Preservation Rhinoplasty and the Crooked Nose.
Crooked or deviated noses pose a specific challenge as many of the elements in a deviated nose are not symmetric and therefore not ideal for preservation techniques. Deviated noses are often where a hybridization between preservation and structural rhinoplasty is required. Careful preoperative evaluation of the soft tissue and bony anatomy of the patient is very important and congenital or post-traumatic asymmetry may involve more than the nasal pyramid. Full exposure of the nasal pyramid allows for visualization and appropriate osteotomy or rhinosculpture.


Performance improvement in the JCAHO environment of care.
Using security management to demonstrate performance improvement for JCAHO can be a viable option. The article illustrates how a program for reducing theft became the basis for demonstrating performance improvement.


Chitosan/alginate multilayer film for controlled release of IDM on Cu/LDPE composite intrauterine devices.
To reduce such side effects as pain and bleeding caused by copper-containing intrauterine device (Cu-IUD), a novel medicated intrauterine device, which is coated with an indomethacin (IDM) delivery system on the surface of copper/low-density polyethylene (Cu/LDPE) composite intrauterine device, has been proposed and developed in the present work. The IDM delivery system is a polyelectrolyte multilayer film, which is composed of IDM containing chitosan and alginate layer by layer, is prepared by using self-assembled polyelectrolyte multilayer method, and the number of the layers of this IDM containing chitosan/alginate multilayer film can be tailored by controlling the cyclic repetition of the deposition process. After the IDM containing chitosan/alginate multilayer film is obtained on the surface of Cu/LDPE composite intrauterine device, its release behavior of both IDM and cupric ion has been studied in vitro. The results show that the release duration of IDM increase with the increasing of thickness of the IDM containing chitosan/alginate multilayer film, and the initial burst release of cupric ion cannot be found in this novel medicated Cu/LDPE composite IUD. These results can be applied to guide the design of novel medicated Cu-IUD with minimal side effects for the future clinical use.


Morphological and transcriptomic analysis revealing morphological variations and genetic clues in one Lentinula edodes abnormal browning strain.
Strain abnormal browning is a common problem during cultivation of Lentinula edodes. In this study, the L. edodes strain mycelia isolated from Le-WB and cultured on MYG (Le-WP) isolated from an abnormal browning bag was compared with its normal control mycelia isolated from Le-BB and cultured on MYG (Le-BP). The aerial hyphae of Le-WP were white, and the hyphal growth was significantly reduced. Morphological observation of Le-WP under scanning electron microscope (SEM) and transmission electron microscopy (TEM) revealed abnormal organelle structures. Through transcriptomic analysis, more differentially expressed genes (DEGs) were expressed in the metabolic process and catalytic activity in Le-WP than Le-BP. Two Kyoto encyclopedia of genes and genomes (KEGG) pathways named pentose and glucorunate interconversions, and starch and sucrose metabolism were found to be enriched in Le-WP. The gene expression profiles involved in these two pathways were further analyzed and 12 key genes were selected to be verified by quantitative real-time PCR (qRT-PCR), and the results showed that most of these genes were upregulated in Le-WP. Additionally, the content of 1,3-beta-glucan in Le-WP was also significantly higher than in other samples. This research suggests that abnormal strains may be related to the abnormal synthesis of 1,3-beta-glucan, and it needs further research. This research exhibits possible morphological and genetic clues of Le-WP and lays the foundation for understanding the degeneration of L. edodes strains.


The biological invasion of an apex predator (Silurus glanis) amplifies PCB transfer in a large lake food web.
Invasive species can affect food web structure possibly modifying the transfer of pollutants in ecosystems but this facet of biological invasion remains largely unexplored. We examined how trophic and ontogenetic characteristics of the invasive European catfish could differ from its native counterpart, the Northern pike, possibly resulting in the amplification of PCB transfer to the higher trophic levels in a large lake food web. The PCB contents of catfish and pike were on average low (Ʃ7 PCBi 42.4 ± 38.6 ng g-1 ww and 37.9 ± 49.4 ng g-1 ww respectively) and dominated by PCB153 (~35 % of the PCB contamination). Only the largest pike (126 cm) slightly exceeded the European sanitary threshold of 125 ng g-1 ww Ʃ6 PCBi-NDL. Both species increased in trophic position with body size while catfish had clearly higher littoral reliance than pike indicating they exploited complementary trophic niches. PCB biomagnification was identified only for catfish (PCB153, Ʃ7 PCBi) leading to trophic magnification factor of ~5. PCB ontogenetic bioaccumulation was pervasive for catfish (PCB101, PCB118, PCB153, PCB138 and Ʃ7 PCBi) and identified for pike only regarding PCB101. The derived size accumulation factors (~1.02) indicated a size-doubling PCB contamination of ~40 cm for catfish. This finding suggested that catfish would exceed the European sanitary threshold at body size larger than 168 cm possibly constraining their commercial exploitation. Our results highlighted that the invasive catfish was a littoral-oriented apex predator occupying an alternative trophic niche as compared to pike thereby modifying the lake food web structure that resulted in an enhancement of PCB transfer to higher trophic levels. The biomagnification and ontogenetic bioaccumulation of catfish underlined the impact of this biological invasion on the fate of PCB in the ecosystem. Finally, the remarkable inter-individual PCB contamination suggested variable inter-individual PCB exposure likely associated to localized hotspots of PCB contamination in the lake.


Laparoscopic treatment of metabolic syndrome in patients with type 2 diabetes mellitus.
Metabolic syndrome refers to risk factors for cardiovascular disease. Hyperglycemia is a critical component contributing to the predictive power of the syndrome. This study aimed to evaluate the results from the laparoscopic interposition of an ileum segment into the proximal jejunum for the treatment of metabolic syndrome in patients with type 2 diabetes mellitus and a body mass index (BMI) lower than 35. Laparoscopic procedures were performed for 60 patients (24 women and 36 men) with a mean age of 51.7 +/- 6.4 years (range, 27-66 years) and a mean BMI of 30.1 +/- 2.7 (range, 23.6-34.4). All the patients had a diagnosis of type 2 diabetes mellitus (T2DM) given at least 3 years previously and evidence of stable treatment using oral hypoglycemic agents, insulin, or both for at least 12 months. The mean duration of type 2 diabetes mellitus was 9.6 +/- 4.6 years (range, 3-22 years). Metabolic syndrome was diagnosed for all 60 patients. Arterial hypertension was diagnosed for 70% of the patients (mean number of drugs, 1.6) and hypertriglyceridemia for 70%. High-density lipoprotein was altered in 51.7% of the patients and the abdominal circumference in 68.3%. Two techniques were performed: ileal interposition (II) into the proximal jejunum and sleeve gastrectomy (II-SG) or ileal interposition associated with a diverted sleeve gastrectomy (II-DSG). The II-SG procedure was performed for 32 patients and the II-DSG procedure for 28 patients. The mean postoperative follow-up period was 7.4 months (range, 3-19 months). The mean BMI was 23.8 +/- 4.1 kg/m(2), and 52 patients (86.7%) achieved adequate glycemic control. Hypertriglyceridemia was normalized for 81.7% of the patients. An high-density lipoprotein level higher than 40 for the men and higher than 50 for the women was achieved by 90.3% of the patients. The abdominal circumference reached was less than 102 cm for the men and 88 cm for the women. Arterial hypertension was controlled in 90.5% of the patients. For the control of metabolic syndrome, II-DSG was the more effective procedure. Laparoscopic II-SG and II-DSG seem to be promising procedures for the control of the metabolic syndrome and type 2 diabetes mellitus. A longer follow-up period is needed.


Implementing music therapy on an adolescent inpatient unit: a mixed-methods evaluation of acceptability, experience of participation and perceived impact.
We aimed to assess the feasibility of delivering a music therapy program on adolescent psychiatric wards. We undertook a mixed-methods evaluation of a pilot program. Various active and receptive techniques were employed in group music therapy sessions delivered as part of a structured clinical program. Data collected in interviews with participants and staff and feedback questionnaires were thematically and descriptively analysed and triangulated. Data from 62 questionnaires returned by 43 patients who took part in 16 music therapy sessions, and seven staff, evidenced strong support for music therapy. Patients typically reported experiencing sessions as relaxing, comforting, uplifting, and empowering; >90% would participate by choice and use music therapeutically in the future. Staff endorsed music therapy as valuable therapeutically, reporting that patients engaged enthusiastically and identified sessions as improving their own moods and ward milieu. Integration of music therapy in inpatient treatment of adolescents is feasible and acceptable, and is valued by staff and patients as a complement to 'talking therapies'. Participation is enjoyed and associated with outcomes including improvement in mood, expression of feelings and social engagement consistent with recovery.


NMR-spectroscopic evidence of intermediate-dependent pathways for acetic acid formation from methane and carbon monoxide over a ZnZSM-5 zeolite catalyst.
Two ways: a Zn-modified ZSM-5 zeolite catalyst was developed for the reaction of methane with carbon monoxide to directly produce acetic acid under mild conditions (573-623 K), and two different intermediate-dependent reaction pathways were unambiguously identified for acetic acid formation by in situ solid-state NMR spectroscopy.


Facial soft tissue augmentation with Artecoll(®): A review of eight years of clinical experience in 153 patients.
Artecoll (Canderm Pharma Inc, Canada) is a semipermanent, injectable, soft tissue filler composed of uniform polymethylmethacrylate microspheres in a bovine collagen gel, which has been used in Europe over the past decade. The authors review their experience using Artecoll as an injectable material for the correction of deep static folds of the face, improvement of nasal asymmetries following rhinoplasty, depressed acne scars and augmentation of the lip. A retrospective chart review, subjective patient satisfaction feedback and objective findings noted by the senior author were performed over an eight-year period. A total of 153 patients were treated with Artecoll injections; 74 underwent lip augmentation, 21 underwent deep nasolabial fold augmentation, eight underwent glabellar fold augmentation, 26 were treated for minor nasal dorsal irregularities and 24 were treated for depressed acne scars. No early or delayed allergic responses were reported. Complications occurred most commonly with lip augmentation, in which 13.5% of patients noted significant noticeable bruising postinjection that resolved completely within one week, 51.3% had detectable implant on palpation, and 13.1% required further intervention with massage, steroid injection and/or local excision to correct for lumpiness. Sixty per cent of patients requiring further intervention responded successfully, while local excision was performed on the two patients who failed to respond after six months of massage and steroid therapy. Overall, a total of 11 patients (14.9%) had minor asymmetries or less than optimal results within the lip augmentation study group. Among other sites, the most common complaint was undercorrection of the fold or wrinkle. Based on the authors' experience, Artecoll is a safe, viable option for long-term treatment of deep facial wrinkles, nasal asymmetry, hypoplastic or atrophic lips, and depressed acne scars, and the results have been accompanied by a high degree of patient satisfaction. Although the implant is often palpable, rarely does it cause significant visible lumps. Its use and applications as a semipermanent injectable agent certainly warrant further investigation.


A genome-wide cross-trait analysis identifies genomic correlation, pleiotropic loci, and causal relationship between sex hormone-binding globulin and rheumatoid arthritis.
Our study aims to investigate an intrinsic link underlying sex hormone-binding globulin (SHBG) and rheumatoid arthritis (RA), which remains inconclusive in observational settings. Summary statistics were collected from the largest GWAS(s) on SHBG adjusted for BMI (SHBGadjBMI; Noverall = 368,929; Nmen = 180,094; Nwomen = 188,908), crude SHBG (Noverall = 370,125; Nmen = 180,726; Nwomen = 189,473), and RA (Ncase = 22,350; Ncontrol = 74,823). A genome-wide cross-trait design was performed to quantify global and local genetic correlation, identify pleiotropic loci, and infer a causal relationship. Among the overall population, a significant global genetic correlation was observed for SHBGadjBMI and RA ([Formula: see text] = 0.11, P = 1.0 × 10-4) which was further supported by local signal (1q25.2). A total of 18 independent pleiotropic SNPs were identified, of which three were highly likely causal variants and four were found to have effects on both traits through gene expression mediation. A putative causal association of SHBGadjBMI on RA was demonstrated (OR = 1.20, 95% CI = 1.01-1.43) without evidence of reverse causality (OR = 0.999, 95% CI = 0.997-1.000). Sex-specific analyses revealed distinct shared genetic regions (men: 1q32.1-q32.2 and 5p13.1; women: 1q25.2 and 22q11.21-q11.22) and diverse pleiotropic SNPs (16 in men and 18 in women, nearly half were sex-specific) underlying SHBGadjBMI and RA, demonstrating biological disparities between sexes. Replacing SHBGadjBMI with crude SHBG, a largely similar yet less significant pattern of results was observed. Our cross-trait analysis suggests an intrinsic, as well as a sex-specific, link underlying SHBG and RA, providing novel insights into disease etiology.


Photoluminescent, "ice-cream cone" like Cu-In-(Zn)-S/ZnS nanoheterostructures.
Copper based ternary and quaternary quantum confined nanostructures have attracted huge attention over recent years due to their potential applications in photonics, photovoltaics, imaging, sensing and other areas. However, anisotropic nanoheterostructures of this type are still poorly explored to date, despite numerous predictions of the distinctive optical properties of these highly fluorescent heavy metal free nanostructures. Here, we report new fluorescent multicomponent Cu-In-(Zn)-S/ZnS nanoheterostructures with a unique anisotropic "ice-cream cone" like morphology. These nanostructures have been prepared with a seeded growth technique and exhibit distinct photophysical properties with maximum emission in the visible range (≈ 640 nm) and long photoluminescence lifetimes (τaverage ≥ 300 ns). In depth time interval studies have been carried out to better understand the step by step growth mechanism of this distinct "ice-cream cone" like geometry. We have demonstrated that the crystal structure evolution from the zinc blende Cu-In-S core to the wurtzite "ice cream cone" like Cu-In-(Zn)-S/ZnS nanocrystals plays a key role in the origin of this morphology. This research opens new possibilities to produce unique fluorescent Cu-based multicomponent anisotropic heteronanostructures, while also offering a distinctive insight into the design of bespoke nanostructures, which could find a range of potential applications.


Zn-ligation in inorganic deposits in the wall of the human aorta determined by X-ray absorption spectroscopy.
X-ray absorption spectra were recorded at the K edge of Zn from inorganic deposits present in the human aortic wall. The interatomic distances and coordination numbers obtained indicate that Zn atoms probably occupy selected Ca positions in the lattice of the octacalcium phosphate crystals localized at the surface of the deposit.


Excitant amino acids and audiogenic seizures in the genetically epilepsy-prone rat. II. Efferent seizure propagating pathway.
Previous studies indicate that the inferior colliculus is the brain stem auditory nucleus most sensitive to the chemical blockade of audiogenic seizures in the genetically epilepsy-prone rat. Other auditory structures do not appear to be as important. This study attempted to define the efferent pathways involved in propagation of the seizure from the colliculus to the spinal cord where the motor components of the convulsion are generated. This study also determined whether certain nuclei which have been implicated in the propagation of seizures in other epilepsy models are involved in audiogenic seizures. The excitant amino acid antagonist, 2-amino-7-phosphonoheptanoate, was infused bilaterally into several of those sites. The drug was effective in significantly reducing seizure severity with infusion of 5 nmol bilaterally into the midbrain and the pontine reticular formation or the substantia nigra. However, similar drug doses were not effective when infused into the entopeduncular nucleus even though prominent behavioral effects were observed with this infusion. Infusion of 2-amino-7-phosphonoheptanoate into the prepiriform cortex resulted in a small but significant reduction in seizure severity. These results suggest that inhibition of excitatory transmission within the substantia nigra and the reticular formation effectively blocks the output pathway for the audiogenic seizures, whereas the role of the prepiriform cortex in this process is relatively minor.


Implications of the COVID-19 Pandemic for Cardiovascular Disease and Risk-Factor Management.
COVID-19 and our public health responses to the pandemic may have far-reaching implications for cardiovascular (CV) risk, affecting the general population and not only survivors of COVID-19. In this narrative review, we discuss how the pandemic may affect general CV risk for years to come and explore the mitigating potential of telehealth interventions. From a health care perspective, the shift away from in-person office visits may have led many to defer routine risk- factor management and may have had unforeseen effects on continuity of care and adherence. Fear of COVID-19 has led some patients to forego care for acute CV events. Curtailment of routine outpatient laboratory testing has likely delayed intensification of risk-factor-modifying medical therapy, and drug shortages and misinformation may have negative impacts on adherence to antihypertensive, glucose-lowering, and lipid-lowering agents. From a societal perspective, the unprecedented curtailment of social and economic activities has led to loss of income, unemployment, social isolation, decreased physical activity, and increased frequency of depression and anxiety, all of which are known to be associated with worse CV risk-factor control and outcomes. We must embrace and evaluate measures to mitigate these potential harms to avoid an epidemic of CV morbidity and mortality in the coming years that could dwarf the initial health effects of COVID-19.


Dispensability of the [4Fe-4S] cluster in novel homologues of adenine glycosylase MutY.
7,8-Dihydro-8-deoxyguanine (8oG) is one of the most common oxidative lesions in DNA. DNA polymerases misincorporate an adenine across from this lesion. Thus, 8oG is a highly mutagenic lesion responsible for G:C→T:A transversions. MutY is an adenine glycosylase, part of the base excision repair pathway that removes adenines, when mispaired with 8oG or guanine. Its catalytic domain includes a [4Fe-4S] cluster motif coordinated by cysteinyl ligands. When this cluster is absent, MutY activity is depleted and several studies concluded that the [4Fe-4S] cluster motif is an indispensable component for DNA binding, substrate recognition and enzymatic activity. In the present study, we identified 46 MutY homologues that lack the canonical cysteinyl ligands, suggesting an absence of the [4Fe-4S] cluster. A phylogenetic analysis groups these novel MutYs into two different clades. One clade is exclusive of the order Lactobacillales and another clade has a mixed composition of anaerobic and microaerophilic bacteria and species from the protozoan genus Entamoeba. Structural modeling and sequence analysis suggests that the loss of the [4Fe-4S] cluster is compensated by a convergent solution in which bulky amino acids substitute the [4Fe-4S] cluster. We functionally characterized MutYs from Lactobacillus brevis and Entamoeba histolytica as representative members from each clade and found that both enzymes are active adenine glycosylases. Furthermore, chimeric glycosylases, in which the [4Fe-4S] cluster of Escherichia coli MutY is replaced by the corresponding amino acids of LbY and EhY, are also active. Our data indicates that the [4Fe-4S] cluster plays a structural role in MutYs and evidences the existence of alternative functional solutions in nature.


Boron Doped Carbon Quantum Dots: Turn-Off Fluorescent Probe for Dopamine Detection.
In this report, Boron-doped carbon quantum dots (BCQD, size = 2.3 nm) were fabricated by modified hydrothermal carbonization method by one-pot synthesis using phenyl boronic acid as the common precursor that provided seed for the formation of carbon quantum dots as well as the dopant. These quantum dots exhibited excellent properties including aqueous dispersibility, strong fluorescence emission, good environmental stability, highselectivity and sensitivity towards the neurochemical, dopamine even in the absence of any linker or functionalizing agents. It is shown that this material can be used as a "turn off" fluorescent probe for the detection of even low concentration of dopamine with a minimum detection limit of ~6 μM. The simplicity of synthesis protocol and the easiness of dopamine detection define the novelty of this approach.


Effects of increased cerebrospinal fluid pressure on cochlear and cerebral blood flow.
We investigated the effects of increased cerebrospinal fluid (CSF) pressure on cochlear blood flow (CoBF) and cerebral blood flow (CBF) in guinea pigs. CoBF and CBF were recorded simultaneously using two laser-Doppler flowmeters, and blood flow volume in each part of the cochlea and the brain was measured by the non-radioactive microsphere method. CoBF was reduced by increased CSF pressure but the reduction was not persistent. Although inner ear pressure was elevated to the same level as CSF pressure, CoBF was not decreased by the pressure elevation as much as was CBF. Our results suggest that CoBF is relatively resistant to increases in CSF pressure.


Fast two-dimensional MR imaging by multiple acquisition with micro B(0) array (MAMBA).
A new method for acquiring MR data in two dimensions is described. This is achieved by combining coils into an array so as to produce a unique local magnetic field within each coil when placed within the B(0) field of a standard MRI scanner. In this way each known location of a coil is associated with a unique resonant frequency. Each coil now represents a location of a pixel in the plane, and after Fourier transformation of the signal the resulting frequency spectrum gives immediately the spin distribution in the plane of the array. In effect, the two-dimensional spatial distribution is frequency encoded without the use of switched gradients or phase encoding. As only static fields are used, this technique offers the potential of fast imaging. Furthermore, signals from different locations would also be inherently time-registered. Initial experiments to demonstrate the principle are described, using a square array of 5 by 5 coils. The currents in the coils were determined by using a genetic algorithm. Echoes from pellet phantoms placed in the array were acquired using standard spin-echo sequences with gradients switched off. The results are promising, with the spectra showing generally good resolution between peaks, enabling localisation in up to half the pixels. Technical difficulties are discussed and possible applications are outlined.


Duration and onset of action of high dose U-500 regular insulin in severely insulin resistant subjects with type 2 diabetes.
Although regular human U-500 insulin (U-500) is frequently used for insulin resistant type 2 diabetics, pharmacokinetic and pharmacodynamic studies in these individuals are lacking. We set out to determine the rate of onset, duration of action and total glucose lowering effect of two doses of U-500 insulin in obese insulin resistant subjects with type 2 diabetes. Randomized double-blind crossover study was designed to study subjects who were administered either 100 or 200 units SQ of U-500 insulin once and then were provided intravenous glucose as necessary to maintain euglycaemia. A total of 12 subjects were studied. The time during which intravenous glucose was required to maintain euglycaemia following a 200-unit dose of U-500 insulin was significantly greater than the time following a 100-unit dose. No differences were found between doses in measures related to the rate of onset or in the total amount of intravenous glucose required to maintain euglycaemia for the duration of the study. The duration of action of U-500 increases when dose is increased from 100 to 200 units. Neither dose of U-500 insulin has an onset of action before 2.5 hours after administration. This suggests that U-500 should not be used as a premeal bolus insulin to lower glucose two hours after a meal and that dosing intervals might need to be extended as dose is increased to avoid hypoglycaemia.


Abnormal technetium-99m pyrophosphate images in unstable angina: ischemia versus infarction?
There is controversy concerning the specificity of myocardial infarct imaging with technetium-99m pyrophosphate due to the high frequency of false positive images, especially in patients with unstable angina. In this study technetium-99m pyrophosphate images were compared with frequent determinations of plasma creatine kinase, MB isoenzyme (MB CK) activity in 116 patients admitted with the diagnosis of unstable angina. It was hypothesized that frequent measurement of MB CK activity, a sensitive and specific marker for myocardial necrosis, using sensitive assay techniques would detect small amounts of myocardial necrosis which might have been unrecognized by conventional clinical methods. The scintigraphic results and isoenzyme determinations agreed in 88 percent of patients; both tests were normal in 69 percent and both were abnormal, indicating acute myocardial infarcation, in 19 percent of patients. In the remaining 14 patients (12 percent), the scans were abnormal, but MB CK activity was normal. In five of these patients (4 percent), abnormal scintigrams presumably reflected persistent scan positivity after previous myocardial infarction. Only the remaining nine patients (8 percent) could be classified as having unexplained false positive scans, a frequency substantially less than that reported by other investigators who based the diagnosis of myocardial infarction on conventional clinical criteria. These results suggest that abnormal technetium-99m pyrophosphate images in patients with unstable angina generally indicate myocardial necrosis.


Tracing Mississippi River influences in estuarine food webs of coastal Louisiana.
The Breton Sound estuary in southern Louisiana receives large amounts of Mississippi River water via a controlled diversion structure at the upstream end of the estuary. We used stable isotopes to trace spatial and seasonal responses of the downstream food web to winter and spring introductions of river water. Analysis of delta13C, delta15N, and delta34S in the common local consumers such as grass shrimp (Palaemonetes sp.), barnacles (Balanus sp.), and small plankton-feeding fish (bay anchovies, Anchoa mitchilli) showed that the diversion was associated with two of the five major source regimes that were supporting food webs: a river regime near the diversion and a river-influenced productive marsh regime farther away from the diversion. Mixing models identified a third river-influenced source regime at the marine end of the estuary where major natural discharge from the Bird's Foot Delta wraps around into estuarine waters. The remaining two source regimes represented typical estuarine conditions: local freshwater sources especially from precipitation and a brackish source regime representing higher salinity marine influences. Overall, the Mississippi River diversion accounted for 75% of food web support in the upper estuary and 25% in the middle estuary, with influence strongest along known flow pathways and closest to the diversion. Isotopes also traced seasonal changes in river contributions, and indicated increased plant community productivity along the major flow path of diversion water. In the Breton Sound estuary, bottom-up forcing of food webs is strongly linked to river introductions and discharge, occurring in spatial and temporal patterns predictable from known river input regimes and known hydrologic circulation patterns.


Expansion of protein interaction maps by phage peptide display using MDM2 as a prototypical conformationally flexible target protein.
Expanding on the possible protein interaction partners in a biochemical pathway is one key molecular goal in the post-genomic era. Phage peptide display is a versatile in vitro tool for mapping novel protein-protein interfaces and the advantage of this technique in expanding protein interaction maps is that in vitro manipulation of the bait protein conformational integrity can be controlled carefully. Phage peptide display was used to expand on the possible types of binding proteins for the conformationally responsive protein MDM2. Peptides enriched differ depending upon whether MDM2 is ligand-free, zinc-bound, or RNA-bound, suggesting that MDM2 conformational changes alter the type of peptide ligands enriched. Classes of putative/established MDM2-binding proteins identified by this technique included ubiquitin-modifying enzymes (F-box proteins, UB-ligases, UBC-E1) and apoptotic modifiers (HSP90, GAS1, APAF1, p53). Of the many putative MDM2 proteins that could be examined, the impact of HSP90 on MDM2 activity was studied, since HSP90 has been linked with p53 protein unfolding in human cancers. Zinc ions were required to reconstitute a stable MDM2-HSP90 protein complex. Zinc binding converted MDM2 from a monomer to an oligomer, and activated MDM2 binding to its internal RING finger domain, providing evidence for a conformational change in MDM2 protein when it binds zinc. Reconstitution of an HSP90-MDM2 protein complex in vitro stimulated the unfolding of the p53 tetramer. A p53 DNA-binding inhibitor purified from human cells that is capable of unfolding p53 at ambient temperature in vitro contains co-purifying pools of HSP90 and MDM2. These data highlight the utility of phage peptide display as a powerful in vitro method to identify regulatory proteins that bind to a conformationally flexible protein like MDM2.


The Association Between Serum Leptin Levels and Post-Stroke Depression: A Retrospective Clinical Study.
To investigate the question of whether serum leptin levels might be associated with post-stroke depression. We studied 130 patients who experienced a first episode of stroke of more than three months' duration, without any previous history of depression or speech disorders. Data were collected regarding the patient demographics, depressive mood (Diagnostic and Statistical Manual of Mental Disorders 4th edition [DSM-IV] criteria and Beck Depression Inventory) and serum leptin levels measured by an enzyme-linked immunosorbent assay (ELISA). In addition, the Korean version of Modified Barthel Index (K-MBI) and Korean version of Mini-Mental State Examination (K-MMSE) were used to assess the subjects' independence, in regard to the activities of daily living and cognition. A statistical analysis was performed to determine differences the serum leptin levels between patients with depression and those without depression, and to determine the difference in the MBI and K-MMSE scores between the groups separated according to the serum leptin levels. Higher serum leptin levels were observed in patients with depression, compared with those without depression (38.5 ng/mL [range, 25.1-59.2 ng/mL] vs. 8.2 ng/mL [range, 4.9-17.8 ng/mL]; p<0.01. The serum leptin level showed an association with depression (odds ratio, 1.21; 95% confidence interval, 1.01-1.45; p=0.021). The K-MMSE and K-MBI improvement scores were lower, with statistical significance, in the group with the highest leptin level (>30 mg/dL), compared to the other two groups. High serum leptin levels are associated with depression after stroke, and patients with elevated serum leptin levels were disadvantaged in regard to functional and cognitive outcomes.


Donor conceived offspring conceive of the donor: the relevance of age, awareness, and family form.
Rarely have donor conceived offspring been studied. Recently, it has become more common for parents to disclose the nature of conception to their offspring. This new development raises questions about the donor's place in the offspring's life and identity. Using surveys collected by the Donor Sibling Registry, the largest U.S. web-based registry, during a 15 week period from October 2009 to January 2010, we found that donor offspring view the donor as a whole person, rather than as simple genetic material (he can know you; he has looks; he can teach you about yourself); they also believe that the donor should act on his humanity (he should know about you and not remain an anonymous genetic contributor). Other new issues that emerge from this research include the findings that offspring may want to control the decision about contacting their sperm donor in order to facilitate a bond between themselves and the donor that is separate from their relationship with their parents. They also wish to assure their parents that their natal families are primary and will not be disrupted. We discuss how the age at which offspring learned about their donor conception and their current age each make a difference in their responses to what they want from contact with their donor. Family form (heterosexual two-parent families and lesbian two-parent families) also affects donor terminology. The role of the genetic father is reconsidered in both types of families. Donor conceived offspring raised in heterosexual families discover that their natal father no longer carries biological information and he is relegated to being "only" a social father. Offspring raised by lesbian couples experience a dissipation of the family narrative that they have no father. The donor, an imagined father, offers clues to the offspring's personal identity. The natal family is no longer the sole keeper of identity or ancestry.


Agitation and aeration effects in suspension mammalian cell cultures.
Three different hybridoma cell lines, grown in serum-free media with different levels of Pluronic F-68, were subjected to a shear force of 0.6 N m(-2). Some protective effect due to the polymer was found, indicating it to be a potentially useful adjuvant in serum-free media. Other observations of liquid and gas effects at the reactor level have been included here. A discussion of the difference between suspension and microcarrier cultures, in relation to hydrodynamic effects, is included.


Glutathione activation of an organometallic half-sandwich anticancer drug candidate by ligand attack.
In contrast to the clinical drug cisplatin, the anticancer complex [Os(η6-p-cymene)(4-(2-pyridylazo)-N,N-dimethylaniline)I]+ [1-I] is inert towards hydrolysis and targets cancer cell metabolism rather than DNA. A combination of DFT calculations and X-ray absorption spectroscopy (XAS) suggests that hydrolytic activation of 1-I involves catalytic attack by the intracellular tripeptide glutathione (GSH) on the azo bond of the chelating ligand in the complex.


SAS Care 1: sleep-disordered breathing in acute stroke an transient ischaemic attack - prevalence, evolution and association with functional outcome at 3 months, a prospective observational polysomnography study.
Sleep-disordered breathing (SDB) is frequent in patients with acute stroke. Little is known, however about the evolution of SDB after stroke. Most of our knowledge stems from smaller cohort studies applying limited cardiopulmonary sleep recordings or from cross-sectional data collected in different populations. This study aims to determine prevalence, type and intra-individual evolution of SDB based on full-night polysomnography (PSG) in acute stroke and 3 months thereafter. Furthermore, we aimed to identify predictors of SDB in the acute and chronic phase and to evaluate associations between SDB and functional outcome at 3 months (M3). A total of 166 patients with acute cerebrovascular events were evaluated by full PSG at baseline and 105 again at M3. The baseline prevalence of SDB (apnoea-hypopnoea index (AHI)>5·h-1) was 80.5% and 25.4% of the patients had severe SDB (AHI>30·h-1). Obstructive sleep apnoea was more prevalent than central sleep apnoea (83.8% versus 13%). Mean±SD AHI was 21.4±17.6·h-1and decreased significantly at M3 (18±16.4·h-1; p=0.018). At M3, 91% of all patients with baseline SDB still had an AHI>5·h-1 and in 68.1% the predominant type of SDB remained unchanged (78.9% in obstructive sleep apnoea and 44.4% in central sleep apnoea). The only predictors of SDB at baseline were higher age and body mass index and in the chronic phase additionally baseline AHI. Baseline AHI was associated with functional outcome (modified Rankin score >3) at M3. The high prevalence of SDB in acute stroke, its persistence after 3 months, and the association with functional outcome supports the recommendation for a rapid SDB screening in stroke patients.


Natural variation at FLM splicing has pleiotropic effects modulating ecological strategies in Arabidopsis thaliana.
Investigating the evolution of complex phenotypes and the underlying molecular bases of their variation is critical to understand how organisms adapt to their environment. Applying classical quantitative genetics on a segregating population derived from a Can-0xCol-0 cross, we identify the MADS-box transcription factor FLOWERING LOCUS M (FLM) as a player of the phenotypic variation in plant growth and color. We show that allelic variation at FLM modulates plant growth strategy along the leaf economics spectrum, a trade-off between resource acquisition and resource conservation, observable across thousands of plant species. Functional differences at FLM rely on a single intronic substitution, disturbing transcript splicing and leading to the accumulation of non-functional FLM transcripts. Associations between this substitution and phenotypic and climatic data across Arabidopsis natural populations, show how noncoding genetic variation at a single gene might be adaptive through pleiotropic effects.


Herpes virus infection as a cofactor in carcinogenesis: supernatants of herpes virus type 1- and type 2-infected cell cultures contain a cell growth-stimulating factor.
Some cell cultures synthesize a mitogenic factor (DNASF) following their lytic infection with either HSV-1 or HSV-2 which is shed into the medium. Of six cell lines permissive to HSV infection tested, three produce DNASF (CV1, HF, MCA) and a significantly higher (3H)-TdR incorporation was obtained with indicator cells growing in supernatants of virus-infected cells (SupV+) than in the corresponding supernatants of sham-treated cells (SupV-). Sometimes the values obtained with SupV+ exceed those obtained with cell controls, which demonstrates that DNASF is not simply a nutritional factor. Other cell lines do not produce DNASF (HeLa, Wistar and probably REF) and SupV+ frequently inhibit cell growth. DNASF is genetically nonspecific and all indicator cells tested were stimulated by supernatants which contain the mitogen, including the nonpermissive DC-3F cells. The quantity of DNASF induced is directly proportional to the number of cells in the culture and its production peaks when the lysis of the cells is complete. It is not accumulated inside the cells.


Efficient plant regeneration from leaves of rapeseed (Brassica napus L.): the influence of AgNO3 and genotype.
Factors influencing reliable shoot regeneration from leaf explants of rapeseed (Brassica napus L.) were examined. Addition of AgNO(3) to callus induction medium was significantly effective for shoot regeneration in all three genotypes initially tested. When 48 genotypes subsequently were surveyed, a large variation of shoot regenerability was observed, ranging from 100 to 0% in frequency of bud formation and from 7.5 to 0 in the number of buds per explant. A significant correlation (r=0.84) was observed between the frequency of bud formation and the number of buds per explant. The shoot regenerability from leaf explants was not related to that from cotyledonary explants (r=0.28). Histological observations showed that an organized structure developed from calluses produced at vascular bundle tissues after 7 days of culture on callus induction medium, and they developed shoot apical meristems one week after transfer onto shoot induction medium. Regenerated plantlets were obtained 2 months after the initiation of culture and they normally flowered and set seeds. No alterations of morphology or DNA contents were observed in regenerated plants and their S1 progenies.


Safety of ixekizumab in patients with psoriatic arthritis: data from four clinical trials with over 2000 patient-years of exposure.
Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin 17A (IL-17A), has shown significant efficacy in the treatment of psoriatic arthritis (PsA) and sustained long-term clinical response without unexpected new safety outcome for an IL-17A inhibitor. Here, we report the updated safety profile of ixekizumab up to 3 years in patients with PsA. This is an integrated safety analysis from four clinical trials in patients with PsA who received at least one dose of ixekizumab. Treatment-emergent adverse events (TEAEs) and selected adverse events (AEs) exposure-adjusted incidence rates (EAIRs) per 100 patient-years up to 3 years of exposure are reported. A total of 1401 patients with a cumulative ixekizumab exposure of 2247.7 patient-years were included in this analysis. The EAIR of patients with ≥1 TEAE was 50.3 per 100 patient-years and most TEAEs were mild to moderate in severity. Serious AEs were reported by 134 patients (EAIR=6.0). The most reported TEAEs were nasopharyngitis (EAIR=9.0) and upper respiratory tract infection (EAIR=8.3). Infections in general and injection site reactions were the most common TEAEs; the incidence rates of serious cases were low (EAIR ≤1.2). The EAIRs of malignancies (EAIR=0.7), inflammatory bowel disease (EAIR=0.1) including ulcerative colitis and Crohn's disease, depression (EAIR=1.6), and major adverse cerebro-cardiovascular events (EAIR=0.5) were low. As assessed, based on year of exposure, incidence rates were decreasing or constant over time. In this analysis, the overall safety profile and tolerability of ixekizumab are consistent with the known safety profile in patients with PsA. No new or unexpected safety events were detected. NCT01695239, NCT02349295, NCT02584855, NCT03151551.


Whole-body and Whole-Organ Clearing and Imaging Techniques with Single-Cell Resolution: Toward Organism-Level Systems Biology in Mammals.
Organism-level systems biology aims to identify, analyze, control and design cellular circuits in organisms. Many experimental and computational approaches have been developed over the years to allow us to conduct these studies. Some of the most powerful methods are based on using optical imaging in combination with fluorescent labeling, and for those one of the long-standing stumbling blocks has been tissue opacity. Recently, the solutions to this problem have started to emerge based on whole-body and whole-organ clearing techniques that employ innovative tissue-clearing chemistry. Here, we review these advancements and discuss how combining new clearing techniques with high-performing fluorescent proteins or small molecule tags, rapid volume imaging and efficient image informatics is resulting in comprehensive and quantitative organ-wide, single-cell resolution experimental data. These technologies are starting to yield information on connectivity and dynamics in cellular circuits at unprecedented resolution, and bring us closer to system-level understanding of physiology and diseases of complex mammalian systems.


HlyF, an underestimated virulence factor of uropathogenic Escherichia coli.
Urinary tract infections (UTIs) are primarily caused by uropathogenic Escherichia coli (UPEC). This study aims to elucidate the role of the virulence factor HlyF in the epidemiology and pathophysiology of UTIs and investigate the dissemination of plasmids carrying the hlyF gene. An epidemiological analysis was conducted on a representative collection of 225 UPEC strains isolated from community-acquired infections. Selected hlyF+ strains were fully sequenced using a combination of Illumina and Nanopore technologies. To investigate the impact of HlyF, a murine model of UTI was utilized to compare clinical signs, bacterial loads in the bladder, kidney, and spleen, onset of bacteraemia, and inflammation through cytokine quantification among wild-type hlyF+ strains, isogenic mutants, and complemented mutants. Our findings demonstrate that 20% of UPEC encode the HlyF protein. These hlyF+ UPEC strains exhibited enhanced virulence, frequently leading to pyelonephritis accompanied by bloodstream infections. Unlike typical UPEC strains, hlyF+ UPEC strains demonstrate a broader phylogroup distribution and possess a unique array of virulence factors and antimicrobial resistance genes, primarily carried by ColV-like plasmids. In the murine UTI model, expression of HlyF was linked to the UPECs' capacity to induce urosepsis and elicit an exacerbated inflammatory response, setting them apart from typical UPEC strains. Overall, our results strongly support the notion that HlyF serves as a significant virulence factor for UPECs, and the dissemination of ColV-like plasmids encoding HlyF warrants further investigation.


Engineering bunched Pt-Ni alloy nanocages for efficient oxygen reduction in practical fuel cells.
Development of efficient and robust electrocatalysts is critical for practical fuel cells. We report one-dimensional bunched platinum-nickel (Pt-Ni) alloy nanocages with a Pt-skin structure for the oxygen reduction reaction that display high mass activity (3.52 amperes per milligram platinum) and specific activity (5.16 milliamperes per square centimeter platinum), or nearly 17 and 14 times higher as compared with a commercial platinum on carbon (Pt/C) catalyst. The catalyst exhibits high stability with negligible activity decay after 50,000 cycles. Both the experimental results and theoretical calculations reveal the existence of fewer strongly bonded platinum-oxygen (Pt-O) sites induced by the strain and ligand effects. Moreover, the fuel cell assembled by this catalyst delivers a current density of 1.5 amperes per square centimeter at 0.6 volts and can operate steadily for at least 180 hours.


Outcome of childhood ulcerative colitis at 2 years.
Ulcerative Colitis (UC) has an incidence of 1.4 per 100,000 in childhood. There is a paucity of data regarding outcome particularly with the increased use of early immunosuppression. This study reviews outcome at 2 years in a cohort with UC referred to a single centre. Patients were recruited on the basis of a diagnosis made between 2000 and 2003 as a consecutive cohort. All had UC according to standard clinicopathological criteria. Children with indeterminate colitis were excluded. Follow-up data was collected at 2 years by case notes review. Thirty-two children are reported. The median age at diagnosis was 11 years (range 2-16). All were treated with corticosteroids and 5-ASA derivatives at diagnosis. The majority of patients (94%, 30/32) received more than one course of steroids. By 2 years azathioprine use was high with 75% (24/32) of patients on treatment for steroid-dependent disease. There were 6 extra-intestinal manifestations and 8 disease related complications occurring in 12 patients (38%). The colectomy rate was 9% (3/32) for unresponsive disease. There is a high need for Azathioprine in childhood UC. Colectomy rate at 2 years was around 10%. Extra-intestinal manifestations and disease related complications are common.


Physical and chemical properties of Coarse Woody Debris submitted to the natural process of decomposition in a Secondary Atlantic Forest Fragment in Brazil.
Coarse Woody Debris (CWDs) are constantly exposed to the natural decomposition process of wood, which can lead to a change in its physical-chemical properties. However, these changes have not yet been fully elucidated, requiring further studies to help to understand the effect of this process on CWDs degradation. Thus, the objectives of this study were: (i) verify if the decomposition affects the physical-chemical properties of the CWDs; (ii) verify if the structural chemical composition of the CWDs is altered as a function of decomposition, using immediate chemical and thermogravimetric analysis. Wood samples were collected from the CWDs to carry out these analyses, considering pieces with diameters ≥ 5 cm separated into 4 decay classes. The results indicated that the average apparent density decreased as a function of the increase of CWDs decomposition (0.62-0.37 g cm-3). The averages contents of Carbon and Nitrogen suffered less impact with the increase of CWDs decompositions, ranging from 49.66 to 48.80% and 0.52 to 0.58%, respectively. Immediate chemical and thermogravimetric analysis indicated a loss of holocelluloses and extractives and an increase in the concentration of lignin and ash throughout the decomposition process. The weight loss analyzed by thermogravimetric analysis was greater for less decomposed CWDs and with larger diameters. The use of these analyzes removes the subjectivity of CWDs decay classes, reducing the number of tests to determine CWDs physical-chemical properties and increasing the studies accuracy focused on the carbon cycle of these materials.


Synthesis of Pyridoclax Analogues: Insight into Their Druggability by Investigating Their Physicochemical Properties and Interactions with Membranes.
Pyridoclax is considered a promising anticancer drug, acting as a protein-protein interaction disruptor, with potential applications in the treatment of ovarian, lung, and mesothelioma cancers. Eighteen sensibly selected structural analogues of Pyridoclax were synthesized, and their physicochemical properties were systematically assessed and analyzed. Moreover, considering that drug-membrane interactions play an essential role in understanding the mode of action of a given drug and its eventual toxic effects, membrane models were used to investigate such interactions in bulk (liposomes) and at the air-water interface. The measured experimental data on all original oligopyridines allowed the assessment of relative differences in terms of physicochemical properties, which could be determinant for their druggability, and hence for drug development.


Modification of HLA expression on peripheral lymphocytes and monocytes during aging.
Immunosenescence involves modifications of humoral and cellular immunity. Here we report the analysis of human leukocyte antigen (HLA) expression on T lymphocytes, B lymphocytes and monocytes of 58 healthy subjects aged 23-95 years old. Using a double staining immunofluorescence and flow cytometry analysis, we have determined the percentages of cells expressing HLA class-I and HLA-DR antigens. The number of antigenic sites expressed per cell were evaluated for HLA-ABCw, HLA-A, HLA-B, HLA-DR locus with a flow cytometry quantification technique. With advancing age, we observed: (i) a significant decrease of the percentage of T cells and B cells expressing HLA-A products; (ii) a decrease of the number of HLA class-I antigenic sites expressed per cell on the three populations tested, predominantly on B cells and in a locus-dependent fashion; (iii) a decrease of the number of HLA-DR molecules expressed per T cell, although the percentage of T cells expressing DR products was increased; (iv) a significant diminution of the percentage of B cells expressing HLA-DR molecules, without changes of the number of HLA-DR antigenic sites per cells. These changes in HLA expression with increasing age could contribute to the decreased level of immunologic responsiveness observed with ageing and contribute to the modification of antigen recognition.


[Undifferentiated sarcoma of the liver: a rare tumor of childhood].
Undifferentiated sarcoma of the liver is a rare primary tumor of childhood: only about 150 cases have been reported in the literature. A 10 year-old girl was admitted because of diarrhea and weight loss. Sonography, then CT-scan and MRI showed a large tumor of the liver. In the differential diagnosis of primary liver tumors in children, one should think about undifferentiated sarcoma of the liver, especially if imaging shows haemorrhagic foci and if sonography and CT/MRI display a discordant appearance. Survival has improved in the last decade due to agressive surgery and intensive chemotherapy.


On kth-order slant weighted Toeplitz operator.
Let β = [formula: see text] be a sequence of positive numbers with β0 = 1, 0 < β(n)/β(n+1) ≤ 1 when n ≥ 0 and 0 < β(n)/β(n-1) ≤ 1 when n ≤ 0. A kth-order slant weighted Toeplitz operator on L(2)(β) is given by U(φ) = W(k)M(φ), where M(φ) is the multiplication on L(2)(β) and W(k) is an operator on L(2)(β) given by W(k)e(nk)(z) = (β(n)/β(nk))e(n)(z), [formula: see text] being the orthonormal basis for L(2)(β). In this paper, we define a kth-order slant weighted Toeplitz matrix and characterise U(φ) in terms of this matrix. We further prove some properties of U(φ) using this characterisation.


Genital herpes. Type-specific antibodies for diagnosis and management.
The high incidence of unrecognized genital herpes infections and the role of such undiagnosed infections in continuing the spread of genital herpes has been due, in part, to the limited availability of accurate serologic assays for herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Type-specific serology test kits for HSV diagnosis have been developed and are expected to be widely available in 1998. Clinicians should understand the proper application of these new test and in addition, should be aware that older, inaccurate test will remain on the market for the foreseeable future.


Non-classical effects of estradiol on cAMP responsive element binding protein phosphorylation in gonadotropin-releasing hormone neurons: mechanisms and role.
Gonadotropin-releasing hormone (GnRH) is produced by a heterogenous neuronal population in the hypothalamus to control pituitary gonadotropin production and reproductive function in all mammalian species. Estradiol is a critical component for the communication between the gonads and the central nervous system. Resolving the mechanisms by which estradiol modulates GnRH neurons is critical for the understanding of how fertility is regulated. Extensive studies during the past decades have provided compelling evidence that estradiol has the potential to alter the intracellular signal transduction mechanisms. The common target of many signaling pathways is the phosphorylation of a key transcription factor, the cAMP response element binding protein (CREB). This review first addresses the aspects of estradiol action on CREB phosphorylation (pCREB) in GnRH neurons. Secondly, this review considers the receptors and signaling network that regulates estradiol's action on pCREB within GnRH neurons and finally it summarizes the physiological significance of CREB to estrogen feedback.


A novel metabolic network leads to enhanced citrate biogenesis in Pseudomonas fluorescens exposed to aluminum toxicity.
Aluminum (Al), an environmental toxin, is known to have a negative impact on various biological systems. However, some microbes have devised intricate mechanisms to combat the toxic influence of this trivalent metal. In this study, Pseudomonas fluorescens grown in malate invoked a unique metabolic shift to promote the synthesis of citrate, a metabolite involved in the sequestration of Al. Electrophoretic and spectrophotometric assays revealed several malate-metabolizing enzymes including malate dehydrogenase (MDH) and malic enzyme (ME) displayed increases in activity and expression in the Al-treated cells. Whereas pyruvate dehydrogenase (PDH) also showed increased activity and expression in the Al-stressed cultures, phosphoenolpyruvate carboxykinase (PEPCK) displayed a marked diminution in the Al-treated cells. The upregulation of citrate synthase (CS) coupled with the diminished activities of aconitase (ACN) and NAD-isocitrate dehydrogenase (NAD-ICDH) appeared to be instrumental in the accumulation of citrate. HPLC experiments revealed high levels of citrate in the Al-stressed cultures. Thus, an Al-enriched environment provoked a metabolic shift in P. fluorescens dedicated to the conversion of malate to citrate.


Astragaloside IV attenuates lead acetate-induced inhibition of neurite outgrowth through activation of Akt-dependent Nrf2 pathway in vitro.
Recently, oxidative stress is strongly associated with lead (Pb)-induced neurotoxicity. We reported previously that Astragaloside IV (AS-IV) possesses potent antioxidant properties. Here, we evaluate the hypothesis that AS-IV attenuates lead acetate (PbAc)-mediated inhibition of neurite outgrowth might mainly result from its antioxidant property via serine/threonine protein kinase (Akt)-dependent activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Interestingly, AS-IV attenuates PbAc-induced inhibition of neurite outgrowth and displayed potential antioxidant properties by inhibiting reactive oxygen species (ROS). Concomitantly, AS-IV enhanced phase II detoxifying enzymes such as heme oxygenase 1 (HO-1), thioredoxin reductase (TrxR), and glutamate cysteine ligase catalytic subunit (GCLc). Conversely, AS-IV had no effect on GCL modulatory subunit (GCLm) and superoxide dismutase (SOD) activity/expression. Furthermore, AS-IV evoked Akt phosphorylation, and subsequent induced phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9 (that is, inactivation), which stimulated Nrf2-mediated antioxidant response element (ARE)-containing activation. Importantly, Akt locates upstream of GSK-3β and regulates phase II detoxifying enzymes gene expression through Nrf2 nuclear accumulation in PC12 cells exposed to PbAc. Noteworthy, these results were further confirmed through signalling pathway inhibitors, dominant negative mutant and short hairpin RNA technology. Collectively, these in vitro findings suggest that AS-IV attenuates PbAc-induced inhibition of neurite outgrowth attributed to its antioxidant properties and may be a promising candidate for the treatment of lead developmental neurotoxicity.


Blood glucose and lipid concentrations after overload are not associated with the risk of alcohol relapse.
There is evidence for the functioning of feedback between alcohol consumption and fat (positive) and carbohydrate (negative) intake. We tried to verify the hypothesis that blood glucose and lipid concentration in a fasting state and after loading may affect the risk of relapse in alcohol-dependent male patients during withdrawal therapy. Blood glucose, total cholesterol (TC) and triglycerides (TG) were determined at the beginning of the study, and again after 4 weeks and 6 months of observation in 54 alcohol-dependent male patients treated against drinking relapse. Glucose concentration was checked after fasting and 2h after loading with a 75 g water solution of glucose, and blood lipids were determined on an empty stomach and 5h after butter loading (0.5 g of butter per kilogram of body mass). Patients who relapsed compared to subjects who remained abstinent during the 6-month observation did not differ significantly in relation to blood glucose, TC or TG blood concentrations, either in a fasting state or after loading. Patients with an initial above-median increase in TG blood concentration after butter loading (>38%) before the beginning of the study, and who smoked cigarettes with a greater content of nicotine and tar, preferred vodka and had lower values of aminotransferases. Fasting and postprandial blood glucose, TC and TG concentrations had no relationship with the outcome of anti-relapse treatment. However, they presented some associations with the pathomechanism of addiction to nicotine.


Comparison of corneal pachymetry using ultrasound and Orbscan II.
To compare Orbscan II pachymetry with ultrasonic pachymetry in eyes having corneal refractive surgery. Instituto Oftalmológico de Alicante, Alicante, Spain. In this comparative prospective study, 72 eyes (36 patients) were divided into 4 groups: Group 1, 16 eyes with haze after photorefractive keratectomy (PRK); Group 2, 12 eyes with no haze after PRK; Group 3, 24 eyes that had uneventful laser in situ keratomileusis; Group 4, 20 normal eyes. The corneal thickness was measured in all eyes by the Orbscan II (version 3.27.10, Orbtek Inc.) and then by ultrasonic pachymetry (DHC 500, Technology Inc.). The results between the 2 systems of pachymetry were significant in Group 1 (P < .0001) and not significant in Groups 2, 3, and 4 (P = .056, P = .051, and P = .68, respectively). A statistically significant correlation existed between the grade of haze and the decrease in Orbscan readings (C = -0.821, P < .0001). The Orbscan II pachymetry measurements correlated with the ultrasound measurements in eyes with clear corneas. Haze after PRK decreased the Orbscan pachymetry.


The action of human high density lipoprotein on cholesterol crystals. Part 2. Biochemical observations.
Electron microscopy of the reaction product between human pooled high density lipoprotein (HDL) and cholesterol shows that characteristic liposome macromicellar bodies are formed. These bodies vary in size between 30 and 1200 nm. In comparison with HDL, they contain markedly more cholesterol, but less protein and phospholipid. Their phospholipid pattern shows enrichment with sphingomyelin and phosphatidyl serine in comparison with HDL.


Uncovering the key pharmacodynamic material basis and possible molecular mechanism of extract of Epimedium against liver cancer through a comprehensive investigation.
Liver cancer is a worldwide malignant tumor, and currently lacks effective treatments. Clinical studies have shown that epimedium (YYH) has therapeutic effects on liver cancer, and some of its prenylflavonoids have demonstrated anti-liver cancer activity through multiple mechanisms. However, there is still a need for systematic research to uncover the key pharmacodynamic material basis and mechanism of YYH. This study aimed to screen the anti-cancer material basis of YYH via integrating spectrum-effect analysis with serum pharmacochemistry, and explore the multi-target mechanisms of YYH against liver cancer by combining network pharmacology with metabolomics. The anti-cancer effect of the extract of YYH (E-YYH) was first evaluated in mice with xenotransplantation H22 tumor cells burden and cultured hepatic cells. Then, the interaction between E-YYH compounds and the cytotoxic effects was revealed through spectrum-effect relationship analysis. And the cytotoxic effects of screened compounds were verified in hepatic cells. Next, UHPLC-Q-TOF-MS/MS was employed to identify the absorbed components of E-YYH in rat plasma to distinguish anti-cancer components. Subsequently, network pharmacology based on anti-cancer materials and metabolomics were used to discover the potential anti-tumor mechanisms of YYH. Key targets and biomarkers were identified and pathway enrichment analysis was performed. The anti-cancer effect of E-YYH was verified through in vitro and in vivo experiments. Six anti-cancer compounds in plasma (icariin, baohuoside Ⅰ, epimedin C, 2″-O-rhamnosyl icariside Ⅱ, epimedin B and sagittatoside B) were screened out by spectrum-effect analysis. Forty-five liver-cancer-related targets were connected with these compounds. Among these targets, PTGS2, TNF, NOS3 and PPARG were considered to be the potential key targets preliminarily verified by molecular docking. Meanwhile, PI3K/AKT signaling pathway and arachidonic acid metabolism were found to be associated with E-YYH's efficacy in network pharmacology and metabolomics analysis. Our research revealed the characteristics of multi-component, multi-target and multi-pathway mechanism of E-YYH. This study also provided an experimental basis and scientific evidence for the clinical application and rational development of YYH.


Late effects on human bone marrow after extended field radiotherapy.
Thirty-two patients with lymphoma were treated with extended radiotherapy (RT) at a dose of Gy and were studied by ferrokinetic studies and surface counting at various times following irradiation. Loss of hematopoietic activity in the irradiated areas is compensated by increased activity in the non-irradiated areas. Despite the return of peripheral blood counts to normal, the hyperactivity of the non-irradiated bone marrow persists over up to 13 years after RT, while the hematopoietic activity of the irradiated areas remains depressed and is only slightly higher than immediately after RT. The hypoactivity persisted even when the hemopoietic tissues had been subjected to the intense stimulation provoked by an aplasia caused by chemotherapy. However, a recovery was observed for dose of 20 Gy or lower. The hemopoietic activity of the irradiated bone marrow appears to be related to the volume of the marrow irradiated and is higher after a mantle + inverted Y field than after a mantle field. Both marrow scintigraphies with 59Fe in 7 out of 9 patients studied revealed an extension of hematopoiesis into a normally dormant area of the marrow, such as the femora. In 2 patients an erythropoietic activity was observed in spleens which had received a dose of 40 Gy, and extra medullary erythropoiesis was found in approximately two-thirds of the patients.


Concentration of F-actin in synaptic formations of the hippocampus as visualized by staining with fluorescent phalloidin.
Polymerized actin (F-actin) was localized in the guinea pig hippocampus by fluorescent staining with rhodamine-labeled phalloidin. Phalloidin displayed a preferential affinity for the main synaptic areas where the fluorescence was confined to 0.5-1 micron particles, roughly the size of synaptic structures (dendritic spines and presynaptic terminals). These particles appeared to stud the surface of dendrites. Particularly large and strongly fluorescent particles mainly 1-3 micron in diameter were found in the termination zone of mossy fibres which form the largest synapses of the hippocampus. The apparent high concentration of F-actin in synaptic formations suggests a role for actin in synaptic function.


Adjuvant intravesical chemotherapy of superficial bladder cancer with monthly doxorubicin or intensive mitomycin. A comparison of two consecutive series.
120 patients with the first occurrence of TNM stage Ta or T1 bladder carcinoma were given adjuvant intravesical treatment in 2 consecutive series. The first 60 received doxorubicin monthly for 6 months, then on the 9th and 12th month following surgery. The second series was given mitomycin weekly for 2 months, then monthly to the end of the first year. Median follow-up is 48 months in the first series and 15 in the second. In the doxorubicin group, 28 patients had recurrences. The recurrence rate is 1.86/100 patient-months. Seventeen of these first relapses occurred within the first year. In the 'intensive' mitomycin series, where 36 patients were observed for 12 months or more, 3 relapsed. The recurrence rate to date is 0.35. The relapse-free survival probability at 12 months is 75% in the first series and 93% in the second. Treatment was stopped due to toxicity in 4 patients in the doxorubicin group and in 10 of the mitomycin group.


Cerebral neurovascular alterations in stable chronic obstructive pulmonary disease: a preliminary fMRI study.
Cognitive impairment (CI) is very common in patients with chronic obstructive pulmonary disease (COPD). Cerebral structural and functional abnormalities have been reported in cognitively impaired patients with COPD, and the neurovascular coupling changes are rarely investigated. To address this issue, arterial spin labeling (ASL) and resting-state blood oxygenation level dependent (BOLD) fMRI techniques were used to determine whether any neurovascular changes in COPD patients. Forty-five stable COPD patients and forty gender- and age-matched healthy controls were recruited. Furthermore, resting-state BOLD fMRI and ASL were acquired to calculate degree centrality (DC) and cerebral blood flow (CBF) respectively. The CBF-DC coupling and CBF/DC ratio were compared between the two groups. COPD patients showed abnormal CBF, DC and CBF/DC ratio in several regions. Moreover, lower CBF/DC ratio in the left lingual gyrus negatively correlated with naming scores, lower CBF/DC ratio in medial frontal cortex/temporal gyrus positively correlated with the Montreal Cognitive Assessment (MoCA), visuospatial/executive and delayed recall scores. These findings may provide new potential insights into neuropathogenesis of cognition decline in stable COPD patients.


Rapid development of hepatocellular neoplasms in aging male C3H/HeNCr mice given phenobarbital.
One hundred and nineteen male C3H/HeNCr mice, 12 months of age, with spontaneous preneoplastic and neoplastic hepatocellular lesions were given phenobarbital (PB) at 500 ppm in drinking water. Groups of 9-10 mice were sacrificed after 12, 24 and 36 weeks of PB exposure. Identical numbers of untreated controls were used. A group of 6-week-old C3H/HeNCr mice were also given PB and sacrificed at 12, 24 or 36 weeks. In aging mice, PB exposure significantly increased the number of gross tumors or microscopic foci, adenomas or carcinomas per liver at all time periods, especially unique eosinophilic proliferative lesions, while young mice did not develop any focal proliferative lesions by 36 weeks. These findings suggest that in aging mice a fraction of the hepatocyte population (normal, spontaneously-initiated or preneoplastic) is more highly susceptible to phenobarbital 'carcinogenesis' than are hepatocytes of younger mice.


Introduction of SGRT in clinical practice.
To describe the rationale and process how SGRT was implemented in our department from the original decision to daily clinical practice.


Post-weaning social isolation in male mice leads to abnormal aggression and disrupted network organization in the prefrontal cortex: Contribution of parvalbumin interneurons with or without perineuronal nets.
Adverse social experiences during childhood increase the risk of developing aggression-related psychopathologies. The prefrontal cortex (PFC) is a key regulator of social behavior, where experience-dependent network development is tied to the maturation of parvalbumin-positive (PV+) interneurons. Maltreatment in childhood could impact PFC development and lead to disturbances in social behavior during later life. However, our knowledge regarding the impact of early-life social stress on PFC operation and PV+ cell function is still scarce. Here, we used post-weaning social isolation (PWSI) to model early-life social neglect in mice and to study the associated neuronal changes in the PFC, additionally distinguishing between the two main subpopulations of PV+ interneurons, i.e. those without or those enwrapped by perineuronal nets (PNN). For the first time to such detailed extent in mice, we show that PWSI induced disturbances in social behavior, including abnormal aggression, excessive vigilance and fragmented behavioral organization. PWSI mice showed altered resting-state and fighting-induced co-activation patterns between orbitofrontal and medial PFC (mPFC) subregions, with a particularly highly elevated activity in the mPFC. Surprisingly, aggressive interaction was associated with a higher recruitment of mPFC PV+ neurons that were surrounded by PNN in PWSI mice that seemed to mediate the emergence of social deficits. PWSI did not affect the number of PV+ neurons and PNN density, but enhanced PV and PNN intensity as well as cortical and subcortical glutamatergic drive onto mPFC PV+ neurons. Our results suggest that the increased excitatory input of PV+ cells could emerge as a compensatory mechanism for the PV+ neuron-mediated impaired inhibition of mPFC layer 5 pyramidal neurons, since we found lower numbers of GABAergic PV+ puncta on the perisomatic region of these cells. In conclusion, PWSI leads to altered PV-PNN activity and impaired excitatory/inhibitory balance in the mPFC, which possibly contributes to social behavioral disruptions seen in PWSI mice. Our data advances our understanding on how early-life social stress can impact the maturing PFC and lead to the development of social abnormalities in adulthood.


Biochemical characterization of three stimulatory GTP-binding proteins. The large and small forms of Gs and the olfactory-specific G-protein, Golf.
The biochemical properties of three stimulatory guanine nucleotide-binding protein (G-protein) alpha subunits, the large and small forms of Gs, Gs-l (52 kDa) and Gs-s (45 kDa), and the olfactory specific G-protein, Golf, have been compared. Complementary DNAs (cDNAs) encoding each alpha subunit were independently expressed in a mammalian cell line deficient in endogenous stimulatory G-proteins (S49 cyc-kin-). Gs-l and Gs-s respond similarly to activation by the beta-adrenergic agonist isoproterenol (EC50 = 80 and 60 nM, respectively) and the receptor-independent G-protein activators guanosine 5-O-3-(thio)triphosphate) (GTP gamma S) and AlF-4. The ability of Golf to interact with the beta-adrenergic receptor was also examined. Surprisingly, Golf interacts with beta-adrenergic receptors and is activated by isoproterenol (EC50 = 120 nM). All three G-proteins respond similarly to treatment with different alpha, beta, and gamma thiophosphoryl analogs of GTP. Specifically, (R)-GTP alpha S and GTP gamma S activate each G-protein, whereas (S)-GTP alpha S and (R)- or (S)-GTP beta S are inactive. In addition, similar to Gs alpha, Golf alpha is covalently modified and constitutively activated by cholera toxin. These studies demonstrate that all three stimulatory G-proteins are functionally and structurally similar, however, subtle differences between Golf and the two forms of Gs appear to modulate their interactions with receptors.


Differential effects of sulfonylurea derivatives on vascular ATP-sensitive potassium channels.
Sulfonylurea drugs exert their insulinotropic action by inhibiting ATP-sensitive potassium channels in the pancreas. However, these channels are also expressed in myocardial and vascular smooth muscle, implicating possible detrimental cardiovascular effects. Aim of the present study was to investigate the inhibitory potency of various widely used sulfonylurea drugs in resistance arteries. Isolated mesenteric and renal resistance arteries mounted in a myograph and isolated perfused kidneys were used to measure drug responses. Pinacidil induced a dose-dependent relaxation of phenylephrine preconstricted mesenteric and renal arteries (pEC(50)=6.10 ± 0.01 and 5.66 ± 0.03, respectively). Schild plot analysis of pinacidil relaxation curves in mesenteric arteries in the presence of sulfonylurea antagonists revealed the following order of potency: glimepiride (pA(2)=7.22) ≥ glibenclamide (pA(2)=7.05) > glipizide (pA(2)=5.25) > gliclazide (pA(2)=4.31). The effects of glibenclamide in renal arteries were comparable. Furthermore, glibenclamide produced similar constrictive properties in isolated renal arteries as in isolated perfused whole kidneys. We conclude that sulfonylurea drugs exert differential effects on vascular smooth muscle K(ATP) channels. Our results suggest that glibenclamide and glimepiride will interact with these channels at therapeutic concentrations.


An expedient sequential one-pot four component synthesis of novel steroidal spiro-pyrrolidine heterocycles in ionic liquid.
A facile one-pot synthesis of novel steroidal dispiro-indenoquinoxaline pyrrolidines via multicomponent-[3+2]-cycloaddition of azomethine ylides in ionic liquid is described. The structure of cycloadduct is confirmed by IR, (1)H NMR, (13)C NMR, high resolution mass spectroscopy and elemental analysis.


Surgical and prosthetic treatment of superficial carcinoma of the oral cavity.
A technique has been described for split-thickness skin grafting after resection of superficial carcinoma for both the mandibular and maxillary arch. The technique is a cooperative effort between the surgeon and the prosthodontist.


Association between Toxoplasma gondii exposure and hematological malignancies: A systematic review and meta-analysis.
The possible association between Toxoplasma gondii infection and hematological malignancies has been suggested by several studies. The current systematic review and meta-analysis was directed to further understand this relationship. In the present study, five electronic databases were reviewed for T. gondii infection in patients with blood cancer. The random effects model and 95% confidence intervals (CI) were used to determine the overall odds ratio (OR). Heterogeneity was deliberate with Cochran's Q test and I2 statistic. In total, 13 studies including 1504 patients with hematological neoplasia and 2622 subjects without any malignancies were included in this meta-analysis. Overall, 324 patients with blood cancer and 391 subjects without any malignancies were exposed to Toxoplasma infection. The pooled random effect favored a statistically significant increased risk of T. gondii infection in patients with hematological neoplasia compared with non-cancer individuals [OR = 2.43; 95% CI: 1.49-3.97; χ2 = 49.7, I2 = 75.9%, P = 0.00]. Also, significant pooled ORs of positive association were observed for studies which measured anti- Toxoplasma antibodies (IgG) [OR = 2.66; 95% CI: 1.46-4.83; χ2 = 40.3; I2 = 82.6%, P = 0.00]. T-value and P-value were obtained 0.20 and 0.85 by Harbords modified regression test. This meta-analysis demonstrates that toxoplasmosis may be associated with an elevated risk of hematological malignancies. Also, it has found that immunoglobulin class and types of blood cancer are the specific sources of heterogeneity. Additional studies should be performed to examine the impact of T. gondii infection in the onset or development of hematologic neoplasms in the future.


[Quantum analysis of postsynaptic potentials].
Basic formulations of the quantum theory for synaptic transmission are listed. Methods for determining the mean quantum content, quantum value and binomial parameters describing the amplitude distributions of the unitary and "minimal" postsynaptic potentials are discussed. Literature and author's determinations of the quantum parameters for the synapses of the central nervous system are described. The comparison is made with similar determinations for more studied peripheral junctions. Some difficulties and perspective of the quantum theory are discussed.


[Cardiovascular risk evolution in patients treated for high blood pressure at the Armies Instruction's Hospital of Cotonou].
This study was initiated to determine the progression of the cardiovascular risk (CR) in a 5-years period for those who went through high blood pressure treatment. It is a retrospective and descriptive study over a period of 9 years. Were included in that category, African patients treated in that period of time and who at least benefited from a 5-years medical care period. The total CR was calculated afterwards, for the needs for the study, using the tables of Framingham. All the data were collected after the first evaluation then brought up to date at the terms of 1, 3 and 5 years and with a last consultation for the patients whose medical care follow-up exceeded 5 years. For the 103 patients who had complete data, the average age was of 49.11±8 and the sex ratio of 2. Among them 14 (13.6%) died of cardiovascular complications. Among the 89 remaining patients, the CR at the beginning was very high in a proportion of 10.1%, high in 49.4%, moderated in 22.5% and weak in 18%. The general evolution is characterized by a stability of the proportion of the moderated CR (20 - 23%) and high CR (43 - 50%) but a very important increase in the proportion of the very high CR (10 to 21%) to the detriment of the weak CR (18 to 10%). The analysis of the individual evolution reveals an improvement of the CR among 19 patients (21.3%), its stability among 39 patients (43.8%) and a worsening among 31 patients (34.8%). These data are confirmed in a widened population of 321 patients of which the less complete data allow an estimate of the CR. The cardiovascular risk is difficult to evaluate. It is badly controlled in the long run.


Triatominae (Hemiptera, Reduviidae) in homes: Report of their occurrence in the municipality of Cruzeiro do Sul, Acre, South Western Amazon.
Triatomines are hematophagous insects that are important to public health since they are the vectors of American Trypanosomiasis. The objective of this study was to describe the occurrence of triatomines in homes in Cruzeiro do Sul, Acre, Brazil. The specimens were collected by an active search inside homes and also by a passive search by the residents. A total of 55 triatomines were captured comprising of 5 species each of the genera Rhodnius, Eratyrus, and Panstrongylus. No colonies were detected, ruling out the possibility of domiciliation. Information on regional epidemiological dynamics contributes to the prevention and control of disease.


Solubility and emulsifying properties of perilla protein isolate: Improvement by phosphorylation in the presence of sodium tripolyphosphate and sodium trimetaphosphate.
To investigate the mechanisms of phosphates affecting the solubility and emulsifying properties of perilla protein isolate (PPI), PPI was treated with sodium trimetaphosphate (STMP) and sodium tripolyphosphate (STPP) at different concentrations. FTIR and XPS showed that phosphate groups were bonded to PPI through COP bonds. The introduction of STPP increased the particle size and electronegativity of PPI, resulting in the exposure of hydrophobic groups and free -SH groups, as well as the changes of secondary structure and tertiary conformation. All these variations induced increased oil holding capacity, thermal stability, solubility, emulsifying and foaming properties of PPI, especially at STPP concentration of 8%. Furthermore, o/w emulsions stabilized by STPP-modified PPI exhibited higher stability, which could be attributed to the higher interfacial adsorption protein amount and smaller droplet size. These results indicated that PPI modified by phosphate (especially STPP) can be used in the construction of food-grade emulsion systems.


Effect of varying the gas headspace to meat ratio on the quality and shelf-life of beef steaks packaged in high oxygen modified atmosphere packs.
Beef steaks (M. longissimus dorsi) were stored in modified atmosphere packs (MAP) (80% O₂:20% CO₂) with gas headspace to meat ratios of 2:1, 1:1 and 0.5:1 for 14 days at 4 °C. The pH, surface colour, texture and microbiology of beef steaks were unaffected (P>0.05) by varying the gas headspace to meat ratio. APLSR (ANOVA-partial least squares regression) and jack-knife uncertainty testing indicated that lipid oxidation (TBARS) was significantly positively correlated with days 10 (P<0.05) and 14 (P<0.001) of storage. Chemical and sensory detection of lipid oxidation in beef steaks were in agreement on day 14 of storage. The sensory quality and acceptability of beef steaks were similar in gas headspace to meat ratios of 2:1 or 1:1 and unacceptable in 0.5:1. Results indicate that pack size and gas volume can be reduced without negatively affecting fresh beef quality and shelf-life.


Hodgkin's disease and ataxia telangiectasia with pulmonary cavities.
Ataxia telangiectasia (AT) homozygotes have an increased risk for development of Hodgkin's disease (HD). Parenchymal lung involvement is not uncommon in HD; however, cavitary pulmonary lesions are quite unusual. We report on 3 cases of AT with HD who had mediastinal disease and parenchymal pulmonary involvement with cavitation. Of 6 AT patients in our HD series, 3 developed pulmonary cavities. The patients displayed pulmonary infiltration, cavitation in the lung parenchyma, and mediastinal enlarged lymph nodes on both plain chest X-rays and thoracic computed tomographies. No infectious etiologies were established for the pulmonary findings. Histopathological examination of open lung and mediastinal biopsies revealed HD, and all patients received multiagent chemotherapies. The outcome was fatal in all 3 patients. Respiratory infections are the principle cause for morbidity and mortality in AT patients. Reports on cavitating pulmonary lesions in HD are quite rare. Furthermore, data regarding the patterns of pulmonary involvement in AT patients with or without HD are lacking. The increased incidence of malignancies in AT patients may relate to immunodeficiency and to the chromosomal alterations identified.


Novel phenotype of craniosynostosis and ocular anterior chamber dysgenesis with a fibroblast growth factor receptor 2 mutation.
Fibroblast growth factor receptor 2 (FGFR2) mutations are associated with syndromic and non-syndromic craniosynostoses. More recently it has been recognized that FGFR2 may have a role in the development of the anterior chamber of the eye following the finding of a specific FGFR2 mutation (p.Ser351Cys, c.1231 C --> G) with anterior chamber dysgenesis. Affected patients had a severe craniofacial phenotype and clinical course. A child with a different FGFR2 mutation (p.Ala344Ala, c1032 G --> A heterozygote), premature fusion of the sagittal suture, and an Axenfeld-Rieger anomaly but otherwise normal clinical course is reported. The case provides further evidence that FGFR2 has a role in anterior chamber embryogenesis.


Virtual cardiotomy based on 3-D MRI for preoperative planning in congenital heart disease.
Patient-specific preoperative planning in complex congenital heart disease may be greatly facilitated by virtual cardiotomy. Surgeons can perform an unlimited number of surgical incisions on a virtual 3-D reconstruction to evaluate the feasibility of different surgical strategies. To quantitatively evaluate the quality of the underlying imaging data and the accuracy of the corresponding segmentation, and to qualitatively evaluate the feasibility of virtual cardiotomy. A whole-heart MRI sequence was applied in 42 children with congenital heart disease (age 3 +/- 3 years, weight 13 +/- 9 kg, heart rate 96 +/- 21 bpm). Image quality was graded 1-4 (diagnostic image quality > or =2) by two independent blinded observers. In patients with diagnostic image quality the segmentation quality was also graded 1-4 (4 no discrepancies, 1 misleading error). The average image quality score was 2.7 - sufficient for virtual reconstruction in 35 of 38 patients (92%) older than 1 month. Segmentation time was 59 +/- 10 min (average quality score 3.5). Virtual cardiotomy was performed in 19 patients. Accurate virtual reconstructions of patient-specific cardiac anatomy can be produced in less than 1 h from 3-D MRI. The presented work thus introduces a new, clinically feasible noninvasive technique for improved preoperative planning in complex cases of congenital heart disease.


Stereotactic radiosurgery for essential tremor: Retrospective analysis of a 19-year experience.
Essential Tremor (ET) is a common movement disorder that can be disabling. Initial treatment is in the form of medical therapies. Patients with medically refractory ET seek surgical intervention which include radiofrequency thalamotomy, deep brain stimulation, and radiosurgical thalamotomy. Radiosurgical thalamotomy is a minimally invasive surgical option which is especially valuable for elderly and high surgical risk patients. The purpose of this study was to retrospectively analyze the outcomes of stereotactic radiosurgery for patients suffering from medically refractory essential tremor. During a 19-year period (1996-2015), 73 patients underwent gamma knife thalamotomy for intractable essential tremor. A median central dose of 140 Gy (range, 130-150) was delivered to the nucleus ventralis intermedius through a single 4-mm isocenter. We used the Fahn-Tolosa-Marin clinical tremor rating scale to score tremor, handwriting, drawing, and ability to drink fluids. The median time to last follow-up was 28 months (range, 6-152). After gamma knife thalamotomy, 93.2% improved in tremor. Forty-four patients (60.3%) experienced tremor arrest or barely perceptible tremor. Eighteen patients (24.7%) noted tremor arrest and complete restoration of motor function. Tremor improvement was sustained at last follow-up in 96% of patients who experience tremor relief. Mean tremor score improved from 3.19 before to 1.27 after gamma knife thalamotomy (P < 0.0001). Mean handwriting score improved from 2.97 to 1.25 (P < 0.0001). Mean drawing score improved from 3.16 to 1.26 (P < 0.0001). Mean drinking score improved from 3.14 to 1.56 (P < 0.0001). Imaging follow-up showed three types of lesions: enhancing lesion, streaking along internal capsule on fluid-attenuated inversion recovery, and significant reactive changes. Three patients (4%) experienced temporary adverse radiation effects. Radiosurgery is a safe and valuable treatment option for medically refractory essential tremor, especially for the elderly or those with high surgical risk for DBS or radiofrequency thalamotomy. © 2017 International Parkinson and Movement Disorder Society.


Autosomal recessive microcephaly associated with chorioretinopathy.
Two sisters and their brother affected with microcephaly, microphthalmia, chorioretinal degeneration, and optic atrophy were studied. Besides the clinical features derived from the main abnormalities, nanosomy and cutis marmorata were found in the three patients. Both parents and three other sibs were normal. Possible intrauterine non-genetic etiologic factors (X-rays, toxoplasmosis, cytomegalovirus) which can lead to phenocopies were investigated with negative results. Based on these and previous observations, it seems clear that a distinct form of autosomal recessive microcephaly associated with chorioretinal degeneration can be separated from the heterogenous group of entities which presents microcephaly.


Upregulation of a lymphoid serine protease in kidney allograft recipients.
The presence of a putative, cytotoxicity-linked lymphoid serine esterase (SE) has been studied in 79 kidney graft recipients. Peripheral blood lymphocytes (PBL) bearing an N-alpha-benzyloxy carbonyl-L-lysine thiobenzyl ester (BLT)-specific SE were evaluated by a novel cytochemical staining method. A characteristic of post-allograft patients was an increased presence of SE containing granules in PBL. In 46 patients with stable graft function SE + PBL were 33.41 +/- 10.34% (controls: 26.30 +/- 5.22%, P less than 0.0025), SE + CD4+ 4.32 +/- 3.85% (controls 2.13 +/- 1.52%, P less than 0.0025) and SE + CD8+ T cells 47.68 +/- 18.64% (controls: 28.50 +/- 6.50%, P less than 0.0005). In those graft recipients undergoing a rejection episode a marked upregulation of SE activity could be observed when compared to the stable graft group: SE + PBL were 59.91 +/- 10.89% (P less than 0.0005), SE + CD8+ 74.30 +/- 10.79% (P less than 0.0005) and SE + CD4+ T cells 28.56 +/- 13.50% (P less than 0.0005). In 10 cases this increase of SE activity was observed with a time lag of up to 37 days prior to the onset of clinical or biopsy proven rejections, promptly decreasing in response to methylprednisolone antirejection therapy. In patients with recurrent rejection episodes and subsequent graft loss, a repeating increase of SE activity indicated a failure of therapeutic agents.(ABSTRACT TRUNCATED AT 250 WORDS)


Human responses to high levels of carbon dioxide and air temperature.
In this study, 30 subjects were exposed to different combinations of air temperature (Ta : 24, 27, and 30°C) and CO2 level (8000, 10 000, and 12 000 ppm) in a high-humidity (RH: 85%) underground climate chamber. Subjective assessments, physiological responses, and cognitive performance were investigated. The results showed that as compared with exposure to Ta = 24°C, exposure to 30°C at all CO2 levels caused subjects to feel uncomfortably warm and experience stronger odor intensity, while increased mental effort and greater intensity of acute health symptoms were reported. However, no significant effects of Ta on task performance or physiological responses were found. This indicated that subjects had to exert more effort to maintain their performance in an uncomfortably warm environment. Increasing CO2 from 8000 to 12 000 ppm at all Ta caused subjects to report higher rates of headache, fatigue, agitation, and feeling depressed, although the results were statistically significant only at 24 and 27°C. The text typing performance and systolic blood pressure (SBP) decreased significantly at this exposure, whereas diastolic blood pressure (DBP) and thermal discomfort increased significantly. These effects suggest higher arousal/stress. No significant interaction effect of Ta and CO2 concentration on human responses was identified.


Saber-sheath malacic trachea remodeled and fixed into a normal shape by long-term placement and then removal of gianturco wire stent.
We report the case of a 59-year-old man who presented with major dyspnea due to saber-sheath malacic trachea associated with chronic pulmonary obstructive disease. The placement of a temporary tracheal stent alleviated his dyspnea very well; hence the stent was replaced with a Gianturco wire stent (Cook Cardiology, Bloomington, IN). However, this required removal due to wire-stent-related complications 2 years after the replacement. Surprisingly the trachea had been remodeled to a normal shape resulting in comfortable, functional respiratory status. A review of the literature reveals our case to be the first report of curing saber-sheath malacic trachea without leaving any prostheses or other foreign materials.


Fluorodeoxyglucose-positron emission tomography as a potential alternative tool for functional diagnosis of glycogen storage disease type I.
A 43-year-old woman with genetically confirmed glycogen storage disease type Ib was suspected to have left breast cancer. Fluorodeoxyglucose-positron emission tomography showed high fluorodeoxyglucose accumulation in the whole liver as well as left mammary gland. We consider that high fluorodeoxyglucose accumulation in the liver of patients with glycogen storage disease type I is caused by impaired glucose-6-phosphate metabolism due to the congenital deficiency of glucose-6-phosphatase activities in hepatocytes. This study describes fluorodeoxyglucose-positron emission tomography as a potential alternative tool to diagnose glycogen storage disease type I functionally.


Prevalence of and intention to change dietary and physical activity health risk behaviours.
Poor nutrition and insufficient physical activity contribute to high rates of obesity. Prevalence, intention to change and co-occurrence of four health risk behaviours (inadequate fruit and vegetables, excessive dietary fat, excessive sugary beverages and inadequate physical activity in comparison to public health recommendations) were investigated in an Australian population of working adults. Participants (n=105) completed sociodemographic and stage of change questionnaires. A subsample (n=40) were assessed twice to estimate test-retest repeatability. In the full sample, 73% were female, mean age was 33.8 years and mean BMI was 23.8 kg/m(2). Eighty-seven percent of participants consumed inadequate fruit and vegetables, 43% had excessive dietary fat, 42% had excessive sugary beverages and 29% had inadequate physical activity. The proportions intending to change each behaviour were 57%, 25%, 18% and 24%, respectively. Two-thirds exhibited multiple risk behaviours and 38% intended to change multiple risk behaviours. Fruit and vegetables and dietary fat were the most commonly paired risk behaviours (39%) and the pair most intended to change (19%). Occurrence of multiple risk behaviours was associated with being male (OR 3.10, 95% CI 1.06-9.03) or overweight/obese (OR 2.66, 95% CI 1.02-6.93). Targeting two risk behaviours, particularly fruit and vegetables and dietary fat, may be appropriate when designing health promotion programs in working populations.


Hepatoprotective effects of Wedelia calendulacea.
The alcoholic extract of whole plant Wedelia calendulacea exhibited protective activity against carbon tetrachloride-induced liver injury in vivo. The extract also increased the bile flow in rats suggesting a stimulation of liver secretory capacity. The minimum lethal dose was greater than 200 mg/kg p.o. in mice.


Axially Chiral N,N-Ligand-Promoted Pd-Catalyzed Enantioselective Allylic Amination and Alkylation.
An axially chiral N,N-ligand developed from a [1,1'-binaphthalene]-2,2'-diol (BINOL)-based skeleton and phenanthroline is found to be capable of promoting Pd-catalyzed asymmetric allylic amination and alkylation of allyl acetates. The reaction is compatible with cyclic and acyclic secondary amines, primary aliphatic amines, malononitrile, and dialkyl malonates, affording the corresponding chiral products in up to 99% yield and with up to >99% enantiomeric excess.