A weighted information criterion for multiple minor components and its adaptive extraction algorithms.
Minor component (MC) plays an important role in signal processing and data analysis, so it is a valuable work to develop MC extraction algorithms. Based on the concepts of weighted subspace and optimum theory, a weighted information criterion is proposed for searching the optimum solution of a linear neural network. This information criterion exhibits a unique global minimum attained if and only if the state matrix is composed of the desired MCs of an autocorrelation matrix of an input signal. By using gradient ascent method and recursive least square (RLS) method, two algorithms are developed for multiple MCs extraction. The global convergences of the proposed algorithms are also analyzed by the Lyapunov method. The proposed algorithms can extract the multiple MCs in parallel and has advantage in dealing with high dimension matrices. Since the weighted matrix does not require an accurate value, it facilitates the system design of the proposed algorithms for practical applications. The speed and computation advantages of the proposed algorithms are verified through simulations.


Carotido-brachial artery bypass for radiation induced injury of the subclavian artery. The value of a lateral mid-arm approach.
Symptomatic subclavian artery damage, following radiation for breast or head and neck cancer, is very rare. We report three new cases in which arterial insufficiency of the upper limb developed respectively 3, 36, and 27 years after irradiation for breast cancer in two cases and tumor of the clavicle in one case. Patients were treated by saphenous vein by-pass using a new extra-anatomic route from the carotid to the brachial artery. They were two main differences from the classical carotido-brachial by-pass. The brachial artery was approached by a lateral mid-arm incision between the biceps and the humeral bone, and the grafts were tunnelled, subcutaneously, laterally on the medial head of the deltoid muscle avoiding the hump of the clavicle, and then between the biceps and the humeral bone. The postoperative courses were uneventful with good healing of the wounds. All grafts remained long-term patent and no compression was detected by ultrasound and arteriogram. This new technique of extra-anatomic carotido-brachial by-pass is a safe and efficient alternative to treat radiation induced injury of the subclavian artery.


[Shock - Review for Clinicians].
Diagnosing and managing patients in shock is a challenge for the treating clinicians in acute medicine. Early diagnosis and treatment are crucial. Mortality of septic shock is between 40 % and 60 %, and that of the cardiogenic shock about 40 %. This article provides an overview of diagnostic approaches to the patient in shock, different aetiologies and treatment strategies, and it guides the clinician through the management from first contact until definite treatment.


A pharmacopsychometric overview of major depressive episodes in positive psychiatry.
ABSTRACTBackground:The use of the pharmacopsychometric triangle to enhance patient-reported well-being as the ultimate goal of treatment has most intensively been studied in patients with a major depressive episode. The review is structured on the pharmacopsychometric triangle in which the desired clinical effect of an antidepressive medication is balanced against the undesired side effects induced by this medication in terms of restored well-being. As a biological treatment, the antidepressive medication is compared clinically with both electroconvulsive therapy and psychological treatment. In the process of this review, evidence from a dose-response study in patients suffering from a major depressive episode with an adequate duration and symptom severity has demonstrated that the dose-response relationship emerged when using the patient-reported well-being outcome rather than the symptomatic reduction as outcome. The pharmacopsychometric triangle is in patients with major depressive episodes providing important information within positive psychiatry.


Loss of in vitro resistance in Candida glabrata following discontinuation of fluconazole prophylaxis in a hematopoietic stem cell transplantation patient.
We report a case of fluconazole-resistant oropharyngeal colonization caused by a strain of Candida glabrata that rapidly regained susceptibility once prophylaxis with this agent was discontinued and echinocandin therapy was initiated. Isolates collected before and after discontinuation of fluconazole were confirmed to be isogenic by RAPD analysis. Transcription analysis demonstrated constitutive expression of genes encoding efflux pumps in the isolate recovered on fluconazole prophylaxis and transient expression in those isolates collected after fluconazole was discontinued.


Potential protective effect of catechin on doxorubicin-induced cardiotoxicity in adult male albino rats.
Doxorubicin (DOX) is the most effective and frequently used anticancer drug but its cardiotoxicity is the most important side effect that limits the clinical use of it. This study was designed to investigate the protective role of catechin (CAT) on DOX induced cardiotoxicity. Rats were randomly divided into three groups. Group (I) served as the control. Group (II) served as toxic group, (1.66 mg/kg; i.p.). Group (III) served as protective group, was pretreated with (400 mg CAT/kg; p.o.) for 2 weeks then received DOX with CAT for 12 days. In the present study, administration of DOX induced significant (p < 0.001) reductions in cardiac tissue level of reduced glutathione (GSH) and activities of antioxidant enzymes (catalase, superoxide dismutase (SOD), and glutathione-S- transferase (GST)). Moreover, it resulted in a significant (p < 0.001) increase in cardiac tissue concentrations of nitric oxide (NO), H2O2 and malondialdehyde (MDA) as well as serum levels of cardiac injury biomarkers (lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB)) which were reversed by treatment with CAT. DOX administration induced the loss of myofibrils, hemorrhage, and congested blood vessels. Ultrastructural results revealed loss of myofibrils and intercalated disks and mitochondrial degeneration. All histopathological alterations were reversed by the treatment with CAT. Catechin, as an antioxidant, showed protective effects against DOX cardiotoxicity via reducing lipid peroxidation, inflammation, and alleviating apoptosis.


[Expression of embryonal and differentiational proteins in chordomas and in the notochord].
The expression of the embryonal and of the differentiational proteins in 12 cases of chordoma and in the notochord of a 4-month-old and a 5-month-old human embryo have been examined immunohistologically by the ABC method using polyclonal antibodies to CEA, AFP, or S-100, and the monoclonal antibody to cytokeratin. It was found that S-100 was expressed in all cases of chordoma and in the notochords examined. CEA and cytokeratin also were found expressed in some cases of chordoma but not in the notochords. These proteins were found expressed more strongly in chordomas without a metastasis than in those with a metastasis. In the metastatic lesions, these proteins were expressed more strongly than in the primary lesions. The antibody to AFP reacted with neither the chordomas nor the notochords tested. These results suggest a possible link between the gene-expression of the tumor cells and the microenvironment in which they are harbored.


Economic growth, CO2 emissions, renewable waste and FDI relation in Pakistan: New evidences from 3SLS.
First attempt has been made to find the effects of foreign direct investment on environmental pollution and economic growth, in addition to finding the determinants of foreign direct investment inflows in Pakistan using the annual data set for the period of 1980-2014. Simultaneous equation model has been used to find relation between the variables of concern. Results from technique and composition effects show that increase in economic growth leads towards more pollution emissions. Scale effect shows stock of capital and labor have positive effect on the economic growth of Pakistan while pollution has negative effect on growth. In case of capital accumulation effect, economic growth and foreign direct investment have positive and significant effect on stock of capital. Although increase in economic growth increases pollution, however, economic growth declines as pollution crosses a certain limit. Foreign direct investment is also found positively related with pollution.


Temperature determination using Kalpha spectra from M -shell Ti ions.
The compact multipulse terawatt (COMET) laser facility at LLNL was used to irradiate Al-coated 2-50 microm Ti foils with approximately 10(19) W cm(-2) , 500 fs, 3-6 J laser pulses. Laser-plasma interactions on the front side of the target generate hot electrons with sufficient energy to excite inner-shell electrons in Ti, creating Kalpha emission which has been measured using a focusing spectrometer with spatial resolution aimed at the back surface of the targets. The spatial extent of the emission varies with target thickness. The high spectral resolution (lambda/Deltalambda approximately equal to 3800) is sufficient to measure broadening of the Kalpha emission feature due to the emergence of blueshifted satellites from ionized Ti in a heated region of the target. A self-consistent-field model is used to spectroscopically diagnose thermal electron temperatures up to 40 eV in the strongly coupled Ti plasmas.


Scalp basal cell carcinoma: A different entity?
Basal cell carcinoma is the most frequent malignant neoplasm in white-skinned individuals. It develops in different body areas, including in the scalp, which is a unique anatomical region due to the high number of pilosebaceous follicles; the scalp is protected from UV exposure, a main risk factor for basal cell carcinoma development. Moreover, scalp basal cell carcinoma has been described as more aggressive and difficult to treat than other forms of basal cell carcinoma. In this study, we reviewed the clinical and pathological characteristics, risk factors, genetics, and treatment options for scalp basal cell carcinoma to better understand this special type of cancer. Even though it is not yet clear whether scalp basal cell carcinomas represent a different entity, it seems important to give them special attention due to their potential aggressiveness, invasion capacities, tendency to relapse, and treatment difficulties.


[Adult intramedullary gliomas].
Intramedullary gliomas are rare tumors accounting for less than 4% of all primary central nervous system tumors. The aims of this retrospective multicenter study were to assess their natural outcome as well as management. We studied 332 patients from 1984 to 2011. Histopathological examination revealed 72% ependymomas (94% were low grade tumors), 24% astrocytomas (29% were high grade tumors), 2.4% mixed gliomas and 1.7% oligodendrogliomas. The mean age at diagnosis was 42.4 years for ependymomas, with male predominance, versus 39.6 years for astrocytomas. Pain was the most common initial presentation. In 20% of cases, astrocytomas were biopsied alone, but more than 80% of ependymomas had surgical resection. Radiotherapy and chemotherapy were reserved for malignant tumors, especially if they were ependymomas. The 5-year survival rate was 76.8% for astrocytomas and 94.5% for ependymomas. Histology, functional status prior to surgery, and tumor grade are among the prognostic factors. Our study showed that surgical treatment of gliomas is well codified, at least for ependymomas, but adjuvant treatment continues to play a marginal role in the management even in astrocytomas, which are infiltrative tumors.


The role of monocyte cytotoxic factor in monocyte-mediated lysis of tumour cells.
The role of a monocyte cytotoxic factor (CF) in monocyte-mediated lysis of leukaemia cells (K562) has been investigated using a polyclonal rabbit antiserum raised against purified CF. The CF antiserum inhibited K562 cell lysis mediated by interferon gamma (IFN-gamma)-activated monocytes. CF antiserum also inhibited monocyte-mediated lysis of antibody-coated K562 cells (AbK562). Preimmune serum at the same concentration as CF antiserum did not affect monocyte-mediated lysis, and the CF antiserum did not inhibit binding between effector and target cells, indicating that inhibition of monocyte-mediated lysis by CF antiserum was not merely a result of toxic components present in the rabbit serum, or a result of a decrease in monocyte-target cell binding. Taken together, the data suggest that CF is involved in monocyte-mediated lysis of uncoated as well as antibody-coated K562 cells.


The Klebsiella pneumoniae O2a antigen defines a second mechanism for O antigen ATP-binding cassette transporters.
An ATP-binding cassette (ABC) transporter-dependent mechanism is responsible for the biosynthesis of polysaccharide O antigens in the lipopolysaccharides of many Gram-negative bacteria. In the Escherichia coli O9a prototype, addition of a non-reducing terminal modification regulates chain length. The terminal residue is an export signal recognized by the nucleotide-binding domain component of the cognate ABC transporter. The Klebsiella pneumoniae O2a antigen lacks a capping residue, and the corresponding nucleotide-binding protein does not contain a separate substrate-binding domain. Unlike the O9a transporter, the O2a transporter can export heterologous O antigens. Export of the O2a antigen is obligatorily coupled to chain elongation, and the O2a transporter is essential for establishing O antigen chain length. The E. coli O9a transporter operates after chain length has been determined. Furthermore biosynthesis and export can be uncoupled. O antigen chain length is a critical element in the ability of lipopolysaccharides to confer resistance to complement-mediated killing. This study establishes that two distinctly different approaches are available for the regulation of O antigen chain length and export via an ABC transporter.


Associations of albumin and nutritional index factors with delirium in patients admitted to the cardiac intensive care unit.
Limited data are available on the association of malnutrition with the occurrence of delirium in the cardiac intensive care unit (CICU). Thus, we aimed to analyze whether nutritional indices and their components can predict the development of delirium in CICU. We enrolled 2,783 patients admitted to the CICU of Samsung Medical Center for more than 24 h between September 2012 and December 2018. We assessed the nutritional status at admission using three indices, the Prognostic Nutrition Index (PNI), the Geriatric Nutritional Risk Index (GNRI), and the Controlling Nutritional Status (CONUT). Then, we compared predictive performances for the occurrence of delirium among nutritional indices using Delong's test. Delirium developed in 678 patients (24.3%) assessed three times daily for 7 days of CICU stay. Nutritional indices had fair predictive performance for development of delirium in critically ill cardiac patients using the area under the receiver-operating characteristic curve (AUROC: 0.729 for the GNRI, 0.728 for PNI, and 0.762 for CONUT). Furthermore, the AUROC of albumin alone (0.77, 95% CI, 0.75-0.79) was significantly greater than that of either GNRI (p < 0.001) or PNI (p < 0.001). In a multivariable analysis including each component of nutritional indices, albumin was a significant predictor for delirium but not absolute lymphocyte count, bodyweight/ideal bodyweight, or total cholesterol level as a component of nutritional indices. Predictive performances of nutritional indices for the occurrence of delirium were acceptable in patients admitted to CICU. Albumin alone might be a helpful and straightforward indicator for the occurrence of delirium.


The "left-hand rule" in directional changes of the needle holder with different needle grips. Suturing technique in a restricted operating space.
While using a needle for suturing in a restricted operating space, surgeons change the direction of the needle holder by modifying needle grips. Such directional changes, however, have not been analyzed systematically. The "left-hand rule", similar to Fleming's rule in physics, is proposed as a guide in comprehending these changes. When the thumb is assumed to represent the direction of the holder in the standard grip, the long axis of the index finger represents that of a grip in which the needle is held obliquely [oblique (Ob) grip]. In the usual (tip-ward) Ob grip with ordinary suturing (advancing the needle by supination), the holder is shifted in the direction opposite to the fingertip (towards the arm) and, in that with reversed suturing (by pronation), towards it. The middle finger represents a grip in which the needle is held after rotation [rotated (Ro) grip]. In the usual (counter-clockwise) Ro grip, the holder is shifted in the direction opposite to the fingertip (towards the back of the hand) in both ordinary and reversed suturing.


Horner's syndrome as a complication of thyroidectomy: report of a case.
We report a case of Horner's syndrome (HS) occurring as a complication after total thyroidectomy. Horner's syndrome is characterized by myosis, eyelid ptosis, enophthalmos, and lack of sweating, with vascular dilatation of the lateral part of the face, caused by damage of the cervical sympathetic chain. We found only 28 other reports of HS developing after thyroidectomy, and only seven of these patients recovered completely. Of the 495 thyroidectomies performed at our hospital between 1997 and 2007, only one (0.2%) was complicated by the development of HS. The patient was a 35-year-old woman who underwent total thyroidectomy for Basedow-Graves' disease. Horner's syndrome manifested on postoperative day 2, but without anhydrosis or vascular dilatation of the face, and the symptoms resolved spontaneously 3 days later. The possible causes of HS after thyroidectomy include postoperative hematoma, ischemia-induced neural damage, and stretching of the cervical sympathetic chain by the retractor. The prompt and complete recovery of this patient suggests that the cervical sympathetic chain was damaged by retractor stretching.


Child sexual abuse: its impact and treatment.
Sexual victimization of children is a relatively new area of enquiry and initial studies have been directed towards identification and etiology. It is only recently that treatment issues are beginning to be addressed. This paper first reviews the literature on the direct and indirect effects of sexual abuse on the child victim, and outlines five key issues in treatment. The major foci in treatment to date are described and a number of existing models, which have been devised to address these treatment issues, are briefly summarized.


The nature of short-term consolidation in visual working memory.
Short-term consolidation is the process by which stable working memory representations are created. This process is fundamental to cognition yet poorly understood. The present work examines short-term consolidation using a Bayesian hierarchical model of visual working memory recall to determine the underlying processes at work. Our results show that consolidation functions largely through changing the proportion of memory items successfully maintained until test. Although there was some evidence that consolidation affects representational precision, this change was modest and could not account for the bulk of the consolidation effect on memory performance. The time course of the consolidation function and selective influence of consolidation on specific serial positions strongly indicates that short-term consolidation induces an attentional blink. The blink leads to deficits in memory for the immediately following item when time pressure is introduced. Temporal distinctiveness accounts of the consolidation process are tested and ruled out. (PsycINFO Database Record


A multifunctional ultra-thin acoustic membrane with self-healing properties for adaptive low-frequency noise control.
This paper proposes a novel multifunctional ultra-thin membrane based on a Polyborosiloxane-based gel with stimuli-responsive sound absorption and sound transmission loss (STL) and characterised by excellent self-healing properties. This adaptive behaviour is the result of a dynamically activated phase transition in the membrane's polymeric network which is given by the interaction with the travelling sound pressure wave. The presence and the extent of such phase transition in the material was investigated via oscillatory rheological measurements showing the possibility to control the dynamic response by modifying the Boron content within the polymer. Acoustic analyses conducted at different stimuli responses showed high and dynamic absorption (95%) at the absorption coefficient peaks and an adaptive shift to lower frequencies while sound amplitudes were increased. An average STL up to 27 dB in the frequency range between 500 to 1000 Hz was observed and an increased STL above 2 dB was measured as the excitation amplitude was increased. Results demonstrated that the new membrane can be used to develop deep subwavelength absorbers with unique properties (1/54 wavelength in absorption and 1/618 in STL) able to tune their performance in response to an external stimulus while autonomously regaining their properties in case of damage thanks to their self-healing ability.


Sociotropy-autonomy and interpersonal problems.
Sociotropy and autonomy are conceptualized as two personality dimensions that relate to an individual's vulnerability to depression. Sociotropy is characterized as an excessive investment in interpersonal relationships, and autonomy is characterized as an excessive concern with personal achievement and control. This study examined the relationships between sociotropy and autonomy, and a variety of interpersonal problems with close and nonclose others. Results suggested that sociotropic individuals are overly nurturant to nonclose others but vindictive to individuals who are close to them. In contrast, autonomous individuals were found to be domineering to nonclose others but socially avoidant toward people close to them. These findings are discussed in the context of recent research regarding the interpersonal patterns associated with sociotropy and autonomy.


Recent trends in feline intestinal neoplasia: an epidemiologic study of 1,129 cases in the veterinary medical database from 1964 to 2004.
A retrospective epidemiologic study evaluated 1,129 feline intestinal tumor patients via data entered into the Veterinary Medical Database (VMDB) from 1964 to 2004. Cases were analyzed by breed, age, yr of diagnosis, tumor type, and location. The VMDB incidence of all intestinal tumors reported during this 40 yr period was 0.4%, with small intestinal tumors predominating. The most common intestinal tumor was lymphoma, but the most common nonlymphoid tumor was adenocarcinoma. The Siamese breed and increasing age after 7 yr conferred an increased risk. Intact males and females appeared to have a decreased risk compared with neutered patients, but this may be explained by the age difference among these patients as older patients were more likely to be neutered. Prospective studies evaluating neuter status predilection and prognosis are warranted.


Ophthalmic, ultrasonographic findings in primary central nervous system lymphoma with ocular involvement.
To describe and classify ophthalmic, ultrasonographic findings in patients with primary central nervous system lymphoma with ocular involvement. B- and A-scan ultrasonography was performed on the eyes of 13 patients with primary central nervous system lymphoma with ocular involvement. In seven patients, the eyes were the site of initial involvement. In the other six patients, both ocular and central nervous system disease were present at the initial evaluation. All patients had abnormal ultrasonographic findings. The most common were vitreous debris (n = 10), choroidal-scleral thickening (n = 6), and widening of the optic nerve (n = 4). Elevated chorioretinal lesions (n = 3) and retinal detachment (n = 2) were also found. Ophthalmic ultrasonography is a useful adjunctive diagnostic technique for characterizing ocular involvement in lymphoma. Ocular lymphoma may present as chorioretinitis, vitreitis and nonspecific uveitis; it produces characteristic, but nonspecific findings on ultrasonography. The diagnosis of ocular involvement is an important factor in determining treatment.


Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial.
High-frequency left-sided repetitive transcranial magnetic stimulation (HFL-TMS) has been shown to have antidepressant effects in double-blind trials. Low-frequency stimulation to the right prefrontal cortex (LFR-TMS) has also shown promise, although it has not been assessed in treatment-resistant depression and its effects have not been compared with those of HFL-TMS. To prospectively evaluate the efficacy of HFL-TMS and LFR-TMS in treatment-resistant depression and compared with a sham-treated control group. A double-blind, randomized, sham-controlled trial. Two general psychiatric services. Sixty patients with treatment-resistant depression who had failed to respond to therapy with multiple antidepressant medications were divided into 3 groups of 20 that did not differ in age, sex, or any clinical variables. All patients completed the double-blind phase of the study. Twenty 5-second HFL-TMS trains at 10 Hz and five 60-second LFR-TMS trains at 1 Hz were applied daily. Sham stimulation was applied with the coil angled at 45 degrees from the scalp, resting on the side of one wing of the coil. Main Outcome Measure Score on the Montgomery-Asberg Depression Rating Scale. There was a significant difference in response among the 3 groups (F56,2 = 6.2), with a significant difference between the HFL-TMS and sham groups and between the LFR-TMS and sham groups (P<.005 for all) but not between the 2 treatment groups. Baseline psychomotor agitation predicted successful response to treatment. Both HFL-TMS and LFR-TMS have treatment efficacy in patients with medication-resistant major depression. Treatment for at least 4 weeks is necessary for clinically meaningful benefits to be achieved. Treatment with LFR-TMS may prove to be an appropriate initial repetitive TMS strategy in depression taking into account safety, tolerability, and efficacy considerations.


Study on the necessity for cross-section imaging of the posterior mandible for treatment planning of standard cases in implant dentistry.
To investigate whether cross-section imaging influences the planning and therapy of standard implant cases in the posterior mandible. In a prospective study conducted over 16 months, the planned treatment (standard implant therapy without bone augmentation procedures in the premolar and molar regions of the mandible) was compared with the postoperative result in 50 randomly selected patients. Clinical examinations and panoramic radiographs were performed pre- and postoperatively, whereas cross-sectional tomography was performed only preoperatively. The vertical magnification factor in the panoramic radiographs was very constant pre- and postoperatively with 1 : 1.27 and in the spiral tomograms with 1 : 1.52. In 11 of 77 implant sites, the mandibular canal could not be evaluated in the spiral tomograms. The additional information from cross-sectional spiral tomography did not influence the original planning in 74 of 77 (96.1%) implant sites. Based on the postoperative panoramic radiograph, the average distance from the tip of the implants to the mandibular canal was 3.04+/-2.06 mm. In two cases (2.6%), transient postoperative altered tactile sensation of the mental nerve was found. The information from preoperative cross-sectional spiral tomography has minor impact on treatment planning in standard implant cases in mandibular premolar and molar regions. The clinical examination provides sufficient information for selecting implant diameter and the panoramic radiograph provides sufficient information for implant length selection.


Tissue penetration and antimicrobial activity of standard- and high-dose trimethoprim/sulfamethoxazole and linezolid in patients with diabetic foot infection.
The purpose of this study was to conduct a pharmacokinetic and pharmacodynamic evaluation of high (320/1600 mg) and standard (160/800 mg) doses of trimethoprim/sulfamethoxazole and linezolid in outpatients with mild diabetic foot infections (DFIs). Both viable skin/soft tissue from the infection site and serum were obtained at various times after antibiotic administration from 18 patients (6 per study group) being treated with linezolid, standard doses of trimethoprim/sulfamethoxazole or high doses of trimethoprim/sulfamethoxazole during a follow-up clinic visit. These samples were assayed for drug concentrations by liquid chromatography in tandem with mass spectrometry. Patient sera were also utilized in time-kill assays against two strains of Staphylococcus aureus and three strains of β-haemolytic streptococci. The mean tissue/serum ratio for linezolid was 0.46 (range, 0.18-0.71). The mean tissue/serum ratio for trimethoprim was 1.2 (range, 0.3-4.5) for both standard and high doses, and 0.23 (range, 0.1-0.46) and 0.36 (range, 0.14-1.28) for standard and high doses of sulfamethoxazole, respectively. Linezolid exhibited inhibitory activity in time-kill assays against strains of S. aureus (0.45 ± 0.5 log10 cfu/mL) and β-haemolytic streptococci (2.2 ± 0.6 log10 cfu/mL), while trimethoprim/sulfamethoxazole exhibited bactericidal (>3 log kill) activity against all of these isolates. These findings were consistent for each sampling time and for high as well as standard doses of trimethoprim/sulfamethoxazole. This pharmacokinetic/pharmacodynamic study found that trimethoprim/sulfamethoxazole exhibits good skin/soft tissue penetration in patients with DFIs as well as bactericidal activity in serum against strains of S. aureus and β-haemolytic streptococci.


Effect of microwaves (2450-MHz) on the immune system in mice: studies of nucleic acid and protein synthesis.
CBA/J adult male mice were given single or triple exposures to 2450-mHz microwaves in an environmentally controlled wave guide facility. The average absorbed dose rate for a single exposure varied from 12 to 15 mW/g. Sham-exposed mice served as controls. Lymphoid cells were collected and tested for metabolic activity on days 3, 6, and 9 following a single exposure, and on days 9, 12, and 16 following triple exposures on days 0, 3, and 6. Cells were cultured in vitro for four hours to seven days before their metabolic rates were assayed. Under these conditions, microwaves failed to produce any detectable change in deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein synthesis, as measured by the incorporation of methyl(3H)-thymidine (3H-TDR) (DNA substrate), 3H-uridine (3H-UR) (RNA substrate), and 3H-leucine (protein substrate) by spleen, bone marrow, and peripheral blood lymphocytes (PBL) in vitro. These data suggest that microwave-induced increases in the frequency of complement-receptor (CR)- or surface-immunoglobulin (sIg)-bearing cells were not associated with a concomitant increase in cell proliferation and/or protein synthesis, and favor the concept that microwaves under these conditions stimulate already existing B-cell precursors for maturation.


Health insurance and access to care among Social Security Disability Insurance beneficiaries during the Medicare waiting period.
For most Social Security Disability Insurance (SSDI) beneficiaries, Medicare entitlement begins 24 months after the date of SSDI entitlement. Many may experience poor access to health care during the 24-month waiting period because of a lack of insurance. National Health Interview Survey data for the period 1994-1996 were linked to Social Security and Medicare administrative records to examine health insurance status and access to care during the Medicare waiting period. Twenty-six percent of SSDI beneficiaries reported having no health insurance, with the uninsured reporting many more problems with access to care than insured individuals. Access to health insurance is especially important for people during the waiting period because of their low incomes, poor health, and weak ties to the workforce.


[Gonarthrosis: physiokinesitherapy treatment].
After a description of the main features of gonarthrosis, the physiokinesitherapy techniques employed in the treatment of this joint condition are presented. This is followed by remarks on hospital cases encountered.


Effects of practice of serial tests of attention in healthy subjects.
The effects of practice on the serial performance of auditory and visual attention tasks were investigated in 10 healthy volunteers tested at 2 to 4 weekly intervals over eight test sessions using a battery of psychometric tests. Subjects as a group showed an ability to significantly (p = .05) improve their performances over time on all tests except for the Simple Reaction Time and Symbol Digit Modalities Test, the latter demonstrating a trend towards improvement (p = .07). Improvement when it occurred was almost uniformly linear and on tests such as the Pegboard and Stroop, was still discernable at the eighth session. On tests such as Paced Visual Serial Addition Task, floor effects were noted after five sessions and no further improvement was possible. In general, younger subjects tended to make fewer errors, perform quicker and improve for longer periods than their older counterparts. The results indicate that on tests of attention, healthy subjects have the ability to significantly improve performance with practice and this may extend over as many as eight discrete test sessions. The implications for neuropsychological research are discussed.


Deep Learning Classification of Spinal Osteoporotic Compression Fractures on Radiographs using an Adaptation of the Genant Semiquantitative Criteria.
Osteoporosis affects 9% of individuals over 50 in the United States and 200 million women globally. Spinal osteoporotic compression fractures (OCFs), an osteoporosis biomarker, are often incidental and under-reported. Accurate automated opportunistic OCF screening can increase the diagnosis rate and ensure adequate treatment. We aimed to develop a deep learning classifier for OCFs, a critical component of our future automated opportunistic screening tool. The dataset from the Osteoporotic Fractures in Men Study comprised 4461 subjects and 15,524 spine radiographs. This dataset was split by subject: 76.5% training, 8.5% validation, and 15% testing. From the radiographs, 100,409 vertebral bodies were extracted, each assigned one of two labels adapted from the Genant semiquantitative system: moderate to severe fracture vs. normal/trace/mild fracture. GoogLeNet, a deep learning model, was trained to classify the vertebral bodies. The classification threshold on the predicted probability of OCF outputted by GoogLeNet was set to prioritize the positive predictive value (PPV) while balancing it with the sensitivity. Vertebral bodies with the top 0.75% predicted probabilities were classified as moderate to severe fracture. Our model yielded a sensitivity of 59.8%, a PPV of 91.2%, and an F1 score of 0.72. The areas under the receiver operating characteristic curve (AUC-ROC) and the precision-recall curve were 0.99 and 0.82, respectively. Our model classified vertebral bodies with an AUC-ROC of 0.99, providing a critical component for our future automated opportunistic screening tool. This could lead to earlier detection and treatment of OCFs.


Comparative genomic analysis of azasugar biosynthesis.
Azasugars are monosaccharide analogs in which the ring oxygen is replaced with a nitrogen atom. These well-known glycosidase inhibitors are of interest as therapeutics, yet several aspects of azasugars remain unknown including their distribution, structural diversity, and chemical ecology. The hallmark signature of bacterial azasugar biosynthesis is a three gene cluster (3GC) coding for aminotransferase, phosphatase, and dehydrogenase enzymes. Using the bioinformatics platform Enzyme Similarity Tool (EST), we identified hundreds of putative three gene clusters coding for azasugar production in microbial species. In the course of this work, we also report a consensus sequence for the aminotransferase involved in azasugar biosynthesis as being: SGNXFRXXXFPNXXXXXXXLXVPXPYCXRC. Most clusters are found in Bacillus and Streptomyces species which typically inhabit soil and the rhizosphere, but some clusters are found with diverse species representation such as Photorhabdus and Xenorhabdus which are symbiotic with entomopathogenic nematodes; the human skin commensal Cutibacterium acnes, and the marine Bacillus rugosus SPB7, a symbiont to the sea sponge Spongia officinalis. This pan-taxonomic survey of the azasugar 3GC signature may lead to the identification of new azasugar producers, facilitate studies of their natural functions, and lead to new potential therapeutics.


Dispersion polymerization of methyl acrylate in nonpolar solvent stabilized by block copolymers formed in situ via the RAFT process.
The free-radical dispersion polymerization of methyl acrylate (MA) in isododecane was carried out in the presence of a poly(2-ethylhexyl acrylate) macromolecular RAFT (reversible addition-fragmentation chain transfer) agent bearing a trithiocarbonate reactive group in the middle of the chain (P2EHA-TTC). The presence of the trithiocarbonate function was crucial for the synthesis of monodisperse colloidal poly(methyl acrylate) (PMA) particles stabilized by the P2EHA segments. The hydrodynamic diameters ranged from 100 to 300 nm, using particularly low amounts of the macro(RAFT agent) (1-6 wt % vs. MA) in dispersion polymerizations carried out at 20 wt % solids content. As shown by 2D liquid chromatography, P2EHA-b-PMA or P2EHA-b-PMA-b-P2EHA block copolymers formed in situ at the early stage of the dispersion polymerization due to the reversible transfer process and played the role of particle stabilizer. The glass-transition temperature of the derived polymer films was not affected by the low amount of the chosen macromolecular stabilizer and the mechanical properties were mainly those of PMA, which makes the technique very attractive for coating applications.


Discovery of LNP1892: A Precision Calcimimetic for the Treatment of Secondary Hyperparathyroidism.
The calcium sensing receptor (CaSR) plays an important role in maintaining calcium homeostasis. The use of calcimimetic cinacalcet has been established to activate CaSR and normalize hypercalcemia. However, cinacalcet has limitations due to its high cLogP and pKa. A systematic optimization of cinacalcet to reduce its cLogP and pKa yielded compound 23a (LNP1892). Compound 23a showed excellent potency and a favorable pharmacokinetics profile, and lacked the liabilities of cinacalcet, making it a highly differentiated precision calcimimetic. In adenine-diet-induced chronic kidney disease (CKD) models, 23a demonstrated robust and dose-dependent efficacy, as measured by plasma parathyroid hormone (PTH) levels. It also showed an excellent safety profile in animal studies. Phase 1 clinical trials with 23a in healthy volunteers confirmed its excellent safety, tolerability, and effectiveness in lowering PTH levels in a dose-dependent manner, without causing symptomatic hypocalcaemia. Encouraged by these promising results, LNP1892 was taken to a Phase 2 study in CKD patients.


MALDI: more than peptide mass fingerprints.
Over the past decade, matrix-assisted laser desorption/ionization (MALDI) has developed from a phenomenon that was interesting only to physicists and mass spectrometrists, and has evolved into a widespread applied ionization technique in chemistry, biology and biomedicine. The introduction of MALDI offers all the advantages of mass spectrometry (MS) for the analysis of large biomolecules. Proteins, carbohydrates and oligonucleotides have been analyzed with MS-inherent accuracy, sensitivity, resolution and speed. In addition to electrospray ionization-MS, MALDI-MS has a great impact on the challenges of the post-genome area. The recent status of MALDI application in proteomics, biomolecular interaction analysis-MS and carbohydrate analysis, in addition to single nucleotide polymorphism genotyping is reviewed.


A new system for cutting brain tissue preserving vessels: water jet cutting.
The water jet cutting system allows transaction and dissection of biological structures with little bleeding. Structures of higher tissue rigidity remain unchanged while softer tissues are mechanically dissected. In brain tissue, all vessels larger than 20 microns are left intact after the passage of the jet stream with a pressure of up to 5 bar, and therefore vessels can be isolated selectively from the surrounding tissue. Oedema is present adjacent to the cut and no increase of temperature occurs.


Evaluation of a novel delayed-type hypersensitivity assay to Candida albicans in adult and neonatal rats.
Delayed-type hypersensitivity (DTH) is a T-cell-mediated immune response that may be used for immunotoxicity testing in non-clinical species. However, in some cases DTH assays using T-dependent antigens may be confounded by the production of antibodies to the antigen. The authors have previously modified a DTH assay, initially validated in the mouse, for use in juvenile rats to assess the effect of immunosuppressive drugs on the developing rat immune system. The assay measures footpad swelling induced by subcutaneous footpad injection of Candida albicans (C. albicans) derived-chitosan in rats previously sensitized with C. albicans. Antibodies to chitosan are not produced in this model. However, considerable inter-animal variability inherent in the footpad swelling assay can make it difficult to precisely quantify the magnitude of the immune response and inhibition by immunosuppressants, particularly if complete suppression is not observed. This report describes the development of an ex vivo assay to assess DTH in rats using interferon (IFN)-γ production by splenocytes, obtained from rats sensitized with C. albicans, as the quantifiable measure of the DTH response. Adult and neonatal rats administered dexamethasone (DEX), a known immunosuppressant, exhibited immunosuppression as evidenced by a reduction in ex vivo IFNγ production from splenocytes challenged with C. albicans-derived chitosan. Current data indicate that the ex vivo based DTH assay is more sensitive than the conventional footpad swelling assay due to a lower background response and the ability to detect a response as early as post-natal day (PND) 12. The ex vivo based rat DTH assay offers a highly sensitive and quantitative alternative to the footpad swelling assay for the assessment of the immunotoxic potential of drugs. The increased sensitivity of the ex vivo DTH assay may be useful for identifying smaller changes in response to immunotoxic drugs, as well as detecting responses earlier in animal development.


Medicine and Charity in Eighteenth-century Northumberland: The Early Years of the Bamburgh Castle Dispensary and Surgery, c. 1772-1802.
In 1772 in Bamburgh Castle, Northumberland, a charitable institution was established by Dr John Sharp to offer medical provision to the poor of the parish, which was remote from the Newcastle and Edinburgh Infirmaries. Unlike urban institutions, which have dominated hospital historiography, the Bamburgh dispensary was small, occupying only a few rooms in the castle, and situated in a remote, coastal location. And yet, at its height, the Bamburgh dispensary treated thousands of patients per year, often exceeding dispensaries in large towns, and was equipped with the latest medical technologies. Unlike the majority of infirmaries and dispensaries it was not funded by subscription, nor run by governors, but was entirely funded by the Lord Crewe Trust, and administered by Dr Sharp. While Bamburgh is certainly an anomaly, it raises new questions about voluntary institutional medical provision for rural populations, and forms of medical philanthropy.


Necrotizing vasculitis with granulomatosis.
Table 1 summarizes some of the differentiating characteristics among these diseases. Clinically, the differentiating features are that classic Wegener's granulomatosis involves both the upper and lower respiratory systems and kidneys. Renal involvement is the major cause of morbidity and mortality. Churg-Strauss syndrome has the distinguishing characteristics of an allergic asthmatic prodrome and a profound eosinophilia. It encompasses and destroy's tissue not only of the lungs but also most of the other organ systems in the body. A major cause of mortality is cardiac disease, which is not a feature of either of the other two diseases. Finally, lymphomatoid granulomatosis is seen predominantly in the lungs, skin, and central nervous system and is the only one of the three that is associated with the development of a lymphoma. Although there are definitive clinical differences of these entities, as mentioned above, it is the histopathologic features that can diagnostically separate the three. Wegener's granulomatosis is predominantly a necrotizing granulomatous infiltrate that has a polymorphous infiltrate of neutrophils, plasma cells, and histiocytes and is very distinct from the eosinophilic granulomas of CSS or the lymphocytic ones of LYG. Finally, all of the diseases respond differently to medications. Patients with Churg-Strauss syndrome for the most part respond well to high dosages of oral steroids and usually do not require therapy with immunosuppressive agents. Therapy with steroids alone is not adequate for the treatment of Wegener's granulomatosis, and the therapy is a combination of steroids with chemotherapeutic agents, cyclophosphamide being the agent of choice. The most difficult disease to treat in this review is LYG.(ABSTRACT TRUNCATED AT 250 WORDS)


Glucose-regulated proinsulin processing in isolated islets from rat pancreas.
We demonstrated previously that the conversion rate of proinsulin to insulin in pancreatic islets progressively increased after prolonged prior exposure to glucose (11 mM) and that this effect could be blocked by cycloheximide. This study was designed to characterize further the time course and regulation of the proinsulin conversion process. The effects of prior exposure to glucose on proinsulin conversion were dose dependent (Km, approximately 7 mM glucose) and time dependent, taking approximately 3 h to reach the maximum rate. Glucose added at or after the subsequent [3H]leucine pulse was ineffective. Mannoheptulose, added during a 3-h exposure with glucose (11 mM), prevented glucose-induced activation of the proinsulin conversion process. L-Leucine (20 mM) was as effective as 11 mM glucose in activating conversion, whereas 2-alpha-ketoisocaproic acid (20 mM) or phorbol ester (50 nM) had little effect. Activation of proinsulin conversion by a 24-h exposure to glucose (11 mM) was reversed by a subsequent 3-h prior exposure to cycloheximide. alpha-Amanitin, an inhibitor of mRNA synthesis, did not influence the glucose-induced activation of proinsulin conversion when present during a 3-h exposure to glucose; however, it completely inhibited glucose-stimulated conversion when present during 24 h exposure. Results suggest that activation of the proinsulin conversion process is regulated by glucose metabolism rather than the glucose molecule per se and that other, but not all, secretagogues are effective. Conversion may require prior synthesis of a pool of converting enzyme(s) or other regulatory proteins whose turnover is relatively rapid (approximately 33 h) and whose mRNA is more stable (to 24 h).


[Liver biopsy in surgery of the gallbladder].
Biopsy of the liver with the menghini needle was done as a routine diagnostic procedure during surgery in 581 cases. During earlier decades morphological changes of the liver could be demonstrated by that procedure in 80-100% of the patients. In contrast such changes could be found only in 55% of our cases; in 5,5% these changes were severe. From these numbers it should be concluded that liver biopsy during gall bladder surgery is not necessary as a routine procedure. If patients are selected for biopsy on the basis of history, ultrasonography, laboratory data and intraoperative microscopical liver findings this procedure is necessary only in 14% of the cases, complication rate being 0,09%. In this particularly selected group changes of the liver can be found in 90,4%, severe changes in 33% of the cases. Pathological changes of the liver are likely to occur in 65-91% of patients with complicated gall stone disease and/or accompanying diseases like diabetes, obesitas, alcoholism, or a history of hepatitis. In this particular group biopsy and histological examination during surgery seem to be indicated as it was the case before.


[Developmental dyslexia and dysgraphia--a case report].
We reported a 7-year-old, right-handed boy whose reading and writing of kana and kanji were impaired. He also showed a severe deficit in visuo-spatial perception skills. Nevertheless, his ability to read and write kana characters was facilitated by means of the Japanese Syllabaries. It is generally considered that the Syllabary involve two kinds of language modalities: auditory-verbal and visuo-verbal language systems. In spite of his intact auditory-verbal language system, his visuo-verbal language skills involved in writing kanji were severely impaired. It was suggested that a severe deficit of visuo-spatial perception skills influenced performance of visuo-verbal language systems. Accordingly, we inferred that the patient recalled a kana character by use of the Japanese Syllabaries based on his good auditory-verbal language system, and supposed that his reading and writing disorders were similar to alexia with agraphia in adult patients with angular lesions.


Mitochondrial genome of the hydrothermal vent shrimp Nautilocaris saintlaurentae (Crustacea: Caridea: Alvinocarididae).
We determined the mitochondrial genome (mitogenome) of Nautilocaris saintlaurentae, sampled at vent fields of the Tofua Arc in the southwestern Pacific. The genome was 15,928 bp in length and had the typical mitogenome structure of the infraorder Caridea. Its protein-coding genes were very similar to other alvinocaridid species in respect to length, AT content, and start and stop codons. However, N. saintlaurentae showed a 17.4--19.2% divergence in the nucleotide sequence from other alvinocaridid species. This information will be helpful in understanding the genetic relationship among members of the alvinocaridid shrimps.


Functional assesment of patients with AIDS disease.
We documented the types and degree of functional disability in 74 patients with AIDS at the Hospital de Clínicas of the Federal University of Paraná, Brazil. Few of these patients are referred for rehabilitation services and there is only a limited team approach in their care. We found that 91% of the patients had some degree of functional impairment; in 81% the complaint was weakness and in 47% it was neurological involvement. According to the Barthel Index, 79% were considered functionally independent, 14% partially dependent and 7% dependent. For most of them, independence requires effort and their quality of life is reduced. Severe disability was rather unusual, while mild or moderate disability levels were not. The functional physical disability found in 21% of the patients required management by a rehabilitation team. We conclude that it is important to focus attention on the quality of life of patients with AIDS.


Anti-inflammatory and anti-tumor-promoting effects of 5-deprenyllupulonol C and other compounds from Hop (Humulus lupulus L.).
A new phloroglucinol derivative, 5-deprenyllupulonol C (1), along with four other phloroglucinol derivatives, 2-5, five chalcones, 6-10, four flavanones, 11-14, two flavonol glycosides, 15 and 16, and five triterpenoids, 17-21, were isolated from the female inflorescence pellet extracts of hop (Humulus lupulus L.). Upon evaluation of these compounds against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells, twelve compounds, i.e., 1-4, 11-14, 17-19, and 21, showed potent inhibitory effects on EBV-EA induction, with IC₅₀ values in the range of 215-393 mol ratio/32 pmol TPA. In addition, eleven compounds, i.e., 1-4, 6, 11, 12, 14, 17, 18, and 20, were found to inhibit TPA-induced inflammation (1 μg/ear) in mice, with ID₅₀ values in the range of 0.13-1.06 μmol per ear. Further, lupulone C (2) and 6-prenylnaringenin (14) exhibited inhibitory effects on skin-tumor promotion in an in vivo two-stage mouse-skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and with TPA as promoter.


Vulnerable families: a study of health visitors' prioritization of their work.
Changes in the NHS have supported the idea of targeting health services to those in greatest need. This has meant that health visitors are increasingly having to identify 'vulnerable' families in need of increased health visiting intervention. This paper reports on a qualitative study undertaken in order to explore the ways in which health visitors plan and organize their work in relation to the concept of vulnerability. Focus groups and semi-structured interviews were carried out with health visitors from two separate geographical areas, one an inner city area and the other suburban, in order to explore the criteria by which health visitors define vulnerability and decide to increase their levels of intervention to particular families. It was found that vulnerability was extremely difficult to define but that the health visitors used criteria which were appropriate to the particular localities in which they worked to identify vulnerable families and to increase their levels of intervention to those families. Health visitors were targeting their services within a framework of a basic minimum service to all and were assessing the health needs of individuals or families rather than planning their work on the basis of community or practice profiles.


Human neutrophils express low levels of FcγRIIIA, which plays a role in PMN activation.
We have identified a rare healthy FcγRIIIB (CD16B)-null donor completely lacking FCGR3B RNA and protein expression and dissected the role of the different neutrophil Fcγ receptors in the response to therapeutic anti-CD20 monoclonal antibodies. We observed that polymorphonuclear neutrophils (PMNs) from FcγRIIIB wild-type (WT) individuals or the null donor were more effectively activated by chronic lymphocytic leukemia (CLL) B-cell targets opsonized with glycoengineered anti-CD20 antibodies compared with fully core-fucosylated anti-CD20 antibodies, suggesting the presence and role of FcγRIIIA (CD16A) on PMNs. Indeed, we demonstrated by reverse-transcription polymerase chain reaction, flow cytometry, and western blot analysis that PMNs from FcγRIIIB WT donors and the null individual express low levels of FcγRIIIA on their surfaces. FcγRIIIA is a functional and activating molecule on these cells, because anti-CD16 F(ab')2 antibodies alone were able to activate highly purified PMNs from the FcγRIIIB-null donor. Use of blocking anti-CD16 and anti-CD32 antibodies showed that FcγRIIIA is also a major mediator of phagocytosis of CD20-opsonized beads by FcγRIIIB WT and null PMNs. In contrast, trogocytosis of antibody-opsonized CLL B cells by PMNs was mediated primarily by FcγRIIIB in WT PMNs and by FcγRIIA in null PMNs. We conclude that FcγRIIIA is an important player in PMN functions, whereas FcγRIIIB is dispensable for activation and phagocytosis. We discuss the clinical implications of these findings.


Prospective validation of stringent dose constraints for prostatic stereotactic radiation monotherapy: results of a single-arm phase II toxicity-oriented trial.
There are no safety-focused trials on stereotactic body radiotherapy (SBRT) for localized prostate cancer. This prospective 3‑year phase II trial used binomial law to validate the safety and efficacy of SBRT with stringent organ at risk dose constraints that nevertheless permitted high planning target volume doses. All consecutive ≥ 70-year-old patients with localized prostate adenocarcinoma who underwent SBRT between 2014 and 2018 at the National Radiotherapy Center in Luxembourg were included. Patients with low Cancer of Prostate Risk Assessment (CAPRA) scores (0-2) and intermediate scores (3-5) received 36.25 Gy. High-risk (6-10) patients received 37.5 Gy. Radiation was delivered in 5 fractions over 9 days with Cyberknife-M6™ (Accuray, Sunnyvale, CA, USA). Primary study outcome was Common Terminology Criteria for Adverse Events version 4 (CTCAEv4) genitourinary and rectal toxicity scores at last follow-up. Based on binomial law, SRBT was considered safe in this cohort of 110 patients if there were ≤ 2 severe toxicity (CTCAEv4 grade ≥ 3) cases. Secondary outcomes were biochemical progression-free survival (bPFS) and patient quality of life (QOL), as determined by the IPPS and the Urinary Incontinence QOL questionnaire. The first 110 patients who were accrued in a total cohort of 150 patients were included in this study and had a median follow-up of 36 months. Acute grade ≥ 3 toxicity never occurred. One transient late grade 3 case was observed. Thus, our SBRT program had an estimated severe toxicity rate of < 5% and was safe at the p < 0.05 level. Overall bPFS was 90%. QOL did not change relative to baseline. The trial validated our SBRT regimen since it was both safe and effective.


Design of transfections: Implementation of design of experiments for cell transfection fine tuning.
Transfection is the process by which nucleic acids are introduced into eukaryotic cells. This is fundamental in basic research for studying gene function and modulation of gene expression as well as for many bioprocesses in the manufacturing of clinical-grade recombinant biologics from cells. Transfection efficiency is a critical parameter to increase biologics' productivity; the right protocol has to be identified to ensure high transfection efficiency and therefore high product yield. Design of experiments (DoE) is a mathematical method that has become a key tool in bioprocess development. Based on the DoE method, we developed an operational flow that we called "Design of Transfections" (DoT) for specific transfection modeling and identification of the optimal transfection conditions. As a proof of principle, we applied the DoT workflow to optimize a cell transfection chemical protocol for neural progenitors, using polyethyleneimine (PEI). We simultaneously varied key influencing factors, namely concentration and type of PEI, DNA concentration, and cell density. The transfection efficiency was measured by fluorescence imaging followed by automatic counting of the green fluorescent transfected cells. Taking advantage of the DoT workflow, we developed a new simple, efficient, and economically advantageous PEI transfection protocol through which we were able to obtain a transfection efficiency of 34%.


Coordination-Induced Radical Generation: Selective Hydrogen Atom Abstraction via Controlled Ti-C σ-Bond Homolysis.
A method for the generation of transient alkyl radicals via homolytic Ti-C bond cleavage was developed by employing a tailor-made organotitanium half-cage complex. In contrast to established metal-mediated radical initiation protocols via thermal or photochemical M-C σ-bond homolysis, radical formation is triggered solely by coordination of a solvent molecule (thf) to a titanium(IV) center. During the reaction, the nonstabilized alkyl radical is formed along with a persistent titanium(III) metalloradical, thus taming the former transient radical (persistent radical effect). Radical coupling and hydrogen atom abstraction (HAT) reactions have been explored not only experimentally but also computationally and by means of kinetic analysis. Exploiting these findings led to the development of selective HAT transformations, for example, with 9,10-dihydroanthracene. Deuterium labeling studies using selectively deuterated alkyls and 9,10-dihydroanthracene-d4 confirmed a radical pathway, which was underpinned by developing a radical-radical cross-coupling reaction for transferring the alkyl radical to a stable Sn-centered radical. To set the stage for an application in organic synthesis, a 5-endo-trig radical cyclization based on our methodology was established, and a dihydroxylated sesquiterpene was thus prepared in high diastereomeric excess.


Endoscopic decontamination: an audit and practical review.
A comprehensive audit of endoscopic decontamination practices throughout a 1200-bedded teaching hospital trust was undertaken, prior to a review of the current policy and consideration of alternative disinfectants. Pharmacy records of glutaraldehyde usage, occupational health staff survey data of glutaraldehyde exposure, discussions with all departments where endoscopy might be conducted and information from all companies supplying endoscopes and allied equipment were reviewed. In total, 56 endoscopes were found to be in use in 16 areas of the Trust. In the main designated endoscopy units, compliance with the established policy was generally good, but in other areas, equipment which could tolerate autoclaving was being disinfected with chemical sterilants; some units were still using endoscopes which were not fully immersible and there was widespread use of disinfectant troughs, rather than automated washer-disinfectors. In most cases, this was because staff were concerned about endoscopy equipment passing to a central processing department with potential delays and losses. An updated Trust-wide endoscopy policy, using glutaraldehyde and incorporating the current British Thoracic Society, British Gastroenterological Society and British Urological Society guidelines, has now been implemented. The issues around this and alternative disinfectants are discussed.


Antemortem diagnosis of hepatic adenocarcinoma in a ewe.
A 4-year-old ewe with weight loss, anorexia, and high liver enzyme activities was diagnosed at necropsy as having cholangiocellular carcinoma that had metastasized to kidneys, adrenal glands, heart, lungs, mediastinum, and peritoneal surface of the diaphragm. Cholangiocellular carcinoma is an uncommon neoplasm of sheep. Evaluation of liver tissue obtained via ultrasound-guided percutaneous liver biopsy had suggested an antemortem diagnosis of adenocarcinoma of the liver.


Depressive symptoms are associated with reduced neutrophil function in hip fracture patients.
Hip fracture is a common trauma in older adults with a high incidence of depression, which relates to poorer prognosis including increased risk of infection. Ageing is accompanied by reduced immunity, termed immunesenescence, resulting in increased susceptibility to infection. We examined whether physical trauma (hip fracture) and psychological distress (depressive symptoms) had additive effects upon the aged immune system that might contribute to poor outcomes after injury. Neutrophil function was assessed in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and 43 healthy age-matched controls (28 female). Thirty eight fracture patients had depressive symptoms at 6 weeks. No difference in neutrophil phagocytosis of Escherichia coli was observed between controls and hip fracture patients, but superoxide production was significantly reduced in hip fracture patients with depressive symptoms compared with patients without symptoms (p=.001) or controls (p=.004) at 6 weeks. Superoxide production improved 6 months following fracture to the level seen in controls. We detected elevated serum cortisol, reduced dehydroepiandrosterone sulphate (DHEAS) and an increased cortisol:DHEAS ratio in fracture patients with depressive symptoms compared with patients without depressive symptoms or controls at 6 weeks and 6 months after injury. Serum IL6, TNFα and IL10 were higher among patients with depressive symptoms at 6 weeks. The cortisol:DHEAS ratio and IL6 levels related to depressive symptom scores but not to neutrophil function. In conclusion, depressive symptoms related to poorer neutrophil function after hip fracture, but this was not driven by changes in stress hormone or cytokine levels.


Development of validated quantitative structure-retention relationship models for retention indices of plant essential oils.
Quantitative structure-retention relationship (QSRR) models were developed for the retention indices of 505 frequently reported components of plant essential oils. Multiple linear regression was used to build QSRR models for the dimethyl silicone, dimethyl silicone with 5% phenyl groups, and polyethylene glycol stationary phases. We tried to improve the variable selection and modeling method based on prediction method for selecting the optimum descriptors from the molecular weight, 75 topological indices, and 170 atom-type E-state indices. The three-variable QSRR models perform high correlation coefficients of 0.937 for dimethyl silicone and 0.933 for dimethyl silicone with 5% phenyl groups stationary phase. Four variables were selected to developed QSRR model for the polyethylene glycol stationary phase. The leave-one-out and leave-many-out cross-validations, bootstrapping, and y-randomization test showed the three models are robust and have no chance correlation. The external validation with the test set showed the three models present high externally predictive power. The three models presented high-quality fit, internally, and externally predictive power. It is expected that the models can effectively predict retention indices of essential oils components without experimental value.


The association between Dietary Diversity Score and odds of nonalcoholic fatty liver disease: a case-control study.
There is no previous study that investigated the association between Dietary Diversity Score (DSS) and odds of nonalcoholic fatty liver disease (NAFLD). The present study aimed to examine the association between DDS and its components and NAFLD among Iranian adults. In the case-control study, we enrolled 121 newly diagnosed cases of NAFLD and 122 with age, BMI and sex-matched controls. All NAFLD patients were diagnosed through ultrasonography methods by gastroenterologists. Anthropometric parameters of participants including weight, height, hip circumference and waist circumference were measured. A validated 147-item semi-quantitative food frequency questionnaire was applied to assess the usual dietary intakes of participants. Binary logistic regression was conducted to estimate the risk of NAFLD in relation to DDS and its components, including refined grains, vegetables, fruits, dairy and meats. The mean age of study participants was 42.7 years of them 53.1% were male. Higher adherence to DDS [odds ratio (OR) = 0.48; 95% confidence interval (CI), 0.25-0.95] and vegetable group (OR = 0.34; 95% CI, 0.16-0.71) were remarkably associated with lower risk of NAFLD, after adjusting for several confounders including age, BMI, physical activity, energy intake, job, education, and antihypertensive drugs usage. Contrastingly, greater adherence to the refined grain (OR = 3.36; 95% CI, 1.44-7.87) and meat group (OR = 3.27; 95% CI, 1.25-6.90) was significantly associated with increased risk of NAFLD. High DDS is inversely correlated with the risk of NAFLD. Hence, increasing the diversity score of diet by emphasizing the higher diversity scores for vegetables and less for meat and refined grains may be profitable for the management of NAFLD.


Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development.
Although T cell dysfunction and lymphopenia are key features of immunodeficient patients with the Wiskott-Aldrich syndrome and Wiskott-Aldrich syndrome protein (WASP)-deficient mice, T cell development appears relatively normal. We hypothesized that N-WASP, a ubiquitously expressed homologue of WASP, may serve a redundant function with WASP. To examine the unique and redundant activities of WASP and N-WASP, we generated ES cells devoid of WASP and N-WASP [double knockout (DKO)] and used the RAG-2-deficient blastocyst complementation system to generate DKO lymphocytes. Moreover, we mated WASP KO mice with mice containing a conditionally targeted N-WASP allele and used the Cre-loxP system to generate mice lacking WASP and N-WASP in T cells [conditional DKO (cDKO)]. In both systems, N-WASP-deficient cells were indistinguishable from WT cells. In contrast, T cell development in DKO and cDKO mice was markedly altered, as shown by thymic hypocellularity and reduced numbers of peripheral T cells. We found that the combined activity of WASP and N-WASP was important for CD4(-)CD8(-) double-negative (DN)-to-CD4(+)CD8(+) double-positive (DP) cell transition, and this may be partly explained by reduced cycling DN3 cells. In addition, decreased migratory responses of CD4(+)CD8(-) and CD4(-)CD8(+) single-positive (SP) cells and increased percentage of CD69(low)CD24(low) and CD62L(low) SP cells in cDKO cells imply retention of SP cells in the thymus. In summary, this study suggests that, although WASP serves a unique role for peripheral T cell function, T cell development depends on the combined activity of WASP and N-WASP.


Glutathione S-transferases of female A/J mouse lung and their induction by anticarcinogenic organosulfides from garlic.
Glutathione S-transferases (GSTs) of female A/J mouse lung have been purified and characterized for their (a) structural interrelationships, (b) substrate specificities toward the ultimate carcinogenic metabolite of benzo(a)pyrene (BP), (+)-anti-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene [(+)-anti-BPDE], and (c) induction by three naturally occurring organosulfides (OSCs)-from garlic [diallyl sulfide (DAS), diallyl trisulfide (DATS) and dipropyl sulfide (DPS)], which significantly differ in their efficacy against BP-induced lung cancer in mice. The GST activity in the lung was due to two alpha class (pI 9.4 and 6.0), two mu class (pI 8.7 and 8.6), and one pi class (pI 8.9) isoenzyme. The GST isoenzyme profile of the lung was different from that of the A/J mouse forestomach, which also is a target organ for BP-induced cancer in mice. Noticeably, an alpha class heterodimeric isoenzyme (pI 9.5) present in the forestomach of A/J mouse, which is exceptionally efficient in the glutathione (GSH) conjugation of (+)-anti-BPDE [X. Hu, S.K. Srivastava, H. Xia, Y. C. Awasthi, and S. V. Singh (1996) J. Biol. Chem. 271, 32684-32688], could not be detected in the lung. The specific activities of the lung GSTs in the GSH conjugation of (+)-anti-BPDE were in the order of GST 8.9 > GST 8.7 > GST 9.4 > GST 6.0. While DPS treatment did not increase the levels of any pulmonary GST isoenzyme, the expression of pi class GST 8.9 was significantly increased in response to both DAS and DATS administrations. Interestingly, DATS, an OSC which lacks activity against BP-induced lung cancer in mice, was a relatively more potent inducer of pi class GST isoenzyme than DAS, which is a potent inhibitor of BP-induced lung tumorigenesis. The results of the present study suggest that a mechanism(s) other than GST induction is likely to be responsible for the differential effects of DAS and DATS on BP-induced lung cancer in mice. Our results also suggest that relatively lower efficacies of the OSCs against BP-induced lung cancer than against forestomach neoplasia may be attributed to (a) a lack of expression in the lung of an isoenzyme corresponding to forestomach GST 9.5 and (b) a comparatively lower level of induction of pi type GST in the lung than in the forestomach by these OSCs.


Influence of treatments in the quality of Nile tilapia (Oreochromis niloticus) fillets.
In this study, the influence of different treatments was evaluated: nonwashing, washing in chlorinated water and washing/soaking in chlorinated water and sodium chloride on the quality of Nile tilapia (Oreochromis niloticus) fillets during storage at 1.0 ± 0.5°C through daily analysis of pH, moisture, and lipids content. Microbiological analysis and growth modeling for mesophilic and psychrotrophic bacteria and Staphylococcus sp. were also carried out. Finally, we confirmed the microbiological safety through sensory analyses. The main results suggest that fillets washed or soaked in chlorinated water and sodium chloride present clear and narrower blood line coloration; that is, they are less oxidized than those that received other treatments and are microbiologically safe for use within 12 days of storage. It was concluded that the treatments in chlorinated and salinized water favored the quality maintenance of fillets.


Maternal IgG avidity, IgM and ultrasound abnormalities: combined method to detect congenital cytomegalovirus infection with sequelae.
We used maternal immunoglobulin M (IgM), immunoglobulin G (IgG) avidity index (AI) and fetal ultrasonography (US) to effectively detect a congenital cytomegalovirus-infected fetus that would suffer neurological sequelae after birth. The detecting method was prospectively adapted to 1163 unselected pregnant women. IgM, IgG and IgG-AI were measured at the first prenatal examination (10.8±2.2 weeks of gestation). Advanced US was performed for the IgM-positive women at our center. The urine of 1163 neonates was examined via PCR. All infected neonates were followed for neurological development. Most women (83.3%) were seropositive. Among them, 40 (4.1%) were IgM positive. Nine of forty (22.5%) had low AI, of which one showed abnormal US and suffered severe sequelae. The remaining eight had a normal US; however, one infant had hearing impairment. There were another three infected infants with normal development. Their mothers' serological results were: IgM positive with high AI (n=1); IgG positive; IgM negative with high AI (n=1); and both IgG and IgM negative (n=1). This method enabled us to detect infected fetuses having severe sequelae. However, the problem remains of detecting infected fetuses that only have a hearing impairment.


Necrotizing Ulcer After BCG Vaccination in a Girl With Leukocyte-adhesion Deficiency Type 1.
Leukocyte-adhesion deficiency-1 is a recessively inherited disorder associated with recurrent bacterial infections, severe periodontitis, peripheral leukocytosis, and impaired wound healing. We diagnosed moderate-type leukocyte-adhesion deficiency-1 in a 7-year-old girl who developed a necrotizing ulcer after Bacillus Calmette-Guerin vaccination. The patient showed moderate expression of CD18 in neutrophils with a homozygous splice mutation with c.41_c.58+2dup20 of ITGB2 and experienced recurrent severe infections complicated with systemic lupus erythematosus. She received hematopoietic stem cell transplantation from a matched elder brother with heterozygous mutation of ITGB2, and has since remained free of infection and systemic lupus erythematosus symptoms without immunosuppression therapy.


Artificial blastocyst collapse prior to vitrification significantly improves Na+/K+-ATPase-dependent post-warming blastocoel re-expansion kinetics without inducing endoplasmic reticulum stress gene expression in the mouse.
Blastocoel expansion during embryo development is known to be reliant on the Na+/K+-ATPase pump, but little is known about the relative contribution of active (Na+/K+-ATPase pump) and facilitated diffusion (aquaporins) water transport during blastocoel re-expansion after vitrification. The aims of this study were to examine potential effects of artificial blastocoel collapse (ABC) on markers of embryo stress and the contribution of active and facilitated diffusion water transport mechanisms to blastocoel re-expansion. Day 5 mouse embryos were vitrified using either a standard protocol, laser pulse ABC, a hyperosmotic sucrose ABC protocol or both laser pulse and sucrose. Using real-time polymerase chain reaction, no differences were found in the gene expression of the endoplasmic reticulum (ER) stress markers activating transcription factor 4 (Atf4) or heat shock protein 90-alpha (Hsp90α) 2h after warming. Similarly, expression of the Na+/K+-ATPase pump gene, ATPase, Na+/K+ transporting, beta 1 polypeptide (Atp1b1) and protein did not differ between groups. Aquaporin 8 (Aqp8) gene expression was significantly lower in the laser+sucrose ABC group than in fresh controls, and aquaporin 3 (Aqp3) expression significantly higher in standard vitrified embryos compared with all other groups. Ouabain, a potent and specific Na+/K+-ATPase pump inhibitor, inhibited blastocoel re-expansion in both standard protocol- and laser ABC-vitrified embryos, reducing both groups to the same rate of re-expansion 3h after warming. These results demonstrate that ABC before vitrification does not alter mRNA or protein expression of Na+/K+-ATPase, or mRNA levels of ER stress genes Atf4 and Hsp90α. Activity of the pump may be increased in ABC embryos, with potential compensation by AQP3 when it is compromised.


Condylar Hyperplasia in a Monozygotic Twin Girl: An Argument About Etiology.
The diagnosis of unilateral condylar hyperplasia (UCH) requires a combined assessment consisting of clinical, radiological, and histopathological examination. The etiology of this condition is unknown. The purpose of this study is to report a rare case of UCH in a monozygotic twin. A 15-year-old girl was referred to our department complaining of facial asymmetry and malocclusion. Computed tomography and single-photon emission computed tomography imaging reveal enlargement of the left condyle and condylar neck, and an increased uptake that was diagnosed as active UCH. During the investigation of family and co-twin facial profile, no cases of UCH were identified. From the case reported in this study, the authors raise a hypothesis that can exist some environmental factor that is related in the development of condylar hyperplasia given the occurrence of this disease in one of twins.


Anti-receptor antibodies designed to elicit "internal image"-bearing anti-idiotypes: a possible AIDS vaccine.
Two obstacles hinder the development of an AIDS vaccine: (1) the AIDS virus exhibits extensive amino acid heterogeneity between isolates and (2) antibodies elicited by virus during the course of natural infection are often non-neutralizing. A vaccine designed to induce anti-idiotypic antibodies against the virus' receptor on T-cells, T4, should, in principle, overcome these obstacles. Such antibody could contain an "internal image" of T4 and bind the receptor binding domain of the virus. Since this domain is both critical to function and, therefore, poorly susceptible to antigenic variation, anti-receptor anti-idiotypic antibodies may demonstrate broad, strain-independent crossreactivity and block viral adherence.


Nature or nurture in low back pain? Results of a systematic review of studies based on twin samples.
Twin studies are becoming popular to investigate risk factors for low back pain (LBP) because they consider the genetic factor and allow for more precise estimates of risks. We aimed to identify and summarize the results of studies based on twin samples investigating risk factors for LBP. The MEDLINE, CINAHL, LILACS, Web of Science and EMBASE databases were searched. Prospective and cross-sectional observational studies of LBP involving twins were included. The exposure factors could be genetics (heritability) or environmental such as smoking, alcohol consumption, body mass index and medical history. Pooling was attempted using an inverse variance weighting and fixed effects model. Twenty-seven studies were included. Estimates of heritability effects ranged from 21% to 67%. The genetic component was higher for more chronic and disabling LBP than acute and less disabling LBP. Smoking was significantly associated with LBP [pooled odds ratio (OR) = 3.0; 95% confidence interval (CI) 2.8-3.3] with a longitudinal and a cross-sectional study also identifying a dose-response relationship in people with chronic LBP. Obesity was associated with LBP (pooled OR = 1.9; 95% CI 1.6-2.2) with a cross-sectional study identifying a dose-response relationship. No association between alcohol consumption and LBP was identified. Co-morbidities such as asthma, diabetes and osteoarthritis were associated with LBP (pooled OR ranging from 1.6 to 4.2). The contribution of genetics to LBP appears to be dependent on the severity of the condition. Twin studies could be better used to explore possible causation paths between lifestyle factors, co-morbidities and LBP.


Randomized trial of Alemtuzumab for prevention of graft rejection and preservation of renal function after kidney transplantation.
A randomized, multicenter, controlled trial was undertaken to evaluate the safety and efficacy of Alemtuzumab, a powerful lytic agent for both T and B lymphocytes, in the prophylaxis of rejection in renal transplantation (RTx). Thirty patients were randomized to receive Alemtuzumab together with low-dose cyclosporine (CsA) monotherapy (CAMPATH, n = 20) or to full doses of CsA with azathioprine and corticosteroids (Standard, n = 10). CsA was administered at doses to achieve whole-blood trough CsA levels of 90 to 110 ng/mL and 180 to 225 ng/mL in CAMPATH and Standard groups, respectively. Per protocol, CsA trough levels were lower in patients assigned to CAMPATH post-RTx (median trough level of 119 vs. 166 ng/mL at 6 months, CAMPATH vs. Standard; 95% confidence interval, -92 to -34). At 6 months post-RTx, serum creatinine, graft and patient survivals, incidence of biopsy proven acute rejection (25% vs. 20%, CAMPATH vs. Standard), overall treatment failure, and severe and moderate infections were comparable. Whereas all patients receiving Standard therapy required maintenance corticosteroids at 6 months, of the 17 of 20 patients with functioning grafts in CAMPATH, 15 (88%, 95% confidence interval, 53%-97%) were steroid free. These results suggest that Alemtuzumab is an effective induction agent that permits low-dose steroid-free immunosuppression in RTx.


The Hydroalcoholic Extract of Leaves of Mandevilla moricandiana Induces NO-Mediated Vascular Relaxation.
Natural products extracted from plants represent a valuable source of new bioactive substances. Many studies describe the potential of plant products for the treatment of cardiovascular diseases. Species of the Mandevilla genus have been studied for their biological activities, mainly as antioxidant, anti-inflammatory, and vasorelaxant. However, the phytochemical and pharmacological profiles of Mandevilla moricandiana have not been investigated yet. The aim of this study was to evaluate the vasodilator effect of the hydroalcoholic extract of the leaves of M. moricandiana, as well as its chemical profile. Chemical analysis and quantification of major compounds were performed by HPLC analysis. Total flavonoid content was quantified based on rutin equivalents, and major compounds were identified based on HPLC-DAD-MS analysis. M. moricandiana leaf extract-induced vasodilation was investigated in rat aortic rings precontracted with phenylephrine. The total flavonoids were quantified as 3.25 ± 0.11 % w/w of the hydroalcoholic leaf extract, and HPLC-DAD-MS allowed for the identification of luteolin and quercetin glycosides. The maximal relaxant effect of the hydroalcoholic leaf extract was 86.07 ± 1.68 % at a concentration of 30 µg/mL (p < 0.05; n = 6). The concentration of hydroalcoholic extract of the leaves of M. moricandiana necessary to reduce phenylephrine-induced contractions of the endothelium-intact aorta by 50 % was 0.82 ± 0.10 µg/mL. M. moricandiana leaf extract-induced vasodilation was abolished in aortas pretreated with NG-nitro-L-arginine methyl ester and 1H-[1,2,4]oxadiazolo-[4,3-α]quinoxalin-1-one. In addition, diphenhydramine partially inhibited the effect of the hydroalcoholic extract of the leaves of M. moricandiana. Thus, M. moricandiana-induced relaxation depends on the endothelium and on the activation of the nitric oxide/cyclic GMP pathway, with the involvement of endothelial histamine H1 receptors. Luteolin and quercetin glycosides seem to contribute to the extract activity.


Are enterally fed ICU patients meeting clinical practice guidelines?
The 2003 Canadian clinical practice guidelines (CPGs) for nutrition support in mechanically ventilated, critically ill patients recommended early EN and maintaining a 45-degree head-of-bed (HOB) angle during EN administration. Current practices at University Health Network have not been examined with regard to these guidelines. The purpose of this study was to determine the proportion of mechanically ventilated, enterally fed intensive care unit patients meeting the CPG recommendations for early EN and HOB elevation. This was a cross-sectional study involving data collection in 2 parts. Early EN data were collected via chart review and HOB data through observation of HOB angle reader. Reasons for not meeting each recommendation were obtained when data were collected via chart review and feedback from nurses. data analysis was conducted using frequency distributions. sixty-six percent of patients met the recommendation for early en. of those not meeting this recommendation, the most common reason for the delay was hemodynamic instability (28.1%). for the hob recommendation, 4.9% of patients met the 45 degree recommendation, and 52.5% had an hob angle between 21 and 30 degrees. the most common reason for not attaining the 45-degree angle was reported as unknown (29.5%). The proportion of patients meeting clinical practice guidelines compares favorably to similar studies. In some cases, patients' clinical conditions or unit HOB angle protocol explained not meeting guidelines. However, there were cases where reasons for not meeting guidelines were unknown.


The human microbiome: from symbiosis to pathogenesis.
The human microbiota is a complex assemblage of the microbes inhabiting many sites in the human body. Recent advances in technology have enabled deep sequencing and analysis of the members and structures of these communities. Two sites, the vagina and gastrointestinal tract, are highlighted to exemplify how technological advances have enhanced our knowledge of the host-microbiota system. These examples represent low- and high-complexity communities, respectively. In each example, certain community structures are identified that can be extrapolated to larger collections representing multiple individuals and potential disease or health states. One common feature is the unexpected diversity of the microbiota at any of these locations, which poses a challenge for relating the microbiota to health and disease. However, we anticipate microbiota compositional measurements could become standard clinical practice in the future and may become diagnostic for certain diseases or increased susceptibility to certain disorders. The microbiota of a number of disease states are currently being examined to identify potential correlations. In line with these predictions, it is possible that existing conditions may be resolved by altering the microbiota in a positive way.


Mutational analysis of the androgen receptor gene in two Chinese families with complete androgen insensitivity syndrome.
Androgens are essential for normal male sex differentiation and are responsible for the normal development of male secondary sexual characteristics at puberty. The physiological effects of androgens are mediated by the androgen receptor (AR). Mutations in the AR gene are the most common cause of androgen insensitivity syndrome. The present study undertook a genetic analysis of the AR gene in two unrelated families affected by complete androgen insensitivity syndrome (CAIS) in China. In family 1, a previously reported nonsense mutation (G-to-A; p.W751X) was identified in exon 5 of the AR gene. In addition, a novel missense mutation was detected in exon 6 of the AR gene from family 2; this mutation resulted in a predicted amino acid change from phenylalanine to serine at codon 804 (T-to-C; p.F804S) in the ligand-binding domain (LBD) of AR. Computer simulation of the structural changes generated by the p.F804S substitution revealed marked conformational alterations in the hydrophobic core responsible for the stability and function of the AR-LBD. In conclusion, the present study identified two mutations from two unrelated Chinese families affected by CAIS. The novel mutation (p.F804S) may provide insights into the molecular mechanism underlying CAIS. Furthermore, it expands on the number of mutational hot spots in the international AR mutation database, which may be useful in the future for prenatal diagnosis and genetic counseling.


Alpha 1-adrenoceptor subtypes in aorta (alpha 1A) and liver (alpha 1B).
The effect of several alpha 1 adrenoceptor antagonists on the alpha 1-adrenoceptor-mediated stimulation of phosphatidylinositol labeling was studied comparatively in rat hepatocytes and rabbit aorta. It was observed that 5-methyl urapidil and WB 4101 were much more potent in rabbit aorta than in hepatocytes. The orders of potency were prazosin much greater than 5-methyl urapidil greater than or equal to WB 4101 in liver cells and WB 4101 greater than or equal to 5 methyl urapidil = prazosin in aorta. Treatment with chlorethylclonidine inhibited 70-80% of the stimulation of labeling induced by epinephrine in rat liver, but only 30-40% of that in aorta. Our data suggest the existence of two pharmacologically distinct receptors in these tissues i.e.m alpha 1A-adrenoceptors in aorta and alpha 1B in liver cells.


Serological markers in inflammatory bowel disease: the pros and cons.
Accurate serological assays are desirable for the diagnosis of inflammatory bowel disease. Among several serological markers anti-Saccharomyces cerevisiae mannan antibodies and perinuclear antineutrophil cytoplasmic autoantibodies are highly disease specific for Crohn's disease and ulcerative colitis, respectively. Combining the two improves their specificity. Sensitivity, however, is still low. Due to lack of standardization and vast interobserver variability, they cannot be used as the only diagnostic criteria but can assist clinicians in diagnosing and categorizing patients with inflammatory bowel disease as well as in helping them to take therapeutic decisions.


[Value of endosonography in diagnosis of diffusely growing stomach carcinomas].
The diagnosis of diffuse type gastric carcinoma is very difficult. The delay of diagnosis is often due to false-negative endoscopic and histologic evaluation. The architecture of the stomach can be clearly visualized by endosonography. Therefore, already minor destructions of the gastric layers can be found. The endosonographic picture includes the presence of the layers, which are larger and of irregular contour. In infiltrating gastric cancer typically the submucosal layer and the muscularis are concentrically enlarged and appear folded. Based on the endosonographic picture diffuse type gastric carcinoma has been diagnosed in 32 patients. When compared to the histologic diagnosis after gastrectomy or autopsy the accuracy of the endosonographic diagnosis was 87.5%, (28 out of 32 patients). From the remaining four patients diagnosed to have diffuse type gastric cancer by endosonography three patients turned out to have malignant infiltrating tumors of different histologies. Therefore, the positive predictive value of endosonography in detection of infiltrating malignant tumors was 96.8% in our group. In contrast the accuracy of preoperative histologic diagnosis by biopsies was only 58%. Suspicious results of gastroscopy, especially in combination with a negative biopsy, should lead to further evaluation by endosonography to detect diffuse type gastric cancer earlier.


Blood transfusion and survival after surgery for stage I and II breast cancer.
The records of 690 Stage I and II breast cancer patients (31% of them with transfusions), who underwent mastectomy with axillary dissection were examined whether perioperative blood transfusion might be detrimental to survival. The overall 5- and 10-year survival rates for 477 patients who had not received transfusions were 75% and 63% respectively, compared with 66% and 49% for those who had transfusions (p = 0.005). There was no significant difference between the groups in any other of the most important prognostic factors. An analysis of the subpopulation of patients with favorable prognostic factors yielded similar results. A multivariate analysis indicated that blood transfusion was one of the four variables significantly related to survival.


Cleavage of TRPM7 releases the kinase domain from the ion channel and regulates its participation in Fas-induced apoptosis.
Transient receptor potential melastatin-like 7 (TRPM7) is a channel protein that also contains a regulatory serine-threonine kinase domain. Here, we find that Trpm7-/- T cells are deficient in Fas-receptor-induced apoptosis and that TRPM7 channel activity participates in the apoptotic process and is regulated by caspase-dependent cleavage. This function of TRPM7 is dependent on its function as a channel, but not as a kinase. TRPM7 is cleaved by caspases at D1510, disassociating the carboxy-terminal kinase domain from the pore without disrupting the phosphotransferase activity of the released kinase but substantially increasing TRPM7 ion channel activity. Furthermore, we show that TRPM7 regulates endocytic compartmentalization of the Fas receptor after receptor stimulation, an important process for apoptotic signaling through Fas receptors. These findings raise the possibility that other members of the TRP channel superfamily are also regulated by caspase-mediated cleavage, with wide-ranging implications for cell death and differentiation.


Bacillus anthracis pXO1 plasmid encodes a putative membrane-bound bacteriocin.
Evolutionary advantages over cousin cells in bacterial pathogens may decide about the success of a specific cell in its environment. Bacteria use a plethora of methods to defend against other cells and many devices to attack their opponents when competing for resources. Bacteriocins are antibacterial proteins that are used to eliminate competition. We report the discovery of a putative membrane-bound bacteriocin encoded by the Bacillus anthracis pathogenic pXO1 plasmid. We analyze the genomic structure of the bacteriocin operon. The proposed mechanisms of action predestine this operon as a potent competitive advantage over cohabitants of the same niche.


Assessment of different loading doses of dexmedetomidine hydrochloride in preventing adverse reaction after combined spinal-epidural anesthesia.
We conducted the present study to investigate the effects of the different loading doses of dexmedetomidine hydrochloride in the prevention of adverse reactions after combined spinal-epidural anesthesia. A total of 200 patients that were admitted to the Department of Obstetrics at the Second Affiliated Hospital of Xi'an Jiaotong University hospital and treated with cesarean section through the use of combined spinal-epidural anesthesia from December, 2014 to June, 2016, were randomly divided into 4 groups. The therapeutic regimens of patients were shown as follows: group A was administered an intravenous pump of 10 ml/l physiological saline in surgery until the end of the delivery. group B was administered 0.2 µg/kg dexmedetomidine. group C was administered 0.4 µg/kg dexmedetomidine. group D was administered 0.6 µg/kg dexmedetomidine. The anesthesia plane was adjusted to the level below the T10 plane. After the onset of anesthesia, participants of each group were treated with an intravenous pump of dexmedetomidine at loading dose. After intravenous pumping for 10 min in each group during the surgery, patients were administered with an intraoperative maintenance dose of 0.2 µg/kg/h until the end of the delivery. The heart rate (HR), mean arterial pressure (MAP), Narcotrend index (NI), Ramsay sedation score and the incidence of adverse reactions at each time-point of the start of drug administration (T0), 10 min (T2), 30 min (T3), 60 min (T4), 90 min (T5) and the end of surgery (T6) were recorded. Within 24 h post-delivery, the degree of amnesia from using dexmedetomidine until the end of the delivery were followed up. Compared to group A and T0, the HRs of participants at T3-6 in groups B and C were decreased. The MAP at T1 in group D was increased. In groups B and C, the NIs were significantly decreased at T2-6, the Ramsay scores were increased at T3-6, and the differences were statistically significant (P<0.05). The follow-up within 24 h after delivery showed that the degree of anterograde amnesia from groups B to D was significantly higher than group A, with statistically significant difference (P<0.05). A combined spinal-epidural anesthesia with 0.6 µg/kg loading dose of dexmedetomidine, by intravenous pumping within 10 min before cesarean section, can achieve a satisfied sedative effect at 30 min after administration. It maintains the characteristics of intraoperative hemodynamic stability and less adverse reactions. Therefore, it is of great significance to improve the quality of cesarean section delivery.