Hepatitis-associated antigen hepatitis. An electron microscopic study of virus-like particles in liver cells.
Light and electron microscopic examinations were carried out on liver tissues from 6 renal transplant recipients who developed Australia antigen-associated hepatitis, referred to in this paper as hepatitis-associated antigen (HAA) hepatitis. While under immunosuppressive therapy, the patients showed rapid progression of acute hepatitis to chronic active hepatitis and posthepatitic cirrhosis resulting in liver failure. By electron microscopy, in 5 of 6 patients, characteristic virus-like particles of 230 A size were observed in massive numbers in the nucleus and occasionally in the cytoplasm of liver cells. No similar particles were found in liver biopsies from other patients. These particles had an appearance of nucleocapsid without an outer coat, and were believed to be the viruses in their natural infective states. The predominantly intranuclear location of the particles and the associated nuclear changes suggested that the nucleus is the primary site of virus replication. The finding of the virus-like particles is believed to be diagnostic for HAA hepatitis. While HAA is implicated in serum hepatitis, the identification of HAA with the virus-like particles of this study is still to be established. In the phagosomes, there were some particles showing an outer membrane and a tail-like structure. Both the coated and the noncoated particles were believed to be the same virus. The phagosomes also contained what appeared to be "degradated" viral material. The lysosomal activity in the infected hepatitic cells seemed to be increased. This study showed nonspecific changes of the liver cell nuclei and organelles, probably related to viral infection. The precise mechanism of cell injury remains to be elucidated. However, the result of this study has provided a reasonable basis for future investigations of HAA hepatitis.


Lumbar spinal fusion in the outpatient setting: an update on management, surgical approaches and planning.
Outpatient lumbar spinal fusion surgery has the potential for improved patient satisfaction, speed of recovery, and economic advantages when compared to inpatient surgery. Despite the rise in the number of these procedures performed annually, the literature on this topic remains scarce. As such, there is a need for a comprehensive review of current concepts in indications and management. The current review will present the most recent literature regarding pre-operative, intra-operative, and post-operative considerations when performing outpatient lumbar spinal fusion surgery.


Rate of Perceived Exertion and Cardiorespiratory Fitness in Older Adults with and without Alzheimer's Disease.
Exercise has many benefits for physical and cognitive health in older adults, yet there are many barriers to exercise adherence in this population. Subjective perception of exercise difficulty, or rate of perceived exertion (RPE), may especially be a barrier to exercise in individuals with Alzheimer's disease (AD), due to changes in initiation and motivation that accompany changes in cognition and brain function. RPE is the most commonly used measure of subjective effort in exercise research, yet the relationship between RPE and objective fitness is not fully understood in older adults. A better understanding is needed to support initiation, engagement, and maintenance of exercise and determine the appropriateness for use of RPE as a measure in this population. Our study aimed to 1) evaluate the degree to which objective measures of cardiorespiratory fitness correlates with the most commonly used subjective measure of effort, RPE and 2) examine any difference in the relationship between objective cardiorespiratory fitness and RPE between individuals with and without AD. We explored these relationships during a graded exercise test. Objective fitness and subjective effort were negatively associated. Independent of cardiorespiratory fitness, older age, female gender, cognitive impairment, and use of heart medications predicted greater self-reported effort during exercise. Results are discussed in terms of social psychological phenomena and potential neuropsychological deficits leading to increased subjective feelings of effort. These findings establish that the RPE measure may not be appropriate and may even detract from effort during graded exercise testing among older adults with AD.


["We eat in this way because…". Understanding eating behaviors of Chilean women of low socioeconomic status].
The prevalence of obesity is higher in women than in men, especially in those of lower socioeconomic status. It is established that this group tends to have a less healthy diet. To explore the eating behaviors of low-income Chilean women. Semi-structured interviews with photo-elicitation were conducted with 31 Chilean women aged 36 ± 6 years, who lived with a partner and had at least one sibling under 12 years of age. The interviews were transcribed and an inductive analysis of the participants' discourses was made. Seven themes were described in relation to their influence on three eating behaviors (food purchase, preparation and intake): Family, preferences, temporality, financial issues, special occasions, perceptions about food, and availability of food. The family exerted a strong influence on the behaviors and had an impact on the other themes encountered. Eating behaviors were influenced by several factors, both at the personal and environment levels. These factors interacted with each other to produce different forms of behavior modulation. It is therefore problematic to promote healthy eating behaviors while not considering all the influences on this behavior.


Tumor formation following murine neural precursor cell transplantation in a rat peripheral nerve injury model.
Neural stem cells show a remarkable aptitude for integration and appropriate differentiation at sites of cellular injury in central nervous system (CNS) disease models. In contrast, reports of neural stem cell applications in peripheral nerve injury models are sparse. In this study we sought to determine if the C17.2 cell line would respond to cues in the microenvironment of the injured peripheral nerve and enhance neuronal regeneration in rodent sciatic nerve injury models. We transplanted C17.2 into several sciatic nerve injury models in 45 nude rats, including nerve transection, nerve crush, and nerve gap models. Twelve of the animals in this study developed large tumors at the site of neural stem cell transplants. Histologically, the tumors resembled neuroblastomas. The tumors were confirmed to be of transplanted cell origin by positive beta-galactosidase staining. Tumors occurred only in models where the nerve remained intact or where continuity of the nerve was restored. We concluded that C17.2 transplantation into peripheral nerve injury models resulted in a high rate of tumor formation. This study demonstrates that the success of neural precursor transplants in the CNS cannot necessarily be extrapolated to the peripheral nervous system.


Investigating the prevalence of hypertension and its associated risk factors in a population-based study: Fasa PERSIAN COHORT data.
A high prevalence rate of hypertension (HTN) and its subsequent serious complications made this disease a major health-treatment concern in many societies. The current study aimed to investigate the prevalence of hypertension and its associated risk factors in Fasa PERSIAN COHORT in south of Iran in 2019. This was an analytical-cross sectional study. The study population were the individuals covered by Fasa cohort. Information of the first phase of Fasa Persian cohort in south of Iran was used in this study. Independent t test, chi-square test, analysis of variances, Pearson correlation coefficient, and multiple stepwise regression were used to analyze the obtained data. Thereafter, the data was analyzed using SPSS software version 22, and P value < 0.05 was considered as statistically significant. Out of 10,111 individuals included in the study, 5546 (54.86%) subjects were women and 4565 (45.16%) other were men. The overall prevalence rate of hypertension was estimated as 46.6%. In the present study, (16/1%) of the participants were with HTN stage 1, and (17/9%) of them were with HTN stage 2. The results show that there were significant positive correlations among HTN and age, BMI, HDL, TG, BUN, ALP, smoking, physical activity, cardiovascular diseases, diabetes, and renal failure (P < 0.5). Prevalence of HTN in this study population is considerable. Therefore, it is suggested that health system should program some plans to prevent hypertension's prevalence and eliminate its risk factors.


RanGTP-regulated interactions of CRM1 with nucleoporins and a shuttling DEAD-box helicase.
CRM1 is an export receptor mediating rapid nuclear exit of proteins and RNAs to the cytoplasm. CRM1 export cargoes include proteins with a leucine-rich nuclear export signal (NES) that bind directly to CRM1 in a trimeric complex with RanGTP. Using a quantitative CRM1-NES cargo binding assay, significant differences in affinity for CRM1 among natural NESs are demonstrated, suggesting that the steady-state nucleocytoplasmic distribution of shuttling proteins could be determined by the relative strengths of their NESs. We also show that a trimeric CRM1-NES-RanGTP complex is disassembled by RanBP1 in the presence of RanGAP, even though RanBP1 itself contains a leucine-rich NES. Selection of CRM1-binding proteins from Xenopus egg extract leads to the identification of an NES-containing DEAD-box helicase, An3, that continuously shuttles between the nucleus and the cytoplasm. In addition, we identify the Xenopus homologue of the nucleoporin CAN/Nup214 as a RanGTP- and NES cargo-specific binding site for CRM1, suggesting that this nucleoporin plays a role in export complex disassembly and/or CRM1 recycling.


Soft particle clogging in two-dimensional hoppers.
We study the outflow of soft particles through quasi-two-dimensional hoppers with both experiments and simulations. The experiments utilize spheres made with hydrogel, silicone rubber, and glass. The hopper chamber has an adjustable exit width and tilt angle (the latter to control the magnitude of gravitational forcing). Our simulation mimics the experiments using purely two-dimensional soft particles with viscous interactions but no friction. Results from both simulations and experiments demonstrate that clogging is easier for reduced gravitational force or stiffer particles. For particles with low or no friction, the average number of particles in a clogging arch depends only on the ratio between hopper exit width and the mean particle diameter. In contrast, for the silicone rubber particles with larger frictional interactions, arches have more particles than the low friction cases. Additionally, an analysis of the number of particles left in the hopper when clogging occurs provides evidence for a hydrostatic pressure effect that is relevant for the clogging of soft particles, but less so for the harder (glass) or frictional (silicone rubber) particles.


Peroxymonosulfate activation by tea residue biochar loaded with Fe3O4 for the degradation of tetracycline hydrochloride: performance and reaction mechanism.
The recycling of agricultural and food waste is an effective way to reduce resource waste and ameliorate the shortage of natural resources. The treatment of antibiotic wastewater is a current research hotspot. In this study, waste tea residue was used as a raw material to prepare biochar (T-BC) and loaded with Fe3O4 as a catalyst to activate peroxymonosulfate (PMS) for oxidative degradation of tetracycline hydrochloride (TCH). Analysis techniques such as BET, SEM, XRD, FT-IR, XPS and VSM indicated that the heterogeneous catalyst (Fe3O4@T-BC) with good surface properties and magnetic properties was successfully prepared. The results of batch-scale experiments illustrated that when the dose of the Fe3O4@T-BC catalyst was 1 g L-1, the concentration of PMS was 1 g L-1, and the initial pH was 7, the degradation rate of TCH with a concentration of 50 mg L-1 reached 97.89% after 60 minutes of reaction. When the initial pH was 11, the degradation rate of TCH reached 99.86%. After the catalyst was recycled four times using an external magnet, the degradation rate of TCH could still reach 71.32%. The data of removal of TCH could be best fitted by a pseudo-first-order model. The analysis of the degradation mechanism through a free radical quenching experiment and EPR analysis, as well as the exploration of TCH intermediate products and reaction paths through the LC-MS method, all confirmed that the Fe3O4@T-BC prepared by this method is expected to become a cost-effective and environmentally friendly heterogeneous catalyst for activating persulfate degradation of tetracycline antibiotics.


Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes.
In patients with acute coronary syndromes, it is desirable to identify a sensitive serum marker that is closely related to the degree of myocardial damage, provides prognostic information, and can be measured rapidly. We studied the prognostic value of cardiac troponin I levels in patients with unstable angina or non-Q-wave myocardial infarction. In a multicenter study, blood specimens from 1404 symptomatic patients were analyzed for cardiac troponin I, a serum marker not detected in the blood of healthy persons. The relation between mortality at 42 days and the level of cardiac troponin I in the specimen obtained on enrollment was determined both before and after adjustment for baseline characteristics. The mortality rate at 42 days was significantly higher in the 573 patients with cardiac troponin I levels of at least 0.4 ng per milliliter (21 deaths, or 3.7 percent) than in the 831 patients with cardiac troponin I levels below 0.4 ng per milliliter (8 deaths, or 1.0 percent; P < 0.001). There were statistically significant increases in mortality with increasing levels of cardiac troponin I (P < 0.001). Each increase of 1 ng per milliliter in the cardiac troponin I level was associated with a significant increase (P = 0.03) in the risk ratio for death after adjustment for the base-line characteristics that were independently predictive of mortality (ST-segment depression and age > or = 65 years). In patients with acute coronary syndromes, cardiac troponin I levels provide useful prognostic information and permit the early identification of patients with an increased risk of death.


Glandular Crowdings in Endometrial Polyps: Clinical Follow-Up and Possible Worrisome Features.
Interpretation of changes and premalignant lesions in endometrial polyps can be challenging. We evaluated the clinical course of patients with focal gland crowdings in endometrial polyps via repeat biopsies and searched for possible morphological findings in the initial biopsy that may foresee a premalignant course. Specimens diagnosed as endometrial polyp and focal gland crowding in patients who had a repeat biopsy in a 1-year period were reexamined. Morphological findings in the initial biopsies were recorded. The group whose repeat biopsies were "premalignant or malignant" (Group 1), and the group with "benign" repeat biopsies (Group 2) were compared. "Endometrial polyp and gland crowdings" was diagnosed in 115 specimens of which 38 patients had repeat biopsies. Among these 8 (21%) were diagnosed as "endometrial intraepithelial neoplasia (EIN)" (Group 1) and 30 (79%) as "benign" (Group 2). Morphological features in the initial biopsies were evaluated; PAX2 loss was 6 of 8 (75%) for Group 1 and 7 of 30 (23%) for Group 2 (P = .020), and altered epithelial cytological features were present in 5 of 8 (62%) versus 4 of 30 (13%) (P = .015), both significantly higher in Group 1. Dark intraluminal secretion, intraluminal histiocytes, intraglandular epithelial proliferation, and mean diameter of crowded gland areas were not statistically different between the 2 groups. "Focal gland crowdings" in endometrial polyps do carry a risk of EIN in subsequent biopsies. We suggest that the loss/decrease of PAX2 and altered epithelial cytological features in these areas in the initial biopsy are indicative of a premalignant course.


Rapid 90Sr/90Y determination in water samples using a sequential injection method
We have developed a semiautomatic procedure based on a sequential injection method for 90Sr/90Y determination that allows their radiochemical separation in about 30 min. The method has been tested using 90Sr/90Y solutions with activities lower than 12 Bq. The source is eluted in a pH = 6.5 medium through a MnO2-impregnated cotton filter, where 9OY is preconcentrated in preference by adsorption. 90Y is extracted from the column with hydroxylamine, some 90Sr in the leached solution has also been found. After the radiochemical separation, the total beta-activity of the leached solution has been determined using a low background alpha-beta proportional counter and, assuming the presence of 90Sr and 90Y at t = 0, the solution of the Bateman equations allows the initial concentration of both isotopes to be obtained. We have verified that the addition of some ions usually found in water samples (Cl-, HCO3-, NO3-, SO4(2-), Ca2+, Mg2+) does not interfere with the yield of the radiochemical process, (90 +/- 10)%. The method has been applied to 90Sr/90Y determination in mineral waters, and even in thermal waters, where the salt concentration can be about 3500 mg/l, the radiochemical yield remains greater than 80%.


Serological evidence of hantavirus infection in apparently healthy people from rural and slum communities in southern Chile.
Hantavirus disease in America has been recognizable because of its rapid progression in clinical cases, occurrence in previously healthy young adults, and high case fatality rate. Hantavirus disease has been proposed now to define the diversity of clinical manifestations. Since 1995, a total of 902 cases of hantavirus pulmonary syndrome have been reported in Chile, caused by Andes virus (ANDV), with overall fatality of 32%. This report describes the sero-epidemiology of hantavirus in apparently healthy people in rural and urban slum communities from southern Chile. Ten of 934 samples yielded a positive result resulting in a seroprevalence of 1.07% (95% confidence intervals: 0.05%-2.0%). A higher proportion of positive samples was found among individuals from rural villages (1.3%) and slums (1.5%) compared with farms (0.5%). Seropositivity was associated with age (p = 0.011), low education level (p = 0.006) and occupations linked to the household (homemaker, retired, or student) (p = 0.016). No evidence of infection was found in 38 sigmodontinae rodents trapped in the peri-domestic environment. Our findings highlight that exposure risk was associated with less documented risk factors, such as women in slum and rural villages, and the occurrence of infection that may have presented as flu-like illness that did not require medical attention or was misdiagnosed.


[Continuing education, motivation for cost control, a Swiss experiment].
The article reviews the prospective, controlled experience of the introduction of a physician network service (health maintenance organisation 5000 insured persons). There was a reduction of cost (26%-33%) compared with the control group, without loss of quality. This reduction still holds good after four years. Risk selection explains only a small part of the reduction in cost. The only interventions consisted of gatekeeping plus continuing medical education (CME). Diagnosis and financial data were not available and profiling was not used to control the experience. CME was provided by a quality circle once a week. In these meetings, the subjective and objective features particular to outpatient medicine were addressed.


Sex-differentiated and growth-hormone-regulated mitoinhibition in rat liver during treatment with 2-acetylaminofluorene and partial hepatectomy in the resistant hepatocyte model.
The previously observed sex difference in the growth rate of enzyme-altered foci (male greater than female) in rats treated according to the resistant hepatocyte model (RH model) occurs during selection/promotion of diethylnitrosamine-initiated cells with dietary 2-acetylaminofluorene (2-AAF) and partial hepatectomy (PH). The secretory pattern of growth hormone (GH) is sex dependent in the adult rat and is a major determinant for sex-differentiated liver functions. In the present study the capacity for liver regeneration following PH in the RH model was studied in rats of both sexes, in castrated males and in males receiving GH infusion, both treatments leading to a feminine pattern of GH secretion. Mitoinhibition during treatment with 2-AAF was shown to be more pronounced in liver from male than from female rats, both in initiated and non-initiated animals. Castration of male rats and continuous infusion of GH to males during the selection period, previously shown to decrease the focal growth rate towards that in female rats, 'feminized' also the degree of mitoinhibition. Autoradiography of sections from animals receiving continuous infusion of [3H]thymidine for 1 week, starting at the time of PH, demonstrated a lower labeling index in surrounding liver from male rats treated in the RH model than in surrounding liver from female rats. Males treated with continuous infusion of human GH during 2-AAF/PH treatment had an intermediary labeling index in the surrounding tissue. No differences in labeling index in enzyme-altered foci was observed between males, females or males plus hGH. These findings support the concept that sex-differentiated promotion in the RH model is exerted by selective mitoinhibition and that this feature is regulated by GH.


Nuclear import and export functions in the different isoforms of the AUF1/heterogeneous nuclear ribonucleoprotein protein family.
The heterogeneous nuclear ribonucleoprotein D family of proteins also known as AUF1 consists of four isoforms implicated in both nuclear and cytoplasmic functions. The AUF1 proteins are largely nuclear but also are found in the cytoplasm and are thought to undergo nucleocytoplasmic shuttling. The nucleocytoplasmic distribution and potential shuttling activity of the individual AUF1 isoforms have not been previously studied in detail. Therefore, we characterized the nucleocytoplasmic transport of each of the heterogeneous nuclear ribonucleoprotein D/AUF1 isoforms. All four AUF1 proteins were found to undergo rapid nucleocytoplasmic shuttling in a manner that is transcription-independent, carrier-mediated, and energy-requiring. Nucleocytoplasmic shuttling of the AUF1 proteins is shown to utilize a novel arrangement of nuclear import and export signals. Mutagenesis of the AUF1 proteins and fusion of polypeptides to a green fluorescent protein reporter demonstrated that a nuclear import signal is located in the C-terminal domain of the protein and is found only in the two smaller isoforms. Further mapping demonstrated that nuclear export is facilitated by sequences in AUF1 exon 7 found in the C-terminal domain of the two larger AUF1 isoforms. A subset of AUF1 proteins are shown to directly interact in vitro using purified recombinant proteins and in vivo in the absence of RNA. These results suggest that nuclear import of AUF1 is facilitated by sequences found only in the two smaller isoforms and that nuclear export is facilitated by sequences (exon 7 and the C-terminal domain) found only in the two larger isoforms. This novel arrangement of signals might represent a mechanism to assure co-shuttling of a subset of AUF1 proteins that interact in a heterocomplex.


Behavioural effects of psychoactive pharmaceutical exposure on European perch (Perca fluviatilis) in a multi-stressor environment.
With the ability to resist biodegradation and exert therapeutic effects at low concentrations, pharmaceutical contaminants have become environmental stressors for wildlife. One such contaminant is the anxiolytic oxazepam, a psychoactive pharmaceutical that is frequently detected in surface waters globally. Despite growing interest in understanding how wildlife respond to anxiolytics, synergistic effects of pharmaceuticals and other abiotic (e.g. temperature) and biotic (e.g. predation risk) stressors remain unclear. Here, using a multi-stressor approach, we investigated effects of 7-day oxazepam exposure (6.5 μg/L) on anxiety-related behaviours in juvenile European perch (Perca fluviatilis). The multi-stressor approach was achieved by exposing perch to oxazepam at two temperatures (10 °C and 18 °C), and at two predation risk regimes-generated using chemical cues from the northern pike (Esox lucius). Our exposures resulted in a successful uptake of the drug from the water, i.e., oxazepam was measured in perch muscle tissue at 50 ± 17 ng/g (mean ± SD). We found significant oxazepam-induced effects on boldness, with 76.7% of the treated fish entering the white background (i.e. 'exposed' area where exposure to presumed risks are higher) within the first 5 min, compared to 66.6% of the control fish. We also found a significant effect of temperature on total time spent freezing (i.e. staying motionless). Specifically, fish in the low temperature treatments (oxazepam, predation) froze for longer than fish in high temperatures. Our multi-stressor study is the first to uncover how anxiety-related behaviours in wild juvenile fish are altered by changes in water temperature and perceived predation risk. Importantly, our findings highlight the need to focus on multiple stressors to improve understanding of how organisms not only survive, but adapt to, human-induced environmental change.


Evolving medicinal chemistry strategies in antibiotic discovery.
Chemical modification of synthetic or natural product antibiotic scaffolds to expand potency and spectrum and to bypass mechanisms of resistance has dominated antibiotic drug discovery and proven immensely successful. However, the inexorable evolution of drug resistance coupled with a drought in innovation in antibiotic discovery contribute to a dearth of new drugs entering to market. Better understanding of the physicochemical properties of antibiotic chemical space is required to inform new antibiotic discovery. Innovations such as the development of antibiotic adjuvants to preserve efficacy of existing drugs together with expanding antibiotic chemical diversity through synthetic biology or new techniques to mine antibiotic producing organisms, are required to bridge the growing gap between the need for new drugs and their discovery.


Incidence and nature of the most common rugby injuries sustained in Argentina (1991-1997).
To study the incidence of the most commonly sustained injuries in Argentine rugby and analyse them according to type, position and age of the players, and phase and time of play. A prospective registry of injuries was constructed in different provincial unions of Argentina. Data were collected during a whole weekend each year from 1991 to 1997. Chi2 with Yates correction test, contingency tables, odds ratios (OR), and 95% confidence intervals (CI) were calculated (Epi Info Version 6.04a). A total of 924 injuries were registered in 1296 rugby games, involving 38 933 players. The mean (SD) incidence per weekend was 2.4 (0.2)% (95% CI 2.22 to 2.53), and the number of injuries per season was 24,188. Overall, senior players suffered more injuries than those in younger divisions (OR = 1.53; 95% CI 1.34 to 1.76; p<0.0001). The most common type of injury was pulled muscles of the lower limbs (11.7%, p<0.0001). Overall, the knee was the most susceptible to injury (14.1%, p<0.0001). Senior players suffered more pulled muscles of the lower limbs (OR = 2.99; 95% CI 2.01 to 4.46; p<0.0001), ankle ligament distension (OR = 1.69; 95% CI 1.12 to 2.53; p = 0.01), knee trauma (OR = 1.69; 95% CI 1.06 to 2.68; p = 0.02), bleeding wounds on the face (OR = 3.86; 95% CI 2.24 to 6.70; p<0.0001), and knee ligament distension (OR = 2.14; 95% CI 1.16 to 3.96; p = 0.01). Younger players had a greater risk of suffering muscular or ligament injuries of the cervical column (OR = 3.0; 95% CI 1.05 to 10.08; p = 0.04). The forwards had a higher risk of injury (OR = 1.41; 95% CI 1.23 to 1.61; p<0.0001). The most commonly injured player was the flanker (15.5%, p<0.01), and the most common mechanism was in open play (33%). More injuries were sustained in the second half (OR = 1.17; 95% CI 1.03 to 1.34; p = 0.01). Injuries are the cause of significant morbidity among rugby players in Argentina. A more thorough investigation and a greater understanding of the mechanisms are crucial in order to update the rugby laws and reduce this high injury incidence.


Sensory nerve pathology in multifocal motor neuropathy.
The nosological status of multifocal motor neuropathy remains controversial. The clinical and electrodiagnostic hallmarks suggest selective motor fiber involvement. In this study, we asked to what extent sensory nerves might be involved pathologically in multifocal motor neuropathy. Examination of sensory nerve biopsy specimens from 11 patients did reveal pathological findings in all, but they were very mild. An increased number of thinly myelinated, large-caliber fibers was the unifying feature common to each specimen. By electron microscopy, each biopsy specimen had thinly myelinated fibers surrounded by minor onion bulbs. Active demyelination, though scant, was seen in 3 nerves. Myelinated fiber density was normal. Subperineurial edema and inflammation were not present. We conclude that multifocal motor neuropathy is not an exclusively motor abnormality, although it appears to be so clinically and electrophysiologically. The frequent, albeit mild, pathological abnormalities in sensory fibers suggest that the demyelinating pathophysiology also affects sensory fibers, but to a lesser degree than motor fibers. Some investigators maintain that multifocal motor neuropathy is within the spectrum of chronic inflammatory demyelinating polyneuropathy. The very mild degree of sensory fiber involvement, the absence of inflammation or edema, and the distinctive clinical features support the concept of multifocal motor neuropathy as distinct from chronic inflammatory demyelinating polyneuropathy.


Intralesional therapy for advanced melanoma: promise and limitation.
Patients with unresectable, multiple or advanced locally/regionally metastatic stage IIIB/C or stage IV M1a melanoma have a high risk for recurrence, progression and metastasis. The article reviews treatment advances for this population. After promising phase 2 results with Allovectin-7 (velimogene aliplasmid), overall survival in a phase 3 study was shorter for Allovectin-7 than for dacarbazine/temozolomide (median 18.8 versus 24.1 months).In a phase 2 trial of intratumoral electroporation of plasmid interleukin-12 among 28 patients with advanced melanoma, the primary endpoint of best overall response rate within 24 weeks of first treatment was 32.2% for objective response and 10.7% for complete response.In the phase 3 OPTiM trial of talimogene laherparepvec, the intralesional agent that is furthest along in clinical testing, the primary endpoint of durable response rate was 16% for talimogene laherparepvec and 2% for granulocyte macrophage colony-stimulating factor.In the PV-10 phase 2 trial among 80 patients with stage III-IV melanoma, the overall response rate was 51%, with a 26% complete response rate. Despite advances, many patients will need several lines of therapy. Some will not be eligible for systemic therapy. Their low toxicity, easy administration and likely systemic immune effects make intralesional therapies an attractive option.


Regulating the Regulators: Recent Revelations in the Control of E3 Ubiquitin Ligases.
Since its discovery as a post-translational signal for protein degradation, our understanding of ubiquitin (Ub) has vastly evolved. Today, we recognize that the role of Ub signaling is expansive and encompasses diverse processes including cell division, the DNA damage response, cellular immune signaling, and even organismal development. With such a wide range of functions comes a wide range of regulatory mechanisms that control the activity of the ubiquitylation machinery. Ub attachment to substrates occurs through the sequential action of three classes of enzymes, E1s, E2s, and E3s. In humans, there are 2 E1s, ∼ 35 E2s, and hundreds of E3s that work to attach Ub to thousands of cellular substrates. Regulation of ubiquitylation can occur at each stage of the stepwise Ub transfer process, and substrates can also impact their own modification. Recent studies have revealed elegant mechanisms that have evolved to control the activity of the enzymes involved. In this minireview, we highlight recent discoveries that define some of the various mechanisms by which the activities of E3-Ub ligases are regulated.


Renal expression of FGF23 and peripheral resistance to elevated FGF23 in rodent models of polycystic kidney disease.
Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis and is linked to cardiovascular disease and all-cause mortality in chronic kidney disease. FGF23 rises in patients with CKD stages 2-3, but in patients with autosomal dominant polycystic kidney disease, the increase of FGF23 precedes the first measurable decline in renal function. The mechanisms governing FGF23 production and effects in kidney disease are largely unknown. Here we studied the relation between FGF23 and mineral homeostasis in two animal models of PKD. Plasma FGF23 levels were increased 10-fold in 4-week-old cy/+ Han:SPRD rats, whereas plasma urea and creatinine concentrations were similar to controls. Plasma calcium and phosphate levels as well as TmP/GFR were similar in PKD and control rats at all time points examined. Expression and activity of renal phosphate transporters, the vitamin D3-metabolizing enzymes, and the FGF23 co-ligand Klotho in the kidney were similar in PKD and control rats through 8 weeks of age, indicating resistance to FGF23, although phosphorylation of the FGF receptor substrate 2α protein was enhanced. In the kidneys of rats with PKD, FGF23 mRNA was highly expressed and FGF23 protein was detected in cells lining renal cysts. FGF23 expression in bone and spleen was similar in control rats and rats with PKD. Similarly, in an inducible Pkd1 knockout mouse model, plasma FGF23 levels were elevated, FGF23 was expressed in kidneys, but renal phosphate excretion was normal. Thus, the polycystic kidney produces FGF23 but is resistant to its action.


Massage therapy reduces anxiety and enhances EEG pattern of alertness and math computations.
Twenty-six adults were given a chair massage and 24 control group adults were asked to relax in the massage chair for 15 minutes, two times per week for five weeks. On the first and last days of the study they were monitored for EEG, before, during and after the sessions. In addition, before and after the sessions they performed math computations, they completed POMS Depression and State Anxiety Scales and they provided a saliva sample for cortisol. At the beginning of the sessions they completed Life Events, Job Stress and Chronic POMS Depression Scales. Group by repeated measures and post hoc analyses revealed the following: 1) frontal delta power increased for both groups, suggesting relaxation; 2) the massage group showed decreased frontal alpha and beta power (suggesting enhanced alertness); while the control group showed increased alpha and beta power; 3) the massage group showed increased speed and accuracy on math computations while the control group did not change; 4) anxiety levels were lower following the massage but not the control sessions, although mood state was less depressed following both the massage and control sessions; 5) salivary cortisol levels were lower following the massage but not the control sessions but only on the first day; and 6) at the end of the 5 week period depression scores were lower for both groups but job stress score were lower only for the massage group.


Adherence of Internet-Based Cancer Risk Assessment Tools to Best Practices in Risk Communication: Content Analysis.
Internet-based risk assessment tools offer a potential avenue for people to learn about their cancer risk and adopt risk-reducing behaviors. However, little is known about whether internet-based risk assessment tools adhere to scientific evidence for what constitutes good risk communication strategies. Furthermore, their quality may vary from a user experience perspective. This study aims to understand the extent to which current best practices in risk communication have been applied to internet-based cancer risk assessment tools. We conducted a search on August 6, 2019, to identify websites that provided personalized assessments of cancer risk or the likelihood of developing cancer. Each website (N=39) was coded according to standardized criteria and focused on 3 categories: general website characteristics, accessibility and credibility, and risk communication formats and strategies. Some best practices in risk communication were more frequently adhered to by websites. First, we found that undefined medical terminology was widespread, impeding comprehension for those with limited health literacy. For example, 90% (35/39) of websites included technical language that the general public may find difficult to understand, yet only 23% (9/39) indicated that medical professionals were their intended audience. Second, websites lacked sufficient information for users to determine the credibility of the risk assessment, making it difficult to judge the scientific validity of their risk. For instance, only 59% (23/39) of websites referenced the scientific model used to calculate the user's cancer risk. Third, practices known to foster unbiased risk comprehension, such as adding qualitative labels to quantitative numbers, were used by only 15% (6/39) of websites. Limitations in risk communication strategies used by internet-based cancer risk assessment tools were common. By observing best practices, these tools could limit confusion and cultivate understanding to help people make informed decisions and motivate people to engage in risk-reducing behaviors.


Television food advertising to children: a global perspective.
We compared television food advertising to children in several countries. We undertook a collaboration among 13 research groups in Australia, Asia, Western Europe, and North and South America. Each group recorded programming for 2 weekdays and 2 weekend days between 6:00 and 22:00, for the 3 channels most watched by children, between October 2007 and March 2008. We classified food advertisements as core (nutrient dense, low in energy), noncore (high in undesirable nutrients or energy, as defined by dietary standards), or miscellaneous. We also categorized thematic content (promotional characters and premiums). Food advertisements composed 11% to 29% of advertisements. Noncore foods were featured in 53% to 87% of food advertisements, and the rate of noncore food advertising was higher during children's peak viewing times. Most food advertisements containing persuasive marketing were for noncore products. Across all sampled countries, children were exposed to high volumes of television advertising for unhealthy foods, featuring child-oriented persuasive techniques. Because of the proven connections between food advertising, preferences, and consumption, our findings lend support to calls for regulation of food advertising during children's peak viewing times.


A clinician's guide to the use of lung volume reduction surgery.
The primary purpose of the National Emphysema Treatment Trial (NETT) was to evaluate the clinical efficacy of lung volume reduction surgery (LVRS) compared with medical therapy as a treatment for advanced emphysema. Transitioning the results of a complex multicenter long-term clinical trial into routine clinical practice is challenging, particularly when the therapy examined is controversial, as was the case in NETT. Aspects of the "clinical art" used by the study investigators to select and treat patients are not always transparent to practitioners reading study publications. At the last NETT Steering Committee meeting, a roundtable discussion was held with investigators, coordinators, Steering Committee leadership, and Data Coordinating Center staff regarding the clinical aspects of patient evaluation and selection and performance of LVRS in advanced emphysema. The questions posed to the meeting participants were ones that are commonly asked by patients and their treating physicians who are considering LVRS and included the following: Why recommend LVRS to a patient? When should LVRS be recommended to a patient? What types of patients are candidates for LVRS? What are the important barriers to performing LVRS? What are the major messages delivered by NETT? It is hoped that answers from NETT investigators to some of these commonly encountered questions will provide clarity and guidance to clinicians faced with the responsibility of considering and discussing LVRS with their patients. NETT investigators were also queried regarding the future directions of research in emphysema and the role that NETT played in shaping that future. The following article is a summary of the highlights of these discussions.


[Methods of inversion closure of transient colostomy].
The method of inversive excision of colostomy, securing access to noninflamed tissues of intestine and pericolostomic region for consequent suturing made in accordance to requirements. While using the method purulent-inflammatory complications had occurred in less than 5% of patients and insufficiency of anastomotic sutures--in 3.4%.


Aversion and proneness to shame in self- and informant-reported personality disorder symptoms.
The present study examined the specificity and extent of relationships between shame and symptoms of five personality disorders (PDs), as they are apparent to both the self and others. Borderline, narcissistic, avoidant, dependent, and obsessive-compulsive PD symptoms were assessed in a sample of 367 undergraduates that evidenced a wide range of symptom levels (25.6% endorsed threshold or greater severity of symptoms on the Schedule of Nonadaptive and Adaptive Personality-2). Importantly, for both conceptual and methodological reasons, information about PD symptoms was also obtained from friends/family of 45.2% of the sample. Shame aversion (the tendency to perceive shame as a particularly painful and unwanted emotion) was assessed using the Shame-Aversive Reactions Questionnaire, and shame-proneness (the propensity to experience shame across situations) was assessed using the Test of Self-Conscious Affect-3. Shame aversion displayed the most consistent relationship with PD symptoms, being associated with self-reports of symptoms of all five PDs and informant-reports of symptoms of three PDs, over and above experiential avoidance, trait affect, and guilt. A significant Shame Aversion × Shame-Proneness interaction further revealed that shame-proneness was associated with symptoms of avoidant and dependent PDs among individuals with high but not low levels of shame aversion. Thus, these findings highlight shame aversion's specific importance in PD symptoms and suggest important future research directions.


Mental Health Issues and Complex Experiences of Abuse Among Trans and Gender Diverse Young People: Findings from Trans Pathways.
Purpose: Trans and gender diverse (TGD) young people have reported high levels of mental distress in research studies, specifically depression, anxiety, self-harming, and suicidal behaviors. Rates of abuse are also high in TGD populations, but little is known about how this relates to mental health in populations of TGD young people. This study sought to examine associations between experiences of abuse and mental health outcomes. Methods: A cross-sectional study design was used. An anonymous online questionnaire was conducted to determine rates of abuse among Australian TGD young people (N = 859) and the potential association with poor mental health. Primary outcomes of interest were self-reported psychiatric diagnoses, self-harm and suicidal behaviors, and current anxiety and depressive symptoms. Results: Exposures to six forms of abuse are reported in this article: extrafamilial physical abuse, familial physical abuse, extrafamilial sexual abuse, familial sexual abuse, abuse within an intimate relationship, and other familial abuse (including emotional or verbal abuse and neglect). All six forms of abuse measured were associated with poor mental health overall; risk estimates for some forms of abuse were much stronger than others. Conclusion: The current findings have wide-ranging implications for clinical practice. Those working in TGD health care need to be aware of the high prevalence of violence and abuse among TGD young people and the association with poor mental health outcomes. The findings also have implications for broader societal change and interventions targeting increasing parental support to reduce familial violence against TGD young people.


The retinoid X receptor agonist bexarotene relieves positive symptoms of schizophrenia: a 6-week, randomized, double-blind, placebo-controlled multicenter trial.
The limitations of antipsychotic therapy in schizophrenia and schizoaffective disorder led to the investigation of the putative utility of pharmacologic augmentation strategies. The antitumor agent bexarotene via nuclear retinoid X receptor (RXR) activation might modulate numerous metabolic pathways involved in the pathogenesis of schizophrenia and schizoaffective disorder. This trial aimed to investigate efficacy and safety of add-on bexarotene to ongoing antipsychotic treatment of patients with schizophrenia or schizoaffective disorder. Ninety inpatients and outpatients that met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder participated in a 6-week, double-blind, randomized, placebo-controlled multicenter study. Bexarotene (75 mg/d) was added to ongoing antipsychotic treatment from October 2008 to December 2010. The reduction in the severity of symptoms on the Positive and Negative Syndrome Scale (PANSS) was a primary outcome. Secondary outcomes included general functioning, quality of life, and side effect scales. Seventy-nine participants (88%) completed the protocol. Controlling for antipsychotic agents, a mixed model showed that patients who received adjunctive bexarotene had significantly lower PANSS positive scale scores compared to patients who received placebo (F = 8.6, P = .003; treatment arms × time, F = 2.7, P = .049), with moderate effect size (d = 0.48; 95% CI,0.04-0.93). Patients with mean or higher baseline PANSS positive scale scores and patients who did not take lipid-reducing agents revealed greater amelioration of positive symptoms (F = 7.4, P = .008). Other symptoms and secondary outcome measures were not affected by adjunctive bexarotene. Bexarotene was well tolerated, though 2 reversible side effects were reported: a significant increase in total cholesterol levels (P < .001) and a decrease in total thyroxine levels (P < .001). Bexarotene might potentially be a novel adjuvant therapeutic strategy for schizophrenia, particularly for the reduction of positive symptoms. The potential benefits and risks of ongoing administration of bexarotene warrant further evaluation. ClinicalTrials.gov identifier: NCT00535574.


Predictors of Changes in Smoking From Third Trimester to 9 Months Postpartum.
While much has been written about postpartum smoking relapse prevention, few have examined changes in smoking behavior from pregnancy (third trimester) through 9 months postpartum among pregnant smokers, particularly for the large number of women who decrease tobacco consumption during pregnancy but do not quit altogether. Data were obtained from 168 women who smoked during their pregnancy. Women were followed longitudinally from their first prenatal appointment through 9 months postpartum. Maternal substance use was assessed using the Timeline Followback and verified by maternal salivary analyses. Breastfeeding, other substance use, and partner smoking were assessed through maternal interviews at each time point and were considered as potential predictors of change in smoking. Women returned to more than half of their levels of preconception tobacco consumption by 9 months postpartum. There was one significant predictor of changes in smoking patterns pregnancy to postpartum. Women who breastfed their infants for at least 90 days smoked far less postpartum than women who breastfed for a short time or did not breastfeed at all. As noted in previous research of pregnant quitters, postpartum relapse prevention or harm reduction interventions should ideally be timed early in the postpartum period. Additionally, promoting breastfeeding among pregnant smokers and supporting women through at least 3 months of breastfeeding may be beneficial to such interventions.


Age-related changes in sleep/wake patterns among Korean teenagers.
As children go through the transition from childhood to adolescence, many shifts occur in sleep/wake patterns related to intrinsic and extrinsic developmental changes. These shifts have been shown to result in corresponding shifts in sleep phase (later sleep onset) and sleep deprivation among teenagers in Western societies. However, the effect of these developmental changes on the sleep habits of Korean teenagers has not been analyzed. This study aims to quantify age-related changes in sleep/wake patterns among Korean teenagers and elucidate cultural and other factors causing these changes. The School Sleep Habits Survey was administered in homeroom classes to students in grades 5 to 12 (mean age: 13.7 +/- 2.4 years) selected via a 2-way stratification sampling method. The survey included items regarding usual sleep/wake patterns over the previous 2 weeks as well as measures of daytime sleepiness, sleep/wake-problem behavior, depressed mood, and morningness/eveningness. A total of 1457 students (52.9% male) completed the survey. The higher the grade, the later bedtime was found to be on both school days and weekends. There was a similar relationship between increasing grade and earlier wake time on school days, but higher grades were associated with later wake time on weekends. Total sleep time decreased by approximately 3 hours on school nights and 1 hour on weekend nights from grades 5 to 12. Adolescents were severely sleep deprived, with mean school-night total sleep times of 6.02, 5.62, and 4.86 hours for 10th-, 11th-, and 12th-graders, respectively. In the higher grades, there was a greater discrepancy between school nights and weekends in terms of bedtime and wake time, and the magnitude of weekend oversleep increased. Older students also reported more daytime sleepiness, more sleep/wake-problem behavior, more depressed mood, and more eveningness preference. The chief reasons students cited for their sleep deprivation differed across grades: Academic demands and entertainment (such as Internet and television) were reported by 5th- and 6th-graders, entertainment and then academic demands by 7th-, 8th-, and 9th-graders, and early school start time and academic demands by 10th-, 11th- and 12th-graders. This study clearly demonstrates that Korean adolescents do not get adequate sleep and that they have profound discrepancies in their sleep/wake patterns between school and weekend nights. Compared with previous studies from other countries, Korean students display even greater sleep deprivation and also more irregular sleep/wake patterns. This study also demonstrates that academic demands/stress and early school start time are the most important contributing factors for sleep deprivation among Korean adolescents. These findings stress the need to promote awareness of the magnitude of adolescent sleep deprivation and its detrimental effects in Korean society.


Diagnosis of alpha thalassemia in the newborn. Cord blood survey utilizing gene mapping.
Application of the technique of gene mapping has made possible accurate assessment of the alpha thalassemia defect in cord blood samples obtained in a Sydney teaching hospital. Results showed a 5.2% incidence of the alpha+ thalassemia haplotype in the population being tested. Various hematological parameters such as hemoglobin, mean corpuscular hemoglobin, hemoglobin EPG pattern at pH 8.9 and the percentage of hemoglobin Bart's determined by elution at pH 6.7 were measured to assess which would be the most useful in diagnosis of alpha thalassemia at this time of life. The most consistent test proved to be hemoglobin EPG pattern at pH 8.9, and reasons for this are discussed.


[Local recurrence of Castleman disease].
A rare case of recurrent Castleman disease is reported. A 49-year-old man was referred to our division under the suspicion of mediastinal tumor. We performed tumor resection successfully, and the tumor was shown to be Castleman disease by histology. The patient had a past history of this disease, therefore it was suggested that the tumor recurred at the same site 20-years after removal.


[Complications of therapeutic embolization of juvenile angiofibroma of the nasopharynx].
We report two cases of major complications in therapeutic embolization of juvenile angiofibromas. We discuss no permanent and major complications of this procedure. A brief review of this illness is also presented.


Tripartite Symbiosis of an Anaerobic Scuticociliate with Two Hydrogenosome-Associated Endosymbionts, a Holospora-Related Alphaproteobacterium and a Methanogenic Archaeon.
A number of anaerobic ciliates, unicellular eukaryotes, intracellularly possess methanogenic archaea and bacteria as symbiotic partners. Although this tripartite relationship is of interest in terms of the fact that each participant is from a different domain, the difficulty in culture and maintenance of those host species with symbiotic partners has disturbed both ecological and functional studies so far. In this study, we obtained a stable culture of a small anaerobic scuticociliate, strain GW7. By transmission electron microscopic observation and fluorescent in situ hybridization with domain-specific probes, we demonstrate that GW7 possesses both archaeal and bacterial endosymbionts in its cytoplasm. These endosymbionts are in dependently associated with hydrogenosomes, which are organelle producing hydrogen and ATP under anaerobic conditions. Clone library analyses targeting prokaryotic 16S rRNA genes, fluorescent in situ hybridization with endosymbiont-specific probes, and molecular phylogenetic analyses revealed the phylogenetic affiliations and intracellular localizations of these endosymbionts. The endosymbiotic archaeon is a methanogen belonging to the genus Methanoregula (order Methanomicrobiales); a member of this genus has previously been described as the endosymbiont of an anaerobic ciliate from the genus Metopus (class Armophorea), which is only distantly related to strain GW7 (class Oligohymenophorea). The endosymbiotic bacterium belongs to the family Holosporaceae of the class Alphaproteobacteria, which also comprises several endosymbionts of various aerobic ciliates. For this endosymbiotic bacterium, we propose a novel candidate genus and species, "Candidatus Hydrogenosomobacter endosymbioticus."IMPORTANCE Tripartite symbioses between anaerobic ciliated protists and their intracellular archaeal and bacterial symbionts are not uncommon, but most reports have been based mainly on microscopic observations. Deeper insights into the function, ecology, and evolution of these fascinating symbioses involving partners from all three domains of life have been hampered by the difficulties of culturing anaerobic ciliates in the laboratory and the frequent loss of their prokaryotic partners during long-term cultivation. In the present study, we report the isolation of an anaerobic scuticociliate, strain GW7, which has been stably maintained in our laboratory for more than 3 years without losing either of its endosymbionts. Unexpectedly, molecular characterization of the endosymbionts revealed that the bacterial partner of GW7 is phylogenetically related to intranuclear endosymbionts of aerobic ciliates. This strain will enable future genomic, transcriptomic, and proteomic analyses of the interactions in this tripartite symbiosis and a comparison with endosymbioses in aerobic ciliates.


Effects of human lymphoblastoid interferon on proliferation, gene expression and tumourigenicity of human hepatoma cell lines.
Hep G2 and Hep 3B cells, two human hepatoma cell lines, showed decreased thymidine (Thd) incorporation into intracellular acid-insoluble pools when exposed to Wellferon, human lymphoblastoid interferon (IFN). Inhibition was maximal after 48 h treatment with Wellferon and was reversible. Significant inhibition in Wellferon-treated Hep 3B cells was noted at concentrations of 1 IFN unit/ml, which was over 1000-fold less than that required to produce equivalent effects in Hep G2 cells. The decrease in Thd incorporation into acid-insoluble pools was due to both alterations in Thd anabolism and a small but significant decrease in incorporation into DNA with no apparent effect on nucleoside transport. The small but significant Wellferon-induced decrease in Thd incorporation into DNA was reflected in a small but significant decrease in cell proliferation in both cell lines. In addition, Wellferon induced a decrease in the steady-state level of c-myc- and P450-specific RNA transcripts but did not affect the steady-state levels of transforming growth factor-B, fos, N-Ras, or erb-B RNA transcripts. These Wellferon effects, however, did not result in any significant antitumour effects when Hep 3B or Hep G2 cells were grown in athymic nude mice treated intraperitoneally with 8 mu/kg/day Wellferon. Wellferon can induce an antiviral state in both cell lines using Semliki Forest virus and Herpes simplex virus as viral challenges. Taken collectively, these data indicate that Wellferon produces both antiviral and slight but significant antiproliferative effects in Hep G2 and Hep 3B cells, but does not produce significant antitumor effects in vivo using these cell lines in nude mice xenografts.


Xiro, a Xenopus homolog of the Drosophila Iroquois complex genes, controls development at the neural plate.
The Drosophila homeoproteins Ara and Caup are members of a combination of factors (prepattern) that control the highly localized expression of the proneural genes achaete and scute. We have identified two Xenopus homologs of ara and caup, Xiro1 and Xiro2. Similarly to their Drosophila counterparts, they control the expression of proneural genes and, probably as a consequence, the size of the neural plate. Moreover, Xiro1 and Xiro2 are themselves controlled by noggin and retinoic acid and, similarly to ara and caup, they are overexpressed by expression in Xenopus embryos of the Drosophila cubitus interruptus gene. These and other findings suggest the conservation of at least part of the genetic cascade that regulates proneural genes, and the existence in vertebrates of a prepattern of factors important to control the differentiation of the neural plate.


Nutrient and Mineral Compositions of Wild Leafy Vegetables of the Karen and Lawa Communities in Thailand.
Wild food plants are commonly used in the traditional diets of indigenous people in many parts of the world, including northern Thailand. The potential contribution of wild food plants to the nutrition of the Karen and Lawa communities remains poorly understood. Wild food plants, with a focus on leafy vegetables, were ranked by the Cultural Food Significance Index (CFSI) based on semi-structured interviews. Twelve wild plant species were highly mentioned and widely consumed. The importance of the wild vegetables was mainly related to taste, availability, and multifunctionality of the species. Their contents of proximate and minerals (P, K, Na, Ca, Mg, Fe, Mn, Zn, and Cu) were analyzed using standard methods. The proximate contents were comparable to most domesticated vegetables. The contents of Mg (104 mg/100 g FW), Fe (11 mg/100 g FW), and Zn (19 mg/100 g FW) in the wild leafy vegetables were high enough to cover the daily recommended dietary allowances of adults (19-50 years), whereas a few species showed Mn contents higher than the tolerable upper intake level (>11 mg/100 g edible part). The wild leafy vegetables, therefore, are good sources of minerals and we recommend their continued usage by indigenous people. Further research on these wild leafy vegetables' contents of antioxidants, vitamins, heavy metals, anti-nutrient factors, and food safety is recommended.


Current treatment options for management of anal intraepithelial neoplasia.
Anal squamous cell cancer is an uncommon malignancy caused by infection with oncogenic strains of Human papilloma virus. Anal cancer is much more common in immunocompromised persons, including those infected with Human immunodeficiency virus. High-grade anal intraepithelial neoplasia (HGAIN), the precursor of anal cancer, is identified by clinicians providing care for patients with anorectal disease, and is increasingly being identified during screening of immunosuppressed patients for anal dysplasia. The traditional treatment for HGAIN has been excision of macroscopic disease with margins. This approach is effective for patients with small unifocal HGAIN lesions. Patients with extensive multifocal HGAIN frequently have recurrence of HGAIN after excision, and may have postoperative complications of anal stenosis or fecal incontinence. This led to the suggestion by some that treatment for HGAIN should be delayed until patients developed anal cancer. Alternative approaches in identification and treatment have been developed to treat patients with multifocal or extensive HGAIN lesions. High-resolution anoscopy combines magnification with anoscopy and is being used to identify HGAIN and determine treatment margins. HGAIN can then be ablated with a number of modalities, including infrared coagulation, CO2 laser, and electrocautery. These methods for HGAIN ablation can be performed with local anesthesia on outpatients and are relatively well tolerated. High-resolution anoscopy-directed HGAIN ablation is evolving into a standard approach for initial treatment and then subsequent monitoring of a disease which should be expected to be recurrent. Another treatment approach for HGAIN is topical treatment, principally with 5-fluorouracil or imiquimod. Topical therapies have the advantage of being nonsurgical and are well suited for treating widespread multifocal disease. Topical treatments have the disadvantage of requiring extended treatment courses and causing a symptomatic inflammatory response. Successful treatment requires adherence to a regime that is uncomfortable at best and at worst painful. Topical treatments can be successful in motivated adherent patients willing to accept these side effects.


Obesity and essential hypertension. Hemodynamics, intravascular volume, sodium excretion, and plasma renin activity.
Systemic hemodynamics, intravascular volume, and plasma renin activity were determined in 135 lean, midly obese, or distinctly overweight subjects who were normotensive or had borderline or established essential hypertension. Cardiac output (but not index) was higher and peripheral resistance lower in obese than in lean subjects, except in borderline hypertension. Intravascular volume was increased in obese patients, and more so when corrected for body height; correction for body weight led to relative volume contraction. Intravascular volume correlated directly with cardiac output in the entire population, as well as in the subgroups. Intravascular volume correlated inversely with total peripheral resistance in all subjects and in each subgroup. Both correlations remained significant when an approximation was used to correct influences of obesity on total blood volume. Sodium excretion was higher in obese than in lean subjects. Thus, despite the expanded intravascular volume in obesity, the pathophysiologic relationship between systemic hemodynamics and intravascular volumes remains unchanged. Relatively low peripheral resistance in obesity may decrease the risk of systemic vascular disease. Nevertheless, since circulating volume is increased, the greater venous return adds an additional load to a left ventricle that is already burdened by a high afterload caused by arterial hypertension.


Phototoxicity of 7-oxycoumarins with keratinocytes in culture.
Seventy-one 7-oxycoumarins, 66 synthesized and 5 commercially sourced, were tested for their ability to inhibit growth in murine PAM212 keratinocytes. Forty-nine compounds from the library demonstrated light-induced lethality. None was toxic in the absence of UVA light. Structure-activity correlations indicate that the ability of the compounds to inhibit cell growth was dependent not only on their physiochemical characteristics, but also on their ability to absorb UVA light. Relative lipophilicity was an important factor as was electron density in the pyrone ring. Coumarins with electron withdrawing moieties - cyano and fluoro at C3 - were considerably less active while those with bromines or iodine at that location displayed enhanced activity. Coumarins that were found to inhibit keratinocyte growth were also tested for photo-induced DNA plasmid nicking. A concentration-dependent alteration in migration on neutral gels caused by nicking was observed.


Multimodal therapy for category III chronic prostatitis/chronic pelvic pain syndrome in UPOINTS phenotyped patients.
The complex network of etiological factors, signals and tissue responses involved in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) cannot be successfully targeted by a single therapeutic agent. Multimodal approaches to the therapy of CP/CPPS have been and are currently being tested, as in the frame of complex diagnostic-therapeutic phenotypic approaches such as the urinary, psychosocial, organ-specific, infection, neurological and muscle tenderness (UPOINTS) system. In this study, the effect of combination therapy on 914 patients diagnosed, phenotyped and treated in a single specialized prostatitis clinic was analyzed. Patients received α-blockers, Serenoa repens (S. repens) extracts combined or not with supplements (lycopene and selenium) and, in the presence of documented or highly suspected infection, antibacterial agents. Combination treatment induced marked and significant improvements of National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) prostatitis symptom scores, International Index of Erectile Function (IIEF) sexual dysfunction scores, urinary peak flow rates and bladder voiding efficiency. These improvements, assessed after a 6-month course of therapy, were sustained throughout a follow-up period of 18 months. A clinically appreciable reduction of ≥6 points of the total NIH-CPSI score was achieved in 77.5% of patients subjected to combination therapy for a period of 6 months. When the patients were divided in two cohorts, depending on the diagnosis of CP/CPPS [inflammatory (IIIa) vs. non-inflammatory (IIIb) subtypes], significant improvements of all signs and symptoms of the syndrome were observed in both cohorts at the end of therapy. Intergroup comparison showed that patients affected by the IIIa sub-category of CP/CPPS showed more severe signs and symptoms (NIH-CPSI total, pain and quality of life impact scores, and Qmax) at baseline when compared with IIIb patients. However, the improvement of symptoms after therapy was significantly more pronounced in IIIa patients when compared with IIIb patients. In contrast to current opinion, the evidence emerging from the present investigation suggests that the inflammatory and non-inflammatory sub-categories of CP/CPPS may represent two distinct pathological conditions or, alternatively, two different stages of the same condition. In conclusion, a simple protocol based on α-blockers, S. repens extracts and supplements and antibacterial agents, targeting the urinary, organ specific and infection domains of UPOINTS, may induce a clinically appreciable improvement of the signs and symptoms of CP/CPPS in a considerable percentage of patients. In patients not responding sufficiently to such therapy, second-line agents (antidepressants, anxiolytics, muscle relaxants, 5-phosphodiesterase inhibitors and others) may be administered in order to achieve a satisfactory therapeutic response.


Host-based ribavirin resistance influences hepatitis C virus replication and treatment response.
Many individuals infected with hepatitis C virus (HCV) develop a chronic infection, and of those who are treated with pegylated interferon and ribavirin (RBV), many do not respond. While the nucleoside analog RBV improves treatment outcome, and will likely be an important component of therapy with next-generation viral inhibitors, RBV's mechanism is controversial. Most of RBV's proposed mechanisms require RBV import into cells. Therefore, we explored whether host-based RBV resistance develops through reduced cellular uptake, akin to chemotherapy resistance in some cancers. We examined the effect of host-based RBV resistance on HCV replication in cultured hepatoma Huh7.5 liver cells and whether RBV resistance develops in HCV patients. When Huh7.5 cells were exposed to RBV, resistance developed through reduced RBV uptake via the ENT1 nucleoside transporter and antiviral efficacy was reduced. The uptake defect in RBV-resistant cells was specific to RBV, since transport of another ENT1 substrate, cytidine, was unaffected. Importantly, RBV uptake significantly declined in HCV patient peripheral blood mononuclear cells (PBMCs) following 4 weeks of therapy. Furthermore, maintenance of RBV uptake correlated with rapid treatment response. Our results uncovered a novel form of antiviral drug resistance and suggest that host-based RBV resistance develops in HCV patients undergoing therapy and that maintenance of RBV uptake may contribute to rapid viral clearance.


A survey analysis of thoracic surgeons in Turkey on mediastinal investigation of lung cancer.
A total of 59 general thoracic surgeons of 21 academically based thoracic surgery centres in Turkey were surveyed to identify the attitudes toward mediastinal investigations in patients with lung cancer. The surgeons were asked 16 questions in five separate groups by survey questionnaire. Analyses of the replies were as follows: Group I: 37 (62.7%) of the respondents were working in 11 centres where > 100 patients are admitted or referred for lung cancer annually. More than 50 thoracotomies are performed for lung cancer annually in one third of the centres in which 28 (47.5%) respondents work. Group II: Among the diagnostic methods for evaluating mediastinum, surgeons most commonly used the computed tomography, mediastinoscopy, mediastinotomy and scalene lymph node biopsy. Invasive staging was done routinely by ten (16.9%) and selectively by 44 (74.6%). Group III: In patients with preoperatively histologically proven ipsilateral mediastinal lymph node involvement, 39 (66.1%) were advocates of operating. When the lymph node(s) was found to be positive at operation, 33 of them (55.9%) gave the decision with respect to the number, size and presence of pericapsular invasion of the node(s), while 24 (40.7%) decided to perform lung resection in every situation. Group IV: All accessible mediastinal nodes were said to be removed at thoracotomy by 37 (62.7%). Group V: Currently available methods for mediastinal investigation were found to be partially sufficient by 37 (62.7%). The most important factor in predicting postoperative survival was selected as nodal status by 27 (45.8%). It is noticed that nearly all thoracic surgeons in Turkey perform mediastinal investigation preoperatively in patients with lung cancer, however, the impact of lymph node status needs to be more commonly appreciated.


Protection of bats (Eptesicus fuscus) against rabies following topical or oronasal exposure to a recombinant raccoon poxvirus vaccine.
Rabies is an ancient neglected tropical disease that causes tens of thousands of human deaths and millions of cattle deaths annually. In order to develop a new vaccine for potential use in bats, a reservoir of rabies infection for humans and animals alike, an in silico antigen designer tool was used to create a mosaic glycoprotein (MoG) gene using available sequences from the rabies Phylogroup I glycoprotein. This sequence, which represents strains more likely to occur in bats, was cloned into raccoonpox virus (RCN) and the efficacy of this novel RCN-MoG vaccine was compared to RCN-G that expresses the glycoprotein gene from CVS-11 rabies or luciferase (RCN-luc, negative control) in mice and big brown bats (Eptesicus fuscus). Mice vaccinated and boosted intradermally with 1 x 107 plaque forming units (PFU) of each RCN-rabies vaccine construct developed neutralizing antibodies and survived at significantly higher rates than controls. No significant difference in antibody titers or survival was noted between rabies-vaccinated groups. Bats were vaccinated either oronasally (RCN-G, RCN-MoG) with 5x107 PFU or by topical application in glycerin jelly (RCN-MoG, dose 2x108 PFU), boosted (same dose and route) at 46 days post vaccination (dpv), and then challenged with wild-type big brown variant RABV at 65 dpv. Prior to challenge, 90% of RCN-G and 75% of RCN-MoG oronasally vaccinated bats had detectable levels of serum rabies neutralizing antibodies. Bats from the RCN-luc and topically vaccinated RCN-MoG groups did not have measurable antibody responses. The RCN-rabies constructs were highly protective and not significantly different from each other. RCN-MoG provided 100% protection (n = 9) when delivered oronasally and 83% protection (n = 6) when delivered topically; protection provided by the RCN-G construct was 70% (n = 10). All rabies-vaccinated bats survived at a significantly (P ≤ 0.02) higher rate than control bats (12%; n = 8). We have demonstrated the efficacy of a novel, in silico designed rabies MoG antigen that conferred protection from rabies challenge in mice and big brown bats in laboratory studies. With further development, topical or oronasal administration of the RCN-MoG vaccine could potentially mitigate rabies in wild bat populations, reducing spillover of this deadly disease into humans, domestic mammals, and other wildlife.


Enhanced delivery of 5-aminolevulinic acid esters by iontophoresis in vitro.
The goals of this study were to quantitatively evaluate the iontophoretic delivery of a homologous series of cationic aminolevulinic acid (ALA) esters and to determine the contributions of electromigration and electroosmosis to their overall electrotransport in vitro. Anodal iontophoretic transport of ALA esters through porcine skin in vitro was followed for 2 h at a constant current of 0.5 mA/cm2. To deduce the mechanism, the concomitant transport of an electroosmotic marker, mannitol, was also assessed. Positively charged ALA esters of moderate lipophilicity showed increased iontophoretic flux through the skin. A more than 50-fold enhancement as compared with the zwitterionic parent ALA was observed for the methyl ester. As the size and lipophilicity of the ester increased, the efficiency of electrotransport decreased. The most lipophilic esters reduced the electroosmotic flow presumably because of the association of these cations with negative charges in the skin. Iontophoresis of methyl-ALA and hexyl-ALA also increased the amount of prodrug delivered into the skin. In summary, significant topical delivery of ALA esters can be achieved by iontophoresis, and transport into and across the skin was greatly enhanced compared with that of ALA itself. It remains to be seen whether this enhanced local bioavailability of the protoporphyrin prodrug can allow improved photodynamic therapy for the treatment of skin cancer.


Perinatal high-fat diet alters development of GABAA receptor subunits in dorsal motor nucleus of vagus.
Perinatal high-fat diet (pHFD) exposure increases the inhibition of dorsal motor nucleus of the vagus (DMV) neurons, potentially contributing to the dysregulation of gastric functions. The aim of this study was to test the hypothesis that pHFD increases the inhibition of DMV neurons by disrupting GABAA receptor subunit development. In vivo gastric recordings were made from adult anesthetized Sprague-Dawley rats fed a control or pHFD (14 or 60% kcal from fat, respectively) from embryonic day 13 (E13) to postnatal day 42 (P42), and response to brainstem microinjection of benzodiazepines was assessed. Whole cell patch clamp recordings from DMV neurons assessed the functional expression of GABAA α subunits, whereas mRNA and protein expression were measured via qPCR and Western blotting, respectively. pHFD decreased basal antrum and corpus motility, whereas brainstem microinjection of L838,417 (positive allosteric modulator of α2/3 subunit-containing GABAA receptors) produced a larger decrease in gastric tone and motility. GABAergic miniature inhibitory postsynaptic currents in pHFD DMV neurons were responsive to L838,417 throughout development, unlike control DMV neurons, which were responsive only at early postnatal timepoints. Brainstem mRNA and protein expression of the GABAA α1,2, and 3 subunits, however, did not differ between control and pHFD rats. This study suggests that pHFD exposure arrests the development of synaptic GABAA α2/3 receptor subunits on DMV neurons and that functional synaptic expression is maintained into adulthood, although cellular localization may differ. The tonic activation of slower GABAA α2/3 subunit-containing receptors implies that such developmental changes may contribute to the observed decreased gastric motility. NEW & NOTEWORTHY Vagal neurocircuits involved in the control of gastric functions, satiation, and food intake are subject to significant developmental regulation postnatally, with immature GABAA receptors expressing slower α2/3-subunits, whereas mature GABAA receptor express faster α1-subunits. After perinatal high-fat diet exposure, this developmental regulation of dorsal motor nucleus of the vagus (DMV) neurons is disrupted, increasing their tonic GABAergic inhibition, decreasing efferent output, and potentially decreasing gastric motility.


Inhibition of growth and metastatic progression of pancreatic carcinoma in hamster after somatostatin receptor subtype 2 (sst2) gene expression and administration of cytotoxic somatostatin analog AN-238.
The sst2 somatostatin receptor mediates the antiproliferative effects of somatostatin analogs. The present study demonstrates that stable expression of sst2 in the hamster pancreatic cancer cells PC-1 and PC-1.0 activates an autocrine negative loop leading to an in vitro inhibition of cell proliferation. In vivo studies conducted in Syrian golden hamsters after orthotopic implantation of PC-1.0 cells showed that both tumor growth and metastatic progression of allografts containing 100% of sst2-expressing cells were significantly inhibited for up to 20 days after implantation, as compared with control allografts that did not express sst2. A local antitumor bystander effect was observed after induction of mixed tumors containing a 1:3 ratio of sst2-expressing cells to control cells. Tumor volume and incidence of metastases of mixed tumors were significantly reduced at day 13 post implantation. This effect decreased with time as at day 20, growth of mixed tumors was similar to that of control tumors. After administration of the cytotoxic somatostatin conjugate AN-238 on day 13, antitumor bystander effect observed in mixed tumors was significantly extended to day 20. We also observed that in vitro invasiveness of sst2-expressing PC-1.0 cells was significantly reduced. Tyrosine dephosphorylation of E-cadherin may participate in restoring the E-cadherin function, reducing in turn pancreatic cancer cell motility and invasiveness. This dephosphorylation depends on the tyrosine phosphatase src homology 2-containing tyrosine phosphatase 1 (SHP-1) positively coupled to sst2 receptor. The inhibitory effect of sst2 gene expression on pancreatic cancer growth and invasion combined with chemotherapy with targeted cytotoxic somatostatin analog administration provides a rationale for a therapeutic approach to gene therapy based on in vivo sst2 gene transfer.


Sex and species differences in epithelial transport in rat and mouse kidneys: Modeling and analysis.
The goal of this study was to investigate the functional implications of sex and species differences in the pattern of transporters along nephrons in the rat and mouse kidney, as reported by Veiras et al. (J Am Soc Nephrol 28: 3504-3517, 2017). To do so, we developed the first sex-specific computational models of epithelial water and solute transport along the nephrons from male and female mouse kidneys, and conducted simulations along with our published rat models. These models account for the sex differences in the abundance of apical and basolateral transporters, glomerular filtration rate, and tubular dimensions. Model simulations predict that 73% and 57% of filtered Na+ is reabsorbed by the proximal tubules of male and female rat kidneys, respectively. Due to their smaller transport area and lower NHE3 activity, the proximal tubules in the mouse kidney reabsorb a significantly smaller fraction of the filtered Na+, at 53% in male and only 34% in female. The lower proximal fractional Na+ reabsorption in female kidneys of both rat and mouse is due primarily to their smaller transport area, lower Na+/H+ exchanger activity, and lower claudin-2 abundance, culminating in significantly larger fractional delivery of water and Na+ to the downstream nephron segments in female kidneys. Conversely, the female distal nephron exhibits a higher abundance of key Na+ transporters, including Na+-Cl- cotransporters in both species, epithelial Na+ channels for the female rat, and Na+-K+-Cl-cotransporters for the female mouse. The higher abundance of transporters accounts for the enhanced water and Na+ transport along the female rat and mouse distal nephrons, relative to the respective male, resulting in similar urine excretion between the sexes. Model simulations indicate that the sex and species differences in renal transporter patterns may partially explain the experimental observation that, in response to a saline load, the diuretic and natriuretic responses were more rapid in female rats than males, but no significant sex difference was found in mice. These computational models can serve as a valuable tool for analyzing findings from experimental studies conducted in rats and mice, especially those involving genetic modifications.


Computers in clinical and laboratory diagnosis.
Even though the process of reaching a diagnosis from the available information was first described mathematically over 200 years ago, it is only recently that computers have been applied to the problem. Examples are given to the type of approach that has been used in differentiating between possible alternative causes of conditions such as jaundice or acute abdominal pain and it is shown that the computer programme can give results at least as accurate as the most skilled clinician and usually in a much shorter time. The application of computers to problems of diagnosis in histopathology is discussed and the method of cluster analysis is illustrated in relation to the differentiation between lichen planus and leukoplakia. There appears to be some possibility of identifying patients among the group with leukoplakia who were most likely to develop a carcinoma.


How to Deal With Relatives of Patients Dying in the Hospital? Qualitative Content Analysis of Relatives' Experiences.
Hospital care and communication tend to be focused on the individual patient, and decision making is typically based on the principle of individual autonomy. It can be questioned whether this approach is adequate when a patient is terminally ill. Our aim was to explore the involvement and experiences of relatives in the hospital during the patient's last phase of life. This study was embedded in a retrospective questionnaire study on the quality of dying of a consecutive sample of patients who died in a general university hospital in The Netherlands. We performed a secondary qualitative analysis of relatives' comments and answers to open questions. Relatives of 951 deceased adult patients were asked to complete a questionnaire; 451 questionnaires were returned and analyzed for this study. Relatives expressed a need for 1) comprehensible, timely, and sensitive information and communication, 2) involvement in decision making, 3) acknowledgment of their position, 4) being able to trust health care staff, and 5) rest and privacy. When relatives felt that their role had sufficiently been acknowledged by health care professionals (HCPs), their experiences were more positive. Relatives emphasized their relation with the patient and their involvement in care of the patient dying in the hospital. An approach of HCPs to care based on the concept of individual autonomy seems inadequate. The role of relatives might be better addressed by the concept of relational autonomy, which provides HCPs with opportunities to create a relationship with relatives in care that optimally addresses the needs of patients.


Survivability and proliferation of microorganisms in bentonite with implication to radioactive waste geological disposal: strong effect of temperature and negligible effect of pressure.
As bentonite hosts a diverse spectrum of indigenous microorganisms with the potential to influence the long-term stability of deep geological repositories, it is essential to understand the factors influencing microbial activity under repository conditions. Here, we focus on two factors, i.e., temperature and swelling pressure, using a suspension of Cerny Vrch bentonite to boost microbial activity and evaluate microbial response. Suspensions were exposed either to different pressures (10, 12 and 15 MPa; to simulate the effect of swelling pressure) or elevated temperatures (60, 70, 80 and 90 °C; to simulate the effect of cannister heating) for four weeks. Each treatment was followed by a period of anaerobic incubation at atmospheric pressure/laboratory temperature to assess microbial recovery after treatment. Microbial load and community structure were then estimated using molecular-genetic methods, with presence of living cells confirmed through microscopic analysis. Our study demonstrated that discrete application of pressure did not influence on overall microbial activity or proliferation, implying that pressure evolution during bentonite swelling is not the critical factor responsible for microbial suppression in saturated bentonites. However, pressure treatment caused significant shifts in microbial community structure. We also demonstrated that microbial activity decreased with increasing temperature, and that heat treatment strongly influenced bentonite microbial community structure, with several thermophilic taxa identified. A temperature of 90 °C proved to be limiting for microbial activity and proliferation in all bentonite suspensions. Our study emphasizes the crucial role of a deep understanding of microbial activity under repository-relevant conditions in identifying possible strategies to mitigate the microbial potential within the deep geological repository and increase its long-term stability and safety.


Patient satisfaction in Malaysia's busiest outpatient medical care.
This study aimed to explore factors associated with patient satisfaction of outpatient medical care in Malaysia. A cross-sectional exit survey was conducted among 340 outpatients aged between 13 and 80 years after successful clinical consultations and treatment acquirements using convenience sampling at the outpatient medical care of Tengku Ampuan Rahimah Hospital (HTAR), Malaysia, being the country's busiest medical outpatient facility. A survey that consisted of sociodemography, socioeconomic, and health characteristics and the validated Short-Form Patient Satisfaction Questionnaire (PSQ-18) scale were used. Patient satisfaction was the highest in terms of service factors or tangible priorities, particularly "technical quality" and "accessibility and convenience," but satisfaction was low in terms of service orientation of doctors, particularly the "time spent with doctor," "interpersonal manners," and "communication" during consultations. Gender, income level, and purpose of visit to the clinic were important correlates of patient satisfaction. Effort to improve service orientation among doctors through periodical professional development programs at hospital and national level is essential to boost the country's health service satisfaction.


Habitat restoration weakens negative environmental effects on telomere dynamics.
Habitat quality can have far-reaching effects on organismal fitness, an issue of concern given the current scale of habitat degradation. Many temperate upland streams have reduced nutrient levels due to human activity. Nutrient restoration confers benefits in terms of invertebrate food availability and subsequent fish growth rates. Here we test whether these mitigation measures also affect the rate of cellular ageing of the fish, measured in terms of the telomeres that cap the ends of eukaryotic chromosomes. We equally distributed Atlantic salmon eggs from the same 30 focal families into 10 human-impacted oligotrophic streams in northern Scotland. Nutrient levels in five of the streams were restored by simulating the deposition of a small number of adult Atlantic salmon Salmo salar carcasses at the end of the spawning period, while five reference streams were left as controls. Telomere lengths and expression of the telomerase reverse transcriptase (TERT) gene that may act to lengthen telomeres were then measured in the young fish when 15 months old. While TERT expression was unrelated to any of the measured variables, telomere lengths were shorter in salmon living at higher densities and in areas with a lower availability of the preferred substrate (cobbles and boulders). However, the adverse effects of these habitat features were much reduced in the streams receiving nutrients. These results suggest that adverse environmental pressures are weakened when nutrients are restored, presumably because the resulting increase in food supply reduces levels of both competition and stress.


Selecting socio-economic metrics for watershed management.
The selection of social and economic metrics to document baseline conditions and analyze the dynamic relationships between ecosystems and human communities are important decisions for scientists, managers, and watershed citizens. A large variety of social and economic data is available but these have limited use without theoretical frameworks. In this paper, several frameworks for reviewing social-ecosystem relations are offered, namely social sanctions, sense of place, civic structure, and cultural differences. Underlying all of these frameworks are attitudes, beliefs, values, and norms that affect which questions are asked and which indicators are chosen. Much work and significant challenges remain in developing a standard set of spatially based socio-economic metrics for watershed management.


Seasonal detection of atrazine and atzA in man-made waterways receiving agricultural runoff in a subtropical, semi-arid environment (Hidalgo County, Texas, USA).
Atrazine is a widely-used herbicide that can impact non-target organisms in the environment but can be biologically degraded by several types of microorganisms. In this study, the gene atzA, which encodes for the initial step in bacterially-mediated atrazine degradation, was used as an indicator of atrazine pollution in agricultural canals located in Hidalgo County, Texas, USA. The concentration of atrazine and atzA were monitored once per month for 12 months during 2010-2011. Atrazine was measured using an enzyme-linked immunosorbent assay; atzA abundance was monitored using Quantitative Polymerase Chain Reaction (Q-PCR) analyses. Abundance of atrazine and atzA were compared with rainy versus dry months and during planting versus non-planting months. Results showed that atrazine levels varied from below detection to 0.43 ppb and were not influenced by precipitation or planting season. Concentrations of the gene atzA were significantly different in rainy versus dry months; during planting versus non-planting times of the year; and in the interaction of precipitation and planting season. The highest concentration of atzA, approx. 4.57 × 108 gene copies ml-1, was detected in July 2010-a rainy, planting month in Hidalgo County, South Texas. However, atrazine was below detection during that month. We conclude that Q-PCR using atzA as an indicator gene is a potential method for monitoring low levels of atrazine pollution in environmental samples.


[The surgical treatment of the nodular goiter].
The simple nodular goiter, the etiology of which is multifactorial, encompasses the spectrum from the incidental asymptomatic small solitary nodule to the large intrathoracic goiter, causing pressure symptoms as well as cosmetic complaints. The mainstay in the diagnostic evaluation is related to functional and morphological characterization with serum TSH and (some kind of) imaging. Because malignancy is just as common in patients with a multinodular goiter as patients with a solitary nodule, the increasing use of fineneedle aspiration biopsy (cytology) is supported Its management is still the cause of considerable controversy. Prevalence of nodular goiter and results of surgical treatment in a large series of patients operated on at our center are reported. From January to December 2004, 1009 out of 1580 patients admitted to our Center underwent surgical treatment for thyroid disease. Nodular goiter accounted for 80% of the whole series. More in detail, toxic multinodular goiter was found in 13.5% of the patients, euthyroid multinodular goiter in 46.6%, single hyperplastic nodule in 2.3%, follicular lesion in 14%, Plummer's adenoma in 4.4%, relapsing goiter in 2.6% and thyroid cyst in 0.12%. Thyroid lobectomy was carried out in 20.8% of patients, while the remaining 79.2% underwent to total thyroidectomy. A carcinoma was incidentally found in 7.6% of the multinodular goiters. Surgery should be advocated for the treatment of thyroid nodules whenever a patient presents with either pressure symptoms, hyperthyroidism or follicular cytology. Serum TSH measurement, ultrasounds and fine needle aspiration cytology are the main diagnostic tools. Bilateral surgical exploration of the gland should be always carried out to assess the extension of the disease. Total or near total thyroidectomy in order to minimize the risk of recurrent nerve palsy and hypoparathyroidism represents the treatment of choice for bilateral goiter. Thyroid lobectomy with frozen section should be limited to unilateral nodular goiter.


Preventive effect of ginger (Zingiber officinale) pretreatment on renal ischemia-reperfusion in rats.
The present study examined the preventive effect of ginger against renal ischemia-reperfusion (I-R) injury. 30 adult male rats were used. The animals were allocated to five groups of 6 rats: (1) normal (N), (2) normal + ginger (N+G), (3) right nephrectomy (Sham), (4) I-R, and (5) I-R + ginger (I-R+G). To induce renal ischemia, animals were unilaterally nephrectomized and subjected to 45 min of left renal pedicle occlusion with 24 h reperfusion. Ginger was administered orally 24 h and just before ischemia. At the end of the experiment, blood samples and urine were collected. The following renal functional parameters were studied: serum and urinary levels of creatinine and urea, fractional excretion of sodium, and creatinine clearance. Histopathological examination of the kidney was also performed. Rats with renal I-R showed a significant increase in creatinine and urea concentration in serum and also a significant decrease in creatinine clearance compared with the other groups. In addition, renal histopathology in the I-R group showed severe alterations such as tubular dilatation and tubular epithelial necrosis. However, these changes were significantly reduced in the I-R+G group. This study suggests that ginger is a useful agent for the prevention of renal ischemia reperfusion-induced injury.


Dermal absorption of niclosamide in rats and minipigs.
The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.


Advances in Single-Cell Sequencing Technology and Its Applications in Triple-Negative Breast Cancer.
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and is mainly treated with chemotherapy-based combination therapy. In recent years, with the increasing development of global precision medicine, single-cell sequencing (SCS) has become one of the most promising technologies in the field of biotechnology. Moreover, the related application of this technology in TNBC has been applied and developed. By using SCS to study the heterogeneity of TNBC tumor cells, metastasis, drug resistance mechanisms, mutations, and cloning; it can further guide clinical chemotherapy, targeted therapy, and immunotherapy. To further reflect the importance of SCS in TNBC, this paper elaborated on and summarized the research and application progress of SCS in TNBC.