Determining What Represents Value in the Treatment of Refractory or Unexplained Chronic Cough from the Perspective of Key Stakeholders in Spain Using Multi-Criteria Decision Analysis.
Chronic cough is defined as cough lasting for more than 8 weeks. It can be described as refractory when persisting despite thorough clinical assessment and treatment of any cough-related underlying condition, or unexplained when no underlying cough-related condition can be identified. Refractory or unexplained chronic cough (RCC|UCC) greatly affects patient health-related quality of life (HRQoL). Although around 10% of the population suffer from chronic cough (with 40-60% of these patients suffering from RCC|UCC), there is limited information available in the literature about the condition and the assessment of treatment success. This study aimed to determine what represents value in the treatment of RCC|UCC from the perspective of key stakeholders in Spain using Multi-Criteria Decision Analysis (MCDA) methodology. A literature review was conducted to adapt the MCDA framework to the specific context of RCC|UCC. A total of 24 participants were involved, representing three key stakeholder groups (7 patients, 9 physicians and 8 hospital pharmacists). The study was structured in two phases. In Phase 1, participants validated the adapted MCDA framework and assigned relative weights (100-point allocation) to the framework's value criteria/sub-criteria during three individual stakeholder meetings, one per each stakeholder group. In Phase 2, participants were brought together in a multi-stakeholder meeting to review findings of each stakeholder group, after which stakeholders repeated the weighting exercise as a collective group. All meetings included reflective discussion by participants of each value criteria/sub-criteria included within the adapted MCDA framework, where stakeholders shared their perspectives and opinions on what represents value in RCC|UCC. Refractory or unexplained chronic cough is regarded as a chronic medical condition, with variable severity across patients and the potential to heavily impact their HRQoL (including physical, psychological and social/work productivity domains). Current treatments used by healthcare professionals, which have not been specifically developed and are not approved for RCC|UCC, show limited clinical effectiveness and associated safety and tolerability issues, which result in frequent treatment discontinuations. The reduction of the average cough frequency over a 24-h period is regarded as the primary goal of treatment by stakeholders, with the aim of improving HRQoL. Improvement of other cough symptoms, such as intensity, is also considered important. Minor adverse events and a slower onset of treatment effect would be acceptable to stakeholders if accompanied by strong efficacy and improvement in HRQoL. Given the inability to measure cough frequency in clinical practice, Patient-Reported Outcomes (PROs) could be considered a proxy of treatment effectiveness. A multidisciplinary approach to the condition is regarded as key for treatment success. Refractory or unexplained chronic cough is a medical condition that seriously impacts patients' HRQoL. The primary goal of treatment is to improve patients' HRQoL by reducing the frequency and intensity of cough.


Physicochemical evaluation of acid-base disorders after liver transplantation and the contribution from administered fluids.
To analyze the mechanism of acid-base disorders in liver transplant recipients and to examine the relationship between these disorders and the fluids administered during surgery. This prospective study in a university-affiliated hospital intensive care unit (ICU) included 52 patients admitted to the ICU from December 2009 to January 2011. We examined the contributions of inorganic ion differences, lactate, unmeasured anions, phosphate, and albumin to metabolic acidosis. In addition to laboratory variables, we collected demographic and clinical data. Metabolic acidosis (standard base excess ≤ -2.0 mmol/L) was identified in 37 (71.2%) patients during the immediate postoperative period. The inorganic ion difference was the main determinant of acidosis, accounting for -6.17 mEq/L of acidifying effect. The acidemia was attenuated mainly by the alkalinizing effect of albumin reduction, which contributed +6.03 mEq/L. There was an inverse proportional relationship between the quantity of saline solution used during surgery and the inorganic ion difference during the immediate postoperative period. Hyperchloremia is the primary contributor to metabolic acidosis in liver transplant recipients. Possibly the use of chloride-rich solutions increases the incidence of this disorder.


Rapid flattening of massive hemorrhagic retinal pigment epithelial detachment secondary to polypoidal choroidal vasculopathy after surgery.
To report 2 polypoidal choroidal vasculopathy (PCV) patients whose massive hemorrhagic pigment epithelial detachments (PEDs) were flattened within a short period after surgery. Two PCV patients who presented with submacular hemorrhage and massive hemorrhagic PEDs with sizes of more than 50 disc areas underwent pars plana vitrectomy combined with subretinal injection of tissue plasminogen activator (tPA), intravitreous injection of anti-vascular endothelial growth factor medicine, and perfluoropropane tamponade. The massive hemorrhagic PEDs were flattened within a short period after both surgeries, and both patients experienced improved visual acuity. These findings suggest that subretinal injection of tPA together with perfluoropropane tamponade promotes the rapid clearance of hemorrhage under RPE.


Temporal and spatial pattern of dust storms, their polycyclic aromatic hydrocarbons, and human health risk assessment in the dustiest region of the world.
This study evaluated the concentration and health risks of polycyclic aromatic hydrocarbons (PAHs) in Abadan City under 4 different climatic conditions: normal days, dusty days, dust with northwesterly winds, and dust with southeasterly winds. It also determined the sources of aromatics and discussed the relationship between meteorological parameters and PAH concentrations. The spatiotemporal distribution of dust in the area was determined using the HYSPLIT (hybrid single-particle Lagrangian integrated trajectory) back trajectory model, moderate resolution imaging spectroradiometer (MODIS) images. For this purpose, sampling was performed for 70 days using an Omni device. The concentrations of 16 PAHs (USEPA) ranged from 46.22 to 90.96 ng/m3. The highest concentration of high molecular weight (HMW) PAHs was 4-6 rings, of which 4 rings were predominant in all samples. PAH sources were identified using diagnostic ratios and principal component analysis (PCA), and it was shown that PAHs mainly originate from a mixture of sources, including vehicular emissions, petrol emissions, and traffic. Wind speed was negatively correlated with dust, except on dusty days. This result indicates a decrease in PAH concentrations when wind speed increases. On the other hand, the dust correlation with PAH was positive on normal days, but a negative correlation was observed on dusty days. This result was due to the lower concentration of PAHs from natural resources (such as dust source areas) vs. human resources (such as traffic and industry). PAH health risk assessment in Abadan City showed that the risk of carcinogenesis was higher on normal days and through skin contact. The probability of incremental lifetime cancer risk (ILCR) in all sampling conditions was potential in terms of carcinogenic risk (10-4-10-6). As a critical risk factor, relevant authorities should prevent, control, and reduce it.


Peroxynitrite formation mediates LPC-induced augmentation of cardiac late sodium currents.
Lysophosphatidylcholine (LPC) accumulates in the ischaemic myocardium and is arrhythmogenic. We have examined the mechanisms underlying the effects of LPC on the late cardiac Na(+) current (I(L)Na). Na(+) currents were recorded in HEK293 cells expressing Na(V)1.5 and isolated rat ventricular myocytes. LPC enhanced recombinant I(L)Na, while it reduced peak Na(+) current. Computer modeling of human ventricular myocyte action potentials predicted a marked duration prolonging effect and arrhythmogenic potential due to these effects of LPC on peak and late currents. Enhancement of recombinant I(L)Na was suppressed by the antioxidant ascorbic acid and by the NADPH oxidase inhibitor DPI. Inhibitors of the mitochondrial electron transport chain (rotenone, TTFA and myxothiazol) were without effect on LPC responses. The superoxide donor pyrogallol was without effect on I(L)Na. Enhancement of I(L)Na was abrogated by the NOS inhibitors l-NAME and 7-nitroindazole, while LPC induced an l-NAME-sensitive production of NO, measured as enhanced DAF-FM fluorescence, in both HEK293 cells and ventricular myocytes. Despite this, the NO donors SNAP and SNP caused no change in I(L)Na. However, SNAP enhanced TTX-sensitive recombinant and native I(L)Na in the presence of pyrogallol, suggesting peroxynitrite formation as a mediator of the response to LPC. In support of this, the peroxynitrite scavenger FeTPPS prevented the response of I(L)Na to LPC. Peroxynitrite formation provides a novel mechanism by which LPC regulates the late cardiac Na(+) current.


Sutureless clear corneal DSAEK with a modified approach for preventing pupillary block and graft dislocation: case series with retrospective comparative analysis.
The purpose of this study was to describe a modified technique of sutureless DSAEK with continuous pressurized internal air tamponade. This was a prospective interventional case series, single-center, institutional study. Twenty-seven patients with corneal decompensation without scarring were included. Aphakic patients and patients with cataractous lens requiring IOL implantation surgery were excluded. Following preparation of the donor tissue, a corneal tunnel was made nasally with two side ports. All incisions were kept long enough to be overlapped by the peripheral part of the donor tissue. Descemet membrane scoring was done using a reverse Sinskey hook, following which it was removed with the same instrument or by forceps. The donor lenticule was then inserted using Busin's glide. Continuous pressurized internal air tamponade was achieved by means of a 30-gauge needle, inserted through the posterior limbus, for 12-14 min. At the end of the surgery, air was partially replaced with BSS, leaving a moderate-sized mobile air bubble in the anterior chamber. At the 6 month's follow-up, CDVA improved from counting fingers at half meter-6/24 preoperatively to 6/9-6/18 postoperatively, and the mean endothelial cell count decreased: to 1,800 from 2,200 cell/mm(2) preoperatively (18.19 % endothelial cell loss). Donor lenticule thickness as documented on AS-OCT was 70-110 µ on Day 1 and 50-80 µ at 6 months postoperative. None of the cases had flat AC or peripheral anterior synechiae formation. None of the patients required a second intervention. There were no cases of primary graft failure, pupillary block glaucomax or donor lenticule dislocation postoperatively. Our modified technique is simple and effective with reduction in postoperative complications associated with DSAEK, thereby maximizing anatomic and functional outcomes associated.


The amount of DNA in cells of the granular layer of the cerebellum and their susceptibility to hypoxia.
Purkinje cells of the cerebellum are particularly susceptible to hypoxia. In these cells tetraploidy has been demonstrated. Therefore, a link between the susceptibility of cells of the cerebellum to hypoxia and the amount of DNA seems probable.


Integrated microbial electrolysis with high-alkali pretreated sludge digestion: Insight into the effect of voltage on methanogenesis and substrate metabolism.
Integrated microbial electrolysis with anaerobic digestion is proved to be an effective way to improve methanogenesis efficiency of waste activated sludge (WAS). WAS requires pretreatment for efficient improvement of acidification or methanogenesis efficiency, but excessive acidification may inhibit the methanogenesis. In order to balance these two stages, a method for efficient WAS hydrolysis and methanogenesis has been proposed in this study by high-alkaline pretreatment integrated with microbial electrolysis system. The effects of pretreatment methods and voltage on the normal temperature digestion of WAS have also been further investigated with emphasis on the effects of voltage and substrate metabolism. The results show that compared to low-alkaline pretreatment (pH = 10), high-alkaline pretreatment (pH > 14) can double the SCOD release and promote the VFAs accumulation to 5657 ± 392 mg COD/L, but inhibit the methanogenesis process. Microbial electrolysis can alleviate this inhibition effectively through the rapid consumption of VFAs and speeding up of the methanogenesis process. The optimal methane yield of the integrated system is 120.4 ± 8.4 mL/g VSS at the voltage of 0.5 V. Enzyme activities, high-throughput and gene function prediction analysis reveal that the cathode and anode maintain the activity of methanogens under high substrate concentrations. Voltage positively responded to improved methane yield from 0.3 to 0.8 V, but higher than 1.1 V is found to be unfavorable for cathodic methanogenesis and results in additional power loss. These findings provide a perspective idea for rapid and maximum biogas recovery from WAS.


Synthesis and antikinetoplastid activity of a series of N,N'-substituted diamines.
A series of 25 N,N'-substituted diamines were prepared by controlled reductive amination of free aliphatic diamines with different substituted benzaldehydes. The library was screened in vitro for antiparasitic activity on the causative agents of human African trypanosomiasis, Chagas' disease and visceral leishmaniasis. The most potent compounds were derived from a subset of diamines that contained a 4-OBn substitution, having a 50% parasite growth inhibition in the submicromolar (against Trypanosoma cruzi) or nanomolar (against Trypanosoma brucei and Leishmania donovani) range. We conclude that members of this series of N,N'-substituted diamines provide new lead structures that have potential to treat trypanosomal and leishmanial infections.


Frailty in People with Chronic Limb Threatening Ischemia and Diabetes-Related Foot Ulcers: A Systematic Review.
Frailty represents a state of multisystem impairment that may adversely impact people presenting with chronic limb-threatening ischemia (CLTI) and diabetes-related foot ulcers (DFUs). The aim of this systematic review was to explore the association between frailty and outcomes from CLTI and DFUs. We performed a systematic literature search of electronic databases to find studies using a validated measure of frailty in individuals with CLTI and/or DFUs. The primary outcomes were the impact of frailty on the severity of initial clinical presentation and unfavorable follow-up outcomes including readmissions, major limb amputation, cardiovascular events, revascularization, and wound healing. Ten cohort studies were included. Two studies had a low risk of bias, 1 was unable to be assessed, 5 had moderate risk of bias, and 2 high risk of bias. The prevalence of frailty in people presenting with CLTI ranged from 27% to 88% and was 71% in people with DFUs. The presence of frailty in both people with CLTI and DFUs was associated with substantially increased severity at presentation (severity of ischemia and tissue loss) and poorer outcomes at follow-up (risk of readmission, limb amputation, and all-cause mortality). The presence of frailty in both people with CLTI and DFUs is likely associated with substantially higher complexity at presentation followed by a greater risk for readmission, amputation, and death during follow-up. Heterogeneity in the tools used to screen for frailty, poor definition of frailty, and unclear evaluation of exposure and outcomes limit further interpretation of findings.


BOD biosensors for pulp and paper industry wastewater analysis.
Two semi-specific microbial biosensors were constructed for the analysis of biochemical oxygen demand (BOD) in high-cellulose-content pulp and paper industry wastewaters. The biosensors were based on living cells of Bacillus subtilis and Paenibacillus sp. immobilized in an agarose gel matrix. Semi-specific microorganisms were isolated from various samples (decaying sawdust and rabbit manure) and were chosen based on their ability to assimilate cellulose. The biosensors were calibrated with the Organization for Economic Cooperation and Development synthetic wastewater, and measurements with different wastewaters were conducted. The response time of biosensors using the steady-state method was 20-25 min, and the service life of immobilized microorganisms was 96 days. Detection limit was 5 mg/l of BOD(7) while linear ranges extended up to 55 and 50 mg/l of the BOD(7) for B. subtilis- and Paenibacillus sp.-based biosensors, respectively. Repeatability and reproducibility of both biosensors were within the limits set by APHA-less than 15.4%. In comparison, both biosensors overestimated the BOD(7) values in paper mill wastewaters and underestimated the BOD(7) in aspen pulp mill wastewater. The semi-specific biosensors are suitable for the estimation of organic pollution derived from cellulose, while the detection of pollution derived from tannins and lignins was minor. Better results in terms of accuracy and repeatability were gained with Paenibacillus sp. biosensor.


Proposal for best practice in the use of video-EEG when psychogenic non-epileptic seizures are a possible diagnosis.
The gold-standard for the diagnosis of psychogenic non-epileptic seizures (PNES) is capturing an attack with typical semiology and lack of epileptic ictal discharges on video-EEG. Despite the importance of this diagnostic test, lack of standardisation has resulted in a wide variety of protocols and reporting practices. The goal of this review is to provide an overview of research findings on the diagnostic video-EEG procedure, in both the adult and paediatric literature. We discuss how uncertainties about the ethical use of suggestion can be resolved, and consider what constitutes best clinical practice. We stress the importance of ictal observation and assessment and consider how diagnostically useful information is best obtained. We also discuss the optimal format of video-EEG reports; and of highlighting features with high sensitivity and specificity to reduce the risk of miscommunication. We suggest that over-interpretation of the interictal EEG, and the failure to recognise differences between typical epileptic and nonepileptic seizure manifestations are the greatest pitfalls in neurophysiological assessment of patients with PNES. Meanwhile, under-recognition of semiological pointers towards frontal lobe seizures and of the absence of epileptiform ictal EEG patterns during some epileptic seizure types (especially some seizures not associated with loss of awareness), may lead to erroneous PNES diagnoses. We propose that a standardised approach to the video-EEG examination and the subsequent written report will facilitate a clear communication of its import, improving diagnostic certainty and thereby promoting appropriate patient management.


Multigenerational exposure to ethinyl estradiol affects bone geometry, but not bone mineral density in rats.
Estrogenic compounds are known to prevent bone loss in ovariectomized adult rats; however, their effects on bone in developing and reproductively-intact rats are less well-understood. In a large multigenerational experiment 0, 2, 10, or 50 ppb ethinyl estradiol (EE) in the diet was fed to intact male and female rats from conception until either weaning, postnatal day 140, or continuously for 2 years. Vertebrae (lumbar and caudal) and femurs were collected from subsets of these animals at necropsy at 48 days, 70 days, 140 days, or 2 years of age and subjected to dual-energy X-ray absorptiometry (DXA) scanning to measure bone mineral density (BMD), bone mineral content (BMC), and bone area. In addition, the length, cross-sectional area, marrow area, and cortical bone area of the femurs were measured directly in all animals at PND 140 and 2 years. Continuous dietary intake of 50 ppb EE decreased body weight by 8-27%. BMD adjusted for body weight was not affected by EE, with the exception of an increase in the caudal vertebrae in males treated with 50 ppb EE. In female rats, continuous treatment with 50 ppb EE decreased length and cross-sectional area of the femur. The length of the femur was decreased in the first two generations following institution of a phytoestrogen-free diet at the initiation of the study in all animals, including controls, but returned to the original length by the third or fourth generation. The cross-sectional area of the femur also varied by generation. In conclusion, a high dose of EE throughout the lifespan resulted in decreased bone size in females, which could reduce the force required to break the bone. Furthermore, dietary changes may have epigenetic effects which persist for multiple generations.


Clinical case report: Sclerosing hemangioma of the liver, a rare but great mimicker.
Atypical hemangioma (including sclerosing and/or hyalinizing hemangioma) of the liver is a rare variant of hepatic hemangioma, which is the most common benign hepatic tumor. Atypical hemangioma can be indistinguishable from malignancy, primary, or metastatic, based on imaging characteristics. We describe a case of a 70-year-old man with weight loss, occasional bloody stool, change in caliber of stool, and laboratory abnormalities who was found to have multiple hepatic lesions concerning for metastases. We demonstrate that knowledge of the appearance of atypical hemangioma and its inclusion in the differential diagnosis of hepatic lesions can alter patient management and be important to consider before invasive therapies are planned.


Heart rate as a possible therapeutic guide for the prevention of cardiovascular disease.
Epidemiologic evidence indicates that an elevated heart rate (HR) is an independent predictor of all-cause and cardiovascular (CV) mortality. Ivabradine, a pure HR-lowering agent, reduces CV events in patients with coronary artery disease (CAD) and chronic heart failure, and indicate that an HR greater than 70 b.p.m. is hazardous. These findings demonstrate not only that an elevated HR is an epiphenomenon of CV risk status but also that an elevated HR itself should be a therapeutic target. In addition, recent epidemiologic evidence demonstrates that the in-treatment HR or HR change predicts subsequent all-cause and CV mortality, independent of the HR-lowering strategy. Characteristics of the in-treatment HR or HR change are also important as possible therapeutic guides for risk management. However, there have been concerns regarding deleterious effects on CV event prevention owing to β-blocker-derived pharmacologic HR reduction. The potential role of HR and its modulation should be considered in future guidance documents.


[Incidence of pathologic ammonia concentrations in the plasma in children with seizure disorders treated with Convulsofin/Convulex and other anticonvulsants in comparison with children with brain damage and healthy children].
In healthy children plasma ammonia concentrations show values from 12.3 to 57.2 mumol/l (80%-range) (group I). We also measured plasma ammonia in epilepsy patients with valproate therapy (group II) and epilepsy patients treated with other anticonvulsiva (group III). In a fourth group there were children with various cerebral lesions without episodes and without anticonvulsiva therapy. There were significant differences between group I and group II and group II and group IV respectively. But no significant differences were found between the patients who were treated with valproate and the patients with cerebral lesions. The data does not allow the plasma ammonia concentration to be taken as a control parameter in children treated with valproate. Ammonia estimation at the beginning of therapy, however, may be used as risk indicator.


Risk factors influencing the short-term results of gastroduodenal perforation.
The purpose of this study was to evaluate the risk factors influencing the short-term results of gastroduodenal perforation to determine the optimal treatment for reducing mortality. A total of 136 patients were retrospectively reviewed and the prognostic factors were examined. Seven patients died within 30 days, with an overall mortality rate of 5.1%. Mortality was significantly worse in those aged 50 years or more, when the leukocyte count was less than 9,500/mm3, when treatment was delayed more than 12h after perforation, in cases of preoperative shock and renal failure, and when associated with liver cirrhosis or an immunocompromised state. Tolerance to the time delay was inversely proportional to age, while the deaths in patients aged 65 years or younger were related to serious concurrent diseases. Shock and renal failure occurred most often in elderly patients as a result of delayed surgery, and the leukocyte count was an age-dependent prognostic indicator. Thus, age, the time interval between perforation and treatment, serious concurrent disease, shock, and renal failure were presumed to be the most important prognostic factors. Although definitive operations were performed on low-risk patients with an acceptably low mortality, it remains to be determined whether simpler procedures should be adopted for high-risk patients.


Enhanced cold field emission of large-area arrays of vertically aligned ZnO-nanotapers via sharpening: experiment and theory.
Large-area arrays of vertically aligned ZnO-nanotapers with tailored taper angle and height are electrodeposited on planar Zn-plate via continuously tuning the Zn(NH3)4(NO3)2 concentration in the electrolyte. Experimental measurements reveal that the field-emission performance of the ZnO-nanotaper arrays is enhanced with the sharpness and height of the ZnO-nanotapers. Theoretically, the ZnO-nanotaper is simplified to a "charge disc" model, based on which the characteristic macroscopic field enhancement factor (γC) is quantified. The theoretically calculated γC values are in good agreement with the experimental ones measured from arrays of ZnO-nanotapers with a series of geometrical parameters. The ZnO-nanotaper arrays have promising potentials in field-emission. The electrochemical synthetic strategy we developed may be extended to nanotaper arrays of other materials that are amenable to electrodeposition, and the "charge disc" model can be used for quasi-one-dimensional field emitters of other materials with nano-sized diameters.


Laparoscopic treatment of biliary peritonitis following nonoperative management of blunt liver trauma.
Nonoperative management (NOM) of hemodynamically stable patients with blunt hepatic injuries is considered the current standard of care. However, it is associated with several in-hospital complications. In selected cases laparoscopy could be proposed as diagnostic and therapeutic means. A 28 years-old male was admitted in the Emergency Unit following a motor vehicle crash. CT-scan showed an isolated stade II hepatic injury at the level of the segment IV. Firstly a NOM was decided. Laparoscopic exploration was then performed at day 4 due to a biliary peritonitis. Intraoperative trans-cystic duct cholangiography showed a biliary leaks of left hepatic biliary tract, involving sectioral pedicle to segment III. Cholecystectomy, trans-cystic biliary drainage, application of surgical tissue sealing patch and abdominal drainage were performed. Postoperative outcome was uneventful, with fast patient recovery. Laparoscopy has gained a role as diagnostic and therapeutic means in treatment of complications following NOM of blunt liver trauma. This approach seems feasible and safety, with satisfactory postoperative outcome.


Erratum: Comparative Assessment of the Apoptotic Potential of Silver Nanoparticles Synthesized by Bacillus Tequilensis and Calocybe Indica in MDA-MB-231 Human Breast Cancer Cells: Targeting p53 for Anticancer Therapy [Corrigendum].
[This corrects the article DOI: 10.2147/IJN.S83953.].


Keratin polypeptide profile in psoriatic epidermis normalized by treatment with etretinate (aromatic retinoid Ro 10-9359).
The variations in the expression of epidermal keratins occurring during retinoid therapy were studied in patients with psoriasis before and during oral administration of etretinate (aromatic retinoid Ro 10-9359) and compared with normal epidermis. Sodium dodecyl sulfate polyacrylamide gel electrophoresis densitometric readings were performed on keratins extracted from epidermal cells obtained through trypsinization of skin specimens. Epidermal cells were also tested by immunofluorescence (IF) for the presence of BMZ antigens as markers of basal cells and for the presence of TK and KP (67 K, 63 K, and 55 K) with sera with antibodies against BMZ antigens and specific antisera for TK and KP. In psoriasis-involved epidermis, SDS-PAGE anaLysis showed lower amounts of 67 K and increased amounts of 63 K and 55 K, as compared with normal epidermis. Low proportions of cells expressing by IF the 67 K and the 63 K were also noted, with a defective expression of these two KP by suprabasal keratinocytes in psoriasis-involved epidermis. During etretinate administration, a return toward the normal electrophoretic pattern and a correction of the defective cellular expression of these two KP were obtained parallel with clinical improvement. These findings indicate the presence in involved psoriatic epidermis of a population of suprabasal keratinocytes that do not express the high-molecular-weight KP and show a normalization of the relative proportions of the KP with etretinate.


The influence of drugs on nasal ciliary movement.
Drugs in nasal preparations, for local use as well as for systemic use, should not interfere with the self-cleaning capacity of the nose, effectuated by the ciliary epithelium. Many drugs and additives, however, have a negative effect on nasal ciliary function. Examples of ciliotoxic agents are lipophilic and mercuric preservatives, local anesthetics, antihistamines, propranolol, and absorption enhancers such as the bile salts. Cholinergic drugs and beta-adrenergic drugs exert a ciliostimulatory effect. It is the purpose of this review to summarize the present knowledge of ciliotoxicity of drugs and additives and to give recommendations for the use of ciliofriendly drugs in nasal preparations.


Inflammatory monocyte gene signature predicts beneficial within group effect of simvastatin in patients with schizophrenia spectrum disorders in a secondary analysis of a randomized controlled trial.
Immune dysregulation has been reported in schizophrenia spectrum disorders (SSD). In the past decade, several trials using anti-inflammatory agents for treatment of SSD have been completed, with so far limited success. One such anti-inflammatory agent used is simvastatin. A recent, large-scale, randomized controlled trial with simvastatin augmentation failed to show improvement in the predefined primary outcome. However, baseline inflammatory profiles were not taken into account. Here we employed a data-driven clustering approach to investigate whether patients with an inflammatory monocyte gene signature respond better to add-on simvastatin treatment than those without such a signature, over a treatment period of 2 years. In 61 patients (60 randomized, 1:1 placebo:simvastatin) and healthy controls, a previously validated monocyte gene expression signature was assessed using quantitative polymerase chain reaction. Resulting delta cycle threshold values were used to identify patient clusters. Two major patient clusters with either up- or downregulated pro-inflammatory factors were detected. Linear mixed models showed a significant three-way interaction between the inflammatory cluster, treatment, and time for psychotic symptoms. Only patients treated with simvastatin who were in the inflammatory group, showed a consistent improvement: symptom severity gradually decreased after 3 months and reached significance after 12 and 24 months compared to baseline (p.adj<0.05). The effects were small, and overall between-group effects were not significant. Here, we show that patient stratification based on inflammatory gene expression might be useful to select appropriate treatment augmentation for patients with SSD, highlighting the need for precision medicine approaches. Our findings corroborate the results of the primary analyses, showing that in the overall group, simvastatin was not effective; however, at the individual level the treatment might make a difference.


Concerns of Primary Care Clinicians Practicing in an Integrated Health System: a Qualitative Study.
Clinician well-being is a major priority for healthcare organizations. However, the impact of workplace environment on clinicians' well-being is poorly understood. Integrated health systems are a particularly relevant type of practice environment to focus on, given the increasing rates of practice consolidation and integration. To improve understanding of the concerns of primary care clinicians (PCCs) practicing in an integrated health system. We analyzed free-text comment box responses offered on a national survey about care coordination by 555 PCCs in the Veterans Health Administration, one of the largest integrated health systems in the USA. A total of 555 PCCs who left free-text comments on a national survey of care coordination in the VHA (30% out of 1862 eligible respondents). Demographics and coordination scale scores were similar between respondents who left comments vs. those who did not. The data were coded and analyzed in line with the grounded theory approach. Key themes were identified by team consensus and illustrative quotations were chosen to illustrate each theme. VHA PCCs described some pressures shared across practice environments, such as prohibitive administrative burden, but also reported several concerns particular to integrated settings, including "dumping" by specialists and moral distress related to a concern for patients. Frustrations due to several aspects of responsibility around referrals may be unique to integrated health systems with salaried clinicians and/or where specialists have the ability to reject referrals. PCCs in integrated health systems feel many of the same pressures as their counterparts in non-integrated settings, but they are also confronted with unique stressors related to these systems' organizational features that restrict clinicians' autonomy. An understanding of these concerns can guide efforts to improve the well-being of PCCs in existing integrated health systems, as well as in practices on their way to integration.


Effect of digoxin and amino sugar cardiac glycoside (ASI-222) on plasma antidiuretic hormone activity.
Digoxin acts at central neural (CNS) as well as peripheral sites after intravenous administration. In contrast, the analog, 3-beta-O(4-amino-4,6-dideoxy-beta-D-galactopyranosyl)-digitoxigenin (ASI-222), cannot cross the blood-brain barrier so it acts only at sites outside the CNS. The effects of these two agents on plasma antidiuretic hormone activity (ADH) were investigated in conscious dogs. Despite previous evidence that digoxin produces reflex decreases in sympathetic nerve activity by activating ventricular receptors with vagal afferents, no decreases in ADH were detected when either digoxin (25 and 50 micrograms/kg) or ASI-222 (38.5 micrograms/kg) were administered intravenously even with preexisting high levels of plasma ADH. In contrast, both digoxin (50 micrograms/kg) and ASI-222 (38.5 micrograms/kg) resulted in increased ADH levels, but only in association with emesis and behavioral changes suggestive of nausea. Cerebroventricular (IVT) injections of digoxin were given, starting with a dose of 0.1 microgram, that were intended to produce a comparable cerebrospinal fluid (CSF) concentration to that associated with the 50 micrograms/kg intravenous dose. Only the highest dose of digoxin, 1 micrograms, but not 0.1 and 0.3 micrograms, produced increases in ADH and emesis when given into the lateral cerebral ventricle. This is further evidence that a site accessible to blood but not to CSF was involved. These results suggest that digoxin and ASI-222 may activate pathways in the area postrema and produce increases in ADH as well as emesis.


Individual variability in the nonlinear development of the corpus callosum during infancy and toddlerhood: a longitudinal MRI analysis.
The human brain spends several years bootstrapping itself through intrinsic and extrinsic modulation, thus gradually developing both spatial organization and functions. Based on previous studies on developmental patterns and inter-individual variability of the corpus callosum (CC), we hypothesized that inherent variations of CC shape among infants emerge, depending on the position within the CC, along the developmental timeline. Here we used longitudinal magnetic resonance imaging data from infancy to toddlerhood and investigated the area, thickness, and shape of the midsagittal plane of the CC by applying multilevel modeling. The shape characteristics were extracted using the Procrustes method. We found nonlinearity, region-dependency, and inter-individual variability, as well as intra-individual consistencies, in CC development. Overall, the growth rate is faster in the first year than in the second year, and the trajectory differs between infants; the direction of CC formation in individual infants was determined within six months and maintained to two years. The anterior and posterior subregions increase in area and thickness faster than other subregions. Moreover, we clarified that the growth rate of the middle part of the CC is faster in the second year than in the first year in some individuals. Since the division of regions exhibiting different tendencies coincides with previously reported divisions based on the diameter of axons that make up the region, our results suggest that subregion-dependent individual variability occurs due to the increase in the diameter of the axon caliber, myelination partly due to experience and axon elimination during the early developmental period.


Cognitive Function in Patients With Chronic Kidney Disease: Challenges in Neuropsychological Assessments.
Cognitive dysfunction is a common symptom in patients with chronic kidney disease (CKD). In this review, we highlight the clinical relevance of cognitive impairment in patients with CKD. After a summary of the different pathophysiological components of this frequently overlooked clinical condition, we summarize and evaluate the available neurocognitive tests and reflect on their utility in everyday clinical practice. Finally, we identify future areas of research and allude to the fact that inclusion of cognitive function testing in routine clinical care of patients with CKD could be cost effective by reducing nonadherence to medication and improving quality of life, and even survival.


Optimizing Sanitation Network Upgrading Projects in Slum Areas.
Infrastructure upgrading projects are a key element in enhancing the livelihood of residents in slum areas. These projects face significant constructability challenges common to dense-urban construction coupled with the unique socioeconomic challenges of operating in slums. This research focuses on sanitation network upgrading projects in slum areas and proposes a novel methodology capable of (1) accounting for the unique constructability challenges for these projects, (2) accelerating the provision of sanitation services, and (3) optimizing construction decisions. The key contribution of this research to the body of knowledge is in developing a comprehensive construction planning framework capable of achieving these three objectives. The proposed framework focuses specifically on sewer lines upgrading within the larger sanitation networks upgrading projects. This framework consists of five main models that can guide planners in selecting the appropriate equipment sizes, trench system configuration, and optimal equipment routing, in addition to identifying all possible execution sequences along with the corresponding construction cost and duration of each sequence. Most notably, this framework proposes an approach to assess the serviceability of different construction plans measured by how fast sanitary services can be provided to slum dwellers. A multi-objective, genetic algorithms optimization model is developed to identify the optimal construction plans that accelerate the sanitary service provision to residents while minimizing construction costs. A real-world example is presented to demonstrate the model capabilities in optimizing construction plans.


Evidence for removal at different rates of O-ethyl pyrimidines and ethylphosphotriesters in two human fibroblast cell lines.
The potent carcinogen, ethylnitrosourea, has been shown to ethylate oxygens, in preference to nitrogens, in the DNA of cultured cells. We have now studied the removal of seven ethyl derivatives in replicating cells. The following findings are reported. 1) The absolute amounts of 02-EtT, 04-EtT and 02-EtC are decreased in cellular DNA after correction for cell growth. However the rate of decrease diminishes after approximately 20 hr and after more than two cell doublings 20--40% of each derivative persists. This decrease is presumed to be due to enzymes since these derivatives are stable in isolated DNA. 2) The amount of ethyl phosphotriesters remains almost unchanged during 72 hr of cell culture. 3) The unstable purine derivatives, 7-EtG and 3-EtA, are both removed from cellular DNA with a rate faster than can be accounted for by the lability of the glycosyl bond. 4) Both GM 637 fibroblasts and Xeroderma pigmentosum fibroblasts (12-RO) (XP-12) have similar ability to remove ethyl products, except for O6-ethyl G which persists to a greater extent in XP12 cells. 5) The implications of the in vivo persistence of ethylated bases is discussed in regard to recent demonstrations that O2-EtT, O4-ET, O2-EtC and O6-EtG are all mutagenic.


"I think there has to be a mutual respect for there to be value": Evaluating patient engagement in a national clinical trial on de-implementation of low value care.
The evaluation of patient engagement in research is understudied and under-reported, making it difficult to know what engagement strategies work best and when. We provide the results of an evaluation of patient engagement in a large Canadian research program focused on the de-implementation of low-value care. We aimed to evaluate the experience and impact of patient engagement in the study. An online cross-sectional survey was administered using Microsoft Forms to (1) researchers and study staff and (2) patient partners. The survey was developed following iterative reviews by the project's patient partnership council and evaluation committee. Survey content areas included opinions on patient engagement to date, including challenges to engagement and suggestions for improvement. Patient partners also evaluated the partnership council. Descriptive statistics including counts and percentages described Likert scale survey items, while open comments were analyzed using descriptive content analysis. The survey response rate was 46% (17/37). There were positive attitudes about the value of patient engagement in this project. There was also a high degree of willingness to be involved with patient engagement in future projects, whether as a patient partner or as a researcher including patients on the research team. Most patient partners felt their contributions to the project were valued by researchers and study research staff. Open comments revealed that a co-design approach and full inclusion on the research team were integral to demonstrating the value of patient partner input. Areas for improvement included more frequent and ongoing communication among all team members, as well as earlier training about patient engagement, particularly addressing role expectations and role clarity. Our data revealed that despite some challenges, team members recognized the value of patient engagement in research and agreed project decisions had been impacted by patient partner input. Ongoing communication was highlighted as an area for improvement, as well as earlier training and ongoing support for all team members, but particularly researchers and study staff. In response to evaluation data, the team has reinstated a quarterly newsletter and plans to use specific patient engagement planning templates across study sites for all project activities. These tools should help make expectations clear for all team members and contribute to a positive patient engagement experience. Findings can inform patient engagement planning and evaluation for other health research projects.


Factors that predict low hematocrit levels in the postpartum patient after vaginal delivery.
The purpose of this study was to provide a viable alternative to routine postpartum hematocrit measurement, by a determination of the clinical risk factors that identify patients with anemia and an examination of the resulting cost savings. In this retrospective review, cases (postpartum hematocrit level, <26%; subgroup hematocrit level, <23%) and control subjects were culled from the records of all vaginal deliveries from February 1997 to July 1998. Charts were reviewed for demographic characteristics, medical history, nursing assessments, and postpartum hematocrit measurements. Logistic regression modeling determined the best set of risk factors for the identification of low postpartum hematocrit levels. From 1484 vaginal deliveries, 117 of the women (8%) had postpartum hematocrit levels of <26%. Estimated blood loss of >500 mL, Hispanic ethnicity, dizziness, or third- or fourth-degree laceration were the factors that identified 82.9% of the women with hematocrit levels of <26% and identified 97.4% of the women with hematocrit levels of <23%. Only 39.3% of the women would have required postpartum hematocrit measurement to obtain these detection rates. Four risk factors (estimated blood loss of >500 mL, Hispanic ethnicity, dizziness, and third- or fourth-degree laceration) can safely determine the necessity of a postpartum hematocrit measurement.


Molecular signaling toward mitophagy and its physiological significance.
Mitochondrial autophagy or mitophagy is a cellular metabolic pathway that mediates the selective elimination of dysfunctional or unwanted mitochondria. Considerable advancements have been made to elucidate the molecular mechanism behind mitophagy, particularly Parkin-mediated mitophagy. Several mitophagy receptors have been discovered in different physiological settings, including ATG32 in yeast as well as NIX, BNIP3, and FUNDC1 in mammalian cells. However, the signaling events that regulate these mitophagy receptors and their physiological significance in human diseases are poorly understood. In this paper, we review recent advancements in mitophagy at the cellular and molecular levels.


New record of Trissolcus solocis (Hymenoptera: Scelionidae) parasitising Halyomorpha halys (Hemiptera: Pentatomidae) in the United States of America.
A parasitoid wasp, Trissolcus solocis Johnson, was recorded parasitising eggs of the invasive stink bug Halyomorpha halys (Stål), in the United States. This is the first record of this species parasitising eggs of H. halys. First record of Trissolcus solocis parasitising Halyomorpha halys eggs in the United States and first record of T. solocis in Alabama.


Meta-analysis of laparoscopic anterior resection with natural orifice specimen extraction (NOSE-LAR) versus abdominal incision specimen extraction (AISE-LAR) for sigmoid or rectal tumors.
Natural orifice specimen extraction surgery is a novel technique of minimally invasive surgery. The purpose of this study was to compare the safety of laparoscopic anterior resection with natural orifice specimen extraction (NOSE-LAR) and abdominal incision specimen extraction (AISE-LAR) for sigmoid or rectum tumors. MEDLINE (PubMed), Embase, CENTRAL (Cochrane Central Register of Controlled Trials), Scopus, and ClinicalTrials databases were systematically searched for related articles up to August 2019. The primary outcomes included postoperative complications (overall postoperative complication, incision-related complication, anastomotic fistula, and severe complication) and pathologic results (lymph nodes harvested, proximal resection margin, and distal resection edge). The statistical analysis was performed on STATA 12.0 software. Ten studies comprising 1787 patients were used for meta-analysis. Compared with AISE-LAR, NOSE-LAR had more advantages in terms of overall postoperative complication (odds ratio (OR) = 0.65 (95% CI, 0.46 to 0.90; P = 0.01)), incision-related complication (OR = 0.13 (95% CI, 0.05 to 0.35; P < 0.01)), distal resection edge (weighted mean difference (WMD) = 0.17 cm (95% CI, 0.02 to 0.33 cm; P = 0.02)), recovery of gastrointestinal function (WMD = - 0.38 day (95% CI, - 0.70 to - 0.06 day; P = 0.02 )), pain scores in postoperative day 1 (WMD = - 1.64 (95% CI, - 2.31 to - 0.98; P < 0.01)), additional analgesics usage (OR = 0.21 (95% CI, 0.11 to 0.40; P < 0.01)) and hospital stay (WMD = - 0.71 day (95% CI, - 1.10 to - 0.32 day; P < 0.01)), while the operation time of NOSE-LAR was prolonged (WMD = 7.4 min (95% CI, 0.17 to 14.64 min; P = 0.04)). The anastomotic fistula, severe complication, lymph nodes harvested, proximal resection margin, intraoperative blood loss, and long-term outcomes in NOSE-LAR were comparable with AISE-LAR. The safety of NOSE-LAR was demonstrated, and it could be an alternative to conventional surgery in laparoscopic anterior resection for sigmoid and rectal tumors. However, further randomized and multi-center trials are required.


Traumatic aortic injuries associated with major visceral vascular injuries in major blunt trauma patients.
The objectives of this study were to report the clinical and radiological characteristics and outcomes of a series of acute traumatic aortic injuries (ATAIs) with associated injury to major aortic abdominal visceral branches (MAAVBs). From January 2000 to August 2011, 10 consecutive major blunt trauma patients with associated ATAI and injury to MAAVBs (group A) and 42 major blunt trauma patients presenting only an ATAI without MAAVB injuries (group B) were admitted to our institution. Overall in-hospital mortality was 32.7%. In-hospital mortality in group A was 40% and in group B it was 31% (p = 0.86). Observed in-hospital mortality was slightly lower than the expected in-hospital mortality in both groups. Mean peak creatine phosphokinase was significantly higher in group A than in group B patients (23,008 ± 33,400 vs. 3,970 ± 3,495 IU/L; p < 0.001). Acute renal injury occurred in 50% of group A and in 26.2% of group B patients. Hemodiafiltration was required in 30% of group A and in 9.5% of group B patients. Median follow-up time was 64 months (range = 1-130 months). Group A survival was 60% at 1, 5 and 10 years. Group B survival was 69% at 1 year and 63.3% at 5 and 10 years (p = 0.15). Aortic injuries associated with MAAVB injuries in major trauma patients seem to present in a different clinical scenario. These patients present increased risk of rhabdomyolysis, visceral ischemia, and acute renal failure, as well as higher in-hospital mortality. A multidisciplinary approach combining endovascular and open surgical techniques for a staged treatment of these life-threatening aortic and MAAVB injuries is mandatory in this critical subset of trauma patients.


Staining of proteins for 2D SDS-PAGE using Coomassie Blue--speed versus sensitivity?
Several new fast staining protocols for the visualization of proteins separated by SDS-PAGE utilizing Coomassie Blue staining (CBS) have been described in literature. The sensitivity of a newly designed staining protocol is usually estimated using 1D SDS-PAGE of serially diluted protein samples. However, this approach is not predictive and satisfactory for 2D SDS-PAGE capable of resolving hundreds or thousands of different proteins in a single analysis. In this work, a new fast staining protocol recently introduced by Dong et al. (PLoS One 2011, 6, e22394) was compared to colloidal CBS. The number of detectable spots in 2D SDS-PAGE of identical blood plasma samples in repeated runs was chosen as a sensitivity criterion. Further, the influence of gel boiling on the subsequent protein identification by MS was investigated. In spite of its advantages, the staining protocol according to Dong et al. (PLoS One 2011, 6, e22394) seems to be less sensitive than colloidal Coomassie staining when the number of detected spots is the evaluating criterion. No obvious influence of gel boiling on the protein identification was observed.


Medium-scale ligand-affinity purification of two soluble forms of human interleukin-2 receptor.
Recombinant technology has facilitated the production of two soluble forms of human interleukin-2 receptor (IL-2R) in Chinese hamster ovary cells. We have developed a ligand-affinity method for the medium-scale purification of these two IL-2Rs, based on the biochemical interactions between the matrix-bound ligand (interleukin-2) and its soluble receptor. The affinity-purified IL-2R is further purified by anion-exchange chromatography followed by gel filtration. This method has provided enough highly pure IL-2R for structure and function studies and for use in practical applications such as high-flux drug screening assays and the receptor-affinity purification of human recombinant interleukin-2.


Epidermoid or dermoid cysts of the ovary? Clinicopathological characteristics of 28 cases and a new pathologic classification of an old entity.
The aim of this study was to present the clinical and pathological findings that aid in the differential diagnosis between epidermoid and dermoid ovarian tumors. This was a 15-year retrospective clinico-pathological study. A total of 28 cases of epidermoid ovarian cysts histologically confirmed after pathological examination at the Pathology Laboratory of Aretaieion University Hospital between January 1996 and December 2010, were analyzed and a literature review was performed. Patients with epidermoid cysts presented with a main complaint of either abdominal pain or a palpable abdominal mass. In the 28 cases studied, 18 patients underwent cystectomy and four cases underwent oophorectomy. In six cases of post-menopausal women, abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. No recurrent disease in the pelvis was reported during the available follow-up period which was from 12 to 30 months. Epithelial epidermoid ovarian tumors represent less than one percent of ovarian surface epithelial tumors. The differential diagnosis of epidermoid cysts includes dermoid (mature cystic teratomas) tumors of the ovary. However, it should be mentioned that up to 17% of teratomas may include epidermoid tumors. In comparison to dermoid cysts which present at an earlier age but with a greater size, ovarian epidermoid tumors present as small- to medium-sized cystic lesions occurring at a significantly older age. The treatment of choice is conservative surgical therapy.


"Teaching somebody else makes you a better person:" A phenomenological exploration of the importance of informal peer support for individuals with spinal cord injury.
Peer support is widely recognized as an important aspect of health promotion for individuals with spinal cord injury (SCI). Reports indicate positive effects for the recipients of either informal and formal peer support. The experience can also be meaningful to the person(s) providing support, although the value to providers is not well studied. This study examines the experience of provision of and receipt of informal peer support for individuals with SCI through semi-structured interviews. Data were analysed using a qualitative phenomenological approach. 16 participants with SCI participated in the study. Three main themes were developed, each describing different benefits of peer support from the perspective of both members of the peer support dyad. First, participants found personal satisfaction from using their own experiences to help others adjust to their disability. Participants also noted that they learned how to complete activities of daily living as well as how to be autonomous in travel from others with SCI. Finally, participants spoke of the intrinsic benefit in teaching others with SCI. This study provides a novel understanding of the importance of informal peer support for individuals with SCI. Practitioners should provide opportunities for individuals with SCI to develop informal peer relationships with others who have sustained SCI.


Avatrombopag, an oral thrombopoietin receptor agonist: results of two double-blind, dose-rising, placebo-controlled Phase 1 studies.
Avatrombopag is an oral thrombopoietin receptor agonist that has been recently approved for treating thrombocytopenia in chronic liver disease patients needing invasive procedures. Clinical trials supporting this new treatment were guided by two double-blind, dose-rising, placebo-controlled Phase 1 studies in healthy adults reported here that assessed safety, tolerability and pharmacokinetic profile of avatrombopag, and its effect on platelet counts. Subjects were randomised (2:1) in the single-dose study (N = 63) to avatrombopag (1, 3, 10, 20, 50, 75 and 100 mg) or placebo, and in the multiple-dose study (N = 29) to avatrombopag (3, 10 and 20 mg) or placebo daily for 14 days. There were no serious adverse events (AEs), dose-limiting toxicities, deaths, AEs causing withdrawal, thromboses or liver function abnormalities. In both studies, avatrombopag peak concentration and exposure increased proportionally relative to dose; half-life was 18-21 h and independent of dose, supporting once-daily dosing. Effects on platelet counts depended on dose, concentration and treatment duration. Platelet count increases began 3-5 days post-administration, with maximum changes of >370 × 109 /l over baseline with 20 mg daily after 13-16 days. These data support continued development of avatrombopag for treatment of other thrombocytopenic conditions and provide important guidance for the haematologist in the use of this new thrombopoietin receptor agonist.


Contrasting roles of layered structures in the molecular assembly of liquid crystal matrices on the viscoelastic properties of microparticle/liquid crystal composite gels leading to rigidification and destabilization.
We investigated the effects of the nematic and smectic A (SmA) phase structures of liquid crystalline matrices on the viscoelastic properties of microparticle/liquid-crystal composite gels. The storage (G') and loss (G″) moduli of the gels were largely increased in gels containing SmA matrices with a layered molecular assembly. However, the critical strain at which the gel state transformed into the sol state by the application of mechanical strain showed no significant changes with variation in the liquid crystal phase of the matrix. These results indicate that the introduction of a layered molecular assembly could be effective for rigidification of composite gels, while maintaining their critical strains. However, the composite gels tended to show a metastable state when SmA matrices were used because G' and G″ of the gels were close to each other in the entire frequency region. This behavior was in contrast to the gels with nematic matrices, which showed a larger value in G' than that in G″. The metastable state of gels with SmA matrices was also reflected in the frequency dependence of G' and in the deterioration of the recovery of the gel state after mechanical breakdown.


Gut microbiome-depleting antibiotic regimens are not tolerated by all mouse strains: learn from (our) bitter experience.
Why the gut microbiome is critical for the success of checkpoint inhibitor cancer therapy is a question that remains unanswered, but progress has slowed. We argue that this lack of advancement is due to an unappreciated biological detail. Here, we show that the antibiotic cocktail used in seminal publications-all of which have used the C57BL/6 mouse strain-are bitter and not tolerated by other common mouse strains (ie, BALB/c and DBA/2). We write to alert readers of this important biological limitation that must be considered when planning cancer experiments investigating the gut microbiota, to prevent the unnecessary dehydration of experimental animals, and to save our colleagues valuable experimental time and resources.


Anterior Shoulder Instability in a Young Individual with Concomitant Coracoid Process Fracture Treated with the Latarjet Procedure - A Rare Case Report.
Coracoid fracture occurs with shoulder instability due to direct humeral head impaction. Incidence coracoid fracture with shoulder dislocation is rare amounts to 0.8-2%. We encountered clinical challenge of unique combination of both shoulder instability and coracoid fracture. This technical note will describe the treatment of the same. A 23-year-old male suffering from recurrent shoulder dislocation sustained coracoid fracture. Further evaluation showed glenoid defect of 25%. Magnetic resonance study showed on track lesion with Hill-Sach lesion of 9 mm, labral defect anteriorly with no associated rotator cuff tear. The patient was managed with open Latarjet procedure with fracture coracoid fragment with conjoint tendon as graft. Our purpose of reporting this technical note is to provide an option of dealing both instability and coracoid fracture in single sitting and usage of coracoid fractured fragment as an excellent graft of choice in acute presentation. However, certain limitations such as adequacy of graft in size and shape do exist operating surgeon which must be aware of the same.


Prostaglandin E1 and dibutyryl cyclic AMP enhance platelet resistance to deformation.
The effect of prostaglandin E1 (PGE1) on platelets is mediated through the PGE1 receptor and the consequent maintenance of the platelet's discoid shape. The effects of PGE1 and dibutyryl cAMP (dbcAMP) on the deformability of human platelets were studied. Deformability tests based upon the micropipette aspiration on the platelets were performed by using pipettes with radii (Rp) of 0.26-0.36 microns. The time course of the extension length (Dp, in microns) of the platelets in response to aspiration with a negative pressure (delta P) of 5 cm H2 O (delta P x Rp = 0.15 dynes/cm) was analyzed. PGE1 treatment (0.1 microM) resulted in a decrease of platelet deformability as compared with results obtained for apparently non-activated, control platelets. The deformation index, i.e., Dp/Rp (PGE1-treated)/Dp/Rp (control), was significantly reduced to 0.90 +/- 0.04. DbcAMP treatment also significantly decreased the deformability of platelets and this decrease was dbcAMP dose dependent. In contrast, colchicine- or cytochalasin D-treated platelets increased deformability. PGE1-treated platelets had a higher [cAMP]i than controls. Platelets treated with PGE1 or dbcAMP showed a reduced [Ca2+]i increment induced by thrombin as compared to non-treated controls. These results indicate that PGE1 and dbcAMP treatment of platelets is accompanied by an enhancement of platelet resistance to deformation. The increased [cAMP]i and low [Ca2+]i after PGE1 treatment may limit the rearrangement of cytoskeleton and thus enhance platelet resistance to deformation.


A survey of office practice: Parents, front office staff, nurses and clinicians hold disparate views on adolescent vaccines.
Previous work suggests provider recommendation improves vaccine delivery. Less examined is the role of practice's front office staff and nurses in vaccine communication. Messaging and communication about vaccines should be consistent across all levels of the pediatric practice. We distributed surveys to clinicians, nurses, front office staff, and parents of adolescents 11-17 years in pediatric and family medicine office practices. We inquired about perceived importance of adolescent vaccines and the use of recommendations to families about receiving vaccines. We also asked front office staff about concerns from families about vaccines as well as vaccine refusal for themselves and their child. Nurses perceived that the HPV vaccine was less important than the MenACWY and Tdap vaccines (% very important 84% v. 95% and 94%; P < .01). Parents also perceived HPV vaccine as being less important than MenACWY and Tdap vaccines (59% v 68% and 79%; P < .01. Between groups, parents perceived all vaccines as being less important than front office staff. Nurses and clinicians reported using a strong recommendation less often for HPV vaccine compared to the MenACWY and Tdap (70% v 84% and 84%; P < .01 for nurses, and 77% v. 88% and 86%; P < .05 for clinicians). Front office staff were more likely to report concerns from parents about HPV vaccine than from MenACWY and Tdap after the visit is complete. Parents, front office staff and nurses differ on the importance of vaccines. Interventions to improve vaccine communication and delivery must include all who work in the practice.


Comparison of the effects of various lengths of synthetic human parathyroid hormone-related peptide (hPTHrP) of malignancy on bone resorption and formation in organ culture.
Parathyroid hormone-related peptide (PTHrP) has been shown to be the pathogenic agent in humoral hypercalcemia of malignancy (HHM), but the molecular forms that are secreted have not been fully characterized. PTHrP 1-34 has effects similar to parathyroid hormone (PTH), but C-terminal regions of the peptide, such as the 107-139 fragment found to inhibit resorption in a study by Fenton et al (1991), may have other biological activities not shared with PTH. We have compared the effects of the longer forms of recombinant human PTHrP (hPTHrP 1-84, 1-108, and 1-141) with hPTHrP 1-34 and synthetic bovine PTH (bPTH) 1-34 on bone resorption and formation in cultured neonatal mouse calvariae and fetal rat long bones. hPTHrP 1-84, 1-108, and 1-141 were qualitatively similar to hPTHrP 1-34 and PTH 1-34 in stimulating 45Ca release from both neonatal mouse calvariae and fetal rat long bones and in inhibiting the incorporation of [3H]-proline into collagenase digestible protein (CDP) and stimulating the incorporation of [3H]-thymidine (3H-TdR) in neonatal mouse calvariae. However, hPTHrP 1-108 and 1-141 were less potent at stimulating 45Ca release and inhibiting CDP labeling than hPTHrP 1-34, while hPTHrP 1-84 showed an intermediate potency. Since hPTHrP 1-108 and 1-141 were quite similar in potency, the difference cannot be attributed to an inhibitory effect of the 107-139 fragment. All the peptide lengths tested showed similar potency in stimulating [3H]-TdR incorporation.(ABSTRACT TRUNCATED AT 250 WORDS)


Pharmacokinetics of cocaine in pregnant and nonpregnant rhesus monkeys.
To determine pharmacokinetic parameters for cocaine in rhesus monkey plasma, samples were taken over several hours after i.m. administration of cocaine plus a tritiated cocaine tracer. Cocaine and its metabolites, benzoylecgonine and norcocaine, were isolated via HPLC and quantitated using liquid scintillation spectrometry. Pregnant subjects were dosed with cocaine at 0.3 (n = 3) or 1.0 (n = 3) mg/kg, whereas nonpregnant female subjects were dosed with 1.0 mg/kg (n = 3). For the pregnant subjects, pharmacokinetic studies were conducted on about gestational day 125 and areas under the concentration versus time curve (AUCs, ng/mL x h) were 64 +/- 26 (+/- SEM) and 143 +/- 12; half-lives (t1/2s, h) were 1.9 +/- 0.6 and 1.1 +/- 0.1 after 0.3 and 1.0 mg/kg i.m., respectively. For nonpregnant subjects dosed acutely with 1.0 mg/kg, the AUC was 262 +/- 63 and the t1/2 was 1.4 +/- 0.3. There appear to be few differences in the pharmacokinetic parameters of cocaine and benzoylecgonine between pregnant and nonpregnant monkeys in this study.


Pharmacological treatment of erectile dysfunction after radical prostatectomy.
The potential for potency after radical retropubic prostatectomy has improved considerably since the anatomical description of the neurovascular bundles to the penis and a technique whereby these nerves may be spared from injury. However, impotence remains an unavoidable complication in some patients. It is in such patients that we have chosen to evaluate the technique of intracavernosal injection of a papaverine/phentolamine mixture to obtain erections. After classical radical prostatectomy potency was restored by the injection technique in 12 of 14 patients (85 per cent). Three patients who failed to attain erections initially had successful results with larger doses. Two patients who failed to achieve erections had the lowest penile brachial index values and 1 in whom priapism developed had the highest value, indicating that this may be a useful technique to determine the initial dosage of the injection.


Heavy metal levels in milk and dairy products and health risk assessment: A systematic review of studies in China.
Previous studies have indicated that heavy metal levels in milk vary partly depending on environmental metal concentrations. Given the increasing consumption of milk in China, it is essential to pay attention to milk safety. We performed a systematic review of relevant published studies to evaluate the heavy metal levels in milk and dairy products and the associated health risks, discuss environmental sources of heavy metals, and propose future research directions. A literature search was implemented in the Web of Science Core Collection and PubMed using multiple keywords such as "metal," "milk," "dairy products," and "China". A total of 16 published studies that analyzed metal levels in milk and dairy products in 20 provincial administrative regions were included. Most studies detected toxic heavy metals in milk and dairy products samples, including mercury, lead, cadmium, chromium, and arsenic. The lead concentration in milk from these studies did not exceed the Chinese standard for milk. However, three studies detected relatively high lead levels in both commercial and raw milk, exceeding the European Commission standard. The polluted environment surrounding the farm, feed, and packaging materials are likely sources of metals in milk and dairy products. The hazard index for the 11 analyzed metal elements in milk and dairy products was lower than 1, indicating negligible non-carcinogenic health risks from exposure to these metals. Children are at a higher risk than adults. This review illustrates that research in this field is limited to China. More research should be conducted in the future, such as evaluating the contribution of each environmental source of metal in milk and dairy products.


Characterisation of a gene cluster in Fugu rubripes containing the complement component C4 gene.
In this study, we describe the characterisation of the complement component C4 gene in Fugu rubripes. The Fugu C4 gene, orthologous to the tetrapod C4 gene, encompasses a genomic span of 9702 base pairs and contains 41 exons, encoding the typical C4 three-chain polypeptide. The gene encodes a protein containing 1703 amino acids. The Fugu C4 protein demonstrates the presence of 25 conserved cysteine residues, as well as conservation of the functionally important thioester site. Complete sequencing of one cosmid and sequence scans from a cluster of 18 overlapping BAC clones, centering around the C4 gene, have identified the short-range linkage with five orthologous human genes mapping to the Major Histocompatibility Complex (MHC) including: tenascin X (TNX); cytochrome P450, subfamily XXIA, polypeptide 2 (CYP21A2); allograft inflammatory factor 1 (AIF1) and casein kinase 2, beta polypeptide (CSNK2B), all found in the MHC class III region; and retinoid X receptor, beta (RXRB),which resides in the MHC extended class II region. To date, this syntenic association of the Fugu C4 and other MHC class III region genes has not been observed in other teleost fish. Data from the recent whole-genome shotgun assemblies reveal the Fugu MHC-related cluster of genes to be flanked predominantly by genes mapping to human chromosomes 7 and 19. All of the six identified Fugu MHC-related genes have been characterised at the genomic level.


An Updated Overview of Existing Cancer Databases and Identified Needs.
Our search of existing cancer databases aimed to assess the current landscape and identify key needs. We analyzed 71 databases, focusing on genomics, proteomics, lipidomics, and glycomics. We found a lack of cancer-related lipidomic and glycomic databases, indicating a need for further development in these areas. Proteomic databases dedicated to cancer research were also limited. To assess overall progress, we included human non-cancer databases in proteomics, lipidomics, and glycomics for comparison. This provided insights into advancements in these fields over the past eight years. We also analyzed other types of cancer databases, such as clinical trial databases and web servers. Evaluating user-friendliness, we used the FAIRness principle to assess findability, accessibility, interoperability, and reusability. This ensured databases were easily accessible and usable. Our search summary highlights significant growth in cancer databases while identifying gaps and needs. These insights are valuable for researchers, clinicians, and database developers, guiding efforts to enhance accessibility, integration, and usability. Addressing these needs will support advancements in cancer research and benefit the wider cancer community.


Bacterial lipopolysaccharide regulates the phosphorylation of the 68K protein kinase C substrate in macrophages.
Bacterial lipopolysaccharide (LPS) potentiates protein kinase C (PKC)-dependent responses such as the activation of arachidonic acid metabolism in macrophages (Aderem, A. A., Cohen, D. S., Wright, S. D., and Cohn, Z. A. (1986) J. Exp. Med. 164, 165-179). Concomitantly, LPS promotes the myristoylation of a 68K PKC substrate, shown to be equivalent to the 80/87K PKC substrate found in brain and fibroblasts (Aderem, A. A., Albert, K. A., Keum, M. M., Wang, J. K., Greengard, P., and Cohn, Z. A. (1988) Nature 332, 362-364). We have now examined the effect of LPS on the phosphorylation of this 68K PKC substrate. We report here that LPS modifies the kinetics and extent of phosphorylation of the 68K protein. While treatment with LPS alone induces low level phosphorylation of the 68K protein, it markedly increases the rate of subsequent phorbol 12-myristate 13-acetate (PMA)-dependent phosphorylation of this protein. Phosphorylation in LPS-treated macrophages was maximal 1-2 min after administration of PMA, while maximal phosphorylation in macrophages not exposed to LPS was only achieved 6 min after addition of PMA. In addition to increasing the rate of PMA-dependent phosphorylation of the 68K protein in macrophages, LPS also promoted the phosphorylation of a novel peptide on the 68K protein. Thus while PMA stimulated the phosphorylation of two thermolytic phosphopeptides (phosphopeptides 1 and 2), the low level of phosphorylation observed with LPS alone was found to occur on phosphopeptides 1 and 2 as well as on a novel phosphopeptide (phosphopeptide 3). Furthermore, LPS treatment of macrophages potentiated phosphorylation of all three phosphopeptides when the cells were subsequently stimulated with PMA. While phosphorylation stimulated by LPS and PMA was slightly more than additive for phosphopeptides 1 and 2, it was markedly synergistic (increased 14.5-fold) for phosphopeptide 3. Phosphorylation of all three phosphopeptides occurred exclusively on serine. It is possible that LPS-induced myristoylation of the 68K protein directs it to the membrane where its phosphorylation is enhanced by its close association with PKC.


Correlates of intentional tanning among adolescents in the United States: a systematic review of the literature.
Exposure to ultraviolet radiation and a history of sunburn in childhood contribute to risk of skin cancer in adolescence and in adulthood, but many adolescents continue to seek a tan, either from the sun or from tanning beds (i.e., intentional tanning). To understand tanning behavior among adolescents, we conducted a systematic review of the literature to identify correlates of intentional tanning in the United States. We included articles on original research published in English between January 1, 2001, and October 31, 2011, that used self-reported data on intentional tanning by U.S. adolescents aged 8 to 18 years and examined potential correlates of tanning behaviors. Thirteen articles met our criteria; all used cross-sectional survey data and quantitative methods to assess correlates of intentional tanning. Results indicate that multiple factors influence tanning among adolescents. Individual factors that correlated with intentional tanning include demographic factors (female sex, older age), attitudes (preferring tanned skin), and behaviors (participating in other risky or appearance-focused behaviors such as dieting). Social factors correlated with intentional tanning include parental influence (having a parent who tans or permits tanning) and peer influence (having friends who tan). Only four studies examined broad contextual factors such as indoor tanning laws and geographic characteristics; they found that proximity to tanning facilities and geographic characteristics (living in the Midwest or South, living in a low ultraviolet area, and attending a rural high school) are associated with intentional tanning. These findings inform future public health research and intervention efforts to reduce intentional tanning.


Aptamer-functionalized nanoparticles for surface immobilization-free electrochemical detection of cortisol in a microfluidic device.
Monitoring the periodic diurnal variations in cortisol from small volume samples of serum or saliva is of great interest, due to the regulatory role of cortisol within various physiological functions and stress symptoms. Current detection assays are immunologically based and require cumbersome antibody immobilization chemistries, thereby limiting the assay versatility, kinetics, and reproducibility. We present a quantitative aptamer-based detection methodology for cortisol that does not require target labeling, capture probe immobilization on the detection surface or wash steps prior to readout. Using a recognition system of aptamer functionalized gold nanoparticles pre-bound with electro-active triamcinolone, the cortisol level is detected based on its competitive binding to the aptamer by following signal from the displaced triamcinolone using square wave voltammetry at patterned graphene-modified electrodes in a microfluidic or nanoslit device. Due to the 3D analyte diffusion profile at the aptamer interface and the ability to enhance the surface area for cortisol capture, this assay shows signal linearity over a five-log analyte concentration range (10 μg/mL to 30 pg/mL) and exhibits rapid binding kinetics with cortisol versus other glucocorticoids, as apparent from the absence of interferences from estradiol, testosterone and progesterone. The assay is carried out within the biologically relevant range for glucocorticoids in serum and saliva matrices, and benchmarked versus ELISA and radioimmunoassays. Based on absence of cumbersome surface immobilization and wash steps for carrying out this assay, its quantitative signal characteristics and its ability to resist interferences from other glucocorticoids, we envision its application towards routine monitoring of cortisol within bio-fluids.


Serum creatinine predicts success in retrograde ureteral stent placement in patients with pelvic malignancies.
To evaluate serum hemoglobin, baseline serum creatinine, serum creatinine at the diagnosis of obstructive hydronephrosis, and the increase in serum creatinine greater than baseline to predict for success in retrograde ureteral stent placement in patients with pelvic malignancies. In a retrospective chart review, we identified 57 patients at our institution with obstructive hydronephrosis secondary to pelvic malignancies in which retrograde ureteral stent placement was attempted from January 2002 to May 2005. The patient charts were reviewed for the baseline serum creatinine, preoperative serum creatinine and hemoglobin, and serum creatinine at presentation of obstructive hydronephrosis. This population was divided into group 1 (n = 31, 54%), in which retrograde stent placement was successful, and group 2 (n = 26, 46%), in which stent placement failed and subsequent percutaneous nephrostomy tube placement was required. The Student t test was used to determine whether a significant difference existed between the two groups for each laboratory parameter. The serum hemoglobin and baseline creatinine were not significantly different between the two groups and could not be used to predict for the success or failure of stent placement (P = 0.10 and P = 0.59, respectively). However, the average serum creatinine at presentation of obstructive hydronephrosis was significantly different between group 1 (2.4 +/- 1.4 ng/dL) and group 2 (5.3 +/- 6.3; P = 0.014), as was an increase in serum creatinine greater than baseline (P = 0.002). The results of this study have shown that the serum creatinine level at the presentation of obstructive hydronephrosis can be used to predict for success in retrograde ureteral stent placement in patients with pelvic malignancies.


The Novel Organic Emitters for High-Performance Narrow-Band Deep Blue OLEDs.
Narrow-band deep-blue organic light-emitting diodes (OLEDs) have played a key role in the field of high-quality full-color displays. However, because of the considerable challenges of inherent band gaps, unbalanced carrier injection and the lack of molecular structures, narrow-band deep-blue emitters develop slowly compared with red- and green-emitting materials. Encouragingly, with the continuous efforts of scientists in recent years, great progress has been made in the molecule design and material synthesis of highly efficient narrow-band deep-blue emitters. The typical deep-blue emitters which exhibit narrow emission with a full width at half maximum of < 50 nm are summarized in this article. They are divided into the three categories: fluorescence, phosphorescence and thermally activated delayed fluorescence. The methods of molecular design for realizing narrow-band deep-blue emission are described in detail and future research directions are also discussed in this article.


Back to Fundamentals: Using High- and Low-Fidelity Simulation to Provide Reinforcement of Preventative Measures for Sepsis.
Health care-associated infections result in a staggering number of preventable patient deaths per year. Numerous point-of-practice initiatives and action plans have been implemented, requiring ongoing and continuing education for practicing clinicians. Equally important is the implementation of prevention practices and protocols throughout programs responsible for preparing health care providers. The use of simulation as an experiential form of learning is effective in nursing education as fundamental concepts and best practices in sepsis prevention are repeated and reinforced.


A patch of positively charged residues regulates the efficacy of clinical DR5 antibodies in solid tumors.
Receptor clustering is the first and critical step to activate apoptosis by death receptor-5 (DR5). The recent discovery of the autoinhibitory DR5 ectodomain has challenged the long-standing view of its mechanistic activation by the natural ligand Apo2L. Because the autoinhibitory residues have remained unknown, here we characterize a crucial patch of positively charged residues (PPCR) in the highly variable domain of DR5. The PPCR electrostatically separates DR5 receptors to autoinhibit their clustering in the absence of ligand and antibody binding. Mutational substitution and antibody-mediated PPCR interference resulted in increased apoptotic cytotoxic function. A dually specific antibody that enables sustained tampering with PPCR function exceptionally enhanced DR5 clustering and apoptotic activation and distinctively improved the survival of animals bearing aggressive metastatic and recurrent tumors, whereas clinically tested DR5 antibodies without PPCR blockade function were largely ineffective. Our study provides mechanistic insights into DR5 activation and a therapeutic analytical design for potential clinical success.


Face-mask-aware Facial Expression Recognition based on Face Parsing and Vision Transformer.
As wearing face masks is becoming an embedded practice due to the COVID-19 pandemic, facial expression recognition (FER) that takes face masks into account is now a problem that needs to be solved. In this paper, we propose a face parsing and vision Transformer-based method to improve the accuracy of face-mask-aware FER. First, in order to improve the precision of distinguishing the unobstructed facial region as well as those parts of the face covered by a mask, we re-train a face-mask-aware face parsing model, based on the existing face parsing dataset automatically relabeled with a face mask and pixel label. Second, we propose a vision Transformer with a cross attention mechanism-based FER classifier, capable of taking both occluded and non-occluded facial regions into account and reweigh these two parts automatically to get the best facial expression recognition performance. The proposed method outperforms existing state-of-the-art face-mask-aware FER methods, as well as other occlusion-aware FER methods, on two datasets that contain three kinds of emotions (M-LFW-FER and M-KDDI-FER datasets) and two datasets that contain seven kinds of emotions (M-FER-2013 and M-CK+ datasets).


Factors in choosing atypical antipsychotics: toward understanding the bases of physicians' prescribing decisions.
Off-label prescribing of medications, polypharmacy, and other questionable prescribing practices have led investigators to examine a large VA pharmacy database to determine if physician prescribing decisions appear reasonable. The current study addresses the question of physician prescribing of atypical antipsychotics in 34,925 veterans with schizophrenia, using a series of signal detection analyses. These results suggest that only three factors (hospital size, age, and secondary diagnosis) allow classification of patients prescribed atypicals into three groups with frequencies of use of atypicals ranging from 43% to 79%, and that these results are consistent with reasonable clinical practice. Results of two-stage signal detection analyses are readily interpretable by clinicians and administrators who are faced with the task of evaluating how physicians prescribe medications in clinical practice. Physicians' decisions to prescribe atypical antipsychotics are based on both patient and fiscal considerations. This likely reflects a combination of clinical judgment and institutional guidelines.


Factors associated with professional mental health service use among adults with suicidal ideation.
The uptake of professional mental health services among people with suicidal ideation remains low, yet few community-based studies have characterised modifiable individual barriers to service use. Our aims were (1) to identify factors associated with use of professional mental health services among people experiencing suicidal ideation, and (2) to distinguish subgroups with varying levels of service use. 1462 Australian adults (78.8% female) were recruited online to participate in a cross-sectional survey. Logistic regression analysis was used to identify factors associated with professional service use. A decision tree model was used to identify subgroups with varying rates of professional service use. Most participants (62%) had used professional services for mental health concerns in the past 12 months. Greater rates of service use were observed in participants who were middle aged, spoke English, disclosed to informal sources or helplines, met criteria for a mental health disorder, had higher levels of entrapment, psychological distress, and disinhibition, and lower levels of detachment and antagonism. At the terminal nodes of the decision tree analysis, service use ranged from 21% to 94%. The most important determinants of service use were meeting criteria for a mental disorder and disclosure of suicidal ideation to family/friends and helplines. These findings suggest that interventions to support the safe disclosure of suicidal ideation may assist in increasing service use. There is also the need for services that meet the needs of individuals who do not meet criteria for a mental health condition.


Lymphangiogenesis and lymph node metastasis in breast cancer.
There have been few studies on lymphangiogenesis in the past due to the lack of specific lymphatic endothelial markers, and lymphatic-specific growth factors. Recently, these limitations have been relieved by the discovery of a small number of potential lymphatic-specific markers. The relationship between lymphangiogenesis and regional or distant metastasis has not previously been investigated in humans. Using these lymphatic markers, it is possible to explore the relationship between lymphangiogenesis and tumour metastasis. This study indirectly quantified lymphangiogenesis by measuring mRNA expression of all seven lymphatic markers described above in breast cancers and correlated these markers with lymphatic involvement and survival. The cDNA from 153 frozen archived breast samples were analysed with Q-PCR for all seven lymphangiogenic markers. This was correlated with various prognostic factors as well as patient survival. There was significantly greater expression of all 7 markers in malignant compared to benign breast tissue. In addition, there was greater expression in lymph node positive/grade 3 tumours when compared to lymph node negative/grade 1 tumours. In 5 of the markers, there was a greater expression in poor NPI prognostic tumours when compared to favourable prognostic tumours which was not statistically significant. There was no association between recurrence risk and lymphangiogenic marker expression. In summary, the findings from this study show that lymphangiogenesis, measured by specific lymphatic marker expression, is higher in breast cancers than in normal breast tissue. Secondly, breast cancers which have metastasised to the regional lymphatics show higher expression compared to those which have not, although the individual differences for all five markers were not statistically significant.


Phacocryolysis and phacoemulsification.
The effect of rapid freezing and thawing was tested in vitro on 100 human hard nuclear cataracts before ultrasonic emulsification. After phacocryolysis the interspace between lens fibers increased, and the normally closely packed fibers appeared to loosen. This seemed to soften the hard cataract, thereby facilitating ultrasonic emulsification.


The performance of duplex ultrasonography for the assessment of renal artery stenosis in Takayasu's arteritis patients.
This study intends to analyze the hemodynamic parameters of the renal artery in patients with Takayasu's arteritis (TAK) to explore the diagnostic efficacy of duplex ultrasonography in assessing the involved renal artery in TAK patients. One hundred fifteen TAK patients with 314 renal arteries were retrospectively analyzed, who were admitted to Peking Union Medical College Hospital between 2017 and 2022. These patients underwent both renal artery ultrasonography and angiography within a 4-week period. Specifically, the study compared seven ultrasonic parameters across groups categorized by the severity of renal artery stenosis (RAS), including noninvolvement, < 50% stenosis, 50-69% stenosis, and 70-99% stenosis. Receiver operating characteristic (ROC) curves were employed to determine the optimal threshold values for renal artery peak systolic velocity (RPSV), renal-aortic PSV ratio (RAR), and renal-interlobar PSV ratio (RIR) in order to diagnose various degrees of RAS in TAK patients. Statistically significant differences were observed in RAR and RIR among the four groups (all P < 0.05). However, no statistically significant differences were found in RPSV and AT between the moderate stenosis group (50-69% stenosis) and the severe stenosis group (70-99% stenosis). The discrimination of interlobar PSV (IPSV) and interlobar RI (IRI) was not significant, and IEDV did not show statistical significance among the four groups. For TAK patients, the recommended thresholds of RPSV for the diagnosis of renal artery involvement (RAI), ≥ 50% RAS, and ≥ 70% RAS were determined to be 143 cm/s, 152 cm/s, and 183 cm/s, respectively. The sensitivities, specificities, and accuracies of these thresholds were all found to be greater than 80%. Additionally, the optimal thresholds of RIR for detecting RAI, ≥ 50% RAS, and ≥ 70% RAS were determined to be 4.6, 5.6, and 6.4, respectively, with satisfactory diagnostic efficiencies. The areas under the curve (AUCs) for RPSV and RIR were calculated to be 0.908 and 0.910, respectively, for the diagnosis of ≥ 50% RAS, and 0.876 and 0.882 for the diagnosis of ≥ 70% RAS. When the aortic PSV is greater than or equal to 140 cm/s, the RAR exhibits inadequate diagnostic efficacy. Conversely, when the aortic PSV is less than 140 cm/s, a RAR value of 2.2 or higher can be employed as the diagnostic threshold for identifying RAS of 70% or greater, with a sensitivity of 84.00%, specificity of 89.93%, and an overall accuracy of 89.08%. In the present study, it has been demonstrated that RPSV and RIR possess substantial diagnostic value as ultrasonic parameters for diagnosing RAS in TAK patients. Furthermore, when assessing the diagnostic efficacy of RAR, it is crucial to consider the severity of aortic stenosis as a determining factor.


Non-anemic iron deficiency, oral iron supplementation, and oxidative damage in college-aged females.
Oxidative damage, as indicated by protein carbonyl and lipid hydroperoxide concentrations, was assessed in the plasma of college-aged females with adequate iron status and with non-anemic iron deficiency before and after eight weeks of iron supplementation. At baseline, the mean serum ferritin, iron, transferrin saturation, and total iron binding capacity of the iron deficient group (n = 13) was significantly different from the iron adequate controls (n = 24). Mean plasma lipid hydroperoxide and protein carbonyl concentrations did not differ between groups at baseline. Following eight weeks of iron supplementation, the mean serum ferritin, iron, and transferrin saturation significantly increased and the total iron binding capacity significantly decreased in the iron deficient group. No significant differences in plasma lipid hydroperoxide or protein carbonyl concentrations were found between groups at the end of the study period. When plasma lipid hydroperoxide and protein carbonyl concentrations of subjects within groups were compared at the start versus at the end of the study, no significant differences were found for either group. Neither non-anemic iron deficiency nor its treatment with oral iron supplements is associated with oxidative damage in the plasma of college-aged females.


Glucose transporters in cardiovascular system in health and disease.
Glucose transporters are essential for the heart to sustain its function. Due to its nature as a high energy-consuming organ, the heart needs to catabolize a huge quantity of metabolic substrates. For optimized energy production, the healthy heart constantly switches between various metabolites in accordance with substrate availability and hormonal status. This metabolic flexibility is essential for the maintenance of cardiac function. Glucose is part of the main substrates catabolized by the heart and its use is fine-tuned via complex molecular mechanisms that include the regulation of the glucose transporters GLUTs, mainly GLUT4 and GLUT1. Besides GLUTs, glucose can also be transported by cotransporters of the sodium-glucose cotransporter (SGLT) (SLC5 gene) family, in which SGLT1 and SMIT1 were shown to be expressed in the heart. This SGLT-mediated uptake does not seem to be directly linked to energy production but is rather associated with intracellular signalling triggering important processes such as the production of reactive oxygen species. Glucose transport is markedly affected in cardiac diseases such as cardiac hypertrophy, diabetic cardiomyopathy and heart failure. These alterations are not only fingerprints of these diseases but are involved in their onset and progression. The present review will depict the importance of glucose transport in healthy and diseased heart, as well as proposed therapies targeting glucose transporters.


Inhibition of in vitro lymphocyte blastogenesis by chicken alpha-fetoprotein.
Chicken alpha-fetoprotein (ch-AFP), purified from fetal chicken serum and embryo extracts, respectively, was examined for its immunomodulatory effect in vitro. Significant (P less than 0.05) suppression of the allogeneic mixed lymphocyte reaction (MLR) was observed, when these preparations were added to one-way mixed lymphocyte cultures (MLC) in quantities of 62.5-1000 micrograms/ml. Suppression of the MLR was depending on the presence of ch-AFP for at least 16 h after initiation of the MLC, suggesting that this fetal protein was acting mainly in the early phase of lymphoblastogenesis. Serum of chicken embryos (12th and 15th day of incubation), day-old chickens, and of 10-week-old chickens of four different inbred lines were also found to exert suppression of the MLR. From these data, it is hypothesized that ch-AFP plays an immunoregulatory role by maintaining a certain stage of self tolerance during differentiation of the avian immune system.