Distribution of COVID-19 mitigation measures by industry and work arrangement-US blood donors, May 2021-December 2021.

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) mitigation measures in workplaces of employed US blood donors by industry and work arrangement. METHODS: During May-December 2021, blood donors responded to a survey; we describe the distribution of reported workplace mitigation measures by industry and work arrangement, organized using the hierarchy of controls. RESULTS: Of 53,433 respondents representing 21 industries, ventilation upgrades were reported by 4%-38% of respondents (overall: 20%); telework access ranged from 14%-80% (53% overall). Requiring masks (overall: 84%; range: 40%-94%), physical distancing (77%; 51%-86%), paid leave for illness (70%; 38%-87%), and encouraging vaccination (61%; 33%-80%) were common. Independent workers reported fewer mitigation measures than those in traditional employment settings. CONCLUSIONS: Mitigation measures varied by industry and work arrangement. Some mitigation measures may be challenging to implement or irrelevant in certain industries, supporting the idea that mitigation is not a one-size-fits-all strategy. POLICY IMPLICATIONS: Tailored strategies to mitigate workplace risks of disease transmission are vital. Strategies should rely on effective methods for identifying workplace controls (e.g., through the hierarchy of controls) and account for industry-specific characteristics and workplace environments.

Prevalence of SARS-CoV-2 infection among US blood donors by industry, May-December 2021.

BACKGROUND: Work is a social determinant of health that is often overlooked. There are major work-related differences in the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and death, but there have been few analyses of infection rates across industry groups. To date, only one national assessment of SARS-CoV-2 infection prevalence by industry based on self-report has been completed. No study has looked at seroprevalence of COVID-19 by industry. METHODS: During May-December 2021, blood donors with SARS-CoV-2 antinucleocapsid testing were sent an electronic survey about their work. Free-text industry responses were classified using the North American Industry Classification System. We estimated seroprevalence and 95% confidence intervals (CIs) of SARS-CoV-2 infection by industry. RESULTS: Of 57,726 donors, 7040 (12%, 95% CI: 11.9%-12.5%) had prior SARS-CoV-2 infection. Seroprevalence was highest among Accommodation & Food Services (19.3%, 95% CI: 17.1%-21.6%), Mining, Quarrying, and Oil and Gas Extraction (19.2%, 95% CI: 12.8%-27.8%), Healthcare & Social Assistance (15.6%, 95% CI: 14.9%-16.4%), and Construction (14.7%, 95% CI: 13.1%-16.3%). Seroprevalence was lowest among Management of Companies & Enterprises (6.5%, 95% CI: 3.5%-11.5%), Professional Scientific & Technical Services (8.4%, 95% CI: 7.7%-9.0%), and Information (9.9%, 95% CI: 8.5%-11.5%). CONCLUSIONS: While workers in all industries had serologic evidence of SARS-CoV-2 infection, certain sectors were disproportionately impacted. Disease surveillance systems should routinely collect work characteristics so public health and industry leaders can address health disparities using sector-specific policies.

Health Hazard Evaluations of occupational cancer cluster concerns: the USA, January 2001-December 2020.

OBJECTIVES: To describe recent investigations of potential workplace cancer clusters. METHODS: We identified Health Hazard Evaluations (HHEs) of cancer concerns during 2001-2020. We described information about industry, requestors, cancer characteristics, investigative procedures, and determinations about the presence of a cluster (ie, presence of excess cases, unusual case distribution or exposure). RESULTS: Of 5754 HHEs, 174 included cancer concerns, comprising 1%-5% of HHEs per year. In 123 HHEs, the cancer cluster concerns involved different cancer primary sites. Investigation procedures varied but included record review (n=63, 36%) and site visits (n=22, 13%). Of 158 HHEs with a cluster determination by investigator(s), 151 (96%) were not considered cancer clusters. In seven HHEs, investigators found evidence of a cluster, but occupational exposure to a carcinogen was not identified. CONCLUSIONS: The proportion of HHEs on workplace cancer cluster concerns remained steady over time; most did not meet the definition of a cluster or uncover an occupational cause. Public health practitioners can use this information to provide updated context when addressing workplace cancer cluster concerns and as motivation to refine investigative approaches. More broadly, this review highlights an opportunity to identify best practices on how to apply community cluster investigation methods to the workplace.

Neuroinflammatory disease disrupts the blood-CNS barrier via crosstalk between proinflammatory and endothelial-to-mesenchymal-transition signaling.

Breakdown of the blood-central nervous system barrier (BCNSB) is a hallmark of many neuroinflammatory disorders, such as multiple sclerosis (MS). Using a mouse model of MS, experimental autoimmune encephalomyelitis (EAE), we show that endothelial-to-mesenchymal transition (EndoMT) occurs in the CNS before the onset of clinical symptoms and plays a major role in the breakdown of BCNSB function. EndoMT can be induced by an IL-1ß-stimulated signaling pathway in which activation of the small GTPase ADP ribosylation factor 6 (ARF6) leads to crosstalk with the activin receptor-like kinase (ALK)-SMAD1/5 pathway. Inhibiting the activation of ARF6 both prevents and reverses EndoMT, stabilizes BCNSB function, reduces demyelination, and attenuates symptoms even after the establishment of severe EAE, without immunocompromising the host. Pan-inhibition of ALKs also reduces disease severity in the EAE model. Therefore, multiple components of the IL-1ß-ARF6-ALK-SMAD1/5 pathway could be targeted for the treatment of a variety of neuroinflammatory disorders.

Factors Associated With Severe Illness in Patients Aged <21 Years Hospitalized for COVID-19.

OBJECTIVES: To describe coronavirus disease 2019 (COVID-19)-related pediatric hospitalizations during a period of B.1.617.2 (Δ) variant predominance and to determine age-specific factors associated with severe illness. METHODS: We abstracted data from medical charts to conduct a cross-sectional study of patients aged <21 years hospitalized at 6 United States children's hospitals from July to August 2021 for COVID-19 or with an incidental positive severe acute respiratory syndrome coronavirus 2 test. Among patients with COVID-19, we assessed factors associated with severe illness by calculating age-stratified prevalence ratios (PR). We defined severe illness as receiving high-flow nasal cannula, positive airway pressure, or invasive mechanical ventilation. RESULTS: Of 947 hospitalized patients, 759 (80.1%) had COVID-19, of whom 287 (37.8%) had severe illness. Factors associated with severe illness included coinfection with respiratory syncytial virus (RSV) (PR 3.64) and bacteria (PR 1.88) in infants; RSV coinfection in patients aged 1 to 4 years (PR 1.96); and obesity in patients aged 5 to 11 (PR 2.20) and 12 to 17 years (PR 2.48). Having ≥2 underlying medical conditions was associated with severe illness in patients aged <1 (PR 1.82), 5 to 11 (PR 3.72), and 12 to 17 years (PR 3.19). CONCLUSIONS: Among patients hospitalized for COVID-19, factors associated with severe illness included RSV coinfection in those aged <5 years, obesity in those aged 5 to 17 years, and other underlying conditions for all age groups <18 years. These findings can inform pediatric practice, risk communication, and prevention strategies, including vaccination against COVID-19.

Hospitalizations of Children Aged 5-11 Years with Laboratory-Confirmed COVID-19 - COVID-NET, 14 States, March 2020-February 2022.

On October 29, 2021, the Food and Drug Administration expanded the Emergency Use Authorization for Pfizer-BioNTech COVID-19 vaccine to children aged 5-11 years; CDC's Advisory Committee on Immunization Practices' recommendation followed on November 2, 2021.* In late December 2021, the B.1.1.529 (Omicron) variant of SARS-CoV-2 (the virus that causes COVID-19) became the predominant strain in the United States,† coinciding with a rapid increase in COVID-19-associated hospitalizations among all age groups, including children aged 5-11 years (1). COVID-19-Associated Hospitalization Surveillance Network (COVID-NET)§ data were analyzed to describe characteristics of COVID-19-associated hospitalizations among 1,475 U.S. children aged 5-11 years throughout the pandemic, focusing on the period of early Omicron predominance (December 19, 2021-February 28, 2022). Among 397 children hospitalized during the Omicron-predominant period, 87% were unvaccinated, 30% had no underlying medical conditions, and 19% were admitted to an intensive care unit (ICU). The cumulative hospitalization rate during the Omicron-predominant period was 2.1 times as high among unvaccinated children (19.1 per 100,000 population) as among vaccinated¶ children (9.2).** Non-Hispanic Black (Black) children accounted for the largest proportion of unvaccinated children (34%) and represented approximately one third of COVID-19-associated hospitalizations in this age group. Children with diabetes and obesity were more likely to experience severe COVID-19. The potential for serious illness among children aged 5-11 years, including those with no underlying health conditions, highlights the importance of vaccination among this age group. Increasing vaccination coverage among children, particularly among racial and ethnic minority groups disproportionately affected by COVID-19, is critical to preventing COVID-19-associated hospitalization and severe outcomes.

Primary THA Using Thin Polyethylene Liners and Large Femoral Heads: A Minimum 5-Year Follow-Up.

BACKGROUND: Large femoral head sizes are commonly used in total hip arthroplasty (THA) to minimize the risk of instability. With small acetabular cup-size, large femoral head diameter often results in the use of thin polyethylene liners. The purpose of this study was to evaluate clinical and radiographic results of large femoral heads against thin polyethylene liners with minimum 5-year follow-up. METHODS: This was a retrospective review identifying 58 primary THAs utilizing thin polyethylene inserts from one manufacturer (X3 polyethylene, Stryker, Mahwah, NJ) and large femoral heads (36 mm or greater) with minimum 5-year follow-up. A total of 3 patients were deceased and 11 lost to follow-up, leaving 44 patients for review. All patients were female with mean age 65.7 (range 26-85) and mean body mass index (BMI) 29.9 (range 19.6-45.4). Average length of follow-up was 8.5 years (range 5.1-11.3). Outcome measures included survivorship, complications, PROMs and radiographic analysis. RESULTS: There were four revisions: two aseptic loosening, one prosthetic joint infection, and one recurrent dislocation. Average HOOS-Jr, FJS-12, and patient satisfaction using Likert score was 94.3/100, 92.9/100, and 4.69/5.00, respectively, with 94% of patients reporting being satisfied or very satisfied. Radiographic analysis at average of 8.5 years demonstrated well-fixed implants without evidence of progressive radiolucent lines, osteolysis, or failure of the polyethylene liner. Survivorship using failure of the thin polyethylene liner as the endpoint was 100% at an average of 8.5 years. CONCLUSION: Thin polyethylene liners used with large femoral head sizes in small acetabular cups demonstrated excellent results at average 8.5-year follow-up with no cases of liner fracture or osteolysis.

Hospitalised heat-related acute kidney injury in indoor and outdoor workers in the USA.

OBJECTIVES: To characterise heat-related acute kidney injury (HR-AKI) among US workers in a range of industries. METHODS: Two data sources were analysed: archived case files of the Occupational Safety and Health Administration's (OSHA) Office of Occupational Medicine and Nursing from 2010 through 2020; and a Severe Injury Reports (SIR) database of work-related hospitalisations that employers reported to federal OSHA from 2015 to 2020. Confirmed, probable and possible cases of HR-AKI were ascertained by serum creatinine measurements and narrative incident descriptions. Industry-specific incidence rates of HR-AKI were computed. A capture-recapture analysis assessed under-reporting in SIR. RESULTS: There were 608 HR-AKI cases, including 22 confirmed cases and 586 probable or possible cases. HR-AKI occurred in indoor and outdoor industries including manufacturing, construction, mail and package delivery, and solid waste collection. Among confirmed cases, 95.2% were male, 50.0% had hypertension and 40.9% were newly hired workers. Incidence rates of AKI hospitalisations from 1.0 to 2.5 hours per 100 000 workers per year were observed in high-risk industries. Analysis of overlap between the data sources found that employers reported only 70.6% of eligible HR-AKI hospitalisations to OSHA, and only 41.2% of reports contained a consistent diagnosis. CONCLUSIONS: Workers were hospitalised with HR-AKI in diverse industries, including indoor facilities. Because of under-reporting and underascertainment, national surveillance databases underestimate the true burden of occupational HR-AKI. Clinicians should consider kidney risk from recurrent heat stress. Employers should provide interventions, such as comprehensive heat stress prevention programmes, that include acclimatisation protocols for new workers, to prevent HR-AKI.

Characteristics and Clinical Outcomes of Children and Adolescents Aged <18 Years Hospitalized with COVID-19 - Six Hospitals, United States, July-August 2021.

During June 2021, the highly transmissible† B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating strain in the United States. U.S. pediatric COVID-19-related hospitalizations increased during July-August 2021 following emergence of the Delta variant and peaked in September 2021.§ As of May 12, 2021, CDC recommended COVID-19 vaccinations for persons aged ≥12 years,¶ and on November 2, 2021, COVID-19 vaccinations were recommended for persons aged 5-11 years.** To date, clinical signs and symptoms, illness course, and factors contributing to hospitalizations during the period of Delta predominance have not been well described in pediatric patients. CDC partnered with six children's hospitals to review medical record data for patients aged <18 years with COVID-19-related hospitalizations during July-August 2021.†† Among 915 patients identified, 713 (77.9%) were hospitalized for COVID-19 (acute COVID-19 as the primary or contributing reason for hospitalization), 177 (19.3%) had incidental positive SARS-CoV-2 test results (asymptomatic or mild infection unrelated to the reason for hospitalization), and 25 (2.7%) had multisystem inflammatory syndrome in children (MIS-C), a rare but serious inflammatory condition associated with COVID-19.§§ Among the 713 patients hospitalized for COVID-19, 24.7% were aged <1 year, 17.1% were aged 1-4 years, 20.1% were aged 5-11 years, and 38.1% were aged 12-17 years. Approximately two thirds of patients (67.5%) had one or more underlying medical conditions, with obesity being the most common (32.4%); among patients aged 12-17 years, 61.4% had obesity. Among patients hospitalized for COVID-19, 15.8% had a viral coinfection¶¶ (66.4% of whom had respiratory syncytial virus [RSV] infection). Approximately one third (33.9%) of patients aged <5 years hospitalized for COVID-19 had a viral coinfection. Among 272 vaccine-eligible (aged 12-17 years) patients hospitalized for COVID-19, one (0.4%) was fully vaccinated.*** Approximately one half (54.0%) of patients hospitalized for COVID-19 received oxygen support, 29.5% were admitted to the intensive care unit (ICU), and 1.5% died; of those requiring respiratory support, 14.5% required invasive mechanical ventilation (IMV). Among pediatric patients with COVID-19-related hospitalizations, many had severe illness and viral coinfections, and few vaccine-eligible patients hospitalized for COVID-19 were vaccinated, highlighting the importance of vaccination for those aged ≥5 years and other prevention strategies to protect children and adolescents from COVID-19, particularly those with underlying medical conditions.

Molecular Characterization of Mycoplasma pneumoniae Isolates in the United States from 2012 to 2018.

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. There are limited data in the United States on the molecular epidemiological characteristics of M. pneumoniae We collected 446 M. pneumoniae-positive specimens from 9 states between August 2012 and October 2018. Culture, antimicrobial susceptibility testing, P1 subtyping, and multilocus VNTR (variable-number tandem repeats) analysis (MLVA) were performed to characterize the isolates. Macrolide-resistant M. pneumoniae (MRMp) was detected in 37 (8.3%) specimens. P1 subtype 2 (P1-2) was the predominant P1 subtype (59.8%). P1 subtype distribution did not change significantly chronologically or geographically. The macrolide resistance rate in P1 subtype 1 (P1-1) samples was significantly higher than that in P1-2 (12.9% versus 5.5%). Six P1-2 variants were identified, including two novel types, and variant 2c was predominant (64.6%). P1-2 variants were distributed significantly differently among geographic regions. Classical P1-2 was more frequent in lower respiratory tract specimens and had longer p1 trinucleotide repeats. Classical P1-2 was most common in MRMp (35.7%), while variant 2c was most common in macrolide-susceptible M. pneumoniae (67.5%). Fifteen MLVA types were identified; 3-5-6-2 (41.7%), 4-5-7-2 (35.3%), and 3-6-6-2 (16.6%) were the major types, and four MLVA clusters were delineated. The distribution of MLVA types varied significantly over time and geographic location. The predominant MLVA type switched from 4-5-7-2 to 3-5-6-2 in 2015. MLVA type was associated with P1 subtypes and P1-2 variant types but not with macrolide resistance. To investigate the M. pneumoniae genotype shift and its impact on clinical presentations, additional surveillance programs targeting more diverse populations and prolonged sampling times are required.

Results of Cemented Posterior-Stabilized Total Knee Arthroplasty in Obese Patients With an Average 10-Year Follow-Up.

BACKGROUND: Obese and morbidly obese patients undergoing primary total knee arthroplasty (TKA) place significant stress at the bone-cement-implant interface over the life of the patient. The purpose of this study is to evaluate results of cemented, posterior-stabilized TKA in obese and morbidly obese patients at an average follow-up of 10 years. METHODS: Retrospective study of 181 patients who had a cemented, posterior-stabilized TKA between 2000 and 2013 with body mass index >35 at the time of surgery was conducted. Clinical data and radiographs were evaluated along with survivorship, complications, and revisions. Minimum follow-up was 5 years with an average follow-up of 10 years. RESULTS: There were 135 women and 46 men in the study, with mean age of 60.2 years (range 43-80), mean body mass index of 42.0 (range 35.1-66.1), and an average follow-up of 10 years (range 5-18). There were a total of 39 failures (22%) that underwent revision TKA surgery with mean time to revision of 8 years. Failures included 25 (14%) cases of aseptic loosening; 9 (5%) polyethylene wear; 2 (1%) prosthetic joint infection; and 3 additional revisions for instability, pain, and stiffness. There were a total of 11 cases of isolated tibial component loosening and 13 for both tibial and femoral loosening. Survivorship at 15 years with aseptic loosening as the endpoint was 86.7%, and for all causes 79.6% at 15 years. CONCLUSION: Aseptic loosening is the leading cause of failure following TKA in obese and morbidly obese patients with decreasing survivorship from 96.1% to 91.2% and 86.7% at 5, 10, and 15 years, respectively.

Macrolide-Resistant Mycoplasma pneumoniae in the United States as Determined from a National Surveillance Program.

There are sparse data to indicate the extent that macrolide-resistant Mycoplasma pneumoniae (MRMp) occurs in the United States or its clinical significance. Between 2015 and 2018, hospitals in 8 states collected and stored respiratory specimens that tested positive for M. pneumoniae and sent them to the University of Alabama at Birmingham, where real-time PCR was performed for detection of 23S rRNA mutations known to confer macrolide resistance. MRMp was detected in 27 of 360 specimens (7.5%). MRMp prevalence was significantly higher in the South and East (18.3%) than in the West (2.1%). A2063G was the predominant 23S rRNA mutation detected. MICs for macrolide-susceptible M. pneumoniae (MSMp) were ≤0.008 µg/ml, whereas MICs for MRMp were 16 to 32 µg/ml. Patients with MRMp infection were more likely to have a history of immunodeficiency or malignancy. Otherwise, there were no other significant differences in the clinical features between patients infected with MRMp and those infected with MSMp, nor were there any differences in radiographic findings, hospitalization rates, viral coinfections, the mean duration of antimicrobial treatment, or clinical outcomes. There was no significant change in MRMp incidence over time or according to age, sex, race/ethnicity, or status as an inpatient or an outpatient. Patients with MRMp were more likely to have received a macrolide prior to presentation, and their treatment was more likely to have been changed to a fluoroquinolone after presentation. This is the first national surveillance program for M. pneumoniae in the United States. Additional surveillance is needed to assess the clinical significance of MRMp and to monitor changes in MRMp prevalence.

Subepidermal Calcinosis in the Ocular Adnexa: A Systematic Review.

PURPOSE: To review the clinical and histopathologic findings associated with subepidermal calcinosis of the eyelids. METHODS: A systematic review of the literature on subepidermal calcinosis of the eyelids was performed. Cases included were idiopathic in nature and met the histologic criteria for subepidermal calcinosis with calcium deposits in the dermis of the skin. RESULTS: Twenty-one publications presenting 53 cases of subepidermal calcinosis involving the eyelids were published between 1970 and 2016. Males were affected more than females (67% vs. 33%), and 89% of patients were 21 years of age or younger. A total of 63% were non-Caucasian. Most cases involved a single lesion (82%), and lesions were most frequently located on the upper eyelid (63%). In 81% of cases, the lesion was less than 5 mm in diameter. When reported, the treatment of choice was complete surgical excision. CONCLUSIONS: Subepidermal calcinosis should be considered in the differential diagnosis of idiopathic lesions on the eyelid, particularly in young males with no history of systemic disease or laboratory abnormalities. These nodules usually present as painless, small, firm, mobile solitary cutaneous lesions with a predilection for the upper eyelid. Diagnosis is confirmed by histopathology, and treatment is with surgical excision.

Small GTPase ARF6 controls VEGFR2 trafficking and signaling in diabetic retinopathy.

The devastating sequelae of diabetes mellitus include microvascular permeability, which results in retinopathy. Despite clinical and scientific advances, there remains a need for new approaches to treat retinopathy. Here, we have presented a possible treatment strategy, whereby targeting the small GTPase ARF6 alters VEGFR2 trafficking and reverses signs of pathology in 4 animal models that represent features of diabetic retinopathy and in a fifth model of ocular pathological angiogenesis. Specifically, we determined that the same signaling pathway utilizes distinct GEFs to sequentially activate ARF6, and these GEFs exert distinct but complementary effects on VEGFR2 trafficking and signal transduction. ARF6 activation was independently regulated by 2 different ARF GEFs - ARNO and GEP100. Interaction between VEGFR2 and ARNO activated ARF6 and stimulated VEGFR2 internalization, whereas a VEGFR2 interaction with GEP100 activated ARF6 to promote VEGFR2 recycling via coreceptor binding. Intervening in either pathway inhibited VEGFR2 signal output. Finally, using a combination of in vitro, cellular, genetic, and pharmacologic techniques, we demonstrated that ARF6 is pivotal in VEGFR2 trafficking and that targeting ARF6-mediated VEGFR2 trafficking has potential as a therapeutic approach for retinal vascular diseases such as diabetic retinopathy.

Predictors of community-associated Staphylococcus aureus, methicillin-resistant and methicillin-susceptible Staphylococcus aureus skin and soft tissue infections in primary-care settings.

Skin and soft tissue infections (SSTIs) due to Staphylococcus aureus have become increasingly common in the outpatient setting; however, risk factors for differentiating methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) SSTIs are needed to better inform antibiotic treatment decisions. We performed a case-case-control study within 14 primary-care clinics in South Texas from 2007 to 2015. Overall, 325 patients [S. aureus SSTI cases (case group 1, n = 175); MRSA SSTI cases (case group 2, n = 115); MSSA SSTI cases (case group 3, n = 60); uninfected control group (control, n = 150)] were evaluated. Each case group was compared to the control group, and then qualitatively contrasted to identify unique risk factors associated with S. aureus, MRSA, and MSSA SSTIs. Overall, prior SSTIs [adjusted odds ratio (aOR) 7·60, 95% confidence interval (CI) 3·31-17·45], male gender (aOR 1·74, 95% CI 1·06-2·85), and absence of healthcare occupation status (aOR 0·14, 95% CI 0·03-0·68) were independently associated with S. aureus SSTIs. The only unique risk factor for community-associated (CA)-MRSA SSTIs was a high body weight (⩾110 kg) (aOR 2·03, 95% CI 1·01-4·09).

ARF6 Is an Actionable Node that Orchestrates Oncogenic GNAQ Signaling in Uveal Melanoma.

Activating mutations in Gαq proteins, which form the α subunit of certain heterotrimeric G proteins, drive uveal melanoma oncogenesis by triggering multiple downstream signaling pathways, including PLC/PKC, Rho/Rac, and YAP. Here we show that the small GTPase ARF6 acts as a proximal node of oncogenic Gαq signaling to induce all of these downstream pathways as well as ß-catenin signaling. ARF6 activates these diverse pathways through a common mechanism: the trafficking of GNAQ and ß-catenin from the plasma membrane to cytoplasmic vesicles and the nucleus, respectively. Blocking ARF6 with a small-molecule inhibitor reduces uveal melanoma cell proliferation and tumorigenesis in a mouse model, confirming the functional relevance of this pathway and suggesting a therapeutic strategy for Gα-mediated diseases.

Comparison of Vacuum and Aspiration on Phacoemulsification Efficiency and Chatter Using a Monitored Forced Infusion System.

PURPOSE: To evaluate the effect of vacuum and aspiration rates on phacoemulsification efficiency and chatter using a monitored forced infusion system. DESIGN: In vitro animal study. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah. PROCEDURES: Formalin-soaked porcine lenses were divided into 2 mm cubes (tip diameter, 0.9 mm). Vacuum levels were tested at 200, 300, 400, and 500 mm Hg; aspiration rates at 20, 35, and 50 mL/min. Torsional power was set at 60% and intraocular pressure at 50 mm Hg. RESULTS: Increasing vacuum increased efficiency regardless of aspiration rates (R(2) = 0.92; P = .0004). Increasing aspiration further increased efficiency when vacuum was at 400 and 500 mm Hg (P = .004 for 20 vs 35 mL/min, P = .0008 for 35 vs 50 mL/min). At 200 and 300 mm Hg, efficiency only improved when increasing aspiration to 35 mL/min (P < .0001 with 20 vs 35 + 50 mL/min). Chatter improved with increasing vacuum, up to 400 mm Hg (P = .003 for 200 vs 300 mm Hg and P = .045 for 300 vs 500 mm Hg). A similar trend of improved chatter was seen with increasing levels of aspiration. CONCLUSIONS: Vacuum improved efficiency up to 500 mm Hg independent of flow. Flow has an additive effect on efficiency through 50 mL/min, when vacuum is at 400 mm Hg or higher, and only up to 35 mL/min at vacuums less than 400 mm Hg. Chatter correlated with both vacuum and flow such that increasing either parameter decreases chatter, up to 400 mm Hg with vacuum.

Torsional power study using CENTURION phacoemulsification technology.

BACKGROUND: To evaluate the effect of varying levels of power on phacoemulsification efficiency using the CENTURION Vision System. METHODS: Formalin-soaked porcine lenses were divided into 2-mm cubes; 0.9-mm, balanced tips were used. Torsional power levels were tested from 10% to 100% at 10% intervals. Vacuum was set to 550 mmHg, aspiration to 50 ml/min, and intraocular pressure at 50 mmHg. Efficiency (time to lens removal) and chatter (number of lens fragment repulsions from the tip) were determined. RESULTS: Increasing torsional power up to 60% increased efficiency. This effect was linear from 30 to 60% power (R2 = .90; P < 0.05). There were no significant differences in efficiency past 60%. Chatter was highest at 10% power and decreased linearly (R2 = .87; P = 0.007) as power was increased up to 60% power, and chatter did not improve above this power level. CONCLUSIONS: Power improved efficiency only up to a 60% power level, and then was negligible. Chatter correlated well with power up to the 60% level, so that as power was increased, chatter decreased. Because there are no additional benefits in efficiency past 60% power, and because chatter is minimal at 60% power, we recommend torsional ultrasound at 60% as the optimal power setting for using the CENTURION System for phacoemulsification.l.

Moral Identity and Adolescent Prosocial and Antisocial Behaviors: Interactions with Moral Disengagement and Self-regulation.

Moral identity has been positively linked to prosocial behaviors and negatively linked to antisocial behaviors; but, the processes by which it is linked to such outcomes are unclear. The purpose of the present study was to examine moral identity not only as a predictor, but also as a moderator of relationships between other predictors (moral disengagement and self-regulation) and youth outcomes (prosocial and antisocial behaviors). The sample consisted of 384 adolescents (42 % female), ages 15-18 recruited from across the US using an online survey panel. Latent variables were created for moral identity, moral disengagement, and self-regulation. Structural equation models assessed these latent variables, and interactions of moral identity with moral disengagement and self-regulation, as predictors of prosocial (charity and civic engagement) and antisocial (aggression and rule breaking) behaviors. None of the interactions were significant predicting prosocial behaviors. For antisocial behaviors, the interaction between moral identity and moral disengagement predicted aggression, while the interaction between moral identity and self-regulation was significant in predicting aggression and rule breaking. Specifically, at higher levels of moral identity, the positive link between moral disengagement and aggression was weaker, and the negative link between self-regulation and both antisocial behaviors was weaker. Thus, moral identity may buffer against the maladaptive effects of high moral disengagement and low self-regulation.

Proteasome function is required for platelet production.

The proteasome inhibiter bortezomib has been successfully used to treat patients with relapsed multiple myeloma; however, many of these patients become thrombocytopenic, and it is not clear how the proteasome influences platelet production. Here we determined that pharmacologic inhibition of proteasome activity blocks proplatelet formation in human and mouse megakaryocytes. We also found that megakaryocytes isolated from mice deficient for PSMC1, an essential subunit of the 26S proteasome, fail to produce proplatelets. Consistent with decreased proplatelet formation, mice lacking PSMC1 in platelets (Psmc1(fl/fl) Pf4-Cre mice) exhibited severe thrombocytopenia and died shortly after birth. The failure to produce proplatelets in proteasome-inhibited megakaryocytes was due to upregulation and hyperactivation of the small GTPase, RhoA, rather than NF-κB, as has been previously suggested. Inhibition of RhoA or its downstream target, Rho-associated protein kinase (ROCK), restored megakaryocyte proplatelet formation in the setting of proteasome inhibition in vitro. Similarly, fasudil, a ROCK inhibitor used clinically to treat cerebral vasospasm, restored platelet counts in adult mice that were made thrombocytopenic by tamoxifen-induced suppression of proteasome activity in megakaryocytes and platelets (Psmc1(fl/fl) Pdgf-Cre-ER mice). These results indicate that proteasome function is critical for thrombopoiesis, and suggest inhibition of RhoA signaling as a potential strategy to treat thrombocytopenia in bortezomib-treated multiple myeloma patients.