Developing musculoskeletal education programs for physicians and the general public: findings from a needs assessment.
To assess the educational needs and learning preferences of primary care physicians and the general public in receiving musculoskeletal health education. Prospective surveys were mailed simultaneously to 2,250 primary care physicians and 2,250 members of the general public. The surveys included questions about demographics, motivation for attending programs, and preferred education program formats. The 68 responding physicians attend continuing medical education programs mainly based on topics, speakers, and timing. They prefer lectures and find question and answer sessions least helpful in supporting learning. The 96 responding members of the general public attend programs mainly based on topics, speakers, and fees. The general public stated that question and answer sessions best support learning in programs. A large percentage of responding physicians provide health education to their patients, but a small percentage of the general public respondents stated that they receive health education from physicians. Responses from physicians and the general public were generally not surprising but revealed interesting contrasts between learning preferences. While physicians and the general public both value speakers and topics, the physicians want to increase their knowledge about disease, whereas the general public wants practical information. Physicians and the general public also appear to take different approaches to learning. The contrast between availability and provision of health education is also striking. We cannot generalize our results with absolute confidence because the return rates for the surveys were so low. Nonetheless, we support the need to educate physicians and the general public in ways that match their preferred learning methods and educational needs.


Spontaneous abortion and physical strain around implantation: a follow-up study of first-pregnancy planners.
Existing studies of physical strain and spontaneous abortion are mainly retrospective or based only on pregnancies that have survived the first trimester. Furthermore, almost all studies have relied on averaged measures of physical strain, which tend to blur an effect if peak values during short time periods are the relevant measure. We followed a cohort of first pregnancy planners from termination of birth control until pregnancy for a maximum of six menstrual cycles. The analyses include 181 pregnancies, of which 32 were subclinical pregnancies detected by hCG analysis only. During early pregnancy the women recorded physical strain prospectively in a structured diary. Physical strain around the time of implantation was associated with later spontaneous abortion. The adjusted risk ratio for women who reported physical strain higher than average at day 6 to 9 after the estimated date of ovulation was 2.5 (95% CI = 1.3-4.6).


Aortic stiffness in normal and hypertensive pregnancy.
The objective of this study was to examine whether aortic stiffness, as assessed by pulse wave analysis, could reliably discriminate between normal and hypertensive pregnancies. One hundred pregnant women were studied: five with severe pre-eclampsia, 27 with gestational hypertension, 14 with chronic hypertension and 54 with normal pregnancy. Central hemodynamic parameters were obtained by an applanation tonometry and included central aortic systolic blood pressure (CSBP), central aortic diastolic blood pressure (CDBP), augmentation pressure (AP), augmentation index (AIx), AIx corrected to a heart rate of 75 (AIx@75) and time to reflection (Tr). All measures of aortic stiffness, including AP, AIx and AIx@75 were significantly higher in women with gestational hypertension and pre-eclampsia compared with normal pregnancies and women with chronic hypertension (p < 0.05 for all comparisons). There were no significant differences between normal pregnancies and women with chronic hypertension (p > 0.05 for all comparisons). Tr was significantly shorter in women with pre-eclampsia and gestational hypertension compared with normal pregnancies (p < 0.05). Aortic stiffness, as assessed by pulse wave analysis, is significantly increased in women with pre-eclampsia and gestational hypertension but not in treated women with chronic hypertension. Pulse wave analysis has a potential as a screening tool in women at high risk for pre-eclampsia. The final role of this method should be determined in prospective studies.


Description and characteristics of a ''wave follower'' system for energy exchange studies in the vicinity of an air-water interface.
This paper describes the design, construction, and testing of an electromechanical servomechanism capable of responding to the vertical displacements of a wavy air-water interface. The device is to be used to maintain various probes at a fixed distance above or below the moving interface in a large wind-wave tank. The measurements so obtained will help to elucidate the mechanisms of mass, momentum, and energy transfer between air and water in the presence of waves. The dynamical characteristics of the wave follower are given. For frequencies below 9 Hz, it possesses a linear reponse characterized below 5 Hz by a 7.4 ms time lag. This is the sum of two time lags, 4.9 and 2.5 ms, which correspond, respectively, to the servomechanism itself and to the capacitance-type wave height measurement system. The maximum position error is found to be +/-2 mm for typical wave amplification by wind studies (maximum wave height of about 6 cm).


Flow cytometric DNA index, G-band karyotyping, and comparative genomic hybridization in detection of high hyperdiploidy in childhood acute lymphoblastic leukemia.
High hyperdiploid acute lymphoblastic leukemia in children is related to a good outcome. Because these patients may be stratified to a low-intensity treatment, we have investigated the sensitivity of flow cytometry (FCM), G-band karyotyping (GBK), and high-resolution comparative genomic hybridization (HR-CGH) in detecting high hyperdiploid leukemic clones. Twenty-six girls and 34 boys with acute lymphoblastic leukemia diagnosed in 1998 to 1999 were analyzed by FCM, GBK, and HR-CGH. The correlations between DNA indices obtained by FCM, GBK, and HR-CGH were significant (rs=0.61 to 0.77; P<0.001 for all comparisons). However, in 4 of 18 patients, high hyperdiploidy was overlooked by GBK or HR-CGH, and even when FCM was applied, 2 of 18 patients with high hyperdiploidy by GBK and/or HR-CGH were classified as nonhigh hyperdiploid. If high hyperdiploid subclones were included, FCM could detect all high hyperdiploid patients found by either GBK or HR-CGH, but would then in addition classify 15% to 20% of the remaining patients as high hyperdiploid. Thus, both GBK and HR-CGH overlook patients with high hyperdiploidy, and FCM only detects all high hyperdiploid patients if small high hyperdiploid clones are included. In addition, FCM detects patients with high hyperdiploid subclones, not detected by either GBK or HR-CGH, and the challenge remains to determine the prognosis of patients with such high hyperdiploid subclones.


Prevalence, timing, and haemodynamic correlates of prodromes in patients with vasovagal syncope induced by head-up tilt test.
To evaluate the prevalence, timing, and haemodynamic characteristics of prodromal symptoms in patients experiencing vasovagal syncope (VVS) during a head-up tilt test (HUT) potentiated with nitroglycerin, and their relationships with those reported before spontaneous episodes. Symptoms preceding HUT-induced syncope were recorded, together with heart rate (HR) and arterial blood pressure (BP) values, in 149 otherwise healthy and drug-free subjects with recurrent unexplained syncope. Head-up tilt test significantly increase the number of patients capable of recognizing the premonitory symptoms of VVS than before spontaneous episodes (96 vs. 79%; P<0.001). The nine most frequent symptoms were stratified into three groups on the basis of their characteristics: headache, hot flashes, and palpitations occurred more than 3 min before syncope, with a very slight reduction in BP; nausea, asthenia, diaphoresis, vertigo, and epigastric discomfort preceded syncope by 1-3 min and were associated with a slight reduction in BP; and blurred vision appeared the last minute before syncope and was characterized by the lowest BP and HR values. In comparison with spontaneous syncopal episodes, HUT allows the more frequent recognition of prodromes also providing useful information in terms of timing and haemodynamic characteristics of symptoms that may allow more tailored patient counselling.


Small bowel intussusception in symptomatic pediatric patients: experiences with 19 surgically proven cases.
Nineteen cases of surgically proven symptomatic pediatric small bowel intussusceptions (SBI) were retrospectively reviewed. Clinical presentations included vomiting (89.5%), abdominal pain and/or irritable crying (89.5%), fever (52.6%), bloody stools (26.3%), palpable abdominal masses (15.8%), hematemesis (10.5%), jaundice (5.3%), and seizures (5.3%). The duration between symptom onset and hospitalization ranged between 20 and 336 hours (average 75.8 hours). Two patients with suspected appendicitis and small bowel obstruction were operated on promptly. Sonograms revealed target lesions (average diameter 2.9 cm) suggestive of intussusception in 13 out of 17 patients, with 10 lesions located in the paraumbilical or left abdominal regions. Barium enemas in 12 of these 13 patients demonstrated no colonic lesions. Diagnosis and surgery were delayed in 16 patients (average delay = 32 hours). The remaining 1 patient with positive sonographic findings underwent early surgery after computed tomographic (CT) confirmation of SBI. Surgery revealed ileoileal intussusceptions in 11 patients, jejunojejunal in 4, jejunoileal in 3, and duodenojejunal in 1. Eight patients had lead points. Bowel complications (ischemia, necrosis, or perforation) occurred in 8 patients. The duration between symptom onset and surgery in patients with bowel complications was significantly longer than for patients without complications (p = 0.0026). In conclusion, delayed diagnosis and surgical treatment in symptomatic pediatric patients with SBI were common, leading to a high rate (42%) of bowel complications. Sonographic demonstration of a 2-3 cm target lesion, especially if paraumbilical or left abdominal, is suggestive of SBI and may obviate the need for a barium enema; however, CT is helpful for confirming SBI. In symptomatic SBI, once diagnosed, early surgical referral is strongly recommended.


Outbreak investigation of foot-and-mouth disease in cattle in Tigray region, Northern Ethiopia.
An investigation of a foot-and-mouth disease (FMD) outbreak was conducted between late October and mid-December 2019 in Tigray region. The outbreak investigation team collected epidemiological data from the six villages of Kafta Humera and Seharti Samre districts, including morbidity proportions, mortality proportions, and clinical signs, and cattle management and vaccination history were collected via participatory methods, including interviews and group discussions with local experts and farmers in Kafta Humera and reports from the district veterinarians in Seharti Samre. Twenty-two tissue samples were collected for laboratory confirmation. Overall, 4,299/9,811 (43.8%) and 13,654/16,921 (80.6%) cattle showed clinical signs for FMD in Kafta Humera and Seharti Samre, respectively. In Kafta Humera, the highest morbidity proportion was found in adult cows and heifers (48.1%), followed by 27.8% in oxen and 15.9% in calves. In Seharti Samre, the morbidity proportion was similar in all age groups at ~81%. No death of FMD-suspected cattle was reported throughout the outbreak. The serotype of foot-and-mouth disease virus (FMDV) identified by laboratory analysis differed between the two districts (serotype O in Kafta Humera and serotype A in Seharti Samre). We, therefore, suggest that the outbreaks in the two districts occurred independently from each other. Experts and farmers were interviewed and believed that the outbreak in Kafta Humera was most likely caused by interaction between cattle and wildlife from the surrounding Kafta Sheraro National Park, which share common grazing land. This outbreak investigation showed that FMD can cause devastating cattle morbidity. A regular vaccination program against the identified circulating FMDV serotypes with sufficient coverage is required to avoid future outbreaks.


"Picture-in-picture" endoscopic images in the microscope.
The authors describe a new piece of equipment that enables simultaneous monitoring of the endoscopic image and unilateral microscopic image; that is, "picture-in-picture" images for endoscope-assisted microsurgery. The system is simple and purely optical, consisting of light-weight semi-rigid fibers and a special adapter incorporated in the microscope. Throughout the initial neurosurgical procedures in which it was tested, the system proved particularly useful for inspecting the facial nerve behind the acoustic neurinoma and for observing the contact between arteries and the facial nerve during decompressive procedures for hemifacial spasm.


Early experiences with E-prescribing.
Most physicians understand that e-prescribing will reduce medical errors and will be perceived by patients as making the prescription process easier. However, they are skeptical about a number of things. They worry whether their office processes will be improved or streamlined; e-prescribing will interface seamlessly with their existing practice management software; training and support will be available; e-prescribing data will be seamlessly transferable to an electronic health record when they implement a more advanced clinical record system for their practice; and if they will achieve a return on investment. Early adopting clinicians in Massachusetts can convince the majority of clinicians to adopt e-prescribing by sharing their motivations for adopting e-prescribing, the challenges that they needed to overcome, the hardware and software requirements, and integration into their office workflow. Finally, interaction with the physicians and practice managers in the audience makes the adoption of e-prescribing seem both reasonable and exciting. Resources such as vendor lists, questions to ask, and hardware and software requirements also need to be readily available and in a form that non-technical staff can read and understand. Physicians who know the "why" would also like to know


Multi- To Single-Joint or the Reverse Exercise Order Does Not Affect Pectoralis Major Workout Performance.
The purpose of this study was to examine the acute effects of multi- to single-joint or the reverse exercise order on repetition performance and perceived exertion for the pectoralis major. Fourteen trained men (24.05 ± 4.17 yrs, 78.85 ± 3.51 kg, 175.42 ± 4.01 cm) underwent two different training sequences (SEQ1 and SEQ2). In SEQ1, all subjects performed 5 sets for maximal repetitions, with a 2-min rest interval, of the bench press followed by the machine chest fly with 10 repetitions maximum load. In SEQ2, the same procedures were repeated, but with the reverse order. The t-test did not show any differences (p = 0.140) in total workout repetitions between SEQ1 (62.22 ± 11.00 repetitions) and SEQ2 (55.40 ± 8.51 repetitions). Conversely, the total repetition number for the bench press exercise was significantly greater (p = 0.001) following SEQ1 (34.36 ± 4.68 repetitions) compared to SEQ2 (25.85 ± 6.73 repetitions). In contrast, the total repetition number for the machine chest fly exercise following SEQ2 was significantly greater (p = 0.001) (33.50 + 4.11 repetitions) compared to SEQ1 (27.85 ± 6.52 repetitions). Despite no significant differences found for the rating of perceived exertion (RPE) values between SEQ1 and SEQ2 for the barbell bench press in all sets (p ≥ 0.083), significantly higher RPE values for the machine chest fly were observed over the first three sets following SEQ1 compared to SEQ2 (p < 0.01). In conclusion, the total workout repetitions were not significantly different when performing the traditional multi- to single-joint or the reverse exercise order when training the pectoralis major muscle.


Synergistic effects of antigen and soluble T-cell factors in B-lymphocyte activation.
Supernatants from phorbol 12-myristate 13-acetate-activated cultures of the mouse EL4 thymoma, or of several mouse T-cell hybridomas stimulated either by their specific antigen or by concanavalin A, induced primary splenic B cells to proliferate and differentiate to antibody-secreting cells. This effect was not due to interleukin 2 and did not require the presence of macrophages. The antibody response was polyclonal, including antibodies specific for 2,4-dinitrophenyl and pigeon cytochrome c, present in amounts of 1% or less of the total immunoglobulin produced. The addition of either of these antigens increased the amount of the corresponding specific antibody. At very high concentrations of dinitrophenyl-hemocyanin the specific response could be depressed. These observations were taken to demonstrate that soluble T-cell factors are sufficient to activate a portion of naive B cells to antibody secretion and that under these conditions in vitro the presence of antigen merely enhances the specific response.


Gene deletions in Arab patients with spinal muscular atrophy.
Spinal muscular atrophy is an autosomal recessive disorder characterized by degeneration of lower motor neurons. We have investigated the presence of survival motor neuron gene and neuronal apoptosis inhibitory protein gene deletions in 17 Arab and 1 Indian families with spinal muscular atrophy (15 type I and 3 type II). Homologous deletions were detected in exons 7 and 8 of the survival motor neuron gene and exon 5 of the neuronal apoptosis inhibitory protein gene in all patients with type I spinal muscular atrophy. Exon 13 of the neuronal apoptosis inhibitory protein gene was deleted in only one patient with type I spinal muscular atrophy. In two patients with type II spinal muscular atrophy, only exons 7 and 8 of the survival motor neuron gene were deleted whereas exons 5 and 13 of the neuronal apoptosis inhibitory protein gene were present. In another patient with spinal muscular atrophy type II, exons 7 and 8 of the survival motor neuron gene and exon 5 of the neuronal apoptosis inhibitory protein gene were deleted. This latter patient also had the Pierre Robin syndrome. No deletion was detected in healthy siblings or the parents. The deletions found in our patients are similar to those reported in other population groups.


Upsides and downsides of a telecounselling model of integrated asthma management between general practitioners and specialists.
Asthma control, one of the most important goals in the management of asthmatic patients, requires good adherence to guidelines and support at a territorial level, in particular on the part of general practitioners (GPs). A territorial hospital alliance can become a strength in asthma management, where control by GPs can also be carried out through a spirometric examination. The realisation of a telecounselling model management of asthma between GPs and specialists was the aim of this study, to understand how to obtain good asthma control. A specific digital platform, the PneumoApp platform, was used for the insertion of clinical data and flow volume (F-V) curves, performed in asthmatic patients by GPs, and for the subsequent evaluation of these data by specialists. GPs have shown to be able to perform a check-up of respiratory function well using a portable spirometer, but the analysis of the collected data showed that GP assessment of the severity level of asthma is incorrect in patients with moderate-severe asthma. The effectiveness of a telecounselling collaboration between hospital and territory in the management of asthma patients can be improved by greater diffusion of the use of Global Initiative for Asthma (GINA) guidelines at a local level.


Combined mental task and metaboreflex impair cerebral oxygenation in patients with type 2 diabetes mellitus.
Cardiovascular regulation is altered by type 2 diabetes mellitus (DM2), producing an abnormal response to muscle metaboreflex. During physical exercise, cerebral blood flow is impaired in patients with DM2, and this phenomenon may reduce cerebral oxygenation (COX). We hypothesized that the simultaneous execution of a mental task (MT) and metaboreflex activation would reduce COX in patients with DM2. Thirteen individuals suffering from DM2 (6 women) and 13 normal age-matched controls (CTL, 6 women) participated in this study. They underwent five different tests, each lasting 12 min: postexercise muscle ischemia (PEMI) to activate the metaboreflex, control exercise recovery (CER), PEMI + MT, CER + MT, and MT alone. COX was evaluated using near-infrared spectroscopy with sensors applied to the forehead. Central hemodynamics was assessed using impedance cardiography. We found that when MT was superimposed on the PEMI-induced metaboreflex, patients with DM2 could not increase COX to the same extent reached by the CTL group (101.13% ± 1.08% vs. 104.23% ± 2.51%, P < 0.05). Moreover, patients with DM2 had higher mean blood pressure and systemic vascular resistance as well as lower stroke volume and cardiac output levels compared with the CTL group, throughout our experiments. It was concluded that patients with DM2 had reduced capacity to enhance COX when undertaking an MT during metaboreflex. Results also confirm that patients with DM2 had dysregulated hemodynamics during metaboreflex, with exaggerated blood pressure response and vasoconstriction. This may have implications for these patients' lack of inclination to exercise.


Routine diagnostic patch-testing with formaldehyde 2.0% (0.6 mg/cm2) may be an advantage compared to 1.0%.
Our clinical experience has suggested that the presently recommended patch-test concentration (1.0%) for formaldehyde in the baseline series might be too low. Therefore, consecutively patch-tested dermatitis patients were tested simultaneously with formaldehyde 1.0% and 2.0% (w/v) in aqua. Formaldehyde 1.0% and 2.0% were applied with a micro-pipette (15 microl) to filter paper discs in Finn Chambers (0.30 mg/cm(2) and 0.60 mg/cm(2), respectively). A total of 1397 patients with dermatitis were patch-tested. In all, 68 (4.9%) patients reacted positively to formaldehyde; 37 reacted only to 2.0%, 29 reacted to both concentrations, and 2 reacted only to 1.0%. Significantly more patients were thus diagnosed with contact allergy to formaldehyde 2.0% compared with 1.0% (p < 0.001). We detected 0.1%, 0.4%, and 29.6% irritant reactions to 1.0%, 2.0%, and 3.0% formaldehyde, respectively. We conclude that, with an optimized patch-test technique, doubling the dose per area detects significantly more contact allergies to formaldehyde, but an even higher test concentration causes too many irritant reactions to be usable.


Rhodium-Catalyzed C-H Annulation of Nitrones with Alkynes: A Regiospecific Route to Unsymmetrical 2,3-Diaryl-Substituted Indoles.
The direct C-H annulation of anilines or related compounds with internal alkynes provides straightforward access to 2,3-disubstituted indole products. However, this transformation proceeds with poor regioselectivity in the synthesis of unsymmetrically 2,3-diaryl substituted indoles. Herein, we report the rhodium(III)-catalyzed C-H annulation of nitrones with symmetrical diaryl alkynes as an alternative method to prepare 2,3-diaryl-substituted N-unprotected indoles with two different aryl groups. One of the aryl substituents is derived from N=C-aryl ring of the nitrone and the other from the alkyne substrate, thus providing the indole products with exclusive regioselectivity.


X-ray-verified fractures are associated with finite element analysis-derived bone strength and trabecular microstructure in young adult men.
It has been suggested that fracture during childhood could be a predictor of low peak bone mass and thereby a potential risk factor for osteoporosis and fragility fractures later in life. The aim of this cross-sectional, population-based study was to investigate whether prevalent fractures, occurring from birth to young adulthood, were related to high-resolution peripheral quantitative computed tomography (HR-pQCT)-derived trabecular and cortical microstructure, as well as bone strength estimated by finite element (FEA) analysis of the radius and tibia in 833 young adult men around the time of peak bone mass (ages 23 to 25 years). In total, 292 subjects with prevalent X-ray-verified fractures were found. Men with prevalent fractures had lower trabecular bone volume fraction (BV/TV) at the radius (5.5%, p < 0.001) and tibia (3.7%, p < 0.001), as well as lower cortical thickness (5.1%, p < 0.01) and cortical cross-sectional area (4.1%, p < 0.01) at the tibia. No significant differences were seen for the cortical porosity or mean pore diameter. Using a logistic regression model (including age, smoking, physical activity, calcium intake, height, and weight as covariates), every SD decrease of FEA-estimated failure load was associated with an increased prevalence of fractures at both the radius (odds ratio [OR] 1.22 [1.03-1.45]) and tibia (OR 1.32 [1.11-1.56]). Including dual-energy X-ray absorptiometry (DXA)-derived radius areal bone mineral density (aBMD), cortical thickness, and trabecular BV/TV simultaneously in a logistic regression model (with age, smoking, physical activity, calcium intake, height, and weight as covariates), BV/TV was inversely and independently associated with prevalent fractures (OR 1.28 [1.04-1.59]), whereas aBMD and cortical thickness were not (OR 1.19 [0.92-1.55] and OR 0.91 [0.73-1.12], respectively). In conclusion, prevalent fractures in young adult men were associated with impaired trabecular BV/TV at the radius, independently of aBMD and cortical thickness, indicating that primarily trabecular bone deficits are of greatest importance for prevalent fracture in this population.


Shape of the absorption and fluorescence spectra of condensed phases and transition energies.
General integral expressions for the temperature-dependent profile of the spectral lines of photon absorption and emission by atomic or molecular species in a condensed environment are derived with no other hypothesis than: (a) The acoustic vibrational modes of the condensed host medium constitute the thermodynamic energy reservoir at a given constant temperature, and local electronic transitions modifying the equilibrium configuration of the surroundings are multiphonon events, regardless of the magnitude of the transition energy. (b) Electron-phonon coupling is linear in the variations of the bond length. The purpose is to develop a theoretical tool for the analysis of the spectra, allowing us to grasp highly accurate information from fitting the theoretical line shape function to experiment, including those spectra displaying wide features. The method is illustrated by applying it to two dyes, Lucifer Yellow CH and Coumarin 1, which display fluorescence maxima of 0.41 and 0.51 eV fwhm. Fitting the theoretical curves to the spectra indicates that the neat excitation energies are 2.58 eV ± 2.5% and 3.00 eV ± 2.0%, respectively.


Assessment of a new biological complex efficacy on dysseborrhea, inflammation, and Propionibacterium acnes proliferation.
Acne vulgaris is a common chronic inflammatory disease of the pilosebaceous unit triggered by Propionibacterium acnes. A bakuchiol, Ginkgo biloba extract, and mannitol (BGM) complex has been developed to provide patients with acne with a specific dermocosmetic to be used adjunctively with conventional treatments. The aim of these studies was to assess the antibacterial, anti-inflammatory, and antioxidative potential of BGM complex and its individual compounds as well as its impact on sebum composition. The antibacterial, anti-inflammatory, and antioxidative potential of BGM complex and its compounds was assessed through in vitro, ex vivo, and clinical studies. The clinical benefit of BGM complex formulated in a cream was assessed in subjects prone to acne through sebum composition analysis and photometric assessments. Results from the studies showed that the BGM complex has significant antibacterial, anti-inflammatory, and antioxidative properties. At similar concentrations, bakuchiol has up to twice the antioxidative potential than vitamin E. In subjects, BGM complex regulated the sebum composition in acne patients by increasing the level of sapienic and linolenic acid and reducing the level of oleic acid. The reduced number of porphyrins on the skin surface showed that it is also effective against P. acnes. BGM complex provides a complete adjunctive care in patients with acne by targeting etiopathogenic factors of acne: dysseborrhea, inflammation, and P. acnes proliferation.


Recombination mechanisms of luminescence type gas sensors.
Luminescence type gas sensors based on organic luminophores are characterized by an excellent signal stability over the luminophores' lifetime. Even though the sensing material is prone to degradation due to photobleaching, evaluation of the dynamic optical response allows to minimize aging induced drift effects of the luminophore and the optoelectronic components. The gas dependent luminophore decay time is mostly independent of the excitation intensity, which is attributed to the monomolecular recombination in many organic luminophores. To improve the overall sensor lifetime and to utilize this luminescence based sensor concept for long-term sensing applications, new luminophores are needed. Potential candidates are inorganic, semiconducting materials, which, however, show more complex recombination behaviour than the organic luminophores mentioned before, involving also bimolecular recombination. In the scope of this work, the differences of mono- and bimolecular recombination are discussed by the use of a simple statistical model. The theoretical aspects are furthermore confirmed by dynamic luminescence measurements on manganese doped zinc sulfide (ZnS). The semiconducting ZnS is an oxygen sensitive luminophore, which shows both, mono- and bimolecular recombination, depending on the excitation energy.


P-glycoprotein versus MRP1 on transport kinetics of cationic lipophilic substrates: a comparative study using [99mTc]sestamibi and [99mTc]tetrofosmin.
The multidrug resistance (MDR) phenotype in cancer is closely related with the overexpression of P-glycoprotein (Pgp) and multidrug resistance protein-1 (MRP1). Although conferring resistance to a similar spectrum of drugs, these proteins present distinct transport mechanisms and have their own substrates. In this work, we compared the functional properties of Pgp and MRP1 in the transport kinetics of two cationic lipophilic tracers, [(99m)Tc]sestamibi and [(99m)Tc]tetrofosmin, in cellular models of resistance. Cellular transport kinetics of both tracers was evaluated in Small-cell lung cancer cell line H69 and in its drug-resistant sublines, H69LX4 and H69AR, overexpressing Pgp and MRP1, respectively. Studies were performed in the absence and in the presence of MDR modulators. Kinetic parameters extracted from time-activity curves were analyzed through receiver-operating characteristics curve analysis. The uptake and the efflux rate of both radiotracers were significantly higher (p < 0.05) in sensitive cells. However, MRP1 was more effective than Pgp in removing tracers from the intracellular medium. The addition of verapamil and PSC833 significantly reduced the efflux rate and restored the accumulation of both tracers in H69LX4 cells. Only verapamil was effective in the inhibition of MRP1; however, the effects were more pronounced with [(99m)Tc]sestamibi, when compared to [(99m)Tc]tetrofosmin. Outward transport of radiotracers by MRP1 was dependent on the intracellular glutathione levels. We concluded that both tracers can detect Pgp- and MRP1-mediated drug resistance, based on transport kinetics; however, MRP1 is more effective than Pgp on outward transport of radiotracers. We postulate that this finding can be useful to distinguish between the two resistance mechanisms.


Hydrogen sulfide toxicity in a thermal spring: a fatal outcome.
Hydrogen sulfide (H(2)S) is a toxic gas with the smells of "rotten egg"; its toxic effects are due to the blocking of cellular respiratory enzymes leading to cell anoxia and cell damage. We report two cases with acute H(2)S intoxication caused by inhalation of H(2)S evaporated from the water of a thermal spring. Two victims were found in a hotel room were they could take a thermal bath. A 26-year-old male was found unconscious; he was resuscitated, received supportive treatment and survived. A 25-year-old female was found dead. Autopsy showed diffuse edema and pulmonary congestion. Toxicological blood analysis of the female revealed the following concentrations: 0.68 mg/L sulfide and 0.21 mmol/L thiosulfate. The urine thiosulfate concentration was normal. Forensic investigation established that the thermal water was coming from the hotel's own illegal well. The hotel was closed. This report highlights the danger of H(2)S toxicity not only for reservoir and sewer cleaners, but also for individuals bathing in thermal springs.


Effect of dihydrostreptomycin or oxytetracycline on reproductive capacity of bulls.
Young beef bulls (n = 27) were used in a trial to study the effect of dihydrostreptomycin sulfate (DHS) or oxytetracycline (OTC) hydrochloride on spermatogenesis, epididymal sperm maturation, and freezability of sperm. Nine of the bulls were given a 22 mg/kg dose of DHS twice, 12 hours between doses. Nine other bulls were treated with OTC--1 dose of 26.4 mg/kg of body weight, and then 6 more doses each of 17.6 mg/kg, ca 12 hours between doses. The remaining 9 bulls were nontreated controls. The treatment regimens with the 2 antibiotics were without effect on spermatogenesis. These treatments also were without effect on seminal pH, ejaculate volume, percentage of motile spermatozoa, rate of spermatozoal motility, or concentration of spermatozoa in ejaculates harvested on day 3 or 7 of the study (day 0 = 1st day of treatment). There was a treatment-by-day effect on spermatozoal concentration; the number of sperm per milliliter was markedly increased on day 3 for OTC-treated bulls. The increased spermatozoal concentration in the OTC-treated group was associated with an influence of the antibiotic on ejaculation. All bulls given this antibiotic ejaculated without palpable penile engorgement or erection on day 3. On day 7 the rate of spermatozoal motility was increased in the 2 treatment groups compared with the rate in the control bulls. Also on day 7, the percentage of motile spermatozoa was greater in the OTC-treated bulls than in the control or DHS-treated bulls.(ABSTRACT TRUNCATED AT 250 WORDS)


Life events, stress appraisals, and hospital doctors' mental health.
To investigate psychological distress among Auckland Health Board hospital doctors, and to evaluate the unique relationships of idealism, stressful life events, and stress appraisals to their mental health. A questionnaire consisting of the General Health Questionnaire (GHQ-12), the Physician Stress Inventory of stress appraisals, the Social Readjustment Rating Scale, and demographic questions was distributed to 680 Auckland Hospital doctors; 172 (25.3%) of these doctors returned useable questionnaires. Psychological distress was defined by GHQ-12 global scores of current depression, anxiety, and psychiatric symptoms. Cases of psychological distress (29.1%) were comparable to those of GPs in New Zealand (NZ), Australia, and the United Kingdom (UK), and significantly higher than the general NZ population (although there were no demographic differences). Multivariate analysis of variance showed that, compared to non-cases, cases had higher mean stressful life-event scores and appraisal scores for internal professional stress, external professional stress, decreased work productivity, and interference with family life. Stepwise regression analysis revealed that life events and stress appraisals had a very large effect on psychological distress, with appraisals of decreased work productivity and interference with family life having significant effects. Stress appraisals need to be considered in examining the relationship between stressful situations and hospital doctors' mental health.


Preoperative and postoperative nipple-areola sensibility in patients undergoing reduction mammaplasty.
Objective data on nipple and areola sensibility are scarce. For women with macromastia, there is little published information available indicating the incidence and intensity of postoperative nipple and areola sensibility. This prospective study was undertaken to evaluate nipple and areola sensibility in "small-breasted" control subjects as well as in patients with macromastia before and after reduction mammaplasty. Preoperative and postoperative Semmes-Weinstein pressure threshold testing was performed on 84 breasts in 43 patients and on 12 breasts of A or B cup size in the control group. The patients underwent reduction mammaplasty by the central parenchymal pedicle technique or the laterally based inferior pedicle technique. Nipple-areola sensibility was retained in 96 percent of breasts when the excision of breast tissue was less than 550 gm and 85 percent of breasts when the excision was greater than 550 gm. Overall, nipple-areola sensibility was retained in 90.5 percent of the 84 breasts tested. In those breasts in which nipple-areola sensibility was retained after surgery, there was no statistical difference in the preoperative and postoperative Semmes-Weinstein pressure threshold values. When pressure threshold values were compared in patients who had less than 550 gm of tissue resected, patients who had greater than 550 gm of tissue resected, and controls who had not undergone surgery, the trend of decreasing nipple-areola sensibility with increasing breast size was clearly seen.


Transformation of the fungicide chlorothalonil by Fenton reagent.
A modified Fenton reagent (Fe(3+)/H(2)O(2)) transformed the fungicide chlorothalonil within 60 min in aqueous solution at unadjusted pH. Transformation varied with ferric salt. Transformation was greatest with ferric nitrate and least when ferric sulfate was used. UV irradiation enhanced the transformation of chlorothalonil. The transformation of chlorothalonil was enhanced, which increased with ferric ion or hydrogen peroxide concentration. Maximum transformation was achieved at 2 mM ferric ion and 100 mM hydrogen peroxide. Additionally, chlorothalonil was more dechlorinated in the UV irradiation condition. The proposed reaction pathway includes reduction of chlorothalonil to trichloroisophthalonitrile, dichloroisophthalonitrile, and monochloroisophthalonitrile; oxidation of trichloroisophthalonitrile to trichloro-3-cyanobenzoic acid and 3-carbamyltrichlorobenzoic acid; and oxidation of hydroxychlorothalonil to trichloro-3-cyanohydroxybenzoic acid and trichlorocyanophenol.


A conservative approach to granular cell tumors of the esophagus: four case reports and literature review.
We present here four patients with six granular cell tumors of the esophagus: all are women, 22, 38, 47, and 49 yr old. In three of them, single polyps were encountered. In the fourth, age 38, two lesions were found in 1982, and a new one, a satellite polyp, has appeared after 5 yr of follow-up. All of the patients' conditions were followed up [mean time 65 months (16 months to 10 yr)]. In connection with these case reports, we include an up-to-date review of the world literature on this subject.


islet reveals segmentation in the Amphioxus hindbrain homolog.
The vertebrate embryonic hindbrain is segmented into rhombomeres. Gene expression studies suggest that amphioxus, the closest invertebrate relative of vertebrates, has a hindbrain homolog. However, this region is not overtly segmented in amphioxus, raising the question of how hindbrain segmentation arose in chordate evolution. Vertebrate hindbrain segmentation includes the patterning of cranial motor neurons, which can be identified by their expression of the LIM-homeodomain transcription factor islet1. To learn if the amphioxus hindbrain homolog is cryptically segmented, we cloned an amphioxus gene closely related to islet1, which we named simply islet. We report that amphioxus islet expression includes a domain of segmentally arranged cells in the ventral hindbrain homolog. We hypothesize that these cells are developing motor neurons and reveal a form of hindbrain segmentation in amphioxus. Hence, vertebrate rhombomeres may derive from a cryptically segmented brain present in the amphioxus/vertebrate ancestor. Other islet expression domains provide evidence for amphioxus homologs of the pineal gland, adenohypophysis, and endocrine pancreas. Surprisingly, homologs of vertebrate islet1-expressing spinal motor neurons and Rohon-Beard sensory neurons appear to be absent.


Novel Sensor Tibial Inserts in Total Knee Arthroplasty: A Review.
Traditional techniques to balance total knee arthroplasties are often subject to variability, as they are usually based on the surgeon's subjective assessment. Improperly balanced total knee arthroplasties can cause complications such as stiffness, pain, or instability, which may ultimately result in a revision procedure. In an effort to mitigate this, a tibial insert sensor technology has recently been developed to allow for quantifiable, objective measurements of soft-tissue balancing. A systematic review of the current literature was performed, highlighting the utility of this sensor tibial insert with focus on: (1) compartment loading pressures; (2) component orientations; and (3) clinical outcomes.


Spread of Oropouche virus into the central nervous system in mouse.
Oropouche virus (OROV) is an important cause of arboviral illness in Brazil and other Latin American countries, with most cases clinically manifested as acute febrile illness referred to as Oropouche fever, including myalgia, headache, arthralgia and malaise. However, OROV can also affect the central nervous system (CNS) with clinical neurological implications. Little is known regarding OROV pathogenesis, especially how OROV gains access to the CNS. In the present study, neonatal BALB/c mice were inoculated with OROV by the subcutaneous route and the progression of OROV spread into the CNS was evaluated. Immunohistochemistry revealed that OROV infection advances from posterior parts of the brain, including the periaqueductal gray, toward the forebrain. In the early phases of the infection OROV gains access to neural routes, reaching the spinal cord and ascending to the brain through brainstem regions, with little inflammation. Later, as infection progresses, OROV crosses the blood-brain barrier, resulting in more intense spread into the brain parenchyma, with more severe manifestations of encephalitis.


Effects of tryptophan depletion on Poggendorff illusion, corner Poggendorff illusion, and attention.
The effects of a tryptophan-free amino acid mixture on Poggendorff illusion, corner Poggendorff illusion, and attention were investigated with 12 male subjects who ingested either a balanced amino acid mixture or a tryptophan-free mixture, the latter known to cause a marked depletion of brain tryptophan and serotonin. No significant difference between the two mixtures on the perceptual illusions was found.


Ready-to-Use Colorimetric Platform for Versatile Enzyme Assays through Copper Ion-Mediated Catalysis.
A low cost and versatile colorimetric platform is developed for selective detections of various enzymes. Similar to peroxidases, free copper ion catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2 and turns TMB into a blue product. Bindings from ligands toward copper ions inhibit this catalysis. Enzymes catalyze the reactions of related substrates with generation or consumption the ligands for the binding and thus in turn alter the color changes as responses toward the enzymes. With suitable substrates, exemplary enzymes, including trypsin, acid phosphatase, and tyrosinase, can be sensitively measured, with limits of detection of 0.003 μg/mL, 0.004 U/L, and 0.02 U/mL, respectively. This platform is built with directly available reagents, and the signals can be obtained with inexpensive photometers or visual observations. The low cost and convenience make it suitable for cases where complicated instrumentations are not available, such as point-of-care testing.


Old and new therapeutic strategies in systemic sclerosis (Review).
Systemic sclerosis (SSc) is a chronic inflammatory disease with autoimmune determinism having an incompletely known pathogenesis. Although not all links in the pathogenic chain are known, studies have shown that vasculopathy is the initial event and is followed by extensive fibrosis of the skin and internal organs. New therapeutic strategies have been developed in recent years, thanks to innovative research which has increased understanding of the disease mechanisms. No curative treatment for SSc is currently known. Therefore, the therapeutic target in SSc is its symptomatology. Peripheral vasculopathy can be improved by administering vasodilators. Endothelin receptor antagonists and 5-phosphodiesterase inhibitors have a double benefit, both on peripheral and on pulmonary vasculopathy. Several molecules with antifibrotic effects are currently available; however, further studies are needed to confirm their beneficial effects. Immunosuppressants manage to control the cutaneous and visceral fibrotic process, thereby remaining as first-line drugs in the treatment of SSc. Although biological therapy using rituximab and tocilizumab has shown promising results in pulmonary fibrosis, ongoing studies are needed to determine their exact impact. The authors have differing views on the triggering role of glucocorticoids and the benefits of angiotensin-converting enzyme inhibitors in renal scleroderma. Some aspects of this disease such as calcinosis and pruritus, asthenia, or joint and muscle damage, remain difficult to manage.


Lacune and Large Perivascular Space: Two Kinds of Cavities Are of Different Risk Factors and Stroke Risk.
To compare the risk factors and risk of stroke between lacune and large perivascular spaces (PVSs) in a community-based sample. Large PVSs were assessed using 3.0T MRI in a population-based cohort consisting of 1,204 participants. The relationship between cardiovascular risk factors, neuroimaging changes, and incidental stroke risk and the presence of lacune or large PVSs was assessed with univariate and multivariable ordinal logistic regression analysis. Of the 1,204 study participants (55.7 ± 9.3 years, 37.0% men), a total of 347 large PVSs were detected in 235 (19.5%) subjects, while a total of 219 lacunes were detected in 183 subjects (15.2%). The presence of lacunes was found to be significantly associated with age, male gender, hypertension, and diabetes, whereas only age (p < 0.01) and ApoEε4 carrier status (p < 0.01) were related to the presence of large PVSs. Those who had lacunes detected on MRI at baseline had a significant increased risk of stroke (hazard ratio [HR] 4.68; 95% confidence interval [CI], 1.15-19.07) during the 3-year follow-up independent of age, gender, and other vascular risk factors. However, there was no significant relationship between the presence of large PVSs and incident stroke (HR 3.84; 95% CI, 0.82-18.04). The lack of association between large PVSs and cardiovascular risk factors or risk of stroke indicated a nonvascular pathogenic mechanism underlying large PVSs, suggesting the importance of distinguishing large PVSs from lacunes in clinical practice.


Growth and ligninolytic system production dynamics of the Phanerochaete chrysosporium fungus A modelling and optimization approach.
The well-documented ability to degrade lignin and a variety of complex chemicals showed by the white-rot fungus Phanerochaete chrysosporium has made it the subject of many studies in areas of environmental concern, including pulp bioleaching and bioremediation technologies. However, until now, most of the work in this field has been focused on the ligninolytic sub-system but, due to the great complexity of the involved processes, less progress has been made in understanding the biochemical regulatory structure that could explain growth dynamics, the substrate utilization and the ligninolytic system production itself. In this work we want to tackle this problem from the perspectives and approaches of systems biology, which have been shown to be effective in the case of complex systems. We will use a top-down approach to the construction of this model aiming to identify the cellular sub-systems that play a major role in the whole process. We have investigated growth dynamics, substrate consumption and lignin peroxidase production of the P. chrysosporium wild type under a set of definite culture conditions. Based on data gathered from different authors and in our own experimental determinations, we built a model using a GMA power-law representation, which was used as platform to make predictive simulations. Thereby, we could assess the consistency of some current assumptions about the regulatory structure of the overall process. The model parameters were estimated from a time series experimental measurements by means of an algorithm previously adapted and optimized for power-law models. The model was subsequently checked for quality by comparing its predictions with the experimental behavior observed in new, different experimental settings and through perturbation analysis aimed to test the robustness of the model. Hence, the model showed to be able to predict the dynamics of two critical variables such as biomass and lignin peroxidase activity when in conditions of nutrient deprivation and after pulses of veratryl alcohol. Moreover, it successfully predicts the evolution of the variables during both, the active growth phase and after the deprivation shock. The close agreement between the predicted and observed behavior and the advanced understanding of its kinetic structure and regulatory features provides the necessary background for the design of a biotechnological set-up designed for the continuous production of the ligninolityc system and its optimization.


Mesial atrophy and outcome after amygdalohippocampectomy or temporal lobe removal.
We studied 74 consecutive patients with temporal lobe epilepsy who were treated surgically and in whom the volumes of mesial temporal structures were determined preoperatively by magnetic resonance imaging. We divided the patients into three groups according to the volumetric findings: unilateral (63.5% of the patients), bilateral (23%), or no atrophy (13.5%) of the amygdala-hippocampal formation. Two distinct surgical approaches were used: selective amygdalohippocampectomy (n = 37) or anterior temporal lobe resection (n = 37). Outcome was assessed at least 1 year after surgery, according to Engel's modified classification. Patients with unilateral mesial temporal atrophy had significantly better results compared with the other two groups (p < 0.001): We found excellent results (class I or II outcome) in 93.6% of the patients with unilateral atrophy, in 61.7% of those with bilateral atrophy, and in 50% of the group with no significant atrophy of mesial temporal structures. The two different surgical techniques were equally effective, regardless of the pattern of atrophy. In conclusion, magnetic resonance volumetric studies in temporal lobe epilepsy proved to be an important preoperative prognostic tool for surgical treatment, but they did not provide guidance for selecting one surgical approach compared to the other.


Effects of osmotic pressure, glucose, and temperature on neurons in preoptic tissue slices.
The preoptic area contains thermosensitive, osmosensitive, and glucosensitive neurons, which have been implicated in thermal, osmotic, and metabolite regulations, respectively. In this study, rat preoptic tissue slices are used to examine the specificity of these neurons by determining their individual firing rate responses to thermal, osmotic, and glucose stimuli. Of the neurons classified according to thermosensitivity, 35% were warm sensitive, 10% were cold sensitive, and 55% were temperature insensitive. Of these, 107 neurons were also tested for their responses to tissue slice perfusions of low-glucose and/or hyperosmotic media. These experimental perfusions affected one-third of the temperature-insensitive neurons and nearly half of the thermosensitive neurons and generally excited warm-sensitive neurons and inhibited cold-sensitive neurons. A lack of specificity was also observed between the groups of osmosensitive and glucosensitive neurons, since most of the responsive neurons were affected by both hyperosmotic and low-glucose media. Although these findings do not suggest a strong functional specificity for preoptic neurons, they do support previous studies that emphasize interactions between regulatory systems.


[Forest resources in Qungyuan County of Liaoning, Northeast China: the structure and optimal spatial allocation].
By using RS/GIS techniques and the method of multiple objective grey situation decision, and in considering the forest economic benefits (biomass and stand productivity) and ecological benefits (water and soil conservation) , an optimal spatial allocation of the present forest types in Qingyuan County of Liaoning, Northeast China was approached in this study. After the optimization of spatial allocation, the structural proportions of different forest types in Qingyuan County changed obviously, with the area of coniferous forests reduced from 43% to 23% , the area of broadleaved forests reduced from 51% to 31% , the area of mixed coniferous-broadleaf forests increased from 3% to 43% , and the area of shrubs remained unchanged. As compared with the results before optimization, the biomass, stand productivity, and water conservation function of the forest ecosystem in Qingyuan County after optimization increased by 0.6%, 2.1% , and 31.7%, respectively, and the soil conservation function remained unchanged. It could be concluded that after the optimization of spatial allocation, the forest ecosystem of Qingyuan County could maintain its soil conservation function, and, at the time of keeping higher timber production, fully exert waler conservation function, realizing the maximization of the economic and ecological benefits of the forest ecosystem.


The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans.
Ghrelin is a novel growth hormone-releasing peptide, originally identified in the rat stomach as the endogenous ligand for the growth hormone secretagogue-receptor (GHS-R1a). Ghrelin is involved in the regulation of GH release, but it has recently been suggested that ghrelin may have other actions, including effects on appetite, carbohydrate metabolism, heart, kidney, pancreas, gonads, and cell proliferation. The distribution of ghrelin, its functional receptor (type 1a) and the unspliced, non-functional GHS-R type 1b mRNA expression was investigated in various human tissues using classical and real-time reverse transcription and polymerase chain reaction. GHS-R1a was predominantly expressed in the pituitary and at much lower levels in the thyroid gland, pancreas, spleen, myocardium and adrenal gland. In contrast, ghrelin was found in the stomach, other parts of the gut and, indeed, in all the tissues studied (adrenal gland, atrium, breast, buccal mucosa, esophagus, Fallopian tube, fat tissue, gall bladder, human lymphocytes, ileum, kidney, left colon, liver, lung, lymph node, muscle, muscle, myocardium, ovary, pancreas, pituitary, placenta, prostate, right colon, skin, spleen, testis, thyroid, and vein). GHS-R1b expression was also widespread in all tissues studied. The significance of the widespread tissue distribution of ghrelin remains to be determined. These data suggest that ghrelin might have widespread physiological effects via different, partly unidentified, subtypes of the GHS-R in endocrine and non-endocrine tissues.


Immunolocalization of multispecific organic anion transporters, OAT1, OAT2, and OAT3, in rat kidney.
Recently, a family of multispecific organic anion transporters has been identified, and several isoforms have been reported. However, the physiologic and pharmacologic roles of each isoform, except OAT1, in the transepithelial transport of organic anions in the kidney remain to be elucidated. To address this issue, it is essential to determine the intrarenal distribution and membrane localization of each OAT isoform along the nephron. In this study, the intrarenal distributions of rOAT1, rOAT2, and rOAT3 were investigated by an immunofluorescence method that used frozen rat serial kidney sections. Confocal microscopic analysis showed that immunoreactivity for rOAT1 was detected exclusively in the proximal tubules (S1, S2, S3) in the cortex with basolateral membrane staining. rOAT2 was detected in the apical surface of the tubules in the medullary thick ascending limb of Henle's loop (MTAL) and cortical and medullary collecting ducts (CD). rOAT3 was localized in the basolateral digitation of the cell membrane in all the segments (S1, S2, and S3) of the proximal tubules, MTAL, cortical TAL, connecting tubules, and cortical and medullary CD. These results on the distribution of each OAT isoform will facilitate the understanding of the role of OATs in the renal processing of organic anions.


[Bariatric surgery in children and adolescents].
Obesity in childhood and adolescents has gained epidemic proportions; in Germany 15-20 % of boys and girls are overweight, more than 6 % are known to be obese. By now, 25 % of relevant people show a pathological glucose intolerance, 4-5 % are developing type 2 diabetes mellitus (T2DM). In addition, metabolic disorders leading to hypertension and cardiac, renal or ophthalmological complications could be named as serious comorbidities. Medical and behavioural intervention as treatment for obesity in childhood remains largely ineffective: 5-10 % weight loss within 2 years rarely results in significant durable success. In adults, bariatric surgery is being used increasingly as an effective approach to achieve weight loss and to improve serious medical comorbidities, in particular T2DM. Enhancement of quality of life and explicit extension of survival are concomitant phenomenons. To date, a range of different types of bariatric procedures has been performed in adolescents, but studies evaluating and analysing preoperative data, postoperative course and follow-up in a representative number of patients younger than 18 years are still lacking. Nevertheless, current experience suggests significant weight loss and improving obesity-related medical comorbidities after bariatric surgery in adolescents too. Moreover, bariatric surgery in adolescents seems to induce less complications and a shorter hospital stay than in adults. Al-though surgical therapy for obesity in this group of patients remains an individual decision, even though explicit guidelines have been published specifying inclusion and exclusion criterias. Analysis of our own patient group and results of the study of the quality assurance "surgical treatment of morbid obesity" are appropriate tools to evaluate surgical techniques and to provide long-term follow-up.


[I.v. famotidine versus i.v. ranitidine: intragastric pH behavior in surgical intensive care patients].
20 patients of a surgical intensive care unit were treated in a randomised double-blind fashion with i.v. famotidine 10 mg and i.v. ranitidine every 6-12 hours for maximally seven days. Both groups were comparable with respect to the grade of risk of stress-induced bleeding. With both H2-blockers (ranitidine and famotidine) the intragastric pH could be increased to 5.0 and more and kept constant at this level over the whole test period. The mean daily doses required were 22.3 mg for famotidine and 154.3 mg for ranitidine. Stress-induced bleeding as well as adverse reactions could not be observed in both treatment groups.


Unveiling the hidden structure of complex stochastic biochemical networks.
Complex Markov models are widely used and powerful predictive tools to analyze stochastic biochemical processes. However, when the network of states is unknown, it is necessary to extract information from the data to partially build the network and estimate the values of the rates. The short-time behavior of the first-passage time distributions between two states in linear chains has been shown recently to behave as a power of time with an exponent equal to the number of intermediate states. For a general Markov model we derive the complete Taylor expansion of the first-passage time distribution between two arbitrary states. By combining algebraic methods and graph theory approaches it is shown that the first term of the Taylor expansion is determined by the shortest path from the initial state to the final state. When this path is unique, we prove that the coefficient of the first term can be written in terms of the product of the transition rates along the path. It is argued that the application of our results to first-return times may be used to estimate the dependence of rates on external parameters in experimentally measured time distributions.


Improving Fecal Immunochemical Testing Rates for Colon Cancer Screening in the Outpatient Setting.
The amount of colorectal cancer (CRC) screening using the noninvasive fecal immunochemical test (FIT) at a federally qualified health center, Five Rivers Health Clinic (Dayton, Ohio), has been low historically. Our quality improvement (QI) project aimed to improve CRC screening adherence in eligible patients who opted for FIT. Three hundred ninety-two patients with FIT orders for CRC were screened during an 11-month period. The preintervention group (pre-I) was enrolled from December 1, 2018 to May 31, 2019, and the postintervention group (post-I) from June 1, 2019 to October 31, 2019. Three interventions were used: resident physicians trained during clinic meetings regarding FIT education for patients, posters displayed in patient rooms outlining the benefits of CRC screening, and standardized US mail reminder letters sent to FIT patients. Patient demographics and clinical variables were collected along with return rate. The return rate for post-I was twice that of pre-I (74.4%, 95% confidence interval 64.6-82.3 vs 31.1, 95% confidence interval 26.2-36.6; P < 0.001). The pre-I/post-I groups did not differ on demographic and clinical characteristics, and, except for race, none of these variables was associated with returning the FIT screening card. The compliance rate for FIT completion and return more than doubled among our clinic patients after using a three-component QI intervention. Except for a difference in race, the lack of association between demographic and clinical characteristics with either pre-I/post-I group or return/no return of the FIT card leads us to conclude that our QI program for increasing FIT compliance is effective. Other settings where CRC screening is a prominent component of preventive care may benefit from adopting a similar QI intervention.


Peripheral nerve amyloidosis in sural nerve biopsies: a clinicopathologic analysis of 13 cases.
Amyloidosis is a well-recognized but uncommon cause of peripheral neuropathy. Our objectives were to determine the overall prevalence of peripheral nerve amyloidosis in sural nerve biopsies and to evaluate the clinical and pathologic features of these lesions. All available histologic and ultrastructural materials on biopsy tissue from 13 cases of peripheral nerve amyloidosis were examined. Muscle biopsies performed at the same time as the nerve biopsy were reviewed when available. Clinical data were collected on all patients. The prevalence of amyloidosis in sural nerve biopsies at our institution was 13 (1.2%) of 1098 cases over a 15.8-year period. These patients ranged in age from 41 to 82 years (median, 61 years) at initial presentation and included 10 men and 3 women. Presenting neuropathy symptoms were sensory in 6 of the 13 patients, motor in 2 cases, and mixed in 5 cases. Cardiac, renal, or gastrointestinal involvement was present in 7 of 13 cases. Two patients had myeloma and 7 had systemic autonomic symptoms. Two patients had probable familial amyloid polyneuropathy, and 1 patient demonstrated an alanine 60 point mutation. Amyloid, identified as amorphous eosinophilic extracellular deposits demonstrating apple green birefringence on Congo red stain or recognized by its characteristic fibrillar ultrastructure by electron microscopy, was identified in the endoneurium in 12 nerves, perineurium in 2 nerves, and epineurium in 9 nerves. Chronic inflammation was identified in 5 nerves. Axonal loss was recorded as mild (<25%) in 1 nerve, moderate (25% to 75%) in 8 nerves, and severe (>75%) in 4 nerves. Axonal degeneration predominated over demyelination in 8 of 10 cases that could be evaluated. Concomitant muscle biopsies contained amyloid deposits in 8 of 9 cases. Amyloidosis is a rare (1.2% in our series) cause of peripheral neuropathy with a distinct microscopic and ultrastructural appearance. Just over half the patients in our study had visceral organ involvement and systemic autonomic symptoms. The peripheral neuropathy was associated with axonal degeneration and a moderate to severe axonal loss in the majority of cases. Amyloid deposition was present in 8 out of 9 muscle biopsies performed at the same time.


Use of an antagonist of HMGB1 in mice affected by malignant mesothelioma: a preliminary ultrasound and optical imaging study.
Malignant mesothelioma (MM) is an aggressive tumor, with a poor prognosis, usually unresectable due to late diagnosis, mainly treated with chemotherapy. BoxA, a truncated form of "high mobility group box 1" (HMGB1), acting as an HMGB1 antagonist, might exert a defensive action against MM. We investigated the potential of BoxA for MM treatment using experimental 40-MHz ultrasound and optical imaging (OI) in a murine model. Murine MM cells infected with a lentiviral vector expressing the luciferase gene were injected into the peritoneum of 14 BALB/c mice (7 × 104 AB1-B/c-LUC cells). These mice were randomized to treatment with BoxA (n = 7) or phosphate-buffered saline (controls, n = 7). The experiment was repeated with 40 mice divided into two groups (n = 20 + 20) and treated as above to confirm the result and achieve greater statistical power. Tumor presence was investigated by experimental ultrasound and OI; suspected peritoneal masses underwent histopathology and immunohistochemistry examination. In the first experiment, none of the 7 controls survived beyond day 27, whereas 4/7 BoxA-treated mice (57.1%) survived up to day 70. In the second experiment, 6/20 controls (30.0%) and 16/20 BoxA-treated mice (80.0%) were still alive at day 34 (p = 0.004). In both experiments, histology confirmed the malignant nature of masses detected using experimental ultrasound and OI. In our preclinical experience on a murine model, BoxA seems to exert a protective role toward MM. Both experimental ultrasound and OI proved to be reliable techniques for detecting MM peritoneal masses.


Sudden unexpected deaths in epileptics--a literature review.
In summary, SUDEP accounts for death in approximately 8% of the young epileptic population. It is commoner in young male epileptics with a long history of generalised seizures, who have a history of head trauma and alcohol excess, and who are taking more than one antiepileptic drug. Most deaths are unwitnessed and occur at home, usually in bed and presumably overnight. Subtherapeutic AED levels do not necessarily imply non compliance, and may simply reflect drug degradation in the plasma after death. Many victims have pulmonary oedema on postmortem examination, and some show ischaemic damage of the heart despite normal coronary arteries. This possibly arises as a result of repeated episodes of vasoconstriction from seizure related catecholamine bursts. Animal studies have demonstrated the occurrence of central apnoea and also support the theory of acute fatal cardiac failure. Possible association with the daily level of geomagnetic activity is reported. The precise reason for a particular seizure being fatal in an otherwise healthy individual is as yet undetermined.


An examination of consumer advisement warning information embedded within written instructions: implications for memory and behaviour.
The effects of the colour and placement of consumer advisement warning information embedded within written instructions on both memory for, and compliance with, information were examined. Specifically, undergraduate subjects were instructed to read a set of written instructions for operating a camera. Subjects read consumer advisement warning information typed in either red, blue, or black ink, which was located at either the top, middle, or bottom of the written instructions. After reading the instructions, subjects were asked to take pictures using the camera. Compliance with the information and subsequent memory for the information were assessed. Results indicated that for memory there was an interaction between colour and placement, and for behaviour there was a main effect of placement. The implications of this interaction for memory of consumer advisements is discussed. In addition, the possible role of perceived importance of the advisement information in the prediction of memory and behaviour is considered.


Hydrodynamic narrowing of tubes extruded from cells.
We discuss the pulling force f required to extrude a lipid tube from a living cell as a function of the extrusion velocity L. The main feature is membrane friction on the cytoskeleton. As recently observed for neutrophils, the tether force exhibits a "shear thinning" response over a large range of pulling velocities, which was previously interpreted by assuming viscoelastic flows of the sliding membrane. Here, we propose an alternative explanation based on purely Newtonian flow: The diameter of the tether decreases concomitantly with the increase of the membrane tension in the lipid tube. The pulling force is found to vary as L(1/3), which is consistent with reported experimental data for various types of cells.


On-line comprehensive two dimensional separations of charged compounds using reversed-phase high performance liquid chromatography and hydrophilic interaction chromatography. Part II: application to the separation of peptides.
In this second paper of a two-part series, on-line RPLC×HILIC is compared to on-line RPLC×RPLC through the separation of peptides. Our choices regarding the conditions are discussed. Injection effects and overloading effects are evaluated in both configurations. It is shown that whereas large volumes can be injected in the second dimension in RPLC×RPLC under HT-UHPLC conditions (>20% of the column dead volume), even small injection volumes (8% of the column the dead volume) have a detrimental effect on peak shapes in RPLC×HILIC. Advantages and limits of the two 2D-systems are compared through the 2D-separation of a tryptic digest of three proteins. A ten-fold gain in analysis time along with a significant gain in peak capacity are obtained with both systems compared to the most efficient one-dimensional separation of peptides recently published.


Novel use of idebenone in Leber's hereditary optic neuropathy in Hong Kong.
We report a case of a young Chinese male presenting with sequential, painless, bilateral visual loss in Hong Kong. He was diagnosed to have Leber's hereditary optic neuropathy with genetic workup showing G11778A mutation with over 80% heteroplasmy. He was started on idebenone treatment 11 months after onset of the binocular disease. To our best knowledge, this is the first case of Leber's hereditary optic neuropathy treated with idebenone in Hong Kong. The recent evidence of the diagnosis and treatment of this devastating disease is reviewed.


Isolation and enzymatic characterization of lamjapin, the first ribosome-inactivating protein from cryptogamic algal plant (Laminaria japonica A).
Lamjapin, a novel type Iota ribosome-inactivating protein, has been isolated from kelp (Laminaria japonica A), a marine alga. This protein has been extensively purified through multiple chromatography columns. With a molecular mass of approximately 36 kDa, lamjapin is slightly larger than the other known single-chain ribosome-inactivating proteins from the higher plants. Lamjapin can inhibit protein synthesis in rabbit reticulocyte lysate with an IC50 of 0.69 nm. It can depurinate at multiple sites of RNA in rat ribosome and produce the diagnostic R-fragment and three additional larger fragments after the aniline reaction. Lamjapin can deadenylate specifically at the site A20 of the synthetic oligoribonucleotide (35-mer) substrate that mimics the sarcin/ricin domain (SRD) of rat ribosomal 28S RNA. However, it cannot hydrolyze the N-C glycosidic bond of guanosine, cytidine or uridine at the corresponding site of the A20 of three mutant SRD RNAs. Lamjapin exhibits the same base and position requirement as the ribosome-inactivating proteins from higher plants. We conclude that lamjapin is an RNA N-glycosidase that belongs to the ribosome-inactivating protein family. This study reports for the first time that ribosome-inactivating protein exists in the lower cryptogamic algal plant.


[Changes in levels of acute phase proteins in patients with central hypercortisolism].
Acute phase protein reaction depends on complex interaction of proinflammatory cytokines and hormones, especially glucocorticoids. Glucocorticoids are essential factors for hepatocellular microenvironment and proteosynthesis during both rest and inflammatory period. Cushing's disease represents a model of glucocorticoid hyperstimulation of acute phase protein synthesis without interleukin-6 and other cytokine influence. 20 patients (age of 38 +/- 11, 11 males, 9 females) with a diagnosis of central hypercorticolism were examined. Plasma levels of 11 acute phase proteins were estimated. These results were compared with plasma ACTH, interleukin-6, and U-cortisol concentrations and correlated to the control group (healthy volunteers, age 30 +/- 5, 13 males, 7 females). Plasma levels of albumin and prealbumin in patients with Cusing's disease were significantly lower. We proved significant elevation of alpha 1-acid glycoprotein, haemopexin, and fibrinogen compared with healthy subjects. The positive correlation of alpha 1-acid glycoprotein and U-cortisol (r = 0.51, p < 0.01), haemopexin and U-cortisol (r = 0.47, p < 0.05) respectively was found. The interaction between glucocorticoids and proinflammatory cytokines in acute phase protein synthesis depends on permissive effects of corticoids on cytokine signal transduction in hepatocytes. However, our results document that corticoida themselves significantly stimulate acute phase protein synthesis, and this stimulation differs from inflammatory pattern of hepatic proteosynthesis.


Ballistocardiography and seismocardiography: a review of recent advances.
In the past decade, there has been a resurgence in the field of unobtrusive cardiomechanical assessment, through advancing methods for measuring and interpreting ballistocardiogram (BCG) and seismocardiogram (SCG) signals. Novel instrumentation solutions have enabled BCG and SCG measurement outside of clinical settings, in the home, in the field, and even in microgravity. Customized signal processing algorithms have led to reduced measurement noise, clinically relevant feature extraction, and signal modeling. Finally, human subjects physiology studies have been conducted using these novel instruments and signal processing tools with promising results. This paper reviews the recent advances in these areas of modern BCG and SCG research.


KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma.
Despite curative-intent treatment, most patients with locally advanced esophageal cancer will experience disease recurrence or locoregional progression, highlighting the need for new therapies. Current guidelines recommend definitive chemoradiotherapy in patients ineligible for surgical resection, but survival outcomes are poor. Pembrolizumab is well tolerated and provides promising antitumor activity in patients with previously treated, advanced, unresectable esophageal/esophagogastric junction cancer. Combining pembrolizumab with chemoradiotherapy may further improve outcomes in the first-line setting. Here, we describe the design and rationale for the double-blind, Phase III, placebo-controlled, randomized KEYNOTE-975 trial investigating pembrolizumab in combination with definitive chemoradiotherapy as first-line treatment in patients with locally advanced, unresectable esophageal/gastroesophageal junction cancer. Overall survival and event-free survival are the dual primary end points. Clinical trial registration: NCT04210115 (ClinicalTrials.gov).


Epidermal growth factor receptor tyrosine kinase inhibitors for elderly patients with advanced non-small cell lung cancer.
Lung cancer is the leading cause of cancer-related mortality in both men and women and approximately 219,440 new cases of nonsmall cell lung cancer (NSCLC) were estimated to occur in the USA in 2009, which caused 159,390 NSCLC-related deaths. More than 50% of cases of advanced NSCLC are diagnosed in patients older than age 65, and recent Surveillance Epidemiology and End Results (SEERs) data suggest that the median age at diagnosis is 70 years. Until recently, the disease has been undertreated in this patient population, with a perception among many clinicians that elderly patients do not tolerate chemotherapy or radiotherapy. So, single agent chemotherapy is the recommended approach by the ASCO and International Expert Panels in unselected patients. The introduction of novel targeted therapies, such as Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) which improved survival versus placebo in patients who had previously failed on chemotherapy, gives clinicians new, effective, and better tolerated options to consider when treating NSCLC in elderly patients. This paper describes the advances of EGFR TKIs for elderly patients with advanced NSCLC.


[Experimental study of the optimization of the hip endoprosthesis].
Clinical and laboratory investigations have resulted in a new design for the shaft prosthesis of the "St. Georg" model total hip prosthesis, the purpose of which was to minmize the risk of biomechanical complications. The original method of attachment and the same material for the limb were retained for our investigations. It was possible to test the bending strength, the length, and the geometry of the shaft as well as how structure of the bearing surface of the collar influences the force flow within the compound system. The distrubances produced in physiological force flow produced on insertion were also investigated. The results obtained enabled us to design a new shaft prosthesis.


Mesothelial cyst of the round ligament misdiagnosed as irreducible inguinal hernia.
We report the case of a 36-year-old woman who presented with signs and symptoms of an irreducible inguinal hernia. Surgical exploration revealed a mesothelial cyst of the round ligament of the uterus. Mesothelial cysts of the round ligament are rare lesions, frequently masquerading as inguinal hernias, and should be included in the differential diagnosis of any inguinal mass. Clinical findings are those of a groin mass, discomfort, and bulging. Ultrasound and CT scans often demonstrate an aperistaltic cystic mass. Definitive diagnosis is usually made intraoperatively and confirmed histopathologically.


Experimental infection of chickens with Salmonella enteritidis.
Following oral inoculation of newly hatched commercial broilers, four phage types of Salmonella enteritidis showed considerable variation in their virulence. The percentage mortality varied from 96%, produced by a phage type 4 strain, to 20% (phage type 13a). When high mortality was observed, chickens that died showed a polyserositis with pericarditis similar to that observed in naturally occurring cases. Strains of phage types 4, 6 and 8 were more virulent than a phage type 13a strain when inoculated by the intramuscular route. Similar variations in virulence were observed in newly hatched Rhode Island Red chickens although the overall mortality observed was much reduced. Polyserositis was again observed. Despite similarly high viable numbers of all the phage types being present in the caecal contents, the strains of phage types 4 and 6 were isolated from the spleen at 12 h post-inoculation whereas phage types 8 and 13a were not. After 24 h the viable counts of phage type 4 in the spleen were ten times higher than those of type 13a. However, it is unclear whether this is the result of enhanced invasiveness only or whether an increased ability to multiply in the spleen is also involved. All strains were very invasive in cultured Vero cells; phage type 4 strains slightly more so than types 6, 8 and 13a. Strains of phage type 4 and 13a persisted in the faeces of chickens placed in-contact with orally inoculated birds longer than did strains of types 6 or 8.


The effect of bone marrow mesenchymal stem cells on highly metastatic MHCC97-H hepatocellular carcinoma cells following OPN and TGFβ1 gene silencing.
The metastatic behavior of hepatocellular carcinoma (HCC) is one of the key factors that leads to poor prognosis. The aim of the current study was to determine the changes in metastasis and the proliferation potential of bone marrow mesenchymal stem cells (BMSCs) in high metastatic potential hepatocellular carcinoma (MHCC97-H) following gene silencing. The osteopontin (OPN) and transforming growth factor-β (TGFβ1 ) genes, which are associated with metastasis and tumor proliferation, were silenced in MHCC97-H cells. Transwell assays were used to evaluate the migration of MHCC97-H cells in vitro. Additionally, a murine model of MHCC97-H lung metastasis was established. Following OPN and TGFβ1 silencing, the migration of MHCC97-H cells was significantly reduced following BMSC intervention (P<0.01). Furthermore, there were few MHCC97-H cells in the lung tissues of the OPN- and TGFβ1 -silenced animals, and their integrated optical density (IOD) value was significantly lower compared with controls (P<0.05). Immunofluorescence of lung metastasis in the MHCC97-H model revealed that there was no significant difference in the IOD value of integrin αvβ3 expression in the OPN- and TGFβ1 -silenced groups compared with controls (P>0.05). The metastasis and proliferation potential of MHCC97-H following BMSC intervention were significantly reduced in vitro and in vivo, especially in the TGFβ1-silenced group. The decrease in the metastatic potential in gene-silenced MHCC97-H cells was not associated with integrin αvβ3 expression. Therefore, OPN and TGFβ1 may be potential targets for HCC treatment, and TGFβ1 may have a higher therapeutic potential for BMSC intervention.


Feruloylputrescine and Caffeoylputrescine Are Not Involved in Growth and Floral Bud Formation of Stem Explants from Nicotiana tabacum L. var Xanthi nc.
The role of feruloylputrescine (FP) and of caffeoylputrescine (CP) was investigated in an explant system of stem explants from day-neutral Nicotiana tabacum L. var Xanthi nc. Previously, a correlation between cortical callus formation and increase in FP content, as well as between in vitro flower formation and increase in CP content had been shown. During the explant growth in vitro, the increase of both FP and CP was inhibited by 4-fluor-(1-amino-2-phenylethyl)phosphonic acid and 2-amino-indene-2-phosphonic acid, both inhibitors of phenylalanine ammonia-lyase (EC 126.96.36.199). dl-alpha-difluoromethylarginine, an inhibitor of arginine decarboxylase (ADC, EC 188.8.131.52), prevented only the increase in FP, while dl-alpha-difluoromethylornithine, an inhibitor of ornithine decarboxylase (EC 184.108.40.206), reduced only that of CP. Increase in dry weight and the formation of cortical callus and of floral buds of explants were not affected by any of the inhibitors. We conclude, in contrast to earlier hypotheses, that FP and CP do not trigger growth and differentiation in the explants. It seems more likely that FP and CP increase in response to auxin and cytokinin in the media.


[Health as an interdisciplinary construction. Example of the dialogue between geography, health and territory].
It is common to confuse health and medicine, but this comparison is far too limited to promote health. Health is related to the living conditions of the individual, from all points of view: food, education, housing, work, travels, health care. Obviously the latter is part of it but is just one link in a long chain. A health condition is the result of a system of multiple interactive components at a given time and in a given place: endogenous factors (physical, biological, genetic) and exogenous ones (political, economic, social and cultural environments, features of the living conditions). The discrepancies are the results of the differentiated combinations of these factors. Some contexts associate a series of health protecting factors whereas others associate factors of vulnerability. There has always been a dialogue between, on the one hand, medicine and, on the other hand, sociology, anthropology and economy. It dates back to antiquity for geography (cf: Hippocrates treatise: on air, water and places) but it disappeared at the time of Pasteur revolution. The 20th century marks the return of geography and in 2009 a French law takes hold of one of its key words "territory". Why? What are the contributions of this discipline? Maps are a strong image of this discipline, which cannot be limited to this production. Geography also contributes to the laws of distance, polarity and flows and to the notions of scale, accessibility, network, basin, space for living, territorial dynamics.... We have here a very good opportunity to establish a dialogue between health and geography. Indeed, the perception of the territorial dimension of health issues is being reinforced both through the reading of epidemics such as SARS and flues and through the discrepancies in the health conditions. This reinforcement is related to the territorialization procedures. In the field of health care planning this discipline provides us, thanks to its tools, with decision-making diagnoses necessary for the promotion of a greater territorial equity. At the time of the implementation of the HPST (Law on Hospital - Patient - Health - Territory) and ARS (Regional Agency for Health) laws and of the debates on the health territories, the emphasis will be put on the French health care system.


Reactions to other corticosteroids in patients with positive patch test reactions to budesonide.
Corticosteroid cross-reactions have been classified into four well-defined groups. A previous study of patch test reactions to other corticosteroids in patients allergic to hydrocortisone failed to conform to these groups. It was suggested that substitution at the C6 and C9 positions of the corticosteroid was the most important determinant of a further reaction. Our aim was to analyze multiple positive patch tests to corticosteroids in patients sensitized to budesonide to confirm our earlier findings. Forty-six patients with positive patch tests to budesonide were patch-tested to 17 other topical corticosteroids. The results were examined by a generalized linear model and a chi-square test. Substitution of the corticosteroid at the C6 and C9 positions significantly reduced the number of reactions. A different substitution at the C16 and C17 positions was less important, and that at the C21 position was of no significance. Patients sensitized to budesonide are most likely to react to other non-C6 and non-C9 substituted corticosteroids.


Clinical Outcomes of Drug-Eluting Bead Transarterial Chemoembolization Loaded with Raltitrexed for the Treatment of Unresectable or Recurrent Hepatocellular Carcinoma.
Although raltitrexed shows therapeutic effects in many types of malignant tumors, the therapeutic effects and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) loaded with raltitrexed for the treatment of hepatocellular carcinoma (HCC) are rare. This study aimed to investigate the safety and efficacy of DEB-TACE with raltitrexed-loaded CalliSpheres beads (CB) in patients with unresectable or recurrent HCC. Between May 2018 and October 2021, 41 patients with unresectable or recurrent HCC treated by DEB-TACE loaded with raltitrexed were retrospectively enrolled. The primary end points were overall survival and progression-free survival. The response evaluation criteria in solid tumors (RECIST) criteria and modified RECIST criteria (mRECIST) were used to assess the tumor response after the DEB-TACE procedure. A total of 79 DEB-TACE procedures were successfully performed, and the technical success rate was 100%. The overall response rate and disease control rate assessed by mRECIST criteria were 76.9% and 88.5%, 62.5% and 70.8%, and 35.3% and 47.1%, respectively, at 1, 3, and 6 months postprocedure. The mean progression-free survival and overall survival were 21.6 ± 3.6 and 43.7 ± 5.8 months, respectively. The 6-, 24-, and 36-month overall survival rates were 86.8%, 62.7%, and 57.1%, respectively. Minor complications were observed in 21 patients (51.2%), with no treatment-related mortality or severe adverse events. The most common treatment-related complications were abdominal pain (48.8%) and nausea (29.3%). DEB-TACE with raltitrexed-loaded CB suggests a feasible, safe, and efficacious palliative regimen in unresectable or recurrent HCC patients.


[Integration in the workforce of Québec of adults living with Autism Spectrum Disorder or Asperger Syndrome].
This article presents an exploratory study evaluating the impact of the program Employment Pact: Québec in full force (2008) aimed at the integration in the workforce of adults living with Autism Spectrum Disorder (ASD) or Asperger Syndrome (AS). This program is implemented in different regions in Québec. The evaluation takes into consideration working conditions, integration procedures, as well as receptivity of eventual employers. Results demonstrate that the working conditions for these individuals are relatively similar, however, the type and number of services offered, as well as the training of service agents vary from one centre to another.


Ceropegia jinshaensis (Apocynaceae), a new species from northwestern Yunnan, China.
Ceropegia jinshaensis D.T.Liu & Z.K.Wu (Asclepiadoideae, Apocynaceae), a new species from northwestern Yunnan along the upper Yangtze river of China, is described and illustrated. This species is similar to C. meleagris H. Huber, C. dorjei C. E. C. Fischer and C. aridicola W. W. Smith, but can be distinguished easily by its leaf shape and floral features, especially the corolla shape and size, the interior of corolla tube and coronal characters.


Compounded Melatonin Cream for the Prevention and Treatment of Radiation Dermatitis: A Case Report.
Radiation-induced dermatitis is a common complication of radiotherapy. In Spain, the manufactured products used to prevent and treat that condition consist of emollient creams (which are often ineffective) or corticosteroids (which can cause dermal atrophy and other adverse effects). However, we have found that topically applied melatonin, a product that to our knowledge is not commercially available in Spain, is safe and effective in the prevention and treatment of radiodermatitis and a viable substitute for corticosteroid therapy. In this report, we describe the use of compounded melatonin in Beeler cream (the formulation for which is provided) in a 46-year-old woman who underwent surgery and radiotherapy for early stage adenocarcinoma of the breast. The patient applied that cream as directed throughout the prescribed course of radiotherapy and continued its use for 3 weeks after she last underwent irradiation. She experienced no adverse effects from the use of the compounded formulation and tolerated that treatment well. Radiation dermatitis did not develop at the irradiated site until approximately 1 week after the final radiotherapy session, at which time mild erythema of the treated skin emerged. That condition, which was successfully treated by application of the melatonin-containing cream as previously prescribed, resolved after 3 weeks of its use. We suggest that when manufactured products designed to prevent or treat the adverse dermal effects of radiotherapy are unavailable, fail to be effective, or prove objectionable to patients, a melatonin-containing topical compound can provide a successful alternative.


TAC-101, a novel retinobenzoic-acid derivative, enhances gap junctional intercellular communication among renal epithelial cells treated with renal carcinogens.
[4-3,5-Bis(trimethylsilyl)benzamido] benzoic acido] (TAC-101), which exhibits an anti-tumor effect, can bind to retinoic acid receptors (RARs). It has retinoid-like properties, such as chemopreventive action against cancer cells. The up-regulation of connexin (Cx) expression by retinoids is well known in various epithelial cells. In this study, we investigated whether TAC-101 up-regulates gap junctional intercellular communication (GJIC) in renal epithelial cells exposed to the renal carcinogens. Madin Darby canine kidney (MDCK) cells were incubated with TAC-101 for 3 days, then briefly exposed to renal carcinogens potassium bromate (KBrO3) or dimethylnitrosamine (DMN). TAC-101 increased the expression of connexin 43 protein without affecting Cx43 phosphorylation and prevented inadequate Cx43 localisation caused by KBrO3 or DMN. Consequently, TAC-101 prevented the disruption of GJIC in MDCK cells. These data suggested that TAC-101 enhanced GJIC by up-regulating Cx43 expression and that TAC-101 might be useful for the prevention of renal cell carcinoma.


Comment on 'Health aspects of cannabis: revisited' (Hollister).
Twelve years ago Leo Hollister (1986) published a review on health aspects of cannabis which can truly be called a 'classic'. In a field where emotions, prejudices and personal preferences frequently supplant objectivity, Hollister drew a picture not only solidly based on clinical studies - some of which came from his laboratory - but also on his thorough knowledge of drug dependence and medicine and on his common sense. For over a decade, at meetings, 'Hollister says' meant his 1986 review. He has now revisited the field, again demonstrating his mastery of the topic. In the 1986 review a portion was devoted to therapeutic uses. This aspect has not been revisited now, which we can only regret. I certainly would have liked to hear what he has to say on the debate on 'medical marijuana', on the clinical advantages of marijuana versus THC (or vice versa), and on specific issues such as the use of marijuana in multiple sclerosis, which is widely used by patients. Such a use is not supported in the US by the National Multiple Sclerosis Society, while in the UK, the British Medical Association strongly recommends 'carefully controlled trials of cannabinoids in patients with chronic spastic disorders which have not responded to other drugs'. Such trials merit a high priority (British Medical Association, 1997).


Vitamin D basis of Alzheimer's disease: from genetics to biomarkers.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder seen mostly in the elderly population. While to date AD research has focused on either neurochemical disruptions, genetic studies, or the pathological hallmarks, little has been done to establish a novel approach that would encompass all three aspects, one that would overcome the current barriers in AD research and determine the cause of AD and, eventually, discover a treatment. Meanwhile, there have been strong indications in recent years that vitamin D, a secosteroid hormone, and its receptors are fundamentally involved in neurodegenerative mechanisms. Observational studies have pointed to vitamin D deficiency as a genetic risk factor for AD, Parkinson's disease (PD), vascular dementia, and multiple sclerosis (MS), as well as other neurological disorders, brought about by alterations in genes involved in metabolism, transportation, and actions of vitamin D. Molecular studies have demonstrated that vitamin D treatments prevent amyloid production while also increasing its clearance from the brain in AD. Finally, recent vitamin D intervention studies have reported significant improvement in cognitive performance in subjects with senile dementia, mild cognitive impairment, and AD. This review aims to describe how a vitamin D research strategy, fully integrating all aspects of present-day AD research, would elucidate the genetic, molecular, and biochemical background of the disease.


Triterpenoids from Rubia yunnanensis.
Five new triterpenoids, rubiarbonones D (1), E (5), and F (2), and rubiarbosides F (3) and G (4), together with nine known compounds, were isolated from the roots of Rubia yunnanensis. The structures of 1-12 were elucidated by spectroscopic methods. The antiplatelet aggregation activities of rubiarbonone A (6) and rubiarbonol A (8) and B (9) were investigated with a standard protocol.


Leukocytoclastic Vasculitis as a Rare Manifestation of Staphylococcal Osteomyelitis.
Leukocytoclastic vasculitis (LCV), also known as small-vessel cutaneous vasculitis, is rarely seen in the setting of staphylococcal infection without bacteremia. Here, we present a case of LCV in a 61-year-old male with chronic staphylococcal osteomyelitis without any evidence of bacteremia. The rash resolved with the treatment of osteomyelitis. As seen in this case, local infection should be considered in the differential diagnosis of LCV even when there is no evidence of bacteremia.