Protection of arsenic-induced hepatic disorder by arjunolic acid.
Arsenic is one of the ubiquitous environmental pollutants, which affects nearly all organ systems. The present study has been carried out to investigate the hepatoprotective role of arjunolic acid, a triterpenoid saponin, against arsenic-induced oxidative damages in murine livers. Administration of sodium arsenite at a dose of 10 mg/kg body weight for 2 days significantly reduced the activities of antioxidant enzymes, superoxide dismutase, catalase, glutathione S-transferase, glutathione reductase and glutathione peroxidase as well as depleted the level of reduced glutathione and total thiols. In addition, sodium arsenite also increased the activities of serum marker enzymes, alanine transaminase and alkaline phosphatase, enhanced DNA fragmentation, protein carbonyl content, lipid peroxidation end-products and the level of oxidized glutathione. Studies with arjunolic acid show that in vitro it possesses free radical-scavenging and in vivo antioxidant activities. Treatment with arjunolic acid at a dose of 20 mg/kg body weight for 4 days prior to arsenic administration prevents the alterations of the activities of all antioxidant indices and levels of the other parameters studied. Histological studies revealed less centrilobular necrosis in the liver treated with arjunolic acid prior to arsenic intoxication compared to the liver treated with the toxin alone. Effects of a known antioxidant, vitamin C, have been included in the study as a positive control. In conclusion, the results suggest that arjunolic acid possesses the ability to attenuate arsenic-induced oxidative stress in murine liver probably via its antioxidant activity.


Congenital hydrocephalus secondary to prenatal intracranial haemorrhage.
A high incidence of intracranial haemorrhage in utero of uncertain aetiology has been previously identified as an important cause of stillbirth in infants of immigrant Pacific Islanders in New Zealand. Congenital hydrocephalus is now described as a consequence of intracranial haemorrhage in 2 stillborn Pacific Islander infants. A large intracerebral haemorrhage, hydrocephalus and hydrops in one infant was first recognized prenatally by ultrasonography and caused intrauterine death at 26 weeks' gestation. Severe hydrocephalus in the other infant was first identified just before labour at term but the pathological findings were of old intraventricular haemorrhage with narrowing of the aqueduct of Sylvius as a reaction to the haemorrhage. Prior intracranial haemorrhage may be the cause of an increased incidence of hydrocephalus in Pacific Islander stillbirths and of some otherwise unexplained cases of congenital hydrocephalus in other races.


Feature Interaction Augmented Sparse Learning for Fast Kinect Motion Detection.
The Kinect sensing devices have been widely used in current Human-Computer Interaction entertainment. A fundamental issue involved is to detect users' motions accurately and quickly. In this paper, we tackle it by proposing a linear algorithm, which is augmented by feature interaction. The linear property guarantees its speed whereas feature interaction captures the higher order effect from the data to enhance its accuracy. The Schatten-p norm is leveraged to integrate the main linear effect and the higher order nonlinear effect by mining the correlation between them. The resulted classification model is a desirable combination of speed and accuracy. We propose a novel solution to solve our objective function. Experiments are performed on three public Kinect-based entertainment data sets related to fitness and gaming. The results show that our method has its advantage for motion detection in a real-time Kinect entertaining environment.


The Journal of Anatomy: origin and evolution.
The Journal of Anatomy was launched 150 years ago as the Journal of Anatomy and Physiology, in an age when anatomy and physiology were not regarded as separate disciplines. European science in general was advancing rapidly at the time (it was 7 years after publication of Darwin's Origin of Species), and the recent demise of the Natural History Review meant that there was no English language publication covering these subjects. The founding editors were George Murray Humphry of Cambridge and William Turner of Edinburgh, together with Alfred Newton of Cambridge and Edward Perceval Wright of Dublin (the last two served only for a year). The pivotal event leading to the Journal's foundation was the 1866 meeting of the British Association, at which Humphry delivered the 'Address in Physiology' (printed in the first issue). Turner, who was also present at the 1866 British Association meeting, remained as a member of the editorial team for 50 years and was a major contributor of Journal articles. The title was changed to Journal of Anatomy in October 1916, when it was taken under the wing, in terms of both management and ownership, by the Anatomical Society. This article reviews the early years of the Journal's publication in more detail than later years because of the historical interest of this less familiar material. The subject matter, which has remained surprisingly consistent over the years, is illustrated by examples from some notable contributions. The evolution of illustration techniques is surveyed from 1866 to the present day; the final section provides brief summaries of all of the chief editors.


Effects of subthalamic nucleus deep brain stimulation on emotional working memory capacity and mood in patients with Parkinson's disease.
In Parkinson's disease (PD), cognitive symptoms and mood changes may be even more distressing for the patient than motor symptoms. Our aim was to determine the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on working memory (WM) and mood. Sixteen patients with PD were assessed with STN-DBS switched on (DBS-ON) and with dopaminergic treatment (Med-ON) compared to switched off (DBS-OFF) and without dopaminergic treatment (Med-OFF). The primary outcome measures were a Visual Analog Mood Scale (VAMS) and an emotional 2-back WM task at 12 months after DBS in the optimal DBS-ON/Med-ON setting compared to DBS-OFF/Med-OFF. Comparison of DBS-OFF/Med-OFF to DBS-ON/Med-ON revealed a significant increase in alertness (meanoff/off =51.59±24.54; meanon/on =72.75; P=0.016) and contentedness (meanoff/off =38.73±24.41; meanon/on =79.01±17.66; P=0.001, n=16), and a trend for reduction in sedation (P=0.060), which was related to stimulation as shown in a subgroup of seven patients. The N-back task revealed a significant increase in accuracy with DBS-ON/Med-ON compared to DBS-OFF/Med-OFF (82.0% vs 76.0%, respectively) (P=0.044), regardless of stimulus valence. In line with previous studies, we found that patients rated themselves subjectively as more alert, content, and less sedated during short-term DBS-ON. Accuracy in the WM task increased with the combination of DBS and medication, possibly related to higher alertness of the patients. Our results add to the currently mixed results described for DBS on WM and suggest that there are no deleterious DBS effects on this specific cognitive domain.


Borromean sheets assembled by self-supporting argentophilic interactions.
An infinite two-dimensional Borromean coordination framework, stabilized by argentophilic interactions, was obtained by the reaction of a flexible ligand with AgBF4.


Cytomegalovirus infection in seronegative patients treated with prophylaxis: case-controlled study.
Primary cytomegalovirus (CMV) infection is common in infancy with approximately 90% to 95% of subjects developing antibodies against this virus. CMV seronegative renal allograft recipients generally receive this infection with a graft or with blood transfusions, showing a high morbidity and mortality. Prophylaxis in these patients has shown good results; however, the published studies have included a small number of patients. Our case-controlled study evaluated 163 kidney transplant recipients: 76 seronegatives for CMV and 87 seropositive for CMV as controls. The evaluated parameters were: CMV infection, CMV disease, renal function, and survival of the patient and graft. We studied our experience among CMV seronegative patients treated with various prophylaxis guidelines. Our conclusions were that CMV prophylaxis in seronegative patients was effective because it showed a risk of infection that was equal (or even less) than that in seropositive patients and revealed a delay in the onset of the disease. CMV seronegativity may be a positive prognostic factor for graft survival.


Allergic rhinitis: Disease characteristics and coping measures in Saudi Arabia.
Despite allergic rhinitis (AR) being a highly prevalent disease, according to literature, it is often underdiagnosed or undertreated. This study explored the disease characteristics of AR in the Saudi community and the non-conventional coping measures used to alleviate symptoms. The study was a nationwide cross-sectional study, using a self-report electronic survey distributed via social media networks in 2018. The survey included an explanatory letter and consent. The sample size comprised 3,458 participants and 2,849 adults had at least one of the four signs of AR, i.e. watery-nose, sneezing, nasal obstruction, itchy nose, watery eyes, in the past year, not related to cold/flu. The outcomes of the study were the triggers, pattern, severity and the classification of AR (2016 ARIA guidelines) and coping measures. Descriptive statistics, univariate analytic statistics and binary logistic regression analyses were conducted. The P-value was considered statistically significant at <0.05. The leading reported trigger of AR was dust (74%, n = 2118), followed by pollen (17%, n = 477), mold (5%, n = 140) and fur (4%, n = 114). The prevalence of intermittent AR was (54%, n = 1,635), while that of persistent AR was (46%, n = 1,314). Almost one-third (34%, n = 959) complained of mild forms of AR, while others complained of moderate to severe forms (66%, n = 1890). The coping measures were mainly shower/humidification 368(12.9%) and herbal hot drinks 266(9.3%). Older participants (adj.OR = 1.3[1.1-1.5]) and overweight participants, (adj.OR = 1.2[1.1-1.4]) reported more persistent forms of rhinitis compared to their counter groups, (adj.P<0.001 and adj.P = 0.032) respectively. Female participants (adj.OR = 0.8[0.7-0.9]) had significantly milder forms of AR, in comparison to males, adj.P = 0.006. This study presented the disease characteristics of self-reported AR and its associated factors in Saudi Arabia. Special attention should be paid to older age groups and overweight patients who reported persistent forms of AR. Males reported more severe and persistent forms of AR.


'It is a difficult topic' - a qualitative study of midwives´ experiences with routine antenatal enquiry for intimate partner violence.
Intimate partner violence (IPV) during pregnancy may jeopardize maternal and fetal health (IJFWM 49:159-164, 2004; IJGO 133:269-276, 2016). In recognition of the significant public health impact of IPV, the Norwegian Directorate of Health issued new guidelines in 2014, which recommend that health professionals routinely ask all women in antenatal care about their exposure to violence. The objective of this study was to gain an in-depth understanding of midwives' experiences with routine enquiry for intimate partner violence during the antenatal period. The study had a qualitative design. Individual semi-structured interviews with eight midwives providing antenatal care at eight Mother and Child Health Centres (MCHC) in Norway were conducted. Graneheim and Lundmans method of content analysis inspired the analysis. Three main themes emerged: Midwives do ask about violence; It can be a challenge; and Factors that make it easier to ask. All midwives enquired, but not on a regular basis, about violence. The midwives' personal interest in the topic was an important factor that made it easier for them to ask about violence. Lack of time, fear of not knowing how to deal with a positive answer and lack of organizational support were barriers to asking pregnant women about their experiences of violence. Midwives were aware of the guidelines and made some efforts to implement them. However, further education and organisational support is needed to enable midwives to routinely ask all pregnant women about IVP.


Associations of biochemical changes and maternal traits with mutation 1843 (C>T) in the RYR1 gene as a common cause for porcine stress syndrome.
Stress syndrome is usually caused by a mutation in the ryanodine receptor gene (ryr1) and it is widely studied in humans and swine populations. The protein product of this gene plays a crucial role in the regulation of calcium transport in muscle cells. A G>T mutation in the human ryr1 gene, which results in the replacement of a conserved arginine at position 614 where a leucine occurs at the same position as the previously identified Arg→Cys mutation reported in all cases of porcine stress syndrome (PSS). Porcine stress syndrome affects biochemical pathways in stress-susceptible individuals during a stress episode and some biochemical parameters that were used as markers for diagnostic purposes. Also, PSS has remarkable influence on the maternal characteristics of sows. This study dealt with different genotypes for PSS and its association with possible biochemical changes and maternal traits of sows. Seventy-three reproductive sows genotyped for PSS by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were included in this survey. Sixty of them were stress-free (NN), 11 were heterozygous carriers (Nn) and two animals were homozygous (nn) for the 1843 (C>T) mutation. Significant differences in non stress induced animals with different PSS genotypes were found in the values of creatine phoshokinase (CPK), lactate dehydrogenase (LDH), alkaline phosphatase (AP) and aspartate aminotransferase (AST). Regarding the maternal traits, our study showed that stress susceptible animals (nn) have an increased number of stillborn piglets and a reduced number of newborn piglets compared with heterozygous and normal animals.


Activation of the renin-angiotensin system in high fructose-induced metabolic syndrome.
High fructose intake induces hyperglycemia and hypertension. However, the mechanism by which fructose induces metabolic syndrome is largely unknown. We hypothesized that high fructose intake induces activation of the renin-angiotensin system (RAS), resulting in hypertension and metabolic syndrome. We provided 11-week-old Sprague-Dawley rats with drinking water, with or without 20% fructose, for two weeks. We measured serum renin, angiotensin II (Ang II), and aldosterone (Aldo) using ELISA kits. The expression of RAS genes was determined by quantitative reverse transcription polymerase chain reaction. High fructose intake increased body weight and water retention, regardless of food intake or urine volume. After two weeks, fructose intake induced glucose intolerance and hypertension. High fructose intake increased serum renin, Ang II, triglyceride, and cholesterol levels, but not Aldo levels. High fructose intake increased the expression of angiotensinogen in the liver; angiotensin-converting enzyme in the lungs; and renin, angiotensin II type 1a receptor (AT1aR), and angiotensin II type 1b receptor (AT1bR) in the kidneys. However, expression of AT1aR and AT1bR in the adrenal glands did not increase in rats given fructose. Taken together, these results indicate that high fructose intake induces activation of RAS, resulting in hypertension and metabolic syndrome.


The effect of the cell death suppressor vMIA on the production of a recombinant protein in the adenovirus-293 expression system.
Apoptosis is a major problem in animal cell cultures during production of biopharmaceuticals, such as recombinant proteins or viral vectors. A 293 cell line constitutively expressing vMIA (viral mitochondria-localized inhibitor of apoptosis) was constructed and examined on production of a model recombinant protein, green fluorescent protein (GFP) in the adenovirus-293 expression system, and on production of a model infectious adenoviral vector. vMIA-293 cells were more resistant than the parental 293 cells to apoptosis induced by either oxidative stress, or by adenovirus infection. The yield of GFP produced in vMIA-293 cell cultures was consistently higher (approximately 140%) compared to that in the parental cells. vMIA reduced production of adenovirus infectious particles, which was not due to a decline of adenovirus replication, since adenoviral DNA replication rate in vMIA-293 cells was higher than that in the parental cells. In conclusion, introduction of the vMIA gene into the 293 cell line is a promising strategy to improve recombinant protein production in the adenovirus-293 expression system.


Gender differences in a sample of vocational rehabilitation clients with TBI.
Because traumatic brain injury affects between 1.5 and 2 million individuals per year and results in long term vocational and financial difficulties, there is growing interest in determining those factors that predict successful outcomes for specific groups of individuals with TBI. An NIH consensus panel on TBI has suggested that women are one group that needs more attention, particularly given the studies indicating that men and women experience different cognitive [14], emotional [19], and vocational outcomes following TBI [5]. The current study evaluated differences in injury severity, demographics, neuropsychological abilities, and vocational and financial outcomes for 78 persons with TBI (55 male, 23 female) who received services from a state Vocational Rehabilitation Division (DVR). Despite similar injury severity, neuropsychological and demographic characteristics, more men (43.6%) received Maintenance services from MO-DVR than women (21.7%). Of note, only 4.4% of the women were successfully employed through DVR, compared to 23.6% of the men. In addition, 73.9% of the women had services terminated after being accepted by DVR but before services were initiated, compared to 56.4% of the men. The significance of these results is discussed, as are the limitations of the current project.


Neither heavy nor light load resistance exercise acutely exacerbates lymphedema in breast cancer survivor.
Resistance exercise has great potential to aid in the management of breast cancer-related lymphedema (BCRL), but little is known regarding the acute response of performing resistance exercises with the affected limb. To examine the acute impact of upper body resistance exercise on the amount of swelling and severity of symptoms in women with BCRL and to compare these effects between resistance exercise involving high and low loads (heavier vs lighter weights). Seventeen women aged 61 ± 9 years with mild to severe BCRL participated in this study. Participants completed a high load (6-8 repetition maximum) and low load (15-20 repetition maximum) exercise session consisting of 2 sets of 5 upper body resistance exercises in a randomized order separated by a 10- to 12-day wash-out period. The extent of swelling was assessed using bioimpedance spectroscopy, dual-energy x-ray absorptiometry, and arm circumference measurements. The severity symptoms were assessed using the visual analogue scale (pain, heaviness, and tightness) and a modified Brief Pain Inventory. Measurements were taken pre-exercise, immediately post-exercise, 24 hours post-exercise, and 72 hours post-exercise. No changes in the extent of swelling or the severity of symptoms were observed between pre-exercise and immediately post-exercise, 24 hours post-exercise, or 72 hours post-exercise. No differences in the response to the high or low load exercise were observed. Upper body resistance exercise does not acutely increase swelling or feelings of discomfort/pain, heaviness tightness in the affected limb of BCRL patients when performed at either high or low loads.


Long non‑coding RNAs and microRNAs as regulators of stress in cancer (Review).
Resistance to stress is a feature of cancer cells. Cellular stress includes oxidative, metabolic and genotoxic stress conditions, which under normal conditions lead to cell death. However, in contrast to normal cells, cancer cells overcome the checkpoints that normally restrict growth, and are able to resist cellular stress and subsequent cell death through a variety of mechanisms, which include several non‑coding RNAs (ncRNAs). Within this context, long ncRNAs (lncRNAs) and microRNAs (miRNAs/miRs) are the main categories of ncRNAs that have been shown in the literature to function as regulators of stress resistance pathways in cancer. miRNAs play a key role in the majority of biological pathways, as they regulate the expression of hundreds of target genes, including genes involved in stress response and cell death, oncogenes, or tumor suppressor genes, by inhibiting protein translation or promoting the degradation of mRNAs. Respectively, lncRNAs are epigenetic regulators, which are also involved in cancer progression, stress response and metabolic pathways by promoting or inhibiting the transcription, splicing, translation and modulation of protein function. Thus, the present review summarizes recent knowledge related to the role of these molecules in the cancer response to stress, highlighting the ability of these non‑coding molecules to be effective drug targets and biomarkers in cancer treatment.


Dermatomyositis and polymyositis in childhood.
From January 1, 1981 to December 31, 1992, we experienced nine patients with childhood onset of dermatomyositis and polymyositis. The mean age of disease onset was 12 years (range 7 to 16 years). Seven of them fulfilled the criteria of dermatomyositis, the remaining two were polymyositis. Girls were more predominant than boys in 6:3 ratio. The clinical features included extremities muscle weakness, skin rash, periorbital swelling and dysphagia. Increased muscle enzymes including creatine phosphokinase (CPK) or lactic dehydrogenase (LDH) were all positive in nine patients. All of our nine patients were treated with prednisolone after the diagnosis was established. The duration of treatment ranged from 3 to 65 months (mean: 25.3 months). Two of the nine patients also received immunosuppressive agents, hydroxychloroquine and azathioprine respectively. At present six patients survive without treatment. Two patients continue with corticosteroid and immunosuppressive therapy. One patient died from primary peritonitis, six months after being diagnosed with JDMS. In conclusion our study shows there is a female dominance; monocyclic clinical course is more common; and the prognosis is good in general, in the cases of juvenile dermatomyositis and polymyositis.


Sutures and iris wound-healing in the baboon.
This paper reports an experimental study of iris wound-healing and the response of iris tissue in baboons to different suture materials following a planned surgical incision. The wound was sutured with 8-0 virgin silk, 22 mum Ethilon or 7-0 chromacised catgut, or left unsutured. The iris produces a minimal inflammatory response to aseptic trauma characterised by round cell infiltration, clump cell proliferation, pigment cell proliferation from the posterior epithelial surface and proliferation of non-pigmented ciliary epithelium (knots). This response is associated with microscopic hemorrhages in the iris. There does not appear to be any fibrous union of wound edges, instead the wound surfaces become lined with a layer of pigmented cells, probably from the posterior epithelium. Sutures play the dual role of accurately apposing the wound edges and, because there is no fibrous union of iris tissue, of keeping them in apposition. Therefore, they must remain in situ permanently. Catgut is poorly tolerated by the iris and is eventually absorbed. For these two reasons it is unsuitable. Ethilon is the least reactive and virgin silk only slightly more reactive. Both of these are suitable for iris suture. The suture material at present available is not entirely satisfactory. Finer suture material is required to reduce even more the iris response to sutures. Needles, even those supplied with Ethilon or virgin silk, are too large and clumsy. The answer to this problem probably lies in strengthening and sharpening the suture material ends so that they can act as needles.


[Evaluation of peritoneal lavage smears and gastric wall brushing smears in gastric cancer surgery].
We investigated the utility of intraoperative peritoneal lavage smears and gastric wall brushing smears for diagnosis of peritoneal dissemination and serosal involvement during gastric cancer surgery. One hundred fifty-three patients with gastric cancer were examined; 138 who underwent gastric resection and 15 who did not. The incidence of cancer cell positivity determined by these methods was 8.0% in resected cases, and 80.0% in unresected cases. According to macroscopic serosal invasion, the incidence of positive cytology was 0% for S0, 15.4% for S1, 13.0% for S2, and 38.7% for S3. According to microscopic wall invasion, the incidence of positivity was 0% for m and sm, 6.3% for mp, 0% for ss, and 22.2% for se and si. In terms of macroscopic peritoneal dissemination, the incidence of positivity was 2.6% for P0, 28.6% for P1, 42.9% for P2, and 90.0% for P3. These results suggest that peritoneal lavage smears and gastric wall brushing smears are useful for predicting the spread of peritoneal dissemination. Thus, further study of intraoperative fast-smear cytology seems warranted.


The Need for Action: Addressing Inhalant Abuse and Whitener Addiction Among Adolescents.
Inhalant abuse and whitener addiction are serious problems among adolescents that have significant consequences for physical and mental health, as well as for families, communities, and society as a whole. This review article discusses the causes and health consequences of inhalant abuse and whitener addiction among adolescents, as well as the challenges in addressing the problem. The paper also outlines strategies for addressing inhalant abuse and whitener addiction, including education and awareness campaigns; early intervention and treatment; collaboration between schools, healthcare providers, and community organizations; and support for families affected by inhalant abuse and addiction. The paper concludes with a call to action for policymakers, healthcare providers, and community members to prioritize and address inhalant abuse and whitener addiction among adolescents. By working together, we can help to prevent substance abuse and promote the health and well-being of our youth.


Temporal response of positive and negative regulators in response to acute and chronic exercise training in mice.
Angiogenesis is controlled by a balance between positive and negative angiogenic factors, but temporal protein expression of many key angiogenic regulators in response to exercise are still poorly defined. In C57BL/6 mice, we evaluated the temporal protein expression of several pro-angiogenic and anti-angiogenic factors in response to (1) a single acute bout of exercise and (2) chronic exercise training resulting from 3, 5, 7, 14 and 28 days of voluntary wheel running. Following acute exercise, protein levels of vascular endothelial growth factor-A (VEGF), endostatin and nucleolin were increased at 2-4 h (P < 0.05), whereas matrix metalloproteinase (MMP)-2 was elevated within a 12-24 h window (P < 0.05). Training increased muscle capillarity 11%, 15% and 22% starting with 7, 14 and 28 days of training, respectively (P < 0.01). Basal VEGF and MMP-2 were increased by 31% and 22%, respectively, compared to controls (P < 0.05) after 7 days (7d) training, but decreased to back to baseline after 14d training. After 28d training VEGF fell 49% below baseline control (P < 0.01). Basal muscle expression of thrombospondin 1 (TSP-1) was ∼900% greater in 14d- and 28d-trained mice compared to either 5d- and 7d-trained mice (P < 0.05), and tended to increase by ∼180-258% compared to basal control levels (P < 0.10). The acute responsiveness of VEGF to exercise in untrained mice (i.e. 161% increase, P < 0.001) was lost with capillary adaptation occurring after 7, 14 and 28d training. Taken together, these data support the notion that skeletal muscle angiogenesis is controlled by a balance between positive and negative mitogens, and reveals a complex, highly-coordinated, temporal scheme whereby these factors can differentially influence capillary growth in response to acute versus chronic exercise.


Yiqi Huoxue Recipe Regulates Autophagy through Degradation of Advanced Glycation End Products via mTOR/S6K1/LC3 Pathway in Diabetic Nephropathy.
Yiqi Huoxue recipe can delay the progression of diabetic nephropathy, but its treatment mechanism is still unclear. We aimed to explore the effects of Yiqi Huoxue recipe on autophagy in diabetic nephropathy and its underlying mechanism. All rats were randomly divided into seven groups. The body weight, kidney weight, blood glucose, glycated hemoglobin, urine protein, urine microprotein, creatinine, urea nitrogen, triglyceride, and lipoprotein were analyzed. HE, Masson, and periodic acid-Schiff staining were used to detect the severity of pathological changes in kidneys. The level of advanced glycation end products was assessed by the ELISA. Immunofluorescence staining was performed to check the expressions of podocin and nephrin. The expression levels of mTOR/S6K1/LC3 pathway-related proteins and mRNA were detected by qRT-PCR and western blotting. Yiqi Huoxue recipe significantly elevated body weight and significantly decreased kidney weight and kidney index. Yiqi Huoxue recipe significantly affected the levels of biochemical indicators in diabetic nephropathy and showed a regulatory effect on kidney damage and lipid metabolism disorders. ELISA showed that Yiqi Huoxue recipe significantly reduced the level of advanced glycation end products. The expressions of nephrin and podocin increased significantly, depending on the dosage of Yiqi Huoxue recipe. Additionally, Yiqi Huoxue recipe regulated the expression levels of p-AKT, mTOR, S6K1, and LC3. Yiqi Huoxue recipe regulates podocyte autophagy to promote the degradation of advanced glycation end products through mTOR/S6K1/LC3 pathway. It has a certain guiding significance for the diagnosis and treatment of diabetic nephropathy.


Effects of Regulated Deficit Irrigation on Amino Acid Profiles and Their Derived Volatile Compounds in Cabernet Sauvignon (Vitis vinifera L.) Grapes and Wines.
Amino acid contents and their derived volatile compositions in Cabernet Sauvignon grapes and wines after regulated deficit irrigation (RDI) were investigated during the 2015 and 2016 growing seasons in Yinchuan (NingXia, China). High-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) were used for amino acid and volatile compound analyses. Three RDI strategies were tested: 60% (RDI-1), 70% (RDI-2), and 80% (RDI-3) of grapevine estimated evapotranspiration (ETc), and 100% ETc was used as the control group (CK). RDI-treated vines had lower yields and berry weights with higher total soluble solids than the control treatment. RDI-1 increased proline levels in berries and wines. RDI-2 enhanced tyrosine and asparagine levels in wines. RDI-3 enhanced arginine, alanine, valine, leucine, and isoleucine levels in berries and wines. RDI-2 and RDI-3 increased the concentrations of 2-methyl-1-butyl acetate, benzaldehyde, 3-methyl-1-pentanol, and 3-methyl-1-butanol in wines. The accumulation of volatile compounds was closely related to the amino acid concentrations-especially isoleucine, valine, and leucine-in grapes. Our results showed that RDI treatments altered amino acid concentrations and their derived volatile compositions in wines.


What is a geriatrician?
A geriatrician is something more than a physician who simply cares for old people. The geriatrician should, above all, be well grounded in internal medicine, have a genuine fondness for the elderly and their problems, and be experienced in neurology, psychiatry and rehabilitation medicine. A possible additional role is that of organizer and coordinator of health services for old people.


Update on pruritic mechanisms of hypertrophic scars in postburn patients: the potential role of opioids and their receptors.
Although itching (or pruritus) in a scar is a very common and distressing symptom and is increasingly being recognized as a significant obstacle in burn rehabilitation, the exact mechanisms underlying this symptom have not been elucidated; hence, a reliable therapy has not been established. Recent findings have suggested that itching caused by inflammatory dermatosis can be reduced by antihistamines, but histamine antagonists cannot block all types of pruritus (eg, neuropathic itch). This indicates the presence of a histamine-independent pathway for itch. Itch or pruritus may also be evoked by direct activation of opioid receptors, which have recently been identified in the skin. This article aims to assess the current state of knowledge regarding the role of opioids in the generation of itch in hypertrophic scars in postburn patients. To this end, the authors have reviewed the relevant literature and present some clinical data. The authors hope that this review will form the basis for future research to elucidate the mechanism and treatment of itch.


In vitro fermentation characteristics, in vivo ileal and total tract nutrient digestibilities, and fecal microbiota responses of dogs to α-cyclodextrin.
The objectives were to examine in vitro fermentation characteristics, in vivo nutrient digestibility, fecal microbiota, and serum lipid profiles as affected by α-cyclodextrin (ACD) supplementation. Short-chain fatty acid (SCFA) production was measured after in vitro fermentation for 3, 6, 9, and 12 h of ACD, β-cyclodextrin, and γ-cyclodextrin. Five mixed-breed hounds were used in a Latin square design. Each experimental period comprised 14 d, including 10 d for diet adaptation and 4 d for fecal collection. Dogs were fed, twice a day, an extruded diet made with poultry byproduct meal and brewer's rice as the main ingredients. Dogs were supplemented with 0, 1, 2, 3, or 4 g of ACD diluted in 15 mL of water twice daily for a total of 0, 2, 4, 6, and 8 g ACD/d. Maximal in vitro production of total SCFA was lowest for ACD. However, the greatest maximal production of propionate was noted for ACD treatment. Total tract nutrient digestibility and fecal DM concentration linearly decreased ( < 0.05) for treatment groups receiving ACD; no changes were observed for ileal digestibility. Serum cholesterol and triglyceride concentrations were within normal ranges for dogs and were not different among treatments. Similarly, no changes in fecal microbiota were observed. Overall, ACD supplementation appears to have no effect on nutrient absorption in the small intestine but may alter fermentation in the large bowel, which could lead to a higher proportion of propionate production as observed in the in vitro experiment.


Anarchy Is a Molecular Signature of Worker Sterility in the Honey Bee.
Worker sterility is a defining characteristic of eusociality. The existence of the sterile worker caste remains a fundamental question for evolutionary biology as it requires the existence of genes that reduce personal reproduction. Currently, little is known about the proximate mechanisms underpinning worker sterility. Studies into a mutant "anarchistic" strain (in which workers can activate their ovaries) of honey bee, Apis mellifera, identified a list of candidate genes that regulate ovary activation. We quantified the expression of the four most promising candidate genes (Anarchy, Pdk1, S6k, and Ulk3) in nonactivated and activated ovaries of wild-type workers. Ovarian expression of Anarchy, a peroxisomal membrane protein, predicts the ovary state of workers with 88.2% accuracy. Increased expression of Anarchy in the ovary is strongly associated with suppression of oogenesis and its expression is sensitive to the presence of the queen. Therefore, Anarchy satisfies key criteria for a "gene underlying altruism". When we knocked down expression of Anarchy in the ovary using RNA interference (RNAi) we altered the expression of Buffy, a gene that regulates programmed cell death. Whole-mount multiplex fluorescent in situ hybridization (mFISH) shows Anarchy transcripts localize to degenerating oocytes within the ovary. Our results suggest that Anarchy is involved in the regulation of oogenesis through programmed cell death. The evolution of facultative worker sterility most likely occurred when the conserved mechanism of programmed cell death was co-opted to regulate ovary activation. Anarchy may therefore be the first example of a gene that has evolved through kin selection to regulate worker sterility.


Parents' and healthcare professionals' experiences of care after stillbirth in low- and middle-income countries: a systematic review and meta-summary.
Stillbirth has a profound impact on women, families, and healthcare workers. The burden is highest in low- and middle-income countries (LMICs). There is need for respectful and supportive care for women, partners, and families after bereavement. To perform a qualitative meta-summary of parents' and healthcare professionals' experiences of care after stillbirth in LMICs. Search terms were formulated by identifying all synonyms, thesaurus terms, and variations for stillbirth. Databases searched were AMED, EMBASE, MEDLINE, PsychINFO, BNI, CINAHL. Qualitative, quantitative, and mixed method studies that addressed parents' or healthcare professionals' experience of care after stillbirth in LMICs. Studies were screened, and data extracted in duplicate. Data were analysed using the Sandelowski meta-summary technique that calculates frequency and intensity effect sizes (FES/IES). In all, 118 full texts were screened, and 34 studies from 17 countries were included. FES range was 15-68%. Most studies had IES 1.5-4.5. Women experience a broad range of manifestations of grief following stillbirth, which may not be recognised by healthcare workers or in their communities. Lack of recognition exacerbates negative experiences of stigmatisation, blame, devaluation, and loss of social status. Adequately developed health systems, with trained and supported staff, are best equipped to provide the support and information that women want after stillbirth. Basic interventions could have an immediate impact on the experiences of women and their families after stillbirth. Examples include public education to reduce stigma, promoting the respectful maternity care agenda, and investigating stillbirth appropriately. Reducing stigma, promoting respectful care and investigating stillbirth have a positive impact after stillbirth for women and families in LMICs.


Early stages of formation of branched host-guest supramolecular polymers.
A structural characterization of host-guest supramolecular copolymers, formed by an adamantane dimer and two beta-cyclodextrin trimers in aqueous solution, has been carried out by combining small angle X-ray scattering and light scattering experiments. A shape-reconstruction method was applied to the SAXS data to obtain relatively high-resolution conformation information, and a correlation with the experimental dynamic light scattering results was performed, by estimating the hydrodynamic radii of the reconstructed shape through a shell model method. When applied on the solutions of the trimers, the analysis provides a globular reconstructed shape with a hydrodynamic radius in agreement with the experimental one. For the polymers, elongated structures were inferred which grow both in length and in cross section by increasing the concentration. Depending on the beta-cyclodextrin trimer employed in the polymer preparation, polymerization degrees ranging between roughly 7 and 14 or 9 and 22 were obtained in the concentration range 4.00-10.0 or 3.10-6.60 mM of the trimer (6.00-15.0 or 4.65-9.90 mM of the dimer). Aggregation schemes were proposed accounting for the formation of hyperbranched, linear, and network like polymers. The experimental results are not far from those expected on the basis of the aggregation in hyperbranched structure, for which the growth of elongated aggregates can be predicted in the early stages of the polymerization. However, the coexistence of the other structures, in particular of the linear one, cannot be ruled out.


Chronic Undiagnosed Brucellosis Presenting as Sciatica.
Brucellosis is a common zoonotic disease in southern Europe. Although having the potential to harm several anatomic regions and systems, musculoskeletal manifestations are rare, usually involving the spine and the sacroiliac joints. In the literature, the reports of hip manifestations are sporadic. We present a case report of chronic, undiagnosed brucellosis indirectly affecting the hip joint. A 51-years-old male patient was admitted to our department with acute onset sciatica. His medical history was remarkable for incomplete cauda equina syndrome of unknown etiology and concomitant dura mater disruption, creating local sinuses resulting at the right buttock. On radiological evaluation, we demonstrated multiple abscesses of the lower lumbar spine and the ipsilateral sacroiliac joint, along with sinuses communicating with the right hip joint capsule. Soft and osseous tissue cultures obtained from the area of the lesion were negative for common bacteria. Considering the patient's history, chronicity of the disease, and the lesional pattern, we suspected brucellosis as a possible etiological factor. Laboratory evaluation with the serum agglutination test confirmed the diagnosis. The patient denied the surgical treatment, so we proceeded with chronic suppression antibiotics schemes. On 12-month follow-up, the patient has no clinical signs of infection relapse; he has reasonable pain control and a normal gait. Indirect hip infection due to chronic brucellosis is rare, and physicians should be very suspicious of the disease's characteristic radiological manifestations to reach a correct diagnosis.


Glenoid Bone Loss in Posterior Shoulder Instability: Prevalence and Outcomes in Arthroscopic Treatment.
Glenoid bone loss is a well-accepted risk factor for failure after arthroscopic stabilization of anterior glenohumeral instability. Glenoid bone loss in posterior instability has been noted relative to its existence in posterior instability surgery. Its effect on outcomes after arthroscopic stabilization has not been specifically evaluated and reported. The purpose was to evaluate the presence of posterior glenoid bone loss in a series of patients who had undergone arthroscopic isolated stabilization of the posterior labrum. Bone loss was then correlated to return-to-duty rates, complications, and validated patient-reported outcomes. Case-control study; Level of evidence, 3. A retrospective review was conducted at a single military treatment facility over a 4-year period (2010-2013). Patients with primary posterior instability who underwent arthroscopic isolated posterior labral repair were included. Preoperative magnetic resonance imaging was used to calculate posterior glenoid bone loss using a standardized "perfect circle" technique. Demographics, return to duty, complications, and reoperations, as well as outcomes scores including the Single Assessment Numeric Evaluation and the Western Ontario Shoulder Instability Index (WOSI) scores, were obtained. Outcomes were analyzed across all patients based on percentage of posterior glenoid bone loss. Bone loss was then categorized as below or above the subcritical threshold of 13.5% to determine if bone loss effected outcomes similar to what has been shown in anterior instability. There were 43 consecutive patients with primary, isolated posterior instability, and 32 (74.4%) completed WOSI scoring. Mean follow-up was 53.7 months (range, 25-82 months) The mean posterior glenoid bone loss was 7.3% (0%-21.5%). Ten of 32 patients (31%) had no appreciable bone loss. Bone loss exceeded 13.5% in 7 of 32 patients (22%), and 2 patients (6%) exceeded 20% bone loss. Return to full duty or activity was nearly 90% overall. However, those with >13.5%, subcritical glenoid bone loss, were statistically less likely to return to full duty (relative risk = 1.8), but outcomes scores, complications, and revision rates were otherwise not different in those with no or minimal bone loss versus those with more significant amounts. Posterior glenoid bone loss has not previously been evaluated independently relative to patients with shoulder instability repairs. Sixty-nine percent of our patients had measurable bone loss, and 22% had greater than 13.5%, or above subcritical bone loss. While these patients were statistically less likely to return to full duty, the reoperation rate, complications, and patient-reported outcomes between groups were not different.


Immune mechanisms in murine gammaherpesvirus-68 infection.
The murine gamma-herpesvirus-68 (MHV-68) is a relative of the Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) that infects mice. All these gamma-herpesviruses are subject to immune control, but limit the impact of this control through immune evasion. Molecular evasion mechanisms have been described in abundance. However, we can only speculate what EBV and KSHV immune evasion contributes to the viral lifecycle. With MHV-68, we can analyze in vivo the contribution of immunological and virological gene expression to pathogenesis. While the physiology of infection seems quite well conserved between these viruses, the pathologies associated with immune suppression are obviously very different. MHV-68 is therefore more suited to uncovering the basic biology of gamma-herpesvirus infection than to testing disease interventions. Nevertheless, it may make some useful predictions about effective strategies of vaccination and infection control. This review aims to outline our current state of knowledge and to highlight some limitations of the MHV-68 model as it stands, in the hope of stimulating constructive progress.


Inhibition and axial deviation of limb regeneration in the newt by means of a digit implanted into the amputated limb.
This research was designed to follow up the observation of Thornton and Kraemer ('51) that regressed, denervated limbs of Ambystoma larvae will not regenerate upon reinnervation if all digits on the limbs were not completely resorbed. The object of this experiment was to determine whether the presence of an apical structure, protruding past the amputation surface, would affect the regenerative process. Both forearms of adult newts were amputated midway between the elbow and the wrist. One limb served as a normal regeneration control, and in the other limb the third digit from the removed hand was implanted in place of the removed radius, so that the three distal phalangeal segments protruded past the plane of amputation. Blastema formation in the experimental limbs was delayed by several weeks as compared with control limbs. Approximately one third of the experimental limbs did not regenerate. The regenerates that did form were strongly deviated (45-90 degrees) radially from the longitudinal axis of the limb. Experimental analysis showed that the delay in regeneration is due largely to the projecting part of the digit. The radial deviation of the regenerates is not due to the digital implant, but rather to the removal of the radius. Trauma alone does not account for this phenomenon.


High-resolution melting analysis of the common c.1905+1G>A mutation causing dihydropyrimidine dehydrogenase deficiency and lethal 5-fluorouracil toxicity.
Dihydropyrimidine dehydrogenase (DPD) deficiency is a pharmacogenetic syndrome associated with life-threatening toxicity following exposure to the fluoropyrimidine drugs 5-fluorouracil (5-FU) and capecitabine (CAP), widely used for the treatment of colorectal cancer and other solid tumors. The most prominent loss-of-function allele of the DPYD gene is the splice-site mutation c.1905+1G>A. In this study we report the case of a 73-year old woman with metastatic colorectal cancer who died from drug-induced toxicity after the first cycle of 5-FU-containing chemotherapy. Her symptoms included severe neutropenia, thrombocytopenia, mucositis and diarrhea; she died 16 days later despite intensive care measures. Post-mortem genetic analysis revealed that the patient was homozygous for the c.1905+1G>A deleterious allele and several family members consented to being screened for this mutation. This is the first report in Spain of a case of 5-FU-induced lethal toxicity associated with a genetic defect that results in the complete loss of the DPD enzyme. Although the frequency of c.1905+1G>A carriers in the white population ranges between 1 and 2%, the few data available for the Spanish population and the severity of this case prompted us to design a genotyping procedure to prevent future toxic effects of 5-FU/CAP. Since our group had previously developed a high-resolution melting (HRM) assay for the simultaneous detection of KRAS, BRAF, and/or EGFR somatic mutations in colorectal and lung cancer patients considered for EGFR-targeted therapies, we included the DPYD c.1905+1G>A mutation in the screening test that we describe herein. HRM provides a rapid, sensitive, and inexpensive method that can be easily implemented in diagnostic settings for the routine pre-therapeutic testing of a gene mutation panel with implications in the pharmacologic treatment.


Characterization of Salmonella Typhimurium isolates associated with septicemia in swine.
Salmonella Typhimurium is frequently isolated from pigs and may also cause enteric disease in humans. In this study, 33 isolates of S. Typhimurium associated with septicemia in swine (CS) were compared to 33 isolates recovered from healthy animals at slaughter (WCS). The isolates were characterized using phenotyping and genotyping methods. For each isolate, the phage type, antimicrobial resistance, and pulsed-field gel electrophoresis (PFGE) DNA profiles were determined. In addition, the protein profiles of each isolate grown in different conditions were studied by Coomassie Blue-stained sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot. Various phage types were identified. The phage type PT 104 represented 36.4% of all isolates from septicemic pigs. Resistance to as many as 12 antimicrobial agents, including some natural resistances, was found in isolates from CS and WCS. Many genetic profiles were identified among the PT 104 phage types. Although it was not possible to associate one particular protein with septicemic isolates, several highly immunogenic proteins, present in all virulent isolates and in most isolates from clinically healthy animals, were identified. These results indicated that strains associated with septicemia belong to various genetic lineages that can also be recovered from asymptomatic animals at the time of slaughter.


A heterologous prime-boost Ebola virus vaccine regimen induces durable neutralizing antibody response and prevents Ebola virus-like particle entry in mice.
Ebola virus (EBOV) is one of the most virulent pathogens known to humans. Neutralizing antibodies play a major role in the protection against EBOV infections. Thus, an EBOV vaccine capable of inducing a long-lasting neutralizing antibody response is highly desirable. We report here that a heterologous prime-boost vaccine regimen can elicit durable EBOV-neutralizing antibody response in mice. A chimpanzee serotype 7 adenovirus expressing EBOV GP (denoted AdC7-GP) was generated and used for priming. A truncated version of EBOV GP1 protein (denoted GP1t) was produced at high levels in Drosophila S2 cells and used for boosting. Mouse immunization studies showed that the AdC7-GP prime/GP1t boost vaccine regimen was more potent in eliciting neutralizing antibodies than either the AdC7-GP or GP1t alone. Neutralizing antibodies induced by the heterologous prime-boost regimen sustained at high titers for at least 18 weeks after immunization. Significantly, in vivo challenge studies revealed that the entry of reporter EBOV-like particles was efficiently blocked in mice receiving the heterologous prime-boost regimen even at 18 weeks after the final dose of immunization. These results suggest that this novel AdC7-GP prime/GP1t boost regimen represents an EBOV vaccine approach capable of establishing long-term protection, and therefore warrants further development.


Increased expression of ferritin, an iron-storage protein, in specific regions of the parahippocampal cortex of epileptic rats.
Iron accumulation in the brain has been associated with neurodegenerative disorders, including epilepsy. In our previous SAGE study, we showed that ferritin, an iron-storage protein, was one of the genes (Ferritin-H) that showed overexpression before the chronic epileptic phase. In this study we used ferritin as indicator for disturbed iron homeostasis to acquire insight into whether this could play a role in the pathogenesis of temporal lobe epilepsy. With immunocytochemistry, we studied the regional and cellular distribution of ferritin protein in an animal model for temporal lobe epilepsy in which spontaneous seizures develop a few weeks after electrically induced status epilepticus (SE). Increased ferritin expression was observed in regions known to be vulnerable to cell death, mainly in reactive microglial cells of epileptic rats. Ferritin expression after SE was initially high, especially throughout the hippocampus, but decreased over time. In the chronic epileptic phase, it was still upregulated in regions where extensive cell loss occurs during the early acute and latent period. Within the parahippocampal region, the most persistent ferritin overexpression was present in microglial cells in layer III of the medial entorhinal area. The upregulation was most extensive in rats that had developed a progressive form of epilepsy with frequent seizures (approximately five to 10 seizures per day). The fact that ferritin upregulation is still present in specific limbic regions in chronic epileptic rats, when neuronal loss is absent or minimal, suggests a role of iron in the pathogenesis and progression of epilepsy.


Gene replacement strategies for lung cancer.
Considerable evidence has accumulated that cancer has a genetic origin based on the development of somatic mutations in families of genes responsible for critical functions of cellular DNA repair, growth control, and division. Restoration of the function of a single pivotal gene product appears sufficient to mediate antitumor effects that are potentially clinically significant. For example, restoration of wild-type p53 function in the cancer cell by gene transfer is sufficient to cause either cell-cycle arrest or apoptosis. This effect is not restricted to p53 but has been observed for oncogenes and other tumor suppressor genes as well. Genes can be delivered with sufficient efficiency by direct intratumoral injection to mediate tumor regression as shown in preclinical studies and phase I clinical trials in non-small cell lung cancer. Although clinical trials of gene replacement are in the earliest stages, this treatment offers a unique mechanism of action with a potentially high therapeutic index.


Apnea-hypopnea threshold for CO2 in patients with congestive heart failure.
To understand the pathogenesis of central sleep apnea (CSA) in patients with congestive heart failure (CHF), we measured the end-tidal carbon dioxide pressure (PET(CO2)) during spontaneous breathing, the apnea-hypopnea threshold for CO2, and then calculated the difference between these two measurements in 19 stable patients with CHF with (12 patients) or without (7 patients) CSA during non-rapid eye movement sleep. Pressure support ventilation was used to reduce the PET(CO2) and thereby determine the thresholds. In patients with CSA, 1.5-3% CO2 was supplied temporarily to stabilize breathing before determining the thresholds. Unlike patients without CSA whose eupneic PET(CO2) increased during sleep (37.7 +/- 1.4 mm Hg versus 40.2 +/- 1.5 mm Hg, p < 0.01), patients with CSA showed no rise in PET(CO2) from wakefulness to sleep (37.5 +/- 0.9 mm Hg versus 38.2 +/- 1.0 mm Hg, p = 0.2). Patients with CHF and CSA had their eupneic PET(CO2) closer to the threshold PET(CO2) than patients without CSA (DeltaPET(CO2) [eupneic PET(CO2) - threshold PET(CO2)] was 2.8 +/- 0.3 mm Hg versus 5.1 +/- 0.7 mm Hg for apnea, p < 0.01; 1.7 +/- 0.7 versus 4.1 +/- 0.5 mm Hg for hypopnea, p < 0.05). In summary, patients with CHF and CSA neither increase their eupneic PET(CO2) during sleep nor proportionally decrease their apnea-hypopnea threshold. The resultant narrowed DeltaPET(CO2) predisposes the patient to the development of apnea and subsequent breathing instability.


Erythropoietin attenuates motor neuron programmed cell death in a burn animal model.
Burn-induced neuromuscular dysfunction may contribute to long-term morbidity; therefore, it is imperative to develop novel treatments. The present study investigated whether erythropoietin (EPO) administration attenuates burn-induced motor neuron apoptosis and neuroinflammatory response. To validate our hypothesis, a third-degree hind paw burn rat model was developed by bringing the paw into contact with a metal surface at 75°C for 10 s. A total of 24 male Sprague-Dawley rats were randomly assigned to four groups: Group A, sham-control; Group B, burn-induced; Group C, burn + single EPO dose (5000 IU/kg i.p. at D0); and Group D, burn + daily EPO dosage (3000 IU/kg/day i.p. at D0-D6). Two treatment regimens were used to evaluate single versus multiple doses treatment effects. Before sacrifice, blood samples were collected for hematological parameter examination. The histological analyses of microglia activation, iNOS, and COX-2 in the spinal cord ventral horn were performed at week 1 post-burn. In addition, we examined autophagy changes by biomarkers of LC3B and ATG5. The expression of BCL-2, BAX, cleaved caspase-3, phospho-AKT, and mTOR was assessed simultaneously through Western blotting. EPO administration after burn injury attenuated neuroinflammation through various mechanisms, including the reduction of microglia activity as well as iNOS and COX-2 expression in the spinal cord ventral horn. In addition, the expression of phospho-AKT, mTOR and apoptotic indicators, such as BAX, BCL-2, and cleaved caspase-3, was modulated. Furthermore, the activity of burn-induced autophagy in the spinal cord ventral horn characterized by the expression of autophagic biomarkers, LC3B and ATG5, was reduced after EPO administration. The present results indicate that EPO inhibits the AKT-mTOR pathway to attenuate burn-induced motor neuron programmed cell death and microglia activation. EPO can modulate neuroinflammation and programmed cell death and may be a therapeutic candidate for neuroprotection.


Evidence based analysis of Cisplatin for treating patients with cutaneous squamous cell carcinoma.
This analysis was conducted to evaluate the efficacy and safety of cisplatin based chemotherapy for treating patients with cutaneous squamous cell carcinoma. Clinical studies evaluating the efficacy and safety of cisplatin based regimens on response and safety for patients with cutaneous squamous cell carcinoma were identified using a predefined search strategy. Pooled response rates (RR) of treatment were calculated. In cisplatin based regimens, 4 clinical studies which including 50 patients with advanced cutaneous squamous cell carcinoma were considered eligible for inclusion. Regimens included cisplatin, doxorubicin, or vindesine. Pooled analysis suggested that, in all patients, the pooled RR was 60% (30/50) in cisplatin based regimens. Nausea and vomiting were the main side effects. No grade III or IV renal or liver toxicity were observed. No treatment related death occurred with the cisplatin based treatments. Evidence based analysis suggests that cisplatin based regimens are associated with a good response rate and acceptable toxicity for treating patients with cutaneous squamous cell carcinoma.


[Post-traumatic stress disorder and substance use disorder: epidemiology, nature and neurobiology].
Post-traumatic stress disorder (PTSD) is frequently associated with other psychiatric diagnoses, being substance use disorder (SUD) one of the most prevailing. Comorbid disorders in general and SUD in particular frequently complicate the course and outcome of PTSD, and vice versa. As with other dual disorders, comorbidity of PTSD and SUD is complex, having been proposed different theoretical models to explain it that will be discussed in the present paper, the first of a series of two. In addition, the present paper reviews data from epidemiological studies, as well as the clinical characteristics, the relevance of stressful life events as a vulnerability factor to PTSD as well as to SUD and the neurobiological basis of the association of both disorders with the aim of gaining a better understanding of this comorbidity, so that the treatment of this dual disorder will be discussed in the second part.


Oxysterols from human bile induce apoptosis of canine gallbladder epithelial cells in monolayer culture.
Oxysterols have been detected in various mammalian organs and blood. Biliary epithelium is exposed to high concentrations of cholesterol, and we have identified three keto-oxysterols (cholest-4-en-3-one, cholesta-4,6-dien-3-one, cholesta-3,5-dien-7-one) in human bile and gallstones. Because the effects of oxysterols on biliary physiology are not well defined, we investigated their biological effects on dog gallbladder epithelial cells. Enriched medium (culture medium containing taurocholate and lecithin and cholesterol +/- various oxysterols) was applied to confluent monolayers of dog gallbladder epithelial cells in culture. Cytotoxicity and apoptosis were studied by morphological analysis and flow cytometry. Oxysterols in the mitochondrial fraction were identified by gas chromatography/mass spectrometry, whereas release of cytochrome c from mitochondria was assayed by spectrophotometry and Western blot analysis. Compared with cells treated with culture medium or with enriched medium containing cholesterol, oxysterol-treated cells showed significantly increased apoptosis (P < 0.05). Exogenously applied oxysterols were recovered from the mitochondrial fraction. Cytochrome c release from mitochondria was increased significantly by cholest-4-en-3-one, cholesta-4,6-dien-3-one, and 5beta-cholestan-3-one (all P < 0.05). Thus oxysterols recovered from human bile and gallstones induce apoptosis of biliary epithelium via a mitochondrial-dependent pathway and may play a role in the pathogenesis of chronic inflammation and carcinogenesis in the gallbladder.


Corneal stromal stem cells reduce corneal scarring by mediating neutrophil infiltration after wounding.
Corneal scarring limits vision for millions of individuals worldwide. Corneal transplantation (keratoplasty) is the standard of care for corneal opacity; however, it bears the risk of graft rejection and infection and is not universally available. Stem cell therapy holds promise as an alternative to keratoplasty. Stem cells from human corneal stroma (CSSC) induce regeneration of transparent corneal tissue in a mouse wound-healing model. In this study we investigated the mechanism by which CSSC prevent deposition of fibrotic tissue. Infiltration by CD11b+/Ly6G+ neutrophils and myeloperoxidase expression were increased in corneas 24 hr after corneal wounding but were reduced in CSSC-treated wounds. Secretion of TSG-6, a protein known to regulate neutrophil migration, was up-regulated in CSSC in response to TNFα and as CSSC differentiate to keratocytes. In vivo, wounded mouse corneas treated with CSSC contained human TSG-6. Inhibition of neutrophil infiltration into cornea by CSSC was reversed when TSG-6 expression was knocked down using siRNA. Silencing of TSG-6 expression in CSSC reduced their ability to block scarring and the expression of mRNA for fibrosis-associated proteins collagen III, tenascin C, and smooth muscle actin in wounded corneas. Neutropenic mice exhibited a significant reduction in corneal scarring and fibrotic mRNA expression 2 weeks after wounding. These results support the conclusion that neutrophil infiltration is an essential event in the fibrotic response to corneal damage and that prevention of scarring by CSSC is mediated by secretion of TSG-6 by these cells.


Differential orexin/hypocretin expression in addiction-prone and -resistant rats selectively bred for high (HiS) and low (LoS) saccharin intake.
Rats that have been selectively bred for high (HiS) saccharin intake demonstrate elevated drug-seeking behavior in several phases of addiction compared to those bred for low (LoS) saccharin intake. HiS rats also consume greater amounts of highly palatable substances compared to LoS rats; however, little is known about the neurobiological substrates moderating the divergent behaviors found between the HiS and LoS lines. Orexins are neuropeptides that have been implicated in the conditioned cue aspects of drug abuse and overconsumption of palatable substances, and differential orexin activity in the HiS and LoS phenotypes may enhance our understanding of the close relationship between food and drug reward, and ultimately food and drug addiction. The lateral hypothalamus (LH) and perifornical area (PFA) are brain regions that have been implicated in regulating feeding behavior and addiction processes, and they contain orexinergic neurons that project broadly throughout the brain. Thus, we investigated orexin and c-Fos expression in the LH and PFA using immunohistochemistry in HiS and LoS rats following either control or cocaine (15 mg/kg) injections. Results indicated that HiS rats have higher orexin-positive cell counts compared to LoS rats in both the LH and PFA, regardless of cocaine (vs. saline) treatment. In contrast, neuronal activity indicated by c-Fos expression did not differ in either of these brain areas in HiS vs. LoS rats. These results suggest that the orexin system may be involved in aspects of genetically-mediated differences in vulnerability to compulsive, reward-driven behaviors.


Sexual victimization and family violence among urban African American adolescent women: do violence cluster profiles predict partner violence victimization and sex trade exposure?
Guided by an intersectional feminist perspective, we examined sexual victimization, witnessing intimate partner violence (IPV) in the family, and familial physical abuse among a sample of 180 urban African American adolescent women. We used cluster analysis to better understand the profiles of cumulative victimization, and the relationships between profiles and IPV victimization and personal exposure to the sex trade. Just under one third of the sample reported sexual victimization, with cooccurrence with both forms of family violence common. The cluster profile with high levels of severe family violence was associated with the highest rate of IPV victimization and sex trade exposure.


Using Human Genetics to Understand Mechanisms in Ischemic Stroke Outcome: From Early Brain Injury to Long-Term Recovery.
There is a critical need to elucidate molecular mechanisms underlying brain injury, repair, and recovery following ischemic stroke-a global health problem with major social and economic impact. Despite 5 decades of intensive research, there are no widely accepted neuroprotective drugs that mitigate ischemic brain injury, or neuroreparative drugs, or personalized approaches that guide therapies to enhance recovery. We here explore novel reverse translational approaches that will complement traditional forward translational methods in identifying mechanisms relevant to human stroke outcome. Although genome-wide association studies have yielded over 30 genetic loci that influence ischemic stroke risk, only a few genome-wide association studies have been performed for stroke outcome. We discuss important considerations for genetic studies of ischemic stroke outcome-including carefully designed phenotypes that capture injury/recovery mechanisms, anchored in time to stroke onset. We also address recent genome-wide association studies that provide insight into mechanisms underlying brain injury and repair. There are several ongoing initiatives exploring genomic associations with novel phenotypes related to stroke outcome. To improve the understanding of the genetic architecture of ischemic stroke outcome, larger studies using standardized phenotypes, preferably embedded in standard-of-care measures, are needed. Novel techniques beyond genome-wide association studies-including exploiting informatics, multi-omics, and novel analytics-promise to uncover genetic and molecular pathways from which drug targets and other new interventions may be identified.


Glial kon/NG2 gene network for central nervous system repair.
The glial regenerative response to central nervous system (CNS) injury, although limited, can be harnessed to promote regeneration and repair. Injury provokes the proliferation of ensheathing glial cells, which can differentiate to remyelinate axons, and partially restore function. This response is evolutionarily conserved, strongly implying an underlying genetic mechanism. In mammals, it is elicited by NG2 glia, but most often newly generated cells fail to differentiate. Thus an important goal had been to find out how to promote glial differentiation following the proliferative response. A gene network involving Notch and prospero (pros) controls the balance between glial proliferation and differentiation in flies and mice, and promotes CNS repair at least in fruit-flies. A key missing link had been how to relate the function of NG2 to this gene network. Recent findings by Losada-Perez et al., published in JCB, demonstrated that the Drosophila NG2 homologue kon-tiki (kon) is functionally linked to Notch and pros in glia. By engaging in two feedback loops with Notch and Pros, in response to injury, Kon can regulate both glial cell number and glial shape homeostasis, essential for repair. Drosophila offers powerful genetics to unravel the control of stem and progenitor cells for regeneration and repair.


Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia.
Prepulse inhibition (PPI) of the startle reflex is modulated by a complex neural network. Prepulse inhibition impairments are found at all stages of schizophrenia. Previous magnetic resonance imaging (MRI) studies suggest that brain correlates of PPI differ between patients with schizophrenia and healthy controls; however, these studies included only patients with chronic illness and medicated patients. Our aim was to examine the structural brain correlates of PPI in antipsychotic-naive patients with first-episode schizophrenia. We performed acoustic PPI assessment and structural MRI (1.5 and 3 T) in men with first-episode schizophrenia and age-matched controls. Voxel-based morphometry was used to investigate the association between PPI and grey matter volumes. We included 27 patients and 38 controls in the study. Patients had lower PPI than controls. The brain areas in which PPI and grey matter volume correlated did not differ between the groups. Independent of group, PPI was significantly and positively associated with regional grey matter volume in the right superior parietal cortex. Prepulse inhibition and grey matter volume associations were also observed in the left rostral dorsal premotor cortex, the right presupplementary motor area and the anterior medial superior frontal gyrus bilaterally. Follow-up analyses suggested that the rostral dorsal premotor cortex and presupplementary motor area correlations were driven predominantly by the controls. We used 2 different MRI scanners, which might have limited our ability to find subcortical associations since interscanner consistency is low for subcortical regions. The superior parietal cortex seems to be involved in the regulation of PPI in controls and antipsychotic-naive men with first-episode schizophrenia. Our observation that PPI deficits in schizophrenia may be related to the rostral dorsal premotor cortex and presupplementary motor area, brain areas involved in maintaining relevant sensory information and voluntary inhibition, warrants further study.


Plasminogen-activator of the arterial wall in occluded arteries.
The plasminogen activator in 117 specimen of 20 coronary and 29 pulmonary arteries occluded completely by thrombi or emboli within the adventitia and intima was studied using TODD's histochemical method. 39 cadavers were used, 1--18 hours post mortem from subjects aged from 45 to 88 years. In occluded arteries both coronary and pulmonary the plasminogen activator activity was decreased in comparison with normal and atherosclerotic patients. In coronary and pulmonary arterial thrombi a low grade focal activity of plasminogen activator was detected. It is assumed that the decrease of plasminogen activator in the occluded human arterial wall is due to the impaired oxygen supply of the vessel wall and to the consumption of the plasminogen activator for thrombus lysis. These mechanisms are likely to influence the plasminogen activator for a certain and prolonged time, since there were no changes of fibrinolysis within the vessel wall of arteria carotis in rats where an acute thrombosis was elicited by means of an electric current.


Perturbative solution for terahertz two-wire metallic waveguides with different radii.
We introduce the technique of perturbation of boundary condition to the problem of terahertz two-wire metallic waveguides with different radii. Based on the quasi-TEM analytical mode fields derived by use of Möbius transformation, a concise expression for the complex effective index is obtained analytically. The expression is in good agreement with the simulation result. Further, the dispersion and attenuation are obtained from the expression. In addition, we find a zero value point of the group velocity dispersion around 1.268 THz. The results show that the technique of perturbation of boundary condition is helpful in the analysis and design of terahertz metal waveguide.


Renal vein extension during living-donor kidney transplantation in the era of hand-assisted laparoscopic living-donor nephrectomy.
To evaluate retrospectively the clinical outcomes of living-donor kidney transplantations (LDKTs) using renal vein extension (RVE) for donor kidneys with short renal veins. Between January 2007 and December 2010, a total of 576 LDKTs were performed with grafts generated by hand-assisted laparoscopic living-donor nephrectomy: 31 (5.4%) transplants with RVE and 545 (94.6%) without an additional vascular procedure for renal vein lengthening. Outcomes were compared in patients who did and did not undergo the RVE procedure during transplantation. The 31 transplantation patients that underwent RVE involved procured kidneys with short renal veins: 29 were right-sided kidneys (93.5%) and 2 were left-sided kidneys (6.5%) (P=0.00). The RVE grafts were obtained from allogenic gonadal veins from female donors (n=16, 51.6%) and iliac veins from deceased donors (n=15, 48.4%). There were no postoperative complications related to the RVE procedure. During a follow-up period of 45.6±15.9 months, there were one (3.2%) graft failure among the 31 patients with RVE and four (0.7%) among the 545 patients without RVE. Delayed graft function was noted in one (3.2%) of the RVE patients and 22 (4.0%) of the patients without RVE. There was no statistically significant difference in graft failure (P=0.24) or delayed graft function (P=1.00) between the two groups. During LDKT, donor kidneys with exceptionally short renal veins, which may result in unavoidable tension during renal vein anastomosis, may be modified by RVE, thus facilitating a secure anastomosis and reducing postoperative complications.


Requalification of a Brazilian Trichoderma Collection and Screening of Its Capability to Decolourise Real Textile Effluent.
Water contamination with large amounts of industrial textile coloured effluents is an environmental concern. For the treatment of textile effluents, white-rot fungi have received extensive attention due to their powerful capability to produce oxidative (e.g., ligninolytic) enzymes. In addition, other groups of fungi, such as species of Aspergillus and Trichoderma, have also been used for textile effluents treatment. The main aim of the present study was to requalify a Brazilian Trichoderma culture collection of 51 Trichoderma strains, isolated from different sources in Brazil and preserved in the oldest Latin-American Fungal Service Culture Collection, The Micoteca URM WDCM 804 (Recife, Brazil). Fungal isolates were re-identified through a polyphasic approach including macro- and micro-morphology and molecular biology, and screened for their capability to decolourise real effluents collected directly from storage tanks of a textile manufacture. Trichoderma atroviride URM 4950 presented the best performance on the dye decolourisation in real textile effluent and can be considered in a scale-up process at industrial level. Overall, the potential of Trichoderma strains in decolourising real textile dye present in textile effluent and the production of the oxidative enzymes Lac, LiP and MnP was demonstrated. Fungal strains are available in the collection e-catalogue to be further explored from the biotechnological point of view.


Influence of polarization setting on gold nanorod signal at nonplasmonic wavelengths under differential interference contrast microscopy.
Researchers rely on a variety of microscopic techniques for observing and tracking anisotropic nanoparticles in real time experiments. This technical note focuses on the optical behavior exhibited by gold nanorods at nonplasmonic wavelengths under differential interference contrast microscopy (DIC). Intense diffraction patterns appear at nonplasmonic wavelengths, and the behavior of these patterns can be altered by adjusting the surrounding medium or the polarizer setting. Such patterns are absent when linear and crossed polarizations are utilized. Making polarization adjustments is important in DIC microscopy, because it affects bias retardation and image contrast. The nonplasmonic diffraction bands that were observed could potentially be exploited for rotational tracking, but more importantly, researchers should exhibit care in selecting a nanorod sample and the polarization setting when working with DIC microscopy.


Effects of methanol extract of Uncariae Ramulus et Uncus on ibotenic acid-induced amnesia in the rat.
In the present study, we investigated the effects of Uncariae Ramulus et Uncus (UR) on learning and memory in the Morris water maze task and the central cholinergic system of rats with excitotoxic medial septum (MS) lesion. In the water maze test, the animals were trained to find a platform in a fixed position during 6 days and then received a 60-s probe trial in which the platform was removed from the pool on the 7th day. Ibotenic lesion of the MS showed impaired performance of the maze test and severe cell losses in the septohippocampal cholinergic system (SHC), as indicated by decreased choline acetyltransferase-immunoreactivity and acetylcholinesterase-reactivity in the hippocampus. Daily administrations of UR (100 mg/kg, i.p.) for 21 consecutive days produced significant reversals of ibotenic acid-induced deficit in learning and memory. These treatments also reduced the loss of cholinergic immunoreactivity in the hippocampus induced by ibotenic acid. These results demonstrated that impairments of spatial learning and memory may be attributable to degeneration of SHC neurons and that UR ameliorated learning and memory deficits partly through neuroprotective effects on the central acetylcholine system. Our studies suggest that UR may be useful in the treatment of Alzheimer's disease.


Transforming Growth Factor-β-Neutralizing Antibodies Improve Alveolarization in the Oxygen-Exposed Newborn Mouse Lung.
Abnormal alveolar formation and excessive disordered elastin accumulation are key pathological features in bronchopulmonary dysplasia. Transforming growth factor (TGF)-β is an important regulator of the extracellular matrix in the developing lung. To determine if increased TGF-β would injure alveolar development by activating TGF-β signaling and by influencing the expression of elastogenesis-related protein, we performed intraperitoneal injection of newborn mice with the TGF-β-neutralizing antibody 1D11 and observed whether 1D11 had a protective role in the oxygen (O2)-exposed newborn mouse lung. The newborn mice were exposed to 85% O2 for 14 and 21 days. 1D11 was administered by intraperitoneal injection every day from postnatal days 3 to 20. Alveolar morphology was assessed by hematoxylin and eosin staining. The expression and distribution of elastin were evaluated by immunohistochemistry. The level of TGF-β signaling-related proteins were measured by immunohistochemistry, enzyme-linked immunosorbent assay, and Western blot. The expression levels of elastogenesis-related proteins, including tropoelastin, fibulin-5, and neutrophil elastase (NE), which participate in the synthesis, assembly, and degradation of elastin, were detected by real-time PCR and Western blot. In this research, impaired alveolar development and elastin deposition as well as the excessive activation of TGF-β signaling were observed in the newborn mouse lung exposed to hyperoxia. 1D11 improved alveolarization as well as the distribution of elastin in the newborn lung with hyperoxia exposure. The expression levels of tropoelastin, fibulin-5, and NE, which are important components of elastogenesis, were decreased by treatment with 1D11 in the injured newborn lung. These data demonstrate that 1D11 improved alveolarization by blocking the TGF-β signaling pathway and by reducing the abnormal expression of elastogenesis-related proteins in the O2-exposed newborn mouse lung. 1D11 may become a new therapeutic method to prevent the development of bronchopulmonary dysplasia.


Ascending thoracic aneurysms are associated with decreased systemic atherosclerosis.
We noted clinically that patients with aortic root aneurysms and dissections seemed to have little systemic atherosclerosis. It is our objective to determine whether there is a negative association between ascending thoracic aneurysms and systemic atherosclerosis. Atherosclerosis was quantified by evaluating non-contrast CT images of the chest and scoring the degree of calcifications as a marker for atherosclerosis in the coronary arteries and aorta. The degree of calcification was compared in 64 patients with aortic root aneurysm (annuloaortic ectasia, 31 patients; type A dissection, 33 patients) vs 86 control subjects. Multivariable analysis was applied to test for an association between aortic root aneurysms and systemic calcification independent of risk factors for atherosclerosis. Multivariable analysis revealed that patients with ascending aortic aneurysms of the annuloaortic ectasia type and patients with type A dissections had significantly lower overall calcification scores in their arterial vessels compared to patients in the control group (p = 0.03 and p < 0.0001, respectively). These results were independent of all other risk factors for atherosclerosis. Smoking, dyslipidemia, diabetes, and age were all found to increase the degree of atherosclerosis (p < 0.01 to 0.05). Aortic root pathology (annuloaortic ectasia or type A dissection) is associated with decreased systemic atherosclerosis. It is possible that a mechanism exists whereby the same genetic mutations predisposing patients to ascending aortic aneurysms also exert a protective effect against systemic atherosclerosis.


Complications of Neurosurgery.
This article provides an overview of the major neurologic complications of common neurosurgical and endovascular procedures. Brain edema, seizures, postoperative hemorrhage, and cerebral ischemia can complicate neurosurgical procedures and produce neurologic decline. The high variability of reporting, types of operations, patient characteristics, and acuity of cases make estimating the incidence and severity of complications difficult. Overall, the complication rate of neurosurgical procedures is approximately 14%, but these are commonly systemic complications (eg, bleeding requiring transfusion, need for mechanical ventilation). In addition to intracranial hemorrhage, ischemia, and seizures after craniotomies, additional characteristic complications include hyperperfusion syndrome and cranial nerve palsies after carotid endarterectomy, cerebrospinal fluid leaks and aseptic meningitis after posterior fossa surgery, and arterial dissections or groin hematomas after endovascular procedures. Neurologic decline can be caused by a variety of causes in the postoperative period. The indication for surgery, type of surgery, and time of decline is helpful in narrowing the differential diagnosis. Brain edema, elevated intracranial pressure (ICP), seizures, intracranial hemorrhage, ischemic infarction, and cranial nerve palsies are some of the more common complications in patients that neurologists may be asked to evaluate or comanage in the postoperative setting.


Oxygen sensing and signal transduction in hypoxic pulmonary vasoconstriction.
Hypoxic pulmonary vasoconstriction (HPV), also known as the von Euler-Liljestrand mechanism, is an essential response of the pulmonary vasculature to acute and sustained alveolar hypoxia. During local alveolar hypoxia, HPV matches perfusion to ventilation to maintain optimal arterial oxygenation. In contrast, during global alveolar hypoxia, HPV leads to pulmonary hypertension. The oxygen sensing and signal transduction machinery is located in the pulmonary arterial smooth muscle cells (PASMCs) of the pre-capillary vessels, albeit the physiological response may be modulated in vivo by the endothelium. While factors such as nitric oxide modulate HPV, reactive oxygen species (ROS) have been suggested to act as essential mediators in HPV. ROS may originate from mitochondria and/or NADPH oxidases but the exact oxygen sensing mechanisms, as well as the question of whether increased or decreased ROS cause HPV, are under debate. ROS may induce intracellular calcium increase and subsequent contraction of PASMCs via direct or indirect interactions with protein kinases, phospholipases, sarcoplasmic calcium channels, transient receptor potential channels, voltage-dependent potassium channels and L-type calcium channels, whose relevance may vary under different experimental conditions. Successful identification of factors regulating HPV may allow development of novel therapeutic approaches for conditions of disturbed HPV.


Mast cell concentration and skin wound contraction in rats treated with Ximenia americana L.
To evaluate wound contraction and the concentration of mast cells in skin wounds treated with wild plum (Ximenia americana) essential oil-based ointment in rats. Sixty rats were submitted to two cutaneous wounds in the thoracic region, on the right and left antimeres. Thereon, they were divided into three groups: GX (wounds treated once a day with hydro alcoholic branch extract of Ximenia americana), GP (wounds that received vehicle), and GC (wounds without product application). Wounds were measured immediately after the injury as well as 4, 7, 14 and 21 days post-topical application of the extract. At these days, five rats from each group were euthanatized. Thereafter, samples were fixed in 10% formaldehyde and processed for paraffin embedding. Sections were stained with H.E, Masson's Trichrome and toluidine blue for morphological, morphometrical and histopathological analysis, under light microscopy. The degree of epithelial contraction was measured and mast cell concentrations were also evaluated with an image analyzer (Image Pro-plus®software) . The extract treated group showed lower mast cell concentrations in the 4th day of lesion, as compared to GP (GX<GP=GC, p=0.029), as well as with increased contraction at 7th and 14th days, respectively (7th and 14th days, GX > GP = GC; p<0.05) . Ointment containing 10% X. americana induces a decrease in mast cell concentration, at the beginning of the healing process, and promotes early skin wound contraction in rats.


Diagnostic decision-making in anatomic pathology.
In diagnostic pathology, decision-making skills are used to match the facts of a particular case to a diagnostic category. Ideally the diagnosis is established with "beyond a reasonable doubt" certainty, but substantial uncertainty orfrank diagnostic error can afflict the diagnostic process for a variety of reasons. Many of these diagnostic problems are explained by failures of decision-making. Unfortunately, it appears that substantial components of decision-making are too poorly understood to study or improve. For example, "instant pattern recognition," use of implicit knowledge, and use of creativity represent areas where discussion may not be helpful. In contrast, rule-based problem-solving is sufficiently well understood that the members of an almost purely cognitive specialty might be prompted to ask, what do we know about what we do when we problem-solve? This article reviews some of the more intriguing aspects of decision-making in the hope of stimulating interest in the topic among pathologists.


Drug pricing and reimbursement decision making systems in Mongolia.
It is essential to allocate available resources equitably in order to ensure accessibility and affordability of essential medicines, especially in less fortunate nations with limited health funding. Currently, transparent and evidence based research is required to evaluate decision making regarding drug registration, drug pricing and reimbursement processes in Mongolia. To assess the drug reimbursement system and discuss challenges faced by policy-makers and stakeholders. The study has examined Mongolian administrative documents and directives for stakeholders and analysed published statistics. Experts and decision-makers were interviewed about the drug pricing and reimbursement processes in Mongolia. Decisions regarding Mongolian drug registration were based on commonly used criteria of quality, safety, efficacy plus some economic considerations. A total of 11.32 billion Mongolian National Tugrugs (MNT) [5.6 million United States Dollars (USD)] or 12.1% of total health expenditure was spent on patient reimbursement of essential drugs. The highest reimbursed drugs with respect to cost in 2014 were the cardiovascular drug group. Health insurance is compulsory for all citizens; in addition all insured patients have access to reimbursed drugs. However, the decision making process, in particular the level of reimbursement was limited by various barriers, including lack of evidence based data regarding efficacy and comparative cost-effectiveness analysis of drugs and decisions regarding reimbursement. Drug registration, pricing and reimbursement process in Mongolia show an increasing trend of drug registration and reimbursement rates, along with lack of transparency. Limited available data indicate that more evidence-based research studies are required in Mongolia to evaluate and improve the effectiveness of drug pricing and reimbursement policies.


[Questionnaire of perceived quality (QQP): a study on the differences of gender].
In the present paper we analyze the psychometric properties of an Italian questionnaire measuring the perceived quality of health services (Questionnaire of Perceived Quality; Coluccia, Ferretti, Lorini, Calamai, 2002). Subjects answered 14 questions subdivided into four factors (i.e. Satisfaction regarding Medical Doctors, Nurses, Auxiliary Staff, and Hospital Structure). We administered the questionnaire to 1,600 patients in the "Le Scotte" Hospital of Siena. According to structural equation modeling, we studied the dimensionality of the questionnaire using confirmatory factor analysis and, successively, we studied differences in gender using Multi-sample analysis. Results show significant gender differences for two dimensions (i.e. Satisfaction regarding Nurses and Satisfaction regarding Hospital Structures). Females, compared to males, express more negative evaluations in these two factors.


A randomized controlled trial comparing internet and video to facilitate patient education for men considering the prostate specific antigen test.
Little is known about the relative advantages of video versus internet-based decision aids to facilitate shared medical decision making. This study compared internet and video patient education modalities for men considering the prostate specific antigen (PSA) test. Two hundred and twenty-six men, aged 50 years or older, and scheduled to complete a physical examination at an HMO Health Appraisal Clinic were randomly assigned to access a website (N = 114) or view a 23-minute videotape in the clinic (N = 112) prior to deciding whether they wanted to be screened for prostate cancer. There were no between-groups differences in participants' ratings of convenience, effort, or satisfaction following exposure to the decision aid. Participants assigned to the video group were more likely to review the materials than individuals assigned to the internet group (98.2% vs 53.5%). Participants in the video group showed significantly greater increases in PSA knowledge and were more likely to decline the PSA test than individuals assigned to the internet group. However, participants in the internet group who reviewed the entire online presentation showed similar increases in PSA knowledge as video participants. Only 5% of all participants visited other websites to inform themselves about the PSA test. Overall, the video was significantly more effective than the Internet in educating participants about benefits and risks of PSA screening.


Endoscopic pancreatic duct stents reduce the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients.
Pancreatitis is the most common and potentially serious complication of post-endoscopic retrograde cholangiopancreatography (ERCP). Post-ERCP pancreatitis (PEP) is caused mostly by postprocedural papillary edema and retention of pancreatic juice. We conducted a randomized controlled trial to determine whether placement of a temporary-type, pancreatic duct stent prevents PEP and to identify risk factors for PEP. We analyzed data from 426 consecutive patients who underwent ERCP-related procedures at 37 endoscopic units. The patients were assigned randomly to groups that received stents (S group, n = 213) or did not (nS group, n = 213). The stent used was temporary, 5F in diameter, 3 cm long, and straight with an unflanged inner end. The overall frequency of PEP was 11.3%. The frequencies of PEP in the S and nS groups were 7.9% and 15.2%, respectively; the lower incidence of PEP in the S group was statistically significant based on the full analysis set (P = .021), although there was no statistically significant differences in an intention-to-treat analysis (P = .076). There were significant differences in PEP incidence between groups in multivariate analysis for the following risk factors: pancreatography first, nonplacement of a pancreatic duct stent after ERCP, procedure time of 30 minutes or more, sampling of pancreatic tissue by any method, intraductal ultrasonography, and difficulty of cannulation (≥15 min). Patients with more than 3 risk factors had a significantly greater incidence of pancreatitis. Placement of a pancreatic duct stent reduces the incidence of PEP. Several risk factors are associated with PEP.


The inflammatory response to CPB: the role of leukocyte filtration.
Leukocyte activation is a significant component of the systemic inflammatory response to cardiopulmonary bypass (CPB). Various strategies have been developed aiming to reduce leukocyte activation and its deleterious effects on organ function after cardiac surgery. Leukocyte filtration aims to physically remove activated leukocytes from the circulation during CPB. The technique has been used since the mid-1990s but its efficacy in attenuating the effects of inflammatory response remains controversial. This article presents a review of published trials investigating the effects of leukocyte filtration on humans undergoing cardiac surgery.


Nutritional intervention improves the caloric and proteic ingestion of head and neck cancer patients under radiotherapy.
Malnutrition is commonly associated with head and neck cancer, due especially to anorexia, which is aggravated by radiotherapy. The objective of this study was to evaluate modifications to nutritional ingestion following three types of nutritional intervention. Sixty-four male out-patients (62.1 +/- 1.5 years) were divided into three groups: oral group, (n=32) that received an adapted oral diet; feeding tube group, (n=16) under home enteral nutrition via a nasoenteral feeding tube (6x/day); and supplement group, (n=16) with oral diet associated to oral alimentary supplement between meals (3x/day). The groups were homogeneous and counseled to maintain a caloric ingestion of 40 kcal/kg. The diet for the oral group was adapted to the age and to the side effects of radiotherapyThe nutritional state of the three groups was evaluated for the caloric-proteic ingestion, anthropometric indicators (body weight, body mass index, triceps skinfold thickness, midarm muscle area), laboratorial indicators (total proteins, albumin, hematocrit, hemoglobin and total lymphocytes count), The results showed that all of the groups presented an increase in the ingestion of calories and proteins (p < 0.001). The nutritional therapy support for patients with head and neck cancer under radiotherapy, whether exclusive oral diet, enteral through a feeding tube, or with alimentary supplement associated to an oral diet achieved a significant increase in the total caloric ingestion. It is recommended that programs be implemented-to improve the ingestion of foods among these patients.


Parathyroid hormone plasma level in untreated chronic renal failure and in hemodialyzed patients.
In 42 untreated patients at various stages of chronic renal failure, plasma level of parathyroid hormone was directly proportional to the degree of renal failure and inversely proportional to the serum calcium level. Plasma parathyroid hormone levels were frequently elevated in 21 patients undergoing regular dialysis treatment, in spite of normal levels of serum total calcium and magnesium. Serum-ionized calcium levels measured in dialyzed patients were usually reduced and inversely correlated with the creatinine levels. Parathyroid hormone levels were correlated with the creatinine levels, but the inverse relationship with ionized calcium was not significant.