Changes in intravenous immunoglobulin prescribing patterns during a period of severe product shortages, 1995-2000.
Canadian consumption of intravenous immunoglobulin (IVIG) has increased dramatically since it was first marketed in the early 1980s, and Canada is now the world's largest per capita consumer. During the late 1990s, worldwide product shortages of IVIG occurred. This study was designed to identify the disease conditions for which IVIG was being prescribed in academic hospitals during this period, and to explore the effects that IVIG shortages had on prescribing patterns. Blood bank and pharmacy records of IVIG distribution were collected retrospectively from four Toronto teaching hospitals for the period 1995-2000. These records were then cross-referenced with patient medical records to determine the indication for IVIG administration. A total of 100,208 g of IVIG was prescribed to 429 patients over a 6-year period. Most of the IVIG consumption was in patients with haematological (22%) or neurological (20%) conditions, in recipients of bone marrow transplants (19%) and in patients with infectious disease-related conditions (including congenital and acquired hypogammoglobulinaemia, 18%). Dermatological conditions (7%) were the most rapidly growing indication for IVIG usage during the 6-year period of review, increasing from 0% of annual IVIG usage in 1995 to 16% in 2000. Over 80% of the diseases treated were supported by published recommendations. After 1997 there was an abrupt decline in the annual number of patients treated, primarily owing to a decline in single-use recipients. Annual consumption of IVIG, however, remained stable. IVIG shortages were followed by a decrease in the number of single-use recipients, who probably represented empirical use of IVIG; this had little effect on the total amount of IVIG distributed annually. Stricter adherence to currently available published recommendations may not be the optimal means of controlling IVIG use within an academic hospital setting. Rather, emphasis may be better placed on improving the evidence base upon which these recommendations are made, for example by conducting controlled prospective clinical trials.


The depressive effects of morphine on the C fibre response of dorsal horn neurones in the spinal rat pretreated or not by pCPA.
(1) The effects of morphine upon the transmission of nociceptive messages at the spinal level have been investigated in the spinal rat. The responses of dorsal horn cells induced by the activation of C fibres were depressed in all cases in a dose-dependent fashion, this effect being reversed by the opiate antagonist naloxone. An estimation of the ED50 at the cellular level leads to the value of 6.3 mg/kg. The responses to A delta fibres were also depressed dose-dependently whereas the responses to A alpha fibres were unaffected. This is a confirmation in the rat of the differential effects of morphine on responses of convergent units elicited by the stimulation of different fibres, as previously described in the cat. (2) The hypothesis of the participation of serotonergic terminals in these effects has been checked by comparing the preceding results to those obtained in pCPA pretreated animals. Two populations of units were observed in the latter group: two-thirds of cells showed a dose-response curve similar to that of the non-pretreated group whereas the remaining one-third were unaffected either by morphine or naloxone. It is concluded that, at least, two mechanisms are involved in the depressive effects of morphine at the spinal level, serotonergic terminals being implicated in one of these. (3) The lowering of spinal cord serotonin content was associated with a decrease of both the size of the excitatory receptive field (34%) and the activities related to C fibre input (36%) of the recorded dorsal horn cells. This result is discussed with reference to the excitatory or sensitizatory effect of serotonin upon chemoreceptors related to pain.


Trypanosomosis prevalence in natural field-based infection: insights into systematic review and meta-analysis of studies from 1980 to 2018 on The Gambian ruminants with special emphasis on cattle.
Consistent quantification of trypanosomes, the parasite responsible for African animal trypanosomosis, is important for effective surveillance, control, and eradication strategies. Here, we used a rigorously predefined protocol to search and select eligible publications that utilized either microscopy, serology, or molecular methods to investigate prevalence of trypanosomosis based on the presence of any of three most common Trypanosoma spp. (T. congolense, T. vivax, and T. brucei) in the field-based naturally grazed Gambian cattle, sheep, and goats. To combine results of studies on cattle through meta-analysis, sensitivity and subgroup analyses were carried out with the random effects model, and prevalence estimates of each study with 95% confidence intervals (CI) were presented with a forest plot. All the eligible studies utilized the buffy coat technique (BCT) to detect trypanosomes in the blood samples, while the more sensitive serological and molecular detection methods are yet to be widely exploited. Heterogeneity among the studies on cattle was moderate (I2 = 55%), and the pooled trypanosomosis prevalence based on the BCT was 5.2% (95% CI: 4.0-6.4). Meanwhile, estimated prevalence varied according to the trypanosome detection methods, study locations, types of publication, year, and length of observations. We could not pool the trypanosomosis prevalence in sheep and goats through meta-analysis due to small number of studies. The prevalence estimates based on the BCT ranged from 3.2 to 8.1% in goats and 2.8 to 10.6% in sheep. Even though there seems to be a slight decrease in trypanosomosis prevalence in cattle in one of the Gambian districts, there was no consistent trend across the years. It is thought that the literature search and formatting procedures presented in this study contribute to doing systematic reviews on the investigated subject and can be adapted for similar cases.


Outcome of Copeland surface replacement shoulder arthroplasty.
We report the outcome of humeral head surface replacement hemiarthroplasty performed at our institution using the Copeland prosthesis. We followed 56 shoulders (52 patients) for a mean of 34.2 months (range, 24-63 months). Two were lost to follow-up, and there were six deaths unrelated to the shoulder surgery. Preoperative diagnoses in the remainder were osteoarthritis (20), rheumatoid arthritis (26), rotator cuff tear arthropathy (1), and post-traumatic arthrosis (1). The mean age was 68 years. Constant scores for the whole group improved from a mean preoperative score of 16.4 (range, 8-36) to 54.0 (range, 20-83) at last follow-up (P < .05). Three cases underwent subsequent arthroscopic subacromial decompression for impingement symptoms. One case required revision for aseptic loosening to a stemmed implant. Contained, nonprogressive osteolysis was seen in 2 cases. One periprosthetic humeral neck fracture was managed successfully nonoperatively. These results are comparable to those obtained with a modern stemmed hemiarthroplasty and are similar to Copeland's own series.


Effects of high irradiances on photosynthesis, growth and crassulacean acid metabolism in the epiphyteKalanchoö uniflora.
Kalanchoë uniflora was grown in the glasshouse with and without shading. Chlorophyll content, area/FW ratio and specific leaf area were higher in leaves of shaded as compared to unshaded plants. Light saturation curves and continuous gas exchange measurements showed that the apparent quantum yield and the light-saturated photosynthetic rate were higher in shaded plants. Shaded plants had lower "mesophyll resistances" than unshaded plants, indicating that the different photosynthetic capacities reflected different contents of ribulose biphosphate carboxylase-oxygenase. Highlight treatment of plants grown in the shade resulted in a decreased photosynthetic efficiency, showing that these plants were sensitive to photoinhibition. However, dry matter production was higher in unshaded than in shaded plants. Obviously the difference in irradiance between the two growth regimes did more than offset the differences in photosynthetic efficiency. Applying additional nutrients did not alter the effects of high PFDs. The results are discussed in respect to photosynthetic performence and plant distribution in the epiphytic habitat.


Snail Chirality: The Unwinding.
Most snails are coiled clockwise, but in some species rare genetic variants with reverse coiling occur. Now, a molecular determinant of coiling direction has been identified, the cytoskeletal regulator formin.


Stress management training as a prevention program for heavy social drinkers: cognitions, affect, drinking, and individual differences.
The effectiveness of cognitive-affective stress management training (SMT) as a drinking reduction program for heavy social drinking college students was investigated. The SMT package included muscle relaxation and meditation training, cognitive restructuring, and coping skill rehearsal during induced affect. Treated and control subjects rated the frequency and intensity of their anxiety, anger and depression and recorded their alcohol consumption on a daily basis over a 6-month period. SMT significantly reduced posttreatment daily anxiety ratings and was associated with changes in four of ten irrational beliefs and a shift toward more internal locus of control in treated subjects. Reduction in anxiety was no longer evident at the 2 1/2- and 5 1/2-month follow-ups. The men in the SMT group showed a significant decrease in daily drinking rates at posttreatment and at the 2 1/2-month follow-up, but drinking returned to baseline levels by 5 1/2 months for the group as a whole. However, significant improvement variance in daily moods and in drinking rates over all posttreatment periods was accounted for by individual difference variables in the trained subjects but not in the control group, suggesting that these cognitive, personality, and social support variables are associated with response to stress management training. Implications of these results for future prevention research are discussed.


The economics of elective cesarean section.
Four million deliveries occur annually in the United States, and obstetric care has traditionally constituted a substantial portion of medical costs for young women, as well as being a major source of uncompensated care. The economic implications of a large shift in the mode of delivery are potentially important. This article reviews the relevant economic issues surrounding elective cesarean section and cesarean section at maternal request, summarizes the methodological quality and results of current literature on the topic, and presents recommendations for further study.


Electrothermal debracketing: patient acceptance and effects on the dental pulp.
Adhesives bond ceramic brackets so effectively that their removal by mechanical forces can fracture the brackets and may damage the tooth surface. Electrothermal debracketers have been developed to facilitate removal; whether the heat generated will damage the underlying pulp is unclear. In our experiment, a prototype device with a high heat tip was used to remove brackets from premolars in patients. The following parameters were evaluated: (1) time required for removal, (2) patient acceptance, and (3) histologic effect on the pulp. Forty-eight experimental teeth planned for orthodontic extraction were bonded by a filled Bis-GMA composite resin and a monocrystalline sapphire bracket. After the chemically cured composite set, debracketing was performed according to the manufacturer's recommendations. Seventeen premolars were not etched or bracketed and served as controls. The interval between heat application and removal of the bracket was timed. Patients were questioned as to sensations during debracketing. Teeth were extracted at 5 to 7 or 28 to 32 days and histologically prepared. Pulps were evaluated for alterations. Brackets were removed in an average of 2.1 seconds, usually at the bracket/composite interface. Patient acceptance was generally positive. Pulpal necrosis was not observed but, in a number of specimens, slight inflammation and odontoblastic disruption occurred at both observation periods.


Enhanced fusion of myoblasts with myofibers for efficient gene delivery induced by a partially purified protein fraction from rat muscle extract.
The biggest challenge to gene therapy is how to efficiently deliver the desired therapeutic gene into a sufficient number of recipient cells to achieve significant clinical efficacy. Here, we identified a partially purified extract from rat muscle probably containing myoblast specific fusion factor(s) (MSF), which significantly enhanced fusion of donor myoblast with host muscle fibers. Once incorporated, the introduced genetic construct could instruct the machinery of the hybrid cells to express the desired protein(s). Rat satellite cells containing a plasmid carrying a marker bone morphogenetic protein-4 (BMP-4) coding sequence were used as foreign gene delivery vehicle. BrdU labeling of the MSF-pretreated satellite cells allowed tracing the fate of the genetically modified satellite cells in the host muscles. Immunohistochemistry using anti-BMP-4 antibody demonstrated the translation of the introduced gene construct. It was demonstrated that in the presence of MSF, numerous BrdU positive nuclei and the expression of BMP-4 polypeptides could be observed in host hybrid fibers, while in the control group using rat serum to replace MSF containing fraction, only a few BrdU positive signals were detected. The expression of osteocalcin and the elevated alkaline phosphatase activity detected in the hybrid fibers indicated the proper folding, secretion and, post-translational modification of the expressed foreign protein. This strategy of enhanced myoblast-mediated gene transfer would break the major barrier in current practice of normal or engineered myoblast transplantation in the management of genetic muscle diseases or systemic genetic disorders.


Molecular tools for probing the microbiome.
The microbiome plays essential roles in health and disease. Our understanding of the imbalances that can arise in the microbiome and their consequences is held back by a lack of technologies that selectively knock out members of these microbial communities. Antibiotics and fecal transplants, the existing methods for manipulating the microbiota of the gastrointestinal tract, are not sufficiently pinpointed to reveal how particular microbial genes, strains, or species affect human health. A toolset for the precise manipulation of the microbiome could significantly advance disease diagnosis and treatment. Here, we provide an overview of current and future strategies for the development of molecular tools that can be used to probe the microbiome without producing off-target effects.


Mutational analysis of an ssi region carried by plasmid pACYC184.
To investigate the functional contribution of some structural components of the signal that directs single-stranded initiation of DNA replication (ssi signal) carried by a 119-nt segment of plasmid pACYC184 (Bahk et al., 1988), we constructed mutants carrying one-base substitutions and insertions using oligodeoxyribonucleotide (oligo) directed mutagenesis. Two one-base substitution mutants were obtained. The mutants, M13 delta lac 184/Sp and M13 delta lac 184/Ev, carried an SplI site and an EcoRV site, respectively, created by base substitution. Three kinds of synthetic oligos, that is, a 10-bp EcoRI linker, an 8-bp ScaI linker and an 8-bp SmaI linker, were inserted into the SplI site of M13 delta lac 184/Sp, and into the EcoRV site of M13 delta lac 184/Ev. The SSI activity of each mutant examined indicated that the one-base substitutions had different effects on the SSI functions of the altered ssi signals. This fact suggests that some structural components within the 119-bp region make distinct contributions to the SSI function. Moreover, when the three kinds of synthetic linkers were inserted into the mutants M13 delta lac 184/Sp and M13 delta lac 184/Ev, each of the insertion mutations affected the rate of conversion of ss DNA to RFI in vivo and the growth of the recombinant phages in a distinct manner. Judging from the above results, the base composition and the length of a certain specific site were crucial for maintenance of the SSI functional activity, and structural components of the ssi signal contributed distinctly to the SSI function.


Effect of pulsed estrogen therapy on hemostatic markers in comparison with oral estrogen regimen in postmenopausal women.
Hormone replacement therapy (HRT) is associated with an increased risk of thromboembolism dependent on the type of HRT; therefore, we compared therapy effects of intranasal with oral estrogens on coagulation and fibrinolysis markers in postmenopausal women. A randomized study in which 29 healthy hysterectomized women received intranasal 17beta-estradiol or oral estrogens for 3 months. There were no significant differences in the baseline characteristics between groups. Those women receiving intranasal estradiol showed a mild increment in plasminogen activator inhibitor-1 (PAI-I) (from 6.8 +/- 3.5 to 9.6 +/- 3.9 U/ml, p < 0.01); however, fibrinogen, factor VII-tissue factor complex (VIIa-rTF), antithrombin III (ATIII), protein C (PC) activity, protein S (PS) activity, plasminogen (PLG), and tissue-type plasminogen activator antigen (t-PA) were unchanged. In contrast, oral unopposed estrogens elevated t-PA (from 4.9 +/- 2.9 to 9.6 +/- 5.1 ng/ml, p < 0.01) in parallel with a decrement in PAI-I (from 5.2 +/- 4.0 to 2.7 +/- 1.7 U/ml, p < 0.05) and VIIa-rTF (from 201.2 +/- 181.0 to 140.6 +/- 108.7 mU/ml, p < 0.05). Fibrinogen, ATIII, PC, PS, and PLG were unchanged. Nasal 17beta-estradiol had no effect on the coagulation markers, except a moderate increment in PAI-1. In contrast, oral estrogens elicited a decrement in both VIIa-rTF and PAI-1; however, those changes did not surpass normal limits.


Portal Venous Flow Is Increased by Jejunal but Not Colonic Hydrogen Sulfide in a Nitric Oxide-Dependent Fashion in Rats.
Hydrogen sulfide (H2S) is a recently discerned endogenous signaling molecule that modulates the vascular system. Endogenous hydrogen sulfide has been shown to dilate both the mesenteric and portal vasculature. Gut microbiome, via sulfur reducing bacteria, is another source of H2S production within the gut lumen; this source of H2S is primarily produced and detoxified in the colon under physiologic conditions. Nitric oxide (NO), a major endogenous vasodilator in the portal circulation, participates in H2S-induced vasodilation in some vascular beds. We hypothesize that jejunal but not colonic H2S increases portal vein flow in a NO-dependent fashion. To evaluate the effects of luminal H2S, venous blood flow, portal venous pressure, and systemic venous pressure were measured in rats after administration of either vehicle or an H2S donor (NaHS) into the jejunum or the colon. We found that portal venous pressure and systemic pressure did not change and were similar between the three study groups. However, portal venous blood flow significantly increased following jejunal administration of NaHS but not in response to colonic NaHS or vehicle administration. To test the contribution of NO production to this response, another group of animals was treated with either an NO synthase inhibitor (N-Ω-nitro-L-arginine, L-NNA) or saline prior to jejunal NaHS infusion. After L-NNA pretreatment, NaHS caused a significant fall rather than increase in portal venous flow compared to saline pretreatment. These data demonstrate that H2S within the small intestine significantly increases portal venous blood flow in a NO-dependent fashion.


Drought-induced embolism in stems of sunflower: A comparison of in vivo micro-CT observations and destructive hydraulic measurements.
Vulnerability curves (VCs) are a useful tool to investigate the susceptibility of plants to drought-induced hydraulic failure, and several experimental techniques have been used for their measurement. The validity of the bench dehydration method coupled to hydraulic measurements, considered as a 'golden standard', has been recently questioned calling for its validation with non-destructive methods. We compared the VCs of a herbaceous crop plant (Helianthus annuus) obtained during whole-plant dehydration followed by i) hydraulic flow measurements in stem segments (classical destructive method) or by ii) in vivo micro-CT observations of stem xylem conduits in intact plants. The interpolated P50 values (xylem water potential inducing 50% loss of hydraulic conductance) were -1.74 MPa and -0.87 MPa for the hydraulic and the micro-CT VC, respectively. Interpolated P20 values were similar, while P50 and P80 were significantly different, as evidenced by non-overlapping 95% confidence intervals. Our results did not support the tension-cutting artefact, as no overestimation of vulnerability was observed when comparing the hydraulic VC to that obtained with in vivo imaging. After one scan, 25% of plants showed signs of x-ray induced damage, while three successive scans caused the formation of a circular brownish scar in all tested plants. Our results support the validity of hydraulic measurements of samples excised under tension provided standard sampling and handling protocols are followed, but also show that caution is needed when investigating vital plant processes with x-ray imaging.


Chemical-mineralogical characterization of C&D waste recycled aggregates from São Paulo, Brazil.
This study presents a methodology for the characterization of construction and demolition (C&D) waste recycled aggregates based on a combination of analytical techniques (X-ray fluorescence (XRF), soluble ions, semi-quantitative X-ray diffraction (XRD), thermogravimetric analysis (TGA-DTG) and hydrochloric acid (HCl) selective dissolution). These combined analytical techniques allow for the estimation of the amount of cement paste, its most important hydrated and carbonated phases, as well as the amount of clay and micas. Details of the methodology are presented here and the results of three representative C&D samples taken from the São Paulo region in Brazil are discussed. Chemical compositions of mixed C&D aggregate samples have mostly been influenced by particle size rather than the visual classification of C&D into red or grey and geographical origin. The amount of measured soluble salts in C&D aggregates (0.15-25.4mm) is lower than the usual limits for mortar and concrete production. The content of porous cement paste in the C&D aggregates is around 19.3% (w/w). However, this content is significantly lower than the 43% detected for the C&D powders (<0.15 mm). The clay content of the powders was also high, potentially resulting from soil intermixed with the C&D waste, as well as poorly burnt red ceramic. Since only about 50% of the measured CaO is combined with CO(2), the powders have potential use as raw materials for the cement industry.


Granulomatous appendicitis in a 12-year-old boy.
Isolated granulomatous inflammation of the appendix is extremely rare, and its etiology is still unknown. We describe a 12-year-old boy with isolated granulomatous appendicitis where the etiology could not be clarified despite infectious criteria such as high fever and gastroenteritis. Children with epithelioid granulomatous appendicitis have a good prognosis following appendectomy.


A case report: Catatonic symptoms secondary to systemic lupus erythematosus with multiple infections: neuropsychiatric or "mimickers?"
Systemic lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric (NP) manifestations. However, typical symptoms of catatonia are uncommon. Neuropsychiatric SLE or its "mimickers" may cause NP symptoms, making differential diagnosis a significant challenge in clinical practice. A 68-year-old female with SLE was hospitalized for edema, lung infection, and recurrent fungal mouth ulcers after multiple courses of cortisol and immunosuppressive therapy. Five days after admission, stupor, immobility, mutism, and rigidity were observed. "Mimickers": catatonic disorder due to a general medical condition. Initially, relevant laboratory tests, imaging studies, and the disease activity index score were performed. A survey of the causes of the disease was conducted among the patient's relatives. Subsequently, we discontinued moxifloxacin, corticosteroids, fluconazole, and other medications and inserted a gastric tube for nutritional support. During this process, traditional Chinese medicine and acupuncture have been utilized. After 3 days, the patient recovered and only complained of fatigue. When SLE presents with NP symptoms, it is essential to make a correct diagnosis in order to guide appropriate treatment by actively searching for inducers and clinical, laboratory, and neuroradiological characteristics that can aid in the differential diagnosis. When treatment options are limited, it can be beneficial to try a variety of combination strategies, such as traditional Chinese medicine and acupuncture.


Molecular identification and characterization of prohibitin from Echinococcus granulosus.
Prohibitin (PHB) is a widely distributed protein that functions as a molecular chaperone, is involved in the regulation of cell cycle, and maintains mitochondrial structure and functions of the anti-apoptosis, senescence, and proliferation. The aim of this study was to characterize PHB in Echinococcus granulosus (EgPHB), a harmful cestode parasite of humans, many livestock species, and wild animals. We found that EgPHB is a conserved SPFH (stomatin, prohibitin, flotillin, and HflK/C) domain-containing protein, consisting of 289 amino acids, which shares 42.66-99.31% identity with PHBs from other parasites and mammals. EgPHB was located mainly in the tegument issue of protoscoleces, in the inner body of adult worms, and was expressed widely in the germinal layer. This is the first report on prohibitin from E. granulosus, and EgPHB is considered to be a valuable protein to study more in the future.


The impact of scapular notching on reverse shoulder glenoid fixation.
Scapular notching is a well-documented complication of reverse shoulder arthroplasty. The effect of scapular notching on glenoid fixation is unknown. This study dynamically evaluated reverse shoulder glenoid baseplate fixation and assessed the effect of scapular notching on fixation in composite scapulae. A cyclic test was conducted to simulate 55° of humeral abduction in the scapular plane as a 750-N axial load was continuously applied to induce a variable shear and compressive load. Before and after cyclic loading, a displacement test was conducted to measure glenoid baseplate displacement in the directions of the applied static shear and compressive loads. For the scapulae without a scapular notch, glenoid baseplate displacement did not exceed the generally accepted 150-μm threshold for osseous integration before or after cyclic loading in any component tested. For the scapulae with a scapular notch, glenoid baseplate displacement exceeded 150 μm in 2 of the 7 samples before cyclic loading and in 3 of the 7 samples after cyclic loading. The average pre-cyclic glenoid baseplate displacement in the direction of the shear load was significantly greater in scapulae with a scapular notch than those without a scapular notch both before (P = .003) and after (P = .023) cyclic loading. Adequate glenoid baseplate fixation was achievable in most cases in scapulae with a severe scapular notch; however, the fact that this micromotion threshold was not met in all scapulae with a notch is concerning and implies that severe notching may play a role in initial glenoid baseplate stability.


Integration of metabolomic and transcriptomic profiles to identify biomarkers in serum of lung cancer.
We used blood serum samples collected from 31 lung cancer (LC) patients and 29 healthy volunteers in this study. Levels of serum metabolites were qualitative quantified with gas chromatography-mass spectrometry (GC-MS), and the data were analyzed by partial least-squares discrimination analysis (PLS-DA). Based on the Kyoto Encyclopedia of Genes and Genomes database, we performed pathway-based analysis utilizing metabolites presented at differential abundance between the LC serum samples and the normal healthy serum samples for systematical investigation on the metabolic alterations associated with LC pathogenesis. Finally, we analyzed the significantly enriched pathways as well as their relevant differentially expressed messenger RNAs, and drawn a correlation network plot to identify the serum metabolic biomarkers and the significantly altered metabolic pathways for LC. GC-MS analysis showed that 23 of the 169 metabolites identified were significantly different. PLS-DA model revealed that 13 of these metabolites were with variable importance > 1, and particularly five were with area under curve > 0.9. Pathway-based analysis demonstrated that five of eight enriched metabolic pathways were statistically significant with false discovery rate < 0.05. Lastly, the correlation networks between these pathways and their related genes suggested that 29 genes had correlation degree > 10, which were mainly engaged in the purine metabolism. In conclusion, we identified indole-3-lactate, erythritol, adenosine-5-phosphate, paracetamol and threitol as serum metabolic biomarkers for LC through metabolomics analysis. Besides, we identified the purine metabolism as the significantly altered metabolic pathway in LC with the help of transcriptomics analysis.


The developmental-clinical rationale for the use of seclusion in the psychiatric treatment of children.
The use of seclusion as an element in a therapeutic management model for ego-deficient children is presented, based on what is known about the normal socialization process and the ego deficits of some psychiatrically hospitalized children. A distinction is made between retaliatory punishment and supportive control techniques. Specific recommendations for the implementation of seclusion in a nurturing environment are made.


Formation of hydroxanthommatin-derived radical in the oxidation of 3-hydroxykynurenine.
Using ESR, a radical (g = 2.004) was detected in the reaction mixture of 3-hydroxykynurenine (3-HKY), H2O2, and horseradish peroxidase. The radical was stable and was detected even after 5 h. On HPLC analysis of the reaction mixture, two radical peaks (Peak-1 and Peak-2) were detected using ESR. The ESR spectra of Peak-1 and Peak-2 radicals were the same and identical with that of the original radical in the reaction mixture. The retention times of Peak-1 and Peak-2 corresponded to those of authentic xanthommatin (XA) and hydroxanthommatin (Hydro-XA), respectively, XA being formed in the oxidation of 3-HKY by potassium ferricyanide and Hydro-XA being formed in the reduction of XA by sodium metabisulfite. The absorbance spectra of Peak-1 and Peak-2 were nearly identical with those of authentic XA and Hydro-XA. The absorbance spectrum of Peak-2 changed from that of Hydro-XA to that of XA, indicating that Hydro-XA auto-oxidized to XA in the air. The ESR signal intensity of the Peak-2 radical developed in accordance with the progress of this auto-oxidation of Hydro-XA to XA. It was supposed that the Peak-2 radical was generated in the auto-oxidation of Hydro-XA after its elution from the HPLC column. Thus, the radical seemed to be the one-electron oxidized form of Hydro-XA. The Peak-1 radical appeared to be the true retention of the radical on the column and to be eluted with a much larger amount of XA. The separation of the radical from XA was impossible on the column. Hemoglobin (Hb) or hematin also induced the same radical in the reaction mixture of 3-KHY, H2O2, and Hb or hematin.


Interleukin-1 receptor type-1 in non-hematopoietic cells is the target for the pro-atherogenic effects of interleukin-1 in apoE-deficient mice.
Interleukin (IL)-1 produced by vascular and bone marrow-derived cells exerts proinflammatory effects in these cell types by binding to IL-1 receptor type-1 (IL-1R1). We have previously shown that bone marrow-derived IL-1α and IL-1β are critical for atherogenesis in apoE knockout (KO) mice. The aim of the present study was to investigate whether IL-1R1 on vascular wall resident or bone marrow-derived cells mediates IL-1's effects in atherogenesis. We generated apoE-/-/IL-1R1-/- double knockout (DKO) mice and created radiation chimeras. Aortic sinus lesion area was 20-47% lower in DKO compared to apoE KO mice with similar plasma lipids. The production of IL-1α and IL-1β upon stimulation with LPS was not altered in IL-1R1-/- compared to IL-1R1+/+ peritoneal macrophages. DKO mice transplanted with IL-1R1+/+ bone marrow-derived cells had reduced (48%) aortic sinus lesion compared to apoE KO mice while specific deficiency of IL-1R1 in bone marrow-derived cells did not attenuate atherosclerosis. The mRNA levels of genes that promote macrophage recruitment to the vascular wall, namely CD68, VCAM-1, ICAM-1 and MCP-1 were lower in aortas from DKO compared to apoE KO mice. Finally, blockade of IL-1R1 with IL-1R antagonist (IL-1Ra) resulted in complete abrogation of IL-1β-induced expression of adhesion and chemotactic molecules and IL-1α, in isolated human umbilical vein endothelial cells (HUVEC). Vascular wall resident cells are the main targets for the pro-atherogenic effects of bone marrow-derived IL-1 through IL-1R1, partly by induction of adhesion and chemotactic molecules in endothelial cells.


Spontaneous intramedullary hematoma initially mimicking myocardial infarction.
Spontaneous intramedullary hematoma (IMH) is a rare condition. The initial clinical manifestations are variable. Early symptoms of high thoracic IMH include thoracocervical pain that can be mistaken for emergent cardiopulmonary conditions such as myocardial infarction, pulmonary embolus, and aortic dissection. We report on a 34-year-old man who presented initially with chest pain and radiating pain in both shoulders. He was initially misdiagnosed as having a myocardial infarction and treated with heparin. Two hours after admission, correct diagnosis of IMH was based on the repeated neurologic examination and spine magnetic resonance imaging study. The patient underwent emergency surgical decompression and hematoma removal.We draw the misdiagnosis to the attention of the emergency physicians because early recognition of spontaneous IMH is very important for early surgical decompression to improve the prognosis.


Structure of the glycoprotein Ib.IX complex from platelet membranes.
The glycoprotein Ib.IX complex is a major component of the platelet membrane. It mediates the adhesion of platelets to exposed subendothelium and provides an attachment site for the membrane skeleton on the plasma membrane. The present study was designed to characterize the structure of the glycoprotein Ib.IX complex. Electron microscopy of purified glycoprotein Ib.IX complex in detergent showed that each complex existed as a flexible rod with a globular domain on either end. The overall length of the complex was approximately 59.5 nm. The smaller globular domain had a diameter of approximately 8.9 nm; the larger, a diameter of approximately 15.9 nm. In the absence of detergent, the glycoprotein Ib.IX complexes tended to self-associate through the larger globular domain, suggesting that this domain contained the hydrophobic region that inserts into the membrane. Proteases known to cleave glycoprotein Ib alpha close to its membrane-insertion site released the larger globular domain. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that this domain was composed of glycoprotein Ib beta, glycoprotein IX, and a Mr = 25,000 fragment of glycoprotein Ib alpha. Proteolysis at the external end of glycoprotein Ib alpha reduced the size of the smaller globular domain. This study shows that the glycoprotein Ib.IX complex has an elongated shape, with a globular domain on the end that inserts into the membrane and a smaller globular domain on the end of glycoprotein Ib alpha that is oriented external to the plasma membrane.


[Diagnostic contribution of HBME-1 and anti-cytokeratin-19 antibodies in thyroid pathology: a retrospective study of 163 cases].
The objective of our study was to estimate the expression of 2 antibodies HBME-1 and anti-cytokeratin-19 and their diagnostic importance in thyroid pathology. 163 thyroid lesions were retrospectively examined by immnohistochemistry. 92% (46/50 cases) of papillary carcinomas expressed HBME-1 as well as 50% (8/16 cases) of follicular carcinomas and 15% (6/40 cases) of follicular adenomas. 8 insular carcinomas, 5 anaplastic carcinomas, 20 cases of Basedow disease and lymphocytic thyroiditis, and the 24 cases of nodular goiters did not express it or very focally. Anti-cytokératine-19 marked 92% of papillary carcinomas, 56.2% of follicular carcinomas, 100% of the medullar carcinomas and 45% of follicular adenomas. Whereas the cases of anaplastic carcinomas, Basedow disease, thyroiditis and the cases of nodular goiters were negative or focally marked. HBME-1 is an excellent marker for papillary carcinoma which can be helpful in the diagnosis of its follicular variant; the association with anti-cytokératine-19 increases its specificity.


Osmoregulation and antioxidant production in maize under combined cadmium and arsenic stress.
An investigation was carried out to examine the combined and individual effects of cadmium (Cd) and arsenic (As) stress on osmolyte accumulation, antioxidant activities, and reactive oxygen species (ROS) production at different growth stages (45, 60, 75, 90 days after sowing (DAS)) of two maize cultivars viz., Dong Dan 80 and Run Nong 35. The Cd (100 μM) and As (200 μM) were applied separately as well as in combination (Cd + As) at 30 DAS. Results revealed pronounced variations in the behavior of antioxidants, osmolytes, and ROS in both maize cultivars under the influence of Cd and As stress. Activities of enzymatic (SOD, POD, CAT and APX, GPX, GR) and non-enzymatic (GSH and AsA) antioxidants, generation of ROS, and accumulation of osmolytes were enhanced with the passage of time; therefore, the maximum values for these attributes were observed at 90 DAS for both cultivars. Exposure of plants to Cd or As stress considerably enhanced the antioxidant activities, ROS, and osmolyte accumulation compared with control, while combined application of Cd + As was more devastating in reducing plant biomass of both maize cultivars. Among cultivars, Dong Dan 80 was better able to negate the heavy metal-induced oxidative damage, which was associated with higher antioxidant activities, greater osmolytes accumulation, and lower ROS production in this cultivar.


Community-associated Clostridium difficile infections, Monroe County, New York, USA.
We conducted active sentinel surveillance in Monroe County, New York, USA, to compare incidence of community-associated Clostridium difficile infections (CA-CDIs) with that of health care-associated infections (HA-CDIs) and identify exposure and strain type differences between CA and HA cases. Patients positive for C. difficile toxin and with no documented health care exposure in the previous 12 weeks were defined as possible CA case-patients. Patients with onset in a health care setting or recent health care exposure were defined as HA case-patients. Eighteen percent of CDIs were CA; 76% were in persons who reported antimicrobial drug use in the 12 weeks before CDI diagnosis. Strain type distribution was similar between CA and HA cases; North American pulsed-field 1 was the primary strain (31% CA, 42% HA; p = 0.34). CA-CDI is an emergent disease affecting patients recently exposed to antimicrobial drugs. Community strains are similar to those found in health care settings.


Attitudes of internal medicine physicians toward type 2 diabetes.
This study was designed to identify differences among internists in their attitudes about diabetes and how those attitudes influence practice behavior. A cross-sectional study of 55 internists in an academic medical center was done using the Diabetes Attitude Scale (DAS-3), a valid and reliable measure of attitudes toward diabetes. Most respondents were white (89%), male (65%), and < or = 40 years old (85%). On the need for special training, internists were significantly different from the standardized norm for the DAS-3. Similar differences were observed on the seriousness of type 2 diabetes, the value attached to "tight control," and patient autonomy. Differences by age, sex, and level of training were not significant. Regardless of age, sex, or level of training, internal medicine physicians have negative attitudes toward type 2 diabetes that require future educational interventions.


Robotic resection of a mediastinal parathyroid cyst.
Mediastinal parathyroid cysts (PC) are rare, benign lesions, reported in fewer than 150 cases worldwide. Although most are asymptomatic and discovered incidentally on imaging, symptoms of dyspnea, dysphagia, hoarseness, palpitations, hypercalcemia, and innominate or jugular venous thrombosis have been reported. Sternotomy or thoracotomy has traditionally been the approach used to resect mediastinal PCs. We describe the first reported case of a robot-assisted resection of a mediastinal PC.


How Can We Help a Patient With a Small Failing Bioprosthesis?: An In Vitro Case Study.
The aim of this study was to investigate the hemodynamic performance of a transcatheter heart valve (THV) deployed at different valve-in-valve positions in an in vitro model using a small surgical bioprosthesis. Patients at high surgical risk with failing 19-mm surgical aortic bioprostheses are not candidates for valve-in-valve transcatheter aortic valve replacement, because of risk for high transvalvular pressure gradients (TVPGs) and patient-prosthesis mismatch. A 19-mm stented aortic bioprosthesis was mounted into the aortic chamber of a pulse duplicator, and a 23-mm low-profile balloon-expandable THV was deployed (valve-in-valve) in 4 positions: normal (bottom of the THV stent aligned with the bottom of the surgical bioprosthesis sewing ring) and 3, 6, and 8 mm above the normal position. Under controlled hemodynamic status, the effect of these THV positions on valve performance (mean TVPG, geometric orifice area, and effective orifice area), thrombotic potential (sinus shear stress), and migration risk (pullout force and embolization flow rate) were assessed. Compared with normal implantation, a progressive reduction of mean TVPG was observed with each supra-annular THV position (normal: 33.10 mm Hg; 3 mm: 24.69 mm Hg; 6 mm: 19.16 mm Hg; and 8 mm: 12.98 mm Hg; p < 0.001). Simultaneously, we observed increases in geometric orifice area (normal: 0.83 cm(2); 8 mm: 1.60 cm(2); p < 0.001) and effective orifice area (normal: 0.80 cm(2); 8 mm: 1.28 cm(2); p < 0.001) and reductions in sinus shear stresses (normal: 153 dyne/cm(2); 8 mm: 40 dyne/cm(2); p < 0.001), pullout forces (normal: 1.55 N; 8 mm: 0.68 N; p < 0.05), and embolization flow rates (normal: 32.91 l/min; 8 mm: 26.06 l/min; p < 0.01). Supra-annular implantation of a THV in a small surgical bioprosthesis reduces mean TVPG but may increase the risk for leaflet thrombosis and valve migration. A 3- to 6-mm supra-annular deployment could be an optimal position in these cases.


The nature of the proteins of fat emboli released during total hip prosthesis.
Human fat emboli, released during total hip prosthesis contained less than 0.1 per cent proteins. Most likely, this was the result of absorption of the fat particle during in vitro procedures.


Aspects of the media and their relevance to bulimic attitudes and tendencies among female college students.
We examined whether media pressures would mediate the association between two dimensions of the media (source of information and internalization) and bulimic attitudes/tendencies. The study sample consisted of 106 female college students (M age=19.9; range=18-22). Participants completed anonymous, self-report measures on media influences on body image and appearance as well as disordered eating attitudes/behaviors. Findings showed that the association between two dimensions of the media (source of information and internalization) and bulimic attitudes/tendencies was mediated by perceived media pressures. Such findings highlight the significant influence of media pressures on bulimic attitudes/tendencies. Future research and prevention implications are discussed.


Quantitative ultrasound bone measurements in pre-pubertal children with type 1 diabetes.
This case-control study aimed to assess bone status in children with type 1 diabetes mellitus (T1DM). Fifty-seven pre-pubertal patients (37 boys, aged 7.9 ± 2.5 years, T1DM duration 3.1 ± 1.6 years) and 171 age-matched healthy controls (111 boys) were studied. Quantitative ultrasound (QUS) was used to measure amplitude dependent speed of sound (Ad-SoS) at hand phalanges (expressed as standard deviation score [SDS]). Anthropometric and disease-related data (including mean HbA(1c) from whole T1DM duration [T], last year [Y], examination day [D]) were collected. Mean Ad-SoS SDS in patients -0.13 ± 1.32 (95% confidence interval [CI] -0.48, 0.22) was similar to that of controls. Subgroups discriminated according to HbA(1c) D, Y and T (cut-off 7.0%) did not differ regarding analyzed parameters. In patients, Ad-SoS SDS was comparable for both genders. Multivariable stepwise regression analysis showed significant negative influence of diabetes duration on Ad-SoS SDS. QUS findings in pre-pubertal children with T1DM do not differ from those in healthy children. Disease duration seems to affect negatively Ad-SoS SDS. However, independent prospective studies are needed to elucidate the true associations.


Neurosurgery Elective for Preclinical Medical Students: Early Exposure and Changing Attitudes.
Exposure to surgical subspecialties is limited during the preclinical years of medical school. To offset this limitation, the authors created a neurosurgery elective for first- and second-year medical students. The objective was to provide each student with early exposure to neurosurgery by combining clinical experience with faculty discussions about the academic and personal realities of a career in neurosurgery. From 2012 to 2013, the authors offered a neurosurgery elective course to first- and second-year medical students. Each class consisted of the following: 1) peer-reviewed article analysis; 2) student presentation; 3) faculty academic lecture; 4) faculty personal lecture with question and answer period. Thirty-five students were enrolled over a 2-year period. After completing the elective, students were more likely to: consider neurosurgery as a future career (P < 0.0001), perceive the personalities of attending physicians to be more collegial and friendly (P = 0.0002), perceive attending quality of life to be higher (P < 0.0001), and believe it was achievable to be a neurosurgeon and have a family (P < 0.0001). The elective did not alter students' perceived difficulty of training (P = 0.7105). The neurosurgery elective course significantly increased student knowledge across several areas and changed perceptions about collegiality, quality of life, and family-work balance, while not altering the students' views about the difficulty of training. Adopting a neurosurgery elective geared towards preclinical medical students can significantly change attitudes about the field of neurosurgery and has potential to increase interest in pursuing a career in neurosurgery.


Intracellular formation of α-synuclein oligomers and the effect of heat shock protein 70 characterized by confocal single particle spectroscopy.
Synucleinopathies such as dementia with Lewy bodies or Parkinson's disease are characterized by intracellular deposition of pathologically aggregated α-synuclein. The details of the molecular pathogenesis of PD and especially the conditions that lead to intracellular aggregation of α-synuclein and the role of these aggregates in cell death remain unknown. In cell free in vitro systems considerable knowledge about the aggregation processes has been gathered. In comparison, the knowledge about these aggregation processes in cells is far behind. In cells α-synuclein aggregates can be toxic. However, the crucial particle species responsible for decisive steps in pathogenesis such as seeding a continuing aggregation process and triggering cell death remain to be identified. In order to understand the complex nature of intracellular α-synuclein aggregate formation, we analyzed fluorescent particles formed by venus and α-synuclein-venus fusion proteins and α-synuclein-hemi-venus fusion proteins derived from gently lyzed cells. With these techniques we were able to identify and characterize α-synuclein oligomers formed in cells. Especially the use of α-synuclein-hemi-venus fusion proteins enabled us to identify very small α-synuclein oligomers with high sensitivity. Furthermore, we were able to study the molecular effect of heat shock protein 70, which is known to inhibit α-synuclein aggregation in cells. Heat shock protein 70 does not only influence the size of α-synuclein oligomers, but also their quantity. In summary, this approach based on fluorescence single particle spectroscopy, that is suited for high throughput measurements, can be used to detect and characterize intracellularly formed α-synuclein aggregates and characterize the effect of molecules that interfere with α-synuclein aggregate formation.


Practical considerations for the routine application of left lateral Sims' position for vaginal delivery.
The lateral Sims' position was evaluated for routine use in vaginal deliveries. The study demonstrates that delivery in the lateral Sims' position is practical and easily mastered; most easily applied for spontaneous or uncomplicated outlet forceps delivery; of special advantage in breech deliveries, congestive heart failure, hip joint restriction, and leg varicosities; and well accepted by women looking for a less restricted and more natural delivery experience.


Clinicians' reasons for deviations from recommended dosing practices for antipsychotic medications.
This study was designed to investigate clinician rationales for prescribing higher than recommended dosages of antipsychotic medications in patients with schizophrenia. Prescribers for all patients at two VA medical centers whose dosage exceeded PORT recommendations were interviewed. For 91/107 (85%) of patients, the prescriber responded that the current dosage should not be decreased. Positive symptoms were the most common target symptoms (94%), followed by negative symptoms (26%), anxiety (23%), and insomnia (13%). In patients receiving higher than recommended dosages of antipsychotics, clinicians were frequently able to cite specific target symptoms.


The aquaporin-2 water channel in autosomal dominant primary nocturnal enuresis.
Nocturnal enuresis is one of the most common diagnoses in a pediatric clinic. Recently, linkage analysis revealed a 2-point lod score of 4.2 in 6 families with dominant primary nocturnal enuresis around the aquaporin-2 (AQP2) water channel locus. Since primary nocturnal enuresis is ameliorated by desmopressin, AQP2 expression is increased by desmopressin and AQP2 is essential for concentrating urine, we determined whether a mutation in the AQP2 gene could cause primary nocturnal enuresis in these families. Genomic DNAs of several patients from the 6 families were analyzed for disease causing mutations in the 4 exons of the AQP2 genes. In 1 family a G to A transition in the intron 1 splice donor site was found but it was also found in healthy subjects. In another family a C to T transition in the intron 1 splice acceptor region was identified but it was often found in splice acceptor sites. In 2 families a C to T transition was identified in the coding region of exon 3 but this mutation did not lead to a changed amino acid. Since no mutation in the AQP2 coding sequence was found, while this is essential for involvement in dominant primary nocturnal enuresis, the AQP2 gene is excluded as a candidate for autosomal dominant PNE in these families in which the disease co-segregates with chromosome 12q.


Triptolide inhibits angiogenesis in microvascular endothelial cells through regulation of miR-92a.
Atherosclerosis is one common chronic inflammatory disease in which angiogenesis is involved. Here we established an in vitro cell model of angiogenesis made by human dermal microvascular endothelial cells (HMEC-1) and work to investigate the role of triptolide (TPL) in this model. To induce angiogenesis, HMEC-1 cells were cultured in Matrigel-conditioned medium. The ratio of tubes to nucleus was detected. To evaluate angiogenesis, Western blot assay was carried out to detect endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor receptor-2 (VEGFR2) and VEGF. Cell counting kit-8 was utilized to estimate the viability of HMEC-1 cells. microRNA (miR)-92a was analyzed by qRT-PCR. The targeting relationship between integrin subunit alpha 5 (ITGA5) and miR-92a was verified through luciferase activity assay. The effects of ITGA5 on signaling transducers (ERK, PI3K, and AKT) in a phosphorylated form were valued using Western blot method. After stimulated by TPL, LY294002 and PD98059, the alteration in phosphorylation of the signaling transducers was evaluated by Western blot assay. The ratio of tubes to nucleus and angiogenesis related factors were increased with the delaying of culture time. TPL decreased the expression of angiogenesis factors. Furthermore, miR-92a was upregulated by TPL and miR-92a silence upregulated angiogenesis factors. In addition, TPL decreased ITGA5 which was proved as a target of miR-92a. ITGA5 overexpression resulted in the abundance of angiogenesis factors while ITGA5 silence led to the opposite results. Meanwhile, ITGA5 overexpression increased phosphorylation of ERK, PI3K and AKT while ITGA5 silence reversed the trend. TPL (as an anti-angiogenesis agent) suppressed angiogenesis by upregulating miR-92a, and miR-92a-mediated down-regulation of ITGA5 blocked the signaling transduction of ERK and PI3K/AKT pathways.


Self-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery.
While several COVID-19 vaccines have been in use, more effective and durable vaccines are needed to combat the ongoing COVID-19 pandemic. Here, we report highly immunogenic self-assembling SARS-CoV-2 spike-HBsAg nanoparticles displaying a six-proline-stabilized WA1 (wild type, WT) spike S6P on a HBsAg core. These S6P-HBsAgs bound diverse domain-specific SARS-CoV-2 monoclonal antibodies. In mice with and without a HBV pre-vaccination, DNA immunization with S6P-HBsAgs elicited significantly more potent and durable neutralizing antibody (nAb) responses against diverse SARS-CoV-2 strains than that of soluble S2P or S6P, or full-length S2P with its coding sequence matching mRNA-1273. The nAb responses elicited by S6P-HBsAgs persisted substantially longer than by soluble S2P or S6P and appeared to be enhanced by HBsAg pre-exposure. These data show that genetic delivery of SARS-CoV-2 S6P-HBsAg nanoparticles can elicit greater and more durable nAb responses than non-nanoparticle forms of stabilized spike. Our findings highlight the potential of S6P-HBsAgs as next generation genetic vaccine candidates against SARS-CoV-2.


Advances in giant unilamellar vesicle preparation techniques and applications.
Giant unilamellar vesicles (GUVs) are versatile and promising cell-sized bio-membrane mimetic platforms. Their applications range from understanding and quantifying membrane biophysical processes to acting as elementary blocks in the bottom-up assembly of synthetic cells. Definite properties and requisite goals in GUVs are dictated by the preparation techniques critical to the success of their applications. Here, we review key advances in giant unilamellar vesicle preparation techniques and discuss their formation mechanisms. Developments in lipid hydration and emulsion techniques for GUV preparation are described. Novel microfluidic-based techniques involving lipid or surfactant-stabilized emulsions are outlined. GUV immobilization strategies are summarized, including gravity-based settling, covalent linking, and immobilization by microfluidic, electric, and magnetic barriers. Moreover, some of the key applications of GUVs as biomimetic and synthetic cell platforms during the last decade have been identified. Membrane interface processes like phase separation, membrane protein reconstitution, and membrane bending have been deciphered using GUVs. In addition, vesicles are also employed as building blocks to construct synthetic cells with defined cell-like functions comprising compartments, metabolic reactors, and abilities to grow and divide. We critically discuss the pros and cons of preparation technologies and the properties they confer to the GUVs and identify potential techniques for dedicated applications.


High risk/high priority: familial hypercholesterolemia--a paradigm for molecular medicine.
Familial hypercholesterolemia provides an excellent model for demonstrating how disease prevention can be facilitated by molecular characterization of a genetic disease. To achieve the most efficient yield in terms of patient identification and coronary heart disease prevention, family information should be obtained in the primary care setting. In the majority of cases, measurement of cholesterol levels in a patient's relatives is sufficient to determine presence or absence of familial hypercholesterolemia, and DNA testing may be used in those cases in which cholesterol level is not diagnostic. DNA testing has enabled a more refined assessment of the absolute cardiovascular risks associated with familial hypercholesterolemia, which is currently estimated to have a 50% mortality rate by age 60. Recent investigations using DNA testing have suggested that familial hypercholesterolemia is implicated in one of 12 cases of cardiovascular disease in individuals aged <65 years. Only the most potent lipid-modifying therapies should be used in those found to be affected by this disorder. In this regard, it is noteworthy that the new statin rosuvastatin (Crestor; AstraZeneca) was recently shown to produce significantly greater low-density lipoprotein (LDL) cholesterol reductions and high-density lipoprotein (HDL) cholesterol increases than atorvastatin in a large study in patients with familial hypercholesterolemia, while bringing more of these patients to LDL cholesterol goals. Familial hypercholesterolemia should serve as a paradigm of molecular medicine: we understand the genetic defect, we have the tools to identify the individuals who are at high risk of disease because they have the defect, and we have therapies that can prevent clinical disease. It nevertheless requires effort on the part of clinicians to ensure that optimal risk assessment is performed and optimal treatment provided.


Detection and measurement of carbohydrate deficient transferrin in serum using immuno-capture mass spectrometry: diagnostic applications for annual ryegrass toxicity and corynetoxin exposure.
The neurological livestock disease annual ryegrass toxicity (ARGT) is caused by the ingestion of the naturally occurring glycolipid toxins - the corynetoxins. Corynetoxins also threaten human health as potential contaminants of the food supply. Presently, there are no routine diagnostic tests for corynetoxins-exposure in humans or livestock. Chronic ingestion of corynetoxins has been modeled in rats exposed to dietary tunicamycins for 12 months and carbohydrate deficient transferrin (CDT) has been previously identified as a candidate disease biomarker. Here, the technique of immuno-capture mass spectrometry (icMS) was used to evaluate serum levels of CDT, discriminating between control and tunicamycins-exposed rats with 85% accuracy. The icMS approach is based on the combination of specific transferrin enrichment with functionalized magnetic beads and automated matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). With no other clinically-relevant diagnostic tests available icMS could be readily adapted for high-throughput clinical assessment of corynetoxins-exposure in humans or livestock.


Percutaneous, implantless basal closing wedge osteotomy for hallux valgus: Surgical technique and preliminary results in 114 patients.
Percutaneous, implantless basal closing wedge osteotomy (PIBCO) is a new technique for hallux valgus (HV) deformity correction that does not need internal fixation. We present this technique and its short-term clinical outcomes for moderate-to-severe HV deformities. A retrospective review of 162 feet in 114 patients who underwent PIBCO of the first metatarsal (MT1) was conducted. Follow-up averaged 18.5 months. Outcomes were assessed using the visual analog scale (VAS), hallux valgus angle (HVA), intermetatarsal angle (IMA), and radiologic union. Complications were also assessed. Average VAS score improved from 6.2 to 1.0 (P < 0.001). HVA improved from 29.8° to 7.6° (P < 0.001). IMA improved from 14.5° to 6.3° (P < 0.001). A total of 8 major complications were noted (4.9%). Satisfactory HV deformity correction was achieved. However, some instances may require internal fixation in order to avoid complications related to instability and noncompliance of postoperative rehabilitation protocols.


The patient's perception of a delirium: A qualitative research in a Belgian intensive care unit.
This research aims to describe the intensive care patients' perception of a delirium. A hermeneutic qualitative research was designed using semi-structured interviews. Adult patients admitted between December 2011 and April 2012 to the intensive care unit of a Belgian public hospital, scoring positive for delirium at least once, were eligible for this study. At least 48hours after the last positive score for delirium, the patients could be interviewed. Data saturation was achieved after 30 patients. Several patients spontaneously indicated the recollection of the delirium, whereas others needed a few questions or needed the specificity of the syndrome to be pointed out. The analysis of the qualitative data resulted in four major themes: (1) contact and communication, (2) feelings, (3) sleep and time and (4) implication of the delirious episode. Interviewees recollected a vivid delirium with unrealistic scenes. The study delivered a first understanding of patients' perceptions during a delirium. This qualitative research tried to image the patients' perceptions providing nurses, physicians, other health-care workers as well as patients and their family with a better insight into the syndrome. Targeted interventions may be developed to relieve the burden of the syndrome.


The organization of corticothalamic projections: reciprocity versus parity.
All neocortical areas receive inputs from and project back to the thalamus. It is often said that the corticothalamic projections are organized in a way that reciprocates the spatial distribution of thalamocortical pathways. The present review examines to what extent this rule of reciprocity is actually supported by the most recent neuroanatomical data, particularly those relating to the central organization of the vibrissal sensory system in the rat. A critical survey of previous studies is made and new results are presented concerning the fine-grained organization of corticothalamic projections in this sensory system. Together, prior results and the present set of new data confirm the existence of both, reciprocal and nonreciprocal patterns of corticothalamic connectivity. This conclusion leads us to propose that the spatial organization of corticothalamic connections complies with a more fundamental rule, the rule of parity, from which reciprocity follows as a general, but not obligatory consequence. The rule of parity states that the distribution of corticothalamic projections across and within the thalamic nuclei is determined by the branching patterns of the different classes of prethalamic afferents. The anatomical, developmental and physiological consequences of this rule are discussed. The rule of parity suggests that, according to the behavioral context, both prethalamic and corticothalamic pathways may function in a feedback mode.


The utility of PAX8 and IMP3 immunohistochemical stains in the differential diagnosis of benign, premalignant, and malignant endocervical glandular lesions.
Glandular lesions of the endocervix can be diagnostically challenging and occasionally the differential diagnosis includes endocervical adenocarcinoma in situ (EC AIS) and well-differentiated endocervical adenocarcinoma (ECA). PAX8 and IMP3 are two markers which have not been well studied in the endocervix. Our aim was to evaluate their immunohistochemical (IHC) expression in benign and malignant endocervical glandular lesions as well as to compare them to the traditionally used panel (Ki-67, p16, CEA). We searched our surgical pathology files for a cohort of benign endocervical glandular lesions as well as premalignant and malignant groups including EC AIS and ECA. An IHC panel consisting of PAX8, IMP3, Ki-67, p16, and CEA was performed on all cases. Immunoreactivity was scored on a degree of positivity (S0=no immunoreactivity, S1=up to 10% cells, S2=between 10 and 50% cells, S3=>50% cells) and intensity (Int0 - absent, Int1 - mild/faint, Int2 - moderate, Int3 - strong). PAX8 showed diffuse positivity (S3) with at least a moderate intensity of staining (Int2) in the benign group. PAX8 was focal (S1) in ECA and faint (Int1), compared to EC AIS, which was moderate (S2) and faint (Int1). IMP3 expression was focal in the benign group (S1), moderate (S2) in EC AIS and moderate-to-diffuse (S2-3) in ECA. IMP3 intensity was faint (Int1) in benign lesions, moderate (Int2) in EC AIS, and strong (Int3) in ECA. Significant Ki-67, p16, and CEA expression was noted in the premalignant/malignant cohort. PAX8 and IMP3 can be helpful in the differential diagnosis of benign vs. malignant endocervical glandular lesions. Our study, however, shows that there is some degree of overlap of staining in both the benign and malignant group. As such, PAX8 and IMP3 should always be interpreted with caution and in combination with the histomorphology.


[Safety of use of velaglucerase in 2 patients with type 1 Gaucher's disease].
The incidence of immunologic reactions in patients with Gaucher's disease (GD) on enzymatic replacement therapy with imiglucerase is about 17% and related with the presence of non-neutralizing immunoglobulin G antibodies. The clinical trials with a new enzyme obtained in human cells (GA-GCB-velaglucerase) have demonstrated absence of immune reactions and no antibodies against the enzyme in spite of some patients had previous developed antibodies against imiglucerase. We present 2 clinical cases of patients diagnosed with EG in childhood and who developed antibodies and important imiglucerase immunoallergic adverse reaction during the imiglucerase perfusion, indicating systematic administration of steroids and antihistamines prior to each perfusion and perfusion time > 4h.


Correlations between mean echogenicity and material properties of normal and diseased equine superficial digital flexor tendons: an in vitro segmental approach.
The objective of this study was to test the hypothesis that tendon echogenicity is associated with the material properties of the corresponding tendon site, especially in case of lesions, due to local changes in tendon matrix composition. Four normal and nine spontaneously injured equine superficial digital flexor tendons (SDFT) were isolated then ultrasonographically examined under tension, in a special device placed in a water bath. Ultrasonographic transversal images (7.5MHz linear transducer) of five segments along each tendon were digitized, and analyzed in order to measure the mean cross-sectional area (MCSA) and mean echogenicity (ME) of each segment. The tendons were then tested in traction until rupture in a testing machine. For each segment, stress and strain were determined throughout the test, and the elastic modulus (EM) was evaluated. The tendon lesions were also documented by histology. No correlation was found between ME and the material properties of normal tendon segments. At the rupture sites of the nine diseased tendons, ME was positively correlated with maximal stress and EM, whereas no correlation was demonstrated with maximal strain. Besides, a positive correlation was demonstrated between ME and both MCSA and EM, when the three metacarpal segments of the diseased tendons were considered. Although ME gives only rough information about tendon matrix structure, it does show, under these in vitro conditions, significant correlations with material properties of pathological tendon segments, which may improve the functional significance and therefore the prognostic value of the ultrasonographic examination of tendon lesions.


Involvement of the Rho-kinase/myosin light chain kinase pathway on human monocyte chemotaxis induced by ATL-1, an aspirin-triggered lipoxin A4 synthetic analog.
Lipoxins (LX) are arachidonic acid metabolites able to induce monocyte chemotaxis in vitro and in vivo. Nonetheless, the signaling pathways mediating this process are yet unclear. In this study, we have investigated the mechanisms associated with human monocyte activation in response to 15-epi-16-(para-fluoro)-phenoxy-LXA4 (ATL-1), a stable 15-epi-LXA4 analog. Our results demonstrate that ATL-1-induced monocyte chemotaxis (10-300 nM) is inhibited by pertussis toxin, suggesting an effect via the G-protein-linked LXA4 receptor. Monocytes stimulated with the analog presented an increased ERK-2 phosphorylation, which was reduced by PD98059, a selective inhibitor of the MEK 1/2 pathway. After exposure of the cells to ATL-1, myosin L chain kinase (MLCK) phosphorylation was evident and this effect was inhibited by PD98059 or Y-27632, a specific inhibitor of Rho kinase. In addition, Y-27632 abolished ERK-2 activation, suggesting that the MAPK pathway is downstream of Rho/Rho kinase in MLCK activation induced by ATL-1. The specific MLCK inhibitor ML-7, as well as Y-27632, abrogated monocyte chemotaxis stimulated by the analog, confirming the central role of the Rho kinase/MLCK pathway on ATL-1 action. Together, these results indicate that ATL-1 acts as a potent monocyte chemoattractant via Rho kinase and MLCK. The present study clarifies some of the mechanisms involved on the activation of monocytes by LXs and opens new avenues for investigation of these checkpoint controllers of inflammation.


Usefulness of N-terminal pro-B-type natriuretic peptide (NT-ProBNP) as a marker for cardiotoxicity and comparison with echocardiography in paediatric carbon monoxide poisoning.
To demonstrate the usefulness of N-Terminal Pro-B-Type natriuretic peptide (NT-proBNP) as an early biomarker of carbon monoxide-induced myocardial injury in children. It also aimed to identify the correlation between NT-proBNP and left ventricular systolic dysfunction findings shown by echocardiography. Prospective, observational study conducted at a paediatric emergency department between October 2017 and April 2019 which involved children aged 0-17 years. The patients were divided into three groups based on severity; mild, moderate and severe groups. The patient characteristics, carboxyhaemoglobin, CK-MB Mass (CKMB-M), troponin-T, and NT-proBNP levels were measured, and echocardiography was performed and left ventricular ejection fraction was measured. Sixty-nine patients and 60 healthy controls were included. Male gender, younger age, higher carboxyhaemoglobin levels, and altered mental status were found as independent predictors of carbon monoxide-induced myocardial injury. If the cut-off value for NT-proBNP level is >480 pg/ml, the sensitivity-specificity for decreased left ventricular ejection fraction, which is the strongest carbon monoxide-induced myocardial injury sign, were 100-96%, respectively. A high negative correlation was found between NT-proBNP levels and left ventricular ejection fraction (r = -0.769, p < 0.01) in the carbon monoxide poisoning group, and there was a positive correlation between the carboxyhaemoglobin and NT-proBNP levels (r = 0.583, p < 0.01). Echocardiography is an ideal tool and very sensitive, but its routine use is limited due to its non-availability. An increased level of NT-proBNP (>480pg/ml) may be useful as an ideal biomarker for early detection of carbon monoxide-induced myocardial injury sign and reduced left ventricular ejection fraction which is the most crucial point in making a decision on hyperbaric oxygen therapy.


Correction: Arterial tortuosity syndrome: 40 new families and literature review.
In the published version of this paper the author Neus Baena's name was incorrectly given as Neus Baena Diez. This has now been corrected in both the HTML and PDF versions of the paper.


Influence of factor D concentrations on fluid phase C3 activation, lysis of rabbit erythrocytes and solubilization of immune complexes.
Factor D depleted serum did not support hemolysis of rabbit erythrocytes and solubilization of performed immune complexes. Fluid phase C3 cleavage increased in a dose dependent manner when D protein was added to normal or to factor D depleted serum. During short incubation factor D concentrations were correlated with the capacity of serum to solubilize immune complexes and to lyse rabbit erythrocytes. With prolonged incubation, the hemolytic activity decreased in a factor D dose dependent manner. This was probably due to fluid phase breakdown of C3 and factor B in the presence of high factor D concentrations. Hypocomplementemic sera from patients with active systemic lupus erythematosus (SLE) did not support solubilization of bovine serum albumin (BSA) anti-BSA complexes when factor D was added in excess. Patients with polycystic kidney disease with reduced renal function and high factor D concentrations showed increased concentrations of circulating C3d/dg fragments. The possibility was considered that high factor D concentrations in uremia might promote fluid phase C3 degradation and thereby limit the in vivo efficiency of alternative pathway activation on target surfaces.


Microbiomes of China's Space Station During Assembly, Integration, and Test Operations.
Sufficient evidence indicates that orbiting space stations contain diverse microbial populations, which may threaten astronaut health and equipment reliability. Understanding the composition of microbial communities in space stations will facilitate further development of targeted biological safety prevention and maintenance practices. Therefore, this study systematically investigated the microbial community of China's Space Station (CSS). Air and surface samples from 46 sites on the CSS and Assembly Integration and Test (AIT) center were collected, from which 40 bacteria strains were isolated and identified. Most isolates were cold- and desiccation-resistant and adapted to oligotrophic conditions. Bacillus was the dominant bacterial genus detected by both cultivation-based and Illumina MiSeq amplicon sequencing methods. Microbial contamination on the CSS was correlated with encapsulation staff activities. Analysis by spread plate and qPCR revealed that the CSS surface contained 2.24 × 103-5.47 × 103 CFU/100 cm2 culturable bacteria and 9.32 × 105-5.64 × 106 16S rRNA gene copies/100cm2; BacLight™ analysis revealed that the viable/total bacterial cell ratio was 1.98-13.28%. This is the first study to provide important systematic insights into the microbiome of the CSS during assembly that describes the pre-launch microbial diversity of the space station. Our findings revealed the following. (1) Bacillus strains and staff activities should be considered major concerns for future biological safety. (2) Autotrophic and multi-resistant microbial communities were widespread in the AIT environment. Although harsh cleaning methods reduced the number of microorganisms, stress-resistant strains were not completely removed. (3) Sampling, storage and analytical methods for the space station were thoroughly optimized, and are expected to be applicable to low-biomass environments in general. Microbiology-related future works will follow up to comprehensively understand the changing characteristics of microbial communities in CSS.


Genotyping of Giardia intestinalis from domestic and wild animals in Japan using glutamete dehydrogenase gene sequencing.
To determine the genotypes of Giardia intestinalis from domestic and wild animals in Japan, Giardia isolates obtained from feces of 24 dogs kept in households and breeding kennels, three companion cats, five dairy calves and three wild monkeys, Macaca fuscata, were genotyped using the 177 bp sequence of the glutamete dehydrogenase gene (gdh). The genotypes were assemblages A, C, D or A/D for dog isolates, Assemblage F for cat isolates, assemblages A or E for calf isolates and assemblage B for monkey isolates. This is the first report on the genotypes of Giardia isolates from cats, calves and wild monkeys in Japan.


Thoracic aortic aneurysms and pregnancy.
Half of acute aortic dissection in women under the age of 40 occurs during pregnancy or peripartum period. Marfan syndrome is the most common syndromic presentation of ascending aortic aneurysm, but other syndromes such as vascular Ehlers-Danlos syndrome, Loeys-Dietz syndrome and Turner syndrome also have ascending aortic aneurysms and the associated cardiovascular risk of aortic dissection and rupture. Management of aortic root aneurysm has been established in recent recommendations, even if levels of evidence are weak. Pregnancy and postpartum period should be followed very closely and determined to be at high risk. Guidelines suggest that women with aortopathy should be counseled against the risk of pregnancy and about the heritable nature of the disease prior to pregnancy.


Conjugated Acetylenic Polymers Grafted Cuprous Oxide as an Efficient Z-Scheme Heterojunction for Photoelectrochemical Water Reduction.
As attractive materials for photoeletrochemical hydrogen evolution reaction (PEC HER), conjugated polymers (e.g., conjugated acetylenic polymers [CAPs]) still show poor PEC HER performance due to the associated serious recombination of photogenerated electrons and holes. Herein, taking advantage of the in situ conversion of nanocopper into Cu2 O on copper cellulose paper during catalyzing of the Glaser coupling reaction, a general strategy for the construction of a CAPs/Cu2 O Z-scheme heterojunction for PEC water reduction is demonstrated. The as-fabricated poly(2,5-diethynylthieno[3,2-b]thiophene) (pDET)/Cu2 O Z-scheme heterojunction exhibits a carrier separation efficiency of 16.1% at 0.3 V versus reversible hydrogen electrode (RHE), which is 6.7 and 1.4-times higher respectively than those for pDET and Cu2 O under AM 1.5G irradiation (100 mW cm-2 ) in the 0.1 m Na2 SO4 aqueous solution. Consequently, the photocurrent of the pDET/Cu2 O Z-scheme heterojunction reaches ≈520 µA cm-2 at 0.3 V versus RHE, which is much higher than pDET (≈80 µA cm-2 ), Cu2 O (≈100 µA cm-2 ), and the state-of-the-art cocatalyst-free organic or organic-semiconductor-based heterojunctions/homojunctions photocathodes (1-370 µA cm-2 ). This work advances the design of polymer-based Z-scheme heterojunctions and high-performance organic photoelectrodes.


Long-term outcome in acquired aplastic anemia treated with an intensified dose schedule of horse antilymphocyte globulin in combination with androgens.
Aplastic anemia (AA) is a rare hematopoietic stem cell disease, which can be treated with horse antilymphocyte globulin (ALG) for patients not eligible for bone marrow transplantation. ALG gives about 60% overall survival rate (OS) after 5 years, a 30% of persistent complete remission and a 20% early death rate related to failure. ALG has been incriminated in the emergence of 10 to 20% therapy-related AML/MDS (t-AML/MDS) with the usual doses. Questions remain whether higher doses of ALG could improve the response and OS rates and whether the combination with androgens is able to protect patients from t-AML/MDS. We have carried out a single institutional retrospective study of 87 AA treated with higher doses of ALG, twice the usual posology (140 mg/kg instead of 75 mg/kg), combined to androgens. The overall response rate was 77% and the OS rate at 5 years was 78%. Androgens in combination with ALG improved response and OS rates. At diagnosis, 6% of AA had an abnormal karyotype using conventional cytogenetic not related to any time-to-event. Two patients displayed a cytogenetic conversion related to the occurrence of secondary malignancies. The incidence of t-AML/MDS was 2.3% with an estimated 10-year cumulative incidence of 3.1. Our results show that higher doses of ALG combined to androgens are feasible and give results close to those recently describe with the immunosuppressive treatments including ALG associated to cyclosporine, with a low SMD/AML incidence rate.


Understanding the longitudinal relationship between substance use and violent victimization among street-based women who exchange sex in Baltimore, Maryland.
Women who exchange sex (WES) experience extensive interpersonal violence from multiple perpetrators. Violence towards WES contributes to poor mental and behavioral health outcomes, including high rates of drug use. However, it is difficult to disentangle the temporal relationship between drug use and violence among WES. We used data from 251 WES, who completed baseline and 6-month follow up surveys. WES reported baseline sociodemographic characteristics, including homelessness and hunger. Participants reported their drug use by type and violent experiences by perpetrator at each time point. We conducted a path analysis examining the associations between drug use and violent victimization over time. Participants were on average 37.8 years old, non-Hispanic White (57.4%) and experiencing high levels of structural vulnerability (59.4% homelessness; 58.6% weekly hunger). Drug use and violence were significantly correlated within each time point. Prospectively, baseline violent victimization was significantly associated with drug use (ß (SE) = 0.13 (0.06)) and violence (ß (SE) = 0.47 (0.05)) at follow up. Baseline drug use was associated with drug use at follow up (ß (SE) = 0.45 (0.05)) but was not significantly associated with violence at follow up (ß (SE) = 0.10 (0.06)). Violence and drug use are closely linked in this population; and violence appears to facilitate sustained drug use. Interventions to address the dual epidemics of violence and substance use in this population should address underlying trauma as well as socio-structural drivers of violence as well as tailored harm reduction services for this population.


Multiple nevoid basal-cell carcinoma syndrome (Gorlin's syndrome): possible confusion with metastatic medulloblastoma. Case report.
The authors report a diagnostic dilemma involving a child who, 8 years previously, had total excision of a medulloblastoma. On x-ray studies, lytic lesions of the skull were seen. The differential diagnosis and some of the clinical and pathological aspects of the nevoid basal-cell carcinoma syndrome versus metastases are discussed.


The use of artificial intelligence models to predict survival in patients with laryngeal squamous cell carcinoma.
Most recent survival prediction has been based on TNM staging, which does not provide individualized information. However, clinical factors including performance status, age, sex, and smoking might influence survival. Therefore, we used artificial intelligence (AI) to analyze various clinical factors to precisely predict the survival of patients with larynx squamous cell carcinoma (LSCC). We included patients with LSCC (N = 1026) who received definitive treatment from 2002 to 2020. Age, sex, smoking, alcohol consumption, Eastern Cooperative Oncology Group (ECOG) performance status, location of tumor, TNM stage, and treatment methods were analyzed using deep neural network (DNN) with multi-classification and regression, random survival forest (RSF), and Cox proportional hazards (COX-PH) model for prediction of overall survival. Each model was confirmed with five-fold cross validation, and performance was evaluated using linear slope, y-intercept, and C-index. The DNN with multi-classification model demonstrated the highest prediction power (1.000 ± 0.047, 0.126 ± 0.762, and 0.859 ± 0.018 for slope, y-intercept, and C-index, respectively), and the prediction survival curve showed the strongest agreement with the validation survival curve, followed by DNN with regression (0.731 ± 0.048, 9.659 ± 0.964, and 0.893 ± 0.017, respectively). The DNN model produced with only T/N staging showed the poorest survival prediction. When predicting the survival of LSCC patients, various clinical factors should be considered. In the present study, DNN with multi-class was shown to be an appropriate method for survival prediction. AI analysis may predict survival more accurately and improve oncologic outcomes.


Influence of plant polyphenols and medicinal plant extracts on antibiotic susceptibility of Escherichia coli.
To investigate the influence of polyphenols and plant extracts on the susceptibility of Escherichia coli to antibiotics. Susceptibility of E. coli to antibiotics in the presence of extracts and polyphenols was estimated by the determination of the minimum inhibitory concentrations (MICs). To study gene expression, we used strains of E. coli carrying fusions between promoters of genes katG, sodA, iucC and structural β-galactosidase gene. Treatment with polyphenols and some plant extracts significantly decreased the antibacterial effects of antibiotics, to a larger extent, ciprofloxacin. The most remarkable protective effect was observed for the extracts of Chamerion (Epilobium) angustifolium, Filipendula vulgaris, Tanacetum vulgare and Serratula coronata. These extracts increased the MICs of ciprofloxacin by four and more times. In case of kanamycin, extracts of Artemisia austriaca and Artemisia pontica increased MICs by four and eight times, respectively. Polyphenol quercetin also caused protective effect against ciprofloxacin, increasing the MIC by four times. A positive correlation was found between protective effects of polyphenols and extracts and their antioxidant activity. Medicinal plant extracts and polyphenols may protect cells of E. coli against antibiotic toxicity. The results of this study may be used to enhance the efficiency of antibacterial therapies.


Apocrine Hidrocystoma: A Rare Case Report.
Hidrocystoma is a cystic tumor originating from a dilated sweat gland. The tumor is typically small and located predominantly on the face, particularly in the eyelid margins. They are two classical types of hidrocystomas i.e., Apocrine and Eccrine. Apocrine hidrocystomas are cystic lesions that arise from the apocrine secretory coil and Eccrine hidrocystomas represent retention cysts of the eccrine duct. Multiple apocrine hidrocystomas confined to the eyelids have been recognized as a feature of a new variant of ectodermal dysplasia. Here we present a rare case of Apocrine hidrocystoma of supraorbital area for which excisional biopsy of the lesion was performed. Histopathological evaluation proved the lesion was a unilocular cyst lined by a double-layered epithelium of the apocrine type. The purpose of this paper is to report the unique occurrence of a Supra orbital apocrine hidrocystoma which was clinically as a sebaceous cyst and to discuss its differential diagnosis with other more common supraorbital and face lesions.


Partition of Omega-like facility into two configurations of 24 and 36 laser beams to improve implosion performance.
An Omega-like beam configuration is considered where the 60-beam layout can be separated into two independent sub-configurations with 24 and 36 laser beams, each minimizing direct drive illumination non-uniformity. Two different laser focal spot profiles, one associated with each configuration, are proposed to apply the zooming technique in order to increase the laser-target coupling efficiency. This approach is used by 1D hydrodynamics simulations of the implosion of a direct-drive capsule characterized by a relatively large aspect ratio A = 7 and an optimized laser pulse shape delivering a maximum of 30 TW and 30 kJ, with different temporal pulse shapes in each of the two sets of beams. It is shown that zooming allows for an optimistic 1D thermonuclear energy gain greater than one while without zooming the thermonuclear gain remains largely below one. While this is incompatible with the as-built Omega laser, it provides a promising option for a future intermediate-energy direct drive laser system.


Improved glycaemic control and lower hypoglycaemia risk with reduced prior oral antidiabetes drug therapy in patients with type 2 diabetes treated with insulin glargine 300 U/mL.
Data from the EDITION 3 randomized study and the Clinformatics claims database were analysed to determine whether insulin glargine 300 U/mL (Gla-300) could provide insulin-naive patients with type 2 diabetes (T2D) on oral antidiabetes drugs (OADs) with reductions in prior OAD therapy without compromising glycaemic control, and while preserving its known low incidence of hypoglycaemia compared with insulin glargine 100 U/mL (Gla-100). Patient-level data from EDITION 3 and de-identified data from the Clinformatics real-world claims database were analysed. At baseline, 70% of patients in EDITION 3 were on a background of ≥2 OADs. Among the 435 and 437 patients who initiated basal insulin with Gla-300 and Gla-100, respectively, at Month 6, 336 (77%) and 338 (77%) were using ≤1 OAD. Adding Gla-300 or Gla-100 similarly allowed for a reduction in background OAD medication in the Clinformatics dataset (N = 6430), such that, at 6 months postbasal insulin initiation, 14% of patients were no longer taking any OADs. In the analysis of the EDITION 3 study, reduction in OAD burden did not compromise glycaemic benefit, and the low incidence of hypoglycaemia associated with Gla-300 compared with Gla-100 was also preserved. Documented symptomatic hypoglycaemia (blood glucose ≤70 mg/dL) occurred in 30.5% vs 41.0% of patients treated with Gla-300 and Gla-100, respectively (P = 0.0442). Patients with T2D who initiate basal insulin with Gla-300 could potentially reduce their prior OAD use without compromising glycaemic control and with less hypoglycaemia than with Gla-100.


Greasing the path to BAX/BAK activation.
BAX/BAK activation leading to mitochondrial outer-membrane permeabilization is a key commitment point in apoptosis. Chipuk et al. now identify two sphingolipids as specific cofactors for BAX/BAK activation that lower the threshold for apoptosis-associated cytochrome c release. Association of mitochondria with other cellular membrane compartments is required for BAK/BAX exposure to these sphingolipids.


Small cell carcinoma of the tonsil.
Extrapulmonary small cell carcinomas are rare tumors of the APUD system. They are most commonly seen in the esophagus with rare cases reported in the head and neck. We present the sixth reported case of primary small cell carcinoma of the tonsil. These tumors are usually widely disseminated initially. Aggressive locoregional treatment with radiation is the treatment of choice. Systemic treatment is needed for presumed metastatic disease. Surgery may be an adjunct treatment used for locoregional control.


Catecholaminergic mechanisms of feeding-related lateral hypothalamic activity in the monkey.
The functional role of the catecholaminergic mechanism in the lateral hypothalamus (LHA), in feeding behavior of the monkey was investigated by single neuron activity recording and electrophoretic application of dopamine (DA), noradrenaline (NA) and their antagonists. The feeding paradigm had 4 phases: cue light (CL) signaled start of bar press; bar press (BP, 20-30 times); short cue tone (CT) triggered by last bar press signaled presentation of food; and ingestion-reward (RW). Of 312 neurons tested, 189 (61%) responded in one or more phases of the feeding task. Two types of response were observed: CL- or CT-related transient, and BP- or RW-related long-lasting responses. These feeding-related responses depended on the nature of the food and on the hunger-satiety level. DA excited or inhibited different neurons, while NA mainly inhibited firing. DA-sensitive neurons responded more often in the feeding task than insensitive neurons due mainly to differences in responsiveness to CL on (chi 2 test, P less than 0.01), at motor initiation, and during BP (P less than 0.05). Spiperone blocked the former two responses. NA-sensitive neurons responded more often in the feeding task due to responsiveness during BP and RW (P less than 0.01). Sotalol blocked some BP-related responses, and phenoxybenzamine and sotalol blocked the CT-related responses. The data suggest that dopaminergic and noradrenergic inputs in the LHA are crucial in task initiation and reward processing, respectively. Integration of these catecholaminergic and other inputs in the LHA might be important in accomplishing motivated feeding.


CSF myelin basic protein levels in acute optic neuritis and multiple sclerosis.
Normal CSF-MBP levels as determined by a RIA were less than 6.2 ng/ml CSF (mean 3.9). Eighty percent of patients with acute optic neuritis have CSF-MBP levels greater than 6.2 ng/ml (mean 7.6 ng/ml CSF). Five of 7 patients with acute internuclear ophthalmoplegia due to an initial exacerbation of demyelination have CSF-MBP levels above 6.2 ng/ml (mean 6.8 ng/ml). Fifty percent of MS patients with chronic progressive disease have CSF-MBP levels above 6.2 ng/ml (mean 6.7 ng/ml). MS patients experiencing monosymptomatic exacerbations show elevated CSF-MBP levels in 75% in 75% of cases (mean 8.2 ng/ml). MS patients experiencing polysymptomatic exacerbations show significantly higher levels of CSF-MBP (mean 22.3 ng/ml) than the patients with monosymptomatic exacerbations. Ninety-five percent of MS patients experiencing polysymptomatic exacerbations have elevated levels of CSF-MBP.


Adenovirus-mediated gene transfer in vivo: an approach to reduce oxidative stress.
Replication-deficient adenoviruses are used as vectors to study function of genes and to treat hypertension and cardiovascular diseases in preclinical studies. The purpose of this chapter is to provide an example of applications of the "first-generation," E1-deleted and partially E3-deleted, human adenovirus type 5 vector, to test the hypothesis that gene transfer of a primary antioxidant enzyme, human extracellular superoxide dismutase (ECSOD), reduces arterial pressure in a genetic animal model of hypertension. Two concepts in application of gene transfer in vascular biology are illustrated. First, the liver, by iv injection of an adenoviral vector, can function as the source for abundant amounts of a transgene product, with profound vascular effects, when the transgene encodes a secreted protein. Second, the specific function of a domain of the transgene product can be studied by preparation and injection of isogenic vectors that express the identical product with or without a domain.


Dual Effects of Limbic Seizures on Psychosis-Relevant Behaviors Shown by Nucleus Accumbens Kindling in Rats.
A paradox in epilepsy and psychiatry is that temporal lobe epilepsy is often predisposed to schizophrenic-like psychosis, whereas convulsive therapy can relieve schizophrenic symptoms. We have previously demonstrated that the nucleus accumbens is a key structure in mediating postictal psychosis induced by a hippocampal electrographic seizure. The purpose of this study is to test a hypothesis that accumbens kindling cumulating in a single (1-time) or repeated (5-times) convulsive seizures have different effects on animal models of psychosis. Electrical stimulation at 60 Hz was applied to nucleus accumbens to evoke afterdischarges until one, or five, convulsive seizures that involved the hind limbs (stage 5 seizures) were attained. Behavioral tests, performed at 3 days after the last seizure, included gating of hippocampal auditory evoked potentials (AEP) and prepulse inhibition to an acoustic startle response (PPI), tested without drug injection or after ketamine (3 mg/kg s.c.) injection, as well as locomotion induced by ketamine or methamphetamine (1 mg/kg i.p.). Compared to non-kindled control rats, 1-time, but not 5-times, convulsive seizures induced PPI deficit and decreased gating of hippocampal AEP, without drug injection. Compared to non-kindled rats, 5-times, but not 1-time, convulsive seizures antagonized ketamine-induced hyperlocomotion, ketamine-induced PPI deficit and AEP gating decrease. However, both 1- and 5-times convulsive seizures significantly enhanced methamphetamine-induced locomotion as compared to non-kindled rats. Accumbens kindling ending with 1 convulsive seizure may induce schizophrenic-like behaviors, while repeated (≥5) convulsive seizures induced by accumbens kindling may have therapeutic effects on dopamine independent psychosis.


[The teaching of surgical specialties in France to foreign students: apropos of an inter-university specialty diploma in orthopedic surgery and traumatology].
Foreign doctors who wish to be specialised in a particular branch mainly register themselves for a D.I.S. (Specialised Inter-university Diploma). The curriculum to this diploma is described through its Orthopaedics and Traumatologic Surgery branch and its drawbacks are analysed, namely lack of strict selection at entrance, insufficient theoretical courses and specially lack of practical training. More over, figures concerning the first batch show a large number of students registered in the first year while only a few succeeded the final examination. The consequences of such a poor formation might be serious. Solutions are proposed after comparison with the organisations retained in other countries. Any reform should firstly describe the aims of this postgraduate educational programme to foreign students.