The Role of Semaphorin 3A in Bone Remodeling.
Bone remodeling occurs at the bone surface throughout adult life and associates bony quantity and quality. This process is a balance between the osteoblastic bone formation and osteoclastic bone resorption, which cross-talks together. Semaphorin 3A is a membrane-associated secreted protein and regarded as a diffusible axonal chemorepellent, which has been identified in the involvement of bone resorption and formation synchronously. However, the role of Semaphorin 3A in bone homeostasis and diseases remains elusive, in particular the association to osteoblasts and osteoclasts. In this review article, we summarize recent progress of Semaphorin 3A in the bone mass, homeostasis, and diseases and discuss the novel application of nerve-based bone regeneration. This will facilitate the understanding of Semaphorin 3A in skeletal biology and shed new light on the modulation and potential treatment in the bone disorders.


Trend of circulating CD34+ cells in patients with myelofibrosis: Association with spleen response during ruxolitinib treatment.
We evaluated CD34+ cells in a single-centre series of 49 consecutive patients with myelofibrosis (MF) at baseline and during ruxolitinib therapy and examined any association with spleen response. The median (range) absolute number of circulating CD34+ cells was 0.0835 (0.001-1.528) × 109 /L at diagnosis, and 0.123 (0.002-1.528) × 109 /L at ruxolitinib start. With the exception of a transient increase after 3 months of ruxolitinib therapy, a progressive reduction in CD34+ cells count was documented, down to a minimum of 0.063 × 109 /L after 36 months. We then assessed the association between spleen diameter expressed as the distance from the left costal margin (outcome) and log(CD34+ ) cells count using random-intercept and random slope multivariable regression models to take into account within subject correlation: after adjusting for time and ruxolitinib dosage, we estimated a 0.7 cm increase (95% confidence interval 0.2-1.2, p = 0.003) in spleen length for each unit increase in log(CD34+ ) cells count (× 109 /L). Although our study has some limitations, mainly related to its retrospective design, our approach may introduce a reproducible and simple tool that could facilitate the assessment of spleen response more objectively in patients with MF treated with ruxolitinib.


[DRG's and cost/efficacy indicators in nephrology and dialysis. Results at a hospital division].
The Diagnosis Related Groups (DRGs) classification system correlates hospital performance with their relative costs and encourages more efficient productive processes. We report the following parameters: a) the distribution of hospital discharges according to the Major Diagnostic Categories (MDCs) and DRGs; b) the relationship between mean length of stay and threshold values; c) economic analysis of the cost-reimbursement pay-off. The results showed that 71.3% of DRGs belonged to nephro-urological MDC 11 and 28.7% in other internal MDCs (mainly involving cardiac and respiratory system). Of the latter, 67.7% were utilized for dialysis and transplant patients and kidney donors. In MDC 11 the most common DRGs were: the surgical DRG 315, produced by the vascular accesses for hemodialysis and by insertion of Tenckoff catheter for peritoneal dialysis, DRG 316 by cases of acute and chronic renal failure, DRG 332 by biopsy-proven glomerulonephritides. The length of stay was most commonly within range of one-third of threshold value for specific DRG; there was a low percentage of one-day stays and outlier cases. The economic analysis demonstrated that mean daily reimbursement sum was 590,714 ITL. Analysis of the overall costs yielded a mean daily cost of 455,838 ITL. In conclusion, quality indicators show that, appropriately, our specialist activity is largely devoted to the diagnosis and treatment of acute and chronic nephropathies and complications following dialysis and renal transplant.


Acute phlegmonous gastritis.
A fatal case of acute phlegmonous gastritis in a 30 year old man is reported. It was caused by Group A Streptococcus (M type 1, T type 1). Although extremely rare, clinicians need to be aware of this condition as, without intervention, it is rapidly fatal. The recommended treatment is antibiotics combined with surgical resection.


Do clinical psychologists have a role in clients' use of psychotropic medication? A mixed methods investigation exploring current forms of involvement.
This study aimed to explore whether clinical psychologists in the United Kingdom (UK) have a role with their clients' psychotropic medication by exploring forms of involvement undertaken, and decision-making behind involvement. A mixed methods design was employed; 147 clinical psychologists took part in an online survey, and 11 respondents were interviewed, selected using intensity sampling. Descriptive statistics and thematic analysis were used to analyse the quantitative and qualitative data, respectively. All respondents reported having some role with their clients' psychotropic medication. A thematic map diagram was created to capture the process of how clinical psychologists choose to become involved. Consensus was reached in that clinical psychologists do have a role with their clients' psychotropic medication, although this varies by clinician and takes on many forms. In the light of the changing role, professional guidance would help to promote clarity and consistency. Clinical psychologists are regularly engaging in roles in relation to their clients' psychotropic medication use despite little guidance or training. Findings identify a range of specific roles in relation to psychotropic medication that psychologists can take including formulating the impact of psychotropic medication, supplying information to support informed consent and withdrawal, and questioning and challenging use of psychotropic medication with colleagues and prescribers. There is a need for further research and consideration around roles given movements towards prescribing rights for psychologists (by the British Psychological Society) and recent guidance published for psychological therapists on enabling conversations with clients withdrawing from or taking psychiatric drugs (Guy et al., 2019, Guidance for psychological therapists: Enabling conversations with clients taking or withdrawing from prescribed psychiatric drugs, APPG for Prescribed Drug Dependence, London, UK).


Expression of variant-specific antigen genes in African trypanosomes.
Among the large collection of antigen genes present in the Trypanosoma brucei genome, only one is usually transcribed at a time when the parasites develop in the mammalian bloodstream. The antigen gene is transcribed in a telomeric expression site, together with other genes whose function is unknown. The nature of the RNA polymerase and transcription promoter, as well as the overall organization of the transcription unit, suggests that transcription of the antigen gene is of the ribosomal type. This transcription rapidly stops when the temperature of the parasite medium is lowered, probably accounting for the gene inactivation in the procyclic form of the insect midgut. Antigen gene expression resumes in 2 steps: first, induction of specific metacyclic variants occurs in the fly salivary glands, then injection into the blood reactivates the expression site silenced at the procyclic stage. Several telomeres can act as alternative expression sites, but the mechanism for expression-site switching is unknown. In a given expression site, the specificity of the antigen gene can change following gene conversion, telomeric reciprocal recombination, or point mutation. The alternate use of these mechanisms leads to the successive appearance of a very high number of antigenic variants, as well as to rapid evolution of the antigen gene repertoire. The relative extent of homology between nontelomeric antigen genes and the expression site may condition the programming of antigenic variation late in chronic infection, as well as the generation of chimaeric antigen genes.


Intracellular phase for an extracellular bacterial pathogen: MgtC shows the way.
Pseudomonas aeruginosa is an extracellular pathogen known to impair host phagocytic functions. However, our recent results identify MgtC as a novel actor in P. aeruginosa virulence, which plays a role in an intramacrophage phase of this pathogen. In agreement with its intracellular function, P. aeruginosamgtC gene expression is strongly induced when the bacteria reside within macrophages. MgtC was previously known as a horizontally-acquired virulence factor important for multiplication inside macrophages in several intracellular bacterial pathogens. MgtC thus provides a singular example of a virulence determinant that subverts macrophages both in intracellular and extracellular pathogens. Moreover, we demonstrate that P. aeruginosa MgtC is required for optimal growth in Mg2+ deprived medium, a property shared by MgtC factors from intracellular pathogens and, under Mg2+ limitation, P. aeruginosa MgtC prevents biofilm formation. We propose that MgtC has a similar function in intracellular and extracellular pathogens, which contributes to macrophage resistance and fine-tune adaptation to the host in relation to the different bacterial lifestyles. MgtC thus appears as an attractive target for antivirulence strategies and our work provides a natural peptide as MgtC antagonist, which paves the way for the development of MgtC inhibitors.


Noninvasive electrocardiographic imaging of arrhythmogenic substrates in humans.
Cardiac excitation is determined by interactions between the source of electric activation (membrane depolarization) and the load that cardiac tissue presents. This relationship is altered in pathology by remodeling processes that often create a substrate favoring the development of cardiac arrhythmias. Most studies of arrhythmia mechanisms and arrhythmogenic substrates have been conducted in animal models, which may differ in important ways from the human pathologies they are designed to represent. Electrocardiographic imaging is a noninvasive method for mapping the electric activity of the heart in humans in real-world conditions. This review summarizes results from electrocardiographic imaging studies of arrhythmogenic substrates associated with human clinical arrhythmias. Examples include heart failure, myocardial infarction scar, atrial fibrillation, and abnormal ventricular repolarization.


High-contrast electrooptic modulation of a photonic crystal nanocavity by electrical gating of graphene.
We demonstrate high-contrast electro-optic modulation of a photonic crystal nanocavity integrated with an electrically gated monolayer graphene. A silicon air-slot nanocavity provides strong overlap between the resonant optical field and graphene. Tuning the Fermi energy of the graphene layer to 0.85 eV enables strong control of its optical conductivity at telecom wavelengths, which allows modulation of cavity reflection in excess of 10 dB for a swing voltage of only 1.5 V. The cavity resonance at 1570 nm is found to undergo a shift in wavelength of nearly 2 nm, together with a 3-fold increase in quality factor. These observations enable a cavity-enhanced determination of graphene's complex optical sheet conductivity at different doping levels. Our simple device demonstrates the feasibility of high-contrast, low-power, and frequency-selective electro-optic modulators in graphene-integrated silicon photonic integrated circuits.


Maintenance and loss of heterozygosity in a thelytokous lineage of honey bees (Apis mellifera capensis).
An asexual lineage that reproduces by automictic thelytokous parthenogenesis has a problem: rapid loss of heterozygosity resulting in effective inbreeding. Thus, the circumstances under which rare asexual lineages thrive provide insights into the trade-offs that shape the evolution of alternative reproductive strategies across taxa. A socially parasitic lineage of the Cape honey bee, Apis mellifera capensis, provides an example of a thelytokous lineage that has endured for over two decades. It has been proposed that cytological adaptations slow the loss of heterozygosity in this lineage. However, we show that heterozygosity at the complementary sex determining (csd) locus is maintained via selection against homozygous diploid males that arise from recombination. Further, because zygosity is correlated across the genome, it appears that selection against diploid males reduces loss of homozygosity at other loci. Selection against homozygotes at csd results in substantial genetic load, so that if a thelytokous lineage is to endure, unusual ecological circumstances must exist in which asexuality permits such a high degree of fecundity that the genetic load can be tolerated. Without these ecological circumstances, sex will triumph over asexuality. In A. m. capensis, these conditions are provided by the parasitic interaction with its conspecific host, Apis mellifera scutellata.


[Estrogen-progestin contraception. Disadvantages of estrogen reduction].
Over the past few years a number of new oral contraceptives have come into the market, with the following characteristics: reduced estrogen and progestin levels in order to reduce the incidence of cardiovascular disease, triphasic pills with maximum steroid concentrations coinciding with L.H. surge. These pills enable not only a reduction in progestin levels, but also in intercurrent bleeding. However, low steroid levels could lead to insufficient antigonadotropic effect with endogenous estrogenic secretion in some women. In fact, receptivity of targeted organs to sex steroids varies enormously between individuals. This partial inhibition of ovaries in some women poses problems of short and long term consequences: functional ovarian cysts; less protection than with traditional pills (50 micrograms ethinylestradiol) in terms of ovarian or endometrium cancer, benign breast disease... Only long term comparative and prospective studies, taking into account hormonal status and the degree of fertility and parity would enable the risks associated with these new contraceptives to be established. Consequently, in the light of our present knowledge, we recommend that low-dose oral contraception be avoided: when complete blockage of ovarian activity is required, in women with a history of ovarian cysts.


The epidemic of the metabolic syndrome.
The incidence of metabolic syndrome (MS) is rising worldwide. This is partly due to a significant increase in the prevalence of obesity. Observational cross-sectional studies as well as demographic health surveys from the Middle East, point out that the prevalence of obesity increases from an average of 6% in healthy children to 20% in adolescent males and to a further 32% in elderly patients. The impact of obesity on our population is expected to be considerable; especially, as it feeds into further rising in the prevalence of hypertension, diabetes, MS and cardiovascular disease. The prevalence of MS in nondiabetic adults in Europe was recently reported to be 15%. In the Middle East, as pointed out by pilot observational projects, is estimated to be anywhere between 15-25%. The medical system is unprepared to deal with this epidemic partly due to scanty knowledge on the clinical significance of the MS and importantly as there is a limited number of specific treatments that we can offer these patients.


DNA methylation and systemic lupus erythematosus.
Several studies have indicated the importance of DNA hypomethylation in the etiology of systemic lupus erythematosus (SLE). Different enzymes linked to the DNA methylation process have been described. The identification of all these enzymes means that cells have the capacity to modify their methylation patterns. Therefore, to obtain a deeper understanding of the role this epigenetic mechanism may have on SLE, the enzymes involved in the DNA methylation mechanism must be thoughtfully analyzed. In fact, studies of enzymes (other than DNMT1) in this autoimmune disease are still lacking. We have recently investigated the simultaneous gene expression of DNMT1, DNMT3A, DNMT3B, MBD2, and MBD4 in SLE patients. Here we review some of the studies that focus on the relationship between DNA methylation and SLE as well as we report our recent findings in this field. We suggest some alternative hypothesis that could help to understand the causes of the global DNA hypomethylation observed in the CD4+ T cells of these patients.


Excited State Kinetics of Benzo[a]pyrene Is Affected by Oxygen and DNA.
Benzo[a]pyrene is a widespread environmental pollutant and a strong carcinogen. It is important to understand its bio-toxicity and degradation mechanism. Herein, we studied the excited state dynamics of benzo[a]pyrene by using time-resolved fluorescence and transient absorption spectroscopic techniques. For the first time, it is identified that benzo[a]pyrene in its singlet excited state could react with oxygen, resulting in fluorescence quenching. Additionally, effective intersystem crossing can occur from its singlet state to the triplet state. Furthermore, the interaction between the excited benzo[a]pyrene and ct-DNA can be observed directly and charge transfer between benzo[a]pyrene and ct-DNA may be the reason. These results lay a foundation for further understanding of the carcinogenic mechanism of benzo[a]pyrene and provide insight into the photo-degradation mechanism of this molecule.


Correlated Percolation, Fractal Structures, and Scale-Invariant Distribution of Clusters in Natural Images.
Natural images are scale invariant with structures at all length scales.We formulated a geometric view of scale invariance in natural images using percolation theory, which describes the behavior of connected clusters on graphs.We map images to the percolation model by defining clusters on a binary representation for images. We show that critical percolating structures emerge in natural images and study their scaling properties by identifying fractal dimensions and exponents for the scale-invariant distributions of clusters. This formulation leads to a method for identifying clusters in images from underlying structures as a starting point for image segmentation.


Ex vivo near-infrared targeted imaging of human bladder carcinoma by ICG-anti-CD47.
The low detection rate of early-stage and small tumors remains a clinical challenge. A solution to this unmet need is urgently warranted for the accurate diagnosis and treatment of bladder cancer (BC). This study aimed to evaluate the feasibility of CD47 as a target for optical molecular imaging of human BC and conduct preliminary ex vivo imaging experiments. Using indocyanine green (ICG) and a CD47 antibody (anti-CD47), we synthesized a new targeted fluorescent probe ICG-anti-CD47. A total of 25 patients undergoing radical cystectomy were prospectively included in ex vivo imaging experiments. Following surgery, the freshly isolated bladder specimens were incubated with ICG-anti-CD47, and images were captured under white light and near-infrared (NIR) light. Standard histopathologic evaluation was performed, and findings were correlated with those of CD47-targeted NIR molecular imaging. Based on the ex vivo imaging experiments, 23 and 2 patients were pathologically diagnosed with bladder urothelial carcinoma and bladder squamous cell carcinoma, respectively. There were no adverse effects of ICG-anti-CD47 on the histological structure of the tumor and normal uroepithelium. In the NIR grayscale images, the mean fluorescence intensity of the tumor tissue was significantly higher than that of the adjacent normal background tissue, which markedly improved tumor visualization. Anti-CD47-targeted NIR molecular imaging may be a feasible and powerful strategy for the accurate diagnosis of BC. Nevertheless, larger-scale randomized trials are warranted to verify the present findings.


Quantitative measurement of piezoelectric coefficient of thin film using a scanning evanescent microwave microscope.
This article describes a new approach to quantitatively measure the piezoelectric coefficients of thin films at the microscopic level using a scanning evanescent microwave microscope. This technique can resolve 10 pm deformation caused by the piezoelectric effect and has the advantages of high scanning speed, large scanning area, submicron spatial resolution, and a simultaneous accessibility to many other related properties. Results from the test measurements on the longitudinal piezoelectric coefficient of PZT thin film agree well with those from other techniques listed in literatures.


Advances in the enzymology of glutamine synthesis.
Meister's proposal of a gamma-glutamyl-P intermediate in the glutamine synthetase reaction set the scene for understanding how the stepwise activation of the carboxyl group greatly increased its susceptibility toward nucleophilic attack and amide bond synthesis. Topics covered in this review include: the discovery of the enzymatic synthesis of glutamine; the role of glutamine synthetase in defining the thermodynamics of ATPases; early isotopic tracer studies of the synthetase reaction; the proposed intermediacy of gamma-glutamyl-phosphate; the mechanism of methionine sulfoximine inhibition; stereochemical mapping of the enzyme's active site; detection of enzyme reaction cycle intermediates; borohydride trapping of gamma-glutamyl-P; positional isotope exchanges catalyzed by glutamine synthetase; regulation of bacterial enzyme; and a brief account of how knowledge of the atomic structure of bacterial glutamine synthetase has clarified ligand binding interactions. Concluding remarks also address how the so-called "Protein Ligase Problem" may be solved by extending the catalytic versatility of carboxyl-group activating enzymes.


The Subjective Experience of Youth Psychotropic Treatment.
The psychotropic treatment of youth is increasing dramatically. This article examines child and adolescent psychopharmacological research and argues that social work practice and research must examine the complex relationships, social and psychological, in youth pharmacologic treatment. Regarding identity formation, this article explores the developmental consequences when youth adopt an illness narrative to make sense of everyday medication treatment. A conceptual framework for mapping the socio-cultural context of youth medication management is outlined. In the conclusion, youth psychotropic treatment is connected to a perplexing 'interpretive gap,' which highlights the subjective quality of medication treatment.


Cleavage of the V-ATPase associated prorenin receptor is mediated by PACE4 and is essential for growth of prostate cancer cells.
Phosphatase and tensin homolog (PTEN) mutation is common in prostate cancer during progression to metastatic and castration resistant forms. We previously reported that loss of PTEN function in prostate cancer leads to increased expression and secretion of the Prorenin Receptor (PRR) and its soluble processed form, the soluble Prorenin Receptor (sPRR). PRR is an essential factor required for proper assembly and activity of the vacuolar-ATPase (V-ATPase). The V-ATPase is a rotary proton pump required for the acidification of intracellular vesicles including endosomes and lysosomes. Acidic vesicles are involved in a wide range of cancer related pathways such as receptor mediated endocytosis, autophagy, and cell signalling. Full-length PRR is cleaved at a conserved consensus motif (R-X-X-R↓) by a member of the proprotein convertase family to generate sPRR, and a smaller C-terminal fragment, designated M8.9. It is unclear which convertase processes PRR in prostate cancer cells and how processing affects V-ATPase activity. In the current study we show that PRR is predominantly cleaved by PACE4, a proprotein convertase that has been previously implicated in prostate cancer. We further demonstrate that PTEN controls PRR processing in mouse tissue and controls PACE4 expression in prostate cancer cells. Furthermore, we demonstrate that PACE4 cleavage of PRR is needed for efficient V-ATPase activity and prostate cancer cell growth. Overall, our data highlight the importance of PACE4-mediated PRR processing in normal physiology and prostate cancer tumorigenesis.


Percolation-to-droplets transition during spinodal decomposition in polymer blends, morphology analysis.
Phase separation kinetics of the off-critical mixture of polystyrene and poly(methylphenylsiloxane) is studied by the time-resolved light scattering and optical microscopy. The results from the light scattering experiments are correlated with the images obtained by the optical microscopic observation in order to find characteristic features of the scattering intensity during the percolation-to-droplets morphology transition. At the beginning of the spinodal decomposition process only a bicontinuous network is present in the system and the light scattering intensity has only one peak. The network coarsens and at the same time small droplets appear in the system resulting in a growth of the scattering intensity at very small wave vectors. When the large network starts to break up into disjoint elongated domains a second peak in the scattering intensity appears. Finally, both peaks merge into a single peak at zero wave vector, indicating a complete transformation of elongated domains into spherical droplets of variable sizes. The comparison of the direct microscopic observations with the light scattering spectra shows that the process of breaking up of the bicontinuous network starts when the growth of the first peak, corresponding to the bicontinuous pattern, becomes very slow (essentially pinned down).


Thyrotrophin releasing hormone--5-hydroxytryptamine interactions in the brain studied using chronic immunization and chemical lesioning techniques.
This study investigates the effects of chemically lesioning 5-hydroxytryptamine (5HT) neurones and chronic passive immunization of central thyrotrophin releasing hormone (TRH) on 5HT and TRH mediated behavioural responses. 5HT lesions produced by 5,7-dihydroxytryptamine (5,7-DHT) enhanced the behavioural response produced by the 5HT receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MEODMT) while decreasing the locomotor hyperactivity observed following administration of the TRH analogue CG 3509 but having no effect on the reversal of pentobarbitone sleep-time produced by CG 3509. Chronic intracerebroventricular infusion of the purified TRH antibody markedly increased the length of pentobarbitone-induced sleep-time while enhancing the effects of CG 3509 both on locomotor activity and pentobarbitone-induced sleep. TRH antibody infusion also increased the response produced by 5-MEODMT. The results indicate that chronic passive immunization of central TRH induces changes in TRH receptor responsiveness and that there is a functional interaction between TRH and 5HT neuronal systems.


Restructured low-fat cooked ham containing liquid whey fortified with lactulose.
Current health concerns have driven consumers to request products with nutritional and physiological advantages, which can be achieved by using prebiotic ingredients. Lactulose is a prebiotic with excellent functional properties and can be easily incorporated into meat products through the addition of liquid whey. This study investigated the technological and sensorial quality of restructured cooked ham elaborated without liquid whey added (control) and with liquid whey containing different contents (0, 30, 60 and 100 g kg-1 ) of lactulose. Liquid whey did not change any technological or sensorial characteristics of the product, but the general acceptability decreased due to addition of lactulose. Samples with higher lactulose concentrations had lower moisture content, pH and refreezing loss and increased carbohydrate content. Control and whey added samples had higher lightness and lower intense color than samples with lactulose. Liquid whey additions with higher lactulose content increased hardness and chewiness of the samples. Restructured cooked hams formulated with liquid whey and 30 g kg-1 of lactulose had minimal effects on the technological properties and sensory characteristics and, due to the possible benefits conferred by the prebiotic, is a potential alternative to provide meat products with prebiotic activity. © 2017 Society of Chemical Industry.


Pathogen prevalence in Amblyomma americanum and Ixodes scapularis ticks from central Appalachian Virginia, U.S.A.
Ticks are known vectors of several viral, bacterial, and protozoal pathogens that cause disease in both humans and animals. While pathogen prevalence has been studied extensively in other portions of the United States, pathogen surveillance studies within tick populations in the central Appalachian region of Virginia is almost nonexistent. Two prominent species in this region are Ixodes scapularis (the blacklegged tick) and Amblyomma americanum (the lone star tick). In this study, we collected ticks biweekly from three habitat types (forest, urban, and pasture) across eight counties in southwest Virginia from June, 2019-November, 2020. Ixodes scapularis and A. americanum captures were screened for evidence of associated tick-borne pathogens. In this region, Borrelia burgdorferi sensu stricto (15.3% in nymphs and 37.6% in adults), Anaplasma phagocytophilum (1.9% in nymphs and 12.2% in adults), and Borrelia miyamotoi (2.97% in nymphs and 2.33% in adults) were detected in I. scapularis ticks. Aside from two previously reported Powassan-positive I. scapularis ticks from Floyd County, VA, no additional Powassan-positive ticks are reported here. No evidence of Ehrlichia chaffeensis, Heartland virus (HRTV), or Bourbon virus (BRBV) was detected in collected A. americanum. Detection and confirmation of multiple emerging tick-borne pathogens in this region raises an increased concern for public health risk, calling for heightened awareness of tick-borne pathogen transmission and increased tick surveillance in understudied areas.


Differences in Autonomy and Health-Related Quality of Life between Resilient and Non-Resilient Individuals with Mild Cognitive Impairment.
The dramatic increase in the number of older people with Mild Cognitive Impairment (MCI) entails a serious public health problem. MCI involves different degrees of dependence that has been previously related to a decrease in Health-Related Quality of Life (HRQoL), due to impairment in the performance of activities of daily living. Resilient coping, as an adaptive coping style, could reduce the associated limitations derived by the characteristic deficits of MCI, and hence improve HRQoL. The principal objective of this work was to compare the level of autonomy (measured in terms of independence in the performance of basic (ADL) and instrumental (IADL) activities of daily living), and HRQoL between resilient and non-resilient individuals with MCI. The results showed a positive relationship between resilience, autonomy, and HRQoL. Hence, resilient participants exhibited higher independence in daily living activities and better HRQoL than non-resilient individuals. Mediation analyses confirmed an indirect influence of resilience on HRQoL through the mediation effect of better performance in IADLs. These findings underline the relevance of resilience as a coping style to compensate deficits in daily living in people with MCI. The inclusion of intervention programs, oriented to the promotion of resilience coping for older adults, might increase the autonomy levels in this population, improving their HRQoL.


Pre-clinical investigations of multi-path propagation in transcranial Doppler ultrasound flow phantom.
There are various practical situations in medical applications when pre-clinical investigations must be performed using a simulation environment or test bench prior to human studies. One example is the analysis of propagation channels in Transcanial Doppler (TCD) ultrasound (US), a signal processing challenge requiring the analysis of data from US waves scattered in three dimensions (3D). When examining the effects of scatterers in such channels, it is common to use a data acquisition test bench and a Doppler flow phantom. Such medical phantoms are frequently required to verify image and signal processing systems, and are often used to support algorithm development for a wide range of imaging and blood flow assessments. In this paper we describe a TCD simulation environment for the acquisition, investigation and pre-clinical data analysis of multi-path propagation in TCD US systems. This is demonstrated by comparing the anticipated theoretical and simulation channel statistics with the measured acoustic characteristics in terms of the probability distribution and autocorrelation functions.


Commentary on Zohar's "Prospects for 'genetic therapy' -- can a person benefit from being altered?
In his paper on the effects of Prenatal Genetic Intervention (PGI) on personal identity, Noam Zohar comes to a conclusion about genetic makeup and the uses of gene therapy quite different from the one I reach in another piece in this issue. Zohar's argument rests on the contention that personal identity changes with alteration of the genome, following what I have identified as the "constitutive" view. To see that this is the pillar supporting the weight of his argument, consider the following. Questions of identity aside, how can it be that altering the genome of children suffering from Lesch-Nyhan syndrome or Tay-Sachs disease so that they now produce the enzyme that they formerly lacked does not benefit them? Clearly, if their identities were not changed, such individuals would in fact realize great benefit from PGI, since the devastating bad effects of the genetic flaw would be avoided. Such a change would certainly make the altered individuals better off, that is, it would benefit them. On this, Zohar and I do not disagree. Persistence of identity through such genetic change is the sticking point.


Morphological assessment of GABA and glutamate inputs to GnRH neurons in intact female mice using expansion microscopy.
The roles GABAergic and glutamatergic inputs in regulating the activity of the gonadotrophin-releasing hormone (GnRH) neurons at the time of the preovulatory surge remain unclear. We used expansion microscopy to compare the density of GABAergic and glutamatergic synapses on the GnRH neuron cell body and proximal dendrite in dioestrous and pro-oestrous female mice. An evaluation of all synapses immunoreactive for synaptophysin revealed that the highest density of inputs to rostral preoptic area GnRH neurons occurred within the first 45 µm of the primary dendrite (approximately 0.19 synapses µm-1 ) with relatively few synapses on the GnRH neuron soma or beyond 45 µm of the dendrite (0.05-0.08 synapses µm-1 ). Triple immunofluorescence labelling demonstrated a predominance of glutamatergic signalling with twice as many vesicular glutamate transporter 2 synapses detected compared to vesicular GABA transporter. Co-labelling with the GABAA receptor scaffold protein gephyrin and the glutamate receptor postsynaptic density marker Homer1 confirmed these observations, as well as the different spatial distribution of GABA and glutamate inputs along the dendrite. Quantitative assessments revealed no differences in synaptophysin, GABA or glutamate synapses at the proximal dendrite and soma of GnRH neurons between dioestrous and pro-oestrous mice. Taken together, these studies demonstrate that the GnRH neuron receives twice as many glutamatergic synapses compared to GABAergic synapses and that these inputs preferentially target the first 45 µm of the GnRH neuron proximal dendrite. These inputs appear to be structurally stable before the onset of pro-oestrous GnRH surge.


Two new proanthocyanidin trimers isolated from Cistus incanus L. demonstrate potent anti-inflammatory activity and selectivity to cyclooxygenase isoenzymes inhibition.
Two new proanthocyanidin trimers have been isolated from Cistus incanus herb; gallocatechin-(4α→6)-gallocatechin-(4α→8)-gallocatechin (compound 1) and epigallocatechin-3-O-gallate-(4ß→8)-epigallocatechin-3-O-gallate-(4ß→8)-gallocatechin (compound 2). The structures were determined on the basis of 1D- and 2D-NMR (HSQC, HMBC) of their peracetylated derivatives, MALDI-TOF-MS and by acid-catalysed degradation with phloroglucinol. A more abundant proanthocyanidin oligomer was also isolated, purified and its chemical constitution studied by (13)C-NMR and phloroglucinol degradation. The mean molecular weight of the polymer was estimated to be about 7 to 8 flavan-3-ol-units with a ratio of procyanidin : prodelphinidin units at 1:5, some of which are derivatised by gallic acid. Water extract and higher oligomeric proanthocyanidin fractions of C. incanus significantly inhibited TPA-induced oedema when applied topically at doses of 0.5 and 1 mg/ear in mice. Furthermore, the extracts and the pure compounds inhibited COX-1 and COX-2 activities. In addition, compound 2 exhibited an IC50 of 4.5 μM against COX-2 indicating its high selectivity towards COX-2.


Are diuretics harmful in the management of acute kidney injury?
To assess the role of diuretics in acute kidney injury (AKI) and their effectiveness in preventing AKI, achieving fluid balance, and decreasing progression to chronic kidney disease (CKD). Diuretics are associated with increased risk for AKI. The theoretical advantage of diuretic-induced preservation of renal medullary oxygenation to prevent AKI has not been proven. A higher cumulative diuretic dose during the dialysis period can cause hypotension and increase mortality in a dose-dependent manner. Data on the use of forced euvolemic diuresis to prevent AKI remains controversial. Positive fluid balance has emerged as an independent predictor of adverse outcomes. Post-AKI furosemide dose had a favorable effect on mortality due in part to the reduction of positive fluid balance. There are exciting experimental data suggesting that spironolactone may prevent AKI once an ischemic insult has occurred and thus prevent the progression to CKD. Diuretics are ineffective and even detrimental in the prevention and treatment of AKI, and neither shorten the duration of AKI, nor reduce the need for renal replacement therapy. Diuretics have an important role in volume management in AKI, but they are not recommended for the prevention of AKI. There is increased emphasis on the prevention of progression of AKI to CKD.


The Whitening, Moisturizing, Anti-aging Activities, and Skincare Evaluation of Selenium-Enriched Mung Bean Fermentation Broth.
Selenium-enriched mung bean (Se-MB) is a combination of mung bean (MB) and selenium (Se), which have a variety of potential biological activities. However, little is known about the skincare activity of Se-MB. The chemical composition of Se-MB fermentation broth (Se-MBFB) was analyzed to investigate the whitening, moisturizing, and anti-aging activities of Se-MBFB. The tyrosinase inhibition, anti-melanogenic in melanocytes (B16F10 cells), and moisturizing effect in human dermal fibroblasts (HDFs) were analyzed. Besides, the free radical scavenging activity of Se-MBFB was assessed in vitro. To verify the in vivo effects and the potential of practical applications of Se-MBFB, a clinical trial was conducted on the participants: 31 Chinese women aged 25-60 years, with no pigmentation disorder, no illness, no history of hypersensitivity reaction, and no use of skincare product on the face. The participants used an Se-MBFB masque for 15-20 min after cleaning the face. The measurement points were Week 0, 2, and 4 (W0, W2, and W4) after using the masque, and target sites were cheek and canthus. The following parameters were recorded on the target sites at each visit: melanin index, skin color, cuticle moisture content, transepidermal water loss, and crow's feet. The results demonstrated that Se-MBFB was rich in polyphenols, peptides, and γ-aminobutyric acid (GABA), displayed significant free radical scavenging and tyrosinase inhibiting activities, decreased the synthesis of melanin, and upregulated the aquaporin-3 (AQP3) expression. The test of the Se-MBFB mask showed that after 4 weeks of using the Se-MBFB facemask, the faces of the participants became whiter with reduced wrinkles and increased moisture content. Se-MB possessed the excellent whitening, moisturizing, and antioxidant efficacy, which could lay a scientific foundation for utilization and development of skincare products of Se-MB and its related industrial cosmetics products.


In vivo role of the phosphate groove of PDK1 defined by knockin mutation.
AGC kinases are mediators of signalling responses stimulated by agonists and are activated following phosphorylation at their T-loop residue by the 3-phosphoinositide-dependent protein kinase-1 (PDK1). Agonists stimulate the activation of the AGC kinases p70 ribosomal S6 kinase (S6K), p90 ribosomal S6 kinase (RSK) and serum and glucocorticoid-induced protein kinase (SGK), by inducing the phosphorylation of these enzymes at a non-catalytic regulatory site termed the hydrophobic motif. This creates a high-affinity docking site enabling PDK1 to bind and phosphorylate the T-loop of these enzymes. The site that interacts with these substrates is located on the small lobe of the catalytic domain of PDK1 and is composed of a hydrophobic groove next to a basic phosphate groove. The disruption of the hydrophobic groove ablates activation of S6K, RSK and SGK, but the role of the phosphate groove in regulating the function of PDK1 has not been explored in vivo. We generated knockin ES cells, in which both copies of the gene encoding PDK1 were altered to express a form of PDK1 that retains catalytic activity and integrity of the hydrophobic groove, but in which the phosphate groove was disrupted. The knockin ES cells were viable, mutant PDK1 was expressed at normal levels and IGF1 induced activation of protein kinase B (PKB/Akt), which is a PDK1 substrate that does not require hydrophobic motif phosphorylation to be activated. In the phosphate-groove-knockin ES cells, the activation of S6K, RSK and SGK by agonists, although markedly impaired, was not abolished. PDK1 also phosphorylates the T-loop of protein kinase C (PKC) isoforms, which stabilizes these enzymes. However, in contrast to S6K, RSK and SGK, hydrophobic motif phosphorylation of these enzymes is not thought to control their activation by PDK1. Consistent with this notion, we employed appropriate PDK1-knockin ES cells to demonstrate that the hydrophobic groove of PDK1, but not the phosphate groove, is required for the stabilization of PKC isoforms. These findings provide genetic evidence that the phosphate groove of PDK1 is required for maximal activation of isoforms of S6K, SGK and RSK, but not PKC. We also found that no live births of homozygous phosphate-groove-knockin mice are observed, indicating a key role for this regulatory motif in normal development. The knockin embryos develop to a greater extent than PDK1-knockout and hydrophobic-groove-knockin embryos, which died between E9.5-E11.5. The knockin embryos are observed until E19.5 and displayed general growth retardation and craniofacial developmental defects.


Structure and expression of mobile ETnII retroelements and their coding-competent MusD relatives in the mouse.
ETnII elements are mobile members of the repetitive early transposon family of mouse long terminal repeat (LTR) retroelements and have caused a number of mutations by inserting into genes. ETnII sequences lack retroviral genes, but the recent discovery of related MusD retroviral elements with regions similar to gag, pro, and pol suggests that MusD provides the proteins necessary for ETnII transposition in trans. For this study, we analyzed all ETnII elements in the draft sequence of the C57BL/6J genome and classified them into three subtypes (alpha, beta, and gamma) based on structural differences. We then used database searches and quantitative real-time PCR to determine the copy number and expression of ETnII and MusD elements in various mouse strains. In 7.5-day-old embryos of a mouse strain in which two mutations due to ETnII-beta insertions have been identified (SELH/Bc), we detected a three- to sixfold higher level of ETnII-beta and MusD transcripts than in control strains (C57BL/6J and LM/Bc). The increased ETnII transcription level can in part be attributed to a higher number of ETnII-beta elements, but 70% of the MusD transcripts appear to have been derived from one or a few MusD elements that are not detectable in C57BL/6J mice. This element belongs to a young MusD subgroup with intact open reading frames and identical LTRs, suggesting that the overexpressed element(s) in SELH/Bc mice might provide the proteins for the retrotransposition of ETnII and MusD elements. We also show that ETnII is expressed up to 30-fold more than MusD, which could explain why only ETnII, but not MusD, elements have been positively identified as new insertions.


Diabetes and the urologist: a growing problem.
The incidence of diabetes continues to increase dramatically; this incidence is predominantly of the type-2 form which clusters together with other comorbidities of hypertension and lipid abnormalities, to form the metabolic syndrome. These conditions will have an increasing impact on urological practice, with erectile dysfunction, hypogonadism, voiding difficulties and urinary tract infections all more common in these patients. These symptoms might be the initial presentation of previously undiagnosed diabetes and it is important to recognise this condition early to avoid later complications including end-stage renal failure.


Technological Barriers in the Use of Electrochemical Microsensors and Microbiosensors for in vivo Analysis of Neurological Relevant Substances.
In this paper is presented an overview of the technological barriers faced by the in vivo brain analysis with microelectrodes. Numerous microsensors and enzymatic microbiosensors have been developed for the real time monitoring of neurotransmitters, neuromodulators, drugs and diverse other biological relevant substances. A clear understanding of the working principle, advantages and limitations is essential for the acquisition of valid data in neurological investigations. Some of the aspects presented here refer to: microelectrode insertion and positioning related to possibilities to minimize tissue damage, spatial and temporal resolution of the measurements, actual controversies in data interpretation and sensor calibration, simultaneous detection of multiple analytes, interferences and state of the art in the development of wireless devices.


Analysis of spatial-temporal distribution and influencing factors of pulmonary tuberculosis in China, during 2008-2015.
At present, the number of people with tuberculosis in China is second only to India and ranks second in the world. Under such a severe case of tuberculosis in China, prevention and control of pulmonary tuberculosis are urgently needed. This study aimed to study the temporal and geographical relevance of the pathogenesis of pulmonary tuberculosis and the factors affecting the incidence of tuberculosis. Spatial autocorrelation model was used to study the spatial distribution characteristics of pulmonary tuberculosis from a quantitative level. The research results showed that the overall incidence of pulmonary tuberculosis (IPT) in China was low in the east, high in the west and had certain seasonal characteristics. We use Spatial Lag Model to explore influencing factors of pulmonary tuberculosis. It indicates that the IPT is high in areas with underdeveloped economics, poor social services and low average smoking ages. Additionally, the IPT is high in areas with high AIDS prevalence. Also, compared with Classical Regression Model and Spatial Error Model, our model has smaller values of Akaike information criterion and Schwarz criterion. Besides, our model has bigger values of coefficient of determination (R2) and log-likelihood (log L) than the other two models. Apart from that, it is more significant than Spatial Error Models in the spatial dependence test for the IPT.


Robotic versus laparoscopic radical surgery for pediatric congenital biliary dilatation: a comparison of surgical outcomes of a single surgeon's initial experience.
This study aimed to clarify the validity of robot-assisted surgery (RAS) for pediatric patients with congenital biliary dilatation (CBD). We retrospectively compared RAS and laparoscopic surgery (LS) for pediatric CBD performed by the same certified surgeon between 2016 and 2022. We included 6 RAS and 12 LS cases in this study. One case of RAS with laparotomy was excluded from the analysis. The patients in the two groups had comparable ages and body weights. The median surgery duration, the suture time per stitch, and the time to drain removal were 385 min, 145 s, and 5 days in the RAS group and 370 min (p = 0.28), 177 s (p = 0.03), and 6 days (p = 0.03) in the LS group, respectively. The time to create the Roux-en-Y limb was significantly longer in the RAS group. Postoperative complications occurred in one RAS case and in four LS cases. Less anastomotic time per stitch and less time to drain removal suggest that RAS may contribute to accurate suturing and fine intra-pancreatic bile duct dissection. In addition, RAS requiring large movements of forceps in a large surgical field, such as Roux-en-Y creation, is inferior to LS.


Cinacalcet treatment for secondary hyperparathyroidism in dialysis patients: an observational study in routine clinical practice.
Cinacalcet reduces intact parathyroid hormone (iPTH), Ca and P serum levels in patients with secondary hyperparathyroidism (SHPT). This Spanish, multicenter, observational, retrospective study collected data from SHPT dialysis patients 12 weeks before and up to 72 weeks after starting cinacalcet in clinical practice. Data from 428 patients with uncontrolled SHPT despite receiving standard of care (29% with baseline iPTH 501-800 pg/ml; 51% with >800 pg/ml) were collected. Percentages of patients within National Kidney Foundation Kidney Disease Outcomes Quality Initiative targets at baseline and 72 weeks were: iPTH, 0 versus 32.5% (p < 0.05); Ca, 40.1 versus 50% (p < 0.05); P, 47.7 versus 53.8% (p = 0.162). Vitamin D sterol use decreased from 53.3% at baseline to 36.7% at 72 weeks (p < 0.05). The mean ± SD cinacalcet dose at 72 weeks was 44.0 ± 25.8, 51.7 ± 31.3 and 57.1 ± 37.0 mg for patients with baseline iPTH 301-500, 501-800 or >800 pg/ml, respectively. The main adverse reactions were nausea (5.4%), dyspepsia (5.1%) and vomiting (3.7%). The introduction of cinacalcet improved the routine clinical management of SHPT in a large cohort of Spanish dialysis patients. Cinacalcet is effective and well tolerated regardless of disease severity, and maintains its efficacy over 72 weeks.


CD5 positivity on peripheral blood B lymphocytes in patients with primary Sjögren's syndrome.
The increased number of the CD5+ (Leu 1) B cells in 9 of 17 patients with primary Sjögren's syndrome (SS) were found in this study. The percentage of CD5+ B cells that demonstrated an increased number of these cells was more than 45% in patients with pSS, and the normal level 26.3 +/- 8.8% in control subjects. The ratio of the CD5+ B cells was higher if the pSS was in the active stage.


miR-29 promotes osteosarcoma cell proliferation and migration by targeting PTEN.
Osteosarcoma (OS) is an aggressive malignant neoplasm that arises from primitively transformed cells of mesenchymal origin, and that exhibits osteoblastic differentiation and produces malignant osteoid. MicroRNAs (miRNAs) have been widely reported to have important regulatory roles in various human tumors, including OS. However, the potential mechanism of miR-29 in OS remains largely unknown. miR-29 was highly expressed in OS and overexpression of miR-29 promoted OS cell proliferation, as well as proliferating cell nuclear antigen (PCNA) expression and migration, whereas lower expression of miR-29 inhibited OS cell proliferation, PCNA expression and migration. In the present study, a dual-luciferase reporter system supporting phosphatase and tensin homolog (PTEN) was a target of miR-29 and its expression was inhibited by miR-29 mimic, but increased by miR-29 inhibitor. Overexpression of PTEN inhibited OS cell proliferation and migration and it could attenuate miR-29 promotion effect on OS progression. Overall, the results revealed that miR-29, as a tumor promoter, is involved in OS progression and metastasis by targeting PTEN, indicating that the miR-29/PTEN pathway is a potential therapeutic target for the treatment of OS.


Thyroid and adrenal function in HIV-infected outpatients.
We investigated parameters of thyroid and endocrine functions in 100 HIV-infected men who were grouped according to the CDC criteria. Progression of the disease was associated with a 44% increase in plasma TBG and a 15% increase in plasma CBG, while the T4/TBG ratio was decreased by 20%, plasma DHEAS was lowered by 30% and urinary aldosterone excretion fell by 70%. Plasma T4, T3 and TSH and urinary excretion of cortisol and catecholamines was not influenced by the disease. A weak, but significant negative correlation was found between plasma CBG and the body mass index of the patients. Significant positive correlations were observed between CD-4 cell count and the T4/TBG-ratio or plasma DHEAS levels. TBG was inversely correlated with CD-4 cell count and DHEAS. Thus, an increase in plasma TBG and a shift from adrenal androgen and mineralocorticoid steroid secretion towards cortisol secretion may be endocrine markers for progression of the disease in patients with HIV-infection.


Metabolic responses of channel catfish (Ictalurus punctatus) exposed to phenol and post-exposure recovery.
Metabolic adjustments were studied in channel catfish Ictalurus punctatus exposed to 1.5 mg L-1 of phe nol (10% LC50) for four days and recovered for seven days. Lower triacylglycerol (TGA) stores and increased muscle fat free acids (FFA) suggest fat catabolism in muscle. Remarkable liver FFA decrease (-31%) suggests liver fat catabolism as well. Increased muscular ammonia levels and ASAT (aspartate aminotransferase) and decreased plasma aminoacids suggest higher muscular amino acid uptake. Constant levels of glucose and increased liver glycogen stores, associated with lower amino acids in plasma, indicate gluconeogenesis from amino acids. This is supported by higher hepatic ALAT and ASAT. Higher hepatic LDH followed by lower plasma lactate may indicate that plasma lactate was also used as gluconeogenic substrate. Biochemical alterations were exacerbated during the post-exposure recovery period. Reduction in muscle and plasma protein content indicate proteolysis. A higher rate of liver fat catabolism was resulted from a remarkable decrease in hepatic TGA (-58%). Catabolic preference for lipids was observed in order to supply such elevated energy demand. This study is the first insight about the metabolic profile of I. punctatus to cope with phenol plus its ability to recover, bringing attention to the biological consequences of environmental contamination.


Quantification of t-tubule area and protein distribution in rat cardiac ventricular myocytes.
The transverse (t-) tubules of cardiac ventricular myocytes are invaginations of the surface membrane that form a complex network within the cell. Many of the key proteins involved in excitation-contraction coupling appear to be located predominantly at the t-tubule membrane. Despite their importance, the fraction of cell membrane within the t-tubules remains unclear: measurement of cell capacitance following detubulation suggests approximately 32%, whereas optical measurements suggest up to approximately 65%. We have, therefore, investigated the factors that may account for this discrepancy. Calculation of the combinations of t-tubule radius, length and density that produce t-tubular membrane fractions of 32% or 56% suggest that the true fraction is at the upper end of this range. Assessment of detubulation using confocal and electron microscopy suggests that incomplete detubulation can account for some, but not all of the difference. High cholesterol, and a consequent decrease in specific capacitance, in the t-tubule membrane, may also cause the t-tubule fraction calculated from the loss of capacitance following detubulation to be underestimated. Correcting for both of these factors results in an estimate that is still lower than that obtained from optical measurements suggesting either that optical methods overestimate the fraction of membrane in the t-tubules, or that other, unknown, factors, reduce the apparent fraction obtained by detubulation. A biophysically realistic computer model of a rat ventricular myocyte, incorporating a t-tubule network, is used to assess the effect of the altered estimates of t-tubular membrane fraction on the calculated distribution of ion flux pathways.


Prognostic value of post-procedural aPTT in patients with ST-elevation myocardial infarction treated with primary PCI.
Unfractionated heparin is the most commonly used anticoagulant in ST-elevation myocardial infarction (STEMI) and its effect can be monitored with activated partial thromboplastin time (aPTT). However, the optimal aPTT range during heparin therapy after primary percutaneous coronary intervention (PCI) is yet to be defined. A mean aPTT was calculated of all aPTT measurements in the first 24 hours after pPCI in a total of 1,876 STEMI patients. Mean aPTT measurements were stratified into four categories; < 1.5 times the upper limit of normal (ULN), 1.5 - 2.0 times ULN (the therapeutic group), 2.01 - 3.99 times ULN, and ≥ 4 times ULN. Compared to patients with a therapeutic aPTT, patients with aPTTs < 1.5 times ULN had no increase in recurrent ischaemic events and had similar rates of bleeding complications. Patients with a mean aPTT ≥ 4 times ULN had higher rates recurrent ischaemic and haemorrhagic complications. After multivariable analyses, aPTT ratios ≥ 4 times ULN were no longer associated with recurrent ischaemic events, but remained a strong predictor of severe and moderate bleeding (hazard ratio [HR] 4.64, p = 0.016 and HR 2.27, p = 0.052). In conclusion, in 1,876 STEMI patients treated with pPCI, low aPTTs in the first 24 hours after PCI were not associated with an increase in ischaemic events, whereas high aPTT values were associated with more frequent bleeding complications. These results indicate no clear benefit as well as a safety concern with heparin treatment after primary PCI.


Preprocedure Evaluation of a Dysfunctional Dialysis Access.
Given the many different types of hemodialysis access and the various problems that can occur in each, a structured approach should be taken in the preprocedure evaluation of patients referred for hemodialysis access intervention. Abnormalities detected on surveillance or monitoring trigger referrals for evaluation and intervention in hopes of preventing thrombosis or underdialysis. Familiarity with surveillance and monitoring findings not only facilitates better communication with nephrologists but also helps the interventionalist surmise where the site of stenosis might be and which stenoses are clinically relevant. Additionally, knowing where stenoses are prone to occur (eg, the cephalic arch in brachiocephalic fistulas) and facility with performing and interpreting an on-table ultrasound are important in preprocedure planning.


Expression, translation, and localization of a novel, small growth hormone variant.
A novel transcript of the GH gene has been identified in ocular tissues of chick embryos. It is, however, unknown whether this transcript (small chicken GH, scGH) is translated. This possibility was therefore assessed. The expression of scGH mRNA was confirmed by RT-PCR, using primers that amplified a 426-bp cDNA of its coding sequence. This cDNA was inserted into an expression plasmid to transfect HEK 293 cells, and its translation was shown by specific scGH immunoreactivity in extracts of these cells. This immunoreactivity was directed against the unique N terminus of scGH and was associated with a protein of 16 kDa, comparable with its predicted size. Most of the immunoreactivity detected was, however, associated with a 31-kDa moiety, suggesting scGH is normally dimerized. Neither protein was, however, present in media of the transfected HEK cells, consistent with scGH's lack of a signal sequence. Similar moieties of 16 and 31 kDa were also found in proteins extracted from ocular tissues (neural retina, pigmented epithelium, lens, cornea, choroid) of embryos, although they were not consistently present in vitreous humor. Specific scGH immunoreactivity was also detected in these tissues by immunocytochemistry but not in axons in the optic fiber layer or the optic nerve head, which were immunoreactive for full-length GH. In summary, we have established that scGH expression and translation occurs in ocular tissues of chick embryos, in which its localization in the neural retina and the optic nerve head is distinct from that of the full-length protein.


Epstein-Barr virus and jaw tumors in North Nigeria.
Nigerian patients with tumors of the jaw were compared with controls in respect of antibodies to the viral capsid antigens of Epstein-Barr Virus (EBV) and of total immunoglobulin levels. Immunoglobulin levels did not differ between patients and controls but increased two weeks postsurgery. Immunoglobulin A (IgA) antibodies to EBV were detected in a small number of patients, and mean titers of IgG antibodies to EBV were lower in the patient group, indicating a lack of association between EBV and tumor formation. An association was noted between the presence of Hepatitis B surface antigen, and depressed antibody titers to EBV in patients with tumors. Of 78 patients studied, 12% were Hepatitis B surface antigen positive.


A Comprehensive Evaluation of Obstetrics and Gynecology Residencies' Global Health Training Programs.
To compile a comprehensive summary of obstetrics and gynecology global health training programs and to describe program type, global distribution of work, effect, and reciprocity within programs. This cross-sectional observational study identified all U.S. obstetrics and gynecology residencies with global health training programs, described residency and program characteristics, and evaluated the publications resulting from them. Eligible articles included those published in 2011-2016 about work done in a global health training location by global health training faculty. All eligible articles were evaluated for academic effect. The inclusion of host country authors on articles served as a proxy for reciprocity. Article content was assessed to evaluate whether programs addressed Millennium Development Goals. Among 245 obstetrics and gynecology residencies, 196 (80%) had global health training programs. Location and faculty members were identified for 67 (34%) programs, of which 26 (39%) had global health training faculty who had published articles meeting inclusion criteria. Of 698 articles reviewed, 78% addressed at least one Millennium Development Goal, including 39% that addressed improving maternal health (Millennium Development Goal 5). Approximately half (48%) of authors were from host countries. Most obstetrics and gynecology residencies are offering global health training. The majority of programmatic work addresses Millennium Development Goals and thus is aligned with global health priorities. The effect and reciprocity of global health training programs varies across institutions. Residencies could benefit from internal analysis of their global health training programs to evaluate whether knowledge gained is being disseminated and to ensure equitable partnerships and the creation of sustainable, influential initiatives.


[Untreated homocystinuria in adulthood].
Pronounced osteoporosis was discovered in a 44-year-old man presenting with an herniated intervertebral disk. He reported severe myopia, incomplete dislocation of the lenses and retinal detachment. He did not know of any thrombembolic events in the past. On physical examination Marfan-like appearance and a funnel chest were noted. Because of these findings Marfan syndrome was suspected. Considering the findings of the x-rays, homocystinuria was suspected as a cause of osteoporosis, despite apparently normal cognitive functions. This diagnosis was confirmed by greatly increased values of serum homocysteine and a positive test for urinary homocystine. Since methionine and homocystine were both elevated, the diagnosis of cystathionin-beta-synthase deficiency was established. After taking folate and vitamin B6, the homocysteine level decreased moderately. Betaine and subsequently vitamin B12 were added. Homocysteine values declined markedly on this therapeutic regimen. Two years later the patient was admitted again because of atypical angina. Coronary heart disease could be excluded by coronary angiography. Diagnosis of premature osteoporosis should prompt consideration of homocystinuria even in adults. Premature arteriosclerosis, thrombembolic diseases, dislocation of the lens and retinal detachment may give further clues.


Retained Surgical Foreign Bodies after Surgery.
The problem of retained surgical bodies (RSB) after surgery is an issue for surgeons, hospitals and the entire medical team. They have potentially harmful consequences for the patient as they can be life threatening and usually, a further operation is necessary. The incidence of RSB is between 0.3 to 1.0 per 1,000 abdominal operations, and they occur due to a lack of organisation and communication between surgical staff during the process. Typically, the RSB are surgical sponges and instruments located in the abdomen, retroperitoneum and pelvis.


Vagus Nerve Stimulation.
The vagus nerve stimulation (VNS) is an approach mainly used in cases of intractable epilepsy despite all the efforts. Also, its benefits have been shown in severe cases of depression resistant to typical treatment. The aim of this study was to present current knowledge of vagus nerve stimulation. A new value has emerged just at this stage: VNS aiming the ideal treatment with new hopes. It is based on the placement of a programmable generator on the chest wall. Electric signals from the generator are transmitted to the left vagus nerve through the connection cable. Control on the cerebral bioelectrical activity can be achieved by way of these signal sent from there in an effort for controlling the epileptic discharges. The rate of satisfactory and permanent treatment in epilepsy with monotherapy is around 50%. This rate will increase by one-quarters (25%) with polytherapy. However, there is a patient group roughly constituting one-thirds of this population, and this group remains unresponsive or refractory to all the therapies and combined regimes. The more the number of drugs used, the more chaos and side effects are observed. The anti-epileptic drugs (AEDs) used will have side effects on both the brain and the systemic organs. Cerebral resection surgery can be required in some patients. The most commonly encountered epilepsy type is the partial one, and the possibility of benefiting from invasive procedures is limited in most patients of this type. Selective amygdala-hippocampus surgery is a rising value in complex partial seizures. Therefore, as epilepsy surgery can be performed in very limited numbers and rather developed centres, success can also be achieved in limited numbers of patients. The common ground for all the surgical procedures is the target of preservation of memory, learning, speaking, temper and executive functions as well as obtaining a good control on seizures. However, the action mechanism of VNS is still not exactly known. On the other hand, it appears to be a reliable method that is tolerated well in partial resistant seizures. It has been observed that adverse effects are generally of mild-medium severity, and most of the problems can be eliminated easily through the re-adjustment of the stimulator. VNS, which is a treatment modality that will take place it deserves in epilepsy treatment with "the correct patient" and "correct reason", must be known better and its applications must be developed.


Combined effects of alternariols mixture on human colon carcinoma cells.
Mycotoxins are naturally occurring contaminants encountered at high levels in a wide variety of agricultural products intended for human and animal consumptions. Various Alternaria mycotoxins may occur simultaneously in small grain cereals. Considering the concomitant production of alternariol (AOH) and alternariol monomethyl ether (AME), it is expected that humans and animals are exposed to the mixture rather than to individual compounds. Therefore, we studied the interactive effects of binary mixture of alternariols (AOH and AME) on the human intestinal cell line, HCT116 cells. Exposure of HCT116 cells to low cytotoxic alternariols doses, resulted in a moderate cytotoxicity manifested by a loss in the cell viability mediated by an activation of the mitochondrial apoptotic process, associated with the opening of mitochondrial permeability transition pore (PTP) and the loss of the mitochondrial transmembrane potential (ΔΨm). However, when combined, they exert a significant increase in their toxic potential. Altogether, our study showed that AOH and AME combination is obviously additive.


Interferon alpha-induced modulation of leukocyte cell surface antigens: immunocytofluorometric study with human leukaemia/lymphoma cell lines.
Recombinant interferon alpha enhanced the MHC class I antigen density on human leukaemia/lymphoma cell lines REH, U-937 and HL-60, as measured by immunocytofluorometry using specific monoclonal antibodies. A similar effect was induced (as demonstrated in REH cells), also by human leukocyte interferon-alpha. The latter, however, caused no major alterations in the expression of leukocyte common antigen (ICA; CD45) and transferrin receptor (CD71) in the cell lines examined. In REH cells, there was no interferon-induced alteration of CD10 antigen (CALLA), which in this cell line is markedly down-regulated by 12-0-tetradecanoyl-phorbol-13-acetate (TPA). A decrease of CD4 antigen density on the cell membrane was induced by interferon-alpha in monoblastoid U-937 cells. No induction of MHC class I and II antigens by interferon-alpha was found in K-562 cell subline.


Mesoscale modeling of electrical percolation in fiber-filled systems.
The research described in this paper primarily involves mesoscale simulations: dissipative particle dynamics (DPD) of packed assemblies of oriented fibers suspended in a viscous medium. Computer simulations have been performed in order to explore how the aspect ratio and degree of fiber alignment affect the critical volume fraction (percolation threshold) required to achieve electrical conductivity. The fiber network impedance was assessed using Monte Carlo simulations after establishing the structural arrangement with DPD. The predictions are compared with the predictions of classical percolation theory and found to be in close agreement. The approach is thus validated and can be extended to systems that cannot be tackled analytically; in particular, the work is motivated by long-standing interest in materials which display a complex percolation behavior.


Laparoscopic adhesiolysis for recurrent postoperative small bowel obstruction.
Recurrent small bowel obstruction caused by postoperative adhesions has been treated by conventional laparotomy, however laparoscopic management of acute and recurrent small bowel obstruction has been demonstrated. This study assessed the clinical outcome and long-term efficacy of laparoscopic adhesiolysis for recurrent adhesive small bowel obstruction. Elective laparoscopic treatment following conservative management was attempted in 25 patients hospitalized for recurrent small bowel obstruction after abdominal or pelvic surgery. The pathologic sites of postoperative adhesions and adhesive types were identified laparoscopically in all patients. Complete laparoscopic adhesiolysis was feasible in 18 patients (72%), while conversion to laparoscopic-assisted adhesiolysis (mini-laparotomy with an incision less than 4 cm long) was required in 6 patients (24%) because of dense adhesion or the technical difficulties due to adhesion in the pelvic cavity. Conversion to laparotomy was required for one patient because of excessive adhesions and intestinal perforation (4%). Long-term follow-up was possible in all patients. There was no recurrence of small bowel obstruction over a mean follow-up period of 41 months. Laparoscopic adhesiolysis is a safe and effective treatment for recurrent small bowel obstruction in selected cases. Conversion to mini-laparotomy or laparotomy should be considered in patients with dense or pelvic adhesion.


Is Multitask Deep Learning Practical for Pharma?
Multitask deep learning has emerged as a powerful tool for computational drug discovery. However, despite a number of preliminary studies, multitask deep networks have yet to be widely deployed in the pharmaceutical and biotech industries. This lack of acceptance stems from both software difficulties and lack of understanding of the robustness of multitask deep networks. Our work aims to resolve both of these barriers to adoption. We introduce a high-quality open-source implementation of multitask deep networks as part of the DeepChem open-source platform. Our implementation enables simple python scripts to construct, fit, and evaluate sophisticated deep models. We use our implementation to analyze the performance of multitask deep networks and related deep models on four collections of pharmaceutical data (three of which have not previously been analyzed in the literature). We split these data sets into train/valid/test using time and neighbor splits to test multitask deep learning performance under challenging conditions. Our results demonstrate that multitask deep networks are surprisingly robust and can offer strong improvement over random forests. Our analysis and open-source implementation in DeepChem provide an argument that multitask deep networks are ready for widespread use in commercial drug discovery.


Intergenerational reciprocity and WHO function ability domains predict loneliness in older Chinese adults.
To examine loneliness in old age and whether intergenerational reciprocity and WHO functional ability predicted loneliness. Using the China Health and Retirement Longitudinal Study Wave 4 (2018) database (CHARLS), logistic regression models were adopted to investigate the relationships. The prevalence of loneliness was 28% in older people in China. Corresponding to the five domains of functional abilities, providing financial support to adult children (adj. OR 0.83, 95% CI 0.70-0.99), self-perceived health (adj. OR 1.30, 95% CI 1.19-1.41), having a retirement pension (adj. OR 0.73, 95% CI 0.57-0.93), the ability to decide on taking medications (adj. OR 1.32, 95% CI 1.10-1.58), as well as being able to get up from a chair (adj. OR 1.15, 95% CI 1.02-1.3), and having paid work (adj. OR 0.72, 95% CI 0.54-0.95) were associated with less loneliness. On the contrary, infrequent contact (once a month) with adult children (adj. OR 1.18, 95% CI 1.01-1.38), troubling body pain (adj. OR 1.16, 95% CI 1.10-1.23) and falling since the last interview (adj. OR .23, 95% CI 1.04-1.45) were positively associated with loneliness. In this study, functional abilities of meeting basic needs, making decisions, being mobile and contributing to the support of adult children and society were protective factors for experiencing loneliness in late life. We need to rethink interventions for addressing loneliness in the context of healthy ageing and specific cultural values, taking into account not only providing services to older adults but also supporting them to gain values by contributing to society.


Extraintestinal Applications of Endoscopic Ultrasound.
Since the joining of ultrasonographic and endoscopic technologies in 1980, there has been tremendous advancement in the use of endoscopic ultrasound (EUS). Initially EUS was used mainly to study the anatomic appearance of digestive organs. In the 1990s, with the development of the charge-coupled device, thinner, more flexible scopes were developed that simplified imaging for the endosonographer and improved patient safety. With the development of linear array EUS scopes, biopsies could be performed utilizing fine needle aspiration. Currently, several therapeutic techniques, which were formerly performed through radiologic or surgical procedures, are being safely done with EUS. These include celiac plexus neurolysis and endoscopic drainage of pancreatic cysts. With the advent of miniprobe technology, better delineation of the wall of the gastrointestinal tract can be obtained, facilitating endoscopic mucosal resection. Novel therapeutic uses for EUS are constantly emerging. This article describes the various extraintestinal applications of EUS that have been developed in the last 25 years. More gastroenterologists need training in order to utilize this challenging technology and improve patient access in the local community setting.


Bone and biologically compatible materials in dentistry.
This review focuses on compatible materials that are either implanted in bone tissue to serve as prosthetic devices or used as bone substitutes. It attempts to evaluate the significance of studies of combined osteoconductive materials with osteoinductive factors, like demineralized bone or its purified components, and osteogenic cells. It is important to note that the term osseointegration, which is still widely used by clinicians to indicate the bioactivity of implants in bone healing, is not substantiated by any controlled basic study. Even pure titanium and hydroxyapatite can interfere with the normal healing of a surgical bone wound. This review emphasizes the three-dimensional structure of bone, intercellular communication, and the response of this system to bone damage and materials.


Pyrotinib Combined with Vinorelbine in Patients with Previously Treated HER2-Positive Metastatic Breast Cancer: A Multicenter, Single-arm, Prospective Study.
This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in HER2-positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400mg orally once daily plus vinorelbine 25mg/m2 intravenously or 60-80mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. A total of 39 patients were enrolled. All patients had been pre-treated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3-27.2), and the median PFS was 6.4 months (95%CI, 4.0-8.8). The ORR was 43.6% (95% CI, 27.8%-60.4%) and the DCR was 84.6% (95% CI, 69.5%-94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (P=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.


Retinoblastoma in Asia: Clinical Presentation and Treatment Outcomes in 2112 Patients from 33 Countries.
To describe the clinical presentation and treatment outcomes of children who received a diagnosis of retinoblastoma in 2017 throughout Asia. Multinational, prospective study including treatment-naïve patients in Asia who received a diagnosis of retinoblastoma in 2017 and were followed up thereafter. A total of 2112 patients (2797 eyes) from 96 retinoblastoma treatment centers in 33 Asian countries. Chemotherapy, radiotherapy, enucleation, and orbital exenteration. Enucleation and death. Within the cohort, 1021 patients (48%) were from South Asia (SA), 503 patients (24%) were from East Asia (EA), 310 patients (15%) were from Southeast Asia (SEA), 218 patients (10%) were from West Asia (WA), and 60 patients (3%) were from Central Asia (CA). Mean age at presentation was 27 months (median, 23 months; range, < 1-261 months). The cohort included 1195 male patients (57%) and 917 female patients (43%). The most common presenting symptoms were leukocoria (72%) and strabismus (13%). Using the American Joint Committee on Cancer Staging Manual, Eighth Edition, classification, tumors were staged as cT1 (n = 441 [16%]), cT2 (n = 951 [34%]), cT3 (n = 1136 [41%]), cT4 (n = 267 [10%]), N1 (n = 48 [2%]), and M1 (n = 129 [6%]) at presentation. Retinoblastoma was treated with intravenous chemotherapy in 1450 eyes (52%) and 857 eyes (31%) underwent primary enucleation. Three-year Kaplan-Meier estimates for enucleation and death were 33% and 13% for CA, 18% and 4% for EA, 27% and 15% for SA, 32% and 22% for SEA, and 20% and 11% for WA (P < 0.0001 and P < 0.0001), respectively. At the conclusion of this study, significant heterogeneity was found in treatment outcomes of retinoblastoma among the regions of Asia. East Asia displayed better outcomes with higher rates of globe and life salvage, whereas Southeast Asia showed poorer outcomes compared with the rest of Asia. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


[Adenomatoid tumor of the right adrenal gland: a case report].
Adenomatoid tumor of adrenal gland is a very rare primary tumor with favourable prognosis. The mesothelial origin of this tumor was confirmed by multiple studies of various authors. This origin was proven by immunohistochemical and ultrastructural examinations. In our case report, we present an interesting case of the adenomatoid tumor of the right adrenal gland in a 55-year-old woman. Our case is the second well-documented case of this tumor occurring in a female adult patient. We emphasize the presence of an intraluminal thread-like bridging strands, generally considered to be a characteristic histologic feature of this tumor, which have not yet been reported in literature in adenomatoid tumor located in adrenal glands.


Does the Delivery of CBT for Youth Anxiety Differ Across Research and Practice Settings?
Does delivery of the same manual-based individual cognitive-behavioral treatment (ICBT) program for youth anxiety differ across research and practice settings? We examined this question in a sample of 89 youths (M age = 10.56, SD = 1.99; 63.70% Caucasian; 52.80% male) diagnosed with a primary anxiety disorder. The youths received (a) ICBT in a research setting, (b) ICBT in practice settings, or (c) non-manual-based usual care (UC) in practice settings. Treatment delivery was assessed using four theory-based subscales (Cognitive-behavioral, Psychodynamic, Client-Centered, Family) from the Therapy Process Observational Coding System for Child Psychotherapy-Revised Strategies scale (TPOCS-RS). Reliable independent coders, using the TPOCS-RS, rated 954 treatment sessions from two randomized controlled trials (1 efficacy and 1 effectiveness trial). In both settings, therapists trained and supervised in ICBT delivered comparable levels of cognitive-behavioral interventions at the beginning of treatment. However, therapists trained in ICBT in the research setting increased their use of cognitive-behavioral interventions as treatment progressed whereas their practice setting counterparts waned over time. Relative to the two ICBT groups, the UC therapists delivered a significantly higher dose of psychodynamic and family interventions and a significantly lower dose of cognitive-behavioral interventions. Overall, results indicate that there were more similarities than differences in manual-based ICBT delivery across research and practice settings. Future research should explore why the delivery of cognitive-behavioral interventions in the ICBT program changed over time and across settings, and whether the answers to these questions could inform implementation of ICBT programs.


Removal forces and adhesion properties of Saccharomyces cerevisiae on glass substrates probed by optical tweezer.
In agroindustry, the hygiene of solid surfaces is of primary importance in order to ensure that products are safe for consumers. To improve safety, one of the major ways consists in identifying and understanding the mechanisms of microbial cell adhesion to nonporous solid surfaces or filtration membranes. In this paper we investigate the adhesion of the yeast cell Saccharomyces cerevisiae (about 5 mum in diameter) to a model solid surface, using well-defined hydrophilic glass substrates. An optical tweezer device developed by Piau [J. Non-Newtonian Fluid Mech. 144, 1 (2007)] was applied to yeast cells in contact with well-characterized glass surfaces. Two planes of observation were used to obtain quantitative measurements of removal forces and to characterize the corresponding mechanisms at a micrometer length scale. The results highlight various adhesion mechanisms, depending on the ionic strength, contact time, and type of yeast. The study has allowed to show a considerable increase of adhering cells with the ionic strength and has provided a quantitative measurement of the detachment forces of cultured yeast cells. Force levels are found to grow with ionic strength and differences in mobility are highlighted. The results clearly underline that a microrheological approach is essential for analyzing the adhesion mechanisms of biological systems at the relevant local scales.


Whole-Genome Shotgun Sequencing of Cephalosporin-Resistant Salmonella enterica Serovar Typhi.
Typhoid is one of the leading causes of mortality in developing countries. Here, we report the draft genome sequences of four Salmonella enterica serovar Typhi strains isolated from bloodstream infections in a tertiary care hospital. The sequence data indicate genomes of ~4.5 Mb for all isolates, with one plasmid in each.


Rigor in health-related research: toward an expanded conceptualization.
When the research process is viewed not merely as a set of methods for data collection and analysis but, instead, as an integrated series of arbitrary choices made by the researcher, it quickly becomes apparent that the prevailing conceptualization of rigor is much too narrow; indeed, the way rigor is currently conceptualized may well be responsible for the many errors that are commonly made in the research process. An expanded conceptualization of rigor is presented, and its implications for research into some critical health issues are discussed in some detail.


Routine coronary angiographic follow-up and subsequent revascularization in patients with acute myocardial infarction.
The aims of the present study are to: (1) clarify the angiographic follow-up (AFU) rate after discharge; (2) elucidate the characteristics of those undergoing it; and (3) determine the impact of AFU on subsequent revascularization procedures among patients with acute myocardial infarction (AMI). Three thousand and twenty-one consecutive patients presenting within 48 h of AMI onset were enrolled from 17 centers in Japan between January 1999 and June 2001. To clarify the frequency of AFU and their characteristics, 2736 patients who survived at discharge were analyzed. Among 1160 patients matched by propensity score, the impact of AFU on subsequent revascularization was analyzed. Of 2736 patients, 1367 (50%) underwent AFU and constituted the lower-risk population. Of the 580 matched patient pairs, 120 (21%) in the clinical follow-up group and 198 (34%) in the AFU group underwent subsequent revascularization (hazard ratio 7.54; 95% confidence interval 5.74-9.91). Of the 198 patients in the AFU group, 157 (79%) underwent revascularization at the discretion of the responsible physician based on angiographic findings. Angiographic follow-up led to more subsequent revascularization. More evidence would be necessary to determine the effectiveness and the methods by which patients are selected.


[Bromocriptine in chemotherapy-resistant, metastatic breast cancer. Results of the GO-MC-BROMO 2/82 AIO Study].
In a case report a patient with metastatic breast cancer, who had chemotherapy resistance and hyperprolactinemia, showed a tumor remission following suppression of elevated prolactin levels with bromocriptine. Based on this observation, 18 patients with progressive metastatic breast cancer, chemotherapy resistance and hyperprolactinemia were treated with 10 mg bromocriptine/day in a prospective study. This treatment was in addition to chemotherapy, which was continued for 8 weeks in spite of progressive disease. In all patients, elevated prolactin levels (arithmetic mean 1388 +/- 201 mU/l before treatment) were suppressed to values under 100 mU/l. A partial remission was observed in one single patient which was not clearly attributed to suppression of plasma prolactin levels, but to delayed tumor remission. Side effects, mainly gastrointestinal disorders, were observed in all patients during therapy. In 6/18 patients treatment had to be stopped before end of study due to intolerable nausea and vomiting. It is concluded that suppression of elevated prolactin levels in progressive metastatic breast cancer patients is not effective in restoring tumor sensitivity to chemotherapy.


Retrospective Analysis of COVID-19 Conversion Rate Among Anesthesiologists in Acute Care Centers.
Brief description of the primary research objective Among healthcare workers, anesthesiologists are regarded as frequently exposed frontline providers in the fight against COVID-19 due to their proximity to patient airways and involvement in aerosolized procedures. As such, the risk of contracting the COVID-19 virus as an occupational hazard is presumed to be higher. To date, in most published studies, all healthcare workers were grouped together, independent of specialty or profession. At the time that this survey was distributed, we did not find any peer-reviewed articles that differentiated COVID-19 infection rates among frontline, such as anesthesiologists vs. non-frontline healthcare workers. This retrospective survey's primary research objective was to report the rate of COVID-19 infection among anesthesiologists compared to the general population of healthcare workers. Methodology A survey was sent among anesthesiology attendings and residents in Northern New Jersey and Brooklyn, New York hospitals on duty during the peak pandemic from March 2020 to May 2020. Questions in the survey focused on infection rates and adherence to standards of infection precaution and personal protective equipment (PPE) utilization. Main Findings This retrospective study highlights the rate of infection among anesthesiologists as a particularly vulnerable subgroup of frontline residents and physicians, as they are called to duty when emergent airway management is required. In our study, the reported rate of contracting COVID-19 among anesthesiologists was 16.7%. This statistic is higher than the infection rates published by studies by New York State and the CDC. Conclusion The survey sent to anesthesiologists is useful to understand the impact of COVID-19 on this subgroup of frontline providers and the importance of adhering to standards of infection protocol and the role of PPE.


Surface characteristics and adhesion of Escherichia coli and Staphylococcus epidermidis.
Surface hydrophobicity, surface electrokinetic potential and the ability to adhere to nitric-acid cleansed glass surfaces has been assessed throughout the growth, in batch culture, of Escherichia coli and Staphylococcus epidermidis. In both instances adhesiveness and surface hydrophobicity decreased in early- to mid-exponential phase. Cell surface charge, on the other hand became more electro-negative for E. coli but electro-neutral for Staph. epidermidis as the cells proceeded to divide. Adhesiveness correlated directly with surface electronegativity and hydrophobicity for Staph. epidermidis but inversely with surface electro-negativity for E. coli.


[Anaesthesia-related Infection Prevention during Operations].
The processes of anaesthesia during operations enable surgical disciplines to perform a wide range of procedures. However, anaesthesia procedure may also represent a potential risk of infection for the surgical patient. Important hygiene measures concern the following topics: hand hygiene, surface disinfection, administration of parenteral drugs, dealing with catheters, intubation, perioperative antibiotic prophylaxis, temperature management, change intervals, OR workflow organization. The selection of hygiene measures for anaesthesia staff in the operating theatre listed in this article is presented in the sequence of the work flow, whereby certain topics such as hand hygiene naturally play an important role in all work phases.


Developmental characteristics of pectoralis muscle in Pekin duck embryos.
To confirm the entire developmental process and transition point of embryonic Pekin duck pectoral muscle, and to investigate the association between pectoral muscle development and their regulating genes, anatomical and morphological analyses of embryonic Pekin duck skeletal muscles were performed, and the expression patterns of its regulating genes were investigated. The anatomical analysis revealed that body weight increased with age, while increases in pectoral muscle weight nearly ceased after the embryo was 20 days of hatching (E20). The developmental morphological characteristics of Pekin duck pectoral muscle at the embryonic stage showed that E20 was the transition point (from proliferation to fusion) of Pekin duck pectoral muscle. The expression patterns of MRF4, MyoG, and MSTN indicated that E19 or E20 was the fastest point of pectoral muscle development and the crucial transition for Pekin duck pectoral muscle development during the embryonic stage. Together, these findings imply that E20 is the crucial transition point (from proliferation to fusion) of Pekin duck pectoral muscle and that there is no muscle fiber hypertrophy after E20. Results of this study provide further understanding of the developmental process and transition point of Pekin duck pectoral muscle during the embryo stage.


Stable isotope dilution techniques for assessing vitamin A status and bioefficacy of provitamin A carotenoids in humans.
Vitamin A deficiency is a major global public health problem. Among the variety of techniques that are available for assessing human vitamin A status, evaluating the provitamin A nutritional values of foodstuffs and estimating human vitamin A requirements, isotope dilution provides the most accurate estimates. Although the relative expense of isotope dilution restricts its applications, it has an important function as the standard of reference for other techniques. Mathematical modelling plays an indispensable role in the interpretation of isotope dilution data. This review summarises recent applications of stable isotope methodology to determine human vitamin A status, estimate human vitamin A requirements, and calculate the bioconversion and bioefficacy of food carotenoids.


Bone Mesenchymal Stem Cell-Derived sEV-Encapsulated Thermosensitive Hydrogels Accelerate Osteogenesis and Angiogenesis by Release of Exosomal miR-21.
Angiogenesis has been recognized to play an essential role in remodeling new bone (osteogenesis). Small extracellular vesicles (sEVs), the endogenously secreted nanovesicles by cells, exhibit great potential in the regeneration of bone defects and the realization of cell-free therapy. Chitosan, a natural polysaccharide, can form a thermosensitive injectable hydrogel through the addition of β-glycerophosphate. Herein, we developed injectable thermosensitive hydrogel-encapsulated sEVs derived from bone mesenchymal stem cells, which significantly prolonged delivery and release and synergistically enhanced bone regeneration. sEVs were isolated and characterized, and the physicochemical properties, release kinetics, and biocompatibility of the hydrogels were analyzed. In vitro experiments were performed to investigate osteogenic differentiation, cell proliferation and migration, and tube formation. Thereafter, sEVs were added to the chitosan/β-glycerophosphate hydrogel (sEV@CS/β-GP composite) to repair calvarial defects in rats. The results showed that sEV-loaded hydrogels were biocompatible, exhibiting excellent thermosensitive properties and enhancing bone regeneration. Furthermore, mechanistic studies revealed that exosomal miR-21 targeted SPRY2, thereby promoting angiogenesis. Our study provides new insights on the repair of bone defects with multifunctional controlled-sEV-release hydrogels, which shows great potential in the repair of tissues in the future.


Direct Transformation of Terminal Alkynes into Amidines by a Silver-Catalyzed Four-Component Reaction.
An unprecedented conversion of terminal alkynes into N-sulfonimidamides (amidines) is reported by a silver-catalyzed, one-pot, four-component reaction with TMSN3, sodium sulfinate, and sulfonyl azide. The reaction scope includes both aromatic and aliphatic alkynes. A possible cascade reaction mechanism, consisting of alkyne hydroazidation, sulfonyl radical addition, 1,3-dipolar cycloaddition by TMSN3, and retro-1,3-dipolar cycloaddition, is proposed. TMSN3 is found to play an essential role in each step of the reaction.