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Background:. Nasal airway obstruction (NAO) due to nasal anatomic deformities is known to be more common among cleft patients than the general population, yet information is lacking regarding severity and variability of cleft-associated nasal obstruction relative to other conditions causing NAO. This preliminary study compares differences in NAO experienced by unilateral cleft lip nasal deformity (uCLND) subjects with noncleft subjects experiencing NAO. Methods:. Computational modeling techniques based on patient-specific computed tomography images were used to quantify the nasal airway anatomy and airflow dynamics in 21 subjects: 5 healthy normal subjects; 8 noncleft NAO subjects; and 8 uCLND subjects. Outcomes reported include Nasal Obstruction Symptom Evaluation (NOSE) scores, cross-sectional area, and nasal resistance. Results:. uCLND subjects had significantly larger cross-sectional area differences between the left and right nasal cavities at multiple cross sections compared with normal and NAO subjects. Median and interquartile range (IQR) NOSE scores between NAO and uCLND were 75 (IQR = 22.5) and 67.5 (IQR = 30), respectively. Airflow partition difference between both cavities were: median = 9.4%, IQR = 10.9% (normal); median = 31.9%, IQR = 25.0% (NAO); and median = 29.9%, IQR = 44.1% (uCLND). Median nasal resistance difference between left and right nasal cavities were 0.01 pa.s/ml (IQR = 0.03 pa.s/ml) for normal, 0.09 pa.s/ml (IQR = 0.16 pa.s/ml) for NAO and 0.08 pa.s/ml (IQR = 0.25 pa.s/ml) for uCLND subjects. Conclusions:. uCLND subjects demonstrated significant asymmetry between both sides of the nasal cavity. Furthermore, there exists substantial disproportionality in flow partition difference and resistance difference between cleft and noncleft sides among uCLND subjects, suggesting that both sides may be dysfunctional.

Background: Prolonged morphine treatment in infancy is associated with a high incidence of opioid tolerance and dependence, but our knowledge of the long-term consequences of this treatment is sparse. Using a rodent model, we examined the (1) short- and (2) long-term effects of prolonged morphine administration in infancy on body weight and brain volume, and (3) we evaluated if subsequent dosing in adulthood poses an increased brain vulnerability., Methods: Newborn rats received subcutaneous injections of either morphine or equal volume of saline twice daily for the first two weeks of life. In adulthood, animals received an additional two weeks of saline or morphine injections before undergoing structural brain MRI. After completion of treatment, structural T2-weigthed MRI images were acquired on a 7 T preclinical scanner (Bruker) using a RARE FSE sequence. Total and regional brain volumes were manually extracted from the MRI images using ITK-SNAP (v.3.6). Regions of interest included the brainstem, the cerebellum, as well as the forebrain and its components: the cerebral cortex, hippocampus, and deep gray matter (including basal ganglia, thalamus, hypothalamus, ventral tegmental area). Absolute (cm 3 ) and normalized (as % total brain volume) values were compared using a one-way ANOVA with Tukey HSD post-hoc test., Results: Prolonged morphine administration in infancy was associated with lower body weight and globally smaller brain volumes, which was not different between the sexes. In adulthood, females had lower body weights than males, but no difference was observed in brain volumes between treatment groups. Our results are suggestive of no long-term effect of prolonged morphine treatment in infancy with respect to body weight and brain size in either sex. Interestingly, prolonged morphine administration in adulthood was associated with smaller brain volumes that differed by sex only in case of previous exposure to morphine in infancy. Specifically, we report significantly smaller total brain volume of female rats on account of decreased volumes of forebrain and cortex., Conclusions: Our study provides insight into the short- and long-term consequences of prolonged morphine administration in an infant rat model and suggests brain vulnerability to subsequent exposure in adulthood that might differ with sex., 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., (© 2023 Taylor, Cheng, Hodkinson, Afacan, Zurakowski and Bajic.)

Management of breast cancer in limited-resource settings is hindered by a lack of low-cost, logistically sustainable approaches toward molecular and cellular diagnostic pathology services that are needed to guide therapy. To address these limitations, we have developed a multimodal cellphone-based platform-the EpiView-D4-that can evaluate both cellular morphology and molecular expression of clinically relevant biomarkers directly from fine-needle aspiration (FNA) of breast tissue specimens within 1 h. The EpiView-D4 is comprised of two components: (1) an immunodiagnostic chip built upon a "non-fouling" polymer brush-coating (the "D4") which quantifies expression of protein biomarkers directly from crude cell lysates, and (2) a custom cellphone-based optical microscope ("EpiView") designed for imaging cytology preparations and D4 assay readout. As a proof-of-concept, we used the EpiView-D4 for assessment of human epidermal growth factor receptor-2 (HER2) expression and validated the performance using cancer cell lines, animal models, and human tissue specimens. We found that FNA cytology specimens (prepared in less than 5 min with rapid staining kits) imaged by the EpiView-D4 were adequate for assessment of lesional cellularity and tumor content. We also found our device could reliably distinguish between HER2 expression levels across multiple different cell lines and animal xenografts. In a pilot study with human tissue (n = 19), we were able to accurately categorize HER2-negative and HER2-positve tumors from FNA specimens. Taken together, the EpiView-D4 offers a promising alternative to invasive-and often unavailable-pathology services and may enable the democratization of effective breast cancer management in limited-resource settings.

We carried out this meta-analysis for the aim of exploring the influence of diabetes mellitus (DM) on the prognosis of patients with ischemic stroke. Relevant studies were identified using computerized databases supplemented with manual search strategies. The included studies were strictly followed the inclusion and exclusion criteria. Case-control studies which related to the influence of DM on the prognosis of patients with ischemic stroke were selected. Statistical analyses were implemented with the STATA version 12.0 statistical software. Our current meta-analysis initially retrieved 253 studies (227 in Chinese and 26 in English), 13 studies (6 in English and 7 in Chinese) were eventually incorporated in this meta-analysis. These 13 case-control studies included 8463 patients altogether (3249 patients with DM complicated with ischemic stroke and 5214 patients with ischemic stroke). The results of this meta-analysis manifested that there was a significant difference of the blood glucose level at 48 h after stroke between patients with DM complicated with ischemic stroke and patients with ischemic stroke (standard mean difference [SMD] =1.27, 95% confidence interval [CI] =0.02-2.51, P = 0.047); however, the effectiveness, fatality, and the National Institutes of Health Stroke Scale (NIHSS) score in patients with DM complicated with ischemic stroke, and patients with ischemic stroke had no significant difference (effectiveness: risk ratio [RR] = 0.88, 95% CI = 0.75-1.03, P = 0.121; fatality: RR = 1.29, 95% CI = 0.97-1.71, P = 0.081; NIHSS score: SMD = -0.14, 95% CI = -1.56-1.28, P = 0.849). The current evidence suggests that there is statistical difference of the blood glucose level at 48 h after stroke between patients with DM complicated with ischemic stroke and patients with ischemic stroke, but there is no statistical difference of prognostic indicators between patients in two groups. Thus, our study provides certain clinical value., Competing Interests: There are no conflicts of interest.

Objective: The aim of this study is to investigate the clinical effect of goal-directed fluid therapy in elderly patients with radical resection of bladder cancer., Materials and Methods: Seventy-six elderly patients with radical resection of bladder cancer were selected from October 2012 to October 2014 and randomly divided into two groups, in which 38 patients received routine treatment as the control group and 38 patients received goal-directed fluid therapy based on routine treatment as the observation group. The treatment effect was compared between two groups., Results: The cardiac index, stroke volume variability, mean arterial pressure, central venous pressure, central venous oxygen saturation, oxygen supply index, oxygen consumption index, and oxygen uptake rate in observation group were distinctly higher than those in control group at T 1 , T 2 , T 3 , and T 4 while the artery serum lactate and S100-β were apparently lower than those in control group at T 1 , T 2 , T 3 , and T 4 . The urine volume and colloidal infusion were obviously elevated when compared with those in control group at T 1 , T 2 , T 3 , and T 4 while the crystalloid infusion volume, total liquid infusion volume, hospitalization time, and expenses were significantly less than those in control group; further, similar tendency was also found regarding the complication incidences of nausea, vomiting, or hypotension in observation group. The postoperative flatus and postoperative food-taking times were visibly earlier than those in control group (both P < 0.05)., Conclusion: The goal-directed fluid therapy is beneficial for stabilization of hemodynamic status and maintenance of oxygen balance of supply and demand, and it is worthy of clinical expansion for good microcirculation perfusion, reduction in therapeutic time and expenses of patients, and less complications and superior security., Competing Interests: There are no conflicts of interest

Background/aims: Erinacine, which is extracted from the medicinal mushroom Hericium erinaceus, is known to play anticancer roles in human cancers. The following study aims to investigate the role of erinacine in the opening of the mitochondrial permeability transition pore (MPTP) in hepatocellular carcinoma (HCC) through the PI3K/Akt/GSK-3β signaling pathway and highlights the applicability of erinacine in HCC treatments., Methods: HCC and paracancerous tissues were obtained from 85 HCC patients who've undergone surgical resection. Immunohistochemistry was adopted to detect positive expression of PI3K, Akt, and GSK-3β. Treatment of HepG-2 with LY294002 (an inhibitor of the PI3K/Akt/GSK-3β signaling pathway) and different concentration of erinacine was performed to determine the involvement of LY294002 in erinacine action. The expressions of PI3K, Akt, GSK-3β, CyclinD1, Vimentin, β-catenin, Bcl-2, E-cadherin, Bax, and caspase-9 were determined by RT-qPCR and Western blot analysis. Cell viability, colony formation rate, migration, invasion, cycle, and apoptosis were detected by MTT, colony formation, wound healing assay, Transwell assay, and flow cytometry, respectively. The size and weight of xenograft tumors were observed in nude mice. Mitochondrial membrane potential in HepG-2 was determined using laser scanning confocal microscopy following JC-1 staining. Mitochondrial Ca2+ indicator Rhod-2, AM was used to detect the changes of mitochondrial Ca2+, while western blot analysis was employed to detect the presence levels of cytochrome C (cyt-C)., Results: The results revealed that PI3K, Akt, and GSK-3β were up-regulated in HCC tissues. Erinacine or LY294002 led to a decrease in mitochondrial membrane potential, increase in intracellular mitochondrial Ca2+, and the release of cyt-C in mitochondria. In addition, Erinacine was found to decrease the mitochondrial membrane potential, expression of PI3K, Akt, GSK-3β, CyclinD1, Vimentin, β-catenin, and Bcl-2, cell proliferation, colony formation ability, migration, invasion, and xenograft tumor size, while E-cadherin, Bax, and caspase-9 expression, and cell apoptosis were elevated in a dose-dependent manner. Erinacine also stimulated the effects of LY294002 on the HCC. Following the addition of 500 μM Erinacine and MPTP opening inhibitor CsA, we found that the mitochondrial membrane potential level increased, while mitochondrial Ca2+ and Cyt-C decreased from the mitochondria., Conclusion: The results from the study demonstrated that erinacine induced MPTP opening, facilitates the release of cyt-C, and inhibited cell proliferation, migration, and invasion, while it promotes apoptosis by inactivating the PI3K/Akt/GSK-3β signaling pathway, preventing the progression of HCC., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

We aim to investigate the effects of sevoflurane on the ATPase activity of the hippocampal neurons in rats with cerebral ischemia-reperfusion injury (IRI) via the cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) signaling pathway. Sixty rats were assigned into the normal, model and sevoflurane groups (n = 20, the latter two groups were established as focal cerebral IRI models). The ATPase activity was detected using an ultramicro Na (+)-K (+)-ATP enzyme kit. Immunohistochemical staining was used to detect the positive protein expression of cAMP and PKA. The hippocampal neurons were assigned to the normal, IRI, IRI + sevoflurane, IRI + forskolin, IRI + H89 and IRI + sevoflurane + H89 groups. qRT-PCR and Western blotting were performed for the expressions of cAMP, PKA, cAMP-responsive element-binding protein (CREB) and brain derived neurotrophic factor (BDNF). The normal and sevoflurane groups exhibited a greater positive protein expression of cAMP and PKA than the model group. Compared with the normal group, the expressions of cAMP, PKA, CREB and BDNF all reduced in the IRI, model and IRI + H89 groups. The sevoflurane group showed higher cAMP, PKA, CREB and BDNF expressions than the model group. Compared with the IRI group, ATPase activity and expressions of cAMP, PKA, CREB and BDNF all increased in the normal, IRI + sevoflurane and IRI + forskolin groups but decreased in the IRI + H89 group. It suggests that sevoflurane could enhance ATPase activity in hippocampal neurons of cerebral IRI rats through activating cAMP-PKA signaling pathway., (Copyright © 2017. Published by Elsevier Taiwan.)

Background: Carnosol is an ortho-diphenolic diterpene with excellent antioxidant potential. The present study was designed to identify the protective role of carnosol against spinal cord injury (SCI)-induced oxidative stress and inflammation in Wistar rats., Methods: In the present study, oxidative stress status was determined through estimating total antioxidant capacity, total oxidant status, lipid peroxide content, protein carbonyl and sulfhydryl levels, reactive oxygen species (ROS), antioxidant status (superoxide-dismutase, catalase, glutathione, glutathione peroxidase, glutathione-S-transferase). Inflammatory effects were determined by analyzing the expression of NF-κB and COX-2 through Western blot analysis. Further, carnosol-mediated redox homeostasis was analyzed by determining p-AKT and Nrf-2 levels., Results: SCI resulted in a significant increase in oxidative stress status through increased ROS generation, total oxidant levels, lipid peroxide content, protein carbonyl and sulfhydryl levels. The antioxidant status in SCI rats was significantly reduced, indicating imbalance in redox status. In addition, the expression of NF-κB and COX-2 was significantly upregulated, while p-AKT and Nrf-2 levels were downregulated in SCI rats. However, treatment with carnosol showed a significant enhancement in the antioxidant status with concomitant decline in oxidative stress parameters. Further, carnosol treatment regulated the key proteins in inflammation and redox status through significant downregulation of NF-κB and COX-2 levels and upregulation of p-AKT and Nrf-2 expression., Conclusion: Thus, the present study shows for the first time on the protective role of carnosol against SCI-induced oxidative stress and inflammation through modulating NF-κB, COX-2 and Nrf-2 levels in Wistar rats.

There are many barriers to healthcare for the general population that has been documented throughout the years, with one particularly affected group being individuals with disabilities. One identified healthcare barrier for individuals with disabilities is the inability to gain access to the healthcare system through health insurance. While many attempts have been made to resolve this issue, serious problems have yet to be resolved. The Patient Protection Affordable Care Act (PPACA) attempted to solve the issue by expanding Health Insurance Portability and Accountability Act of 1996's (HIPAA) current regulations on employee wellness programs. The relevant regulations govern employee wellness programs to allow employers to offer their employees greater incentives for meeting employer-defined health targets. This expansion has an adverse effect because it disadvantages groups like individuals with disabilities by penalizing them through higher premiums or cost sharing when they are unable to meet wellness targets. This article argues PPACA's requirement for employee wellness programs provides additional barriers to healthcare insurance for individuals with disabilities. Part I of this Comment describes how the healthcare industry discriminates against individuals with disabilities by continuing to deny them meaningful access to healthcare through payment of higher premiums. Part II examines how the wellness program provision allows employers to shift the cost of medical coverage to the employee for failure to participate in the wellness program. Part III summarizes how the ADA's reasonable requirement places an obligation on employers to make reasonable accommodation to individuals with disabilities, which will improve the health of working individuals with disabilities. Part IV concludes with suggestions for further reform., (Copyright by Cleveland State University.)

Pelvic pain and vaginal bleeding are common complaints in pregnant women presenting to emergency department. Cervical ectopic pregnancy (EP) is a rare type of EP, with a higher likelihood of complications if missed. Its sonographic findings can be difficult to distinguish from normal pregnancy or an abortion in progress. In this report, we present a rare case of a cervical EP, diagnosed using bedside ultrasonography, and characterize the pitfalls associated with its diagnosis.

Common bile duct stones frequently accompany gallstones and can be identified by a variety of imaging modalities. Little is known about the time course of dilatation of the common bile duct after acute obstruction or of normalization after spontaneous passage of an obstructing stone. We describe a case showing rapid fluctuations in common bile duct diameter during 72 hours in a patient presenting with epigastric pain and vomiting. Initial emergency bedside ultrasonography revealed a distended gallbladder, a dilated common bile duct (17 mm), and an obstructing stone. Five hours later, ultrasonography performed in the radiology suite showed a normal common bile duct diameter (4 mm) and no obstructing stone. The patient was admitted, and during the course of hospitalization different imaging modalities reported fluctuations in common bile duct measurements, ranging from 4 mm on computed tomography to 14 mm on endoscopic retrograde cholangiopancreatography. This case demonstrates disappearance of an obstructing stone with normalization of a highly distended common bile duct during 5 hours, highlighting that gallstone disease may be highly dynamic, with the possibility of rapid changes of common bile duct diameter. Emergency physicians, who frequently depend on ultrasonography to diagnose biliary disease, should be wary of the potential for rapid changes of sonographic findings in these patients., (Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Sphingosine 1-phosphate (S1P), a sphingolipid metabolite that plays an important role in the regulation of cell survival, growth, migration, and angiogenesis, acts both inside the cells and as an extracellular mediator through binding to five G protein-coupled receptors (S1P(1-5)). Sphingosine kinase 1 (SK1), the enzyme responsible for S1P production, is overexpressed in many solid tumors, including gliomas. One common feature of these tumors is the presence of "hypoxic regions," characterized by cells expressing high levels of hypoxia-inducible factors HIF-1alpha and HIF-2alpha, two transcription regulators that modulate the levels of proteins with crucial roles in tumor progression. So far, nothing is known about the role and the regulation of SK1 during tumor-induced hypoxia or about SK1 regulation and HIFs. Here we investigated the role of HIF-1alpha and HIF-2alpha in the regulation of SK1 during hypoxic stress in glioma-derived U87MG cells. We report that hypoxia increases SK1 mRNA levels, protein expression, and enzyme activity, followed by intracellular S1P production and S1P release. Interestingly, knockdown of HIF-2alpha by small interfering RNA abolished the induction of SK1 and the production of extracellular S1P after CoCl(2) treatment, whereas HIF-1alpha small interfering RNA resulted in an increase of HIF-2alpha and of SK1 protein levels. Moreover, using chromatin immunoprecipitation analysis, we demonstrate that HIF-2alpha binds the SK1 promoter. Functionally, we demonstrate that conditioned medium from hypoxia-treated tumor cells results in neoangiogenesis in human umbilical vein endothelial cells in a S1P receptor-dependent manner. These studies provide evidence of a link between S1P production as a potent angiogenic agent and the hypoxic phenotype observed in many tumors.

Objective: To observe the distribution character of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in Chinese population and its relationship with essential hypertension., Methods: Polymerase chain reaction (PCR) technique was used to detect the angiotensin converting enzyme gene I/D polymorphism in 2966 subjects of Kailuan Coal Mine, and further restriction analysis was performed., Results: The frequencies of ACE II, ID, DD genotypes in total study population were 41.5%, 38.4%, 20.1%, respectively. The DD genotypes in hypertensive group and that in control group were 18.9% and 21.0%, respectively. There was no significant difference between hypertensive group and control group (P>0.05). The same result was seen after stratification by age and gender in each group, respectively(P>0.05). The DD genotype and D allele showed a tendency to decrease with the increase of age (P<0.001)., Conclusion: The above results suggested that essential hypertension was not associated with ACE I/D polymorphism. The distributions of ACE genotype and allele varied with age, and the subjects with the character of DD genotype were at higher risk of early death.

Imipenem/cilastatin sodium is a new thienamycin class of antibiotic with a broad spectrum of bactericidal activities. It may be a suitable single first-line therapy for the treatment of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. Fifty episodes of CAPD peritonitis were treated with imipenem/cilastatin sodium. On presentation, all patients were given an intravenous loading dose of 1 g of imipenem/cilastatin sodium followed by intraperitoneal imipenem/cilastatin sodium for 10 days. During 1989 (30 episodes), 20 mg imipenem/cilastatin sodium was added to each 2-liter bag of peritoneal dialysis (PD) fluid for 10 days. The primary response rate as defined by polymorphonuclear neutrophils < 100/ml in PD fluid was 90%. Unfortunately, 17% of the peritonitis relapsed within 14 days of stopping antibiotic. The complete cure rate without relapse was therefore 73%. During 1990 (20 episodes), 100 mg imipenem/cilastatin sodium was added to each 2-liter bag of PD fluid for 10 days. The primary response rate was 95%, the complete cure rate without relapse was 85%. Imipenem/cilastatin sodium is an effective single first-line antibiotic for the treatment of peritonitis in CAPD.