The stress response and anesthetic potency of unilateral spinal anesthesia for total Hip Replacement in geriatric patients.
Recently, some scholars suggested that it is important to keep a stablehemodynamic state and prevent the stress responses in geriatric patients undergoing total hip replacement (THR). We conducted this randomized prospective study to observe anesthetic potency of unilateral spinal anesthesia and stress response to it in geriatric patients during THR. We compared the effect of unilateral spinal and bilateral spinal on inhibition of stress response through measuring Norepinephrine (NE), epinephrine (E) and cortisol (CORT). Plasma concentrations of NE, E and CORT were determined in blood samples using ELISA (enzyme-linked immunosorbent assays) at three time points: To (prior to anesthesia) T1 (at the time point of skin closure), T2 (twenty-four hours after the operation). Sixty patients were randomly divided into two groups: group A (unilateral spinal anesthesia) and group B (conventional bilateral spinal anesthesia). 7.5tymg of hypobaric bupivacaine were injected into subarachnoid cavity at group A and 12mg hypobaric bupivacaine were given at group B. The onset time of sensory and motor block, loss of pinprick sensation, degree of motor block, regression of sensory and motor blocks and hemodynamic changes were also recorded. These data were used to evaluate anesthetic potency of spinal anesthesia. The results of this experiment show that unilateral spinal anesthesia can provide restriction of sensory and motor block, minimize the incidence of hypotension and prevent the stress responses undergoing THR. It is optimal anesthesia procedure for geriatric patients by rapid subarachnoid injection of small doses of bupivacaine.


Social experiences during adolescence affect anxiety-like behavior but not aggressiveness in male mice.
Adolescence has lately been recognized as a key developmental phase during which an individual's behavior can be shaped. In a recent study with male mice varying in the expression of the serotonin transporter, escapable adverse social experiences during adolescence led to decreased anxiety-like behavior and increased exploratory and aggressive behavior compared to throughout beneficial experiences. Since in this study some behavioral tests took place with a delay of one week after the last social experiences have been made, it was not clear whether the observed effects really reflected the consequences of the experienced different social environments. To test this, the present study focused on the direct effects of beneficial and adverse social experiences on aggressiveness and anxiety-like behavior in C57BL/6J mice. In contrast to the previous study, behavioral testing took place immediately after the last social experiences had been made. Interestingly, whereas individuals from an escapable adverse environment showed significantly lower levels of anxiety-like and higher levels of exploratory behavior than animals from a beneficial environment, aggressive behavior was not affected. From this, we conclude that different social experiences during adolescence exert immediate effects on anxiety-like but not aggressive behavior in male mice.


Task demands, task interest, and task performance: implications for human subjects research and practicing what we preach.
Through the continuous investigation of humans in organizations, we have learned much about motivation, attitudes, and performance. For example, Yukl and others have helped increase our understanding of influence tactics and the effect they have on the performance of subordinates, supervisors, and peers. Some tactics (and combinations of tactics) lead to resistance, some lead to compliance, and some lead to commitment. In this study, we raise the question of whether or not we incorporate our knowledge of these research findings into the design, implementation, and interpretation of our own research studies that require the participation of human subjects. In a survey of 134 subjects from a previous social science study, we found that performance varied across the sample, consistent with the concepts of resistance, compliance, and commitment. In addition, the variance in performance could be explained, in part, by task interest and perceived task demands. Implications are discussed.


Inhibitors of Human 5-Lipoxygenase Potently Interfere With Prostaglandin Transport.
5-Lipoxygenase (5-LO) is the key enzyme in the formation of pro-inflammatory leukotrienes (LT) which play an important role in a number of inflammatory diseases. Accordingly, 5-LO inhibitors are frequently used to study the role of 5-LO and LT in models of inflammation and cancer. Interestingly, the therapeutic efficacy of these inhibitors is highly variable. Here we show that the frequently used 5-LO inhibitors AA-861, BWA4C, C06, CJ-13,610 and the FDA approved compound zileuton as well as the pan-LO inhibitor nordihydroguaiaretic acid interfere with prostaglandin E2 (PGE2) release into the supernatants of cytokine-stimulated (TNFα/IL-1β) HeLa cervix carcinoma, A549 lung cancer as well as HCA-7 colon carcinoma cells with similar potencies compared to their LT inhibitory activities (IC50 values ranging from 0.1-9.1 µM). In addition, AA-861, BWA4C, CJ-13,610 and zileuton concentration-dependently inhibited bacterial lipopolysaccharide triggered prostaglandin (PG) release into human whole blood. Western Blot analysis revealed that inhibition of expression of enzymes involved in PG synthesis was not part of the underlying mechanism. Also, liberation of arachidonic acid which is the substrate for PG synthesis as well as PGH2 and PGE2 formation were not impaired by the compounds. However, accumulation of intracellular PGE2 was found in the inhibitor treated HeLa cells suggesting inhibition of PG export as major mechanism. Further, experiments showed that the PG exporter ATP-binding cassette transporter multidrug resistance protein 4 (MRP-4) is targeted by the inhibitors and may be involved in the 5-LO inhibitor-mediated PGE2 inhibition. In conclusion, the pharmacological effects of a number of 5-LO inhibitors are compound-specific and involve the potent inhibition of PGE2 export. Results from experimental models on the role of 5-LO in inflammation and pain using 5-LO inhibitors may be misleading and their use as pharmacological tools in experimental models has to be revisited. In addition, 5-LO inhibitors may serve as new scaffolds for the development of potent prostaglandin export inhibitors.


Physical activity, sedentary behavior and pancreatitis risk: Mendelian randomization study.
Although observational studies have shown that physical activity is a protective factor for acute pancreatitis, the causal associations between PA/ sedentary behavior and acute pancreatitis (AP) and chronic pancreatitis (CP) remain unclear. We used Mendelian randomization as a strategy to assess the causalities between exposures and outcomes by simulating randomized experiments with genetic variation. The collected genetic variants data of physical activity were from UK Biobank, the data on sedentary behavior were also from UK Biobank, and both of them could be found in the GWAS catalog, and the data on AP and CP were from FinnGen. There were three physical activity related activity patterns (moderate to vigorous physical activity [MVPA], accelerometer-based physical activity with average acceleration, [AccAve] and accelerometer-based physical activity with accelerations >425 milli-gravities, [Acc425]) and three sedentary behavior-related lifestyle patterns (Leisure screen time [LST], Sedentary commuting, Sedentary behavior at work). We used inverse variance weighted (IVW), weighted median and MR-Egger for the analysis of Mendelian randomization, followed by sensitivity tests with the Cochran Q test, MR-Egger intercepts analysis and MR-PRESSO. A causal relationship was found between LST and acute pancreatitis based on IVW analysis (odds ratios [OR] = 1.38, corresponding 95% confidence intervals [CI] = 1.16-1.64, p = 0.0002) and there were no causal relationships between physical activity/sedentary behavior and chronic pancreatitis. Sensitivity analysis showed no pleiotropy and heterogeneity of the results. Results show that reducing LST contributes to the prevention of acute pancreatitis, thereby reducing the health burden associated with it.


Ballistic Exercise Versus Heavy Resistance Exercise Protocols: Which Resistance Priming Is More Effective for Improving Neuromuscular Performance on the Following Day?
Nishioka, T and Okada, J. Ballistic exercise versus heavy resistance exercise protocols: which resistance priming is more effective for improving neuromuscular performance on the following day? J Strength Cond Res 37(10): 1939-1946, 2023-This study aimed to determine whether ballistic exercise priming (BEP) or heavy resistance priming (HRP) is more effective for improving ballistic performance after 24 hours. Ten resistance-trained men performed BEP and HRP conditions 72-144 hours apart in a randomized and counterbalanced order. Jumping performance was assessed before and 24 hours after the BEP and HRP sessions using 0 and 40% one-repetition maximum (1RM) squat jump (SJ), 0 and 40% 1RM countermovement jump (CMJ), and drop jump (DJ) reactive strength index (RSI). Statistical significance was accepted at p ≤ 0.05. In the BEP condition, 0% 1RM CMJ height (+3.62%) as well as theoretical maximum velocity (+5.14%) and theoretical maximum power (+2.55%) obtained from CMJ 24 hours after the priming session were significantly greater than those at the baseline ( p ≤ 0.05), but 0% 1RM SJ height and DJ RSI ( p > 0.05) were not greater than those at the baseline. In the HRP condition, the jump performances were not improved ( p > 0.05). The percentage change in 0% 1RM CMJ height in the BEP condition was significantly greater than that seen in the HRP condition ( p = 0.015) but did not differ for 0% 1RM SJ height and DJ RSI ( p > 0.05). These results suggest that the BEP is more effective than HRP in improving CMJ performance after 24 hours. Therefore, practitioners should consider prescribing resistance priming using low-load ballistic exercises rather than high-load traditional exercises when planning to enhance athlete performance on the following day.


Electron partitioning between the two branching quinol-oxidizing pathways in Acanthamoeba castellanii mitochondria during steady-state state 3 respiration.
Amoeba mitochondria possess a respiratory chain with two quinol-oxidizing pathways: the cytochrome pathway and the cyanide-resistant alternative oxidase pathway. The ADP/O method, based on the non-phosphorylating property of alternative oxidase, was used to determine contributions of both pathways in overall state 3 respiration in the presence of GMP (an activator of the alternative oxidase in amoeba) and succinate as oxidizable substrate. This method involves pair measurements of ADP/O ratios plus and minus benzohydroxamate (an inhibitor of the alternative oxidase). The requirements of the method are listed and verified. When overall state 3 respiration was decreased by increasing concentrations of n-butyl malonate (a non-penetrating inhibitor of succinate uptake), the quinone reduction level declined. At the same time, the alternative pathway contribution decreased sharply and became negligible when quinone redox state was lower than 50%, whereas the cytochrome pathway contribution first increased and then passed through a maximum at a quinone redox state of 58% and sharply decreased at a lower level of quinone reduction. This study is the first attempt to examine the steady-state kinetics of the two quinol-oxidizing pathways when both are active and to describe electron partitioning between them when the steady-state rate of the quinone-reducing pathway is varied.


In vitro activity of cefoperazone-sulbactam combination against gram negative bacilli.
Cefoperazone is a â-lactam antimicrobial and Sulbactam is an irreversible â-lactamase inhibitor. The objective of this study was to know the susceptibility pattern of gram negative bacilli (GNB) towards cefoperazone-sulbactum. All GNB isolated from different clinical samples during the period of May, 2010 to Aug, 2010 were tested for susceptibility to cefoperazone-sulbactum, meropenem, ceftazidime, cefotaxime, ceftriaxone, chloromphenicol, cotrimoxazole, ampicillin, amikacin, nalidixic acid, ciprofloxacin, carbenicillin and piperacillin using standard Kirby-Bauer disc diffusion antimicrobial susceptibility testing method. The susceptibilities were recorded according to CLSI guidelines. A total of 406 GNB were isolated (urine: 66.7%, pus: 19.2%, and blood: 7.9%). Escherichia coli (54.4%) was most frequently isolated organisms followed by Acinetobacter species (17.7%), Klebsiella pneumoniae (9.1%) and Pseudomonas species (6.1%). Overall, 11.8% of isolates showed resistance to cefoperazone-sulbactam. Frequencies of isolates showing resistance to meropenem and amikacin were 14.7% and 26.25% respectively. Only 3.9% of Escherichia coli isolates showed resistance to cefoperazone-sulbactam. For other organisms, their lowest frequency ranging from 0-20%, exhibited resistance to meropenem. In Pseudomonas spp, in-vitro activity of amikacin was also better as only 11.1% isolates showed resistance to it. This study demonstrated the in-vitro synergistic effect of cefoperazonerazone-sulbactam and meropenem having good activity against GNB compared to the activity of other commonly tested antimicrobials. Cefoperazone-sulbactam can be recommended for the clinical practice against GNB exhibiting resistant to other antimicrobials as it is cheaper alternative to meropenem. Our results also focused on the continuous surveillance of the trends and features of resistance of common antimicrobials.


Endocrinal dysfunction in children with Down syndrome.
Down syndrome (DS) is the most common genetic disorder in live-born infants. Children with DS are at increased risk of numerous endocrinal comorbidities. The information contained in this article will provide pediatricians with a narrative overview of different presentations, diagnoses, and management recommendations of various endocrinal disorders in children with DS. We systematically searched PubMed, Embase, Google Scholar, MEDLINE, EBSCO, and Science Direct, and potentially relevant articles were identified and retrieved from electronic and print journals.


Self-transmissible plasmid in Zymomonas mobilis carrying antibiotic resistance.
The cryptic plasmid pRUT41 from Zymomonas mobilis was examined for its biological properties. This plasmid was found to be conjugally transferred from Z. mobilis CP4 to Escherichia coli BM21 and to carry genes for antibiotic resistance (gentamicin, kanamycin, and streptomycin). Covalently closed circular plasmid DNA was isolated from eight transconjugants of E. coli BM21. These plasmids were identical in mobility on agarose gels and exhibited the same restriction patterns as the native pRUT41 plasmid isolated from Z. mobilis. The plasmid location of the antibiotic resistance genes was further confirmed by transforming E. coli BM21 with isolated pRUT41 plasmid from strain CP4 and with plasmids from the transconjugants of BM21. Resistance to streptomycin, kanamycin, and gentamicin was tightly linked and transferred together in all cases.


[Langerhans cell histiocytosis of the thyroid].
Langerhans histiocytosis is a disease with a very diverse clinical spectrum and a very varied prognosis. The thyroid localization is relatively rare, and raises diagnostic and therapeutic difficulties. Diagnosis often requires recourse to clinical, radiological and pathological confrontation. Combined medical and surgical treatment is indicated and requires close multidisciplinary cooperation. On the basis of a new observation and data in the literature, we present a progress report on the clinical and therapeutic options preferred by various authors.


Hedonic-specific activity in piriform cortex during odor imagery mimics that during odor perception.
Although it is known that visual imagery is accompanied by activity in visual cortical areas, including primary visual cortex, whether olfactory imagery exists remains controversial. Here we asked whether cue-dependent olfactory imagery was similarly accompanied by activity in olfactory cortex, and in particular whether hedonic-specific patterns of activity evident in olfactory perception would also be present during olfactory imagery. We used functional magnetic resonance imaging to measure activity in subjects who alternated between smelling and imagining pleasant and unpleasant odors. Activity induced by imagining odors mimicked that induced by perceiving real odorants, not only in the particular brain regions activated, but also in its hedonic-specific pattern. For both real and imagined odors, unpleasant stimuli induced greater activity than pleasant stimuli in the left frontal portion of piriform cortex and left insula. These findings combine with findings from other modalities to suggest activation of primary sensory cortical structures during mental imagery of sensory events.


The ICD-11 classification of personality disorders: a European perspective on challenges and opportunities.
The 11th revision of the World Health Organization (WHO) International Classification of Diseases (ICD-11) includes a fundamentally new approach to Personality Disorders (PD). ICD-11 is expected to be implemented first in European countries before other WHO member states. The present paper provides an overview of this new ICD-11 model including PD severity classification, trait domain specifiers, and the additional borderline pattern specifier. We discuss the perceived challenges and opportunities of using the ICD-11 approach with particular focus on its continuity and discontinuity with familiar PD categories such as avoidant PD and narcissistic PD. The advent of the ICD-11 PD classification involves major changes for health care workers, researchers, administrators, and service providers as well as patients and families involved. The anticipated challenges and opportunities are put forward in terms of specific unanswered questions. It is our hope that these questions will stimulate further research and discussion among researchers and clinicians in the coming years.


The study of (Methyl-3H)decamethonium dichloride incorporation into normal and dystrophic mouse muscle.
1. (Methyl-3H)decamethonium dichloride was injected intravenously into the tail vein of dystrophic and normal mice of the Bar Harbour strain 129 ReJ/dy in paralysing doses. 2. Scintillation counts were made of 1 mm sections of diaphragm and tibialis anterior which showed a normal distribution of tritiated decamethonium in the dystrophic animals. 3. Intraperitoneal injections of L-(gamma-3H)leucine were made into dystrophic and normal mice. Examination of diaphragm and tibialis anterior by scintillation counting showed the abnormal uptake typical of dystrophic involvement of murine muscle. 4. The normal distribution of (methyl-3H)decamethonium dichloride uptake by the dystrophic muscle does not support the concept of active denervation in this disease.


Internal carotid arterial occlusion simulating extracerebral hematoma: relation to diagnosis of stroke.
In 2 elderly male patients, a progressive neurologic deficit and alteration of consciousness developed following substantial head trauma succeeded by an asymptomatic "lucid" interval. The sequence of events and the associated electroencephalographic, echoencephalographic and cerebrospinal fluid findings strongly suggested the presence of an extracerebral hematoma. The cerebral angiographic study, however, disclosed complete occlusion of the extracranial portion of the internal carotid artery in both patients. This report stresses the diagnostic difficulties sometimes encountered in relation to stroke patients.


[Medical image segmentation techniques].
Medical image segmentation is an important application of image segmentation. However it is the bottleneck that restrains medical image application in clinical practice. In this paper, the aim and significance of medical image segmentation are discussed, the development of medical image segmentation techniques is sketched, and a review of the medical image segmentation techniques is given.


Terminal arrhythmia in a patient with Mustard's operation.
In spite of significant improvements in outcome, adults surviving the Mustard procedure continue to be at risk of premature death, cardiac failure, and arrhythmias. Primary ventricular fibrillation as a cause of sudden death in these patients may not be uncommon, and implantation of a defibrillator should be considered, particularly if there is systemic ventricular dysfunction and pre-existing heart block.


Discriminating Gaussian processes via quadratic form statistics.
Gaussian processes are powerful tools for modeling and predicting various numerical data. Hence, checking their quality of fit becomes a vital issue. In this article, we introduce a testing methodology for general Gaussian processes based on a quadratic form statistic. We illustrate the methodology on three statistical tests recently introduced in the literature, which are based on the sample autocovariance function, time average mean-squared displacement, and detrended moving average statistics. We compare the usefulness of the tests by taking into consideration three very important Gaussian processes: the fractional Brownian motion, which is self-similar with stationary increments (SSSIs), scaled Brownian motion, which is self-similar with independent increments (SSIIs), and the Ornstein-Uhlenbeck (OU) process, which is stationary. We show that the considered statistics' ability to distinguish between these Gaussian processes is high, and we identify the best performing tests for different scenarios. We also find that there is no omnibus quadratic form test; however, the detrended moving average test seems to be the first choice in distinguishing between same processes with different parameters. We also show that the detrended moving average method outperforms the Cholesky method. Based on the previous findings, we introduce a novel procedure of discriminating between Gaussian SSSI, SSII, and stationary processes. Finally, we illustrate the proposed procedure by applying it to real-world data, namely, the daily EURUSD currency exchange rates, and show that the data can be modeled by the OU process.


Causes of peripheral cytopenia in hepatitic cirrhosis and portal hypertensive splenomegaly.
The clinical data of 183 patients with hepatitic cirrhosis and portal hypertensive splenomegaly complicated by peripheral cytopenia were retrospectively analyzed to investigate the causes of peripheral cytopenia, as well as the proportion of the causes in these patients. All patients underwent splenectomy. Before operation, these patients had one or more types of peripheral cytopenia (cumulative cytopenia: 390 patient-times). After splenectomy, blood counts in 79.2% (309/390) returned to normal, while in 15.9% (62/390) they increased but failed to reach to normal levels, and in 4.9% (19/390) they became lower than before the operations. For the last group of patients ( n = 19), long-term follow-up showed that blood counts returned to normal in five patients. In other words, in 80.5% [(309 + 5)/390 or 314/390] of patient-times, the peripheral cytopenia was due to hypersplenism, in 15.9% it was due to a combination of factors, and in 3.6% [14/390] it had nothing to do with the hypersplenism. Thus, hypersplenism is a major cause, but not the only cause, of peripheral cytopenia in patients with hepatic cirrhosis and portal hypertensive splenomegaly, and splenectormy is an effective treatment for these patients. Impact statement For a long time, the development of peripheral cytopenias as a complication to cirrhotic portal hypertension has been attributed to hypersplenism; however, this has never been fully demonstrated. Dameshek summarized that hypersplenism should be diagnosed by the presence of four conditions: (a) mono- or multi-lineage peripheral cytopenias; (b) compensatory hyperplasia of bone marrow; (c) splenomegaly; and (d) correction of cytopenias after splenectomy. We retrospectively analyzed the clinical data from 183 surgical patients, and found that 80.5% of peripheral cytopenias was caused by hypersplenism, 16% by a combination of factors, and 3.5% by other factors unrelated to hypersplenism. As the first quantitative findings in this field, our results verify that hypersplenism is a major, but not exclusive, cause of peripheral cytopenias, and provides important clinical evidence for investigating the cause of peripheral cytopenias.


Chronobiology of labour pain perception: an observational study.
Circadian variation may affect many biological and pharmacological phenomena. To assess circadian variations in labour pain perception, 222 consecutive nulliparous women with uncomplicated pregnancy, spontaneous labour, cervical dilatation (3-5 cm), ruptured membranes and normal fetal heart rate tracings were studied. Visual analogue pain scores (VAPS) were analysed and divided into four periods: night (1:01 a.m. to 7:00 a.m.), morning (7:01 a.m. to 1:00 p.m.), afternoon (1:01 p.m. to 7:00 p.m.) and evening (7:01 p.m. to 1:00 a.m.). VAPS were also compared between daytime (morning+afternoon) and nocturnal (evening+night) periods. Daytime mean VAPS were lower than nocturnal scores [75.6 (15.1) vs 85.7 (14.1), P<0.0001]. VAPS were lower in the morning than in the afternoon, evening and night periods (anova, P<0.0001). Labour pain perception appears to be chronobiological, and this might be taken into account when enrolling parturients in studies designed to assess or treat labour pain.


Contractility of the epididymal duct: function, regulation and potential drug effects
During their transit through the epididymis, spermatozoa mature and acquire motility and fertilizing capacity. The smooth muscle cells (SMCs) of the epididymal duct are thought to be responsible for the adequate transport of spermatozoa. Thus, precise regulation of SMC function also represents a prerequisite for sperm maturation thereby contributing to male fertility. In this review, we would like to highlight various aspects of epididymal SMC function and discuss several angles with respect to regulation of contraction and relaxation. Different to the vas deferens, where disturbed SMC pathways resulting in male infertility could be defined, comparable information is missing in the epididymis. We therefore include some vas deferens data which could also be useful for a better understanding of epididymal SMC function. Furthermore, we would like to draw attention to drugs used in clinical practice and their potential (side) effects on contractions in the epididymis.


Follow-up with 18FDG-PET-CT after radical radiotherapy with or without chemotherapy allows the detection of potentially curable progressive disease in non-small cell lung cancer patients: a prospective study.
Follow-up of patients treated with curative intent for non-small cell lung cancer (NSCLC) with X-ray or CT-scans is of unproven value. Furthermore, most patients with progressive disease present with symptoms outside of follow-up visits. Because the accuracy of (18)FDG-PET-CT is superior to CT, we hypothesised that FDG-PET-CT scans 3 months post-treatment could lead to early detection of progressive disease (PD) amenable for radical treatment. Hundred patients with NSCLC, treated with curative intent with (chemo) radiation, were prospectively evaluated. All patients underwent a planned FDG-PET-CT scan 3 months after the start of radiotherapy. Twenty four patients had PD 3 months post-treatment. 16/24 patients were symptomatic. No curative treatment could be offered to any of these patients. In 3/8 asymptomatic patients progression, potentially amenable for radical therapy was found, which were all detected with PET, not with CT only. PET-scanning after curative treatment for NSCLC led to the detection of progression potentially amenable for radical treatment in a small proportion (3%) of patients. Selectively offering a PET-CT scan to the patient group without symptoms could possibly lead to an effective follow-up method.


Plasma Small Extracellular Vesicle Cardiac miRNA Expression in Patients with Ischemic Heart Failure, Randomized to Percutaneous Intramyocardial Treatment of Adipose Derived Stem Cells or Placebo: Subanalysis of the SCIENCE Study.
Small extracellular vesicles (EVs) and their cargo are an important component of cell-to-cell communication in cardiac disease. Allogeneic adipose derived stem cells (ADSCs) are thought to be a potential approach for cardiac regenerative therapy in ischemic heart disease. The SCIENCE study investigated the effect of ADSCs administered via intramyocardial injection on cardiac function in patients with ischemic heart disease. The aim of this substudy, based on samples from 15 patients, was to explore small EV miRNA dynamics after treatment with ADSCs compared to a placebo. Small EVs were isolated at several timepoints after the percutaneous intramyocardial application of ADSCs. No significant effect of ADSC treatment on small EV concentration was detected. After 12 months, the expression of miR-126 decreased significantly in ADSC patients, but not in the placebo-treated group. However, all cardiac miRNAs correlated with plasma cardiac biomarkers. In line with the overall negative results of the SCIENCE study, with the exception of one miR, we did not detect any significant regulation of small EV miRNAs in this patient collective.


Radical retropubic prostatectomy for localised prostatic carcinoma: a clinical and pathological study of 201 cases.
To examine the role of radical retropubic prostatectomy in clinically localised prostatic cancer we reviewed a series of 201 patients all of whom had undergone bilateral pelvic lymphadenectomy. Frozen section showed metastatic pelvic lymph nodes in 13 cases and 6 cases were too locally advanced for operation; prostatectomy was done for the remaining 182. The pathological staging was based on examination of sections of the whole organ. In 109 (60%) the carcinoma was confined to the prostate gland or to the specimen, in 46 (25%) there was carcinomatous growth in the surgical margin, and in 27 (15%) there was invasion of the seminal vesicles. The Gleason score was significantly higher in cases with involvement of the surgical margin or seminal vesicles. There was one operative death (of pulmonary embolism), and the postoperative cardiovascular morbidity was 7%. The incidence of wound infection was 6%, and there were two rectal injuries and three symptomatic lymphoceles. A total of 135/170 evaluable patients (79%) were completely continent postoperatively, and only two developed severe incontinence. Erectile potency was preserved in 24 of 126 (19%). We conclude that radical retropubic prostatectomy is safe and that the complication rate is acceptable. The completeness of the tumour excision seems to be associated with the pathological grade of the tumour.


Plasma antidiuretic hormone levels in patients with normal and low renin essential hypertension, and secondary hypertension.
In order to investigate the antidiuretic hormone (ADH) in essential hypertension and secondary hypertension, plasma ADH levels were measured in normal subjects, in patients with normal and low essential hypertension, and in other patients with various forms of secondary hypertension. Plasma ADH levels were significantly lower in low renin essential hypertension and higher in malignant hypertension than in normal subjects. The plasma ADH levels tended to be lower in renal hypertension and primary aldosteronism, and higher in renovascular hypertension, but these differences were not statistically significant. From these results, it appeared that ADH might play a role in malignant hypertension, but not in the other hypertensive diseases.


Changing chemical composition of precipitation in Wilmington, North Carolina, U.S.A.: implications for the Continental U.S.A.
The H+(aq) concentration in Wilmington, NC, precipitation has decreased by approximately 50% during the preceding two decades, similar to trends seen nationwide. The decrease in acidity is important because solution pH plays a key role in atmospheric reactions, and because the change is so large. This study presents the first long-range study of dissolved organic carbon (DOC) levels in precipitation which demonstrates that DOC concentrations have decreased by approximately half in Wilmington, NC, precipitation. The concentrations of H+(aq) and DOC are highly correlated primarily because small organic acids contribute to both DOC and H+(aq) in precipitation. Ammonium ion concentrations in precipitation have increased due to increased agricultural activities, and this also affects precipitation pH. The reduction of SO2 emissions in 1995 imposed by the Clean Air Act Amendment, better control of emissions of volatile organic compounds, and the increase in ammonia emissions all contribute to the decreasing H+(aq) in precipitation nationwide. These compositional changes in precipitation have many environmental implications, such as decreased acid deposition to lakes, changing speciation for trace metals in precipitation, increased ammonium deposition to coastal waters, and decreased DOC transport to the open ocean.


Reverse Flow: The Role of Built Environments in Shaping Disaster.
In contrast to approaches that examine the impacts of human-built efforts to ameliorate calamitous natural events, this essay argues that a wide array of large structures shape the outcomes of these events. Further, significant human artifacts can succeed in their function vis-à-vis one set of natural events, but can have unanticipated, even reverse effects when natural forces exceed planned expectations. Risk assessments do not normally consider such side effects, suffering from an agnotological narrowing of focus. The historian's emphasis on temporal contextualization and contingency has important implications for policy and assessment of risk.


Substituent effect on lysozyme-catalysed hydrolysis of some beta-aryl di-N-acetylchitobiosides.
Measurements are reported on the kinetics of the lysozyme-catalysed hydrolysis of several beta-aryl di-N-acetylchitobiosides, some of which have been synthesized for the first time. The catalytic rate constants (k(cat.)) at 45 degrees yield a curved Hammett plot (concave up) and the plot of DeltaH(double dagger) versus DeltaS(double dagger) has a sharp break. Substrates with electron-withdrawing groups exhibit a kinetic deuterium isotope effect (k(H) (cat.)/k(D) (cat.)), whereas those with electron-donating groups show no such isotope effect. The results suggest the operation of different mechanisms for the two types of substrates.


Curcumin induces cell death in human uveal melanoma cells through mitochondrial pathway.
To study the cytotoxic effects and related signaling pathways of curcumin on human uveal melanoma cells in vitro. Two human uveal melanoma cell lines (M21 and SP6.5), scleral fibroblasts, and choroidal melanocytes were treated with curcumin. The effects of curcumin on cell viability were assessed by using the MTT (3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide) assay. Cytosol cytochrome c levels and the activities of caspase-9 and caspase-3 were measured by using an enzyme-linked immunosorbent assay. Curcumin induced cell death of cultured human uveal melanoma cells in a dose-dependent manner (10, 30, and 100 microM) and time-dependent manner (3-48 hr), with IC50 at 19.05 microM and 22.39 microM in M21 and SP6.5 cell lines, respectively. Curcumin at lower concentrations (10-30 microM) selectively reduced the cell viability of uveal melanoma cells, without affecting cell viability of fibroblasts and choroidal melanocytes. Curcumin significantly increased the level of cytosol cytochrome c (2-fold greater than the controls after 2 hr treatment), caspase-9 and caspase-3 activities (approximately 4.5- and 6-fold greater than the controls after 2-6 hr treatment, respectively) in a dose-dependent manner. Curcumin has selectively potent cytotoxic effects on cultured human uveal melanoma cells. This effect is associated with the release of cytochrome c from the mitochondria and the activation of caspase-9 and caspase-3 in uveal melanoma cells after treatment with curcumin.


A Novel and Sensitive Approach for the Evaluation of Liver Ischemia-Reperfusion Injury After Liver Transplantation.
The purpose of our study was to evaluate the potential of x-ray propagation-based phase-contrast imaging (PCI) computed tomography (CT) for the detection and characterization of early changes after ischemia-reperfusion (IR) in a standardized rat liver transplantation (LTx) model. Syngeneic orthotopic liver transplantation was performed in male Lewis rats. Ischemia-reperfusion injury (IRI)-induced changes of liver parenchyma were investigated in a time-dependent manner (2, 16, 24, and 32 hours). X-ray phase-contrast images of formalin-fixated liver specimens were acquired in CT mode by using a voxel size of 8 × 8 × 8 μm. Necrapoptotic cell death was visualized with the TdT-mediated dUTP-biotin nick end labeling technique, and alterations of liver graft microhemodynamics, that is, acinar and sinusoidal perfusion failure, were evaluated by in vivo fluorescence microscopy. Acquired and reconstructed PCI-CT images showed an increase in necrotic liver parenchyma dependent on cold storage time, measuring 5.7% ± 1.6% after 2 hours (comparable to 2.6% ± 0.4% for sham livers), 11.5% ± 2.1% (16 hours; P < 0.05 vs control), 23.0% ± 0.5% (24 hours; P < 0.001 vs control), and 31.3% ± 2.2% (32 hours; P < 0.001 vs control). There were a significant lower number of perfused acini in dependence on increasing cold storage time. The acinar perfusion index reached 0.970 ± 0.006 after 2 hours of cold ischemia (comparable to 0.960 ± 0.009 for sham livers) and declined continuously after 16, 24, and 32 hours cold ischemia (0.58 ± 0.03, 0.49 ± 0.02, 0.41 ± 0.03, each P < 0.0001 vs controls). Comparable results were found for sinusoidal perfusion, reaching 1.8% ± 0.4% of nonperfused sinusoids for 2 hours of cold ischemia and 8.2% ± 0.8% after 16 hours, 18.8% ± 1.4% after 24 hours, and 39.0% ± 2.4% after 32 hours (each P < 0.0001 vs controls). Prolonged cold ischemia was associated with an increasing number of TdT-mediated dUTP-biotin nick end labeling-positive cells (hepatocytes and sinusoidal lining cells), reaching 0.4 ± 0.1 (sham), 0.7 ± 0.4 (2 hours), 6.4 ± 1.1 (16 hours), 2.1 ± 0.3 (24 hours), and 14.7 ± 3.5 (32 hours; P = 0.002) for hepatocytes. X-ray PCI of histological liver specimens can detect IR-induced tissue necrosis and can provide detailed complementary 3-dimensional information to standard histopathologic findings.


The Influence of the Distal Resection Margin Length on Local Recurrence and long- term Survival in Patients with Rectal Cancer after Chemoradiotherapy and Sphincter- Preserving Rectal Resection.
Low recurrence rates and long term survival are the main therapeutic goals of rectal cancer surgery. Complete, margin- negative resection confers the greatest chance for a cure. The aim of our study was to determine whether the length of the distal resection margin was associated with local recurrence rate and long- term survival. One hundred and nine patients, who underwent sphincter-preserving resection for locally advanced rectal cancer after preoperative chemoradiotherapy between 2006 and 2010 in two tertiary referral centres were included in the study. Distal resection margin lengths were measured on formalin-fixed, pinned specimens. Characteristics of patients with distal resection margin < 8 mm (Group I, n = 27), 8-20 mm (Group II, n = 31) and > 20 mm (Group III, n = 51) were retrospectively analysed and compared. Median (range) follow-up time in Group I was 89 (51-111), in Group II 83 (57-111) and in Group III 80 (45-116) months (p = 0.326), respectively. Univariate survival analysis showed that distal resection margin length was not statistically significantly associated with overall survival or local recurrence rate (p > 0.05). In a multiple Cox regression analysis, after adjusting for pathologic T and N stage (yT, yN), distal resection margin length was still not statistically significantly associated with overall survival. Our study shows that close distal resection margins can be accepted as oncologically safe for sphincter-preserving rectal resections after preoperative chemoradiotherapy.


The syndrome of rhabdomyolysis: complications and treatment.
Rhabdomyolysis is a syndrome of skeletal muscle cell damage that leads to the release of toxic intracellular material into the systemic circulation. The pathogenesis of rhabdomyolysis is based on an increase in free ionized calcium in the cytoplasm. Its main complications include (a) acute renal failure, which is triggered by renal vasoconstriction and ischemia, (b) myoglobin cast formation in the distal convoluted tubules, and (c) direct renal toxic effect of myoglobin on the epithelial cells of proximal convoluted tubules. Other major complications include electrolyte disorders, such as hyperkalemia, which may cause cardiac arrhythmias, metabolic acidosis, hyperphosphatemia, early hypocalcemia, and late hypercalcemia. Compartmental syndrome and disseminated intravascular coagulopathy may also emerge. The management of myoglobinuric acute renal failure includes aggressive fluid administration to restore the hypovolemia and urine alkalization. The concomitant electrolyte and metabolic disorders should also be treated appropriately; hemodialysis should be considered when life-threatening hyperkalemia and metabolic acidosis exist. In the case of compartmental syndrome, it is important to monitor the intra-compartmental pressure and to perform fasciotomy, if required. When diagnosed early and if the appropriate treatment is initiated promptly, the complications of rhabdomyolysis are preventable and the syndrome has a good prognosis.


[Influence of excitatory amino acids on the outcome of cerebral ischemia].
It would appear from an analysis of the molecular mechanisms which determine the post-ischaemic destruction of brain tissue that they primarily involve the action of excitatory aminoacids, together with the inhibition of protein synthesis and the disorderly production of free radicals. The activities of endogenous excitatory aminoacids (glutamate, aspartate) immediately after ischaemia are similar to those of exogenous excitotoxins (kainic acid, N-methyl-D-aspartate). Brain tissue destruction consecutive to ischaemia or hypoglycaemia is mainly found in cerebral structures which contain a large number of glutamate receptors (hippocampus, locus coeruleus, corpus striatum). These lesions are associated with a significant increase in extracellular concentrations of excitatory aminoacids which are responsible for the massive penetration and accumulation of calcium in the cells (nucleus, Golgi complex, mitochondria), and this encourages the synthesis of non-functional proteins and/or proteolysis (direct cytotoxic action). In animals, these post-ischaemic necrotic lesions are prevented by administration of pharmacological antagonists of these neuromediators at receptor level (e.g. 2-amino-7-phosphonoheptanoic acid). These experimental results suggest that excitatory aminoacids play a determinant role in the genesis of post-ischaemic cell death and that the glutamatergic antagonists currently under development may have a therapeutic activity.


A practical alternative to calculating unmet need for family planning.
The standard approach for measuring unmet need for family planning calculates actual, physiological unmet need and is useful for tracking changes at the population level. We propose to supplement it with an alternate approach that relies on individual perceptions and can improve program design and implementation. The proposed approach categorizes individuals by their perceived need for family planning: real met need (current users of a modern method), perceived met need (current users of a traditional method), real no need, perceived no need (those with a physiological need for family planning who perceive no need), and perceived unmet need (those who realize they have a need but do not use a method). We tested this approach using data from Mali (n=425) and Benin (n=1080). We found that traditional method use was significantly higher in Benin than in Mali, resulting in different perceptions of unmet need in the two countries. In Mali, perceived unmet need was much higher. In Benin, perceived unmet need was low because women believed (incorrectly) that they were protected from pregnancy. Perceived no need - women who believed that they could not become pregnant despite the fact that they were fecund and sexually active - was quite high in both countries. We posit that interventions that address perceptions of unmet need, in addition to physiological risk of pregnancy, will more likely be effective in changing behavior. The suggested approach for calculating unmet need supplements the standard calculations and is helpful for designing programs to better address women's and men's individual needs in diverse contexts.


Cyproheptadine: A Potentially Effective Treatment for Functional Gastrointestinal Disorders in Children.
Functional gastrointestinal disorders (FGIDs) negatively affect children's quality of life and health care costs. It has been proposed that alteration of gut serotonin leads to gastrointestinal dysmotility, visceral hypersensitivity, altered gastrointestinal secretions, and brain-gut dysfunction. Cyproheptadine, a serotonin antagonist, has been shown to be a potentially effective and safe treatment option in children who meet the clinical criteria for FGIDs. Well-designed multicenter trials with long-term follow-up are needed to further investigate its efficacy. [Pediatr Ann. 2017;46(3):e120-e125.].


Dectin-3 Deficiency Promotes Colitis Development due to Impaired Antifungal Innate Immune Responses in the Gut.
Interactions between commensal fungi and gut immune system are critical for establishing colonic homeostasis. Here we found that mice deficient in Dectin-3 (Clec4d-/-), a C-type lectin receptor that senses fungal infection, were more susceptible to dextran sodium sulfate (DSS)-induced colitis compared with wild-type mice. The specific fungal burden of Candida (C.) tropicalis was markedly increased in the gut after DSS treatment in Clec4d-/- mice, and supplementation with C. tropicalis aggravated colitis only in Clec4d-/- mice, but not in wild-type controls. Mechanistically, Dectin-3 deficiency impairs phagocytic and fungicidal abilities of macrophages, and C. tropicalis-induced NF-κB activation and cytokine production. The conditioned media derived from Dectin-3-deficient macrophages were defective in promoting tissue repairing in colonic epithelial cells. Finally, anti-fungal therapy was effective in treating colitis in Clec4d-/- mice. These studies identified the role of Dectin-3 and its functional interaction with commensal fungi in intestinal immune system and regulation of colonic homeostasis.


MR demonstration of complete cerebellar and corpus callosum agenesis.
Complete cerebellar agenesis is a very rare entity, which occurs during the early period of embryogenesis and is usually associated with severe motor dysfunction. We report a case of complete cerebellar agenesis with complete corpus callosum agenesis diagnosed on magnetic resonance imaging (MRI). These anomalies were also associated with rudimentary pons.


Genetic Counselors' Experiences and Interest in Telegenetics and Remote Counseling.
In 2009, the National Society of Genetic Counselors Service (NSGC) Delivery Model Task Force defined genetic counseling service delivery models including telephone (genetic counseling provided remotely by telephone) and telegenetics (counseling provided remotely using videoconferencing). Little is known about the experience of genetic counselors practicing telemedicine in the USA. We sought to evaluate perceived satisfaction, advantages, disadvantages, and barriers to the practice and implementation of telegenetics by practicing genetic counselors. A 21-question online survey was distributed via the NSGC's member directory. Descriptive statistics and a thematic analysis were used to analyze data. A total of 344 surveys were completed of which 235 (68.3%) respondents had delivered genetic counseling via telemedicine and 109 (36.6%) had not. Overall genetic counseling providers who had provided telegenetics were satisfied or very satisfied with their position (91%) and those who were not performing telegenetics were at least slightly interested in a telehealth position (92%).The most common appealing reasons for working in or wanting to work in telemedicine included an innovative approach to healthcare delivery, aspects of remote positions such as the ability to work from home, and flexibility of hours. Unappealing characteristics of telemedicine included the inability to see nonverbals, limited psychosocial counseling, and limited social interaction with colleague that is associated with remote positions. Barriers to implementation of telegenetics were noted by 53% of respondents with the largest barrier being billing and reimbursement. The results of this work suggest that telegenetics service organizations could consider increasing social interactions, attempting to use the preferred method of care (video) to increase ability to see nonverbals, offering flexible work hours, and allowing time to address psychosocial issues as they arise in consultations.


Collinear double-pulse laser-induced breakdown spectroscopy based Cd profiling in the soil.
Cadmium (Cd) can migrate in the soil and is readily absorbed by crops. High Cd accumulated in grains poses a huge threat to human health by inhibiting the function of the kidney system. Thus, it is crucial to reveal the content of soil Cd in vertical-depth series using a fast, real-time, and reliable method. For this purpose, laser-induced breakdown spectroscopy (LIBS) combined with multivariate chemometrics was developed to analyze Cd content in the soil with vertical-depth series. Soil samples spiked with different levels of Cd were prepared, and LIBS spectra were obtained by single-pulse LIBS (SP-LIBS) and collinear double-pulse LIBS (CDP-LIBS) with wavelengths of 532 nm and 1064 nm. With appropriate parameters, CDP-LIBS showed better performance in detecting Cd than SP-LIBS. Partial least squares regression (PLSR), genetic algorithm (GA)-optimized back propagation artificial neural network (BP-ANN), and particle swarm optimization (PSO)-optimized least squares-support vector machine (LS-SVM) were tested for quantitative analysis of the spectra after median absolute deviation (MAD), multiple scattering correction (MSC), wavelet transform (WT), spectral averaging, and normalization. PSO-optimized LS-SVM yielded an ideal result, with a coefficient of determination (R2, 0.999) and root mean square error (RMSE, 0.359 mg/Kg) in the prediction dataset. Finally, CDP-LIBS coupled with PSO-optimized LS-SVM was employed to analyze soil Cd content in vertical-depth series to reveal the migration pattern of Cd. Our results indicated that soil Cd had a significant positive relationship with the inverse of soil depth. However, Cd was mainly concentrated in 0-20 cm and rarely leached below 45 cm in the soil. This study suggests that LIBS and its enhancement techniques provide a reliable method for revealing the content of soil Cd in vertical-depth series.


Experimental studies on artificial blood usage for hemodilution during cardiopulmonary bypass.
Although hemodilution is usually utilized during cardiopulmonary bypass (CPB), hemodilution can cause adverse effects such as hypotension and hypoxia. The purpose of this study was to evaluate a novel perfluoro-octyl bromide (PFOB) emulsion, one of perfluorochemicals (PFCs) emulsions, administered during hemodilution CPB. Fifteen dogs were subjected to CPB for 2 hours under mild hypothermia. Animals were divided into three groups; control group, hemodilution group and PFOB group. During the experiment, hemodynamics, complete blood count and blood chemistry were monitored. In addition, serum complement titer (CH50), bradykinin and histamine concentrations were also measured. Heart rate (HR) was markedly elevated in the hemodilution groups (p<0.05). Mean arterial pressure (MAP) did not change in the three groups. White blood cell (WBC) and platelet (PLT) count did not significantly differ among the three groups. Plasma lactate concentration was markedly elevated only in hemodilution group during late phase of CPB (p<0.05). In the hemodilution group, CH50, bradykinin and histamine, were markedly elevated during the CPB and just after CPB (p<0.05). The present study demonstrated possible benefits of the new PFC emulsion during cardiac surgery by counteracting the adverse effects of hemodilution during CPB.


Genome-wide transcriptional profiling reveals molecular signatures of secondary xylem differentiation in Populus tomentosa.
Wood formation occurs via cell division, primary cell wall and secondary wall formation, and programmed cell death in the vascular cambium. Transcriptional profiling of secondary xylem differentiation is essential for understanding the molecular mechanisms underlying wood formation. Differential gene expression in secondary xylem differentiation of Populus has been previously investigated using cDNA microarray analysis. However, little is known about the molecular mechanisms from a genome-wide perspective. In this study, the Affymetrix poplar genome chips containing 61,413 probes were used to investigate the changes in the transcriptome during secondary xylem differentiation in Chinese white poplar (Populus tomentosa). Two xylem tissues (newly formed and lignified) were sampled for genome-wide transcriptional profiling. In total, 6843 genes (~11%) were identified with differential expression in the two xylem tissues. Many genes involved in cell division, primary wall modification, and cellulose synthesis were preferentially expressed in the newly formed xylem. In contrast, many genes, including 4-coumarate:cinnamate-4-hydroxylase (C4H), 4-coumarate:CoA ligase (4CL), cinnamyl alcohol dehydrogenase (CAD), and caffeoyl CoA 3-O-methyltransferase (CCoAOMT), associated with lignin biosynthesis were more transcribed in the lignified xylem. The two xylem tissues also showed differential expression of genes related to various hormones; thus, the secondary xylem differentiation could be regulated by hormone signaling. Furthermore, many transcription factor genes were preferentially expressed in the lignified xylem, suggesting that wood lignification involves extensive transcription regulation. The genome-wide transcriptional profiling of secondary xylem differentiation could provide additional insights into the molecular basis of wood formation in poplar species.


MACULAR ATROPHY AND MACULAR MORPHOLOGY IN AFLIBERCEPT-TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.
To investigate the incidence and predictors of macular atrophy during treatment with aflibercept for neovascular age-related macular degeneration in Japanese patients. This study included patients with treatment-naive subfoveal neovascular age-related macular degeneration treated from December 2012 through January 2015. Patients were treated with bi-monthly aflibercept injections after 3 monthly loading injections for the first year. Diagnosis of retinal pigment epithelial atrophy was made based on color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence. Baseline characteristics and morphological features were analyzed for their association with the development of macular atrophy. This study included 123 eyes that had no baseline macular atrophy and treated with aflibercept injections for 12 months. Thirteen eyes (10.6%) developed new macular atrophy at 12 months. Logistic regression analysis showed that the presence of intraretinal fluid and thinner subfoveal choroidal thickness at baseline were associated with the development of macular atrophy after aflibercept treatment. Macular atrophy developed in about 10% of eyes with neovascular age-related macular degeneration during 12 months of treatment with a fixed regimen of aflibercept. Intraretinal fluid and subfoveal choroidal thickness seem to be predictors for development of macular atrophy after anti-vascular endothelial growth factor (VEGF) therapy.


Molecular profiling of Spitz nevi identified by digital RNA counting.
The molecular properties of benign melanocytic lesions are poorly understood. Only a few studies have been carried out on specific nevi subtypes, including common nevocellular nevi (NCN) or Spitz nevi (SN). Genomic alterations in melanoma-associated oncogenes are typically absent in SN. In the present study, mRNA expressions of 25 SN and 15 NCN were analyzed. Molecular profiling was performed using the RNA NanoString nCounter Gene Expression Platform (number of genes=770). Marker discovery was performed with a training set consisting of seven SN and seven NCN samples from the same patients, and validation was performed using a second set consisting of 18 SN and eight NCN samples. Using the training set, 197 differentially expressed genes were identified in SN versus NCN. Of these, 74 genes were validated in the validation set (false discovery rate q≤0.13). In addition, using random forest and least absolute shrinkage and selection operator feature selection, a molecular signature of SN versus NCN was identified including 15 top-ranked genes. The present study identified a distinct molecular expression profile in SN compared with NCN, even when lesions were obtained from the same patients. Gene set analysis showed upregulation of gene pathways with increased expression of transcripts related to immunomodulatory, inflammatory, and extracellular matrix interactions as well as angiogenesis-associated processes in SN. These findings strongly indicate that SN represent a distinct group of melanocytic neoplasms and evolve differentially and not sequentially from NCN.


Protein characterisation of Brosimum gaudichaudii Trécul latex and study of nanostructured latex film formation.
Brosimum gaudichaudii Tréc. (Moraceae) is a common Brazilian Cerrado plant known by its pharmaceutical industry relevance. The authors investigated the latex protein components and potential biotechnological applications. Some protein fragments had their sequences elucidated, presenting similarities to jacalin and Kunitz-type trypsin inhibitors. Amino acid residue modifications were found, such as glutamine N-terminal residue cyclisation into pyroglutamic acid residue, and mass differences corresponding to hexoses and N-acetylhexosamine presence. The latex was used to produce a nanoscale structured film, which presented an increased attraction and reduced adhesion behaviours. The film presented high homogeneity, as observed by low nanoroughness values, probably because of its intrinsic components, such as the jacalin-like protein that has known agglutination properties. The immobilised Kunitz-type trypsin inhibitor presence in the latex film allow us to point out to applications related to this inhibition, as in active food packaging, since these peptidase inhibitors are able to inhibit pests and microorganism proliferation.


Functional integration of natural killer cells in a microfluidically perfused liver on-a-chip model.
The liver acts as an innate immunity-dominant organ and natural killer (NK) cells, are the main lymphocyte population in the human liver. NK cells are in close interaction with other immune cells, acting as the first line of defense against pathogens, infections, and injury. A previously developed, three-dimensional, perfused liver-on-a-chip comprised of human cells was used to integrate NK cells, representing pivotal immune cells during liver injury and regeneration. The objective of this study was to integrate functional NK cells in an in vitro model of the human liver and assess utilization of the model for NK cell-dependent studies of liver inflammation. NK cells from human blood and liver specimen were isolated by Percoll separation with subsequent magnetic cell separation (MACS), yielding highly purified blood and liver derived NK cells. After stimulation with toll-like-receptor (TLR) agonists (lipopolysaccharides, Pam3CSK4), isolated NK cells showed increased interferon (IFN)-gamma secretion. To study the role of NK cells in a complex hepatic environment, these cells were integrated in the vascular compartment of a microfluidically supported liver-on-a-chip model in close interaction with endothelial and resident macrophages. Successful, functional integration of NK cells was verified by immunofluorescence staining (NKp46), flow cytometry analysis and TLR agonist-dependent secretion of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. Lastly, we observed that inflammatory activation of NK cells in the liver-on-a-chip led to a loss of vascular barrier integrity. Overall, our data shows the first successful, functional integration of NK cells in a liver-on-a-chip model that can be utilized to investigate NK cell-dependent effects on liver inflammation in vitro.


Lessons Learned From COVID-19 Lockdown: An ASPED/MENA Study on Lifestyle Changes and Quality of Life During Ramadan Fasting in Children and Adolescents Living With Type 1 Diabetes.
Lockdown was a unique experience that affected many aspects of life, particularly during the challenge of Ramadan fasting (RF). Studying this can increase understanding of the effects of lifestyle changes on quality of life (QoL) for children with type 1 diabetes (T1D) during RF. A cross-sectional study that assessed the effect of lockdown on lifestyle and QoL on fasting children living with T1D during Ramadan in the Middle East and North Africa region (2020-2021). We compared the child (self) and parent (proxy) reports using PEDQoL v3.0 disease specific questionnaire during lockdown and non-lockdown periods, and assessed correlations with lifestyle changes using regression and gap analyses. A total of 998 reports from 499 children with T1D aged 8 to 18 years (study = 276, control = 223), and their parents during RF in lockdown and non-lockdown periods. Fathers were more involved in their children's care during lockdown (P = .019). Patients had better compliance with treatment (P = .002), a reversed sleep pattern (P = .033), increased food intake (P ⩽ .001), and less exercise (P < .001). Children and parents perceived better QoL during lockdown (P ⩽.001) with no differences between their reports in "Diabetes Symptoms", "Treatment Adherence," and "Communication" domains. Self and proxy reports were different in all domains during non-lockdown (P = <.001-.009). In gap analysis, although not statistically significant, the gap was approximated between children's and parents' perceptions in all domains during lockdown. COVID-19 lockdown had a positive impact on QoL of children living with T1D during RF, possibly due to lifestyle changes and superior psychosocial family dynamics.


The identification of a new Giardia duodenalis assemblage in marine vertebrates and a preliminary analysis of G. duodenalis population biology in marine systems.
Giardia duodenalis is an intestinal parasite of many vertebrates. The presence of G. duodenalis in the marine environment due to anthropogenic and wildlife activity is well documented, including the contributions from untreated sewage and storm water, agricultural run-off and droppings from terrestrial animals. Recently, studies have detected this protistan parasite in the faeces of marine vertebrates such as whales, dolphins, seals and shore birds. To explore the population biology of G. duodenalis in marine life, we determined the prevalence of G. duodenalis in two species of seal (Halichoerus grypus, Phoca vitulina vitulina and Phoca vitulina richardsi) from the east and west coasts of the USA, sequenced two loci from G. duodenalis-positive samples to assess molecular diversity and examined G. duodenalis distribution amongst these seals and other marine vertebrates along the east coast. We found a significant difference in the presence of G. duodenalis between east and west coast seal species. Only the zoonotic lineages of G. duodenalis, Assemblages A and B and a novel lineage, which we designated as Assemblage H, were identified in marine vertebrates. Assemblages A and B are broadly distributed geographically and show a lack of host specificity. Only grey seal (Halichoerus grypus) samples and one gull sample (Larus argentatus) from a northern location of Cape Cod, Massachusetts, USA, showed the presence of Assemblage H haplotypes; only one other study of harbour seals from the Puget Sound region of Washington, USA previously recorded the presence of an Assemblage H haplotype. Assemblage H sequences form a monophyletic clade that appears as divergent from the other seven Assemblages of G. duodenalis as these assemblages are from each other. The discovery of a previously uncharacterised lineage of G. duodenalis suggests that this parasite has more genetic diversity and perhaps a larger host range than previously believed.


Human Immunoglobulin G Cannot Inhibit Fibrinogen Binding by the Genetically Diverse A Domain of Staphylococcus aureus Fibronectin-Binding Protein A.
The fibronectin-binding protein A (FnBPA) is a cell surface-associated protein of Staphylococcus aureus which mediates adherence to the host extracellular matrix and is important for bacterial virulence. Previously, substantial sequence diversity was found among strains in the fibrinogen-binding A domain of this protein, and 7 different isotypes were described. The effect of this sequence diversity on the human antibody response, in terms of both antibody production and antibody function, remains unclear. In this study, we identify five different FnBPA A domain isotypes based on the sequence results of 22 clinical S. aureus isolates, obtained from the same number of patients suffering from bacteremia. Using a bead-based Luminex technique, we measure the patients' total immunoglobulin G (IgG) against the 7 FnBPA isotypes at the onset and during the time course of bacteremia (median of 10 serum samples per patient over a median of 35 days). A significant increase in IgG against the FnBPA A domain, including the isotype carried by the infecting strain, is observed in only three out of 22 patients (14%) after the onset of bacteremia. Using a Luminex-based FnBPA-fibrinogen-binding assay, we find that preincubation of recombinant FnBPA isotypes with IgG from diverse patients does not interfere with binding to fibrinogen. This observation is confirmed using an alternative Luminex-based assay and enzyme-linked immunosorbent assay (ELISA). IMPORTANCE Despite the many in vitro and murine in vivo studies involving FnBPA, the actual presence of this virulence factor during human infection is less well established. Furthermore, it is currently unknown to what extent sequence variation in such a virulence factor affects the human antibody response and the ability of antibodies to interfere with FnBPA function. This study sheds new light on these issues. First, the uniform presence of a patient's IgG against FnBPA indicates the presence and importance of this virulence factor during S. aureus pathogenesis. Second, the absence of an increase in antibody production in most patients following bacteremia indicates the complexity of S. aureus-host interactions, possibly involving immune evasion or lack of expression of FnBPA during invasive infection. Finally, we provide new insights into the inability of human antibodies to interfere with FnBPA-fibrinogen binding. These observations should be taken into account during the development of novel vaccination approaches.


Isolation and identification of the antimicrobial substance included in tempeh using Rhizopus stolonifer NBRC 30816 for fermentation.
In this study, we focus on the antimicrobial properties of tempeh, a soybean fermented food, against oral bacteria. Tempeh showed antimicrobial activity against dental caries pathogenic bacterium Streptococcus mutans at a final concentration of 1 mg/mL. An antimicrobial substance contained in tempeh was present in the 100 kDa or greater fraction generated by ultrafiltration, but it was found not to be proteinaceous by native-PAGE, SDS-PAGE and protein degradation tests. Next, when the fraction was purified with an ODS column, the 80% and 100% methanol eluates showed antimicrobial activity against S. mutans. The 100% methanol eluate was further subjected to a 2nd column purification, and isolation of the target was confirmed by HPLC. When the isolated material was analyzed by ESI-MS, the m/z was 279.234. Further analysis by Raman spectroscopy revealed a peak similar to linoleic acid. This substance also possessed antimicrobial properties equivalent to linoleic acid.


A Fine-Grained and Privacy-Preserving Query Scheme for Fog Computing-Enhanced Location-Based Service.
Location-based services (LBS), as one of the most popular location-awareness applications, has been further developed to achieve low-latency with the assistance of fog computing. However, privacy issues remain a research challenge in the context of fog computing. Therefore, in this paper, we present a fine-grained and privacy-preserving query scheme for fog computing-enhanced location-based services, hereafter referred to as FGPQ. In particular, mobile users can obtain the fine-grained searching result satisfying not only the given spatial range but also the searching content. Detailed privacy analysis shows that our proposed scheme indeed achieves the privacy preservation for the LBS provider and mobile users. In addition, extensive performance analyses and experiments demonstrate that the FGPQ scheme can significantly reduce computational and communication overheads and ensure the low-latency, which outperforms existing state-of-the art schemes. Hence, our proposed scheme is more suitable for real-time LBS searching.


Chemical transformation of molecular ices containing N2O and C2D2 by low energy electrons: New chemical species of astronomical interest.
We have employed electron stimulated desorption (ESD) and x-ray photoelectron spectroscopy (XPS) to study the chemical species generated from multilayer films of N2O, C2D2, and mixtures thereof (i.e., N2O/C2D2) by the impact of low energy electrons with energies between 30 and 70 eV. Our ESD results for pure films of N2O show the production of numerous fragment cations and anions, and of larger molecular ions, of sufficient kinetic energy to escape into vacuum, which are likely formed by ion-molecule scattering in the film. Ion-molecule scattering is also responsible for the production of cations from C2D2 films that contain as many as six or seven carbon atoms. Many of the same anions and cations desorb from N2O/C2D2 mixtures, as well as new species, which is the result of ion-molecule scattering in the film. Anion desorption signals further indicate the formation of C-N containing species within the irradiated films. XPS spectra of N1s, C1s, and O1s lines reveal the fragmentation of N-O bonds and gradual formation of molecules containing species containing O-C=O, C=O, and C-O functional groups. A comparison between ESD and XPS findings suggests that species observed in the ESD channel are primarily products of reactions taking place at the film-vacuum interface, while those observed in the XPS derive from reactions occurring within the solid.


Antinociceptive, anti-inflammatory, and cytotoxic properties of Origanum vulgare essential oil, rich with β-caryophyllene and β-caryophyllene oxide.
Essential oils are of great interest for their analgesic and anti-inflammatory properties. We aimed to study the content of the essential oil of the Origanum vulgare of the Armenian highlands (OVA) in different periods of vegetation and to investigate its antinociceptive and anti-inflammatory effects in mice (in vivo) and cytotoxic action in cultured cells (in vitro). OVA essential oil was extracted from fresh plant material by hydro-distillation. For OVA essential oil contents determination the gas chromatography-mass spectrometry method was used. Formalin and hot plate tests and analysis of cell viability using the methyl-thiazolyl-tetrazolium (MTT) assay were used. The maximal content of β-caryophyllene and β-caryophyllene oxide in OVA essential oil was revealed in the period of blossoming (8.18% and 13.36%, correspondently). In the formalin test, 4% OVA essential oil solution (3.5 mg/mouse) exerts significant antinociceptive and anti-inflammatory effects (P = 0.003). MTT assay shows approximately 60% cytotoxicity in HeLa and Vero cells for 2.0 μL/mL OVA essential oil in media. The wild oregano herb of Armenian highlands, harvested in the blossoming period, may be considered as a valuable source for developing pain-relieving preparations.


BRCA1: a review of structure and putative functions.
BRCA1 is a complex gene implicated in familial breast and ovarian cancer. Although it is almost certainly a tumour suppressor, it is also essential for the normal growth and development of embryonic cells. BRCA1 is probably involved in DNA damage and repair, in cell cycle regulation, and in differentiation of cells. It remains to be established whether all these functions are subserved by single mechanism or pathway. Since the cloning of BRCA1 in 1994, much has been learned about the function of the gene. However, a great deal more still has to be uncovered. The size of the protein coded by the BRCA1 gene and the variety of transcripts argues for a complexity of function and regulation that will provide intellectual and technical challenges for years to come.


Successful treatment of hypodipsic/adipsic hypernatremia in a cat with lobar holoprosencephaly using oral desmopressin.
A 2-year-old female spayed domestic shorthair cat was presented with a history of collapse, possible hypodipsia/adipsia, severe dehydration and hypernatremia. MRI of the brain revealed a failure of separation of the cerebral hemispheres as characterized by an absence of the rostral part of the corpus callosum, fornix and septum pellucidum and the presence of a single fused lateral ventricle. A diagnosis of hypodipsic/adipsic hypernatremia with lobar holoprosencephaly was made. Dietary management of the cat's condition was attempted by increasing oral water intake, but the cat's hypernatremia and azotemia persisted. Plasma arginine vasopressin (AVP) analysis revealed a low concentration of circulating AVP (2.3 pg/ml), prompting therapy with oral desmopressin in addition to the dietary management. This combined therapy decreased water consumption of the cat from 200 ml/day (85 ml/kg/day) to 100 ml/day (30 ml/kg/day), normalized plasma sodium concentration and resolved the azotemia. To our knowledge, this is the second case report of an MRI diagnosis of lobar holoprosencephaly with hypodipsic/adipsic hypernatremia in a cat and the first case report of the successful management of this condition using oral desmopressin. This case report emphasizes that holoprosencephaly should be suspected in cats presented with hypodipsic/adipsic hypernatremia and highlights the utility of MRI in establishing the diagnosis. Measurements of plasma osmolality and AVP concentration corroborate the pathophysiology and support the use of oral desmopressin in addition to dietary management to resolve the hypernatremia.


Microvascular surgical orchiopexy in the treatment of high-lying undescended testes.
Extensive laboratory experiments in animals have led us to believe that autotransplantation of the testis in the human is feasible. To date, nine of our patients (aged 4-13 years) with undescended intra-abdominal testes have undergone autotransplantation. Using a microvascular surgical technique to anastomose the testicular vessels to the inferior epigastric vessels, it has been possible to place the testis in a scrotal position in every case. No postoperative complications have been noted. Follow-up varied from 9 to 18 months and no atrophy of the testis was observed in this period. Doppler investigations on all of the transplanted testes continue to demonstrate good arterial flow. The aim of surgery on the undescended testis is not only to increase the chances of fertility and to diminish the possibility of malignant transformation but also, more importantly perhaps, to prevent possible abnormal psychosexual development in the child.


Effect of supplemental ascorbic acid in a case of torsion dystonia.
Determinations of various catecholamines and their metabolites have been performed on 24-hr urine collecions obtained from a patient with torsion dystonia and compared to values obtained in a control population. This study was initiated following significant symptomatic worsening by the patient with supplemental ascorbic acid at a dosage of 2 g/day. Compared to base-line values, there resulted no significant alteration in urinary excretion of DOPA, dopamine, norepinephrine, epinephrine, or VMA for either the patient or a group of controls, receiving 1 g/day vitamin C. MHPG is the glycol metabolite of norepinephrine, and is produced both in central and systemic tissues, whereas VMA is not synthesized in brain. The MHPG excretion for the patient increased 150% with supplemental ascorbate, whereas the control individuals demonstrated a mean increase of 19.6%. It is possible that the symptomatic worsening by the patient and the increased excretion of MHPG in response to supplemental ascorbic acid are causally related. Ascorbic acid affects catecholamine biosynthesis at two metabolic loci; it is the necessary cofactor for dopamine-beta-hydroxylase and, by maintaining biopterin in reduced form, facilitates tyrosine hydroxylase holoenzyme activity. Thus, the vitamin may have effected increased central synthesis or turnover of norepinephrine, or both, with resultant clinical worsening.


Dual character concepts and the normative dimension of conceptual representation.
Five experiments provide evidence for a class of 'dual character concepts.' Dual character concepts characterize their members in terms of both (a) a set of concrete features and (b) the abstract values that these features serve to realize. As such, these concepts provide two bases for evaluating category members and two different criteria for category membership. Experiment 1 provides support for the notion that dual character concepts have two bases for evaluation. Experiments 2-4 explore the claim that dual character concepts have two different criteria for category membership. The results show that when an object possesses the appropriate concrete features, but does not fulfill the appropriate abstract value, it is judged to be a category member in one sense but not in another. Finally, Experiment 5 uses the theory developed here to construct artificial dual character concepts and examines whether participants react to these artificial concepts in the same way as naturally occurring dual character concepts. The present studies serve to define the nature of dual character concepts and distinguish them from other types of concepts (e.g., natural kind concepts), which share some, but not all of the properties of dual character concepts. More broadly, these phenomena suggest a normative dimension in everyday conceptual representation.


Molecular abnormalities of the desmosomal protein desmoplakin in human disease.
Desmoplakin is the principal plaque protein of desmosomes, specialized adhesion junctions found in various tissues including skin, heart and meninges. It is an entirely intracellular protein and in keratinocytes desmoplakin binds to other structural components of desmosomes such as cadherins and armadillo proteins, as well as to keratin filaments. Clues to the biological significance of desmoplakin have recently emerged from a number of naturally occurring human desmoplakin gene mutations. Both autosomal dominant and autosomal recessive disorders have been reported. The spectrum of clinical features includes varying degrees of keratoderma, blisters, nail dystrophy, woolly hair and, in some cases, cardiomyopathy. This review provides an update on genotype-phenotype correlation for human desmoplakin mutations as well as an overview of desmoplakin abnormalities in other conditions, including autoimmune blistering diseases, epithelial malignancies and blood vessel morphogenesis.


Anti-nuclear autoantibodies in the general German population: prevalence and lack of association with selected cardiovascular and metabolic disorders-findings of a multicenter population-based study.
We determined the prevalence of anti-nuclear autoantibodies (ANAs) in the German adult population and examined the association between ANAs and cardiovascular and metabolic disorders. We used data and blood samples from the pretest phases of the German National Cohort, obtained from six of the 18 study centers (n = 1199). All centers applied standardized instruments including face-to-face interviews, anthropometric measurements and collection of blood samples. Self-reported histories of diabetes mellitus, heart attack and elevated blood cholesterol and/or lipids were recorded. Height, weight and blood pressure were measured. ANAs were detected using a semi-automated system (AKLIDES®; Medipan GmbH, Dahlewitz, Germany). A positive ANA was defined as a titer ≥ 1:80. ANA were classified as weakly (1:80 or 1:160), moderately (1:320 or 1:640) or strongly (≥1:1280) positive. Specific autoantibodies against nuclear antigens were detected with second-step assays according to the ANA staining pattern. Associations between the assessed disorders and ANA positivity and pattern were examined using sex and age-adjusted mixed-effects logistic regression models. Thirty-three percent (95% confidence interval; 31-36%) of the 1196 participants (measurements could not be obtained from three samples) were ANA positive (titer ≥ 1:80). The proportions of weakly, moderately and strongly positive ANA were 29%, 3.3% and 1.3%, respectively. ANA positivity was more common among women than men across all titers (χ2, p = 0.03). ANA positivity, even when stratified according to height of titer or immunofluorescent pattern, was not associated with diabetes, elevated blood cholesterol and/or lipids, obesity or hypertension. Second-step autoantibody assays were positive in 41 of the 83 samples (49%) tested, with anti-DFS70 (n = 13) and anti-dsDNA (n = 7) being most frequent. These subgroups were too small to test for associations with the disorders assessed. The prevalence of ANA positivity in the German general population was similar to values reported from other countries. Contrary to other studies, there was no association with selected self-reported and objectively measured cardiovascular and metabolic variables.


[Anti-IL17 induced eczema and the yin-yang of Th2 and Th17].
Biologics targeting specific cytokines and pathways have revolutionized the management of patients with chronic inflammatory diseases. However, these treatments have their limitations and, surprisingly, can induce novel inflammatory diseases. Here, we present a case of a psoriasis patient developing anti-IL17 induced eczema, an intriguing side effect of IL-17 blockade. The coexistence of psoriasis and eczema in a single patient is uncommon given their distinct and opposing immune mechanisms. Psoriasis is mainly driven by Th17 cells, whereas atopic dermatitis is Th2-dominated. In this article, we propose the yin yang of Th2 and Th17 with IL-4 and IL17 as principal antipodal vectors that control each other. Thus, blocking one of these cytokines can tip the balance between Th2 and Th17 and lead to the induction of the opposing inflammatory pathway via lifting the controlling mediator.


Assessment of Pre-operative Vaginal Preparation for Laparoscopic Hysterectomy.
Determine the difference in microbial growth from the vagina and uterine manipulator among patients undergoing laparoscopic hysterectomy after randomization to one of three vaginal preparation solutions (10% Povidone-iodine, 2% Chlorhexidine, or 4% Chlorhexidine). This was a prospective randomized controlled trial in an academic community hospital. Patients were ≥ 18 years old and scheduled for laparoscopic hysterectomy for benign and malignant indications. Fifty patients were identified and randomized into each arm. Prior to surgery, the surgical team prepared the vaginal field using 10% Povidone-iodine, 2% Chlorhexidine, or 4% Chlorhexidine, according to group assignment. Cultures were collected from the vagina after initial preparation, prior to the colpotomy, and on surfaces of the uterine manipulator. Bacterial count from the baseline vaginal fornix/cervical canal cultures did not differ significantly among the three groups. There was a difference in bacterial count among the second cervical canal/vaginal fornix cultures (p < 0.01), with the Povidone-iodine arm demonstrating the highest level of growth of cultures (93.8%), followed by 2% Chlorhexidine (47.4%), and 4% Chlorhexidine (20%). There was no difference in growth on the uterine manipulator handle and no difference in vaginal itching or burning was found across the three arms postoperatively. Bacterial growth prior to colpotomy was the lowest with 4% Chlorhexidine followed by 2% Chlorhexidine, the Povidone-iodine group exhibited the highest bacterial growth. There was no difference in moderate to severe vaginal itching or burning. This showed that 4% Chlorhexidine is superior in reducing bacterial growth when used in laparoscopic hysterectomy.


Morbidity experienced by women before and after operative vaginal delivery: prospective cohort study nested within a two-centre randomised controlled trial of restrictive versus routine use of episiotomy.
To explore: (1) the antenatal and postnatal morbidity experienced by women in relation to operative vaginal delivery (OVD); and (2) the impact of restrictive versus routine use of episiotomy. Longitudinal prospective cohort study embedded within a two-centre randomised controlled trial (RCT). Two UK tertiary-level maternity units. Antenatally recruited participants of an RCT of restrictive versus routine use of episiotomy at OVD. A self-completing questionnaire was administered antenatally, before hospital discharge, at 6 weeks and at 1 year postpartum. Urinary and anal incontinence, dyspareunia, perineal pain and psychological morbidity. Longitudinal data have revealed that morbidities historically associated with OVD were often as prevalent, if not more prevalent, in the third trimester of pregnancy than postpartum. Restrictive episiotomy use was associated with: a higher incidence of perineal pain in the immediate postpartum period (98.9% restrictive versus 87.8% routine, RR 1.10, 95% CI 1.01-1.21); greater psychological morbidity in the immediate postpartum period (mean scores on the Edinburgh Postnatal Depression Scale, Edinburgh Postnatal Depression Score (EPDS) 6.7 restrictive versus 5.1 routine; P = 0.01 ); and more stress urinary incontinence at 6 weeks postpartum (42.2% restrictive versus 27.2% routine, RR 1.55, 95% CI 1.00-2.40); however, this had resolved by 1 year. No other differences were found between the groups at 6 weeks and 1 year postpartum. Morbidities previously attributed to OVD may in fact be present antenatally, to a greater or similar degree. A restrictive approach to the use of episiotomy at OVD may increase rates of urinary morbidity, in particular stress incontinence and perineal pain, in the immediate postpartum period.


Cervical dissecting extravasation of oxaliplatin: A case report.
Oxaliplatin is a chemotherapy drug considered to be an irritant and vesicant. Peripheral extravasation could happen following oxaliplatin chemotherapy administration, but mediastinal or cervical events are rare. The present study focused on the case of a 64-year-old female patient with KRAS-mutated colorectal adenocarcinoma. The patient was prescribed folinic acid, fluorouracil and oxaliplatin chemotherapy via a subcutaneous pump or port-a-cath device, which was inserted into the right subclavian vein. The patient reported a sudden throbbing pain in the chest wall and anterior cervical region. After performing a computed tomography scan, anterior cervical collection and jugular-subclavian venous confluence at the distal end was observed at the venous access site of the subcutaneous port-a-cath device, which extended cranially, dissected cervical planes and forming a hydro-aerial collection in the submaxillary region. Subsequently, the port-a-cath device was removed and a warm dry compress was applied. After 2 weeks, the patient had fully recovered without any sequelae at the cervical level. To the best of the authors' knowledge, this is the first case of cervical extravasation of oxaliplatin reported in the literature to date and will help to manage similar situations.


Strongyle egg reappearance period after moxidectin treatment and its relationship with management factors in UK equine populations.
Parasitic nematodes, particularly cyathostomins, are ubiquitous in grazing horses world-wide. Considerable burdens of cyathostomin larvae can encyst in the large intestinal wall. The most recommended treatment against these pathogenic stages is moxidectin. Information is required on how effective moxidectin is against cyathostomin populations in different regions. The objectives here were to determine the efficacy of moxidectin treatment and estimate the strongyle egg reappearance period (ERP) after treatment in several equine populations, to confirm the type of strongyle nematodes present and to identify other (i.e. management) factors associated with shortened ERP. Eight yards were recruited and moxidectin in combination with praziquantel administered to all horses (n=261). Faecal egg count (FEC) analysis was performed at weeks 0, 2, 6, 10 and 12 after treatment to determine efficacy and ERP. The ERP was estimated using two previously published methods. Morphological identification of cultured third stage larvae from the sample population was compared to a Strongylus vulgaris-specific end-point PCR to examine the presence of S. vulgaris in samples before and after treatment. Strongyle egg shedding patterns were also compared to worm management practices at each site. At 2 weeks post-treatment, moxidectin was highly effective (faecal egg count reduction range, 99.9-100%). The strongyle ERP ranged from 6 weeks to >12 weeks depending on the calculation method applied. Only cyathostomin larvae were detected by morphological identification. The results from the coprocultures and PCR showed that S. vulgaris was absent before and after treatment. Analysis revealed that regular faecal removal from pasture was associated with lower average FEC and lower prevalence of egg shedding.


In situ detection of antigenic glycoproteins in Taenia solium metacestodes.
Taenia solium has a complex life cycle. Its cysticercus can lodge in the brain, causing neurocysticercosis (NCC), and the adult tapeworm's survival in the intestine results in taeniasis. In this study, the in situ detection of previously described glycoprotein antigens used for serological diagnosis of NCC and the detection of other glycoconjugates was explored in cysticerci and the surrounding porcine tissue to understand their potential role in pathogenesis. Immunohistochemistry with an antiserum specific for glycoprotein antigens rich in N-linked carbohydrates and in situ histochemistry with a battery of lectins that have affinity to a variety of glycoconjugates were performed. The glycoconjugates rich in N-linked carbohydrates were detected in the vesicular fluid and tegument of the vesicular membrane and scolex, where the parasite has direct contact with the host tissues during cysticercosis and taeniasis, respectively. Additionally, as the inflammatory response progressed, the parasite's antigenic glycoproteins were also detected in the cytoplasm of inflammatory cells in the surrounding granuloma. In contrast, the spiral canal tegument, which will be exposed to intestinal enzymes in taeniasis, had N-acetyl-galactosamine-rich mucins. Thus, the differential saccharidic composition in T. solium metacestode structures may be important for the survival of the parasite in different host sites.


Macromolecular synthesis during conjugation in yeast.
Morphological changes and synthesis of DNA, RNA and protein during conjugation of Saccharomyces cerevisiae was studied. It was found that during conjugation distinct cell expansion and increase in the dry mass of the cell takes place. DNA synthesis is inhibited during mating while synthesis of RNA and protein is not affected. Conjugation of temperature sensitive mutant defective in elongation of DNA chain was normal both in permissive and restrictive temperature. Conjugation of mutants defective in the initiation of DNA synthesis or defective in RNA and protein synthesis was inhibited in restrictive temperature. The results obtained with temperature sensitive mutants suggest that RNA and protein synthesis is necessary for mating reaction while DNA synthesis is not required.


Emerging Strategies in Stimuli-Responsive Nanocarriers as the Drug Delivery System for Enhanced Cancer Therapy.
The conventional Drug Delivery System (DDS) has limitations such as leakage of the drug, toxicity to normal cells and loss of drug efficiency, while the stimuli-responsive DDS is non-toxic to cells, avoiding the leakage and degradation of the drug because of its targeted drug delivery to the pathological site. Thus nanomaterial chemistry enables - the development of smart stimuli-responsive DDS over the conventional DDS. Stimuliresponsive DDS ensures spatial or temporal, on-demand drug delivery to the targeted cancer cells. The DDS is engineered by using the organic (synthetic polymers, liposomes, peptides, aptamer, micelles, dendrimers) and inorganic (zinc oxide, gold, magnetic, quantum dots, metal oxides) materials. Principally, these nanocarriers release the drug at the targeted cells in response to external and internal stimuli such as temperature, light, ultrasound and magnetic field, pH value, redox potential (glutathione), and enzyme. The multi-stimuli responsive DDS is more promising than the single stimuli-responsive DDS in cancer therapy, and it extensively increases drug release and accumulation in the targeted cancer cells, resulting in better tumor cell ablation. In this regard, a handful of multi-stimuli responsive DDS is in clinical trials for further approval. A comprehensive review is crucial for addressing the existing knowledge about multi-stimuli responsive DDS, and hence, we summarized the emerging strategies in tailored ligand functionalized stimuli-responsive nanocarriers as the DDS for cancer therapies.


Lidocaine suppresses glioma cell proliferation by inhibiting TRPM7 channels.
Malignant glioma is the most common brain cancer with devastating prognosis. Recurrence of malignant glioma following surgery is very common with few preventive and therapeutic options. Novel targets and therapeutic agents are constantly sought for better outcome. Our previous study established that inhibition of transient receptor potential melastatin 7 (TRPM7) channels resulted in significant decrease of human glioma cell growth and proliferation. As local anesthetic lidocaine has been shown to inhibit TRPM7 currents, we hypothesize that lidocaine may suppress glioma cell proliferation through TRPM7 channel inhibition. TRPM7 currents were recorded in rat C6 glioma cells using the whole cell patch clamp technique. Cell growth and proliferation were assessed under microscopic examination and biochemical assays. Lidocaine inhibits TRPM7-like currents in a dose-dependent and reversible manner. At 1 and 3 mM, it inhibits ~30% and ~50% of TRPM7 currents. At these concentrations, it is effective in inhibiting the proliferation of C6 cells. As expected, the TRPM7 inhibitors gadolinium and 2-Aminoethoxydiphenyl borate have similar effects on TRPM7 currents and proliferation of C6 cells. Similar to its effect on C6 cells, lidocaine inhibits the proliferation of A172 cells, a human glioblastoma cell line. Lidocaine significantly inhibits the proliferation of glioma cells. The effect of lidocaine is mediated, at least in part, by inhibiting TRPM7 channels.


Increased luminal mucin does not disturb glucose or ovalbumin absorption in rats fed insoluble dietary fiber.
We tested whether increased mucin secretion due to ingestion of insoluble dietary fiber (IDF) affects small intestinal nutrient absorption in rats. Polystyrene foam (PSF) with a true expansion ratio of 54.9 was used as a model for IDF with high bulk-forming properties. In Expt. 1, rats were fed a control diet or diet containing 50 g PSF/kg for 1, 3, 5, or 7 d. Small intestinal mucin fractions were isolated, and O-linked oligosaccharide chains were measured. The luminal mucin content reached a maximum within 5 d after PSF ingestion. In Expt. 2, rats were fed a control diet or diet containing 50 g PSF/kg for 7 d, and then all rats were switched to the control diet for 1, 3, or 5 d. The increased capacity for luminal mucin secretion disappeared within 5 d after ceasing PSF ingestion. In Expt. 3, rats were fed a control diet or diet containing 70 g PSF/kg for 7 d. Glucose (1g/kg) was administered orally after 12 h of food deprivation. The blood glucose concentrations did not differ between the groups. In Expt. 4, rats were fed a control diet or diet containing 90 g PSF/kg for 14 d. At d 7, portal cannulae were installed. A mixed solution of glucose (1g/kg) and ovalbumin (OVA, 250 mg/kg) was orally administered after 12 h of food deprivation, and responses of portal glucose and OVA concentrations were monitored for 120 min. Although luminal mucin contents were almost doubled in the 9% PSF group compared with the control group, neither portal glucose nor OVA concentration differed at any time point. The results suggest that the short-term ingestion of IDF significantly increases the luminal mucin content, but that this does not disturb nutrient absorption.