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This paper examines the latest advancements in green growth among EU member countries, with a focus on Serbia. It aims to compare green growth indicators across different countries by employing two defined hypotheses. This analysis utilizes data from the OECD statistics database, specifically focusing on annual data related to CO2 emissions and renewable energy. The choice of these indicators is based on their causal relationship to green growth. The research is based on the methodology of comparative analysis for selected indicators. The first section applies to CO2 emission indicators with trends, while the second section analyses the renewable energy situation. All considerations were made by creating groups of EU member countries by year of accession: 2004 (for 10 countries), 2007 (for 2 countries), and 2013 (for Croatia) for selected indicators. The utilization of combined datasets facilitated the evaluation of positive trend outcomes in Serbia.

The subject of this paper is the examination of the impact of liquidity on the profitability of 100 companies in the processing sector of the Republic of Serbia with the highest level of business income in the period from 2016 to 2020. A regression with fixed effects was applied to the panel data. Based on the obtained results, it can be argued that there is no direct relationship between indicators of accelerated liquidity and net return on assets when it comes to the observed companies, which implies that the optimal amount of cash and cash equivalents that would enable the maximization of net return on assets cannot be determined either.. There is no direct connection between profitability and the length of the business cycle of the observed companies. On the other hand, a faster turnover of capital results in a higher level of profitability, as well as the growth of company assets, while higher indebtedness has negative implications for the profitability of companies in the processing sector. The obtained results have significant implications for the decisions of financial managers, for the financial sector, as well as for competent state institutions.

The aim of this study is to analyse the determinants of the growing agri-food export in the CEE countries. Using the SYS-GMM estimation, we control for the endogeneity problem. As the explanatory variables we use the variable that have been empirically proven as determinants of the agri-food export and available for observed countries. The obtained results show that the trade liberalisation increases the agri-food exports, while the EU enlargement indirectly affects the agri-food exports which is an important statement for policy-makers.

Background: Animal research demonstrates that pelvic sensory signalling at parturition initiates behavioural and emotional changes that are protective for mother and offspring. In contrast, research with humans has found no effect of caesarean delivery (i.e. procedure that blocks pelvic signalling) on mother's mental health. The lack of effect may reflect little consideration for the use of epidurals, another intervention that blocks pelvic signalling. The following study examines whether blocking pelvic signalling during delivery predicts postpartum depression symptomatology. Method: Longitudinal mental health data were collected prospectively from 142 primiparous women who had a caesarean delivery and/or received epidural anaesthesia (Intervention) or delivered vaginally without anaesthesia (No-Intervention). Measurements began in late pregnancy and continued through the first postpartum year. Results: Intervention mothers reported more depressive symptoms at the end of the first postpartum year compared to those in the No-Intervention group. This effect was independent of socio-cultural factors known to predict levels of depressive symptoms. Conclusion: These results suggest that pelvic sensory signalling may help to prepare women for the postpartum period. Considering there are many factors influencing the mental health of mothers, the present finding suggest that populations vulnerable to postpartum depression should consider a delivery without intervention, when medically permissible. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is the main arrhythmia associated with thromboembolic complications and cognitive impairment. In this study, we aimed to evaluate the relationship between cognitive impairment and different scoring systems developed for AF to improve the medical follow-up of cognitive impairment., Methods: Between January 2019 and December 2020, 124 patients between the age of 30 and 80 years, diagnosed with AF for at least 5 years and complaining about memory impairment during cardiological follow-up, were included in the study. The patients were divided into two groups based on their cognitive status as assessed by the Mini-Mental State Examination group 1 consisted of 52 patients with cognitive impairment and group 2 comprised 72 patients without cognitive impairment., Results: The ATRIA bleeding score had a positive moderate correlation ( r = 0.454, P < 0.001), the ATRIA stroke score had a strong correlation ( r = 0.738, P < 0.001), and the SAMe-TT 2 R 2 score had a strong correlation ( r = 0.688, P < 0.001) with cognitive impairment. However, CHADS 2 and CHA 2 DS 2 VASc scores were not statistically correlated with cognitive impairment. According to the receiver operating characteristic (ROC) curve, the area under the curve (AUC) of the ATRIA bleeding score was 0.761 with a 95% confidence interval (CI) of 0.678-0.844 and P < 0.001; also, for the ATRIA stroke score, AUC was 0.930 with a 95% CI of 0.886-0.974 and P < 0.001. In addition, for the SAMe-TT 2 R 2 score, AUC was 0.895 with a 95% CI of 0.838-0.952 and P < 0.001. In the pairwise comparison of AUC on ROC curves, the ATRIA stroke score and the SAMe-TT 2 R 2 score were statistically similar ( P = 0.324). ATRIA bleeding, ATRIA stroke, and SAMe-TT 2 R 2 scores were greater than CHADS 2 stroke score ( P : 0.0004, P < 0.0001, and P < 0.0001, respectively), but CHA 2 DS 2 -VASc and CHADS 2 stroke scores were statistically similar ( P : 0.402)., Conclusion: Both ATRIA stroke and SAMe-TT 2 R 2 scoring systems can provide a better correlation than CHADS 2 and CHA 2 DS 2 -VASc scores in patients with AF to evaluate their cognitive status. These two scores can be more useful to monitor the patients with AF for medical follow-up of cognitive status., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Annals of Indian Academy of Neurology.)

Glutamine is a conditionally essential nutrient for many cancer cells, but it remains unclear how consuming glutamine in excess of growth requirements confers greater fitness to glutamine-addicted cancers. By contrasting two breast cancer subtypes with distinct glutamine dependencies, we show that glutamine-indispensable triple-negative breast cancer (TNBC) cells rely on a non-canonical glutamine-to-glutamate overflow, with glutamine carbon routed once through the TCA cycle. Importantly, this single-pass glutaminolysis increases TCA cycle fluxes and replenishes TCA cycle intermediates in TNBC cells, a process that achieves net oxidation of glucose but not glutamine. The coupling of glucose and glutamine catabolism appears hard-wired via a distinct TNBC gene expression profile biased to strip and then sequester glutamine nitrogen, but hampers the ability of TNBC cells to oxidise glucose when glutamine is limiting. Our results provide a new understanding of how metabolically rigid TNBC cells are sensitive to glutamine deprivation and a way to select vulnerable TNBC subtypes that may be responsive to metabolic-targeted therapies., (© 2022. The Author(s).)

Benzodiazepines and antidepressants have been shown to change responses to unfairness; however, the effects of their combined use on unfairness evaluation are unknown. This study examines the effects of concomitant benzodiazepines and antidepressants long-term use on the evaluation of fair and unfair offers. To analyze behavioral changes on responses to unfairness, we compared the performance of medicated participants and healthy controls in the Ultimatum Game (UG), both in the proposer and in the respondent role. The results showed that long-term psychotropic users had the worse economic strategy by accepting less offers than control subjects. However, in the proposer role, the unfair offers made by participants were similar between groups. The present results suggest that long-term use of psychotropic medication, specifically the combination of benzodiazepines and antidepressants, may increase the sensitivity to unfairness, resulting in higher rejection rates in conditions where this strategy is the most disadvantageous., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fernandes, Garcez, Balaban, Barbosa, Pereira, Silveira, Marques-Teixeira and Gonçalves.)

Objective: While the effects of obesity on asthma are yet to be fully clarified, increased fat tissue is known to increase the severity of asthma and to impair asthma control. This study evaluated the effects of diet-induced weight loss on the characteristics of asthma in obese adults with asthma. Methods: A total of 55 obese individuals (BMI ≥ 30.0) with asthma were enrolled in the study and randomized into the diet or control groups. The anthropometric measurements, asthma control test (ACT) scores, asthma quality of life questionnaire (AQLQ) scores, pulmonary function tests (PFT) and daily food consumption of the participants were recorded and compared at the baseline and at study completion. Results: The changes recorded in body weight (diet -5.2 (4, 5); control, -0.1 (1.3)), ACT score (diet 2.0 (2.0); control 0.0 (1.7)) and AQLQ score (diet 0.8 ± 0.1; control -0.02 ± 0.5) of the participants in the diet group were significantly higher than in the control group ( p  = 0.00). The increases in forced expiratory volume in one second (FEV 1 ) and the forced vital capacity (FVC) measurements of the participants with weight loss of ≥5.0 percent were significant when compared to those with weight loss of <5.0 percent ( p  < 0.05). While total energy uptake and carbohydrate consumption at the end of study were found to be decreased in the diet group, they had increased in the control group ( p  < 0.05). Conclusion: Diet intervention improved asthma control and quality of life in obese patients with controlled asthma in this study. However to generalize this finding to all asthma patients, further studies including uncontrolled asthmatics are needed.

Face and body perception is mediated by configural mechanisms, which allow the perception of these stimuli as a whole, rather than the sum of individual parts. Indirect measures of configural processing in visual cognition are the face and body inversion effects (FIE and BIE), which refer to the drop in performance when these stimuli are perceived upside-down. Albeit FIE and BIE have been well characterized at the behavioral level, much still needs to be understood in terms of the neurophysiological correlates of these effects. Thus, in the current study, the brain's electrical activity has been recorded by a 128 channel electroencephalogram (EEG) in 24 healthy participants while perceiving (upright and inverted) faces, bodies and houses. EEG data were analyzed in both the time domain (i.e., event-related potentials-ERPs) and the frequency domain [i.e., induced theta (5-7 Hz) and gamma (28-45 Hz) oscillations]. ERPs amplitude results showed increased N170 amplitude for inverted faces and bodies (compared to the same stimuli presented in canonical position) but not for houses. ERPs latency results showed delayed N170 components for inverted (vs. upright) faces, houses, but not bodies. Spectral analysis of induced oscillations indicated physiological FIE and BIE; that is decreased gamma-band synchronization over right occipito-temporal electrodes for inverted (vs. upright) faces, and increased bilateral frontoparietal theta-band synchronization for inverted (vs. upright) faces. Furthermore, increased left occipito-temporal and right frontal theta-band synchronization for upright (vs. inverted) bodies was found. Our findings, thus, demonstrate clear differences in the neurophysiological correlates of face and body perception. The neurophysiological FIE suggests disruption of feature binding processes (decrease in occipital gamma oscillations for inverted faces), together with enhanced feature-based attention (increase in frontoparietal theta oscillations for inverted faces). In contrast, the BIE may suggest that structural encoding for bodies is mediated by the first stages of configural processing (decrease in occipital theta oscillations for inverted bodies)., (Copyright © 2020 Bossi, Premoli, Pizzamiglio, Balaban, Ricciardelli and Rivolta.)

Aptamer-based point-of-care (POC) diagnostics platforms may be of substantial benefit in forensic analysis as they provide rapid, sensitive, user-friendly, and selective analysis tools for detection. Aptasensors have not yet been adapted commercially. However, the significance of the applications of aptasensors in the literature exceeded their potential. Herein, in this review, a bottom-up approach is followed to describe the aptasensor development and application procedure, starting from the synthesis of the corresponding aptamer sequence for the selected analyte to creating a smart surface for the sensitive detection of the molecule of interest. Optical and electrochemical biosensing platforms, which are designed with aptamers as recognition molecules, detecting abused drugs are critically reviewed, and existing and possible applications of different designs are discussed. Several potential disciplines in which aptamer-based biosensing technology can be of greatest value, including forensic drug analysis and biological evidence, are then highlighted to encourage researchers to focus on developing aptasensors in these specific areas., Competing Interests: The authors declare no conflict of interest.

Background: Smoking is a key contributor to health and social inequalities and homeless smoking prevalence rates are 4 times higher than the general population. Research on homelessness and smoking to date has been concentrated predominantly in the US and Australia. This study aimed to describe smoking and quitting behaviour in homeless adult smokers in Great Britain. Data on perceptions of, and willingness to try, e-cigarettes were also gathered., Methods: Cross sectional survey of 283 adult smokers accessing homeless support services in Kent, the Midlands, London and Edinburgh. Participants answered a four-part survey: i) demographics; ii) current smoking behaviour and dependence (including the Fagerström Test of Cigarette Dependence [FTCD]); iii) previous quit attempts; and iv) e-cigarettes perceptions., Results: High levels of cigarette dependence were observed (FTCD: M = 7.78, sd ± 0.98). Although desire to quit was high, most had made fewer than 5 quit attempts and 90% of these lasted less than 24 h. 91.5% reported that others around them also smoked. Previous quit methods used included cold turkey (29.7%), NRT (24.7%), varenicline (22.3%) and bupropion (14.5%). 34% were willing or able to spend £20 or more for an e-cigarette and 82% had tried one in the past although 54% reported that they preferred smoking., Conclusion: We observed high nicotine dependence, few long-term quit attempts, strong desire to quit and amenability to both traditional cessation methods and e-cigarettes. Community embedded and non-routine approaches to cessation may be promising avenues promoting engagement with the homeless community. Likely barriers to uptake include low affordability, preference for cigarettes and high numbers of smoking acquaintances., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Prostate cancer cells exhibit altered cellular metabolism but, notably, not the hallmarks of Warburg metabolism. Prostate cancer cells exhibit increased de novo synthesis of fatty acids (FA); however, little is known about how extracellular FAs, such as those in the circulation, may support prostate cancer progression. Here, we show that increasing FA availability increased intracellular triacylglycerol content in cultured patient-derived tumor explants, LNCaP and C4-2B spheroids, a range of prostate cancer cells (LNCaP, C4-2B, 22Rv1, PC-3), and prostate epithelial cells (PNT1). Extracellular FAs are the major source (∼83%) of carbons to the total lipid pool in all cell lines, compared with glucose (∼13%) and glutamine (∼4%), and FA oxidation rates are greater in prostate cancer cells compared with PNT1 cells, which preferentially partitioned extracellular FAs into triacylglycerols. Because of the higher rates of FA oxidation in C4-2B cells, cells remained viable when challenged by the addition of palmitate to culture media and inhibition of mitochondrial FA oxidation sensitized C4-2B cells to palmitate-induced apoptosis. Whereas in PC-3 cells, palmitate induced apoptosis, which was prevented by pretreatment of PC-3 cells with FAs, and this protective effect required DGAT-1-mediated triacylglycerol synthesis. These outcomes highlight for the first-time heterogeneity of lipid metabolism in prostate cancer cells and the potential influence that obesity-associated dyslipidemia or host circulating has on prostate cancer progression. IMPLICATIONS: Extracellular-derived FAs are primary building blocks for complex lipids and heterogeneity in FA metabolism exists in prostate cancer that can influence tumor cell behavior., (©2019 American Association for Cancer Research.)

Breast cancer (BrCa) metabolism is geared toward biomass synthesis and maintenance of reductive capacity. Changes in glucose and glutamine metabolism in BrCa have been widely reported, yet the contribution of fatty acids (FAs) in BrCa biology remains to be determined. We recently reported that adipocyte coculture alters MCF-7 and MDA-MB-231 cell metabolism and promotes proliferation and migration. Since adipocytes are FA-rich, and these FAs are transferred to BrCa cells, we sought to elucidate the FA metabolism of BrCa cells and their response to FA-rich environments. MCF-7 and MDA-MB-231 cells incubated in serum-containing media supplemented with FAs accumulate extracellular FAs as intracellular triacylglycerols (TAG) in a dose-dependent manner, with MDA-MB-231 cells accumulating more TAG. The differences in TAG levels were a consequence of distinct differences in intracellular partitioning of FAs, and not due to differences in the rate of FA uptake. Specifically, MCF-7 cells preferentially partition FAs into mitochondrial oxidation, whereas MDA-MB-231 cells partition FAs into TAG synthesis. These differences in intracellular FA handling underpin differences in the sensitivity to palmitate-induced lipotoxicity, with MDA-MB-231 cells being highly sensitive, whereas MCF-7 cells are partially protected. The attenuation of palmitate-induced lipotoxicity in MCF-7 cells was reversed by inhibition of FA oxidation. Pretreatment of MDA-MB-231 cells with FAs increased TAG synthesis and reduced palmitate-induced apoptosis. Our results provide novel insight into the potential influences of obesity on BrCa biology, highlighting distinct differences in FA metabolism in MCF-7 and MDA-MB-231 cells and how lipid-rich environments modulate these effects., (© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Background: Recovery from obstetrics and gynecology (OB/GYN) surgery, including hysterectomy and cesarean section delivery, aims to restore function while minimizing hospital length of stay (LOS) and medical expenditures., Objective: Our analyses compare OB/GYN surgery patients who received combination intravenous (IV) acetaminophen and IV opioid analgesia with those who received IV opioid-only analgesia and estimate differences in LOS, hospitalization costs, and opioid consumption., Methods: We performed a retrospective analysis of the Premier Database between January 2009 and June 2015, comparing OB/GYN surgery patients who received postoperative pain management with combination IV acetaminophen and IV opioids with those who received only IV opioids starting on the day of surgery and continuing up to the second postoperative day. We performed instrumental variable 2-stage least-squares regressions controlling for patient and hospital covariates to compare the LOS, hospitalization costs, and daily opioid doses (morphine equivalent dose) of IV acetaminophen recipients with that of opioid-only analgesia patients., Results: We identified 225 142 OB/GYN surgery patients who were eligible for our study of whom 89 568 (40%) had been managed with IV acetaminophen and opioids. Participants averaged 36 years of age and were predominantly non-Hispanic Caucasians (60%). Multivariable regression models estimated statistically significant differences in hospitalization cost and opioid use with IV acetaminophen associated with $484.4 lower total hospitalization costs (95% CI = -$760.4 to -$208.4; P = 0.0006) and 8.2 mg lower daily opioid use (95% CI = -10.0 to -6.4), whereas the difference in LOS was not significant, at -0.09 days (95% CI = -0.19 to 0.01; P = 0.07)., Conclusion: Compared with IV opioid-only analgesia, managing post-OB/GYN surgery pain with the addition of IV acetaminophen is associated with decreased hospitalization costs and reduced opioid use.

The tumor stroma is a heterogeneous ecosystem comprising matrix, fibroblasts, and immune cells and has an important role in cancer progression. Adipocytes constitute a major component of breast stroma, and significant emerging evidence demonstrates a reciprocal metabolic adaptation between stromal adipocytes and breast cancer (BC) cells. Recent observations promote a model where adipocytes respond to cancer cell-derived endocrine and paracrine signaling to provide metabolic substrates, which in turn drive enhanced cancer cell proliferation, invasion, and treatment resistance. Further defining the mechanisms that underpin this dynamic interaction between stromal adipocytes and BC cells, especially in the context of obesity, may identify novel therapeutic strategies. These will become increasingly important in addressing the clinical challenges presented by obesity and metabolic syndromes., (Copyright © 2017. Published by Elsevier Ltd.)

Background: Pancreatic cancer has a five-year survival rate of ~8%, with characteristic molecular heterogeneity and restricted treatment options. Targeting metabolism has emerged as a potentially effective therapeutic strategy for cancers such as pancreatic cancer, which are driven by genetic alterations that are not tractable drug targets. Although somatic mitochondrial genome (mtDNA) mutations have been observed in various tumors types, understanding of metabolic genotype-phenotype relationships is limited., Methods: We deployed an integrated approach combining genomics, metabolomics, and phenotypic analysis on a unique cohort of patient-derived pancreatic cancer cell lines (PDCLs). Genome analysis was performed via targeted sequencing of the mitochondrial genome (mtDNA) and nuclear genes encoding mitochondrial components and metabolic genes. Phenotypic characterization of PDCLs included measurement of cellular oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using a Seahorse XF extracellular flux analyser, targeted metabolomics and pathway profiling, and radiolabelled glutamine tracing., Results: We identified 24 somatic mutations in the mtDNA of 12 patient-derived pancreatic cancer cell lines (PDCLs). A further 18 mutations were identified in a targeted study of ~1000 nuclear genes important for mitochondrial function and metabolism. Comparison with reference datasets indicated a strong selection bias for non-synonymous mutants with predicted functional effects. Phenotypic analysis showed metabolic changes consistent with mitochondrial dysfunction, including reduced oxygen consumption and increased glycolysis. Metabolomics and radiolabeled substrate tracing indicated the initiation of reductive glutamine metabolism and lipid synthesis in tumours., Conclusions: The heterogeneous genomic landscape of pancreatic tumours may converge on a common metabolic phenotype, with individual tumours adapting to increased anabolic demands via different genetic mechanisms. Targeting resulting metabolic phenotypes may be a productive therapeutic strategy.

Background: Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to support breast cancer progression is poorly understood., Results: Here, we show that co-culture of breast cancer cells with adipocytes revealed cancer cell-stimulated depletion of adipocyte triacylglycerol. Adipocyte-derived free fatty acids were transferred to breast cancer cells, driving fatty acid metabolism via increased CPT1A and electron transport chain complex protein levels, resulting in increased proliferation and migration. Notably, fatty acid transfer to breast cancer cells was enhanced from "obese" adipocytes, concomitant with increased stimulation of cancer cell proliferation and migration. This adipocyte-stimulated breast cancer cell proliferation was dependent on lipolytic processes since HSL/ATGL knockdown attenuated cancer cell responses., Conclusions: These findings highlight a novel and potentially important role for adipocyte lipolysis in the provision of metabolic substrates to breast cancer cells, thereby supporting cancer progression.

Objective: Many studies reported an improved prognosis in patients with Burkitt's lymphoma obviating the need of stem cell transplantation. However, prognosis of the advanced disease [i.e. Burkitt's cell leukemia (BCL)] has not been reported with current treatment modalities except for a few prospective trials. The aim of this study is to compare the prognoses of BCL patients with similarly treated and nontransplanted patients with other types of acute lymphoblastic leukemia (ALL) and with ALL patients that underwent allogeneic stem cell transplantation (ASCT) in their first remissions., Materials and Methods: In this retrospective analysis, BCL patients aged between 16 and 63 who were admitted between 2000 and 2014 to the hospitals of Hacettepe or Gazi University and were treated with intensive therapies aimed at cure were included. All ALL patients who were treated with a similar protocol not including transplantation during the same period (NT-ALL group) and all ALL patients who underwent ASCT in the first complete remission during the same period (T-ALL group) served as control groups., Results: The central nervous system or extramedullary involvement rates, lactate dehydrogenase levels, and white blood cell counts at diagnosis were higher in the BCL group than the NT-ALL group and these differences were significant. BCL patients had disease-free survival (DFS) durations comparable with the T-ALL cohort but NT-ALL patients had significantly shorter DFS durations. Both cumulative relapse incidence and cumulative nonrelapse mortality were higher in NT-ALL patients compared to the T-ALL group and BCL patients., Conclusion: DFS in BCL patients treated with a widely accepted modern regimen, R-HyperCVAD, is comparable to results in other ALL patients receiving allogeneic transplantation. Our results are in agreement with a few prospective noncomparative studies suggesting no further need for stem cell transplantation in BCL., Competing Interests: The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/or affiliations relevant to the subject matter or materials included.

Introduction: Recovery from orthopedic surgery is oriented towards restoring functional health outcomes while reducing hospital length of stay (LOS) and medical expenditures. Optimal pain management is a key to reaching these objectives. We sought to compare orthopedic surgery patients who received combination intravenous (IV) acetaminophen and IV opioid analgesia to those who received IV opioids alone and compared the two groups on LOS and hospitalization costs., Methods: We performed a retrospective analysis of the Premier Database (Premier, Inc.; between January 2009 and June 2015) comparing orthopedic surgery patients who received post-operative pain management with combination IV acetaminophen and IV opioids to those who received only IV opioids starting on the day of surgery and continuing up to the second post-operative day. The quarterly rate of IV acetaminophen use for all hospitalizations by hospital served as the instrumental variable in two-stage least squares regressions controlling for patient and hospital covariates to compare the LOS and hospitalization costs of IV acetaminophen recipients to opioid monotherapy patients., Results: We identified 4,85,895 orthopedic surgery patients with 1,74,805 (36%) who had received IV acetaminophen. Study subjects averaged 64 years of age and were predominantly non-Hispanic Caucasians (78%) and female (58%). The mean unadjusted LOS for IV acetaminophen patients was 3.2 days [standard deviation (SD) 2.6] compared to 3.9 days (SD 3.9) with only IV opioids (P < 0.0001). Average unadjusted hospitalization costs were $19,024.9 (SD $13,113.7) for IV acetaminophen patients and $19,927.6 (SD $19,578.8) for IV opioid patients (P < 0.0001). These differences remained statistically significant in our instrumental variable models, with IV acetaminophen associated with 0.51 days shorter hospitalization [95% confidence interval (CI) -0.58 to -0.44, P < 0.0001] and $634.8 lower hospitalization costs (95% CI -$1032.5 to -$237.1, P = 0.0018)., Conclusion: Compared to opioids alone, managing post-orthopedic surgery pain with the addition of IV acetaminophen is associated with shorter LOS and decreased hospitalization costs., Funding: Mallinckrodt Pharmaceuticals.

Clinical theories posit interpersonal stress as an important factor in the emergence and exacerbation of depression and anxiety, while neuroendocrine research confirms the association of these syndromes with dysregulation in a major stress response system, the hypothalamic-pituitary-adrenal (HPA) axis. However, the proposal that depression and anxiety symptoms and diagnoses are associated with problematic HPA responses to close relationship stress has not been directly tested. We examined 196 heterosexual dating couples' depression and anxiety symptoms and diagnoses, assessed with questionnaires and diagnostic interviews, in relation to cortisol responses to discussion of an unresolved relationship conflict. Participants provided seven salivary samples in anticipation of and directly following the discussion, and throughout an hour-long recovery period, which were assayed for cortisol. Multilevel models of the HPA response predicted by symptoms or diagnoses showed that women's depressive symptoms predicted attenuated cortisol levels, with a flatter response curve. In contrast, men's depression symptoms and women's anxiety symptoms and diagnoses predicted higher cortisol levels. These findings highlight the importance of examining sex differences in responses to interpersonal stressors for understanding HPA dysregulation in internalizing psychopathology., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Osteomyelitis (OM), is a rare disease in developed countries. It is defined as a progressive inflammation of the bone and the bone marrow, and characterized by formation of necrotic bone. This disease is more common in the lower jaw, which resembles the structure of a long bone. However, there are histologic and microbiologic characteristics that constitute important factors in the etiology and pathogenesis of the disease and therefore it is not possible to make an analogy from OM of long bones to OM of the jaws. The diagnosis of OM is based on a detailed anamnesis, clinical findings, laboratory tests and imaging. The treatment of OM consists of surgical treatment, which is considered the mainstay of the treatment, and antibiotic treatment, parenteral and oral which is considered as complementary therapy. There are several surgical procedures, according to the extent of the lesion, which include: drainage, curettage, sequestrectomy, saucerization, decortications and resection. A case of osteomyelitis of the lower jaw after dental treatment is presented. The patient underwent segmental resection and reconstruction.

There are numerous surgical approaches for oro-antral-fistula (OAF) closure. Secondary sinus disease is still considered by many experts a relative contra indication for primary closure. To describe a single-stage combined endoscopic sinus surgery and per-oral buccal fat pad (BFP) flap approach for large OAF causing chronic maxillary sinusitis. The records of all the patients with OAF and chronic manifestations of secondary rhinosinusitis that were treated between 2010 and 2013 in our tertiary care medical center were reviewed. The exclusion criteria were: OAF ≤ 5 mm, resolved sino-nasal disease, OAF secondary to malignancy, recurrent fistula, medical history that included radiotherapy to the maxillary bone and age <18 years. Each procedure was performed by a team consisting of a rhinologist and a maxillofacial surgeon. The surgical approach included an endoscopic middle antrostomy with maxillary sinus drainage, and a per-oral BFP regional flap for OAF closure. Total OAF closure, complications and need for revision surgeries. Forty-five patients that underwent OAF closure together with sinus surgery using a combined endoscopic sinus surgery (ESS) and BFP flap approach met the inclusion criteria. There were 28 males and 17 females with a mean ± SD age of 53.5 ± 14.9 years (range 22-80 years). The presenting signs and symptoms included purulent rhinorrhea (n = 22, 48.9 %), foreign body in sinus (n = 10, 22.2 %) nasal congestion (n = 7, 15.5 %), halitosis (n = 6, 13.3 %) and pain (n = 5, 12.2 %). Surgical complications included local pain (n = 2, 4.4 %), persistent rhinitis (n = 2, 4.4 %) and synechia (n = 1, 2.2 %). One patient required revision surgery due to an unresolved OAF. The OAF of all the other 44 patients (97.8 %) was closed after the first procedure and the paranasal sinuses on the treated side were completely recovered. The mean follow-up time for the group was 7.6 ± 4.3 months (7-21 months), and no untoward sequelae or recurrence were reported. Combined, one step, endoscopic Maxillary sinus drainage together with per-oral BFP flap approach is an efficacious surgical approach for safe closure of OAFs that are complicated with secondary chronic maxillary sinusitis.

The three peroxisome proliferator-activated receptor (PPAR) isoforms; PPARα, PPARγ and PPARδ, play central roles in lipid metabolism and glucose homeostasis. Dual PPARα/γ agonists, which stimulate both PPARα and PPARγ isoforms to similar extents, are gaining popularity as it is believed that they are able to ameliorate the unwanted side effects of selective PPARα and PPARγ agonists; and may also be used to treat dyslipidemia and type 2 diabetes mellitus simultaneously. In this study, virtual screening of natural product libraries, using both structure-based and ligand-based drug discovery approaches, identified ten potential dual PPARα/γ agonist lead compounds (9-13 and 16-20). In vitro assays confirmed these compounds to show no statistically significant toxicity to cells, with the exception of compound 12 which inhibited cell growth to 74.5%±3.5 and 54.1%±3.7 at 50μM and 100μM, respectively. In support of their potential as dual PPARα/γ agonists, all ten compounds upregulated the expression of cholesterol transporters ABCA1 and ABCG1 in THP-1 macrophages, with indoline derivative 16 producing the greatest elevation (2.3-fold; 3.3-fold, respectively). Furthermore, comparable to the activity of established PPARα and PPARγ agonists, compound 16 stimulated triacylglycerol accumulation during 3T3-L1 adipocyte differentiation as well as fatty acid β-oxidation in HuH7 hepatocytes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: To report our experience with combined one-stage double-team maxillary sinus floor elevation (SFE) and endonasal endoscopic sinus surgery (ESS) procedure for concomitant inflammatory sinonasal pathologies., Material and Methods: Clinical records of all patients that underwent maxillary SFE in conjunction with endonasal ESS for the treatment of inflammatory sinonasal pathologies between 2011 and 2013 were retrospectively reviewed. All included patients had a sinonasal-related pathology that was first suggested by the referring physician and was later confirmed clinically and radiographically by our combined team comprised of otorhinolaryngologist and maxillofacial surgeons., Results: Fifteen combined SFE+ESS surgeries were performed using either xenograft-allograft mixture or autograft-xenograft-allograft mixture. The study group included seven males and eight females, whose median age was 55 years (range, 45-78 years). Seven patients underwent a unilateral SFE, and eight patients underwent bilateral SFEs. During the same session, four patients also underwent septoplasty for deviated nasal septum, five patients underwent bilateral maxillary antrostomy, 10 patients underwent unilateral maxillary antrostomy, and six patients underwent maxillary sinus cyst resection. Seven combined procedures were performed under active infection. There were no intra-operative complications, and all SFE+ESS combined procedures were successful. Three patients required extended postoperative antibiotic treatment for persistent sinusitis. One patient reported infraorbital hypoesthesia., Conclusions: We first report the promising outcomes of the double-team one-stage SFE+ESS procedure performed by a combined team of otorhinolaryngologist and maxillofacial surgeons, including on patients presenting with an infection of the sinuses at the time of surgery., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

There are numerous surgical approaches for oro-antral-fistula (OAF) closure. Secondary sinus disease is still considered by many experts a relative contra indication for primary closure. To describe a single-stage combined endoscopic sinus surgery and per-oral buccal fat pad (BFP) flap approach for large OAF causing chronic maxillary sinusitis. The records of all the patients with OAF and chronic manifestations of secondary rhinosinusitis that were treated between 2010 and 2013 in our tertiary care medical center were reviewed. The exclusion criteria were: OAF 5 mm, resolved sino-nasal disease, OAF secondary to malignancy, recurrent fistula, medical history that included radiotherapy to the maxillary bone and age <18 years. Each procedure was performed by a team consisting of a rhinologist and a maxillofacial surgeon. The surgical approach included an endoscopic middle antrostomy with maxillary sinus drainage, and a per-oral BFP regional flap for OAF closure. Total OAF closure, complications and need for revision surgeries. Forty-five patients that underwent OAF closure together with sinus surgery using a combined endoscopic sinus surgery (ESS) and BFP flap approach met the inclusion criteria. There were 28 males and 17 females with a mean ± SD age of 53.5 ± 14.9 years (range 22-80 years). The presenting signs and symptoms included purulent rhinorrhea (n = 22, 48.9%), foreign body in sinus (n = 10, 22.2%) nasal congestion (n = 7, 15.5%), halitosis (n = 6, 13.3%) and pain (n = 5, 12.2%). Surgical complications included local pain (n = 2, 4.4%), persistent rhinitis (n = 2, 4.4%) and synechia (n = 1, 2.2%). One patient required revision surgery due, to an unresolved OAF. The OAF of all the other 44 patients (97.8%) was closed after the first procedure and the paranasal sinuses on the treated side were completely recovered. The mean follow-up time for the group was 7.6 ± 4.3 months (7-21 months), and no untoward sequelae or recurrence were reported. Combined, one step, endoscopic Maxillary sinus drainage together with per-oral BFP flap approach is an efficacious surgical approach for safe closure of OAFs that are complicated with secondary chronic maxillary sinusitis.

Glutamine is conditionally essential in cancer cells, being utilized as a carbon and nitrogen source for macromolecule production, as well as for anaplerotic reactions fuelling the tricarboxylic acid (TCA) cycle. In this study, we demonstrated that the glutamine transporter ASCT2 (SLC1A5) is highly expressed in prostate cancer patient samples. Using LNCaP and PC-3 prostate cancer cell lines, we showed that chemical or shRNA-mediated inhibition of ASCT2 function in vitro decreases glutamine uptake, cell cycle progression through E2F transcription factors, mTORC1 pathway activation and cell growth. Chemical inhibition also reduces basal oxygen consumption and fatty acid synthesis, showing that downstream metabolic function is reliant on ASCT2-mediated glutamine uptake. Furthermore, shRNA knockdown of ASCT2 in PC-3 cell xenografts significantly inhibits tumour growth and metastasis in vivo, associated with the down-regulation of E2F cell cycle pathway proteins. In conclusion, ASCT2-mediated glutamine uptake is essential for multiple pathways regulating the cell cycle and cell growth, and is therefore a putative therapeutic target in prostate cancer., (© 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.)

Currently, there is renewed interest in elucidating the metabolic characteristics of cancer and how these characteristics may be exploited as therapeutic targets. Much attention has centered on glucose, glutamine and de novo lipogenesis, yet the metabolism of fatty acids that arise from extracellular, as well as intracellular, stores as triacylglycerol has received much less attention. This review focuses on the key pathways of fatty acid metabolism, including uptake, esterification, lipolysis, and mitochondrial oxidation, and how the regulators of these pathways are altered in cancer. Additionally, we discuss the potential link that fatty acid metabolism may serve between obesity and changes in cancer progression.

Vitamin D status, measured as serum 25-hydroxyvitamin D (25OHD) concentration, is determined by rates of input and of degradation. The half-life of 25OHD is surprisingly long for a steroid and much longer than its blood transporter, vitamin D binding protein. There is some evidence to suggest that vitamin D itself is stored in fat, whereas 25OHD concentrations are usually related to muscle-related parameters such as lean body mass and exercise. Both muscle and fat cells come from the mesenchymal cell lineage. We recently published evidence for net uptake of 25OHD into differentiated muscle cells, in a process that was megalin dependent, and speculated that this uptake might contribute to the extended half-life of 25OHD. Whether 25OHD is also taken up into cells of the adipocyte lineage is not clear. In the current study, we used the C2 muscle cell line as a source of myoblasts that were differentiated in culture to myotubes and 3T3-L1 pre-adipocytes that were differentiated into adipocytes in culture. We incubated the cells with trititated 25OHD and measured net uptake 4 and 16h afterwards. Differentiated myotubes took up labeled 25OHD in a time-dependent process to a far greater extent than myoblasts. In contrast, pre-adipocytes, but not differentiated adipocytes, accumulated labeled 25OHD in a time-dependent manner, though to a lesser extent than myotubes. Myotubes, but not myoblasts, showed megalin expression by immunohistochemistry. Pre-adipocytes, but not adipocytes, also showed expression of megalin. Since skeletal muscle consists mainly of differentiated muscle cells, while adipose tissue is mainly differentiated fat cells, it seems likely that muscle, but not fat tissue, provides a large extravascular pool through which 25OHD circulates and that this protects 25OHD from degradation. This article is part of a Special Issue entitled '16th Vitamin D Workshop'., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The way romantic partners behave during conflict is known to relate to stress responses, including activation of the hypothalamic-pituitary-adrenal (HPA) axis; however, little attention has been paid to interactive effects of partners' behaviors, or to behavior outside of marital relationships. This study examined relations between unmarried partners' negative and positive behaviors during discussion of conflict and their HPA responses, including both main effects and cross-partner interactions. Emerging adult opposite-sex couples (n=199) participated in a 15-minute conflict discussion and afterward rated their behavior on 3 dimensions: conflictual, holding back, and supportive. Seven saliva samples collected before and after the discussion were assayed for cortisol to determine HPA response. Quadratic growth models demonstrated associations between male×female partners' behaviors and cortisol trajectories. Two negative dyadic patterns-mutual conflictual behavior (negative reciprocity); female conflictual/male holding back (demand-withdraw)-and one positive pattern-mutual supportive behavior-were identified. Whereas negative patterns related to lower cortisol and impaired post-discussion recovery for women, the positive pattern related to lower cortisol and better recovery for men. Women's conflictual behavior only predicted problematic cortisol responses if their partner was highly conflictual or holding back; at lower levels of these partner behaviors, the opposite was true. This work demonstrates similar costs of negative reciprocity and demand-withdraw and benefits of supportive conflict dynamics in dating couples as found in marital research, but associations with HPA are gender-specific. Cross-partner interactions suggest that behavior during discussion of conflict should not be categorized as helpful or harmful without considering the other partner's behavior., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Granulocytic sarcoma is a rare tumor composed of immature granulocytic cells that is usually associated with acute myelogenous leukemia. Intraparenchymal cranial localization without skull, meningeal, or bone marrow invasion is extremely rare. The mechanisms of intraparenchymal cranial localization of GS remains unknown, as only 10 cases with cerebellar granulocytic sarcoma have been previously reported. Herein, we report a four year old boy with cerebellar localization of granulocytic sarcoma.

This article examined the relation of five subtypes of trauma symptoms to hypothalamus-pituitary-adrenal (HPA) functioning as assessed with salivary cortisol before, during, and after an experimentally induced interpersonal conflict task in 194 heterosexual young adult couples. Trauma history and symptoms were assessed through structured clinical interviews and standardized self-report measures. Hierarchical linear modeling was used to analyze the effects of trauma symptoms on trajectories of cortisol reactivity to and recovery from the interpersonal stress. Trauma-related anxiety, depression, sleep disturbances, and dissociation significantly predicted cortisol reactivity and recovery. Trauma-related anxiety, sleep disturbances, and sexual problems significantly predicted partners' cortisol reactivity to interpersonal stress.

Although regarded as a benign condition, simple hypertrichosis may be very disturbing to a child cosmetically. An abnormality in androgen metabolism has been implied in the etiology of simple hypertrichosis recently. This study was undertaken to investigate the effect of spironolactone therapy for its antiandrogenic property in 12 prepubertal girls with hypertrichosis with no underlying etiology. The girls, with a mean age of 6.9 (1.2) years, had normal height and bone age. Basal hormone levels and adrenocorticotropin stimulation test results were in the normal ranges. Pelvic and adrenal ultrasound did not reveal pathology. Total and medullary hair width were measured from hair taken from preauricular, anterior midthigh, distal and proximal forearm areas. Spironolactone was started at an oral dose of 25 and increased to 100 mg x m(-2) x day(-1) twice daily for 1 year. Total hair width decreased significantly in the preauricular and anterior midthigh regions up to 6-9 months of treatment. Medullary hair width, which was affected by therapy to a greater extent, decreased significantly in all regions up to 6 months. Both total and medullary hair width showed a tendency to increase afterwards. No side effects were encountered. Spironolactone may be used in the treatment of simple hypertrichosis; however, more data are needed to clarify the efficacy and safety of anti-androgen therapy in hypertrichosis.

We have produced, by using a sonicate of Borrelia burgdorferi, a monoclonal antibody (MAb), NYSP39H, that is specific for the P39 protein band. This MAb reacted with 13 isolates of B. burgdorferi but not with eight different spirochetes (four borrelias, two leptospiras, and two treponemas). Surface labeling of B. burgdorferi with biotin and subsequent treatment with Nonidet P-40 showed that P39 was not biotinylated but was extracted with Nonidet P-40, indicating that it is present within the outer membrane, but not on the surface of the spirochete. Immunoelectron microscopy revealed the immunogold probe primarily at the cytoplasmic membrane region of the spirochete. The MAb detected B. burgdorferi in the indirect fluorescent-antibody test only when the spirochetes from a culture or in a tick homogenate were fixed with polylysine and not with acetone. NYSP39H appears to be an appropriate probe for use in the specific detection of B. burgdorferi.

Background: F1 hybrids of New Zealand Black (NZB) and New Zealand White (NZW) mice develop autoimmune glomerulonephritis resembling human lupus nephritis. Susceptibility to this complex autoimmune syndrome in humans and mice has been linked to genes mapping in or near the major histocompatibility complex that govern immune responses and levels of certain complement components. Previous studies showed that both parental strains contribute major histocompatibility complex-linked genes that are important for disease of the F1 hybrid., Experimental Design: New inbred strains of New Zealand Mixed (NZM) mice were derived by selective inbreeding of progeny of a cross between NZB and NZW mice. Twelve of the 27 new NZM strains were selected for analysis. Mice were observed for up to 10 months of age to document the occurrence of nephritis and strain-specific differences in disease expression. H-2, Hc, and coat color loci were determined for each strain to establish homozygosity of NZB and NZW polymorphic markers. Strains were screened for the presence of anti-dsDNA autoantibodies., Results: In some NZM strains early onset of lupus nephritis in females resembled the (NZB x NZW)F1 model, whereas in other strains early disease also occurred in males. Age at death and severity of nephritis vary among the lines; a few strains remain relatively free of glomerular lesions. Histocompatibility (H-2) typing showed that all strains are homozygous for the NZW haplotype (Ku, Au, Sz, Dz). Coat color analysis for four loci on chromosomes 2, 4, and 7 was consistent with specific reassortments and recombinations to explain the grey, tan, and white mice with red/pink eyes and the presence or absence of the fifth component of serum complement (C5) (Hc, chromosome 2). Anti-dsDNA autoantibodies were found in all but one of the NZM strains reported here., Conclusions: The NZM strains of mice are a unique set of inbred strains that have inherited various genomic segments of the two parental strains that lead to phenotypic differences in disease expression. These results indicate that the previously proposed strict requirement for H-2 heterozygosity for the development of nephritis in the (NZB x NZW)F1 hybrid mice may not be valid. It is assumed that both the Lpn-1 locus of NZB and the Lpn-2 locus of NZW and a sufficient number of other disease-associated genes of both ancestral strains have been recombined in these new strains to produce the various patterns of renal disease.