Treatment of relapsed Hodgkin's disease using a weekly chemotherapy of short duration: results of a pilot study in 20 patients.
Twenty patients with relapsed Hodgkin's disease have been treated with a weekly regimen of chemotherapy (VAPEC-B) comprising Adriamycin 35 mg/m2 i.v. weeks 1, 3, 5, 7, 9, 11; cyclophosphamide 350 mg/m2 i.v. weeks 1, 5, 9; etoposide 100 mg/m2 p.o. daily for 5 days, weeks 3, 7, 11; vincristine 1.4 mg/m2 i.v. weeks 2, 4, 6, 8, 10; bleomycin 10 mg/m2 i.v. weeks 2, 6, 10 and prednisolone 50 mg p.o. daily weeks 1-5, 25 mg p.o. daily weeks 6-11. All had previously received an Adriamycin containing combination and in nine cases this was for relapse following MVPP. In all but one case relapse occurred less than one year after the completion of previous treatment and in 14 cases, disease recurred within 24 weeks. Thirteen patients had extra-nodal involvement. Following six weeks of treatment 14 patients had responded (6 CR; 4 CR, uncertain; 4 PR), four had stable disease, one had progressed and one had died of sepsis. Fourteen patients proceeded to high dose cyclophosphamide and BCNU with autologous bone marrow rescue and seven of these are progression free between 4 and 156 weeks later. High dose therapy was not possible in five patients, three of whom achieved CR. Of these, two (one with bulky nodal disease and skin infiltration; one with extensive bone marrow involvement) are alive and relapse free without further treatment at 95 and 114 weeks. Overall, the regimen was well tolerated but haematological toxicity was moderate or severe in ten patients and four were admitted to hospital for treatment of suspected or confirmed septicaemia.(ABSTRACT TRUNCATED AT 250 WORDS)


[A prospective randomized controlled study on the repair of skin and soft tissue defect in functional areas of children with full-thickness skin grafts from different sites of abdomen].
Objective: To compare and analyze the effect of repairing small skin and soft tissue defect wounds in functional areas of children with full-thickness skin grafts from different sites of abdomen. Methods: A prospective randomized controlled study was conducted. From January 2019 to June 2020, 60 female children with small skin and soft tissue defects in functional areas requiring full-thickness skin grafting, who met the inclusion criteria, were admitted to the First Affiliated Hospital of Air Force Medical University. According to the random number table, the children were divided into two groups, with 28 cases left in lateral abdomen group aged 5 (3, 8) years and 29 cases in lower abdomen group aged 5 (3, 7) years after the exclusion of several dropped-out children in follow-up. In lower abdomen group, 20 (12, 26) cm2 wounds of children were repaired with (24±10) cm2 full-thickness skin graft from transverse skin lines in the inferior abdomen area, while in lateral abdomen group, 23 (16, 32) cm2 wounds of children were repaired with (24±9) cm2 full-thickness skin graft from below the umbilical plane to above the groin in the lateral abdomen area. All the children were treated with continuous intradermal suture at the donor site incision and received continuous negative pressure treatment of -10.64 to -6.65 kPa in the donor and recipient areas after operation. The donor site was treated with a medical skin tension-reducing closure device since post-surgery day (PSD) 7. The use of medical skin tension-reducing closure device at the donor site, postoperative complications and suture removal time of the donor area were recorded, and the incidence of complications was calculated. On PSD 7, a self-designed efficacy satisfaction questionnaire was used to investigate the parents' satisfaction with the curative effect of their children. In post-surgery month (PSM) 1 and 6, Vancouver scar scale (VSS) was used to evaluate the scar at the donor site, and the VSS score difference between the two time points was calculated; the scar width at the donor site was measured with a ruler, and the scar width difference between the two time points was calculated. Data were statistically analyzed with independent sample t test or Cochran & Cox approximate t test, Mann-Whitney U test, and Fisher's exact probability test. Results: The proportion of children in lateral abdomen group who used the medical skin tension-reducing closure device in the donor area for equal to or more than 4 weeks after surgery was significantly higher than that in lower abdomen group (P<0.05). On PSD 7, there was one case of partial incision dehiscence in the donor area, one case of peripheral skin redness and swelling in the donor area, and one case of fat liquefaction in the donor area in lateral abdomen group, and one case of partial incision dehiscence in the donor area in lower abdomen group. The incidence of postoperative complications at the donor site of children in lower abdomen group was significantly lower than that in lateral abdomen group (P<0.05). Compared with that in lateral abdomen group, the suture removal time at the donor site of children after surgery in lower abdomen group was significantly shorter (t'=17.23, P<0.01). On PSD 7, the satisfaction score of parents with the curative effect of their children in lower abdomen group was significantly higher than that in lateral abdomen group (t'=20.14, P<0.01). In PSM 1 and 6, the VSS scores of scar at the donor site of children in lower abdomen group were 2.7±0.9 and 2.8±1.0, respectively, which were significantly lower than 7.1±2.2 and 9.1±2.7 in lateral abdomen group (with t values of 10.00 and 11.15, respectively, P<0.01). In PSM 6, the VSS score of scar at the donor site of children in lateral abdomen group was significantly higher than that in PSM 1 (t=3.10, P<0.01), while the VSS score of scar at the donor site of children in lower abdomen group was not significantly higher than that in PSM 1 (P>0.05). The VSS score difference of scar at the donor site of children in lateral abdomen group was significantly greater than that in lower abdomen group (Z=-8.12, P<0.01). In PSM 1 and 6, the scar widths at the donor site of children in lower abdomen group were 2.0 (1.0, 2.0) and 2.0 (2.0, 3.0) mm, respectively, which were significantly narrower than 6.0 (4.0, 10.0) and 8.5 (5.0, 12.0) mm in lateral abdomen group (with Z values of -13.41 and -14.70, respectively, P<0.01). In PSM 6, the scar width at the donor site of children in lateral abdomen group was significantly wider than that in PSM 1 (Z=-2.79, P<0.01), while the scar width at the donor site of children in lower abdomen group was not significantly wider than that in PSM 1 (P>0.05). The difference of scar width at the donor site of children in lateral abdomen group was significantly greater than that in lower abdomen group (Z=-14.93, P<0.01). Conclusions: The use of full-thickness skin grafts from the lower abdomen to repair small skin and soft tissue defect wounds in functional areas of children, especially girls, is effective, simple and easy to operate, and conforms to the principle of aesthetic repair. Compared with transplantation with full-thickness skin graft from the lateral abdomen, lower abdominal full-thickness skin grafting has a low incidence of donor site complications and no obvious scar hyperplasia, which is worthy of clinical promotion.


Propagation factors of cosine-Gaussian-correlated Schell-model beams in non-Kolmogorov turbulence.
Based on the extended Huygens-Fresnel principle and second-order moments of the Wigner distribution function (WDF), we have studied the relative root-mean-square (rms) angular width and the propagation factor of cosine-Gaussian-correlated Schell-model (CGSM) beams propagating in non-Kolmogorov turbulence. It has been found that the CGSM beam has advantage over the Gaussian Schell-model (GSM) beam for reducing the turbulence-induced degradation, and this advantage will be more obvious for the beams with larger parameter n and spatial coherence δ or under the condition of stronger fluctuation of turbulence. The CGSM beam with larger parameter n or smaller spatial coherence δ will be less affected by the turbulence. In addition, the effects of the slope-parameter α, inner and outer scale and the refractive-index structure constant of the non-Kolmogorov's power spectrum on the propagation factor are also analyzed in detailed.


Present and future studies on lipogenesis in animals and human subjects.
Lipogenesis occurs in all vertebrate species and has a critical role in energy balance, providing a means whereby excess energy can be stored as a fat. The metabolic pathways involved and their tissue distribution in different species, including man, are well known. The responses of lipogenesis to diet and to physiological and pathological states have been the subject of many studies. At a molecular level the major rate-controlling enzymes have been identified and their acute, and to a lesser extent chronic, control by hormones have been investigated extensively. However, there is no reason to suppose that all factors regarding lipogenesis have been identified (e.g. the recent discovery of acylation-stimulating protein). Little is known about the movement of newly-synthesized triacylglycerols in cells, either for secretion or storage. The production of leptin and tumour necrosis factor alpha by adipocytes provides a novel means of feedback control of triacylglycerol production, leptin by decreasing appetite and tumour necrosis factor alpha by inducing insulin resistance. The synthesis of these peptides appears to vary with the amount of triacylglycerol in adipocytes, but the molecular basis of this process is unknown. Elucidation of the signalling systems involved in the acute and chronic regulation of lipogenesis is also important, both with respect to some homeorhetic adaptations and also in some pathological conditions (e.g. non-insulin-dependent diabetes). Finally, molecular biology is revealing unexpected complexities, such as multiple promoters and different isoforms of enzymes (e.g. acetyl-CoA carboxylase; EC 188.8.131.52) exhibiting tissue specificity. Molecular biology, through transgenesis, also offers novel and powerful means of manipulating lipogenesis.


Signet-ring cells associated with pseudomembranous colitis.
After being treated for pneumonia with antibiotics, an 82-year-old man with a history of colonic carcinoma developed pseudomembranous colitis with toxic megacolon. In addition to the classic features of pseudomembranous colitis, the colon displayed signet-ring cells confined to the surface epithelium and crypts. A misdiagnosis of recurrent carcinoma was avoided after a review of the history and the endoscopic findings and by noting the location of the signet-ring cells.


Veiled communication: is uncovering necessary for psychiatric assessment?
Facial expressions are significant to decipher information during a dialogue and more so in a clinical consultation. Veils (Niqab) worn by Muslim women may pose a clinical dilemma for the psychiatric assessment especially if clinicians are not aware of their religious significance. To investigate whether clinical judgment is affected if full facial expressions are not accessible, we conducted an email survey of psychiatrists and psychologists across the world who frequently work in these situations. Of 25 colleagues contacted 16 responded and 11 of them agreed for their comments to be included in the study. Nine out of 11 believed clinical assessment may be compromised, although respondents were aware of cultural sensitivity around the issue. Two out of 11 however, felt fully able to assess the mental state of a veiled woman. Some professionals reported that they feel unable to assess or treat if the request to take the veil off is declined. This small survey demonstrates the diverse opinions on whether unveiling is necessary for psychiatric assessment. Further qualitative examination of this area is needed to develop wider consensus and guidance to mental health care professionals who may be dealing with these groups.


Inhibition of bilirubin metabolism induces moderate hyperbilirubinemia and attenuates ANG II-dependent hypertension in mice.
Population studies indicate that moderate hyperbilirubinemia is associated with reduced incidence of cardiovascular diseases, including hypertension. Despite this correlative evidence, no studies have directly tested the hypothesis that moderate increases in plasma bilirubin levels can attenuate the development of hypertension. This hypothesis was tested by treating mice with Indinavir, a drug that competes with bilirubin for metabolism by UDP-glucuronosyltransferase 1A1 (UGT1A1). Treatment of mice with Indinavir (500 mg x kg(-1) x day(-1), gavage) resulted in a twofold increase in plasma unconjugated bilirubin levels. Next, we determined the effect of Indinavir-induced changes in plasma bilirubin on the development of ANG II-dependent hypertension. Moderate hyperbilirubinemia was induced 3 days before the implantation of an osmotic minipump that delivered ANG II at a rate of 1 microg x kg(-1) x min(-1). ANG II infusion increased mean arterial pressure (MAP) by 20 mmHg in control mice but by only 6 mmHg in mice treated with Indinavir (n = 6). Similar to Indinavir treatment, direct infusion of bilirubin (37.2 mg x kg(-1) x day(-1) i.v.) resulted in a twofold increase in plasma bilirubin levels and also attenuated the development of ANG II-dependent hypertension. Moderate hyperbilirubinemia resulted in an increase in plasma nitrate/nitrite levels, which averaged 36 +/- 2 vs. 50 +/- 7 microM in ANG II vehicle vs. Indinavir-treated mice (n = 5). Moderate hyperbilirubinemia resulted in attenuation of vascular oxidative stress as determined by dihydroethidium staining of aortic segments. These results indicate that moderate hyperbilirubinemia prevents ANG II-dependent hypertension by a mechanism that may involve decreases in vascular oxidative stress.


Confocal microscopy assessment of filling material remaining on root canal walls after retreatment.
The percentage of Endofill remaining on canal walls after retreatment with different techniques was evaluated using confocal microscopy and qualitative analysis of the interface between the filling material/dentine. Sixty-four root canals of incisors were prepared with ProTaper, filled with gutta-percha and Endofill mixed with 0.1% rhodamine B. The roots were thermocycled and distributed into groups according to the method of evaluation: GI - direct viewing (DV) and GII - operating microscope (OM) and according to the removal technique: A) ProTaper retreatment (PR), B) PR/xylol, C) ultrasound and D) ultrasound/xylol. The root canals were then refilled with gutta-percha and AH Plus with 0.1% fluorescein and sectioned at 2, 4 and 6 mm from the apex. The percentage of remaining Endofill was analysed by confocal microscopy. Additionally, 16 roots were prepared with a ProTaper F5 instrument and were filled with Endofill + 0.1% rhodamine B/gutta-percha (negative control group) (n = 8), and the positive control group (n = 8) were filled with AH Plus with 0.1% fluorescein/gutta-percha. Three-way anova demonstrated differences in the method of evaluation, removal techniques and their interaction (P < 0.05). OM (26.15 ± 12.16%) had a smaller percentage of remaining sealer than DV (32.77 ± 14.47%). The Tukey's test revealed that ultrasound/xylol (15.77 ± 7.15%) led to lower percentages of remaining sealer, significantly different from the PR group (35.25 ± 13.63%), PR/xylol (33.03 ± 11.64%) and ultrasound (33.79 ± 11.71%), which were similar (P > 0.05). Qualitative analysis detected that ultrasound had lower remaining Endofill than PR, particularly when combined with xylol. Operating microscope resulted in lower residual sealer, regardless of the removal technique. None of the protocols was associated with complete removal of the filling material; however, the use of ultrasound/xylol under an OM provided better results.


Deep Tissue Microscopic Imaging of the Kidney with a Gradient-Index Lens System.
Intravital microscopy using two-photon excitation is proven to be a valuable tool for studying the kidney and associated disease processes. However, routine performance of intravital kidney imaging is limited by the fact that fluorescence signal is attenuated by the tissue and at certain tissue depth lost its strength completely. For most of the animal tissues, this finite imaging depth is limited to a few hundred microns. Currently it is not possible to non-invasively image the kidney beyond the superficial tissue layers of the cortex. This has imposed significant limitations on the animal models one can use for imaging since structure such the glomerulus is typically located below the superficial layer of the cortex that can not be imaged using a conventional fluorescence microscope. Here we report the use of a needle-like lens system based on gradient-index (GRIN) microlenses capable of transferring high quality fluorescence images of the tissue through a regular microscope objective for deep tissue imaging of the kidney. By combining this GRIN lens system with a Zeiss LSM 510 NLO microscope, we are able to extend the imaging depth for kidney tissues far beyond the few hundred microns limit. This GRIN lens imaging system provides an alternative microendoscopic imaging tool that will enhance current intravital kidney imaging techniques for studying structural and functional properties of local tissues at locations below the superficial layers of the kidney.


Peritoneal interleukin-8 in acute appendicitis.
Interleukin-8 (IL-8) is a chemoattractant that is highly selective for neutrophils. This study was designed to investigate the presence of IL-8 in peritoneal fluid of patients with acute appendicitis. The clinical circumstances underlying the secretion of IL-8 by mesothelium and its mechanism of activation have not been defined. In an in vitro model for bacterial peritonitis the role of bacteria in activating human mesothelial cells to secrete IL-8 was studied. Cultured human mesothelium was incubated with various species of pathogenic bacteria, isolated from peritoneal exudate fluids of patients with appendicitis. The amount of IL-8 secreted by the cultured mesothelial cells was determined in an IL-8 ELISA, as IL-8 was present in the original peritoneal fluid of these patients. Peritoneal fluids from patients with a perforated appendix were found to contain a significantly higher concentration of IL-8 compared to peritoneal fluids from patients with nonperforating appendicitis (121.6 (57.8) ng/ml versus 0.2 (0.07) ng/ml, respectively; mean (SEM), P < or = 0.01). Species of Bacteroïdes and Fusobacterium necrophorum induced IL-8 secretion from cultured mesothelial monolayers to levels comparable to those found in peritoneal fluids in vivo. Heat-killed bacteria and bacterial supernatant were also able to stimulate mesothelium to secrete IL-8. The results suggest that in the early phase of bacterial peritonitis the influx of PMN is regulated by bacteria-induced IL-8 secretion by the mesothelium lining the peritoneal cavity.


[Pre-eclampsia].
Pre-eclampsia or toxaemia of pregnancy is a multi-organ disorder in the second half of pregnancy. Approximately 1-3% of all pregnancies in the Netherlands are complicated by this condition. The disease is characterised by vascular damage resulting in hypertension and proteinuria with high morbidity for both mother and child. The underlying cause is a poorly developed placenta. To date the only real treatment comprises medicinal protection against complications and the disorder can be cured only through termination of pregnancy. Complications range from severe hypertension to maternal mortality due to cerebral haemorrhage. Long-term consequences can be severe for both mother and child. For instance, the risk of cardiovascular disease in mothers in later life is significantly increased. Many risk factors have been identified, including diabetes, BMI and an age of above 40. The association between periodontal disease and pre-eclampsia emphasises the importance of good oral hygiene in the periconceptional period.


[Serum metalloproteinase-3 levels in assessing efficacy of Etanercept in patients with ankylosing spondylitis].
To investigate the value of metalloproteinase-3 (MMP-3) levels in assessing efficacy of etanercept treatment in patients with ankylosing spondylitis (AS). The serum and synovial fluid levels of MMP-3 were measured by enzyme linked immunosorbent assay (ELISA) in 48 patients with AS in week 0, 6 and 12; and also measured in 30 serum samples and 10 synovial fluid samples from healthy controls. The serum levels of MMP-3 in AS patients were significantly higher than those in controls. In AS patients, the MMP-3 levels in synovial fluid were significantly higher than those in serum levels. The serum MMP-3 levels in AS patients with peripheral arthritis were higher than those with exclusively axial involvement; while C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) did not differ between these 2 groups of AS. At week 6 and week 12 of etanercept treatment, the serum MMP-3 levels were significantly decreased (p<0.01) with the declining trend of ESR, CRP, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) (all p<0.01). Before the etanercept treatment (week 0), serum levels of MMP-3 were correlated with ESR, CRP, BASDAI and BASFI (p<0.05). ESR was also correlated with CRP and BASFI, but not with BASDAI (r=0.361, P=0.071). At weeks 12, serum MMP-3 levels were still correlated with ESR, CRP and BASDAI (P<0.05), but not with BASFI (P=0.339); ESR was correlated with CRP, but not with BASDAI and BASFI. There was a significant correlation between BASDAI and BASFI (r=0.818,P=0.001). Serum MMP-3 levels are closely related to disease activity and may serve as an useful indicator for efficacy of etanercept treatment in AS patients.


Stakeholder controls and conflicts in research funding and publication.
Academics are required by their university employers both to raise research funding and to publish research findings, but conditions imposed by research funders may conflict with the requirements of research publishers. These conflicts create risks, with potentially severe consequences, that differ between research fields and funders, and must be navigated by individual academics. I propose that universities report cases of conflict, including causes and resolutions, to national registries accessible to all research organisations. These could serve both as a warning to grant applicants, and a deterrent to future interference by funders.


Development of environmental thresholds for nitrogen and phosphorus in streams.
Inputs of nutrients (P and N) to freshwaters can cause excessive aquatic plant growth, depletion of oxygen, and deleterious changes in diversity of aquatic fauna. As part of a "National Agri-Environmental Standards Initiative," the Government of Canada committed to developing environmental thresholds for nutrients to protect ecological condition of agricultural streams. Analysis of data from >200 long-term monitoring stations across Canada and detailed ecological study at ~70 sites showed that agricultural land cover was associated with increased nutrient concentrations in streams and this, in turn, was associated with increased sestonic and benthic algal abundance, loss of sensitive benthic macroinvertebrate taxa, and an increase in benthic diatom taxa indicative of eutrophication. Chemical thresholds for N and P were defined by applying five approaches, employing either a predetermined percentile to a water chemistry data set or a relationship between water chemistry and land cover, to identify boundaries between minimally disturbed and impaired conditions. Comparison of these chemical thresholds with biological thresholds (derived from stressor-response relationships) produced an approach for rationalizing these two types of thresholds and deriving nutrient criteria. The resulting criteria were 0.01 to 0.03 mg L(-1) total P and 0.87-1.2 mg L(-1) total N for the Atlantic Maritime, 0.02 mg L(-1) total P and 0.21 mg L(-1) total N for the Montane Cordillera, ~0.03 mg L(-1) total P and ~1.1 mg L(-1) total N for the Mixedwood Plains, and ~0.10 mg L(-1) total P and 0.39-0.98 mg L(-1) total N for the interior prairies of Canada. Adoption of these criteria should result in greater likelihood of good ecological condition with respect to benthic algal abundance, diatom composition, and macroinvertebrate composition.


Role of therapeutic exercises in neurogenic thoracic outlet syndrome.
Neurogenic Thoracic Outlet Syndrome (TOS) is a set of signs and symptoms existing due to compression of brachial plexus in the cervical area. We performed the study to highlight the role of therapeutic exercises on patients with neurogenic thoracic Outlet Syndrome. This quasi-experimental study was carried out at Armed Forces Institute of Rehabilitation Medicine (AFIRM), Rawalpindi. Fifty consecutive patients of neurogenic TOS of both genders and all ages were selected. Patients were diagnosed clinically and the diagnosis was confirmed by electrodiagnosis. These patients were asked to follow a therapeutic exercises program for 6 months. Outcome measures included Visual Analogue Scale (VAS) and Ulnar Nerve Conduction Velocity across neck. Results were compared by applying relevant tests of significance on follow up visits at 3 and 6 months. Mean age was 39.1 +/- 7.79 years. Thirty seven (74%) cases were females and thirteen (26%) were males. On each visit, statistical analysis showed significant improvement with therapeutic exercises. After 6 months of conservative treatment, 17 (34%) of patients showed full recovery, 14 (28%) had marked improvement, 16 (32%) had partial improvement while 3 (6%) patients reported with persistent severe symptoms. Current study shows that a trial of therapeutic exercises provides relief of symptoms of Neurogenic Thoracic Outlet Syndrome in majority of patients.


Knowledge and Management of Halitosis in France and Lebanon: A Questionnaire-Based Study.
Halitosis is a growing issue and its management is highly challenging. The aim of this study was to evaluate the knowledge and treatment strategies used by French (FD) and Lebanese (LD) dentists. A self-administered structured questionnaire was sent to FD and LD comprising questions about professional characteristics, management, and treatment of halitosis, patients' referral, and halitosis-related knowledge. A multivariate analysis was conducted to determine differences between FD and LD and to identify parameters that could influence dentists' management of halitosis. The questionnaire was filled out by 156 FD and 257 LD. Among them, 78.8% of FD and 68.9% of LD were confronted with halitosis management, while only a few routinely asked their patients about halitosis (16% FD, 13.2% LD). Regarding anamnesis, oral hygiene habits were more investigated by FD than LD (p < 0.05). The overall treatment satisfaction was low with 39.7% of FD and 28.4% of LD considering their treatment effective. Regarding halitosis-related knowledge, extra-oral causes were overestimated in both populations. FD (83.4%) and LD (65.8%) considered their education regarding halitosis as insufficient. This study highlights the need of professional education in both countries, targeting proper diagnosis and treatment strategies of halitosis.


[French neurosurgery in the Bosnia-Herzegovina conflict].
Seven French neurosurgical missions, from June 1994 to December 1996, were sent successively to Bosnia-Herzegovina with the help of a non-governmental organisation Médecins du Monde. The aim of this article is to present the working conditions, make an overall evaluation of the missions and then to draw lessons and discuss the limits. The initial aim of these neurosurgical missions was: i) to provide human and logistic support to the Bosniac teams in the field; ii) to exchange knowledge and help in the training of local young neurosurgeons; iii) to be present as witnesses. The towns of Tuzla and Zenica in Eastern and Central Bosnia respectively were chosen as the missions bases. One hundred five neurosurgical operations were carried out in precarious conditions, particularly concerning anesthesia. The largest number of the operations (52%) concerned standard neurosurgical pathologies, without any direct link to the war but which had been put off or made difficult due to the war. Cranioplasties and peripheric nerve injuries were the main lesions directly related to the war situation which the French missions had to deal with. Actually, war neurosurgical pathologies were very often dealt with in emergency by Bosniac teams in the field hospitals near the front. Previously existing neurosurgical environment, in particular with access to a scanner is an absolute necessity to carry out a good quality neurosurgical mission. Precarious anesthesia and operating conditions require the surgical team to adapt to local conditions, but are not a contra-indication to such missions. Although help in the field can prove useful on occasions, training the resident teams is important. This can be done locally, but additional training in a neurosurgically developed country is fundamental. Missions such as these require relatively major funding (about 150 000 French francs for each of our missions) and suitable infrastructures. Prior to undertaking this type of mission, a neurosurgeon must evaluate local human and equipment needs.


Influence of extracorporeal shock-wave application on normal bone in an animal model in vivo. Scintigraphy, MRI and histopathology.
There is little information about the effects of extracorporeal shock-wave application (ESWA) on normal bone physiology. We have therefore investigated the effects of ESWA on intact distal rabbit femora in vivo. The animals received 1500 shock-wave pulses each of different energy flux densities (EFD) on either the left or right femur or remained untreated. The effects were studied by bone scintigraphy, MRI and histopathological examination. Ten days after ESWA (0.5 mJ/mm2 and 0.9 mJ/mm2 EFD), local blood flow and bone metabolism were decreased, but were increased 28 days after ESWA (0.9 mJ/mm2). One day after ESWA with 0.9 mJ/mm2 EFD but not with 0.5 mJ/mm2, there were signs of soft-tissue oedema, epiperiosteal fluid and bone-marrow oedema on MRI. In addition, deposits of haemosiderin were found epiperiosteally and within the marrow cavity ten days after ESWA. We conclude that ESWA with both 0.5 mJ/mm2 and 0.9 mJ/mm2 EFD affected the normal bone physiology in the distal rabbit femur. Considerable damaging side-effects were observed with 0.9 mJ/mm2 EFD on periosteal soft tissue and tissue within the bone-marrow cavity.


Effects of age and physical activity status on redistribution of joint work during walking.
During walking older adults rely less on ankle and more on hip work than young adults. Disproportionate declines in plantarflexor strength may be a mechanism underlying this proximal work redistribution. We tested the hypothesis that proximal redistribution is more apparent in older compared to young adults and in sedentary compared to active individuals over multiple walking speeds. We recruited 18 young (18-35 yrs) and 17 older (65-80 yrs) physically active and sedentary adults. Participants completed five trials at four walking speeds as marker positions and ground reaction forces were collected. Sagittal plane net joint moments were computed using inverse dynamics. Instantaneous joint powers for the ankle, knee, and hip were computed as products of net joint moments and joint angular velocities. Positive joint work was computed by integrating hip, knee, and ankle joint powers over time in early, mid, and late stance, respectively. Relative joint work was expressed as a percentage of total work. Isokinetic strength of lower limb flexor and extensor muscles was measured. Older adults had lower relative ankle (p=0.005) and higher relative hip (p=0.007) work than young adults for multiple speeds. Non-significant trends (p<0.10) indicating sedentary participants had lower relative ankle (p=0.068) and higher relative hip work (p=0.087) than active adults were observed. Age-related differences in plantarflexor strength were not disproportionate compared to strength differences in knee and hip musculature. Age influenced proximal work redistribution over multiple walking speeds. Physical activity status showed a similar trend for proximal work redistribution, but failed to reach statistical significance.


Efficacy of anti-leishmania therapy in visceral leishmaniasis among HIV infected patients: a systematic review with indirect comparison.
We conducted a systematic literature review with indirect comparison of studies evaluating therapeutic efficacy and toxicity associated to visceral leishmaniasis (VL) therapy among HIV infected individuals. The outcomes of interest were clinical and parasitological cure, mortality, and adverse events. PRISMA guidelines for systematic reviews and Cochrane manual were followed. Sources were MEDLINE, LILACS, EMBASE, Web of Knowledge databases and manual search of references from evaluated studies. We included all studies reporting outcomes after VL treatment, regardless of their design. Study quality was evaluated systematically by using the Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Comprehensive Meta-Analysis software v.2.2.048 was used to perform one-group meta-analysis of study arms with the same drug to estimate global rates of success and adverse events with each drug. These estimates were used, when possible, to indirectly compare treatment options, adjusted for CD4 count. Direct comparison was pooled when available. Seventeen studies reporting five treatment regimens and outcome of 920 VL episodes occurring in HIV infected individuals were included. The main outstanding difference in outcome among the treatment regimens was observed in mortality rate: it was around 3 times higher with high-dose antimony use (18.4%, CI 95% 13.3-25%), indirectly compared to lipid formulations of amphotericin B treatment (6.1%, CI 95% 3.9-9.4%). It was observed, also by indirect comparison, higher rates of clinical improvement in study arms using amphotericin B than in study arms using pentavalent antimonial therapy (Sb(v)). The parasitological cure, an outcome that presented some degree of risk of selection and verification bias, had rates that varied widely within the same treatment arm, with high heterogeneity, hampering any formal comparison among drugs. One direct comparison of amphotericin and antimoniate was possible combining results of two studies and confirming the superiority of amphotericin. Available evidence suggests that amphotericin is superior to antimony treatment. Death rate using antimoniate high dose is unacceptably high. Randomized controlled trials are necessary to compare different formulations and doses of amphotericin, alternative therapies and drug combinations.


Dynamic transition in deposition with a poisoning species.
In deposition with a poisoning species, we show that the transition to a blocked or pinned phase may be viewed as an absorbing transition in the directed percolation (DP) class. We consider a ballisticlike deposition model with an active and an inactive species that represents the basic features of the process and exhibits a transition from a growing phase to a blocked phase, with the deposition rate as the order parameter. In the growing phase, the interface width shows a crossover from the critical W approximately t behavior to Kardar-Parisi-Zhang (KPZ) scaling, which involves DP and KPZ exponents in the saturation regime. In the pinned phase, the maximum heights and widths scale as H(s) approximately W(s) approximately (p-p(c))(-nu). The robustness of the DP class suggests investigations in real systems.


HPLC of folinic acid diastereoisomers and 5-methyltetrahydrofolate in plasma.
We present a rapid, sensitive, and automated HPLC method with direct resolution of l-folinic acid (l-FA), d-folinic acid (d-FA), and 5-methyltetrahydrofolate (5MTHF) from plasma samples. Plasma (500 microL) is first extracted on solid phase (RP-18 cartridge). The dI-FA peak is collected on-line from a reversed-phase column (RP-8, 119 x 2 mm, 4 microns: HPLC 1) and then automatically loaded onto a chiral stationary phase (human serum albumin, 150 x 4.6 mm, 7 microns: HPLC 2). The same mobile phase flows in both systems (0.2 mol/L Na2HPO4:1-propanol, 98:2, pH 6.2). HPLC 1 allows quantification of 5MTHF by absorption at 313 nm; HPLC 2, the quantification of l-FA and d-FA by electrochemical detection in the oxidation mode (total run time 18 min). Recoveries are > 80%. CVs for intra- and interassay reproducibilities are < 5% and 15%, respectively. Linearity of the response (0.1-1 mumol/L and 1-50 mumol/L, r = 0.99, P < 0.01) is satisfactory. The sensitivity limit is 50 nmol/L for 5MTHF and 20 nmol/L for l-FA and d-FA. This assay is substantially improved over existing methods regarding feasibility and is being used in pharmacokinetic investigations in cancer patients.


Genetic Diseases of Vitamin D Metabolizing Enzymes.
Vitamin D metabolism involves 3 highly specific cytochrome P450 (CYP) enzymes (25-hydroxylase, 1α-hydroxylase, and 24-hydroxylase) involved in the activation of vitamin D3 to the hormonal form, 1,25-(OH)2D3, and the inactivation of 1,25-(OH)2D3 to biliary excretory products. Mutations of the activating enzymes CYP2R1 and CYP27B1 cause lack of normal 1,25-(OH)2D3 synthesis and result in rickets whereas mutations of the inactivating enzyme CYP24A1 cause build-up of excess 1,25-(OH)2D3 and result in hypercalcemia, nephrolithiasis, and nephrocalcinosis. This article reviews the literature for 3 clinical conditions. Symptoms, diagnosis, treatment, and management of vitamin D-dependent rickets and idiopathic infantile hypercalcemia are discussed.


Oesophageal cancer and alcoholic spirits in central Africa.
A geographical pathology survey of a large area in central Africa is described and a contrast is recognized between neighbouring areas with apparently many and apparently few cases of oesophageal cancer. This distribution is compared first with other known areas of high and low incidence in sub-Saharan Africa and then with the drinking of indigenous types of distilled spirits. A significant order of spatial correlation is shown between the geographical pattern of the disease and the drinking of sugar-based alcoholic spirit in central Africa. Samples of spirits from eastern Zambia, central Kenya, and the Transkei, although prepared in apparently dissimilar utensils, were all shown to be contaminated in varying degree with zinc. Nitrosamine-like compounds in native spirits were also reported in all these areas. The need for a geographical survey of indigenous drinking habits in Africa is illustrated. Since legislation against distilling is ineffective, a simple means of excluding carcinogenic compounds from illicit spirits should be ascertained and widely promulgated at village level.


Bilateral endogenous bacterial panophthalmitis.
We present a case of meningitis with bilateral endogenous bacterial panophthalmitis in a previously healthy individual. The management of this ocular condition is unclear, and the prognosis is poor. The patient was admitted to the Clinic of Eye Diseases after a 9-day treatment with systemic antibiotics with a complete systemic recovery but impaired vision of both eyes. Functional vision was restored in the better eye with intravitreal vancomycin and pars plana vitrectomy. Nevertheless, after the removal of silicone oil, phthisis bulbi began to develop. Better outcomes could be expected if bacteremic patients were examined routinely by an ophthalmologist and, in case of endogenous bacterial endophthalmitis, treated with intravitreal antibiotics.


AANA Journal Course: update for nurse anesthetists-brain death: terminology, clinical criteria, and diagnostic testing.
Developmental strides in biomedical technology and the growth and availability of intensive care units have paralleled the development of organ transplantation programs. The establishment of these programs required the development of a new definition, criteria, and test of death to facilitate the procurement of suitable organs. The historical definition of death, in instances of organ transplantation, is no longer compatible as cardiopulmonary support can be readily applied to individuals without spontaneous circulation and respiration. This AANA Journal course will examine the definitions of death and the evolution of the term "brain death." The essential clinical criteria and confirmatory diagnostic testing for the determination of adult "whole-brain death" will be reviewed.


Serinolamides and Lyngbyabellins from an Okeania sp. Cyanobacterium Collected from the Red Sea.
NMR- and MS-guided fractionation of an extract of an Okeania sp. marine cyanobacterium, collected from the Red Sea, led to the isolation of four new metabolites, including serinolamides C (1) and D (2) and lyngbyabellins O (3) and P (4), together with the three known substances lyngbyabellins F (5) and G (6) and dolastatin 16 (7). The planar structures of the new compounds were determined using NMR and MS analyses. The absolute configurations of 1 and 2 were determined by Marfey's analysis of their hydrolysates. The absolute configuration of 3 was ascertained by chiral-phase chromatography of degradation products, while that of 4 was determined by comparison to 3 and 5. The cytotoxic and antifouling activities of these compounds were evaluated using MCF7 breast cancer cells and Amphibalanus amphitrite larvae, respectively. Compounds 3, 4, and 7 exhibited strong antifouling activity, and 3 and 7 were not cytotoxic. A structure-activity relationship was observed for the cytotoxicity of the lyngbyabellins with the presence of a side chain (4 is more active than 3) leading to greater activity. For the antifouling activity, the acyclic form without a side chain (3) was the most active.


Endobronchial ultrasound for mediastinal staging in lung cancer patients.
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has changed the way mediastinal staging is performed in lung cancer patients. EBUS-TBNA is probably the most important non-invasive procedure for mediastinal staging and the currently preferred approach in many reference cancer centres worldwide. EBUS-TBNA is a less invasive technique than mediastinoscopy with low morbidity and no mortality and can be performed in an outpatient setting with excellent results. This study describes the technical aspects of EBUS-TBNA and our personal experience with the procedure.


Do carbamates cause polyneuropathy?
Carbamates are reversible inhibitors of acetylcholinesterase, and some also inhibit neuropathy target esterase (NTE), the target in organophosphate-induced delayed polyneuropathy. However, based on mechanistic considerations, these carbamates were thought to be unable to initiate polyneuropathy. Consequently, clinical reports of polyneuropathy associated with carbamate exposures have been disregarded. We discuss three cases of polyneuropathy that occurred after severe poisoning by methylcarbamates. In addition, high repeated doses of phenyl N-methyl N-benzylcarbamate caused nearly 100% NTE inhibition and polyneuropathy in the hen model. These data suggest the need to reconsider the long-standing tenet that carbamates cannot cause polyneuropathy. Alternatively, a preexisting subclinical neuropathy in these individuals may have been amplified by carbamates, as observed in animal models. We suggest that individuals with underlying neuropathy (e.g., diabetics) who are poisoned by carbamates should be followed closely. In addition, procedures for the current risk assessment of carbamate pesticides may need to be reconsidered.


Orthostatic hypertension in children and adolescents with postural tachycardia syndrome.
We described a heterogenous group of children disabled by postural tachycardia syndrome (POTS) and evident orthostatic hypertension (OHT). Twenty patients met the diagnostic criteria for POTS + OHT. Their clinical characteristics were compared with those in 76 patients with POTS alone and 20 healthy age-matched controls. Multivariate logistic regression analysis was used to identify independent risk factors for POTS + OHT. Supine systolic blood pressure (SBP) was lower in the POTS + OHT group than in the POTS group (p < 0.05). Compared with the POTS group, the POTS + OHT group showed markedly increased upright SBP, upright heart rate (HR) and HR changes (p < 0.05). Headache was more common in the POTS + OHT group than in the POTS group (p < 0.05). Logistic regression analysis revealed that low supine SBP and headache were independent risk factors for OHT in POTS patients. Headache and low supine SBP were the main clinical characteristics of a novel syndrome of POTS associated with OHT.


Hearing loss after general anaesthesia (a case report and review of literature).
Unilateral hearing loss has been reported as an unusual complication in general anaesthesia, and so far no reports on bilateral hearing loss have been published. In this paper we present a case with bilateral sensorineural hearing impairment immediately following a minor abdominal surgical procedure. The literature is reviewed and the mechanisms causing hearing loss during anaesthesia are discussed.


Prof. Il-Hoi Kim: a tribute.
Prof. Il-Hoi Kim was born during the Korean War on 28 February 1952 in Buan, North Jeolla Province (South Korea), near the coast of the Yellow Sea whose tidal flats would become one of his favourite sampling grounds during his scientific career. From an early age he developed an intense interest in natural history in general and marine biology in particular. He obtained his B.Sc. in 1974 at the Department of Biology Education, Gongju National College of Education. Between 1974 and 1976 he was conscripted into the South Korean military during which he progressed to the rank of lieutenant of artillery in the Reserve Officers' Training Corps (ROTC). After his graduation in 1980 at the Department of Zoology, Seoul National University, Il-Hoi Kim moved to the Department of Biology, Gangneung-Wonju National University on the East Sea coast where he was first appointed lecturer (1981) before taking up the position of assistant professor (1983), associate professor (1987) and full professor (1993). In 1985 he had previously completed his Ph.D. dissertation on Korean barnacles at Seoul National University under the supervision of the late Prof. Hoon Soo Kim, a pioneer in marine invertebrate taxonomy and renowned as the father of carcinology in Korea.


Exercise Tolerance Test: a comparison between true positive and false positive test results.
To study the factors which predetermine the coronary artery disease in patients having positive Exercise Tolerance Test (ETT) after comparing the ETT test results and coronary angiographic findings in true positive and false positive groups. This Cross-sectional study was conducted at Punjab Institute of Cardiology, Lahore from January 1, 2004 to December 31, 2004. All patients who had ETT done for chest pain diagnosis were studied. Patients were advised coronary angiography if ETT was positive for exercise induced ischaemia. One hundred and forty eight patients had coronary angiography done after positive ETT. Patients were divided into two groups depending upon the angiographic findings, i.e., true positive and false positive. Both groups were compared with each other. Out of 148 patients, 126 (85.1%) patients had true positive ETT and 22 (14.9%) patients had false positive ETT. The mean age of patients in true positive group was 48.96 +/- 9.08 years and 50.9 +/- 7.85 years in false positive group. One hundred and eighteen (93.7%) male patients and 8 (6.3%) female patients had true positive ETT, whereas 14 (63.6%) males and 8 (36.4%) females had false positive ETT (p < 0.0001). There was no statistically significant difference in the two groups in comparison of age and other conventional risk factors like diabetes mellitus, hypertension, smoking, family history and dyslipidemia. Abnormal resting ECG had a statistically significant diffErence between the groups (p < 0.04), likewise is hypertensive haemodynamic response during ETT (p < 0.003). The symptom limited ETT as compared to no symptoms during ETT also conferred a statistically significant difference between the groups (p < 0.0001). Strongly positive ETT was also associated with true positive ETT (p < 0.002). Amongst the vessels involved the most common was the LAD 113 (89.7%), followed by LCX 80 (63.5%) and the RCA 72 (57.1%). Most of the patients 51 (40.5%) had three vessel disease as compared to SVD 34 (27%). It can be concluded that amongst the patients who have positive ETT, females with abnormal resting ECG, who achieve target heart rate and have a hypertensive haemodynamic response with no symptoms are likely to have a false positive test result. Conversely male patients with normal resting ECG who do not achieve target heart rate, have a normotensive haemodynamic response and a strongly positive, symptom limited ETT are likely to have a true positive treadmill test result.


Obstructive sleep apnea and cardiovascular disease.
Obstructive sleep apnea (OSA) is a sleep-disordered breathing condition, which is increasingly being recognized as having wide-ranging pathophysiological effects on multiple organ systems. Although multiple factors affect the incidence and severity of OSA, male sex and obesity seem to play an influential role. The apnea-ventilation cycle, characterized by abnormalities in gas exchange, exaggerated respiratory effort and frequent arousals, has been shown to have deleterious effects on circulatory hemodynamics, the autonomic milieu, hormonal balance, inflammatory and coagulation cascades, endothelial function, and the redox state, with potential cardiovascular significance. Consequently, OSA is being increasingly implicated in a multitude of cardiovascular diseases (CVD) such as hypertension, congestive heart failure, atrial fibrillation, stroke, coronary artery disease, pulmonary hypertension, and metabolic syndrome. The strength of association for individual CVD is varied, and outcomes of clinical studies are conflicting. In addition, obesity, which is closely linked to both OSA and CVD, makes it harder to ascertain the independent role of OSA on CVD. Although available evidence is inconclusive, there is an increasing recognition of the direct role for OSA in CVD. Similarly, although several studies have demonstrated the cardiovascular benefits of OSA treatment, further studies are needed to confirm this.


Plasmonic imaging of human oral cancer cell communities during programmed cell death by nuclear-targeting silver nanoparticles.
Plasmonic nanoparticles (NPs) have become a useful platform in medicine for potential uses in disease diagnosis and treatment. Recently, it has been reported that plasmonic NPs conjugated to nuclear-targeting peptides cause DNA damage and apoptotic populations in cancer cells. In the present work, we utilized the plasmonic scattering property and the ability of nuclear-targeted silver nanoparticles (NLS/RGD-AgNPs) to induce programmed cell death in order to image in real-time the behavior of human oral squamous carcinoma (HSC-3) cell communities during and after the induction of apoptosis. Plasmonic live-cell imaging revealed that HSC-3 cells behave as nonprofessional phagocytes. The induction of apoptosis in some cells led to attraction of and their subsequent engulfment by neighboring cells. Attraction to apoptotic cells resulted in clustering of the cellular community. Live-cell imaging also revealed that, as the initial concentration of NLS/RGD-AgNPs increases, the rate of self-killing increases and the degree of attraction and clustering decreases. These results are discussed in terms of the proposed mechanism of cells undergoing programmed cell death.


Visceral obesity and hypoadiponectinemia are significant determinants of hepatic dysfunction: An epidemiologic study of 3827 Japanese subjects.
Adiponectin is an anti-inflammatory and insulin-sensitizing adipocytokine, and its serum concentrations are reduced in obesity with visceral fat accumulation. Visceral fat accumulation is an independent determinant of elevated serum liver enzymes. Hypoadiponectinemia plays important roles in the clinical progression of nonalcoholic steatohepatitis. The aim of this study was to evaluate the relation between visceral fat area (VFA), serum adiponectin concentration, and biochemical liver tests, such as aspartate aminotransferase, alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) in normal subjects. The study group comprised 3827 Japanese subjects [mean age+/-SD; 47.6+/-10.7 y: 2854 males (48.4+/-10.7 y), 973 females (45.3+/-10.1 y)], who underwent annual health checkup in 2004. In addition to parameters measured in the annual health checkup, VFA and serum adiponectin concentration were measured by the bioelectrical impedance analysis method and a latex particle-enhanced turbidimetric assay system, respectively. Pearson's correlation analysis showed a significant correlation between VFA and the levels of the above 3 liver enzymes in both sexes, and a significant negative correlation between adiponectin and all biochemical liver tests in men and with ALT and GGT in women. Stepwise multiple regression analysis showed that VFA was a significant determinant of serum liver tests in both sexes. Moreover, serum adiponectin concentration significantly and negatively influenced male ALT and GGT and female GGT. Both visceral obesity and hypoadiponectinemia are significant determinants of subtle and asymptomatic hepatic dysfunction in normal Japanese subjects.


Rhythmic Trafficking of TRPV2 in the Suprachiasmatic Nucleus is Regulated by Prokineticin 2 Signaling.
The mammalian circadian clock is composed of single-cell oscillators. Neurochemical and electrical signaling among these oscillators is important for the normal expression of circadian rhythms. Prokineticin 2 (PK2), encoding a cysteine-rich secreted protein, has been shown to be a critical signaling molecule for the regulation of circadian rhythms. PK2 expression in the suprachiasmatic nucleus (SCN) is highly rhythmic, peaking during the day and being essentially absent during the night. Mice with disrupted PK2 gene or its receptor PKR2 display greatly reduced rhythmicity of broad circadian parameters such as locomotor activity, body temperature and sleep/wake patterns. PK2 has been shown to increase the firing rate of SCN neurons, with unknown molecular mechanisms. Here we report that TRPV2, an ion channel belonging to the family of TRP, is co-expressed with PKR2 in the SCN neurons. Further, TRPV2 protein, but not TRPV2 mRNA, was shown to oscillate in the SCN in a PK2-dependent manner. Functional studies revealed that TRPV2 enhanced signaling of PKR2 in calcium mobilization or ion current conductance, likely via the increased trafficking of TRPV2 to the cell surface. Taken together, these results indicate that TRPV2 is likely part of the downstream signaling of PK2 in the regulation of the circadian rhythms.


Does Excessive Body Weight Change the Shape of the Spine in Children?
Background: Excessive body weight is a lifestyle issue, which is commonly found in children in many countries worldwide, and has enormous medical implications. This study aimed to determine the effect of overweight and obesity on the shape of the spine in children. Materials and Methods: A total of 910 children 10-12 years of age participated in this study. Their height, weight, and fat tissue content were measured. Their BMI was calculated, and their body weight status was categorized. The shape of the spinal curvature was assessed using an ultrasound Zebris Pointer system. The following parameters were used for the assessment: the shape of the thoracic kyphosis and lumbar lordosis, the sagittal trunk inclination, and alignment of the spine in the frontal plane. Results: An overweight or obesity was found in 23.7% of participants. The thoracic kyphosis was similar in children with a normal and an excessive weight. The BMI and body fat correlated statistically significantly with the shape of lumbar lordosis as well as with the tilt of the long axis of the body. The results revealed that overweight or obesity did not have any effect on the lateral bending of the spine. Conclusions: Excessive body weight was found to increase the risk for developing the lumbar hyperlordosis and cause posterior axial tilt. Therefore, overweight and obese children should participate in gymnastic classes that can help correct faulty posture. Special attention should be paid to correct the position of the lower part of the trunk.


Population of resonance and metastable atoms in a cylindrical volume of finite size.
A solution method of the Holstein-Biberman equation in the case of two-dimensional finite-size geometry by means of transformation of the integral operator to a four-dimensional matrix is presented. Using this matrix the array of two-dimensional eigenvalues and eigenfunctions of the radiation transport operator in the case of finite cylinder is determined. The exact two-dimensional characteristics have been compared with approximate functions determined as a combination of corresponding eigenvalues and eigenfunctions for the one-dimensional problems (cylinder of infinite length and slab). The spatiotemporal evolution of excited atom densities for two typical forms of the excitation source in a nonequilibrium plasma has been analyzed. The reasons for the distinct difference in the formation of spatiotemporal distributions of resonance and metastable atoms in the case when the spatial distribution of the excitation source does not coincide with the fundamental mode are discussed. Resonance atoms follow the excitation source while the diffusion effectively takes metastable atoms out from the excitation source. Rearrangement of metastable atoms to the fundamental mode during their decay lasts about one effective diffusion lifetime while the corresponding process for the resonance atoms takes much longer (several effective lifetimes). The differences are caused by the effective suppression of higher diffusion modes compared with radiation modes. The developed solution method treats the radiation transport processes at the same accuracy level as diffusion transport of other plasma components and it is suitable for a self-consistent modeling of nonequilibrium plasmas.


Psychogenic disorders of vision in childhood ("visual conversion reactions"): perspectives from adolescence: a research note.
Fifteen adolescents who had exhibited psychogenic disorders of vision in childhood were compared with a control group of adolescents who had experienced childhood visual dysfunction of organic origin. The principal modes of assessment were clinical interviews, the Parental Bonding Instrument (PBI), and self-report measures concerning specific personality traits. Adolescents who had previously presented with psychogenic disorder were more likely to (1) report having experienced school difficulties and the loss of a significant figure at the time of presentation, (2) rate their mothers as over-involved on the PBI and (3) report adjustment difficulties and obsessional personality traits in adolescence.


Azuki bean (Vigna angularis) extract reduces oxidative stress and stimulates autophagy in the kidneys of streptozotocin-induced early diabetic rats.
Diabetic kidney disease is associated with oxidative stress, inflammation, and autophagy. The aim of this study was to investigate the effect of azuki bean (Vigna angularis) extract (ABE) on oxidative stress and autophagy in the kidneys of diabetic rats. Streptozotocin (STZ)-induced diabetic rats received 0, 10, or 40 mg/kg of ABE orally for 4 weeks, whereas vehicle-injected control rats received distilled water. Level of plasma glutathione and expression of heme oxygenase-1 (HO-1), p47phox (NADPH oxidase subunit), and markers associated with autophagy were examined. The glutathione level in the 40 mg/kg ABE-treated diabetic group (ABE-40 group) was higher than that of the untreated diabetic group (ABE-0 group). The HO-1 and p47phox protein expression levels of the ABE-40 group were lower (47% and 33%, respectively) than those of the ABE-0 group. The level of light chain 3B II (LC3B-II) was higher in the ABE-40 group than in the ABE-0 group. Protein levels of p62/sequestosome 1 (p62) in the ABE-40 group were lower than those in the ABE-0 group. Our results suggest that ABE may attenuate STZ-induced diabetic kidney injury by suppressing oxidative stress and (or) by upregulating autophagy.


Ion-Specific and pH-Dependent Hydration of Mica-Electrolyte Interfaces.
Hydration forces play a crucial role in a wide range of phenomena in physics, chemistry, and biology. Here, we study the hydration of mica surfaces in contact with various alkali chloride solutions over a wide range of concentrations and pH values. Using atomic force microscopy and molecular dynamics simulations, we demonstrate that hydration forces consist of a superposition of a monotonically decaying and an oscillatory part, each with a unique dependence on the specific type of cation. The monotonic hydration force gradually decreases in strength with decreasing bulk hydration energy, leading to a transition from an overall repulsive (Li+, Na+) to an attractive (Rb+, Cs+) force. The oscillatory part, in contrast, displays a binary character, being hardly affected by the presence of strongly hydrated cations (Li+, Na+), but it becomes completely suppressed in the presence of weakly hydrated cations (Rb+, Cs+), in agreement with a less pronounced water structure in simulations. For both aspects, K+ plays an intermediate role, and decreasing pH follows the trend of increasing Rb+ and Cs+ concentrations.


Dosimetric impact of multileaf collimator leaf width according to sophisticated grade of technique in the IMRT and VMAT planning for pituitary adenoma lesion.
We analyzed the difference in the dosimetric effect between 5-mm and 2.5-mm multileaf collimator (MLC) leaf width according to the sophisticated grades of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). Nineteen patients with pituitary adenomas were selected for this study. The treatment plans were performed according to the size of the MLC (5-mm and 2.5-mm MLC), the type of technique (IMRT and VMAT), and the sophisticated grades of each technique (5-field, 9-field, 13-field, 17-field technique in IMRT and 1-arc and 2-arc techniques in VMAT). The downsizing effects of MLC leaf width were analyzed using target volume coverage (TVC), conformity index (CI), dose gradient index (GI), and normal tissue difference 70% isodose line and 50% isodose line. Upon replacing the 5-mm MLC with the 2.5-mm MLC, TVC and CI improved by 1.30% and 1.36%, respectively, in total plans. The TVC and CI improved by 1.68% and 1.67% in IMRT, respectively, and by 0.54% and 0.72% in VMAT, respectively. TVC improved by 2.53%, 1.82%, 1.34%, and 0.94%, and CI also improved by 2.70%, 1.81%, 1.24%, and 0.94%, in 5-field, 9-field, 13-field, and 17-field IMRT, respectively. TVC improved by 0.66% and 0.43%, and CI also improved by 0.93%, and 0.52% in 1-arc and 2-arc VMAT, respectively. Regarding the target coverage, there were dosimetric benefits of a smaller MLC leaf width. However, the downsizing effect of the MLC leaf width decreased with the use of a more precise RT technique and a more sophisticated grade of the same technique.


Comparison of the structural features of ubiquinone reduction sites between glucose dehydrogenase in Escherichia coli and bovine heart mitochondrial complex I.
To characterize the structural features of the ubiquinone reduction site of glucose dehydrogenase (GlcDH) in Escherichia coli, we performed structure/activity studies of a systematic set of synthetic ubiquinone analogues and specific inhibitors (synthetic capsaicins) of this site. Considering the proposed similarity of the quinone binding domain motif between GlcDH and one subunit of mitochondrial complex I [Friedrich, T., Strohdeicher, M., Hofhaus, G., Preis, D., Sahm, H. & Weiss, H. (1990) FEBS Lett. 265, 37-40], we compared the structure/activity profiles of the substrates and inhibitors for GlcDH with those for bovine heart mitochondrial complex i. With respect to GlcDH, replacement of one or both methoxy groups in the 2 and 3 positions of benzoquinone ring by ethoxy group(s) resulted in a drastic decrease in the electron accepting activity. The presence of a 5-methyl group and the conformational property of the 6-alkyl side chain did not significantly contribute to the activity. These results suggested that only half of the benzoquinone ring (the moiety corresponding to the 2 and 3 positions) is recognized by the quinone reduction site in a strict sense. In contrast, quinone analogues with structural modifications at all positions in the benzoquinone ring retained the activity with mitochondrial complex I. This finding indicated that the catalytic site of complex I is spacious enough to accommodate a variety of structurally different quinone derivatives. The correlation of the inhibitory potencies of a series of synthetic capsaicins between the two enzymes was very poor. These findings indicated that the binding environment of ubiquinone in GlcDH is very specific and differs from that in mitochondrial complex I.


Early Recognition and Successful Treatment of Anti-synthetase Syndrome.
Anti-synthetase syndrome is an autoimmune disorder that is characterized by inflammatory myopathy, non-erosive polyarthritis, interstitial lung disease in addition to the presence of anti-aminoacyl t-RNA synthetase antibody. It can have variable presentations posing a major diagnostic challenge. Recognition of this syndrome is crucial for appropriate, timely therapy to prevent morbidity and mortality. We report the case of a 55-year-old male who initially presented to the emergency department (ED) with sudden onset shortness of breath, low-grade fever, dry cough, fatigue, and severe arthralgia. He was diagnosed with community-acquired pneumonia and was discharged with antibiotics. He then presented to his primary care physician (PCP) with worsening symptoms. A computed tomography (CT) scan of the chest showed the presence of patchy bilateral airspace opacities and infiltrates. He had elevated inflammatory markers and anti-nuclear antibodies (ANAs). Pulmonary function test (PFT) showed a restrictive pattern with a reduction in lung volumes. Further workup revealed the presence of anti-Jo-1 antibodies. In addition, a muscle biopsy was obtained which showed inflammatory myopathy. Lung biopsy was consistent with interstitial fibrosis. The diagnosis of the anti-synthetase syndrome was made and the patient was promptly started on high-dose prednisone and cyclophosphamide which was later switched to azathioprine and tacrolimus due to resistance and side effects. The patient's symptoms improved significantly with the current treatment without any other complications. This case highlights the importance of a thorough history and physical exam by PCP. Prompt communication and care coordination between PCP and specialists (rheumatologist and pulmonologist) are essential to expedite diagnostic testing and initiate treatment early in this disorder.


The discrimination of and orienting to speech and non-speech sounds in children with autism.
The present study aimed to find out how different stages of cortical auditory processing (sound encoding, discrimination, and orienting) are affected in children with autism. To this end, auditory event-related potentials (ERP) were studied in 15 children with autism and their controls. Their responses were recorded for pitch, duration, and vowel changes in speech stimuli, and for corresponding changes in the non-speech counterparts of the stimuli, while the children watched silent videos and ignored the stimuli. The responses to sound repetition were diminished in amplitude in the children with autism, reflecting impaired sound encoding. The mismatch negativity (MMN), an ERP indexing sound discrimination, was enhanced in the children with autism as far as pitch changes were concerned. This is consistent with earlier studies reporting auditory hypersensitivity and good pitch-processing abilities, as well as with theories proposing enhanced perception of local stimulus features in individuals with autism. The discrimination of duration changes was impaired in these children, however. Finally, involuntary orienting to sound changes, as reflected by the P3a ERP, was more impaired for speech than non-speech sounds in the children with autism, suggesting deficits particularly in social orienting. This has been proposed to be one of the earliest symptoms to emerge, with pervasive effects on later development.


[Drug-induced aseptic meningitis].
Drug-induced aseptic meningitis is a rare adverse effect of some drugs. We report a patient with four episodes of meningitis caused by ibuprofen. In all episodes the patient had taken ibuprofen for pain, and subsequently developed fever and cerebrovascular symptoms. Drug-induced meningitis cannot be distinguished from meningitis caused by other agents. Diagnosis is therefore based on close association between drug administration and onset of symptoms, as well as negative microbiology tests results, especially if previous episodes of drug-induced meningitis have occurred.


Unusually high efficiency of β-cyclodextrin clathrate preparation by water-free solid-phase guest exchange.
An effective preparation procedure is offered for β-cyclodextrin (bCD) clathrates with volatile guests of moderate hydrophilicity, which otherwise require a finely tuned optimization of the bCD/water/guest ratio. The proposed procedure includes guest exchange in a water-free bCD matrix. As a result, more stable clathrates with a higher inclusion capacity can be prepared than by direct saturation of dried or hydrated bCD. To find an optimal preparation method, the structure-property relationships were studied for four different ways of bCD clathrate formation with guests of varying molecular structure. The study was much simplified by used procedures excluding direct contact of guest and water liquids with bCD. Besides, in clathrate preparation experiments, the thermodynamic activities of water and guest were varied independently, which makes explicit the role of water in this process. Hydration of bCD reduces its inclusion threshold for hydrophobic guests by their activity (relative vapor pressure), giving favorable hydration effect for their inclusion. Besides, water competes with hydrophilic guests for binding sites in bCD at high water activities. Together with bCD dehydration by excess of hydrophilic guests, these observations give a complete thermodynamic picture, which may be fruitful for elaboration of guest encapsulation techniques by cyclodextrins.


Multidisciplinary management of cervical neuroblastoma in infants.
Neuroblastoma is the most common malignancy in infancy, it is a histologically and genetically heterogeneous tumor, the therapy and outcome of which is influenced by age, histological variant and genetic background as well. We present two consecutive infant patients with neuroblastoma of the neck discussing the etiology, the diagnosis and the surgical and oncological treatment of the tumor, which was observed in a relatively rare manifestation in the head-neck region. Our first patient (age: 5.5 months) was MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived) negative, INSS (International Neuroblastoma Staging System) Stage 3 and INRGSS (International Neuroblastoma Risk Group Staging System) Stage 3 because of the contralateral lymph node involvement while the complete gross resection of the primary tumor mass was feasible. The patient is tumor free after three years of follow-up. Our second patient (age: 5 months) was MYCN negative, INSS Stage 2 and INRGSS Stage 1, as both the primary tumor and the ipsilateral lymph nodes were totally removed via a modified radical neck dissection. The patient is tumor free after three years of follow-up. For MYCN negative patients, especially in early age, the prognosis of neuroblastoma is good, surgical resection and chemotherapy together is an adequate treatment protocol (as in our two patients). While MYCN-amplified patients require a combined and aggressive treatment with surgery, chemotherapy, radiotherapy, and immunotherapy to be able to obtain a favorable survival rate according to the literature.


Assessment of two protocols for the human lymphocyte cytokinesis-blocked micronucleus assay.
This study indicated that by adding cytochalasin B (6 micrograms/ml) at 24 h, the lymphocyte culture time for micronucleus (MN) assay could be shortened to 64 h. In both unirradiated and ex-vivo irradiated (2 Gy) lymphocytes from three populations, we found that the differences in MN yield obtained by our modified cytokinesis-blocked time frame and that recommended by Fenech and Morley (1985) were insignificant (P = 0.66-0.87). We believe that the shorter assay time may enhance the applicability of MN assay for the rapid assessment of ionizing radiation overexposures.


Involvement of mitochondrial permeability transition pore (mPTP) in cardiac arrhythmias: Evidence from cyclophilin D knockout mice.
In the present study, we have used a genetic mouse model that lacks cyclophilin D (CypD KO) to assess the cardioprotective effect of mitochondrial permeability transition pore (mPTP) inhibition on Ca2+ waves and Ca2+ alternans at the single cell level, and cardiac arrhythmias in whole-heart preparations. The protonophore carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) caused mitochondrial membrane potential depolarization to the same extent in cardiomyocytes from both WT and CypD KO mice, however, cardiomyocytes from CypD KO mice exhibited significantly less mPTP opening than cardiomyocytes from WT mice (p<0.05). Consistent with these results, FCCP caused significant increases in CaW rate in WT cardiomyocytes (p<0.05) but not in CypD KO cardiomyocytes. Furthermore, the incidence of Ca2+ alternans after treatment with FCCP and programmed stimulation was significantly higher in WT cardiomyocytes (11 of 13), than in WT cardiomyocytes treated with CsA (2 of 8; p<0.05) or CypD KO cardiomyocytes (2 of 10; p<0.01). (Pseudo-)Lead II ECGs were recorded from ex vivo hearts. We observed ST-T-wave alternans (a precursor of lethal arrhythmias) in 5 of 7 WT hearts. ST-T-wave alternans was not seen in CypD KO hearts (n=5) and in only 1 of 6 WT hearts treated with CsA. Consistent with these results, WT hearts exhibited a significantly higher average arrhythmia score than CypD KO (p<0.01) hearts subjected to FCCP treatment or chemical ischemia-reperfusion (p<0.01). In conclusion, CypD deficiency- induced mPTP inhibition attenuates CaWs and Ca2+ alternans during mitochondrial depolarization, and thereby protects against arrhythmogenesis in the heart.


Changes over time in audiometric thresholds in a group of automobile stamping and assembly workers with a hearing conservation program.
Noise induced hearing loss (NIHL) is among the 10 leading occupational diseases, afflicting between 7.4 and 10.2 million people who work in noise above 85 dBA. Although mandatory hearing conservation programs (HCPs) have been in effect since 1972, this problem persists, as hearing protectors are not consistently used by workers, or may not attenuate to manufacturer's estimates in real world conditions. In this study, information from noise and hearing protection use measurements taken at an automobile assembly plant were used to construct average lifetime noise exposure and hearing protection compliance estimates for use in modeling to predict both total hearing loss and onset of two accepted definitions of hearing loss. There were 301 males and females in this cohort; their mean age was 42.6 (7.2) years, and mean tenure was 14.3 (3.5) years. Average length of follow-up was 14.0 years. There were 16 members of this cohort who had hearing loss at the speech frequencies (defined as an average hearing level > or = 25 dB at 500, 1000, and 2000 Hz). In cross-sectional multivariate analyses, years of employment, male gender, and proportion of time wearing hearing protection were the factors most associated with hearing loss at the average of 2000, 3000, and 4000 Hz (p < 0.0001) controlling for age, transfer status (as a surrogate for previous noise exposure), race, and lifetime average noise exposure. The most consistent predictor of hearing loss in both univariate and multivariate analyses was percentage of time having used hearing protection during the workers' tenure.


Charging and Aggregation Behavior of Cellulose Nanofibers in Aqueous Solution.
To understand the charging and aggregation of cellulose nanofibers (CNFs), we performed the following experimental and theoretical studies. The charging behavior of CNFs was characterized by potentiometric acid-base titration measuring the density of deprotonated carboxyl groups at different KCl concentrations. The charging behavior from the titration was quantitatively described by the 1-pK Poisson-Boltzmann (PB) model for a cylinder. The electrophoretic mobility of CNFs was measured as a function of pH by electrophoretic light scattering. The mobility was analyzed with the equation for an infinitely long cylinder considering the relaxation of the electric double layer. Good agreement between experimental mobilities and theoretical calculation was obtained by assuming a reasonable distance from the surface to the slipping plane. The result demonstrated that the negative charge of CNFs originates from the deprotonation of β(1-4)-d-glucuronan on the surface. The aggregation behavior of CNFs was studied by measuring the hydrodynamic diameter of CNFs at different pH and KCl concentrations. Also, we calculated the capture efficiencies of aggregation, using interaction energies of perpendicularly and parallelly oriented cylinders. The interaction energies between cylinders in both orientations were obtained by the Derjaguin, Landau, Verwey, and Overbeek theory, where the electrostatic repulsion was calculated from the surface potential obtained by the 1-pK PB model. From comparison of the theoretical capture efficiency with the measured hydrodynamic diameter, we suggest that CNFs can be aggregated in perpendicular orientation at low pH and low salt concentration, and the fast aggregation regime of CNFs is realized by the reduction of electric repulsion for both perpendicularly and parallelly interacting CNFs. Meanwhile, the application of Smoluchowski's equation to the mobility of CNFs results in the underestimation of the zeta potential.


Morning magnesiuria: relation to age and sex.
Magnesium, calcium and creatinine concentration were assessed in the morning urine sample of 1710 subjects randomly selected from the population register in the Czech Republic: children aged 6, 10 and 13 years old and adults in age groups 18-35 years, 36-50 years, and 51-65 years of adults. The groups comprised 911 females and 799 males. There was a marked impact of age on the urinary magnesium concentration in both sexes, the concentration declining with advancing age. The child groups differed significantly from the adults. The urinary magnesium/creatinine ratio declined with age with the exception of the oldest group. The urinary calcium concentration did not change significantly with age in women or men. There was a weak age dependence in the calcium/creatinine ratio.


Synthesis, crystal structure, and photoluminescence of homodinuclear lanthanide 4-(dibenzylamino)benzoate complexes.
Three new binuclear lanthanide complexes of general formula [Ln(2)(L)(6)(H(2)O)(4)] (Ln = Tb (1), Eu (2), and Gd (3)) supported by the novel aromatic carboxylate ligand 4-(dibenzylamino)benzoic acid (HL) have been synthesized. Complexes 1 and 2 were structurally characterized by single-crystal X-ray diffraction. Both 1 and 2 crystallize in the triclinic space group P(1), and their molecular structures consist of homodinuclear species that are bridged by two oxygen atoms from two carboxylate ligands via different coordination modes. The discrete bridged dimer of 1 is centrosymmetric and features 8-coordinate terbium atoms, each of which adopts a distorted square-antiprismatic geometry. Both coordination spheres comprise two eta(2)-chelating benzoates, two mu-eta(1):eta(1)-carboxylate interactions from the bridging benzoates, and two water molecules. By contrast, in complex 2, the Eu(3+) ion coordination environment is best described as a distorted tricapped-trigonal prism, each europium ion being coordinated to three eta(2)-chelating benzoate ligands and two water molecules. One of the eta(2)-carboxylate ligands is involved in a further interaction with an adjacent metal, thus rendering the overall binding mode bridging tridentate, mu-eta(2):eta(1). Scrutiny of the packing diagrams for 1 and 2 revealed the existence of a one-dimensional molecular array that is held together by intermolecular hydrogen-bonding interactions. The Tb(3+) complex 1 exhibits high green luminescence efficiency in the solid state with a quantum yield of 82%. On the other hand, poor luminescence efficiency has been noted for the Eu(3+)-4-(dibenzylamino)benzoate complex.


Strong reproductive barriers in a narrow hybrid zone of West-Mediterranean green toads (Bufo viridis subgroup) with Plio-Pleistocene divergence.
One key question in evolutionary biology deals with the mode and rate at which reproductive isolation accumulates during allopatric speciation. Little is known about secondary contacts of recently diverged anuran species. Here we conduct a multi-locus field study to investigate a contact zone between two lineages of green toads with an estimated divergence time of 2.7 My, and report results from preliminary experimental crosses. The Sicilian endemic Bufo siculus and the Italian mainland-origin B. balearicus form a narrow hybrid zone east of Mt. Etna. Despite bidirectional mtDNA introgression over a ca. 40 km North-South cline, no F1 hybrids could be found, and nuclear genomes display almost no admixture. Populations from each side of the contact zone showed depressed genetic diversity and very strong differentiation (FST = 0.52). Preliminary experimental crosses point to a slightly reduced fitness in F1 hybrids, a strong hybrid breakdown in backcrossed offspring (F1 x parental, with very few reaching metamorphosis) and a complete and early mortality in F2 (F1 x F1). Genetic patterns at the contact zone are molded by drift and selection. Local effective sizes are reduced by the geography and history of the contact zone, B. balearicus populations being at the front wave of a recent expansion (late Pleistocene). Selection against hybrids likely results from intrinsic genomic causes (disruption of coadapted sets of genes in backcrosses and F2-hybrids), possibly reinforced by local adaptation (the ranges of the two taxa roughly coincide with the borders of semiarid and arid climates). The absence of F1 in the field might be due to premating isolation mechanisms. Our results, show that these lineages have evolved almost complete reproductive isolation after some 2.7 My of divergence, contrasting sharply with evidence from laboratory experiments that some anuran species may still produce viable F1 offspring after > 20 My of divergence.


Erythropoiesis signature and ubiquitin-mediated proteolysis are enriched in systematic juvenile idiopathic arthritis.
Systemic Juvenile Idiopathic Arthritis (sJIA) is a distinctive subtype of Juvenile Idiopathic Arthritis (JIA). The pathogenesis of sJIA is still unclear with the limited treatment options. Although previous bioinformatics analyses have identified some genetic factors underlying sJIA, these studies were mostly single centre with a small sample size and the results were often inconsistent. Herein, we combined two data sets of GSE20307 and GSE21521 and select the matrix of patients diagnosed as sJIA in it for further analysis. The GSE20307 and GSE21521 matrixes downloaded from the Gene Expression Omnibus (GEO) were analysed using online tools GEO2R, Venny, Metascape, STRING and Cytoscape to identify differentially expressed genes (DEGs), enrichment pathways, protein-protein interaction (PPI), main module and hub genes between sJIA individuals and healthy controls. A total of 289 overlapping genes (consisting of 41 downregulated genes and 248 upregulated genes) were identified. Hub genes were primarily related to erythropoiesis. And the KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis of overlapping DEGs were mainly involved in malaria and non-small cell lung cancer. Besides, DEGs in main module were involved in ubiquitin-mediated proteolysis. Our study suggests that the erythropoiesis signature indeed exists in sJIA similar to previous reports. And ubiquitin-mediated proteolysis is important in sJIA.


How Hydra senses and destroys microbes.
Molecular genetic evidence has revealed that the basic templates of innate immune sensors were laid down in ancient animals such as the cnidarian Hydra. Important functions of Hydra's innate immune sensors and effectors include not only protection against pathogens but also controlling tissue-microbiota homeostasis. The deep evolutionary connections imply that invertebrate and mammalian immune pathways have evolved from a reduced number of common ancestral building blocks to their present configurations.


Electro-Enhanced Separation of Microsized Oil-in-Water Emulsions via Metallic Membranes: Performance and Mechanistic Insights.
Conventional separation membranes suffer from evitable fouling and flux decrease for water treatment applications. Herein, a novel protocol of electro-enhanced membrane separation is proposed for the efficient treatment of microsized emulsions (∼1 μm) by rationally designing robust electroresponsive copper metallic membranes, which could mitigate oil fouling and coenhance permeance (from ∼1026 to ∼2516 L·m-2·h-1·bar-1) and rejection (from ∼87 to ∼98%). High-flux Cu membranes exhibit superior ductility and electrical conductivity, enabling promising electroactivity. Separation performance and the fouling mechanism were studied under different electrical potentials and ionic strengths. Application of negative polarization into a large-pore (∼2.1 μm) Cu membrane is favorable to not only almost completely reject smaller-sized oil droplets (∼1 μm) but also achieve antifouling and anticorrosion functions. Moreover, surfactants around oil droplets might be redistributed due to electrostatic repulsion, which effectively enhances the steric hindrance effect between neighboring oil droplets, mitigating oil coalescence and consequently membrane fouling. Furthermore, due to the screening effect of surfactants, the presence of low-concentration salts increases the adsorption of surfactants at the oil-water interface, thus preventing oil coalescence via decreasing oil-water interfacial tension. However, under high ionic strengths, the fouling mechanism converts from cake filtration to a complete blocking model due to the reduced electrostatic repulsion between the Cu membrane and oil droplets. This work would provide mechanistic insights into electro-enhanced antifouling for not only oil emulsion separation but also more water treatment applications using rationally designed novel electroresponsive membranes.


Evaluation of sufentanil anesthesia obtained by a computer-controlled infusion for cardiac surgery.
To determine the "therapeutic window" for sufentanil in cardiac surgery, nine hemodynamically stable, lightly premedicated patients were anesthetized with sufentanil to undergo coronary artery bypass grafting. Sufentanil was administered by a computer-controlled infusion pump programmed with an infusion scheme based on average sufentanil pharmacokinetics. The presence of somatic or hemodynamic responses to tracheal intubation, skin incision, sternotomy, and during electrocauterization, to isolate the internal mammary artery were correlated with plasma concentrations of sufentanil. The concentration versus response/no response relationships were analyzed by application of the logistic (Hill) equation. The CP50 of sufentanil to suppress responses to intubation, incision, and sternotomy was 7.1 ng/mL and for mediastinal dissection it was 12.7 ng/mL. Interpatient variability was as much as that reported previously for other opioids in other types of surgical patients. The computer-controlled infusion scheme consistently produced sufentanil plasma concentrations in excess of the target concentrations, but there was a strong correlation between target and actual sufentanil concentrations (r = 0.88, P < 0.05).


Carbofuran-induced endocrine disruption in adult male rats.
The objective of this investigation was to determine the acute toxic effects of the carbamate insecticide carbofuran on the levels of endocrine hormones in the serum of male Sprague-Dawley rats. Using chemiluminescent immunoassay, the hormones determined were progesterone, cortisol, estradiol, testosterone, triidothyronine (T3), total thyroxine (total T4), and non-protein-bound thyroxine (free T4). Rats exposed to an acute dose of carbofuran (1.5 mg/kg, s.c.) showed the onset of cholinergic signs (salivation, chewing, and fine tremors) within 5-7 min. With increasing intensity, toxic signs of maximal severity (severe convulsions and fasciculations) were observed within 30-60 min, and lasted for about 2 to 3 h. Time courses of hormones for 24 h revealed significant alterations in hormone levels during 0.5 to 3 h, with the exception of estradiol at 6 h. The levels of progesterone, cortisol, and estradiol were significantly increased (1279%, 202%, and 150%, respectively), while the levels of testosterone were decreased by 88%. No significant change occurred in thyroid hormones (T3, total T4, and free T4) at any time during the time course, despite the fact that body temperature was significantly low at 1 to 2 h after carbofuran injection. Carbofuran caused a >2-fold increase in glucose during early hours of toxicity. The results suggest that an acute exposure to carbofuran may cause transient endocrine disruption, which may consequently lead to serious reproductive problems following repeated exposure.


Density and frequency caudo-rostral gradients of sleep spindles recorded in the human cortex.
This study aims at providing a quantitative description of intrinsic spindle frequency and density (number of spindles/min) in cortical areas using deep intracerebral recordings in humans. Thirteen patients suffering from pharmaco-resistant focal epilepsy and investigated through deep intracortical EEG in frontal, parietal, temporal, occipital, insular, and limbic cortices including the hippocampus were included. Spindle waves were detected from the ongoing EEG during slow wave sleep (SWS) by performing a time-frequency analysis on filtered signals (band-pass filter: 10-16 Hz). Then, spindle intrinsic frequency was determined using a fast Fourier transform, and spindle density (number of spindles per minute) was computed. Firstly, we showed that sleep spindles were recorded in all explored cortical areas, except temporal neocortex. In particular, we observed the presence of spindles during SWS in areas such as the insular cortex, medial parietal cortex, occipital cortex, and cingulate gyrus. Secondly, we demonstrated that both spindle frequency and density smoothly change along the caudo-rostral axis, from fast frequent posterior spindles to slower and less frequent anterior spindles. Thirdly, we identified the presence of spindle frequency oscillations in the hippocampus and the entorhinal cortex. Spindling activity is widespread among cortical areas, which argues for the fundamental role of spindles in cortical functions. Mechanisms of caudo-rostral gradient modulation in spindle frequency and density may result from a complex interplay of intrinsic properties and extrinsic modulation of thalamocortical and corticothalamic neurons.


Spontaneous Hemoperitoneum From a Ruptured Gastrointestinal Stromal Tumor.
This is a case report of a ruptured gastrointestinal stromal tumor (GIST) presenting as spontaneous hemoperitoneum. The patient was a 63-year-old female with a past medical history of hypertension and ulcerative colitis who presented to the emergency department with worsening epigastric pain. The patient denied history of trauma, previous surgeries, or forceful vomiting. She was not on anticoagulation. Vital signs at presentation were stable. A CT scan of abdomen/pelvis revealed a large amount of fluid in the upper abdomen with high attenuation material adjacent to the greater curvature of the stomach concerning for hemoperitoneum. Diagnostic laparoscopy revealed a significant amount of blood along the upper abdominal viscera. The procedure was converted to an upper midline laparotomy after identifying a necrotic, extremely friable 7 x 6 x 3 cm pedunculated mass with active hemorrhage on the posterior aspect of the greater curvature. A wedge resection was performed to remove the mass with grossly negative margins. An intraoperative frozen section revealed a stromal tumor with spindle cells. Final pathology revealed a pT3N0M0 stromal tumor with histologic spindle cells and a high mitotic rate (24/5 mm2) consistent with a high-grade GIST. Given tumor rupture at presentation, the patient was started on imatinib therapy for a minimum duration of three years. GISTs are often asymptomatic or cause mild abdominal pain or GI bleeding. Rarely, an exophytic GIST may rupture leading to intraperitoneal bleeding. Surgical resection with negative margins is the mainstay of treatment although patients presenting with tumor rupture are at higher risk of dissemination and recurrence.


Mechanistic Studies on Garratt-Braverman Cyclization: The Diradical-Cycloaddition Puzzle.
In this work, we present the results of extensive multiprong studies involving the fate of deuterium-labeled substrates, EPR, trapping experiments, and LA-LDI mass spectrometry to sort out the controversies relating to the mechanism of Garratt-Braverman cyclization in two systems, namely bis-propargyl sulfones and ethers. The results are in conformity with a diradical mechamism for the sulfone, while for the ether, the anionic [4 + 2] appears to be the preferred pathway. This shows that the mechanistic pathway toward GB cyclization is dependent upon the nature of heteroatom (O or S in sulfone) bridging the propargyl arms.


Efficacy of Emu Oil Transfersomes for Local Transdermal Delivery of 4-OH Tamoxifen in the Treatment of Breast Cancer.
Oral tamoxifen used in the prevention and treatment of ductal carcinoma in situ (DCIS) (estrogen-positive) patients has limited acceptance, due to its adverse side effects. The efficacy of tamoxifen is related to its major metabolite, 4-hydroxytamoxifen. Local transdermal therapy of 4-hydroxytamoxifen to the breast might avert the toxicity of oral tamoxifen, while maintaining efficacy. We aim to study the skin irritancy, as well as to evaluate the efficacy of the developed transfersome formulations, with/without emu oil, using a syngeneic mouse model of breast cancer. We also quantified tamoxifen/4-hydroxytamoxifen concentrations in blood plasma and performed histopathology. The skin irritancy test showed that the pure emu oil and transfersome formulations with or without the emu oil did not cause skin irritancy in the animals studied. A sensitive and specific LC-MS/MS method for the quantification of tamoxifen and 4-hydroxytamoxifen was developed and validated. Studies on tumor volume and necrosis (histopathology) using the breast cancer mouse model showed that the 4-OHT transfersomal formulations, with and without emu oil, showed comparable efficacy with that of orally administered tamoxifen. However, the transfersomal formulations, with and without emu oil, resulted in significantly lower (10.24 ± 0.07 and 32.45 ± 0.48 ng/mL, respectively) plasma concentrations of 4-hydroxytamoxifen, compared to the oral tamoxifen (TAMX) group (634.42 ± 7.54 ng/mL). This study demonstrated the potential use of emu oil in a local transdermal formulation for the treatment of breast cancer and its reduced adverse effects.


Blocking ovarian cancer progression by targeting tumor microenvironmental leukocytes.
Current therapies for metastatic ovarian carcinoma are based on surgical debulking followed by chemotherapy. After more than three decades implementing treatments that selectively target the tumor cell, the 5-year survival rate for metastatic ovarian cancer patients is still lower than 30%. Novel strategies are therefore urgently needed to complement classical treatments for this malignancy. Recently, leukocytes in the ovarian cancer microenvironment such as regulatory T cells and immature pro-angiogenic/tolerogenic myeloid cells have been demonstrated to play a fundamental role in tumor progression. This review focuses on our recent understanding of the potential of eliminating and/or modulating the phenotype of these leukocytes in vivo and in situ as a novel intervention to complement standard ovarian cancer treatments. The significant effects of targeting these crucial microenvironmental players on cancer vascularization, local tumor growth, distal metastatic spreading and spontaneous anti-tumor immune responses are discussed.