[Result of 3 years of screening for preclinical phase of juvenile insulin-dependent diabetes mellitus].
We screened 1,000 individuals for pre-type I diabetes mellitus: 927 were first degree relatives of patients treated at our institution, 31 other had related autoimmune diseases, 42 had fortuitously discovered slight hyperglycemia. Islet cell antibodies were present in 31 subjects, 13 adults and 18 children. Among these 18 children, 7 also had complement-fixing islet cell antibodies, and 5 anti-insulin antibodies. All but one initially had a normal insulin response to intravenous glucose. The child with the abolished response, as well as another whose insulin secretion fell down during the study period, became diabetic. Based on these preliminary data, we are developing large scale family screening of pre-type I diabetes.


Design and performance analysis of a parabolic trough power plant under the climatological conditions of Tamanrasset, Algeria.
Algeria's energy demands are tremendously growing, and on the African continent it ranks among the countries with the highest energy consumption. To counter its growing energy demand, the country is progressively adopting renewable energy technologies, although conventional energy technologies still play a central role in its electricity production. The huge solar energy potential in Algeria can be exploited and utilized to meet the country's growing energy demand with minimal greenhouse gas production. Given that concentrating solar power is viewed as one of the most promising alternatives in the field of solar energy utilization, this study investigates the viability of a 100 MW parabolic trough-based power plant at Tamanrasset, Algeria. The plant was simulated in the System Advisor Model software considering the actual electricity load profile of the targeted location and implementing two different condenser types: evaporative and air-cooled. By comparing the plant's electricity production to the city's real load, the plant was in position of supplying about 78% and 60% of the city's electricity demand during the winter and summer seasons, respectively. The results show that implementation of such CSP plants could play an important role in meeting the energy demand as well as mitigating climate change through greenhouse emissions avoided in electricity generation process.


[Endoscopic ultrasound in the long-term follow-up of primary lymphomas of the stomach under conservative therapy].
The stomach is the main site of primary extranodular manifestation of non-Hodgkin's lymphomas. Besides clinical staging additional to histological diagnoses, the endoscopic ultrasound (EUS) also becomes more important during follow-up courses of conservative therapy regimens (e. g. H.p. eradication; radiochemotherapy). The aim of the present study was to assess the impact of EUS during long-term observation of primary gastric lymphomas and to outline possible changes of the gastric wall. Within the scope of 2 prospective multicenter study on primary gastrointestinal non-Hodgkin's lymphomas (GIT-NHL), which were performed at Muenster University Hospital, 26 patients undergoing conservative treatment were examined with endoscopic ultrasound at a three-month interval between 01/1992 and 11/1998. The mean survey period was 28 months (range 7-62). In 22 patients over a period of 21 months (range 4-51) a histological proven complete remission (CR) was found. In 2 patients only a partial remission (PR) was achieved within a time period of seven respectively eight months of survey. Two other patients developed early relapse of non-Hodgkin's lymphoma. In patients with CR the endoscopic ultrasound showed a highly significant decrease of gastric wall thickness 7 and 12 months after therapy was started. On average after 4.6 months enlarged lymph nodes were no more detectable, after 5.5 months thickness of the gastric wall and finally after 6.6 month the previous abolished layering of the gastric wall returned to normal. In patients with gastric non-Hodgkin's lymphomas endoscopic ultrasound seems to be the only valid method which demonstrates early changes of the gastric wall and its layering in an appropriate way and might therefore in addition be capable to differentiate between CR, recurrent or refractory non-Hodgkin's lymphoma.


[Physicotechnical and dosimetric support of human whole-body irradiation in a standard medical source of photon radiation].
The paper is concerned with physicotechnical and dosimetric support of technology of therapeutic whole-body irradiation on a serial gamma apparatus ROKUS, with which a majority of radiological institutions in the USSR are fit out. Technology consists of the following procedures: patient positioning with relation to a source with a horizontal axis of radiation. Correction of dose distribution by means of a three-element compensator taking into account patient's constitutional peculiarities and preradiation preparation data; double irradiation in the bilateral regimen in the supine position.


Characterization of phosphofructokinase II and regulation of fructose 2,6-bisphosphate levels in Trichoderma reesei.
Phosphofructokinase II (PEK II) from Trichoderma reesei was partially purified (247-fold). The calculated Km values for fructose 6-phosphate and ATP were 0.7 mM and 40 microM, respectively. Upon incubation in the presence of [gamma-32P]ATP, the enzyme formed a radioactive phosphoprotein with molecular mass of 67 kDa in autoradiography analysis after SDS-PAGE. Upon incubation in the presence of ATP-Mg and the catalytic subunit of cAMP-dependent protein kinase, its activity was not modified. The same result was obtained when a cell-free extract of T. reesei was incubated with ATP-Mg and cAMP. 2,4-Dinitrophenol caused a transient rise in cAMP levels in the fungal cell. The results provide evidence that the fructose 2,6-bisphosphate level in T. reesei is independent of cAMP concentrations and not related to a cAMP-dependent mechanism, but to the availability of substrate fructose 6-phosphate.


Effect of intraoperative infusion of sufentanil versus remifentanil on postoperative shivering in Korea: a prospective, double-blinded, randomized control study
The number of published papers that compare the incidence of sufentanil- and remifentanil-related postoperative shivering is insufficient. We investigated the incidence of postoperative shivering after total intravenous anesthesia with either sufentanil or remifentanil in patients who underwent elective surgery. Eighty-three patients, with a physical status classified as American Society of Anesthesiologists I or II, were randomly allocated to either the remifentanil–propofol (RP group, n = 40) or sufentanil–propofol (SP group, n = 43) group. The primary endpoint was the incidence of postoperative shivering 1 h after entering the recovery room. The secondary endpoints were intraoperative core temperatures of the esophagus and tympanic membrane at 30 min after the induction of anesthesia and at the end of surgery. The overall postoperative shivering incidence was not significantly different between the RP (15%) and SP (11.6%) groups (P = 0.651). The intraoperative temperatures and their changes (the temperature 30 min after induction minus that after surgery) as measured at the distal esophagus and tympanic membrane were not significantly different between the RP and SP groups. The incidence of postoperative shivering related to sufentanil was less than that related to remifentanil, with no significant differences in the intraoperative core temperatures.


Arterial vasoconstrictor therapy for bleeding oesophageal varices.
Upper gastrointestinal bleeding in patients with hepatic cirrhosis carries considerable mortality. Difficulties are encountered both in determining the source of bleeding and in controlling blood loss. The techniques of selective visceral angiography not only supply diagnostic information, but can be used to administer selective intra-arterial vasoconstrictor therapy to control blood loss. We report our experience with 28 patients in whom angiography was performed with particular reference to six patients treated with selective vasoconstrictor therapy. Although the precise role of the technique is not yet established, early experience is most promising. We believe it will play an important role in a difficult group of patients in the future and may well supplant present methods of controlling bleeding.


Magnetic resonance imaging of the heart.
Magnetic resonance imaging (MRI) is a completely noninvasive technique for the evaluation of the cardiovascular system. With a multi-section technique and the spin echo pulse sequence the entire heart can be examined within six to ten minutes. All our cardiac MR studies were performed with electrocardiographic (ECG) gating, to obtain adequate resolution of the cardiac structures. With this technique, patients and animals with a variety of cardiac abnormalities were studied. The examined pathologic conditions included acute and chronic myocardial infarctions and their complications, hypertrophic and congestive cardiomyopathies, congenital heart diseases and pericardial diseases. MRI offers an enormous potential for cardiovascular diagnosis, even beyond the demonstration of pathoanatomy, because of the capability for direct tissue characterization and blood flow measurements.


Comparative Evaluation of Clinical Efficacy and Safety of Collagen Laminin-Based Dermal Matrix Combined With Resveratrol Microparticles (Dermalix) and Standard Wound Care for Diabetic Foot Ulcers.
This is an open, prospective, comparative parallel-arm medical device clinical study of Dermalix (Dx) in diabetic foot wounds. Dx is a 3-dimensional collagen-laminin porous-structured dermal matrix prepared and additionally impregnated with resveratrol-loaded hyaluronic acid and dipalmitoylphosphatidylcholine-based microparticles. The aim was to evaluate the efficacy and safety of Dx, an investigational medical device, in Wagner 1 and 2 wounds in comparison to a standard wound care (SWC) that consists of irrigation and cleaning with sterile saline solution. Forty-eight patients were randomized to receive either SWC or SWC + Dx. A 4-week treatment period was followed by a 2-month follow-up without treatment. The wound area measurement, total collagen, vascular epidermal growth factor, tumor necrosis factor, interleukin 1, caspase 3, glutathione, reduced/oxidized glutathione, and lipid peroxidation levels were evaluated. At the end of 4 weeks, the percentage closures of wounds were determined as 57.82% for Dx, and 26.63% for SWC groups. Dx had a significant effect on tumor necrosis factor, caspase 3, and reduced/oxidized glutathione levels. Dx provided 2 times faster wound healing and decreased oxidative stress. Application of Dx in the first phase of wound would help the wound area heal faster with a safe profile.


Effect of Lipoxygenase Oxidation on Surface Deposition of Unsaturated Fatty Acids.
We studied the interactions of lipid molecules (linoleic acid, glycerol trilinoleate and a complex mixture of wood extractives) with hydrophilic and hydrophobic surfaces (cellulose nanofibrils (CNFs) and polyethylene terephthalate (PET), respectively). The effect of lipoxygenase treatment to minimize the affinity of the lipids with the given surface was considered. Application of an electroacoustic sensing technique (QCM) allowed the monitoring of the kinetics of oxidation as well as dynamics of lipid deposition on CNF and PET. The effect of the lipoxygenase enzymes (LOX) was elucidated with regards to their ability to reduce the formation of soiling lipid layers. The results pointed to the fact that the rate of colloidal oxidation depended on the type of lipid substrate. The pretreatment of the lipids with LOX reduced substantially their affinity to the surfaces, especially PET. Surface plasmon resonance (SPR) sensograms confirmed the effect of oxidation in decreasing the extent of deposition on the hydrophilic CNF. QCM energy dissipation analyses revealed the possible presence of a loosely adsorbed lipid layer on the PET surface. The morphology of the deposits accumulated on the solids was determined by atomic force microscopy and indicated important changes upon lipid treatment with LOX. The results highlighted the benefit of enzyme as a biobased treatment to reduce hydrophobic interactions, thus providing a viable solution to the control of lipid deposition from aqueous media.


Interactions of dietary methionine, lead and lindane in rats.
The effects of dietary methionine on lead and lindane toxicities in rats were studied in two experiments. Rats were fed methionine-deficient (60% of requirement) or methionine-sufficient soy protein-based diets with lead acetate added (10,000 mg/kg Pb) and treated with a single dose of lindane (25% of LD50 or 88 mg/kg, p.o.) in both experiments. In experiment I, all rats were fed ad libitum. In experiment II, rats fed the methionine-sufficient diet were pair-fed to rats fed the methionine-deficient diet. In experiments I and II, the methionine-sufficient and the methionine-deficient rats had decreased final body weights, increased liver weights, decreased hematocrits, and no changes in glutathione S-transferase activity when compared to a control group. Lead + lindane treatments increased liver glutathione levels in the methionine-sufficient and methionine-deficient rats in both experiments. However, in experiment II (pair-feeding), the methionine-sufficient rats had a much greater level of liver glutathione than the methionine-deficient rats. The methionine status of the animals seems to be an important factor in determining the liver glutathione level of pair-fed rats treated with lead + lindane.


Decreased Expression of Vascular Endothelial Growth Factor Receptor 1 Contributes to the Pathogenesis of Hereditary Hemorrhagic Telangiectasia Type 2.
Hereditary Hemorrhagic Telangiectasia type 2 (HHT2) is an inherited genetic disorder characterized by vascular malformations and hemorrhage. HHT2 results from ACVRL1 haploinsufficiency, the remaining wild-type allele being unable to contribute sufficient protein to sustain endothelial cell function. Blood vessels function normally but are prone to respond to angiogenic stimuli, leading to the development of telangiectasic lesions that can bleed. How ACVRL1 haploinsufficiency leads to pathological angiogenesis is unknown. We took advantage of Acvrl1+/- mutant mice that exhibit HHT2 vascular lesions and focused on the neonatal retina and the airway system after Mycoplasma pulmonis infection, as physiological and pathological models of angiogenesis, respectively. We elucidated underlying disease mechanisms in vitro by generating Acvrl1+/- mouse embryonic stem cell lines that underwent sprouting angiogenesis and performed genetic complementation experiments. Finally, HHT2 plasma samples and skin biopsies were analyzed to determine whether the mechanisms evident in mice are conserved in humans. Acvrl1+/- retinas at postnatal day 7 showed excessive angiogenesis and numerous endothelial "tip cells" at the vascular front that displayed migratory defects. Vascular endothelial growth factor receptor 1 (VEGFR1; Flt-1) levels were reduced in Acvrl1+/- mice and HHT2 patients, suggesting similar mechanisms in humans. In sprouting angiogenesis, VEGFR1 is expressed in stalk cells to inhibit VEGFR2 (Flk-1, KDR) signaling and thus limit tip cell formation. Soluble VEGFR1 (sVEGFR1) is also secreted, creating a VEGF gradient that promotes orientated sprout migration. Acvrl1+/- embryonic stem cell lines recapitulated the vascular anomalies in Acvrl1+/- (HHT2) mice. Genetic insertion of either the membrane or soluble form of VEGFR1 into the ROSA26 locus of Acvrl1+/- embryonic stem cell lines prevented the vascular anomalies, suggesting that high VEGFR2 activity in Acvrl1+/- endothelial cells induces HHT2 vascular anomalies. To confirm our hypothesis, Acvrl1+/- mice were infected by Mycoplasma pulmonis to induce sustained airway inflammation. Infected Acvrl1+/- tracheas showed excessive angiogenesis with the formation of multiple telangiectases, vascular defects that were prevented by VEGFR2 blocking antibodies. Our findings demonstrate a key role of VEGFR1 in HHT2 pathogenesis and provide mechanisms explaining why HHT2 blood vessels respond abnormally to angiogenic signals. This supports the case for using anti-VEGF therapy in HHT2.


Impaired memory retention and decreased long-term potentiation in integrin-associated protein-deficient mice.
Previously, we have demonstrated that integrin-associated protein (IAP) mRNA level is approximately fourfold higher in rats showing good retention performance (600 sec) than rats showing poor retention performance (< 80 sec) in an inhibitory avoidance learning paradigm. In the present study, we have used the gene-targeted IAP-deficient mice to further investigate the role of IAP involved in memory formation and hippocampal long-term potentiation (LTP) in vivo. Results revealed that there was a significant impairment in memory retention and a significant reduction in the magnitude of LTP in IAP-deficient mice when compared with the wild-type and heterozygote mice, whereas the wild-type and heterozygote animals did not show marked differences on these measures. Furthermore, the impairment in retention performance of IAP-deficient mice was not due to different sensitivities of these animals to the electric shock. When we examined locomotor activity and rotarod treadmill performance, no differences were observed among these three groups of animals either. Western blot analysis confirmed the lack of IAP protein in IAP-deficient mice, whereas IAP expression was similar in both the wild-type and heterozygote controls. These results together demonstrate that IAP plays an important role in the process of memory formation and synaptic plasticity in mice.


Low back stability: from formal description to issues for performance and rehabilitation.
Low back stability: from formal description to issues for performance and rehabilitation. Exerc. Sport Sci. Rev. Vol. 29, No. 1, pp. 26-31, 2001. The concept of stability, together with notions of design and the application of stabilization exercise, is briefly synthesized. The objective is to challenge muscle systems to achieve sufficient functional stability but in a way that spares the spine of excessive exacerbating load.


Regulation of renal phosphate transport by FGF23 is mediated by FGFR1 and FGFR4.
Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that acts on the proximal tubule to decrease phosphate reabsorption and serum levels of 1,25-dihydroxyvitamin D₃ [1,25(OH)₂ Vitamin D₃]. Abnormal FGF23 metabolism has been implicated in several debilitating hypophosphatemic and hyperphosphatemic disorders. The renal receptors responsible for the phosphaturic actions of FGF23 have not been elucidated. There are four fibroblast growth factor receptors (FGFR); 1-4 with "b" and "c" isoforms for receptors 1, 2, and 3. FGFR1, 3, and 4 are expressed in the mouse proximal tubule, and deletion of any one receptor did not affect serum phosphate levels, suggesting that more than one receptor is involved in mediating the phosphaturic actions of FGF23. To determine the receptors responsible for the phosphaturic actions of FGF23, we studied Fgfr1 (kidney conditional) and Fgfr4 (global) double mutant mice (Fgfr1⁻/⁻/Fgfr4⁻/⁻). Fgfr1⁻/⁻/Fgfr4⁻/⁻ mice have higher FGF23 levels than their wild-type counterparts (108.1 ± 7.3 vs. 4,953.6 ± 675.0 pg/ml; P < 0.001). Despite the elevated FGF23 levels, Fgfr1⁻/⁻/Fgfr4⁻/⁻ mice have elevated serum phosphorus levels, increased brush-border membrane vesicle (BBMV) phosphate transport, and increased Na-P(i) cotransporter 2c (NaPi-2c) protein expression compared with wild-type mice. These data are consistent with FGFR1 and FGFR4 being the critical receptors for the phosphaturic actions of FGF23.


Characterization of cell-free protein-synthesis systems from undeveloped and developing Artemia embryos.
We have developed and characterized translationally active cell-free systems from Artemia embryos at different developmental times. The optimized lysates from 16 h-developed embryos incorporated radiolabelled amino acids into polypeptides for up to 120 min. The polypeptides synthesized ranged in Mr from 150,000 to 10,000, suggesting that the endogenous mRNA was capable of directing the synthesis of complete polypeptides. Similar results were obtained by using lysates from early developmental stages; even the cell-free system prepared from 1 h-developed embryos was partially active in protein synthesis. Furthermore, all these lysates were capable of re-initiation, as demonstrated by inhibition of initiation with the inhibitors edeine and 7-methylguanosine 5'-triphosphate. Because we found no endogenous protein-synthetic activity in the corresponding lysates from undeveloped embryos, we have used cell-free translation systems from 0 h- and 16 h-developed Artemia embryos to analyse the mechanisms limiting protein synthesis at very early developmental stages. Undeveloped-embryo lysates supplemented with nuclease-treated reticulocyte lysate were capable of translating endogenous mRNAs to give products with a wide spectrum of Mr values, but lysates of 16 h-developed embryos supplemented in this way were not further stimulated. The nuclease-treated lysate appeared to be unnecessary 5 h after resumption of development. These results suggested that a component(s) limiting translation in the undeveloped-embryo lysate was provided by the nuclease-treated reticulocyte lysate, and that this component(s) no longer limited protein synthesis after development. In view of these results, partially fractionated reticulocyte lysates were tested for restoration of protein-synthetic activity in the undeveloped embryo lysate. A high-salt ribosomal wash devoid of ribosomal subunits, which is considered a crude polypeptide-initiation-factor preparation, also restored translation activity in the undeveloped embryo lysate and made it capable of directing the synthesis of both endogenous mRNAs and exogenous (globin) mRNA.


Asthma care practices, perceptions, and beliefs of Chicago-area asthma specialists. Chicago Asthma Surveillance Initiative Project Team.
Few studies have closely explored how well physicians who consider themselves specialists in asthma adhere to national guideline recommendations for the diagnosis and treatment of asthma. The purpose of this study is to characterize current knowledge, attitudes, beliefs, and self-reported treatment practices of the asthma specialists working in one large metropolitan area. In 1997, a cross-sectional survey was mailed to asthma specialists (allergists or pulmonologists) engaged in direct patient care with a practice location in the Chicago area (Cook County or one of the five surrounding counties). An approximately 50% random sample of asthma specialists was surveyed. The survey included items on (1) asthma diagnosis; (2) clinical monitoring of asthma patients; (3) pharmacologic and nonpharmacologic asthma treatment; (4) opinions and beliefs about asthma treatment options and reasons for referrals; (5) involvement in continuing medical education; (6) experiences with managed care; (7) use of asthma practice guidelines; (8) demographic information about the respondents; and (9) characteristics of the practice settings. A total of 113 eligible surveys were returned (response rate, 72.0%). Ninety-nine percent of the respondents indicated they would prescribe inhaled corticosteroids for patients > or = 5 years old with moderate persistent asthma, and 85.5% would prescribe them for patients < 5 years old. The respondents reported that 71.2% of their patients with moderate or severe persistent asthma were routinely given written treatment plans. The use of these plans was reported more frequently by allergists than pulmonologists (77.6% vs 58.9%, p = 0.01). Nearly half of the respondents were involved in the development of hospital-based asthma programs; fewer (14.9%) were involved in developing asthma programs for managed care organizations. A majority (63.4%) of the physicians had given a formal professional education presentation on asthma in the past year. A majority of the respondents who care for patients under managed care contracts reported that these patients have encountered barriers to access in seeking specialty care. The results suggest that asthma specialists in the Chicago area are providing asthma care that is, in many ways, consistent with national guidelines. However, there are also important differences in care that are not consistent with the guideline recommendations. Perhaps even more notable are differences in reported asthma care between the two subspecialty groups of allergists and pulmonologists. The effect of these differences on the management of persons with asthma is not known. It is hoped that information from this community-based survey will serve to catalyze discussions among Chicago-area asthma specialists as to how they might envision improving care for persons with asthma in their community.


The Plasminogen Activation System Promotes Neurorepair in the Ischemic Brain.
The plasminogen activation (PA) system was originally thought to exclusively promote the degradation of fibrin by catalyzing the conversion of plasminogen into plasmin via two serine proteinases: tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). However, experimental evidence accumulated over the last 30 years indicates that tPA and uPA are also found in the central nervous system (CNS), where they have a plethora of functions that not always require plasmin generation or fibrin degradation. For example, plasminogen-dependent and - independent effects of tPA and uPA play a central role in the pathophysiological events that underlie one of the leading causes of mortality and disability in the world: cerebral ischemia. Indeed, recent work indicates that while the rapid release of tPA from the presynaptic compartment following the onset of cerebral ischemia protects the synapse from the deleterious effects of the ischemic injury, the secretion of uPA and its binding to its receptor (uPAR) during the recovery phase promotes the repair of synapses that have been lost to the acute ischemic insult. This restorative role of uPA has high translational significance because to this date there is no effective approach to induce neurorepair in the ischemic brain. Here we will discuss recent evidence that bridges the gap between basic research in the field of the PA system and the bedside of ischemic stroke patients, indicating that uPA and uPAR are potential targets for the development of therapeutic strategies to promote neurological recovery among ischemic stroke survivors.


Endodontic management of the avulsed tooth and tooth transplantation.
The major causes of post-transplantation tooth loss following tooth replacement after avulsion (exarticulation) and surgical replacement of impacted maxillary canines (auto-transplantation) are inflammatory root resorption and replacement resorption (ankylosis). This paper attempts to outline the treatment and management of replanted teeth using the current philosophies of splinting, endodontic therapy and the use of calcium hydroxide in the re-attachment of the periodontal ligament (PDL). Clinical research during the past 20 years has provided sufficient information for the development and establishment of a rational and effective program of treatment.


Rheologic characterization of vegetal lectins by dissociation of induced erythrocyte agglutinates.
Energy evolved from hemagglutination reaction or spent in dissociating erythrocyte agglutinates has been proved to be an excellent parameter for analyzing cell-cell interactions mediated by bridging molecules such as antibodies or lectins. We developed a new rheo-optical method to estimate the energy of dissociation of red blood cell agglutinates. In a Couette shear field agglutinates can be dissociated until a suspension of monodispersed cells is obtained. Intensity of light backscattered by suspended agglutinates increases during their mechanical dissociation. Variation of backscattered light intensity correlates with the energy spent in the process. The adhesive energy of erythrocyte agglutination induced by lectins has been estimated by applying this method. Two specific lectins (Dolichus Biflorus agglutinin and Ulex Europaeus agglutinin) and a new lectin obtained from Amarantus Cruentus seeds which specificity is unknown were studied. Results obtained in this work for Dolichus Biflorus lectin are comparable with values published by other authors. An asymptotic decrease of adhesive energy was observed when the mechanical dissociation was applied several times on the same sample. Our results suggest that the cell detachment is accompanied by the extraction of membrane receptors. This finding is consistent with results obtained by other authors.


COVID-19 Antibody Testing as a Precondition for Employment: Ethical and Legal Considerations.
Employers and governments are interested in the use of serological (antibody) testing to allow people to return to work before there is a vaccine for SARS-CoV-2. We articulate the preconditions needed for the implementation of antibody testing, including the role of the U.S. Food & Drug Administration.


Oxidative Stress and Antioxidant Defense Mechanisms in Acute Ischemic Stroke Patients with Concurrent COVID-19 Infection.
Stroke remains a debilitating cerebrovascular condition associated with oxidative stress, while COVID-19 has emerged as a global health crisis with multifaceted systemic implications. This study investigates the hypothesis that patients experiencing acute ischemic stroke alongside COVID-19 exhibit elevated oxidative stress markers and altered antioxidant defense mechanisms compared to those with acute ischemic stroke. We conducted a single-center prospective cross-sectional study to investigate oxidative stress balance through oxidative damage markers: TBARS (thiobarbituric acid reactive substances level) and PCARB (protein carbonyls); antioxidant defense mechanisms: TAC (total antioxidant capacity), GPx (glutathione peroxidase), GSH (reduced glutathione), CAT (catalase), and SOD (superoxide dismutase); as well as inflammatory response markers: NLR (neutrophil-to-lymphocyte ratio), CRP (C-reactive protein), and ESR (erythrocyte sedimentation rate). Statistical analyses and correlation models were employed to elucidate potential associations and predictive factors. Our results revealed increased oxidative stress, predominantly indicated by elevated levels of TBARS in individuals experiencing ischemic stroke alongside a concurrent COVID-19 infection (p < 0.0001). The Stroke-COVID group displayed notably elevated levels of GSH (p = 0.0139 *), GPx (p < 0.0001 ****), SOD (p = 0.0363 *), and CAT (p = 0.0237 *) activities. Multivariate analysis found a significant association for TBARS (p < 0.0001 ****), PCARB (p = 0.0259 *), and GPx activity (p < 0.0001 ****), together with NLR (p = 0.0220 *) and CRP (p = 0.0008 ***). Notably, the interplay between stroke and COVID-19 infection appears to amplify oxidative damage, potentially contributing to exacerbated neurological deficits and poorer outcomes. This study highlights the intricate relationship between oxidative stress, inflammation, and concurrent health conditions. Understanding these interactions may open avenues for novel therapeutic strategies aimed at ameliorating oxidative damage in patients with acute ischemic stroke and COVID-19, ultimately improving their prognosis and quality of life.


IL-12/IL-12R system in multiple sclerosis.
IL-12/IL-12 receptor (IL-12R) system orchestrates the Th1 pathway of the immune system by maintaining one of the major bridges between innate and adaptive immune responses. Here, we studied both sides of this system in patients with multiple sclerosis (MS) and in controls. MS patients displayed elevated IL-12Rbeta1 and IL-12Rbeta2 expression on PHA-activated T cells compared to healthy subjects. Higher percentages of IL-12Rbeta1 and IL-12Rbeta2 positive T cells in cerebrospinal fluid (CSF) compared to blood were observed both in MS and other neurological diseases (OND). In contrast, numbers of IL-12 secreting blood mononuclear cells (MNC) were similar in MS and controls. The functional importance of high IL-12Rbeta2 in MS was underlined by the finding that IL-12 stimulated IFN-gamma production and proliferation of PHA-activated T cells correlated with levels of IL-12Rbeta2 expression. Our data indicates a dysregulation of the IL-12/IL-12R system in MS. It is suggested that even in the absence of increased IL-12 levels, the net effect of IL-12 might be augmented in MS by elevated expression of its receptor.


Dynamics of one- and two-dimensional fronts in a bistable equation with time-delayed global feedback: Propagation failure and control mechanisms.
We study the evolution of fronts in a bistable equation with time-delayed global feedback in the fast reaction and slow diffusion regime. This equation generalizes the Hodgkin-Grafstein and Allen-Cahn equations. We derive a nonlinear equation governing the motion of fronts, which includes a term with delay. In the one-dimensional case this equation is linear. We study the motion of one- and two-dimensional fronts, finding a much richer dynamics than for the previously studied cases (without time-delayed global feedback). We explain the mechanism by which localized fronts created by inhibitory global coupling loose stability in a Hopf bifurcation as the delay time increases. We show that for certain delay times, the prevailing phase is different from that corresponding to the system in the absence of global coupling. Numerical simulations of the partial differential equation are in agreement with the analytical predictions.


The cutting edge-an investigation into the pressure necessary for cutting skin with different knife blade types.
Sharp force trauma is routinely encountered in forensic practice. Often the question is posed, how much pressure or energy would have been necessary to inflict a cut with a specific knife, in order to further characterize the perpetrator or determine his intent to cause harm. This paper investigates two knife blades and its individual pressures needed to cut through the epidermis and dermis. In order to examine the necessary force for cutting through the skin, we performed experiments on a piglet skin-on-gelatin phantom. Two similarly small knives-a paring knife with a serrated blade and a Swiss Army pocket knife with a smooth blade-were moved over the phantom surface using a mobile cutting apparatus with varying weight on the load arm with the knife. The depth of the cut was to be determined according to a scale from zero to three: grade 0 = no cut; grade 1 = cut into epidermis only; grade 2 = cut into dermis; grade 3 = complete transection of the entire skin. Each cut inflicted at a specific pressure force was assessed closely in order to ascertain depth, calculate the velocity, and ultimately determine the point at which a cut would inflict grade 3 damage. The smooth blade of a pocket knife needed at least 1900g pressure in order to slice through pig skin mounted on a thick gelatin block, whereas a serrated blade of a paring knife managed to cut into or through the dermis at a comparatively lower force of 700g. Our study shows that at the same cutting velocity, a significant difference in pressure is necessary to inflict the same degree of damage.


[Function of REM sleep].
The author gives a review of the biological and psychological functions ascribed to paradoxical sleep. Most of the investigative work in the field has been dedicated to proving a relationship between REM sleep and learning. For intellectual learning the evidence is inconclusive, whereas there do seem to exist some ties between REM time and emotional learning. REM sleep functioning should not be viewed separately from the functions of NREM sleep and the waking state.


[On the necessity to prepare new "Rules for the organization and conduction of forensic biological examination and studies by the State Forensic Examination Boards of the Russian Federation"].
The author substantiates the necessity to prepare new "Rules for the organization and conduction of forensic biological examination and studies by the State Forensic Examination Boards of the Russian Federation". Their long-term absence of the reviewed document has negatively influenced the quality of work of these facilities. The structure and contents of the three previous versions of the Rules for the study of material evidence (1934, 1956, and 1996) are analysed. The structure of the new variant is designed to optimize the work of forensic medical examination bureaus and the performance of relevant studies.


Avellino corneal dystrophy worsening after laser in situ keratomileusis: further clinicopathologic observations and proposed pathogenesis.
To study the nature of the deposits in Avellino corneal dystrophy (ACD) worsening after laser in situ keratomileusis (LASIK), and suggest a mechanism for histopathogenesis. Interventional case report. A 28-year-old woman previously diagnosed with bilateral ACD underwent bilateral LASIK. The corneal dystrophy progressively worsened bilaterally, one year later. A penetrating keratoplasty was subsequently performed on the right eye at 31 years of age, and in the left eye a year later. The clinical and histopathologic findings of the corneal graft of the right eye were reported in the literature, with positivity to the Masson trichrome stain, negative staining with Congo red, and heterozygosity for the Arg124His mutation by serum DNA studies. Histopathologic studies of the corneal graft of the left eye were conducted at the University of Texas Southwestern Medical Center. Histopathologic examination of the excised cornea showed the Masson trichrome positive deposits present from underneath the Bowman layer to the LASIK interface, with absence of deposits posterior to the latter. In contrast to the prior report describing findings in the corneal graft of the left eye, the deposits stained lightly with Congo red, but failed to show birefringence under polarized light, or fluorescence with thioflavin T. Accelerated deposits developing after LASIK in ACD eyes seem to harbor pre-amyloid features. The epithelium is likely to be the culprit, in a pathway independent of with human transforming growth hormone beta (TGF-beta), with deposits developing in the anterior stroma and the stromal interface.


New insights into the HCV quasispecies and compartmentalization.
Hepatitis C virus (HCV) is a hepatotropic RNA virus with an extraordinary propensity to persist in the vast majority of infected individuals. During replication, because of the inherent infidelity of the viral RNA polymerase, each progeny RNA genome contains mutations that lead to a continuous diversification of the viral population. Consequently, HCV circulates in vivo as a quasispecies, which is a dynamic distribution of divergent but closely related genomes subjected to a continuous process of genetic variation, competition, and selection. This genomic heterogeneity confers a remarkable advantage to the viral population allowing for a rapid adaptation to a changing environment when the virus is subject to selective constraints exerted by the host, such as antiviral immunity, or external to the host, such as antiviral therapy. The large reservoir of variants provided by the quasispecies represents a great challenge for the control of HCV infection and has important biologic implications for viral persistence, host cell tropism, antiviral drug resistance, and development of an HCV vaccine. This review discusses the molecular mechanisms of HCV genetic variation and the biologic and clinical relevance of the quasispecies nature of HCV.


Impact of minimally invasive surgery in the treatment of esophageal cancer.
Surgical treatment of esophageal cancer is associated to a high morbidity and mortality rate. The open transthoracic or transhiatal esophagectomy are considerably invasive procedures and have been associated to high rates of complications and operative mortality. In this way, minimally invasive esophageal surgery has been suggested as an alternative to the classic procedures because would produce improvement in clinical longterm postoperative outcomes. To assess survival, mortality and morbidity results of esophagectomy due to esophageal cancer submitted to minimally invasive techniques and compare them to results published in international literature. An observational, prospective study. Between 2003 and 2012, 69 patients were submitted to a minimally invasive esophagectomy due to cancer. It was recorded postoperative morbidity and mortality according to the Clavien-Dindo classification. The survival rate was analyzed with the Kaplan-Meier method. The number of lymph nodes obtained during the lymph node dissection, as an index of the quality of the surgical technique, was analysed. 63.7% of patients had minor complications (type I-II Clavien Dindo), while nine (13%) required surgical re-exploration. The most common postoperative complication corresponded to leak of the cervical anastomosis seen in 44 (63.7%) patients but without clinical repercusion, only two of them required reoperation. The mortality rate was 4.34%, and reoperation was necessary in nine (13%) cases. The average survival time was 22.59 ± 25.38 months, with the probability of a 3-year survival rate estimated at 30%. The number of resected lymph nodes was 17.17 ± 9.62. Minimally invasive techniques have lower morbidity and mortality rate, very satisfactory lymphnodes resection and similar long term outcomes in term of quality of life and survival compared to results observed after open surgery.


Successful management of aortoiliac aneurysms with a quadrifurcated prosthesis.
Aortoiliac aneurysms constitute one of the main challenges facing vascular surgeons worldwide. We report for the first time the successful reconstruction of the aorta and iliac arteries with a quadrifurcated prosthesis, in a 72-year-old man with an infrarenal abdominal aortic aneurysm, and aneurysms of the iliac arteries involving both iliac bifurcations. The aortoiliac reconstruction was performed with a quadrifurcated knitted Dacron graft, revascularising both internal and external iliac arteries. In our opinion, the use of such a graft is recommended in aortoiliac revascularisations whenever it is advisable for the preservation of flow to internal iliac arteries.


Expanding proteome coverage with orthogonal-specificity α-lytic proteases.
Bottom-up proteomics studies traditionally involve proteome digestion with a single protease, trypsin. However, trypsin alone does not generate peptides that encompass the entire proteome. Alternative proteases have been explored, but most have specificity for charged amino acid side chains. Therefore, additional proteases that improve proteome coverage through cleavage at sequences complementary to trypsin's may increase proteome coverage. We demonstrate the novel application of two proteases for bottom-up proteomics: wild type α-lytic protease (WaLP) and an active site mutant of WaLP, M190A α-lytic protease (MaLP). We assess several relevant factors, including MS/MS fragmentation, peptide length, peptide yield, and protease specificity. When data from separate digestions with trypsin, LysC, WaLP, and MaLP were combined, proteome coverage was increased by 101% relative to that achieved with trypsin digestion alone. To demonstrate how the gained sequence coverage can yield additional post-translational modification information, we show the identification of a number of novel phosphorylation sites in the Schizosaccharomyces pombe proteome and include an illustrative example from the protein MPD2 wherein two novel sites are identified, one in a tryptic peptide too short to identify and the other in a sequence devoid of tryptic sites. The specificity of WaLP and MaLP for aliphatic amino acid side chains was particularly valuable for coverage of membrane protein sequences, which increased 350% when the data from trypsin, LysC, WaLP, and MaLP were combined.


Prosthetic Management of a Nasal Septal Defect using a Custom Made Unilateral Intranasal Stent: A Case Report.
Various etiologies including congenital malformations, infections, trauma, iatrogenic causes or complications of systemic diseases can result in perforation of the nasal septum. The common symptoms associated with such defects include difficulty in breathing, nasal twang in voice, rhinorrhea, etc. Obturation can be achieved by insertion of a unilateral nasal stent. An attempt has been made in the present report to address the prosthetic management of pateint having nasal septum perforation utilizing a unilateral, custom made heat cured acrylic stent and the details of the technique are presented.


The effect of GHRH antagonists on human glioblastomas and their mechanism of action.
The effects of new growth hormone-releasing hormone (GHRH) antagonists JMR-132 and MIA-602 and their mechanism of action were investigated on 2 human glioblastoma cell lines, DBTRG-05 and U-87MG, in vitro and in vivo. GHRH receptors and their main splice variant, SV1 were found on both cell lines. After treatment with JMR-132 or MIA-602, the cell viability decreased significantly. A major decrease in the levels of phospho-Akt, phospho-GSK3β and phosho-ERK 1/2 was detected at 5 and 10 min following treatment with the GHRH antagonists, whereas elevated levels of phospho-p38 were observed at 24 hr. The expression of caspase-3 and poly(ADP-ribose) (PARP), as the downstream executioners of apoptosis were found to be significantly elevated after treatment. Following treatment of the glioblastoma cells with GHRH antagonists, nuclear translocation of apoptosis inducing factor (AIF) and Endonuclease G (Endo G) and the mitochondrial release of cytochrome c (cyt c) were detected, indicating that the cells were undergoing apoptosis. In cells treated with GHRH antagonists, the collapse of the mitochondrial membrane potential was shown with fluorescence microscopy and JC-1 membrane potential sensitive dye. There were no significant differences between results obtained in DBTRG-05 or U-87MG cell lines. After treatment with MIA-602 and JMR-132, the reduction rate in the growth of DBTRG-05 glioblastoma, xenografted into nude mice, was significant and tumor doubling time was also significantly extended when compared with controls. Our study demonstrates that GHRH antagonists induce apoptosis through key proapoptotic pathways and shows the efficacy of MIA-602 for experimental treatment of glioblastoma.


The effect of vasopressin on ciliary blood flow and aqueous flow.
Previous experiments have shown that arginine-vasopressin (AVP) reduces intraocular pressure (IOP) dose-dependently. The present study investigated the relationships between IOP, ciliary blood flow (CilBF), and aqueous flow (AqF) responses to AVP in anesthetized rabbits. CilBF was measured by laser Doppler flowmetry and AqF by fluorophotometry. Mean arterial pressure (MAP) and IOP were monitored continuously and simultaneously. Perfusion pressure (PP) was varied mechanically. Four experimental protocols were performed: the dose-response (n = 11) and the pressure-flow relationship (n = 8) for CilBF and the effects on CilBF, and AqF at low (0.08 ng/kg/min; n = 14) and high AVP infusion rates (1.33 ng/kg/min; n = 12). AVP decreased CilBF and IOP dose-dependently. At the low AVP infusion rate, AqF was reduced by 21.48% ± 2.52% without changing CilBF significantly. The high AVP infusion rate caused a 24.49% ± 3.53% decrease of AqF and a significant reduction in CilBF (35.60% ± 3.58%). IOP was reduced by 9.56% ± 2.35% at low and by 41.02% ± 3.19% at high AVP infusion rates. Based on the Goldmann equation, the decrease of AqF at the low AVP infusion rate accounted for 77.1% of the IOP reduction, whereas at the high AVP infusion rate, decreased AqF accounted for 28.4% of the IOP decline. The results indicate that AVP can modulate IOP by different dose-dependent physiological mechanisms. The shifts of the CilBF-AqF relationship suggest that the reduction of AqF by the low AVP infusion rate is mainly provoked by inhibiting secretory processes in the ciliary epithelium. In contrast, at the high AVP infusion rate, the AqF reduction is caused by either reduced CilBF or more likely by a combined effect of reduced CilBF and secretory inhibition.


Correlation of Corneal Biomechanical Stiffness With Refractive Error and Ocular Biometry in a Pediatric Population.
To assess the correlation between corneal biomechanical stiffness and refractive error (RE) in the pediatric population. A total of 733 pediatric eyes were included in the study retrospectively. All eyes underwent corneal tomography (Pentacam), RE assessment, and air-puff deformation (Corvis-ST). Waveform analyses of deformation provided corneal stiffness (CS) and extraocular tissue stiffness (EOS). Eyes were subgrouped into emmetropia [manifest refraction spherical equivalent (MRSE) ∼ 0 D], hyperopia (MRSE > 0 D), myopia I (MRSE between 0 D and -3 D), myopia II (MRSE between -3 D and -6 D), and myopia III (MRSE greater than -6 D) for multivariate analyses. Ocular biometry variables [age, intraocular pressure (IOP), central corneal thickness (CCT), corneal astigmatism, anterior chamber depth, and RE] were used as covariates. The apparent elastic modulus (E) was defined as the ratio of CS and CCT. All groups had similar age, CCT, and IOP (P > 0.05). CS was the only parameter to differ between all the grades of myopia (P < 0.0001). CS was lower by 3.72%, 6.84%, and 10.68% in myopia I, II, and III eyes, respectively, relative to emmetropic eyes. EOS increased by 11.15%, 22.60%, and 28.5%, respectively. Multivariate regression revealed age, IOP, CCT, corneal astigmatism, anterior chamber depth, and RE as significant predictors of CS, with a high coefficient of regression (R = 0.66). Corneal E negatively correlated with the grade of myopia. CS and EOS correlated negatively and positively with the grade of myopia, respectively. Ocular biometry variables were significant predictors of both CS and EOS. The decrease in CS was attributed to that in elastic modulus.


Use of PCR and sodium dodecyl sulfate-polyacrylamide gel electrophoresis techniques for differentiation of Prevotella intermedia sensu stricto and Prevotella nigrescens.
Primers were designed from 16S rRNA sequences of Prevotella intermedia sensu stricto and Prevotella nigrescens and were used to discriminate these two species by PCR. The results were compared with those from the PCR technique using primers designed from arbitrarily primed PCR products by Guillot and Mouton (E. Guillot and C. Mouton, J. Clin. Microbiol. 35:1876-1882, 1997). The specificities of both assays were studied by using P. intermedia ATCC 25611, P. nigrescens ATCC 33563, 174 clinical isolates of P. intermedia sensu lato, and 59 reference strains and 58 clinical isolates of other Prevotella species and/or common oral flora. In addition, the usefulness and reliability of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the differentiation of the two species were examined by comparing the results with those from PCR assays. The controversial lipase test for distinguishing these species was also carried out. Unambiguous differentiation was made by both PCR assays, and the results matched each other. The SDS-PAGE assay was found to misidentify a few strains tested, compared with the results of PCR assays. The lipase test was positive for both species, including the reference strains of P. intermedia and P. nigrescens. We conclude that both PCR assays are simple, rapid, reliable, and specific methods which could be used in clinical studies and that the lipase test is not valuable in the differentiation. The reliable discrimination of the two species by SDS-PAGE is questionable.


Axonal stimulation for end-plate jitter studies.
This single fibre EMG study compares the standard method of neuromuscular jitter measurement in voluntarily activated muscle to that by intramuscular electrical stimulation of motor axons in a group of normal subjects. The latter method avoids the interdischarge interval-dependent jitter, as well as a possible failure to recognise split muscle fibres. The mean MCD on axonal stimulation was only 5.2 microseconds less than in the voluntary activation study and was thus 8% more than theoretically expected for single motor end plates. The difference could be due to an axonal jitter and some other factors. Axonal stimulation has proved to be a relatively easy and reliable method for routine estimation of neuromuscular jitter, provided that the resolution of time measurement is better than 2 microseconds, so that low jitter due to occasional direct muscle fibre stimulation is not mistaken for a normal reading. The upper normal limits for the extensor digitorum communis muscle suggested by the present study are 40 microseconds (individual muscle fibres) and 25 microseconds (mean of 30 muscle fibres).


Failure of the cystic fibrosis transmembrane conductance regulator to conduct ATP.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion channel regulated by protein kinase A and adenosine triphosphate (ATP). Loss of CFTR-mediated chloride ion conductance from the apical plasma membrane of epithelial cells is a primary physiological lesion in cystic fibrosis. CFTR has also been suggested to function an an ATP channel, although the size of the ATP anion is much larger than the estimated size of the CFTR pore. ATP was not conducted through CFTR in intact organs, polarized human lung cell lines, stably transfected mammalian cell lines, or planar lipid bilayers reconstituted with CFTR protein. These findings suggest that ATP permeation through the CFTR is unlikely to contribute to the normal function of CFTR or to the pathogenesis of cystic fibrosis.


Identification of 26RFa, a hypothalamic neuropeptide of the RFamide peptide family with orexigenic activity.
A neuropeptide was isolated from a frog brain extract by HPLC purification and characterized by mass spectrometry. This 26-aa neuropeptide, which belongs to the RFamide peptide family, was designated 26RFa, and its primary structure was established as VGTALGSLAEELNGYNRKKGGFSFRF-NH2. Research in databases revealed the presence of sequences homologous to frog 26RFa in the human genome and in rat ESTs. On the basis of this sequence information, the cDNAs encoding the human and rat 26RFa precursors were cloned. The two preproteins show a similar organization, with the 26RFa sequence located in the C-terminal region of the precursor. Human preprotein (prepro)-26RFa encodes an additional putative RFamide peptide that is not found in the rat precursor. The primary structures of human, rat, and frog 26RFa exhibit approximately 80% identity, and the C-terminal octapeptide has been fully conserved from amphibians to mammals. In situ hybridization histochemistry revealed that, in the rat brain, the 26RFa gene is exclusively expressed in the ventromedial hypothalamic nucleus and in the lateral hypothalamic area. 26RFa induced a dose-dependent stimulation in cAMP production by rat pituitary cells in vitro and markedly increased food intake in mice. The conservation of the primary structure of 26RFa during vertebrate evolution, the discrete localization of the mRNA encoding its precursor in hypothalamic nuclei involved in the control of feeding behavior, and the observation that 26RFa possesses orexigenic properties indicate that this neuropeptide may play important biological functions.


Brain correlates of stuttering and syllable production. A PET performance-correlation analysis.
To distinguish the neural systems of normal speech from those of stuttering, PET images of brain blood flow were probed (correlated voxel-wise) with per-trial speech-behaviour scores obtained during PET imaging. Two cohorts were studied: 10 right-handed men who stuttered and 10 right-handed, age- and sex-matched non-stuttering controls. Ninety PET blood flow images were obtained in each cohort (nine per subject as three trials of each of three conditions) from which r-value statistical parametric images (SPI¿r¿) were computed. Brain correlates of stutter rate and syllable rate showed striking differences in both laterality and sign (i.e. positive or negative correlations). Stutter-rate correlates, both positive and negative, were strongly lateralized to the right cerebral and left cerebellar hemispheres. Syllable correlates in both cohorts were bilateral, with a bias towards the left cerebral and right cerebellar hemispheres, in keeping with the left-cerebral dominance for language and motor skills typical of right-handed subjects. For both stutters and syllables, the brain regions that were correlated positively were those of speech production: the mouth representation in the primary motor cortex; the supplementary motor area; the inferior lateral premotor cortex (Broca's area); the anterior insula; and the cerebellum. The principal difference between syllable-rate and stutter-rate positive correlates was hemispheric laterality. A notable exception to this rule was that cerebellar positive correlates for syllable rate were far more extensive in the stuttering cohort than in the control cohort, which suggests a specific role for the cerebellum in enabling fluent utterances in persons who stutter. Stutters were negatively correlated with right-cerebral regions (superior and middle temporal gyrus) associated with auditory perception and processing, regions which were positively correlated with syllables in both the stuttering and control cohorts. These findings support long-held theories that the brain correlates of stuttering are the speech-motor regions of the non-dominant (right) cerebral hemisphere, and extend this theory to include the non-dominant (left) cerebellar hemisphere. The present findings also indicate a specific role of the cerebellum in the fluent utterances of persons who stutter. Support is also offered for theories that implicate auditory processing problems in stuttering.


Electron dense artefactual deposits in tissue sections: the role of ethanol, uranyl acetate and phosphate buffer.
The occurrence of electron dense deposits in sections of aldehyde-fixed tissue prepared for transmission electron microscopy has been attributed to a number of conflicting factors. In an attempt to clarify this, the precipitating effect of different combinations of phosphate or cacodylate buffer, glutaraldehyde, ethanol and uranyl acetate was investigated in test tubes. As a preliminary investigation the combination of phosphate buffer, ethanol and uranyl acetate was investigated in heart and kidney tissue fixed in glutaraldehyde with or without postosmication. The essential factors in the formation of electron dense deposits in these tissues appear to be phosphate buffer, ethanol, and uranyl acetate, although glutaraldehyde may contribute in some way. The nature and intensity of the deposits seem to vary with the sequence of combination of these factors. Osmium did not appear to be an essential factor in the reaction since deposits were observed in both osmicated and unosmicated tissue. To avoid such deposits, a postosmication distilled water wash for 20 to 30 min followed by en bloc staining with aqueous uranyl acetate is advised if phosphate buffer is used as a fixative vehicle or buffer wash after the primary fixative.


Studying the oxidation of water to molecular oxygen in photosynthetic and artificial systems by time-resolved membrane-inlet mass spectrometry.
Monitoring isotopic compositions of gaseous products (e.g., H2, O2, and CO2) by time-resolved isotope-ratio membrane-inlet mass spectrometry (TR-IR-MIMS) is widely used for kinetic and functional analyses in photosynthesis research. In particular, in combination with isotopic labeling, TR-MIMS became an essential and powerful research tool for the study of the mechanism of photosynthetic water-oxidation to molecular oxygen catalyzed by the water-oxidizing complex of photosystem II. Moreover, recently, the TR-MIMS and (18)O-labeling approach was successfully applied for testing newly developed catalysts for artificial water-splitting and provided important insight about the mechanism and pathways of O2 formation. In this mini-review we summarize these results and provide a brief introduction into key aspects of the TR-MIMS technique and its perspectives for future studies of the enigmatic water-splitting chemistry.


Factors that influence mammography use and breast cancer detection among Mexican-American and African-American women.
This study examined factors that influence mammography use and breast cancer detection, including education, health insurance, and acculturation, among Mexican-American (MA) and African-American (AA) women. The study included 670 breast cancer cases (388 MAs and 282 AAs), aged 40-86 years at diagnosis. Data on mammography use, detection, and delay in seeking care were collected via questionnaires and medical records. Using a language-based bidimensional acculturation measure, MAs were classified as English-dominant (n = 67), bilingual (n = 173), and Spanish-dominant (n = 148). Mammography prior to diagnosis was assessed by racial/ethnic acculturation subgroup using logistic regression. In age-adjusted models, mammography use was non-significantly lower among English-dominant (OR = 0.84; 95% CI: 0.45-1.59) and bilingual (OR = 0.86; 95% CI: 0.55-1.35) MAs and significantly lower among Spanish-dominant MAs (OR = 0.53; 95% CI: 0.34-0.83) than among AA women. After adjustment for education or insurance, there was no difference in mammography use by race/ethnicity and acculturation subgroup. Despite high self-reported mammography use (75%), a large proportion of cases reported self-detection (59%) and delay in seeking care >90 days (17%). These findings favor promoting culturally appropriate messaging about the benefits and limitations of mammography, education about breast awareness, and prompt reporting of findings to a health professional.


Combined climate- and prey-mediated range expansion of Humboldt squid (Dosidicus gigas), a large marine predator in the California Current System.
Climate-driven range shifts are ongoing in pelagic marine environments, and ecosystems must respond to combined effects of altered species distributions and environmental drivers. Hypoxic oxygen minimum zones (OMZs) in midwater environments are shoaling globally; this can affect distributions of species both geographically and vertically along with predator-prey dynamics. Humboldt (jumbo) squid (Dosidicus gigas) are highly migratory predators adapted to hypoxic conditions that may be deleterious to their competitors and predators. Consequently, OMZ shoaling may preferentially facilitate foraging opportunities for Humboldt squid. With two separate modeling approaches using unique, long-term data based on in situ observations of predator, prey, and environmental variables, our analyses suggest that Humboldt squid are indirectly affected by OMZ shoaling through effects on a primary food source, myctophid fishes. Our results suggest that this indirect linkage between hypoxia and foraging is an important driver of the ongoing range expansion of Humboldt squid in the northeastern Pacific Ocean.


Clinical and electrocardiographic characteristics of infarctional ventricular ectopic beats: An observational study.
The purpose of this study was to explore the clinical and electrocardiographic characteristics of infarctional ventricular ectopic beats (IVEBs).Thirty-eight acute myocardial infarction (AMI) patients with IVEB and 109 AMI patients without IVEB were analyzed. The morphological changes of QRS complex, ST segment, and T wave were compared to IVEB with sinus rhythm from the same period and fully evolved phase.An IVEB QRS complex often revealed the right bundle branch block morphology, in addition to Q wave AMI; no-Q wave AMI also had IVEB. Single-factor analysis found that IVEB often appeared in early AMI (<6 hours), and they were more frequent in inferoposterior with/without right ventricular involvement, large area AMI and thrombolytic reperfusion than in anterior or anteroseptal myocardial infarction, small area AMI, and unthrombolytic nonreperfusion. Multifactors no conditional logistic regression analysis revealed a positive correlation between IVEB and early AMI, AMI size, Killip heart function degree, inferoposterior with/without right ventricular involvement, and thrombolytic reperfusion. The Q wave of IVEB was wider, and the ST segment elevation was higher than those of the same period in sinus rhythms. The infarctional morphological changes of IVEB could be found before the same period in sinus rhythm and elevated myocardial enzymes.IVEBs were not rare. They were useful for early diagnosis and location of AMI.


Integrative approach identifies SLC6A20 and CXCR6 as putative causal genes for the COVID-19 GWAS signal in the 3p21.31 locus.
To date, the locus with the most robust human genetic association to COVID-19 severity is 3p21.31. Here, we integrate genome-scale CRISPR loss-of-function screens and eQTLs in diverse cell types and tissues to pinpoint genes underlying COVID-19 risk. Our findings identify SLC6A20 and CXCR6 as putative causal genes that modulate COVID-19 risk and highlight the usefulness of this integrative approach to bridge the divide between correlational and causal studies of human biology.


A study of induction of nerve regeneration using bioabsorbable tubes.
A silicone tube (S-tube) was packed with CPLA (copolymer of poly-L-lactide) fibers (S-tube+CPLA) or collagen fibers (S-tube+fiber). Two types of tube were prepared from a collagen sheet (Col-tube) and a bioabsorbable atelocollagen membrane for guided tissue regeneration (GTR-tube). They were packed with collagen fibers or films (Col-tube+fiber, GTR-tube+fiber and GTR-tube+film). Bridge grafting (15 mm in length) was performed with these tubes in a rat sciatic nerve model. Specimens were harvested after 8 weeks. Minifascicles were formed in the open space between the CPLA fibers in the S-tube+CPLA group. Regenerated axons were also formed in the degenerated collagen fibers in the S-tube+Col group. Immunocytochemistry evaluation revealed that Schwann cells invaded the space in the absorbing collagen fibers. Histologic analysis of the regenerated axons in the groups with Col-tubes or GTR-tubes revealed that both the Col-tube and the GTR-tube packed with collagen fibers were effective in providing a scaffold for regenerating nerve tissue.


An Online Survey of the Perceptions of Clinical and Non-Clinical Professionals on Healthcare for Non-Communicable Diseases and COVID-19 Measures During the Pandemic in Malaysia.
Objectives: This study assesses the opinions of health professionals in Malaysia on the disruption of non-communicable disease (NCD) services during the COVID-19 pandemic from March 2020 to January 2022. Methods: We conducted a cross-sectional online survey with 191 non-clinical public health workers and clinical health service workers in Malaysia from November 2021 to January 2022. Participants were recruited by the Malaysian Ministry of Health using major networks including key experts and practitioners. Secondary respondents were subsequently enrolled through snowballing. Results: The most notable issues raised by the survey participants relate to NCD service disruption, the redirection of NCD care resources, and NCD care being overburdened post-pandemic. Respondents also reported accounts of resilience and prompt reaction from the healthcare system, as well as calls for innovation. Conclusion: Most respondents perceived that the challenges arising from COVID-19 were mostly managed well by the healthcare system, which was able to provide the necessary services to NCD patients during this health emergency. However, the study identifies gaps in the health system response and preparedness capacity, and highlights solutions for strengthening NCD services.


Bertolotti Syndrome With Articulated L5 Transverse Process Causing Intractable Back Pain: Surgical Video Showcasing a Minimally Invasive Approach for Disconnection: 2-Dimensional Operative Video.
Bertolotti syndrome is a commonly missed cause of intractable back pain that affects 4% to 8% of the general population. It involves the congenital malformation of a transitional lumbosacral vertebra, with total or partial and unilateral or bilateral transverse process (TP) fusion or articulation to the sacrum. The pain can be debilitating, and the tethering of the spine to the sacrum can encourage deformity formation in the coronal plane and lead to early degenerative changes, especially if present only unilaterally. We present the case of a 24-yr-old woman with no notable prior medical history who presented with years of lower axial back pain radiating to her thighs, which limited her activities of daily living and was resistant to conservative management. Her imaging showed an abnormally large left L5 TP, which was articulated to the sacrum, and signs of early coronal deformity. She had responded almost completely to repeated steroid injections into the TP-sacral joint, but that effect was very transient. Informed patient consent was obtained prior to her surgery. She underwent a minimally invasive tube disconnection of the abnormal joint with partial distal resection of the TP, and her symptoms completely resolved. This case highlights the importance of correlating clinical symptoms with aberrant anatomy, and the role of selective surgery in providing symptomatic relief. This case report was written in compliance with our institutional ethical review board approval, and patient consent was waived in light of the retrospective and deidentified nature of the data presented in accordance with the University of Texas Southwestern institutional review board.


An Intervention to Promote Medication Understanding and Use Self-Efficacy: Design of Video Narratives for Aging Patients at Risk of Recurrent Stroke.
The debilitating effects of recurrent stroke among aging patients have urged researchers to explore medication adherence among these patients. Video narratives built upon Health Belief Model (HBM) constructs have displayed potential impact on medication adherence, adding an advantage to patient education efforts. However, its effect on medication understanding and use self-efficacy have not been tested. The researchers believed that culturally sensitive video narratives, which catered to a specific niche, would reveal a personalized impact on medication adherence. Therefore, this study aimed to develop and validate video narratives for this purpose. This study adapted the Delphi method to develop a consensus on the video scripts' contents based on learning outcomes and HBM constructs. The panel of experts comprised 8 members representing professional stroke disease experts and experienced poststroke patients in Malaysia. The Delphi method involved 3 rounds of discussions. Once the consensus among members was achieved, the researchers drafted the initial scripts in English, which were then back translated to the Malay language. A total of 10 bilingual patients, within the study's inclusion criteria, screened the scripts for comprehension. Subsequently, a neurologist and poststroke patient narrated the scripts in both languages as they were filmed, to add to the realism of the narratives. Then, the video narratives underwent a few cycles of editing after some feedback on video engagement by the bilingual patients. Few statistical analyses were applied to confirm the validity and reliability of the video narratives. Initially, the researchers proposed 8 learning outcomes and 9 questions based on HBM constructs for the video scripts' content. However, following Delphi rounds 1 to 3, a few statements were omitted and rephrased. The Kendall coefficient of concordance, W, was about 0.7 (P<.001) for both learning outcomes and questions which indicated good agreement between members. Each statement's Cronbach alpha was above .8 with SD values within a range below 1.5 that confirmed satisfactory content and construct validity. Approximately 75% (6/8) of members agreed that all chosen statements were relevant and suitable for video script content development. Similarly, more than 80% (8/10) of patients scored video engagement above average, intraclass correlation coefficient was above 0.7, whereas its Kendall W was about 0.7 with significance (P<.001), which indicated average agreement that the video narratives perceived realism. The Delphi method was proven to be helpful in conducting discussions systematically and providing precise content for the development of video narratives, whereas the Video Engagement Scale was an appropriate measurement of video realism and emotions, which the researchers believed could positively impact medication understanding and use self-efficacy among patients with stroke. A feasibility and acceptability study in an actual stroke care center is needed. Australian New Zealand Clinical Trials Registry ACTRN12618000174280; https://www.anzctr.org.au /Trial/Registration/TrialReview.aspx?id=373554&isReview=true.


The Association between Perceived Adequacy and Capacity for School Food Policy Implementation with Food Availability and Policy Adherence in Nova Scotia, Canada.
Supporting the implementation of school food and nutrition policies is an international priority to encourage healthier eating among children and youth. Schools are an important intervention setting to promote childhood nutrition, and many jurisdictions have adopted policies, guidelines, and programs to modify the school nutrition environment and promote healthier eating. The purpose of this study was to explore the association between perceived adequacy of facilities or equipment and capacity of staff to support policy implementation with food availability and policy adherence in the province of Nova Scotia (NS), Canada, one of the first regions in Canada to launch a comprehensive school food and nutrition policy (SFNP). A cross-sectional online survey was conducted in 2014-2015 to provide a current-state assessment of policy implementation and adherence. Adequacy and capacity for food policy implementation was used to assess policy adherence through the availability of prohibited 'minimum' nutrition foods. An exploratory factor analysis was conducted on a selection of available foods, and 'slow'- and 'quick'-service food composition measures were dichotomized for food availability. Schools with above-average perceived adequacy and capacity for policy implementation had greater odds (OR = 3.62, CI = 1.56, 8.40) of adhering to a lunch policy, while schools that adhered to a snack and lunch policy had lower odds (OR = 0.48, CI = 0.23, 1.01 and OR = 0.18, CI = 0.08, 0.41) of serving quick-service foods. This study identified the need for appropriate adequacy of facilities or equipment and capacity of staff for policy implementation to ensure policy adherence and improve the school food environment. These findings highlight the relationship between school food and nutrition policies, suggesting that better supporting their implementation could increase the likelihood of their success.


Bone and mineral disorders in chronic kidney disease: implications for cardiovascular health and ageing in the general population.
The patient with chronic kidney disease (CKD) represents an extreme model for arteriosclerosis, vascular calcification, and bone disorders, all of which are also associated with ageing in the general population. These pathological features are also relevant to other common chronic health disorders such as diabetes, and chronic inflammatory and cardiovascular diseases. Although management and interventions for these major risk factors are now incorporated into most public health guidelines (eg, smoking cessation and control of bodyweight and blood pressure, as well as glucose and cholesterol concentrations), some residual cardiovascular risk is not reduced by implementation of these interventions. CKD should be regarded as an atypical disease in which both traditional and novel cardiovascular risk factors have effects on outcomes. But CKD can also be viewed conceptually as an accelerator of traditional cardiovascular risk factors. Findings from research into mineral bone disorder associated with CKD (CKD-MBD) could help the medical community to better understand the vascular actions of certain molecules, such as phosphates, fibroblast growth factor 23, parathyroid hormone, sclerostin, or vitamin D and their relevance to the management of different pathologies in the general population. Importantly, these components, which are recognised in nephrology, could help to explain residual risk of cardiovascular events in the general population. Thus, achieving a better understanding of CKD-MBDs could provide substantial insight into future treatments for arteriosclerosis and osteoporosis, which are strongly associated with ageing and morbidity in the general population.


Nucleolin is required for efficient nuclear egress of herpes simplex virus type 1 nucleocapsids.
Herpesvirus nucleocapsids assemble in the nucleus and must cross the nuclear membrane for final assembly and maturation to form infectious progeny virions in the cytoplasm. It has been proposed that nucleocapsids enter the perinuclear space by budding through the inner nuclear membrane, and these enveloped nucleocapsids then fuse with the outer nuclear membrane to enter the cytoplasm. Little is known about the mechanism(s) for nuclear egress of herpesvirus nucleocapsids and, in particular, which, if any, cellular proteins are involved in the nuclear egress pathway. UL12 is an alkaline nuclease encoded by herpes simplex virus type 1 (HSV-1) and has been suggested to be involved in viral DNA maturation and nuclear egress of nucleocapsids. Using a live-cell imaging system to study cells infected by a recombinant HSV-1 expressing UL12 fused to a fluorescent protein, we observed the previously unreported nucleolar localization of UL12 in live infected cells and, using coimmunoprecipitation analyses, showed that UL12 formed a complex with nucleolin, a nucleolus marker, in infected cells. Knockdown of nucleolin in HSV-1-infected cells reduced capsid accumulation, as well as the amount of viral DNA resistant to staphylococcal nuclease in the cytoplasm, which represented encapsidated viral DNA, but had little effect on these viral components in the nucleus. These results indicated that nucleolin is a cellular factor required for efficient nuclear egress of HSV-1 nucleocapsids in infected cells.


Structural changes in the model of the outer cell membrane of Gram-negative bacteria interacting with melittin: an in situ spectroelectrochemical study.
The cell membrane of Gram-negative bacteria interacting with an antimicrobial peptide presents a complex supramolecular assembly. Fabrication of models of bacterial cell membranes remains a large experimental challenge. Langmuir-Blodgett and Langmuir-Schaefer (LS-LB) transfer makes possible the deposition of multicomponent asymmetric lipid bilayers onto a gold surface. Two lipids: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) and di[3-deoxy-D-manno-octulosonyl]-lipid A (KLA) were used to deposit a model of the outer membrane of Gram-negative bacteria on the Au(111) substrate. The use of gold as the solid substrate enables control of the membrane potential. Molecular scale changes in the model membrane exposed to physiological electric fields and interacting with melittin antimicrobial peptide are discussed in this paper. The interaction of the outer membrane with melittin leads to an increase in the membrane capacitance and permeability to ions and water. The stability of the outer membrane with bound melittin decreases at positive membrane potentials. In situ polarization modulation infrared reflection absorption spectroscopy is used to investigate membrane potential-dependent changes in the structure of the outer membrane interacting with melittin. The hydration of the ester carbonyl groups is not affected by the interaction with melittin. However, the orientation and hydrogen bond network with the carboxylate groups in KLA changes drastically after POPE-KLA bilayer interacts with melittin. We propose that the positively charged groups in the amino acids present at the C-terminus of the peptide interact directly with the polar head group of KLA. Simultaneously, the packing order in hydrocarbon chains in the membrane with bound melittin increases. A hydrophobic match between the chains in the lipids and the peptide, which spans the membrane, seems to be responsible for the ordering of the hydrocarbon chains region of the bilayer. The N-terminus enters into the hydrophobic region of the membrane and forms a channel to the hydrophilic head groups in POPE.


Effects of surgery type and attention focus on children's coping.
How children cope with minor or major surgery is influenced by their attention focus appraisals. Although factors that predict children's coping with surgery have been identified (i.e., age, locus of control, parent-doctor information, worry), it still is not known whether the type of surgery per se affects the coping strategies used and influences previously established predictors of coping. Furthermore, questions remain concerning the relation among type of surgery, attention focus, and coping. The purpose of this study was to determine whether the type of surgery (minor vs. major) would have a differential effect on coping, and whether coping can be predicted better if it is known what type of attention focus (appraisal) the child has. Data from three studies of children (n = 189) undergoing minor or major surgery were combined to examine the effects that type of surgery and attention have on coping. Measures included the Preoperative Mode of Coping Interview, Locus of Control Scale for Children, Parent-Doctor Information Interview, and a measure for worry. The results showed that the factors previously found to predict coping were upheld in the combined sample and accounted for 50% of the variance in coping. Type of surgery was significantly associated with coping: Children undergoing minor surgery were somewhat more vigilant than children undergoing major surgery. The inclusion of attention in the analysis significantly improved the variance explained in coping (66%), and children who had a concrete-objective focus of attention were found to be more vigilant. Significant interactions were found between attention focus and type of surgery, locus of control, and age. Type of surgery also had a significant interaction with worry. Children who focused on the concrete-objective aspects of the situation were more vigilant if they were having minor rather than major surgery. Also, children who had an internal locus of control and a concrete-objective focus of attention were more vigilant in coping. Regardless of age, children who had a concrete-objective focus of attention were more vigilant. Furthermore, at low levels of worry, children undergoing major surgery were more vigilant than children undergoing minor surgery. Coping with surgery is influenced by multiple factors. Children's ability to focus attention on the concrete-objective aspects of surgery may help to reduce feelings of threat that could impede their use of vigilant coping.


Methylsulfonylmethane Induces G1 Arrest and Mitochondrial Apoptosis in YD-38 Gingival Cancer Cells.
Gingival squamous cell carcinoma is a rare form of cancer that accounts for less than 10% of all head and neck cancers. Targeted therapies with natural compounds are of interest because they possess high efficacy with fewer side-effects. Methylsulfonylmethane (MSM) is an organic sulfur-containing compound with anticancer activities. The main goal of this study was to induce proliferation inhibition and apoptosis in the metastatic YD-38 cell line. MSM up-regulated expression of P21Waf1/Cip1 and P27Kip1 genes and down-regulated expression of cyclin D1 (CCND1) and CDK4. Moreover, treatment with MSM induced apoptosis and up-regulation of BAX in YD-38 cells. In accordance, the expression of the BCL-2 and BCL-XL, were inhibited, indicating the role of mitochondria in MSM-induced apoptosis. Analysis of mitochondrial integrity showed a loss of mitochondrial potential with an increased level of cytochrome c in the cytosol compared to mitochondria. Active CASPASE-3 (CASP3) was also observed, confirming that MSM-induced apoptosis is caspase-mediated.


Fetal femur length and gestational age.
Ultrasound measurement of the fetal femur length during the second trimester is now possible and is a good indicator of fetal age, comparing favorably with measurement of fetal biparietal diameter. It is a simple technique and can be performed quickly. The prospect of the first fetal physical examination is fast becoming a reality, and this technique adds a new dimension.


Test characteristics of immunofluorescence and ELISA tests in 856 consecutive patients with possible ANCA-associated conditions.
To examine the test characteristics of immunofluorescence (IF) and enzyme-linked immunosorbent assays (ELISA) in a consecutive series of patients under evaluation for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Using stored sera, we performed a cross-sectional study on 856 consecutive patients tested prospectively for ANCA by IF, Based on guidelines from the 1994 Chapel Hill Consensus Conference (CHCC), we determined each patient's underlying diagnosis by a medical records review without regard to their ANCA status (the CHCC guidelines do not require ANCA as a prerequisite for diagnosis). We grouped patients with forms of vasculitis commonly associated with ANCA into one of 4 types of AAV: Wegener's granulomatosis (n = 45), microscopic polyangiitis (n = 12), Churg-Strauss syndrome (n = 4), and pauci-immune glomerulonephritis (n = 8). We also classified patients without clinical evidence of AAV (92% of all patients tested) into 5 predefined categories of disease (including "other") and an additional category for no identifiable disease. In a blinded fashion, we then performed ELISAs on the stored serum for antibodies to proteinase-3 (PR3) and myeloperoxidase (MPO) and calculated the test characteristics for both ANCA assay techniques. Sixty-nine of the 856 patients (8.1%) had clinical diagnoses of AAV based on CHCC guidelines. The positive predictive value (PPV) of ELISA for AAV was superior to that of IF, 83% versus 45%. For patients with both positive IF tests and positive ELISA tests, the PPV increased to 88%. Both IF and ELISA had high negative predictive values (97% and 96%, respectively). Positive ELISA tests were associated with higher likelihood ratios (LR) than IF (54.2 [95% CI = 26.3, 111.5] versus 9.4 [95% CI = 6.9, 12.7]). The LR of both a positive IF and a positive ELISA was 82.1 (95% CI = 33.3, 202.5). Compared with IF, an ELISA test fo ANCA was associated with a substantially higher PPV and LR for AAV. This fact, combined with the greater sensitivity of IF, suggests that an effective testing strategy is to perform ELISA tests only on samples that are positive for ANCA by IF.


Frontal sinus abscess and secondary orbital cellulitis.
Despite modern antibiotics, frontal sinus abscess (and secondary orbital cellulitis) remains relatively common and potentially life-threatening. The declining incidence of chronic middle ear disease in the UK has made it one of the commonest causes of intracranial abscess. The speed with which suppuration can penetrate the sinus walls remains poorly understood and a research challenge. Management is best supervised by an ENT surgeon because the key decision is the timing of sinus surgery. The ENT surgeon, nevertheless, must be alert to the indications for consultation with neurosurgical colleagues. This paper aims to give an illustrated account of the clinico-pathological features and current management.


ISPD 2021 debate - All in vitro fertilization cycles should involve pre-implantation genetic testing to improve fetal health and pregnancy outcomes.
For 3 decades, couples at increased risk for a genetic disorder have been offered preimplantation genetic testing (PGT). Simultaneously, PGT for aneuploidy (PGT-A) to improve in vitro fertilization (IVF) outcomes was introduced, but evidence of value-added remains inconsistent. Recently, lower genetic testing costs and shorter turnaround time have reinvigorated PGT-A. Additionally, a shift from blastomere (day 3) to blastocyst (day 5) transfer and embryo freezing advances support PGT without the time constraints of immediate transfer. PGT-A transformed from a time-constrained analysis of 1-2 cells to an "add on" study for all IVF. But should it be offered to all IVF patients? And if not, under what conditions? Pre-debate polling found 64% opposed to PGT for all IVF cycles with concerns voiced about cost, informed consent, and a "slippery slope". Leaving aside the inconsistent evidence of IVF improvement whether measured as miscarriage or livebirths with PGT-A, the debaters grappled with patient and provider desires versus the ethical concerns for the unborn child. However, the audience was not swayed; two thirds remained opposed to PGT for all IVF cycles.


Elementary sensory deficits in schizophrenia indexed by impaired visual mismatch negativity.
Mismatch negativity (MMN) is an automatic brain response to unexpected events. It represents a prediction error (PE) response, reflecting the difference between the sensory input and predictions. While deficits in auditory MMN are well known in schizophrenia, only few studies investigated impairments in predictive visual processing in schizophrenia. These studies used complex stimuli such as motion direction and emotional facial expressions. Here we studied whether automatic predictive processing of elementary features such as orientation is also impaired in schizophrenia. Altogether 28 patients with schizophrenia and 27 healthy controls matched in age, gender, and education participated in the study. EEG was recorded using 128 channels in the two experimental blocks. Using an oddball paradigm, horizontal stripes of Gabor patches were presented as frequent standards and vertical stripes as rare deviants in one block. Stimulus probabilities were swapped in the other block. Mismatch responses were obtained by subtracting responses to standard from those to deviant stimuli. We found significant mismatch responses in healthy controls but not in patients in the prefrontal and occipital-parietal regions in the 90-200ms interval. Furthermore patients showed significantly decreased deviant minus standard difference waveforms relative to controls in the same regions with moderate to large effect sizes. Our findings demonstrate that predictive processing of unattended low-level visual features such as orientation is impaired in schizophrenia. Our results complement reports of sensory deficits found in tasks requiring attentive processing and suggest that deficits are present in automatic visual sensory processes putatively mediated by glutamatergic functioning.


Current and future modalities of catheter ablation for the treatment of cardiac arrhythmias.
Catheter ablation has proven to be a safe and effective treatment for a wide variety of cardiac arrhythmias. By destroying the critical zone of conductive tissue responsible for impulse generation or propagation, the arrhythmias may be cured. A variety of modalities of catheter ablation have been tested in the past decade. Initially, high energy direct current shocks delivered through a conventional electrode catheter were used. Now, use of radiofrequency energy as a power supply has resulted in higher efficacy and much improved safety of this technique. New approaches including low energy direct current shock ablation, microwave hyperthermic ablation, and laser photocoagulation are being tested, and may result in further refinement of nonsurgical curative therapy of arrhythmias.


Extraction site healing complicated by neoplasia.
Malignant melanoma arises from melanocytes, dendritic cells of neural crest origin. Melanocytes occur within the basal layers of the epidermis, mucous membranes, retina and uveal structures of the eye and the meninges. Rarely, they may also occur in the bladder, adrenal medulla and ovaries. These melanomas metastasise widely and metastases in the oral mucosa have been seen in about 3% of patients with cutaneous melanoma, and can complicate the healing of extraction sites. This paper presents a case of malignant melanoma of the mandible.


The Influence of Cone Age and Urbanisation on the Diversity and Community Composition of Culturable Seed Fungal Endophytes within Native Australian Banksia ericifolia L.f. subsp. ericifolia.
Seed fungal endophytes play a crucial role in assisting the overall health and success of their host plant; however, little is known about the factors that influence the diversity and composition of these endophytes, particularly with respect to how they change over time and within urban environments. Using culturing techniques, morphological analyses, and Sanger sequencing, we identified the culturable seed fungal endophytes of Banksia ericifolia at two urban and two natural sites in Sydney, New South Wales, Australia. A total of 27 Operational Taxonomic Units were obtained from 1200 seeds. Older cones were found to contain, on average, more colonised endophytes than younger cones. Species richness was also significantly influenced by cone age, with older cones being more speciose. Between urban and natural sites, the overall community composition did not change, although species richness and diversity were greatest at urban sites. Understanding how these endophytes vary in time and space may help provide an insight into the transmission pathways used and the potential role they play within the development and survival of the seed. This knowledge may also be crucial for restoration purposes, especially regarding the need to consider endophyte viability in ex situ seed collection and storage in seed-banking practices.


Noninvasive imaging analysis of biological tissue associated with laser thermal injury.
The purpose of our study is to use a noninvasive tomographic imaging technique with high spatial resolution to characterize and monitor biological tissue responses associated with laser thermal injury. Optical doppler tomography (ODT) combines laser doppler flowmetry (LDF) with optical coherence tomography (OCT) to obtain high resolution tomographic velocity and structural images of static and moving constituents in highly scattering biological tissues. A SurgiLase XJ150 carbon dioxide (CO2) laser using a continuous mode of 3 watts (W) was used to create first, second or third degree burns on anesthetized Sprague-Dawley rats. Additional parameters for laser thermal injury were assessed as well. The rationale for using ODT in the evaluation of laser thermal injury offers a means of constructing a high resolution tomographic image of the structure and perfusion of laser damaged skin. In the velocity images, the blood flow is coded at 1300 μm/s and 0 velocity, 1000 μm/s and 0 velocity, 700 μm/s and 0 velocity adjacent to the first, second, and third degree injuries, respectively. ODT produces exceptional spatial resolution while having a non-invasive way of measurement, therefore, ODT is an accurate measuring method for high-resolution fluid flow velocity and structural images for biological tissue with laser thermal injury.


Morphological, Molecular, and Biochemical Characterization of Monounsaturated Fatty Acids-Rich Chlamydomonas sp. KIOST-1 Isolated from Korea.
Microalgae hold promise as producers of sustainable biomass for the production of biofuels and other biomaterials. However, the selection of strains with efficient and robust production of desirable resources remains challenging. In this study, we isolated a green microalga from Korea and analyzed its morphological, molecular, and biochemical characteristics. Microscopic and phylogenetic analyses demonstrated that the isolate could be classified into the genus Chlamydomonas, and we designated the isolate Chlamydomonas s p. K IOST -1. Compositions of protein, lipid, and carbohydrate in the microalgal cells were estimated to be 58.8 ± 0.2%, 22.7 ± 1.2%, and 18.5 ± 1.0%, respectively. Similar to other microalgae belonging to Chlorophyceae, the dominant amino acid and monosaccharide in Chlamydomonas sp. KIOST-1 were glutamic acid and glucose. On the other hand, the proportions of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids clearly differed from other species in the genus Chlamydomonas, and monounsaturated fatty acids accounted for a large portion (41.3%) of the total fatty acids in the isolate. Based on these results, Chlamydomonas sp. KIOST-1 has advantageous characteristics for biomass production.


Azathioprine therapy for patients with systemic lupus erythematosus.
Azathioprine is the only purine analog that is widely used for the management of systemic lupus erythematosus (SLE). For SLE patients without renal involvement, it is given to those patients who require a maintenance dose of 15 mg or higher of prednisone and for those who experience recurrent flares. Azathioprine in combination with steroids may be given to a large number of patients with lupus nephritis. It is also effective for patients with skin lesions, pneumonitis, thrombocytopenia or hemolytic anemia. Azathioprine may be used during pregnancy but not during lactation. It has not been shown to increase the risk for the development of malignancies among patients with SLE.


[Cystine lithiasis in the adult. Apropos of an isolated case without familial antecedents].
We report on a case of cystinuria in an adult woman without any familial or self stone-forming history. The first symptom appeared at 43 years, as an acute renal colic caused by an obstructing ureteral calculous. Hence, this case differs from the majority in its isolated form of presentation and its uncommon age of incidence. Two clinic aspects of cystinuria are emphasized: the precocity of recurrence or stone growth without treatment, and the success obtained frequently in relapses prevention with prophylactic measures (dietary patterns, urine alkalinisation), and continued medical therapy.