Maxillary bone metastasis, as an early sign of breast cancer; an unusual & rare site of metastasis from the common cancer.
Oral cavity metastases are considered rare and represent approximately 1% of all oral malignancies. Due to their rarity and atypical clinical and radiographic appearance, metastatic lesions are considered a diagnostic challenge. In this article we present a rare, unusual & exceptional case of left maxillary mass which on further evaluation leading to diagnosis of left breast carcinoma with metastasis to isolated left maxillary bone. Sixty five year old postmenopausal woman of low socioeconomic status with good performance status presented with a 3 months history of progressive pain and swelling in the left maxillary region. Fine Needle Aspiration Cytology (FNAC) from the maxillary mass shows invasive ductal carcinoma. On further clinical, radiographic, and histopathological examination findings from the breast lesion confirmed the diagnosis of hormone receptor positive metastatic breast carcinoma. In view of painful metastatic maxillary lesion with breast disease she was managed with a palliative radiotherapy to the maxillary lesion and palliative chemotherapy with Doxorubicin-Cyclophosphamide and bhisphosphonate-Zolendronic acid. Patient responded very well to palliative radiotherapy and chemotherapy, in view of hormone receptor positive breast cancer, now she is on Tab. Anastrazole 1 mg once a day along with monthly Zolendronic acid injection since last 13 months without any symptoms of disease evolution. A high index of clinical thought of metastatic cancer to maxilla is necessary when evaluating patients who complain of maxillary pain and swelling without a history of pain or swelling in the head and neck & non-head and neck region. To the best of our knowledge, this is the first reported case of a metastatic isolated solitary maxillary bone metastasis presenting as an early sign of breast cancer.


Assessment of oxidative stress after out-of-hospital cardiac arrest.
Pathophysiology of cardiac arrest corresponds to a whole body ischemia-reperfusion. This phenomenon is usually associated with an oxidative stress in various settings, but few data are available on cardiac arrest in human. The aim of the present study was to evaluate different oxidative stress markers in out-of-hospital cardiac arrest (OHCA) patients treated with therapeutic hypothermia. We conducted a prospective study assessing oxidative stress markers (thiobarbituric acid reactive species, carbonyls, thiols, glutathione, and glutathione peroxidase) in OHCA patients treated with therapeutic hypothermia. Measurements were performed during the 4 days after admission and compared between good and poor outcome patients according to Cerebral Performance Category. Thirty-four patients were included, 10 good and 24 poor outcomes at 6 months. Thiobarbituric acid reactive species were higher in the poor outcome group on admission and when therapeutic hypothermia was reached. The other markers were not different between groups. No markers seemed modified by the use of therapeutic hypothermia in each group. After OHCA, good outcome patients exhibit lower oxidative stress markers than poor outcome patients. Thiobarbituric acid reactive species appears to be an early prognostic parameter. Oxidative stress markers seem not mitigated by therapeutic hypothermia.


Ability of optical coherence tomography to detect caries beneath commonly used dental sealants.
The onset and progression of early tooth decay is often preventable with dental sealants. However, occasionally decay progresses underneath the sealant. Current technology does not permit monitoring of potential lesion progression or arrest. Dental sealants themselves mask the visual cues that identify early tooth decay, and radiographs are not sufficiently sensitive. Therefore, clinicians can be reluctant to use dental sealant. The objective of this ex vivo study was to evaluate the ability of dentists to detect decay beneath commonly used dental sealants using optical coherence tomography (OCT) imaging. STUDY DESIGNS/MATERIALS/METHODS: Forty extracted teeth were divided into equal groups of carious and non-carious teeth, as determined by visual inspection. After radiographs and OCT imaging, teeth were randomly assigned for sealant placement with one of four commonly purchased dental sealants: Clinpro™, Fuji Triage™, Embrace Wet Bond™, and Delton™.Following sealant placement, teeth were radiographed, imaged with OCT, sectioned, examined histologically, and scored as healthy/not healthy. OCT and radiographic images were scored separately. The gold standard was histopathological diagnosis from the serial sections.Cohen's kappa, sensitivity, negative predictive value, and positive predictive value were computed for all measures. After 90 minutes training, pre-standardized dentists were able to detect tooth decay more accurately using OCT than with visual or radiographic examination. Detection using OCT was somewhat better prior to sealant placement than afterwards. This effect varied in size depending on the type of sealant used. Radiographic diagnosis was also less accurate after sealant placement. Of the four dental sealants, Delton provided excellent positive predictive value and the best post-sealant negative predictive values. In this ex vivo study, dentists were able to detect tooth decay beneath four commonly used dental sealants based on OCT images. Clinical investigations are now underway to determine the usefulness of this approach in vivo.


Prevalence of eosinophilic esophagitis in patients with refractory gastroesophageal reflux disease symptoms: A prospective study.
Eosinophilic esophagitis (EoE) is not routinely considered in the differential diagnosis of refractory gastroesophageal reflux disease (GERD). To prospectively evaluate the prevalence of EoE and describe the clinical features and predictors of EoE in patients with refractory symptoms of GERD. Esophageal biopsies were obtained in patients with symptoms of GERD refractory to 8 weeks of conventional antisecretory therapy. Diagnosis of EoE was defined as at least 20 eosinophils × high power field and clinical unresponsiveness to proton pump inhibitors. Clinical and manometric features were compared. Independent risk factors predicting EoE were identified. Six out of 150 included patients (4%) met the diagnostic criteria for EoE. Patients with EoE were significantly younger, had significantly more dysphagia, atopy, ineffective esophageal peristalsis, esophageal rings and esophageal strictures than patients without EoE. Independent predictors of EoE were: age under 45 years (OR 4.8, 95% CI 2.4-8.6), dysphagia (OR 12.2, 95% CI 4.3-19.4), and atopy (OR 3.4, 95% CI 1.5-7.4). EoE is an uncommon condition (4%) in patients with refractory symptoms of GERD. Age under 45 years, atopy or dysphagia may warrant suspicion of EoE in this subset of patients.


Tail immersion test for the evaluation of a nociceptive reaction in mice. Methodological considerations.
The effect of two commonly used methods to immobilize the animals, viz. tube restrainer and wrapping in a diaper (chux) on the tail flick latency in immersion test, was evaluated in mice using a stimulus temperature of 50 degrees C. The animals were immobilized either in the tube or chux briefly (25-30 sec) during the tail flick measurements. The basal tail flick latency was 2.8 +/- 0.2 in the tube restrained and 5.5 +/- 0.3 sec in chux restrained groups (p less than 0.001). The analgesic effect of morphine (1, 3, 4, 7, and 10 mg/kg) was significantly higher in the chux-restrained animals as indicated by the dose ratio of 2.16 for the 50% analgesic response in the chux versus tube restrained mice. The tail flick latency, 15 min after naloxone injection (1 and 3 mg/kg), expressed as % of predrug latency was significantly reduced in the chux- but not the tube-restrained group. The hyperalgesic effect of naloxone could not be detected in chux-restrained animals, when the water temperature was increased to 55 degrees C. The results demonstrate that the restraining procedure will influence the analgesic effects of test drugs in tail immersion test. Furthermore, the stimulus temperature appears to be an important variant that could influence the results in this test. The present results demonstrate the hyperalgesic effect of naloxone after systemic administration in the tail immersion test and supports the concept that tail flick response is tonically inhibited by endogenous opioid systems.


Safety and tolerability of emerging pharmacological treatments for bipolar disorder.
Over the past few years numerous new agents have been examined for their efficacy in bipolar disorder (BPD). New antiepileptic agents and atypical antipsychotics currently form the bulk of these emerging agents. As the armamentarium for treating BPD increases, it allows for the possibility of choosing drugs on the basis of their tolerability as well as their efficacy, rather than on efficacy alone. Efficacy data for newer antiepileptic drugs (lamotrigine, topiramate, gabapentin, oxcarbazepine) and atypical antipsychotics (olanzapine, clozapine, risperidone, quetiapine, ziprasidone, aripiprazole) are briefly reviewed. The article focuses on relative safety and tolerability of these agents. In general, most of these newer agents have better side effect and tolerability profiles than older agents commonly used to treat BPD (lithium, valproate, carbamazepine); however, these must be weighed against efficacy demonstrated to date in randomized, controlled trials. Cognitive impairment is a concern with topiramate, weight gain and risk of diabetes with some of the atypical antipsychotic agents, and rash with lamotrigine. Side effects of newer emerging agents for the treatment of BPD can be effectively managed and the risks reduced by instituting practical strategies early in management.


Comparison between magnifying endoscopy and histological, culture and urease test findings from the gastric mucosa of the corpus.
The incidence of Helicobacter pylori infection in Japan is high. Unlike the case in Western countries, H. pylori-induced gastritis in Japanese patients has a tendency to spread to the corpus. H. pylori-induced gastritis is characterized by a number of specific endoscopic findings. In a previous study, the endoscopic features and a magnified view of the gastric mucosa of the corpus of H. pylori-negative normal stomach were described. This report describes the specific histological features and magnified views of the H. pylori-negative stomach and compares them with those seen during H. pylori-induced gastritis. The anterior wall or greater curvature of the middle body of the stomachs of 297 patients were observed by magnifying endoscopy (x 80). Forceps biopsy was performed at the following locations: i) the magnified site, for histological examination; ii) the antral mucosa, for culture/urease test, and histology; and iii) greater curvature of the upper body for culture/urease test. 72 patients were diagnosed as having H. pylori-negative normal stomach and 225 as having H. pylori-positive gastritis. The magnified views were classified into four types: i) collecting venules, with true capillaries forming a network, and gastric pits resembling pinholes (type Z-0; n = 80); ii) irregular true capillaries but no collecting venules observed (type Z-1; n = 36); iii) white gastric pits and sulci, with neither collecting venules nor true capillaries being seen (Z-2; n = 110); and iv) dilated pits with surrounding redness (Z-3; n = 71). All cases of H. pylori-negative normal stomach were type Z-0, whereas H. pylori-induced gastritis was present in all cases where the classification was Z-1, Z-2, or Z-3. Type Z-0 differed significantly from types Z-1, Z-2, and Z-3 with regard to the grade of inflammation, activity, and presence of H. pylori. Collecting venules and true capillaries forming a network with gastric pits in the center (type Z-0) were observed in the H. pylori-negative normal mucosa. The magnified views of H. pylori-related gastritis clearly differed from type Z-0.


Pharmacodynamics of intravenous procainamide as used during acute electropharmacologic testing.
No previous studies have determined the pharmaco-dynamics of intravenous procainamide when administered in a dose of 15 mg/kg and at a rate of 50 mg/min, as is common practice during electropharmacologic testing. In this study, 30 patients received procainamide in this fashion; the right ventricular effective refractory period and the QRS duration at a ventricular pacing rate of 120/minute were then determined every minute for 20 minutes. Ten patients received no maintenance infusion of procainamide (group A), 10 received a 4 mg/min maintenance infusion (group B) and 10 received an 8 mg/min maintenance infusion (group C). Ten additional patients received no procainamide and served as control subjects (group D). The plasma procainamide concentration was measured at 1, 5, 10, 15 and 20 minutes after the loading dose was administered. A stable plasma procainamide concentration was not present in group A, B, or C until 15 minutes after infusion of the loading dose. The effective refractory period and QRS duration increased compared with baseline at 1 minute, decreased between 1 and 10 minutes and then remained essentially unchanged between 10 and 20 minutes in all 3 treatment groups. Concentration-effect relation was linear in each treatment group. The plasma procainamide concentrations in group C were significantly greater than in group A; however, the effects on refractoriness and QRS duration were similar in both groups. These findings indicate that with a procainamide dosing method commonly used during electropharmacologic testing, the plasma procainamide concentration decreases significantly during the first 15 minutes after the loading dose is administered.(ABSTRACT TRUNCATED AT 250 WORDS)


The human preference for symmetric walking often disappears when one leg is constrained.
We hypothesized that minimization of metabolic power could drive people to walk asymmetrically when one leg is constrained We studied healthy young adults and independently constrained one or both step lengths to be markedly shorter or longer than preferred using visual feedback When one leg was constrained to take a shorter or longer step than preferred, asymmetric walking patterns were less metabolically costly than symmetric walking patterns When one leg was constrained to take a shorter or longer step than preferred and the other leg was allowed to move freely, most participants naturally adopted an asymmetric gait People may prefer to walk asymmetrically to minimize metabolic power when the function of one leg is constrained during fixed-speed treadmill walking ABSTRACT: The bilateral symmetry inherent in healthy human walking is often disrupted in clinical conditions that primarily affect one leg (e.g. stroke). This seems intuitive: with one leg constrained, gait becomes asymmetric. However, the emergence of asymmetry is not inevitable. Consider that symmetric walking could be preserved by matching the movement of the unconstrained leg to that of the constrained leg. While this is theoretically possible, it is rarely observed in clinical populations. Here, we hypothesized that minimization of metabolic power could drive people to walk asymmetrically when one leg is constrained, even when symmetric walking remains possible. We tested this hypothesis by performing two experiments in healthy adults. In Experiment 1, we constrained one step to be markedly shorter or longer than preferred. We observed that participants could significantly reduce metabolic power by adopting an asymmetric gait (one short/long step, one preferred step) rather than maintaining a symmetric gait (bilateral short/long steps). Indeed, when allowed to walk freely in this situation, participants naturally adopted a less effortful asymmetric gait. In Experiment 2, we applied a milder constraint that more closely approximated magnitudes of step length asymmetry that are observed in clinical populations. Responses in this experiment were more heterogeneous, though most participants adopted an asymmetric gait. These findings support two central conclusions: (1) symmetry is not necessarily energetically optimal in constrained human walking, and (2) people may prefer to walk asymmetrically to minimize metabolic power when one leg is constrained during fixed-speed treadmill walking, especially when the constraint is large.


Enhancement after Small-Incision Lenticule Extraction: Incidence, Risk Factors, and Outcomes.
To report the incidence, risk factors, and outcomes of enhancement after small-incision lenticule extraction (SMILE). Retrospective cohort study. Five hundred twenty-four eyes of 307 patients who underwent SMILE at Singapore National Eye Center between February 2012 and March 2016. The data collected included patient age at primary SMILE, gender, race, preoperative and postoperative manifest refraction spherical equivalent (MRSE), preoperative and postoperative uncorrected distance visual acuity and corrected distance visual acuity, the occurrence of suction loss during the procedure, and the need for enhancement. All enhancements were carried out by performing an alcohol-assisted photorefractive keratectomy (PRK) procedure with application of mitomycin C (MMC). Incidence, prevalence, preoperative and intraoperative risk factors for enhancement, and outcomes after enhancement. The prevalence of enhancement was 2.7%, and 71.4% eyes had enhancement within 1 year of primary SMILE. The incidence of enhancement was 2.1% and 2.9% at 1 and 2 years, respectively. Age older than 35 years, preoperative MRSE more than -6.00 diopters (D), preoperative myopia more than 6.00 D, preoperative astigmatism more than 3.00 D, and intraoperative suction loss were significant risk factors for enhancement after SMILE after adjusting for all other covariates (odds ratios, 5.58, 4.80, 1.41, 3.06, and 2.14, respectively; P = 0.004, 0.021, 0.022, 0.002, and 0.020, respectively). In the patients who underwent bilateral SMILE, the first-operated eye had a marginal trend toward significance for enhancement (P = 0.054). There was no gender or racial difference. In the 14 eyes requiring enhancement, the uncorrected distance visual acuity before enhancement ranged from 20/80 to 20/25, and the mean attempted enhancement spherical equivalent was -0.50±0.86 D. The uncorrected distance visual acuity improved in most patients (92.9%) after enhancement. The 2-year incidence of enhancement after SMILE was 2.9%. Risk factors associated with enhancement included older age at SMILE procedure, greater preoperative MRSE, greater preoperative myopia, greater preoperative astigmatism, and the occurrence of intraoperative suction loss. Clinical outcomes of using PRK with application of MMC for enhancement were good.


Comparison of transperitoneal laparoscopic nephrectomy outcomes in atrophic and hydronephrotic kidneys.
To compare the results of transperitoneal laparoscopic nephrectomy in patients with atrophic and hydronephrotic kidneys. Clinical data were collected from 35 patients who had undergone laparoscopic nephrectomies for atrophic or hydronephrotic non-functioning kidneys between January 2010 and March 2014. Comparative analysis was carried out between the two groups examining demographic characteristics, imaging modalities, etiology, operative times, port numbers, conversion to open surgery, complications, pre-and post-operative hemoglobin and creatinine values, transfusion rates and length of hospital stays. Laparoscopic nephrectomy was performed for atrophic kidneys in 20 (57%) patients and for hydronephrotic kidneys in 15 (42%) patients. In the atrophic group, 3 patients (15%) required transfusion because of bleeding but none of the patients required conversion to open surgery. In the hydronephrotic group one patient (6.6%) required transfusion and conversion to open surgery because of bleeding. Both of the groups were similar in terms of postoperative hospital stay but compared to the atrophic kidneys, hydronephrotic ones were associated with a longer total operative times (90.1 min vs. 73.6 min, p=0.03). Any serious complication (except for bleeding) and mortality were not encountered in both groups. Laparoscopic nephrectomy is a safe and effective minimally invasive technique that can be used in atrophic and hydronephrotic non-functioning kidneys.


Recognition of depression and appropriateness of antidepressant treatment in Italian primary care.
A significant proportion of primary care patients are affected by a depressive disorder and about half of these patients are undetected and undertreated. Twenty-five primary care physicians (PCPs) were recruited in five Italian centres. All consecutive patients who attended the PCPs' clinics in a 2-week period completed the Personal Health Questionnaire (PHQ), and those scoring more than nine on the PHQ were interviewed with the Hamilton Rating Scale for Depression-17 items (HDRS-17). The appropriateness of antidepressant drug treatment was assessed according to the decision to treat, the coverage, the type of drug and the dosage prescribed. The adjusted prevalence for ICD-10 depression in 2093 patients was 18.7%, while the conspicuous morbidity was 10.7%. The ability of PCPs to detect a depression increased proportionally with HDRS scores. The coverage, i. e. the proportion of patients who would benefit from an antidepressant (AD) and who actually received such drugs, was 20.9%. The drugs most frequently prescribed were SSRI (36 %), followed by TCA (21%) and by other AD. Most SSRI were prescribed at therapeutic dosage, while two-thirds of TCA were at sub-therapeutic dosage. About 37% of patients started a non-pharmacological treatment. The severity of depression at the first consultation predicted the persistence of a depressive state in the longer term. The ability of Italian PCPs to detect depression is satisfactory when the patient's depressive state is moderate or severe. The appropriateness of antidepressant drug treatment still needs to be improved.


[The interarm blood pressure difference in the critically ill patient].
To evaluate the prevalence of a difference in systolic blood pressure (SBPd) ≥ 10 mmHg between arms in patients admitted in a Critical Care Unit and to examine the clinical characteristics associated with such blood pressure difference. Observational cross-sectional study. Two blood pressure measurements in each arm were carried out at unit admission. The firstly measured arm was chosen at random. One-hundred and sixty-eight patients were studied, with a mean age of 61 (SD=16), 67.3% male and 45% with a previous hypertension diagnosis. On admission, 27.4% presented SBPd ≥ 10 mmHg. Among them, 54% had higher SBP in the right arm and 46% in the left one. A SBPd ≥ 10 mmHg was associated with a previous hypertension diagnosis (67.4 versus 36.9%; P<.001) and with reduced consciousness (76.1 versus 52.5%; P=.006). Over a quarter of critically ill patients have a SBPd ≥ 10 mmHg between arms. This feature is associated with a previous hypertension diagnosis and reduced consciousness. It should be assessed in the future if the choice of a control arm would help improve patient's care as it would become a more accurate guide for hemodynamic management.


Preoperative albumin-alkaline phosphatase ratio affects the prognosis of patients undergoing hepatocellular carcinoma surgery.
The correlation between the preoperative albuminalkaline phosphatase ratio (AAPR) and the prognosis of hepatocellular carcinoma (HCC) patients after radical resection is still not comprehensive. This study aims to observe the correlation between preoperative AAPR and the prognosis of HCC patients after radical resectionMETHODS: We constructed a retrospective cohort study and included 656 HCC patients who underwent radical resection. The patients were grouped after determining an optimum AAPR cut-off value. We used the Cox proportional regression model to assess the correlation between preoperative AAPR and the prognosis of HCC patients after radical resection. The optimal cut-off value of AAPR for assessing the prognosis of HCC patients after radical resection was 0.52 which was acquired by using X-tile software. Kaplan-Meier analysis curves showed that a low AAPR (⩽ 0.52) had a significantly lower rate of overall survival (OS) and recurrence-free survival (RFS) (P< 0.05). Multiple Cox proportional regression showed that an AAPR > 0.52 was a protective factor for OS (HR = 0.66, 95%CI 0.45-0.97, p= 0.036) and RFS (HR = 0.70, 95% CI 0.53-0.92, p= 0.011). The preoperative AAPR level was related to the prognosis of HCC patients after radical resection and can be used as a routine preoperative test, which is important for early detection of high-risk patients and taking personalized adjuvant treatment.


Chronobiological study on serum innumoreactive gastrin RIA levels in patients with liver cirrhosis.
After days of standardized conditions of life and standardized diets, serum gastrin levels were measured in 6 patients with liver cirrhosis on 3 consecutive days and in 14 normal controls on 1 day. Blood samples were drawn every 4 h. In patients as well as in controls, a significant serum gastrin circadian rhythm was noted. The daily mean serum gastrin levels of patients were not significantly different from those of controls. These results suggest a secondary role of the liver in gastrin metabolism.


Difficult to treat asthma - The importance of thoracic imaging.
Asthma is a chronic disease with clinical variations throughout its course. Periods of symptom aggravation can occur with the need to escalate therapy. Nevertheless, further investigation should be considered when atypical manifestations appear or when worsening of symptoms occurs. Proximal tracheal/bronchial obstruction can mimic symptoms observed in patients with asthma. Primary benign tracheal tumors are rare, but can constitute the cause for such symptoms. We present a case report of a patient with asthma and a tracheal lesion.


Adult hearing-aid users with cochlear dead regions restricted to high frequencies: Implications for amplification.
Cochlear dead regions (DR) are common in adult hearing-aid users, but are usually restricted to high frequencies. The aim was to determine the benefit of high-frequency amplification for ears with and without high-frequency DRs. Participants were fitted with the study hearing aid and tested under four conditions: unfiltered (NAL-NL2 prescription), and low-pass filtered at 1.5, 2, and 3 kHz. VCV stimuli were presented at 65 dB (A) in quiet and in 20-talker babble at a signal-to-babble ratio of 0 dB. Experienced adult hearing-aid users: one group of 18 with a DR edge frequency above 1.5 kHz, and a group of 18 matched controls. Overall performance was best in the unfiltered condition. There was no significant difference in mean performance between the two groups when tested in quiet. However, the DR group obtained less benefit from high-frequency amplification when tested in babble: the mean difference between the unfiltered and 3-kHz filtered condition was 6% and 13% for the DR group and controls, respectively. In adults with a moderate hearing loss and a restricted DR, speech recognition was always best in the unfiltered condition, although mean performance in babble was lower for the DR group.


Circular RNA circERBB2 promotes gallbladder cancer progression by regulating PA2G4-dependent rDNA transcription.
CircRNAs are found to affect initiation and progression of several cancer types. However, whether circRNAs are implicated in gallbladder cancer (GBC) progression remains obscure. We perform RNA sequencing in 10 pairs of GBC and para-cancer tissues. CCK8 and clone formation assays are used to evaluate proliferation ability of GBC cells. qPCR and Western blot are used to determine expression of RNAs and proteins, respectively. CircRNA-protein interaction is confirmed by RNA pulldown, RNA immunoprecipitation, and fluorescence in situ hybridization. We find that circRNA expression pattern is tremendously changed during GBC development. Among dozens of significantly changed circRNAs, a circRNA generated from the oncogene ERBB2, named as circERBB2, is one of the most significant changes. CircERBB2 promotes GBC proliferation, in vitro and in vivo. Other than being a miRNA sponge, circERBB2 accumulates in the nucleoli and regulates ribosomal DNA transcription, which is one of the rate-limiting steps of ribosome synthesis and cellular proliferation. CircERBB2 regulates nucleolar localization of PA2G4, thereby forming a circERBB2-PA2G4-TIFIA regulatory axis to modulate ribosomal DNA transcription and GBC proliferation. Increased expression of circERBB2 is associated with worse prognosis of GBC patients. Our findings demonstrate that circERBB2 serves as an important regulator of cancer cell proliferation and shows the potential to be a new therapeutic target of GBC.


Outpatient antibiotic use and assessment of antibiotic guidelines in Chinese children's hospitals.
Our aim was to investigate outpatient antibiotic use and assess the impacts of intervention in five Chinese children's hospitals from 2002 to 2006. The Anatomical Therapeutical Chemical Classification/Defined Daily Doses and Drug Utilization 90% methodologies were used. We also analyzed the relationship between antibiotic consumption and resistant rate in one of the hospitals. The overall antibiotic consumption decreased during the intervention period in some hospitals, and the variation in use between hospitals was also reduced. A decrease in penicillins and first-generation cephalosporins, and an increase in third-generation cephalosporins as well as in the combinations of penicillins and beta-lactamase inhibitors were observed. In addition, an increasing resistance to antibiotics was a concern due to antibiotic overconsumption. The intervention had effects on the overall antibiotic use in outpatients. However, over the span of 5 years, there was a decrease in the use of narrow-spectrum antibiotics and an increase in broad-spectrum antibiotics.


Selective antagonization of activated Nrf2 and inhibition of cancer cell proliferation by procyanidins from Cinnamomi Cortex extract.
Nuclear factor-E2-related factor 2 (Nrf2) is an important transcription factor and plays a central role in inducible expression of many cytoprotective genes. Recent studies have reported that various cancer cells having unrestrained Nrf2 due to its overexpression exhibit increased proliferation and resistance to chemotherapy. Suppression of abnormal Nrf2 activation is needed for a new therapeutic approach against these cancers. Our previous study found that procyanidins prepared from Cinnamomi Cortex extract (CCE) have an ability to suppress Nrf2-regulated enzyme activity and Nrf2 expression in human lung cancer A549 cells. In the present study, we investigated the effect of CCE procyanidins on Nrf2 activity and cell proliferation in several cancer cells, which have normal or constitutively active Nrf2. Interestingly, CCE procyanidin treatment selectively reduced Nrf2 expression and inhibited cell proliferation in cancer cells that overexpress Nrf2, but these phenomena were not seen in cells with low Nrf2 expression. Moreover, transfection assay demonstrated that CCE procyanidins had selective inhibition of activated Nrf2. These results suggest that CCE procyanidins might be an effective cancer therapeutic agent to selectively suppress abnormal Nrf2 activation responsible for enhanced proliferation.


WITHDRAWN: Development of EMC-based empirical model for estimating spatial distribution of pollutant loads and its application in rural areas of Korea.
The Publisher regrets that this article is an accidental duplication of an article that has already been published in Desalination Water Treat., 27:1-3, 175-188, http://dx.doi.org/10.5004/dwt.2011.2736. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


ALK status testing in non-small cell lung carcinoma: correlation between ultrasensitive IHC and FISH.
ALK gene rearrangements in advanced non-small cell lung carcinomas (NSCLC) are an indication for targeted therapy with crizotinib. Fluorescence in situ hybridization (FISH) using a recently approved companion in vitro diagnostic class FISH system commonly assesses ALK status. More accessible IHC is challenged by low expression of ALK-fusion transcripts in NSCLC. We compared ultrasensitive automated IHC with FISH for detecting ALK status on 318 FFPE and 40 matched ThinPrep specimens from 296 patients with advanced NSCLC. IHC was concordant with FFPE-FISH on 229 of 231 dual-informative samples (31 positive and 198 negative) and with ThinPrep-FISH on 34 of 34 samples (5 positive and 29 negative). Two cases with negative IHC and borderline-positive FFPE-FISH (15% and 18%, respectively) were reclassified as concordant based on negative matched ThinPrep-FISH and clinical data consistent with ALK-negative status. Overall, after including ThinPrep-FISH and amending the false-positive FFPE-FISH results, IHC demonstrated 100% sensitivity and specificity (95% CI, 0.86 to 1.00 and 0.97 to 1.00, respectively) for ALK detection on 249 dual-informative NSCLC samples. IHC was informative on significantly more samples than FFPE-FISH, revealing additional ALK-positive cases. The high concordance with FISH warrants IHC's routine use as the initial component of an algorithmic approach to clinical ALK testing in NSCLC, followed by reflex FISH confirmation of IHC-positive cases.


The fate of adipose tissue and adipose-derived stem cells in allograft.
Utilizing adipose tissue and adipose-derived stem cells (ADSCs) turned into a promising field of allograft in recent years. The therapeutic potential of adipose tissue and ADSCs is governed by their molecular secretions, ability to sustain multi-differentiation and self-renewal which are pivotal in reconstructive, genetic diseases, and cosmetic goals. However, revisiting the existing functional capacity of adipose tissue and ADSCs and their intricate relationship with allograft is crucial to figure out the remarkable question of safety to use in allograft due to the growing evidence of interactions between tumor microenvironment and ADSCs. For instance, the molecular secretions of adipose tissue and ADSCs induce angiogenesis, create growth factors, and control the inflammatory response; it has now been well determined. Though the existing preclinical allograft studies gave positive feedback, ADSCs and adipose tissue are attracted by some factors of tumor stroma. Moreover, allorecognition is pivotal to allograft rejection which is carried out by costimulation in a complement-dependent way and leads to the destruction of the donor cells. However, extensive preclinical trials of adipose tissue and ADSCs in allograft at molecular level are still limited. Hence, comprehensive immunomodulatory analysis could ensure the successful allograft of adipose tissue and ADSCs avoiding the oncological risk.


Classification and diagnosis of dry eye.
Dry eye, or keratoconjunctivitis sicca (KCS), is divided into two subgroups, tear-deficient and evaporative. Each form calls for a different therapeutic approach and it is therefore essential to apply a combination of diagnostic tests in order to establish the exact diagnosis. The diagnosis of KCS is based in part on the patient's history and symptoms and in part on the application of specific tests. Several non-invasive tests exist (e.g. slit-lamp examination, meniscometry, interferometry). Mildly invasive tests are the fluorescein tests, staining with lissamine green, meibometry and meibography. Markedly invasive tests include the Schirmer test and staining with rose bengal. Additional histological procedures are the ocular ferning test and impression cytology. A combination of diagnostic tests leads to one of the two forms of KCS. Its severity is calculated according to grading systems, which exist for several tests. The longitudinal observation of the dry eye patient is provided on the basis of this same grading system, although limited reproducibility is reported for some tests. The diagnostic steps for dry eye patients can be efficiently arranged. In most of the cases, non-invasive or mildly invasive tests provide an accurate diagnosis.


An assessment of the mating motive explanation of the beauty premium in market-based settings.
Labor market and real-life studies were not designed to discriminate between evolutionary and taste-based and stereotype explanations for the beauty premium, have too many confounding effects, and lack crucial information. Smaller-stake and experimental studies provide more compelling evidence in favor of mating motives and suggest the direction of future research for the economists' field studies.


Properties of a new vestibulospinal projection, the caudal vestibulospinal tract.
Neurons in the caudal portions of the medial and descending vestibular nuclei and in vestibular cell group f that project to the cervical or lumbar spinal cord were located by antidromic spinal stimulation. These caudal vestibulospinal tract (CVST) neurons have a median conduction velocity of 12 m/sec, which is well below the conduction velocities of typical lateral or medial vestibulospinal tract (LVST, MVST) axons. The descending fiber trajectories of CVST neurons, determined by comparing thresholds for activation of each neuron from six points in the spinal white matter, were remarkably diverse. Unlike LVST and MVST axons, which are located in the ipsilateral ventral funiculi, CVST axons can be found in both the ventral and dorsolateral funiculi on both sides of the spinal cord. The CVST system is thus both anatomically and physiologically different from the LVST and MVST.


[Anomalies of the vena cava inferior: report on four cases associated with congenital heart disease (author's transl)].
Infrahepatic interruption of the inferior vena cava with azygos continuation has been demonstrated by angiography in three patients; in a fourth case an anomalous venous channel connected the patent azygos vein and the inferior vena cava at the renal level. Cardiac defects were present in all cases.


The Impact of Absorbed Solvent on the Performance of Solid Polymer Electrolytes for Use in Solid-State Lithium Batteries.
The effects of solvent absorption on the electrochemical and mechanical properties of polymer electrolytes for use in solid-state batteries have been measured by researchers since the 1980s. These studies have shown that small amounts of absorbed solvent may increase ion mobility and decrease crystallinity in these materials. Even though many polymers and lithium salts are hygroscopic, the solvent content of these materials is rarely reported. As ppm-level solvent content may have important consequences for the lithium conductivity and crystallinity of these electrolytes, more widespread reporting is recommended. Here we illustrate that ppm-level solvent content can significantly increase ion mobility, and therefore the reported performance, in solid polymer electrolytes. Additionally, the impact of absorbed solvents on other battery components has not been widely investigated in all-solid-state battery systems. Therefore, comparisons will be made with systems that use liquid electrolytes to better understand the consequences of absorbed solvents on electrode performance.


Identification mouse patatin-like phospholipase domain containing protein 1 as a skin-specific and membrane-associated protein.
Patatin-like phospholipase domain containing protein 1 (PNPLA1) mutations have been identified to be associated with autosomal recessive congenital ichthyosis (ARCI) in recent years. However, its molecular characters have not been achieved until now. In the current study, the full length coding cDNA sequence of mouse PNPLA1 (mPNPLA1) was identified firstly. There were several putative transmembrane domains (TMDs) in mPNPLA1 by bioinformation analysis. mPNPLA1 was further found to be expressed exclusively in the membrane fraction in mammalian cells. However, it did not colocalized with the endoplasmic reticulum (ER) or lipid droplets (LDs). Moreover, the mRNA levels of mPNPLA1 was detected to be highly expressed in the skin, while very weak or even less in other mouse tissues by quantitative PCR. In addition, based on experiments with inhibitors and inducer of protein degradation pathways, mPNPLA1 was demonstrated to be degraded by macroautophagy, but not by the proteasome. These results indicated PNPLA1 was a skin-specific and membrane-associated protein for the first time, suggesting that it may mainly play a role in the skin.


The Maternal-to-Zygotic Transition in C. elegans.
In Caenorhabditis elegans, the first zygotic transcription can be detected in the 4-cell stage C. elegans embryo, a little over 2h after fertilization. However, early development until the onset of gastrulation at approximately the 28-cell stage takes place normally even in the absence of zygotic transcription. Therefore, posttranslational and posttranscriptional regulation of the maternal proteins and mRNAs, respectively, that are loaded into the developing oocytes is sufficient to direct development prior to gastrulation. Protein phosphorylation is extensively used throughout the C. elegans maternal-to-zygotic transition (MZT): (1) for maternal protein activation, (2) for coordination of the meiotic and mitotic cell cycle, (3) to mark specific proteins for degradation, and/or (4) to switch the biochemical activity of specific proteins. Maternally loaded mRNAs are regulated primarily by a set of maternal RNA-binding proteins (RBPs), each of which binds to sometimes overlapping target sequences within the mRNA 3'UTRs and either promotes or inhibits translation. Most maternal transcripts are uniformly distributed throughout the embryo but specific transcripts are translated only in certain blastomeres. This control is achieved by the asymmetric distribution of the maternal RBPs, such that the blastomere-specific constellation of RBPs present, and their relative levels, determines the translational readout for their target transcripts. In certain well-studied cases, such as the specification of the sole endodermal precursor in the 8-cell embryo, the maternal transcripts and proteins along with their directly targeted zygotic genes have been identified.


Intravitreal bevacizumab and augmented trabeculectomy for neovascular glaucoma in young diabetic patients.
To report two cases of young diabetic patients with intractable neovascular glaucoma (NVG) who were successfully managed with bevacizumab and mitomycin C-augmented trabeculectomy. Two young patients present with severe NVG secondary to diabetic proliferative retinopathy. The glaucoma was unresponsive to conventional medical therapy and complete panretinal photocoagulation. Both patients underwent augmented trabeculectomy with MMC and intravitreal injection of bevacizumab. Iris rubeosis resolved within 48 h. Both patients have a follow-up period of 6 months and the intraocular pressure (IOP) remain between 10-15 mmHg. Controlling IOP due to NVG in young diabetic patients is difficult and augmented trabeculectomy has a very high failure rate. The addition of intravitreal bevacizumab in the management of NVG particularly in young diabetic patients may improve the success rate of IOP control. It is known that bevacizumab retards neovascularisation. It may also be modulating wound-healing response as well. Bevacizumab may have a potential role in the surgical management of NVG.


Cannabidiol affects breast meat volatile compounds in chickens subjected to different infection models.
No study has demonstrated the use of dietary Cannabis-derived cannabidiol (CBD) to alter the stress response in chickens or examined its effects on meat volatile compounds (VOCs). Here, we subjected chickens to dysbiosis via C. perfringens infection or Escherichia coli lipopolysaccharide (LPS) treatment and investigated the potential link between meat VOCs and cecal bacterial activity and the ameliorative effect of CBD. The cecal bacterial production of short-chain fatty acids (SCFAs) was closely correlated with meat VOCs. CBD supplementation reduced the formation of breast meat spoilage VOCs, including alcohols, trimethylamine and pentanoic acid, in the challenged birds, partly by decreasing cecal putrefactive SCFA production. Meat VOC/cecal SCFA relationships differed according to the challenge, and CBD attenuated the effects of C. perfringens infection better than the effects of LPS challenge on meat VOCs. These findings provide new insights into the interactions among bioactive agent supplementation, gut microbiota activity and meat properties in birds.


Familiarity preference in schizophrenia is associated with ambivalent attitudes towards others.
Preferences or attitudes towards others are often shaped through implicit memory processes, and they serve a critical function in our social lives. Preferences driven by implicit familiarity (mere exposure effect) are particularly important when making judgments about others and forming attitudes of liking and social interaction. In schizophrenia, little is known about the effect of familiarity preference on judgments and attitudes toward others. Subjects included 79 patients with a diagnosis of schizophrenia or schizoaffective disorder and 61 non-patient control subjects. Familiarity preference and trait judgments about others were assessed using a computer task in which neutral faces were rated on positive and negative character traits. "Attractiveness" was rated twice at the beginning and at the end, to measure familiarity preference. Clinical ratings were also obtained. Patients and controls both demonstrated a positive familiarity preference effect. However, the groups differed on the predictive value of familiarity preference for trait judgments. In both groups, the presence of a familiarity preference effect predicted greater positive trait judgments. In patients only, the presence of a familiarity preference effect also predicted, although the correlation was less significant, greater negative trait judgments. The findings are consistent with a preserved familiarity preference effect in individuals with schizophrenia and that the effect is primarily associated with changes in positive attitudes. However, in individuals with schizophrenia this effect is also linked with inferences about negative traits, resulting in ambivalence towards others. This finding may contribute to the impaired social functioning of people with schizophrenia.


[Experience in organization of drug supply for military personnel and military retirees in the United States].
In the U.S. troops and military retirees realize the right to obtain drugs by participating in a nationwide managed care program TRICARE under the routines TRICARE Pharmacy. Militarily, the U.S. health care holding drug based on the Basic Core Formulary and Extended Core Formulary, which are developed by US Department of Defense Pharmacy and Therapeutics Committee. Realization of subprogram TRICARE Pharmacy is performed by Express Scripts.


The perihypoglossal nuclei in the macaque monkey and the chimpanzee.
The topography of the perihypoglossal nuclei (nucleus intercalatus, nucleus prepositus, and nucleus of Roller) of the macaque and the chimpanzee was studied in serial Nissl-stained sections through the brainstem. Maps of the nuclei in the two species are presented. Although in both species the perihypoglossal nuclei are organized according to the general mammalian pattern, they show some particular features, reflecting in part, an increasing phylogenetic differentiation. In the chimpanzee the nucleus prepositus is relatively larger, the nucleus of Roller is more of a separate unit, and its cellular composition is more uniform than is the case in the macaque. A cellular connection between the two nuclei is present in the macaque (even more conspicuous in the cat, apparently absent in man), but is barely discernible in the chimpanzee. A conspicuous difference between the chimpanzee and the macaque concerns the nucleus supragenualis nervi facialis, forming a rostral continuation of the prepositus. In the chimpanzee it is a loosely structured region of small cells (as in the cat and in man). In the macaque, however, it appears as a rather well-delimited column of chiefly medium-sized cells. Some comparative anatomical and functional aspects are discussed. Many contingents of afferents to--and efferents from--the nucleus prepositus have their preferential sites of termination or origin in the nucleus, although with considerable overlapping. This indicates the presence of topical patterns in the prepositus. In general the caudal parts appear to be more related to the cooperation with the cerebellum than the rostral part, whereas the latter appears to be more particularly linked with the oculomotor apparatus.


The administration of lipopolysaccharide, in vivo, induces alteration in L-leucine intestinal absorption.
The objective of the present study was to determine the alterations in L-leucine intestinal uptake by intravenous administration of Lipopolysaccharide (LPS), which is a constituent of gram negative bacterial, causative agent of sepsis. The amino acid absorption in LPS treated rabbits was reduced compared to the control animals. The LPS effect on the amino acid uptake was due to an inhibition of the Na+-dependent system of transport, through both reduction of the apparent capacity transport (Vmax) and diminution of the Na+/K-ATPase activity. The results have also shown that the LPS decreases the mucosal to serosal transepithelial flux and the transport across brush border membrane vesicles of L-leucine. The study of possible intracellular mechanisms implicated in the LPS effect, showed that the second messengers calcium, protein kinase C and c-AMP did not play any role in this effect. However, the absence of ion chloride in the incubation medium removes the LPS inhibition and the intracellular tissue water was affected by the LPS treatment. Therefore, the inhibition in the L-leucine intestinal absorption, by intravenous administration of LPS, could be mainly produced by the secretagogue action of this endotoxin on the gut.


Vitamin B6 deficiency and carcinogenesis.
The literature on the occurrence of carcinogenesis as related to vitamin B6 deficiency is reviewed, and several critical areas, such as altered tryptophan metabolism, impaired immune status, and the metabolism of polyamines are discussed in depth. Preliminary results of vitamin B6-related chemotherapy of malignant melanomas are also presented.


Fructose-induced metabolic syndrome decreases protein expression and activity of intestinal P-glycoprotein.
Metabolic syndrome (MetS) is a health disorder that increases the risk for cardiovascular complications such as heart disease and type 2 diabetes. Some drugs used in patients with MetS are substrates of intestinal P-glycoprotein (P-gp), one of the most important efflux pumps that limit the absorption of xenobiotics. Thus, their bioavailability could be affected by changes in this transporter. Because one of the major causes of MetS in humans is excessive sugar intake, the aim of this study was to evaluate the effect of a fructose-rich diet on intestinal P-gp activity and protein expression in male Sprague-Dawley rats. Fructose-drinking animals received standard chow and 15% (w/v) fructose in the drinking water over 8 wk; control rats were fed on standard chow and tap water. Ileal protein expression of P-gp was 50% lower in fructose-drinking rats than in control animals. This reduction was confirmed by immunofluorescence microscopy. These results correlated well with the decrease of about 50% in the transport rate of the substrate rhodamine 123 in everted intestinal sacs. Finally, an increase of 62% in the intestinal absorption of digoxin, a P-gp substrate used as therapeutic drug, was observed in vivo, in fructose-drinking animals. The present study demonstrated that MetS-like conditions generated by enhanced fructose intake in rats decreased the protein expression and activity of ileal P-gp, thus increasing the bioavailability of P-gp substrates.


Functional properties of purified and reconstituted mitochondrial metabolite carriers.
Eight mitochondrial carrier proteins were solubilized and purified in the authors' laboratories using variations of a general procedure based on hydroxyapatite and Celite chromatography. The molecular mass of all the carriers ranges between 28 and 34 kDa on SDS-PAGE. The purified carrier proteins were reconstituted into liposomes mainly by using a method of detergent removal by hydrophobic chromatography on polystyrene beads. The various carriers were identified in the reconstituted state by their kinetic properties . A complete set of basic kinetic data including substrate specificity, affinity, interaction with inhibitors, and activation energy was obtained. These data closely resemble those of intact mitochondria, as far as they are available from the intact organelle. Mainly on the basis of kinetic data, the asymmetric orientation of most of the reconstituted carrier proteins were established. Several of their functional properties are significantly affected by the type of phospholipids used for reconstitution. All carriers which have been investigated in proteoliposomes function according to a simultaneous (sequential) mechanism of transport; i.e., a ternary complex, made up of two substrates and the carrier protein, is involved in the catalytic cycle. The only exception was the carnitine carrier, where a ping-pong mechanism of transport was found. By reaction of particular cysteine residues with mercurial reagents, several carriers could be reversibly converted to a functional state different from the various physiological transport modes. This "unphysiological" transport mode is characterized by a combination of channel-type and carrier-type properties.


The neglected clubfoot: a salvage procedure.
The study included 18 patients (28 feet), between 4 and 14 years of age. Complete homogeneous correction of the neglected clubfoot was achieved by performing a trapezoid resection osteotomy from the cuboid bone after performing an extensive posteromedial soft-tissue release. The procedure did not sacrifice any articular cartilage and allowed realignment of the forefoot. Tibialis anterior tendon transfer to the cuboid was performed in all feet to eliminate its deforming action and to help maintain the desired degree of correction. A Dwyer calcaneal lateral closing wedge osteotomy was needed in 12 feet and was performed concomitantly with the other procedures. After an average follow-up of 26 months (range 8-31 months) 14 (50%) feet had a good result with normal features, 11 (39.3%) feet had a fair result with definite improvement, and three (10.7%) feet had a poor result with limited improvement. Both good and fair results were considered satisfactory. Patients with tight ligaments were significantly more likely to have a poor outcome (p < .0005). However, neither the patient's age at the time of surgery nor the severity of the deformity was significantly associated with unsatisfactory results. The procedure is strongly recommended in supple feet with resilient ligaments, even in teenagers with severe deformity. In severely deformed rigid feet, the procedure serves to minimize bone resection, thus preventing excessive shortening of the foot if a triple arthrodesis should become necessary at a later date.


Screening and isolation of PHB-producing bacteria in a polluted marine microbial mat.
The characteristics of microbial mats within the waste stream from a seafood cannery were compared to a microbial community at a pristine site near a sandy beach at Puerto San Carlos, Baja California Sur, Mexico. Isolation of poly-beta-hydroxybutyrate (PHB)-producing bacteria, recognition of brightly refractile cytoplasmatic inclusions, lipophilic stains with Sudan Black and Nile Red, and chemical extraction of PHB were used as a culture-dependent strategy for the detection of PHB-producing bacteria. The culture-independent approach included denaturing gradient gel electrophoresis of phylotypes of 16S rRNA of microbial communities from environmental samples. Significant differences in community structure were found among the polluted and pristine sites. These differences were correlated with the physicochemical characteristics of the seawater column. At the polluted site, the seawater was rich in nutrients (ammonia, phosphates, and organic matter), compared to the pristine location. Partial sequencing of 16S rDNA of cultures of bacteria producing PHB included Bacillus and Staphylococcus at both sites; Paracoccus and Micrococcus were found only at the polluted site and Rhodococcus and Methylobacterium were found only at the pristine site. Bands of the sequences of 16S rDNA from both field samples in the denaturing gradient gel electrophoresis (DGGE) analyses affiliated closely only with bacterial sequences of cultures of Bacillus and Staphylococcus. High concentrations of organic and inorganic nutrients at the polluted site had a clear effect on the composition and diversity of the microbial community compared to the unpolluted site.


Monkeypox in human pregnancy: an overview.
Monkeypox is a viral zoonosis caused by the monkeypox virus, an enveloped, double-stranded DNA virus belonging to the Orthopoxvirus genus in the Poxviridae family. Monkeypox has become a disease of global public health significance. Pregnant women are unfortunately among the those at an increased risk for exposure to monkeypox because their immune system is altered during pregnancy. They may also be at risk for more severe disease or a worse outcome than others. During pregnancy or while breastfeeding when consideration is given for pre-exposure or postexposure vaccination, nonreplicating (Modivied Vaccinia Ankara - Bavarian Nordic) or minimally replicating (LC16, KM Biologics) vaccines are preferred. The ACAM2000 vaccine is contraindicated in pregnancy because it contains live virus particles that can cause fetal vaccinia and fetal death. There are no data to support the use of tecovirimat in pregnant women. However, no fetal adverse effects were noticed when tecovirimat was used in animal studies.


Improved quantification limits in chiral capillary electrochromatography by peak compression effects.
The peak compression effect has been applied to improve quantification limits in chiral capillary electrochromatography (CEC). A stationary phase based on the chiral selector vancomycin (Chirobiotic V) was used for separations of the enantiomers of mianserin. By adding solvents with a low dielectric constant, e.g. 2-propanol or tetrahydrofuran, to the sample solution, peak compression could be induced. The plate numbers for the minor enantiomer increased from approximately 100,000 to 1.4-1.6 million plates/m, when the composition of the mobile phase was adjusted so that the analyte eluted within either one of two system zones originating from the sample solution. A 10-fold improvement in the quantification limit for the minor enantiomer was obtained compared to elution under non-focused conditions.


Endostatin binds nerve growth factor and thereby inhibits neurite outgrowth and neuronal migration in-vitro.
Endostatin (ES), the C-terminal fragment of collagen XVIII known for its anti-angiogenic properties, is associated with neurological diseases in mammals. In this study, we investigated the effect of ES on nerve growth factor (NGF)-induced neuronal differentiation, migration, neuritogenesis, and neurite extension. ES partially inhibited PC12 cell differentiation and cerebellar granule cell migration. In addition, neurite outgrowth was inhibited in a concentration-dependent manner. This effect was also matrix-dependent, as we observed better inhibition on PC12 cells grown on collagen compared to laminin matrices. Furthermore, we observed partial NGF depletion by collagen and ES, but not by laminin suggesting that NGF-matrix interactions may be important for promoting neuritogenesis, competitive inhibition by ES or low affinity matrix impairs PC12 differentiation and neurite outgrowth. Finally, using a biosensor technique, we demonstrated a direct interaction between NGF and ES suggesting the mechanism of action of ES may involve NGF sequestration. In conclusion, our study demonstrates the inhibitory effect of ES on different steps of neurogenesis including cell differentiation and migration and neuritogenesis by NGF sequestration. Such sequestration may compromise brain repair following injury, but also may play important role in axon finding as well as a potent therapeutical target in diseases involving abnormal elevated neurotrophic growth factor levels. Taken together, this study raises the consideration of ES as a double-edge sword that carries both deleterious and putative therapeutical effects.


Standard linear plans in single channel high dose rate brachytherapy: a dosimetric analysis.
The use of standard linear plans is proposed for single channel intraluminal High Dose Rate brachytherapy. This technique employs the optimized dwell times derived from a straight line within a curved geometry. Such standardization of the planning procedure ensures expedient delivery of treatment. The 3-D dose distribution resulting from the use of standard linear plans within various curved geometries is investigated. In this study a comparison is made between the dose delivered to the perimeter of the target volume from both standard linear plans and individually optimized plans. Our results demonstrate that the use of a standard linear plan is acceptable in curved geometries, given the current practice of dose and volume specification for high dose rate intraluminal brachytherapy.


Reliability of using a pressure sensor system to measure in-water force in young competitive swimmers.
The aim of this study was to analyze the reliability of using a differential pressure system to measure in-water force in young competitive swimmers. Ten boys and five girls (12.38 ± 0.48 years, 49.13 ± 6.82 kg, 159.71 ± 7.99 cm) were randomly assigned to perform two maximum bouts of 25 m front crawl on different days (trial one, T1; trial two, T2), one week apart. A differential pressure system composed of two hand sensors (Aquanex System, v.4.1, Model DU2, Type A, Swimming Technology Research, Richmond, VA, United States) was used to measure the peak (RFPEAK) and the mean (RFMEAN) resultant force of the dominant and non-dominant hands (in Newton, N). Reliability was analyzed by computing the intraclass correlation coefficient (ICC), typical error (TE), smallest worthwhile change (SWC), coefficient of variation (CV%), standard error of measurement (SEM), and the minimal detectable change (MDC). Bland-Altman plots with 95% limits of agreement were also analyzed. The results showed no differences between T1 and T2 in all variables (p > 0.05). The ICC showed "excellent" reliability (ICC > 0.90) for the RFPEAK and RFMEAN in both hands. The CV% was rated as "good" (<5%) and TE was smaller than SWC in all variables. The Bland-Altman plots showed high reliability with a small bias (RFPEAK dominant, -0.29 N; RFPEAK non-dominant, -0.83 N; RFMEAN dominant, 0.03 N; RFMEAN non-dominant, 0.50 N). The pressure sensor system (Aquanex System) seems to be a reliable device for measuring the hand resultant force during front crawl in young swimmers and can be used to monitor the changes over time.


Unravelling the inhibitory and cytoprotective potential of diuretics towards amyloid fibrillation.
Protein misfolding and deposition of aggregated proteins inside as well as outside of the cells have been associated with several neurotoxic and neurodegenerative disorders like Alzheimer's, Parkinson's and familial amyloid polyneuropathy etc. that could be controlled by anti-aggregation methodologies employing either inhibition or disaggregation of toxic aggregates. Also, the Alzheimer's disease develops in later life is somehow related to the high mid-life blood pressure. Therefore the present work targets the amyloid inhibiting potential of diuretics (a class of antihypertensive drugs) - Indapamide (INDP) and Hydrochlorothiazide (HCTZ) against human serum albumin (HSA) and human lysozyme (HL) fibrillogenesis. The effect of both INDP and HCTZ on the kinetics of amyloid formation of HSA and HL was illustrated and various biophysical techniques like Thioflavin T (ThT) and 8-Anilinonaphthalene-1-sulfonic acid (ANS) fluorescence measurement, Congo red measurements and circular dichroism (CD) measurements depicted the inhibitory action of both INDP and HCTZ in a dose dependent manner. Transmission Electronic Microscopy (TEM) confirmed the absence of fibrillar structures when HSA and HL were co-incubated with INDP and HCTZ. In addition, molecular docking results revealed that both the drugs interacts with HSA and HL through hydrophobic interactions as well as hydrogen bonding, and also showed non-hemolytic activity on human RBCs demonstrated by the Hemolytic assay. Thus, both INDP and HCTZ could be propitious as a therapeutic agent and aid in the cure of amyloid related diseases.


Fine structure of the rabbit submandibular gland during the embryonic development.
The development of the submandibular gland has been examined in rabbit embryos from the 22nd day to the birth. The 2 main types of secretory cells, which synthetize dense serous granules or large pale mucous granules can be identified from the 24th day of development. A third type of cells, characterized by granules having different densities, has been identified in the preterminal tracts. The possibility that these cells are similar to some small cell with an highly dilated endoplasmic reticulum found in adult rabbit submandibular glands is discussed.


The chemical, biological, radiological and nuclear (CBRN) chain of survival: a new pragmatic and didactic tool used by Paris Fire Brigade.


Peripheral LPS administrations up-regulate Fas and FasL on brain microglial cells: a brain protective or pathogenic event?
We evaluated the effect of single or repeated intraperitoneal daily LPS injections on expression of Fas/FasL system within the brain. Results obtained, utilizing real-time quantitative RT-PCR, show that, while a bolus injection of LPS robustly increases hippocampal Fas, but not FasL, mRNA expression, repeated LPS administrations also induce FasL up-regulation. Immunofluorescence studies demonstrated, in turn, an increased number of Fas and FasL immunoreactive microglial cells within the brain parenchyma. The increase in FasL immunoreactivity was, in contrast to Fas, still evident 2 weeks following LPS wash-out. At all times, no Fas-positive immunoreactive neurons nor TUNEL-positive resident brain cells were observed. Collectively, these data provide further support for the existence of innate immune responses in brain and, in addition, raise the possibility that Fas and FasL are, within the brain parenchyma, differentially regulated.


Surgical techniques in short bowel syndrome.
An operation according to Bianchi in a 2-year-old girl is described and indications as well as technical procedure are discussed. The girl was born with a gastroschisis. There was a jejunal perforation 10 cm below the ligament of Treitz caused by a volvulus. Only 20 cm of the jejunum remained. Moreover, only the left part of the colon was present. Total parenteral nutrition for 2 years was necessary. The principle of the operation is based on a longitudinal division of the remaining bowel and a creation of two separate bowel tubes out of the divided bowel halves, thus effecting an isoperistaltic serial connection by means of two anastomoses. This is technically possible since each half of the bowel wall has its own blood supply. The vessels originating from the mesenterium branch off before they reach the bowel wall so that the mesenteric dissection line can be anastomosed longitudinally with the antimesenteric border. This results in doubling of the bowel length, narrowing of the preoperatively dilated bowel diameter, closer contact of bowel contents with the mucosa, prolonged transit time and a Bacteroides colonization which is reduced by more effective peristalsis. Indications, time of operation and our own experiences are discussed and three cases are described. All children are alive and show marked improvement in nutrition.


Outcomes of recurrent stroke in patients with atrial fibrillation according to presumed etiology.
Atrial fibrillation (AF) is a potent risk factor for stroke. The presence of competing etiologies can modify disease outcomes and demand different treatment strategies. The primary purpose of the study was to examine the differences in outcomes for patients with AF admitted with a recurrent stroke, stratified according to the presumed etiology of the stroke. We analyzed AF patients admitted for a recurrent ischemic stroke in an academic comprehensive stroke center. Recurrent strokes were categorized as "Cardioembolic", meaning AF without any competing mechanism, versus "Undetermined" etiology due to competing mechanisms. We used logistic regression to test the association between recurrent stroke etiology and favorable outcome (discharge home), after accounting for important covariates. We included 230 patients, with a mean age 76.9 (SD ± 11.3), 52.2% male, median National Institute of Health Stroke Scale (NIHSS) score of 7 (IQR 2-16). Patients with cardioembolic stroke (65.2%) had higher median NIHSS 8.5 (3-18) versus 3 (1-8) and were more likely to be treated with reperfusion therapies. The favorable outcome was reached by 64 patients (27.8%), and in-hospital mortality was 15.2% overall. After adjustment, there was no difference in outcome between patients with cardioembolic versus undetermined stroke etiology (odds ratio for discharge home: 1.41; 95% CI: 0.65-3.15). In this single-center sample of AF patients with history of stroke, there was no difference in discharge outcomes between those with cardioembolic and those with undetermined stroke etiology. This question warrants examination in larger samples to better understand the importance of the stroke mechanism and secondary prophylaxis.


Ontogeny of melanophore patterns in haploid and diploid embryos of the frog, Bombina orientalis.
Diploid tadpoles of the discoglossid frog, Bombina orientalis, possess a distinctive rectangular network of epidermal melanophores. The ontogeny of this network was examined and utilized as a model for the comparison of tissue integrity and cellular interactions in diploid and haploid embryos. During the process of network formation in diploids, a variety of melano-phore-melanophore interactions was observed. These included temporary contacts between neighboring melanophore processes, deviations of processes toward neighboring melanophores, and lateral extensions between closely situated, parallel processes originating from different cell bodies. None of these intercellular interactions were seen in haploid embryos. Haploid melanophores displayed fewer cytoplasmic extensions, appeared to be randomly oriented, and failed to establish the ordered network seen in diploid embryos. It was also discovered that, in comparison with diploid tissues, relative densities of melanophores and epithelial cells were not uniformly regulated in haploid embryos. These findings are interpreted as indicating that haploid embryos possess fundamental cell and tissue defects, and that the "haploid syndrome" is likely based on more than one or a few defective physiological functions.


The free flap based on a single proximal perforator of the radial artery: ultrasonography study and clinical applications in reconstruction of soft tissue defects in finger.
To locate an anastomosable constant perforator of the radial artery on the proximal forearm using ultrasonography and describe the application of a free radial artery flap based on a single proximal perforator for the reconstruction of soft tissue defects in finger. In 20 forearms (ten right and ten left) from ten volunteers, the perforators in the proximal half of the forearm from the radial artery were visualized using ultrasonography. The free radial artery perforator flaps based on the single perforator were used to reconstruct digital soft tissue defects in four cases between October 2017 and May 2018. Of the 20 forearms, an anastomosable perforator was consistently detected in the radial artery in the forearm's proximal half. The perforator diameter was 0.7 ± 0.1 mm, and the pedicle length was 12 ± 3 mm according to ultrasonography. The perforator's location was far from the elbow crease (8.8 ± 1.4 cm), and the relative distance of the perforator's location from the elbow crease to the wrist crease was 37.2% ± 4.8%. In clinical cases, all flaps survived. Flap size ranged from 3.5 to 6.5 cm in length and 2.3-3.0 cm in width. Donor sites of the forearm were closed primarily in all cases. During a mean period of 12 months (8-14 months) follow-up, the average static 2-PD was 13.8 mm (10-18 mm) in the flap area, and the ROM of DIP was 35° (30-40°), PIP was 82° (45-110°), and MP was 85° (70-90°) of the affected finger. The mean Brief Michigan Hand Questionnaire (BMHQ) score was 72.9 (60.4-85.4) in the affected hand. An anastomosable perforator is consistently located on the radial artery in the proximal half of the forearm. The free radial artery flap based on this single perforator provides acceptable functional and cosmetic outcomes for reconstructing digital soft tissue defects. With the preservation of the forearm's main vessel (radial artery), this flap provides another reliable option for hand surgeons to reconstruct small soft tissue defects in finger.


Comparison of membrane proteins from benign and malignant human thyroid tissues by two-dimensional polyacrylamide gel electrophoresis.
In this study two-dimensional (2D) polyacrylamide gel electrophoresis with silver staining was used to analyze cellular membranous proteins of various normal and pathological human thyroid tissues. The aim was to understand the differences in cellular membranous proteins between these tissues, which would aid in the differential diagnosis of thyroid malignancy. Characteristic protein spots had a molecular mass of 50-64 kDa and a pI of 5.7-6.5. There were two groups of isoform protein spots in this area. The higher-molecular-mass group was found in follicular thyroid cancer tissues which and was not visible in normal thyroid tissues. The low-molecular-mass group was found in follicular carcinoma or adenoma tissues and was detected in one to three spots. The papillary thyroid carcinoma tissues gave different 2D gel maps. There were few spots of papillary thyroid carcinoma tissue membranous proteins within the examined area. The 2D gel maps may be used for differential diagnosis of follicular neoplasm. The characteristics of these protein spots require further investigation.


Simultaneously ultrasensitive and quantitative detection of influenza A virus, SARS-CoV-2, and respiratory syncytial virus via multichannel magnetic SERS-based lateral flow immunoassay.
Respiratory viruses usually induced similar clinical symptoms at early infection. Herein, we presented a multichannel surface-enhanced Raman scattering-based lateral flow immunoassay (SERS-based LFA) using high-performance magnetic SERS tags for the simultaneous ultrasensitive detection of respiratory viruses, namely influenza A virus (H1N1), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) in biological samples. As-prepared magnetic SERS tags can directly enrich and capture target viruses without pretreatment of samples, avoiding the interference of impurities in the samples as well as improving the sensitivity. With the capture-detection method, the detection limits of the proposed assay reached 85 copies mL-1, 8 pg mL-1, and 8 pg mL-1 for H1N1, SARS-CoV-2 and RSV, respectively. Moreover, the detection properties of the proposed method for target viruses in throat swab samples were verified, suggesting its remarkable potential for the early and rapid differential diagnosis of respiratory viruses.


Dyslipidemia in renal transplant recipients treated with a sirolimus and cyclosporine-based immunosuppressive regimen: incidence, risk factors, progression, and prognosis.
This retrospective study compared the incidence, severity, and predisposing factors for dyslipidemia among renal transplant patients treated for up to 6 years with a cyclosporine +/- prednisone-based concentration-controlled regimen without (n=118) or with (n=280) ascending exposures to sirolimus. The diagnosis of dyslipidemia was established when the serum cholesterol value (CHO) was more than 240 mg/dL or serum triglycerides (TG) were more than 200 mg/dL. Generalized estimating equations and mixed-modeling procedures were used for statistical analyses. Hypercholesterolemia was observed in 46% to 80% and hypertriglyceridemia in 43% to 78% of sirolimus-treated patients during the first 6 posttransplantation months. The mean peak serum lipid levels among patients in the sirolimus group (CHO=285.5 mg/dL; TG=322.4 mg/dL) were significantly higher than those in the nonsirolimus group (CHO=250.2 mg/dL and TG=267.6 mg/dL; both P<0.01). The lipid values, which were persistently elevated during the first posttransplantation year, decreased slowly thereafter but remained significantly higher than the pretransplantation levels beyond 4 years after transplantation. The two forms of hyperlipidemia tended to occur in parallel (Pearson's coefficient of correlation, r=0.5, P<0.001), showing a positive predictive value of 0.67 and a negative predictive value of 0.65. However, there was no significant difference in the incidence of cardiovascular events within 4 years after transplantation among patients treated with versus without sirolimus. The dyslipidemia associated with sirolimus therapy, albeit persistent, does not seem to represent a major risk factor for the early emergence of cardiovascular complications.


A randomized Phase III trial of etoposide, epirubicin, and cisplatin versus 5-fluorouracil, epirubicin, and cisplatin in the treatment of patients with advanced gastric carcinoma. Turkish Oncology Group.
Gastric carcinoma is a substantial health problem in Turkey, and the majority of patients present with inoperable disease. The aim of this randomized trial was to assess the activity of 5-fluorouracil versus etoposide when combined with epirubicin plus cisplatin in patients with advanced gastric carcinoma (AGC). In this prospective, randomized, multicenter Phase III study, previously untreated patients with histopathologically proven AGC enrolled after giving informed consent. Patients were allocated to receive either EEP (etoposide 120 mg/m2, epirubicin 30 mg/m2, and cisplatin 40 mg/m2 on Days 1 and 8) or FEP (5-fluorouracil 600 mg/m2, epirubicin 60 mg/m2, and cisplatin 80 mg/m2 on Day 1), and the regimens were to be repeated every fourth week. Of a total of 131 eligible patients, 64 were in the EEP group and 67 were in the FEP group. The objective response (complete + partial) rates for evaluable patients (n = 118) were comparable (P = 0.63) in the EEP (20.3%, 12/59) and FEP (15.3%, 9/59) groups, respectively. Actuarial analyses revealed comparable median progression free survival (6 vs. 7 months, P > 0.05) and overall survival (6 vs. 5 months, P > 0.05) duration in the EEP and FEP groups. Both regimens were well tolerated. The most common toxicity was Grade 1-2 nausea with or without vomiting. No chemotherapy-related death occurred. The current study resulted in inadequate response rates for EEP and FEP regimens. Neither combination, as used at the doses and schedules in this study, can be recommended as standard treatment for patients with AGC.


Isolation and properties of lead-resistant variants of rat glioma cells.
Glial cells are thought to protect neurons from heavy-metal toxicity. To gain a better understanding of mechanisms of protection against lead compounds, a number of lead-resistant C6 rat glioma cell sublines have been isolated. After 8 mo of growth in the absence of lead nitrate, three sublines still maintain their lead-resistant phenotype. None of the lead-resistant sublines are cross-resistant to Cd(II) or Ni(II), but all are cross-resistant (in varying degrees) to Hg(II), As(III), Sb(III), and Sn(II), and one is resistant to trimethyl tin. No inducible lead resistance is seen in any glioma line. One subline has been used to create cell-cell hybrids with wild-type cells. The hybrids exhibit dominance of the lead-resistant phenotype. To identify and analyze altered gene expression at the mRNA level in the lead-resistant sublines, the differential display technique was used. Numerous differences are seen between amplified fragments from wild-type and lead-resistant cells. Candidate clones are now being analyzed to confirm the differential expression and to isolate cDNAs that confer lead resistance.


Endoscopic diverticulotomy of Zenker's diverticulum: management and complications.
Two approaches can be used for treating Zenker's diverticulum operatively: external or endoscopic. The records of 52 patients who underwent Zenker's diverticulum endoscopically were evaluated retrospectively. Twenty-two patients were treated with endoscopic scissors and 30 patients by carbon dioxide laser resection. The therapeutic concept of rigid endoscopic diverticulotomy was appraised with respect to the intraoperative and postoperative management for treatment and prevention of complications. Forty-four of 52 patients were free of symptoms and 8 patients (15.4%) had a recurrence, 4 of which were within 4 months. Except for 2 cases, the recurrences could be reoperated endoscopically. The complication rate was 13.5% with hemorrhage the most common complication (3 cases). Two cases required an external approach to control severe bleeding. The endoscopic approach for Zenker's diverticulum is safe and effective if the surgeon is prepared to handle extraordinary complications, such as severe hemorrhage, quickly and sufficiently.


Compression of common peroneal nerve caused by an extraneural ganglion cyst mimicking intermittent claudication.
Peripheral neuropathies caused by ganglion cysts are rare. They seldom cause serious complications especially in the lower extremities. The case was a 51-year-old woman referred by her physician to the vascular surgeon with diagnosis including intermittent (vascular) claudication and deep venous thrombosis. Primarily vascular surgeon performed a doppler ultrasound of the lower extremity and calculation of the ankle-brachial index. There were no abnormal pathological findings. Careful physical examination revealed soft swelling and tenderness around the fibular head and neck. Weakness was observed in foot eversion and dorsiflexion. There was pain and tingling in the distribution of the peroneal nerve. and referring the patient to orthopedic surgeon owing to concern for a potential compressive lesion at the right proximal tibiofibular region. Electromyogram studies and physical examination confirmed a diagnosis of compression neuropathy of common peroneal nerve. Magnetic resonance imaging revealed a fluid-filled, lobulated mass indicating a ganglion cyst. One months after decompression, the patient had no complaint. Fast diagnosis and immediate management are essential to regain best possible recovery.


Cell kinetic classification of tumors of the nervous system by DNA precursor labeling in vitro.
We studied 142 excisional or needle biopsy specimens of nervous system tumors with tritiated thymidine or 5'-bromodeoxyuridine (BrdUrd). Either precursor gave similar results. A labeling index (LI), expressed as a percentage and representing the S-phase fraction, was measured by a microscopic count from stained sections. The in vitro method ranked mean and median LIs of different neoplasms similarly to reported results from the in vivo administration of BrdUrd and reflected clinical aggressiveness of various tumor types. Gliosis, myxopapillary ependymomas, benign meningiomas, neurilemmomas, and pituitary adenomas consistently showed LIs less than 1%. The LI of a cerebellar Lhermitte-Duclos gangliocytoma was zero, indicating the virtual absence of proliferation. Mean LIs and standard deviations of other tumors were as follows: anaplastic astrocytomas, 3.07% +/- 2.98%; glioblastoma multiforme, 6.15% +/- 5.61%; non-Hodgkin's lymphoma, 12% +/- 9.5%; and metastatic neoplasms, 15% +/- 8.5%. The survival rate of patients with astrocytic tumors was inversely proportional to the LI. We conclude that the in vitro method is a practical alternative to in vivo BrdUrd administration for measurement of S-phase cells in tumors of the nervous system that gives prognostically useful information. Combination of BrdUrd LI with growth fraction measurement by monoclonal antibodies could offer new insights into brain tumor cell kinetics.


Accumulation of lysophosphatidylinositol in RAW 264.7 macrophage tumor cells stimulated by lipid A precursors.
N2,O3-Diacylglucosamine 1-phosphate (lipid X), a monosaccharide precursor of Escherichia coli lipid A, was used to stimulate RAW 264.7 macrophage tumor cells, and the effects on macrophage phospholipid metabolism were examined. The addition of E. coli lipid X to the medium of cells that had been uniformly labeled with 32Pi resulted in a 4-8-fold increase in the level of lysophosphatidylinositol. This effect was maximal at 5 microM lipid X. Lysophosphatidylinositol levels reached a maximum 45 min after stimulation, followed by a gradual decline to near normal levels within 2 h. The formation of lysophosphatidylinositol was dependent upon extracellular calcium and was almost completely inhibited when cycloheximide was added at the time of stimulation. The addition of the disaccharide lipid A precursor IVA, commercial lipopolysaccharide (1 microgram/ml), phorbol 12-myristate 13-acetate (10(-7) M), or calcium ionophore A23187 (10(-6) M) to these cells resulted in a similar increase in lysophosphatidylinositol levels, but phosphatidic acid was inactive. The stimulation by IVA and phorbol myristate acetate was blocked by cycloheximide, but the stimulation by lipopolysaccharide was only partially blocked. The stimulation by A23187 was unaffected by cycloheximide. The increase in lysophosphatidylinositol levels might be related to the stimulation of arachidonate release and prostaglandin synthesis that is also observed in cells treated with lipid A precursors. The disaccharide precursor, IVA, was at least 100 times more effective than lipid X at stimulating lysophosphatidylinositol formation and prostaglandin release. The relative ability of lipid X and IVA to stimulate these cells correlated well with their effects on other lipopolysaccharide-responsive systems. Macrophage tumor cells also had the ability to inactivate lipid X by dephosphorylating it.


Von Willebrand disease mutation spectrum and associated mutation mechanisms.
Von Willebrand disease (VWD) is a bleeding disorder that is mainly caused by mutations in the multimeric protein von Willebrand factor (VWF). These mutations may lead to deficiencies in plasma VWF or dysfunctional VWF. VWF is a heterogeneous protein and over the past three decades, hundreds of VWF mutations have been identified. In this review we have organized all reported mutations, spanning a timeline from the late eighties until early 2017. This resulted in an overview of 750 unique mutations that are divided over the VWD types 1, 2A, 2B, 2M, 2N and 3. For many of these mutations the disease-causing effects have been characterized in vitro through expression studies, ex vivo by analysis of patient-derived endothelial cells, as well as in animal or (bio)physical models. Here we describe the mechanisms associated with the VWF mutations per VWD type.


Antitumor activity of didemnin B in the human tumor stem cell assay.
In vitro studies of the schedule dependency and cytotoxicity of didemnin B, a novel depsipeptide isolated from a Carribean tunicate (Didemnidae), were carried out in fresh tumor cells obtained from biopsies from 39 cancer patients using the human tumor stem cell assay. Two schedules of drug exposure were examined (1 h and continuous exposure in the agar). Tumor cells from nine of 26 patients (34.6%) showed reduced survival of tumor-colony forming units to 30% of control or less at the 0.01 microgram level in the continuous exposure studies. Cells from eight of 17 patients (47%) showed a similar degree of sensitivity to didemnin after a 1-h exposure to 0.1 microgram prior to plating. The median ID50 values were 4.2 X 10(-3) micrograms/ml and 46 X 10(-3) micrograms/ml for continuous and 1-h exposures, respectively. A clear dose-response relationship was observed with both dosage schedules. Comparison of the slopes of the continuous and 1-h exposures and of the ID50 of the drug schedules suggests that didemnin is a cell-cycle-non-specific cytotoxic agent. Significant in vitro antitumor activity was observed at low concentrations against carcinomas of the breast, ovary, and kidney, and also mesothelioma and sarcoma. These results can provide pharmacologic goals to be achieved in phase I clinical trial. Further in vitro testing should help select tumor types for study in phase II trials of this very promising new anticancer drug.


[What is confirmed in the treatment of chronic kidney disease?]
Chronic kidney disease (CKD) is defined as a relevant excretion of albumin into the urine or a reduction of the glomerular filtration rate (GFR) over a longer time period of ≥ 3 months. The causes of CKD are manifold, whereby the association with diabetes mellitus is the most frequent cause. Early stages of CKD affect approximately 10% of the total population. The frequency of cardiovascular events, the risk of dependency on dialysis and the all-cause mortality increase exponentially with a decrease in the GFR and an increase in albuminuria. The guidelines of the German College of General Practitioners and Family Physicians (DEGAM) and the organization Kidney Disease: Improving Global Outcomes (KDIGO) recommend referral to a nephrologist with a GFR of ≤ 30 or ≤ 60 ml/min/1.73 m2 in the presence of various cofactors. This means that the majority of CKD patients are treated by general internists or general practitioners. This article gives a concise summary of current data on the treatment of CKD and its associated complications in clinical practice. It refers to the current guidelines and also new study results which could perspectively expand the therapeutic repertoire.


Cardiac Adaptation of the Maternal Heart During Pregnancy: A Color-Coded Tissue Doppler Imaging Study--Feasibility, Reproducibility and Course during Pregnancy.
Tissue Doppler imaging (TDI) allows the noninvasive quantification of global and regional myocardial function. Since there are changing loading conditions during pregnancy, this study aimed to determine maternal myocardial adaptation in normal pregnancy with TDI and tracking of the heart cycle. 106 pregnant women, mean age of 33.4 years at baseline, prospectively underwent a total of 161 color-coded tissue Doppler echocardiography samples throughout pregnancy. In further offline analysis of the global and regional myocardial function of the basal segments, maximum tissue velocities at systole (Sm), in the early filling phase of diastole (Em) and during atrial contraction (Am) were assessed. From those stored samples, S-wave, E-wave and A-wave velocities could be obtained with a feasibility of 94.8 % and with good inter- and intra-observer variability. S-wave velocity first showed an increase during early pregnancy followed by a decline to baseline characteristics at the 3 rd trimester. The E-wave velocity declined throughout pregnancy. The A-wave velocity increased continuously. These alterations result in a continuous decline of Em/Am ratio as pregnancy advances. Alterations in tissue velocities during pregnancy reflect maturational changes that mimic "diastolic dysfunction". Based on an understanding of those normal physiological changes, TDI may therefore assist in the monitoring and/or detecting of subclinical myocardial dysfunction during pregnancy.


Body painting to promote self-active learning of hand anatomy for preclinical medical students.
The purpose of this study was to use the body painting method to teach hand anatomy to a group of preclinical medical students. Students reviewed hand anatomy using the traditional method and body painting exercise. Feedback and retention of the anatomy-related information were examined by a questionnaire and multiple-choice questions, respectively, immediately and 1 month after the painting exercise. Students agreed that the exercise was advantageous and helped facilitate self-active learning after in-class anatomy lessons. While there was no significant difference in knowledge retention between the control and experimental groups, the students appreciated the exercise in which they applied body paint to the human body to learn anatomy. The body painting was an efficient tool for aiding the interactive learning of medical students and increasing the understanding of gross anatomy.


Patients with hepatic breast cancer metastases demonstrate highly specific profiles of matrix metalloproteinases MMP-2 and MMP-9 after SIRT treatment as compared to other primary and secondary liver tumours.
Patients with primary and metastatic liver malignancies represent a highly heterogeneous patient pool characterised by some of the shortest life expectancies amongst oncology patients. Investigation and better understanding of liver malignancies is an emerging field which requires high-quality multidisciplinary research and collaboration. A study of 158 patients with primary hepatic carcinomas and secondary liver metastases, altogether 15 cancer types of different origin, who underwent selective internal radiation therapy (SIRT) with Yttrium(90) or transarterial chemoembolisation, was undertaken in an effort to detect distinguishing features with respect to activity profiles of both blood matrix metalloproteinase (MMP-2 and MMP-9). Noteworthy, stratification of all hepatic cancer groups with respect to MMP-2 and MMP-9 activities revealed characteristic patterns specifically in patients with hepatic breast cancer metastases who had undergone SIRT. In contrast to all other groups, these patients demonstrated well-consolidated profiles of both MMPs, reflecting a common feature, namely an immediate and durable increase of their activity after the SIRT treatment. Although the total number of patients in the breast cancer group is relatively small (15 patients), since increased activities of MMP-2 and MMP-9 are well known prognostic factors for poor outcomes of oncologic patients, the significance and clear group-specificity (from 15 ones investigated here) of this previously unanticipated finding requires particular attention and further investigations. Particularly important is to determine, whether this increase of the metalloproteinase activity was provoked by SIRT, as well as whether special selection criteria are required for patients with breast cancer metastases to the liver who are being considered for SIRT. It is recommended that a more focused, multidisciplinary and large-scaled investigations of the possible adverse effects of SIRT in patients with advanced metastatic disease of breast cancer be undertaken, with an appropriate patients' stratification, set-up of the relevant patient profiles and disease modelling.


Simple, reliable and inexpensive telemetry system for continuous monitoring of small animal core temperature.
A core temperature telemetry system is described which includes a transmitter and circuitry for signal reception, noise elimination and computer interfacing. The system is inexpensive (less than $50), easily constructed, reliable, portable, and has proven to be sensitive to rapid fluctuations in core temperature.


Intermittent post-exercise sauna bathing improves markers of exercise capacity in hot and temperate conditions in trained middle-distance runners.
This study investigated whether intermittent post-exercise sauna bathing across three-weeks endurance training improves exercise heat tolerance and exercise performance markers in temperate conditions, compared to endurance training alone. The subsidiary aim was to determine whether exercise-heat tolerance would further improve following 7-Weeks post-exercise sauna bathing. Twenty middle-distance runners (13 female; mean ± SD, age 20 ± 2 years, [Formula: see text]O2max 56.1 ± 8.7 ml kg-1 min-1) performed a running heat tolerance test (30-min, 9 km h-1/2% gradient, 40 °C/40%RH; HTT) and temperate (18 °C) exercise tests (maximal aerobic capacity [[Formula: see text]O2max], speed at 4 mmol L-1 blood lactate concentration ([La-]) before (Pre) and following three-weeks (3-Weeks) normal training (CON; n = 8) or normal training with 28 ± 2 min post-exercise sauna bathing (101-108 °C, 5-10%RH) 3 ± 1 times per week (SAUNA; n = 12). Changes from Pre to 3-Weeks were compared between-groups using an analysis of co-variance. Six SAUNA participants continued the intervention for 7 weeks, completing an additional HTT (7-Weeks; data compared using a one-way repeated-measures analysis of variance). During the HTT, SAUNA reduced peak rectal temperature (Trec; - 0.2 °C), skin temperature (- 0.8 °C), and heart rate (- 11 beats min-1) more than CON at 3-Weeks compared to Pre (all p < 0.05). SAUNA also improved [Formula: see text]O2max (+ 0.27 L-1 min-1; p = 0.02) and speed at 4 mmol L-1 [La-] (+ 0.6 km h-1; p = 0.01) more than CON at 3-Weeks compared to Pre. Only peak Trec (- 0.1 °C; p = 0.03 decreased further from 3-Weeks to 7-Weeks in SAUNA (other physiological variables p > 0.05). Three-weeks post-exercise sauna bathing is an effective and pragmatic method of heat acclimation, and an effective ergogenic aid. Extending the intervention to seven weeks only marginally improved Trec.