Hearing thresholds in children with a congenital CMV infection: a prospective study.
Hearing thresholds in children with a congenital cytomegalovirus (cCMV) infection are not always stable. Children can develop late onset hearing loss, fluctuations, progression (worsening) and improvement of hearing loss. Knowledge about these characteristics is important to understand why long term follow up in these children is mandatory. We prospectively follow a cohort of 154 children with cCMV infection, 68 of which met the inclusion criteria of at least 3 hearing evaluations over a period of at least 18 months in the absence of other risk factors for hearing loss. In those 68 children we evaluated the occurrence of unstable hearing thresholds: late onset hearing loss, fluctuations, progression and improvement of hearing loss. Unstable hearing thresholds were observed in 29.4% of children with cCMV infection of which 19.2% were found in the group of children with ultimately normal hearing and in 62.5% of children with sensorineural hearing loss (SNHL) (p=0.0027). Fluctuations occurred in 16.2%. Late onset hearing loss occurred in 4.3% of children with a normal hearing at birth. In children with SNHL, progression or worsening of hearing thresholds occurred in 27.3% and improvement of thresholds in 40.9%. Important changes in thresholds only occurred in 13.2% of all children and predominantly in children who finally develop SNHL. Unstable hearing thresholds are frequently found in children with cCMV infection and occur not only in children who develop hearing losses but also in children who have a normal hearing at the last visit. Important changes in hearing thresholds of > 30 dB are more frequently seen in children who ultimately will develop SNHL.


Temperature-dependent physiological and biochemical responses of the marine medaka Oryzias melastigma with consideration of both low and high thermal extremes.
This study aimed to investigate temperature effect on physiological and biochemical responses of the marine medaka Oryzias melastigma larvae. The fish were subjected to a stepwise temperature change at a rate of 1 °C/h increasing or decreasing from 25 °C (the control) to six target temperatures (12, 13, 15, 20, 28 and 32 °C) respectively, followed by a 7-day thermal acclimation at each target temperature. The fish were fed ad libitum during the experiment. The results showed that cumulative mortalities were significantly increased at low temperatures (12 and 13 °C) and at the highest temperature (32 °C). For the survivors, their growth profile closely followed the left-skewed 'thermal performance curve'. Routine oxygen consumption rates of fish larvae were significantly elevated at 32 °C but suppressed at 13 and 15 °C (due to a high mortality, larvae from 12 °C were not examined). Levels of heat shock proteins and activities of malate dehydrogenase and lactate dehydrogenase were also measured in fish larvae exposed at 15, 25 and 32 °C. The activities of both enzymes were significantly increased at both 15 and 32 °C, where the fish larvae probably suffered from thermal discomfort and increased anaerobic components so as to compensate the mismatch of energy demand and supply at these thermal extremes. Coincidently, heat shock proteins were also up-regulated at both 15 and 32 °C, enabling cellular protection. Moreover, the critical thermal maxima and minima of fish larvae increased significantly with increasing acclimation temperature, implying that the fish could develop some degrees of thermal tolerance through temperature acclimation.


High e+/e- Ratio Dense Pair Creation with 10(21)W.cm(-2) Laser Irradiating Solid Targets.
We report results of new pair creation experiments using ~100 Joule pulses of the Texas Petawatt Laser to irradiate solid gold and platinum targets, with intensities up to ~1.9 × 10(21) W.cm(-2) and pulse durations as short as ~130 fs. Positron to electron (e+/e-) ratios >15% were observed for many thick disk and rod targets, with the highest e+/e- ratio reaching ~50% for a Pt rod. The inferred pair yield was ~ few ×10(10) with emerging pair density reaching ~10(15)/cm(3) so that the pair skin depth becomes < pair jet transverse size. These results represent major milestones towards the goal of creating a significant quantity of dense pair-dominated plasmas with e+/e- approaching 100% and pair skin depth ≪ pair plasma size, which will have wide-ranging applications to astrophysics and fundamental physics.


A Prospective Study on Skin-Sparing Mastectomy for Immediate Breast Reconstruction with Latissimus Dorsi Flap After Neoadjuvant Chemotherapy and Radiotherapy in Invasive Breast Carcinoma.
Skin-sparing mastectomy (SSM) with immediate breast reconstruction (IBR) is increasingly used in invasive breast cancer. However, adjuvant chemotherapy (CT) and radiotherapy (RT) can increase the rate of local complications. The aim of this study was to assess the morbidity of SSM-IBR after neoadjuvant CT and RT. A French prospective pilot study of women aged 18-75 years with invasive breast cancer requiring mastectomy after CT and RT. Reconstruction was performed using autologous latissimus dorsi flap with or without prosthesis. The primary endpoint was the skin necrosis rate within 6 months, while secondary endpoints included pathological complete response rate (pCR) and global morbidity. Among 94 patients included in this study, 83 were analyzed (mean age 45.2 ± 9.5 years, T1 23.6 %, T2 55.6 %, T3 18.1 %). All but one patient received anthracyclines and taxanes, and all patients received RT (49.3 ± 5.2 Gy) before SSM-IBR. Prostheses were used for IBR in 32 patients (mean volume 256 ± 73 mm(3)). Five patients had necrosis (≤2 cm(2), 2-10 cm(2) and >10 cm(2), in three, one, and one cases, respectively), and they all recovered without revision surgery. Among 50 patients who underwent upfront mastectomy, 36 % achieved pCR. SSM-IBR performed after CT and RT is safe, with an acceptable local morbidity rate. Long-term data are needed to evaluate recurrence rates.


Minimally Invasive Fracture Repair of the Tibia and Fibula.
Fractures of the tibia and fibula are common in dogs and cats and occur most commonly as a result of substantial trauma. Tibial fractures are particularly amenable to treatment using minimally invasive fracture repair (MIFR) techniques that preserve blood supply to comminuted fracture fragments, accelerating bone callus production and speeding fracture healing. Treatment of tibial fractures using MIFR techniques has been found to reduce surgical time, reduce the time for fracture healing, and to decrease patient morbidity, while at the same time reducing complications compared with traditional open reduction and internal fixation.


Novel application of the 2-piece orthodontic C-implant for temporary crown restoration after orthodontic treatment.
This article reports the use of an orthodontic mini-implant for a temporary crown restoration in a small edentulous space after limited orthodontic treatment. Two clinical cases are presented: a 23-year-old woman and a 14-year-old boy. In the adult patient, a 2-piece orthodontic C-implant (Cimplant, Seoul, Korea) was placed in a 3-mm wide edentulous space to build up a temporary crown restoration after a short orthodontic treatment to regain space for a missing mandibular right permanent lateral incisor. In the boy, a C-implant was placed in the space resulting from an avulsed maxillary right permanent lateral incisor to prevent aggressive alveolar bone resorption after dental trauma. Both patients were followed for more than 4 years of retention to evaluate the stability of the temporary crown restoration built up on the orthodontic mini-implants. Both patients had successful long-term results, confirmed by clinical and radiographic examinations. Both were pleased with the results and plan to retain the orthodontic mini-implant temporary crown restoration until they are ready for a permanent restoration later. A 2-piece orthodontic C-implant system can be used to maintain edentulous space after active orthodontic treatment.


Morphological variability in Fasciola hepatica eggs in ruminants, rodents and lagomorphs.
The length and width of 1297 Fasciola hepatica eggs shed in cattle hosts, 337 in sheep and 199 in nutria, were measured from several parts of France. The data were compared with those obtained from other studies in Spain, France (where rats were also investigated), Germany and the Netherlands. One way analysis of variance and discriminant analysis were used to assess differences between host origins. The distribution of length and width of eggs were analysed using skewness and kurtosis Fisher coefficients. The eggs recovered from sheep, cattle, rodents and lagomorphs were different in size: the eggs found in rodents (length L x width W in microm: 8592) and lagomorphs (L x W in microm: 9100) were smaller than those found in sheep and cattle (L x W in microm: 10,000). These morphological differences in F. hepatica eggs were host-induced in rats (L x W in microM: 9709 in cattle to 8949 in rats) and rabbits (L x W in microm: 9709 in cattle to 8432 in rabbits). These differences in size of eggs might correspond to their being less able to develop into miracidia in less frequent hosts such as rodents and rabbits.


Hypertension and SNP genotyping in antihypertensive treatment.
Hypertension is prevalent, affecting approx 20--25% of the adult population in the Western world. Primary hypertension is a multifactorial, complex disorder where many genes and genetic variants are assumed to interact with environmental factors in order to produce the specific blood pressure level for a given individual. Family and twin studies show that between 30 and 60% of blood pressure variation is determined by genetic factors. Monogenic disorders of hypertension are rare and do not explain blood pressure variability in the population at large. Obvious candidate genes for the study of hypertension are those that encode components of a blood pressure regulating system targeted by an antihypertensive drug, or those that are involved in counter-regulatory systems. In this review, we give a brief pathophysiological background to hypertension and the rational behind utilizing SNP genotyping in the study of hypertension and the antihypertensive response to treatment. We also discuss some of the novel results of pharmacodynamic studies in antihypertensive treatment, an area in its infancy.


[Therapy effects of testosterone on the recovery of bone defects].
Androgens have proliferative effects on osteoblasts and increase fracture healing by systemic and local stimulation of bone formation. The aim of the present study was to evaluate if the systemic stimulation by androgens leads to increased bone-defect healing. 1.5-mm trepanation defects were created in the femoral diaphysis of 30 Sprague-Dawley rats. 10 animals were used as untreated controls and 10 animals per group were treated by intramuscular injection of 1 or 10 mg dihydrotestosterone two days prior to surgery. After 14 days the samples were explanted and examined by macroscopy, histology and histomorphometry. All animals were included into the study and were analysed. Clinical observation showed no complications. Macroscopic examination and histology showed no significant differences. All defects were filled with trabecular bone in direct contact to the surrounding bone. Histomorphometry showed a significantly decreased bone content in the controls in comparison to both therapy groups, while the therapy groups showed no significant differences between each other. The stimulation of healing of bone defects with androgens leads to a significantly higher bone content inside the defects. In clinical application, androgens may be a possibility to increase bone formation, especially in elderly patients. Furthermore, it may be possible to shorten postoperative rehabilitation because of the effects of androgens on muscles.


Calcium availability from whey mineral residues increased by hydrogen citrate.
Insoluble mineral residues from whey processing dominated by hydroxyapatite and calcium hydrogen phosphate were found to dissolve isothermally in aqueous sodium hydrogen citrate. Dissolution occurred spontaneously and the resultant homogeneous solutions were found to be supersaturated solutions in both calcium citrate and calcium hydrogen phosphate. Supersaturation was investigated by visual inspection combined with turbidity measurements and analyses of calcium and phosphorous by ICP. The maximal supersaturation was found to be proportional to total hydrogen citrate concentration. For 0.2 M hydrogen citrate, maximum calcium concentration was achieved in the first hours of dissolution resulting in the supersaturation of calcium hydrogen phosphate with a factor of 10. Calcium citrate rather than calcium hydrogen phosphate precipitated from the supersaturated solutions and the time elapsing before precipitation began, increased with increasing concentrations of excess of hydrogen citrate. This lag phase for precipitation ranged from several hours for 0.2 M hydrogen citrate to more than a day for higher hydrogen citrate concentrations, for which the solutions were saturated in calcium hydrogen phosphate and became supersaturated only in calcium citrate due to the strong binding of calcium by citrate. The appearance and decay of supersaturation was kinetically studied in order to provide the background for future exploration of whey minerals in functional foods for improved calcium nutrition.


Enhanced production of cellulases byCellulomonas strains grown on different cellulosic residues.
Cellulomonas strains consumed commercial cellulose, cellulosic residues, xylan, cellobiose and carboxymethyl cellulose (CMC) as carbon sources in liquid culture, the growth being the most on cellobiose medium. All three components of the cellulase complex ofCellulomonas were produced when the organisms utilized all substrates as sole carbon and energy sources. The filter-paper cellulase (FPase) and endo-glucanase (CMCase) activities were higher in media containing alpha-cellulose and cellulosic residues than in media containing CMC, cellobiose, and xylan. Cell-free supernatants of all organisms exhibited greater CMC hydrolyzing activity than filter paper and beta-glucoside hydrolyzing activities. All strains synthesized beta-glucosidase maximally on cellobiose followed by commercial cellulose and cellulosic residues.C. biazotea produced the highest FPase and CMCase activity during growth on alpha-cellulose. It was followed byC. flavigena, C. cellasea, andC. fimi. Endo-glucanase and FPase from all organisms were secreted into the medium; 10-13 % became adsorbed on the surface of the insoluble substrates and could be successfully eluted using Tween 80. beta-Glucosidase was located in cell extracts from all organisms.C. biazotea produced FPase and beta-glucosidase activities several-fold greater than those produced by many other strains ofCellulomonas and some other cellulolytic bacteria and fungi.


Lianqinjiedu decoction attenuates LPS-induced inflammation and acute lung injury in rats via TLR4/NF-κB pathway.
Acute lung injury (ALI) and its severe form acute respiratory distress syndrome remain the leading cause of morbidity and mortality. LianQinJieDu (LQJD), which is a traditional Chinese medicine, has been clinically used for antiviral drug. The present study investigated whether Lianqinjiedu(LQJD) ameliorates lipopolysaccharide(LPS)-induced acute lung injury in rats and aimed to determine the anti-inflammatory effects of LQJD. Rat model with ALI induced by intraperitoneal injection of LPS was treated by oral administration of LQJD. The recruitment of body temperature and the histopathology of lung tissue from all groups were evaluated to grade the severity of the inflammation. The inflammatory cytokine levels, including tumor necrosis factor-α (TNF-α)and interleukin-6 (IL-6), were examined by ELISA assay, and the TLR4 and NF-κBp65 expression levels were evaluated by Real time-PCR and western blotting. It was observed that LQJD reduced the LPS-induced body temperature, inflammatory cytokines level, and lung injuries, and blocked the activation of TLR4/NF-κBp65 signaling in lung tissue. This study demonstrates that LQJD has a protective effect on LPS-induced inflammatory rats through the signaling pathway of TLR4 and NF-κBp65.


Modernizing Medical Research to Benefit People and Animals.
In the context of widespread public and political concern around the use of animals in research, we sought to examine the scientific, ethical and economic arguments around the replacement of animals with New Approach Methodologies (NAMs) and to situate this within a regulatory context. We also analyzed the extent to which animal replacement aligns with British public and policymakers' priorities and explored global progress towards this outcome. The global context is especially relevant given the international nature of regulatory guidance on the safety testing of new medicines. We used a range of evidence to analyze this area, including scientific papers; expert economic analysis; public opinion polls and the Hansard of the UK Parliament. We found evidence indicating that replacing animals with NAMs would benefit animal welfare, public health and the economy. The majority of the British public is in favor of efforts to replace animals and focusing on this area would help to support the British Government's current policy priorities. We believe that this evidence underlines the need for strong action from policymakers to accelerate the transition from animal experiments to NAMs. The specific measure we suggest is to introduce a new ministerial position to coordinate and accelerate the replacement of animals with NAMs.


A 3D-printed orthopedic implant with dual-effect synergy based on MoS2 and hydroxyapatite nanoparticles for tumor therapy and bone regeneration.
Treatments for malignant bone tumors are urgently needed to be developed due to the dilemma of precise resection of tumor tissue and subsequent bone defects. Although polyether-ether-ketone (PEEK) has widely attracted attention in the orthopedic field, its bioinertness and poor osteogenic properties significantly restrict its applications in bone tumor treatment. To tackle the daunting issue, we use a hydrothermal technique to fabricate novel PEEK scaffolds modified with molybdenum disulfide (MoS2) nanosheets and hydroxyapatite (HA) nanoparticles. Our dual-effect synergistic PEEK scaffolds exhibit perfect photothermal therapeutic (PTT) property dependent on molybdous ion (Mo2+) concentration and laser power density, superior to conventional PEEK scaffolds. Under near-infrared (NIR) irradiation, the viability of MG63 osteosarcoma cells is significantly reduced by modified PEEK scaffolds, indicating a tumor-killing potential in vitro. Furthermore, the incorporation of HA nanoparticles on the surface of PEEK bolsters proliferation and adherence of MC3T3-E1 cells, boosting mineralization for further bone defect repair. The results of micro-computed tomography (micro-CT) and histological analysis of 4-week treated rat femora demonstrate the preeminent photothermal and osteogenesis capacity of 3D-printed modified scaffolds in vivo. In conclusion, the dual-effect synergistic orthopedic implant with photothermal anticancer property and osteogenic induction activity strikes a balance between tumor treatment and bone development promotion, offering a promising future therapeutic option.


Misleading image of mechanical valve leaflet by transesophageal echocardiography.
Although bileaflet prosthetic valve function is commonly assessed by means of transesophageal echocardiography (TEE) during surgery, the author reports that the leaflet image is not a real image but an artifact. As the depth of the transducer is altered, the leaflet image is gradually skewed in relation to the plane of the prosthetic valve ring. The leaflet-like image consistently overlaps the line that is drawn from the transducer position to the atrial side edge of the leaflet, indicating that this image is caused by reverberations. Three-dimensional TEE shows that the leaflet image is not semilunar but is elongated towards the left ventricle and unusually tilted. As viewed from the ventricular side, the ring image is elongated and forms a cylinder-like image in the left ventricle, and the leaflets appear to be opening and closing at the bottom of this cylinder. Therefore, TEE assessment of leaflets in the open position can be misleading.


Fighting arboviral diseases: low toxicity on mammalian cells, dengue growth inhibition (in vitro), and mosquitocidal activity of Centroceras clavulatum-synthesized silver nanoparticles.
Dengue is a mosquito-borne viral disease that has rapidly spread in all regions of the world in recent years. Female mosquitoes, mainly Aedes aegypti, transmit dengue. Approximately 3,900 million people, in 128 countries, are at risk of dengue infection. Recently, a focus has been provided on the potential of green-synthesized nanoparticles as inhibitors of the production of dengue viral envelope (E) protein in Vero cells and downregulators of the expression of dengue viral E gene. Algae are an outstanding reservoir of novel compounds, which may help in the fight against mosquito-borne diseases. In this research, silver nanoparticles (AgNP) were rapidly synthesized using a cheap extract of the alga Centroceras clavulatum. AgNP were characterized by UV–vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). In mosquitocidal assays, LC50 values of C. clavulatum extract against A. aegypti larvae and pupae were 269.361 ppm (larva I), 309.698 ppm (larva II), 348.325 ppm (larva III), 387.637 ppm (larva IV), and 446.262 ppm (pupa). C. clavulatum extract also exhibited moderate antioxidant activity, both in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging assays. LC50 values of C. clavulatum-synthesized AgNP were 21.460 ppm (larva I), 23.579 ppm (larva II), 25.912 ppm (larva III), 29.155 ppm (larva IV), and 33.877 ppm (pupa). Furthermore, C. clavulatum-synthesized AgNP inhibited dengue (serotype dengue virus type-2 (DEN-2)) viral replication in Vero cells. Notably, 50 μg/ml of green-synthesized AgNP showed no cytotoxicity on Vero cells while reduced DEN-2 viral growth of more than 80%; 12.5 μg/ml inhibited viral growth of more than 50%. Cellular internalization assays highlighted that untreated infected cells showed high intensity of fluorescence emission, which denotes high level of viral internalization. Conversely, AgNP-treated infected cells showed reduced levels of fluorescence, failing to show significant viral load. Overall, our study showed that alga-mediated synthesis of metal nanoparticles may be considered to develop newer, safer, and cheap tools in the fight against the dengue virus, serotype DEN-2, and its vector A. aegypti, with little cytotoxicity on mammalian cells.


Study on the specificity of Shore's method for the determination of histamine in various tissues.
Specificity of Shore's method for the histamine determination was investigated by examining the fluorescence spectrum of the extract from rat gastric mucosa, biopsy specimen of human gastric mucosa, human gastric juice and human whole blood. An almost identical spectrum to that of pure histamine was obtained with the extract from rat gastric mucosa and human whole blood, whereas the spectrum with the extract of human gastric biopsy specimen and human gastric juice was different from that of histamine. By means of high-performance liquid chromatography, an approximately three times more concentrated extract from human gastric mucosa gave a distinct peak of histamine while a hundred times concentrated gastric juice gave no measurable peak of histamine. Fluorescence spectrum of the substances which might be extracted with histamine was examined. The ratio of the fluorescence of histidine to that of equimolar concentration of histamine at the wave length for histamine determination was 4.62%. From the above results, it has been concluded that Shore's method is useful for the determination of histamine contents in the gastric mucosa and whole blood if approximately 5% contamination with histidine is taken into consideration.


Weather changes and pain: perceived influence of local climate on pain complaint in chronic pain patients.
Patients with chronic pain frequently report that changes in the weather influence their pain. This study investigated differences in the perceived influence of weather on pain among 558 chronic pain patients living in 4 cities (San Diego, California; Nashville, Tennessee; Worcester, Massachusetts; and Boston, Massachusetts) in the United States. Local climatologic data for each city were obtained from the National Climatic Data Center. All patients completed a weather questionnaire, and the information they provided was compared with demographic and weather variables. The majority of all patients believed that changes in the weather affected their pain. Pain patients who were younger and who had arthritis reported the most sensitivity to changes in weather. Weather sensitivity was unrelated to all other demographic variables and to geographic region. Cold and damp conditions were considered to influence pain the most. However, the perceived effect of weather on pain was not found to be related to regional climate. Thus, the belief that pain is worsened by living in a colder climate was not supported. An equilibrium theory of weather changes and pain is discussed. Further investigations are needed to identify the mechanisms involved in the effects of weather changes on pain.


Acute renal failure and metabolic disturbances in the short bowel syndrome.
Short bowel syndrome (SBS) describes a malabsorptive state caused by extensive loss of small intestinal length. To improve understanding of the metabolic complications of SBS. Observational study of five patients with SBS who presented with acute renal failure. Acute renal failure in our patients was predominantly due to salt and fluid depletion, and sepsis. Electrolyte imbalance was a major cause of morbidity. Metabolic acidosis was seen in three patients, and may arise from excessive gastrointestinal bicarbonate loss, compounded by impaired renal homeostasis. Our patients also manifested disturbances of calcium and magnesium homeostasis. Patients with SBS are at high risk of renal failure. Prevention of this complication requires close monitoring and the maintenance of sodium homeostasis through increased intake and measures to reduce loss (e.g. anti-motility agents and large bowel re-anastomosis), and calcium, magnesium and vitamin D supplementation.


Pelvic organ prolapse and urinary incontinence in nulliparous women at the United States Military Academy.
The objective of this study was to evaluate both baseline pelvic support and incontinence in relation to physical activity in nulliparous college women. Participants were examined using the pelvic organ prolapse and quantification system (POP-Q) and completed a questionnaire. Women with stage 0 prolapse and any other stage were compared. Potential risk factors and levels of physcial activity were analyzed using the chi-square test. We evaluated 144 women. Fifty percent had stage 0 support and 50% had stage I or II. Nineteen percent of participants reported incontinence. No risk factors for prolapse were identified, however running was associated with incontinence. Forty-six percent of physically active nulliparous college students had stage I pelvic support without identifiable risk factors. Stage I and II prolapse represent normal support.


Structural competency curriculum in health sciences education: a scoping review protocol.
This scoping review aims to explore existing literature related to structural competency and how this concept is being implemented and evaluated in health sciences programs. The secondary aim is to examine and summarize any documented outcomes related to structural competency training. Structural competency is a concept that was introduced in 2014 to train pre-health and health professionals to understand the broader structures that influence health outcomes. Studies have shown structural competency training is beneficial to health science students. To address health outcomes at the population level, students should collaborate with other disciplines to address the larger structures that influence health. This scoping review will consider studies that include health science programs that implemented or evaluated structural competency training for undergraduate students, graduate students, and postgraduate trainees. The key databases to be searched include MEDLINE, CINAHL, Scopus, Embase, Europe PubMed Central, PsycINFO, and ERIC. The search for unpublished studies will include ProQuest Dissertations and Theses, PapersFirst, and OpenGrey. Studies conducted in English, in any year, setting, or geographical location will be included. Two independent reviewers will perform retrieval of full-text studies and data extraction. The results will be presented in diagrammatic or tabular format with a narrative summary.


Human U3 small nucleolar RNA genes are localized to the nucleoplasm.
U3 RNA, an abundant, conserved, capped, small RNA localized to the nucleolar compartment of eukaryotic cells, its implicated in the processing of pre-ribosomal RNA. The genes for U1 and U2 snRNAs (small nuclear RNAs) are clustered and present in the nucleoplasmic DNA; however, the localization of U3 snRNA genes is not known. DNAs, isolated from HeLa cell nuclei and nucleoli, were hybridized with labeled probes corresponding to the 5'-flanking and the coding regions of the human U3 snRNA gene. The intensity of signals obtained with both the probes were 5-6 fold greater in nuclear DNA, compared to nucleolar DNA. With ribosomal gene probe, the nucleolar DNA had sixfold more intense signal than nuclear DNA. These results indicate that genes for U3 snRNA are in the nucleoplasm. Therefore, U3 snRNA, like 5S ribosomal RNA, appears to be synthesized in the nucleoplasm and transported to the nucleolus.


Influence of GABA-B Agonist Baclofen on Capsaicin-Induced Excitation of Secondary Peristalsis in Humans.
Esophageal instillation of capsaicin enhances secondary peristalsis, but the γ-aminobutyric acid receptor type B (GABA-B) agonist baclofen inhibits secondary peristalsis. This study aimed to investigate whether baclofen could influence heartburn perception and secondary peristalsis subsequent to capsaicin infusion in healthy adults. Secondary peristalsis was performed by slow and rapid mid-esophagus air injections in 15 healthy subjects. Two different sessions including esophageal infusion of capsaicin-containing red pepper sauce (0.84 mg) following pre-treatment with placebo or baclofen were randomly performed to test the effects on heartburn perception and secondary peristalsis. The intensity of heartburn symptom subsequent to capsaicin infusion was significantly greater after pre-treatment of baclofen as compared with the placebo (P=0.03). Baclofen significantly increased the threshold volume of secondary peristalsis to slow air injections subsequent to esophageal capsaicin infusion (P<0.001). Baclofen significantly increased the threshold volume of secondary peristalsis to rapid air injections subsequent to esophageal capsaicin infusion (P<0.01). The frequency of secondary peristalsis subsequent to capsaicin infusion was significantly decreased with baclofen as compared with the placebo (P<0.002). Baclofen had no effect on any of the peristaltic parameters of secondary peristalsis subsequent to capsaicin infusion. The GABA-B agonist baclofen appears to attenuate the esophagus to capsaicin-induced excitation of secondary peristalsis in healthy adults. Our study suggests the inhibitory modulation for GABA-B receptors on capsaicin-sensitive afferents mediating secondary peristalsis in human esophagus.


Small mammal seed consumption in the Karoo, South Africa: further evidence for divergence in desert biotic processes.
Annual seed consumption by a small mammal community in the semi-arid Karoo, South Africa, was calculated using population, biomass and dietary estimates and published estimates of field metabolic rate. The community comprised a macroscelid elephant shrew Macroscelides proboscideus, and two rodents Gerbillurus paeba and Desmodillus auricularis. Only G. paeba consumed seed during the study, and then in low amounts (annual mean = 0.4% of diet, insects = 53%, herbage = 47%), with M. proboscideus and D. auriocularis consuming mainly insects (88%) and herbage (90%), respectively. Energy requirements for the G. paeba population averaged 568 kJ ha-1 day-1. Total seed consumption was estimated to be ≈ 140 g ha-1, or 155 000 seeds ha-1 which represents ≈0.5% of the annual seed production for this site. These levels of granivory by small mammals are significantly lower than those recorded for North American deserts, and raises the question as to why granivory varies between these systems. These findings also refute the hypothesis that as a result of the harshness and similarity of physical conditions in deserts, the properties of desert communities are convergent.


The effect of Swedish massage on pain in rheumatoid arthritis patients: A randomized controlled trial.
Joint pain is one of the most common symptoms in rheumatoid arthritis patients and require medical attention. The purpose of this study was to assess the effects of Swedish massage on pain and painkiller consumption in rheumatoid arthritis patients. A total of 60 patients participated in the experiment, with half assigned to the control group (n = 30) and half to the experimental (n = 30) group using the block randomization method. On patients in the experimental group, a 30-min Swedish massage was performed regularly for eight weeks: twice a week for the first four weeks, and three times a week for the last four weeks. The control group received routine care. The visual analogue scale-pain was used to measure pain in the two groups at three points of time: before the beginning of the experiment, immediately after the last session, and one month after the last session of the intervention. The analysis of covariance showed that there were significant differences between the two groups' mean scores of pain and painkiller consumption immediately after and one month after the last session of the intervention (p = 0.01). Furthermore, in the experimental group, the mean scores of pain and painkiller consumption decreased over the three points of time (p < 0.05). Swedish massage can be effective in reducing pain and the need to use painkillers in rheumatoid arthritis patients.


Performance of the SF-36 health survey in screening for depressive and anxiety disorders in an elderly female Swedish population.
To assess the sensitivity, specificity and predictive validity of suggested cut-off scores in the SF-36 mental health (MH) and mental component summary (MCS) in screening for depressive and anxiety disorders in a population sample of older Swedish women. The sample comprised 586 randomly selected females aged 70-84 years who took part in an in-depth psychiatric examination. This provided the 'gold standard' against which the usefulness of SF-36 recommended thresholds for screening for depressive and anxiety disorders in older Swedish women was examined. Based on DSM-III-R criteria, 69 women (12%) were diagnosed with depression (major depression, dysthymia and/or depression NOS) and 49 (8%) with generalised anxiety and panic disorders. The previously recommended MH and MCS cut-offs (i.e. 52 and 42) gave a specificity for diagnosis of depression of 92 and 82% and sensitivity of 58 and 71%, respectively. Both the MH and MCS were good predictors of depressive disorders but poor predictors of anxiety disorders. The study supports the predictive validity of suggested SF-36 MH and MCS cut-off scores in screening for depressive disorder but not for anxiety disorder in older women in Sweden.


Osteoporosis in the elderly.
Osteoporosis is predominantly a condition of the elderly with a consequent increase in bone fragility and susceptibility to fracture. A number of clinical as well as biological studies have been pivotal in providing us with an understanding of the pathophysiology of this condition. This article discusses the current concepts of age-related osteoporosis.


Electrophoretic mobility of duplex DNA cross-linked by mechlorethamine at a cytosine-cytosine mismatch pair.
The common nitrogen mustard, mechlorethamine, can form a covalent cross-link between the two bases of a cytosine-cytosine mismatch pair within a DNA duplex. The cross-linked species can be readily separated from DNA monoadducts and unreacted strands using denaturing polyacrylamide gel electrophoresis. Here, using DNA 19 mer duplexes that are mechlorethamine cross-linked at a C(4)-C(35), C(7)-C(32), C(10)-C(29), or C(13)-C(26) mismatch pair, we show that the denaturing polyacrylamide gel electrophoresis mobility of the cross-linked species is particularly sensitive to the proximity of the C-C cross-link to the duplex end. Species that are cross-linked at a C(4)-C(35) mismatch have greater mobilities than those cross-linked at C(7)-C(32) or C(13)-C(26), and the species with a central C(10)-C(29) cross-link have the lowest mobility. The mobility is also dependent on the proximity of the cross-link to a 5'-(32)P-phosphate or a 5'-fluorescein label. We interpret these results in terms of the conformational properties of the cross-linked species in the denaturing gel. The results are consistent with the retention of partial duplex character at the end proximal to the cross-link, with an influence on the mobility of the GC/AT ratio proximal to the cross-link and at the duplex end, and a small but discernible effect of the label.


[Changes in the orientation of the smooth-muscle cells of the tunica media from major arteries under constant lengthwise stretching in situ].
It has been shown that changes in the orientation of arterial smooth muscle cells during a constant longitudinal stretching of the artery in vivo are not similar in different sections of the stretching zone. Cells in the proximal and distal sections keep their orientation but this orientation differs from that of smooth muscle cells in the control arteries. Cells in the central part of the stretching region lose their definite orientation to settle randomly.


The "rib-like" technique for surgical treatment of sternal tumors: lessons learned from 101 consecutive cases.
Sternal tumors represent a rare subgroup of chest wall neoplasms in which indication, surgical issues, and long-term results are rarely reported. Thus, in this study we reevaluated our experience in sternal replacement from a series of 101 consecutive cases during the last 30 years. Clinical records of patients who underwent sternal resection between January 1980 and December 2008 were reviewed. The technique of reconstruction after sternectomy varied over time, including mesh replacement in 52 patients (group A), rigid prosthesis in 27 patients (group B), and the "rib-like" technique, a semi-rigid tridimensional prosthesis reproducing the shape of native ribs, in 22 patients (group C). Postoperative outcomes and long-term survival were analyzed. Of 101 patients, 42 underwent resection for primary chest wall tumors, 30 for breast cancer, 15 for locally advanced tumors, 11 for metastatic disease, and 3 for benign disease. One patient died postoperatively. The overall major complications rate was similar between groups. Local infection required prosthetic removal in 7 patients of groups A and B (9%). No infection occurred in group C (p = 0.02). Median survival exceeded 60 months for primary sternal tumors and 22 months for other cancer (p = 0.01). The worst survival was recorded in radioinduced sarcoma (17 months) and in patients who underwent previous resection before salvage sternectomy (18 months). Results from this study showed that an adequate sternal resection should be done at the first operation and that improving prosthetic integration with surrounding tissues may reduce the local complication rate.


Highly Potent MRI Contrast Agent Displaying Outstanding Sensitivity to Zinc Ions.
Zinc ions play an important role in numerous crucial biological processes in the human body. The ability to image the function of Zn2+ would be a significant asset to biomedical research for monitoring various physiopathologies dependent on its fate. To this end, we developed a novel Gd3+ chelate that can selectively recognize Zn2+ over other abundant endogenous metal ions and alter its paramagnetic properties. More specifically, this lanthanide chelate displayed an extraordinary increase in longitudinal relaxivity (r1 ) of over 400 % upon interaction with Zn2+ at 7 T and 25 °C, which is the greatest r1 enhancement observed for any of the metal ion-responsive Gd-based complexes at high magnetic field. A "turn-on" mechanism responsible for these massive changes was confirmed through NMR and luminescence lifetime studies on a 13 C-labeled Eu3+ analogue. This molecular platform represents a new momentum in developing highly suitable magnetic resonance imaging contrast agents for functional molecular imaging studies of Zn2+ .


Spermidine determines the sensitivity to the calmodulin antagonist, chlorpromazine, for the circadian conidiation rhythm but not for the mycelial growth in Neurospora crassa.
The gene that suppresses the phenotype of the cpz-2 mutation, which results in changing the sensitivity to chlorpromazine in relation to mycelial growth and circadian rhythms, was cloned in Neurospora crassa. This gene is not the cpz-2 gene itself but rather is identical to the spe-3 gene that encodes spermidine synthase in Neurospora. The intracellular content of spermidine was lowered in the cpz-2 strain compared to that of the wild-type strain. By integration of the spe-3 gene or by the addition of spermidine into culture medium, the temperature sensitivity of mycelial growth was lost and the conidiation rhythm became sensitive to chlorpromazine in the cpz-2 strain, as was observed in the wild-type strain, but the hypersensitivity of mycelial growth on chlorpromazine in the cpz-2 strain was not affected. Therefore, it appears that spermidine determines only the sensitivity of the conidiation rhythm to chlorpromazine.


Is the cost of adult living donor liver transplantation higher than deceased donor liver transplantation?
An important long-term consideration for living-donor liver transplantation (LDLT) is the expense compared with cadaveric-liver transplantation. LDLT is a more complex procedure than cadaveric transplantation and the cost of donor evaluation, donor surgery, and postoperative donor care must be included in a cost analysis for LDLT. In this study, we compare the comprehensive cost of LDLT with that of cadaveric-liver transplantation. All costs for medical services provided at our institution were recorded for 24 LDLT and 43 cadaveric recipients with greater than 1 year follow-up transplanted between August 1997 and April 2000. The donor costs include donors evaluated and rejected, donors evaluated and accepted, donor right hepatectomy costs, and donor follow-up costs (365 days postdonation). LDLT and cadaveric recipient costs include medical care 90 days pre-LDLT, recipient transplant costs, and recipient follow-up costs (365 days posttransplant) including retransplantation. Cost is expressed as an arbitrary cost unit (CU) that is a value between $500 to $1,500. Total LDLT costs (evaluations of rejected donors + evaluations of accepted donors + donor hepatectomy + donor follow-up care for 1 year + pretransplant recipient care [90 days pretransplant] + recipient transplantation + recipient 1-year posttransplant care) = 162.7 CU. Total mean cadaveric transplant costs (pretransplant recipient care [90 days pretransplant] + recipient transplantation [including organ acquisition cost] + recipient 1-year posttransplant care)=134.5 CU, (P = ns). The total comprehensive cost of LDLT is 21% higher than cadaveric transplantation, although this difference is not significant. (Transplantation 2003;75:473-476.)


Cross contamination control and the dental handpiece.
The issue of heat sterilization of handpieces for every patient every time evokes visions of higher cost, damage to handpiece sheaths and turbines, and increased staff involvement. The introduction of fast turn-around steam autoclaves reduces the number of handpieces required and helps lower costs. The damage can be contained by using high-quality handpieces and by maintaining them properly. Staff involvement time can be reduced through the use of handpiece scrubbers, handpiece flush systems, and simple, adequate maintenance standards. Because of the discovery that biofilms contribute to the microbial contamination of dental unit water lines, the need for a clean water system is apparent because it will further reduce the potential danger of cross contamination.


Outcomes of Using Otoendoscopy During Surgery for Cholesteatoma.
To determine the impact of using otoendoscopy at the time of primary surgery of cholesteatoma in identifying hidden "cholesteatoma remnant". Study was prospective study. Setting was University tertiary care hospital. One hundred fifty, patients diagnosed clinically and by CT as having cholesteatoma, have been operated. 64 patients operated by using canal up technique and 86 patients operated by using canal down technique. Once all visible cholesteatoma was removed with standard microscopic techniques, otoendoscopy was utilized in every patient to identify any hidden "cholesteatoma remnant". Despite apparent total microscopic eradication of cholesteatoma of the operated cases, otoendoscopy at time of primary surgery revealed an overall incidence of hidden cholesteatoma remnants of 18%. The incidence of hidden cholesteatoma remnants identified by otoendoscopy was 23% in the canal up group and 14% in the canal down group. Otoendoscopy should be used as an adjunct with standard microscopic technique to identify hidden cholesteatoma remnants during surgery of cholesteatoma.


Effects of orbital prefrontal cortex dopamine depletion on inter-temporal choice: a quantitative analysis.
Lesions of the orbital prefrontal cortex (OPFC) can cause pathologically impulsive behaviour in humans. Inter-temporal choice behaviour (choice between reinforcers differing in size and delay) has been proposed as a model of "impulsive choice" in animals. We recently found that destruction of the OPFC disrupted inter-temporal choice in rats. It is not known whether the dopaminergic projection to the OPFC contributes to the regulation of inter-temporal choice. A quantitative method was used to compare inter-temporal choice in rats whose OPFC had been depleted of dopamine with that of sham-lesioned control rats. Under halothane anaesthesia, rats received injections of 6-hydroxydopamine into the OPFC (2 microg microl(-1), 0.5 microl, two injections in each hemisphere), or sham lesions (injections of the vehicle). They were trained to press two levers (A and B) for sucrose reinforcement (0.6 M) in discrete-trials schedules. In free-choice trials, a press on A resulted in delivery of 50 microl of the sucrose solution after a delay dA; a press on B resulted in delivery of 100 microl of the same solution after a delay dB. dB was increased progressively across successive blocks of six trials in each session, while dA was manipulated systematically across phases of the experiment. The indifference delay, dB(50) (value of dB corresponding to 50% choice of B) was estimated for each rat in each phase. Linear functions of dB(50) versus dA were derived, and the parameters of the function compared between the groups. Concentrations of monoamines in the OPFC were determined by high-performance liquid chromatography at the end of the experiment. In both groups, dB(50) increased linearly with dA (r2>0.9 in each case). The slope of the function was significantly steeper in the lesioned group than the sham-lesioned group, whereas the intercept did not differ significantly between the groups. When delays of 4 or 8 s were imposed on the smaller reinforcer, the lesioned rats showed greater tolerance of delay to the larger reinforcer (i.e. they exhibited longer values of dB(50)) than the sham-lesioned rats. Dopamine, noradrenaline and 5-hydroxytryptamine levels in the OPFC of the lesioned group were 20, 75 and 98% of those of the sham-lesioned group. The results indicate that dopaminergic afferents to the OPFC contribute to the regulation of inter-temporal choice behaviour due to their role in determining organisms' sensitivity both to reinforcer size and to delay of reinforcement.


Variations in life history characteristics ofDaphnia pulex fed different algal species.
Groups of individualDaphnia pulex were fed one of three algae (Pediastrum duplex, Chlamydomonas monadina, orMelosira ambigua) from age one day until death and their reproductive characteristics were monitored.Daphnia which were fedMelosira matured later, lived longer and produced more but smaller broods thanDaphnia which were fedPediastrum orChlamydomonas. Ro values did not differ among the groups but the fertility pattern was variable which is suggested to be of adaptive significance resulting from fluctuations of different food quality algae.


An ovarian independent population of uterine estrogen receptors.
Estrogen receptor levels in uteri from ovariectomized mice varied markedly with time after surgery; these changes were not due to nuclear translocation. Receptor cyclicity was abolished in ovariectomized-adrenalectomized mice, and receptor levels remained low. This indicates that the adrenals significantly influenced uterine estrogen receptor levels. However, these adrenal-mediated changes did not alter uterine responsiveness ot estrogen stimulation.


Dermatology on the global stage: The role of dermatologists in international health advocacy and COVID-19 research.
Over the last decade, there has been a surge in interest and funding for global health dermatology. Skin conditions are now recognized as the fourth leading cause of nonfatal disease burden worldwide in disability-adjusted life years. Dermatologists are uniquely positioned within global health because skin conditions are often the presenting sign of severe illnesses, such as neglected tropical diseases and COVID-19. We review four major areas of work by dermatologists within global health: i) characterization of global burden of skin disease, ii) advocacy for dermatologic therapies on the World Health Organization's Model List of Essential Medicines, iii) advancements in global programming for skin-related tropical diseases, and iv) the role of dermatologists during the COVID-19 pandemic. For each area of work, the significance and impact on the health of women and girls is briefly highlighted. Dermatologists have led the efforts to quantify and evaluate the global burden of skin disease, the burden of which is disproportionately shared by women. The dermatology community has also championed global efforts to eliminate skin-related neglected tropical diseases, such as scabies. Through national and international policy advocacy, dermatologists have pushed for more dermatologic therapies in the World Health Organization's Model List of Essential Medicines, helping to secure better care for patients with skin disease throughout the world. Since 2020, the dermatology community has worked collaboratively in the fight against COVID-19, establishing a worldwide registry for cutaneous manifestations of SARS-CoV-2 and pursuing research that has allowed colleagues in the house of medicine to better understand this landmark disease. Through the study and promotion of global health, dermatologists have an important role in the house of medicine.


Phylogenetic relationships within the Laridae (Charadriiformes: Aves) inferred from mitochondrial markers.
Gulls (Aves: Laridae) constitute a recent and cosmopolite family of well-studied seabirds for which a robust phylogeny is needed to perform comparative and biogeographical analyses. The present study, the first molecular phylogeny of all Larids species (N=53), is based on a combined segment of mtDNA (partial cytochrome b and control region). We discuss our phylogenetic tree in the light of previous suggestions based on morphological, behavioral, and plumage characters. Although the phylogeny is not fully resolved, it highlights several robust species groups and confirms or identifies for the first time some sister relationships that had never been suggested before. The Dolphin Gull (Leucophaeus scoresbii) for instance, is identified as the sister species of the Grey Gull (Larus modestus) and the Ross's Gull (Rhodostethia rosea) forms a monophyletic group with the Little Gull (Larus minutus). Our results clearly demonstrate that the genus Larus as currently defined is not monophyletic, since current taxonomy of gulls is based on the use of convergent phenotypic characters. We propose a new systematic arrangement that better reflects their evolutionary history.


[Effect of neurotropic agents on the healing of experimental mucosal erosions and on the noradrenaline content in the stomach wall].
In immobilized rats with hemorrhagic erosions of gastric mucosa induced by 8-hour electric stimulation, the neurotropic agents were injected intraperitoneally over three days after stimulation was discontinued. Phenamine and melipramine were conductive to healing of the mucous membrane erosions and produced no effect on the recovery of noradrenaline level in the intestinal wall. Clonidin and reserpin inhibited erosion healing and noradrenalline level recovery, whereas eterofen and atropin elicited no effect on the test parameters.


Renal function after abdominal aortic aneurysm repair in patients with baseline chronic renal insufficiency: open vs. endovascular repair.
The aim of this study is to analyze renal function impairment (RFI) after abdominal aortic aneurysm (AAA) repair in patients with preoperative chronic kidney disease (CKD). Retrospective cohort study of patients with CKD undergoing elective AAA repair between 2008-2015, dividing the sample into two groups: open repair (OR) and endovascular repair (EVAR). The primary outcome was RFI defined by the RIFLE scale, studying Risk (1.5-fold increase in Cr or GFR decline >25% compared to baseline) and kidney injury (doubling of Cr or GFR decline >50%). Seventy-five patients (OR=29, EVAR=46). Baseline characteristics for OR and EVAR were similar except for age (70.4 vs. 77.2 years; P<0.001), coronary artery disease (31% vs. 56.5%; P=0.04), neck length (12.3 vs. 22.7 mm; P=0.001) and baseline GFR (40.6 vs. 36.9 mL/min; P=0.03). There were no inter-group differences in postoperative RFI: Risk of RFI 13.8% OR vs. 13% EVAR and kidney Injury 6.9% vs. 0% (P=0.19). There were also no differences in RFI at one year. Comparing GFR and Cr after surgery and at 12 months to baseline values, the OR group presented a significant postoperative decline in GFR compared to EVAR group (-3.8% vs. 11.1%; P=0.03), which had recovered at one-year follow-up (16.6% vs. 9.5%; P=0.43), while EVAR group presented with a tendency toward increased Cr during follow-up (-9.2% vs. 2.2%; P=0.08). Multivariate analysis did not identify independent RFI prognostic factors. Both techniques can be used safely in patients with CKD and baseline CKD is not a limiting factor for either technique. RFI is rare and transient in both groups.


Phagocytosis of alpha-tocopheryl nicotinate by the reticuloendothelial system: a microautoradiographic study.
The cellular distribution of labelled alpha-tocopheryl nicotinate after intravenous administration to normal rats was examined by light microscopic autoradiography. The compound was found to have accumulated in cells of the reticuloendothelial system.


Molecular characterization and expression analyses of ST8Sia II and IV in piglets during postnatal development: lack of correlation between transcription and posttranslational levels.
The two mammalian α2,8-polysialyltransferases (polyST's), ST8Sia II (STX) and ST8Sia IV (PST), catalyze synthesis of the α2-8-linked polysialic acid (polySia) glycans on neural cell adhesion molecules (NCAMs). The objective of this study was to clone the coding sequence of the piglet ST8Sia II and determine the mRNA expression levels of ST8Sia II, ST8Sia IV, NCAM and neuropilin-2 (NRP-2), also a carrier protein of polySia, during postnatal development. The amino acid sequence deduced from the coding sequence of ST8Sia II was compared with seven other mammalian species. Piglet ST8Sia II was highly conserved and shared 67.8% sequence identity with ST8Sia IV. Genes coding for ST8Sia II and IV were differentially expressed and distinctly different in neural and non-neural tissues at postnatal days 3 and 38. Unexpectedly, the cellular levels of mRNA coding for ST8Sia II and IV showed no correlation with the posttranslational level of polySia glycans in different tissues. In contrast, mRNA abundance coding for NCAM and neuropilin-2 correlated with expression of ST8Sia II and IV. These findings show that the cellular abundance of ST8Sia II and IV in postnatal piglets is regulated at the level of translation/posttranslation, and not at the level of transcription, a finding that has not been previously reported. These studies further highlight differences in the molecular mechanisms controlling polysialylation in adult rodents and neonatal piglets.


Tissue poromechanical deformation effects on steam pop likelihood in 3-D radiofrequency cardiac ablation.
Radiofrequency Cardiac Ablation (RFCA) is a common procedure that heats cardiac tissue to destroy abnormal signal pathways to eliminate arrhythmias. The complex multiphysics phenomena during this procedure need to be better understood to improve both procedure and device design. A deformable poromechanical model of cardiac tissue was developed that coupled joule heating from the electrode, heat transfer, and blood flow from normal perfusion and thermally driven natural convection, which mimics the real tissue structure more closely and provides more realistic results compared to previous models. The expansion of tissue from temperature rise reduces blood velocity, leading to increased tissue temperature, thus affecting steam pop occurrence. Detailed temperature velocity, and thermal expansion of the tissue provided a comprehensive picture of the process. Poromechanical expansion of the tissue from temperature rise reduces blood velocity, increasing tissue temperature. Tissue properties influence temperatures, with lower porosity increasing the temperatures slightly, due to lower velocities. Deeper electrode insertion raises temperature due to increased current flow. The results demonstrate that a 5% increase in porosity leads to a considerable 10% increase in maximum tissue temperature. These insights should greatly help in avoiding undesirable heating effects that can lead to steam pop and in designing improved electrodes.


Neurophysiologic markers of abnormal brain activity in schizophrenia.
Cortical electrophysiologic event-related potentials are multidimensional measures of information processing that are well-suited for efficiently parsing automatic and controlled components of cognition that span the range of deficits evidenced in schizophrenia patients. These information processes are key cognitive measures that are recognized as informative and valid targets for understanding the neurobiology of schizophrenia. These measures may be used in concert with the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) neurocognitive measures in the development of novel treatments for schizophrenia and related neuropsychiatric disorders. The employment of novel event-related potential paradigms designed to carefully characterize the early spectrum of perceptual and cognitive information processing allows investigators to identify the neurophysiologic basis of cognitive dysfunction in schizophrenia and to examine the associated clinical and functional impairments.


Intranuclear particles in keratoacanthoma: possible association with malignant degeneration.
Electron microscopic investigation of 12 patients with keratoacanthoma is reported. Intranuclear virus-like particles, as described by Zelickson and Lynch, were seen in 3 cases; 2 of these subsequently underwent malignant degeneration. These findings suggest that it is particularly important to exclude the possibility of malignant change in those tumours when intranuclear particles are found.


Capsaicin-sensitive structures as potential target sites for neurotensin and bradykinin in guinea pig atria.
We tested the influence of capsaicin (CAP) desensitization on the positive chronotropic and inotropic effects of neurotensin (NT), bradykinin (BK), calcitonin gene-related peptide (CGRP) and noradrenaline (NA) in guinea pig isolated atria. The positive chronotropic and inotropic effects of NT and BK were completely inhibited, whereas those elicited by CGRP and NA were either slightly reduced (CGRP) or unaffected (NA), in CAP-desensitized compared to control atria. Cross-desensitization studies using CAP, NT and BK showed that the positive chronotropic and inotropic effects of CAP are slightly affected, whereas those evoked by BK are markedly reduced in NT-desensitized atria. On the other hand, the positive chronotropic and inotropic effects of CAP and NT were similar in BK-desensitized and control atria. The results were interpreted as an indication that NT, BK and CAP produce their excitatory effects in guinea pig atria by interacting with a common population of CAP-sensitive sensory nerve fibers (presumably substance P (SP)- and CGRP-containing nerve fibers). The absence of cross-desensitization between NT or BK and CAP, or between NT and BK, suggests that the activation and desensitization of atrial, CAP-sensitive sensory nerve fibers by the latter agents involve different receptors and/or mechanisms.


A retrospective study of Yiqi-Huoxue Decoction on blood pressure in patients with acute ischemic stroke.
This retrospective study investigated the effect of Yiqi-Huoxue Decoction (YQHXD) on blood pressure (BP) in patients with acute ischemic stroke (AIS).A total of 72 patients with BP following AIS who received routine treatment were included in this retrospective study. Of those, 36 patients received YQHXD and were assigned to a treatment group. The other 36 patients were allocated to a control group. All patients were treated for a total of 4 months. The outcomes were assessed by systolic blood pressure (SBP), diastolic blood pressure (DBP), National Institutes of Health Stroke Scale (NIHSS) score and Barthel index scale (BIS). All outcomes were measured after 4-month treatment.After treatment, all subjects in the treatment group showed greater improvements in SBP (P < .05), DBP (P < .05), NIHSS (P < .05) score, and BIS (P < .05) than those of patients in the control group. In addition, the safety profile is similar in both groups.The findings of this study demonstrated that YQHXD may benefit on BP in patients with AIS. Future studies should focus on warranting the current results.


Cutaneous tuberculosis of the foot clinically mimicking mycetoma: A case report.
In a resource-limited setting such as Sudan, where diagnostic and surveillance capacities are limited and several dermal diseases with similar clinical presentation are endemic, further precautious must taking into account. Cutaneous tuberculosis (CTB) is a rare infection caused by Mycobacterium tuberculosis. Atypical clinical presentations of CTB may resemble other skin neglected diseases. For definitive diagnosis, we require a holistic diagnostic approach including clinical examination and deployment of laboratory investigations including microbial culture, histopathological, and molecular examinations of the proper samples per test. In this communication, we report a case of CTB that was initially misidentified clinically as mycetoma.


On the evolutionary coexistence of parasite strains.
Classical models of parasite competition show that coexistence is impossible if different strains give complete cross-immunity. However, parasite coexistence is possible if some of the model assumptions are changed. For instance, coexistence is impossible if density-dependence operates only in hosts' fertility, but surprisingly becomes possible if hosts' mortality is density-dependent. Parasite strains can also coexist if a host already infected with one strain may become infected by another strain (superinfection). I examine here if these reasons for coexistence carry over to evolutionary timescales: in other words, suppose that potentially a continuum of parasite strains may arise by mutations; will evolution arrive at a halt? in that case, will only one or several strains persist? The paradigm and methods of adaptive dynamics are used in this study. It is found, under reasonably general assumptions, that a unique evolutionarily stable state for virulence, alpha(*), exist for both models. However, the pattern of the invasibility plots depends on the shape of the trade-off (between virulence and transmissibility, or superinfection rates) functions, and on the host demography. In many cases, the state alpha(*) is evolutionarily stable only with respect to small mutations, not to larger ones; hence, evolutionary dynamics will bring virulence to alpha(*) only if mutations are sufficiently small; for larger mutations, evolutionary dynamics are more complex and still mainly unresolved.


HSP90 inhibitors strengthen extracellular ATP-stimulated synthesis of interleukin-6 in osteoblasts: Amplification of p38 MAP kinase.
Heat shock protein 90 (HSP90) is expressed ubiquitously in a variety of cell types including osteoblasts. HSP90 acts as a key driver of proteostasis under pathophysiological conditions. Here, we investigated the involvement of HSP90 in extracellular ATP-stimulated interleukin (IL)-6 synthesis and HSP90 downstream signalling in osteoblast-like MC3T3-E1 cells. In osteoblasts, extracellular ATP stimulates the synthesis of IL-6, a bone-remodelling agent. Geldanamycin, 17-allylamino-17-demethoxy-geldanamycin (17-AAG) and onalespib, three different HSP90 inhibitors, amplified the ATP-stimulated IL-6 release. Geldanamycin increased IL-6 mRNA expression elicited by ATP. ATP enhanced the triiodothyronine-induced osteocalcin release, but HSP90 inhibitors suppressed the release. Extracellular ATP induced the phosphorylation of p44/p42 mitogen-activated protein kinase (MAPK), p38 MAPK, c-Jun N-terminal kinase (JNK), p70 S6 kinase, Akt, and myosin phosphatase-targeting subunit (MYPT), a Rho-kinase substrate. SB203580, an inhibitor of p38 MAPK, suppressed ATP-stimulated IL-6 release. Inhibitors of MEK1/2 (PD98059), JNK (SP600125), upstream kinase of p70 S6 kinase (rapamycin) and Akt (deguelin), all increased IL-6 release. Y27632, a Rho-kinase inhibitor, failed to affect the IL-6 release stimulated by ATP. Geldanamycin and 17-AAG both amplified ATP-induced p38 MAPK phosphorylation, although geldanamycin inhibited the phosphorylation of Akt induced by ATP. In addition, SB203580 significantly reduced the amplification by geldanamycin of the IL-6 release. Taken together, our results strongly suggest that HSP90 inhibitors up-regulate extracellular ATP-stimulated IL-6 synthesis via amplification of p38 MAPK activation in osteoblasts. SIGNIFICANCE OF THE STUDY: Heat shock protein 90 (HSP90) acts as a key driver of proteostasis under pathophysiological conditions in a variety of cell types. We have previously shown that HSP90 is expressed at high levels in osteoblast-like MC3T3-E1 cells, even in their quiescent state, consistent with HSP90 performing an important physiological function in osteoblasts. In the present study, we investigated whether HSP90 is implicated in extracellular ATP-induced interleukin (IL)-6 synthesis in osteoblast-like MC3T3-E1 cells. Our results strongly suggest that HSP90 inhibitors up-regulate extracellular ATP-stimulated IL-6 synthesis via amplification of p38 mitogen-activated protein kinase activation in osteoblasts.


An alternative synthesis of 4,4-dimethyl-5 alpha-cholesta-8,14,24-trien-3 beta-ol, an intermediate in sterol biosynthesis and a reported activator of meiosis and of nuclear orphan receptor LXR alpha.
4,4-dimethyl-5 alpha-cholesta-8,14,24-trien-3 beta-ol, a sterol of current biological interest, has been synthesized in six steps from 3 beta-acetoxy-4,4-dimethyl-5 alpha-cholest-8(14)-en-15-one.


Real-world treatment patterns and clinical outcomes in patients with AML in Japan who were ineligible for first-line intensive chemotherapy.
Acute myeloid leukemia (AML) predominantly affects elderly adults, and its prognosis worsens with age. Treatment options for patients in Japan ineligible for intensive chemotherapy include cytarabine/aclarubicin ± granulocyte colony-stimulating factor (CA ± G), azacitidine (AZA), low-dose cytarabine (LDAC), targeted therapy, and best supportive care (BSC). The country's aging population and the evolving treatment landscape are contributing to a need to understand treatment pathways and associated outcomes. This retrospective chart review evaluated outcomes in patients across Japan with primary/secondary AML who were ineligible for intensive chemotherapy and began first-line treatment or BSC between 01/01/2015 and 12/31/2018. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and healthcare resource utilization (HRU). Of 199 patients (58% > 75 years), 121 received systemic therapy (38 CA ± G, 37 AZA, 7 LDAC, 39 other) and 78 received BSC. Median OS was 5.4, 9.2, 2.2, 3.8, and 2.2 months for CA ± G, AZA, LDAC, other systemic therapy, and BSC, respectively; median PFS was 3.4, 7.7, 1.6, 2.3, and 2.1 months, respectively. HRU rates were uniformly high, with > 80% patients hospitalized in each cohort. The poor clinical outcomes and high HRU among Japanese AML patients who are ineligible for intensive chemotherapy highlight an unmet need for novel therapies.


Comparative study of the binding of acylureidopenicillins and carbenicillin to human serum proteins.
The binding of the acylureidopenicillins azlocillin and mezlocillin to serum proteins was investigated by means of equilibrium dialysis and ultracentrifugation. The penicillin concentrations were determined by the agar diffusion test and by circular dichroism. The degree of binding is dependent on the penicillin concentration. At a mean penicillin concentration of 20 microgram/ml 39% of azlocillin is bound by serum proteins and 35% of mezlocillin. The acylureidopenicillins are bound to about the same degree by the two proteins albumin and gamma globulin, which occur in different concentrations in serum. The binding affinity delta F degree for the interaction between azlocillin and mezlocillin to human albumin is equal to -15,389 J/mol. The corresponding values for the binding of ampicillin and carbenicillin are -17,340 and -16,800 J/mol. Albumin has one binding site of a high affinity and two binding sites of a low affinity for the acylureidopenicillins. Measurements of partition coefficients of the penicillins for isobutanol and aqueous solution show that the interaction between acylureidopenicillins and serum is mainly hydrophobic in nature. This can be deduced from the fact that for example in the presence of sisomicin azlocillin is not displaced from its albumin binding site, in contrast to carbenicillin. The reason for this difference in behaviour lies in the fact that carbenicillin, like sisomicin, is bound to the serum proteins mainly by ionic bonds. In the case of azlocillin, however, hydrophobic bounds predominate which are not influenced by the ionic bonds of sisomicin.


Disruption of erythrocytes distinguishes fixed cells/tissues from viable cells/tissues following microwave coagulation therapy.
Microwave coagulation therapy (MCT) has recently been applied to treat hepatic tumors. However, the histological changes in the liver following MCT have not been fully elucidated. A type of cell death known as microwave fixation has been reported in areas adjacent to the microwave irradiator electrodes, and these areas are without acid phosphatase (AcP) activity. Diagnosis of microwave-fixed tissue by hematoxylin and eosin (HE) staining is very difficult because morphology is well maintained for months. In an effort to clarify the histological changes and the mechanisms of microwave fixation, we performed HE staining, enzyme histochemistry for AcP, and electron microscopy in both rat and human liver samples after MCT. Although the microwave-fixed tissues maintained their structure on HE staining, membranes of microwave-fixed cells were seriously damaged and there were no apparent organelle structures in these cells on electron microscopy. Erythrocytes were also damaged in these tissues on both light and electron microscopy. The cause of microwave fixation is thought to be injury of the membrane, which is similar to coagulative necrosis. In conclusion, microwave fixation can be considered a type of coagulative necrosis without enzyme digestion. Disruption of erythrocytes on HE staining is an interesting and important diagnostic clue in distinguishing nonviable fixed tissues from viable tissues following MCT.


Diagnosis and treatment of patients with antiphospholipid syndrome: a mixed-method evaluation of care in The Netherlands.
The aims were to gain insight into the care provided to patients with APS in The Netherlands and to identify areas for improvement from the perspective of both patients and medical specialists. APS care was evaluated using qualitative and quantitative methods. Perspectives on APS care were explored using semi-structured interviews with medical specialists, patient focus groups and a cross-sectional, online patient survey. In order to assess current practice, medical records were reviewed retrospectively to collect data on clinical and laboratory manifestations and pharmacological treatment in six Dutch hospitals. Fourteen medical specialists were interviewed, 14 patients participated in the focus groups and 79 patients completed the survey. Medical records of 237 patients were reviewed. Medical record review showed that only one-third of patients were diagnosed with APS within 3 months after entering specialist care. The diagnostic approach and management varied between centres and specialists. Almost 10% of all patients and 7% of triple-positive patients with thrombotic APS were not receiving any anticoagulant treatment at the time of medical record review. Correspondingly, poor recognition and fragmentation of care were reported as the main problems by medical specialists. Additionally, patients reported the lack of accessible, reliable patient education, psychosocial support and trust in physicians as important points for improvement. Delayed diagnosis, variability in management strategies and fragmentation of care were important limitations of APS care identified in this study. A remarkable 10% of patients did not receive any anticoagulant treatment.


Malignant tumors of the head and neck in children: a twenty-year review.
This 20-year (1965-1985) retrospective review identified 241 children under the age of 19 years who presented with a malignancy of the head and neck. Hodgkin's disease and other malignant lymphomas predominated, accounting for 59% of the total number of cases. Soft tissue sarcomas, specifically rhabdomyosarcoma, were the next most common lesions (17.5%). Thyroid carcinomas (10%), neuroblastomas (5%), nasopharyngeal carcinomas (5%), salivary gland malignancies (2.5%), and malignant teratomas (1%) accounted for the remaining cases. The neck was the primary site of presentation, followed by the naso-oropharynx, orbit, face and scalp, salivary glands, and aural region, in descending order of frequency. Advances in the diagnosis, staging and treatment of children with malignant tumors of the head and neck have occurred since the last comprehensive survey of such lesions was published in 1973. Otolaryngologists must be aware of these advances in order to remain active members of a multi-discipline team responsible for the care of these children.


Usefulness of ultrasound and fine needle aspiration cytology of major salivary gland lesions.
To assess the clinical value of ultrasound (US) and fine needle aspiration (FNA) of salivary gland lesions prior to surgery, for preoperative decision-making and long-term follow-up/outcome. We retrospectively analyzed the medical charts of 98 consecutive patients with major salivary gland lesions who were treated in a single medical from 2008 to 2017. Preoperative US and FNA was performed in all patients. Cytology results were compared with histopathological diagnoses. The correlation between preoperative US findings, cytology and histopathological diagnoses was assessed. Twenty-three specimens were histopathologically malignant, and 75 were diagnosed as benign. Three false-positive results diagnosed as malignant in cytology had a final histology of sialadenitis, pleomorphic adenoma and Warthin's tumor, respectively. In six cases, cytology yielded false-negative results. The overall accuracy of FNA in distinguishing benign from malignant lesions was 91%. Sensitivity was 70% and specificity 93%. There was no significant correlation between US features and final pathology, but larger size had some correlation with malignancy (p = 0.306). No complications were observed during or after performing FNA. FNA from salivary gland lesions is safe and in many cases can help in preoperative decision making or surgical planning. Hence, the results of FNA cytology should have an integral role in clinical decision-making and management of major salivary gland lesions. False-negative results do occur and therefore should be used only as an adjunctive measure.


Plasma homocysteine concentration is increased in preeclampsia and is associated with evidence of endothelial activation.
We tested the hypothesis that the independent risk factor for atherosclerosis of increased plasma homocysteine concentration is associated with the pregnancy syndrome of preeclampsia. We further hypothesized that increased plasma homocysteine concentration during pregnancy may advance endothelial dysfunction in preeclampsia by promoting oxidative stress. Antepartum blood samples were collected >/=6 hours after the last meal from 33 women with normal, uncomplicated pregnancies and from 21 women with preeclampsia. These plasma samples were analyzed for concentrations of total homocysteine; folate; triglycerides; creatinine; a marker of endothelial activation, cellular fibronectin; and a marker of oxidative stress, malondialdehyde. The mean value of total plasma homocysteine in preeclampsia was significantly higher than that observed in normal pregnancy (P <. 04). Similarly, plasma malondialdehyde (P <.001), triglyceride (P <. 001), and cellular fibronectin (P <.006) concentrations were also greater in women with preeclampsia than in control subjects. However, no differences were observed between women with preeclampsia and control subjects in folate (P =.97) or creatinine (P =.28) concentrations. Homocysteine concentration did not correlate with plasma creatinine (P =.61), malondialdehyde (P =.32), or triglyceride (P =.89) concentrations. However, cellular fibronectin concentration correlated positively with homocysteine concentration in both women with preeclampsia and control subjects (r = 0.87, P <. 0001, and r = 0.50, P <.004, respectively), and folate concentrations were weakly but negatively correlated with homocysteine values (P =.03, r = 0.32). Total plasma homocysteine concentration is increased in preeclampsia and is significantly correlated with cellular fibronectin concentration, suggesting that homocysteine plays a role in promoting endothelial dysfunction in preeclampsia. Furthermore, despite the use of pregnancy multivitamins and no indications of overt folate deficiency in this subject population, homocysteine concentration weakly and negatively correlates with plasma folate concentration.


Ambient Air Pollution and Cardiorespiratory Outcomes amongst Adults Residing in Four Informal Settlements in the Western Province of South Africa.
Few studies have investigated the relationship between ambient air pollution and cardiorespiratory outcomes in Africa. A cross-sectional study comprising of 572 adults from four informal settlements in the Western Cape, South Africa was conducted. Participants completed a questionnaire adapted from the European Community Respiratory Health Survey, and the National Health and Nutrition Examination Survey questionnaire. Exposure estimates were previously modelled using Land-Use Regression for Particulate Matter (PM2.5) and Nitrogen Dioxide (NO2) at participants' homes. The median age of the participants was 40.7 years, and 88.5% were female. The median annual NO2 level was 19.7 µg/m3 (interquartile range [IQR: 9.6-23.7]) and the median annual PM2.5 level was 9.7 µg/m3 (IQR: 7.3-12.4). Logistic regression analysis was used to assess associations between outcome variables and air pollutants. An interquartile range increase of 5.12 µg/m3 in PM2.5 was significantly associated with an increased prevalence of self-reported chest-pain, [Odds ratio: 1.38 (95% CI: 1.06-1.80)], adjusting for NO2, and other covariates. The study found preliminary circumstantial evidence of an association between annual ambient PM2.5 exposure and self-reported chest-pain (a crude proxy of angina-related pain), even at levels below the South African National Ambient Air Quality Standards.


Prospective study of jellyfish stings from tropical Australia, including the major box jellyfish Chironex fleckeri.
To determine the immediate and delayed effects of jellyfish stings, and correlate these with microscopic identification of jellyfish nematocysts. Prospective study of patients presenting with jellyfish stings. 40 people presenting with jellyfish stings to the emergency department of a teaching hospital in tropical Australia between 1 August 1999 and 31 July 2000. Clinical diagnosis (sting by Chironex fleckeri, "Darwin carybdeid" or other jellyfish, or "Irukandji" syndrome); clinical severity; delayed hypersensitivity; and sticky-tape sampling and microscopic identification of nematocysts. Patients were aged 2-50 years, with eight aged under 15 years; 23 were male. Presentations were consistent with C. fleckeri sting in 28 cases, Darwin carybdeid sting in five, and Irukandji syndrome in four. Sticky-tape sampling was done in 39 patients and was positive for C. fleckeri nematocysts in 23 and for non-C. fleckeri nematocysts in six, with nematocysts not detected in 10 (including all four with Irukandji syndrome). All microscopically confirmed C. fleckeri stings had typical clinical presentations. None of the stings were life-threatening, and no antivenom was given. Delayed hypersensitivity reactions were seen in 11 of the 19 patients (58%) followed up after stings positive for C. fleckeri nematocysts. Although most jellyfish stings presenting to Royal Darwin Hospital I were caused by C. fleckeri, severe envenomation was rare. There was a strong association between clinical features and sticky-tape identification of nematocysts. Delayed hypersensitivity was common after C. fleckeri stings.


Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy.
Neuropathic pain (NP) is a sustained and nonreversible condition characterized by long-term devastating physical and psychological damage. Therefore, it is urgent to identify an effective treatment for NP. Unfortunately, the precise pathogenesis of NP has not been elucidated. Currently, the microbiota-gut-brain axis has drawn increasing attention, and the emerging role of gut microbiota is investigated in numerous diseases including NP. Gut microbiota is considered as a pivotal regulator in immune, neural, endocrine, and metabolic signaling pathways, which participates in forming a complex network to affect the development of NP directly or indirectly. In this review, we conclude the current understanding of preclinical and clinical findings regarding the role of gut microbiota in NP and provide a novel therapeutic method for pain relief by medication and dietary interventions.


[Relationship between the mosaicism of myocardial damage and the metabolic heterogeneity of myocardiocytes].
Uridine-3H (2 muCi/g of body weight) was injected intraperitoneally to albino mice; this was followed (in one hour) by isopropylnoradrenaline (0.1 mg/g of body weight). The animals were sacrified in 10 minutes. Autoradiographic analysis and polarisation-microscopic study of the myocardial section showed that myokardiocytes with a lower level of the RNA synthesis were to the contracture lesions.


Prevalence of antibody to Hepatitis B core antigen and Hepatitis B virus DNA in HBsAg negative healthy blood donors.
Hepatitis B virus is one of the most important blood born viruses. Although the sensitivity of screening tests has been considerably increased, transmission may still occur due to window period or occult hepatitis B infections (OBIs). This study was aimed at evaluating the prevalence of the anti-HBc and identifying the HBV DNA in HBsAg negative blood donors. The Blood samples from 2031 HBsAg-negative blood donors were divided into three aliquots and tested for anti-HBc, anti-HBs and HBV DNA. Serologic screening including anti-HBc and anti-HBs was performed. As a confirmatory test, all positive results for anti-HBc were retested with another kit. Two positive results were considered for anti-HBc positivity. All HBsAg negative selected donations were tested by PCR assay on pooled specimens (five samples per pool), plasma samples found to be HBsAg negative but anti-HBc positive were selected for a single-unit specimen Real-Time assay. The study population had a mean age of 33.25 ± 10.09 years were mainly composed of males (94.8 %). The seroprevalance rate was 4.9 % for Anti-HBc and 31.9 % for HBsAb. The majority (58.6 %) of Anti-HBc positive cases were regular blood donors with 42-49 years being the largest age group (41.4 %). Neither individual NAT nor pooled NAT test detected any HBV DNA. However, Screening of anti-HBc Ab is proposed as a method to identify previous contact with HBV, but there is controversy in literature data regarding the cost-benefit of exclusion of positive anti-HBc Ab in blood donors. Our data does not suggest HBc-Ab test as a screening tool in the study setting.


Anti-obesity effects of ginsenoside Rh2 are associated with the activation of AMPK signaling pathway in 3T3-L1 adipocyte.
Metabolic disorders such as obesity are major obstacles in improving the average life span. Therefore, a therapeutic approach using natural compounds has been proposed as a novel strategy for preventing metabolic disorders. Ginsenoside Rh2 is one of the ginsenosides that exert anti-diabetes, anti-inflammatory, and anti-cancer effects. However, the anti-obesity effects of Ginsenoside Rh2 remain unclear. Here, we investigated the anti-obesity ability of ginsenoside Rh2 using cell culture systems. Ginsenoside Rh2 effectively inhibited adipocyte differentiation via PPAR-gamma inhibition. Next, to find specific target molecules based on this result, we used cell culture systems to examine whether AMPK activation was involved in the anti-obesity ability of ginsenoside Rh2 since several published papers have indicated that AMPK signaling is involved in the regulation of metabolic disorders. Ginsenoside Rh2 significantly activated AMPK in 3T3-L1 adipocytes. In addition, we also examined the effect of AMPK on lipolysis molecules such as CPT-1 and UCP-2 by using an AMPK inhibitor. Ginsenoside Rh2 effectively induced CPT-1 and UCP-2 and this induction was abolished by AMPK inhibitor treatment. Moreover, we observed that ROS is an important upstream signal for AMPK activation during ginsenoside Rh2 treatment. Taken together, these results indicate that ginsenoside Rh2 is the most effective candidate for preventing metabolic disorders such as obesity and that it acts via the AMPK signaling pathway. Thus, AMPK signaling might contribute toward improving human health.


Monte Carlo simulation and delayed geochemical hazard revealed the contamination and risk of arsenic in natural water sources.
Due to its ubiquity and carcinogenicity, the geochemical behavior and health risks of arsenic (As) have been a research focus worldwide. A comprehensive investigation was conducted on the contamination and ecological and health risks of As in the Zijiang River (ZR)-a natural water source. The concentration ranges of As were separately 1.36-6.23 μg/L, 11.42-74.53 mg/kg, and 1.26-130.68 μg/L in surface waters (dissolved), sediments, and pore waters. The concentrations of As in the midstream pore waters and sediments were relatively high, which was related to mining, dam interception, and sediment resuspension. The Monte Carlo simulation results showed that the occurrence probability of As contamination and static risk in sediments was low, however, in the midstream, the secondary risk caused by the release of As should be given more consideration. In the sediments, the transformation paths and the dynamic risk of As were explored based on the delayed geochemical hazard model, showing that there was a probability of a potential burst of 26.47% - 55.88% in the sediments of the ZR. Although at the detected surface waters, the total risk of the noncarcinogenicity and carcinogenicity of As were low, overall adults have lower health risks than children, and As exposure in children should be of concern. This study complements the further understanding of the geochemical behavior of arsenic, which can be extended to other toxic metal(loid)s.


Depression, anxiety, quality of life and coping in women with infertility: A cross-sectional study from India.
The purpose of the present study was to assess the prevalence of depression and anxiety in women with infertility, elucidate the psycho-social factors affecting infertile women, identify the commonly employed coping strategies, and evaluate their self-esteem and quality of life. A total of 150 women with infertility, from a tertiary care hospital, participated in this study. Cross-sectional assessment was performed by using the Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, Rosenberg Self-Esteem Scale, WHO-Quality of life-BREF, and Brief-COPE Inventory. Overall, 58% (87/150) of women reported depression on HDRS, 24% (36/150) reported anxiety on HAM-A, and 24% (36/150) had both depression and anxiety on HDRS and HAM-A. Comparative analysis of women reporting depression and anxiety indicated that they were subjected to significant discrimination, received lower social acceptance, had financial problems, higher depression and anxiety, poorer quality of life, and employed maladaptive coping. Living in a joint family, and using maladaptive coping were significant risk factors for anxiety and depression. Conversely, the family's ability to provide support, share problems, and assist with decision-making, along with receiving support from their spouses, were chief protective factors. Women with infertility experience depression, anxiety, poor quality of life, and employ maladaptive coping. Supportive relationships with one's family and spouse are chief protective factors.


Presynaptic CaMKIIα modulates dopamine D3 receptor activation in striatonigral terminals of the rat brain in a Ca²⁺ dependent manner.
CaMKIIα is expressed at high density in the nucleus accumbens where it binds to postsynaptic D3 receptors inhibiting their effects. In striatonigral projections, activation of presynaptic D3 receptors potentiates D1 receptor-induced stimulation of cAMP production and GABA release. In this study we examined whether the presynaptic effects of D3 receptor stimulation in the substantia nigra reticulata (SNr) are modulated by Ca²⁺ activation of CaMKIIα. In SNr synaptosomes two procedures that increase cytoplasmic Ca²⁺, ionomycin and K⁺-depolarization, blocked the additional stimulation of cAMP accumulation produced by coactivating D3 and D1 dopamine receptors. The selective CaMKIIα inhibitor KN-62 reversed the blockade produced by ionomycin and K⁺-depolarization. Incubation in either Ca²-free solutions or with the selective Ca²⁺ blocker nifedipine, also reversed the blocking effects of K⁺-depolarization. Immunoblot studies showed that K⁺-depolarization increased CaMKIIα phosphorylation in a KN-62 sensitive manner and promoted CaMKIIα binding to D3 receptors. In K⁺-depolarized tissues, D3 receptors potentiated D1 receptor-induced stimulation of [³H]GABA release only when CaMKIIα was blocked with KN-62. In the presence of this inhibitor, the selective D3 agonist PD 128,907 reduced the ED₅₀ for the D1 agonist SKF 38393 from 56 to 4 nM. KN-62 also enhanced the effects of dopamine on depolarization induced [³H]GABA release. KN-62 changed ED₅₀ for dopamine from 584 to 56 nM. KN-62 did not affect D1 and D4 receptor responses. These experiments show that in striatonigral projections, CaMKIIα inhibits the action of D3 receptors in a Ca²⁺ dependent manner blocking their modulatory effects on GABA release. These findings suggest a mechanism through which the frequency of action potential discharge in presynaptic terminals regulates dopamine effects.


Pain on a surgical ward: a survey of the duration and intensity of pain and the effectiveness of medication.
The effectiveness of analgesic medication for post-surgical pain was surveyed in a surgical ward of a large general hospital. Since earlier studies have shown that pain generally decreases rapidly and is negligible by the fourth day after surgery, the patients in the survey were assigned to 2 groups: those given analgesics during the first 4 days after surgery, and those given analgesics for pain after the fourth day. The results show that the patients with pain that persists beyond day 4 comprise a substantial proportion of the patients in a surgery ward (31%), are older, tend to use more words to describe their pain, and are helped less by their prescribed analgesic medications. This group is prescribed lower doses of analgesics and receives them more frequently; however, this prescription strategy appears to be ineffective since 26% of these patients report increased pain after medication compared to only 2% in the group that received analgesics during the first 4 days.


Giant polypeptides of skeletal muscle titin: sedimentation equilibrium in guanidine hydrochloride.
Titin has been purified from rabbit skeletal myofibrils in guanidine hydrochloride by gel filtration on Sephacryl S-1000. The sedimentation coefficients of denatured titin in 6 M guanidine hydrochloride are highly concentration dependent and follow the equation: 1/S = 0.241 + 0.302 A280. Equilibrium sedimentation studies indicate that the average molecular weight of titin polypeptides is 2.4 to 2.6 X 10(6).


[Phospholipids of pulmonary surfactants and lung elasticity].
We discuss the various preparations of substitute pulmonary surfactant that have been proposed for the treatment of Respiratory Distress Syndrome in premature infants. We than submit some experimental results demonstrating that a preparation of phospholipids in an organic solvent can simulate the behavior of the naturally occurring pulmonary surfactant as a monolayer at an air-water interface.


Serum and lymph-node collagenase in sarcoidosis. Comparison with angiotensin-converting enzyme.
Serum collagenase was significantly elevated in stage II, but not stage I sarcoidosis, in contrast to elevation of serum angiotensin-converting enzyme in stages I and II. Neither serum collagenase nor angiotensin-converting enzyme was elevated in active tuberculosis. Elevated serum collagenase and angiotensin-converting enzyme levels were decreased with steroid therapy. Serum collagenase and angiotensin-converting enzyme were significantly correlated but did not vary identically. Collagenase was not elevated in lymph nodes in sarcoidosis, in contrast to marked elevation of angiotensin-converting enzyme. The results suggest that serum angiotensin-converting enzyme is a more sensitive index of sarcoidosis activity than serum collagenase, which may have an ancillary role in assessment of the disease.


Genotoxicity of HNE.
Since previous investigations on the genotoxicity of 4-hydroxynonenal (HNE) were carried out with prokaryotic systems or eukaryotic cell lines which may not adequately reflect the response of cells in vivo due to differences in the metabolism, the genotoxic potential of HNE was further evaluated in primary cells (hepatocytes) and cell clones of cerebral endothelial cells expressing specific functions, i.e. blood-brain barrier (BBB) and capillary formation associated phenotypes. Treatment of hepatocytes with HNE induced statistically significant levels of SCE at concentrations >/=0.1 microM, micronuclei at concentrations >/=1 microM and chromosomal aberrations at a concentration of 10 microM. Treatment of cloned cerebral microvascular endothelial cells induced significantly elevated levels of chromosomal aberrations at concentrations >/=1 microM and micronuclei at concentrations >/=10 microM in both cEC phenotypes, compared to the controls. Additionally, cytotoxicity was observed at a concentration of 50 microM HNE and was significantly higher in type II cells. These results indicate that cells expressing differentiated functions representative for the in vivo situation react more sensitive to HNE than cell lines, and may reflect the sensitivity of the target cells. The different response with respect to the endpoints of genotoxicity tested most probably depends on the different metabolizing capacities and thus the action of different metabolites of HNE.