Work limitations and productivity loss are associated with health-related quality of life but not with clinical severity in patients with psoriasis.
According to current guidelines the cost of productivity loss should be considered in pharmacoeconomic analyses. The cost of health-related productivity loss in psoriasis patients is unknown. To estimate the cost of productivity loss in psoriasis and its association with health-related quality of life and clinical disease severity. Cross-sectional study, recruitment of adult participants through Internet advertisements. 201 (72.3%) out of 278 eligible participants completed the study. Health-related work productivity loss, quality of life and clinical severity of psoriasis were assessed by standardized instruments. Indirect costs of productivity loss clearly exceed the total direct cost. In contrast to objective clinical disease severity, health-related quality of life (measured by the Dermatology Life Quality Index) is an independent predictor of work productivity. There is good reason to believe that intervention can reduce health-related productivity loss by improving patients' quality of life. Savings from increased work productivity might offset comparatively high acquisition costs of biological agents.


A simplified valve formula for the calculation of stenotic cardiac valve areas.
We have simplified the Gorlin formula and have compared our measurements of the aortic or mitral valve area, using the original Gorlin formula and the simplified valve formula in 100 consecutive patients. The valve area was measured by the simplified formula as cardiac output (l/min) divided by the square root of pressure differences across the valve. In patients with aortic stenosis of varying severity there were excellent correlation between the original Gorlin formula and the simplified formula (r = 0.96, y = 0.99x + 0.01, SEE = +/- 0.10, p less than 0.001). The correlation was unchanged when the peak gradient was used instead of the mean gradient in the simplified formula. Excellent correlation was also seen in patients with mitral stenosis of varying severity (r = 0.94, y = 0.97x - 0.02, SEE = +/- 0.19; p less than 0.001). The simplicity of the formula makes it easy to memorize and use.


Greater weight loss with increasing age in the weight loss maintenance trial.
To determine the effect of age on weight loss and weight loss maintenance in participants in the Weight Loss Maintenance trial (WLM). Secondary analysis of a randomized controlled trial of overweight/obese adults with CVD risk factors was conducted. Participants were 1685 adults with baseline BMI 25-45 kg m(2) with hypertension and/or dyslipidemia. Those who lost at least 4kg in an initial 6-month behavioral weight loss intervention (N = 1,032) were randomly assigned to a 30-month maintenance phase of self-directed control (SD), monthly personal counseling (PC), or unlimited access to an internet-based intervention (IT). Age groups were defined post-hoc and weight change was compared among age groups. Participants ≥60 years old initially lost more weight than younger individuals, and sustained greater weight loss in IT and PC but not in SD (P value for trend 0.024, 0.002, and 0.36, respectively). In WLM, adults age ≥60 years had greater initial weight loss and greater sustained weight loss over 3 years, compared to younger adults. Older adults had greater weight loss maintenance with either personal counseling or internet-based intervention. Future research should determine optimal implementation strategies and effects of weight loss on health outcomes in older adults.


Four new species of KudoaMeglitsch, 1947 (Myxosporea: Multivalvulida) from Australia with recommendations for species descriptions in the Kudoidae.
Kudoid parasites are significant pathogens of marine fish. In the past, specific identification has been difficult due to a paucity of detailed morphological and biological information provided in the original description of some species. However, the introduction of DNA analysis has dramatically improved diagnosis. For morphological characterization, this paper proposes a new set of schematics including additional measurements to give a more thorough description of spore morphology, and provides evidence for uniqueness of 4 new species: Kudoa gunterae n. sp. (from 10 pomacentrid species and 1 apogonid species), K. kenti n. sp. (from 4 pomacentrid species), K. paraquadricornis n. sp. (from 4 carangid species), and K. whippsi n. sp. (from 8 pomacentrid species and 1 apogonid species). Subtle morphological differences found between closely related species were reflected in their genetics, with increased resolution provided by the large subunit, compared with that of the small subunit, of the ribosomal DNA gene region. This article proposes comprehensive requirements for species descriptions within the Kudoidae that incorporate biology, morphology, and genetic sequence.


The sodium and chloride dependence of chloride secretion by the opercular epithelium.
The effects of ion substitutions on the Cl- secretion rate and tissue conductance of isolated short-circuited opercular epithelia from sea-water-adapted Fundulus heteroclitus were investigated. Serosal Na+ substitution had the same effect on the Cl- secretion rate that serosal Cl- substitution had on the active component of the Cl- efflux. This similarity indicated a 1:1 Na-Cl requirement for active Cl- secretion across this epithelium, which supports the proposal of a coupled NaCl uptake mechanism at the serosal membrane of Cl- secretory epithelia. Mucosal Na+ and Cl- substitutions appeared to inhibit completely the active Cl- secretory flux. The reductions in the tissue conductance with mucosal ion substitutions suggested that this effect can be attributed to a blocking of the apical membrane Cl- conductance. These mucosal ion effects suggested a possible direct regulatory influence of the external salinity on the Cl- secretion rate and tissue conductance, which provide alternative explanations for observations with the teleost gill epithelium.


Effects of driver cell-phone use on driver aggression.
Using 2 field procedures, the authors assessed impacts of cell-phone use on mild forms of driver aggression. Participants were 135 drivers traveling within a city of approximately 17,000 people in an otherwise little-populated region of western North Dakota. The authors videotaped the participants while a confederate driver in a low-status vehicle frustrated them. In Experiment 1, the confederate was traveling well under the posted speed limit. In Experiment 2, the confederate remained motionless at a stoplight that had turned green. When the confederate visibly talked on a hand-held cell phone (n = 67), male drivers exhibited their frustration by honking their horn more quickly and frequently than did drivers in no-cell-phone trials, and female drivers were more angry according to blind judgments of videotaped facial expressions that were compared with those of drivers in no-cell-phone trials (n = 68). The present results suggested that driver cell-phone use contributes to the growing crisis of roadway aggression.


Development of spontaneous motility in chick embryos. Further components of aminergic mechanisms.
The participation of central monoaminergic systems in the regulation of spontaneous motility in developing chick embryos was tested by systemic administration of several drugs, which affect the different sites of central aminergic systems. Amphetamine (2 mg.kg-1 egg weight) evoked an age-dependent depression of spontaneous motility, which first occurred in a significant fashion on day 13 of incubation. Two thirds of this depression depended upon supraspinal influences. The effect of p-chlorophenylalanine (100 mg.kg-1 e.w.) consisted from day 15 of incubation in a short-lasting depression followed by partial recovery of resting motility. alpha-methyldopa (100 mg.kg-1 e.w.) depressed the spontaneous motility from day 13 of incubation, without any signs of recovery within the first hour after drug administration. The most pronounced depressive effect was evoked by melatonin (25 mg.kg-1 e.w.) even in 11-day-old embryos. Along with the increased depth of depression the recovery of motility declined until full cessation of motility was achieved in 17-day-old embryos. The results were interpreted as constituting further evidence for the involvement of central aminergic systems in the development of supraspinal control over spontaneous motor activity generated by the CNS.


Roll-over shapes of the ankle-foot and knee-ankle-foot systems of able-bodied children.
The roll-over shape is the effective rocker shape that a lower limb system conforms to during a step. The roll-over shape concept has been explored in detail in adults and has been successfully used in the design, evaluation, and alignment of lower limb prostheses and orthoses. No such analysis exists for the pediatric population. Therefore, the purpose of this study was to investigate the ankle-foot and knee-ankle-foot roll-over shapes in able-bodied children, values that could serve as tools for design and evaluation of lower limb pediatric prostheses and orthoses. This study describes a multi-center retrospective review of existing motion analysis data (n=153 from three centers). Roll-over shapes were calculated by transforming center of pressure data from a laboratory-based coordinate system into two body-based coordinate systems. Roll-over shapes were then characterized using a circular arc model. Best-fit radii of roll-over shapes for children in three age groups (3-7 years, 8-11 years, and 12-17 years) were compared using the Kruskal-Wallis test. No significant changes were found in roll-over shape radii between the three age groups (P=0.54 for ankle-foot roll-over shape radii; P=0.12 for knee-ankle-foot roll-over shape radii). The weighted mean of median radii for ankle-foot and knee-ankle-foot roll-over shapes from the three centers were approximately 22% and 17% of body stature, values similar to those seen in adults. Children produce nearly circular knee-ankle-foot roll-over shapes at a young age that are similar to those seen in adults when scaled by body stature.


Coarctation and hypoplasia of the aortic arch: will the arch grow?
Hypoplasia of the transverse aortic arch of various degrees of severity is commonly seen in infants who have coarctation of the aorta. It is more often present when the coarctation is associated with intracardiac lesions that diminish or limit forward flow in the ascending aorta and promote right to left flow through an arterial duct. The increased frequency of surgical treatment of infants with complex coarctation, which is in part related to the ability to stabilize their condition with prostaglandin E1, has posed the question of the potential for growth and development of the originally hypoplastic aortic arch after conventional repair of aortic coarctation. Review of our experience with transverse aortic arch hypoplasia, found in 33 (32%) of 102 infants undergoing coarctation repair by subclavian flap aortoplasty or classic resection and end-to-end anastomosis, revealed excellent growth of the transverse arch after repair in all patients available for linear follow-up. The currently proposed extended arch repair should be reserved for the small group of infants with transverse aortic arch to ascending aorta diameter ratios (arch indices) of less than 0.25.


Toxicological profile of IQG-607 after single and repeated oral administration in minipigs: An essential step towards phase I clinical trial.
IQG-607 is an anti-tuberculosis drug candidate, with a promising safety and efficacy profile in models of tuberculosis infection both in vitro and in vivo. Here, we evaluated the safety and the possible toxic effects of IQG-607 after acute and 90-day repeated administrations in minipigs. Single oral administration of IQG-607 (220 mg/kg) to female and male minipigs did not result in any morbidity or mortality. No gross lesions were observed in the minipigs at necropsy. Repeated administration of IQG 607 (65, 30, or 15 mg/kg), given orally, for 90 days, in both male and female animals did not cause any mortality and no significant body mass alteration. Diarrhea and alopecia were the clinical signs observed in animals dosed with IQG-607 for 90 days. Long-term treatment with IQG-607 did not induce evident alterations of blood cell counts or any hematological parameters. Importantly, the repeated schedule of administration of IQG-607 resulted in increased cholesterol levels, increased glucose levels, decrease in the globulin levels, and increased creatinine levels over the time. Most necropsy and histopathological alterations of the organs from IQG-607-treated groups were also observed for the untreated group. In addition, pharmacokinetic parameters were evaluated. IQG-607 represents a potential candidate molecule for anti-tuberculosis drug development programs. Its promising in vivo activity and mild to moderate toxic events detected in this study suggest that IQG-607 represents a candidate for clinical development.


RNA-Free and Ribonucleoprotein-Associated Influenza Virus Polymerases Directly Bind the Serine-5-Phosphorylated Carboxyl-Terminal Domain of Host RNA Polymerase II.
Influenza viruses subvert the transcriptional machinery of their hosts to synthesize their own viral mRNA. Ongoing transcription by cellular RNA polymerase II (Pol II) is required for viral mRNA synthesis. By a process known as cap snatching, the virus steals short 5' capped RNA fragments from host capped RNAs and uses them to prime viral transcription. An interaction between the influenza A virus RNA polymerase and the C-terminal domain (CTD) of the large subunit of Pol II has been established, but the molecular details of this interaction remain unknown. We show here that the influenza virus ribonucleoprotein (vRNP) complex binds to the CTD of transcriptionally engaged Pol II. Furthermore, we provide evidence that the viral polymerase binds directly to the serine-5-phosphorylated form of the Pol II CTD, both in the presence and in the absence of viral RNA, and show that this interaction is conserved in evolutionarily distant influenza viruses. We propose a model in which direct binding of the viral RNA polymerase in the context of vRNPs to Pol II early in infection facilitates cap snatching, while we suggest that binding of free viral polymerase to Pol II late in infection may trigger Pol II degradation. Influenza viruses cause yearly epidemics and occasional pandemics that pose a threat to human health, as well as represent a large economic burden to health care systems globally. Existing vaccines are not always effective, as they may not exactly match the circulating viruses. Furthermore, there are a limited number of antivirals available, and development of resistance to these is a concern. New measures to combat influenza are needed, but before they can be developed, it is necessary to better understand the molecular interactions between influenza viruses and their host cells. By providing further insights into the molecular details of how influenza viruses hijack the host transcriptional machinery, we aim to uncover novel targets for the development of antivirals.


A longitudinal study examining the independence of apathy and depression after stroke: the Sydney Stroke Study.
There is growing recognition that apathy is not only a symptom of depression but may be an independent syndrome. This is the first study to investigate the relationship of apathy and depression longitudinally following stroke and to examine the association with dementia. 106 consecutive eligible participants following stroke received extensive medical, psychiatric and neuropsychological assessments at three to six months (index assessment) and 15 months (follow-up assessment) after their stroke. A subset of participants received magnetic resonance imaging (MRI) scans at index assessment. Ratings were made for DSM-IV major or minor depression and for apathy using the Apathy Evaluation Scale (AES). While there was no significant overlap between apathy and depression at index assessment (OR = 1.79, 95% CI 0.48, 6.66), the overlap was significant a year later (OR = 7.75, 95% CI 2.60, 23.13). Dementia at index assessment was a common risk factor for both apathy and depression at follow-up (OR = 12.45, 95% CI 2.98, 52.02 and OR = 10.35, 95% CI 2.84, 37.72, respectively). Apathy and depression after stroke have a common predictor and overlap longitudinally. The overlap might be due to cumulative vascular pathology and because of the relationship of each of these syndromes to dementia, which was an important, possibly causal, predictor for both.


[The parent-child bond tested by a placement].
When a child is placed by a legal ruling into institutional care, his or her parents have correspondence, visiting and accommodation rights. The child welfare judge fixes the terms and can, if it is deemed to be in the child's interest, suspend the arrangement. He or she can also order that any visits are carried out in the presence of a third party nominated by the institution or the service to which the child has been entrusted.


Commercial determinants of health: an ethical exploration.
This paper seeks to contribute toward a better understanding of commercial determinants of health by proposing a set of ethical principles that can be used by researchers and other health actors in understanding and addressing Commercial Determinants of Health (CDoH). The paper is mainly based on a systematic review and qualitative analysis of the existing literature on CDoH and public health ethics frameworks. We conducted searches using selected search engines (Google Scholar and Pubmed). For ethical challenges relating to CDOH, our searches in Google Scholar yielded 17 papers that discussed ethical challenges that affect CDoH. For ethical frameworks relevant for CDOH, our searches in Google Scholar and Pubmed yielded 15 papers that clearly described bioethical models including relevant ethical principles. Additionally, we consulted eight experts working on CDoH. Through these two methods, we were able to identify ethical challenges as well as norms and values related to CDoH that we offer as candidates to comprise a foundational ethics framework for CDoH. Discussing risk factors associated with CDH frequently brings public health into conflict with the interests of industry actors in the food, automobile, beverage, alcohol, ammunition, gaming and tobacco industries including conflict between profit-making and public health. We propose the following candidate ethical principles that can be used in addressing CDoH: moral responsibility, nonmaleficence, social justice and equity, consumer sovereignty, evidence-informed actions, responsiveness, accountability, appropriateness, transparency, beneficence and holism. We hope that this set of guiding principles will generate wider global debate on CDoH and help inform ethical analyses of corporate actions that contribute to ill health and policies aimed at addressing CDoH. These candidate principles can guide researchers and health actors including corporations in addressing CDoH.


Ace inhibitor therapy for heart failure in patients with impaired renal function: a review of the literature.
Heart failure syndromes are often associated with multi-organ dysfunction, and concomitant liver, renal, and neurologic involvement is very common. Neuro-hormonal antagonism plays a key role in the management of this syndrome, and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are one of the cornerstones of therapy. Cardiorenal physiology is becoming more recognized in these patients with advanced heart failure, and the role of neuro-hormonal blockade in this setting is vaguely defined in the literature. Often, angiotensin-converting enzyme inhibitors are decreased or even withheld in these circumstances. The purpose of this article is to review the role and pathophysiology of ace inhibition and angiotensin receptor blockade in patients with acute and chronic heart failure syndromes and concomitant cardiorenal physiology.


From apes to humans: locomotion as a key feature for phylogeny.
If bipedalism has often been considered to be of a crucial interest for understanding hominid evolution, the acceptance of locomotor features to build phylogenies is still far from being a reality in the field. Especially for hominid evolution, it still seems to be difficult to accept that traits, other than craniodental ones, can be useful for defining the major dichotomies. The recent discovery of Australopithecus anamensis suggests a challenging view of the major dichotomy between apes and humans. Whilst it is widely accepted that Ardipithecus ramidus is ancestral to Australopithecus anamensis, which in its turn is ancestral to Australopithecus afarensis and then to later hominids, the postcranial adaptations, which should be taken into account, suggest another branching pattern. Based on the fact that by 4.0 million years two different locomotor patterns can be identified in hominids, two lineages would appear to be present: the "Australopithecine" lineage (with Australopithecus afarensis or Ardipithecus ramidus if the latter is really a hominid sensu stricto) and the "Hominine" lineage (with Australopithecus anamensis = Praeanthropus africanus).


Ethanol-induced teratogenesis: free radical damage as a possible mechanism.
To investigate the possibility of a free radical mechanism for ethanol-induced teratogenesis, gestational day 8 mouse embryos were exposed for 6 hr in whole embryo culture to a teratogenic dosage of ethanol alone (500 mg%) or in conjunction with an antioxidant, superoxide dismutase (SOD; 300 U/ml). For subsequent analysis, some embryos were examined at the end of this 6-hr period, while others were removed to control medium and cultured for an additional time period. Ethanol exposure resulted in increased superoxide anion generation and increased lipid peroxidation (as noted 6 hr after initial ethanol exposure) and in excessive cell death (as noted 12 hr after initial exposure) in the embryos. Following a total of 36 hr in culture, a high incidence of malformation, including failure of the anterior neural tube to close in 63% of the ethanol-exposed embryos, was noted. The ethanol-induced superoxide anion generation, lipid peroxidation, excessive cell death, and dysmorphogenesis were diminished in embryos co-treated with SOD, suggesting that the teratogenicity of ethanol is mediated, at least in part, by free radical damage.


ICD-11 Morbidity Pilot in Kuwait: Methodology and Lessons Learned for Future Implementation.
This paper reports on the first ICD-11 morbidity pilot for inpatient discharges in a public general hospital. We detail the pilot methodology, lessons learned in terms of facilitators and challenges, physician-reported opinion, and considerations for future implementation. The pilot included: engaging stakeholders; selecting the setting; building a common understanding of the discharge process; evaluating and preparing IT infrastructure; ICD-11 training; small-scale pre-pilot testing; implementing the pilot while providing on-site support and collecting data for analysis including a brief user-experience survey. Overall, physicians were satisfied with the experience. Facilitators for success included national health system influence, leadership commitment, a multidisciplinary team approach, physician-tailored training, using social media for training, and providing on-site support. Challenges included potential IT problems, and difficulties relating to training and engaging physicians. Issues to consider include DRG system requirements, and comparability of ICD-11 pilot results from different countries. In conclusion, ICD-11 can be successfully implemented for documenting diagnoses by physicians in a public hospital by installing the coding tool on the electronic hospital information system. Pilots can improve ICD-11 content by using the online proposal mechanism. Implementing ICD-11 requires effective change management, stakeholder-tailored communication, and innovative ideas for training to match the electronic nature of ICD-11 and its potential new users, physicians.


Localization of enzymes of ureide biosynthesis in peroxisomes and microsomes of nodules.
The intracellular location of enzymes involved in the synthesis of the ureides, allantoin and allantoic acid, was investigated in nodules of Glycine max L. Merr. Cellular organelles were separated on isopycnic sucrose density gradients. Xanthine dehydrogenase activity (270 nanomoles per min per gram fresh weight) was totally soluble, whereas approximately 15% of the total uricase and catalase activities (1 and 2000 micromoles per minute per gram fresh weight, respectively) was in the fraction containing intact peroxisomes. Allantoinase activity (680 nanomoles per minute per gram fresh weight) was associated with the microsomal fraction, which apparently originates from the endoplasmic reticulum.


Synergistic childhood adversities and complex adult psychopathology.
Numerous studies find a cumulative effect of different types of childhood adversities on increasing risk for serious adult mental and medical outcomes. This study uses the National Comorbidity Survey-Replication sample to investigate the cumulative impact of 8 childhood adversities on complex adult psychopathology as indexed by (a) number of lifetime diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV; American Psychiatric Association, 1994); (b) number of 4 DSM-IV disorder categories (mood, anxiety, impulse control, and substance abuse disorders); and (c) coexistence of internalizing and externalizing disorders. Seven of the 8 childhood adversities were significantly associated with complex adult psychopathology. Individuals with 4 or more childhood adversities had an odds ratio of 7.3, 95% confidence interval [4.7, 11.7] for 4 disorder categories. Additive and multiplicative synergistic effects increasing adult psychopathology were found for specific pairwise combinations of childhood adversities. Synergistic patterns differed by gender suggesting that women are more impacted by sexual abuse and men by economic hardship. The absence of childhood adversities was protective, in that it significantly decreased an individual's risk for subsequent adult mental illness. The results support the clinical impression that increased childhood adversity is associated with more complex adult psychopathology.


Multidisciplinary discovery of ancient restoration using a rare mud carapace on a mummified individual from late New Kingdom Egypt.
CT scans of an unnamed mummified adult from Egypt, now in the Chau Chak Wing Museum, University of Sydney (NMR.27.3), reveal it to be fully sheathed in a mud shell or carapace, exposing a mortuary treatment not previously documented in the Egyptian archaeological record. The carapace was placed between layers of linen wrappings thus it was not externally visible. Radiocarbon dating of textile samples provide a range of c.1370-1113 cal BC (95.4% probability), with a median date of 1207 cal BC. When assessed against mummification techniques of the era, the individual is placed in the late 19th-20th Dynasty, at the later end of this date range. Multi-proxy analysis including μ-XRF and Raman spectroscopy of carapace fragments from the head area revealed it to consist of three layers, comprising a thin base layer of mud, coated with a white calcite-based pigment and a red-painted surface of mixed composition. Whether the whole surface of the carapace was painted red is unknown. The carapace was a form of ancient conservation applied subsequent to post-mortem damage to the body, intended to reconfigure the body and enable continued existence of the deceased in the afterlife. The carapace can also be interpreted as a form of elite emulation imitating resin shells found within the wrappings of royal bodies from this period.


The clinical expression of allergy in the skin.
The cutaneous immune system has evolved to protect the organism from potential exogenous pathogens in a complex manner. Recent investigations of the special role of the skin in allergy have focused on the proinflammatory potential of various cells such as Langerhans' cells, keratinocytes, mast cells (MC), endothelial cells, and dermal fibroblasts. Furthermore, in processing and reacting to antigens, infiltrating inflammatory cells (lymphocytes; monocytes; macrophages; and eosinophil, neutrophil, and basophil granulocytes) play an important role both by cell-cell interactions with specific receptors on cell surfaces and via soluble mediators.


Different growth factor requirements for the ex vivo amplification of transplantable human cord blood cells in a NOD/SCID mouse model.
The growth factor combination containing early acting cytokines FLT-3 ligand (FL), Stem Cell Factor (SCF) and thrombopoietin (TPO) is able to maintain, for an extended culture period, early stem cells, defined as long-term repopulating NOD/SCID mice (Scid Repopulating Cell-SRC) contained in cord blood (CB). In this culture system, the role of IL-6 and IL-3 has not been clearly established. Using a combination of FL+TPO+SCF with or without IL-6, we were able to form CB CD34+ cells for 30 weeks. The CB CD34+ cells cultured in this system engrafted NOD/SCID mice after 6 weeks of culture; the cells from primary recipients were also able to engraft secondary NOD/SCID mice. When CB CD34+ cells were cultured in the presence of IL-3 in the place of IL-6 we observed an even better expansion of cells and a similar clonogenic progenitor output in the first 8 weeks of culture. However, more primitive LTC-IC output increased up to week 6 with the growth factor combination containing IL-3 and then decreased and disappeared, while with the growth factor combination with or without IL-6 increased up to week 23. Cells cultured for 4 weeks with the 4-factor combination containing IL-3 engrafted NOD/SCID mice less efficiently. Repopulation of NOD/SCID mice was no longer observed when ex vivo expansion was performed for 6 weeks. This study provides some evidence that no differences could be detected in long-term maintenance and even expansion of human primitive cord blood cells cultured with FL+TPO+SCF in the presence or absence of IL-6. Under the culture conditions employed in this study, the presence of IL-3 reduced the repopulating potential of expanded CB CD34+ cells.


Clinical and Radiological Analysis of Pyogenic Vertebral Osteomyelitis Immediately after Successful Antimicrobial Therapy: Considerations for Assessing Therapeutic Response.
The clinical and radiological abnormal findings continue even after successful treatment in pyogenic vertebral osteomyelitis (PVO). We analyzed the clinical and radiological features of cured PVO based on 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (FDG-PET/MRI) and compared the radiological differences between FDG-PET and MRI for assessing therapeutic response in PVO. This study included 43 patients (28 men and 15 women) with lumbar PVO who had no recurrence after successful antimicrobial therapy. They were divided into two groups based on the location of maximum standardized FDG uptake value (SUVmax) of PVO lesion on FDG-PET/MRI when parenteral antibiotics were discontinued (31 in group A: Intervertebral structure; 12 in group B: Vertebral body and paravertebral muscle). The differences of clinical symptoms, hematological inflammatory indices, and radiological features were retrospectively analyzed. The patients were treated with 42.28 ± 14.58 (21-89) days of parenteral antibiotics. There were significant differences in C-reactive protein (0.97 ± 1.10 vs. 0.51 ± 0.31 mg/dL, p = 0.041; normal range of CRP < 0.5), back pain (4.29 ± 1.13 vs. 3.50 ± 1.00, p = 0.040; visual analog scale), and SUVmax (4.34 ± 1.24 vs. 5.89 ± 1.57, p < 0.001) between the two groups. In the distribution pattern of PVO lesions, FDG-PET overall showed recovery pattern earlier than MRI did (p < 0.001). In cured PVO, the clinical features vary depending on the location of major structural damage of PVO lesion. The involvement of intervertebral structure is related with sustained back pain and elevation of CRP, and vertebral body/paravertebral muscle shows favorable clinical features despite advanced structural damages.


Extracellular phosphate as a signaling molecule.
Phosphorus is involved in various biological processes including membrane integrity, maintenance and inheritance of genetic materials, energy metabolism, intracellular signaling and skeletal mineralization. In addition, accumulating evidences have indicated that alteration in the levels of extracellular inorganic phosphate (Pi) itself triggers signaling to regulate gene expression and cellular functions in some cell types. In bone cells such as osteoblasts and chondrocytes, extracellular Pi modulates cell proliferation, differentiation, mineralization and apoptosis. In extraskeletal tissues, extracellular Pi also exerts various effects. For example, increased extracellular Pi results in the calcification associated with the upregulation of osteoblast marker genes in vascular smooth muscle cells. As to the mechanistic aspects, it is suggested that an increase in extracellular Pi triggers signal transduction via the PiT1 type III sodium/phosphate (Na(+)/Pi) cotransporter and ERK1/2 pathway. Unicellular organisms such as bacteria and yeast sense the environmental Pi with a protein complex located in the plasma membrane, which regulates the expression of multiple genes involved in Pi uptake and metabolism to adapt to its availability. In mammals that are multicellular organisms, Pi availability should be sensed both at a cellular level to regulate the function of each cell and as a whole body to maintain the Pi homeostasis of the extracellular fluid. Although the responsiveness to the increased extracellular Pi suggests the existence of Pi-sensing mechanism in mammalian cells as well, it is unknown whether the sensing of Pi availability at a cellular level and that at a whole-body level share the same pathway or not. This chapter will review the findings regarding the regulation of various cellular functions by extracellular Pi, and also discuss the current concept on the mechanism for Pi-sensing.


Clinical profile, treatment and survival outcome of testicular tumors: a pakistani perspective.
Testicular cancer management is considered a marvel of modern science with excellent treatment results. Pakistan has a distinct ethnic variation and geographic distribution but data regarding clinical presentation of testicular tumors and their management is under reported. The objective of this study was to determine clinical profile, treatment modalities and survival outcome of testicular tumors in the Pakistani population. A retrospective review of patients who received treatment for testicular cancer at Shaukat Khanum Cancer Hospital from January 2009 to December 2012 was performed. Patient demographics, clinical features at presentation and treatment modalities were assessed. For categorical variables chi square test was used. Survival was calculated using Kaplan Meier survival curves and Log rank test was employed to determine significance. The most common tumor was mixed germ cell tumor in 49% patients. For all tumor variants except seminoma, stage III was the most common clinical stage at presentation. Majority of patients with non seminomatous germ cell tumors presented in the15-30 year age group as compared to seminoma which was most prevalent in the 30-40 year age group. Orchiectomy followed by chemotherapy was the most common treatment modality in 80% patients. Expected 5 year survival for seminomas and non- seminomatous germ cell tumors was 96% and 90% respectively which was not significantly different (p=0.2). Despite a distinct clinical profile of testicular tumors in Pakistani population, survival is comparable with published reports.


GABA visualized by immunocytochemistry in the guinea pig cochlea in axons and endings of efferent neurons.
Antiserum raised against GABA coupled with glutaraldehyde to bovine serum albumin was applied to the guinea pig cochlea. Immunoreactivity was visualized as horseradish peroxidase reaction product in surface preparations of the organ of Corti using immunocytochemical techniques. Bright-field, differential interference contrast and video-enhanced contrast light microscopy were used. GABA-like immunoreactivity was found in axons and endings of efferent neurons in all turns of the cochlear spiral, but predominantly in the third turn and first half of the fourth turn. In these apical turns, immunoreactivity was seen in the efferent components: inner spiral bundle, tunnel spiral bundle, tunnel-crossing fibers, large nerve endings synapsing on outer hair cell bases, nerve endings high up on outer hair cells, nerve endings or varicosities close to outer hair cells, and outer spiral fibers. Some immunoreactive large nerve endings at outer hair cells were found in the apical half of the fourth turn. This study shows that axons and endings of efferent neurons in the organ of Corti of guinea pig contain GABA-like immunoreactivity with a distribution similar to that of GAD-like immunoreactivity as shown in a previous study. In both studies, many efferent nerve axons and endings were unstained, even in regions of maximal density of immunoreactivity in the apical turns. The evidence indicates that a subpopulation of efferent neurons projecting to the organ of Corti is GABAergic and very likely different from the lateral and the medial olivocochlear efferent systems.


Functional circuit mapping of striatal output nuclei using simultaneous deep brain stimulation and fMRI.
The substantia nigra pars reticulata (SNr) and external globus pallidus (GPe) constitute the two major output targets of the rodent striatum. Both the SNr and GPe converge upon thalamic relay nuclei (directly or indirectly, respectively), and are traditionally modeled as functionally antagonistic relay inputs. However, recent anatomical and functional studies have identified unanticipated circuit connectivity in both the SNr and GPe, demonstrating their potential as far more than relay nuclei. In the present study, we employed simultaneous deep brain stimulation and functional magnetic resonance imaging (DBS-fMRI) with cerebral blood volume (CBV) measurements to functionally and unbiasedly map the circuit- and network level connectivity of the SNr and GPe. Sprague-Dawley rats were implanted with a custom-made MR-compatible stimulating electrode in the right SNr (n=6) or GPe (n=7). SNr- and GPe-DBS, conducted across a wide range of stimulation frequencies, revealed a number of surprising evoked responses, including unexpected CBV decreases within the striatum during DBS at either target, as well as GPe-DBS-evoked positive modulation of frontal cortex. Functional connectivity MRI revealed global modulation of neural networks during DBS at either target, sensitive to stimulation frequency and readily reversed following cessation of stimulation. This work thus contributes to a growing literature demonstrating extensive and unanticipated functional connectivity among basal ganglia nuclei.


(2E,5E)-2,5-Bis(4-hy-droxy-3-meth-oxy-benzyl-idene)cyclo-penta-none ethanol monosolvate.
In the title structure, C21H20O5·C2H5OH, the curcumine-type mol-ecule has a double E conformation for the two benzyl-idene double bonds [C=C = 1.342 (4) and 1.349 (4) Å] and is nearly planar with respect to the non-H atoms (r.m.s. deviation from planarity = 0.069 Å). The two phenolic OH groups form bifurcated hydrogen bonds with intra-molecular branches to adjacent meth-oxy O atoms and inter-molecular branches to either a neighbouring mol-ecule or an ethanol solvent mol-ecule. The ethanol O atom donates a hydrogen bond to the keto O atom. These hydrogen bonds link the constituents into layers parallel to (101) in the crystal structure.


Charge Separating Microfiltration Membrane with pH-Dependent Selectivity.
Membrane filters are designed for selective separation of components from a mixture. While separation by size might be the most common approach, other characteristics like charge can also be used for separation as presented in this study. Here, a polyether sulfone membrane was modified to create a zwitterionic surface. Depending on the pH value of the surrounding solution the membrane surface will be either negatively or positively charged. Thus, the charged state can be easily adjusted even by small changes of the pH value of the solution. Charged polystyrene beads were used as model reagent to investigate the pH dependent selectivity of the membrane. It was found that electrostatic forces are dominating the interactions between polystyrene beads and membrane surface during the filtration. This enables a complete control of the membrane's selectivity according to the electrostatic interactions. Furthermore, differently charged beads marked with fluorescent dyes were used to investigate the selectivity of mixtures of charged components. These different components were successfully separated according to their charged state proving the selectivity of the invented membrane.


Activated lymphocytes induce promoter activity of the TCA3 gene in mast cells following cell-to-cell contact.
Aggregates of mast cells and lymphocytes have been found in inflamed tissues suggesting that lymphocytes may have the ability to activate mast cells through cell-to-cell contact. To examine this hypothesis, murine mast cells were transfected with a T cell activation gene-3 (TCA3)-chloramphenicol acetyl transferase (CAT) construct, and these cells co-cultured with murine EL-4 (T), CH12.LX (B), WEHI-3 (myelomonocytic) or 3T3(fibroblast) cell lines. Co-culture of activated EL-4 or CH12.LX cells, but not WEHI-3 or 3T3 cells, with transfected mast cells induced a 5 to 7 fold increase in CAT expression which was dependent on the lymphocyte to mast cell ratio. Supernatants from activated EL-4 or CH12.LX cells did not induce CAT expression in transfected mast cells. These data demonstrate that activated lymphocytes have the ability to induce the promoter of the TCA3 gene in mast cells through a mechanism requiring cell-to-cell contact, and suggest the possibility that activated lymphocytes may effect other biologic processes in mast cells as well through such heterotypic activation.


Synergistic action of Flt3 and gp130 signalings in human hematopoiesis.
We recently showed that c-kit signal synergizes with glycoprotein (gp)130 signal mediated by a complex of interleukin (IL)-6 and soluble IL-6 receptor (IL-6/sIL-6R) to stimulate the expansion of human primitive hematopoietic progenitor cells and erythropoietin-independent erythropoiesis. In the present study, we examined the effect of a ligand for Flt3 (FL), whose receptor tyrosine kinase is closely related to c-kit, in combination with IL-6/sIL-6R on human hematopoiesis in vitro. In serum-containing methylcellulose clonal culture of cord blood CD34(+) cells, whereas FL alone stimulated only granulocyte-macrophage (GM) colony formation, erythroid bursts and mixed colonies in addition to GM colonies were induced by FL with IL-6/sIL-6R, but not IL-6/sIL-6R alone. In suspension culture, CD34(+) cells generated a small number of myeloid cells in the presence of FL or IL-6/sIL-6R alone. However, the addition of IL-6/sIL-6R to the culture with FL induced the generation of a significant number of erythroid cells and megakaryocytes in addition to myeloid cells. The combination of FL and IL-6/sIL-6R also induced a remarkable expansion of GM colony- and erythroid burst-forming cells and multipotential progenitors, although FL or IL-6/sIL-6R alone induced the generation of only a small number of progenitors for GM colonies. The synergistic effects of FL and IL-6/sIL-6R were confirmed in serum-free clonal and suspension cultures. In addition, the addition of anti-human gp130 monoclonal antibodies abrogated the synergistic action. These results indicate that Flt3 signal, as well as c-kit signal, synergizes with gp130 signal to stimulate human myelopoiesis, erythropoiesis and megakaryopoiesis, and the expansion of primitive multipotential hematopoietic progenitor cells.


[Combination intestinal lavage: a conservative procedure for colonoscopy].
The purpose of this study was to optimize the cleaning for colonoscopy. We compared a combination of senna pods and Goleytely solution to the exclusive ingestion of 7 litres of Goleytely solution. Test parameters were the score of visual assessment in five regions of the large bowel, the distension of the abdomen, concentration of hydrogen and methane in intestinal gases and subjective informations about abdominal complaints. We concluded from 80 colonoscopies that the combined procedure was almost identical with the cleaning by voluminal ingestions of Goleytely solution. There were no differences in the scores of visual assessment or concerning the intestinal gases. The additional administration of simethicone resulted in a statistically significant decrease of foam production. Thus, the combination of senna pods, a reduced ingestion of Goleytely solution supplemented with simethicone can be recommended for colonoscopy.


Encystation of entamoeba parasites.
Entamoeba histolytica is a protozoan parasite of humans, and the causitive agent of intestinal amebiasis. The disease-causing stage of the parasite is an osmotically sensitive ameboid form, which differentiates into a thick-walled cyst for transmission from person to person. The conditions within the human intestine that induce encystment of the amoeba are unknown, but studies using an amoebic parasite of reptiles are now yielding information about the molecules and host:parasite interactions involved in the process. An understanding of the amoeba's obligatory encystment pathway should provide an approach for interrupting the transmission of this parasite, for which there is currently no vaccine.


Morphology-controllable synthesis and characterization of hierarchical 3D Co1-xMnxO nanostructures.
Multirod and hierarchically spherical 3D Co(1-x)Mn(x)O (2/3 < or = x < or = 1) nanostructures have been successfully synthesized by the decomposition of acetylacetonate precursors. Their morphologies could be controlled through tuning the heat rating which affects the nucleation. The rods grew along [110] directions to reduce the appearance of high-energy crystallographic {110} planes. The hierarchically spherical superstructures were formed by a three-dimensional oriented-attachment mechanism. Magnetic measurement indicates that the MnO nanomaterials with hierarchically spherical superstructures show an antiferromagnetic transition temperature at 121 K, similar to that of bulk, and a ferromagnetic ordering exists at low temperature. Such anomalous magnetic properties arise plausibly from their microstructure characteristics.


Palladium-catalyzed direct (hetero)arylation of ethyl oxazole-4-carboxylate: an efficient access to (hetero)aryloxazoles.
A straightforward route toward 2-(hetero)arylated and 2,5-di(hetero)arylated oxazoles through regiocontrolled palladium-catalyzed direct (hetero)arylation of ethyl oxazole-4-carboxylate with iodo-, bromo-, and chloro(hetero)aromatics followed by a two-step hydrolysis/decarboxylation sequence was described. The method was applied here to a neat synthesis of two 2,5-di(hetero)aryloxazole natural products, balsoxin and texaline.


Prognostic Value of Right Ventricular Ejection Fraction Assessed by 3D Echocardiography in COVID-19 Patients.
Background: RVEF (right ventricular ejection fraction) measured by three-dimensional echocardiography (3DE) has been used in evaluating right ventricular (RV) function and can provide useful prognostic information in other various cardiovascular diseases. However, the prognostic value of 3D-RVEF in coronavirus disease 2019 (COVID-19) remains unknown. We aimed to investigate whether 3D-RVEF can predict the mortality of COVID-19 patients. Methods: A cohort of 128 COVID-19-confirmed patients who had undergone echocardiography were studied. Thirty-one healthy volunteers were also enrolled as controls. COVID-19 patients were divided into three subgroups (general, severe, and critical) according to COVID-19 severity-of-illness. Conventional RV structure and function parameters, RV free wall longitudinal strain (FWLS) and 3D-RVEF were acquired. RVFWLS was measured by two-dimensional speckle tracking echocardiography. RVEF was acquired by 3DE. Results: Compared with controls, 2D-RVFWLS and 3D-RVEF were both significantly decreased in COVID-19 patients (-27.2 ± 4.4% vs. -22.9 ± 4.8%, P < 0.001; 53.7 ± 4.5% vs. 48.5 ± 5.8%, P < 0.001). Critical patients were more likely to have a higher incidence of acute cardiac injury and acute respiratory distress syndrome (ARDS), and worse prognosis than general and severe patients. The critical patients exhibited larger right-heart chambers, worse RV fractional area change (RVFAC), 2D-RVFWLS, and 3D-RVEF and higher proportion of pulmonary hypertension than general and severe patients. Eighteen patients died during a median follow-up of 91 days. The multivariate Cox regression analysis revealed the acute cardiac injury, ARDS, RVFAC, RVFWLS, and 3D-RVEF were independent predictors of death. 3D-RVEF (chi-square to improve 18.3; P < 0.001), RVFAC (chi-square to improve 4.5; P = 0.034) and 2D-RVFWLS (chi-square to improve 5.1; P = 0.024) all provided additional prognostic value of higher mortality over clinical risk factors. Moreover, the incremental predictive value of 3D-RVEF was significantly (P < 0.05) higher than RVFAC and RVFWLS. Conclusion: 3D-RVEF was the most robust independent predictor of mortality in COVID-19 patients and provided a higher predictive value over conventional RV function parameters and RVFWLS, which may be helpful to identify COVID-19 patients at a higher risk of death.


Single-shot measurement of the orbital-angular-momentum spectrum of light.
The existing methods for measuring the orbital-angular-momentum (OAM) spectrum suffer from issues such as poor efficiency, strict interferometric stability requirements, and too much loss. Furthermore, most techniques inevitably discard part of the field and measure only a post-selected portion of the true spectrum. Here, we propose and demonstrate an interferometric technique for measuring the true OAM spectrum of optical fields in a single-shot manner. Our technique directly encodes the OAM-spectrum information in the azimuthal intensity profile of the output interferogram. In the absence of noise, the spectrum can be fully decoded using a single acquisition of the output interferogram, and, in the presence of noise, acquisition of two suitable interferograms is sufficient for the purpose. As an important application of our technique, we demonstrate measurements of the angular Schmidt spectrum of the entangled photons produced by parametric down-conversion and report a broad spectrum with the angular Schmidt number 82.1.


The Transient Receptor Potential Vanilloid 1 Antagonist Capsazepine Improves the Impaired Lung Mechanics during Endotoxemia.
Acute lung injury (ALI) caused by systemic inflammatory response remains a leading cause of morbidity and mortality in critically ill patients. Management of patients with sepsis is largely limited to supportive therapies, reflecting an incomplete understanding of the underlying pathophysiology. Furthermore, there have been limited advances in the treatments for ALI. In this study, lung function and a histological analysis were performed to evaluate the impact of transient receptor potential vanilloid-1 receptor (TRPV1) antagonist (capsazepine; CPZ) on the lipopolysaccharide (LPS)-induced lung injury in mice. For this, adult mice pre-treated with CPZ or vehicle received intraperitoneal injections of LPS or saline and 24 hr after, the mice were anaesthetized, and lung mechanics was evaluated. The LPS-challenged mice exhibited substantial mechanical impairment, characterized by increases in respiratory system resistance, respiratory system elastance, tissue damping and tissue elastance. The pre-treatment with CPZ prevented the increase in respiratory system resistance and decreased the increase in tissue damping during endotoxemia. In addition, mice pre-treated with CPZ had an attenuated lung injury evidenced by reduction on collapsed area of the lung parenchyma induced by LPS. This suggests that the TRPV1 antagonist capsazepine has a protective effect on lung mechanics in ALI during endotoxemia and that it may be a target for enhanced therapeutic efficacy in ALI.


Spaces and networks of genetic knowledge making: the 'geneticisation' of heart disease.
The 'geneticisation' of health, medicine and the body is extending from single-gene to multi-factorial conditions such as heart disease. Adopting 'Actor Network Theory', the paper argues that the making of genetic knowledge occurs in spaces and networks where contested knowledges necessarily produce a geneticisation that is neither certain nor complete. Drawing on empirical research in a coronary care unit in Glasgow, Scotland, the paper sets out the network of consultants, rehabilitation nurses and people with heart disease and others who collectively, through contestation and the marshalling of knowledges by prominent social actors, produce an understanding of the role of genes in heart disease.


Shopping-cart-related injuries to children.
An estimated 24,200 children younger than 15 years, 20,700 (85%) of whom were younger than 5 years, were treated in US hospital emergency departments in 2005 for shopping cart-related injuries. Approximately 4% of shopping cart-related injuries to children younger than 15 years require admission to the hospital. Injuries to the head and neck represent three fourths of all injuries. Fractures account for 45% of all hospitalizations. Deaths have occurred from falls from shopping carts and cart tip-overs. Falls are the most common mechanism of injury and account for more than half of injuries associated with shopping carts. Cart tip-overs are the second most common mechanism, responsible for up to one fourth of injuries and almost 40% of shopping cart-related injuries among children younger than 2 years. Public-awareness initiatives, education programs, and parental supervision, although important, are not enough to prevent these injuries effectively. European Standard EN 1929-1:1998 and joint Australian/New Zealand Standard AS/NZS 3847.1:1999 specify requirements for the construction, performance, testing, and safety of shopping carts and have been implemented as national standards in 21 countries. A US performance standard for shopping carts (ASTM [American Society for Testing and Materials] F2372-04) was established in July 2004; however, it does not adequately address falls and cart tip-overs, which are the leading mechanisms of shopping cart-related injuries to children. The current US standard for shopping carts should be revised to include clear and effective performance criteria for shopping cart child-restraint systems and cart stability to prevent falls from carts and cart tip-overs. This is imperative to decrease the number and severity of shopping cart-related injuries to children. Recommendations from the American Academy of Pediatrics regarding prevention of shopping cart-related injuries are included in the accompanying policy statement.


Determination of the in situ forces and force distribution within the human anterior cruciate ligament.
The in situ forces and their distribution within the human anterior cruciate ligament (ACL) can clarify this ligament's role in the knee and help to resolve controversies regarding surgical treatment of ACL deficiency. We used a universal force-moment sensor (UFS) to determine the magnitude, direction, and point of application of the in situ forces in the ACL in intact human cadaveric knees. Unlike previous studies, this approach does not require surgical intervention, the attachment of mechanical devices to or near the ACL, or a priori assumptions about the direction of in situ force. Anterior tibial loads were applied to intact knees, which were limited to 1 degree of freedom at 30 degrees flexion. The in situ forces developed in the ACL were lower than the applied force for loads under 80 N, but larger for applied loads of more than 80 N. The direction of the force vector corresponded to that of the anteromedial (AM) portion of the ACL insertion on the tibial plateau. The point of force application was located in the posterior section of the anteromedial portion of the tibial insertion site. The anterior and posterior aspects of the anteromedial portion of the ACL supported 25% and 70% of the in situ force, respectively, with the remainder carried by the posterolateral portion. We believe that the data obtained with this new UFS methodology improves our understanding of the role of the ACL in knee function, and that this methodology can be easily extended to study the function of other ligaments.


Analytical study of pustular eruptions in neonates.
Pustular eruptions are commonly encountered in neonatal practice. Much confusion exists among clinicians because of the similarity in clinical lesions, paucity of relevant literature, and varied nomenclature used for these diseases. This often results in inappropriate diagnoses and therapies, besides subjecting the neonates to invasive and traumatic investigative procedures. We conducted a comprehensive study of pustular eruptions in 100 neonates, using the clinical examination and simple laboratory tests to arrive at a practical diagnostic and therapeutic approach to this problem. Of the 100 neonates with pustular eruptions, 36% were in the early neonatal period (first week of life). A slight male preponderance with a male:female ratio of 1:0.79 was observed. The majority of the families of these infants had poor socioeconomic status (96%) and were living in slums (71%). A study of their educational status revealed that 54% of the mothers were uneducated. Fifty-seven percent of the neonates were born at home. The clinical pattern of diseases among these neonates was that 58% of them had infections [impetigo (23%), intertrigo (14%), scabies (6%), and viral diseases (6%)]. Noninfectious diseases (42%) included miliaria pustulosa, erythema toxicum neonatorum, epidermolysis bullosa, and contact dermatitis. Simple laboratory investigations helpful in establishing the diagnosis were smears processed with Gram (24%) and Giemsa (39%) stains and wet mounts with 10% potassium hydroxide (KOH) solution (27%) for direct microscopic examination. More than half (53%) of the patients required no specific treatment except for counseling and medications to alleviate symptoms, while others with an infectious etiology responded to topical and or systemic antibiotics/antifungals. Pustular eruptions in neonates include both infectious and noninfectious diseases. Simple laboratory tests such as Gram- and Giemsa-stained smears, direct microscopy with 10% KOH wet mounts, bacterial and fungal cultures are helpful in establishing the diagnosis and occasionally skin biopsy is needed. A practical diagnostic and therapeutic approach to this problem is discussed.


Maintenance of efficacy and safety of rabeprazole in children with endoscopically proven GERD.
The aim of the present study was to evaluate 24-week maintenance of efficacy and safety of rabeprazole in children with endoscopically proven gastroesophageal reflux disease (GERD). Children ages 1 to 11 years who achieved endoscopic/histologic healing (defined as grade 0 of the Hetzel-Dent Classification scale and/or grade 0 of the Histological Features of Reflux Esophagitis scale) in a 12-week treatment phase were continued on the same dose for an additional 24 weeks during the maintenance phase. The dose was determined by weight: children weighing 6 to 14.9 kg (low-weight cohort) received 5 or 10 mg and children weighing ≥ 15 kg (high-weight cohort) received 10 or 20 mg. Healing was maintained in 90% of children (100% [low-weight cohort]; 89% [10 mg, high-weight cohort]; 85% [20 mg, high-weight cohort]). The Total GERD Symptom and Severity score continued to improve slightly in all of the children across all dose groups (P = 0.026) during the maintenance phase, except the 10-mg dose group (low-weight cohort), which experienced a slight worsening of 3.6 points. Overall, 71% children felt better on the GERD Symptom Relief score (P < 0.001); 95% of investigators and 92% of parent/caregivers rated "Good to Excellent" on the Global Treatment Satisfaction scale and Clinical Global Impressions Improvement scale, respectively. Overall incidence of treatment-emergent adverse events was 63%; upper respiratory tract infections (13%) and vomiting (11%) were the most commonly reported (>10%). Rabeprazole was effective in maintaining endoscopic/histologic healing during a 24-week maintenance period in children with endoscopically proven GERD. The clinical effect and safety profile were largely similar across dose groups.


2D(13)C-(13)C MAS NMR correlation spectroscopy with mixing by true (1)H spin diffusion reveals long-range intermolecular distance restraints in ultra high magnetic field.
An improved 2D (13)C-(13)C CP(3) MAS NMR correlation experiment with mixing by true (1)H spin diffusion is presented. With CP(3), correlations can be detected over a much longer range than with direct (1)H-(13)C or (13)C-(13)C dipolar recoupling. The experiment employs a (1)H spin diffusion mixing period tau(m) sandwiched between two cross-polarization periods. An optimized CP(3) sequence for measuring polarization transfer on a length scale between 0.3 and 1.0 nm using short mixing times of 0.1 ms < tau(m) < 1 ms is presented. For such a short tau(m), cross talk from residual transverse magnetization of the donating nuclear species after a CP can be suppressed by extended phase cycling. The utility of the experiment for genuine structure determination is demonstrated using a self-aggregated Chl a/H(2)O sample. The number of intramolecular cross-peaks increases for longer mixing times and this obscures the intermolecular transfer events. Hence, the experiment will be useful for short mixing times only. For a short tau(m) = 0.1 ms, intermolecular correlations are detected between the ends of phytyl tails and ring carbons of neighboring Chl a molecules in the aggregate. In this way the model for the structure, with stacks of Chl a that are arranged back to back with interdigitating phytyl chains stretched between two bilayers, is validated.


Radiated signal characteristics of marine vessels in the cepstral domain for shallow underwater channel.
This work examines the distribution of cepstral energy of the radiated signal of a marine vessel and the underwater channel modeled as a block-adaptive linear system. Detailed simulation analysis of the signal at the receiver of a passive sonar has led to the observation that, in the cepstral domain the radiated signal of a marine vessel largely occupies the lower cepstral indices while the underwater channel occupies the higher indices, such that for several range and depth conditions, the two can be separated out. This finding can facilitate the design of filters in the cepstral domain for reducing distortions due to the underwater channel. The work presents analytical justification and simulation studies in this regard.


[Fine structure of glioblastoma multiforme with "adenoid formation"].
Glioblastoma multiforme with "adenoid formation" (Kepes) in the temporal lobe of a 70 year old man was presented. In addition to the classical features of glioblastoma multiforme, the tumor presented a pattern of anastomosing trabeculae of polygonal cells, mimicking epithelial tubules, in a myxoid stroma. On electron microscopic examination, the tumor cells were devoid of well-developed cytoplasmic processes. The cytoplasm of some tumor cells contained glycogen particles and lipid vacuoles in addition to usual organelles. The cell surface was partly covered by basal lamina associated with half desmosomes and had occasional filopodia-like cytoplasmic projections. A few tumor cells contained a dense intracytoplasmic accumulation of glial filaments. Intercellular junctional complexes were poorly developed. There was no evidence of differentiation of tumor cells toward ependymal cells or epithelial cells. These electron microscopic findings suggest that this tumor is predominantly composed of immature astrocytes. In spite of a superficial resemblance to adenocarcinoma on light microscopy, the tumor cells are devoid of the differentiating features of epithelial neoplasms, and their ultrastructure is essentially similar to that of glioblastoma multiforme.


[Correlation between peripheral blood Th17 cells and carotid intima-media thickness in OSA patients].
Objective:To study the carotid intima-media thickness (IMT) level of OSA patients of different severity, the proportion of Th17 cells in peripheral blood and the mRNA level of nuclear transfer factor RORγt, and to explore the relationship between Th17 cells and atherosclerosis in OSA patients. Method:Sixty-two patients who underwent respiratory and sleep monitoring were selected and divided into three groups according to the AHI index: 15 patients in the normal control group(AHI<5), there were 22 cases in the mild group(AHI 5-15) and 25 cases in the moderate and severe group(AHI≥15). Carotid intima-media thickness(IMT) was measured in all subjects, the ratio of Th17 cells in peripheral blood monouelear cells(PBMC) were analysed by flow cytometry. The expression of RORγt mRNA were detected by real-time polymerase chain reaction. Result:The carotid IMT of patients in the normal control group, the mild OSA group and the moderate to severe OSA group were (0.74±0.21) mm, (1.09±0.23) mm and (1.60±0.30) mm, respectively. The moderate to severe group was higher than the mild group and the normal control group, the difference was statistically significant (P<0.01). The proportion of Th17 in peripheral blood of the three groups was(2.54±0.20)%, (4.34±0.30)%, and (8.27±0.31)%, respectively. The moderate to severe group was significantly higher than the mild group and the control group (P<0.01), the difference was statistically significant. The relative mRNA expression levels of RORγt in the three groups were 0.92±0.24, 2.60±0.59, and 4.93±0.72, respectively. The moderate to severe group was significantly higher than the mild group and the control group (P<0.01), the difference was statistically significant. The proportion of Th17 in peripheral blood and the relative expression of RORvt mRNA were positively correlated with the carotid IMT (r value was 0.80, 0.78, respectively, all P<0.01). Conclusion:Th17 cells differentiation is increased in OSA patients, and Th17 cells are correlated with indicators reflecting the progression of atherosclerosis. Th17 cells may be involved in the development of atherosclerosis in OSA patients.


Percutaneous intervention for renovascular disease: rationale and patient selection.
The anatomic diagnosis of renovascular disease is increasing in frequency due to the advent of sophisticated non-invasive imaging modalities such as MRA (Magnetic Resonance Angiography) and renal angiography at the time of cardiac catheterization. Despite this fact, the investigation and appropriate management of renovascular disease has remained a controversial topic. This review addresses the clinical syndromes associated with renal artery stenosis (RAS) and the published data guiding appropriate patient selection for revascularization. There is a growing literature in support of renal revascularization as an aid in improving anti-hypertensive control, preserving renal function, and easing the management of congestive heart failure. Meanwhile, technological advances have allowed intervention in an expanding pool of eligible patients. One such technology is the atheroembolic protection device, which may soon allow renal salvage in patients with significant baseline renal impairment that were previously denied intervention for fear of worsening renal function. The data reviewed herein helps to identify patients that will benefit from renal revascularization. Large-scale, randomized data further defining the role of renal revascularization and optimal patient selection is still needed.


Single or multiple HPV types in cervical cancer and associated metastases.
Almost all cervical cancers are human papillomavirus (HPV)-positive. Some aspects of HPV carcinogenesis, such as factors involved in the transformation process and the mono- or polyclonal origin of the carcinogenic process, need to be defined. The latter aspect is addressed in our study. Cervical samples were collected from 102 patients with squamous cell carcinoma. The HPV positivity was established by PCR analysis performed using consensus and specific primers for the L1 and E6/E7 regions, respectively. Eighty-seven samples were positive for the L1 gene and 5 for the E6/E7 genes. Overall, 92 samples contained segments of HPV-DNA (90.2%). HPV-16 was most frequently found either alone or associated with other genotypes (63%). All genotypes identified as a single infection, except HPV-73, belonged to the high-risk HPV group. Among multiple infections, the HPV-31+54 couple was the most frequent. The presence of two genotypes in a primary tumor raises the question of their distribution in a single tumor cell. We attempted to answer this question by comparing the HPV patterns in primary tumors and metastases, considering that metastases derive from cell clones released from the primary tumor. The HPV patterns of primary tumors and metastases overlapped in most patients, even when primary tumors contained a double genotype, thus suggesting that single tumor cells may contain multiple HPV genotypes.


Raised plasma concentrations of parathyroid hormone related peptide in hypercalcemic multiple myeloma.
In order to clarify the pathogenesis of hypercalcemia in multiple myeloma, we measured plasma levels of parathyroid hormone related peptide (PTHrP), tumor necrosis factor alpha (TNF-alpha), tumor necrosis factor beta (TNF-beta), intact PTH and, serum 1,25-dihydroxyvitamin D in fifteen patients of multiple myeloma. We also measured serum levels of inorganic phosphorus (iP) and alkalinephosphatase activity (ALP). No significant differences in iP (3.2 +/- 0.4 vs. 4.0 +/- 2.2 mg/dl), ALP (150 +/- 28 vs. 335 +/- 305 IU/l) 1,25(OH)2 D (31.5 +/- 17.0 vs. 23.3 +/- 11.2 pg/ml) or TNF-alpha (7.8 +/- 2.1 vs. 8.0 +/- 2.0 pg/ml) were observed between normocalcemic and hypercalcemic patients. Plasma iPTH levels in hypercalcemic patients were significantly lower than those in normocalcemic patients (28.5 +/- 9.4 vs. 16.3 +/- 5.6 pg/ml, p = 0.01). Plasma levels of TNF-beta were less than 15.6 pg/ml in all subjects. On the other hand, the frequency of patients with abnormally high plasma levels of PTHrP was significantly greater (2/9 for normocalcemia vs 5/6 for hypercalcemia, chi 2 = 5.20, p = 0.02) in patients with hypercalcemia than in normocalcemic patients. Furthermore, a significant positive relationship between plasma PTHrP levels and corrected serum calcium levels (cCa) was observed using Spearman's correlation analysis by rank in fifteen myeloma cases (rs = 0.66, p = 0.013). These results suggest that PTHrP might be involved in the elevation of serum calcium levels in hypercalcemic myeloma patients. However, a few cases exhibit normocalcemia despite elevated plasma PTHrP levels or hypercalcemia without high plasma PTHrP levels. Therefore, further studies are necessary to elucidate the pathogenesis of hypercalcemia in multiple myeloma.


Oxidative Stress during HIV Infection: Mechanisms and Consequences.
It is generally acknowledged that reactive oxygen species (ROS) play crucial roles in a variety of natural processes in cells. If increased to levels which cannot be neutralized by the defense mechanisms, they damage biological molecules, alter their functions, and also act as signaling molecules thus generating a spectrum of pathologies. In this review, we summarize current data on oxidative stress markers associated with human immunodeficiency virus type-1 (HIV-1) infection, analyze mechanisms by which this virus triggers massive ROS production, and describe the status of various defense mechanisms of the infected host cell. In addition, we have scrutinized scarce data on the effect of ROS on HIV-1 replication. Finally, we present current state of knowledge on the redox alterations as crucial factors of HIV-1 pathogenicity, such as neurotoxicity and dementia, exhaustion of CD4+/CD8+ T-cells, predisposition to lung infections, and certain side effects of the antiretroviral therapy, and compare them to the pathologies associated with the nitrosative stress.


Monitoring antibody aggregation in early drug development using Raman spectroscopy and perturbation-correlation moving windows.
In this study, we demonstrate the sensitivity of two-dimensional perturbation-correlation moving windows (PCMW) to characterize conformational transitions in antibodies. An understanding of how physiochemical properties affect protein stability and instigate aggregation is essential for the engineering of antibodies. In order to establish the potential of PCMW as a technique for early identification of aggregation mechanisms during antibody development, five antibodies with varying propensity to aggregate were compared. Raman spectra were acquired, using a 532 nm excitation wavelength as the protein samples were heated from 56 to 78 °C and analyzed with PCMW. Initial principal component analysis confirmed a trend between the observed spectral variations and increasing temperature for all five samples. Analysis using PCMW revealed that when spectral variations were directly related to temperature, distinct differences in conformational changes could be determined between samples related to protein stability, providing a greater understanding of the aggregation mechanisms of problematic antibody variants.


Telephone-delivered behavioral health interventions for people living with HIV: patients' perspectives from a qualitative study.
People living with HIV (PLWH) often experience mental health concerns as well as difficulties with medication adherence; they also report barriers to receipt of health services. Telephone-delivered interventions can overcome some of these barriers. To obtain patients' perspectives on telephone-delivered behavioral health services, we conducted a qualitative study with patients who participated in one of two telephone-delivered interventions (mindfulness training, health coaching) in a research trial. Patients (N = 42; M age = 46 years, 50% female, 26% Black) participated in semi-structured qualitative interviews after completing the study. They identified several advantages (e.g., being able to schedule sessions more flexibly compared to in-person appointments, ease of developing rapport with interventionists) as well as occasional challenges of phone delivery (e.g., network connectivity). Overall, PLWH view telephone-delivery as a convenient and flexible method to engage in behavioral health interventions.


The effect of short message service intervention on glycemic control in diabetes: a systematic review and meta-analysis.
Background: Compared with traditional outpatient follow up, short message service (SMS) provides more convenience for diabetes self-management. However, the feasibility, effectiveness, and satisfaction of SMS intervention remain unclear.Methods: A systematic retrieval of databases, including PubMed, EMBASE, and Cochrane Library, was used to evaluate the effect of SMS on the diabetes glycemic control. Complete quantitative reports on the changes of glycosylated hemoglobin (HbA1c) before and after intervention were collected. The study type was limited to randomized controlled trials (RCTs).Results: 13 RCTs were identified as eligible for this subject. Overall result revealed a statistical decline of HbA1c by -0.62% (95% CI -0.82 to -0.41). The longest intervention duration was 12 months with the noteworthy improvement of HbA1c by -1.63% (-2.27 to -0.99). Compared with control groups, five trials quantitatively demonstrated a significant decline in fasting plasma glucose (FPG) by -0.45 (95% CI -0.7 to -0.19) and -1.05 (95% CI -1.35 to -0.75) in 2-h postprandial blood glucose (2hPBG).Conclusions: This meta-analysis demonstrated that text message intervention indeed leads to a decline in HbA1c and improvement of blood glucose control. No convincing evidence was found on quality of life improvement, satisfaction, body mass index (BMI), blood lipid levels, the frequency of hypoglycemia, self-monitoring of blood glucose or complications reduction.


1,3-Bridged p-methyloctahomotetraoxacalix[4]arene-bis-crown-3.
The title compound, 13,21,35,43-tetramethyl-3,6,9,17,25,28,31,39,46,49-decaoxaheptacyclo[126.96.36.199(11,33).0(2,41).0(10,15).0(19,24).0(32,37)]pentaconta-1,10,12,14,19,21,23,32,34,36,41,43-dodecaene, C(44)H(52)O(10), differs from previously reported 1,3-bridged calix[4]arene[bond]bis-crown compounds in having an enlarged calixarene ring and shorter polyoxyethylene bridges. The cavity is partly filled by the bridges.


Development of new canine and feline preventive healthcare guidelines designed to improve pet health.
The American Veterinary Medical Association (AVMA) and American Animal Hospital Association (AAHA) have jointly introduced the first Canine and Feline Preventive Healthcare Guidelines. These consensus statements provide veterinarians with a new resource for improving patient care by emphasizing the value and scope of regular pet examinations. The two guidelines provide complete recommendations for comprehensive preventive healthcare programs, published as accessible, single-page documents. The guidelines are based on the subjective-objective-assessment-plan (SOAP) methodology of case management, a proven approach traditionally used with sick or injured patients. This logical and disciplined process is equally applicable to healthy patients and is designed to consistently deliver optimal patient care. The guidelines recommend visits for health examinations on at least an annual basis, recognizing that for many pets, more frequent visits may be appropriate, depending on the individual needs of the patient. The guidelines also provide detailed diagnostic, therapeutic, prevention, and follow up plans, to be accompanied by appropriate documentation. The inclusive content and concise format of the guidelines are designed to maximize their practical value and make them easy to implement.


Increased trapezius pain sensitivity is not associated with increased tissue hardness.
Fatiguing exercise can affect muscle pain sensitivity and muscle hardness, as seen with work-related neck and shoulder pain. Objective methods to assess muscle pain sensitivity are important because the reliability of manual assessment is generally poor. The aim of this study was (1) to compare coexistence of tender points identified by manual palpation and pressure algometry or hardness assessments and (2) to examine the influence of exercise on muscle pain sensitivity and hardness. Fourteen sites in the upper trapezius muscle were selected for assessments in 12 healthy subjects. Pressure pain thresholds and muscle hardness were examined by computer-controlled pressure algometry at baseline, immediately after static or dynamic exercise, and 20 minutes after static or dynamic exercise. Before recording of pressure pain thresholds, the trapezius muscle was examined for tender points by manual palpation. Two sites with low pressure pain thresholds were typical locations for tender points, and these were the least hard sites. However, manually detected tender points were often (29%) not colocalized with most sensitive sites according to the pressure algometry. A heterogeneous distribution of pressure pain sensitivity and muscle hardness was found in the upper trapezius. The short duration of exercise until exhaustion did not change muscle sensitivity or muscle hardness in asymptomatic muscles. This study confirms clinical findings with heterogeniosity in pain sensitivity and hardness across the upper trapezius muscle. Developments of new techniques that objectively can identify tender points are important, but thus far, manual palpation is best clinical practice.


Surplus zinc is handled by Zym1 metallothionein and Zhf endoplasmic reticulum transporter in Schizosaccharomyces pombe.
Homeostatic mechanisms prevent the accumulation of free zinc in the cytoplasm, raising questions regarding where surplus zinc is stored and how it is delivered to and from these stores. A genetic screen for zinc hypersensitivity in Schizosaccharomyces pombe identified a missense mutation truncating Zhf, an endoplasmic reticulum transporter. These cells were approximately 5-fold more zinc-sensitive than other independent mutants. The targeted disruption of zhf prevented growth on low zinc medium and caused hypersensitivity to elevated zinc/cobalt but resistance to cadmium. The exposure to elevated zinc but not copper also promotes the accumulation of transcripts encoding a metallothionein designated Zym1. The Sty1 pathway is required for maximal zym1 expression but is not obligatory for zinc perception. The targeted disruption of zym1 impaired cadmium tolerance but only slightly impaired zinc tolerance, whereas zym1 overexpression substantially rescued zinc hypersensitivity of zhf(-) cells. Four equivalents of zinc were displaced from Zym1 by up to 12 equivalents of p-(hydroxymercuri)phenylsulphonate. Zym1 thiols react rapidly with 5,5'-dithiobis-(2-nitrobenzoic acid) compared with bacterial zinc metallothionein (6.8 and 0.2 x 10(-4) s(-1), respectively). Zym1 is unlike known fungal metallothioneins that are induced by and sequester copper but not zinc. Less zinc but normal cadmium was accumulated by zym1Delta, consistent with zinc sequestration by Zym1 in vivo.


A Case of Pneumonia Caused by Pneumocystis jirovecii Resistant to Trimethoprim-Sulfamethoxazole.
A 50-year-old male visited the outpatient clinic and complained of fever, poor oral intake, and weight loss. A chest X-ray demonstrated streaky and fibrotic lesions in both lungs, and chest CT revealed multifocal peribronchial patchy ground-glass opacities with septated cystic lesions in both lungs. Cell counts in the bronchoalveolar lavage fluid revealed lymphocyte-dominant leukocytosis, and further analysis of lymphocyte subsets showed a predominance of cytotoxic T cells and few T helper cells. Video-assisted wedge resection of the left upper lobe was performed, and the histologic examination was indicative of a Pneumocystis jirovecii infection. Trimethoprim-sulfamethoxazole (TMP-SMX) was orally administered for 3 weeks; however, the patient complained of cough, and the pneumonia was aggravated in the follow-up chest X-ray and chest CT. Molecular studies demonstrated mutations at codons 55 and 57 of the dihydropteroate synthase (DHPS) gene, which is associated with the resistance to TMP-SMX. Clindamycin-primaquine was subsequently administered for 3 weeks replacing the TMP-SMX. A follow-up chest X-ray showed that the pneumonia was resolving, and the cough was also alleviated. A positive result of HIV immunoassay and elevated titer of HCV RNA indicated HIV infection as an underlying condition. This case highlights the importance of careful monitoring of patients with P. jirovecii pneumonia (PCP) during the course of treatment, and the molecular study of DHPS mutations. Additionally, altering the anti-PCP drug utilized as treatment must be considered when infection with drug-resistant P. jirovecii is suspected. To the best of our knowledge, this is the first case of TMP-SMX-resistant PCP described in Korea.


Regiocontrolled synthesis of pyrrole-2-carboxaldehydes and 3-pyrrolin-2-ones from pyrrole Weinreb amides.
A regiocontrolled synthesis of 3,4-disubstituted pyrrole-2-carboxaldehydes was completed in two steps from acyclic starting materials. A Barton-Zard pyrrole synthesis between N-methoxy-N-methyl-2-isocyanoacetamide and alpha-nitroalkenes or beta-nitroacetates provided N-methoxy-N-methyl pyrrole-2-carboxamides (pyrrole Weinreb amides), which were converted into the corresponding pyrrole-2-carboxaldehydes by treatment with lithium aluminum hydride. A regioselective oxidation of the pyrrole-2-carboxaldehydes gave the corresponding 3,4-disubstituted 3-pyrrolin-2-ones.


Eosinophil-Rich Acute Febrile Neutrophilic Dermatosis in a Patient With Enteropathy-Associated T-cell Lymphoma, Type 1.
The presence of eosinophils within the neutrophilic infiltrates of acute febrile neutrophilic dermatosis (Sweet syndrome) is documented in the literature. Here, the authors describe a case of eosinophil-rich acute febrile neutrophilic dermatosis in the setting of new onset enteropathy-associated T-cell lymphoma (EATL), type 1. Histopathologic evaluation of the skin biopsies demonstrated a mixed superficial perivascular and inflammatory infiltrate composed of neutrophils, lymphocytes, and abundant eosinophils. EATL, type 1 is an aggressive although rare primary intestinal lymphoma that may be associated with celiac disease. This lymphoma is associated with a poor prognosis due to treatment resistance or bowel perforation. To the authors' knowledge, Sweet syndrome has not been reported in a patient with EATL.


The creation of the client reflexivity scale: A measure of minute fluctuations in self-awareness and exploration.
to design and pilot a reliable observer-based scale of client reflexivity that can be used on short segments of time ("coding intervals") across therapy sessions. Reflexivity was defined as the level of a client's awareness and exploration of his or her interiority. Interiority was defined as thoughts, feelings, sensations, intentions, and desires. The Client Reflexivity Scale (CRS) was designed through the coding of public access therapy videos featuring demonstrations of therapy. Along with the Experiencing Scale, the CRS was then piloted on one good outcome and one poor outcome session of cognitive-behavioural therapy for anxiety. Each session of therapy featured the same therapist but different clients. Two raters coded the sessions. Weighted kappas for inter-rater reliability ranged from 0.74 to 0.81. The level of reflexivity was significantly higher in the good outcome session than the poor outcome session, though the trajectory of reflexivity for both sessions was the same. The CRS was also compared to the Experiencing Scale in order to determine similarities and differences between the scales. the CRS reliably measured reflexivity within the therapy sessions, and in the future can be layered with other process measures in order to map interactions across therapy sessions.


[An epidemiologic study of restless leg syndrome among retired military elders in Shanxi Province].
To explore the prevalence, diagnosis and treatment of restless leg syndrome (RLS) among military elders. A cross-sectional study was conducted among retired military elders in Shanxi Province from 2010 to 2011. According to age, they were divided into 4 groups to compare the prevalence of RLS and evaluate the severity of symptoms as "mild, moderate and severe". And the compositions of symptom severity were compared among different age groups. Also the rate of correct diagnosis of RLS was examined. Univariate analyses were conducted with SPSS 13. 0. There were 559 RLS patients in 3 472 elder subjects. The prevalence of RLS was 16. 1% and 15. 8% in male elders. The prevalence of RLS in male elders increased significantly with advancing age (P <0. 05). No significant difference existed in the compositions of symptom severity among different age groups of RLS patients (P > 0. 05). Only 3. 22% RLS patients were previously diagnosed and none received a proper therapy. The prevalence of RLS among military elders is higher than that of their foreign counterparts. The prevalence of RLS in male elders increases significantly with advancing age. Symptom severity of RLS has no obvious relationship with advancing age. Since the rate of correct diagnosis and therapy is rather low for RLS elders in China, we should pay greater attention to the knowledge of RLS.


Analysis of transcript-wide profile regulated by microsatellite instability of colorectal cancer.
Microsatellite instability-high (MSI-H) is a form of genomic instability present in 15% of colorectal cancer (CRC) cases. Several differential gene analyses have been conducted on CRC; however, none have specifically explored the differentially expressed genes in MSI-H CRC. Research on the different gene expressions between MSI-H CRC and microsatellite stable (MSS) CRC, and their different patterns of metastasis will provide invaluable insights for diagnosis, prognosis, and treatment. In this study, the differential expression of 46,602 genes were analyzed across 613 different tissue samples from The Cancer Genome Atlas (TCGA)-colon adenocarcinoma (COAD) and TCGA-rectum adenocarcinoma (READ) as part of a gene association analysis. R package TCGAbiolinks (version 2.18.0) was used to download the data set, and DESeq2 (version 1.30.1) was used for the differential gene analysis. The resulting genes were then analyzed for shared pathways with R package clusterProfiler (version 3.0.4). A total of 237 significantly differentially expressed genes (Padj<0.05) were found between MSI-H and MSS CRC. Differentially expressed genes include insulin like growth factor 2 (IGF2) and fibroblast growth factor 3 (FGF3), and the enriched pathways mostly involve hearing, digestive regulation, and neurogenesis.463 differentially expressed genes were found between metastatic and non-metastatic CRC. Notably differentially expressed genes in metastatic CRC include DEAD-box helicase 53 (DDX53) and adiponectin, C1Q and collagen domain containing (ADIPOQ), and enriched pathways include the immune system, cell adhesion, and cell signaling. For MSI-H CRC, a total of 34 genes were significantly differently expressed between metastatic and non-metastatic CRC. These include notum, palmitoleoyl-protein carboxylesterase (NOTUM), serpin family B member 2 (SERPINB2), and several keratin (KRT) genes, and the pathway analysis showed the major enrichment of the hormonal and secretion and regulation pathways. Of the differentially expressed genes in metastatic CRC, 25 were immunity related and include fatty acid binding protein 4 (FABP4), and the pathway analysis showed the enrichment of humoral immunity and lymphocyte regulation. Of the biologically plausible differentially expressed genes, the most notable were NOTUM, KRT6A, KRT14, SERPINB2, and serum amyloid A1 (SAA1). NOTUM, KRT6A, and KRT14 are active in the Wnt pathway. All five are also involved in various inflammation pathways.


[The mechanism of the reduction of protein catabolism following trauma and during sepsis using xylitol].
Total parenteral nutrition (TPN) after trauma and sepsis has two major goals. One is the reduction of enhanced protein catabolism; the second is the avoidance of enhancement of whole-body glucose turnover. Glucose and xylitol differ in their quantitative utilization rate after trauma and sepsis. Maximal glucose utilization is reduced during such states, while the utilization of xylitol is more than doubled. In order to investigate whether these differences are associated with beneficial effects with regard to whole-body glucose turnover rate of gluconeogenesis and protein sparing, we conducted two studies using animal models and two clinical studies. METHODS. For the determination of glucose and protein turnover, radioactive and stable isotope techniques were applied. In an animal model a primed constant infusion of 3-H-6-glucose, 14-C-1-alanine and 13-C-3-alanine and 14-C-U-acetate was used to determine total glucose appearance, gluconeogenesis from 3-C-precursors and alanine flux. In the human studies hepatic glucose production was determined by using a primed constant infusion of 6.6-D-2-glucose and urea synthesis rate was determined by a primed constant infusion of 2-N-15-urea. RESULTS. In the first rat model we were able to show that hypocaloric xylitol compared to glucose significantly reduced whole-body glucose turnover from 1741 +/- 232 mumol/h during glucose infusion to 449 +/- 49 mumol/h during xylitol infusion and gluconeogenesis from C-3 carbons form 382 +/- 24 mumol/h during glucose infusion to 155 +/- 39 mumol/h during xylitol infusion after a burn trauma. In a second septic rat model the exchange of glucose calories by xylitol in a proportion of 1:1 was associated with a significantly ameliorated N-balance from +144 +/- 90 mgN/kg body weight per day during glucose infusion to +699 +/- 80 mgN/kg body weight per day during glucose-xylitol infusion and a reduced 3-methyl-histidine excretion from 7.14 +/- 0.61 mumol/kg body wt. per day during glucose infusion to 4.10 +/- 0.56 mumol/kg per day during glucose-xylitol infusion, respectively. In two studies with surgical intensive care patients we were able to confirm the nitrogen-sparing properties of xylitol infusion, together with amino acids during hypocaloric feeding or during TPN with a glucose/xylitol mixture in a proportion of 1:1. From a basal urea production rate of 9.2 +/- 1.6 mumol/kg min. xylitol led to a significant reduction with 6.4 +/- 1.5 mumol/kg per min. Hepatic glucose production was significantly reduced during xylitol infusion from basal 4.8 +/- 0.6 mg/kg per min to 3.1 +/- 0.7 mg/kg per min, respectively. Equicaloric glucose in a dosage of 3 g/kg per day had no effect. During TPN glucose/xylitol, in a proportion of 1:1 at a total dosage of 0.24 g/kg per h, significantly reduced whole-body glucose turnover, endogenous glucose production and lactate concentrations compared to an isocaloric glucose infusion. DISCUSSION. In animal as well as in human studies hypocaloric xylitol as well as a glucose-xylitol mixture were more efficient in preserving body protein than glucose alone. Whole-body glucose turnover was significantly reduced during hypocaloric xylitol or glucose-xylitol infusion compared to isocaloric glucose infusion. During the acute phase after trauma we therefore recommend a carbohydrate supplementation of 3 g/kg body wt. per day using xylitol. During long-term TPN, a glucose-xylitol mixture in a proportion of 1:1 in a dosage of 3 g/kg body wt. per day each is recommended as energy source, together with amino acids and, if necessary, lipids.


Surgical and Endovascular Treatment of Saccular Posterior Inferior Cerebellar Artery Aneurysms: Systematic Review and Meta-Analysis.
The optimal treatment modality for saccular aneurysms of the posterior inferior cerebellar artery (PICA) remains unclear. A previous meta-analysis on the topic included a heterogenous study population, limiting the conclusions that can be drawn from its results. The aim of this study was to perform a systematic review and meta-analysis to compare outcomes of microsurgical and endovascular treatment (EVT) of these aneurysms. A search of 4 online databases was performed for studies describing the management of saccular PICA aneurysms. The primary outcome was complete aneurysm occlusion. Data were also collected on neurologic outcomes, cranial nerve palsies, and requirement for re-treatment. A random effects model was used for calculation of pooled proportions. Our protocol was registered with PROSPERO (CRD42021232784). A total of 17 studies were included in the final analysis, reporting the treatment outcomes of 455 aneurysms, with a mean follow-up of 20 months. The pooled occlusion rates were 94.8% (95% confidence interval [CI] 90.6%-97.8%) for surgical treatment and 69.1% (95% CI 55.0%-81.7%) for EVT. Pooled rates of good neurologic outcome (modified Rankin scale score ≤2, Glasgow Outcome Scale score ≥4) at last follow-up were 78.1% (95% CI 67.4%-87.1%) for surgery and 77.6% (95% CI 67.9%-86.0%) for EVT. This meta-analysis demonstrates that in the treatment of saccular PICA aneurysms, microsurgical clipping results in superior angiographic outcomes, similar functional outcomes, but higher rates of lower cranial nerve palsy compared with EVT. Further studies are required to assess the duration and severity of cranial nerve palsies following surgical treatment, and long-term aneurysm occlusion and the requirement for re-intervention following EVT.


Developing and Using Therapeutics for Emerging Infections.
This issue of Clinical Pharmacology & Therapeutics focuses on emerging infections. The outbreaks of the vaccine-preventable diseases (e.g., measles) and the emerging pathogens (e.g., Ebola) show us how small the world has become. These outbreaks also show the pressing need for effective public education and development of novel therapies. This issue covers various aspects of relevant therapeutic topics ranging from preclinical models, pharmacokinetics, pharmacodynamics, pharmacogenomics, and clinical trial results, to education efforts in this area. Pharmacokinetic/dynamic modeling had an appreciable role in reducing the morbidity and mortality associated with human immunodeficiency virus and hepatitis C virus, recent emerging infections. However, these gains could be lessened by poor adherence to therapies, which has contributed to the development of multidrug-resistant tuberculosis. We must not forget lessons from previous infections, or they may reemerge.


Clinical epidemiology of suicide.
The epidemiologic identification of risk factors for suicide attempts and suicide deaths is important to clinical decision making and preventive public health efforts. The risk factors for suicide attempts include female sex, a recent stressful life event, methods of low lethality, impulsivity, and previous attempts. Risk factors for suicide deaths include a family history of suicide, male sex, and a psychiatric disorder. Suicide deaths in the "youth" birth cohort increased nearly 150% between 1960 and 1980. The term "youth" refers to those in the transitional period from adolescence to adulthood--roughly, between the ages of 18 and 30 years. An increase in substance abuse and in depressive disorders in this group paralleled the increase in suicide incidence. A novel, but frightening, tendency also noted in this group was social contagion--evidenced by clusters of suicides "mimicking" the suicide method and creating mini-epidemics.


Unleashing ferroptosis for cancer therapy with warfarin.
Ferroptosis holds promise for cancer therapy. A recent study by Yang et al. in Cell Metabolism reveals that VKORC1L1-mediated reduction of vitamin K inhibits ferroptosis and establishes a direct p53-VKORC1L1 link in its regulation. As warfarin can inhibit VKORC1L1, the study further underscores this drug's potential as a cancer therapy.