Lack of effect of oxytocin on the numbers of "synaptic" ribbons, cyclic guanosine monophosphate and serotonin N-acetyltransferase activity in organ-cultured pineals of three strains of rats.
In addition to the stimulating influence of the sympathetic system on the function of the mammalian pineal gland, neuropeptides such as neuropeptide Y, vasoactive intestinal polypeptide and arginine-vasopressin (AVP) are thought to function as modulators. Since AVP has been shown to influence pineal melatonin synthesis, the aim of the present study was to investigate the possible effects of the second hypothalamic nonapeptide oxytocin (OT), which likewise has been detected in the pineal gland. We therefore studied "synaptic" ribbon (SR) numbers, N-acetyltransferase (NAT) activity and the intracellular concentration of cyclic guanosine monophosphate (cGMP) following in vitro incubation of rat pineals in media containing OT (10(-5) M), noradrenaline (NA, 10(-5) M) or both NA and OT. Pineal glands were derived from rats of three different strains (Sprague-Dawley, Long-Evans and the AVP-deficient strain Brattleboro). Neither morphological nor biochemical analyses showed a difference between control and OT-incubated organs in any of the strains tested. In Brattleboro rats, but not in the other strains, noradrenaline slightly increased the number of SR which was not observed when NA and OT were combined. The addition of NA resulted in distinct augmentation of NAT activity and cGMP content, which were not affected by additional OT application. These results suggest that oxytocin is not crucially involved in the regulation of pineal gland function.


Determination of linear alkylbenzenes in fish tissue by gel permeation chromatography and gas chromatography-mass spectrometry.
A gel permeation chromatographic (GPC) procedure is described for separation of the long-chain linear alkylbenzenes (LABs) from fish muscle tissues. This technique was found to remove the matrix interference significantly and thereby improve the sensitivity of detection of LABs in the extracts. Gas chromatography-mass spectrometry (GC-MS) was then used to quantitate LABs in different species of fish and also fish from different locations on a transect from the outfalls from the Orange County Sanitation Districts, in the coastal waters of Southern California. The results are consistent with the proximity of the (sewage) source. The data, thus, show that LAB contents in fish tissues, especially that from white croaker (Genyonemus lineatus) are useful in assessing exposure to sewage residues in the marine waters. This method of concentrating LABs by GPC could be applicable to all other similar biological matrices.


Surface light chain phenotype in indolent lymphomas: lack of prognostic significance.
The indolent follicular and diffuse lymphomas are neoplasms of B-cell origin. In several other B-cell neoplastic disorders, including multiple myeloma, hairy cell leukemia, and chronic lymphocytic leukemia, the light chain isotype of the surface immunoglobulin has been reported to have prognostic significance. Patients with tumors expressing lambda light chains usually fare more poorly than those with kappa light chain-bearing tumours. We analyzed the clinical data and immunologic phenotype of 101 patients with indolent lymphoma. Eighty-nine of the 101 patients demonstrated surface immunoglobulin of only one light chain type (kappa-47, lambda-42). Patients in both groups were matched for known prognostic factors. There were no significant differences in disease-free survival or overall survival between the two groups or within histologic subtypes. These results indicate that the immunologic light chain phenotype in indolent lymphoma, unlike other B-cell neoplasms, is not a prognostic indicator of survival.


Exceptionally high selectivity in the separation of light hydrocarbons by adsorption on MIL-127(Fe) and on a (9,9) carbon nanotube.
Porous solids with channel sizes that are not much above the size of small hydrocarbons can yield extremely large adsorption selectivity. Our Grand Canonical Monte-Carlo simulations indicate exceptionally high selectivity for the separation of methane, ethane and propane from natural gas. At 250 K the C3H8/CH4 separation on MIL-127 at low pressure has a selectivity of more than 1000 and the C3H8/CH4 separation on CNT (9,9) is even above 2000. This is due to the strong molecule lattice interaction in narrow channels which leads to large enthalpies of adsorption. The Arrhenius law for the Henry coefficients is analysed in order to show that the effect is due to this enthalpy rather than to steric reasons.


Collagenoses and cutaneous manifestations of hepar diseases.
The authors discuss cutaneous manifestations of some systemic diseases (collagenoses) and their connection with diseases of liver cells.


Development of cervical intraepithelial lesions and cervical cancer is not influenced by SOD2 RS4880 polymorhism.
Some of the more than 200 known HPV types are essential for cervical cancer development, the third type of cancer most incident in the female population. However, for the malignant transformation occur, some cofactors are needed, as the reactive oxygen species (ROS), which can be neutralized by the antioxidant system. The SOD2 enzyme, encoded by the same name gene, is found in mitochondria and is part of the first line of defense against oxidative stress damage. Genetic polymorphisms can act by altering the efficiency of the enzyme, among which the most studied is the rs4880. Thus, the purpose of the present study was to evaluate the association of this polymorphism with HPV infection and the development of low and high grade squamous intraepithelial lesions (LSIL and HSIL) and cervical cancer, in 407 women attended by the public health system in Brazil. HPV detection in cervical secretion samples was carried out by polymerase chain reaction (PCR) and blood samples were used for polymorphism genotyping through PCR followed by restriction fragment length polymorphism (RFLP). PCR and restriction products were subjected to 10% polyacrylamide gel electrophoresis. HPV negative group (control) included 158 women and the HPV positive group (case) 249 women. The infected group was divided into No Lesion (n = 90), LSIL (n = 20), HSIL (n = 67) and cervical cancer (n = 72). The data found on socio-epidemiological characteristics and habits corroborated with data found in the literature. The distribution of genotypes in the control group was 51.9% women TC, 29.8% TT and 18.3% CC. In the case group, the distribution was 55.0% women TC, 26.1% TT and 18.9% CC. This is the first study evaluating the influence of SOD2 rs4880 polymorphism on HPV infection, the development of cervical intraepithelial lesions and cervical cancer in a Brazilian population, although additional studies are needed to corroborate the results.


Effects of high-speed power training on functional capacity and muscle performance in older women.
The purpose of the study was to examine the effects of 12 weeks high-speed power training on isometric contraction (handgrip strength), maximal strength (1RM), muscle power (walking velocity, counter movement jump and ball throwing) and functional tasks of the arm and leg muscles (sit-to-stand and get-up and go). Fifty-six older women were divided into an experimental group and a control group [EG, n=28, 62.5 (5.4) years; CG: n=28, 62.5 (4.3) years]. The EG was submitted to a high-speed power training that consisted of 40% of one repetition maximum (1<RM) to 75% of 1RM); 3 sets 4-12 reps, countermovement jump and medicine ball (1.5 kg) throwing. Over the 12-week training period, the EG significantly increased dynamic and isometric strength performance (57% to 61%), muscle power (range from 14% to 40%) (P<0.05) and function (P<0.05). No significant magnitudes of increase were observed in the CG. These data indicate that high-speed power training is an effective exercise approach leading to large gains in upper and lower extremity muscle performance and function capacity.


Carotenoids as chemopreventive agents.
Carotenoid pigments have been suggested as chemopreventive agents for reducing cancer risk in humans. In this article, the functions of carotenoids are reviewed, and the experimental evidence for carotenoid inhibition of mutagenicity, malignant transformation, and tumor formation is reviewed. It is suggested that the antioxidant function of carotenoids may explain their divergent effects as chemopreventive agents.


Principles and practices of obstetric airway management.
Although maternal mortality resulting from anesthesia is declining, airway causes predominate. Although there are many physiologic and nonphysiologic factors that contribute to potential difficulties when intubating parturients, whether or not the maternal airway is more difficult anatomically continues to be debatable. What is more certain, however, is that the situation is more complex than other settings. Vigilance, avoidance, and preparation continue to be key to management. In cases of unexpected difficulty, which likely are unavoidable, several rescue devices may be helpful.


Transfer of fatty acids from female seal blubber via milk to pup bladder.
Fatty acids were determined by gas chromatography followed by principal component analysis (PCA) and soft independent modelling of class analogy (SIMCA) in the blubber of 18 female grey seals, Halichoerus grypus, in their milk and in the blubber of their 1-week-old nursing pups. Large individual differences were observed in both blubber and milk content of fatty acids. The fatty acid composition of the milk was systematically different from the composition in maternal blubber, with higher relative amounts of the saturated acids, the monounsaturated with 20 carbon atoms and the n3 polyunsaturated, except 18:3n3. The composition of the fatty acids in the blubber of the pups was different from that of the milk. The same fatty acids that were enriched in the milk were depleted in the blubber of the pups. Therefore the fatty acid composition in the blubber of the pups was similar to that in the adults, although not identical. The results from this investigation imply that the composition of the fatty acids in the blubber of female seals and in the blubber of their pups cannot be determined directly by analysis of fatty acid composition of milk.


Comparative analysis of locking plate versus hook plate osteosynthesis of Neer type IIB lateral clavicle fractures.
Controversy exists on optimal operative treatment of vertically unstable Neer IIB lateral clavicle fractures. Aim of this study was to analyse and compare clinical and radiological results and complications of locking plate osteosynthesis (LPO) versus hook plate osteosynthesis (HPO) with acromioclavicular joint (ACJ) stabilization. The hypothesis was, that HPO would recreate coracoclavicular stability more effectively and potentially lead to a superior outcome. This retrospective, observational cohort study included 32 patients (19 HPO, 13 LPO) with a mean age of 44.1 ± 14.2 years at surgery. The mean follow-up period was 54.2 months (range 25.2-111.4 months). Besides standard radiography, bilateral coracoclavicular distances were assessed by means of preoperative and follow-up stress radiographs after implant removal. Clinical outcome measures included the Constant score (CS), the Oxford shoulder score (OSS), the subjective shoulder value (SSV) and the Taft score (TS). Bone union occurred in all but one patient and proved to occur delayed in five patients (15.6%). Radiographical healing required a mean of 4.2 ± 4.0 months irrespective of the type of osteosynthesis. At follow-up, mean coracoclavicular distance was increased by 34% (±36) without significant differences between both groups. HPO patients obtained a significantly lower TS (HPO: 9.5 ± 1.5 points, LPO: 11.1 ± 1.3 points; p = 0.005). Other mean score values did not differ (CS: 90.1 ± 7.4 points, OSS: 43.2 ± 9.2 points, SSV: 91.1 ± 14.7%). Sixteen patients (50.0%) experienced complications. Overall prevalence of complications was significantly higher in the HPO group (p = 0.014). Both HPO and LPO were equally effective in relation to restoration of vertical stability, overall functional outcome and fracture consolidation in treatment of Neer IIB fractures. Contrary to our hypothesis, HPO was not associated with superior recreation of the coracoclavicular distance. Considerable drawbacks of HPO were an inferior ACJ-specific outcome (Taft-Score) and a higher overall complication rate. Level of evidence IV.


Atrial sensor, remote monitoring and new anticoagulant drugs: Identification and treatment of a patient with unknown and asymptomatic atrial flutter.
This case report describes how new tools and technologies can drive a different approach in the management of arrhythmic patients. An unknown and asymptomatic atrial flutter was detected by the atrial sensor mounted in a single lead implantable cardioverter defibrillator. Moreover daily remote monitoring of the device allowed early notification and prompt clinical reaction. Anticoagulant therapy onset, radiofrequency ablation and the following anticoagulant therapy removal were driven by the device data transmissions.


Human spleen cells mediating natural killing: altered natural cytotoxicity of spleen effector cells from patients with carcinoma.
Spleen cells from eight patients with abdominal carcinoma and six patients undergoing major surgery for a variety of disease entities were assayed for natural cytotoxicity towards 51Cr-labelled K 562 target cells. Patients with abdominal cancer were shown to have relatively weak splenic natural cytotoxicity compared with the reactivity of effector cells from non-carcinoma patients. Nylon wool non-adherent spleen effector cells from cancer patients showed reduced cytolytic capacity compared with effector cells prepared from the spleens of other patients or peripheral blood mononuclear cells (PBMC) obtained from healthy individuals, whereas the splenic reactivity of non-cancer patients showed the same nylon wool separation profile as PBMC, high cytolytic activity being associated with nylon wool non-adherent effector cells. Splenic effector cell cytotoxicity from cancer and non-cancer patients was enhanced following exposure to human interferon, and inhibited by treatment with cholera toxin and simple sugars. Furthermore, fractionation of spleen cells on Percoll discontinuous density gradients demonstrated natural cytotoxic activity to reside predominantly in the low density cell fractions, similar to that found with NK cells from peripheral blood. Thus the properties described here for human cytotoxic spleen cells are similar to those described for peripheral blood NK cells, suggesting these two effector cell populations to be closely related, if not identical.


Increasing trend of endoscopic drainage utilization for the management of pancreatic pseudocyst: insights from a nationwide database.
The pancreatic pseudocyst (PP) is a type of fluid collection that typically develops as a delayed complication of acute pancreatitis. Drainage is indicated for symptomatic patients and/or associated complications, such as infection and bleeding. Drainage modalities include percutaneous, endoscopic, laparoscopic, and open drainage. This study aimed to assess trends in the utilization of different drainage modalities for treating PP from 2016 to 2020. The trends in mortality, mean length of hospital stay, and mean hospitalization costs were also assessed. The National Inpatient Sample database was used to obtain data. The variables were generated using International Classification of Diseases-10 diagnostic and procedural codes. Endoscopic drainage was the most commonly used drainage modality in 2018-2020, with an increasing trend over time (385 procedures in 2018 to 515 in 2020; p=0.003). This is associated with a decrease in the use of other drainage modalities. A decrease in the hospitalization cost for PP requiring drainage was also noted (29,318 United States dollar [USD] in 2016 to 18,087 USD in 2020, p<0.001). Endoscopic drainage is becoming the most commonly used modality for the treatment of PP in hospitals located in the US. This new trend is associated with decreasing hospitalization costs.


Differential stabilities of phosphorylated response regulator domains reflect functional roles of the yeast osmoregulatory SLN1 and SSK1 proteins.
Osmoregulation in Saccharomyces cerevisiae involves a multistep phosphorelay system requiring three proteins, SLN1, YPD1, and SSK1, that are related to bacterial two-component signaling proteins, in particular, those involved in regulating sporulation in Bacillus subtilis and anaerobic respiration in Escherichia coli. The SLN1-YPD1-SSK1 phosphorelay regulates a downstream mitogen-activated protein kinase cascade which ultimately controls the concentration of glycerol within the cell under hyperosmotic stress conditions. The C-terminal response regulator domains of SLN1 and SSK1 and full-length YPD1 have been overexpressed and purified from E. coli. A heterologous system consisting of acetyl phosphate, the bacterial chemotaxis response regulator CheY, and YPD1 has been developed as an efficient means of phosphorylating SLN1 and SSK1 in vitro. The homologous regulatory domains of SLN1 and SSK1 exhibit remarkably different phosphorylated half-lives, a finding that provides insight into the distinct roles that these phosphorylation-dependent regulatory domains play in the yeast osmosensory signal transduction pathway.


Ameloblastoma: a survey of 199 cases in the University of College Hospital, Ibadan, Nigeria.
In a study of occurrence of tumors of the jaw seen in the University College Hospital over a 24-year period, 199 cases of histologically diagnosed ameloblastoma were found. Notable features of these lesions were extreme size at presentation and high frequency of recurrence. Ameloblastoma ranks next in frequency to fibroosseous lesions and salivary gland tumors in this community. The incidence in men exceeds that of women. The mandible was the location in over 85 percent of the cases. Six cases were suspected to have turned malignant following multiple surgical operations.


[A method of preparing the results of biomedical research for statistical processing].
The method of preparing experimental findings based on their rationing which proceeds their statistical processing has been supposed. It has been shown that the supposed approach allows to find out real changes in the average values which are not revealed without rationing the initial findings.


Feeling rushed? Perceived time pressure impacts executive function and stress.
Executive function (EF) is critical to everyday life, but it can be undermined by adverse psychological states like stress and negative affect. For example, inadequate time to perform a task is a common stressor that can disrupt EF. Although the impact of actual time pressure on EF has been established, little is known about how self-generated, perceived time pressure (PTP) affects EF in the absence of objective time limits. We chose Eriksen's Flanker task as an index of cognitive inhibition, a key component of EF, and we varied the interval between successive trials, the inter-trial interval (ITI), to proxy PTP. This manipulation strongly impacted task performance: shrinking the ITI to increase PTP diminished cognitive inhibition and increased both stress and negative affect. Subsequently lengthening the ITI to decrease PTP reversed nearly all of these effects, except stress, which persisted. Multilevel linear regression modeling revealed that ITI and stress predicted inhibition, and exploratory mediation modeling suggested that stress mediates the relationship between ITI and inhibition. These findings validate perceived time pressure as an empirical stressor and demonstrate EF's sensitivity to changes in PTP.


Isolation of human platelet and red blood cell plasma membrane proteins by preparative detergent electrophoresis.
High resolution polyacrylamide gel electrophoretic techniques have been applied to the preparative isolation and analysis of plasma membrane proteins and glycoproteins from human platelets and red blood cells. The techniques presented allow relatively simple, direct, rapid and quantitative purification of a broad molecular weight range of membrane proteins, by means of continuous elution preparative gel electrophoresis of protein solubilized with sodium dodecyl sulfate. Spectrophotometric and fluorophotometric (fluorescamine) profiling, and high resolution gel electrophoretic analysis (SDS-acrylamide gradient slab gels, and gel electrofocusing) of eluted protein species indicate that purified membrane proteins of a broad molecular weight range may be obtained in a one step procedure, and in quantities and concentrations sufficient for further analytical or experimental procedures.


Orbital trapdoor fractures.
Orbital trapdoor fractures are commonly encountered in children. Awareness of trapdoor fractures is of particular importance. This is because early recognition and treatment are necessary to prevent permanent motility abnormities. In this article, we will provide a brief overview of orbital fractures. The clinical and radiographic features of trapdoor fractures will then be reviewed, followed by a discussion on their proper management.


Klotho-mediated changes in the expression of Atg13 alter formation of ULK1 complex and thus initiation of ER- and Golgi-stress response mediated autophagy.
In the previous paper of our group, we have demonstrated that one of the crucial factors involved in the crosstalk between autophagy and apoptosis is klotho protein. We have shown that klotho silencing in normal human fibroblasts intensifies lipopolysaccharide (LPS)-induced p-eIF2a-mediated stress of endoplasmic reticulum and thus leads to retardation of prosurvival autophagy and induction of apoptotic cell death. In this study, we have performed a detailed step-by-step analysis of autophagy flux-related genes' expression and endoplasmic reticulum and Golgi stress related pathways in order to determine the exact mechanistic event when autophagy is inhibited in klotho-deficient cells on account of apoptosis initiation. We provide evidence that klotho-silencing in LPS-treated cells results in differential course of ER- and Golgi-mediated stress response. Further, we show that in klotho-deficient cells formation of ULK1 complex is inhibited and thus autophagy initiation is blocked on the account of apoptosis activation, while in the control cells cytoprotective autophagy is activated. Finally, in klotho-deficient cells formation of ULK1 complex is prevented by downregulated expression of Atg13. Thus, this study suggests a novel targeting pathway for efficient elimination of autophagy-deficient cells.


Derived habitats of indoor microbes are associated with asthma symptoms in Chinese university dormitories.
Increasing evidence from the home environment indicates that indoor microbiome exposure is associated with asthma development. However, indoor microbiome composition can be highly diverse and dynamic, and thus current studies fail to produce consistent results. Chinese university dormitories are special high-density dwellings with similar building and occupants characteristics, which facilitate to disentangle the complex interactions between microbes, environmental characteristics and asthma. Settled air dust and floor dust was collected from 87 dormitory rooms in Shanxi University. Bacterial communities were characterized by 16 S rRNA amplicon sequencing. Students (n = 357) were surveyed for asthma symptoms and measured for fractional exhaled nitric oxide (FeNO). Asthma was not associated with the overall bacterial richness but associated with specific phylogenetic classes. Taxa richness and abundance in Clostridia, including Ruminococcus, Blautia, Clostridium and Subdoligranulum, were positively associated with asthma (p < 0.05), and these taxa were mainly derived from the human gut. Taxa richness in Alphaproteobacteria and Actinobacteria were marginally protectively associated with asthma, and these taxa were mainly derived from the outdoor environment. Bacterial richness and abundance were not associated with FeNO levels. Building age was associated with overall bacterial community variation in air and floor dust (p < 0.05), but not associated with the asthma-related microorganisms. Our data shows that taxa from different phylogenetic classes and derived habitats have different health effects, indicating the importance of incorporating phylogenetic and ecological concepts in revealing patterns in the microbiome asthma association analysis.


Feasibility of correlation mapping optical coherence tomography (cmOCT) for anti-spoof sub-surface fingerprinting.
We propose the use of correlation mapping optical coherence tomography (cmOCT) to deliver additional biometrics associated with the finger that could complement existing fingerprint technology for law enforcement applications. The current study extends the existing fingerprint paradigm by measuring additional biometrics associated with sub-surface finger tissue such as sub-surface fingerprints, sweat glands, and the pattern of the capillary bed to yield a user-friendly cost effective and anti-spoof multi-mode biometric solution associated with the finger. To our knowledge no other method has been able to capture sub-surface fingerprint, papillary pattern and horizontal vessel pattern in a single scan or to show the correspondence between these patterns in live adult human fingertip. Unlike many current technologies this approach incorporates 'liveness' testing by default. The ultimate output is a biometric module which is difficult to defeat and complements fingerprint scanners that currently are used in border control and law enforcement applications.


Full-length gonad transcriptome analysis of Amur sturgeon Dmrt family genes: identification, characterization, and expression patterns during gonadal differentiation.
The regulatory mechanisms that govern sex differentiation in sturgeon are still poorly understood. The doublesex and Mab-3-related transcription factor (Dmrt) gene family is known for its extensive roles in sex determination and differentiation across vertebrates. This study aimed to identify new members of sturgeon Dmrt family genes and core actors in the gonadal differentiation of Amur sturgeon. A full-length gonad transcriptome database was exploited to identify Dmrt gene orthologs. Analyses of phylogenetic relationships and selection pressure were performed, and tissue expression profiles and spatiotemporal expression patterns in gonads were then analyzed using real-time PCR. In total, five Dmrt family genes were identified from the full-length gonad transcriptome, including Dmrt2, DmrtA1, DmrtA2, DmrtB1a, and DmrtB1b. Phylogenetic analysis showed that these genes were clustered into clades corresponding to the doublesex/Mav-3 (DM) genes of vertebrates. Furthermore, the analysis of evolutionary selective pressure indicated that DmrtB1a and DmrtB1b were subject to positive selection, suggesting the existence of adaptive evolution in sturgeon. The extensive tissue expression profiling of each Dmrt family gene revealed typical characteristics. Remarkably, according to a spatiotemporal expression pattern analysis, in later stages, DmrtB1b expression increased in testes and was significantly higher in testes than in ovaries at 24 months after hatching (M) and 36 M. This study provides a genetic resource of full-length Dmrt family genes and increases the understanding of Dmrt functions in sex differentiation in sturgeon.


PEP-FOLD4: a pH-dependent force field for peptide structure prediction in aqueous solution.
Accurate and fast structure prediction of peptides of less 40 amino acids in aqueous solution has many biological applications, but their conformations are pH- and salt concentration-dependent. In this work, we present PEP-FOLD4 which goes one step beyond many machine-learning approaches, such as AlphaFold2, TrRosetta and RaptorX. Adding the Debye-Hueckel formalism for charged-charged side chain interactions to a Mie formalism for all intramolecular (backbone and side chain) interactions, PEP-FOLD4, based on a coarse-grained representation of the peptides, performs as well as machine-learning methods on well-structured peptides, but displays significant improvements for poly-charged peptides. PEP-FOLD4 is available at http://bioserv.rpbs.univ-paris-diderot.fr/services/PEP-FOLD4. This server is free and there is no login requirement.


Neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for extravesical urinary tract tumors.
A total of 11 patients with stage T2-4N0M0 extravesical tumors (prostate, prostatic urethra, urethra and ureter) received 1 to 4 cycles of neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin. Of 10 evaluable patients 4 (40 per cent) had downstaging to T0 disease with a clinical complete remission observed in 3 of 5 (60 per cent) with transitional cell tumors of the prostate and prostatic urethra. Four patients with urethral tumors of mixed or nontransitional histology failed to achieve a complete remission. The disease was staged pathologically in 4 patients: 1 had a partial remission and 3 had progression (all 4 had residual disease). Because therapy with methotrexate, vinblastine, doxorubicin and cisplatin induced only significant tumor regression of transitional cell elements of extravesical tumors and because it was ineffective against mixed histological tumors and in preventing new stage Tis lesions, surgical resection of such lesions is required.


Psychiatric inpatients subjected to physical restraint have a higher risk of deep vein thrombosis and aspiration pneumonia.
Physical restraint in clinical settings can lead to potentially lethal complications. Although this is a life-and-death issue, no comprehensive large-scale study relating medical complications to physical restraint has yet been performed. The 1308 psychiatric inpatients in our retrospective cohort study were categorized into two groups: a physical restraint group (those who had been subjected to physical restraint while hospitalized; n = 110) and a non-physical restraint group (those never subjected to physical restraint; n = 1198). We assessed differences between the two groups with respect to the occurrence of medical complications subsequent to restraint. To control for potentially confounding factors, linear discriminant regression analysis was used to identify whether physical restraint itself affected the occurrence of medical complications. The physical restraint group had a higher risk for deep vein thrombosis (P < .01, OR = 6.0, 95%CI: 2.4-13.9) and aspiration pneumonia (P < .01, OR = 4.1, 95%CI: 2.1-7.6) when compared with the non-physical restraint group. Even after controlling for potentially confounding factors, physical restraint substantially raised the risk of deep vein thrombosis and aspiration pneumonia (P < .01, P = .01, respectively). Although this study population was derived from a single psychiatric unit, physical restraint may lead to serious medical conditions. To avoid this unwanted consequence, the use of physical restraint should be minimized and physical therapy is highly recommended.


Effects of postural variation on anterior chamber depth in pseudoexfoliative eyes with normal intraocular pressure.
Pseudoexfoliation (PEX) is a condition characterized by widespread intraocular and systemic production and deposition of an abnormal fibrillar extracellular material. Zonular instability is frequently associated with PEX. Anterior chamber depth (ACD) and intraocular pressure (IOP) changes in normotensive eyes with PEX after prone position was investigated in this study. Thirty subjects with normotensive pseudoexfoliative eyes and 30 healthy control subjects were enrolled. None of the eyes had cataract or posterior synechia. Central ACD, axial length (AL), and IOP were measured 5 min after supine and prone positions by using A-scan ultrasonography and TonoPen. Mean ACD decreased from 2.89 ± 0.27 mm to 2.71 ± 0.23 mm in eyes with PEX and from 2.94 ± 0.25 mm to 2.84 ± 0.30 mm in normal eyes with postural change. The ACD decreased significantly in both group of eyes in prone position (p < 0.001 in PEX group, p = 0.005 in normal group), but the decrease in ACD in eyes with PEX was significantly greater than the decrease in normal control eyes (p = 0.03). Mean IOP was 16.9 ± 2.1 mmHg after supine position and 17.1 ± 2.04 mmHg after prone position in eyes with PEX, 16.1 ± 2.7 mmHg after supine position and 16.3 ± 2.6 mmHg after prone position in normal eyes. Postural changes in IOP and AL were not statistically significant in both groups of eyes (p = 0.096 in the PEX group and p = 0.484 in the normal group for IOP; p = 0.177 in the PEX group and p = 0.276 in the normal group for AL). The lens is more mobile in pseudoexfoliative eyes than normal eyes after supine to prone position. Although the ACD of pseuodoexfoliative eyes decreased statistically significantly after 5 min of prone position, IOP did not change significantly.


Pretransplantation interferon treatment and recurrence of hepatitis B virus infection after liver transplantation for hepatitis B-related end-stage liver disease.
Orthotopic liver transplantation in patients with hepatitis B-related cirrhosis is commonly complicated by reinfection with the hepatitis B virus, with rapidly progressive liver disease and poor survival rate. We assessed the efficacy of prior therapy with recombinant interferon-alpha on the prevention of posttransplantation hepatitis B virus reinfection. Twenty-two patients with hepatitis B-related cirrhosis waiting for liver transplantation received 3 MU (decreased to 1.5 MU in cases of intolerance) of recombinant interferon-alpha until transplantation. The rates of posttransplantation hepatitis B virus reinfection and survival in this group were compared with those in a group of 26 patients previously given transplants for the same disease but not given interferon therapy. The same protocol of HBs antibody passive immunoprophylaxis was applied after transplantation in both groups. Recombinant interferon-alpha was administered for 14 +/- 7 wk. The treatment had an antiviral effect, with disappearance of serum hepatitis B virus DNA in seven of the eight patients initially positive for hepatitis B virus DNA and disappearance of HBeAg in two of the three patients initially positive for HBeAg. Serum hepatitis B virus DNA remained detectable with polymerase chain reaction at transplantation in 56% of the interferon-treated patients. After transplantation, hepatitis B virus reinfection was more frequent in polymerase chain reaction-positive than in polymerase chain reaction-negative patients (78% vs. 17%, p < 0.05). One patient's condition deteriorated during interferon treatment; this patient was not given a transplant. Two patients (in whom hepatitis B virus DNA disappeared from serum) improved so markedly during treatment that they were not given transplants.(ABSTRACT TRUNCATED AT 250 WORDS)


How clocks and hormones act in concert to control the timing of insect development.
During the last century, insect model systems have provided fascinating insights into the endocrinology and developmental biology of all animals. During the insect life cycle, molts and metamorphosis delineate transitions from one developmental stage to the next. In most insects, pulses of the steroid hormone ecdysone drive these developmental transitions by activating signaling cascades in target tissues. In holometabolous insects, ecdysone triggers metamorphosis, the remarkable remodeling of an immature larva into a sexually mature adult. The input from another developmental hormone, juvenile hormone (JH), is required to repress metamorphosis by promoting juvenile fates until the larva has acquired sufficient nutrients to survive metamorphosis. Ecdysone and JH act together as key endocrine timers to precisely control the onset of developmental transitions such as the molts, pupation, or eclosion. In this review, we will focus on the role of the endocrine system and the circadian clock, both individually and together, in temporally regulating insect development. Since this is not a coherent field, we will review recent developments that serve as examples to illuminate this complex topic. First, we will consider studies conducted in Rhodnius that revealed how circadian pathways exert temporal control over the production and release of ecdysone. We will then take a look at molecular and genetic data that revealed the presence of two circadian clocks, located in the brain and the prothoracic gland, that regulate eclosion rhythms in Drosophila. In this context, we will also review recent developments that examined how the ecdysone hierarchy delays the differentiation of the crustacean cardioactive peptide (CCAP) neurons, an event that is critical for the timing of ecdysis and eclosion. Finally, we will discuss some recent findings that transformed our understanding of JH function.


Isolation of luminal and antiluminal membranes from dog kidney cortex.
Luminal (brush border) and antiluminal (basal-lateral) membranes were isolated from canine renal cortex. The enzyme marker for luminal membrane, alkaline phosphatase was enhanced 19-fold and the antiluminal enzyme marker, (Na+ + K+)-ATPase, was enhanced 22-fold in their respective membrane preparation, while the amount of cross contamination was minimal. Contamination of these preparations by enzyme markers for lysosomes, endoplasmic reticulum and mitochondria was also low. Routinely, more than 50 mg membrane protein was isolated for each membrane. Electron micrographs showed that the membranes were uniform in size, appearance, and vesicular in nature. An examination of the orientation of these membranes showed that 76.5% of the antiluminal membranes and 86% of the luminal membranes were right-side out.


Determination of sulfadimethoxine in milk with aptamer-functionalized Fe3 O4 /graphene oxide as magnetic solid-phase extraction adsorbent prior to HPLC.
An aptamer (Apt) functionalized magnetic material was prepared by covalently link Apt to Fe3 O4 /graphene oxide (Fe3 O4 /GO) composite by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide, and then characterized by FTIR spectroscopy, X-ray diffraction, and vibration sample magnetometry. The obtained composite of Fe3 O4 /GO/Apt was employed as magnetic solid-phase extraction adsorbent for the selective preconcentration of sulfadimethoxine prior to analysis by high-performance liquid chromatography. Under the optimal conditions (sample pH of 4.0, sorbent dosage of 20 mg, extraction time of 3 h, and methanol-5% acetic acid solution as eluent), a good linear relationship was obtained between the peak area and concentration of sulfadimethoxine in the range of 5.0 to 1500.0 µg/L with correlation coefficient of 0.9997. The limit of detection (S/N = 3) was 3.3 µg/L. The developed method was successfully applied to the analysis of sulfadimethoxine in milk with recoveries in the range of 75.9-92.3% and relative standard deviations less than 8.1%. The adsorption mechanism of Fe3 O4 /GO/Apt toward sulfadimethoxine was studied through the adsorption kinetics and adsorption isotherms, and the results show that the adsorption process fits well with the pseudo-second-order kinetic model and the adsorbate on Fe3 O4 /GO/Apt is multilayer and heterogeneous.


A comparison of the central and peripheral antimuscarinic effects of atropine and methylatropine injected systemically and into the cerebral ventricles.
We compared the relative abilities of atropine sulfate and methylatropine, injected i.v. and into the cerebral ventricles (icv), to block pharmacological responses mediated through central and peripheral muscarinic receptors. The hypotensive response to i.v. injection of acetylcholine (peripheral muscarinic receptors) was inhibited 50% by i.v. injection of 14.3 nmol (5.5 micrograms)/kg methylatropine and 147.8n molar equivalents (50 micrograms)/kg atropine sulfate. A similar degree of inhibition followed icv injection of 49.4 nmol/kg methylatropine and 384.2 nmol equivalents/kg atropine sulfate, indicating significant leakage out of the ventricular space. The pressor response to icv injection of neostigmine (central muscarinic receptors) also was inhibited more effectively by icv methylatropine than by atropine sulfate. Methylatropine was not effective in blocking central muscarinic receptors when injected i.v.


[X-ray dose reduction in examination of infant's hip with image-intensifier-fluoroscopy-system (author's transl)].
An image intensifier--70mm camera--fluoroscopy system combined with a conventional X-ray tube is used for routine examination of the infant's hip. The high quality of 85% of these 70mm exposures makes immediate diagnostic interpretation possible. An even higher percentage can be achieved by most exact positioning of the patients. Apart from the radiation protection of the gonades, the X-ray skin dose of the primary beam is reduced by 90-95% compared with full size radiography using film screen combinations. This exposure technique can certainly be used not only for the examination of the infant's hip.


A Three Dimensional Calderon-Based Method for EIT on the Cylindrical Geometry.
Electrical impedance tomography (EIT) is an imaging modality in which voltage data arising from currents applied on the boundary are used to reconstruct the conductivity distribution in the interior. This paper provides a novel direct (noniterative) 3-D reconstruction algorithm for EIT in the cylindrical geometry. The algorithm is based on Calderón's method [Calderón, 1980], and is implemented for data collected on two or four rows of electrodes on the boundary of a cylinder. The effectiveness of the method to localize inhomogeneities in the plane of the electrodes and in the z-direction is demonstrated on simulated and experimental data. The results from simulated and experimental data show that the method is effective for distinguishing in-plane and nearby out-of-plane inhomogeneities with good spatial resolution in the vertical z direction with computational efficiency.


Necrotizing enterocolitis in neonates fed human milk.
The incidence of necrotizing enterocolitis encountered in neonates fed only refrigerated human milk was comparable to that in infants fed milk and isotonic formula or isotonic formula alone. The infants fed human milk were significantly (P less than 0.05) smaller, less mature, had lower Apgar scores, and were fed later than the formula-fed infants. The mean age of onset and time between first feeding and onset of NEC was similar among the three groups. These data indicate that refrigerated human milk was not effective in lowering the incidence of NEC. Possible explanations for the occurrence of NEC in neonates fed human milk include: (1) the introduction of a pathogen via contaminated milk; (2) inadequate maternal antigenic stimulation by the neonatal gastrointestinal flora; and (3) adverse affects of storage on cell number and function.


Predictive eye saccades are different from visually triggered saccades.
The metrics of eye saccades in response to random and predictable target motion were determined in 8 normal young subjects. The peak velocity of predictive saccades (PS) was significantly reduced when compared with randomly elicited saccades (RS) of equal amplitude. Saccadic gain (initial saccadic amplitude/target amplitude) was also decreased in PS. Saccadic inaccuracy was extremely frequent in PS and, in contrast to RS, it was independent of target amplitude displacement. These stimulus-dependent changes in saccadic characteristics may reflect activation of the saccadic pontine generators by different supranuclear pathways.


Anatomical implications of the subvastus approach on major vascular injury during a distal femoral osteotomy: a computed tomographic venography study.
This study evaluated major vascular injury risk in distal femoral osteotomy (DFO) via the subvastus approach and examined the relationship between the posterior border of the vastus medialis (VM) and the superficial femoral artery (SFA) and vein (SFV). Eighty limbs from 80 patients were evaluated using lower extremity computed tomographic venography. The positional relationship between the VM, SFA, and SFV was evaluated by measuring the angle between each structure and the horizontal reference point (VMA: VM angle, FAA (femoral arterial angle), FVA (femoral venous angle) and the distance between VM and the SFA and SFV (VMAD: VM-arterial distance, VMVD: VM-venous distance) in each axial slice (0/10/20/30/40 mm) proximal to the level of the superior patellar margin. The proximity of the posterior border of the VM and the SFA/SFV as a vertical distance, measured between the slice of the superior border of the patella and the slice where the posterior border of the VM contacted the SFA was evaluated. Single and multiple regression analyses were performed using the vertical distance as the objective variable. As the slice shifted proximally, the VMA significantly increased (24.9 ± 8.5, 36.3 ± 8.8, 47.4 ± 11.8, 59.9 ± 14, 70.3 ± 13.7 degrees, respectively, p < 0.001 between all slices) and moved posteromedially from a medial direction. FAA (94.2 ± 7, 86.9 ± 9.2, 78.4 ± 9.7, 71.4 ± 9.8, 66.6 ± 10.5 degree, respectively, p < 0.001 between all slices) and FVA (100.6 ± 4.9, 98.3 ± 5.9, 93.7 ± 7.5, 88 ± 9.2, 81.1 ± 10.5 degrees, respectively, p < 0.001 between all slices) decreased and moved from a posterolateral to a posteromedial direction, while VMAD (35.4 ± 7.8, 24.1 ± 7.3, 14.3 ± 6, 8.4 ± 7, 6.2 ± 6.3 mm, respectively, p < 0.001 between all slices) and VMVD significantly decreased (42.7 ± 7.3, 32 ± 7.4, 22.4 ± 6.8, 14.5 ± 10.6, 8.7 ± 7.1 mm, respectively, p < 0.001 between all slices). The average vertical distance was 36 ± 9.3 mm (range 18.6-61.5 mm). The body height and the patellar length significantly affected the vertical distance. The posterior border of the VM shifted posteromedially from distal to proximal and contacted the SFA at an average of 36 mm from the suprapatellar border. Surgeons should be aware of the risk of major vascular injury during exposure and osteotomy. Case series, Level IV.


Congenital bladder duplication and diverticulum.
Evaluation of urinary infection in a 5-month-old male infant revealed duplication of the prostatic urethra and bladder. Associated anomalies were a right bladder diverticulum, left vesicoureteral reflux and bowel duplication.


Bone loss in adult offspring induced by low-dose exposure to teratogens.
Maternal malnutrition during pregnancy was shown by numerous studies to result in the birth of offspring exhibiting altered bone characteristics, which are indicative of bone loss. We hypothesized that not only maternal malnutrition but also some developmental toxicants (teratogens) given at a dose inducing neither structural anomalies nor growth retardation can detrimentally affect skeletal health in adult offspring. To check this hypothesis, pregnant mice were exposed to a single injection of 5-aza-2-deoxycytidine (5-AZA) (a teratogen capable of inducing phocomelia of the hind limbs) at a sub-threshold teratogenic dose. Micro-computed tomography scanning revealed that femora of 5-month-old male offspring exposed in uterus to 5-AZA had trabecular microarchitecture indicative of bone loss. Furthermore, exposure to 5-AZA increased the susceptibility of offspring to postnatal chronic mild stress, which has been shown to induce bone loss in mice. While exploring possible mechanisms underlying this phenomenon, we observed that the expression of some microRNAs, which have been demonstrated as regulators of key osteoblastogenic genes, was altered in hind limb buds of embryos exposed to 5-AZA. Furthermore, the expression of receptor activator of nuclear factor kappa B ligand (RANKL) in femoral stromal/osteoblastic cells of 5-month-old offspring of 5-AZA-treated females was found to be increased. Collectively, this study implies for the first time that single low-dose exposure to a teratogen can induce bone loss in adult offspring, possibly via alteration of embryonic microRNAs and RANKL expression.


Reverse transcriptases from bacterial retrons require specific secondary structures at the 5'-end of the template for the cDNA priming reaction.
Multicopy single-stranded DNA (msDNA) is a peculiar molecule consisting of a single-stranded DNA that is branched out from an internal G residue of an RNA molecule (msdRNA) via a 2',5'-phosphodiester linkage. The genetic unit required for msDNA synthesis is designated "retron" and consists of msr (a gene for msdRNA), msd (a gene for msDNA), and a gene for reverse transcriptase (RT) in a single operon. To date, four different msDNAs have been isolated from Escherichia coli. They do not share any primary sequences in either RNA or DNA. To elucidate the specificity of bacterial RT for msDNA synthesis, the msr-msd region from retron-Ec67 was introduced into E. coli cells producing RT-Ec73, or the msr-msd region from retron-Ec73 into E. coli cells producing RT-Ec67. In both cases, msDNA was not synthesized. However, when the msdRNA coding regions (msr) for retron-Ec67 and -Ec73 were mutually exchanged and the chimeric genes were introduced into E. coli cells producing either RT-Ec67 or RT-Ec73, it was thus found that msDNA was produced only when msr and RT were from the same retron. Requirement of the msr region for msDNA synthesis by RT was further investigated by mutations in the msr region for retron-Ec67. These analyses revealed that there is a strict requirement for specific primary sequences as well as the secondary structure in msdRNA. This finding is discussed in relationship to the mechanism of the priming reaction of cDNA synthesis by eukaryotic retroviral RTs using tRNAs.


A 3D-Printed Assemblable Bespoke Scaffold as a Versatile Microcryogel Carrier for Site-Specific Regenerative Medicine.
Advances in additive manufacturing have led to diverse patient-specific implant designs utilizing computed tomography, but this requires intensive work and financial implications. Here, Digital Light Processing is used to fabricate a hive-structured assemblable bespoke scaffold (HIVE). HIVE can be manually assembled in any shape/size with ease, so a surgeon can create a scaffold that will best fit a defect before implantation. Simultaneously, it can have site-specific treatments by working as a carrier filled with microcryogels (MC) incorporating different biological factors in different pockets of HIVE. After characterization, possible site-specific applications are investigated by utilizing HIVE as a versatile carrier with incorporated treatments such as growth factors (GF), bioceramic, or cells. HIVE as a GF-carrier shows a controlled release of bone morphogenetic protein/vascular endothelial growth factor (BMP/VEGF) and induced osteogenesis/angiogenesis from human mesenchymal stem cells (hMSC)/human umbilical vein endothelial cells (HUVECs). Furthermore, as a bioceramic-carrier, HIVE demonstrates enhanced mineralization and osteogenesis, and as a HUVEC carrier, it upregulates both osteogenic and angiogenic gene expression of hMSCs. HIVE with different combinations of MCs yields a distinct local effect and successful cell migration is confirmed within assembled HIVEs. Finally, an in vivo rat subcutaneous implantation demonstrates site-specific osteogenesis and angiogenesis.


Disordered eating in collegiate English equestrian athletes in aesthetic and nonaesthetic disciplines.
Little is known about the rates of disordered eating behaviors in the athletes who compete in the disciplines that comprise collegiate English Equestrian sports. Importantly, in some subdisciplines, riders' scores depend upon judges' assessment of their appearance while riding, rather than upon solely objective measures such as time to complete a course. The purpose of the present research was to 1) assess the current rate of disordered eating behaviors in college equestrian athletes, 2) test whether certain disciplines of English riding (i.e., those that focus on aesthetics or non-aesthetics) at the collegiate level have higher rates of disordered eating behaviors, and 3) test whether these athletes face different pressures for appearance and weight if they specialize in aesthetic riding disciplines. English equestrian student athletes from across the United States (N = 330; 97 % female) and from the following disciplines were surveyed: equitation (aesthetic), dressage (aesthetic), hunters (aesthetic), jumpers (non-aesthetic), and eventing (non-aesthetic). The results suggest a high prevalence of disordered eating in the sport (35 % met cut off for disordered eating using the EAT-26). Findings suggest similar rates of disordered eating behaviors between the aesthetic and non-aesthetic disciplines. Findings also indicate that student athletes in aesthetic disciplines were much more likely to say that they were weighed by coaches and pressured to lose weight. Thus, the current study lends empirical support to the notion that coaches can be a source of pressure for these athletes. Issues of addressing disordered eating in coaching and future research are discussed.


A reevaluation of midbrain and diencephalic projections to the inferior olive in rat with particular reference to the rubro-olivary pathway.
Projections from the midbrain and caudal diencephalon to the inferior olivary nucleus (ION) in the rat were investigated by using anterograde and retrograde tracing techniques. Particular attention was directed to studying the projection from the red nucleus (RN) to the ION. Tritiated leucine was stereotaxically injected into the RN in six animals. The injection sites and the portion of the medulla containing the ION were processed for autoradiography. In three cases, the injections were largely confined to the RN. In these instances, no terminal labeling was noted in the ION. In the other three animals, the injections spread beyond the RN to include, in one or another of the rats, such areas as the mesencephalic reticular formation (MRF) between the RN and the periaqueductal gray (PAG), the region around the fasciculus retroflexus (FR), the prerubral area, the MRF dorsolateral to the RN, or the region dorsal to the medial geniculate body. In these animals, terminal labeling was observed ipsilaterally in the ION, chiefly in the caudal one-half of the medial accessory olive and in the dorsal lamella and lateral bend of the principal olive. Retrograde transport of lectin-conjugated horseradish peroxidase (WGA-HRP) or the fluorescent dye fast blue (FB), injected into the ION, was used to localize regions in the midbrain and caudal diencephalon containing neurons which project to the inferior olive. Following WGA-HRP injections into the ION, retrogradely labeled neurons were found in the ipsilateral ventral PAG, the MRF between the PAG and the RN, the MRF dorsolateral to the RN, and the area dorsal to the medial geniculate body. Large numbers of heavily labeled neurons were found in the area surrounding the FR. No labeled cells were noted in the RN or the nucleus of Darkschewitsch (ND). Subsequent to FB injections into the ION, fluorescent neurons were observed in the same regions which contained HRP-labeled neurons in the experiments using the enzyme as a tracer. Additionally, very small numbers of FB-labeled neurons were found in the RN and the ND. These results indicate that, in the rat, descending input from the midbrain and caudal diencephalon to the ION arises chiefly from a medially located column of neurons extending from the level of the rostral RN to the region of the FR. Little, if any, input to the ION is derived from the ND or RN in this species, unlike the cat, in which a substantial projection to the ION arises from the ND and the RN.


Ex Vivo Human Neutrophil Swarming Against Live Microbial Targets.
Neutrophils often communicate with each other and coordinate their actions to seal off large sites of injury and infection that individual neutrophils could not cover. The concerted actions of neutrophils are essential for the expeditious protection of healthy tissues from wounds and microbes. These processes, collectively known as swarming, are typically studied in vivo in mice. However, these studies are low throughput and their relevance to human disease is limited. Recently, new tools have been developed for the study of human neutrophil swarming ex vivo. The emergent microscale swarming assays are providing significant insights into the molecular mediators of swarming. By enabling the direct study of human cells, these assays also shed new light on human diseases and host responses against infections. Here, we describe a robust technique for manufacturing microscale swarming arrays with live microbial targets (e.g., clusters of Candida albicans). These arrays allow for the direct, precise, and efficient interrogation of the antimicrobial functions of human swarming against a variety of targets.


H-phosphonate derivatives as novel peptide deformylase inhibitors.
Peptide deformylase catalyzes the removal of the N-terminal formyl group from nascent polypeptides during prokaryotic protein maturation and is essential for bacterial survival. Its absence from eukaryotic organisms makes it an attractive target for designing novel antibacterial agents. Peptidyl H-phosphonates were synthesized and shown to be competitive inhibitors of the deformylase.


Methuosis: nonapoptotic cell death associated with vacuolization of macropinosome and endosome compartments.
Apoptosis is the most widely recognized form of physiological programmed cell death. During the past three decades, various nonapoptotic forms of cell death have gained increasing attention, largely because of their potential importance in pathological processes, toxicology, and cancer therapy. A recent addition to the panoply of cell death phenotypes is methuosis. The neologism is derived from the Greek methuo (to drink to intoxication) because the hallmark of this form of cell death is displacement of the cytoplasm by large fluid-filled vacuoles derived from macropinosomes. The demise of the cell resembles many forms of necrosis, insofar as there is a loss of metabolic capacity and plasma membrane integrity, without the cell shrinkage and nuclear fragmentation associated with apoptosis. Methuosis was initially defined in glioblastoma cells after ectopic expression of activated Ras, but recent reports have described small molecules that can induce the features of methuosis in a broad spectrum of cancer cells, including those that are resistant to conventional apoptosis-inducing drugs. This review summarizes the available information about the distinguishing morphological characteristics and underlying mechanisms of methuosis. We compare and contrast methuosis with other cytopathological conditions in which accumulation of clear cytoplasmic vacuoles is a prominent feature. Finally, we highlight key questions that need to be answered to determine whether methuosis truly represents a unique form of regulated cell death.


Flexible sensor based on carbon nanofibers with multifunctional sensing features.
Herein, we present the fabrication and characterization of a flexible gas sensor based on carbon nanofibers. The sensing device is composed of interdigitated silver electrodes deposited by inkjet printing on Kapton substrates, subsequently coated with carbon nanofibers as sensing element. Gas sensing response to CO, NH3 and humidity has been characterized in detail. Thermal, mechanical and electromagnetic radiation effects have also been studied and discussed from the point of view of the cross-sensitivity. The obtained results open the door for a new generation of flexible sensors with multifunctional sensing features, which are producible with scalable techniques based on low cost nanomaterials.


Mercury speciation and mobility in mine wastes from mercury mines in China.
Mercury (Hg) speciation and mobility were determined in calcines and waste rocks collected from 9 Hg mines in China. Total Hg (THg) concentrations in the mine wastes varied widely in different Hg mines (with a range of 0.369 to 2,620 mg kg(-1)). Cinnabar is the dominant form of Hg in the mine wastes. However, Hg(2+) and Hg(0) concentrations in the calcines were significantly higher than these in the waste rocks, which suggested the retorting can produce large amounts of by-product Hg compounds. The THg and Hg(0) concentrations in certain mine wastes exceeded soil guidelines recommended by US Environmental Protection Agency; while total soluble Hg concentrations of leachates in certain mine wastes exceeded National Surface Water Quality Standard of China. Mine wastes are important Hg pollution sources to the aquatic ecosystem and atmosphere.


Endothelin-1 as a potential marker of melatonin's therapeutic effects in smoking-induced vasculopathy.
Smoking is a significant independent risk factor for cardiovascular disease. Among the chemicals present in the cigarette smoke, nicotine is responsible for much of the damage; it induces marked vessel morphological dysfunction and vasoconstriction. Unfortunately, pharmacological or behavioural treatment is not useful against cigarette smoking. The purpose of this study is to test, in experimental conditions, the therapeutic ability of exogenous melatonin administered after smoking-induced vasculopathy and to evaluate the targets of its effects. Nicotine was orally administered for 28 days. Thereafter, the rats were orally treated with melatonin for another 28 days. Vessel damage, an important vasoconstrictor peptide (endothelin-1) and the oxidative stress markers were analysed. Nicotine treatment induced marked endothelial damage and an obvious vasoconstriction in the aorta as evaluated by an increased endothelin-1 (ET-1) expression. These alterations were correlated with a reduction of endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) and with increases of heat shock protein (Hsp70) and inducible nitric oxide synthase (iNOS) activities. Melatonin not only improved the impairment of endothelial-dependent relaxation, but also induced the increase of eNOS and SOD and the reduction of iNOS and Hsp70. The findings indicate that nicotine is associated with an elevated synthesis of the vasoconstrictor peptide (ET-1); it also induces a reduction of nitric oxide-mediated vasodilatation (eNOS) and promotes oxidative stress in the vessel wall. We propose that melatonin should be considered as a therapeutic intervention for smokers since it reduces vasoconstriction and oxidative stress and improves endothelial physiology.


Physiological and growth responses of Centaurea maculosa (Asteraceae) to root herbivory under varying levels of interspecific plant competition and soil nitrogen availability.
Centaurea maculosa seedlings were grown in pots to study the effects of root herbivory by Agapeta zoegana L. (Lep.: Cochylidae) and Cyphocleonus achates Fahr. (Col.: Curculionidae), grass competition and nitrogen shortage (each present or absent), using a full factorial design. The aims of the study were to analyse the impact of root herbivory on plant growth, resource allocation and physiological processes, and to test if these plant responses to herbivory were influenced by plant competition and nitrogen availability. The two root herbivores differed markedly in their impact on plant growth. While feeding by the moth A. zoegana in the root cortex had no effect on shoot and root mass, feeding by the weevil C. achates in the central vascular tissue greatly reduced shoot mass, but not root mass, leading to a reduced shoot/root ratio. The absence of significant effects of the two herbivores on root biomass, despite considerable consumption, indicates that compensatory root growth occurred. Competition with grass affected plant growth more than herbivory and nutrient status, resulting in reduced shoot and root growth, and number of leaves. Nitrogen shortage did not affect plant growth directly but greatly influenced the compensatory capacity of Centaurea maculosa to root herbivory. Under high nitrogen conditions, shoot biomass of plants infested by the weevil was reduced by 30% compared with uninfested plants. However, under poor nitrogen conditions a 63% reduction was observed compared with corresponding controls. Root herbivory was the most important stress factor affecting plant physiology. Besides a relative increase in biomass allocation to the roots, infested plants also showed a significant increase in nitrogen concentration in the roots and a concomitant reduction in leaf nitrogen concentration, reflecting a redirection of the nitrogen to the stronger sink. The level of fructans was greatly reduced in the roots after herbivore feeding. This is thought to be a consequence of their mobilisation to support compensatory root growth. A preliminary model linking the effects of these root herbivores to the physiological processes of C. maculosa is presented.


Metabolic Alterations in a Drosophila Model of Parkinson's Disease Based on DJ-1 Deficiency.
Parkinson's disease (PD) is the second-most common neurodegenerative disorder, whose physiopathology is still unclear. Moreover, there is an urgent need to discover new biomarkers and therapeutic targets to facilitate its diagnosis and treatment. Previous studies performed in PD models and samples from PD patients already demonstrated that metabolic alterations are associated with this disease. In this context, the aim of this study is to provide a better understanding of metabolic disturbances underlying PD pathogenesis. To achieve this goal, we used a Drosophila PD model based on inactivation of the DJ-1β gene (ortholog of human DJ-1). Metabolomic analyses were performed in 1-day-old and 15-day-old DJ-1β mutants and control flies using 1H nuclear magnetic resonance spectroscopy, combined with expression and enzymatic activity assays of proteins implicated in altered pathways. Our results showed that the PD model flies exhibited protein metabolism alterations, a shift fromthe tricarboxylic acid cycle to glycolytic pathway to obtain ATP, together with an increase in the expression of some urea cycle enzymes. Thus, these metabolic changes could contribute to PD pathogenesis and might constitute possible therapeutic targets and/or biomarkers for this disease.


Clinical and social predictors of application for social security disability insurance by workers' compensation claimants with low back pain.
The objective of this study was to identify clinical and social predictors of application for Social Security Disability Insurance (SSDI) in workers' compensation claimants with low back pain. Archival and interview data were analyzed for 1372 Missouri claimants who were, on average, nearly 42 months postinjury. Two hundred sixty-five (19.3%) claimants were receiving SSDI (8.0%) or had applied for SSDI (11.3%). Logistic regression indicated that black race, older age, herniated disc diagnosis, surgery, and longer time since injury were associated with increased odds of SSDI. Higher preinjury wage, more education, and higher satisfaction with medical treatment and/or treatment by employer were associated with decreased odds of SSDI. Application for SSDI among claimants with occupational low back pain is associated with social factors like race, satisfaction, and socioeconomics as well as clinical factors like diagnosis and surgery.


Skepticism and learning difficulties in a digital environment at the Bachelor's and Master's levels: are preconceptions valid?
There are a number of beliefs and preconceptions concerning online learning in university digital environment. Are they valid? The study aimed to compare perceived learning experiences of students who completed the e-course with flipped design, to identify the set of opinions common to the majority of students and assess differences of perceived experiences between graduate and undergraduate students. The target groups were students at the Bachelor's (N = 183) and Master's (N = 161) levels participating in e-courses in mathematical methods in psychological and educational researches (N = 344 in total). The quasi-experimental study was conducted at the Moscow State University of Psychology and Education (MSUPE). Using cluster analysis method for each of the 5 thematic groups of the survey points, 2 clusters were identified, typical opinions spectrum of the respondents majority was characterized, and differences between learners at the Bachelor's and Master's levels in these clusters were estimated. (1) For only one topic regarding students' learning independence, interaction and engagement, the share of master's programs students in a large cluster significantly prevails, for the remaining 4 topics there were no differences: ca 70-75% of both levels students belonged to a large cluster. (2) Most students confirm the benefits of e-courses, no substantial difficulties were identified. This contradicts the preconception that older Master's level students more troublesome adapt to digital environment learning, experience more difficulties and are more critical. (3) Most respondents at both levels show a positive motivation for learning in a digital environment. This contradicts the preconception that graduate students are more skeptical of e-learning. (4) Most students confirm the interactive style of blended sessions' activities, i.e., mutual assistance and interaction with classmates and the instructor, but they more often perceive deficiency of personal contacts with the instructor and do not agree to replace face-to-face sessions with webinars and communication on forums. This set of opinions is more characteristic of graduate students. Perhaps this is partly a reflection of main beliefs of instructors supported the full-time education. (5) Almost all students find the e-course informative and practically useful. (6) Most of the respondents are characterized by careful answers to points concerning the use of dishonest strategies in online learning and the belief that dishonest strategies using is inevitable. Perhaps this is a reflection of their life experiences or an excuse for their own dishonest strategies. This problem requires further investigation.


Testing the critical window of estradiol replacement on gene expression of vasopressin, oxytocin, and their receptors, in the hypothalamus of aging female rats.
The current study tested the "critical window" hypothesis of menopause that postulates that the timing and duration of hormone treatment determine their potential outcomes. Our focus was genes in the rat hypothalamus involved in social and affiliative behaviors that change with aging and/or estradiol (E2): Avp, Avpr1a, Oxt, Oxtr, and Esr2 in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). Rats were reproductively mature or aging adults, ovariectomized, given E2 or vehicle treatment of different durations, with or without a post-ovariectomy delay. Our hypothesis was that age-related changes in gene expression are mitigated by E2 treatments. Contrary to this, PVN Oxtr increased with E2, and Avpr1a increased with age. In the SON, Avpr1a increased with age, Oxtr with age and timing, and Avp was altered by duration. Thus, chronological age and E2 have independent actions on gene expression, with the "critical window" hypothesis supported by the observed timing and duration effects.


A Combination of Beta-Blockade and Calcium Channel Blockade Leading to Bradycardia, Renal Failure, Atrioventricular Blockade, Shock, and Hyperkalemia (BRASH) Syndrome: A Case Report.
The BRASH syndrome is a recently recognized syndrome and the acronym stands for bradycardia, renal failure, atrioventricular (AV) blockade, shock, and hyperkalemia. We discuss a case of a 56-year-old female with a history of heart failure who presented in a critical state following recent adjustments to her carvedilol dosage while she was simultaneously on verapamil. This combination of AV nodal-blocking agents induced bradycardia in the patient, leading to shock and renal hypoperfusion complicated by hyperkalemia that required the use of a temporary transvenous pacemaker before she made a full recovery. The case report highlights the fact that this combination of medications alone may have had a synergistic effect that led to BRASH in our patient.


Teaching parents to conduct behavioral relaxation training with their hyperactive children.
Three boys meeting multiple criteria for hyperactivity received Behavioral Relaxation Training (BRT) in their homes from their parents, under the supervision of the experimenter. BRT involved modeling, prompting, token reinforcement, and praise, for ten overt relaxed behaviors. All children learned to relax to a criterion of at least 80% on the Behavioral Relaxation Scale (BRS), an objective measure of relaxation. Frontalis EMG levels were correlated with BRS scores for two children. Proficiency was maintained at one and three-month follow-ups. All children were removed from medication by follow-up. Parent ratings of hyperactive behavior on two standardized questionnaires showed improvements from baseline to follow-up. Teacher ratings of problem behavior were less consistently positive. The concept of relaxation as a skill rather than a state, and its implications as an alternative to medication therapy, are discussed.


Tolerance development in UChA and UChB rats by ethanol inhalation.
The development of tolerance by exposure to ethanol vapor in rats of the UChA and UChB strains has been studied. The exposure to ethanol vapor (6-7 mg per liter of air) during 46 hours developed clear tolerance to ethanol narcosis time in rats of both strains and sexes, while no tolerance to latency time was developed in any of these strains. Regarding the hypothermic effect of ethanol, only male rats of the UChB strains showed a decrease of rectal temperature significantly lower (p less than 0.05) than its respective control group. Blood alcohol levels (BALs) at awakening after the injection of ethanol (60 mmole/kg IP) were also determined. The results showed only a significantly lower BAL (p less than 0.05) in the females of the UChA strain subjected to ethanol inhalation.


Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial.
Herbal extracts from Commiphora mukul (guggul) have been widely used in Asia as cholesterol-lowering agents, and their popularity is increasing in the United States. Recently, guggulsterones, the purported bioactive compounds of guggul, have been shown to be potent antagonists of 2 nuclear hormone receptors involved in cholesterol metabolism, establishing a plausible mechanism of action for the hypolipidemic effects of these extracts. However, there are currently no published safety or efficacy data on the use of guggul extracts in Western populations. To study the short-term safety and efficacy of 2 doses of a standardized guggul extract (guggulipid, containing 2.5% guggulsterones) in healthy adults with hyperlipidemia eating a typical Western diet. Double-blind, randomized, placebo-controlled trial using a parallel design, conducted March 2000-August 2001. A total of 103 ambulatory, community-dwelling, healthy adults with hypercholesterolemia in the Philadelphia, Pa, metropolitan area. Oral, 3 times daily doses of standard-dose guggulipid (1000 mg), high-dose guggulipid (2000 mg), or matching placebo. Percentage change in levels of directly measured low-density lipoprotein cholesterol (LDL-C) after 8 weeks of therapy. Secondary outcome measures included levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, and directly measured very low-density lipoprotein cholesterol (VLDL-C), as well as adverse events reports and laboratory safety measures including electrolyte levels and hepatic and renal function. Compared with participants randomized to placebo (n = 36), in whom levels of LDL-C decreased by 5%, both standard-dose guggulipid (n = 33) and high-dose guggulipid (n = 34) raised levels of LDL-C by 4% (P =.01 vs placebo) and 5% (P =.006 vs placebo), respectively, at 8 weeks, for a net positive change of 9% to 10%. There were no significant changes in levels of total cholesterol, HDL-C, triglycerides, or VLDL-C in response to treatment with guggulipid in the intention-to-treat analysis. While guggulipid was generally well tolerated, 6 participants treated with guggulipid developed a hypersensitivity rash compared with none in the placebo group. Despite plausible mechanisms of action, guggulipid did not appear to improve levels of serum cholesterol over the short term in this population of adults with hypercholesterolemia, and might in fact raise levels of LDL-C. Guggulipid also appeared to cause a dermatologic hypersensitivity reaction in some patients.


The emotional well-being of parents with children at genetic risk for type 1 diabetes before and during participation in the POInT-study.
This study examined the emotional impact that parents experience when confronted with an increased genetic risk of type 1 diabetes (T1D) in their child. Population-based screening of neonates for genetic risk of chronic disease carries the risk of increased emotional burden for parents. Information was collected using a well-being questionnaire for parents of infants identified as having an increased risk for T1D in a multinational research study. Parents were asked to complete this questionnaire after they were told their child had an increased risk for T1D (Freder1k-study) and at several time points during an intervention study (POInT-study), where oral insulin was administered daily. Data were collected from 2595 parents of 1371 children across five countries. Panic-related anxiety symptoms were reported by only 4.9% after hearing about their child having an increased risk. Symptoms of depression were limited to 19.4% of the parents at the result-communication visit and declined over time during the intervention study. When thinking about their child's risk for developing T1D (disease-specific anxiety), 47.2% worried, felt nervous and tense. Mothers and parents with a first-degree relative (FDR) with T1D reported more symptoms of depression and disease-specific anxiety (p < 0.001) than fathers and parents without a FDR. Overall, symptoms of depression and panic-related anxiety are comparable with the German population. When asked about their child's risk for T1D during the intervention study, some parents reported disease-specific anxiety, which should be kept in mind when considering population-based screening. As certain subgroups are more prone, it will be important to continue psychological screening and, when necessary, to provide support by an experienced, multidisciplinary team.


Influence of various compounds on the degradation of hyaluronic acid by a myeloperoxidase system.
Myeloperoxidase in the presence of 0.7 mM hydrogen peroxide degrades hyaluronic by a mechanism which involves iron. Degradation is enhanced in the presence of chloride ion, which is attributed to the formation of hypochlorous acid. Myeloperoxidase-dependent degradation of hyaluronic acid is inhibited by superoxide dismutase, desferrioxamine, iodide ion, bromide ion, mannitol, histidine and various antiinflammatory agents. The destructing agent is presumably the hydroxyl radical.


Dipeptidyl peptidase-IV in chronic heart failure with reduced ejection fraction.
An association between dipeptidyl peptidase-IV (DPP-IV) inhibitors with worse prognosis in HF has been suggested. We aimed to assess the serum DPP-IV levels in chronic stable HF patients and determine their association with prognosis. Chronic stable HF patients with optimized prognostic-modifying therapy were prospectively recruited. 1) ejection fraction>50%, 2) hospitalizations or therapeutic adjustments in the previous 2months; 3) patients on renal replacement therapy, and 4) use of DPP-IV inhibitors. A fasting venous blood sample was collected and DPP-IV was measured. Patients were followed-up for 3years and the endpoint studied was all-cause death. Patients' characteristics were compared according to DPP-IV quartiles. A Cox regression analysis was performed and multivariate models were built. The 3rd DPP-IV quartile was the reference category. We studied 264 patients. Mean age: 69 (±13)years, 70.5% were male and 33.7% diabetic. Median (IQR) serum DPP-IV levels were 455.6 (350.0-625.5)ng/mL. DPP-IV had an inverse relationship with age. Patients in 3rd DPP-IV quartile were in lower NYHA classes and had the lowest 3years all-cause mortality. Patients in the 1st DPP-IV quartile had a multivariate adjusted HR of 3-year mortality of 2.62 (95%CI: 1.15-5.95) when compared with reference category and the HR for the 4th quartile was of 3.79 (95%CI: 1.68-8.54). There is a U-shaped association of serum DPP-IV with mortality in chronic systolic HF patients. Patients in the 3rd DPP-IV quartile have the best multivariate adjusted 3-year survival. DPP-IV inhibition might be harmful in patients with low DPP-IV.


Human CD8+ CTL recognition and in vitro lysis of herpes simplex virus-infected cells by a non-MHC restricted mechanism.
Cytotoxic T lymphocytes (CTL) are important for the recognition and lysis of virally infected cells, but their effectiveness can be limited by viral immune evasion mechanisms. We investigated the immunophenotype and function of human CD8+ T cells raised in response to herpes simplex virus (HSV). The expanded population contained cells of an activated and mature phenotype, as determined by the expressions of CD25, CD45RO, CD57, CD95 and HLA-DR. Cultured cells also expressed CD45RA. These cells lysed autologous and allogeneic HSV-infected lymphoblastoid cell line (LCL) targets via a non-major histocompatibility complex (MHC) restricted recognition pathway. Inhibition assays showed the mechanism of cytotoxicity to be calcium-dependent, granule exocytosis pathway, rather than the internal disintegration pathway. Cold target competition assays indicated that a common CTL population contributed to the recognition of autologous and allogeneic-infected targets. These effectors showed recognition of infected targets which was distinct from that of K562 cells. Non-MHC restricted lysis-associated molecule 2B4 (CD244) was upregulated on culturing and made a significant contribution to lysis of FcgammaR-bearing targets in a redirected killing assay. These findings suggest that CTL can recognize virally infected cells through a combination of non-MHC restricted mechanisms and may result in more efficient lysis than classical CD8+ T cells.


Bone status of senescent male rats: chemical, morphometric, and mechanical analysis.
The bone status of male rats 6, 12, and 24 months of age (n = 10) was examined. Femur calcium (Ca), phosphorus (P), and osteocalcin contents; serum chemistry; and mechanical properties of the bone were measured and correlated. Diaphyseal Ca, P, and osteocalcin contents were not different in animals 6 and 12 months of age but decreased significantly at 24 months: -7.4% for Ca, -4.2% for P, and -24% for osteocalcin compared to 12 months. Femurs from 24-month-old (senescent) rats were characterized by a scalloped appearance of the midfemoral endosteal surface and by cortical porosities. These age-associated changes coincided with nearly two-fold increases in serum immunoreactive parathyroid hormone (PTH) and osteocalcin. Serum Ca did not change with age, whereas serum P decreased (-14.8%) from 6 to 24 months. Maximum breaking force required to fracture femurs at midshaft did not change with age. Hence, the strength of the femur as an intact organ was not compromised with age despite the loss of diaphyseal Ca and P in the senescent animal. However, ultimate stress, a parameter that normalizes for differences in bone geometry and size, decreased 35% in femurs from 12- compared with 24-month-old animals. These mechanical results might be explained by the morphometric finding that, in contrast to the small but progressive age-associated increases in femur weight and length, the cortical and medullary areas increased at least two-fold. Therefore, the strength of the intact femur was maintained by architectural compensations, even though normalized tissue strength decreased with age. These findings suggest that bone status was compromised in the aged male rat.


Intraoperative performance and ultrastructural integrity of human capsulotomies created by the improved precision pulse capsulotomy device.
To investigate the intraoperative performance and the ultrastructural features of anterior capsulotomy performed with the improved Zepto precision pulse capsulotomy (PPC) device. Launceston Eye Institute, Launceston, Tasmania, Australia. Prospective, consecutive case series. Intraoperative observation of performance and complications were made on consecutive eyes having capsulotomies with the improved PPC device. The capsulotomy specimens were examined under scanning electron microscope and compared with manual continuous curvilinear capsulorhexis and femtosecond laser-assisted cataract surgery specimens. The study comprised 52 eyes. Intended capsulotomy occurred in 50 eyes with 2 device failures. Complete free-floating capsulotomies were achieved in 48 eyes (96%). Anterior capsule tears occurred in 2 eyes (4%). The ability of the PPC device to create complete free-floating capsulotomies improved; however, the radial tear rate remained high. The ultrastructural features in ex vivo human capsulotomy specimens still showed areas of irregular capsule margin with frayed edges.


Further Characterization of Hemopressin Peptide Fragments in the Opioid and Cannabinoid Systems.
Hemopressin, so-called because of its hypotensive effect, belongs to the derivatives of the hemoglobin α-chain. It was isolated from rat brain membrane homogenate by the use of catalytically inactive forms of endopeptidase 24.15 and neurolysin. Hemopressin has antihyperalgesic features that cannot be prevented by the opioid receptor antagonist, naloxone. In the present study, we investigated whether hemopressin (PVNFKFLSH) and its C-terminally truncated fragment hemopressin 1-7 (PVNFKFL) have any influence on opioid-dependent signaling. Peptides have been analyzed using G-protein-stimulating functional and receptor bindings in this experimental setup. These 2 compounds efficiently activated the G-proteins, and naloxone slightly blocked this stimulation. At the same time, they were able to displace radiolabeled [3H]DAMGO, a selective ligand for μ-opioid system, at micromolar concentrations. Displacement caused by the heptapeptide was more modest compared with hemopressin. Experiments performed on cell lines overexpressing μ-opioid receptors verified the opioid activity of both hemopressins. Moreover, the CB1 cannabinoid receptor antagonist, AM251, significantly decreased their G-protein stimulatory effect. Here, we further confirm that hemopressins can modulate CB1 receptors and can have a slight modulatory effect on the opioid system.


Effect of zolpidem on miniature IPSCs and occupancy of postsynaptic GABAA receptors in central synapses.
GABAA-mediated miniature IPSCs (mIPSCs) were recorded from layer V pyramidal neurons of the visual cortex using whole-cell patch-clamp recording in rat brain slices. At room temperature, the benzodiazepine site agonist zolpidem enhanced both the amplitude (to 138 +/- 26% of control value at 10 microM) and the duration (163 +/- 14%) of mIPSCs. The enhancement of mIPSC amplitude was not caused by an increase of the single-channel conductance of the postsynaptic receptors, as determined by peak-scaled non-stationary fluctuation analysis of mIPSCs. The effect of zolpidem on fast, synaptic-like (1 msec duration) applications of GABA to outside-out patches was also investigated. The EC50 for fast GABA applications was 310 microM. In patches, zolpidem enhanced the amplitude of currents elicited by subsaturating GABA applications (100-300 microM) but not by saturating applications (10 mM). The increase of mIPSC amplitude by zolpidem provides evidence that the GABAA receptors are not saturated during miniature synaptic transmission in the recorded cells. By comparing the facilitation induced by 1 microM zolpidem on outside-out patches and mIPSCs, we estimated the concentration of GABA seen by the postsynaptic GABAA receptors to be approximately 300 microM after single vesicle release. We have estimated a similar degree of receptor occupancy at room and physiological temperature. However, at 35 degreesC, zolpidem did not enhance the amplitude of mIPSCs or of subsaturating GABA applications on patches, implying that, in these neurons, zolpidem cannot be used to probe the degree of receptor occupancy at physiological temperature.


Results of cataract surgery in the very elderly population.
The aim of our study was to retrospectively evaluate the effectiveness and safety of cataract surgery and intraocular lens implantation (IOL) for patients aged 90 years or older, whom we define as "very elderly." The study involved a total number of 122 patients (122 eyes) with senile cataracts. The mean age of patients was 91.2 ± 2.3 years (range 90-100 years old). Phacoemulsification (phaco) was done on 113 of 122 eyes, and 9 of 122 eyes had extracapsular cataract extraction (ECCE). Postoperative visual acuity and intraocular pressure (IOP) were analyzed on the first postoperative day, 3 months after surgery, and 6 months after surgery. Best corrected visual acuity (BCVA) improved in 100 of 122 eyes (82.0%). BCVA remained the same in 20 of 122 eyes (16.4%) and decreased in 2 of 122 eyes (1.6%), mainly because of coexisting age-related macular degeneration (AMD). The BCVA 3 months after surgery was ≥0.8 in 23 of 122 eyes (18.9%), between 0.5 and 0.7 in 28 of 122 eyes (22.3%), and between 0.2 and 0.4 in 33 of 122 eyes (27.1%). We found significant implications of cataract surgery on decreasing IOP in the studied group of patients suffering from glaucoma compared to the patients without glaucoma. Advanced age is not a contraindication for cataract surgery. The results of the study showed that when systemic conditions are stable, both phaco and ECCE with IOL for very elderly patients are effective and safe.


A vascularised gracilis flap with tibial bone for the reconstruction of the Achilles tendon.
Rupture of the Achilles tendon is a very common trauma. Reconstruction of a chronic Achilles tendon defect is challenging for reconstructive surgeons, and several methods have been described. The ideal reconstruction would result in the patients resuming the activity level they were accustomed to before the injury. In our patient, the Achilles tendon was reconstructed using the gracilis muscle flap, and the flap was fixed using a fragment of the tibial bone, yielding satisfactory results. In this report, we describe this procedure employed and provide a description of the case.


Activation of neuropeptide Y Y1 receptors inhibits glutamate release through reduction of voltage-dependent Ca2+ entry in the rat cerebral cortex nerve terminals: suppression of this inhibitory effect by the protein kinase C-dependent facilitatory pathway.
Neuropeptide Y (NPY) is known to regulate the presynaptic glutamate release and neuronal responses to excitatory neurotransmission. The aim of this study was to investigate the effect of NPY on the release of endogenous glutamate from rat cerebrocortical nerve terminals (synaptosomes). NPY inhibited the Ca2+-dependent glutamate release evoked by 4-aminopyridine, and this inhibitory effect was mediated via NPY Y1 receptors, because it was mimicked by the specific NPY Y1 receptor agonist [Leu31 Pro34] NPY and blocked by the NPY Y1 receptor antagonist GR 231118. The inhibitory action of NPY was not due to it decreasing synaptosomal excitability or directly interfering with the release process at some point subsequent to Ca2+ influx, because NPY did not alter the 4-aminopyridine-evoked depolarization of the synaptosomal plasma membrane potential or ionomycin and hypertonic solution-induced glutamate release. Examination of the effect of NPY on the cytosolic [Ca2+] revealed that the inhibition of glutamate release could be attributed to a reduction in voltage-dependent Ca2+ influx. Consistent with this, the NPY-mediated inhibition of glutamate release was completely abolished in synaptosomes pretreated with N- and P/Q-type Ca2+ channel blocker, omega-conotoxin MVIIC. Moreover, NPY-mediated inhibition of 4-aminopyridine-evoked glutamate release was insensitive to KT 5720 and Ro32-0432 but was suppressed when protein kinase C was stimulated with phorbol ester. Together, these results suggest that NPY acting predominantly on NPY Y1 receptors inhibits glutamate release from rat cerebrocortical synaptosomes, likely by a mechanism involving direct coupling of receptors to N- and P/Q-type Ca2+ channels, and this coupling is subject to regulation by protein kinase C-dependent pathway. This implies that selective ligand for NPY receptors may be of value for treatment of conditions characterized by excessive glutamate release in the cerebral cortex.


Intensive care management of patients with viral encephalitis.
Viral encephalitis is a severe syndrome that can lead to encephalopathy, seizures, focal deficits, and neurological sequelae and death. It is mainly caused by neurotropic herpes viruses (i.e., HSV and VZV), although other pathogens may be observed in specific geographic regions or conditions. Recent advances in neuroimaging and molecular biology (PCR, metagenomics) allow for faster and more accurate etiological diagnoses, although their benefits need to be confirmed to provide guidelines for their use and interpretation. Despite intravenous acyclovir therapy and supportive care, outcomes remain poor in about two-thirds of herpes encephalitis patients requiring ICU admission. Randomized clinical trials focusing on symptomatic measures (i.e. early ICU admission, fever control, and treatment of seizures/status epilepticus) or adjunctive immunomodulatory therapies (i.e. steroids, intravenous immunoglobulins) to improve neurologic outcomes have not been conducted in the ICU setting. Large prospective multicenter studies combining clinical, electrophysiological, and neuroimaging data are needed to improve current knowledge on care pathways, long-term outcomes, and prognostication.


Glycine-like immunoreactivity in the cerebellum of rat and Senegalese baboon, Papio papio: a comparison with the distribution of GABA-like immunoreactivity and with [3H]glycine and [3H]GABA uptake.
An antiserum against conjugated glycine was characterized and applied to cerebellar sections of rats and baboons that had been perfusion-fixed with glutaraldehyde. After immunosorbent purification the serum reacted with brain protein-glutaraldehyde-glycine conjugates, but did not stain similar test conjugates prepared from other amino acids, including GABA and beta-alanine. In the rat cerebellum the glycine antiserum selectively labelled a subpopulation of Golgi neurons. Adjacent Vibratome sections treated with an antiserum against conjugated GABA revealed an about equally large subpopulation of immunopositive Golgi cells. A proportion of the Golgi cells that were cleaved by the plane of section contained both immunoreactivities. Additional evidence for a colocalization of glycine and GABA was obtained by postembedding staining of alternate semithin sections with the GABA antiserum and glycine antiserum, respectively. The ability of the antisera to distinguish between fixed glycine and GABA was corroborated by preincubation of the antisera with glutaraldehyde-amino acid fixation complexes: glycine complexes abolished staining with the glycine antiserum but had no effect on the GABA antiserum. The opposite effects were obtained with the GABA complexes. Matching the distributions of the respective immunoreactivities, [3H]glycine uptake was restricted to glomerulus-like structures in the granule cell layer whereas [3H]GABA uptake also occurred in punctate and fibrous profiles in the molecular layer. The baboon showed a distribution of glycine-like immunoreactivity similar to that in the rat, except that a few immunopositive neurons occurred in the molecular layer. The latter neurons were interpreted as outlying Golgi neurons; however, the possibility that they represent a subpopulation of basket cells could not be excluded. The Purkinje cells were negative in both species. Glial cells were weakly stained with the glycine antiserum but were strongly immunopositive after incubation with an antiserum raised against conjugates of the structurally similar amino acid beta-alanine. The present data suggest that glycine and GABA occur in about equally large subpopulations of Golgi neurons. A subpopulation of the Golgi neurons appears to contain both glycine and GABA.