Clinicopathologic Spectrum of Lysozyme-Associated Nephropathy.
Lysozyme-associated nephropathy (LyN), a rare cause of kidney injury in patients with chronic myelomonocytic leukemia (CMML), has not been well described to date. We report the clinicopathologic spectrum of LyN from a multi-institutional series. We identified 37 native kidney biopsies with LyN and retrospectively obtained clinicopathologic data. Thirty-seven patients had a median age of 74 years and included 78% males. Their most common presentation was acute kidney injury (AKI) or AKI on chronic kidney disease (CKD) (66%) with median estimated glomerular filtration rate (eGFR) of 21.7 ml/min per 1.73 m2, and proteinuria of 1.7 g. A minority (15%) had partial Fanconi syndrome. Serum lysozyme levels were elevated in all tested. Hematologic disorder (n = 28, 76%) was the most common etiology, including CMML (n = 15), acute myeloid leukemia (n = 5), and myelodysplastic syndrome (MDS) (n = 5). Nonhematologic causes (n = 5, 14%), included metastatic neuroendocrine carcinoma (n = 3), sarcoidosis, and leprosy. Etiology was unknown in 4 (11%). Pathology showed proximal tubulopathy with abundant hypereosinophilic intracytoplasmic inclusions, with characteristic staining pattern by lysozyme immunostain. Mortality was high (8/30). However, among the 22 alive, including 85% treated, 7 had improved kidney function, including 1 who discontinued dialysis and 6 with increase in eGFR >15 ml/min per 1.73 m2 compared with eGFR at the time of biopsy. Increased awareness of the full clinicopathologic spectrum of LyN may lead to prompt diagnosis, earlier treatment, and potentially improved outcome of this rare entity.


The association between early autistic traits and psychotic experiences in adolescence.
There has been growing interest in the clinical and biological links between autistic spectrum disorder and psychotic disorders, and between symptoms of these disorders that exist below diagnostic thresholds. Whilst autism and schizophrenia are regarded as distinct disorders, recent studies support an overlap in the genetic architecture across these conditions. Although early neurodevelopmental impairment is associated with psychotic disorders in later life, evidence from longitudinal studies of the relationship between autistic traits and psychotic experiences is limited. Aims The aim of the study is to explore whether children with early autistic traits (social interaction and communication problems, and restricted, repetitive interests and behaviours) are more likely to present with psychotic experiences in early adolescence. Longitudinal study using the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. The mothers of 8232 children were asked about autistic traits in their children as part of the Development and Well-Being Assessment (DAWBA) at the age of 7. Of those, 6439 children completed a semi-structured clinical assessment for psychotic experiences at the age of 12. Children whose mothers had concerns about autistic traits in early life, in particular with regard to speech development or 'rituals'/'habits', were more likely to develop psychotic experiences in early adolescence. The greater the number of early autistic traits a child had, the greater their risk of developing psychotic experiences. These associations were not confounded by IQ, family history of depression or schizophrenia, gender or socio-demographic characteristics. Childhood autistic traits, and particularly speech problems and odd rituals or unusual habits, are associated with psychotic experiences in adolescence. This may be a result of a shared aetiology or because autistic traits may also be an early precursor of psychotic experiences.


Cataract surgery following refractive surgery: Principles to achieve optical success and patient satisfaction.
A growing number of patients with prior refractive surgery are now presenting for cataract surgery. Surgeons face a number of unique challenges in this patient population that tends to be highly motivated to retain or regain functional uncorrected acuity postoperatively. Primary challenges include recognition of the specific type of prior surgery, use of appropriate intraocular lens (IOL) power calculation formulas, matching IOL style with spherical aberration profile, the recognition of corneal imaging patterns that are and are not compatible with toric and/or presbyopia-correcting lens implantation, and surgical technique modifications, which are particularly relevant in eyes with prior radial keratotomy or phakic IOL implantation. Despite advancements in IOL power formulae, corneal imaging, and IOL options that have improved our ability to achieve targeted postoperative refractive outcomes, accuracy and predictability remain inferior to eyes that undergo cataract surgery without a history of corneal refractive surgery. Thus, preoperative evaluation of patients who will and will not be candidates for postoperative refractive surgical enhancements is also paramount. We provide an overview of the specific challenges in this population and offer evidence-based strategies and considerations for optimizing surgical outcomes.


Cancer Survivors and the Patient-Centered Medical Home.
Survivor care plans have been described as useful tools for enhancing the quality of follow-up care that cancer survivors receive after their active treatment has been completed. The relative success of current survivor care plan models is strongly dependent on the actions of individual patients. In this qualitative study of 33 cancer survivors, we explored patients' understanding of follow-up care and their motivations and resources for seeking care. Three types of survivor experiences were identified from narratives of patients treated in community oncology and NCI designated comprehensive cancer centers, ranging from non-activated patients who need enhanced health care communication and decision support to navigate their care to highly activated patients adept at navigating complex health care settings. Using the Patient-Centered Medical Home as a conceptual framework, we propose a research, policy and practice agenda that advocates for multi-faceted decision support to enhance cancer survivorship and follow-up care.


Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K(2P)) and voltage-gated (K(v)1.1 and K(v)1.2) potassium channels.
Imiquimod (IQ) is known as an agonist of Toll-like receptor 7 (TLR7) and is widely used to treat various infectious skin diseases. However, it causes severe itching sensation as its side effect. The precise mechanism of how IQ causes itching sensation is unknown. A recent report suggested a molecular target of IQ as TLR7 expressed in dorsal root ganglion (DRG) neurons. However, we recently proposed a TLR7-independent mechanism, in which the activation of TLR7 is not required for the action of IQ in DRG neurons. To resolve this controversy regarding the involvement of TLR7 and to address the exact molecular identity of itching sensation by IQ, we investigated the possible molecular target of IQ in DRG neurons. When IQ was applied to DRG neurons, we observed an increase in action potential (AP) duration and membrane resistance both in wild type and TLR7-deficient mice. Based on these results, we tested whether the treatment of IQ has an effect on the activity of K(+) channels, K(v)1.1 and K(v)1.2 (voltage-gated K(+) channels) and TREK1 and TRAAK (K(2P) channels). IQ effectively reduced the currents mediated by both K(+) channels in a dose-dependent manner, acting as an antagonist at TREK1 and TRAAK and as a partial antagonist at K(v)1.1 and K(v)1.2. Our results demonstrate that IQ blocks the voltage-gated K(+) channels to increase AP duration and K(2P) channels to increase membrane resistance, which are critical for the membrane excitability of DRG neurons. Therefore, we propose that IQ enhances the excitability of DRG neurons by blocking multiple potassium channels and causing pruritus.


Photo-Induced Electron Transfer-Triggered Structure Deformation Promoting Near-Infrared Photothermal Conversion for Tumor Therapy.
Photothermal therapy (PTT) is a promising approach to cancer treatment. Heptamethine cyanine (Cy7) is an attractive photothermal reagent because of its large molar absorption coefficient, good biocompatibility, and absorption of near-infrared irradiation. However, the photothermal conversion efficiency (PCE) of Cy7 is limited without ingenious excitation-state regulation. In this study, the photothermal conversion ability of Cy7 is efficiently enhanced based on photo-induced electron transfer (PET)-triggered structural deformation. Three Cy7 derivatives, whose Cl is replaced by carbazole, phenoxazine, and phenothiazine at the meso-position (CZ-Cy7, PXZ-Cy7, and PTZ-Cy7), are presented as examples to demonstrate the regulation of the energy release of the excited states. Because the phenothiazine moiety exhibits an obvious PET-induced structural deformation in the excited state, which quenches the fluorescence and inhibits intersystem crossing of S1 →T1 , PTZ-Cy7 exhibits a PCE as high as 77.5%. As a control, only PET occurs in PXZ-Cy7, with a PCE of 43.5%. Furthermore, the PCE of CZ-Cy7 is only 13.0% because there is no PET process. Interestingly, PTZ-Cy7 self-assembles into homogeneous nanoparticles exhibiting passive tumor-targeting properties. This study provides a new strategy for excited-state regulation for photoacoustic imaging-guided PTT with high efficiency.


Transepithelial transport and accumulation of flavone in human intestinal Caco-2 cells.
Flavonoids are found in many food items of plant origin. Intake of flavonoids has been linked to the prevention of human diseases including cancer. However, little is known about the intestinal absorption of flavonoids in the cellular level. This study was designed to study the absorption of dietary flavonoids using cultured human intestinal epithelial cell monolayer as a model system and 14C-flavone as a model compound. 14C-flavone at 10 microM was found to move across the cell monolayer rapidly both from the luminal to basolateral direction and from the basolateral to luminal direction. The rate of transport from the luminal to basolateral direction was 5 times of the rate for phenylalanine, an aromatic amino acid. Flavone also accumulated substantially in the cells. Replacing sodium in the transport buffer with potassium did not affect the transport but reducing the incubation temperature significantly decreased the initial rate of transport. The presence of protein in the transport buffer reduced the initial rate of transport to half. Other flavonoids and hydrophobic chemicals at 100 microM had no effects on the transport. Together with the evidence from microscopic observation (Cancer Letts. 110: 41-48, 1996), this study supports that rapid diffusional transport may be the main route for flavonoid absorption. The ability of intestinal cells to accumulate flavone is consistent with the role of flavonoids in colon cancer prevention.


Accounting for variation in length of NICU stay for extremely low birth weight infants.
To develop a length of stay (LOS) model for extremely low birth weight (ELBW) infants. We included infants from the California Perinatal Quality Care Collaborative with birth weight 401 to 1000 g who were discharged to home. Exclusion criteria were congenital anomalies, surgery and death. LOS was defined as days from admission to discharge. As patients who died or were transferred to lower level of care were excluded, we assessed correlation of hospital mortality rates and transfers to risk-adjusted LOS. There were 2012 infants with median LOS 79 days (range 23 to 219). Lower birth weight, lack of antenatal steroids and lower Apgar score were associated with longer LOS. There was negligible correlation between risk-adjusted LOS and hospital mortality rates (r=0.0207) and transfer-out rates (r=0.121). Particularly because ELBW infants have extended hospital stays, identification of unbiased and informative risk-adjusted LOS for these infants is an important step in benchmarking best practice and improving efficiency in care.


Expanding Criteria in Controlled Cardiac Death Donors: Now With 70-Year-Old Donors.
Outcomes of kidney transplant (KT) after controlled cardiac death with older donors are under review. We aimed to analyze early and midterm clinical outcomes using older (≥70 years) controlled cardiac death donors (cDCD). Retrospective observational single-center study including all KTs from donors ≥70 years from cDCD and donors after brain death (DBD) performed from January 2017 to January 2022. We performed a comparative study between the 2 groups (cDCD and DBD). An analysis of clinical characteristics, early clinical outcomes, and patient and graft survival rates was made. We included 25 cDCD KTs and 63 DBD KTs ≥70 years. The median follow-up was 18.7 months. Recipients from cDCD were more comorbid. Donors from DBD showed higher hypertension and stroke rate. The KTs from older cDCD showed similar delayed graft function rate (cDCD: 34.6% vs DBD extended criteria donor: 35.3%, P = .59) and primary nonfunction (cDCD 16% vs DBD 17.4%, P = .85) compared with older DBD. Medium (3 years) graft death-censored survival was satisfying (cDCD 73% vs DBD 72%) despite a relevant early graft failure rate in both groups (cDCD 16% vs DBD 23%, P = .26). No differences were observed in patient survival at year 1 (cDCD 94% vs DBD 93%, P = .62). In our series, the outcomes with older cDCD are similar compared with older DBD. Although older donors showed an increase of early graft failure, these kidneys allowed us to maximize the opportunities for candidates that otherwise should remain on dialysis.


The impact of chronic pain on adolescents: a review of previously used measures.
To review the use of instruments to assess the impact of adolescent chronic pain, focussing on the development of instruments, the domains covered, psychometric properties, and published use with adolescent chronic pain patients. Systematic literature searching recovered 706 articles, yielding 116 relevant articles, employing a total of 43 separate measurement instruments, which were subjected to content analysis. Most instruments were in the psychological domain (n = 22), with a self-report format (n = 36). Thirty instruments were specifically developed for adolescent populations; only 12 instruments had psychometric evaluation with adolescent chronic pain patients. The median use of any one instrument in published studies was two. Clinically relevant psychometric data were missing for many instruments. There is a diversity of instrumentation with some pockets of depth of use, but some domains of chronic pain experience with no routine assessment. Further development of the knowledge base of measurement of the impact of chronic adolescent pain is necessary.


Fasciotomy on a female patient with acquired factor VIII: A case report and literature review of management.
Acquired factor VIII inhibitors can be a rare cause of extensive intramuscular bleeding requiring fasciotomy. The subsequent postoperative period requires close monitoring due to high risk of fatal blood loss. Acquired factor VIII inhibitors are a rare cause of often extensive bleeding and subsequently large hematomas. This disorder's overall mortality can reach 38%, largely due to immunosuppression and subsequent infections or an underlying cause such as malignancy. The patient in this case study presented with a hematoma and extensive ecchymosis of the hand and forearm, which continued to progress, precipitating compartment syndrome of the hand and forearm and ultimately requiring fasciotomy. The combination of factors led to significant blood loss in the postoperative period requiring major fluid resuscitation and intensive care unit (ICU) level care. Due to this disorder's rarity and overall mortality, we present this case report with a literature review for management of acquired hemophilia in the setting of urgent fasciotomy.


Engineering strategy of yeast metabolism for higher alcohol production.
While Saccharomyces cerevisiae is a promising host for cost-effective biorefinary processes due to its tolerance to various stresses during fermentation, the metabolically engineered S. cerevisiae strains exhibited rather limited production of higher alcohols than that of Escherichia coli. Since the structure of the central metabolism of S. cerevisiae is distinct from that of E. coli, there might be a problem in the structure of the central metabolism of S. cerevisiae. In this study, the potential production of higher alcohols by S. cerevisiae is compared to that of E. coli by employing metabolic simulation techniques. Based on the simulation results, novel metabolic engineering strategies for improving higher alcohol production by S. cerevisiae were investigated by in silico modifications of the metabolic models of S. cerevisiae. The metabolic simulations confirmed that the high production of butanols and propanols by the metabolically engineered E. coli strains is derived from the flexible behavior of their central metabolism. Reducing this flexibility by gene deletion is an effective strategy to restrict the metabolic states for producing target alcohols. In contrast, the lower yield using S. cerevisiae originates from the structurally limited flexibility of its central metabolism in which gene deletions severely reduced cell growth. The metabolic simulation demonstrated that the poor productivity of S. cerevisiae was improved by the introduction of E. coli genes to compensate the structural difference. This suggested that gene supplementation is a promising strategy for the metabolic engineering of S. cerevisiae to produce higher alcohols which should be the next challenge for the synthetic bioengineering of S. cerevisiae for the efficient production of higher alcohols.


Modeling the change trajectory of sleep duration and its associated factors: based on an 11-year longitudinal survey in China.
Sleep duration is a vital public health topic, yet most existing studies have been limited to cross-sectional surveys or inconsistent classifications of sleep duration categories, and few characterized its continuous development process. The current study aimed to depict its change trajectory in the general population and identify associated factors from a dynamic perspective. A total of 3788 subjects (45.4% male, mean age 46.72 ± 14.89 years) from the China Health and Nutrition Survey were recruited, and their daily sleep duration for five consecutive measurements from 2004 to 2015 was recorded. We adopted latent growth modelling to establish systematic relations between sleep duration and time. Participants' sociodemographic characteristics, lifestyle, and health factors were taken as covariates. The change in sleep duration could be depicted by a linear decreasing trajectory with the mean yearly decrease at 2.5 min/day. The trajectory did not differ by residence, BMI category, chronic disease situation, smoking status, or drinking status. Moreover, there were sex and age differences in the trajectory, and females and those under 30 were prone to larger decrease rates. The quantified yearly change in sleep duration provided insights for the prediction and early warning of insufficient sleep. Public health interventions focusing on slowing down the decrease rates among females and young individuals are warranted.


Retinal damage related to high-intensity light-emitting diode exposure: An in vivo study.
The objective of this investigation was to evaluate the effects of high-intensity light-emitting diode (LED) light from a curing device on the retinas of Wistar rats. Six male Wistar rats were used, and their ocular structures were the focus of this study. During the photostimulation of each animal, the right eye of the animal, considered the control sample, was covered with a removable polyvinyl chloride cap, and the contralateral eye, the experimental sample, was exposed to high-intensity LED light, 3200 mW/cm2 (VALO Ortho; Ultradent Products, South Jordan, Utah) for 144 seconds from a distance of 30 cm. The animals were exposed to the LED light 3 times on the same day to investigate if any acute inflammatory changes in the retina occurred. Seven days after the photostimulation sessions, the animals were anesthetized and perfused with paraformaldehyde solution. After which, the eyes were resected and processed histologically. The histologic sections were analyzed stereologically and histomorphometrically to measure the parameters of the retina under investigation. There was a statistically significant increase in total retinal volume in the experimental group because of the increased volume of the ganglion cell layers, inner plexiform layers, outer nuclear layers, and the cone and rod extensions. There was no statistically significant difference in terms of density. However, there was a statistically significant increase in the nuclear area of the cells in all the studied layers in the group exposed to high-intensity LED light. In addition, hyperchromatic cells that are suggestive of pyknosis were observed. An acute but short protocol of exposure of high-intensity LED light to the eye caused morphometric alterations in the retinal structures, specifically in the nuclear area of the photosensitive cells.


Heterologous Expression of the Leuconostoc Bacteriocin Leucocin C in Probiotic Yeast Saccharomyces boulardii.
The yeast Saccharomyces boulardii is well known for its probiotic effects such as treating or preventing gastrointestinal diseases. Due to its ability to survive in stomach and intestine, S. boulardii could be applied as a vehicle for producing and delivering bioactive substances of interest to human gut. In this study, we cloned the gene lecC encoding the antilisterial peptide leucocin C from lactic acid bacterium Leuconostoc carnosum in S. boulardii. The constructed S. boulardii strain secreted a peptide, which had molecular weight corresponding to leucocin C in SDS-PAGE. The peptide band inhibited Listeria monocytogenes in gel overlay assay. Likewise, concentrated S. boulardii culture supernatant inhibited the growth of L. monocytogenes. The growth profile and acid tolerance of the leucocin C secreting S. boulardii were similar as those of the strain carrying the empty vector. We further demonstrated that the cells of the leucocin C producing S. boulardii efficiently killed L. monocytogenes, also without antibiotic selection pressure. These results showed that antilisterial activity could be added to the arsenal of probiotic activities of S. boulardii, demonstrating its potential as a carrier for therapeutics delivery.


Conduction Recovery After Cavotricuspid Isthmus Ablation When Performed With or Without Concomitant Atrial Fibrillation Ablation.
This study sought to define the association between conduction recovery across the cavotricuspid isthmus (CTI) and typical atrial flutter (AFL) recurrence when CTI ablation is performed with pulmonary vein isolation (PVI) compared with a stand-alone procedure. CTI ablation is commonly performed at the same time as PVI to treat AFL or as an empiric therapy. Conduction recovery is a recognized problem after linear ablation in the left atrium (e.g., mitral isthmus ablation) and is proarrhythmic. Less is known about conduction recovery after CTI ablation and possible differences in outcomes when performed at the time of PVI compared with at the time of a stand-alone procedure. Eligible participants who underwent stand-alone CTI ablation were compared with those who underwent a combined (CTI+PVI) procedure. CTI conduction recovery was assessed at the time of a second ablation. Conduction recovery across the CTI (primary outcome) and recurrence of typical AFL (secondary outcome) were studied using multivariable logistic regression. Among 295 eligible participants (median age: 64 years [interquartile range: 55 to 69 years]; 33% women), recovery was assessed in 232 and was more common after combined versus stand-alone CTI ablation (52% [72 of 139] vs. 13% [12 of 93]; p < 0.001). In multivariable analysis, CTI ablation performed as a combined procedure increased odds of CTI conduction recovery 7.8-fold (odds ratio: 7.8; 95% confidence interval: 3.3 to 18.3; p < 0.001) and clinical AFL recurrence 4.1-fold (odds ratio: 4.1; 95% confidence interval: 1.0 to 16.9; p = 0.049). CTI ablation performed at the time of atrial fibrillation ablation is associated with higher rates of conduction recovery and typical flutter recurrence.


Polyamine-mediated conformational perturbations in DNA alter the binding of estrogen receptor to poly(dG-m5dC).poly(dG-m5dC) and a plasmid containing the estrogen response element.
The binding estrogen receptor (ER) to the upstream regions of estrogen-responsive genes, the estrogen response elements (ERE), is of fundamental importance in the regulation of gene expression by estradiol. Multiple cell-specific factors affect ER-ERE binding and modulate the responses of estradiol. We studied the role of polyamines in the recognition of ER, a ligand-activated transcription factor, with a left-handed Z-DNA forming polynucleotide as well as with a plasmid containing ERE. Polyamines are cellular organic cations with multiple functions in cell growth and differentiation. Polyamines induce Z-DNA conformation in alternating purine-pyrimidine sequences. To understand the role of polyamine-induced DNA conformational transition in ER-DNA interaction, we studied the binding of partially purified rabbit uterine ER to poly(dG-m5dC).poly(dG-m5dC). The induction of Z-DNA in the polynucleotide was monitored by circular dichroism and ultraviolet spectroscopic measurements. Binding of ER to poly(dG-m5dC).poly(dG-m5dC) increased from 15% to approx. 50-60% in the presence of 7.5 mM putrescine, 0.5 mM spermidine or 0.25 mM spermine. Maximal binding of ER to the polynucleotide was observed near the midpoint of the B-DNA to Z-DNA transition of the polynucleotide. N1-acetyl spermidine and N1-acetyl spermine facilitated the B-DNA to Z-DNA transition and the binding of ER although they were less effective than the unacetylated analog. Co(NH3)6(3+), a trivalent inorganic cation, also provoked the B-DNA to Z-DNA transition of the polynucleotide and increased its binding to ER. At higher polyamine concentrations, there was an inhibition of ER binding to the polynucleotide. In the presence of polyamines, the binding of ER to a plasmid containing ERE was 2-3-fold higher than that to a control plasmid devoid of ERE. Polyamine-induced facilitation of ER-ERE binding was also confirmed by gel mobility shift assay. Our data indicate that conformational perturbations, similar to that of the early stages of B-DNA to Z-DNA transition, are important in the recognition of ER and ERE.


Sleep and Second-Language Acquisition Revisited: The Role of Sleep Spindles and Rapid Eye Movements.
Second-language learning (SLL) depends on distinct functional-neuroanatomical systems including procedural and declarative long-term memory. Characteristic features of rapid eye movement (REM) and non-REM sleep such as rapid eye movements and sleep spindles are electrophysiological markers of cognitively complex procedural and declarative memory consolidation, respectively. In adults, grammatical learning depends at first on declarative memory ("early SLL") then shifts to procedural memory with experience ("late SLL"). However, it is unknown if the shift from declarative to procedural memory in early vs late SLL is supported by sleep. Here, we hypothesized that increases in sleep spindle characteristics would be associated with early SLL, whereas increases in REM activity (eg, density and EEG theta-band activity time-locked to rapid eye movements) would be associated with late SLL. Eight Anglophone (English first language) participants completed four polysomnographic recordings throughout an intensive 6-week French immersion course. Sleep spindle data and electroencephalographic spectral power time-locked to rapid eye movements were extracted from parietal temporal electrodes. As predicted, improvements in French proficiency were associated with changes in spindles during early SLL. Furthermore, we observed increased event-related theta power time-locked to rapid eye movements during late SLL compared with early SLL. The increases in theta power were significantly correlated with improvements in French proficiency. This supports the notion that sleep spindles are involved in early SLL when grammar depends on declarative memory, whereas cortical theta activity time-locked to rapid eye movements is involved in late SLL when grammar depends on procedural memory.


ROS-responsive capsules engineered from EGCG-Zinc networks improve therapeutic angiogenesis in mouse limb ischemia.
The successful treatment of limb ischemia requires that promote angiogenesis along with microenvironment improvement. Zinc ions have been reported to stimulate angiogenesis, but application was limited to the toxicity concerns. We hypothesized that zinc based metal-EGCG capsule (EGCG/Zn Ps) can achieve sustained release Zn2+ resulting in reduced toxicity and improve angiogenesis as well as the improvement of microenvironment by ROS scavenging of EGCG. The surface morphology, zeta potential, infrared absorbance peaks and zinc ion release profile of the EGCG/Zn Ps were measured. In vitro, EGCG/Zn showed significantly antioxidant, anti-inflammatory and induced cell migration effect. In addition, EGCG/Zn Ps enabled the sustained release of zinc ions, which reduced cytotoxicity and enhanced the secretion of vascular endothelial growth factor (VEGF) in vitro and in vivo. In mouse models of limb ischemia, EGCG/Zn Ps promoted angiogenesis and cell proliferation in ischemic tissues. Moreover, EGCG/Zn Ps group exhibited the most significant recovery of limb ischemic score, limb temperature and blood flow than other groups. In conclusion, EGCG/Zn Ps is a safe and promising approach to combine the merit of Zn2+ and EGCG, thus enabling the direct application to limb ischemia.


Levels of BNP and stress blood glucose in acute coronary syndrome patients and their relationships with the severity of coronary artery lesion.
This study aims to analyze the clinical significance of the measuring B-type natriuretic peptide (BNP) and stress glycemia in patients with acute coronary syndrome (ACS), and to investigate the relationships between the two biomarkers and the severity of coronary artery lesions. One hundred and five consecutive patients with ACS admitted for coronary artery angiography were divided into three clinical subgroups. These patients were then further assigned into either of three subgroups according to their Gensini score. Moreover, a group of patients with stable angina (SA) and those with no history of coronary disease served as controls. The patients' BNP levels were analyzed on admission and their fasting blood glucose was measured the next morning. BNP and fasting blood glucose concentrations were highly elevated in patients with ACS irrespective of their subgroups compared to SA and control patients. This observation was statistically significant (P < 0.001). Further, the concentrations of BNP and fasting blood glucose between the three ACS subgroups were significantly different (P < 0.001) depending on the severity of the coronary artery disease. There is a positive correlation between levels of BNP and blood glucose concentration and Gensini score in ACS patients (r = 0.782, P < 0.05, r = 0.732, P < 0.05). BNP level and stress glycemia were significantly higher in ACS patients than those in SA and control groups. There is a correlation between BNP level and stress blood glucose concentration and the severity of coronary artery lesions. Combined analysis of BNP and stress blood glucose can be helpful and effective for risk stratification of patients with ACS after admission.


Analytic hierarchy process as module for productivity evaluation and decision-making of the operation theater.
The analytic hierarchy process (AHP) is a theory of measurement through pairwise comparisons and relies on the judgments of experts to derive priority scales, these scales that measure intangibles in relative terms. The aim of the article was to develop a model for productivity measurement of the operation theater (OT), which could be applied as a model for quality improvement and decision-making. AHP is used in this article to evolve such a model. The steps consist of identifying the critical success factors for measuring the productivity of OT, identifying subfactors that inflauence the critical factors, comparing the pairwise, deriving their relative importance and ratings, and calculating the cumulative effect according to the attributes in OT. The cumulative productivitycan be calculated by the end and can be compared Ideal productivity to measure the productive of OT in percentage fraction. Hence, the productivity could be calculated. Hence, AHP is a very useful model to measure the productivity in OT.


Impact of severe obesity on exercise performance in heart failure with preserved ejection fraction.
Obesity plays an important role in functional impairment in HFpEF. The mechanisms underlying decreased functional capacity in obese HFpEF are not clear. We assessed the cardiac and peripheral determinants of exercise performance in HFpEF patients with class 2 obesity in the upright position, representative of posture when performing functional activities. Thirty-two HFpEF patients were divided into two groups by presence of class 2 obesity (C2, BMI ≥ 35 kg/m2 , n = 14) and non-C2 (BMI < 35 kg/m2 , n = 18). Participants performed a bout of submaximal exercise followed by incremental stages of treadmill exercise to determine peak aerobic power (peak VO2 ). Peak VO2 and Ve/VCO2 were measured using Douglas bags while cardiac output (Qc) and stroke volume (SV) were measured by acetylene rebreathing. The C2 group were younger than the non-C2 group (67 ± 6 versus 73 ± 6 years; p = .009). Comorbid condition burden was similar between groups. Peak VO2 indexed to body mass was not significantly different between groups. Absolute peak VO2 was higher in the C2 group secondary to a larger peak Qc (14.3 versus 11.0 L/min; p = .012). SV reserve was also higher in the C2 group (72 versus 49%; p = .038). HFpEF patients with severe obesity had similar cardiorespiratory fitness compared to patients with lower BMI with similar comorbidity burden. Absolute VO2 was actually higher in the severely obese driven by larger Qc and SV reserve arguing against significant effects from obesity per se on aerobic performance. The presence of a larger "cardiac engine" may offer potential for fat-loss strategies to improve impairments in functional capacity in obese patients with HFpEF.


Identification of the novel allele, HLA-DRB1*09:30, by sequence-based high resolution typing.
HLA-DRB1*09:30 shows a single nucleotide difference from DRB1*09:01:02 at nucleotide 250 (CGG→TGG).


TGFβ Signaling in Photoaging and UV-Induced Skin Cancer.
UVR is a major etiology for premature skin aging that leads to photoaging and UV-induced skin cancers. In the skin, TGFβ signaling is a growth inhibitor for keratinocytes and a profibrotic factor in the dermis. It exerts context-dependent effects on tumor progression. Chronic UV exposure likely causes TGFβ1/SMAD3 signaling activation and contributes to metalloproteinase-induced collagen degradation and photoinflammation in photoaging. UV irradiation also causes gene mutations in key elements of the TGFβ pathway, including TGFβRI, TGFβRII, SMAD2, and SMAD4. These mutations enable tumor cells to escape from TGFβ-induced growth inhibition and induce genomic instability and cancer stem cells, leading to the initiation, progression, invasion, and metastasis of cutaneous squamous cell carcinoma (cSCC). Furthermore, UV-induced mutations cause TGFβ overexpression in the tumor microenvironment (TME) of cSCC, basal cell carcinoma (BCC), and cutaneous melanoma, resulting in inflammation, angiogenesis, cancer-associated fibroblasts, and immune inhibition, supporting cancer survival, immune evasion, and metastasis. The pleiotropic effects of TGFβ provide possible treatment options for photoaging and skin cancer. Given the high UV-induced mutational burden and immune-repressive TME seen in cSCC, BCC, and cutaneous melanoma, treatment with the combination of a TGFβ signaling inhibitor and immune checkpoint blockade could reverse immune evasion to reduce tumor growth.


Incidence of community-acquired pneumonia in children caused by Mycoplasma pneumoniae: serological results of a prospective, population-based study in primary health care.
The objective of the present study was to assess the incidence of community-acquired pneumonia (CAP) in children caused by Mycoplasma pneumoniae. During 12 months in 1981-1982, all CAP cases in a defined child population were registered. M. pneumoniae aetiology, initially measured by complement fixation (CF) test, was in 1999 supplemented by measurement of IgG and IgM antibodies using enzyme immunoassays (EIA). M. pneumoniae was detected in 61 (30%) of 201 paediatric CAP cases, being the most common aetiological agent in those 5 years of age or over. At that age, M. pneumoniae was responsible for over 50% of cases, and over 90% of mycoplasmal cases were treated as outpatients. The EIA detected 17 new cases over and above the 44 detected by CF, while CF alone revealed 10 cases. The incidence of M. pneumoniae CAP increased with age, being over 10/1000 children at the age of 10 years or more. Co-infections with Streptococcus pneumoniae and Chlamydia pneumoniae were present in over 30% and 15%, respectively, of mycoplasmal CAP cases. M. pneumoniae is a common cause of paediatric CAP in primary health care, and co-infections with S. pneumoniae are common. Both S. pneumoniae and M. pneumoniae should be taken into account when starting antibiotics for children with CAP.


Morning admission for a same-day surgical procedure: resolution of a blood bank problem.
To minimize the risks associated with an elective surgical procedure on the day of admission without adequate time for blood bank serologic analysis, we implemented two administrative changes: (1) collection of blood samples from patients on the evening before operation and (2) a system for recommending a 3-hour delay of the operation in those cases without such a sample. During a 4-month period before implementation of these changes, 70 patients had serologic problems; morning blood samples had been obtained from 36 of these patients. For a comparable time after implementation of these changes, a serologic problem was encountered in 41 surgical cases, in 7 of which morning blood samples had been obtained. Similarly, the number of cases in which the operation was begun before resolution of a serologic problem decreased from 19 to 3. These decreases occurred despite a 13.4% increase in total morning-admission cases between the first and second study periods. Although no patient experienced adverse transfusion-related events during either study period, simple administrative changes that necessitated no increases in costs were instrumental in substantially decreasing the risks to patients.


Niacin modulates depressive-like behavior in experimental colitis through GPR109A-dependent mechanisms.
Depression is one of the common neurological comorbidities in patients with inflammatory bowel disease (IBD). The current study aimed to investigate the potential impact of niacin on colitis-induced depressive-like behavior in rats. Animals were given 5 % dextran sulfate sodium (DSS) in drinking water for one week to induce colitis. Niacin (80 mg/kg), with or without mepenzolate bromide (GPR109A blocker), was administered once per day throughout the experimental period. Rats were tested for behavioral changes using open field and forced swimming tests. Niacin significantly ameliorated DSS-induced behavioral deficits and alleviated macroscopic and microscopic colonic inflammatory changes. It also augmented the hippocampal levels of ZO-1, occludin, and claudin-5 proteins, indicating the ability of niacin to restore the blood-brain barrier (BBB) integrity. Moreover, niacin decreased hippocampal IL-1ꞵ and NF-ĸB contents but increased GSH, Sirt-1, Nrf-2, HO-1 concentrations. All these beneficial effects were partially abolished by the co-administration of mepenzolate bromide. The neuroprotective effect of niacin against DSS-induced depressive-like behavior was partially mediated through GPR109A-mediated mechanisms. Such mechanisms are also involved in modulating neuronal oxidative stress and inflammation via Sirt-1/Nrf-2/HO-1 signaling pathways.


Langerhans cells in human lung tumours: an immunohistological study.
In an immunocytochemical study of 41 human lung tumours we have shown that Langerhans cells can be reliably identified using the anti-CD1 monoclonal antibody NA1/34. Langerhans cells are present in all the main varieties of human lung tumour although they are infrequent in both small cell carcinoma and carcinoid tumour. There is considerable variation in numbers of Langerhans cells in both adenocarcinomas and squamous cell carcinomas. In this study tumours were divided into those with high numbers of Langerhans cells (greater than 2 per high power field) and those with low numbers (less than 2 per high power field). Analysing these results against patient survival showed a markedly worse survival in those tumours with a high number of Langerhans cells for all the tumours as a single group and for squamous cell carcinoma as a single entity.


Predictive value of selected sperm parameters for classical in vitro fertilization procedure of oocyte fertilization.
A proportion of fertilized oocytes during classical in vitro fertilization (IVF) procedure was analysed depending on the following factors: number of mature oocytes, seminological criteria such as sperm morphology in raw semen and after its selection in a density gradient (six structural defects of a male gamete were taken into consideration), sperm concentration, motility parameters according to World Health Organization criteria and the functional tests: hypo-osmotic swelling assay and acrosomal reaction induced by calcium ionophore. Evaluation of DNA content in sperm by image cytometry and determination of malonyldialdehydes in seminal plasma were also performed. Seventy-nine semen samples from patients undergoing IVF were assessed. Apart from significant correlations obtained for selected semen parameters and proportion of fertilized eggs, logistic regression analysis showed that the best predictive factors for oocyte fertilization were normal morphology of sperm before and after gradient selection, grade B and C of sperm movement in raw semen, and DNA content after density gradient centrifugation, which all accounted for 76.7% of fertilization predictive value.


Screening for breast cancer among young Jordanian women: ambiguity and apprehension.
The goal of this study was to understand young Jordanian women's attitudes towards breast cancer screening practices in order to improve young women's uptake of screening and early detection. The incidence of breast cancer is increasing annually among younger Jordanian women; however, little is known about their attitudes towards breast cancer and associated screening practices. Young women's attitudes towards breast cancer must be taken into account when designing screening strategies and interventions specifically for this age group. Screening strategies must also acknowledge young women's cultural context; however, little is known about how culture shapes their understandings and practices. A qualitative interpretive approach was utilized to interview 45 young educated women about their breast cancer views and screening practices. Data were analysed thematically. Four overlapping themes emerged: (i) young women should not think about it, (ii) absence of a role model, (iii) cultural shame of breast cancer, and (iv) cancer means death and disability. The study found high levels of apprehension and ambiguity related to breast cancer. This was associated with the perceived impact of a cancer diagnosis on a young woman's social status and family role. Family support was perceived to be a necessary prerequisite for seeking treatment or screening. Understanding young women's perception about screening and early detection of breast cancer is essential for policy makers and healthcare providers to design culturally appropriate and age-appropriate health promotion campaigns and services.


[Radiologic determination of the length of the distal end of the radius and ulna].
The influence of inaccurate positioning of the hand and forearm upon the relative lengths of the ulna and radius is investigated systematically in anatomical specimens and living persons. Increased or decreased ulnar lengths could be produced by moving up and down, by tilting or by pronation of the forearm. Extension of the elbow also influences the ulnar variance measurement.


Abundance, distribution and composition of microplastics in sediment and fish species from an Urban River of Bangladesh.
Microplastics (MPs) are a growing concern due to its ubiquitous presence and exceptional stability. We examined the abundance, dispersion, and attributes of MPs in the sediment and fish species of the Turag River in Bangladesh, which separated the industrial city Gazipur from the Mega-city Dhaka. Collected samples were digested and the chemical structure was identified using ATR-FTIR spectroscopy. The concentration of MPs in the sediment ranged from 10 to 35 particles kg-1, with a mean abundance of 19.2 ± 2.44 particles kg-1and MPs of the fragment type account for 34 % of all. The majority of MPs were discovered in the 3-5 mm size range. MPs concentrations in freshwater fish gut from the Turag River ranged from 0.63 ± 0.18 to 7.0 ± 1.1 microplastics individual-1. Fiber was found to be the most commonly ingested MPs type (43 %), followed by fragments (41 %), film (12 %), and foam (4 %). The most common type of MPs was transparent (34 %) followed by red (28 %), white (20 %), green (9 %) and black (8 %). The results showed that demersal (1.87 ± 0.39 items individual-1) and benthopelagic (1.5 ± 0.26 items individual-1) fish species had more MPs than pelagic fish (0.63 ± 0.18 items individual-1) species. Polypropylene (PP) was found to be the most dominant polymer type in the sediment sample, and PS (39 %) in the fish sample. Polyethylene (PE) was discovered to be 30 % and PP 25 % in sediment and fish samples, respectively. Other commonly detected polymer types include polyamide (PA), polystyrene (PS), cellulose acetate (CA), and polyethylene terephthalate (PET). In different sampling sites along the Turag River, the pollution load index (PLI) of MPs contamination was found to be in the risk level category I. The PLI values reflected the city's anthropogenic influence. The findings of the study could be used to establish a baseline for MPs pollution in Bangladesh's vast freshwater ecosystem.


Lack of homozygously inactivated p73 in single-copy MYCN primary neuroblastomas and neuroblastoma cell lines.
We examined 18 neuroblastoma cell lines and 32 primary single-copy MYCN tumor specimens to determine whether mutations of p73, a novel p53-related gene located in chromosome band 1p36.33, contribute to the genesis or progression of childhood neuroblastoma. By fluorescence in situ hybridization, 16 of the 18 cell lines, but only 3 of the 32 primary tumors, had evidence of a deleted p73 allele. Sequence analysis of the p73 coding region in the mRNAs expressed by these cell lines and tumors did not reveal inactivating mutations, suggesting that p73 is not homozygously inactivated in neuroblastoma. However, several novel splice forms of p73 mRNAs were identified, including one without exon 11 that predominated in multiple MYCN-amplified cell lines. Its encoded p73 protein differed from other splice forms in that the C-terminus was derived from an alternative reading frame. Further study of the functional properties of the protein encoded by this splice form of p73 will be needed to determine whether it contributes to the pathogenesis of childhood neuroblastoma with MYCN gene amplification.


Postnatal Management of Myelomeningocele: Outcome with a Multidisciplinary Team Experience.
Myelomeningocele (MMC) is a complex neural tube defect. Few studies report the results of modern postnatal management. The goal of this study was to report the long-term outcome of a multidisciplinary approach of patients with MMC. Forty-six MMCs were included. Clinical status was evaluated prospectively. Mean follow-up was 8.1 years. The level of the malformation was sacral or lower lumbar (≤L4) in 27 cases, higher lumbar (between L1 and L3) in 5 cases, and thoracic in 14 cases. A Chiari II malformation was present at birth in 78.3% of the cases. Seventy-six percent of the patients were operated on within the first 24 hours of life. Sixty-one percent needed a cerebrospinal fluid diversion procedure. Seven patients underwent a second surgery for a retethering of the spine. Eighty percent presented with orthopedic problems. Sixty-five percent of our patients were able to walk. Only 13% of patients had a normal urinary elimination. Two groups of patients were identified: one group with a malformation at the level of L4 or below (group 1) and another group with a malformation strictly above L4 (group 2). Group 1 had significantly better outcome. This series proves that modern multidisciplinary postnatal management of MMC is effective. In the light of these results and of the results of prenatal management of MMC, prenatal surgery seems to be a highly valuable tool to improve the outcome of patients with high lesions (level ≥L3).


Medium term fate of cartilage grafts from children after laryngo-tracheoplasty.
Cartilage grafts or biopsies of such grafts were obtained from six children who had undergone laryngo-tracheoplasty surgery at times ranging from 10 to 38 months after surgery. The histological appearance of the grafted cartilage was of gradual degeneration with chondrocyte necrosis and replacement of cartilage matrix by fibrous tissue.


Evaluation of a novel doppler index of combined systolic and diastolic myocardial performance in Newfoundland dogs with familial prevalence of dilated cardiomyopathy.
A Doppler index of myocardial performance (IMP) has been recently proposed in human cardiology, which is calculated from the isovolumic contraction time (ICT), isovolumic relaxation time (IRT), and the ejection time (ET) using the following formula: (ICT+IRT)/ET. In this study, IMP was measured and evaluated in Newfoundland dogs categorized in four groups: Normal dogs (n = 31), dilated cardiomyopathy (DCM) (n = 34), depressed fractional shortening (dFS) (n = 27), and left ventricular enlargement (LVE) (n = 7). IMP was found to be independent of age, sex, body surface area, and the R-R interval in the Normal group. There were significant differences in IMP between the DCM group and the Normal and dFS groups (P < 0.05) and between Newfoundlands with overt vs. occult DCM. IMP is a Doppler index which appears to correlate with severity of disease and may be of use in the early diagnosis of affected dogs during screening for the presence of DCM.


Repeatability of anorectal manometry in healthy volunteers and patients.
Anorectal manometry is used extensively in the assessment of patients with disorders of the pelvic floor. The present study investigated the repeatability of anorectal manometry in healthy volunteers and patients. A total of 30 healthy volunteers (15 men and 15 women) and 10 patients with fecal incontinence (4 men and 6 women) underwent perfusion manometry and volumetry. Intraindividual variability was evaluated using the intraindividual correlation coefficient (ICC). Interindividual variability was expressed as the standard deviation from the calculated mean values. We found a high intraindividual correlation for the squeezing pressure (ICC 0.75-0.95), vector volume (ICC 0.88-0.97), and rectal perception (ICC 0.82-0.98). The anal resting pressure showed moderate repeatability (ICC 0.60-0.72). However, with regard to sphincter asymmetry, rectal compliance, and the rectoanal inhibitory reflex, a wide range of variability was found. In the female volunteers, the squeezing pressure and vector volume were lower than in those in the male volunteers. The anal pressure, vector volume, thresholds for urgency, and the maximum tolerable volume were lower in the incontinent patients than in the healthy volunteers. The squeezing pressure, vector volume, and rectal perception allow a reliable analysis of anal sphincter function. Sphincter asymmetry, rectal compliance, and the rectoanal inhibitory reflex were of limited diagnostic value.


Rectal Foreign Body Removal in the Emergency Department: A Case Report.
Rectal foreign bodies (RFB) pose a challenge to emergency physicians. Patients are not often forthcoming, which can lead to delays to intervention. Thus, RFBs require a heightened clinical suspicion. In the emergency department (ED), extraction may require creative methods to prevent need for surgical intervention. The authors present a case of a successful extraction of a RFB in the ED and review of the literature. Retained RFBs are an unusually problematic reason for an ED visit. Thus, it is important for emergency physicians to be comfortable managing such cases appropriately.


Cell line OCI/AML3 bears exon-12 NPM gene mutation-A and cytoplasmic expression of nucleophosmin.
We recently identified a new acute myeloid leukemia (AML) subtype characterized by mutations at exon-12 of the nucleophosmin (NPM) gene and aberrant cytoplasmic expression of NPM protein (NPMc+). NPMc+ AML accounts for about 35% of adult AML and it is associated with normal karyotype, wide morphological spectrum, CD34-negativity, high frequency of FLT3-ITD mutations and good response to induction therapy. In an attempt to identify a human cell line to serve as a model for the in vitro study of NPMc+ AML, we screened 79 myeloid cell lines for mutations at exon-12 of NPM. One of these cell lines, OCI/AML3, showed a TCTG duplication at exon-12 of NPM. This mutation corresponds to the type A, the NPM mutation most frequently observed in primary NPMc+ AML. OCI/AML3 cells also displayed typical phenotypic features of NPMc+ AML, that is, expression of macrophage markers and lack of CD34, and the immunocytochemical hallmark of this leukemia subtype, that is, the aberrant cytoplasmic expression of NPM. The OCI/AML3 cell line easily engrafts in NOD/SCID mice and maintains in the animals the typical features of NPMc+ AML, such as the NPM cytoplasmic expression. For all these reasons, the OCI/AML3 cell line represents a remarkable tool for biomolecular studies of NPMc+ AML.


Outcome of Treatment of Uveitic Macular Edema: The Multicenter Uveitis Steroid Treatment Trial 2-Year Results.
To evaluate the 2-year outcomes of uveitic macular edema. Longitudinal follow-up of a randomized cohort. At baseline, 148 eyes of 117 patients enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial had macular edema, and 134 eyes of 108 patients completed 2-year follow-up. Patients enrolled in the study were randomized to either systemic immunosuppression or intravitreal fluocinolone acetonide implant therapy. Macular edema was defined as thickening of the retina (center point thickness≥240 μm) on time-domain optical coherence tomography (OCT) of macula. Improvement in macular edema (≥20% reduction in central point thickness on OCT), resolution of macular edema (normalization of thickness on OCT), and best-corrected visual acuity (BCVA). Between randomization and 2-years' follow-up, 62% and 25% of eyes in the systemic and implant groups, respectively, received at least 1 supplemental regional corticosteroid injection. By 2-years' follow-up, macular edema improved in 71% of eyes and resolved in 60%. There were no differences between treatment groups in the proportion of eyes with macular edema improving (systemic therapy vs. implant, 65% vs. 77%; P=0.20) and resolving (52% vs. 68%; P=0.28), but eyes randomized to implant had more improvement in macular thickness (median decrease of 180 vs. 109 μm in the systemic therapy group; P=0.04). Eyes with baseline fluorescein angiographic leakage were more likely to improve than those without (76% vs. 58%; P=0.03). Overall, there was a mean 5-letter (1 line) improvement in BCVA at 2 years. Mean changes in BCVA from baseline at 2 years by macular edema response status were: resolution, +10 letters; improvement without resolution, +10 letters (P=0.92); little to no change, 6 letters (P=0.19); and worsening, -16 letters (worsening acuity; P=0.0003). About two thirds of eyes with uveitic macular edema were observed to experience improvement in the edema and visual acuity with implant or systemic treatment. Fluocinolone acetonide implant therapy was associated with a greater quantitative improvement in thickness. Fluorescein angiography leakage was associated with a greater likelihood of improvement in macular edema.


Preclinical study for the ameliorating effect of l-ascorbic acid for the oxidative stress of chronic administration of organic nitrates on myocardial tissue in high sucrose/fat rat model.
The therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. Hemoglobin tightly binds to NO forming methemoglobin altering the erythrocytic antioxidant defense system. The principal objective of our research is to show the ameliorating effect of l-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs used in cardiovascular diseases such as oxidative stresses and tolerance. We studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered different concentrations of Isosorbide-5-mononitrate (ISMN) 0.3 mg/kg, 0.6 mg/kg and 1.2 mg/kg. Afterwards, we evaluated the role of l-ascorbic acid against these biochemical changes in cardiac tissues. Chronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of the pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in the myocardium muscles in a dose-dependent manner. Meanwhile, such exposure caused a decline in the enzymatic effect of SOD, GSH and CAT accompanied by a decrease in the level of mitochondrial oxidative stress marker (nrf2) in the myocardium muscles and a decrease in the serum iron and total iron-binding capacity (TIBC) in a dose-dependent manner. Concomitant treatment with l-ascorbic acid significantly diminished these changes for all examined parameters. Chronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to the generation of reactive oxygen species. Using l-ascorbic acid can effectively ameliorate such intoxication to overcome nitrate tolerance.


Evaluation of a smartphone-based rapid fluorescent diagnostic system for H9N2 virus in specific-pathogen-free chickens.
Repeated interspecies transmission of H9N2 virus from poultry to humans and human infections transmitted via aerosols highlight the need for a highly sensitive, rapid diagnostic system for the detection of this virus. However, no such test exhibiting high performance has been developed. In this study, the performance of a smartphone-based rapid fluorescent diagnostic system (SRFDS) was optimized for the diagnosis of an H9N2-virus-infected animal. To suppress the nonspecific reactivity of the bioconjugate in oropharyngeal (OP) and cloacal (CL) samples derived from chickens, different blocking reagents were tested, and a mixture of casein and sucrose was found to be optimal. To assess the performance of SRFDS, OP and CL samples were obtained from specific-pathogen-free chickens and used for comparison of this method with real-time reverse transcription PCR (rRT-PCR) at time points of three, five, and seven days postinfection (dpi). The limit of detection of SRFDS was found to be 7.5 PFU/mL, which was 138-fold higher than that of a conventional colloidal-gold-based avian influenza rapid diagnostic test. In the animal study, the presence of viral antigen was monitored with SRFDS, and the relative sensitivity (relative to rRT-PCR results) was 94.44 % (17/18) and 95.23 % (20/21) in OP and CL specimens, respectively. The specificity of SRFDS was 100 %. These results imply that the diagnostic performance of SRFDS might be comparable to that of rRT-PCR for diagnosis of H9N2 in chickens and that this test can be used as a highly sensitive rapid diagnostic method in field studies on broiler poultry and wild birds.


Morphologic characteristics of pancreatic carcinoma with diabetes mellitus.
For 81 cases of resectable pancreatic carcinoma, the site of cancer origin, cancer histologic features, and hyperplasia in the noninvolved duct were studied in relation to diabetes. They were classified into the following three groups: (1) fasting blood sugar (FBS) of less than 120 mg/dl (Group A, 26 cases); (2) FBS of more than 120 mg/dl with less than 2-year history of diabetes (Group B, 38 cases); and (3) FBS of more than 120 mg/dl with more than a 2-year history of diabetes (Group C, 17 cases). Although neither tumor size nor tumor location differed between the three groups, both the highest resectability (47%) and the lowest rate (71%) of extrapancreatic invasion were seen in Group C. A pancreatic ductogram showed that the pattern of the main pancreatic duct was intact in 0% in Group C versus 35% in Group A (P less than 0.05). Histologically, papillary/well-differentiated adenocarcinoma was present in 35% of Group A patients versus 61% of Group B and 71% of Group C patients (P less than 0.05). Papillary hyperplasia was present in the ducts of 27% of the patients in Group A; this was significantly lower than the other two groups. Atypical duct hyperplasia was present in 47% of Group C patients; this was significantly higher than in the other two groups. It appears that cells in the main pancreatic duct are vulnerable to hyperplastic and well-differentiated cancerous changes in patients with a history of diabetes of more than 2 years duration.


Legionella associated rhabdomyolysis: a case report.
Infections have been recognized as an uncommon cause of rhabdomyolysis, with evidence indicating a worse prognosis when compared to rhabdomyolysis caused by other etiologies. Diseases caused by Legionella pneumophila can present variably, ranging from mild to severe illness, as is sometimes the case with pneumonia. In particular, the triad of Legionnaire's disease, rhabdomyolysis, and acute kidney injury is associated with a significant increase in the morbidity and mortality, with most patients requiring initiation of renal replacement therapy such as hemodialysis. While the exact mechanism of both the muscle and kidney injury in this setting remains unknown, several hypotheses exist, with some research suggesting multiple yet distinct processes occurring in both target organs. In this case report, we describe a 53-year-old African American man who presented with Legionella pneumophila pneumonia complicated by rhabdomyolysis and acute kidney injury. He was treated with aggressive fluid resuscitation and a 2-week course of azithromycin. His clinical status improved without necessitating renal replacement therapy or mechanical ventilation. We postulate that early recognition and treatment were key to his recovery. He was discharged 10 days later without recurrence of rhabdomyolysis at the time of this report. While there are several well-established and more common causes of rhabdomyolysis, clinicians should recognize Legionella sp. as an etiology, given its association with significant morbidity and mortality.


Functional recognition of a distinct receptor preferential for leukotriene E4 in mice lacking the cysteinyl leukotriene 1 and 2 receptors.
The cysteinyl leukotrienes (cys-LTs) are a family of potent lipid mediators of inflammation derived from arachidonic acid. Activation of certain cell types results in the biosynthesis and export of leukotriene (LT) C(4), which then undergoes extracellular metabolism to LTD(4) and LTE(4). LTE(4), the most stable cys-LT, is only a weak agonist for the defined type 1 and type 2 cys-LT receptors (CysLT(1)R and CysLT(2)R, respectively). We had recognized a greater potency for LTE(4) than LTC(4) or LTD(4) in constricting guinea pig trachea in vitro and comparable activity in eliciting a cutaneous wheal and flare response in humans. Thus, we hypothesized that a vascular permeability response to LTE(4) in mice lacking both the CysLT(1)R and CysLT(2)R could establish the existence of a separate LTE(4) receptor. We now report that the intradermal injection of LTE(4) into the ear of mice deficient in both CysLT(1)R and CysLT(2)R elicits a vascular leak that exceeds the response to intradermal injection of LTC(4) or LTD(4), and that this response is inhibited by pretreatment of the mice with pertussis toxin or a Rho kinase inhibitor. LTE(4) is approximately 64-fold more potent in the CysLT(1)R/CysLT(2)R double-deficient mice than in sufficient mice. The administration of a CysLT(1)R antagonist augmented the permeability response of the CysLT(1)R/CysLT(2)R double-deficient mice to LTC(4), LTD(4), and LTE(4). Our findings establish the existence of a third receptor, CysLT(E)R, that responds preferentially to LTE(4), the most abundant cys-LT in biologic fluids, and thus reveal a new target for therapeutic intervention.


γ-Tubulin 2 nucleates microtubules and is downregulated in mouse early embryogenesis.
γ-Tubulin is the key protein for microtubule nucleation. Duplication of the γ-tubulin gene occurred several times during evolution, and in mammals γ-tubulin genes encode proteins which share ∼97% sequence identity. Previous analysis of Tubg1 and Tubg2 knock-out mice has suggested that γ-tubulins are not functionally equivalent. Tubg1 knock-out mice died at the blastocyst stage, whereas Tubg2 knock-out mice developed normally and were fertile. It was proposed that γ-tubulin 1 represents ubiquitous γ-tubulin, while γ-tubulin 2 may have some specific functions and cannot substitute for γ-tubulin 1 deficiency in blastocysts. The molecular basis of the suggested functional difference between γ-tubulins remains unknown. Here we show that exogenous γ-tubulin 2 is targeted to centrosomes and interacts with γ-tubulin complex proteins 2 and 4. Depletion of γ-tubulin 1 by RNAi in U2OS cells causes impaired microtubule nucleation and metaphase arrest. Wild-type phenotype in γ-tubulin 1-depleted cells is restored by expression of exogenous mouse or human γ-tubulin 2. Further, we show at both mRNA and protein levels using RT-qPCR and 2D-PAGE, respectively, that in contrast to Tubg1, the Tubg2 expression is dramatically reduced in mouse blastocysts. This indicates that γ-tubulin 2 cannot rescue γ-tubulin 1 deficiency in knock-out blastocysts, owing to its very low amount. The combined data suggest that γ-tubulin 2 is able to nucleate microtubules and substitute for γ-tubulin 1. We propose that mammalian γ-tubulins are functionally redundant with respect to the nucleation activity.


Congenital sialoblastoma (embryoma) associated with premature centromere division and high level of alpha-fetoprotein.
Sialoblastoma is a rare, locally aggressive, and potentially malignant perinatal salivary tumor that predominantly affects the parotid glands. To date, 29 cases of sialoblastoma have been reported. We report a further case of sialoblastoma diagnosed at 37 weeks of gestation presenting with novel findings that are the premature centromere division and a high level of alpha-fetoprotein.


Reduction of body fat stores by inhibition of prolactin secretion.
Reductions of prolactin secretion by bromocriptine treatment for 24 days reduced fat stores (abdominal and epididymal fat depots) in hamsters by 25-49% compared with control animals. However, body weights and food consumption were not affected. These results further substantiate an important role for prolactin in regulation of fat metabolism and indicate that bromocriptine might be used to decrease fat stores.


Characterization of the ATP-phosphohydrolase activity of bovine spermatozoa flagellar extracts.
The ATP-phosphohydrolase activity of extracts prepared from bovine spermatozoa flagella (BSFE), was characterized with respect to enzyme, substrate, activator ion and salt concentration, temperature dependence and time stability. BSFE required the presence of a divalent cation for activity: Mg++ or Ca++ could function as activator; Mn++, Zn++ and Cd++ could not. EDTA, but not EGTA, was inhibitory to enzymatic activity. Ca++ inhibited the Mg++ stimulated activity. ATP was dephosphorylated more rapidly than GTP greater than CTP greater than ITP, and ADP was dephosphorylated at 40% of the rate of ATP. The magnesium activated ATPase was stimulated by potassium and inhibited by sodium ions. Activation of BSFE ATP-phosphohydrolase was maximal in the presence of Mg++ and ATP in equimolar concentrations and K+ (0.05-0.3 M) at 30 degrees C. Although the enzymatic activity of the extract was found to decrease rapidly with time, it could be maintained for up to three days by the addition of 2-beta-mercaptoethanol to the bovine spermatozoa flagellar extracts.


In vitro immune responses to PPD, extracts from Raji cells and nasopharyngeal carcinoma biopsies in NPC leucocytes.
Peripheral leucocytes from nasopharyngeal carcinoma (NPC) patients and control subjects, which included healthy subjects and patients with other cancers, have been tested against PPD and a panel of extracts from Raji cells and pooled NPC biopsies, using the blast transformation and the macrophage migration inhibition assays. The results of both assays indicated that the in vitro cell-mediated immune (CMI) responses to the Raji-cell extracts and NPC-biopsy extracts were associated with NPC. However, the peripheral leucocytes from NPC patients and control subjects responded similarly to PPD. These results are in general accord with the skin tests reported by Levine et al. (1976) and Ho, Ng and Kwan (1977b). The antigenic specificity of the NPC-associated CMI responses remains, however, to be resolved, as the extracts used in these or in the in vivo CMI studies were heterogeneous mixtures.


Clinical experience of infective endocarditis complicated by acute cerebrovascular accidents.
To evaluate the clinical results of patients with infective endocarditis (IE) complicated by acute cerebrovascular accidents (CVAs). A total of 44 patients with IE complicated by CVA at admission were retrospectively analyzed in a single medical institute from 2005 to 2011. At the time of admission, 18 patients were diagnosed with hemorrhagic stroke, and 26 patients were diagnosed with ischemic stroke. Fifteen patients received surgical intervention during hospitalization. The hospital mortality rate was 38.9% for the hemorrhagic stroke group and 42.3% for the ischemic stroke group (p = 0.821). The mortality rate was 33.3% for the surgical group and 44.8% for the nonsurgical group (p = 0.531). At 30 days of hospitalization, 45.8% of the patients experienced an adverse event (defined as death due to organ failure, restroke, cardiogenic shock, or septic shock during the treatment period), and the attrition rate was 1.5% per day. Surgery performed after the adverse events increased mortality (80.0%) compared with surgery performed on patients with no adverse events (10.0%; p = 0.017). A Cox regression analysis revealed that creatinine > 2 mg/dL, diabetes, and staphylococcal infection were the risk factors of the adverse events. Early surgical intervention for IE with ischemic stroke may prevent adverse events, particularly in patients with impaired renal function, diabetes, or staphylococcal infection. A delay in operation of > 30 days is recommended after hemorrhagic stroke.


Delayed hemorrhage from an anomalous carotid artery following tracheostomy.
A report is presented in which a patient's unusual aortic arch anomaly ruptured following tracheostomy. Appreciation of the high incidence of such anomalies may prepare the physician to avoid injury during tracheostomy or successfully manage late hemorrhage when it occurs.


Undocumented pregnant women: what does the literature tell us?
The present literature review was conducted to determine what information has been published on the topic of undocumented pregnant migrants. Scientific databases and gray literature sources were searched for articles published between January 1967 and September 2010. Eighty-seven articles met the inclusion criteria and were reviewed. A final sample of 23 articles was included in the review. Existing evidence suggests that pregnant undocumented migrants living in Western societies tend to be younger, unmarried, and more likely to be employed in the domestic sector than documented migrants and permanent residents. They have less access to prenatal care and consult later in pregnancy than controls. Findings concerning delivery and birth outcomes are conflicting and subject to several biases. Little has been published on programs to address the needs of undocumented pregnant women living in Western countries. More research on the particular health and social issues faced by these women is needed.


Do calcium supplements increase serum and urine calcium levels in post-menopausal women?
The frequent prescription of calcium supplements with vitamin D by health practitioners is a topic of concern globally. The present study was designed to find out whether the calcium supplements with vitamin D really affect serum and urinary calcium levels in post-menopausal women. The age-matched comparative study was performed among postmenopausal women who were already on and those who were not on calcium supplements with vitamin D for a period of time in relation to the estimation of the serum calcium and the urine calcium levels. Sixty healthy postmenopausal women were enrolled, with thirty among them forming the study group (SG) - who were on calcium supplements with vitamin D for a period of a month, three months, and up to twelve months - were studied and compared the results obtained with the age-matched control group (CG) of thirty post-menopausal women who were not on calcium supplements. The serum and the urinary calcium levels were estimated by using appropriate biochemical methods and the data were analysed using relevant statistical methods. The serum calcium levels did not vary significantly in SG in spite of consuming calcium supplements over a period of time, whereas the urinary calcium levels increased progressively (p value < 0.005) in those who have taken calcium supplements for a year compared to those who have taken for a month. Thus, the calcium supplements were of little significance on the serum calcium levels, but have a significant effect on the urinary calcium levels in post-menopausal women.


ROPA - Lesbian shared in vitro fertilization - Ethical aspects.
Recently, a technique of assisted reproduction was developed to allow lesbian women to share biological motherhood of their offspring - the ROPA method (in Spanish - Recepción de Ovocitos de Pareja; in English - Reception of Partner's Oocytes), also known as lesbian shared in vitro fertilization. One mother provides the oocytes (genetic mother) and the other receives the embryo and gets pregnant (gestational mother). As for most issues related to medically assisted reproduction, this technique raises a lot of ethical questions in respect to patients, future offspring, gametes, and embryos. Furthermore, the fact that it is directed to homosexual women poses its own issues, both biological and social in nature. This is a state-of-the-art review of the main ethical dilemmas related to this technique, primarily focusing on the basic principles of bioethics, but also specific concerns directly related to this kind of treatments.


Tragal cartilage augmentation in repair of cleft palate, a new technique and its clinical implications.
Cleft palate is one of the most common congenital anomalies of the head and neck worldwide. In addition to the evident feeding and growth problems, patients are involved with and suffer from speech, hearing and dental problems. Many surgical techniques and modifications have been advocated to improve functional outcome and aesthetic results, aiming at normal speech, minimizing growth disturbances, and establishing a competent velopharyngeal sphincter. Despite the variety of techniques described for repair of the clefts, there is still a relatively high incidence of postoperative fistula reaching up to 35%. This is mainly related to type and degree of the defect, and type of surgical repair. To evaluate the efficacy of placement of tragal cartilage free graft between the oral and nasal mucosal layers of the neo-palate in improving success rates, and anatomical and functional outcomes in repair of cleft palate with reduction of the extent of dissection. Fourteen patients were managed by our technique, only in large cases minimal von Langenbeck lateral release incisions were made. In all cases a tragal cartilage graft was interpositioned and fixed to the muscle layer of the neo-palate, 2-3 extramucosal trans-muscle sutures were placed for 3-4 weeks if needed, and the patients were followed up for a minimum of 12 months during which functional and anatomical assessments were done. Results, including both anatomical and functional outcomes, were favorable with no gross failures, permanent significant fistula formations (one case with minor non-significant fistula), nor donor site co morbidities. The use of tragal cartilage free graft to augment the area at the junction between the hard and soft palate appears to be a safe and effective method in repair of cleft palate that reduces the incidence of postoperative palatal fistulae, without donor site comorbidities.


Expression of transgenes in primary neurons from chick peripheral and central nervous systems by retroviral infection of early embryos.
Many cell biological studies require the expression of transgenes in cells in culture, but it is difficult to obtain uniform, stable, and efficient expression of transgenes in primary neurons. We have approached this problem by adapting from developmental biologists the avian retroviral vector, RCAS. This vector allows the introduction of a transgene by infection early in chick embryonic development. Transgenes that are less than 2.6 kb in size can be cloned through an adapter vector, SLAX 12 NCO, and into the RCAS retroviral vector with relative ease. The vector is then used to produce active virus, and the virus is injected into the neural tube or ventricles of stage 10 embryos. By infecting the neuronal precursor cells while they are still mitotic, the retrovirus and accompanying transgene are introduced into the genome and subsequently spread by replication, shedding of new virus, and infection of other cells. Embryos are incubated from the time of injection until E9-E12 and peripheral and central nervous system neurons are dissected out and grown in culture using standard techniques. In this manner, the majority of the sympathetic and dorsal root ganglion neurons can be induced to express the trangene. A similar result, at lower efficiencies, is obtained for central nervous system neurons.


Correction: In situ monitoring of functional activity of extracellular matrix stiffness-dependent multidrug resistance protein 1 using scanning electrochemical microscopy.
[This corrects the article DOI: 10.1039/D2SC02708A.].


Coping strategies, illness perception, anxiety and depression of patients with idiopathic constipation: a population-based study.
Functional constipation has important psychological elements. To investigate the prevalence of functional constipation in an Asian population, and the interplay among functional constipation, anxiety/depression, perception and coping strategies. An interview of 3282 patients was made by telephone survey. Constipation was diagnosed by Rome II criteria. Coping ability and anxiety/depression were assessed by validated questionnaires. Fourteen percent of the interviewees had constipation. Anxiety and depression scores were higher in constipated than in healthy subjects (P < 0.0001 and < 0.0001), and in female than male patients (P = 0.02 and < 0.0001). Patients who were aware of their symptoms perceived greater impact on their lives (P < 0.001). Frequent use of coping strategies associated with lower anxiety scores (P < 0.0001). Female were more frequently aware of the symptoms (P = 0.004), less frequently used coping strategies (P = 0.008). Regression analysis showed that female and high anxiety level were the independent factors for predicting the perception of constipation, whereas anxiety was the only independent factor for predicting the use of coping strategies. Constipation associated with anxiety and depression is prevalent in the general Asian population. Female sex and anxiety are important aetiological factors in constipation, affecting perception and the use of coping strategies.


Regional Anesthesia for Vascular Surgery and Pain Management.
Patients undergoing vascular surgery tend to have significant systemic comorbidities. Vascular surgery itself is also associated with greater cardiac morbidity and overall mortality than other types of noncardiac surgery. Regional anesthesia is amenable as the primary anesthetic technique for vascular surgery or as an adjunct to general anesthesia. When used as the primary anesthetic, regional anesthesia techniques avoid complications associated with general anesthesia in this challenging patient population. In this article, the authors describe regional anesthetic techniques for carotid endarterectomy, arteriovenous fistula creation, lower extremity bypass surgery, and amputation.


Comparison of intracellular PO2 and conditions for blood-tissue O2 transport in heart and working red skeletal muscle.
1. Neither anoxic nor hypoxic cells were found in epicardium of anaesthetized dogs, cats, rabbits and rats despite heterogeneity of flow (Wieringa et al., 1982) and haematocrit (Honig et al., in press) in the coronary capillary network. 2. Median PO2 in unstressed dog heart and cat heart are 4.8 and 5.2 torr, respectively. These values are close to the P50 of the oxymyoglobin dissociation curve, and well above PcritO2. 3. A dense, interconnected capillary network and high capillary haematocrit appear essential to achieve high O2 extraction at flows characteristic of maximally working myocardium. 4. Mb promotes O2 transport in myocardium by: a) maximizing the driving force for transcapillary diffusion, b) minimizing spatial variability in PmbO2, c) facilitating O2 diffusion in myocytes and, d) permitting close capillary packing without a diffusion shunt for O2. 5. The O2 conductance of the red cell-capillary system is a major determinant of O2 mass transfer in red muscle.


Lead-induced cardiomyocytes apoptosis by inhibiting gap junction intercellular communication via autophagy activation.
Lead (Pb) is one of the most common heavy metal contaminants in the environment. Pb can cause pathophysiological changes in several organ systems, including the cardiovascular system, but the molecular mechanism remains elusive. The study aimed to study the effects of Pb on Gap junction intercellular communication (GJIC) and its role in Pb-induced apoptosis. The present study aims to determine whether Pb-induced autophagy promotes apoptosis of rat cardiac myocytes (H9c2 cells) by downregulating GJIC using CCK-8 Kit, scrape loading/dye transfer assay, Annexin V/PI assays, Western blot analysis and double-immunofluorescence experiments. The results showed that Pb elicited cytotoxicity in a time- and concentration-dependent manner and led to increased apoptosis in a concentration-dependent manner in H9c2 cells. Pb also reduced GJIC in H9c2 cells in a concentration-dependent manner through the downregulation of connexin (Cx) 43. Inhibition of gap junctions by gap junction blocker carbenoxolone disodium (CBX) resulted in increased apoptosis. Furthermore, Pb increased autophagy in a concentration-dependent manner in H9c2 cells, decreasing the distribution of Cx43 on the cell membrane, and targeted Cx43 to autophagosome via light chain 3 (LC3). However, autophagy inhibitor 3-Methyladenine (3-MA) can slow down the downregulation of Cx43 induced by Pb in H9c2 cells. In conclusion, our results provide evidence that Pb-decreased GJIC promotes apoptosis in cardiomyocytes. This is probably because of the fact that Pb-induced autophagy exacerbates GJIC inhibition and downregulation of Cx43.


Real-World Evaluation of Factors for Interstitial Lung Disease Incidence and Radiologic Characteristics in Patients With EGFR T790M-positive NSCLC Treated With Osimertinib in Japan.
Using real-world Japanese postmarketing data, we characterized interstitial lung disease (ILD) development during the second- or later-line osimertinib treatment for EGFR mutation-positive NSCLC. Retrospective radiologic image evaluation of patients developing ILD was also performed. Patients who had ILD events reported as an adverse drug reaction by their physicians and who were assessed as having developed ILD as assessed by an ILD expert committee in Japan were included. Among 3578 patients, 252 ILD events were reported in 245 patients (6.8%) by their attending physicians. The median (range) time to the first onset of ILD after osimertinib treatment initiation was 63.0 (5-410) days, and 29 patients with a fatal outcome were reported. The ILD expert committee assessed 231 of 3578 patients (6.5%) as having ILD. A previous history of nivolumab therapy (adjusted OR: 2.84; 95% confidence interval: 1.98-4.07) and a history or concurrence of ILD (3.51; 2.10-5.87) were identified as factors potentially associated with ILD onset during osimertinib treatment. In patients who had received a previous nivolumab treatment, the number and proportion of patients developing ILD were highest for patients who discontinued nivolumab treatment within the first month before initiating osimertinib; trends for decreasing incidence and proportion were observed, with an increasing duration between the end of nivolumab treatment and the initiation of osimertinib treatment. The frequency of ILD was consistent with the known osimertinib safety profile in the Japanese population. A history or concurrence of ILD and history of previous nivolumab therapy are factors potentially associated with ILD onset during osimertinib treatment.


Inhibition of mitochondrial fission and iNOS in the dorsal vagal complex protects from overeating and weight gain.
The dorsal vagal complex (DVC) senses insulin and controls glucose homeostasis, feeding behaviour and body weight. Three-days of high-fat diet (HFD) in rats are sufficient to induce insulin resistance in the DVC and impair its ability to regulate feeding behaviour. HFD-feeding is associated with increased dynamin-related protein 1 (Drp1)-dependent mitochondrial fission in the DVC. We investigated the effects that altered Drp1 activity in the DVC has on feeding behaviour. Additionally, we aimed to uncover the molecular events and the neuronal cell populations associated with DVC insulin sensing and resistance. Eight-week-old male Sprague Dawley rats received DVC stereotactic surgery for brain infusion to facilitate the localised administration of insulin or viruses to express mutated forms of Drp1 or to knockdown inducible nitric oxide synthase (iNOS) in the NTS of the DVC. High-Fat diet feeding was used to cause insulin resistance and obesity. We showed that Drp1 activation in the DVC increases weight gain in rats and Drp1 inhibition in HFD-fed rats reduced food intake, weight gain and adipose tissue. Rats expressing active Drp1 in the DVC had higher levels of iNOS and knockdown of DVC iNOS in HFD-fed rats led to a reduction of food intake, weight gain and adipose tissue. Finally, inhibiting mitochondrial fission in DVC astrocytes was sufficient to protect rats from HFD-dependent insulin resistance, hyperphagia, weight gain and fat deposition. We uncovered new molecular and cellular targets for brain regulation of whole-body metabolism, which could inform new strategies to combat obesity and diabetes.


Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth.
Stem cells from human exfoliated deciduous teeth (SHEDs) are a promising source for tissue engineering and stem cell transplantation. However, long-term in vitro culture and expansion lead to the loss of stemness of SHEDs, compromising their therapeutic benefits. Hypoxia plays an essential role in controlling the stem cell behavior of mesenchymal stem cells (MSCs). Thus, this study aimed to investigate the effects of cobalt chloride (CoCl2), a hypoxia-mimetic agent, on the stem cell marker expression and osteogenic differentiation of SHEDs. SHEDs were cultured with or without 50 or 100 μM CoCl2. Their proliferation, apoptosis, stem cell marker expression, migration ability, and osteogenic differentiation were examined. Culture with 50 and 100 μM CoCl2 increased the hypoxia-inducible factor-1 alpha (HIF-1α) protein levels in a dose-dependent manner in SHEDs without inducing significant cytotoxicity. This effect was accompanied by an increase in the proportion of STRO-1+ cells. CoCl2 significantly increased the expression of stem cell markers (OCT4, NANOG, SOX2, and c-Myc) in a dose-dependent manner. The migration ability was also promoted by CoCl2 treatment. Furthermore, SHEDs cultured in osteogenic medium with CoCl2 showed a dose-dependent reduction in alkaline phosphatase (ALP) activity and calcium deposition. The expression of osteogenic-related genes was also suppressed by CoCl2, especially in the 100-μM CoCl2 group. In conclusion, CoCl2 increased the expression of stem cell markers and inhibited the osteogenic differentiation of SHEDs. These findings may provide evidence supporting the use of in vitro hypoxic environments mimicked by CoCl2 in assisting the clinical application of SHEDs.


Use of an in vivo oxygen electrode to determine the effect of hemorrhagic shock on liver oxygen tension.
Measurement of arterial and liver tissue oxygen tension (PO2) in animals subjected to hemorrhagic shock demonstrates a significant (p less than 0.001) decrease in tissue PO2 while PaO2 remains essentially unchanged. In fact, marked increase in PaO2 fail to increase tissue PO2 to control levels, demonstrating that the act of increasing FIO2 and/or PaO2 is inadequate treatment of decreased tissue oxygenation in marginal or low flow states. Measurement of tissue PO2 in a variety of clinical situations seems warranted to allow alterations of therapy to improve flow when indicated by inadequate tissue oxygenation. The application of this simple but extremely useful technic should result in improved survival rates in critically ill patients.


Parameter estimation for nonlinear frequency dependent attenuation in soft tissue.
Most current attenuation estimation methods are based on an assumption that tissue attenuation is linearly frequency dependent. For tissues exhibiting nonlinear attenuation, such methods could produce biased results. This paper describes a new time-domain, amplitude method for estimating two parameters, beta and n, in nonlinear attenuation. In this method, echo signal of each A-line is first filtered in parallel by a bank of narrow-bandpass filters. Attenuation values at filter center frequencies can be calculated from the envelope peaks of each filtered narrowband signal, and beta and n are then estimated from these attenuation values. A quantitative study of the estimation uncertainty indicates that there is a significant increase in the variance of beta estimate when the attenuation model is changed from linear to nonlinear. The analysis yields insights into the tradeoff between estimation accuracy and estimation precision when tissue attenuation is only slightly deviated from linearity.


Death Notification in Italian Critical Care Unites and Emergency Services. A Qualitative Study with Physicians, Nurses and Relatives.
This qualitative study was conducted in critical care units and emergency services and was aimed at considering the death notification (DN) phenomenology among physicians (notifiers), patient relatives (receivers) and those who work between them (nurses). Through the qualitative method, a systemic perspective was adopted to recognise three different categories of representation: 23 clinicians, 13 nurses and 11 family members of COVID-19 victims were interviewed, totalling 47 people from all over Italy (25 females, mean age: 46,36; SD: 10,26). With respect to notifiers, the following themes emerged: the changes in the relational dimension, protective factors and difficulties related to DN. With respect to receivers, the hospital was perceived as a prison, bereavement between DN, lost rituals and continuing bonds. Among nurses, changes in the relational dimension, protective factors and the impact of the death. Some common issues between physicians and nurses were relational difficulties in managing distancing and empathy and the support of relatives and colleagues. The perspective of receivers showed suffering related to loss and health care professionals' inefficacy in communication. Specifically, everyone considered DNs mismanaged because of the COVID-19 emergency. Some considerations inherent in death education for DN management among health professionals were presented.


Climate adaptive hospital: A systematic review of determinants and actions.
Climate change is among the most renowned concerns of the current century, endangering the lives of millions of people worldwide. To comply with the United Nations Climate Change Conference (COP21), hospitals should be on track to reduce greenhouse gas emissions. Although hospitals contribute to climate change by emitting greenhouse gases, they are also affected by the health consequences of climate change. Despite all the guidance provided, hospitals need more radical measures to confront climate change. The current study was carried out to examine the components of hospitals' adaptation to climate change and to review measures to confront climate change in hospitals. This systematic review was designed and carried out in 2020. The required information was collected from international electronic databases including Scopus, PubMed, Web of Science, EMBASE, and Google Scholar. Moreover, Iranian datasets such as Scientific Database (SID), Irandoc, Magiran, and IranMedex were reviewed. No restriction was considered in the methodology of the study. For the relevant thesis, the ProQuest database was also explored. The related sources were examined and the Snowball method was applied to find additional related studies. The research team also reviewed other accessible electronic resources, such as international guidelines and academic websites. The checklist of the Joanna Briggs Institute (JBI, 2017) was employed in order to evaluate the quality of the included papers. The studies published until June1, 2020, were included in the study. Of 11,680 published documents in the initial search, the full-texts of 140 were read after evaluating the titles and abstracts, of which 114 were excluded due to lack of sufficient information related to countermeasures in hospitals. Finally, the full-texts of 26 studies were reviewed to extract the required components. Two strategies were found, including climate change mitigation and climate change adaptation, with 13 components including water, wastewater, energy, waste, green buildings, food, transportation, green purchasing policy, medicines, chemicals and toxins, technology, sustainable care models, and leadership in hospitals were identified as affecting these measures and strategies. Considering the significance of climate change and strategies to confront it as one of the current challenges and priorities in the world, it is necessary to develop a framework and model to reduce the effects of climate change and adapt to climate changes in hospitals and other health centers. The identification and classification of the measures and components, influencing hospital adaptability and solutions for reducing the climate change impacts could be the first stage in developing this strategy. This is because it is impossible to create this framework without identifying these factors and their mutual impacts at the first. In the present study, through a systematic review using a comprehensive approach, the related components were explored and divided into two categories, including measures to reduce the effects and measures to adapt to climate change. The results of this study can be useful in developing a comprehensive action model to reduce greenhouse gas emissions and adapt hospitals to climate change.