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The removal of introns by the spliceosome is a key gene regulatory mechanism in eukaryotes, with the U1 snRNP subunit playing a crucial role in the early stages of splicing. Studies in metazoans show that the U1 snRNP also conducts splicing-independent functions, but the lack of genetic tools and knowledge about U1 snRNP-associated proteins have limited the study of such splicing-independent functions in plants. Here we describe an RNA-centric approach that identified more than 200 proteins associated with the Arabidopsis U1 snRNP and revealed a tight link to mRNA cleavage and polyadenylation factors. Interestingly, we found that the U1 snRNP protects mRNAs against premature cleavage and polyadenylation within introns-a mechanism known as telescripting in metazoans-while also influencing alternative polyadenylation site selection in 3'-UTRs. Overall, our work provides a comprehensive view of U1 snRNP interactors and reveals novel functions in regulating mRNA 3'-end processing in Arabidopsis, laying the groundwork for understanding non-canonical functions of plant U1 snRNPs., (© 2024. The Author(s).)

Background: Mental and emotional health can affect outcomes after orthopaedic surgery, and patient resilience has been found to be significantly related to postoperative functional outcomes., Purpose: To evaluate the relationship between preoperative patient resilience and 2-year postoperative patient-reported outcomes after rotator cuff repair (RCR). It was hypothesized that patients with low preoperative resilience will have worse patient-reported outcomes at 2 years after RCR versus those with high resilience., Study Design: Cohort study; Level of evidence, 3., Methods: Patients who underwent primary arthroscopic RCR in 2020 at a single institution and completed the Brief Resilience Scale (BRS) preoperatively were identified. Other inclusion criteria were American Shoulder and Elbow Surgeons (ASES) and Single Assessment Numeric Evaluation (SANE) scores at the 2-year follow-up. Outcomes were compared in patients as divided into low resilience (BRS score >1 SD below the mean), normal resilience (BRS score ≤1 SD of the mean), and high resilience (BRS score >1 SD above the mean) groups., Results: Overall, 100 patients (52 male, 48 female; mean age, 60 ± 9 years) were included in this study. Mean BRS scores did not change significantly from preoperative to 2-year follow-up (3.8 ± 0.7 vs 3.9 ± 0.8, P  = .404). All patients had preoperative ASES scores. Low-resilience patients (n = 17) had significantly lower preoperative ASES scores compared with normal (n = 64) and high resilience (n = 19) patients (35 vs 42 vs 54, respectively; P  = .022). There were no significant group differences in postoperative outcomes (revision rate, ASES score, ASES score improvement from preoperative to 2-year follow-up, or SANE score). Multivariate analysis indicated that preoperative resilience was not significantly associated with ASES score improvement (β estimate = -5.64, P  = .150), while resilience at 2-year follow-up was significantly related to ASES score improvement (β estimate = 6.41, P  = .031)., Conclusion: Patient-reported outcomes at 2-year follow-up did not differ based on preoperative patient resilience for arthroscopic RCR patients. Multivariate analysis also showed that preoperative resilience was not associated with improvement in ASES scores; however, resilience at 2-year follow-up was associated with ASES score improvement., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: F.P.T. has received consulting fees from DePuy Synthes/Medical Device Business Services and hospitality payments from Smith+Nephew. K.B.F. has received education payments from Liberty Surgical, consulting fees from Innocoll and Medical Device Business Services, non-consulting fees from Vericel, and honoraria from Vericel. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval for this study was obtained from Thomas Jefferson University (ref No. 19E.943)., (© The Author(s) 2024.)

Ladder-type pentaphenyl chromophores have a rigid, planar π-system and show bright fluorescence featuring pronounced vibrational structure. Such moieties are ideal for studying interchromophoric interactions and delocalization of electronic excitations. We report the synthesis of helical polymers with a rigid square structure based on spiro-linked ladder-type pentaphenyl units. The variation of circular dichroism with increasing chain length provides direct evidence for delocalization of electronic excitations over at least 10 monomeric units. The change in the degree of circular polarization of the fluorescence across the vibronic side bands shows that vibrational motion can localize the excitation dynamically to almost one single unit through breakdown of the Born-Oppenheimer approximation. The dynamic conversion between delocalized and localized excited states provides a new paradigm for interpreting circular dichroism in helical polymers such as proteins and polynucleic acids., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: Previous research exploring the role of race on prostate cancer (PCa) outcomes has demonstrated greater rates of disease progression and poorer overall survival for African American (AA) compared to Caucasian American (CA) men. The current study examines self-reported race as a predictor of long-term PCa outcomes in patients with low and favorable-intermediate risk disease treated with external beam radiation therapy (EBRT)., Methods: This retrospective cohort study examined patients who were consented to enrollment in the Center for Prostate Disease Research Multicenter National Database between January 01, 1990 and December 31, 2017. Men self-reporting as AA or CA who underwent EBRT for newly diagnosed National Comprehensive Cancer Network-defined low or favorable-intermediate risk PCa were included. Dependent study outcomes included: biochemical recurrence-free survival, (ii) distant metastasis-free survival, and (iii) overall survival. Each outcome was modeled as a time-to-event endpoint using race-stratified Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis., Results: Of 840 men included in this study, 268 (32%) were AA and 572 (68%) were CA. The frequency of biochemical recurrence, distant metastasis, and deaths from any cause was 151 (18.7%), 29 (3.5%), and 333 (39.6%), respectively. AA men had a significantly younger median age at time of EBRT and slightly higher biopsy Gleason scores. Multivariable Cox proportional hazards analyses demonstrated no racial differences in any of the study endpoints., Conclusions: These findings reveal no racial disparity in PCa outcomes for AA compared to CA men, in a long-standing, longitudinal cohort of patients with comparable access to cancer care., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Periprosthetic joint infection (PJI) can lead to a severe systemic inflammatory response and may result in systemic sepsis. However, little is known about how often systemic sepsis may occur in patients with PJI, and whether sepsis is associated with a greater likelihood of persistent or recurrent PJI., Questions/purposes: (1) Among patients who present with acute or acute hematogenous PJI and who were treated with debridement, antibiotics, and implant retention (DAIR), what proportion have sepsis and what factors are associated with a presentation with sepsis? (2) For patients presenting with sepsis, what factors are associated with persistent or recurrent PJI?, Methods: In all, 320 patients who underwent DAIR for the treatment of acute postoperative or acute hematogenous PJI between January 2000 and December 2019 were included in this study. Exclusion criteria were patients with other known sources of infection, such as pneumonia or urinary tract infections, which could contribute to systemic sepsis (6% [18 of 320]), patients with chronic PJI, and those with less than 6 months of follow-up (21% [66 of 320]). Our final cohort consisted of 236 patients presenting with an acute postoperative or acute hematogenous PJI who underwent an irrigation and debridement procedure. Sepsis was defined by the criteria for systemic inflammatory response syndrome (SIRS) or bacteria-positive blood culture results. Inclusion of patients with positive blood culture by organisms that caused their joint infection was important as all patients presented with fulminant acute infection of a prosthetic joint. Data, including vital signs, surgical variables, and treatment outcomes, were collected retrospectively through a chart review of an electronic medical record system. The statistical analysis comparing patients with sepsis versus patients without sepsis consisted of logistic regression to identify factors associated with sepsis. After confirming its ability to identify patients with a higher association with the development of sepsis through area under the curve models, a nomogram was generated to standardize our results from the regression, which was supported by the area under the curve model, to help readers better identify patients who are more likely to develop sepsis., Results: A total of 44% (103 of 236) of patients had infections that met the criteria for sepsis. After controlling for confounding variables, including congestive heart failure, anemia, serum C-reactive protein (CRP), and the male sex, it was revealed that serum CRP (odds ratio 1.07 [95% confidence interval 1.04 to 1.11]; p < 0.001) and male sex (OR 1.96 [95% CI 1.03 to 3.81]; p = 0.04) were associated with the development of systemic sepsis. For patients presenting with sepsis, persistent or recurrent PJI were associated with an increased CRP level (OR 1.06 [95% CI 1.02 to 1.11]; p = 0.01) and number of prior surgical procedures on the joint (OR 2.30 [95% CI 1.21 to 4.89]; p = 0.02)., Conclusion: Overall, our findings support that patients with systematic sepsis may benefit from two-stage revision rather than DAIR to decrease the bioburden more effectively, especially in those with methicillin-resistant Staphylococcus aureus and polymicrobial infections. High serum CRP levels and a history of prior surgical procedures on the involved joint should trigger prompt, aggressive surgical treatment if the patient's overall clinical status can tolerate such an intervention., Level of Evidence: Level III, therapeutic study., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2022 by the Association of Bone and Joint Surgeons.)

Background: Both beach-chair and lateral decubitus patient positioning are often utilized for shoulder arthroscopy, with each offering its unique advantages and disadvantages. The surgical position is often selected according to each surgeon's preference, with no clear superiority of one position over the other., Purpose/hypothesis: The purpose was to compare clinical and patient-reported outcomes between patients who underwent arthroscopic posterior labral repair in the beach-chair versus the lateral decubitus position. We hypothesized that patient positioning would not affect clinical and patient-reported outcomes., Study Design: Cohort study; Level of evidence, 3., Methods: A list of all patients diagnosed with the Current Procedural Terminology codes 29806 and 29807 between 2015 and 2019 was obtained from the medical records. Patients were only included if arthroscopic posterior labral repair with or without concomitant superior labral anterior to posterior repair was confirmed. Data collected for eligible patients included the number of anchors used, perioperative and postoperative complications, redislocations, subjective instability, reoperation, and revision. Patients were also contacted to complete several patient-reported outcome surveys. Preoperative data, perioperative data, and postoperative outcomes were compared between patients who underwent surgery in the beach-chair versus lateral decubitus position., Results: Overall, 126 patients were included-69 patients underwent surgery in the lateral decubitus position and 57 in the beach-chair position-with a mean follow-up of 2.6 ± 1.7 years. There were no significant pre- or perioperative differences between groups. Rates of postoperative dislocations, subjective instability, reoperations, revisions, all complications, and return to sports rates also did not differ between groups (all, P > .05). Finally, there was no difference between groups regarding postoperative pain, function, and subjective instability scores (all, P > .05). Results of the multivariate regression analysis showed that increased age was a weak independent risk factor for subjective recurrent posterior shoulder instability (odds ratio, 1.04; P = .036)., Conclusion: Surgical positioning for arthroscopic posterior shoulder labral repair did not affect postoperative clinical and patient-reported outcomes. Both beach-chair and lateral decubitus position provided good outcomes for posterior shoulder labral repair, with an overall recurrence rate of 8.7%. Increased age was a weak independent risk factor for subjective recurrent instability.

Background: Surgical positioning can affect both perioperative and postoperative complication rates. It is unclear whether beach-chair versus lateral decubitus positioning affects outcomes in patients undergoing arthroscopic anterior shoulder stabilization surgery., Purpose: The purpose of this study was to compare recurrent instability, complications, and patient-reported outcomes between patients who underwent arthroscopic anterior shoulder stabilization in the beach-chair versus the lateral decubitus positions. It was hypothesized that recurrent instability, complications, and patient-reported outcomes would not be affected by surgical positioning., Study Design: Cohort study; Level of evidence, 3., Methods: The authors reviewed the medical records of patients who underwent shoulder stabilization ( Current Procedural Terminology codes 29806 and 29807) from 2015 to 2019. Patients were included only if anterior instability was confirmed, arthroscopic surgery was performed in response to shoulder instability, and a minimum of 2 years of follow-up data were available. Data collected for eligible patients included perioperative and postoperative complications, recurrent instability, reoperation, and revision. Patients also completed surveys for the American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE) score, Oxford Shoulder Instability (OSI) score, and a return to any level of sport (RTS) questionnaire., Results: Overall, 294 patients (162 lateral decubitus and 132 beach-chair positions) were included, with an average follow-up of 2.4 ± 1.6 years. There were no significant differences in demographics between groups, nor were there differences in the rates of postoperative dislocations, subjective instability, reoperations, revisions, or complications. There was a trend toward a higher revision rate in the beach-chair group (beach-chair, 6.1% vs lateral decubitus, 1.9%; P = .069). There was no significant difference between groups regarding RTS rates or postoperative ASES, SANE, and OSI scores at 3.3 ± 1.1 years postoperatively., Conclusion: Surgical positioning for arthroscopic anterior shoulder stabilization did not significantly affect recurrent instability, complications, and patient-reported outcomes. Both beach-chair and lateral decubitus positioning provided good outcomes for anterior shoulder stabilization, with an overall recurrent dislocation rate of 7.8% at a mean of 3.3 years after surgery., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: K.B.F. has received education payments from Liberty Surgical, consulting fees from Medical Device Business Services, and speaking fees and honoraria from Vericel. B.J.E. has received research support from Arthrex, DePuy, Linvatec, Smith & Nephew, and Stryker; education payments from Arthrex, DePuy, and Smith & Nephew; and consulting fees from Arthrex. S.H. has received education payments from Liberty Surgical and hospitality payments from Arthrex and Smith & Nephew and has stock/stock options in Johnson & Johnson. M.E.B. has received grant payments from Arthrex, education payments from Arthrex and Smith & Nephew, and hospitality payments from Stryker. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Background: There is ongoing debate on what is optimal prophylactic agent to reduce venous thromboembolism (VTE) following total joint arthroplasty (TJA). Although many studies assess the efficacy of these agents in VTE prevention, no attention is given to their adverse effect on major bleeding events (MBEs). This study compared the incidence of MBE in patients receiving aspirin as VTE prophylaxis vs other chemoprophylaxis., Methods: A single-institution, retrospective study of 35,860 patients undergoing TJA between 2009 and 2020 was conducted. Demographic variables, co-morbidities, type of chemoprophylaxis, and intraoperative factors were collected. MBE was defined using the 2010 criteria for major bleeding in surgical patients presented by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. To enhance capture rate, comprehensive queries utilizing MBE keywords were conducted in clinical notes, physician dictations, and phone call logs. Univariate followed by multivariate regression was performed as well as propensity score matched analysis., Results: Overall, 270 patients (0.75%) in this cohort developed MBE. The MBE rate was 0.5% in the aspirin group and 1.2% in the non-aspirin group. After adjusting for confounders, multiple logistic regression and propensity score matched analysis revealed almost 2 times lower odds of MBE in patients who received aspirin. Variables independently associated with increased MBE risk included increasing age, body mass index, American Society of Anesthesiologists score, revision surgery, peptic ulcer disease, coagulopathy, intraoperative blood transfusion, and active smoking., Conclusion: Administration of aspirin for VTE prophylaxis, compared to other chemoprophylaxis agents may have an association with lower risk of major bleeding following TJA. Future randomized controlled trials should examine these findings., (Copyright © 2021. Published by Elsevier Inc.)

We study the interplay of non-pharmaceutical containment measures, human behavior, and the spread of COVID-19 in Switzerland. First, we collect sub-national data and construct indices that capture the stringency of containment measures at the cantonal level. Second, we use a vector autoregressive model to analyze feedback effects between our variables of interest via structural impulse responses. Our results suggest that increases in the stringency of containment measures lead to a significant reduction in weekly infections as well as debit card transactions, which serve as a proxy for behavioral changes in the population. Furthermore, analyzing different policy measures individually shows that business closures, recommendations to work from home, and restrictions on gatherings have been particularly effective in containing the spread of COVID-19 in Switzerland. Finally, our findings indicate a sizeable voluntary reduction in debit card transactions in response to a positive infection shock., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

Background: The optimal length of aspirin prophylaxis to minimize venous thromboembolism (VTE) following total knee arthroplasty (TKA) remains unknown. This study aimed to determine the timing of VTE after TKA in patients who received low and high dose aspirin, and determine if 30 days of prophylaxis remains adequate., Methods: We retrospectively reviewed records of 9208 patients undergoing primary TKA between 2010 and 2020 who received either low (81 mg twice daily, n = 4413) or high (325 mg twice daily, n = 4795) dose aspirin for VTE prophylaxis. Symptomatic VTEs occurring within 90 days of surgery were identified from medical records and phone call logs. Major bleeding events (MBE) within the first 30 days were also documented. Time to event was recorded., Results: Overall, 88 patients (1.0%) developed symptomatic VTE, with no significant differences in incidence between the low (n = 40, 0.9%) and high (n = 48, 1.0%) dose groups (P = .669). The median time to VTE was 8 days (interquartile range [IQR] 2-15.5), median time to deep vein thrombosis was 12 days (IQR 5-18), and median time to pulmonary embolism was 5 days (IQR 1.5-15). There was a similar distribution in time to VTE in both the low and high dose groups. Aside from a single DVT occurring at day 44, all VTE occurred within 30 days of surgery. During the prophylactic time period, 41 patients (0.4%) developed MBE, which tended to occur more frequently (0.6% vs 0.3%, P = .018) and earlier in the high dose group., Conclusion: Based on the findings, a 30-day low or high dose aspirin regimen remains optimal for prevention of VTE without increasing MBE in TKA patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Neratinib is approved in the European Union for extended adjuvant treatment of human epidermal growth factor receptor 2-positive/hormone receptor-positive (copositive) early breast cancer ≤1 year of completion of prior trastuzumab-based therapy. Here, we report analyses of the hormone receptor-positive subgroup (N = 1631) from the ExteNET trial performed for the German health technology assessment (HTA)., Results: With 2 years of median follow-up, HTA analyses revealed a significant advantage in disease-free survival (DFS) for neratinib vs. placebo (absolute/relative risk reduction: 4.1/48.2%; hazard ratio [HR] [95% confidence interval {CI}]: 0.45 [0.29; 0.69]; p = 0.0002), consistent with distant DFS (absolute/relative risk reduction: 3.1/46.3%; HR [95% CI]: 0.52 [0.32; 0.84]; p = 0.0082). The 5-year follow-up confirmed this outcome.Quality of life analyses did not show clinically relevant differences over all time points. Only at month 1, the Functional Assessment of Cancer Therapy - General total score revealed a statistically relevant difference to the disadvantage of neratinib classified as clinically relevant. The tolerability profile of neratinib was dominated by gastrointestinal events, mainly diarrhoea (all grades: 94.4%; grade III: 39.4%; no systematic antidiarrhoeal prophylaxis), nausea (all grades/grade III: 43.9/1.6%), vomiting (26.6/3.2%), abdominal pain (23.8/1.9%), fatigue (28.1/1.9%) and rash (14.3/0.4%). No cumulative or irreversible toxicities were observed. As shown in the CONTROL study and instituted via a risk management plan, diarrhoea management can reduce frequency, cumulative duration and severity of diarrhoea., Conclusion: Extended adjuvant neratinib provides a clinically relevant benefit with further incremental reduction of relapse risk in the curative setting. Accordingly, the German HTA authority has granted an added benefit for this new treatment option., Competing Interests: Conflict of interest statement D.L. received consulting fees from Pierre Fabre, AstraZeneca, Novartis, Eli Lilly, Pfizer, Celgene, L'Oreal, Teva, Tesaro and Amgen as well as fees for non-CME services (e.g. speakers' bureaus) from Pierre Fabre, AstraZeneca, Novartis, Eli Lilly, Pfizer, Celgene, L'Oreal, Teva, Tesaro and Amgen. H.T. received consulting fees from Pierre Fabre, Pfizer Pharma GmbH, Mundipharma, ClinSol, Novartis, Lilly, Grünenthal, Vifor, AstraZeneca and Mylan. M.S. received honoraria for the speaker or consultancy role from AMGEN, AstraZeneca, Eisai, Lilly, Myelo Therapeutics, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche and Seattle Genetics. He received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Myelo Therapeutics, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre and Roche. He received travel reimbursement from Pfizer and Roche. A.D.H. received consulting fees from Roche, Novartis, Teva, Pfizer, AstraZeneca, Eisai, Hexal, Genomic Health, Lilly, MSD and Pierre Fabre as well as fees for non-CME services (e.g. speakers' bureaus) from Roche, Novartis, Teva, Pfizer, AstraZeneca, Lilly and MSD. N.H. received consulting fees from Pierre Fabre and Roche. S.S. is an employee at AMS Advanced Medical Services GmbH, München, Germany; A.R., L.G. and C.R. are employees at Pierre Fabre Pharma GmbH, Freiburg, Germany, and R.V. is an employee at Pierre Fabre Médicament, Boulogne-Billancourt, France., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The Monte Carlo simulation of light propagation in optical systems requires the processing of a large number of photons to achieve a satisfactory statistical accuracy. Based on classical Mie scattering, we experimentally show that the independence of photons propagating through a turbid medium imposes a postulate for a concurrent and scalable programming paradigm of general purpose graphics processing units. This ensures that, without rewriting code, increasingly complex optical systems can be simulated if more processors are available in the future.

The hippocampus is essential for the formation and retrieval of memories and is a crucial neural structure sub-serving complex cognition. Adult hippocampal neurogenesis, the birth, migration and integration of new neurons, is thought to contribute to hippocampal circuit plasticity to augment function. We evaluated hippocampal volume in relation to brain volume in 375 mammal species and examined 71 mammal species for the presence of adult hippocampal neurogenesis using immunohistochemistry for doublecortin, an endogenous marker of immature neurons that can be used as a proxy marker for the presence of adult neurogenesis. We identified that the hippocampus in cetaceans (whales, dolphins and porpoises) is both absolutely and relatively small for their overall brain size, and found that the mammalian hippocampus scaled as an exponential function in relation to brain volume. In contrast, the amygdala was found to scale as a linear function of brain volume, but again, the relative size of the amygdala in cetaceans was small. The cetacean hippocampus lacks staining for doublecortin in the dentate gyrus and thus shows no clear signs of adult hippocampal neurogenesis. This lack of evidence of adult hippocampal neurogenesis, along with the small hippocampus, questions current assumptions regarding cognitive abilities associated with hippocampal function in the cetaceans. These anatomical features of the cetacean hippocampus may be related to the lack of postnatal sleep, causing a postnatal cessation of hippocampal neurogenesis.

Patients from traditionally underrepresented communities need to be involved in discussions around genomics research including attitudes towards participation and receiving personal results. Structured interviews, including open-ended and closed-ended questions, were conducted with 205 patients in an inner-city hospital outpatient clinic: 48 % of participants self-identified as Black or African American, 29 % Hispanic, 10 % White; 49 % had an annual household income of <$20,000. When the potential for personal results to be returned was not mentioned, 82 % of participants were willing to participate in genomics research. Reasons for willingness fell into four themes: altruism; benefit to family members; personal health benefit; personal curiosity and improving understanding. Reasons for being unwilling fell into five themes: negative perception of research; not personally relevant; negative feelings about procedures (e.g., blood draws); practical barriers; and fear of results. Participants were more likely to report that they would participate in genomics research if personal results were offered than if they were not offered (89 vs. 62 % respectively, p < 0.001). Participants were more interested in receiving personal genomic risk results for cancer, heart disease and type 2 diabetes than obesity (89, 89, 91, 80 % respectively, all p < 0.001). The only characteristic consistently associated with interest in receiving personal results was disease-specific worry. There was considerable willingness to participate in and desire for personal results from genomics research in this sample of predominantly low-income, Hispanic and African American patients. When returning results is not practical, or even when it is, alternatively or additionally providing generic information about genomics and health may also be a valuable commodity to underrepresented minority and other populations considering participating in genomics research.

Background: New genetic associations with obesity are rapidly being discovered. People's causal beliefs about obesity may influence their obesity-related behaviors. Little is known about genetic compared to lifestyle causal beliefs regarding obesity, and obesity-related diseases, among minority populations. This study examined genetic and lifestyle causal beliefs about obesity and 3 obesity-related diseases among a low-income, ethnically diverse patient sample., Methods: Structured interviews were conducted with patients attending an inner-city hospital outpatient clinic. Participants (n=205) were asked how much they agreed that genetics influence the risk of obesity, type 2 diabetes, heart disease, and cancer. Similar questions were asked regarding lifestyle causal beliefs (overeating, eating certain types of food, chemicals in food, not exercising, smoking). In this study, 48% of participants were non-Hispanic Black, 29% Hispanic and 10% non-Hispanic White., Results: Over two-thirds (69%) of participants believed genetics cause obesity 'some' or 'a lot', compared to 82% for type 2 diabetes, 79% for heart disease and 75% for cancer. Participants who held genetic causal beliefs about obesity held more lifestyle causal beliefs in total than those who did not hold genetic causal beliefs about obesity (4.0 vs. 3.7 lifestyle causal beliefs, respectively, possible range 0-5, p=0.025). There were few associations between causal beliefs and sociodemographic characteristics., Conclusions: Higher beliefs in genetic causation of obesity and related diseases are not automatically associated with decreased lifestyle beliefs. Future research efforts are needed to determine whether public health messages aimed at reducing obesity and its consequences in racially and ethnically diverse urban communities may benefit from incorporating an acknowledgement of the role of genetics in these conditions., (Copyright © 2012 S. Karger AG, Basel.)

Body temperature (T(b)) is an important physiological component that affects endotherms from the cellular to whole organism level, but measurements of T(b) in the field have been noticeably skewed towards heterothermic species and seasonal comparisons are largely lacking. Thus, we investigated patterns of T(b) patterns in a homeothermic, free-ranging small mammal, the Damaraland mole-rat (Fukomys damarensis) during both the summer and winter. Variation in T(b) was significantly greater during winter than summer, and greater among males than females. Interestingly, body mass had only a small effect on variation in T(b) and there was no consistent pattern relating ambient temperature to variation in T(b). Generally speaking, it appears that variation in T(b) patterns varies between seasons in much the same way as in heterothermic species, just to a lesser degree. Both cosinor analysis and Fast Fourier Transform analysis revealed substantial individual variation in T(b) rhythms, even within a single colony. Some individuals had no T(b) rhythms, while others appeared to exhibit multiple rhythms. These data corroborate previous laboratory work showing multiplicity of rhythms in mole-rats and suggest the variation seen in the laboratory is a true indicator of the variation seen in the wild.

Purpose: An in vitro dye-penetration study was performed on 2 different self-etching adhesives (Prompt L-Pop II, 3M-Espe; NRC, Prime&Bond NT Quix, Dentsply/DeTrey) in comparison to conventional conditioning of the cavity with phosphoric acid (Conditioner 36, P&B NT Quix, Dentsply/DeTrey)., Materials and Methods: Standardized mod cavities (one cervical margin in cementum, one in enamel) were prepared in 80 extracted human teeth (n = 20/group). Prompt L-Pop II was employed in two different sequences: A: placing the matrix band first, then applying the adhesive, B: first applying the adhesive, then placing the matrix band. The adhesive was cured in both cases. Conditioning and application of P&B NT Quix was carried out after placement of the matrix band in both procedures. The compomer Dyract AP was used as a restorative material in all cavities. After thermocycling, the median percentages of dye-penetrated (2% methylene blue) margins were determined separately for the cementum and enamel margins of the approximal boxes and for the lateral enamel margins of the boxes., Results: The results showed that when using Prompt L-Pop II in Class II cavities, the adhesive should be applied before placing the matrix band (p < 0.0001). When the matrix band was placed first, P&B NT Quix showed superior results at a statistically significant level (p < 0.0001) in comparison to Prompt L-Pop II. There was no significant difference in the use of P&B NT Quix in combination with NRC or phosphoric acid in these Class II cavities., Conclusion: It is strongly recommended that Prompt L-Pop be applied prior to placement of the matrix band. Prime & Bond NT Quix seems to provide clinically relevant marginal seal in Class II cavities, regardless of whether NRC or phosphoric acid is used for conditioning.

To evaluate the role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in breast cancer cell survival and therapeutic resistance, we analyzed a panel of six breast cancer cell lines that varied in erbB2 and estrogen receptor status. Akt activity was constitutive in four cell lines and was associated with either PTEN mutations or erbB2 overexpression. Akt promoted breast cancer cell survival because a PI3K inhibitor, LY294002, or transient transfection of a dominant-negative Akt mutant inhibited Akt activity and increased apoptosis. When combined with therapies commonly used in breast cancer treatment, LY294002 potentiated apoptosis caused by doxorubicin, trastuzumab, paclitaxel, or etoposide. Potentiation of apoptosis by LY294002 correlated with induction of Akt by doxorubicin or trastuzumab alone that occurred before the onset of apoptosis. Similar results were observed with tamoxifen. Combining LY294002 with tamoxifen in estrogen receptor-positive cells greatly potentiated apoptosis, which was correlated with tamoxifen-induced Akt phosphorylation that preceded apoptosis. To confirm that the effects of LY294002 on chemotherapy-induced apoptosis were attributable to inhibition of Akt, we transiently transfected breast cancer cells with dominant-negative Akt and observed increased doxorubicin-induced apoptosis. Conversely, stably transfecting cells with constitutively active Akt increased Akt activity and attenuated doxorubicin-induced apoptosis. These studies show that endogenous Akt activity promotes breast cancer cell survival and therapeutic resistance, and that induction of Akt by chemotherapy, trastuzumab, or tamoxifen might be an early compensatory mechanism that could be exploited to increase the efficacy of these therapies.

Glutamine synthetase (GS; EC 6.3.1.2) from Streptomyces cattleya was purified using a single affinity-gel chromatography step, and some of its properties were determined. Levels of GS in S. cattleya cells varied by a factor of 8 depending upon the source of nitrogen in the growth medium. Of 24 nitrogen sources examined only glutamine or NH4Cl utilization resulted in very low GS activity. Addition of NH4Cl to a culture with high GS levels appeared to stop further synthesis and resulted in a progressive decrease in the specific activity of the enzyme. The GS inhibitor methionine sulphoximine (MSX) inhibited GS activity but had no effect on exponentially growing cells. The presence of MSX either lengthened or shortened the period between spore inoculation and initiation of exponential growth, depending on the source of nitrogen. In glutamine minimal medium MSX produced earlier and more efficient spore germination while in glutamate or nitrate minimal medium germination was delayed by its presence.

Mutations causing constitutive synthesis of glutamine synthetase (GlnC(-) phenotype) were transferred from Klebsiella aerogenes into Klebsiella pneumoniae by P1-mediated transduction. Such GlnC(-) strains of K. pneumoniae have constitutive levels of glutamine synthetase. Two of three GlnC(-) strains of K. pneumoniae studied, each containing independently isolated mutations that confer the GlnC(-) phenotype, continue to synthesize nitrogenase in the presence of NH(4) (+). One strain, KP5069, produces 30% as much nitrogenase when grown in the presence of 15 mM NH(4) (+) as in its absence. The GlnC(-) phenotype allows the synthesis of nitrogenase to continue under conditions that completely repress nitrogenase synthesis in the wild-type strain. Glutamine auxotrophs of K. pneumoniae, that do not produce catalytically active glutamine synthetase, are unable to synthesize nitrogenase during nitrogen limited growth. Complementation of K. pneumoniae Gln(-) strains by an Escherichia coli episome (F'133) simultaneously restores glutamine synthetase activity and the ability to synthesize nitrogenase. These results indicate a role for glutamine synthetase as a positive control element for nitrogen fixation in K. pneumoniae.

We used polyacrylamide gel electrophoresis to examine the regulation and adenylylation states of glutamine synthetases (GSs) from Escherichia coli (GS(E)) and Klebsiella aerogenes (GS(K)). In gels containing sodium dodecyl sulfate (SDS), we found that GS(K) had a mobility which differed significantly from that of GS(E). In addition, for both GS(K) and GS(E), adenylylated subunits (GS(K)-adenosine 5'-monophosphate [AMP] and GS(E)-AMP) had lesser mobilities in SDS gels than did the corresponding non-adenylylated subunits. The order of mobilities was GS(K)-AMP < GS(K) < GS(E)-AMP < GS(E). We were able to detect these mobility differences with purified and partially purified preparations of GS, crude cell extracts, and whole cell lysates. SDS gel electrophoresis thus provided a means of estimating the adenylylation state and the quantity of GS present independent of enzymatic activity measurements and of determining the strain origin. Using SDS gels, we showed that: (i) the constitutively produced GS in strains carrying the glnA4 allele was mostly adenylylated, (ii) the GS-like polypeptide produced by strains carrying the glnA51 allele was indistinguishable from wild-type GS(K), and (iii) strains carrying the glnA10 allele contained no polypeptide having the mobility of GS(K) or GS(K)-AMP. Using native polyacrylamide gels, we detected the increased amount of dodecameric GS present in cells grown under nitrogen limitation compared with cells grown under conditions of nitrogen excess. In native gels there was neither a significant difference in the mobilities of adenylylated and non-adenylylated GSs nor a GS-like protein in cells carrying the glnA10 allele.