Left ventricular torsion abnormalities in patients after the arterial switch operation for transposition of the great arteries with intact ventricular septum.
The arterial switch operation (ASO) is currently the treatment of choice for infants with transposition of the great arteries (TGA). Little is known, however, about the alteration of anatomic left ventricular (LV) torsional mechanics after the operation. This study sought to evaluate LV torsion in patients of transposition of the great arteries with intact ventricular septum (TGA/IVS) using speckle tracking echocardiography. Echocardiographic images were prospectively acquired in 32 infants (age range, 0.5-60 months) who successfully underwent ASO repair at about 1 month of age and in 48 normal controls. They were divided into early and late categories according to the age at the time of the study. The LV peak systolic torsion and systolic twisting and diastolic untwisting velocities were determined by speckle tracking. Mitral inflow velocity obtained by Pulsed-wave Doppler and mitral annular velocities drawn by septal tissue Doppler were also analyzed. Compared with controls, the early postoperative group (TGA1) had significantly higher septal E/e' (P=0.000). In contrast, septal e' velocity (P=0.000), LV peak apical rotation (P=0.01), twist (P=0.02) and peak untwisting velocity (PUV) (P=0.001) were lower in patients than in controls. For the normal younger group (Control1), PUV correlated positively with e' (r=0.68, P<0.001). No significant difference in LV twisting and untwisting was noted between the TGA2 and Control2. Two dimensional speckle tracking echocardiography may sensitively detect impaired LV torsional mechanics in patients with TGA/IVS early after ASO, and the impairment of LV relaxation leads to increased LV filling pressure which is consistent with higher E/e'. However, all patients recovered well thereafter and the overall midterm outcome of ASO is satisfactory.


Gut microbiota-bile acid-skeletal muscle axis.
The gut microbiota represents a 'metabolic organ' that can regulate human metabolism. Intact gut microbiota contributes to host homeostasis, whereas compositional perturbations, termed dysbiosis, are associated with a wide range of diseases. Recent evidence demonstrates that dysbiosis, and the accompanying loss of microbiota-derived metabolites, results in a substantial alteration of skeletal muscle metabolism. As an example, bile acids, produced in the liver and further metabolized by intestinal microbiota, are of considerable interest since they regulate several host metabolic pathways by activating nuclear receptors, including the farnesoid X receptor (FXR). Indeed, alteration of gut microbiota may lead to skeletal muscle atrophy via a bile acid-FXR pathway. This Review aims to suggest a new pathway that connects different mechanisms, involving the gut-muscle axis, that are often seen as unrelated, and, starting from preclinical studies, we hypothesize new strategies aimed at optimizing skeletal muscle functionality.


Investigating the association between temperature and hospital admissions for major psychiatric diseases: A study in Greece.
Evidence has emerged regarding the role of seasonality and several meteorological parameters on bipolar disorder, schizophrenia and depression. We investigated the relationship between ambient and apparent temperature and hospital admissions of major psychiatric diseases in a psychiatric clinic of a General Hospital situated in Northern Greece during 2013-19. Temperature data was provided by the National Observatory of Athens and diagnosis for psychotic, schizophrenic, manic and bipolar and unipolar depression were retrieved from medical records. A total of 783 admissions were recorded. Poisson regression models adjusted for time trends were applied to analyze the impact of temperature on monthly admissions. A summer peak was observed for the bipolar disorder, irrespectively of substance/alcohol use status. Seasonality emerged also for psychotic and schizophrenic patients with a through in winter. An increase of 1 °C in either ambient or apparent temperature was associated with an increase 1-2% in the monthly admissions in most outcomes under investigation. Alcohol and drug abuse did not modify this effect. Although our results indicate effects of temperature on psychiatric admissions, they are not consistent across subgroups populations and need to be replicated by other methodologically superior studies.


Thyrostimulin-TSHR signaling promotes the proliferation of NIH:OVCAR-3 ovarian cancer cells via trans-regulation of the EGFR pathway.
Gonadotropin signaling plays an indispensable role in ovarian cancer progression. We previously have demonstrated that thyrostimulin and thyroid-stimulating hormone receptor (TSHR), the most ancient glycoprotein hormone and receptor pair that evolved much earlier than the gonadotropin systems, co-exist in the ovary. However, whether thyrostimulin-driven TSHR activation contributes to ovarian cancer progression in a similar way to gonadotropin receptors has never been explored. In this study, we first found that TSHR is expressed in both rat normal ovarian surface epithelium and human epithelial ovarian cancers (EOCs). Using human NIH:OVCAR-3 as a cell model, we demonstrated that thyrostimulin promotes EOC cell proliferation as strongly as gonadotropins. Thyrostimulin treatment not only activated adenylyl cyclase and the subsequent PKA, MEK-ERK1/2 and PI3K-AKT signal cascades, but also trans-activated EGFR signaling. Signaling dissection using diverse inhibitors indicated that EOC cell proliferation driven by thyrostimulin-TSHR signaling is PKA independent, but does require the involvement of the MEK-ERK and PI3K-AKT signal cascades, which are activated mainly via the trans-activation of EGFR. Thus, not only have we proved that this ancient glycoprotein hormone system is involved in NIH:OVCAR-3 cell proliferation for the first time, but also that it may possibly become a novel oncotarget when studying ovarian cancer.


Model systems for experimental studies: retinal ganglion cells in culture.
Glaucomatous optic neuropathy is the most common optic nerve disease. The mechanisms by which retinal ganglion cells (RGCs) die in glaucoma are becoming better understood, but are still poorly defined. Elucidating the pathways that connect risk factors for glaucoma (e.g., elevated intraocular pressure) and RGC death is difficult in patients because of ethical and practical constraints. Even in experimental animals, single-cell observations and cell-cell interactions can be tricky to tease apart. For these reasons, it is helpful to use cell and tissue culture models for studying RGCs and other cellular constituents of the optic nerve. This chapter describes the advantages and disadvantages of several commonly used methods for preparing and studying these cultures, including those most relevant to glaucomatous optic neuropathy.


Artemisinin ameliorates intestinal inflammation by skewing macrophages to the M2 phenotype and inhibiting epithelial-mesenchymal transition.
Inflammatory bowel disease (IBD) is a self-destructive intestinal disease whose etiology is unclear but complex and the effective treatment is deficient. Increasing evidences have indicated that immune dysfunction and epithelial-mesenchymal transition (EMT)-related intestinal mucosal barrier impaired hold critical position in the pathogenesis of IBD. Artemisinin (ART) is a sesquiterpenoid compound extracted from Chinese herbal medicine which has good immunomodulatory effects. Studies have shown that artemisinin and its analogues have therapeutic effects on a variety of tumors and immune-related disorders. The purpose of current study was to research the effect and mechanism about artemisinin-induced macrophage polarization to M2 phenotype and inhibiting the process of EMT. In vitro, the anti-inflammatory effect of artemisinin is mainly verified by RAW264.7 cells and tissue (colon tissue and PBMC) from CD patients with active intestinal inflammation. RAW264.7 cells stimulated with LPS to induce inflammatory state and ART were used as therapeutic treatment in different concentration. Then the expression levels of pro-inflammatory factors, macrophage polarization and ERK pathway were analyzed. Colon tissue and PBMC from CD patients were treated with ART in different concentrations and macrophage polarization, pro-inflammatory factors expression, EMT-related protein were analyzed. In vivo, DSS-induced colitis mice were treated by ART for seven days. The DAI score was calculated and the colons and spleens were harvested after the animals were sacrificed. The expression of macrophage markers and EMT-related markers in the intestines of mice in each group were monitored by qPCR and western blot. ART treatment could decrease the levels of pro-inflammatory coefficient expressed in theRAW264.7 cells and human PBMC. Moreover, ART could ameliorate the intestinal inflammation in vivo through down-regulating the expression of pro-inflammatory factors, promoting macrophage polarization to M2 phenotype and inhibiting the process of EMT. Taken together, our findings demonstrated that artemisinin might ameliorate inflammation by inducing macrophage polarization to M2 phenotype and inhibiting the process of EMT, suggesting that ART may be applied to the rehabilitation of IBD in the future.


Gluconic acid as a chelator to improve clarity of skim milk powder dispersions at pH 3.0.
Clear acidic protein beverages have a niche market. Acidification of skim milk powder (SMP) dispersions to pH 3.0 using citric acid (CA) lowers turbidity but the dispersion remains translucent. The present study aimed at comparing physicochemical properties of 5% w/v SMP dispersions acidified to pH 3.0 using chelating gluconic acid (GA) and CA and non-chelating hydrochloric acid. GA was the most effective in reducing the dispersion turbidity to 394 NTU at pH 3.0, which was further reduced to 248 NTU after heating at 90 °C for 2 min resulting in transparent dispersions. The better chelating ability of GA than CA was supported by the higher extent of dissolved CCP in serum phase. The aggregation of dissociated caseins was not observed for the GA treatment based on transmission electron microscopy. The findings from this study may be used to produce clear casein-based protein beverages.


Health insurance and treatment of adolescents with co-occurring major depression and substance use disorders.
The goals of this study were to identify treatment rates among adolescents with co-occurring major depressive episode (MDE) and substance use disorder (SUD), and to examine the role of health insurance in the treatment of these disorders. Seven years of cross-sectional data (2004-2010) were pooled from the National Survey on Drug Use and Health to derive a nationally representative sample of 2,111 adolescents who had both a past-year MDE and SUD and whose insurance status was known. The associations of public and private insurance with MDE and SUD treatment were examined using multinomial logistic regressions that controlled for health status and sociodemographic variables. Less than one-half (48%) of adolescents received any form of MDE treatment in the past year, and only 10% received any form of SUD treatment. Only 16% of adolescents who received MDE treatment also received SUD treatment. Relative to no insurance, public insurance was associated with an increased likelihood of receiving MDE treatment alone, but not with an increased likelihood of receiving both MDE and SUD treatment. Involvement in the criminal justice system was the major factor affecting the likelihood that an adolescent would receive both MDE and SUD treatment, as opposed to either no treatment or treatment for MDE alone. Exceptionally low rates of SUD treatment were observed in this high-risk sample. Study findings highlight a missed opportunity to assess and to treat SUD among adolescents with co-occurring MDE and SUD who have received some form of MDE treatment in the past year.


Colonic bleeding in the elderly.
In the elderly population bleeding from the colon is not unusual. In evaluating a patient with colonic bleeding, the rate of bleeding should be assessed, and the possibility of upper gastrointestinal and anorectal bleeding should be excluded. The most common cause of massive bleeding from the colon in the elderly patient is diverticulosis, and the next most common cause is angiodysplasia. A number of other less common causes of bleeding should be excluded when making the diagnosis. If angiography is employed and the bleeding site is identified, initial therapy can be started concurrently by either injecting a vasopressor drug intraarterially or by embolization. Failure to stop the bleeding leads to surgery as the next step. If the bleeding stops spontaneously, one can expect recurrence later; therefore an interval work-up is stressed to identify the anatomic area of suspected bleeding. Preoperative identification of the bleeding site is imperative so that a "blind resection" can be avoided.


Transforming nursing workflow, part 2: the impact of technology on nurse activities.
To assess the impact of new technology on nurse workflow, nurses at 2 hospitals were observed before and after implementation of an electronic medication charting system. In part 1 (September 2010 issue), we discussed the chaotic nature of nurse activities and its implications on transforming workflow. Numerous studies have documented the impact of technology on performance and satisfaction, but technology's impact on the frequency, duration, and pattern of activities is less understood. These patterns are important to the development of new care models. Observers shadowed nurses at 2 hospitals before and after the implementation of an electronic medication charting system. A total of 196 hours of observation was recorded at one site, and 185 hours at the other site. Analysis of variance revealed a number of significant differences in the time spent on a variety of activities, but the duration and frequency of nurse activities were not drastically altered by the additional technology. Computer use increased; however, the impact was evenly distributed among other activities. More importantly, time with patients and verbal communication remained unchanged as nurses seemed to incorporate the new requirements into their normal routine.


Oxidative potential associated with water-soluble components of PM2.5 in Beijing: The important role of anthropogenic organic aerosols.
Oxidative stress is the mainstream toxicological mechanism for the adverse health outcomes of ambient aerosols. However, our understanding of the crucial redox-active species affecting the oxidative potential of water-soluble aerosols (OPWS) remains limited. In this study, the OPWS of PM2.5 in Beijing was measured using dithiothreitol (DTT) assay, including DTT consumption rate and ·OH formation rate. OPWS was more closely related to water-soluble organic compounds (WSOC) rather than transition metals. Laboratory simulations were conducted to investigate the effects of individual target species in the context of complex metal-organic interactions. The results showed that reducing WSOC can effectively decrease OPWS, while reducing Cu2+ increased OPWS. Parallel factor analysis demonstrated that OPWS was the most significantly correlated with the highly oxidized humic-like or quinone-like substances. Multiple linear regression showed that aromatic secondary organic carbon (SOC) (34.4%), other primary combustion sources of WSOC (20.0%), primary biomass burning WSOC (19.8%), transition metal ions (12.9%) and biomass burning SOC (12.8%) made significant contributions to DTTV. In addition to the anthropogenic sources of WSOC, the aged biogenic SOC also contributed to OHV, particularly in summer. Reducing anthropogenic WSOC was the key to the effective control of OPWS of PM2.5 in Beijing.


Comprehensive metabolomic profiling of osteosarcoma based on UHPLC-HRMS.
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. An increasing number of studies have demonstrated that tumor proliferation and metastasis are closely related to complex metabolic reprogramming. However, there are limited data to provide a comprehensive metabolic picture of osteosarcoma. Our study aims to identify aberrant metabolic pathways and seek potential adjuvant biomarkers for osteosarcoma. Serum samples were collected from 65 osteosarcoma patients and 30 healthy controls. Nontargeted metabolomic profiling was performed by liquid chromatography-mass spectrometry (LC-MS) based on univariate and multivariate statistical analyses. The OPLS-DA model analysis identified clear separations among groups. We identified a set of differential metabolites such as higher serum levels of adenosine-5-monophosphate, inosine-5-monophosphate and guanosine monophosphate in primary OS patients compared to healthy controls, and higher serum levels of 5-aminopentanamide, 13(S)-HpOTrE (FA 18:3 + 2O) and methionine sulfoxide in lung metastatic OS patients compared to primary OS patients, revealing aberrant metabolic features during the proliferation and metastasis of osteosarcoma. We found a group of metabolites especially lactic acid and glutamic acid, with AUC values of 0.97 and 0.98, which could serve as potential adjuvant diagnostic biomarkers for primary osteosarcoma, and a panel of 2 metabolites, 5-aminopentanamide and 13(S)-HpOTrE (FA 18:3 + 2O), with an AUC value of 0.92, that had good monitoring ability for lung metastases. Our study provides new insight into the aberrant metabolic features of osteosarcoma. The potential biomarkers identified here may have translational significance.


Educational Needs of Oncology Practitioners in a Regional Cancer Center in the Middle East-Improving the Content of Smoking Cessation Training Programs.
Little is known with regard to perceptions and information needs of oncology practitioners in the Middle East as they pertain to smoking cessation (SC) support for cancer patients. We sought to assess these in a regional cancer center. A survey was distributed to oncology practitioners (physicians, nurses, pharmacists, and physio- and respiratory therapists) at King Hussein Cancer Center (Amman, Jordan) for self-completion. The survey included SC-related measures of perceptions, knowledge, and practices. Descriptive statistics and cross tabulations were performed to identify misperceptions and knowledge gaps that could be corrected through continuing education. Findings revealed, among 254 practitioners surveyed, low referral rates to the SC clinic. Negative perceptions about cancer patients who smoke existed (e.g., patients needing smoking to control anxiety; patients' willpower sufficient for quitting; patients not wanting to quit and not needing more information). Substantial knowledge gaps were prevalent with regard to the detrimental outcomes associated with continued tobacco use after a cancer diagnosis and with regard to approved SC medication choices. Our results are useful in identifying topics that need to be highlighted during training and educational efforts in the region and also reinforce the need to avail such efforts in order to improve SC-related knowledge and perceptions.


Unravelling factors associated with malaria parasitaemia among children 6-24 months to inform malaria interventions in Nigeria: evidence from 2021 Malaria Indicator Survey.
As an additional two million malaria cases were reported in 2021 compared to the previous year, concerted efforts toward achieving a steady decline in malaria cases are needed to achieve malaria elimination goals. This work aimed at determining the factors associated with malaria parasitaemia among children 6-24 months for better targeting of malaria interventions. A cross-sectional study analysed 2021 Nigeria Malaria Indicator Survey dataset. Data from 3058 children 6-24 months were analyzed. The outcome variable was children 6-24 months whose parasitaemia was determined using a rapid diagnostic test (RDT). Independent variables include child age in months, mothers' age, mothers' education, region, place of residence, household ownership and child use of insecticide-treated net (ITN), exposure to malaria messages and knowledge of ways to prevent malaria. Logistic regression analysis was conducted to examine possible factors associated with malaria parasitaemia in children 6-24 months. Findings revealed that 28.7% of the 3058 children aged 6-24 months tested positive for malaria by RDT. About 63% of children 12-17 months (aOR = 1.63, 95% CI 1.31-2.03) and 91% of children 18 to 24 months (aOR = 1.91, 95% CI 1.51-2.42) were more likely to have a positive malaria test result. Positive malaria test result was also more likely in rural areas (aOR = 1.79, 95% CI 2.02-24.46), northeast (aOR = 1.54, 95% CI 1.02-2.31) and northwest (aOR = 1.63, 95% CI 1.10-2.40) region. In addition, about 39% of children who slept under ITN had a positive malaria test result (aOR = 1.39 95% CI 1.01-1.90). While children of mothers with secondary (aOR = 0.40, 95% CI 0.29-0.56) and higher (aOR = 0.26, 95% CI 0.16-0.43) levels of education and mothers who were aware of ways of avoiding malaria (aOR = 0.69, 95% CI 0.53-0.90) were less likely to have a malaria positive test result. As older children 12 to 24 months, children residing in the rural, northeast, and northwest region are more likely to have malaria, additional intervention should target them in an effort to end malaria.


Investigate the multipath erasure of nitrobenzene over nanoscale zero-valent-iron/N-doped biochar hybrid with extraordinary reduction performance.
In this study, the facile carbothermal reduction method was enforced using urea as dopant to modify the structure and chemical composition of nanoscale zero-valent-iron/biochar hybrid thereby boosting its reduction performance. Through fine-tuning the N-doped amount, the optimal nZVI/N-doped BC was obtained, which exhibited more active sites (nZVI, persistent free radicals (PFRs), pyrrolic-N) and superior electrochemical conductivity. With these blessings, the electrons originating from galvanic cell reaction could zip along the highway within the hybrid. Taking nitrobenzene (NB) as the target pollutant, the quantitative analysis revealed that the NB reduction and adsorption removal efficiency were dramatically improved by 2.42 and 2.78 times, respectively. What's more, combining the in-situ experimental detection and theoretical calculations, unexpected NB reductive multipath with respect to PFRs and pyrrolic-N accelerating the Fe3+/Fe2+ cycle within the nZVI/N-doped BC system was decoded. The enhancement of Fe3+/Fe2+ cycle improved the electron utilization efficiency and maintained the reduction reactivity of the hybrid. This work raised awareness of the mechanisms regarding the reduction performance of nZVI/N-doped BC elevated by N-doped and the pollutant reductive pathway within the system, uncovered the dusty roles of PFRs and N-species during the reduction process.


Photorefractive keratectomy (PRK) Prediction, Examination, tReatment, Follow-up, Evaluation, Chronic Treatment (PERFECT) protocol - A new algorithmic approach for managing post PRK haze.
The aim of this study was to discuss the possible risk factors predisposing to post photorefractive keratectomy (PRK) haze formation and develop and validate a risk scoring system, so that this could be applied to our clinical practice as an algorithmic approach. Study was divided into 2 arms, in the retrospective arm we looked at 238 eyes of patients undergoing PRK where certain presumed risk factors from literature and clinical experience were identified and statistical significance of association was studied in the development of corneal haze. The risk scoring system was applied to the 450 eyes in the prospective arm for validation. This was then used to formulate an algorithmic approach to manage post-PRK haze. 22 out of 238 eyes in the retrospective arm developed haze where risk factors such as contact lens intolerance, altered tear film break up time, meibomian gland drop out and vitamin d levels were significantly associated with post-PRK haze (p < 0.05) and these factors were identified in the prospective arm. Treatment of these modifiable factors led to a significant reduction in post-PRK haze. Thus identifying and treating risk factors of haze in patients undergoing PRK could improve surgical outcomes and patient satisfaction.


Hydrophobicity and molecular mass-based separation method for autoantibody discovery from mammalian total cellular proteins.
Serum autoantibody profiles are unique to individuals and reflect the level and history of autoimmunity and tumor immunity. The identification of autoantibody biomarkers is critical for the development of immune monitoring systems for immune-related disorders. Here, we present a practical method for large-scale autoantibody discovery using total cellular proteins from cultured mammalian cells. We found that nucleic acid-free and fully denatured water-soluble total cellular proteins from mammalian cells were superior, allowing precise separation by reversed-phase HPLC after preparing a large set of homogeneous total cellular proteins. After separating the proteins based on hydrophobicity, the fractionated samples were subjected to molecular mass analysis using conventional SDS-PAGE. The resulting two-dimensional gel electrophoresis was successfully employed for immune blotting and LC-MS/MS analysis. All procedures, including TRIzol-based total cellular protein extraction, solubilization of denatured proteins, reversed-phase HPLC separation, and SDS-PAGE, were highly reproducible and easily scalable. We propose this novel two-dimensional gel electrophoresis system as an alternative proteomics-based methodology suitable for large-scale autoantibody discovery.


Impact of an electronic alert notification system embedded in radiologists' workflow on closed-loop communication of critical results: a time series analysis.
Optimal critical test result communication is a Joint Commission national patient safety goal and requires documentation of closed-loop communication among care providers in the medical record. Electronic alert notification systems can facilitate an auditable process for creating alerts for transmission and acknowledgement of critical test results. We evaluated the impact of a patient safety initiative with an alert notification system on reducing critical results lacking documented communication, and assessed potential overuse of the alerting system for communicating results. We implemented an alert notification system-Alert Notification of Critical Results (ANCR)-in January 2010. We reviewed radiology reports finalised in 2009-2014 which lacked documented communication between the radiologist and another care provider, and assessed the impact of ANCR on the proportion of such reports with critical findings, using trend analysis over 10 semiannual time periods. To evaluate potential overuse of ANCR, we assessed the proportion of reports with non-critical results among provider-communicated reports. The proportion of reports with critical results among reports without documented communication decreased significantly over 4 years (2009-2014) from 0.19 to 0.05 (p<0.0001, Cochran-Armitage trend test). The proportion of provider-communicated reports with non-critical results remained unchanged over time before and after ANCR implementation (0.20 to 0.15, p=0.45, Cochran-Armitage trend test). A patient safety initiative with an alert notification system reduced the proportion of critical results among reports lacking documented communication between care providers. We observed no change in documented communication of non-critical results, suggesting the system did not promote overuse. Future studies are needed to evaluate whether such systems prevent subsequent patient harm.


Buffer standards for the physiological pH of the zwitterionic compound of 3-(N-morpholino)propanesulfonic acid (MOPS) from T = (278.15 to 328.15) K.
This paper reports the pH values of five NaCl-free buffer solutions and eleven buffer compositions containing NaCl at I = 0.16 mol·kg(-1). Conventional pa(H) values are reported for sixteen buffer solutions with and without NaCl salt. The operational pH values have been calculated for five buffer solutions and are recommended as pH standards at T = (298.15 and 310.15) K after correcting the liquid junction potentials. For buffer solutions with the composition m(1) = 0.04 mol·kg(-1), m(2) = 0.08 mol·kg(-1), m(3) = 0.08 mol·kg(-1) at I = 0.16 mol·kg(-1), the pH at 310.15 K is 7.269, which is close to 7.407, the pH of blood serum. It is recommended as a pH standard for biological specimens.


Sulfur participation in [3,3]-sigmatropic rearrangements.
The thio-Claisen rearrangement is a general and facile process that is often advantageous overthe standard Claisen rearrangement. Several asymmetric variants of the thio-Claisen rearrangement havebeen reported. The rearrangement of sulfonium salts and sulfoxides takes place even more readily. Alkenylsulfoxides and sulfilimines undergo a highly stereocontrolled cyclization to lactones and lactams,respectively, upon reaction with haloketenes; this synthetically useful process entails a [3,3]-sigmatropicrearrangement of a zwitterionic intermediate. Sulfur-containing functionalities located at the peripheryof the Claisen substrates exert a powerful influence on the outcome of the process.


Posttraumatic Stress Syndrome and Implications for Practice in Critical Care Nurses.
Posttraumatic stress disorder (PTSD) is a complex, often debilitating, disorder that has far-reaching effects, including anxiety, depression, burnout, and compassion fatigue. Working as a critical care unit nurse can be physically and emotionally demanding. Critical care nurses are at increased risk of developing PTSD compared with general care nurses. Employers are also affected due to increased rates of attrition, absenteeism, and general decreased quality in patient care. There is conflicting evidence related to which factors contribute to PTSD but increased resilience holds the most promise for preventing PTSD and its detrimental effects on critical care nurses.


An ancient plant for the synthesis of a novel carbon dot and its applications as an antibacterial agent and probe for sensing of an anti-cancer drug.
An innovative, facile, low- cost and one-pot hydrothermal synthesis was developed for preparing a high fluorescence carbon dots (CDs). In this report for the first time, Lawsonia inermis (Henna) plant as a carbon source was used to produce CDs without adding any chemical reagent and it was characterized by different techniques. The as-synthesized CDs exhibit high stability under various conditions and exceptionally solubility in hydrophilic solvents such as water and ethanol. In addition, the CDs were employed as a biocompatible probe for determination of methotrexate (MTX) in the range of 0.02 μmol L-1 to 18 μmol L-1 with a detection limit as 7 nmol L-1. Highly selective and sensitive determination of MTX was carried out through the fluorescence resonance energy transfer (FRET) mechanism. It is noteworthy that, the antibacterial studies of this CDs lead to interesting results which suggested Henna CDs kill Gram-positive and Gram-negative bacteria like an antibiotic drug. Also, compared with the henna plant, CDs show antibacterial properties in much lower concentrations.


Gas exchange responses of Chesapeake Bay tidal marsh species under field and laboratory conditions.
Laboratory and field gas exchange measurements were made on C3 (Scirpus olneyi Gray) and C4 (Spartina patens (Ait.) Mahl., Distichlis spicata (L.) Green) species from an irregularly flooded tidal marsh on the Chesapeake Bay. Laboratory measurements were made on plants grown from root stocks that were transplanted to a greenhouse and grown under high light and high nutrient conditions. The two C4 species were similar in their laboratory gas exchange characteristics: both had higher net carbon exchange rates, higher mesophyll conductances, higher photosynthetic temperature optima and lower leaf conductances than the C3 species. The laboratory photosynthetic water use efficiency of the C4 species was approximately three times that of the C3 species.Field gas exchange responses of the above species were measured in situ a Chesapeake Bay tidal marsh. Despite differences in biological potential measured in the laboratory, all three species had similar in situ carbon exchange rates on a leaf area basis. On a dry weight basis, leaves of the two C4 species had about 1.4 times higher light saturated CO2 assimilation rates than the C3 species. Light saturation of CO2 exchange occurred at photosynthetic photon flux densities of 80 n Einstein cm-2s-1, compared with 160 n Einstein cm -2s-1 in the laboratory grown plants. Spartina patens and Scirpus olneyi had similar daily CO2 assimilation rates, but the daily transpiration rate of the C3 species was almost twice that of the C4 species. Spartina patens showed greater seasonal decrease in photosynthesis than Distichlis spicata and Scirpus olneyi. The two C4 grass species maintained higher mesophyll conductances and photosynthetic water use efficiencies than the C4 sedge.


Psychiatric issues in medical-surgical disaster casualties: a consultation-liaison approach.
Psychiatrists can increase the efficacy of their response to disaster victims in the immediate aftermath of a disaster if they utilize a consultation-liaison approach to assessment and management of casualties. Medical-surgical disaster responders use an algorithmic, stepwise approach to assess disaster or trauma victims. This approach ensures that patients with life-threatening injuries who are not expectant are treated first. Then, secondary physical assessments ensure proper triage of other victims so that disaster response resources are used most wisely. A tertiary psychiatric assessment can assist with differential diagnosis of post-disaster neuropsychiatric symptoms and signs to ensure valuable medical-surgical resources are targeted to the correct patients. Psychiatric triage can also identify those victims most in need of early preventive and therapeutic psychiatric intervention.


Diagnostic Accuracy of Noninvasive Bone Turnover Markers in Renal Osteodystrophy.
Bone biopsy remains the gold standard for diagnosing renal osteodystrophy as comparable noninvasive alternatives have yet to be established. This study investigated the diagnostic accuracy of biochemical markers of skeletal remodeling to predict bone turnover. Cross-sectional retrospective diagnostic test study. Patients with chronic kidney disease glomerular filtration rate categories 4-5, including patients treated with dialysis (G4-G5D) and kidney transplant recipients with successful transiliac bone biopsies. Bone turnover as determined by bone histomorphometry was compared with the following biochemical markers: full-length (amino acids 1-84) "biointact" parathyroid hormone (PTH), bone-specific alkaline phosphatase (BsAP), intact procollagen type I N-terminal propeptide (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b). Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC), sensitivity, specificity, and negative and positive predictive values. Optimal diagnostic cutoffs were determined in an exploration cohort (n = 100) and validated in a separate cohort (n = 99). All biomarkers differed across categories of low 33 (17%), normal 109 (55%), and high 57 (29%) bone turnover. AUC values were in the range of 0.75-0.85. High negative predictive values (≥90%) were found for both high and low bone turnover, indicating the ability to rule out both conditions using the suggested biomarker cutoffs. The highest diagnostic performances were seen with combinations of biomarkers, with overall diagnostic accuracies of 90% for high turnover, and 78% for low turnover. Results were comparable for kidney transplant candidates and recipients in a sensitivity analysis. The single-center approach and heterogeneity of the study cohort are main limitations of this study. We conclude that the diagnostic performance of biochemical markers of bone turnover is acceptable, with clinical utility in ruling out both high and low turnover bone disease.


Recasting developmental evolution in terms of genetic pathway and network evolution ... and the implications for comparative biology.
The morphological features of complex organisms are the outcomes of developmental processes. Developmental processes, in turn, reflect the genetic networks that underlie them. Differences in morphology must ultimately, therefore, reflect differences in the underlying genetic networks. A mutation that affects a developmental process does so by affecting either a gene whose product acts as an upstream controlling element, an intermediary connecting link, or as a downstream output of the network that governs the trait's development. Although the immense diversity of gene networks in the animal and plant kingdoms would seem to preclude any general "rules" of network evolution, the material discussed here suggests that the patterns of genetic pathway and network evolution actually fall into a number of discrete modes. The potential utility of this conceptual framework in reconstructing instances of developmental evolution and for comparative neurobiology will be discussed.


Competitive aptasensor with gold nanoparticle dimers and magnetite nanoparticles for SERS-based determination of thrombin.
It is known that the intensity of surface-enhanced Raman scattering (SERS) of monomeric gold nanoparticles (GNPs) is insufficient for ultrasensitive analysis. The authors describe dimeric GNPs for use in a competitive SERS and aptamer based assay for thrombin. The reagent 1,2-bis(4-pyridyl) ethylene serves as both the coupling agent and the Raman reporter on the GNP dimers. In the presence of thrombin, the hybridization of two aptamers, one attached to the GNP dimers, the other to magnetic nanoparticles, is competitively prevented. This method takes advantage of the unique "hot spots" of the GNP dimers to amplify the Raman signal. This results in an ultra-sensitive thrombin assay when compared to assays using GNP monomers. The limit of detection is as low as 1 fM of thrombin. The Raman intensity, best measured at 1612 cm-1, increases linearly in the 1 fM to 10 nM thrombin concentration range. The method was applied to the determinaiton of thrombin in spiked simulated body fluid and human serum. Graphical abstract This method takes advantage of the unique "hot spots" of the gold nanoparticle dimers to amplify the Raman signal. The dimers are linked to the magnetic nanoparticles via an aptamer. The use of both competitive displacement and magnetic separation greatly improves the sensitivity of the thrombin assay.


Health benefits of anthocyanin-containing foods, beverages, and supplements have unpredictable relation to gastrointestinal microbiota: A systematic review and meta-analysis of random clinical trials.
Anthocyanins are a type of natural pigment that has numerous health benefits. In recent years, the interaction of anthocyanins with gastrointestinal (GI) microbiota has been presented as a viable paradigm for explaining anthocyanin activities. The current study performed a systematic review and meta-analysis to determine the potential modulation of GI microbiota by anthocyanins in human health improvement. Clinical trials were retrieved from PubMed, Cochrane, Web of Knowledge, China Biology Medicine, China National Knowledge Infrastructure, and ClinicalTrials.gov with no language restrictions. Eight clinical trials (252 participants) were selected from the 1121 identified studies and the relative phylum abundance extracted from the trials was analyzed using a random-effects model. Based on the analysis, anthocyanins had no effect on the relative abundance of Firmicutes (standard mean difference [SMD]: -0.46 [-1.25 to 0.34], P = .26), Proteobacteria (SMD, -0.32 [-0.73 to 0.09], P = .13), nor Actinobacteria (SMD, -0.19 [-0.50 to 0.12], P = 0.24), but influenced the abundance of Bacteroidetes (SMD, 0.84 [0.17 to 1.52], P = .01) when compared with placebo/control. No significant influence on the relative abundance was detected when the data were analyzed following the "posttreatment vs. pretreatment" strategy. Our preliminary analysis revealed that the effects of anthocyanins on human GI microbiota vary between studies and individuals, and at the current stage, the clinical trials regarding the effects of anthocyanin interventions on human GI microbiota are lacking. More trials with larger sample sizes are needed to promote the clinical application of anthocyanins.


Duration of palliative care before death in international routine practice: a systematic review and meta-analysis.
Early provision of palliative care, at least 3-4 months before death, can improve patient quality of life and reduce burdensome treatments and financial costs. However, there is wide variation in the duration of palliative care received before death reported across the research literature. This study aims to determine the duration of time from initiation of palliative care to death for adults receiving palliative care across the international literature. We conducted a systematic review and meta-analysis that was registered with PROSPERO (CRD42018094718). Six databases were searched for articles published between Jan 1, 2013, and Dec 31, 2018: MEDLINE, Embase, CINAHL, Global Health, Web of Science and The Cochrane Library, as well undertaking citation list searches. Following PRISMA guidelines, articles were screened using inclusion (any study design reporting duration from initiation to death in adults palliative care services) and exclusion (paediatric/non-English language studies, trials influencing the timing of palliative care) criteria. Quality appraisal was completed using Hawker's criteria and the main outcome was the duration of palliative care (median/mean days from initiation to death). One hundred sixty-nine studies from 23 countries were included, involving 11,996,479 patients. Prior to death, the median duration from initiation of palliative care to death was 18.9 days (IQR 0.1), weighted by the number of participants. Significant differences between duration were found by disease type (15 days for cancer vs 6 days for non-cancer conditions), service type (19 days for specialist palliative care unit, 20 days for community/home care, and 6 days for general hospital ward) and development index of countries (18.91 days for very high development vs 34 days for all other levels of development). Forty-three per cent of studies were rated as 'good' quality. Limitations include a preponderance of data from high-income countries, with unclear implications for low- and middle-income countries. Duration of palliative care is much shorter than the 3-4 months of input by a multidisciplinary team necessary in order for the full benefits of palliative care to be realised. Furthermore, the findings highlight inequity in access across patient, service and country characteristics. We welcome more consistent terminology and methodology in the assessment of duration of palliative care from all countries, alongside increased reporting from less-developed settings, to inform benchmarking, service evaluation and quality improvement.


Racemosins A and B, two novel bisindole alkaloids from the green alga Caulerpa racemosa.
Racemosin A (1), a structurally unique bisindole alkaloid possessing the seco-indolo[3,2-a]carbazole skeleton with two uncommon indolinenone units both conjugated with a methyl propenoate moiety, and its unusual cyclized derivative, racemosin B (2), were isolated from the green alga Caulerpa racemosa, together with the most commonly encountered pigment in the genus Caulerpa, caulerpin (3). Their structures were elucidated by extensive spectroscopic analysis and by comparison with data for related known compounds. A plausible biosynthetic pathway of 1 and 2 was proposed. In a neuro-protective assay, compound 1 significantly attenuated the Aβ2(5-35)-induced SH-SY5Y cell damage with a 14.6% increase in cell viability at the concentration of 10μM when compared to epigallocatechin gallate (EGCG, 16.57% increase at 10 μM) as the positive control.


Lateral decubitus chest radiography or chest ultrasound to predict pleural adhesions before medical thoracoscopy: a prospective study.
Medical thoracoscopy (MT) is the gold-standard to investigate unexplained pleural exudates. However, the major prerequisite is an easy pleural access obtained by creating an artificial pneumothorax at the beginning of the procedure which can be a challenge in case of pleural adhesions and make the procedure unsafe. The detection of pleural adhesions prior to MT is necessary. Nowadays chest ultrasonography (CUS) is considered the best procedure to detect pleural adhesions. However, this technique is not available in all countries where the assessment of the pleural cavity is only based on chest radiography. Therefore, we conducted this study to compare the performance of lateral decubitus chest radiography (LDCR) and CUS to predict pleural adhesions. LDCR and CUS were performed prior MT in consecutive patients presenting exudative pleural effusion to detect pleural adhesions. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for each pre thoracoscopy procedure were calculated. Data analysis for the sixty-six enrolled patients showed a higher superiority to detect pleural adhesions for CUS in comparison to LDCR for all the parameters analyzed. These results confirm that pre-MT CUS is the cornerstone to evaluate the access to the pleural cavity and justify educational program in this field in all centers which intends to develop interventional pulmonology.


Production of 11α-Hydroxysteroid Derivatives by Corynebacterium glutamicum Expressing the Rhizopus oryzae Hydroxylating System.
Hydroxylation of steroids has acquired special relevance for the pharmaceutical industry. Particularly, the 11α-hydroxylation of steroids is a process of biotechnological importance currently carried out at industrial scale for the production of contraceptive drugs and glucocorticoids. This process is performed by several fungal species including Rhizopus nigricans, Aspergillus ochraceus, Aspergillus niger, and Rhizopus oryzae that are used to produce by biotransformation hydroxylated steroids for pharmaceutical purposes (Wang et al., J Steroid Biochem Mol Biol 171:254-261, 2017). However, the development of more efficient biotransformation processes is essential since the steroidal derivatives obtained by the in vivo hydroxylation are often a mixture of hydroxylated compounds in different positions of the steroid molecule. This phenomenon is due to the large number of different CYPs contained in the fungal strains.The genes responsible for the 11α-hydroxylase activity in R. oryzae consisting in the cytochrome CYP509C12 and its redox partner, the reductase RoCPR1, have been chemically synthetized forming a synthetic operon named FUN optimized to be expressed in bacteria. To express this operon, we have selected the strain Corynebacterium glutamicum R31 that is a robust and GRAS bacterial strain widely used for industrial purposes. The synthetic operon has been cloned in the pECXK-99E vector, yielding pXKFUN plasmid, and transformed C. glutamicum R31 to generate C. glutamicum R31 (pXKFUN) strain. This strain is not a steroid degrader and can efficiently transport C19 and C21 steroids across the cytoplasmic membrane (García-Fernandez et al. Catalysts 316:1-12, 2017). C. glutamicum can be used as a clean host for steroid biotransformation, because it does not introduce additional undesired side reactions on the steroids, thus reducing the contamination of the final products (Felpeto-Santero et al., Microbiol Biotechnol 12:856-868, 2019). Here we show a proof of concept that C. glutamicum can be used as a suitable chassis to perform steroid biotransformation expressing eukaryotic cytochromes. The protocol below provides detailed information on steroid 11α-hydroxylations by Corynebacterium recombinant strain.


Quantitative evaluation of the bone-metal interface in implants with two different surface roughnesses: an experimental study in rabbits.
Direct bone-metal contact is considered the ideal condition in order to obtain stability of orthopaedic non cemented implants. To acheive this result various implant shapes and surfaces were proposed.


Supermarket discounts of low-energy density foods: effects on purchasing, food intake, and body weight.
To assess the effects of a 50% discount on low-energy density (ED) fruits and vegetables (F&V), bottled water, and diet sodas on shoppers' purchasing, food intake, and body weight. A randomized, controlled trial was conducted at two Manhattan supermarkets, in which a 4-week baseline period (no discounts) preceded an 8-week intervention period (50% discount), and a 4-week follow-up period (no discounts). Twenty-four hour dietary recall, as well as body weight and body composition measures were obtained every 4 weeks. Participants (n = 47, 33f; 14m) were overweight and obese (BMI ≥ 25) shoppers. Purchasing of F&V during intervention was greater in the discount group than in the control group (P < 0.0001). Purchasing of these items by the discount group relative to the control group during follow-up was reduced from intervention (P = 0.002), but still remained higher than during baseline (P = 0.01), indicating a partially sustained effect. Intake of F&V increased from baseline to intervention in the discount group relative to the control group (P = 0.037) and was sustained during follow-up. Body weight change did not differ significantly between groups, although post hoc analysis indicated a change within the discount group (-1.1 kg, P = 0.006) but not within the control group. Discounts of low-ED F&V led to increased purchasing and intake of those foods.


Cooperative inhibitory effects of uremic toxins and other serum components on OATP1B1-mediated transport of SN-38.
Half-life of SN-38, an active metabolite of irinotecan, remarkably increases in patients with end-stage kidney disease (ESKD), even though SN-38 is excreted in bile. Uremic toxins (UTs), which accumulate in the serum of ESKD patients, were reported to inhibit organic anion-transporting polypeptide (OATP) 1B1-mediated uptake of SN-38; however, the relevance of this finding in a clinical setting is unknown. This study focused on cooperative effects of serum components and UTs on OATP1B1-mediated transport of SN-38. Uptake of SN-38 by OATP1B1 was evaluated using cells stably expressing OATP1B1. Serum was obtained from > 400 ESKD patients undergoing hemodialysis. Deproteinized serum was combined with human serum albumin (HSA) to explore the effects of albumin-bound and unbound serum compounds. Uptake clearance of SN-38 in OATP1B1 cells decreased by 40% in the presence of uremic serum residue with albumin compared to that in the presence of normal serum residue. Additional UTs (3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, hippuric acid, indole-3-acetic acid, and 3-indoxyl sulfate) combined with normal serum residue in HSA decreased OATP1B1-mediated SN-38 transport by 32.1% compared to that in the presence of normal serum residue. The inhibitory effect of albumin-unbound fraction with UTs and normal serum residue was comparable to that of uremic serum residue, with an uptake decrease of 17.2% compared to that reported in the presence of normal serum residue. Hepatic uptake of SN-38 via OATP1B1 decreases in ESKD patients through cooperative inhibitory effects of UTs and serum components.


Treatment of Canine Disc-Associated Cervical Spondylomyelopathy with a Cervical Distraction-Stabilization Technique (C-LOX Combined with LCP Plate) and Clinical Outcomes.
Canine disc-associated cervical spondylomyelopathy (DA-CSM) is a form of caudal CSM, characterized by the compression of the spinal cord and nerve roots due to an intervertebral disc protrusion. It is more frequent in large canine breeds. A variety of surgical techniques has been proposed for DA-CSM. The aim of the study was to evaluate the outcomes of a cervical distraction-stabilization technique using an intervertebral anchored fusion device (C-LOX) combined with a locking compression plate (LCP plate) for the treatment of DA-CSM in dogs, based on clinical and radiographical follow-up data. Thirteen dogs affected by DA-CSM were included in the study. After the surgical procedure, an improvement in neurological status was documented in 9/13 cases. This cervical distraction-stabilization technique seems to be a valuable surgical alternative to treat this canine pathology.


Role of nitric oxide in non-adrenergic, non-cholinergic inhibitory junction potentials in canine ileocolonic sphincter.
1. Electrical field stimulation causes neurally-mediated relaxation of the ileocolonic sphincter that is due to activation of non-adrenergic and non-cholinergic (NANC) nerves. Recent studies have suggested that nitric oxide (NO) is the neurotransmitter that mediates relaxation. 2. Using intracellular recording techniques, we have tested whether NANC inhibitory junction potentials (i.j.ps) in the canine ileocolonic sphincter are also mediated by NO. 3. Electrical field stimulation elicited excitatory and inhibitory junction potentials: e.j.ps were blocked by atropine (10(-6) M) and tetrodotoxin (TTX; 10(-6) M); i.j.ps were also blocked by TTX and partially blocked by apamin (10(-6) M). I.j.ps were unaffected by atropine, phentolamine and propranolol (all at 10(-6) M). 4. The arginine analogues, L-NG-nitroarginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), decreased the amplitude of i.j.ps and L-arginine, but not D-arginine, partially restored the i.j.ps. 5. I.j.ps were also inhibited by oxyhaemoglobin (1%), but not by methaemoglobin. 6. Exogenous NO (10(-7) M to 3 x 10(-5) M) caused concentration-dependent hyperpolarizations that were similar in amplitude to the NANC nerve-evoked i.j.ps. Hyperpolarizations to NO were unaffected by L-NAME, but were blocked by oxyhaemoglobin. 7. Tetrodotoxin, L-NAME and oxyhaemoglobin all caused depolarization of resting membrane potential. 8. The specific guanosine 3':5'-cyclic monophosphate phosphodiesterase inhibitor, M&B 22948, caused hyperpolarization, increased the maximum level of hyperpolarization reached during i.j.ps, and increased the duration of i.j.ps. 9. These data further support the hypothesis that NANC neurotransmission in the ileocolonic sphincter is mediated by NO or an NO-releasing compound. The data also suggest that tonic release of NO, possibly from spontaneous firing of NANC nerves, may regulate resting membrane potential and tone in this sphincter.


In vivo programming of endogenous antibodies via oral administration of adaptor ligands.
Vaccination is a reliable method of prophylaxis and a crucial measure for public health. However, the majority of vaccines cannot be administered orally due to their degradation in the harsh gut environment or inability to cross the GI tract. In this study, we report the first proof-of-concept study of orally producible chemically programmed antibodies via specific conjugation of adaptor ligands to endogenous antibodies, in vivo. Pre-immuniztion with 2,4-dinitrophenyl (DNP), or the reactive hapten, 1,3-diketone (DK), or a novel reactive hapten, vinyl sulfone (VS) in mice, followed by oral administration of adaptor ligands composed of the hapten and biotin to the pre-immunized mice resulted in successful in vivo formation of the biotin-hapten-antibody complexes within 2h. Pharmacokinetic evaluations revealed that apparent serum concentrations of programmed antibodies were up to 144nM and that the serum half-lives reached up to 34.4h. These findings show promise for the future development of orally bioavailable drug-hapten-antibody complexes asa strategy to quickly and easily modulate immune targets for aggressive pathogens as well as cancer.


Simulating Four Essential Conversations with Hematology/Oncology Trainees: a Qualitative Evaluation.
Hematologists/oncologists have a crucial responsibility to effectively communicate with patients. However, they have been criticized for ineffective communication with patients. To develop effective communication behaviors that meet the needs of patients and families, trainees need practice and feedback about their performance. Medical faculties frequently teach communication skills using simulation-based curricula; however, they often include only general communication skills, without tailored approaches for specialties. This study examined Hematology/Oncology trainees' qualitative perceptions about the value of and techniques used for simulations of specialty specific, essential conversations with patients and families, and debriefing sessions. Results demonstrate a highly effective curriculum and positive learner experiences. While most reports on this topic take place within major academic cancer centers, outcomes from a mid-sized Hematology/Oncology training program are unknown. The study confirms feasibility for implementing a simulation-based communications program in a mid-sized Hematology/Oncology program and describes simulation techniques that were effective.


Infective complications of cosmetic tourism: A systematic literature review.
Cosmetic tourism has increased dramatically over the years. We performed a systematic review of the literature to find reports of infective complications following cosmetic surgery, focusing on epidemiology, clinical, and surgical management. In addition, we identified cosmetic tourism trends in terms of mobilization from the country of origin and travel destinations. A search on PubMed, Embase, and Web of Science was performed between March and August 2022. The search was not restricted based on study date. Only English manuscripts were assessed. Reviews, short communications, letters, and correspondences were excluded after reviewing their references for potentially relevant studies. Articles related to non-cosmetic surgeries were also excluded from the study. We identified 152 articles, of which 31 were duplicates and 47 were excluded based on title/abstract assessment. Three non-English manuscripts, 13 reviews, 12 letters to the editor, and 10 articles that did not feature clinical cases were also rejected. Thirty-six articles were included for analysis. We found 370 patients with infective complications following cosmetic surgery. The severity of complications was stratified according to the Clavien-Dindo classification. Most reports were from the United States (56.5%), followed by Switzerland and the United Kingdom. Travel destinations included the Dominican Republic (34.3%), Turkey, and Colombia. Infective complications commonly occurred after abdominoplasties in patients who underwent cosmetic surgeries in Latin America or Asia. Most infective complications required management with surgical procedures that involved the administration of local, regional, or general anesthesia. Gluteal augmentations were the fourth most common cosmetic procedures; however, they were associated with the highest number of severe cases, which required intensive care treatment.


Lipoprotein particles in the jejunal mucosa of postnatal developing rats.
The jejunal mucosa of neonatal rats contains lipid particles of the same size, electron density and intracellular and extracellular distribution as particles identified by others in adult jejunum as lipoprotein particles. As in fetal jejunum obtained during the last three days of gestation, the jejunal mucosa of unsuckled newborn rats contains exclusively lipoprotein particles the size of very low density lipoproteins (VLDL). Within one day after initiation of suckling, there is in the mucosa a spectrum of lipoprotein particles ranging widely in size from those of VLDL particles to those of chylomicrons. These particles are seen in the endoplasmic reticulum and Golgi material of absorptive cells and within interepithelial cell spaces, the extracellular spaces of the lamina propria and lymphatic lacteals. VLDL-sized and chylomicron-sized particles are also seen, although in decreasing number, in the jejunal mucosa of 18-day-old suckling rats. However, in rats of comparable age, fasted for 48 or 72 hours, only VLDL-sized particles are seen in the jejunal mucosa. Ligation and transection of bile duct followed by fasting in rats of this age results in a marked decrease in the number of lipoprotein particles in absorptive cells. The results indicate that endogenous lipid contributes to the formation of VLDL particles whereas dietary triglycerides are needed for formation of chylomicrons.


Giant posterolateral left ventricular aneurysm diagnosed 6 weeks after incomplete surgical revascularization.
We report the surgical repair of a true left ventricular aneurysm diagnosed 6 weeks after incomplete surgical revascularization.


2,5-Hexanedione alters microtubule assembly. I. Testicular atrophy, not nervous system toxicity, correlates with enhanced tubulin polymerization.
Charles River CD rats (200 g) were divided into three groups receiving either 1% 2,5-hexanedione (2,5-HD) or 0.035% 3,4-dimethyl-2,5-hexanedione (DMHD) in the drinking water or water alone (control) for 4 weeks. The two treated groups experienced similar nervous system dysfunction and systemic toxicity. Testicular toxicity, as evidenced by histological changes and decreased testis weight, was present only in 2,5-HD-treated rats. Tubulin was purified from brain and testis and assembly properties were determined. Purified brain and testis tubulin derived from the 2,5-HD-intoxicated rats displayed altered assembly with a shortened nucleation phase and more rapid rate of elongation. Brain tubulin from DMHD-intoxicated rats displayed assembly behavior similar to controls, while testis tubulin from DMHD-intoxicated rats displayed assembly behavior intermediate between the control and 2,5-HD tubulin preparations. The presence of gamma-diketone-induced assembly alterations following in vivo intoxication was accompanied by the formation of a high-molecular-weight protein identified as crosslinked tubulin. From these data, we conclude that microtubule assembly alterations are not etiologic in the development of nervous system dysfunction following intoxication but may represent the biochemical mechanism of 2,5-HD-induced testicular atrophy.


Decrease in LDL and increase in HDL concentrations in type II hyperlipoproteinaemic patients on low-dose combination therapy of cholestyramine and Complamin.
A low-dose combination of Complamin retard (1 g t.i.d.) and cholestyramine (4 g b.i.d.) was compared with each agent alone in 2 serial open trials without dietary restriction using type IIa and IIb hyperlipoproteinaemic patients. Complamin alone produced decreases in LDL and VLDL cholesterol concentrations (up to 20%) whereas cholestyramine alone produced only a modest reduction in LDL (up to 15%). The combination produced marked, progressive reductions in total cholesterol (up to 35%) and LDL (up to 40%); reductions in VLDL (up to 45%), total triglyceride (up to 60%) and free fatty acids (up to 60%) were found only in type IIb patients. The average increase in HDL-cholesterol from the 2 studies for combination therapy was 35%. No side-effects were reported or measured and compliance was excellent. The results demonstrate the potential of a method of achieving beneficial actions on lipoprotein levels with a well-tolerated therapy.


Healthcare Cost of Over-Diagnosis of Low-Grade Dysplasia in Barrett's Esophagus.
Published reports have demonstrated that many Barrett's esophagus patients are over-diagnosed as low-grade dysplasia (BE-LGD). We performed an analysis of the surveillance and treatment costs associated with the over-diagnosis of BE-LGD. As the principal cost variables, we used endoscopic and histologic procedures performed during the recommended surveillance intervals for patients with BE-LGD, the national average Medicare reimbursement for the Current Procedural Terminology codes of the procedures performed, and a spreadsheet-based tool we created to determine the overall healthcare cost associated with the over-diagnosis of BE-LGD in the US population. The average excess cost (range) for every patient in the US who is over-diagnosed with BE-LGD is estimated to be $5557 ($3115 to $8072). The principal contributors to the excess cost of over-diagnosis of BE-LGD in these patients are: endoscopy ($2626 to $4639), pathologist biopsy review ($275 to $2185), and esophagogastroduodenoscopy-guided endoscopic ablation ($214 to $1249). The healthcare cost of over-diagnosis of BE-LGD is significant. To reduce the overall healthcare cost impact of over-diagnosis of BE-LGD, strict adherence to the recommendations of the American Gastroenterological Association, American College of Gastroenterology, and American Society for Gastrointestinal Endoscopy that pathology review of all BE biopsy specimens be performed by a gastrointestinal pathologist is warranted.


31P NMR characterization of cellular metabolism during dexamethasone induced apoptosis in human leukemic cell lines.
31P NMR has been used to study the effects of dexamethasone on phosphorus metabolism in one dexamethasone (dex)-sensitive (CEM-C7) and three different dex-resistant (CEM-C1, CEM-4R4, and CEM-ICR27) human leukemic cell lines. The use of these cell lines, containing widely varying amounts of glucocorticoid receptors, made it possible to evaluate the receptor-mediated contributions to the modes of action of dexamethasone in these cells. To evaluate the effects of dexamethasone without any significant contribution from experimental conditions, all the experiments were done with parallel controls. Results obtained showed: 1) significantly different levels of phosphorylethanolamine (PE) and phosphorylcholine (PC) among cell lines, suggesting significant differences in phospholipid metabolism; 2) the dexamethasone induced reduction of phosphomonoester (PE+PC), ATP, and metabolic rates probably through glucocorticoid receptor mediated mechanisms; 3) the dexamethasone induced stimulation of cellular metabolism in a process which seems to be independent of glucocorticoid receptors; and 4) the dexamethasone induced alkaline shift of intracellular pH in all the cell lines except ICR27. The reduction in PME levels seems to be an earlier step in dexamethasone-induced apoptosis than the reduction in ATP. The degree of alkaline shift was found to correlate with the number of glucocorticoid receptors present. The possible involvement of phospholipid metabolites as second messengers in dexamethasone-induced apoptosis is discussed.


SBP ratio in exercise stress testing: validation by perfusion imaging.
The 3-min SBP ratio (SBPR) was proposed to detect significant coronary artery disease (CAD), but its relationship with abnormalities detected by myocardial perfusion-gated single-photon emission computed tomography (SPECT) was never examined. In 156 consecutive patients submitted to resting and exercise gated SPECT for suspect CAD, perfusion scores, ejection fraction and transient ischemic dilatation (TID) were evaluated and compared with SBPR. There were weak correlations between SBPR and summed stress score (ρ = 0.232, P < 0.004), and summed difference score (SDS) (ρ = 0.228, P < 0.004). According to receiver operating characteristic analysis, SBPR was poorly effective for identifying patients with inducible ischemia (SDS ≥ 2): area under curve = 0.64, (P < 0.002), sensitivity = 82%, specificity = 40%. No relationship was registered between SBPR and postexercise ejection fraction drop, and the relationship with TID was poor (ρ = 0.263, P < 0.001). In patients submitted to gated SPECT for suspect CAD, SBPR appears poorly effective for the detection of significant CAD, and does not show any valuable relationship with exercise-induced functional abnormalities.


A mixture of anatase and rutile TiO₂ nanoparticles induces histamine secretion in mast cells.
Histamine released from mast cells, through complex interactions involving the binding of IgE to FcεRI receptors and the subsequent intracellular Ca²⁺ signaling, can mediate many allergic/inflammatory responses. The possibility of titanium dioxide nanoparticles (TiO₂ NPs), a nanomaterial pervasively used in nanotechnology and pharmaceutical industries, to directly induce histamine secretion without prior allergen sensitization has remained uncertain. TiO₂ NP exposure increased both histamine secretion and cytosolic Ca²⁺ concentration ([Ca²⁺]C) in a dose dependent manner in rat RBL-2H3 mast cells. The increase in intracellular Ca²⁺ levels resulted primarily from an extracellular Ca²⁺ influx via membrane L-type Ca²⁺ channels. Unspecific Ca²⁺ entry via TiO₂ NP-instigated membrane disruption was demonstrated with the intracellular leakage of a fluorescent calcein dye. Oxidative stress induced by TiO₂ NPs also contributed to cytosolic Ca²⁺ signaling. The PLC-IP₃-IP₃ receptor pathways and endoplasmic reticulum (ER) were responsible for the sustained elevation of [Ca²⁺]C and histamine secretion. Our data suggests that systemic circulation of NPs may prompt histamine release at different locales causing abnormal inflammatory diseases. This study provides a novel mechanistic link between environmental TiO₂ NP exposure and allergen-independent histamine release that can exacerbate manifestations of multiple allergic responses.


The interaction of nitric oxide with soybean lipoxygenase-1.
The interaction of nitric oxide with the non-heme iron dioxygenase lipoxygenase is reported. This apparently resulted in a novel type of complex where an electron is donated to the NO molecule. In addition a new position for an EPR transition from iron was discovered which, it is suggested results from high spin ferric iron in a field of axial symmetry characterised by a very low value for D.


Expression and regulation of osteoprotegerin in adipose tissue.
Osteoprotegerin (OPG), a potent inhibitor of osteoclastic bone resorption, has a variety of biological functions that include anti-inflammatory effects. Adipocytes and osteoblasts share a common origin, and the formation of new blood vessels often precedes adipogenesis in developing adipose tissue microvasculature. We examined whether OPG is secreted from adipocytes, therefore contributing to the prevention of neovascularization and protecting the vessels from intimal inflammation and medial calcification. The mRNA expression of OPG and receptor activator of NF-kappaB ligand (RANKL) was measured in differentiated 3T3L1 adipocytes and adipose tissues. OPG mRNA expression increased with the differentiation of 3T3L1 adipocytes, while RANKL expression was not significantly altered. OPG mRNA was expressed at higher levels in white adipose tissue than in brown adipose tissue and was most abundant in the epididymal portion. In differentiated 3T3L1 adipocytes, Rosiglitazone and insulin reduced the OPG/RANKL expression ratio in a dose- and time- dependent manner. In contrast, tumor necrosis factor-alpha (TNF-alpha) increased the expression of both OPG and RANKL in a time-dependent manner. The OPG/RANKL ratio was at a maximum two hours after TNF-alpha treatment and then returned to control levels. Furthermore, OPG was abundantly secreted into the media after transfection of OPG cDNA with Phi C31 integrase into 3T3L1 cells. Our results indicate that OPG mRNA is expressed and regulated in the adipose tissue. Considering the role of OPG in obesity-associated inflammatory changes in adipose tissue and vessels, we speculate that OPG may have both a protective function against inflammation and anti-angiogenic effects on adipose tissue.


Application of a PCR protocol for the diagnosis of trichothecene producingFusarium species in deoxynivalenol contaminated wheat.
Trichothecenes pose a health risk to consumers and the presence of the producing fungi causes problems in industrial processing of cereals. A Triplex PCR was developed for screening of samples contaminated with toxigenic Fusarium species. The Triplex PCR could detect Fusarium species with high precision as compared to microbiological data of sample materials. There was a positive correlation between the occurrence of a PCR signal and the prevalence of the mycotoxin DON (Deoxynivalenol).


Red blood cell exchange in patients with sickle cell disease-indications and management: a review and consensus report by the therapeutic apheresis subsection of the AABB.
A prior practice survey revealed variations in the management of patients with sickle cell disease (SCD) and stressed the need for comprehensive guidelines. Here we discuss: 1) common indications for red blood cell exchange (RCE), 2) options for access, 3) how to prepare the red blood cells (RBCs) to be used for RCE, 4) target hemoglobin (Hb) and/or hematocrit (Hct) and HbS level, 5) RBC depletion/RCE, and 6) some complications that may ensue. Fifteen physicians actively practicing apheresis from 14 institutions representing different areas within the United States discussed how they manage RCE for patients with SCD. Simple transfusion is recommended to treat symptomatic anemia with Hb level of less than 9 g/dL. RCE is indicated to prevent or treat complications arising from the presence of HbS. The most important goals are reduction of HbS while also preventing hyperviscosity. The usual goals are a target HbS level of not more than 30% and Hct level of less than 30%. Although a consensus as to protocol details may not be possible, there are areas of agreement in the management of these patients, for example, that it is optimal to avoid hyperviscosity and iron overload, that a target Hb S level in the range of 30% is generally desirable, and that RCE as an acute treatment for pain crisis in the absence of other acute or chronic conditions is ordinarily discouraged.


The effect of subthalamic deep brain stimulation on gastric motility in Parkinson's disease.
Deep brain stimulation of the subthalamic nucleus (STN-DBS) is well established for treating the motor symptoms for advanced Parkinson's disease (PD) but its effects on gastric myoelectrical activity and gastrointestinal symptoms have not been well studied. The aim of this study was to evaluate the effect of STN-DBS on gastric motility using electrogastrography (EGG). Twenty patients with PD (5 females, 15 males; mean aged 58.0 ± 9.0 years) who underwent STN-DBS were studied. EGG was performed in fasting and postprandial conditions before STN-DBS and 3 months after the surgery. We also evaluated the frequency and severity of gastrointestinal symptoms based on a structured gastrointestinal dysfunction questionnaire. After STN-DBS the percentage of normogastria (47.8 ± 20.7 vs 51.3 ± 15.1) and period dominant power (PDP) (11.8 ± 1.2 vs 12.3 ± 0.9) significantly increased, the percentage of arrhythmia decreased compared to the baseline during fasting and postprandial state. Abnormal response to a meal (power ratio of PDP <1 after meal) decreased from 70% to 55% after 3 months follow-up. The abnormal EGG (the percentage of normogastria <70%) decreased in both fasting (from 80% to 65% patients) and postprandial state (from 80% to 60% patients), respectively after the surgery. The most common GI symptoms reported prior to the surgery were constipation 95%, difficulty with defecation 85% and dysphagia 50%. After STN-DBS all gastrointestinal symptoms improved, the greatest improvement was observed in difficulty with defecation. Our results suggest that STN-DBS improves gastric motility as well as gastrointestinal symptoms in PD. Further studies of gastrointestinal motility in PD are warranted.


Diversity and Bioactivity of Endophytic Actinobacteria Associated with Grapevines.
Grapevine trunk diseases (GTDs) are a significant problem for New Zealand viticulture. Endophytic actinobacteria are of interest as potential biocontrol agents due to their ability to inhibit plant pathogens and improve plant growth. However, no studies have investigated the diversity of actinobacteria associated with grapevines in New Zealand vineyards and their bioactivity. Actinobacteria diversity in different 'Sauvignon blanc' vine tissues from three vineyards (conventional and organic management, and different vine ages) was assessed using different methods and media. Forty-six endophytic actinobacteria were isolated, with more isolates recovered from roots (n = 45) than leaves (n = 1) and shoot internodes (n = 0). More isolates were recovered from the organic (n = 21) than conventional (n = 8) vineyard, mature (25-year old; n = 21) than young (2-year old; n = 2) vines and using a tissue maceration technique (n = 40). Actinomycete Isolation Agar, International Streptomyces Project 2, and Starch Casein media were effective for actinobacteria isolation. Most of the isolates recovered belonged to Streptomyces, with one isolate identified as Mycolicibacterium. Forty isolates were assessed for antifungal activity and plant growth-promoting (PGP) characteristics. Of these, 13 isolates had antifungal activity against test GTD pathogens (Dactylonectria macrodidyma, Eutypa lata, Ilyonectria liriodendri, Neofusicoccum parvum, and N. luteum). Eighteen isolates exhibited more than one PGP trait; 25siderophore production (n = 25), phosphate solubilization (n = 6), and indole acetic acid production (n = 16). Two strains, Streptomyces sp. LUVPK-22 and Streptomyces sp. LUVPK-30, exhibited the best antifungal and PGP properties. This study revealed the diversity of culturable endophytic actinobacteria from grapevines in New Zealand vineyards and their biocontrol potential against GTD pathogens.


Glial Heterotopia of the Middle Ear: First Case in Indian Literature.
A 66-years-old female presented with impaired hearing of two-year duration and a recent ear discharge. High-resolution computed tomography and intra-operative findings showed a mass lesion in the right middle ear cavity that was unconnected with the brain. A histopathological diagnosis of glial heterotopia was made and an etiopathogenic hypothesis was analysed.


Effect of limited aeration on the anaerobic treatment of evaporator condensate from a sulfite pulp mill.
Serious inhibition was found in the regular up-flow anaerobic sludge blanket (UASB) reactor in treating the evaporator condensate from a sulfite pulp mill, which contained high strength sulfur compounds. After applying the direct limited aeration in the UASB, the inhibition was alleviated gradually and the activity of the microorganisms was recovered. The COD removal rate increased from 40% to 80% at the organic loading rate of 8kgCODm(-3)d(-1) and a hydraulic retention time of 12h. Limited aeration caused no oxygen inhibition to the anaerobic microorganisms but instigated sulfide oxidization and H(2)S removal, which was beneficial to the methanogens. The experiment confirmed the feasibility of applying limited aeration in the anaerobic reactor to alleviate the sulfide inhibition. It also proved that the anaerobic system was actually aerotolerant. SEM observation showed that the predominant microorganisms partly changed from rod-shaped methanogens to cocci after the UASB reactor was aerated.


Health status and comorbidities of adult patients with phenylketonuria (PKU) in France with a focus on early-diagnosed patients - A nationwide study of health insurance claims data.
This study aimed at evaluating the health status and healthcare consumption of ≥16-year-old patients with phenylketonuria (PKU), with a focus on early-diagnosed patients. This retrospective observational study used health insurance claims data from the French SNDS (Système National des Données de Santé) database. Patients with PKU were identified between 2006 and 2018 by ICD-10 diagnosis codes E70.0 (classic PKU) or E70.1 (other causes of hyperphenylalaninemia). They were matched to controls by age, sex, and region. Patients with early-diagnosed PKU were defined as patients born after implementation of nationwide newborn screening in France in 1972. Outcomes were analyzed for the year 2018. Overall, 3549 patients with PKU were identified on January 1st, 2018. Of those, 3469 patients could be matched to 17,170 controls without PKU. Of these patients, 2175 were at least 16 years old and suffered significantly more than controls from specific comorbidities of interest - osteoporosis (28.7% vs 19.8%, p < 0.0001), hypertension (20.9% vs 17.0%, p < 0.0001), hypercholesterolemia (12.8% vs 8.3%, p < 0.0001), diabetes (7.8% vs 4.7%, p < 0.0001), obesity (4.2% vs 1.3%, p < 0.0001), ischemic heart diseases (4.8% vs 2.0%, p < 0.0001), and depression (10.3% vs 8.2%, p = 0.0011). Prescriptions for many medications were also more frequent in patients with PKU than controls. Among ≥16-year-old patients, 1528 were categorized as early-diagnosed. Osteoporosis (0.3% vs 0.01%, p = 0.0035), chronic renal failure (0.6% vs 0.1%, p = 0.0020), hypertension (4.0% vs 2.7%, p = 0.0063), and obesity (2.5% vs 0.8%, p < 0.0001) were significantly more prevalent in early-diagnosed adult patients compared with matched controls. In total, 28.6% of ≥16-year-old patients with PKU and 40.4% of early-diagnosed patients with PKU received dietary amino-acid supplements. Sapropterin was prescribed to 5.0% and 7.0% patients, respectively. The results indicate that PKU is associated with a significantly higher comorbidity risk along with increased pharmaceutical prescriptions in adulthood. The comorbidity burden is less distinct in early-diagnosed patients but still present. Few patients are treated specifically for PKU in adulthood. Healthcare of patients with PKU should include prevention and management of comorbidities and especially target PKU-specific treatment adherence and consistent care in specialized medical centers in adulthood.


Circulating tumor DNA as a prognostic indicator of colorectal cancer recurrence-a systematic review and meta-analysis.
Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. After resection, patients need extensive follow-up to detect asymptomatic recurrences as early as possible to obtain optimal treatment. This study evaluated the prognostic value of circulating tumor DNA (ctDNA) for CRC recurrence. Two investigators independently conducted a systematic literature search of peer-reviewed studies that investigated the prognostic value of ctDNA in CRC. Fixed effects or random effects models were applied for all analyses based on the assessment of heterogeneity. A total of 189 studies were initially retrieved from all databases; ultimately, eight studies with 879 CRC patients were included in this analysis. The pooled median recurrence-free survival was 11.36 months for ctDNA-positive patients. Meta-analysis of hazard ratio (HR) suggested that postoperative ctDNA-positive patients were more likely to experience cancer recurrence than ctDNA-negative patients (pooled HR: 5.41; 95% confidence interval (CI): 2.37-8.45). Successive monitoring of ctDNA status and follow-up with postoperative computed tomography (CT)/magnetic resonance imaging (MRI) are useful tools to detect early recurrence in postoperative ctDNA-positive patients.


Can a determination of tartrate-resistant acid phosphatase predict postmenopausal loss of bone mass?
A study was carried out over a 24-month interval to determine if an initial measurement of serum tartrate-resistant acid phosphatase would be predictive of bone mass loss quantified by dual-energy X-ray absorptiometry, as total bone mineral content and total bone mineral content corrected for weight. Sixty-two women were studied (at onset: mean age 59.7 +/- 8.9 years, 10.8 +/- 8.8 years since menopause; at conclusion: mean age 61.9 +/- 8.8 and 13.0 +/- 8.7 since menopause). A paired Wilcoxon test showed a small, but significant, increase in weight (P < 0.05) and decrease in height (P < 0.05). Total bone mineral content and total bone mineral content corrected for weight decreased (P < 0.005 and 0.0001, respectively). Serum tartrate-resistant acid phosphatase increased (P < 0.005). Single-regression analysis showed that the per cent bone mass loss observed between the first and second body bone mineral content measurements correlated negatively with the first serum tartrate-resistant acid phosphatase determination (r = -0.62, P < 0.0001). Changes in tartrate-resistant acid phosphatase correlated negatively with changes in total bone mineral content (r = -0.79, P < 0.0001). In a multiple regression analysis of per cent change in bone mass against initially important variables such as age, years since menopause, weight, and tartrate-resistant acid phosphatase, only tartrate-resistant acid phosphatase was significant (P < 0.0001). The sensitivity and specifity of tartrate-resistant acid phosphatase for evaluating bone loss were 86% and 78%, respectively, and the area under the curve was of 0.83 (95% CI 0.71-0.95). These results show that a simple measurement of serum tartrate-resistant acid phosphatase can help to predict the potential rate of bone mass loss in women.


Laser in situ keratomileusis in a patient with congenital nystagmus.
We report the results of laser in situ keratomileusis (LASIK) to correct myopia in a 47-year-old woman with congenital motor nystagmus and myopia. The patient had simultaneous bilateral LASIK using the Alcon-Summit-Autonomous LADARVision excimer laser. Her uncorrected visual acuity (UCVA) preoperatively was 20/600 in the right eye and 20/800 in the left eye; best corrected visual acuity was 20/40 in both eyes. Twelve months after bilateral LASIK, with an enhancement procedure in both eyes at 4 months, UCVA was 20/40 in both eyes. Corneal topography showed well-centered ablation zones.


Effects of alterations in arterial pressure and heart rate on ST-segment elevation in a patient with acute myocardial infarction.
This report describes a 70-year-old male with an anterior transmural myocardial infarction who showed major alterations in the magnitude of ST-segment elevation of his electrocardiogram, when an abrupt change of his heart rate (reduction) and blood pressure (increase) occurred when he reverted to normal sinus rhythm from atrial fibrillation. No concomitant change of other parameters of his clinical status was observed. This report stresses the significance of monitoring serially blood pressure, heart rate, and clinical symptomatology, in addition to electrocardiographic ST-segment elevations in patients with myocardial infarction, when therapeutic interventions aimed at reducing the infarct size are evaluated.


A new side-effect of sufentanil: increased monocyte-endothelial adhesion.
Opioids have been identified by the World Health Organization to be 'indispensable for the relief of pain and suffering'. Side-effects, such as nausea, vomiting, postoperative delirium, and effects on breathing, of opioids have been well investigated; however, the influence of opioids on monocyte-endothelial adherence has never been reported. Therefore, we explored the effects of representative opioids, fentanyl, sufentanil, and remifentanil, on monocyte-endothelial adherence and the underlying mechanisms. We built a cell adhesion model with U937 monocytes and human umbilical vein endothelial cells (HUVECs). Two kinds of connexin43 (Cx43) channel inhibitors, 18-α-GA and Gap 27, were used to alter Cx43 channel function in U937 monocytes and HUVECs, respectively, to determine the effects of Cx43 channels on U937-HUVEC adhesion. Subsequently, the effects of fentanyl, sufentanil and remifentanil on Cx43 channel function and U937-HUVEC adhesion were explored. When fentanyl, sufentanil and remifentanil acted on monocytes or endothelial cells, their effects on monocyte-endothelial adherence differed. When acting on U937 monocytes, sufentanil significantly increased U937-HUVEC adhesion which was associated with reduced release of ATP from Cx43 channels, while fentanyl and remifentanil did not have these influences. Although sufentanil could also inhibit Cx43 channel function in HUVECs, it had no effect on ATP release from HUVECs or U937-HUVECs adhesion. We demonstrated that sufentanil application increases monocyte-endothelial adherence which was associated with reduced release of ATP from Cx43 channels in monocytes. This side-effect of sufentanil should be considered seriously by clinicians.


A cigarette pack by any other color: Youth perceptions mostly align with tobacco industry-ascribed meanings.
•Youth interpret cigarette pack-colors in line with industry-intended associations.•Product-packaging restrictions may be circumvented by use of colors that misrepresent product harms.•43.2% of participants attributed extra strong to the black cigarette pack.•35.6% of participants ascribed rich to gold.•31.1% of participants ascribed menthol to green.


No association between ApoE and schizophrenia: Evidence of systematic review and updated meta-analysis.
Schizophrenia affects between 0.3% and 2% of the worldwide population. A genetic contribution has been postulated in the development of this disorder. Genes such as ApoE have been implicated in the neurodevelopment associated with schizophrenia in case-control and meta-analysis studies, but the results remain inconclusive. Due to this, the aim of the present study was to explore the association between ApoE and schizophrenia through a meta-analysis. We collected all relevant studies by searching PubMed and EBSCO databases. The pooled odds ratios with 95% confidence intervals were calculated to estimate the association. The following models were evaluated: A) ε4 vs ε3, B) ε4 vs ε2, C) ε4 vs ε3+ε2, D) Caucasian population and E) Asian population. Statistical analyses were performed using EPIDAT 3.1 software. The meta-analyses comprised 28 association studies, which included 4703 controls and 3452 subjects with schizophrenia. A significant protective effect was found for allele ε3 in the Asian population (OR=0.73, 95% CI=0.54-0.98). No significant associations were observed in the other models and populations analyzed. Our meta-analysis suggests a protective association between ApoE allele ε3 and schizophrenia in the Asian population.


PsiB, and anti-SOS protein, is transiently expressed by the F sex factor during its transmission to an Escherichia coli K-12 recipient.
PsiB, an anti-SOS protein, shown previously to prevent activation of RecA protein, was purified from the crude extract of PsiB overproducing cells. PsiB is probably a tetrameric protein, whose subunit has a sequence-deduced molecular mass of 15741 daltons. Using an immuno-assay with anti-PsiB antibodies, we have monitored PsiB cell concentrations produced by F and R6-5 plasmids: the latter type produces a detectable level of PsiB protein while the former does not. The discrepancy can be assigned to a Tn10 out-going promoter located upstream of psiB. When we inserted a Tn10 promoter upstream of F psiB, the F PsiB protein concentration reached the level of R6-5 PsiB. We describe here the physiological role that PsiB protein may have in the cell and how it causes an anti-SOS function. We observed that PsiB protein was transiently expressed by a wild-type F sex factor during its transmission to an Escherichia coli K-12 recipient. In an F+ x F- cross, PsiB concentration increased at least 10-fold in F- recipient bacteria after 90 minutes and declined thereafter; the psiB gene may be repressed when F plasmid replicates vegetatively. PsiB protein may be induced zygotically so as to protect F single-stranded DNA transferred upon conjugation. PsiB protein, when overproduced, may interfere with RecA protein at chromosomal single-stranded DNA sites generated by discontinuous DNA replication, thus causing an SOS inhibitory phenotype.


Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Medically Attended Lower Respiratory Tract Infection and Pneumonia Among Older Adults.
Among older adults, 13-valent pneumococcal conjugate vaccine (PCV13) has been found efficacious against nonbacteremic pneumonia associated with vaccine-serotype pneumococci. However, the burden of lower respiratory tract infection (LRTI) and pneumonia preventable by direct immunization of older adults continues to be debated. We analyzed data from an open cohort of adults aged ≥65 years enrolled in Kaiser Permanente Southern California health plans from 2016 to 2019 who received PCV13 concordant with US Advisory Committee on Immunization Practices guidelines. We estimated PCV13 vaccine effectiveness (VE) via the adjusted hazard ratio for first LRTI and pneumonia episodes during each respiratory season, comparing PCV13-exposed and PCV13-unexposed time at risk for each participant using a self-matched inference framework. Analyses used Cox proportional hazards models, stratified by individual. Among 42 700 adults who met inclusion criteria, VE was 9.5% (95% confidence interval [CI], 2.2% to 16.3%) against all-cause medically attended LRTI and 8.8% (95% CI, -.2% to 17.0%) against all-cause medically attended pneumonia. In contrast, we did not identify evidence of protection against LRTI and pneumonia following receipt of the 23-valent pneumococcal polysaccharide vaccine. PCV13 prevented 0.7 (95% CI, .2 to 1.4) and 0.5 (95% CI, .0 to 1.0) cases of LRTI and pneumonia, respectively, per 100 vaccinated persons annually; over 5 years, 1 case of LRTI and 1 case of pneumonia were prevented for every 27 and 42 individuals vaccinated, respectively. PCV13 vaccination among older adults substantially reduced incidence of medically attended respiratory illness. Direct immunization of older adults is an effective strategy to combat residual disease burden associated with PCV13-type pneumococci.


Measurement of visual evoked potential in the asphyctic fetus and during neonatal survival.
Visual evoked potentials were measured in eight exteriorized near-term fetal lambs prior to and during 8 minutes of asphyxia and during 1 hour of newborn survival. Four of the lambs were then extubated, and measurements were continued while the lambs were observed for behavior and gross motor function. Early in the asphyctic period, marked changes in the visual evoked potential occurred in association with a fall in Po2, whereas during the postexposure period the visual evoked potential appeared to recover independently of cardiovascular or arterial blood gas values. Moreover, early wave components of the visual evoked potentials were more resistant to asphyxia than were later components and responded more quickly to resuscitative efforts. During the survival period the visual evoked potential did not correlate with gross motor function when animals were exposed to moderate acidosis. After severe acidosis abnormal visual evoked potentials were seen during periods of clinical deterioration.


Benign mixed epithelial stromal tumor of the renal pelvis with exophytic growth: case report.
Mixed epithelial and stromal tumor (MEST) is a distinctive benign composite neoplasm of the kidney predominantly seen in females mostly in the perimenopausal period. Although these tumors are known to arise from renal pelvis, our case was distinct in that it had no intrapelvic component growing in exophytic fashion. A 35 year old female patient presented to us with vague abdominal pain. She had undergone excision of bilateral ovarian cystic masses for cystic teratoma twelve years earlier. A computed tomography scan of abdomen and pelvis showed a 9 x 7 cm uniformly solid mass with poor contrast enhancement situated in the inferomedial aspect of the left kidney. On exploration, the mass was arising from the inferior and anterior aspect of left renal pelvis, and was attached to it with a narrow pedicle. There was no adherence or attachment to the renal parenchyma. The mass was excised preserving the kidney. Microscopically, the tumor was composed of large collagenized areas containing bundles of spindle cells and several 'microcysts' lined by cuboidal epithelium suggestive of a benign mixed epithelial stromal tumor. Mixed epithelial tumors usually present in perimenopausal women as a partially cystic mass. Tumors are composed of irregular mixtures of cystic and solid areas, glands with variable complexity and distribution and the stromal component is characterized by a spindle cell proliferation. Commonly, it arises from the renal parenchyma and pelvis and nephrectomy is advocated to manage these tumors. MEST is a distinctive benign tumor of the kidney that should be distinguished from other renal neoplasms. MEST arising from the renal pelvis and growing exophytically is a rare entity. The overall prognosis is favorable.


Can Digitization of Health Care Help Low-Resourced Countries Provide Better Community-Based Rehabilitation Services?
In the wake of globalization, proliferation of digital technologies (DTs) is rapidly changing many activities across sectors, including influencing health to "go digital." Harnessing opportunities of DTs can be a pathway for delivery of health services, such as community-based rehabilitation (CBR) to the vulnerable groups of populations, particularly those in countries with low resources where health systems are weak and experiencing a deficit of trained health workers necessary to effectively deliver a full spectrum of health services. This perspective explored how some DTs can be leveraged in delivery of CBR services in rural and remote areas of countries with low resources. This is described based on information access and exchange, social satisfaction, shortages of rehabilitation workforce, professional development, and capacity building. However, since seizing advantages of DTs can inevitably be associated with spillovers and limitations, including needs prioritization, skills and language limitations, internet addiction and censorship issues, professionalism and ethical dilemmas, and sustainability, if proper measures are not taken, a caution is made. Moreover, as DTs are revolutionizing various activities across sectors, including health, this is not meant as a substitute for traditional health care activities, including those delivered through CBR, but rather to augment their delivery in settings with low resources and elsewhere.