TCTP overexpression reverses age-associated telomere attrition by upregulating telomerase activity in mouse oocytes.
A prolonged time span between ovulation and fertilization can cause postovulatory aging of oocytes, which impairs oocyte quality and subsequent embryo development. Telomere attrition has long been considered as the primary hallmark of aging or the cause of age-associated diseases. However, the status of telomere and its regulation during postovulatory oocyte aging are poorly understood. Here we found that oocytes experience telomere shortening during postovulatory aging, although they have the capacity to maintain telomere length. However, translationally controlled tumor protein (TCTP) overexpression could reverse age-associated telomere shortening by upregulating telomerase activity in mouse oocytes. Telomere length in mature oocytes gradually decreased with postovulatory aging, which was associated with a marked reduction in TRF1 expression, decreased telomerase activity, and decreased homologous combination (HR)-based alternative lengthening of telomeres (ALT) with a concomitant increase in oxidative stress. Surprisingly, however, overexpression of TCTP led to a remarkable increase in telomere length during postovulatory aging. Notably, neither TRF1 nor BRCA1 level was altered by TCTP overexpression. Moreover, TCTP-mediated telomere lengthening was not blocked by HR inhibition. In striking contrast, telomerase activity, as well as TERT and TERC levels, increased after TCTP overexpression. Importantly, unlike the chromosome-wide distribution of endogenous TCTP, overexpressed TCTP was ectopically localized at telomeres, implying that TCTP overexpression is required to increase telomerase activity. Collectively, our results demonstrate that TCTP prevents telomere attrition during postovulatory aging by upregulating telomerase activity in mouse oocytes.


Punking and bullying: strategies in middle school, high school, and beyond.
Punking is a practice of verbal and physical violence, humiliation, and shaming usually done in public by males to other males. This definition is based on interviews and discussion groups with 32 adolescent boys and on media sources within which adolescent males are embedded. Discourse analysis findings reveal that punking terminology and behaviors are usually interchangeable with bullying terminology and behaviors. Both practices are purposeful strategies taken up and used by many boys to affirm masculinity norms of toughness, strength, dominance, and control. Implications from this research promote a shift in understandings of how masculinity norms are achieved. Further, the research suggests that by bringing critical attention to social accountability for production of unhealthy norms and the violent practices that affirm these norms, we might well extend the scope and focus of intervention into harmful practices of violence, such as punking and bullying.


Recent development in antithrombotic therapy.
The present work reviews many newer concepts in antithrombotic therapy which have been introduced due to the understanding of the molecular thrombotic processes and to the advances in biotechnology and separation techniques.


Benefits and pitfalls in the merging of disciplines: the example of developmental psychopathology and the study of persons with autism.
Recent advances in the discipline of developmental psychopathology highlight the contributions of developmental thought to the study of persons with autism. This article briefly outlines primary developmental innovations in theory, methodology, and the interpretation of findings. Specifically. we discuss two sets of issues that arise from the general notion of developmental level. One set is relevant to the choice of persons that comprise the comparison group and the other to the various implications of the subjects' levels of functioning. In sum, we contend that researchers need to frame their empirical work within the context of developmental theory and methodology and interpret their findings accordingly. This will lead to scientifically compelling work and an increasingly heuristic approach to the study of persons with autism.


[Parisian psychiatric institutions under the Empire, as seen by a German visitor].
The author is setting out a book printed at Bayreuth in 1809 and stating a visit of parisian hospitals between 1806 and 1808 by the German botanist and medic August Friedrich Schweigger. The only part of that relation translated in French is concerning mental hospitals; it gives an out of ordinary look upon health cares in France during the 1st Empire.


Complications of laparoscopic cholecystectomy in Hungary: a multicentre study of 13,833 patients.
To report our countrywide experience of laparoscopic cholecystectomy with particular reference to complications. National multicentre retrospective study. 71 university departments and public hospitals in Hungary. 13,833 patients operated on between 1 January 1990 and 31 December 1993. Follow up by questionnaire. 732 patients (5.3%) required conversion to open cholecystectomy, urgently because of intraoperative complications in 204 (1.5%), electively for acute or chronic inflammation or obscure anatomy in 441 (3.2%), for unexpected findings in 72 (0.5%) and for technical problems in 15 (0.1%). There were postoperative complications in 598 (4.3%) but reoperation was indicated in only 154 patients (1.1%). There were bile duct injury in 81 (0.6%) and 199 bleeds (1.4%) which required conversion in 102 patients (0.7%) and reoperation in 38 (0.3%). 36 of the 181 postoperative recognized bile leaks required reoperation (20%). 19 patients died (0.1%). The morbidity and the mortality of laparoscopic cholecystectomy are better than after the open operation. The 2-6 times higher risk of bile duct injury mentioned in early studies was not confirmed.


Mutation of the Drosophila homologue of the Myb protooncogene causes genomic instability.
Vertebrates have three related Myb genes. The c-Myb protooncogene is required for definitive hematopoiesis in mice and when mutated causes leukemias and lymphomas in birds and mammals. The A-Myb gene is required for spermatogenesis and mammary gland proliferation in mice. The ubiquitously expressed B-Myb gene is essential for early embryonic development in mice and is directly regulated by the p16/cyclin D/Rb family/E2F pathway along with many critical S-phase genes. Drosophila has a single Myb gene most closely related to B-Myb. We have isolated two late-larval lethal alleles of Drosophila Myb. Mutant imaginal discs show an increased number of cells arrested in M phase. Mutant mitotic cells display a variety of abnormalities including spindle defects and increased polyploidy and aneuploidy. Remarkably, some mutant cells have an aberrant S- to M-phase transition in which replicating chromosomes undergo premature histone phosphorylation and chromosomal condensation. These results suggest that the absence of Drosophila Myb causes a defect in S phase that may result in M-phase abnormalities. Consistent with a role for Drosophila Myb during S phase, we detected Dm-Myb protein in S-phase nuclei of wild-type mitotic cells as well as endocycling cells, which lack both an M phase and cyclin B expression. Moreover, we found that the Dm-Myb protein is concentrated in regions of S-phase nuclei that are actively undergoing DNA replication. Together these findings imply that Dm-Myb provides an essential nontranscriptional function during chromosomal replication.


Kindred spirits? The benefits of egocentrism in close relationships.
The authors argue that people are happiest in their relationships when they believe they have found a kindred spirit, someone who understands them and shares their experiences. As reality may not always be that accommodating, however, intimates may find this sense of confidence by egocentrically assuming that their partners are mirrors of themselves. Both members of dating and married couples completed measures of satisfaction and felt understanding. They also described their own and their partners' traits, values, and day-to-day feelings. The results revealed that people in satisfying and stable relationships assimilated their partners to themselves, perceiving similarities that were not evident in reality. Such egocentrism predicted greater feelings of being understood, and feeling understood mediated the link between egocentrism and satisfaction in marriage.


The effect of contact area on friction measured with the portable inclinable articulated strut slip tester (PIAST).
A portable inclinable articulated strut slip tester (PIAST) measures friction at the shoe and floor interface. The squeeze-film effect with the PIAST is excessive in representing a human strike. The goal of this study was to investigate the effect of the contact area size on friction for reducing the squeeze-film effect. The footwear pad area of this slip meter was sequentially reduced from 7.62 cm square to 2.54 cm square. Five walkways were constructed. Friction was measured on each walkway under three surface conditions. Thirty-five participants rated their perceptions of slipperiness. The results indicated that the friction increased and plateaued as the size of the contact area was reduced. The effect of the pad size on the friction coefficient was statistically significant. The correlation coefficients between the friction and perception rating did not give a clear indication of what pad size might have a better correlation with human perception. Friction measurement at the shoe and floor interface is a critical issue in assessing potential interventions and identifying potentially dangerous locations for slip and fall incidents. This paper addresses a potential improvement in measuring friction on liquid-contaminated floor surfaces.


Optimization of Variance Reduction Techniques used in EGSnrc Monte Carlo Codes.
Monte Carlo (MC) simulations are often used in calculations of radiation transport to enable accurate prediction of radiation-dose, even though the computation is relatively time-consuming. In a typical MC simulation, significant computation time is allocated to following non-important events. To address this issue, variance reduction techniques (VRTs) have been suggested for reducing the statistical variance for the same computation time. Among the available MC simulation codes, electron gamma shower (National Research Council of Canada) (EGSnrc) is a general-purpose coupled electron-photon transport code that also features an even-handed, rich set of VRTs. The most well-known VRTs are the photon splitting, Russian roulette (RR), and photon cross-section enhancement (XCSE) techniques. The objective of this work was to determine the optimal combination of VRTs that increases the simulation speed and the efficiency of simulation, without compromising its accuracy. Selection of VRTs was performed using EGSnrc MC User codes, such as cavity and egs_chamber, for simulating various ion chamber geometries using 6 MV photon beams and 1.25 MeV 60Co photon beams. The results show that the combination of XCSE and RR yields the highest efficiency for ion-chamber dose calculations inside a 30 cm × 30 cm × 30 cm water phantom. Hence, properly selecting a different VRT without altering the underlying physics increases the efficiency of MC simulations for ion-chamber dose calculation.


Mouse embryonic stem cells maintain differentiation potency into somatic lineage despite alternation of ploidy.
Vertebrates, including mammals, are considered to have evolved by whole genome duplications. Although some fish have been reported to be polyploids that have undergone additional genome duplication, there have been no reports of polyploid mammals due to abnormal development after implantation. Furthermore, as the number of physiologically existing tetraploid somatic cells is small, details of the functions of these ploidy-altered cells are not fully understood. In this present study, we aimed to clarify the details of the differentiation potency of tetraploids using tetraploid embryonic stem cells. To clarify the differentiation potency, we used mouse tetraploid embryonic stem cells derived from tetraploid embryos. We presented tetraploid embryonic stem cells differentiated into neural and osteocyte lineage in vitro and tetraploid cells that contributed to various tissues of chimeric embryos ubiquitously in vivo. These results revealed that mouse embryonic stem cells maintain differentiation potency after altering the ploidy. Our results provide an important basis for the differentiation dynamics of germ layers in mammalian polyploid embryogenesis.


The evaluation of physical exam findings in patients assessed for suspected burn inhalation injury.
The purpose of this investigation was to evaluate the utility of singed nasal hair (SN), carbonaceous sputum (CS), and facial burns (FB) as indicators of burn inhalation injury, when compared to the accepted standard of bronchoscopic diagnosis of inhalation injury. An institutional review board approved, retrospective review was conducted. All patients were suspected to have burn inhalation injury and subsequently underwent bronchoscopic evaluation. Data collected included: percent burn TBSA, burn injury mechanism, admission physical exam findings (SN, CS, FB), and bronchoscopy findings. Thirty-five males and twelve females met inclusion criteria (n = 47). Bronchoscopy was normal in 31 patients (66%). Data were analyzed as all patients and in subgroups according to burn TBSA and an enclosed space mechanism of injury. Physical exam findings (SN, CS, FB) were evaluated individually and in combination. Overall, the sensitivities, specificities, positive predictive values, and negative predictive values calculated were poor and inconsistent, and they did not improve within subgroup analysis or when physical findings were combined. Further statistical analysis suggested the physical findings, whether in isolation or in combination, have poor discrimination between patients that have and do not have inhalation injury (AUC < 0.7, P > .05) and poor agreement with the diagnosis made by bronchoscopy (κ < 0.4, P > .05). This remained true in the subgroup analysis as well. Our data demonstrated the findings of SN, CS, and FB are unreliable evidence for inhalation injury, even in the context of an enclosed space mechanism of injury. Thus, these physical findings are not absolute indicators for intubation and should be interpreted as one component of the history and physical.


Viral gene expression in HIV transgenic mice is activated by Mycobacterium tuberculosis and suppressed after antimycobacterial chemotherapy.
We used human immunodeficiency virus (HIV) transgenic (Tg) mice incorporating the entire viral genome to study the effect of Mycobacterium tuberculosis infection on the induction of integrated HIV gene expression. When aerogenically infected with M. tuberculosis, these mice displayed a progressive increase in pulmonary gag and env mRNA levels and of p24 antigen production by cultured splenocytes. In situ hybridization of lungs revealed increased viral transcription associated with areas of inflammation and acid-fast bacilli. By neutralizing tumor necrosis factor (TNF) in vivo after M. tuberculosis exposure, we found that, although initially TNF independent, the increased HIV expression triggered by M. tuberculosis was highly dependent on this cytokine by 4 weeks after infection. Furthermore, treatment with antimycobacterial drugs markedly reduced HIV transgene expression. These studies establish an animal model for investigating the influence of M. tuberculosis on latent HIV expression and for testing therapeutic regimens for reducing the disease burden in patients with acquired immunodeficiency syndrome-associated tuberculosis.


Burning mouth syndrome.
Objective To review the clinical entity of primary burning mouth syndrome (BMS), its pathophysiological mechanisms, accurate new diagnostic methods and evidence-based treatment options, and to describe novel lines for future research regarding aetiology, pathophysiology, and new therapeutic strategies. Description Primary BMS is a chronic neuropathic intraoral pain condition that despite typical symptoms lacks clear clinical signs of neuropathic involvement. With advanced diagnostic methods, such as quantitative sensory testing of small somatosensory and taste afferents, neurophysiological recordings of the trigeminal system, and peripheral nerve blocks, most BMS patients can be classified into the peripheral or central type of neuropathic pain. These two types differ regarding pathophysiological mechanisms, efficacy of available treatments, and psychiatric comorbidity. The two types may overlap in individual patients. BMS is most frequent in postmenopausal women, with general population prevalence of around 1%. Treatment of BMS is difficult; best evidence exists for efficacy of topical and systemic clonazepam. Hormonal substitution, dopaminergic medications, and therapeutic non-invasive neuromodulation may provide efficient mechanism-based treatments for BMS in the future. Conclusion We present a novel comprehensive hypothesis of primary BMS, gathering the hormonal, neuropathic, and genetic factors presumably required in the genesis of the condition. This will aid in future research on pathophysiology and risk factors of BMS, and boost treatment trials taking into account individual mechanism profiles and subgroup-clusters.


Does case management work? The evidence and the abuse of evidence-based medicine.
This study reviews typologies of psychiatric case management and then discusses the efficacy, effectiveness and cost effectiveness of psychiatric case management, with particular focus on evidence from Australia and the UK. Subsequently, it aims to examine the way such evidence has been interpreted in the context of UK psychiatric research and services. Finally it examines the ways in which, by the selective reviewing or editorializing of evidence, case management has been brought into disrepute in the UK. This study reviews literature of the recent evidence for case management, and asks three questions of case management: has it been shown to be efficacious in controlled research, is it effective in applied settings, and is it cost effective? An examination is then made of the concurrent representations of the UK evidence in both the academic literature and the media. There is strong evidence for the efficacy effectiveness and cost-effectiveness of case management in psychiatry, the closer it conforms to active and assertive community treatment models. It appears, however, that studies and evidence-based reviews of case management have possibly been misused and misrepresented in a highly charged atmosphere of professional media debate. The potential for this abuse is not limited to psychiatry and remains a challenge for all evidence-based practice. On the evidence, assertive community treatment case management is one of the most effective interventions in psychiatry today. Despite improving the evidence base for practice (e.g. as has occurred for case-management in psychiatry), evidence-based medicine (EBM) is still susceptible to compromise and misrepresentation, due to unexamined or undeclared bias. Unless this potential for abuse is recognized and checked, EBM in psychiatry is in danger of being discredited at the hand of some of its own proponents. There is a need for more rigorous pursuit of evidence-based psychiatry, including more systematic declaration of bias in all research, whether quantitative or qualitative in design.


Priming guesses on a forced-recall test.
The forced-recall paradigm requires participants to fill all spaces on the memory test even if they cannot remember all the list words. In the present study, the authors used that paradigm to examine the influence of implicit memory on guessing--when participants fill remaining spaces after they cannot remember list items. They measured explicit memory as the percentage of targets that participants designated as remembered from the list and implicit memory as the percentage of targets they wrote but did not designate as remembered (beyond chance level). The authors examined implicit memory on guessing with forced recall (Experiment 1), forced cued recall with younger and older adults (Experiment 2), and forced free and cued recall under a depth-of-processing manipulation (Experiment 3). They conclude that implicit memory influences guesses of targets in the forced-recall paradigm.


Piezosurgery: a new method for osteotomies in rhinoplasty.
Two basic techniques for lateral osteotomy have been developed to date; the internal (endonasal) continuous technique and the external (percutaneous) perforating method. Numerous investigators have subjectively reported that the application of the two techniques results in less postoperative ecchymosis and edema compared to the use of other techniques, but an alternative and gentle method for performing lateral osteotomy or bony hump removal has not been proposed yet. The authors present a new soft technique to perform nasal osteotomy in rhinoplasty using piezoelectric ultrasonic vibrations, and emphasize the advantages of this method.


IPASS: a study on the tolerability and effectiveness of injectable testosterone undecanoate for the treatment of male hypogonadism in a worldwide sample of 1,438 men.
Morbidity/mortality is higher in men with below-normal serum testosterone. Restoring testosterone to normal is beneficial. Assessment of safety and effectiveness of injectable long-acting testosterone undecanoate (TU) in hypogonadal men in daily clinical practice. An international, multicenter, one-arm, prospective observational study in 23 countries. Parameters of erectile function, libido, vigor/vitality, mood, and ability to concentrate assessed by physician interview using items and five-point Likert scales. Physical and circulatory parameters as well as hematocrit, prostate-specific antigen (PSA) levels, glucose control, and lipid profiles. IPASS: An International, multicenter, Post-Authorisation (after authorized use in respective country) Surveillance Study on long-acting-intramuscular TU conducted at 155 centers in 23 countries in Europe, Asia, Latin America, and Australia. Patients received up to five TU injections during 9-12 months. Of the 1,493 hypogonadal men enrolled, 1,438 (aged 49.2 ± 13.9 years) having received 6,333 injections were analyzed. Scores of mental and psychosexual functions (libido, vigor, overall mood, and ability to concentrate) improved markedly, while mean waist circumference decreased from 100 to 96 cm. Blood pressure and lipid parameters were altered in a favorable and significant manner. After four TU injection intervals, the percentage of patients with "low" or "very low" levels of sexual desire/libido decreased from 64% at baseline to 10%; moderate, severe, or extremely severe erectile dysfunction decreased from 67% to 19%. At the last observation, 89% of patients were "satisfied" or "very satisfied" with TU therapy. Adverse events and adverse drug reactions (ADRs) occurred in 12% and 6% of patients, respectively, mostly mild to moderate. The most common ADRs were increase in hematocrit, increase in PSA, and injection site pain (all <1%). No case of prostate cancer was observed. In this largest worldwide sample of hypogonadal men, injectable long-acting TU was effective and well tolerated.


Phosphorylation and dephosphorylation of human myristoyltransferase type 1.
N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the co-translational and (or) post-translational transfer of myristate to the amino terminal glycine residue of a number of important proteins, especially the non-receptor tyrosine kinases whose activity is important for tumorigenesis. Human NMT was found to be phosphorylated by non-receptor tyrosine kinase family members of Lyn, Fyn, and Lck and dephosphorylated by the Ca2+/calmodulin-dependent protein phosphatase, calcineurin. In this review, we discuss the cross-talk that exists between NMT and their N-myristoylated protein substrates. The cross-talk among NMT, tyrosine kinases, and phosphatases may be determined by their subcellular localization and by the physiological state of the cell.


Most Helicobacter pylori-infected patients have specific antibodies, and some also have H. pylori antigens and genomic material in bile: is it a risk factor for gallstone formation?
Bile may contain a 130-kDa protein endowed with aminopeptidase activity and the ability to promote cholesterol crystallisation. As >90% of H. pylori strains have a similar peptidase activity, and half the isolates express a 110- to 140-kDa antigen, the CagA protein, we investigated a possible association between H. pylori infection and gallstones, and the presence in bile samples of factors related to H. pylori that could increase cholesterol crystallization. The prevalence of H. pylori infection was 82.1% in 112 patients with gallstones and 80.3% in 112 controls (NS). Fifteen bile samples out of 23 specimens from infected patients (65.2%) contained anti-CagA antibodies. A approximately 60-kDa antigen only reacting with an anti-CagA antibody was found in five bile samples (21.7%) from 23 infected patients. One bile sample (4.1%) contained ureA and cagA genes of H. pylori. The homology of CagA with the N-terminal sequence of aminopeptidase N was very low. We concluded that the presence of specific antibody to H. pylori in most bile samples tested and of an H. pylori putative antigen in a discrete number of cases may represent factors that increase the risk of gallstone formation.


The use of a single-fiber reactor for the enzymatic removal of amino acids from solutions.
In this article we describe the use of bench-scale single-fiber dialyzers for the development and testing of an immobilized enzyme reactor for the treatment of leukemia. The treatment is based on the enzymatic removal of specific amino acids from the blood of leukemia patients. L-Lysine alpha-oxidase and catalase were coimmobilized within the void space of the porous region of asymmetric hollow-fiber membranes for the removal of L-lysine from simulated human plasma solutions. Hollow-fiber reactor performance was evaluated using a small single-fiber dialyzer (SFD) consisting of a single fiber encased in a protective glass shell. This small reactor affords ease of use, requires small amounts of chemicals and biochemicals, and gives useful reactor performance data. Single-fiber dialyzers were constructed using polyamide fibers with a molecular weight cutoff of 10,000 (PA10 fibers); these fibers demonstrated the best compatibility with and retention of the enzymes. The SFD performance in removing L-lysine from solution was evaluated under both steady and pulsatile flow operation. Pulsatile flow was tested for two reasons: (1) to enhance the radial mass transfer of lysine within the SFD and (2) to simulate the pulsatile flow of blood in dialysis treatment. The use of pulsatile flow increased lysine conversion by 15% over the steady-flow case. Approximately 40% of the lysine was removed from simulated plasma by the SFD in a 4-h experiment using pulsatile flow in the recycle mode.


Recent progress in synchrotron-based frequency-domain Fourier-transform THz-EPR.
We describe frequency-domain Fourier-transform THz-EPR as a method to assign spin-coupling parameters of high-spin (S>1/2) systems with very large zero-field splittings. The instrumental foundations of synchrotron-based FD-FT THz-EPR are presented, alongside with a discussion of frequency-domain EPR simulation routines. The capabilities of this approach is demonstrated for selected mono- and multinuclear HS systems. Finally, we discuss remaining challenges and give an outlook on the future prospects of the technique.


Influence of Different Modalities of Grape Withering on Volatile Compounds of Young and Aged Corvina Wines.
Withering is a practice traditionally used in various regions to produce sweet or dry wines. During withering there is an increase in sugar content but also a modification in volatile compound profiles. Controlling metabolic changes through the dehydration process to obtain wines with desired characteristics is therefore a challenging opportunity. The effects of two different withering technologies, post-harvest or on-vine with blocked sap vessel flow, on the volatile profile of young and aged Corvina red wines was investigated. The results showed that modulation of wine aroma due to the withering process is associated with fermentative metabolites, such as esters, higher alcohols, and acids, as well as grape-related compounds such as C6 alcohols, terpenes and norisoprenoids. Significant differences were also found by comparing the two withering techniques. Post-harvest in a traditional "fruttaio" warehouse wines showed higher content of ethyl acetate, ethyl butanoate, β-citronellol and 3-oxo-α-ionol, whereas post-harvest withering on-vine increased β-damascenone in wines. The type of withering technique has an influence on the evolution of some aroma compounds during the aging of wine, among them linalool, (E)-1-(2,3,6-trimethylphenyl)buta-1,3-diene (TPB), n-hexyl acetate, ethyl acetate, ethyl 3-methylbutanoate, 3-oxo-α-ionol and β-damascenone.


Progressive leukoencephalopathy caused by primary CNS lymphoma.
Prominent leukoaraiosis is common in the clinical routine setting. In addition to microatheroma and hypertensive small vessel disease (lipohyalinosis), a large number of rare but clinically relevant differential diagnoses have to be considered. A man in his 60s presented with left pontine infarction and subsequent rapidly deteriorating leukoaraiosis associated with dementia. Standard non-invasive examination did not enable the correct diagnosis to be obtained. A brain biopsy sample revealed a combination of diffuse infiltrating and intravascular large B cell central nervous system (CNS) lymphoma, which has not previously been described in literature. Despite immediate treatment with state of the art chemotherapy, the patient died 3 months after the onset of symptoms. Diffuse infiltrating and intravascular primary CNS lymphoma is a rare cause of rapidly progressive leukoencephalopathy and stroke mediated by neoplastic microvessel occlusion and inflammatory tissue damage. This report intends to increase awareness among neurologists and other stroke physicians about this disease in order to accelerate diagnosis and initiation of treatment.


miR-27-3p inhibition restore fibroblasts viability in diabetic wound by targeting NOVA1.
Diabetic wounds increase morbidity and decrease quality of life in patients with type 2 diabetes. Serum miR-27-3p levels are reportedly elevated in type 2 diabetic patients. In the present study, we explored the role of miR-27-3p during wound healing. We found that miR-27-3p is overexpressed in cutaneous fibroblasts of diabetic patients and mice. miR-27-3p knockdown enhanced the proliferation and migration of fibroblasts, while suppressing the incidence of fibroblast apoptosis. Overexpressing miR-27-3p in fibroblasts had the opposite effects. We also identified neuro-oncological ventral antigen 1 (NOVA1) as a target of miR-27-3p in fibroblasts. Knocking down NOVA1 using targeted siRNA mimicked the effects of miR-27-3p overexpression in fibroblasts. Administration of miR-27-3p to the area around wounds inflicted in mice delayed healing of those wounds. This suggests that miR-27-3p suppresses fibroblast function by targeting NOVA1, which results in the slowing of wound healing. These findings may offer a new approach to the treatment of diabetic wound healing.


Rubber band ligation for 750 cases of symptomatic hemorrhoids out of 2200 cases.
To study the results for the treatment of symptomatic hemorrhoids using rubber band ligation (RBL) method. A retrospective study for 750 patients who came to the colorectal unit from June, 1998 to September, 2006, data was retrieved from archived files. RBL was performed using the Mc Gown applicator on an outpatient basis. The patients were asked to return to out-patient clinic for follow up at 2 wk, 1 mo, 6 mo and through telephone call every 6 mo for 2 years). After RBL, 696 patients (92.8%) were cured with no difference in outcome for second or third degree hemorrhoids (P = 0.31). Symptomatic recurrence was detected in 11.04% after 2 years. A total of 52 patients (6.93%) had 77 complications from RBL which required no hospitalization. Complications were pain, rectal bleeding and vaso-vagal symptoms (4.13%, 4.13% and 1.33% of patients, respectively). At 1 mo there were a significant improvement in mean SF-36 scores over baseline in five items, while after 2 years there were improvement in all items over baseline, but not significant. No significant manometeric changes after band ligation. RBL is a simple, safe and effective method for treating symptomatic second and third degree hemorrhoids as an out patient procedure with significant improvement in quality of life. RBL doesn't alter ano-rectal functions.


The efficacy of antimalarials in systemic lupus erythematosus.
Of 209 patients who fulfilled the A.R.A. criteria for the diagnosis of systemic lupus erythematosus, 43 were selected for study because each had been treated for at least two years with antimalarials, but had not received antimalarials for at least one subsequent year. In each instance, the antimalarial was discontinued solely because of the development of retinopathy. Each year on antimalarials was matched with a subsequent year off antimalarials for each patient. The year immediately following diagnosis and years of pregnancy were excluded. Paired-t test analysis of matched years revealed that general symptoms (fever, fatigue, weight loss) were less common during years on 500 mg chloroquine daily than during years off the drug (p less than 0.05). Skin manifestations were also less frequent during the years on 500 mg chloroquine daily than during the years off (p less than 0.05). No significant steroid sparing effect was found. However, a greater incidence of flare-ups during the matched years off the drug was statistically significant.


Novel approaches to treatment of leptomeningeal metastases.
The incidence of leptomeningeal metastases is increasing in the setting of improved survival from systemic cancers. In more recent years, our understanding of leptomeningeal metastasis pathogenesis, how to diagnose and treat has been evolving. Diagnosing leptomeningeal metastasis has been challenging due to the limitations of cytology and neuroimaging; However, newer techniques detecting circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) have shown potential advantage with diagnosis, quantification and detection of oncogenic mutations. The use of small molecule inhibitors and immunotherapy has shown some promise in specific leptomeningeal metastasis subtypes. These new discoveries have improved clinical trials' ability to assess treatment response and thereby more optimally compare different treatments. Furthermore, they have helped the individual clinician better diagnose, monitor the disease and provide novel therapies.


Department of Defense Medical Examination Review Board Audiogram Screening Comparative Analysis.
The Department of Defense Medical Examination Review Board (DoDMERB) plays a pivotal role in the assessment of medical fitness for aspiring military officers. A crucial component of this process is the screening audiogram, designed to evaluate hearing capabilities. However, recent observations of high disqualification rates following screening audiograms led to concerns about their accuracy. This quality improvement project, conducted between 2017 and 2019, aimed to assess the concordance between screening audiograms and reference-standard audiometry, as well as to investigate the relationship between disqualification status and hearing thresholds at different frequencies. A sample of 134 candidates, drawn from various locations across the United States, was analyzed. Results revealed that the screening audiogram mean thresholds were twice that of the reference-standard audiogram, particularly in the lower frequencies. Additionally, we found that 84% of candidates were incorrectly disqualified by the screening exam when followed up by the reference-standard. Overall, Bland-Altman analysis revealed significant disagreement between these two tests. This discrepancy prompted a fundamental policy shift in 2020, where candidates who fail screening audiograms now automatically undergo reference-standard audiometry before any disqualification decision. This policy change reflects the commitment of DoDMERB to refining the medical screening process. It reduces the burden on candidates, provides a more comprehensive assessment, and ensures that qualified individuals are not erroneously disqualified.In addition to policy changes, this quality improvement project explored potential courses of action to enhance the screening audiogram process. Among these, improving contract specifications for testing facilities to minimize ambient noise emerged as the most practical and cost-effective approach. In conclusion, the project underscores the importance of refining medical screening processes to accurately assess candidates' qualifications while retaining the utility of screening audiograms. These efforts not only benefit aspiring military officers but also contribute to maintaining the high standards required for military service.


Successful Thrombolysis despite Having an Incidental Unruptured Cerebral Aneurysm.
Purpose. To report a case of successful thrombolysis performed in a patient with an incidental unruptured intracranial aneurysm and review the literature. Case Report. Patient admitted for ischemic stroke due to left posterior cerebral artery occlusion, with an incidental right middle cerebral artery aneurysm, who underwent treatment with tissue plasminogen activator (rtPA) resulting in clinical improvement without complications. Conclusion. The presence of unruptured intracranial aneurysms is considered as a contraindication to thrombolysis, due to a potentially higher hemorrhagic risk of aneurysm rupture. Patients, otherwise, eligible for thrombolysis are usually excluded from receiving this emergent treatment, despite its potential benefits. A reevaluation of the strict exclusion criteria for thrombolysis in acute stroke patients should be considered.


Antibodies in crevicular fluid: an epidemiological tool for investigation of waterborne disease.
A significant challenge in the epidemiological investigation of recreational waterborne disease is the establishment of a definite association between exposure to a contaminated water and infection. An increase in specific antibodies as a result of infection is a potent measure of disease exposure and its determination would enhance epidemiological studies of waterborne diseases. We report on the automated detection of HAV antibodies in crevicular fluid and its use in a field study. The method is easy to use, non-invasive, could be applied to volunteers of all ages and is comparable in sensitivity to serological procedures. Application to an epidemiological study of water recreationalists demonstrated that surfers were three times more likely to be immune to hepatitis A virus than either wind-surfers or a control group without recreational water contact.


Bioengineering of Metal-organic Frameworks for Nanomedicine.
Controlled structure, tunable porosity, and readily chemical functionalizability make metal-organic frameworks (MOFs) a powerful biomedical tool. Nanoscale MOF particles have been increasingly studied as drug carriers, bioimaging agents, and therapeutic agents due to their excellent physiochemical properties. In this review, we start with MOF as a nanocarrier for drug delivery, covering therapeutic MOF agents followed by a comprehensive discussion of surface bioengineering of MOF for improved biostability, biocompatibility, and targeted delivery. Finally, we detail the challenges and prospects of the future of MOF research for biomedical applications.


The impact of anion ordering on octahedra distortion and phase transitions in SrTaO2N and BaTaO2N.
In this work we synthesized BaTaO2N and SrTaO2N using a two-step high-temperature solid-state reaction method and analysed the structural distortions, relative to the ideal cubic perovskite structure, according to group theory. From a complete distortion analysis/refinement using high-resolution neutron diffraction data in the temperature range 8 to 613 K, we identified tetragonal structures for BaTaO2N [P4/mmm (No. 123)] and SrTaO2N [I4/mcm (No. 140)]. In contrast to an anion-disordered cubic perovskite (Pm \overline{3}m No. 221) with Ta at the cell center, both systems show a site preference for oxygen anions in the two opposite corners (along the c axis) of the Ta-O/N octahedra rather than the four square corners in the ab plane (Γ3+ occupancy distortion), which induces a tetragonal elongation of the unit cell with the c axis being longer than the a axis. A further Ta-O/N octahedra displacement [R5-(a,0,0), rotation about the c axis] distortion was observed in SrTaO2N. This distortion mode is accompanied by an increased unit-cell distortion that decreases as the temperature increases. Ultimately a second-order phase transition caused by the loss of the R5-(a,0,0) mode was observed at 400-450 K.


[Fixed drug eruption induced by sulfaguanidine].
Fixed drug eruption is a lesion induced by drugs. The family of drugs usually incriminated are sulfonamides, tetracyclines and pyrazols. We describe nine cases of fixed drug eruption induced by sulfaguanidine, a sulfonamide with local action. All the patients presented one or more fixed drug eruption reactivation lesions induced by sulfaguanidine as self-medication for diarrhea. The number of lesions increased in 7 cases after reactivation. The delay in occurrence of the fixed drug eruption decreased during the different episodes. The lesions predominated on the hands in 8 cases of 9. The sulfaguanidine must be added to the list of drug-induced fixed drug eruptions with limited absorption from the gastrointestinal tract.


Recent studies on antibiotics and small molecular immunomodulators with potential usefulness in treating lung cancer: Part I - Antitumor antibiotics and their derivatives.
Aclacinomycin, isolated from the culture of a Streptomyces, and 4'-O-tetrahydropyranyladriamycin, prepared by chemical derivation, exhibit significantly low cardiac toxicity and more effectiveness than does adriamycin. Pepleomycin, a new derivative of bleomycin, has 4-5 times lower pulmonary toxicity and more potent activity than the parent antibiotic. The future prospects of studies on antibiotics with potential usefulness in treatment of lung cancer are discussed.


Surgical treatment of spinal cavernous angiomas.
Cavernous angiomas are vascular malformations that can occur in several compartments of the spine. Depending on their location, these lesions present particular clinico-diagnostic findings, and may require different modalities of treatment. The authors report a series of 10 patients with vertebral, epidural, subdural extra- and intramedullary cavernous angiomas. Clinical and radiological features, as well as surgical results of this series are presented. The different modalities of surgical treatment of cavernous angiomas variously placed along the spine are discussed.


The effect of angulation sensors on implant placement.
It is hypothesized that use of an angulation sensor could increase the alignment accuracy of multiple implant osteotomies without requiring the use of guided-surgical templates. Therefore, the purpose of this study was to determine if use of such a sensor mounted on a surgical handpiece could improve implant placement.


A review of the value of quadrivalent influenza vaccines and their potential contribution to influenza control.
The contribution of influenza B to the seasonal influenza burden varies from year-to-year. Although 2 antigenically distinct influenza B virus lineages have co-circulated since 2001, trivalent influenza vaccines (TIVs) contain antigens from only one influenza B virus. B-mismatch or co-circulation of both B lineages results in increased morbidity and mortality attributable to the B lineage absent from the vaccine. Quadrivalent vaccines (QIVs) contain both influenza B lineages. We reviewed currently licensed QIVs and their value by focusing on the preventable disease burden. Modeling studies support that QIVs are expected to prevent more influenza cases, hospitalisations and deaths than TIVs, although estimates of the case numbers prevented vary according to local specificities. The value of QIVs is demonstrated by their capacity to broaden the immune response and reduce the likelihood of a B-mismatched season. Some health authorities have preferentially recommended QIVs over TIVs in their influenza prevention programmes.


A description of Mycobacterium chelonae subsp. gwanakae subsp. nov., a rapidly growing mycobacterium with a smooth colony phenotype due to glycopeptidolipids.
Three rapidly growing mycobacterial strains, MOTTH4W, MOTT36WT and MOTT68W, were isolated from the sputa of three independent Korean patients co-infected with Mycobacterium yongonense Type II strains. The 16S rRNA gene sequences of all three strains were unique, which were closest to that of Mycobacterium chelonae subsp. bovis KCTC 39630T (99.9 % similarity). Multilocus sequence typing analysis targeting 10 housekeeping genes including hsp65 and rpoB revealed the distinct phylogenetic location of these strains, which were clustered with M. chelonae subsp. chelonae ATCC 35752T and M. chelonae subsp. bovis KCTC 39630T. Phylogenetic analysis based on whole genome sequences revealed a 95.89 % average nucleotide identity (ANI) value with M. chelonae subsp. chelonae, slightly higher than the 95.0 % ANI criterion for determining a novel species. In addition, phenotypic characteristics such as a smooth colony morphology and growth inhibition at 37 °C, distinct MALDI-TOF MS profiles of extracted total lipids due to surface glycopeptidolipids, and distinct drug susceptibility profiles further supported the taxonomic characterization of these strains as representing a novel subspecies of Mycobacterium chelonae. Mycobacterium chelonae subsp. gwanakae subsp. nov. is proposed and the type strain is MOTT36WT (=KCTC 29127T=JCM 32454T).


Antibacterial and Antifungal Activities of Lectin Extracted from Fruiting Bodies of the Korean Cauliflower Medicinal Mushroom, Sparassis latifolia (Agaricomycetes).
In this article we describe the isolation and characterization of a novel lectin from fruiting bodies of the mushroom Sparassis latifolia. The antibacterial activity of the purified lectin against Escherichia coli and resistant strains of Staphylococcus aureus and Pseudomonas aeruginosa as well as the antifungal activity against Candida and Fusarium species were determined. Circular dichroism spectroscopy and the tryptophan blue shift assay indicated that the lectin interacts with microbial surfaces. This suggests the potential of the lectin isolated from S. latifolia, a valuable source of bioactive constituents, as a therapeutic in pharmaceutical agent.


Deficits in Approximate Number System Acuity and Mathematical Abilities in 6.5-Year-Old Children Born Extremely Preterm.
Preterm children are at increased risk for poor academic achievement, especially in math. In the present study, we examined whether preterm children differ from term-born children in their intuitive sense of number that relies on an unlearned, approximate number system (ANS) and whether there is a link between preterm children's ANS acuity and their math abilities. To this end, 6.5-year-old extremely preterm (i.e., <27 weeks gestation, n = 82) and term-born children (n = 89) completed a non-symbolic number comparison (ANS acuity) task and a standardized math test. We found that extremely preterm children had significantly lower ANS acuity than term-born children and that these differences could not be fully explained by differences in verbal IQ, perceptual reasoning skills, working memory, or attention. Differences in ANS acuity persisted even when demands on visuo-spatial skills and attention were reduced in the ANS task. Finally, we found that ANS acuity and math ability are linked in extremely preterm children, similar to previous results from term-born children. These results suggest that deficits in the ANS may be at least partly responsible for the deficits in math abilities often observed in extremely preterm children.


Hip abductor neuromuscular capacity: A limiting factor in mediolateral balance control in older adults?
Mediolateral balance impairment is an important cause of falling in older adults. We aimed to investigate whether hip abductor muscular strength and/or position sense are limiting factors in mediolateral balance control. Sixteen community-dwelling older adults performed three different mediolateral weight-shifting tasks, by tracking (1) a sinusoidally moving visual target, "visual-MELBA"; (2) a sinusoidally translating platform without explicit visual feedback, "mechanical-MELBA"; and (3) an unpredictable platform translation, "sudden-platform-translation." Balance performance was quantified for each task and correlated with hip abductor position sense, isometric strength, and peak hip abduction/adduction moments and moment rates. Participants with better balance performance showed higher and faster hip abduction/adduction moment production during the tasks. Isometric hip abductor strength was significantly correlated with accuracy of tracking the visual target, while hip abductor position sense was associated with the bandwidth over which the mechanical target could be tracked and with a smaller delay between CoM movement and the sudden-platform movement. Hip abductor muscles play an important role in mediolateral balance control. Accurate balance performance appears limited by lower hip abductor strength when explicit visual information on balance reduces the need for hip abductor proprioception, while proprioceptive acuity may limit balance performance when no explicit enhanced feedback is presented and required weight shifts have to be inferred from "normal" sensory information.


A survey of tick-borne bacteria and protozoa in naturally exposed dogs from Israel.
Antibody reactivity against seven bacterial or protozoal pathogens was measured in sera derived from 40 dogs suspected of a tick-borne disease. Sera from 73% (29/40) of the dogs reacted with three or more test antigens. Seroreactivity was most prevalent to Babesia canis antigen (90%) followed by Babesia gibsoni (75%), Ehrlichia canis (63%), Rickettsia conorii--Moroccan strain (58%), Rickettsia conorii--Israeli strain no. 2 (28%), Borrelia burgdorferi (10%) or Bartonella vinsonii (berkhoffii) (10%). Seroconversion documented in seven dogs, supported an acute phase diagnosis of ehrlichiosis in four dogs, R. conorii infection in three dogs and babesiosis in one dog. In the remaining dogs, correlation of clinical abnormalities with increased seroreactivity was not established through the design of this study. Although Lyme borreliosis has not been reported in people in Israel, Western blot analysis for antibodies reactive to B. burgdorferi identified genus-specific antiflagellin antibodies indicating that dogs in Israel are exposed to a Borrelia species. Identification of species-specific seroreactivity was not possible and infection with a Borrelia species other than B. burgdorferi is likely. Seroreactivity to B. vinsonii (berkhoffii) in dogs outside the USA is reported here for the first time.


Uncovering novel actors in astrocyte-neuron crosstalk in Parkinson's disease: the Wnt/β-catenin signaling cascade as the common final pathway for neuroprotection and self-repair.
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by progressive loss of dopaminergic (DAergic) neuronal cell bodies in the substantia nigra pars compacta and gliosis. The cause and mechanisms underlying the demise of nigrostriatal DAergic neurons are ill-defined, but interactions between genes and environmental factors are recognized to play a critical role in modulating the vulnerability to PD. Current evidence points to reactive glia as a pivotal factor in PD pathophysiology, playing both protective and destructive roles. Here, the contribution of reactive astrocytes and their ability to modulate DAergic neurodegeneration, neuroprotection and neurorepair in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rodent model of PD will be discussed in the light of novel emerging evidence implicating wingless-type mouse mammary tumor virus integration site (Wnt)/β-catenin signaling as a strong candidate in MPTP-induced nigrostriatal DAergic plasticity. In this work, we highlight an intrinsic Wnt1/frizzled-1/β-catenin tone that critically contributes to the survival and protection of adult midbrain DAergic neurons, with potential implications for drug design or drug action in PD. The dynamic interplay between astrocyte-derived factors and neurogenic signals in MPTP-induced nigrostriatal DAergic neurotoxicity and repair will be summarized, together with recent findings showing a critical role of glia-neural stem/progenitor cell (NPC) interactions aimed at overcoming neurodegeneration and inducing neurorestoration. Understanding the intrinsic plasticity of nigrostriatal DAergic neurons and deciphering the signals facilitating the crosstalk between astrocytes, microglia, DAergic neurons and NPCs may have major implications for the role of stem cell technology in PD, and for identifying potential therapeutic targets to induce endogenous neurorepair.


Fluid absorption during percutaneous nephrolithotomy: does it matter?
Large amounts of irrigating fluid are used during percutaneous nephrolithotomy (PCNL). This use may be associated with migrating calculus debris, infection, and fluid absorption. This study evaluated the presence of fluid absorption during PCNL, its clinical and biochemical significance, and maneuvers to reduce it. Fluid absorption during PCNL was evaluated in 148 patients by estimating the expired breath ethanol concentration. Factors thought to affect the amount of fluid absorbed were studied, including the amount of irrigating fluid used, the number of nephrostomy tracts, the presence of a low-pressure system, the presence of existing tracts, and complications such as bleeding or perforation of the pelvicaliceal wall. Fluid absorption was evident in all patients, although no patient had any clinical or biochemical evidence of intraoperative or postoperative electrolyte imbalance. Creating a low-pressure system by using an Amplatz sheath, reducing the amount of irrigating fluid used, and staging the procedure significantly reduced the amount of fluid absorbed. Fluid absorption does take place during PCNL. This may be clinically significant in patients with compromised cardiorespiratory or renal status and in pediatric patients, leading to fluid overload. Using a low-pressure system, reducing the nephroscopy time and the amount of irrigating fluid used, and staging the procedure for large renal stone burdens, especially in the presence of complications such as perforation of the pelvicaliceal system, reduces fluid absorption and avoids volume overload. Fluid absorption may also be associated with both infective and noninfective pyrexia, necessitating adequate preoperative control of urinary infection.


Umbilical hernia of stomach.
Herniation of the stomach through the umbilicus is exceedingly rare with only one case reported in the international literature in the past 40 years. One case of a reducible gastric umbilical hernia, not diagnosed by endoscopy, is reported. Diagnosis was made by double-contrast barium examination after 5 years of symptoms and ineffective treatment. Herniation of the stomach is difficult to diagnose by endoscopy and radiological studies can be more sensitive and allow a more specific diagnosis.


Demoralization in oral cancer inpatients and its association with spiritual needs, quality of life, and suicidal ideation: a cross-sectional study.
Demoralization is a common problem in oral cancer patients owing to the chronic and severe nature of their affliction. However, the association between demoralization and the patient's spiritual needs, quality of life, and suicidal ideation remains unclear. This study aims to provide insights into possible links between demoralization among oral cancer patients and its effects on the patient's spiritual needs, quality of life, and suicidal ideation. We examined 155 Taiwanese oral cancer inpatients in Taichung Veterans General Hospital, Taiwan, using the following three rating scales: (a) Demoralization Scale Mandarin Version (DS-MV), (b) Spiritual Interests Related to Illness Tool, and (c) The Taiwan Chinese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Suicidal ideation was established if at least one of the two suicide-related items on the DS-MV scale were checked. We divided the participants into high- and low-demoralization groups, per the cutoff score of 30. We then explored group associations with sociodemographic features, quality of life, and spiritual needs. Logistic regression and receiver operating characteristic (ROC) curves were used to determine demoralization and its association between these variables. Fifty-five (35.5%) patients were categorized as having high demoralization (DS-MV scale score > 30), with scores for DS-MV for all patients being 27.2 ± 16.8. The rates of suicidal ideation were 29.1% (16/55) in the high-demoralization group and 2% (2/100) in the low-demoralization group, with an odds ratio (95% confidence interval) of 20.10 (4.41-91.55). Logistic regression analysis revealed significant effects of spiritual needs and global health status on the DS-MV scores (p < 0.001). Multivariate analyses further confirmed that only overall quality of life scores < 62.5 and spiritual needs < 3.7 significantly predicted the occurrence of high demoralization. High demoralization is associated with low satisfaction with spiritual needs, poor quality of life, and high risk of suicidal ideation. DS-MV may potentially be an effective tool for achieving holistic health care among oral cancer patients.


Evaluating mercury concentrations and body condition in American alligators (Alligator mississippiensis) at Merritt Island National Wildlife Refuge (MINWR), Florida.
Concentrations of mercury (Hg) are not well studied in free-ranging wildlife. Atmospheric deposition patterns of Hg have been studied in detail and have been modeled for both global and specific locations and often correlate to environmental impact. However, monitoring the impact of Hg deposition in wildlife is complicated due to local environmental conditions that can affect the transformation of atmospheric Hg to the biologically available forms (e.g., rainfall, humidity, pH, the ability of the environment to methylate Hg), as well as affect the accessibility to organisms for sampling. In this study, Hg concentrations in blood samples from a population of American alligators (Alligator mississippiensis) at Merritt Island National Wildlife Refuge (MINWR), FL, USA, over a seven-year period (2007 to 2014; n=174 individuals) were examined to assess Hg variation in the population, as well as the difference in Hg concentration as a function of health status. While most of this population is healthy, 18 individuals with low body mass indices (BMI, defined in this study) were captured throughout the sampling period. These alligators exhibited significantly elevated Hg concentrations compared to their age/sex/season matched counterparts with normal BMI, suggesting that health status should be taken into account when examining Hg concentrations and effects. Alligator blood Hg concentrations were related to the interaction of age/size, sex, and season. This study illustrates the value of a routinely monitored population of large predators in a unique coastal wetland ecosystem, and illuminates the value of long-term environmental exposure assessment.


Reversible bonding of microfluidics: Review and applications.
With the development of microfluidic technology, new materials and fabrication methods have been constantly invented in the field of microfluidics. Bonding is one of the key steps for the fabrication of enclosed-channel microfluidic chips, which have been extensively explored by researchers globally. The main purpose of bonding is to seal/enclose fabricated microchannels for subsequent fluid manipulations. Conventional bonding methods are usually irreversible, and the forced detachment of the substrate and cover plate may lead to structural damage to the chip. Some of the current microfluidic applications require reversible bonding to reuse the chip or retrieve the contents inside the chip. Therefore, it is essential to develop reversible bonding methods to meet the requirements of various applications. This review introduces the most recent developments in reversible bonding methods in microfluidics and their corresponding applications. Finally, the perspective and outlook of reversible bonding technology were discussed in this review.


Evaluation of nasal patency by acoustic rhinometry after repair of complete unilateral cleft lip and palate.
The aim of the current study was to evaluate nasal patency by acoustic rhinometry in children aged 4-8 years with repaired complete unilateral cleft lip and palate (UCLP) compared with an age-matched control group without cleft lip and palate (CLP). This comparative cross-sectional study was conducted at a tertiary care teaching hospital and a private ENT clinic in Porto Alegre, southern Brazil. The case group consisted of 38 children who had undergone surgery for complete UCLP (mean age, 6.44 years), and the control group of 21 children without CLP (mean age, 6.21 years) recruited among patients seeking medical care for ear diseases at the private clinic. Acoustic rhinometry was performed in all children after administration of oxymetazoline hydrochloride (2 × 0.25 mg/mL) for nasal vasoconstriction. The minimal cross-sectional area and nasal volume of the cleft side were smaller than those of the non-cleft side in the case group (p = 0.001). When the two groups were compared, the non-cleft side in the case group did not differ from the control group (p = 0.175), but the minimal cross-sectional area and volume of the cleft nasal cavity were smaller than the mean values of the two nostrils of controls (p = 0.001). In conclusion, our findings show that nasal patency on the cleft side is impaired in children surgically treated for complete UCLP.


Connecting mean field models of neural activity to EEG and fMRI data.
Progress in functional neuroimaging of the brain increasingly relies on the integration of data from complementary imaging modalities in order to improve spatiotemporal resolution and interpretability. However, the usefulness of merely statistical combinations is limited, since neural signal sources differ between modalities and are related non-trivially. We demonstrate here that a mean field model of brain activity can simultaneously predict EEG and fMRI BOLD with proper signal generation and expression. Simulations are shown using a realistic head model based on structural MRI, which includes both dense short-range background connectivity and long-range specific connectivity between brain regions. The distribution of modeled neural masses is comparable to the spatial resolution of fMRI BOLD, and the temporal resolution of the modeled dynamics, importantly including activity conduction, matches the fastest known EEG phenomena. The creation of a cortical mean field model with anatomically sound geometry, extensive connectivity, and proper signal expression is an important first step towards the model-based integration of multimodal neuroimages.


LiCoO2 concaved cuboctahedrons from symmetry-controlled topological reactions.
Morphology control of functional materials is generally performed by controlling the growth rates on selected orientations or faces. Here, we control particle morphology by "crystal templating": by choosing appropriate precursor crystals and reaction conditions, we demonstrate that a material with rhombohedral symmetry-namely the layered, positive electrode material, LiCoO(2)-can grow to form a quadruple-twinned crystal with overall cubic symmetry. The twinned crystals show an unusual, concaved-cuboctahedron morphology, with uniform particle sizes of 0.5-2 μm. On the basis of a range of synthetic and analytical experiments, including solid-state NMR, X-ray powder diffraction analysis and HRTEM, we propose that these twinned crystals form via selective dissolution and an ion-exchange reaction accompanied by oxidation of a parent crystal of CoO, a material with cubic symmetry. This template crystal serves to nucleate the growth of four LiCoO(2) twin crystals and to convert a highly anisotropic, layered material into a pseudo-3-dimensional, isotropic material.


Real-time three-dimensional micro-imaging of liquid front in spreading sessile droplet under transient spreading states.
Dynamic wetting behaviors of sessile droplets on substrates play crucial roles for various industrial chemical processes. In the case of complete wetting, it has been proposed that a precursor film which is nanometer-order thickness and micrometer-order length further expands outside the macroscopic contact line of the sessile droplet. While the time evolution of the precursor film is believed to strikingly affect the macroscopic wetting behavior (e.g., spreading velocity), it had been hard to visualize the three-dimensional shape of the precursor film at the early stage of wetting. Further, although the spreading velocity rapidly decreases upon time at the early stage of the wetting (transient state) and then converged to be a constant at later time (steady state), conventional fluid mechanics theories generally describe only the wetting behavior at the steady state. Therefore, experimental observation of time evolution of the precursor film shape in the transient state is essential to proceed the theories to the next step. Here, a monochromatic laser interference microscope was developed to visualize three-dimensional shape of the wetting front of sessile droplets in real time. By detecting an interference of the laser reflected at the liquid and substrate surfaces, the precursor film was successfully visualized with a time resolution of 20 ms and a thickness resolution of about 3.5 nm at worst. For 10 cSt silicone oil on Si substrate, a 60-nm-thick and 70-μm-long precursor film was observed for 2-10 min after dropping and its spreading velocity which decreased with time was quantitatively analyzed.


G-STRATEGY: Optimal Selection of Individuals for Sequencing in Genetic Association Studies.
In a large-scale genetic association study, the number of phenotyped individuals available for sequencing may, in some cases, be greater than the study's sequencing budget will allow. In that case, it can be important to prioritize individuals for sequencing in a way that optimizes power for association with the trait. Suppose a cohort of phenotyped individuals is available, with some subset of them possibly already sequenced, and one wants to choose an additional fixed-size subset of individuals to sequence in such a way that the power to detect association is maximized. When the phenotyped sample includes related individuals, power for association can be gained by including partial information, such as phenotype data of ungenotyped relatives, in the analysis, and this should be taken into account when assessing whom to sequence. We propose G-STRATEGY, which uses simulated annealing to choose a subset of individuals for sequencing that maximizes the expected power for association. In simulations, G-STRATEGY performs extremely well for a range of complex disease models and outperforms other strategies with, in many cases, relative power increases of 20-40% over the next best strategy, while maintaining correct type 1 error. G-STRATEGY is computationally feasible even for large datasets and complex pedigrees. We apply G-STRATEGY to data on high-density lipoprotein and low-density lipoprotein from the AGES-Reykjavik and REFINE-Reykjavik studies, in which G-STRATEGY is able to closely approximate the power of sequencing the full sample by selecting for sequencing a only small subset of the individuals.


Factors in fish modifying methylmercury toxicity and metabolism.
We report here some results of a long-term (19 month) study with cats fed methylmercury (MeHg) in nutritionally balanced diets based on fish. By using either freshwater pike (low in Se) or canned tuna (high in Se) as the major protein source, basal diets with low levels of MeHg were prepared having different Se content, all Se being of natural origin. The basal diets produced no signs of toxicity or pathological changes over the l9-month period. In cats fed basal diets spiked with medium or high levels of MeHg, evidence for delayed onset of toxic effects from the added MeHg was observed with the tuna diets compared to pike diets. In brain, muscle, and blood, the activity of GSH peroxidase, a selenoenzyme, was decreased by Hg. In liver, substantial accumulation of Hg with Se occured (molar Hg/Se ratio approximately 1.4 to 1.8) but GSH peroxidase activity was unaffected. We suggest that the coaccumulation of Hg and Se in liver measures the extent to which MeHg has been metabolically transformed by metabolism to Hg++, and inactivated by deposition as a Hg/Se complex of low bioavailability. The accumulation of Hg and Se in liver was much greater in cats fed tuna compared to pike, out of proportion to the relatively small differences in Hg and Se content of the tuna and pike basal diets. Some mechanisms are described by which selenium, vitamin E, and other factors might facilitate MeHg breakdown to inorganic Hg during long term low level exposure to MeHg.


The effect of intracellular parasitism on cell phenotype.
Human peritoneal macrophages were harvested from 'long dwell' peritoneal dialysis bags. Adherent cells were harvested after 2 h culture on plastic and these were then exposed to M. lepraemurium (MLM) or latex beads (LB) for further culture periods of 2 and 24 h. Immunophenotyping of the macrophages was performed before and after culture both with and without the addition of MLM or LB. Monoclonal antibodies RFD1, RFD7 and RFD9 were used, which in control tissues recognize dendritic cells, mature macrophages and epithelioid cells respectively. MoAb RFDR1 (HLA-DR) was also used. Results revealed that the addition of MLM or LD for 2 h did not significantly alter the original proportions of RFD1+ and RFD7+ cells. A proportion of both RFD1+ and RFD7+ cells were found to phagocytose both MLM and LB, although RFD7+ cells seemed slightly more efficient. After 24 h culture with MLM reduced numbers of cells expressed the RFD1+ marker while increased numbers of cells expressing RFD7+ antigen were present. A concurrent small rise in the proportion of RFD7+ cells parasitized implied that this increase was due to RFD1+ cells becoming RFD7+ cells. Culture for 24 h with MLM significantly reduced the percentage of total cells expressing HLA-DR. Conversely, 24 h culture with MLM was shown to increase the proportion of cells expressing the epithelioid cell marker RFD9. These results suggest that intracellular parasitism may affect the expression of surface antigens on cells and by implication thus affect cell function.


Vitamin D-induced vitamin D receptor expression induces tamoxifen sensitivity in MCF-7 stem cells via suppression of Wnt/β-catenin signaling.
Objective: Cancer stem cells (CSCs) are responsible for the drug resistance of breast cancers. Vitamin D deficiency promotes tumor resistance. The present study examined the effect of vitamin D and vitamin D receptor (VDR) expression on the tamoxifen resistance of CSCs. Methods: MCF-7 cells were treated with 1,25(OH)2D3 and their levels of VDR expression, viability, and apoptosis were detected. CD133+ MCF-7 stem cells were identified and transfected with a VDR-overexpression plasmid. The tamoxifen concentration that reduced MCF-7 cell viability by 50% (IC50) was determined. The activation of Wnt/β-catenin signaling was also investigated. Results: Vitamin D reduced the viability of MCF-7 cells and promoted their apoptosis. Vitamin D enhanced VDR expression and induced DNA damage. When CD133+ stem cells were separated from MCF-7 cells, the IC50 of tamoxifen for stem cells was significantly higher than that of parental MCF-7 cells, suggesting a higher tamoxifen resistance in MCF-7 stem cells. Levels of VDR expression and Wnt/β-catenin signaling in CD133+ cells were markedly lower and higher than those in CD133- cells, respectively. Stem cells transfected with VDR overexpression plasmids showed decreased tamoxifen IC50 values, viability, spheroid formation, and expression of Wnt and β-catenin proteins when compared with control cells. Cell apoptosis was increased by transfection with a VDR overexpression plasmid. Finally, the inhibitory effects induced by VDR overexpression could be reversed by the VDR inhibitor, calcifediol. Conclusion: Stem cells contributed to the tamoxifen resistance of MCF-7 cells. Vitamin D-induced VDR expression increased the sensitivity of MCF-7 stem cells to tamoxifen by inhibiting Wnt/β-catenin signaling.


Opioid modulation of oxytocin release.
Analgesia or anesthesia is frequently used for women in labor. A wide range of opioid analgesics with vastly different pharmacokinetics, potencies, and potential side effects can be considered by physicians and midwives for laboring patients requesting pain relief other than a labor epidural. The past 50 years have seen the use of the classic mu opioid agonist morphine and other opioids diminish markedly for several reasons, including availability of epidural anesthetics, side effects, formulary restrictions, and concern for neonatal respiratory depression. Morphine is now primarily used in obstetrics to provide rest and sedation as appropriate for the stressed prodromal stages of a labor without sufficient cervical dilatation. This review discusses the scientific basis for opioid modulation of oxytocin release from the posterior pituitary and the practical implications of this relationship to explain well-known clinical observations of the effect of morphine on prodromal labor.


Psychometric properties of the system for coding couples' interactions in therapy--alcohol.
Few systems are available for coding in-session behaviors for couples in therapy. Alcohol Behavioral Couple Therapy (ABCT) is an empirically supported treatment, but little is known about its mechanisms of behavior change. In the current study, an adapted version of the Motivational Interviewing for Significant Others coding system was developed into the System for Coding Couples' Interactions in Therapy-Alcohol (SCCIT-A), which was used to code couples' interactions and behaviors during ABCT. Results showed good interrater reliability of the SCCIT-A and provided evidence that the SCCIT-A may be a promising measure for understanding couples in therapy. A 3-factor model of the SCCIT-A (Positive, Negative, and Change Talk/Counter-Change Talk) was examined using a confirmatory factor analysis, but model fit was poor. Because model fit was poor, ratios were computed for Positive/Negative ratings and for Change Talk/Counter-Change Talk codes based on previous research in the couples and Motivational Interviewing literature. Post hoc analyses examined correlations between specific SCCIT-A codes and baseline characteristics, and indicated some concurrent validity. Correlations were run between ratios and baseline characteristics; ratios may be an alternative to using the factors from the SCCIT-A. Reliability and validity analyses suggest that the SCCIT-A has the potential to be a useful measure for coding in-session behaviors of both partners in couples therapy and could be used to identify mechanisms of behavior change for ABCT. Additional research is needed to improve the reliability of some codes and to further develop the SCCIT-A and other measures of couples' interactions in therapy.


PFAPA syndrome in children evaluated for tonsillectomy.
Among 40 children undergoing tonsillectomy for recurrent pharyngitis, 15 (37.5%) had presented preoperatively with complaints compatible with PFAPA syndrome. All 15 had had periodic fever every three to four weeks and pharyngitis; 12 (80%) had cervical adenitis and five (33%) aphthous stomatitis. All children had been well between episodes and showed a dramatic postoperative improvement. PFAPA syndrome is not uncommon among children having tonsillectomy. Tonsillectomy is curative in most of these patients.


Errors of insulin therapy: Real-life experiences from developing world.
A significant bulk of people living with diabetes is on insulin therapy aiming for satisfactory glycemic control and resultant reduction in vascular complications of diabetes. Insulin undoubtedly is the most potent antihyperglycemic agent. However, a significant proportion of insulin-treated diabetics fails to achieve the desired glycemic goal. Errors of insulin therapy remain an important and correctable factor in many of them. Such errors of insulin therapy can potentially arise at each and every step starting from the office of the clinicians while prescribing it for the first time up to the point of administration. Here, we share some of our clinical experiences on potential errors of insulin therapy and discuss preventive measures to overcome these simple barriers to achieve long-term glycemic control. We believe, these unfortunate but interesting scenarios, though rampant in the developing world may not be uncommon in the other parts of the world if carefully looked for. It is important for the clinicians to learn from these experiences with insulin therapy because it represents, for a majority of patients, the last option in our therapeutic armamentarium.


Low-temperature solution-processed perovskite solar cells with high efficiency and flexibility.
Perovskite compounds have attracted recently great attention in photovoltaic research. The devices are typically fabricated using condensed or mesoporous TiO2 as the electron transport layer and 2,2'7,7'-tetrakis-(N,N-dip-methoxyphenylamine)9,9'-spirobifluorene as the hole transport layer. However, the high-temperature processing (450 °C) requirement of the TiO2 layer could hinder the widespread adoption of the technology. In this report, we adopted a low-temperature processing technique to attain high-efficiency devices in both rigid and flexible substrates, using device structure substrate/ITO/PEDOT:PSS/CH(3)NH(3)PbI(3-x)Cl(x)/PCBM/Al, where PEDOT:PSS and PCBM are used as hole and electron transport layers, respectively. Mixed halide perovskite, CH(3)NH(3)PbI(3-x)Cl(x), was used due to its long carrier lifetime and good electrical properties. All of these layers are solution-processed under 120 °C. Based on the proposed device structure, power conversion efficiency (PCE) of 11.5% is obtained in rigid substrates (glass/ITO), and a 9.2% PCE is achieved for a polyethylene terephthalate/ITO flexible substrate.


Operation RUMAN and the Ministry of Defence response to Hurricane Irma.
Operation RUMAN was the British government's combined military and humanitarian operations in September 2017 to provide relief to the British Overseas Territories in the Caribbean affected by Hurricane Irma. The Ministry of Defence (MoD), in conjunction with the Department for International Development, produced a tangible effect by the delivery of healthcare and a response to a humanitarian disaster with very little time for planning. The rescue element was accomplished within days but this was followed swiftly by a recovery phase requiring a 'whole force approach', with additional assets from non-governmental organisations and the private sector. The aim of this article is to provide information on the role of the Defence Medical Services on behalf of the MoD, and other departmental organisations in achieving the mission of providing medical and logistical support for these British Overseas Territories.


Suckers or saviors? Consistent contributors in social dilemmas.
Groups and organizations face a fundamental problem: They need cooperation but their members have incentives to free ride. Empirical research on this problem has often been discouraging, and economic models suggest that solutions are unlikely or unstable. In contrast, the authors present a model and 4 studies that show that an unwaveringly consistent contributor can effectively catalyze cooperation in social dilemmas. The studies indicate that consistent contributors occur naturally, and their presence in a group causes others to contribute more and cooperate more often, with no apparent cost to the consistent contributor and often gain. These positive effects seem to result from a consistent contributor's impact on group members' cooperative inferences about group norms.


Evaluation of postoperative surveillance strategies for esophago-gastric cancers in the UK and Ireland.
Esophago-gastric malignancies are associated with a high recurrence rate; yet there is a lack of evidence to inform guidelines for the standardization and structure of postoperative surveillance after curatively intended treatment. This study aimed to capture the variation in postoperative surveillance strategies across the UK and Ireland, and enquire the opinions and beliefs around surveillance from practicing clinicians. A web-based survey consisting of 40 questions was sent to surgeons or allied health professionals performing or involved in surgical care for esophago-gastric cancers at high-volume centers in the UK. Respondents from each center completed the survey on what best represented their center. The first section of the survey evaluated the timing and components of follow-ups, and their variation between centers. The second section evaluated respondents perspective on how surveillance can be structured. Thirty-five respondents from 27 centers consisting 28 consultants, 6 senior trainees and 1 specialist nurse had completed the questionnaire; 45.7% of responders arranged clinical follow-up at 2-4 weeks. Twenty responders had a specific postoperative surveillance protocol for their patients. Of these, 31.4% had a standardized protocol for all patients, while 25.7% tailored it to patient needs. Patient preference, comorbidities and chance of recurrence were considered as major factors for necessitating more intense surveillance than currently practiced. There is a significant variation in how patients are monitored after surgery between centers in the UK. Randomized controlled trials are necessary to link surveillance strategies to both survival outcomes and quality of life of patients and to evaluate the prognostic value of different postoperative surveillance strategies.


Context-independent directional cue learning by hippocampal place cells.
In a symmetrical environment possessing no other polarizing visual cues, the spatially localized firing of hippocampal place cells can be primarily orientated by a reliable distal visual stimulus, such as a white cue card. However, if such a directional cue is made unreliable by being frequently moved in full view of the rat, the rat's internal sense of direction comes, over the course of a few days, to control the orientation of place fields instead. We investigated whether this simple form of 'cue-instability' learning would transfer to a new context, in which the firing patterns of the place cells become reorganized and in which a new spatial representation is thus active. We found that after cue-instability learning, the 'remapped' place field representation in the new environment was also orientated by the internal sense of direction of the rat rather than by the cue card, showing that the cue learning generalized from one context (and hence spatial representation) to another. This contrasts with another kind of place cell learning, in which the cells can acquire the ability to discriminate two spatial locations in one context but do not transfer this discrimination to a new context. We discuss the different effects of context changes on learned place cell activity in terms of the possible architecture of the inputs to place cells.


Clinical outcomes of prenatally diagnosed cases of isolated and nonisolated pericardial effusion.
The purpose of this study was to investigate the clinical outcome of fetal pericardial effusion (PE). This study involved a retrospective review of prenatally diagnosed PE cases. The criterion for inclusion was pericardial fluid in an area greater than 2 mm in diameter. A total of 276 cases of PE and 252 cases diagnosed with other anomalies were initially reviewed. PE is associated with cardiac malformation, hydrops fetalis, extracardiac abnormalities, infections, anemias, intrauterine growth restriction, and aneuploidy markers in fetuses. Of these reviewed cases, 24 cases of isolated fetal PE were studied. In all cases, pericardial fluid filled an area ranging from 2 to 17 mm in diameter. Four cases of isolated PE had an abnormal postnatal condition, and 3 cases were excluded due to lack of follow-up. The size of the PE was not related to the regression of pericardial fluid, adverse outcomes or mortality rate associated with the isolated PE. All newborns were healthy, and there were no chromosomal abnormalities in the study population. There were no adverse clinical outcomes or chromosomal abnormalities in the fetuses diagnosed with isolated PE. Most cases of isolated PE resolved spontaneously and were associated with a good prognosis.


[The significance of innate immunity in juvenile idiopathic arthritis].
For years it was thought that the disorder of adaptive immunity is critical in the pathogenesis of juvenile idiopathic arthritis (JIA). However, the results of recent studies emphasize the importance of innate immunity and especially the role of alarmins, a group of multifunctional proteins that are released into the intercellular space during tissue injury or inflammation, mobilizing and activating the cells of innate immunity. These data indicate that inflammation triggered by alarmins plays a role in the pathogenesis of JIA. Furthermore, alarmins may serve as inflammatory markers and targets of therapy.


Antimicrobial resistance patterns and prevalence of class 1 and 2 integrons in Shigella flexneri and Shigella sonnei isolated in Uzbekistan.
Shigella is a frequent cause of bacterial dysentery in the developing world. Treatment with effective antibiotics is recommended for shigellosis, but options become limited due to globally emerging resistance. One of the mechanisms for the development of resistance utilizes integrons. This study described the antibiotic susceptibility and the presence of class 1 and 2 integrons in S. flexneri and S. sonnei isolated in Uzbekistan. We studied 31 isolates of S. flexneri and 21 isolates of S. sonnei isolated in Uzbekistan between 1992 and 2007 for the susceptibility or resistance to ampicillin (Am), chloramphenicol (Cl), tetracycline (Te), co-trimoxazole (Sxt), kanamycin (Km), streptomycin (Str), gentamicin (Gm), cefazolin (Czn), cefoperazone (Cpr), cefuroxime (Cur), ceftazidime (Ctz), nalidixic acid (NA) and ciprofloxacin (Cip). Am/Str/Cl/Te and Am/Str/Cl/Te/Sxt resistance patterns were found most frequently in S. flexneri. Single isolates were resistant to aminoglycoside, quinolones and cephalosporins. The resistance patterns were different in the two species. Integrons were detected in 93.5% of S. flexneri (29/31) and 81.0% of S. sonnei (17/21) isolates. In addition, 61.3% of S. flexneri (19/31) isolates and 19.0% of S. sonnei (4/21) isolates carried both classes of integrons. In 29.0% of S. flexneri (9/31) isolates, only class 1 integrons were identified. In S. flexneri isolates, the presence of class 1 integrons was associated with resistance to ampicillin and chloramphenicol. Only Class 2 integrons were present in 61.9% of S. sonnei (13/21) isolates. Our study documents antibiotic resistance among Shigella spp. in Uzbekistan. Ninety percent of Shigella strains were resistant to previously used antibiotics. Differences among S. flexneri and S. sonnei isolates in patterns of antimicrobial resistance to routinely used shigellosis antibiotics were observed. The majority of S. flexneri were resistant to ampicillin, chloramphenicol, tetracycline and streptomycin. Class 1 and 2 integrons were widely present in these Shigella strains. Resistance to ampicillin/chloramphenicol was associated with the presence of class 1 integrons. Though several mechanisms are possible, the resistance of Shigella isolates to ampicillin/chloramphenicol may be associated with the expression of genes within class 1 integrons.


Role of TRPV1 and P2X receptors in the activation of lung vagal C-fiber afferents by inhaled cigarette smoke in rats.
Inhaled cigarette smoke (CS) triggers airway reflexes that are thought to result from the activation of lung vagal C-fiber afferents (LVCAs) via the action of reactive oxygen species in rats. We investigated the role of transient receptor potential vanilloid 1 (TRPV1) and P2X receptors in LVCA activation. Activities of LVCAs were recorded in anesthetized and artificially ventilated rats. Airway challenge of CS produced a concentration-dependent fiber stimulation. Pretreatment with dimethylthiourea [DMTU; a scavenger of hydroxyl radical (OH)], capsazepine (CPZ; a TRPV1 receptor antagonist) and iso-pyridoxalphosphate-6-azophenyl-2',5'-disulphonate (iso-PPADS; a P2X receptor antagonist) separately reduced the fiber responses by 64, 40 and 44%, respectively, whereas pretreatment with hexamethonium (a nicotinic acetylcholine receptor antagonist) failed to alter the response. A combination of CPZ and iso-PPADS exerted a greater inhibitory effect compared with the effect of either single pretreatment. However, a combination of DMTU, CPZ and iso-PPADS did not further reduce the fiber response compared with the combined effect of CPZ and iso-PPADS. It was concluded that both TRPV1 and P2X receptors, but not nicotinic acetylcholine receptors, participate in the stimulation of LVCAs by inhaled CS, possibly through the action of OH.


Rooted tRNAomes and evolution of the genetic code.
We advocate for a tRNA- rather than an mRNA-centric model for evolution of the genetic code. The mechanism for evolution of cloverleaf tRNA provides a root sequence for radiation of tRNAs and suggests a simplified understanding of code evolution. To analyze code sectoring, rooted tRNAomes were compared for several archaeal and one bacterial species. Rooting of tRNAome trees reveals conserved structures, indicating how the code was shaped during evolution and suggesting a model for evolution of a LUCA tRNAome tree. We propose the polyglycine hypothesis that the initial product of the genetic code may have been short chain polyglycine to stabilize protocells. In order to describe how anticodons were allotted in evolution, the sectoring-degeneracy hypothesis is proposed. Based on sectoring, a simple stepwise model is developed, in which the code sectors from a 1→4→8→∼16 letter code. At initial stages of code evolution, we posit strong positive selection for wobble base ambiguity, supporting convergence to 4-codon sectors and ∼16 letters. In a later stage, ∼5-6 letters, including stops, were added through innovating at the anticodon wobble position. In archaea and bacteria, tRNA wobble adenine is negatively selected, shrinking the maximum size of the primordial genetic code to 48 anticodons. Because 64 codons are recognized in mRNA, tRNA-mRNA coevolution requires tRNA wobble position ambiguity leading to degeneracy of the code.


Covalent versus Charge Transfer Modification of Graphene/Carbon-Nanotubes with Vitamin B1: Co/N/S-C Catalyst toward Excellent Oxygen Reduction.
High-performance nonprecious cathodic catalysts for oxygen reduction are highly demanded for low-temperature polymer electrolyte membrane fuel cells (PEMFCs). Here, we report a noble-meta- free, nitrogen and sulfur codoped graphene(G)/carbon-nanotube(CNT) material decorated with Co nanoparticles (NPs), which serve as catalytic sites for excellent oxygen reduction reaction (ORR) in basic and acidic media. Out of the cathodic catalysts synthesized by either covalent (cov) or charge transfer (CT) modification of graphen oxide (GO) with thiamine (Th: Vitamin B1), ThG/CNT/Co-cov shows more promising ORR properties than ThG/CNT/Co-CT. Catalyst ThG/CNT/Co-cov exhibits onset/halfwave potentials of 0.95/0.86 V in 0.1 M KOH and 0.92/0.83 V in 0.1 M HClO4, which are comparable to those of commercial catalyst Pt/C (0.95/0.86 V). As compared to Pt/C, our catalyst shows higher current densities of 6.72 mA cm(-2) in basic medium and 7.08 mA cm(-2) in acidic medium at 0.55 V (vs reversible hydrogen electrode (RHE)). It also exhibits better catalytic stability and methanol tolerance. High catalytic efficiency and stability of ThG/CNT/Co-cov show a promising prospect of materialization of PEMFCs for clean energy production.


Treatment of First-Time Perianal Abscess in Childhood, Balance Recurrence and Fistula Formation Rate with Medical Intervention.
Because of differences in therapy for first-time perianal abscess, a wide range of recurrences and/or development of fistula-in-ano (RF) rates have been reported. The indication for determining when surgical intervention is needed remains obscure and controversial. This retrospective study sought to compare outcomes of conservative treatment with those after incision and drainage (ID) to determine the optimal time for surgical intervention. A total of 697 patients with first-time perianal abscess were included in this study. The median patient age at the time of onset was 129 days (range: 5-5,110 days). The median follow-up period was 395 days (range: 120-760 days). Of the 697 patients with first-time perianal abscess, 355 (50.9%) patients who received conservative treatment had 12.7% (45/355) RF rate, which is less than that of abscesses treated with ID (24.6%, 72/297; p < 0.001). The median course was 23 (2,466) days, which did not differ significantly from that of abscesses with ID (18 [3,510] days) (p = 0.609). Forty-six (6.6%) patients with abscesses that perforated spontaneously had 10.9% (5/46) RF rate, which was less than that of abscesses with ID (p = 0.019), and the median course was 9 (3,316) days, which was shorter than that of abscesses with ID (p = 0.04). Conservative treatment is a safe and effective technique for most first-time perianal abscesses with less recurrence and a lower fistula formation rate. Incision must be performed when an abscess is likely to spread or shows no sign of spontaneous perforation.


Choosing to engage and choosing to persist: The role of non-specific factors in health-promoting activities.
Non-specific factors play an important role in determining benefits from health-promoting activities. Previous studies have focussed on beneficial outcomes of motivation during engagement. There are two aims of this project. First, we investigated whether expectancy and intrinsic motivation influence people's decisions to engage with health-promoting activities in the first instance and then subsequently adhere to them. Second, we examined the effects of providing information on health-promoting activities as a method of influencing expectancy and intrinsic motivation. In two studies, participants were informed about a health-promoting activity (Study 1: A breathing exercise for well-being; Study 2: A gratitude exercise for smoking cessation) and told that it has either a 'known' or 'unknown' effectiveness. Participants were then given the opportunity to engage with the activity over the following days. Expectancy and intrinsic motivation were measured after reading the information and prior to engagement with the activity. Adherence to the activity was measured at follow-up. In both studies, intrinsic motivation positively predicted willingness to engage with the activities as well as subsequent adherence. Expectancy predicted adherence in Study 1 and choices to engage in Study 2, but not after controlling for intrinsic motivation. Describing the gratitude exercise as having a known effectiveness in Study 2 enhanced motivation and adherence to the activity. The non-specific benefit brought by intrinsic motivation plays an important role in choosing to engage with health-promoting activities as well as subsequent adherence. Our results also show that simple statements about the potential benefits of a health-promoting activity can motivate engagement and adherence. Statement of contribution What is already known on this subject? Previous studies have established that non-specific factors, namely expectancies and intrinsic motivation, play an important role in determining benefit when engaging in health-promoting activities. These studies have neglected how non-specific factors relate to initial choices to engage in health-promoting activities in the first instance. Intrinsic motivation has been found to be more strongly related to benefit than expectancies in real-world health-promoting activities. What does this study add? Intrinsic motivation predicts choices to engage with a health-promoting activity. Simple statements about benefits of a health-promoting activity motivate engagement.


[Method and evaluation of experimental retinal reattachment].
An animal model of retinal reattachment is needed to study experimental macular relocation and recovery of reattached retina. The purpose of this study was to develop and evaluate a simple technique of retinal reattachment. We used the right eye of 13 pigmented rabbits for this experiment. 3 weeks before the operation, the eyes underwent a gas induced vitreous compression with sulfur hexafluoride gas. Transcleral subretinal hydrodissecction was used to create a partial (60-70% of the whole retina) retinal detachment. Retinal reattachment was observed in ten eyes 18 hours after the operation. The dark-adapted electroretinograms (ERGs) were recorded in 3 rabbits from 3 days to 3 months after the surgery. Selected eyes were enucleated for histology. The amplitude of ERGs (a-wave and b-wave) were reduced to 30% and 40% of the control eyes on day 3. These waves were restored up to 70% and 80% of normal at 2 weeks and showed no significant changes thereafter. Degeneration and loss of photoreceptors in the early days after surgery as seen by light microscopy were almost completely restored to normal at 3 months after surgery. This model provides large retinal detachment and reattachment with minimized inflammatory response.