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Physicians groups hailed a new federal rule requiring health insurers to streamline and disclose more information about their prior authorization processes, saying it will improve patient care and reduce doctors' [...]

The present study examines the role of irritability in form and function subtypes of aggression over 1 year in early childhood (N= 300, Mage= 44.70 months, SD= 4.38 months). This study prospectively tests hostile attribution biases (HAB) as a mediator in irritability’s relations with aggression, with hypothesized form-specific relations between HAB and aggression. Moderation by gender and a reversed alternative model (aggression to irritability, mediated by HAB), were also tested. Path analyses showed irritability predicted increases in all subtypes of aggression (βs = 0.24–0.34), but with moderation by gender, such that irritability significantly predicted increases in reactive relational aggression for girls only (β = 0.43). Reactive physical aggression also significantly predicted increases in irritability (β = 0.15). HAB was not associated significantly with any forms or functions of aggression, although gender differences emerged between HAB for instrumental provocations and reactive physical aggression. No significant indirect effects were found. Results highlight the importance of considering both forms and functions of aggression when investigating irritability, and point to potential gender differences in the role of irritability in relational aggression in early childhood.

Coronaviruses have caused three major epidemics since 2003, including the ongoing SARS-CoV-2 pandemic. In each case, the emergence of coronavirus in our species has been associated with zoonotic transmissions from animal reservoirs1,2, underscoring how prone such pathogens are to spill over and adapt to new species. Among the four recognized genera of the family Coronaviridae, human infections reported so far have been limited to alphacoronaviruses and betacoronaviruses3–5. Here we identify porcine deltacoronavirus strains in plasma samples of three Haitian children with acute undifferentiated febrile illness. Genomic and evolutionary analyses reveal that human infections were the result of at least two independent zoonoses of distinct viral lineages that acquired the same mutational signature in the genes encoding Nsp15 and the spike glycoprotein. In particular, structural analysis predicts that one of the changes in the spike S1 subunit, which contains the receptor-binding domain, may affect the flexibility of the protein and its binding to the host cell receptor. Our findings highlight the potential for evolutionary change and adaptation leading to human infections by coronaviruses outside of the previously recognized human-associated coronavirus groups, particularly in settings where there may be close human–animal contact.

A replication of a preventive early childhood intervention study for reducing relational and physical aggression and peer victimization was conducted (Ostrov et al., 2009). The present study expanded on the original 6-week program, and the revised Early Childhood Friendship Project (ECFP) 8-week program consisted of developmentally appropriate puppet shows, active participatory activities, passive activities, and in vivo reinforcement periods. Both teacher and observer reports were obtained at pretest and posttest for relational and physical bullying, as well as relational and physical peer victimization, for each participating child. The initial sample (N = 141; age M = 45.53 months; age SD = 7.29) included 80 children randomly assigned to the intervention group (six classrooms) and 61 children randomly assigned to the control group (six classrooms). The present study found that the ECFP reduced relational bullying in the intervention group relative to the control group and reduced relational and physical victimization for girls in the intervention group relative to the control group. The importance of early intervention and implications for educators and clinicians are discussed., A developmental psychopathology perspective emphasizes the importance of early childhood peer relationships and the skills acquired during this key developmental period for setting the stage for later peer interactions and [...]

An interview with Joel Ostrov, President of Direct Travel, is presented. Topics include Ostrov is cautious about economic headwinds such as inflation and rising mortgage rates but believes that Direct Travel; and opportunity for Direct Travel lies in its value proposition to ease travel burdens for clients amid the chaotic airline environment for the future of the travel industry.

Study Design Systematic review and meta-analysis.Objectives Determine if tobacco use is associated with increased risk of postoperative adverse events within 90 days in patients undergoing spinal fusion surgery.Methods Databases were queried to identify cohort studies that directly compared smokers with non-smokers and provided the absolute number of adverse events and the population at risk. Data quality was evaluated using the Quality in Prognosis Studies tool. Risk ratios (RR) and 95% confidence intervals were calculated and compared between studies. The grading of recommendation, assessment, development and evaluation (GRADE) criteria were used to assess the strength of the evidence.Results Seventeen studies assessing 37 897 participants met the inclusion criteria. Of these, 10 031 (26.5%) were smokers and 27 866 (73.5%) were nonsmokers. The mean age for the study population was 58 years, and 45% were males. Smoking was not associated with increased risk of one or more major adverse events within 90 days following spine surgery (seven studies, pooled RR 1.13, 95% CI [.75-1.71], I2 = 41%). However, smoking was significantly associated with one or more major adverse events in ≤2 level fusion (three studies, pooled RR 2.46, 95% CI [1.18-5.12], I2 = 0%), but not in fusions of ≥3 levels (four studies, pooled RR .87, 95% CI [.70-1.08], I2 = 0%). Additionally, there was no statistically significant association between smoking and any adverse event, nor increased reoperation risk due to adverse events.Conclusions In this meta-analysis, tobacco use was not associated with a statistically significant increased risk of adverse events within 90 days in patients undergoing spinal fusion surgery. Our results are limited by the variable reporting methodology for both complication rates as well as smoking incidence between the included individual studies.

Little research has used in vivo, naturalistic observations to understand developmental processes related to bullying in early childhood. To test associations between how young children respond to experiences of peer victimization and changes in relational and physical bullying behaviors, a short-term longitudinal study using behavioral observations and teacher reports was conducted among 164 (84 females) preschool children (M= 47.76 months, SD= 7.41). Findings indicated that observed aggressive responses to school-based peer victimization was significantly associated with increases in teacher-reported relational bullying across the academic year. In addition, observed teacher reactions to peer victimization were significantly associated with increases in relational bullying across the academic year. The ways in which these findings extend the literature are discussed.

Abstract. The school classroom and playground provide an important context for learning about young children's social interactions. A multimethod, multiinformant, short-term longitudinal study was conducted to investigate the utility of [...]

The pathophysiology of gout is well-understood, but the disease continues to be misdiagnosed and consequently both undertreated and overtreated. Correct diagnosis is imperative, however, because most of the drugs available [...]

President-elect Donald Trump's nominations for key health agencies have sparked controversy and mixed reactions. The nominations include Martin A. Makary, MD, MPH, for the FDA, David J. Weldon, MD, for the CDC, and Janette Nesheiwat, MD, for surgeon general. Makary, known for his work in patient safety and criticism of federal COVID-19 response, has drawn both praise and criticism. Nesheiwat, a vocal advocate for preventive medicine, has faced scrutiny for her views on COVID mandates and vaccines. Weldon, a former congressman, has raised concerns about vaccine safety, leading to divided opinions on his nomination. [Extracted from the article]

Study Design Systemic review and meta-analysis.Objective To review and establish the effect of tobacco smoking on risk of nonunion following spinal fusion.Methods A systematic search of Medline, Embase, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from inception to December 31, 2020, was conducted. Cohort studies directly comparing smokers with nonsmokers that provided the number of nonunions and fused segments were included. Following data extraction, the risk of bias was assessed using the Quality in Prognosis Studies Tool, and the strength of evidence for nonunion was evaluated using the GRADE working group criteria. All data analysis was performed in Review Manager 5, and a random effects model was used.Results Twenty studies assessing 3009 participants, which included 1117 (37%) smokers, met inclusion criteria. Pooled analysis found that smoking was associated with increased risk of nonunion compared to not smoking ≥1 year following spine surgery (RR 1.91, 95% CI 1.56 to 2.35). Smoking was significantly associated with increased nonunion in those receiving either allograft (RR 1.39, 95% CI 1.12 to 1.73) or autograft (RR 2.04, 95% CI 1.54 to 2.72). Both multilevel and single level fusions carried increased risk of nonunion in smokers (RR 2.30, 95% CI 1.64 to 3.23; RR 1.79, 95% CI 1.12 to 2.86, respectively).Conclusion Smoking status carried a global risk of nonunion for spinal fusion procedures regardless of follow-up time, location, number of segments fused, or grafting material. Further comparative studies with robust methodology are necessary to establish treatment guidelines tailored to smokers.

Doctors treating patients with weakened immune systems and muscle pain and swelling may need to consider a diagnosis of pyomyositis. Pyomyositis is an infection of skeletal muscles, usually occurring in tropical climates. Researchers describe the cases of three patients diagnosed with pyomyositis in temperate climates. One had insulin-dependent diabetes mellitus, another had chicken pox complicated by a streptococcal infection, and another had sickle cell anemia. Symptoms included fever, achiness, high white cell count, and tender muscles. Pyomyositis can be effectively treated with antibiotics and drainage of abscesses.

Study Design: Retrospective cohort study.Objective: To identify disparities in surgical decision making for lumbar disc pathologies based on patient demographics, hospital characteristics, and temporal characteristics of admission.Methods: A retrospective analysis of patients admitted for surgical intervention of disc herniation or degeneration was performed to observe the effect of demographic, hospital, and admission-related factors on the decision to perform an isolated decompression or decompression with single level fusion using the National Inpatient Sample.Results: Of 84 953 patients with lumbar disc pathologies, 69 975 patients were treated electively, and 14 978 patients were treated nonelectively. Hispanic and Asian/Pacific Islander patients were less likely to receive a fusion for elective cases compared with White patients (odds ratio [OR] 0.88, P= .004; OR 0.70, P< .001, respectively). In elective cases, privately insured and self-paying patients were less likely to receive a fusion compared with Medicare patients (OR 0.83, P< .001; OR 0.66, P< .001, respectively), while this effect was limited to self-pay patients in nonelective cases (OR 0.44, P< .001). Urban teaching and nonteaching hospitals were less likely to perform fusions compared with rural hospitals in nonelective cases (OR 0.47, P< .001; OR 0.58, P< .001, respectively). Private for-profit hospitals were associated with higher rates of fusion in both elective and nonelective cases (OR 1.16, P= .003; OR 1.94, P< .001).Conclusion: This study illustrates disparities in the modality of surgical intervention for lumbar disc pathologies in terms of demographics, hospital characteristics, and temporal characteristics of admission. The development of more evidence-based guidelines is warranted to reduce variability seen in treatment regimens for these conditions.

Septic arthritis is an arthritic condition that arises from infection of synovial (joint) tissues by bacteria or other agents. A case is described of a 49-year-old man who had a condition that mimicked septic arthritis, but was caused by neuropathic arthropathy, a joint disorder in which nerve damage and loss of sensation lead to overuse and repetitive joint injury. The patient had syringomyelia, a fluid-filled cavity within the spinal cord, which contributed to tingling and numbness in the hand, numbness and weakness in the arm, and muscle atrophy. Neuropathic arthropathy occurs in up to 30 percent of patients with syringomyelia, most often involving the shoulder. Diagnosis of the joint problem was delayed by seven months, as the shoulder swelling, although massive, was painless. Many details of this patient's case are typical. Severe destruction of the shoulder developed rapidly, within one month. Neuropathic arthropathy involving the shoulder is thought to involve nerve loss, which then leads to decreased blood flow to bone, and bone resorption (loss of calcium and bone structure). The case is unusual, however, regarding the high level of inflammation and high numbers of white blood cells that were present in the synovial fluid. Bacterial infections were ruled out. This type of inflammatory phase may be a more common feature of early neuropathic arthropathy than realized. Alternatively, it might have been provoked by high synovial fluid levels of fat particles, possibly generated from red blood cells or the breakdown of bone marrow. (Consumer Summary produced by Reliance Medical Information, Inc.)

An overview on the process and methodology that should followed while planning for a peak season is presented, with reference to the process followed by Conagra Foods Retail.

Microbicides, which come from seaweeds or first-generation AIDS drugs are being used in gels or creams that can be applied vaginally or rectally to help in preventing AIDS. Clinical trials are being conducted in India to check the most promising AIDS prevention methods but researchers are frustrated by the long bureaucratic and scientific delays in using these gels on a much larger scale.

An interview with Joel Ostrov president of Direct Travel is presented. Topics include he talks about the impact of COVID-19 on the Canadian travel business, he discusses how Direct Travel is managing its way through the pandemic, and how Travel Management Companies (TMCs) are reassuring their team members that things will improve.

The article presents an interview with Joel Ostrov, President – Canada East, Direct Travel. Ostrov offers a cautiously optimistic forecast for the travel industry in 2024, highlighting the resilience of vacation travel, the impact of geopolitical events, and the role of Artificial Intelligence in shaping travel experiences and business strategies.

Epithelial barrier loss is a driver of intestinal and systemic diseases. Myosin light chain kinase (MLCK) is a key effector of barrier dysfunction and a potential therapeutic target, but enzymatic inhibition has unacceptable toxicity. Here, we show that a unique domain within the MLCK splice variant MLCK1 directs perijunctional actomyosin ring (PAMR) recruitment. Using the domain structure and multiple screens, we identify a domain-binding small molecule (divertin) that blocks MLCK1 recruitment without inhibiting enzymatic function. Divertin blocks acute, tumor necrosis factor (TNF)-induced MLCK1 recruitment as well as downstream myosin light chain (MLC) phosphorylation, barrier loss, and diarrhea in vitro and in vivo. Divertin corrects barrier dysfunction and prevents disease development and progression in experimental inflammatory bowel disease. Beyond applications of divertin in gastrointestinal disease, this general approach to enzymatic inhibition by preventing access to specific subcellular sites provides a new paradigm for safely and precisely targeting individual properties of enzymes with multiple functions.

A biography of Fanny Burney, who turned 18th-century taste for gossip into a career as a fiction writer. FANNY BURNEY A Biography. By Claire Harman. Illustrated. 417 pp. New York: [...]

A new federal rule requiring health insurers to streamline and disclose more information about their prior authorization processes has been hailed as a "major win" for patients and doctors. The rule, released by the Centers for Medicare & Medicaid Services, requires insurers to respond to expedited prior authorization requests within 72 hours and other requests within 7 days. Insurers must also publicly release data on denial and approval rates for medical treatment and provide patients with more information about their decisions to deny care. The rule aims to reduce the administrative burden on doctors and improve patient care. [Extracted from the article]

Giant cell arteritis (GCA) is a chronic granulomatous vasculitis of medium and large arteries leading to cranial and extracranial manifestations. Temporal artery biopsy is considered the gold standard; however, its sensitivity is low at 47%. We report a unique case of Bing–Neel Syndrome (BNS) presenting as biopsy-proven GCA. BNS is a rare complication (1%) of Waldenstrom Macroglobulinemia (WM), which results from infiltration of lymph plasmacytoid cells and plasma cells into the central nervous system. A 77-year-old female with a past medical history of glaucoma, hypertension, diabetes, and chronic ocular ischemic syndrome in her right eye presented with progressive left eye vision loss for 5?days. Fundoscopic examination was notable for pseudophakic pseudopallor but no optic disc edema. Intraocular pressure was >40 and normalized after acetazolamide. The patient was started on pulse dose steroids by her neuro-ophthalmologist. She was discharged home on 60?mg of prednisone. At follow up with her neuro-ophthalmologist, new dot blot hemorrhages in the left eye were noted and she was readmitted for pulse dose of intravenous methylprednisolone. Temporal artery biopsy was consistent with GCA spectrum. Work up revealed paraproteinemia and subsequent bone marrow biopsy demonstrated WM. The patient was treated for her WM and her ophthalmic complications stabilized.

In the recently published article “Emotions and Cognitions in Early Childhood Aggression: the Role of Irritability and Hostile Attribution Biases” Figure captions (under Figs. 1 and 2) and notes within the figures are redundant. These notes should be deleted.

Often misdiagnosed, gout is identified by key clinical findings and associated conditions. Although drug therapy is effective, it may also have toxic side effects. The pathophysiology of gout is well-understood, [...]

Severe adverse drug reactions are a common cause of morbidity and mortality. Some of the most severe reactions are immunologically mediated and have been linked to specific HLA alleles. The mechanisms underlying HLA-associated drug hypersensitivity are complex and not fully understood. Recent findings have provided insight into recognition mechanisms underlying drug-induced immunopathogenesis and criteria for increasing positive prediction of hypersensitivity. Refining pharmocogenetic testing strategies to better identify at-risk individuals can improve hypersensitivity prevention and mechanism characterization.

ABSTRACTMelanoma is one of the fastest growing cancers in the United States and is accompanied with a poor prognosis owing to tumors being resistant to most therapies. Atypical protein kinase Cs (aPKC) are involved in malignancy in many cancers. We previously reported that aPKCs play a key role in melanoma's cell motility by regulating cell signaling pathways which induce epithelial-mesenchymal Transition (EMT). We tested three novel inhibitors; [4-(5-amino-4-carbamoylimidazol-1-yl)-2,3-dihydroxycyclopentyl] methyl dihydrogen phosphate (ICA-1T) along with its nucleoside analog 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide (ICA-1S) which are specific to protein kinase C-iota (PKC-ι) and 8-hydroxy-1,3,6-naphthalenetrisulfonic acid (ζ-Stat) which is specific to PKC-zeta (PKC-ζ) on cell proliferation, apoptosis, migration and invasion of two malignant melanoma cell lines compared to normal melanocytes. Molecular modeling was used to identify potential binding sites for the inhibitors and to predict selectivity. Kinase assay showed >50% inhibition for specified targets beyond 5 μM for all inhibitors. Both ICA-1 and ζ-Stat significantly reduced cell proliferation and induced apoptosis, while ICA-1 also significantly reduced migration and melanoma cell invasion. PKC-ι stimulated EMT via TGFβ/Par6/RhoA pathway and activated Vimentin by phosphorylation at S39. Both ICA-1 and ζ-Stat downregulate TNF-α induced NF-κB translocation to the nucleus there by inducing apoptosis. Results suggest that PKC-ι is involved in melanoma malignancy than PKC-ζ. Inhibitors proved to be effective under in-vitroconditions and need to be tested in-vivofor the validity as effective therapeutics. Overall, results show that aPKCs are essential for melanoma progression and metastasis and that they could be used as effective therapeutic targets for malignant melanoma.

Heart attack patients whose ambulances were diverted from crowded emergency departments to hospitals farther away were more likely to be dead a year later than patients who weren't diverted, according [...]

Hepatocellular carcinoma (HCC) has a high morbidity and mortality rate worldwide, with limited treatment options. Glypican-3 (GPC3) is a glycosylphosphatidylinositol-anchored glycoprotein that is overexpressed in most HCC tissues but not in normal tissues. GPC3-targeting antibody therapy shows limited response in a clinical trial due to the lack of a tumor-specific cytotoxic T lymphocyte (CTL) response. Here, in C57/B6 mice, we demonstrated that intravenous infusion of GPC3-coupled lymphocytes (LC/GPC3+) elicited robust GPC3-specific antibody and CTL responses, which effectively restricted proliferation and lysed cultured-HCC cells. Treatment with LC/GPC3+induced durable tumor regression in HCC-bearing C57/B6 mice. Administration of LC/GPC3+induced elevated levels of the cytotoxic T cell bioactive factors tumor necrosis factor alpha (TNF-α), interferon-γ (IFN-γ), granzyme B, and perforin, and substantially increased the number of infiltrating CD8+T cells in tumor tissues. Moreover, immune responses elicited by LC/GPC3+selectively suppressed GPC3+tumors, but didn’t affect the GPC3−tumors in BALB/c mice. Our findings provide the first preclinical evidence that intravenous infusion of the LC/GPC3+complex can induce a strong anti-HCC effect through regulating systemic and local immune responses. These results indicate that the LC/GPC3+complex could be developed as precision therapeutics for HCC patients in the future.

Autoantibodies recognizing 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) are associated with statin exposure, the HLA allele DRB1*11:01, and necrotizing muscle biopsies in adult myositis patients. The aim of this study was to characterize the features of juvenile anti‐HMGCR‐positive myositis patients. The sera of 440 juvenile myositis patients were screened for anti‐HMGCR autoantibodies. Demographic and clinical features, responses to therapy, and HLA alleles were assessed. The features of anti‐HMGCR‐positive patients were compared to those of previously described adult patients with this autoantibody and to children with other myositis‐specific autoantibodies (MSAs). Five of 440 patients (1.1%) were anti‐HMGCR‐positive; none had taken statin medications. Three patients had rashes characteristic of juvenile dermatomyositis and 2 patients had immune‐mediated necrotizing myopathies. The median highest creatine kinase (CK) level of anti‐HMGCR‐positive subjects was 17,000 IU/liter. All patients had severe proximal muscle weakness, distal weakness, muscle atrophy, joint contractures, and arthralgias, which were all more prevalent in HMGCR‐positive subjects compared to MSA‐negative patients or those with other MSAs. Anti‐HMGCR‐positive patients had only partial responses to multiple immunosuppressive medications, and their disease often took a chronic course. The DRB1*07:01 allele was present in all 5 patients, compared to 26.25% of healthy controls (corrected P= 0.01); none of the 5 juvenile patients had DRB1*11:01. Compared to children with other MSAs, muscle disease appears to be more severe in those with anti‐HMGCR autoantibodies. Like adults, children with anti‐HMGCR autoantibodies have severe weakness and high CK levels. In contrast to adults, in anti‐HMGCR‐positive children, there is a strong association with HLA–DRB1*07:01.

The article presents an interview with Joel Ostrov from Direct Travel. He discusses kind of challenges and opportunities in Direct Travel seeing as the industry recovers. He mentions what needs to happen for business travel to get back to where it was in 2019 for Direct Travel. He discusses virtual meetings had a major role to play in keeping people and businesses connected.

A never-before-seen letter penned by J.D. Salinger about his disinterest in Hollywood ('Salinger and Hollywood Were 'Rye' Correspondents') moved readers to share the 'Catcher in the Rye' authors apathy. I [...]

The article discusses a new federal legislation proposed by physician representatives that aims to permanently link Medicare physician payment updates to inflation. The legislation has garnered support from doctors' groups, including the American Medical Association, as it would help physician practices manage payment distributions and potentially improve access to care for Medicare patients.

A CCD Vlight curve for the eclipsing binary star AzV 73is presented. This new photometric observations are analysed together with previously published CCD Iphotometry from Udalski et al. ([CITE]) and spectrographic data from Niemela & Bassino ([CITE]), by means of the Wilson-Devinney code. It is found that this system is semi-detached, with an orbital inclination of roughly $86 \degr$and a separation of $42 R_{\odot}$. The sizes and masses are $R_1=11.53 \pm 0.5 R_{\odot}$, $M_1=25.26 \pm 0.7 M_{\odot}$, and $R_2=15.46 \pm 0.4 R_{\odot}$, $M_2=21.96 \pm 0.8 M_{\odot}$for the primary and secondary components, respectively.

We present a CCD Vlight curve of HV 2241, together with some observations in the Bband. We analysed our photometric data jointly with previously published radial velocities by means of the Wilson-Devinney code, and derived new values for the physical parameters of this massive eclipsing binary system. We confirm that this system is semi-detached, with the secondary (less massive and less luminous component) filling its Roche-lobe. From our analysis, we estimate the following masses and radii for the components of HV 2241: $M_1=36.2 \pm 0.7 {M}_{\odot}$, $R_1=14.9 \pm 0.4 {R}_{\odot}$, $M_2=18.4 \pm 0.7 {M}_{\odot}$and $R_2=13.7 \pm 0.4 {R}_{\odot}$. We review the spectral classification analysing HST and IUE data and discuss the temperature and the reddening for this star.

Henoch-Schönlein purpura (HSP), more recently termed immunoglobulin A (IgA) vasculitis, is a systemic small-vessel vasculitis characterized by perivascular IgA deposition. This disease manifests clinically as palpable purpura, arthralgia, gastrointestinal symptoms, and renal dysfunction. Although ileitis can be seen in HSP, terminal ileitis is virtually pathognomonic for Crohn disease. We present a comprehensive review of the literature on this association, including 2 cases of our own, to demonstrate the importance of considering HSP in the differential diagnosis of ileitis suggestive of Crohn disease. We review the growing body of literature suggesting a pathophysiologic link between the conditions, possibly through an IgA-mediated mechanism.

The article presents an interview with the author. Topics discusses include author views on the impact of Covid-19 pandemic's Delta variant on the travel programs in the Canada; mentions steps taken by his organization for the development of travel market in midst of pandemic; and also mentions challenges and opportunities faced by the organization in the pandemic.