The effect of sodium bicarbonate oral rinse on salivary pH and oral microflora: A prospective cohort study.
Present study is designed to explore the effect of sodium bicarbonate oral rinse on salivary pH and oral micro flora. Twenty five healthy subjects were recruited for the study in department of dentistry in Era Medical College. Subjects were abstained from tooth brushing overnight pre rinse (control) samples were collected after one hour of dinner and were asked to rinse with pre calibrated freshly prepared sodium bicarbonate solution. The salivary samples were then collected the following morning using sterile gauze in marked bottles. Aerobic bacterial culture was done by plating the sample directly from the swab on the surface of Blood agar and Mac Conkeys media respectively. The colony forming units and ph were calculated for the pre rinse and post rinse saliva sample. Results shows that salivary pH increased significantly after sodium Bicarbonate oral rinse. There was a marginal decrease in number of CFU/ml for bacteria especially Viridans Streptococci, Moraxella species. Sodium Bicarbonate oral rinse may be considered as a cheap and effective alternative for chlorhexidine and alcohol based mouth wash, especially where long duration usage is required.


Post-infectious autoimmune disorders: Sydenham's chorea, PANDAS and beyond.
Infections, and the resulting immune response to these infections, have recently received increased recognition as pathogenic mechanisms for neuropsychiatric disorders. Sydenham's chorea (SC), a widely recognized post-streptococcal autoimmune disorder, represents a model for this proposed pathogenesis. In SC, a dysregulated immune response to a streptococcal infection is hypothesized to result in inflammation of neuronal networks, particularly the basal ganglia nuclei. The resulting dysfunction in the basal ganglia nuclei are hypothesized to lead to a constellation of adventitious movements and psychiatric symptoms, which investigations have shown are amenable to immunomodulatory therapies. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections) has been proposed as a variant of SC, and is hypothesized to share a pathogenic mechanism, despite a unique symptom profile of predominantly psychiatric symptoms. In this review, we present the clinical aspects of both disorders, the data for potential shared etiopathogenesis between them, and the evidence for the therapeutic use of immunomodulatory therapies for the symptoms of SC and PANDAS. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease.


Senescence-associated secretory phenotype and its impact on oral immune homeostasis.
The senescence-associated secretory phenotype (SASP), which accumulates over the course of normal aging and in age-related diseases, is a crucial driver of chronic inflammation and aging phenotypes. It is also responsible for the pathogenesis of multiple oral diseases. However, the pathogenic mechanism underlying SASP has not yet been fully elucidated. Here, relevant articles on SASP published over the last five years (2017-2022) were retrieved and used for bibliometric analysis, for the first time, to examine SASP composition. More than half of the relevant articles focus on various cytokines (27.5%), growth factors (20.9%), and proteases (20.9%). In addition, lipid metabolites (13.1%) and extracellular vesicles (6.5%) have received increasing attention over the past five years, and have been recognized as novel SASP categories. Based on this, we summarize the evidences demonstrating that SASP plays a pleiotropic role in oral immunity and propose a four-step hypothetical framework for the progression of SASP-related oral pathology-1) oral SASP development, 2) SASP-related oral pathological alterations, 3) pathological changes leading to oral immune homeostasis disruption, and 4) SASP-mediated immune dysregulation escalating oral disease. By targeting specific SASP factors, potential therapies can be developed to treat oral and age-related diseases.


Myostatin is expressed in bovine ovarian follicles and modulates granulosal and thecal steroidogenesis
Myostatin plays a negative role in skeletal muscle growth regulation but its potential role in the ovary has received little attention. Here, we first examined relative expression of myostatin (MSTN), myostatin receptors (ACVR1B, ACVR2B and TGFBR1) and binding protein, follistatin (FST), in granulosa (GC) and theca (TC) cells of developing bovine follicles. Secondly, using primary GC and TC cultures, we investigated whether myostatin affects steroidogenesis and cell number. Thirdly, effects of gonadotropins and other intrafollicular factors on MSTN expression in GC and TC were examined. MSTN, ACVR1B, TGFBR1, ACVR2B and FST mRNA was detected in both GC and TC at all follicle stages. Immunohistochemistry confirmed follicular expression of myostatin protein. Interestingly, MSTN mRNA expression was lowest in GC of large oestrogen-active follicles whilst GC FST expression was maximal at this stage. In GC, myostatin increased basal CYP19A1 expression and oestradiol secretion whilst decreasing basal and FSH-induced HSD3B1 expression and progesterone secretion and increasing cell number. Myostatin also reduced IGF-induced progesterone secretion. FSH and dihydrotestosterone had no effect on granulosal MSTN expression whilst insulin-like growth factor and tumour necrosis factor-alpha suppressed MSTN level. In TC, myostatin suppressed basal and LH-stimulated androgen secretion in a follistatin-reversible manner and increased cell number, without affecting progesterone secretion. LH reduced thecal MSTN expression whilst BMP6 had no effect. Collectively, results indicate that, in addition to being potentially responsive to muscle-derived myostatin from the circulation, myostatin may have an intraovarian autocrine/paracrine role to modulate thecal and granulosal steroidogenesis and cell proliferation/survival.


Experimental transmission of two young and one suspended bovine spongiform encephalopathy (BSE) cases to bovinized transgenic mice.
Bovine spongiform encephalopathy (BSE) is caused by a prion that primarily consists of an abnormal isoform of the prion protein (PrP(Sc)). Since PrP(Sc) is partially resistant to proteolytic digestion, the routine diagnosis of BSE is based on the immunological detection of the proteinase K (PK)-resistant moiety of PrP(Sc) (PrP(core)). However, transmission studies are indispensable in order to demonstrate prion infectivity and to analyze prion characteristics. Transmission experiments were accordingly performed on 2 young BSE cases (BSE/JP8, BSE/JP9) and 1 suspected BSE case (Suspended-1) that were detected by the BSE screening program in Japan. In this study, we attempted to transmit the prion from these 3 animals by using transgenic mice overexpressing bovine PrP (TgBoPrP). In spite of the use of BSE-sensitive transgenic mice, none of the mice developed neurological signs nor accumulated PrP(Sc) in their brains for more than 600 days post-inoculation, even with subsequent blind passages. The results of a dilution experiment using the classical BSE prion indicated that prion infectivity in these 3 cattle was below the detection limit of 10(3.0) LD(50)/g.


Ciprofloxacin-associated hemolytic-uremic syndrome.
To report the first case of ciprofloxacin-associated hemolytic-uremic syndrome (HUS). A 53-year-old white man was treated with chemotherapy for acute lymphoblastic leukemia. Four weeks after initiation of treatment, he recovered his blood cell counts, but developed fever and was prescribed oral ciprofloxacin 500 mg twice daily. After 4 doses, he developed the typical features of HUS manifested by microangiopathic hemolytic anemia, oliguric renal failure, and thrombocytopenia. The medication was withdrawn, and he received 5 sessions of plasma exchange. He recovered completely and has normal renal function. Secondary HUS or its related syndrome, thrombotic thrombocytopenic purpura (TTP), is uncommon, but has been reported in association with cancer, chemotherapy, and a variety of medications. Our case represents a possible adverse drug reaction to ciprofloxacin according to the Naranjo probability scale. It is the first reported case of HUS associated with ciprofloxacin. Ciprofloxacin use was followed by HUS in our patient and was possibly causally related. Early detection, discontinuation of the offending medication, and treatment of HUS/TTP is critical.


Helminths in Leuciscus cephalus from the river Adda, Lombardy, Northern Italy.
Chubs (Leuciscus cephalus) were caught at various locations along the river Adda and from Lake of Como (Lombardy, Northern Italy) and endoparasitic helminths were studied in order to integrate the knowledge on distribution of helminth fauna of chubs in Lombardy and to investigate on the structure of its parasite infracommunities with respect to different habitat typologies. The following species of parasites were isolated: Pomphorynchus laevis, Allocreadium markewitschi, Parasymphylodora markewitschi, Raphidascaris acus, Hysterothylacium aduncum and Molnaria intestinalis. P laevis resulted the most common species (P = 56.52%). The mean abundances and the prevalence of helminths were different in chubs according to the sampling site. The mean abundances were lower in chubs sampled in the lake than those sampled in the river. Particularly, P. laevis showed the highest prevalences in fish captured in the river sites. The trematodes (P. markewitschi and A. markewitschi) seem to be more related with "lake" typology. These results are discussed and related to differences in life cycle of these parasites and to other factors like sampling period and the conditions of the aquatic sites that could influence the richness of parasite species.


Metal-dependent repression of siderophore and biofilm formation in Actinomyces naeslundii.
Actinomyces naeslundii is a pioneer of the oral cavity and forms a biofilm on the tooth's surface. Most bacteria require iron for survival and in pathogenic bacteria iron availability regulates virulence gene expression. Metal-dependent repressors control gene expression involved in metal transport and uptake including siderophores. Siderophores are small molecules synthesized by bacteria and fungi to acquire iron. The A. naeslundii genome was searched for a gene encoding a metal-dependent repressor. Actinomyces metal-dependent repressor or amdR was identified. The AmdR protein was examined for its ability to bind to the promoter sequence of a gene encoding the siderophore uptake (sid gene). According to gel shift assays, AmdR binds to the sid gene promoter sequences. In the authors' model, when iron is available AmdR binds to the sid promoter and represses sid gene expression. To further explore the role of AmdR, an amdR-defective strain of A. naeslundii was constructed and biofilm formation and siderophore production were evaluated. When iron is removed from the medium A. naeslundii increases biofilm and siderophore production. However, amdR-defective A. naeslundii is less sensitive to metal ion concentrations in the growth medium.


[In vitro study on shear bond strength of veneering ceramics to zirconia].
To investigate the shear bond strength between veneering ceramic and zirconia core in different all-ceramic systems. Twenty disk-shaped specimens with 8 mm in diameter and 3 mm in height for each zirconia system (Lava, Cercon, IPS e.max ZirCAD, Procera) were fabricated respectively and divided into four groups: Lava group, Cercon group, IPS e.max ZirCAD group, Procera group. For each group, 10 specimens were sintered with 1 mm corresponding veneering ceramic, while the other were sintered with 2 mm corresponding veneering ceramic respectively. The shear bond strength and fracture mode of specimens were observed and determined. The values of shear bond strength for Lava, Cercon, IPS e.max ZirCAD and Procera were (13.82 +/- 3.71), (13.24 +/- 2.09), (6.37 +/- 4.15), (5.19 +/- 5.31) MPa in the group of 1 mm thicked veneering ceramics, respectively, while the values in the group of 2mm thicked veneering ceramics were (38.77 +/- 1.69), (21.67 +/- 3.34), (12.70 +/- 4.24), (9.94 +/- 6.67) MPa. The values of Lava and Cercon groups were significantly higher than that of IPS e.max ZirCAD and Procera groups (P < 0.05). And the values of 2 mm thicked veneering ceramic group were significantly higher than that in 1 mm thicked groups (P < 0.05). Adhesive fracture between core and veneering ceramics were observed in the fracture modes of most specimens. The shear bond strength of veneering ceramic to the zirconia framework are different from the zirconia system we chose, and the thickness of veneering ceramic has a great impact on its shear bond strength.


A hybrid double perovskite ferroelastic exhibiting the highest number of orientation states.
Integrating NH4+ as a B'-site ion within a three-dimensional double hybrid perovskite resulted in a novel high-temperature ferroelastic, (Me3NOH)2(NH4)[Co(CN)6], which uniquely demonstrates a reversible triclinic-to-cubic phase transition at 369 K and offers a record-setting 24 orientation states, the highest ever reported among all ferroelastics.


A novel working memory task for preschoolers: sensitivity to age differences from 3-5 years.
Working memory (WM) plays an important role in children's learning and is linked to later academic and occupational success. Understanding the early development of WM can provide critical clues regarding the underlying structure of executive functions and how they change over the life span. The main objectives of the present study were to (1) investigate age differences in the development of three components of WM (retrieval, substitution, transformation) on a novel preschool WM measure and (2) explore whether findings are consistent with the hierarchical model of WM development by examining perseverative and non-perseverative WM errors. Perseverative errors were hypothesized to be more strongly associated with problems substituting and transforming a representation held in mind, whereas non-perseverative errors were hypothesized to be associated with problems maintaining a representation in mind. Participants were 64 children ranging in age from 3.0 to 5.6 years. The results provide evidence for the sensitivity of the WM task to age differences from 3 to 5 years and support for the hierarchical model of WM development.


Effects of Overlap Between Consecutive Words on Speeded Typing Inform About Representation of Serial Order Within Words.
Typing is an everyday activity that requires people to use the correct serial order of phonological and orthographic forms of words. The evidence until now shows that different forms of representation of serial order have mixed contributions to typing performance. It is not clear whether and how representational overlap between subsequent words impacts the speed of typing. In three experiments, we used speeded typing of six-letter words. Including conditions with secondary task load to counteract potential ceiling effects, we varied whether subsequent words had partial overlap with respect to a chaining representation (e.g., kirsch → schaum; same triplet in different position) or, in addition, overlapped with respect to a potential positional representation (e.g., berlin → dublin, same triplet in the same position). Differently from previous findings (e.g., Snyder & Logan, 2014), Experiments 1 and 2 suggest that (a) chaining as well as positional coding are involved as representations of serial order and (b) partial overlap of representation of serial order leads to costs in typing speed. Experiment 3 demonstrated that full overlap speeds up typing. Across all experiments, the overlap effects were most revealed in the latency of the first keystroke, indicating the planning of motor programs. Taken together, the results suggest that even in highly practiced tasks such as typing, the activation of representations of serial order has side effects beyond the production of the current sequence.


A closer look at school bonding among African American adolescents in low-income communities: A latent class analysis.
Positive school bonding is a significant precursor to students' school success. However, African American youth report lower school success compared with their White counterparts. This study examined correlates of school bonding among 633 African American youth who were recruited from community settings in Chicago. Major findings indicated that negative peer norms, exposure to community violence, and poor mental health were negatively correlated with school bonding, while parental monitoring, positive self-regard, and future orientation were correlated with higher school motivation. Students classified as having high or moderate school bonding were more likely to live with both parents, experience higher levels of parental monitoring, and exhibit positive self-regard. Implications are discussed in view of these findings.


Systemic host inflammation induces stage-specific transcriptomic modification and slower maturation in malaria parasites.
Maturation rates of malaria parasites within red blood cells (RBCs) can be influenced by host nutrient status and circadian rhythm; whether host inflammatory responses can also influence maturation remains less clear. Here, we observed that systemic host inflammation induced in mice by an innate immune stimulus, lipopolysaccharide (LPS), or by ongoing acute Plasmodium infection, slowed the progression of a single cohort of parasites from one generation of RBC to the next. Importantly, plasma from LPS-conditioned or acutely infected mice directly inhibited parasite maturation during in vitro culture, which was not rescued by supplementation, suggesting the emergence of inhibitory factors in plasma. Metabolomic assessments confirmed substantial alterations to the plasma of LPS-conditioned and acutely infected mice, and identified a small number of candidate inhibitory metabolites. Finally, we confirmed rapid parasite responses to systemic host inflammation in vivo using parasite scRNA-seq, noting broad impairment in transcriptional activity and translational capacity specifically in trophozoites but not rings or schizonts. Thus, we provide evidence that systemic host inflammation rapidly triggered transcriptional alterations in circulating blood-stage Plasmodium trophozoites and predict candidate inhibitory metabolites in the plasma that may impair parasite maturation in vivo. IMPORTANCE Malaria parasites cyclically invade, multiply, and burst out of red blood cells. We found that a strong inflammatory response can cause changes to the composition of host plasma, which directly slows down parasite maturation. Thus, our work highlights a new mechanism that limits malaria parasite growth in the bloodstream.


Variation of HIV-1 mutation spectra among cell types.
The high rates of mutation, recombination, and replication drive HIV-1 diversity. In this study, we investigated how cell type affects viral mutation rate and mutation spectra. In studying four different cell types, no differences in mutation rate were observed, but intriguingly cell type differences impacted HIV-1 mutation spectra. This is the first description of significant differences in HIV-1 mutation spectra observed in different cell types in the absence of changes in the viral mutation rate.


Dynamic contrast-enhanced MRI versus 18F-FDG PET/CT: Which is better in differentiation between malignant and benign solitary pulmonary nodules?
To prospectively compare the discriminative capacity of dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) with that of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the differentiation of malignant and benign solitary pulmonary nodules (SPNs). Forty-nine patients with SPNs were included in this prospective study. Thirty-two of the patients had malignant SPNs, while the other 17 had benign SPNs. All these patients underwent DCE-MRI and 18F-FDG PET/CT examinations. The quantitative MRI pharmacokinetic parameters, including the trans-endothelial transfer constant (Ktrans), redistribution rate constant (Kep), and fractional volume (Ve), were calculated using the Extended-Tofts Linear two-compartment model. The 18F-FDG PET/CT parameter, maximum standardized uptake value (SUVmax), was also measured. Spearman's correlations were calculated between the MRI pharmacokinetic parameters and the SUVmax of each SPN. These parameters were statistically compared between the malignant and benign nodules. Receiver operating characteristic (ROC) analyses were used to compare the diagnostic capability between the DCE-MRI and 18F-FDG PET/CT indexes. Positive correlations were found between Ktrans and SUVmax, and between Kep and SUVmax (P<0.05). There were significant differences between the malignant and benign nodules in terms of the Ktrans, Kep and SUVmax values (P<0.05). The areas under the ROC curve (AUC) of Ktrans, Kep and SUVmax between the malignant and benign nodules were 0.909, 0.838 and 0.759, respectively. The sensitivity and specificity in differentiating malignant from benign SPNs were 90.6% and 82.4% for Ktrans; 87.5% and 76.5% for Kep; and 75.0% and 70.6% for SUVmax, respectively. The sensitivity and specificity of Ktrans and Kep were higher than those of SUVmax, but there was no significant difference between them (P>0.05). DCE-MRI can be used to differentiate between benign and malignant SPNs and has the advantage of being radiation free.


Permanent pacing post-Fontan is not associated with reduced long-term survival.
The Fontan procedure is the final stage of surgical palliation for a single-ventricle circulation. Significant complications are common including rhythm disturbance necessitating implantation of a permanent pacemaker. This has been widely considered a negative prognostic indicator. This single-centre, retrospective case control study involved all patients who underwent the Fontan procedure at the Leeds Congenital Heart Unit between 1990 and 2015 and have had regular follow-up in Yorkshire and Humber, United Kingdom. 167 Fontan patients were identified of which 2 were excluded for having a pre-procedure pacemaker. Of the remainder, 23 patients required a pacemaker. Outcomes were survival, early and late complications, need for further intervention and oxygen saturation in long-term follow-up. There was no difference in survival (30-day survival pacemaker 92.6%, sinus rhythm 90.5%, p = 0.66, 1-year pacemaker 11.1%, sinus rhythm 10.1%, p = 1). The pacemaker group was more likely to have cerebral or renal complications in the first-year post-procedure (acute kidney injury: sinus rhythm 0.8%, pacemaker 19.1%, p = 0.002). No difference was observed in longer term complications including protein losing enteropathy (sinus rhythm 3.5%, pacemaker 0% p = 1). There was no difference in saturations between the two groups at follow-up. Paced patients were more likely to have required further intervention, with a higher incidence of cardiopulmonary bypass procedures (sinus rhythm 6.3%, pacemaker 35%, p < 0.001). Despite an increase in early complications and the need for further interventions, pacemaker requirement does not appear to affect long-term survival following the Fontan procedure.


Bioinformatic Exploration for Prognostic Significance of Sphingolipid Metabolism-Related Genes in Invasive Ductal Carcinoma Using the Cancer Genome Atlas Cohort.
Sphingolipid metabolism is a highly controlled process that is involved in regulating bioactive lipid signaling pathways and serves important roles in several cellular processes in breast cancer. Invasive ductal carcinoma (IDC), which is characterized by the malignant proliferation of the ductal epithelium and stromal invasion, is the most common type of breast cancer. Recent advances in genetic research have accelerated the discovery of novel prognostic factors and therapeutic targets for the disease. The aim of the present study was to investigate the expression and prognostic significance of sphingolipid metabolism-related genes in female IDC. The present study used gene expression RNAseq data obtained from The Cancer Genome Atlas breast invasive carcinoma (TCGA BRCA) datasets. Sphingolipid metabolism-related genes exhibited dysregulated mRNA expression levels in IDC. The Student's t-test revealed that SMPDL3B, B4GALNT1, LPAR2, and LASS2 were significantly upregulated, while LASS3, LPAR1, B4GALT6, GAL3ST1, HPGD, ST8SIA1, UGT8, and S1PR1 were significantly downregulated in female IDC tissues compared with normal solid tissues. Kaplan-Meier survival analyses revealed that high SMPDL3B mRNA expression levels were associated with good prognosis in female IDC, suggesting that SMPDL3B plays a tumor suppressor role. To the best of our knowledge, the present study was the first to report that dysregulated expressions of SMPDL3B are significantly associated with age, estrogen receptor status, progesterone receptor status, and histological subtype. Taken together, our study indicated that SMPDL3B may have a pathophysiological role and serve as a novel prognostic biomarker in IDC.


Synthesis of (1R,4S,6R)-5,5,6-trimethyl-2-phosphabicyclo[2.2.2]octane and derivatives.
The novel primary phosphine (1R,3S)-[1,2,2-trimethyl-3-(phosphinomethyl)cyclopentyl]methyl methanesulfonate 3a (or tosylate 3b) has been prepared in three steps from (1R,3S)-camphoric acid with a view to utilising it as a synthon for the preparation of polycyclic phosphines. Efforts to prepare a [3.2.1] bicyclic product by internal cyclisation of 3a or 3b under various conditions were unsuccessful, but heating the neat compound at 140 degrees C for several hours gave the new asymmetric, bicyclic secondary phosphine, (1R,4S,6R)-5,5,6-trimethyl-2-phosphabicyclo[2.2.2]octane (PBO) as its methanesulfonic acid 5a (or p-toluenesulfonic acid 5b) salt. The cyclisation involves a skeletal rearrangement and occurs with high stereoselectivity to generate two new stereogenic carbon centres and a chiral phosphorus atom. The secondary phosphine was obtained after base treatment of 5a/b and several derivatives of the phosphine have been synthesised and characterised. Reaction of two mol equivalents of the borane adduct of PBO with alpha,alpha'-dichloro-ortho-xylene gave the bidentate derivative, o-C(6)H(4)(CH(2)PBO)(2).2BH(3), 12, and ultimately o-C(6)H(4)(CH(2)PBO)(2), 13. Complexes of 13 with Pd(II), Pt(II), Pt(0) and Mo(0) have been prepared and characterised by spectroscopic and analytical methods including single-crystal X-ray structure determinations of cis-Pd{o-C(6)H(4)(CH(2)PBO)(2)}Cl(2), 14, cis-Pt{o-C(6)H(4)(CH(2)PBO)(2)}Cl(2), 15 and Mo(CO)(4){o-C(6)H(4)(CH(2)PBO)(2)} 17.


Nodule-specific PLAT domain proteins are expanded in the Medicago lineage and required for nodulation.
Symbiotic nitrogen fixation in legumes is mediated by an interplay of signaling processes between plant hosts and rhizobial symbionts. In legumes, several secreted protein families have undergone expansions and play key roles in nodulation. Thus, identifying lineage-specific expansions (LSEs) of nodulation-associated genes can be a strategy to discover candidate gene families. Using bioinformatic tools, we identified 13 LSEs of nodulation-related secreted protein families, each unique to either Glycine, Arachis or Medicago lineages. In the Medicago lineage, nodule-specific Polycystin-1, Lipoxygenase, Alpha Toxin (PLAT) domain proteins (NPDs) expanded to five members. We examined NPD function using CRISPR/Cas9 multiplex genome editing to create Medicago truncatula NPD knockout lines, targeting one to five NPD genes. Mutant lines with differing combinations of NPD gene inactivations had progressively smaller nodules, earlier onset of nodule senescence, or ineffective nodules compared to the wild-type control. Double- and triple-knockout lines showed dissimilar nodulation phenotypes but coincided in upregulation of a DHHC-type zinc finger and an aspartyl protease gene, possible candidates for the observed disturbance of proper nodule function. By postulating that gene family expansions can be used to detect candidate genes, we identified a family of nodule-specific PLAT domain proteins and confirmed that they play a role in successful nodule formation.


Pediatric heart transplantation: results of 2- and 5-year follow-up.
Pediatric heart transplantation has become an accepted method of treatment for certain pediatric heart disease. From July 1986 to January 1993, we performed 25 orthotopic pediatric heart transplantations at the University of Minnesota Hospital and Clinics in 16 male patients and nine female patients. The average age was 8.5 years with a range from 7 days to 18 years. Three of the patients were younger than 1 year of age. The indications for transplantation included congenital heart disease in six patients and cardiomyopathy in 19 patients. Four of the patients with congenital heart disease had previously undergone a cardiac surgical procedure. Two patients with cardiomyopathy had mechanical assist devices in place at the time of transplantation. Donor age ranged from 2 months to 36 years. The donor organ ischemic time ranged from 60 minutes to 329 minutes, with an average of 191 minutes. Follow-up ranged from 6 to 84 months. Overall, there were seven deaths (28%) in the patients undergoing transplantation. Of the seven deaths, four (16%) were early (within 30 days) and three (14.3%) were late. The four early deaths were a result of donor organ failure, and the three late deaths a result of acute rejection. The 2-year survival for patients with a minimum 24-month evaluation was 79% (15 of 19). Of 12 patients available for 5-year assessment, 75% (9 of 12) were alive and doing well at the time this article was written. Pediatric heart transplantation can provide good intermediate and long-term survival for selected pediatric patients.


Antiviral treatment of a boy with EBV-associated hydroa vacciniforme.
Hydroa vacciniforme is one of the rarest forms of photosensitivity disorders of the skin. Effective treatment options are scarce and mainly constitute of strict sun protection. Lately, hydroa vacciniforme has been associated with Epstein-Barr virus infection. We present a patient with hydroa vacciniforme and concomitant previous/chronic Epstein-Barr virus infection. In this case, antiviral treatment was successful.


Papillon-lefevre syndrome with congenital hepatic fibrosis.
Papillon Lefevre syndrome (PLS) is a rare autosomal recessive disorder, which is characterized by palmar-plantar hyperkeratosis, periodontitis, and premature loss of dentition. We report a 16 years old girl with PLS. The patient presented at 08 years of age with complaints of corn on the feet and hands, and failure to thrive. On examination, her upper primarily canines were loose, she had severe periodontitis, eruption of permanent teeth, diffuse eritematous and hyperkeratotic palms and soles that suggested the syndrome. During the follow-up, the patient was diagnosed to have congenital hepatic fibrosis (CHF) when she was 16 years old, while she was being investigated for the etiology of her splenomegaly and pancytopenia. We report a patient with PLS associated with CHF, an association that has not been previously described. Abbreviations-HbsAg: Hepatitis B virus surface antigen, Anti Hbs: Antibody against Hepatitis B surface antigen, Anti Hbc IgM: Antibody against Hepatitis B cor antigen immunglobulin M, Anti dsDNA: Antibody against double stranded deoksiribonucleic acid, Anti HCV: Antibody against Hepatit C virus, Anti HIV: Antibody against human immun deficiency virus, AST: Aspartat amino transferase, ALT: Alanin amino transferase, Gamma-GT: Gamma glutamyl transferase, LDH: Lactate dehydrogenase & MRI: Magnetic resonance imaging.


Rational Adaptation of L3MBTL1 Inhibitors to Create Small-Molecule Cbx7 Antagonists.
Chromobox homolog 7 (Cbx7) is an epigenetic modulator that is an important driver of multiple cancers. It is a methyl reader protein that operates by recognizing and binding to methylated lysine residues on specific partners. Herein we report our efforts to create low-molecular-weight inhibitors of Cbx7 by making rational structural adaptations to inhibitors of a different methyl reader protein, L3MBTL1, inhibitors that had previously been reported to be inactive against Cbx7. We evaluated each new inhibitor for Cbx7 inhibition by fluorescence polarization assay, and also confirmed the binding of selected inhibitors to Cbx7 by saturation-transfer difference NMR spectroscopy. This work identified multiple small-molecule inhibitors with modest (IC50 : 257-500 μm) potency.


Are rare variants really independent?
Recent advances in genotyping with high-density markers allow researchers access to genomic variants including rare ones. Linkage disequilibrium (LD) is widely used to provide insight into evolutionary history. It is also the basis for association mapping in humans and other species. Better understanding of the genomic LD structure may lead to better-informed statistical tests that can improve the power of association studies. Although rare variant associations with common diseases (RVCD) have been extensively studied recently, there is very limited understanding, and even controversial view of LD structures among rare variants and between rare and common variants. In fact, many popular RVCD tests make the assumptions that rare variants are independent. In this report, we show that two commonly used LD measures are not capable of detecting LD when rare variants are involved. We present this argument from two perspectives, both the LD measures themselves and the computational issues associated with them. To address these issues, we propose an alternative LD measure, the polychoric correlation, that was originally designed for detecting associations among categorical variables. Using simulated as well as the 1000 Genomes data, we explore the performances of LD measures in detail and discuss their implications in association studies.


Tunneled hemodialysis central venous catheters prevalence and bloodstream infection rates in Northern Italy: A survey of the "East Lombardy Nephrological Network".
Tunneled central venous catheter (tCVCs) is a vascular access frequently employed in hemodialysis patients. Catheter-related bloodstream infections (CRBSI) are potentially life-threatening complications. We performed a retrospective survey regarding tCVCs prevalence as well as the CRBSI incidence and management within five hospitals in the Brescia province belonging to the "East Lombardy Nephrological Network"; this study was based upon 18 queries regarding the years 2020 and 2021. The data collected refer to an overall hemodialysis population of 736 patients in 2020 and 745 patients in 2021. The prevalence of tCVCs was respectively 22.1% and 24.2% with the initial placement being performed with fluoroscopy support in 80% of the centers. CRBSI incidence was respectively 0.88 and 0.77 episodes per 1000 days of tCVC use. When the CRBI was caused by Staphylococcus Aureus (SA) or Pseudomonas, differently from the recommendation of the KDOQI guidelines, the removal or the substitution of the tCVC did not occur immediately at the time of the diagnosis of the infection but only when the specific antibiotic therapy failed. A nose swab aimed at identifying SA carriers was performed in 60% of centers. The policy regarding the referral to other specialists (infectious disease specialist and microbiologist) was heterogenous across the centers according to their specific logistics. This retrospective survey performed by the "East Lombardy Nephrological Network" within the Brescia province describes the prevalence of tCVCs use as well as the incidence and management of CRBSIs in the hemodialysis patients of this area. The clinical impact of the differences in terms of clinical approach detected compared to the KDOQI guidelines will need to be clarified ideally in prospective studies.


Financial journalism in today's high-frequency news and information era.
This study relies on 22 expert interviews and a survey among 40 financial journalists in the United States to reassess the role of financial journalists for financial markets in today's high-frequency information and news era. Findings point to a discrepancy between the ideal active watchdog role journalists picture for themselves and their actual role enactment. Furthermore, the process of constructing and distributing financial news has been found to be self-referential within the financial system, leaving little room for alternative voices. In this sense, the influence of regular financial reporting in driving stock market prices has been found to be limited but contingent on various factors such as unexpected news, repeatedly negative reporting, or news about a merger. Eventually, facing the proliferation of online news, journalists have raised a general concern regarding the loss of journalistic values, but they also see potentials for their discipline in light of automated reporting and online news.


Robust measurement of group delay in the presence of density fluctuations by means of ultrafast swept reflectometry.
It is well known that reflectometric measurements can be seriously disturbed by density fluctuations. In this paper the basic mechanisms that critically affect the measurements are outlined with the help of a simplified two-dimensional model which simultaneously mimics the dynamic of the plasma turbulence and the frequency sweep. It turns out that an adequate modulation rate can easily overcome the adverse effect of wave scattering produced by short wavelength fluctuations even when measurements taken at a single frequency would fail. Nevertheless the Doppler effect caused by long wavelength fluctuations can produce a substantial shift in the group delay, which accounts for nonmonotonous density profile reconstructions. In turn this effect can be corrected using a very fast ascending and descending frequency modulation, similarly to what is done in FM radars. The technical feasibility of such a system is demonstrated using the Ka band reflectometer of RFX, where a triangular modulation of 2.5 MHz, with a bidirectional modulation rate up to 4 GHz/200 ns, has been obtained.


Simple affinity procedure for the purification of mammalian viral reverse transcriptases.
Polyguanylic acid was found to be a potent inhibitor of RNase H associated with mammalian viral reverse transcriptase, indicating a strong interaction between polyguanylic acid and the reverse transcriptase protein. Based on this observation, we have developed three simple procedures for the purification of mammalian viral reverse transcriptases. In the first procedure, a nucleic acid-free extract of Rauscher murine leukemia virus was applied to a column of phosphocellulose and the reverse transcriptase was eluted by a low concentration (50 microM) of polyguanylic acid. Polyadenylic acid and polyuridylic acid could not replace polyguanylic acid for the elution. In the second procedure, a polyuridylic acid-Sepharose column was substituted for phosphocellulose, and the elution was again achieved by polyguanylic acid. In the third affinity procedure, the reverse transcriptase in a nucleic acid-free viral extract was incubated in the cold with 50 microM polyguanylic acid and the complex was adsorbed onto a DEAE-cellulose column. After washing to remove uncomplexed and weakly complexed proteins, the reverse transcriptase was eluted in a concentrated form at 0.3 M NaCl with a recovery of greater than 70%. by polyacrylamide gel analysis in the presence of sodium dodecyl sulfate, the enzyme appeared to be nearly pure.


Identification of Anti-Inflammatory Compounds from Peucedanum praeruptorum Roots by Using Nitric Oxide-Producing Rat Hepatocytes Stimulated by Interleukin 1β.
The roots of Peucedanum praeruptorum Dunn and Angelica decursiva Franchet et Savatier are designated Zenko, which is a crude drug defined by the Japanese Pharmacopoeia. This crude drug is used as an antitussive and an expectorant and is included in the Kampo formula Jinsoin, which improves cough, fever, and headache. Although the anti-inflammatory effects of this crude drug have been determined, the constituents responsible for this effect remain unknown. To investigate biologically active compounds, rat hepatocytes were used, which produce proinflammatory mediator nitric oxide (NO) in response to proinflammatory cytokine interleukin 1β (IL-1β). A methanol extract of P. praeruptorum roots, which suppressed IL-1β-induced NO production, was fractionated into three crude fractions (ethyl acetate (EtOAc)-soluble, n-butanol-soluble, and water-soluble fractions) based on hydrophobicity. The EtOAc-soluble fraction markedly inhibited NO production. After this fraction was purified, three biologically active compounds were identified as praeruptorins A, B, and E, the contents of which were high. A comparison of their activities indicated that praeruptorin B exhibited the highest potency to inhibit NO production by decreasing inducible NO synthase expression and suppressed the expression of mRNAs encoding proinflammatory cytokines. Collectively, the three praeruptorins may primarily contribute to the anti-inflammatory effects of P. praeruptorum roots.


A Mediterranean-style diet and metabolic syndrome.
A moderate increase in physical activity and a detailed and tailored Mediterranean-style diet reduce the prevalence of metabolic syndrome and associated cardiovascular risks through reducing systemic vascular inflammation and endothelium dysfunction, particularly in those patients who do not lose weight.


THE ACCURACY OF PHYLOGENETIC ESTIMATION USING THE NEIGHBOR-JOINING METHOD.
We studied the factors affecting the accuracy of the neighbor-joining (NJ) method for estimating phylogenies by simulating character change under different evolutionary models applied to twenty different 8-OTU tree topologies that varied widely with respect to tree imbalance and stemminess. The models incorporated three evolutionary rates-constant, varying among lineages, varying among characters-and three evolutionary contexts concerning patterns of character change relative to speciation events-phyletic, speciational, and punctuational. All combinations of the rate and context models were studied. In addition, three different absolute rates of change were investigated. To measure the accuracy, the strict consensus index was computed between the estimated tree and the tree topology along which the data had been generated. The results were analyzed by analysis of variance and compared to a previous study that evaluated UPGMA clustering and maximum parsimony (MP) as phylogenetic estimation techniques. We found evolutionary context and tree imbalance to be the most important factors affecting the accuracy of the NJ method. NJ was more accurate than UPGMA or MP in terms of the average strict consensus index over all treatments. However, no one method was more accurate than the other two for all combinations of treatments. Higher absolute rate of change generally resulted in higher accuracy for all three methods.


Use of the rocking bed in the treatment of neurogenic respiratory insufficiency.
We describe 53 patients who received ventilatory support with a rocking bed. Diagnoses included previous poliomyelitis (30), muscular dystrophy (12), motor neurone disease (4), adult-onset acid maltase deficiency (4) and a miscellaneous group (3). Patients presented with respiratory insufficiency characterized by diaphragm weakness, progressive nocturnal hypoventilation and/or acute or chronic respiratory failure. Domiciliary rocking beds were used by 43 patients for a mean of 16.0 years (range 1 month to 35 years). Most patients were able to breathe adequately by day when sitting or standing, but needed assistance by rocking bed for 6-11 h when lying down for sleep. The rocking bed was well-tolerated, and associated with both symptomatic relief and amelioration of arterial blood gas abnormalities. Seventeen of these 43 patients discontinued its use, either because of discomfort (9) or increasing respiratory insufficiency (8). The rocking bed is a valuable adjunct in the management of the respiratory insufficiency associated with neuromuscular disease.


Critical care in the surgical global period.
This article explores the rules and regulations from Current Procedural Terminology (CPT) code set and US Medicare and Medicaid Services (Medicare) regarding multiple physicians reporting critical care services during the global period. The article takes into account the critical care definitions, regulations, documentation requirements, and services each provider can report to Medicare. A clinical scenario based on literature supporting the types of complications and care that might typically be included in the post-operative period for a patient who is surgically treated for a type A aortic dissection was analyzed. It was determined that multiple physicians may provide critical care services to a single patient during the global period. The physician who performed the primary procedure cannot report critical care separately unless documentation supporting use of modifier 25 (significant, separately identifiable services) or 24 (unrelated services) supports that critical care is unrelated to the global period. Other physicians may report critical care services separately if specific criteria are met. To report critical care services to Medicare, the patient's condition must meet the Medicare definition of critical care and the physicians should generally represent different specialties providing different aspects of care to the critically ill or injured patient as defined by Medicare. There should be no overlap in time of services provided by each physician. Each physician's documentation should clearly support medical necessity with the diagnosis demonstrating the critical nature of the patients' illness, the total time spent providing critical care, the critical care service provided, and other contributing factors.


Artifacts and pitfalls in MR imaging of the orbit: a clinical review.
High-resolution magnetic resonance (MR) imaging of the orbit has become widely accepted as a valuable diagnostic technique. However, there are a number of artifacts and pitfalls associated with orbital MR imaging. Chemical shift artifacts may be induced by orbital fat or silicone oil used to treat retinal detachment. Motion artifacts are caused primarily by unavoidable globe motion during imaging. Artifacts due to a nonuniform magnetic field are particularly noticeable at air-tissue interfaces but may also be caused by incomplete fat saturation or highly magnetic materials near the orbit. Protocol errors may cause artifacts such as saturation, phase wraparound, truncation, shading, and partial-volume artifacts. This information can be used to improve orbital image quality and avoid misinterpretation of image artifacts. Use of fat saturation, silicone saturation, and careful patient screening for metal near the eyes and instruction to reduce motion can help reduce the occurrence of artifacts. In addition, optimal imaging technique is essential and should include use of proper surface coils, plane of section, and pulse sequences.


Quantitative muscle ultrasound measures rapid declines over time in children with SMA type 1.
Muscles are small in spinal muscular atrophy (SMA). It is not known if muscle size changes over time in SMA type 1. We quantified changes over time in muscle size and echointensity during two repeated ultrasound examinations of unilateral proximal (biceps brachii/brachialis and quadriceps) and distal (anterior forearm flexors and tibialis anterior) muscles in three children with SMA type 1. We compared muscle thickness (MT) to body weight-dependent normal reference values. Children were 1, 6, and 11months old at baseline and had 2, 2 and 4 months between ultrasound examinations, respectively. At baseline, MT was normal for weight in all muscles except an atrophic quadriceps in the oldest child. MT decreased and echointensity increased (worsened) over time. At follow up, MT was below normal for weight in the quadriceps in all three children, in the biceps/brachioradialis in two, and in the anterior forearm in one. Tibialis anterior MT remained normal for weight in all three children. Muscle echointensity increased over time in all muscles and, on average, more than doubled in two children. In children with SMA type 1, muscle atrophies and becomes hyperechoic over time. Quantitative muscle ultrasound measures disease progression in SMA type 1 that warrants additional study in more children.


Dural sinus thrombosis presenting three months postpartum.
Dural sinus thrombosis is a rare complication of pregnancy and the puerperium. We report a case of dural sinus thrombosis that presented as a persistent headache and then a new-onset seizure in a previously healthy 28-year-old woman 3 months postpartum. Subtle changes consistent with sinus thrombosis were present on noncontrast computed tomography, but magnetic resonance venography ultimately confirmed the diagnosis. Anticonvulsant and anticoagulant therapy were initiated and maintained, and the patient recovered completely. Follow-up genetic analysis revealed heterozygosity for the Factor II 20210A variant of the prothrombin gene mutation.


PREVALENCE, KNOWLEDGE AND PREVENTIVE PRACTICES AGAINST HYPERTENSION AMONG POLICE OFFICERS IN IBADAN.
Hypertension is a major global health problem. Armed forces personnel are at increased risk of hypertension due to the nature of their occupation as early responders. There is dearth of data on knowledge and prevalence of hypertension among police officers in Ibadan, Nigeria. This study was conducted to address this gap in knowledge. A total of 170 police officers participated in the study. A questionnaire was used to document demographic profile, knowledge and practices to prevent hypertension. Abdominal circumference and blood pressure were measured among study participants. A digital Omron HEM 8712 blood pressure monitor was used to assess BP and a non-stretchable measuring tape was used to determine waist circumference. Hypertension was assessed by ≥140/90 mmHg and abdominal obesity by ≥80cm for female and ≥94cm for male. Mean age of respondents was 36.7±8.4 years; more than half (64.7%) were males. Majority (47.6%) had fair knowledge of hypertension. The prevalence of abdominal obesity and hypertension were 51.7% and 17.5% respectively. About a tenth (11.4%) were both hypertensive and obese. More females than males' respondents had abdominal obesity (p=0.00); while more males (19.3%) than females (14.0%) were hypertensive (p=0.39). About two-third (68.2%) reported involvement in unhealthy preventive practices including consumption of alcohol, foods high in salt and fat content, and tobacco smoking. Older, married and senior officers were significantly at higher risk of being hypertensive than younger, never married, and junior officers. Police officers have adequate knowledge of hypertension, but many in this group are hypertensive. Clinical and educational interventions are recommended to address the problem.


Rhesus enteric calicivirus surrogate model for human norovirus gastroenteritis.
Human noroviruses are one of the major causes of acute gastroenteritis worldwide. Due to the lack of an efficient human norovirus cell culture system coupled with an animal model, human norovirus research mainly relies on human volunteer studies and surrogate models. Current models either utilize human norovirus-infected animals including the gnotobiotic pig or calf and the chimpanzee models, or employ other members of the family Caliciviridae including cell culture propagable surrogate caliciviruses such as the feline calicivirus, murine norovirus and most recently the Tulane virus. One of the major features of human noroviruses is their extreme biological diversity, including genetic, antigenic and histo-blood group antigen binding diversity, and possible differences of virulence and environmental stability. This extreme biological diversity and its effect on intervention/prevention strategies cannot be modelled by uniform groups of surrogates, much less by single isolates. Tulane virus, the prototype recovirus strain, was discovered in 2008. Since then, several other novel recoviruses have been described and cell culture adapted. Recent studies indicate that the epidemiology, the biological features and diversity of recoviruses and the course of infection and clinical disease in recovirus-infected macaques more closely reflect those properties of human noroviruses than any of the current surrogates. This review aims to summarize what is currently known about recoviruses, highlight their biological similarities to human noroviruses and discuss applications of the model in addressing questions relevant for human norovirus research.


Magnetic resonance imaging of ulnar nerve abscess in leprosy: a case report.
A 14-year-old girl on multidrug treatment for borderline tuberculoid leprosy presented with a swelling in her left arm and soon thereafter developed ulnar claw hand. MRI showed a well-defined ovoid lesion arising from the left ulnar nerve, isointense to muscle on T1W images and hyperintense on T2W and STIR images. On post gadolinium T1W sequence the lesion showed peripheral rim enhancement with central necrosis suggestive of abscess. The ulnar nerve proximal and distal to the lesion was thickened and showed mild contrast enhancement. On aspiration the swelling yielded frank pus which was positive for acid-fast bacilli.


Why consumers need more protection against claims for dietary supplements and herbs.
Federal agencies have never had enough resources to cope with the enormous amount of deception in the supplement and health-food marketplace. Passage of the 1994 Dietary Supplement Health and Education Act (DSHEA) has worsened the situation by encouraging dubious claims and weakening the Food and Drug Administration (FDA)'s ability to ban dangerous products.


Association Between ADHD and COVID-19 Infection and Clinical Outcomes: A Retrospective Cohort Study From Electronic Medical Records.
Though psychiatric illnesses have been associated with increased COVID-19 infection risk, limited information exists about the relationship between ADHD and COVID-19. Using the TriNetX COVID-19 Research Network, we examined the impact of ADHD diagnosis and treatment on COVID-19 infection rates and outcomes. ADHD patients had greater risk of COVID-19 (risk ratio (RR) 1.11, 95% CI [1.09, 1.12]). Increased risk was higher in females than males, and highest among Asian and Black patients. Within 60 days after COVID-19 diagnosis, ADHD patients had lower rates of hospitalization (RR 0.91, 95% CI [0.86, 0.96]) and mechanical ventilation (RR 0.69, 95% CI [0.58, 0.83]), and a nonsignificant reduced death rate (RR 0.65, 95% CI [0.42, 1.02]). Patients who recently received ADHD medication had higher rates of COVID-19 (RR 1.13; 95% CI [1.10, 1.15]). ADHD poses increased risk for COVID-19, but may reduce risk of severe outcomes. ADHD medications modestly impacted COVID-19 risk.


Nanoparticles for the optical imaging of tumor E-selectin.
We designed a fluorescent peptide-magnetic nanoparticle conjugate that images E-selectin expression in mouse xenograft models of Lewis lung carcinoma (LLC) by fluorescence reflectance imaging. It was synthesized by attaching the E-selectin-binding peptide (ESBP; CDSDSDITWDQLWDLMK) to a CLIO(Cy5.5) nanoparticle to yield ESBP-CLIO(Cy5.5). Internalization by activated human umbilical vein endothelial cells (HUVECs) was rapid and mediated by E-selectin, indicated by the lack of uptake of nanoparticles bearing similar numbers of a scrambled peptide (Scram). To demonstrate the specificity of E-selectin targeting to ESBP-CLIO(Cy5.5) in vivo, we coinjected ESBP-CLIO(Cy5.5) and Scram-CLIO(Cy3.5) and demonstrated a high Cy5.5/Cy3.5 fluorescence ratio using the LLC. Histology showed that ESBP-CLIO was associated with tumor cells as well as endothelial cells, but fluorescence-activated cell sorter analysis showed a far less expression of E-selectin on LLC than on HUVECs. Using immunohistochemistry, we demonstrated E-selectin expression in both endothelial cells and cancer cells in human prostate cancer specimens. We conclude that ESBP-CLIO(Cy5.5) is a useful probe for imaging E-selectin associated with the LLC tumor, and that E-selectin is expressed not only on endothelial cells but also on LLC cells and human prostate cancer specimens.


Mental health service use among older African Americans: the National Survey of American Life.
The objective of this study was to examine mental health services utilization of older African Americans using data from the National Survey of American Life. A subsample of African American respondents aged 55 years or older (N = 837) was used for this study. Thirteen mental disorders, including mood, anxiety, and substance disorders, were assessed using the Diagnostic Statistical Manual-IV World Mental Health Composite International Diagnostic Interview. Seventy-four respondents (9.6%) met criteria for a disorder. Self-reported service use included psychiatric and nonpsychiatric mental health services, general medical care, and nonhealth care (e.g., human services and complementary-alternative medicine). Overall, 46.5% (N = 30) of older African Americans with any one 12-month disorder used some form of services in the last year; 47.2% (N = 12) with two or more disorders used any services. Those reporting any mood disorder had higher service use in every sector compared with those with any anxiety or any substance disorder. Age was significantly related with each service sector except for nonhealth care. There were no significant gender or work status differences, and marital status was only significant in nonhealth care use. Those aged 55-64, married, and not residing in the south were more likely to report any service use than their respective counterparts. These findings reveal that a significant proportion of African American older adults with mental health disorders do not receive professional help. Future research on system, provider, and patient factors is needed to clarify and explain underutilization of mental health services.


A simple method for relative assessment of the sound propagation velocity in breast tumors: technique and diagnostic efficacy.
The purpose of this study was to describe and evaluate a method for assessing the sound propagation velocity in breast tumors relative to the velocity in adjacent tissue. Sixty-six patients with palpable breast tumors were studied. The scanning plane was aligned so that it transected the tumor and depicted the front of a rib or the pleura-lung interface behind the tumor. This contour was evaluated for distortion, and the height of the distortion and the height of the tumor were used to calculate the relative sound propagation velocity. A posterior reference line was revealed behind 62 of 66 tumors. Of these 62 tumors, an elevation was seen behind 49 tumors, and no distortion was seen behind 13 tumors. A depression was never observed. The median relative sound propagation velocity of 1.07 that was calculated in 42 carcinomas (range, 1.00-1.14) was insignificantly higher (p = .079) than the median relative sound propagation velocity of 1.04 obtained in 20 fibroadenomas (range, 1.00-1.15). Although assessment of relative sound propagation velocity in breast tumors was successful, the relative velocities differed only insignificantly between benign and malignant lesions.


[Analysis and application of SNP and haplotype in the human genome].
Single nucleotide polymorphism (SNP) is the most common type of genetic variant in human genome. Haplotype, defined as a specific set of alleles observed on a single chromosome, or a part of a chromosome,has been an integral part of human genetics for decades. The goal of the international HapMap project is to determine the common patterns of DNA sequence variation and find the Tag SNPs representing all SNPs in the human genome. Some studies demonstrated that the analyses of haplotype defined by the grouping and interaction of several variants rather than any individual SNP correlated with complex phenotypes. Here, we describe the definitions of SNPs, genotype, haplotype and some information of the HapMap project. In this review, we summarize the current three haplotype-inference methods, including Clark' method, EM algorithm and Byes approach, and the different defining methods for haplotype block, as well as the methods for choosing tag SNPs and association studies of complex diseases using haplotype. The major public SNP databases and applications of SNPs and haplotype in common complex diseases and drug response are also introduced in the paper.


The Use of an Indwelling Catheter Protocol to Reduce Rates of Postoperative Urinary Tract Infections.
Catheter-associated urinary tract infections (CAUTI) have been associated with increases in morbidity and mortality as well as increased costs of hospitalization. At our institution, we implemented a protocol for indwelling catheter use, maintenance, and removal based on Center for Medicare and Medicaid Services (CMS) guidelines, in efforts to reduce CAUTI rates. A hospital committee of quality stewards focused on several measures which included staff education, modification of existing systems to ensure compliance, and auditing of patient care areas for catheter utilization before implementation of the protocol. Pre- and postintervention postoperative cohorts were then identified through American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) for prevalence of CAUTI. Data were collected through chart review and postdischarge patient interviews. A total of 3873 patients were identified between September 2007 and December 2010. Thirty-six patients (2.6%) were diagnosed with a CAUTI in the preintervention group (N = 1404) compared to 38 (1.5%) patients who were diagnosed with a CAUTI in the postintervention group (N = 2469). There was a 1.1% decrease in CAUTI rate after protocol implementation (P < .028). This reduction in rates resulted in annual estimated savings of $81,840 to $320,540 annually. A simple, multifaceted approach consisting of staff education and changing existing processes to reflect best care practices has the potential to significantly reduce the incidence of postoperative CAUTI.


Remote sensing image segmentation based on a robust fuzzy C-means algorithm improved by a parallel Lévy grey wolf algorithm.
Due to the insufficient use of local information, the traditional fuzzy C-means (FCM) algorithm and its extension algorithm combined with spatial information show poor robustness and low segmentation accuracy. In addition, in the process of image segmentation based on the FCM algorithm, the initial center estimation is regarded as the process of searching the appropriate value in the gray range. To solve these problems, a new robust algorithm is proposed in this paper. The algorithm searches the optimal initial center by introducing an improved parallel Lévy grey wolf optimization algorithm, which is an improved fuzzy C-means segmentation algorithm that combines local information and adaptive gray weighting. Experimental results infer that both the precision and efficiency of the proposed method are superior to those of the state-of-arts.


[Standardized surgical procedure of conformal sphincter-preservation operation for low rectal cancer (2023 edition)].
Conformal sphincter-preservation operation (CSPO) is considered the effective surgical technique for preserving the sphincter in cases of low rectal cancer. Accurate preoperative diagnosis and staging, reasonable selection of surgical approaches and technique, standardized perioperative management, and postoperative rehabilitation are the keys to ensuring the oncological clearance and functional preservation of CSPO. However, there is currently a lack of standardized surgical procedure for implementing CSPO in China. Therefore, the Colorectal Surgery Group of Surgery Branch of the Chinese Medical Association,along with the Colorectal Cancer Committee of the Chinese Medical Doctor Association and the Anorectal Branch of Chinese Medical Doctor Association, gathered experts in colorectal surgery to discuss and establish this standardized surgical procedure of CSPO. This standard, based on the latest evidence from literature, expert experiences, and China national condition, focuses on the definition, classification, pelvic anatomy, surgical techniques, postoperative complications, and perioperative care of CSPO. It aims to guide the standardized clinical practice of CSPO in China.


TWIST2 demonstrates differential methylation in immunoglobulin variable heavy chain mutated and unmutated chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease for which natural history can be predicted based on the presence or absence of immunoglobulin (Ig) variable heavy chain (V(H)) gene mutations. Herein we report selective epigenetic silencing of the transcription factor TWIST2 (DERMO1) in Ig V(H) mutated CLL and describe a semiquantitative assay to study promoter methylation of this gene in primary tumor cells. TWIST2 promoter methylation was identified by restriction landmark genome scanning. Southern blot (SB), bisulfite sequencing, and combined bisulfite restriction analysis (COBRA), and quantitative SB-COBRA was performed to study methylation of the TWIST2 promoter. Reverse transcription polymerase chain reaction assays were used to study TWIST2 expression in CLL cells. Following identification and confirmation of TWIST2 methylation in CLL patients, we demonstrated that expression of this transcription factor is related to the degree of promoter methylation. Expression of TWIST2 in a CLL cell line in which the promoter is methylated was increased following decitabine treatment. We next studied 53 patients by COBRA and demonstrated that 72% of patient samples with mutated Ig V(H) show TWIST2 methylation, while only 16% of patient samples with unmutated Ig V(H) were methylated (P < .001). In a subset of patients, methylation of TWIST2 correlated with mRNA expression. TWIST2 is differentially methylated in CLL cells relative to Ig V(H) mutational status and can be quantitatively monitored by SB-COBRA. Based on the known role of TWIST2 in silencing p53 function in other malignancies, future studies should focus on the role of TWIST2 in CLL and related lymphoproliferative diseases.


Ultrasound guidance: technique and results of aggressive ultrasound-guided PTCA. The UPSIZE Pilot Trial.
Stenting results in a larger lumen than conventional balloon angioplasty. This is the major determinant of a good acute and long-term result. In this non-randomised, single centre trial, intravascular ultrasound was used preinterventionally to guide the choice of the balloon size. The aim was to achieve a maximum lumen area with balloon angioplasty only. We included 346 patients with 360 lesions. The diameter of the external elastic lamina by intravascular ultrasound was 4.67 mm. A mean balloon size of 4.0 mm was chosen. The initial luminal gain was 1.82 mm, the lumen area post intervention was 6.6 mm(2). Dissections occurred frequently but the incidence of major adverse events was not increased. At one year follow-up, the overall event free survival was 81%. Target lesion revascularisation was performed in 34 patients (10%). An angiographic follow-up was available for 261 patients (76%). Restenosis (> 50% diameter Stenosis) was found in 21%. The results show, that ultrasound guidance of balloon angioplasty provides a means to achieve a large initial luminal gain without the routine use of stents. The acute and long-term results suggest that the approach is safe and efficient. The data compare favorably with similar studies using advanced intravascular diagnostic tools to guide the angioplasty procedure.


Dual targeting of hepatocyte DGAT2 and stellate cell FASN alleviates nonalcoholic steatohepatitis in mice.
Nonalcoholic steatohepatitis (NASH) is a malady of multiple cell types associated with hepatocyte triglyceride (TG) accumulation, macrophage inflammation, and stellate cell-induced fibrosis, with no approved therapeutics yet available. Here, we report that stellate cell fatty acid synthase (FASN) in de novo lipogenesis drives the autophagic flux that is required for stellate cell activation and fibrotic collagen production. Further, we employ a dual targeting approach to NASH that selectively depletes collagen through selective stellate cell knockout of FASN (using AAV9-LRAT Cre in FASNfl/fl mice), while lowering hepatocyte triglyceride by depleting DGAT2 with a GalNac-conjugated, fully chemically modified siRNA. DGAT2 silencing in hepatocytes alone or in combination with stellate cell FASNKO reduced liver TG accumulation in a choline-deficient NASH mouse model, while FASNKO in hepatocytes alone (using AAV8-TBG Cre in FASNfl/fl mice) did not. Neither hepatocyte DGAT2 silencing alone nor FASNKO in stellate cells alone decreased fibrosis (total collagen), while loss of both DGAT2 plus FASN caused a highly significant attenuation of NASH. These data establish proof of concept that dual targeting of DGAT2 plus FASN alleviates NASH progression in mice far greater than targeting either gene product alone.


Developing leaders vs training administrators in the health services.
In these difficult times, health care institutions need leaders, not simply managers. Leaders' breadth of skills and perspective come from understanding the values involved in health care delivery; managers know the right way to do things, but leaders know which are the right things to do. Schools of public health are moving away from their potential contribution to leadership development in health services administration. The result is a lack of accountability to the community. Leadership skills and an examination of values should be part of health services administration programs in schools of public health, which should see their mission as helping to identify and train leaders, not simply technical specialists in management.


Effect of oestradiol on the secretory immune system in the rat: an increase in biliary IgM antibodies against a T-cell independent antigen.
The effect of sex hormones on the secretory immune system was studied in rats ooforectomized and substituted with oestradiol in permeable capsules deposited subcutaneously. Ooforectomized rats and sham-operated rats without oestradiol substitution served as controls. Two weeks after the ooforectomy the rats were immunized in the Peyer's patches with Escherichia coli O6 carrying type 1 fimbriae. Some rats were given a booster dose with the same antigen at the same site 3 weeks later. Bile and serum were taken 7 days after the last immunization. The oestradiol treatment did not influence the total level of IgA or IgG or the level of specific IgA or IgG antibodies in bile or serum. Instead there was a specific increase in biliary IgM antibodies against lipopolysaccharide (LPS) as well as a rise in the total IgM concentration in the bile in the oestradiol-treated rats. Despite this there was no difference in the biliary IgM anti-fimbrial antibody level between the different groups. The oestradiol treatment did not change the levels of total immunoglobulins or antibodies against fimbriae and LPS in serum. An oestradiol-induced increase similar to the one seen in biliary IgM anti-LPS antibodies in primary immunized animals was not seen during the secondary response in booster immunized rats. Thus it seemed as if the effect of oestradiol on the secretory immune system in the bile was mainly due to an influence on primary stimulated B-cell clones in the liver, producing IgM antibodies against a T-cell-independent antigen. The effect may be mediated through a direct action of oestradiol on the B lymphocytes.


Rapid influences of cued visual memories on attentional guidance.
There is evidence that the deployment of attention can be biased by the content of visual working memory. Recently, it has been shown that focusing internal attention to a specific item in memory not only increases the accessibility of that specific item for retrieval, but also results in increased attentional guidance toward matching external stimuli by that item. Here, we investigated the time course of attentional guidance by cued memories. Following a retro-cue that prioritized one of two memory items, participants performed a visual search task. The interval between the cue and the search display was varied. Consistent with earlier findings, we observed memory-related capture when the search display contained a distractor that was related to the cued item in memory. No such effects were found for the uncued items or when none of the memory items were prioritized by a retro-cue. Results suggest that the prioritization by a retro-cue is a very rapid process that starts to affect perceptual selection within the first 100-200 ms following the cue.


Efficacy of a nicotine lozenge for smoking cessation.
Since nicotine gum was introduced in the 1980s, nicotine replacement therapy has become the most widely used pharmacological smoking cessation treatment. Some smokers prefer acute oral forms, but many smokers reject chewing gum. We tested the safety and efficacy of a new nicotine polacrilex lozenge for smoking cessation. Double-blind, placebo-controlled, randomized clinical trial with parallel arms testing 2- and 4-mg nicotine lozenges. Smokers (n = 1818) were assigned to a lozenge dose on the basis of nicotine dependence, assessed by time to the first cigarette of the day. Low-dependence smokers were randomized to receive the 2-mg nicotine (n = 459) or placebo (n = 458) lozenge; high-dependence smokers, the 4-mg nicotine (n = 450) or placebo (n = 451) lozenge. We assessed abstinence at 6, 12, 24, and 52 weeks and analyzed craving and withdrawal symptoms. Treatment with the nicotine lozenge resulted in significantly greater 28-day abstinence at 6 weeks, for the 2-mg (46.0% vs. 29.7%; odds ratio [OR], 2.10; 95% confidence interval [CI], 1.59-2.79; P<.001) and the 4-mg (48.7% vs. 20.8%; OR, 3.69; 95% CI, 2.74-4.96; P<.001) lozenges, compared with placebo. Significant treatment effects were maintained for a full year. Smokers who used more lozenges achieved significantly better treatment effects. Use of the active lozenge also resulted in reduced craving and withdrawal. Most adverse events were moderate and resembled those seen with nicotine gum. The nicotine lozenge is a safe and effective new treatment for smoking cessation in low- and high-dependence smokers.


Ternary NiCeCo-Layered Double Hydroxides Grown on CuBr2@ZIF-67 Nanowire Arrays for High-Performance Supercapacitors.
Ternary layered double-hydroxide-based active compounds are regarded as ideal electrode materials for supercapacitors because of their unique structural characteristics and excellent electrochemical properties. Herein, an NiCeCo-layered double hydroxide with a core-shell structure grown on copper bromide nanowire arrays (CuBr2@NCC-LDH/CF) has been synthesized through a hydrothermal strategy and calcination process and utilized to fabricate a binder-free electrode. Due to the unique top-tangled structure and the complex assembly of different active components, the prepared hierarchical CuBr2@NCC-LDH/CF binder-free electrode exhibits an outstanding electrochemical performance, including a remarkable areal capacitance of 5460 mF cm-2 at 2 mA cm-2 and a capacitance retention of 88% at 50 mA cm-2 as well as a low internal resistance of 0.163 Ω. Moreover, an all-solid-state asymmetric supercapacitor (ASC) installed with CuBr2@NCC-LDH/CF and activated carbon electrodes shows a high energy density of 118 Wh kg-1 at a power density of 1013 W kg-1. Three assembled ASCs connected in series can operate a multifunctional display for over three and a half hours. Therefore, this innovative work provides new inspiration for the preparation of electrode materials for supercapacitors.


Pharmacotherapy for post-traumatic stress disorder.
PTSD is a common disorder with high comorbidity and a tendency toward chronicity, which responds slowly to treatment and, in many patients, may not totally resolve even with long-term treatment. For most persons with PTSD, a combined approach to treatment is beneficial, at least in the acute stages of the illness. Pharmacotherapy is an important component of treatment during the acute stages of the illness and may be necessary on a long-term basis for many patients. Because the data from controlled trials of pharmacotherapy are limited, it is not possible to present a unified approach or develop a consensus that is well supported by research findings. What has emerged from the available data is that antidepressants, particularly those with serotoninergic properties, are helpful for core PTSD symptoms when given at higher dose levels for at least 5 to 8 weeks. The TCAs as a group appear to be effective in amelioration of the intrusive symptoms and of anxiety and depressive symptoms, while having little effect on avoidance symptoms. Initial data from studies of the SSRIs suggests that they may have greater efficacy than other drugs in the treatment of avoidance and numbing symptoms and may effect enough overall global improvement in PTSD symptoms that some patients will no longer meet the diagnostic criteria. The hyperarousal symptoms may respond somewhat to antidepressants, but should symptoms continue to be disabling, buspirone or benzodiazepines may be indicated. In choosing a benzodiazepine, those less likely to have distressing withdrawal symptoms, such as clonazepam and chlordiazepoxide, should be considered. Clonazepam, with its serotoninergic properties, may prove to be a particularly efficacious drug. For some patients, phenelzine may be a good choice because it has proven efficacy for the intrusive PTSD symptoms, for depressive symptoms, and for some symptoms of autonomic arousal, such as panic attacks. Other agents to be considered for alleviation of hyperarousal symptoms are lithium, anticonvulsants, and clonidine. In addressing the symptoms of poor impulse control, lithium, beta-blocking drugs, and carbamazepine may be helpful. Brief psychotic episodes should respond to a neuroleptic, although psychoticlike dissociative spells may be nonresponsive.


Occupational health in South Korea.
The government-initiated Annual Workers Health Examination Program and the Industrial Accident Compensation Program both of which are delivered from outside the workplace mainly by a handful of service agents have remained the cornerstones of occupational health and safety (OHS) policy in South Korea since the 1960s. Initially, policies centered on the technical dimensions of OHS problems. This acultural approach is no longer efficient, and the scope of problems that can be dealt with is limited. The injury rate has gone down from 6 to less than 1 injury per 100 insured workers, but since the 1980s there has been no sign of improvement in the death rate from industrial accidents, and future improvement in the injury rate is not expected. As South Korea is facing major economic and social changes, review of current OHS policy is also underway. International collaborations and comparisons will surely add thoughtful perspectives to this discussion.


Comparison of outcomes between a less experienced surgeon using a fully endoscopic technique and a very experienced surgeon using a microscopic transsphenoidal technique for pituitary adenoma.
The comparative efficacy of microscopic and fully endoscopic transsphenoidal surgery for pituitary adenomas has not been well studied despite the adoption of fully endoscopic surgery by many pituitary centers. The influence of surgeon experience has also not been examined in this setting. The authors therefore compared the extent of tumor resection (EOR) and the endocrine outcomes of 1 very experienced surgeon performing a microscopic transsphenoidal surgery technique with those of a less experienced surgeon using a fully endoscopic transsphenoidal surgery technique for resection of nonfunctioning pituitary adenomas in a concurrent series of patients. Post hoc analysis was conducted of a cohort of adult patients prospectively enrolled in a pituitary adenoma quality-of-life study between October 2011 and June 2014. Patients were followed up for 6 months after surgery. Patients were treated either by a less experienced surgeon (100 independent cases) who practices fully endoscopic surgery exclusively or by a very experienced surgeon (1800 independent cases) who practices microscopic surgery exclusively. Patient demographic characteristics, tumor characteristics, hypopituitarism, complications, and length of hospital stay were analyzed. Tumor volumes and EOR were determined by formal volumetric analysis involving manual segmentation of MR images performed before surgery and within 6 months after surgery. Logistic regression analysis was used to determine predictors of EOR. Fifty-five patients underwent fully endoscopic transsphenoidal surgery, and 80 patients underwent fully microscopic transsphenoidal surgery. The baseline characteristics of the 2 treatment groups were well matched. EOR was similar between the endoscopic and microscopic groups, respectively, as estimated by gross-total resection rate (78.2% vs 81.3%, p = 0.67), percentage of tumor resected (99.2% vs 98.7%, p = 0.42), and volume of residual tumor (0.12 cm(3) vs 0.20 cm(3), p = 0.41). Multivariate modeling suggested that preoperative tumor volume was the most important predictor of EOR (p = 0.001). No difference was found in the development of anterior gland dysfunction (p > 0.14), but there was a higher incidence of permanent posterior gland dysfunction in the microscopic group (p = 0.04). Combined rates of major complications and unplanned readmissions were lower in the endoscopic group (p = 0.02), but individual complications were not significantly different. A less experienced surgeon using a fully endoscopic technique was able to achieve outcomes similar to those of a very experienced surgeon using a microscopic technique in a cohort of patients with nonfunctioning tumors smaller than 60 cm(3). The study raises the provocative notion that certain advantages afforded by the fully endoscopic technique may impact the learning curve in pituitary surgery for nonfunctioning adenomas.


A structural, kinetic model of soft tissue thermomechanics.
A structure-based kinetic model was developed to predict the thermomechanical response of collagenous soft tissues. The collagen fibril was represented as an ensemble of molecular arrays with cross-links connecting the collagen molecules within the same array. A two-state kinetic model for protein folding was employed to represent the native and the denatured states of the collagen molecule. The Monte Carlo method was used to determine the state of the collagen molecule when subjected to thermal and mechanical loads. The model predictions were compared to existing experimental data for New Zealand white rabbit patellar tendons. The model predictions for one-dimensional tissue shrinkage and the corresponding mechanical property degradation agreed well with the experimental data, showing that the gross tissue behavior is dictated by molecular-level phenomena.


Development of ultraporous fired bricks as support for yeast cell immobilization.
Ultraporous fired bricks (porosities from 56 to 72%) were developed from materials locally available in Nigeria. The grog particle size was used to modulate the porosity of the bricks. The porous bricks produced were then employed as supports for the immobilization of a yeast strain isolated from a local alcoholic beverage, palm wine. The influence of a brick's porosity and particle size on the cell-loading capacity and cell growth inside the fired brick support were studied. The study revealed that a brick's porosity varied linearly with the mean particle size of the grog, increasing from a porosity of 56% at a particle size of 0.805 mm to 72% at a particle size of 0.075 mm. Cell saturation of the surface area available within the support matrix was completed within four hours of contact between the cell and the adsorbing surface especially for the most porous samples. Cell growth was therefore not observed in such cases; however, the less porous samples supported some cell growth upon incubation. Cell holdup was also observed to increase exponentially when either the porosity was increased or the particle size was decreased. The influence of particle size, however, became insignificant at very high porosities.


[Autoimmune chronic active hepatitis].
On the basis of a literature review the modern views on the aetiology, clinical features and treatment of autoimmune chronic hepatitis are presented. An appropriate diagnosis is of importance as the autoimmune disease is responsive to corticosteroids, and may be aggravated by interferon, nowadays given for virus-induced liver disease.


Reconstruction of complex midfacial defects.
Modern treatment of complex midfacial defects has evolved over the past 5 years, primarily with the advent of reliable vascularized bone flaps and osseointegrated implants. To determine the effectiveness of these advances, 26 consecutive patients with complex midfacial defects treated from 1991 through 1995 with immediate muscle-flap coverage were evaluated. The etiology of the defect included neoplasm (n = 23) and trauma (n = 3). Seventy-eight percent of the patients received adjuvant radiation therapy. Follow-up ranged from 3 months to 4 years, with a mean of 18 months. Twenty-three patients (88 percent) were reconstructed with a single major procedure. All patients had free-flap reconstruction, and 100 percent of the flaps survived. Late tumor recurrence was seen in 5 of 23 patients (22 percent) and was detected promptly. Aesthetic and functional results were rated good or excellent in 77 and 88 percent of the patients, respectively, as determined by patient questionnaires and physical examinations. Fourteen of 18 patients (78 percent) undergoing partial or complete alveolar ridge resection received dental rehabilitation, 43 percent of whom received osseointegrated implants into either a bone flap or remaining native bone. Osseointegrated implants were inset during the initial reconstruction 50 percent of the time. A treatment algorithm for free-flap selection based on the size of the defect and the bony requirement for reconstruction is presented. Bony restoration is only required in those areas where osseointegrated implants need to be placed. In such cases, the fibula osteocutaneous free flap is the flap of choice. Otherwise, soft-tissue flaps are selected based on wound size. Immediate free-flap coverage provides effective, single-stage treatment, both aesthetically and functionally, for complex midfacial defects.


[A clinical study of bladder stone with spinal cord injury in subacute stage].
Bladder stones that form in patients with spinal cord injury in the subacute stage can cause significant morbidity. In this retrospective study, we investigated the factors associated with bladder stone formation. The study population consisted of 141 men and 24 women (median age: 59 years) who were admitted to our hospital for rehabilitation, from January 2005 to December 2006. We investigated urinary pH, bacterial species in urine and duration of indwelling urethral catheter in the acute stage after spinal cord injury. Thirty-one patients (16.3%) were diagnosed with bladder stones and underwent transurethral lithotripsy. Compared with patients without bladder stones, the duration of the indwelling catheter was longer in patients who bladder stones, but there was no difference between the two groups regarding urinary pH and the bacterial species found in urine. None of the patients for whom the duration of the indwelling catheter was less than a month developed bladder stones. These results suggest that long duration of the indwelling urethral catheter is a risk factor for the development of bladder stones. This information should be taken into account to reduce the occurrence of bladder stones and patients' morbidity.


Infrared spectroscopy of human tissue. IV. Detection of dysplastic and neoplastic changes of human cervical tissue via infrared microscopy.
Infrared absorption spectra of formalin-fixed, paraffin-embedded human cervical tissue are reported for normal, dysplastic and neoplastic samples. The spectral differences found in this study between these states of the tissues are far less than those observed for single cells by us and others. Nevertheless, we find a direct correspondence between spectral data from tissue sections, obtained from biopsies, and individual exfoliated cells, typically obtained during a pap procedure. We also find that spectra due to dysplastic samples fall about halfway between the spectral features of normal and cancerous samples.


A novel signal acquisition platform of human cardiovascular information with noninvasive method.
Cardiovascular diseases (CVDs) are considered the major cause of death worldwide, so more researchers pay more and more attention to the development of a non-invasive method to obtain as much cardiovascular information (CVI) as possible for early screening and diagnosing. It is known that considerable brain information could be probed by a variety of stimuli (such as video, light, and sound). Therefore, it is quite possible that much more CVI could be extracted via giving the human body some special interrelated stimulus. Based on this hypothesis, we designed a novel signal platform to acquire more CVI with a special stimulus, which is to give a gradual decrease and a different settable constant pressure to six air belts placed on two-side brachia, wrists, and ankles, respectively. During the stimulating process, the platform is able to collect 24-channel dynamic signals related with CVI synchronously. Moreover, to improve the measurement accuracy of signal acquisition, a high precision reference chip and a software correction are adopted in this platform. Additionally, we have also shown some collection instances and analysis results in this paper for its reliability. The results suggest that our platform can not only be applied on study in a deep-going way of relationship between collected signals and CVDs but can also serve as the basic tool for developing a new noninvasive cardiovascular function detection instrument and system that can be used both at home and in the hospital.


Developing a medical humanities concentration in the medical curriculum at the University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
To the author's knowledge, the University of Rochester School of Medicine and Dentistry is the only medical school in the United States that offers a concentration or minor in medical humanities for medical students. This article presents how the author first thought of offering a concentration in medical humanities and explains the educational elements students must satisfy. In 1998, the university underwent a major curriculum revision, dubbed the "double-helix" curriculum because of its goal of intertwining basic science and clinical medicine over all four years of medical school. As course director of the Medical Humanities Seminars for more than ten years, the author saw this change as an opportunity to expand the humanities curriculum. The number of sessions and courses offered in the first two years doubled as part of the transition to the new curriculum. In addition, the author proposed to the medical school curriculum steering committee to approve a concentration in clinical ethics and humanities. The concentration option motivates students to continue to pursue their humanistic interests in the third and fourth years of medical school. About 25% of the student body has signed up in the first two years the concentration has been available.


Radical Silyldifluoromethylation of Electron-Deficient Alkenes.
A reaction of bromo- and iododifluoromethyl-substituted silanes with electron-deficient alkenes in the presence of an N-heterocyclic carbene borane complex is described. The reaction is performed under irradiation with light-emitting diodes and proceeds via a radical chain mechanism. The resulting products, the functionalized silicon reagents, can undergo chemoselective transformations involving either the silyldifluoromethyl fragment or the functional group.


Influence of frailty syndrome on patient prognosis after coronary artery bypass grafting.
Frailty syndrome and cardiovascular diseases are closely related because of the shared physiological pathway of chronic, low-intensity inflammation. Frailty syndrome may be an adverse factor in the prognosis of patients with cardiovascular disease (CVD). To assess the influence of frailty syndrome on patient prognosis after coronary artery bypass grafting (CABG). The study was conducted at the Clinic of Cardiac Surgery in Katowice and involved 180 patients (56 women, 31.11%) over 60 years of age who qualified for CABG surgery. The Tilburg Frailty Indicator (TFI) was used to assess frailty syndrome and the The World Health Organization Quality of Life Brief Version (WHOQOL-BREF) questionnaire was used to assess quality of life. Statistical analysis was performed using R software. Frailty syndrome was diagnosed in 42 patients (23.3%), including 24 men and 18 women. More than 1/3 of patients had complications during or after surgery, including 34.6% of patients without frailty syndrome and 28.6% of patients with frailty features. All of the complications occurred in 57 (31.6%) patients. Early complications accounted for 89.5% of all events - 93.3% of which occurred in patients without frailty syndrome and 75% in patients with frailty features (p = 0.289). More than 1/3 of patients experienced complications during or after the CABG procedure. Early postoperative complications accounted for almost all of the adverse events in patients with frailty. However, frailty syndrome was a poor predictor of rehospitalization.


Trends in healthcare use in the New York City region following the Terrorist Attacks of 2001.
In 2001, terrorism led to emotional stress, disruptions in adherence to treatments and access to services, and exposure to environmental contaminants in New York City (NYC). To describe healthcare use following the terrorist attacks of 2001, we examined insurance claims for January 2000 to March 2002 among more than 2 million residents of the NYC region who were enrolled in the health plans of a large insurer, including overall use by care setting and use for selected conditions that may be associated with stress or other disaster consequences. For all enrollees and for those residing at varying distances from the World Trade Center (WTC), we compared observed use to expected use, based on comparable intervals in prior years and adjusted for seasonal and secular trends. Use declined across all care settings in the 3 weeks following September 11. From October 1 to December 31, 2001, outpatient visits rose beyond expected both overall and for specific cardiovascular, gastrointestinal, and dermatologic conditions. Declines in overall mental health service use began immediately after September 11 and were sustained through March 2002. Changes in healthcare use were more marked among those residing within 10 miles of the WTC than those residing at greater distances. A transient decline in visits across all settings occurred immediately after September 11, followed by a sustained increase in demand for health care for conditions that may be associated with stress or other disaster consequences.


Evidence of the receptor-mediated influence of melatonin on pancreatic glucagon secretion via the Gαq protein-coupled and PI3K signaling pathways.
Melatonin has been shown to modulate glucose metabolism by influencing insulin secretion. Recent investigations have also indicated a regulatory function of melatonin on the pancreatic α-cells. The present in vitro and in vivo studies evaluated whether melatonin mediates its effects via melatonin receptors and which signaling cascade is involved. Incubation experiments using the glucagon-producing mouse pancreatic α-cell line αTC1 clone 9 (αTC1.9) as well as isolated pancreatic islets of rats and mice revealed that melatonin increases glucagon secretion. Preincubation of αTC1.9 cells with the melatonin receptor antagonists luzindole and 4P-PDOT abolished the glucagon-stimulatory effect of melatonin. In addition, glucagon secretion was lower in the pancreatic islets of melatonin receptor knockout mice than in the islets of the wild-type (WT) control animals. Investigations of melatonin receptor knockout mice revealed decreased plasma glucagon concentrations and elevated mRNA expression levels of the hepatic glucagon receptor when compared to WT mice. Furthermore, studies using pertussis toxin, as well as measurements of cAMP concentrations, ruled out the involvement of Gαi- and Gαs-coupled signaling cascades in mediating the glucagon increase induced by melatonin. In contrast, inhibition of phospholipase C in αTC1.9 cells prevented the melatonin-induced effect, indicating the physiological relevance of the Gαq-coupled pathway. Our data point to the involvement of the phosphatidylinositol 3-kinase signaling cascade in mediating melatonin effects in pancreatic α-cells. In conclusion, these findings provide evidence that the glucagon-stimulatory effect of melatonin in pancreatic α-cells is melatonin receptor mediated, thus supporting the concept of melatonin-modulated and diurnal glucagon release.


Prevalence of isolated minor congenital anomalies in a regional hospital in Oman.
To study the prevalence of isolated minor congenital anomalies in a regional hospital in Oman. We determined the prevalence of isolated minor congenital anomalies in 21988 births during a 10-year period from January 1993 through December 2002 by using data from the hospital-based congenital anomaly register at Nizwa Hospital, Oman. The total prevalence of congenital anomalies was 37 per 1000 births and that of minor anomalies 12.4 per 1000 births. Hypospadias, talipes deformity and polydactyly were the most common minor anomalies. A nurse or the house resident detected most of the minor anomalies soon after birth during routine neonatal examination. The study demonstrates the important contribution of minor congenital anomalies to the total prevalence of congenital anomalies. An accurate estimation of the prevalence rates of isolated minor anomalies should be possible as they are easily identifiable with minimal expertise. Case classification of congenital anomalies is important so that case groups are homogeneous and more comparable.