Intestinal co-infection by Cyclospora sp. and Cryptosporidium parvum: first report in an AIDS patient.
Cyclospora is recently described new human pathogenic coccidian causing intermittent diarrhoeal enteritis which may persist for weeks or months in immunocompetent subjects, particularly travellers visiting some tropical areas and countries, such as Nepal, the Caribbean, Peru and Mexico. More rarely this enteric pathogen affects immunocompromised humans, namely HIV-infected people or AIDS patients, with some clinical pictures recognized in normal hosts. We describe the first case of Cyclospora sp. and Cryptosporidium parvum associated diarrhoeal enteritis in an adult AIDS patient.


Extensive structural remodeling of the injured spinal cord revealed by phosphorylated MAP1B in sprouting axons and degenerating neurons.
Spinal cord injury (SCI) results in loss of sensory and motor function because injured axons do not regenerate and neurons that die are not replaced. Nevertheless, there is evidence for spontaneous reorganization of spared pathways (i.e. sprouting) that could be exploited to improve functional recovery. The extent of morphological remodeling after spinal cord injury is, however, not understood. We have previously shown that a phosphorylated form of microtubule-associated protein-1B, MAP1B-P, is expressed by growing axons, but is detected in intact adult SC in fibers exhibiting a somatotopic distribution of myelinated sensory fibers. We now demonstrate that after adult SCI, MAP1B-P is up-regulated in other classes of axons. We used immunohistochemistry to show changing levels and distributions of MAP1B-P after a right thoracic hemisection of adult rat spinal cord. MAP1B-P labeling suggests rearrangements of the axonal circuitry that go well beyond previous descriptions. MAP1B-P-positive fibers are present in ectopic locations in gray matter in both dorsal and ventral horns and around the central canal. Double staining reveals that primary sensory and descending serotonergic and corticospinal axons are MAP1B-P positive. In white matter, high MAP1B-P expression is found on terminal enlargements near the injury, reflecting retraction of transected axons. MAP1B-P also accumulates in pre-apoptotic neuronal somata axotomized by the lesion, indicating association of MAP1B-P not only with axon extension and retraction, but also with neuronal degeneration. Finally, we provide evidence that MAP1B phosphorylation is correlated with activation of JNK MAP-kinase, providing a step towards unraveling the mechanisms of regulation of this plasticity-related cytoskeletal protein.


Sex Differences in Major Depressive Disorder (MDD) and Preclinical Animal Models for the Study of Depression.
Depression and related mood disorders constitute an enormous burden on health, quality of life, and the global economy, and women have roughly twice the lifetime risk of men for experiencing depression. Here, we review sex differences in human brain physiology that may be connected to the increased susceptibility of women to major depressive disorder (MDD). Moreover, we summarize decades of preclinical research using animal models for the study of mood dysfunction that uncover some of the potential molecular, cellular, and circuit-level mechanisms that may underlie sex differences and disease etiology. We place particular emphasis on a series of recent studies demonstrating the central contribution of the circuit projecting from ventral hippocampus to nucleus accumbens and how inherent sex differences in the excitability of this circuit may predict and drive depression-related behaviors. The findings covered in this review underscore the continued need for studies using preclinical models and circuit-specific strategies for uncovering molecular and physiological mechanisms that could lead to potential sex-specific diagnosis, prognosis, prevention, and/or treatments for MDD and other mood disorders.


Subjective effects of combined-axis vibration: comparison of Y-axis and Y-plus-roll vibrations.
A psychophysical matching experiment was conducted to compare the perceived intensity of Y-axis and Y-plus-roll vibrations. Seated subjects matched their perceptions of the intensity of single-axis stimulus vibrations in the Y-axis, or combined-axis stimulus vibrations made up of Y-axis and roll motions, by adjusting the intensity of a sinusoidal, 5 Hz, Z-axis response vibration. Stimulus vibrations were sinusoidal at 3.15, 4, 5, 6.3, and 8 Hz. For each frequency, both types of stimulus vibrations were presented at three acceleration levels related to three axis-to-seat distances for the roll vibrations. The results showed that as frequency increased the acceleration of the Z-axis matching response decreased for both types of stimuli. In addition, as stimulus acceleration (axis-to-seat distance) increased, response acceleration showed substantial increases at every frequency. However, the matching responses showed only minor differences due to vibration type, indicating that the effects of roll vibrations can be accounted for in terms of the Y-axis translational vibrations produced at the subject's seat.


Gene therapy of mitochondrial DNA mutations: a brief, biased history of allotopic expression in mammalian cells.
Successful treatment of mitochondrial DNA (mtDNA) mutations might be possible by construction of mtDNA-encoded protein genes so that they can be inserted into the nuclear genome and the protein expressed in the mitochondria (allotopic expression). This technique would require individual assembly of all 13 mtDNA-encoded protein genes with an aminoterminal leader peptide that directs the cytoplasmic translated protein to the mitochondrial membrane. The 13 allotopic genes could be inserted into the nuclear genome of a patient's stem cell that had been "cured" of its nascent mtDNA via ethidium bromide treatment (rho-zero cell). The rho-zero cell would be a uridine auxotroph, and recovery from uridine auxotrophy would indicate successful transformation. The patient's own cells could then be returned to the patient's body. With a selective advantage of recovered oxidative phosphorylation, the transformed cells could replace cells with mtDNA mutations. Results of experiments by us on allotopically expressed CHO ATPase6 and of experiments by other workers suggest that there might be competition with endogenous mtDNA-encoded proteins if the particular protein gene is not removed from the endogenous mitochondrial genomes. Thus, it is likely that all 13 mtDNA-encoded protein genes will need to be allotopically expressed, with concomitant removal of all mtDNA genomes, in order for this form of mtDNA gene therapy to be successful.


EFNB2 acts as the target of miR-557 to facilitate cell proliferation, migration and invasion in pancreatic ductal adenocarcinoma by bioinformatics analysis and verification.
This study aims to identify the pivotal microRNAs (miRNAs) and genes, and their potential regulatory mechanisms in pancreatic ductal adenocarcinoma (PDAC) through bioinformatics analysis and experimental verification. We comprehensively analyzed two miRNA microarray datasets (GSE32678 and GSE43796) and three gene microarray datasets (GSE28735, GSE41368 and GSE71989), which were downloaded from the Gene Expression Omnibus (GEO) database, and identified the total of 8 differentially expressed miRNAs (DEMs) and 257 differentially expressed genes (DEGs) in common. Next, a new miRNA-mRNA regulatory network was constructed by bioinformatics methods, including 7 miRNAs, 58 putative target genes and 80 interaction pairs of miRNA-mRNA. Scrutinized by OncoLnc and GEPIA, it was found that 3 of 7 miRNAs (miR-21, miR-196b and miR-203) and 20 of 58 genes (MXRA5, EPYC, ECT2, COL12A1, SLC6A14, SLC7A2, BTG2, PDK4, CTNND2, NRP2, PXDN, CD109, TGFBI, LRRN1, ITGA2, DKK1, GREM1, EFNB2, SEMA3C and NT5E) were notably associated with prognosis in patients with PDAC. Furthermore, EFNB2 was significantly upregulated in PDAC compared with normal controls from different public databases. Cellular function experiments demonstrated that EFNB2 knockdown inhibited cell proliferation, migration and invasion in SW1990 cells. Western blot and luciferase reporter assays revealed that miR-557 negatively regulated the expression of EFNB2 by directly binging its 3' UTR. In conclusion, we performed integrated analysis for multiple expression profiles, and provided novel candidate miRNAs and genes to be exploited for functional studies. In addition, our findings suggested that EFNB2 contributes to PDAC progression by acting as the target gene of miR-557. It is useful for uncovering miRNA-based treatments in PDAC.


COVID-19 Incidence After Emergency Department Visit.
The emergency department (ED) at the Veterans Affairs Greater Los Angeles Healthcare System (VAGLAHS) saw a decrease in the number of visits during the early stages of the COVID-19 pandemic. Little is known whether risk mitigation procedures may help reduce the spread of COVID-19 infections for veterans visiting the ED. Therefore, we reviewed patient visits to the ED for diagnoses other than COVID-19 to assess whether these patients had an increased COVID-19 positivity rate within 21 days of the initial visit. Risk mitigation procedures instituted by the VAGLAHS ED included a COVID-19 outdoor testing tent, immediate isolation of persons under investigation for COVID-19, disinfection protocols between high-risk patient encounters, dedicated training in donning and doffing personal protective equipment, implementation of 2-physician airway teams for COVID-19 intubations, use of electronic tablets to communicate with COVID-19 patients, and implementation of social distancing initiatives in the waiting room to minimize COVID-19 exposures. The average positivity rate at the VAGLAHS ED during this time frame was 0% to 6.7%, compared with 6.9% to 33.3% within the wider VAGLAHS. Implementing risk mitigation procedures in the VAGLAHS ED helped minimize exposure and subsequent diagnosis of COVID-19 for veterans who visited the VAGLAHS ED for symptoms not associated with COVID-19 infection. Seeking acute medical care in the ED did not put patients at higher risk of contracting COVID-19.


Association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) shares genetic and cytokine profiles with other autoinflammatory diseases.
The association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) has recently been described and suggested to be a new entity within the spectrum of autoinflammatory syndromes, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T-cells. We conducted an observational study on 5 patients with PASH syndrome, analyzing their clinical features, genetic profile of 10 genes already known to be involved in autoinflammatory diseases (AIDs), and cytokine expression pattern both in lesional skin and serum. In tissue skin samples, the expressions of interleukin (IL)-1β and its receptors I and II were significantly higher in PASH (P = 0.028, 0.047, and 0.050, respectively) than in controls. In PASH patients, chemokines such as IL-8 (P = 0.004), C-X-C motif ligand (CXCL) 1/2/3 (P = 0.028), CXCL 16 (P = 0.008), and regulated on activation, normal T cell expressed and secreted (RANTES) (P = 0.005) were overexpressed. Fas/Fas ligand and cluster of differentiation (CD)40/CD40 ligand systems were also overexpressed (P = 0.016 for Fas, P = 0.006 for Fas ligand, P = 0.005 for CD40, and P = 0.004 for CD40 ligand), contributing to tissue damage and inflammation. In peripheral blood, serum levels of the main proinflammatory cytokines, that is, IL-1β, tumor necrosis factor-α, and IL-17, were within the normal range, suggesting that in PASH syndrome, the inflammatory process is mainly localized into the skin. Four out of our 5 PASH patients presented genetic alterations typical of well-known AIDs, including inflammatory bowel diseases, and the only patient lacking genetic changes had clinically evident Crohn disease. In conclusion, overexpression of cytokines/chemokines and molecules amplifying the inflammatory network, along with the genetic changes, supports the view that PASH syndrome is autoinflammatory in origin.


[Under cover penetrating keratoplasty: a safer technique, especially for children].
Penetrating keratoplasty is usually performed when the cornea has lost all transparency Irrespective of the instruments used, the most awkward step occurs when the cornea is removed. In aphakic and infant eyes there is a high risk of lens expulsion, vitreous loss, or choroidal effusion. Under-cover penetrating keratoplasty never leaves the anterior segment exposed, and is therefore safer for infant and aphakic eyes and when large-diameter trepanation is necessary.


Erlotinib resistance in EGFR-amplified glioblastoma cells is associated with upregulation of EGFRvIII and PI3Kp110δ.
The treatment efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors like erlotinib has not met expectations for glioblastoma therapy, even for EGFR-overexpressing tumors. We determined possible mechanisms of therapy resistance using the unique BS153 glioblastoma cell line, which has retained amplification of the egfr gene and expression of EGFR variant (v)III. Functional effects of erlotinib, gefitinib, and cetuximab on BS153 proliferation, migration, and EGFR-dependent signal transduction were systematically compared in vitro. The tumor-initiating capacity of parental and treatment-resistant BS153 was studied in Naval Medical Research Institute/Foxn1(nu) mice. Potential mediators of resistance were knocked down using small interfering (si)RNA. Erlotinib and gefitinib inhibited proliferation and migration of BS153 in a dose-dependent manner, whereas cetuximab had no effect. BS153 developed resistance to erlotinib (BS153(resE)) but not to gefitinib. Resistance was associated with strong upregulation of EGFRvIII and subsequent activation of the phosphatidylinositol-3-OH kinase (PI3K) pathway in BS153(resE) and an increased expression of the regulatory 110-kDa delta subunit of PI3K (p110δ). Knockdown of EGFRvIII in BS153(resE) largely restored sensitivity to erlotinib. Targeting PI3K pharmacologically caused a significant decrease in cell viability, and specifically targeting p110δ by siRNA partially restored erlotinib sensitivity in BS153(resE). In vivo, BS153 formed highly invasive tumors with an unusual growth pattern, displaying numerous satellites distant from the initial injection site. Erlotinib resistance led to delayed onset of tumor growth as well as prolonged overall survival of mice without changing tumor morphology. EGFRvIII can mediate resistance to erlotinib in EGFR-amplified glioblastoma via an increase in PI3Kp110δ. Interfering with PI3Kp110δ can restore sensitivity toward the tyrosine kinase inhibitor.


Photobiomodulation therapy with light-emitting diode in stimulating adipose tissue mitochondria.
Low-level laser therapy (LLLT) is known for its ability to induce a photochemical process, primarily targeting mitochondria, a process referred to as photobiomodulation (PBM). Recently, its use has been attributed as an adjunct in obesity treatment, to stimulate lipolysis and apoptosis. However, the pathway of stimulation remains uncertain. Thus, the objective of this study was to understand whether mitochondrial stimulation occurs in adipose tissue cells after PBM therapy, which could lead to the processes of lipolysis and apoptosis. A non-randomized clinical trial was conducted using a split abdomen design in obese women who received red and infrared LED photobiomodulation therapy (PBMT). The patients underwent bariatric surgery, and adipose tissue samples were collected for immunohistochemical analysis with primary mitochondrial antibodies. Adipose tissue samples subjected to LED intervention exhibited positivity in mitochondrial antibodies for cAMP, DRP1, FAS, FIS1, MFN2, and OPA1 (p<0.001) compared to the control group. In conclusion, we observed that PBMT was capable of generating mitochondrial stimulation in adipose tissue cells, as evidenced by the positive antibody signals. This finding suggests that mitochondrial stimulation could be the mechanism and action underlying adipose tissue lipolysis and apoptosis.


MicroRNA-525 enhances chondrosarcoma malignancy by targeting F-spondin 1.
Increasing evidence has suggested that microRNAs (miRNAs; miRs) are extensively involved in the progression of chondrosarcoma (CHS). However, few studies have investigated the functional role of miR-525 in CHS tissues and cells. In the present study, it was discovered that miR-525 levels were decreased in CHS tissues and cells. Dual luciferase assays indicated that F-spondin 1 (SPON1) is a target gene of microRNA (miR)-525. In addition, miR-525 overexpression suppressed SW1353 cell migration and invasion and enhanced SW1353 cell apoptosis. Increased SPON1 expression levels were identified in CHS tissues and cell lines. Furthermore, miR-525 overexpression significantly suppressed the activation of focal adhesion kinase (FAK)/Src/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) signaling in CHS cells; this suppression led to SPON1 silencing. In comparison, the SPON1 knockdown-mediated inactivation of FAK/Src/PI3K/Akt signaling was inhibited by inhibiting miR-525. In summary, the present study revealed that decreased miR-525 levels could enhance CHS malignancy as decreased miR-525 binding to the 3' untranslated region of SPON1 activates FAK/Src/PI3K/Akt signaling.


High Mobility in Nanocrystal-Based Transparent Conducting Oxide Thin Films.
Charge carrier mobility in transparent conducting oxide (TCO) films is mainly limited by impurity scattering, grain boundary scattering, and a hopping transport mechanism. We enhanced the mobility in nanocrystal (NC)-based TCO films, exceeding even typical values found in sputtered thin films, by addressing each of these scattering factors. Impurity scattering is diminished by incorporating cerium as a dopant in indium oxide NCs instead of the more typical dopant, tin. Grain boundary scattering is reduced by using large NCs with a size of 21 nm, which nonetheless were sufficiently small to avoid haze due to light scattering. In-filling of the precursor solution followed by annealing results in a NC-based composite film which conducts electrons through metal-like transport at room temperature, readily distinguished by the positive temperature coefficient of resistance. Cerium-doped indium oxide (Ce:In2O3) NC-based composite films achieve a high mobility of 56.0 cm2/V·s, and a low resistivity of 1.25 × 10-3 Ω·cm. The films are transparent to a broad range of visible and near-infrared light from 400 nm to at least 2500 nm wavelength. On the basis of the high conductivity and high transparency of the Ce:In2O3 NC-based composite films, the films are successfully applied as transparent electrodes within an electrochromic device.


Phenotypic and genotypic determinants of mupirocin resistance among Staphylococcus aureus isolates recovered from clinical samples of children: an Iranian hospital-based study.
The aim of this study was to evaluate both phenotypic and genotypic determinants of mupirocin resistance among methicillin-resistant Staphylococcus aureus (MRSA) and methicillin susceptible S. aureus (MSSA) strains recovered from different clinical samples of children who were admitted to the Children's Medical Center (CMC) Hospital, Tehran, Iran. A total of 120 clinical isolates of S. aureus were collected from the microbiology laboratory of CMC Hospital. Antimicrobial susceptibility of the isolates to different antimicrobial agents was determined by disk diffusion method. The methicillin resistance phenotype (MRSA) was identified using a 30 µg cefoxitin disk. The minimum inhibitory concentration (MIC) of mupirocin was determined by broth microdilution method. Strains with mupirocin MIC between 8 and 256 µg/mL were considered as low-level mupirocin resistant (LLMR), and strains with an MIC≥512 µg/mL were considered as high-level mupirocin resistant (HLMR). The presence of genes encoding HLMR (ie, mupA and mupB genes) was evaluated by PCR method. Four out of 120 isolates (3%) had mupirocin MIC≥512 µg/mL and were HLMR; however, no LLMR isolate was detected. Fifty-two isolates (43%) were MRSA, and there were no differences in the distribution of mupirocin resistance among MRSA and MSSA isolates (P>0.05). The PCR method identified mupA gene in two out of four HLMR isolates, and mupB gene was not detected in any HLMR isolates. Because of discrepancies between the phenotypic and genotypic patterns of mupirocin resistance and due to the avoidance of false-negative results, it is better to determine the mupirocin resistance by both antibiotic susceptibility tests and PCR method. Considering the increasing need of mupirocin for the control of S. aureus infections, continuous checking of its susceptibility status is necessary.


Dental students' attitudes toward tobacco cessation counseling.
The main objective of this study was to determine if level of education, gender, and tobacco history affected attitudes of dental students toward tobacco cessation counseling. A secondary objective was to examine the psychometric properties of the survey instrument. First- and fourth-year dental students at one school of dental medicine completed a survey examining attitudes toward tobacco cessation and perceived barriers to performing tobacco cessation counseling in a dental setting. Analyses were conducted to determine whether there were differences in attitudes by gender, level of education, or personal and family tobacco use. A main effect for education level was discovered. Fourth-year students were more likely than first-year students to consider the prescription of nicotine gum and transdermal patches to be within the scope and responsibility of the dental profession. No significant differences were seen with regard to gender or students' personal and family tobacco histories. Dental students were in general agreement that tobacco cessation counseling is within the responsibility of the dental profession, is within the scope of dental practice, and can be effective. Psychometric analysis revealed reliability of the survey instrument.


Relationship between serum parathyroid hormone, serum calcium and arterial blood pressure in patients with primary hyperparathyroidism: results of a multivariate analysis.
To evaluate the possible relationship between serum calcium, serum parathyroid hormone (PTH) levels and arterial blood pressure (BP) in patients with primary hyperparathyroidism (HPT). A retrospective population-based study. Charts of 194 patients with proven primary HPT were reviewed, and the main clinical and biochemical parameters were recorded. There were 48 men (24.7%) and 146 women (75.3%), with a median age of 59 years (range 23-82 years). Patients who used antihypertensive drugs or hormone replacement therapy had been previously excluded. All patients underwent successful parathyroidectomy, and were cured of their disease. There were no differences (P=NS) between men and women in systolic (143.3+/-19.1 vs 145.4+/-17.1 mmHg) and diastolic (87.1+/-12.3 vs 88.4+/-9.9 mmHg) BP, and in the main biochemical parameters. A significant (P<0.01) correlation was found between (i) serum calcium and serum PTH levels (r=0.39, F=88.36), (ii) age and BP, both systolic (r=0.61, F=118.16) and diastolic (r=0.48, F=64.5), and (iii) body mass index (BMI) and BP (r=0.45 and 0.36 respectively). There was no significant association of serum calcium levels with systolic (r=0.0974, t=1.3422, P=0.18) or diastolic (r=0.1117, t=1.5409, P=0.12) BP, and of serum PTH levels with systolic (r=-0.0349, t=-0.4783, P=0.63) or diastolic (r=-0.0793, t=-1.0913, P=0.28) BP. Multivariate analysis confirmed that none of the independent biochemical parameters significantly correlated with BP, both systolic and diastolic. In patients with primary HPT there is no relationship between PTH, calcium and BP. Thus, in hyperparathyroid patients, BP should be considered as an independent variable, mainly related to age and BMI.


Efficacy of combined treatment with pasireotide, pegvisomant and cabergoline in an acromegalic patient resistant to other treatments: a case report.
The approach to acromegalic patients with persistent acromegaly after surgery and inadequate response to first-generation somatostatin receptor ligands (SRLs) should be strictly tailored. Current options include new pituitary surgery and/or radiosurgery, or alternative medical treatment with SRLs high dose regimens, pegvisomant (PEG) as monotherapy, or combined therapy with the addition of PEG or cabergoline to SRLs. A new pharmacological approach includes pasireotide, a second-generation SRL approved for patients who do not adequately respond to surgery and/or for whom surgery is not an option. No reports on efficacy and safety of combined therapy with pasireotide and pegvisomant (PEG) in acromegaly are available. Here we report the case of a 41-year-old acromegalic man with a mixed GH/PRL pituitary adenoma post-surgical resistant to first-generation SRLs both alone and in combination with cabergoline and PEG who achieved biochemical and tumor control with the combined triple treatment with pasireotide, PEG and cabergoline without adverse events and with a good compliance to treatment. Twelve months of therapy with pasireotide, PEG and cabergoline proved to be safe and effective in this particular patient and the clinical improvement of disease resulted in an improved compliance to treatment.


The Evolution of Calcium-Based Signalling in Plants.
The calcium-based intracellular signalling system is used ubiquitously to couple extracellular stimuli to their characteristic intracellular responses. It is becoming clear from genomic and physiological investigations that while the basic elements in the toolkit are common between plants and animals, evolution has acted in such a way that, in plants, some components have diversified with respect to their animal counterparts, while others have either been lost or have never evolved in the plant lineages. In comparison with animals, in plants there appears to have been a loss of diversity in calcium-influx mechanisms at the plasma membrane. However, the evolution of the calcium-storing vacuole may provide plants with additional possibilities for regulating calcium influx into the cytosol. Among the proteins that are involved in sensing and responding to increases in calcium, plants possess specific decoder proteins that are absent from the animal lineage. In seeking to understand the selection pressures that shaped the plant calcium-signalling toolkit, we consider the evolution of fast electrical signalling. We also note that, in contrast to animals, plants apparently do not make extensive use of cyclic-nucleotide-based signalling. It is possible that reliance on a single intracellular second-messenger-based system, coupled with the requirement to adapt to changing environmental conditions, has helped to define the diversity of components found in the extant plant calcium-signalling toolkit.


Mechanisms of cysteine S-conjugate beta-lyases.
Mercapturic acids are conjugates of S-(N-acetyl)-L-cysteine formed during the detoxification of xenobiotics and during the metabolism of such endogenous agents as estrogens and leukotrienes. Many mercaturates are formed from the corresponding glutathione S-conjugates. This chapter focuses on (a) the discovery of the cysteine S-conjugate beta-lyases; (b) the involvement of pyridoxal-5-phosphate; (c) the influence of the electron-withdrawing properties of the group attached to the sulfur atom; and (d) the potential of cysteine S-conjugates as pro-drugs.


The complete mitochondrial genome of the wild silkworm moth, Actias selene.
The complete mitochondrial genome (mitogenome) of Actias selene (Lepidoptera: Saturniidae) was determined to be 15,236 bp, including 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes and a control region. The arrangement of 13 PCGs was similar to that of other sequenced lepidopterans. The AT skew of the mitogenome of A. selene was slightly negative, indicating a higher number of T compared to A nucleotides. The nucleotide composition of the mitogenome of A. selene was also biased toward A+T nucleotides (78.91%). All PCGs were initiated by ATN codons, except for the gene encoding cytochrome c oxidase subunit 1 (cox1), which may be initiated by the TTAG, as observed in other lepidopterans. Three genes, including cox1, cox2, and nad5, had incomplete stop codons consisting of just a T. With an exception for trnS1(AGN), all the other tRNA genes displayed a typical clover-leaf structure of mitochondrial tRNA. The A+T-rich region of the mitogenome of A. selene was 339 bp in length, and contains several features common to the Lepidopteras, including non-repetitive sequences, a conserved structure combining the motif ATAGA and an 18-bp poly-T stretch and a poly-A element upstream of trnM gene. Phylogenetic analysis showed that A. selene was close to Saturniidae.


Cognitive flexibility in children with Developmental Language Disorder: Drawing of nonexistent objects.
Cognitive flexibility is the ability to adapt thoughts and behaviors to new environments. Previous studies investigating cognitive flexibility in children with Developmental Language Disorder (DLD) present contradictory findings. In the current study, cognitive flexibility was assessed in 5- and 6-year-old preschoolers with DLD (n = 23) and peers with typical development (TD; n = 50) using a nonexistent object drawing (NEOD) task. The children were asked to draw a nonexistent man and a nonexistent house. The children with DLD did not differ from their peers with TD on simple category changes, which were comprised of changes in the size or shape of parts of the object, change of the whole shape of the object, and deletion of parts of the object. Nevertheless, children with DLD made fewer more complex, high-level category changes, which included same-category insertions, position exchange of object's parts, and cross-category insertions. The difference between DLD and TD on high-level category changes was related to differences between the two groups in verbal short-term memory and inhibition. Furthermore, children with DLD made no changes to their original drawings of an existing man and house more often than their peers with TD. It is concluded that children with DLD aged 5-6 years show less flexibility on the NEOD task than age-matched children with TD. This difference in cognitive flexibility may be related to lower levels of verbal short-term memory and inhibition ability of children with DLD, or to different use of these cognitive skills on the NEOD task.


[A preliminary study on the measurement of (1,3)-β-D-glucan in bronchoalveolar lavage for the diagnosis of pulmonary fungal infections].
To explore the measurement of (1,3)-β-D-glucan bronchoalveolar lavage fluid (BALF) for the diagnosis of pulmonary fungal infections. A total of 135 patients in the General Hospital of Tianjin Medical University from February 2010 to February 2011 were enrolled. There were 34 cases of confirmed or clinically diagnosed pulmonary fungal infections, 53 cases of bacterial pneumonia, and 48 cases of non-infection diseases. All patients underwent BAL and the BALF samples were obtained. (1,3)-β-D-glucan content (G test), in BALF and plasma were tested and the data were analyzed statistically by Mann-Whitney while the receiver operating characteristic curve (ROC curve) was established, from which the best threshold of the 2 G tests was derived. The median of BALF G test in the fungal infection group, pneumonia group and non-infection group was 281, 28 and 10 ng/L, respectively; the level in the fungal infection group being significantly higher than those of the other 2 groups (P < 0.001), but no significant difference being observed between the pneumonia group and the non-infection group (P > 0.05). The median of plasma G tests in the fungal infection group, the pneumonia group and the non-infection group was 27, 10, and 5 ng/L, respectively; the level in the fungal infection group being significantly higher than those in the other 2 groups (P < 0.001), but there was no significant difference between the pneumonia group and the non-infection group (P > 0.05). The best threshold of BALF G test was 67 ng/L, while the best threshold of G test of plasma was 17 ng/L. As compared to G test of plasma, G test of BALF may be more accurate, and have a higher clinical value for the earlier diagnosis of pulmonary fungal infections.


Outcome of stroke patients receiving different doses of recombinant tissue plasminogen activator.
Intravenous recombinant tissue plasminogen activator (tPA) at a dose of 0.9 mg/kg body weight is associated with a high hemorrhagic transformation (HT) rate. Low-dose tPA (0.6 mg/kg) may have a lower hemorrhage rate but the mortality and disability rates at 90 days cannot be confirmed as non-inferior to standard-dose tPA. Whether the doses 0.7 and 0.8 mg/kg have better efficacy and safety needs further investigation. Therefore, this study is to compare the efficacy and safety of each dose of tPA (0.6, 0.7, 0.8, and 0.9 mg/kg body weight) and to investigate the factors affecting early neurological improvement (ENI) and early neurological deterioration (END). For this observational study, data were obtained from 274 patients who received tPA thrombolytic therapy in Chia-Yi Christian Hospital stroke unit. The tPA dose was given at the discretion of each physician. The definition of ENI was a >8 point improvement (compared with baseline) at 24 h following thrombolytic therapy or an improvement in the National Institutes of Health Stroke Score (NIHSS) to 0 or 1 toward the end of tPA infusion. The definition of END was a >4 point increase in NIHSS (compared with baseline) within 24 h of tPA infusion. The primary objective was to investigate whether 0.7 and 0.8 mg/kg of tPA have higher ENI rate, lower END rate, and better outcome at 6 months. Poor outcome was defined as having a modified Rankin Scale of 3 to 6 (range, 0 [no symptoms] to 6 [death]). The secondary objective was to investigate whether low-dose tPA has a lower risk of intracerebral HT than that with standard-dose tPA. We also investigated the factors affecting ENI, END, HT, and 6-month outcome. A total of 274 patients were included during the study period, of whom 260 were followed up for >6 months. There was a trend for the HT rate to increase as the dose increased (P=0.02). The symptomatic HT rate was not significantly different among the low-dose and standard-dose groups. The ENI and END (P=0.52) were not significantly different among the four dosage groups. The clinical functional outcome at 6 months after stroke onset was poorer in the standard-dose group (P=0.02). Stroke severity (P<0.01), stroke type (P=0.03), and diabetes mellitus (P=0.04) affected the functional outcome at 6 months. Among the 274 patients receiving tPA thrombolytic therapy, the HT rate increased as dose increased. The symptomatic HT, ENI and END rates were not significantly different among the low-dose (0.6, 0.7, and 0.8 mg/kg) and standard-dose groups. Stroke severity (NIHSS >12), stroke type (cardioembolism and large artery atherosclerosis) and diabetes mellitus were associated with poor outcome at 6 months.


Residents should not independently perform focused abdominal sonography for trauma after 10 training examinations.
To assess whether 10 focused abdominal sonography for trauma (FAST) examinations could be used as a minimum standard for training, as suggested previously. This was a retrospective review of patients with abdominal trauma who underwent resident-performed FAST examinations before surgical or Department of Radiology evaluation. Six hundred ninety-eight patients were examined by resident-performed FAST followed by reference standard evaluations. Four hundred twelve patients were evaluated by residents who previously performed 10 FAST examinations; 154 were evaluated by 29 residents performing their 11th through 30th examinations; and 258 were evaluated by 10 residents performing their 31st and subsequent examinations. The results of resident-performed FAST for intraperitoneal free fluid were as follows: 11 to 20 examinations--sensitivity, 73.9% (95% confidence interval, 51.3%-88.9%); specificity, 98.8% (92.5%-99.9%); true-positive findings, 17; true-negative, 81; false-positive, 1; false-negative, 6; total patients, 105; 21 to 30 examinations--sensitivity, 100% (73.2%-100%); specificity, 97.1% (83.3%-99.9%); true-positive, 14; true-negative, 34; false-positive, 1; false-negative, 0; total patients, 49; 31 and more examinations--sensitivity, 94.8% (88.6%-97.9%); specificity, 98.6% (94.5%-99.8%); true-positive, 110; true-negative, 140; false-positive, 2; false-negative, 6; total patients, 258. The suggestion that 10 examinations could be used as a minimum standard for training in FAST examinations was not validated.


Phage typing and PFGE pattern analysis as tools for epidemiological surveillance of Salmonella enterica serovar Bovismorbificans infections.
Some years ago, an increase in the number of sporadic cases and outbreaks of salmonellosis due to S. enterica serovar Bovismorbificans was observed in several European countries including Finland, Sweden, England/Wales, Austria, and Germany. In order to understand the recent spread of this serovar and to trace the route of infection back to its source, it was considered necessary to subtype S. Bovismorbificans isolates. Using phage typing (newly described here) and molecular fingerprinting (PFGE-pattern, plasmid profiles and ribotype) the isolates of European origin could be subtyped and compared to S. Bovismorbificans isolates that originated in overseas countries such as Australia, Thailand, India, etc. where this serovar was isolated more frequently. Significant clonal diversity was identified but some of the clonal types of S. Bovismorbificans dominated the epidemics and single cases in Europe as well as in overseas countries. The clonal identity among these isolates indicates an international distribution, new sources of infection, and highlights the urgent requirement for standardized laboratory based surveillance networks (e.g. Enter-Net). Moreover, it is suggested that strains of S. Bovismorbificans will continue to be of concern in public health and that phage typing together with PFGE typing can be applied as reliable and rapid tools for their future monitoring.


Extrahepatic manifestations associated with chronic hepatitis C infections in Poland.
To assess the prevalence and predictive factors of extrahepatic manifestation (EM) in patients with chronic hepatitis C (CHC) infection in Poland. 340 consecutive patients (mean age: 42 years) with untreated CHC were studied between 2000 and 2006. The HCV infection was defined by positive serology and serum HCV RNA. The inflammation grade and fibrosis stage were assessed according to Ishak. Demographic, laboratory and liver biopsy data were collected. The patients with liver cirrhosis, concomitant HBV or HIV infection, autoimmune liver diseases and alcohol abusers were excluded from the analysis. 210 patients with CHC (61.7%) presented at least 1 extrahepatic manifestation, including mixed cryoglobulinemia (37.1%), thrombocytopenia (27.6%), thyroid autoimmunity (16.2%), dermatological disorders (4.1%) and type 2 diabetes (4.1%). Other EM such as the sicca syndrome, nephropathy, polyneuropathy and B-cell lymphoma were observed in single cases. In multivariate analysis lower platelet count was found as a predictive factor of EM in patients with CHC. The majority of patients with CHC, living in Poland, have EM, of which cryoglobulinemia, thrombocytopenia, thyroid autoimmunity, dermatological disorders and type 2 diabetes are most common. Through the multivariate analysis the lower platelet predicts extrahepatic manifestations associated with chronic hepatitis C.


PTEN signaling through RAF1 proto-oncogene serine/threonine kinase (RAF1)/ERK in the epididymis is essential for male fertility.
Without a fully developed initial segment, the most proximal region of the epididymis, male infertility results. Therefore, it is important to understand the development and regulation of this crucial region. In addition to distinctively high activity levels of the components of the ERK pathway, which are essential for initial-segment differentiation, the initial segment exhibits high protein and activity levels of phosphatase and tensin homolog (PTEN). To understand the role of PTEN in the regulation of the initial segment, we generated a mouse model with a conditional deletion of Pten from the epithelial cells of the proximal epididymis from postnatal day 17 (P17) onward. Shortly after Pten deletion, hypertrophy of the proximal epididymis became evident. Loss of Pten resulted in activation of the AKT (protein kinase B) pathway components from P28 onward, which in turn gradually suppressed RAF1 proto-oncogene serine/threonine kinase (RAF1)/ERK signaling through the interaction between AKT and RAF1. Consistent with progressive changes in RAF1/ERK signaling, loss of Pten progressively altered cell shape, size, organization, proliferation, and survival in the initial-segment epithelium and resulted in dedifferentiation and extensive epithelial folding. Most importantly, knockout males progressively lost fertility and became infertile from 6 to 12 mo. Spermatozoa from older knockout mice showed a lower percentage of motility and a higher percentage of flagellar angulation compared with controls, suggesting compromised sperm maturation. Therefore, under normal physiological conditions, PTEN suppresses AKT activity to maintain activation of the RAF1/ERK signaling pathway, which in turn maintains normal function of the initial segment and therefore, normal sperm maturation.


Presentation of a functional pituitary adenoma as a significant decrease in prostate-specific antigen level in a patient followed for prostate cancer.
The stimulatory role of testosterone in the production and release of prostate-specific antigen (PSA) has been well characterized. Testosterone production by the testes is dependent on a functional hypothalamic-pituitary-gonadal axis. High prolactin levels have been shown to disrupt this axis, resulting in decreases in gonadotropins and testosterone levels. We report a patient with prostate cancer and elevated PSA levels followed with "watchful waiting" for several years who experienced a precipitous decrease in PSA level over a 3 month period. The patient was found to have an asymptomatic prolactin-secreting pituitary macroadenoma.


Insight into the function of active site residues in the catalytic mechanism of human ferrochelatase.
Ferrochelatase catalyzes the insertion of ferrous iron into a porphyrin macrocycle to produce the essential cofactor, heme. In humans this enzyme not only catalyzes the terminal step, but also serves a regulatory step in the heme synthesis pathway. Over a dozen crystal structures of human ferrochelatase have been solved and many variants have been characterized kinetically. In addition, hydrogen deuterium exchange, resonance Raman, molecular dynamics, and high level quantum mechanic studies have added to our understanding of the catalytic cycle of the enzyme. However, an understanding of how the metal ion is delivered and the specific role that active site residues play in catalysis remain open questions. Data are consistent with metal binding and insertion occurring from the side opposite from where pyrrole proton abstraction takes place. To better understand iron delivery and binding as well as the role of conserved residues in the active site, we have constructed and characterized a series of enzyme variants. Crystallographic studies as well as rescue and kinetic analysis of variants were performed. Data from these studies are consistent with the M76 residue playing a role in active site metal binding and formation of a weak iron protein ligand being necessary for product release. Additionally, structural data support a role for E343 in proton abstraction and product release in coordination with a peptide loop composed of Q302, S303 and K304 that act a metal sensor.


The prognostic value of multidetector coronary CT angiography for the prediction of major adverse cardiovascular events: a multicenter observational cohort study.
To assess the prognostic value of coronary artery stenosis identification by coronary computed tomographic angiography (CCTA) for the prediction of major adverse cardiac events (MACE) in a multicenter prospective cohort study. We performed a prospective multicenter observational cohort study of symptomatic patients with suspected or known coronary artery disease (CAD) (n = 172; 57% male) undergoing CCTA in accordance to ACC/AHA Appropriateness Criteria from 4 sites in and around Paris, France, and followed for a mean duration of 22.0 +/- 4.5 months (interquartile range 18-26 months). Coronary arteries by CCTA were interpreted by physicians blinded to the patient characteristics for the presence or absence obstructive (>or=70% luminal diameter stenosis), as well as for plaque composition categorized as non-calcified, calcified or "mixed." MACE was defined as death, non-fatal myocardial infarction, unstable angina or target vessel revascularization. MACE event rates were compared between patients with or without obstructive plaque and with differing plaque compositions. MACE event rates were significantly higher in patients with obstructive coronary artery stenosis by CCTA compared to those without (61.1% vs. 3.9%, P < 0.01). In patients with obstructive stenosis, mixed (83.3% vs. 25.3%, P < 0.01) and calcified (94.4% vs. 50.7%, P < 0.01) plaque presence was significantly higher than in patients without obstructive stenosis, with no differences in prevalence of non-calcified plaque (27.8% vs. 20.8%, P = NS). For MACE, the negative predictive value of no observed coronary artery plaque was 100% in the follow-up period. In this prospective multicenter study of symptomatic patients with suspected or known CAD undergoing CCTAs interpreted by imagers blinded to patient characteristics, CCTA presence of plaque severity and composition successfully identifies patients at risk for incident MACE events. Importantly, a negative CCTA portends an extremely low risk for incidence MACE.


Subchondral microfracture of the knee without osteonecrosis after arthroscopic medial meniscectomy.
We report a case of an osteonecrosis-like lesion of the knee that developed shortly after an arthroscopic medial meniscectomy. Clinical presentation, physical findings, and imaging of the knee including magnetic resonance imaging were similar to those of the cases that have been reported as osteonecrosis after meniscectomy. However, histologic analysis of the lesion revealed that there was no osteonecrosis but rather a subchondral microfracture with active callus formation.


Self-harm in pregnancy and the postnatal year: prevalence and risk factors.
Self-harm in pregnancy or the year after birth ('perinatal self-harm') is clinically important, yet prevalence rates, temporal trends and risk factors are unclear. A cohort study of 679 881 mothers (1 172 191 pregnancies) was conducted using Danish population register data-linkage. Hospital treatment for self-harm during pregnancy and the postnatal period (12 months after live delivery) were primary outcomes. Prevalence rates 1997-2015, in women with and without psychiatric history, were calculated. Cox regression was used to identify risk factors. Prevalence rates of self-harm were, in pregnancy, 32.2 (95% CI 28.9-35.4)/100 000 deliveries and, postnatally, 63.3 (95% CI 58.8-67.9)/100 000 deliveries. Prevalence rates of perinatal self-harm in women without a psychiatric history remained stable but declined among women with a psychiatric history. Risk factors for perinatal self-harm: younger age, non-Danish birth, prior self-harm, psychiatric history and parental psychiatric history. Additional risk factors for postnatal self-harm: multiparity and preterm birth. Of psychiatric conditions, personality disorder was most strongly associated with pregnancy self-harm (aHR 3.15, 95% CI 1.68-5.89); psychosis was most strongly associated with postnatal self-harm (aHR 6.36, 95% CI 4.30-9.41). For psychiatric disorders, aHRs were higher postnatally, particularly for psychotic and mood disorders. Perinatal self-harm is more common in women with pre-existing psychiatric history and declined between 1997 and 2015, although not among women without pre-existing history. Our results suggest it may be a consequence of adversity and psychopathology, so preventative intervention research should consider both social and psychological determinants among women with and without psychiatric history.


Psychoanalysis as therapeutic crisis induction. Affect and emotion as a prerequisite of radical change.
Far beyond psychoanalysis and the 20th century there is a very long tradition of the idea that under normal circumstances our convictions, values, attitudes and behaviour patterns are a more or less consistent system, not to be radically changed, unless a shaking-up happens, which reduces confidence into this value system. Only then would an intensive search for new and better possibilities of adaption to reality occur. In this paper, four theses on the problem of psychoanalytic crisis induction will first be presented. Thereafter, the phase of crisis induction within psychoanalytic therapy will be described in terms of Janzarik's concept of structural-dynamic coherence. Finally, a comparison between different forms of crisis induction such as psychoanalysis, group dynamics and trauma shall stress the ethical aspects of the matter.


Breeding on the leading edge of a northward range expansion: differences in morphology and the stress response in the arctic Gambel's white-crowned sparrow.
Individuals at the forefront of a range shift are likely to exhibit phenotypic traits that distinguish them from the population breeding within the historic range. Recent studies have examined morphological, physiological and behavioral phenotypes of individuals at the edge of their range. Several studies have found differences in the hypothalamic-pituitary-adrenal (HPA) axis activity in response to acute restraint stress in individuals at the range limits. HPA axis activation leads to elevations in glucocorticoids that regulate physiology and behavior. Here we compare the hormonal profiles and morphometrics from Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) breeding at the northern limit of the population's range to those birds breeding within the historic population range. Birds breeding at the northern limit experienced a harsher environment with colder temperatures; however, we found no differences in arthropod prey biomass between the northern limit and more southern (historic) sites. Males at the northern limit had higher body condition scores (mass corrected for body size) compared to individuals within the historic range, but no differences were found in beak and tarsus lengths, wing chord, muscle profile or fat stores. In males during the pre-parental stage, before breeding commenced, HPA axis activity was elevated in birds at the northern limit of the range, but no differences were found during the parental or molt stages. Females showed no differences in HPA axis activity during the parental stage. This study suggests that "pioneering" individuals at the limits of their breeding range exhibit physiology and morphology that are distinct from individuals within the historic range.


[PHA- and PWM-stimulation in acute leukaemia (author's transl)].
Peripheral blood cells from patients with acute leukaemia were stimulated in RPMI-medium with Phytohaemagglutinin (PHA) and/or Pokeweed-Mitogen (PWM). Samples of the cultures were taken at 3, 5 and 7 day intervals for cytological characterization. From 119 cultures from 65 patients 76 cultures from 47 patients could be analysed. Cultures stimulated with PHA and/or PWM showed in 43,4% a higher stimulation rate in comparison with cultures from normal persons. These findings are discussed in relation to the increased agar-colony growth growth of leukaemic cells after in vitro PHA-stimulation and transformation of blast cells.


Application of a stool antigen test to evaluate the incidence of Helicobacter pylori infection in children and adolescents from Tehran, Iran.
Helicobacter pylori infection is acquired mainly in childhood, especially in developing countries, where a low-cost, rapid diagnostic technique which is reliable for all age groups may be useful for the management of H. pylori infection. For this purpose, we used an HpSA test (Equipar) to detect H. pylori infection in children and adolescents from Tehran, Iran. Thirty-five children who were positive or negative for H. pylori infection by endoscopy-based tests were used as positive and negative controls for the HpSA test. Stools were collected from 430 randomly selected children and adolescents (4 to 18 years old) from southwest, near the center, and northwest of Tehran. A questionnaire that included presence of recurrent abdominal pain (RAP), family history of infection and/or peptic ulcer disease (PUD), and income of parents was completed. A good agreement was found between the results of endoscopy-based tests and those of the HpSA test; the sensitivity and specificity of the Equipar-HpSA test were 100% and 83.4%, respectively. Among 430 children and adolescents, 47% were positive by the HpSA test, of whom 82% had RAP. No difference in incidence was observed between the two sexes; the various categories of age showed an increasing incidence, ranging from 24% (ages 4 to 6) to 58% (ages 16 to 18). The rate of infection in children and adolescents from the southwest was significantly higher (70%) than the rate in those from the northwest (32%), and a family history of H. pylori infection or PUD was observed in 59% of the HpSA positive subjects. The HpSA test is a useful test to detect H. pylori infection in children and adolescents from developing countries.


Effects of antidepressant drugs on the activity of cytochrome P-450 measured by caffeine oxidation in rat liver microsomes.
Caffeine is a marker drug for testing the activity of CYP1A2 (3-N-demethylation) in humans and rats. Moreover, it is also a relatively specific substrate of CYP3A (8-hydroxylation). In the case of 1-N- and in particular 7-N-demethylation of caffeine, apart from CYP1A2, other cytochrome P-450 isoenzymes play a considerable role. The aim of the present study was to investigate the influence of imipramine, amitriptyline and fluoxetine on cytochrome P-450 activity measured by caffeine oxidation in rat liver microsomes. The obtained results showed that imipramine exerted a most potent inhibitory effect on caffeine metabolism. Imipramine decreased the rate of 3-N-, 1-N- and 7-N-demethylations, and 8-hydroxylation of caffeine, the effect on 3-N-demethylation being most pronounced (Ki = 33 microM). Amitriptyline showed distinct inhibition of 3-N- and 1-N-demethylation of caffeine, though its effect was less potent than in the case of imipramine (Ki = 57 and 61 pM, respectively). The influence of amitriptyline on 8-hydroxylation and especially on 7-N-demethylation of caffeine was weaker (Ki = 108 and 190 pM, respectively) than on 3-N- or 1-N-demethylation, suggesting a narrower spectrum of cytochrome P-450 inhibition by amitriptyline than by imipramine, involving mainly the subfamily CYP1A2, and--to a lesser degree--CYP3A. In contrast to the tested tricyclic antidepressants, fluoxetine did not exert any considerable effect on the 3-N- or 1-N-demethylation of caffeine (Ki = 152 and 196 microM, respectively), which indicates its low affinity for CYP1A2. However, fluoxetine displayed a clear inhibitory effect on caffeine 7-N-demethylation (Ki = 72 microM), the reaction which is catalyzed mainly by other than CYP1A2 isoenzymes. Fluoxetine diminished markedly the 8-hydroxylation of the marker drug; as reflected by Ki values, the potency of inhibition of rat CYP3A by fluoxetine was similar to that of imipramine (Ki = 40 and 45 microM, respectively). In summary, CYP1A2 was distinctly inhibited by imipramine and amitriptyline, CYP3A by imipramine and fluoxetine, while other CYP isoenzymes (CYP2B and/or 2E1) by imipramine and fluoxetine.


Role of the serotonin 5-HT(2A) receptor in learning.
This study reviews the role of the serotonin 5-HT2A receptor in learning as measured by the acquisition of the rabbit's classically conditioning nictitating membrane response, a component of the eyeblink response. Agonists at the 5-HT2A receptor including LSD (d-lysergic acid diethylamide) enhanced associative learning at doses that produce cognitive effects in humans. Some antagonists such as BOL (d-bromolysergic acid diethylamide), LY53,857, and ketanserin acted as neutral antagonists in that they had no effect on learning, whereas others (MDL11,939, ritanserin, and mianserin) acted as inverse agonists in that they retarded learning through an action at the 5-HT2A receptor. These results were placed in the context of what is known concerning the anatomical distribution and electrophysiological effects of 5-HT2A receptor activation in frontal cortex and hippocampus, as well as the role of cortical 5-HT2A receptors in schizophrenia. It was concluded that the 5-HT2A receptor demonstrates constitutive activity, and that variations in this activity can produce profound alterations in cognitive states.


Orbital-optimized MP2.5 and its analytic gradients: approaching CCSD(T) quality for noncovalent interactions.
Orbital-optimized MP2.5 [or simply "optimized MP2.5," OMP2.5, for short] and its analytic energy gradients are presented. The cost of the presented method is as much as that of coupled-cluster singles and doubles (CCSD) [O(N(6)) scaling] for energy computations. However, for analytic gradient computations the OMP2.5 method is only half as expensive as CCSD because there is no need to solve λ2-amplitude equations for OMP2.5. The performance of the OMP2.5 method is compared with that of the standard second-order Møller-Plesset perturbation theory (MP2), MP2.5, CCSD, and coupled-cluster singles and doubles with perturbative triples (CCSD(T)) methods for equilibrium geometries, hydrogen transfer reactions between radicals, and noncovalent interactions. For bond lengths of both closed and open-shell molecules, the OMP2.5 method improves upon MP2.5 and CCSD by 38%-43% and 31%-28%, respectively, with Dunning's cc-pCVQZ basis set. For complete basis set (CBS) predictions of hydrogen transfer reaction energies, the OMP2.5 method exhibits a substantially better performance than MP2.5, providing a mean absolute error of 1.1 kcal mol(-1), which is more than 10 times lower than that of MP2.5 (11.8 kcal mol(-1)), and comparing to MP2 (14.6 kcal mol(-1)) there is a more than 12-fold reduction in errors. For noncovalent interaction energies (at CBS limits), the OMP2.5 method maintains the very good performance of MP2.5 for closed-shell systems, and for open-shell systems it significantly outperforms MP2.5 and CCSD, and approaches CCSD(T) quality. The MP2.5 errors decrease by a factor of 5 when the optimized orbitals are used for open-shell noncovalent interactions, and comparing to CCSD there is a more than 3-fold reduction in errors. Overall, the present application results indicate that the OMP2.5 method is very promising for open-shell noncovalent interactions and other chemical systems with difficult electronic structures.


Prediction and validation of total and regional skeletal muscle mass by ultrasound in Japanese adults.
The present study was performed to develop regression-based prediction equations for skeletal muscle (SM) mass by ultrasound and to investigate the validity of these equations in Japanese adults. Seventy-two Japanese men (n=38) and women (n=34) aged 18-61 years participated in this study and were randomly separated into two groups: the model development group (n=48) and the validation group (n=24). The total and regional SM mass were measured using magnetic resonance imaging (MRI) 1.5 T-scanners with spin-echo sequence. Contiguous transverse images (about 150 slices) with a slice thickness of 1 cm were obtained from the first cervical vertebra to the ankle joints. The volume of SM was calculated from the summation of digitized cross-sectional area. The SM volume was converted into mass units (kg) by an assumed SM density of 1.04 kg l(-1). The muscle thickness (MTH) was measured by B-mode ultrasound (5 MHz scanning head) at nine sites on the anatomical SM belly. Strong correlations were observed between the site-matched SM mass (total, arm, trunk body, thigh, and lower leg) by MRI measurement and the MTH x height (in m) in the model development group (r=0.83-0.96 in men, r=0.53-0.91 in women, P<0.05). When the SM mass prediction equations were applied to the validation group, significant correlations were also observed between the MRI-measured and predicted SM mass (P<0.05). The predicted total SM mass for the validation group was 19.6 (6.5) kg and was not significantly different from the MRI-measured SM mass of 20.2 (6.5) kg. Bland-Altman analysis did not indicate a bias in prediction of the total SM mass for the validation group (r=0.00, NS). These results suggested that ultrasound-derived prediction equations are a valid method to predict SM mass and an alternative to MRI measurement in healthy Japanese adults.


Remodeling of the rat saphenous vein network in response to long-term gravitational load.
Our main objective was to test whether chronic orthostatic body position induces network changes in the saphenous vein superficial tributary system of the rat. Fourteen male Sprague-Dawley rats were kept in tilted tube cages (45-degree head-up position) for two weeks to induce chronic gravitational load to their leg veins. Ten animals housed in normal cages and four animals kept in horizontally positioned tube cages served as controls. The whole superficial network of the left saphenous vein was microprepared surgically under anesthesia, superfused with saline and observed under a videomicroscope, while normal flow and pressure were maintained in the lumen. Branching angles, lengths of venous segments and their diameters were measured offline from digitized images using special image-analyzing software. Several branching angles at the popliteal confluence were significantly reduced by 12.5-15.8 %. The in vivo diameter of the main branch (936+/-34 vs. 805+/-44 microm) and of one of the popliteal tributaries (776+/-38 vs. 635+/-36 microm) increased (p<0.05), comparing vessels from tilted animals with those from normal controls. Maintaining the animals in horizontal tube cages did not induce the above alterations. The increased diameters and reduced branching angles of the saphenous vein network observed are adaptive responses of the venous network to a long-term gravitational load.


Predictors of Satisfaction and Value of Advanced Training for Mental Health Professionals in Wartime Ukraine.
The full-scale escalation of Russia's war against Ukraine in 2022 created a surge of mental health issues, requiring urgent, evidence-based interventions to reduce trauma and mitigate stress. Reflecting recommendations from leading specialists in the field, Ukrainian mental health professionals sought to develop appropriate skills and knowledge for working in wartime through advanced training programs. This study aimed to investigate the experiences of Ukrainian mental health professionals having completed advanced training in mental health topics in wartime. A survey design was adopted, using the purposefully developed, and validated 'Wartime Learning Satisfaction Scale'. Regression analysis assessed the hypothesized contribution of four scales (Education, Educator, Learner, and War) to the perceived value of advanced training and learners' satisfaction. Respondents (n = 271) were trained in up to 30 courses (M = 4.27, SD = 3.03) lasting from two to over 120 h. Regression analysis revealed different predictors for satisfaction and value of the courses. Advanced training resulted in higher satisfaction with learning if it matched professional goals of mental health professionals and perceived higher value when relevant to societal demand, consistently constructed, practically useful, and not solely focusing on war-related issues. Respondents who completed all advanced training courses they were interested demonstrated significantly higher confidence in working in wartime. These findings are essential for effective mental health practice during wartime.


Technology Addiction among Treatment Seekers for Psychological Problems: Implication for Screening in Mental Health Setting.
Technology usage has seen an increase among users. The usage varies from social, personal, and psychological reasons. Users are frequently using to overcome mood states as well as to manage the other psychological states. This work is going to explore the information technology use among subjects with a psychiatric disorder. A total of 75 subjects were assessed using background data sheet, internet addiction impairment index, video game use pattern, pornography addiction screening tool and screening for mobile phone use, from in-patient and out-patient setting of tertiary mental health setting. It showed the presence of addiction to mobile, internet, video game, and pornography. Age was found to be negatively correlated with this addiction. Average usage time had been associated with management of mood states. The addiction to information technology had been associated with a delay in initiation of sleep. This work has implication for screening technology addiction among subjects seeking treatment for psychological problems and motivate them to develop the healthy use of technology.


Self-cleavage activity of the genomic HDV ribozyme in the presence of various divalent metal ions.
To identify the divalent metal ions that can support the self-cleavage activity of the genomic ribozyme of human hepatitis delta virus (HDV), we tested the activity of various divalent metal ions in the ribozyme reactions catalyzed by HDV88 (683-770 nt) and 88DI3 (HDV88 with the sequence from 740-752 nt deleted). Among various metal ions tested, Mg2+, Mn2+, Ca2+ and Sr2+ efficiently supported the self-cleavage reactions of the HDV88 and 88DI3 ribozymes. In the case of the 88DI3 ribozyme, other divalent metal ions, such as Cd2+, Ba2+, Co2+, Pb2+ and Zn2+, were also able to support the self-cleavage reaction to some extent (< 10%). In the presence of spermidine (0.5 mM), the cleavage reaction was promoted at lower concentrations of effective divalent metal ions. The HDV ribozyme represents the only example of ribozyme to date of a ribozyme that catalyzes the self-cleavage reaction in the presence of Ca2+ ions as efficiently as it does in the presence of Mg2+ ions.


Two decades of imipenem therapy.
Imipenem, the first carbapenem discovered, was developed more than two decades ago in response to an unmet need for a highly potent, broad-spectrum antimicrobial agent with a strong safety profile. It has since been used to treat more than 26 million patients. In an era where antibiotic use has driven antibiotic resistance, choosing appropriate initial therapy for serious infection is critical. Appropriate antibiotic regimens must cover all likely pathogens, be administered promptly at the correct dosage and dosing interval, be well tolerated and prevent the emergence of resistance. While imipenem was initially reserved for use in intractable, serious infections, the benefits of early aggressive therapy are now known, making imipenem a core agent in de-escalation therapy due to proven efficacy and safety for indications such as nosocomial pneumonia, intra-abdominal infection, sepsis and febrile neutropenia. De-escalation therapy with an agent such as imipenem minimizes resistance development by initiating aggressive initial treatment and then tailoring therapy based on patient response and culture results, switching to a less expensive, narrower spectrum antibiotic regimen or shortening the duration of therapy. Imipenem has maintained sustained clinical efficacy, tolerability and in vitro activity against important bacterial pathogens for two decades. We review the factors that continue to make imipenem as appropriate an agent for de-escalation therapy now as it was 20 years ago.


TNF-alpha inhibits isoproterenol-stimulated adenylyl cyclase activity in cultured airway smooth muscle cells.
Inflammation, increased cytokine production, and decreased responsiveness of airway smooth muscle (ASM) to beta-adrenergic agonists are characteristics of asthma. We questioned whether the cytokine tumor necrosis factor-alpha (TNF-alpha) directly impaired beta-adrenergic signal transduction in cultured canine ASM cells. Confluent ASM cells exposed to TNF-alpha (0.1-10 ng/ml) for 72 h showed lower maximal levels of adenylyl cyclase activity in response to isoproterenol (10 ng/ml; 14 +/- 4.3 vs. 7.5 +/- 1.3 pmol adenosine 3',5'-cyclic monophosphate x well(-1) x 20 min(-1), control vs. treated, respectively), despite no changes in beta-adrenergic receptor numbers (maximum number of binding sites = 4.8 +/- 0.72 vs. 4.5 +/- 0.81 fmol/mg protein, control vs. treated, respectively). Adenylyl cyclase activities in response to prostaglandin E1, NaF, or forskolin were not different in treated and untreated cells. These results demonstrate that a cytokine known to be increased during exacerbation of asthmatic symptoms directly impairs beta-adrenergic function in ASM cells and suggests a mechanism by which inflammation impairs beta-adrenergic receptor signal transduction in asthma.


Average current mode controller for bridgeless PFC SEPIC converter with second-order model reduction operated in continuous conduction mode.
This paper proposes an average current mode controller (ACMC) for a single-phase bridgeless power factor correction (PFC) circuit using a single ended primary inductor converter (SEPIC) via second-order model reduction. The superiority of the proposed controller is PFC accomplished at power up to 350 W with high efficiency via the second-order model reduction. The design and implementation of ACMC on the converter operated with continuous conduction mode (CCM) is explained in detail. ACMC forces input current to follow sinusoidal current reference at different power levels and sustain high power factor (PF). The proposed controller is designed based on the theoretical analysis operation of the circuit. For verification, MATLAB/Simulink simulations are carried out and validation through an experiment test rig for 110-220 Vrms input, 100 Vdc/ 350 W output prototype at 20 kHz switching frequency. It is proven that the proposed controller strategy accomplishes high PF, high efficiency and conformity with the simulation.


Cannabinoid receptor 2 (CB2) agonists and L-arginine ameliorate diabetic nephropathy in rats by suppressing inflammation and fibrosis through NF-κβ pathway.
Diabetic nephropathy (DN) is a condition that leads to end-stage chronic kidney disease characterized by inflammation and a deficiency of nitric oxide (NO). Cannabinoid receptor (CB2) activation by specific agonist reduces nuclear factor kappa beta (NF-κβ) expression. Beta caryophyllene (BCP), a natural CB2 receptor activator, protects kidney function in several diseases. L-Arginine (LA) modulates several physiological processes by donating nitric oxide (NO). Hence, we tested a novel BCP-LA combination to treat DN and investigated its molecular mechanisms. BCP, LA, and combinations of both were evaluated in LPS-induced RAW 264.7 macrophage inflammation as well as in streptozotocin (55 mg/kg)-induced diabetes in SD rats. Diabetic rats were administered 200 mg/kg of BCP, 100 mg/kg of LA, and combination of both orally for 28 days. Biochemical markers and inflammatory cytokines were assessed in plasma; also, kidney tissue was examined for renal oxidative stress injury, NF-κβ expression, and histology. After 28 days of treatment, BCP and LA combination significantly lowered plasma glucose levels than the disease control group. BCP and LA also normalized renal markers and oxidative stress of diabetic rats. Plasma and RAW macrophage cell lines showed reduced levels of IL-6 and TNF-α (P < 0.001). Histopathological evaluations revealed that BCP and LA together decreased renal fibrosis and collagen deposition also improved nephrotic indices. Meanwhile, the effect of BCP and LA together significantly reduced the NF-κβ (P < 0.01) against diabetic rats. These results indicate that the innovative regimen BCP with LA may be a therapeutic treatment for DN, as it protects kidney tissue from diabetes via NF-κβ inhibition.


Topic manipulation and cohesive adequacy in conversations of normal adults between the ages of 30 and 90.
Few investigations have studied changes in normal conversational performance throughout the lifespan. The present study gathered preliminary data on 40 normal-language subjects between the ages of 30 and 90 years. The subjects were matched for age and sex in dyads and engaged in conversations. The conversations were analyzed for topic manipulation skills (introduction, reintroduction, maintenance, shading) and cohesive adequacy (complete ties, erroneous ties, incomplete ties). Significant differences were found between older and younger dyads on the topic and cohesion variables.


Isolation, virtual screening, action mechanisms, chelation with zinc ions, and stability of ACE-inhibitory peptides from ginkgo seed globulin.
Ginkgo seed has potential applications in the prevention and treatment of hypertension, but its application in food is limited. Thus, ginkgo seed globulin was hydrolyzed using dual enzymes (Alcalase and thermolysin). After gel column separation, reverse-phase high-performance liquid chromatographic purification, and ESI-MS/MS analysis, five oligopeptides containing fewer than 12 amino acid residues were obtained. Among them, the heptapeptide Glu-Ala-Ser-Pro-Lys-Pro-Val (EASPKPV) offered relatively high capacities to inhibit ACE (IC50: 87.66 μmol L-1) and bind with zinc ions (5.35 ± 0.32 mg g-1). Moreover, EASPKPV showed competitive inhibitory kinetics against ACE. Fourier-transform infrared spectroscopy analysis evidenced that the amino group and carboxyl group of EASPKPV could both provide binding sites for zinc ions. EASPKPV can restrain ACE in the following ways: (i) competitively linking with five key residues (Gln281, Ala354, Glu376, Lys511, and Tyr523) in the S1 and S2 pockets of ACE by short hydrogen bonds; (ii) binding to thirteen active residues of ACE via hydrophobic interactions; and (iii) binding with residue His383 or the zinc ion of zinc tetrahedral coordination. Additionally, simulated gastrointestinal digestion did not show any remarkable efficacy on the capacities of EASPKPV to restrain ACE and bind with zinc ions. These results indicate that ginkgo peptides may be used for antihypertension.


Scribble1 plays an important role in the pathogenesis of neural tube defects through its mediating effect of Par-3 and Vangl1/2 localization.
Scribble1 (Scrib1) is a tumor suppressor gene that has long been established as an essential component of apicobasal polarity (ABP). In mouse models, mutations in Scrib1 cause a severe form of neural tube defects (NTDs) as a result of a defective planar cell polarity (PCP) signaling. In this study, we dissected the role of Scrib1 in the pathogenesis of NTDs in its mouse mutant Circletail (Crc), in cell lines and in a human NTD cohort. While there were no obvious defects in ABP in the Scrib1Crc/Crc neuroepihelial cells, we identified an abnormal localization of the apical protein Par-3 and of the PCP protein Vangl2. These results were concordant with those obtained following a partial knockdown of Scrib1 in MDCK II cells. Par-3 was able to rescue the localization defect of Vangl1 (paralog of Vangl2) caused by partial knockdown of Scrib1 suggesting that Scrib1 exerts its effect on Vangl1 localization indirectly through Par-3. This conclusion is supported by our findings of an apical enrichment of Vangl1 following a partial knockdown of Par-3. Re-sequencing analysis of SCRIB1 in 473 NTD patients led to the identification of 5 rare heterozygous missense mutations that were predicted to be pathogenic. Two of these mutations, p.Gly263Ser and p.Gln808His, and 2 mouse NTD mutations, p.Ile285Lys and p.Glu814Gly, affected Scrib1 membrane localization and its modulating role of Par-3 and Vangl1 localization. Our study demonstrates an important role of Scrib1 in the pathogenesis of NTDs through its mediating effect of Par-3 and Vangl1/2 localization and most likely independently of ABP.


Role of proinflammatory cytokines in the impaired lacrimation associated with autoimmune xerophthalmia.
To determine the effects of the proinflammatory cytokines interleukin (IL)-1alpha, IL-1beta, and tumor necrosis factor (TNF)-alpha on neurally mediated lacrimal gland protein secretion and to determine whether the amount of IL-1beta protein is upregulated in inflamed lacrimal glands of the MRL/lpr mouse, a murine model of human Sjögren syndrome. Lacrimal gland lobules of BALB/c mice were prepared and incubated for 2 hours in the presence or absence of recombinant human (rh)IL-1alpha, rhIL-1beta (10 ng/mL each), or rhTNFalpha (50 ng/mL). Peroxidase secretion in response to depolarizing KCl (75 mM) solution was measured by spectrofluorometric assay. In another set of experiments, saline, rhIL-1beta (1 microg), or an antibody against IL-1 receptor type I (IL-1RI), with or without rhIL-1beta, was injected (2 microL) into the lacrimal glands of anesthetized BALB/c mice. Twenty-four hours later, lacrimal gland lobules were prepared and peroxidase secretion was measured. The amount of IL-1beta protein in lacrimal gland acinar cell lysates prepared from 3-, 9-, and 13-week-old BALB/c, MRL/(+), and MRL/lpr mice was determined by ELISA. KCl-induced peroxidase secretion was inhibited in vitro 62%, 66%, and 53% by rhIL-1alpha, rhIL-1beta, and rhTNFalpha, respectively. In vivo, rhIL-1beta inhibited KCl-induced peroxidase secretion by 72%. This inhibitory effect of IL-1beta was completely reversed by an antibody against IL-1RI. Compared with 3-week-old mice, the amount of IL-1beta protein was upregulated 15- and 21-fold in lacrimal gland acinar cells isolated from 9- and 13-week-old MRL/lpr mice, respectively. Proinflammatory cytokines inhibit neurally mediated lacrimal gland secretion. The amount of IL-1beta protein is upregulated in acinar cells prepared from lacrimal glands infiltrated with lymphocytes. These results suggest that elevated levels of IL-1beta, as they occur in Sjögren syndrome exocrine glands, may impair the secretory function of these tissues.


Desensitization: effects on cutaneous and peritoneal manifestations of delayed hypersensitivity in relation to lymphokine production.
Guinea pigs exhibiting delayed hypersensitivity may be desensitized by a single large dose of antigen administered intramuscularly. In the present experiments, desensitization with a soluble protein such as egg albumin (EA) or bovine gamma-globulin (BGG) was nonspecific in that they suppressed both cutaneous reactivity and the macrophage disappearance reaction (MDR) to unrelated antigen in doubly immunized animals. In contrast, myobacterial antigen, at the dose studied, showed limited specificity in that it could suppress the MDR but not a skin test to an unrelated antigen. Induction of an MDR was shown to be associated with the appearance of macrophage migration inhibitory factor (MIF) and chemotactic activity in the peritoneal exudate fluid. Pretreatment with desensitizing doses of mycobacteria prevented the EA-induced appearance of MIF in the peritoneal fluids. In contrast, chemotactic activity could still be recovered, even though the MDR was suppressed. Mycobacteria functioned as a specific desensitizer not only with respect to cutaneous reactivity, as stated above, but also with respect to the production of chemotatic factor by peritoneal exudate cells. In contrast, mycobacteria functioned as a nonspecific desensitizer with respect to both the MDR and MIF production. These results suggest that the MDR may be an in vivo manifestation of MIF activity, whereas the cutaneous delayed hypersensitivity reaction may be more dependent upon chemotactic activity. These observations reported here, taken in conjunction with previously described in vitro studies, suggest that desensitization is a complex phenomenon which may be the result of several different mechanisms acting separately or in concert. The apparent discrepancies in the literature as to whether or not desensitization is a specific process would appear to arise from differences in the experimental model and the particular antigen used.


Acute enteritis associated with reovirus-like agents.
In Atlanta, from January to April 1975, reovirus-like agents (RLAs) were detected by a simplified electron-microscopic technique in the stools of 16 of 29 children with acute enteritis. Complement fixation tests with purified RLA antigens demonstrated antibody titer rises in seven children with RLA in their stools and in two mothers (one symptomatic) from whom acute and convalescent sera were available. Complement fixation tests performed on 207 individuals of varying ages and 60 laboratory workers indicated a high frequency of past infection with RLA, the highest frequency being in children 6 months to 4 years of age. These results corroborate the high rate of RLA detection in the stools of children with acute enteritis in other parts of the world and suggest that such infections can also occur in adults.


Endoscopic cystic duct stent as primary treatment for intrahepatic gallbladder perforation with abscess formation.
Intrahepatic gallbladder perforation with abscess formation is an uncommon presentation of biliary disease. There is no consensus on how to treat this condition, with strategies varying from percutaneous drainage to open cholecystectomy and washout. We present a case of a novel, minimally invasive treatment, using endoscopic retrograde cholangiopancreatography to place a transcystic drain as a bridge to laparoscopic cholecystectomy.


Impact of early postoperative creatinine increase on mid-term renal function after cystectomy.
To determine whether early acute kidney injury affects mid-term renal function, to identify risk factors for impaired mid-term renal function, and to highlight the evolution of plasma creatinine and estimated glomerular filtration rate in the first 12 months after cystectomy and urinary diversion. We conducted a single-center retrospective observational cohort study from 2000 to 2019. We included 900 consecutive patients undergoing cystectomy and urinary diversion. Patients with incomplete data and preoperative hemodialysis were excluded. Early acute kidney injury was defined as an increase in plasma creatinine of >50% or >26.5 μmol/L within 24 h after surgery. Multiple linear regression analysis was performed to model the association between risk factors and change in plasma creatinine and estimated glomerular filtration rate at 12 months. Early acute kidney injury was diagnosed in 183/900 patients (20.3%) and was associated with significant mid-term plasma creatinine increase compared to preoperative value (+10.0 μmol/L [95% confidence interval -1.5, 25.0] vs +4.0 μmol/L [-7.0, 13.0]; P < 0.001). Similarly, a significant estimated glomerular filtration rate change was found (-11.2 mL/min [95% confidence interval -19.8, 0.6] vs -4.9 mL/min [-15.6, 5.3]; P < 0.001). In the linear regression model, early acute kidney injury increased creatinine at 12 months by 9.8% (estimated glomerular filtration rate: decrease by 6.2 mL/min), male sex by 12.0%. Limitations include retrospective analysis from prospectively assessed data. Early acute kidney injury resulted in elevated plasma creatinine and decreased estimated glomerular filtration rate values 12 months postoperatively, albeit the clinical relevance remains questionable.


Pneumococcal antigen detection in bronchoalveolar lavage fluid from patients with pneumonia.
Pneumococcal pneumonia can be diagnosed by the detection of capsular antigen in sputum, serum, pleural fluid, or urine using countercurrent immunoelectrophoresis and latex agglutination. In addition, quantitative cultures of bronchoalveolar lavage (BAL) fluid are also reliable for establishing the aetiology of pneumonia. This study investigated the value of rapid detection of pneumococcal antigen in BAL fluid from patients with pneumonia. Pneumococcal antigen was detected by countercurrent immunoelectrophoresis and latex agglutination. Patients were grouped according to BAL quantitative culture results into pneumococcal pneumonia (n = 24), other known aetiology (n = 18), and unknown aetiology (n = 17). Thirteen patients with interstitial lung disease and without pneumonia served as a control group. In patients with pneumococcal pneumonia, antigen was detected by countercurrent immunoelectrophoresis in 50% and by latex agglutination in 54% of cases. In patients with pneumonia of unknown aetiology pneumococcal antigen was detected by latex agglutination in 53% of cases. Antigen was not detected in patients with pneumonia of other known aetiology or in control patients, yielding a specificity of 100%. In patients with pneumococcal pneumonia requiring fibreoptic bronchoscopy detection of pneumococcal antigen in BAL fluid may rapidly and accurately confirm the aetiology. Furthermore, in nearly half the cases of pneumonia of unknown aetiology antigen can be detected, suggesting that Streptococcus pneumoniae is a major causative agent in such patients.


Poor conditions of detention compromise ethical standards.
The ethical standards of police surgeons are being compromised by conflict between obligations to their paymasters, the police authorities, and their responsibilities to their patients, when these patients are prisoners detained in unacceptable conditions and where even minimum standards of medical care and management are difficult to deliver.


Trinity DNA detection platform by ultrasmooth and functionalized PEDOT biointerfaces.
An oligonucleotide-grafted poly(3,4-ethylenedioxythiophene) (PEDOT) thin film is developed for three DNA biosensor detection methods, including fluorescence, quartz crystal microbalance, and electrochemical methods. By electrocopolymerization of hydroxyl-functionalized EDOT and carboxylic-functionalized EDOT in microemulsion solutions, ultrasmooth films with a controlled surface density of carboxylic groups are created. The probe oligonucleotides are immobilized on PEDOT thin films by using a N-hydroxysuccinimide and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride coupling method. By monitoring the DNA hybridization efficiency on thin films with different oligonucleotide densities, the optimized density for DNA hybridization is obtained. The feasibility and limitation of using this platform for electrochemical detection are also discussed.


Effects of pentoxifylline administration on histomorphological parameters of streptozotocin-induced diabetic rat testes.
The effect of pentoxifylline (PTX) administration on histomorphological parameters of streptozotocin (STZ)-induced type 1 diabetes mellitus (DM) in male rat testes were evaluated. We randomly divided 40 male rats into the following four groups: group 1: control or normal glycemic (NG) rats; group 2 or NG rats that received only normal saline (NS), (NG+NS); group 3 or diabetic rats which were not treated by PTX (DM+vehicle solution (NS)); and group 4 which comprised diabetic rats treated with 50 mg/kg of PTX (DM+PTX). Type 1 DM was induced by intraperitoneal injection of STZ (55 mg/kg). Rats were held for 30 days after which the experimental group received PTX twice daily (25 mg/kg) or NS. After 14 days of treatment by PTX or NS, the left testes from all rats were extracted and prpared for histological study. Apoptotic cells, blood vessel density, and spermatogenesis were evaluated. Data were analyzed by ANOVA test. PTX-treated-diabetic rats showed a significant decrease in number of apoptotic cells and decrease in blood vessel density compared to the DM+NS rats. A significant increase in spermatogenesis was observed in the PTX-treated diabetic group, compared to the DM+NS groups. It was concluded that PTX administration to STZ-induced type 1 DM rats affected apoptotic cell number positively. Moreover, blood vessel density significantly decreased and improvements were observed in spermatogenesis.


Precisely Tracking Childhood Death.
Little is known about the specific causes of neonatal and under-five childhood death in high-mortality geographic regions due to a lack of primary data and dependence on inaccurate tools, such as verbal autopsy. To meet the ambitious new Sustainable Development Goal 3.2 to eliminate preventable child mortality in every country, better approaches are needed to precisely determine specific causes of death so that prevention and treatment interventions can be strengthened and focused. Minimally invasive tissue sampling (MITS) is a technique that uses needle-based postmortem sampling, followed by advanced histopathology and microbiology to definitely determine cause of death. The Bill & Melinda Gates Foundation is supporting a new surveillance system called the Child Health and Mortality Prevention Surveillance network, which will determine cause of death using MITS in combination with other information, and yield cause-specific population-based mortality rates, eventually in up to 12-15 sites in sub-Saharan Africa and south Asia. However, the Gates Foundation funding alone is not enough. We call on governments, other funders, and international stakeholders to expand the use of pathology-based cause of death determination to provide the information needed to end preventable childhood mortality.


Breast cancer metastases to the head and neck: Case series and literature review.
Breast cancer is the most common cancer in women and is the second most common cause of cancer-related death. Despite the relatively high prevalence of this disease, breast cancer manifestations in the head and neck are relatively rare. Supraclavicular lymphadenopathy and bony metastases to the mandible and maxilla are the most common manifestation of breast cancer in the head and neck. Head and neck metastases are the first presentation of distant disease in approximately one-third of cases. The prognosis of breast cancer with distant metastases to the head and neck is generally poor, and the management of these lesions is controversial. Overall extent of disease and individual patient prognosis must guide treatment decisions. Atypical cases including maxillary sinus mass, jugular foramen mass, and dermal metastases are presented. Metastatic breast cancer is a rare diagnosis in the head and neck, yet metastatic disease from an infraclavicular primary deserves inclusion on any comprehensive differential diagnosis list. In women, breast carcinoma is the most common infraclavicular primary to metastasize to the head and neck.


Temperature Calibration for In Situ Environmental Transmission Electron Microscopy Experiments.
In situ environmental transmission electron microscopy (ETEM) experiments require specimen heating holders to study material behavior in gaseous environments at elevated temperatures. In order to extract meaningful kinetic parameters, such as activation energies, it is essential to have a direct and accurate measurement of local sample temperature. This is particularly important if the sample temperature might fluctuate, for example when room temperature gases are introduced to the sample area. Using selected-area diffraction (SAD) in an ETEM, the lattice parameter of Ag nanoparticles was measured as a function of the temperature and pressure of hydrogen gas to provide a calibration of the local sample temperature. SAD permits measurement of temperature to an accuracy of ±30°C using Ag lattice expansion. Gas introduction can cause sample cooling of several hundred degrees celsius for gas pressures achievable in the ETEM.


Aberrant O-GlcNAcylated Proteins: New Perspectives in Breast and Colorectal Cancer.
Increasing glucose consumption is thought to provide an evolutionary advantage to cancer cells. Alteration of glucose metabolism in cancer influences various important metabolic pathways including the hexosamine biosynthesis pathway (HBP), a relatively minor branch of glycolysis. Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), an end product of HBP, is a sugar substrate used for classical glycosylation and O-GlcNAcylation, a post-translational protein modification implicated in a wide range of effects on cellular functions. Emerging evidence reveals that certain cellular proteins are abnormally O-GlcNAc modified in many kinds of cancers, indicating O-GlcNAcylation is associated with malignancy. Since O-GlcNAc rapidly on and off modifies in a similar time scale as in phosphorylation and these modifications may occur on proteins at either on the same or adjacent sites, it suggests that both modifications can work to regulate the cellular signaling pathways. This review describes the metabolic shifts related to the HBP, which are commonly found in most cancers. It also describes O-GlcNAc modified proteins identified in primary breast and colorectal cancer, as well as in the related cancer cell lines. Moreover, we also discuss the potential use of aberrant O-GlcNAcylated proteins as novel biomarkers of cancer.


Predictors of Increased Lactate in Neonatal Cardiac Surgery: The Impact of Cardiopulmonary Bypass.
Hyperlactatemia develops intraoperatively during cardiac surgery and is associated with postoperative mortality. This study aimed to determine the factors that lead to an increase in lactate during cardiopulmonary bypass (CPB) in neonates undergoing cardiac surgery. Retrospective study from July 2015 to December 2018. Academic tertiary children's hospital. The study comprised 376 neonates. No interventions were performed. Lactate measurements at prebypass, upon initiation of CPB and before coming off CPB, last in the operating room, and first in the cardiac intensive care unit were collected. The changes in lactate levels were compared using the nonparametric Wilcoxon signed rank test for paired data. Univariate and multivariate median regression models of the change during CPB were determined. The cohort characteristics were male (60%), median age 5 days (range 1-30), and weight 3.2 kg (range 1.5-4.7). Most patients had a STAT score of 4 (45%) or 5 (23%). Significant increases in lactate were observed from pre-CPB to start of CPB (p < 0.001) and from start to end of CPB (p < 0.001). In the multivariate regression analysis, duration of circulatory arrest (coefficient = 1.216; 95% confidence interval [CI] 0.754-1.678; p < 0.001), duration of mean arterial pressure < 25 mmHg (coefficient = 0.423; 95% CI 0.196-to- 0.651; p < 0.001), and duration of mean arterial pressure between 35 and 39 mmHg (coefficient = -0.246; 95% CI -0.397 to -0.095; p = 0.001) were identified as significant independent predictors of the lactate change per 30- minutes duration. These results emphasized the importance of blood pressure management during CPB and the importance of the duration of circulatory arrest.


Secretory carcinoma of the breast.
Secretory carcinoma of the breast is a rare but histologically distinct variant of invasive ductal carcinoma that has an indolent growth pattern and a more favorable prognosis than that of typical ductal carcinoma. We present the imaging and histopathologic findings of a case of this tumor that initially manifested as a palpable mass in the left breast of a 31-year-old woman. It appeared sonographically as a round, well-circumscribed but microlobulated hypoechoic solid mass. Secretory carcinoma of the breast may resemble other well-circumscribed breast carcinomas as well as some benign masses, including fibroadenomas. Breast imagers should be aware of this rare tumor's nonspecific imaging features and clinical implications when making a differential diagnosis of solid breast masses.


High resolution imaging and five-year tuberculosis contact outcomes.
The evolution of tuberculosis (TB) disease during the clinical latency period remains incompletely understood. 250 HIV-uninfected, adult household contacts of rifampicin-resistant TB with a negative symptom screen underwent baseline 18F-Fluorodeoxyglucose positron emission and computed tomography (PET/CT), repeated in 112 after 5-15 months. Following South African and WHO guidelines, participants did not receive preventive therapy. All participants had intensive baseline screening with spontaneous, followed by induced, sputum sampling and were then observed for an average of 4.7 years for culture-positive disease. Baseline PET/CT abnormalities were evaluated in relation to culture-positive disease. At baseline, 59 (23.6%) participants had lung PET/CT findings consistent with TB of which 29 (11.6%) were defined as Subclinical TB, and 30 (12%) Subclinical TB-inactive. A further 83 (33.2%) had other lung parenchymal abnormalities and 108 (43.2%) had normal lungs. Over 1107-person years of follow-up 14 cases of culture-positive TB were diagnosed. Six cases were detected by intensive baseline screening, all would have been missed by the South African symptom-based screening strategy and only one detected by a WHO-recommended chest X-Ray screening strategy. Those with baseline Subclinical TB lesions on PET/CT were significantly more likely to be diagnosed with culture-positive TB over the study period, compared to those with normal lung parenchyma (10/29 [34.5%] vs 2/108 [1.9%], Hazard Ratio 22.37 [4.89-102.47, p<0.001]). These findings challenge the latent/active TB paradigm demonstrating that subclinical disease exists up to 4 years prior to microbiological detection and/or symptom onset. There are important implications for screening and management of TB.