Hydrogen sulfide protects against ischemic heart failure by inhibiting RIP1/RIP3/MLKL-mediated necroptosis.
The aim of the present study was to explore whether hydrogen sulfide (H2S) protects against ischemic heart failure (HF) by inhibiting the necroptosis pathway. Mice were randomized into Sham, myocardial infarction (MI), MI + propargylglycine (PAG) and MI + sodium hydrosulfide (NaHS) group, respectively. The MI model was induced by ligating the left anterior descending coronary artery. PAG was intraperitoneally administered at a dose of 50 mg/kg/day for 4 weeks, and NaHS at a dose of 4 mg/kg/day for the same period. At 4 weeks after MI, the following were observed: A significant decrease in the cardiac function, as evidenced by a decline in ejection fraction (EF) and fractional shortening (FS); an increase in plasma myocardial injury markers, such as creatine kinase-MB (CK-MB) and cardiac troponin I (cTNI); an increase in myocardial collagen content in the heart tissues; and a decrease of H2S level in plasma and heart tissues. Furthermore, the expression levels of necroptosis-related markers such as receptor interacting protein kinase 1 (RIP1), RIP3 and mixed lineage kinase domain-like protein (MLKL) were upregulated after MI. NaHS treatment increased H2S levels in plasma and heart tissues, preserving the cardiac function by increasing EF and FS, decreasing plasma CK-MB and cTNI and reducing collagen content. Additionally, NaHS treatment significantly downregulated the RIP1/RIP3/MLKL pathway. While, PAG treatment aggravated cardiac function by activated the RIP1/RIP3/MLKL pathway. Overall, the present study concluded that H2S protected against ischemic HF by inhibiting RIP1/RIP3/MLKL-mediated necroptosis which could be a potential target treatment for ischemic HF.


Ambulatory blood pressure monitoring in primary care.
The accurate assessment and appropriate management of blood pressure (BP) is critical for primary care physicians. Traditional office-based BP measurement has limitations that can be addressed, in part, through the use of ambulatory BP monitoring (ABPM). Because BP readings are provided at specific time intervals throughout a 24-hour period, ABPM represents a better picture of the normal fluctuations in BP levels associated with daily activities, including sleep. Blood pressure values obtained by 24-hour ABPM are a better predictor of cardiovascular risk than office-based BP measurements, and the technique can be used to discern white-coat hypertension and to evaluate masked, resistant, and pseudoresistant hypertension. It can also be helpful in the assessment of autonomic dysfunction and monitoring of a patient's response to antihypertensive therapy. Ambulatory BP monitoring is also being increasingly used in clinical trials that assess the antihypertensive effects of medications.


Features of Hepatocellular Carcinoma With Micro Hepatic Vein Invasion and their Correlation With Hepatitis B and C Virus.
Few studies have studied micro hepatic vein invasion in hepatocellular carcinoma (HCC). We explored the correlation between hepatic vein invasion and hepatitis B/C virus infection. Between April 2000 and February 2018, 869 patients underwent liver resection for HCC at a single center. The patients were divided into two groups: those with micro hepatic vein invasion (VV+) and those without (VV-). The clinical data, overall survival (OS) and correlations with the presence of hepatitis B and C viruses were investigated. There were 817 VV- patients and 43 VV+ patients. OS was 66.2 months for VV- patients and 9.9 months for VV+ patients (p=0.0010). VV+ patients had significantly higher levels of serum HBV DNA (p=0.016). HCC patients with micro hepatic vein invasion showed significantly shorter OS. A higher level of HBV DNA appears to be a risk factor for micro hepatic vein invasion.


A study of the histological basis of textural analysis.
In an attempt to quantitate histological structure by textural analysis, the characters of a stained microscopical field were recorded as a frequency polygon of the relative areas defined by successive increments of optical density: this is known as the optical density/area (OD/A) profile. In a study of lymph-nodes in Hodgkin's disease and of carcinoma of the female breast, each stained tissue section was found to have an OD/A profile of characteristic shape: moreover, in each of the lesions studied it was shown that the shape of the profile could be replicated by summing the profiles of each constituent cell type and intercellular matrix in proportions determined by differential cell counts and direct measurement of the degree of cell packing in the tissue. In an investigation of the influence of specimen preparation on OD/A profile, it was shown that density of staining and section thickness were important variables. Using the density of staining of tissue lymphocytes as an internal standard, a simple method was developed of compensating for differences in the density of Mayer's haemalum staining greater than those met with in practice. Attempts to compensate for intentionally large differences in section thickness were much less successful, but this was considered to be relatively unimportant since, in practice, the variation in thickness of sections cut on a modern microtome by a competent microtomist had been shown to be slight and to have a negligible effect on the OD/A profile.


Ecarin modified rotational thrombelastometry: a point-of-care applicable alternative to monitor the direct thrombin inhibitor argatroban.
Adequate monitoring of the effect of the direct thrombin inhibitor argatroban may facilitate individualized dosing and perioperative management of anticoagulation. Ecarin Clotting Time is proposed for this purpose, but has the major disadvantage of limited availability. There is a point-of-care applicable ecarin-activated test modification for rotational thrombelastometry (ROTEM®) which is sensitive to direct thrombin inhibitors. The aim of the study was to evaluate the correlation between argatroban concentration and this ecarin modified thrombelastometry (EMT). In this in vitro experiment, blood drawn from healthy volunteers was spiked with argatroban at clinically relevant concentrations and analyzed with ROTEM® using EMT. The main endpoint was the clotting time (CT). EMT-CT was prolonged with increasing argatroban concentrations (from 83.3 ± 6.7 s without argatroban to 743.5 ± 138.2 s at 2 μg/ml argatroban). The correlation between argatroban concentration and EMT-CT was high (r = 0.94) and statistically significant (p < 0.01). These promising preclinical results mandate further clinical research to determine an EMT-CT target range regarding the clinical outcomes of thrombosis and bleeding.


In the footsteps of history: the bees of the genus Hylaeus Fabricius (Hymenoptera, Apoidea: Colletidae) collected by V.I. Roborovsky and P.K. Kozlov in Northwest China (1895-1926).
An annotated list of 19 species of Hylaeus collected by the famous Russian explorers and travellers V.I. Roborovsky and P.K. Kozlov in Northwest China (1895-1926) is given. Hylaeus (Hylaeus) roborovskyi Proshchalykin Dathe, sp. nov. is described as new from Xinjiang Uygur Autonomous Region. The following eight known species are newly recorded from China: Hylaeus angustatus (Schenck, 1861), H. arenarius Morawitz, 1876, H. breviceps Morawitz, 1876, H. communis Nylander, 1852, H. fedtschenkoi (Cockerell, 1906), H. pallidicornis Morawitz, 1876, H. pesenkoi Proshchalykin Dathe, 2016, and H. vulgaris Morawitz, 1876, increasing the number of species reported from the region to 48. New synonymy is established for Hylaeus tsingtauensis (Strand, 1915) = H. montivagus Dathe, 1986, syn. nov.


Multi-Scale Modeling of Head Kinematics and Brain Tissue Response to Blast Exposure.
Injuries resulting from blast exposure have been increasingly prevalent in recent conflicts, with a particular focus on the risk of head injury. In the current study, a multibody model (GEBOD) was used to investigate the gross kinematics resulting from blast exposure, including longer duration events such as the fall and ground impact. Additionally, detailed planar head models, in the sagittal and transverse planes, were used to model the primary blast wave interaction with the head, and resulting tissue response. For severe blast load cases (scaled distance less than 2), the translational head accelerations during primary blast were found to increase as the height-of-burst (HOB) was lowered, while the HOB was found to have no effect for cases with scaled distance greater than 2. The HOB was found to affect both the magnitude and direction of rotational accelerations, with increasing magnitudes as the HOB deviated from the height of the head. The choice of ground contact stiffness was found to greatly affect the predicted head accelerations during ground impact. For a medium soil ground material, the kinematics during ground impact were greater for scaled distances exceeding 1.5, below which the primary blast produced greater kinematic head response.


Splenic suppressor of cytokine signaling 3 transgene expression affects T cell responses and prevents development of collagen-induced arthritis.
Members of the suppressor of cytokine signaling (SOCS) family are key negative intracellular regulators of cytokine and growth factor responses, including those that regulate immune responses in autoimmune disorders, such as rheumatoid arthritis (RA). The aim of this study was to investigate modulation of T cell immunity for the treatment of experimental arthritis, via enhanced expression of SOCS-3 in splenic antigen-presenting cells (APCs) obtained after intravenous injection of adenovirus encoding SOCS-3. DBA/1 mice were immunized with type II collagen, and adenovirus vectors were administered by intravenous injection before the clinical onset of collagen-induced arthritis (CIA). Splenic cellular responses were analyzed by measuring cytokine production, using Luminex multi-analyte technology. Th cell populations were analyzed by flow cytometry. Systemic delivery of adenovirus encoding SOCS-3 resulted in enhanced transgene expression in splenic APCs, which led to decreased production of interleukin-23 (IL-23), IL-6, and tumor necrosis factor alpha, but significantly higher production of antiinflammatory IL-10, by these cells. Fluorescence-activated cell sorting analysis showed increased numbers of splenic CD4+ T cells after SOCS-3 treatment. In the presence of SOCS-3-transduced APCs, however, purified splenic CD3+ T cells showed reduced antigen-specific proliferation and a significant reduction in the production of interferon-gamma (-43%), IL-4 (-41%), and IL-17 (-70%). Interestingly, the altered splenic cellular responses were accompanied by a protective effect on CIA development, and histologic analysis of knee joints showed reduced joint inflammation and connective tissue destruction. This study demonstrates effective prevention of CIA after intravenously induced overexpression of SOCS-3; this is probably caused by the generation of tolerogenic APCs, which have an inhibitory effect on Th1, Th2, and especially, Th17 cell activity.


[Diagnostic problems of spinal tumors in childhood and adolescence].
In evaluation of the clinical-neurological symptoms of 59 children and juveniles with spinal space occupations, 43 of whom were operated on, the differential-diagnostic particularities especially with respect to the early symptoms are discussed. On the basis of representations of individual cases, the importance of metrizamide myelography and spinal computer tomography for the pre-operative diagnosis is pointed out.


Acupuncture methods for insomnia disorder in the elderly: protocol for a systematic review and network meta-analysis.
Insomnia disorder remains one of the most common sleep disorders in the elderly, with high prevalence and substantial consequences for patients' general health. Despite that increasing clinical trials have indicated that acupuncture seems to be effective for insomnia disorder in the elderly, comparative efficacy and safety of different acupuncture methods for elderly individuals with insomnia disorder has been unclear. Therefore, this protocol outlined a plan to evaluate and rank the efficacy and safety of various acupuncture approaches for insomnia disorder in the elderly. A systematic search of 8 bibliographic databases will be conducted from their inception to 18 June 2023, including Cochrane Library, MEDLINE (via PubMed), Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, and Chinese Biomedical Literature Database (CBM). Randomized controlled trials investigating acupuncture methods for insomnia disorder in the elderly, published in English or Chinese will be included. The primary outcome is sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI). Two reviewers will independently perform study selection, data extraction and risk assessment of bias. The quality of included literatures will be appraised using Cochrane risk-of-bias tool (ROB 2.0). ADDIS (Aggregate Data Drug Information System) V.1.16.8 will be used to conduct Bayesian network meta-analysis. The quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation System (GRADE). In this study, the results will provide credible evidence to assess the efficacy and safety of acupuncture therapies for elderly patients with insomnia disorder, assisting patients, physicians and clinical research investigators to select the most appropriate acupuncture method. The protocol has been registered at OSF ( https://osf.io/3kjpq/ ) with a registration number https://doi.org/10.17605/OSF.IO/3KJPQ .


Constitutive JNK activation in NIH 3T3 fibroblasts induces a partially transformed phenotype.
The c-Jun N-terminal kinases (JNKs) (also known as stress-activated protein kinases or SAPKs), members of the mitogen-activated protein kinase (MAPK) family, regulate gene expression in response to a variety of physiological and unphysiological stimuli. Gene knockout experiments and the use of dominant interfering mutants have pointed to a role for JNKs in the processes of cell differentiation and survival as well as oncogenic transformation. Direct analysis of the transforming potential of JNKs has been hampered so far by the lack of constitutively active forms of these kinases. Recently, such mutants have become available by fusion of the MAPK with its direct upstream activator kinase. We have generated a constitutively active SAPK beta-MKK7 hybrid protein and, using this constitutively active kinase, we are able to demonstrate the transforming potential of activated JNK, which is weaker than that of classical oncogenes such as Ras or Raf. The inducible expression of SAPK beta-MKK7 caused morphological transformation of NIH 3T3 fibroblasts. Additionally, these cells formed small foci of transformed cells and grew anchorage-independent in soft agar. Furthermore, similar to oncogenic Ras and Raf, the expression of activated SAPK beta resulted in the disassembly of F-actin stress fibers. Our data suggest that constitutive JNK activation elicits major aspects of cellular transformation but is unable to induce the complete set of changes which are required to establish the fully transformed phenotype.


An epidemic of hepatitis A in an institution for young children.
A common-source epidemic of hepatitis A occurred in an Athenian institution boarding 38 children (mean age 4.8 years). All children were examined, and blood was drawn from each at the onset of the study and repeatedly during the next three months. Only one child (2.6%) was initially immune to hepatitis A virus as a result of prior infection. The attack rate (62.2%) and the ratio of icteric to anicteric cases (1:1.3) were high despite the administration of immunoglobulin (IG). Assays for anti-HAV IgM and a rising titer of anti-HAV IgG identified 19 (82.6%) and 22 (95.7%) of the 23 hepatitis A infections, respectively. One case (4.3%) was detected only by the presence of hepatitis A virus antigen and hepatitis A virus RNA in a fecal specimen, but these assays were otherwise marginally useful in this study. Nevertheless, the use of all available tests for the detection of hepatitis A virus is mandatory for the most accurate estimation of an epidemic of hepatitis A. Prompt administration of immunoglobulin had no effect on the number of clinical cases that were in the late incubation period, but it may have diminished the clinical expression of the infection and thus made diagnosis of infection more difficult.


Non-painful sensory phenomena after spinal cord injury.
Non-painful sensory phenomena or "phantom" sensations are common after spinal cord injury. However, the physiological mechanisms responsible for these sensations are poorly understood. The aim of this study, therefore, was to document in a prospective fashion the time course, prevalence, and features of non-painful sensory phenomena after spinal cord injury, and to determine whether there was a relation between the presence of these sensations and completeness, level of injury, and type of spinal cord injury. Patients admitted to an acute spinal injuries unit were interviewed after admission and at several time points over a 2 year period to determine the presence and characteristics of non-painful sensations. Sensations were divided into simple and complex, with complex referring to sensations that incorporated a sensation of volume, length, posture, or movement. The present study showed that the large majority (90%) of patients experience either type of sensation and most complex sensations (60%) are first experienced within 24 hours after the injury. Complex sensations were more common in those patients who had complete spinal cord injuries. The presence of either type of sensation did not seem to be related to the level of injury or the type of injury (cord syndrome). A relatively small proportion (22%) of patients reported that the postural sensations were related to their position at the time of injury and sensations were more commonly related to a familiar, comfortable, or often used position before the spinal cord injury. Complex sensations such as postural illusions seem to be due to functional changes in the CNS that may occur almost immediately after spinal cord injury. These sensations may be related to a strong sensory memory "imprint" that has been established before injury.


Factors influencing mortality in spontaneous gastric tumour perforations.
Spontaneous perforation of gastric cancer is a serious complication with a very high incidence of mortality. In order to evaluate the prognostic factors influencing mortality in patients with gastric tumour perforations and to clarify the optimal surgical treatment, the records of patients at one centre during a 5-year period were evaluated retrospectively. Between 1995 and 2000, 14 patients with perforated gastric cancer were operated on in the Emergency Surgical Unit of a Turkish Hospital. This figure represents 3% of all the patients with gastric cancer who were treated during the same period. The hospital mortality was 36% in patients with perforations. The duration of symptoms suggesting perforation and the presence of pre-operative shock were predictive factors of mortality. It was concluded that those patients with pre-operative shock and delayed diagnosis should be treated with extra caution to decrease mortality. Perforation and peritonitis must be treated initially and elective radical surgery delayed.


Management of Postoperative Discitis with Debridement and Novel Technique of Local Antibiotic Instillation: Functional Outcomes from a Resource-Limited Setting.
Patients in low- and middle-income countries (LMICs) have substantial treatment abandonment and non-adherence with outpatient oral medications. This work sought to investigate outcomes of postoperative discitis treated with debridement and a novel technique focused on reducing outpatient antibiotic requirement in an LMIC setting. This study, conducted and reported following STROBE guidelines, reviewed outcomes of all patients with postoperative discitis who had been debrided by 1 neurosurgeon in a resource-limited setting during 2008-2020. Patients had undergone single-level L4-L5 or L5-S1 discectomy elsewhere, later developing magnetic resonance imaging-confirmed discitis. After non-response or deterioration following intravenous antibiotics, patients underwent early debridement, followed by in-patient antibiotic instillation into disc space for 2 weeks via drain. Study outcomes were modified Kirkaldy-Willis Grade, Japan Orthopaedic Association (JOA) score, and visual analog scale (VAS) score, all assessed at 1 year. Twelve patients were included, 10 male and 2 female, with median age of 46 (IQR 3.5) years. Debridement was done after median 82.5 (IQR 35) days and took median time of 105 (IQR 17.5) minutes. VAS scores (mean ± SD) decreased from 9.25 ± 0.75 preoperatively to 0.67 ± 0.89 1 year postoperatively (mean difference 8.58, 95% CI 8.01-9.15, P < 0.001). JOA scores (mean ± SD) improved from 4.5 ± 2.94 to 26.42 ± 1.31 1 year postoperatively (mean difference 21.92, 95% CI 20.57-23.26, P < 0.001). Kirkaldy-Willis grade was excellent in 6 (50%) patients, good in 5 (41.7%), and fair in 1 (8.3%). Patients became ambulatory within 2 weeks, with no major complications during 4.15 (IQR 3.45) years of median follow-up. In LMICs, patients with medically refractory postoperative discitis potentially have good outcomes after debridement plus 2-week local antibiotic instillation.


Different effects of opioid and cannabinoid receptor agonists on C-fiber-induced extracellular signal-regulated kinase activation in dorsal horn neurons in normal and spinal nerve-ligated rats.
Nerve injury results in neuropathic pain, a debilitating pain condition. Whereas cannabinoids are consistently shown to attenuate neuropathic pain, the efficacy of opioids is highly controversial. Molecular mechanisms underlying analgesic effects of opioids and cannabinoids are not fully understood. We have shown that the signaling molecule ERK (extracellular signal-regulated kinase) is activated by C-fiber stimulation in dorsal horn neurons and contributes to pain sensitization. In this study, we examined whether opioids and cannabinoids can affect C-fiber-induced ERK phosphorylation (pERK) in dorsal horn neurons in spinal cord slices from normal and spinal nerve-ligated rats. In normal control spinal slices, capsaicin induced a drastic pERK expression in superficial dorsal horn neurons, which was suppressed by morphine (10 microM), the selective mu-opioid receptor agonist DAMGO [[d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (1 microM)], and the selective CB1 receptor ACEA agonist [arachidonyl-2'-chloroethylamide (5 microM)]. One week after spinal nerve ligation when neuropathic pain is fully developed, capsaicin induced less pERK expression in the injured L(5)-spinal segment. This pERK induction was not suppressed by morphine (10 microM) and DAMGO (1 microM) but was enhanced by high concentration of DAMGO (5 microM). In contrast, ACEA (10 microM) was still very effective in inhibiting capsaicin-induced pERK expression. In the adjacent L(4) spinal segment, both DAMGO and ACEA significantly suppressed pERK induction by capsaicin. These results indicate that, after nerve injury, opioids lose their capability to suppress C-fiber-induced spinal neuron activation in the injured L(5) but not in the intact L(4) spinal segment, whereas cannabinoids still maintain their efficacy.


The Oncogenic Relevance of miR-17-92 Cluster and Its Paralogous miR-106b-25 and miR-106a-363 Clusters in Brain Tumors.
The fundamental function of ribonucleic acids is to transfer genetic information from DNA to protein during translation process, however, this is not the only way connecting active RNA sequences with essential biological processes. Up until now, many RNA subclasses of different size, structure, and biological function were identified. Among them, there are non-coding single-stranded microRNAs (miRNAs). This subclass comprises RNAs of 19-25 nucleotides in length that modulate the activity of well-defined coding RNAs and play a crucial role in many physiological and pathological processes. miRNA genes are located both in exons, introns, and also within non-translated regions. Several miRNAs that are transcribed from the adjacent miRNA genes are called cluster. One of the largest ones is miR-17-92 cluster known as OncomiR-1 due to its strong link to oncogenesis. Six miRNAs from the OncomiR-1 have been shown to play important roles in various physiological cellular processes but also through inhibition of cell death in many cancer-relevant processes. Due to the origin and similarity of the sequence, miR-17-92 cluster and paralogs, miR-106b-25 and miR-106a-363 clusters were defined. Here we discuss the oncogenic function of those miRNA subgroups found in many types of cancers, including brain tumors.


A Previously Unknown Path to Corpuscularism in the Seventeenth Century: Santorio's Marginalia to the Commentaria in Primam Fen Primi Libri Canonis Avicennae (1625).
This paper presents some of Santorio's marginalia to his Commentaria in primam fen primi libri Canonis Avicennae (Venice, 1625), which I identified in the Sloane Collection of the British Library in 2016, as well as the evidence for their authorship. The name of the Venetian physician Santorio Santori (1561-1636) is linked with the introduction of quantification in medicine and with the invention of precision instruments that, displayed for the first time in this work, laid down the foundations for what we today understand as evidence-based medicine. But Santorio's monumentale opus also contains evidence of many quantified experiments and displays his ideas on mixtures, structure of matter and corpuscles, which are in many cases clarified and completed by the new marginalia. These ideas testify to an early interest in chemistry within the Medical School of Padua which predates both Galileo and Sennert and which has hitherto been unknown.


Effect of post-ethanol extraction sorghum silage as a forage source in growing and finishing diets on steer performance, carcass characteristics, and nutrient digestibility.
Two experiments evaluated the use of post-ethanol extraction sorghum silage as an alternative forage source in feedlot diets. Seventy-two crossbred steers (397 kg [SD 23]) were used to evaluate growth and carcass characteristics. Steers were blocked by BW into pens of 6 steers and randomly assigned to growing diets containing 40% (DM basis) sorghum silage (SS; 57.6% NDF) or grass hay (CON; 63.3% NDF) for 56 d ( = 6 pens per treatment). Within each treatment, steers transitioned to dry-rolled corn-based finishing diets (fed for 56 d) containing 6% effective NDF contributed by the forage source, resulting in forage inclusions of 16% for SS and 13.1% for CON, where forage replaced corn. A subsample of steers ( = 12 per treatment) housed in pens equipped with GrowSafe bunks were used for determination of growing phase diet total tract digestibility. From d 28 to 42, steers received titanium dioxide at approximately 10 g∙steer∙d, and fecal samples were collected on d 41 and 42. Fecal and total mixed ration samples were dried and ground for analysis of DM, OM, NDF, ADF, CP, ether extract (EE), and starch. Data were analyzed with the MIXED procedure of SAS, with fixed effects of treatment and block for performance and carcass data or treatment for digestibility data; significance was determined at ≤ 0.05 and tendencies at ≤ 0.10. Growing phase DMI and ADG did not differ due to treatment ( ≥ 0.19); however, SS-fed steers had improved G:F compared with CON-fed steers ( = 0.04). Finishing period ADG and G:F did not differ ( ≥ 0.15) between treatments, despite SS-fed steers having lesser ( = 0.008) DMI than CON-fed steers. No differences in DMI, ADG, or G:F over the whole trial were noted between treatments ( ≥ 0.12) nor were any carcass traits affected ( ≥ 0.23). During the digestibility assessment period, DMI was less ( = 0.003) in SS-fed steers. Growing phase total tract apparent digestibility of DM and starch did not differ ( ≥ 0.19) due to treatment; however, OM digestibility tended to be greater ( = 0.09) in SS-fed steers. Steers fed SS had greater ( ≤ 0.03) digestibility of EE, CP, NDF, and hemicellulose than CON-fed steers. However, CON-fed steers had greater ( < 0.0001) ADF digestibility than SS-fed steers. These data suggest that postextraction sorghum silage can be effectively used in feedlot diets as an alternative forage source.


Optimizing therapy of seizures in neurosurgery.
The use of antiepileptic drugs (AEDs) in the neurosurgical setting has a number of implications, including their possible role in the prevention of seizures after acute cerebral insults or brain tumors and the potential for toxicity and interactions when these agents are administered in association with radiotherapy or chemotherapy. This review discusses these controversial issues and draws the following conclusions. 1) AEDs should be prescribed on a short-term basis to prevent seizures occurring within the first week after a cerebral insult (trauma, neurosurgical procedure) but are ineffective to avoid true post-traumatic epilepsy or first seizures in patients with primary or secondary cerebral neoplasms. 2) The use of phenytoin and, to a lesser extent, phenobarbital and carbamazepine during cranial irradiation is associated with an increased risk for severe, potentially fatal, mucocutaneous reactions. In this context, new AEDs with a very low potential for allergic cutaneous reactions should be preferred. 3) Enzyme-inducing AEDs, such as phenytoin, phenobarbital, and carbamazepine, may increase the clearance and reduce the clinical efficacy of corticosteroids and anticancer agents that are also metabolized by the cytochrome P450 system. The newly developed AEDs that are devoid of hepatic metabolism, such as levetiracetam and gabapentin, are now recommended because of good results in preliminary studies and because they do not show interactions with anticancer agents.


Monitoring architectural heritage by wireless sensors networks: San Gimignano--a case study.
This paper describes a wireless sensor network (WSN) used to monitor the health state of architectural heritage in real-time. The WSN has been deployed and tested on the "Rognosa" tower in the medieval village of San Gimignano, Tuscany, Italy. This technology, being non-invasive, mimetic, and long lasting, is particularly well suited for long term monitoring and on-line diagnosis of the conservation state of heritage buildings. The proposed monitoring system comprises radio-equipped nodes linked to suitable sensors capable of monitoring crucial parameters like: temperature, humidity, masonry cracks, pouring rain, and visual light. The access to data is granted by a user interface for remote control. The WSN can autonomously send remote alarms when predefined thresholds are reached.


Resilience and quality of life in 161 living kidney donors before nephrectomy and in the aftermath of donation: a naturalistic single center study.
Due to the shortage of cadaveric organs, living kidney donation has begun to serve as the most crucial organ pool. Transplant centers have a legitimate interest in expanding the pool of donors. A psychosocial evaluation is established in transplantation centers to prevent donors from possible emotional harm in the aftermath of donation. We explored if the resilience questionnaire is an appropriate measure of the mental stability. To standardize procedures of psychosocial evaluation and to optimize donor recruitment, we present our evaluation protocol and analyze the causes of exclusion from donation. In a naturalistic design, we compared resilience and quality of life in eligible and excluded donors at the time point of donation. Potential living kidney donors (N = 161) participated in the obligatory psychosomatic evaluation. Quality of life (World Health Organization Quality of Life, WHOQOL-Bref) and resilience (Resilience Scale, RS-12) were measured. Three months after nephrectomy donors quality of life was screened in a follow-up. In the evaluation interview donors were classified as eligible (n = 142) or excluded (n = 12). Nonrelated donors (n = 3) were excluded from donation significantly more often (p < .011). Eligible donors (M = 78.42, SD = 10.19) had higher values for resilience than excluded donors (M = 72.7, SD = 8.18, p < .04), who showed values comparable to the norm. In all domains of quality of life, eligible donors had significantly higher values than healthy normals (p < .001). After donation health-related quality of life decreased, but was comparable to the norm. A regression analysis showed that resilience was a significant predictor for all dimensions of quality of life before donation (R(2) = 10.2-24.6 %). Post-donation quality of life was significantly correlated with pre-donation resilience scores (p < .05). The resilience score predicts high mental quality of life before and after donation. Therefor it can be implemented as a self-rating instrument to further objectify donor's mental stability. Despite the stressful life event of donation, donor candidates presented high resilience and high levels of quality of life. Therefor our findings support health care providers` intentions to improve living donation. In the group of excluded donors nonrelated persons were overrepresented. Guidelines for the admission of nonrelated donors are currently unclear and need to be optimized.


[Diffuse connective tissue diseases (DCTD)--a review].
The diffuse connective tissue diseases constitute a group of inflammatory diseases with the potential of involvement of many organ systems. The etiopathogenesis is thought to be multifactorial, involving the interaction between particular genetic background and exogenous agents. Recently theories regarding inherited defects in the clearing of immune complexes have been put forward. Serological markers are important diagnostic tools in many of these diseases and emphasize the role of autoimmunity. Epidemiological studies have demonstrated an increase in incidence in some of these diseases and because of selection bias many epidemiological studies may overestimate the severity of these diseases. Therapy aims at modulating and suppressing inflammation. A step towards more directed immune modulation is the use of cyclosporin A and monoclonal antibodies against various surface antigens and mediators in inflammation.


Non-additive Effects in Genomic Selection.
In the last decade, genomic selection has become a standard in the genetic evaluation of livestock populations. However, most procedures for the implementation of genomic selection only consider the additive effects associated with SNP (Single Nucleotide Polymorphism) markers used to calculate the prediction of the breeding values of candidates for selection. Nevertheless, the availability of estimates of non-additive effects is of interest because: (i) they contribute to an increase in the accuracy of the prediction of breeding values and the genetic response; (ii) they allow the definition of mate allocation procedures between candidates for selection; and (iii) they can be used to enhance non-additive genetic variation through the definition of appropriate crossbreeding or purebred breeding schemes. This study presents a review of methods for the incorporation of non-additive genetic effects into genomic selection procedures and their potential applications in the prediction of future performance, mate allocation, crossbreeding, and purebred selection. The work concludes with a brief outline of some ideas for future lines of that may help the standard inclusion of non-additive effects in genomic selection.


Comprehensive Analysis of Phytochemical Constituents and Ethnopharmacological Investigation of Genus Datura.
The genus Datura comprises wild shrub plants that belong to the Solanaceae family. Naturally, they possess both medicinal and poisonous properties due to the presence of many biologically active phytochemical constituents. Traditionally, Datura had been used for mystic and religious purposes, as a natural drug to treat asthma, pain, gout, boils, abscesses, and wounds, and as psychoactive infusions and fumitories. Different Datura species exhibit diverse ethnopharmacological activities against different diseases, and many ancient and traditional cultures have used various forms of Datura to treat ailments and to prevent many diseases. In this article, we comprehensively summarize various phytochemical constituents isolated from Datura, their pharmacological properties against different diseases, parts of the plants used as traditional therapeutic agents, regions where they are located, and botanical descriptions of different Datura species. The ethnopharmacological properties of Datura may provide new insights for discovery and development of natural drugs. Further research is needed for the investigation of mechanisms of action and to develop safety profiles of the phytochemical constituents isolated from Datura species.


Lung Imaging Reveals Stroke-Induced Impairment in Pulmonary Intravascular Neutrophil Function, a Response Exacerbated with Aging.
In stroke patients, infection is a significant contributor to morbidity and mortality. Moreover, older stroke patients show an increased risk of developing stroke-associated infection, although the mechanisms underlying this increased susceptibility to infection are unknown. In this study, using an experimental mouse model of ischemic stroke, we showed that older (12-15 mo of age) mice had elevated lung bacterial infection and inflammatory damage after stroke when compared with young (8-10 wk of age) counterparts, despite undergoing the same degree of brain injury. Intravital microscopy of the lung microvasculature revealed that in younger mice, stroke promoted neutrophil arrest in pulmonary microvessels, but this response was not seen in older poststroke mice. In addition, bacterial phagocytosis by neutrophils in the lung microvasculature was reduced by both aging and stroke, such that neutrophils in aged poststroke mice showed the greatest impairment in this function. Analysis of neutrophil migration in vitro and in the cremaster muscle demonstrated that stroke alone did not negatively impact neutrophil migration, but that the combination of increased age and stroke led to reduced effectiveness of neutrophil chemotaxis. Transcriptomic analysis of pulmonary neutrophils using RNA sequencing identified 79 genes that were selectively altered in the context of combined aging and stroke, and they were associated with pathways that control neutrophil chemotaxis. Taken together, the findings of this study show that stroke in older animals results in worsening of neutrophil antibacterial responses and changes in neutrophil gene expression that have the potential to underpin elevated risk of stroke-associated infection in the context of increased age.


Differential effect of body mass index on the incidence of diabetes and diabetic retinopathy in two Asian populations.
To examine the association of body mass index (BMI) with the incidence of diabetes mellitus (DM) and diabetic retinopathy (DR) in Asians. We analysed data from 4101 adults (Malay, n = 1901 and Indian, n = 2200) who participated in the baseline (2004-2009) and 6-year follow-up (2011-2015) of two independent population-based studies with similar methodology in Singapore. BMI was categorised into normal (<25 kg/m2), overweight (25-29.9 kg/m2) and obese (≥30 kg/m2). DM was diagnosed as random plasma glucose ≥200 mg/dL, HbA1c ≥6.5% or self-reported physician diagnosed DM. DR was assessed from retinal photographs graded using a standard protocol. The associations of baseline BMI with incident DM and DR was examined using multivariable poisson regression models adjusting for potential confounders including duration of DM, family history of DM and HbA1c. The incidence of DM was 12.8% and among 1586 participants with DM, the incidence of DR was 17.6% over a median follow-up period of 6.2 years. Compared to those with BMI < 25, the relative risk (95% confidence interval) of incident DM was 1.77 (1.36-2.29) for overweight and 2.01 (1.50-2.71) for obese (p trend < 0.001). Relative risk of DR was 0.80 (0.59-1.09) for overweight and 0.60 (0.39-0.92) for obese (p trend = 0.02). In analyses stratified by ethnicity, similar pattern of associations with DM and DR were observed in both ethnicities. Our results suggest that, overweight and obesity increased the 6-year risk of DM but decreased the 6-year risk of DR in these Asian populations.


Experiences of a nutrition intervention-A qualitative study within a randomised controlled trial in men undergoing radiotherapy for prostate cancer.
Men with prostate cancer undergoing radiotherapy may experience acute and late bowel symptoms. Nutrition interventions have shown some benefits, however, adherence tends to decline over time. Qualitative studies, carried out after an intervention, are important to help explain trial results. The aim of the present study was to explore patient experience of participating in a nutrition intervention in a randomised controlled trial, with a focus on facilitators and barriers to adherence. Semistructured interviews were conducted with 15 men with prostate cancer recruited from a randomised controlled trial on a nutrition intervention during radiotherapy. Interviews were analysed with content analysis with an inductive approach. The informants were motivated to make dietary changes to avoid bowel symptoms. Social support, a feeling of contributing to the greater good, prior knowledge, dietary information and a small need for behaviour change facilitated adherence. Feeling limited, wanting to decide for themselves, the timing of the intervention, unmet expectations of dietary advice and loss of motivation, were described as barriers for adherence. Future nutrition intervention trials may benefit from involving significant others to a greater degree, as well as offering pre-set recipes and strategies to manage social events, and more sessions with the dietitian for patients in need of more support. Tailored interventions based on the individual's preferences, context and prior knowledge about food may further facilitate adherence.


Reticulocyte 15-lipoxygenase-I is important in acetylcholine-induced endothelium-dependent vasorelaxation in rabbit aorta.
Aortic 15-lipoxygenase (15-LO) metabolizes arachidonic acid (AA) to 15-hydroperoxyeicosatetraenoic acid, which is then converted to the vasodilators 15-hydroxy-11,12-epoxyeicosatrienoic acid and 11,12,15-trihydroxyeicosatrienoic acid. These metabolites contribute to endothelium-dependent relaxations of rabbit aorta to AA and acetylcholine. We investigated the identity of rabbit aortic 15-LO and studied its importance in the regulation of vascular tone. RT-PCR using 12-lipoxygenase/15-LO specific primers resulted in a 572-bp product with a sequence identical to 15-LO-I from rabbit aorta. A RT-PCR/restriction digest strategy excluded expression of 12-lipoxygenase. Immunoblotting revealed 15-LO-I expression in rabbit endothelial and smooth muscle cells. Aortic homogenates and cytosolic fractions metabolize AA to 15(S)-hydroxyeicosatetraenoic acid and linoleic acid to 13(S)-hydroxyoctadecadienoic acid. This activity was blocked by LO inhibitors. The kinetic characteristics (Michaelis constant of aortic 15-LO is 2.2+/-0.3 micromol/L for AA and 23.5+/-3.3 micromol/L for linoleic acid) of aortic 15-LO were similar to those of the purified 15-LO-I. An antisense oligonucleotide inhibited 15-LO-I expression in rabbit aorta. Indomethacin and nitro-L-arginine-resistant relaxations to acetylcholine were inhibited by 15-LO-I antisense oligonucleotide but not by the scrambled oligonucleotide. 15-LO-I is expressed in rabbit aortic endothelium and is important in endothelium-dependent regulation of vascular tone.


Clinical feasibility and effectiveness of bedside peripherally inserted central catheter using portable digital radiography for patients in an intensive care unit: A single-center experience.
The aim of this study was to evaluate the clinical feasibility and effectiveness of bedside peripherally inserted central catheter (PICC) using portable digital radiography (DR) in intensive care unit (ICU) patients.Sixty-five ICU patients who underwent PICC were enrolled in this study between May 2016 and May 2017. Of these 65 patients, 45 (69.2%) underwent the procedures bedside in ICU using portable DR, and 20 (30.8%) underwent the procedures at the intervention clinic, both performed by a single interventional radiologist. We retrospectively reviewed electronic medical records for clinical presentation, total procedural time, total radiation dose, total patient transfer time, and clinical outcomes. We performed an independent t test to compare the clinical effectiveness between the 2 groups.The technical and clinical success rates were 100% in both groups, and there were no procedure-related complications. The total radiation dose of bedside PICC at ICU was significantly lower than that of conventional PICC at the intervention clinic (557.9 mGy*cm ± 209.2 vs 985.2 mGy*cm ± 547.6, P < .001). The total procedure time was significantly different between the bedside and conventional PICC groups (26.8 minutes ± 3.9 vs 24.1 minutes ± 5.55, P = .028). The average patient transfer time to the intervention clinic was 26.6 minutes ± 9.8.Bedside PICC using portable DR is a safe and effective procedure option to manage ICU patients in daily clinical practice.


Characterization of a Cry1Ac-receptor alkaline phosphatase in susceptible and resistant Heliothis virescens larvae.
We reported previously a direct correlation between reduced soybean agglutinin binding to 63- and 68-kDa midgut glycoproteins and resistance to Cry1Ac toxin from Bacillus thuringiensis in the tobacco budworm (Heliothis virescens). In the present work we describe the identification of the 68-kDa glycoprotein as a membrane-bound form of alkaline phosphatase we term HvALP. Lectin blot analysis of HvALP revealed the existence of N-linked oligosaccharides containing terminal N-acetylgalactosamine required for [125I]Cry1Ac binding in ligand blots. Based on immunoblotting and alkaline phosphatase activity detection, reduced soybean agglutinin binding to HvALP from Cry1Ac resistant larvae of the H. virescens YHD2 strain was attributable to reduced amounts of HvALP in resistant larvae. Quantification of specific alkaline phosphatase activity in brush border membrane proteins from susceptible (YDK and F1 generation from backcrosses) and YHD2 H. virescens larvae confirmed the observation of reduced HvALP levels. We propose HvALP as a Cry1Ac binding protein that is present at reduced levels in brush border membrane vesicles from YHD2 larvae.


Site-specific integration by adeno-associated virus is directed by a cellular DNA sequence.
Different regions of an 8.2-kb cloned DNA segment containing the target for adeno-associated virus (AAV) integration in human chromosome 19q13-3-qter (AAVS1 locus) were subcloned in an Epstein-Barr virus-based shuttle vector and propagated as episomes in a derivative of the 293 human embryonic kidney cell line. Preferential recombination with an infecting AAV genome was assessed by measuring the frequency of recombinants among the shuttle vectors recovered in Escherichia coli. The signals which direct recombination with the AAV genome were localized to a 510-nt region at the 5' end of the 8.2-kb AAVS1 DNA. Hence, the results indicate that site-specific integration of AAV is directed by a specific DNA sequence on human chromosome 19. An unusual degree of DNA heterogeneity in the recovered vector was also associated with the 510 nt at the 5' end of AAVS1 DNA, suggesting that the AAV chromosomal integration locus may be involved in genomic instability.


Childhood trauma and type D personality: The endocrine and cardiovascular effects on stress reactivity.
Both exaggerated and blunted cardiovascular stress reactions are associated with health problems. Moreover, early life experiences and personality traits affect stress responses. Regarding the childhood traumas and type D personality, this study aimed to compare the endocrine and cardiovascular reactions against acute laboratory stress. Results showed that the simultaneous existence of childhood traumatic experiences and type D personality leads to exaggerated stress reactivity, while each factor results in a blunted cardiovascular response. Although the cardiovascular responses are dampened in type D personality people, their endocrine reactions are exaggerated. The underlying mechanisms of blunted cardiovascular reactivity differ between childhood trauma and type D personality groups.


Simultaneous density and magnetic field fluctuation measurements by far-infrared interferometry and polarimetry in MST.
Fluctuations are expected to play an important role in anomalous particle, momentum, and energy transport for magnetic confinement devices. Magnetic and density fluctuations are simultaneously measured using a high-speed laser-based Faraday rotation-interferometry system with a bandwidth of 500 kHz and 8 cm chord spacing. Density fluctuation and magnetic fluctuation profiles are obtained by using a newly developed fitting procedure.


Beyond 3DMM: Learning to Capture High-Fidelity 3D Face Shape.
3D Morphable Model (3DMM) fitting has widely benefited face analysis due to its strong 3D priori. However, previous reconstructed 3D faces suffer from degraded visual verisimilitude due to the loss of fine-grained geometry, which is attributed to insufficient ground-truth 3D shapes, unreliable training strategies and limited representation power of 3DMM. To alleviate this issue, this paper proposes a complete solution to capture the personalized shape so that the reconstructed shape looks identical to the corresponding person. Specifically, given a 2D image as the input, we virtually render the image in several calibrated views to normalize pose variations while preserving the original image geometry. A many-to-one hourglass network serves as the encode-decoder to fuse multiview features and generate vertex displacements as the fine-grained geometry. Besides, the neural network is trained by directly optimizing the visual effect, where two 3D shapes are compared by measuring the similarity between the multiview images rendered from the shapes. Finally, we propose to generate the ground-truth 3D shapes by registering RGB-D images followed by pose and shape augmentation, providing sufficient data for network training. Experiments on several challenging protocols demonstrate the superior reconstruction accuracy of our proposal on the face shape.


Immunohistochemical comparison of new monoclonal antibody 1C5 and carcinoembryonic antigen in the differential diagnosis of adenocarcinoma of the uterine cervix.
The reactivities of new monoclonal antibody 1C5 and anti-carcinoembryonic antigen (CEA) were determined immunohistochemically in 4 adenocarcinomas in situ, 20 invasive adenocarcinomas of various types, and 6 adenosquamous carcinomas of the uterine cervix, as well as in 10 endometrial adenocarcinomas and 10 normal cervices. Among the invasive adenocarcinomas, 90% were positively stained by 1C5 and 55% stained for CEA. Three of four in-situ adenocarcinomas were positively stained by 1C5 and two of four were positively stained by anti-CEA. All adenosquamous carcinomas were stained by 1C5 and four of six stained for CEA. Invasive adenocarcinomas always stained more intensely with 1C5 than did noninvasive lesions in the same specimen. Poorly differentiated adenocarcinomas were stained as strongly with 1C5 as were well-differentiated tumors, but CEA was less effective in identifying poorly differentiated lesions. 1C5 was also more useful than CEA was in distinguishing glandular from squamous neoplastic differentiation, and also appears to be useful in distinguishing endocervical from endometrial differentiation.


Potential-Energy Surfaces for Ring-Puckering Motions of Flexible Cyclic Molecules through Cremer-Pople Coordinates: Computation, Analysis, and Fitting.
Ring-puckering motion in 12 flexible cyclic molecules is investigated by calculation and analysis of two-dimensional potential-energy surfaces (PESs) using the so-called ring-puckering coordinates proposed by Cremer and Pople. The PESs are calculated by means of density-functional theory using a B2PLYP-D3BJ exchange-correlation functional with a maug-cc-pVTZ basis set, and results are compared to the available experimental and theoretical data. Special care is devoted to the aspect of symmetry in such two-dimensional PESs, which are here reported for the first time also for molecules whose planar form has symmetry lower than D5 h or C2 v. The issue of PES fitting and that of solving the nuclear dynamics using ring-puckering coordinates are also addressed. Analytical formulations of the computed PESs using suitable functional forms with a limited set of parameters are provided.


Dyslipidemia and diabetes: a personal view.
Cardiovascular disease, the main cause of morbidity and mortality in patients with diabetes, justifies an aggressive approach to the reduction of modifiable risk factors. Lipid values are generally normal in patients with insulin-dependent diabetes mellitus, but hypertriglyceridemia and low levels of high-density lipoprotein (HDL) cholesterol are frequently associated with non-insulin-dependent diabetes mellitus (NIDDM). Recommendations for screening and treatment of patients without diabetes do not apply to those with NIDDM. Screening should be done annually and should include fasting total cholesterol, triglycerides, and HDL cholesterol. Therapeutic recommendations based solely on the low-density lipoprotein cholesterol level are inappropriate. Hypertriglyceridemia cannot be ignored in patients with NIDDM. Therapy should first be directed toward improved control of the diabetes through diet, exercise, and insulin or sulfonylureas. Therapeutic goals are selected on the basis of individual risk assessment and are strongly influenced by the presence of preexisting vascular disease. When the goals are not achieved through improved control of diabetes, lipid-lowering drug therapy, based on the specific profile of the lipid abnormalities, should be initiated.


Biological effects of marine diesel oil exposure in red king crab (Paralithodes camtschaticus) assessed through a water and foodborne exposure experiment.
Shipping activities are expected to increase in the Arctic Seas. Today, the majority of vessels are using marine diesel oil (MDO) as propulsion fuel. However, there is a general lack of knowledge of how cold-water marine species respond to acute exposures to MDO. Arctic red king crabs (Paralithodes camtschaticus) were exposed to mechanically dispersed MDO in a flow-through exposure system for one week followed by three weeks of recovery. Observations of increased movements in exposed crabs were interpreted as avoidance behaviour. Further, glutathione peroxidase activity increased in high exposed crab, the catalase activity showed an insignificant increase with exposure, while no differences between groups were observed for lipid peroxidation and acetylcholinesterase activity. After three weeks of recovery in clean seawater, polycyclic aromatic hydrocarbons concentrations in the crabs were significantly reduced, with no specific biomarker responses in exposed groups compared to the control. The results suggest that effects from instantaneous MDO spill only will have short-term effects on the red king crab.


Recurrent atypical fibroxanthoma with satellite metastasis.
Atypical fibroxanthoma (AFX) is a cutaneous neoplasm of uncertain etiology that develops on sun-exposed regions of elderly males. It is widely considered to act indolently, despite its highly malignant cytologic features. Reports of metastatic AFX are very rare, and recurrence is uncommon. We report a case of recurrent AFX exhibiting a pattern of satellite metastasis followed by evidence of regional lymph node metastasis. A 76-year-old male with prior occupational and therapeutic radiation exposure and numerous squamous cell carcinomas had AFX of the left vertex scalp limited to the dermis completely removed by micrographic surgery. Twenty months later, multiple lesions appeared at the site of previous surgery. Imaging revealed no metastases or calvarial involvement. Wide local excision showed multiple well-defined nodules involving dermis and subcutis. The primary and recurrent neoplasms were similar and composed of pleomorphic epithelioid and spindled cells with marked nuclear atypia, hyperchromasia and mitotic activity. Immunohistochemistry was positive for CD10, procollagen1 and vimentin and negative for cytokeratins AE1/AE3, cytokeratins 5/6, 34βE12, MNF116, p63 CD31, Mart1, smooth muscle actin, desmin, S100 and CD34. Forty-eight months after removal of the primary, left intraparotid and posterior triangle lymph nodes are suspected to be involved by metastasis using clinical and positron emission tomography/ computed tomography examinations.


Cell culture adapted sheeppox virus as a challenge virus for potency testing of sheeppox vaccine.
Sheeppox virus from an outbreak of sheeppox that occurred in Srinagar (Jammu and Kashmir, India) in 2000 was isolated by inoculation of susceptible sheep and further re-isolated in cell culture. The field virus, adapted to grow in lamb testes culture, was evaluated for its potential use as challenge virus in potency testing of sheeppox vaccine currently in use. The virus (passage 6) produced severe disease in susceptible sheep when inoculated subcutaneously with a dose of 106.2 TCID50. The virus identity was confirmed by PCR, sequencing of P32 gene and species-specific signature residues identified in deduced aa sequence of the gene. The virus was successfully evaluated for its virulence using two batches of sheep pox vaccines. Use of this field virus enables consistent potency experiments of sheeppox vaccines avoiding use of animals for its propagation and titration.


[Not Available].
In the work submitted, the author makes a brief historical review of Bulgarian ethnographic literature, related, among other things, also to popular medicine investigations. Reference is made to authors as Dr. Yuri Ivanovich Venelin (1825), G.S. Rakovsky (1859), and after the liberation of Bulgaria: Tzani Ginchev Shkeparnev, one of the outstanding protagonists for collecting facts and materials in the field of popular medicine in this country, M. Georgiev, Hr. Popstoilov, K. Irechek, Iv. D. Shishmanov and others. A description is made of the traditional methods of treatment with herbs, charms, healers and the like. Due attention is given also to the popular conceptions and explanation of the contributing factors of diseases, looking for the rationale in them and giving special consideration to the superstitious traces, inherited from the ancient Thracians. It is stressed that the items published heretofore in the "Comopilation of national folklore and literature", covering the field of popular medicine, constitute a great, unique in its significance, national wealth which is seldom found in other countries and which might be utilized by modern medicine as well as for drawing important ethnogenetic inferences.


Observation of Intramural Fibroid Expulsion on MRI after Uterine Artery Embolization.
Uterine artery embolization (UAE) is a type of noninvasive treatment for symptomatic uterine fibroids. One of the complications of UAE is fibroid expulsion. Here, we report a case of a 45-year-old woman who underwent UAE for an intramural fibroid, which resulted in fibroid expulsion. To the best of our knowledge, there are only few reports of expulsion of intramural fibroids. The process of fibroid protrusion from the myometrium into the uterine cavity was depicted on magnetic resonance imaging (MRI) in this case. We discuss the risk factors and mechanisms of fibroid expulsion after UAE.


Single-stage denitrifying phosphorus removal biofilter utilizing intracellular carbon source for advanced nutrient removal and phosphorus recovery.
Advanced nutrient removal of municipal wastewater has insufficient carbon source, and resource recovery is neglected. In this study, a single-stage biofilter based on denitrifying phosphorus removal (DPR) was proposed for advanced nutrient removal and phosphorus recovery, which was operated under alternating anoxic/anaerobic mode with no extracellular carbon source in anoxic period. The results showed that the biofilter achieved efficient and stable performance with low carbon consumption (C/N ≈ 3.7). The average removal efficiency of NO3--N, TN and PO43--P were 74.81%, 71.08% and 91.15%, respectively. DPR primarily occurred in the middle of the filtration bed and nutrient removal was driven by intracellular polymers, which was the main carbon source. High-throughput sequencing indicated that Dechloromonas was enriched and contributed to DPR while Zoogloea was responsible for endogenous denitrification. Denitrifying polyphosphate accumulating organisms and endogenous denitrifiers synergistically enhanced the nutrient removal capacity. The study further provides research perspectives for improving nutrient removal.


Public health-specific National Incident Management System trainings: building a system for preparedness.
Local health departments (LHDs) are at the hub of the public health emergency preparedness system. Since the 2003 issuance of Homeland Security Presidential Directive-5, LHDs have faced challenges to comply with a new set of all-hazards, 24/7 organizational response expectations, as well as the National Incident Management System (NIMS). To help local public health practitioners address these challenges, the Centers for Disease Control and Prevention-funded Johns Hopkins Center for Public Health Preparedness (JH-CPHP) created and implemented a face-to-face, public health-specific NIMS training series for LHDs. This article presents the development, evolution, and delivery of the JH-CPHP NIMS training program. In this context, the article also describes a case example of practice-academic collaboration between the National Association of County and City Health Officials and JH-CPHP to develop public health-oriented NIMS course content.


Bile Acid Detection Techniques and Bile Acid-Related Diseases.
Bile acid is a derivative of cholinergic acid (steroidal parent nucleus) that plays an important role in digestion, absorption, and metabolism. In recent years, bile acids have been identified as signaling molecules that regulate self-metabolism, lipid metabolism, energy balance, and glucose metabolism. The detection of fine changes in bile acids caused by metabolism, disease, or individual differences has become a research hotspot. At present, there are many related techniques, such as enzyme analysis, immunoassays, and chromatography, that are used for bile acid detection. These methods have been applied in clinical practice and laboratory research to varying degrees. However, mainstream detection technology is constantly updated and replaced with the passage of time, proffering new detection technologies. Previously, gas chromatography (GS) and gas chromatography-mass spectrometry (GC-MS) were the most commonly used for bile acid detection. In recent years, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has developed rapidly and has gradually become the mainstream bile acid sample separation and detection technology. In this review, the basic principles, development and progress of technology, applicability, advantages, and disadvantages of various detection techniques are discussed and the changes in bile acids caused by related diseases are summarized.


INHIBITION OF GROWTH OF CHICK EMBRYO BY INHIBITION OF DEOXYCYTIDYLATE DEAMINASE.
Deoxyguanylate when added to chick embryos grown in explant inhibited growth and development. Deoxycytidylate deaminase activity was inhibited both in the explants and in vitro; since the effect was quite specific, it is suggested that this may represent another control mechanism for deoxynucleotide synthesis.


Immune responses to an oral typhoid vaccine strain that is modified to constitutively express Vi capsular polysaccharide.
Protection against typhoid fever might be best achieved by a vaccine that stimulates IgG antibody to Vi capsular polysaccharide (Vi) in serum, IgG antibody to O antigen in serum, and cell-mediated immune responses. Live typhoid vaccines have not elicited anti-Vi antibody, presumably because Vi expression is highly regulated. CVD 909 is an oral attenuated typhoid vaccine candidate that is engineered to constitutively express Vi. In the present study, CVD 909, at doses of 10(6-9) cfu, was orally administered to 32 healthy adults, and immune responses were measured. Although many of the volunteers generated antibody-secreting cell responses to Vi, only 2 of the 32 volunteers generated anti-Vi IgG antibody in serum.


Electrophoretic mobility profiles of mouse leukemias. II. Electrophoresis of thymic lymphoma, myeloid leukemia and reticulum sarcoma cells.
Electrophoretic mobility of cells from 21 primary mouse leukemias was investigated and compared with that of various normal mouse reference cells. Six thymic lymphomas, nine reticulum cell sarcomas, five myeloid leukemias and one stem-cell leukemia were examined. The mean AEM of cells from the group of primary thymic lymphomas (1.13 microns s-1 V-1 cm) was similar to that of reticulum cell sarcomas (1.15 microns s-1 V-1 cm) and significantly lower than that of the myeloid leukemias (1.20 microns s-1 V-1 cm). Since the examined cell suspensions were prepared from leukemic lymph nodes, the analysis was performed to investigate the possible admixture of normal LNC in the cell populations. Electrophoretograms of normal and leukemic lymph nodes were compared and the AEM of cells from leukemic lymph nodes was considered separately for two cell populations, one corresponding in size to normal LNC (6-9 microns in diameter) and the other to leukemic blast cells (10-16 microns in diameter). In the 6-9 microns cell subpopulations from leukemic lymph nodes, electrophoretically slow cells corresponding to B LNC were almost totally depleted (1%); also electrophoretically fast cells with the mean AEM of T LNC were fewer (45-57%) than in normal LNC populations. The leukemic cells 10-16 microns in diameter displayed mean AEM of 1.09 (thymic lymphomas), 1.12 (reticulum cell sarcomas) and 1.21 (myeloid leukemia) micron s-1 V-1 cm. The mean AEM of blast cells from thymic lymphomas and reticulum cell sarcomas was not significantly different; it was similar to that of blast cells prepared from normal mouse thymus (1.09 microns s-1 V-1 cm) on a density gradient. In contrast, the 10-16 microns cell populations from lymph nodes of mice with myeloid leukemias were significantly faster than blast cells from thymic lymphomas and reticulum cell sarcomas.


IVF or ICSI for fertility preservation?
In IVF, eggs and sperm are added together for fertilisation to occur whereas ICSI involves injecting a single sperm into each egg. ICSI is very effective where sperm count or swimming is poor (male infertility) but is slightly riskier than IVF in terms of health problems in children, although these risks are small. However, the risk of no eggs fertilising is higher for IVF compared to ICSI and couples undertaking fertility preservation, for example, before cancer treatment, usually only have time for one attempt. Using fertility preservation treatment cycle data reported to Human Fertilisation and Embryology Authority (HFEA), this study shows that ICSI results in higher number of fertilised eggs and embryos for storage or treatment compared to IVF. However, 19% of eggs are not used in ICSI treatment, so IVF appears to be better overall. Clinics should choose IVF or ICSI for fertility preservation depending on sperm characteristics rather than using ICSI for all.


The iron-responsive regulator fur is transcriptionally autoregulated and not essential in Neisseria meningitidis.
Fur is a well-known iron-responsive repressor of gene transcription, which is used by many bacteria to respond to the low-iron environment that pathogens encounter during infection. The fur gene in Neisseria meningitidis has been described as an essential gene that may regulate a broad array of genes. We succeeded in obtaining an N. meningitidis mutant with the fur gene knocked out and used it to undertake studies of fur-mediated iron regulation. We show that expression of both Fur and the transferrin binding protein Tbp2 is iron regulated and demonstrate that this regulation is Fur mediated for the Tbp2 protein. Footprinting analysis revealed that Fur binds to two distinct sites upstream of its coding region with different affinities and that these binding sites overlap two promoters that differentially control transcription of the fur gene in response to iron. The presence of two independently regulated fur promoters may allow meningococcus to fine-tune expression of this regulator controlling iron homeostasis, possibly during infection.


Bleeding, obstruction, and perforation in a series of patients with aggressive gastric lymphoma treated with primary chemotherapy.
The management of patients with gastric lymphoma has evolved, with a shift toward nonsurgical treatment. The rates of surgical complications in patients receiving chemotherapy have been insufficiently studied. The objective of this study was to assess the frequency of bleeding, perforation, and gastric outlet obstruction in patients who received chemotherapy as primary treatment for gastric diffuse large B cell lymphoma (DLBCL). We reviewed files of all patients with gastric DLBCL who were diagnosed and treated primarily with chemotherapy in our hospital between 1990 and 2005. Eighteen (25%) of 73 patients experienced surgical complications, of whom 6 (8%) underwent surgery. Eight patients (11%), six with active lymphoma, experienced gastric bleeding; one required gastrectomy. Eight patients (11%) developed gastric outlet obstruction, of whom three were treated conservatively, three required surgery, one stopped treatment, and one received further chemotherapy. Six of the eight patients had no evidence of active lymphoma at the time of obstruction. Two additional patients underwent gastrectomy due to resistant or relapsed disease. Gastric perforation was not observed. Median survival was 90 months for the entire series, 94 months for patients with gastric outlet obstruction, and 11.5 months for patients with gastric bleeding. Given the rate of surgical complications, especially gastric bleeding and gastric outlet obstruction, there is still an important role for the surgical consultant in the treatment of patients with gastric DLBCL receiving chemotherapy. Gastric perforation, although frequently cited as a complication, is in fact rarely observed.


Kidney organogenesis and regeneration: a new era in the treatment of chronic renal failure?
The recent development of a strategy to establish human inducible pluripotent stem (iPS) cells has created a second surge in the field of regenerative research, which had been slowed by restrictions on the use of pluripotent embryonic stem cells. Research on regenerative nephrology offers hope for patients on dialysis. However, due to its anatomic complexity, the kidney is the most difficult organ for the application of regenerative medicine. Very recently, the establishment of a functional whole kidney has been attempted using various stem cells, which may lead to clinical applications. We review recent progress in the field of regenerative nephrology, focusing on the de novo establishment of a whole kidney.


The vasoactive intestinal peptide (VIP) alpha-Helix up to C terminus interacts with the N-terminal ectodomain of the human VIP/Pituitary adenylate cyclase-activating peptide 1 receptor: photoaffinity, molecular modeling, and dynamics.
The neuropeptide vasoactive intestinal peptide (VIP) strongly impacts on human pathophysiology and does so through interaction with class II G protein-coupled receptors. We characterized the C terminus-binding site of VIP in the N-terminal ectodomain (N-ted) of the human VPAC1 receptor: 1) The probe [(125)I-Bpa(28)]VIP in which the C-terminal residue (Asn(28)) is substituted by a photoreactive p-benzoyl-l-Phe (Bpa) was used to photolabel the receptor. After receptor cleavage and Edman sequencing, it was shown that Asn(28) of VIP is in contact with Lys(127) in the receptor N-ted. Taking into account previous data, it follows that the C-terminal and central parts of VIP from Asn(28) to Phe(6) lie in the N-ted. 2) A three-dimensional model of the N-ted was constructed, the fold being identified as a Sushi domain with two antiparallel beta-sheets and three disulfide bonds. The nuclear magnetic resonance structure of VIP was then docked into this model by taking into account the constraint provided by photoaffinity experiments with [(125)I-Bpa(28)]VIP. It appeared that VIP runs parallel to the beta3-beta4 antiparallel sheets. 3) We performed molecular dynamic simulations over 14 nsec of the complex between VIP and receptor N-ted and the free N-ted. The structural model of the free N-ted is stable, and VIP tends to further stabilize the N-ted structure more especially in the loops connecting the beta-sheets. These structural studies provide a detailed molecular understanding of the VIP-receptor interaction.


Effect of antiviral agents on replication of herpes simplex virus type 1 in brain cultures.
An in vitro tissue culture system consisting of reaggregated embryonic brain cells was used to evaluate the inhibition of herpes simplex type 1 (HSV-1) by several antiviral compounds. The efficacy of acyclovir, vidarabine, bromovinyldeoxyuridine, and 9-(1,3-dihydroxy-2-propoxymethyl) guanine in HSV-1-infected Vero cell monolayer cultures was compared with that seen with brain cell aggregates. At a mean 50% inhibitory dose with Vero cells, acyclovir showed a 99% reduction of virus titer in brain cell aggregates. Vidarabine and 9-(1,3-dihydroxy-2-propoxymethyl) guanine gave a dose-dependent reduction in virus titer with Vero cells; however, in aggregate cultures treated with the same drugs a dose-dependent decrease at 24 h was followed by an increase to a point of no inhibition at 72 h postinfection. Pretreatment of brain cell aggregates with a hybrid human leukocyte interferon (Le IF-AD) reduced virus titers at 48 h postinfection but did not maintain this reduction at 72 h. In contrast, infected Vero cell monolayer cultures demonstrated a dose-dependent reduction in virus titers with Le IF-AD. Postinfection treatment with Le IF-AD did not reduce plaque formation in Vero cells but was effective in reducing virus titer in HSV-1-infected brain cell aggregates at 48 h postinfection. Antiviral concentrations of up to 200 micrograms or 200,000 IU/ml for interferon did not appear morphologically toxic to brain cells. Antiviral therapy of HSV-1-infected brain cell aggregates may more closely mimic in vivo responses than monolayer cultures.


Impact of Ancestral Differences and Reassessment of the Classification of Previously Reported Pathogenic Variants in Patients With Brugada Syndrome in the Genomic Era: A SADS-TW BrS Registry.
Brugada syndrome (BrS) is a heritable disease that results in sudden cardiac death. In the exome/genomic era, certain reported pathogenic variants in some genetic diseases have been reclassified as benign owing to their high frequency in some ancestries. In the present study, we comprehensively reassessed all previously reported pathogenic variants of BrS. We collected all pathogenic variants of BrS reported in the Human Gene Mutation Database and ClinVar throughout April 2017. We compared the minor allele frequency (MAF) of each variant among different ancestries by searching public whole-genome and exome databases. After considering the maximum credible allele frequency, variants with a MAF ≥ 0.001 were considered to be of questionable pathogenicity. We also investigated the percentage of SCN5A variants with a MAF ≥ 0.001 in 124 BrS patients from the Han Chinese population. We collected a total of 440 BrS variants, of which 18 had a MAF ≥ 0.001. There was a greater percentage of non-SCN5A variants with a MAF ≥ 0.001 than of SCN5A variants (21.8 versus 1.6%, p < 0.0001). There were fewer frameshift and nonsense mutations than missense mutations (0.9 versus 5.6%, p = 0.032). Of the 18 variants, 14 (77.8%) were present only in the reference Asian population. In our cohort, we identified two SCN5A variants (p.A226V and p.V1340I) with MAFs ≥ 0.001 (0.45%). In conclusion, ancestral differences are important when considering the pathogenicity of BrS variants, especially in the case of missense variants and non-SCN5A variants, which may be pathogenic in some ancestries but only disease-predisposing in others.


Sphingopyxis panaciterrae sp. nov., isolated from soil from ginseng field.
A Gram-negative, strictly aerobic, motile bacterial strain, designated Gsoil 124T, was isolated from a soil sample taken from a ginseng field in Pocheon Province (South Korea). The isolate contained Q-10 as the predominant lipoquinone, plus C18:1 7c and summed feature 4 (C16:1 6c and/or iso- C15:0 2-OH) as the major fatty acids. The G+C content of the genomic DNA was 68.1 mol%, and the major polar lipids consisted of sphingoglycolipid, phosphatidylglycerol, phosphatidylcholine, and phosphatidylethanolamine. A comparative 16S rRNA gene sequence analysis showed that strain Gsoil 124T was most closely related to Sphingopyxis chilensis (98.7%), Sphingopyxis alaskensis (98.2%), Sphingopyxis witflariensis (98.2%), Sphingopyxis taejonensis (98.0%), and Sphingopyxis macrogoltabida (97.6%). However, the DNA-DNA relatedness between strain Gsoil 124T and its phylogenetically closest neighbors was less than 22%. Thus, on the basis of its phenotypic properties and phylogenetic distinctiveness, strain Gsoil 124T should be classified as representing a novel species in the genus Sphingopyxis, for which the name Sphingopyxis panaciterrae sp. nov. is proposed. The type strain is Gsoil 124T (=KCTC 12580T=LMG 24003T).


Molecular Guided Treatments in Gynecologic Oncology: Analysis of a Real-World Precision Cancer Medicine Platform.
Advanced gynecologic cancers have a poor prognosis and constitute a major challenge for adequate treatment strategies. By analyzing and targeting molecular alterations, molecular guided treatments may be a viable option for the treatment of advanced gynecologic cancers. In this single-center, real-world retrospective analysis of our platform for precision cancer medicine (PCM), we describe the molecular profiling of 72 patients diagnosed with different types of advanced gynecologic malignancies. Tumor samples of the patients were examined by next-generation sequencing panel and immunohistochemistry (IHC). In total, we identified 209 genetic aberrations in 72 patients. The ten most frequent alterations were TP53 (n = 42, 20%), KRAS (n = 14, 6.6%), PIK3CA (n = 11, 5.2%), PIK3R1 (n = 9, 4.3%), ATR (n = 8, 3.8%), PTEN (n = 8, 3.8%), BRCA1 (n = 6, 2.8%), NF1 (n = 4, 1.9%), NOTCH1 (n = 4, 1.9%), and POLE (n = 4, 1.9%), which account for more than half of all molecular alterations (52.6%). In 21 (29.1%) patients only one mutation could be detected, and 44 (61.1%) patients had more than one mutation. No molecular alterations were detected in seven (9.7%) patients. IHC detected expression of phosphorylated mammalian target of rapamycin and epidermal growth factor receptor in 58 (80.6%) and 53 (73.6%) patients, respectively. In over two thirds (n = 49, 68.1%), a targeted therapy was suggested, based on the identified genetic aberrations. The most frequently recommended specific treatment was the combination of everolimus with exemestane (n = 18, 25 %). Based on our observations, it seems that PCM might be a feasible approach for advanced gynecologic cancers with limited treatment options. Nowadays molecular profiling of advanced gynecologic malignancies is feasible in the clinical routine. A molecular portrait should be done for every patient with an advanced therapy-refractory gynecologic malignancy to offer molecular-based treatment concepts.


Nuclear and Cellular Abnormalities of Erythrocytes in Response to Thermal Stress in Common Carp Cyprinus carpio.
As a consequence of global warming, increase of water temperature is likely to alter physiological functions of fish. Hence, we examined the effects of high temperature on blood glucose, hematological parameters [hemoglobin (Hb), red blood cell (RBC), and white blood cell (WBC)], and nuclear and cellular structure of blood cells of common carp (Cyprinus carpio) after exposure to three temperature regimes (27, 31, and 35°C) for 14 days. Fish were sacrificed on 3, 7, and 14 days of exposure. The blood glucose level increased significantly in the fish exposed to 35°C compared to 27 and 31°C. The Hb and RBC contents decreased but WBC increased significantly in the blood of fish exposed to 35°C compared to 27 and 31°C at 7 and 14 days of exposure. Consequently, the frequencies of erythroblasts (Ebs), erythrocytic nuclear abnormalities (ENA), and erythrocytic cellular abnormalities (ECA) were found to be increased in the blood of fish exposed to 35°C compared to 27 and 31°C. There was a significant increase in neutrophils and decrease in lymphocytes in the highest temperature (35°C). With increasing temperature, dissolved oxygen (DO) decreased but free CO2 increased significantly during the study period. The present study demonstrated that common carp are better adapted to 27 and 31°C environmental temperatures, while the higher temperature 35°C is likely stressful to this fish species.


Selective activation of parvalbumin- or somatostatin-expressing interneurons triggers epileptic seizurelike activity in mouse medial entorhinal cortex.
GABAergic interneurons are thought to play a critical role in eliciting interictal spikes (IICs) and triggering ictal discharges in temporal lobe epilepsy, yet the contribution of different interneuronal subtypes to seizure initiation is still largely unknown. Here we took advantage of optogenetic techniques combined with patch-clamp and field recordings to selectively stimulate parvalbumin (PV)- or somatostatin (SOM)-positive interneurons expressing channelrhodopsin-2 (CHR-2) in layers II-III of adult mouse medial entorhinal cortical slices during extracellular perfusion with the proconvulsive compound 4-aminopyridine (4-AP, 100-200 μM). In control conditions, blue laser photostimulation selectively activated action potential firing in either PV or SOM interneurons and, in both cases, caused a robust GABAA-receptor-mediated inhibition in pyramidal cells (PCs). During perfusion with 4-AP, brief photostimuli (300 ms) activating either PV or SOM interneurons induced patterns of epileptiform activity that closely replicated spontaneously occurring IICs and tonic-clonic ictal discharges. Laser-induced synchronous firing in both interneuronal types elicited large compound GABAergic inhibitory postsynaptic currents (IPSCs) correlating with IICs and preictal spikes. In addition, spontaneous and laser-induced epileptic events were similarly initiated in concurrence with a large increase in extracellular potassium concentration. Finally, interneuron activation was unable to stop or significantly shorten the progression of seizurelike episodes. These results suggest that entorhinal PV and SOM interneurons are nearly equally effective in triggering interictal and ictal discharges that closely resemble human temporal lobe epileptic activity.


Suicides among farmers in three southeastern states, 1990-1998.
Several studies have documented higher rates of suicide among farmers in comparison to other occupational groups, both in the U.S. and internationally. The purpose of this study is to describe the epidemiology of farmer suicides in three southeastern states (Kentucky, North Carolina, and South Carolina) during the nine-year period 1990-1998. Electronic death certificate data were obtained from the National Center for Health Statistics. Over the nine-year period, there were 590 deaths related to suicide (E-codes: 950-959) among farmers (occupation codes: 473, 474, 475, 477, and 479) in the states of Kentucky, North Carolina, and South Carolina. The results of this study confirm the increased rate of suicide mortality among white male farmers in comparison to the total white male population in these three southern states. The increased rate of suicide was significantly elevated among farmers age 25-34 years (RR: 2.07; 95% CI: 1.61-2.67) and among those age 75-84 (RR: 2.04; 95% CI: 1.70-2.45) and age 85 years and older (RR: 2.67; 95% CI: 2.02-3.54) in comparison to the total white male population.The use of a firearm was the primary mechanism of death for the majority (86%) of the cases. Farmer suicide mortality rates in the southeastern U.S. are higher than in Midwestern states. The elevated rate of white male farmer suicides in North Carolina over this time period (35% higher age-adjusted suicide rate in comparison to South Carolina) suggests a need for further investigation to assess the individual, social, and economic factors that may explain this elevated rate. Interventions for the prevention of suicide need to be directed to older male farmers who consistently have higher suicide rates than similar males in other occupations.


The Role of Personality in Becoming Aware of Age-Related Changes.
Awareness of age-related change (AARC) refers to an individual's conscious knowledge about the gains and losses resulting from growing older. Personality traits reflect dispositional patterns of behavior, perception, and evaluation and should therefore influence the experience of AARC. The 4.5-year longitudinal study examines this association between personality traits and AARC in a sample of 423 individuals aged 40 to 98 years (M = 62.9 years) using latent change analyses. After controlling for sex, health, and education, a different pattern of associations for cross-sectional vs. longitudinal relations. Cross-sectionally, neuroticism was positively related to AARC losses, whereas openness, conscientiousness, and neuroticism were positively related to AARC gains. Longitudinally, the impact of personality traits on change in AARC was rather limited with only higher conscientiousness acting as a predictor of decreases in AARC losses over time. Overall, the findings add to the existing literature on associations between personality traits and subjective aging. Specifically, the results indicate that personality traits are differentially related to awareness of age-related gains in comparison to awareness of age-related losses.


Morphometric analysis of the infraorbital foramen and its localization relative to surgical landmarks.
The infraorbital foramen (IOF) is an important anatomic landmark for maxillofacial surgery; therefore, its location should be well documented. In morphometric analyses of the IOF, various methods have been applied and differences have been found among the results of the measurements. The aim of this study was to facilitate localization of the IOF during clinical practice. In the current study, in order to perform anatomic and morphometric analyses of the IOF, 112 skulls were used. The shortest distance from each IOF to certain determined points was identified and measured by digital calipers. The longest and the shortest diameters of the IOF were measured as 4.21±0.91 mm and 3.11±0.62 mm, respectively. The shortest distances between the IOF and the landmarks were measured as follows: the maxillary mid-line (ML) as 28.47±2.49 mm; the supraorbital foramen/supraorbital notch (SOF/SON) as 43.43±3.39 mm; the lower end of the nasomaxillary suture (LENS) as 26.47±3.05 mm; the lower end of the alveolar juga of the canines (LAJC) as 31.62±3.09 mm; the infra-orbital margin (IOM) as 6.98±1.72 mm; and the opposite IOF as 56.85±3.89 mm. Among the landmarks, the most useful ones in clinical practice might be the distances between the IOF and the IOM, IOF and LAJC, and even IOF and ML. SOF/SON and LENS provide more accurate localization when they are used together with the other parameters. Moreover, their importance increases when other parameters are not available for use (because of fractures or damage).


A novel point mutation in the insulin gene giving rise to hyperproinsulinemia.
A 58-yr-old obese white Caucasian male type 2 diabetic, entered into the UK Prospective Diabetes Study, was found to have raised fasting total proinsulin levels 708 pmol/L(-1) (normal range, 3-16 pmol/L(-1)) and normal specific plasma insulin level 29 pmol/L(-1) (normal range, 21-75 pmol/L(-1)). Immunoreactive plasma insulin, measured by RIA, was 503 pmol/L(-1). DNA was extracted, the insulin gene amplified by the PCR, and by direct sequencing, a novel point mutation, G1552C, was identified, which resulted in the substitution of proline (CCT) for arginine (CGT) at position 65. This prevented cleavage of the C-peptide A-chain dibasic cleavage site (lys-arg) by the processing protease in the pancreatic beta-cells. The plasma proinsulin and insulin levels were in accord with expression of both the wild-type and the mutant alleles. The G1552C mutation was not linked with diabetes, because it was present in a 37-yr-old nondiabetic daughter and not in a 35-yr-old daughter who had had gestational diabetes.


Basics of Compounding with Dilutions and Concentrates.
Pharmacists use various sources for obtaining the active pharmaceutical ingredient for compounding medications. In many cases, it is the pure drug (United States Pharmacopeia, National Formulary, or similar grade); in some cases, it can be a commercial dosage form; and, in some cases, it may be a dilution or concentrate. If the drug is not present at full strength, then adjustments may be necessary to obtain the required quantity of drug. Also, in many cases, it is necessary to use a dilution or a concentrate of a drug due to safety and quality reasons. Presented within this article are new sources of active pharmaceutical ingredients that are now available to aid pharmacists in meeting future United States Pharmacopeia <800> standards. It is critical that the pharmacist be aware of the strength of the drug and any other excipients that may be available.


[The Relevance of MicroRNAs in Glioblastoma Stem Cells].
Glioblastoma multiforme is the most common intracranial malignity of astrocyte origin in adults. Despite complex therapy consisting of maximal surgical resection, adjuvant concomitant chemoradiotherapy with temozolomide followed by temozolomide in monotherapy, the median of survival ranges between 12 and 15 months from dia-gnosis. This infaust prognosis is very often caused by both impossibility of achieving of sufficient radical surgical resection and tumor resistance to adjuvant therapy, which relates to the presence of glioblastoma stem cells. Similarly to normal stem cells, glioblastoma stem cells are capable of self -renewal, differentiation, and unlimited slow proliferation. Their resistance to conventional therapy is also due to higher expressions of DNA repair enzymes, antiapoptotic factors and multidrug transporters. Therefore, targeting these unique properties could be a novel promising therapeutic approach leading to more effective therapy and better prognosis of glioblastoma multiforme patients. One of the approaches how to successfully regulate above -mentioned properties is targeted regulation of microRNAs (miRNAs). These small noncoding RNA molecules posttranscriptionally regulate expression of more than 2/ 3 of all human genes that are also involved in stem cell associated signaling pathways. Moreover, deregulated expression of some miRNAs has been observed in many cancers, including glioblastoma multiforme.


Historical perspective, development and applications of next-generation sequencing in plant virology.
Next-generation high throughput sequencing technologies became available at the onset of the 21st century. They provide a highly efficient, rapid, and low cost DNA sequencing platform beyond the reach of the standard and traditional DNA sequencing technologies developed in the late 1970s. They are continually improved to become faster, more efficient and cheaper. They have been used in many fields of biology since 2004. In 2009, next-generation sequencing (NGS) technologies began to be applied to several areas of plant virology including virus/viroid genome sequencing, discovery and detection, ecology and epidemiology, replication and transcription. Identification and characterization of known and unknown viruses and/or viroids in infected plants are currently among the most successful applications of these technologies. It is expected that NGS will play very significant roles in many research and non-research areas of plant virology.


Alpha-1-antitrypsin deficiency (Siiyama) as indication for lung transplantation: proper timing for surgical intervention.
The authors report a new familial case of alpha-1- antitrypsin (AAT) deficiency with severe pulmonary emphysema and hemoptysis. A severely reduced serum AAT level of the proband, a 56-year-old farmer's wife and her sister were observed. Mutation analysis of the AAT gene was performed using allele-specific polymerase chain reaction (PCR) analysis followed by direct sequencing. The proband and her younger sister proved to be homozygous for PISiiyama. Although home oxygen therapy was induced in addition to previous medications including bronchodilators and cardiovascular conditioning, the proband's rate of decline of forced expiratory volume at one second (FEV1) was progressing. Lung transplantation was therefore advisable for the patient. Clinical analysis on Japanese cases reported in the literature shows that the rate of decline of FEV1 is one of the most convenient prognostic factors to find proper timing for surgical intervention. Lung transplantation is one of the best reliable current therapies to improve quality of life of severely impaired patients.


Chemotherapy in the management of infantile fibrosarcoma.
Infantile fibrosarcoma (IF) has traditionally been treated with surgery, which may have considerable morbidity. Chemotherapy has been suggested in order to reduce the need for extensive surgery. Nine children with histologically confirmed IF who received chemotherapy are described. Six children were treated with chemotherapy initially, two following conservative surgery, and one following recurrence after surgery. All received vincristine (V) and actinomycin D (A), and six received additional drugs including ifosfamide (I), cyclophosphamide (C), adriamycin (Ad), etoposide (E), and cisplatinum (CDDP). Objective responses were achieved in eight: three responded completely (CR), two responded partially (PR), which allowed conservative surgery, one had stable disease, one had an initial PR, but subsequently had tumour recurrence 1 month after cessation of treatment, necessitating further surgery and chemotherapy, and one had an initial PR but died following local and regional metastases. One child had no response to chemotherapy but is alive with stable residual disease. Thus, five of nine children achieved a CR--three with chemotherapy alone. With the inclusion of chemotherapy as part of their treatment, five children, for whom curative surgery may have resulted in amputation, remain alive with limbs intact. Chemotherapy including V and A should be given to infants with fibrosarcoma in whom curative surgery would be mutilating.


Molecular proximity of cystic fibrosis transmembrane conductance regulator and epithelial sodium channel assessed by fluorescence resonance energy transfer.
We present the evidence for a direct physical association of cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC), two major ion channels implicated in the pathophysiology of cystic fibrosis, a devastating inherited disease. We employed fluorescence resonance energy transfer, a distance-dependent imaging technique with capability to detect molecular complexes with near angstrom resolution, to estimate the proximity of CFTR and ENaC, an essential variable for possible physical interaction to occur. Fluorescence resonance energy transfer studies were complemented with a classic biochemical approach: coimmunoprecipitation. Our results place CFTR and ENaC within reach of each other, suggestive of a direct interaction between these two proteins.


Symmetry breaking in a few-body system with magnetocapillary interactions.
We have experimentally investigated the interactions between floating magnetic spheres which are submitted to a vertical magnetic field, ensuring a tunable repulsion, while capillary forces induce attraction. We emphasize the complex arrangements of floating bodies. The equilibrium distance between particles exhibits hysteresis when the applied magnetic field is modified. Irreversible processes are evidenced. Symmetry breaking is also found for three identical floating bodies when the strength of the magnetic repulsion is tuned. We propose a Dejarguin-Landau-Verwey-Overbeek (DLVO)-like potential, i.e., an interaction potential with a primary and a secondary minimum, capturing the main physical features of the magnetocapillary interaction, which is relevant for self-assembly.


Effects of difructose anhydride III (DFA III) administration on rat intestinal microbiota.
The effects of difructose anhydride III (di-D-fructofuranose-1,2':2,3'-dianhydride; DFA III) administration (3% DFA III for 4 weeks) on rat intestinal microbiota were examined using denaturing gradient gel electrophoresis (DGGE). According to DGGE profiles, the number of bacteria related to Bacteroides acidofaciens and uncultured bacteria within the Clostridium lituseburense group decreased, while that of bacteria related to Bacteroides vulgatus, Bacteroides uniformis and Ruminococcus productus increased in DFA III-fed rat cecum. In the cecal contents of DFA III-fed rats, a lowering of pH and an increase in short chain fatty acids (SCFAs), especially acetic acid, were observed. The DFA III-assimilating bacterium, Ruminococcus sp. M-1, was isolated from the cecal contents of DFA III-fed rats. The strain had 98% similarity with R. productus ATCC 27340T (L76595), and mainly produced acetic acid. These results confirmed that the bacteria harmful to host health were not increased by DFA III administration. Moreover, DFA III stimulated the growth of Ruminococcus sp. M-1 producing acetic acid, which may alter the intestinal microbiota towards a healthier composition. It is expected that DFA III would be a new candidate as a prebiotic.