Pixel-wise estimation of noise statistics on iterative CT reconstruction from a single scan.
As iterative CT reconstruction continues to advance, the spatial distribution of noise standard deviation (STD) and accurate noise power spectrum (NPS) on the reconstructed CT images become important for method evaluation as well as optimization of algorithm parameters. Using a single CT scan, we propose a practical method for pixel-wise calculation of noise statistics on an iteratively reconstructed CT image, which enables accurate calculation of noise STD for each pixel and NPS. We first derive the noise propagation from measured projections to an iteratively reconstructed CT image provided that the projection noise is known. We then show that the model of noise propagation remains approximately unchanged for extra simulated noise added on the measured projections. To compute the noise STD map and the NPS map on an iteratively reconstructed CT image from a single scan, we first iteratively reconstruct the CT image from the measured projections using an existing reconstruction algorithm. The same measured projections are added by different sets (a total of 32 sets in our implementation) of projection noise simulated from an estimated projection noise model, and are then used to iteratively reconstruct different CT images. The calculations of the noise STD map and the NPS map are finally performed on the entire stack of these different reconstruction images. We evaluate our method on an anthropomorphic head phantom, and demonstrate the clinical utility on a set of head and neck patient CT data, using two iterative CT reconstruction algorithms: the penalized weighted least-square (PWLS) algorithm and the total-variation (TV) regularization. In the head phantom case, repeated scans are acquired to generate the ground truths of noise STD and NPS maps. Using only one single scan, the proposed method accurately calculates the noise STD maps with a root-mean-square error (RMSE) of less than 5HU. In the NPS map estimation, we compare the result of our proposed method with that of the conventional method which calculates the NPS maps on a uniform region of interest on one CT image. Our method outperforms the conventional method on the NPS map estimation with RMSE reduced by 92%. The implementation of the proposed method on the patient data successfully provides the noise STD values around complex structures and a high-quality NPS map. The proposed method accurately calculates noise STD for each pixel and NPS on an iteratively reconstructed CT image, with no requirement of repeated CT scans. It provides a detailed evaluation of imaging performance of different iterative reconstruction methods on the same CT dataset.


Curcumin effect on cancer cells' multidrug resistance: An update.
Chemotherapy is one of the main methods for cancer treatment. However, despite many advances in the design of anticancer drugs, their efficiency is limited due to their high toxicity and resistance of cells to chemotherapeutic drugs. In order to improve the cancer therapy, it is essential to use the compounds that can overcome drug resistance and increase treatment efficiency. Researchers have studied the effects of natural compounds for the controlling various drug resistance mechanisms. Curcumin is a natural phenolic compound which shows potent anticancer activities in different tumors, alone or as an adjuvant with other antitumor drugs to prevent or inhibit the survival and cancer progression by various mechanisms. The role of curcumin in overcoming drug resistance was followed by reviewing different applications of curcumin in cancer therapy. Afterward, the clinical impacts of curcumin, role of curcumin in decreasing drug resistance in different cancer cells and its mechanisms were discussed. It has been demonstrated that curcumin regulates signaling pathways in cancer cells, reduces the expression of proteins related to drug resistance, and increases the performance of antitumor drugs at various levels. Curcumin reverses multidrug resistance mechanisms and increases sensitivity of resistance cells to chemotherapy. This review mainly focuses on different mechanisms of drug resistance and curcumin as a nontoxic natural substance to eliminate the effects of drug resistance through modulation and controlling cell resistance pathways and eventually suggests curcumin as a potent chemosensitizer in cancers.


Mms21: A Putative SUMO E3 Ligase in Candida albicans That Negatively Regulates Invasiveness and Filamentation, and Is Required for the Genotoxic and Cellular Stress Response.
In the life cycle of the fungal pathogen Candida albicans, the formation of filamentous cells is a differentiation process that is critically involved in host tissue invasion, and in adaptation to host cell and environmental stresses. Here, we have used the Gene Replacement And Conditional Expression library to identify genes controlling invasiveness and filamentation; conditional repression of the library revealed 69 mutants that triggered these processes. Intriguingly, the genes encoding the small ubiquitin-like modifier (SUMO) E3 ligase Mms21, and all other tested members of the sumoylation pathway, were both nonessential and capable of triggering filamentation upon repression, suggesting an important role for sumoylation in controlling filamentation in C. albicans We have investigated Mms21 in detail. Both Mms21 nulls (mms21Δ/Δ) and SP [Siz/Pias (protein inhibitor of activated signal transducer and activator of transcription)] domain (SUMO E3 ligase domain)-deleted mutants displayed invasiveness, filamentation, and abnormal nuclear segregation; filament formation occurred even in the absence of the hyphal transcription factor Efg1. Transcriptional analysis of mms21Δ/Δ showed an increase in expression from two- to eightfold above that of the wild-type for hyphal-specific genes, including ECE1, PGA13, PGA26, HWP1, ALS1, ALS3, SOD4, SOD5, UME6, and HGC1 The Mms21-deleted mutants were unable to recover from DNA-damaging agents like methyl methane sulfonate, hydroxyurea, hydrogen peroxide, and UV radiation, suggesting that the protein is important for genotoxic stress responses. In addition, the mms21Δ/Δ mutant displayed sensitivity to cell wall and thermal stresses, and to different antifungal drugs. All these findings suggest that Mms21 plays important roles in cellular differentiation, DNA damage and cellular stress responses, and in response to antifungal drugs.


Illusions can warp visual space.
Our perception of the space around us is not veridical. It has been reported that the systematic errors in our perception of visual space can be described by a reasonably well-behaving space (the resulting space is approximately projective and complies with an affine geometry). The evidence for this is that the perceived centre of a set of points is independent of the order of the steps taken to construct it. We investigated whether this is also the case in displays with well-known 2-D visual illusions. In two examples (Judd and Poggendorff illusions), we show that the perceptual centre of a set of points depends on how this centre is constructed. The misperceptions induced by visual illusions are thus of a different nature than our everyday misperceptions. We argue that the concept of perceived visual space is not very useful for describing human behaviour. We propose an alternative description whereby illusions do not deform a visual space, but only a single visual attribute, leaving other attributes unaffected.


Early postnatal growth of preterm low birth weight, appropriately-sized infants.
Postnatal growth monitoring is useful in assessing the health ofpreterm babies but their growth patterns have not been sufficiently studied in Africans. To describe the growth achievements ofpreterm, low birth weight, appropriately-sized, Nigerian infants. The subjects were prospectively recruited from two centers Olabisi Onabanjo University Teaching Hospital (January 1994 to June 1995) and Havana Specialist Hospital (June 1995 to June 1997). The weight, length and occipito-frontal circumference of 89 preterm, low birth weight, appropriate-for-dates infants were monitored from birth until 53 post-conceptual weeks. Growth velocities were compared with 46 term infants. Initial weight loss, age at regaining birth weight and growth rate in the early postnatal weeks were inversely related to gestational age. Subsequent weight gain was directly related to gestational age. Between birth and 40 weeks post conception, growth rates for different gestational age groups were 129 to 207 g/week (weight), 0.78 to 0.93 cm/week (length) and 0.62 to 0.65 cm/week (head circumference). After 40 weeks, the corresponding rates were 188 to 238 g/week, 0.86 to 0.96 cm week and 0.48 to 0.50 cm/week, respectively. Head growth demonstrated a faster catch-up than weight and body length in that order. The observed growth rates were slower in some respects than Caucasian figures but faster than reported for the Japanese. Study subjects had growth patterns within previously defined ranges. The better profile of western babies is probably related to better infrastructure while the advantage over Asian babies is probably racial.


Cytogenetic profile of Down syndrome in Alexandria, Egypt.
During 1992-2001, 673 Down syndrome patients were referred to the Department of Human Genetics in Alexandria. Regular (free) trisomy 21 constituted 95.4% of cases; Robertsonian translocation 2.7%; and mosaicism 0.7%. In 8 cases, regular trisomy 21 was associated with structural or numerical chromosome anomalies. Translocation was parentally inherited for 33.3% of cases and maternal transmission was twice as common as paternal. Two translocated Down syndrome fetuses were diagnosed prenatally in a t(14;21) carrier mother. Mean maternal age was high in regular trisomy 21 (38.2 years) but not in translocation (25.3 years). There was an excess of males in all groups except the mosaic group where the male:female ratio was 0.67. Cytogenetic investigations assist in patient management and family counselling.


Membranar effects exerted in vitro by polyphenols - quercetin, epigallocatechin gallate and curcumin - on HUVEC and Jurkat cells, relevant for diabetes mellitus.
Polyphenols are largely studied for their beneficial action in various pathologies, but the correlation with their effects on cell membranes is still elusive. In the present study we assessed the effects exerted in vitro by quercetin, epigallocatechin gallate and curcumin on membrane fluidity and transmembrane potential of human umbilical vein endothelial cells and Jurkat T lymphoblasts, in experimental conditions mimicking diabetes mellitus, i.e. high glucose conditions or increased concentration of advanced glycation end products. Results showed that the investigated polyphenols had beneficial effects on cell membranes altered in diabetic conditions, by restoring transmembrane potential and by membrane "stiffening". Moreover, they limited the release of pro-inflammatory factors, like monocyte chemotactic protein-1. These effects were more obvious for cells exposed to advanced glycation end products specific for the late stages of diabetes. Apparently, the inhibitory action of polyphenols on lipid peroxidation was associated with a decrease of membrane fluidity. Concluding, our in vitro study highlighted the potential beneficial action of polyphenols mainly in the late stages of diabetes, exerted at the level of membrane fluidity and transmembrane potential, accompanied by an anti-inflammatory effect on endothelial and immune cells.


Long-term analysis of biologic and technical aspects of fixed partial dentures with cantilevers.
The aim of the present clinical study was to analyze the long-term treatment outcome of fixed partial dentures (FPD) with cantilevers. Ninety-two patients with 115 cantilever FPDs on 239 abutment teeth were examined. Immediately following cementation, radiographs of the abutment teeth were obtained. At the follow-up examination 5 to 16 years after cementation, the abutment teeth were clinically and radiographically evaluated. Besides the assessment of periodontal parameters and vitality testing, the presence of carious lesions of the abutment teeth, loss of retention, fracture of bridgework, and fracture of abutment teeth were also recorded. The Student's t test was used to detect differences between abutment teeth and control teeth with natural crowns as well as over time within the groups. Plaque scores and bleeding on probing were low at both abutment and nonabutment teeth. Mean probing pocket depth and level of the clinical attachment never exceeded 3.0 mm in both groups. The radiographic bone levels at abutments were stable within 3% over the observation period. Of the 120 initially vital abutment teeth, 12 (10%) lost vitality during the observation period; one (1%) of the 119 initially nonvital abutments showed periapical pathology. Development of secondary caries was observed at 8% of the 239 abutment teeth. In total, 8% of the abutment teeth were affected by loss of retention, which made up more than half of all technical problems. Material fractures only occurred occasionally, affecting from 1% to less than 3% of the abutment teeth. Fracture of abutment teeth amounted to 3% and was twice as frequent at abutments adjacent to cantilevers compared to abutments not adjacent to cantilevers. The most frequent biologic (caries) and technical complications (loss of retention) made up more than half of all problems recorded. These problems may be at least partially avoided by performing optimal plaque control and by strictly observing the rules for preparation of retentive FPD abutments.


A sequence-based genetic map of Medicago truncatula and comparison of marker colinearity with M. sativa.
A core genetic map of the legume Medicago truncatula has been established by analyzing the segregation of 288 sequence-characterized genetic markers in an F(2) population composed of 93 individuals. These molecular markers correspond to 141 ESTs, 80 BAC end sequence tags, and 67 resistance gene analogs, covering 513 cM. In the case of EST-based markers we used an intron-targeted marker strategy with primers designed to anneal in conserved exon regions and to amplify across intron regions. Polymorphisms were significantly more frequent in intron vs. exon regions, thus providing an efficient mechanism to map transcribed genes. Genetic and cytogenetic analysis produced eight well-resolved linkage groups, which have been previously correlated with eight chromosomes by means of FISH with mapped BAC clones. We anticipated that mapping of conserved coding regions would have utility for comparative mapping among legumes; thus 60 of the EST-based primer pairs were designed to amplify orthologous sequences across a range of legume species. As an initial test of this strategy, we used primers designed against M. truncatula exon sequences to rapidly map genes in M. sativa. The resulting comparative map, which includes 68 bridging markers, indicates that the two Medicago genomes are highly similar and establishes the basis for a Medicago composite map.


Data processing system for the centre of nutrition and metabolic diseases.
The paper is devoted to the functional specification and the architecture of a data processing system to database generation and management within the Centre of Nutrition and Metabolic Diseases in Bucharest. The main operations performed by the system refer to: -Patient admission. A patient file which is created for any new patient, contains all the details hitherto included in the patient registration form. -File update, carried out periodically or whenever required. Any new relevant detail is added to the existing file in a conversational manner. -Report generation. The reports are produced periodically or upon request. -Inventory and stock control concerning the drugs dispensed free of charge. -Data processing and classification. -Creation and retrieval of patient archives. -Display on request of the various details contained by the patient file. The described system can be implemented on an INDEPENDENT 1-100 general purpose minicomputer, having a main memory of 96 words. The disc-based AMS operating system is used. The system operates in real time, although off-line background jobs can be run in order to assist the scientific work. A FORTRAN compiler is part of the operating system.


Lipopolysacharide Rapidly and Completely Suppresses AgRP Neuron-Mediated Food Intake in Male Mice.
Although Agouti-related peptide (AgRP) neurons play a key role in the regulation of food intake, their contribution to the anorexia caused by proinflammatory insults has yet to be identified. Using a combination of neuroanatomical and pharmacogenetics experiments, this study sought to investigate the importance of AgRP neurons and downstream targets in the anorexia caused by the peripheral administration of a moderate dose of lipopolysaccharide (LPS) (100 μg/kg, ip). First, in the C57/Bl6 mouse, we demonstrated that LPS induced c-fos in select AgRP-innervated brain sites involved in feeding but not in any arcuate proopiomelanocortin neurons. Double immunohistochemistry further showed that LPS selectively induced c-Fos in a large subset of melanocortin 4 receptor-expressing neurons in the lateral parabrachial nucleus. Secondly, we used pharmacogenetics to stimulate the activity of AgRP neurons during the course of LPS-induced anorexia. In AgRP-Cre mice expressing the designer receptor hM3Dq-Gq only in AgRP neurons, the administration of the designer drug clozapine-N-oxide (CNO) induced robust food intake. Strikingly, CNO-mediated food intake was rapidly and completely blunted by the coadministration of LPS. Neuroanatomical experiments further indicated that LPS did not interfere with the ability of CNO to stimulate c-Fos in AgRP neurons. In summary, our findings combined together support the view that the stimulation of select AgRP-innervated brain sites and target neurons, rather than the inhibition of AgRP neurons themselves, is likely to contribute to the rapid suppression of food intake observed during acute bacterial endotoxemia.


Silencing of long noncoding RNA AK139328 attenuates ischemia/reperfusion injury in mouse livers.
Recently, increasing evidences had suggested that long noncoding RNAs (LncRNAs) are involved in a wide range of physiological and pathophysiological processes. Here we determined the LncRNA expression profile using microarray technology in mouse livers after ischemia/reperfusion treatment. Seventy one LncRNAs were upregulated, and 27 LncRNAs were downregulated in ischemia/reperfusion-treated mouse livers. Eleven of the most significantly deregulated LncRNAs were further validated by quantitative PCR assays. Among the upregulated LncRNAs confirmed by quantitative PCR assays, AK139328 exhibited the highest expression level in normal mouse livers. siRNA-mediated knockdown of hepatic AK139328 decreased plasma aminotransferase activities, and reduced necrosis area in the livers with a decrease in caspase-3 activation after ischemia/reperfusion treatment. In ischemia/reperfusion liver, knockdown of AK139328 increased survival signaling proteins including phosphorylated Akt (pAkt), glycogen synthase kinase 3 (pGSK3) and endothelial nitric oxide synthase (peNOS). Furthermore, knockdown of AK139328 also reduced macrophage infitration and inhibited NF-κB activity and inflammatory cytokines expression. In conclusion, these findings revealed that deregulated LncRNAs are involved in liver ischemia/reperfusion injury. Silencing of AK139328 ameliorated ischemia/reperfusion injury in the liver with the activation of Akt signaling pathway and inhibition of NF-κB activity. LncRNA AK139328 might be a novel target for diagnosis and treatment of liver surgery or transplantation.


Improved procedure for lecithin/sphingomyelin ratio in amniotic fluid reduces false predictions of lung immaturity.
Many laboratories have found that their procedure for determining lecithin/sphingomyelin (L/S)ratios gives an unacceptably high proportion of false predictions of fetal lung immaturity. We investigated each step in the procedure, in an attempt to improve the clinical performance of the test and to make the method more amenable to standardization between laboratories. L/S ratios were determined by the new procedure in amniotic fluid from 147 pregnancies, collected within two days of delivery of the infant. Four cases had an L/S ratio less than 2; all developed hyaline membrane disease. No other cases of hyaline membrane disease were encountered in this study. For 106 of these pregnancies, the L/S ratio was also determined by the procedure previously in use. This predicted lung immaturity for 16 infants, only four of whom developed hyaline membrane disease. All 12 cases incorrectly predicted as immature by the old procedure were correctly classified by the new procedure.


[Cost-utility of the vaccine against the Human Papiloma Virus in Peruvian women].
To estimate the cost-utility of the vaccine against the Human Papiloma Virus (HPV) in peruvian women after the application of the vaccine at 10 years of age. A cost-utility analysis was performed using the Markov´s hidden model in a hypothetical cohort of peruvian women, based on the information on epidemiological parameters, costs associated to uterine cervical cancer (UCC) and the efficacy and costs of the vaccine against the HPV. The vaccination costs were estimated from the Peruvian Ministry of Health perspective and were compared against the quality-adjusted life years (QALYs), using a discount rate of 5%. The annual cost of the vaccination was USD 16,861,490, for the Papanicoau screening it was USD 3,060,793 and the costs associated to the UCC were USD 15,580,000. The incremental cost utility ratio (ICUR) was 6,775 USD/QALY. Vaccination against HPV can be cost-utility compared to not vaccinating.


Iodine-induced goiter in penguins.
Goiter caused by excessive exposure to an iodine-containing disinfectant was an incidental finding at necropsy of captive penguins dying from renal failure, believed due to nutritional secondary hyperparathyroidism. The disease was reproduced experimentally in ducklings.


Biological monitoring of workers with past lead exposure. Biochemical findings.
In 56 subjects with lead exposure that had terminated at least 3 a previously and in a reference group of nonexposed subjects, the behavior of several biochemical indicators of dose and effect were studied. The mean values for blood lead (PbB) (1.4 +/- 0.4 mumol/l), chelatable lead (PbUEDTA) (3.4 +/- 1.5 mumol/24 h) and free erythrocyte protoporphyrin (FEP) (62 +/- 25.2 micrograms/100 ml red blood cells) were found to be significantly higher in the subjects with past lead exposure than in the referents. The cut-off levels (mean + 2 SD calculated for the reference group) of PbB, PbUEDTA and FEP were exceeded in 35.7, 67.9, and 28.6% of the exposed subjects, respectively. A normalization of lead doses and indicators of effect was reached only when the exposure had not exceeded 2 a. The time elapsed after termination of exposure did not significantly reduce the PbB level and PbUEDTA excretion, whereas these parameters correlated significantly with the length of exposure. A close correlation was found between the PbB and the PbUEDTA. Due to poor sensitivity at PbUEDTA values of less than 5.3 mumol/24 h (91% of the cases), PbB and FEP were not useful for subjects whose exposure had terminated more than 3 a earlier. In these cases, only PbUEDTA was capable of revealing elevated active lead deposits.


Refinement of breast cancer classification by molecular characterization of histological special types.
Most invasive breast cancers are classified as invasive ductal carcinoma not otherwise specified (IDC NOS), whereas about 25% are defined as histological 'special types'. These special-type breast cancers are categorized into at least 17 discrete pathological entities; however, whether these also constitute discrete molecular entities remains to be determined. Current therapy decision-making is increasingly governed by the molecular classification of breast cancer (luminal, basal-like, HER2+). The molecular classification is derived from mainly IDC NOS and it is unknown whether this classification applies to all histological subtypes. We aimed to refine the breast cancer classification systems by analysing a series of 11 histological special types [invasive lobular carcinoma (ILC), tubular, mucinous A, mucinous B, neuroendocrine, apocrine, IDC with osteoclastic giant cells, micropapillary, adenoid cystic, metaplastic, and medullary carcinoma] using immunohistochemistry and genome-wide gene expression profiling. Hierarchical clustering analysis confirmed that some histological special types constitute discrete entities, such as micropapillary carcinoma, but also revealed that others, including tubular and lobular carcinoma, are very similar at the transcriptome level. When classified by expression profiling, IDC NOS and ILC contain all molecular breast cancer types (ie luminal, basal-like, HER2+), whereas histological special-type cancers, apart from apocrine carcinoma, are homogeneous and only belong to one molecular subtype. Our analysis also revealed that some special types associated with a good prognosis, such as medullary and adenoid cystic carcinomas, display a poor prognosis basal-like transcriptome, providing strong circumstantial evidence that basal-like cancers constitute a heterogeneous group. Taken together, our results imply that the correct classification of breast cancers of special histological type will allow a more accurate prognostication of breast cancer patients and facilitate the identification of optimal therapeutic strategies.


Oral zolmitriptan is effective in the acute treatment of cluster headache.
To evaluate the efficacy and tolerability of oral zolmitriptan 5 mg and 10 mg and placebo in cluster headache. A multicenter, double-blind, randomized, three-period, crossover, outpatient study. Adult patients received placebo and zolmitriptan 5 mg and 10 mg orally for the acute treatment of episodic or chronic cluster headache. Headache intensity was rated by a five-point scale: none, mild, moderate, severe, or very severe. Patients only treated moderate to very severe headaches. The primary efficacy measure was headache response (two-point or greater reduction from baseline in the cluster headache rating scale) at 30 minutes. Secondary efficacy measures included proportion of patients with initial headache relief within 15 and 30 minutes, mild or no pain at 30 minutes, meaningful headache relief, and use of escape medication. A total of 124 patients took at least one dose of study medication, with 73% having episodic and 27% chronic cluster headache. For the primary endpoint, there was a treatment-by-cluster-headache-type interaction (p = 0.0453). Therefore, results are presented separately for chronic and episodic cluster headache. In patients with episodic cluster headache, the difference between zolmitriptan 10 mg and placebo at 30 minutes reached significance (47% versus 29%; p = 0.02). Mild or no pain at 30 minutes was reported by 60%, 57%, and 42% patients treated with zolmitriptan 10 mg, zolmitriptan 5 mg, and placebo (both p </= 0.01 versus placebo). For all other secondary endpoints, zolmitriptan 10 mg was significantly superior to placebo in episodic cluster headache patients, whereas zolmitriptan 5 mg was significantly superior to placebo for three of the four secondary endpoints. In patients with chronic cluster headache, response rates following zolmitriptan 5 mg or 10 mg were not significantly different from placebo at any endpoint. Zolmitriptan 5 mg and 10 mg were well tolerated. Oral zolmitriptan is efficacious in episodic cluster headache.


Glycosylation of recombinant rabbit immunoglobulins influences protease susceptibility as shown by comprehensive mass spectrometric glycan analysis.
Recombinant immunoglobulins (rIgGs) have become increasingly important as therapeutic agents and diagnostic tools in recent years. Genetic engineering allows the introduction of non-natural features such as the Sortase motif for site-directed labeling. In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region. However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts. Nonrecombinant Rb-IgGs have N- and O-glycans, and the presence of O-glycans close to the hinge region of the rRb-IgGs might affect the susceptibility of these antibodies to SrtA cleavage. In addition, the glycosylation pattern of rIgGs differs depending on the host cell used for expression. Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures. The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs. O-glycosylation could be mapped onto the threonine residue within the hinge region sequence XPTCPPPX, as already described previously for nonrecombinant Rb-IgGs. Substitution of this threonine allowed an almost complete Fab fragment cleavage. Therefore, we could confirm the hypothesis that the O-glycans affect the SrtA activity, probably due to steric hindrance.


The third therapeutic system: faith healing strategies in the context of a generalized AIDS epidemic.
Faith healing in sub-Saharan Africa has primarily been studied qualitatively among Pentecostal-Charismatic groups, and considered as its own phenomenon with little attention to its relationship to other modes of healing. Using data from Malawi, a religiously diverse African country with high HIV prevalence, we find that faith healing is pervasive across multiple religious traditions. For individuals, attending a faith healing congregation is associated with lower levels of generalized worry about AIDS, and this association is driven by those who switched churches before AIDS became widespread in rural areas. Use of condoms and traditional medicine are, on the other hand, positively associated with worry about AIDS. We argue that faith healing can be understood as a third therapeutic system that coexists with the well-documented biomedical and traditional systems. The success of faith healing approaches lies in their unique ability to combine individual-pragmatic and communal-ritualized aspects of healing to inform interpretations of the AIDS epidemic and its consequences.


Detailed computational analysis of a comprehensive set of group A rotavirus NSP4 proteins.
Rotavirus infection causes diarrhea to humans, animals and birds. The NSP4 protein of Group A rotavirus has been recognized as a viral enterotoxin. This single protein plays important roles in viral pathogenesis and morphogenesis. Domains involved in structure and biologic functions have been proposed mainly based on the SA11 strain, a prototype of group A rotavirus. NSP4 has been classified into different genotypes based on sequence homology. These analyses are based on representative strains selected but not comprehensive. In this paper, we collected all NSP4 sequences in the GenBank and performed a detailed computational analysis. Our analysis of 176 NSP4 proteins in Groups A, B and C rotaviruses confirms that the recently published avian NSP4 sequences belong to a new genotype (Mori Y., Borgan M.A., Ito N., Sugiyama M. and Minamoto N., Virus Res 89, 145-151, 2002), besides the four known NSP4 genotypes of Group A mammalian rotaviruses. Significant differences were discovered in the physicochemical properties between the avian and mammalian NSP4 proteins. In particular, lack of a highly probable coiled-coil region in the avian sequences implies a diversion of the NSP4 quaternary structure from the latter, although the secondary and tertiary structures may be similar. Fourteen amino acids are found absolutely conserved in the Group A NSP4 sequences, regardless of genotype. Of the conserved residues, two are glycosylation sites, one is in the middle of the transmembrane segment, seven span the VP4 binding domain, and five are clustered in the middle of the toxic peptide region, indicating the functional importance of the conservation.


Secondary data analyses of subjective outcome evaluation data based on nine databases.
The purpose of this study was to evaluate the effectiveness of the Tier 1 Program of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in Hong Kong by analyzing 1,327 school-based program reports submitted by program implementers. In each report, program implementers were invited to write down five conclusions based on an integration of the subjective outcome evaluation data collected from the program participants and program implementers. Secondary data analyses were carried out by aggregating nine databases, with 14,390 meaningful units extracted from 6,618 conclusions. Results showed that most of the conclusions were positive in nature. The findings generally showed that the workers perceived the program and program implementers to be positive, and they also pointed out that the program could promote holistic development of the program participants in societal, familial, interpersonal, and personal aspects. However, difficulties encountered during program implementation (2.15%) and recommendations for improvement were also reported (16.26%). In conjunction with the evaluation findings based on other strategies, the present study suggests that the Tier 1 Program of the Project P.A.T.H.S. is beneficial to the holistic development of the program participants.


Calcium ions modulate hormonally stimulated progesterone production in isolated ovarian cells.
Swine granulosa-luteal cells incubated in Ca2+-deficient medium (5 muM final Ca2+ concentration) for short time periods produced diminished quantities of progesterone in response to lutropin. Maximally stimulating effects of prostaglandin E2 and L-adrenaline were also impaired significantly. Diminished progesterone production could not be attributed to alterations in protein synthesis or cell viability. Under Ca2+-deprived conditions, the stimulatory actions of cholera toxin, 3-isobutyl-1-methylxanthine and 8-bromo cyclic AMP were also significantly impeded. Administration of a presumptive antagonist of transmembrane Ca2+ influx (verapamil) or of EGTA to chelate extracellular Ca2+, significantly decreased the total cellular content of Ca2+, and antagonized the actions of lutropin. Micromolar concentrations of trifluoperazine mimicked the suppressive effects of Ca2+ deprivation. Conversely, the bivalent-cation ionophore, ionophore A23187, significantly augmented the stimulation of progesterone produced by lutropin. Thus the present observations implicate Ca2+ in the modulation of hormonally stimulated progesterone production in isolated ovarian cells, and suggest that Ca2+ may influence one or more processes distal to, or independent of, cyclic AMP generation. In addition, the susceptibility of progesterone biosynthesis to inhibition by trifluoperazine suggests a possible role for calmodulin in the ovary.


A randomized, controlled trial of four ablative fractionated lasers for photoaging: a quadrant study.
Fractionated technology has revolutionized laser therapy. With the success of initial devices, several fractionated lasers have appeared on the market. Claims of superiority have made device choice difficult for physicians and patients. Twelve subjects were treated with fractionated ablative lasers (10,600-nm carbon dioxide and 2790-nm yttrium scandium gallium garnet) in this institutional review board-approved trial. Each face was divided into four quadrants, and each quadrant was randomly treated using one of four lasers. Clinical experience was used to optimize settings. Two patients submitted biopsies from each quadrant immediately after treatment. Patients and blinded investigators assessed pain during treatment and post-treatment improvement in photoaging (measured by rhytides, lentigines, texture, and pore size) using a five-point scale. All devices resulted in statistical improvement in photoaging in all patients, but no device was statistically significantly superior. No statistically significant difference was found in pain scores. All patients reported satisfaction 1 month after treatment. Three patients experienced adverse reactions. Histologically, there were no statistically significant differences between devices. Fractionated ablative lasers reliably result in improvement in photoaging. Despite marketing claims, no statistically significant differences were found in outcomes, pain during treatment, or histologic findings. Even with experienced users, significant adverse reactions are possible.


Utility of quantitative 99mTc-phytate scintigraphy to diagnose early-stage non-alcoholic steatohepatitis.
In patients with non-alcoholic fatty liver disease (NAFLD), liver biopsy remains the only reliable method to differentiate simple steatosis from non-alcoholic steatohepatitis (NASH). The objective of this study was to evaluate the efficacy of non-invasive (99m)Tc-phytate scintigraphy in the diagnosis of NASH. Thirty-seven patients with suspected NAFLD at the time of liver biopsy also underwent (99m)Tc-phytate scintigraphy. Signal intensities of regions of interest (ROI) in the liver, spleen, and heart were measured. We also examined scintigraphic features in a nutritional model of NASH in rats fed a methionine- and choline-deficient (MCD) diet. The liver/spleen uptake ratio determined by scintigraphy was significantly decreased in patients with NASH in comparison with patients with simple steatosis. The liver/spleen ratio was an independent predictor distinguishing NASH from simple steatosis. The decrease was observed for all stages of NASH, including the early stage (stages 1 and 0). In animal studies, the liver/spleen uptake ratio was significantly decreased in rats after 8 weeks of MCD dietary feeding in comparison with control diet-fed rats. The non-invasive (99m)Tc-phytate scintigraphy test is a reliable tool to differentiate NASH from simple steatosis.


Chromosomal aberrations in peripheral blood lymphocytes exposed to a mixed beam of low energy neutrons and gamma radiation.
Cells exposed to thermal neutrons are simultaneously damaged by radiations with high and low linear energy transfer (LET). A question relevant for the assessment of risk of exposure to a mixed beam is whether the biological effect of both radiation types is additive or synergistic. The aim of the present investigation was to calculate whether the high and low LET components of a thermal neutron field interact when damaging cells. Human peripheral blood lymphocytes were exposed to neutrons from the HB11 beam at the Institute for Energy and Transport, Petten, Netherlands, in a 37 °C water phantom at varying depths, where the mix of high and low LET beam components differs. Chromosomal aberrations were analysed and the relative biological effectiveness (RBE) values as well as the expected contributions of protons and photons to the aberration yield were calculated based on a dose response of aberrations in lymphocytes exposed to (60)Co gamma radiation. The RBE for 10 dicentrics per 100 cells was 3 for mixed beam and 7.2 for protons. For 20 dicentrics per 100 cells the respective values were 2.4 and 5.8. Within the limitations of the experimental setup the results indicate that for this endpoint there is no synergism between the high and low LET radiations.


The case against anergy testing as a routine adjunct to tuberculin skin testing.
Although anergy testing is commonly used to help interpret negative tuberculin skin test results, the validity of this approach has not been demonstrated. Specific issues include lack of a standardized protocol for antigen selection, number needed to reliably evaluate inability to respond, and uniform criteria for defining cutaneous reactivity, as well as regional variation in skin test reactivity. Tuberculin skin testing is used to screen for latent infection and to evaluate the need for isoniazid prophylaxis. The presence or absence of reactivity to control antigens does not affect this decision. The results of anergy testing also do not predict the risk for progression to active disease in either HIV-negative or HIV-positive patients. In HIV-negative patients with active tuberculosis, 10% to 20% have negative tuberculin test results, and 5% to 10% have a negative tuberculin result but have a positive reaction to another antigen. A negative tuberculin skin test result does not exclude either latent infection or active disease, even in the presence of a reaction to other antigens. Neither anergy testing nor tuberculin testing obviates the need for microbiologic evaluation when there is suspicion for active tuberculosis infection. Therefore, anergy testing is not useful in screening for asymptomatic tuberculous infection or for diagnosing active tuberculosis.


Immunofluorescent localization of a Ca2+-dependent neutral protease in hamster muscle.
A Ca2+-dependent neutral thiol protease is widely distributed in mammalian tissues and has been implicated in muscle protein turnover. As a first step to understanding the physiological function of this enzyme, its cellular and subcellular localization has been studied in hamster cardiac and skeletal muscle by means of indirect immunofluorescence. The results showed that the Ca2+-dependent protease is located either at the plasma membrane or in the connective tissue matrix that surrounds the muscle cels. The uniform distribution along membranes and around capillaries indicated that the protease is not confined to connective tissue cells. This evidence, together with the Ca2+-dependence of the enzyme, suggests a distribution throughout the extracellular connective tissue of the muscle. In this position, it would seem unlikely that the enzyme could participate in protein turnover within muscle cells in normal tissue.


Cervical laminoplasty developments and trends, 2003-2013: a systematic review.
Despite extensive clinical experience with laminoplasty, the efficacy of the procedure and its advantages over laminectomy remain unclear. Specific clinical elements, such as incidence or progression of kyphosis, incidence of axial neck pain, postoperative cervical range of motion, and incidence of postoperative C-5 palsies, are of concern. The authors sought to comprehensively review the laminoplasty literature over the past 10 years while focusing on these clinical elements. The authors conducted a literature search of articles in the Medline database published between 2003 and 2013, in which the terms "laminoplasty," "laminectomy," and "posterior cervical spine procedures" were used as key words. Included was every single case series in which patient outcomes after a laminoplasty procedure were reported. Excluded were studies that did not report on at least one of the above-mentioned items. A total of 103 studies, the results of which contained at least 1 of the prespecified outcome variables, were identified. These studies reported 130 patient groups comprising 8949 patients. There were 3 prospective randomized studies, 1 prospective nonrandomized alternating study, 15 prospective nonrandomized data collections, and 84 retrospective reviews. The review revealed a trend for the use of miniplates or hydroxyapatite spacers on the open side in Hirabayashi-type laminoplasty or on the open side in a Kurokawa-type laminoplasty. Japanese Orthopaedic Association (JOA) scoring was reported most commonly; in the 4949 patients for whom a JOA score was reported, there was improvement from a mean (± SD) score of 9.91 (± 1.65) to a score of 13.68 (± 1.05) after a mean follow-up of 44.18 months (± 35.1 months). The mean preoperative and postoperative C2-7 angles (available for 2470 patients) remained stable from 14.17° (± 0.19°) to 13.98° (± 0.19°) of lordosis (average follow-up 39 months). The authors found significantly decreased kyphosis when muscle/posterior element-sparing techniques were used (p = 0.02). The use of hardware in the form of hydroxyapatite spacers or miniplates did not influence the progression of deformity (p = 0.889). An overall mean (calculated from 2390 patients) of 47.3% loss of range of motion was reported. For the studies that used a visual analog scale score (totaling 986 patients), the mean (cohort size-adjusted) postoperative pain level at a mean follow-up of 29 months was 2.78. For the studies that used percentages of patients who complained of postoperative axial neck pain (totaling 1249 patients), the mean patient number-adjusted percentage was 30% at a mean follow-up of 51 months. The authors found that 16% of the studies that were published in the last 10 years reported a C-5 palsy rate of more than 10% (534 patients), 41% of the studies reported a rate of 5%-10% (n = 1006), 23% of the studies reported a rate of 1%-5% (n = 857), and 12.5% reported a rate of 0% (n = 168). Laminoplasty remains a valid option for decompression of the spinal cord. An understanding of the importance of the muscle-ligament complex, plus the introduction of hardware, has led to progress in this type of surgery. Reporting of outcome metrics remains variable, which makes comparisons among the techniques difficult.


Comparative interactomics provides evidence for functional specialization of the nuclear pore complex.
The core architecture of the eukaryotic cell was established well over one billion years ago, and is largely retained in all extant lineages. However, eukaryotic cells also possess lineage-specific features, frequently keyed to specific functional requirements. One quintessential core eukaryotic structure is the nuclear pore complex (NPC), responsible for regulating exchange of macromolecules between the nucleus and cytoplasm as well as acting as a nuclear organizational hub. NPC architecture has been best documented in one eukaryotic supergroup, the Opisthokonts (e.g. Saccharomyces cerevisiae and Homo sapiens), which although compositionally similar, have significant variations in certain NPC subcomplex structures. The variation of NPC structure across other taxa in the eukaryotic kingdom however, remains poorly understood. We explored trypanosomes, highly divergent organisms, and mapped and assigned their NPC proteins to specific substructures to reveal their NPC architecture. We showed that the NPC central structural scaffold is conserved, likely across all eukaryotes, but more peripheral elements can exhibit very significant lineage-specific losses, duplications or other alterations in their components. Amazingly, trypanosomes lack the major components of the mRNA export platform that are asymmetrically localized within yeast and vertebrate NPCs. Concomitant with this, the trypanosome NPC is ALMOST completely symmetric with the nuclear basket being the only major source of asymmetry. We suggest these features point toward a stepwise evolution of the NPC in which a coating scaffold first stabilized the pore after which selective gating emerged and expanded, leading to the addition of peripheral remodeling machineries on the nucleoplasmic and cytoplasmic sides of the pore.


Relationships Between Adipose Mitochondrial Function, Serum Adiponectin, and Insulin Resistance in Persons With HIV After 96 Weeks of Antiretroviral Therapy.
Some antiretroviral therapy (ART) and HIV itself confer metabolic risk, perhaps through altered mitochondrial function and adipokines. In AIDS Clinical Trials Group study A5224s, adipose mitochondrial DNA (mtDNA) levels decreased on ART, and electron transport chain complex I (CI) and complex IV (CIV) activity decreased. Another study found decreased serum adiponectin on ART with mtDNA mutation m.10398A>G. We hypothesized that decreased adipose tissue mitochondrial function would be associated with lower adiponectin and insulin sensitivity on ART, and m.10398G would influence these changes. Retrospective analysis of an ART-naive substudy population from A5224s. Analyses included adipose mtDNA levels, CI and CIV activity by immunoassay, visceral adipose tissue by computed tomography, and fasting serum glucose at week 0 and week 96 of ART. Fasting insulin and adiponectin were measured from cryopreserved serum using multiplex bead array. Homeostasis model assessment-2 (HOMA2)-IR and HOMA2-%B estimated insulin resistance and β-cell function, respectively. The m.10398A>G mtDNA variant was available from existing genetic data. Thirty-seven participants had adipose biopsies at week 0 and week 96. Percent decreases in CIV activity and adiponectin were correlated (Spearman rho 0.41; P = 0.01); this association persisted after controlling for age, sex, body mass index, or visceral adipose tissue in single-covariate regression. HOMA2-IR correlated with decreased CIV (-0.44; P = 0.01) and CI (-0.34; P = 0.05) activity. Among 12 non-Hispanic white persons, m.10398G was associated with decreased adiponectin (P = 0.04). Decreased adipose mitochondrial activity correlated with changes in adiponectin and glucose homeostasis on ART. Previous findings that a mtDNA mutation modulates adiponectin levels in persons with HIV were replicated.


Phospholipid transfer protein (PLTP) deficiency reduces brain vitamin E content and increases anxiety in mice.
Vitamin E supplementation constitutes a promising strategy in the prevention of neurodegenerative diseases. Here, we show that a phospholipid transfer protein (PLTP) is widely expressed in the brain where it appears to function as a transfer factor for alpha-tocopherol, the main isomer of vitamin E. PLTP deficiency results in significant depletion of brain alpha-tocopherol in both homozygous (-30.1%, P<0.0002) and heterozygous (-18.0%, P<0.05) PLTP knocked-out mice. Alpha-tocopherol depletion in PLTP-deficient homozygotes is associated with the elevation of lipofuscin (+25% and +450% increases in cortex and substantia nigra, respectively), cholesterol oxides (+54.5%, P<0.05), and cellular peroxides (+32.3%, P<0.01) in the brain. Complete PLTP deficiency in homozygotes is accompanied by increased anxiety as shown by fewer entries (8.3% vs. 44.4% in controls, P<0.01) and less time spent (1.7% vs. 41.3% in controls, P<0.05) in the open arms of an elevated plus-maze, in the absence of locomotor deterioration. Thus, the vitamin E transfer activity of PLTP appears to be a key process in preventing oxidative damage in the brain, and PLTP-deficient mice could be a new model of the contribution of oxidative brain injury in the etiology of neurodegenerative diseases.


Phosphatidylinositol 3-kinase coordinately activates the MEK/ERK and AKT/NFkappaB pathways to maintain osteoclast survival.
We have examined highly purified osteoclasts that were generated in vitro from murine co-culture of marrow precursors with stromal support cells and have found evidence of activation of the MEK/ERK and AKT/NFkappaB survival pathways. Many mature marrow-derived osteoclasts survived for at least 48 h in culture whether or not they are maintained with stromal cells. Moreover, supplementing purified osteoclasts with RANKL and/or M-CSF had no impact on their survival pattern. In addition, spleen-derived osteoclasts generated with RANKL and M-CSF treatment exhibited a similar survival pattern. Blocking MEK, AKT, or NFkappaB activity resulted in apoptosis of many, but not all, of the osteoclasts in purified marrow-derived osteoclasts, marrow-derived osteoclasts co-cultured with stromal cells, and spleen-derived osteoclasts maintained with RANKL and M-CSF. These data support that both the MEK/ERK and AKT/NFkappaB pathways contribute to osteoclast survival. Since PI3K has been shown to activate either of these pathways, we have examined its role in osteoclast survival. PI3K inhibition caused apoptosis of nearly all osteoclasts in purified and co-cultured marrow-derived osteoclasts and spleen-derived osteoclasts maintained with RANKL and M-CSF. Interestingly, in marrow-derived co-cultures, the apoptotic response was restricted to osteoclasts as there was no evidence of stromal support cell apoptosis. PI3K inhibition also blocked MEK1/2, ERK1/2, and AKT phosphorylation and NFkappaB activation in purified osteoclasts. Simultaneous blockage of both AKT and MEK1/2 caused rapid apoptosis of nearly all osteoclasts, mimicking the response to PI3K inhibition. These data reveal that PI3K coordinately activates two distinct survival pathways that are both important in osteoclast survival.


Rapid Neuronal Ultrastructure Disruption and Recovery during Spreading Depolarization-Induced Cytotoxic Edema.
Two major pathogenic events that cause acute brain damage during neurologic emergencies of stroke, head trauma, and cardiac arrest are spreading depolarizing waves and the associated brain edema that course across the cortex injuring brain cells. Virtually nothing is known about how spreading depolarization (SD)-induced cytotoxic edema evolves at the ultrastructural level immediately after insult and during recovery. In vivo 2-photon imaging followed by quantitative serial section electron microscopy was used to assess synaptic circuit integrity in the neocortex of urethane-anesthetized male and female mice during and after SD evoked by transient bilateral common carotid artery occlusion. SD triggered a rapid fragmentation of dendritic mitochondria. A large increase in the density of synapses on swollen dendritic shafts implies that some dendritic spines were overwhelmed by swelling or merely retracted. The overall synaptic density was unchanged. The postsynaptic dendritic membranes remained attached to axonal boutons, providing a structural basis for the recovery of synaptic circuits. Upon immediate reperfusion, cytotoxic edema mainly subsides as affirmed by a recovery of dendritic ultrastructure. Dendritic recuperation from swelling and reversibility of mitochondrial fragmentation suggests that neurointensive care to improve tissue perfusion should be paralleled by treatments targeting mitochondrial recovery and minimizing the occurrence of SDs.


Exposure to the riot control agent CS and potential health effects: a systematic review of the evidence.
o-Chlorobenzylidene malononitrile (CS) is one of the most extensively used riot control agents. Our aim was to conduct a systematic review of the potential health effects related to CS exposure. We searched for papers in English between 1991 and 2014. Thirty five (35) studies (25 case reports, seven descriptive studies and three analytical studies) were included in the review. In the twenty five case reports/series 90 cases of exposure to CS and their clinical effects are presented. Their mean age was 25.7 years and 62.0% were males. In addition, 61% of the cases described dermal, 40% respiratory, 57% ocular clinical effects. Life threatening situations as well as long-term health effects were found and were related with exposure to confined/enclosed space. Descriptive and analytical studies have shown attack rates ranging from 12% to 40%. Subjects who were sprayed by the police more often needed special treatment and reported adverse health effects. Apart from transient clinical effects, CS could have lasting and serious effects on human health. Better surveillance of the subjects exposed to CS and completion of cohort studies among exposed populations will illuminate the spectrum of the health effects of exposure to CS.


Mid-IR multiwavelength difference frequency generation based on fiber lasers.
A mid-IR multiwavelength difference frequency generation (DFG) laser source with fiber laser fundamental lights is demonstrated by using the dispersion property of PPLN to broaden the quasi-phase-matching (QPM) acceptance bandwidth (BW). Our results show that the QPM BW for the pump YDFL is much larger than that for the signal EDFL. Using a multiwavelength YDFL and a single-wavelength EDFL as the pump and the signal lights, the DFG laser source can simultaneously emit 14 mid-IR wavelengths with the spacing of 14 nm at a fixed PPLN temperature. Moreover, mid-IR multiwavelength lasing lines can be synchronously tuned between 3.28 and 3.47 microm.


Effects of Chronic Consumption of Sugar-Enriched Diets on Brain Metabolism and Insulin Sensitivity in Adult Yucatan Minipigs.
Excessive sugar intake might increase the risk to develop eating disorders via an altered reward circuitry, but it remains unknown whether different sugar sources induce different neural effects and whether these effects are dependent from body weight. Therefore, we compared the effects of three high-fat and isocaloric diets varying only in their carbohydrate sources on brain activity of reward-related regions, and assessed whether brain activity is dependent on insulin sensitivity. Twenty-four minipigs underwent 18FDG PET brain imaging following 7-month intake of high-fat diets of which 20% in dry matter weight (36.3% of metabolisable energy) was provided by starch, glucose or fructose (n = 8 per diet). Animals were then subjected to a euglycemic hyperinsulinemic clamp to determine peripheral insulin sensitivity. After a 7-month diet treatment, all groups had substantial increases in body weight (from 36.02±0.85 to 63.33±0.81 kg; P<0.0001), regardless of the diet. All groups presented similar insulin sensitivity index (ISI = 1.39±0.10 mL·min-1·μUI·kg). Compared to starch, chronic exposure to fructose and glucose induced bilateral brain activations, i.e. increased basal cerebral glucose metabolism, in several reward-related brain regions including the anterior and dorsolateral prefrontal cortex, the orbitofrontal cortex, the anterior cingulate cortex, the caudate and putamen. The lack of differences in insulin sensitivity index and body weight suggests that the observed differences in basal brain glucose metabolism are not related to differences in peripheral insulin sensitivity and weight gain. The differences in basal brain metabolism in reward-related brain areas suggest the onset of cerebral functional alterations induced by chronic consumption of dietary sugars. Further studies should explore the underlying mechanisms, such as the availability of intestinal and brain sugar transporter, or the appearance of addictive-like behavioral correlates of these brain functional characteristics.


Focus on Functional Delayed Central Sleep Apnea Following Cervical Laminectomy. An Example of Respiratory Dysfunction in Restorative Neurosurgical Procedures.
In sleep-related breathing disorders, sleep apnea is a clinical symptom that can be categorized as obstructive sleep apnea (OSA) or mixed apnea by analysis using polysomnography. The occurrence of delayed central sleep apnea (CSA) is an extremely rare complication of cervical laminectomy for spondylotic myelopathy. So far only three studies concerning such an event have been reported in the literature. Naim-ur-Rahman, in 1994, reported a case of postoperative CSA following C3-C6 laminectomy, and Visocchi and colleagues, in 2014, in two studies, stressed the lack of association with any other neurological sign of spinal cord damage. No definitive mechanism has been recognized so far for delayed CSA after cervical laminectomy. A transient dysfunction of the reticulo-spinal fibers directed to the nucleus of the phrenic nerve can be speculated, although neither emi-diaphragm paralysis, nor any prominent nocturnal sleep-related disorders are associated with this delayed CSA.


Cryptic diversity hides host and habitat specialization in a gorgonian-algal symbiosis.
Shallow water anthozoans, the major builders of modern coral reefs, enhance their metabolic and calcification rates with algal symbionts. Controversy exists over whether these anthozoan-algae associations are flexible over the lifetimes of individual hosts, promoting acclimative plasticity, or are closely linked, such that hosts and symbionts co-evolve across generations. Given the diversity of algal symbionts and the morphological plasticity of many host species, cryptic variation within either partner could potentially confound studies of anthozoan-algal associations. Here, we used ribosomal, organelle and nuclear sequences, along with microsatellite variation, to study the relationship between lineages of a common Caribbean gorgonian and its algal symbionts. The gorgonian Eunicea flexuosa is a broadcast spawner, composed of two recently diverged, genetically distinct lineages largely segregated by depth. We sampled colonies of the two lineages across depth gradients at three Caribbean locations. We find that each host lineage is associated with a unique Symbiodinium B1/184 phylotype. This relationship between host and symbiont is maintained when host colonies are reciprocally transplanted, although cases of within phylotype switching were also observed. Even when the phylotypes of both partners are present at intermediate depths, the specificity between host and symbiont lineages remained absolute. Unrecognized cryptic diversity may mask host-symbiont specificity and change the inference of evolutionary processes in mutualistic associations. Symbiotic specificity thus likely contributes to the ecological divergence of the two partners, generating species diversity within coral reefs.


Ia antigens and Fc receptors of mouse peritoneal macrophages as determinants of susceptibility to lactic dehydrogenase virus.
The relationship between susceptibility of mouse peritoneal macrophages to lactic dehydrogenase-elevating virus (LDV) infection and expression of I region-coded antigens (Ia) on these cells was investigated. The proportion of Ia-positive cells in resident peritoneal macrophages from adult and suckling mice were 4 to 10% and 50 to 70% respectively. Approximately the same percentage of the cells were susceptible to LDV, as detected by fluorescent antibody staining. In adult mice, double-labelling experiments showed that most of the Ia-positive cells were LDV-infected. When the cells were cultured for more than 24 h in vitro, Ia-positive cells rapidly disappeared and the culture became resistant to LDV. Removal of Ia-positive cells by treatment with anti-Ia plus complement or enrichment using an anti-Ia-coated Petri dish simultaneously removed or enriched for LDV-susceptible cells. Treatment of cells with trypsin (1 mg/ml) removed their I-A and I-E antigens and simultaneously abolished susceptibility for LDV. When LDV was preincubated with subneutralizing amounts of antibody, infectivity for macrophages was enhanced and the proportion of LDV-infected cells was higher than that of Ia-positive cells. This suggests that Fc receptors on macrophages can act as receptors for LDV coated with antiviral IgG.


Misuse and abuse of pregabalin and gabapentin: cause for concern?
Gabapentinoids (e.g. pregabalin and gabapentin) are widely used in neurology, psychiatry and primary healthcare but are increasingly being reported as possessing a potential for misuse. In fact, increasing levels of both prescriptions and related fatalities, together with an anecdotally growing black market, have been reported from a range of countries. This article reviews the current evidence base of this potential, in an attempt to answer the question of whether there is cause for concern about these drugs. Potent binding of pregabalin/gabapentin at the calcium channel results in a reduction in the release of excitatory molecules. Furthermore, gabapentinoids are thought to possess GABA-mimetic properties whilst possibly presenting with direct/indirect effects on the dopaminergic 'reward' system. Overall, pregabalin is characterized by higher potency, quicker absorption rates and greater bioavailability levels than gabapentin. Although at therapeutic dosages gabapentinoids may present with low addictive liability levels, misusers' perceptions for these molecules to constitute a valid substitute for most common illicit drugs may be a reason of concern. Gabapentinoid experimenters are profiled here as individuals with a history of recreational polydrug misuse, who self-administer with dosages clearly in excess (e.g. up to 3-20 times) of those that are clinically advisable. Physicians considering prescribing gabapentinoids for neurological/psychiatric disorders should carefully evaluate a possible previous history of drug abuse, whilst being able to promptly identify signs of pregabalin/gabapentin misuse and provide possible assistance in tapering off the medication.


PBMC transcriptomic responses to primary and secondary vaccination differ due to divergent lean growth and antibody titers in a pig model.
The genetic relationship between immune responsiveness and performance is not well understood, but a major topic of the evolution of resource allocation and of relevance in human medicine and livestock breeding, for instance. This study aims to show differences of transcript abundance changes during the time intervals before and after two tetanus toxoid (TT) vaccinations in domestic pigs differing in lean growth (LG) and anti-TT-antibody titers (AB) parameters of performance and immunocompetence. During response to the first vaccination all animals had a general decrease in transcript abundances related to various functional pathways as measured by comparative Affymetrix microarray hybridization and Ingenuity Pathway analyses. Low-AB phenotypes had predominantly decreased immune response transcripts. Combined phenotypes high-AB/high-LG had decreased transcripts related to growth factor signaling pathways. However, during the interval after the booster vaccination, high-LG and high-AB animals responded exclusively with increased immune transcripts, such as B-cell receptor signaling and cellular immune response pathways. In addition, high-LG and low-AB animals had predominantly increased transcripts of several cellular immune response pathways. Conversely, low-LG and high-AB animals had few elevated immune transcripts and decreased transcripts related to only two nonimmune-specific pathways. In response to booster vaccination high-LG phenotypes revealed enriched transcripts related to several different immune response pathways, regardless of AB phenotype. Different from the expected impact of AB titers, divergent AB phenotypes did not reflect considerable differences between immune transcripts. However, highly significant differences observed among divergent LG phenotypes suggest the compatibility of high performance and high vaccine responses.


Effect of Oxytocin on Hunger Discrimination.
Centrally and peripherally administered oxytocin (OT) decreases food intake and activation of the endogenous OT systems, which is associated with termination of feeding. Evidence gathered thus far points to OT as a facilitator of early satiation, a peptide that reduces the need for a meal that has already begun. It is not known, however, whether OT can diminish a feeling of hunger, thereby decreasing a perceived need to seek calories. Therefore, in the current project, we first confirmed that intraperitoneal (i.p.) OT at 0.3-1 mg/kg reduces food intake in deprived and non-deprived rats. We then used those OT doses in a unique hunger discrimination protocol. First, rats were trained to discriminate between 22- and 2-h food deprivation (hungry vs. sated state) in a two-lever operant procedure. After rats acquired the discrimination, they were food-restricted for 22 h and given i.p. OT before a generalization test session. OT did not decrease 22-h deprivation-appropriate responding to match that following 2-h food deprivation, thus, it did not reduce the perceived level of hunger. In order to better understand the mechanisms behind this ineffectiveness of OT, we used c-Fos immunohistochemistry to determine whether i.p. OT activates a different subset of feeding-related brain sites under 22- vs. 2-h deprivation. We found that in sated animals, OT induces c-Fos changes in a broader network of hypothalamic and brain stem sites compared to those affected in the hungry state. Finally, by employing qPCR analysis, we asked whether food deprivation vs. sated state have an impact on OT receptor expression in the brain stem, a CNS "entry" region for peripheral OT. Fasted animals had significantly lower OT receptor mRNA levels than their ad libitum-fed counterparts. We conclude that OT does not diminish a feeling of hunger before a start of a meal. Instead OT's anorexigenic properties are manifested once consumption has already begun which is-at least to some extent-driven by changes in brain responsiveness to OT treatment in the hungry vs. fed state. OT should be viewed as a mediator of early satiation rather than as a molecule that diminishes perceived hunger.


Positron emission tomography of murine liver metastases and the effects of treatment by combretastatin A-4.
There are major potential advantages in non-invasive measurement of preclinical tumour biology and therapeutic response in clinically relevant, internal body sites, notably the ability to follow outcome in individual animals rather than averaging results from groups. We have exploited positron emission tomography (PET) to determine the feasibility of detecting liver metastases in B6D2F1 mice using fluorine-18 fluorodeoxyglucose ([18F]FDG) both before and after treatment by the novel cytotoxic agent, combretastatin A-4. The normal distribution of [18F]FDG in the absence of disease was characterised, with the clear delineation of the brain, the heart and the urinary bladder in all studies. In untreated mice with liver metastases, a strong correlation (r2 = 0.98) was found between the quantitative estimates of [18F]FDG uptake obtained by analysis of PET images, and those obtained from ex vivo assay of liver plus metastases excised immediately after imaging. In this first series, the effective limit of resolution was in livers containing a number of small metastases (range 8-14) with a single volume equivalent of approximately 200 mm3. PET image analysis was concordant with histological measurements in showing that single intraperitoneal doses of combretastatin A-4 resulted in an average 30% volume destruction of metastatic mass by 24 h following administration.


Cigarette smoking saturates brain alpha 4 beta 2 nicotinic acetylcholine receptors.
2-[18F]fluoro-3-(2(S)-azetidinylmethoxy) pyridine (2-F-A-85380, abbreviated as 2-FA) is a recently developed radioligand that allows for visualization of brain alpha 4 beta 2* nicotinic acetylcholine receptors (nAChRs) with positron emission tomography (PET) scanning in humans. To determine the effect of cigarette smoking on alpha 4 beta 2* nAChR occupancy in tobacco-dependent smokers. Fourteen 2-FA PET scanning sessions were performed. During the PET scanning sessions, subjects smoked 1 of 5 amounts (none, 1 puff, 3 puffs, 1 full cigarette, or to satiety [2(1/2) to 3 cigarettes]). Academic brain imaging center. Eleven tobacco-dependent smokers (paid volunteers). Main Outcome Measure Dose-dependent effect of smoking on occupancy of alpha 4 beta 2* nAChRs, as measured with 2-FA and PET in nAChR-rich brain regions. Smoking 0.13 (1 to 2 puffs) of a cigarette resulted in 50% occupancy of alpha 4 beta 2* nAChRs for 3.1 hours after smoking. Smoking a full cigarette (or more) resulted in more than 88% receptor occupancy and was accompanied by a reduction in cigarette craving. A venous plasma nicotine concentration of 0.87 ng/mL (roughly 1/25th of the level achieved in typical daily smokers) was associated with 50% occupancy of alpha 4 beta 2* nAChRs. Cigarette smoking in amounts used by typical daily smokers leads to nearly complete occupancy of alpha 4 beta 2* nAChRs, indicating that tobacco-dependent smokers maintain alpha 4 beta 2* nAChR saturation throughout the day. Because prolonged binding of nicotine to alpha 4 beta 2* nAChRs is associated with desensitization of these receptors, the extent of receptor occupancy found herein suggests that smoking may lead to withdrawal alleviation by maintaining nAChRs in the desensitized state.


Impaired vasodilator responses in obstructive sleep apnea are improved with continuous positive airway pressure therapy.
Obstructive sleep apnea causes cardiovascular morbidity and premature death. Potential links between sleep apnea and cardiovascular complications are chronically elevated activity of the sympathetic nervous system and abnormal vascular function. To explore vascular function, we determined the reactive hyperemic blood flow (RHBF) responses to 10 minutes of forearm arterial occlusion (plethysmography), blood pressure, and muscle sympathetic nerve activity (MSNA, microneurography) in eight patients with sleep apnea and in nine nonapneic control subjects. Peak RHBF and vascular conductance were markedly attenuated in sleep apnea compared with control subjects (p < 0.05). Seven sleep apnea patients were retested after at least two weeks of continuous positive airway pressure (CPAP) therapy. MSNA decreased after CPAP therapy (p < 0.05, n = 6), whereas blood pressure did not change. After CPAP therapy, peak RHBF and vascular conductance were increased compared with before treatment (p < 0.05; n = 7). Thus, vascular function is abnormal in sleep apnea and is improved by CPAP therapy. Furthermore, effective CPAP therapy decreases sympathetic activity in sleep apnea. Thus, sympathoexcitation and abnormal vascular function in patients with sleep apnea appear to be linked to the repetitive nocturnal apneic events.


Projecting global fertilizer consumption under shared socioeconomic pathway (SSP) scenarios using an approach of ensemble machine learning.
Comprehensively predicting global fertilizer consumption is essential for providing critical datasets in related fields such as earth system simulation, the fertilizer industry, and agricultural sciences. However, since previous studies have not fully considered the socioeconomic factors affecting fertilizer consumption, huge uncertainties may remain in fertilizer consumption projections. Here, an approach ensembled six machine learning algorithms was proposed in this study to predict global fertilizer consumption from 2020 to 2100 by considering the impact of socioeconomic factors under shared socioeconomic pathway (SSP) scenarios. It indicates that the proposed approach provides a rational and reliable framework for fertilizer consumption prediction that stably outperforms the single algorithms with relatively high accuracy (Nash-Sutcliffe efficiency of 0.93, Kling-Gupta efficiency of 0.89, and mean absolute percentage error of 10.97 %). We found that global N and P fertilizer consumption may decrease from 2020 to 2100, while K fertilizer may buck the trend. N fertilizer consumption showed a declining trend of -1 %, -17.13 %, and - 3.43 % under the SSP1, SSP2, and SSP3 scenarios in 2100, respectively. For P fertilizer, those were - 0.68 %, -9.68 %, and - 2.03 %. In contrast, global K fertilizer consumption may increase by 18.03 %, 9.18 %, and 6.74 %, respectively. On average, N, P, and K fertilizer consumption is highest in China, and the lowest is in Kazakhstan. However, the hotspots of N fertilizer consumption may shift from China to Latin America and the Caribbean. This study highlighted the EML approach could potentially be a robust method for predicting future fertilizer consumption. Our prediction product will not only contribute to a better understanding of global fertilizer consumption trends and dynamics but also provide flexible and accurate key data/parameters for related research. The Projected Global Fertilizers Consumption Datasets are available at doi:https://doi.org/10.5281/zenodo.8195593 (Gao et al., 2023).


Identity and collective action via computer-mediated communication: A review and agenda for future research.
Since the start of large-scale waves of mobilisation in 2011, the importance of identity in the study of collective action via computer-mediated communication (CMC) has been a source of contention. Hence, our research sets out to systematically review and synthesise empirical findings on identity and collective action via CMC from 2012 to 2016. We found that the literature on the topic is broad and diverse, with contributions from multiple disciplines and theoretical and methodological approaches. Based on our findings, we provide directions for future research and propose the adoption of an integrative approach that combines the study of identity and networks to advance our understanding of collective action via CMC. This review contributes to the crossroad of social movement, collective action, communication and media studies. Our results also have practical implications for the organisation of collective action in a society characterised by the pervasive influence of CMC.


Strategies of blood collection in Cote d'Ivoire: impact of mobile collection methods on the production of the National Blood Transfusion Service, 2014-2016.
Blood product suppliers have two options for blood collection: at fixed sites and mobile collection sites. Those preferring voluntary, unpaid donations must move ever closer to the population by organizing mobile collection. The objective of this study was to analyze the impact of mobile collection in the production of the Côte d'Ivoire's CNTS. Our results, based on data from the CNTS from 2014 through 2016 and interviews with 22 managers of blood transfusion centers, confirm the increasing preponderance of this approach. Thus, our results raise the problem of blood safety in a context where the prevalence of transfusion-transmissible infections is higher in mobile collections, where most donors are giving blood for the first time.


Comparison of serological methods (ELISA, DAT and IFA) for diagnosis of visceral leishmaniasis utilizing an endemic strain.
The causative agent of visceral leishmaniasis (VL) in Iran is Leishmania infantum (L. infantum) (Mediterranean type) and its major reservoir host is the dog. To compare the serological methods including direct agglutination test (DAT), indirect immunofluorescent-antibody test (IFA) and enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of endemic strain of L. infantum. 61 blood samples from VL patients referred to Shiraz hospitals and 49 blood samples from control group were collected. Native strain of the parasite isolated from a VL patient from the region was cultured and characterized. Antigens from this L. infantum parasite were used in ELISA and IFA system. Anti-Leishmania antibody was detected in 43 (70.5%), 49 (80.3%) and 51(83.6%) cases using DAT, IFA and ELISA, respectively. Based on these results, sensitivity and specificity of DAT was found to be 70.5% and 100%, respectively. Sensitivities of IFA and ELISA in diagnosis of VL were 80.3% and 83.6% and their specificity was 90.5%. Results of this study showed that DAT and ELISA have the highest specificity and sensitivity in diagnosis of VL. DAT is a simple, cost-effective and field applicable test. Thus, it can be recommended for early and accurate diagnosis of VL, especially in regions where malaria, brucellosis and tuberculosis are prevalent.


In vivo characterization of myocardial infarction using fluorescence and diffuse reflectance spectroscopy.
We explore the feasibility of using combined fluorescence and diffuse reflectance spectroscopy to characterize a myocardial infarct at different developing stages. An animal study is conducted using rats with surgically induced myocaridal infarction (MI). In vivo fluorescence spectra at 337-nm excitation and diffuse reflectance between 400 and 900 nm are measured from the heart. Spectral acquisition is performed: 1. for normal heart tissue; 2. for the area immediately surrounding the infarct; and 3. for the infarcted tissue itself, one, two, three, and four weeks into MI development. Histological and statistical analyses are used to identify unique pathohistological features and spectral alterations associated with the investigated regions. The main alterations (p<0.05) in diffuse reflectance spectra are identified primarily between 450 and 600 nm. The dominant fluorescence alterations are increases in peak fluorescence intensity at 400 and 460 nm. The extent of these spectral alterations is related to the duration of the infarction. The findings of this study support the concept that optical spectroscopy could be useful as a tool to noninvasively determine the in vivo pathophysiological features of a myocardial infarct and its surrounding tissue, thereby providing real-time feedback to surgeons during various surgical interventions for MI.


Mechanisms of protein import into mitochondria.
Apart from a handful of proteins encoded by the mitochondrial genome, most proteins residing in this organelle are nuclear-encoded and synthesised in the cytosol. Thus, delivery of proteins to their final destination depends on a network of specialised import components that form at least four main translocation complexes. The import machinery ensures that proteins earmarked for the mitochondrion are recognised and delivered to the organelle, transported across membranes, sorted to the correct compartment and assisted in overcoming energetic barriers.


Defining futile life-prolonging treatments through Neo-Socratic Dialogue.
In Japan, people are negative towards life-prolonging treatments. Laws that regulate withholding or discontinuing life-prolonging treatments and advance directives do not exist. Physicians, however, view discontinuing life-prolonging treatments negatively due to fears of police investigations. Although ministerial guidelines were announced regarding the decision process for end-of-life care in 2007, a consensus could not be reached on the definition of end-of-life and conditions for withholding treatment. We established a forum for extended discussions and consensus building on this topic. We used the Neo-Socratic Dialogue (NSD) method which promotes philosophical discussion based on a case-study to address a question and formulate a consensus and answer in a group. The question chosen for the dialogue was: "What is a life-prolonging treatment?" A series of dialogues took place over a period of one and a half days. It was carried out by three groups in 2010 and 2011. Seven participants with diverse backgrounds were recruited per group. We analyzed the content of the discussion. Based on three case studies concerning different opinions about treatment options for an older dementia patient, a patient demanding chemotherapy, and a severely ill neonate, conditions for futile life-prolonging treatment were elucidated through NSD. Such treatments are those carried out for the sole purpose of prolonging life and are detrimental to the patient, and should be decided based foremost on the patient's lack of desire for treatment, the consensus of those involved, and through social acceptance. These arguments are essentially consistent with ones on medical futility in the United States. By expressing the objective of healthcare and the requirement of social acceptance, participants were also able to elucidate issues related to the awareness of those involved and the medical environment. Compared to the end-of-life guidelines in Japan, the objective of treatment, its effects, and benefits were more specifically discussed with the patient's intentions as the foremost consideration, rather than being limited to the terminal stage. This small study contributed to elucidating the conditions and current problems of futile life-prolonging treatment through NSD. They would suggest more substantial guidelines and improvements on the administration of the treatment.


Biomimetic Urban and Architectural Design: Illustrating and Leveraging Relationships between Ecosystem Services.
Redesigning and retrofitting cities so they become complex systems that create ecological and cultural-societal health through the provision of ecosystem services is of critical importance. Although a handful of methodologies and frameworks for considering how to design urban environments so that they provide ecosystem services have been proposed, their use is not widespread. A key barrier to their development has been identified as a lack of ecological knowledge about relationships between ecosystem services, which is then translated into the field of spatial design. In response, this paper examines recently published data concerning synergetic and conflicting relationships between ecosystem services from the field of ecology and then synthesises, translates, and illustrates this information for an architectural and urban design context. The intention of the diagrams created in this research is to enable designers and policy makers to make better decisions about how to effectively increase the provision of various ecosystem services in urban areas without causing unanticipated degradation in others. The results indicate that although targets of ecosystem services can be both spatially and metrically quantifiable while working across different scales, their effectiveness can be increased if relationships between them are considered during design phases of project development.


K18-hACE2 Mice for Studies of COVID-19 Treatments and Pathogenesis Including Anosmia.
The ongoing COVID-19 pandemic is associated with substantial morbidity and mortality. While much has been learned in the first months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation and many patients with this finding show no or only minor respiratory signs. Studies in animals experimentally infected with SARS-CoV-2, the cause of COVID-19, provide opportunities to study aspects of the disease not easily investigated in human patients. COVID-19 severity ranges from asymptomatic to lethal. Most experimental infections provide insights into mild disease. Here, using K18-hACE2 mice that we originally developed for SARS studies, we show that infection with SARS-CoV-2 causes severe disease in the lung, and in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Further, we show that infusion of convalescent plasma (CP) from a recovered COVID-19 patient provided protection against lethal disease. Mice developed anosmia at early times after infection. Notably, while treatment with CP prevented significant clinical disease, it did not prevent anosmia. Thus K18-hACE2 mice provide a useful model for studying the pathological underpinnings of both mild and lethal COVID-19 and for assessing therapeutic interventions.


Dissonance in Music Impairs Spatial Gait Parameters in Patients with Parkinson's Disease.
It is known that music influences gait parameters in Parkinson's disease (PD). However, it remains unclear whether this effect is merely due to temporal aspects of music (rhythm and tempo) or other musical parameters. To examine the influence of pleasant and unpleasant music on spatiotemporal gait parameters in PD, while controlling for rhythmic aspects of the musical signal. We measured spatiotemporal gait parameters of 18 patients suffering from mild PD (50%men, mean±SD age of 64±6 years; mean disease duration of 6±5 years; mean Unified PD Rating scale [UPDRS] motor score of 15±7) who listened to eight different pieces of music. Music pieces varied in harmonic consonance/dissonance to create the experience of pleasant/unpleasant feelings. To measure gait parameters, we used an established analysis of spatiotemporal gait, which consists of a walkway containing pressure-receptive sensors (GAITRite®). Repeated measures analyses of variance were used to evaluate effects of auditory stimuli. In addition, linear regression was used to evaluate effects of valence on gait. Sensory dissonance modulated spatiotemporal and spatial gait parameters, namely velocity and stride length, while temporal gait parameters (cadence, swing duration) were not affected. In contrast, valence in music as perceived by patients was not associated with gait parameters. Motor and musical abilities did not relevantly influence the modulation of gait by auditory stimuli. Our observations suggest that dissonant music negatively affects particularly spatial gait parameters in PD by yet unknown mechanisms, but putatively through increased cognitive interference reducing attention in auditory cueing.


Trajectory of systolic blood pressure in a low-income, racial-ethnic minority cohort with diabetes and baseline uncontrolled hypertension.
In two primary care clinics in Texas serving low-income patients, systolic blood pressure (SBP) trajectory was examined during 2 years in patients with diabetes mellitus (mean SBP ≥140 mm Hg: 152 mm Hg±11.2 in the baseline year). Among 860 eligible patients, 62.0% were women, 78.8% were Hispanic, and 41.2% were uninsured. Overall, SBP dropped 0.56 mm Hg per month or 13.4 mm Hg by 24 months. For patients with mean glycated hemoglobin ≥9% in year 1, SBP declined 4.8 mm Hg less by 24 months vs those with glycated hemoglobin <7% (P=.03). Compared with white women, SPB declined 7.2 mm Hg less by 24 months in Hispanic women (P=.03) and 9.6 mm Hg less by 24 months in black men (P=.04). SBP also declined 9.1 mm Hg less by 24 months for patients taking four or more blood pressure drug classes at baseline vs one drug class. In this low-income cohort, clinically complex patients and racial-ethnic minorities had clinically significantly smaller declines in SBP.


Are risk factors for patellofemoral and tibiofemoral knee osteoarthritis different?
To determine whether patellofemoral (PF), tibiofemoral (TF), and combined patterns of knee osteoarthritis (OA) differ in their strengths of associations with any of the known risk factors for knee OA, and especially to evaluate whether body mass index (BMI) correlates with all 3 patterns, or only with tibiofemoral disease, as previously suggested. We obtained anteroposterior and lateral knee radiographs on 608 participants at the 22nd biennial examination of the Framingham cohort study (1992-3). The presence or absence of OA in the TF and PF compartments of each knee was scored, and subjects were classified on the basis of the pattern of compartmental involvement in their 2 knees. The strength of association of age, sex, BMI, chondrocalcinosis, and knee injury was computed for PF, TF, and combined pattern of knee OA using multiple logistic regression. The mean age and BMI of the sample were 80.7 yrs (SD 5.0) and 25.4.kg-2 (SD 3.7), respectively. PF, TF, and combined patterns of knee OA were present in 5.3, 23.0 and 19.7%, respectively. Elevated BMI was a risk factor for all 3 patterns of disease (adjusted OR for highest vs lowest tertile of BMI 3.7, 1.9, and 7.0 for PF, TF, and combined pattern, respectively). Risk factor profiles were broadly similar for TF and PF OA, with the possible exception of knee injury in men (adjusted OR = 2.0 for PF, 3.7 for TF OA). Risk factors were generally more strongly associated with the combined pattern of OA. Obesity is an important risk factor for PF, TF, and combined patterns of knee OA. The relationships of these patterns with the risk factors investigated here appear similar and are strongest for the combined pattern.


Readiness of Health Centers and Primary Hospitals for the Implementation of Proposed Health Insurance Schemes in Southwest Ethiopia.
In response to the 2005 World Health Assembly, many low income countries developed different healthcare financing mechanisms with risk pooling stategy to ensure universal coverage of health services. Accordingly, service availability and readiness of the health system to bear the responsibility of providing service have critical importance. The objective of this study was to assess service availability and readiness of health centers and primary hospitals to bear the responsibility of providing service for the members of health insurance schemes. A facility based cross sectional study design with quantitative data collection methods was employed. Of the total 18 districts in Jimma Zone, 6(33.3%) districts were selected randomly. In the selected districts, there were 21 functional public health facilities (health centers and primary hospitals) which were included in the study. Data were collected by interviewer administered questionnaire. Descriptive statistics were calculated by using SPSS version 20.0. Prior to data collection, ethical clearance was obtained. Among the total 21 public health facilities surveyed, only 38.1% had all the categories of health professionals as compared to the national standards. The majority, 85.2%, of the facilities fulfilled the criteria for basic equipment, but 47.7% of the facilities did not fulfill the criteria for infection prevention supplies. Moreover, only two facilities fulfilled the criteria for laboratory services, and 95.2% of the facilities had no units/departmenst to coordinate the health insurance schemes. More than nine out of ten facilities did not fulfill the criteria for providing healthcare services for insurance beneficiaries and are not ready to provide general services according to the standard. Hence, policy makers and implementers should devise strategies to fill the identified gaps for successful and sustainable implementation of the proposed insurance scheme.


Temporomandibular Joint Dislocation in a Patient with Keratoconus Under General Anesthesia: A Case Report.
Keratoconus is a common disease in which the central or paracentral cornea undergoes progressive thinning, resulting in a cone-shaped cornea. It has been associated with many systemic disorders such as Down syndrome, osteogenesis imperfecta, and joint hypermobility. Herein, temporomandibular joint dislocation under general anesthesia during supraglottic airway device placement before deep anterior lamellar keratoplasty procedure in a keratoconus patient is reported.


Assessment of digenean parasitism in Nassarius reticulatus (L.) along the Portuguese coast: evaluation of possible impacts on reproduction and imposex expression.
A survey was performed between June and September 2006 along the Portuguese coast to assess the prevalence of digenean parasitism in the netted whelk Nassarius reticulatus, a bioindicator of tributyltin (TBT) pollution. It was also intended to evaluate the effect of parasites on the reproduction of this gastropod species and their interference on the development of imposex (the superimposition of male characters onto prosobranch females) and male penis, based on field data. Five digenean species (Lepocreadium album, Gynaecotyla longiintestinata, Himasthla quissetensis, Diphtherostomum brusinae, and Cardiocephalus longicollis), plus 1 unidentified species, were found to infect N. reticulatus. Parasitism was spread along the Portuguese coast, but the higher values of prevalence were found in sheltered inshore areas where up to 67.4% of the animals were affected per sampling station. Parasitism has a castrating impact on the whelks and a reducing effect on male penis size, which causes serious disorders in the reproduction of N. reticulatus and may have an important impact in its population dynamics. However, no relationship between imposex severity and parasite infestation was found.


Mutations in the phosphoglucose isomerase gene can lead to marked alterations in cellular ATP levels in cultured fibroblasts exposed to simple nutrient shifts.
The generation of ATP in a hamster fibroblast mutant devoid of the enzyme phosphoglucose isomerase (PGI) has been studied and compared with that in the parental line, which is PGI+. Both cell lines could be maintained for 24 hr in hexose media devoid of L-glutamine. Under these conditions in mannose medium, both the parental line and the PGI mutant maintained high intracellular ATP levels. With glucose under the same conditions, the parental line was able to keep the ATP level high. In contrast, the mutant line lost most of its ATP pool after incubation with glucose; the ATP/ADP ratio fell about 80% after incubation in glucose medium. Addition of pyruvate, with or without glucose, preserved the ATP pool at high levels even in the mutant, as did the presence of L-glutamine. When the PGI mutant was maintained for 3-4 days in growth medium, containing 4 mM L-glutamine and 10% dialyzed calf serum, in which glucose was replaced by mannose, the UDP-glucose pool dwindled and mediated control of the hexose uptake system did not ensue, in contrast to results of the same exposure to glucose-containing medium.


Tight junction proteins in the canine epidermis: a pilot study on their distribution in normal and in high IgE-producing canines.
Epidermal tight junctions (TJ) have been well-described in human medicine and are involved in many skin diseases such as atopic dermatitis (AD). In dogs, there are no data regarding the implication of TJ in skin diseases including canine AD. The aim of this study was to compare the expression and the distribution of ZO-1, occludin and claudin-1 in the epidermis of healthy and atopic dogs. Skin biopsies from 6 high IgE-producing beagles sensitized to house dust mite (atopic group) were used. Skin specimens from nine healthy dogs without skin issues were sampled (healthy group). Immunoperoxydase staining was used to study the staining pattern of zonula occludens-1 (ZO-1), occludin and claudin-1 in the epidermis of healthy and atopic dogs. Positive controls were healthy human skin samples. Labeling patterns were assessed by 2 examiners blinded to the identities of the specimens. Comparisons between groups were performed using an exact Wilcoxon-Mann-Whitney test. The mean total expression score of claudin-1 was lower in atopic dogs as compared to healthy subjects. Occludin and ZO-1 expression remained unchanged within each group. These results suggest a defect in claudin-1 expression in the nonlesional epidermis of atopic dogs.


The g protein-coupled receptor agtrl1b regulates early development of myocardial progenitors.
While many factors that modulate the morphogenesis and patterning of the embryonic heart have been identified, relatively little is known about the molecular events that regulate the differentiation of progenitor cells fated to form the myocardium. Here, we show that zebrafish grinch (grn) mutants form a reduced number of myocardial progenitor cells, which results in a profound deficit in cardiomyocyte numbers in the most severe cases. We show that grn encodes the G protein-coupled receptor (GPCR) Agtrl1b, a known regulator of adult cardiovascular physiology. Ectopic expression of Apelin, an Agtrl1b ligand, results in the complete absence of cardiomyocytes. Data from transplantation and transgenic approaches indicate that Agtrl1 signaling plays a cell-autonomous role in myocardial specification, with activity being required coincident with the onset of gastrulation movements. These results support a model in which agtrl1b regulates the migration of cells fated to form myocardial progenitors.