Non-invasive intrapartum fetal ECG: preliminary report.
To obtain fetal heart rate, detailed fetal electrocardiography (fECG) signals and uterine contractions during labour using a single device. Prospective observational study. Delivery suite at a tertiary referral hospital, London, UK. Fifteen patients at median gestation of 39 weeks (range 24-41) were recruited at median cervical dilatation of 4.0 cm (range 0-10) of whom 8/15 (53%) had intact amniotic membranes. Using 12 abdominally sited electrodes, we recorded the composite abdominal signal in pregnancies intrapartum. The recorded data were analysed off-line using a blind signal separation technique. Success of signal separation and fECG time intervals. Successful fECG signal acquisition was achieved in 12/15 (80%) patients and an averaged fECG waveform acquired. In these patients, P and QRS waves were seen in all cases, and T waves in 11/12 (92%). True beat-to-beat heart rate (HR) was displayed and measures of its variability obtained. The mother's ECG and uterine electrical activity, shown to match tocographically recorded uterine contractions, were also separated and displayed. Failure to acquire fECG in three cases was attributed to excessive abdominal muscular activity and electrical interference. This study demonstrates a non-invasive technique that displays detailed intrapartum fECG waveforms, HR variability, maternal ECG and uterine contractions simultaneously, all in a single device and which avoids the potential risks of invasive monitoring with a fetal scalp electrode.


Effect of carbohydrate ingestion during cycling exercise on affective valence and activation in recreational exercisers.
Carbohydrate (CHO) ingestion enhances "feel-good" responses during acute exercise but no study has examined the effect of regular ingestion of CHO on affective valence. We investigated the effect of CHO ingestion on perceptual responses and perceived work intensity of individual exercise sessions throughout a 10-week cycling ("spin") exercise intervention. We also assessed whether any changes in affect and/or perceived work intensity would influence health and fitness parameters. Twelve recreational exercisers (46 ± 9 years; nine females and three males) were randomly allocated to either CHO (7.5% CHO; 5 mL · kg-1 per exercise session; n = 6; CHO) or placebo (0% CHO, taste- and volume-matched solution; n = 6; PLA) groups. Participants exercised 2 × 45-min per week, over a 10-week intervention period. Perceptual measures of exertion (RPE), affect (feeling scale, FS) and activation (felt arousal scale, FAS) were assessed after each exercise session. The FAS ratings increased over time in CHO but decreased throughout the intervention in PLA (P = 0.03). There were no differences in heart rate (P = 0.70), RPE (P = 0.05) and FS (P = 0.84) between trials. Furthermore, no changes in health and fitness parameters were observed over time or between groups. CHO ingestion enhanced ratings of activation in recreational exercisers throughout a 10-week cycling intervention.


Comparison of effectiveness between complete internal limiting membrane peeling and internal limiting membrane peeling with preservation of the central fovea in combination with 25G vitrectomy for the treatment of high myopic foveoschisis.
Vitrectomy combined with internal limiting membrane peeling (ILMP) treats high myopic foveoschisis with good results, but there is a risk of iatrogenic macular holes, which may be reduced by preserving the internal limiting membrane of the central fovea. This study compared complete ILMP with partial ILMP, both combined with 25G vitrectomy, for the treatment of high myopic foveoschisis.Thirty-three cases (33 eyes) of high myopic foveoschisis were retrospectively analyzed. They underwent 25G vitrectomy combined with C3F8 gas filling; Group A (20 patients, 20 eyes) underwent complete ILMP, while Group B (13 patients, 13 eyes) underwent partial ILMP to preserve the internal limiting membrane of the central fovea. Patients were followed up for 6 months and underwent best corrected visual acuity (BCVA), intraocular pressure, diopter, slit lamp microscopy, indirect ophthalmoscope, A-mode and/or B-mode ultrasound, and optical coherence tomography. Surgical complications were recorded.Up to the last follow-up, the BCVA improved and central fovea thickness (CFT) was lower compared with before surgery in both groups (All P < .05). There were no significant differences in BCVA and CFT at each time point between the groups (P > .05). Most of the postoperative retinas of the 2 groups were completely reattached, with disappearance of the macular retinoschisis cavity. Two patients in the Group A and none in the Group B developed a macular hole during follow-up (P = .508).The results did not support the superiority of partial ILMP over complete ILMP in reduced incidence of macular hole. Both methods had a similar curative effect.


Benign intracranial hypertension: atypical presentation of Miller Fisher syndrome?
Acute ocular paresis, nausea, vomiting, and headaches associated with high intracranial pressure without obvious intracranial pathology are typical features of benign intracranial hypertension. We describe two young children whose presentation, initially suggestive of idiopathic or benign intracranial hypertension, evolved to comprise ophthalmoplegia, ataxia, and areflexia. This triad characterizes Miller Fisher syndrome, a clinical variant of Guillain-Barré syndrome that occurs rarely among children. In both patients, this diagnosis was supported by the clinical course and neurophysiologic findings. Plasma serology was positive for Campylobacter jejuni and anti-GQ1b antibodies in one patient and for antimyelin antibodies in the other. This report of two children with Miller Fisher syndrome presenting with intracranial hypertension adds to the findings for a similar patient treated previously, which raises the question concerning the possible role or contribution of benign intracranial hypertension in Miller Fisher syndrome.


[Incorporation of 14-c-1-glycine into tissue proteins under the influence of insulin and its derivatives].
Effect of parenterally injected insulin and its composite sulpho-A- and B-chains on the rate of protein synthesis by the organs of the rat was investigated. It has been shown that insulin accelerates the incorporation of I-C14-glycine into proteins of the liver, kidneys, pancreas, spleen, sceletal muscules, thyroid gland, thymus and adrenal glands but does not influence this process in the cardiac muscle and diaphragm. A- and B-chains also activated protein metabolism in some organs, but despite some specificity of their action its extent was more limited as compared to that of insulin.


Protective roles of grape seed (Vitis vinifera L.) extract against cobalt(II) nitrate stress in Allium cepa L. root tip cells.
Excessive doses of toxic metals such as cobalt may cause detrimental hazards to exposed organisms. Six groups of onion bulbs were formed to investigate the therapeutic effects of grape seed extract (GSE) against cobalt(II) nitrate (Co(NO3)2) exposure in Allium cepa L. root tips. Control group was irrigated with tap water, while the latter groups were exposed to 150 mg/L GSE, 300 mg/L GSE, 5.5 ppm Co(NO3)2, 5.5 ppm Co(NO3)2 + 150 mg/L GSE and 5.5 ppm Co(NO3)2 + 300 mg/L GSE, respectively. Co(NO3)2 treatment seriously inhibited the root growth, germination and weight gain of the bulbs. Mitotic index was significantly decreased, whereas the chromosomal aberrations and micronuclei incidence exhibited a remarkable increase. In addition, Co(NO3)2 induced a variety of anatomical disorders in onion roots. Lipid peroxidation levels of the cellular membranes were assessed measuring the malondialdehyde content (MDA). MDA amount in Co(NO3)2-treated group reached the highest level among all groups. Co(NO3)2 treatment enhanced the activity of superoxide dismutase and catalase. The addition of GSE to Co(NO3)2 solution substantially suppressed the negative effects of Co(NO3)2 in a dose-dependent manner by strengthening the antioxidant defence system and reducing the cytotoxicity. Moreover, there was a significant recovery in growth parameters following the grape seed addition to Co(NO3)2. GSE had a remarkable reduction in genotoxicity when treated as a mixture with Co(NO3)2. Overall data obtained from this investigation proved that GSE, as a promising functional by-product, had a protective effect on Allium cepa L. against the toxic effects of Co(NO3)2.


Interictal pain in primary headache syndromes.
Primary headache disorders are generally characterized by the pain, time course, and associated symptoms of their attacks, but often are accompanied by milder interictal pain. Patients with chronic migraine, chronic tension-type headache, hemicrania continua, and new daily-persistent headache have constant pain more often than not. Patients with trigeminal autonomic cephalalgias such as cluster headache commonly have interictal pain as well, usually much milder and unilateral to the side of attacks. Even those with rare headache types, including hypnic headache and trigeminal neuralgia, commonly have interictal pain. This review describes the incidence of interictal pain in primary headache disorders and suggests the significance and biological meanings of this pain.


The Influence of Leg Length Discrepancy after Total Hip Arthroplasty on Function and Quality of Life: A Prospective Cohort Study.
We investigated whether patients with lengthening (> 9 mm), restoration (between 9 mm lengthening and 5 mm shortening) or shortening (> 5 mm) of the operated leg after total hip arthroplasty (THA) had different function (WOMAC score), quality of life (EQ-5D), residual hip pain, use of shoe lift and walking aid and leg length discrepancy (LLD) awareness, 12-15 months postoperatively. All patients had a significant postoperative improvement in WOMAC and EQ-5D regardless the LLD. However, the lengthening group showed less improvement in WOMAC, more use of shoe lift, residual hip pain and LLD awareness compared with the other two groups. No differences in EQ-5D were found. In spite of the improvement in function and quality of life, lengthening had adverse effects and should therefore be avoided.


Vitamin D(3) in fat tissue.
The literature describing vitamin D content of fat tissue is extremely limited. We conducted a pilot study that measured the concentrations of vitamin D(3) in the fat tissue and serum of obese adults. These measurements were performed using a new liquid chromatography mass spectrometry (LC/MS) method. The objectives of this study were: to measure and report the vitamin D(3) concentration in serum and subcutaneous fat samples from obese individuals and to examine the association of vitamin D(3) in fat with vitamin D(3) in serum. This cross-sectional study was conducted in 17 obese men and women who were scheduled to undergo gastric bypass surgery. The mean vitamin D(3) concentration in subjects' subcutaneous fat tissue samples was 102.8 +/- 42.0 nmol/kg. The mean vitamin D(3) concentration in serum was 7.78 +/- 3.99 nmol/l. Vitamin D(3) concentrations of fat tissue and serum were positively correlated (r = 0.68, P = 0.003). Consistent with previous findings in obese subjects, subjects in this study had suboptimal vitamin D status as demonstrated by a mean 25-hydroxyvitamin D concentration of 43.3 +/- 15.4 nmol/l. In conclusion, fat tissue vitamin D(3) can be measured by LC/MS and is detectable in obese subjects with suboptimal vitamin D status. Compatible with the long-standing concept that fat tissue is a storage site for vitamin D, fat tissue and serum vitamin D(3) concentrations were positively correlated.


Mid-term outcome following radial head arthroplasty in acute trauma: risk factors for poor outcome.
The aims of this study were to evaluate the outcomes of a single type of radial head implant in a large cohort of patients at mid-term follow-up and to determine the associated risk factors for inferior functional outcomes. We performed a retrospective follow-up assessment of 65 patients (33 women and 32 men; mean age, 53.3 years [range, 22-81 years]) who underwent radial head arthroplasty (RHA) for acute trauma between 2012 and 2018, after a minimum follow-up period of 3 years. The Mayo Elbow Performance Score, Oxford Elbow Score, Disabilities of the Arm, Shoulder and Hand score, and Mayo Modified Wrist Score were evaluated, and all available radiographs were analyzed. All complications and revision procedures were assessed. Bivariate and multivariate regression analyses were performed to identify potential risk factors for a poor outcome following RHA. After an average follow-up period of 4.1 years (range, 3-9.4 years), the mean Mayo Elbow Performance Score was 77.2 (standard deviation [SD], 18.9); mean Oxford Elbow Score, 32.0 (SD, 10.6); mean Mayo Modified Wrist Score, 74.6 (SD, 13.7); and mean Disabilities of the Arm, Shoulder and Hand score, 29.0 (SD, 21.2). Average range of motion measured 10° (SD, 15°) in extension, 125° (SD, 14°) in flexion, 81° (SD, 14°) in pronation, and 63° (SD, 24°) in supination. The overall complication and reoperation rates were 38.5% and 30.8%, respectively, with severe elbow stiffness being the most common reason for revision. Patient age >50 years, the use of an external fixator, the presence of accompanying medial collateral ligament injuries, and the development of higher-grade osteoarthritis were associated with a poor outcome. Satisfactory medium-term outcomes can be achieved using a monopolar, long-stemmed RHA in patients with acute trauma. However, complication and revision rates are high, frequently leading to inferior outcome scores. Additionally, a higher patient age, the use of an external fixator, the presence of accompanying medial collateral ligament injuries, and the occurrence of higher-grade osteoarthritis were associated with a poor outcome; these factors should raise awareness by the treating trauma surgeon.


ABCA1-mediated cholesterol efflux generates microparticles in addition to HDL through processes governed by membrane rigidity.
ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-poor apolipoprotein A-I (apoA-I) and generates HDL. Here, we demonstrate that ABCA1 also directly mediates the production of apoA-I free microparticles. In baby hamster kidney (BHK) cells and RAW macrophages, ABCA1 expression led to lipid efflux in the absence of apoA-I and released large microparticles devoid of apoB and apoE. We provide evidence that these microparticles are an integral component of the classical cholesterol efflux pathway when apoA-I is present and accounted for approximately 30% of the total cholesterol released to the medium. Furthermore, microparticle release required similar ABCA1 activities as was required for HDL production. For instance, a nucleotide binding domain mutation in ABCA1 (A937V) that impaired HDL generation also abolished microparticle release. Similarly, inhibition of protein kinase A (PKA) prevented the release of both types of particles. Interestingly, physical modulation of membrane dynamics affected HDL and microparticle production, rigidifying the plasma membrane with wheat germ agglutinin inhibited HDL and microparticle release, whereas increasing the fluidity promoted the production of these particles. Given the established role of ABCA1 in expending nonraft or more fluid-like membrane domains, our results suggest that both HDL and microparticle release is favored by a more fluid plasma membrane. We speculate that ABCA1 enhances the dynamic movement of the plasma membrane, which is required for apoA-I lipidation and microparticle formation.


Can a post-operative brace in slight hyperextension prevent extension deficit after anterior cruciate ligament reconstruction? A prospective randomised study.
It has been our observation that post-operative anterior cruciate ligament (ACL) braces together with the post-operative bandages do not always allow the knee to reach full extension. In ten uninjured knees with known hyperextension, the knees were bandaged in the same way as after an ACL-reconstruction. The knees were then studied radiologically in a Hypex brace set at 0 degrees, -5 degrees and -10 degrees of knee extension. Not a single knee was found to be straight in the brace set at 0 degrees. At -5 degrees most of the knees were straight or in slight hyperextension. It took -10 degrees to get all knees straight or in hyperextension. In a prospective randomised study 44 patients who underwent an arthroscopic ACL-reconstruction with a bone patellar tendon bone graft were randomised to use either a brace set at -5 degrees or a straight brace (0 degrees ) for at least the first three postoperative weeks. Before and three months after surgery range of motion was determined, using a goniometer with long arms, and sagittal knee laxity was measured with a KT-2000 arthrometer at manual max. Pre- and post-operative pain was evaluated with the Visual Analogue Scale (VAS). The same examiner (blindfolded to what type of brace was used) performed all the measurements. At three months, two of the 22 patients with the brace set at -5 degrees and twelve of the 22 patients with the straight brace had a loss of full extension of 2 degrees or more ( p<0.001). No significant differences were found between the groups in terms of knee flexion, sagittal knee laxity or post-operative pain. Although extension deficit after ACL-reconstruction can be prevented also in other ways, a Hypex brace set at -5 degrees seems to be an easy way of ensuring full knee extension.


Rapid 3D whole-heart cine imaging using golden ratio stack of spirals.
Three-dimensional cine imaging provides a wealth of information about cardiac anatomy and function, but its use in the clinical environment is limited because data acquisition is very time consuming. In this work, a free-breathing 3D whole-heart cine imaging framework was developed using a time-efficient stack of spirals trajectory and accelerated reconstruction. Two suitable view ordering methods are considered with different spacing between k-space readouts in the partition dimension: uniform and tiny golden ratio based. A simulation study suggested the latter did not present any benefits in terms of similarity to the true image. The proposed method was subsequently tested on 10 prospective subjects and compared with conventional multi-slice breath-hold imaging. Image quality was evaluated using objective and subjective scores and ventricular measurements were compared to assess clinical accuracy. Image quality was lower in the proposed technique than in breath-hold images but good agreement was found in clinically relevant ventricular measurements. In addition, the proposed method was fast to acquire, required minimal planning and provided full anatomical coverage with isotropic resolution.


Doxorubicin-induced co-assembling nanomedicines with temperature-sensitive acidic polymer and their in-situ-forming hydrogels for intratumoral administration.
Doxorubicin (DOX)-induced co-assembling nanomedicines (D-PNAx) with temperature-sensitive PNAx triblock polymers have been developed for regional chemotherapy against liver cancer via intratumoral administration in the present work. Owing to the formation of insoluble DOX carboxylate, D-PNAx nanomedicines showed high drug-loading and entrapment efficacy via a simple mixing of doxorubicin hydrochloride and PNAx polymers. The sustained releasing profile of D-PNA100 nanomedicines indicated that only 9.4% of DOX was released within 1day, and 60% was released during 10days. Based on DOX-induced co-assembling behavior and their temperature sensitive in-situ-forming hydrogels, D-PNA100 nanomedicines showed excellent antitumor activity against H22 tumor using intratumoral administration. In contrast to that by free DOX solution (1.13±0.04 times at 9days) and blank PNA100 (2.11±0.34 times), the tumor volume treated by D-PNA100 had been falling to only 0.77±0.13 times of original tumor volume throughout the experimental period. In vivo biodistribution of DOX indicated that D-PNA100 nanomedicines exhibited much stronger DOX retention in tumor tissues than free DOX solution via intratumoral injection. D-PNA100 nanomedicines were hopeful to be developed as new temperature sensitive in-situ-forming hydrogels via i.t. injection for regional chemotherapy.


Principles and application of oximetry.
The evaluation of oxygen availability, transport, and extraction at the tissue level have become critical factors in managing the acutely ill. Oximetry, both arterial and venous, has contributed to oxygenation assessments. Despite some limitations, oximetry offers immediate continuous feedback that can alert practitioners to potential oxygenation problems.


[Echographic studies of the paranasal sinuses].
On the basis of a literature review the author describes the use of the A-mode echography for examination of the paranasal sinuses. He concludes that echography is a useful additional investigation method for the evaluation of sinus pathology.


MLH1 rs1800734 Pathogenic Variant among Patients with Colorectal Cancer in the Lower Northeastern Region of Thailand.
The -93G > A (rs1800734) polymorphism within the core promoter region of MLH1 gene is associated with MLH1 CpG island hypermethylation. This polymorphism has recently been proposed as a low penetrance variant for colorectal cancer. Many published studies have evaluated the association between the MLH1 -93G > A polymorphism and colorectal cancer risk. However, the results remain conflicting rather than conclusive. The aim of this study was to assess the association between the MLH1 -93G > A polymorphism and the risk of colorectal cancer in patients with colorectal cancer in the lower northeastern region of Thailand. One hundred fifty one samples from colorectal cancer patients and 100 samples from healthy control group were analyzed. Genomic DNA was extracted from white blood cell of all samples. The real-time polymerase chain reaction (qPCR) was used to demonstrate genetic polymorphism of MLH1 rs1800734. This study demonstrated that the frequency of MLH1 rs1800734 in patients with colorectal cancer was higher than healthy control group. The MLH1 rs1800734 polymorphism variant AA was associated with an increased risk of colorectal cancer (p < 0.05). The MLH1 polymorphism variant AA carriers presented 1.36-folds high risk of colorectal cancer and the alcohol consumption was linked to their likelihood of developing colorectal cancer and their tumor's grade. This study showed that MLH1 rs1800734 genotype AA was associated with colorectal cancer risk in the lower northeastern region of Thailand.


Physical activity, inactivity and sleep during the Diabetes Remission Clinical Trial (DiRECT).
As sustained weight loss is vital for achieving remission of type 2 diabetes, we explored whether randomisation to weight loss plus maintenance in the DiRECT trial was associated with physical activity, inactivity or sleep. Participants were randomised to either a dietary weight management programme or best-practice care. The weight management group were encouraged to increase daily physical activity to their sustainable maximum. Objective measurement was achieved using a wrist-worn GENEActiv accelerometer for 7 days at baseline, 12 and 24 months in both groups. Despite average weight loss of 10 kg at 12 months in the intervention (n = 66) group, there were no differences in total physical activity or inactivity compared with the control (n = 104) at any time point. However, in our exploratory analysis, those who lost more than 10% of their baseline body weight performed on average 11 mins/day more light activity than the <10% group at 24 months (p = 0.033) and had significantly lower bouts of Inactivity30min (interaction, p = 0.005) across 12 and 24 months. At 24 months, the ≥10% group had higher daily acceleration (38.5 ± 12.1 vs. 33.2 ± 11.1 mg, p = 0.020), and higher accelerations in the most active 5-hour period (59.4 ± 21.8 vs. 50.6 ± 18.3 mg, p = 0.023). Wakefulness after sleep onset decreased in the intervention group compared with the control group and also in the ≥10% weight loss group at 12 and 24 months. Randomisation to a successful intensive weight loss intervention, including regular physical activity encouragement, was not associated with increased physical activity although sleep parameters improved. Physical activity was greater, and night-time waking reduced in those who maintained >10% weight loss at 12 and 24 months. TRIAL REGISTRATION ISRCTN03267836.


Oncogenes as novel targets for cancer therapy (part III): transcription factors.
This is the third paper in a four-part serial review on potential therapeutic targeting of oncogenes. The previous parts described the involvement of oncogenes in different aspects of cancer growth and development, and considered the new technologies responsible for the advancement of oncogene identification, target validation, and drug design. Because of such advances, new specific and more efficient therapeutic agents can be developed for cancer. This part of the review continues the exploration of various oncogenes that we have grouped within seven categories: growth factors, tyrosine kinases, intermediate signaling molecules, transcription factors, cell cycle regulators, DNA damage repair genes, and genes involved in apoptosis. Part one discussed growth factors and tyrosine kinases and part two discussed intermediate signaling molecules. This portion of the review covers transcription factors and the various strategies being used to inhibit their expression or decrease their activities.


Local anaesthetics attenuates spinal nociception and HPA-axis activation during experimental laparotomy in pigs.
The effect of local anaesthetics on spinal nociception and activation of the hypothalamic-pituitary-adrenal axis (HPA-axis) was examined in a porcine model of abdominal surgery. A standardised laparotomy without visceral involvement was performed on 24 pigs. One group received a unilateral infiltration of mixed lidocaine and bupivacaine in skin, muscle and peritoneum of the surgical area prior to surgery (n=12), while local anaesthetics were replaced by isotonic saline in a second group (n=12). A sham group was subjected to anaesthesia (n=8), but did not undergo surgery. Two hours after surgery, half of the pigs from each group were perfused with formalin and the spinal cord was taken out for stereological quantification of the total number of Fos-like-immunoreactive (Fos-LI) neurones in the dorsal horn. Surgery with saline gave rise to a significant increase in the number of Fos-LI neurones ipsilaterally (107,001+/-16,548; p<0.001) as well as contralaterally (12,766+/-3,842; p<0.01) compared to the sham group. In animals undergoing surgery with LA, the number of Fos-LI neurones ipsilaterally was not significantly different from the sham group (p=0.78), and was reduced significantly both ipsilaterally (6960+/-1662; p<0.001) and contralaterally (3974+/-1131; p<0.05) compared to the saline group. In the other half of each group, blood samples, for determination of ACTH, cortisol, C-reactive protein and interleukin-6 concentrations, were drawn prior to and at predetermined time-points during and after surgery. Surgery with saline gave rise to dramatic increases in plasma ACTH and cortisol (p<0.01 and p<0.001, respectively) within 15 min of incision. In contrast, no changes from the initial concentrations of ACTH and cortisol were observed in pigs receiving local anaesthetics. No changes in plasma concentrations of C-reactive protein or interleukin-6 were observed in either of the groups. These results indicate that spinal nociception and HPA-axis activation caused by laparotomy in pigs can be attenuated by use of infiltration and incisional local anaesthetics prior to surgery. The present model provides a valuable tool in the evaluation of analgesic treatment during surgery, offering objective measures of both nociception and stress.


Assessment of thrombogenic potential of liposomes.
The effects of liposomes with positive, neutral and negative surface charges on platelets and the plasmatic coagulation system were investigated in several in vitro and in vivo models. Negatively charged liposomes stimulated the plasmatic contact activating system as demonstrated by significant acceleration of whole blood clotting time measured in containers with nonwettable (siliconized) surface. The same liposomes induced reversible aggregates of human platelets in vitro and circulating reversible platelet aggregates after intravenous infusion in guinea pigs. Liposomes with positive and neutral surface charges had no effect on plasmatic coagulation and platelets. The biological mechanisms and the toxicological relevance of these findings are discussed.


Use of XTT for quantitating clonogenic growth in soft agar.
The purpose of this study was to investigate the use of the tetrazolium salt. XTT, in a microassay for quantitation of anchorage-independent growth of cells in soft agar, using two human ovarian tumour cell lines (OAW 42 and OAW 28). The response of OAW 42 to Cis-platinum, EGF, TGF β and insulin, and of OAW 28 to EGF, TGF β and insulin were determined both by visual colony counting and use of the XTT assay. Drug inhibition and growth factor inhibition and stimulation were clearly demonstrated, with increases or decreases in visually counted colony numbers being paralleled by increases or decreases in optical density values obtained by using XTT. The XTT colorimetric assay was simple to perform and reproducible with low variability, and was found to be an acceptable alternative to visual colony counting for the quantitation of cell line response to drugs and growth factors under anchorage-independent growth conditions.


Multivariate analysis of survival in inflammatory breast cancer: impact of intensity of chemotherapy in multimodality treatment.
The prognosis of inflammatory breast cancer (IBC) is poor. We evaluated clinical and biopathological characteristics that could affect survival in 74 women with nonmetastatic IBC consecutively treated in our institution between 1976 and 2000. Patients received primary anthracycline-based chemotherapy at conventional doses (n=20) or high-dose chemotherapy (HDC) with haematopoietic stem cell support (HSCS) (n=54). After chemotherapy, 84% of patients underwent mastectomy, 95% were given radiotherapy and 55% tamoxifen. Immunohistochemistry data (ER, PR, ERBB2, P53) on pre-chemotherapy specimens suggested strong differences between IBC and non-IBC. The rate of pathological complete response to chemotherapy was 26% (27% with HDC and 17% with conventional doses, not significant). No single factor was found predictive of response. With a median follow-up of 48 months after diagnosis, the 5-year projected disease-free survival (DFS) was 24% and overall survival (OS) 41%. In multivariate analysis, the strongest independent prognostic factor was the delivery of HDC. The 5-year DFS and OS of patients were respectively 28 and 50% with HDC and 15 and 18% with conventional chemotherapy. These results and comparisons with other series of patients suggest a role for HDC with HSCS as part of the therapeutic approach in IBC. Further prospective studies are required to confirm it.


Small molecule targeting of chromatin writers in cancer.
More than a decade after the launch of DNA methyltransferase and histone deacetylase inhibitors for the treatment of cancer, 2020 heralded the approval of the first histone methyltransferase inhibitor, revitalizing the concept that targeted manipulation of the chromatin regulatory landscape can have profound therapeutic impact. Three chromatin regulatory pathways-DNA methylation, histone acetylation and methylation-are frequently implicated in human cancer but hundreds of potentially druggable mechanisms complicate identification of key targets for therapeutic intervention. In addition to human genetics and functional screening, chemical biology approaches have proven critical for the discovery of key nodes in these pathways and in an ever-increasing complexity of molecularly defined human cancer contexts. This review introduces small molecule targeting approaches, showcases chemical probes and drug candidates for epigenetic writer enzymes, illustrates molecular features that may represent epigenetic dependencies and suggests translational strategies to maximize their impact in cancer therapy.


Changes in the microbial community after vaginal fluid exposure in different simulated forensic situations.
If vaginal fluid is found on clothing or on the body of the suspect, it may indicate the occurrence of sexual assault. Therefore, it is important to collect the victim's vaginal fluid at different sites from the suspect. Previous studies have revealed that fresh vaginal fluids can be identified based on 16S rRNA gene sequencing data. However, the influence of environmental factors on the stability of microbial markers must be investigated before being used in forensic practice. We collected vaginal fluid from nine unrelated individuals and placed each individual of vaginal swab on five different substrates. A total of 54 vaginal swabs were analyzed using 16S rRNA on the V3-V4 regions. Then, we constructed a random forest model including the samples of all vaginal fluids in this study and the other four types of body fluids in our previous studies. The alpha diversity of vaginal samples increased after exposure to the substrate environment for 30 days. The dominant vaginal bacteria were Lactobacillus and Gardnerella, which remained relatively stable after exposure, with Lactobacillus being the most abundant in all substrates, while Gardnerella was more abundant in other substrates than in the polyester fiber substrate. Except for bed sheets, Bifidobacterium significantly declined when placed on other substrates. Rhodococcus and Delftia from the substrate environment migrated to the vaginal samples. Rhodococcus was abundant in polyester fibers, and Delftia was abundant in wool substrates, while those environmental bacteria were all in low abundance in bed sheets. Overall, the bed sheet substrates showed a good retention capacity for the dominant flora and could reduce the number of taxa migrated by the environment compared with the other substrates. Both fresh and exposed vaginal samples of the same individuals could mostly be clustered and clearly distinguished from different individuals, showing the potential of individual identification, and the confusion matrix value of body fluid identification for vaginal samples was 1. In summary, vaginal samples placed on the surface of different substrates retained their stability and demonstrated good application potential for individual and body fluid identification.


2-Deoxy-D-Glucose Exhibits Anti-seizure Effects by Mediating the Netrin-G1-KATP Signaling Pathway in Epilepsy.
Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. The glycolytic inhibitor 2-deoxy-D-glucose (2-DG) has been reported to exert antiepileptic effects by upregulating KATP subunits (kir6.1 and kir6.2). We evaluated whether 2-DG exhibits anti-seizure effect by mediating the netrin-G1-KATP signaling pathway in epilepsy. In a mouse epilepsy model induced by lithium chloride-pilocarpine, 2-DG intervention increased the mRNA and protein expression levels of kir6.1 and kir6.2, and these increases were significantly reversed after knocking down netrin-G1 expression. Similarly, in cultured neurons with a magnesium-free medium, we found that the frequency of spontaneous postsynaptic potentials (SP) was increased, and in the meanwhile, expression levels of kir6.1 and kir6.2 were increased after pretreatment with 2DG. These effects were remarkably reversed after knocking down netrin-G1. Thus, our findings show that 2DG exhibits anti-seizure effects through the netrin-G1-KATP signaling pathway.


GHap: an R package for genome-wide haplotyping.
The GHap R package was designed to call haplotypes from phased marker data. Given user-defined haplotype blocks (HapBlock), the package identifies the different haplotype alleles (HapAllele) present in the data and scores sample haplotype allele genotypes (HapGenotype) based on HapAllele dose (i.e. 0, 1 or 2 copies). The output is not only useful for analyses that can handle multi-allelic markers, but is also conveniently formatted for existing pipelines intended for bi-allelic markers. https://cran.r-project.org/package=GHap firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Evaluation of Maternal Genetic Background of Two Hungarian Autochthonous Sheep Breeds Coming from Different Geographical Directions.
The aim of our research was the evaluation of the maternal genetic background of two Hungarian autochthonous sheep breeds of different geographical origin. A major argument for the preservation of endangered animal breeds is their documented past and historical importance. These also include the registration of pedigree data. This is the first study to evaluate and compare Tsigai and Cikta sheep in Hungary. Our investigation is based on two complete sequences of mitochondrial DNA (cytochrome b gene and control region). Our research was performed on these two sheep breeds with markedly different breed histories and breed characteristics to determine a possible common maternal genetic background, as ultimately the origin of both breeds can be traced back to Asia Minor. Between 2015 and 2017, a total of 203 biological samples were taken using a newly introduced founder sampling method. We found that the prevailing haplogroup B accounted for over 80% of both breeds, strengthening the common ancestral root. However, the pairwise genetic differentiation estimates (KST) calculated using the sequence-based statistics for cytochrome b gene and control region were 0.034 and 0.021, respectively (both at level p < 0.05); thus, revealing genetic differentiation in both sequences between the Tsigai and Cikta. We note that the known different history of the breeds is clearly justified by the currently studied deviations in their maternal genetic background.


Induction of parturition in dairy heifers using prostaglandin F2alpha.
Prostaglandin was used to induce parturition in three trials on two farms, involving 55 Friesian heifers. Calf viability, dystocia, percentage retained placenta, induction interval and colostrum absorbtion (in 18 cases) are discussed.


[Therapeutic progress in malignant testicular neoplasms].
Besides the progress of surgical and radiological regimens it is a new approach in cytostatic chemotherapy which has improved the prognosis of testicular tumours. Combination chemotherapy results in a 70 to 100% remission rate and a prolonged duration of survival.


Mode of action of carbimazole in Graves' disease.
In a series of hyperthyroid subjects treated with a high dose 'block-replace' regime, mean thyroidal technetium uptake was shown to fall progressively over an 18 month period. Furthermore, sub-total inhibition of hormone biosynthesis could be demonstrated, without evidence of proportionate inhibition of organification, the regression of radio-iodine on technetium thyroid uptake showing similar slopes in euthyroid, treated and untreated hyperthyroid subjects. Together with the reported differential in remission rates between propranolol and anti-thyroid drugs, it is concluded that carbimazole does not act solely by inhibiting intrathyroid hormono-genesis, but more definitively by affecting thyroid hyperstimulation at a pre-biosynthetic level. The inability to demonstrate normal suppressibility of trapping in any subject in the present series despite extended therapy with a 'block-replace' regime, further suggests that current concepts of 'suppressibility' are invalid, the progressive fall in technetium uptake being unlikely to represent spontaneous restoration of a normal pituitary-thyroid axis, but rather a direct influence or prolonged therapy with anti-thyroid drugs on the natural history of the disease.


Biosynthesis of eriodictyol from tyrosine by Corynebacterium glutamicum.
Eriodictyol is a bioactive flavonoid compound that shows potential applications in medicine development and food processing. Microbial synthesis of eriodictyol has been attracting increasing attention due to several benefits. In this study, we employed a GRAS strain Corynebacterium glutamicum as the host to produce eriodictyol directly from tyrosine. We firstly optimized the biosynthetic module of naringenin, the upstream intermediate for eriodictyol production, through screening of different gene orthologues. Next, to improve the level of the precursor malonyl-CoA necessary for naringenin production, we introduced matB and matC from Rhizobium trifolii into C. glutamicum to convert extracellular malonate to intracellular malonyl-CoA. This combinatorial engineering resulted in around 35-fold increase in naringenin production from tyrosine compared to the initial recombinant C. glutamicum. Subsequently, the hpaBC genes from E. coli encoding 4-hydroxyphenylacetate 3-hydroxylase were expressed in C. glutamicum to synthesize eriodictyol from naringenin. Further optimization of the biotransformation process parameters led to the production of 14.10 mg/L eriodictyol. The biosynthesis of the ortho-hydroxylated flavonoid eriodictyol in C. glutamicum was achieved for the first time via functional expression of E. coli hpaBC, providing a baseline strain for biosynthesis of other complex flavonoids. Our study demonstrates the potential application of C. glutamicum as a host microbe for the biosynthesis of value-added natural compounds from tyrosine.


The clinical and functional outcome after restorative proctocolectomy. A prospective study in 100 patients.
One hundred consecutive patients treated by restorative proctocolectomy with construction of an ileo-anal anastomosis and a J-shaped (n = 90) or an S-shaped ileal reservoir were studied prospectively to evaluate postoperative complications and functional outcome and to search for factors that might influence results. There were no deaths. Postoperative complications requiring surgery were pelvic sepsis (3 patients), pouch-related fistula (2), peritonitis following ileostomy closure (3) and small bowel obstruction (6), with an overall relaparotomy rate of 14%. The cumulative risk of pouchitis was 30% at 2 years. The average stool frequency decreased gradually, stabilizing at about five evacuations/24 h after 1 year. At that time 9% of patients still had greater than or equal to 7 day-time evacuations and 40% had night evacuations (greater than 1/week). These parameters did not improve further with time. Mucous soiling, a frequent problem initially, also diminished with time, occurring in 30% of patients at 1 year. At 2 years, however, this mucous leak occurred in only 20%, suggesting that improvement of continence can be expected to occur even beyond one year. Despite defects in function patient satisfaction was generally excellent. So far only three patients have preferred conversion to an ileostomy. To establish which factors might influence the functional results a specially designed scoring system, combining all functional variables, was used. It was shown that results deteriorated with increasing age and that elderly women tended to have a poorer result than elderly men. Sex, previous parity or postoperative complications appeared not to affect the functional outcome. Male sexual disturbances occurred in 8%.(ABSTRACT TRUNCATED AT 250 WORDS)


Ion regulation in the different life stages of Trypanosoma cruzi.
Different ion and pH regulation mechanisms have been detected in the three main life stages of Trypanosoma cruzi: epimastigote, metacyclic trypomastigote and amastigote. Treatment with amiloride showed that the Na(+)/H(+) exchanger participated in all three forms. The Na(+)/K(+) ATPase exchanger appeared to be more active in the epimastigote than in the other forms. V-H(+)-ATPase inhibitors revealed the activity of this regulatory mechanism in the amastigote and epimastigote forms, while treatment with oligomycin only affected the amastigotes. The HCO(-)(3)/Cl(-) exchanger was found in all stages as well as in the intracellular pH-regulatory mechanism after abrupt basification. We deduce that ion regulation in T. cruzi is a complex process and depends upon the precise stage of the cell cycle of the parasite. It would seem to be an important mechanism, allowing the parasite to adapt to the changing environmental conditions within which it develops.


Developmental Patterning: Putting the Squeeze on Mis-specified Cells.
Widely implicated in human disease, abnormal cellular cysts reflect dramatic defects in the maintenance of epithelial integrity. A new study reports that epithelial cysts may arise as a surprisingly general consequence of clonal defects in the specification of cell identity.


Current synthesis and characterization techniques for clay-based polymer nano-composites and its biomedical applications: A review.
Clays and its composites have received considerable attention recently due to their low cost, wide availability and low environmental impact. The development of various preparation processes and applications of innovative polymer-nanoclay composites has been aided by recent breakthroughs in material technologies. Novel polymer-nanoclay composites with better qualities have been effectively adopted in a variety of fields, including aerospace, car, construction, petroleum, biomedical, and wastewater treatment, owing to innovative production processes. Due to their superior qualities, such as increased density, strength, relatively large surface areas, high elastic modulus, flame retardancy, and thermomechanical/optoelectronic/magnetic capabilities, these composites are acknowledged as potential advanced materials. Hence the present paper reviews the advances in synthesis and preparation of clay-polymer nanocomposites. In addition, this study also focuses on the various techniques used for clay-polymer nanocomposites characterization e.g. scanning electron microscope (SEM), transmission electron microscope (TEM), thermo-gravimetric analysis (TGA) and differential colorimetric analysis (DSC), x-ray diffraction (XRD) analysis, Nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopic (FTIR) characterization. These advanced physico-mechanical and chemical characterization techniques would be effective in understanding the most appropriate application of clay polymer nanocomposites. In addition, the application of clay polymer nanocomposites in biomedical sector is also discussed in brief.


Evaluation of machine learning approaches for prediction of pigeon pea yield based on weather parameters in India.
Pigeon pea is the second most important grain legume in India, primarily grown under rainfed conditions. Any changes in agro-climatic conditions will have a profound influence on the productivity of pigeon pea (Cajanus cajan) yield and, as a result, the total pulse production of the country. In this context, weather-based crop yield prediction will enable farmers, decision-makers, and administrators in dealing with hardships. The current study examines the application of the stepwise linear regression method, supervised machine learning algorithms (support vector machines (SVM) and random forest (RF)), shrinkage regression approaches (least absolute shrinkage and selection operator (LASSO) or elastic net (ENET)), and artificial neural network (ANN) model for pigeon pea yield prediction using long-term weather data. Among the approaches, ANN resulted in a higher coefficient of determination (R2 = 0.88-0.99), model efficiency (0.88-1.00) with subsequent lower normalised root mean square error (nRMSE) during calibration (1.13-12.55%), and validation (0.33-21.20%) over others. The temperature alone or its interaction with other weather parameters was identified as the most influencing variables in the study area. The Pearson correlation coefficients were also determined for the observed and predicted yield. Those values also showed ANN as the best model with correlation values ranging from 0.939 to 0.999 followed by RF (0.955-0.982) and LASSO (0.880-0.982). However, all the approaches adopted in the study were outperformed the statistical method, i.e. stepwise linear regression with lower error values and higher model efficiency. Thus, these approaches can be effectively used for precise yield prediction of pigeon pea over different districts of Karnataka in India.


Conventional therapy and approach to management.
The treatment of multiple myeloma (MM) has undergone major changes in the last decade. There is now an array of therapeutic options, including autologous stem-cell transplantation, non-myeloablative (mini) allogeneic transplantation, and new drugs such as thalidomide and bortezomib. There is also an awareness that there are subsets of patients with MM who have not gained much from the recent advances, including patients with certain adverse prognostic factors (high-risk MM). In this article, we outline our approach to the diagnosis, risk stratification and treatment of MM with a focus on conventional therapy. We incorporate a risk-based strategy for the treatment of MM that also takes into account the eligibility of the patient to undergo stem-cell transplantation. We also outline the role and current indications for the use of new active agents in this disease.


Salivary gland immunization via Wharton's duct activates differential T-cell responses within the salivary gland immune system.
Salivary glands are a major component of the mucosal immune system that confer adaptive immunity to mucosal pathogens. As previously demonstrated, immunization of the submandibular gland with tissue culture-derived murine cytomegalovirus (tcMCMV) or replication-deficient adenoviruses expressing individual murine cytomegalovirus (MCMV) genes protected mice against a lethal MCMV challenge. Here, we report that salivary gland inoculation of BALB/cByJ mice with tcMCMV or recombinant adenoviruses differentially activates T helper (Th)1, -2, and -17 cells in the salivary glands vs. the associated lymph nodes. After inoculation with tcMCMV, lymphocytes from the submandibular gland preferentially express the transcription factor T-cell-specific T-box transcription factor (T-bet), which controls the expression of the hallmark Th1 cytokine, IFN-γ. Lymphocytes from the periglandular lymph nodes (PGLNs) express both T-bet and GATA-binding protein 3 (GATA3), which promotes the secretion of IL-4, -5, and -10 from Th2 cells. In contrast, after inoculation with replication-deficient adenoviruses, lymphocytes from the submandibular gland express T-bet, GATA3, and RAR-related orphan receptor γ, thymus-specific isoform (RORγt) (required for differentiation of Th17 cells) and forkhead box P3 (Foxp3) (required for the differentiation of regulatory T cells). Lymphocytes from the PGLNs were not activated. The differential induction of Th responses in the salivary gland vs. the PGLNs after inoculation with attenuated virus vs. a nominal protein antigen supports the use of the salivary as an alternative mucosal route for administering vaccines.-Liu, G., Zhang, F., Wang, R., London, S. D., London, L. Salivary gland immunization via Wharton's duct activates differential T-cell responses within the salivary gland immune system.


Inhibition of temperature-induced spermatogenic proliferation by a brain factor in hibernating Helix aspersa (Mollusca).
Ablation of the brain from hibernating Helix aspersa maintained at 25 degrees C causes a significant increase in the proliferation of male cells in the gonad, whereas the ablation of the optic tentacles has no effect. The brain, therefore, produces a factor which specifically inhibits the multiplication of spermatogonia and spermatocytes.


Synthesis and cytotoxicity evaluation of biaryl-based chalcones and their potential in TNFα-induced nuclear factor-κB activation inhibition.
A series of biaryl-based chalcones were designed as a combination of the natural chalcone and biphenyl moieties, and synthesized by two step chemistry involving Knoevenagel reaction and microwave assistant Suzuki coupling. Sulforhodamine B (SRB) assay was performed to evaluate the cell viability inhibitory abilities of these compounds against five cancer cell lines (A549, CNE2, SW480, MCF-7, and HepG2) from different tissues. Their Nuclear Factor-κB (NF-κB) nuclear translocation inhibitory activities were further investigated by High Content Analysis (HCA) based assay. Most of the compounds showed moderate to strong anticancer and NF-κB nuclear translocation inhibition activities and potent compounds were found.


Factors affecting the decision to undergo risk-reducing salpingo-oophorectomy among women with BRCA gene mutation.
The objective of this study was to identify factors that affect the decision to undergo risk-reducing salpingo-oophorectomy (RRSO) in BRCA1 or BRCA2 mutations carriers in South Korea. The medical records of 124 women who had been found to have BRCA1 or BRCA2 gene mutation at our institution between May 2003 and December 2011 were reviewed. The carriers were divided into RRSO and non-RRSO groups for comparison of their clinicopathologic, socio-economic, and psychosocial factors. Of the 71 carriers eligible for RRSO, 21 had undergone RRSO. In univariate analysis, classification of carriers into 3 groups by decade of life (4th, 5th, or 6th and later decade) and subsequent analysis revealed that 52.6% of carriers in the 5th decade had undergone RRSO, a rate significantly higher than that of the other age groups (p = 0.007). The RRSO rate was higher in carriers with a personal history of breast cancer than in those without (39.2% vs. 5.0%, p = 0.004), in carriers with a family history of breast cancer than in those without (35.5% vs. 11.8%, p = 0.065), and in carriers with a family history of ovarian cancer than in those carriers without a family history (66.7% vs. 24.2%, p = 0.016). Multivariate analysis identified age and personal history of breast cancer as independent factors affecting the decision to undergo RRSO. Age and personal history of breast cancer are important factors in the decision to undergo, and should thus be considered when counseling BRCA1/2 mutation carriers.


The Veterans Affairs Precision Oncology Data Repository, a Clinical, Genomic, and Imaging Research Database.
The Veterans Affairs Precision Oncology Data Repository (VA-PODR) is a large, nationwide repository of de-identified data on patients diagnosed with cancer at the Department of Veterans Affairs (VA). Data include longitudinal clinical data from the VA's nationwide electronic health record system and the VA Central Cancer Registry, targeted tumor sequencing data, and medical imaging data including computed tomography (CT) scans and pathology slides. A subset of the repository is available at the Genomic Data Commons (GDC) and The Cancer Imaging Archive (TCIA), and the full repository is available through the Veterans Precision Oncology Data Commons (VPODC). By releasing this de-identified dataset, we aim to advance Veterans' health care through enabling translational research on the Veteran population by a wide variety of researchers.


Involvement of neurotransmitters in urocortin-induced passive avoidance learning in mice.
The action of urocortin on one-way passive avoidance learning was tested in mice. Urocortin was administered into the lateral brain ventricle and the latency of the passive avoidance response was measured 24 h later. For study of the roles of various neurotransmitters in mediating the action of urocortin on the consolidation of memory, the animals were pretreated with different receptor antagonists. Urocortin facilitated the acquisition, consolidation and also retrieval of the passive avoidance response. The following receptor antagonists blocked the action of urocortin on consolidation: haloperidol, atropine, phenoxybenzamine, bicuculline, the CRF antagonist CRF9-41 and methysergide. Propranolol attenuated, but did not fully block the action of urocortin, while naloxone and nitro-L-arginine were ineffective. The results obtained demonstrate that urocortin is able to improve learning and memory and also retrieval processes in a passive avoidance learning in mice. D2, muscarinic cholinergic, alfa-adrenergic, CRF, serotonergic (5HT 1-2), GABA B receptors are involved in the consolidation of the passive avoidance response.


The diagnostic role of PD-1+ CXCR5+ follicular helper CD8+ T cell in renal allograft dysfunction.
The roles of PD-1+ CXCR5+ follicular helper CD8+ T cell were reported in different disease conditions, but their roles in transplantation are unclear. In this study, the association between PD-1+ CXCR5+ follicular helper CD8+ T cell and renal allograft dysfunction in kidney transplant recipients (KTRs) was investigated. 82 KTRs were enrolled in this study. 45 KTRs were included in the chronic allograft dysfunction (CAD) group, and 37 KTRs were included in the stable recipients group. Among the CAD group, 12 cases of antibody-mediated rejection (ABMR) and 4 cases of T cell-mediated rejection (TCMR) were diagnosed by biopsy. The percentage of CXCR5+ CD8+ T cells and the co-expression of signal transducers and activators of transcription 4 (STAT4), STAT5, and PD-1 in peripheral blood were determined by flow cytometry. The expression of CXCR5 on CD3+ CD8+ T cells and the percentage of STAT5+ CXCR5+ cells in the CD3+ CD8+ T-cell population were significantly lower in the CAD group (p < 0.05), while the expression of PD-1+ CXCR5+ CD8+ T cells was significantly higher (p < 0.05). Through logistic regression analysis, we concluded that the percentage of PD-1+ CXCR5+ CD8+ T cells was an independent risk factor for renal dysfunction. Grouping by pathological type, PD-1+ CXCR5+ CD8+ T cells showed relatively good diagnostic efficacy for ABMR by ROC analysis. Our results suggested that PD-1+ CXCR5+ CD8+ T cells were a promising biomarker for distinguishing renal allograft dysfunction and different allograft pathological types. Also, our findings may provide new ways of identifying and treating allograft rejection.


Comparative cognition: Capuchin monkeys believe in magic.
Capuchin monkeys are unique among New World monkeys for their manual dexterity and use of tools. New research using magical sleight of hand shows visual perception of others' actions paralleling their manual skills.


The frequency of kidney and urinary tract diseases in a defined population.
The frequencies of kidney and urinary tract diseases (KUTD) in a defined population are presented. Rates of first hospitalizations with KUTD in the 5-year period, 1971 through 1975, were determined among over 1 million members of the Kaiser Foundation Health Plan (KFHP) of Northern California. Cases were identified from computer-stored ICDA-coded final discharge diagnoses for hospitalizations. Kidney and other urinary tract diseases were final diagnoses in 35.7 first hospitalizations per 10,000 members per year in the period 1971 through 1975. Disease-specific rates were highest for urinary tract infections, benign prostatic hypertrophy, and renal and ureteral calculi. The frequency of KUTD in this population is compared to available rates from other sources.


Gas at abdominal US: appearance, relevance, and analysis of artifacts.
To describe the spectrum of ultrasonographic (US) appearances of intraluminal gas, including two clinically relevant gas artifacts. Observations were made in patients and reproduced in an animal model, an ex vivo gut preparation, and a tissue-mimicking phantom. Appearances were classified according to a physical model of the interaction between sound and collections of gas. Free bubbles of gas appeared as bright echogenic foci extending artifactually owing to lateral and axial blooming. This causes bubbles that abut the gut wall to enhance the layer one echo, which corresponds to the interface between the mucosa and the luminal contents. Such bubbles can also falsely appear to be within the gut wall itself owing to elevation averaging and thereby cause the artifact pseudo-pneumatosis intestinalis. Isolated groups of small bubbles created a characteristic periodicity and tapering of the distal echo pattern. In the extreme case, in which many such echoes are superimposed, "dirty shadowing" occurs. A contiguous pocket of gas may cause the gut wall to appear artifactually thickened (i.e., pseudo-thickened gut). This was shown to be a form of mirror image artifact. Classification of the effects of gas on US images according to their physical characteristics may aid in their interpretation. Appreciating two previously undescribed artifacts, pseudo-pneumatosis intestinalis and pseudo-thickened gut, will improve the usefulness of abdominal US.


Noncollagenous matrix proteins controlling mineralization; possible role in pathologic calcification of vascular tissue.
Biomineralization is a highly controlled process that is believed to be regulated by noncollagenous proteins found in the organic matrix of bone. Dystrophic calcification possesses several features of bone, including the presence of noncollagenous proteins, which are also thought to regulate pathologic calcification. Noncollagenous proteins have been demonstrated to be present in a wide variety of tissues. They are also believed to play a role in the pathogenesis of a number of disease processes, including atherosclerosis, restenosis, valvular stenosis, nephrolithiasis, glomerulonephritis, malignant transformation, and metastasis. This review discusses the structure, function, and possible roles of noncollagenous proteins in physiologic and pathologic processes.


A new calicivirus isolated from a marine mammal.
A new serotype of calicivirus, designated as San Miguel sea lion virus type 6 (SMSV-6), was isolated from vesicular lesions on the flipper of a California sea lion pup. Serologic studies show that SMSV-6 neutralizing antibodies (SN) occur frequently among California sea lions and occasionally among northern fur seals. Feral swine, 1- to 6-week elephant seal pups and grey whales tested negative for SMSV-6 antibody.


[Differential gene expression of liver carcinoma cell after transfection of by ARL-1 with microarray].
To study the difference of the gene expression profile and to identify the different expression after transfection of the ARL-1 gene. The cDNA probes were synthesized from total RNA of study group and control group, which was differentially hybridized to cDNA chips and confirmed by a gene specific semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Six kinds of gene expression were increased and 9 kinds of gene expression were decreased. The findings were correlated with protein metabolism, signal pathway, metastasis, and drug resistance. cDNA chips showed that gene expression profile of liver carcinoma cell was changed after transfection of the ARL-1 gene. It is a useful method in understanding the mechanism of drug resistance.


[Characteristic manifestations of neuropsychiatric systemic lupus erythematosus].
To investigate the characteristic manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE) in clinical practice. A total of 198 NPSLE cases from 1998 to 2003 in Peking Union Medical College Hospital, were included. Their clinical manifestations and the results of accessory examination such as serology, lumbar puncture, head magnetic resonance imaging, and electroencephalogram were analyzed. The most frequent manifestations of the NPSLE included: headache, psychiatric disorder, seizure, stroke, and acute confusional state. Fifty-two patients took head magnic resonance imaging, and 34 of them showed abnormal, including stroke attack. Among 48 patients who only had a complaint of headache, the increase of intracranial pressure and cerebral spinal fluid protein was significantly higher than other NPSLE syndromes (P < 0.05). Diagnosis of NPSLE was mainly based on its clinical manifestations. Head magnetic resonance imaging and cerebral spinal fluid examination may be helpful. More specific accessory examinations require further development.


Effect of the menstrual cycle and oral contraceptives on cyclooxygenase-2 expression in the endometrium.
To compare the expression of cyclooxygenase-2 (COX-2) and proliferation markers (Ki-67) in the endometrium of patients with ovulatory cycles with those in the endometrium of patients using oral contraceptives. Endometrial biopsies from 104 premenopausal patients with regular ovulatory cycles (n=90) or using an oral contraceptive (n=14) were selected for this study. Using immunohistochemical methods, both COX-2 (Novocastra clone 4H12) and Ki-67 (Dako clone MIB-1) expression were determined in the endometrium during the various phases of the menstrual cycle or following the use of oral contraceptives. COX-2 expression in the glandular epithelium was maximal during menstruation, the late proliferative phase and the early luteal phase, and minimal during the late luteal phase. However, in the surface epithelium, COX-2 expression remained strongly positive throughout the luteal phase. Ki-67 positivity increased during the proliferative phase and diminished during the luteal phase in the glands. In contraceptive users, both Ki-67 and COX-2 expression in the endometrium was low. The increased expression of COX-2 during menstruation and at mid-cycle is eliminated by the continuous use of oral contraceptives. This may be the rationale for their therapeutic action in the treatment of dysmenorrhea and bleeding.


Color-neutral, semitransparent organic photovoltaics for power window applications.
Semitransparent organic photovoltaic cells (ST-OPVs) are emerging as a solution for solar energy harvesting on building facades, rooftops, and windows. However, the trade-off between power-conversion efficiency (PCE) and the average photopic transmission (APT) in color-neutral devices limits their utility as attractive, power-generating windows. A color-neutral ST-OPV is demonstrated by using a transparent indium tin oxide (ITO) anode along with a narrow energy gap nonfullerene acceptor near-infrared (NIR) absorbing cell and outcoupling (OC) coatings on the exit surface. The device exhibits PCE = 8.1 ± 0.3% and APT = 43.3 ± 1.2% that combine to achieve a light-utilization efficiency of LUE = 3.5 ± 0.1%. Commission Internationale d'eclairage chromaticity coordinates of (0.38, 0.39), a color-rendering index of 86, and a correlated color temperature of 4,143 K are obtained for simulated AM1.5 illumination transmitted through the cell. Using an ultrathin metal anode in place of ITO, we demonstrate a slightly green-tinted ST-OPV with PCE = 10.8 ± 0.5% and APT = 45.7 ± 2.1% yielding LUE = 5.0 ± 0.3% These results indicate that ST-OPVs can combine both efficiency and color neutrality in a single device.


Identification of a cDNA encoding for Ghrelin in the testis of the frog Pelophylax esculentus and its involvement in spermatogenesis.
GHRELIN (GHRL) is an acylated peptide that contains 28-amino acids prevalently expressed in the stomach of several species. Specifically, it contributes to energy balance, but some new evidence highlights its role in the regulation of reproductive functions. In fact, this protein has been detected at testicular level in the tubular and interstitial compartments of several vertebrate species, and previous research has demonstrated that GHRL affects various aspects of spermatogenesis and steroidogenesis. GHRL clearly plays an inhibitory role in mammalian reproduction, in contrast GHRL stimulates reproductive functions in non mammalian vertebrate. We have focused our attention on the comparative aspect of GHRL, thus studying its expression in an amphibian seasonal breeder, Pelophylax esculentus, to verify the presence and localization, of Ghrl transcript variations during the frog reproductive cycle, in order to demonstrate that Pelophylax esculentus may represent a useful animal model to assess the role of GHRL in male fertility.


Accurate Sequencing and Haplotyping from 10 Cells Using Long Fragment Read (LFR) Technology.
In this chapter, we describe how Long Fragment Read (LFR) technology can be applied to samples consisting of very few cells (5-20) to enable complete genome sequencing and haplotyping with a very low false positive error rate. LFR is a method for processing DNA or cells prior to sequencing on any second-generation DNA sequencing platform (e.g., MGI's DNBSEQ, Illumina sequencers, etc.). First, the LFR process incorporates a low-bias whole genome amplification step allowing accurate sequencing from very low DNA inputs (as low as 32 picograms, the mass contained within 5 diploid human cells). In addition, LFR enables the haplotyping of nearly all genomic variations with N50 contig lengths up to ~1 Mb. Furthermore, if data from this method are analyzed with parental genotype data, it is possible to generate phased variants in uninterrupted contigs spanning entire chromosomes. Importantly, the barcoding process utilized in this method allows for the detection and correction of most amplification, sequencing, and mapping errors, yielding false positive error rates as low as 10-9. Finally, the cost of this method is modest and enables extremely high-quality whole genome sequence and haplotype data from as few as 5 cells. We know of few other methods that can achieve this.


Screening of Bothrops snake venoms for L-amino acid oxidase activity.
Toxins, enzymes, and biologically active peptides are the main components of snake venoms from the genus Bothrops. Following the venom inoculation, the local effects are hemorrhage, edema, and myonecrosis. Nineteen different species of Brazilian Bothrops were screened for protein content and L-amino acid oxidase activity. B. cotiara, formerly found in the South of Brazil, is now threatened with extinction. Its venom contains a highly hemorrhagic fraction and, as expected from the deep yellow color of the corresponding lyophilized powder, a high L-amino acid oxidase (LAO) activity was also characterized. Flavin adenine dinucleotide (FAD) is its associate coenzyme. B. cotiara venom LAO catalyzed the oxidative deamination of several L-amino acids, and the best substrates were methionine, leucine, tryptophan, and phenylalanine, hence, its potential application for the use of biosensors for aspartame determination and for the removal of amino acids from plasma. High levels for LAO were also found in other species than B. cotiara. In addition, the technique of isoelectric focusing (IEF) was employed as a powerful tool to study the iso- or multi-enzyme distribution for LAO activity in the B. cotiara snake venom.


Overestimated lead times in cancer screening has led to substantial underestimation of overdiagnosis.
Published lead time estimates in breast cancer screening vary from 1 to 7 years and the percentages of overdiagnosis vary from 0 to 75%. The differences are usually explained as random variations. We study how much can be explained by using different definitions and methods. We estimated the clinically relevant lead time based on the observed incidence reduction after attending the last screening round in the Norwegian mammography screening programme. We compared this estimate with estimates based on models that do not take overdiagnosis into account (model-based lead times), for varying levels of overdiagnosis. Finally, we calculated overdiagnosis adjusted for clinical and model-based lead times and compared results. Clinical lead time was about one year based on the reduction in incidence in women previously offered screening. When overdiagnosed tumours were included, the estimates increased to 4-9 years, depending on the age at which screening begins and the level of overdiagnosis. Including all breast cancers detected in women long after the end of the screening programme dilutes the level of overdiagnosis by a factor of 2-3. When overdiagnosis is not taken into account, lead time is substantially overestimated. Overdiagnosis adjusted for model-based lead time is a function tending to zero, with no simple interpretation. Furthermore, the estimates are not in general comparable, because they depend on both the duration of screening and duration of follow-up. In contrast, overdiagnosis adjusted for clinically relevant tumours is a point estimate (and interpreted as percentage), which we find is the most reasonable method.


Successfully treated postbronchoplasty bronchial stenosis using short-interval repeated endobronchial balloon dilation.
A 63-year-old man with a history of lung cancer underwent lobectomy of the right upper lobe and bronchoplasty. At the 2-month follow-up, bronchial stenosis due to a granuloma was observed. Endoscopic débridement and balloon dilation were performed. At 1 month after the dilation, atelectasis occurred owing to cicatricial stenosis. We repeated balloon dilation, but the patient suffered from cicatricial restenosis. After a failed stent placement, balloon dilation was then performed every 2 weeks under local anesthesia; the stenosis was resolved after performing dilation 7 times. Short-term repeated balloon dilation was effective in this case.


The structures and physicochemical properties of organic cofactors in biocatalysis.
Many crucial biochemical reactions in the cell require not only enzymes for catalysis but also organic cofactors or metal ions. Here, we analyse the physicochemical properties, chemical structures and functions of organic cofactors. Based on a thorough analysis of the literature complemented by our quantitative characterisation and classification, we found that most of these molecules are constructed from nucleotide and amino-acid-type building blocks, as well as some recurring cofactor-specific chemical scaffolds. We show that, as expected, organic cofactors are on average significantly more polar and slightly larger than other metabolites in the cell, yet they cover the full spectrum of physicochemical properties found in the metabolome. Furthermore, we have identified intrinsic groupings among the cofactors, based on their molecular properties, structures and functions, that represent a new way of considering cofactors. Although some classes of cofactors, as defined by their physicochemical properties, exhibit clear structural communalities, cofactors with similar structures can have diverse functional and physicochemical profiles. Finally, we show that the molecular functions of the cofactors not only may duplicate reactions performed by inorganic metal cofactors and amino acids, the cell's other catalytic tools, but also provide novel chemistries for catalysis.


Factor XIIIa generation assay: a tool for studying factor XIII function in plasma.
Triggering the extrinsic coagulation pathway in plasma and using a fluorogenic factor XIIIa (FXIIIa) substrate for continuously monitoring FXIIIa activity, an FXIIIa generation curve is obtained. The parameters area under the curve (AUC), time to peak (TTP), and concentration at peak (CP) were calculated. In dilutions of normal plasma in FXIII-deficient plasma, AUC and CP showed linear dose-response relationships, whereas TTP increased from 9.9 min for 25% FXIII to 11.6 min for 100% FXIII. Three FXIII-A preparations (rFXIII, rFXIII(V34L), and cellular FXIII [cFXIII]) showed a linear dose response for AUC and CP. The TTP increased slightly for rFXIII from 13.5 to 15.0 min, but surprisingly for cFXIII TTP increased concentration dependently from 13.5 to 28.7 min. Adding 5 μg/ml FXIII-B at a concentration of 1U of FXIII-A increased the AUC for rFXIII(V34L) and cFXIII by approximately 20% and accelerated TTP from 27.3 to 20.8 min for cFVIII, indicating a supportive function of FXIII-B in orientating cFXIII-A for thrombin cleavage. A commercial assay quantifying FXIII after complete activation in a restricted time window did not reveal differences in the cFXIII preparation with or without FXIII-B. The FXIIIa generation assay provides additional information about activation and function of FXIII. This advantage was underlined in experiments with an irreversible FXIIIa inhibitor.


The bromoporphyrins as promising anti-tumor photosensitizers in vitro.
The synthesis of ideal photosensitizers (PSs) is considered to be the most significant bottleneck in photodynamic therapy (PDT). To discover novel PSs with excellent photodynamic anti-tumor activities, a series of novel photosensitizers 5,15-diaryl-10,20-dibromoporphyrins (I1-6) were synthesized by a facile method. Compared with hematoporphyrin monomethyl ether (HMME) as the representative porphyrin-based photosensitizers, it is found that not only the longest absorption wavelength of all compounds was red-shifted to therapeutic window (660 nm) of photodynamic therapy, but also the singlet oxygen quantum yields were significantly increased. Furthermore, all compounds exhibited lower dark toxicity (except I2) and stronger phototoxicity (except I4) against Eca-109 tumor cells than HMME. Among them, I3 possessed the highest singlet oxygen quantum yield (ΦΔ = 0.205), the lower dark toxicity and the strongest phototoxicity (IC50 = 3.5 μM) in vitro. The findings indicated the compounds I3 had the potential to become anti-tumor agents for PDT.


Atrial fibrillation induced by testing magnet applied to VVI pacemaker.
The first known case of testing magnet-induced atrial fibrillation in a patient with a VVI pacemaker is reported. A macrore-entry mechanism is postulated, involving retrograde conduction from the ventricle through the AV node to the atrium following an asynchronous pacemaker stimulus.


Immunohistochemical expression of matrix metalloproteinases 1, 2, 7, 9, and 26 in the calcifying cystic odontogenic tumor.
The aim was to evaluate immunoexpression of matrix metalloproteinases (MMPs) 1, 2, 7, 9, and 26 in calcifying cystic odontogenic tumor (CCOT). Ten cases of CCOT were assessed by immunohistochemical expression of MMPs 1, 2, 7, 9, and 26 in the parenchyma and stroma. Metalloproteinase immunoexpressions and their distribution pattern were semiquantitatively scored. MMPs were expressed in the parenchyma and stroma in all cases of CCOT. Regarding the percentage of immunostained parenchymal cells, MMPs 1, 7, and 9 showed score 2 in 100% of cases. For MMP-2, there was a predominance of score 0 (90%), whereas for MMP-26 immunostaining was varied. The staining of these metalloproteinases, with the exception of MMP-2, suggests their contribution to tumor growth and expansion. The presence of these metalloproteinases in stromal cells reveals the active participation of these cells in the degradation of the extracellular matrix, contributing to the growth of the tumor studied.


Pulmonary resection using automatic stapling devices.
Between January 1980 and December 1986, 674 patients underwent pulmonary surgery at this institution under the supervision of one surgeon (RJD). Automatic stapling devices were used to close the bronchus in all but 12 patients. Malignant disease was the reason for 85% of resections. The operative mortality was 4.9% (3.2% in patients undergoing lobectomy and 8.3% in those undergoing pneumonectomy). The complication rate was 17.3%. Bronchopleural fistula (BPF) occurred in 11 patients, an incidence of 1.7%. The post-pneumonectomy incidence of BPF was 2.7% within 3 months of surgery and 4.5% overall. Stapled closure of one or more hilar vessels was employed in 153 patients. The role of staplers in pulmonary surgery with particular reference to the incidence of bronchopleural fistula is examined.


Electroconvulsive therapy can benefit from controlled hyperventilation using a laryngeal mask.
Hypocapnia through hyperventilation is a well-known procedure in electroconvulsive therapy (ECT) to enhance seizure activity. However, it has mostly been applied in an uncontrolled manner. Originally intended for a better management of the supraglottic airway, laryngeal masks are more suited to monitor levels of CO(2) during hyperventilation than face masks and thereby provide for the possibility of controlled hyperventilation (CHV). The impact of CHV was retrospectively studied in 114 consecutive patients; 65 of them had received ECT with CHV and 49 had received ECT with uncontrolled hyperventilation (UHV) directly prior to the time period when the laryneal mask was introduced to the ECT treatment procedure. The CO(2) level in the CHV group was aimed at 30 mmHg or below. CHV considerably enhanced the seizure activity leading to changes in clinically determined parameters of the treatment course: the necessity for increasing the electric charge, for re-stimulations (trend) and for bilateral stimulations was lower in the CHV group as compared to the UHV group. The improvement in the Global Assessment of Functioning Scores was not different in both groups. CHV was associated with a higher amount of prolonged seizures, with a reduced number of delirious symptoms after treatments and an attenuating effect on heart rate. Concluding, CHV can help to maintain the applied electric charge low without worsening the clinical outcome. Therefore, it is a helpful technical improvement. However, it should be used carefully with regard to prolonged seizures.


Stereocontrolled Formation of a [4.4]Heterospiro Ring System with Unexpected Inversion of Configuration at the Spirocenter.
Stereoselective construction of the 1,3-diazaspiro[4.4]nonane core skeleton of massadine and related dimeric pyrrole-imidazole alkaloids is a synthetic challenge. We describe herein the synthesis of all C13/14 diastereomers of this spiro molecule through controlled oxidation and epimerization of the C13 spirocenter under mild acidic conditions.


MRI safety, imaging artefacts, and grid distortion evaluated for FFP3 respiratory masks worn throughout the COVID-19 pandemic.
To determine which filtering face piece (FFP3) respirators worn throughout the COVID-19 pandemic are safe for magnetic resonance imaging (MRI). Three clinical MRI sequences were performed to assess imaging artefacts, grid distortion, and local heating for eight commercially available FFP3 respirators. All examinations were performed at Cardiff University Brain Research Imaging Centre using a 3 T Siemens Magnetom Prisma with a 64-channel head and neck coil. Each FFP3 mask was positioned on a custom-developed three-dimensional (3D) head phantom for testing. Five of the eight FFP3 masks contained ferromagnetic components and were regarded as "MRI unsafe". One mask was considered "MRI conditional" and only two masks were deemed "MRI safe" for both MRI staff and patients. Temperature strips positioned at the nasal bridge of the phantom did not exhibit local heating. A maximum grid distortion of 5 mm was seen in the anterior portion of the head of the ferromagnetic FFP3 masks. This study has demonstrated the importance of assessing respiratory FFP3 masks for use in and around MRI machines. Future research involving FFP3 masks can be conducted safely by following the procedures laid out in this study.


Molecular insights into the catalysis and regulation of mammalian NAD-dependent isocitrate dehydrogenases.
Eukaryotic NAD-dependent isocitrate dehydrogenases (NAD-IDHs) are mitochondria-localized enzymes which catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate using NAD as a cofactor. In mammals, NAD-IDHs (or IDH3) consist of three types of subunits (α, β, and γ), and exist as (α2βγ)2 heterooctamer. Mammalian NAD-IDHs are regulated allosterically and/or competitively by a diversity of metabolites including citrate, ADP, ATP, NADH, and NADPH, which are associated with cellular metabolite flux, energy demands, and redox status. Proper assembly of the component subunits is essential for the catalysis and regulation of the enzymes. Recently, crystal structures of human IDH3 have been solved in apo form and in complex with various ligands, revealing the molecular mechanisms for the assembly, catalysis, and regulation of the enzyme.


The effect of provider characteristics on case management activities.
The authors investigated the impact of provider characteristics on the performance of clinical case managers. Case managers in a large California county were interviewed using a structured instrument that assessed service linkage, assertive outreach, and family management. Findings indicate that assertive outreach was done more often by more experienced case managers, and less often by those with larger caseloads. Belief in the efficacy of an activity was associated with doing it much more frequently.


[CBO guidelines to prevent accidental falls in the elderly: how can it be used in the institutionalized elderly?].
Fall incidents occur frequently in the community dwelling elderly and even more in the institutionalised elderly. Fall-related research data indicate positive effects of a multifactorial intervention targeted on prevention of falls and fall-related injuries. In November 2004 the guideline "Prevention of fall incidents in the elderly" developed by The Dutch Institute for Healthcare Improvement (CBO) was published. This guideline pays attention to the risk factors for falling and the prevention of fall incidents in all settings. The highlights for nursing homes are: all nursing home patients are at risk; perform a fall risk assessment to direct fall preventive activities; together with specific fall prevention for the patient general fall prevention for the institute has to be undertaken; a multifactorial approach is indicated. In nursing homes it is possible to perform such approach multidisciplinary.


Aluminium incorporation in polar, semi- and non-polar AlGaN layers: a comparative study of x-ray diffraction and optical properties.
Growth of AlxGa1-xN layers (0 ≤ x ≤ 1) simultaneously on polar (0001), semipolar ([Formula: see text]3) and ([Formula: see text]), as well as nonpolar ([Formula: see text]) and ([Formula: see text]) AlN templates, which were grown on planar sapphire substrates, has been investigated by metal-organic vapour phase epitaxy. By taking into account anisotropic in-plane strain of semi- and non-polar layers, their aluminium incorporation has been determined by x-ray diffraction analysis. Optical emission energy of the layers was obtained from room-temperature photoluminescence spectra, and their effective bandgap energy was estimated from room-temperature pseudo-dielectric functions. Both x-ray diffraction and optical data consistently show that aluminium incorporation is comparable on the polar, semi- and non-polar planes.


Laser influence on the rate of degeneration of damaged nerves.
The sciatic nerves were sectioned and sutured back. The rate of degeneration at the point of suture was studied. Laser treatment increased the rate of degeneration of the damaged fibers.


In vitro comparison of antifungal effects of a coal tar gel and a ketoconazole gel on Malassezia furfur.
Malassezia furfur seems to be a major pathogenetic factor in seborrhoeic dermatitis, a frequent human skin disease. To estimate the antifungal properties of a coal tar gel (5 mg ml-1 coal tar) which is used in the treatment of seborrhoeic dermatitis of the scalp, we compared its effects on the in vitro growth of M. furfur with those of a ketoconazole gel (20 mg ml-1 ketoconazole). None of the gels was fungicidal within incubation times up to 20 min. During a single application, both gels remain on the skin for only 5 min. Fungicidal effects are consequently unlikely to play a substantial therapeutic role. Fungistatic effects were observed with both gels. In cultures inoculated with 1 x 10(3) cells ml-1, a 1:49 152 dilution of the ketoconazole gel and a 1:768 dilution of the coal tar gel still showed inhibitory effects. At inoculum densities of 1 x 10(5) ml-1, both gels were fungistatic only in dilutions of a maximum of 1:40. Our results suggest that under clinical treatment conditions the fungistatic activities of both preparations should be comparable.


A pharmacoproteomic landscape of organotypic intervention responses in Gram-negative sepsis.
Sepsis is the major cause of mortality across intensive care units globally, yet details of accompanying pathological molecular events remain unclear. This knowledge gap has resulted in ineffective biomarker development and suboptimal treatment regimens to prevent and manage organ dysfunction/damage. Here, we used pharmacoproteomics to score time-dependent treatment impact in a murine Escherichia coli sepsis model after administering beta-lactam antibiotic meropenem (Mem) and/or the immunomodulatory glucocorticoid methylprednisolone (Gcc). Three distinct proteome response patterns were identified, which depended on the underlying proteotype for each organ. Gcc enhanced some positive proteome responses of Mem, including superior reduction of the inflammatory response in kidneys and partial restoration of sepsis-induced metabolic dysfunction. Mem introduced sepsis-independent perturbations in the mitochondrial proteome that Gcc counteracted. We provide a strategy for the quantitative and organotypic assessment of treatment effects of candidate therapies in relationship to dosing, timing, and potential synergistic intervention combinations during sepsis.


Spontaneous tooth exfoliation, maxillary osteomyelitis and facial scarring following trigeminal herpes zoster infection.
A case of trigeminal herpes zoster (HZ) infection affecting the left maxillary and ophthalmic divisions of the fifth cranial nerve in an immuno-competent patient is presented. Extremely rare complications such as osteonecrosis, spontaneous tooth exfoliation, secondary osteomyelitis and facial scarring were observed. Sequestrectomy, aciclovir and erythromycin stearate were effectively used in managing the case.


Assessment of variability in nutritional quality of wild edible fruit of Monotheca buxifolia (Falc.) A. DC. Along the altitudinal gradient in Pakistan.
The fruit of Monotheca buxifolia is among the underutilized wild edible fruits that grows in Hindukush and Suleiman range mountains of Pakistan. Mountain communities consume this wild fruit as a food, medicine and it provides an important source of income. In this study, we aimed to investigate the total yield and the effect that altitude plays on its proximate composition and mineral contents as determined through phytochemical screening of this economically important wild fruit. Our results indicate a significant increase in the total fruit yield with increasing trunk diameter (R2 = 0.98), height (R2 = 0.95) and cover (R2 = 0.92). The proximate composition shows that the crude fat and carbohydrate contents of Monotheca fruit significantly varies (P < 0.05) along the altitudinal gradient. Similarly, ANOVA followed by post hoc Tukey HSD, further confirms the variation (P < 0.01) in moisture contents of the fruit. Dry matter ranged from 95.28 ± 4.64 to 108 ± 3.70 g kg- 1 of the fruit's edible portion, while protein contents varied between 17.16 % and 20.44 %. The fruits were found to be rich in minerals containing sizeable amounts of potassium, iron, phosphorus, sodium, nitrogen, magnesium, and copper. Significant difference was observed in the nitrogen (P < 0.01), potassium (P < 0.05) and sodium (P < 0.05) contents of the fruit along the altitudinal gradient. Similarly, tannins, flavonoids, saponins, reducing sugars, terpenoids, anthraquinones, and cardiac glycosides, were the most prominent chemicals found in Monotheca fruit. It was concluded that Monotheca fruit is a good source of carbohydrates, proteins, macro and micro-nutrients which fluctuated along the altitudinal gradient.


Role of nanotechnology in agriculture with special reference to management of insect pests.
Nanotechnology is a promising field of interdisciplinary research. It opens up a wide array of opportunities in various fields like medicine, pharmaceuticals, electronics and agriculture. The potential uses and benefits of nanotechnology are enormous. These include insect pests management through the formulations of nanomaterials-based pesticides and insecticides, enhancement of agricultural productivity using bio-conjugated nanoparticles (encapsulation) for slow release of nutrients and water, nanoparticle-mediated gene or DNA transfer in plants for the development of insect pest-resistant varieties and use of nanomaterials for preparation of different kind of biosensors, which would be useful in remote sensing devices required for precision farming. Traditional strategies like integrated pest management used in agriculture are insufficient, and application of chemical pesticides like DDT have adverse effects on animals and human beings apart from the decline in soil fertility. Therefore, nanotechnology would provide green and efficient alternatives for the management of insect pests in agriculture without harming the nature. This review is focused on traditional strategies used for the management of insect pests, limitations of use of chemical pesticides and potential of nanomaterials in insect pest management as modern approaches of nanotechnology.


8-Azaguanine resistant African green monkey kidney cell mutants (Vero 153): isolation and characterization.
A clone of Vero cells resistant to up to 20 micrograms/ml 8-azaguanine was isolated. This clone (designated Vero 153) has a doubling rate of approximately 24 h and a maximum cell density of 10,000/mm2. Deficiency of the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT) in Vero 153 was demonstrated by methods of radiochromatography. Vero 153 is susceptible to hypoxanthine-thymidine-aminopterin (HAT) medium and its resistance to 8-azaguanine seems to be nonreversible. Like parental cells, Vero 153 was also incapable of interferon production when challenged with Newcastle disease virus (NDV) or poly(inosinic acid) . poly(cytidylic acid) (poly I:C). Similar chromosome complements (majority range 56 to 57) and band patterns were observed in cells harvested at Passages 10, 20, and 50. The potential use of Vero 153 for somatic cell hybridization for purposes of gene mapping, virus rescue, and the control of interferon production is discussed.


A pocket full of knowing--enhancing nursing practice with handheld computers.
PERIOPERATIVE NURSES are using high-tech, pocket-sized, handheld computers to perform a variety of functions and enhance nursing practice. THIS ARTICLE GIVES an introduction to handheld technology and provides feature and cost comparisons. NURSES CAN USE built-in programs to keep procedure notes, pertinent telephone numbers, and a calendar. Optional reference programs of interest to health care workers number in the hundreds.


Computed tomography as a diagnostic aid in diabetic and other problem feet.
Determining whether osteomyelitis is present in patients with foot infections represents a significant diagnostic challenge. As bone uptake with nuclide scans can be affected by soft tissue infection, we performed computed tomography (CT) on seven patients to see if marrow or bone abnormalities could be seen and used to predict the presence or absence of osteomyelitis. The CT scans correctly predicted the presence or absence of osteomyelitis in all seven patients. Four patients had osteomyelitis and three patients did not. Nuclide bone scans had one false-positive and one false-negative result. In this small series, CT proved helpful in evaluating foot problems.


Fatigue analysis of restored teeth longitudinally cracked under cyclic loading.
To investigate the fatigue behavior of restored teeth, in particular the mechanisms of longitudinal dentinal cracking under cyclic mechanical loading, using finite element analysis (FEA) and the stress-life (S-N) approach. Ten root-filled premolars restored with resin composites were subjected to step-stress cyclic loading to produce longitudinal cracks. Fracture loads and number of cycles completed at each load level were recorded. FEA was used to predict the stress amplitude of each component under the global cyclic load. Both intact and debonded conditions were considered for the dentin-composite interface in the FEA. The predicted stress concentrations were compared with the fracture patterns to help elucidate the failure mechanisms. The S-N approach was further used to predict the lifetimes of the different components in the restored teeth. Cumulative fatigue damage was represented by the sum of the fractions of life spent under the different stress amplitudes. Longitudinal cracks were seen in ~50% of the samples with a mean fracture load of 770 ± 45 N and a mean number of cycles to failure of 32,297 ± 12,624. The longitudinal dentinal cracks seemed to start near the line angle of the cavity, and propagated longitudinally towards the root. The sum of fractions of life spent for the dentin-composite interface exceeded 1 after ~7000 cycles when that for dentin was much lower than 1, indicating that interfacial debonding would occur prior to dentin fracture. This was supported by micro-CT images showing widened interfacial space in the cracked samples. In the debonded tooth, FEA showed dentinal stress concentrations at the gingival wall of the cavity, which coincided with the longitudinal cracks found in the cyclic loading test. The sum of fractions of life spent for dentin was close to 1 at ~30,000 cycles, similar to the experimental value. Debonding of the dentin-composite interface may occur prior to longitudinal cracking of dentin in root-filled teeth under cyclic loading. The approximate time of occurrence for these events could be estimated using fatigue analysis with stresses provided by FEA. This methodology can therefore be used to evaluate the longevity of restoration designs for root-filled teeth.


Protein-cationic detergent interaction. Interaction of bovine serum albumin and other proteins with alkylpyridinium bromides studied by viscosity, gel filtration and spin-label methods.
Viscosity, gel filtration and spin-labelling methods have been used to study the influence of alkylpyridinium bromides on the conformation of bovine serum albumin and other proteins. Cationic detergents cause partial unfolding of the native protein molecules. The magnitude of these changes increases with increasing length of the detergent hydrocarbon chain. When cationic detergents are added to reduced and carboxymethylated bovine serum albumin the observed changes are opposite to those found in native protein.