Outcomes of Ahmed glaucoma valve in paediatric glaucoma following congenital cataract surgery in persistent foetal vasculature.
To evaluate the outcomes of primary Ahmed glaucoma valve in refractory secondary glaucoma following congenital cataract surgery, particularly in persistent foetal vasculature. Retrospective review of paediatric patients after Ahmed glaucoma valve implantation for refractory post-lensectomy glaucoma in a tertiary referral centre in Spain. Surgical complications, additional and/or replacements of Ahmed glaucoma valve, intraocular pressure, cup-to-disc ratio, glaucoma medications and final visual acuity were studied. A total of 29 eyes, 41% with persistent foetal vasculature and 59% with non-persistent foetal vasculature were included with mean follow-up of 105 ± 67 and 74 ± 45 months, respectively, after first Ahmed glaucoma valve implant. Median survival time for the first Ahmed glaucoma valve was significantly lower in persistent foetal vasculature (7.0 ± 3.2 months) compared to non-persistent foetal vasculature (over 129 months), p = 0.001. The cumulative probability of success in persistent foetal vasculature and non-persistent foetal vasculature eyes with Ahmed glaucoma valve were, respectively, 37.5% and 88.2% at year 1 and 28.1% and 71.9% at year 5. Cox regression model suggested persistent foetal vasculature as predictive risk factor of time to Ahmed glaucoma valve failure (hazard ratio: 5.77, p = 0.004). Four eyes developed phthisis bulbi. Mean intraocular pressure prior glaucoma surgery was 32.66 ± 6.73 mmHg and decreased to 16.54 ± 2.75 mmHg (p < 0.001) at final visit. The most frequent early postoperative complication was severe hypotony (32.6%) which tended to be self-limiting. Vitreous haemorrhage was associated with persistent foetal vasculature (p = 0.024). Ahmed glaucoma valve replacements after complications and additional Ahmed glaucoma valve implantations due to unsatisfactory intraocular pressure were more common in the persistent foetal vasculature group. Eyes with persistent foetal vasculature and secondary glaucoma after congenital cataract surgery followed by AGV implantation had a higher number of complications and a decreased probability of success compared to the non-persistent foetal vasculature group. Both groups achieved a significant decrease in intraocular pressure; thus, Ahmed glaucoma valve may be considered as first-line treatment in refractory glaucoma following congenital cataract surgery.


Deinstitutionalization of long stay patients in a psychiatric hospital in Rio de Janeiro.
Critical Time Intervention (CTI) is a time-limited mental health intervention offered to people with mental disorders during critical/transition periods. This study assesses the impact of CTI-BR on social performance and quality of life within a population in the process of deinstitutionalization, after long-term hospitalization in a psychiatric institution. The study population was split into two groups, one of which received CTI plus the regular care. Results showed no advantage of the intervention compared to the regular programs provided by the institution. When study participants are analyzed as a group, we found positive improvement regarding their social functioning and self-perception of their mental-health. Results show that it is possible for elderly patients discharged from long-term psychiatric care to live in residential facilities in the community, supervised by clinical teams.


Influence of tissue sample dimensions on the swelling of the corneal stroma.
The kinetics of imbibition of unbuffered 1% NaCl at 37 degrees C by whole ovine corneal stroma preparations were compared to those for square samples of stromas with side dimensions of 4, 6, 8, 10 and 13 mm. The rates and extent of swelling over a 24-hour period were proportionately greater for samples with smaller dimensions. After 24 h, the relative magnitude of the changes in wet mass ranged from 465% for complete stromas to 1,185% for 4 x 4-mm tissue squares. This size-dependent difference in swelling may, in part, account for differences between previous studies.


Molecular determinants of transient and reversible induced up-regulation of CaCDR1 in azole susceptible clinical isolates of Candida albicans.
The present study examines the molecular mechanism underlying in vitro-induced resistance to FLC (fluconazole), KTC (ketaonazole), MCZ (miconazole) and CHX (cycloheximide) in AS (azole-susceptible) strains of Candida albicans when exposed to CaCDR1/CaCDR2 inducers like FPZ (fluphenazine) and steroids [PRG (progesterone) and β-EST (β-oestradiol)]. By employing spot and checkerboard titre assays, we provide evidence of an in vitro-induced antagonism between tested drugs and inducers, which was accompanied with a concomitant increase in CaCDR1 and CaCDR2 transcript levels. Notably, unlike AS isolates, parental WT (wild-type) and Δcdr2 null strains, Δcdr1 as well as Δcdr1/Δcdr2 nulls, when challenged with the inducers could not display antagonism. Our results validated by Northern blotting, reporter gene transcription and TRO (transcription run on) assays show that in vitro-induced antagonism between tested drugs and inducer in AS isolates was mainly due to a transient and reversible transcriptional activation of CaCDR1. Notwithstanding our earlier observation that consistent high transcript levels of CaCDR1 in clinical AR (azole-resistant) isolates were maintained due to the combination of its transcriptional activation and enhanced mRNA stability via elongated poly(A) tails, this study shows that transient and reversible transcriptional activation of CaCDR1 was the major determinant of induced antagonism in AS isolates. The distinct strategies between sustained (in AR isolates) and transiently induced resistance mechanisms (in AS isolates) adopted by Candida should become useful in improving therapeutic approaches.


Discrepancies in rib fracture severity between radiologist and surgeon: A retrospective review.
Chest computed tomography (CT) scans are important for the management of rib fracture patients, especially when determining indications for surgical stabilization of rib fractures (SSRFs). Chest CTs describe the number, patterns, and severity of rib fracture displacement, driving patient management and SSRF indications. Literature is scarce comparing radiologist versus surgeon rib fracture description. We hypothesize there is significant discrepancy between how radiologists and surgeons describe rib fractures. This was an institutional review board-approved, retrospective study conducted at a Level I academic center from December 2016 to December 2017. Adult patients (≥18 years of age) suffering rib fractures with a CT chest where included. Basic demographics were obtained. Outcomes included the difference between radiologist versus surgeon description of rib fractures and differences in the number of fractures identified. Rib fracture description was based on current literature: 1, nondisplaced; 2, minimally displaced (<50% rib width); 3, severely displaced (≥50% rib width); 4, bicortically displaced; 5, other. Descriptive analysis was used for demographics and paired t test for statistical analysis. Significance was set at p = 0.05. Four hundred and ten patients and 2,337 rib fractures were analyzed. Average age was 55.6(±20.6); 70.5% were male; median Injury Severity Score was 16 (interquartile range, 9-22) and chest Abbreviated Injury Scale score was 3 (interquartile range, 3-3). For all descriptive categories, radiologists consistently underappreciated the severity of rib fracture displacement compared with surgeon assessment and severity of displacement was not mentioned for 35% of rib fractures. The mean score provided by the radiologist was 1.58 (±0.63) versus 1.78 (±0.51) by the surgeon (p < 0.001). Radiologists missed 138 (5.9%) rib fractures on initial CT. The sensitivity of the radiologist to identify a severely displaced rib fracture was 54.9% with specificity of 79.9%. Discrepancy exists between radiologist and surgeon regarding rib fracture description on chest CT as radiologists routinely underappreciate fracture severity. Surgeons need to evaluate CT scans themselves to appropriately decide management strategies and SSRF indications. Prognostic/Diagnostic Test, level III.


Analysis of genetic markers of N. gonorrhoeae resistance to beta-lactam antibiotics.
A complex method for detection of genetic markers of N. gonorrhoeae resistance to penicillin was developed. Mutations in penA and ponA genes were detected by minisequencing reaction with subsequent detection of reaction products by MALDI-TOF mass spectrometry. This approach was tested on 31 clinical strains of N. gonorrhoeae with minimum inhibitory concentration of penicillin from 0.03 to 8 microg/ml and higher. Mutations in penA and ponA genes in moderately resistant strains were shown (minimum inhibitory concentration up to 0.5 microg/ml) and mutations in penA, ponA, and penB genes in resistant strains (minimum inhibitory concentration more than 1.0 microg/ml). beta-Lactamase genes were detected in 4 strains with high resistance (minimum inhibitory concentration 4-8 and more microg/ml). Correlation between microbiological resistance and presence of respective mutations in the studied locuses was detected.


Methods in laboratory investigation. Isolation of guinea pig monocytes and Kurloff cells: characterization of monocyte subsets by morphology, cytochemistry, and adherence.
Guinea pig mononuclear cells were separated from peripheral blood using high-density Ficoll-Hypaque, following which the monocytes and Kurloff cells were isolated using counterflow centrifugation elutriation and Percoll gradient centrifugation. Monocytes were obtained in four counterflow centrifugation elutriation fractions. Small monocytes (283 micron3) constituted 33% of all monocytes and were acid phosphatase negative, nonadherent cells with a scant cytoplasm but characteristic reniform nucleus. Although present in low purity after counterflow centrifugation elutriation, they were enriched using Percoll gradients to 35%. Large monocytes (317 micron3) comprised 41% of all monocytes and were obtained in 81% purity by counterflow centrifugation elutriation. They were adherent cells positive for acid phosphatase and nonspecific esterase. Peroxidase-positive cells constituted 41 and 33% of the small and large monocytes, respectively. Intermediate-sized monocytes (300 micron3) comprised a mixture of monocytes with characteristics of both small and large monocytes. Very large monocytes (354 micron3) were peroxidase-negative, strongly adherent cells with a distinctive morphology characterized by a spherical nucleus and highly vacuolated cytoplasm. They comprised 7% of the total monocytes and are a heretofore unrecognized cell type in the circulation. These procedures also isolated Kurloff cells in high purity and yield. Kurloff cells are distinct to the guinea pig and were nonadherent cells that did not stain for acid phosphatase, peroxidase, or nonspecific esterase. This is the first report of the successful isolation of Kurloff cells as well as monocytes other than human into fractions that differ in size and function.


The Molecular Data Organization for Publication (MDOP) R package to aid the upload of data to shared databases.
Molecular identification methods, such as DNA barcoding, rely on centralized databases populated with morphologically identified individuals and their referential nucleotide sequence records. As molecular identification approaches have expanded in use to fields such as food fraud, environmental surveys, and border surveillance, there is a need for diverse international data sets. Although central data repositories, like the Barcode of Life Datasystems (BOLD), provided workarounds for formatting data for upload, these workarounds can be taxing on researchers with few resources and limited funding. To address these concerns, we present the Molecular Data Organization for Publication (MDOP) R package to assist researchers in uploading data to public databases. To illustrate the use of these scripts, we use the BOLD system as an example. The main intent of this writing is to assist in the movement of data, from academic, governmental, and other institutional computer systems, to public locations. The movement of these data can then better contribute to the global DNA barcoding initiative and other global molecular data efforts.


An infusion set for parenteral nutrition.
An attachment for a standard intravenous infusion set is described. It allows delivery of carbohydrate and amino-acid solutions in a manner that favours maximum utilization and reduces the risks of metabolic complications. It also permits, with ease, repeated alterations of infusion regimes when this is considered necessary.


Proximal and distal dog coronary arteries respond differently to basal EDRF but not to NO.
Experiments were designed to analyze the effects of endothelium-derived relaxing factor(s) (EDRF; released basally or on stimulation with acetylcholine) and nitric oxide (NO) on smooth muscle of coronary arteries of different diameter. During contractions of the bioassay ring evoked with prostaglandin F2 alpha, the relaxations caused by basal EDRF were greater in the distal than in the proximal coronary arteries, whereas there was no difference in response to the EDRF released by acetylcholine. During direct superfusion, NO caused similar relaxations in proximal and distal coronary artery rings. Optimal tension, prostaglandin F2 alpha-induced contractions, and relaxations caused by sodium nitroprusside were comparable in both preparations. In rings of proximal and distal coronary artery studied in organ chambers, acetylcholine caused comparable endothelium-dependent, whereas sodium nitroprusside and NO cause comparable endothelium-independent relaxations. These experiments indicate a difference in response of different-sized coronary arteries to basally released EDRF and suggest that the basally released factor differs from NO.


Location of the meso-pancreatoduodenum as a regional lymphatic basin for pancreatic head carcinoma.
The meso-pancreatoduodenum is the primary site of tumor infiltration in patients with pancreatic head cancer, with numerous patients exhibiting lymph node metastases. Effective dissection of the regional lymphatic basin requires knowledge of the patterns of the arterial branches. The present study examined the patterns of the arteries feeding the pancreatic head and the distribution of the meso-pancreatoduodenum. The present study included 123 patients with pancreatic cancer who underwent contrast-enhanced preoperative 64-multidetector-computed tomography to determine the routes of the inferior pancreaticoduodenal and first jejunal arteries. Surgical specimens and cadavers were also evaluated histologically to clarify the distribution of the meso-pancreatoduodenum. The feeding arteries were divided into three types, with 64.2% of patients having type A, 28.4% having type B and 7.3% having type C branches. The branches emerged from the back or left side of the superior mesenteric artery and ran to the far side of the pancreatic head in an arc. Consequently, the meso-pancreatoduodenum had a roll-shaped appearance, surrounding the trunk arteries and extending to the left side of the superior mesenteric artery. Dissecting the right and left sides of the superior mesenteric artery during lymphadenectomy could improve the effectiveness of resection.


BOLD magnetic resonance imaging in nephrology.
Magnetic resonance (MR) imaging, a non-invasive modality that provides anatomic and physiologic information, is increasingly used for diagnosis of pathophysiologic conditions and for understanding renal physiology in humans. Although functional MR imaging methods were pioneered to investigate the brain, they also offer powerful techniques for investigation of other organ systems such as the kidneys. However, imaging the kidneys provides unique challenges due to potential complications from contrast agents. Therefore, development of non-contrast techniques to study kidney anatomy and physiology is important. Blood oxygen level-dependent (BOLD) MR is a non-contrast imaging technique that provides functional information related to renal tissue oxygenation in various pathophysiologic conditions. Here we discuss technical considerations, clinical uses and future directions for use of BOLD MR as well as complementary MR techniques to better understand renal pathophysiology. Our intent is to summarize kidney BOLD MR applications for the clinician rather than focusing on the complex physical challenges that functional MR imaging encompasses; however, we briefly discuss some of those issues.


High-Rate Assembly of Nanomaterials on Insulating Surfaces Using Electro-Fluidic Directed Assembly.
Conductive or semiconducting nanomaterials-based applications such as electronics and sensors often require direct placement of such nanomaterials on insulating surfaces. Most fluidic-based directed assembly techniques on insulating surfaces utilize capillary force and evaporation but are diffusion limited and slow. Electrophoretic-based assembly, on the other hand, is fast but can only be utilized for assembly on a conductive surface. Here, we present a directed assembly technique that enables rapid assembly of nanomaterials on insulating surfaces. The approach leverages and combines fluidic and electrophoretic assembly by applying the electric field through an insulating surface via a conductive film underneath. The approach (called electro-fluidic) yields an assembly process that is 2 orders of magnitude faster compared to fluidic assembly. By understanding the forces on the assembly process, we have demonstrated the controlled assembly of various types of nanomaterials that are conducting, semiconducting, and insulating including nanoparticles and single-walled carbon nanotubes on insulating rigid and flexible substrates. The presented approach shows great promise for making practical devices in miniaturized sensors and flexible electronics.


Comparison of fetal and neonatal growth curves in detecting growth restriction.
To evaluate the outcome of intrauterine growth restriction (IUGR) infants with abnormal pulsatility index of the umbilical artery according to the neonatal birth weight/gestational age standards and the intrauterine growth charts. We analyzed 53 pregnancies with severe IUGR classified as group 2 (22 IUGR: abnormal pulsatility index and normal fetal heart rate) and group 3 (31 IUGR: abnormal pulsatility index and fetal heart rate). Neonatal birth weight/gestational age distribution, body size measurements, maternal characteristics and obstetric outcome, and neonatal major and minor morbidity and mortality were compared with those obtained in 79 singleton pregnancies with normal fetal growth and pulsatility index, matched for gestational age (appropriate for gestational age [AGA] group). Differences were analyzed with the chi(2) test and the Student t test. Differences between means corrected for gestational age in the different groups were assessed by analysis of covariance test. A P<.05 was considered significant. At delivery, using the neonatal standards, 25 of 53 (47%) IUGR showed a birth weight above the 10th percentile (IUGR(AGA)), whereas in 28, birth weight was below the 10th percentile (IUGR small for gestational age [SGA]-IUGR(SGA)). All body size measurements were significantly higher in AGA than in IUGR(AGA) and IUGR(SGA). Forty-nine of 79 (62%) AGA and 49 of 53 (92%) IUGR were admitted to the neonatal intensive care unit (P<.001). One of 79 (1%) AGA and 6 of 53 (11%) IUGR newborns died within 28 days (P<.02). Major and minor morbidity was not different. This study shows that neonatal outcome is similar in IUGR of the same clinical severity, whether or not they could be defined AGA or SGA according to the neonatal standards. Neonatal curves are misleading in detecting low birth weight infants and should be used only when obstetric data are unavailable. II.


[Enterobacterial susceptibility to antibiotics in northern Lebanon (1998-2001)].
The purpose of this study was to assess the epidemiology of local enterobacterial susceptibility to antibiotics. Between 1 January, 1998, and 31 December, 2001, we studied the sensitivity of 2,238 Enterobacteria to 26 different antibiotic agents in northern Lebanon, in the Microbiology department and Laboratory of the Islami Hospital, Tripoli, Lebanon. We used the diffusion disk method and complied with the guidelines of the French Microbiology Society antibiogram committee. Urinary samples were the most frequent source (67.5%), followed by blood cultures (12.7%). The dominant species in blood cultures was S. typhi (44.7%). We found 194 strains that produced extended-spectrum beta lactamases (ESBL), with the highest prevalence in Serratia spp. (44.3%), followed by Klebsiella pneumoniae (23.7%), Escherichia coli (20.7%) and Klebsiella oxytoca (11.3%). The global susceptibility of these strains to aminopenicillin was 15%; it reached 30% when combined with clavulanic acid. Susceptibility of the ESBL strains to these agents was 0%. The global susceptibility (and that of the ESBL strains, when greater than 0%) to other antibiotics was as follows: ticarcillin 38.5%, piperacillin 38.5%, piperacillin-tazobactam 88% (64%), imipenem 99.4%, (100%), cefalexin 41%, cefoxitin 65% (40.3%), cefuroxime 75%, amikacin 89%, chloramphenicol 30%, gentamicin 78% (42%), tetracycline 28% (16%), minocycline 30% (18.4%), colistin 67% (75%), nitrofuran 40% (45%), cotrimoxazol 40% (13%), nalidixic acid 53% (5.6%), pefloxacin 63% (23%), ciprofloxacin 71% (39%), and levofloxacin 72% (47%).


Influence of Testing Parameters on In Vitro Tramadol Release from Poloxamer Thermogels using the Immersion Cell Method.
The immersion cell is an in vitro performance test of drug release from semisolids. Several studies made use of immersion cells to investigate drug release from thermosensitive Poloxamer-based gels; however, specifications on the parameter setting are not yet available. Therefore, the aim of this study was to evaluate the influence of testing parameters on tramadol (a model drug) release, release rate, and dissolution efficiency (DE) from Poloxamer gels, using immersion cells. The thermosensitive gelling formulation showed batch-to-batch uniformity of gelling behavior, drug content, and drug release. The use of a membrane in the immersion cell resulted in slower drug release as compared to the absence of a membrane. Moreover, the faster the paddle rotation, the faster the drug release was. Membrane thickness showed a strong and significant linear relationship with corresponding DE values (Pearson's correlation coefficient, r = -0.9470; p = 0.004). Factors that did not influence drug release include paddle position, i.e., distance between paddle and membrane, as well as membrane mean pore size. This study sets forth the importance of carefully controlling the following parameters including presence/absence of membrane, paddle rotation speed, and membrane thickness during the setup of release experiments from gels using immersion cells.


Failure of dietary alpha-difluoromethylornithine to inhibit gastric carcinogenesis in rats after 8 weeks of treatment with N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride.
The modifying effects of alpha-difluoromethylomithine (DFMO) on glandular stomach carcinogenesis after initiation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride were investigated in male outbred Wistar rats. Animals were simultaneously given MNNG solution (100 ppm) as their drinking water and diet supplemented with 10% sodium chloride for 8 weeks, and administered DFMO (dietary levels of 2000 ppm or 500 ppm) and tap water for the following 70 weeks. The DFMO treatment did not show any tendency to inhibit the development of gastric adenocarcinomas. The incidences and multiplicities of atypical hyperplasias in the glandular stomachs were also comparable in all groups of rats given MNNG/sodium chloride. Neither gastric carcinomas nor atypical hyperplasias were observed without the carcinogen treatment. Thus, DFMO did not exert any inhibitory effects when given during the post-initiation phase of two-stage glandular stomach carcinogenesis in rats initiated with MNNG and sodium chloride for 8 weeks.


Adaptive regulation of taurine and beta-alanine uptake in a human kidney cell line from the proximal tubule.
1. The underlying mechanisms involved in the adaptive regulation of beta-amino acid uptake in the human proximal tubule were examined by use of an immortalized human embryonic kidney epithelial cell line (IHKE). 2. The results indicated that the adaptive response to maintain whole-body taurine homeostasis occurs predominantly via changes in the activity of the high-affinity taurine transport system by alterations in the uptake capacity and with an unaffected half-saturation constant. An adaptive response was not observed for the structurally related beta-alanine. 3. Only colchicine, which interferes with microtubule organization, was capable of blocking the response to alterations of taurine in cell medium, whereas inhibition of protein and nucleic acid synthesis by cycloheximide and actinomycin D, respectively, did not change the adaptive pattern. 4. Phorbol 12-myristate 13-acetate (PMA), mimicking the effects of diacylglycerol, induced inhibition of both beta-alanine and taurine uptake. By contrast, the Ca2(+)-ionophore A23187, mimicking the effects of IP3, only stimulated the uptake of taurine but not the influx of beta-alanine. However, the effect of PMA down-regulation and A23187 up-regulation was rapid and short-lived in contrast to the adaptive response, suggesting that the inositol phospholipid pathway involving diacetylglycerol and IP3 is less likely to be linked directly to the adaptive regulation, but rather plays a role in short-term regulation.


Does CYP2C19 polymorphisms affect neurological deterioration in stroke/TIA patients?: A systematic review and meta-analysis of prospective cohort studies.
The association between cytochrome P450 2C19 (CYP2C19) polymorphisms and neurological deterioration in stroke or transient ischemic attack (TIA) patients is not completely understood. Hence, we performed a systematic review and meta-analysis of prospective cohort studies to quantify this association. PubMed, Cochrane Library, Excerpta Medica Database, China National Knowledge Infrastructure and WanFang databases were searched for studies published up to April 2019. Prospective cohort studies that reported an association between CYP2C19 polymorphisms and neurological deterioration in stroke/TIA patients were included. Data on risk ratio (RR) and 95% confidence intervals (CI) were extracted and pooled by the authors. Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. Twelve eligible studies were included. Twelve studies reported CYP2C19∗2, ∗3 loss-of-function alleles and 5 studies reported CYP2C19∗17 gain-of-function allele. Compared to non-carriers, carriers of CYP2C19∗2, ∗3 loss-of-function alleles had a significantly higher risk of neurological deterioration (RR, 1.63; 95%CI, 1.32-2.02). Conversely, carriers of CYP2C19∗17 gain-of-function allele had a significantly lower risk of neurological deterioration (RR, 0.520; 95%CI, 0.393-0.689) compared to non-carriers. This meta-analysis demonstrated that the carriers of CYP2C19∗2, ∗3 loss-of-function alleles have an increased risk of neurological deterioration compared to non-carriers in stroke or TIA patients. Additionally, CYP2C19∗17 gain-of-function allele can reduce the risk of neurological deterioration.


[Effect of the thyroid in the development of intestinal hydroxylases].
The authors studied the saccharidase levels in the intestines of rats during the perinatal period. Sucrase and maltase values increase with advancing time, while lactase values decrease also age-dependently. The thyroid gland has a decisive role in the intestinal maturation of fats. In an assessment of circulating blood thyroxin levels, the authors found that the amount of thyroxin at birth is practically undetectable (less than 0,05 mug/100 ml expressed in iodine), rapidly increasing up to adult levels (3,8 mug/100 ml) 22 days after birth.


Promoting Cardiac Regeneration and Repair Using Acellular Biomaterials.
Ischemic heart disease is a common cause of end-stage heart failure and has persisted as one of the main causes of end stage heart failure requiring transplantation. Maladaptive myocardial remodeling due to ischemic injury involves multiple cell types and physiologic mechanisms. Pathogenic post-infarct remodeling involves collagen deposition, chamber dilatation and ventricular dysfunction. There have been significant improvements in medication and revascularization strategies. However, despite medical optimization and opportunities to restore blood flow, physicians lack therapies that directly access and manipulate the heart to promote healthy post-infarct myocardial remodeling. Strategies are now arising that use bioactive materials to promote cardiac regeneration by promoting angiogenesis and inhibiting cardiac fibrosis; and many of these strategies leverage the unique advantage of cardiac surgery to directly visualize and manipulate the heart. Although cellular-based strategies are emerging, multiple barriers exist for clinical translation. Acellular materials have also demonstrated preclinical therapeutic potential to promote angiogenesis and attenuate fibrosis and may be able to surmount these translational barriers. Within this review we outline various acellular biomaterials and we define epicardial infarct repair and intramyocardial injection, which focus on administering bioactive materials to the cardiac epicardium and myocardium respectively to promote cardiac regeneration. In conjunction with optimized medical therapy and revascularization, these techniques show promise to upregulate pathways of cardiac regeneration to preserve heart function.


Evaluation of a dynamic dissolution/permeation model: Mutual influence of dissolution and barrier-flux under non-steady state conditions.
Combined dissolution/permeation testing is gaining increasing attention as an in vitro tool for predictive performance ranking of enabling oral formulations. The current aim was to study how in vitro drug permeation evolves under conditions, where the donor concentration is changing (non-steady state). To this end, a model case was construed: compacts of pure crystalline hydrocortisone methanolate (HC·MeOH) of slow release rates were prepared, and their dissolution and permeation determined simultaneously in a side-by-side setup, separated by a biomimetic barrier (Permeapad®). This was compared to a corresponding setup for a suspension of micronized hydrocortisone (HC). The HC suspension showed constant dissolved HC concentration and constant flux across the barrier, representing the permeation-limited situation. For the HC·MeOH compacts, various dynamic scenarios were observed, where dissolution rate and flux influenced each other. Interestingly, for all the dynamic scenarios, the incremental flux values obtained correlated nicely with the corresponding actual donor concentrations. Furthermore, donor depletion was tested using a HC solution. The dynamic interplay between decrease in donor concentration (down to less than 10% of the initial concentration) and flux was studied. The experiences gained are discussed in terms of further developing combined dissolution/permeation setups.


High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate.
Sulphoraphane (SF), a naturally occurring isothiocyanate, is a potent anticarcinogen in animal experiments. The mechanism of action of sulphoraphane includes induction of Phase 2 detoxification enzymes, inhibition of carcinogen-activating Phase 1 enzymes, induction of apoptosis and cell cycle arrest, and anti-inflammation. We have recently found that it was accumulated in mammalian cells by up to several hundred-fold over the extracellular concentration, primarily by conjugation with intracellular GSH. The intracellular accumulation levels of SF can reach millimolar concentrations. The anticarcinogenic activity of SF is at least partly dependent on its accumulation levels in cells. Here we show, however, that the accumulated SF was rapidly exported mainly in the form of GSH conjugate (GS-SF) in cultured human cells. It appeared that to sustain the intracellular accumulation levels required a continuous uptake of SF to offset the rapid export of SF/GS-SF. These findings may have important implications for the development of an effective dosing regimen for SF. Moreover, the export was temperature-sensitive and was inhibited by known inhibitors of membrane pumps, suggesting the involvement of such a pump in exporting accumulated SF/GS-SF. Indeed, studies with human leukemia cells (HL60) with or without overexpression of multidrug resistance associated protein-1(MRP-1) and human myeloma cells (8226) with or without overexpression of P-glycoprotein-1 (Pgp-1) indicated that both MRP-1 and Pgp-1 are involved in the export of intracellular SF/GS-SF.


Genomic predictors of remission to antidepressant treatment in geriatric depression using genome-wide expression analyses: a pilot study.
This first pilot study of genome-wide expression as predictor of antidepressant response in late-life depression examined genome-wide transcriptional profiles in a randomized placebo-controlled trial of combined methylphenidate and citalopram. Genome-wide transcriptional profiles were examined in peripheral blood leukocytes sampled at baseline and 16 weeks from 35 older adults with major depression, who were randomized to methylphenidate + citalopram, citalopram + placebo, or methylphenidate + placebo. Methylphenidate doses ranged between 10 and 40 mg/day, and citalopram doses ranged between 20 and 60 mg/day. Remission was defined as Hamilton Depression Rating Scale score of 6 or below. Early remission was achieved in the first 4 weeks of treatment. We hypothesized that differential gene expression at baseline can predict antidepressant response. We analyzed gene expression in 24 remitters and 11 non-remitters. At baseline, we found three genes showing higher expression in all remitters versus non-remitters that satisfied the established level of significance: a fold change of 2 and p-value of 0.05 that included HLA-DRB5, SELENBP1, and LOC388588. Two gene transcripts showed higher expression in early remitters at baseline compared with non-remitters. The first gene was CA1 carbonic anhydrase gene, on chromosome 8 involved in respiratory function (fold change 2.54; p = 0.03). The second gene was the SNCA-α-synuclein gene, implicated, which binds to dopamine transporter (fold change 2.1; p = 0.03). Remission to antidepressants in geriatric depression may be associated with a particular gene expression profile in monoaminergic and metabolic pathways and needs to be replicated in a larger sample.


Thallium-avid cerebral radiation necrosis.
Thallium imaging has been proposed as a noninvasive method to distinguish recurrent tumor from cerebral radiation necrosis in patients who have undergone radiation therapy. Previous reports have supported the intuitive hypothesis that metabolically active tumor tissue would accumulate Tl-201 to a much higher degree than nonviable necrotic tissue. A case of biopsy-proven cerebral radiation necrosis is presented demonstrating a degree of Tl-201 avidity previously thought to be diagnostic of recurrent tumor. Based on this finding, it is concluded that a high degree of Tl-201 uptake does not exclude the diagnosis of cerebral radiation necrosis.


Histone deacetylase 4 alters cartilage homeostasis in human osteoarthritis.
Osteoarthritis (OA) is the most common degenerative joint disorder, and a major cause of pain and disability among the elderly. Histone deacetylase 4 (HDAC4) has been shown to be a key regulator of chondrocyte hypertrophy during skeletogenesis. The aims of present study were to investigate the expression of HDAC4 in normal and OA cartilage and its potential roles during OA pathogenesis. The knee cartilage specimen (a total of 18, 12 female and 6 male) were obtained from primary OA patients undergoing total knee arthroplasty (TKA) and normal donors. By using immunohistochemistry staining, we detected the expression patterns of HDAC4 in OA cartilage and normal cartilage respectively. To assess the potential roles of HDAC4, HDAC4 expression in human chondrosarcoma cells (SW1353) was down-regulated by transfecting small interference RNA (siRNA), thereafter, cells were treated with IL-1β or TNF-α, and the expressions of several matrix-degrading enzymes and anabolic factors were examined by using quantitative PCR. The expression of HDAC4 was observed in the OA cartilage, whereas it was barely detected in the normal cartilage. The extent of HDAC4 expression had a statistically negative correlation with OA severity. We further explored that the reduction of HDAC4 level led to a significant repression of proinflammation cytokines induced up-regulated expressions of matrix-degrading enzymes (MMP1 (Matrix metalloproteinase 1), MMP3 (Matrix metalloproteinase 3) , MMP13 (Matrix metalloproteinase 13), ADAMTS4 (aggrecanase 1) and ADAMTS5 (aggrecanase 2)) in SW1353 in vitro. Moreover, knockdown of HDAC4 inhibited the expression of some anabolic genes (such as aggrecan). In this study, our findings suggest that the abnormal expression of HDAC4 in osteoarthritic cartilage might be implicated in promoting catabolic activity of chondrocyte, which is associated with OA pathogenesis. Thus, our findings give a new insight into the mechanism of articular cartilage damage, and indicate that HDAC4 might be a potential target for the therapeutic interventions of OA.


Intraoral vertical ramus osteotomy for correction of mandibular prognathism: long-term stability.
Various techniques and modifications have been introduced in the treatment of mandibular prognathism. However, there are still few reports concerning long-term stability, especially using the intraoral vertical ramus osteotomy (IVRO) method. The purpose of this study was to investigate the long-term stability for correction of mandibular prognathism using IVRO. Twenty-five mandibular prognathism patients were treated by bilateral IVRO, and were evaluated cephalometrically by reference to the menton. A set of 3 standardized lateral cephalograms were obtained from each subject preoperatively (T1), immediately postoperatively (T2), and after 2 years postoperatively (T3). Relapse was defined as forward movement of menton after the 2-year follow-up. The mean setback of the menton was 12.8 mm in horizontal direction and 0.9 mm downward in vertical direction. The average follow-up was 33.9 months. The mean relapse was 1.3 mm (10.2% = 1.3 of 12.8) in forward direction and 0.6 mm in upward direction. There was no significant movement in the vertical direction. However, significant relapse was shown in the horizontal direction, even though the amount was small. The long-term stability of our present study suggested that IVRO is useful for correction of mandibular prognathism.


ICOS expression by activated human Th cells is enhanced by IL-12 and IL-23: increased ICOS expression enhances the effector function of both Th1 and Th2 cells.
Previous mouse studies have shown that IL-4 increases the expression of ICOS on activated Th cells, resulting in enhanced ICOS expression on Th2 cells. In this study, we show that ICOS expression on human Th cells is not increased by IL-4, but by IL-12 and by IL-23 instead. Consequently, ICOS expression during IL-12-driven Th1 cell polarization was transiently increased compared with the levels on Th0 cells and IL-4-driven Th2 cells. Addition of IL-12 and/or IL-23 during restimulation increased ICOS expression to the same extent on pre-established Th1, Th2, and Th0 cells, indicating that ICOS levels are not stably imposed by prior polarization. In contrast to the findings in the mouse, IL-4 significantly suppressed the ICOS-enhancing effects of IL-12 and IL-23. The functional consequence of variable ICOS levels was shown in coculture experiments with cells expressing the ICOS-ligand B7-related protein 1 (either transfected Chinese hamster ovary cells or autologous dendritic cells). Ligation of ICOS on 2-day-preactivated effector cells increased their cytokine production to an extent proportional to their ICOS expression levels. As the ICOS-enhancing potentials of IL-12 and IL-23 were maintained for several days after stimulation, both on Th1 and Th2 cells, we propose the concept that local regulation of ICOS expression on activated Th cells by IL-12 and/or IL-23 may provide a powerful means to amplify effector T cell responses in peripheral tissues, independently of the polarized state of the Th cells.


Longitudinal study of melanocytic nevi in adolescents.
Although melanocytic nevi are the strongest known risk factors for melanoma, their etiology is not well understood. This study was performed to assess the roles of constitutional pigmentary factors and sun exposure in the development of new nevi in adolescents. A cohort of 111 school children, aged 12 and 13 years at baseline, were followed up for 5 years. Whole-body counts of nevi of all sizes and detailed sun exposure histories were updated each year. Analyses of full-body nevus counts and of nevus counts on the face and neck region and on the shoulder and back region were undertaken by means of log-linear regression, allowing for repeated measures. Mean whole-body nevus counts were 130.1 (SD = 69.9) in 1990 and 215.5 (SD = 127.1) in 1994. Shoulder and back counts were consistently higher than face and neck counts. Subjects with heavy shoulder freckling had increased nevus counts on all sites investigated, with a means ratio for whole-body counts of 1.11 (95% CI, 1.03-1.19), compared with those with no freckling. Those who spent all of their school lunch times in the midday sun had a means ratio of 1.62 (95% CI, 1.15-2.29) compared with those who spent very little time in the sun during the lunch period. Summer holiday sun exposure was not significantly associated with development of nevi in this adolescent cohort. The degree of freckling, especially on the shoulders, and habitual midday sun exposure, rather than holiday sun exposure, are significant determinants of melanocytic nevi in Queensland adolescents.


Persistent alterations to enteric neural signaling in the guinea pig colon following the resolution of colitis.
Functional changes induced by inflammation persist following recovery from the inflammatory response, but the mechanisms underlying these changes are not well understood. Our aim was to investigate whether the excitability and synaptic properties of submucosal neurons remained altered 8 wk post-trinitrobenzene sulfonic acid (TNBS) treatment and to determine whether these changes were accompanied by alterations in secretory function in submucosal preparations voltage clamped in Ussing chambers. Mucosal serotonin (5-HT) release measurements and 5-HT reuptake transporter (SERT) immunohistochemistry were also performed. Eight weeks after TNBS treatment, colonic inflammation resolved, as assessed macroscopically and by myeloperoxidase assay. However, fast excitatory postsynaptic potential (fEPSP) amplitude was significantly increased in submucosal S neurons from previously inflamed colons relative to those in control tissue. In addition, fEPSPs from previously inflamed colons had a hexamethonium-insensitive component that was not evident in age-matched controls. AH neurons were hyperexcitable, had shorter action potential durations, and decreased afterhyperpolarization 8 wk following TNBS adminstration. Neuronally mediated colonic secretory function was significantly reduced after TNBS treatment, although epithelial cell signaling, as measured by responsiveness to both forskolin and bethanecol in the presence of tetrodotoxin, was comparable with control tissue. 5-HT levels and SERT immunoreactivity were comparable to controls 8 wk after the induction of inflammation, but there was an increase in glucagon-like peptide 2-immunoreactive L cells. In conclusion, sustained alterations in enteric neural signaling occur following the resolution of colitis, which are accompanied by functional changes in the absence of active inflammation.


Significance of incongruent DNA loci in the taxonomy of wood-decaying Basidioradulum radula.
Modern taxonomic studies of Agaricomycetes rely on the integrative analyses of morphology, environmental data, geographic distribution, and usually several DNA loci. However, sampling and selection of DNA loci for the analyses are commonly shallow. In this study, we suggest minimal numbers of necessary specimens to sample and DNA loci to analyze in order to prevent inadequate taxonomic decisions in species groups with minor morphological and genealogical differences. We sampled four unlinked nuclear DNA gene regions (nuc rDNA ITS1-5.8S-ITS2, gh63, rpb2, and tef1) to revise the systematics of a common wood-decaying species Basidioradulum radula (Hymenochaetales) on an intercontinental set of specimens collected in the Northern Hemisphere. The DNA loci analyzed violate the genealogical concordance phylogenetic species recognition principles, thus confirming a single-species interpretation. We conclude that Hyphodontia syringae is a younger synonym of B. radula.


[Aneurysm of the membranous portion of the interventricular septum].
The membranous portion of the interventricular septum represents the final phase of the ventricular growth. It is situated between the orifice of the coronary sinus and the supraventricular crest; immediately below the right aortic semilunar valves and not the coronary. Four cases of aneurism of the membranous portion of the interventricular septum are presented; in two, the diagnosis was made by angiocardiography study and in the rest it was made with the findings of an autopsy. All were of the female sex. Two patients presented a systolic murmur in the low mesocardia; three had heart failure, two of which were secondary to an arteriovenous short circuit through an interventricular communication, and the other due to alternations in the automatism and in the atrioventricular circulation. One case had W-P-W, type A and during its evolution presented paroxysms of atrial fibrillation and flutter, variable degrees of atrioventricular block with Stokes-Adams syndrome and ventricular fibrillation. In one case an obstruction at the level of the outflow tract of the right ventricle was suspected through phonocardiographic studies, and was confirmed subsequently with hemodynamic study. This same case presented a protosystolic aortic snap, at 0.13-0.14 sec. of the q wave of the electrocardiogram, described as of value for the diagnosis of this malformation. In two cases the angiocardiographic study showed the presence of the aneurism in the membranous portion of the interventricular septum, in one, it was visualized in the posterioanterior projection and in another in the lateral. One of the specimens had the aneurism adhered to the tricuspid septal valve, and also a fissure which communicated the left ventricle with the right atrium. In the other, the aneurismal sac was located below the septal valve of the tricuspid, producing a distortion in the anatomical architecture of the atrioventricular orifice.


Development of the community nurse in learning disability: 1.
Many accounts have described the role of the community nurse in learning disability and the nature and purpose of intervention in this situation. This article, the first in a two-part series, discusses the development of community nursing education and the need for more research.


Elevated Cerebrospinal Fluid Sodium and Chloride Levels in a Saltwater Drowning Death.
To ascribe a cause of death from drowning in a body immersed in water can be difficult because of the absence of specific postmortem findings and unreliable ancillary tests. Postmortem vitreous biochemical analysis is documented to be a useful adjunct ancillary test to aid the diagnosis of saltwater drowning. A major confounding factor in using postmortem vitreous is the effect of electrolyte diffusion and water osmosis during immersion. A recent animal study suggested that cerebrospinal fluid (CSF) biochemical analysis, which is unaffected by immersion, may be an alternative. However, to date, there are no human data to support this. We report a saltwater drowning death from presumed suicide in which the postmortem CSF sodium and chloride level was elevated compared with nonimmersion deaths. This case gives evidence to support the potential use of postmortem CSF sodium and chloride level as an adjunct to the diagnosis of saltwater drowning.


[Therapy of hepatitis B virus infection].
In the last years there was a continuous improvement in the therapy of hepatitis B virus infection. Meanwhile different therapeutic options are available. Therefore the indication for the different treatment options can be chosen dependent on clinical, biochemical, virological and histological parameters. Therapy with interferon alpha or PEG-interferon alpha should be started if positive prognostic parameters and lack of contraindications are present in a patient. Especially therapy with PEG-interferon alpha in recent studies showed good response rates. As an alternative nucleosides/nucleotides like lamivudine, adefovir or entecavir are available. During lamivudine therapy there is an increased risk for the selection of resistant strains, while the selection of resistant strains is less frequent during the medication of adefovir or entecavir. However at present the end of treatment for all nucleosides/nucleotides--especially in HBeAg negative patients--is not clearly defined. In patients with liver cirrhosis (Child B and C) only nucleos(t)ides should be used. In the future combination therapy for the treatment of chronic HBV infection seems very attractive. However at present combination therapy is not approved yet and therefore these options should only be used in clinical studies. Especially, as it seems possible that synergistic, but also antagonistic effects may exist between different drugs.


Diabetes and HIV: current understanding and future perspectives.
Diabetes mellitus is a chronic disease with a higher risk of associated infections. HIV infection severely affects diabetic patients and acts as a significant health concern. Highly active antiretroviral therapy (HAART) has changed HIV from an acute infection to a chronic infection with associated significant metabolic abnormalities such as insulin resistance, impaired glucose tolerance, metabolic syndrome, diabetes, dyslipidemia, obesity, and lipodystrophy. These metabolic disturbances add complexity to the standards of care in HIV infection and further increase the risk for cardiovascular disease and renal complications. The co-association of diabetes and HIV needs to be managed appropriately to prevent mortality and morbidity and improve patient outcome. The current understanding of diabetes and other metabolic abnormalities along with management strategies in HIV infected patients are summarized in this article. The review also focuses on recent challenges in the diagnosis and management of co-existent diabetes and HIV infection.


The Spanish flu in Denmark.
The spread of H5N1 influenza and the similarity between this avian virus and the Spanish flu virus causes fear of a new influenza pandemic, but data from the Spanish flu may also be of guidance in planning for preventive measures. Using data on influenza cases, influenza deaths and total deaths for Denmark and for Danish towns from 1917 to 1921, and population data from the 1916 and 1921 censuses, we analysed incident cases, cumulative, age-specific and age-standardized rates. Overall, more than 900,000 persons contracted flu during the y 1918-1920, and 1 out of 50 patients died from the disease. An early wave of the flu occurred in the capital and major towns, but not in peripheral towns. Influenza incidence in 1918 peaked at age 5-15 y, closely followed by the age groups 1-5 y and 15-65 y, but the influenza mortality was highest in the age groups 0-1 y and 15-65 y, with a peak mortality at age 20-34 y producing a W curve for mortality by age. The background for the better outcome in children aged 1-15 y as well as for the disease immunity in the elderly population should be further investigated.


Automatic alignment for New Englishes: Applying state-of-the-art aligners to Trinidadian English.
While forced alignment has become an essential part of data processing in phonetic research, state-of-the-art aligners are often exclusively tailor-made for majority dialects, such as American English(es). This paper provides the first in-depth investigation into the reliability of popular pre-trained aligners in New Englishes-the nativized, postcolonial Englishes spoken world-wide. Using manually aligned data from Trinidadian English, the paper examines popular aligners [Forced Alignment and Vowel Extraction (FAVE), Munich Automatic Segmentation (MAUS), and the Montreal Forced Aligner (MFA)] and their performances in automatically segmenting Trinidadian speech. Results show that, first, only specific aligners (FAVE and MFA) can provide alignment that is comparable to that in the training varieties and, to a smaller degree, general human inter-rater uncertainty. Second, even well-performing aligners introduce bias toward their training varieties: the aligners systematically produce more erroneous alignments of Trinidadian English-specific vowels, for which they have no acoustic models. The findings suggest that phonetic research on New Englishes can benefit from pre-trained, state-of-the-art aligners, but that further manual data processing may generally be required to minimize errors in the analysis of non-majority dialect data.


Differential isotopic mass splitting as a mass spectrometric tool for identifying protease substrates.
A method is described whereby stable isotopic signatures were partially incorporated into both termini of a peptide sequence giving rise to a characteristic cluster of four peaks in the mass spectral analysis. Cleavage of this peptide by a protease between the labeled positions generates two fragments both displaying their own individual signature peaks. The event of protease cleavage of the peptide was monitored by the changes in clusters within the spectrum. We believe that this technique could be used to aid the discovery of new cleavage substrates for proteases. Additionally, the analysis can be automated with dedicated software designed to select and interpret the data since all peaks of interest contain predefined signatures and can be easily distinguished from background noise.


[Predictive value of ultrasonic diaphragm thickening fraction on successful weaning for patients with myasthenia gravis crisis].
To confirm the predictive value of diaphragm thickening fraction (DTF) on successful weaning by bedside ultrasound in patients with myasthenia gravis crisis. A prospective study was conducted. The patients with myasthenia gravis crisis undergoing mechanical ventilation admitted to Department of Critical Care Medicine of the Affiliated Hospital of Qingdao University from March 2015 to February 2017 were enrolled. All patients underwent a low level pressure support mode of spontaneous breathing test (SBT), and rapid shallow breathing index (RSBI) was recorded. The indicators of right diaphragm thickness at the end of inspiration (DTei) and expiration (DTee) were determined by bedside ultrasound at 5 minutes and 60 minutes of SBT, and DTF was calculated, the changes in above parameters were observed during SBT. The patients were divided into successful weaning group and failure weaning group, and the differences in above indexes were compared between the two groups. Receiver operating characteristic curve (ROC) was used to evaluate the predictive value of DTF and RSBI at 60 minutes of SBT on successful weaning. A total of 37 patients were enrolled in the study. Ultrasonic measurement data of 63 person-times at 5 minutes of SBT and 50 at 60 minutes of SBT were obtained. There were no statistical differences in RSBI, DTei, DTee, and DTF at 5 minutes of SBT between successful weaning group (n = 33) and failure weaning group (n = 30). At 60 minutes of SBT, compared with successful weaning group (n = 33), the patients in failure weaning group (n = 17) had a higher RSBI (times×min-1×L-1: 80.41±29.08 vs. 63.94±23.84, t = 2.146, P = 0.037), and lower DTee, DTei and DTF [DTee (mm): 22.00±6.25 vs. 25.45±4.99, t = 2.127, P = 0.039; DTei (mm): 27.94±6.19 vs. 38.48±6.15, t = 5.731, P = 0.000; DTF: (24.46±14.11)% vs. (62.04±30.21)%, t = 4.845, P = 0.000]. There were no statistical differences in RSBI, DTei, DTee, and DTF between 5 minutes and 60 minutes of SBT in 33 person-time successful weaning (all P > 0.05). In 17 person who had 60 minutes of SBT but failed weaning, the RSBI at 60 minutes of SBT was significantly higher than that at 5 minutes (times×min-1×L-1: 80.41±29.08 vs. 57.29±22.46, t = 2.400, P = 0.029), and DTei and DTF were significantly decreased [DTei (mm): 27.94±6.19 vs. 35.35±6.84, t = 3.024, P = 0.000; DTF: (24.46±14.11)% vs. (61.89±23.97)%, t = 5.810, P = 0.000], but the change of DTee during SBT showed no statistical significance. ROC curve analysis showed that the area under ROC curve (AUC) of DTF at 60 minutes of SBT for predicting successful weaning was 0.898; when DTF ≥ 27.9% as the cut-off point, the sensitivity was 93.9%, specificity was 70.6%. The AUC of RSBI for predicting successful weaning was 0.669; when RSBI ≥ 86.50 times×min-1×L-1 as the cut-off point, the sensitivity was 81.8%, specificity was 52.9%. DTF at 60 minutes of SBT is the effective index of successful weaning prediction in mechanical ventilation patients with myasthenia gravis crisis.


Targeting apoptosis pathways in infections.
The programmed cell death pathway of apoptosis is essential for mammalian development and immunity as it eliminates unwanted and dangerous cells. As part of the cellular immune response, apoptosis removes the replicative niche of intracellular pathogens and enables the resolution of infections. To subvert apoptosis, pathogens have evolved a diverse range of mechanisms. In some circumstances, however, pathogens express effector molecules that induce apoptotic cell death. In this review, we focus on selected host-pathogen interactions that affect apoptotic pathways. We discuss how pathogens control the fate of host cells and how this determines the outcome of infections. Finally, small molecule inhibitors that activate apoptosis in cancer cells can also induce apoptotic cell death of infected cells. This suggests that targeting host death factors to kill infected cells is a potential therapeutic option to treat infectious diseases.


[Septic shock in a Tunisian intensive care unit: mortality and predictive factors. 100 cases].
This is a retrospective study, of 100 consecutive patients with septic shock hospitalized in the ICU of Mongi Slim Hospital La Marsa between January 1997 and December 2001. The state of shock was defined according to the criteria established by the American College of Chest physicians in conjunction with the Society of Critical Care Medicine during the consensus conference on sepsis. Our study shows that septic shock affect both sexes in the same way, that it increases with the age and with the existence of underlying diseases. The global mortality was 82%. According to our study o, septic shock mortality in creases with age and with the existence of an underling pathological condition such as high blood pressure. It also increases with the cause of the septic shock. (Pleuro-pulmonary).


Decrease of platelet serotonin content in ovariectomized female rats.
Platelet serotonin (5-HT) concentration was determined in ovariectomized and sham-operated rats by high-pressure liquid chromatography. A 23% decrease in platelet 5-HT levels was found in ovariectomized rats. Platelet 5-HT uptake mechanism was studied by incubating platelet-rich plasma with increasing concentrations of [3H]-5-HT at 37 C and 4 C for 10 sec. Kinetics parameters (Km, Vmax) characterizing active 5-HT uptake were found to be identical in both groups of rats. In vitro preincubation of platelets with 17 beta-estradiol and progesterone did not modify the 5-HT uptake levels. The platelet 5-HT decrease observed in ovariectomized rats may reflect a physiological modulation of peripheral 5-HT metabolism by ovarian hormones, which is not linked to a modification of the membranal uptake mechanism.


Integration of data and management tools into the new york state medicaid managed care encounter data system.
The New York State Department of Health has created a data warehouse to analyze and evaluate the Medicaid managed care program. Online query tools and reports, grouping tools such as Diagnostic Related Groups, and measurement tools such as Health Plan Data and Information Set (HEDIS) measures have been incorporated into the data warehouse. Other public health data sets including birth certificate data have also been integrated. The result is a powerful data set that can analyze information quickly and efficiently, with built-in data intelligence. Developed over time, this system can provide states, health insurance companies, and health data consortiums a roadmap on how to implement an integrated data warehouse solution.


DNA nano-carrier for repeatable capture and release of biomolecules.
DNA can be manipulated to design nano-machines through specific sequence recognition. We report a switchable DNA carrier for repeatable capture and release of a single stranded DNA. The activity of the carrier was regulated by the interactions among a double-stranded actuator, single stranded target, fuel, and anti-fuel DNA strands. Inosine was used to maintain a stable triple-stranded complex when the actuator's conformation was switched between open (capture) and closed (release) configurations. Time lapse fluorescence measurements show repeatable capture and release of target strands. TEM images also show visible capture of target DNA strands when gold nanoparticles were attached to the DNA carrier and the target DNA strand. The carrier activity was controlled by length of toeholds, number of mismatches, and inosine substitutions. Significantly, unlike in previously published work that reported the devices functioned only when there is a perfect match between the interacting DNA strands, the present device works only when there are mismatches in the fuel strand and the best performance is achieved for 1-3 mismatches. The device was used to successfully capture and release gold nanoparticles when linked to the target single-stranded DNA. In general, this type of devices can be used for transport and delivery of theranostic molecules.


The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision.
We have previously demonstrated that the minimum alveolar concentration of isoflurane at 1 atm that is required to prevent movement in 50% of patients or animals exposed to a maximal noxious stimulus is markedly reduced by increasing fentanyl concentrations. Total intravenous anesthesia with propofol is increasing in popularity, yet the propofol concentrations required for total intravenous anesthesia or the interaction between propofol and fentanyl have not yet been defined. Propofol and fentanyl were administered via computer-assisted continuous infusion to provide pseudo-steady-state concentrations and allow equilibration between plasma-blood concentration and their biophase concentration. For the induction of anesthesia patients were randomly allocated to receive propofol only or propofol plus fentanyl 0.2, 0.8, 1.5, 3.0, and 4.5 ng/ml. In each group patients were randomized to target propofol concentrations of 1.5-10 micrograms/ml. At 7 and 10 min arterial blood samples were taken for subsequent measurement of propofol and fentanyl concentrations. At 10 min loss of consciousness was assessed by the patients' ability to respond to a simple verbal command. Thereafter a new target concentration of propofol was entered to ensure loss of consciousness, and succinylcholine was administered to facilitate tracheal intubation. Patients were rerandomized to a new target concentration of propofol (1-19 micrograms/ml) until skin incision. Before skin incision and 1 min after skin incision, arterial blood samples were again obtained for subsequent measurement of fentanyl and propofol concentrations. At skin incision and for 1 min the patient was observed for purposeful movement. Only samples in which the pre- and poststimulus drug concentrations were within 35% of each other were included. The propofol blood concentration at which 50% or 95% of patients did not respond to verbal command (Cp50s and Cp95s, respectively) and to skin incision (Cp50i and Cp95i, respectively), were calculated by logistic regression. There were 56 evaluable patients for calculating the propofol Cp50s and 53 patients for calculating the propofol Cp50i. For propofol alone the Cp50s was 3.3 micrograms/ml and the Cp95s 5.4 microgram/ml. Increasing fentanyl concentrations reduced the Cp50s (P = 0.03), and increasing age decreased the Cp50s (P = 0.04). For propofol alone the Cp50i was 15.2 (95% confidence interval 7.6-22.8) micrograms/ml and the Cp95i 27.4 micrograms/ml. Increasing fentanyl concentrations markedly reduced the Cp50i (P < 0.01), with a 50% reduction in Cp50i produced by 0.63 ng/ml fentanyl. The propofol Cp50i was decreased by 63% with 1 ng/ml fentanyl and 89% by 3 ng/ml fentanyl. At higher fentanyl concentrations the decrease in Cp50i was proportionally less, demonstrating a ceiling effect. We defined the propofol concentration required for loss of consciousness and showed that it is reduced by increasing fentanyl concentration and by increasing age. The propofol concentration (alone) adequate for skin incision is high but is markedly reduced by fentanyl. A ceiling effect in the Cp50i for propofol is seen with fentanyl concentrations greater than 3 ng/ml.


[Determination of the distribution of ventilation-perfusion ratios: technic of elimination of multiple inert gases].
The multiple inert gas elimination technique (MIGT) facilitates the estimation of the distributions of ventilation-perfusion (VA/Q) ratios in the experimental and clinical setting. The most relevant technical aspects and equipment and operational requirements needed to measure a mixture of inert gases in both the gas phase and the blood phase using gas chromatography are overviewed with detail. Results obtained in 3 dogs and 4 syringe-homogeneous lung models were entirely consistent with data formerly reported in the literature. Particular attention is paid to the linearity of the gas chromatograph detectors, reproducibility of inert gases sampling, and analysis of brands of heparin to detect acetone content. The errors of measurement (coefficients of variation) in blood were: 1.4 for sulfur hexafluoride; 1.8% for ethane; 2% for cyclopropane and halothane, each; 2.4% for diethyl ether; and, 3.6% for acetone. Important practical points are also emphasized in order to draw attention to potential problems and issues that should be concentrated upon to minimize the error in the measurements. It is concluded that the setting up of the MIGT is well established and validated.


High phenylalanine levels directly affect mood and sustained attention in adults with phenylketonuria: a randomised, double-blind, placebo-controlled, crossover trial.
The main debate in the treatment of Phenylketonuria (PKU) is whether adult patients need the strict phenylalanine (Phe)-restricted diet. Physicians and patients lack evidence-based guidelines to help them make well-informed choices. We have carried out the first randomised double-blind placebo-controlled trial into the effects of short-term elevation of Phe levels on neuropsychological functions and mood of adults with PKU. Nine continuously treated adults with PKU underwent two 4-week supplementation periods: one with Phe, mimicking normal dietary intake, and one with placebo in randomly allocated order via a randomisation coding list in a double-blind cross-over design. A set of neuropsychological tests (Amsterdam Neuropsychological Tasks) was administered at the end of each study period. In addition, patients and for each patient a friend or relative, completed weekly Profile of Mood States (POMS) questionnaires, evaluating the patients' mood. Phe levels were measured twice weekly. Mean plasma Phe levels were significantly higher during Phe supplementation compared with placebo (p = 0.008). Neuropsychological tests demonstrated an impairment in sustained attention during Phe supplementation (p = 0.029). Both patients and their friend or relative reported lower scores on the POMS questionnaires during Phe supplementation (p = 0.017 and p = 0.040, respectively). High plasma Phe levels have a direct negative effect on both sustained attention and on mood in adult patients with PKU. A Phe-restricted "diet for life" might be an advisable option for many.


Shifts in Leukocyte Counts Drive the Differential Expression of Transcriptional Stroke Biomarkers in Whole Blood.
Our group recently identified a panel of ten genes whose RNA expression levels in whole blood have utility for detection of stroke. The purpose of this study was to determine the mechanisms by which these genes become differentially expressed during stroke pathology. First, we assessed the transcriptional distribution of the ten genes across the peripheral immune system by measuring their expression levels on isolated neutrophils, monocytes, B-lymphocytes, CD-4+ T-lymphocytes, CD-8+ T-lymphocytes, and NK-cells generated from the blood of healthy donors (n = 3). Then, we examined the relationship between the whole-blood expression levels of the ten genes and white blood cell counts in a cohort of acute ischemic stroke patients (n = 36) and acute stroke mimics (n = 15) recruited at emergency department admission. All ten genes displayed strong patterns of lineage-specific expression in our analysis of isolated leukocytes, and their whole-blood expression levels were correlated with white blood cell differential across the total patient population, suggesting that many of them are likely differentially expressed in whole blood during stroke as an artifact of stroke-induced shifts in leukocyte counts. Specifically, factor analysis inferred that over 50% of the collective variance in their whole-blood expression levels across the patient population was driven by underlying variance in white blood cell counts alone. However, the cumulative expression levels of the ten genes displayed a superior ability to discriminate between stroke patients and stroke mimics relative to white blood cell differential, suggesting that additional less prominent factors influence their expression levels which add to their diagnostic utility. These findings not only provide insight regarding this particular panel of ten genes, but also into the results of prior stroke transcriptomics studies performed in whole blood.


Neuroanatomical changes extend beyond striatal atrophy in X-linked dystonia parkinsonism.
X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative adult-onset basal ganglia model disease associated with severe striatal atrophy. Anatomical changes exceeding striatal pathology were not yet described in XDP. The present study aimed to assess the microstructure of white matter tracts in XDP using magnetic resonance tomography. Diffusion-weighted imaging was done in 10 XDP patients, aged 42.2 years (SD 8.1), and 14 ethnicity and age-matched controls, aged 40.2 years (SD 6.4). Based on diffusion tensor images, mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated. Except for in the occipital lobe, XDP patients showed generally increased MD values across the entire white matter. FA map analysis identified four significant clusters with controls showing higher FA values than XDP patients. Involved regions included the fornix, anterior thalamic radiation, corticospinal tract, and superior corona radiata bilaterally. In the fornix and the anterior thalamic radiation, the UPDRSIII total score showed a negative correlation with mean FA values at a trend level (tau = -0.40, p = 0.053). Volumetric analysis revealed significant gray matter volume loss of putamen (F(1,19) = 44.2, p < 0.001), caudate nucleus (F(1,19) = 54.3, p < 0.001), and pallidum (F(1,19) = 8.9, p = 0.007). The present study confirms striatal atrophy in XDP and provides evidence for a strong involvement of the white matter and the pallidum. This calls into question the previously held concept of exclusive striatal atrophy in this unique movement disorder. The spared occipital region may point towards a lack of anatomical connections with the atrophied striatum.


The noninvasive assessment of myocardial viability.
The major objective of noninvasive imaging for detection of myocardial viability is to assist in the improved selection of patients with coronary artery disease and severe left ventricular dysfunction who would benefit most from revascularization. The techniques most commonly used to identify viable myocardium are thallium-201 (201Tl) scintigraphy, positron emission tomography (PET) using a flow tracer in combination with a metabolic tracer, technetium-99m (99mTc) sestamibi imaging, and dobutamine echocardiography. On stress 201Tl scintigraphy, asynergic regions showing normal thallium uptake, an initial defect with delayed redistribution at 3-4 h, late redistribution at 24 h, or defect reversibility after reinjection of a second dose of 201Tl at rest all suggest preserved viability. The greater the final uptake of 201Tl in areas of regional myocardial dysfunction preoperatively, the greater the improvement in ejection fraction after coronary revascularization. Demonstration of uptake of fluoro-18 deoxyglucose (FDG) in regions of diminished blood flow on PET imaging also correlates well with improved systolic function after revascularization. 99mTc sestamibi may also be useful for assessment of myocardial viability, particularly after thrombolytic therapy for acute myocardial infarction. Dobutamine echocardiography has good positive predictive value for viability determination, but absence of systolic thickening in an akinetic zone in response to intravenous infusion of the drug may still be associated with viable myocardium in 25-50% of segments. Of all the techniques cited above, quantitative resting 201Tl scintigraphy may be the best approach for distinguishing between viable and irreversibly injured myocardium.


[Reiter's syndrome and urinary infection in a case of AIDS].
Herein we describe a case of Reiter's syndrome coexisting with HIV infection in a female parenteral drug addict who was also predisposed to multiple genitourinary involvement. In our view. the manifestation of additional autoimmune states could herald the worsening of the prognosis of HIV infection and the nephrological and urological course of these patients.


Exploiting heterozygosity in industrial yeasts to create new and improved baker's yeasts.
The main aim of the work was to utilize heterozygosity of industrial yeast strains to construct new baker's yeast strains. Commercial baker's yeast strain ALKO 743, its more ethanol tolerant descendant ALKO 554 selected initially for growth over 300 generations in increasing ethanol concentrations in a glucose medium, and ALKO 3460 from an old domestic sour dough starter were used as starting strains. Isolated meiotic segregants of the strains were characterized genetically for sporulation ability and mating type, and the ploidy was determined physically. Heterozygosity of the segregant strains was estimated by a variety of molecular characterizations and fermentation and growth assays. The results showed wide heterozygosity and that the segregants were clustered into subgroups. This clustering was used for choosing distantly or closely related partners for strain construction crosses. Intrastrain hybrids made with segregants of ALKO 743 showed 16-24% hybrid vigour or heterosis. Interstrain hybrids with segregants of ALKO 743 and ALKO 3460 showed a wide variety of characteristics but also clear heterosis of 27-31% effects as assayed by lean and sugar dough raising. Distiller's yeast ALKO 554 turned out to be a diploid genetic segregant and not just a more ethanol tolerant mutant of the tetraploid parent strain ALKO 743.


Mammographic screening and disease presentation of breast cancer patients who die of disease.
This retrospective study assesses the presentation of breast cancer patients who died of disease. The goal was to estimate the proportion of patients whose cancer was detected by a screening mammogram, yet still proved fatal, and to characterize contemporary fatal breast cancers. Patients who died of breast cancer between 1995 and 2001 and were treated at three hospitals with complete, accessible information were identified using the Rhode Island Department of Health database and State Cancer Registry. Patients were classified as routinely screened, true interval, off-program, or unscreened. The median maximum diameter of fatal cancers was 2.5 cm. Sixty-nine percent of patients had lymph node metastases and 19% had stage IV disease. Fifty-seven percent were unscreened and 12% were routinely screened, with 2.5 cm and 1.5 cm median tumor diameters, respectively. Fifty-two percent of unscreened patients and no routinely screened patients had stage III or IV disease. Fifteen percent of fatal cancers were interval cancers. Only 27% of patients who died of breast cancer were participants in routine screening programs in Rhode Island, where 84% of women receive regular mammograms. This study complements randomized, population-based trials demonstrating a significant mortality reduction with an invitation to participate in screening.


In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency.
A large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy. In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. We used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography-tandem mass spectrometry. Relative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased by >8-fold. Our findings provide strong evidence that coexisting carnitine deficiency masks some indicators of biotin deficiency and support the potential importance of the ratios of acylcarnitines arising from the acyl-CoA substrates and products for biotin-dependent carboxylases in detecting the biotin deficiency that is masked by coexisting carnitine deficiency.


[Does the treatment of peritonitis affect residual renal function in CAPD?].
The aim of the study was a retrospective analysis of potentially negative influence of aminoglycosides on RRF in patients with peritonitis in course of CAPD program. From the group of 47 patients of our center who were treated because of peritonitis in years 1991-2000 we finally selected 11 persons with preserved RRF in whom 16 incidents of peritonitis were revealed. The mean value of RRF in this group was 1.55 (+/- 2.0) ml/min before the treatment and 1.44 (+/- 2.2) ml/mi after the treatment of peritonitis. There was no statistical difference between these values (p = 0.32). It was also revealed that in 5 cases (31%) RRF decreased after the peritonitis treatment while in 7 cases (44%) no change of RRF value was observed and in 4 cases (25%) RRF value was increased after the treatment of peritonitis. The efficacy of treatment with the standard protocol in observed group was 93.75%. On the base of performed analysis no negative influence of peritonitis therapy with aminoglycosides and I-st generation cephalosporines was observed. It was stated that aminoglycosides may still be used in peritonitis therapy under the condition that precise monitoring of RRF will be introduced.


Probable cutaneous allergic response to subcutaneous heparin--a case report.
Heparin is a heterogeneous mixture of sulfated mucopolysaccharides, commonly used injectable anticoagulant. It is known to cause cutaneous adverse reactions like eczema, erythematous plaques, exfoliative dermatitis and tissue necrosis. We report a case of probable cutaneous allergic response caused by injection of heparin with an established causality and severity. The reaction developed after stopping the drug therapy and after the patient had already been discharged. Since heparin is a widely used drug and this reaction can manifest even after the drug therapy has ceased, thorough counseling of the patient is mandatory.


A Study on the Evaluation of Polyenoic Vegetable Oils and Their Female Health Benefits Based on Time Series Analysis Model: The Case of Peony Seed Oil.
Polyenoic vegetable oils mainly contain polyenoic acids such as linoleic acid and linolenic acid, as well as active ingredients such as VE, phytosterols, mineral elements, and squalene. Among them, schisandra oil, kiwi seed oil, grape seed oil, maitake fruit oil, and evening primrose seed oil all contain up to 80% or more polyenoic acids. Studies have shown that polygenic vegetable oils have the effects of assisting in lowering blood lipids, antioxidation, delaying ageing, anti-inflammation, sun protection, moisturizing, slimming and weight loss, etc. They can be widely used in nutritional and healthy edible oils, health food, skin care, and cosmetic products and have great prospects for development and utilization. This paper explores the application of artificial neural networks in the analysis of data. A nonlinear time series prediction method based on the BP algorithm is proposed. The prediction accuracy is much higher than that of the traditional method.


A new approach to the synthesis of peptidomimetic renin inhibitors: palladium-catalyzed asymmetric allylation of acyclic alkyl aryl ketones.
A new approach to the synthesis of Tekturna, a recently marketed drug for hypertension, takes advantage of a modified protocol of the Stoltz palladium-catalyzed asymmetric allylation with a t-BuPHOX ligand for the synthesis of allylated acyclic alkyl aryl ketones. The method led to an α-isopropyl α-allyl aryl ketone in 90% yield and 88 to 91% ee, which was used in the synthesis of an advanced intermediate toward Tekturna. A beneficial effect of protic additives, such as BHT (2,6-di-tert-butyl-p-cresol), on the time and enantioselectivity of the reaction was discovered.


Controlling algal growth in photo-dependent decolorant sludge by photocatalysis.
In the treatment of synthetic dye wastewater by photosynthetic bacteria under optical irradiation, excessive algal growth and adhesion on the walls of the reactor are serious problems. The adverse effects of excessive algal growth on photosynthetic bacterial activity are significantly greater than those of the decreased optical irradiation of the solution. In this report, we investigated the effects of photocatalysis on the growth of algae (Chroococcus sp.) and photosynthetic bacteria. The different sensitivities of Chroococcus sp. and photosynthetic bacteria to photocatalysis were observed by an ATP assay. Moreover, from microscopy findings, some algae were damaged by TiO2 with UV. We suggested that some algae suffered from membrane damage and consequently cell substances were released, resulting in the increase of dissolved material following treatment using TiO2 with UV.


Need for Uniqueness Determines Reactions to Web-Based Personalized Advertising.
The presented empirical study among a sample of n = 256 participants addressed the relationship between consumers' need for uniqueness and their reactions to web-based personalized advertising. Drawing on regulatory focus theory, we argue that the consumers' need for uniqueness dimensions creative choice and similarity avoidance may relate to promotion and prevention regulatory orientations, respectively. Accordingly, we hypothesized that creative choice and similarity avoidance would differentially predict self-reported approach and avoidance behavior toward personalized advertising. These direct relationships were further expected to be mediated by subjective evaluations of personalized advertising (i.e., perceived value and irritation). In line with these hypotheses, we found that creative choice predicted approach behavior through increased web-based personalized advertising value, whereas similarity avoidance predicted avoidance behavior through increased irritation. Creative choice also predicted decreased irritation, which in turn was related to decreased approach behavior. In sum, the results suggest that the consumers' need for uniqueness dimensions should not be investigated as a composite, as they seem to reflect different regulatory orientations and are therefore likely to evoke different affective, cognitive, and behavioral responses.


In vivo technetium-99m S12 antibody imaging of platelet alpha-granules in rabbit endothelial neointimal proliferation after angioplasty.
To examine the specificity of technetium-99m monoclonal antibody (S12) imaging for identifying activated platelets at interventional injury sites in atherosclerotic rabbit arteries, subgroups of unheparinized rabbits (n = 39) underwent serial percutaneous transluminal aortic angioplasty (PTA) procedures (with or without intravascular stent placement) followed by in vivo and then ex vivo gamma camera imaging, scanning, and immunoelectron microscopy to determine the intravascular loci of S12 Fab' antibody binding. Despite angiographic vessel patency, image-derived ratios of in vivo S12 binding in injured versus uninjured vascular segments were significantly increased (p less than 0.05) after one PTA (1.3 +/- 0.17, n = 7), PTA twice at 6-week intervals (1.4 +/- 0.22, n = 7), and PTA plus stent placement (1.6 +/- 0.28, n = 7) compared with control experiments (1.1 +/- 0.13, n = 7). Ex vivo imaging of blood-free excised aortas confirmed S12 localization at PTA (2 +/- 0.4, n = 3) and PTA plus stent placement (5 +/- 3.8, n = 7) sites (both p less than 0.05 versus controls). S12 antibody uptake decreased significantly (p less than 0.05) at 1 week after PTA plus stent placement in vivo (1.1 +/- 0.10, n = 4) and ex vivo (1.6 +/- 0.7, n = 3). Electron microscopic studies confirmed dense platelet, fibrin, and red blood cell deposition in regions of acute injury, with endothelial neointimal proliferation at 1 week after PTA. Immunoelectron microscopic studies confirmed specific in vivo S12 binding (22:1 versus nonrelevant IgG) at sites of alpha-granule GMP-140 expression in activated platelets. Therefore, S12 studies may be useful to localize sites of platelet-derived mitogen release at arterial PTA injury sites.


Time in range: new parameter to evaluate blood glucose control.
Continuous glucose monitoring became more common in everyday clinical practice. New parameters have been created as a standard for assessing the degree of control for people with diabetes and can be used more clearly than glycated haemoglobin. The new parameter time in range represents a significant benefit not only for diabetologists, but also an important tool to help the patients in their daily lives with diabetes.


Crystallization and preliminary X-ray crystallographic analysis of the Bag2 amino-terminal domain from Mus musculus.
Bag2, an atypical member of the Bag family of Hsp70 co-chaperones, acts as both an Hsp70 nucleotide-exchange factor and an inhibitor of the Hsp70-binding E3 ubiquitin ligase CHIP (carboxyl-terminus of Hsp70-interacting protein). The amino-terminal domain of Bag2 (Bag2-NTD), which is required for inhibition of CHIP, has no sequence homologs in the PDB. Native and selenomethionyl (SeMet) forms of Bag2-NTD were crystallized by hanging-drop vapor diffusion. Native Bag2-NTD crystals diffracted to 2.27 Å resolution and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 75.5, b = 84.7, c = 114.1 Å. SeMet Bag2-NTD crystals diffracted to 3.10 Å resolution and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 37.2, b = 53.3, c = 86.7 Å. Phases for the SeMet Bag2-NTD crystal were solved by single-wavelength anomalous diffraction. Initial phasing and model building using the 3.10 Å resolution SeMet Bag2-NTD data set suggested that Bag2-NTD forms a dimer and adopts a fold distinct from those of any domains annotated in the Pfam or SMART domain databases.


Detection of Cytotoxic T-Lymphocyte Associated Antigen-4 Gene Polymorphism in Type 1 Diabetes Mellitus.
Type 1 diabetes is one of the most common chronic childhood illnesses. Interplay between genetic susceptibility and environmental factors is thought to provide the fundamental element for the disease. It has been shown that more than 40 genetic loci are associated with T1DM. Important one among these is the CTLA-4. This work aimed to detect Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4) gene polymorphism in patients with type 1 diabetes mellitus T1DM using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to clarify its role in the susceptibility to T1DM. The study was carried out on forty unrelated Egyptian children with TIDM. Twenty unrelated healthy children were enrolled as a control group. Blood samples were collected from patients and control groups and subjected to CTLA-4 gene polymorphism analysis using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). CTLA-4 G allele and GG homozygous genotype were significantly increased in T1DM patients than in control group (P < 0.001, P = 0.002 respectively). There was significant association between the three CTLA-4 genotypes (AA, AG, GG) and diabetic complications (p = 0.002), AG and GG polymorphisms were associated with complications of diabetes with ratio 84.6% and 100% respectively. While no association was found with sex, weight, height, risk factors of diabetes or insulin treatment. It was concluded that there is a strong association between AG polymorphism and T1DM (P = 0.002).


Dual-Responsive Micelles with Aggregation-Induced Emission Feature and Two-Photon Aborsption for Accurate Drug Delivery and Bioimaging.
Intelligent polymeric micelles provide great potential for accurate cancer theranostics. Herein, gemcitabine (GEM)-conjugated redox-responsive prodrug micelles based on a pH-responsive charge-conventional PMPC-b-P (DEMA-co-SS-GEM-co-TPMA) copolymer and a two-photon absorbing aggregation-induced emission (AIE) fluorescence probe have been developed for lysosome-targeted drug release and bioimaging. The multifunctional copolymer has been synthesized via RAFT polymerization, and GEM is conjugated to the copolymer via GSH-cleavable disulfide bonds. These GEM-conjugated micelles exhibit great pH responsiveness at pH 5.0, while being stable at pH 6.0. GSH-triggered drug release can be observed with the GSH concentration increased from 0 to 10 mM. Moreover, the high-quality AIE-active two-photon imaging is confirmed by cell and deep-tissue imaging. More importantly, the distribution of these nanocarriers can be traced because of the AIE feature of the micelles. Along with good in vitro and in vivo tumor-suppression ability and significantly reduced side effects, this smart two-photon AIE micelle would be a potential candidate for cancer diagnosis and therapy.


Diagnosing Thoracic Outlet Syndrome: Current Approaches and Future Directions.
The diagnosis of thoracic outlet syndrome (TOS) has long been a controversial and challenging one. Despite common presentations with pain in the neck and upper extremity, there are a host of presenting patterns that can vary within and between the subdivisions of neurogenic, venous, and arterial TOS. Furthermore, there is a plethora of differential diagnoses, from peripheral compressive neuropathies, to intrinsic shoulder pathologies, to pathologies at the cervical spine. Depending on the subdivision of TOS suspected, diagnostic investigations are currently of varying importance, necessitating high dependence on good history taking and clinical examination. Investigations may add weight to a diagnosis suspected on clinical grounds and suggest an optimal management strategy, but in this changing field new developments may alter the role that diagnostic investigations play. In this article, we set out to summarise the diagnostic approach in cases of suspected TOS, including the importance of history taking, clinical examination, and the role of investigations at present, and highlight the developments in this field with respect to all subtypes. In the future, we hope that novel diagnostics may be able to stratify patients according to the exact compressive mechanism and thereby suggest more specific treatments and interventions.


Survival in synucleinopathies: A prospective cohort study.
Parkinson disease (PD), multiple system atrophy (MSA), and pure autonomic failure (PAF) involve cytoplasmic deposition of α-synuclein and are considered to be synucleinopathies. Approximately 40% of patients with PD, most patients with MSA, and all patients with PAF have neurogenic orthostatic hypotension (OH). This study compared long-term survival in these synucleinopathies. In this prospective cohort study, survival data were obtained for 97.6% of 206 referred patients evaluated between 1994 and 2014 (47 PD + OH, 54 PD no OH, 15 cerebellar MSA [MSA-C], 57 parkinsonian MSA [MSA-P], 28 PAF). Individual diagnoses were confirmed by clinical criteria and results of pharmacologic, neurochemical, and neuroimaging tests of sympathetic noradrenergic innervation. The Cox proportional hazard model was used to calculate hazard ratios (HRs) from symptom onset and from time of evaluation to death. Patients with MSA-C or MSA-P had shorter survival from symptom onset than did patients with PD + OH (age- and sex-adjusted HR = 6.1, 5.6; p < 0.0001 each), PAF (HR = 10.8, 9.9; p < 0.0001 each) or PD no OH (HR = 14.9, 13.6; p < 0.0001 each). Among parkinsonian patients who died, median times from motor onset to death were 7.5 years in MSA-P, 11.6 years in PD + OH, and 15.8 years in PD no OH. Probabilities of survival for 10 years from onset of relevant symptoms were 0.39 in MSA-C, 0.33 in MSA-P, 0.74 in PD + OH, 0.87 in PAF, and 0.93 in PD no OH. In synucleinopathies, survival depends on the particular disease, with the risk of death greater in MSA-P than in PD + OH and in PD + OH than in PD no OH.


The evolving use of radioiodine therapy in differentiated thyroid cancer.
The incidence of differentiated thyroid cancer has increased worldwide over the last three decades, but thyroid cancer-related mortality remains stable. Until recently, the standard treatment for most thyroid cancers has been near-total thyroidectomy followed by radioiodine remnant ablation. Observational data support lower recurrence rates and improved survival after radioiodine ablation in patients with high-risk cancers; however, a similar benefit has not been established for all patients with thyroid cancer. Risk stratification should be used to identify patients who are likely to benefit from radioiodine ablation and guide therapeutic decisions. For most patients who need radioiodine remnant ablation, preparation for therapy with recombinant human thyroid-stimulating hormone stimulation is as effective as thyroid hormone withdrawal. Lower therapeutic doses of radioiodine are recommended for the majority of thyroid remnant ablations. Higher doses are reserved for advanced disease at initial diagnosis, local recurrences that cannot be treated with surgery alone, and distant metastatic disease.


Trends and determinants of second-pregnancy smoking among young-adult mothers who smoked during their first pregnancy.
We examined the trends and determinants of second-pregnancy smoking behavior among Michigan young-adult mothers who smoked during their first pregnancy (N = 14,731). Maternally linked Michigan birth certificate data (1989-2004) were used to identify first and second pregnancies for young-adult mothers. ZIP code data were merged with census data to proxy for median household income and population size at the ZIP code level. For first-pregnancy smokers, linear and logistic regressions were used to analyze (a) the determinants of second-pregnancy smoking and (b) the association of birth outcomes with second-pregnancy smoking. Among young adults who smoked during their first pregnancy, second-pregnancy smoking was (a) inversely related to income and population, (b) less prevalent after 1997, (c) more likely after a low-birthweight first birth, and (d) less likely after a premature first birth. Despite recent declines in second-pregnancy smoking rates among young adults who smoked during their first pregnancy, these rates remain disturbingly high (more than 70%). Future smoking cessation efforts should target mothers who have lower incomes, live in less-populated areas, and have previously had low-birthweight babies. The results suggest that higher cigarettes taxes would also further reduce recurrent smoking.