Overexpression of CDC25B and LAMC2 mRNA and protein in esophageal squamous cell carcinomas and premalignant lesions in subjects from a high-risk population in China.
Molecular events associated with the initiation and progression of esophageal squamous cell carcinoma (ESCC) remain poorly understood but likely hold the key to effective early detection approaches for this almost invariably fatal cancer. CDC25B and LAMC2 are two promising early detection candidates emerging from new molecular studies of ESCC. To further elucidate the role of these two genes in esophageal carcinogenesis, we did a series of studies to (a) confirm RNA overexpression, (b) establish the prevalence of protein overexpression, (c) relate protein overexpression to survival, and (d) explore their potential as early detection biomarkers. Results of these studies indicated that CDC25B mRNA was overexpressed (>/=2-fold overexpression in tumor compared with normal) in 64% of the 73 ESCC cases evaluated, whereas LAMC2 mRNA was overexpressed in 89% of cases. CDC25B protein expression was categorized as positive in 59% (144 of 243) of ESCC cases on a tumor tissue microarray, and nonnegative LAMC2 patterns of protein expression were observed in 82% (225 of 275) of cases. Multivariate-adjusted proportional hazard regression models showed no association between CDC25B protein expression score and risk of death [hazard ratio (HR) for each unit increase in expression score, 1.00; P = 0.90]; however, several of the LAMC2 protein expression patterns strongly predicted survival. Using the cytoplasmic pattern as the reference (the pattern with the lowest mortality), cases with a diffuse pattern had a 254% increased risk of death (HR, 3.52; P = 0.007), cases with no LAMC2 expression had a 169% increased risk of death (HR, 2.69; P = 0.009), and cases with a peripheral pattern had a 130% greater risk of death (HR, 2.30; P = 0.02). CDC25B protein expression scores in subjects with esophageal biopsies diagnosed as normal (n = 35), dysplastic (n = 23), or ESCC (n = 32) increased significantly with morphologic progression. For LAMC2, all normal and dysplastic patients had a continuous pattern of protein expression, whereas all ESCCs showed alternative, noncontinuous patterns. This series of studies showed that both CDC25B and LAMC2 overexpress RNA and protein in a significant majority of ESCC cases. The strong relation of LAMC2 pattern of protein expression to survival suggests a role in prognosis, whereas the association of CDC25B with morphologic progression indicates a potential role as an early detection marker.


Analysis of neuroretinal rim distribution and vascular pattern in eyes with presumed large physiological cupping: a comparative study.
To investigate possible differences in neuroretinal rim distribution, vascular pattern, and peripapillary region appearance between eyes with presumed large physiological optic disc cupping (pLPC) and eyes with minimal optic disc excavation. We prospectively enrolled consecutive subjects with pLPC and individuals with minimal excavation (optic disc excavation within normal limits; control group). All eyes had normal visual fields and untreated intraocular pressure (IOP) <21 mmHg. Eyes with pLPC required vertical cup-to-disc ratio (VCDR) ≥ 0.6 and ≥ 30 months of follow-up with no evidence of glaucomatous neuropathy. For controls, VCDR was limited to ≤ 0.5. We compared ocular signs and characteristics related to the neuroretinal rim distribution, vascular pattern, peripapillary region appearance and disc size between groups. Whenever both eyes were eligible, one was randomly selected for analysis. A total of 74 patients (mean age, 45.6 ± 14.9 years) with pLPC and 45 controls (mean age, 44.8 ± 11.6 years) were enrolled (p = 0.76). Median disc size and VCDR was significantly larger in eyes with pLPC compared to controls (p < 0.01). The proportion of eyes with violation of the ISNT rule, laminar dot sign, nasal shifting of the central vessels, nasal excavation and baring of circumlinear vessel was significantly greater in the eyes with pLPC compared to controls (p < 0.01). There were no significant differences regarding the proportions of eyes with peripapillary atrophy between groups (p < 0.09). Finally, disc size was significantly associated with VCDR (r(2) = 0.47, p < 0.01), with an increase of 0.21 in VCDR for each 1 mm(2) in disc area. Compared to normal controls, eyes with pLPC may present a higher proportion of optic nerve head findings frequently observed in glaucomatous eyes. This seems to be explained in part by the larger discs found in these eyes. We believe care should be taken while classifying them as glaucomatous or not based solely on these characteristics.


Cirrus Airframe Parachute System and Odds of a Fatal Accident in Cirrus Aircraft Crashes.
General aviation (GA) accidents have continued to demonstrate high fatality rates. Recently, ballistic parachute recovery systems (BPRS) have been introduced as a safety feature in some GA aircraft. This study evaluates the effectiveness and associated factors of the Cirrus Airframe Parachute System (CAPS) at reducing the odds of a fatal accident in Cirrus aircraft crashes. Publicly available Cirrus aircraft crash reports were obtained from the National Transportation Safety Board (NTSB) database for the period of January 1, 2001-December 31, 2016. Accident metrics were evaluated through univariate and multivariate analyses regarding odds of a fatal accident and use of the parachute system. Included in the study were 268 accidents. For CAPS nondeployed accidents, 82 of 211 (38.9%) were fatal as compared to 8 of 57 (14.0%) for CAPS deployed accidents. After controlling for all other factors, the adjusted odds ratio for a fatal accident when CAPS was not deployed was 13.1. The substantial increased odds of a fatal accident when CAPS was not deployed demonstrated the effectiveness of CAPS at providing protection of occupants during an accident. Injuries were shifted from fatal to serious or minor with the use of CAPS and postcrash fires were significantly reduced. These results suggest that BPRS could play a significant role in the next major advance in improving GA accident survival.Alaziz M, Stolfi A, Olson DM. Cirrus Airframe Parachute System and odds of a fatal accident in Cirrus aircraft crashes. Aerosp Med Hum Perform. 2017; 88(6):556-564.


Managing risk: clinical decision-making in mental health services.
Risk assessment and management is a major component of contemporary mental health practice. Risk assessment in health care exists within contemporary perspectives of management and risk aversive practices in health care. This has led to much discussion about the best approach to assessing possible risks posed by people with mental health problems. In addition, researchers and commentators have expressed concern that clinical practice is being dominated by managerial models of risk management at the expense of meeting the patient's health and social care needs. The purpose of the present study is to investigate the risk assessment practices of a multidisciplinary mental health service. Findings indicate that mental health professionals draw on both managerial and therapeutic approaches to risk management, integrating these approaches into their clinical practice. Rather than being dominated by managerial concerns regarding risk, the participants demonstrate professional autonomy and concern for the needs of their clients.


PLCE1 mRNA and protein expression and survival of patients with esophageal squamous cell carcinoma and gastric adenocarcinoma.
Germline genetic variants in PLCE1 (10q23) have demonstrated consistent associations with risk of esophageal squamous cell carcinoma (ESCC) and gastric cancer among Chinese. We evaluated PLCE1 mRNA and protein expression in paired tumor-normal tissues, and their relationship with survival. PLCE1 mRNA was profiled using three probes in the Affymetrix GeneChip U133 for paired tumor-normal tissues of ESCC (n = 132), gastric cardia adenocarcinoma (GCA, n = 62), and gastric noncardia adenocarcinoma (GNCA, n = 72). We used immunohistochemistry to detect PLCE1 protein on slides from tissue microarrays in paired tumor-normal tissues of ESCC (n = 303), and tumors of GCA (n = 298) and GNCA (n = 124). Compared with normal tissues, PLCE1 mRNA expression was significantly reduced in ESCC tumors (P = 0.03, probe_205112_at), as well as in GCA and GNCA tumors (P < 0.0001, each probe). Protein expression was nonsignificantly reduced in ESCC tumors (P = 0.51). Increased tumor-normal mRNA fold change (probe_205112_at) was associated with longer survival in ESCC (9.6 months for highest vs. lowest quartile; Ptrend = 0.02). Increased mRNA tumor-normal fold change (probe_205111_at) was associated with longer survival for GCA (10.7 months for highest quartile; Ptrend = 0.04), but not for GNCA cases (P = 0.72). Similar to mRNA, elevated tumor-normal fold change for protein in ESCC was also associated with improved survival (8.1 months for highest quartile; Ptrend = 0.04). Dysregulated PLCE1 mRNA expression was observed for both ESCC (one probe only) and GCA tumors, and the altered PLCE1 expression seems to be associated with cancer prognosis. A potential role for PLCE1 in the early detection and/or therapy of ESCC and GCA warrants further investigation.


Overview of the Mars Pathfinder mission and assessment of landing site predictions.
Chemical analyses returned by Mars Pathfinder indicate that some rocks may be high in silica, implying differentiated parent materials. Rounded pebbles and cobbles and a possible conglomerate suggest fluvial processes that imply liquid water in equilibrium with the atmosphere and thus a warmer and wetter past. The moment of inertia indicates a central metallic core of 1300 to 2000 kilometers in radius. Composite airborne dust particles appear magnetized by freeze-dried maghemite stain or cement that may have been leached from crustal materials by an active hydrologic cycle. Remote-sensing data at a scale of generally greater than approximately 1 kilometer and an Earth analog correctly predicted a rocky plain safe for landing and roving with a variety of rocks deposited by catastrophic floods that are relatively dust-free.


Bilateral traumatic dislocation without fracture of the lumbosacral junction: case report and review of the literature.
Case report. The diagnosis and surgical management of a patient with a traumatic bilateral dislocation of the lumbosacral junction (L5-S1) without facet or pars interarticularis fracture is presented with a thorough review of the existing literature. Lumbar fracture-dislocations have been widely reported. However, only five cases of lumbosacral junction dislocation without a fracture have been previously reported. A 23-year-old patient was involved in a high-energy occupational injury and presented with complaints of back pain and inability to ambulate. Neurological assessment confirmed adequate motor strength (4+/5 bilaterally), normal perianal and lower extremity sensation, and urinary retention (postvoid residual: 1000 mL). Imaging studies revealed bilateral L5-S1 facet dislocation (bilateral jumped facets) without articulating processes or pars interarticularis fractures. Three-column ligamentous injury was confirmed on magnetic resonance imaging with complete tear of the ligamentum flavum, anterior and posterior longitudinal ligaments, interspinous and supraspinous ligaments, and avulsion of the L5 spinous process. The patient underwent bilateral facetectomies, diskectomy, laminectomies, and reduction of slippage with interbody and posterolateral transpedicular instrumented fusion. At 1-year follow-up, the patient reported mild back pain well controlled with naproxen. He continued to report good improvement in his daily function. A careful clinical examination and imaging assessment must be done for appropriate diagnosis and treatment of this rare type of injury. Reduction in the face of intact articulating processes and pars interarticularis is challenging because of acting heavy forces on the lumbosacral joint. Facetectomies, nerve root decompression, and circumferential instrumented fusion are ways to decompress the neural elements, restore alignment, and maintain segmental stability.


Method for combinatorial screening of moisture vapor transmission rate.
A high-throughput method for screening the moisture vapor transmission rate of barrier films was developed. This moisture high-throughput screening (MHTS) technique is based upon a Nafion-crystal violet (CVN) sensor that changes color from yellow to green upon absorption of water. Using an appropriate set of known standards, the slope of absorbance (at 630 nm) as a function of time can be converted into moisture vapor transmission rate (MVTR) values that agree with those obtained using ASTM F1290. High-throughput screening was demonstrated by depositing 20 emulsion-based poly(vinylidene chloride) films, using a 48-well template, of varying thicknesses onto the CVN sensor film and aging at 40 degrees C and 90% relative humidity for 72 h. MVTR values were accurately determined to a level of 0.9 g/m(2).day, at which point side-diffusion of moisture between the barrier and sensor films prevented observation of lower values. Larger sample size and edge-sealing are two proposed methods for improving the sensitivity of MHTS.


Angiolymphoid hyperplasia with eosinophilia of the external ear canal.
Angioblastic lymphoid hyperplasia with eosinophilia, or Kimura's disease, is a clinically and histopathologically recognized entity that is characterized by cutaneous nodules, proliferating blood vessels with atypical histiocyte-like endothelial cells, and numerous eosinophils. It has been treated with steroids and by surgical excision, irradiation, cryotherapy, and electrodesiccation. Persistent residual disease and local recurrence are frequent. We review the literature and report two cases that involve the ear. We present the histopathologic and clinical results of laser removal of a conchal and external canal lesion.


Peptide YY release after intraduodenal, intraileal, and intracolonic administration of nutrients in rats.
Peptide YY (PYY) release was studied by measuring radioimmunoassayable PYY in the arterial plasma of anaesthetized rats receiving into the duodenum, ileum or colon either a complete semi-liquid meal (3ml, 21kJ) or elemental nutrients as isocaloric or isoosmolar solutions. PYY release induced by the intraduodenal meal peaked at 60min and lasted more than 120min. The integrated response of PYY over 120min was larger when the meal was administered into the duodenum than into the ileum. The undigested meal induced no release of PYY over a 120-min period when administered into the colon. When injected into the duodenum in isocaloric amounts to the meal, glucose and amino acids led to the release of as much PYY as did the meal, whereas oleic acid led to the release of less PYY. Part of these responses were due to osmolarity, since administration of intraduodenal hyperosmolar saline led to the release of about half as much PYY as did hyperosmolar glucose. In moderate amounts, and injected as a solution isoosmolar to plasma, oleic acid was a major PYY releaser; the amounts released were at least two times larger when oleic acid was administered into the duodenum than into the ileum and colon. Isoosmolar glucose and amino acids led to the release of no PYY when injected into the duodenum, but were nearly as active as oleic acid in the colon. Short-chain fatty acids induced the release of PYY when injected into the colon, but not into the ileum. Hexamethonium suppressed PYY release induced by the intraduodenal meal, but did not change PYY release induced by glucose or oleic acid in the colon. Urethane anaesthesia did not reduce PYY release induced by the intraduodenal meal. These results suggest that two mechanisms at least contribute to PYY release in the rat. An indirect, neural mechanism, involving nicotinic synapses, is prominent in the proximal small intestine; the stimulation is transmitted to ileal and colonic L-cells by undetermined pathways, but contact of nutrients with L-cells is not needed. Another mechanism, probably direct and quantitatively smaller, occurs in the distal intestine when nutrients come into contact with the mucosa containing L-cells. Glucose, fatty acids and amino acids stimulate differentially the proximal and distal mechanisms.


Better understanding of food and human microbiomes through collaborative research on Inuit fermented foods.
Reports on fermented, animal-sourced foods made by Inuit around the circumpolar North have lacked consideration for their unique microbiota and the geo-socio-cultural contexts in which they are made, often resulting in reinforced negative stereotypes. Deficit-based approaches to studying Inuit fermented foods overlook the fact that they have long been considered healthy and integral to Inuit diets. Inuit have deep knowledge on the harvesting, preparation, sharing, and consumption of fermented foods that research efforts must learn from and acknowledge. Our preliminary research into Inuit animal-sourced fermented foods expands current knowledge about the microorganisms needed to make them, and points to a potential to understand how these and other fermented foods impact the human gut microbiome. We provide recommendations for microbiological research on Inuit fermented foods that centers Inuit knowledge within the specific geographic, social, and cultural contexts in which these foods are made.


TMEM74 promotes tumor cell survival by inducing autophagy via interactions with ATG16L1 and ATG9A.
Autophagy is a highly inducible system of intracellular degradation that occurs in lysosomes or vacuoles. Transmembrane 74 (TMEM74) has been shown to induce autophagy. However, the mechanism by which TMEM74 stimulates autophagy and the impacts of TMEM74-induced autophagy on tumor cell survival remain unclear. In this study, TMEM74 was shown to increase the autophagic flux process in different tumor cell lines. Further investigations revealed that TMEM74 interacts with ATG16L1 and ATG9A. Moreover, distinctive from the common autophagy models, it is found that TMEM74-related autophagy is independent of BECN1/PI3KC3 complex and ULK1, and TMEM74 may initiate and promote autophagy directly via interactions with ATG16L1 and ATG9A responsible for the nucleation and elongation respectively. Considering the ultimate outcome of TMEM74-induced autophagy in tumor cells, TMEM74-triggered autophagy induces a pro-survival effect on tumor cells, particularly cells under metabolic stress, consistent with alteration of a series of signal pathways. Intriguingly, TMEM74 itself can be downregulated through the autophagic process, which indicates that a potential self-regulatory loop exists so as to maintain an appropriate level of autophagy, avoiding excessive autophagy to commit tumor cells to death. According to the clinical database analysis, the high expression of TMEM74 significantly shortens the surviving periods of patients in several specific cancers indicating that TMEM74 itself can be treated as an effective potential target with clinical values to prolong surviving periods of cancer patients in the future. In conclusion, our study reveals a new mechanism by which autophagy is stimulated by a novel positive modulator through a unique pathway and demonstrates a novel connection between autophagy and cell survival, which undoubtedly serves to broaden our understanding of autophagy.


Differential expression of adrenomedullin and resistin in 3T3-L1 adipocytes treated with tumor necrosis factor-alpha.
It has recently been shown that deficiency of adrenomedullin (AM), a potent vasodilator peptide, leads to insulin resistance. We studied expression of AM in NIH 3T3-L1 adipocytes and compared it with expression of resistin, an adipocyte-derived peptide hormone that is proposed to cause insulin resistance. Moreover, we studied the effects of tumor necrosis factor-alpha (TNF-alpha), a known mediator of insulin resistance, on the expression of AM and resistin in 3T3-L1 adipocytes. 3T3-L1 cells were induced to differentiate to adipocytes by insulin, dexamethasone and 3-isobutyl-1-methylxanthine. Expression of AM mRNA and resistin mRNA was examined by Northern blot analysis. Immunoreactive AM in the medium was measured by RIA. AM mRNA was expressed in preadipocytes, but barely detectable in adipocytes. Immunoreactive AM was detected in the medium of both preadipocytes and adipocytes, with about 2.5 times higher levels found in preadipocytes. In contrast, resistin mRNA was expressed in adipocytes, whereas it was not detected in preadipocytes. Treatment with TNF-alpha increased AM expression in both adipocytes and preadipocytes, whereas it decreased resistin mRNA levels in adipocytes. The present study has shown that AM expression was down-regulated and resistin expression was up-regulated during adipocyte differentiation of 3T3-L1 cells. TNF-alpha acted as a potent negative regulator of resistin expression and a potent positive regulator of AM expression in adipocytes, raising the possibility that in addition to its known actions in causing insulin resistance, TNF-alpha may also have actions against insulin resistance through AM and resistin.


[Effects of adult feeding on the reproduction and longevity of Noctuidae, Crambidae, Tortricidae and Elachistidae species].
This research evaluates the effect of the adult diet on the reproduction of Anticarsia gemmatalis Hübner, Heliothis virescens (Fabr.), Spodoptera frugiperda (J. E. Smith) (Noctuidae), Diatraea saccharalis (Fabr.) (Crambidae), Gymnandrosoma aurantianum Lima (Tortricidae) and Stenoma catenifer Walsingham (Elachistidae). Adults of all species were fed either water or a 10% honey solution. The egg viability for the 1st and 2nd egg masses, adult fecundity, longevity, number of mating and the ovigeny index (OI) (degree of ovarian maturation) were evaluated. Fecundity of A. gemmatalis and H. virescens was drastically reduced when females were fed only on water. Egg viability from both 1st and 2nd egg masses was variable between treatments. Females of A. gemmatalis, H. virescens and S. frugiperda, and males of some species had a reduced longevity when fed only on water. The number of matings was higher for A. gemmatalis and D. saccharalis when fed on water only. The OI was < 1.0 for all species evaluated indicating that all females may develop new oocytes as they age. Based on the OI and the reduced fecundity of A. gemmatalis and H. virescens, one observes that adult feeding is important for the reproduction of both species, and the IO is not a good parameter to indicate such condition. Spodoptera frugiperda, G. aurantianum, D. saccharalis and S. catenifer do not require any source of carbohydrates as adults to sustain their reproduction.


Establishing the safety and efficacy of an opioid titration protocol.
The primary goal of this single-group study was to determine the safety of a standard opioid titration order sheet to manage pain in ambulatory cancer patients. Secondary goals were to examine opioid toxicity and efficacy of this pain protocol. Twenty-seven patients who required fixed-dose opioids and who had uncontrolled pain were enrolled. All patients had their initial opioid dose titrated by the study physician using the opioid titration order sheet. Data were obtained by the study nurse during a weekly telephone interview and used to determine if pain was controlled. After initial titration, a trained study nurse titrated opioid doses based upon the standing order sheet. At each contact, patients were assessed for adverse effects, pain intensity, and analgesics used. Patients who completed the four-week trial (n = 17) did not differ from patients who did not complete the trial. No adverse effects were observed in 39 opioid titrations completed by the study nurse. Opioid toxicities, worst pain, usual pain, and pain-related distress declined from baseline to week four. Patients who were adherent to their prescribed medications reported significantly lower pain intensity and distress (ps < or = 0.06). The opioid titration order sheet, used by a trained nurse, is safe to use in ambulatory cancer patients who have moderate to severe pain. Common opioid toxicities were reduced. The protocol also demonstrated initial efficacy in improving worst and usual pain and pain-related distress. Further research to establish efficacy of the protocol is recommended.


Submissive Behaviour, Depression, and Suicide Probability in Male Arrestees and Convicts.
The aim of this study was to determine the relationship of suicide probability with submissive behaviors and the levels of depression in male arrestees and convicts staying in penal institutions. The study consisted of 326 male participants from five different prisons. A personal information form was used to collect the socio-demographic data, The Suicide Probability Scale (SPS), Beck Depression Inventory (BDI) and the Submissive Behaviour Scala (SBS) were used to determine the related psychological characteristics. The results showed that depression was determined in 69% of the inmates (convicts and arrestees), while the suicide probability rate was found to be in the proportion of 88% which is higher than in the general population. Regarding the examination in terms of crime types, it was found that the suicide ideation rate of sex offenders or sex offender arrestees (x=18.33; ss=7.28) and the hostility rate of bulglary offenders (x=16.63; ss=4.75) were much higher than that of the other types of offenders. According to the findings of the Hierarchical Regression Analysis conducted in order to define the variables predicting the subscale rates of SPS, while previous suicide attempt(s) and depression predict hopelessness rate; self-attempted suicide, witnessing suicide attempts, self-harm and depression predict suicide ideation rate. Furthermore, education status and depression symptoms predict negative self-evaluation rate, and lastly education level, witnessing suicide attempts, self-harm and depression symptoms predict hostility subscale rate. Factors such as social isolation, mislearning, etc. were considered to cause increased feelings of hopelessness, suicide ideation, negative sense of self and feelings of hostility in convicts and arrestees staying indoors.


Rectal cancer patients from rural areas in northern Sweden report more pain and problems with stoma care than those from urban areas.
Having a stoma after bowel surgery is associated with inferior quality of life (QoL). The county of Västerbotten in Sweden is a large and sparsely populated area. Competence regarding stoma-related problems is restricted to hospital-based stoma nurses and surgeons. Patients living in rural areas instead largely rely on their general practitioner. The purpose of the study was to investigate the impact of distance to nearest hospital on the QoL of rectal cancer patients who receive a stoma at index surgery. A cross-sectional study performed in Västerbotten county, Sweden. Validated questionnaires assessing QoL (EORTC QLQ C-30 and CR-29) were sent to all rectal cancer patients diagnosed in 2007-2014 who received a stoma at index surgery. Socioeconomic variables were retrieved from Statistics Sweden. Distance from home to the nearest hospital was determined using Google Maps™. The effect of distance was assessed using two separate models, the first based on distance to the nearest hospital and the second based on access to a stoma care nurse. Within the first model all patients living in rural areas constituted the study group while all patients living in non-rural areas constituted the control group. Within the second model all patients with no access to stoma care nurse constituted the study group while those with such access constituted the control group. The response rate was 69%. In the first model the rectal cancer patients living further away from the nearest hospital reported significantly more pain and sore skin (p=0.032 and p=0.003, respectively). When considering patients who still had a stoma, those living further away also reported more stoma care problems (p=0.004) and a poorer global QoL (p=0.038). In the second model, access or not to a stoma care nurse had no impact on stoma care problems or QoL. Rectal cancer patients receiving a stoma at index surgery and who came from rural areas reported more pain than those living closer to the nearest hospital. The group of rural patients who still had a stoma also reported more stoma care problems and a poorer quality of life. To help these patients, general practitioners are encouraged to arrange an extra follow-up visit focusing on the individual patient´s problems.


Foreign material in postoperative adhesions.
The authors determined the prevalence of foreign body granulomas in intra-abdominal adhesions in patients with a history of abdominal surgery. In a cross-sectional, multicenter, multinational study, adult patients with a history of one or more previous abdominal operations and scheduled for laparotomy between 1991 and 1993 were examined during surgery. Patients in whom adhesions were present were selected for study. Quantity, distribution, and quality of adhesions were scored, and adhesion samples were taken for histologic examination. In 448 studied patients, the adhesions were most frequently attached to the omentum (68%) and the small bowel (67%). The amount of adhesions was significantly smaller in patients with a history of only one minor operation or one major operation, compared with those with multiple laparotomies (p < 0.001). Significantly more adhesions were found in patients with a history of adhesions at previous laparotomy (p < 0.001), with presence of abdominal abscess, hematoma, and intestinal leakage as complications after former surgery (p = 0.01, p = 0.002, and p < 0.001, respectively), and with a history of an unoperated inflammatory process (p = 0.04). Granulomas were found in 26% of all patients. Suture granulomas were found in 25% of the patients. Starch granulomas were present in 5% of the operated patients whose surgeons wore starch-containing gloves. When suture granulomas were present, the median interval between the present and the most recent previous laparotomy was 13 months. When suture granulomas were absent, this interval was significantly longer--i.e., 30 months (p = 0.002). The percentage of patients with suture granulomas decreased gradually from 37% if the previous laparotomy had occurred up to 6 months before the present operation, to 18% if the previous laparotomy had occurred more than 2 years ago (p < 0.001). The number of adhesions found at laparotomy was significantly larger in patients with a history of multiple laparotomies, unoperated intra-abdominal inflammatory disease, and previous postoperative intra-abdominal complications, and when adhesions were already present at previous laparotomy. In recent adhesions, suture granulomas occurred in a large percentage. This suggests that the intra-abdominal presence of foreign material is an important cause of adhesion formation. Therefore intra-abdominal contamination with foreign material should be minimized.


[A comparative analysis of the course of odontogenic phlegmons of the face and neck area in patients from Yakutsk and Moscow].
A total of 126 patients with odontogenic inflammatory diseases were examined, 54 of these in Moscow and 72 in Yakutsk. The clinical and immunological parameters were assessed on days 2 and 6 after similar operations. In residents of Yakutsk the inflammatory process was associated with a more expressed intoxication and coursed 1.5 to 2 days longer than in Muscovites; moreover, the residents of Yakutsk developed higher leukocytosis and a drop of T-lymphocyte level with the predominance of T-helpers. Hence, odontogenic inflammations take mainly a hyperergic course in Yakutsk and a normergic one in Moscow.


Detection of damage on single- or double-stranded DNA in a population exposed to arsenic in drinking water.
Different studies have suggested an association between arsenic (As) exposure and damage to single-stranded DNA by reactive oxygen species derived from the biotransformation of arsenic. The single strand damages are converted to double strand damage upon interaction with ultraviolet radiation. Analysis of genomic integrity is important for assessing the genotoxicity caused by environmental pollutants. In this study, we compared the concentration of As in drinking water, nutritional status, lifestyle variables, and the level of genotoxicity in an exposed population and a control group. Arsenic content of water was determined using a portable Arsenator® kit. DNA fragmentation was determined using the two-tailed comet assay. Our results show that the exposed population had low nutritional consumption compared to the control group (P < 0.05). Furthermore, the water consumed by the exposed group had As concentration of 14.3 ± 8.4 mg/L, whereas the As level in the water consumed by the control group was 7.7 ± 3.5 mg/L. Analysis shows that the frequency of double strand break (DSB) fragmentation was higher in the population exposed to higher levels of As compared to that of the control group. These results suggest a possible association between the concentration of As in drinking water and lifestyle variables, with increasing fragmentation of DSBs in the exposed population.


Lack of involvement of capsaicin-sensitive primary afferents in nerve-ligation injury induced tactile allodynia in rats.
Tactile allodynia and thermal hyperalgesia, two robust signs of neuropathic pain associated with experimental nerve injury, have been hypothesized to be mechanistically distinguished based on (a) fiber types which may be involved in the afferent input, (b) participation of spinal and supraspinal circuitry in these responses, and (c) sensitivity of these endpoints to pharmacological agents. Here, the possibility that nerve-injury induced tactile allodynia and thermal hyperalgesia may be mediated via different afferent fiber input was tested by evaluating these responses in sham-operated or nerve-injured (L5/L6) rats before or after a single systemic injection of resiniferatoxin (RTX), an ultrapotent analogue of the C-fiber specific neurotoxin, capsaicin. Tactile allodynia, and three measures of thermal nociception, tail-flick, paw-flick and hot-plate responses, were determined before and at various intervals for at least 40 days after RTX injection. Nerve-injured, but not sham-operated, rats showed a long-lasting tactile allodynia and thermal hyperalgesia (paw-flick) within 2-3 days after surgery; responses to other noxious thermal stimuli (i.e., tail-flick and hot-plate tests) did not distinguish the two groups at the stimulus intensities employed. RTX treatment resulted in a significant and long-lasting (i.e. essentially irreversible) decrease in sensitivity to thermal noxious stimuli in both sham-operated and nerve-injured rats; thermal hyperalgesia was abolished and antinociception produced by RTX. In contrast, RTX treatment did not affect the tactile allodynia seen in the same nerve-injured rats. These data support the concept that thermal hyperalgesia seen after nerve ligation, as well as noxious thermal stimuli, are likely to be mediated by capsaicin-sensitive C-fiber afferents. In contrast, nerve-injury related tactile allodynia is insensitive to RTX treatment which clearly desensitizes C-fibers and, therefore such responses are not likely to be mediated through C-fiber afferents. The hypothesis that tactile allodynia may be due to inputs from large (i.e. A beta) afferents offers a mechanistic basis for the observed insensitivity of this endpoint to intrathecal morphine in this nerve-injury model. Further, these data suggest that clinical treatment of neuropathic pains with C-fiber specific agents such as capsaicin are unlikely to offer significant therapeutic benefit against mechanical allodynia.


Ozone responses to reduced precursor emissions: A modeling analysis on how attainable goals can improve air quality in the Mexico City Metropolitan Area.
High tropospheric ozone (O3) concentrations prevent the improvement of the air quality in the Mexico City Metropolitan Area (MCMA). Although the problem has improved considerably since the 1990s, a rebound in O3 levels in recent years has raised concerns about the deteriorating air quality. The nonlinear relationship between O3 formation and the emissions of its main precursors, i.e., volatile organic compounds (VOCs) and nitrogen oxides (NOx), is a challenge when measures are enacted for effective mitigation of the O3 problem. This study evaluated the reduction in precursors, VOCs and NOx, using an up-to-date regional air quality model (HERMES-Mex-WRF-CMAQ). For evaluating realizable scenarios, the decline in VOC achieved in Japan after policy implementation was the targeted VOC reduction (40 % from area sources), and the NOx reduction observed in the MCMA during the COVID-19 pandemic was the targeted NOx reduction (40 % from mobile sources). The analysis evaluated the O3 responses to changes in a single precursor and a combination of both during a period of high O3 concentrations (April 2019). The results showed that 40 % reduction in VOC emissions would decrease the O3 8-h maximum concentrations by 16 %. However, 40 % reduction in NOx emissions would increase O3 by >15 %. The simultaneous reduction of both precursors did not significantly affect O3 levels. The diagnosis of ozone sensitivity using the H2O2/HNO3 ratios reinforced the simulation findings, indicating that VOC emissions limited ozone formation in most MCMA areas. As the simulated scenarios were based on factual case studies, our research offers insights into the realistic aims of MCMA policies to reduce O3 levels.


Getting real performance out of pay-for-performance.
Most private and public health insurers are implementing pay-for-performance (P4P) programs in an effort to improve the quality of medical care. This article offers a paradigm for evaluating how P4P programs should be structured and how effective they are likely to be. This article assesses the current comprehensiveness of evidence-based medicine by estimating the percentage of outpatient medical spending for eighteen medical processes recommended by the Institute of Medicine. Three conditions must be in place for outcomes-based P4P programs to improve the quality of care: (1) health insurers must not fully understand what medical processes improve health (i.e., the health production function); (2) providers must know more about the health production function than insurers do; and (3) health insurers must be able to measure a patient's risk-adjusted health. Only two of these conditions currently exist. Payers appear to have incomplete knowledge of the health production function, and providers appear to know more about the health production function than payers do, but accurate methods of adjusting the risk of a patient's health status are still being developed. This article concludes that in three general situations, P4P will have a different impact on quality and costs and so should be structured differently. When information about patients' health and the health production function is incomplete, as is currently the case, P4P payments should be kept small, should be based on outcomes rather than processes, and should target physicians' practices and health systems. As information improves, P4P incentive payments could be increased, and P4P may become more powerful. Ironically, once information becomes complete, P4P can be replaced entirely by "optimal fee-for-service."


Post-infarct morphine treatment reduces apoptosis and myofibroblast density in a rat model of cardiac ischemia-reperfusion.
Following myocardial ischemia, the cardiac tissue undergoes both, physiological and pathological changes to compensate the initial loss of function. Long-term continuous adjustments often take a drastic picture indicated by deteriorated ventricular function. Morphine is commonly used for rescuing patients suffering a heart attack. Recent results from our laboratory showed the anti-remodeling potential of morphine. Here, we explored the effect of morphine treatment on gelatinolytic activity, apoptosis and myofibroblast density. The male Sprague - Dawley rats underwent ischemia via ligation of left anterior descending coronary artery and received morphine (3 mg/kg; i.p.) for five consecutive days. Seven days post-MI, morphine led to significant reduction in MMP - 2 activity, apoptotic cell death and fibroblast density. Morphine also reduced MI-induced rise in serum pro-oxidant antioxidant balance and nitrite levels on day 28th following the surgery. These results provide mechanistic insight for morphine - induced anti-remodeling effects.


Oral contraceptives and other risk factors for gallbladder disease.
Prior studies of the association between oral contraceptives (OCs) and gallbladder disease (GBD) have yielded conflicting results. To clarify this association, a retrospective (historical) cohort study was performed on a very large data base including 1980 and 1981 Medicaid billing data from the states of Michigan and Minnesota in which 138,943 users of OCs were compared with 341,478 nonusers. The crude relative risk (RR) and 95% confidence interval (CI) for symptomatic GBD resulting in medical care was 1.14 (CI 1.09 to 1.20), with a clear dose-response (P less than 0.001). Age markedly modified the effect of OCs on GBD. The RR (CI) decreased from 3.1 (2.7 to 3.6) in women 15 to 19 years old to 1.2 (0.9 to 1.5) in women 40 to 44 years old, providing an explanation for previously conflicting reports. The effects of a number of other risk factors on GBD, some which have been controversial, were also confirmed. Adjustment for these did not change the results. In conclusion, OCs are risk factors for GBD, although the risk is of sufficient magnitude to be of potential clinical importance only in young women.


Sodium renders endothelial cells sticky for red blood cells.
Negative charges in the glycocalyx of red blood cells (RBC) and vascular endothelial cells (EC) facilitate frictionless blood flow through blood vessels. Na(+) selectively shields these charges controlling surface electronegativity. The question was addressed whether the ambient Na(+) concentration controls RBC-EC interaction. Using atomic force microscopy (AFM) adhesion forces between RBC and endothelial glycocalyx were quantified. A single RBC, mounted on an AFM cantilever, was brought in physical contact with the endothelial surface and then pulled off. Adhesion forces were quantified (i) after enzymatic removal of negative charges in the glycocalyx, (ii) under different ambient Na(+) and (iii) after applying the intracellular aldosterone receptor antagonist spironolactone. Removal of negative surface charges increases RBC-EC interaction forces. A stepwise increase of ambient Na(+) from 133 to 140 mM does not affect them. However, beyond 140 mM Na(+) adhesion forces increase sharply (10% increase of adhesion force per 1 mM increase of Na(+)). Spironolactone prevents this response. It is concluded that negative charges reduce adhesion between RBC and EC. Ambient Na(+) concentration determines the availability of free negative charges. Na(+) concentrations in the low physiological range (below 140 mM) allow sufficient amounts of vacant negative charges so that adhesion of RBC to the endothelial surface is small. In contrast, Na(+) in the high physiological range (beyond 140 mM) saturates the remaining negative surface charges thus increasing adhesion. Aldosterone receptor blockade by spironolactone prevents Na(+) induced RBC adhesion to the endothelial glycocalyx. Extrapolation of in vitro experiments to in vivo conditions leads to the hypothesis that high sodium intake is likely to increase the incidence of thrombotic events.


Differences in markers of cardiovascular disease between professional football players of West-Asian and Black African descent.
To examine the cardiovascular risk factors of professional football players of West-Asian and Black African descent competing in the 2010/11 Qatar Stars League. Ten out of twelve professional football clubs attended pre-participation screening. 100 West-Asian males from seven Gulf States and six Middle-Eastern countries and 90 Black males from seven African countries. All players were screened using the FIFA pre-competition medical assessment, incorporating a physical examination, resting 12-Lead ECG, echocardiogram, with determination of total cholesterol, high and low density lipoprotein (HDL/LDL) and triglycerides. West-Asian football players had a higher prevalence of a family history (FH) of coronary heart disease (CHD) (25% vs. 12%, p = 0.025) compared to Black African players predominantly due to CHD in their fathers (14% vs. 6%, p<0.05). West-Asian players had higher total cholesterol levels (4.4 vs. 4.2 mmol/L, p = 0.025) and lower HDL levels (1.3 vs. 1.4 mmol/L, p = 0.004) than Black African players; remaining significant after adjusting for a FH of CHD. Positively, all lipid levels were clinically acceptable for both ethnicities. Finally, one in eight West-Asian and one in eleven Black African football players were regular smokers. The prevalence of cardiovascular disease in West-Asia is increasing. This study observed clinically acceptable blood lipid profiles for both West-Asian and Black African football players. However, West-Asian players had a greater number of markers for CVD than their Black African counterparts despite being matched for physical activity levels. Targeted education with regards to diet, lifestyle and tobacco use is required for both ethnicities.


Further studies on the absorption of actinide elements from the gastrointestinal tract of neonatal animals.
Plutonium retention was measured after intragastric administration to neonatal rats, dogs and swine. At 1 week after administration, substantially more of the actinide remained in swine and dogs than in rats. The quantity of 238Pu absorbed by piglets was markedly influenced by such factors as compound solubility, mass of plutonium administered, oxidation state of the actinide, and age of the animal at gavage. Cortisone treatment reduced absorption, but was less effective in piglets than in neonatal rats. Measurements of 238Pu transport from ligated segments of the neonatal swine intestine indicated highest absorption from the duodenum, where the actinide was shown, autoradiographically, to be deposited in the epithelial region; in the ileum, deposition was predominantly in the lacteal region. Absorption of actinides by neonatal swine decreased in the order of 233U greater than 238Pu greater than 237Np greater than 244Cm greater than 241Am. Measurements at 1 yr after gavage showed a much higher retention by swine than by rats.


[DNA repair in mammalian nerve cells. I. DNA synthesis in the neocortex of rats induced by gamma irradiation].
A study was made of the DNA synthesis in cerebral cortex of rats, aged 14 and 60 days, after gamma-irradiation in vivo in a dose of 7 Gy, the 3H-thymidine incorporation into DNA being determined.137 Cs-radiation induces additional DNA synthesis in the neocortex tissue and in neurons. In the cortex of 14 day-old rats, the induced DNA synthesis stops 2 hours after irradiation, whereas in the cortex of 60 day-old rats and in neurons of rats of both the age groups DNA synthesis is proceeding for 3-3.5 hours. Specificity of DNA reparation processes in non-dividing cells is discussed.


Bovine tuberculosis in Ethiopian wildlife.
Bovine tuberculosis (BTB) is endemic in Ethiopian cattle. However, the status of the disease in wildlife populations that often share habitat with livestock is unknown. We screened for BTB in wildlife in five regions in Ethiopia. Blood and tissue samples from 133 mammals of 28 species were collected from 2006 to 2008. We used a rapid serology test (RT) based on lateral flow technology, and performed culture of lymph node specimens inoculated onto Lowenstein-Jensen and Middlebrook 7H11 media. Acid-fast colonies were further analyzed by molecular typing. Sera from 20 of 87 animals (23%) were positive for BTB by RT; acid-fast bacilli were cultured from 29 of 89 animals (32.5%). None of the positive cultures yielded mycobacteria from the Mycobacterium tuberculosis complex but many environmental mycobacteria were isolated. Among these, Mycobacterium terrae was the most common. We demonstrated a high prevalence of environmental mycobacteria in wildlife, the role of which is unknown. Flagship rare endemic species such as the mountain nyala (Tragelaphus buxtoni) and the Ethiopian wolf (Canis simensis) may be at risk for BTB. We also assessed the utility of RT for field purposes.


Cognitive functioning in prodromal psychosis: a meta-analysis.
A substantial proportion of people at clinical high risk (HR) of psychosis will develop a psychotic disorder over time. Cognitive deficits may predate the onset of psychosis and may be useful as markers of increased vulnerability to illness. To quantitatively examine the cognitive functioning in subjects at HR in the literature to date. Electronic databases were searched until January 2011. All studies reporting cognitive performance in HR subjects were retrieved. Nineteen studies met the inclusion criteria, comprising a total of 1188 HR subjects and 1029 controls. Neurocognitive functioning and social cognition as well as demographic, clinical, and methodological variables were extracted from each publication or obtained directly from its authors. Subjects at HR were impaired relative to controls on tests of general intelligence, executive function, verbal and visual memory, verbal fluency, attention and working memory, and social cognition. Processing speed domain was also affected, although the difference was not statistically significant. Later transition to psychosis was associated with even more marked deficits in the verbal fluency and memory domains. The studies included reported relatively homogeneous findings. There was no publication bias and a sensitivity analysis confirmed the robustness of the core results. The HR state for psychosis is associated with significant and widespread impairments in neurocognitive functioning and social cognition. Subsequent transition to psychosis is particularly associated with deficits in verbal fluency and memory functioning.


Efficacy, safety, and tolerability of antihypertensive therapy with aliskiren/amlodipine in clinical practice in Austria. The RALLY (Rasilamlo long lasting efficacy) study.
This observational study evaluated the efficacy and tolerability of 3-month aliskiren/amlodipine therapy under outpatient conditions. This Austria-wide observational study included 579 hypertensive patients (566 [98 %] who could be analyzed biometrically) under the care of 140 physicians. The average age of the patient collective was 64 ± 11 years and the mean duration of hypertension was 10 ± 7 years. Regarding 92 % of the study participants, an antihypertensive therapy already existed. Efficacy was assessed in accordance with the Austrian hypertension guidelines while tolerability was evaluated on the basis of adverse events. A descriptive physician judgment based on efficacy, tolerability, and compliance was available for 539 patients (95 %). Office blood pressure values were used for the evaluation. On average, the systolic and diastolic blood pressures were reduced from 161 ± 14 to 135 ± 10 mmHg and 93 ± 9 to 81 ± 6 mmHg, respectively. Blood pressure values of < 140/90 mmHg and < 130/80 mmHg were achieved in 56 and 7 % patients, respectively. A subgroup analysis of 242 patients (43 %) with diabetes mellitus and/or renal disease, as well as those with a high cardiovascular risk, demonstrated nearly identical results compared to the total population. Overall, 44 adverse events were documented in 41 patients, and physicians reported that 94 % of patients were compliant in a final survey on evaluation of therapy. The fixed-dose combination of aliskiren/amlodipine provided clinically relevant blood pressure reductions along with good tolerance and compliance. During the 3-month duration of observation under outpatient conditions, it was seen that aliskiren and amlodipine reduced the systolic and diastolic blood pressures on average by 26 and 13 mmHg, respectively.


Qualitative assessment of the role of public health education program on HIV transmission dynamics.
This paper presents a non-linear deterministic model for assessing the impact of public health education campaign on curtailing the spread of the human immunodeficiency virus (HIV) pandemic in a population. Rigorous qualitative analysis of the model reveals that it exhibits the phenomenon of backward bifurcation (BB), where a stable disease-free equilibrium coexists with a stable endemic equilibrium when a certain threshold quantity, known as the 'effective reproduction number' ('Reff), is less than unity. The epidemiological implication of BB is that a public health education campaign could fail to effectively control HIV even when the classical requirement of having the associated reproduction number less than unity is satisfied. Furthermore, an explicit threshold value is derived above which such an education campaign could lead to detrimental outcome (increase disease burden) and below which it would have positive population-level impact (reduce disease burden in the community). It is shown that the BB phenomenon is caused by imperfect efficacy of the public health education program. The model is used to assess the potential impact of some targeted public health education campaigns using data from numerous countries.


Pathogenesis of murine enterovirus myocarditis: virus dissemination and immune cell targets.
In order to identify organ and cellular targets of persistent enterovirus infection in vivo, immunocompetent mice (SWR/J, H-2q) were inoculated intraperitoneally with coxsackievirus B3 (CVB3). By use of in situ hybridization for the detection of enteroviral RNA, we show that CVB3 is capable of inducing a multiorgan disease. During acute infection, viral RNA was visualized at high levels in the heart muscle, pancreas, spleen, and lymph nodes and at comparably low levels in the central nervous system, thymus, lung, and liver. At later stages of the disease, the presence of enteroviral RNA was found to be restricted to the myocardium, spleen, and lymph nodes. To characterize infected lymphoid cells during the course of the disease, enteroviral RNA and cell-specific surface antigens were visualized simultaneously in situ in spleen tissue sections. In acute infection, the majority of infected spleen cells, which are located primarily at the periphery of lymph follicles, were found to express the CD45R/B220+ phenotype of pre-B and B cells. Whereas viral RNA was also detected in certain CD4+ helper T cells and Mac-1+ macrophages, no enteroviral genomes were identified in CD8+ cytotoxic/suppressor T cells. Later in disease, the localization of enteroviral RNA revealed a persistent type of infection of B cells within the germinal centers of secondary follicles. In addition, detection of the replicative viral minus-strand RNA intermediate provided evidence for virus replication in lymphoid cells of the spleen during the course of the disease. These data indicate that immune cells are important targets of CVB3 infection, providing a noncardiac reservoir for viral RNA during acute and persistent myocardial enterovirus infection.


Teaching laboratory neuroscience at bowdoin: the laboratory instructor perspective.
Bowdoin College is a small liberal arts college that offers a comprehensive Neuroscience major. The laboratory experience is an integral part of the major, and many students progress through three stages. A core course offers a survey of concepts and techniques. Four upper-level courses function to give students more intensive laboratory research experience in neurophysiology, molecular neurobiology, social behavior, and learning and memory. Finally, many majors choose to work in the individual research labs of the Neuroscience faculty. We, as laboratory instructors, are vital to the process, and are actively involved in all aspects of the lab-based courses. We provide student instruction in state of the art techniques in neuroscience research. By sharing laboratory teaching responsibilities with course professors, we help to prepare students for careers in laboratory neuroscience and also support and facilitate faculty research programs.


Genomic localization of the human gene for KCNA10, a cGMP-activated K channel.
Potassium (K) channels are important components of virtually all cells, and they play critical roles in many cellular functions. KCNA10 represents a new class of K channel specifically regulated by cGMP and postulated to mediate the effects of substances that increase intracellular cGMP. Since KCNA10 has the potential to be useful in candidate gene analysis of inherited diseases, the human gene for KCNA10 was characterized. Fluorescence in situ hybridization indicates that human KCNA10 maps to chromosome 1 at p13.1-->p22.1. Finer mapping of the gene was achieved by PCR of a set of CEPH YAC clones that spanned the region of interest. We found that YAC 818b9 contains human KCNA10. These data indicate human KCNA10 maps to 1p13.1 and resides within the genetic interval defined by microsatellite loci D1S2809 and D1S2726. That region of chromosome 1 contains another K channel gene, KCNA3.


Clopidogrel-induced qualitative changes in thrombus formation correlate with stent patency in injured pig cervical arteries.
Thienopyridines (ticlopidine or clopidogrel) alone or in combination with aspirin are now the reference antiplatelet therapy after stent implantation. To better understand the high efficacy and low risk of bleeding with these agents, we tested clopidogrel alone or with aspirin in an acute ex vivo flow chamber model and in a subacute in vivo arterial thrombosis model. Clopidogrel induced a dose-dependent increase in bleeding time (BT), inhibited ADP-induced platelet aggregation and in the flow chamber reduced thrombus size, and changed thrombus structure to broad-based structure composed of nondegranulated loosely attached platelets contrasting with the tight clumps of degranulated platelets seen without clopidogrel. The in vivo model involved angioplasty and stenting at the site of a preinduced arterial lesion and thrombosis in pig carotid arteries. Clopidogrel alone or with aspirin (but not aspirin alone) decreased the number of stented vessels occluded for more than 24 h and conversely reduced the number of occluding thrombus. At 96 h after stenting, 100% and 90% of the arteries were patent with clopidogrel/aspirin and clopidogrel alone, respectively (vs. 67% and 44% with aspirin and saline, respectively). Clopidogrel destabilizes thrombus without complete abolishment of platelet reactivity.


GPR105 ablation prevents inflammation and improves insulin sensitivity in mice with diet-induced obesity.
GPR105, a G protein-coupled receptor for UDP-glucose, is highly expressed in several human tissues and participates in the innate immune response. Because inflammation has been implicated as a key initial trigger for type 2 diabetes, we hypothesized that GPR105 (official gene name: P2RY14) might play a role in the initiation of inflammation and insulin resistance in obesity. To this end, we investigated glucose metabolism in GPR105 knockout (KO) and wild-type (WT) mice fed a high-fat diet (HFD). We also examined whether GPR105 regulates macrophage recruitment to liver or adipose tissues by in vivo monocyte tracking and in vitro chemotaxis experiments, followed by transplantation of bone marrow from either KO or WT donors to WT recipients. Our data show that genetic deletion of GPR105 confers protection against HFD-induced insulin resistance, with reduced macrophage infiltration and inflammation in liver, and increased insulin-stimulated Akt phosphorylation in liver, muscle, and adipose tissue. By tracking monocytes from either KO or WT donors, we found that fewer KO monocytes were recruited to the liver of WT recipients. Furthermore, we observed that uridine 5-diphosphoglucose enhanced the in vitro migration of bone marrow-derived macrophages from WT but not KO mice, and that plasma uridine 5-diphosphoglucose levels were significantly higher in obese versus lean mice. Finally, we confirmed that insulin sensitivity improved in HFD mice with a myeloid cell-specific deletion of GPR105. These studies indicate that GPR105 ablation mitigates HFD-induced insulin resistance by inhibiting macrophage recruitment and tissue inflammation. Hence GPR105 provides a novel link between innate immunity and metabolism.


Assay of cefotaxime by high-pressure-liquid chromatography.
A high-pressure-liquid chromatographic (HPLC) procedure for quantitative assay of cefotaxime (CT) and its major metabolite in serum of normal individuals, desacetyl cefotaxime (DACT), is described. It employs Lichrosorb RP-8, elution with phosphoric-acid-methanol and UV absorption at 310 nm. The method is optimized for cefotaxime and allows differentiation between the parent compound and the biotransformation product DACT. The lower assay sensitivity level of CT and DACT is 0.3 microgram/ml. Correlation between HPLC and microbiological assay with Escherichia coli or Proteus rettgeri of pooled serum with CT added is r = 0.99. The method is rapid; processing of one sample takes 17 min. Use of HPLC avoids the errors of microbiological assays which derived from the presence in patient sera of different ratios of CT and DACT. The apparent rate of serum elimination is linearly related to the sensitivity of the microbial assay indicator strain to DACT. There is synergistic antibacterial activity between CT and DACT regardless of relative minimum inhibitory concentrations of the agents.


Women's sexual health and contraceptive needs after a severe obstetric complication ("near-miss"): a cohort study in Burkina Faso.
Little is known about the reproductive health of women who survive obstetric complications in poor countries. Our aim was to determine how severe obstetric complications in Burkina Faso affect reproductive events in the first year postpartum. Data were collected from a prospective cohort of women who either experienced life threatening (near-miss) pregnancy-related complications or an uncomplicated childbirth, followed from the end of pregnancy to one year postpartum or post-abortum. Documented outcomes include menses resumption, sexual activity resumption, dyspareunia, uptake of contraceptives, unmet needs for contraception and women's reproductive intentions.Participants were recruited in seven hospitals between December 2004 and March 2005 in six towns in Burkina Faso. Reproductive events were associated with pregnancy outcome. The frequency of contraceptive use was low in all groups and the method used varied according to the presence or not of a live baby. The proportion with unmet need for contraception was high and varied according to the time since end of pregnancy. Desire for another pregnancy was highest among near-miss women with perinatal death or natural abortion. Women in the near-miss group with induced abortion, perinatal death and natural abortion had significantly higher odds of subsequent pregnancy. Unintended pregnancies were observed mainly in women in the near-miss group with live birth and the uncomplicated delivery group. Considering the potential deleterious impact (on health and socio-economic life) of new pregnancies in near-miss women, it is important to ensure family planning coverage includes those who survive a severe complication.


Effects of trimonthly progestin administration on the endometrium in elderly postmenopausal women who receive hormone replacement therapy: a pilot study.
The purpose of this study was to determine the effect of trimonthly progestin administration on the endometrium in elderly postmenopausal women who receive hormone replacement therapy. This was a prospective, randomized, double-blind, placebo-controlled study at a university teaching program. Twenty-five postmenopausal women who were >or=75 years old with an intact uterus were assigned randomly to receive conjugated equine estrogens (0.625 mg/d plus medroxyprogesterone acetate 5 mg/d for 13 days every 3 months (n = 13) or placebo (n = 12) for 9 months). At the end of the 9 months, patients in the hormone replacement therapy arm continued therapy for an additional 9 months. Statistical analysis was performed with the Student t test, the chi(2) test, and the Fisher exact test. Transvaginal sonography was performed at baseline and at 9 and 18 months. Endometrial biopsy was performed if the endometrial thickness was >4 mm or as clinically indicated at 18 months. Patients in the hormone replacement therapy group demonstrated a significant increase in endometrial thickness between baseline (3.9 + 0.8 mm) and 9 months (8.0 + 4.8 mm). There were no cases of endometrial hyperplasia at the 18-month endometrial biopsy. Trimonthly progestin administration in elderly postmenopausal women who receive hormone replacement therapy may be a reasonable alternative to the monthly administration of progestin in hormone replacement therapy.


Effect of Substrate Morphology on the Odd-Even Effect in Hydrophobicity of Self-Assembled Monolayers.
Surface roughness, often captured through root-mean-square roughness (Rrms), has been shown to impact the quality of self-assembled monolayers (SAMs) formed on coinage metals. Understanding the effect of roughness on hydrophobicity of SAMs, however, is complicated by the odd-even effect-a zigzag oscillation in contact angles with changes in molecular length. We recently showed that for surfaces with Rrms > 1 nm, the odd-even effect in hydrophobicity cannot be empirically observed. In this report, we compare wetting properties of SAMs on Ag and Au surfaces of different morphologies across the Rrms ∼ 1 nm limit. We prepared surfaces with comparable properties (grain sizes and Rrms) and assessed the wetting properties of resultant SAMs. Substrates with Rrms either below or above the odd-even limit were investigated. With smoother surfaces (lower Rrms), an inverted asymmetric odd-even zigzag oscillation in static contact angles (θs) was observed with change from Au to Ag. Asymmetry in odd-even oscillation in Au was attributed to a larger change in θs from odd to even number of carbons in the n-alkanethiol and vice versa for Ag. For rougher surfaces, no odd-even effect was observed; however, a gradual increase in the static contact angle was observed. Increase in the average grain sizes (>3 times larger) on rough surfaces did not lead to significant difference in the wetting properties, suggesting that surface roughness significantly dominated the nature of the SAMs. We therefore infer that the predicted roughness-dependent limit to the observation of the odd-even effect in wetting properties of n-alkanethiols cannot be overcome by creating surfaces with large grain sizes for surfaces with Rrms > 1 nm. We also observed that the differences between Au and Ag surfaces are dominated by differences in the even-numbered SAMs, but this difference vanishes with shorter molecular chain length (≤C3).


ADP-ribose contributions to genome stability and PARP enzyme trapping on sites of DNA damage; paradigm shifts for a coming-of-age modification.
ADP-ribose is a versatile modification that plays a critical role in diverse cellular processes. The addition of this modification is catalyzed by ADP-ribosyltransferases, among which notable poly(ADP-ribose) polymerase (PARP) enzymes are intimately involved in the maintenance of genome integrity. The role of ADP-ribose modifications during DNA damage repair is of significant interest for the proper development of PARP inhibitors targeted toward the treatment of diseases caused by genomic instability. More specifically, inhibitors promoting PARP persistence on DNA lesions, termed PARP "trapping," is considered a desirable characteristic. In this review, we discuss key classes of proteins involved in ADP-ribose signaling (writers, readers, and erasers) with a focus on those involved in the maintenance of genome integrity. An overview of factors that modulate PARP1 and PARP2 persistence at sites of DNA lesions is also discussed. Finally, we clarify aspects of the PARP trapping model in light of recent studies that characterize the kinetics of PARP1 and PARP2 recruitment at sites of lesions. These findings suggest that PARP trapping could be considered as the continuous recruitment of PARP molecules to sites of lesions, rather than the physical stalling of molecules. Recent studies and novel research tools have elevated the level of understanding of ADP-ribosylation, marking a coming-of-age for this interesting modification.


Load-Independent Systolic and Diastolic Right Ventricular Function in Heart Failure With Preserved Ejection Fraction as Assessed by Resting and Handgrip Exercise Pressure-Volume Loops.
Although systolic right ventricular (RV) dysfunction has been shown to be a potent predictor for adverse outcomes in patients with heart failure with preserved ejection fraction (HFpEF), RV functional abnormalities in the course of the syndrome are not well characterized. We, therefore, sought to assess load-independent and load-dependent systolic and diastolic characteristics of RV function in stable outpatients with HFpEF. We invasively obtained RV and left ventricular pressure-volume loops in 24 HFpEF patients and 9 patients without heart failure symptoms with a conductance catheter during basal conditions and handgrip exercise. Transient preload reduction was used to extrapolate the RV end-systolic elastance and diastolic stiffness constant. HFpEF patients and controls showed similar left ventricular and RV dimensions and ejection fractions with elevated left ventricular filling pressures. In HFpEF patients, invasively determined load-independent RV contractility (P=0.04) and load-independent passive RV stiffness constant β (P<0.01) were elevated. Although RV relaxation and cardiac output were similar at baseline, HFpEF patients demonstrated a blunted increase in cardiac output under exercise (P=0.01) associated with prolonged RV relaxation (P=0.01), decrease in stroke volume (P<0.01), higher RV-filling pressures (P<0.01), and a marked increase in the end-diastolic pressure-volume relationship (P<0.01). In compensated stages of the HFpEF syndrome, systolic RV function is preserved, but diastolic abnormalities with intrinsic RV stiffness and prolonged RV relaxation are already present. Impaired diastolic RV reserve contributes to a blunted increase in cardiac output during exertion. Because impairments in diastolic function seem to be a biventricular phenomenon, RV diastolic dysfunction warrants further consideration when characterizing HFpEF patients. https://www.clinicaltrials.gov. Unique identifier: NCT02459626.


Comparison between epidural and intravenous analgesia effects on disease-free survival after colorectal cancer surgery: a randomised multicentre controlled trial.
Thoracic epidural analgesia (TEA) has been suggested to improve survival after curative surgery for colorectal cancer compared with systemic opioid analgesia. The evidence, exclusively based on retrospective studies, is contradictory. In this prospective, multicentre study, patients scheduled for elective colorectal cancer surgery between June 2011 and May 2017 were randomised to TEA or patient-controlled i.v. analgesia (PCA) with morphine. The primary endpoint was disease-free survival at 5 yr after surgery. Secondary outcomes were postoperative pain, complications, length of stay (LOS) at the hospital, and first return to intended oncologic therapy (RIOT). We enrolled 221 (110 TEA and 111 PCA) patients in the study, and 180 (89 TEA and 91 PCA) were included in the primary outcome. Disease-free survival at 5 yr was 76% in the TEA group and 69% in the PCA group; unadjusted hazard ratio (HR): 1.31 (95% confidence interval [CI]: 0.74-2.32), P=0.35; adjusted HR: 1.19 (95% CI: 0.61-2.31), P=0.61. Patients in the TEA group had significantly better pain relief during the first 24 h, but not thereafter, in open and minimally invasive procedures. There were no differences in postoperative complications, LOS, or RIOT between the groups. There was no significant difference between the TEA and PCA groups in disease-free survival at 5 yr in patients undergoing surgery for colorectal cancer. Other than a reduction in postoperative pain during the first 24 h after surgery, no other differences were found between TEA compared with i.v. PCA with morphine.


What counts as evidence for working memory training? Problems with correlated gains and dichotomization.
The question of whether computerized cognitive training leads to generalized improvements of intellectual abilities has been a popular, yet contentious, topic within both the psychological and neurocognitive literatures. Evidence for the effective transfer of cognitive training to nontrained measures of cognitive abilities is mixed, with some studies showing apparent successful transfer, while others have failed to obtain this effect. At the same time, several authors have made claims about both successful and unsuccessful transfer effects on the basis of a form of responder analysis, an analysis technique that shows that those who gain the most on training show the greatest gains on transfer tasks. Through a series of Monte Carlo experiments and mathematical analyses, we demonstrate that the apparent transfer effects observed through responder analysis are illusory and are independent of the effectiveness of cognitive training. We argue that responder analysis can be used neither to support nor to refute hypotheses related to whether cognitive training is a useful intervention to obtain generalized cognitive benefits. We end by discussing several proposed alternative analysis techniques that incorporate training gain scores and argue that none of these methods are appropriate for testing hypotheses regarding the effectiveness of cognitive training.


Dosage rapide du propofol dans les matrices biologiques et les cheveux par hs-gc/ms.
This paper proposes an original method for the determination of propofol in biological specimens. For example, hair specimens are cut into small pieces and incubated overnight in Soerensen buffer at 40°C. After headspace preparation of the biological specimens spiked with tetrahydrofurane (internal standard), the analytes are transfered to the gas chromatograph and separated on a HP Wax capillary column. Detection is achieved in SIM mode (propofol : m/z 117, 163 and 178) on a mass spectrometer operating in electronic impact mode. The developped procedure is easy (full-automated), rapid (no extraction- or derivatization-step), sensible and accurate. After validation of the analytical method (linearity, extraction recovery, repetability, limit of detection), this new procedure was applied to forensic cases.


Protein kinase C promotes arachidonate mobilization through enhancement of CoA-independent transacylase activity in platelets.
A role for protein kinase C in arachidonate mobilization was demonstrated. Treatment of rat platelets with phorbol myristate acetate (PMA) or the diacylglycerol 1-oleoyl-2-acetylglycerol increased the transfer rate of arachidonate (AA) from phosphatidylcholine to phosphatidylethanolamine and stimulated AA release. The transfer dose-dependently induced by PMA was inhibited by staurosporine. Ether phospholipids were the acceptors of AA in these stimulated transfer reactions. Membrane-bound protein kinase C activity was enhanced by PMA, and this increase was inhibited by staurosporine. AA transfer between phospholipids is due to the action of polyunsaturated-fatty-acid-specific transacylases. For this purpose, transacylase activities were assayed in cell-free systems from PMA-treated platelets. We observed that the CoA-independent transacylase activity was modulated in parallel to AA transfer as a function of PMA concentration. Taken together, the data show that protein kinase C activation might promote the mobilization of AA in platelets through the enhancement of CoA-independent transacylase activity.


The Otago Exercise Program: Innovative Delivery Models to Maximize Sustained Outcomes for High Risk, Homebound Older Adults.
It is estimated one in two adults age 80 and over fall each year, resulting in substantial morbidity and mortality rates among this oldest-old population. The Otago Exercise program (OEP) is an evidence-based fall prevention program shown to reduce falls by 35% among high-risk older adults. The OEP was designed to be delivered in the home by physical therapists. This model has encountered multiple implementation challenges in the United States health-care system, which has resulted in the development and testing of innovative models to support a broader reach and dissemination of this program. The Northwest Senior and Disability Services is an Area Agency on Aging (AAA) serving a five-county region in Oregon. This AAA developed a model where a Certified Occupational Therapy Assistant (COTA) and exercise physiologist delivered the OEP with a physical therapist available to consult on all cases. Physical function assessments and self-reported perceptions about physical function were collected at baseline and 6 months. Baseline measures were collected on 239 participants enrolled in the OEP, and 62 participants at 6 months. Those who completed 6 months of the OEP demonstrated significant improvements in all physical function assessments and self-perceived functional improvements. A subset of this group that demonstrated improvements in the ability to rise from a chair also reported significantly fewer falls during the 6-month intervention. Innovative models in which the OEP exercise sessions are delivered by non-physical therapists appear to be effective in improving physical performance measures and decreasing fall risk over a 6-month period. Because these models do not require a physical therapist, they may require fewer resources to implement. These findings have implications to inform implementation and dissemination strategies to bring the OEP to scale.


Variability of Eustachian tube function in children with secretory otitis media. Evaluations at tube insertion and at follow-up.
Despite the variable clinical course of diseases related to Eustachian tube function, the variability of tubal function has been less focused than outcomes of single tests. This study aimed to compare the passive and active tubal function and its variability in children with secretory otitis media (SOM) at tube insertion and at follow-up. Thirty-eight ears in 19 children aged 4-10 years (mean 7.0 years) with long-standing SOM were examined 4-6 h after tube insertion, at 4 months and at 9 months. The pressure in the middle ear and the nasopharynx were recorded while performing (1) forced opening test, (2) equalization of +100 and -100 daPa, (3) Valsalva test, and (4) sniff test. The procedure was repeated after 30 min. Relationships were analyzed by uni- and multi-variate analysis of variance. From tube insertion to 4 months, the mean forced opening pressure increased from 282+/-128 to 355+/-153 daPa (P<0.01), and the mean closing pressure from 91+/-51 to 126+/-82 daPa (P<0.01). There was no further change at 9 months. Female gender, serous effusion (in contrast to mucoid), and more than three previous episodes of acute otitis media were related to higher opening and closing pressures. At tube insertion, 60% and 16% equalized +100 and -100 daPa, respectively, and 28% succeeded in performing Valsalva inflation. The sniff test was positive in 32%, indicating a closing failure. These rates did not change significantly over time. For individual ears, outcomes of all tests varied considerably when retested after 30 min; P(o) changed by +/-12% and P(c) by +/-26%, and 9-29% of the ears changed from a positive to negative response, or vice versa, in the equalization, Valsalva, and sniff tests. The unexpected finding of weaker closing forces at the day of tube insertion and increased tubal resistance at follow-up might be ascribed to changes in the muco-adhesive forces related to the disease and tube treatment. The pronounced intra-individual variability of test outcomes indicates that tubal function is dynamic and variable in ears prone to SOM, which emphasizes that results of single tubal function tests have very low prognostic value.


Extreme social isolation, use of community-based senior support services, and mortality among African American elderly women.
The effect of extreme social isolation and use of community-based senior services on longevity was examined in a national sample of African American elderly women (ages 55-96). Consistent with previous research on the social integration/mortality link, African American elderly women who were extremely socially isolated were hypothesized to have a higher 5-year mortality rate. It was also hypothesized that use of community senior services would be negatively associated with 5-year mortality. Results of logistic regression analysis controlling for age, education, income, and health status found that extremely socially isolated African American elderly women were three times more likely than the nonisolated women to die within the 5-year period from the initial survey. Use of community senior services did not have a relationship on mortality. Results are discussed in terms of directions for future research and intervention.


Effects of acid-etching solutions on human enamel and dentin.
Nine noncarious human molars were extracted and stored in saline solution. Three standard occlusal cavities with beveled enamel margins were prepared on each tooth and etched with the etching solutions of three dentinal adhesive systems: (1) 37% phosphoric acid solution, (2) 4.3% oxalic acid and 2.6% aluminum salts solution, and (3) 10% maleic acid solution. Scanning electron microscopic analysis revealed that all the etching solutions affected the enamel surface morphology. The solution of oxalic acid and aluminum salts removed primarily the prism core material and partially the periphery of the prisms, but did not affect the nonbeveled enamel surface. Phosphoric and maleic acids removed both prism core materials and prism periphery; these specimens also showed areas in which no prism morphology could be detected. These two acids also removed apatite crystals from the prism core of the intact enamel surface.


Assessment of neutrophil to lymphocyte ratio and mean platelet volume in pediatric familial Mediterranean fever patients.
Blood neutrophil to lymphocyte ratio (NLR) and mean platelet volume (MPV) both have been used as a simple marker of inflammation in many disorders. Here, we aimed to investigate the relationship between NLR, MPV, and familial Mediterranean fever (FMF). In this retrospective study, the files of FMF patients in pediatric rheumatology outpatient clinic were reviewed. There were 160 participants (68.4%) in the FMF patient group and 74 participants (31.6%) in the control group. Ninety of patients were in attack-free period, and 70 were in attack period. The highest values of NLR were found in the patients at attack period. Patients in attack-free period and the participants in control group had similar levels of NLR (1.71 ± 0.83 and 1.91 ± 1.86 respectively) (P = 0.457), and they had lower ratios than the patients did at attack period (4.10 ± 3.11) (P < 0.001 for both). There was no significant difference between MPV values of attack patients (8.35 ± 4.91) and attack-free patients (8.43 ± 1.15) (P = 0.074). MPV values of attack patients and attack-free patients were significantly higher than control group (7.99 ± 0.81) (P < 0.001 for both). NLR ratio may indicate FMF attack period. Since there was no significant difference between attack-free patients and control groups, NLR ratio cannot be used as a subclinical inflammation marker. However, NLR could be a useful predictor of inflammation in FMF patients. On the other hand, since our attack and attack-free patients have similar MPV values and both had greater MPV values than control group, we suggest that MPV may be used to show subclinical inflammation.


Nitrogen and phosphorus effluent loads from a paddy-field district adopting collective crop rotation.
Japanese paddy rice systems commonly adopt the rotation of vegetables, wheat and soybeans with paddy rice. Crop rotation may, however, increase the nutrient load in effluent discharged from the district because more fertilizer is applied to the rotation crops than is applied to paddy crops. We investigated a paddy-field district subject to collective crop rotation and quantified the annual nutrient load of effluent from the district in three consecutive years. The total annual exports of nitrogen and phosphorus over the investigation period ranged from 30.3 to 40.6 kg N ha(-1) and 2.62 to 3.13 kg P ha(-1). The results suggest that rotation cropping increases the effluent nutrient load because applied fertilizer is converted to nitrate, and surface runoff is increased due to the absence of shuttering boards at the field outlets.


BsmI polymorphism in the vitamin D receptor gene is associated with leg extensor muscle strength in elderly men.
Sarcopenia is defined as a reduction in skeletal muscle mass, strength, and endurance observed with advancing age. Although Vitamin D receptor (VDR) polymorphism is reported to be associated with muscle mass and strength, evidence for this is limited and conflicting. In this study, we examined the association between the polymorphisms of VDR gene BsmI, TaqI and FokI and muscular mass and strength in elderly men. This is a cross-sectional study conducted in a university hospital. One hundred and twenty men over 65 years of age participated, all participants were active men living independently in Istanbul, who were followed as outpatients in geriatric polyclinics. Most common diagnoses were hypertension, hyperlipidemia, and mild to moderate osteoarthritis. Morbid obese patients were not included in the study. Genomic DNA was extracted from peripheral blood, and VDR genotypes were determined by the polymerase chain reaction. The peak torque of the knee flexors and extensors was measured on a Cybex 350 dynamometer. Body muscle mass was calculated by using bioelectric impedance analysis. The extensor strength of the knee was higher in BB homozygotic men than in the Bb/bb group. No significant association was found with TaqI and FokI haplotypes. There was no significant association between muscle mass and strength, or between muscle mass and VDR genotype. Our data suggest that VDR gene BsmI polymorphism is associated with muscular strength in elderly men.


The effects of in utero bisphenol A exposure on ovarian follicle numbers and steroidogenesis in the F1 and F2 generations of mice.
Bisphenol A (BPA) is a commonly used plasticizer. Previous studies show that in utero exposure to BPA affects reproductive outcomes in the F1-F3 generations of mice. However, its multigenerational effects on ovarian histology and steroidogenesis over the reproductive lifespan are unknown. Thus, we tested the hypothesis that BPA has multigenerational effects on follicle numbers and steroidogenesis. Mice were exposed in utero to vehicle control or BPA (0.5, 20, and 50μg/kg/day). Ovaries were collected for histological and gene expression analyses and sera were collected for hormone assays. In utero BPA exposure decreased preantral follicle numbers, cytochrome P450 aromatase mRNA levels, and estradiol levels in the F1 generation, whereas it decreased testosterone levels and altered steroidogenic acute regulatory protein, cytochrome P450 cholesterol side-chain cleavage, 3β-hydroxysteroid dehydrogenase 1, and cytochrome P450 aromatase mRNA levels in the F2 generation. These data suggest that BPA has multigenerational effects on the ovary in mice.


Effect of fluoride application during radiotherapy on enamel demineralization.
Radiation-related caries are one the most undesired reactions manifested during or after head and neck radiotherapy. Fluoride application is an important strategy to reduce demineralization and enhance remineralizaton. To evaluate the effect of the topical application of fluoride during irradiation on dental enamel demineralization. Thirty molars were randomly divided into three groups: Non-irradiated (NI), Irradiated (I), Irradiated with fluoride (IF). Each group was subdivided according to the presence or absence of pH-cycling (n=5). In the irradiated groups, the teeth received 70 Gy. The enamel's chemical composition was measured using Fourier Transform Infrared Spectrometry (organic matrix/mineral ratio - M/M and relative carbonate content - RCC). Vickers microhardness (VHN) and elastic modulus (E) were evaluated at three depths (surface, middle and deep enamel). Scanning electron microscopy (SEM) was used to assess the enamel's morphology. The FTIR analysis (M/M and RCC) showed significant differences for irradiation, pH-cycling and the interaction between factors (p<0.001). Without pH-cycling, IF had the lowest organic matrix/mineral ratio and relative carbonate content. With pH-cycling, the organic matrix/mineral ratio increased and the relative carbonate content decreased, except for IF. VHN was influenced only by pH-cycling (p<0.001), which generated higher VHN values. ANOVA detected significant differences in E for irradiation (p<0.001), pH-cycling (p<0.001) and for the interaction between irradiation and pH-cycling (p<0.001). Increased E was found for group I without pH-cycling. With pH-cycling, groups I and IF were similar, and showed higher values than NI. The SEM images showed no morphological changes without pH-cycling. With pH-cycling, fluoride helped to maintain the outer enamel's morphology. Fluoride reduced mineral loss and maintained the outer morphology of irradiated and cycled enamel. However, it was not as effective in preserving the mechanical properties of enamel. Radiotherapy altered the enamel's elastic modulus and its chemical composition.


[Interventional therapy for liver metastases].
Interventional radiology offers not only local but also loco-regional therapeutic concepts for the treatment of liver metastases. While the local concepts are employed as image-guided, interstitial techniques, a vascular access is ideal for the loco-regional distribution of anti-tumour drugs. In the present article interstitial employed ablation methods such as radiofrequency ablation, laser-induced thermotherapy and CT-guided brachytherapy are evaluated on the basis of the available literature. The field of loco-regional vascular techniques contributes analyses of intra-arterial chemotherapy via minimally invasively implanted port systems as well as transarterial chemoembolization.


99mTc-pertechnetate uptake in parotid acinar cells by the Na+/K+/Cl- co-transport system.
99mTc-Pertechnetate (99mTcO4-) has widespread clinical use in the diagnosis and evaluation of dysfunctions in many different tissues. However, despite the broad clinical application of this radionuclide, very little is known about the mechanism by which 99mTcO4- enters a cell. We report evidence here that 99mTcO4- shares the Na+/K+/Cl- co-transport system localized to the basolateral membrane of rat parotid acinar cells. 99mTcO4- uptake by these cells was quite rapid (t1/2 approximately 30 s), was completely inhibited by the loop diuretics furosemide and bumetanide, and was markedly dependent on the presence of Na+, K+, and Cl- in the extracellular medium. Relative to uptake measured in the presence of physiological extracellular salt concentrations (Hanks' salts), 99mTcO4- uptake was inhibited 80% by sodium replacement and 50% by potassium replacement. When Cl- was replaced with the physiologically inert anion gluconate a threefold stimulation in 99mTcO4- uptake resulted. These observations provide strong evidence that 99mTcO4- can substitute for Cl- as a substrate for the Na+/K+/Cl- co-transporter and indicate that 99mTcO4- uptake by salivary glands (e.g., as seen with salivary scintiscans), and possibly by a variety of other tissues, reflects the functional activity of this co-transport mechanism.


Flipping the Dental Anatomy Classroom.
The development of cognitive knowledge, motor skills, and artistic sense in order to restore lost tooth structure is fundamental for dental professionals. The course of dental anatomy is taught in the initial years of dental school, and is a component of the basic core sciences program in the faculties of dentistry. The learning objectives of the dental anatomy course include identifying anatomical and morphological characteristics of human primary and permanent teeth; identifying and reproducing tooth surface details in order to recognize and diagnose anatomical changes; and developing student's psychomotor skills for restoring teeth with proper form and function. The majority of dental schools rely on traditional methods to teach dental anatomy, using lectures to convey the theoretical component; whereas the practical component uses two-dimensional drawing of teeth, identification of anatomical features in samples of preserved teeth, and carving of teeth. The aim of the present literature review is to summarize different educational strategies proposed or implemented to challenge the traditional approaches of teaching dental anatomy, specifically the flipped classroom educational model. The goal is to promote this approach as a promising strategy to teaching dental anatomy, in order to foster active learning, critical thinking, and engagement among dental students.


Properties of chicken lens MIP channels reconstituted into planar lipid bilayers.
Membrane fractions highly enriched in chicken lens MIP (MIP28) were found to form ion channels when incorporated into planar lipid bilayers. The channels displayed prominent unitary conductances of about 60 and 290 pS in symmetric 150 mm KCl solution and were slightly anion selective. For both depolarizing and hyperpolarizing voltages, voltage sensitivity of the MIP28-induced conductance could be fit by a Boltzmann relation, symmetric around zero mV, with V0 = 18.5 mV, n = 4.5 and gmin/gmax = 0.17. Channel properties were not appreciably altered by pH in the range of 5.8 to 7, although channel incorporation was observed to occur more frequently at lower pH values. Calcium, at millimolar concentrations, decreased the channel mean open time. Partial proteolysis of MIP28 to yield MIP21 did not appreciably affect single-channel conductance or voltage sensitivity of the reconstituted channels. MIP28 was not phosphorylated by cAMP dependent protein kinase (PKA). Although unitary conductance and selectivity of the chicken MIP channel are similar to those reported for the bovine MIP (MIP26), the voltage sensitivity of MIP28 was higher than that of the bovine homologue, and voltage sensitivity of MIP28 was not modulated by treatments previously shown to affect MIP26 voltage gating (partial proteolysis and protein phosphorylation by PKA: (Ehring et al., 1990). The existence of such strikingly different functional properties in highly homologous channel isoforms may provide a useful system for exploration of the structure-function relations of MIP channels.


The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network.
The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.