Screening developmentally disabled male populations for fragile X: the effect of sample size.
The fra(X) or Martin-Bell syndrome is the most common cause of inherited mental retardation (MR) in males. It is also associated with a variety of unusual behavioral and developmental disorders. Recent studies found great variability in the estimated strength of association between "autism" and the fra(X) syndrome, but not between MR and fra(X). We examined 31 studies which investigated the association of fra(X) syndrome with either MR or "autism" and found that the conclusion of those researchers could be significantly affected by sample size. Different behavioral and cytogenetic protocols will also influence the strength of association between fra(X) and autism.


Cognitive impairment of Alzheimer disease.
The clinical signs of Alzheimer Disease can be quantitated and correlated with neuropathological evidence of the disease. These clinical signs which include amnesia, aphasia and apraxia can be screened for using instruments such as the Mini-Mental State Exam. In addition, each of these cognitive functions can be quantitated using specific tests. Standardized scores are available for a mini mental state but further research is needed to develop normative data for more detailed psychological assessment tests of specific cognitive deficits. The fact that the cognitive impairment predicts the neuropathology and also the presence of a familial disorder, provides the basis for the validity of these characteristic cognitive signs and the rationale for developing more standardized versions of these tests.


Diagnostic tools for glaucoma detection and management.
Early diagnosis of glaucoma is critical to prevent permanent structural damage and irreversible vision loss. Detection of glaucoma typically relies on examination of structural damage to the optic nerve combined with measurements of visual function. To aid the clinician in evaluation of visual function and structure, computer-based devices such as confocal scanning laser ophthalmoscopy, scanning laser polarimetry, and optical coherence tomography provide quantitative assessments of structural damage, and visual function testing includes standard automated perimetry as well as selective techniques, including short-wavelength automated perimetry and frequency-doubling technology perimetry are available. This article will review current literature on diagnostic modalities available for glaucoma with emphasis on the best evidence available in the literature to support their use in clinical practice.


Unequal pupils: Understanding the eye's aperture.
Unequal pupils (anisocoria) may be physiological, pathological or pharmacological. Importantly, anisocoria can indicate underlying disease of the eye, orbit, brain, neck or chest. Examination of the pupils is therefore a crucial part of any eye examination. As a clinician, it is important to determine whether a patient with anisocoria can be reassured or requires referral for further investigation. This review examines the anatomy of the pupillary pathway, and provides a structured approach to examination of the pupils. The aim is to provide clinicians with confidence when encountering patients with anisocoria. Anisocoria can imply serious underlying pathology, so accurate pupil testing and astute observation are paramount. This review discusses the differential diagnosis of a large pupil (anisocoria more obvious in the light) and a small pupil (anisocoria more obvious in the dark), and discusses the relevant afferent pupillary defect, in which there is no anisocoria but both pupils react differently depending on which eye is illuminated.


The Roles of Junctional Adhesion Molecules (JAMs) in Cell Migration.
The review briefly summarizes the role of the family of adhesion molecules, JAMs (junctional adhesion molecules), in various cell migration, covering germ cells, epithelial cells, endothelial cells, several leukocytes, and different cancer cells. These functions affect multiple diseases, including reproductive diseases, inflammation-related diseases, cardiovascular diseases, and cancers. JAMs bind to both similar and dissimilar proteins and take both similar and dissimilar effects on different cells. Concluding relevant results provides a reference to further research.


Re-visioning public health ethics: a relational perspective.
Canada is in the forefront of thinking about the unique and complex issues of contemporary public health ethics. However, an inordinate focus on the urgent issues of emergency preparedness in pandemic and reliance on bioethical analysis steeped in the autonomy and individual rights tradition of health care and research do not serve adequately as the basis for an ethic of public health with its focus on populations, communities and the common good. This paper describes some concerns regarding the focus on pandemic ethics in isolation from public health ethics; identifies inadequacies in the dominant individualistic ethics framework; and summarizes nascent work on the concepts of relational autonomy, relational social justice and relational solidarity that can inform a re-visioning of public health ethics. While there is still much work to be done to further refine these principles, they can help to reclaim and centre the common and collective good at risk in pandemic and other emergency situations. Minimally, these principles require a policy-making process that is truly transparent, fair and inclusive; is sensitive and responsive to the workings of systemic inequalities; and requires public recognition of the fact that we enter any crisis with varying degrees of inequity. Public policy response to crisis must not forseeably increase existing inequities.


Association between adiposity after diagnosis of prostate cancer and mortality: systematic review and meta-analysis.
To explore the associations between adiposity indices, assessed at or after a diagnosis of prostate cancer, and mortality. Systematic review and meta-analysis. PubMed and Embase, from inception to 16 November 2022. Cohort studies or randomised controlled trials of men with a diagnosis of prostate cancer that investigated the associations between adiposity (body mass index, waist and hip circumference, waist-to-hip ratio, and subcutaneous and visceral adipose tissue) after diagnosis and mortality outcomes. A modified version of the risk of bias for nutrition observational studies tool was used to assess risk of bias. 79 studies were identified that investigated adiposity indices after a diagnosis of prostate cancer in relation to mortality. No randomised controlled trials were found. A non-linear dose-response meta-analysis indicated a J shaped association between body mass index and all cause mortality (33 910 men, 11 095 deaths, 17 studies). The highest rate of all cause mortality was found at the lowest and upper range of the distribution: 11-23% higher rate for a body mass index of 17-21 and 4-43% higher rate for a body mass index of 30-40. The association between body mass index and mortality specific to prostate cancer was flat until body mass index reached 26-27, and then increased linearly by 8-66% for a body mass index of 30-40 (33 137 men, 2947 deaths, 13 studies), but the 95% confidence intervals were wide. These associations did not differ in most predefined subgroups by study design, number of deaths, anthropometric assessment, follow-up time, geographical location, prostate cancer risk group, and adjustment variables. No associations were found in meta-analyses between 10 cm increases in waist circumference and all cause mortality or mortality specific to prostate cancer, but only three studies were available. The few studies with data on change in weight, waist-to-hip ratio, and subcutaneous and visceral adipose tissue reported conflicting results. This review suggests that patients with prostate cancer might benefit from maintaining a healthy weight and avoiding obesity. Future studies should investigate adiposity across different stages of cancer survivorship and use various parameters for distribution of adipose tissue. Open Science Framework https://osf.io/qp3c4.


L-Tyrosine availability affects basal and stimulated catecholamine indices in prefrontal cortex and striatum of the rat.
We previously found that L-tyrosine (L-TYR) but not D-TYR administered by reverse dialysis elevated catecholamine synthesis in vivo in medial prefrontal cortex (MPFC) and striatum of the rat (Brodnik et al., 2012). We now report L-TYR effects on extracellular levels of catecholamines and their metabolites. In MPFC, reverse dialysis of L-TYR elevated in vivo levels of dihydroxyphenylacetic acid (DOPAC) (L-TYR 250-1000 μM), homovanillic acid (HVA) (L-TYR 1000 μM) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (L-TYR 500-1000 μM). In striatum L-TYR 250 μM elevated DOPAC. We also examined L-TYR effects on extracellular dopamine (DA) and norepinephrine (NE) levels during two 30 min pulses (P2 and P1) of K+ (37.5 mM) separated by t = 2.0 h. L-TYR significantly elevated the ratio P2/P1 for DA (L-TYR 125 μM) and NE (L-TYR 125-250 μM) in MPFC but lowered P2/P1 for DA (L-TYR 250 μM) in striatum. Finally, we measured DA levels in brain slices using ex-vivo voltammetry. Perfusion with L-TYR (12.5-50 μM) dose-dependently elevated stimulated DA levels in striatum. In all the above studies, D-TYR had no effect. We conclude that acute increases within the physiological range of L-TYR levels can increase catecholamine metabolism and efflux in MPFC and striatum. Chronically, such repeated increases in L-TYR availability could induce adaptive changes in catecholamine transmission while amplifying the metabolic cost of catecholamine synthesis and degradation. This has implications for neuropsychiatric conditions in which neurotoxicity and/or disordered L-TYR transport have been implicated.


Immunoregulation by cytokines.
The study of cytokine biology relevant to the in vivo (patho)physiology of the immune response is complicated by a series of features inherent to the cytokine system. The present survey focuses on the mechanisms governing the function of cytokines that may give rise to methodological and conceptual problems concerning in vivo manipulations of immunologically relevant cytokines. Special emphasis is laid on the complex interrelation between individual cytokines (cascades, synergy, anergy, pleiotropism, and redundancy), as well as on the mechanisms that guarantee a compartmentalization of cytokines, i.e., a chronological, spatial, cell-type differentiation stage, and activation-dependent restriction of their function. The in vivo effects of cytokines can be studied either by augmenting their concentration or reducing their bioavailability. The advantages of local and systemic cytokine injections, usage of transgenes, or expression as gene products encoded by recombinant viruses are discussed and contrasted with different manipulations provoking cytokine deficiencies, namely the application of cytokine antagonists, neutralizing antibodies and receptor derivates, receptor-targeted cytotoxic drugs, and germ line disruption of cytokine genes. Both types of intervention are afflicted with major problems. Whereas providing an excess of cytokines in vivo, especially at the systemic level, constitutes an essentially non-physiological intervention, the induction of cytokine deficiencies will only unravel essential effects, but is incapable of elucidating the many pleiotropic cytokine effects that, by virtue of the redundancy of the system, compensate for each other.


The Prognostic Significance of FoxP3+ T Cells and CD8+ T Cells in Colorectal Carcinomas.
Recent studies report that tumor microenvironment effects prognosis of colorectal cancers. We analyzed the densities of FoxP3+ cells and CD8+ cells, the ratio of FoxP3+/CD8+ cells and the relationship between these parameters, clinicopathological features, and prognosis. A total of 186 colorectal adenocarcinoma were evaluated in terms of clinicopathological features. Immunohistochemically, densities of intratumoral (IT; IT-FoxP3) and nontumoral (NT; NT-FoxP3) FoxP3+ cells and IT-CD8 and NT-CD8 CD8+ cells were calculated. The ratio of Foxp3/CD8 was recorded. IT-FoxP3 and the ratio of IT-FoxP3/IT-CD8 were higher than NT-FoxP3 and the ratio of NT-FoxP3/NT-CD8, respectively. In multivariate analysis, high FoxP3+ cell density is the most important predictive marker after clinical stage and surgical margin positivity in disease-free survival and the most important predictive marker after clinical stage in overall survival (OS). Short OS time was correlated with clinical stage, decrease in IT-FoxP3, increasing age, number of metastatic lymph nodes, surgical margin positivity, satellite tumor nodule, medullary carcinoma, and the number of pericolorectal lymph nodes. The ratio of FoxP3/CD8 increased noticeably in the IT area, but no relationship was found with survival. The relationships of the cells with one another in the tumor microenvironment seem to have many secrets. Studies in large series supported by molecular techniques can illuminate those secrets to some extent.


Acute Pancoast's syndrome caused by fungal infection.
Nonmalignant causes of Pancoast's syndrome are extremely rare. The authors report the case of a 32-year-old man, receiving treatment for acute lymphoblastic leukemia, who had a clinical picture resembling that of Pancoast's syndrome. Invasive mucormycosis was diagnosed as the cause of the syndrome at emergency thoracotomy undertaken to control massive hemoptysis. In spite of adequate treatment, the patient died 5 weeks postoperatively of overwhelming sepsis. A review of the literature disclosed only two other similar cases. The authors conclude that the development of Pancoast's syndrome in the immunosuppressed patient should raise suspicion of an invasive fungal infection. A precise early diagnosis may allow successful, specific antifungal therapy to be instituted.


A new method for robust quantitative and qualitative analysis of real-time PCR.
An automated data analysis method for real-time PCR needs to exhibit robustness to the factors that routinely impact the measurement and analysis of real-time PCR data. Robust analysis is paramount to providing the same interpretation for results regardless of the skill of the operator performing or reviewing the work. We present a new method for analysis of real-time PCR data, the maxRatio method, which identifies a consistent point within or very near the exponential region of the PCR signal without requiring user intervention. Compared to other analytical techniques that generate only a cycle number, maxRatio generates several measurements of amplification including cycle numbers and relative measures of amplification efficiency and curve shape. By using these values, the maxRatio method can make highly reliable reactive/nonreactive determination along with quantitative evaluation. Application of the maxRatio method to the analysis of quantitative and qualitative real-time PCR assays is shown along with examples of method robustness to, and detection of, amplification response anomalies.


Mapping the emergence of molecular vibrations mediating bond formation.
Fundamental studies of chemical reactions often consider the molecular dynamics along a reaction coordinate using a calculated or suggested potential energy surface1-5. But fully mapping such dynamics experimentally, by following all nuclear motions in a time-resolved manner-that is, the motions of wavepackets-is challenging and has not yet been realized even for the simple stereotypical bimolecular reaction6-8: A-B + C → A + B-C. Here we track the trajectories of these vibrational wavepackets during photoinduced bond formation of the gold trimer complex [Au(CN)2-]3 in an aqueous monomer solution, using femtosecond X-ray liquidography9-12 with X-ray free-electron lasers13,14. In the complex, which forms when three monomers A, B and C cluster together through non-covalent interactions15,16, the distance between A and B is shorter than that between B and C. Tracking the wavepacket in three-dimensional nuclear coordinates reveals that within the first 60 femtoseconds after photoexcitation, a covalent bond forms between A and B to give A-B + C. The second covalent bond, between B and C, subsequently forms within 360 femtoseconds to give a linear and covalently bonded trimer complex A-B-C. The trimer exhibits harmonic vibrations that we map and unambiguously assign to specific normal modes using only the experimental data. In principle, more intense X-rays could visualize the motion not only of highly scattering atoms such as gold but also of lighter atoms such as carbon and nitrogen, which will open the door to the direct tracking of the atomic motions involved in many chemical reactions.


Parkin mitochondria in the autophagosome.
Narendra et al. (see p. 795 of this issue) have made an exciting new discovery that links the fields of mitochondrial quality control and the genetics of Parkinson's disease (PD). Through an elegant series of high-resolution imaging experiments, they are the first to provide evidence that the PARK2 gene product Parkin is selectively recruited to damaged or uncoupled mitochondria. This recruitment leads to the clearance of the organelles through the autophagosome, demonstrating a primary function for Parkin in the regulation of mitochondrial turnover. This work significantly increases our understanding of PD and provides a new framework for the development of therapeutic interventions.


A cluster randomised feasibility trial evaluating nutritional interventions in the treatment of malnutrition in care home adult residents.
Protein energy malnutrition (PEM) predisposes individuals to disease, delays recovery from illness and reduces quality of life. Care home residents in the United Kingdom are especially vulnerable, with an estimated 30 to 42 % at risk. Evidence for nutritional interventions to address PEM in the care home setting is lacking. Widely used techniques include food-based intervention and/or the use of prescribed oral nutritional supplements. To define outcomes and optimise the design for an adequately powered definitive trial to compare the efficacy of established nutritional interventions in this setting, a cluster randomised feasibility trial with a 6-month intervention was undertaken. Care home residents with or at risk of malnutrition were identified across six UK care home sites from September to December 2013. Homes were cluster randomised to standard care (SC), food-based intervention (FB) or oral nutritional supplement intervention (ONS), for 6 months. Key outcomes were trial feasibility and the acceptability of design, allocated interventions and outcome assessments. Anthropometry, dietary intake, healthcare resource usage and participant-reported outcome measures were assessed at baseline and at 3 and 6 months. All six care homes approached were recruited and retained. Of the 110 residents at risk of malnutrition, 85 % entered the trial, and 68 % completed the 6-month intervention. Pre-specified success criteria for feasibility were met for recruitment and retention, intervention acceptability (resident compliance ≥60 %) and measurement of weight, body mass index (BMI), mid-upper arm circumference and dietary intake (data completeness >80 %). Measurement of handgrip strength and triceps skinfold thickness was not found to be feasible in this population. The 95 % confidence interval (CI) data suggested sensitivity to change in dietary intake for weight, BMI and energy intake between baseline and 3 months when each intervention (FB and ONS) was compared with SC. A definitive trial comparing the efficacy of nutritional support interventions in increasing weight and BMI in malnourished care home residents can be conducted. However, whilst the design was feasible, this trial has highlighted the lack of clinically and patient-relevant outcome measures that are appropriate for use in this setting for both research and clinical practice. In particular, this trial identified a need for a more simple measure of functional status, which considers the limitations of functional tests in the care home population. Current Controlled Trials ISRCTN38047922 , Date assigned: 22 April 2014.


[Swiss research agenda for gerontological nursing].
In Switzerland life expectancy is currently 84 years in women and 79 years in men. By 2030 the number of people over 80 will increase by 83% to 625 000. The need of nursing care in this population is expected to double. In order to ensure high quality care, scientific knowledge generated by nursing research is, therefore, pivotal. Within the framework of a national project, a nursing research agenda has been formulated based on a literature review, expert panels, a national survey, and a consensus conference; seven priorities for clinical nursing research for the years 2007-2017 have been developed. In the field of gerontological nursing twenty-one research priorities have been identified. They include among others interventions to support independent living and autonomy at home or the impact of new technology on nursing care of the elderly. Support for caregivers and the health of caregivers of patients with dementia have to be addressed as well as interventions for specific challenges in the elderly such as fall prevention, delirium, malnutrition, and depression. Pivotal questions in nursing research are concerned with the continuity of nursing care that exceeds institutional and professional boundaries. Moreover, it is recommended that research projects address the impact of political decisions on nursing care and provide knowledge to improve quality in nursing homes and community health care. With this article the first research agenda for gerontological nursing is presented, that is based on the seven priorities of the Swiss Research Agenda for Nursing-SRAN and in turn can be used as a basis for strategic discussion, action plans, and research projects.


Arterial Embolization and Cone-Beam Computed Tomography-Guided Lung Resection for Anomalous Systemic Arterial Blood Supply to Normal Lung: Two Case Reports.
Systemic arterial blood supply to a normal lung is a rare anatomical abnormality. Surgery is usually indicated because this abnormality leads to pulmonary hypertension. Herein, we report our experience and ideas for safe vessel dissection. Case 1 was a woman in her 50s. We performed a left lower lobectomy following percutaneous coil embolization. The aberrant artery with emboli was confirmed intraoperatively by cone-beam computed tomography (CBCT) to safely dissect under thoracoscopic surgery (TS). Case 2 was a man in his 40s. Following percutaneous endovascular plug occlusion, we performed a left partial resection using indocyanine green fluorescence navigation. Intraoperatively, CBCT imaging demonstrated the aberrant artery and exact position of the emboli. This combination technique of interventional radiology and TS with CBCT imaging was considered safe and more secure for the treatment of anomalous systemic arterial blood supply to a normal lung.


Impulsive Choice in Mice Lacking Paternal Expression of Grb10 Suggests Intragenomic Conflict in Behavior.
Imprinted genes are expressed from one parental allele only as a consequence of epigenetic events that take place in the mammalian germ line and are thought to have evolved through intragenomic conflict between parental alleles. We demonstrate, for the first time, oppositional effects of imprinted genes on brain and behavior. Specifically, we show that mice lacking paternal Grb10 make fewer impulsive choices, with no dissociable effects on a separate measure of impulsive action. Taken together with previous work showing that mice lacking maternal Nesp55 make more impulsive choices, this suggests that impulsive choice behavior is a substrate for the action of genomic imprinting. Moreover, the contrasting effect of these two genes suggests that impulsive choices are subject to intragenomic conflict and that maternal and paternal interests pull this behavior in opposite directions. Finally, these data may also indicate that an imbalance in expression of imprinted genes contributes to pathological conditions such as gambling and drug addiction, where impulsive behavior becomes maladaptive.


Robustness and Information Transfer within IL-6-induced JAK/STAT Signalling.
Cellular communication via intracellular signalling pathways is crucial. Expression and activation of signalling proteins is heterogenous between isogenic cells of the same cell-type. However, mechanisms evolved to enable sufficient communication and to ensure cellular functions. We use information theory to clarify mechanisms facilitating IL-6-induced JAK/STAT signalling despite cell-to-cell variability. We show that different mechanisms enabling robustness against variability complement each other. Early STAT3 activation is robust as long as cytokine concentrations are low. Robustness at high cytokine concentrations is ensured by high STAT3 expression or serine phosphorylation. Later the feedback-inhibitor SOCS3 increases robustness. Channel Capacity of JAK/STAT signalling is limited by cell-to-cell variability in STAT3 expression and is affected by the same mechanisms governing robustness. Increasing STAT3 amount increases Channel Capacity and robustness, whereas increasing STAT3 tyrosine phosphorylation reduces robustness but increases Channel Capacity. In summary, we elucidate mechanisms preventing dysregulated signalling by enabling reliable JAK/STAT signalling despite cell-to-cell heterogeneity.


Obstetric causes of stillbirth at low socioeconomic settings.
To determine the obstetric causes for stillbirth in low socio-economic settings. A case-control retrospective study through data analysis was conducted at a tertiary university hospital, from January to June 2008. All pregnant women diagnosed with stillbirth after 28 weeks of gestation were included in the study. They were compared with women who had live birth during the study period. Both groups were identified from the admission, and labour room registers. The risk factors studied were maternal age, parity, gestational age, hypertensive disorders of pregnancy, antepartum haemorrhage, obstructed labour and Prematurity. Stillbirth was defined as foetal death after 28 weeks of gestation. Of the 1011 deliveries in the selected period, there were 100 still births (98/1000 deliveries). Both nulliparity and grand multiparity were significantly associated with stillbirths (p < 0.003 and p < 0.009 respectively). From the binary logistic regression analysis, obstetric factors which were significantly associated with stillbirth were obstructed labour ( OR 16.2, CI 5.5-47), hypertensive disorders (OR 9.6 CI 4-23), abruptio placentae (OR 136, CI 52-356), placenta previa (OR 71, CI 21-230), and preterm labour (OR 15 CI 4-54). Gender was not found significantly associated with stillbirth (p < 0.432) Majority of stillbirths were due to risk factors which can be identified in the antenatal period.


Enhanced Influenza Surveillance Using Telephone Triage and Electronic Syndromic Surveillance in the Department of Veterans Affairs, 2011-2015.
Telephone triage (TT) is a method whereby medical professionals speak by telephone to patients to assess their symptoms or health concerns and offer advice. These services are often administered through an electronic TT system, which guides TT professionals during the encounter through the use of structured protocols and algorithms to help determine the severity of the patients' health issue and refer them to appropriate care. TT is also an emerging data source for public health surveillance of infectious and noninfectious diseases, including influenza. We calculated Spearman correlation coefficients to compare the weekly number of US Department of Veterans Affairs (VA) TT calls with other conventional influenza measures for the 2011-2012 through 2014-2015 influenza seasons, for which there were a total of 35 666 influenza-coded TT encounters. Influenza-coded calls were strongly correlated with weekly VA influenza-coded hospitalizations (0.85), emergency department visits (0.90), influenza-like illness outpatient visits (0.92), influenza tests performed (0.86), positive influenza tests (0.82), and influenza antiviral prescriptions (0.89). The correlation between VA-TT and Centers for Disease Control and Prevention (CDC) national data for weekly influenza hospitalizations, influenza tests performed, and positive influenza tests was also strong. TT correlates well with VA health care use and CDC data and is a timely data source for monitoring influenza activity.


Mesoderm Lineage 3D Tissue Constructs Are Produced at Large-Scale in a 3D Stem Cell Bioprocess.
Various studies have presented different approaches to direct pluripotent stem cell differentiation such as applying defined sets of exogenous biochemical signals and genetic/epigenetic modifications. Although differentiation to target lineages can be successfully regulated, such conventional methods are often complicated, laborious, and not cost-effective to be employed to the large-scale production of 3D stem cell-based tissue constructs. A 3D-culture platform that could realize the large-scale production of mesoderm lineage tissue constructs from embryonic stem cells (ESCs) is developed. ESCs are cultured using our previously established 3D-bioprocess platform which is amenable to mass-production of 3D ESC-based tissue constructs. Hepatocarcinoma cell line conditioned medium is introduced to the large-scale 3D culture to provide a specific biomolecular microenvironment to mimic in vivo mesoderm formation process. After 5 days of spontaneous differentiation period, the resulting 3D tissue constructs are composed of multipotent mesodermal progenitor cells verified by gene and molecular expression profiles. Subsequently the optimal time points to trigger terminal differentiation towards cardiomyogenesis or osteogenesis from the mesodermal tissue constructs is found. A simple and affordable 3D ESC-bioprocess that can reach the scalable production of mesoderm origin tissues with significantly improved correspondent tissue properties is demonstrated.


[Ionized air respiratory rehabilitation technics].
The use of negative charge ionized air as a technique of respiratory rehabilitation has been examined. After some introductory remarks on the biological action of this climatic factor, literature references are reviewed and personal experience reported. The importance of negative ionization of air is stressed, especially in acute and chronic inflammatory forms of the airways.


Laser-Assisted Detection of Metal Nanoparticles in Liquid He-II.
The formation of gas bubbles surrounding laser heated copper nanoparticles in superfluid helium at 1.7 K is observed. Because of the effective light capture by these plasmonic particles and the subsequent heat transfer into the liquid, such bubbles grow within 3 μs to tens of micrometers in size. The Schlieren imaging technique is used to determine the spatial distribution of the nanoparticles in the liquid, and the gas bubble radii are related to the parent nanoparticle size. The presented liquid-phase particle size analysis is validated against atomic force microscopy measurements of nanoparticles deposited from the liquid onto a solid substrate.


Mutagenicity of HPLC fractions from extracts of AAtrex-treated corn.
Crude extracts from maize plants treated with varying concentrations of AAtrex, an s-triazine herbicide, were tested for the induction of gene conversion in a diploid strain of Saccharomyces cerevisiae heteroallelic at two loci. These extracts were then subjected to analysis by higher pressure liquid chromatography (HPLC), and the fractions collected in water, 50% methanol, and 100% methanol were similarly tested. Dose-dependent convertogenic activity observed in the 50% methanol fractions suggested that the mutagen(s) is recovered in this fraction.


Discrimination of Invasive Human Skin Tumor Using an Ultrafast ATP-Proton AND-Gate Probe.
Cancer cells undergo unscheduled proliferation resulting from dysregulation of the cell cycle, and hence, evaluation in tumor is of keen interest to examine the invasiveness and recurrence of cancer in the lesion. Molecular probes capable of discriminating actively growing tumor from resting ones remain unexplored despite their vast importance. Here, we describe a novel strategy to visualize invasive areas in tumor with a fluorescence probe that implements synergistic fluorescence response toward the slightly acidic environment of tumor and an ATP-abundant nature of actively growing cells. The probe has been designed for ultrafast detection of ATP with high specificity. We demonstrate its utility in visualizing invasive areas in tumor by distinguishing basal cell carcinomas and squamous cell carcinomas at their early stages by two-photon microscopy.


HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation.
Eighteen histone deacetylases (HDACs) are present in humans, categorized into two groups: zinc-dependent enzymes (HDAC1-11) and NAD(+)-dependent enzymes (sirtuins 1-7). Among zinc-dependent HDACs, HDAC6 is unique. It has a cytoplasmic localization, two catalytic sites, a ubiquitin-binding site, and it selectively deacetylases alpha-tubulin and Hsp90. Here, we report the discovery that the redox regulatory proteins, peroxiredoxin (Prx) I and Prx II are specific targets of HDAC6. Prx are antioxidants enzymes whose main function is H(2)O(2) reduction. Prx are elevated in many cancers and neurodegenerative diseases. The acetylated form of Prx accumulates in the absence of an active HDAC6. Acetylation of Prx increases its reducing activity, its resistance to superoxidation, and its resistance to transition to high-molecular-mass complexes. Thus, HDAC6 and Prx are targets for modulating intracellular redox status in therapeutic strategies for disorders as disparate as cancers and neurodegenerative diseases.


[Hypothyroidism and immunotherapy using interferon or interleukin for metastatic renal adenocarcinoma].
The authors report a case of hypothyroidism occurring during cytokine treatment of metastatic renal cancer. This is a relatively rare complication of immunotherapy, whose aetiopathogenesis remains unclear. Possible hypotheses include an autoimmune process or direct toxicity. Thyroid function tests at the start of immunotherapy and regular monitoring are therefore recommended during treatment with interferon and/or interleukin. If hypothyroidism is not recognised, its clinical symptoms and signs could be attributed to cytokine toxicity, leading to unwarranted discontinuation of treatment when L-thyroxin replacement therapy would have been sufficient.


Perceptions and practices of commensality and solo-eating among Korean and Japanese university students: A cross-cultural analysis.
Commensality, eating together with others, is a major representation of human sociality. In recent time, environments around commensality have changed significantly due to rapid social changes, and the decline of commensality is perceived as a serious concern in many modern societies. This study employs a cross-cultural analysis of university students in two East Asian countries, and examines cross-cultural variations of perceptions and actual practices of commensality and solo-eating. The analysis was drawn from a free-list survey and a self-administrative questionnaires of university students in urban Korea and Japan. The free-listing survey was conducted with a small cohort to explore common images and meanings of commensality and solo-eating. The self-administrative questionnaire was developed based on the result of the free-list survey, and conducted with a larger cohort to examine reasons and problems of practices and associated behaviors and food intake. We found that Korean subjects tended to show stronger associations between solo-eating and negative emotions while the Japanese subjects expressed mixed emotions towards the practice of solo-eating. In the questionnaire, more Korean students reported they prefer commensality and tend to eat more quantities when they eat commensally. In contrast, more Japanese reported that they do not have preference on commensality and there is no notable difference in food quantities when they eat commensally and alone. Compared to the general Korean cohort finding, more proportion of overweight and obese groups of Korean subjects reported that they tend to eat more when they are alone than normal and underweight groups. This difference was not found in the overweight Japanese subjects. Our study revealed cross-cultural variations of perceptions and practices of commensality and solo-eating in a non-western setting.


Metal Exchange Boosts the CO2 Selectivity of Metal Organic Frameworks Having Zn-Oxide Nodes.
A large number of metal organic frameworks (MOFs) synthesized to date have nodes with a Zn metal, and a detailed understanding of their gas separation efficiency upon metal exchange is needed to pave the way for designing the next generation of MOFs. In this work, we implemented a protocol to identify MOFs with Zn nodes out of 10,221 MOFs and classified them into two main groups. Depending on the pore properties and adsorption selectivities, two MOFs from IRMOFs and two MOFs from ZnO-MOFs were selected. The metal atom (Zn) of the selected four MOFs was exchanged with eight different metals (Cd, Co, Cr, Cu, Mn, Ni, Ti, and V), and 32 different metal-exchanged MOFs (M-MOFs) were obtained. By performing grand canonical Monte Carlo simulations, we investigated the influence of the metal type on the CO2/H2 and CO2/CH4 separation performances of these 32 M-MOFs. Physical properties of the MOFs such as the pore size and surface area, and chemical properties such as the partial charges of the atoms in the framework were investigated to understand the effect of metal exchange on the gas adsorption and separation performances of materials. Exchange of Zn with V and Cr led to a remarkable increase in the CO2 uptakes of selected MOFs and these increases were reflected on the adsorption selectivity, working capacity, and the adsorbent performance score of MOFs. The exchange of Zn with V increased the selectivity of one of the MOFs from 119 to 355 and the adsorbent performance score from 70 to 444 mol/kg, while for another MOF, exchange of Zn with Cr increased the selectivity from 161 to 921 and the adsorbent performance score from 162 to 1233 mol/kg under the condition of vacuum swing adsorption. The molecular level insights we provided to explain the improvement in the gas separation performances of M-MOFs will serve as a guide to design materials with exceptional CO2 separation performances.


Breaking the Silence: A Workshop for Medical Students on Dealing With Failure in Medicine.
Failure is a powerful teacher but an emotionally stressful experience. Before residency, when failure in clinical training is inevitable, medical students should learn to talk about and cope with failure. However, medical school curricula rarely include this topic, and physicians seldom share their mistakes and failures with trainees. This report describes and evaluates a workshop on dealing with failure in medicine. Two attending surgical consultants and a life coach facilitated the workshop between February 2021 and February 2022, which consisted of different educational approaches, such as presentations, small group discussions, and journal clubs. The sessions aimed to enable medical learners to identify and analyze actual and potential failure events in everyday clinical practice and learn from them, disclose and communicate medical failures and "speak up," reflect on failure and develop coping strategies, and understand the moderating role of fear of failure. Thirty medical students participated in the workshop. Dealing with failure in a productive manner was the medical learners' key learning objective and anticipated takeaway from the workshop. After the workshop, 19 of the 30 participants anonymously completed the standard university evaluation form. The medical students gave the workshop a mean (SD) rating of 8.59 (0.98) on a Likert scale ranging from 1 to 10. They felt better prepared to approach future challenges in a constructive manner after being equipped with strategies to deal with failure. Listening to the failure experiences of faculty and peers in a safe environment helped them accept that failure is inevitable. The findings suggest that medical students appreciated a safe environment to discuss failure. By promoting a safe learning environment early in the medical career, medical schools could make an important contribution to reducing the stigma of failure and eliminating the shame and blame culture, thus contributing to students' well-being.


MR imaging of hepatocellular carcinoma arising in genetic hemochromatosis.
A case of a 51-year-old male with previously unsuspected genetic hemochromatosis (GH) associated with hepatocellular carcinoma (HCC), for which MR imaging was useful in diagnosis, is presented. Contrast-enhanced ultrasonography depicted a mass in segment 8 of the liver and a liver tumor was suspected. The mass could not be revealed on unenhanced or enhanced CT examination. MR imaging with unenhanced T1-weighted FLASH and T2-weighted gradient echo sequences clearly depicted the tumor; the tumor appeared hyperintense against a background of low hepatic signal intensity caused by iron overload. The iron-overloaded liver provided a natural source of paramagnetic contrast for detection of HCC. Studies are required to further assess the accuracy of these sequences in detection of HCC in patients with GH.


[Dihydromyricetin reverses Herceptin resistance by up-regulating miR-98-5p and inhibiting IGF1R/HER2 dimer formation in SKBR3 cells].
To explore the effect of dihydromyricetin on the expression of miR-98-5p and its mechanism in the development of Herceptin resistance in SKBR3 cells. The expression of IGF2 and miR-98-5p and their interaction relationship were analyzed by bioinformatics analysis through TargetScan online databases. SKBR3 cells and drug-resistant SKBR3-R cells were cultured in cell experiments. Xenograft tumor mice were constructed by SKBR3 and SKBR3-R cells. Proteins were detected by western blotting and immunohistochemistry. Transfected cells were constructed by shRNA lentivirus vectors. RT-QPCR was used to detect RNA. Cell proliferation was detected by MTS method. Cell jnvasion was detected by Transwell assay. Luciferase reporting assays were used to verify RNA interactions. IGF-1R/HER2 heterodimer was determined by immunocoprecipitation. The expression of IGF2, p-IGF1R, p-Akt and p-S6K in SKBR3-R cells were significantly higher than those in SKBR3 cells, while the expression of PTEN protein was lower in SKBR3-R cells (P < 0.05). IGF1R/HER2 heterodimer in SKBR3-R cells was significantly increased (P < 0.01).The expression of IGF2 and invasion ability were significantly reduced while transfected with miR-98-5p in SKBR3-R cells (P < 0.05), but the IGF2 mRNA were no difference in both cells (P > 0.05). The expression of miR-98-5p was up-regulated and IGF2 was decreased in drug-resistant xenograft tumor mice after feeding with dihydromyricetin, and the tumor became more sensitivity to Herceptin (P < 0.05). Dihydromyricetin could induce the expression of miR-98-5p, which binds to IGF2 mRNA to reduce IGF2 expression, inhibit the IGF-1R/HER2 formation, thereby reversing cell resistance to Herceptin in SKBR3-R cells.


Do dental implants preserve and maintain alveolar bone?
Dental implants have been touted as capable of playing an active role in the maintenance of alveolar bone height, despite the lack of a sound biological basis to support this proposition. This paper reviews the biology of bone loss, the literature concerning alveolar bone remodeling in both the postextraction period and long term, and discusses the literature regarding the influence dental implant placement has on this process. Based on current evidence, implants do not have an active role in the preservation and maintenance of alveolar bone height. Following extraction of a tooth, no external influence has been identified that will prevent loss of bundle bone or alveolar bone remodeling. Additionally, the magnitude of change is patient, site, and time dependant. Further supporting evidence is required before it can be concluded that dental implants are capable of influencing alveolar bone remodeling.


Conservative approach versus urgent appendectomy in surgical management of acute appendicitis with abscess or phlegmon.
Surgical management of acute appendicitis with appendiceal abscess or phlegmon remains controversial. We studied the results of initial conservative treatment (antibiotics and percutaneous drainage if necessary, with or without interval appendectomy) compared with immediate surgery. We undertook an observational, retrospective cohort study of patients with a clinical and radiological diagnosis of acute appendicitis with an abscess or phlegmon, treated in our hospital between January 1997 and March 2009. Patients younger than 14, with severe sepsis or with diffuse peritonitis were excluded. A study group of 15 patients with acute appendicitis complicated with an abscess or phlegmon underwent conservative treatment. A control group was composed of the other patients, who all underwent urgent appendectomy, matched for age and later randomized 1:1. The infectious risk stratification was established with the National Nosocomial Infections Surveillance System (NNIS) index. Dependent variables were hospital stay and surgical site infection. Analysis was with SPSS, with p < 0.05 considered significant. Interval appendectomy was performed in 7 study group patients. Surgical site infection episodes were more frequent in the control group (6 vs. 0, p < 0.001). A greater percentage of high risk patients (NNIS ≥ 2) was identified in the control group (80 vs. 28.7%, p < 0.03), mostly related with contaminated or dirty procedures in this group (p < 0.001). No significant difference between groups was found in hospital stay. Initial conservative treatment should be considered the best therapeutic choice for acute appendicitis with abscess or phlegmon.


Nasendoscopic Findings of Velopharyngeal Sphincter in Operated Cleft Palate Patients: Is It Different than Normal Population.
Objective This study was aimed for nasendoscopic assessment of velopharyngeal sphinteric closure in patients with operated cleft palate and to compare it with normal population. Design A cross-sectional study was done in a tertiary cleft care center in 30 patients with operated cleft palate after a minimum of 6 months of their surgery and 30 randomly selected volunteers with normal speech. Both groups were one-time evaluated by three observers using 70 degree rigid nasendoscope and/or pediatric fiber optic endoscope. Velopharyngeal sphincter closure characteristics in terms of pattern of closure, dominant element involved in the closure, degree of palatal movement, and completeness of the closure were evaluated, recorded, and compared between the groups. Results In both groups, the most common pattern of closure is coronal and soft palate is the dominant mobile element in velopharyngeal closure. All normal subjects showed complete closure of the sphincter with good soft palate movement. But only 50% of the operated patients with cleft showed complete closure and even less than them had good movements of the soft palate. Conclusions Although the pattern of the closure in the operated patients is similar to the normal subjects, the movement of the soft palate and completeness of the velopharyngeal sphincter closure still remain the problem in the operated palate patients.


Urinary incontinence related to perineal muscle strength in the first trimester of pregnancy: cross-sectional study.
Objective To analyze pelvic floor muscle strength (PFMS), urinary continence and quality of life related to urinary incontinence (UI) of women in the first trimester of pregnancy. Method Cross-sectional study with a sample of 500 women who started prenatal care in a complementary healthcare facility in Guarulhos, state of São Paulo, from 2012 and 2013. Pelvic floor muscle strength was evaluated through perineometry. The pregnant women who presented UI answered the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Results It was found that maternal age (OR=1.06; CI95% 1.02-1.11) and prior UI (OR=15.12; 95%CI 8.19-27.92) are the variables that, in tandem, best explain the occurrence of UI at the beginning of pregnancy. The mean score on the ICIQ-SF was 8.2 (SD=3.9), considered a moderate impact on quality of life. Conclusion Older pregnant women with prior UI are more likely to have UI in the first trimester of pregnancy.


Spin-Conserved and Spin-Flip Optical Excitations from the Bethe-Salpeter Equation Formalism.
Like adiabatic time-dependent density-functional theory (TD-DFT), the Bethe-Salpeter equation (BSE) formalism of many-body perturbation theory, in its static approximation, is "blind" to double (and higher) excitations, which are ubiquitous, for example, in conjugated molecules like polyenes. Here, we apply the spin-flip ansatz (which considers the lowest triplet state as the reference configuration instead of the singlet ground state) to the BSE formalism in order to access, in particular, double excitations. The present scheme is based on a spin-unrestricted version of the GW approximation employed to compute the charged excitations and screened Coulomb potential required for the BSE calculations. Dynamical corrections to the static BSE optical excitations are taken into account via an unrestricted generalization of our recently developed (renormalized) perturbative treatment. The performance of the present spin-flip BSE formalism is illustrated by computing excited-state energies of the beryllium atom, the hydrogen molecule at various bond lengths, and cyclobutadiene in its rectangular and square-planar geometries.


Participant Selection from the General Japanese Population for Pulmonary Function Tests Using a Questionnaire on Symptoms and Smoking Habits During Annual Health Checkups: The Yamagata-Takahata Study.
Objective Pulmonary function tests are essential for diagnosing respiratory diseases, such as chronic obstructive pulmonary disease (COPD), but are typically not performed in Japan during annual health checkups, which hinders the early diagnosis of respiratory diseases. Methods Individuals who agreed to participate in the Yamagata-Takahata study during medical checkups in Takahata (Yamagata Prefecture, Japan) in 2011 were examined. We interviewed 669 participants (49.0% men; mean age, 67.7 years old) regarding their respiratory symptoms and smoking habits and performed pulmonary function tests during the study. Results Based on pulmonary function test results, 141 participants had pulmonary dysfunction, and 115 had obstructive pulmonary dysfunction. The risk of respiratory dysfunction, particularly obstructive respiratory dysfunction, was examined by referring to a questionnaire tool for an early COPD diagnosis. The associations between age, the smoking history, respiratory symptoms, and obstructive respiratory dysfunction were evaluated. Obstructive respiratory dysfunction was found in 17.6% of participants ≥50 years old and 19.5% ≥60 years old, 30.3% had a smoking history, and 32.8% had respiratory symptoms. Furthermore, the participants with multiple factors had a higher probability of obstructive respiratory dysfunction. Conclusion Subjects with obstructive pulmonary dysfunction are expected to be efficiently identified by extracting individuals by age and smoking habit and through a respiratory symptom questionnaire, although pulmonary function tests cannot be performed for all individuals during health checkups.


A Recurrent Pleomorphic Xanthoastrocytoma in the Cerebellum in a Young Adult: A Case Report and Review of the Literature.
Pleomorphic xanthoastrocytoma (PXA) is a rare glioma. It accounts for less than 1% of all astrocytomas. About 98% of PXAs originate supratentorially with the temporal lobe being the most common location. Cases of infratentorial PXAs are rarely reported in the medical literature. The tumor presents with a wide variation of symptoms based on the neuroanatomy involved with the location and size of the tumor, with seizures being the most reported symptom. The diagnosis depends on histological and clinical features along with radiologic features. We searched the keywords "Pleomorphic xanthastrocytoma, PXA, cerebellum, infratentorium, astrocytoma, gliomas" in the PubMed database; from 1979 to the current date, 28 cases were found in the medical literature featuring PXA in the infratentorium. We present the 29th case in the literature and the first in Syria. Our patient had a lesion in the right cerebellum and presented with a history of intermittent headache for 5 months followed by progressive gait disturbances and blurry vision and was misdiagnosed at the time of presentation with a high-grade glioma which is a common confusion because of the histological and clinical similarities. The patient underwent a suboccipital craniotomy, and adjuvant therapy with a combination of radiotherapy and chemotherapy with temozolomide was initiated at first. Then, the patient presented with a relapse of symptoms and went through another surgery where frozen sections suggested the diagnosis of PXA; further histopathological and immunohistochemical studies confirmed the diagnosis. Alongside highlighting the diagnostic challenge of this rare tumor, we did a brief review of the literature.


Age-related changes in the intact and sympathetically denervated gerbil pineal gland.
The pineal gland of four-month-old gerbils contains numerous calcareous deposits (corpora arenacea or concretions). Also, the tissue appears vacuolated due to the presence of a number of large rounded spaces. The deposits are usually associated with or lying within these "vacuoles". By eight months of age, the number of both the corpora arenacea and the "vacuoles" are increased over those present in the pineals of four-month-old gerbils. Bilateral superior cervical ganglionectomy at one month of age prevents the formation of both the concretions and "vacuoles". The cells in the sympathetically denervated pineal glands are smaller than those in pineal glands of animals that possess intact superior cervical ganglia.


Sibling incest: reports from forty-one survivors.
An exploratory study was conducted with a convenience sample of 41 adult survivors of sibling incest using a retrospective survey design. Participants were interviewed about their childhood sexual experiences with a sibling. Most participants reported vaginal or oral intercourse and coercive experiences. Half of the sample reported sexual experiences with family members, as well as other child abuse. Half of the participants showed evidence of distorted beliefs about child sexual abuse. Disclosure of the incest during childhood was rare. doi:10.1300/ J070v15n04_02.


Prediction of survival by pretreatment health-related quality-of-life scores in a prospective cohort of patients with head and neck squamous cell carcinoma.
To evaluate the association between pretreatment health-related quality-of-life (HRQOL) scores and survival in a heterogeneous cohort of patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC). Prospective cohort study. University hospital and referral center in Western Norway. A total of 106 patients with intact cognitive functioning who were younger than 78 years, were diagnosed as having HNSCC, and underwent treatment with curative intent from November 1, 2002, through June 30, 2005. Overall survival and HRQOL scores obtained at the time of diagnosis. All dichotomized HRQOL sum scores except the functional score (P = .20) were significantly predictive of survival in univariate analyses. The hazard ratios of the dichotomized general symptom, global quality-of-life, and head and neck sum score were 3.66, 0.31, and 2.28, respectively. All sum scores except the dichotomized functional score remained predictive of survival after sequential adjustment for sociodemographic and clinical characteristics, neuroticism, choice of psychological coping, current smoking and alcohol consumption, and comorbidities. Similar findings were found for specific HRQOL indices of physical functioning, dyspnea, sleep disturbance, appetite loss, swallowing, and social eating from the European Organization for Research and Treatment of Cancer 30-Item Core Quality of Life Questionnaire, version 3.0, and the Quality of Life-Head and Neck Cancer Module. Moreover, patients in the highest scoring quartiles for the symptom sum scores and/or the lowest scoring quartile for the global score had overall mortality rates of 50% to 64% compared with 23% to 26% among the other patients. The HRQOL sum scores and specific indices among HNSCC patients predict survival independently of established known prognostic factors.


Dietary Fiber Intake is Associated with Cognitive Function in Older Adults: Data from the National Health and Nutrition Examination Survey.
Aging is a global health challenge that is associated with a decline in cognitive function. In the United States, most older adults (≥50 years) do not meet the recommended daily fiber intake, although preliminary evidence suggests that dietary fiber consumption could elicit clinical benefits on cognitive function. We investigated the associations between dietary fiber intake and cognitive function in older adults. We analyzed data from the US National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014, with a study cohort of 1070 older adults (≥60 years). Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning Test (WLT), Word Recall Test (WRT) and their Intrusion Word Count Tests (WLT-IC and WRT-IC), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Multiple linear regression and cubic spline analyses were employed to examine the association between dietary fiber intake and cognitive performance on a test-by-test basis, after covariates adjustment (ie, age, sex, race, socioeconomic status, educational level, medical history, body mass index, alcohol, and energy intake). Participants had a mean age of 69.2 years and were primarily non-Hispanic white of middle-high socioeconomic status with a college degree at minimum. The mean dietary fiber intake was 17.3 g/d. The analysis showed that dietary fiber intake was positively associated with DSST (P = .031). No associations with CERAD WLT (P = .41), WRT (P = .68), WLT-IC (P = .07), and WRT-IC (P = .28), and AFT (P = .40) scores were observed. A plateau in DSST score was revealed at a dietary fiber intake of 34 g/d. Higher dietary fiber intake is associated with improved specific components of cognitive function in older adults aged 60 years and older. Public health interventions that target a recommended dietary fiber intake may provide a promising strategy to combat cognitive decline in high-risk groups of older adults.


Bioethics and "Rightness".
If bioethics seeks to affect what people do and don't do as they respond to the practical issues that confront them, then it is useful to take seriously people's sense of rightness. Rightness emerges from the fabric of a life-including the economy of its geography, the events of its times, its popular culture-to be what the sociologist Pierre Bourdieu calls a predisposition. It is the product of a way of life and presupposes continuing to live that way. Rightness is local and communal, holding in relationship those who share the same predisposing sense of how to experience. Rightness is an embodied way of evaluating what is known to matter and choosing among possible responses. Bioethics spends considerable time on what people should do and on the arguments that support recommended actions. It might spend more time on what shapes people's sense of the rightness of what they feel called to do.


Lack of paternal inheritance of muscle mitochondrial DNA in sporadic mitochondrial myopathies.
In 2002, paternal inheritance of muscle mitochondrial DNA (mtDNA) was reported in a patient with exercise intolerance and a mitochondrial DNA (mtDNA) mutation restricted to skeletal muscle. To evaluate whether paternal inheritance is a common phenomenon, we studied 10 sporadic patients with skeletal muscle-restricted mtDNA mutations: five harbored mtDNA point mutations in protein-coding genes and five had single mtDNA deletions. We performed haplotype analysis and direct sequencing of the hypervariable regions 1 and 2 of the D-loop in muscle and blood from the patients and, when available, in blood from their parents. We did not observe paternal inheritance in any of our patients.


Serum cholesterol levels preceding to suicide death in Japanese workers: a nested case-control study.
To investigate the association between suicide death and serum cholesterol levels as measured at times close to suicide death. We conducted a nested case-control study of 41 cases of suicide deaths and 205 matched controls with serum total cholesterol (TC) levels till 3 years before suicide death in a large cohort of Japanese workers. Individuals in the lowest versus highest tertile/predefined category of TC in a Japanese working population had a three- to four-fold greater risk of suicide death. Each 10 mg/dl decrement of average TC was associated with an 18% increased chance of suicide death (95% confidence interval, 2-35%). Similar results were found for TC levels at each year. These results suggest that a low serum TC level in recent past is associated with an increased risk of suicide death.


Prefrontal dysconnectivity links to working memory deficit in first-episode schizophrenia.
Working memory (WM) deficit is a core feature of schizophrenia and is characterized by abnormal functional integration in the prefrontal cortex, including the dorsolateral prefrontal cortex (dLPFC), dorsal anterior cingulate cortex (dACC), and ventrolateral prefrontal cortex (vLPFC). However, the specific mechanism by which the abnormal neuronal circuits that involve these brain regions contribute to this deficit is still unclear. Therefore, this study focused on these regions and sought to answer which abnormal causal relationships in these regions can be linked to impaired WM in schizophrenia. We used spectral dynamic causal modeling to estimate directed (effective) connectivity between these regions based on resting-state functional magnetic resonance imaging data from healthy control (HC) subjects and patients with first-episode schizophrenia (FES). By comparing these effective connections in the controls and patients, we found that the effective connectivity from the dACC to the dLPFC and from the right dLPFC to the left vLPFC was weaker in the FES group than in the HC group. Furthermore, these effective connections displayed a positive correlation with WM performance in the HCs. However, in the FES patients, the effective connectivity from the dACC to the dLPFC was not correlated with WM performance, and the effective connectivity from the right dLPFC to the left vLPFC was negatively correlated with WM performance. These results could be explained by an aberrant top-down mechanism of WM processing and provide new evidence for the dysconnectivity hypothesis of schizophrenia.


Revisional Single-Anastomosis Gastric Bypass for a Patient With Severe Protein-Calorie Malnutrition: A Case Report.
Obesity is a chronic disorder with numerous manifestations as well as pandemic occurrence on a global scale. One-anastomosis gastric bypass (OAGB) is a safe and effective surgical procedure for the treatment of obesity and metabolic diseases. Revision surgery may be necessary due to postoperative issues, such as protein-calorie deficiency, weight increase, or inadequate weight loss. This case describes a 40-year-old female patient who came to our service due to protein-caloric malnutrition, with a history of OAGB. The patient underwent revision surgery for OAGB reversal. One year after surgery the patient had a body mass index (BMI) of 25; today she is healthy, consumes a regular diet, and has no associated complications.


Asymmetry Factors Shaping Regular and Irregular Bursting Rhythms in Central Pattern Generators.
Central Pattern Generator (CPG) circuits are neural networks that generate rhythmic motor patterns. These circuits are typically built of half-center oscillator subcircuits with reciprocally inhibitory connections. Another common property in many CPGs is the remarkable rich spiking-bursting dynamics of their constituent cells, which balance robustness and flexibility to generate their joint coordinated rhythms. In this paper, we use conductance-based models and realistic connection topologies inspired by the crustacean pyloric CPG to address the study of asymmetry factors shaping CPG bursting rhythms. In particular, we assess the role of asymmetric maximal synaptic conductances, time constants and gap-junction connectivity to establish the regularity of half-center oscillator based CPGs. We map and characterize the synaptic parameter space that lead to regular and irregular bursting activity in these networks. The analysis indicates that asymmetric configurations display robust regular rhythms and that large regions of both regular and irregular but coordinated rhythms exist as a function of the asymmetry in the circuit. Our results show that asymmetry both in the maximal conductances and in the temporal dynamics of mutually inhibitory neurons can synergistically contribute to shape wide regimes of regular spiking-bursting activity in CPGs. Finally, we discuss how a closed-loop protocol driven by a regularity goal can be used to find and characterize regular regimes when there is not time to perform an exhaustive search, as in most experimental studies.


Ultraviolet-induced mutations in Cockayne syndrome cells are primarily caused by cyclobutane dimer photoproducts while repair of other photoproducts is normal.
We compared the contribution to mutagenesis in Cockayne syndrome (CS) cells of the major class of UV photoproducts, the cyclobutane pyrimidine dimer, to that of other DNA photoproducts by using the mutagenesis shuttle vector pZ189. Lymphoblastoid cell lines from the DNA repair-deficient disorders CS and xeroderma pigmentosum (XP) and a normal line were transfected with UV-treated pZ189. Cyclobutane dimers were selectively removed before transfection by photoreactivation (PR), leaving nondimer photoproducts intact. After UV exposure and replication in CS and XP cells, plasmid survival was abnormally reduced and mutation frequency was abnormally elevated. After PR, plasmid survival increased and mutation frequency in CS cells decreased to normal levels but remained abnormal in XP cells. Sequence analysis of > 200 mutant plasmids showed that with CS cells a major mutational hot spot was caused by unrepaired cyclobutane dimers. These data indicate that with both CS and XP cyclobutane dimers are major photoproducts generating reduced plasmid survival and increased mutation frequency. However, unlike XP, CS cells are proficient in repair of nondimer photoproducts. Since XP but not CS patients have a high frequency of UV-induced skin cancers, our data suggest that prevention of UV-induce skin cancers is associated with proficient repair of nondimer photoproducts.


[Laboratory diagnosis in tuberculosis].
The most reliable signs of tuberculosis infection is detection of M. tuberculosis complex in biological fluids and biopsy specimens from focus of lesions. The sensitivity of laboratory diagnostic methods is different for different biological materials, which dictates the utilization of a complex laboratory approach, including microscopy, bacteriological methods, detection of specific IgG, IgM, IgA, and polymerase chain reaction.


Saccharomyces cerevisiae and Torulaspora delbrueckii Intra- and Extra-Cellular Aromatic Amino Acids Metabolism.
Tryptophan, phenylalanine, and tyrosine play an important role as nitrogen sources in yeast metabolism. They regulate biomass production and fermentation rate, and their catabolites contribute to wine health benefits and sensorial character through the yeast biotransformation of grape juice constitutes into biologically active and flavor-impacting components. A UHPLC-MS/MS method was applied to monitor 37 tryptophan/phenylalanine/tyrosine yeast metabolites both in extra- and intracellular extracts produced by the fermentation of two Saccharomyces cerevisiae strains and one Torulaspora delbrueckii. The results shed light on the intra- and extra-cellular metabolomic dynamics, by combining metabolic needs, stimuli, and signals. Among others, the results indicated (a) the production of 2-aminoacetophenone by yeasts, mainly by the two Saccharomyces cerevisiae; (b) the deactivation and/or detoxification of tryptophol via sulfonation reaction; and (c) the deacetylation of N-acetyl tryptophan ethyl ester and N-acetyl tyrosine ethyl ester by producing the corresponding ethyl esters.


Large-conductance Ca(2+)-activated K(+) channel involvement in suppression of cerebral ischemia/reperfusion injury after electroacupuncture at Shuigou (GV26) acupoint in rats.
Excess activation and expression of large-conductance Ca(2+)-activated K(+) channels (BKCa channels) may be an important mechanism for delayed neuronal death after cerebral ischemia/reperfusion injury. Electroacupuncture can regulate BKCa channels after cerebral ischemia/reperfusion injury, but the precise mechanism remains unclear. In this study, we established a rat model of cerebral ischemia/reperfusion injury. Model rats received electroacupuncture of 1 mA and 2 Hz at Shuigou (GV26) for 10 minutes, once every 12 hours for a total of six times in 72 hours. We found that in cerebral ischemia/reperfusion injury rats, ischemic changes in the cerebral cortex were mitigated after electroacupuncture. Moreover, BKCa channel protein and mRNA expression were reduced in the cerebral cortex and neurological function noticeably improved. These changes did not occur after electroacupuncture at a non-acupoint (5 mm lateral to the left side of Shuigou). Thus, our findings indicate that electroacupuncture at Shuigou improves neurological function in rats following cerebral ischemia/reperfusion injury, and may be associated with down-regulation of BKCa channel protein and mRNA expression. Additionally, our results suggest that the Shuigou acupoint has functional specificity.


Optical Coherence Tomography and Glaucoma Progression: A Comparison of a Region of Interest Approach to Average Retinal Nerve Fiber Layer Thickness.
To determine whether the change in the retinal nerve fiber layer (RNFL) thickness in a region of interest (ROI) is a better measure of glaucoma progression than the change in average circumpapillary (cp) RNFL thickness. Disc cube scans were obtained with frequency domain optical coherence tomography from 60 eyes of 60 patients (age, 61.7±12.7 y) with early or suspected glaucoma and controlled intraocular pressure. The average time between 2 test dates was 3.2±1.8 years. En-face images of the scans from the 2 tests were aligned based on the blood vessels, and cp images were derived for an annulus 100 μm wide and 3.4 mm in diameter, centered on the disc. An ROI was defined as the portion of the circumpapillary retinal nerve fiber layer (cpRNFL) plot within the temporal disc that extended below the 1% confidence interval for ≥5 degrees. Trend analysis using multilevel mixed-effects models was used to compare the rates of change between ROI width and average cpRNFL thickness. In total, 26 of the 60 eyes had a total of 33 ROIs. The ROI width significantly increased between the 2 test dates (median, 4.9 degrees; Q1=1.03 degrees, Q3=10.5 degrees). In comparison, the average cpRNFL thickness did not decrease significantly over the same period (median, -0.7 μm; Q1=-2.7 μm, Q3=2.7 μm). Mixed-effects linear models confirmed significant ROI progression (P=0.015), but not average cpRNFL (P=0.878). In this population, RNFL thinning in a ROI is a better measure of progression than is average cpRNFL thickness change.


Results of total hip arthroplasty for Crowe Type III developmental hip dysplasia.
From 1969 through 1980, 90 hips in 82 patients had cemented total hip arthroplasty for Type III developmental hip dysplasia. Seventy hips were reviewed at an average of 16.6 years (range, 5-23 years) after operation. Aseptic loosening developed in 53% of acetabular cups and 40% of femoral stems. Despite attempts to place acetabular components in the anatomic center, 18 cups (25.7%) were placed outside that area. Using a measurement method to determine the true acetabular region and approximate femoral head center, final acetabular loosening strongly correlated with initial cup placement. Loosening occurred in 15 of 18 cups (83.3%) initially positioned outside of the true acetabular region compared with loosening in 22 of 52 cups (42.3%) initially positioned within the true acetabular region. Acetabular loosening also correlated with initial lateral displacement or initial superior displacement of the hip center from the approximate femoral head center. Initial cup placement medial to the approximate femoral head center was predictive of successful long term acetabular component fixation. The method of acetabular reconstruction did not affect eventual cup loosening. Placement of the hip arthroplasty center of rotation in or near the true acetabular region is recommended.


Volatile nitrosamines in the main stream smoke of black tobacco.
The cigarettes studied are smoked through an automatic device. The mainstream smoke is trapped in Citrate-Phosphate buffer pH 4.5 containing 20 mM ascorbic acid. The volatile nitrosamines are extracted in dichloromethane, purified on alumina column, then analysed by gas-chromatography with a thermal energy analyzer (TEA) detector. The two main volatile nitrosamines quantified are: Nitrosodimethylamine and Nitrosopyrrolidine.


Effect of professional society recommendations on women's desire for a routine pelvic examination.
The American College of Physicians strongly recommends against performing pelvic examinations in asymptomatic, nonpregnant women, citing evidence of harm (false-positive testing, unnecessary surgery) and no evidence of benefit. In contrast, the American Congress of Obstetricians and Gynecologists recommends pelvic examinations in asymptomatic women beginning at age 21 years, citing expert opinion. We sought to evaluate if providing women with professional societies' conflicting statements about pelvic examinations (recommendations and rationales) would influence their desire for a routine examination. We recruited 452 women ages 21-65 years from 2 women's clinics to participate in a 50-minute face-to-face interview about cervical cancer screening that included a 2-phase study related to pelvic examinations. In the first phase, 262 women were asked about their desire for the examination without being provided information about professional societies' recommendations. In the second phase, 190 women were randomized to review summaries of the American College of Physicians or American Congress of Obstetricians and Gynecologists statement followed by an interview. First-phase participants served as the referent: 79% (208/262) indicated they would want a routine examination if given a choice. In the second phase, a similar percentage of women randomized to the American Congress of Obstetricians and Gynecologists summary had this desire (82%: 80/97; adjusted odds ratio, 1.37; 95% confidence interval, 0.69-2.70). Women randomized to the American College of Physicians summary, however, were less likely to indicate they would opt for an examination (39%: 36/93; adjusted odds ratio, 0.12; 95% confidence interval, 0.06-0.21). Overall, 94% (179/190) believed the potential benefits and harms should be discussed prior to the examination. Providing women with a professional society's recommendation advising against routine pelvic examinations substantially reduced their desire to have one. Educational materials are needed to ensure women's informed preferences and values are reflected in decisions about pelvic examinations.


Intra- vs intersubunit communication in the homodimeric restriction enzyme EcoRV: Thr 37 and Lys 38 involved in indirect readout are only important for the catalytic activity of their own subunit.
EcoRV is a dimer of two identical subunits which together form one binding site for the double-stranded DNA substrate. Concerted cleavage of both strands of the duplex requires intersubunit communication to synchronize the two catalytic centers of EcoRV. Here we address the question of how contacts to the DNA backbone trigger conformational changes which lead to the activation of both catalytic centers. The structure of the specific EcoRV-DNA complex shows that a region including amino acids Thr 37 and Lys 38 is involved in interactions with the DNA backbone and is a candidate for intersubunit communication. Homodimeric EcoRV T37A and K38A variants have a 1000-fold reduced catalytic activity. To examine whether Thr 37 and Lys 38 of one subunit affect the catalytic center in the same subunit and/or in the other subunit, we have produced heterodimeric variants containing a Thr 37 --> Ala or Lys 38 --> Ala substitution in one subunit combined with a wild type (wt) subunit (wt/T37A and wt/K38A) or with a subunit which contains an amino acid substitution (Asp 90 --> Ala) in the active site (D90A/T37A and D90A/K38A). Cleavage experiments with supercoiled pAT153 show that wt/T37A and wt/K38A preferentially nick the DNA. A steady-state kinetic analysis of the cleavage of an oligodeoxynucleotide substrate shows that the activity of wt/T37A and wt/K38A is half of that of wild type EcoRV, whereas D90A/T37A and D90A/K38A are almost inactive. These results demonstrate that Thr 37 and Lys 38 affect primarily the catalytic center in their own subunit and that both subunits of EcoRV can be activated independently of each other. We suggest that Thr 37 and Lys 38 control the catalytic activity of the active site in their own subunit by positioning alpha-helix B.


Mobilome-driven partitions of the resistome in Salmonella.
Mobile genetic elements (MGEs) or mobilomes promote the mobilization and dissemination of antimicrobial resistance genes (ARGs), serving as critical drivers for antimicrobial resistance (AMR) accumulation, interaction, and persistence. However, systematic and quantitative evaluations of the role of mobilome in spreading resistome in a bacterial pathogen remain unaddressed, partially due to the lack of closed genomes. Here, we examined MGEs across 1,817 Salmonella isolates with complete genomic sequences from 58 countries between 1911 and 2022. We found the plasmid harboring 69.8% ARGs to be the largest ARG reservoir, correlated with serovar-based evolution in most Salmonella lineages. Prophages, specifically RCS47 and SJ46, play a crucial role in the plasmids' plasticity and the acquisition of ARGs. Furthermore, distinct ARG accumulation, including resistance toward last-resort antibiotics, exhibited an MGE-favored manner. Certain socioeconomic and ecological factors, as additional layers of mediators, are associated with the preferential distribution of MGE-mediated ARGs in Salmonella. Collectively, this study demonstrated an uncharted knowledge of the segmentation of Salmonella resistome driven by mobilome, elucidating dynamic drivers and distinct mediators for resistome development that are of immediate relevance for targeted interventions. IMPORTANCE Antimicrobial resistance (AMR) has become a significant global challenge, with an estimated 10 million deaths annually by 2050. The emergence of AMR is mainly attributed to mobile genetic elements (MGEs or mobilomes), which accelerate wide dissemination among pathogens. The interaction between mobilomes and AMR genes (or resistomes) in Salmonella, a primary cause of diarrheal diseases that results in over 90 million cases annually, remains poorly understood. The available fragmented or incomplete genomes remain a significant limitation in investigating the relationship between AMR and MGEs. Here, we collected the most extensive closed Salmonella genomes (n = 1,817) from various sources across 58 countries. Notably, our results demonstrate that resistome transmission between Salmonella lineages follows a specific pattern of MGEs and is influenced by external drivers, including certain socioeconomic factors. Therefore, targeted interventions are urgently needed to mitigate the catastrophic consequences of Salmonella AMR.


[Comparative Study on Efficiency of Extraction of Boiling Powder and Traditional Herbal PiecesⅠ. Part of Root and Rhizome,Flower,Leaf and Whole Plant Medicinal Materials].
To compare the efficiency of extraction of boiling powder and traditional herbal pieces of root and rhizome, flower, leaf and whole plant medicinal materials for providing a reference for the study and clinical application of boiling powder. 19 kinds of root and rhizome herbs, the 4 kinds of flower medicinal materials, the 2 kinds of leaf medicinal materials and the 2 kinds of whole plant medicinal materials were chosen as the researh object and were crushed into boiling powder. The contents of the active ingredients and dry extract rate in the water decoction were set as the index to compare the extraction efficiency of boiling powder and traditional herbal pieces. Boiling powder was added ten times of water, decocted one time, decoction time was only ten min, the dry extract rate and the concentration of ingredients in the decoction of boiling powder were not less than those in the traditional decoction of herbal pieces( ten times of water, decoction time was 50 min),this difference was mainly caused by the different of texture density and size of the medicinal materials. The boiling powder can not only save time and facilitate the patient, but also save a lot of medicinal materials from the perspective of chemical medicine, which is beneficial to the sustainable development of medicinal material resources.


Hypertrophic cardiomyopathy with apical left ventricular aneurysm.
We report a case of hypertrophic cardiomyopathy (HCM) with apical left ventricular aneurysm, which is difficult to review because cases are so rare. A 54-year-old Japanese man was first found to have an electrocardiographic abnormality (T-wave inversion at rest) 19 years ago, and non-obstructive apical HCM without identifiable cause was diagnosed by echocardiography, left ventriculography, and clinical findings. After 19 years, he was admitted because of repeated episodes of palpitation and chest oppression at rest. Widespread left ventricular hypertrophy from the anteroseptal wall to the apex with an apical left ventricular aneurysm was detected by echocardiography, left ventriculography, and cardiac magnetic resonance imaging. Histologic examination of the hypertrophic apical myocardium surrounding the aneurysm showed that the myocardial tissue had been extensively replaced by fibrous tissue containing hypertrophic myocardial fibers, and uptakes of [123I]-metaiodobenzyl guanidine (MIBG) and [123I-] beta-methyliodophenyl pentadecanoic acid (BMIPP) in single-photon emission photography images were reduced despite high myocardial perfusion. On the other hand, histologic examination of the hypertrophic anterior wall revealed myocardial hypertrophy with disorganization; myocardial perfusion and the uptakes of MIBG and BMIPP were preserved. Abnormalities of myocardial fatty acid metabolism and sympathetic neuron activity with preserved perfusion flow and histologic changes such as fibrosis in the apical wall are indicative of apical myocardial injury or ischemia (infarction) without coronary artery stenosis; apical aneurysm may have occurred in severe apical HCM with cavity obliteration up to the midventricular level.


The phytoestrogen ginsensoside Re activates potassium channels of vascular smooth muscle cells through PI3K/Akt and nitric oxide pathways.
In vascular smooth muscle cells, large-conductance Ca(2+)-activated K(+) channels (K(Ca) channels) play a pivotal role in determining membrane potential, and thereby the vascular tone. Ginsenoside Re, a phytochemical from ginseng, is reported to activate this channel, but its precise mechanism is unsolved. Patch clamp studies showed that ginsenoside Re activates K(Ca) channels in the arterial smooth muscle cell line A10 in a dose-dependent manner. The channel-opening effect of ginsenoside Re was inhibited by 1 microM L-NIO, an inhibitor of eNOS, but not by 3 microM SMTC, an inhibitor of nNOS, indicating that ginsenoside Re activated K(Ca) channels through activation of eNOS. SH-6 (10 microM), an Akt inhibitor, and wortmannin, a PI3-kinase inhibitor, completely blocked activation of K(Ca) channels by ginsenoside Re, indicating that it activates eNOS via a c-Src/PI3-kinase/Akt-dependent mechanism. In addition, the ginsenoside Re-induced activation of eNOS and K(Ca) channel was blocked by 10 microM ICI 182, 780, an inhibitor of membrane estrogen receptor-alpha, suggesting that eNOS activation occurs via a non-genomic pathway of this receptor. In conclusion, ginsenoside Re releases NO via a membrane sex steroid receptors, resulting in K(Ca) channel activation in vascular smooth muscle cells, promoting vasodilation and preventing severe arterial contraction.


Characterization of the bacterial microbiota across the different intestinal segments of the Qinghai semi-fine wool sheep on the Qinghai-Tibetan Plateau.
The intestinal microbiota enhances nutrient absorption in the host and thus promotes heath. Qinghai semi-fine wool sheep is an important livestock raised in the Qinghai-Tibetan Plateau; however, little is known about the bacterial microbiota of its intestinal tract. The aim of this study was to detect the microbial characterization in the intestinal tract of the Qinghai semi-fine wool sheep. The bacterial profiles of the six different intestinal segments (duodenum, jejunum, ileum, cecum, colon and rectum) of Qinghai semi-fine wool sheep were studied using 16S rRNA V3-V4 hypervariable amplicon sequencing. A total of 2,623,323 effective sequences were obtained, and 441 OTUs shared all six intestinal segments. The bacterial diversity was significantly different among the different intestinal segments, and the large intestine exhibited higher bacterial diversity than the small intestine. Firmicutes, Bacteroidetes, and Patescibacteria were the dominant phyla in these bacterial communities. Additionally, at the genus level, Prevotella_1, Candidatus_ Saccharimonas, and Ruminococcaceae_UCG-005 were the most predominant genus in duodenal segment, jejunal and ileal segments, and cecal, colonic, and rectal segments, respectively. We predicted that the microbial functions and the relative abundance of the genes involved in carbohydrate metabolism were overrepresented in the intestinal segments of Qinghai semi-fine wool sheep. The bacterial communities and functions differed among different intestinal segments. Our study is the first to provide insights into the composition and biological functions of the intestinal microbiota of Qinghai semi-fine wool sheep. Our results also provide useful information for the nutritional regulation and production development in Qinghai semi-fine wool sheep.


[Focal epiretinal fibroplasias overlying photocoagulations in diabetic retinopathy (author's transl)].
This clinico-pathological study compares photocoagulated diabetic retinae with cases of spontaneous epiretinal fibroplasia. Focal epiretinal fibroplasias were found overlying 5-10% of the Xenon-arc photocoagulations but not over Ruby-laser coagulations. These foci are contiguous-forming membranes but they do not cause surface wrinkling. The topography and appearance of the fibrous components of these membranes in trypsin-digest specimens are described and compared with foci of spontaneous epiretinal surface wrinkling. Destruction of the inner retinal surface by heavy coagulation is believed to be the principal cause of focal post-photocoagulation fibroplasia. Other possible pathogenetic factors are discussed.


Epitaxial Growth and Integration of Insulating Metal-Organic Frameworks in Electrochemistry.
With tunable pore size and rich active metal centers, metal-organic frameworks (MOFs) have been regarded as the one of the promising materials for catalysis. Prospectively, employing MOFs in electrochemistry would notably broaden the scope of electrocatalysis. However, this application is largely hindered by MOFs' conventionally poor electrical conductivity. Integrating MOFs without compromising their crystalline superiority holds a grand challenge to unveil their pristine electrocatalytic properties. In this work, we introduce an epitaxial growth strategy to accomplish the efficient integration of the insulating MOFs into electrochemistry. Particularly, with pristine-graphene-templated growth, the two-dimensional (2D) single-crystal MOF possesses a large lateral size of ∼23 μm and high aspect ratio up to ∼1500 and exhibits a significant electrochemical enhancement, with a charge transfer resistance of ∼200 ohm and a 30 mA cm-2 current density at only 0.53 V versus a reversible hydrogen electrode. The epitaxial strategy could be further applied to other 2D substrates, such as MoS2. This MOF/graphene 2D architecture sheds light on integrating insulating MOFs into electrochemical applications.


Foliar melatonin stimulates cotton boll distribution characteristics by modifying leaf sugar metabolism and antioxidant activities during drought conditions.
Drought is a severe abiotic stress affecting the plant's antioxidant system and interrupting compatible solute translocation processes, which leads to low productivity. Melatonin acts as a common growth regulator enhancing the plants defense system and regulates sugar metabolism in challenging environments. Melatonin treatments enable plants to be tolerant to abiotic stresses via enhancing their recovery potential, but its impact using various concentrations has not yet been studied in leaf physiological aspects when applied to cotton foliage during their peak flowering and boll loading stage. The overall objective of this research was to facilitate cotton boll distribution characteristics by modifying cotton leaf sugar metabolism and antioxidant activity by applying foliar melatonin (0, 25, 50, and 100 μmol l-1 ) under drought levels with a relative soil water content of 75%, 60%, and 45% ± 5 (FC1, FC2, and FC3, respectively). Higher rates of melatonin application (100 μmol l-1 ) enhanced boll distribution characteristics and controlled the boll shedding rate during drought conditions. An increase in melatonin rates proved to be more helpful in stimulating cotton sympodial leaf physiological attributes, including leaf gas exchange parameters, sugar metabolism, proline content, and antioxidants defense system as compared with less or no melatonin application during all FC conditions and showed the most significant effect at a higher melatonin concentration (M100) at 7-21 DAF. The total proline content and antioxidant activity were enhanced in the M100 treatment during all FC levels, which caused a reduction in the total malondialdehyde (MDA) contents and hydrogen peroxide (H2 O2 ) concentrations in cotton leaves. Moreover, sugar metabolism responsible genes GhSusA and SPS2 showed an upsurge in expression levels and enhanced sucrose degradation in M100 treatments during all FC levels. Furthermore, cotton boll attributes showed also a positive relation with leaf physiological and gas exchange attributes. The results suggested that foliar melatonin application during the flowering initiation stage improved the overall performance and is helpful for cotton crops productivity against drought stress.


Subungual Bowen disease in a patient with epidermodysplasia verruciformis presenting clinically as longitudinal melanonychia.
Epidermodysplasia verruciformis (EV) is a rare autosomal-recessive condition associated with a predisposition to infection with specific types of human papillomaviruses. A spectrum of wart-like lesions on the face, dorsa of the hands, and legs are characteristic clinical findings. Lesions usually develop in early childhood, persist, and may eventuate in cutaneous squamous cell carcinoma, usually in sun-exposed areas. These lesions are locally destructive and sometimes metastasize. We present a case of a 34-year-old African American woman with EV with a 9-month history of a right index finger ungual longitudinal pigmented band and nail splitting. Biopsy showed hyperkeratotic and parakeratotic subungual epithelium with verrucous hyperplasia. The superficial keratinocytes showed koilocytic changes. In addition, there was extensive, focally full-thickness keratinocyte dysmaturation with variable nuclear atypia and numerous mitotic figures, without apparent invasion. An associated melanocytic hyperplasia (confirmed by Melan-A stain), composed of large, pigment-laden dendritic melanocytes, was present without appreciable atypia or pagetoid spread. The findings are of a squamous cell carcinoma in situ arising in association with EV with incidental melanocytic hyperplasia. To the best of our knowledge, this is first report of a subungual presentation of this condition with associated melanonychia.


Photoactivatable Cre recombinase 3.0 for in vivo mouse applications.
Optogenetic genome engineering tools enable spatiotemporal control of gene expression and provide new insight into biological function. Here, we report the new version of genetically encoded photoactivatable (PA) Cre recombinase, PA-Cre 3.0. To improve PA-Cre technology, we compare light-dimerization tools and optimize for mammalian expression using a CAG promoter, Magnets, and 2A self-cleaving peptide. To prevent background recombination caused by the high sequence similarity in the dimerization domains, we modify the codons for mouse gene targeting and viral production. Overall, these modifications significantly reduce dark leak activity and improve blue-light induction developing our new version, PA-Cre 3.0. As a resource, we have generated and validated AAV-PA-Cre 3.0 as well as two mouse lines that can conditionally express PA-Cre 3.0. Together these new tools will facilitate further biological and biomedical research.


Orally bioavailable isothioureas block function of the chemokine receptor CXCR4 in vitro and in vivo.
The interaction of the chemokine receptor CXCR4 with its ligand CXCL12 is involved in many biological processes such as hematopoesis, migration of immune cells, as well as in cancer metastasis. CXCR4 also mediates the infection of T-cells with X4-tropic HIV functioning as a coreceptor for the viral envelope protein gp120. Here, we describe highly potent, selective CXCR4 inhibitors that block CXCR4/CXCL12 interactions in vitro and in vivo as well as the infection of target cells by X4-tropic HIV.


MicroRNAs in Tumor Endothelial Cells: Regulation, Function and Therapeutic Applications.
Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating evidence has shown that small single-stranded non-coding microRNAs (miRNAs) act as powerful endogenous regulators of TEC function and blood vessel formation. This systematic review provides an up-to-date overview of these endothelial miRNAs. Their expression is mainly regulated by hypoxia, pro-angiogenic factors, gap junctions and extracellular vesicles, as well as long non-coding RNAs and circular RNAs. In preclinical studies, they have been shown to modulate diverse fundamental angiogenesis-related signaling pathways and proteins, including the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway; the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; the phosphoinositide 3-kinase (PI3K)/AKT pathway; and the transforming growth factor (TGF)-β/TGF-β receptor (TGFBR) pathway, as well as krüppel-like factors (KLFs), suppressor of cytokine signaling (SOCS) and metalloproteinases (MMPs). Accordingly, endothelial miRNAs represent promising targets for future anti-angiogenic cancer therapy. To achieve this, it will be necessary to further unravel the regulatory and functional networks of endothelial miRNAs and to develop safe and efficient TEC-specific miRNA delivery technologies.


Total syntheses of ainsliadimer B and gochnatiolides a and B.
Oh my goch: The total syntheses of ainsliadimer B and gochnatiolides A and B from α-santonin have been accomplished in 25 steps with approximately 1 % overall yield. A Diels-Alder reaction of natural dehydrozaluzanin C with a monomeric guaianolide derivative allows stereoselective assembly of a dimeric gochnatiolide-type skeleton with the required stereochemistry and preinstalled functionalities for the synthesis of dimeric ainsliadimer B and gochnatiolides A and B (see scheme).


Relationship between Obsessive Beliefs and Symptoms in Patients with Obsessive Compulsive Disorder.
Misinterpretation of intrusive thoughts because of obsessive beliefs has been thought to be important in the development of obsessive compulsive symptoms. In current study, (I) the difference between OCD patients and healthy controls in regard of obsessive beliefs and (II) the relation of obsesive beliefs with the prevelance and severity of obsessive compulsive symptoms was investigated. The current study included 47 OCD patients and 44 healthy controls who have same properties with regard to age, sex and duration of education. All subjects were applied to Obsessive Beliefs Scale, Maudsley Obsessive Compulsive Scale, Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale. OCD patients were applied to Yale Brown Obsessive Compulsive Scale as well as the other scales. In analyses by controlling depression and anxiety scores, OCD patients had significantly higher scores than controls, with regard to all subscales of Obsessive Beliefs Scale. Also, prevalence of obsessive compulsive symptoms other than cleaning were correlated with obsessive beliefs about "responsibility and threat estimation" and "perfectionism and need for certainty". Hovewer, there was no correlation in between severity of obsessive compulsive symptoms and subscale scores of Obsessive Beliefs Scale. Excluding the effects of depression and anxiety, generally the results suggests that obsessive beliefs have an important role for development of obsessive compulsive symptoms. Future studies of seperated OCD subgroup with regard to obsessive compulsive symptoms will be helpful in determinig the difference among these subgroups in regard of obsessive beliefs.