Esmolol pretreatment reduces the frequency and severity of pain on injection of rocuronium.
To determine the effect of esmolol on the frequency and severity of pain and withdrawal reactions after injection of rocuronium and to compare it with lidocaine and placebo. Prospective, randomized, double-blind, placebo-controlled study. Single university hospital. 120 ASA physical status I and II patients undergoing general anesthesia for elective surgery. Patients were randomized to receive esmolol (0.5 mg/kg), lidocaine (0.5 mg/kg), or placebo, followed by a subparalyzing dose of rocuronium. After induction of anesthesia with propofol and fentanyl, an intubating dose of rocuronium 0.6 mg/kg was given. Patients were observed after injection of rocuronium 0.05 mg/kg, then immediately asked if they had pain in the arm. The response was assessed; discomfort, pain, and withdrawal of the hand were recorded and graded using a 4-point scale (none, mild, moderate, or severe). After the intubating dose of rocuronium, withdrawal reactions were scored as follows: (a) no pain response, (b) pain limited to the wrist, (c) pain limited to the elbow/shoulder, or (d) generalized pain response. 31 patients (77.5%) in the esmolol group, 32 (80%) in the lidocaine group, and 15 (37.5%) in the placebo group reported no pain (both groups vs placebo, P < 0.001). Moderate pain was seen in only one patient receiving lidocaine, in 6 placebo patients, but in none in the esmolol group (esmolol vs placebo, P < 0.05). Severe pain was felt by 8 patients receiving placebo, but by none receiving esmolol or lidocaine (P < 0.01). Frequency of withdrawal response after rocuronium was 2.5%, 17.5%, and 40% in the esmolol, lidocaine, and placebo groups, respectively (esmolol group vs placebo, P < 0.001; lidocaine group vs placebo, P < 0.05). Esmolol, like lidocaine, reduces the frequency of pain and withdrawal reaction associated with rocuronium injection.


Allosteric regulation of lysosomal enzyme recognition by the cation-independent mannose 6-phosphate receptor.
The cation-independent mannose 6-phosphate receptor (CI-MPR, IGF2 receptor or CD222), is a multifunctional glycoprotein required for normal development. Through the receptor's ability to bind unrelated extracellular and intracellular ligands, it participates in numerous functions including protein trafficking, lysosomal biogenesis, and regulation of cell growth. Clinically, endogenous CI-MPR delivers infused recombinant enzymes to lysosomes in the treatment of lysosomal storage diseases. Although four of the 15 domains comprising CI-MPR's extracellular region bind phosphorylated glycans on lysosomal enzymes, knowledge of how CI-MPR interacts with ~60 different lysosomal enzymes is limited. Here, we show by electron microscopy and hydroxyl radical protein footprinting that the N-terminal region of CI-MPR undergoes dynamic conformational changes as a consequence of ligand binding and different pH conditions. These data, coupled with X-ray crystallography, surface plasmon resonance and molecular modeling, allow us to propose a model explaining how high-affinity carbohydrate binding is achieved through allosteric domain cooperativity.


[Leishmaniasis in Navarra, Spain (1976-2018): an update].
Leishmaniasis is endemic in countries of the Mediterranean area. In this study, the information available on leishmaniasis in Navarra in the period 1976-2018 and in the bordering regions was collected, along with an overview of the situation of this disease at the national level, from the vector to humans. Aragón exhibited a lower incidence rate in the last ten years (2008-2018) compared to the previous decade, while Navarra and La Rioja have almost doubled the number of cases per 100,000 inhabitants and, likewise, incidence in the Basque Country has also increased. At the national level, since 2015, such an increase has become significant due to the inclusion of human leishmaniasis as a mandatory notifiable disease. Currently in Spain, although the incidence of human leishmaniasis is not a situation of high concern, it is however a reality. Therefore, it is necessary to monitor its evolution.


Electron capture gas chromatography detection and mass spectrum identification of 3-(2'-ketohexyl)indoline in spinal fluids of patients with tuberculous meningitis.
A basic, extractable, indolic type of compound, which was derivatized with heptafluorobutyric anhydride and pyridine, was obtained from the cerebrospinal fluids of patients with acute tuberculous meningitis. The compound was detected by frequency-pulsed, modulated electron capture gas-liquid chromatography, and it was tentatively identified by mass spectrometry as 3-(2'-ketohexyl)indoline. The compound was found to be valuable for differentiating between tuberculous, cryptococcal, and aseptic meningitides.


Successful excision of a giant subcarinal bronchogenic cyst by video-assisted thoracoscopic surgery.
Mediastinal bronchogenic cysts, regarded as congenital foregut abnormalities, are uncommon. These cysts can compress adjacent structures, causing obstructive symptoms and complications. A 57-year-old man was admitted to our hospital with complaints of tachycardia, dyspnea, and chest pain. Enhanced computed tomography revealed a 90 × 90 mm, well-defined subcarinal cystic mass causing significant compression and stenosis of the right main bronchus, right pulmonary artery, and right inferior pulmonary vein. The mass was successfully excised using one window and two-port video-assisted thoracoscopic surgery with partial resection and repair of pulmonary artery, and the postoperative course was good with no recurrence.


Chemical modification of enzymes with activated magnetic modifier.
An activated magnetic modifier, which could render biological materials magnetic property, was synthesized in following two steps: oxidation of ferrous ions (Fe2+) with hydrogen peroxide in the presence of alpha, omega-dicarboxymethylpoly(oxyethylene) (DCPEG) to obtain DCPEG-magnetite (Fe3O4); free carboxyl groups in the DCPEG-magnetite were activated with N-hydroxysuccinimide. By coupling the activated magnetic modifier to amino groups of lipase or L-asparaginase, magnetic enzymes were prepared. They dispersed stably not only in aqueous solution but also in organic solvents with high enzymic activities. Magnetic enzymes were readily recovered from reaction mixture in a magnetic field of 6000 Oe without loss of enzymic activity.


Sporotrichoid leishmaniasis in patients from Saudi Arabia: clinical and histologic features.
The clinical and pathologic presentations of cutaneous leishmaniasis in the various countries of the Middle East are well documented. The defined patterns currently encountered in the region emphasize the rarity of local extension of the infection from the bite site. Between 1970 and 1980 we have seen 24 patients with cutaneous leishmaniasis who acquired the infection in Saudi Arabia. In these patients there were several interesting variations from the hitherto described patterns of Oriental sore. The variations include, clinically, the appearance of satellite lesions and the presence of sporotrichoid spread of infection; and histologically, the presence of stellate intradermal abscesses. Such variations in the clinical and pathologic presentations may be due to differences either in the host's immunologic reactivity or in the Leishmania organisms found in Saudi Arabia. Speculative evidence supports the possibility of a different strain and/or species of Leishmania tropica in Saudi Arabia, which in turn may be responsible for this unique clinicopathologic presentation.


Neural coding for the retrieval of multiple memory patterns.
We investigate the retrieval dynamics in a feature-based semantic memory model, in which the features are coded by neurons of the Hindmarsh-Rose type in the chaotic regime. We consider the retrieval process as consisting of the synchronized firing activity of the neurons coding for the same memory pattern. The retrieval dynamics is investigated for multiple patterns, with particular attention to the case of overlapping memories. In this case, we hypothesize a dynamical nontransitive mechanism based on synchronization, that allows for a shared feature to participate in multiple memory representations. The problem of the choice of a cognitive plausible time-scale for the retrieval analysis is investigated by analyzing the information that can be inferred from finite-time analyses. Different types of indicators are proposed in order to evaluate the temporal dynamics of the neurons engaged in the retrieval process. We interpret the simulation results as suggestive of a role for chaotic dynamics in allowing for flexible composition of elementary meaningful units in memory representations.


A 35-year-old father with persistent Mullerian duct syndrome and seminoma of the right undescended testis: a rare case report.
A persistent Müllerian duct syndrome is a rare disorder of sexual differentiation characterized by the presence of the female reproductive system in a normal male. Herein, we report a case of a 35-year-old father with persistent Müllerian duct syndrome and seminoma in the right undescended testis. The exploratory laparotomy was performed and revealed a mass in the right undescended testis and Müllerian duct structures. For patients with cryptorchidism and inguinal hernia, the persistent Müllerian duct syndrome should be considered, and radiological evaluation of the genitourinary system is recommended for early diagnosis of persistent Müllerian duct syndrome. The persistent Müllerian duct syndrome is usually detected during a surgical operation, and it is considered a risk factor for developing testicular malignancies.


GABA and behavior: the role of receptor subtypes.
The discovery of different GABA receptor subtypes has stimulated research relating this neurotransmitter to a variety of behavioral functions and clinical disorders. The development of new and specific GABAergic compounds has made it possible to try to identify the specific functions of these receptors. The purpose of the present review is to evaluate the data regarding the functions of the GABA receptor subtypes in different behaviors such as motor function, reproduction, learning and memory, and aggressive-defensive behaviors. A description of GABAergic functions (stress, peripheral effects, thermoregulation) that might directly or indirectly affect behavior is also included. The possible involvement of GABA in different neurological and psychiatric disorders is also discussed. Although much research has been done trying to identify the possible role of GABA in different behaviors, the role of receptor subtypes has only recently attracted attention, and only preliminary data are available at present. It is therefore evident that still much work has to be done before a clear picture of the behavioral significance of these receptor subtypes can be obtained. Nevertheless, existing data are sufficient to justify the prediction that GABAergic agents, in the near future, will be much used in the field of behavioral pharmacology. It is hoped that the present review will contribute to this. Some specific suggestions concerning the most efficient way to pursue future research are also made.


PGC-1-related coactivator (PRC) negatively regulates endothelial adhesion of monocytes via inhibition of NF κB activity.
PGC-1-related coactivator (PRC) is a growth-regulated transcriptional cofactor known to activate many of the nuclear genes specifying mitochondrial respiratory function. Endothelial dysfunction is a prominent feature found in many inflammatory diseases. Adhesion molecules, such as VCAM-1, mediate the attachment of monocytes to endothelial cells, thereby playing an important role in endothelial inflammation. The effects of PRC in regards to endothelial inflammation remain unknown. In this study, our findings show that PRC can be inhibited by the inflammatory cytokine LPS in cultured human umbilical vein endothelial cells (HUVECs). In the presence of LPS, the expression of endothelial cell adhesion molecular, such as VCAM1 and E-selectin, is found to be increased. These effects can be negated by overexpression of PRC. Importantly, monocyte adhesion to endothelial cells caused by LPS is significantly attenuated by PRC. In addition, overexpression of PRC protects mitochondrial metabolic function and suppresses the rate of glycolysis against LPS. It is also found that overexpression of PRC decreases the transcriptional activity of NF-κB. These findings suggest that PRC is a negative regulator of endothelial inflammation.


Sudden death from ruptured intracranial vascular malformation.
Central nervous system (CNS) vascular malformations are well-known entities that may cause sudden death from rupture and intracranial hemorrhage. Despite this, relatively few papers deal with these lesions in the forensic literature. Here, we present four cases of sudden, non-traumatic death caused by ruptured CNS vascular malformations. In all four cases, the definitive source of bleeding was not identified grossly, being diagnosed only after relatively extensive histologic examination. When a source of intracranial hemorrhage is not readily identified at autopsy, it is common for forensic pathologists to rule the cause of death in such cases as "spontaneous intracerebral hemorrhage" or "spontaneous subarachnoid hemorrhage," depending on the location of the hemorrhage. Whether or not histologic evaluation is performed in such cases depends on pathologist preference or office policy, and may be influenced by limited available funding for such studies. Because vascular malformations are not always grossly visible at autopsy when accompanied by intracranial hemorrhage, we contend that it is important to thoroughly investigate the underlying cause of such hemorrhage through a meticulous gross examination as well as histologic examination. Such examination will lead to a more accurate assignment of the cause of death, which may have important implications for surviving family members, and will lead to a better understanding of the natural history of these intracranial lesions. A brief discussion of the histologic classification of CNS vascular malformations is provided.


Factors determining the abundance and distribution of rodents in a shrub-steppe ecosystem: the role of shrubs.
This study addressed the relative importances of shrub "resources" on a rodent community in a sagebrush dominated shrub-steppe ecosystem in southwestern Wyoming. Direct effects of shrubs (i.e., providing rodents with "food and cover") were assessed by removing shrubs from a 1.25 ha study plot and monitoring both rodent populations and their food resources. Shrub architecture and shrub-related food resources were found to be unimportant to deermice (Peromyscus maniculatus), Great Basin pocket mice (Perognathus parvus) northern grasshopper mice (Onychomys leucogaster) and Uinta ground squirrels (Spermophilus armatus), as shrub removal caused no significant changes in population sizes, sex ratios or age structure. Least chipmunks (Eutamias minimus) responded to shrub removal by leaving the plot and moving into adjacent shrubland. The montane vole (Microtus montanus) population showed a slight increase following shrub removal. Shrub removal did not alter the abundance of major rodent food resources on the plot (percent cover of herbaceous vegetation, soil seed reserves and ground-dwelling arthropods). Micrometeorological data suggested that shrubs did not significantly ameliorate a nocturnal rodent's micro-climate, but may have affected diurnal rodents' thermal loading rates by removing shade. While shrub architecture and food resources do not directly affect most of the rodents in this shrub-steppe ecosystem, shrubs may be important to rodents in a long-term time frame. Shrubs provide "safe sites" for germination and growth of herbaceous vegetation, thereby enhancing the diversity of the potential rodent food resources.


A pharmaco-fMRI study on pain networks induced by electrical stimulation after sumatriptan injection.
Sumatriptan, a drug widely used to alleviate migraine headaches, has several somatosensory adverse effects, including tactile allodynia. To understand whether sumatriptan affects sensory and affective circuitries simultaneously, we investigated the responses of 12 healthy volunteers to electrical stimuli after infusion with either sumatriptan or saline. Using a double-blind crossover study design, we used functional magnetic resonance imaging (fMRI) to measure brain activation in different areas during electrical stimulation. The visual analog scale (VAS) and short-form McGill pain questionnaire (SF-MPQ) were used to rate stimulation-evoked sensations and affections after drug administration. VAS rating, SF-MPQ, and block fMRI were all performed in each subject during sumatriptan and saline injection. Echo-planar imaging sequences were used to determine the whole-brain blood oxygenation level-dependent signal of the entire brain. Our results showed that sumatriptan predominantly activated regions in the medial pain system and smaller regions in the lateral pain system. These regions included the secondary somatosensory cortex (SII), anterior insular cortex, orbitofrontal cortex, medial thalamus, cerebellar supravermis, dentate nucleus, and the majority of the anterior cingulate cortex (ACC). In contrast, activation following saline administration was observed primarily in the lateral pain system, including the primary sensory cortex, lateral SII, posterior insular cortex, anterior ACC, and lateral thalamus. Importantly, we found that VAS ratings and MPQ scores were increased after sumatriptan infusion, but not after saline administration. Our fMRI, VAS, and SF-MPQ findings suggest that sumatriptan plays a significant role in the affective dimension of pain and a minor role related to sensory discrimination.


Preparation of highly concentrated and white cell-poor platelet-rich plasma by plateletpheresis.
Contaminating white blood cells (WBC) contribute remarkably to the overall growth factor content of locally applicable platelet-rich plasma (PRP) or platelet (PLT) gel and change the relative proportions of the contained growth factors. To study the independent effects of locally applicated highly concentrated PLTs, the development of preparations is needed that contain large amounts of PLTs and no or at least very few leucocytes. Therefore, 20 plateletpheresis procedures were performed in voluntary blood donors to get highly concentrated and extremely WBC-poor plateletpheresis concentrates. The degree of spontaneous PLT activation, the PLT aggregation response to agonists and the level of the growth factor TGF-beta1 (transforming growth factor beta1) were measured immediately after the donation and 1 day later. The concentrates contained 1.96 +/- 0.36 x 10e11 PLTs per unit in 55.2 +/- 7.9 ml, respectively. In comparison to the donors' blood, the PLT-enrichment factor was 15.3 +/- 5.4. At the same time, the concentrates contained extremely low residual numbers of WBCs (0.8 +/- 3.3 x 10e3/ml). The concentration of the growth factor TGF-beta1 was 743.2 +/- 243.9 ng/ml. On day 1, the PLT concentration and the TGF-beta1 content of the PLT concentrates had not decreased. In summary, plateletpheresis is suited to provide PRP products with higher concentrations of human platelets and platelet-derived growth factors than previously reported PRP preparation methods but with extremely low numbers of contaminating leucocytes.


Natural Killer Cells Contribute to Pathogenesis of Severe Alcoholic Hepatitis by Inducing Lysis of Endothelial Progenitor Cells.
Endothelial progenitor cells (EPCs) help in neovascularization and endothelial repair during injury. Patients with cirrhosis show increased number and function of EPCs in circulation. Since natural killer (NK) cells regulate EPCs, we investigated the relationship between the 2 in alcoholic cirrhosis (AC, n = 50) and severe alcoholic hepatitis (SAH, n = 18) patients and compared with nonalcoholic cirrhosis (n = 15) and healthy controls (HC, n = 30). Levels of systemic inflammatory cytokines were measured, and coculture assays were performed between EPCs and NK cells in contact-dependent and contact-independent manner. NK cell-mediated killing of EPCs was evaluated, and expression of receptors including fractalkine (FKN) on EPCs and its cognate receptor CX3CR1 on NK cells was studied by RT-PCR assays. Patients with SAH had higher regulated on activation, normal T cell expressed and secreted (RANTES) (p = 0.01), vascular endothelial growth factor (VEGF) (p = 0.04), IL-1β (p = 0.04), and IL-6 (p = 0.00) growth factors and proinflammatory cytokines as compared to AC and HC. Distinct populations of CD31+ CD34+ EPCs with low and high expression of CD45 were significantly lower in SAH than HC (CD45low , p = 0.03; CD45hi , p = 0.04) and AC (CD45low , p = 0.05; CD45hi , p = 0.02). SAH patients, however, showed increased functional capacity of EPCs including colony formation and LDL uptake. NK cells were reduced in SAH compared with AC (p = 0.002), however with higher granzyme ability (p < 0.001 and p = 0.04, respectively). In SAH, EPC-NK cell interaction assays showed that NK cells lysed the EPCs in both contact-dependent and contact-independent assays. Expression of interaction receptor CX3CR1 was significantly higher on NK cells (p = 0.0005), while its cognate receptor, FKN, was increased on EPCs in SAH patients as compared to HC (p = 0.0055). We conclude that in SAH, NK cells induce killing of EPCs via CX3CR1/FKN axis that may be one of the key events contributing to disease severity and proinflammatory responses in SAH.


Pancreatic Endocrine Effects of Dopamine Receptors in Human Islet Cells.
To date, there are no reports on the cellular localization of dopamine receptors in the human pancreas. In our study, we determined the localization and expression of 5 dopamine receptors (D(1), D(2), D(3), D(4), and D(5)) in normal human pancreas tissue. Human nonpathological pancreas tissues were fixed with 4% paraformaldehyde, paraffin-embedded, and processed for immunohistochemical analysis to detect dopamine receptors in the human pancreas tissue by using double immunofluorescent labeling and confocal microscopy. We found that the D(1) receptor is present in β cells; the D(2) receptor is expressed by α, δ, and pancreatic polypeptide cells; the D(4) receptor is expressed by β and polypeptide cells; whereas the D(5) receptor is expressed only by δ cells. Our results identify the dopamine receptors (D(1)-D(5)) in normal pancreas tissue and provide a morphological basis for studying the pancreatic endocrine effects of dopamine and suggest a new target for the clinical treatment of diabetes.


Posttranslational modifications regulate HIPK2, a driver of proliferative diseases.
The serine/threonine kinase homeodomain-interacting protein kinase (HIPK2) is a tumor suppressor and functions as an evolutionary conserved regulator of signaling and gene expression. This kinase regulates a surprisingly vast array of biological processes that range from the DNA damage response and apoptosis to hypoxia signaling and cell proliferation. Recent studies show the tight control of HIPK2 by hierarchically occurring posttranslational modifications such as phosphorylation, small ubiquitin-like modifier modification, acetylation, and ubiquitination. The physiological function of HIPK2 as a regulator of cell proliferation and survival has a downside: proliferative diseases. Dysregulation of HIPK2 can result in increased proliferation of cell populations as it occurs in cancer or fibrosis. We discuss various models that could explain how inappropriate expression, modification, or localization of HIPK2 can be a driver for these proliferative diseases.


A case report on a novel use of intraoperative Intrabeam™ radiation therapy for a recurrent malignant peripheral nerve sheath tumor with sciatic nerve involvement.
Malignant peripheral nerve sheath tumors (MPNST) are sarcomas that arise from peripheral nerves. They generally have a poor prognosis which is exacerbated by high local recurrence rates. This case report discusses the treatment of a patient with a MPNST with local recurrence. This case report is novel due to the use of intraoperative Intrabeam™ (Zeiss, Dublin, CA) radiation therapy use in the protection of neurovascular structures such as the sciatic nerve. The patient was a 65-year-old male who noticed a right posterior thigh mass slowly increasing in size over two months. A planned positive margin wide-resection excision was performed due to sciatic nerve abutment. The mass was determined to be a MPNST via postoperative pathology with positive margins along the sciatic nerve. The patient began adjuvant radiation therapy to the upper and lower thigh fields over a period of three months. Thirty-two months later, the patient was found to have a hypermetabolic mass with venous congestion and hyperemia at the prior surgical site which was confirmed by core needle biopsy to be local recurrence of the MPNST. Re-excision of the tumor was planned and performed followed by intraoperative Intrabeam™ radiation therapy. At two years of follow-up, the patient was doing well with minimal pain in his right buttock region with no new or recurrent neurological deficits. Radiologic imaging was negative for local recurrence of the MPNST. We believe this case report demonstrates a novel treatment strategy for sarcoma management. The unique use of intraoperative Intrabeam™ radiation therapy, which had not previously been used for this indication, may be efficacious in cases involving neurovascular structures. In this case, focal radiation from the intraoperative Intrabeam™ radiation device was used in a way to affect the recurrent tumor yet protect the sciatic nerve.


1H, 13C, 15 N backbone and side-chain NMR assignments for three MAX effectors from Magnaporthe oryzae.
Effectors are small and very diverse proteins secreted by fungi and translocated in plant cells during infection. Among them, MAX effectors (for Magnaporthe Avrs and ToxB) were identified as a family of effectors that share an identical fold topology despite having highly divergent sequences. They are mostly secreted by ascomycetes from the Magnaporthe genus, a fungus that causes the rice blast, a plant disease leading to huge crop losses. As rice is the first source of calories in many countries, especially in Asia and Africa, this constitutes a threat for world food security. Hence, a better understanding of these effectors, including structural and functional characterization, constitutes a strategic milestone in the fight against phytopathogen fungi and may give clues for the development of resistant varieties of rice. We report here the near complete 1H, 15 N and 13C NMR resonance assignment of three new putative MAX effectors (MAX47, MAX60 and MAX67). Secondary structure determination using TALOS-N and CSI.3 demonstrates a high content of β-strands in all the three proteins, in agreement with the canonic ß-sandwich structure of MAX effectors. This preliminary study provides foundations for further structural characterization, that will help in turn to improve sequence predictions of other MAX effectors through data mining.


Low-risk patients with chest pain and without evidence of myocardial infarction may be safely discharged from emergency department.
This study is an audit of the risk stratification of patients admitted to a university hospital emergency department with a suspected acute coronary syndrome (ACS). The main aim of the study was to investigate the prognosis of those patients who were discharged to home from the emergency room (ER) or adjacent chest pain observation unit (CPU). Three thousand one hundred and seven consecutive patients admitted to the ER with a suspected ACS were retrospectively identified. Seven hundred and sixty-four (25%) patients were discharged from the ER and 417 (13%) from the CPU after observation and ruling out myocardial infarction (MI) and high-risk ACS. One thousand seven hundred and two patients were hospitalized. Follow-up end-points were cardiovascular mortality, hospitalization for ACS and incidence of any cardiovascular disease event during 6 months. During 4 weeks after the discharge from the ER and CPU cardiovascular mortality was 0.1% and 0.5% and during 6 months 0.8% and 1.7%, respectively. Within 6 months 4.2% and 8.4% of the patients were hospitalized for ACS and 9.3% and 11.5% had a cardiovascular disease event. Patients admitted with chest pain may be safely discharged from the emergency department, if there is no evidence of MI or high-risk ACS. However, further examination and appropriate treatment must be arranged.


Cerebral hemodynamic and metabolic changes in fulminant hepatic failure: a retrospective study.
The purpose of this retrospective study was to determine cerebral hemodynamic and metabolic changes in comatose patients with fulminant hepatic failure. Computerized tomography of the brain and cerebral blood flow measurements by the xenon-computerized tomography scan or intravenous xenon-133 methods were obtained in 33 patients with fulminant hepatic failure. In a subgroup of 22 patients, arteriojugular venous oxygen content difference and cerebral metabolic rate for oxygen were determined. Carbon dioxide reactivity was tested in 17 patients, and intracranial pressure was recorded by an epidural monitor in 8 patients. Cerebral blood flow and arteriojugular venous oxygen content difference were adjusted to the average arterial carbon dioxide pressure of the sample (32 mm Hg). Adjusted cerebral blood flow varied from 16.5 to 94.7 ml/100 gm/min; 52% of the patients had reduced adjusted cerebral blood flows (less than 33 ml/100 gm/min), whereas 24% had hyperemic values (greater than 50 ml/100 gm/min). Patients with higher adjusted cerebral blood flows showed cerebral swelling on computerized tomography scan (p < 0.002), were in deeper coma (p < 0.05) and had greater mortality (p < 0.002). The adjusted arteriojugular venous oxygen content difference was negatively correlated with adjusted cerebral blood flow (r = -0.61, p < 0.002). The majority of patients with reduced adjusted cerebral blood flows had low adjusted arteriojugular venous oxygen content differences (less than 5 vol%), indicating hyperemia rather than ischemia. The average cerebral metabolic rate for oxygen was 50% of normal (1.6 +/- 0.4 ml/100 gm/min); even patients with low cerebral metabolic rates for oxygen recovered neurologically.(ABSTRACT TRUNCATED AT 250 WORDS)


Survival and recurrence after intraperitoneal chemotherapy use: Retrospective review of ovarian cancer hospital registry data.
Intraperitoneal/intravenous chemotherapy (IP/IV) was associated with improved survival for ovarian cancer (OC) patients in several randomized clinical trials. However, the uptake of IP/IV in clinical practice is varied due to conflicting evidence about its impact on survival and recurrence. The aim of this study was to explore the uptake of IP/IV treatment and to evaluate its impact on survival and recurrence in OC patients. Demographic and clinical information on OC patients (N = 2916) who underwent treatment for OC between 2000 and 2017 was obtained from the large healthcare system cancer registry. Duplicate records, grade 1, rare (eg, gelatinous carcinoma), and non-epithelial (eg, granulosa cell carcinoma) tumors were excluded. Kaplan-Meier survival curves were constructed to compare 5- and 10-year survival based on the chemotherapy type, surgery type, and stage. Multivariable Gray's piecewise constant time-varying coefficient models were fitted to evaluate the effect of IP/IV on adjusted hazard ratio (AHR) of OC survival and recurrence adjusting for potential confounders. The final sample consisted of 1846 OC patients, 14% (250/1846) of which received IP/IV chemotherapy. IP/IV was significantly associated with improved 10-year survival (P < .001). Multivariable Gray's model demonstrated that IP/IV therapy significantly reduced the AHR of death (AHR = 0.39-1.07, P < .001) with the beneficial effect gradually declining over time. Use of IP/IV chemotherapy had no impact on OC recurrence. These findings demonstrated that only a small fraction of eligible patients underwent IP/IV chemotherapy. We report a significant 10-year survival, but not necessarily recurrence benefit is associated with IP/IV chemotherapy compared to IV only, suggesting the need for novel ways of identifying patients who may benefit from IP/IV chemotherapy.


Shifting the Focus of Signaling Abnormalities in Colon Cancer.
Colon cancer tumorigenesis occurs incrementally. The process involves the acquisition of mutations which typically follow an established pattern: activation of WNT signaling, activation of RAS signaling, and inhibition of TGF-β signaling. This arrangement recapitulates, to some degree, the stem cell niche of the intestinal epithelium, which maintains WNT and EGF activity while suppressing TGF-β. The resemblance between the intestinal stem cell environment and colon cancer suggests that the concerted activity of these pathways generates and maintains a potent growth-inducing stimulus. However, each pathway has a myriad of downstream targets, making it difficult to identify which aspects of these pathways are drivers. To address this, we utilize the cell cycle, the ultimate regulator of cell proliferation, as a foundation for cross-pathway integration. We attempt to generate an overview of colon cancer signaling patterns by integrating the major colon cancer signaling pathways in the context of cell replication, specifically, the entrance from G1 into S-phase.


Carbon dioxide narcosis-induced apnea in a rat model of cardiac arrest and resuscitation.
In the clinical literature there are reports of patients failing to breathe and becoming comatose when supplied with 100% oxygen for respiratory distress. This effect has been attributed to a loss of respiratory drive. Recent studies have established that this explanation is incorrect, but have left the phenomenon unexplained. We propose that the apnea and coma reported is due to carbon dioxide narcosis. We have reproduced this effect in an animal model and have documented PCO2 values in excess of 250 mmHg during the apneic period. Our results suggest that this level of PCO2 suppresses both brainstem auditory evoked potentials and spontaneous respiration. The high PCO2 is due to inadequate gas exchange, and is easily remedied by provision of adequate ventilation.


Plasma immunoglobulin, total protein and albumin levels during Norplant use by Nigerian women.
To determine the effect of Norplant on plasma immunoglobulins, albumin and total proteins. A longitudinal prospective study of Norplant (six capsules) subdermal contraceptive implant acceptors. Family Planning Clinic, University College Hospital, Ibadan, Nigeria. 36 women volunteers aged 18-40 years on Norplant. Serum immunoglobulins, albumin and total protein before, one, three and 12 months after Norplant insertion. No statistically significant changes were observed in plasma levels of IgA, IgM and total proteins but plasma levels of IgG showed statistically significant increases after one, three and 12 months on Norplant. Norplant does not seem to alter IgM, IgA, albumin and total protein levels over a period of 12 months. It, however, induces significant changes in IgG levels at one, three and 12 months after insertion. These changes are less marked by the end of 12 months.


Luminescent carbon nanoparticles separation and purification.
Nowadays luminescent carbon-based nanoparticles can be synthesized by a wide range of physical and chemical methods from a large variety of carbon-based sources. However, in most of the cases the product of synthesis is a complex mixture of compounds, which results in significant challenges in understanding the structure and optical properties of the reaction products. Consequently, a number of separation and purification methodologies have been developed to alleviate these challenges. In this review, we provide a detailed analysis of the current state of the art for methods of luminescent carbon nanoparticles separation and purification. We specifically target such methods as sucrose density gradient centrifugation, chromatography techniques, and electrophoresis because of their ability for fine separation of the reaction products with into a number of fractions. The aim of our comparative analysis is to help development of future strategies for reaction product separation and purification leading to a better understanding of carbon nanoparticles structure and luminescent mechanism as well as to underpin their applications.


Deceiving SARS-CoV-2 molecular-tropism clues - A combinational contemporary strategy.
Several attempts to control the dreadfulness of SARS-CoV-2 are still underway. Based on the literature evidences we have speculated a prospective contemporary remedy, which was categorized into Specificity, Remedy, and a Conveyor. In which, pros and cons were discussed and inferred the possible alternatives. (a) Specificity: Implicit to express the ACE2 receptors in conveyor cells to deceive SARS-CoV-2 frompreponetargets. (b) Remedy: As depletion of pulmonary surfactants causes strong acute respiratory distress syndrome, we propose an entity of a cost-effective artificialsurfactantsystem as a remedy to pulmonary complications. (c) Conveyor: We propose red blood cells (RBCs) as a conveyor with embedded artificial surfactant and protruding ACE2 receptors for the target-specific delivery. Overall we postulate focused insights by employing a combinational contemporary strategy to steer towards a prospective direction on combating SARS-CoV-2.


Development, reactivity and GFA immunofluorescence of astroglia-containing monolayer cultures from rat cerebrum.
This report describes detailed protocols for the dissociation, seeding and growth in vitro of monolayer cultures derived from neonatal rat cerebrum. Primary cultures derived by using different seeding densities and in vitro ages were examined qualitatively and quantitatively for morphological composition in terms of two major cell classes (flat cells and process-bearing cells) and for the presence within these classes of glial fibrillary acidic protein (GFA) as detected by immunofluorescence histochemistry. Also examined was the reaction of the cells to serum withdrawal plus the administration of dibutyryl cyclic AMP in terms of the conversion of flat cells into process-bearing cells. Conditions are defined for the generation of in vitro cell populations, more than 90% of which are GFA-containing flat cells which can all be experimentally converted into cells with processes. These well-defined culture preparations will serve as useful models for future studies of astroglial behaviour.


NLRP12 attenuates ozone-induced pulmonary inflammation by regulating canonical NF-κB Pathway.
Ozone (O3) is an important urban air pollutant having strong correlations with respiratory diseases. Several lines of evidence suggest that O3 exposure causes airway hyperresponsiveness (AHR) and pulmonary inflammation. Inhibitory innate immune receptors, such as NLRP12, have been demonstrated to alleviate inflammation, but the functional role for NLRP12 in O3-induced lung inflammatory inflammation remains to be reported. Here, we determined whether NLRP12 took a protective role in O3-induced AHR and pulmonary inflammation via the suppression of canonical NF-κB. C57BL/6 J mice were exposed to filtered air (FA) or 0.25, 0.50 and 1.00 ppm (3 h/day for 5 consecutive days) followed by detection of airway resistance, white blood cells, total proteins, and cytokines. Meanwhile, NLRP12 in lung tissue were detected by real time PCR. Moreover, we also examined protein expression of NLRP12 and key biomarkers of NF-κB pathway. It was shown that 24 h post O3 exposure, AHR as wells as total cells, proteins, and cytokines contents in BALF of mice were increased compare to those of FA controls in a dose-dependent manner. Notably, O3-induced AHR and lung inflammation were associated with significant decrease in pulmonary NLRP12 and upregulation of phosphorylated IRAK1, p65 and IκBα in canonical NF-κB pathway. Intratracheal administration of NLRP12-overexpresing adenovirus 4 days prior to O3 exposure alleviated AHR and lung inflammation, and inhibited canonical NF-κB pathway activation. The findings from this study indicate that NLRP12 attenuates O3-induced AHR and pulmonary inflammation, possibly through regulating canonical NF-κB pathway. This provides a novel target for the prevention and treatment of lung diseases induced by O3 exposure.


Beneficial effects of adding magnesium to desalinated drinking water on metabolic and insulin resistance parameters among patients with type 2 diabetes mellitus: a randomized controlled clinical trial.
There is evidence that increasing the consumption of water containing magnesium can improve glucose metabolism and insulin resistance in patients with type 2 diabetes mellitus (T2DM). This trial was undertaken with the objective of evaluating the effect of adding different concentrations of magnesium chloride to the desalinated drinking water on the glycemic, metabolic, and insulin resistance parameters among patients with T2DM. A randomized cross-sectional controlled clinical trial was conducted to evaluate the effects of adding magnesium chloride supplement to desalinated drinking water consumed by patients with T2DM on the glycemic and metabolic parameters and indicators of insulin sensitivity. The total number of patients with T2DM who successfully completed the trial is 102. Patients were randomly allocated into three groups: the first group received bottled water without added magnesium (0 mg/L) (Group A, n = 37); the second group received bottled water with a low level of magnesium (20 mg/L) (Group B, n = 33); and the third group received drinking water with a high level of magnesium (50 mg/L) (Group C, n = 32). The daily consumption of elemental magnesium for a period of 3 months resulted in significant improvement in HbA1C (8.0 vs 8.2%, p = 0.04), insulin level (7.5 vs 9.9 μIU/mL, p = 0.03), and homeostasis model assessment-estimated insulin resistance (HOMA.IR) (2.5 vs 2.9, p = 0.002) in group C. However, there was no significant improvement in fasting blood glucose (FBS) level or lipid profile. The results of this study suggest that oral magnesium supplementation at the given dose of 50 mg/L daily added to drinking water could improve long-term glycemic control indicators and reduce insulin resistance in patients with T2DM.


IF-combined smRNA FISH reveals interaction of MCPIP1 protein with IER3 mRNA.
MCPIP1 and IER3 are recently described proteins essential for maintenance of immune homeostasis. IER3 is involved in the regulation of apoptosis and differentiation and has been shown lately to protect activated T cells and macrophages from apoptosis. MCPIP1 is an RNase critical for controlling inflammation-related mRNAs. MCPIP1 interacts with and degrades a set of stem-loop-containing mRNAs (including IL-6). Our results demonstrate the involvement of MCPIP1 in the regulation of IER3 mRNA levels. A dual luciferase assay revealed that over-expression of MCPIP1 resulted in a decrease of luciferase activity in the samples co-transfected with constructs containing luciferase CDS attached to IER3 3'UTR. We identified a stem-loop structure similar to that described to be important for destabilization of the IL-6 mRNA by MCPIP1. Examination of IER3 3'UTR sequence, structure and evolutionary conservation revealed that the identified stem-loop is buried within a bigger element. Deletion of this fragment abolished the regulation of IER3 3'UTR-containing transcript by MCPIP1. Finally, using immunofluorescence-combined single-molecule RNA FISH we have shown that the MCPIP1 protein co-localizes with IER3 mRNA. By this method we also proved that the presence of the wild-type NYN/PIN-like domain of MCPIP1 correlated with the decreased level of IER3 mRNA. RNA immunoprecipitation further confirmed the interaction of MCPIP1 with IER3 transcripts in vivo.


Centric fission of chromosome 7 with 47,XX,del(7)(pter----cen::q21----qter)+cen fr karyotype in a mother and proximal 7q deletion in two malformed newborns.
In the present paper we report a characteristic pattern of external and internal malformations in two male siblings with proximal 7q interstitial deletion as the unbalanced product of a rearranged chromosome 7 in the mother with karyotype 47,XX,del(7)(pter----cen::q21----qter),+fr. The interstitial 7q deletion in the mother included centromeric fission, break at 7q21 and preservation of the proximal q arm fragment.


Searching for optimal blood pressure targets in type 2 diabetic patients with coronary artery disease.
Controversies exist regarding the optimal blood pressure (BP) level that is safe and provides cardiovascular protection in patients with type 2 diabetes mellitus (T2DM) and coexistent coronary artery disease. Several new glucose-lowering agents have been found to lower BP as well, making the interaction between BP and T2DM even more complex. With the reference to recent literature, this review article describes the potential mechanisms of increased risk of hypertension in T2DM and outlines the possible optimal BP levels based upon recommendations on the management of hypertension by the current guidelines, in combination with our research findings, for type 2 diabetic patients with coronary artery disease. The development of hypertension in T2DM involves multiple processes, including enhanced sympathetic output, inappropriate activation of renin-angiotensin- aldosterone system, endothelial dysfunction induced through insulin resistance, and abnormal sodium handling by the kidney. Both AGE-RAGE axis and adipokine dysregulation activate intracellular signaling pathways, increase oxidative stress, and aggravate vascular inflammation. Pancreatic β-cell specific microRNAs are implicated in gene expression and diabetic complications. Non-pharmacological intervention with lifestyle changes improves BP control, and anti-hypertensive medications with ACEI/ARB, calcium antagonists, β-blockers, diuretics and new hypoglycemic agent SGLT2 inhibitors are effective to decrease mortality and prevent major adverse cardiovascular events. For hypertensive patients with T2DM and stable coronary artery disease, control of BP < 130/80 mmHg but not < 120/70 mmHg is reasonable, whereas for those with chronic total occlusion or acute coronary syndromes, an ideal BP target may be somewhat higher (< 140/90 mmHg). Caution is advised with aggressive lowering of diastolic BP to a critical threshold (< 60 mmHg). Hypertension and T2DM share certain similar aspects of pathophysiology, and BP control should be individualized to minimize adverse events and maximize benefits especially for patients with T2DM and coronary artery disease.


The Y137H mutation of VvCYP51 gene confers the reduced sensitivity to tebuconazole in Villosiclava virens.
Management of rice false smut disease caused by Villosiclava virens is dependent on demethylation inhibitor (DMI) fungicides. Investigation of molecular mechanisms of resistance is therefore of upmost importance. In this study the gene encoding the target protein for DMI fungicides (VvCYP51) was cloned and investigated. The VvCYP51 gene in the resistant mutant revealed both a change from tyrosine to histidine at position 137 (Y137H) and elevated gene expression compared to the parental isolate. In order to determine which of these mechanisms was responsible for the reduced sensitivity to DMI fungicide tebuconazole, transformants expressing the mutated or the wild type VvCYP51 gene were generated. Transformants carrying the mutated gene were more resistant to tebuconazole compared to control transformants lacking the mutation, but the expression of the VvCYP51 gene was not significantly correlated with EC50 values. The wild type VvCYP51 protein exhibited stronger affinity for tebuconazole compared to the VvCYP51/Y137H in both molecular docking analysis and experimental binding assays. The UV-generated mutant as well as transformants expressing the VvCYP51/Y137H did not exhibit significant fitness penalties based on mycelial growth and spore germination, suggesting that isolates resistant to DMI fungicides based on the Y137H mutation may develop and be competitive in the field.


An iridoid and a flavonoid from Sideritis lanata L.
A new iridoid diglucoside, 10-O-(E)-p-coumaroylmelittoside (1) and a new flavone glucoside, O-(6''-O-Acetyl-)-beta-glucopyranosylchrysoeriol (2), together with four known flavone glycosides, were isolated from the aerial parts of Sideritis lanata. The structures of the new compounds were elucidated by spectroscopic methods, 2D NMR and MS.


A potential mechanism for extracellular matrix induction of breast cancer cell normality.
Extracellular matrix proteins from embryonic mesenchyme have a normalizing effect on cancer cells in vitro and slow tumor growth in vivo. This concept is suggestive of a new method for controlling the growth and spread of existing cancer cells in situ and indicates the possibility that extracellular proteins and/or embryonic mesenchymal fibroblasts may represent a fertile subject for study of new anti-cancer treatments.


Fragile X Mental Retardation Protein and Dendritic Local Translation of the Alpha Subunit of the Calcium/Calmodulin-Dependent Kinase II Messenger RNA Are Required for the Structural Plasticity Underlying Olfactory Learning.
In the adult brain, structural plasticity allowing gain or loss of synapses remodels circuits to support learning. In fragile X syndrome, the absence of fragile X mental retardation protein (FMRP) leads to defects in plasticity and learning deficits. FMRP is a master regulator of local translation but its implication in learning-induced structural plasticity is unknown. Using an olfactory learning task requiring adult-born olfactory bulb neurons and cell-specific ablation of FMRP, we investigated whether learning shapes adult-born neuron morphology during their synaptic integration and its dependence on FMRP. We used alpha subunit of the calcium/calmodulin-dependent kinase II (αCaMKII) mutant mice with altered dendritic localization of αCaMKII messenger RNA, as well as a reporter of αCaMKII local translation to investigate the role of this FMRP messenger RNA target in learning-dependent structural plasticity. Learning induces profound changes in dendritic architecture and spine morphology of adult-born neurons that are prevented by ablation of FMRP in adult-born neurons and rescued by an metabotropic glutamate receptor 5 antagonist. Moreover, dendritically translated αCaMKII is necessary for learning and associated structural modifications and learning triggers an FMRP-dependent increase of αCaMKII dendritic translation in adult-born neurons. Our results strongly suggest that FMRP mediates structural plasticity of olfactory bulb adult-born neurons to support olfactory learning through αCaMKII local translation. This reveals a new role for FMRP-regulated dendritic local translation in learning-induced structural plasticity. This might be of clinical relevance for the understanding of critical periods disruption in autism spectrum disorder patients, among which fragile X syndrome is the primary monogenic cause.


Electrophysiology of a chick neuronal nicotinic acetylcholine receptor expressed in Xenopus oocytes after cDNA injection.
Brain nicotinic acetylcholine receptors (nAChRs) are made up of protein subunits that differ from those constituting muscle nAChRs. To characterize the physiological properties of one class of avian brain nicotinic receptor, we injected the nuclei of Xenopus oocytes with full-length cDNAs for the ligand binding (alpha 4) and structural (n alpha) subunits. Injected oocytes had large ACh-induced currents in the microampere range that were insensitive to alpha-bungarotoxin, as expected for neuronal nAChRs. We found that these brain nAChRs incorporate at least two alpha 4 subunits and that their functional properties differ from muscle nAChRs in at least two respects: the elementary conductance is considerably smaller (20 pS), and channels in outside out patches stop functioning within a few minutes.


Energetics of protein translocation into mitochondria.
Biogenesis of mitochondria depends on the coordinated action of at least six protein translocases present in both mitochondrial membranes. They use different energy sources to drive unidirectional transport of proteins across and into mitochondrial membranes. Here we present an overview on the energetic requirements of different mitochondrial import pathways.


Malaria vaccine: immunization of mice with a synthetic T cell helper epitope alone leads to protective immunity.
The immunogenicity of the non-repetitive sequences of the Plasmodium berghei circumsporozoite (CS) protein was studied using synthetic peptides. Two CS sequences (residues 20-39 and 57-70) exhibiting T cell helper activity were identified. Immunization of BALB/c mice with a branched peptide containing either the 20-39 or the 57-70 sequence and two repeats (B epitope) in a linear sequence induced high titers of anti-repeat and anti-sporozoite antibodies. Mice immunized with the T-B construct (high antibody titers) or with the 57-70 epitope alone (no serum anti-repeat or anti-peptide antibodies) were protected to a similar degree after challenge with infective sporozoites. No protection was obtained in mice immunized with the 20-39 epitope. These results indicate that BALB/c mice can be protected either by effector T cells or by high levels of anti-repeat antibodies. Thus, in the same strain, a double mechanism of protection can be obtained by a synthetic peptide vaccine.


Effects of long-term psychological intervention on blood pressure and health-related quality of life in patients with hypertension among the Chinese working population.
The aim of this study was to analyze the effects of psychological intervention on blood pressure, health-related quality-of-life (HRQOL), and stroke prevalence in patients with hypertension among the Chinese working population. Cluster sampling was conducted in September 2013 at the Shaanxi Jinduicheng Molybdenum Group General Hospital (intervention group) and the Shaanxi Province Hancheng Mining Bureau General Hospital (control group). The intervention group received regular psychological intervention for 2 years, including cognitive, emotional, and behavioral interventions. HRQOL was measured with the Spanish Hypertension Quality of Life Questionnaire (MINICHAL). We analyzed the data from a total of 409 subjects. After 2 years of psychological intervention, systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the non-anxiety subgroup, and the anxiety subgroup were lower than baseline levels and lower than those in the control group. Post intervention, the mental state, somatic symptoms, and total MINICHAL scores were significantly below baseline levels, and the stroke morbidity was lower than that in the control group. Post intervention, SBP, DBP, and the MINICHAL scores in the intervention group were lower than those in the control group. SBP, DBP, and the MINICHAL scores were lower in the intervention group after 1 and 2 years of psychological intervention, as compared with the control group. Long-term psychological intervention can thus be used as an adjunctive therapy for patients with hypertension among the Chinese working population to improve their blood pressure, HRQOL and stroke prevalence.


Low linoleic acid may facilitate Δ6 desaturase activity and docosahexaenoic acid accretion in human fetal development.
The n-3 and n-6 fatty acids are transferred across the placenta with consistently higher 22:6n-3 and lower 18:2n-6 in fetal than maternal plasma. This study sought to determine whether maternal and fetal cord blood red blood cell (RBC) phospholipid fatty acids show similar saturation with 22:6n-3, and also addressed the relationship between 18:2n-6 and Δ6 desaturase product/precursor ratios for 97 mothers and newborns. Despite higher fetal than maternal plasma phospholipid 22:6n-3, the maternal and fetal RBC phospholipid 22:6n-3 showed similar curvilinear relationships to the plasma phospholipid 22:6n-3. Risk of failure to achieve high RBC phospholipid 22:6n-3 increased sharply below a plasma phospholipid 22:6n-3 of 6.5g/100g fatty acids. Higher maternal and fetal 18:2n-6 was associated with lower RBC phospholipid 22:6n-3/22:5n-3, 22:5n-6/22:4n-6 and 18:3n-6/18:2n-6. These findings suggest low placental transfer of 18:2n-6 may be a specific mechanism to prevent inhibition of fetal Δ6 desaturase and facilitate fetal cellular phospholipid 22:6n-3 accretion.


Clinical and genetic characteristics in patients with Huntington's Disease from Argentina.
Huntington's Disease (HD) is a neurodegenerative disease, caused by the expansion of an unstable (CAG)(n) in the HTT gene. There is scarce data about the disease in Argentina. To describe the demographic, clinical and molecular data in patients with HD from Argentina. 59 HD patients were recruited at our department. Comprehensive interviews, neurological examination and genetic analysis were performed in probands. Statistical analysis was conducted using G-Stat 2.0 and non-parametric tests (Wilcoxon). 32 women and 27 men were diagnosed with a mean age of 45.7 ± 16.2 years and a mean age at onset of 35.8 ± 14.8 years. We found no gender prevalence and an inverse correlation between size of mutant CAG repeat sequence and age at onset, r = -0.58, r(2) = 33.6, Pearson's correlation coefficient p = 0.0008. Juvenile HD in this series of patients was higher than previously reported (16.6% vs. <10%). The mean CAG repeat in the expanded allele was 45.1. The number of CAG repeats in Argentinean controls was 17.8, which is similar to the literature of the European population. This is the first series of Argentinean HD patients with demographic, clinical and molecular data. Our findings appear similar to the ones described in Western European populations.


Expression of the third intracellular loop of the delta-opioid receptor inhibits signaling by opioid receptors and other G protein-coupled receptors.
To explore the feasibility of developing inhibitors of signaling by opioid receptors and other G protein-coupled receptors (GPCRs) that use the same G protein pool, we investigated the capacity of a minigene encoding the third intracellular loop of the delta-opioid receptor (delta-i3L) to act as competitive antagonist of the receptor-G protein interface interaction. In delta-i3L-expressing cells, the peptide blocked high-affinity agonist binding to both the delta- and the mu-opioid (delta-OR and mu-OR) and attenuated opioid and alpha2-adrenergic receptor (alpha2AR)-dependent [35S]guanosine-5'-O-(3-thio)triphosphate binding. Furthermore, delta-i3L expression resulted in inhibition of delta-, mu-OR-, and alpha2AR-receptor-mediated cAMP accumulation, whereas the cAMP response produced by activation of the beta2-adrenergic receptor was unaffected, suggesting that the inhibitory effects of delta-i3L expression were selective for Gi/Go proteins. Moreover, although delta-i3L expression also attenuated drastically phospholipase C accumulation and Ca2+ release following mu- and delta-OR stimulation, it failed to inhibit carbachol-mediated stimulation of inositol phosphate accumulation in M1-muscarinic receptor-expressing human embryonic kidney 293 cells. Finally, we also examined the effects of delta-i3L expression on the regulation of the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase pathway. Our results demonstrate that, although ERK activation by mu- and delta-ORs is attenuated by the presence of delta-i3L, ERK activation mediated by alpha2AR remained unaffected. Collectively, our data demonstrate that the delta-i3L can be used as potent inhibitor of G protein signaling for various GPCRs that use a common pool of G proteins.


Seasonal influences on admissions for mood disorders and schizophrenia in a teaching psychiatric hospital in Egypt.
Distinct seasonal variation in hospital admission and various associations with the climatic parameters for mood disorders and schizophrenia have been previously reported in several world regions. There are, however, no North-African studies on this association. The charts of 1987 patients with mood disorders (mania 1181, depression 806) and 1359 patients with schizophrenia admitted from 2003 to 2007 from an university hospital at Mansoura, Egypt, were reviewed. Seasonality was assessed with Cosinor Analysis. Correlations of the rate of admissions for affective disorders and schizophrenia to climatic variables were performed, including lagged and differenced data. There was a significant seasonal variation in the monthly admission frequencies both for mania (peak in June) and for depression (peak in December) but no significant seasonal variation was found in admissions with diagnosis of schizophrenia. The number of admissions for mania was positively correlated to indicators of temperature and luminosity, but inversely correlated to relative humidity. Quite the opposite, the number of admissions for depression showed a negative correlation to temperature and luminosity, but a positive correlation to relative humidity. 55-57% of the monthly variance of the number of admissions for mood disorders was explained by climatic variables. Seasonality of admissions for mood disorders, but not for schizophrenia, has been demonstrated, in an African Mediterranean region with a fairly constant climate. The association between admission rates and climatic variables found in this study could pave the way for further studies aiming at exploration of the biological mechanism of this association as well as tailoring of treatment interventions on mood disorders.


Antiviral polysaccharide and antiviral peptide delivering nanomaterials for prevention and treatment of SARS-CoV-2 caused COVID-19 and other viral diseases.
Antiviral peptides and antiviral polysaccharides can play a major role in the prevention and treatment of emerging viral health problems. These antiviral compounds are biocompatible, environmentally friendly, non-toxic, and cost-effective, yet are poorly water soluble and vulnerable to enzymatic (protease) degradation within the aggressive intercellular microenvironment. Therefore, they should be properly protected and delivered to viruses and host cells by the well-designed nanocarriers that mimic viruses in terms of size, morphology, and smart function. This literature review is meant to introduce the latest advances (mainly within the past five years) in antiviral nano-assemblies comprising antiviral peptides or antiviral polysaccharides. To the best of our knowledge, there is no similar study in the literature that has solely and sufficiently investigated such antiviral nanomaterials partially or totally derived from nature. The rational classification of microorganism-, plant-, and animal-derived antiviral polysaccharide and antiviral peptide delivering nanomaterials and exploration of their relevant applications will clarify the promising capacity of these state-of-the-art materials for a number of technologies developed to inactivate viruses.


The chemotherapeutic drug carboplatin affects macrophage responses to LPS and LPS tolerance via epigenetic modifications.
Following re-exposure to lipopolysaccharide (LPS), macrophages exhibit an immunosuppressive state known as LPS tolerance, which is characterized by repressed proinflammatory cytokine production. LPS-induced tolerance in macrophages is mediated in part by epigenetic changes. Carboplatin, an anticancer chemotherapeutic drug, exerts its effect by inhibiting DNA replication and transcription, as well as through epigenetic modifications. Through an unbiased screen, we found that carboplatin rescued TNF-α and IL-6 production in LPS-tolerant macrophages. Transcriptomic analysis and gene set enrichment analyses revealed that p53 was one of the most significantly upregulated hallmarks in both LPS-primed and LPS-tolerant macrophages in the presence of carboplatin, while E2F and G2/M were the most negatively regulated hallmarks. Heterochromatin protein 1 (HP1-α), which is associated with gene silencing, was significantly reduced in carboplatin-treated LPS-tolerant macrophages at the mRNA and protein levels. Dynamic changes in the mRNA level of genes encoding H3K9me3 methyltransferases, setdb2, kdm4d, and suv39h1 were induced in the presence of carboplatin in LPS-tolerant macrophages. Taken together, we provide evidence that carboplatin treatment interferes with proinflammatory cytokine production during the acute LPS response and LPS tolerance in macrophages, possibly via H3K9me3 modification.


Reverse cholesterol transport, high density lipoproteins and HDL cholesterol: recent data.
Unlike LDL cholesterol, which is a major cardiovascular risk factor, HDL cholesterol plays an important anti-atherogenic role through reverse cholesterol transport from peripheral cells to the liver. Some recent biochemical and epidemiological data shed light on this key function. In the hereditary Tangier disease with disseminated lipid storage, the main biochemical feature is a dramatically low level of HDL cholesterol. Different mutations in the ATP-binding cassette transporter A1 (ABCA1) gene have been recently described, which interfere with cellular cholesterol efflux. This results in low HDL plasma level, and defective reverse cholesterol transport to the liver. Moreover, selective hepatic uptake of HDL cholesteryl esters by SR-B1, a class B scavenger receptor, also plays a key role. In the follow-up of the PROCAM Study, the relative risk of coronary events is high in a cluster of patients with increased total cholesterol/HDL-cholesterol ratio. In the prospective secondary prevention VA-HIT study, the relative risk of coronary events in patients with low HDL cholesterol levels is decreased of 22% with a treatment by gemfibrozil. If the present available range of drugs targeted at increasing HDL cholesterol levels is rather narrow, future therapies will be encouraging, especially with agonists of PPARs.


[Nutritional deficiencies and supplementation after metabolic surgery].
Increasing prevalence of morbid obesity in Germany is associated with an increasing number of bariatric surgical interventions.Based on the effectiveness of bariatric surgery with regard to a significant reduction of body weight and comorbidity as well as improvement of the quality of life compared with conservative measures, its value and impact has been substantially increased. Long-term metabolic deficits such as nutrient deficiencies can be considered the main risks of various restrictive, combined and malabsorptive procedures of bariatric surgery.The aim of this overview is to characterize metabolic complications after bariatric surgery and their prophylaxis, which require a temporary or permanent surveillance and, if necessary, effective supplementation.Bariatric surgical interventions such as gastric banding (GB) and sleeve gastrectomy (SG) can be subsequently associated with deficiencies related to B‑vitamins whereas iron, folate, and vitamins B1, B12 and D deficiencies might be consequences of malabsorptive procedures such as biliopancreatic diversion, duodenal switch and Roux-en-Y gastric bypass.Due to possible metabolic and surgical complications after bariatric surgery, patients need to undergo life-long follow-up investigations. The currently available guidelines of the American Association of Bariatric and Metabolic Surgery are the basis for the latest recommendations on supplementation and treatment in bariatric surgery.


Religion and delusion.
We review scholarship that examines relationships - and distinctions - between religion and delusion. We begin by outlining and endorsing the position that both involve belief. Next, we present the prevailing psychiatric view that religious beliefs are not delusional if they are culturally accepted. While this cultural exemption has controversial implications, we argue it is clinically valuable and consistent with a growing awareness of the social - as opposed to purely epistemic - function of belief formation. Finally, we review research on continuities between religious and delusional cognition, which reveals that religious content is quite common in delusions and which provides tentative evidence for a positive relationship between religious belief and delusion-like belief in the general population.


Neurostimulation in chronic cluster headache.
About 1% of all chronic cluster headache patients become intractable (iCCH; ie, they are refractory to adequate regimens of all established preventive drugs). Various lesional interventions have been attempted in these patients, none with lasting benefits. In recent years, nondestructive neurostimulation methods have raised new hope. Hypothalamic deep brain stimulation (hDBS) acts rather rapidly and has durable efficacy, but it is not without risk. Occipital nerve stimulation (ONS) was studied in two trials that included 17 iCCH patients. Clinical efficacy was found to be very satisfactory by most patients and investigators. Although slightly less efficacious than hDBS, ONS has the advantage of being harmless and reversible. At this stage, it should be the preferred first-line invasive therapy for iCCH. Recent case reports mention efficacy of supraorbital and vagus nerve stimulation. Whether these neurostimulation methods have a place in the management of iCCH patients remains to be determined.


Biocatalytic synthesis of intermediates for the synthesis of chiral drug substances.
There has been an increasing awareness of the enormous potential of microorganisms and enzymes for the transformation of synthetic chemicals with high chemo-, regio- and enantioselectivity. Chiral intermediates and fine chemicals are in high demand, both from the pharmaceutical and agrochemical industries, for the preparation of bulk drug substances and agricultural products. Biocatalytic processes have been described for the synthesis of chiral intermediates for beta3- and beta2-receptor agonists, antihypertensive drugs, antiviral agents, melatonin receptor agonists, anticholesterol and anticancer drugs, and drugs to treat Alzheimer's disease.


Green tea consumption and serum malondialdehyde-modified LDL concentrations in healthy subjects.
Green tea was shown to inhibit LDL oxidation, platelet aggregation, and matrix metalloproteinases (MMPs) activities in vitro. We tried to elucidate whether or not green tea consumption may have these effects in vivo, which may be protective against atherosclerotic disease. We measured serum malondialdehyde-modified LDL (MDA-LDL) concentrations and urine 8-epi-prostaglandin (PG) F(2alpha) in 22 healthy male nonsmokers. They drank 7 cups/day of water for 2 weeks and drank 7 cups/day of green tea for the next 2 weeks. Regarding platelet aggregation, plasma thromboxane B(2) (TXB(2)) and 6-keto-PGF(1alpha) concentrations and ex vivo platelet aggregation were evaluated. Plasma MMP-2 and -9 concentrations were also measured. Of the 22 subjects, 20 had been in the habit of drinking green tea before the study. Plasma catechins concentrations significantly decreased at the end of the water period and then increased at the end of the green tea period. Although no change in plasma LDL-cholesterol concentrations (110 +/- 33 vs. 113 +/- 28 mg/dL, p = NS) was found, MDA-LDL concentrations (84 +/- 45 vs. 76 +/- 40 IU/L, p < 0.05) and the ratio of MDA-LDL/LDL-cholesterol (0.74 +/- 0.21 vs. 0.65 +/- 0.20, p < 0.02) significantly decreased at the end of the green tea period. However, no significant changes were observed in urine 8-epi-PGF(2alpha) concentrations, in platelet aggregation, nor in plasma TXB(2), 6-keto-PGF(1alpha) or MMP concentrations. Daily consumption of green tea decreased serum MDA-LDL concentrations, but it had no significant effects on platelet aggregation, platelet TX production or plasma MMPs concentrations. Our results suggest that green tea consumption may inhibit LDL oxidation in vivo.


Concha-Type Microtia: New Surgical Incision.
Reconstruction of auricles for conchal-type microtia is challenging but rewarding. Many plastic surgeons consider autogenous rib cartilage as the standard material for framework fabrication. A healthy, scar-free skin envelope and a defined cartilaginous framework are also critical to successful ear reconstruction. The aim of this study was to improve the outcome of the reconstruction and minimize complications by proposing a new surgical incision. Thirty-three patients who underwent auricular reconstruction of concha-type microtia of various etiologies with the new skin flap incision between 2017 and 2022 were included in the study. Patients' clinical data, detailed surgical techniques, and postoperative care were recorded. Thirty-three patients (21 male, 12 female) were enrolled in the study. The mean age of the patients was 21.51 years at the time of reconstruction. The microtia was on the right side in 17 cases, on the left side in 12 cases, and 4 cases were bilateral; 12 cases were traumatic amputations of the helical component of the auricle, 11 cases were deformities after a burn, and 10 cases were congenital. The mean follow-up time was 17.43 months. A good initial projection without obvious scarring on the anterior surface of the auricle was achieved, with an overall complication rate of 5.42%. The surgical incision recommended in the study improves the final aesthetic result of the technique without any additional surgical risk.


[Intravitreal triamcinolone acetonide for the treatment of intraocular edematous and neovascular diseases].
Within the last 2 years, intravitreal application of triamcinolone acetonide has exponentially increased as a treatment option for various intraocular neovascular and edematous proliferative disorders. The best response to intravitreal triamcinolone acetonide injection in terms of gain in visual acuity was obtained for eyes with intraretinal edematous diseases such as diffuse diabetic macular edema, branch retinal vein occlusion, central retinal vein occlusion, and pseudophakic cystoid macular edema. Visual acuity increased and degree of intraocular inflammation decreased in eyes with various types of noninfectious uveitis including sympathetic ophthalmia. Intravitreal triamcinolone may be useful as angiostatic therapy in eyes with iris neovascularization and proliferative ischemic retinopathies. Possibly, intravitreal triamcinolone may be helpful for exudative age-related macular degeneration, alone or in combination with photodynamic therapy. In eyes with chronic, therapy-resistant, ocular hypotony, intravitreal triamcinolone can induce an increase in intraocular pressure and may stabilize the eye. The complications of intravitreal triamcinolone therapy, such as secondary ocular hypertension in about 40% of the eyes injected, cataractogenesis, postoperative infectious and noninfectious endophthalmitis, and pseudo-endophthalmitis will be covered in another article. Intravitreal triamcinolone injection can be combined with other intraocular surgeries including cataract surgery. Cataract surgery performed some months after the injection did not show a markedly elevated rate of complications. If vision increases after the intravitreal triamcinolone injection, the injection can be repeated. The duration of the effect of a single intravitreal injection of triamcinolone ranges between 2 and 9 months, probably depending on the dosage used. Intravitreal triamcinolone acetonide may offer a possibility for adjunctive treatment of intraocular oedematous and neovascular disorders. One has to take into account the side effects and the lack of long-term follow-up observations.


The role of crosstalk in dual-task performance: evidence from manipulating response-code overlap.
The present study examined the role of crosstalk in dual-task interference using a combination of a nonspeeded visual task and an auditory-manual reaction time (RT) task. The potential for dual-task crosstalk was introduced by presenting in the visual task objects (e.g., a cup with a handle), which "afford" associated responses that were either spatially compatible or incompatible with the response in the RT task. Crucially, the degree of crosstalk was varied by instructing participants either to attend to the left-right orientation of the objects, creating explicit cross-task response-code overlap ("strong crosstalk"), or to attend to object identity (no direct overlap; "weak crosstalk"). The data indicated a relative benefit for cross-task compatible trials, which was much greater with strong crosstalk than with weak crosstalk. Crucially, however, even on compatible trials dual-task performance was substantially worse with strong crosstalk than with weak crosstalk. This overall cost of crosstalk suggests interference of response codes even on compatible dual-task trials.


Precision profiling and components of variability analysis for Affymetrix microarray assays run in a clinical context.
Although gene expression profiling using microarray technology is widely used in research environments, adoption of microarray testing in clinical laboratories is currently limited. In an attempt to determine how such assays would perform in a clinical laboratory, we evaluated the analytical variability of Affymetrix microarray probesets using two generations of human Affymetrix chips (U95Av2 and U133A). The study was designed to mimic potential clinical applications by using multiple operators, machines, and reagent lots, and by performing analyses throughout a period of several months. A mixed model analysis was used to evaluate the relative contributions of multiple factors to overall variability, including operator, instrument, run, cRNA/cDNA synthesis, and changes in reagent lots. Under these conditions, the average probeset coefficient of variation (CV) was relatively low for present probesets on both generations of chips (mean coefficient of variation, 21.9% and 27.2% for U95Av2 and U133A chips, respectively). The largest contribution to overall variation was chip-to-chip (residual) variability, which was responsible for between 40 to 60% of the total variability observed. Changes in individual reagent lots and instrumentation contributed very little to the overall variability. We conclude that the approach demonstrated here could be applied to clinical validation of Affymetrix-based assays and that the analytical precision of this technique is sufficient to answer many biological questions.


A live attenuated DIVA vaccine affords protection against Listeria monocytogenes challenge in sheep.
Listeria monocytogenes (Lm) is a deadly foodborne pathogen that comprises 14 serotypes, among which, serotype 4b Lm is the primary cause of listeriosis outbreaks in humans and animals. Here, we evaluated the safety, immunogenicity, and protective efficacy of a serotype 4b vaccine candidate Lm NTSNΔactA/plcB/orfX in sheep. The infection dynamics, clinical features, and pathological observation verified that the triple genes deletion strain has adequate safety for sheep. Moreover, NTSNΔactA/plcB/orfX significantly stimulated humoral immune response and provided 78% immune protection to sheep against lethal wild-type strain challenge. Notably, the attenuated vaccine candidate could differentiate infected and vaccinated animals (DIVA) via serology determination of the antibody against listeriolysin O (LLO, encoded by hly) and phosphatidylinositol-specific phospholipase C (PI-PLC, encoded by plcB). These data suggest that the serotype 4b vaccine candidate has high efficacy, safety, and DIVA characteristics, and may be used to prevent Lm infection in sheep. Our study provides a theoretical basis for its future application in livestock and poultry breeding.


Protein tyrosine kinases in nervous system development.
Protein tyrosine kinases are important mediators of intracellular signaling during nervous system development. Activation of receptor protein tyrosine kinases by neurotrophic factors are initial events in the development of discrete cell populations. The patterns of expression and characterization of substrates for nonreceptor protein tyrosine kinases indicates that they also play a crucial role in neuronal development. The observed functional redundancy among protein tyrosine kinases and their associated intracellular signaling pathways underscores the need for further characterization of these novel interactions to elucidate the mechanisms regulating nervous system development.


Long-term statin safety and efficacy in secondary prevention: can combination therapy improve outcomes?
The use of statins has been associated with substantial reductions in vascular morbidity and mortality. The Prospective Pravastatin Pooling Project (PPP) looked at the long-term safety and efficacy of statins in secondary prevention, based on pooled results from three key statin trials. PPP revealed a highly significant relative risk reduction in total mortality, and demonstrated that pravastatin has a similar incidence of muscle-related side effects as placebo. It has been speculated that treatment with statins in combination with other cardiovascular drugs may have a synergistic effect on reduction of cardiovascular complications. However, for ethical reasons, evidence can only ever be sought from sub-group analyses or meta-analyses of existing studies. Recent studies have focused on statins plus acetyl- salicylic acid (ASA, aspirin). Evidence suggests that a combination of statins with ASA provides a cardiovascular risk reduction that is superior to the respective monotherapy. Thus, statins effectively reduce further cardiovascular morbidity and mortality as well as total mortality in patients with manifest coronary artery disease (CAD) or at high risk, also they act in synergy with ASA and they are safe.


METTL4 catalyzes m6Am methylation in U2 snRNA to regulate pre-mRNA splicing.
N 6-methylation of 2'-O-methyladenosine (Am) in RNA occurs in eukaryotic cells to generate N6,2'-O-dimethyladenosine (m6Am). Identification of the methyltransferase responsible for m6Am catalysis has accelerated studies on the function of m6Am in RNA processing. While m6Am is generally found in the first transcribed nucleotide of mRNAs, the modification is also found internally within U2 snRNA. However, the writer required for catalyzing internal m6Am formation had remained elusive. By sequencing transcriptome-wide RNA methylation at single-base-resolution, we identified human METTL4 as the writer that directly methylates Am at U2 snRNA position 30 into m6Am. We found that METTL4 localizes to the nucleus and its conserved methyltransferase catalytic site is required for U2 snRNA methylation. By sequencing human cells with overexpressed Mettl4, we determined METTL4's in vivo target RNA motif specificity. In the absence of Mettl4 in human cells, U2 snRNA lacks m6Am thereby affecting a subset of splicing events that exhibit specific features such as 3' splice-site weakness and an increase in exon inclusion. These findings suggest that METTL4 methylation of U2 snRNA regulates splicing of specific pre-mRNA transcripts.


Pregnancies in Gaucher disease: a 5-year study.
The study was undertaken to investigate the outcome of pregnancies in Gaucher disease, particularly in enzyme-treated women. A retrospective study was performed of pregnant women evaluated at a referral clinic. There were 43 (17 treated, 26 untreated) women with 66 pregnancies (23 treated, 43 untreated). The live birth rate was 78.3% among treated, 86.0% among untreated. One treated woman had three spontaneous abortions; 3 untreated women had one each. Four pregnancies in each group had postpartum bleeding, 7 requiring transfusions. Postpartum infections were prevalent among treated. Cesarean sections were generally for historic reasons. There was no exacerbation of Gaucher disease, except one bone crisis. Most untreated women with milder disease enjoyed an uncomplicated course. Enzyme-treated patients (ie, with more severe disease) had more bleeding and infections post partum, but few had spontaneous abortions. Hematologic consultation is recommended. A review of world experience with pregnant patients with Gaucher disease is included.


[Simulator for individual auditory training of hard-of-hearing persons].
A device-trainer intended for individual exercises with patients suffering from an intensively pronounced hearing defect is described. The device permits it to reproduce sound signals amplifying them up to 130 dB in the mono-binaural and also in the stereophonic modes and provides for a wide bandwidth. The originals can be presented by using the auditory and vibro-tactile reception.


The risk of cancer in patients with primary Sjögren syndrome: a single-center study from Turkey.
The aim of this study is to determine the risk of cancer in patients with primary Sjögren syndrome (pSS) from a single center in Turkey. Clinical data of the subjects with pSS were retrospectively analyzed. The incidence of cancer for general population was obtained from GLOBOCAN 2018. Age- and sex-specific standardized incidence ratios (SIR) of solid and hematological cancers were calculated compared with the general population. Four hundred thirty patients with pSS were included in the study. The majority of the patients were female (n = 396, 92.1%), and the mean age was 58.6 ± 12.0 years. Thirty-four patients (7.9 %) were diagnosed with cancer (26 solid and 8 hematological) during follow-up. The SIR for all cancers was 2.45 (95% CI, 1.625-3.275). The SIR was 2.42 (95% CI, 1.542-3.298) for solid cancers and 8.42 (95% CI, 2.394 - 14.446) for hematological cancers. The most diagnosed malignancies were breast cancer (n = 6), ovarian cancer (n = 6), and non-Hodgkin lymphoma (NHL) (n = 4). There was an increased risk for ovarian cancer (SIR 12.76, 95% CI, 2.545-22.975). The SIR values were 2.08 (95% CI, 0.419-3.741) and 10.81 (95% CI, 0.216-21.404) for breast cancer and NHL, respectively. The risk of hematological and solid cancers was higher in the patients with pSS when compared to general population. In our pSS cohort, the risk for ovarian cancer was found to be increased, which has not been previously reported in the literature.


Posttraumatic extracapsular temporomandibular bony ankylosis between the coronoid process and base of the skull. Report of a case.
Extracapsular temporomandibular bony ankylosis between the coronoid process and the base of the skull but not involving the zygomatic arch is very uncommon. We have presented such a case, which developed secondary to heterotopic bone formation following trauma. Treatment consisted of ostectomy between the sigmoid notch and the base of the skull.


Identification by differential display of a chicken tolloid-related metalloprotease specifically expressed in the caudal notochord.
While the ventralizing factor Sonic hedgehog is expressed in the entire notochord (Development 121 (1995) 2537) the latter displays distinct ventralizing activities along its rostrocaudal axis. Hence, in HH stage-10 chicken embryo, the caudal notochord exhibits floor plate inducing capacities lost by rostral regions (Development 117 (1993) 205). Therefore, we hypothesize that the caudal notochord produces some cofactors which may contribute to its ventralizing properties. In order to identify such molecules we applied the differential display strategy and isolated a secreted Tolloid-related metalloprotease displaying a regionalized expression in the notochord.


Attenuation of phenotypical expression of severe hemophilia A in presence of simultaneous prothrombotic Factor V mutation: The debate continues.
The effect of coexistence of the prothrombotic Factor V Leiden mutation on the phenotypical expression in hemophilia is still debatable. Six-year-old boy with severe hemophilia A had presented with large soft tissue hematoma, treated with Factor VIII concentrate. Simultaneous Factor V Leiden mutation had resulted in attenuation of clinical features.


Antibody-mediated regulation of basophils: emerging views and clinical implications.
An increasing number of human diseases, including allergies, infections, inflammation, and cancer, involve roles for basophils. Traditionally viewed as the rarest leukocytes that are present only in the circulation, basophils have recently emerged as important players in systemic as well as tissue-specific immune responses. Their functions are regulated by immunoglobulins (Igs), and this enables basophils to integrate diverse adaptive and innate immunity signals. IgE is well known to regulate basophil responses in the context of type 2 immunity and allergic inflammation; however, growing evidence shows that IgG, IgA, and IgD also shape specific aspects of basophil functions relevant to many human diseases. We discuss recent mechanistic advances underpinning antibody-mediated basophil responses and propose strategies for the treatment of basophil-associated disorders.


Judgments of emotion in words and faces: ERP correlates.
Visual event-related potentials (ERPs) to two types of stimuli (faces and words) were analyzed to determine the effects of the perceived emotional connotations of the stimuli (positive, neutral, or negative) in 10 right-handed normal functioning adult males. Principal component analysis (PCA) of the ERPs reveals 5 factors accounting for over 90% of the ERP waveform variance for both faces and words. In the facial data, two ERP components varied in amplitude according to the perceived emotional connotation of the stimulus. For the P3 component, neutrally rated stimuli produced significantly larger amplitudes than stimuli rated as positive or negative. This effect was lateralized to the left hemisphere. A later positive component, the slow wave (448-616 ms), manifested complementary effects, i.e. faces perceived as positive and negative produced larger amplitudes than those perceived as neutral over the right hemisphere. The verbal stimuli did not result in significant main effects for perceived emotional connotation, but produced subtle connotation-related differences in slow wave topography. Hemispheric asymmetries, unrelated to affective connotation, were evident in the verbal data, manifesting different patterns of lateralization depending on the ERP component. The results suggest that differential processing of emotional connotation affects ERP waveforms and that the effects can be understood in terms of ERP components known to be associated with more general aspects of cognitive processing.


"Sunbursts" and "christiesomes": cellular fragments in normal cow and goat milk.
Goats' milk includes numerous cell fragments ("christiesomes") which originate from the mammary secretory cells, contain well preserved endoplasmic reticulum, mitochondria and lipid droplets, and are responsible for the considerable triglyceride synthesising capacity of fresh goat milk. Cows' milk shows a few such particles only after repeated oxytocin-aided milkings. Cows' milk does contain quite different particles which have a dense content with a few small vesicles and numerous microvillus-like protrusions on one side ("sunbursts"). These have not been found in goats milk. Cytoplasmic particles similar to sunbursts have been found on the surface of the mammary secretory epithelium. It is suggested that they are residues of dead cells.


Social withdrawal in Parkinson's disease: A scoping review.
Parkinson's disease (PD) can interfere with individuals' social functioning and lead to social withdrawal. Social withdrawal may result in negative outcomes for persons with PD and their caregivers, such as decreased quality of life. It is necessary to understand the nature of social withdrawal in PD in order to develop strategies to address this issue and prevent negative outcomes. The purpose of this scoping review was to synthesize existing evidence regarding social withdrawal in PD. We searched PubMed, CINAHL, and PsycINFO for studies of social withdrawal in individuals living with PD. Findings were organized according to study characteristics, measurement and description of social withdrawal, prevalence, associated factors, and interventions. Fifty-eight studies were included. We found that persons with PD reduced social activities voluntarily and involuntarily, and social withdrawal was related to various factors including physical, cognitive, and psychiatric symptoms and perceived stigma. Community-based social activity programs appeared to improve social participation. Few studies employed longitudinal methods or tested interventions to reduce social withdrawal. Social withdrawal is associated with various negative outcomes in PD, though more research is needed to understand the true scope of this problem. Limitations in social withdrawal research include vague conceptualization and methodological limitations (i.e., instrumentation and study design), as well as a paucity of interventional studies. The findings of this review can be used to guide hypothesis generation and future study design, with the ultimate goal of mitigating social withdrawal and improving quality of life for people with PD.


CTX-M-producing Klebsiella spp. in a Brazilian hospital: what has changed in 6 years?
CTX-M-encoding genes from Klebsiella spp. strains isolated in 2000 and 2006 were characterized as well as their genetic environment. CTX-M-2 variants were predominant in Klebsiella pneumoniae strains, which showed a greater variability in bla(CTX-M) genes, integrons, and plasmids in 2006 when compared to strains collected in 2000. CTX-M-9-producing Klebsiella oxytoca was identified in 2000 as clonal dissemination.


Flow cytometry as a method for studying effects of stressors on primary rat neurons.
The mechanisms associated with cell death have been an important focus for neurobiology research. In the present study, the methodology of flow cytometry was used to optimize quantification of the toxic effects of tumor necrosis factor-alpha (TNF-alpha), trans-4-hydroxy-2-nonenal (4-HNE), and aged amyloid-beta (Abeta1-42) on rat primary cortical neurons. The fluorescent dyes annexin V-FITC and propidium iodide (PI) were used to identify populations of viable, early apoptotic, necrotic and late apoptotic cells by flow cytometry. Prior to exposure, the primary cultures showed 83% cell viability. Flow cytometry following labeling of cells with a specific neuronal marker, TUJ-1, revealed 82% pure neuronal populations, whereas approximately 7% were astrocytic as shown by glial fibrillary acidic protein positivity. Exposure of primary cultures to TNF-alpha, 4-HNE, and aged Abeta1-42 gave an increased number of early apoptotic cells. We show that flow cytometry is a suitable method for quantifying effects of different stressors on neurons in primary cultures. This technique could be useful for screening and testing of pharmacological compounds relevant to neurodegenerative disorders.


[A case of racemose hemangioma of the right bronchial artery and intercostal to pulmonary arterial anastomosis].
We reported a case of racemose hemangioma of the bronchial artery and intercostal to pulmonary arterial anastomosis. A 67-year-old woman was admitted because of repeated hemoptysis. Bronchoscopic examination revealed a torous lesion of the right B7 bronchus. Intercostal angiography demonstrated communications between right dilated, meandered intercostal arteries and right pulmonary artery. Bronchial angiography showed dilatation and convolution of the right bronchial artery. Angiographic embolization of the right bronchial artery and the right intercostal artery was underwent. There was no recurrence of hemoptysis one year after the embolization procedure. We think that angiographic embolization is an effective method of treatment of hemoptysis due to racemose hemangioma of the bronchial artery and intercostal to pulmonary arterial anastomosis.


[Surgical management of fractures of the proximal end of the radius].
The problems of dislocated proximal radial fractures are discussed by presentation of 47 cases treated operatively. After operation, 74,6% of these patients had good results with complete elbow function. Special attention is paid to indication and possibilities of operative treatment as well as to intra- and postoperative complications.


Reproductive and teratologic studies with isoflurane.
The volatile anesthetic, Isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether), was investigated at anesthetic concentrations to determine its effects on reproduction in rats treated prior to mating, on fetal development in rats and rabbits when administered during various stages of gestation, and on fetal survival in rats treated during late pregnancy. No adverse reproductive effects were observed, and no evidence of teratogenic activity was obtained. Fetal survival was low in rats exposed during late pregnancy but whether or not this finding is related to Isoflurane exposure requires confirmation.


Insulin as an adiposity signal.
Insulin is now well established as an adiposity signal that acts in the brain to influence energy homeostasis. It is secreted in direct proportion to adiposity; it enters the brain from the blood, and it interacts with neurons in the ventral hypothalamus. Experimental manipulation of brain insulin causes predictable changes of food intake and body weight. Because insulin shares many properties with other adiposity signals, especially leptin, in this regard, it is important to recognize the similarities and differences in the signal each conveys to the brain in order to design effective therapeutic approaches to treat pathologies of eating and body weight.