[Hemocytes of the blowfly Calliphora vicina and their dynamics during larval development and metamorphosis].
On the basis of in vitro observation of live cells and examination of stained slides of larval and prepupal Calliphora vicina hemolymph, seven types of hemocytes have been detected: prohemocytes, stable and unstable hyaline cells, thrombocytoids, spindle cells, larval plasmatocytes, and plasmatocytes I-IV, a. The last representing sequential stages of one cell line differentiation. Prohemocytes are basic cells, from which other forms of hemocytes derive outside the hemopoietic tissue, i.e. in free hemolymph. At the last larval instar, three waves of hemopoiesis occur. Either wave tends to increase the general number of cells and to change the quality of hemocyte population. The first wave occurs at the close of larva feeding and is accompanied by increase in the number of hyaline hemocytes, thrombocytoids and larval plasmatocytes. The second wave of hemopoiesis occurs after the larva's crop emptying. In this period the main increase of hemocyte population occurs at the expense of prohemocytes and plasmatocytes I. The most significant (five-fold) explosion of the population of free hemocytes takes place at the onset of pupariation and correlates with the rise of ecdysone titer. At the first stage of this peak, the amount of plasmatocytes I sharply increases. Further on these are rapidly differentiated into plasmatocytes II and III. After the puparium formation, hemocytes are reduced in number. Plasmatocytes III phagocytose fragments of destroyed larval tissues, pass to the stage of plasmatocytes IV (macrophages), and partially settle on tissues.


Low expression of Kv7/M channels facilitates intrinsic and network bursting in the developing rat hippocampus.
Early in development, network activity in the hippocampus is characterized by recurrent synchronous bursts, whose cellular correlates are giant depolarizing potentials (GDPs). The propensity for generating GDPs is attributed to GABAergic synaptic transmission being depolarizing and excitatory in neonatal neurons. However, developmental regulation of intrinsic conductances may also influence GDPs generation. A likely candidate is the non-inactivating, low-threshold, muscarinic-sensitive K(+) current (M current; I(m)), which down-regulates intrinsic bursting activity in adult hippocampal pyramidal neurons. Western blot analysis of homogenates of the CA3 hippocampal region showed that expression of the Kv7.2 subunit, one of the constituents of neuronal M channels, is weak in neonatal neurons, and markedly increases after the first postnatal week. Likewise, the density of I(m) was very low in neonatal CA3 pyramidal cells and increased later on. Spontaneously occurring intrinsic bursts in neonatal neurons were longer and more robust, and recurred more regularly, than in juvenile neurons. The I(m) blocker linopirdine only mildly affected intrinsic bursting in neonatal neurons, but strongly facilitated and regularized it in juvenile neurons. We conclude that the low expression of Kv7/M channels and the depolarizing action of GABA early after birth enhance intrinsic bursting and neuronal synchronization leading to generation of GDPs within the hippocampal network.


A heuristic risk assessment technique for birdstrike management at airports.
Collisions between birds and aircraft (birdstrikes) have caused the loss of at least 88 aircraft and 243 lives in world civil aviation. Conservative estimates suggest that more routine damage and delays following birdstrikes cost the industry and its insurers US$1.2-1.5 billion per year. The majority of strikes happen close to airports and most countries have regulations that require airport managers to control the birdstrike risk on their property. Birdstrike prevention has, however, lagged behind other aspects of flight safety in the development and implementation of risk assessment protocols, possibly because of the inherent difficulty in quantifying the variability in the populations and behavior of the various bird species involved. This article presents a technique that uses both national and airport-specific data to evaluate risk by creating a simple probability-times-severity matrix. It uses the frequency of strikes reported for different bird species at a given airport over the preceding five years as a measure of strike probability, and the proportion of strikes with each species that result in damage to aircraft, in the national birdstrike database, as a measure of likely severity. Action thresholds for risk levels for particular bird species are then defined, above which the airport should take action to reduce the risk further. The assessment is designed for airports where the reporting and collation of birdstrike events is reasonably consistent over time and where a bird hazard management program of some sort is already in place. This risk assessment is designed to measure risk to the airport as a business rather than risk to the traveling passenger individually. It therefore takes no account of aircraft movement rate in the calculations and is aimed at minimizing the number of damaging incidents rather than concentrating on catastrophic events. Once set up at an airport, the technique is simple to implement for nonexperts, and it allows managers to focus bird control resources on the species causing the greatest risk, hence maximizing the return on investment. This protocol is now being successfully used at major airports in the United Kingdom and elsewhere in the world.


Joint trajectories of cognition and gait speed in Mexican American and European American older adults: The San Antonio longitudinal study of aging.
Cognitive decline and gait speed slowing are independent predictors of disability and mortality. While both factors increase in prevalence with advancing age, little is known about their combined patterns of change. The study goal was to identify joint trajectories of cognition and gait speed within an aging bi-ethnic cohort of Mexican Americans and European Americans. Participants included 182 Mexican Americans and 188 European Americans, ages 65 to 74, who were followed over a mean of 9.5 years. Cognition was assessed with the mini-mental state examination and gait speed was examined with a timed 10-ft walk. Joint trajectory classes of cognition and gait speed were identified with latent growth mixture modeling. Odd-ratios assessed predictors for trajectory classes. Three latent trajectory classes were identified: (a) relatively stable cognition and gait (termed stable cognition and gait class, 65.4%); (b) deteriorating cognition and gait (termed cognitive and physical vulnerability class, 22.2%); (c) stable cognition and deteriorating gait (termed physical vulnerability class, 12.4%). The odds of classification in the cognitive and physical vulnerability class vs stable cognition and gait class was associated with Mexican American ethnicity (OR = 3.771, P = .016), age (OR = 1.186, P = .017), income (OR = 0.828, P = .029), education (OR = 0.703, P < .001), and diabetes (OR = 4.547, P = .010). The odds of classification in the physical vulnerability class was associated with female sex (OR = 6.481, P = .004) and body mass index (OR = 1.118, P = .025). The trajectories of cognition and gait speed were generally parallel, suggesting the two domains may act synergistically to shape important health outcomes. Socioeconomic disparities and Mexican American ethnicity independently conferred risk for accelerated decline.


Entomological assessment of the transmission following recrudescence of onchocerciasis in the Comoé Valley, Burkina Faso.
Onchocerciasis, or river blindness, is a dermal filariasis caused by infection with the nematode parasite Onchocerca volvulus, transmitted to humans through the bites of blackflies of the genus Simulium. Despite the decade-long West African Regional Programme for the Elimination of Onchocerciasis, involving the mass administration of ivermectin to populations in endemic areas, recrudescence has occurred. An example is in the Cascades Region of south-west Burkina Faso where the resumption of transmission had resulted in infection prevalences of up to 70% in some villages. In 2011, a strategy for community-directed distribution of ivermectin (CDTI) was set up to respond to this worrying re-emergence. Here, we report on a study of Onchocerca spp. transmission in the affected area carried out from January to December 2012. Every month, host-seeking adult females of the S. damnosum complex were collected at sites on the River Comoé near the four villages (Bodadiougou, Bolibana, Badara Karaboro and Badara Dogossè) that had recorded the highest prevalences in 2010. Collected blackflies were dissected and infective larvae were identified using the O-150 PCR method. A total of 9114 S. damnosum (s.l.) adult females were collected, of which 5142 were parous (56.4%) and 78 (1.51%) were infective carrying a total of 137 infective larvae. The annual transmission potential (ATP) was calculated as 0, 30, 255 and 771 infective larvae/man/year in Badara Dogossè, Bolibana, Badara Karaboro and Bodadiougou, respectively. Transmission levels in the latter two are of particular concern as they were higher than 100 infective larvae/person/year, the designated minimum threshold required for elimination of severe pathology, including damage to vision. These results confirm that recrudescence of onchocerciasis has occurred, and that transmission of O. volvulus was active at sites on the Comoé River in the Cascades region in 2012. In accordance with WHO recommendations, CDTI should be continued and the situation in the Cascades region should be closely monitored if further spread of this outbreak is to be avoided.


Vaccina treatment in some hospital infections.
Phenol-treated vaccine was prepared from the usual hospital strains and patients with colorectal cancer were immunized intramuscularly 7-10 days prior to the operation. The efficiency of the vaccine treatment was judged by the incidence of wound infections. The best results were obtained in patients whose previously estimated immunoreactivity was strong or normal. Immunospecificity could not be detected in the above treatment. The frequent and inappropriate use of antibiotics in hospitals increases the number of resistant hospital bacterial strains. Apart from Staphylococci and Streptococci, different Gram-negatives--such as Klebsiella, Serratia, Pseudomonas, Proteus and E. coli strains--have been found in the hospitals and in the patients. Due to the resistance, it is difficult to find antibiotics against them. This fact puts forward the possibility of immunization especially by vaccination.


Exploration of the illness uncertainty concept in acute and chronic pain patients vs community patients.
Illness uncertainty (IU) theory proposes that patients with chronic illness may have difficulty adjusting to the illness if there is significant diagnostic or prognostic uncertainty. Two dimensions of IU theory are "lack of information about diagnoses or severity of the illness" (LIDSI) and "complexity regarding the health care system" (CRHCS). The primary objective of this study was then to compare the prevalence of IU in community nonpatients, community patients, and rehabilitation patients without pain/chronic pain patients (CPPs)/acute pain patients (APPs) as represented by two items with possible face validity for LIDSI ("doctors puzzled by my problems,""doctors missed something important") and three items with possible CRHCS face validity ("doctors don't believe me,""I need to prove my problem is real,""doctors think my problems are in my head"). The secondary objectives were to determine if the LIDSI items are associated with the CRHCS items and to develop predictor models for the LIDSI items in APPs and CPPs. The Battery for Health Improvement Research (BHI-R) version was administered to a healthy (pain-free) community sample (N = 1,478), community patient sample (N = 158), rehabilitation patients without pain (N = 110), rehabilitation APPs (N = 326), and rehabilitation CPPs (N = 341). The IU LIDSI and CRHCS items were contained within the BHI-R. These five patient groups were compared for the risk of endorsement of these items. Correlations were developed between the LIDSI and CRHCS items in APPs and CPPs. APPs and CPPs that affirmed IU items were compared with those not affirming the item on a wide range of demographic variables and Behavior Health Inventory (BHI 2) scales. Significant variables (P < or = 0.01) were then utilized as independent variables in predictor models for the LIDSI items. Community patients and nonpatients, patients from physical therapy/work hardening/chronic pain/vocational rehabilitation programs, and physicians' offices. Affirmation for the LIDSI items ranged from 5.04% (community healthy) to 24.9% (CPPs) and for the CRHCS items, from 3.16% (community healthy) to 29.6% (CPPs). CPPs were significantly more likely than community patients to endorse one of the LIDSI items (doctors puzzled by my problem) plus all the CRHCS items. APPs, however, were no more likely than community patients to endorse any LIDSI IU items and two out of the three CRHCS items. LIDSI items were significantly correlated with the CRHCS items in both APPs and CPPs. The following items entered the final logistic regression models for LIDSI in APPs and CPPs: CRHCS items (APPs); items from the Doctor Dissatisfaction scale of the BHI 2 and the scale itself (APPs and CPPS); items related to faulty patient memory (APPs and CPPs); and various other items such as "hard muscles," etc. The models classified 87% (puzzling medical problem) and 91% (doctors missed something) of the APPs correctly. For CPPs, the models classified 79% (puzzling medical problem) and 88% (doctors missed something) of the patients correctly. None of these classifications, however, were better than the base rate. LIDSI and CRHCS IU is not unusual in nonpatient and patient groups. However, rehabilitation CPPs are at significantly greater risk than community patients for LIDSI and CRHCS IU. LIDSI IU is associated with CRHCS IU, and LIDSI IU is predicted by a large number of items, the most notable of these being perception of not being believed and dissatisfaction with the physician.


Iterative range estimation in a sloping-bottom shallow-water waveguide using the generalized array invariant.
The array invariant theory was generalized by incorporating the waveguide invariant β, referred to as the generalized array invariant. In this paper, the generalized array invariant is extended to mildly range-dependent environments with a sloping bottom where the waveguide invariant is variable in range. Assuming knowledge of the bottom slope, the array invariant can be applied iteratively to estimate the source range starting with β = 1 (i.e., range-independent), which converges toward the correct source range by updating β at the previously estimated range. The iterative array invariant approach is demonstrated using a short-aperture vertical array (2.8-m) in a sloping-bottom shallow-water waveguide from the Random Array of Drifting Acoustic Receivers 2007 experiment, where a high-frequency source (2-3.5 kHz) close to the surface (6-m) was towed between 0.5 and 5 km in range with the water depth varying from 80 to 50 m.


Small steps towards the potential of 'preventive' treatment of early phosphate loading in chronic kidney disease patients.
Few clinical studies have investigated the value of phosphate (P)-lowering therapies in early chronic kidney disease (CKD) patients in whom hyperphosphataemia has not yet clearly developed and they report conflicting and even unexpected results. In this issue of Clinical Kidney Journal, de Krijger et al. found that sevelamer carbonate (4.8 g/day for 8 weeks) did not induce a significant reduction of pulse wave velocity (PWV) and that fibroblast growth factor 23 (FGF23) did not decrease despite a decline in 24-h urine P excretion. To some extent these findings challenge the concept that 'preventive' P binder therapy to lower FGF23 is a useful approach, at least over this short period of time. Interestingly, in a subgroup of patients with absent or limited abdominal vascular calcification, treatment did result in a statistically significant reduction in adjusted PWV, suggesting that PWV is amenable to improvement in this subset. Interpretation of the scarce and heterogeneous observations described in early CKD remains difficult and causality and/or the possibility of 'preventive' treatment may not yet be completely disregarded. Moreover, de Krijger et al. contribute to the identification of new sources of bias and methodological issues that may lead to more personalized treatments, always bearing in mind that not all patients and not all P binders are equal.


Lipopolysaccharide activates microglia via neuraminidase 1 desialylation of Toll-like Receptor 4.
Most cell surface receptors are sialylated, i.e. have sialic acid as the terminal residue of their sugar chains, but can be desialylated by sialidases, such as neuraminidase 1 (Neu1). Desialylation by Neu1 can activate immune cells, such as neutrophils, macrophages and monocytes. We investigated the role of Neu1 in activation of microglia using BV-2 cells (a murine microglial cell line) by cytokine ELISAs, enzyme activity assays, antibody/lectin binding and proximity labelling. We found that lipopolysaccharide (LPS) activation caused an increase in Neu1 protein on the cell surface, and an increase in surface sialidase activity that was prevented by Neu1 knockdown. Moreover, LPS induced interleukin 6 (IL-6) and MCP-1 release, which was reduced by Neu1 knockdown and increased by Neu1 over-expression. Neu1 knockdown also prevented the maintenance of IL-6 release by microglia after LPS was removed. Sialidase treatment of the cells was sufficient to induce IL-6 release, prevented by inhibiting toll-like receptor 4 (TLR4). Neu1 was found in close proximity to TLR4 on the surface of cells, and LPS induced desialylation of TLR4 on the cell surface, prevented by Neu1 knockdown. Sialic acid-binding immunoglobulin-like lectin E was found to bind to TLR4 via sialic acid residues and inhibit IL-6 release by BV-2 cells. We conclude that LPS causes Neu1 to translocate to the cell surface, where it desialylates TLR4, releasing inhibitory sialic acid-binding immunoglobulin-like lectin E, enhancing and maintaining inflammatory activation of the microglia. Thus, sialylation is a potent regulator of microglial activation, and Neu1 may be a target to reduce activation of microglia.


Germline stem cell division and egg chamber development in transplanted Drosophila germaria.
Germline and somatic stem cells reside within the anterior region (or "germarium") of each ovariole in the Drosophila ovary. When individual germaria were dissected free of developing eggs and sheath tissue and transplanted into the abdominal cavity of a host fly, they regenerated ovariole-like structures and continuously supported the entire process of oogenesis, indicating that the stem cells remained functional. This system allowed us to measure the duration of several stages in oogenesis and to analyze the role of specific germarial cells in providing stem cell function. Laser ablation of presumptive germline stem cells near the apical tip prior to transplantation blocked the production of new germline cysts, but allowed previously initiated cysts to complete development. This confirmed the location of germline stem cells and showed that subsequent development of preexisting cysts did not require continued cyst production. Ablation of a distinct group of somatic cells lying close to the germline stem cells ("the terminal filament") increased the rate of oogenesis by approximately 40%, suggesting that the terminal filament may negatively regulate stem cell division.


Mathematical modeling of light-mediated HPA axis activity and downstream implications on the entrainment of peripheral clock genes.
In this work we propose a semimechanistic model that describes the photic signal transduction to the hypothalamic-pituitary-adrenal (HPA) axis that ultimately regulates the synchronization of peripheral clock genes (PCGs). Our HPA axis model predicts that photic stimulation induces a type-1 phase response curve to cortisol's profile with increased cortisol sensitivity to light exposure in its rising phase, as well as the shortening of cortisol's period as constant light increases (Aschoff's first rule). Furthermore, our model provides insight into cortisol's phase and amplitude dependence on photoperiods and reveals that cortisol maintains highest amplitude variability when it is entrained by a balanced schedule of light and dark periods. Importantly, by incorporating the links between HPA axis and PCGs we were able to investigate how cortisol secretion impacts the entrainment of a population of peripheral cells and show that disrupted light schedules, leading to blunted cortisol secretion, fail to synchronize a population of PCGs which further signifies the loss of circadian rhythmicity in the periphery of the body.


[Effect of 7,12-dimethylbenz(alpha)anthracene metabolites on its capacity to induce skin tumors in mice].
Induction of skin tumors by 7,12-dimethylbenz(a)anthracene (DMBA) in the presence of its metabolites-7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHM-12-MBA) and 7,12-dihydroxymethylbenz(a)anthracene (7,12-diOHMBA) has been studied in mice. The skin of mice was treated repeatedly with benzene or acetone solutions of DMBA (22 mug in two droplets) or with the same amount of DMBA solution together with one of the above mentioned metabolites (the molecular ratio 1 : 1 or 1 : 0.5). Neither of the metabolites affected the carcinogenic activity of DMBA under the given conditions. 7,8-benzoflavone, an inhibitior of the DMBA metabolism, strongly suppressed DMBA tumorigenesis under the same experimental conditions. Whereas the effect of benz(a)-anthracene, an inducer of aryl hydrocarbon hydroxylase activity, was less pronounced.


Competition: an antidote to the high price of prescription drugs.
Patent protection and factors unique to prescription drugs weaken the forces keeping prices near costs for other products. A growing public consensus that affordable drugs should be available to all is likely to increase the upward pressure on prices. To restore competition to all parts of the pharmaceutical industry, we propose a new institute at the National Institutes of Health that would compete with the private sector for pharmaceutical intellectual property by establishing competition for research and development contracts open to public and private institutions; retain the resulting patents; and grant cost-free, nonexclusive licenses to all qualified producers.


A phase II trial of gefitinib monotherapy in chemotherapy-naïve patients of 75 years or older with advanced non-small cell lung cancer.
Gefitinib has shown modest activity in patients with recurrent non-small cell lung cancer (NSCLC) after platinum-based chemotherapy. However, the activity of gefitinib as first-line chemotherapy remains unclear, especially unknown in elderly patients. A multicenter phase II trial was conducted to evaluate the efficacy and tolerability of gefitinib for elderly patients with chemotherapy-naïve NSCLC. Elderly chemotherapy-naïve patients with advanced NSCLC, ECOG PS of 0-2, and adequate organ functions received 250 mg/day of gefitinib. The primary objective of this study was to determine the objective response rate (RR). Secondary endpoints were tolerability, disease-related symptom using lung cancer subscale (LCS) in FACT-L, progression free survival (PFS) and overall survival (OS). We investigated mutation status of the epidermal growth factor receptor (EGFR) gene in cases with available tumor samples. Fifty patients were enrolled, of whom 49 were eligible. Median age (range) was 80 (75-90) years. Thirty-two patients were female (65%) and 40 patients had adenocarcinoma (82%). The objective RR was 25% (CI 95%, 13-39). Median survival time was 10 months (CI 95%, 7-20) and 1-year survival rate was 50%. The most frequent adverse events were skin disorders (76%). Fifteen patients (30%) experienced toxicities >/=grade 3. There were four patients with possible interstitial lung disease including two treatment-related deaths. Symptom improvement rate using LCS was 49% at 4 weeks of gefitinib therapy. Tumor samples from 17 patients were analyzed for EGFR mutation status. EGFR mutations were detected in tumor tissues from 7 patients, of which 5 had partial responses (71%). Gefitinib monotherapy is effective and relatively well tolerated in chemotherapy-naïve elderly patients with advanced NSCLC. Gefitinib has potential as a first-line therapeutic option in elderly patients with advanced NSCLC.


Artificial neural network retrained to detect myocardial ischemia using a Japanese multicenter database.
An artificial neural network (ANN) has been applied to detect myocardial perfusion defects and ischemia. The present study compares the diagnostic accuracy of a more recent ANN version (1.1) with the initial version 1.0. We examined 106 patients (age, 77 ± 10 years) with coronary angiographic findings, comprising multi-vessel disease (≥ 50% stenosis) (52%) or old myocardial infarction (27%), or who had undergone coronary revascularization (30%). The ANN versions 1.0 and 1.1 were trained in Sweden (n = 1051) and Japan (n = 1001), respectively, using 99mTc-methoxyisobutylisonitrile myocardial perfusion images. The ANN probabilities (from 0.0 to 1.0) of stress defects and ischemia were calculated in candidate regions of abnormalities. The diagnostic accuracy was compared using receiver-operating characteristics (ROC) analysis and the calculated area under the ROC curve (AUC) using expert interpretation as the gold standard. Although the AUC for stress defects was 0.95 and 0.93 (p = 0.27) for versions 1.1 and 1.0, respectively, that for detecting ischemia was significantly improved in version 1.1 (p = 0.0055): AUC 0.96 for version 1.1 (sensitivity 87%, specificity 96%) vs. 0.89 for version 1.0 (sensitivity 78%, specificity 97%). The improvement in the AUC shown by version 1.1 was also significant for patients with neither coronary revascularization nor old myocardial infarction (p = 0.0093): AUC = 0.98 for version 1.1 (sensitivity 88%, specificity 100%) and 0.88 for version 1.0 (sensitivity 76%, specificity 100%). Intermediate ANN probability between 0.1 and 0.7 was more often calculated by version 1.1 compared with version 1.0, which contributed to the improved diagnostic accuracy. The diagnostic accuracy of the new version was also improved in patients with either single-vessel disease or no stenosis (n = 47; AUC, 0.81 vs. 0.66 vs. p = 0.0060) when coronary stenosis was used as a gold standard. The diagnostic ability of the ANN version 1.1 was improved by retraining using the Japanese database, particularly for identifying ischemia.


Social-spatial network structures among young urban and suburban persons who inject drugs in a large metropolitan area.
Recent studies underscore the significance of adopting a syndemics approach to study opioid misuse, overdose, hepatitis C (HCV) and HIV infections, within the broader context of social and environmental contexts in already marginalized communities. Social interactions and spatial contexts are crucial structural factors that remain relatively underexplored. This study examines the intersections of social interactions and spatial contexts around injection drug use. More specifically, we investigate the experiences of different residential groups among young (aged 18-30) people who inject drugs (PWID) regarding their social interactions, travel behaviors, and locations connected to their risk behaviors. By doing so, we aim to achieve a more comprehensive understanding of the multidimensional risk environment, thereby facilitating the development of informed policies. We collected and examined data regarding young PWID's egocentric injection network and geographic activity spaces (i.e., where they reside, inject drugs, purchase drugs, and meet sex partners). Participants were stratified based on the location of all place(s) of residence in the past year i.e., urban, suburban, and transient (both urban and suburban) to i) elucidate geospatial concentration of risk activities within multidimensional risk environments based on kernel density estimates; and ii) examine spatialized social networks for each residential group. Participants were mostly non-Hispanic white (59%); 42% were urban residents, 28% suburban, and 30% transient. We identified a spatial area with concentrated risky activities for each residential group on the West side of Chicago in Illinois where a large outdoor drug market area is located. The urban group (80%) reported a smaller concentrated area (14 census tracts) compared to the transient (93%) and suburban (91%) with 30 and 51 tracts, respectively. Compared to other areas in Chicago, the identified area had significantly higher neighborhood disadvantages. Significant differences were observed in social network structures and travel behaviors: suburban participants had the most homogenous network in terms of age and residence, transient participants had the largest network (degree) and more non-redundant connections, while the urban group had the shortest travel distance for all types of risk activities. Distinct residential groups exhibit varying patterns of network interaction, travel behaviors, and geographical contexts related to their risk behaviors. Nonetheless, these groups share common concentrated risk activity spaces in a large outdoor urban drug market area, underscoring the significance of accounting for risk spaces and social networks in addressing syndemics within PWID populations.


Role of foetal echocardiography in predicting perinatal outcome.
To establish foetal cardiovascular parameters as predictors of perinatal outcome in pregnancy, M-Mode, 2-D echocardiography and pulse Doppler study was performed at 24-32 weeks of gestation in 65 pregnancies. These pregnancies were followed up for perinatal outcome. The studied population included 24 normal pregnancies, 21 pregnant women with heart disease (14 rheumatic and 7 congenital heart disease) and 20 high risk pregnancies (bad obstetric history in 7, suspected intrauterine growth retardation in 4, hypertensive disease of pregnancy in 6 and diabetes mellitus in 3). There was no perinatal mortality. Two foetuses were born with complete heart block and one with a small ventricular septal defect; 6 neonates had intrauterine growth retardation and two of these had neonatal asphyxia with APGAR score less than 6 at one minute. Anatomically normal heart was correctly diagnosed in all 64 foetuses and ventricular septal defect was detected antenatally in one. Antenatal diagnosis of complete heart block was correctly made in two foetuses. One new born with complete heart block required a permanent pacemaker, which was implanted. The ratio of peak velocity across mitral valve during atrial systole (A) to peak velocity during early diastolic ventricular filling (E) was chosen to correlate with perinatal outcome. The ratio was less than 1.0 in 6 foetuses, all of whom were subsequently confirmed to have intrauterine growth retardation. In normal pregnancies A/E ratio was more than 1.0. We conclude that foetal echocardiography is a useful tool for predicting perinatal outcome and may be helpful in screening patients who require specific perinatal management.


clbP Gene, a Potential New Member of the β-Lactamase Family.
The colibactin island (pks) of Escherichia coli formed by 19 genes (55-Kb), encodes non-ribosomal peptide (NRP) and polyketide (PK) synthases, which allow the synthesis of colibactin, a suspected hybrid PK-NRP compound that causes damage to DNA in eukaryotic cells. The clbP, an unusual essential gene, is found in the operon structure with the clbS gene in the pks-encoded machinery. Interestingly, the clbP gene has been annotated as a β-lactamase but no previous study has reported its β-lactamase characteristics. In this study, we (i) investigated the β-lactamase properties of the clbP gene in silico by analysing its phylogenetic relationship with bacterial β-lactamase and peptidase enzymes, (ii) compared its three-dimensional (3D) protein structure with those of bacterial β-lactamase proteins using the Phyr2 database and PyMOL software, and (iii) evaluated in vitro its putative enzymatic activities, including β-lactamase, nuclease, and ribonuclease using protein expression and purification from an E. coli BL21 strain. In this study, we reveal a structural configuration of toxin/antitoxin systems in this island. Thus, similar to the toxin/antitoxin systems, the role of the clbP gene within the pks-island gene group appears as an antitoxin, insofar as it is responsible for the activation of the toxin, which is colibactin. In silico, our analyses revealed that ClbP belonged to the superfamily of β-lactamase, class C. Furthermore, in vitro we were unable to demonstrate its β-lactamase activity, likely due to the fact that the clbP gene requires co-expression with other genes, such as the genes present in the pks-island (19 genes). More research is needed to better understand its actions, particularly with regards to antibiotics, and to discover whether it has any additional functions due to the importance of this gene and its toxicity.


Accentuating patient values in shared decision-making: A mixed methods development of an online value clarification tool and communication training in the context of early phase clinical cancer trials.
In the shared decision-making (SDM) process for potential early phase clinical cancer trial participation, value clarification is highly recommended. However, exploration and discussion of patient values between patients and oncologists remains limited. This study aims to develop an SDM-supportive intervention, consisting of a preparatory online value clarification tool (OnVaCT) and a communication training. The OnVaCT intervention was developed and pilot-tested by combining theoretical notions on value clarification, with interview studies with patients and oncologists, focus groups with patient representatives and oncologists, and think aloud sessions with patients, following the Medical Research Council (MRC) framework for complex interventions. These human-centered methodologies enabled a user-centered approach at every step of the development process of the intervention. This study shows relevant patient values and oncologists' perspectives on value exploration and discussion in daily practice. This has been combined with theoretical considerations into the creation of characters based on real-life experiences of patients in the OnVaCT, and how the tool is combined with a communication training for oncologists to improve SDM.


Revised Hammersmith Scale for spinal muscular atrophy: Inter and intra-rater reliability and agreement.
The Revised Hammersmith Scale (RHS) for Spinal Muscular Atrophy (SMA) was designed as a psychometrically robust clinical outcome assessment to assess physical abilities of patients with type 2 and 3 SMA. The reliability properties of the RHS have not yet been reported. A prospective RHS reliability study was undertaken in a UK cohort of experienced neuromuscular paediatric Physiotherapists. Reliability testing was conducted via a virtual survey platform two weeks apart. Through the virtual platform participants scored videos of two RHS assessments, one of a child with SMA 2 and one of a child with SMA 3. Inter and intra-rater reliability was analysed using a type 3 Intraclass Correlation Coefficient (ICC). Intra-rater agreement was further analysed using Bland Altman (BA) Limits of Agreement (LOA) and plots. The acceptable inter and intra-rater variability was set as a change of ± 2 by the international team of expert physiotherapists who developed the RHS. Inter-rater agreement, n = 22 raters, type 3 ICC was 0.989 (95% CI 0.944 to 1.00), 97.7% of scores were within the acceptable limits of ± 2 points. Intra-rater agreement, n = 21 raters, type 3 ICC ranged from 0.922 to 1.0, with 97.6% of scores within the acceptable limits of ± 2 points. The mean SMA 2 intra-rater difference was -0.10 (-0.6 to 0.4), with lower LOA -2.24 and upper LOA +2.04. Intra-rater difference between tests for SMA 3 intra-rater difference was -0.05 (-0.6 to 0.5), with lower LOA -2.48 and upper LOA +2.38. Intra-rater scoring precision fell within BA agreement limits of ±2 points. The results demonstrate that the RHS is highly reliable when used by experienced UK physiotherapists, and variability of test scores regarding inter and intra-rater reliability was confirmed to lie within ±2 points.


Dehydrogenase patterns in the taxonomy of Bacteroides.
The malate dehydrogenase (MDH) electrophoretic mobilities of 128 strains of bacteroides belonging to 17 species, including three subspecies of Bacteroides melaninogenicus and two subspecies of Bacteroides ruminicola, were examined. Amongst the pigmented bacteroides, the migration of this enzyme correlated well with recognized taxa, and only one strain, VPI 9085 was clearly different. Other species such as B. oralis, B. buccalis, B. denticola, B. pentosaceus, B. bivius, B. disiens and B. ruminicola were delineated by the combined use of MDH and glutamate dehydrogenase. Forty-three strains belonging to the 'B. fragilis group' differed from the above species in possessing glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, and reference strains as well as fresh isolates were assigned to the correct species by the mobility pattern of these two enzymes. Other properties of MDH such as the pH optima for the oxidation of malate or the reduction of oxaloacetate were of limited taxonomic value. However, the alkaline stability of this enzyme at pH 9, 10 and 11 clearly differentiates the saccharolytic from the non-saccharolytic species of pigmented bacteroides with the latter showing highly stable enzymes with a half life greater than 50 min.


[Morpho-functional changes of surfactant system in pulmonary tuberculosis].
A complex study of different cellular and extracellular surfactant elements in the dynamics of the spontaneous course of generalized tuberculosis was made in 240 guinea-pigs and 77 patients with different forms of active pulmonary tuberculosis by using electron microscopy, biochemistry, and physical chemistry. A diagnostic scheme was proposed for life-time assessment of surfactant in bronchoalveolar lavage specimens. Three degrees of changes in surfactant were identified; 1) adaptive rearrangement of its elements developing in local surfactant damages; 2) significantly impaired type 2 alveolocyte production of surfactant, which affects its biochemical composition and capacity of forming characteristic structures; 3) common morphological, biochemical, surface-active signs of surfactant decompensation, profound metabolic disturbances, alveolar epithelial destruction with cleared alveolocytes found in the lavage.


Detection of ATM gene mutation in human glioma cell line M059J by a rapid frameshift/stop codon assay in yeast.
A yeast-based frameshift/stop codon assay for examining ATM (ataxia telangiectasia mutated) mutations was established. Each of six fragments of a PCR-amplified coding sequence for ATM is inserted in frame by homologous recombination into a yeast URA3 fusion protein gene, and the transformants are assayed for growth in the absence of uracil. The usefulness of this assay was verified in a panel of cell lines derived from individuals with homozygous and heterozygous ATM mutations. The assay was also shown to distinguish between specimens with wild-type alleles and those with truncating mutations: a frameshift mutation or an inserted stop codon. Using this assay M059J cells, which fail to express the catalytic subunit of DNA-dependent protein kinase (PRKDC, also known as DNA-PKcs) and are hypersensitive to ionizing radiation, were found to express two different aberrant ATM transcripts: one characterized by 4776 del 133, which corresponds to the deletion of exon 33, and the other by 4909 ins 116. Subsequent analysis of the intron sequences revealed that 4909 ins 116 is comprised of a nucleotide sequence corresponding to 84013-84128 in intron 33 with a cryptic splice site. Thus the radiosensitive phenotype of M059J cells appears to be due to a defect in PRKDC and a truncating ATM mutation.


[Acupuncture and bronchial asthma].
The 66 randomized patients with mild bronchial asthma who took part in this study were divided into three nearly equal groups. Group one was treated with true acupuncture during the first and the fourth month (up to week 16). Group two was treated similarly but needled at non-acupuncture points. The third group served as a control. All patients were allowed to maintain their normal asthma medication with the recommendation to keep the regimen unchanged until week 20, i. e. 4 weeks after termination of the specific treatment. The changes in peak flow variability up to week 16 served as main outcome criterion. Additional parameters included several spirometric analyses as well as various markers in blood and sputum that are specific for the allergic inflammatory reaction of the upper respiratory tract. The values measured showed considerable individual variability. This impeded the demonstration of efficacy. In conclusion it can be stated that there was a consistent, positive yet unspecified effect of the needling in both treated groups which can be interpreted as a trend in affecting the asthmatic condition. This effect could have been more pronounced or even clinically relevant for certain individuals had one considered a separate analysis of the data of each patient.


Variability in aggressiveness of rice blast (Magnaporthe oryzae) isolates originating from rice leaves and necks: a case of pathogen specialization?
Rice blast, caused by Magnaporthe oryzae, causes yield losses associated with injuries on leaves and necks, the latter being in general far more important than the former. Many questions remain on the relationships between leaf and neck blast, including questions related to the population biology of the pathogen. Our objective was to test the hypothesis of adaptation of M. oryzae isolates to the type of organ they infect. To that aim, the components of aggressiveness of isolates originating from leaves and necks were measured. Infection efficiency, latent period, sporulation intensity, and lesion size were measured on both leaves and necks. Univariate and multivariate analyses indicated that isolates originating from leaves were less aggressive than isolates originating from necks, when aggressiveness components were measured on leaves as well as on necks, indicating that there is no specialization within the pathogen population with respect to the type of organ infected. This result suggests that the more aggressive isolates involved in epidemics on leaves during the vegetative stage of the crop cycle have a higher probability to infect necks, and that a population shift may occur during disease transmission from leaves to necks. Implications for disease management are discussed.


Rapid analysis of metagenomic data using signature-based clustering.
Sequencing highly-variable 16S regions is a common and often effective approach to the study of microbial communities, and next-generation sequencing (NGS) technologies provide abundant quantities of data for analysis. However, the speed of existing analysis pipelines may limit our ability to work with these quantities of data. Furthermore, the limited coverage of existing 16S databases may hamper our ability to characterise these communities, particularly in the context of complex or poorly studied environments. In this article we present the SigClust algorithm, a novel clustering method involving the transformation of sequence reads into binary signatures. When compared to other published methods, SigClust yields superior cluster coherence and separation of metagenomic read data, while operating within substantially reduced timeframes. We demonstrate its utility on published Illumina datasets and on a large collection of labelled wound reads sourced from patients in a wound clinic. The temporal analysis is based on tracking the dominant clusters of wound samples over time. The analysis can identify markers of both healing and non-healing wounds in response to treatment. Prominent clusters are found, corresponding to bacterial species known to be associated with unfavourable healing outcomes, including a number of strains of Staphylococcus aureus. SigClust identifies clusters rapidly and supports an improved understanding of the wound microbiome without reliance on a reference database. The results indicate a promising use for a SigClust-based pipeline in wound analysis and prediction, and a possible novel method for wound management and treatment.


Estimation of depth-dependent material properties of biphasic soft tissues through finite element optimization and sensitivity analysis.
A knowledge of material properties of soft tissue, such as articular cartilage, is essential to assess its mechanical function. It is also increasingly more evident that the inhomogeneity of the tissues plays a significant role in its in vivo functioning. Hence, efficient and reliable tools are needed to accurately characterize the inhomogeneity of the soft tissue mechanical properties. The objective of this research is to propose a finite element optimization procedure to determine depth-dependent material properties of articular cartilage by processing experimental data. Cartilage is modeled as a biphasic continuum with a linear elastic solid phase. The optimization method is based on a sensitivity analysis where the sensitivity of the finite element results to a variation in the material properties is analytically evaluated. The elastic modulus and permeability of the tissue are assumed to vary either linearly or quadratically through the thickness of the cartilage layer. After adopting some initial estimates, these material properties are updated iteratively based on their sensitivities to the current results, and the difference between the actual experimental data and computational experimental data. The optimization method has been tested in two common experimental configurations of cartilage and found to be efficient to estimate the material properties.


NAD+, Axonal Maintenance, and Neurological Disease.
Significance: The remarkable geometry of the axon exposes it to unique challenges for survival and maintenance. Axonal degeneration is a feature of peripheral neuropathies, glaucoma, and traumatic brain injury, and an early event in neurodegenerative diseases. Since the discovery of Wallerian degeneration (WD), a molecular program that hijacks nicotinamide adenine dinucleotide (NAD+) metabolism for axonal self-destruction, the complex roles of NAD+ in axonal viability and disease have become research priority. Recent Advances: The discoveries of the protective Wallerian degeneration slow (WldS) and of sterile alpha and TIR motif containing 1 (SARM1) activation as the main instructive signal for WD have shed new light on the regulatory role of NAD+ in axonal degeneration in a growing number of neurological diseases. SARM1 has been characterized as a NAD+ hydrolase and sensor of NAD+ metabolism. The discovery of regulators of nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) proteostasis in axons, the allosteric regulation of SARM1 by NAD+ and NMN, and the existence of clinically relevant windows of action of these signals has opened new opportunities for therapeutic interventions, including SARM1 inhibitors and modulators of NAD+ metabolism. Critical Issues: Events upstream and downstream of SARM1 remain unclear. Furthermore, manipulating NAD+ metabolism, an overdetermined process crucial in cell survival, for preventing the degeneration of the injured axon may be difficult and potentially toxic. Future Directions: There is a need for clarification of the distinct roles of NAD+ metabolism in axonal maintenance as contrasted to WD. There is also a need to better understand the role of NAD+ metabolism in axonal endangerment in neuropathies, diseases of the white matter, and the early stages of neurodegenerative diseases of the central nervous system. Antioxid. Redox Signal. 39, 1167-1184.


Catalytic enantioselective amide allylation of isatins and its application in the synthesis of 2-oxindole derivatives spiro-fused to the α-methylene-γ-butyrolactone functionality.
This article is a full account of the work exploring the potential utility of catalytic enantioselective amide allylation of various isatins using indium-based chiral catalysts. A survey of various isatin substrates and NH-containing stannylated reagents revealed that the reaction has a remarkably wide scope to result in extremely high yields and enantioselectivities (up to >99 %, 99 % ee) of variously substituted homoallylic alcohols. Several mechanistic investigations demonstrated that the substrate-reagent hydrogen-bond interaction plays a critical role in the formation of the key transition states to result in enhanced catalytic reaction. The success of this approach allowed convenient access to chiral 2-oxindoles spiro-fused to the α-methylene-γ-butyrolactone functionality and their halogenated derivatives in almost enantiopure forms, thus highlighting the general utility of this synthetic method to deliver a large variety of antineoplastic drug candidates and pharmaceutically meaningful compounds.


[Clinico-laboratory basis for the endolymphatic use of beta-lactam antibiotics in pulmonology].
Clinical efficacy and effect of cefuroxime, claforan and pentrexyl used endolymphatically were studied in 85 patients with acute abscess forming and persisting pneumonia. Previous routine antibiotic therapy in these patients was little effective. Administration of the antibiotics into the peripheral lymph nodes provided blocking of the lymphagenic pathway for the infection due to high levels in the lymphatic system. Endolymphatic use of cefuroxime and claforan resulted in a significant improvement of the functions of the T- and B-immunity systems and the indices of natural resistance. The levels of the autoimmune reactions and sensitization to the bacterial antigens decreased. Endolymphatic use of cefuroxime and claforan once every 3 days provided recovery of 9 2.8 per cent of the patients, the treatment periods being decreased 2.5--3 times. Intravenous administration of the drugs according to the routine schemes, endolymphatic use of pentrexyl (5 g once every 3 days) and endolymphatic administration of cefuroxime in a single dose followed by intravenous therapy was less effective. The efficacy of pentrexyl increased, when it was used endolymphatically in combination with lysozyme. Endolymphatic use of claforan in doses of 2--3 g once every 3 days (3--4 infusions during the treatment course) was most effective.


Sexually transmitted diseases knowledge assessment and associated factors among university students in the United Arab Emirates: a cross-sectional study.
Sexually transmitted diseases and infections (STDIs) remain a serious public health menace with over 350 million cases each year. Poor knowledge of STDIs has been identified as one of the bottlenecks in their control and prevention. Hence, assessment of knowledge, both general and domain-specific, is key to the prevention and control of these diseases. This study assessed the knowledge of STDIs and identified factors associated with STDI knowledge among university students in the United Arab Emirates (UAE). This is a cross-sectional study among 778 UAE University students across all colleges. An online data collection tool was used to collect data regarding the participants' demographics and their level of knowledge of STDIs across different domains including general STDI pathogens knowledge (8 items), signs and symptoms (9 items), mode of transmission (5 items), and prevention (5 items). Knowledge was presented both as absolute and percentage scores. Differences in STDI knowledge were statistically assessed using Mann-Whitney U and Chi-squared tests. Logistic regression models were further used to identify factors associated with STDI knowledge. A total of 778 students participated in the study with a median age of 21 years (IQR = 19, 23). The overall median STDI knowledge score of the participants was 7 (out of 27), with some differences within STDI domains-signs & symptoms (1 out of 9), modes of transmission (2 out of 5), general STDI pathogens (2 out of 8), and prevention (1 out of 5). Higher STDI knowledge was significantly associated with being non-Emirati (OR = 1.85, 95% CI = 1.24-2.75), being married (OR = 2.89, 95% CI = 1.50-5.56), residing in emirates other than Abu Dhabi (OR = 1.61, 95% CI = 1.16-2.25), and being a student of health sciences (OR = 4.45, 95% CI = 3.07-6.45). In general, STDI knowledge was low among the students. Having good knowledge of STDIs is essential for their prevention and control. Therefore, there is a need for informed interventions to address the knowledge gap among students, youths, and the general population at large.


A study of fluid dynamics and human physiology factors driving droplet dispersion from a human sneeze.
Recent studies have indicated that COVID-19 is an airborne disease, which has driven conservative social distancing and widescale usage of face coverings. Airborne virus transmission occurs through droplets formed during respiratory events (breathing, speaking, coughing, and sneezing) associated with the airflow through a network of nasal and buccal passages. The airflow interacts with saliva/mucus films where droplets are formed and dispersed, creating a route to transmit SARS-CoV-2. Here, we present a series of numerical simulations to investigate droplet dispersion from a sneeze while varying a series of human physiological factors that can be associated with illness, anatomy, stress condition, and sex of an individual. The model measures the transmission risk utilizing an approximated upper respiratory tract geometry for the following variations: (1) the effect of saliva properties and (2) the effect of geometric features within the buccal/nasal passages. These effects relate to natural human physiological responses to illness, stress, and sex of the host as well as features relating to poor dental health. The results find that the resulting exposure levels are highly dependent on the fluid dynamics that can vary depending on several human factors. For example, a sneeze without flow in the nasal passage (consistent with congestion) yields a 300% rise in the droplet content at 1.83 m (≈6 ft) and an increase over 60% on the spray distance 5 s after the sneeze. Alternatively, when the viscosity of the saliva is increased (consistent with the human response to illness), the number of droplets is both fewer and larger, which leads to an estimated 47% reduction in the transmission risk. These findings yield novel insight into variability in the exposure distance and indicate how physiological factors affect transmissibility rates. Such factors may partly relate to how the immune system of a human has evolved to prevent transmission or be an underlying factor driving superspreading events in the COVID-19 pandemic.


Whole-body pregnant woman modeling by digital geometry processing with detailed uterofetal unit based on medical images.
Anatomical models of pregnant women are used in several applications, such as numerical dosimetry, to assess the potential effects of electromagnetic fields on biological tissues, or medical simulation. Recent advances in medical imaging have enabled the generation of realistic and detailed models of human beings. The construction of pregnant woman models remains a complex task, since it is not possible to acquire whole-body images. Only few models have been developed up to now, and they all present some limitations regarding the representation of anatomical variability of the fetus shape and position over the entire gestation. This paper describes a complete methodology that intends to automate each step of the construction of pregnant women models. The proposed approach relies on the segmentation of 3-D ultrasonic and 3-D magnetic resonance imaging (MRI) data, and on dedicated computer graphics tools. The lack of complete anatomical information for the mother in image data is compensated, in an original way, by merging the available information with a synthetic woman model, deformed to match the image-based information. A set of models anatomically validated by clinical experts is presented. They include detailed information on uterofetal units and cover different gestational stages with various fetal positions.


Evidence of altered brain regulatory gene expression in tobacco-exposed fetuses.
We sought to determine the association between prenatal smoking status and expression of fetal brain regulatory genes. At delivery, we collected information from parturient women on prenatal smoking habits and analyzed salivary cotinine levels. We obtained neonatal umbilical cord blood and extracted total RNA. We then employed the quantitative polymerase chain reaction (QPCR) analyses and the comparative CT method to calculate the relative gene expression of selected fetal brain regulatory genes responsible for (1) brain growth (brain-derived neutrotrophic factor, BDNF), (2) myelination (proteolipidic protein 1, PLP1 and myelin basic protein, MBP), and (3) neuronal migration and cell-cell interactions during fetal brain development or RLN. The χ2-test, analysis of variance (ANOVA), and the Grubb test were used to evaluate the relationship between prenatal smoking status and relative gene expression levels. Further analysis using bootstrapping was performed to assess the precision of our estimates. Of the 39 maternal-infant dyads included in this study, 25.6% were non-smokers, 43.6% were passive smokers and 30.8% were active smokers. The results showed down-regulation of the selected fetal brain regulatory genes among active smokers. These findings represent preliminary evidence in humans that intrauterine tobacco exposure impacts fetal brain programming. Future studies are warranted to examine whether our findings represent potential mechanisms through which adverse childhood/adult-onset cognitive and behavioral outcomes that have been previously linked to intrauterine exposure occur.


Mild cognitive impairment, risk factors and magnetic resonance volumetry: role of probable Alzheimer's disease in the family.
Late-onset Alzheimer's disease (LOAD) comprises sporadic LOAD and familial LOAD. We wanted to determine whether total plasma homocysteine (Hcy), cardiovascular risk factors and volumetric analyses of cerebral magnetic resonance imaging (MRI) were differently associated with mild cognitive impairment (MCI) in subjects from families with aggregation of LOAD (probable familial LOAD) and MCI in subjects from families without LOAD (probable sporadic LOAD). A total of 103 subjects with MCI without known stroke or other apparent causative diseases were included as cases together with 58 controls. The cases were stratified into 3 groups according to the number of biological relatives with probable LOAD on one side of the family. Cerebral MRI was obtained from all. The case groups were compared to the control group in sex-specific analyses of covariance. Hcy was significantly elevated in all cases compared to controls, except for women with probable familial LOAD. These women also had significantly smaller hippocampal volume and significantly larger lateral ventricles, unlike the women in the other case groups. Our findings suggest that research on Hcy, cardiovascular risk factors and other potential risk factors for LOAD might benefit from distinguishing between sporadic and familial LOAD.


Tryptophan Metabolic Pathways and Brain Serotonergic Activity: A Comparative Review.
The essential amino acid L-tryptophan (Trp) is the precursor of the monoaminergic neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Numerous studies have shown that elevated dietary Trp has a suppressive effect on aggressive behavior and post-stress plasma cortisol concentrations in vertebrates, including teleosts. These effects are believed to be mediated by the brain serotonergic system, even though all mechanisms involved are not well understood. The rate of 5-HT biosynthesis is limited by Trp availability, but only in neurons of the hindbrain raphe area predominantly expressing the isoform TPH2 of the enzyme tryptophan hydroxylase (TPH). In the periphery as well as in brain areas expressing TPH1, 5-HT synthesis is probably not restricted by Trp availability. Moreover, there are factors affecting Trp influx to the brain. Among those are acute stress, which, in contrast to long-term stress, may result in an increase in brain Trp availability. The mechanisms behind this stress induced increase in brain Trp concentration are not fully understood but sympathetic activation is likely to play an important role. Studies in mammals show that only a minor fraction of Trp is utilized for 5-HT synthesis whereas a larger fraction of the Trp pool enters the kynurenic pathway. The first stage of this pathway is catalyzed by the hepatic enzyme tryptophan 2,3-dioxygenase (TDO) and the extrahepatic enzyme indoleamine 2,3-dioxygenase (IDO), enzymes that are induced by glucocorticoids and pro-inflammatory cytokines, respectively. Thus, chronic stress and infections can shunt available Trp toward the kynurenic pathway and thereby lower 5-HT synthesis. In accordance with this, dietary fatty acids affecting the pro-inflammatory cytokines has been suggested to affect metabolic fate of Trp. While TDO seems to be conserved by evolution in the vertebrate linage, earlier studies suggested that IDO was only present mammals. However, recent phylogenic studies show that IDO paralogues are present within the whole vertebrate linage, however, their involvement in the immune and stress reaction in teleost fishes remains to be investigated. In this review we summarize the results from previous studies on the effects of dietary Trp supplementation on behavior and neuroendocrinology, focusing on possible mechanisms involved in mediating these effects.


Effects of pulp removal and organ culture on adult rat incisor odontoblasts.
The morphological integrity of adult rat incisor odontoblasts was studied to determine the effects of pulp removal and subsequent incubation. From each pair of maxillary incisors one was left intact while the pulp from the other one was removed. Both series were incubated in BGJb medium according to the Trowell method. Morphometrical measurements of the thickness of the odontoblast layer and the size and shape of the odontoblast nuclei were performed on photomicrographs of transverse sections of the incisors. After pulp removal the odontoblasts seemed disorganized and their nuclei were darker and more rounded. During incubation the odontoblasts did not recover from the effect of this pulp removal and degenerative changes were frequently seen. In the culture of the complete tooth organ the morphological integrity of the odontoblasts was much better preserved. Therefore the organ culture of intact teeth seems more favourable.


2x2 photonic crystal fiber splitter based on silica-based planar lightwave circuits.
A 2x2 photonic crystal fiber (PCF) planar lightwave circuit (PLC) splitter, which splits optical power between two PCF channels, has been made by PCF-to-PLC connections. PCF array blocks were lithographically fabricated to have fiber V grooves and used to firmly hold PCFs and align them to the PLC splitter. The proposed splitter showed a rather flat splitting ratio over a wide wavelength range from 1250 nmto1750 nm. With the implemented splitter, we obtained a low excess loss of 1.6 dB, a low polarization-dependent loss of 0.1 dB, and a high return loss of 52 dB. The ultrabroadband operation of the proposed splitter is expected to find applications in optical performance monitoring, Ethernet passive optical networks, and biomedical optics including optical coherence tomography.


Fournier's syndrome in infants. A review of cases from Ibadan, Nigeria.
Six children aged between 3 and 12 weeks were treated for Fournier's syndrome in our hospital between 1972 and 1979. Circumcision, diaper rash, and perianal skin abscesses were suspected as portals of entry for pathogens initiating the lesions. In two cases Staphylococcus aureus was isolated. Medical treatment of the gangrenous area proved successful in all cases, and the children survived with no appreciable scrotal skin loss or adhesions. Our results confute the approach of previous workers, most of whom have advocated aggressive surgical management in a devastating illness like Fournier's gangrene.


Thermal Inactivation of Listeria monocytogenes in Crab Meat.
Listeria monocytogenes is an important bacterial pathogen in seafood products, but limited information is currently available on the thermal resistance of relevant isolates in seafood. Thermal inactivation studies were undertaken (i) to provide much needed thermal inactivation data for L. monocytogenes in crab meat and (ii) to investigate whether tryptone soya broth (TSB) is representative of crab meat in thermal inactivation studies involving L. monocytogenes. D-values were obtained for a cocktail of two crab isolates (serotypes 1/2a and 4b) at 50, 55, and 60°C. In crab meat, D-values were 174.4, 28.2, and 1.6 min, respectively. Similar D-values of 176.4, 28.8, and 1.4 min were obtained in TSB. The corresponding z-values were 4.9°C (crab meat) and 4.8°C (TSB), respectively. The conclusions were that (i) current pasteurization conditions (e.g., 70°C for 2 min) would achieve complete destruction of any L. monocytogenes present in crab meat and (ii) TSB could be used as a model matrix for assessing the thermal inactivation of L. monocytogenes in crab meat.


Two-stage palatoplasty, is it still a valuable treatment protocol for patients with a cleft of lip, alveolus, and palate?
Speech development is of utmost importance and requires early closure of a palatal cleft. On the other hand, it is well known that all types and timings of surgical repair of facial clefts are detrimental to maxillary growth. Nevertheless, these days one is more and more confronted with a world-wide tendency in favour of the one-in-all operation to close clefts of the lip, alveolus, and palate. Therefore, a three-centre study was performed for testing - once more - the value of two-stage palatoplasty as a means to reduce the detrimental effects of surgery on palatal growth and at the same time to also enable early speech development. Plaster casts from 85 patients have been re-evaluated. All of them had a complete unilateral cleft of lip, alveolus, and palate. They had been treated according to the old therapy protocols followed in either one of the three different cleft centres many years ago, namely in Hamburg, (Western) Germany, Iowa City, IO, USA, and Rostock, (in those days still Eastern) Germany. The impressions had been taken already in 1987 from patients being either 8 years (36 pts.) or 16 years of age (49 pts.). Three different treatment protocols had been followed for these patients in those centres in those days: The main difference was that in centres A and B the palates were closed in two stages whilst in centre C palatoplasty was performed in just one operation. The most interesting results regarding the palatal growth were that: 1. In centre C (one-stage palatoplasty) the patients had more constricted palates. 2. In centre A (two-stage palatoplasty) the patients had least often an anterior cross-bite. It appears that it was possible to show once more that closing the palate in one stage at age 1 year or less is interfering most with maxillary growth. This study leads us to conclude that two-stage palatoplasty is still a valuable treatment protocol for patients with a complete unilateral cleft of lip, alveolus, and palate, especially as apparently good guidance of speech development can lead to satisfactory speech for cleft patients in whom the hard palate was closed at a later age.


Risk for Newly Diagnosed Diabetes >30 Days After SARS-CoV-2 Infection Among Persons Aged <18 Years - United States, March 1, 2020-June 28, 2021.
The COVID-19 pandemic has disproportionately affected people with diabetes, who are at increased risk of severe COVID-19.* Increases in the number of type 1 diabetes diagnoses (1,2) and increased frequency and severity of diabetic ketoacidosis (DKA) at the time of diabetes diagnosis (3) have been reported in European pediatric populations during the COVID-19 pandemic. In adults, diabetes might be a long-term consequence of SARS-CoV-2 infection (4-7). To evaluate the risk for any new diabetes diagnosis (type 1, type 2, or other diabetes) >30 days† after acute infection with SARS-CoV-2 (the virus that causes COVID-19), CDC estimated diabetes incidence among patients aged <18 years (patients) with diagnosed COVID-19 from retrospective cohorts constructed using IQVIA health care claims data from March 1, 2020, through February 26, 2021, and compared it with incidence among patients matched by age and sex 1) who did not receive a COVID-19 diagnosis during the pandemic, or 2) who received a prepandemic non-COVID-19 acute respiratory infection (ARI) diagnosis. Analyses were replicated using a second data source (HealthVerity; March 1, 2020-June 28, 2021) that included patients who had any health care encounter possibly related to COVID-19. Among these patients, diabetes incidence was significantly higher among those with COVID-19 than among those 1) without COVID-19 in both databases (IQVIA: hazard ratio [HR] = 2.66, 95% CI = 1.98-3.56; HealthVerity: HR = 1.31, 95% CI = 1.20-1.44) and 2) with non-COVID-19 ARI in the prepandemic period (IQVIA, HR = 2.16, 95% CI = 1.64-2.86). The observed increased risk for diabetes among persons aged <18 years who had COVID-19 highlights the importance of COVID-19 prevention strategies, including vaccination, for all eligible persons in this age group,§ in addition to chronic disease prevention and management. The mechanism of how SARS-CoV-2 might lead to incident diabetes is likely complex and could differ by type 1 and type 2 diabetes. Monitoring for long-term consequences, including signs of new diabetes, following SARS-CoV-2 infection is important in this age group.


Feasibility of Monotherapy by Rituximab Without Additional Desensitization in ABO-incompatible Living-Donor Liver Transplantation.
Rituximab is a cornerstone in the regimens of desensitization for ABO-incompatible living-donor liver transplantation (ABO-i LDLT) that makes this modality an acceptable option for liver transplantation. Plasmapheresis (PP) to reduce anti-ABO antibody titer and local infusion (LI) therapy were practiced as the strategies for desensitization before the application of rituximab and were reported as additional treatments. The aim of this study was to clarify the feasibility of monotherapy by rituximab without any additional desensitization treatments in ABO-i LT. Forty patients receiving ABO-i LDLT with rituximab were enrolled in this retrospective study. The patients were divided into 2 groups: the rituximab with pretransplant PP and posttransplant LI (RPL) group (n = 20) and the rituximab monotherapy (RM) without any additional treatment group (n = 20). The groups were then compared in terms of the rates of patient survival, antibody-mediated rejection (AMR), and infection. The 1-, 3-, and 5-year patient survival rates were 85%, 85%, and 85% in the RPL group and 89%, 80%, and 80% in the RM group, respectively. There was no significant difference in patient survival between the 2 groups. There were no episodes of AMR in either group. The RM group had a lower rate of fungal and viral infections than the RPL group. Pretransplant rituximab without additional treatments yielded satisfactory outcomes comparable to that with additional treatments, such as PP and LI.


[Use of levamisole in W. bancrofti filariasis].
16 african patients with diagnosed W. bancroft's filariasis admitted to Pedro Kourí Tropical Medicine Institute were subjected to a therapeutic management with levamisole: 300 mg as starting dosage, and 150 mg/day for seven days. 11 patients had been previously treated with several courses of diethylcarbamazine (DEC), but a low microfilaremia persisted in them. In the other 5 patients the only medication used was levamisole. A rapid fall in microfilaria concentrations was found from the first day of treatment on in all patients. Eventually, 14 patients (87,5%) were negative and two patients (12,5%) persisted having low microfilaremia and their concentrations lowered by 89 ad 93% respectively.


Multifunctional polyurethane sponge for polymerase chain reaction enhancement.
Selective filtering of target biomaterials from impurities is an important task in DNA amplification through polymerase chain reaction (PCR) enhancement and gene identification to save endangered animals and marine species. Conventional gene extraction methods require complicated steps, skilled persons, and expensive chemicals and instruments to improve DNA amplification. Herein, we proposed an alternative method for overcoming such challenges by imparting secondary functionality using commercially available polyurethane (PU) sponges and cost-effective fabrication approaches through polydopamine and polysiloxane coatings. The porous, highly flexible, and chemically modified superhydrophilic and superhydrophobic PU sponges allow large surface areas and mechanically stable frames for effective extraction of genomic DNA through selective filtering of fish tissues and oils. Furthermore, these chemically modified PU sponges allow separation of genes and improvement of PCR for DNA amplification for the identification of fish species. The combination of a simple fabrication method and functionalized PU sponges could be a useful platform for PCR enhancement and gene-based identification of species for practical applications.


Interaction between insulin (VNTR) and hepatic lipase (LIPC-514C>T) variants on the response to an oral glucose tolerance test in the EARSII group of young healthy men.
Insulin resistance is polygenic in origin, and can be observed at an early age. We have shown that variations in APOC3-482T>C and hepatic lipase (LIPC)-514C>T), individually (APOC3 alone) and interactively, modulate insulin and glucose levels after an OGTT in young healthy men participating in the European Atherosclerosis Research Study II (EARSII). Variation in the insulin gene (INS) variable number tandem repeat (VNTR) has been found to predispose to type 1 and type 2 diabetes. We have evaluated the HphI site 23 bp upstream of the INS gene (a surrogate marker for the VNTR) in EARSII (n=822), to determine if variation in INS contributes to insulin resistance. Carriers of the INS VNTR class III (HphI-) allele (frequency=0.29 (95%CI 0.27, 0.31)) had significantly higher 60-min insulin concentrations after the OGTT (P=0.014) and a marginally higher AUC insulin (P=0.07), compared to class I (HphI+) homozygotes. However, this effect on AUC insulin was modified by the level of physical activity, displaying significant gene:environment interaction (P=0.03). We tested for gene:gene interaction between the INS VNTR and both the LIPC-514C>T and APOC3-482T>C. While there was a significant interaction between INS VNTR and LIPC-514C>T on AUC glucose (P=0.013) and on AUC insulin (P=0.015), there was no interaction with APOC3-482T>C. Thus, despite a modest effect of the INS VNTR alone, the influence of this variant on insulin sensitivity was modified by gene:environment and gene:gene interactions, illustrating the biological complexity of insulin resistance.


Efficacy of olanzapine monotherapy in acute bipolar depression: a pooled analysis of controlled studies.
The efficacy and safety of olanzapine monotherapy in bipolar depression has been evaluated in 2 placebo-controlled studies. We pooled data from 2 previously published studies examining olanzapine monotherapy in patients with bipolar I depression. Changes from baseline to 6 weeks in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, MADRS-6 (included items: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts) score, and individual MADRS item scores were assessed with an analysis of variance (ANOVA) model. Influence of patient baseline characteristics (age, gender, MADRS total score, age at onset of bipolar disorder, psychotic features, melancholic feature, mixed features [≥2 on ≥3 Young Mania Rating Scale items], and racial origin) on the efficacy of olanzapine monotherapy was examined with an ANOVA model for each factor and stepwise multiple regression analysis. Included were a total of 690 olanzapine-group and 524 placebo-group patients. MADRS total, MADRS-6, and all individual MADRS item scores (except concentration difficulties and suicidal thoughts) showed significantly (P≤0.05) greater decreases from baseline to 6 weeks in olanzapine-treated patients than those on placebo. The only baseline characteristic associated with response to olanzapine was melancholic feature. The study was limited by omission of patients with bipolar II disorder, post hoc analysis of data from only two clinical trials, and exclusion of suicidal patients. Olanzapine monotherapy improved core symptoms of depression in patients with bipolar I depression. Additionally, we identified melancholic feature as a baseline factor associated with improved treatment response to olanzapine.


Tad and toxin-coregulated pilus structures reveal unexpected diversity in bacterial type IV pili.
Type IV pili (T4P) are ubiquitous in both bacteria and archaea. They are polymers of the major pilin protein, which has an extended and protruding N-terminal helix, α1, and a globular C-terminal domain. Cryo-EM structures have revealed key differences between the bacterial and archaeal T4P in their C-terminal domain structure and in the packing and continuity of α1. This segment forms a continuous α-helix in archaeal T4P but is partially melted in all published bacterial T4P structures due to a conserved helix breaking proline at position 22. The tad (tight adhesion) T4P are found in both bacteria and archaea and are thought to have been acquired by bacteria through horizontal transfer from archaea. Tad pilins are unique among the T4 pilins, being only 40 to 60 residues in length and entirely lacking a C-terminal domain. They also lack the Pro22 found in all high-resolution bacterial T4P structures. We show using cryo-EM that the bacterial tad pilus from Caulobacter crescentus is composed of continuous helical subunits that, like the archaeal pilins, lack the melted portion seen in other bacterial T4P and share the packing arrangement of the archaeal T4P. We further show that a bacterial T4P, the Vibrio cholerae toxin coregulated pilus, which lacks Pro22 but is not in the tad family, has a continuous N-terminal α-helix, yet its α1 s are arranged similar to those in other bacterial T4P. Our results highlight the role of Pro22 in helix melting and support an evolutionary relationship between tad and archaeal T4P.


Why resident duty hours regulations must address attending physicians' workload.
For much of the past decade, the duty hours debate has focused primarily on the intended and unintended effects of resident duty hours restrictions on resident well-being and fatigue, patient safety, discontinuity and handoffs, and opportunities for teaching. On the other hand, attending physicians' needs and perspectives generally have been ignored. The authors of this commentary discuss the report by Roshetsky and colleagues in this issue of Academic Medicine, which found that attending physicians reported a greater clinical workload since the implementation of the 2003 Accreditation Council for Graduate Medical Education resident duty hours regulations, and that this increase in attending physicians' workload appears to correlate with decreased time for teaching. However, attending physicians not having time to teach may be but the tip of the iceberg. Other potential implications include faculty members' decreased availability for direct supervision of residents, their reduced emphasis on resident assessment, and their burnout and dissatisfaction, which ultimately also negatively affect patient care. Therefore, deliberate efforts to address attending physicians' workload must receive greater attention if the duty hours movement is to achieve its ultimate goal of improving patient outcomes. In this commentary, the authors advocate that duty hours regulations require programs to seek creative solutions to address these issues, just as the 2011 regulations require programs to address patient handoff training.


The contribution of the swallowed fraction of an inhaled dose of salmeterol to it systemic effects.
Salmeterol is approximately eight times as potent as salbutamol for systemic effects. This may be because the drug is eight times more potent on receptors or there may be differences in systemic bioavailability. The systemic effects of salbutamol are limited by its fairly high first-pass metabolism, but the oral bioavailability of salmeterol is unknown. The contribution of the swallowed fraction of an inhaled dose of salmeterol to its systemic effects were analysed in a randomized, double-blind, crossover study. Twelve healthy subjects were given inhaled salmeterol 400 microg, inhaled salmeterol 400 microg plus oral activated charcoal or inhaled placebo plus oral activated charcoal on three separate days. Cardiac frequency (fC), Q-T interval corrected for heart rate (QTc), plasma potassium and glucose concentrations were measured for 4 h following the inhaled drug. Salmeterol with and without oral charcoal produced significant changes for all measures compared to placebo. The magnitude of effect following salmeterol alone was significantly greater than that following salmeterol plus charcoal for fC and glucose (mean (95% confidence interval) differences 8 (2-13) beats x min(-1), 0.59 (0.04, 1.13) mmol x L(-1), respectively) and nonsignificantly greater for QTc interval and potassium concentration. The differences between salmeterol given with and without charcoal suggest that 28-36% of the systemic response to salmeterol administered from a metered-dose inhaler are due to drug absorbed from the gastrointestinal tract. Thus, most of the systemic effects are due to the inhaled fraction of the drug.


Age-adjusted Charlson Comorbidity Index as a prognostic factor for radical prostatectomy outcomes of very high-risk prostate cancer patients.
Prostate cancer (PC) is a devastating and heterogeneous condition with diverse treatment options. When selecting treatments for patients with very high-risk PC, clinicians must consider patient comorbidities. We investigated the efficacy of the age-adjusted Charlson Comorbidity Index (ACCI) as a prognostic factor for patient outcomes after radical prostatectomy (RP). We retrospectively investigated the medical records of PC patients at our institution who underwent RP from 1992 to 2010. Very high-risk PC was defined according to National Comprehensive Cancer Network guidelines. Patients with incomplete medical records or who had received neoadjuvant therapy were excluded. Preoperative comorbidity was evaluated by the ACCI, and the prognostic efficacy of the ACCI was analyzed using univariable and multivariable Cox regression, competing risk regression model and Kaplan-Meier curves. Our final analysis included 228 men with a median age of 66 years (interquartile range 62-71) and median prostate specific antigen of 10.7 ng/mL. There were 41 (18%) patients with an ACCI score >3 and 88 (38.6%) patients with a biopsy Gleason score >8. Preoperative evaluation revealed that 159 patients (69.7%) had a non-organ confined tumor (≥T3). Following RP, 8-year prostate cancer-specific survival (PCSS) and overall survival (OS) rates were 91.6% and 83.4%, respectively. Competing risk regression analysis revealed that ACCI was significantly associated with other-cause survival and OS (p<0.05). The ACCI is an effective prognostic factor for other-cause survival and OS in very high-risk PC patients. RP should be considered carefully for patients with an ACCI score >3.


Reduction of patient exposure in pediatric radiology.
The authors determined whether presently used exposure levels in pediatric imaging can be reduced without loss of information or a decrease in diagnostic accuracy. Multiple (stacked) image detectors and filters were used to obtain identical compute radiographic images at different exposure levels of neonates with either no active lung disease or hyaline membrane disease. Physical characteristics of the images were measured. A contrast-detail study and a receiver operating characteristic study were conducted to measure observer performance. Physical measurements and results of the contrast-detail study revealed that the dose-reduction images were essentially limited by x-ray quantum noise. Results of the receiver operating characteristic study indicated that diagnostic accuracy did not decrease significantly up to about 75% exposure reduction levels, although image quality rating data decreased with each exposure reduction. Decreasing exposure levels to about 75% of current levels may be acceptable in some clinical situations where dose is a concern, such as in pediatric imaging.


Imaging of the salivary glands.
Salivary gland diseases are very common disorders and require radiologic evaluation. Several radiologic methods are used for assessment of these diseases. Conventional films of the parotid and submandibular glands demonstrate opaque stones in the duct system, whereas sialography depicts nonopaque stones, provides additional information on the position of the stones, and differentiates it from other calcific densities near the duct system, as well as providing information concerning ectasia of the ducts. CT has been used for evaluating mass lesions and extraglandular inflammatory disease, including abscesses. CT also depicts stones that may not be visible on conventional films. MR imaging has become an important modality in the diagnosis and definition of benign and malignant tumors and cysts and it will probably replace CT as the primary imaging modality for the assessment of these lesions. Gadolinium may be used in the examination, especially if a malignant tumor is suspected (because of irregularity and intraglandular extension).


Mathematical modelling and control of schistosomiasis in Hubei Province, China.
Hubei Province, along with four other provinces in the central and eastern China where schistosomiasis is endemic (Anhui, Hunan, Jiangsu, and Jiangxi), is located in the lake and marshland regions along the Yangtze River. High population density, large numbers of farm cattle, and huge areas of snail habitat are the main characteristics that maintain the persistence of the disease and the transmission of the parasite Schistosoma japonicum in these regions. Based on the schistosomiasis infection data from Hubei province, we propose a mathematical model for the human-cattle-snail transmission of schistosomiasis. The model is a system consisting of six ordinary differential equations that describe susceptible and infected human, cattle and snail subpopulations. After analyzing the existence of the disease-free equilibrium of the model, we determine the basic reproduction number and use the model to simulate the schistosomiasis infection data from Hubei Province. By carrying out sensitivity analyses of the basic reproduction number on various parameters, we find that the transmission of S. japonicum between cattle and snails plays a more important role than that between humans and snails in the endemicity of schistosomiasis in these regions. This strongly suggests that, to control and eventually eradicate schistosomiasis in the lake and marshland regions in China, a more comprehensive approach needs to include environmental factors in order to break the cattle-snail transmission cycle.


Reduced cholesteryl ester transfer in plasma of patients with lipoprotein lipase deficiency.
The net mass transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to the apolipoprotein (apo) B-containing lipoproteins, very low density lipoprotein (VLDL) and low density lipoprotein (LDL) in plasma (cholesteryl ester transfer (CET)) from three patients lacking lipoprotein lipase (LpL) activity was significantly lower (P < 0.001) than in plasma from fasting control subjects with comparable triglyceride levels. Chylomicrons isolated from LpL-deficient fasting plasma showed the same low level of CET activity as observed in the intact plasma when combined with HDL and cholesteryl ester transfer protein (CETP)-containing d 1.063 g/ml bottom fractions from control subjects. Preincubation of chylomicrons and large triglyceride-rich lipoproteins (Sf > 400) from LpL-deficient plasma with milk LpL, however, stimulated the capacity to engage in CET 4- to 5-fold to the same level as chylomicrons and VLDL from control subjects after a fat load. Consistent with these measurements of CET activity in plasma, chylomicrons obtained from the LpL-deficient subjects after a 14-h fast had higher TG/CE ratios than chylomicrons from controls 3 h after ingesting a fat load (LpL-deficient 26.3 +/- 9.0 vs. controls 6.9 +/- 2.1; mean +/- SD). The mass of CETP did not differ in LpL-deficient and control subjects (LpL-deficient 1.03 +/- 0.22 micrograms/ml vs. controls 1.58 +/- 0.58 micrograms/ml). These studies are consistent with earlier in vitro studies showing that the actions of lipoprotein lipase and its lipolytic products are essential, for maximal cholesteryl ester transfer protein activity.


Oxidative injury and antioxidants in coronary artery bypass graft surgery: off-pump CABG significantly reduces oxidative stress.
Coronary artery bypass grafting (CABG) can now be performed with or without cardiopulmonary bypass. The former entails global ischemia followed by reperfusion after declamping, whereas the latter does not. In view of growing evidence that reperfusion is associated with oxidative stress, we studied the extent of oxidative stress and antioxidant status in patients undergoing on-pump and off-pump CABG to determine whether the latter significantly reduces oxidative stress. Thirty patients were initially enrolled for the study. The inclusion criteria included patients with atherosclerotic triple vessel disease, undergoing elective CABG, with good LV function, no major risk factors for surgery, with all biochemical investigations within normal limits, having stable angina and no history of previous infarct. Patients with valvular heart disease, ventricular aneurysm, heart failure and poor left ventricular function were excluded. These were alternately posted for on-pump and off-pump CABG. Eight patients were excluded as they developed unforeseen complications during the surgery. Out of the remaining 22 patients, 13 underwent off-pump CABG and 9 underwent on-pump CABG. Five blood samples were collected; baseline, 5, 15, 60 min and 24 h after reperfusion. Samples were analyzed for thiobarbituric acid reactive substances (TBARS), glutathione (G-SH) and catalase (CAT). The results were compared with their preanaesthetic levels in both the groups and also with 20 age- and sex-matched normal healthy individuals. Lipid peroxidation was significantly increased after reperfusion in patients undergoing on-pump CABG, maximum increase (p<0.0001) was seen 1 h after reperfusion, whereas off-pump CABG reduces oxidative stress. The G-SH levels were significantly decreased after reperfusion in on-pump and off-pump CABG patients, maximum decrease (p<0.0001) was seen 5 min after reperfusion in on-pump CABG. The catalase activity was significantly increased after reperfusion in on-pump and off-pump CABG patients, maximum increase (p<0.0001) was seen 1 h after reperfusion in on-pump CABG. Significant increase in oxidative stress was seen in patients undergoing on-pump CABG, whereas oxidative stress was less in off-pump CABG patients. The G-SH levels were decreased and Catalase activity was increased significantly in both on-pump and off-pump CABG patients.


Color-based tumor tissue segmentation for the automated estimation of oral cancer parameters.
This article presents an automatic color-based feature extraction system for parameter estimation of oral cancer from optical microscopic images. The system first reduces image-to-image variations by means of color normalization. We then construct a database which consists of typical cancer images. The color parameters extracted from this database are then used in automated online sampling from oral cancer images. Principal component analysis is subsequently used to divide the color features into four tissue types. Each pixel in the cancer image is then classified into the corresponding tissue types based on the Mahalanobis distance. The aforementioned procedures are all fully automated; in particular, the automated sampling step greatly reduces the need for intensive labor in manual sampling and training. Experiments reveal high levels of consistency among the results achieved using the manual, semiautomatic, and fully automatic methods. Parameter comparisons between the four cancer stages are conducted, and only the mean parameters between early and late cancer stages are statistically different. In summary, the proposed system provides a useful and convenient tool for automatic segmentation and evaluation for stained biopsy samples of oral cancer. This tool can also be modified and applied to other tissue images with similar staining conditions.


Comparison of two isozymes of carbonic anhydrase in the rat anterior pituitary gland and pituitary tumors.
Two isozymes of carbonic anhydrase (EC 18.104.22.168.) were compared in the anterior pituitary gland of non-tumor-bearing rats and in the hormone-secreting pituitary tumors. In contrast to the pituitary gland, which contained 60 to 70% of the total carbonic anhydrase in the particulate subcellular fraction, three hormone-secreting pituitary tumors were devoid of the particulate (Triton X-100-solubilized)enzyme activity. Another pituitary tumor, 7315a, contained particulate carbonic anhydrase, but the activity was only 45% of the activity of normal pituitary gland. During the development of the rat brain, the particulate (Triton X-100-solubilized) carbonic anhydrase activity was undetectable in prepartions up to 21 days of age (body weight, 47 g). After that age, the carbonic anhydrase activity in the particulate fraction increased rapidly and reached the adult level at 37 days (body weight, 120 g), while the activity in the soluble fraction increased gradually after birth and then reached a plateau at 30 days (body weight, 81 g). These data show that the isozyme pattern of carbonic anhydrase in pituitary tumor tissue resembles the pattern in fetal cells more than the pattern in adult tissue.


Mycobacterium gordonae Skin Infection in an Immunocompetent Child.
Mycobacterium gordonae is a slow growing, pigmented, nontuberculous mycobacterium. It is commonly associated with environmental contamination of clinical specimens, but it is also a recognized pathogen in immunocompromised hosts. We describe an immunocompetent child with a spontaneously occurring skin ulcer on the face caused by M. gordonae infection.


Localization of aldosterone-producing adrenocortical adenomas: significance of adrenal venous sampling.
Accurate localization of aldosterone-producing adenoma (APA) is essential for the treatment of primary aldosteronism (PA). In order to confirm the clinical usefulness of adrenal venous sampling (AVS), we retrospectively studied 87 cases of PA in whom AVS was conducted. We collected right and left adrenal venous effluents simultaneously before and after adrenocorticotropic hormone (ACTH) stimulation for measurements of aldosterone concentration (A) and cortisol concentration (C). Based on AVS results, we judged 66 cases as having unilateral aldosterone hypersecretion and the remaining 21 cases as having no apparent laterality. Of the above 66 subjects, 61 underwent laparoscopic removal of the adrenal gland through a retroperitoneal approach. The presence of APA was histopathologically confirmed, and blood pressure decreased significantly with normalization of plasma aldosterone concentration (PAC) in all cases. The receiver operator characteristics (ROC) curve analysis between the operated and no-apparent-laterality groups revealed that the ratio of A/C on the higher side to A/C on the lower side (A/C ratio) after ACTH stimulation is a useful index, with a cutoff value of 2.6, a sensitivity of 0.98 and a specificity of 1.0. The ROC curve analysis between the APA side and contralateral side within the operated patients revealed that the cutoff value of A was 1,340 ng/dL, with a sensitivity of 0.92 and a specificity of 1.00. Our results indicate the usefulness of simultaneous AVS and ACTH stimulation for localizing APA.