Joint outpatient clinics for the adult with congenital heart disease at the district general hospital: an alternative model of care.
Congenital heart disease (CHD) affects approximately 250,000 adults in the UK. Most of these patients would benefit from specialized follow-up. However, there is at present a significant shortfall of specialized tertiary care expertise and facilities for this growing cardiovascular field in the UK and around the world. We aimed to report our experience with a joint adult CHD clinic run in a district general hospital with regular input from the local cardiology team and a visiting adult CHD specialist. In total, 148 patients aged 33.6+/-14.1 years were seen once or more in 12 clinics over the study period (September 1999 to January 2003). Diagnostic case mix consisted of 2.9% complex, 67.9% moderate and 29.2% minor cases of CHD. Twenty percent of patients visited the counterpart tertiary center for additional investigations (mostly MRI) and 8% for intervention (with no operative mortality). There was one death during the study period giving an overall mortality of 0.2%/year. Patients were referred to the clinic from tertiary centres, the local cardiology and paediatric clinics and with time from obstetric and community sources. Nonattendance rates were relatively low, comparing favourably with tertiary care. This model of joint care for the adult CHD patient at a general district hospital with regular onsite specialized input appears to be effective and highlights the need for additional resource allocation to provide optimal care for these patients. Our data may be useful in future planning for CHD services.


Network-based analysis for identification of candidate genes for colorectal cancer progression.
Although high-throughput biological technologies have been producing a vast amount of multi-omics data regarding cancer genomics and several disease susceptible genes have been reported, many of these genes are likely to be irrelevant for the cancer process because only one feature of the tumor pathway could be focused on. By identifying 'CpG core', which was extracted from CpG sites in genomic DNA by our newly developed method, we performed integrated analysis using gene expression and DNA methylation profiles of 116 colorectal cancer samples. First, based on gene expression values, colorectal cancer samples were divided into three clusters (Cluster-1, -2, and -3) by k-means clustering. The 5-year overall survival rates of colorectal cancer patients were 74.8%, 29.2%, and 29.4% in Cluster-1, -2, and -3, respectively, and the prognosis of Cluster-2 was significantly poorer than that of the other two clusters owing to liver metastasis (P < 0.001). Second, each cluster was divided into two subgroups based on methylation status, and the 5-year overall survival rate of Cluster-1H (36.8%) was significantly shorter than that of Cluster-1L (96.1%) due to the accumulation of aberrant DNA methylation (P = 0.014). Third, network-based analysis using expression and methylation profiles demonstrated that nucleoporin family genes were downregulated in Cluster-2 and that the PTX3 gene was highly methylated in Cluster-1H. These combined data indicate that integrated analysis can identify disease characteristics that would be missed using single comprehensive analysis, and that multiple pathways would play pivotal roles in the liver metastasis of colorectal cancer.


OTUB1's role in promoting OSCC development by stabilizing RACK1 involves cell proliferation, migration, invasion, and tumor-associated macrophage M1 polarization.
Ovarian tumor domain, ubiquitin aldehyde binding 1 (OTUB1), a deubiquitinating enzyme known to regulate the stability of downstream proteins, has been reported to regulate various cancers tumorigenesis, yet its direct effects on oral squamous cell carcinoma (OSCC) progression are unclear. Bioinformatics analysis was performed to screen for genes of interest, and in vitro and in vivo studies were carried out to investigate the function and mechanism of OTUB1 in OSCC. We found that OTUB1 was abnormally elevated in OSCC tissues and positively associated with the pathological stage and tumor stage. Knockdown of OTUB1 impaired the malignance of OSCC cells - suppressed cell proliferation, invasion, migration, and xenografted tumor growth. OTUB1 silencing also drove tumor-associated macrophage M1 polarization but suppressed M2 polarization, and the induction of M1 polarization inhibited the survival of OSCC cells. However, OTUB1 overexpression exerted the opposite effects. Furthermore, the protein network that interacted with the OTUB1 protein was constructed based on the GeneMANIA website. Receptor for activated C kinase 1 (RACK1), a facilitator of OSCC progression, was identified as a potential target of the OTUB1 protein. We revealed that OTUB1 positively regulated RACK1 expression and inhibited RACK1 ubiquitination. Additionally, RACK1 upregulation reversed the effects of OTUB1 knockdown on OSCC progression. Overall, we demonstrated that OTUB1 might regulate OSCC progression by maintaining the stability of the RACK1 protein. These findings highlight the potential roles of the OTUB1/RACK1 axis as a potential therapeutic target in OSCC.


Use of photodynamic therapy in the treatment of vocal cord carcinoma.
The photodynamic therapy of superficial vocal cord carcinoma is a promising new technique. Patients were irradiated with 630 nm light from an Aurora dye laser under general anaesthesia 72 h after a haematoporphyrin derivative (HpD) injection. So far, 32 patients have been treated for small epidermoid carcinoma of the glottis without anterior commissure. There have been no undesired effects due to the photosensitizer or the dye laser. The results show seven failures and 25 positive responses, of which three patients were treated more than 4 years ago.


Synaptic actions of individual vestibular neurones on cat neck motoneurones.
1. Unitary synaptic potentials evoked by the activity of single vestibulocollic neurones were recorded by means of spike-triggered signal averaging in neck extensor motoneurones of decerebrate cats. Properties of the vestibulocollic neurones which produced the potentials were examined.2. Vestibulocollic neurones were first identified as projecting to the C3 grey matter by antidromic microstimulation within the C3 extensor motoneurone pool. The spontaneous or glutamate-driven activity of the vestibulocollic neurones was then used to trigger the averaging computer. In this way ten inhibitory and two excitatory neurones were identified (20% of neurones tested).3. Action potentials in local branches of vestibulocollic neurones were usually recorded in the vicinity of motoneurones. Mean orthodromic conduction time from the foot of the extracellular spike, recorded in the vestibular nuclei, that triggered the averager was 0.72 msec. Mean synaptic delay was 0.4 msec.4. I.p.s.p.s had a mean time to peak of 0.81 msec and were readily reversed by injection of hyperpolarizing current. These data, together with the shape indices of i.p.s.p.s indicate that they are generated proximally on motoneurones.5. All vestibulocollic neurones making synapses with motoneurones were monosynaptically driven by stimulation of the ipsilateral vestibular nerve. Four out of seven tested were inhibited by stimulation of the contralateral vestibular nerve (commissural inhibition).6. Two excitatory neurones were located in Deiters' nucleus or on the Deiters'-descending border. Inhibitory neurones were found relatively medially in the vestibular complex in the medial, descending and Deiters' nuclei.7. Vestibulocollic neurones acting on motoneurones were tested for axon branching to more caudal levels of the spinal cord with electrodes placed at C5-7. Both of the excitatory and two out of nine inhibitory neurones branched.


Two modes of microtubule-associated protein 1B phosphorylation are differentially regulated during peripheral nerve regeneration.
Two major modes of MAP1B phosphorylation (I and II), respectively recognized by monoclonal antibodies 150 and 125, have been related to remodeling and formation of processes in the mature nervous system. To gain insight into the cytoskeletal modifications underlying peripheral nerve regeneration, the pattern of expression of both MAP1B phosphorylated modes was studied during this process. Sciatic nerves from adult Wistar rats were crushed and animals allowed to survive for 5, 7, 10 or 14 days. After those survival periods, damaged and undamaged sciatic nerves, dorsal root ganglia (DRG), and spinal cords, were subjected to immunohistochemistry and Western blot, using antibodies 150 and 125. At all survival periods analysed, MAP1B phosphorylated at mode I was concentrated at the distal region of regenerating nerves whereas mode II phosphorylation underwent an overall decrease in regenerating axons that was less evident in more proximal nerve regions. Very high levels of MAP1B phosphorylated at mode II were detected in the bodies of DRG neurons and in bodies and dendrites of spinal motor neurons. This phosphorylation mode was also encountered in some Schwann cells and oligodendroglia associated with more proximal regions of regenerating axons. In this study we conclude that MAP1B was differentially phosphorylated depending on the cell type, subcellular compartment and stage of the regenerative process and discuss the possible functional implications that differential expression of each MAP1B phosphorylation mode might have during nerve regeneration.


An exercise program to improve fall-related outcomes in elderly nursing home residents.
This study tested a 3-month ankle-strengthening and walking program designed to improve or maintain the fall-related outcomes of balance, ankle strength, walking speed, risk of falling, fear of falling, and confidence to perform daily activities without falling (falls efficacy) in elderly nursing home residents. Nursing home residents (N = 81) between the ages of 64 and 100 years participated in the study. Two of the fall-related outcomes, balance and fear of falling, were maintained or improved for the exercise group in comparison to the control group.


Myringitis bullosa haemorrhagica associated with meningo-encephalitis.
An unusual case of a patient presenting with myringitis bullosa haemorrhagica (MBH), who subsequently developed acute otitis media and meningo-encephalitis, is described. The aetiology of MBH is discussed, and recommendations for the management of patients with acute otitis are made.


Nonsteroidal anti-inflammatory drug-associated toxicity of the liver, lower gastrointestinal tract, and esophagus.
Although upper gastrointestinal (GI) adverse events are the most common consequences of nonsteroidal anti-inflammatory drug (NSAID) use, there are other GI side effects that can contribute to the morbidity and mortality associated with these drugs. NSAID-associated toxicity of the large and small bowel is increasingly recognized in clinical practice, as enteroscopic procedures become more frequently used. This lower GI toxicity may have several different manifestations: ulcerations, strictures, colitis, or exacerbation of inflammatory bowel disease. Hepatic injury, most likely due to an idiosyncratic reaction resulting from an immunologic response or altered metabolic pathways, is another sequela of NSAID use that is usually reversible. Although hepatotoxicity is listed as a class warning for NSAIDs, aspirin, diclofenac, and sulindac are most commonly associated with this problem. Surveillance for hepatic injury is not always reliable, and the low frequency of both hepatic and lower GI toxicity in NSAID users renders these events difficult to characterize. An increase in awareness, surveillance, and reporting of these events can lead to a better understanding of the risk factors and etiology associated with NSAID toxicity.


Replication: DNA building block synthesis on demand.
Correct regulation of DNA nucleotide biosynthesis is emerging as a key issue of importance for genome integrity. The fission yeast Spd1 protein can modulate the activity of ribonucleotide reductase (RNR) by at least three different mechanisms. Now a paper reports that Spd1 turnover is linked to ongoing DNA synthesis.


A novel transverse expression domain in the mouse cerebellum revealed by a neurofilament-associated antigen.
The mammalian cerebellum is composed of a highly reproducible array of transverse zones, each of which is subdivided into parasagittal stripes. By using a combination of Purkinje cell antigenic markers and afferent tracing, four transverse zones have been identified: the anterior zone (AZ: approximately lobules I-V), the central zone (CZ: approximately lobules VI-VII), the posterior zone (PZ: approximately lobules VIII-dorsal IX) and the nodular zone (NZ: approximately ventral lobule IX+lobule X). Neurofilament-associated antigen (NAA) is an epitope recognized by a monoclonal antibody, which is expressed strongly in association with neurofilaments. During perinatal cerebellar development, anti-NAA immunocytochemistry reveals novel features of cerebellar organization. In particular, the CZ is reproducibly subdivided into anterior and posterior components. Between embryonic day 17 and postnatal day 7 NAA immunoreactivity is expressed selectively by a parallel fiber bundle that is restricted to lobule VII, thereby distinguishing the CZ anterior (lobules VIa, b) from the CZ posterior (lobule VII). The novel restriction boundary at lobule VII/VIII, which is also reflected in the morphology of the external granular layer and aligns with a gap in the developing Purkinje cell layer, precedes the morphological appearance of the posterior superior fissure between lobules VIb and VII. In addition, afferent axons to the CZ terminate in an array of parasagittal stripes that is probably a specific climbing fiber projection. Thus, the transverse zone architecture of the mouse cerebellum is more complex than had previously been appreciated.


Correction to: Authors' Reply: Routine Pathology and Postoperative Follow-Up are not Cost-Effective in Cholecystectomy for Benign Gallbladder Disease.
In the original article, Madelon J. H. Metman's given name is incorrect. It is correct as reflected here.


Biogerontology in the Czech Republic.
Authors provide results of their review of research in the field of biogerontology. Despite the fact that the term "biogerontology" is not commonly used in Czech scientific practice, there have been many research efforts in this field. Up to present, the Czech research teams have focused on the theoretical and biological models of ageing, its immunological aspects, the risk factors of unsuccessfull human ageing, and also metabolic and nutritional factors. Many research teams are dealing with the mechanisms of the neurodegeneration. The authors conclude that better coordination and systematic funding of research in gerontology is needed because of the actual demographic challenges.


From waking to sleeping: neuronal and chemical substrates.
Multiple arousal systems maintain waking through the actions of chemical neurotransmitters that are released from broadly distributed nerve terminals when the neurons fire. Among these, noradrenaline-, histamine- and orexin-containing neurons fire during waking with behavioral arousal, decrease firing during slow-wave sleep (SWS) and cease firing during paradoxical sleep (PS), which is also known as rapid-eye-movement sleep. By contrast, acetylcholine (ACh)-containing neurons discharge during waking, decrease firing during SWS and fire at high rates during PS in association with fast cortical activity. Neurons that do not contain ACh, including GABA-containing neurons in the basal forebrain and preoptic area, are active in a reciprocal manner to the neurons of the arousal systems: one group discharges with slow cortical activity during SWS, and another discharges with behavioral quiescence and loss of postural muscle tone during SWS and PS. The reciprocal activities and interactions of these wake-active and sleep-active cell groups determine the alternation between waking and sleeping. Selective enhancement and attenuation of their discharge, transmitter release and postsynaptic actions comprise the substrates for the major stimulant and hypnotic drugs.


Stem cells and Parkinson's disease: toward a treatment, not a cure.
Early clinical trials designed to treat Parkinson's disease by transplantation of fetal tissue containing dopamine neuron precursors yielded promising results, but the approach retains several limitations. Multiple recent papers describe longer-term outcomes in these patients, and two additional studies offer novel approaches that may lead to autologous sources of transplantable dopamine neurons.


Primary Care Physicians' Perspectives in Leading Breast Cancer Follow-Up Care.
Limited data exist on the barriers associated with transitioning breast cancer follow-up care to primary care physicians (PCPs). This study aimed to describe the current perspectives of PCPs in managing breast cancer follow-up. An online survey was distributed to PCPs in Toronto, ON, Canada. Questions examined PCPs' view of transitioning breast cancer follow-up care to their practices. Of 800 PCPs invited, 126 responded (response rate: 15.7%). The types of practice models amongst respondents included blended capitation (42.9%), blended salary (27%), and fee-for-service (17.5%). Seventy-seven percent of respondents stated they provided follow-up care. Approximately half of the respondents stated they were somewhat comfortable providing follow-up care. PCP-led follow-up care was considered either very (49.2%) or somewhat appropriate (30.2%). When asked about financial remuneration, 43.7% of respondents stated it was somewhat important. The factors that influenced the feasibility of PCP-led follow-up care included receipt of a detailed follow-up care plan provided by the specialist after discharge (81%), the ability to re-refer to specialists rapidly (56.3%), and the ability to obtain regular updates of best practice changes (59.5%). The preferred means of educational updates included E-mail (40.5%), continuing medical education events (30.2%), and electronic medical records (19.8%). When the fee model was taken into consideration there was no significant difference in opinions regarding follow-up care. Transitioning to a PCP-led model was supported by most of the PCPs who participated in this study. Their perspective on PCP-led follow up care and barriers associated with implementation of this model of care needs to be further explored with future studies that include larger sample size and a more diverse PCP population.


Review of various techniques of small bowel transplantation in pigs.
Because of anatomical and physiological similarities to humans, porcine small bowel transplantation (SBTx) can be used as an appropriate experimental model in the field of surgical research. Various approaches to SBTx have been described in literature. The aim of this work is to present a review of different surgical techniques of SBTx which have been developed using the porcine model. Our analysis of Medline-cited studies dealing with different techniques of SBTx in porcine models was particularly focused on surgical aspects. With regard to graft procurement and enterectomy, the reported techniques vary widely. Arterial reconstruction is mainly conducted by performing the anastomosis between the superior mesenteric artery (SMA) of the donor and SMA or infrarenal aorta of the recipient. Alternatively, an aortic segment of the donor can be anastomosed to the infrarenal aorta of the recipient. Venous anastomosis is frequently performed between the superior mesenteric vein (SMV) of the donor and SMV or the inferior vena cava (IVC) of the recipient. Some studies also report venous anastomosis between the portal vein of the donor and the recipient. Bowel continuity is then restored by end-to-end or end-to-side anastomosis. Remarkable results were generated thanks to improved techniques which include proximal side-to-side ileo-ileal anastomosis with double-barrel ileostomy, or so-called "Paul-Mikulicz-Ileostomy". Most frequently used were jejunostomy and the "Bishop-Koop-Ileostomy"--where the proximal part of the bowel is anastomosed end-to-side to the distal part, which is then exteriorized as an ostomy. Based on the techniques presented in this review, one must select the most suitable surgical technique of porcine SBTx among those various models.


Toxoplasma gondii, Dirofilaria immitis, feline immunodeficiency virus (FIV), and feline leukemia virus (FeLV) infections in stray and pet cats (Felis catus) in northwest China: co-infections and risk factors.
This study was conducted to estimate the prevalence of Toxoplasma gondii, Dirofilaria immitis, feline immunodeficiency virus (FIV), and feline leukemia virus (FeLV) infections among stray and pet cats in Lanzhou, northwest China, and to identify the influence of age, gender, and regions on seropositivity. T. gondii antibodies were examined in cat sera by the modified agglutination test (MAT). The circulating antigens of D. immitis and FeLV and specific antibodies to FIV were examined using kits commercially available. The overall prevalence of T. gondii, FIV, FeLV, and D. immitis was 19.34, 9.12, 11.33, and 3.04 %, respectively. For the genetic characterization of T. gondii genotypes in cats, genomic DNA was extracted from the seropositive cats and the T. gondii B1 gene was amplified using a semi-nested PCR. DNA samples giving positive B1 amplification were then genotyped using multilocus PCR-RFLP. Two T. gondii genotypes (ToxoDB#9 and ToxoDB#1) were identified. Results of the multivariate logistic regression analysis showed that older cats are more likely to be seropositive than juveniles for T. gondii, FIV, FeLV, and D. immitis. This is the first report of T. gondii genotypes in cats in northwest China. Moreover, the present study is the first study of retrovirus and D. immitis seroprevalence in cats in China. The results revealed that T. gondii, FIV, and FeLV infections are common in stray and pet cats in northwest China.


Geomicrobiology in oceanography: microbe-mineral interactions at and below the seafloor.
Oceanography is inherently interdisciplinary and, since its inception, has included the study of microbe-mineral interactions. From early studies of manganese nodules, to the discovery of hydrothermal vents, it has been recognized that microorganisms are involved at various levels in the transformation of rocks and minerals at and below the seafloor. Recent studies include mineral weathering at low temperatures and microbe-mineral interactions in the subseafloor "deep biosphere". A common characteristic of seafloor and subseafloor geomicrobiological processes that distinguishes them from terrestrial or near-surface processes is that they occur in the dark, one or more steps removed from the sunlight that fuels the near-surface biosphere on Earth. This review focuses on geomicrobiological studies and energy flow in dark, deep-ocean and subseafloor rock habitats.


Criteria for improving visual acuity in ischaemic branch retinal vein occlusion using argon laser.
To re-assess the value of argon laser treatment for macular oedema in ischaemic branch retinal vein occlusion (I-BRVO). Case series consisting of three patients with macular oedema following I-BRVO. Three patients were studied including two patients where ischaemia extended to include the foveal avascular zone (FAZ), with additional retinal neovascularisation in one of these. Heavy, overlapping areas of treatment were applied to the ischaemic retina up to 500 microns from the fovea. All cases in the series benefited from significantly improved visual acuity. In one case laser was given several years after the initial retinal vasculopathy. Argon laser treatment may improve visual acuity in I-BRVO even with severe ischaemia extending into the FAZ. Treatment intensity must be sufficient to destroy ischaemic retina. Visual benefit may last for several years, and treatment can be undertaken several years after I-BRVO. The benefit to visual acuity of argon laser treatment in I-BRVO needs to be re-assessed in a prospective study.


FLT3 receptors with internal tandem duplications promote cell viability and proliferation by signaling through Foxo proteins.
In about 30% of the patients with acute myeloid leukemia, activating FLT3 receptor mutations have been identified, often as in-frame internal tandem duplications (ITD) at the juxtamembrane domain of the receptor. FLT3-ITD receptors exhibit constitutive tyrosine kinase activity in the absence of FLT3 ligand (FL) binding, and when expressed in cytokine-dependent cell lines and primary hematopoietic cells suppress programmed cell death and increase cell division. However, the signaling pathways important for transformation, in particular the nuclear targets, are unknown. Here we demonstrate that FLT3-ITD expression in Ba/F3 cells results in activation of Akt and concomitant phosphorylation of the Forkhead family member Foxo3a. Phosphorylation of Foxo proteins through FLT3-ITD signaling promotes their translocation from the nucleus into the cytoplasm, which requires the presence of conserved Akt phosphorylation sites in Forkhead transcription factors and PI3K activity. Induction of Foxo3a phosphorylation by FLT3-ITD receptors in Ba/F3 cells correlates with the suppression of Foxo-target genes p27Kip1 and the proapoptotic Bcl-2 family member Bim. Specifically, FLT3-ITD expression prevents Foxo3a-mediated apoptosis and upregulation of p27Kip1 and Bim gene expression. These data indicate that the oncogenic tyrosine kinase FLT3 can negatively regulate Foxo transcription factors, thereby promoting cell survival and proliferation.


Immunochemical comparison of lipoamide dehydrogenases from various sources and reactivity of various lipoamide dehydrogenases with rat heart pyruvate dehydrogenase-subcomplex.
Lipoamide dehydrogenases from various sources were purified and their immunochemical properties were compared. Antibody against rat lipoamide dehydrogenase reacted with rat, human, pig, pigeon and frog enzymes, but not with enzymes from E. coli, yeast and Ascaris. Anti-Ascaris enzyme and anti-E. coli enzyme antibodies reacted with Ascaris and E. coli enzymes, respectively. The pyruvate dehydrogenase subcomplex, which consists of pyruvate dehydrogenase and lipoate acetyltransferase, was prepared by releasing the lipoamide dehydrogenase from rat heart pyruvate dehydrogenase complex by anti-lipoamide dehydrogenase antibody. Lipoamide dehydrogenases from various sources were added to rat pyruvate dehydrogenase subcomplex and the complex overall activity was measured. Each lipoamide dehydrogenase effectively recovered the overall activity of rat pyruvate dehydrogenase subcomplex to 80% of the original activity.


Patterns of atypical muscle tone in the general infant population - Prevalence and associations with perinatal risk and neurodevelopmental status.
Muscle tone is an indispensable element in motor development. Its assessment forms an integral part of the infant neurological examination. Knowledge on the prevalence of atypical tone in infancy is lacking. To assess the prevalence of atypical muscle tone in infancy and of the most common atypical muscle tone patterns, and associations between atypical tone and perinatal risk and neurodevelopmental status. Cross-sectional study. 1100 infants (585 boys; gestational age 39.4 weeks (27.3-42.4)), 6 weeks-12 months corrected age, representative of the Dutch population. Muscle tone and neurodevelopmental status were assessed with the Standardized Infant NeuroDevelopmental Assessment (SINDA). Perinatal information was obtained by questionnaire and medical records. Univariable and multivariable statistics were applied. Ninety-two infants (8%) had atypical muscle tone in 3-4 body parts (impaired pattern), while atypical muscle tone in 1-2 body parts was observed in 50%. Isolated leg hypotonia and isolated arm hypertonia were most common. Isolated arm hypertonia and the impaired pattern were most clearly but only moderately associated with perinatal risk. These patterns were also most clearly associated with lower neurological scores. Only the impaired pattern was associated with lower developmental scores. Atypical muscle tone in one or two body parts is common in infancy and has in general little clinical significance. This finding corresponds to the well-known high prevalence of a typical but non-optimal neurological condition. Eight percent of infants show atypical muscle tone in 3-4 body parts. This clinically relevant pattern is associated with perinatal risk and less favourable neurodevelopmental status.


Traumatic asphyxia: an unusual cause of traumatic coma and paraplegia. Case report.
An unusual case of traumatic asphyxia with cerebral and spinal cord symptoms is presented. A survey of the literature indicates that a primary cord lesion is very rare as a consequence of such a trauma. The possible pathogenetic mechanisms of these neurological manifestations are discussed.


Incidence and Mortality of Colorectal Cancer and Relationships with the Human Development Index across the World.
This study aimed to investigate the standardized incidence and mortality rate of colorectal cancer and its relationship with the human development index (HDI) across the world in 2012. This ecologic study was conducted for assessment of the correlation between age-specific incidence rate (ASIR) and age-specific mortality rate (ASMR) with HDI and its components. Data for SIR and SMR for every country for the year 2012 were obtained from the global cancer project. We used a bivariate method for assessment of the correlation between SIR and SMR and HDI. Statistical significance was assumed at <0.05. Statistical analyses were performed using SPSS (Version 22.0, SPSS Inc.). Countries with the highest SIR of colorectal cancer in the world in 2012, were Republic of Korea, Slovakia, Hungary and countries with the highest SMR were Hungary, Croatia and Slovakia. The correlation between SIR of colorectal cancer and the HDI was 0.712 (P≤0.001), with life expectancy at birth 0.513 (P≤0.001), with mean years of schooling 0.641 (P≤0.001) and with level of income per each person of the population 0.514 (P=0.013). In addition, the correlation between SMR of colorectal cancer and the HDI was 0.628 (P≤0.001), with life expectancy at birth 0.469 (P≤0.001), with mean years of schooling 0.592 (P≤0.001) and with level of income per each person of the population 0.378 (P=0.013). The highest SIR and SMR of colorectal cancer was in the WHO Europe region. There was a positive correlation between HDI and SIR and SMR of colorectal cancer.


Cephalometric norms for a Moroccan population.
This is a descriptive cephalometric study aimed at contributing to the establishment of Steiner analysis cephalometric norms for a patient population from the Center for Dental Treatment and Consultation (CCTD) at the Ibn Rochd Hospital Center in Casablanca, Morocco. Teleradiography was used to obtain lateral cephalograms of 71 young adults (47 women; 24 men) aged on average 22.73 ± 1.69 years. All subjects presented good facial harmony, an acceptable profile, and dental class I with no history of orthodontic treatment. Tracing and analysis followed. The resulting means and standard deviations were compared to Steiner's norms and norms from similar studies. This revealed certain particularities in our sample, the most notable being a greater skeletal sagittal discrepancy (indicating a class II tendency), labial crown tipping of the lower incisors, and a retruded position of the maxillary and mandibular bony bases. These features should be taken into account when diagnosing and treating patients at the CCTD. However, more exhaustive studies must be performed before these results can be generalized to the Casablancan or Moroccan populations as a whole.


Bronchopulmonary dysplasia: Pathophysiology and potential anti-inflammatory therapies.
Inflammation of the preterm lungs is key to the pathogenesis of bronchopulmonary dysplasia (BPD), whether it arises as a consequence of intrauterine inflammation or postnatal respiratory management. This review explores steroidal and non-steroidal therapies for reducing neonatal pulmonary inflammation, aimed at treating or preventing BPD.


Evaluating the impact of in silico predictors on clinical variant classification.
According to the American College of Medical Genetics and Genomics/Association of Medical Pathology (ACMG/AMP) guidelines, in silico evidence is applied at the supporting strength level for pathogenic (PP3) and benign (BP4) evidence. Although PP3 is commonly used, less is known about the effect of these criteria on variant classification outcomes. A total of 727 missense variants curated by Clinical Genome Resource expert groups were analyzed to determine how often PP3 and BP4 were applied and their impact on variant classification. The ACMG/AMP categorical system of variant classification was compared with a quantitative point-based system. The pathogenicity likelihood ratios of REVEL, VEST, FATHMM, and MPC were calibrated using a gold standard set of 237 pathogenic and benign variants (classified independent of the PP3/BP4 criteria). The PP3 and BP4 criteria were applied by Variant Curation Expert Panels to 55% of missense variants. Application of those criteria changed the classification of 15% of missense variants for which either criterion was applied. The point-based system resolved borderline classifications. REVEL and VEST performed best at a strength level consistent with moderate evidence. We show that in silico criteria are commonly applied and often affect the final variant classifications. When appropriate thresholds for in silico predictors are established, our results show that PP3 and BP4 can be used at a moderate strength.


Adaphostin and other anticancer drugs quench the fluorescence of mitochondrial potential probes.
Fluorescent dyes are widely used to monitor changes in mitochondrial transmembrane potential (DeltaPsim). When MitoTracker Red CMXRos, tetramethylrhodamine methyl ester (TMRM), and 3,3'dihexyloxacarbocyanine iodide (DiOC6(3)) were utilized to examine the effects of the experimental anticancer drug adaphostin on intact cells or isolated mitochondria, decreased fluorescence was observed. In contrast, measurement of tetraphenylphosphonium uptake by the mitochondria using an ion-selective microelectrode failed to show any effect of adaphostin on DeltaPsim. Instead, further experiments demonstrated that adaphostin quenches the fluorescence of the mitochondrial dyes. Structure-activity analysis revealed that the adamantyl and p-aminobenzoic acid moieties of adaphostin are critical for this quenching. Anticancer drugs containing comparable structural motifs, including mitoxantrone, aminoflavone, and amsacrine, also quenched the mitochondrial probes. These results indicate the need for caution when mitochondrial dyes are utilized to examine the effects of xenobiotics on DeltaPsim and suggest that some previously reported direct effects of anticancer drugs on mitochondria might need re-evaluation.


Hyperchloremia - Why and how.
Hyperchloremia is a common electrolyte disorder that is associated with a diverse group of clinical conditions. The kidney plays an important role in the regulation of chloride concentration through a variety of transporters that are present along the nephron. Nevertheless, hyperchloremia can occur when water losses exceed sodium and chloride losses, when the capacity to handle excessive chloride is overwhelmed, or when the serum bicarbonate is low with a concomitant rise in chloride as occurs with a normal anion gap metabolic acidosis or respiratory alkalosis. The varied nature of the underlying causes of the hyperchloremia will, to a large extent, determine how to treat this electrolyte disturbance.


Chromatographic and histochemical identification of dopamine within an identified neuron in the leech nervous system.
Each segmental ganglion of the leech nervous system has two pairs of lateral roots extending to the body wall and viscera. A cluster of about eight neuron cell bodies is located proximal to the first major branch of each anterior root and is termed the anterior root ganglion (ARG). Only one of these eight cells is vitally-stained by Neutral Red dye and fluoresces an intense blue-green following the glyoxylic acid histochemical condensation. The emission spectrum of this anterior root cell (AR) is stable under continuous UV illumination and is bimodal, with peaks at about 480 and 515 nm. This spectrum is indistinguishable from that of millimolar solutions of dopamine (DA) in gelatin droplets following glyoxylic acid histochemistry. We utilized high performance liquid chromatography and an amperometric detector to measure DA within the AR neurosomata at 1.01 pmol/cell. The AR cells in this study had an average diameter of 23 micron and therefore, the minimum intrasomatal concentration of DA is 160 mM, an unusually high level for any neurotransmitter. We measured DA in anterior axons at 0.83 pmol, in segmental ganglia at 1.07 pmol, and in longitudinal connectives at 0.16 pmol. Control neurosomata (Retzius cells) and axonal tracts which lack blue-green fluorescence (posterior and distal anterior roots), had no detectable DA (less than 0.06 pmol/sample). These data establish that the catecholamine DA is responsible for the fluorescence of the AR cell.


Scoliosis in dysplastic spondylolisthesis: a clinical survey of 50 young patients.
Dysplastic spondylolisthesis is a rare spinal deformity that occurs mainly in young patients. Although its sagittal parameters had been well stated, coronal abnormalities in these patients were poorly studied. The purposes of this study were: (1) to investigate the prevalence of scoliosis in dysplastic spondylolisthesis;(2) to assess scoliosis resolution or persistence after surgery; and (3) to propose a modified classification of scoliosis associated with dysplastic spondylolisthesis. Fifty patients (average age 14.9 ± 5.6 years) diagnosed with dysplastic spondylolisthesis who underwent surgical treatment were followed up and their data were analyzed. Standing posteroanterior and lateral full spine radiographs were used to measure the coronal and sagittal parameters. Patients with scoliosis, which was defined as a coronal Cobb angle greater than 10°, were divided into three groups according to their curve characteristics: "independent" scoliosis (IS) group, spasm scoliosis (SS) group, and olisthetic scoliosis (OS) group. SS and OS were spondylolisthesis-induced scoliosis. The radiographic parameters and patient-reported outcomes were collected before and after surgery and compared between groups. The average slip percentage was 62.8% ± 23.1% and the average follow-up time was 51.5 ± 36.4 months (range 3-168 months). Twenty-eight of the 50 (56%) dysplastic spondylolisthesis patients showed scoliosis, of which 8 were IS (24.7° ± 15.2°), 11 were SS (13.9° ± 3.0°), and 9 were OS (12.9° ± 1.9°). By the last follow-up, no scoliosis resolution was observed in the IS group whereas all SS patients were relieved. Of the nine patients with OS, four (44.4%) had scoliosis resolution after surgery. Distinguishing different types of scoliosis in dysplastic spondylolisthesis patients may help surgeons to plan treatment and understand prognosis. For patients with significant scoliosis, whether "independent" or spondylolisthesis-induced, treatment of spondylolisthesis should be performed first and scoliosis should be observed for a period of time and treated according to the corresponding principles.


A case-crossover study of ambient particulate matter and cardiovascular and respiratory medical encounters among US military personnel deployed to southwest Asia.
To evaluate the impact of ambient particulate matter (PM) on acute cardiorespiratory morbidity among US military personnel in southwest Asia. We linked ambient PM data collected between December 2005 and June 2007 with personnel, medical, and meteorological data. We implemented a case-crossover analysis to estimate base-specific associations and pooled those estimates using meta-analytic methods. The adjusted odds ratios for a 10-μg/m increase in ambient PM2.5 and a qualifying medical encounter were 0.92 (95% confidence interval [CI]: 0.77 to 1.11) and 1.01 (95% CI: 0.95 to 1.07) for the current (lag_0) and previous (lag_1) days. The estimates for a 10-μg/m increase in PM10 were 0.99 (95% CI: 0.97 to 1.03) at lag_0, and 1.00 (95% CI: 0.97 to 1.02) at lag_1. No statistically significant associations between PM and cardiorespiratory outcomes were observed in this young, relatively healthy, deployed military population.


Examination stress in Singapore primary schoolchildren: how compliance by subjects can impact on study results.
Examinations are anecdotally viewed as extremely stressful to Singapore schoolchildren. We test this postulate by obtaining parental ratings of children's emotional stress levels longitudinally in a large representative sample of sixth (P6) and fifth (P5) class primary schoolchildren, respectively, exposed and unexposed to a streaming examination. Children's stress levels were rated monthly by a parent for 10 months. Analyses failed to find evidence of any differential stress impact across P6 and P5 comparison groups, apart from a subset of P6 children whose parents complied with every monthly survey. The streaming examination in the final year of primary school did not emerge as a general stressor to children, but achieved salience within a defined subset of children whose parents were highly study compliant. Study compliance may be a proxy variable of some import, and have wider relevance to other cohort studies and to intervention trials.


Cardiovascular medication after cancer at a young age in Finland: A nationwide registry linkage study.
Despite improved survival rates, childhood and young adult (YA) cancer survivors face elevated risks for life-threatening morbidities, especially cardiovascular complications. Our nationwide Finnish registry study investigated the purchases of cardiovascular medication from 1993 to 2011 in patients diagnosed with cancer aged below 35 years (N = 8,197) between 1993 and 2004 compared to siblings (N = 29,974) via linkage to the drug purchase registry. The cumulative incidence for purchasing cardiovascular medications was higher in childhood and YA cancer patients compared to siblings with a rising trend over time. After childhood cancer, the highest hazard ratio (HR) was found for purchasing anticoagulants (HR 19.8, 95% CI 8.5-45.9). The HRs for any cardiovascular medication (HR 7.2, 95% CI 5.1-10.1) and cardiac medication (HR 4.8, 95% CI 3.3-6.9) were markedly elevated after childhood cancer as well. Regarding YA cancer patients, the respective HRs were 2.5 (95% CI 2.0-3.2) for anticoagulants, HR 1.7 (95% CI 1.5-1.9) for any cardiovascular medication and HR 1.5 (95% CI 1.3-1.7) for cardiac medication. Among cancer patients, highest HRs for cardiovascular medication were observed after childhood acute lymphoblastic leukemia (ALL) and bone tumors (HR 10.2, 95% CI 6.8-15.5 and HR 7.4, 95% CI 4.0-13.7) and YA ALL and acute myeloid leukemia (HR 5.1, 95% CI 3.5-7.1 and HR 2.8, 95% CI 1.8-4.0). Our study demonstrated increased HRs for purchasing cardiovascular medication after early-onset cancer compared to siblings reflecting elevated cardiovascular morbidity. Thus, the implementation of long-term cardiovascular disease screening is imperative to prevent, detect and adequately treat cardiovascular late effects after cancer at a young age.


Damage by episodic flooding to Phragmites reeds in a prealpine lake: proposal of a model.
The development of lakeside fringes of Phragmites reeds can be affected by high water levels, leading in extreme cases to die-back. A model is presented that allows estimation of the proportions of the damage. The model-formulated for 1 year and one Phragmites stalk-is based on the growth curve of the stalk, the altitude of the growth site, and the water level curve for the year. Applied to a reed stand over a series of years, the model is based upon the frequency distribution of the critical stalk length and the chance that the water level will be below a given value, each parameter being time dependent. Three case studies from Lake Constance-Untersee provide an example of the significance of episodic high water levels. Hence, aestival high water levels are expected to be one of the main factors controlling the lakeside frontline of the reedbelt. The model can be used in waterworks engineering, where reed plantations are to be established on the shores of lakes and reservoirs with strongly fluctuating water levels.


A cytogenetic description of a new species of the Anopheles culicifacies complex.
Cytogenetic observations on an extensive material of the Anopheles culicifacies complex from the Thenpennai river area, Tamil Nadu, South India show that the populations are made up of four cytologically distinct species. Three of these, labeled A, B and C have already been described. A fourth one, monomorphic for the inversion arrangement +a +b in the X chromosome and il + hl in the second chromosome, is designated as D, another morphologically indistinguishable sibling species. Each sibling species is characterized by a species-specific type of Y-chromosome. Both of these criteria, inversions and Y-chromosomes can be used to distinguish these important malaria vectors.


Central nervous system tumours among adolescents and young adults (15-39 years) in Southern and Eastern Europe: Registration improvements reveal higher incidence rates compared to the US.
To present incidence of central nervous system (CNS) tumours among adolescents and young adults (AYAs; 15-39 years) derived from registries of Southern and Eastern Europe (SEE) in comparison to the Surveillance, Epidemiology and End Results (SEER), US and explore changes due to etiological parameters or registration improvement via evaluating time trends. Diagnoses of 11,438 incident malignant CNS tumours in AYAs (1990-2014) were retrieved from 14 collaborating SEE cancer registries and 13,573 from the publicly available SEER database (1990-2012). Age-adjusted incidence rates (AIRs) were calculated; Poisson and joinpoint regression analyses were performed for temporal trends. The overall AIR of malignant CNS tumours among AYAs was higher in SEE (28.1/million) compared to SEER (24.7/million). Astrocytomas comprised almost half of the cases in both regions, albeit the higher proportion of unspecified cases in SEE registries (30% versus 2.5% in SEER). Similar were the age and gender distributions across SEE and SEER with a male-to-female ratio of 1.3 and an overall increase of incidence by age. Increasing temporal trends in incidence were documented in four SEE registries (Greater Poland, Portugal North, Turkey-Izmir and Ukraine) versus an annual decrease in Croatia (-2.5%) and a rather stable rate in SEER (-0.3%). This first report on descriptive epidemiology of AYAs malignant CNS tumours in the SEE area shows higher incidence rates as compared to the United States of America and variable temporal trends that may be linked to registration improvements. Hence, it emphasises the need for optimisation of cancer registration processes, as to enable the in-depth evaluation of the observed patterns by disease subtype.


Regulation of testis-specific carnitine transporter (octn3) gene by proximal cis-acting elements Sp1 in mice.
The mouse octn transporter family consists of three genes, octn1, octn2 and octn3. The gene products octn2 and octn3, which transport carnitine with high affinity, are both expressed in testis, where carnitine is required to maintain sperm cell motility. Here, we focused on the regulatory mechanism of the expression of octn3 in an attempt to determine whether the differential tissue expression profiles of the octn2 and octn3 genes reflect distinct physiological roles of octn2 and octn3. The promoter activity of the octn3 gene was examined by luciferase assay and gel mobility shift assay using the mouse Sertoli cell line TM4 as host cells. Deletion-mutant assay demonstrated that a gene segment of the 5'-untranslated region located at about -500 bp relative to the transcription start site is required for constitutive octn3 transcription. Deletion of the Sp1-binding site within the region resulted in loss of transcriptional activity. In addition, overexpression of Sp1 in TM4 cells led to a further increase of transcription of octn3. These results demonstrated that Sp1-binding sites are necessary and sufficient for constitutive octn3 gene transcription. Furthermore, the expressions of both of octn2 and octn3 genes in TM4 cells were up-regulated by palmitic acid, whereas carnitine increased only the expression of octn2 without any change in octn3 expression. Accordingly, the expressions of octn2 and 3 are regulated by distinct mechanisms, suggesting distinct roles of octn2 and octn3 in carnitine transport.


Ultrastructural changes of articular cartilage chondrocytes associated with freeze-thawing.
In an attempt to justify the use of cryopreserved versus fresh articular cartilage (AC) allografts, we used transmission electron microscopy (TEM) to study the ultrastructure of fresh versus frozen-thawed AC with or without a dimethyl sulfoxide (DMSO) treatment. AC explants were cut aseptically from the femoral condyles of healthy, mature rabbits when they were killed. Half of all explants were incubated in Ham's F-12 medium, supplemented with antibiotics and with or without 7.5% DMSO, frozen to -80 degrees C, stored for 24 h, and thawed rapidly. These, and the control explants, were fixed with glutaraldehyde, paraformaldehyde, and acrolein in cacodylate buffer. Sections were stained for acid phosphatase (APase), postfixed with osmium, embedded, and examined under TEM. The typical organization of the matrix and the cells was noted in control sections. The chondrocytes contained intact nuclei, organelles, and discrete plasma membrane. Although some endoplasmic reticula and nuclear membrane appeared intact, distinct ultrastructural changes were observed in frozen-thawed samples treated with DMSO. These changes included condensation of chromatin, large lipid droplets, partly disrupted plasma membrane, and pericellular precipitation of APase-positive crystalites. In sections not treated with DMSO, the cytoplasm was extensively vacuolated and no distinct organelles could be detected in the chondrocytes. Little difference was noted between the matrix organization of fresh or frozen-thawed samples. Our results suggest that distinct ultrastructural changes occur in the chondrocytes following freeze-thawing of intact AC and that DMSO pretreatment may contribute to improvement in the cryopreservation of AC.


Simple Stereoscopic Display of 3-Dimensional Living Heart Anatomy Relevant to Electrophysiological Practice.
Comprehensive appreciation of the 3-dimensional anatomy of the living heart is essential for accurate diagnosis and establishment of safe interventional treatment by clinical electrophysiologists. Three-dimensional images displayed on a 2-dimensional surface usually undergo distortion and are not considered a real 3-dimensional representation because they cannot provide accurate depth perception. Currently, the availability of 3-dimensional visualization techniques, including 3-dimensional printing, 3-dimensional projectors, 3-dimensional monitors, and virtual reality, is limited owing to their limited user-friendliness and high costs. The authors discuss an alternative conventional approach of a cross-eyed method for viewing stereoscopically displayed images for better appreciation of real 3-dimensional images based on a simple technique.


Buspirone decreases susceptibility to hypocapnic central sleep apnea in chronic SCI patients.
Spinal cord injury (SCI) is a risk factor for central sleep apnea (CSA). Previous studies in animal models with SCI have demonstrated a promising recovery in respiratory and phrenic nerve activity post-injury induced by the systemic and local administration of serotonin receptor agonists such as Buspirone and Trazodone. Human trials must be performed to determine whether individuals with SCI respond similarly. We hypothesized that Buspirone and Trazodone would decrease the propensity to hypocapnic CSA during sleep. We studied eight males with chronic SCI and sleep-disordered breathing (SDB) [age: 48.8 ± 14.2 yr; apnea-hypopnea index (AHI): 44.9 ± 23.1] in a single-blind crossover design. For 13 days, participants were randomly assigned either Buspirone (7.5-15 mg twice daily), Trazodone (100 mg), or a placebo followed by a 14-day washout period before crossing over to the other interventions. Study nights included polysomnography and induction of CSA using a noninvasive ventilation protocol. We assessed indexes of SDB, CO2 reserve, apneic threshold (AT), controller gain (CG), plant gain (PG), and ventilatory parameters. CO2 reserve was significantly widened on Buspirone (-3.6 ± 0.9 mmHg) compared with both Trazodone (-2.5 ± 1.0 mmHg, P = 0.009) and placebo (-1.8 ± 1.5 mmHg, P < 0.001) but not on Trazodone vs. placebo (P = 0.061). CG was significantly decreased on Buspirone compared with placebo (1.8 ± 0.4 vs. 4.0 ± 2.0 L/(mmHg·min), P = 0.025) but not on Trazodone compared with placebo (2.5 ± 1.1 vs. 4.0 ± 2.0 L/(mmHg·min); P = 0.065). There were no significant differences for PG, AT, or any SDB indexes (AHI, obstructive apnea index, central apnea index, oxygen desaturation index). The administration of Buspirone decreased the susceptibility to induced hypocapnic central apnea by reducing chemosensitivity and increasing CO2 reserve in chronic SCI patients.NEW & NOTEWORTHY This research study is novel as it is the first study in a humans that we are aware of that demonstrates the ability of Buspirone to increase CO2 reserve and hence decrease susceptibility to hypocapnic central apnea in patients with spinal cord injury.


Efficacy of three antimicrobial mouthwashes in reducing SARS-CoV-2 viral load in the saliva of hospitalized patients: a randomized controlled pilot study.
This study aimed to evaluate the efficacy of 3 mouthwashes in reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in the saliva of coronavirus disease 2019 (COVID-19) patients at 30 min, 1, 2 and 3 h after rinsing. This pilot study included 40 admitted COVID-19 positive patients (10 in each group). Saliva samples were collected before rinsing and at 30 min, 1, 2 and 3 h after rinsing with: Group 1-0.2% Chlorhexidine digluconate (CHX); Group 2-1.5% Hydrogen peroxide (H2O2); Group 3-Cetylpyridinium chloride (CPC) or Group 4 (control group)-No rinsing. Viral load analysis of saliva samples was assessed by Reverse Transcription quantitative PCR. Mean log10 viral load at different time points was compared to that at baseline in all groups using a random effects linear regression analysis while for comparison between groups linear regression analysis was used. The results showed that all groups had a significantly reduced mean log10 viral load both at 2 (p = 0.036) and 3 (p = 0.041) hours compared to baseline. However, there was no difference in mean log10 viral load between any of the investigated mouthwashes and the control group (non-rinsing) at the evaluated time points. Although a reduction in the SARS-CoV-2 viral load in the saliva of COVID-19 patients was observed after rinsing with mouthwashes containing 0.2% CHX, 1.5% H2O2, or CPC, the reduction detected was similar to that achieved by the control group at the investigated time points. The findings of this study may suggest that the mechanical action of rinsing/spitting results in reduction of SARS-CoV-2 salivary load.


Heavy Rainfall, Sewer Overflows, and Salmonellosis in Black Skimmers (Rynchops niger).
Extreme weather events, particularly heavy rainfall, are occurring at greater frequency with climate change. Although adverse human health effects from heavy rainfall are often publicized, impacts to free-ranging wildlife populations are less well known. We first summarize documented associations of heavy rainfall on wildlife health. We then report a novel investigation of a salmonellosis outbreak in a colony of black skimmers (Rynchops niger) in Florida, USA. During June-September 2016, heavy rainfall resulted in the discharge of millions of gallons of untreated wastewater into the Tampa Bay system, contaminating the water body, where adult skimmers foraged. At least 48 fledglings died, comprising 39% of the colony's nesting season's offspring. Of eight examined deceased birds from the colony, six had a systemic salmonellosis infection. Isolates were identified as Salmonella enterica serotype Typhimurium. Their pulsed-field gel electrophoresis patterns were identical to each other and matched those from several human Salmonella sp. infections. Differences among whole-genome sequences were negligible. These findings and the outbreak's epidemic curve suggest propagated transmission occurred within the colony. A multidisciplinary and One Health approach is recommended to mitigate any adverse effects of climate change-driven stochastic events, especially when they place already imperiled wildlife at further risk.


Unusual cause of short stature.
A 24-year-old man evaluated for paresthesias and short stature was found to be hypocalcemic on initial presentation. Further evaluation showed that he had a low-normal parathormone level by amino-terminal assay, medullary stenosis of the long bones, and multiple ophthalmologic abnormalities. The remainder of his pituitary function, including growth hormone response to insulin-induced hypoglycemia, was normal. As no family history of similar findings was evident, a sporadic case of Kenny's or Kenny-Caffey syndrome was diagnosed. He became normocalcemic in response to vitamin D and calcium carbonate therapy. The results of testing in this patient and the findings in other patients previously described with the Kenny-Caffey syndrome are reviewed.


Are transferrin and leucine aminopeptidase electromorphs reliable genetic markers in the prairie vole, Microtus ochrogaster?
The reliability of TF and LAP electromorphs as genetic markers in Microtus ochrogaster was examined by taking 18 voles captured in the wild during the summer and subjecting them to winter conditions for one month. During this time voles were bled each week and their plasma scored for TF and LAP phenotypes using starch gel electrophoresis. There were no changes in the mobility of the TF and LAP electromorphs in the same animal when fresh samples were used for electrophoresis. However, there were a few inconsistencies in scoring phenotypes when plasma was frozen for 10 weeks or longer. Reasons for the contradictory results obtained by McGovern and Tracy (1981) in the same species is discussed.


Air kerma rate from radionuclides distributed in forest ecosystem.
This study evaluates the air kerma rate in radioactively contaminated forests. The air kerma rates created by plane sources of monoenergetic photons in the energy range 0.02-3 MeV located at different depths in soil up to 50 g cm-2 and at different heights in the forest medium from 0.05 to 50 m were calculated using numeric solution of the transport (Boltzmann) equation. To simplify the practical use of the results obtained by solving the Boltzmann equation, the study additionally includes approximation formulae for calculating air kerma rate separately from contaminated soil, crowns and trunks of trees in a forest ecosystem for 20 radionuclides - fission products that significantly contribute to the external dose. Biomaterial of trunks and crowns was modeled as uniformly distributed in corresponding layers and homogeneously mixed with air. Different distributions of radionuclides in soil were considered including plane source located at different depths, exponential and uniform distribution. Based on the results, the effect of forest biomass presence as an absorbing and scattering medium on the air kerma rate at 1 m above soil was evaluated. The estimated relative difference in air kerma rate at 1 m above soil in the forest medium and in free air for monoenergetic photon sources with energies 0.1 MeV, 0.66 MeV and 3 MeV did not correlate significantly with the energy of photons. Its maximum value in forest medium with biomass density of 5 kg m-3 was 15-20% for the source at soil depth ∼0.3 g cm-2, decreasing to less than 5% when it is at soil depth greater than 7 g cm-2. An example calculation of the air kerma rate dynamics is presented for the initial period after radioactive fallout considering weathering processes (rainfall and wind action) that contribute to the transfer of activity from the canopies to the forest floor. The differences in air kerma rate values, as an integral characteristic of the gamma radiation field from a radioactive cloud in the forest and in the open area, were evaluated.


Characterization of laser-driven proton acceleration from water microdroplets.
We report on a proton acceleration experiment in which high-intensity laser pulses with a wavelength of 0.4 μm and with varying temporal intensity contrast have been used to irradiate water droplets of 20 μm diameter. Such droplets are a reliable and easy-to-implement type of target for proton acceleration experiments with the potential to be used at very high repetition rates. We have investigated the influence of the laser's angle of incidence by moving the droplet along the laser polarization axis. This position, which is coupled with the angle of incidence, has a crucial impact on the maximum proton energy. Central irradiation leads to an inefficient coupling of the laser energy into hot electrons, resulting in a low maximum proton energy. The introduction of a controlled pre-pulse produces an enhancement of hot electron generation in this geometry and therefore higher proton energies. However, two-dimensional particle-in-cell simulations support our experimental results confirming, that even slightly higher proton energies are achieved under grazing laser incidence when no additional pre-plasma is present. Illuminating a droplet under grazing incidence generates a stream of hot electrons that flows along the droplet's surface due to self-generated electric and magnetic fields and ultimately generates a strong electric field responsible for proton acceleration. The interaction conditions were monitored with the help of an ultra-short optical probe laser, with which the plasma expansion could be observed.


Desmethylnafoxidine aziridine: an electrophilic affinity label for the estrogen receptor with high efficiency and selectivity.
Desmethylnafoxidine aziridine (Naf-Az), an affinity label for the estrogen receptor based structurally on the antiestrogen nafoxidine, has been prepared in unlabeled and in high specific activity, tritium-labeled form and has been evaluated for its apparent competitive binding, and time-dependent irreversible, covalent attachment to the estrogen receptor. Naf-Az was synthesized through a key 1,2-diaryl-3,4-dihydronaphthalene intermediate that was prepared from 6-methoxy-1-tetralone by two routes involving alternate strategies for arylation. Conversion of the diaryldihydronaphthalene to Naf-Az through a series of deprotection-activation reactions culminated in ethyleneimine displacement of a methanesulfonate. The tritium-labeled material was prepared by tritium-iodine exchange on an iodinated methanesulfonate precursor, followed by ethyleneimine displacement. Compared to our previously-prepared reagent tamoxifen aziridine (Tam-Az), Naf-Az has a higher apparent competitive binding affinity, and it reacts with the estrogen receptor in cytosol preparations and in intact MCF-7 breast cancer cells rapidly and with at least comparable efficiency and selectivity. SDS-polyacrylamide gel electrophoretic analysis confirms its selective labeling of the Mr 66,000 estrogen receptor. Naf-Az should prove to be useful in studies aimed at characterizing the properties and structure of estrogen receptors.


A novel procedure for phase separation in dispersive liquid-liquid microextraction based on solidification of the aqueous phase.
In this paper, an alternative for handling the organic phase after a dispersive liquid-liquid microextraction using organic solvents lighter than water is presented. It is based on solidification (at -18°C) of the aqueous phase obtained after centrifugation, and the decantation, collection and analysis of the liquid organic layer. The extraction of nicotine in toluene, and its determination in eggplant samples was conducted as a proof of concept. The study has been carried out using standards prepared in water and the formation of the dispersion was assisted by sonication. The organic extract was analysed using gas chromatography coupled to mass spectrometry. Satisfactory analytical figures of merit as: limit of detection (0.4µgL(-1), 2ngg(-1) wet sample), limit of quantification (1.2µgL(-1), 6.5ngg(-1) wet sample), within-day precision (RSD=7%), and linearity interval (up to 384µgL(-1) nicotine) were achieved. It constituted a contribution to the handling of organic extracts after microextraction processes.


Absence of mutagenicity of benzo[c]phenanthridine alkaloids in somatic cells of Drosophila melanogaster: comparison with 7,12-dimethylbenz[a]anthracene and chrysene.
The wing somatic mutation and recombination test (SMART) of Drosophila melanogaster was used to study the mutagenic potential of three benzo[c]phenanthridines with antileukemic properties, fagaronine, nitidine and O-methylfagaronine, as compared with that of two structurally related aromatic polycyclic hydrocarbons: 7,12-dimethylbenz[a]anthracene and chrysene. Although toxic to larvae, the benzo[c]phenanthridines and chrysene gave negative or inconclusive results while 7,12-dimethylbenz[a]anthracene was found to be highly mutagenic and recombinogenic as previously reported. These results suggest that the alkoxy groups and the quaternary nitrogen of the benzo[c]-phenanthridines may reduce or eliminate their mutagenicity in spite of their similarity to methylated polycyclic aromatic hydrocarbons.


Occurrence of carpal osteoarthritis after treatment of scaphoid nonunion with bone graft and herbert screw: a long-term follow-up study.
To determine the occurrence, progression, and clinical results of osteoarthritis (OA) after bone grafting and Herbert screw fixation for scaphoid nonunion. Fifty patients were reviewed (mean follow-up period, 12.0 +/- 1.6 y) to analyze degenerative changes of the wrist after use of Herbert screws for scaphoid nonunion. Radiologic signs of OA were observed in 15 of 50 patients before surgery and in 23 of 50 after 10 years or more. The majority of degenerative changes were low grade. No OA at follow-up evaluation was seen in 27 of 35 patients with no preoperative degenerative changes. In 6 of 8 patients with OA its occurrence was either subsequent to concomitant injury, occurred after incorrect scaphoid reconstruction, or was caused by persistent nonunion. Of 15 wrists with OA at the time of surgery 9 remained unchanged and 6 increased in severity. Healing of nonunion was achieved in 42 of 50. Range of motion, however, was reduced to 88% of that of the opposite hand. At follow-up evaluation the mean Disabilities of the Arm, Shoulder, and Hand score was 9 +/- 13 and the mean Cooney score was 80 +/- 10. The results show high patient satisfaction and good function after healing of scaphoid nonunion. In the long term correct anatomic reconstruction of the nonarthritic carpus with a Herbert screw prevents onset of OA in most patients.


Mechanical properties of porcine spinal dura mater and pericranium.
The objective of this study was to characterize and compare the mechanical properties of porcine pericranium and spinal dura mater, to evaluate the mechanical suitability of pericranium as a dural graft. Eighty-eight spinal dura (cervical, thoracic, and lumbar regions, in ventral longitudinal, dorsal longitudinal and circumferential orientations) and eighteen pericranium samples (ventral-dorsal, and lateral orientations) from four pigs, were harvested and subjected to uniaxial loading while hydrated. The stiffness, strain at toe-linear regions transition, strain at linear-yield regions transition and other structural and mechanical properties were measured. Stress-strain curves were fitted to a one-term Ogden model and Ogden parameters were calculated. Linear regression models with cluster-robust standard errors were used to assess the effect of region and orientation on material and structural properties. Both spinal dura and pericranium exhibited distinct anisotropy and were stiffer in the longitudinal direction. The tissues exhibited structural and mechanical similarities especially in terms of stiffness and strains in the linear region. Stiffness ranged from 1.28 to 5.32 N/mm for spinal dura and 2.42-3.90 N/mm for pericranium. In the circumferential and longitudinal directions, the stiffness of spinal dura specimens was statistically similar to that of pericranium in the same orientation. The strain at the upper bound of the linear region of longitudinal pericranium (28.0%) was statistically similar to that of any spinal dura specimens (24.4-32.9%). Autologous pericranium has advantageous physical properties for spinal duraplasty. The present study demonstrated that longitudinally oriented pericranium is mechanically compatible with spinal duraplasty procedures. Autologous pericranium grafts will likely support the mechanical loads transmitted from the spinal dura, but further biomechanical analyses are required to study the effect of the lower yield strain of circumferential pericranium compared to spinal dura. Finally, the Ogden parameters calculated for pericranium, and the spinal dura at each spinal level, will be useful for computational models incorporating these soft tissues.


Comprehensive analysis of circular RNAs in pathological states: biogenesis, cellular regulation, and therapeutic relevance.
Circular RNAs (circRNAs) are members of the non-coding transcriptome; however, some of them are translated into proteins. These transcripts have important roles in both physiological and pathological mechanisms due to their ability to directly influence cellular signaling pathways. Specifically, circRNAs are regulators of transcription, translation, protein interaction, and signal transduction. An increased knowledge within their area is observed over the last few years, concomitant with the development of next-generation sequencing techniques. circRNAs are mostly tissue and disease specific with the ability of specifically changing the biological behavior of cells. The altered expression profile is currently investigated as novel minimally invasive diagnosis/prognosis tool and also therapeutic target in human disease. The diagnosis approach is based on their level modification within pathological states, especially cancer, where circRNAs' therapies are intensively explored in anti-aging strategies, diabetes, cardiovascular diseases, and malignant pathologies, and are relying on the restoration of homeostatic profiles.


FreeSurfer 7 quality control: Key problem areas and importance of manual corrections.
We have studied the effects of manual quality control of brain Magnetic Resonance Imaging (MRI) images processed with Freesurfer. T1 images of first episode psychosis patients (N = 60) and healthy controls (N = 41) were inspected for gray matter boundary errors. The errors were fixed, and the effects of error correction on brain volume, thickness, and surface area were measured. It is commonplace to apply quality control to Freesurfer MRI recordings to ensure that the edges of gray and white matter are detected properly, as incorrect edge detection leads to changes in variables such as volume, cortical thickness, and cortical surface area. We find that while Freesurfer v7.1.1. does regularly make mistakes in identifying the edges of cortical gray matter, correcting these errors yields limited changes in the commonly measured variables listed above. We further find that the software makes fewer gray matter boundary errors when processing female brains. The results suggest that manually correcting gray matter boundary errors may not be worthwhile due to its small effect on the measurements, with potential exceptions for studies that focus on the areas that are more commonly affected by errors: the areas around the cerebellar tentorium, paracentral lobule, and the optic nerves, specifically the horizontal segment of the middle cerebral artery.


Laparoscopic trans-peritoneal hernioplasty (TAPP) is useful for obturator hernias: report of a case.
A 71-year-old female presented to our hospital due to pain from the right hip joint to the lower abdomen. The pain had suddenly appeared and spontaneously disappeared more than 10 times during the past 2 years. She had visited many hospitals, but remained undiagnosed. The patient underwent a computed tomography (CT) scan of the pelvis, and a soft tissue shadow was seen between the external obturator and pectineal muscles. She was diagnosed with a right obturator hernia and underwent elective repair by laparoscopic trans-peritoneal hernioplasty (TAPP). 1 year has passed since the surgery, without any recurrence of the abdominal pain. Obturator hernias are rare, and most cases are found as incarcerated hernias. It is rare to find an obturator hernia without intestinal obstruction, or with the recurrent pain as in our case. We herein report a case in which an obturator hernia was undiagnosed and intermittent pain was experienced for 2 years prior to TAPP, which appears to have successfully treated the hernia.


Zoonotic microsporidia in dogs and cats in Poland.
This study investigated the prevalence, genetic diversity, and zoonotic concerns of microsporidia in household dogs and cats in Poland. A total of 126 (82 dogs and 44 cats) fecal specimens were analyzed for the presence of specific DNA of Enterocytozoon bieneusi and Encephalitozoon spp. using a nested PCR protocol amplifying the internal transcribed spacer region of the rRNA gene. Microsporidia were found in 10 (7.9%) out of the 126 examined stool samples. Of the 82 dogs, 4 (4.9%) and 2 (2.4%) were positive for E. bieneusi (genotypes D and PtEbIX) and Encephalitozoon cuniculi genotype II, respectively. Of the 44 cats, 4 (9.1%) were positive for E. bieneusi (genotypes PtEbIX and eb52). Additionally, one cat (2.3%) was concurrently infected with E. bieneusi (PtEbIX) and E. cuniculi (genotype II). Considering that all detected microsporidia in dogs and cats have been previously associated with human microsporidiosis, companion animals may be a potential source of microsporidia infections in humans.


The new SRS/FSRT technique HyperArc for benign brain lesions: a dosimetric analysis.
To evaluate the potential benefit of HyperArc (HA) fractionated stereotactic radiotherapy (FSRT) for the benign brain lesion. Sixteen patients with a single deep-seated, centrally located benign brain lesion treated by CyberKnife (CK, G4 cone-based model) were enrolled. Treatment plans for HA with two different optimization algorithms (SRS NTO and ALDO) and coplanar RapidArc (RA) were generated for each patient to meet the corresponding treatment plan criteria. These four FSRT treatment plans were divided into two groups-the homogeneous delivery group (HA-SRS NTO and coplanar RA) and the inhomogeneous delivery group (HA-ALDO and cone-based CK)-to compare for dosimetric outcomes. For homogeneous delivery, the brain V5, V12, and V24 and the mean brainstem dose were significantly lower with the HA-SRS NTO plans than with the coplanar RA plans. The conformity index, high and intermediate dose spillage, and gradient radius were significantly better with the HA-SRS NTO plans than with the coplanar RA plans. For inhomogeneous delivery, the HA-ALDO exhibited superior PTV coverage levels to the cone-based CK plans. Almost all the doses delivered to organs at risk and dose distribution metrics were significantly better with the HA-ALDO plans than with the cone-based CK plans. Good dosimetric distribution makes HA an attractive FSRT technique for the treatment of benign brain lesions.


High-voltage electrical injury: acute pathophysiology.
A reproducible high-voltage electrical injury model was established in the primate using a new approach to energy administration, measurement instrumentation, and data acquisition. Patterns of current repartition and temperature generation were examined in 24 primates. The predominant current load was carried in muscle, which is the tissue group occupying the largest cross-sectional area. Highest temperature values observed were in muscles of small cross-sectional diameter and in tissues of high inherent resistance. Surgeons should be aware of the principles and the pattern of current distribution when performing early debridement and/or definitive coverage procedures.


Using quality-control analysis of peak expiratory flow recordings to guide therapy for asthma.
To compare the action points in published asthma management plans with those derived from quality-control analysis of peak expiratory flow recordings. Longitudinal observational study. An ambulatory asthma education and management program in a tertiary care hospital. 35 adults with asthma and exacerbation of asthma. Peak expiratory flow diaries and symptom recordings. Asthma action points from published asthma management guidelines had poor operating characteristics. The success rate was 35% when the action point was a peak expiratory flow rate less than 60% of the patient's best peak flow. The success rate improved to 88% when the action point was a peak expiratory flow rate less than 80% of the patient's best peak flow. Published action points had a high failure rate. Peak flow decreased to below the published action points during a stable period of asthma in 7% to 51% of patients studied. Action points defined using quality-control analysis did significantly better. A peak flow value less than 3 standard deviations below the patient's mean peak flow detected 84% of exacerbations and had a low failure rate (19%). Other quality-control tests had sensitivities of 91% and 71%. Quality-control action points could detect exacerbations up to 4.5 days earlier than conventional methods. Individualized action points can be derived for patients with asthma by applying quality-control analysis to peak flow recordings. These action points are more sensitive in detecting exacerbations of asthma and have fewer false-positive results. Action plans developed in this manner should be more useful for the early detection of deteriorating asthma.


Ecofriendly polysaccharide-based alginate/pluronic F127 semi-IPN hydrogel with magnetic collectability for precise release of pesticides and sustained pest control.
Controlled-release systems are crucial for efficient pesticide utilization and environmental protection in agricultural production. The utilization of polysaccharide-based materials derived from biopolymers as carriers for controlling pesticide release holds significant potential. In this work, a reversible near infrared-responsive polysaccharide-based hydrogel (RNPH) was fabricated by employing a semi-interpenetrating polymer network (alginate-FeIII/pluronic F127) as a carrier to encapsulate Fe3O4@polydopamine (FP) and emamectin benzoate (EB)-loaded hollow mesoporous silica. The incorporation of FP into the RNPH introduced a photothermal effect, enabling the precise release of EB through reversible shrinkage of the hydrogel upon NIR irradiation. Additionally, the presence of magnetic Fe3O4 in the system facilitated the rapid removal of remaining RNPH from the environment using a magnet, reducing EB residue. Importantly, RNPH exhibited exceptional controlled-release performance and could be reused for at least 4 cycles. Furthermore, the anti-photolysis ability of EB protected by RNPH was enhanced by 4.8 times compared to EB alone. Moreover, RNPH significantly improved the adhesion of EB to foliar surfaces, thereby reducing the loss of EB while ensuring crop safety. Therefore, the polysaccharide-based hydrogel holds promise as a versatile carrier for the precise release of EB, offering valuable applications in enhancing pesticide bioavailability and promoting environmental safety.


H∞ State Estimation for Neural Networks With General Activation Function and Mixed Time-Varying Delays.
This article deals with H∞ state estimation of neural networks with mixed delays. In order to make full use of delay information, novel delay-product Lyapunov-Krasovskii functional (LKF) by using parameterized delay interval is first constructed. Then, generalized free-weighting-matrix integral inequality is used to estimate the derivative of LKF to reduce the conservatism. Also, a more general activation function is further applied by combining with parameterized delay interval in order to obtain a more accurate estimator model. Finally, sufficient conditions are derived to confirm that the estimation error system is asymptotically stable with a prescribed H∞ performance. Numerical examples are simulated to show the benefits of our proposed method.


A novel therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation.
Cell therapies that invoke pleiotropic mechanisms may facilitate functional recovery in patients with stroke. Based on previous experiments using microglia preconditioned by oxygen-glucose deprivation, we hypothesized that the administration of peripheral blood mononuclear cells (PBMCs) preconditioned by oxygen-glucose deprivation (OGD-PBMCs) to be a therapeutic strategy for ischemic stroke. Here, OGD-PBMCs were identified to secrete remodelling factors, including the vascular endothelial growth factor and transforming growth factor-β in vitro, while intra-arterial administration of OGD-PBMCs at 7 days after focal cerebral ischemia prompted expression of such factors in the brain parenchyma at 28 days following focal cerebral ischemia in vivo. Furthermore, administration of OGD-PBMCs induced an increasing number of stage-specific embryonic antigen-3-positive cells both in vitro and in vivo. Finally, it was found to prompt angiogenesis and axonal outgrowth, and functional recovery after cerebral ischemia. In conclusion, the administration of OGD-PBMCs might be a novel therapeutic strategy against ischemic stroke.


Expression of extracellular matrix metalloprotease inducer in laryngeal squamous cell carcinoma.
Head and neck cancer tumor cell invasion is responsible for both local destruction and distant metastasis. Invasion is largely mediated by matrix metalloproteases that are thought to be induced by tumor cell derived extracellular matrix metalloprotease inducer (EMMPRIN) in surrounding fibroblasts. We hypothesize that EMMPRIN is overexpressed in laryngeal cancer. Retrospective analysis of patients with supraglottic laryngeal cancer. Total protein immunoblotting and immunohistochemical analysis of normal and malignant tissue were performed to determine EMMPRIN expression. EMMPRIN immunoreactivity in 33 patients was correlated with clinicopathological features and survival. Whole-tissue lysates of tumors (n = 8) and metastatic lymph nodes (n = 2), but not normal skin (n = 8) or mucosa (n = 6), expressed significant amounts of EMMPRIN by immunoblotting. EMMPRIN membrane immunoreactivity (transmembrane EMMPRIN score) was associated with nodal positivity (P =.07), and it was a borderline significant predictor of survival (Hazards Ratio = 2.4; 95% CI, 0.88-6.55). As a categorical variable, higher transmembrane EMMPRIN score was associated with higher mortality. The present study helps to establish EMMPRIN as a widely expressed protein in dysplastic mucosa and supraglottic laryngeal cancer, but not in normal epithelial counterparts.


Therapeutic targets in the brain for overactive bladder: A focus on angiotensin II type 1 receptor.
Overactive bladder is a condition that affects both men and women, and significantly affects patients' quality of life. Anticholinergics, β3-adrenoceptor agonists, and botulinum toxin are currently being used for treatment. However, several patients do not respond to these medications or discontinue them because of adverse events. Angiotensin II (Ang II) is a neuropeptide produced in both brain and peripheral tissues, and Ang II type 1 (AT1) receptors, which are important regions for the micturition reflex, are widely expressed in the cerebral cortex, paraventricular nucleus, solitary tract nucleus, and periaqueductal gray. Our data showed that cumulative central Ang II administration, even at low doses, shortened the intercontraction interval without affecting the blood pressure or blood catecholamine levels. Additionally, Ang II can enhance the micturition reflex by suppressing the GABAergic nervous system and stimulating the downstream pathway of the AT1 receptor. The peripherally administered AT1 receptor blocker telmisartan inhibited central Ang II-induced facilitation of the micturition reflex. Targeting the central AT1 receptor may be a potential treatment approach for patients with overactive bladder. This review introduces the brain AT1 receptor as a therapeutic target in overactive bladder.


Purification of mammalian telomeric DNA for single-molecule analysis.
Here we provide a detailed protocol for the enrichment of telomeric repeats from mouse and human cells. The procedure consists of two successive rounds of digestion with frequently cutting restriction enzymes followed by size fractionation. Around 2 mg of genomic DNA is required, and the procedure lasts 5-6 d and yields preparations enriched >800-fold in telomeres. The purified material is suitable for single-molecule analysis of telomere structure, visualizing telomere replication and recombination intermediates by electron microscopy or performing molecular combing at telomeric repeats. No special skills are required for the enrichment procedure, while some assistance is needed in harvesting a large number of plates in a timely fashion at the beginning of the procedure. A smaller-scale version of the protocol that involves one round of digestion and purification requires 200 µg of DNA and enriches telomeres ~50-fold in 4 d is also provided. The latter can be combined with specific labeling for single-molecule analysis of replicating DNA or for long-read sequencing analysis of telomeric repeats. The procedure described here can be adapted to the enrichment of other repetitive elements, based on the use of restriction enzymes that do not cut into the repeat of interest.


Object-centered population coding in CA1 of the hippocampus.
Objects and landmarks are crucial for guiding navigation and must be integrated into the cognitive map of space. Studies of object coding in the hippocampus have primarily focused on activity of single cells. Here, we record simultaneously from large numbers of hippocampal CA1 neurons to determine how the presence of a salient object in the environment alters single-neuron and neural-population activity of the area. The majority of the cells showed some change in their spatial firing patterns when the object was introduced. At the neural-population level, these changes were systematically organized according to the animal's distance from the object. This organization was widely distributed across the cell sample, suggesting that some features of cognitive maps-including object representation-are best understood as emergent properties of neural populations.


HELLP syndrome manifesting as abnormal fetal umbilical artery blood flow and rapidly worsening laboratory indexes: A case report.
HELLP syndrome, a rare but serious obstetric complication, is often overdiagnosed due to its nonspecific symptoms and inappropriate clinical testing. A 30-year-old nulliparous pregnant Chinese woman at gestational age of 28+1 weeks was admitted to our hospital because Doppler ultrasonography at a local hospital had detected loss of fetal umbilical artery end-diastolic blood flow lasting 12 hours. On admission to our hospital, the patient showed elevated blood pressure (148/84 mm Hg), but blood pressure and laboratory indicators after admission were normal. However, the patient developed abdominal pain during hospitalization. Dexamethasone was given after admission to our hospital to promote fetal lung maturation, magnesium sulfate was given to protect fetal brain nerves, and maternal blood pressure was closely monitored. In addition, fetal umbilical artery blood flow was dynamically monitored. After three days in hospital with normal blood pressure, the patient developed abdominal pain accompanied by diarrhea. She was positive for Murphy's sign and laboratory tests showed no obvious abnormalities. Acute cholecystitis was suspected, but symptomatic and supportive treatment did not relieve abdominal pain and her blood pressure increased progressively to 212/130 mm Hg. Magnesium sulfate was given immediately to prevent spasm, and nitroglycerin was administered intravenously against hypertension. Liver enzymes, blood coagulation, and routine urinalysis were abnormal. The patient was diagnosed with HELLP syndrome, and an emergency cesarean section was performed. HELLP syndrome. After the cesarean section, platelet (PLT) count continuously decreased and transaminase and bilirubin levels continously increased. The newborn was transferred to the neonatal intensive care unit after birth and discharged at a corrected gestational age of 34 weeks. By postoperative day 6, laboratory indicators had returned to normal and the patient was discharged. Our case highlights that HELLP syndrome is a serious complication, and it should be diagnosed carefully and not arbitrarily on the basis of some abnormal indicators and stable clinical manifestations. Accurate early identification, active monitoring and management are essential for improving prognosis and avoiding maternal or infant mortality.


Viscerotropic Rocky Mountain spotted fever in southeastern Texas: report of a survivor with atypical manifestations and multiple organ failure.
A 32-year-old black man from rural southeastern Texas had headache, fever, chills, bronchopneumonia, and an atypical rash, complicated by hypotension, lethargy, confusion, liver dysfunction, thrombocytopenia, and acute renal failure. The diagnosis of Rocky Mountain spotted fever (RMSF) was not suspected until eight days after the onset of symptoms. He was subsequently treated with chloramphenicol, followed by hemodialysis and aggressive supportive therapy. He recovered uneventfully with complete return of renal function. This case emphasizes that RMSF should be considered in the differential diagnosis of any obscure febrile illness even in nonendemic areas.


Engineered porosity for tissue-integrating, bioresorbable lifetime-based phosphorescent oxygen sensors.
Versatile silk protein-based material formats were studied to demonstrate bioresorbable, implantable optical oxygen sensors that can integrate with the surrounding tissues. The ability to continuously monitor tissue oxygenation in vivo is desired for a range of medical applications. Silk was chosen as the matrix material due to its excellent biocompatibility, its unique chemistry that facilitates interactions with chromophores, and the potential to tune degradation time without altering chemical composition. A phosphorescent Pd (II) benzoporphyrin chromophore was incorporated to impart oxygen sensitivity. Organic solvent-based processing methods using 1,1,1,3,3,3-hexafluoro-2-propanol were used to fabricate: 1) silk-chromophore films with varied thickness and 2) silk-chromophore sponges with interconnected porosity. All compositions were biocompatible and exhibited photophysical properties with oxygen sensitivities (i.e., Stern-Volmer quenching rate constants of 2.7-3.2 × 104 M-1) useful for monitoring physiological tissue oxygen levels and for detecting deviations from normal behavior (e.g., hyperoxia). The potential to tune degradation time without significantly impacting photophysical properties was successfully demonstrated. Furthermore, the ability to consistently monitor tissue oxygenation in vivo was established via a multi-week rodent study. Histological assessments indicated successful tissue integration for the sponges, and this material format responded more quickly to various oxygen challenges than the film samples.


The value of the D-xylose test compared with the differential sugar absorption test in recognizing coeliac disease.
To compare the value of the differential sugar absorption test (SAT) with the blood and urine D-xylose tests (DXTs and DXTu) in diagnosing coeliac disease (CD) the SAT and the standard DXTs and DXTu were performed in 14 coeliacs with abnormal small bowel histology and in 12 patients with aspecific gastrointestinal complaints. In the SAT a solution of lactulose (L) and mannitol (M) was given to the fasting patient after which the L/M ratio was measured in 5 h urine by gas chromatography. In the DXTs and DXTu a solution of 25 g D-xylose was given to the fasting patient and blood was drawn at 0, 30 and 120 min and urine was collected for 5 h, respectively. To measure the power in diagnosing CD of the SAT, DXTs 30 min, DXTs 120 min and DXTu, the test results were plotted in ROC curves and the areas under the curves (AUCs) were calculated. The AUCs were 0.97, 0.77, 0.78 and 0.63, respectively. In our opinion, the DXTs and DXTu are no longer useful in the investigation of mucosal function of the small bowel.


2-[3-Hy-droxy-4-(2-hy-droxy-eth-oxy)phen-yl]-4,4,5,5-tetra-methyl-2-imidazoline-1-oxyl 3-oxide.
In the title compound, C(15)H(21)N(2)O(5), the imidazoline ring displays a twisted conformation. The mean plane of the imidazoline ring makes a dihedral angle of 22.55 (5)° with the benzene ring. In the crystal, O-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules into a layer parallel to the bc plane.


A systematic review and meta-analysis of the prevalence, trends, and geographical distribution of HIV among Chinese female sex workers (2000-2011): implications for preventing sexually transmitted HIV.
The aim of this meta-analysis was to investigate temporal and geographical trends in the HIV epidemic among female sex workers (FSWs) recruited from various venues in China. Chinese and English peer-reviewed articles published between January 2000 and February 2013 were systematically searched. Standard meta-analysis methods were used to calculate the pooled HIV prevalence, in accordance with the PRISMA guidelines. The national HIV prevalence among FSWs declined from 0.74% (95% confidence interval (CI) 0.37-1.49%) in 2000-2002 to 0.40% (95% CI 0.31-0.53%) in 2009-2011. All Chinese regions demonstrated significant declines in HIV prevalence, apart from the East and South Central regions, in which the epidemics stabilized at low/moderate levels. Despite a significant decline from 1.92% (95% CI 0.86-4.24%) to 0.87% (95% CI 0.65-1.18%) during 2000-2011, Southwest China still bore the greatest HIV disease burden. Nationwide, FSWs recruited from detention centres had the highest HIV prevalence (0.92%, 95% CI 0.46-1.88%), followed by voluntary counselling and testing sites (0.80%, 95% CI 0.46-1.67%) and entertainment venues (0.61%, 95% CI 0.47-0.79%). The prevalences among FSWs in high-, middle-, and low-tier entertainment venues were 0.59% (95% CI 0.32-1.45%), 0.92% (95% CI 0.50-1.77%), and 1.10% (95% CI 0.71-2.16%), respectively. High- and middle-tier FSWs had a significantly lower risk of HIV infection than lower-tier FSWs (high/low: odds ratio (OR) 0.48, 95% CI 0.40-0.59; middle/low: OR 0.49, 95% CI 0.37-0.66). The HIV epidemic has shown a gradual declining or stabilizing trend among Chinese FSWs. Intervention efforts should be diverted to high-risk subgroups of FSWs, such as drug-using and low-tier FSWs.


A microwave-assisted fluorescent labeling method for the separation and detection of amphetamine-like designer drugs by capillary electrophoresis.
A microwave-assisted fluorescence labeling method for use in CE-LIF (capillary electrophoresis-laser induced fluorescence) is described. Six amphetamine-like designer drugs, namely, o-, m-, p-chloro- and o-, m-, p-fluoro-amphetamine derivatives, were synthesized and used as model compounds. FITC (fluorescein isothiocyanate isomer I) and a blue-laser were used as the fluorescent labeling reagent and excitation source, respectively. When a microwave oven was used, the reaction was complete within ∼5 min, while the classical method required at least 20 h (usually, an overnight reaction). A mimic oral fluid sample was obtained by spiking oral fluid from a volunteer with the six standards, and after liquid-liquid extraction and microwave-derivatization, it was possible to process the analytes by CE-LIF within a period of ∼10 min; the wavelength of the blue-laser used was 473 nm. For comparison, data obtained using classical methods, including CZE-UV (capillary zone electrophoresis-UV absorbance detection), sweeping-MEKC-UV (micellar electrokinetic chromatography-UV absorbance detection) and LC-Q-TOFMS (liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry) are also reported.


The effects of juror anonymity on jury verdicts.
This study examined the effects of anonymity on jurors' verdicts and on jurors' feelings of accountability for their jury's verdicts. Twenty four-person anonymous juries and 20 four-person nonanonymous juries rendered individual and group verdicts for three student defendants charged with selling drugs on a school campus. When unanimous guilty verdicts were reached, juries imposed one of five punishments. Finally, jurors completed postdeliberation opinion and accountability questionnaires. As predicted, anonymous juries showed a higher rate of conviction (70%) than did nonanonymous juries (40%) when the evidence against the defendant was strong, supporting the hypothesis that anonymity would have a greater effect for situations in which there was relatively strong evidence of the defendant's guilt. Anonymous juries imposed the harshest punishment (expulsion) significantly more often than did nonanonymous juries. Contrary to predictions from differential self-awareness theory, anonymous juries did not report feeling less accountable than did nonanonymous juries. However, anonymous juries did see the process as significantly more fair than did identifiable juries.