The role of mannose binding lectin on fever episodes in pediatric oncology patients.
Despite significant changes in pediatric oncological therapy, mortality is still high, mainly due to infections. Complement system as an ancient immune defense against microorganisms plays a significant role in surmounting infections, therefore, deficiency of its components may have particular importance in malignancies. The present paper assesses the effect of promoter (X/Y) and exon 1 (A/0) polymorphisms of the MBL2 gene altering mannose binding lectin (MBL) serum level in pediatric oncological patients with febrile neutropenia. Furthermore, frequency distribution of MBL2 alleles in children with malignancies and age-matched controls was analysed. Fifty-four oncohematological patients and 53 children who had undergone pediatric surgery were enrolled into this retrospective study. No significant differences were found in the frequency of MBL2 alleles between the hemato-oncologic and control group. The average duration of fever episodes was significantly shorter (p = 0.035) in patients carrying genotypes (AY/AY and AY/AX) that encode normal MBL level, compared to individuals with genotypes associated with lower functional MBL level (AX/AX, AY/0, AX/0, or 0/0) (days, median (IQ range) 3.7(0-5.4) vs. 5.0(3.8-6.6), respectively). In conclusion, our data suggest that MBL2 genotypes may influence the course of febrile neutropenia in pediatric patients with malignancies, and may contribute to clarification of the importance of MBL in infections.


Neural responses to natural and enhanced speech edges in children with and without dyslexia.
Sensory-neural studies indicate that children with developmental dyslexia show impairments in processing acoustic speech envelope information. Prior studies suggest that this arises in part from reduced sensory sensitivity to amplitude rise times (ARTs or speech "edges") in the envelope, accompanied by less accurate neural encoding of low-frequency envelope information. Accordingly, enhancing these characteristics of the speech envelope may enhance neural speech processing in children with dyslexia. Here we applied an envelope modulation enhancement (EME) algorithm to a 10-min story read in child-directed speech (CDS), enhancing ARTs and also enhancing low-frequency envelope information. We compared neural speech processing (as measured using MEG) for the EME story with the same story read in natural CDS for 9-year-old children with and without dyslexia. The EME story affected neural processing in the power domain for children with dyslexia, particularly in the delta band (0.5-4 Hz) in the superior temporal gyrus. This may suggest that prolonged experience with EME speech could ameliorate some of the impairments shown in natural speech processing by children with dyslexia.


Underlying factors in the association between depressed mood and mobility limitation in older people.
Depressed mood may either precede mobility limitation or follow from mobility limitation. To compare mood status among people with manifest mobility limitation, those with preclinical mobility limitation and those without mobility limitation and investigate factors explaining the association between depressed mood and mobility limitation. Cross-sectional. 645 community-living 75- to 81-year-old people. Depressed mood was assessed using the Centre for Epidemiologic Studies Depression Scale (CES-D, cut-off score 16); difficulty walking 500 m was assessed by self-report. Those reporting difficulty were categorised as having manifest mobility limitation. Those with no difficulty but reporting task modifications, such as reduced frequency of walking, were categorised as having preclinical mobility limitation. The association between depressed mood and mobility limitation was analysed using logistic regression analysis with gender, age, economic situation, the availability of a confidant, chronic conditions, and widespread pain as covariates. Depressed mood was found in 34% of subjects with manifest mobility limitation, in 26% of those with preclinical mobility limitation, and in 13% of those without mobility limitation. The unadjusted odds ratio for depressed mood was 3.43 (95% CI 2.04-5.76) among subjects with manifest mobility limitation and 2.38 (95% CI 1.52-3.73) among those with preclinical mobility limitation, compared to those without mobility limitation. Adjustment for covariates reduced the risks to 2.10 (95% CI 1.15-3.82) and 1.99 (95% CI 1.24-3.20), respectively. Widespread pain explained 28% of the increased risk of depressed mood among those with manifest mobility limitation. The dose-response relationship between depressed mood and mobility limitation suggests that both conditions may progress simultaneously and may share aetiology, at least in part. Pain may be an underlying factor in both depressed mood and mobility limitation.


Surgery for recurrent peptic ulceration.
Sixty-six patients having surgery for recurrent peptic ulcers over a 10-year period are reviewed. The majority of the patients were male and developed their initial ulcers at an early age. Bleeding was the most common presenting symptom. Seventy-one percent of the recurrences occurred within three years. Barium meal X-ray examination plus endoscopy gave the correct diagnosis in 96% of cases. The causes of the recurrent peptic ulcers were: (1) incomplete vagotomy; (2) inadequate gastric resection; (3) inappropriate surgery; (4) Zollinger-Ellison syndrome; (5) gastric outflow obstruction; and (6) bile reflux. Other factors such as alcohol, analgesic abuse and psychiatric disorders were found to be common associations. Resection plus vagotomy was the summation of primary and secondary surgery in 85%. The operative mortality was 3%. Eighty-five percent of patients had a Visick grading of I or II. Only one patient had a further recurrent ulcer and this healed on medical treatment.


The nematocyst's sting is driven by the tubule moving front.
The nematocyst is the explosive injection system of the phylum Cnidaria, and is one of the fastest delivery systems found in Nature. Exploring its injection mechanism is key for understanding predator-prey interactions and protection against jellyfish stinging. Here we analyse the injection of jellyfish nematocysts and ask how the build-up of the poly-γ-glutamate (pγGlu) osmotic potential inside the nematocyst drives its discharge. To control the osmotic potential, we used a two-channel microfluidic system to direct the elongating nematocyst tubule through oil, where no osmotic potential can develop, while keeping the nematocyst capsule in water at all times. In addition, the flow inside the tubule and the pγGlu concentration profiles were calculated by applying a one-dimensional mathematical model. We found that tubule elongation through oil is orders of magnitude slower than through water and that the injection rate of the nematocyst content is reduced. These results imply that the capsule's osmotic potential is not sufficient to drive the tubule beyond the initial stage. Our proposed model shows that the tubule is pulled by the high osmotic potential that develops at the tubule moving front. This new understanding is vital for future development of nematocyst-based systems such as osmotic nanotubes and transdermal drug delivery.


Neuropsychiatric complications in a patient with Marfan syndrome.
Marfan syndrome (MFS) is an autosomal dominant disorder of fibrillin-1 gene mutations, with the involvement of cardiovascular, skeletal, and ocular systems. In addition to physical abnormalities, MFS patients are also found to be susceptible to schizophrenia and other psychiatric conditions. Awareness of the association between MFS and psychiatric conditions would improve the clinical management of MFS patients to reduce the risk or even to prevent the development of psychiatric complications in MFS patients. Here, we describe a male MFS patient who manifested incoherent speech and impaired cognitive and social function at the age of 40 years. Results and conclusion His mental dysfunction could be attributed to his bilateral cerebral infarction, which is a neurovascular complication associated with MFS.


Regional differences of L-type high voltage-gated calcium channel subunit expression in the mouse brain after chronic morphine treatment.
As functional changes in L-type high voltage-gated calcium channels (HVCCs) are recognized to be one of the major neurochemical modifications occurring in brains of animals with morphine physical dependence, this study attempts to examine whether regional difference in the expressions of HVCC subunits are produced in the brains under such pathological conditions. Scatchard analysis of [(3)H]PN200-110 binding showed increased Bmax values in the cerebral cortex and the mesolimbic region including the nucleus accumbence, which are brain regions participating in the development of morphine physical dependence, but not in the cerebellum. In the former two brain regions, alpha1C and alpha1D subunits of L-type HVCCs and alpha2/delta1 subunit increased, although decreases of alpha1B and alpha2/delta1 subunits were observed in the cerebellum. A single dose of morphine did not change the expression of any of the HVCC subunits. These results indicate that the increased L-type HVCC subunits in the cerebral cortex and mesolimbic region participate in the development of morphine physical dependence.


Protective role and related mechanism of Gnaq in neural cells damaged by oxidative stress.
Gnaq is a member of G protein family and is rich in brain tissue. It has attracted the attention of many researchers in melanoma due to its high ratio of mutation. We have previously reported that the expression level of Gnaq in the mouse forebrain cortex was significantly decreased with age. Oxidative stress (OS) is the main cause leading to brain aging and related diseases. The roles and mechanisms of Gnaq in antioxidation in the brain have not been fully explored. In the present study, gene recombinant technique and lentivirus transfection technique were used to generate a Gnaq-overexpression cell model (Gnaq-SY5Y) coupled with H2O2 to build an OS model. The viability of cells, concentration of reactive oxygen species (ROS), apoptosis-related proteins (Bcl-2 and Bax), and signal pathways (NF-κB and Erk1/2) were compared between model cells and control cells. Results showed that the antioxidative ability of Gnaq-SY5Y cells was significantly improved. Concomitantly, the ROS level in Gnaq-SY5Y cells was significantly decreased whether the cells were subject to or not to H2O2 treatment. Anti-apoptotic protein Bcl-2 was up-regulated and apoptosis-promoting protein Bax was down-regulated in Gnaq-SY5Y cells after treatment with H2O2. NF-κB and phosphorylated Erk1/2 (p-Erk1/2) was significantly down-regulated in Gnaq-SY5Y cells. H2O2 treatment decreased Gnaq expression but increased NF-κB and p-Erk1/2 expressions in Gnaq-SY5Y cells. It is therefore concluded that Gnaq plays a pivotal role in antioxidation in neural cells. A possible mechanism for this would be that the overexpressed Gnaq inhibits the cellular damaging effect mediated by NF-κB and Erk1/2 signal pathways.


Idebenone Has Distinct Effects on Mitochondrial Respiration in Cortical Astrocytes Compared to Cortical Neurons Due to Differential NQO1 Activity.
Idebenone is a synthetic quinone that on reduction in cells can bypass mitochondrial Complex I defects by donating electrons to Complex III. The drug is used clinically to treat the Complex I disease Leber's hereditary optic neuropathy (LHON), but has been less successful in clinical trials for other neurodegenerative diseases. NAD(P)H:quinone oxidoreductase 1 (NQO1) appears to be the main intracellular enzyme catalyzing idebenone reduction. However, NQO1 is not universally expressed by cells of the brain. Using primary rat cortical cells pooled from both sexes, we tested the hypotheses that the level of endogenous NQO1 activity limits the ability of neurons, but not astrocytes, to use idebenone as an electron donor to support mitochondrial respiration. We then tested the prediction that NQO1 induction by pharmacological activation of the transcription factor nuclear erythroid 2-related factor 2 (Nrf2) enables idebenone to bypass Complex I in cells with poor NQO1 expression. We found that idebenone stimulated respiration by astrocytes but reduced the respiratory capacity of neurons. Importantly, idebenone supported mitochondrial oxygen consumption in the presence of a Complex I inhibitor in astrocytes but not neurons, and this ability was reversed by inhibiting NQO1. Conversely, recombinant NQO1 delivery to neurons prevented respiratory impairment and conferred Complex I bypass activity. Nrf2 activators failed to increase NQO1 in neurons, but carnosic acid induced NQO1 in COS-7 cells that expressed little endogenous enzyme. Carnosic acid-idebenone combination treatment promoted NQO1-dependent Complex I bypass activity in these cells. Thus, combination drug strategies targeting NQO1 may promote the repurposing of idebenone for additional disorders.SIGNIFICANCE STATEMENT Idebenone is used clinically to treat loss of visual acuity in Leber's hereditary optic neuropathy. Clinical trials for several additional diseases have failed. This study demonstrates a fundamental difference in the way idebenone affects mitochondrial respiration in cortical neurons compared with cortical astrocytes. Cortical neurons are unable to use idebenone as a direct mitochondrial electron donor due to NQO1 deficiency. Our results suggest that idebenone behaves as an NQO1-dependent prodrug, raising the possibility that lack of neuronal NQO1 activity has contributed to the limited efficacy of idebenone in neurodegenerative disease treatment. Combination therapy with drugs able to safely induce NQO1 in neurons, as well as other brain cell types, may be able to unlock the neuroprotective therapeutic potential of idebenone or related quinones.


Partially silencing brain toll-like receptor 4 prevents in part left ventricular remodeling with sympathoinhibition in rats with myocardial infarction-induced heart failure.
Left ventricular (LV) remodeling and activation of sympathetic nervous system (SNS) are cardinal features of heart failure. We previously demonstrated that enhanced central sympathetic outflow is associated with brain toll-like receptor 4 (TLR4) probably mediated by brain angiotensin II type 1 receptor in mice with myocardial infarction (MI)-induced heart failure. The purpose of the present study was to examine whether silencing brain TLR4 could prevent LV remodeling with sympathoinhibition in MI-induced heart failure. MI-induced heart failure model rats were created by ligation of left coronary artery. The expression level of TLR4 in brainstem was significantly higher in MI-induced heart failure treated with intracerebroventricular (ICV) injection of hGAPDH-SiRNA than in sham. TLR4 in brainstem was significantly lower in MI-induced heart failure treated with ICV injection of TLR4-SiRNA than in that treated with ICV injection of hGAPDH-SiRNA. Lung weight, urinary norepinephrine excretion, and LV end-diastolic pressure were significantly lower and LV dimension was significantly smaller in MI-induced heart failure treated with TLR4-SiRNA than in that treated with hGAPDH-SiRNA for 2 weeks. Partially silencing brain TLR4 by ICV injection of TLR4-SiRNA for 2 weeks could in part prevent LV remodeling with sympathoinhibition in rats with MI-induced heart failure. Brain TLR4 has a potential to be a target of the treatment for MI-induced heart failure.


Clinical outcome in patients with prostate cancer treated with external beam radiotherapy and high dose-rate iridium 192 brachytherapy boost: a 6-year follow-up.
To report the long-term results for treatment of localized carcinoma of the prostate using high dose rate (HDR) brachytherapy, conformal external beam radiotherapy (3D EBRT) and neo-adjuvant hormonal therapy (TAB). From 1998 through 1999, 154 patients with localized prostate cancer were entered in the trial. Biologically no evidence of disease (bNED) was defined at PSA levels < 2 microg/l. In order to compare the results of this treatment with other treatment modalities, the patient's pre-treatment data were used to calculate the estimated 5-year PSA relapse free survival using Kattan's nomograms for radical prostatectomy (RP) and 3D EBRT. After 6 years of follow-up, 129 patients remain alive. The actual 5-year relapse-free survival is 84%. None of the patients demonstrated clinical signs of local recurrence. The median PSA at follow-up among the relapse-free patients was 0.05 microg/l. Among the 80 patients who presented with clinical stage T3 tumours, 55 (68%) were relapse-free. The expected 5-year relapse-free survival using nomograms for RP and 3D EBRT was 54% and 70%, respectively. Late rectal toxicity RTOG grade 3 occurred in 1% of the patients. Late urinary tract toxicity RTOG grade 3 developed in 4% of the patients. Combined treatment, utilizing HDR, 3D EBRT and TAB, produces good clinical results. Rectal toxicity is acceptable. Urinary tract toxicity, most likely can be explained by the fact that during the first years of this treatment, no effort was made to localize the urethra, which was assumed to be in the middle of the prostate.


Cyclooxygenase-2 and 5-lipoxygenase pathways in diosgenin-induced apoptosis in HT-29 and HCT-116 colon cancer cells.
We studied the relationship between diosgenin-induced apoptosis and arachidonic acid metabolism in two cancer cell lines, the HT-29 and HCT-116. Diosgenin is a steroidal saponin known for its antiproliferative and pro-apoptotic effects on cancer cells. We focused our attention on two enzymes intervening in two different pathways of arachidonic metabolism: cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). HT-29 and HCT-116 cells express 5-LOX but only HT-29 cells express COX-2 since HCT-116 are deficient. After 40 microM diosgenin treatment, we observed apoptosis hallmarks in both cell lines but HT-29 cells were more resistant with delayed apoptosis. In these cells, COX-2 expression and activity were increased and for the first time we showed that diosgenin also increased 5-LOX expression and enhanced leukotriene B4 production. Inhibition of 5-LOX by AA-861 significantly reduced apoptosis in both cell lines but COX-2 inhibition by NS-398 strongly sensitized HT-29 cells to diosgenin-induced apoptosis compared to HCT-116 cells. In this study, we showed the implication of COX-2 and 5-LOX in diosgenin-induced apoptosis but these results demonstrate how difficult it is to assess the correlation between the apoptotic signalling pathway of diosgenin and arachidonic acid metabolism with certitude.


Effectiveness of Vision Therapy in School Children with Symptomatic Convergence Insufficiency.
To determine the effectiveness of vision therapy among Korean elementary school children with convergence insufficiency. A total of 235 elementary schoolchildren, 10.13 ± 2.45 years of age, were subjected to thorough eye examination including binocular vision testing. Of them, 32 individuals with symptomatic convergence insufficiency without strabismus, amblyopia, and ocular disease were chosen to receive vision therapy via brock string, barrel card, mirror stereoscope, prism goggles, and aperture rule for a duration of 8 weeks. The results showed that most of the participants had severe problems in near point of convergence. After the vision therapy, the average near point of convergence improved by approximately 5.48 ± 0.96 cm in all participants. Moreover, vision therapy had an effect on increasing near positive fusional vergence and decreasing exophoria. Negative relative accommodation improved to 2.54 ± 0.51 and positive relative accommodation improved to -3.10 ± 1.08 diopters. After treatment, near phoria was 4.19 ± 1.66 and distance phoria was 1.61 ± 0.71 prism diopters. Among convergence insufficiency symptoms, the following improved in particular: near point of convergence, exophoria, and near positive fusional vergence. These findings suggest that vision therapy is very effective to recover from symptomatic convergence insufficiency.


Acute tubular necrosis associated with propylene glycol from concomitant administration of intravenous lorazepam and trimethoprim-sulfamethoxazole.
A 46-year-old morbidly obese man was admitted to the medical intensive care unit with respiratory failure. He required pressure-control ventilation and high levels of sedation with continuous-infusion lorazepam. He developed Stenotrophomonas maltophilia pneumonia; treatment included scheduled intravenous trimethoprim-sulfamethoxazole. Each of these drugs contain several hundred milligrams/milliliter of propylene glycol. On day 17 of his hospital course, 3 days after starting the trimethoprim-sulfamethoxazole, the patient developed acute renal failure consistent with acute tubular necrosis. Propylene glycol toxicity was suspected; therefore, all drugs containing propylene glycol were discontinued, and laboratory data were collected. A marked osmol gap, metabolic acidosis, and renal toxicity were attributed to both continuous and large intermittent doses of intravenous propylene glycol. Particular attention should be paid to the total amount of propylene glycol provided to patients from administered drugs. Patients in the intensive care setting who require high doses of intravenous lorazepam for sedation, as well as antimicrobial therapy with trimethoprim-sulfamethoxazole for treatment of either Stenotrophomonas maltophilia or Pneumocystis carinii pneumonia, may be at increased risk for propylene glycol toxicity and should be monitored closely.


Large Head in Asymptomatic Child: A Subtle Presentation of Connective Tissue Disorder With Spontaneous Significant Intracerebral Bleed.
Three years old boy with reassuring development had presented to the Pediatric Neurology clinic with a referral due to a large head. Occipito-frontal circumference was more than 97th centile with an unremarkable neurological examination. MRI brain exhibited an acute on chronic large right frontoparietal subdural hematoma with prominent mass effect. Consequentially, the hematoma was evacuated by the neurosurgeon. Postoperative recovery stayed satisfactory. Hematology workup showed normal coagulation and clotting factors levels. Whole exome sequencing (WES) study revealed heterozygous variant c.5187G>A p.(Trp1729*) in gene FBN1 - pathogenic for Marfan syndrome. However, this variant has not yet been reported in association with cerebral arteritis/intracerebral bleed. On follow-up, the child remained asymptomatic clinically with static head size. This drags us towards the fact that significant yet asymptomatic spontaneous intracerebral hemorrhage can be an infrequent presentation in pediatrics in regard to connective tissue disorders. Moreover, children with Marfan syndrome having variant c.5187G>A p.(Trp1729*) of gene FBN1 can have a rare presentation with cerebral arteritis or intracerebral bleed.


Prevalence of antidepressants and biosimilars in elite sport.
The use of prescribed antidepressants by athletes has not been restricted in human sports since 2003, after the antidepressants bupropion and amineptine were removed from the list of prohibited substances. Recent awareness of antidepressants has been stimulated by reports from the media concerning possible misuse of antidepressants among healthy athletes. The prevalence of antidepressants has been monitored over the past ten years with screening procedures routinely used by WADA-accredited laboratories. The growth in antidepressant use among athletes peaked in 2007 and 2008 after a modest increase over the first eight years of this survey. Pharmacy prescriptions for antidepressants in Germany did not show a correlated growth during this period. The increasing variety of antidepressant medications has led to a continued increase in the diversity of antidepressant substances used by athletes and the 'normal' population. The number of different sports affected by the presence of antidepressants has increased in the past decade, especially in endurance sports. The predominance of female antidepressant users in the normal population was reflected in the athletes' group. We concluded from our results that the development of antidepressant prevalence in elite sports did not correlate with that among the general public in Germany.


Pathology of endometriosis.
In summary, endometriosis is a protean pathologic entity of uncertain nature and etiology, occurring commonly in the pelvis and rarely in remote sites. The lesions are characterized by gross and microscopic evidence of endometrium, past and present hemorrhage, inflammatory response, scarring, and dense adhesions. Electron microscopic evaluation suggests that early lesions are more common than appreciated, often retroperitoneal, and not clinically recognized. The diagnosis is established by the identification of microscopic foci of endometrium, although often the end stage reveals only hemosiderin-laden macrophages, foreign body giant cells, and proliferation of fibrous connective tissue. The presence of endometriosis alters the biology of the pelvic peritoneum in ways not universally agreed upon, but which undoubtedly influence the clinical manifestation of the disease.


Arsenic contents in rats' fur as an indicator of exposure to arsenic. Preliminary studies.
Since arsenic compounds have an affinity to thiol groups their greatest amounts can then be found in the tissues containing sulphur-rich proteins, like beta-keratin in skin, hair and nails. Accumulation of arsenic also depends on the macronutrient content in daily food ration. The deficiency and excess of both the protein and fat may contribute to a higher content of arsenic in the organism, including hair in human or fur in animals. Hair and fur is a good indicator of population exposure to many toxic substances, including arsenic. The degree of arsenic accumulation may depend on the diet and nutritional status. The aim of this study was to determine the effect of protein and fat in diet on the accumulation of arsenic in rats' fur. A total number of 70 male Buffalo rats (body weight 200 - 220 g, age - 6 weeks) were divided into 10 groups. Rats were housed in plastic cages (4 per cage) in a 12h light/dark cycle for 6 weeks. The diets of different protein and fat contents ware administered to the animals. Five of ten groups of rats received throughout the whole period 10 ppm sodium arsenite dissolved in distilled drinking water (about 250 µg As/animal/day). The arsenic were determined with the method of atomic adsorption spectrometry in conjunction with a graphite-furnace atomize using a Varian AA240FS apparatus. The highest arsenic concentrations were found in fur of rats which were given low protein diet and water with arsenic. The lowest arsenic contents were found in fur of rats, which were given control diet and high protein diet with arsenic in water. Balanced control diet or high protein diet protected organism from arsenic accumulation, only small increase of arsenic content in rats' fur, compared to the control group, was observed. arsenic, rats' fur, protein and fat in diet, exposure to arsenic.


Influence of professional vs. personal role on pain assessment and use of opioids.
Previous surveys have revealed that patient characteristics such as behavior may influence nurses decisions about pain assessment and analgesic use. This survey suggested that the role assumed by the nurse, professional versus personal, also influences these decisions. The findings further suggested that continuing education aimed at improving pain management needs to include not only knowledge about pain assessment and safety in the use of opioid analgesics, but also teaching methods that increase empathy.


Why treat? Better prevent: adult immunization.
Immunization is a safe, effective and simple way to prevent life threatening illnesses not only in children but also in adults. Vaccines are some of the safest medicines available which can relieve suffering costs related to these preventable diseases. The reason for underutilization of vaccines in adults are 1) Low prioritization of the importance of vaccines preventable diseases among adults 2) Uncertainty or lack of knowledge about the safety and efficacy 3) Lack of universal recommendations for all adults and 4) Financial constraints, especially in developing countries. Adult immunizations are administered in primary series like previously immunized, booster doses and periodic doses. Agents include Toxoids (Diphtheria and Tetanus), Live Virus Vaccines (Measles, Mumps and Rubella), and inactivated virus vaccines (Influenza), Inactive viral particles (Hepatitis B), inactivated bacterial polysaccharide vaccine (Pneumococcal) and Conjugate / Polysaccharide vaccine (Meningococcal). And also vaccines like Hepatitis A, Polio and Varicella may be recommended in some. Since the economy and literacy rate has shown a steady rise in the South Asia and people are being aware of different health problems through the recently advanced global communication, the education and awareness for immunization not only in children but also in adults need a special consideration. Keeping in view the statistical data of suffering costs related to the non-utilization of immunization in adults, the need of hour has come for utilization of immunization to emphasize its importance.


Amblyseius swirskii: what made this predatory mite such a successful biocontrol agent?
The predatory mite Amblyseius swirskii quickly became one of the most successful biocontrol agents in protected cultivation after its introduction into the market in 2005 and is now released in more than 50 countries. There are several key factors contributing to this success: (1) it can control several major pests including the western flower thrips, Frankliniella occidentalis, the whiteflies Bemisia tabaci and Trialeurodes vaporariorum and the broad mite, Polyphagotarsonemus latus, simultaneously in vegetables and ornamental crops; (2) it can develop and reproduce feeding on non-prey food sources such as pollen, which allows populations of the predator to build up on plants before the pests are present and to persist in the crop during periods when prey is scarce or absent; and (3) it can be easily reared on factitious prey, which allows economic mass production. However, despite the fact that A. swirskii provides growers with a robust control method, external demands were initially a key factor in promoting the use of this predator, particularly in Spain. In 2006, when exports of fresh vegetables from Spain were stopped due to the presence of pesticide residues, growers were forced to look for alternatives to chemical control. This resulted in the massive adoption of biological control-based integrated pest management programmes based on the use of A. swirskii in sweet pepper. Biological control increased from 5 % in 2005, 1 year before A. swirskii was commercially released, to almost 100 % of a total 6,000 ha of protected sweet pepper in Spain within 3 years. Later, it was demonstrated that A. swirskii was equally effective in other crops and countries, resulting in extensive worldwide use of A. swirskii in greenhouses.


Lumbar Sympathetic Block with Botulinum Toxin Type B for Complex Regional Pain Syndrome: A Case Study.
Lumbar sympathetic block (LSB) is an effective method for relief of sympathetically mediated pain in the lower extremities. To prolong the sympathetic blockade, sympathetic destruction with alcohol or radiofrequency has been used. The pre-ganglionic sympathetic nerves are cholinergic, and botulinum toxin (BTX) has been found to inhibit the release of acetylcholine at the cholinergic nerve terminals. Moreover, BTX type B (BTX-B) is more convenient to use than BTX type A. Based on these findings, we performed LSB on the 2 patients with complex regional pain syndrome (CRPS) in the lower extremity. Levobupivacaine 0.25% 5 mL mixed with BTX-B 5,000 IU was given under fluoroscopic guidance. Two months after LSB with BTX-B, pain intensity and the Leeds assessment of neuropathic symptoms and signs (LANSS) score were significantly reduced. Allodynia and coldness disappeared and skin color came back to normal. In conclusion, BTX-B can produce an efficacious and durable sympathetic blocking effect on patients with CRPS.


Organization of the human trichromatic cone mosaic.
Using high-resolution adaptive-optics imaging combined with retinal densitometry, we characterized the arrangement of short- (S), middle- (M), and long- (L) wavelength-sensitive cones in eight human foveal mosaics. As suggested by previous studies, we found males with normal color vision that varied in the ratio of L to M cones (from 1.1:1 to 16.5:1). We also found a protan carrier with an even more extreme L:M ratio (0.37:1). All subjects had nearly identical S-cone densities, indicating independence of the developmental mechanism that governs the relative numerosity of L/M and S cones. L:M cone ratio estimates were correlated highly with those obtained in the same eyes using the flicker photometric electroretinogram (ERG), although the comparison indicates that the signal from each M cone makes a larger contribution to the ERG than each L cone. Although all subjects had highly disordered arrangements of L and M cones, three subjects showed evidence for departures from a strictly random rule for assigning the L and M cone photopigments. In two retinas, these departures corresponded to local clumping of cones of like type. In a third retina, the L:M cone ratio differed significantly at two retinal locations on opposite sides of the fovea. These results suggest that the assignment of L and M pigment, although highly irregular, is not a completely random process. Surprisingly, in the protan carrier, in which X-chromosome inactivation would favor L- or M-cone clumping, there was no evidence of clumping, perhaps as a result of cone migration during foveal development.


Are in-dwelling catheters necessary for 24 hours after hysterectomy?
In-dwelling catheters for 24 hours after operation are used routinely in gynecologic surgery. This study assesses whether the immediate removal of an in-dwelling catheter after the operation affects the rate of recatheterization, febrile morbidity, symptomatic urinary tract infections, or subjective pain assessments. This study was a prospective randomized controlled trial comprised of 250 women who underwent hysterectomy and who did not require bladder suspension or strict fluid treatment. The in-dwelling catheter was removed either immediately after the operation or on the first day after the operation. The association between clinical variables and the length of catheterization were assessed by chi-squared analysis. Patients were assigned randomly into 2 groups, with no significant differences in the outcomes, only in the perception of pain. Clinical events included fever (>/=38.5 degrees C) that occurred in 6 patients in the in-dwelling catheter group compared with 5 patients in the early removal group (P=.01), symptomatic urinary tract infections in 3 patients in both groups (P=.99), and recatheterization in 3 patients in the in-dwelling catheter group compared with 5 patients in the early removal group (P=.17). Subjectively, patients in the early removal group reported significantly less pain than did the in-dwelling group (P<.001). The early removal of in-dwelling catheters after operation was not associated with an increased rate of febrile events, urinary tract infections, or need for recatheterization. In addition, subjective pain assessment was significantly less in the early removal group. Early removal of an in-dwelling catheter immediately after operation is not associated with adverse events.


Effects of platelet rich plasma on fascial healing in rats with fecal peritonitis
To evaluate the effects of platelet rich plasma (PRP) on the healing of fascia wherein peritonitis has been created. Twenty eight Wistar Albino rats were divided into four groups. Only a primary fascial repair following laparotomy was performed on Group 1, a primary fascial repair performed and PRP treatment applied following laparotomy on Group 2, and a fecal peritonitis created following laparotomy and a primary fascial repair carried out on Group 3. A fecal peritonitis was created following laparotomy and primary fascial repair and PRP treatment on the fascia was carried out on Group 4. TNF-α was found to be significantly lower in the control group (Group 1). It was detected at the highest level in the group in which fecal peritonitis was created and PRP applied (Group 4). TGF-β was determined as being significantly higher only in Group 4. Histopathologically, the differences between the groups in terms of cell infiltration and collagen deposition were not found to be significant. When platelet rich plasma was given histologically and biochemicaly as wound healing parameters cellular infiltration, collagen accumulation, and tissue hydroxyiproline levels were not increased but neovascularization, fibroblast activation and TNF Alfa levels were increased and PRP accelerated wound healing.


Experiences in supporting the structured collection of cancer nanotechnology data using caNanoLab.
The cancer Nanotechnology Laboratory (caNanoLab) data portal is an online nanomaterial database that allows users to submit and retrieve information on well-characterized nanomaterials, including composition, in vitro and in vivo experimental characterizations, experimental protocols, and related publications. Initiated in 2006, caNanoLab serves as an established resource with an infrastructure supporting the structured collection of nanotechnology data to address the needs of the cancer biomedical and nanotechnology communities. The portal contains over 1,000 curated nanomaterial data records that are publicly accessible for review, comparison, and re-use, with the ultimate goal of accelerating the translation of nanotechnology-based cancer therapeutics, diagnostics, and imaging agents to the clinic. In this paper, we will discuss challenges associated with developing a nanomaterial database and recognized needs for nanotechnology data curation and sharing in the biomedical research community. We will also describe the latest version of caNanoLab, caNanoLab 2.0, which includes enhancements and new features to improve usability such as personalized views of data and enhanced search and navigation.


Feeding a corn oil/sucrose-enriched diet enhances steatohepatitis in sedentary rats.
The current study investigated the combined effects of feeding a high-fat/high-sucrose (HF/HS) diet to rodents rendered sedentary via hindlimb unloading (HU). For 3 wk before HU, male Wistar rats were fed chow or a diet in which 32% of calories were derived from corn oil fat and 48% of calories from sucrose. Feeding continued during an additional 3-wk period of HU. Subsequently, blood samples were collected for determination of circulating leukocyte counts, insulin levels, and portal vein endotoxin. Inflammation, necrosis, and steatosis were assessed in formalin-fixed liver sections. No biochemical or histological evidence of injury was observed in control rats fed chow or HF/HS. HU increased circulating neutrophils and resulted in hyperinsulinemia. Mild hepatic fat accumulation and minimal focal necroinflammation were observed in this group. Feeding HF/HS during HU exacerbated hyperinsulinemia, hepatic steatosis, Kupffer cell content, and cytokine expression. Significant portal endotoxemia was noted in HU rats but was not influenced by HF/HS diet. On the other hand, feeding HF/HS significantly enhanced lipid peroxidation end products in liver of HU rats by approximately threefold compared with chow-fed rats. In summary, these findings demonstrate that feeding a high-calorie diet potentiates steatosis and injury in sedentary HU rats. Mechanisms underlying enhanced injury most likely involved lipid peroxidation. Importantly, these findings suggest that dietary manipulation combined with physical inactivity can be used to model steatohepatitis.


Voltage Control of Magnetic Anisotropy through Ionic Gel Gating for Flexible Spintronics.
In spite of recent rapid development of flexible electronics, voltage-tunable spintronic structures and devices on flexible substrates have been rarely studied. Here, voltage control of magnetic anisotropy (VCMA) is demonstrated via ionic gel (IG) gating on flexible polyimide substrates with a circuit operating voltage of 1.8 V. A reversible, nonvolatile VCMA switching of 114 Oe is achieved in Pt/Fe/Pt multilayer, where the spatial magnetic anisotropy distribution is determined quantitatively by electron spin resonance technique. This IG gating process is repeatable as the substrates are under different bending conditions. The voltage modulation of magnetic anisotropy through IG gating with excellent flexibility proposes potential applications in low-power wearable spintronic devices.


[A benign form of rheumatoid arthritis, associated with low IgG, IgM and IgA and C3-proactivator concentrations in the serum].
In 31 case studies, 29 patients diagnosed with definite rheumatoid arthritis and 2 patients with probable rheumatoid arthritis were investigated. The duration of the disease averaged 8 years with 3 years being the minimum. These patients received either no basic therapy or had not been treated six months previous to the investigation. Patients with low levels of immunoglobulins were shown to have significantly better functional capacity (Steinbrocker) and significantly less synovitis, erosions and joint destructions despite longer duration of the disease than the control group with higher levels of immunoglobulins and C3-proactivator. All patients with this benign development of rheumatoid arthritis had an IgG-level below 1000 mg/100 ml (mean 767 mg/100 ml +/- 166) and low levels of IgA (mean 194 mg/100 ml +/- 73), IgM (mean 111 mg/100 ml +/- 53) and C3-proactivator (mean 23 mg/100 ml +/-6). 50% of these patients had positive rheumatoid factors.


ADHD and EEG-neurofeedback: a double-blind randomized placebo-controlled feasibility study.
Electroencephalography (EEG)-neurofeedback has been shown to offer therapeutic benefits to patients with attention-deficit/hyperactivity disorder (ADHD) in several, mostly uncontrolled studies. This pilot study is designed to test the feasibility and safety of using a double-blind placebo feedback-controlled design and to explore the initial efficacy of individualized EEG-neurofeedback training in children with ADHD. Fourteen children (8-15 years) with ADHD defined according to the DSM-IV-TR criteria were randomly allocated to 30 sessions of EEG-neurofeedback (n = 8) or placebo feedback (n = 6). Safety measures (adverse events and sleep problems), ADHD symptoms and global improvement were monitored. With respect to feasibility, all children completed the study and attended all study visits and training sessions. No significant adverse effects or sleep problems were reported. Regarding the expectancy, 75% of children and their parent(s) in the active neurofeedback group and 50% of children and their parent(s) in the placebo feedback group thought they received placebo feedback training. Analyses revealed significant improvements of ADHD symptoms over time, but changes were similar for both groups. This pilot study shows that it is feasible to conduct a rigorous placebo-controlled trial to investigate the efficacy of neurofeedback training in children with ADHD. However, a double-blind design may not be feasible since using automatic adjusted reward thresholds may not work as effective as manually adjusted reward thresholds. Additionally, implementation of active learning strategies may be an important factor for the efficacy of EEG-neurofeedback training. Based on the results of this pilot study, changes are made in the design of the ongoing study.


Hitchhiking in space: Ancestry in adapting, spatially extended populations.
Selective sweeps reduce neutral genetic diversity. In sexual populations, this "hitchhiking" effect is thought to be limited to the local genomic region of the sweeping allele. While this is true in panmictic populations, we find that in spatially extended populations the combined effects of many unlinked sweeps can affect patterns of ancestry (and therefore neutral genetic diversity) across the whole genome. Even low rates of sweeps can be enough to skew the spatial locations of ancestors such that neutral mutations that occur in an individual living outside a small region in the center of the range have virtually no chance of fixing in the population. The fact that nearly all ancestry rapidly traces back to a small spatial region also means that relatedness between individuals falls off very slowly as a function of the spatial distance between them.


[Impact of hypocaloric and hypo-nitrogen parenteral nutrition on clinical outcome in postoperative patients: a multi-center randomized controlled trial of 120 cases].
To evaluate the impact of hypocaloric and hypo-nitrogen parenteral nutrition (PN) on infective complication rate, postoperative hospital stay and treatment cost in postoperative period. 120 patients with gastrointestinal tumors with the Nutrition Risk Screening (NRS) score of 3 or 4 undergoing radical gastrectomy in 5 hospitals were randomly assigned into 2 equal groups: control group, receiving PN with 30 (28 - 32) kcal x kg(-1) x d(-1) and nitrogen 0.20 (0.19 - 0.21) g x kg(-1) x d(-1) in regular "3 liter bag", and study group receiving calorie of 18 (range 16 - 20) kcal x kg(-1) x d(-1) and nitrogen of 0.10 (0.09 - 0.11) g x kg(-1) x d(-1) with triple chamber bag. PN support was infused continuously for at least six postoperative days through peripheral vein or peripherally inserted central catheter. The differences between these two groups in blood glucose level, infectious complication, phlebitis, systemic inflammatory response syndrome (SIRS), and duration of hospital stay after operation, and treatment cost. All data were evaluated by both intention to treat (ITT) analysis and per protocol (PP) analysis. There were no significant differences in the clinical baseline and operative types between the two groups. ITT analysis showed that the occurrence of hyperglycemia in postoperative period in the control group was 43.3%, significantly much higher than that in the study group (6.6%, P = 0.000). The infectious complication rate of the study group was 3.3%, significantly lower than that of the control group (16.6%, P = 0.0149), the phlebitis rate of the study group was 0.0%, significantly lower than that of the control group (18.3%, P = 0.0005). The SIRS rate of the study group was 25.0%, significantly lower than that of the control group (45.0%, P = 0.0216). PP analysis showed that the postoperative duration of hospital stay of the control group was 14.1 days +/- 5.8 days, significantly longer than that of the study group (12.4 days +/- 4.0 days, P = 0.047), the total PN cost of the study group was 3411.6 +/- 181.1 Yuan RMB, significantly higher than that of the control group (2945 +/- 162 Yuan RMB, P = 0.000); but the total post-operative cost of treatment of the control group was 13156 +/- 3282 Yuan RMB, significantly higher than that of the study group (11 642 +/- 3019 Yuan RMB, P = 0.010); and the time for compounding of the study group was 5.0 min +/- 1.7 min, significantly shorter than that of the control group (15.4 min +/- 3.7 min, P = 0.000). Hypocaloric and hypo-nitrogen PN in postoperative days 1 - 6 in patients with scores 3 or 4 decreases the rates of hyperglycemia, infectious complications, phlebitis, and SIRS, shortens the postoperative hospital stay, and lowers the cost of treatment comparing with conventional PN. The use of triple chamber bag shortens the compounding time of PN.


Effects of isradipine on endothelin-induced constriction of myometrial arteries in normotensive pregnant women.
The results of our previous studies suggested that endothelin-1 (ET-1) might be contributory to the impaired uteroplacental blood flow seen in preeclampsia. The aim of this study was to investigate the in vitro influence of isradipine on ET-1-induced contraction of myometrial resistance arteries from pregnant women, as these vessels are partly responsible for the regulation of uteroplacental blood flow in preeclampsia. Small myometrial arteries were dissected from myometrium obtained from 20 normotensive term pregnant women undergoing elective cesarean section and mounted in a tissue chamber. Tension was recorded isometrically. When ET-1 (10(-8) mol/L)-contracted vessels were exposed to increasing concentrations (10(-6), 10(-5), and 10(-4) mol/L) of isradipine, the myometrial arteries demonstrated essentially no relaxation. A significant mean relaxation of 31% was seen only with the highest isradipine concentration of 10(-3) mol/L. Pretreatment with isradipine attenuated ET-1-induced contraction by 26% at 3 x 10(-4) mol/L and by up to 80% at 10(-3) mol/L. Preincubation with lower concentrations of isradipine did not significantly reduce subsequent ET-1 contraction. The present study has thus shown that isradipine at high concentrations counteracts ET-1-induced constriction of myometrial arteries in term pregnant women. Pretreatment with isradipine at high concentrations attenuates the ET-1 contraction.


Sending, receiving, and nonconsensually sharing nude or near-nude images by youth.
There is growing evidence about the prevalence of sending, receiving, or resharing nude images by youth (sexting). Less is known about the demographic, technology use, and social context correlates of sexting. Using logistic regression, we looked at predictors of sexting behaviors in minors. Participants were a market panel sample of 394 youths aged 9-12 and 602 youths aged 13-17 (Mage = 13.5, SD = 2.50, 60.3% females) recruited for an anonymous online survey in the United States. The survey comprised questions about demographic characteristics, sexting behaviors, technology use, attitudes, and perceived norms. The four outcomes were sending nude or near-nude images or videos (images), receiving images sent without the depicted person's knowledge, nonconsensually resharing images, or having one's own images nonconsensually reshared. Regression analyses showed gender, gender/sexual minority status, use of dating apps and particular online platforms, self-sharing and resharing attitudes, and friend norms predicted sending images. Age, resharing attitudes, and friend norms all predicted receiving nude images of other youths. Household income, geographic location, some online platforms, resharing attitudes, and friend norms all predicted nonconsensual resharing of nudes. Age, use of encrypted apps, and friend norms predicted having one's own image nonconsensually reshared. We partially replicated prior research by finding associations between age and gender. Further, we identified technology use factors including the use of dating apps and particular platforms. Attitudes about sexting and perceived friend norms were robust across sexting behaviors, suggesting these factors are potentially important for intervention.


Telomerase in brain tumors.
In recent years, many scientists involved in cancer research have directed their attention to telomerase, an enzymatic complex which is specifically involved in duplicating telomeres, the very ends of linear chromosomes. The discovery that most immortal cell lines in vitro and human tumor cells in vivo have telomerase activity, in contrast to telomerase-negative normal somatic cells, has made telomerase a candidate for use as a molecular marker of malignancy and even as a target for anticancer therapies. Thus, the assessment of the role of telomerase activity in neoplastic transformation has become a key issue in oncology, as stated by the exponential increase of papers on telomerase in the last 5 years. In this paper, we review some recent data from the literature, including our own studies, on the regulation of telomerase activity in brain tumors.


TCRklass: a new K-string-based algorithm for human and mouse TCR repertoire characterization.
The next-generation sequencing technology has promoted the study on human TCR repertoire, which is essential for the adaptive immunity. To decipher the complexity of TCR repertoire, we developed an integrated pipeline, TCRklass, using K-string-based algorithm that has significantly improved the accuracy and performance over existing tools. We tested TCRklass using manually curated short read datasets in comparison with in silico datasets; it showed higher precision and recall rates on CDR3 identification. We applied TCRklass on large datasets of two human and three mouse TCR repertoires; it demonstrated higher reliability on CDR3 identification and much less biased V/J profiling, which are the two components contributing the diversity of the repertoire. Because of the sequencing cost, short paired-end reads generated by next-generation sequencing technology are and will remain the main source of data, and we believe that the TCRklass is a useful and reliable toolkit for TCR repertoire analysis.


[Esophagogastric bypass anastomosis for benign stricture of cardia].
The aim of the study is to discuss our observations concerning oesophagogastric bypass anastomosis in cases with scar stricture of cardia in long-term achalasia (megaoesophagus). The Heller operation is ineffective in such patients and the resection of cardia with oesophagogastric anastomosis is a large and controversial operation. 16 patients were operated (6 of them after ineffective cardiomyotomy). In all cases long-term dysphagia, big loss of weight and large, S-shaped oesophagus lying on the diaphragm were found. The left side thoracotomy was performed and fundus of the stomach was dislocated to the chest through dilatatored oesophageal hiatus and with the oesophagus above the cardia. There were no postoperative complications. However, dysphagia regressed. The remote results (from 1 year to 7 years) in 11 patients were analysed. The general condition was satisfactory. No dysphagia and gastrooesophageal reflux was revealed. Anastomosis was efficient in X-ray examination. Our observations indicate that oesophagogastric anastomosis is a procedure of choice in the treatment of long-term achalasia with stricture of cardia and megaoesophagus.


Special Care Dentistry: Part 2. dental management of patients with drug-related acquired bleeding disorders.
The first of this series of three articles discussed the dental management of patients with inherited bleeding disorders. This paper will discuss and outline the dental management of patients with acquired bleeding disorders that can result from drug therapy. These may be associated with vascular defects, platelet defects or coagulation defects. In an age when people are living longer, and medical interventions are continually becoming more advanced, clinicians will need to be aware of systemic disorders and treatments that may cause complications in the dental setting. According to National Statistics, the UK population is projected to increase by 0.7% by 2016. This trend is shared with other European countries which also have ageing populations. The proportion of people aged over 65 is predicted to increase from 16% in 2006 to 22% in 2031. Being able to recognize which drugs may cause bleeding problems at an early stage will lead to good patient management, particularly in planning and delivering treatment following invasive procedures such as dental extractions. Whilst most patients can be successfully treated in general dental practice, the clinician may need to make a decision on whether or not to refer a patient to specialist services for all dental treatment, or to share care between primary care and specialist services for selected procedures.


Sintering behaviour of hydroxyapatite bioceramics.
The sintering behaviour of a commercial HA and synthesized HA was investigated over the temperature range of 700 degrees C to 1400 degrees C in terms of phase stability, bulk density, Young's modulus and Vickers hardness. In the present research, a wet chemical precipitation reaction was successfully employed to synthesize a submicron, highly crystalline, high purity and single phase stoichiometric HA powder that is highly sinteractive particularly at low temperature regimes below 1100 degrees C. It has been revealed that the sinterability of the synthesized HA was significantly greater than that of the commercial HA. The temperature for the onset of sintering and the temperature required to achieve densities above 98% of theoretical value were approximately 150 degrees C lower for the synthesized HA than the equivalent commercial HA. Nevertheless, decomposition of HA phase upon sintering was not observed in the present work for both powders.


Whole genome re-sequencing of sweet cherry (Prunus avium L.) yields insights into genomic diversity of a fruit species.
Sweet cherries, Prunus avium L. (Rosaceae), are gaining importance due to their perenniallity and nutritional attributes beneficial for human health. Interestingly, sweet cherry cultivars exhibit a wide range of phenotypic diversity in important agronomic traits, such as flowering time and defense reactions against pathogens. In this study, whole-genome resequencing (WGRS) was employed to characterize genetic variation, population structure and allelic variants in a panel of 20 sweet cherry and one wild cherry genotypes, embodying the majority of cultivated Greek germplasm and a representative of a local wild cherry elite phenotype. The 21 genotypes were sequenced in an average depth of coverage of 33.91×. and effective mapping depth, to the genomic reference sequence of 'Satonishiki' cultivar, between 22.21× to 36.62×. Discriminant analysis of principal components (DAPC) with SNPs revealed two clusters of genotypes. There was a rapid linkage disequilibrium decay, as the majority of SNP pairs with r2 in near complete disequilibrium (>0.8) were found at physical distances less than 10 kb. Functional analysis of the variants showed that the genomic ratio of non-synonymous/synonymous (dN/dS) changes was 1.78. The higher dN frequency in the Greek cohort of sweet cherry could be the result of artificial selection pressure imposed by breeding, in combination with the vegetative propagation of domesticated cultivars through grafting. The majority of SNPs with high impact (e.g., stop codon gaining, frameshift), were identified in genes involved in flowering time, dormancy and defense reactions against pathogens, providing promising resources for future breeding programs. Our study has established the foundation for further large scale characterization of sweet cherry germplasm, enabling breeders to incorporate diverse germplasm and allelic variants to fine tune flowering and maturity time and disease resistance in sweet cherry cultivars.


Associations between prepregnancy body mass index, gestational weight gain, and pregnancy outcomes in women with twin pregnancies: A five-year prospective study.
The purpose of this project was to investigate the relationship between prepregnancy body mass index (ppBMI), gestational weight gain (GWG), and pregnancy outcomes in women with twin pregnancies. A prospective cohort of 369 women with dichorionic diamniotic twin pregnancies was recruited from 2016 to 2020. According to ppBMI using Chinese BMI classifications, they were categorized into the underweight (BMI < 18.5 kg/m2 ), normal (BMI 18.5-23.9 kg/m2 ), and overweight and obese (BMI ≥ 24 kg/m2 ) groups. In each ppBMI group, they were divided into two subgroups based on the presence or absence of the complications such as gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and small for gestational age (SGA). The outcomes including GDM, HDP, and SGA were compared among three ppBMI groups, and the associations of GWG with these outcomes within each ppBMI category were analyzed. Twin-pregnant women with overweight and obesity were at increased risks of HDP (aOR = 4.417 [95% CI = 1.826-9.415]) and SGA (2.288 [1.102-4.751]), whereas underweight women were prone to deliver SGA newborns (2.466 [1.157-5.254]). Women with GDM gained less weight during pregnancy than those without GDM within each ppBMI category. For overweight and obese women, greater GWG increased the incidence of HDP (1.235 [1.016-1.500]) and decreased the risk of SGA (0.818 [0.702-0.953]). Both ppBMI and GWG in twin-pregnant women were strongly associated with HDP and SGA, but not GDM.


Clinician-Driven AI: Code-Free Self-Training on Public Data for Diabetic Retinopathy Referral.
Democratizing artificial intelligence (AI) enables model development by clinicians with a lack of coding expertise, powerful computing resources, and large, well-labeled data sets. To determine whether resource-constrained clinicians can use self-training via automated machine learning (ML) and public data sets to design high-performing diabetic retinopathy classification models. This diagnostic quality improvement study was conducted from January 1, 2021, to December 31, 2021. A self-training method without coding was used on 2 public data sets with retinal images from patients in France (Messidor-2 [n = 1748]) and the UK and US (EyePACS [n = 58 689]) and externally validated on 1 data set with retinal images from patients of a private Egyptian medical retina clinic (Egypt [n = 210]). An AI model was trained to classify referable diabetic retinopathy as an exemplar use case. Messidor-2 images were assigned adjudicated labels available on Kaggle; 4 images were deemed ungradable and excluded, leaving 1744 images. A total of 300 images randomly selected from the EyePACS data set were independently relabeled by 3 blinded retina specialists using the International Classification of Diabetic Retinopathy protocol for diabetic retinopathy grade and diabetic macular edema presence; 19 images were deemed ungradable, leaving 281 images. Data analysis was performed from February 1 to February 28, 2021. Using public data sets, a teacher model was trained with labeled images using supervised learning. Next, the resulting predictions, termed pseudolabels, were used on an unlabeled public data set. Finally, a student model was trained with the existing labeled images and the additional pseudolabeled images. The analyzed metrics for the models included the area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, and F1 score. The Fisher exact test was performed, and 2-tailed P values were calculated for failure case analysis. For the internal validation data sets, AUROC values for performance ranged from 0.886 to 0.939 for the teacher model and from 0.916 to 0.951 for the student model. For external validation of automated ML model performance, AUROC values and accuracy were 0.964 and 93.3% for the teacher model, 0.950 and 96.7% for the student model, and 0.890 and 94.3% for the manually coded bespoke model, respectively. These findings suggest that self-training using automated ML is an effective method to increase both model performance and generalizability while decreasing the need for costly expert labeling. This approach advances the democratization of AI by enabling clinicians without coding expertise or access to large, well-labeled private data sets to develop their own AI models.


Myxomatous Mitral Valve with Prolapse and Flail Scallop.
Myxomatous mitral valve with prolapse are classically seen with abnormal leaflet apposition during contraction of the heart. Hemodynamic disorders can result from eccentric mitral regurgitation usually caused by chordae tendinae rupture or papillary muscle dysfunction. Echocardiography is the gold standard for evaluation of leaflet flail and prolapse due to high sensitivity and specificity. Though most mitral valve prolapse are asymptomatic those that cause severe regurgitation need emergent surgical intervention to prevent disease progression. We report a 54 year old Hispanic male who presented with progressively worsening dyspnea and palpitations. Initial evaluation was significant for atrial fibrillation on electrocardiogram with subsequent echocardiography revealing myxomatous mitral valve with prolapse. Following surgical repair of the mitral valve, the dyspnea and palpitations resolved. Mitral valve prolapse is a common valvular abnormality but the pathogenic cause of myxomatous valves has not been elucidated. Several theories describe multiple superfamilies of proteins to be involved in the process. Proper identification of these severe mitral regurgitation due to these disease valves will help relieve symptomatic mitral valve prolapse patients.


Relating anatomy to function in Alzheimer's disease: neuropsychological profiles predict regional neuropathology 5 years later.
Neuropsychological profiles were assessed in a large group of nondemented control subjects (n = 261) and individuals with dementia of the Alzheimer type (DAT) (n = 407) by subjecting their psychometric test results to a factor analysis. Nondemented control subjects were functionally homogeneous with only one factor accounting for the results. The results of the factor analysis on the very mild DAT and mild DAT groups, however, yielded a mental control/frontal factor, a memory-verbal/temporal factor, and a visuospatial/parietal factor. Forty-one of the original set of participants came to autopsy an average of 5.1 years after psychometric testing and had neurofibrillary tangles, total senile plaques, and cored senile plaques estimated from frontal, temporal, and parietal regions. The results of correlations indicated that the relative burden of cored senile plaques was systematically related to the three psychometric factors. These results suggest a connection between the specific functions as defined by neuropsychological measures and specific neuropathology occurring in associated areas of cortex.


Diurnal differences in glycemic responses, insulin responses and cognition after rice-based meals.
The variation in glycemic responses to white rice caused by the circadian rhythm has been widely investigated but remain controversial. This study investigated diurnal differences in the effect of rice meals on glycemic responses, insulin responses, satiety, and acute cognitive function. A total of 20 healthy participants in Group 1 and 14 in Group 2 were served identical servings of cooked white rice containing 50 g of available carbohydrates at 8:00 a.m. (rice at breakfast), 12:30 p.m. (rice at lunch), and 5:00 p.m. (rice at early supper) in a randomized order. Postprandial blood glucose, insulin, satiety, and cognitive performance tests were conducted for each test meal. The rice at an early supper elicited significantly milder glycemic responses than did the rice at lunch and resulted in a lower insulin sensitivity than did rice at breakfast. No difference was observed among the test meals in terms of hunger and prospective food intake. Diurnal acute cognitive performance did not differ considerably among the meals. A correlation analysis indicated that low variability in glycemic responses was positively associated with superior cognitive performance. A high-glycemic index white rice supper at 5:00 p.m. may facilitate daily glycemic management.


Phylogenomic analyses of 539 highly informative loci dates a fully resolved time tree for the major clades of living turtles (Testudines).
Accurate time-calibrated phylogenies are the centerpiece of many macroevolutionary studies, and the relationship between the size and scale of molecular data sets and the density and accuracy of fossil calibrations is a key element of time tree studies. Here, we develop a target capture array specifically for living turtles, compare its efficiency to an ultraconserved element (UCE) dataset, and present a time-calibrated molecular phylogeny based on 539 nuclear loci sequenced from 26 species representing the breadth of living turtle diversity plus outgroups. Our gene array, based on three fully sequenced turtle genomes, is 2.4 times more variable across turtles than a recently published UCE data set for an identical subset of 13 species, confirming that taxon-specific arrays return more informative data per sequencing effort than UCEs. We used our genomic data to estimate the ages of living turtle clades including a mid-late Triassic origin for crown turtles and a mid-Carboniferous split of turtles from their sister group, Archosauria. By specifically excluding several of the earliest potential crown turtle fossils and limiting the age of fossil calibration points to the unambiguous crown lineage Caribemys oxfordiensis from the Late Jurassic (Oxfordian, 163.5-157.3Ma) we corroborate a relatively ancient age for living turtles. We also provide novel age estimates for five of the ten testudine families containing more than a single species, as well as several intrafamilial clades. Most of the diversity of crown turtles appears to date to the Paleogene, well after the Cretaceous-Paleogene mass extinction 66mya.


Osteochondral autologous transfer combined with valgus high tibial osteotomy: long-term results and survivorship analysis.
Deep osteochondral defects of the medial femoral condyle in young and active patients are a serious condition that might lead to early osteoarthritis of the knee joint. Concomitant varus malalignment most likely promotes this process because of overloading of the medial compartment. Osteochondral autologous transfer (OAT) combined with valgus high tibial osteotomy (HTO) might therefore be a comprehensive solution to preserve long-term knee function in these patients. To evaluate clinical long-term results and analyze survival rates (conversion to knee joint arthroplasty) after combined OAT and valgus HTO in young and active patients with symptomatic osteochondral defects of the medial femoral condyle and concomitant varus malalignment. Case series; Level of evidence, 4. Between 1998 and 2008, combined OAT and valgus HTO was performed in 86 patients with deep osteochondral defects of the medial femoral condyle and concomitant varus malalignment >2°; 74 patients (86%) were available for follow-up evaluation. The mean age of patients was 38 years, and the mean follow-up time was 7.5 years. Knee function was assessed using the Lysholm score, and pain intensity was measured using the visual analog scale (VAS). The survival rates of this combined procedure were evaluated. Failure was defined as conversion to knee joint arthroplasty during the follow-up period. Adjusted to follow-up time, the Lysholm score showed a mean increase of 33 points (95% CI, 27.1-39.4; P < .001) from 40 to 73, representing a significant improvement compared with preoperatively. The VAS score decreased by a mean of 4.8 points (95% CI, 4.1-5.5; P < .001) from 7.5 to 2.7, and 93% of the patients were satisfied with the results of the operative procedure. Mean survival rates were 95.2% ± 2.7% at 5 years, 93.2% ± 3.3% at 7 years, and 90.1% ± 4.4% at 8.5 years after surgery. Combined OAT and valgus HTO is an option to successfully treat patients with deep osteochondral defects of the medial femoral condyle and concomitant varus malalignment. Significantly improved knee function, decreased pain intensity, and a high survivorship rate can be expected up to 8.5 years postoperatively.


A hybrid technique for treating multilevel cervical myelopathy: Cervical artificial disc replacement combined with fusion.
Clinical and radiographic outcomes of multilevel cervical myelopathy (MCM) patients treated with a hybrid technique combining cervical anterior corpectomy and fusion (ACF) with cervical artificial disc replacement (C-ADR) were evaluated. A total of 23 patients including 14 females and 9 males (mean age, 48.3 years) were treated with the hybrid technique and they were followed up for an average time of 35 months (range from 24 to 40 months). Arm- and neck-pain visual analogue scale (VAS) scores, neck disability index (NDI) scores and C2-7 range of motion (ROM) preoperation and 6 weeks, 3 and 24 months postoperation were assessed and compared. Fusion success and system failure based on anteroposterior (AP), lateral and flexion/extension X-rays were examined by an independent reviewer. Postoperative VAS, NDI and ROM were decreased significantly at all the time-points examined, as compared to preoperative scores (P<0.05). The results revealed that this hybrid technique is both technically feasible and effective for the treatment of MCM. However, future comparative studies will be required to determine the potential benefits and pitfalls of this hybrid technique.


YY1 Binding to Regulatory Elements That Lack Enhancer Activity Promotes Locus Folding and Gene Activation.
Enhancers activate their cognate promoters over huge distances but how enhancer/promoter interactions become established is not completely understood. There is strong evidence that cohesin-mediated loop extrusion is involved but this does not appear to be a universal mechanism. Here, we identify an element within the mouse immunoglobulin lambda (Igλ) light chain locus, HSCλ1, that has characteristics of active regulatory elements but lacks intrinsic enhancer or promoter activity. Remarkably, knock-out of the YY1 binding site from HSCλ1 reduces Igλ transcription significantly and disrupts enhancer/promoter interactions, even though these elements are >10 kb from HSCλ1. Genome-wide analyses of mouse embryonic stem cells identified 2671 similar YY1-bound, putative genome organizing elements that lie within CTCF/cohesin loop boundaries but that lack intrinsic enhancer activity. We suggest that such elements play a fundamental role in locus folding and in facilitating enhancer/promoter interactions.


Lipid rafts can form in the inner and outer membranes of Borrelia burgdorferi and have different properties and associated proteins.
Lipid rafts are microdomains present in the membrane of eukaryotic organisms and bacterial pathogens. They are characterized by having tightly packed lipids and a subset of specific proteins. Lipid rafts are associated with a variety of important biological processes including signaling and lateral sorting of proteins. To determine whether lipid rafts exist in the inner membrane of Borrelia burgdorferi, we separated the inner and outer membranes and analyzed the lipid constituents present in each membrane fraction. We found that both the inner and outer membranes have cholesterol and cholesterol glycolipids. Fluorescence anisotropy and FRET showed that lipids from both membranes can form rafts but have different abilities to do so. The analysis of the biochemically defined proteome of lipid rafts from the inner membrane revealed a diverse set of proteins, different from those associated with the outer membrane, with functions in protein trafficking, chemotaxis and signaling.


Effect of beta-sitosterol on ultrastructure of liver cells in young and aged mice.
The effects of beta-sitosterol on liver ultrastructure were studied using young and aged male mice. Both groups of mice were fed a beta-sitosterol or a control diet. The beta-sitosterol diet contained 1% beta-sitosterol. Ultrastructural differences in the liver cells were evident between two groups fed the two diets. The number of peroxisomes was significantly greater in the liver cells of both young and aged mice fed the beta-sitosterol diet than in those fed the control diet. There were also significant differences in the maximum length of lipid droplets between the young and aged mice fed the beta-sitosterol diet. These results suggest that beta-sitosterol affects liver ultrastructure, and that some ultrastructural differences in liver cells exist between young and aged mice fed the beta-sitosterol diets.


Endothelial control of vascular and myocardial function in heart failure.
The effect of vascular endothelium, endocardium, and coronary endothelium on vascular tone and myocardial contraction-relaxation sequence in heart failure is discussed. Vascular endothelium affects underlying vascular smooth muscle through paracrine secretion of relaxing and constricting factors. In heart failure, systemic vasoconstriction results not only from neuroendocrine activation, but also from disturbed local endothelial control of vascular tone because of impaired endothelial-dependent vasodilation and because of increased plasma concentration of endothelin. Experimental evidence obtained in isolated cardiac muscle strips established the influence of endocardial endothelium on the duration of myocardial contraction and on the onset of myocardial relaxation. By analogy to vascular endothelium, both diffusible agents that abbreviate (endothelial-derived relaxation factor-like substance) and those that prolong (endocardin) myocardial contraction have been shown to be released from the endocardium. Similar agents are released from the coronary endothelium and, because of the close proximity of capillaries and myocytes, could exert a major effect on myocardial performance. Endothelial dysfunction and concomitant lack of release of myocardial relaxant factors could explain left ventricular relaxation abnormalities observed in the cardiac allograft or in arterial hypertension. Since endothelial-derived relaxation factor or nitric oxide mediates the coronary reactive hyperemic response, a negative inotropic action of nitric oxide could contribute to left ventricular failure when left ventricular wall stress is elevated, as occurs after myocardial infarction in the noninfarcted zone and during left ventricular volume or pressure overload in the absence of adequate hypertrophy.


Effect of heme on globin messenger RNA synthesis in spleen erythroid cells.
Synthesis of globin mRNA in erythroid spleen cells from anemic mice was measured after in vitro incubation under conditions in which the level of intracellular heme was manipulated. This newly synthesized globin mRNA was isolated by hybridization with globin cDNA covalently bound to cellulose. Isonicotinic acid hydrazide (INH) and penicillamine were used as specific inhibitors of heme synthesis. It has been found that a 120-min incubation of spleen erythroid cells with 5mM INH or 5mM penicillamine reduced [3H] uridine incorporation into globin mRNA by 24% or 36%, respectively. The addition of heme to INH- or penicillamine-treated cells almost completely restored [3H] uridine incorporation into globin mRNA. These results indicate that heme stimulates transcription of processing of globin mRNA.


Influence of amifostine on toxicity of CHOP in elderly patients with aggressive non-Hodgkin's lymphoma--a phase II study.
Due to concerns about toxicity, many elderly patients with aggressive non-Hodgkin's lymphoma (NHL) are not considered candidates for standard chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). The cytoprotective agent amifostine has the potential to reduce toxicity when added to chemotherapy. The purpose of the current study was to examine the toxicity of CHOP combined with amifostine in elderly patients with aggressive NHL. A prospective phase II study was performed in patients aged 60 years and older. Patients with stage I/II disease received 4 cycles of CHOP followed by involved-field irradiation. Patients with stage III/IV received 6-8 cycles of CHOP. Amifostine (740 mg/m(2)) was administered as a 15-min i.v. infusion immediately before chemotherapy. Forty-one (median age 69.5 years, range 60-87) of 49 consecutive previously untreated patients, aged 60 years and older, with aggressive NHL seen in our center were included in the study. Twenty-one patients had stage I/II disease and 20 had stage III/IV disease. The patients received a total of 207 cycles of amifostine-CHOP. Infusion of amifostine caused mild to moderate transient side effects, including a drop of systolic blood pressure >20 mmHg in 54 cycles and nausea/vomiting in 36 cycles. Hematotoxicity of CHOP consisted of leukopenia grade 4 in only 15.4% of cycles. There were two cases of grade 3 anemia. No thrombocytopenia higher than grade 2 occurred. Febrile neutropenia was rare, occurring in 4.3% of cycles. One patient died after the first CHOP administration because of anthracycline-related acute cardiomyopathy (corresponding to a toxic death rate of 2.4%). The complete response rates were 85 and 75% in stage I/II and stage III/IV patients, respectively. After median follow-up of 33 months (range 17-50 months) the median overall survival was not reached in patients with stage I/II and was found to be 32 months in patients with stage III/IV. At 2 years, 76% of patients with stage I/II and 70% with stage III/IV were alive. Twelve of the 15 patients who died were aged older than 70. Amifostine pre-treatment was associated with a low toxicity of CHOP in elderly patients with aggressive NHL treated with curative intent. Treatment outcomes appeared not to be impaired by the addition of amifostine to CHOP. This schedule merits further testing in a randomized trial.


iHOPerator: user-scripting a personalized bioinformatics Web, starting with the iHOP website.
User-scripts are programs stored in Web browsers that can manipulate the content of websites prior to display in the browser. They provide a novel mechanism by which users can conveniently gain increased control over the content and the display of the information presented to them on the Web. As the Web is the primary medium by which scientists retrieve biological information, any improvements in the mechanisms that govern the utility or accessibility of this information may have profound effects. GreaseMonkey is a Mozilla Firefox extension that facilitates the development and deployment of user-scripts for the Firefox web-browser. We utilize this to enhance the content and the presentation of the iHOP (information Hyperlinked Over Proteins) website. The iHOPerator is a GreaseMonkey user-script that augments the gene-centred pages on iHOP by providing a compact, configurable visualization of the defining information for each gene and by enabling additional data, such as biochemical pathway diagrams, to be collected automatically from third party resources and displayed in the same browsing context. This open-source script provides an extension to the iHOP website, demonstrating how user-scripts can personalize and enhance the Web browsing experience in a relevant biological setting. The novel, user-driven controls over the content and the display of Web resources made possible by user-scripts, such as the iHOPerator, herald the beginning of a transition from a resource-centric to a user-centric Web experience. We believe that this transition is a necessary step in the development of Web technology that will eventually result in profound improvements in the way life scientists interact with information.


Paraneoplastic movement disorders.
Paraneoplastic movement disorders are rare, autoimmune-mediated, nonmetastatic complications of malignant neoplasms. Common paraneoplastic movement disorders include paraneoplastic chorea, dystonia, cerebellar degeneration, different types of encephalitis, opsoclonus-myoclonus syndrome, stiff person syndrome, and neuromyotonia. Syndromes usually develop before tumor diagnosis, have subacute onset, and are associated with serum or cerebrospinal fluid antibodies. Two types of antibodies can be distinguished: antibodies against nuclear and cytoplasmic neuronal antigens (anti-Hu, anti-Ri, anti-Yo, anti-Ma, anti-CV2/CRMP5, anti-Gephrin, and anti-GABATRAP) and antibodies recently identified against cell surface and synaptic proteins (anti-NMDAR, anti-LGI1, and anti-Caspr2). These two types differ from each other in a few important aspects. Antibodies against cell surface and synaptic protein disrupt cell-surface antigens. Clinical symptoms are related to the disruption of antigens and potentially can be reversed by immunotherapy. The association between these antibodies and malignancy is much less consistent. On the other hand, antibodies against nuclear and cytoplasmic neuronal antigens seem to be not pathogenic; however, they most likely indicate a T-cell-mediated immune response against neurons. Due to T-cell-mediated neuronal loss, response to immunotherapy is generally disappointing. Early recognition of all these diseases is crucial because it may lead to the disclosure of occult cancer. This review is focused on paraneoplastic movement disorders with emphasis on clinical presentations, investigational findings, and therapeutic results.


The patient perspective on a first raised PSA test.
Approximately 350 000 prostate-specific antigen (PSA) tests are undertaken in New Zealand on a quarter of a million men each year. A number of studies have looked at PSA testing done by general practitioners (GPs) and subsequent outcomes. Few have looked at the patient perspective after a raised PSA result. To explore patient experiences up to and following a raised PSA test. Thirty-one general practices within the Midland region were recruited. Community laboratory databases were used to identify all men with a first raised PSA test during 2010. Questionnaires were sent to these men. One hundred and ninety-four (63%) eligible responses were received from 307 eligible men delivered questionnaires. For 54% of men this was their first PSA test. Most men (66%) identified that their PSA test was initiated by their GP. Forty-three percent of men identified having symptoms at the time of their first raised PSA test. A digital rectal examination (DRE) was performed on 73% of men at the time of the test. Fifty-eight percent of men were referred to see a specialist. Maori men were less likely to be referred after a raised PSA. Of all men referred, 61% received a biopsy. PSA testing is predominantly initiated by GPs. We found the care pathway is variable for men after an elevated PSA result. Standardisation of the pathway prior to and post diagnosis would assist patients in knowing what to expect and would aid in GP management of men being investigated for prostate cancer.


Yeast opsonization and phagocytosis studied by a visual assay and measurement of neutrophil chemiluminescence.
Yeast opsonization was examined by a visual phagocytic assay which identified intracellular particles by means of staining with reduced nitroblue tetrazolium, and by measurement of the chemiluminescent response of neutrophils to opsonized particles. With both assays optimal opsonization was dependent on the classical complement pathway at lower serum concentrations, however, alternative pathway activity alone was able to opsonic optimally at higher serum concentrations. Examination of the complement pathway and opsonic activity of sera from 17 children with atopic dermatitis revealed 2 subjects with defective alternative pathway lytic activity. There was no significant difference in the opsonic activity between atopic children and control subjects. This investigation does not confirm the suggestion that yeast opsonization is a common defect in atopic individuals and indicates yeast can be opsonized by both classical and alternative pathways.


Imaging the hip joint in osteoarthritis: A place for ultrasound?
Osteoarthritis has traditionally been imaged with conventional radiographs; this has been regarded as the reference technique in osteoarthritis for a long time. However, in recent years, innovative imaging techniques such as ultrasonography have been used to obtain a better understanding of this disease. This is mainly due to tremendous technical advances and progressive developments of ultrasound equipment occurring over the past decade. Ultrasonography has been demonstrated to be a valuable imaging technique in the diagnosis and management of osteoarthritis of the hip joint. Application of this imaging methodology for osteoarthritis has improved the understanding of the disease process and may aid in the assessment of the efficacy of future therapies. The execution of ultrasound-guided procedures with safety and reliability has a relevant significance in patient management of osteoarthritis of the hip joint. This paper reviews the use of ultrasound as an imaging technique for the evaluation and treatment of osteoarthritis hip joint.


Etoposide (VP-16-213) in malignant brain tumors: a phase II study.
Twenty-two consecutive patients with recurrent malignant brain tumors after radiation therapy and systemic combination chemotherapy with BCNU and vincristine, four of whom were not evaluable due to early death, were treated with etoposide (VP-16-213) (50-100 mg/m2 for five days every three weeks). Response, defined as improvement in both clinical examination and computed tomography scan in absence of glucocorticoids dosage increase, was observed in three (17%) of 18 evaluable patients, lasting greater than 21, seven, and two months, respectively. Six additional patients had stable disease for greater than 10, seven, four, four, three, and two months: all of them had improvement of clinical symptoms but no variation in their scans. Overall median survival from the start of VP-16-213 was 4.5 months (range, 1-23 + months), whereas patients with response or stable disease had a median survival of eight months. Overall, treatment was well tolerated. In 10 patients concomitant plasma and cerebrospinal fluid samples were evaluated with a high-performance liquid chromatographic method for drug assay. The concentration of VP-16-213 in cerebrospinal fluid was less than 1% that found in plasma, even in the two patients with response. The activity of etoposide in patients with malignant, lomustine-vincristine-resistant brain tumors suggests an interesting potential use for this drug.


CD133/prominin-1-mediated autophagy and glucose uptake beneficial for hepatoma cell survival.
CD133/Prominin-1 is a pentaspan transmembrane protein that has been frequently used as a biomarker for cancer stem cells, although its biological function is unclear. The aim of our study was to explore the intrinsic functions of CD133 membrane protein in hepatoma cells during autophagy, apoptosis, tumorigenesis and cell survival through expression or downregulation of CD133. In this study, CD133 was found to be dynamically released from plasma membrane into cytoplasm in both of complete medium(CM) and low glucose medium (LGM), and LGM promoted this translocation. Expression of CD133 enhanced autophagic activity in LGM, while silencing CD133 attenuated this activity in HCC LM3 and Huh-7 cells, suggesting that CD133 is associated with autophagy. Immunofluorescence and time-lapsed confocal techniques confirmed that CD133 was associated with autophagy marker, microtubule-associated protein light chain3 (LC3) and lysosome marker during the glucose starvation. We further found that Huh-7 cells with stable expression of shCD133 (Huh-7sh133) impaired the ability of cell proliferation and formation of xenograft tumors in the NOD/SCID mice. Although loss of CD133 did not affect the rates of glucose uptake in Huh-7con and Huh-7sh133 cells under the CM, Huh-7sh133 cells obviously died fast than Huh-7con cells in the LGM and decreased the rate of glucose uptake and ATP production. Furthermore, targeting CD133 by CD133mAb resulted in cell death in HepG2 cells, especially in the LGM, via inhibition of autophagic activity and increase of apoptosis. The results demonstrated that CD133 is involved in cell survival through regulation of autophagy and glucose uptake, which may be necessary for cancer stem cells to survive in tumor microenvironment.


Management of post-operative subcutaneous emphysema with the application of wound VAC therapy.
Extensive subcutaneous emphysema (SE) complicates between 1 and 6% of elective thoracic procedures. The management of SE is varied, and may include increasing the suction of chest tubes, placement of additional chest tubes, placement of subcutaneous drains and creation of releasing incisions. We present five patients with post-operative SE treated successfully with a subcutaneous infraclavicular incision and wound VAC therapy. A 5-cm incision was made 2 cm below the clavicle down and through the pectoralis major fascia. A VAC dressing was fitted to the wound and suction was applied to -125 mm Hg. Data were retrospectively collected and analyzed. VAC dressing was placed a median of 6 days after initial operation. All patients had improvement in symptoms and resolution of SE by VAC dressing therapy. Subcutaneous infraclavicular incision and VAC dressing placement is a viable treatment for patients with post-operative SE who fail conservative therapy.


Retrieval of Brain Tumors by Adaptive Spatial Pooling and Fisher Vector Representation.
Content-based image retrieval (CBIR) techniques have currently gained increasing popularity in the medical field because they can use numerous and valuable archived images to support clinical decisions. In this paper, we concentrate on developing a CBIR system for retrieving brain tumors in T1-weighted contrast-enhanced MRI images. Specifically, when the user roughly outlines the tumor region of a query image, brain tumor images in the database of the same pathological type are expected to be returned. We propose a novel feature extraction framework to improve the retrieval performance. The proposed framework consists of three steps. First, we augment the tumor region and use the augmented tumor region as the region of interest to incorporate informative contextual information. Second, the augmented tumor region is split into subregions by an adaptive spatial division method based on intensity orders; within each subregion, we extract raw image patches as local features. Third, we apply the Fisher kernel framework to aggregate the local features of each subregion into a respective single vector representation and concatenate these per-subregion vector representations to obtain an image-level signature. After feature extraction, a closed-form metric learning algorithm is applied to measure the similarity between the query image and database images. Extensive experiments are conducted on a large dataset of 3604 images with three types of brain tumors, namely, meningiomas, gliomas, and pituitary tumors. The mean average precision can reach 94.68%. Experimental results demonstrate the power of the proposed algorithm against some related state-of-the-art methods on the same dataset.


[An ultrastructural study of capillary endothelial cells in toxemic placental villi using a quick quenching method].
The pathophysiological phenomena of placental microcirculation in cases of toxemia of pregnancy were studied. Fetal capillary endothelial cells, which were constituents of placental barrier, in chorionic villi from 5 normal and 10 toxemic pregnancies were ultrastructurally observed. The small pieces of tissue were prepared by a quick quenching & freeze substitution method, immediately after removal or after incubation in catecholamine solution. 1) In normal placentae, the thickness of the endothelial cells was uniform, and so was the distribution of cytoplasmic organelles. After incubation in catecholamine solution, endothelial cytoplasm partly protruded towards the capillary lumen, forming humps, which contained plenty of 6 nm diameter filaments which were thought to be actin filaments. 2) In toxemic placentae, 10nm diameter filaments increase to form bundles in endothelial cytoplasm. No cytoplasmic organelles were found here. Especially in placentae from severe toxemic pregnancies with IUGR, the augmentation of these filaments was so pronounced that the capillaries seemed as if they were solid molds, and it is possible that the blood flow is disturbed in these capillaries. 3) The endothelial cells occupied by bundles of filaments contained almost no organelles or pinocytotic vesicles. This fact suggests that the quantity of filaments affects the ability to actively transport the substances of mother and fetus.


Mucosal T cells bearing TCRgammadelta play a protective role in intestinal inflammation.
Intestinal intraepithelial lymphocytes (IEL) bearing TCRgammadelta represent a major T cell population in the murine intestine. However, the role of gammadelta IEL in inflammatory bowel diseases (IBD) remains controversial. In this study, we show that gammadelta IEL is an important protective T cell population against IBD. gammadelta T cell-deficient (Cdelta(-/-)) mice developed spontaneous colitis with age and showed high susceptibility to Th1-type 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis at a young age. Transfer of gammadelta IEL to Cdelta(-/-) mice ameliorated TNBS-induced colitis, which correlated with decrease of IFN-gamma and TNF-alpha production and an increase of TGF-beta production by IEL. Furthermore, a high level of IL-15, which inhibits activation-induced cell death to terminate inflammation, was expressed more in intestinal epithelial cells (EC) from TNBS-treated Cdelta(-/-) mice than in those from wild-type mice. EC from wild-type mice significantly suppressed the IFN-gamma production of IEL from TNBS-treated Cdelta(-/-) mice, whereas EC from TNBS-treated Cdelta(-/-) mice did not. These data indicate that gammadelta IEL play important roles in controlling IBD by regulating mucosal T cell activation cooperated with EC function. Our study suggests that enhancement of regulatory gammadelta T cell activity is a possible new cell therapy for colitis.


Polymorphous low-grade neuroepithelial tumor of the young: Rare tumor and review of the literature.
Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described low-grade neuroepithelial tumor with an infiltrative growth pattern and oligodendrocyte-like cells that are CD34 immunopositive. Correlating histology and results from molecular testing is critical to correctly diagnosing PLNTY, as its histologic appearance is similar to oligodendrogliomas and shares genetic abnormalities common to other low-grade epilepsy associated tumors (LEATs). In this case report, we describe a 31-year-old female with intractable epilepsy found to have a temporal mass and diagnosed with PLNTY after histopathologic and molecular testing. We describe the radiographic, histologic, and genetic features in relation to the epileptic and oncologic outcomes for this patient. Then, we compare these features and outcomes to other cases of PLNTY described in the literature.