[Not Available].
In one of his medical works--"Cogitationes et observationes de climate hungarico" published in 1739--the Hungarian physician J. G. H. Kramer describes the very unhealthy climate of Hungary and the diseases and high death rate it causes among the inhabitants, especially foreigners. The longevity of part of the population is to be ascribed to an inherited adaptation to the climate and to peculiar nutrition and habits. Serbs, Wallachs and Gypsies abstain from eating meat almost nine months of the year. They take daily cold baths in all seasons, and the Serbs even immerge their new-born babies into cold water in summer as well as in winter. As regards health, vigour and longevity the Hungarians cannot be compared to the Serbs although they live in higher and more salubrious regions. Dr. Kramer's recommendations to people living in Hungary on the best way to keep their good health, represent the diet of the inhabitants belonging to the Greek Orthodox creed who, out of the 12 ethnic groups forming then the population of Hungary, were apparently the best adapted to the climate of their native country.


Development and clinical evaluation of an amplified flow cytometric fluoroimmunoassay for Clostridium difficile toxin A.
A rapid (2 h) amplified flow cytometric fluoroimmunoassay (AFCF) for Clostridium difficile toxin A was developed and compared with the cytotoxin assay (CTA) and culture of the organism from stool specimens from patients with suspected C. difficile-associated gastrointestinal disease (CAD). For this assay polyclonal antitoxin A was attached to 10-microns diameter and monoclonal antitoxin A was attached to fluorescent 0.1 micron-diameter polystyrene microspheres. The microspheres and sample were reacted together as in a conventional double-antibody sandwich assay. However, laser flow cytometric measurement allowed the omission of separation and washing steps by gating on light scattered by the larger microspheres and measuring only the fluorescence associated with these particles. The amount of fluorescence from the attached 0.1 micron microspheres was dependent on the concentration of toxin A in the sample. The AFCF detected purified toxin A at levels of 1 pg/ml and was linear from 1 to 40 pg/ml. The AFCF was compared with the CTA and culture of C. difficile for clinical use by comparing results from 198 stool specimens from patients with suspected CAD. The AFCF was 85.7% sensitive and 95.8% specific relative to the CTA, and 85.2% sensitive and 98.3% specific compared to the culture assay. If the isolation of toxigenic C. difficile or the patients clinical course was considered indicative of CAD, the sensitivities of the AFCF, CTA, and culture assay were 77.4%, 67.7% and 96.8%, respectively. The AFCF demonstrated a specificity of 98.8%, while both CTA and culture had a specificity of 100%.(ABSTRACT TRUNCATED AT 250 WORDS)


Pharmacokinetic and pharmacodynamic properties of alinidine in man.
The elimination kinetics of alinidine and the changes in heart rate and blood pressure were determined in five health subjects following intravenous and oral administration of single doses of 40 mg alinidine. The plasma concentration after the intravenous injection declined at least biexponentially with time, with mean half-lives of 0.6 +/- 0.15 h and 3.9 +/- 0.28 h for the distribution and the elimination phase, respectively. The mean total clearance amounted to 40.3 +/- 8.9 L/h and the renal clearance to 33.6 +/- 12.3 L/h. The bioavailability following oral administration was nearly complete (0.92 +/- 0.06). Alinidine produced a modest bradycardia effect in healthy subjects. The maximal decrease in the heart rate was 19.2 +/- 7.7% (p less than 0.05) and 14.2 +/- 8.1% (p less than 0.05) following intravenous and oral administration, respectively. Time intervals in surface electrocardiogram (duration of the P- wave, PG time, QRS duration, and QTc) were not significantly altered by alinidine after both routes of administration. There was also a slight but consistent decrease in the systolic blood pressure (3-8%) after both routes of administration, whereas the diastolic blood pressure remained unchanged.


Transforming growth factor-beta and epidermal growth factor modulate basal and interleukin-6-induced amino acid uptake and acute phase protein synthesis in cultured rat hepatocytes.
Rat hepatocytes cultured for 2 days with interleukin-6 show increased synthesis of acute phase proteins and enhanced accumulation of 14C-labelled alpha-aminoisobutyric acid. Transforming growth factor-beta 1 (0.1-10 ng/ml) inhibits whereas epidermal growth factor (1-100 ng/ml) enhances both basal and interleukin-6-induced amino acid uptake by rat hepatocytes with only a slight alteration of acute phase protein synthesis.


Biventricular long axis function after repair of tetralogy of Fallot.
Right ventricular restrictive physiology is common after repair of tetralogy of Fallot and relates to exercise performance and symptomatic arrhythmias. In this study, we examined biventricular long axis function in an attempt to clarify further the mechanical substrate of this phenomenon. We studied prospectively 95 patients with tetralogy of Fallot (age range 1-44.3 years) at a median of 4.3 years after repair with Doppler and M-mode echocardiography. Pulmonary arterial, tricuspid, and mitral Doppler spectrals and 2-D guided M-mode recordings of ventricular minor and long axes were obtained with simultaneous phonocardiogram and respirometer recordings. Right ventricular restriction was defined by the presence of antegrade pulmonary arterial flow during atrial systole throughout the respiratory cycle. Restrictive right ventricular physiology was demonstrated in 36 (39%) [group 1] of the 92 patients in whom the data were analyzed. Left ventricular function (FS, isovolumic relaxation time and transmitral E wave deceleration time) was not different in the two groups (p < 0.1, p < 0.6, and p < 0.8, respectively). The presence of antegrade diastolic flow shortened the pulmonary regurgitation in the restrictive group (PR duration/square root of RR 10.7 +/- 2.1 vs 12.1 +/- 2.1, p < 0.01). There was delayed onset of shortening (97.4 +/- 24 vs 88.8 +/- 24 ms, p = 0.01), and the amplitude of right atrioventricular ring excursion, corrected for body surface area, was significantly lower during atrial systole in the restrictive group (0.43 +/- 0.15 vs 0.54 +/- 0.2 cm/m2, p < 0.01). There was also a tendency toward a smaller ratio of right to left total atrioventricular ring excursion in the same group (1.14 +/- 0.19 vs 1.22 +/- 0.23, p = 0.1). Impaired long axis function in patients with restrictive right ventricular physiology following repair of tetralogy of Fallot is associated with abnormal diastolic filling and may contribute to the long-term cardioprotective effect of restrictive physiology by limiting the degree of right ventricular dilatation.


Synthesis, biological evaluation, and enzyme docking simulations of 1,5-diarylpyrrole-3-alkoxyethyl ethers as selective cyclooxygenase-2 inhibitors endowed with anti-inflammatory and antinociceptive activity.
A series of substituted 1,5-diarylpyrrole-3-alkoxyethyl ethers (6, 7, and 8) has been synthesized with the aim to assess if in the previously reported 1,5-diarylpyrrole derivatives (5) the replacement of the acetic ester moiety with an alkoxyethyl group still led to new, highly selective and potent COX-2 inhibitors. In the in vitro cell culture assay, all the compounds proved to be potent and selective COX-2 inhibitors. In the human whole blood (HWB) assay, compound 8a had a comparable COX-2 selectivity to valdecoxib, while it was more selective than celecoxib but less selective than rofecoxib. The potential anti-inflammatory and antinociceptive activities of compounds 7a, 8a, and 8d were evaluated in vivo, where they showed a very good activity against both carrageenan-induced hyperalgesia and edema in the rat paw test. In the abdominal constriction test compound 7a, 8a, and 8d were able to reduce the number of writhes in a statistically significant manner. Furthermore, the affinity data of these compounds have been rationalized through enzyme docking simulations in terms of interactions with a crystallographic model of the COX-2 binding site by means of the software package Autodock 3.0.5, GRID 21, and MacroModel 8.5 using the complex between COX-2 and SC-558 (1b), refined at a 3 A resolution (Brookhaven Protein Data Bank entry: 6cox ).


Menopausal hormone therapy in Germany. Results of three national surveys from 1997 to 2003.
To determine regional variations in the prevalence and applied therapy regimes of current menopausal hormone therapy (HT) in Germany. Three population-based surveys, analysing data of 45-74 years old women, were compared: The Study of Health in Pomerania (SHIP; 1123 participants; northeast Germany, October 1997-May 2001), Cooperative Health Research in the Augsburg Region Survey 2000 (KORA; 1253 participants; south Germany, October 1999-April 2001) and Heinz Nixdorf Recall Study (HNR; 2257 participants; west Germany, December 2000-August 2003). A standardized interview technique provided data on current medication. The age-standardized prevalence of HT was 17.0% (95% confidence interval (CI): 14.9-19.1) in SHIP, 25.9% (95% CI: 23.6-28.3) in KORA and 24.7% (95% CI: 22.9-26.4) in HNR. Mean average time of intake of HT was 5.1 (SHIP), 7.5 (KORA) and 10.1 years (HNR). The use of estrogen plus progestogen combinations was equally common in all three surveys with proportions of about 15%, the use of unopposed estrogen in KORA and HNR was twice as high as in SHIP. In all three surveys oral estradiol was taken most often. Transdermal estradiol was preferred by KORA women whereas conjugated estrogens were taken most frequently by HNR women. Compared to northeast Germany HT was more often applied in the south and west of Germany. HT as long-term therapy was more common in West than in East Germany. In each study region there was a specific pattern of used HT components.


p38 MAPK signaling and phosphorylations in the BRCT1 domain regulate XRCC1 recruitment to sites of DNA damage.
XRCC1 is a scaffold protein involved in base excision repair and single strand break repair. It is a phosphoprotein that contains more than 45 phosphorylation sites, however only a few of these have been characterized and connected to specific kinases and functions. Mitogen activated protein kinases (MAPK) are mediators of cellular stress responses, and here we demonstrate that p38 MAPK signaling is involved in phosphorylation of XRCC1 and regulation of recruitment to oxidative stress. Inhibition of p38 MAPK caused a marked pI shift of XRCC1 towards a less phosphorylated state. Inhibition of p38 also increased the immediate accumulation of XRCC1 at site of DNA damage in a poly(ADP)-ribose (PAR) dependent manner. These results suggest a link between PARylation, p38 signaling and XRCC1 recruitment to DNA damage. Additionally, we characterized two phosphorylation sites, T358 and T367, located within, or close to, the phosphate-binding pocket of XRCC1, which is important for interaction with PAR. Mutation of these sites impairs recruitment of XRCC1 to DNA damage and binding to PARP1/PAR. Collectively, our data suggest that phosphorylation of T358 and T367 and p38 signaling are important for proper regulation of XRCC1 recruitment to DNA damage and thereby avoidance of potential toxic and mutagenic BER-intermediates.


Pulsed Radiofrequency for Treating Trigeminal Neuralgia.
Trigeminal neuralgia is the most common cause of facial pain but can be challenging to treat. Some patients fail on medications, and while surgical procedures achieve short-term efficacy, they can be associated with numerous complications. We present a case series suggesting the efficacy and safety of using pulsed radiofrequency (PRF) through the transcoronoid approach to treat trigeminal neuralgia. This retrospective analysis included 8 cases with data collected from the electronic medical record. Outcomes were pain scores before and after the procedure as well as the percent improvement after the procedure (improvement in severity, frequency, and duration). Patients had an average age of 56.4 ± 13 years. All patients reported improvement after the procedure, and 3 patients reported that their improvement was ongoing at the time of follow-up. No complications were reported by any of our patients. PRF through the transcoronoid approach may be a safe and effective approach for treating trigeminal neuralgia in patients resistant to conservative management.


Recovery of 2,3-Butanediol from Fermentation Broth by Zeolitic Imidazolate Frameworks.
The efficient separation of the 2,3-butanediol (2,3-BDO) intermediate from fermentation broth is an important issue in the production of biofuels from biomass-derived intermediates. Two zeolitic imidazolate frameworks ZIF-8 and ZIF-71 were investigated for the adsorption of 2,3-butanediol (2,3-BDO) from fermentation broth via liquid breakthrough adsorption measurements. While both ZIF materials initially show high separation performance, ZIF-71 retains robust separation performance even after aging in ethanol for two years, whereas the capacity of ZIF-8 decreases significantly. The robustness and stability of ZIF-71 are further confirmed with cyclic fixed bed adsorption measurements. The uptake of 2,3-BDO on ZIF-71 reaches >100 g/kg with negligible uptakes of sugars, organic acids, and other alcohols present in the fermentation broth. Excellent selectivity toward 2,3-BDO over water is also achieved. The 2,3-BDO-loaded ZIF-71 can be regenerated efficiently with ethanol as desorbent. These findings indicate that ZIF-71 shows considerable promise as an adsorbent to recover and purify diols from fermentation broths.


Anterior Temporal Sulcus: A Reliable Intraoperative Landmark for Accurately Delineating the Superior Limit of Amygdala Resection during Anterior Temporal Lobectomy.
Reliable anatomical landmarks are essential to avoiding injuries to the optic tract, anterior choroidal artery and basal ganglia during anterior temporal lobectomy (ATL). We describe an anatomic landmark, specifically the anterior temporal sulcus (ATS), as a reliable method to define the anterior portion of the endorhinal sulcus and the superior limit of amygdala resection. A total of 25 consecutive patients undergoing ATL at Rush University Medical Center (RUMC) were identified, and their preoperative brain magnetic resonance imaging (MRI) studies were analyzed. All patients underwent successful ATL without any complication. There was no injury to the optic tract, anterior choroidal artery or basal ganglia using ATS as the landmark for the superior limit of amygdala resection. The ATS was clearly identifiable on coronal preoperative MRI in 48 out of 50 temporal lobes (96%). The ATS was present in all 25 left temporal lobes (100%); 2 of the 25 right temporal lobes had absent ATS (8%). Following the ATS posteriorly on coronal MRI, it led to the endorhinal sulcus and accurately predicted the superior extent of amygdala resection in all 25 patients (48 temporal lobes). The ATS is a reliable anatomical landmark that accurately delineates the superior border of the amygdala during ATL.


Pleiotropic role of PPARγ in intracerebral hemorrhage: an intricate system involving Nrf2, RXR, and NF-κB.
Intracerebral hemorrhage (ICH) is a subtype of stroke involving formation of hematoma within brain parenchyma, which accounts for 8-15% of all strokes in Western societies and 20-30% among Asian populations, and has a 1-year mortality rate >50%. The high mortality and severe morbidity make ICH a major public health problem. Only a few evidence-based targeted treatments are used for ICH management, and interventions focus primarily on supportive care and comorbidity prevention. Even in patients who survive the ictus, extravasated blood (including plasma components) and subsequent intrahematoma hemolytic products trigger a series of adverse events within the brain parenchyma, leading to secondary brain injury, edema and severe neurological deficits or death. Although the hematoma in humans gradually resolves within months, full restoration of neurological function can be slow and often incomplete, leaving survivors with devastating neurological deficits. During past years, peroxisome proliferator-activated receptor gamma (PPARγ) transcription factor and its agonists received recognition as important players in regulating not only glucose and lipid metabolism (which underlies its therapeutic effect in type 2 diabetes mellitus), and more recently, as an instrumental pleiotropic regulator of antiinflammation, antioxidative regulation, and phagocyte-mediated cleanup processes. PPARγ agonists have emerged as potential therapeutic target for stroke. The use of PPARγ as a therapeutic target appears to have particularly strong compatibility toward pathogenic components of ICH. In addition to its direct genomic effect, PPARγ may interact with transcription factor, NF-κB, which may underlie many aspects of the antiinflammatory effect of PPARγ. Furthermore, PPARγ appears to regulate expression of Nrf2, another transcription factor and master regulator of detoxification and antioxidative regulation. Finally, the synergistic costimulation of PPARγ and retinoid X receptor, RXR, may play an additional role in the therapeutic modulation of PPARγ function. In this article, we outline the main components of the role of PPARγ in ICH pathogenesis.


[Postoperative management after cesarean section--infusion therapy and role of intestinal stimulation with parasympathomimetic drugs and dexpanthenon].
In the last decade the incidence of cesarean section has raised worldwide to 15-30% of all deliveries. A standardized postoperative protocol can be applied to most cases and it should be easy to handle and at low costs. In the present randomized, prospective study 76 consecutive patients who hat a cesarean section were investigated. Two different infusion therapy protocols were compared and the role of prophylactic stimulation of peristalsis by parasympathometic drugs and by the pantothenic acid derivative dexpanthenon was evaluated. In group A patient (n = 36) were treated postoperatively with intravenous glucose 5% plus electrolytes and received routinely neostigmine and dexpanthenon, while patients in group B (n = 40) were treated with standardized commercially available solutions without intravenous stimulation of the bowel. Both groups were similar in terms of age, parity, gestational age, past medical history and previous abdominal surgery. The volume of urine and the serum electrolyte levels were similar in both groups postoperatively. The first evacuation of the bowel occurred in most cases on day 3 (A = 69.5%, B = 82.5% of the patients). 50% of the patients in group A complained of abdominal discomfort and pain postoperatively and needed some therapy, while in group B only 22.5% of the cases hat similar complaints. This difference was statistically significant (chi 2 Test: p < 0.02). The present data suggest that prophylactic postoperative stimulation of the peristalsis after cesarean section increases the incidence of abdominal discomfort significantly without influencing the bowel function. Standardized solutions can be used mostly for immediate intravenous fluid replacement and oral intake can be started after 2-6 hours.


[Determinants of the choice of part time employment and nurses' satisfaction: a multicentre descriptive study].
To describe the main determinants for the choice of part time employment in Italian nurses and its' impact on work satisfaction. The main factors were identified with a focus-group. A questionnaire with 26 items for the choice of part time and 24 for work satisfaction was then devised and administered to part time nurses (503) of 5 North Italian hospitals. Two-hundred fifty-five nurses/471 answered the questionnaire. The choice of part time was voluntary for the large majority of nurses (251, 98.4%) except for 4 (1.6%) that asked for it for health problems (personal or of the spouse). Part time nurses are more satisfied for the relationships with colleagues (average 3; SD 0.6), the opportunity to deal with responsibilities (2.9; SD 0.6) and to have free time (2.9; SD 0.6). CONCLUSIONS; Part time is a need for mothers. Part time nurses complain for lack of access to information on patients and lack of involvement in ward projects and planned changes, possibly to be considered signals of isolation.


[Effects of chlorides on Cd transformation in a simulated grate incinerator during sludge incineration process ].
The effects of organic chloride-PVC and inorganic chloride-NaCl on Cd partitioning during sludge incineration with adding Cd(CH3COO)2 . 2H2O to the real sludge were investigated using a simulated tubular incineration furnace. And transformation and distribution of Cd were studied in different sludge incineration operation conditions. The results indicated that the partitioning of Cd tended to be enhanced in the fly ash and fule gas as the chloride content increasing. The migration and transformation of Cd-added sludge affected by different chloride were not obvious with the increasing of chloride content. With increasing temperature, organic chloride (PVC) and inorganic chloride (NaC1) can reduce the Cd distribution in the bottom ash. However, the effect of chlorides, the initial concentration and incineration time on Cd emissions had no significant differences. Using SEM-EDS and XRD technique, different Cd compounds including CdCl2, Na2CdCl4, K2CdCl6, K2CdSiO4 and NaCdO2 were formed in the bottom ash and fly ash after adding NaCl to the sludge. In contrast, after adding PVC to the sludge, the Na2CdCl4 and CdCl2 were the main forms of Cd compounds, at the same time, K4CdCI6 and K6CdO4 were also formed. The two different mechanisms of chlorides effects on Cd partitioning were affected by the products of Cd compound types and forms.


Dietary hexachlorocyclohexane induced changes in blood and liver lipids in albino mice.
Dietary intake of technical hexachlorocyclohexane (HCH) by albino mice for 2 weeks (at 400 and 800 ppm) resulted in hyperlipemia. Significant increase in triglycerides, phospholipids and cholesterol fractions of blood was observed in these animals. Dietary intake of gamma-isomer of HCH for 2 weeks (at 200 ppm) did not have any effect on blood lipid profile, but at 400 ppm level produced higher contents of phospholipids and cholesterol. The hepatomegaly produced by dietary technical HCH or gamma-HCH was not accompanied by fatty metamorphosis of liver. Hypertriglyceridemia caused by HCH was accompanied by lower triglyceride levels in liver, suggesting a possible higher rate of secretion from liver.


Should it be legal to assist suicide?
This paper argues that because it is a matter of dispute whether to assist suicide is ever morally right, the question whether assisted suicide should be legal should be decided independently of the moral issue and with reference to whether to assist suicide is genuinely to carry out the wishes of the person requesting it. It is then argued that it is possible to devise a set of criteria, based on those used in the Netherlands with regard to euthanasia, which would allow assisted suicide when the request is reasonable and genuine, but keep it illegal under other circumstances. It is further argued that there is no evidence that legalizing assisted suicide will lead us down the slippery slope to involuntary euthanasia. Finally, the question is raised to whether these assisted suicides should be legalized or, as at the moment in the UK, simply not prosecuted, but, as is about to happen, with the criteria for non-prosecution made explicit. It is suggested that, although it is in some ways both irrational and unjust, non-prosecution is politically easier to achieve and also more cautious as a first move.


Improving measurement accuracy by optimum data acquisition for Nd:YAG Thomson scattering system.
A new high speed Nd:YAG Thomson scattering AD Convertor (HYADC) that can directly convert the detected scattered light signal into a digital signal is under development. The HYADC is expected to improve a signal to noise ratio of the Nd:YAG Thomson scattering measurement. The data storage of the HYADC which is required for the direct conversion of whole plasma discharge is drastically reduced by a ring buffer memory and a stop trigger system. Data transfer of the HYADC is performed by the SiTCP. The HYADC is easily expandable to a multi-channel system by the distributed data processing, and is very compact and easy to implement as a built-in system of the polychromators.


Angular momentum dependent friction slows down rotational relaxation under nonequilibrium conditions.
It has recently been shown that relaxation of the rotational energy of hot nonequilibrium photofragments (i) slows down significantly with the increase of their initial rotational temperature and (ii) differs dramatically from the relaxation of the equilibrium rotational energy correlation function, manifesting thereby the breakdown of the linear response description [A. C. Moskun et al., Science 311, 1907 (2006)]. We demonstrate that this phenomenon may be caused by the angular momentum dependence of rotational friction. We have developed the generalized Fokker-Planck equation whose rotational friction depends upon angular momentum algebraically. The calculated rotational correlation functions correspond well to their counterparts obtained via molecular dynamics simulations in a broad range of initial nonequilibrium conditions. It is suggested that the angular momentum dependence of friction should be taken into account while describing rotational relaxation far from equilibrium.


Biological and technological variability of three anaerobic ergometer tests.
To assess the relative biological and technological variability of anaerobic testing, 27 male subjects performed either 30- or 60-s sprint bouts on a hydraulically braked Fitron ergometer or timed rides to exhaustion at 125% VO2max on an electrically braked Collins ergometer. Each subject performed four trials within a 4-week period, with blood drawn 10 min post-exercise for lactate determination. Total variability was estimated from the mean coefficient of variation (CV = SD/means X 100%) for each variable. There were no significant differences across the four trials of each test for any of the variables measured (mean power or ride time, peak torque, fatiguability, or blood lactate). There were also no significant differences in test variabilities. The mean CV of performance were 5.4%, 5.4%, and 5.3% for the 30-s Fitron, 60-s Fitron, and exhaustive tests, respectively. The magnitude of this variability is nearly identical to that reported for tests of aerobic fitness. Only 10%-30% of the variability was of technological origin. This variability must be considered in the interpretation of experiments utilizing anaerobic performance tests.


Panoramic zonography in radiographing the carpus.
The panoramic radiography technique enables the visualization of different image layers. In the search for a method for improving the radiological fracture diagnosis of the carpal bones the suitability of this technique for visualization of the carpal bones was tested. For panoramic zonography, Zonarc (Palomex, Finland) and its programme with cylindrical image layer with 85 mm radius was used. The present study showed that panoramic technique is suitable for discerning the carpal bones but not for demonstrating their skeletal details.


Fecal shedding of Helicobacter spp. by co-housed Australian sea lions (Neophoca cinerea) and Australian fur seals (Arctocephalus pusillus doriferus).
With the emergence of Helicobacter species as agents of gastrointestinal disease within a broad range of animal hosts, there is growing awareness of the need to identify such species and the potential role(s) they play within the intestine. Of interest in this study are captive seals and sea lions, where close proximity to one another may enhance the transmission of pathogens, in particular Helicobacter. The feces of several captive Australian sea lions and Australian fur seals were assessed for the occurrence of Helicobacter over 31 days. The presence of Helicobacter, detected by the polymerase chain reaction (PCR) varied over time and at times could not be detected. Helicobacter species were detected in five of the six animals examined of which two species were identified. This is the first report of Helicobacter species in captive seals and demonstrates the diversity and potential role(s) they may play in the gut of these animals.


Postoperative pain following outpatient pediatric urologic surgery: a comparison of anesthetic techniques.
To evaluate and compare the efficacy of caudal and local nerve blocks in preventing pain following outpatient pediatric urologic surgery. Seventy-seven boys undergoing outpatient urologic surgery were randomized into one of three groups: general anesthesia alone, general anesthesia and caudal nerve block, or general anesthesia and local nerve block. Pain scores, frequency of medication, and total dosage of medication were recorded in the immediate postoperative period. Long-term pain and discomfort were measured using a 24-hour and 1-week questionnaire. The caudal and local groups had lower pain scores and significantly lower medication requirements than the control group in the short-term postoperative period. The caudal group had lower pain scores than the local group in all categories; however, the only significant difference was at 24 hours postoperatively. At 1 week postoperatively, the only difference among the three groups was a lower pain score in the caudal group compared with the control group. This study demonstrates that for outpatient pediatric urologic procedures, both caudal and local nerve blocks significantly reduce pain and medication given in the immediate postoperative period and indicates that caudal block may decrease pain for up to 1 week following surgery.


Using computational fluid dynamics software to estimate circulation time distributions in bioreactors.
Nonideal mixing in many fermentation processes can lead to concentration gradients in nutrients, oxygen, and pH, among others. These gradients are likely to influence cellular behavior, growth, or yield of the fermentation process. Frequency of exposure to these gradients can be defined by the circulation time distribution (CTD). There are few examples of CTDs in the literature, and experimental determination of CTD is at best a challenging task. The goal in this study was to determine whether computational fluid dynamics (CFD) software (FLUENT 4 and MixSim) could be used to characterize the CTD in a single-impeller mixing tank. To accomplish this, CFD software was used to simulate flow fields in three different mixing tanks by meshing the tanks with a grid of elements and solving the Navier-Stokes equations using the kappa-epsilon turbulence model. Tracer particles were released from a reference zone within the simulated flow fields, particle trajectories were simulated for 30 s, and the time taken for these tracer particles to return to the reference zone was calculated. CTDs determined by experimental measurement, which showed distinct features (log-normal, bimodal, and unimodal), were compared with CTDs determined using CFD simulation. Reproducing the signal processing procedures used in each of the experiments, CFD simulations captured the characteristic features of the experimentally measured CTDs. The CFD data suggests new signal processing procedures that predict unimodal CTDs for all three tanks.


Transforming growth factor-beta inhibits telomerase through SMAD3 and E2F transcription factors.
Cancer arises from multiple genetic changes within the cell, among which constitutive telomerase activity and attainment of immortality are central. Expression of hTERT, the protein component of telomerase, is increased in most cancer cells. Transforming growth factor-beta (TGFbeta), a potent tumor suppressor, has been reported to regulate hTERT expression. We found that TGFbeta represses hTERT expression in normal and cancer cells and that this effect is mediated through Smad3 but also requires Erk1/2, p38 kinase and histone deacetylase activity. Furthermore, we identified four critical E2F transcription factor binding sites within the hTERT gene promoter that confer the TGFbeta response. Finally, using the E2F-1 knockout model, we showed that loss of E2F-1 abolishes TGFbeta inhibition of telomerase expression. These findings highlight the prominent role of TGFbeta in regulating telomerase expression and identify Smad3 and E2F-1 as critical mediators of TGFbeta effects in both normal and cancer cells.


Dorfman-Chanarin syndrome: a case with hyperlipidemia.
Dorfman-Chanarin syndrome is a rare, autosomal recessive disorder characterized by congenital ichthyosis and presence of intracellular lipid droplets in most tissues. Here, we present a patient from Turkey, who is the fourth Turkish case in the literature with this syndrome, and we review the previous reported cases. He was also the second case reported with hyperlipidemia.


Intra-operative imaging in trauma surgery.
The reconstruction of anatomical joint surfaces, limb alignment and rotational orientation are crucial in the treatment of fractures in terms of preservation of function and range of motion. To assess reduction and implant position intra-operatively, mobile C-arms are mandatory to immediately and continuously control these parameters.Usually, these devices are operated by OR staff or radiology technicians and assessed by the surgeon who is performing the procedure. Moreover, due to special objectives in the intra-operative setting, the situation cannot be compared with standard radiological image acquisition. Thus, surgeons need to be trained and educated to ensure correct technical conduct and interpretation of radiographs.It is essential to know the standard views of the joints and long bones and how to position the patient and C-arm in order to acquire these views. Additionally, the operating field must remain sterile, and the radiation exposure of the patient and staff must be kept as low as possible.In some situations, especially when reconstructing complex joint fractures or spinal injuries, complete evaluation of critical aspects of the surgical results is limited in two-dimensional views and fluoroscopy. Intra-operative three-dimensional imaging using special C-arms offers a valuable opportunity to improve intra-operative assessment and thus patient outcome.In this article, common fracture situations in trauma surgery as well as special circumstances that the surgeon may encounter are addressed. Cite this article: EFORT Open Rev 2018;3:541-549. DOI: 10.1302/2058-5241.3.170074.


Intermediary metabolism of fast-growth tumor cells.
Tumor cells show several modifications in their metabolism in comparison with normal cells. In particular, tumor cells show an accelerated glycolysis and a low O2 dependence, which are metabolic modifications involved in the resistance of many tumor cell lines to radiation. Thus, a strategy to enhance the radiosensitivity could be the transformation of the glycolytic metabolism of tumor cells into an oxidative type of metabolism, i.e., to induce the ATP supply to depend solely on oxidative phosphorylation. Therefore, this review emphasizes the relevance of oxidative phosphorylation on tumor cells regarding (a) its contribution to ATP supply for cell duplication during the proliferative phase, and (b) the possible therapeutic implications of having oxidative rather than glycolytic tumor cells.


Impact of Early versus Late Initiation of Renal Replacement Therapy in Patients with Cardiac Surgery-Associated Acute Kidney Injury: Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials.
Previous studies have examined the effect of the initiation time of renal replacement therapy (RRT) in patients with cardiac surgery-associated acute kidney injury (CSA-AKI), but the findings remain controversial. The aim of this meta-analysis was to systematically and quantitatively compare the impact of early versus late initiation of RRT on the outcome of patients with CSA-AKI. Four databases (PubMed, the Cochrane Library, ISI Web of Knowledge, and Embase) were systematically searched from inception to June 2018 for randomized clinical trials (RCTs). Two investigators independently performed the literature search, study selection, data extraction, and quality evaluation. Meta-analysis and trial sequential analysis (TSA) were used to examine the impact of RRT initiation time on all-cause mortality (primary outcome). The Grading of Recommendations Assessment Development and Evaluation (GRADE) was used to evaluate the level of evidence. We identified 4 RCTs with 355 patients that were eligible for inclusion. Pooled analyses indicated no difference in mortality for patients receiving early and late initiation of RRT (relative risk [RR] = 0.61, 95% confidence interval [CI] = 0.33 to 1.12). However, the results were not confirmed by TSA. Similarly, early RRT did not reduce the length of stay (LOS) in the intensive care unit (ICU) (mean difference [MD] = -1.04; 95% CI = -3.34 to 1.27) or the LOS in the hospital (MD = -1.57; 95% CI = -4.62 to 1.48). Analysis using GRADE indicated the certainty of the body of evidence was very low for a benefit from early initiation of RRT. Early initiation of RRT had no beneficial impacts on outcomes in patients with CSA-AKI. Future larger and more adequately powered prospective RCTs are needed to verify the benefit of reduced mortality associated with early initiation of RRT. This trial is registered with PROSPERO registration number CRD42018084465, registered on 11 February 2018.


Alternating Hemiplegia and Epilepsia Partialis Continua: A new phenotype for a novel compound TBC1D24 mutation.
Mutations in the TBC1D24 gene (MIM 613577) cause familial infantile myoclonic epilepsy (FIME; 605021) and early infantile epileptic encephalopathy-16 (EIEE16; 615338), both inherited with an autosomal recessive trait. The TBC1D24 gene encodes a member of the TBC family domain proteins, involved in cell signaling and oxidative stress resistance. We studied, by a Next Generation Sequencing (NGS) target re-sequencing gene approach, the DNA of a 5 year-old girl, affected by recurrent attacks of Alternating Hemiplegia (AH) and by recurrent episodes of Epilepsia Partialis Continua (EPC). The NGS study showed the presence of two different heterozygous, probably pathogenic variants in the TBC1D24 gene, inherited in trans from her parents: the c.116C>T (p.Ala39Val) and the c.457G>A (p.Glu153Lys). This study describes for the first time the association between TBC1D24 variants and AH expanding the phenotypic spectrum of TBC1D24-related diseases and suggesting that TBC1D24 molecular analysis should be considered in the diagnostic work up of AH patients. An additional peculiar feature is the association of AH and EPC.


Lateral Two-Dimensional Material Heterojunction Photodetectors with Ultrahigh Speed and Detectivity.
Lateral heterojunctions in two-dimensional (2D) materials have demonstrated potential for high-performance sensors because of the unique electrostatic conditions at the interface. The increased complexity of producing such structures, however, has prevented their widespread use. We here demonstrate the simple and scalable fabrication of heterojunctions by a one-step synthesis process that yields photodetectors with superior device performance. Catalytic conversion of a solid precursor at optimized conditions was found to produce lateral nanostructured junctions between graphene domains and 3 nm thin amorphous carbon films. Carrier transport in these heterojunctions was found to proceed by minimizing the path through the amorphous carbon barriers, which results in a self-selective Schottky emission process with high uniformity and low emission barriers. We demonstrate the potential of thus produced heterojunctions by realizing a photodetector that combines an ultrahigh detectivity of 1013 Jones with microsecond response time, which represents the highest performance of 2D material heterojunction devices. These attractive features are retained even for millimeter-scale devices, and the demonstrated ability to produce transparent, patterned, and flexible sensors extends lateral heterojunction sensors toward wearable and large-scale electronics.


Necrotising adenometaplasia (sialometaplasia) of the nasopharynx.
Necrotising sialometaplasia of the nasopharynx with nasal extension in a 43 year old man, with no preceding history of trauma, is reported. Some unusual histological features are described.


Clinical Features, Dermoscopic Patterns, and Histological Diagnostic Model for Melanocytic Tumors of Uncertain Malignant Potential (MELTUMP).
Cutaneous melanocytic lesions with atypical histological features can be difficult to categorize as benign or malignant. In the diagnosis of melanocytic lesions, the melanocytic tumor of uncertain malignant potential (MELTUMP) category has been widely used. Although one may favor a benign or malignant interpretation, a definitive diagnosis is not always possible, and long term clinical follow-up remains the only true evidence of biological behavior. We report 14 cases of MELTUMP with expert second opinion. Clinical pictures were available in 8 cases; dermoscopy was available in 5 cases. Accurate guidelines are delineated in the formulation of the diagnosis. We think that the histological diagnosis should be accompanied by a note in which the pathologist describes the histological pattern that has generated diagnostic uncertainty. Since the MELTUMP term does not exclude the malignant nature of the lesion, all microstaging attributes for melanoma should be added. Moreover, superficial atypical melanocytic proliferation of uncertain significance (SAMPUS) and MELTUMP categories should be included in the WHO classification of melanocytic tumors of the skin. The role of sentinel lymph node biopsy in MELTUMP has not yet been established. Recent studies have looked at concurrent tumor deposits in lymph nodes of MELTUMP, mostly of atypical Spitzoid lesions, and shown that these lesions rarely progress to overt malignancy. In our study, sentinel node metastasis was found in only one case. The follow-up period of this case and of the others has shown that the clinical outcome of MELTUMP tends to be favorable.


Determination of cholinesterase activity in brain and blood samples using a plate reader.
A rapid method is described for the quantitative determination of cholinesterase activity in large batches of blood and brain samples. The technique is an adaptation of the Ellman procedure for a 96-well microtiter plate reader. Ten samples can be analyzed simultaneously in 5 min, with all calculations, including statistical analysis, done automatically. The method detection limit is 0.1 microM/mL/min for blood and 0.1 microM/g/min for brain samples. The procedure has been applied to the routine analyses of samples presented to the veterinary diagnostic laboratory. Method performance, quality control, and normal ranges of cholinesterase activity in livestock and other animals are described.


Pathogen Decay during Managed Aquifer Recharge at Four Sites with Different Geochemical Characteristics and Recharge Water Sources.
Recycling of stormwater water and treated effluent via managed aquifer recharge (MAR) has often been hampered because of perceptions of low microbiological quality of recovered water and associated health risks. The goal of this study was to assess the removal of selected pathogens in four large-scale MAR schemes and to determine the influence of aquifer characteristics, geochemistry, and type of recharge water on the pathogen survival times. Bacterial pathogens tested in this study had the shortest one log removal time (, <3 d), followed by oocysts (, <120 d), with enteric viruses having the biggest variability in removal times (, 18 to >200 d). Human adenovirus and rotavirus were relatively persistent under anaerobic conditions (, >200 d). Human adenovirus survived longer than all the other enteric virus tested in the study and hence could be used as a conservative indicator for virus removal in groundwater during MAR. The results suggest that site-specific subsurface conditions such as groundwater chemistry can have considerable influence on the decay rates of enteric pathogens and that viruses are likely to be the critical pathogens from a public health perspective.


TDM-based imipramine treatment in neuropathic pain.
Tricyclic antidepressants (TCA) are the best-documented treatment of neuropathic pain. TCAs have a pronounced interindividual pharmacokinetic variability and a narrow therapeutic index. The aim of this study was to characterize the plasma concentration-effect relationship of imipramine in neuropathic pain and to determine the usefulness of therapeutic drug monitoring (TDM) of TCA treatment in a population with noncancer chronic pain. To do this, 83 patients with chronic noncancer neuropathic pain were included. Information on previous use of TCA was collected, and patients were tested for the presence of hyperalgesia. Pain intensity and pain relief were recorded, and the Short Form McGill Pain Questionnaire and Major Depression Inventory were completed before and during a TDM-based imipramine treatment. Imipramine dose was increased in steps of 25 mg/d every second week, and blood samples were taken at every dose. Endpoints were best possible pain relief, unacceptable side effects, or insufficient pain relief despite plasma drug level > 500 nmol/L. Dose range used was 10-300 mg/d. The study showed that imipramine 75 mg/d caused a 36-fold interindividual variation in steady-state plasma drug concentrations. In 46 responders (global pain relief > 25%) the plasma drug concentration at which an individual maximal analgesic effect was obtained ranged from 50 to 1400 nmol/L, but for the majority it was below 400 nmol/L. The concentration-effect relationship was similar for patients with central versus peripheral neuropathic pain and independent of the presence of hyperalgesia. Previous treatment failure with non-TDM TCA treatment was not a predictor of poor response to TDM-based treatment. In conclusion, there is a pronounced interindividual variability in concentration-effect relationship for imipramine treatment in neuropathic pain, but the majority of patients obtain a maximal analgesic effect at drug levels below 400 nmol/L. The concentration-effect relationship is similar for patients with central and peripheral neuropathic pain. Further studies are needed to document if TDM improves pain relief; however, TDM reduces the risk for toxicity.


Crossover clinical trial of benapryzine and trihexyphenidyl in Parkinsonian patients.
A crossover clinical trial of benapryzine and trihexyphenidyl in ten parkinsonian patients during a four-month study is described. The improvement from initial disability ranged from 29.5 to 64.4 per cent for benapryzine and from 27.2 to 64.9 per cent for trihexyphenidyl. The effect of benapryzine and trihexyphenidyl on most parkinsonian symptoms did not differ significantly. Patients taking benapryzine had significantly fewer of the common side effects of trihexyphenidyl but more sialorrhea. It is uncertain whether benapryzine is superior to trihexylphenidyl in the treatment of Parkinson's disease.


Chronic Stimulation of Renin Cells Leads to Vascular Pathology.
Experimental or spontaneous genomic mutations of the renin-angiotensin system or its pharmacological inhibition in early life leads to renal abnormalities, including poorly developed renal medulla, papillary atrophy, hydronephrosis, inability to concentrate the urine, polyuria, polydipsia, renal failure, and anemia. At the core of such complex phenotype is the presence of unique vascular abnormalities: the renal arterioles do not branch or elongate properly and they have disorganized, concentric hypertrophy. This lesion has been puzzling because it is often found in hypertensive individuals whereas mutant or pharmacologically inhibited animals are hypotensive. Remarkably, when renin cells are ablated with diphtheria toxin, the vascular hypertrophy does not occur, suggesting that renin cells per se may contribute to the vascular disease. To test this hypothesis, on a Ren1c-/- background, we generated mutant mice with reporter expression (Ren1c-/-;Ren1c-Cre;R26R.mTmG and Ren1c-/-;Ren1c-Cre;R26R.LacZ) to trace the fate of reninnull cells. To assess whether reninnull cells maintain their renin promoter active, we used Ren1c-/-;Ren1c-YFP mice that transcribe YFP (yellow fluorescent protein) directed by the renin promoter. We also followed the expression of Akr1b7 and miR-330-5p, markers of cells programmed for the renin phenotype. Contrary to what we expected, reninnull cells did not die or disappear. Instead, they survived, increased in number along the renal arterial tree, and maintained an active molecular memory of the myoepitheliod renin phenotype. Furthermore, null cells of the renin lineage occupied the walls of the arteries and arterioles in a chaotic, directionless pattern directly contributing to the concentric arterial hypertrophy.


Two dimensional modeling of elastic wave propagation in solids containing cracks with rough surfaces and friction - Part I: Theoretical background.
Our study aims at the creation of a numerical toolbox that describes wave propagation in samples containing internal contacts (e.g. cracks, delaminations, debondings, imperfect intergranular joints) of known geometry with postulated contact interaction laws including friction. The code consists of two entities: the contact model and the solid mechanics module. Part I of the paper concerns the modeling of internal contacts (called cracks for brevity), while part II is related to the integration of the developed contact model into a solid mechanics module that allows the description of wave propagation processes. The contact model is used to produce normal and tangential load-displacement relationships, which in turn are used by the solid mechanics module as boundary conditions at the internal contacts. Due to friction, the tangential reaction curve is hysteretic and memory-dependent. In addition, it depends on the normal reaction curve. An essential feature of the proposed contact model is that it takes into account the roughness of the contact faces. On one hand, accounting for roughness makes the contact model more complicated since it gives rise to a partial slip regime when some parts on the contact area experience slip and some do not. On the other hand, as we will show, the concept of contact surfaces covered by asperities receding under load makes it possible to formulate a consistent contact model that provides nonlinear load-displacement relationships for any value of the drive displacements and their histories. This is a strong advantage, since this way, the displacement-driven model allows for a simple explicit procedure of data exchange with the solid mechanics module, while more traditional flat-surface contacts driven by loads generate a complex iterative procedure. More specifically, the proposed contact model is based on the previously developed method of memory diagrams that allows one to automatically obtain memory-dependent solutions to frictional contact problems in the particular case of partial slip. Here we extend the solution onto cases of total sliding and contact loss which is possible while using the displacement-driven formulation. The method requires the knowledge of the normal contact response obtained in our case as a result of statistical consideration of roughness of contact faces.


Transcriptional regulation of APP by apoE: To boldly go where no isoform has gone before: ApoE, APP transcription and AD: Hypothesised mechanisms and existing knowledge gaps.
Alzheimer's disease (AD) is the most common form of dementia that gradually disrupts the brain network to impair memory, language and cognition. While the amyloid hypothesis remains the leading proposed mechanism to explain AD pathophysiology, anti-amyloid therapeutic strategies have yet to translate into useful therapies, suggesting that amyloid β-protein and its precursor, the amyloid precursor protein (APP) are but a part of the disease cascade. Further, risk of AD can be modulated by a number of factors, the most impactful being the ɛ4 isoform of apolipoprotein E (apoE). A recent study reported a novel isoform-dependent transcriptional regulation of APP by apoE. These interesting new results add to the myriad of mechanisms that have been proposed to explain how apoE4 enhances AD risk, highlighting the complexities of not only apoE and AD pathophysiology, but also of disease itself. Also see the video abstract here: https://youtu.be/yd14MBdPkCY.


When the risks are high: psychological adjustment among melanoma survivors at high risk of developing new primary disease.
In this study we explored the psychosocial experiences of melanoma survivors at high risk of developing new primary disease. A total of 20 survivors (9 men, 11 women, mean age 57.6 years) completed a semistructured telephone interview, exploring melanoma-related beliefs and experiences, psychological adjustment to melanoma risk, and supportive care needs. Participants perceived melanoma as potentially terminal and reported persistent worries about the possibility of developing new or metastatic disease. Fear of developing a new melanoma endured for years after treatment completion and, for some, created a pervasive sense of uncertainty. Still, not a single participant sought formal emotional support to address his or her melanoma-related concerns. Belief in the benefits of early intervention, including self- and clinical skin examination, provided a sense of control and a recommended course of action in an otherwise uncontrollable situation. The expertise of the High Risk Clinic physicians was perceived as instrumental in creating a sense of reassurance.


An eye tracking system for monitoring face scanning patterns reveals the enhancing effect of oxytocin on eye contact in common marmosets.
Eye tracking systems are used to investigate eyes position and gaze patterns presumed as eye contact in humans. Eye contact is a useful biomarker of social communication and known to be deficient in patients with autism spectrum disorders (ASDs). Interestingly, the same eye tracking systems have been used to directly compare face scanning patterns in some non-human primates to those in human. Thus, eye tracking is expected to be a useful translational technique for investigating not only social attention and visual interest, but also the effects of psychiatric drugs, such as oxytocin, a neuropeptide that regulates social behavior. In this study, we report on a newly established method for eye tracking in common marmosets as unique New World primates that, like humans, use eye contact as a mean of communication. Our investigation was aimed at characterizing these primates face scanning patterns and evaluating the effects of oxytocin on their eye contact behavior. We found that normal common marmosets spend more time viewing the eyes region in common marmoset's picture than the mouth region or a scrambled picture. In oxytocin experiment, the change in eyes/face ratio was significantly greater in the oxytocin group than in the vehicle group. Moreover, oxytocin-induced increase in the change in eyes/face ratio was completely blocked by the oxytocin receptor antagonist L-368,899. These results indicate that eye tracking in common marmosets may be useful for evaluating drug candidates targeting psychiatric conditions, especially ASDs.


Uniform implantation of CNTs on total activated carbon surfaces: a smart engineering protocol for commercial supercapacitor applications.
The main obstacles to building better supercapacitors are still trade-offs between energy and power parameters. To promote commercial supercapacitor behaviors, proper optimization toward electrode configurations/architectures may be a feasible and effective way. We herein propose a smart and reliable electrode engineering protocol, by in situ implantation of carbon nanotubes (CNTs) on total activated carbon (AC) surfaces via a mild chemical vapor deposition process at ∼550 °C, using nickel nitrate hydroxide (NNH) thin films and waste ethanol solvents as the catalyst and carbon sources, respectively. The direct and conformal growth of NNH layers onto carbonaceous scaffold guarantees the later uniform implantation of long and high-quality CNTs on total AC outer surfaces. Such fluffy and entangled CNTs preserve ionic diffusion channels, well connect neighboring ACs and function as superhighways for electrons transfer, endowing electrodes with outstanding capacitive behaviors including large output capacitances of ∼230 F g-1 in 1 M Na2SO4 neutral solution and ∼502.5 F g-1 in 6 M KOH using Ni valence state variation, and very negligible capacity decay in long-term cycles. Furthermore, a full symmetric supercapacitor device of CNTs@ACs//CNTs@ACs has been constructed, capable of delivering both high specific energy and power densities (maximum values reaching up to ∼97.2 Wh kg-1 and ∼10.84 kW kg-1), which holds great potential in competing with current mainstream supercapacitors.


Binocular-disparity-dependent upper-lower hemifield anisotropy and left-right hemifield isotropy as revealed by dynamic random-dot stereograms.
Dynamic random-dot stereograms devoid of all monocular depth cues were used to measure the limits of temporal and spatial resolution in the center of the visual field. The temporal durations for detecting a small, briefly presented test square of different binocular disparity than the surround varied as a function of its location and binocular disparity. The test squares presented in the upper hemifield were detectable at consistently shorter durations than those presented in the lower hemifield for a surround disparity which was uncrossed relative to the fixation marker. For crossed surround disparity this preference reversed, resulting in a superiority of the lower hemifield. The anisotropy diminished for zero surround disparity. No such anisotropy was found when left and right visual hemifields were compared. It was also shown that this upper-lower temporal anisotropy (and left-right isotropy) is paralleled by a similar disparity-dependent upper-lower anistropy (and left-right isotropy) in spatial resolution. Introduction of monocular clues into the stereograms tended to eliminate the anisotropies. This implies that the anisotropies reflect the spatiotemporal properties and distribution of binocular disparity detectors in the human cortex and result in a tilted surface that pivots around the horizontal midline in the space of binocular depth perception.


[Left ventricular pressure-volume diagram determined by forward and backward formatting of radionuclide ventriculography and analog pressure data].
Pressure-volume (PV) loop is of great value for the assessment of left ventricular (LV) function, but its clinical application has been limited by methodological complexity. A new system was developed to make accurate loop with simplified procedure, and was applied to clinical and interventional study. The system constitutes of a mobile gamma camera, a poly-amplifier and a data processor (GMS-550U, Toshiba Medical) installed in cardiac catheterization labo for simultaneous raw data handling and successive analysis. Since LV time activity curve (TAC) obtained by usual ECG gating is not fully reliable for a entire cardiac cycle, radionuclide data acquired in list mode was formatted forward and backward from ECG trigger together with analog data of LV pressure, ECG and PCG. PV loops were drawn in 10 patients (OMI, AP, MR, HCM) and 5 normals before and after infusion of angiotensin-II (AII), and Emax and LV work (systolic; SW, diastolic; DW, net; NW = SW - DW) were measured. Radionuclide ventriculography was safely performed with cardiac catheterization even in patients with congestive heart failure. Satisfactory PV loops were obtained by the advantage of simultaneous acquisition of RNV and analog data. Changes of ECG, PCG, volume, pressure and derived indices through one cardiac cycle were readily comparable each other. Peak LV pressure (mmHg) increased from 134 to 159 and then 182 by infusion of AII, but no change in heart rate was observed Emax was higher in normals and AP (mean 1.96 mmHg/ml/m2) than in OMI and MR (range of 0.85-1.36). SW increased in response to rise of LV pressure in all subjects. NW increased in normals and AP, but decreased in OMI and MR with relative increase in DW. In conclusion, this new system is feasible for repetitive studies under drug intervention, since it makes accurate PV loop under physiologic state, i.e. without pacing and volume overloading. Variable changes of SW, DW, and NW in response to afterloading were clarified, which may be useful for the evaluation of cardiac reserve in normal and diseased heart.


[Virus Manombo (Mg Ar 966), a provisionally new arbovirus isolated from Culicidae in Madagascar].
In April 1987, a virus strain was isolated from a pool of Mansonia uniformis caught on human bait, in a tropical primary rain forest area of the South-East coast of Madagascar. Antigenically, this virus may not be related to other known viruses, and constitutes a provisionally new Arbovirus called virus Manombo.


Impaired insulin-mediated vasorelaxation in diabetic Goto-Kakizaki rats is caused by impaired Akt phosphorylation.
Insulin resistance associated with Type 2 diabetes contributes to impaired vasorelaxation. Previously, we showed the phosphorylation of myosin-bound phosphatase substrate MYPT1, a marker of the vascular smooth muscle cell (VSMC) contraction, was negatively regulated by Akt (protein kinase B) phosphorylation in response to insulin stimulation. In this study we examined the role of Akt phosphorylation on impaired insulin-induced vasodilation in the Goto-Kakizaki (GK) rat model of Type 2 diabetes. GK VSMCs had impaired basal and insulin-induced Akt phosphorylation as well as increases in basal MYPT1 phosphorylation, inducible nitric oxide synthase (iNOS) expression, and nitrite/nitrate production compared with Wistar-Kyoto controls. Both iNOS expression and the inhibition of angiotensin (ANG) II-induced MYPT1 phosphorylation were resistant to the effects of insulin in diabetic GK VSMC. We also measured the isometric tension of intact and denuded GK aorta using a myograph and observed significantly impaired insulin-induced vasodilation. Adenovirus-mediated overexpression of constitutively active Akt in GK VSMC led to significantly improved insulin sensitivity in terms of counteracting ANG II-induced contractile signaling via MYPT1, myosin light chain dephosphorylation, and reduced iNOS expression, S-nitrosylation and survivin expression. We demonstrated for the first time the presence of Akt-independent iNOS expression in the GK diabetic model and that the defective insulin-induced vasodilation observed in the diabetic vasculature can be restored by the overexpression of active Akt, which advocates a novel therapeutic strategy for treating diabetes.


Chromosomal Mapping of Repetitive DNAs in Myiopsitta monachus and Amazona aestiva (Psittaciformes, Psittacidae) with Emphasis on the Sex Chromosomes.
Here, for the first time, we describe the karyotype of Myiopsitta monachus (Psittacidae, Arini). We found 2n = 48, corresponding to the lowest diploid number observed in Neotropical Psittaciformes so far, with an uncommonly large W chromosome homomorphic to the Z. In order to better understand the evolution of the sex chromosomes in this species, we applied several molecular cytogenetic approaches, including C-banding, FISH mapping of repetitive DNAs (several microsatellite repeats), and whole-chromosome painting on metaphases of M. monachus. For comparison, another species belonging to the same tribe but with a smaller W chromosome (A. aestiva) was also analyzed. The results show that the constitutive heterochromatin has a very diverse distribution pattern in these species revealing heterochromatic blocks in the centromeric region of all chromosomes and in most of the length of the W chromosome in A. aestiva, while in M. monachus they were found in interstitial and telomeric regions. Concerning the microsatellites, only the sequence (CG)n produced signals on the W chromosome of A. aestiva, in the distal region of both arms. However, in M. monachus, (CAA)n, (CAG)n, and (CG)n probes were accumulated on the W chromosome, and, in addition, the sequence (CAG)n also hybridized to heterochromatic regions in macrochromosomes, as well as in microchromosomes. Based on these results, we suggest that the increase in length of the W chromosome in M. monachus is due to the amplification of repetitive elements, which highlights their significant role in the evolutionary process of sex chromosome differentiation.


Microcarriers Based on Glycosaminoglycan-Like Marine Exopolysaccharide for TGF-β1 Long-Term Protection.
Articular cartilage is an avascular, non-innervated connective tissue with limited ability to regenerate. Articular degenerative processes arising from trauma, inflammation or due to aging are thus irreversible and may induce the loss of the joint function. To repair cartilaginous defects, tissue engineering approaches are under intense development. Association of cells and signalling proteins, such as growth factors, with biocompatible hydrogel matrix may lead to the regeneration of the healthy tissue. One current strategy to enhance both growth factor bioactivity and bioavailability is based on the delivery of these signalling proteins in microcarriers. In this context, the aim of the present study was to develop microcarriers by encapsulating Transforming Growth Factor-β1 (TGF-β1) into microparticles based on marine exopolysaccharide (EPS), namely GY785 EPS, for further applications in cartilage engineering. Using a capillary microfluidic approach, two microcarriers were prepared. The growth factor was either encapsulated directly within the microparticles based on slightly sulphated derivative or complexed firstly with the highly sulphated derivative before being incorporated within the microparticles. TGF-β1 release, studied under in vitro model conditions, revealed that the majority of the growth factor was retained inside the microparticles. Bioactivity of released TGF-β1 was particularly enhanced in the presence of highly sulphated derivative. It comes out from this study that GY785 EPS based microcarriers may constitute TGF-β1 reservoirs spatially retaining the growth factor for a variety of tissue engineering applications and in particular cartilage regeneration, where the growth factor needs to remain in the target location long enough to induce robust regenerative responses.


Fast-track development of vaccines for SARS-CoV-2: The shots that saved the world.
In December 2019, an outbreak emerged of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which leads to coronavirus disease 2019 (COVID-19). The World Health Organisation announced the outbreak a global health emergency on 30 January 2020 and by 11 March 2020 it was declared a pandemic. The spread and severity of the outbreak took a heavy toll and overburdening of the global health system, particularly since there were no available drugs against SARS-CoV-2. With an immediate worldwide effort, communication, and sharing of data, large amounts of funding, researchers and pharmaceutical companies immediately fast-tracked vaccine development in order to prevent severe disease, hospitalizations and death. A number of vaccines were quickly approved for emergency use, and worldwide vaccination rollouts were immediately put in place. However, due to several individuals being hesitant to vaccinations and many poorer countries not having access to vaccines, multiple SARS-CoV-2 variants quickly emerged that were distinct from the original variant. Uncertainties related to the effectiveness of the various vaccines against the new variants as well as vaccine specific-side effects have remained a concern. Despite these uncertainties, fast-track vaccine approval, manufacturing at large scale, and the effective distribution of COVID-19 vaccines remain the topmost priorities around the world. Unprecedented efforts made by vaccine developers/researchers as well as healthcare staff, played a major role in distributing vaccine shots that provided protection and/or reduced disease severity, and deaths, even with the delta and omicron variants. Fortunately, even for those who become infected, vaccination appears to protect against major disease, hospitalisation, and fatality from COVID-19. Herein, we analyse ongoing vaccination studies and vaccine platforms that have saved many deaths from the pandemic.


Seroprevalence of spotted fever group (SFG) rickettsiae infection in domestic ruminants in Khartoum State, Sudan.
Spotted fever group (SFG) rickettsiosis is caused by obligatory intracellular Gram-negative bacteria that belong to the genus Rickettsia. Ticks belonging to the family Ixodidae can act as vectors, reservoirs or amplifiers of SFG rickettsiae. This study was conducted to estimate the seroprevalence of SFG rickettsioses in cattle, sheep and goats from Khartoum State, Sudan. Blood samples were collected from a total of 600 animals (sheep, goats and cattle) from 32 different farms distributed in three locations in Khartoum State during the period January to December 2012. Sera were tested for antibodies against SFG rickettsiae using IFAT. The prevalence of seropositivity was 59.3% in sheep, 60.1% in goats and 64.4% in cattle. Season was significantly (P < 0.05) associated with seroprevalence of SFG rickettsiae in cattle during winter. The SFG rickettsiae antibodies prevalence was significantly higher in female compared with male in sheep, but there were no significant differences between male and female in either cattle or goats. The prevalence was significantly higher in adult animals compared with young in both sheep and goats. With regard to management system, there was a significant difference in the prevalence in cattle raised in closed system compared with those raised in semi-intensive system. In contrast, there was significant difference in the seroprevalence of SFG in sheep where the prevalence was higher in the sheep raised in semi-intensive system compared with those raised in close system. There was no significant difference in the seroprevalence in goats with regard to management systems. The unexpected high prevalence of SFG rickettsia antibodies in domestic ruminants sera suggest that the veterinary and public health impact of these agents in Sudan need further evaluation especially in humans.


Older Adults' Perceptions of Their Fall Risk and Prevention Strategies After Transitioning from Hospital to Home.
Falls are common adverse events following hospital discharge. However, prevention programs are not tailored for older patients transitioning home. To inform development of transitional fall prevention programs, nine older adults designated as being at risk of falls during hospitalization who were recently discharged home were asked about their perceptions of fall risk and prevention, as well as their knowledge and opinion of materials from the Centers for Disease Control and Prevention Stopping Elderly Accidents, Deaths & Injuries Initiative. Using the constant comparative method, five themes were identified: Sedentary Behaviors and Limited Functioning; Prioritization of Social Involvement; Low Perceived Fall Risk and Attribution of Risk to External Factors; Avoidance and Caution as Fall Prevention; and Limited Falls Prevention Information During Transition from Hospital to Home. Limited awareness of and engagement in effective fall prevention may heighten recently discharged older adults' risks for falls. Prevention programs tailored to the post-discharge period may engage patients in fall prevention, promote well-being and independence, and link hospital and community efforts. [Journal of Gerontological Nursing, 45(1), 23-30.].


[Splenectomy in hematologic diseases. A study of 70 cases].
The aim of this work was to report our own clinical experience and to compare it our results with those already published. This is a retrospective study of 70 splenectomies performed for hematologic diseases at the service des urgences viscerales of Ibn Rochd teaching hospital of Casablanca, between 1996 and 2001. The study included 70 patients. Splenectomy was performed for therapeutic reasons by laparotomy in 56 cases (80%) and bym laparoscopy in 14 cases (20%). The post-operative after-effects were mild in 81.4%. A patient died, however of pulmonary embolism. Splenectomy is an important tool in the management of patients suffering from hemolytic anemia, auto-immune thrombopenic purpura and other hemolytic anemias. Management by a multidisciplinary team is required to prevent a maximum of long and short-term post-operative complications and to offer the offer the best conditions for a successful splenectomy.


On fitting of mathematical models of cell signaling pathways using adjoint systems.
This paper concerns the problem of fitting of mathematical models of cell signaling pathways. Such models frequently take the form of a set of nonlinear ordinary differential equations. While the model is continuous-time, the performance index, used in the fitting procedure, involves measurements taken only at discrete-time moments. Adjoint sensitivity analysis is a tool that can be used for finding a gradient of a performance index in the space of the model's parameters. The paper uses a structural formulation of sensitivity analysis, especially dedicated for hybrid, continuous/discrete-time systems. A numerical example of fitting of the mathematical model of the NF-kB regulatory module is presented.


Ion channels in the thick ascending limb of Henle's loop.
The thick ascending limb of Henle's loop (TAL) is polarized with respect to its conductances. The luminal membrane contains a K+ conductance which is made up by the synchronous operation of 60- to 80-pS K+ channels. The basolateral membrane contains a chloride conductance. This conductance corresponds most likely to a 30- to 60-pS Cl- channel present in this membrane. Our knowledge on the properties of the K+ channels of these cells has been increased rapidly by patch clamp studies: these K+ channels are inwardly rectifying. They are highly selective for K+ over Na+, Li+ and many other cations. They do not conduct Rb+, Cs+, NH+4 or other larger cations. In fact, all these three cations as well as choline, tetraethylammonium, lidocaine, verapamil, diltiazem, quinine, quinidine and Ba2+ inhibit these K+ channels. As apparent from kinetic studies the mechanisms of inhibition are different for the various blockers. The TAL K+ channels are downregulated by increasing cytosolic Ca2+ activity. Cytosolic adenosine trisphosphate (ATP) has a similar effect. This ATP inhibition is Ca2+ dependent. The affinity to ATP is augmented by increasing Ca2+. Cytosolic alkalinity increases the open probability of these channels, and cytosolic acidification has the opposite effect. This pH dependence is very marked. A change by 0.2 pH units leads to a more than twofold change in the open-channel probability. The basolateral chloride conductance reflects the properties of an outwardly rectifying 30- to 60-pS Cl- channel. This channel behaves, in many respects, like the Cl- channels of a multitude of Cl- transporting epithelia. It is characterized by two open and two closed states. It is highly selective for Cl- as compared with larger anions, and it is inhibited reversibly by Cl- channel blockers such as 5-nitro-2-(3-phenylpropylamino)-benzoate.


Molecular forms of human growth hormone secreted in vivo: nonspecificity of secretory stimuli.
Several molecular forms of human GH (hGH) are present in blood, but their individual regulation is largely unknown. To examine the factors controlling the secretion of individual hGH variants, the relationship between the mixture of circulating hGH forms and the type of preceding secretory stimulus was studied in 18 normal subjects and 5 acromegalic patients. The stimuli employed were L-dopa, GH-releasing hormone-(1-40), exercise, spontaneous sleep-related and daytime secretory bursts, estrogens, and TRH in the acromegalic patients. Three monomeric hGH forms (22K, 20K, and acidic hGH) were identified in all samples; their mean relative proportions were 76.4%, 15.8%, and 7.9%, respectively. These proportions were similar in all subjects, regardless of stimulus, sex, or presence of acromegaly (P greater than 0.25). We conclude that the release of individual hGH forms is not stimulus specific, but, rather, that the secretory granule contents are released in toto upon somatotroph stimulation.


[Cardiac involvement in scleroderma].
It has been analyzed seven patients, five females and two males, affected by progressive systemic sclerosis. Their ages range from 35 to 60 years. Three of them correspond to the CREST syndrome named variant. There were made: physical examination, electrocardiogram, echocardiogram and radionuclide techniques such as: Thallium perfusion (T201) and ventriculography (Tc99). The cardiac examination of all the patients showed: Left myocardiopathy in six patients, as well right myocardiopathy in two of them. Four patients were affected by chronic cor pulmonale, due to pulmonary hypertension. All the patients had developed diffuse thallium perfusion defects as well, having abnormal resting left ventricular function in three patients and function abnormality from right ventricle in two patients. It is necessary to point out the importance of making such study systematically, even in the case cardiac symptoms absence.


Trajectories of 24-h movement guidelines from middle adolescence to adulthood on depression and suicidal ideation: a 22-year follow-up study.
The 24-h movement guidelines for youth and adults recommend the specific duration of physical activity, sedentary time, and sleep duration to ensure optimal health, but little is known about its relationship to mental health indicators. The aim of the study was to explore the association between 24-h movement guidelines in adolescence and its trajectories from middle adolescence (12-17 years old) to adulthood (33-39 years old) with depression and suicidal ideation in adulthood. This prospective cohort study included individuals who participated in Waves I (1994-1995) and V (2016-2018) of the National Longitudinal Study of Adolescent Health (Add Health) in the United States. Physical activity, screen time and sleep duration were measured using questionnaires. Adults were categorized as having depression if they had a self-reported history of depression and/or prescription medication-use for depression in the previous four weeks. Suicidal ideation was assessed by a self-reported single question in both waves. Poisson regression analyses were used to estimate the incidence rate ratio (IRR) of depression and suicidal ideation at adulthood, according to meeting specific and combinations of 24-h movement guidelines at Wave I and its trajectories from adolescence to adulthood. The study included 7,069 individuals (56.8% women). Adolescents who met physical activity guidelines and all three guidelines at middle adolescence had lower risk of depression (IRR = 0.84, 95%CI 0.72 to 0.98) and suicidal ideation (IRR = 0.74, 95%CI 0.55 to 0.99) at adulthood than those who did not meet any of these guidelines, respectively. Individuals who met the guidelines for screen time and all three guidelines in both adolescence and adulthood had lower risk of depression (screen time, IRR = 0.87, 95% CI 0.72 to 0.98; all three, IRR = 0.37, 95% CI 0.15 to 0.92) and suicidal ideation (screen time, IRR = 0.74, 95% CI 0.51 to 0.97; all three, IRR = 0.12, 95% CI 0.06 to 0.33) than those who never met the guidelines. Additionally, individuals who did not meet all three guidelines in adolescence but met the guidelines in adulthood had lower risk of suicidal ideation than those who never met the guidelines (IRR = 0.81, 95%CI 0.45 to 0.89). Our findings highlight the importance of promoting and maintaining adherence to the 24-h movement guidelines from middle adolescence to adulthood to prevent mental health problems. However, our findings must be interpreted carefully due to declared limitations, e.g., the self-reported assessments which are subject to sources of error and bias or that the dataset used to gauge meeting a guidelines (1994-1996) was made later (2016).


[Protective effect of licoflavone on gastric mucosa in rats with chronic superficial gastritis].
To evaluate the protective effect of licoflavone on gastric mucosa in rats with chronic superficial gastritis and explore the possible mechanism. SD rat models of chronic superficial gastritis was established by intragastric administration of 0.02% ammonia and long-term irregular diet. The rat models were then randomized into model group, vitacoenzyme group and 3 licoflavone groups of high, medium, and low doses. After 30 days of treatment, the gastric histopathology, mucosal lesions, scanning electron microscopy, mucin function production by the gastric mucosa epithelial cells, serum PGE(2) level and gastric microcirculation were assessed to evaluate the protective effect of licoflavone on gastric mucosa. Compared with normal control rats, the rat models of chronic superficial gastritis showed significantly higher gastric mucosal injury rate, histopathological scores and gastric mucin content. Licoflavone significantly ameliorated gastric pathology and increased serum PGE(2) level, enhanced acidic mucin secretion by the epithelial cells, and improved gastric microcirculation in the rat models. Licoflavone feeding suppresses gastric mucosa injury, protects and restores the injured mucosa in rats with chronic superficial gastritis, and these effects are related with the up-regulation of serum PGE(2) level.


Associations between CD160 polymorphisms and autoimmune thyroid disease: a case-control study.
Recent researches suggest that the CD160/HVEM/LIGHT/BTLA signaling pathway may contribute to the pathogeneses of autoimmune diseases, but the relationship between CD160 polymorphisms and autoimmune thyroid disease (AITD) has not been reported yet. This study aimed to evaluate the associations between CD160 polymorphisms and AITD. A total of 1017 patients with AITD (634 Graves' disease and 383 Hashimoto's thyroiditis) and 856 unrelated healthy controls were recruited into our study. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated through logistic regression analyses. The CD160 SNPs were detected using Hi-SNP high-throughput genotyping. There was a statistically significant difference between Graves' disease patients and the control group with respect to both the genotype distribution (P = 0.014) and allele frequency of rs744877 (P = 0.034). A significant association of CD160 rs744877 with AITD was observed before adjusted age and gender under a dominant model (OR = 0.79, 95%CI 0.66-0.95; P = 0.013) and an additive model (OR = 0.77, 95%CI 0.64-0.94, P = 0.008), and was also observed after adjusted age and gender under a dominant model (OR = 0.78, 95%CI 0.65-0.95; P = 0.011) and an additive model (OR = 0.76, 95%CI 0.63-0.93, P = 0.007). A significant association of rs744877 with Graves' disease was observed under an allele model (OR = 0.84, 95%CI 0.71-0.98, P = 0.027), a dominant model (OR = 0.74, 95%CI 0.60-0.91; P = 0.005), and an additive model (OR = 0.72, 95%CI 0.58-0.90, P = 0.004). Multivariate logistic regression analyses suggested that the association remained significant after adjustment for age and gender. However, rs744877 was not related to Hashimoto's thyroiditis. Furthermore, CD160 rs3766526 was not significantly related to either Graves' disease or Hashimoto's thyroiditis. This is the first identification of the association of CD160 rs744877 with Graves' disease. Our findings add new data to the genetic contribution to Graves' disease susceptibility and support the crucial role of the CD160/HVEM/LIGHT/BTLA pathway in the pathogenesis of Graves' disease.


Diagnostic and therapeutic value of short-term corticosteroid therapy in exacerbation of mustard gas-induced chronic bronchitis.
Chronic bronchitis is the most frequent late respiratory disease among Iranians exposed to mustard gas during the Iraq-Iran war. The aim of this study was to investigate efficacy of oral and intravenous corticosteroid therapy in improving lung function in mustard gas induced chronic bronchitis patients. 65 mustard gas-exposed chronic bronchitis patients, who were not responsive to standard treatments in exacerbation occasions, were randomly divided into two groups: an intravenous group (39 patients) receiving 500 mg intravenous methylprednisolone daily, and an oral group (26 patients) receiving 1 mg/kg oral prednisolone daily. Corticosteroid was tapered over the study period in both groups. Spirometery was performed on admission and on day 8 of therapy for assessment of effectiveness of therapy. There was significant improvement in spirometery indexes of both groups in approximately half of the patients over the study period. Furthermore, there was no difference between the pulse corticosteroid versus oral corticosteroid therapy in these patients. Since short-term corticosteroid therapy has a significant effect on lung function of almost fifty percent of patients with mustard gas-induced chronic bronchitis in exacerbation occasions, we suggest a short-term bolus steroid treatment to triage the patients into responders and non-responders for subsequent treatment.


Understanding the impact loading characteristics of a badminton lunge among badminton players.
The rapid and repetitive badminton lunges would produce strenuous impact loading on the lower extremities of players and these loading are thought to be the contributing factors of chronic knee injuries. This study examined the impact loading characteristics in various groups of badminton athletes performing extreme lunges. Fifty-two participants classified into male skilled, female skilled, male unskilled, and female unskilled groups performed badminton lunge with their maximum-effort. Shoe-ground kinematics, ground reaction forces, and knee moments were measured by using synchronised force platform and motion analysis system. A 2 (gender) x 2 (skill-level) factorial ANOVA was performed to determine the effects of different gender and different playing levels, as well as the interaction of two factors on all variables. Male athletes had faster approaching speed (male 3.87 and female 1.08 m/s), longer maximum lunge distance (male 1.47 and female 1.16 m), larger maximum (male 215.7 and female 121.65 BW/s) and mean loading rate (male 178.43 and female 81.77 BW/s) and larger peak knee flexion moment (male 0.75 and female 0.69) compared with female athletes (P < 0.001). Unskilled athletes exhibited smaller footstrike angle (skilled 45.78 and unskilled 32.35°), longer contact time (skilled 0.69 and unskilled 0.75 s), larger peak horizontal GRF (skilled 1.61 and unskilled 2.40 BW), smaller mean loading rate (skilled 150.15 and unskilled 110.05 BW/s) and larger peak knee flexion moment (P < .05; skilled 0.69 and unskilled 0.75 Nm/BW) than the skilled athletes. In addition, the interaction indicated greater peak GRF impact in female unskilled athletes compared with female skilled athletes (P < 0.001; female skilled 2.01 and female unskilled 2.95 BW), while there was no difference between male participants (P > 0.05; male skilled 2.19 and male unskilled 2.49 BW). These data suggested that male athletes and/or unskilled athletes experience greater impact loading rates and peak knee flexion moment during lunge compared with female and skilled athletes, respectively. This may expose them to higher risk of overuse injuries. Furthermore, female unskilled athletes seemed to be more vulnerable to lower extremity injuries.


Global oncofertility index-data gap slows progress.
The number of pediatric and young adult cancer survivors is increasing globally due to earlier diagnostics and expansion of targeted chemo- and biological-based therapeutics. As a consequence, cancer-related infertility and reproductive hormone loss is of increasing concern for both male and female survivors. We attempted to estimate the reproductive loss in oncofertility-practicing countries and to develop a global oncofertility index (OFI). This would allow an accounting of the level of urgency of the issue and would provide national comparisons of fertility loss, which differ based on the prevalence and/or diagnosis frequency and treatment variables by countries or region. While the goal is laudable, an index such as this is unachievable due to the lack of the kind of information that would be necessary to calculate such a meaningful index. Without this metric, we will be unable to assess how oncofertility concerns are being addressed and what lessons can be learned from countries that improve such an index over time.


Girls with Premature Thelarche Younger than 3 Years of Age May Have Stimulated Luteinizing Hormone Greater than 10 IU/L
Premature thelarche (PT) is defined as isolated breast development in girls before eight years of age. Gonadotropin-releasing hormone (GnRH) stimulation test is sometimes used to distinguish between PT and central precocious puberty (CPP), although the interpretation of the test at early ages is challenging. The objective of this study was to determine the follicle stimulating hormone (FSH) and luteinizing hormone (LH) responses to GnRH stimulation in girls with PT below 3 years of age. A standardized GnRH stimulation test, bone age and pelvic ultrasound were evaluated and those without pubertal progression after a minimum of one-year follow up were included in the study. On GnRH stimulation test, the median (range) baseline LH was 0.29 (0.10-0.74) IU/L, baseline FSH was 4.96 (3.18-7.05) mIU/mL, and the peak median LH was 5.75 (3.31-8.58) IU/L with the peak mean±standard deviation FSH was 40.38±20.37 mIU/mL. Among the patients, 33.3% (n=10) had baseline LH >0.3 IU/L, 67% (n=20) had peak LH >5 IU/l and 16.6% (n=5) >10 IU/L. The mean peak LH/FSH ratio was 0.17±0.09 and was ≤0.43 in all participants. Although consensus statements usually define baseline LH >0.3-0.5 IU/L, peak LH >5 IU/L, and LH/FSH ratios >0.66-1.0 as diagnostic cut-offs for CPP, in children below 3 years of age, the baseline and peak LH values may be similar to pubertal values, possibly due to mini-puberty. A dominant FSH response on GnRH stimulation test is more valuable than the peak LH response in the diagnosis of PT.


Geographic variation in a predator-induced defense and its genetic basis.
Predator-induced morphological defenses are a well-known form of phenotypic plasticity, but we continue to have a limited understanding of geographic variation in these responses and its genetic basis. Here we examine genetic variation and geographic differentiation in the inducible defenses of tadpoles (Rana pirica) in response to predatory salamander larvae (Hynobius retardatus). To do so, we crossed male and female frogs from a "mainland" Japanese island having predaceous salamanders and a more isolated island not having predaceous salamanders and raised resulting offspring in the presence and absence of H. retardatus. Mainland tadpoles exhibited a higher capacity to express the inducible morphology (a more bulgy body) than those from the predator-free island, and expression of the bulgy morph in mainland-island hybrids produced phenotypes that were intermediate to those produced by pure crosses. In addition, parental sex had no effect on expression of the bulgy morph. Our results support the hypothesis that geographic variation in inducible defenses is linked to the additive effects of autosomal alleles that are shaped by differences in historical exposure to the inducing predator.


The biosynthesis and secretion of precursor enamel protein by ameloblasts as visualized by autoradiography after tryptophan administration.
The incorporation of 3H-tryptophan into the inner enamel epithelium of newborn mouse incisor tooth organs has been studied in situ by light and electron microscopic autoradiography to determine the sites and kinetics of biosynthesis, migration, and secretion of precursor enamel protein during newborn mouse incisor tooth formation maxillary and mandibular incisor tooth amelogenesis was studied 5, 30, 60, 120, 240 minutes and 24 hours following the intraperitoneal injection of 3H-tryptophan. By 5 minutes, 40% of the total silver grains associated with the secretory ameloblasts were localized over the rough endoplasmic reticulum and 50% of the silver grains were localized over the Golgi apparatus. By 30 minutes, silver grains were observed predominately over condensing vacuoles and secretory granules within the forming Tomes' processes, and were also localized over the extracellular "granular" pre-enamel matrix. The enamel proteins were synthesized on membrane-bound polysomes, transferred within the cisternae of the rough endoplasmic reticulum and then accumulated in the inner saccules of the Golgi apparatus. The enamel proteins were than packaged in condensing vacuoles which subsequently became secretory granules which migrated to the lateral and apical secretory regions of the forming Tomes' processes. It was concluded from these in vivo studies that enamel protein were synthesized and subsequently secreted within 30 minutes. The initially secreted precursor enamel protein was localized over a material which demonstrated a granular or stippled ultrastructure. The labeled protein then was localized over the amorphous enamel matrix per se which contained the forming calcium hydroxyapatite crystals. We assumed, therefore, that there are two different ultrastructural forms of 3H-tryptophan containing extracellular enamel proteins and suggest that the granular or "stippled" form represents newly secreted precursor enamel protein.


Aptamer-based isolation and subsequent imaging of mesenchymal stem cells in ischemic myocard by magnetic resonance imaging.
Mesenchymal stem cells (MSC) seem to be a promising cell source for cellular cardiomyoplasty. We recently developed a new aptamer-based specific selection of MSC to provide "ready to transplant" cells directly after isolation. We evaluated MRI tracking of newly isolated and freshly transplanted MSC in the heart using one short ex vivo selection step combining specific aptamer-based isolation and labeling of the cells. Bone marrow (BM) was collected from healthy pigs. The animals were euthanized and the heart was placed in a perfusion model. During cold ischemia, immunomagnetic isolation of MSC from the BM by MSC-specific aptamers labeled with Dynabeads was performed within 2 h. For histological identification the cells were additionally stained with PKH26. Approx. 3 x 10(6) of the freshly aptamer-isolated cells were injected into the ramus interventricularis anterior (RIVA) and 5 x 10(5) cells were injected directly into myocardial tissue after damaging the respective area by freezing (cryo-scar). 3 x 10(6) of the aptamer-isolated cells were kept for further characterization (FACS and differentiation assays). 20 h after cell transplantation, MRI of the heart using a clinical 3.0 Tesla whole body scanner (Magnetom Trio, Siemens, Germany) was performed followed by histological examinations. The average yield of sorted cells from 120 ml BM was 7 x 10(6) cells. The cells were cultured and showed MSC-like properties. MRI showed reproducible artifacts within the RIVA-perfusion area and the cryo-scar with surprisingly excellent quality. The histological examination of the biopsies showed PKH26-positive cells within the areas which were positive in the MRI in contrast to the control biopsies. Immunomagnetic separation of MSC by specific aptamers linked to magnetic particles is feasible, effective and combines a specific separation and labeling technique to a "one stop shop" strategy.


First experience with the new high-frequency femtosecond laser system (LDV Z8) for cataract surgery.
The purpose of this work is to report our experience using the new Z8 laser system for femtosecond laser-assisted cataract surgery (FLACS) and to provide a sample of the performance and safety results using this new technology. This prospective observational study was performed at the Swiss Eye Research Foundation, Eye Clinic ORASIS, Reinach, Switzerland. Fourteen patients were subjected to unilateral FLACS. Capsulotomy and lens fragmentation were performed with the aid of the LDV Z8 femtosecond laser system. Ease of phacoemulsification (on a 4-point scale), completeness of capsulotomy (on a 10-point scale), time for preparation of femtosecond laser (minutes), effective phacoemulsification time (seconds), total duration of surgery (minutes), and safety of the procedure were evaluated. Ease of fragmentation and completeness of capsulotomy were estimated at 3.9 and 9.9, respectively. The preparation time for femtosecond was 3.6±0.7 minutes, effective phacoemulsification time was 2.5±3.1 seconds, and total duration of the FLACS procedure was 16.3±4.5 minutes. No major complications were observed. Approximately 42% of all patients (6/14) showed Descemet's folds directly postoperatively. FLACS with the LDV Z8 system was characterized by complete capsulotomy and highly effective and reproducible lens fragmentation. The safety of the procedure was very good as perceived by the surgeon operating in this observational case series. The cost to benefit ratio should be further debated by assessing the results of a major prospective study, which is required for valid evaluation of the efficiency and safety of the LDV Z8 laser system and of FLACS in general.


Site Occupancy Studies and Luminescence Properties of Emission Tunable Phosphors Ca9La(PO4)7:Re (Re = Ce3+, Eu2+).
The structure, site occupancies, and photoluminescence (PL) properties of Ce3+- or Eu2+-doped Ca9La(PO4)7 phosphors were investigated in this work. The powder X-ray diffraction (XRD) data and Rietveld refinement results showed that the phosphors are pure phases. The vacuum ultraviolet-ultraviolet-visible (VUV-UV-vis) spectra and decay curves confirmed that the Ce3+ and Eu2+ ions in Ca9La(PO4)7 occupied two crystal sites. Additionally, the tunable color can be obtained by adjusting doping concentration and altering temperature. The fabricated w-LED lamp based on Eu2+-doped Ca9La(PO4)7 phosphor gave properties with a color rendering index (CRI) of 85.26, CIE chromaticity coordinates of (0.358, 0.307), and color temperature (CCT) of 4329 K.