Percutaneous Heel Cord Release for Clubfoot: A Retrospective, Multicentre Cost Analysis

Purpose The Ponseti method of treatment is the standard of care for idiopathic clubfoot. Following serial casting, percutaneous tendo-Achilles tenotomy (TAT) is performed to correct residual equinus. This procedure can be performed in either the outpatient clinic or the operating room. The purpose of this study was to evaluate the expense of this procedure by examining hospital charges in both settings. Methods We retrospectively reviewed charts of 382 idiopathic clubfoot patients with a mean age of 2.4 months (0.6 to 26.6) treated with the Ponseti method at three institutions. Patients were divided into three groups depending on the setting for the TAT procedure: 140 patients in the outpatient clinic (CL), 219 in the operating room with discharge following the procedure (OR) and 23 in the operating room with admission to hospital for observation (OR+). Medical records were reviewed to analyze age, deformity, perioperative complications and specific time spent in each setting. Hospital charges for all three groups were standardized to one institution\u27s charge structure. Results Charges among the three groups undergoing TAT (CL, OR, OR+) were found to be significantly different ($3840.60 versus$7962.30 versus $9110.00, respectively; p ≤ 0.001), and remained significant when separating unilateral and bilateral deformities (p \u3c 0.001). There were nine total perioperative complications (six returns to the ER and three unexpected admissions to the hospital): five (2.3%) in the OR group, four (17.4%) in the OR+ group and none in the CL group. The OR+ group statistically had a higher rate of complications compared with the other two groups (p = 0.006). The total event time of the CL group was significantly shorter compared with the OR and OR+ groups (129.1, 171.7 and 1571.6 minutes respectively; p \u3c 0.001). Conclusion Hospital charges and total event time were significantly less when percutaneous TAT was performed in the outpatient clinic compared with the operating room. In addition, performing the procedure in clinic was associated with the lowest rate of complications. Level of Evidence Therapeutic, Level II

Dietary Methionine Restriction Regulates Liver Protein Synthesis and Gene Expression Independently of Eukaryotic Initiation Factor 2 Phosphorylation in Mice

Background: The phosphorylation of eukaryotic initiation factor 2 (p-eIF2) during dietary amino acid insufficiency reduces protein synthesis and alters gene expression via the integrated stress response (ISR).Objective: We explored whether a Met-restricted (MR) diet activates the ISR to reduce body fat and regulate protein balance.Methods: Male and female mice aged 3-6 mo with either whole-body deletion of general control nonderepressible 2 (Gcn2) or liver-specific deletion of protein kinase R-like endoplasmic reticulum kinase (Perk) alongside wild-type or floxed control mice were fed an obesogenic diet sufficient in Met (0.86%) or an MR (0.12% Met) diet for ≤5 wk. Ala enrichment with deuterium was measured to calculate protein synthesis rates. The guanine nucleotide exchange factor activity of eIF2B was measured alongside p-eIF2 and hepatic mRNA expression levels at 2 d and 5 wk. Metabolic phenotyping was conducted at 4 wk, and body composition was measured throughout. Results were evaluated with the use of ANOVA (P < 0.05).Results: Feeding an MR diet for 2 d did not increase hepatic p-eIF2 or reduce eIF2B activity in wild-type or Gcn2-/- mice, yet many genes transcriptionally regulated by the ISR were altered in both strains in the same direction and amplitude. Feeding an MR diet for 5 wk increased p-eIF2 and reduced eIF2B activity in wild-type but not Gcn2-/- mice, yet ISR-regulated genes altered in both strains similarly. Furthermore, the MR diet reduced mixed and cytosolic but not mitochondrial protein synthesis in both the liver and skeletal muscle regardless of Gcn2 status. Despite the similarities between strains, the MR diet did not increase energy expenditure or reduce body fat in Gcn2-/- mice. Finally, feeding the MR diet to mice with Perk deleted in the liver increased hepatic p-eIF2 and altered body composition similar to floxed controls.Conclusions: Hepatic activation of the ISR resulting from an MR diet does not require p-eIF2. Gcn2 status influences body fat loss but not protein balance when Met is restricted

Characterizing Bufferbloat and its Impact at End-hosts

Part 2: Performance at the EdgeInternational audienceWhile buffers on forwarding devices are required to handle bursty Internet traffic, overly large or badly sized buffers can interact with TCP in undesirable ways. This phenomenon is well understood and is often called “bufferbloat”. Although a number of previous studies have shown that buffering (particularly, in home) can delay packets by as much as a few seconds in the worst case, there is less empirical evidence of tangible impacts on end-users. In this paper, we develop a modified algorithm that can detect bufferbloat at individual end-hosts based on passive observations of traffic. We then apply this algorithm on packet traces collected at 55 end-hosts, and across different network environments. Our results show that 45 out of the 55 users we study experience bufferbloat at least once, 40% of these users experience bufferbloat more than once per hour. In 90% of cases, buffering more than doubles RTTs, but RTTs during bufferbloat are rarely over one second. We also show that web and interactive applications, which are particularly sensitive to delay, are the applications most often affected by bufferbloat

Leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes

The aim of the present study was to gain insight into the signaling pathway used by leptin to stimulate lipolysis. The lipolytic rate of white adipocytes from sex- and age-matched lean (+/+) and fa/fa rats was determined in the absence or presence of leptin together with a number of agents acting at different levels of the signaling cascade. Leptin did not modify FSK-, dbcAMP-, and IBMX-stimulated lipolysis. Lipolysis can also be maximally stimulated by lowering media adenosine levels with adenosine deaminase (ADA), i.e., in the ligand-free state. Although ADA produced near maximal lipolysis in adipocytes of lean animals, only half of the maximal lipolytic rate (50.9+/-3.2%) was achieved in fat cells from fa/fa rats (P=0.0034). In adipocytes from lean animals preincubated with ADA, leptin caused a concentration-related stimulation of lipolysis (P=0.0001). However, leptin had no effect on the lipolytic activity of adipocytes in the ligand-free state from fa/fa rats. The adenosine A1 receptor agonist CPA effectively inhibited basal lipolysis in both lean and obese adipocytes (P=0.0001 and P=0.0090, respectively). Leptin had no effect on the lipolytic rate of adipocytes isolated from fa/fa rats and preincubated with CPA. When adipocytes were incubated with the A1 receptor antagonist DPCPX, a significant increase in glycerol release was observed in fa/fa fat cells (P=0.009), whereas cells isolated from lean rats showed no differences to ADA-stimulated lipolysis. After pretreatment with PTX, which inactivates receptor-mediated Gi function, adipocytes of obese rats became as responsive to the stimulatory actions of ISO as cells from lean rats (P=0.0090 vs. ISO in fa/fa rats; P=0.2416 vs. lean rats, respectively). PTX treatment of lean cells, however, did not alter their response to this lipolytic agent. It can be concluded that the lipolytic effect of leptin is located at the adenylate cyclase/Gi proteins level and that leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes

Studies on the antiobesity effect of zinc-α2-glycoprotein in the ob/ob mouse

OBJECTIVE: To investigate the mechanism of the lipid depletion by zinc-a(2)-glycoprotein (ZAG). DESIGN: Studies were conducted in the ob/ob mouse, or on isolated adipocytes from these animals or their lean counterparts. RESULTS: Treatment of these animals for 15 days with ZAG (100? µg, intravenously, daily) resulted in a reduction of body weight of 6.55? g compared with phosphate-buffered saline-treated controls, without a change in food or water intake, but with a 0.4?°C rise in rectal temperature. ZAG-treated mice had a 30% reduction in carcass fat mass and a twofold increase in weight of brown adipose tissue. Epididymal adipocytes from ZAG-treated mice showed an increased expression of ZAG and hormone-sensitive lipase (HSL), and this was maintained for a further 3 days in the absence of ZAG. There was an increased lipolytic response to isoproterenol, which was retained for 3 days in vitro in the absence of ZAG. Expression of HSL was also increased in subcutaneous and visceral adipose tissue, as was also adipose triglyceride lipase (ATGL). There was a rapid loss of labelled lipid from epididymal adipose tissue of ZAG-treated mice, but not from the other depots, reflecting the difference in sensitivity to lipolytic stimuli. The increased expression of HSL and ATGL may involve the extracellular signal-regulated kinase (ERK) pathway, as the active (phospho) form was upregulated in all adipose depots after ZAG administration, whereas in vitro studies showed induction of HSL and ATGL by ZAG to be attenuated by PD98059, an inhibitor of the ERK pathway. CONCLUSION: These results suggest that ZAG not only induces direct lipolysis, but also sensitizes adipose tissue to other lipolytic stimuli

The quality of options in strategic decision making: a study about creativity and completeness in business decision making

A qualidade das decisões estratégicas dos empresários está diretamente relacionada à capacidade que eles demonstram para encontrar alternativas criativas quando enfrentam os problemas de suas empresas. Essas alternativas podem ser geradas intuitivamente, utilizando heurísticas. As pesquisas sobre geração de alternativas têm indicado consistentemente que as pessoas não são eficientes nessa atividade. As explicações para esse fato, contidas na literatura sobre decisão, não são conclusivas e permitem especulações a respeito. Para explorar essa questão e relacioná-la ao administrador brasileiro, foi idealizado um experimento com 174 alunos de quatro cursos de MBA para avaliar a originalidade e a completude das alternativas. O experimento e a respectiva análise basearam-se na confluência da pesquisa experimental, oriunda da psicologia cognitiva da decisão, com as visões da ciência da decisão organizacional tradicional e o novo campo de estudo das decisões intuitivas ou naturalísticas. Para mensurar a criatividade das alternativas apresentadas durante o experimento, empregou-se o conceito de árvore hierárquica, que demonstrou ser uma poderosa ferramenta para a tipologia de alternativas. O resultado desse experimento confirmou o baixo desempenho em geração de alternativas dos gerentes e, ao mesmo tempo, indicou que, provavelmente, a etapa de geração de alternativas isolada da etapa de escolha pode melhorar a qualidade das alternativas. A heurística, por sua vez, não demonstrou influenciar o conjunto de alternativas geradas. _________________________________________________________________________________________ ABSTRACT: The quality of strategic decisions of executives is directly related to the ability they have to find creative alternatives when facing business problems. These alternatives could be generated intuitively, using heuristics. On the other hand, the researches on alternatives generation have consistently indicated that people are not efficient on this duty. The argument for that, contained in the decision’s literature, is not conclusive and it allows speculation about it. To explore this issue and relate it to the Brazilian Administration, an experiment was designed for 174 students of four courses of MBA. The experiment and the analysis were resulted from the confluence between the experimental research from decision cognitive psychology with science’s vision of the traditional organizational decision and the new field of study on naturalistic or intuitive decisions. To measure the creativity of the alternatives presented during the experiment, the concept of hierarchical tree was utilized and it has proved a powerful tool to the typology of alternatives. The result of this experiment confirmed the poor performance in alternatives generation by managers and at the same time, indicated that probably, the generation of options isolated of analysis can produce better quality of alternatives. The heuristic, do not demonstrated any influence on options generated

Physiologic Responses to Dietary Sulfur Amino Acid Restriction in Mice Are Influenced by Atf4 Status and Biological Sex

Background: Dietary sulfur amino acid restriction (SAAR) improves body composition and metabolic health across several model organisms in part through induction of the integrated stress response (ISR). Objective: We investigate the hypothesis that activating transcription factor 4 (ATF4) acts as a converging point in the ISR during SAAR. Methods: Using liver-specific or global gene ablation strategies, in both female and male mice, we address the role of ATF4 during dietary SAAR. Results: We show that ATF4 is dispensable in the chronic induction of the hepatokine fibroblast growth factor 21 while being essential for the sustained production of endogenous hydrogen sulfide. We also affirm that biological sex, independent of ATF4 status, is a determinant of the response to dietary SAAR. Conclusions: Our results suggest that auxiliary components of the ISR, which are independent of ATF4, are critical for SAAR-mediated improvements in metabolic health in mice