluation of their ability to close a 5-mm linear, full-thickness corneal laceration involving the visual axis. They then were randomized to undergo 90 to 120 minutes of either simulator-based (SIM) or swine cadaveric-tissue-based (CADAVER) corneal laceration repair. The same evaluation was performed post training. On a more limited basis, the study was repeated for attending ophthalmologists to act as a pilot for future analysis and test efficacy for "refresher" training. Main Outcome Measures  Successful wound closure with secondary outcomes of suture length, tension, depth, and orientation, as graded by attending ophthalmologists. Results  No significant difference in CADAVER versus SIM groups in the primary outcome of watertight wound closure of the corneal laceration. CADAVER group performed better than SIM group for certain metrics (suture depth, p  = 0.009; length, p  = 0.003; and tension, p  = 0.043) that are associated with poor wound closure and increased amount of induced corneal astigmatism. For attending ophthalmologists, six of the eight in each group (SIM and CADAVER) retained or improved their skills. Conclusions  For resident ophthalmologists, SIM training is sufficient for achieving the primary outcome of watertight wound closure. However, CADAVER training is superior for wound metrics for the ideal closure. For attending ophthalmologists, SIM training may be useful for retention of skills., Competing Interests: Conflict of Interest No conflicting relationship exists for any author on this article., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Research has shown that compression of muscle can lead to a change in muscle force. Most studies show compression to lead to a reduction in muscle force, although recent research has shown that increases are also possible. Based on methodological differences in the loading design between studies, it seems that muscle length and the direction of transverse loading influence the effect of muscle compression on force production. Thus, in our current study we implement these two factors to influence the effects of muscle loading. In contrast to long resting length of the medial gastrocnemius (MG) in most studies, we use a shorter MG resting length by having participant seated with their knees at a 90° angle. Where previous studies have used unidirectional loads to compress the MG, in this study we applied a multidirectional load using a sling setup. Multidirectional loading using a sling setup has been shown to cause muscle force reductions in previous research. As a result of our choices in experimental design we observed changes in the effects of muscle loading compared to previous research. In the present study we observed no changes in muscle force due to muscle loading. Muscle thickness and pennation angle showed minor but significant increases during contraction. However, no significant changes occurred between unloaded and loaded trials. Fascicle thickness and length showed different patterns of change compared to previous research. We show that muscle loading does not result in force reduction in all situations and is possibly linked to differences in muscle architecture and muscle length., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ryan, Stutzig, Helmer, Siebert and Wakeling.)

Lipids in complex, protein-enriched films at air/liquid interfaces reduce surface tension. In the absence of this benefit, the light refracting and immunoprotective tear film on eyes would collapse. Premature collapse, coupled with chronic inflammation compromising visual acuity, is a hallmark of dry eye disease affecting 7 to 10% of individuals worldwide. Although collapse seems independent of mutation (unlike newborn lung alveoli), selective proteome and possible lipidome changes have been noted. These include elevated tissue transglutaminase and consequent inactivation through C-terminal cross-linking of the tear mitogen lacritin, leading to significant loss of lacritin monomer. Lacritin monomer restores homeostasis via autophagy and mitochondrial fusion and promotes basal tearing. Here, we discover that lacritin monomer C-terminal processing, inclusive of cysteine, serine, and metalloproteinase activity, generates cationic amphipathic α-helical proteoforms. Such proteoforms (using synthetic peptide surrogates) act like alveolar surfactant proteins to rapidly bind and stabilize the tear lipid layer. Immunodepletion of C- but not N-terminal proteoforms nor intact lacritin, from normal human tears promotes loss of stability akin to human dry eye tears. Stability of these and dry eye tears is rescuable with C- but not N-terminal proteoforms. Repeated topical application in rabbits reveals a proteoform turnover time of 7 to 33 h with gradual loss from human tear lipid that retains bioactivity without further processing. Thus, the processed C-terminus of lacritin that is deficient or absent in dry eye tears appears to play a key role in preventing tear film collapse and as a natural slow release mechanism that restores epithelial homeostasis., Competing Interests: Conflict of interest G. W. L. is cofounder and CSO, and MGO is CMO of TearSolutions, Inc. G. A. G., M. S., J. R., K. D. T., C. S., D. S. R., R. K. S., J. P. K., J. M. H., K. L. H., A. L., T. S., R. L. M. declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study we examined how the strain energies within a muscle are related to changes in longitudinal force when the muscle is exposed to an external transverse load. We implemented a three-dimensional (3D) finite element model of contracting muscle using the principle of minimum total energy and allowing the redistribution of energy through different strain energy-densities. This allowed us to determine the importance of the strain energy-densities to the transverse forces developed by the muscle. We ran a series of in silica experiments on muscle blocks varying in initial pennation angle, muscle length, and external transverse load. As muscle contracts it maintains a near constant volume. As such, any changes in muscle length are balanced by deformations in the transverse directions such as muscle thickness or muscle width. Muscle develops transverse forces as it expands. In many situations external forces act to counteract these transverse forces and the muscle responds to external transverse loads while both passive and active. The muscle blocks used in our simulations decreased in thickness and pennation angle when passively compressed and pushed back on the load when they were activated. Activation of the compressed muscle blocks led either to an increase or decrease in muscle thickness depending on whether the initial pennation angle was less than or greater than 15°, respectively. Furthermore, the strain energy increased and redistributed across the different strain-energy potentials during contraction. The volumetric strain energy-density varied with muscle length and pennation angle and was reduced with greater transverse load for most initial muscle lengths and pennation angles. External transverse load reduced the longitudinal muscle force for initial pennation angles of β 0 = 0°. Whereas for pennate muscle (β 0 > 0°) longitudinal force changed (increase or decrease) depending on the muscle length, pennation angle and the direction of the external load relative to the muscle fibres. For muscle blocks with initial pennation angles β 0 ≤ 20° the reduction in longitudinal muscle force coincided with a reduction in volumetric strain energy-density., (Copyright © 2020 Ryan, Domínguez, Ross, Nigam and Wakeling.)

Pregnant women might be at increased risk for severe coronavirus disease 2019 (COVID-19), possibly related to changes in their immune system and respiratory physiology* (1). Further, adverse birth outcomes, such as preterm delivery and stillbirth, might be more common among pregnant women infected with SARS-CoV-2, the virus that causes COVID-19 (2,3). Information about SARS-CoV-2 infection during pregnancy is rapidly growing; however, data on reasons for hospital admission, pregnancy-specific characteristics, and birth outcomes among pregnant women hospitalized with SARS-CoV-2 infections are limited. During March 1-May 30, 2020, as part of Vaccine Safety Datalink (VSD) † surveillance of COVID-19 hospitalizations, 105 hospitalized pregnant women with SARS-CoV-2 infection were identified, including 62 (59%) hospitalized for obstetric reasons (i.e., labor and delivery or another pregnancy-related indication) and 43 (41%) hospitalized for COVID-19 illness without an obstetric reason. Overall, 50 (81%) of 62 pregnant women with SARS-CoV-2 infection who were admitted for obstetric reasons were asymptomatic. Among 43 pregnant women hospitalized for COVID-19, 13 (30%) required intensive care unit (ICU) admission, six (14%) required mechanical ventilation, and one died from COVID-19. Prepregnancy obesity was more common (44%) among pregnant women hospitalized for COVID-19 than that among asymptomatic pregnant women hospitalized for obstetric reasons (31%). Likewise, the rate of gestational diabetes (26%) among pregnant women hospitalized for COVID-19 was higher than it was among women hospitalized for obstetric reasons (8%). Preterm delivery occurred in 15% of pregnancies among 93 women who delivered, and stillbirths (fetal death at ≥20 weeks' gestation) occurred in 3%. Antenatal counseling emphasizing preventive measures (e.g., use of masks, frequent hand washing, and social distancing) might help prevent COVID-19 among pregnant women, § especially those with prepregnancy obesity and gestational diabetes, which might reduce adverse pregnancy outcomes., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Denison S. Ryan reports grants from Amgen, Merck & Co., and Radius Health and other support from O.N. Diagnostics outside the submitted work. Allison L. Naleway reports grants from Pfizer outside the submitted work. Nicola P. Klein reports grants from Sanofi Pasteur, GlaxoSmithKline, Pfizer, Merck & Co., and Protein Science outside the submitted work. No other potential conflicts of interest were disclosed.

Background: To analyze the final visual acuity (VA) of neuro-ophthalmologic injuries (NOI) in combat ocular trauma and to study the association of NOI with systemic neurologic injury (SNI) and traumatic brain injury (TBI)., Methods: The Walter Reed Ocular Trauma Database was reviewed. Inclusion criteria were any US service member and Department of Defense civilians who suffered NOI, SNI, or TBI in Operation Iraqi Freedom or Operation Enduring Freedom. The primary outcome measure was the rate of poor final VA in patients with an NOI with secondary outcome measures the rate of SNI and TBI. in patients with NOI., Results: One hundred seventy-eight (20.00%) of 890 eyes had an NOI. Optic nerve injury was observed in 79 (44.38%) eyes, other cranial nerve injury in 68 (38.20%), Horner syndrome in 4 (2.25%), diplopia in 45 (25.28%), and ptosis in 13 (7.30%). In patients with NOI, 76 (42.69%) eyes had a final VA less than 20/200. In injured eyes (n = 359) of patients (n = 251) with TBI, 154 eyes (34.26%) had a final VA less than 20/200. In multivariate analysis, optic nerve injury (P < 0.001), unlike TBI (P = 0.47), was associated with final VA less than 20/200. SNI (n = 229) had a statistically significant association (odds ratio 29.8, 95% confidence interval 19.2-47.8, P < 0.001) with NOI. Optic nerve injury and cranial nerve injury were associated with TBI and SNI (all, P < 0.001)., Conclusion: Optic nerve injury and cranial nerve injury are associated with TBI and SNI. Optic nerve injury, but not TBI or cranial nerve injury, is associated with a poor final VA.

During contraction the energy of muscle tissue increases due to energy from the hydrolysis of ATP. This energy is distributed across the tissue as strain-energy potentials in the contractile elements, strain-energy potential from the 3D deformation of the base-material tissue (containing cellular and extracellular matrix effects), energy related to changes in the muscle's nearly incompressible volume and external work done at the muscle surface. Thus, energy is redistributed through the muscle's tissue as it contracts, with only a component of this energy being used to do mechanical work and develop forces in the muscle's longitudinal direction. Understanding how the strain-energy potentials are redistributed through the muscle tissue will help enlighten why the mechanical performance of whole muscle in its longitudinal direction does not match the performance that would be expected from the contractile elements alone. Here we demonstrate these physical effects using a 3D muscle model based on the finite element method. The tissue deformations within contracting muscle are large, and so the mechanics of contraction were explained using the principles of continuum mechanics for large deformations. We present simulations of a contracting medial gastrocnemius muscle, showing tissue deformations that mirror observations from magnetic resonance imaging. This paper tracks the redistribution of strain-energy potentials through the muscle tissue during fixed-end contractions, and shows how fibre shortening, pennation angle, transverse bulging and anisotropy in the stress and strain of the muscle tissue are all related to the interaction between the material properties of the muscle and the action of the contractile elements., (Copyright © 2020 Wakeling, Ross, Ryan, Bolsterlee, Konno, Domínguez and Nigam.)

Background: This study evaluated the VIsion PERformance (VIPER) simulator's ability to assess the functional visual performance in warfighters conducting civilian and military tasks., Methods: Thirty service members, aged 25-35 years old with a best corrected distance visual acuity (VA) better than or equal to 20/20 or logarithm of the minimum angle of resolution (logMAR) 0.00, were randomized to locate and identify road signs and mock improvised explosive devices (IEDs) under either daytime conditions or with infrared imagery, with (cc) and without (sc) wearing their habitual correction. Participants also underwent binocular uncorrected (UDVA) and corrected (CDVA) visual assessment, refraction, contrast sensitivity testing and wavefront aberrometry., Results: The mean age was 28.47 years. The manifest spherical equivalent was - 3.16 ± 1.75 diopters (D), the UDVA in both eyes (OU) was logMAR 0.83 ± 0.47, and the CDVA OU was - 0.11 ± 0.06. For VIPER, the mean difference in the detection distance (DD) for road signs ccDD vs. scDD was 76.7 ± 52.8 m (P < 0.001). The average difference in identification distance (ID) ccID vs. scID was 13.9 ± 6.3 m (P < 0.001). The mean accuracies were 83.5 and 27.9% for cc and sc, respectively (P < 0.001). The regression analysis indicated that a 1.6 m change in the distance accounts for a 1% change in the accuracy (P = 0.002). Without correction, a 4.1 m change accounts for a 1% change in the accuracy (P < 0.001). The average IED ccDD was 29.9 ± 8.2 m, and that for scDD was 13.2 ± 13.6 m (P < 0.001). The average IED ccID was 32.2 ± 6.2 m and that for the scID was 7.4 ± 10.3 m (P < 0.001). The mean IED identification accuracy was 46.7 and 11.4% for cc and sc, respectively (P < 0.001)., Conclusions: The preliminary results reflect VIPER's ability to assess functional visual performance when detecting and identifying signs and IEDs. Furthermore, VIPER is able to detect performance changes with and without correction.

It has been demonstrated that unidirectional transversal muscle loading induced by a plunger influences muscle shape and reduces muscle force. The interaction between muscle and transversal forces may depend on specific neuromuscular properties that change during a lifetime. Compression garments, applying forces from all directions in the transverse plane, are widely used in sports for example to improve performance. Differences in the loading direction (unidirectional vs. multidirectional) may have an impact on force generating capacity of muscle and, thus, on muscle performance. The aim of this study was to examine the effect of multidirectional transversal loads, using a sling looped around the calf, on the isometric force during plantarflexions. Young male adults (25.7 ± 1.5 years, n = 15) were placed in a prone position in a calf press apparatus. The posterior tibial nerve was stimulated to obtain the maximal double-twitch force of the calf muscles with (59.4 and 108.4 N) and without multidirectional transverse load. Compared to the unloaded condition, the rate of force development ( RFD ) was reduced by 5.0 ± 8.1% ( p = 0.048) and 6.9 ± 10.7% ( p = 0.008) for the 59.4 and 108.4 N load, respectively. No significant reduction (3.2 ± 4.8%, p = 0.141) in maximum muscle force ( F m ) was found for the lower load (59.4 N), but application of the higher load (108.4 N) resulted in a significant reduction of F m by 4.8 ± 7.0% ( p = 0.008). Mean pressures induced in this study (14.3 and 26.3 mm Hg corresponding to the 59.4 and 108.4 N loads, respectively) are within the pressure range reported for compression garments. Taking the results of the present study into account, a reduction in maximum muscle force would be expected for compression garments with pressures ≥26.3 mm Hg. However, it should be noted that the loading condition (sling vs. compression garment) differs and that compression garments may influence other mechanisms contributing to force generation. For example, wearing compression garments may enhance sport performance by enhanced proprioception and reduced muscle oscillation. Thus, superposition of several effects should be considered when analyzing the impact of compression garments on more complex sport performance.

Muscles undergo cycles of length change and force development during locomotion, and these contribute to their work and power production to drive body motion. Muscle fibers are typically considered to be linear actuators whose stress depends on their length, velocity, and activation state, and whose properties can be scaled up to explain the function of whole muscles. However, experimental and modeling studies have shown that a muscle's stress additionally depends on inactive and passive tissues within the muscle, the muscle's size, and its previous contraction history. These effects have not been tested under common sets of contraction conditions, especially the cyclic contractions that are typical of locomotion. Here we evaluate the relative effects of size, history-dependent, activation and three-dimensional effects on the work and power produced during cyclic contractions of muscle models. Simulations of muscle contraction were optimized to generate high power outputs: this resulted in the muscle models being largely active during shortening, and inactive during lengthening. As such, the history-dependent effects were dominated by force depression during simulated active shortening rather than force enhancement during active stretch. Internal work must be done to deform the muscle tissue, and to accelerate the internal muscle mass, resulting in reduced power and work that can be done on an external load. The effect of the muscle mass affects the scaling of muscle properties, with the inertial costs of contraction being relatively greater at larger sizes and lower activation levels.

Background: Retreatments are sometimes necessary to correct residual or induced refractive errors following refractive surgery. Many different combinations of primary treatment methods and retreatment techniques have been studied, however, few studies have investigated wavefront-optimized (WFO) technology for retreatment following primary refractive surgery. This study aimed to report the outcomes of WFO photorefractive keratectomy (PRK) retreatments of refractive error following previous laser refractive surgery with PRK, laser in situ keratomileusis (LASIK), or laser-assisted subepithelial keratectomy (LASEK)., Methods: We reviewed records of patients who underwent WFO PRK retreatments using the Allegretto Wave Eye-Q 400 Hz Excimer Laser System (Alcon Surgical) between January 2008 and April 2011 at Walter Reed Army Medical Center and Madigan Army Medical Center. Outcomes were recorded in terms of uncorrected distance visual acuity (UDVA), manifest refraction spherical equivalent (MRSE), corrected distance visual acuity (CDVA), and complications at 1 month (M), 3 M, and 6 M post-op., Results: Seventy-eight patients (120 eyes) underwent WFO PRK retreatment during the study period. Primary surgery was surface ablation in 87 eyes (78 PRK, 9 LASEK) and LASIK in 33 eyes. The mean spherical equivalent before retreatment was -0.79 ± 0.94 D (-3.00 to 1.88 D). UDVA was ≥ 20/20 in 69 eyes (60.0 %) at 1 M, 54 eyes (71.1 %) at 3 M, and 27 eyes (73.0 %) at 6 M follow-up. MRSE was within ±0.50 D of emmetropia in 78 eyes (67.8 %) at 1 M, 59 eyes (77.6 %) at 3 M, and 25 eyes (67.6 %) at 6 M follow-up. CDVA was maintained within ±1 line of pre-op in 113 of 115 eyes (98.3 %) at 1 M, 74 of 76 eyes (97.4 %) at 3 M, and 37 eyes (100 %) at 6 M follow-up., Conclusion: Although follow-up was limited beyond 3 M, WFO PRK retreatments in patients with residual refractive error may be a safe and effective procedure. Further studies are necessary to determine the long-term safety and stability of outcomes.

Antimicrobial peptides are important as the first line of innate defense, through their tendency to disrupt bacterial membranes or intracellular pathways and potentially as the next generation of antibiotics. How they protect wet epithelia is not entirely clear, with most individually inactive under physiological conditions and many preferentially targeting Gram-positive bacteria. Tears covering the surface of the eye are bactericidal for Gram-positive and -negative bacteria. Here we narrow much of the bactericidal activity to a latent C-terminal fragment in the prosecretory mitogen lacritin and report that the mechanism combines membrane permeabilization with rapid metabolic changes, including reduced levels of dephosphocoenzyme A, spermidine, putrescine, and phosphatidylethanolamines and elevated alanine, leucine, phenylalanine, tryptophan, proline, glycine, lysine, serine, glutamate, cadaverine, and pyrophosphate. Thus, death by metabolic stress parallels cellular attempts to survive. Cleavage-dependent appearance of the C-terminal cationic amphipathic α-helix is inducible within hours by Staphylococcus epidermidis and slowly by another mechanism, in a chymotrypsin- or leupeptin protease-inhibitable manner. Although bactericidal at low micromolar levels, within a biphasic 1-10 nM dose optimum, the same domain is mitogenic and cytoprotective for epithelia via a syndecan-1 targeting mechanism dependent on heparanase. Thus, the C terminus of lacritin is multifunctional by dose and proteolytic processing and appears to play a key role in the innate protection of the eye, with wider potential benefit elsewhere as lacritin flows from exocrine secretory cells., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Objective: To explore potential weight-related disparities in the quality of care for adults with diabetes in a large managed care health plan according to recommended quality indicators., Design: Cross-sectional analysis., Methods: A total of 164,721 Kaiser Permanente Southern California members aged 18 to 75 years with diabetes who had 1 or more health encounters with a weight and height measurement between July 1, 2007, and June 30, 2008, were identified. The 9 Healthcare Effectiveness Data and Information Set (HEDIS) quality-of-care measures were examined: 4 screening measures (glycated hemoglobin [A1C], retinal examination, lipids, and nephropathy) and 5 control measures (2 for A1C, 2 for blood pressure, and 1 for low-density lipoprotein cholesterol [LDLC]), using data extracted from electronic health records (EHRs). Weight and height from the EHR were used to calculate body mass index (BMI). Adjusted odds ratios and 95% confidence intervals were calculated to examine the association between BMI categories and HEDIS quality-of-care measures., Results: Among individuals with diabetes, 12% were in the healthy-weight category, 30% were overweight, and 28%, 17%, and 14% were in obese categories I, II, and III, respectively. Overweight and obese individuals were more likely than their healthy-weight counterparts to have screening measures performed. However, among those tested or screened, overweight and obese individuals were less likely to have their A1C and blood pressure controlled. LDL-C control increased as BMI increased., Conclusions: These findings highlight the need for interventions to improve glycemic and blood pressure control among overweight and obese patients with diabetes.

Purpose: Molar accounting of bioactive fluids can expose new regulatory mechanisms in the growing proteomic focus on epithelial biology. Essential for the viability of the surface epithelium of the eye and for normal vision is the thin, but protein-rich, tear film in which the small tear glycoprotein lacritin appears to play a prominent prosecretory, cytoprotective, and mitogenic role. Although optimal bioactive levels in cell culture are 1 to 10 nM over a biphasic dose optimum, ELISA suggests a sustained tear lacritin concentration in the midmicromolar range in healthy adults. Here we identify a reconciling mechanism., Methods: Monoclonal anti-lacritin 1F5 antibody was generated, and applied together with a new anti-C-terminal polyclonal antibody to tear and tissue Western blotting. In vitro tissue transglutaminase (Tgm2) cross-linking was monitored and characterized by mass spectrometry., Results: Blotting for lacritin in human tears or saliva surprisingly detected immunoreactive material with a higher molecular weight and prominence equal or exceeding the ∼23 to 25 kDa band of monomeric glycosylated lacritin. Exogenous Tgm2 initiated lacritin cross-linking within 1 minute and was complete by 90 minutes-even with as little as 0.1 nM lacritin, and involved the donors lysine 82 and 85 and the acceptor glutamine 106 in the syndecan-1 binding domain. Lacritin spiked into lacritin-depleted tears formed multimers, in keeping with ∼0.6 μM TGM2 in tears. Cross-linking was absent when Tgm2 was inactive, and cross-linked lacritin, unlike recombinant monomer, bound syndecan-1 poorly., Conclusions: Since syndecan-1 binding is necessary for lacritin mitogenic and cytoprotective activities, TGM2 cross-linking negatively regulates lacritin bioactivity.

Purpose. To evaluate the use of ocular imaging to enhance management and diagnosis of war-related anterior segment ocular injuries. Methods. This study was a prospective observational case series from an ongoing IRB-approved combat ocular trauma tracking study. Subjects with anterior segment ocular injury were imaged, when possible, using anterior segment optical coherence tomography (AS-OCT), confocal microscopy (CM), and slit lamp biomicroscopy. Results. Images captured from participants with combat ocular trauma on different systems provided comprehensive and alternate views of anterior segment injury to investigators. Conclusion. In combat-related trauma of the anterior segment, adjunct image acquisition enhances slit lamp examination and enables real time In vivo observation of the cornea facilitating injury characterization, progression, and management.

Purpose: Several small proteomic studies suggest that the prosecretory tear protein lacritin may be selectively downregulated in dry eye syndrome and in blepharitis, yet little information is available about normal baseline levels. This study assessed lacritin levels in tears from healthy individuals and addressed whether they differ according to sex, age, or time of day., Methods: Rabbit antibodies against lacritin N-terminal peptide EDASSDSTGADPAQEAGTS (Pep Lac N-Term) were generated and characterized against human recombinant lacritin and N-65 truncation mutant. Basal tears were collected from 66 healthy individuals ranging in age from 18 to 52 years, and at four times during one 24-hour period from 34 other individuals. Lacritin levels were then analyzed by ELISA and Western blotting., Results: Anti-Pep Lac N-Term bound lacritin, but not truncation mutant N-65 that lacks the N-terminal antigenic site. Tear lacritin levels followed a normal distribution with a mean of 4.2 ± 1.17 ng/100 ng total tear protein. Levels differed little by age or sex, and decreased slightly between 4 and 8 hours in a 24-hour cycle. Tear-blocking effects were minimal, as suggested by spiking of tears with recombinant lacritin., Conclusions: Anti-Pep Lac N-Term-detectable lacritin comprises ~4.2 ng/100 ng total tear protein in healthy individuals, with no significant differences between males and females or among individuals between 18 and 52 years old. Levels decrease slightly in the late afternoon. These findings provide a baseline for future immunodiagnostic studies of lacritin in dry eye and other ocular diseases.

A number of non-steroidal estrogenic substances are common naturally-occurring constituents of human foods. Concern over dietary estrogens has focused largely on the consumption of trace amounts of diethylstilbestrol (DES) from tissues of cattle fed the compound as a growth stimulant. Human exposure to naturally-occurring fungal and phytoestrogens in foods is, however, substantially larger than exposure to DES in animal tissues. Occurrence, potency and toxicity of the estrogenic isoflavones, coumestans and resorcylic acid lactones are reviewed.

The inhibition of proteolytic enzymes by protein inhibitors is accompanied by the formation of unusually stable complexes. The recognition of a specific substrate-like amino acid on the inhibitor is believed to be the initial event of the inhibitory process. In addition to the interactions involved in the binding of a good substrate, a variety of other noncovalent interactions are known to stabilize the complex. The formation of stable complexes between several inactive derivatives of proteolytic enzymes and a variety of protein inhibitors suggests strongly that the formation of any species resembling catalytic intermediates is unnecessary for inhibition. We have examined the interaction between several avian ovomucoids and alpha-chymotrypsin in which histidine-57 has been converted to 3-methylhistidine-57. This derivative is easily prepared and can be isolated by affinity chromatography. Methylchymotrypsin retains unaltered its ability to bind specific substrates, but is essentially inactive. In spite of this loss of enzymatic activity, methylchymotrypsin forms strong complexes with several inhibitors. In addition, methylchymotrypsin which has been covalently linked to Sepharose is particularly useful for the isolation of protein inhibitors without the complications due to isolation of a mixture of partially cleaved forms of the inhibitor.

The major globulin of the French bean (Phaseolus vulgaris L.) undergoes a reversible pH-dependent polymerization. At pH values above 6.5, the monomeric form of the protein predominates; and at pH values below 6.5, the protein occurs as a polymer, probably a tetramer. At extremes of pH, the protein dissociates further into peptides. The reversible pH-dependent interaction between globulin subunits is used in this report as the basis for an affinity chromatography procedure for isolation of the globulin. The major globulin from several genetic variants can be obtained in gram quantities and does not indicate the presence of any impurities on discontinuous sodium dodecyl sulfate gel electrophoresis.