Advanced hypopharyngeal squamous cell carcinoma mimicking thyroid abscess in a young male: Case report and literature review.
Thyroid gland involvement by hypopharyngeal carcinoma is due to their close proximity. Initial presentation of such cancer as a thyroid abscess is rare in clinical practice thus risk of potential misdiagnosis. To the best of our knowledge, this is the first reported case in Tanzania. We present a 17-year old male who presented with difficulty in swallowing, hot potato voice, difficulty in breathing and a wound at the anterior aspect of the neck. He was managed at peripheral health facilities as having thyroid abscess so had serial incision and drainage and prescribed antibiotics. He was referred to us where he undergone tracheostomy, direct laryngoscopy coupled with taking biopsy. Computerized tomography (CT scan) of the head and neck showed an ill-defined heterogeneously enhancing mass with calcifications seen at the hypopharynx extending to the larynx and thyroid gland causing destruction of cricoid cartilage. It measured approximately 7.6 × 6.5 × 4.4 cm. The submandibular and sublingual glands are slightly infiltrated. Multiple enlarged lymph nodes are seen at anterior upper jugular IIa and posterior upper jugular IIb with the largest having central necrosis and measures approximately 2.9 × 1.7 cm. Histopathology showed an ulcerated epithelium with an infiltrative tumor containing dense chromatin. Such features were consistent with invasive squamous cell carcinoma, Grade II.(TNM staging being T4bN2cM0). The patient undergone tracheostomy to relieve upper airway obstruction and sent to oncology center for chemoradiation. Clinicians should have a high index of suspicion of a possible underlying hypopharyngeal cancer whenever encountering patients with thyroid abscess.


Differential effect of estradiol and bisphenol A on Set8 and Sirt1 expression in prostate cancer.
Exposure to estrogenic compounds has been shown to epigenetically reprogram the prostate and may contribute to prostate cancer. The goal of this study was to determine the effect of physiological doses of estradiol and bisphenol A (BPA) on the expression of histone modifying enzymes (HMEs) in prostate cancer. Using two human prostate cancer cell lines we examined the expression of Set8, a histone methyltransferase, and Sirt1, a histone deacetylase, after exposure to estrogen or BPA. These experiments were carried out in the presence of natural hormones to understand the impact of additional exposure to estrogen or BPA on HME expression. We found differential expression of the HMEs in the different models and between the different compounds. Further, we determined that the changes in gene expression occurred via estrogen receptor signaling using the ER antagonist, ICI 182,780 (fulvestrant). Interestingly we found that the combination of ICI with estrogen or BPA greatly affected the expression of Set8, even when the hormone alone had no effect. This study demonstrates that the effects of estrogen and BPA on HME expression vary and that the presence of both the estrogen receptor and androgen receptor may be important for therapeutic intervention.


Arthroscopic double-bundle anterior cruciate ligament reconstruction using autogenous quadriceps tendon.
Recently, the interest in anatomic anterior cruciate ligament (ACL) reconstruction with double-bundle technique has increased so as to reproduce the original load distribution and kinematics of the knee. We developed an arthroscopic double-bundle ACL reconstruction technique using autogenous quadriceps tendon with 2 split grafts and a patellar bone plug. The anteromedial bundle and posterolateral bundle of the ACL are replicated with each split graft of quadriceps tendon and fixed with biodegradable interference screws on the 2 femoral tunnels. The patellar bone plug of the quadriceps tendon is fixed with a biodegradable interference screw within the 1 tibial tunnel. We suggest that our technique using quadriceps tendon may be an alternative in arthroscopic double-bundle ACL reconstruction.


Real-time measurement of cytosolic free calcium concentration in HL-60 cells during static magnetic field exposure and activation by ATP.
Calcium ions are involved in a number of important signal transduction pathways in cells. Cytosolic calcium concentration ([Ca(2+)](c)) can be affected by the activation of Ca(2+) channels through the action of ligands such as ATP. The response of [Ca(2+)](c) to ligands may be affected by external factors like magnetic fields. The purpose of this study was to determine if exposure to a static magnetic field (SMF) for 800 s altered the [Ca(2+)](c) response to ATP in undifferentiated HL-60 cells. We sham exposed or field exposed fura-2 loaded HL-60 cells to a SMF of 1, 10, and 100 mT. Cells were activated with ATP 300 s into the exposure. The level of [Ca(2+)](c) was followed before, during, and after field or sham exposure with a ratiometric fluorescence spectroscopy system. It was found that high concentrations of ATP resulted in greater [Ca(2+)](c) responses, but faster recovery to near basal levels. The application of 1, 10, or 100 mT SMF did not affect the [Ca(2+)](c) response to ATP. Future work could examine the effect of a longer SMF exposure on the [Ca(2+)](c) response to ATP. Longer exposures might provide sufficient time for morphological changes in the plasma membrane to occur.


Infiltrating decidual natural killer cells are associated with spontaneous abortion in mice.
Immunohistochemistry was used to study a murine model which spontaneously aborts at a frequency of 25 to 30%. Our results show that natural killer (NK) cells are not only the predominant infiltrating cells in aborting feto-placental units, but that they also appear in a similar proportion of feto-placental units before abortion is detectable. The frequency of feto-placental units with significantly elevated NK infiltrates corresponds to the subsequent abortion frequency, indicating a causal relationship. Immunization of the mother with BALB/C splenocytes prevents these NK infiltrates and decreases the abortion frequency to normal levels. These results suggest for the first time that maternal NK cells may have an instrumental role in the etiology of spontaneous abortion.


OSCE! Variations on a theme by Harden.
In 1979, Harden described the first objective structured clinical examination (OSCE). Harden's OSCE dramatically changed the assessment of professional competence because it used actors and choreographed scenarios to evaluate the performance of professional behaviours. Because of the intense focus on performance, OSCEs have had a powerful influence on doctor training and practice. However, the immediate psychometric characteristics of OSCEs rather than their performance effects have been the subject of most research. The time has come to undertake a sophisticated sociological investigation of how OSCEs affect medical practice, including the ways in which they shape doctor interaction with patients, families and other health professionals.


Chloride Anions Regulate Kinetics but Not Voltage-Sensor Qmax of the Solute Carrier SLC26a5.
In general, SLC26 solute carriers serve to transport a variety of anions across biological membranes. However, prestin (SLC26a5) has evolved, now serving as a motor protein in outer hair cells (OHCs) of the mammalian inner ear and is required for cochlear amplification, a mechanical feedback mechanism to boost auditory performance. The mechanical activity of the OHC imparted by prestin is driven by voltage and controlled by anions, chiefly intracellular chloride. Current opinion is that chloride anions control the Boltzmann characteristics of the voltage sensor responsible for prestin activity, including Qmax, the total sensor charge moved within the membrane, and Vh, a measure of prestin's operating voltage range. Here, we show that standard narrow-band, high-frequency admittance measures of nonlinear capacitance (NLC), an alternate representation of the sensor's charge-voltage (Q-V) relationship, is inadequate for assessment of Qmax, an estimate of the sum of unitary charges contributed by all voltage sensors within the membrane. Prestin's slow transition rates and chloride-binding kinetics adversely influence these estimates, contributing to the prevalent concept that intracellular chloride level controls the quantity of sensor charge moved. By monitoring charge movement across frequency, using measures of multifrequency admittance, expanded displacement current integration, and OHC electromotility, we find that chloride influences prestin kinetics, thereby controlling charge magnitude at any particular frequency of interrogation. Importantly, however, this chloride dependence vanishes as frequency decreases, with Qmax asymptoting at a level irrespective of the chloride level. These data indicate that prestin activity is significantly low-pass in the frequency domain, with important implications for cochlear amplification. We also note that the occurrence of voltage-dependent charge movements in other SLC26 family members may be hidden by inadequate interrogation timescales, and that revelation of such activity could highlight an evolutionary means for kinetic modifications within the family to address hearing requirements in mammals.


A computational approach to determine susceptibility to cancer by evaluating the deleterious effect of nsSNP in XRCC1 gene on binding interaction of XRCC1 protein with ligase III.
Several reports suggest that non-synonymous single nucleotide polymorphisms affect the function of XRCC1 which impairs DNA repair capacity and thus increases risk to diseases like cancer. In our study, we predicted the most damaging nsSNPs using a computational approach and analysed its functional impact on the XRCC1 and LIG3 interaction. SNP rs2307166 was predicted to be deleterious using eight software programs: SIFT, PolyPhen, PANTHER, PhD-SNP, nsSNPAnalyzer, SNPS&GO, SNAP and I-Mutant. Protein structural analysis was performed using Swiss PDB viewer, and PyMOL. Xenoview was used for molecular dynamic simulation and energy minimisation. Finally, PatchDock and FireDock were used to analyse the interactions of XRCC1 and LIG3. By comparing the results we found that the mutant protein has less binding energy and the interacting amino acids than native protein. In silico analysis predicted rs2307166 to be more damaging than three other extensively studied SNPs. Identification of this SNP will help in determining the susceptibility of the individual to cancer, their prognosis and further treatment.


Progress and perspective on hydrogen sulfide donors and their biomedical applications.
Following the discovery of nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H2 S) has been identified as the third gasotransmitter in humans. Increasing evidence have shown that H2 S is of preventive or therapeutic effects on diverse pathological complications. As a consequence, it is of great significance to develop suitable approaches of H2 S-based therapeutics for biomedical applications. H2 S-releasing agents (H2 S donors) play important roles in exploring and understanding the physiological functions of H2 S. More importantly, accumulating studies have validated the theranostic potential of H2 S donors in extensive repertoires of in vitro and in vivo disease models. Thus, it is imperative to summarize and update the literatures in this field. In this review, first, the background of H2 S on its chemical and biological aspects is concisely introduced. Second, the studies regarding the H2 S-releasing compounds are categorized and described, and accordingly, their H2 S-donating mechanisms, biological applications, and therapeutic values are also comprehensively delineated and discussed. Necessary comparisons between related H2 S donors are presented, and the drawbacks of many typical H2 S donors are analyzed and revealed. Finally, several critical challenges encountered in the development of multifunctional H2 S donors are discussed, and the direction of their future development as well as their biomedical applications is proposed. We expect that this review will reach extensive audiences across multiple disciplines and promote the innovation of H2 S biomedicine.


Maternal-infant bonding and partner support during pregnancy and postpartum: Associations with early child social-emotional development.
The first 1000 days after conception are considered critical for healthy development and well-being throughout life. Fundamental to health practices during pregnancy and positive parenting after birth is the development of maternal-infant bonding. Previous research has demonstrated the importance of having an involved partner during pregnancy and in parenting for optimal maternal-infant bonding. The current study examined maternal-infant bonding and partner support during pregnancy and the postpartum period, and their associations with early child social-emotional development. A total of 227 women completed the Pre- and Postnatal Bonding Scale (PPBS) and Tilburg Pregnancy Distress Scale (TPDS) during pregnancy (32 weeks of gestation) and at 8 months postpartum, assessing maternal-infant bonding and partner support. Additionally, a questionnaire on social-emotional behavior of the Bayley Scales of Infant and Toddler Development was administered to mothers to measure child development at 2 years of age. Path analyses revealed an indirect positive effect of prenatal maternal-infant bonding on child social-emotional development through postnatal maternal-infant bonding, as well as mediating effects of pre- and postnatal maternal-infant bonding on the association between pre- and postnatal partner support and child social-emotional development. Our findings support the notion that an emotional connection from mother to child originates in pregnancy and that experiencing positive feelings towards the fetus promotes positive maternal-infant bonding after birth and social-emotional capacities of the child. Additionally, having a supportive partner during pregnancy and postpartum, might be essential for the development of optimal maternal-infant bonding.


An infected dentigerous cyst associated with an impacted permanent maxillary canine, inverted mesiodens and impacted supernumerary teeth.
A dentigerous cyst is an odontogenic cyst associated with the crown of the impacted or unerupted teeth. Such cyst remain initially completely asymptomatic unless when infected and can be discovered only on routine radiographic examination. Here, such a case of dentigerous cyst, which was discovered on routine radiographic examination, is discussed here.


Strategies to prevent pancreatic fistula after pancreaticoduodenectomy.
We evaluated the prevention of pancreatic fistula after pancreaticoduodenectomy in a retrospective clinical study. Eighty patients undergoing pancreaticoduodenectomy between April 2007 and August 2011 were recruited.In all patients, the pancreas was reconstructed first,followed by reconstruction of the hepatic duct and the duodenum or stomach. Pancreatic fistulae were observed in 21 of 80 patients (26.3%; Grade A/B/C: 9/12/0). The incidence of pancreatic fistula in patients with soft pancreas was higher than that inpatients with hard pancreas (p<0.01). We investigated 54 patients with soft pancreas and pancreatic fistulae were diagnosed in 19 patients (35.2%; Grade A/B/C: 8/11/0). We evaluated pancreatic drainage methods (internal stent/external stent: 20/34) and in patients with soft pancreata, pancreatic fistulae were observed in 11 patients (55%) with internal stents vs. eight patients (23.5%) with external stents(p<0.05). We evaluated the management of pancreatic drainage methods and external stents were associated with a significantly lower incidence of pancreatic fistula compared with internal stents.We expect that external drainage of soft pancreas will decrease pancreatic juice leakage into the abdominal cavity. Many randomised control trials on pancreatic drainage have been reported recently; we plan to study them.


Adrenergic receptor-mediated modulation of striatal firing patterns.
Although noradrenaline and adrenaline are some of the most important neurotransmitters in the central nervous system, the effects of noradrenergic/adrenergic modulation on the striatum have not been determined. In order to explore the effects of adrenergic receptor (AR) agonists on the striatal firing patterns, we used optogenetic methods which can induce continuous firings. We employed transgenic rats expressing channelrhodopsin-2 (ChR2) in neurons. The medium spiny neuron showed a slow rising depolarization during the 1-s long optogenetic striatal photostimulation and a residual potential with 8.6-s half-life decay after the photostimulation. As a result of the residual potential, five repetitive 1-sec long photostimulations with 20-s onset intervals cumulatively increased the number of spikes. This 'firing increment', possibly relating to the timing control function of the striatum, was used to evaluate the AR modulation. The β-AR agonist isoproterenol decreased the firing increment between the 1st and 5th stimulation cycles, while the α1-AR agonist phenylephrine enhanced the firing increment. Isoproterenol and adrenaline increased the early phase (0-0.5s of the photostimulation) firing response. This adrenergic modulation was inhibited by the β-antagonist propranolol. Conversely, phenylephrine and noradrenaline reduced the early phase response. β-ARs and α1-ARs work in opposition controlling the striatal firing initiation and the firing increment.


Comparing Cochlear Duct Lengths Between CT and MR Images Using an Otological Surgical Planning Software.
We sought to examine the intra- and interobserver variability in measuring the cochlear duct length (CDL) from magnetic resonance imaging (MRI) images versus computed tomography (CT) images using an otological surgical planning software that uses measurements of the basal turn diameter and cochlear width to estimate the CDL. Twenty-one adult cochlear implant patients with preoperative MRI and CT images. Three fellowship-trained neurotologists served as the raters in the study. One rater measured the CDL using preoperative CT scans to serve as the benchmark. Two of the raters measured the CDL on preoperative MRI scans. One rater also remeasured the scans using MRI images after a period of 1 week to assess intraobserver variability. Intraclass correlational coefficients were calculated to assess for intra- and interobserver agreement. The mean CDL measured from the CT scans was 32.7 ± 2.0 mm (range 29.4 - 37.6 mm). The mean difference between the raters when measuring the CDL using MRI scans was -0.15 ± 2.1 mm (range -3.2 to 4.3 mm). The intraclass correlational coefficients for inter-rater reliability of CDL determination using MRI scans was judged as fair to excellent (0.68; 95% CI 0.41-0.84). The intrarater reliability of CDL determination using MRI scans was judged at fair to excellent (0.73; 95% CI 0.491-0.866). We demonstrate that a validated otological surgical planning software for estimating the CDL preoperatively had comparable performance using MRI scans versus the gold-standard CT scans.


Construction, expression and assemble of EMCV VLPs and their potency evaluation.
Encephalomycarditis virus (EMCV) is an essential pathogen with a broad host range and causes enormous economic losses to the pig industry worldwide. Here, we constructed and assembled the EMCV virus-like particles (VLPs) in vitro and verified high efficiency of virus protection. Results showed that the proteins auto-assembled into VLPs successfully in vitro. The animal experiments revealed that high-titer antibody production is triggered by VLPs. Meanwhile, the mice challenged with EMCV were obviously protected. The protection rate of group VLPs with the adjuvant was 75%, while that of the VLPs group was 62.5% compared to the control. These findings indicate that recombinant EMCV VLPs have a remarkable anti-EMCV effect and could be a new vaccine candidate for the control of EMCV infection.


Chronic relapsing experimental allergic encephalomyelitis: morphological sequence of myelin degradation.
Myelin degradation in chronic relapsing experimental allergic encephalomyelitis was studied using light microscopic histochemistry and electron microscopy. In the earliest stages, a large number of myelin stripping macrophages were found. The Luxol fast blue positive degradation products were then gradually transformed into PAS positive material. No sudanophilic stage of myelin degradation was found in this model. In electron microscopy, the Luxol fast blue positive material was identified as uniformly layered lipid inclusions with a periodicity of 4.0--4.5 nm. During further digestion, this material was transformed into polymorph structured material, consisting of lamellar leaflets with a diameter of 7--10 nm, curved cylindrical profiles and granular osmiophilic material.


Development and preliminary validation of the testable assumptions questionnaire--eating disorders (TAQ-ED).
While cognitive formulations of eating disorders emphasise the role of dysfunctional assumptions regarding eating, weight and shape (EWS), less is known about the role of dysfunctional assumptions that are unrelated to EWS and those linking beliefs about EWS with negative beliefs about the self or the world. The present study aimed to develop a brief measure of dysfunctional assumptions in the eating disorders and to validate it clinically. Given that cognitive-behavioural therapy frequently involves the testing of patients' assumptions with the help of behavioural experiments, the measure was designed specifically to assess assumptions that can be addressed using such techniques. The sample consisted of 79 women with DSM-IV eating disorder diagnoses. Each participant completed the measure of testable assumptions in the eating disorders (TAQ-ED), the Eating Disorders Inventory (EDI) and the Brief Fear of Negative Evaluation scale (Brief FNE). The TAQ-ED was made up of three scales, each of which had acceptable psychometric properties. High scores on the eating attitudes/behaviours scales of the EDI and on the Brief FNE were broadly associated with dysfunctional assumptions about the world and one's body. In contrast, high scores on ego-dysfunction scales of the EDI were associated with dysfunctional assumptions about feelings. Different aspects of eating disorder pathology appear to be linked to different types of dysfunctional assumptions in the eating disorders. The clinical value of the proposed new measure of dysfunctional assumptions is discussed, and ideas are provided for behavioural experiments testing such assumptions.


The 100 Most-Cited Articles on Optic Neuritis: Trends of Subtypes, Authorship, and Time.
Optic neuritis (ON) is an optic nerve inflammation that may lead to different degrees of vision loss. In recent decades, ON research facilitated a better understanding of the disease and its subtypes. This bibliometric analysis aimed to detect the 100 most-cited medical articles related to ON in the last 50 years (1972-2021) and describe publication trends arising from the list. The Scopus database was used to locate and screen the 100 most influential ON papers based on the number of citations per article. Each entry was reviewed for the first author (name, gender, institution, and country), year of publication, journal, number of citations, ON subtype, and study design. The mean impact factor (IF) of each journal was calculated. The median number of citations was 265 (range 182-2,396). Observational studies on neuromyelitis optica-associated ON were the most common (27%), and the most influential decade was 2002-2011 (54 papers). Seventy-nine percent of articles were published in neurology journals, and a positive correlation between the mean number of citations per article and the journal mean IF was observed ( r = 0.62, P < 0.001). Between 2009 and 2021, female authors led more ON studies (52%), and more publications originated outside the USA (68%), compared with previous years. This analysis summarizes the impact and shifting trends of ON research in the last decades.


Sustained activation of mTORC1 in skeletal muscle inhibits constitutive and starvation-induced autophagy and causes a severe, late-onset myopathy.
Autophagy is a catabolic process that ensures homeostatic cell clearance and is deregulated in a growing number of myopathological conditions. Although FoxO3 was shown to promote the expression of autophagy-related genes in skeletal muscle, the mechanisms triggering autophagy are unclear. We show that TSC1-deficient mice (TSCmKO), characterized by sustained activation of mTORC1, develop a late-onset myopathy related to impaired autophagy. In young TSCmKO mice, constitutive and starvation-induced autophagy is blocked at the induction steps via mTORC1-mediated inhibition of Ulk1, despite FoxO3 activation. Rapamycin is sufficient to restore autophagy in TSCmKO mice and improves the muscle phenotype of old mutant mice. Inversely, abrogation of mTORC1 signaling by depletion of raptor induces autophagy regardless of FoxO inhibition. Thus, mTORC1 is the dominant regulator of autophagy induction in skeletal muscle and ensures a tight coordination of metabolic pathways. These findings may open interesting avenues for therapeutic strategies directed toward autophagy-related muscle diseases.


Adherence to endocrine therapy in patients with hormone receptor-positive early-stage breast cancer: a retrospective study.
The persistence and adherence to endocrine therapy (ET) in hormone receptor-positive (HR +) breast cancer patients remain far less than optimal. This retrospective study aimed to evaluate adherence to ET and to identify influencing factors in early-stage HR + breast cancer patients. A stratified random sampling method was used to select patients admitted for breast cancer surgery at a university hospital in Shanghai, China. Patients who received ET medications in the hospital information system (HIS) were included. The primary outcomes were early discontinuation of and adherence to ET. Potential factors influencing the discontinuation and adherence were assessed using univariate and multivariate logistic regression analyses. In total, 706 patients were included, and 161 (22.8%) discontinued ET in less than five years from the first prescription. The discontinuation rates from the one-year to the five-year treatment were 5.38, 16.70, 32.27, 51.52, and 50.00%, respectively (P < 0.001). The rates of adherence (defined as medication possession ratio ≥ 80%) from the first to the fifth year were 85.18, 82.25, 82.18, 72.92, and 73.68%, respectively (P = 0.18). Age, insurance, and surgery type impacted ET discontinuation and adherence. However, the type of medication only impacted the adherence to ET. Persistence and adherence to ET in patients with breast cancer remain far from optimal and decrease over time. More attention should be paid to patients aged ≥ 70 years and those without insurance who tend to have early discontinuation of ET.


[The standard operating procedure of the standardization breeding for Poecilobdella manillensis].
To prepare Standard Operating Procedure (SOP) for the artificial breeding technology of Poecilobdella manillensi. The environment of producing area and breeding technology, the control of diseases, reserving seeds for breeding, harvesting and processing,the standard of the product quality and supervision for the standardization breeding of Poecilobdella Manillensis was studied. The average yield of vital specimen of Poecilobdella Manillensis was 420.88 kg/mu, the natural hirudin in 1kg of the living specimen of Poecilobdella Manillensis contained 430,000 AT-U, and the quality index and hygienic standard of all products complied with the regulations and standards of the State. SOP is applicable for the breeding of Poecilobdella manillensi for Guangxi district.


Cannabinoid agonist, CP 55,940, facilitates intake of palatable foods when injected into the hindbrain.
Cannabinoids have been shown to influence food intake, and until recently, the neural pathways mediating these effects have remained obscure. It has been previously shown that intracerebroventricular injection of delta-9-tetrahydrocannabinol (Delta(9)-THC) causes increased consumption of palatable foods in rats, and we postulated the involvement of the hindbrain in this cannabinoid-induced food intake. Cannulated rats (both female and male groups) trained to consume sweetened condensed milk received either lateral or fourth ventricle injections of CP 55,940 and were presented with sweetened condensed milk 15 min after injection. Rats were injected over a range of doses between 100 pg and 10 microg per rat. Milk intake was recorded for a total of 3 h. Lateral ventricle injection of CP 55,940 increased milk intake at doses in the microgram range. However, CP 55,940 was effective in increasing food intake at nanogram doses when injected into the fourth ventricle. Finally, male rats appeared to be more sensitive to CP 55,940 than female rats inasmuch as milk consumption was increased at the 1 ng dose in male rats, whereas only the 10 ng dose was effective in females. These results indicate that CP 55,940 may act in the hindbrain to influence feeding behavior in rats.


Isolation and Identification of Post-Transcriptional Gene Silencing-Related Micro-RNAs by Functionalized Silicon Nanowire Field-effect Transistor.
Many transcribed RNAs are non-coding RNAs, including microRNAs (miRNAs), which bind to complementary sequences on messenger RNAs to regulate the translation efficacy. Therefore, identifying the miRNAs expressed in cells/organisms aids in understanding genetic control in cells/organisms. In this report, we determined the binding of oligonucleotides to a receptor-modified silicon nanowire field-effect transistor (SiNW-FET) by monitoring the changes in conductance of the SiNW-FET. We first modified a SiNW-FET with a DNA probe to directly and selectively detect the complementary miRNA in cell lysates. This SiNW-FET device has 7-fold higher sensitivity than reverse transcription-quantitative polymerase chain reaction in detecting the corresponding miRNA. Next, we anchored viral p19 proteins, which bind the double-strand small RNAs (ds-sRNAs), on the SiNW-FET. By perfusing the device with synthesized ds-sRNAs of different pairing statuses, the dissociation constants revealed that the nucleotides at the 3'-overhangs and pairings at the terminus are important for the interactions. After perfusing the total RNA mixture extracted from Nicotiana benthamiana across the device, this device could enrich the ds-sRNAs for sequence analysis. Finally, this bionanoelectronic SiNW-FET, which is able to isolate and identify the interacting protein-RNA, adds an additional tool in genomic technology for the future study of direct biomolecular interactions.


Karate Training Improves Skeletal Status Assessed by Quantitative Ultrasound in Girls and Premenopausal Women.
The aim of the study was to assess the influence of regular karate training on the skeletal status evaluated by quantitative ultrasound (QUS) in females. A group of 132 karate training girls and women at mean age 19.57 (standard deviation [SD] 7.64) yr (range 7.3-45.3 yr) and 322 age-, sex- and body size-matched controls were enrolled into the study. Mean training duration in the karate group was 7.52 (SD 5.05) yr and mean training frequency was 2.97 (SD 1.21) per wk. The QUS measurements were performed at hand proximal phalanges, using a DBM Sonic 1200 (IGEA, Carpi, Italy) sonographic device, which measures amplitude-dependent speed of sound (Ad-SoS [m/s]). The results of Ad-SoS obtained in karatekas were generally higher than in controls with significant difference for prepubertal girls (1966.2 [SD 46.2] vs 1942.7 [SD 38.4]; p < 0.05) and for adult women (2124.4 [SD 48.0] vs 2105.3 [SD 54.0]; p < 0.05). Regular karate training is a factor that is positively associated with results of the QUS measurements at hand phalanges in exercising females and its impact is most strongly pronounced in prepuberty and adulthood.


Predictors of involvement in the juvenile justice system among psychiatric hospitalized adolescents.
Several risk factors for juvenile justice involvement have been identified in previous research among delinquents and include mental illness, substance use, trauma and abuse, family dysfunction, poor parenting, school problems, and aggressive behavior. However, most of these predictors resulted from studies among adolescents incarcerated in the juvenile justice system. We were interested in finding out the prevalence rates of juvenile justice involvement among psychiatric inpatient adolescents and determining predictors of juvenile justice involvement in this high-risk group. Six hundred and thirty-six medical records from adolescents ages 12-17 years who were consecutively admitted to one of two psychiatric inpatient units between July 1, 2003 and June 30, 2004 were examined. Almost half (43.6%) of hospitalized adolescents had a history of juvenile justice involvement. Logistic regression analysis was conducted to determine predictors of juvenile justice involvement. Significant predictors of juvenile justice involvement included being male, parental legal history, family substance abuse history, disruptive disorder, cocaine use, being sexually active, and having a history of aggressive behavior. Adolescents in mental health or substance abuse treatment settings should be screened for juvenile justice involvement and appropriate referrals made to prevent worsening problems for at-risk youth.


Immune recognition of serum albumin.15. Localization by synthesis of antigenic site 4 of bovine serum albumin to the region around the disulfide bond 166-175.
Recently, we have localized and confirmed by synthesis the regions within which reside five major antigenic sites of bovine serum albumin and proposed that the remaining sixth major antigenic site (antigenic site 4) was localized within subdomain 3 (fragment 115-184) of albumin. In the present work, antigenic site 4 was localized to fall around the disulfide bond 166-175 by synthesis and immunochemical reactivity of the region 162-179. The synthetic 18-residue peptide was shown to bind substantial amounts of antibodies from early (38-day) and late (398-day) anti-albumin antisera from two rabbits. As much as half the total anti-albumin antibodies could be bound by the peptide from the late antisera. It was concluded that antigenic site 4 resides within, but may not include all of, the region 162-179 of albumin.


Abnormal histone replacement following BPA exposure affects spermatogenesis and fertility sequentially.
Bisphenol A (BPA) is an endocrine-disrupting chemical widely distributed in the environment. Its exposure has been linked to male infertility in animals and humans due to its ability to induce epigenetic modification. Despite extensive research confirming the impact of BPA on epigenetic regulation, fundamental concerns about how BPA causes epigenetic changes and the underlying mechanism of BPA on the male reproductive system remain unresolved. Therefore, we sought to investigate the effects of BPA on epigenetic regulation and the histone-to-protamine (PRM) transition, which is fundamental process for male fertility in testes and spermatozoa by exposing male mice to BPA for 6 weeks while giving the mice in the control group corn oil by oral gavage. Our results demonstrated that the mRNA levels of the histone family and PRMs were significantly altered by BPA exposure in testes and spermatozoa. Subsequently, core histone proteins, the PRM1/PRM2 ratio, directly linked to male fertility, and transition proteins were significantly reduced. Furthermore, we discovered that BPA significantly caused abnormal histone-to-protamine replacement during spermiogenesis by increased histone variants-related to histone-to-PRM transition. The levels of histone H3 modification in the testes and DNA methylation in spermatozoa were significantly increased. Consequently, sperm concentration/motility/hyperactivation, fertilization, and early embryonic development were adversely affected as a consequence of altered signaling proteins following BPA exposure. To our knowledge, this is the first study to indicate that BPA exposure influences the histone-to-PRM transition via altering epigenetic modification and eventually causing reduced male fertility.


Networks of polysaccharides with hydrophilic and hydrophobic characteristics in the presence of co-solute.
The present investigation deals with the changing network morphology of agarose and high methoxy pectin when mixed with polydextrose as co-solute at concentrations varying up to high level of solids. Thermomechanical analysis and micro-imaging were performed using small deformation dynamic oscillation in shear, modulated differential scanning calorimetry and environment scanning electron microscopy. Fourier transform infrared spectroscopy and wide angle X-ray diffraction were practised to examine the nature of interactions between polymer and co-solute, and the extent of amorphicity of preparations. We observed a decline in the mechanical strength of aqueous agarose preparations upon addition of high levels of polydextrose, which should be attributed to reduced enthalpic content of the coil-to-helix transition of the polysaccharide network. Glass transition phenomena were observed at subzero temperatures in condensed preparations, hence further arguing for the formation of a lightly cross-linked agarose network with changing solvent quality. High levels of co-solute induce formation of weak pectin gels at elevated temperatures (even at 95°C), which with lowering temperature exhibit increasing strength. This results in the formation of rubbery pectin gels at ambient temperature, which upon controlled cooling to subzero temperatures convert to a clear glass earlier than the agarose counterparts.


A new emerging target in cancer immunotherapy: Galectin-9 (LGALS9).
Over the past few decades, advances in immunological knowledge have led to the identification of novel immune checkpoints, reinvigorating cancer immunotherapy. Immunotherapy, represented by immune checkpoint inhibitors, has become the leader in the precision treatment of cancer, bringing a new dawn to the treatment of most cancer patients. Galectin-9 (LGALS9), a member of the galectin family, is a widely expressed protein involved in immune regulation and tumor pathogenesis, and affects the prognosis of various types of cancer. Galectin-9 regulates immune homeostasis and tumor cell survival through its interaction with its receptor Tim-3. In the review, based on a brief description of the signaling mechanisms and immunomodulatory activities of galectin-9 and Tim-3, we summarize the targeted expression patterns of galectin-9 in a variety of malignancies and the promising mechanisms of anti-galectin-9 therapy in stimulating anti-tumor immune responses.


Changes in physicochemical properties related to the texture of lotus rhizomes subjected to heat blanching and calcium immersion.
Pretreatments such as low temperature blanching and/or calcium soaking affect the cooked texture of vegetal food. In the work, lotus rhizomes (Nelumbo nucifera Gaertn.) were pretreated using the following 4 treatments, blanching at 40°C, blanching at 90°C, soaking in 0.5% CaCl2, and blanching at 40°C followed by immersion in 0.5% CaCl2. Subsequently, the cell wall material of pretreated samples was isolated and fractioned to identify changes in the degree of esterification (DE) and monosaccharide content of each section, and the texture of the lotus rhizomes in different pre-treatments was determined after thermal processing with different time. The results showed that the greatest hardness was obtained after blanching at 40°C in CaCl2, possibly attributing to the formation of a pectate calcium network, which maintains the integrity of cell walls. Furthermore, the content of galactose, rhamnose and arabinose decreased due to the breakage of sugar backbones and subsequent damage to cell walls. Our results may provide a reference for lotus rhizome processing.


Ten-Year Survivorship, Patient-Reported Outcomes, and Satisfaction of a Fixed-Bearing Unicompartmental Knee Arthroplasty.
We sought to determine the 10-year survivorship and reasons for revision for a fixed-bearing unicompartmental knee arthroplasty (UKA) design. In addition, we report on patient-reported outcomes and satisfaction and compare results of medial vs lateral compartment UKA and cemented vs cementless UKA with the same design. We performed a retrospective cohort study on a single-surgeon case series using a single fixed-bearing UKA design in 158 consecutive patients who underwent 177 UKA procedures between July 2000 and December 2010. Cases missing follow-up within the last year, clinically or via telephone, were excluded (n = 17, 10%). A cumulative incidence competing risk model was used to evaluate the cumulative incidence of failure. Cumulative incidence of revision at a mean follow-up of 10 years was 13%. The majority of revisions (43%, 10/23) were for aseptic tibial component loosening, followed by progression of osteoarthritis (5/23, 22%). All Patient Reported Outcomes Measurement Information System measures demonstrated mean T-scores within one standard deviation from the US population norm. The mean Knee Injury and Osteoarthritis Outcome Score for Joint Replacement was 96.9 (range, 40-100). The mean pain score was 3.8 (range, 0-8). Eighty-six percent of patients were satisfied with the UKA. At 10-year follow-up, the most common causes for revision were aseptic tibial loosening and adjacent compartment knee arthroplasty, and similar results were found for medial vs lateral compartment and for cemented vs cementless UKA. Surgeons should consider these findings for future UKA designs, and this represents the first study reporting on survivorship and outcomes of this specific UKA design.


Secondary Response to Chronic Respiratory Acidosis in Humans: A Prospective Study.
The magnitude of the secondary response to chronic respiratory acidosis, that is, change in plasma bicarbonate concentration ([HCO3-]) per mm Hg change in arterial carbon dioxide tension (PaCO2), remains uncertain. Retrospective observations yielded Δ[HCO3-]/ΔPaCO2 slopes of 0.35 to 0.51 mEq/l per mm Hg, but all studies have methodologic flaws. We studied prospectively 28 stable outpatients with steady-state chronic hypercapnia. Patients did not have other disorders and were not taking medications that could affect acid-base status. We obtained 2 measurements of arterial blood gases and plasma chemistries within a 10-day period. Steady-state PaCO2 ranged from 44.2 to 68.8 mm Hg. For the entire cohort, mean (± SD) steady-state plasma acid-base values were as follows: PaCO2, 52.8 ± 6.0 mm Hg; [HCO3-], 29.9 ± 3.0 mEq/l, and pH, 7.37 ± 0.02. Least-squares regression for steady-state [HCO3-] versus PaCO2 had a slope of 0.476 mEq/l per mm Hg (95% CI = 0.414-0.538, P < 0.01; r = 0.95) and that for steady-state pH versus PaCO2 had a slope of -0.0012 units per mm Hg (95% CI = -0.0021 to -0.0003, P = 0.01; r = -0.47). These data allowed estimation of the 95% prediction intervals for plasma [HCO3-] and pH at different levels of PaCO2 applicable to patients with steady-state chronic hypercapnia. In steady-state chronic hypercapnia up to 70 mm Hg, the Δ[HCO3-]/ΔPaCO2 slope equaled 0.48 mEq/l per mm Hg, sufficient to maintain systemic acidity between the mid-normal range and mild acidemia. The estimated 95% prediction intervals enable differentiation between simple chronic respiratory acidosis and hypercapnia coexisting with additional acid-base disorders.


The role of ferrichrome reductase in iron metabolism of Ustilago sphaerogena.
Ferrichrome, the ferric ionophore for Ustilago sphaerogena, can serve as a source of iron for the enzyme ferrochelatase (protoheme ferrolyase, EC 188.8.131.52) in this organism, but only after enzymatic removal of the iron from its carrier. U. sphaerogena contains a specific ferrichrome reductase (NADH:ferrichrome oxidoreductase) which catalyzes cellular dissociation of the complex by reduction of the metal to the ferrous state. A spectrophotometric assay was developed based on trapping of the ferrous ion produced by ferrozine. There is an apparent inhibition by oxygen which is thought to be due to re-oxidation of the metal under the assay conditions. The close structural analogue, ferrichrome A, is not a substrate, nor is the ester type siderochrome ferric hexahydro-N,N',N"-triacetylfusarinine C. Aluminum desferriferrichrome is inhibitory. The importance of this enzyme for the metabolism of iron in this organism is discussed.


3',5'-Di-chloro-N,N-diphenyl-[1,1'-biphen-yl]-4-amine.
The title tri-phenyl-amine derivative, C24H17Cl2N, featuring a 3,5-di-chloro-1,1'-biphenyl moiety has been synthesized and structurally characterized. The mol-ecular structure shows rotations of the phenyl rings in the range of 37-40° from the amine plane. In the crystal, the mol-ecules inter-act by van der Waals inter-actions.


The effects of live parental infant-directed singing on infants, parents, and the parent-infant dyad: A systematic review of the literature.
Singing to infants is widely accepted as an enjoyable, positive, and beneficial interaction between the parent and infant across cultures. Whilst the literature suggests that live infant-directed singing impacts the infant, the parent doing the singing and the dyad in powerful ways, no systematic review of the evidence has yet been conducted. To this end, this systematic review identified 21 studies that investigated the effect of live parental infant-directed singing. These impacts were categorized as either being directly related to the infant, the parent, or the parent-infant dyad. Three main themes - one for each of the impact categories considered - were identified using thematic analysis techniques; infant-directed singing impacts on: infants' emotional regulation, provides validation of the parent's role, and promotes affect attunement within the dyad. The findings reinforce the benefits of live parental infant-directed singing for all parties involved, particularly when parents sing to typically developing infants born at full term. In contrast, the findings were inconsistent for pre-term infants. The implications of these findings are discussed.


A System for Continuous Pre- to Post-reperfusion Intra-carotid Cold Infusion for Selective Brain Hypothermia in Rodent StrokeModels.
Intra-carotid cold infusion (ICCI) appears as a promising method for hypothermia-mediated brain protection from ischemic stroke. Recent clinical pilot studies indicate easy implementation of ICCI into endovascular acute ischemic stroke treatment. Current rodent ICCI-in-stroke models limit ICCI to the post-reperfusion phase. To establish a method for continuous ICCI over the duration of intra-ischemia to post-reperfusion in rodent stroke models, a novel system was developed. Eighteen male Sprague-Dawley rats were included. Intraluminal filament method was used for transient middle cerebral artery occlusion (MCAO). Normal saline (~ 0 °C) was delivered (≤ 2.0 mL/min) into the internal carotid artery via a customized infusion system without interruption during MCAO (intra-ischemia) to after filament withdrawal (post-reperfusion). Bilateral cortical and striatal temperatures were monitored. Hypothermia goals were a temperature reduction in the ischemic hemisphere by 2 °C prior to reperfusion and thereafter maintenance of regional brain hypothermia at ~ 32 °C limiting the administered ICCI volume to ½ of each rat's total blood volume. During ischemia, maximum brain cooling rate was achieved with ICCI at 0.5 mL/min. It took 2 min to reduce ischemic striatal temperature by 2.3 ± 0.3 °C. After reperfusion, brain cooling was continued at 2 mL/min ICCI first (over 42 s) and maintained at 32.1 ± 0.3 °C at 0.7 mL/min ICCI over a duration of 15 ± 0.8 min. ICCI (total 12.6 ± 0.6 mL) was uninterrupted over the duration of the studied phases. First system that allows continuous ICCI during the phases of intra-ischemia to post-reperfusion in small animals for selective brain cooling and for investigations of other neuroprotective infusions.


There's an "App" for That: Tips for Preparing Nurses for Roles in Mobile Health.
As health care services shift to being provided in the home and in the community, nurses must be prepared to use mobile health applications for diagnosis, monitoring, managing transitions of care, and health coaching.


Morphological changes of the tricuspid valve complex in functional tricuspid regurgitation on contrast-enhanced computed tomography.
Whether it is possible to perform morphological evaluation of functional tricuspid regurgitation (FTR) on contrast-enhanced computed tomography (CT) was examined by evaluating the relationships between the parameters measured on contrast-enhanced CT and TR severity on transthoracic echocardiography. Fifty patients underwent contrast-enhanced CT. Tricuspid annulus area (TAA), tricuspid annulus circumference (TAC), right ventricular volume (RVV), and the distances between the tips and bases of the papillary muscles were measured on contrast-enhanced CT in diastole and systole. The 50 cases were divided into 34 in the TR ≤ mild group (no TR: 3 cases, trivial TR: 24 cases, mild TR: 7 cases), and 16 in the TR ≥ moderate group (moderate TR: 8 cases, severe TR: 8 cases) using the TR grade measured by transthoracic echocardiography, and then differences between the groups were examined. Significant differences were found in TAA, TAC, and RVV (p < 0.01) and the distances between the tips of the anterior and posterior papillary muscles (p < 0.05) in both diastole and systole. Since the septal papillary muscle could not be identified in 18 cases (36.0%), only the distance between the anterior and posterior papillary muscles was measurable in all cases. On receiver-operating characteristic (ROC) curve analysis, the areas under the ROC curves (AUCs) of TAA, TAC, and RVV were all > 0.7, and the maximum AUC was 0.925 for dRVV. TAA, TAC, RVV, and the distance between the tips of the anterior and posterior papillary muscles measured on contrast-enhanced CT were shown to be significantly increased in the TR ≥ moderate group. Detailed morphological assessment of FTR is possible by contrast-enhanced CT.


Integrating memories in the human brain: hippocampal-midbrain encoding of overlapping events.
Decisions are often guided by generalizing from past experiences. Fundamental questions remain regarding the cognitive and neural mechanisms by which generalization takes place. Prior data suggest that generalization may stem from inference-based processes at the time of generalization. By contrast, generalization may emerge from mnemonic processes occurring while premise events are encoded. Here, participants engaged in a two-phase learning and generalization task, wherein they learned a series of overlapping associations and subsequently generalized what they learned to novel stimulus combinations. Functional MRI revealed that successful generalization was associated with coupled changes in learning-phase activity in the hippocampus and midbrain (ventral tegmental area/substantia nigra). These findings provide evidence for generalization based on integrative encoding, whereby overlapping past events are integrated into a linked mnemonic representation. Hippocampal-midbrain interactions support the dynamic integration of experiences, providing a powerful mechanism for building a rich associative history that extends beyond individual events.


Relation of impaired left ventricular function in mitral regurgitation to left ventricular contractile state after mitral valve replacement.
To reevaluate the postoperative contractile state and survival, 34 patients (19 men and 15 women; average age 45 years, range 23 to 65) undergoing conventional mitral valve replacement between 1980 and 1990 were studied. There were 5 cardiac deaths (2 early and 3 late). Four of 5 deaths occurred in patients who had a preoperative left ventricular end-systolic volume index > 100 ml/m2. Sixteen patients with an end-systolic volume index < 100 ml/m2 (group I), and 5 with an index > 100 ml/m2 (group II) underwent repeat catheterization 8 months (range 4 to 17) after surgery. The ratio of end-systolic wall stress to end-systolic volume index increased significantly after surgery in group I, whereas it remained reduced in group II. The postoperative end-systolic wall stress/volume index ratio correlated significantly with the preoperative end-systolic volume index (p < 0.001). In the relation between end-systolic wall stress and ejection fraction, all patients in group II had values that were less than the 95% confidence limits for the normal relation. In conclusion, patients with a preoperative end-systolic volume index > 100 ml/m2 appeared to be at high risk of incurring irreversible depressed myocardial contractility, with a high postoperative mortality.


Human propionyl CoA carboxylase: some properties of the partially purified enzyme in fibroblasts from controls and patients with propionic acidemia.
We report some properties of propionyl CoA carboxylase (PCC) partially purified from cultured human fibroblasts obtained from controls and several patients with propionic acidemia. A series of steps (Triton X-100 treatment, high speed centrifugation, ammonium sulfate precipitation, and density gradient centrifugation) led to 100- to 300-fold purification of control enzyme. Control PCC had a molecular weight of nearly 700,000, contained biotin, demonstrated a pH optinum at 8.0-8.5, was activated by potassium, and followed Michaelis-Menten kinetics for each of its substrates. It was distinguished from acetyl CoA carboxylase immunologically as well as by differential purification. Each of seven lines from patients with propionic acidemia had clearly detectable PCC activity which was less than 5% of that in control lines. Although yields were poor and purification less extensive than in control lines, mutant PCC was enriched 2- to 40-fold by the same procedures employed for the control enzyme. Mutant enzyme had a pH optimum, ionic requirements, and substrate Km's similar to those of control PCC, but was distinctly more labile to both cold and heat. These findings suggest that the markedly reduced activity of PCC in these patients results from a mutation in the PCC structural gene locus or loci which leads to the synthesis of altered enzyme protein molecules.


Effects of several dioxin-like compounds on estrogen metabolism in the malignant MCF-7 and nontumorigenic MCF-10A human mammary epithelial cell lines.
In human breast tissue, estrone (E(1)) and estradiol (E(2)) are mainly hydroxylated by cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1) to 2-hydroxyestrogens (2-OHE(1/2)) and 4-hydroxyestrogens (4-OHE(1/2)), respectively. Several studies show that 4-OHE(1/2), but not 2-OHE(1/2), may act as a carcinogen and a high estrogen 4-/2-hydroxylation ratio appears to be a marker for the presence of neoplasms. In this study, we investigated the effects of several dioxin-like compounds on estrogen 2- and 4-hydroxylation in a malignant (MCF-7) and a nontumorigenic (MCF-10A) human mammary epithelial cell line. 2- and 4-methoxyestrogen (MeOE(1/2)) formations were used as measures of the 2- and 4-hydroxylation pathways, respectively. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), and 3,3'4,4',5,5'-hexachlorobiphenyl (PCB 169) concentration dependently induced 2-MeOE(1/2) formation and ethoxyresorufin-O-deethylation (EROD) activity through induced CYP1A1 expression in MCF-7 and MCF-10A cells. 2,3',4,4',5-pentachlorobiphenyl (PCB 118) had no such effect. Effects on CYP1B1 expression and 4-MeOE(1/2) formation were less pronounced; only TCDD caused an induction, whereas PCB 169 was a potent and selective inhibitor of 4-MeOE(1/2) formation (IC(50) 0.7 and 2.2 nM PCB 169 in MCF-7 and MCF-10A cells, respectively). MCF-10A cells were less responsive toward dioxin-like compounds and the apparent EC(50) values for CYP1A1 and CYP1B1 induction in this study were 10-100 fold higher than in MCF-7 cells. The constitutive 4-/2-MeOE(1/2) ratios were 2.99 +/- 0.78 and 0.93 +/- 0.40 in MCF-7 and MCF-10A, respectively. Incubation with dioxin-like compounds resulted in a concentration-dependent decrease in the 4-/2-MeOE(1/2) ratio, but an increase in potentially carcinogenic estrogen metabolites in both MCF-7 and MCF-10A cells. This indicates that even though the 4-/2-OHE(1/2) ratio may be used as indicator for the presence of neoplasms, it is readily lowered by dioxin-like compounds and its value as a prognostic parameter for cancer risk should be further examined.


"It was just an unconditional gift." Self reflections of non-directed living kidney donors.
Non-directed living kidney donation is an important emerging type of donation, but there are concerns about ulterior motives and irrational decision-making. This study aimed to elicit the motivations and experiences of non-directed living kidney donors. Qualitative interviews were conducted with all 18 people who donated a kidney in the transplant unit of the South Island, New Zealand. Six major themes were identified: offering the chance of life (opportunity for normalcy in the recipient, good samaritanism), determination (resolute personal decision, rooted in stability, urgency, opportuneness), minimizing perceived risks (live with one kidney, trust in the medical system, physical and genetic resilience, taking chances, mental preparation, mild inconvenience), preserving anonymity (protecting donor anonymity, respecting recipient choice, receiving appreciation, knowing recipient outcomes, developing relationships), donor support (psychologic preparation, efficient coordination, reimbursement of expenses), and gaining benefits (improved fitness, empowerment and satisfaction, connectedness). Non-directed living kidney donors want to offer someone a chance of normal life; a decision driven by resoluteness and a sense of urgency. Kidney donation is perceived to offer improved fitness, and a sense of empowerment, satisfaction, and connectedness. Reluctance to consider non-directed donation programs solely on concerns of unrealistic or ill-motivations and potential feelings of donor regret appear unwarranted.


Photophysical investigations on determination of molecular structure and binding strength of supramolecular complexation between fulleropyrrolidine and a designed bisporphyrin in solution.
The present article reports, for the first time, the photophysical aspects of non-covalent interaction of a fullerene derivative, namely, C60 pyrrolidine tris-acid ethyl ester (PyC60) with a designed bisporphyrin (1) (having carbazole spacer unit) in toluene. Absorption spectrophotometric studies reveal that decrease in the absorption intensity of the Soret absorption band of 1 takes in presence of PyC60 in the solvent studied. Steady state fluorescence studies reveal efficient quenching of fluorescence intensity of 1 in presence of PyC60. Static quenching model explores a binding constant (KS) value of 2,910 dm(3) mol(-1) in toluene. Time resolved emission study establishes static quenching mechanism for the investigated supramolecule in non-polar solvent. Molecular mechanics calculations in vacuo evoke the single projection structure of the PyC60-1 complex and interpret the geometrical arrangement of both PyC60 and 1 during non-covalent complexation.


Investigation of the risk of valproic acid-induced tremor: clinical, neuroimaging, and genetic factors.
Investigation of associated risk factors of valproic acid (VPA)-induced tremor helped in increasing tolerance and optimizing treatment scheme individually. To determine the risk factors of VPA-induced tremor, with particular attention on identifying tremor-susceptible gene mutations. Epileptic patients taking VPA were divided into a tremor and a non-tremor groups. A mutation of rs9652490 in the leucine-rich repeat and immunoglobulin domain-containing Nogo-receptor-interacting protein 1 (LINGO-1) gene was determined by Sanger sequencing. Cerebellar atrophy was assessed, and various cerebellar dimensions were measured on magnetic resonance imaging (MRI) scans. One hundred and eighty-one of 200 subjects were included. Multivariate regression analysis indicated several VPA-induced tremor-related factors: females (OR = 2.718, p = 0.014), family history of tremor (OR = 7.595, p = 0.003), treatment duration (> 24 months; OR = 3.294, p = 0.002), and daily dosage (> 1,000 mg/d; OR = 19.801, p = 0.008) of VPA. Chi-square tests revealed that treatment with VPA magnesium-ER (p = 0.030) and carbamazepine combination (p = 0.040) reduced the incidence of tremor. One hundred and seventy-six gene sequencing and 86 MRI results excluded any significant difference between the two groups in the mutation of rs9652490 within LINGO-1, the ratio of cerebellar atrophy or the cerebellar-dimension values (p > 0.05). However, mutation of rs9652490 within LINGO-1 was correlated with increased cerebellar atrophy (p = 0.001), reduced cerebellar hemisphere thickness (p = 0.025), and right cerebellar hemisphere longitudinal diameter (p = 0.047). Our cohort indicated risk (female, positive family history of tremor, daily dosage > 1000 mg and treatment duration > 24 months of VPA) and protective factors (VPA magnesium-ER and combination with CBZ) of VPA-induced tremor. Mutation of rs9652490 within LINGO-1 correlated with cerebellar atrophy, neither was correlated with VPA-induced tremor.


Radiological evaluation of benign breast disorders.
The radiological features of common benign conditions of the breast and the radiological procedures used in the investigation of benign breast disorders are presented.


Signaling regulations of neuronal regenerative ability.
Different from physiological axon growth during development, a major limiting factor for successful axon regeneration is the poor intrinsic regenerative capacity in mature neurons in the adult mammalian central nervous system (CNS). Recent studies identified several molecular pathways, including PTEN/mTOR, Jak/STAT, DLK/JNK, providing important probes in investigating the mechanisms by which the regenerative ability is regulated. This review will summarize these recent findings and speculate their implications.


Autoantibodies and their Judicious Use in Pediatric Rheumatology Practice.
Autoantibody testing forms an important part of diagnostic workup of patients in Pediatric rheumatology practice. However it is important to understand that the mere presence of autoantibodies does not necessarily mean the presence of an underlying autoimmune disease. Autoantibodies may be present decades before the development of clinical manifestations of an autoimmune disease and may be viewed as harbingers of Autoimmune disease. On the other hand, low-affinity autoantibodies may be present in normal healthy individuals; these natural autoantibodies serve an important function in immune regulation and tolerance. Autoantibody testing in pediatric practice mainly includes testing for anti-nuclear antibodies, anti-dsDNA antibodies, anti-neutrophil cytoplasmic autoantibodies and antiphospholipid antibodies. Rheumatoid factor and anti-CCP do not have much significance in the diagnostic schema in pediatric rheumatology, except perhaps for classification of juvenile idiopathic arthritis (JIA) and prognostication in late-onset polyarticular JIA. The positive predictive value (PPV) of any laboratory test depends on the prevalence of the disease in the population being tested. Hence, test ordering practices greatly impact the performance characteristics and positive predictive value of any laboratory test. A restricted test ordering only in patients with clinical signs and symptoms suggestive of autoimmune disease would thus greatly increase the PPV of tests such as antinuclear antibody used for diagnosing autoimmunity.


Biometric measurement of the mouse eye using optical coherence tomography with focal plane advancement.
To demonstrate that high-resolution biometry is possible in mouse eyes in vivo, using real-time OCT with focal plane advancement by a stepper motor. OCT images of eyes were taken from nine 29-day-old C57BL/6 mice(18 eyes) on two consecutive days. A custom-built real-time OCT instrument with a stepper motor was used to advance the focal plane from the corneal apex to the retina along the ocular axis. The ocular dimensions were determined by advancement of the stepper motor as it displayed on the OCT scan images. OCT images of the entire eye, including the cornea, anterior chamber, lens, vitreous chamber, and retina, were successfully obtained from both eyes of all mice. The measured average corneal thickness from 18 eyes at the age of 29 days was 90.8+/-4.6microm, anterior chamber depth 707.4+/-21.4microm, lens thickness 1558.7+/-18.0microm, vitreous chamber depth 707.4+/-21.4microm and retinal thickness was 186.9+/-15.1microm. Total axial length (from the corneal apex to the nerve fiber layer of the retina) was 3003.3+/-44.1microm. None of them were significantly different if measured on two consecutive days, and no significant differences were found between measurements in the left and right eyes. By focal plane advancement of a real-time OCT instrument through the mouse eye, highly repeatable measurements of the ocular dimensions were obtained. This novel method may be used to study small animal models of normal and abnormal eye development.


Ulnar artery aneurysms after injury mimicking acute infection in the hand.
Two cases of ulnar artery aneurysm, with concomitant ulnar nerve compression in the palm are presented. Both followed acute injury and presented with an increasingly painful, warm swelling within 2 weeks of injury. An initial diagnosis of infection was made by experienced clinicians in each case. Ulnar artery aneurysm may be wrongly diagnosed as acute infection. It is suggested that simple excision of the aneurysm and ligation of the ulnar artery is the treatment of choice. Angiography should be reserved for those cases where there is doubt about the diagnosis or adequacy of the collateral circulation. Ulnar nerve deficit may be a result of direct injury rather than a neuropraxia from compression by the aneurysm.


Lesion Index-guided workflow for the treatment of paroxysmal atrial fibrillation is safe and effective - Final results from the LSI Workflow Study.
Pulmonary vein isolation (PVI) ablation is a standard therapy for paroxysmal atrial fibrillation (PAF). Lesion Index (LSI) is a metric to guide radiofrequency (RF) ablation using the TactiCath Ablation Catheter, Sensor Enabled with the EnSite Cardiac Mapping System (Abbott). This study (NCT-03906461) was designed to capture best practices using LSI-guided catheter ablation to treat PAF subjects in a real-world setting. This prospective single-arm observational study enrolled 143 PAF subjects in the United States, Europe, and Japan undergoing de novo PVI with RF ablation. PVI lesions were assigned to 10 anatomically defined segments. Mean LSIs achieved for all lesions were analyzed. Follow-up was conducted between 3-6 months and 12 months after the procedure. Pulmonary veins were isolated in all subjects. The mean achieved LSI was 4.9, with lower values in Europe (4.4) and Japan (4.5) than the United States (5.5). First-pass success, defined as no gaps requiring touch-up ablation after 20 minutes post isolation, was achieved in 76.2% of subjects. Use of high LSI (≥5) resulted in shorter procedure, RF, and fluoroscopy times and fewer touch-up ablations compared to low LSI (<5). At 12 months, 99.3% of subjects were free from procedure- or device-related serious adverse events and 95.7% (112/117) (35.0% on antiarrhythmic drugs) were free from recurrence and/or a repeat ablation procedure for atrial fibrillation / atrial flutter / atrial tachycardia. LSI-guided ablation strategies proved safe and effective despite differences in LSI workflows. Use of high LSI values resulted in shorter procedure, RF, and fluoroscopy times and fewer touch-up ablations compared to low LSI.


Effect of environmental exposure on charcoal density and porosity in a boreal forest.
Although charcoal's density and porosity shape its environmental roles (e.g. controlling its landscape movement and determining the internal pore space available as microbial habitat), the rate of change of these properties in the environment remains largely unknown. With time, charcoal pores may fill or charcoal particles may shatter, altering the ecosystem services delivered. In this study we examined the effects of environmental exposure on the density and porosity of charcoals pyrolyzed at two different temperatures (350 and 520°C). Fresh charcoal made from the dominant local tree (Pinus sylvestris) was returned in litter incubations to Norwegian boreal forest soils for 20months in three different placements: (i) aboveground, (ii) in the humus layer, and (iii) under the humus layer in contact with the mineral subsoil. By varying soil horizon placement we were able to separate the effects of infill from the effects of environmental disturbance on charcoal density and porosity. Environmental exposure changed charcoal density and porosity, and the response varied with environmental placement. Charcoal placed in soil layers increased in porosity by ~1-2% after 20months' incubation. This is likely because open indentations on the charcoal surface became partially occluded, creating more detectable pore space. In contrast, the porosity of charcoal incubated aboveground decreased slightly (~1-2% over 20months). Because there were no minerals or humic substances to infill the aboveground charcoal samples, this porosity reduction was likely caused by breakage of particles induced by weathering. When charcoal particles cleave through pores, internal pore space is destroyed. The small changes observed here indicate that environmental exposure did not trigger rapid shifts in charcoal density and porosity. In addition, these physical properties appear not to have reached equilibrium after 20months incubation, suggesting that the effect of environmental exposure on charcoal's physical properties occurs on the timescale of years to decades.


Correlation between centromere protein-F autoantibodies and cancer analyzed by enzyme-linked immunosorbent assay.
Centromere protein-F (CENP-F) is a large nuclear protein of 367 kDa, which is involved in multiple mitosis-related events such as proper assembly of the kinetochores, stabilization of heterochromatin, chromosome alignment and mitotic checkpoint signaling. Several studies have shown a correlation between CENP-F and cancer, e.g. the expression of CENP-F has been described to be upregulated in cancer cells. Furthermore, several studies have described a significant correlation between the expression of autoantibodies to CENP-F and cancer. Autoantibodies to CENP-F were detected in a small number of samples during routine indirect immunofluorescence (IIF) analysis for anti-nuclear antibodies (ANA) using HEp-2 cells as substrate. Using overlapping synthetic peptides covering a predicted structural maintenance of chromosomes (SMC) domain, we developed an enzyme-linked immunosorbent assay (ELISA) for detection of CENP-F antibodies. Analyzing the reactivity of the sera positive in IIF for CENP-F antibodies to overlapping CENP-F peptides, we showed that autoantibodies to several peptides correlate with the presence of antibodies to CENP-F and a diagnosis of cancer, as increased CENP-F antibody expression specific for malignant cancer patients to five peptides was found (A9, A12, A14, A16, A27). These antibodies to CENP-F in clinical samples submitted for ANA analysis were found to have a positive predictive value for cancer of 50%. Furthermore, the expression of cancer-correlated CENP-F antibodies seemed to increase as a function of time from diagnosis. These results conform to previous findings that approximately 50% of those patients clinically tested for ANA analyses who express CENP-F antibodies are diagnosed with cancer, confirming that these antibodies may function as circulating tumor markers. Thus, a peptide-based CENP-F ELISA focused on the SMC domain may aid in identifying individuals with a potential cancer.


The role of hormone therapy in urogenital health after menopause.
Menopause represents an endocrine challenge to urogenital health, as oestrogens deprivation and androgens decline significantly contributes to age-related involution of vulvovaginal tissues and lower urinary tract. Genitourinary syndrome of menopause (GSM) is a clinical entity including the chronic and progressive condition of vulvovaginal atrophy (VVA) and encompassing both anatomical and functional consequences of menopause. The term GSM describes genital, sexual and urinary symptoms with a detrimental impact on quality of life (QOL). Several treatment options are available, but many barriers are still present to adequately diagnose and treat GSM. This review aims to present current evidences about epidemiology, aetiology, diagnosis and treatment of GSM, with a focus on prescription medications [low-dose local oestrogen therapy (LET), prasterone (DHEA) and the SERM ospemifene] for urogenital symptoms in healthy postmenopausal women and in special populations, including women with premature ovarian insufficiency (POI) and breast cancer survivors (BCS).


A multiplexed bacterial two-hybrid for rapid characterization of protein-protein interactions and iterative protein design.
Protein-protein interactions (PPIs) are crucial for biological functions and have applications ranging from drug design to synthetic cell circuits. Coiled-coils have been used as a model to study the sequence determinants of specificity. However, building well-behaved sets of orthogonal pairs of coiled-coils remains challenging due to inaccurate predictions of orthogonality and difficulties in testing at scale. To address this, we develop the next-generation bacterial two-hybrid (NGB2H) method, which allows for the rapid exploration of interactions of programmed protein libraries in a quantitative and scalable way using next-generation sequencing readout. We design, build, and test large sets of orthogonal synthetic coiled-coils, assayed over 8,000 PPIs, and used the dataset to train a more accurate coiled-coil scoring algorithm (iCipa). After characterizing nearly 18,000 new PPIs, we identify to the best of our knowledge the largest set of orthogonal coiled-coils to date, with fifteen on-target interactions. Our approach provides a powerful tool for the design of orthogonal PPIs.


The cost-effectiveness of dapagliflozin in heart failure with preserved or mildly reduced ejection fraction: A European health-economic analysis of the DELIVER trial.
To determine the cost-effectiveness of dapagliflozin, added to usual care, in patients with heart failure (HF) with mildly reduced or preserved ejection fraction for the UK, German and Spanish payers using detailed patient-level data from the Dapagliflozin Evaluation to Improve the LIVEs of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial. A lifetime Markov state-transition cohort model was developed. Quartiles of the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) defined health states and monthly transition count data informed transition probabilities. Multivariable generalized estimating equations captured the incidence of HF hospitalizations and urgent HF visits, while cardiovascular deaths and all-cause mortality were estimated using adjusted parametric survival models. Health state costs were assigned to KCCQ-TSS quartiles (2021 British pound [GBP]/Euro) and patient-reported outcomes were sourced from DELIVER. Future values of costs and effects were discounted according to country-specific rates. In the UK, dapagliflozin treatment was predicted to increase quality-adjusted life years (QALYs) and life-years by 0.231 and 0.354, respectively, and extend the time spent in the best quartile of KCCQ-TSS by 4.2 months. Comparable outcomes were projected for Germany and Spain. The incremental cost-effectiveness ratios were £7761, €9540 and €5343/QALY in the UK, Germany and Spain, respectively. According to regional willingness-to-pay thresholds, 91%, 89% and 92% of simulations in the UK, Germany and Spain, respectively, were cost-effective following probabilistic sensitivity analyses. Dapagliflozin, added to usual care, is very likely cost-effective for HF with mildly reduced or preserved ejection fraction in several European countries.


[The length of DNA determines the degree of regularity of crystals of the cro-repressor complex].
The DNA-cro-repressor complex crystals have been obtained, five DNA fragments of the same nucleotide sequence and different length being used. The rotation function for crystals of complexes with hexamer (pGpT)3 . (pApC)3 and with octamer (pGpT)3 . (pApC)3 have been calculated. The order of cro-DNA complex crystals is shown to vary with DNA length, the crystal of the complex with octamer being the most perfect among all investigated complexes.


Optimal storage temperature and matrix before analyzing mycophenolic acid.
The immunosuppressant mycophenolic acid (MPA) is widely used in solid organ transplantation and increasingly in hematological conditions and autoimmune disease. Concentration monitoring is generally restricted to specialist laboratories associated with transplant centers to which samples are referred, and delays in transit may occur both from the patient to the local laboratory and from there to the specialist laboratory. The instability of the mycophenolate glucuronides in plasma is well described, but the data on MPA stability in patient samples are limited, particularly in whole blood. This study was designed to assess the stability of MPA in patient samples and to establish the correct sample type and optimal transport conditions for therapeutic drug monitoring. Whole-blood samples received in the laboratory for MPA estimation within 2 hours of phlebotomy were aliquoted, separated, and stored at a range of temperatures designed to mimic the range of transit times and conditions seen in this laboratory. Ten whole-blood samples were stored for a maximum of 4 weeks at 4°C, 21°C, or 35°C and plasma at -20°C, 4°C, 21°C, and 35°C. MPA concentrations were measured by liquid chromatography-tandem mass spectrometry. In whole blood at 35°C, there was a significant increase (P = 0.004) in median MPA concentration over time, but concentrations decreased in some samples. At 21°C and 4°C, there were more modest increases (P = 0.04 and 0.02). In plasma at 35°C, there was a significant increase from day 3 to day 28, then a decrease to day 96 in measured MPA concentration. At 21°C, there was a progressive increase in concentration from 7 to 96 days of storage (P < 0.0001). At 4°C and -20°C, plasma samples were stable for 28 days after collection, but at -20°C, there was a subsequent median increase in concentration of 15.2% at day 96. Samples should be separated as soon as practicable after collection and stored at -20°C or 4°C before transport to the analytical laboratory using subambient temperatures if possible.


Location of brain tumor intersecting white matter tracts predicts patient prognosis.
Brain tumor cells invade adjacent normal brain along white matter (WM) bundles of axons. We therefore hypothesized that the location of tumor intersecting WM tracts would be associated with differing survival. This study introduces a method, voxel-wise survival analysis (VSA), to determine the relationship between the location of brain tumor intersecting WM tracts and patient prognosis. 113 primary glioblastoma (GBM) patients were retrospectively analyzed for this study. Patient specific tumor location, defined by contrast-enhancement, was combined with diffusion tensor imaging derived tractography to determine the location of axons intersecting tumor enhancement (AXITEs). VSA was then used to determine the relationship between the AXITE location and patient survival. Tumors intersecting the right anterior thalamic radiation (ATR), right inferior fronto-occipital fasciculus (IFOF), right and left cortico-spinal tract (CST), and corpus callosum (CC) were associated with decreased overall survival. Tumors intersecting the CST, body of the CC, right ATR, posterior IFOF, and inferior longitudinal fasciculus are associated with decreased progression-free survival (PFS), while tumors intersecting the right genu of the CC and anterior IFOF are associated with increased PFS. Patients with tumors intersecting the ATR, IFOF, CST, or CC had significantly improved survival prognosis if they were additionally treated with bevacizumab. This study demonstrates the usefulness of VSA by locating AXITEs associated with poor prognosis in GBM patients. This information should be included in patient-physician conversations, therapeutic strategy, and clinical trial design.


Ultrastructural distribution of glycinergic and GABAergic neurons and axon terminals in the rat dorsal cochlear nucleus, with emphasis on granule cell areas.
A knowledge of neurotransmitters in the neurons of the rat cochlear nuclear complex is of importance in understanding the function of auditory circuits. Using post-embedding ultrastructural immunogold labelling, the distribution of glycinergic and GABAergic neurons and axonal terminals has been studied in the molecular, fusiform and polymorphic layers of the rat dorsal cochlear nucleus (DCN). This technique is not limited by the penetration of antibodies into the nervous tissue as in pre-embedding methods, and allows a fine neurochemical mapping of the nervous tissue. Numerous glycinergic and GABAergic axon terminals contain pleomorphic and flat synaptic vesicles, and are present in all layers (1, 2, 3) of the dorsal cochlear nucleus. Glycine and GABA-negative large terminals (mossy fibres) are mainly seen in granule cell areas of layer 2 (fusiform layer). Mossy fibres contact the dendrites of GABA- and glycine-negative granule cells and of the few unipolar brush cells (excitatory neurons). The least common cells in the granule cell areas are GABAergic and glycinergic Golgi-stellate neurons. In unipolar brush cells, aggregations of vesicles seem to be the origin of their characteristic ringlet-bodies. Golgi-stellate cells send their inhibitory terminals to the dendrites of granule and unipolar brush cells, occasionally directly to mossy fibres. Small or (less frequently) large GABAergic terminals contact the soma or the main dendrite of unipolar brush cells. The circuit of a hypothetical functional unit of neurons in the DCN is proposed. The inputs from auditory tonotopic or non-auditory non-tonotopic mossy fibres eventually reach pyramidal cells through axons from the granule cells or unipolar brush cells. Pyramidal cells convey an excitatory signal from the DCN to higher mesencephalic nuclei for further elaboration of the acoustic signal.


Energy content of anchovy and sardine using surrogate calorimetry methods.
European anchovy (Engraulis encrasicolus) and sardine (Sardina pilchardus) are crucial species for the marine ecosystem of the Northwestern Mediterranean Sea. They account for a high percentage of fish landings and they represent an important economic income for the fishery sector. Concerns over their stock status are rising in recent years as biomass, growth, reproductive capacity, and body condition of both species are declining, with latitudinal variations. Therefore, there is an urgent need for a body condition monitoring scheme. Energy storage variability has important implications for both fish recruitment and population structure. Direct condition indices, such as energy density (ED) with bomb calorimetry, are highly reliable for measuring the energy content, but time-consuming. Alternatively, fatmeter analysis and relative condition index (Kn) have been proposed as effective indirect methods. The aim of this study is to test the application of fatmeter as a surrogate of bomb calorimetry to infer the energy content of sardine and anchovy. To validate its use, fatmeter values were compared with both ED and Kn values. Individuals of both species were sampled monthly for a year in order to assess seasonal variations in energy content. Our results highlight that fatmeter measurements are strongly correlated with calorimetry ED for sardine, while a weaker but significant correlation was found for anchovy. The observed differences between the two species are related to their breeding strategies. Based on this study, Kn cannot be considered a good proxy of the energy density of sardine, in particular during the resting period. By contrast, fatmeter analysis appears to be a faster and suitable method to evaluate the energy content of both species routinely. In addition, we provide a linear model to infer ED from fatmeter values for both small pelagic fish. Eventually, these findings could be used to implement body condition monitoring protocols and boost continuous large-scale monitoring.


Insulin vials vs. insulin cartridges: Further cost considerations.
Many studies have provided evidence that favor the use of insulin pens over traditional insulin vials due to lower overall costs. The cost of insulin in the Royal Medical Services in Jordan is subject to other considerations due to the favorable tender prices and the process of dispensing of insulin within the Royal Medical Services. To highlight further cost considerations associated with the wastage in the use of insulin vials and cartridges in the Jordanian Royal Medical Services. Two random samples were selected from prescriptions dispensed for diabetic patients using insulin in January 2012 from the outpatient pharmacy in Al-Hussein Hospital, King Hussein Medical Center, Amman, Jordan. First sample was selected from prescriptions of patients using vials; second sample was selected from prescriptions of patients using pens and cartridges. Average costs for insulin and wastage were calculated per patient from the Royal Medical Services perspective. The average direct cost per patient using vials was JD 5.197 and for those using cartridges was JD 22.135. The average wasted quantity per patient in the first sample was more than ten times that of the second sample. The cost of the average wasted quantity per patient in the first sample (1.022 JD) was more than the double that in the second sample (0.441 JD). Although, the direct cost of insulin per patient by using vials was lower than cartridges, there was a substantial reduction in the cost of wastage by using the cartridges in the Jordanian Royal Medical Services outpatients.


How our food affects our hormones.
Food can affect the production and secretion of hormones by direct actions on the gut, by nervous reflexes, through changes in the concentration of various metabolites in the blood, or secondary to changes in circulating gut hormone levels. Not only is the composition of the diet important but also its texture, quantity and duration. GIP and insulin are used as examples of hormones whose production and secretion are diet-dependent. Their possible involvement in the pathogenesis of obesity and non-insulin-dependent (type II) diabetes is discussed.


Comparing self-reported communication skills of medical students in traditional and integrated curricula: a nationwide study.
To investigate medical students' self-assessments of their communication skills through medical school related to background factors, curriculum design and perceived medical school stress. Medical students at all year levels attending Norwegian universities in the spring of 2003 were mailed the Oslo Inventory of Self-reported Communication Skills (OSISCS) developed by the authors. Of the total number of students (N=3055), 60% responded. One school had a traditional curriculum, the other three ran integrated models. Students assessed their instrumental communication skills to increase linearly year by year, while the relational skills showed a curve-linear trajectory reaching the optimum level half-way into the curriculum. Students attending the traditional school reported lower levels of instrumental skills compared to the students from the integrated schools. In relational skills, a similar difference was maintained half-way into the curriculum, but disappeared towards the end. Perceived medical school stress correlated to the self-reported end point levels of the two types of communication skills. The trajectories of self-reported instrumental and relational skills indicate significant variations in facilitating mechanisms between curricula, cognitive processing and perceived medical school stress. Self-reported instrumental and relational communication skills develop differently in medical students over the years according to the type of curriculum. Curricula should be evaluated for improvement implementations.


Data analysis of "krokodil" samples obtained by street-like synthesis.
The data described in this work is related to be the subject of an article in the Forensic Science International, titled: "The harmful chemistry behind "krokodil": street-like synthesis and product analysis" (http://dx.doi.org/10.1016/j.forsciint.2015.07.042) [1]. The data presented here provides additional description of the chemical profile of "krokodil". Physicochemical and organoleptic characteristics, TLC profile, UV/Vis, (1)H NMR and FTIR spectrum are presented. These data validate the proposed synthetic procedure and pathway and give further information about the contaminants present in "krokodil".


Computed tomography in neurocysticercosis: a 10-year long evolution analysis of 100 patients with an appraisal of a new classification.
Three hundred and fifty seven computed tomography (CT) from 100 different patients with neurocysticercosis (NC) were studied between 1979 and 1988. All patients were treated with praziquantel (PZQ). A new classification attempting to recognize the CT evolution profile in NC as well as assigning a possible link between CT findings and biological conditions of cysts is evaluated. It was possible to conclude that: intact cysts remain unchanged in consecutive CTs by 11 months and exhibit signs of degeneration in about 18 months after PZQ drug therapy; degenerating cysts can be detected by 10.5 months, disappear in 11 months and become nodular calcifications in about 25 months. Therefore, a time period of at least 36 months can be estimated for the complete evolution profile of cysts in the brain parenchyma.


5alpha-reductase activity of genital and nongenital skin fibroblasts from patients with 5alpha-reductase deficiency, androgen insensitivity, or unknown forms of male pseudohermaphroditism.
Serially subcultured fibroblast strains from genital (foreskin, labium majus) skin, as a group, have considerably more steroid (testosterone) 5alpha-reductase activity than those form nongenital skin. Foreskin strains varied 40-fold and labial strains even more. Labial strains overlapped nongenital strains of either sex more frequently than did prepuce strains. The activity of foreskin strains from two siblings with proven 5alpha-reductase deficiency was clearly lower than that of any of 18 control stains. The comparative behavior of the various strain types indicates that labial and nongenital strains should not be used to support a clinical suspicion of male pseudohermaphroditism due to 5alpha-reductase deficiency. The activities of labial strains from patients with complete androgen insensitivity (testicular feminization) - five with the receptor-negative variety and two with the receptor-positive type - were as variable as those of control labial strains. The decreased 5alpha-reductase activity observed in fresh skin slices of some patients is probably and expression of their functional estrogen/androgen imbalance in vivo.


Important properties of anion exchange resins for efficient removal of PFOS and PFOA from groundwater.
Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) present in various water sources have raised a serious concern on their health risk worldwide. Anion exchange is known to be one of the effective treatment methods but the resin properties suitable for theses contaminants have not been fully understood. We examined four commercially available anion exchange resins with different properties (DIAION™ PA312, HPA25M, UBA120, and WA30) and one polymer-based adsorbent (HP20), for their PFOA and PFOS removal in the batch experiment. All or a part of the selected resins were further characterized for their functional group, surface morphology and pore size distribution. The 72 h batch experiment with the 100 mg/L PFOA or PFOS in the laboratory pure water matrix showed a superior capacity of the strong base anion exchange resins, the porous-type HPA25M and PA312, and the gel-type UBA120, for PFOA removal (92.6-97.9%). Among those resins, the high porous HPA25M was suggested most effective due to its remarkably high reaction rate and effectiveness to PFOS (99.9%). In the groundwater matrix, however, the performance of the those anion exchange resins was generally suppressed, causing up to 71% decrease in their removal rates. The least matrix impact was observed for PFOS removal by HPA25M, which indicated the resin's high selectivity to the contaminant. The physiochemical analysis indicated that the presence of relatively large pores (1 nm-10 nm) over HPA25M played an important role in the PFAS removal.


Evaluating patients with acute ischemic stroke with special reference to newly developed atrial fibrillation in cerebral embolism.
Cardioembolic strokes are extensive and have a poor prognosis. To identify the cardiovascular risk factors of cardioembolic stroke, we evaluated the cardiovascular status with special reference to persistent atrial fibrillation (AF) and paroxysmal atrial fibrillation (PAF) combined with the type of acute ischemic stroke. We divided 315 consecutive patients admitted to our Department of Neurosurgery with an acute ischemic stroke into four types of brain infarction using clinical history, onset pattern of stroke, and brain imaging: cardioembolic (group E, n = 105), lacunar (group L, n = 92), atherothrombotic (group T, n = 111), and unclassified (n = 7). All patients underwent standard electrocardiography (ECG), a 24-hour ECG recording (Holter ECG) and transthoracic echocardiography (UCG). Persistent AF or PAF was detected in 97 patients (31.5%) using Holter ECG: more frequently in group E (67.6%) than in groups L (15.2%) or T (9.2%). Persistent AF or PAF was first diagnosed on admission using a standard ECG in 16 patients (5.2%) with no previous history and 14 of these patients belonged to group E (13.3%). PAF was newly detected on Holter ECG in another 26 patients (8.4%) and 13 of these patients (12.4%) belonged to group E. Concerning UCG, left atrial enlargement and mitral regurgitation were more frequent in group E than in group L or T. Holter ECG in addition to ECG on admission is important for detecting persistent AF or PAF in patients with ischemic stroke, especially with cardioembolism as diagnosed by neuroimaging.


Nonlinear time course of brain volume loss in cognitively normal and impaired elders.
The goal was to elucidate the time course of regional brain atrophy rates relative to age in cognitively normal (CN) aging, mild cognitively impairment (MCI), and Alzheimer's disease (AD), without a priori models for atrophy progression. Regional brain volumes from 147 cognitively normal subjects, 164 stable MCI, 93 MCI-to-AD converters and 111 ad patients, between 51 and 91 years old and who had repeated 1.5 T magnetic resonance imaging (MRI) scans over 30 months, were analyzed. Relations between regional brain volume change and age were determined using generalized additive models, an established nonparametric concept for approximating nonlinear relations. Brain atrophy rates varied nonlinearly with age, predominantly in regions of the temporal lobe. Moreover, the atrophy rates of some regions leveled off with increasing age in control and stable MCI subjects whereas those rates progressed further in MCI-to-AD converters and AD patients. The approach has potential uses for early detection of AD and differentiation between stable and progressing MCI.


Antitumor effects and blood flow dynamics after photodynamic therapy using benzoporphyrin derivative monoacid ring A in KLN205 and LM8 mouse tumor models.
Photodynamic therapy (PDT) using benzoporphyrin derivative monoacid ring A (BPD-MA) induces direct tumor cell damage and microvascular injury. We administered BPD-MA at 3h or 15min before laser irradiation to KLN205 and LM8 tumors in murine models. Tumor growth delay was induced more effectively by 15-min-interval PDT than by 3-h-interval PDT. Vascularity and blood perfusion was significantly decreased by 15-min-interval PDT. We observed death of all tumor cells, except peripheral cells, in the 3-h-interval PDT group, and death of cells around the damaged tumor vasculature in the 15-min-interval PDT group. Thus, 15-min-interval PDT enhanced the antitumor effect by damaging tumor vasculature.