Development and evaluation of a high-fidelity rhinoplasty simulator.
Rhinoplasty is a challenging procedure with a steep learning curve. Surgical simulators provide a safe platform to gain hands-on experience without compromising patient outcomes. Therefore, rhinoplasty is an ideal procedure to benefit from an effective surgical simulator. A high fidelity rhinoplasty simulator was developed using three-dimensional (3D) computer modelling, 3D printing and polymer techniques. The simulator was tested by six surgeons with experience in rhinoplasty to assess realism, anatomic accuracy, and value as a training tool. The surgeons performed common rhinoplasty techniques and were provided a Likert-type questionnaire assessing the anatomical features of the simulator. A variety of surgical techniques were successfully performed using the simulator including open and closed approaches. Bony techniques performed included endo-nasal osteotomies and rasping. Submucous resection with harvest of septal cartilage, cephalic trim, tip suturing as well as grafting techniques including alar rim, columellar strut, spreader and shield grafts were successfully performed. Overall, there was agreement in the simulator's anatomic accuracy of bony and soft tissue features. There was strong agreement in the simulator's overall realism and value as a training tool. The simulator provides a high-fidelity, comprehensive training platform to learn rhinoplasty techniques to augment real operating experience without compromising patient outcomes.


Effects of amnio-allantoic fluid exchange on bowel contractility in chick embryos with gastroschisis.
Intestinal damage in patients with gastroschisis is characterized by bowel wall thickening, intestinal dilatation, mesenteric shortening, and a fibrous peel. The prevention of intestinal damage in gastroschisis by amnio-allantoic fluid (AAF) exchange has been reported using histologic and macroscopic evaluation of intestines, but the effects of this treatment on bowel contractility have not been investigated. The current study was performed to determine the effect of AAF exchange on the intestinal contractility in chick embryos with gastroschisis. Thirteen-day-old fertilized chick eggs were used. Gastroschisis was created through amnio-allantoic cavity. There were 3 study groups: control group, gastroschisis-only group, and gastroschisis-plus-exchange group. The bowels were evaluated by an in vitro muscle strip technique, and the response was expressed as a percentage of the maximum acetylcholine evoked contraction (E(max)) in each tissue obtained. Additionally, parasympathetic ganglion cells per 10 plexus at the intestinal wall were counted. Differences between groups were analyzed by analysis of variance (ANOVA) followed by Tukey-Kramer. Probabilities of less than 5% were considered significant. The intestines were thickened and covered by fibrous peel in the gastroschisis-only group when compared with the control group and the gastroschisis exchange group morphologically. There was a statistically significant decrease in contractility in the gastroschisis-only group compared with the control group (P <.05). It exerted 42.03 +/- 46.73% contraction of control group's E(max). This decrease in contractility was significantly reversed in the exchange group (P <.05; E(max) value of gastroschisis plus exchange group was 71.45 +/- 23.54% of control group's E(max)). Although the number of ganglia per 10 plexus was 76.7 +/- 4.3 in the control group, it was measured 28% less in the gastroschisis-only group (P <.05). There was no significant difference between the ganglion numbers of control and exchange groups. Prenatal AAF exchange treatment prevents decreased bowel contractility in gastroschisis. Gastroschisis does not affect intestinal ganglia morphology, but the number of ganglion cells decreases. AAF exchange prevents these functional and morphologic adverse effects of disease. By these findings the expectancy of a better clinical result in gastroschisis with intrauterine pretreatment by amniotic fluid exchange increases.


Immunomodulatory effects of dietary intake of chitin on gilthead seabream (Sparus aurata L.) innate immune system.
To determine the effects of chitin (poly [1-->4]-beta-N-acetyl-D-glucosamine) on the innate immune response of gilthead seabream (Sparus aurata L.), fish were fed diets containing 0 mg (control), 25, 50 or 100 mg kg(-1) chitin for 2, 4 and 6 weeks. Lysozyme and natural haemolytic complement activities, together with head-kidney leucocyte respiratory burst, phagocytic and cytotoxic activities, were studied at each of the assayed times. Lysozyme activity was unaffected by the administration of chitin. The innate humoral and cellular immune response activities assayed were enhanced by the dietary intake of chitin, each increasing at a different time: natural haemolytic complement activity and cytotoxic activity after 2 weeks of treatment, respiratory burst activity from 4 weeks and phagocytic activity after 6 weeks, although, unlike the other activities, no statistically significant differences were observed in the first. The results indicate that chitin increases the activity of the seabream innate immune system, and its use as an immunostimulant is discussed, especially with regards to the protective role.


The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve.
The distance between the two electrode tips can greatly influence the parameters used for recording compound nerve action potentials. To investigate the optimal parameters for these recordings in the rat median nerve, we dissociated the nerve using different methods and compound nerve action potentials were orthodromically or antidromically recorded with different electrode spacings. Compound nerve action potentials could be consistently recorded using a method in which the middle part of the median nerve was intact, with both ends dissociated from the surrounding fascia and a ground wire inserted into the muscle close to the intact part. When the distance between two stimulating electrode tips was increased, the threshold and supramaximal stimulating intensity of compound nerve action potentials were gradually decreased, but the amplitude was not changed significantly. When the distance between two recording electrode tips was increased, the amplitude was gradually increased, but the threshold and supramaximal stimulating intensity exhibited no significant change. Different distances between recording and stimulating sites did not produce significant effects on the aforementioned parameters. A distance of 5 mm between recording and stimulating electrodes and a distance of 10 mm between recording and stimulating sites were found to be optimal for compound nerve action potential recording in the rat median nerve. In addition, the orthodromic compound action potential, with a biphasic waveform that was more stable and displayed less interference (however also required a higher threshold and higher supramaximal stimulus), was found to be superior to the antidromic compound action potential.


Pulmonary embolism: predicting disease severity.
Pulmonary embolism (PE) is the most common cause of acute pulmonary hypertension, yet it is commonly undiagnosed, with risk of death if not recognized promptly and managed accordingly. Patients typically present with hypoxemia and hypomania, although the presentation varies greatly, being confounded by co-morbidities such as pre-existing cardio-respiratory disease. Previous studies have demonstrated variable patient outcomes in spite of similar extent and distribution of pulmonary vascular occlusion, but the path physiological determinants of outcome remain unclear. Computational models enable exact control over many of the compounding factors leading to functional outcomes and therefore provide a useful tool to understand and assess these mechanisms. We review the current state of pulmonary blood flow models. We present a pilot study within 10 patients presenting with acute PE, where patient-derived vascular occlusions are imposed onto an existing model of the pulmonary circulation enabling predictions of resultant haemodynamic after embolus occlusion. Results show that mechanical obstruction alone is not sufficient to cause pulmonary arterial hypertension, even when up to 65 per cent of lung tissue is occluded. Blood flow is found to preferentially redistribute to the gravitationally non-dependent regions. The presence of an additional downstream occlusion is found to significantly increase pressures.


The generation of pharyngeal phase of swallow and its coordination with breathing: interaction between the swallow and respiratory central pattern generators.
Swallowing and breathing utilize common muscles and an anatomical passage: the pharynx. The risk of aspiration of ingested material is minimized not only by the laryngeal adduction of the vocal folds and laryngeal elevation but also by the precise coordination of swallows with breathing. Namely, swallows: (1) are preferentially initiated in the postinspiratory/expiratory phase, (2) are accompanied by a brief apnea, and (3) are often followed by an expiration and delay of the next breath. This review summarizes the expiratory evidence on the brainstem regions comprising the central pattern generator (CPG) that produces the pharyngeal stage of swallow, how the motor acts of swallowing and breathing are coordinated, and lastly, brainstem regions where the swallowing and respiratory CPGs may interact in order to ensure "safe" swallows.


[The specificity of so-called "smoker cells" in lung tissue].
A simple test for demonstration of smoker cells was verified on bronchoalveolar lavage (BAL) and cytological smears of lung tissue. Alveolar macrophages exhibit in 81% (BAL) respectively 86% (surgical material) of the smokers with Fettrot 7B a red colouring of the cytoplasm. Only few non-smokers show a positive reaction for smoker cells. In ex-smokers this positive reaction disappears after 7 month. We conclude, that this method is very sensitive but not absolutely specific for detecting smokers with a simple cytological test.


Sandwich-Structured Implants to Obstruct Multipath Energy Supply and Trigger Self-Enhanced Hypoxia-Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis.
As a currently common strategy to treat cancer, surgical resection may cause tumor recurrence and metastasis due to residual postoperative tumors. Herein, an implantable sandwich-structured dual-drug depot is developed to trigger a self-intensified starvation therapy and hypoxia-induced chemotherapy sequentially. The two outer layers are 3D-printed using a calcium-crosslinked mixture ink containing soy protein isolate, polyvinyl alcohol, sodium alginate, and combretastatin A4 phosphate (CA4P). The inner layer is one patch of poly (lactic-co-glycolic acid)-based electrospun fibers loaded with tirapazamine (TPZ). The preferentially released CA4P destroys the preexisting blood vessels and prevents neovascularization, which obstructs the external energy supply to cancer cells but aggravates hypoxic condition. The subsequently released TPZ is bioreduced to cytotoxic benzotriazinyl under hypoxia, further damaging DNA, generating reactive oxygen species, disrupting mitochondria, and downregulating hypoxia-inducible factor 1α, vascular endothelial growth factor, and matrix metalloproteinase 9. Together these processes induce apoptosis, block the intracellular energy supply, counteract the disadvantage of CA4P in favoring intratumor angiogenesis, and suppress tumor metastasis. The in vivo and in vitro results and the transcriptome analysis demonstrate that the postsurgical adjuvant treatment with the dual-drug-loaded sandwich-like implants efficiently inhibits tumor recurrence and metastasis, showing great potential for clinical translation.


TNFAIP3-DEPTOR complex regulates inflammasome secretion through autophagy in ankylosing spondylitis monocytes.
Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease with severe inflammatory symptoms in the axial skeleton. The cause of ankylosing spondylitis is unknown. TNFAIP3, also named A20, uses ubiquitin-related functions to regulate immune activation, deficiency of which is highly related to autoimmune disease. However, the role of TNFAIP3 in human AS has not been reported. Our objective was to study the role and mechanism of TNFAIP3 in ankylosing spondylitis. TNFAIP3 expression on different types of immunocytes from AS peripheral blood was measured by flow cytometry. In vitro, monocytes were transfected with a TNFAIP3 shRNA lentivirus, and IL6 and IL1B activation was tested using real-time PCR and ELISA. The novel interaction complex TNFAIP3-DEPTOR was determined through GST pull-down, yeast two-hybrid system, confocal microscopy, and co-immunoprecipitation. Transmission electron microscopy, the RFP-GFP-LC3 adenovirus, and LC3 expression were used for autophagy detection. Here, we show that TNFAIP3 expression in AS peripheral blood non-classical monocytes was decreased. In normal monocytes, TNFAIP3 induced autophagy, which restricted inflammasome activation to the early stage of LPS stimulation. Zinc-finger domains of TNFAIP3 were able to interact and stabilize DEPTOR. TNFAIP3 and DEPTOR together rapidly promoted autophagy after LPS treatment to prevent NLRP3 inflammasome formation. Finally, TNFAIP3 and DEPTOR deficiency in AS non-classical monocytes facilitated inflammasome activation. Our study indicates that TNFAIP3-DEPTOR complex-induced early-onset autophagy is vital for immune inhibition in autoimmune disease.


Enhanced Antibacterial Activity of Repurposed Mitomycin C and Imipenem in Combination with the Lytic Phage vB_KpnM-VAC13 against Clinical Isolates of Klebsiella pneumoniae.
Klebsiella pneumoniae is an opportunistic Gram-negative pathogen that employs different strategies (resistance and persistence) to counteract antibiotic treatments. This study aimed to search for new means of combatting imipenem-resistant and persister strains of K. pneumoniae by repurposing the anticancer drug mitomycin C as an antimicrobial agent and by combining the drug and the conventional antibiotic imipenem with the lytic phage vB_KpnM-VAC13. Several clinical K. pneumoniae isolates were characterized, and an imipenem-resistant isolate (harboring OXA-245 β-lactamase) and a persister isolate were selected for study. The mitomycin C and imipenem MICs for both isolates were determined by the broth microdilution method. Time-kill curve data were obtained by optical density at 600 nm (OD600) measurement and CFU enumeration in the presence of each drug alone and with the phage. The frequency of occurrence of mutants resistant to each drug and the combinations was also calculated, and the efficacy of the combination treatments was evaluated using an in vivo infection model (Galleria mellonella). The lytic phage vB_KpnM-VAC13 and mitomycin C had synergistic effects on imipenem-resistant and persister isolates, both in vitro and in vivo. The phage-imipenem combination successfully killed the persisters but not the imipenem-resistant isolate harboring OXA-245 β-lactamase. Interestingly, the combinations decreased the emergence of in vitro resistant mutants of both isolates. Combinations of the lytic phage vB_KpnM-VAC13 with mitomycin C and imipenem were effective against the persister K. pneumoniae isolate. The lytic phage-mitomycin C combination was also effective against imipenem-resistant K. pneumoniae strains harboring OXA-245 β-lactamase.


A common standard for conflict of interest disclosure in addiction journals.
This paper presents a common standard for conflict of interest disclosure. The common standard was drafted by the authors, following consultation with a multi-disciplinary group of journal editors, publishers, bioethicists and other academics. It is presented here for the benefit of authors, editorial managers, journal editors and peer reviewers to stimulate discussion and to provide guidance to authors in reporting real, apparent and potential conflicts of interest. It is particularly relevant to addiction specialty journals because of the potential conflicts of interest associated with funding from the alcohol, tobacco, pharmaceutical and gambling industries. Following an appropriate period of vetting the common standard within the scientific community, it is recommended that journal editors adopt journal policies and reporting procedures that are consistent across journals.


East Coast fever: cultivation in vitro of cell-free schizonts and merozoites of Theileria parva and their immunogenicity in cattle.
Cell-free schizonts and merozoites of Theileria parva and Theileria lawrencei, derived from parasitized lymphoid cell lines, were propagated in vitro using enriched medium. Use of radioisotopic markers showed that the bovine cell-independent parasites passed through a limited but marked replication by day 4. If normal bovine RBC were inoculated in vitro with the cell-free merozoites, development of piroplasms in the RBC occurred. Electron microscopic studies of the merozoites and piroplasms revealed their structure to be similar to previous descriptions. Cattle inoculated with T parva merozoites and schizonts and later challenge exposed with homologous stabilate developed leukopenia, showed low macroschizont index, and survived longer than unvaccinated controls.


LIS1 regulates osteoclast formation and function through its interactions with dynein/dynactin and Plekhm1.
Microtubule organization and lysosomal secretion are both critical for the activation and function of osteoclasts, highly specialized polykaryons that are responsible for bone resorption and skeletal homeostasis. Here, we have identified a novel interaction between microtubule regulator LIS1 and Plekhm1, a lysosome-associated protein implicated in osteoclast secretion. Decreasing LIS1 expression by shRNA dramatically attenuated osteoclast formation and function, as shown by a decreased number of mature osteoclasts differentiated from bone marrow macrophages, diminished resorption pits formation, and reduced level of CTx-I, a bone resorption marker. The ablated osteoclast formation in LIS1-depleted macrophages was associated with a significant decrease in macrophage proliferation, osteoclast survival and differentiation, which were caused by reduced activation of ERK and AKT by M-CSF, prolonged RANKL-induced JNK activation and declined expression of NFAT-c1, a master transcription factor of osteoclast differentiation. Consistent with its critical role in microtubule organization and dynein function in other cell types, we found that LIS1 binds to and colocalizes with dynein in osteoclasts. Loss of LIS1 led to disorganized microtubules and aberrant dynein function. More importantly, the depletion of LIS1 in osteoclasts inhibited the secretion of Cathepsin K, a crucial lysosomal hydrolase for bone degradation, and reduced the motility of osteoclast precursors. These results indicate that LIS1 is a previously unrecognized regulator of osteoclast formation, microtubule organization, and lysosomal secretion by virtue of its ability to modulate dynein function and Plekhm1.


Evaluation of renal function.
The patient's history, physical examination, and routine urinalysis (including an expert assessment of the urinary sediment) are of paramount importance for the evaluation of a patient with possible renal dysfunction. The four tests most commonly used to establish the presence, extent, and the rate of progression of renal dysfunction are BUN, PCr, CCr, and 24-hour protein excretion. All four tests reflect glomerular function. However, their use to evaluate general renal function is justified by the structural and functional interdependence of tubular and vascular elements of the kidney.


Rapid changes in liver lipid composition and pancreatic islet K+ handling and secretory behaviour provoked by the intravenous administration of a medium-chain triglyceride: fish oil emulsion to long-chain polyunsaturated omega3 fatty acid-depleted rats.
Second generation rats depleted in long-chain polyunsaturated omega3 fatty acids are currently used as an animal model for the insufficient dietary supply of such fatty acids often prevailing in Western populations. The present study deals mainly with the effects of a novel medium-chain triglyceride: fish oil emulsion (MCT:FO), as compared to a control medium-chain triglyceride:olive oil emulsion (MCT: OO), administered as an intravenous bolus to the omega3-depleted rats 60-120 min before sacrifice upon selected biochemical and biophysical variables. The major findings consisted of a severe decrease of the omega3 fatty acid content of liver lipids in non-injected omega3-depleted rats and its partial correction after injection of the MCT:FO emulsion. The omega3-depleted rats also displayed liver steatosis, increased incorporation of long-chain polyunsaturated omega6 fatty acids in liver phospholipids and increased activity of liver Delta9-desaturase. As judged from the effects of ouabain upon 86Rb net uptake by isolated pancreatic islets, the activity of Na+,K+-ATPase was virtually abolished in the omega3-depleted rats. The latter defect was corrected by prior intravenous injection of the MCT:FO emulsion, this coinciding with suppression of the excessive secretory response to a number of insulin secretagogues otherwise observed in the islets of omega3-depleted rats injected or not with the MCT:OO emulsion.


[Suicide by intravenous injection of rocuronium-bromide--case report].
Suicides by intravenous injection of an overdose of medicaments are uncommon. In this paper, we present the case of a suicide by rocuronium-bromide injection in combination with an oral overdose of metoprolol. Unfortunately, in Belgrade, there is no toxicological laboratory capable of detecting rocuronium. The interpretation of autopsy and toxicological data in this case was made difficult due to the extreme putrefaction of the body of the deceased. So, by forensic investigation, the case was solved indirectly, through circumstantial evidence: an empty ampoule of rocuronium found near the body, as well as a plastic syringe and cloth-bandage found in the left hand of the deceased.


Guideline compliance improves pneumonia care.
Expanding your standard practices can change staff behavior in the treatment of patients, as demonstrated by study of pneumonia care in 32 EDs. Repeat important information more often than you normally do. When staff do not follow procedure, take them aside and discuss the situation. Share mistakes with the rest of the staff, without identifying the one who made the error.


Role of cytochrome P-450 and flavin-containing monooxygenase in the N-hydroxylation of N-methyl-4-aminoazobenzene in rat liver: analysis with purified enzymes and antibodies.
By means of high pressure liquid chromatography, the role of flavin-containing monooxygenase (FMO) and cytochrome P-450 (cyt. P-450) in the metabolism of N-methyl-4-aminoazobenzene (MAB) by rat liver microsomes in vitro was studied with the help of antibodies and a chemical inhibitor. Antibody against cyt. P-488 from 3-methylcholanthrene-treated rats (MC-P-448) decreased the formation of N-hydroxy-N-methyl-4-aminoazobenzene (N-OH-MAB) by about 30% in microsomes from MC-treated rats (MC-microsomes), but showed no inhibitory effect on the formation of N-OH-MAB in microsomes from untreated rats (untreated microsomes) or in microsomes from phenobarbital-treated rats (PB-microsomes). Antibody against cyt. P-450 from PB-treated rats did not inhibit N-hydroxylation of MAB by any of the microsomes tested. A competitive inhibitor of FMO, methimazole, inhibited the N-hydroxylation of MAB by 65% in the case of MC-microsomes, and the residual activity was inhibited completely by anti-NADPH-cytochrome P-450 reductase (anti-fPT) antibody. These results indicate that in MC-microsomes, the N-hydroxylation of MAB is catalyzed by both FMO and MC-P-448, but in untreated and PB-microsomes the reaction is catalyzed exclusively by FMO.


Maturational changes in arterial impedance of the normal testis in boys: Doppler sonographic study.
The use of color Doppler sonography to diagnose scrotal disorders in children has been hampered by the small size of the vessels and the slow blood flow compared with those in adults. Spectral analysis is the best means available of confirming the vascular origin of questionable color-flow signals arising from testes of small volume. The range of normal and abnormal Doppler sonographic arterial waveforms arising from the testis in boys, as distinct from those in adults, has never been described. The purpose of our study was to establish the normal range of testicular arterial impedance, measured as resistive index (RI), in both prepubertal and pubertal/post pubertal boys. Bilateral scrotal color Doppler sonography was performed in 33 healthy boys aged 3 days to 17.5 years. The mean RI in the parenchymal artery was measured in 44 testes and plotted against testicular volume. Chi-square statistics were used to test differences in mean RI, testicular volume, and age between testes with volumes of 4 cm3 or less and testes with volumes greater than 4 cm3. In testes with volumes of 4 cm3 or less, the mean RI ranged from 0.39 to 1.00 (mean, 0.87), and in testes with volumes greater than 4 cm3, the RI ranged from 0.43 to 0.75 (mean, 0.57). In 20 of 30 testes with volumes of 4 cm3 or less, the RI of parenchymal arteries was equal to 1.00 (i.e., diastolic flow was undetectable). Mean RI, testicular volume, and age were significantly different between testes with volumes of 4 cm3 or less and testes with volumes greater than 4 cm3 (p < .001 for all variables). Mean testicular RI in our samples of pubertal and postpubertal boys is decreased compared with the mean RI in prepubertal boys. Diastolic arterial flow may not be detectable in normal testes with volumes of 4 cm3 or less. Despite the existence of a statistically significant difference in mean RI between prepubertal and pubertal/postpubertal testes, substantial variability exists within each group, particularly among the prepubertal testes. Norms of testicular flow previously established for adults are therefore not routinely applicable to prepubertal boys with testicular volumes less than 4 cm3. However, RI values in normal pubertal and postpubertal boys where testicular volumes exceed 4 cm3 are comparable to those previously described in adults.


Sensory analysis and species-specific PCR detect bovine milk adulteration of frescal (fresh) goat cheese.
The Brazilian market for dairy products made from goat milk is increasing despite the seasonality of production and naturally small milk production per animal, factors that result in high-priced products and encourage fraud. In Brazil, no official analytical method exists for detecting adulteration of goat dairy products with cow milk. The aim of this study was to design a strategy to investigate the adulteration of frescal (fresh) goat cheeses available in the Rio de Janeiro retail market, combining analysis of cheese composition and the perception of adulteration by consumers. Commercial goat cheeses were tested by using a duplex PCR assay previously designed to authenticate cheeses, by targeting the mitochondrial 12S ribosomal RNA genes of both species simultaneously. The PCR test was able to detect 0.5% (vol/vol) cow milk added during goat cheese formulation. The analysis of 20 locally produced goat cheeses (20 lots of 4 brands) showed that all were adulterated with cow milk, even though the labels did not indicate the addition of cow milk. To estimate the ability of consumers to perceive the fraudulent addition of cow milk, a triangle test was performed, in which cheeses formulated with several different proportions of goat and cow milk were offered to 102 regular consumers of cheese. Detection threshold analysis indicated that almost half of the consumers were able to perceive adulteration at 10% (vol/vol) cow milk. Effective actions must be implemented to regulate the market for goat dairy products in Brazil, considering the rights and choices of consumers with respect to their particular requirements for diet and health, preference, and cost.


Organocatalyzed Sulfa-Michael Addition of Thiophenols on Trisubstituted α-Fluoroacrylates, a Straightforward Access to Chiral Fluorinated Compounds.
In this manuscript, a simple and efficient sulfa-Michael addition reaction of aryl thiols to trisubstituted α-fluoro-α,β-unsaturated esters both in racemic and, for the first time, in enantioselective version is reported. The commercially available dimer of cinchona derivatives (DHQ)2PYR was used as a catalyst. This strategy showed a great tolerance for various substrates and substituents, providing fair to excellent yields, moderate to excellent diastereoselectivities (2:1 to >99:1), and low to good enantioselectivities (2 to 87%). The reaction has been applied to the synthesis of fluorinated analogues of diltiazem and tiazesim, both therapeutic agents.


Reduced expression of the endothelin receptor type B gene in piebald mice caused by insertion of a retroposon-like element in intron 1.
Mice carrying the piebald mutation exhibit white coat spotting due to the regional absence of neural crest-derived melanocytes. We reported previously that the piebald locus encodes the Ednrb gene and that piebald mice express low levels of structurally intact Ednrb mRNA and EDNRB protein (Hosoda, K., Hammer, R. E., Richardson, J. A., Baynash, A. G., Cheung, J. C., Giaid, A., and Yanagisawa, M. (1994) Cell 79, 1267-1276). Here, we report that both the life span of the Ednrb mRNA and the promoter activity of the Ednrb gene are indistinguishable between wild-type and piebald mice. Introns 2-6 of the Ednrb gene in piebald mice were correctly excised with an efficiency indistinguishable from those in wild-type mice in exon trapping experiments. We found that the piebald allele of the Ednrb gene has a 5.5-kb retroposon-like element in intron 1 possessing canonical sequences of a polyadenylation signal and a splice acceptor site. Abnormal hybrid transcripts carrying exon 1 of the Ednrb gene and a portion of the 5.5-kb element are expressed in piebald mice. The insertion of the 5.5-kb element into a heterologous intron in a mammalian expression vector markedly reduced the expression of the reporter gene. Premature termination and aberrant splicing of the Ednrb transcript caused by the retroposon-like element in intron 1 lead to a reduced level of the normal Ednrb transcript, which is responsible for the partial loss-of-function phenotype of piebald mice.


Understanding the mechanism of non-polar Diels-Alder reactions. A comparative ELF analysis of concerted and stepwise diradical mechanisms.
The electron-reorganization along the concerted and stepwise pathways associated with the non-polar Diels-Alder reaction between cyclopentadiene (Cp, 1) and ethylene (2) has been studied using the topological analysis of the electron localization function (ELF) at the B3LYP/6-31G(d) level of theory. ELF results for the concerted mechanism stresses that the electron-reorganization demanded on the diene and ethylene reagents to reach two pseudo-diradical structures is responsible for the high activation energy. A comparative ELF analysis of some relevant points of the non-polar Diels-Alder reaction between Cp and styrene (10) suggests that these concerted mechanisms do not have a pericyclic electron-reorganization.


Effects of neuromuscular electrical stimulation in patients with Parkinson's disease and dysphagia: A randomized, single-blind, placebo-controlled trial.
Neuromuscular electrical stimulation has been used to improve swallowing function in neurologic patients with dysphagia, but its effect on patients with dysphagia and Parkinson's disease remains unclear. This study aimed to identify the effect of effortful swallowing combined with neuromuscular electrical stimulation as a novel treatment approach in dysphagic patients with Parkinson's disease. Participants were randomly allocated to an experimental group (n = 9) or a placebo group (n = 9). The experimental group simultaneously received neuromuscular electrical stimulation with effortful swallowing, while the placebo group received sham neuromuscular electrical stimulation with effortful swallowing. All participants received the treatment for 30 min/day at five sessions per week for 4 weeks. Both groups also received the same conventional dysphagia therapy. The experimental group showed significant differences in horizontal movement (p = 0.038) and vertical movement (p = 0.042) compared to the placebo group, but showed no significant differences in the oral (p = 0.648) or pharyngeal phase (p = 0.329) of the Videofluoroscopic Dysphagia Scale compared to the placebo group, except for the Penetration-Aspiration Scale (p = 0.039). We demonstrated that neuromuscular electrical stimulation applied to the infrahyoid region combined with effortful swallowing effectively increased hyoid bone movement and reduced aspiration in dysphagic patients with Parkinson's disease.


Lysine Bioconjugation on Native Albumin with a Sulfonyl Acrylate Reagent.
This protocol details a novel bioconjugation strategy that uses a methanesulfonyl acrylate reagent that is directed to the most reactive lysine on human serum albumin, which enables the construction of chemically defined and stable bioconjugates. The reaction proceeds rapidly and a regioselective modification is achieved using a single molar equivalent of the reagent under biocompatible conditions (37 °C, pH 8.0). Importantly, the bioconjugate retains both the secondary structural content and function of the unmodified protein. During the reaction of the amino group of lysine and the sulfonyl acrylate reagent, methanesulfinic acid is released after the conjugate addition, which then generates an electrophilic acrylate moiety on the protein. This acrylate can be further used for site-specific protein labeling using a synthetic molecule bearing a reactive amine under biocompatible conditions (21 °C, pH 8.0).


Vaccinations in pediatric kidney transplant recipients.
Pediatric kidney transplant (KT) candidates should be fully immunized according to routine childhood schedules using age-appropriate guidelines. Unfortunately, vaccination rates in KT candidates remain suboptimal. With the exception of influenza vaccine, vaccination after transplantation should be delayed 3-6 months to maximize immunogenicity. While most vaccinations in the KT recipient are administered by primary care physicians, there are specific schedule alterations in the cases of influenza, hepatitis B, pneumococcal, and meningococcal vaccinations; consequently, these vaccines are usually administered by transplant physicians. This article will focus on those deviations from the normal vaccine schedule important in the care of pediatric KT recipients. The article will also review human papillomavirus vaccine due to its special importance in cancer prevention. Live vaccines are generally contraindicated in KT recipients. However, we present a brief review of live vaccines in organ transplant recipients, as there is evidence that certain live virus vaccines may be safe and effective in select groups. Lastly, we review vaccination of pediatric KT recipients prior to international travel.


A systematic review and meta-analysis of treatment for hepatorenal syndrome with traditional Chinese medicine.
Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver diseases. It has been reported that traditional Chinese medicine (TCM) may improve liver function, delay disease progression, alleviate symptoms, and improve quality of life in HRS patients. The study aims to systematically review the efficacy of TCM for the treatment of HRS. Publications were searched electronically from China National Knowledge Infrastructure (CNKI), Wanfang, VIP, PubMed, and EMBASE databases. Odds ratio (OR) and standardized mean difference (SMD) with 95% confidence interval (CI) were calculated. Heterogeneity was assessed. The Cochrane Collaboration's tool was used to assess the risk of bias. Fourteen randomized controlled trials involving 788 patients with HRS were included. Random generation sequence was reported in only two studies. Blinding was not used in any study. Compared to conventional treatment without TCM, TCM led to a significant survival benefit during hospitalization (OR: 0.18; 95% CI: 0.08-0.39; P<0.0001), a significantly higher complete response (OR: 3.20; 95% CI: 2.06-4.97; P<0.00001), and a significantly lower no response (OR: 0.20; 95% CI: 0.14-0.30; P<0.00001). Partial response was not significantly different between the two groups (OR: 1.39; 95% CI: 0.90-2.15; P=0.14). Regardless of TCM, blood urea nitrogen and abdominal circumference were significantly decreased, and urine volume was significantly increased after treatment. Compared to conventional treatment without TCM, TCM led to a significantly lower serum creatinine, blood urea nitrogen, bilirubin, plasma ammonia, and abdominal circumference and significantly higher urine volume after treatment. There was significant heterogeneity. TCM might have a better survival and a higher complete response in patients with HRS. However, the quality of published studies was unsatisfactory.


Recent Development of Non-Peptide GnRH Antagonists.
The decapeptide gonadotropin-releasing hormone, also referred to as luteinizing hormone-releasing hormone with the sequence (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH₂) plays an important role in regulating the reproductive system. It stimulates differential release of the gonadotropins FSH and LH from pituitary tissue. To date, treatment of hormone-dependent diseases targeting the GnRH receptor, including peptide GnRH agonist and antagonists are now available on the market. The inherited issues associate with peptide agonists and antagonists have however, led to significant interest in developing orally active, small molecule, non-peptide antagonists. In this review, we will summarize all developed small molecule GnRH antagonists along with the most recent clinical data and therapeutic applications.


From experimental rat hindlimb to clinical face composite tissue allotransplantation: historical background and current status.
The purpose of this article is to review the historical background and clinical status of composite tissue allotransplantation and to discuss the scientific evolution of clinical face transplantation. Composite tissue allotransplantation (CTA) rapidly progressed in the 1980s with the discovery of cyclosporine. Although the most success has been achieved with hand transplantation, others have made progress with allografts of trachea, peripheral nerve, flexor tendon apparatus, vascularized knee, larynx, abdominal wall, and most recently, partial face. The world's first partial face allotransplantation occurred in November 2005 in France. In April of 2006, there was a second performed in China. As of today, there are now multiple institutions with plans to attempt the world's first full facial/scalp transplant. Complete facial/scalp allotransplantation offers a viable alternative for unfortunate individuals suffering severe facial disfigurement and is a product of many decades of experimental research, beginning with rat hindlimb allografts.


Living with the health and social inequities of a disability: a critical feminist study.
Clients living at home with chronic disabling conditions together with their caregivers, service providers, and policymakers face major challenges in optimizing health care. In this critical feminist interpretive study we examined the experiences of women receiving home care for chronic disabling conditions. Five themes emerged: struggling with the embodied limitations of disabling chronic conditions; actively seeking health; struggling with service limitations; seeking ways to manage; and living with isolation and marginalization. Having done this study, we learned that home care services do not always contribute sufficiently to the overall health and well-being of women living with chronic disabling conditions and, in fact, may negatively impact upon their health.


Cervicogenic exophthalmos: Possible etiology and pathogenesis.
Unilateral exophthalmos is often caused by inflammation, neoplasm, infection, metabolic disease, vascular disorder and several other less common conditions. Reflex sympathetic dystrophy related to unilateral exophthalmos has not been reported in the past literature. We describe a 45-year-old female with unilateral exophthalmos caused by reflex sympathetic dystrophy and its unexpected spontaneous disappearance after a standard anterior cervical discectomy and fixation operation with two PEEK interbody cages and a plate. To our surprise, the patient's left unilateral exophthalmos improved spontaneously in the morning on postoperative day 2-with no relapse, without any further medication, as of seven years. We have named this condition "cervicogenic exophthalmos." We would inform other clinicians that unilateral exophthalmos was caused not only by inflammation, vascular disorder, infection, neoplasm, or metabolic disease, but also by reflex sympathetic dystrophy related with cervicogenic spondylosis. To the best of our knowledge, ours is the first related case report and use of the term "cervicogenic exophthalmos" after reviewing previous literature.


Do hospital doctors test for thrombophilia in patients with venous thromboembolism?
The predictive value of factor V Leiden and the G20210A prothrombin mutation regarding recurrent venous thromboembolism (VTE) is limited and does not influence subsequent patient management. Systematic testing for such genetic thrombophilia should be avoided, but to which extent such testing is practiced in a Swiss Hospital is unknown. To examine the current practice of factor V Leiden and/or G20210A prothrombin mutation testing in a University Hospital, and to assess the clinical consequences of testing on patients. 1388 adult patients (48.7% women) with a main diagnosis of VTE hospitalized at the Lausanne university hospital between January 2013 and December 2015. FV Leiden and/or prothrombin G20210A mutation testing was performed in 61 (4.4%) patients with VTE, an average of 20 patients/year. On multivariable analysis, age < 65 years [odds ratio and (95% confidence interval) 5.91 (3.12-11.19)], being admitted in a medical ward [5.71 (2.02-16.16)] and staying in the intensive care unit [0.34 (0.12-0.97)] were associated with thrombophilia testing. No differences were found between patients with and without testing regarding in-hospital mortality [OR and 95% CI for tested vs. non-tested: 0.23 (0.03-1.73), p = 0.153] and length of stay (multivariable adjusted average ± standard error: 16.9 ± 3.3 vs. 20.0 ± 0.7 days for tested and non-tested patients, respectively, p = 0.875). Thrombophilia testing in hospitalized patients with a main diagnosis of VTE is seldom performed. FV Leiden and/or prothrombin G20210A mutation should not be routinely assessed in patients with acute VTE.


A fluorescent probe for biothiols based on the conjugate addition of thiols to α,β-unsaturated ester.
A sensitive fluorogenic probe 1 for biothiols was developed based on the Michael addition reaction. The probe 1 was readily synthesized via the reaction of 2-(4'-hydroxyphenyl) benzimidazole (HPBI) with acryloyl chloride and shows weak fluorescence emission. Upon mixing with biothiols, the fluorescence of 1 is significantly enhanced due to the conjugate addition of thiols to the α,β-unsaturated carbonyl moiety, thus eliminating the photoinduced electron transfer (PET) quenching of the fluorophore by the intramolecular carbon-carbon double bond. Cysteine (Cys) was selected as the representative thiol in the spectral experiment. A good linear relationship was obtained from 1.0 to 30.0 µmol L(-1) for Cys and the detection limit was 0.17 µmol L(-1). Furthermore, probe 1 was highly selective for biothiols without the interference of some biologically relevant analytes and has been applied to detecting biothiols in human urine samples.


[Viral diseases as a predisposing factor of developing secondary oto- and rhinogenic bacterial meningitis].
Effects of viruses and bacterial associations are suggested to promote secondary purulent intracranial complications in ENT patients. Fundamental aspects of pathogenesis of viral neuroinfections and pathogenetic mechanisms of different conditions provoked by viral factors promoting bacterial complications are presented. Hemoculture, and cerebrospinal fluid in 24 patients with secondary purulent rhinogenic and otogenic meningitis were studied with polymerase chain reaction for enteroviruses, cytomegaloviruses, Epstein-Barr, herpes, zoster viruses. The viruses were present in the studied media in 29.4% samples.


Differentiation of meat species of raw and processed meat based on polar metabolites using 1H NMR spectroscopy combined with multivariate data analysis.
Meat species of raw meat and processed meat products were investigated by 1H NMR spectroscopy with subsequent multivariate data analysis. Sample preparation was based on aqueous extraction combined with ultrafiltration in order to reduce macromolecular components in the extracts. 1H NMR data was analyzed by using a non-targeted approach followed by principal component analysis (PCA), linear discrimination analysis (LDA), and cross-validation (CV) embedded in a Monte Carlo (MC) resampling approach. A total of 379 raw meat samples (pork, beef, poultry, and lamb) and 81 processed meat samples (pork, beef, poultry) were collected between the years 2018 and 2021. A 99% correct prediction rate was achieved if the raw meat samples were classified according to meat species. Predicting processed meat products was slightly less successful (93 %) with this approach. Furthermore, identification of spectral regions that are relevant for the classification via polar chemical markers was performed. Finally, data on polar metabolites were fused with previously published 1H NMR data on non-polar metabolites in order to build a broader classification model and to improve prediction accuracy.


Major differences in oral health knowledge and behavior in a group of Iranian pre-university students: a cross-sectional study.
To establish efficient methods for self-prevention of oral diseases, assessment of dental health behavior and knowledge in various social classes is necessary. The main purpose of this study was to determine the major differences in oral health knowledge and behavior in a group of Iranian pre-university students. In this cross-sectional study, 591 pre-university students from different regions of Mashhad, Iran were randomly selected to complete a questionnaire consisting of two parts including dental health behavior and knowledge. Scores were recorded and statistical analyses performed to determine the correlation between dental health behavior and knowledge. Data was analyzed with Student's t-test, one-way analysis of variance and Pearson correlation. The mean score of dental health knowledge was significantly lower than the dental health behavior (2.95 ± 0.02 vs. 3.31 ± 0.05, P < 0.001). This difference was observed with gender, birth location and major subject of study. The dental health behavior of Iranian pre-university students was inadequate and their dental health knowledge was at a lower level compared to their behavior. Experimental science students had better oral health behavior compared to other students.


Small intestinal transit in the portal hypertensive rat.
The purpose of this study was to determine the effects of portal hypertension on gastrointestinal transit. Portal hypertension was induced in a group of 15 rats by the staged portal vein ligation technique. A control group of 15 rats underwent a sham operation. Ten days later, a 51Cr-labeled Krebs' buffer solution was instilled into the duodenum and the distribution or radioactivity along the length of the small intestine was determined after 15, 30, and 60 minutes. Portal hypertension was consistently established in the study group; splenic pulp pressure (mm Hg, mean +/- SD, portal hypertensive vs. control) was 20.0 +/- 3.9 vs. 12.7 +/- 3.9, P less than 0.002. Various measures of intestinal transit revealed delayed transit in the portal hypertensive group. Retention of radioactivity in the most proximal quartile of the intestine was greater [percentage retained (portal hypertensive vs. control) was 57.9 +/- 17.3 vs. 31.2 +/- 15.3, P less than 0.02, 49.1 +/- 15.5 vs. 28.3 +/- 4.8, P = 0.03, and 42.4 +/- 17.6 vs. 29.0 +/- 8.8, P = 0.08, at 15, 30, and 60 minutes, respectively] and the geometric mean of transit was located more proximally (P less than 0.02) at each study interval in the portal hypertension group. It was concluded that portal hypertension is associated with delayed intestinal transit. This abnormality could predispose to bacterial overgrowth and contribute to altered digestion and absorption.


Optimizing dialysis delivery in tunneled dialysis catheters.
Long-term dialysis is often delivered through tunneled central venous catheters (CVC) despite their associated morbidity and mortality rates. Because poor solute clearance might contribute to this risk, we examined the relation between blood pump speed (QB), access recirculation (AR), and dialysis delivery in patients with CVC. We conducted a prospective study on 102 patients receiving long-term hemodialysis with CVC. QB was systematically varied, and AR was measured by saline dilution with the blood supply lines in both the straight and the reversed positions during each of two dialysis sessions. During a third session, we measured ionic dialysance (EID) in patients with AR>0% and those in whom dialysis was usually delivered with catheters in the reversed position.Approximately one third (34.3%) of patients were usually run in the reversed position. Clinically significant AR (>10%) was infrequent (3%) in the straight position but common in the reversed position (86%). QB and EID were linearly correlated for both the straight and reversed positions. Approximately half (48.6%) of patients who were generally treated with their lines reversed were able to receive dialysis with the lines in the straight position within acceptable pressure limits when blood lines were switched part way through the run. In these patients, solute clearance was equivalent (EID straight 204 ml/min vs. reversed 196 ml/min, p=0.58) with lines in the straight configuration despite lower achieved QB (straight 354 ml/min vs. reversed 404 ml/min, p=0.04). Maximization of prescribed QB in CVC increased AR when blood line position was reversed but improved small solute clearance regardless of line position. This suggests that QB in CVC should be set as high as circuit pressure limits will allow, regardless of the potential for AR, and that reversal of line position confers no benefit with respect to solute clearance.


The valuation of the International Prostate Symptom Score (IPSS) for use in economic evaluations.
Lower Urinary Tract Symptoms (LUTS) suggestive of Benign Prostatic Obstruction (BPO) cause a reduction in quality of life, but the magnitude of that reduction cannot be estimated empirically. This is because survey instruments currently available merely sum the symptoms found, but do not value their impact on quality of life. It is therefore difficult to determine whether the effects of treatments for LUTS suggestive of BPO justify the costs. This complicates economic evaluations. We valued the impact on quality of life of patients with LUTS suggestive of BPO, by valuing health states defined by the International Prostate Symptom Score (IPSS) using the time trade-off (TTO). TTO values ranged from 1.0 for perfect health to 0.0 for the value of death, and can be used to calculate Quality-Adjusted Life Years (QALYs), the preferred outcome measure in health economics. We reduced the number of health states defined by the IPSS using factor analysis. The resulting nine health states were valued by a representative sample of the general public (N=170) using TTO. The worst IPSS health state was valued at 0.87. The values for health states defined by the IPSS revealed that LUTS suggestive of BPO has a mild impact on quality of life. The valuation of the IPSS facilitates economic evaluations of treatments for LUTS suggestive of BPO, because QALYs (the preferred outcome measure in health economics) can be determined empirically.


Group body psychotherapy for the treatment of somatoform disorder - a partly randomised-controlled feasibility pilot study.
Clinical outcomes for patients with heterogeneous somatoform disorder (bodily distress disorder, including medically unexplained symptoms) are suboptimal, new treatments are required to improve acceptance. Body-oriented psychological therapy approaches have been identified as potentially beneficial additions to the portfolio of treatments. This study was aiming to assess the acceptability, the potential benefits, and associated change processes of manualised group body psychotherapy (BPT) for outpatients with Somatoform Disorder. A randomized controlled feasibility trial was carried out with follow-up at 6 months after baseline assessments using the Primary Health Questionnaire (PHQ), Somatic Symptom Screening Scale (SOMS-7), quality of life ratings (Short-Form Health Survey-36; SF-36) and body image measures (Dresden Body Image Questionnaire). Acceptance was assessed with the Helping Alliance Scale (HAS). A total of 24 patients were recruited to participate. Sixteen patients were randomly assigned to receive either manualised BPT or TAU, eight patients were directly assigned to BPT. Drop-out rates were acceptable, patients reported to be highly satisfied with the group intervention. Somatic symptom levels reduced significantly in the BPT group. Additionally, a significant effect on self-acceptance and the mental component of quality of life was observed. Group body psychotherapy is a feasible and acceptable treatment for patients with somatoform disorder and a larger trial studying the effectiveness of BPT in these patients should be conducted. Retrospectively registered SRCTN12277345 ; Trial Registraton Date: 27/03/2019.


Effects of spatial and temporal variation in metal availability on earthworms in floodplain soils of the river Dommel, The Netherlands.
Regarding impact on ecological soil functioning, metal pollution is often considered a constant factor for certain sampling sites. However, especially bioavailable concentrations may differ in space and time. This aspect was investigated on four sites along a metal-polluted river, differing in soil characteristics and metal concentrations. Every four weeks earthworm densities, soil characteristics, and metal concentrations in soil and earthworms were determined. Earthworm biomass and density fluctuated in time and increased with increasing metal contamination, indicating the presence of compensating factors. Multivariate analysis suggested organic matter and moisture content to be the main factors explaining earthworm biomass. Metal concentrations in the earthworms increased with increasing total or 0.01M CaCl(2) extractable soil concentrations, but no time-related trends were seen. Cadmium concentrations in the earthworms exceeded background values, suggesting a potential risk. The neutral red retention biomarker assay, however, did not show any signs of metal stress in the earthworms.


Old but not obsolete: A new life for some of Murrill's (Hebeloma) names.
William Alphonso Murrill was an American mycologist of the early 20th century. He described 1453 new species of Agaricales, Boletales, and Polyporales. Within these were 44 taxa that he described as Hebeloma or that he recombined into Hebeloma. Additionally, there are five species, of which we are aware, that Murrill described within other genera that should be referred to the genus Hebeloma. A further three species described from northern America by J. P. F. C. Montagne, and transferred to Hebeloma by Saccardo, were commented on by Murrill and not accepted within the genus. These 52 taxa are analyzed here, both morphologically and molecularly, as far as possible. For 18 of his types, internal transcribed spacer (ITS) sequences were generated. For two species (H. harperi and H. subfastibile), which were mixed collections, lectotypes are designated. Twenty-three of the taxa analyzed are Hebeloma, as the genus is recognized today, and six of these (H. australe, H. harperi, H. paludicola, H. subaustrale, H. subfastibile, and H. viscidissimum) are regarded as current, i.e., they are names that should be accepted and used. Hebeloma paludicola is an earlier name for H. hygrophilum, described from Europe. Gymnopilus viscidissimus is synonymous with H. amarellum but has priority and is here recombined into Hebeloma. The remaining 17 Hebeloma taxa are synonymized with other species that have priority. The remaining 29 species belong to a range of genera; molecularly supported were Agrocybe, Cortinarius, Inocybe, Inosperma, Phlegmacium, Pholiota, Pseudosperma, and Pyrrhulomyces. Recombinations and synonymizations are made as appropriate and necessary. The names H. alachuanum and H. vatricosum, respectively Inocybe vatricosa, are considered doubtful and should be avoided.


Challenges in funding diabetes care: a health economic perspective.
Diabetes mellitus - especially Type 2 diabetes - represents a major threat to public health in nearly all countries worldwide. The number of patients with diabetes is expected to rise to over 438 million by the year 2030. As healthcare resources are considered limited, there is a need for prioritization among the different, existing therapeutic options available for treating or preventing diseases in a given healthcare system. This article will highlight five particular challenges for evaluating complex therapeutic approaches in diabetes care, introducing the health economic fundamentals of cost-effectiveness assessment and the different concepts to determine a cost-effectiveness threshold, with a special focus on the situation in low- and middle-income countries.


Ischemic preconditioning inhibits mitochondrial respiration, increases H2O2 release, and enhances K+ transport.
Ischemic preconditioning, or the protective effect of short ischemic episodes on a longer, potentially injurious, ischemic period, is prevented by antagonists of mitochondrial ATP-sensitive K+ channels (mitoKATP) and involves changes in mitochondrial energy metabolism and reactive oxygen release after ischemia. However, the effects of ischemic preconditioning itself on mitochondria are still poorly understood. We determined the effects of ischemic preconditioning on isolated heart mitochondria and found that two brief (5 min) ischemic episodes are sufficient to induce a small but significant decrease ( approximately 25%) in mitochondrial NADH-supported respiration. Preconditioning also increased mitochondrial H2O2 release, an effect related to respiratory inhibition, because it is not observed in the presence of succinate plus rotenone and can be mimicked by chemically inhibiting complex I in the presence of NADH-linked substrates. In addition, preconditioned mitochondria presented more substantial ATP-sensitive K+ transport, indicative of higher mitoKATP activity. Thus we directly demonstrate that preconditioning leads to mitochondrial respiratory inhibition in the presence of NADH-linked substrates, increased reactive oxygen release, and activation of mitoKATP.


Image-guided versus blind corticosteroid injections in adults with shoulder pain: a systematic review.
Corticosteroid injections can be performed blind (landmark-guided) or with image guidance, and this may account for variable clinical outcomes. The objective of this study was to assess the effectiveness and safety of image-guided versus blind corticosteroid injections in improving pain and function among adults with shoulder pain. MEDLINE, the Cochrane Controlled Trials Register and EMBASE were searched to May 2010. Additional studies were identified by searching bibliographies of shortlisted articles. Search items included blind, landmark, anatomical, clinical exam, image-guided, ultrasound, fluoroscopy, steroid injection, frozen shoulder, random allocation, randomized controlled trial (RCT) and clinical trial.Randomized controlled studies comparing image-guided versus blind (landmark-guided) corticosteroid shoulder injections that examined pain, function and/or adverse events were included. Independent extraction was done by two authors using a form with pre-specified data fields, including risk of bias appraisal. Conflicts were resolved by discussion. The decision to pool data was based on assessment of clinical design homogeneity. When warranted, studies were pooled under a random-effects model. Two RCTs for pain, function and adverse events (n = 101) met eligibility criteria. No serious threats to validity were found. Both trials compared ultrasound-guided versus landmark-guided injections and were judged similar in clinical design. Low to moderate heterogeneity was observed: shoulder pain I2 = 60%, function I2 = 22%. A meta-analysis demonstrated greater improvement with ultrasound-guided injections at 6 weeks after injection in both pain (mean difference = 2.23 [95% CI: 1.27, 3.18]), as assessed with a 0 to 10 visual analogue scale, and shoulder function (standardised mean difference = 1.09 [95% CI: 0.61, 1.57]) as assessed with shoulder function scores. Although more adverse events (all mild) were reported with landmark-guided injections, the difference was not statistically significant (risk ratio = 0.20 [95% CI: 0.04, 1.13]).This review was only based on two moderate-sized trials. Blinding of patients was not performed in both trials, causing some risk of bias in outcome assessment since primary endpoints were wholly or partially patient-reported. There is a paucity of RCTs on image-guided versus landmark-guided corticosteroid shoulder injections examining pain, function and adverse events. In this review, patients who underwent image-guided (ultrasound) injections had statistically significant greater improvement in shoulder pain and function at 6 weeks after injection. Image-guided (ultrasound) corticosteroid injections potentially offer a significantly greater clinical improvement over blind (landmark-guided) injections in adults with shoulder pain. However, this apparent benefit requires confirmation from further studies (adequately-powered and well-executed RCTs).


Cutaneous infection with Mycobacterium fortuitum after localized microinjections (mesotherapy) treated successfully with a triple drug regimen.
Mesotherapy is a treatment method devised for controlling pain syndromes or diseases by subcutaneous microinjections given at or around the involved areas at short intervals of time. Different adverse effects have been described due to this modality of treatment. This report describes 3 patients with cutaneous infection caused by Mycobacterium fortuitum after mesotherapy. Three women, aged 24, 27 and 44 years, presented with similar clinical features, consisting of painful nodules located at the points where mesotherapy had been applied. A smear from a skin biopsy revealed the presence of acid-fast bacilli in all 3 cases. The specimen was cultured and eventually identified as M. fortuitum. A multidrug long-term regimen (combinations of 3 drugs from the following: ciprofloxacin, cotrimoxazole, clarithromycin and amoxicillin-clavulanic acid) was needed to achieve resolution of the lesions. After 15, 25 and 26 months of follow-up, no patient relapsed. Mycobacterium fortuitum is a rapidly growing mycobacterium that can lead to cutaneous infection after minor surgical procedures when aseptic measures are not adequate. Multiple drugs for several months are usually needed to treat this disease successfully.


Doxazosin in 'resistant' hypertension.
A study of doxazosin added to baseline therapy with a beta-adrenoceptor blocker plus a diuretic in the treatment of patients 'resistant' to the baseline therapy, showed that it was effective and generally well tolerated. The study was, however, open-label and lacked comparison with other third-line drugs.


Pentacyclic Triterpenoids from Sabia discolor Dunn and Their α-Glycosidase Inhibitory Activities.
Four new pentacyclic triterpenoids named Sabiadiscolor A-D (1 and 7-9) together with eleven known ones were isolated by repeated column chromatography. Their structures were identified and characterized by NMR and MS spectral data as 6 oleanane-type pentacyclic triterpenoids (1-6), 7 ursane-type ones (7-13), and 2 lupanane-type ones (14-15). Except for compound 15, all other compounds were isolated from Sabia discolor Dunn for the first time. Their α-glycosidase inhibitory activities were evaluated, which showed that compounds 1, 3, 8, 9, 13, and 15 implied remarkable activities with IC50 values ranging from 0.09 to 0.27 μM, and the preliminary structure-activity relationship was discussed.


A multivariate analysis of prognostic factors in adult Hodgkin's disease.
A multivariate analysis of the prognostic factors was carried out with a Cox model on 167 patients with Stage I-IV Hodgkin's disease. The following indicators were prospectively registered: Sex, age, clinical stage, systemic symptoms, histological type, number of involved areas, nodal size, mediastinal thoracic ratio (MTR), localization of mediastinal involvement according to the aortic arcus, hilar involvement, extent of radiotherapy, and extent and mode of chemotherapy. A linear logistic analysis showed that most of the indicators were interrelated. This emphasizes the necessity of a multivariate analysis in order to assess the independent influence of each of them. The three main prognostic indicators for complete remission achievement were age, clinical stage and involvement of lung hili. The three main prognostic indicators for disease-free survival were sex, size of mediastinal involvement (MTR) and use of alternating chemotherapy COPP/ABVD in the initial treatment strategy. The most important prognostic factor for survival was clinical stage followed by hilar involvement, age, and nodal size. The coefficients estimated by Cox regression analysis can be used to combine the important prognostic factors into a single index for each patient at presentation. The prognostic index for each patient would allow the identification of cases with poor prognosis who might benefit from additional initial treatment.


Association of healthcare worker behaviors with coronavirus disease 2019 (COVID-19) risk during four pandemic periods and characteristics associated with high-risk behaviors.
In a large healthcare worker cohort, we quantified the association between behaviors and risk of coronavirus disease 2019 (COVID-19) during different pandemic phases, adjusting for prior infection and vaccination. Individual characteristics, including personal concerns, were associated with these behaviors. Public health messaging should target high-risk populations and behaviors as the pandemic evolves.


Improved micromethod for mezlocillin quantitation in serum and urine by high-pressure liquid chromatography.
A rapid, sensitive, and specific method of analysis for mezlocillin in serum and urine by high-pressure liquid chromatography is described. A solid-phase extraction column was used to remove interfering substances from samples before chromatography. Quantitation included the use of an internal standard, nafcillin. Mezlocillin was chromatographed with a phosphate buffer-acetonitrile (73:27) mobile phase and a C-18 reverse-phase column and detected at a wavelength of 220 nm. The assay had a sensitivity of 1.6 micrograms/ml and a linearity of up to 600 micrograms/ml and 16 mg/ml in serum and urine, respectively, with only 0.1 ml of sample. The interday and intraday coefficients of variation for replicate analyses of spiked serum and urine specimens were less than 6.5%.


Ethics and the comprehensive application of epistemology in medical practice.
Our simple definition of ethics is good thought, speak and action. Epistemology means the hypothesis of facts about thought, speech and action. Medical practice is all means of medicine. Medicine classifies people into normal and abnormal. The abnormal are the sick. They loose some organs or those normal looking organs are dysfunctional. They are social problems, some can be treated, and some do not get the appropriate care. The problems of society of normal people are overeating and obesity, abortion, drug abuse, promiscuity, torture, terrorism, disobeying rules and order, corruption, brain-washing and unethical advertisements, etc. On the other hand, the social problems of the abnormal are down, deafness, blindness, dumb, hypertension, hypercholesterolemia, diabetes mellitus and cancer, etc. An example of the social-doctor problem is the mal distribution of doctors in rural areas. It was reported by the ministry of public health that the ratio of doctor to population to be 1:800 in Bangkok and 1:5, 700 in some rural areas in the north eastern part of Thailand. The doctors, themselves, are at a high grade of worker and intelligent quotient. They know all the problem and, at the same time, create problems, both, faster than the general population can do. It affects good and bad in the society. In the past, present and the foreseeable future the medical students get their studies in the western style. Their medical schools are situated in big cities. These schools are old and famous. They learn their medical procedure in a big hospital of more than 400 beds in the inpatient department wards. Their instructors and professors are highly qualified, are middle class people and well accepted in the society. Their families are lovely and warm. Their children study in the first class schools in town. The medical students feel very happy and appreciate seeing their professors in television routinely at prime time. In conclusion, their professors are an example of role model for them to follow. Everyone looks for security in her/his profession. Facts need no proof and reference. People with justice in mind should believe and understand the above mentioned. This leads to the problem of mal distribution of doctors in rural areas, why do doctors live in big cities or wish to be in the private sector? In fact, not many a number of doctors serve in the rural area. About 4-5 of them, their name will be announced yearly as the best rural doctor award. After the big ceremony, lasted not longer than a month, it is hard to remember their name. They are proud to be praised, it pushes them into stress intentionally with all the best of their intelligence and the total of their body strength to work harder in rural. Unfortunately their earning, the security of their profession, the increased chance of being sued, to get caught in the medical litigation, the expenses of their family social status and the study of their children cannot be compared to of those doctors in big city and/or in the private sector. Mal distribution of doctors in remote rural areas has been a persisting unresolved problem in many parts of the world, why not apply the principles of ethics and epistemology? They have been left, untouched forever.


[Use of vacuum-assisted closure in the topical treatment of surgical site infections].
This study was designed to evaluate the results of vacuum-assisted closure in the topical treatment of surgical site infections. Vacuum therapy was performed in 17 patients (10 males, 7 females; mean age 60 + or - 20 years) using the VAC system (Vacuum-Assisted Closure, Kinetic Concept Inc) for the treatment of surgical site infections. Infective wounds were in the hip (n=6), crus (n=5), knee (n=3), sacrum (n=2), and hand (n=1). The causative organism for infections was gram-positive bacteria in 15 patients (88.2%), and six patients (35.3%) had nosocomial infections. The wounds were treated with a negative pressure of 100-125 mmHg applied continuously for the first two days, and then intermittently for the following days. The mean follow-up period was 11 + or - 6 months. The mean duration of vacuum therapy was 16 + or - 4 days and the mean length of hospitalization was 31 + or - 19 days. The patients underwent a mean number of three surgical procedures (range 1 to 6) before vacuum therapy. The mean amount of discharge from the wound was 500 + or - 150 ml. Tissue edema and discharge problems were resolved in all the wounds and a hygienic and dry-looking surgical site was attained. In 11 patients (64.7%), clinical and bacteriologic eradication of infections was achieved at the surgical site through antibiotic use and vacuum therapy. Six patients with nosocomial infections continued to receive antibiotic treatment following resolution of surgical site problems. The mean wound area showed a significant reduction from 36 + or - 14 cm(2) to 11 + or - 10 cm(2) following vacuum therapy (p<0.05). Only two patients (11.8%) required further surgical interventions for the closure of wound site. Two patients (11.8%) complained of pain associated with vacuum application. Besides its topical advantages in the care of infected wounds, vacuum-assisted closure provides a more rapid and comfortable treatment opportunity, representing a reliable alternative to conventional wound care methods.


Fast Learning Radiance Fields by Shooting Much Fewer Rays.
Learning radiance fields has shown remarkable results for novel view synthesis. The learning procedure usually costs lots of time, which motivates the latest methods to speed up the learning procedure by learning without neural networks or using more efficient data structures. However, these specially designed approaches do not work for most of radiance fields based methods. To resolve this issue, we introduce a general strategy to speed up the learning procedure for almost all radiance fields based methods. Our key idea is to reduce the redundancy by shooting much fewer rays in the multi-view volume rendering procedure which is the base for almost all radiance fields based methods. We find that shooting rays at pixels with dramatic color change not only significantly reduces the training burden but also barely affects the accuracy of the learned radiance fields. In addition, we also adaptively subdivide each view into a quadtree according to the average rendering error in each node in the tree, which makes us dynamically shoot more rays in more complex regions with larger rendering error. We evaluate our method with different radiance fields based methods under the widely used benchmarks. Experimental results show that our method achieves comparable accuracy to the state-of-the-art with much faster training.


Raman spectroscopy: feasibility of in vivo survey of stratum corneum lipids, effect of natural aging.
The main function of the stratum corneum (SC) is for protection against external aggression. This is described as the barrier function. It mainly depends on the presence of a lipid matrix composed of ceramides, free fatty acids, cholesterol and its derivatives in the intercellular spaces. Previous studies have reported the application of Raman spectroscopy to reveal the organization of SC lipids and the state of their barrier functions. Several spectral features are directly informative about the lateral packing and the conformational order. In this work, in vivo Raman spectroscopy is used to asses the state of the SC lipid content and thus its barrier function, directly on the skin. To study the effect of natural aging on the organization of these lipids, spectra were collected from the internal side of the forearms of twenty volunteers aged from 22 to 64. Multivariate data processing enabled separation of the in vivo spectra according to the volunteers' ages. Spectral signatures show small variations, indicating a slight change in the lateral packing of SC lipids with aging of the skin.


Antihypertensive Teach-Back to Reduce Delays, Cancellations, and Interventions in a Freestanding Gastroenterology Clinic.
The purpose of this study was improving patient compliance with the 2014 American College of Cardiologists/American Heart Association Joint Task Force Clinical Practice Guidelines recommendation regarding continuation of antihypertensive medications throughout the perioperative period. A patient education initiative, using the teach-back method of instruction, was implemented and evaluated. Effectiveness of instruction was measured by tracking hypertension requiring pharmacological intervention, procedure delay, and procedure cancellation. Pre- and postintervention data were collected from electronic health records using a retrospective cohort design. A χ 2 analysis compared pre- and postintervention groups. The p value was calculated using the χ 2 analysis, (χ 2 [1, N = 1,044] = 7.71, p = .00548). No incidence of case delay or cancellation was experienced in either test group. Incidence of patients requiring preprocedural pharmacological intervention decreased by 70.5%. Statistically significant decreases in pharmacological treatment of hypertension supported permanent inclusion of the antihypertensive patient teaching method at the project gastroenterology clinic.


Nutrition, environment and physical performance of preschool children in Italy.
While overt malnutrition is known to interfere with several bodily functions and to cause a deterioration of the level of physical performance, little or no information is available on the effect of marginal nutrition on functional development, particularly at earlier ages. A cross-sectional study of the diet, somatic development and functional response to exercise of 2,241 children, aged 1-6 years, representing contrasting socioeconomic environments, has been carried out. The findings indicate that the upper socioeconomic urban child from Central Italy consumes a better diet and is larger than the underprivileged Southern child. While a greater proportion of the latter group experience a considerable degree of growth retardation, the better efficiency of their heart responses to exercise indicates that the level of nutrition of these children is still good enough to be compatible with a more satisfactory degree of physical fitness. The body fat content and skinfold thickness of the child from the Center have found to be significantly higher than those of the children from the poorer sections of the population, suggesting that at least part of the extra energy available to him for physical activity is being deposited as fat. This raises the question of the desirability of changes in somatic development characteristic of upward social mobility, when accompanied by increased adiposity without a proportional increase in the functional capacity.


The frequency of gonadotropin-releasing hormone stimulation determines the number of pituitary gonadotropin-releasing hormone receptors.
Gonadotropin-releasing hormone (GnRH) induces both synthesis and release of pituitary gonadotropins, but rapid or slow frequencies of stimulation result in reduced LH and FSH secretion. We determined the effects of frequency of GnRH stimulation on pituitary GnRH receptors (GnRH-R). Castrate male rats received testosterone implants (cast + T) to inhibit endogenous GnRH secretion. GnRH pulses were injected by a pump into a carotid cannula and animals received GnRH (25 ng/pulse) at various frequencies for 48 h. In control animals (saline pulses) GnRH-R was 307 +/- 21 fmol/mg protein (+/- SE) in cast + T and 598 +/- 28 in castrates. Maximum GnRH-R was produced by 30-min pulses and was similar to that seen in castrate controls. Faster or slower frequencies resulted in a smaller GnRH-R response and GnRH given every 240 min did not increase GnRH-R over saline controls. Equalization of the total GnRH dose/48 h (6.6 ng/pulse every 7.5 min or 200 ng/pulse every 240 min) did not increase receptors to the maximum concentrations seen after 30-min (25 ng) pulses. Serum LH responses after 48 h of injections were only present after 30-min pulses, and peak FSH values were also seen after this frequency. Serum LH was undetectable in most rats after other GnRH frequencies, even though GnRH-R was increased. These data show that GnRH pulse frequency is an important factor in the regulation of GnRH-R. A reduction of GnRH-R is part of the mechanism of down-regulation of LH secretion by fast or slow GnRH frequencies, but altered frequency also exerts effects on secretory mechanisms at a site distal to the GnRH receptor.


Leonurine protects middle cerebral artery occluded rats through antioxidant effect and regulation of mitochondrial function.
Oxidative stress is known to be involved in ischemic stroke. Intense interest is drawn to the therapeutic potential of Chinese herbs on ischemic stroke because many of them contain antioxidant properties. Leonurine, 1 of the active compounds from purified Herba Leonuri, was studied to evaluate its possible therapeutic effects on ischemic stroke. Method-Middle cerebral artery occlusion was selected as our model of study. The animals were pretreated with Leonurine orally for 7 days and the surgery was done. One day after surgery, 2,3,5-triphenyltetrazolium chloride staining and neurological deficit score were carried out to evaluate the functional outcome of animals, whereas levels of superoxide dismutase, glutathione peroxidase, and malondialdehyde were analyzed for oxidative stress analysis. For mitochondrial studies, 3 hours after surgery, mitochondria were isolated for analysis of reactive oxygen species production, adenosine triphosphate biosynthesis, oxygen consumption, and respiratory control ratio value. Result-In in vivo experiments, Leonurine pretreatment reduced infarct volume, improved neurological deficit in stroke groups, increased activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase, and decreased levels from the lipid peroxidation marker malondialdehyde. In terms of mitochondrial modulation, Leonurine inhibited mitochondrial reactive oxygen species production and adenosine triphosphate biosynthesis. Animal studies also demonstrated that the mitochondrial function and redox state were restored by Leonurine treatment. Leonurine has neuroprotective effects and carries a therapeutic potential of stroke prevention.


Swiss adolescents' and adults' perceptions of cannabis use: a qualitative study.
Few studies have attempted to investigate the nature of adolescents' and adults' conceptions and perceptions of cannabis use. Our objectives were to explore adolescent and adult perception of use and misuse of cannabis, and their opinions and beliefs about the current legal context and preventive strategies. We used focus group discussions with four categories of stakeholders: younger (12-15 year old) adolescents, older (16-19 year old) adolescents, parents of teenagers and professionals working with young people. In some areas (legal framework, role of the media, importance of early preventive interventions), we found consensual attitudes and beliefs across the four groups of participants. In all four groups, participants did not have any consensual vision of the risks of cannabis use or the definition of misuse. In the area of the prevention of cannabis use/misuse, while parents focused on the potential role of professionals and the media, thus minimizing their own educational and preventive role, professionals stressed the importance of parental control and education. Within the Swiss context, we conclude there exists an urgent need for information and clarification of the issues linked with cannabis use and misuse directed at parents and professionals.


Biotin-Thiamine-Responsive Basal Ganglia Disease in Children: A Treatable Neurometabolic Disorder.
Biotin-thiamine-responsive basal ganglia disease is a rare, autosomal recessive, treatable, neurometabolic disorder associated with biallelic pathogenic variations in the SLC19A3 gene. The condition may present as an early-childhood encephalopathy, an early-infantile lethal encephalopathy with lactic acidosis, with or without infantile spasms, or a late-onset Wernicke-like encephalopathy. The key radiological features are bilateral, symmetrical lesions in the caudate, putamen, and medial thalamus, with variable extension into the brain stem, cerebral cortex, and cerebellum. Treatment is life long and includes initiation of high dose biotin and thiamine. Genetic testing confirms the diagnosis. The prognosis depends on the time from diagnosis to the time of vitamin supplementation. The genotype-phenotype correlations are not clear yet, but the early infantile phenotype portends a poorer prognosis. We provide a brief overview of the disorder and emphasize the initiation of high-dose biotin and thiamine in infants and children with unexplained encephalopathy and basal ganglia involvement.


The clinical and radiological outcomes of multilevel posterior lumbar interbody fusion in the treatment of degenerative scoliosis: a consecutive case series with minimum 2 years follow up.
Surgical treatment for adult degenerative scoliosis (ADS) is a complex undertaking and is associated with a high complication rate. Our aim was to evaluate the clinical and radiological outcomes, mortality and morbidity of multilevel posterior lumbar interbody fusion (MPLIF) in the treatment in ADS based on the experience of a single tertiary referral center for spinal surgery. We performed a retrospective analysis of prospectively collected data of consecutive patients who had undergone multi-level posterior interbody fusion for degenerative scoliosis. We prospectively recorded patients' demographics, co-morbidities; coronal and sagittal plane deformity assessment and surgical details: number of instrumented levels, and intra-operative and postoperative complications. Functional outcomes and patient-reported complications were entered in our local spine surgery database (part of the Eurospine Spine Tango Registry) and used to collect data on functional scores and patient-reported complications preoperatively and at 6, 12 and 24 months' follow-up. Our study involved 13 males and 51 females with a mean age of 70.26 (range 49-90, SD 8.9). MPLIF was performed at five levels in one patient, four levels in 29 patients, three levels in 20 patients, and two levels in 14 patients. There were a total of 14 (21.87%) major, minor and mechanical complications. There were no procedure-related mortalities. The average COMI and Eq5d scores improved significantly post-surgery, and this improvement was maintained at a mean follow-up of up to two years. Multilevel posterior interbody fusion is a safe procedure, and in selected cases can result in good clinical and radiological outcomes with improvement in patient quality of life.


Racism as a clinical syndrome.
This paper examines the clinical effects of racism on its targets and, in particular, on its agents, the individuals who, wittingly or not, partake of the culture of racial privilege. It proposes a paradigm shift in regard to the clinical study of racism, and presents a structural model of racism, analogous to addiction as a disease, which holds that racism has an etiology and a clinical taxonomy that lends itself to differential diagnosis and treatment of those who manifest symptoms.


[Cardiac asthma after nifedipine and diltiazem].
The authors describe the case of a 57-year-old male patient with severe left ventricular dysfunction (ejection fraction of left ventricle--37%, left ventricular end diastolic pressure 32 mm Hg) as a result of an extensive anterior Q infarction of the heart muscle. The patient did not have signs of congestive heart failure. He was treated on account of angina pectoris on exertion, grade III according to NYHA, hypertension and diabetes. Nifedipine and diltiazem administration led to repeated attacks of cardiac asthma. Calcium channel blockers should be administered to patients with angina pectoris and severe left ventricular dysfunction only when nitrates alone do not eliminate ischaemia and pain. They should be administered carefully and with the knowledge that they may in rare instances cause clinical deterioration of left ventricular function.


Profiles of 800,000 users of the National Cancer Institute's Cancer Information Service since the debut of online assistance, 2003-2008.
In 2002, the Cancer Information Service (CIS) of the National Cancer Institute added to its toll-free telephone number 2 choices of media for access to cancer information specialists: e-mail and a proprietary online instant messaging service called LiveHelp. We sought to determine how new media users differ from telephone callers and the US population in general. During the 6 years since the new media were added, we collected data from more than 800,000 people who contacted CIS. Telephone calls to CIS declined while the number of LiveHelp and e-mail inquiries steadily increased. People who contacted CIS by telephone and LiveHelp were predominantly white and female and, compared with the general population, were relatively well educated. LiveHelp users were significantly younger, more educated, and more affluent than telephone callers. CIS clients asked most frequently for general cancer site information, information about treatment and side effects management, screening programs, and economic assistance. Telephone callers most often asked about breast cancer. The Internet has introduced new sources of health information and possibly a new type of health information seeker. With LiveHelp and e-mail, CIS is poised to meet the needs of the digital health consumer and also the traditional telephone caller.


Use of a Combined Blood-Glucose- and ß-Ketone-Measuring Device Improves Glycemic Control in Insulin-Treated Patients With Diabetes: The Gold Plus Study.
Using self-measurements of blood glucose (SMBG) is daily routine for patients with insulin-treated diabetes, however measuring ß-ketones in blood is not widespread. How the use of a combined device, which can measure both, is accepted in daily routine by patients and will lead to better glycemic control is not well studied. This multicenter, prospective, noninterventional study assessed the impact of routine use of the GlucoMen® LX Plus on patient acceptance, usage and glycemic control among insulin-treated patients with diabetes mellitus type 1 and type 2. A1c and self-reported frequency of SMBG were evaluated at baseline and also postprandial SMBG, ß-ketone measurements, and use of reminders after 3 and 6 months of use. A total of 631 patients, 254 type 1/350 type 2 (27 no type specified), with mean (SD) baseline A1c 8.5% (1.5), age 54.6 (15.6) years, and 47.3% female were studied. Frequent use of SMBG at baseline led to a higher decrease in A1c at 6 month (V3): -0.3% if SMBG measured up to 1/day versus -0.9% in 4-6/day. Increase of SMBG frequency during the study showed also a negative correlation to A1c, 9.2% at V1 versus 7.6% at V3. Postprandial SMBG was done by 77.7% and ß-ketone measurements by 45.5% of all patients; the reminders were used by 33.4% and led to an increased frequency of SMBG at 6 months. A combined device for SMBG and ß-ketone measurements is well accepted by patients with insulin-treated diabetes and can lead through the avoidance or detection of ketoacidosis/increased frequency of SMBG and increased awareness of the patients to an improved glycemic outcome.


The effectiveness of a group-based educational program on the self-efficacy and self-acceptance of menopausal women: A randomized controlled trial.
This study aimed to assess the effectiveness of a group-based educational training on the self-efficacy and self-acceptance of Iranian menopausal women using the PRECEDE-PROCEED model. This Randomized Controlled Trial (RCT) was conducted on 80 menopausal women in the age range of 47-55 years residing in the northeast of Iran. The participants were divided randomly into a test group (n = 40) and a control group (n = 40). We found that designing and implementation of a group-based educational training according to the PRECEDE-PROCEED model can significantly enhance the knowledge and performance of the test group with regard to self-efficacy and self-acceptance.


Localization of substance P- and enkephalin-like immunoreactivity in the human paravertebral sympathetic ganglia.
The presence of substance P- and enkephalin-like immunoreactive nerve fibers and terminals is demonstrated in the human paravertebral sympathetic ganglia by an indirect immunofluorescence technique. Substance P-positive nerve structures appear in the form of fiber bundles, isolated varicose filaments and dot-like and basket-like nerve terminals around the neuronal cell bodies. Their density shows a remarkable individual variability. Enkephalin-positive nerve structures appear as isolated varicose filaments and dot-like nerve terminals, forming densely innervated patchy areas. No substance P- or enkephalin-containing cell bodies were detected. No overlapping seems to exist among the areas innervated by the two types of neuropeptides.


Somatic development disorders of children with non specific inflammatory bowel diseases.
Frequency of inflammatory bowel diseases (Crohn's disease and ulcerative colitis) tends to increase in developing countries. Nearly 25% of cases affects pediatric patients. Inflammatory bowel diseases are often associated with weight loss and stunting in children. Moreover, weight and height deficiencies are often early symptoms. Initially, nonspecific or latent course of disease delays the diagnostic process. Malnutrition in inflammatory bowel diseases can be caused by disorders of digestion and nutrients' absorption, intestinal loss, increased energy expenditure and appetite impairment. Nutritional deficiencies and inflammatory agents lead to disturbance of tissue metabolism - muscle and bone - and retardation of somatic development of affected children. Thus, deficiencies of muscle mass, bone mineral density and body height are observed. Insufficient normalization of somatic features may be the consequence of recurrent nature of disease and specificity of pharmacological treatment. Present work deals with the current state of knowledge concerning the somatic development disorders of children with inflammatory bowel diseases. Abnormal nutritional status, bone mineral density deficits and growth failure of patients have been discussed in the context of their relations and dependencies on inflammatory, nutritional and therapeutic factors.


Metabolic pathways and intracellular trafficking of gangliosides.
Gangliosides constitute a large and heterogeneous family of acidic glycosphingolipids that contain one or more sialic acid residues and are expressed in nearly all vertebrate cells. Their de novo synthesis starts at the endoplasmic reticulum and is continued by a combination of glycosyltransferase activities at the Golgi complex, followed by vesicular delivery to the plasma membrane. At the cell surface, gangliosides participate in a variety of physiological as well as pathological processes. The cloning of genes for most of the glycosyltransferases responsible for ganglioside biosynthesis has produced a better understanding of the cellular and molecular basis of the ganglioside metabolism. In addition, the ability to delete groups of glycosphingolipid structures in mice has been enormously important in determining their physiological roles. Recently, a number of enzymes for ganglioside anabolism and catabolism have been shown to be associated with the plasma membrane, which might contribute to modulate local glycolipid composition, and consequently, the cell function.


The Effect of Mesenchymal Stem Cells on the Expression of IDO and Qa2 Molecules in Dendritic Cells.
Purpose: Mesenchymal stem cells (MSCs) have been shown to reduce the activity of immune cells, including dendritic cells (DCs). But the exact mechanism of mesenchymal inhibition of DCs is still unknown. In this study, the effect of mesenchymal cells on the expression of indoleamine dioxygenase (IDO) and Qa2 molecules in DCs was evaluated. Methods: MSCs and DCs were respectively isolated from the bone marrow and spleen of BALB/c mice. Then DCs were co-cultured with MSCs in the present and absence of lipopolysaccharides (LPS). Then the expression of mRNA and protein of IDO and Qa2 molecules were investigated in DCs that were treated with MSCs. Results: The expression of IDO and Qa2 mRNA in DCs that were treated with MSCs did not significantly differ from the control group. The expression of IDO protein in DCs that were cocultured with MSCs (in 1:10 and 1:50 ratios) in absence of LPS was increased, although they were not statistically significant (P values: 0.24 and 0.18, respectively). The expression of Qa2 protein in DCs that were co-cultured with MSCs (in 1:10 and 1:50 ratios) in presence of LPS was increased, although they were not statistically significant (P-values: 0.09 and 0.33, respectively). Conclusion: Our results denied the possibility that MSCs led to the induction of tolerogenic DCs by increasing the expression of the IDO and Qa2 immunomodulatory molecules.


Primary Leiomyosarcoma of Bone: Review and Update.
Leiomyosarcoma of bone is a rare primary osseous sarcoma characterized by smooth muscle differentiation and absence of malignant osteoid formation. Leiomyosarcoma of bone is diagnostically challenging; this can be improved with greater awareness of this entity and the ability to differentiate it from its histologic mimics. Because of its rarity, only a small number of studies are available in the literature. These factors contribute to our limited understanding of its pathology, prognosis, and treatment. To review the clinicopathologic features of leiomyosarcoma of bone and present the most up-to-date understanding of its behavior and management in accordance with the current literature. Review of pertinent literature on the major features, current knowledge thereof, and the authors' experience in the diagnosis and management of leiomyosarcoma of bone. Leiomyosarcoma of bone is a rare but well-recognized primary osseous sarcoma that may arise de novo or in association with radiation. Although it is diagnostically challenging, awareness of this rare sarcoma and knowledge of its key histomorphologic and immunohistochemical features allow for accurate diagnosis.