Molecular Detection and Antimicrobial Resistance Patterns of Shiga Toxigenic Escherichia coli Isolated from Bovine Subclinical Mastitis Milk Samples in Kurdistan, Iran.
Bovine subclinical mastitis is regarded as a devastating disease due to the economic costs imposed on dairy husbandry. Moreover, it is a hazard in the public sector in the cases of zoonotic bacteria because of the potential role of unpasteurized milk and dairy products to propagate the infectious agent to the human food chain. The present study aimed to evaluate the frequency, virulence content, and antimicrobial resistance profile of Shiga toxin-producing Escherichia coli (STEC) strains isolated from bovine subclinical mastitis in Kurdistan Province, West of Iran. A total of 400 bovine subclinical mastitis milk samples recognized in the California Mastitis Test were collected aseptically and analyzed for the presence of E. coli phenotypically and molecularly. The isolates were genotypically screened for stx1, stx2, and eae genes. Furthermore, O157:H7 STEC strain was searched among the isolates in a duplex polymerase chain reaction. The antimicrobial resistance scheme of the isolates was determined using the agar disk diffusion method. In general, 173 (43.25%) E. coli isolates were detected among which 39 (22.54%) isolates were STEC. The frequency of STEC virulence genotypes was stx2 (25 isolates, 64.10%), stx2+eae (6 isolates, 15.38%), stx1+stx2 (6 isolates, 15.38%), and stx1+stx2+eae (2 isolates, 5.12%). In addition, three O157: H7 strains were identified with the genetic content of stx1+stx2+eae (2 isolates) and stx1+stx2 (1 isolate). The most prevalent antimicrobial resistance was observed against streptomycin, tetracycline, and ampicillin. Gentamycin, amoxicillin-clavulanic acid, and trimethoprim-sulfadiazine were the most effective antibiotics against O157 strains, whereas gentamycin, ciprofloxacin, and nitrofurantoin were effective against non-O157 strains. The results revealed the significant role of STEC in bovine subclinical mastitis in the studied region. In addition, the distribution of O157:H7 strain and high prevalence of multidrug resistance among the isolates is a matter of concern. Therefore, there is a potential threat of human infection following the consumption of contaminated milk with STEC in Kurdistan Province, Iran.


A generic model for 11C labelled radiopharmaceuticals for imaging receptors in the human brain.
A large number of radiopharmaceuticals labelled with 11C (half-time 0.340 h) are being developed for positron emission tomographic studies of different types of receptor in the human brain. For most of these agents, the available biokinetic data are insufficient to construct realistic compound-specific biokinetic models for calculating the internal radiation dose delivered to persons undergoing investigation. A generic model for brain receptor substances that predicts the internal dose with sufficient accuracy for general radiation protection purposes has, therefore, been developed. Biokinetic data for 13 11C-radiopharmaceuticals used clinically for imaging different brain receptors indicate that, despite differences in chemical structure, their uptake and retention in the human brain and other tissues are broadly similar. The proposed model assumes instantaneous deposition of 5% of the injected radioactivity in the brain, with the remaining radioactivity being rapidly and uniformly distributed throughout all other tissues. Elimination from all tissues is assumed to occur with a half-time of 2 h. It is further assumed that 75% of the injected 11C is excreted in the urine, and 25% via the gall bladder, with a half-time of 2 h. This model yields an effective dose of 4.5 x 10(-3) mSv MBq(-1), with doses of 3.2 x 10(-2), 1.7 x 10(-2), 8.7 x 10(-3), 5.2 x 10(-3), and 3.8 x 10(-3) mGy MBq(-1) to the urinary bladder, gall bladder, kidneys, brain and ovaries, respectively. These doses are well within the range of those reported using compound-specific models for the radiopharmaceutals studied.


Effect of common agonists on cytoplasmic ionized calcium concentration in platelets. Measurement with 2-methyl-6-methoxy 8-nitroquinoline (quin2) and aequorin.
Because of controversy regarding the relationship of cytoplasmic ionized calcium concentration ([Cai2+]) to platelet activation, we studied the correlation of platelet aggregation and ATP secretion with [Cai2+] as determined by 2-methyl-6-methoxy 8-nitroquinoline (quin2) and aequorin in response to ADP, epinephrine, collagen, the Ca2+ ionophore A23187, and thrombin. Both indicators showed a concentration-dependent increase in [Cai2+] in response to all agonists except epinephrine when gel-filtered platelets were suspended in media containing 1 mM Ca2+. With epinephrine, a rise in [Cai2+] was indicated by aequorin, but not by quin2; [Cai2+] signals, aggregation, and secretion were suppressed by EGTA. ADP [0.5 microM] produced a rise in [Cai2+] that was registered by both aequorin and quin2 in platelets in Ca2+-containing media; addition of EGTA to the medium raised the threshold concentration of ADP to 5.0 microM for both indicators. Collagen produced progressive concentration-related increases in [Cai2+] and aggregation in aspirin-treated aequorin-loaded platelets. Quin2 failed to indicate a rise in [Cai2+]at lower collagen concentrations with EGTA or aspirin. [Cai2+] response to A23187 and thrombin was reduced by addition of EGTA to platelets loaded with either aequorin or quin2. With all five agonists in all conditions tested, aequorin [Cai2+] signals occurred at the same agonist concentration as that or lower than that which produced platelet shape change, aggregation, or secretion. Platelet activation was better correlated with changes in [Cai2+] indicated by aequorin than with the response of quin2, possibly because aequorin is more sensitive to local zones of [Cai2+] elevation.


Intracranial transplant of olfactory ensheathing cells in children and adolescents with cerebral palsy: a randomized controlled clinical trial.
Successful repair of damage in cerebral palsy (CP) needs effective clinical interventions other than simply symptomatic treatments. To elucidate the feasibility of using olfactory ensheathing cells (OECs) to treat CP in children and adolescents, we conducted a randomized controlled clinical trial (RCT) on 33 patients. The patients were randomly assigned into two groups (treatment group, n = 18; control group, n = 15), and OECs derived from aborted fetal tissue were injected into the bilateral corona radiata in the frontal lobes (a key point for neural network restoration, KPNNR). The Gross Motor Function Measure (GMFM-66) and the Caregiver Questionnaire Scale were used to evaluate the patients' neurological function and overall health status. Among the 14 patients who completed the 6-month study, six received the cell transplantation and the other eight served as controls. In OEC treatment group, GMFM-66 scores were 26.67 +/- 25.33 compared with 19.00 +/- 20.00 for the control group. Concurrently, the Caregiver Questionnaire Scale score decreased to 77.83 +/- 15.99 in the treatment group in comparison to 138.66 +/- 64.06 of the control group. This trial, albeit small in sample size, indicates OEC KPNNR transplantation is effective for functional improvement in children and adolescents with CP, yet without obvious side effects. This small-scale study suggests that the procedure may be a plausible alternative method to treat this not yet curable disorder, and we urge further evaluation with a large-scale RCT.


Hierarchical processing of visual stimuli in nephropathic cystinosis.
Previous studies have shown that individuals with cystinosis may exhibit difficulty with visuospatial tasks. Global and local (hierarchical) processing are specific types of visuospatial tasks mediated by the right and left parietal lobes respectively. The study objective was to determine whether individuals with cystinosis and carriers of the cystinosin gene mutation show deficits in global and/or local processing. The study included 48 children (32 controls, 16 cystinosis) and 56 adults (25 controls, 25 carriers, and 6 cystinosis). Participants were instructed to replicate 10 hierarchical stimuli to assess global-local processing. The primary outcome measure was mean global and local performance on the hierarchical stimuli task between subgroups. Error subtypes were included to further assess each image. Compared to the control subgroups, adult and child cystinosis patients as well adult carriers demonstrated significant deficits in the global processing of a hierarchical stimulus against a background of unimpaired local processing. Child cystinosis patients performed significantly more poorly than controls on all error subtypes except local shape distortion. Adult cystinosis patients and carriers made significantly more global shape distortion errors than the controls. Our study shows that the cognitive profile documented in cystinosis patients and carriers includes significant difficulties with the global processing of an image. Results of the carrier population are important since they suggest that the cognitive impairments observed in patients cannot be attributed to symptomatic manifestations of the disease. Instead, the global processing deficits observed provide insight into the potential role of the cystinosin gene mutation on neurodevelopmental differences seen in these individuals.


Rabies in a blind patient: confusion after corneal transplantation.
Two blind persons received corneal transplants from a single donor who showed no signs of rabies before he died. One of the recipients, a young girl, died 16 days later of rabies and the other recipient survived. We discuss the possible mode of transmission of rabies to the first recipient and the management of the second recipient.


Scrotal circumference adjustment for differences due to age of beef bulls.
Scrotal circumference measurements on 870 Angus, 759 Polled Hereford, and 309 Simmental bulls ranging in age from 484 to 704 days were analyzed to develop an appropriate method of adjustment of scrotal circumference for differences associated with age of the bull. Data were separated by breed, year, and season and then each subset of data was subjected to statistical analysis. Adjustment factors to remove differences due to age were developed for bulls of the three breeds studied.


Antifungal activity of elutriated human monocytes against Aspergillus fumigatus hyphae: enhancement by granulocyte-macrophage colony-stimulating factor and interferon-gamma.
Human monocytes are important effector cells in host defenses against Aspergillus hyphae, and as elutriated monocytes (EHM) they may be transfused in large quantities to leukopenic patients with invasive aspergillosis. The antifungal activity of EHM against Aspergillus hyphae was compared with that of polymorphonuclear leukocytes (PMNL). The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) on superoxide anion (O2-) release and on hyphal damage caused by EHM against unopsonized A. fumigatus hyphae was investigated. EHM had antihyphal activity comparable to that of PMNL. GM-CSF significantly augmented O2- release by EHM in response to PMA. Also, both GM-CSF and IFN-gamma significantly enhanced the antifungal activity of EHM compared with untreated controls. Thus, EHM have demonstrable antifungal activity against Aspergillus hyphae that may be increased by GM-CSF and IFN-gamma, suggesting their potential therapeutic role in immune reconstitution of effector cells.


Observation of Clinicopathologic Features of Pituitary Adenoma With Neuronal Differentiation.
To investigate the clinicopathologic features of pituitary adenoma with neuronal differentiation. Four patients with mixed gangliocytoma-pituitary adenomas between January 2011 and January 2021 and 111 new-onset patients with adenomas between January 2019 and June 2021 who attended the First Affiliated Hospital of Fujian Medical University were included in the study. The histological and immunohistochemical findings were analyzed. Neuronal differentiation marker staining was performed on new-onset adenomas, and the related literature was reviewed. Altogether, more than 100 mixed gangliocytoma-pituitary adenoma cases have been reported in the literature until now, of which pituitary-specific POU-class homeodomain transcription 1 (PIT1) positive adenomas are more frequently observed. In the present study, all 4 patients we described were female, aged 29 to 53 years (mean 39 years). Clinically, 3/4 patients presented with acromegaly, and 1/2 patients presented with headache. Histologically, the tumor was composed of two distinct mixed components. The one was a population of neoplastic ganglionic cells with large nuclei, prominent nucleoli, and abundant basophilic cytoplasm embedded in a fibrillary background. Stains of chromograninA (CgA), synaptophysin (Syn), Calretinin (CR) were positive. Axotomy-like expression was observed in neurofilament (NF) staining. PIT1 was expressed in partial ganglionic cells in all cases. The other component was a population of small uniform cells with round nuclei and acidophilic cytoplasm. Prolactin (PRL) and growth hormone (GH) were positive in all 4 cases. PIT1 was positive in the nuclei of adenomas. Although adenomas and ganglionic regions varied in histology, there was a population of cells with neuronal differentiation expressing PIT1. Additionally, axotomy-like expression of NF staining could be seen in a distant area of adenoma regions. A total of 111 cases of adenomas without ganglionic cells were included in this study, including 7 cases with neuronal differentiation. Among them, 4 cases were prolactinomas, 2 cases were somatotroph adenomas, and 1 case was corticotroph adenoma. 6/7 cases were PIT1-positive adenomas. And the remaining one case is T-PIT-positive adenoma. Mixed gangliocytoma-pituitary adenomas are rare tumors with neuronal differentiation. The majority of MGAs are associated with endocrinopathies, mainly acromegaly. Our results suggest that PIT1-positive pituitary adenomas may have neural differentiation potential, which may not be unusual. This indication supports the possibility that the neuronal transdifferentiation of adenomatous cells is a possible mechanism, and the underlying mechanism requires further elucidation.


Multidrug resistance in haematological malignancies.
Many patients with haematological disorders develop resistance to the drugs used in the treatment of their condition. This resistance is often effective against a range of chemotherapeutic agents, hence the term multidrug resistance (MDR) is used. During the past ten years the mechanisms underlying the development of MDR have become better understood, and in this Review the current concepts of the factors contributing to MDR are examined.


Sustained low diffusing capacity in hepatopulmonary syndrome after liver transplantation.
To study the presence of sustained low diffusing capacity (DL(CO)) after liver transplantation (LT) in patients with hepatopulmonary syndrome (HPS). Six patients with mild-to-severe HPS and 24 without HPS who underwent LT were prospectively followed before and after LT at mid-term (median, 15 mo). HPS patients were also assessed at long-tem (median, 86 mo). Before LT, HPS patients showed lower PaO(2) (71 +/- 8 mmHg), higher AaPO(2) (43 +/- 10 mmHg) and lower DL(CO) (54% +/- 9% predicted), due to a combination of moderate-to-severe ventilation-perfusion (V(A)/Q) imbalance, mild shunt and diffusion limitation, than non-HPS patients (94 +/- 4 mmHg and 19 +/- 3 mmHg, and 85% +/- 3% predicted, respectively) (P<0.05 each). Seven non-HPS patients had also reduced DL(CO) (70% +/- 4% predicted). At mid- and long-term after LT, compared to pre-LT, HPS patients normalized PaO(2) (91 +/- 3 mmHg and 87 +/- 5 mmHg), AaPO(2) (14 +/- 3 mmHg and 23 +/- 5 mmHg) and all V(A)/Q descriptors (P<0.05 each) without changes in DL(CO) (53% +/- 8% and 56% +/- 7% predicted, respectively). Post-LT DL(CO) in non-HPS patients with pre-LT low DL(CO) was unchanged (75% +/- 6% predicted). While complete V(A)/Q resolution in HPS indicates a reversible functional disturbance, sustained low DL(CO) after LT also present in some non-HPS patients, points to persistence of sub-clinical liver-induced pulmonary vascular changes.


Influences on colonic and small intestinal motility by the cerebellar fastigial nucleus.
The fastigial influence on intestinal motility was investigated in acute experiments on chloralosed cats. Motility was recorded both from the small and large intestine. Electrical stimulation of the rostral fastigial pole produced, in combination with a blood pressure rise, increased motor activity in ileum and colon while jejunum could respond with either increased on decreased motility. The intestinal responses were neither secondary to changes in intestinal blood flow, nor to baroreceptor reflexes induced by the increased blood pressure. The excitatory responses were not due to increased parasympathetic activity since sectioning of such pathways failed to abolish the responses. Instead, interruption of adrenergic sympathetic discharge, accomplished either by guanethidine or by sectioning of relevant nerves, aid eliminate the responses, indicating that the fastigial effects were mediated by suppression of prevailing adrenergic tone. Noxious stimuli to the abdomen, including laparotomy, inhibit intestinal motility by a reflex increase in adrenergic discharge. It is suggested that fastigial influence on intestinal motility is mainly due to suppression of this reflex.


BOAR: Biprism based optical autocorrelation with retrieval.
A simple and compact single-shot autocorrelator is presented and analyzed in detail. The autocorrelator is composed of two elements only: a Fresnel biprism used to create two temporally delayed replicas of the pulse to characterize and a camera in which two-photon absorption takes place. The two-photon absorption signal obtained in the camera can be used to retrieve the pulse duration, the frequency chirp, and the pulse spectrum, provided that a Gaussian temporal shape is assumed. Thanks to its extreme simplicity, the autocorrelator is robust and easy to align. The presented design can theoretically characterize the pulse duration from about 25 fs to 1.5 ps in the two-photon spectral range of the camera (1200-2400 nm). Finally, a proof-of-principle demonstration is also performed at 3.1 μm by using an InGaAs camera, whose two-photon spectral range is located further in the infrared (1800-3400 nm).


Prevalence of Plasmodium species in Badr Governorate, Madinah Province, Saudi Arabia using microscopy and rapid diagnostic test.
Malaria infection still represents a notable public health risk in Saudi Arabia. This cross-sectional study aimed to determine the prevalence of Plasmodium species among clinically suspected cases who presented at Badr General Hospital and healthcare facilities in selected regions of Badr Governorate, Madinah Province, Saudi Arabia between January 2021 and January 2022. A total of 493 suspected patients were recruited from Badr Governorate, investigated for malaria infection using CBFME and rapid diagnostic test- CareStart Malaria Pf/PAN (HRP2/pLDH) Ag Combo rapid diagnostic tests. The results showed that malaria infection was 34 (6.89%) cases among 493 suspected patients using microscopic examination as reference test. Moreover, subjects aged 31 to 40 years and those aged 51 to 60 years had the highest (50%) and lowest (8.82%) percentages of malaria cases. Plasmodium vivax (19/34, 55.88%) was higher than P falciparum (15/34, 44.1%) as the causative agents of malaria cases. The majority of malaria cases (29/34, 80.9%) among non-Saudi mainly from Sudan (15/34, 44.1%), Pakistan (5/34, 14.7%), Bangladesh (5/34, 14.7%) and India (4/34, 11.76%) whereas malaria cases among Saudis (5/34, 14.7%). In addition, the majority of malaria cases (32/34, 94.11%) among male subjects while (2/34, 5.88%) among females. The current study revealed that malaria transmission is still active in Badr Governorate, Madinah Province, Saudi Arabia and represents a public health concern. Further screening implements and continuous epidemiological monitor of the status of malaria infection in Kingdom of Saudi Arabia are thus warranted to improve its controlling activities and eradicate malaria endemicity in the country.


Spinal cord infarction mimicking ischemic heart disease.
Spinal cord infarction is a rare condition and is easily misdiagnosed owing to its initial non-specific manifestation. We report a case of a 77-year-old man who presented with chest pain and upper back pain initially, and was misdiagnosed with a myocardial infarction. Four hours after admission, he complained of numbness in his entire left leg below the knee, with rapid deterioration of neurological symptoms. After 9 hours, loss of sensation progressed up to the T4 dermatome, strength of both lower extremities deteriorated to grade 0, and decrease in anal tone and deep tendon reflex was observed. Initial magnetic resonance imaging findings were normal; however, a signal change occurred 3 days after symptom onset. When patients present with acute chest pain and neurologic symptoms, the possibility of ischemic cardiac disease as well as any neurological manifestations must be investigated. Emergency physicians must remember the value of serial physical examinations.


Study on the Up-Conversion Luminescence and Conductivity Behavior of p-Type NiO:Yb,Er Thin Films.
In this work, Li+-doped NiO:Yb,Er thin films are obtained via pulsed laser deposition. It was found that the films exhibit high transparency in the visible region and clearly red up-conversion luminescence under 980 nm excitation. Doping with Li+ can adjust the up-conversion emission intensity of the films. Moreover, all the films have p-type conductivity with a single activation energy of around 360 meV. The sheet resistivity of the films can be improved through changing the doping concentration of Li+ ions. Taken together, 5% is the best doping concentration for the potential application of this kind of film.


Role of cytokines in development of pre-eclampsia associated with periodontal disease - Cohort Study.
The present study was designed to find any association of cytokines in women with periodontal disease and development of pre-eclampsia in North Indian population. A total of 504 consecutively registered primigravida with a single live pregnancy were recruited at 14-18 weeks of gestation from antenatal clinic of Maulana Azad Medical College & associated Lok Nayak Hospital and Maulana Azad Institute of Dental Sciences, New Delhi. One periodontist performed oral health examination of all patients at inclusion into study. Blood samples were collected to measure the level of cytokines IL-4, IL-10, TNF-α and IFN-γ. The profile of blood levels of cytokines from women with periodontal disease was observed. The log serum levels of TNF-α & IL-4 at 16-18 weeks of gestation were significantly higher in women with periodontal disease (4.13 ± 2.06; 0.47 ± 1.56 pg/ml respectively) than in women with healthy gums (2.16 ± 1.51; 0.02 ± 1.84 pg/ml respectively, p < 0.001). Periodontal disease is associated with log serum TNF-α levels at cut-off ≥14.43 pg/ml at sensitivity 71.2% and specificity 62% (OR = 4.04; 95%CI = 2.77-5.87). Woman with periodontal disease who later developed pre-eclampsia had lower levels of TNF-α (3.72 ± 1.33 pg/ml) than those with periodontal disease who did not develop pre-eclampsia (4.20 ± 2.15 pg/ml, p ≥ 0.05). Reduced TNF-α level secretion in the early second trimester in women with periodontal disease appears to be associated with the development of pre-eclampsia.


Preparative isolation of cerebrosides (galactosyl and glucosyl ceramide).
An improved method for isolating cerebrosides from natural sources is described. The method is particularly suited to large scale work and can be adapted to the isolation of sphingolipids that are less polar than the gangliosides. It is based on the use of sodium sulfate to absorb the water from chloroform-methanol tissue extracts, the use of triiodide to cleave the ether linkage of plasmalogens, and the use of alkaline methanolysis to cleave the ester linkages of the glycerolipids. The final separation of the lipids is done with a silica gel column.


Mortality and morbidity from invasive bacterial infections during a clinical trial of acellular pertussis vaccines in Sweden.
A double blind placebo-controlled efficacy trial of two acellular pertussis vaccines was conducted in 3801 6- to 11-month-old children. Four vaccinated children died during 7 to 9 months follow-up as a result of Haemophilus influenzae type b meningitis, heroin intoxication with concomitant pneumonia, suspected septicemia, and Neisseria meningitidis Group B septicemia. From the actual death rate in children belonging to the same birth cohort in Sweden that could have been eligible for the trial, one death was expected among vaccinated children. Several investigations were carried out to examine the possibility that the deaths could be causally related to the vaccination. The relative risk for hospitalization due to systemic or respiratory infections was 1.07 (95% confidence interval, 0.95 to 1.20) and 0.83 (95% confidence interval, 0.64 to 1.08) in the vaccine groups as compared with the placebo group. Subsets of the population were studied for signs of immunosuppression. There was no indication of immunoglobulin deficiency or any sign of clinically significant leukopenia or lymphocytosis in vaccine recipients. The results of this analysis provide no evidence for a causal relation between vaccination with the studied acellular pertussis vaccines and altered resistance to invasive disease caused by encapsulated bacteria. The hypothesis that the two variables are related, however, cannot be refuted from these data.


Continuous passages accelerate the reprogramming of mouse induced pluripotent stem cells.
Induced pluripotent stem cells (iPSCs) are usually generated by reprogramming somatic cells through transduction with a transcription factor cocktail. However, the low efficiency of this procedure has kept iPSCs away from the study of the clinical application of stem cell biology. Our research shows that continuous passage increases the efficiency of reprogramming. Compared with conventional method of establishment of iPSCs, more embryonic stem cell (ESC)-like clones are generated by continuous passage during early reprogramming. These inchoate clones, indistinguishable from genuine ESC clones, are closer to fully reprogrammed cells compared with those derived from classical iPSC induction, which increased the expression of pluripotent gene markers and the levels of demethylation of Oct4 and Nanog. These results suggested that full reprogramming is a gradual process that does not merely end at the point of the activation of endogenous pluripotency-associated genes. Continuous passage could increase the pluripotency of induced cells and accelerate the process of reprogramming by epigenetic modification. In brief, we have provided an advanced strategy to accelerate the reprogramming and generate more nearly fully reprogrammed iPSCs efficiently and rapidly.


Genetic Polymorphisms and the Clinical Response to Systemic Lupus Erythematosus Treatment Towards Personalized Medicine.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a broad spectrum of clinical manifestations, an aberrant autoimmune response to self-antigens, which affect organs and tissues. There are several immune-pathogenic pathways, but the exact one is still not well known unless it is related to genetics. SLE and other autoimmune diseases are known to be inseparable from genetic factors, not only pathogenesis but also regarding the response to therapy. Seventy-one human studies published in the last 10 years were collected. Research communications, thesis publication, reviews, expert opinions, and unrelated studies were excluded. Finally, 32 articles were included. A polymorphism that occurs on the genes related to drugs pharmacokinetic, such as CYP, OATP, ABC Transporter, UGT, GST or drug-target pharmacodynamics, such as FCGR, TLR, and BAFF, can change the level of gene expression or its activity, thereby causing a variation on the clinical response of the drugs. A study that summarizes gene polymorphisms influencing the response to SLE therapy is urgently needed for personalized medicine practices. Personalized medicine is an effort to provide individual therapy based on genetic profiles, and it gives better and more effective treatments for SLE and other autoimmune disease patients.


Solid Phase Photothermo-Induced Chemical Vapor Generation: A New Desorption Method for Mercury Analysis by High-Throughput 20-Fiber Direct Immersion Solid Phase Microextraction.
A simple solid phase photothermo-induced chemical vapor generation (SP-PT-CVG) is described and used as an environmentally friendly desorption method for the sensitive determination of mercury in water by direct immersion solid phase microextraction (DI-SPME) atomic fluorescence spectrometry (AFS). A DI-SPME array equipped with 20 nano-TiO2-coated tungsten fibers was employed to simultaneously preconcentrate mercury from 20 samples, enabling an extraction throughput of 40 samples per hour. Subsequently, the fibers were drawn from the sample solutions and inserted into an inner tube sealed in a specially designed UV lamp in turn for SP-PT-CVG to generate Hg0, which was swept to an AFS detector for its detection. It is worth noting that the tube served as both a vapor generator and a desorption chamber. This proof-of-concept study confirms the feasibility of solid phase CVG. Compared to conventional CVG carried out in the liquid phase, solid phase CVG not only retains the advantages of conventional CVG but also alleviates the matrix interference on vapor generation and preconcentrates analyte prior to vapor generation, improving analytical performance for liquid state samples. DI-SPME-SP-PT-CVG-AFS provides a limit of detection of 2.3 ng L-1 for mercury determination by AFS. In the proposed method, the combination of DI-SPME and SP-PT-CVG eliminates the tedious derivatization steps required in conventional headspace SPME, thus minimizing toxic reagent consumption and improving extraction throughput. The practicality of DI-SPME-SP-PT-CVG-AFS was evaluated by analyzing two different certified reference materials and river water samples with good spike recoveries (98-107%).


Immunogenicity and reactogenicity of lowered doses of rhesus rotavirus vaccine strain MMU 18006 in young children.
Rhesus rotavirus oral vaccine strain MMU 18006 at a dose of 10(5) plaque-forming units (PFU), a 1:10 dilution of the original undiluted vaccine, is highly immunogenic in young children. Fevers have occurred, however, on Days 3 and 4 following vaccination. This study was conducted to determine whether febrile reactions could be eliminated and immunogenicity maintained by (1) giving smaller doses of vaccine or (2) vaccinating younger infants. Thirty-one children between 3 and 11 months of age received, in a randomized, double blind manner, either 10(4) PFU of vaccine virus, 10(3) PFU of vaccine virus or placebo. All recipients of the 10(4) PFU dose had a seroresponse; however, some degree of immunogenicity was lost with the smaller dose (10(3) PFU). Fevers were observed in recipients of both of the lowered doses of vaccine but the febrile reactions were related to the age of the vaccinee. No infant younger than 5 months of age experienced a temperature elevation, whereas the majority of children older than 5 months had fevers. Our data suggest that the lack of reaction in the younger infants correlates with the presence of prevaccination neutralizing antibody, presumably transplacentally acquired. We conclude that the rhesus rotavirus oral vaccine at a dose of 10(4) PFU is immunogenic and appears to be safe in young infants.


Nonlinear optical microscopy reveals invading endothelial cells anisotropically alter three-dimensional collagen matrices.
The interactions between endothelial cells (ECs) and the extracellular matrix (ECM) are fundamental in mediating various steps of angiogenesis, including cell adhesion, migration and sprout formation. Here, we used a noninvasive and non-destructive nonlinear optical microscopy (NLOM) technique to optically image endothelial sprouting morphogenesis in three-dimensional (3D) collagen matrices. We simultaneously captured signals from collagen fibers and endothelial cells using second harmonic generation (SHG) and two-photon excited fluorescence (TPF), respectively. Dynamic 3D imaging revealed EC interactions with collagen fibers along with quantifiable alterations in collagen matrix density elicited by EC movement through and morphogenesis within the matrix. Specifically, we observed increased collagen density in the area between bifurcation points of sprouting structures and anisotropic increases in collagen density around the perimeter of lumenal structures, but not advancing sprout tips. Proteinase inhibition studies revealed membrane-associated matrix metalloproteinase were utilized for sprout advancement and lumen expansion. Rho-associated kinase (p160ROCK) inhibition demonstrated that the generation of cell tension increased collagen matrix alterations. This study followed sprouting ECs within a 3D matrix and revealed that the advancing structures recognize and significantly alter their extracellular environment at the periphery of lumens as they progress.


Mandibular nerve block treatment for trismus associated with hypoxic-ischemic encephalopathy.
We describe the use of mandibular nerve block for the management of bilateral trismus associated with hypoxic-ischemic encephalopathy. The patient was a 65-year-old man with bilateral trismus due to hypoxic-ischemic encephalopathy. Despite his impaired consciousness, we performed fluoroscopically guided bilateral mandibular nerve block. The bilateral symptoms were sufficiently improved, without obvious side effects, by injecting a local anesthetic near the right mandibular nerve and a neurolytic near the left mandibular nerve. Mandibular nerve block may be an effective treatment for patients with bilateral trismus due to ischemic-encephalopathy, even when consciousness is impaired.


Direct evidence for BBSome-associated intraflagellar transport reveals distinct properties of native mammalian cilia.
Cilia dysfunction underlies a class of human diseases with variable penetrance in different organ systems. Across eukaryotes, intraflagellar transport (IFT) facilitates cilia biogenesis and cargo trafficking, but our understanding of mammalian IFT is insufficient. Here we perform live analysis of cilia ultrastructure, composition and cargo transport in native mammalian tissue using olfactory sensory neurons. Proximal and distal axonemes of these neurons show no bias towards IFT kinesin-2 choice, and Kif17 homodimer is dispensable for distal segment IFT. We identify Bardet-Biedl syndrome proteins (BBSome) as bona fide constituents of IFT in olfactory sensory neurons, and show that they exist in 1:1 stoichiometry with IFT particles. Conversely, subpopulations of peripheral membrane proteins, as well as transmembrane olfactory signalling pathway components, are capable of IFT but with significantly less frequency and/or duration. Our results yield a model for IFT and cargo trafficking in native mammalian cilia and may explain the penetrance of specific ciliopathy phenotypes in olfactory neurons.


Reducing sexual risk and promoting acceptance of men who have sex with men living with HIV in India: Outcomes and process evaluation of a pilot randomised multi-level intervention.
HIV-positive men who have sex with men (HIV+MSM) in India need culturally-relevant interventions to promote safer sex. We tested a multi-level intervention among HIV+MSM that targeted individual, interpersonal, and community factors, based on the Social-Personal and Social Ecological Models. We conducted a 2 × 2 factorial RCT with 119 HIV+MSM randomised to receive either an individual-level intervention (ILI) using motivational interviewing to promote safer sex, a community-level intervention (CLI) to strengthen community norms toward safer sex and reduce stigma among MSM communities, a multi-level intervention combining the individual- and community-level interventions (ILI + CLI), or standard-of-care control. Participants completed pre- and post-intervention assessments of a composite sexual risk score and a process evaluation to assess fidelity and satisfaction. Out of the 119 HIV+MSM, 106 (89.0%) completed pre- and post-intervention assessments. Generalised Estimating Equation models showed that both CLI (Incidence Rate Ratio [IRR] = .67, 95% CI .47 to .96) and ILI + CLI (IRR = .66, 95% CI .48 to .91) groups had a statistically significant decrease in sexual risk compared to the standard-of-care. The interventions had high levels of fidelity and satisfaction. This pilot RCT demonstrated feasibility and potential effectiveness of a multi-level intervention that addresses individual, interpersonal and community-level contributors of sexual risk among HIV+MSM.


Talis pater, talis filius: perceived resemblance and the belief in genetic relatedness.
People hardly ever realize that their belief in their high rate of success in detecting family resemblances is affected by their knowledge of the actual genetic link between individuals. In the three studies reported here, 100 men and 100 women were requested to estimate the facial resemblance of photographically portrayed child-adult pairs, while being given either truthful or deceitful information, or no information, about their relatedness. Believing that the members of a pair were parent and offspring was the main predictor of the perceived similarity between them. Men and women agreed in judging children as more similar to female than to male adults, except when the pair members were believed to be related; in this case, men judged the child as resembling the alleged parents equally. Common remarks on family resemblance thus appear to ensue less from a conscious desire to please or reassure the parents than from general hypothesis-testing biases in human reasoning, made perhaps more specific in men by a concern with the problem of uncertain paternity.


Synergistic effect of a novel autophagy inhibitor and Quizartinib enhances cancer cell death.
Drug combinations have been increasingly applied in chemotherapy as a strategy to enhance the efficacy of anti-cancer treatment. The appropriate drug combinations may achieve synergistic effects beyond monotherapies alone. AC220 (Quizartinib), an FLT3 receptor tyrosine kinase inhibitor, developed for the treatment of AML, has been tested in phase II human clinical trials. However, AC220 as a monotherapy is not efficacious enough. In this study, we performed a small-molecule screening of 12 640 compounds in order to find a compound that increase the AC220 efficacy in chemotherapy. We identified that TAK-165, a HER2 inhibitor, even when used at low nanomolar doses in combination with AC220, was able to induce cell death in different cancer cells, but not in non-cancer cell lines. We showed that TAK-165 and AC220 act synergistically to downregulate key signaling pathways and potently induce cancer cell death. Furthermore, we demonstrated that TAK-165 inhibited autophagy in a HER2-independent manner. Finally, we showed that the combination of TAK-165 and AC220 induced cell death in cancer cells through the activation of chaperone-mediated autophagy. Overall, these findings support the strategy for using AC220 and an autophagy inhibitor such as TAK-165 in a combinatorial treatment to enhance the efficacy of cancer therapies.


Subpopulations of the T4+ inducer T cell subset in man: evidence for an amplifier population preferentially expressing Ia antigen upon activation.
Prior studies demonstrated that Ia molecules were expressed on a fraction of human peripheral T4+ inducer cells upon stimulation by soluble antigen. In the present study, we utilized a fluorescence-activated cell sorter to separate antigen-activated T4+,Ia+ and T4+,Ia- populations and characterized their function. It was found that the T4+,Ia+ population contained the majority of proliferating T cells as assessed by tritiated thymidine incorporation. This proliferation largely appeared to be nonspecific. Despite macrophage repletion, elimination of the Ia+ subset of T cells with monoclonal anti-Ia antibody and complement treatment equally diminished subsequent proliferation to both the triggering antigen and an unrelated antigen. Moreover, the antigen-induced Ia+ subset of T cells alone produced a nonspecific helper factor, LMF. In contrast, the the T4+,Ia- population showed minimal proliferation to soluble antigen and did not generate LMF. Nevertheless, both T4+,Ia+ and T4+,Ia- inducer T cells were required to generate maximal immunoglobulin production by B cells in an antigen-driven system. We conclude that the human T4+ inducer T cell subset is comprised of at least 2 functionally distinct subpopulations, which are capable of acting in a synergistic fashion to provide help to B cells.


Liquid biopsy in breast carcinoma: Are we there yet?
Breast carcinoma is the most common malignancy among women worldwide. Liquid biopsy is a method of obtaining tumour-derived material from blood and body fluid. This includes the assessment of circulating tumour cells (CTCs), circulating tumour deoxyribose nucleic acid (ctDNA), tumour educated platelets (TEPs) and exosomes. Detection of CTCs and ctDNA in liquid biopsy has been shown to have prognostic and predictive value in both early and metastatic breast carcinoma. The study of CTCs could also advance our understanding of aspects of tumour biology, including epithelial mesenchymal transition. ctDNA can be used to assess and monitor the molecular profile of breast carcinoma. It may help detect new genetic alterations in tumours and predict disease progression before the onset of clinical features or radiological evidence. TEPs and exosomes are also emerging as diagnostic, prognostic and predictive markers of breast carcinoma. Thus, liquid biopsy provides a non-invasive, repeatable method for the dynamic assessment of the tumour. Many methods have been used for the detection of CTCs and ctDNA. Most of these are still in the research stage and only the CellSearch method for the detection of CTCs and Therascreen PIK3CA RGQ polymerase chain reaction (PCR) assay for the detection of PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha) mutations in liquid biopsy have approval of the United States, Food and Drug Administration. However, their high costs, lack of standardized procedures, and a long and complicated detection process have limited their use. Despite its limitations, liquid biopsy is a useful tool in clinical decision making and has the potential to play an increasingly important role in the management of breast carcinoma in the future as we move toward more personalized cancer care.


Anticipation of Monetary Reward Can Attenuate the Vigilance Decrement.
Motivation and reward can have differential effects on separate aspects of sustained attention. We previously demonstrated that continuous reward/punishment throughout a sustained attention task improves overall performance, but not vigilance decrements. One interpretation of these findings is that vigilance decrements are due to resource depletion, which is not overcome by increasing overall motivation. However, an alternative explanation is that as one performs a continuously rewarded task there are less potential gains/losses as the task progresses, which could decrease motivation over time, producing a vigilance decrement. This would predict that keeping future gains/losses consistent throughout the task would reduce the vigilance decrement. In the current study, we examined this possibility by comparing two versions (continuous-small loss vs. anticipate-large loss) of a 10-minute gradual onset continuous performance task (gradCPT), a challenging go/no-go sustained attention task. Participants began each task with the potential to keep $18. In the continuous-small-loss version, small monetary losses were accrued continuously throughout the task for each error. However, in the anticipate-large-loss version, participants lost all $18 if they erroneously responded to one target that always appeared toward the end of the vigil. Typical vigilance decrements were observed in the continuous-small-loss condition. In the anticipate-large-loss condition, vigilance decrements were reduced, particularly when the anticipate-large loss condition was completed second. This suggests that the looming possibility of a large loss can attenuate the vigilance decrement and that this attenuation may occur most consistently after sufficient task experience. We discuss these results in the context of current theories of sustained attention.


Frailty assessment of older patients in the emergency department.
An ageing population is leading to an increase in patients attending emergency departments (EDs) with comorbidities and age-related syndromes such as frailty. Frailty is a clinical syndrome defined as an increased vulnerability to age-related or disease-related insults in older adults due to diminishing physiological reserves. It also places increased demands on staff and hospital services. Screening for frailty early in the care pathway ensures goal-directed and timely care. This article provides an overview of frailty and its assessment in older people presenting to the ED. It discusses the most commonly used frailty assessment tool in the ED, the Clinical Frailty Scale, and identifies that the results of frailty assessment should be used to initiate appropriate individualised care in older patients.


Aframomum stipulatum (Gagnep) K. Schum and Aframomum giganteum (Oliv. & Hanb) K. Schum as Aroma Tincto Oleo Crops resources: essential oil, fatty acids, sterols, tocopherols, and tocotrienols composition of different fruit parts of Congo varieties.
Today, few known plant species provide both an essential oil (EO) and a vegetable oil (VO). Seed and husk of two Aframomum species were investigated and compared in terms of EO, fatty acids, tocopherols, and tocotrienols. EO yield reaches 15.3 g kg(-1) in the seeds and 3.2 g kg(-1) in the husks, while VO yield is 180.0 g kg(-1) in the seeds and 25.0 g kg(-1) in the husks. β-Pinene, 1,8-cineol, α-selinene, terpine-4-ol, linalool, myrtenal and β-caryophyllene are the major compounds of seed and husk EO. Fatty acid analysis of two Aframomum species shows that oleic, linoleic, and palmitic acids were the major compounds of VO. Total sterol contents reached 4.3 g kg(-1) in seed VO and 8.5 g kg(-1) in husk VO. An appreciable amount of tocopherols (0.52 g kg(-1) ) was found in seed VO. The seed and husk oil of A. stipulatum and A. giganteum fruits are rich sources of many bioactive constituents such as fatty acids, sterols, tocopherols and tocotrienols. These tropical wild fruits can be considered as new Aroma Tincto Oleo Crops (ATOC) resources that contain both EOs and VOs.


[Prophylaxis of acute respiratory infections in children's collectives: results of treatment with nasal and nasopharyngeal irrigation].
The aim of this paper is to report the results of a multicenter open randomized clinical study of the efficacy of nasal and nasopharyngeal irrigation for the prevention of seasonal morbidity due to acute respiratory infections (ARIs) in the groups of preschool and school children. A total of 2386 children attending secondary schools and 519 ones attending kindergartens were examined. The study has demonstrated that irrigation of the nasal cavity and nasopharynx efficaciously reduces (by 2.4-3.2 times) the morbidity due to ARIs in organized children's collectives throughout the entire length of the epidemiological period; moreover, it improves the clinical course of ENT organ diseases and bronchial asthma.


[Exosome: Trojan horse in immunotherapy].
Exosomes are small membrane-bound vesicles that are secreted by a multitude of eukaryocytes as a consequence of fusion of multivesicular bodies with the plasma membrane. Exosomes can play critical roles in different physiological processes depending on their origins. Exosomes secreted from professional antigen-presenting cells are enriched in MHC class I and II complexes, costimulatory molecules, hsp 70 and hsp 90 chaperones, therefore exosomes, like Trojan horse, are of importance of immunoregulation in vivo and in vitro. The review will present current trends of research on the fundamental properties, production and purification of exosomes, and will focus on their implementation in cancer and virus immunotherapy as a novel cell-free peptide-based vaccine.


[Current technology development for natural orifice transluminal endoscopic surgery].
Natural orifice transluminal endoscopic surgery (NOTES) is a novel concept which combines aspects of flexible endoscopy with laparoscopic surgery with the aim of creating a new field of patient friendly "incisionless" surgery. This will require novel advanced technologies to be developed specifically for NOTES. We discuss the technical requirements and the process of creating NOTES instrumentation and illustrate the process with some current enabling devices. The development process is outlined, including the requirements for NOTES, the current technology that can be used, and some prototype devices for access, retraction, and tissue approximation. Endoscopes for NOTES must have high resolution, large instrument channels, some degree of triangulation, and the ability to lock into position inside the abdominal cavity. Instrumentation should echo the capabilities of current laparoscopic tools. They should be large and sturdy, torque-able, and offer the full spectrum of end-effectors. Finally, NOTES technology must permit secure, tailorable tissue approximation. The "R" scope from Olympus and the Transport scope from USGI Medical are possible solutions to the design requirements for access and visualization. Eagle Claw (Olympus), The Swain system (Ethicon), and the G-prox (USGI) are current tissue approximation systems under development and investigation in clinical trials. NOTES is a potential advance in surgical care. This new approach requires the development of new platform devices, tailored to allow the safe and effective practice of this advanced endoscopic approach.


Effect of local anaesthetic combined with wound cauterisation on the cortisol response to dehorning in calves.
To reassess whether local anaesthesia before dehorning and wound cauterisation after dehorning eliminates the cortisol response to dehorning. A control group was compared with three dehorned groups (dehorned alone, dehorned after local anaesthesia, dehorned after local anaesthesia then cautery of the amputation wounds). The local anaesthetic regimen used produced nerve blockade for about 5 h. Blood samples were taken before and after dehorning and plasma cortisol concentrations were determined. Dehorning caused a marked cortisol response lasting for about 7 h. Local anaesthetic reduced the plasma cortisol concentrations to control values for 5 h, after which they increased for a further 5 h. Subsequently in both groups, cortisol concentrations remained at control values until at least 24 h after treatment. Local anaesthetic combined with wound cautery virtually abolished the cortisol response until at least 24 h after dehorning. Combining local anaesthesia with cautery of the amputation wounds substantially reduced the cortisol response until at least 24 h after dehorning.


Symmetry in vertical ground reaction force is not related to walking and balance difficulties in people with multiple sclerosis.
Analysis of vertical ground reaction force (GRF) symmetry may benefit people with multiple sclerosis (PwMS) since it can detect important differences in gait mechanics which have not previously been discussed in the related literature. Therefore, the primary objective of the current study was to determine whether symmetry of the vertical GRF during gait is associated with validated gait and balance tests in PwMS. Additionally, we examined whether the symmetry of the vertical GRF differs between MS fallers, non-fallers and between neurological disability levels. Gait and balance data were collected from 402 PwMS (249 women) with a mean age of 42.1 (S.D=14.1) years. Vertical GRF parameters were obtained using the Zebris FDM-T Treadmill (Zebris Medical GmbH, Germany). Clinical gait and balance tests included the 2 and 6-min Walk Test, Timed Up and Go Test, Timed 25 Foot Walk, Four Square Step Test, Multiple Sclerosis Walking Scale questionnaire, Modified Fatigue Impact Scale and the Falls Efficacy Scale International questionnaire. The vertical GRF symmetry index score of the total sample was 3.7 (SD=3.1). In terms of fall status, non-significant differences were observed between the fallers and non-faller groups and between the neurological disability subgroups. Non-significant correlation scores were found between the vertical GRF symmetry index, all clinical walking and balance tests and self-reported questionnaires. We suggest clinicians, especially those involved in physical rehabilitation, accord low priority to this gait phenomenon in the MS population.


Incidence and clinical manifestations of HIV-1 infection in multitransfused thalassaemic Indian children.
Four hundred and six multitransfused thalassaemic children attending the paediatric clinic in Manipur, India, were screened for HIV antibodies. There were 46 (8.9%) ELISA antibody-positive children and the diagnosis was reaffirmed by Western blot assay. The immunologic status of the seropositive children was evaluated by a) absolute lymphocyte count, b) percentage of ratio of T helper (CD4+) and T suppressor (CD8+) cells, c) quantitative Ig, G, M and A levels and d) delayed-type cutaneous hypersensitivity (DTH) testing. Twelve of the 36 seropositive children were clinically symptomatic with AIDS. The clinical and immunological status of seropositive children are compared with matched seronegative thalassaemic control groups. Five of the 12 symptomatic seropositive children had received continued antiretroviral treatment. The mortality rate at the end of 36 weeks of itinerary was 20% in contrast to 50% in the untreated children. This report highlights the value of early recognition and therapeutic intervention in a selected high risk paediatric population.


Generation of digoxigenin-incorporated probes to enhance DNA detection sensitivity.
Telomere length in humans has been correlated with cancer and age-related diseases. The standard method to measure telomere length relies on Southern blot analysis with radioactively or non-radioactively labeled probes containing several telomeric DNA repeats. However, this approach requires relatively large amounts of genomic DNA, making it difficult to measure telomere length when a limited amount of sample is available. Here, we describe a non-radioactive labeling method that uses 3' fill-in combined with lambda exonuclease digestion to incorporate one or more digoxigenin (DIG) molecules into bridged nucleic acid (BNA)-containing oligonucleotides (ONTs). Using our method, we were able to generate probes to detect both C- and G-rich telomeric DNA strands. Compared with commercially available DIG-labeled telomere probes, probes generated using this new approach significantly enhance the sensitivity of telomere length measurements.


Diabetic neuropathy status and the concerns in underserved rural communities: challenges and opportunities for diabetes educators.
The purpose of this study was to investigate the prevalence of diabetic peripheral neuropathy (DPN) and to identify at risk populations in medically underserved rural communities. A cross-sectional study was conducted in 816 type 2 diabetic patients from 5 rural Arkansas counties who attended a diabetes education program from 2005 to 2009. The data was collected through a survey questionnaire and from medical records. Univariate and multivariate analyses were conducted. Of the 816 patients studied, 9.6% had a DPN diagnosis, and 43% reported peripheral neuropathy symptoms (PNS). Among the patients with PNS, 79% had not been diagnosed with DPN. Multivariate analyses found that being female, being white, having less than a college education, having a longer duration of diabetes, having a history of smoking, having a professional foot examination, and performing self foot examinations are associated with a higher risk for having DPN or PNS. The study found that the prevalence of patients with PNS was high, and that DPN was alarmingly underdiagnosed in these underserved rural communities. The high prevalence of PNS and underdiagnosis of DPN could influence the development of severe foot complications like diabetic foot ulcer, and even possibly increase the risk of lower extremity amputation in these underserved communities. The at risk population identified by this study would be a resource to help diabetes educators develop targeted education and intervention programs in underserved rural communities.


Epidemiologic evaluation of the risk factors associated with exposure and seroreactivity to Bartonella vinsonii in dogs.
To determine seroprevalence to Bartonella vinsonii subsp berkhoffii in a population of sick dogs from North Carolina and Virginia and to evaluate potential risk factors associated with increased likelihood of exposure to the organism. Serum samples from 1,920 sick dogs. An indirect fluorescent antibody assay was performed on each sample, and the end-point antibody titer was recorded. A case (seropositive) was defined as a dog with reciprocal titer > or = 64, and a control (seronegative) was defined as a dog with reciprocal titer < 16 that was referred within 0 to 3 days of referral of a corresponding case. From this population, 207 dogs (69 cases and 138 controls) were included in a case-control seroepidemiologic study. 3.6% (69/1,920) of the dogs were seropositive to B vinsonii subsp berkhoffii. Results of the case-control study indicated that seropositive dogs were more likely to live in rural environments, frequently on a farm, were free to roam the neighborhood, and were considered to be predominantly outdoor dogs. Moreover, seropositive dogs were 14 times more likely to have a history of heavy tick exposure. After analysis of the case-control study, a more detailed examination of banked sera from dogs with known tick exposure was performed. High correlation was found between sero-reactivity to B vinsonii and seroreactivity to E canis or B canis (36.0 and 57.1%, respectively). Sera derived from dogs experimentally infected with E canis or R rickettsii did not cross react with B vinsonii antigen. Several potential risk factors are associated with canine exposure to B vinsonii. Rhipicephalus sanguineus, the tick vector for E canis and B canis, may be involved in B vinsonii transmission among dogs.


The mitochondrial pathway and reactive oxygen species are critical contributors to interferon-α/β-mediated apoptosis in Ubp43-deficient hematopoietic cells.
UBP43 (also known as USP18) plays a role in the negative regulation of interferon-α/β signaling, and bone marrow cells in Ubp43-deficient mice exhibited hypersensitivity to interferon-α/β-mediated apoptosis. Here, we show that the mitochondrial apoptotic pathway and reactive oxygen species are major contributors to the elevated interferon-α/β-mediated apoptosis in Ubp43-deficient mouse bone marrow cells and in UBP43-knockdown THP-1 cells. Furthermore, TRAIL and FASL, which were proposed as apoptosis inducers upon interferon-α/β treatment in UBP43-knockdown adherent cancer cells, did not cause apoptosis in these hematopoietic cells. Therefore, although UBP43 depletion can cause hypersensitivity to interferon-α/β-mediated apoptosis in a broad range of cell types, the downstream pathway may vary depending on the cell type.


Determination of Cd, Cu, Pb and Zn content of infant formulas by differential pulse anodic stripping voltammetry (DPASV).
The differential pulse anodic stripping voltammetry (DPASV) method described is based on the one reported by Hasse et al., but adapted to normal laboratory conditions. The values obtained in the estimation of the analytical parameters (linearity, detection and quantification limits, precision and accuracy) show that in the conditions described the method is sensitive enough, reliable and useful for determining these elements in infant formulas. A comparison between DPASV and atomic absorption spectroscopy (AAS) methods in the conditions described here shows that the former is less sensitive but that they are similar in precision. The cadmium, copper, lead and zinc contents of different types of infant formulas marketed in Spain are reported.


Sourdough "Biga" Fermentation Improves the Digestibility of Pizza Pinsa Romana: An Investigation through a Simulated Static In Vitro Model.
Baked goods manufacturing parameters and fermentation conditions interfere with the nutrients content and affect their gastrointestinal fate. Pinsa Romana is a type of pizza that, recently, has been commercially rediscovered and that needed elucidation from a nutritional and digestibility perspective. In this study, six types of Pinsa Romana (five made with indirect method and one produced with straight dough technology) were characterized for their biochemical and nutritional features. Several variables like indirect (biga) Pinsa Romana production process, fermentation time and use of sourdough were investigated. The Pinsa Romana made with biga including sourdough and fermented for 48 h at 16 °C ((PR_48(SD)) resulted in the lowest predicted glycemic index, in the highest content of total peptides, total and individual free amino acids and gamma-amino butyric acid (GABA), and in the best protein quality indexes (protein efficiency ratio and nutritional index). The static in vitro digestion showed that the digesta from PR_48(SD) confirmed a reduced in vitro glycemic response after intake, and it showed a lower bioavailability of hydrophilic peptides. Furthermore, the inclusion of sourdough in biga enhanced the bioavailability of protein-related end-products including human health promoting compounds such as essential amino acids.


Mixed Total Variation and L1 Regularization Method for Optical Tomography Based on Radiative Transfer Equation.
Optical tomography is an emerging and important molecular imaging modality. The aim of optical tomography is to reconstruct optical properties of human tissues. In this paper, we focus on reconstructing the absorption coefficient based on the radiative transfer equation (RTE). It is an ill-posed parameter identification problem. Regularization methods have been broadly applied to reconstruct the optical coefficients, such as the total variation (TV) regularization and the L1 regularization. In order to better reconstruct the piecewise constant and sparse coefficient distributions, TV and L1 norms are combined as the regularization. The forward problem is discretized with the discontinuous Galerkin method on the spatial space and the finite element method on the angular space. The minimization problem is solved by a Jacobian-based Levenberg-Marquardt type method which is equipped with a split Bregman algorithms for the L1 regularization. We use the adjoint method to compute the Jacobian matrix which dramatically improves the computation efficiency. By comparing with the other imaging reconstruction methods based on TV and L1 regularizations, the simulation results show the validity and efficiency of the proposed method.


Early histogenesis in human embryonic liver.
The present study reports the results of a light microscopy study on the early histogenesis of human liver. 18 human embryos in the age range of 6 to 10 gestational week were studied. The embryos were provided by the Department of Obstetrics and Gynecology following an abrasion in normal pregnancy. The embryonic liver was studied using conventional histologic technique, histochemical methods for lipids and glycogen detection: by enzyme chemical methods for establishing the activity of the enzymes lactatedehydrogenase (LDH) and succinatedehydrogenase (SDH). The hepatocytes and the basic five types of differentiating cells of mesenchymal origin of the liver were studied: hemopoietic cells, macrophages, endothelial cells, fibroblasts and smooth muscle fibres. Increased activity of the two dehydrogenases and an intensive reaction for glycogen in the hepatocytes and myoblasts were observed; for the other cell types the reaction was distinctly weaker. The obtained data could be associated with the changes in the metabolism of the differentiating cells at the beginning of the hepatoorganogenesis.


Evaluation of leucocytes from sputum samples of pulmonary tuberculosis patients using flow cytometry.
Information about the sputum cells of pulmonary tuberculosis (PTB) patients is scarce. The analysis of sputum cells using optical microscopy (OM) is a well-established method, but it has some serious limitations. To establish a new flow cytometry (FC) protocol for the leucocyte evaluation of sputum samples from PTB patients. A new FC protocol using 0.1% dithiothreitol and 0.5% paraformaldehyde was developed to fluidise sputum samples and kill Mycobacterium tuberculosis, respectively, to allow the analysis of sputum samples collected from TB patients. The protocol was validated by comparing it with OM, and the cellularity of 30 sputum samples from patients with PTB was evaluated. The comparison between leucocyte subsets analysed using OM and FC showed agreement. Immunophenotyping of leucocytes from sputum samples showed that neutrophils (95.7%) comprised the largest proportion of sputum cells, followed by monocytes/macrophages (2.6%) and lymphocytes (1.6%). Among the total T-lymphocytes (100%), 12.3% were T-helper cells, 24.1% were cytotoxic T-cells and 62.9% were gamma/delta T; none of the T lymphocytes had the CD4+/CD8+ phenotype. FC is a useful method for evaluating the different subtypes of leucocytes present in the sputum samples of PTB patients.


[Clinical study of vertical dimension before and after orthodontic treatment in a Class II population].
The authors tried to highlight orthodontics only or mixed "orthopedics + orthodontics" repercussions about vertical dimensions while comparing the measurements before and after treatment done on teleradiographies of profile of 30 hyperdivergent and hypodivergent patients with skeletal class II. The clinical conclusions have been drawn after discussion of the results.


[Schizophrenia concepts in Soviet and Russian psychiatry].
Concepts of schizophrenia of the Soviet Russian school are presented. They are historically based upon the broad concepts of schizophrenia by Kraepelin and Bleuler. The relationships to the German concept of "Einheitspsychose" (unitary psychosis) is emphasized. Along with the discussion of correspondence to and differences with Western diagnostic systems (DSM, ICD) it is pointed out that the old Soviet system of classification extends to psychotic and also non-psychotic forms which in ICD-10 are not attributed to schizophrenia, but to other categories. Differential-diagnostic criteria of sluggish schizophrenia and neurosis, such as positive psychopathological symptoms, thought disturbances and changes in personality, will be delineated. Furthermore, recent developments in Russian psychiatry and modifications in Russian schizophrenia concepts will be exemplified by the concept of "psychic diathesis."


Gummy smile: clinical parameters useful for diagnosis and therapeutical approach.
In the analysis of the characteristics of a pleasant smile, a gummy smile has negative components, which most affect the esthetics of non-verbal communication. For this purpose a proposed classification based upon etiopathogenetic criteria as useful indications for a therapeutical approach is given. The nature of a high smile line can be: dento-gingival, connected to an abnormal dental eruption, which is revealed by a short clinic crown; muscular, caused by an hyperactivity of the elevator muscle of the upper lip; dento-alveolar (skeletal), due to an excessive protuberance or vertical growth of the jawbone (maxillary); lastly, a mixed nature, in the presence of more than one of the above described factors The diagnosis of gummy smile must be precocious and based, with reference to specific parameters, upon a careful analysis of the etiopathogenetic factors and the degree of seriousness of the alteration. A correct treatment plan must contemplate the possibility of an orthognatodontic, orthopedic and/or surgical therapeutic resolution considering the seriousness and complexity of the gums exposures (high smile line) in connection with the age of the subject.


Current status and future prospects of chimeric antigen receptor-T cell therapy in lymphoma research: A bibliometric analysis.
CAR-T cell therapy, a novel therapeutic approach that has attracted much attention in the field of cancer treatment at present, has become the subject of many studies and has shown great potential in the treatment of hematological malignancies, such as leukemia and lymphoma. This study aims to analyze the characteristics of articles published on CAR-T cell therapy in the lymphoma field and explore the existing hotspots and frontiers. The relevant articles published from 2013 to 2022 were retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, Bibliometric online analysis platform, Microsoft Excel, and R software were used for bibliometric analysis and visualization. The number of publications related to the research has been increasing year by year, including 1023 articles and 760 reviews from 62 countries and regions, 2092 institutions, 1040 journals, and 8727 authors. The United States, China, and Germany are the main publishing countries in this research field. The top 10 institutions are all from the United States, the journal with the highest impact factor is BLOOD, the author with the most publications is Frederick L Locke, and the most influential author is Carl H June. The top three keywords are "Lymphoma," "Immunotherapy," and "Therapy." "Maude (2014)" is the most cited and strongest burstiness reference over the past decade. This study provides a comprehensive bibliometric analysis of CAR-T cell therapy in lymphoma, which can help researchers understand the current research hotspots in this field, explore potential research directions, and identify future development trends.


Sexual transmission-risk behaviour among HIV-positive persons: a multisite study using social action theory.
Sexual risk behaviour was explored and described using Social Action Theory. The sexual transmission of HIV is complex and multi-factorial. Social Action Theory provides a framework for viewing self-regulation of modifiable behaviour such as condom use. Condom use is viewed within the context of social interaction and interdependence. Cross-sectional survey. Self-report questionnaire administered to adults living with HIV/AIDS, recruited from clinics, service organizations and by active outreach, between 2010 - 2011. Having multiple sex partners with inconsistent condom use during a 3-month recall period was associated with being male, younger age, having more years of education,substance use frequency and men having sex with men being a mode of acquiring HIV. In addition, lower self-efficacy for condom use scores were associated with having multiple sex partners and inconsistent condom use. Social Action Theory provided a framework for organizing data from an international sample of seropositive persons. Interventions for sexually active, younger, HIV positive men who have sex with men, that strengthen perceived efficacy for condom use, and reduce the frequency of substance use, may contribute to reducing HIV-transmission risk.


Beyond immune thrombocytopenia: the evolving role of thrombopoietin receptor agonists.
Since its discovery, the thrombopoietin (TPO) pathway has been an important pharmaceutical target for the treatment of thrombocytopenia. The first generation of TPO mimetics included peptide agents sharing homology with endogenous TPO, but these introduced a risk of antibody formation to endogenous TPO and were not successful. However, second-generation TPO mimetics or TPO receptor agonists (RAs) are currently being used to treat thrombocytopenia associated with a number of conditions, such as immune thrombocytopenia (ITP), severe aplastic anaemia (SAA), and hepatitis C virus-associated chronic liver disease. Accumulating efficacy and safety data suggest that the role of TPO-RAs in the treatment of thrombocytopenia may evolve in the near future with broader use of these agents in ITP and SAA, as well as approval in other indications, potentially including myelodysplastic syndromes, chemotherapy-associated thrombocytopenia, and post-transplant thrombocytopenia. This review provides an overview of clinical data on the efficacy and safety of TPO-RAs, emphasising recent findings that may expand their clinical utility.


[11 cases of erythema multiforme. The etiological correlations and therapy].
Erythema multiforme (EM) is characterised by a polymorphous eruptive complex which many involve the cutis and oral, genital and conjunctival mucous. Its etiopathogenesis is unclear: it is thought to be associated with various viral or bacterial infective agents (herpes virus, Coxsackie virus, mycoplasmas, etc.), numerous drugs, physical therapy, systemic pathologies of various types. The authors report their experience in relation to 11 patients suffering from EM; the clinical characteristics of each case are reported, together with the course of disease, and the diagnostic and therapeutic protocol adopted. The discussion examines the possible cause of disease: in 5 patients the etiology was traced back to viral infections (4 herpes and 1 coxsackie) and to the administration of drugs in the remaining cases (4 in relation to anti-phlogistic agents and 2 regarding antibiotics).


Daily supplementation with mushroom (Agaricus bisporus) improves balance and working memory in aged rats.
Decline in brain function during normal aging is partly due to the long-term effects of oxidative stress and inflammation. Several fruits and vegetables have been shown to possess antioxidant and anti-inflammatory properties. The present study investigated the effects of dietary mushroom intervention on mobility and memory in aged Fischer 344 rats. We hypothesized that daily supplementation of mushroom would have beneficial effects on behavioral outcomes in a dose-dependent manner. Rats were randomly assigned to receive a diet containing either 0%, 0.5%, 1%, 2%, or 5% lyophilized white button mushroom (Agaricus bisporus); after 8 weeks on the diet, a battery of behavioral tasks was given to assess balance, coordination, and cognition. Rats on the 2% or 5% mushroom-supplemented diet consumed more food, without gaining weight, than rats in the other diet groups. Rats in the 0.5% and 1% group stayed on a narrow beam longer, indicating an improvement in balance. Only rats on the 0.5% mushroom diet showed improved performance in a working memory version of the Morris water maze. When taken together, the most effective mushroom dose that produced improvements in both balance and working memory was 0.5%, equivalent to about 1.5 ounces of fresh mushrooms for humans. Therefore, the results suggest that the inclusion of mushroom in the daily diet may have beneficial effects on age-related deficits in cognitive and motor function.


Empirical comparison of subgroup effects in conventional and individual patient data meta-analyses.
Individual patient data (IPD) meta-analyses have been proposed as a major improvement in meta-analytic methods to study subgroup effects. Subgroup effects of conventional and IPD meta-analyses using identical data have not been compared. Our objective is to compare such subgroup effects using the data of six trials (n = 1,643) on the effectiveness of antibiotics in children with acute otitis media (AOM). Effects (relative risks, risk differences [RD], and their confidence intervals [CI]) of antibiotics in subgroups of children with AOM resulting from (i) conventional meta-analysis using summary statistics derived from published data (CMA), (ii) two-stage approach to IPD meta-analysis using summary statistics derived from IPD (IPDMA-2), and (iii) one-stage approach to IPD meta-analysis where IPD is pooled into a single data set (IPDMA-1) were compared. In the conventional meta-analysis, only two of the six studies were included, because only these reported on relevant subgroup effects. The conventional meta-analysis showed larger (age < 2 years) or smaller (age > or = 2 years) subgroup effects and wider CIs than both IPD meta-analyses (age < 2 years: RDCMA -21 percent, RDIPDMA-1 -16 percent, RDIPDMA-2 -15 percent; age > or =2 years: RDCMA -5 percent, RDIPDMA-1 -11 percent, RDIPDMA-2 -11 percent). The most important reason for these discrepant results is that the two studies included in the conventional meta-analysis reported outcomes that were different both from each other and from the IPD meta-analyses. This empirical example shows that conventional meta-analyses do not allow proper subgroup analyses, whereas IPD meta-analyses produce more accurate subgroup effects. We also found no differences between the one- and two-stage meta-analytic approaches.


Erythema nodosum and conjunctivitis triggered by enteritis due to Salmonella typhimurium.
We describe a patient, a 59-year-old woman, who developed erythema nodosum and conjunctivitis after enteritis due to Salmonella typhimurium. The patient was HLA-B27 negative and had circulating immune complexes, as determined by the conglutinin-binding enzyme immunoassay. Immunopathogenesis of the extraintestinal findings is discussed.


Clinical learning environment and supervision: experiences of Norwegian nursing students - a questionnaire survey.
To measure nursing students' experiences and satisfaction with their clinical learning environments. The primary interest was to compare the results between students with respect to clinical practice in nursing homes and hospital wards. Clinical learning environments are important for the learning processes of nursing students and for preferences for future workplaces. Working with older people is the least preferred area of practice among nursing students in Norway. A cross-sectional design. A validated questionnaire was distributed to all nursing students from five non-randomly selected university colleges in Norway. A total of 511 nursing students completed a Norwegian version of the questionnaire, Clinical Learning Environment, Supervision and Nurse Teacher (CLES+T) evaluation scale in 2009. Data including descriptive statistics were analysed using the Statistical Program for the Social Sciences. Factor structure was analysed by principal component analysis. Differences across sub-groups were tested with chi-square tests and Mann-Whitney U test for categorical variables and t-tests for continuous variables. Ordinal logistic regression analysis of perceptions of the ward as a good learning environment was performed with supervisory relationships and institutional contexts as independent variables, controlling for age, sex and study year. The participating nursing students with clinical placements in nursing homes assessed their clinical learning environment significantly more negatively than those with hospital placements on nearby all sub-dimensions. The evidence found in this study indicates that measures should be taken to strengthen nursing homes as learning environments for nursing students. To recruit more graduated nurses to work in nursing homes, actions to improve the learning environment are needed.


Exciton-phonon scattering and nonradiative relaxation of excited carriers in hydrothermally synthesized CdTe quantum dots.
Naturally formed CdTe/CdS core/shell quantum dot (QD) structures in the presence of surface stabilizing agents have been synthesized by a hydrothermal method. Size and temperature dependent photoluminescence (PL) spectra have been investigated to understand the exciton-phonon interaction, and radiative and nonradiative relaxation of carriers in these QDs. The PL of these aqueous CdTe QDs (3.0-4.8 nm) has been studied in the temperature range 15-300 K. The strength of the exciton-LO-phonon coupling, as reflected in the Huang-Rhys parameter 'S' is found to increase from 1.13 to 1.51 with the QD size varying from 4.8 to 3.0 nm. The PL linewidth (FWHM) increases with increase in temperature and is found to have a maximum in the case of QDs of 3.0 nm in size, where the exciton-acoustic phonon coupling coefficient is enhanced to 51 μeV K(-1), compared to the bulk value of 0.72 μeV K(-1). To understand the nonradiative processes, which affect the relaxation of carriers, the integrated PL intensity is observed as a function of temperature. The integrated PL intensity remains constant until 50 K for relatively large QDs (3.9-4.8 nm) beyond which a thermally activated process takes over. Below 150 K, a small activation energy, 45-19 meV, is found to be responsible for the quenching of the PL. Above 150 K, the thermal escape from the dot assisted by scattering with multiple longitudinal optical (LO) phonons is the main mechanism for the fast quenching of the PL. Besides this high temperature quenching, interestingly for relatively smaller size QDs (3.4-3.0 nm), the PL intensity enhances as the temperature increases up to 90-130 K, which is attributed to the emission of carriers from interface/trap states having an activation energy in the range of 6-13 meV.


Meta-Analysis of Serum Gastrin-Releasing Peptide Precursor as a Biomarker for Diagnosis of Small Cell Lung Cancer
Background: The serum level of gastrin-releasing peptide precursor (proGRP) is generally. elevated in patients with small cell lung cancer (SCLC). However, the diagnostic sensitivity and specificity of serum proGRP in SCLC cases remains controversial. The study aimed to assess the diagnostic value of this biomarker by meta-analysis. Materials and Methods: The Cochrane, Clinical trials, Pubmed, Web of Science and Embase databases were searched and diagnostic values were calculated or extracted. Statistical analysis was accomplished with RevMan 5.3 and STATA 12.0 software. Results: A total of 27 studies with 7268 participants were included. The pooled sensitivity, specificity, PLR, NLR and DOR were 0.754 (95% CI: 0.700-0.802), 0.945 (95% CI: 0.916-0.965), 13.804 (95% CI: 9.096-20.948), 0.260 (95% CI: 0.213-0.317) and 53.101 (95% CI: 34.327-82.145) respectively. The AUC was 0.910 (95% CI: 0.880-0.930). Significant publication bias was not found (P =0.622). Conclusions: The meta-analysis indicated that serum proGRP is indeed a useful biomarker with good sensitivity and high specificity for diagnosis of SCLC. Therefore proGRP can be expected to be widely applied in the clinic for identification of lung cancer patients.


Semipolar (202̅1̅) GaN and InGaN Light-Emitting Diodes Grown on Sapphire.
We have demonstrated growing uniform and purely nitrogen polar semipolar (202̅1̅) GaN epilayers on 2 in. patterned sapphire substrates. The as-grown surface of (202̅1̅) GaN is composed of two stable facets: (101̅0) and (101̅1̅). A chemical mechanical polishing process was further used to planarize the surface with a final surface root-mean-square roughness of less than 1.5 nm over an area of 10 × 10 μm2. InGaN light-emitting diodes were grown on a polished (202̅1̅) GaN/sapphire template with an electroluminescence emission at around 490 nm. Our work exhibits the potential to produce high-quality nitrogen-polar semipolar GaN templates and optoelectronic devices on large-area sapphire substrates with economical feasibility.


A Rare Association of Hepatitis A Virus Infection with Type-1 Diabetes.
Patients with type-1 diabetes are predisposed to develop a spectrum of liver diseases, which includes fatty liver, steatohepatitis and cirrhosis. The association of hepatitis A infection with type-1 diabetes is extremely rare. To the best of our knowledge, our case is the first case report in children. We described a nine year-old girl who had type-1 diabetes and developed hepatitis A virus infection without complications. A review of the literature is also provided.


Atrial function after surgical and percutaneous closure of atrial septal defect: a strain rate imaging study.
The effect of operation and the effect of the imposition of an occluding device on atrial function for patients with an atrial septal defect (ASD) has never been studied. Thus, the aim of this study was to evaluate for the first time both left atrial (LA) and right atrial (RA) function of children after transcatheter ASD closure with that of sex- and age-matched patients with surgically treated ASD, and sex- and age-matched control subjects using strain (epsilon) and epsilon rate imaging (SR). In all, 45 participants formed our studied sample: 15 patients after successful ASD device closure (ASD-D [atrial septal defect device closure] group, mean age: 9 +/- 3 years) and 15 age- and sex-matched patients after successful ASD surgical closure (ASD-S [atrial septal defect surgical closure] group, mean age: 9 +/- 3 years). All patients underwent ASD correction at least 6 months before the study. As a control group we selected 15 age- and sex-matched control subjects. In the ASD-S group the peak systolic epsilon and SR values were significantly reduced in both RA and LA when compared with control and ASD-D groups (P < .01). In the ASD-D group there was no significant difference in both LA and RA deformation properties when compared with control subjects. SR imaging indexes could provide new, noninvasive, clinically relevant insight on regional changes in atrial function for patients with ASD. ASD percutaneous closure is useful not only because it is less expensive and invasive than open-heart operation but also for its conservation of both LA and RA regional myocardial properties.


1-(2-Methyl-5-phenyl-3-thienyl)-2-(3-methyl-5-phenyl-2-thienyl)-3,3,4,4,5,5-hexafluorocyclopent-1-ene: a novel photochromic hybrid diarylethene.
The title compound, C27H18F6S2, a novel photochromic hybrid diarylethene derivative containing 2- and 3-thienyl substituents, is one of the most promising photochromic candidates with shorter wavelength for optical storage and other optoelectronic devices. In the crystal structure, the molecule adopts a photoactive antiparallel conformation. The distance between the two reactive C atoms, i.e. the ring C atoms to which the methyl groups are attached, is 3.430 (4) A. The dihedral angles between the thienyl and adjacent phenyl rings are 26.8 (2) and 33.98 (9) degrees.


Green complexity, economic fitness, and environmental degradation: evidence from US state-level data.
Green production is one of the major debates as environmental degradation poses threats globally. The paper attempts to explore the relationship between green production and environmental quality by using Economic Fitness approach. We develop a Green Complexity Index (GCI) dataset consisting of 290 traded green-labeled products and Economic Fitness Index (EFI) for the US states between 2002 and 2018. We analyze the environmental performance of green production using the GCI and EFI data at the sub-national level. Findings indicate that exporting more complex green products has insignificant effects on local (i.e., sulfur dioxide, particulate Matter 10) and global polluters such as carbon dioxide, even accounting for per capita income. Yet, economic fitness has a significant negative impact on the emission levels implying that sophisticated production significantly improves environmental quality in the USA. The insignificant impact of GCI on environmental degradation suggests that green product classifications should incorporate the production and end-use stages of goods to limit the adverse environmental effects of green-labeled products.


Intraoperative Dilemmas in Polyorchidism: To Pex or not to Pex!!
Supernumerary testis or polyorchidism is a rare congenital anomaly. It is often associated with processus vaginalis anomalies and with increased risk of malignancy and infertility. The approach to management has changed over time, with improvements in imaging techniques allowing surveillance to replace surgical excision or exploration and biopsy. In this study, two patients were managed with orchidopexy and have had a close follow-up of 2 years.


Competitive effects of verapamil and calcium ion as regulators of myocardial enzyme leakage.
Verapamil (Vp) has been found to augment the creatine kinase (CK) and lactate dehydrogenase (LDH) leakage from isolated mouse heart incubated in vitro at 25 degrees C. This leakage was concentration-dependent, and in the second hour followed the Henri-Michaelis-Menten kinetics model. Least-squares estimates obtained with this model for the Km values of verapamil were 0.38 +/- 0.16 mM (CK leakage) and 0.51 +/- 0.21 mM (LDH leakage). Calcium ion inhibited this effect of verapamil, completely abolishing it when the [Ca2+]:[Vp] greater than or equal to 2. At lower [Ca2+], the effect of verapamil also followed hyperbolic kinetics; the Km of verapamil was increased, but the asymptomatic leakage rate at high [Vp] was not changed significantly. These features indicate that the calcium ion is a competitive inhibitor of verapamil-augmented enzyme leakage. These observations suggest that there may exist a common calcium ion and verapamil binding site, or two allosterically related binding sites, which represent a prime determinant of myocardial leakage. The concept of a vulnerable site that binds calcium ions and verapamil competitively and initiates or vitiates processes that influence myocardial enzyme leakage is attractive because it suggests new approaches to the problem of myocardial preservation. As verapamil is thought not to enter the cell, the site of the competitive inhibition may be the sarcolemmal coat.


Computation of Förster Resonance Energy Transfer in Lipid Bilayer Membranes.
Calculations of Förster Resonance Energy Transfer (FRET) often neglect the influence of different chromophore orientations or changes in the spectral overlap. In this work, we present two computational approaches to estimate the energy transfer rate between chromophores embedded in lipid bilayer membranes. In the first approach, we assess the transition dipole moments and the spectral overlap by means of quantum chemical calculations in implicit solvation, and we investigate the alignment and distance between the chromophores in classical molecular dynamics simulations. In the second, all properties are evaluated integrally with hybrid quantum mechanical/molecular mechanics (QM/MM) calculations. Both approaches come with advantages and drawbacks, and despite the fact that they do not agree quantitatively, they provide complementary insights on the different factors that influence the FRET rate. We hope that these models can be used as a basis to optimize energy transfers in nonisotropic media.


Effect of suckling on serum follicle-stimulating hormone and luteinizing hormone in nursing women.
The effect of breast feeding on serum FSH and LH concentrations was studied in 13 puerperal women. Despite the collateral increase in serum prolactin levels, nursing was not followed by significant changes in serum FSH or LH levels during a 30-min observation period. Our data indicate that nursing has no significant effect on pituitary FSH and LH release.


Patient-Controlled Analgesia Following Lumbar Spinal Fusion Surgery Is Associated With Increased Opioid Consumption and Opioid-Related Adverse Events.
Optimal postoperative pain control is critical after spinal fusion surgery. There remains significant variability in the use of postoperative intravenous opioid patient-controlled analgesia (PCA) and few data evaluating its utility compared with nurse-controlled analgesia (NCA) among patients with lumbar fusion. To investigate the efficacy of postoperative PCA compared with NCA to improve opiate prescription practices. A retrospective review from a single institution was conducted in consecutive patients treated with posterior lumbar spinal fusion for degenerative pathology. Patients were divided into cohorts on the basis of postoperative treatment with PCA or NCA. Postoperative pain scores, length of stay, and total opioid consumption data were collected. Patients were stratified according to preoperative opioid consumption as opioid naive (0 morphine milligram equivalents [MME] daily), low consumption (1-60 MME), high consumption (61-90 MME), or very high consumption (>90 MME). A total of 240 patients were identified, including 62 in the PCA group and 178 in the NCA group. PCA patients had higher mean preoperative opioid consumption than NCA patients (49.2 vs 24.3 MME, P = .009). PCA patients had higher mean opioid consumption in the first 72 h in all 4 of the preoperative opioid consumption subcategories. Pain control and adverse event rates were similar between PCA and NCA in the low to high preoperative opioid consumption groups. Postoperative PCA is associated with significantly more opioid consumption in the first 72 h after surgery and equal or worse postoperative pain scores compared with NCA after lumbar spinal fusion surgery.


Detection of doxorubicin cardiotoxicity in patients with sarcomas by indium-111-antimyosin monoclonal antibody studies.
To assess myocardial cell damage due to doxorubicin cardiotoxicity, we prospectively studied 30 patients with sarcomas who were receiving chemotherapy, including doxorubicin. Sixteen patients were treated by continuous infusion over 72 hr and 14 patients were treated by bolus injection. Antimyosin studies and left ventricular ejection fraction (LVEF) measurements were performed before chemotherapy and at intermediate and maximal cumulative doses. Myocardial antimyosin uptake was quantified by a heart-to-lung ratio (HLR). Myocardial antimyosin uptake was observed in all patients at 240-300 mg/m2 when ejection fraction was still maintained. Seven patients presented with a decrease of > or = 10% in absolute ejection fraction units at 420-600 mg/m2. Five of these patients had mild congestive heart failure. All patients who presented with a decrease in LVEF > or = 10% at 420-600 mg/m2 had increased antimyosin uptake with HLR > or = 1.90 at a cumulative dose of 240-300 mg/m2. Patients who were treated with continuous infusion had less antimyosin uptake than those who were treated with bolus administration (mean HLR of 1.70 +/- 0.09 versus HLR of 2.01 +/- 0.16 at a cumulative dose of 240-300 mg/m2, p < 0.01; HLR of 1.86 +/- 0.12 versus HLR of 2.32 +/- 0.34 at a cumulative dose of 420-600 mg/m2, p < 0.01). Two of 16 patients treated by continuous infusion and 5 of 14 patients treated by bolus injection presented with a decrease in ejection fraction > or = 10%. LVEF after chemotherapy in the infusion group was 56% +/- 5% and 48% +/- 8% (p < 0.05) in the bolus group. Antimyosin studies are helpful in the assessment of doxorubicin cardiotoxicity. Intense antimyosin uptake at intermediate cumulative doses identifies patients at risk of cardiotoxicity before ejection fraction deteriorates. Patients with sarcomas treated by continuous infusion present with less antimyosin uptake than those treated with bolus injection, indicating less severe cardiotoxicity.


Atomoxetine for hyperactivity in autism spectrum disorders: placebo-controlled crossover pilot trial.
To explore placebo-controlled efficacy and safety of atomoxetine (ATX) for attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorders (ASD). Children ages 5 to 15 with ASD and prominent ADHD symptoms were randomly assigned to order in a crossover of clinically titrated ATX and placebo, 6 weeks each, separated by 1-week washout. Slopes for each condition were compared by paired t test. In 2004-2005, 12 boys and 4 girls (7 with autistic disorder, 1 Asperger's, 8 pervasive developmental disorder not otherwise specified) all completed at least 3 weeks of each condition. On the primary outcome, the Hyperactivity subscale of the Aberrant Behavior Checklist, ATX was superior to placebo (p =.043, effect size d = 0.90). It was also superior on a 0 to 3 rating of nine DSM-IV ADHD hyperactive/impulsive symptoms (p =.005, d = 1.27), but missed significance on nine inattentive symptoms (p =.053, d= 0.89). Nine subjects responded to ATX, four to placebo (25% improvement on the Hyperactivity subscale plus Clinical Global Impressions-Improvement of 1-2. One was rehospitalized for recurrent violence on ATX. Adverse events were otherwise tolerable, with no tendency to stereotypy. ATX appears safe and effective for treating hyperactivity in some children with autism spectrum disorders. The effect appears as large as in a multisite methylphenidate trial in the same population, with fewer intolerable side effects. Further study in autism spectrum disorders is indicated.


A modified version of the Drug Abuse Screening Test among undergraduate students.
The present study assesses the prevalence of items from a modified version of the Drug Abuse Screening Test, Short Form (DAST-10) for substances other than alcohol among undergraduate students. More than 4,500 undergraduate students at a large Midwestern research university completed a web-based survey in 2005. Nearly 1 every 10 undergraduate students experienced three or more DAST-10 items in the past 12 months. Although the prevalence of illicit drug use did not differ by gender, undergraduate men were significantly more likely than women to report DAST-10 items. Less than 6% of individuals who reported three or more drug DAST-10 items had ever used treatment services for substance use. As a brief screening instrument, the DAST-10 offers promise for detecting possible drug abuse among college students. Based on the prevalence of drug use, colleges and universities are encouraged to provide screening opportunities to identify and to provide services for students at high risk for drug abuse.