Helical computed tomography in the assessment of abdominal aortic pathology.
A pilot study was undertaken to evaluate the role of helical computed tomography in the assessment of abdominal aortic pathology. A total of 17 patients underwent intra-arterial digital subtraction of angiography (IADSA) and helical computed tomography, with eight patients undergoing subsequent operative intervention. A comparison of radiological findings between IADSA and helical computed tomography (CT) was made and, where applicable, a comparison was made with operative findings. Pathology included abdominal aortic aneurysm (AAA) (n = 12), thoraco-abdominal aneurysm (n = 2) and dissection (n = 1), graft distension following AAA repair (n = 1) and plaque haemorrhage in the distal aorta following percutaneous transluminal angioplasty (PTA) of the iliac artery (n = 1). Planned operative management as based on pre-operative helical CT imaging findings, in particular with reference to the type of graft used (straight or bifurcated) was not changed at operation. Our findings on helical CT in regards to AAA, thoroco-abdominal aneurysm and dissection correlated well with angiography and surgery findings.


Laser and light treatments for pilonidal cysts.
Pilonidal (nest of hair) cysts are foreign body reactions accompanied by chronic inflammation. Current accepted treatments include the traditional conservative treatments or aggressive surgery. However, these modalities exhibit a high rate of disease recurrence, especially in patients with hirsutism; therefore, affected patients often are subjected to repeated surgical interventions. This report describes 5 patients treated with either a diode laser or intense pulsed light (IPL), which produced results leaving the patients recurrence free. Four of 5 patients remained recurrence free for 7 months to more than 36 months; one patient experienced a recurrence after 36 months, which was longer than his previous remission. These results suggest laser and IPL technologies are alternatives to traditional surgical intervention, providing potentially longer disease-free intervals and fewer recurrences.


The usefulness of the leuprolide stimulation test as a diagnostic method of idiopathic central precocious puberty in girls.
Central precocious puberty (CPP) diagnosis is based on clinical evaluation, but hormonal evaluation is crucial. The aim of the study was to evaluate the usefulness of the leuprolide stimulation test for diagnosis of idiopathic CPP. Sixty-one girls, aged 5-8 years, were evaluated retrospectively for premature breast development. According to clinical evolution, 28 had progressive puberty and 33 nonprogressive puberty. All underwent a leuprolide stimulation test. Cutoff points, sensitivity, and specificity for gonadotropins and estradiol were determined by receiver operating characteristic (ROC) curves. Cutoff points for CPP were: baseline LH: > 0.1 mUI/l, FSH: > 2.3 mUI/l, LH/FSH ratio: > 0.23, estradiol: > 12 pg/ml; and stimulated LH: > 5.5 mUI/l, LH/FSH ratio: > 0.24, estradiol: > 79.67 pg/ml. The best diagnostic efficiency for progressive puberty were stimulated LH/FSH ratio (sensitivity: 100%, specificity 94%) followed by stimulated LH (sensitivity: 93%, specificity: 100%). Stimulated LH/FSH ratio and LH resulted in the most useful parameters for the diagnosis of CPP. Stimulated estradiol did not add more information.


Neofunctionalization of Toll Signaling in Insects: From Immunity to Dorsoventral Patterning.
Toll signaling plays a crucial role in pathogen defense throughout the animal kingdom. It was discovered, however, for its function in dorsoventral (DV) axis formation in Drosophila. In all other insects studied so far, but not outside the insects, Toll is also required for DV patterning. However, in insects more distantly related to Drosophila, Toll's patterning role is frequently reduced and substituted by an expanded influence of BMP signaling, the pathway implicated in DV axis formation in all major metazoan lineages. This suggests that Toll was integrated into an ancestral BMP-based patterning system at the base of the insects or during insect evolution. The observation that Toll signaling has an immune function in the extraembryonic serosa, an early differentiating tissue of most insect embryos, suggests a scenario of how Toll was co-opted from an ancestral immune function for its new role in axis formation.


Stretch garment dermatitis.
A disease of the skin, not hitherto described, is caused by pressure or tension on the skin from the wearing of tight-fitting stretch garments such as "stretch bras," "stretch girdles" and "stretch socks." The condition is not due to chemical sensitization of fabrics, dyes or other additives but is of mechanical origin. The eruption may assume various clinical forms and may be characterized by a nondescript erythematous and eczematous appearance or may consist of an exaggeration, in the areas covered by the stretch garment, of already existing dermatosis such as lichen planus, psoriasis, acne vulgaris, discoid lupus erythematosus or atopic dermatitis.


Lymphoma of frontotemporal region with massive bone destruction and intracranial and intraorbital extension.
Primary non-Hodgkin's lymphoma with unilateral proptosis and diffuse involvement of the cra-nial vault and brain parenchyma is extremely rare. A 50-year-old woman developed a progressively increasing proptosis of her right eye, associated with a subcutaneous mass over the right frontotemporal region over the last 5 months. CT scan showed a high-density contrast-enhancing lesion with wide involvement of the cranium and intracranial and intraorbital extension. We performed a wedge biopsy for further analysis. Histological examination revealed that the tumor was non-Hodgkin's lymphoma. There was no evidence of systemic involvement. The patient received radiotherapy and was doing well at 18 months' follow-up. Primary malignant lymphoma involving the orbit and cranial vault is a rare malignancy, and treatment remains to be defined.


USP47 Promotes Tumorigenesis by Negative Regulation of p53 through Deubiquitinating Ribosomal Protein S2.
p53 is activated in response to cellular stresses such as DNA damage, oxidative stress, and especially ribosomal stress. Although the regulations of p53 by E3 ligase and deubiquitinating enzymes (DUBs) have been described, the cellular roles of DUB associated with ribosomal stress have not been well studied. In this study, we report that Ubiquitin Specific Protease 47 (USP47) functions as an important regulator of p53. We show that ubiquitinated ribosomal protein S2 (RPS2) by Mouse double minute 2 homolog (MDM2) is deubiquitinated by USP47. USP47 inhibits the interaction between RPS2 and MDM2 thereby alleviating RPS2-mediated suppression of MDM2 under normal conditions. However, dissociation of USP47 leads to RPS2 binding to MDM2, which is required for the suppression of MDM2, consequently inducing up-regulation of the p53 level under ribosomal stress. Finally, we show that depletion of USP47 induces p53 and therefore inhibits cell proliferation, colony formation, and tumor progression in cancer cell lines and a mouse xenograft model. These findings suggest that USP47 could be a potential therapeutic target for cancer.


Using Action-Mapping to Design a Non-Majors Neuroeconomics Course to Teach First-Year Collegiate Skills.
With its ability to address questions about how decisions are made and why, neuroeconomics is an excellent topic of study for college students at a variety of levels. In this paper we detail a neuroeconomics course specifically modified for undecided First-year students. One particularly daunting challenge was defining clear outcomes and delivering instruction at an appropriate level. We used Action-Mapping to achieve the course objectives of teaching collegiate skills applicable to any path of study or career while also delivering content suitable for credits in both a social science and natural science.


Comparison of the Results of Studies of Air Pollution Fungi Using the SAS Super 100, MAS 100, and Air IDEAL.
Although several air sampling devices for identifying and enumerating airborne microorganisms are commercially available, each poses some limitations. The aim of this study was to evaluate air pollution fungi using three such samplers: SAS Super 100, Microbiological Air Sampler (MAS) 100, and Air IDEAL. Mycological air was taken from the cellars of a 17th-century church in Siemiatycze, Poland, and the nearby outdoor environment. With samplers placed 1.5 m above the floor, microbial flora in air samples collected inside and outside the cellar were detected. The number of colony-forming units (CFU) of fungi obtained with the three samplers from the cellars and outdoor environment differed; the most CFU were obtained with the Air IDEAL and the least with the SAS Super 100. Significant differences emerged in CFUs collected from air samples with the MAS 100 and SAS Super 100, on the one hand, and the SAS Super 100 and Air IDEAL, on the other. Otherwise, results among the samplers were different. More Cladosporium species were collected with the MAS 100 sampler, whereas more Fusarium and Aspergillus species were collected with the Air IDEAL sampler. Significant differences among CFU/m³ values among the tested sites depended on the sampler used.


Emergency department visits for dental problems not associated with trauma in Alberta, Canada.
The objective of this report was to describe the frequency of emergency department (ED) visits for dental problems not associated with trauma (DPNAT) in Alberta, Canada, over a 5-year period. In Alberta, ED visits for DPNAT between 1 January 2011 and 30 April 2016 were identified using the codes from the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada (ICD-10-CA). The codes for DPNAT range from K00 to K14, described as diseases of the oral cavity, salivary glands and jaws. The data were gathered from the National Ambulatory Care Reporting System (NACRS) database and from the Alberta Real Time Syndromic Surveillance Net (ARTSSN). The information gathered on ED visits for DPNAT was related to the primary diagnosis of the discharge disposition of the visits. During the study period, there were a total of 147,357 ED visits for DPNAT in Alberta. The visits were made by 111,362 individuals, representing 1.3 visits per person. Among all ED visits, a prevalence of 1.2% of ED visits for DPNAT was observed. The most prevalent primary diagnosis of ED visits for DPNAT was for diseases of pulp and periapical tissues (K04), such as periapical abscess, representing 45.0% of all visits, followed by disorders of teeth and supporting structures (K08), such as toothache, representing 18.8% of all visits. The majority of the visits were made by patients from 20 to 44 years of age (52.2%). North and Calgary Alberta Health Service (AHS) Zones were those with the highest occurrence of ED visits (31.9% and 24.5%, respectively). ED visits for dental problems were more common than visits for other general health conditions, such as diabetes and asthma. The frequency of ED visits for DPNAT suggests barriers faced by the population in accessing dental care resources, especially for urgent dental needs. Policy efforts and political will are needed to provide alternative options for seeking emergency dental care.


Nonpeptide renin inhibitors with good intraduodenal bioavailability and efficacy in dog.
The aim of this study was the discovery of nonpeptide renin inhibitors with much improved oral absorption, bioavailability, and efficacy, for use as antihypertensive agents. Our prior efforts led to the identification of A-74273 [1,R = 3-(4-morpholino)propyl], with a bioavailability of 26 +/- 10% [10 mg/kg intraduodenally (id), dog]. In vivo metabolism studies of A-74273 showed that the morpholino moiety underwent metabolic degradation. Computer modeling of A-74273 bound to renin indicated that the C-terminus was involved in a hydrogen-bonding network. New C-terminal groups were examined in two series of nonpeptides for effects on renin binding potency, lipophilicity (log P), and aqueous solubility. Those groups which possessed multiple hydrogen-bonding ability (3,5-diaminotriazole, cyanoguanidines, morpholino) provided particularly potent renin binding. Intraduodenal bioavailabilities of selected compounds, evaluated in rats, ferrets, and dogs, were higher for inhibitors with moderate solubility as well as moderate lipophilicity, in general. Although the absolute values varied substantially among species, the relative ordering of the inhibitors in terms of absorption and bioavailability was reasonably consistent. Such well absorbed inhibitors (e.g. 41, 44, and 51) were demonstrated as highly efficacious hypotensive agents in the salt-depleted dog. We report here the discovery of a series of efficacious nonpeptide renin inhibitors based on the 3-azaglutaramide P2-P4 replacement, the best of which showed id bioavailabilities > 50% in dog.


Differentiation between pleomorphic adenoma and schwannoma in the parapharyngeal space: histogram analysis of apparent diffusion coefficient.
To elucidate the differences between pleomorphic adenomas and schwannomas occurring in the parapharyngeal space by histogram analyses of apparent diffusion coefficient (ADC) values measured with diffusion-weighted MRI. This retrospective study included 29 patients with pleomorphic adenoma and 22 patients with schwannoma arising in the parapharyngeal space or extending into the parapharyngeal space from the parotid region. Using pre-operative MR images, ADC values of tumor lesions showing the maximum diameter were measured. The regions of interest for ADC measurement were placed by contouring the tumor margin, and the histogram metrics of ADC values were compared between pleomorphic adenomas and schwannomas regarding the mean, skewness, and kurtosis by Wilcoxon's rank sum test. Subsequent to the primary analysis which included all lesions, we performed two subgroup analyses regarding b-values and magnetic field strength used for MRI. The mean ADC values did not show significant differences between pleomorphic adenomas and schwannomas for the primary and subgroup analyses. Schwannomas showed higher skewness (p = 0.0001) and lower kurtosis (p = 0.003) of ADC histograms compared with pleomorphic adenomas in the primary analysis. Skewness was significantly higher in schwannomas in all the subgroup analyses. Kurtosis was consistently lower in schwannomas but did not reach statistical significance in one subgroup analysis. Skewness and kurtosis showed significant differences between pleomorphic adenomas and schwannomas occupying the parapharyngeal space, but the mean ADC values did not. Our results suggest that the skewness and kurtosis of ADC histograms may be useful in differentiating these two parapharyngeal tumors.


Group B streptococcal endocarditis after elective abortion in an adolescent.
We describe a case of group B streptococcal endocarditis in a 15-year-old girl after an elective abortion. There are only 6 reports of group B streptococcal endocarditis in older children. It is a well described but rare complication of surgical abortions, and tends to have an aggressive course.


ACEH/ACE2 is a novel mammalian metallocarboxypeptidase and a homologue of angiotensin-converting enzyme insensitive to ACE inhibitors.
A human zinc metalloprotease (termed ACEH or ACE2) with considerable homology to angiotensin-converting enzyme (ACE) (EC 18.104.22.168) has been identified and subsequently cloned and functionally expressed. The translated protein contains an N-terminal signal sequence, a single catalytic domain with zinc-binding motif (HEMGH), a transmembrane region, and a small C-terminal cytosolic domain. Unlike somatic ACE, ACEH functions as a carboxypeptidase when acting on angiotensin I and angiotensin II or other peptide substrates. ACEH may function in conjunction with ACE and neprilysin in novel pathways of angiotensin metabolism of physiological significance. In contrast with ACE, ACEH does not hydrolyse bradykinin and is not inhibited by typical ACE inhibitors. ACEH is unique among mammalian carboxypeptidases in containing an HEXXH zinc motif but, in this respect, resembles a bacterial enzyme, Thermus aquaticus (Taq) carboxypeptidase (EC 184.108.40.206). Collectrin, a developmentally regulated renal protein, is homologous with the C-terminal region of ACEH but has no similarity with ACE and no catalytic domain. Thus, the ACEH protein may have evolved as a chimera of a single ACE-like domain and a collectrin domain. The collectrin domain may regulate tissue response to injury whereas the catalytic domain is involved in peptide processing events.


Screening for beta thalassaemia and HbE traits with the mean red cell volume in pregnant women.
Both beta thalassaemia and HbE disease are microcytic red cell disorders. Pregnancy however induces macrocytosis which makes screening with the mean cell volume (MCV) difficult in antenatal patients. In addition, population screening for HbE has not been widely reported in the literature and the screening criteria for beta thalassaemia may not necessarily apply. A study of the value of the MCV for routine screening for both beta thalassaemia and HbE traits in 3696 antenatal patients of different gestational ages was carried out. All patients with an MCV < or = 80 fL received confirmatory tests for haemoglobinopathies. The MCV rose by only 2.0% in pregnancy. A total of 494 patients (13.4% of the general population) had an MCV < or = 80 fL. Of these microcytic patients, 11.3% (56) and 4.7% (23) were eventually confirmed to have beta thalassaemia and HbE traits respectively. The mean MCV for the 3696 antenatal patients was 87.8 fL (SD 7.5) compared to patients with beta thalassaemia and HbE traits, which were 67.5 fL (SD 4.5) and 75.7 fL (SD 4.1). HbE traits were less microcytic than beta thalassaemia traits and overlapped significantly with the general population. Beta thalassaemia trait and HbE trait detected by this screening method constituted 1.52% and 0.62% respectively of the total antenatal population screened. The MCV remains a valid screening parameter in pregnancy for beta thalassaemia trait. As for HbE trait, applying a discriminant value of 80 fL to the MCV in the population screening would miss a significant proportion of the HbE traits.(ABSTRACT TRUNCATED AT 250 WORDS)


Chronic periaortitis with antiphospholipid syndrome.
Chronic periaortitis (CP) is a rare disease, the common denominator of which is a retroperitoneal periaortic fibroinflammatory tissue that frequently obstructs neighboring structures. CP has already been reported in association with various autoimmune disorders, such as Hashimoto's thyroiditis, systemic lupus erythematosus and Sjögren's syndrome. The association with autoimmune disorders suggests that CP is a manifestation of a systemic autoimmune process. We describe the first case of antiphospholipid syndrome in a patient with CP.


Linking economics and quality: developing an evidence-based nurse staffing tool.
The evidence linking nurse staffing with patient outcomes has been established; however, incorporating the evidence into practice is lagging. This article describes a practice/academic collaborative initiated to promote the translation of staffing research into decision-making through the development of an evidence-based staffing tool. Reports of previous research on nurse staffing and patient and financial outcomes are summarized, and aspects of the 2 phases of the collaborative to date are discussed. In the initial phase, a pilot research study on nurse staffing and patient outcomes in medical-surgical units support previous findings that higher nurse staffing results in positive patient outcomes. The focus in the current phase is expansion of the pilot research and the development of a decision-making staffing tool based on the additional staffing research. Identifying the critical data elements and sources of the data are major challenges to achieving the project objectives. Other challenges are maintaining interest and creating wide-spread understanding of the importance of nurse managers having access to timely, useable information. The success of the collaborative is due to the commitment and participation of leaders from various disciplines in both organizations.


Disparities in 30-Day Rehospitalization Rates Among Medicare Skilled Nursing Facility Residents by Race and Site of Care.
To examine racial and site-of-care disparities in all-cause and potentially avoidable 30-day rehospitalization rates among a national cohort of Medicare skilled nursing facility (SNF) residents. We analyzed the 2012 Minimum Data Set, Medicare inpatient claims, and other data. Multivariable logistic regressions were used to adjust for resident demographic, functional, and diagnostic characteristics, as well as observed SNF and geographic factors. Conditional fixed effects for SNFs were further used to adjust for both observed and unobserved factors. Independent effects of black race and site-of-care groups were estimated, where sites were defined using proportions of black Medicare admissions to the SNF. The 30-day all-cause and potentially avoidable rehospitalization rates were 21.9% and 8.8%, respectively, for black residents (n=120,508), and 17.7% and 7.9% for white residents (n=1,182,003). Racial disparities persisted after adjustment for resident characteristics. Moreover, risk-adjusted disparities were essentially related to the type of SNFs to which residents were admitted; after controlling for SNF sites, significant racial disparity disappeared for potentially available rehospitalizations. Black residents and white residents admitted to SNFs with high proportions of black admissions (>25%) were 31% and 19%, respectively, more likely to be rehospitalized than white residents admitted to SNFs caring for only a small percentage of black postacute residents (<3%). Compared with white SNF residents, black SNF residents are more likely to be rehospitalized even after adjusting for patient risk factors. Black-white disparities, especially in potentially preventable rehospitalizations, are largely due to the fact that black residents tend to be admitted to the small number of SNFs with very high rehospitalization rates.


Occupational lead neurotoxicity: a behavioural and electrophysiological evaluation. Study design and year one results.
To evaluate the effects of chronic lead exposure on the nervous system in adults, a set of neurobehavioural and electrophysiological tests was administered to 99 lead exposed foundry employees and 61 unexposed workers. Current and past blood lead concentrations were used to estimate the degree of lead absorption; all previous blood lead concentrations had been less than or equal to 90 micrograms/100 ml. Characteristic signs (such as wrist extensor weakness) or symptoms (such as colic) of lead poisoning were not seen. Sensory conduction in the sural nerve was not affected. By contrast, various neurobehavioural functions deteriorated with increasing lead burden. Workers with blood lead concentrations between 40 and 60 micrograms/100 ml showed impaired performance on tests of verbal concept formation, visual/motor performance, memory, and mood. Thus impairment in central nervous system function in lead exposed adults occurred in the absence of peripheral nervous system derangement and increased in severity with increasing lead dose.


Effect of higher-order aberrations and intraocular scatter on contrast sensitivity measured with a single instrument.
Higher-order aberrations (HOAs) and intraocular scatter lead to the degradation of image quality on the retina, and consequently deteriorate subjective visual performance. In this article, we modified an adaptive optics double-pass system to combine objective and subjective visual testing capabilities. Employing the modified DP system, we investigated the effects of HOAs and intraocular scatter on contrast sensitivity. Contrast sensitivity measurements were performed with HOAs either retained or corrected by adaptive optics, and with scatter either remaining at the natural eye-induced level or further enhanced by a set of three different scatter filters. Contrast sensitivity was found to be worse when HOAs were uncorrected or scatter increased. Quantitative analysis indicated that the joint effect of HOAs and scatter on contrast sensitivity was not a simple summation of each contributing factor, suggesting a potential compensatory mechanism between HOAs and intraocular scatter on contrast sensitivity.


Far infrared radiation promotes rabbit renal proximal tubule cell proliferation and functional characteristics, and protects against cisplatin-induced nephrotoxicity.
Far infrared radiation, a subdivision of the electromagnetic spectrum, is beneficial for long-term tissue healing, anti-inflammatory effects, growth promotion, sleep modulation, acceleration of microcirculation, and pain relief. We investigated if far infrared radiation is beneficial for renal proximal tubule cell cultivation and renal tissue engineering. We observed the effects of far infrared radiation on renal proximal tubules cells, including its effects on cell proliferation, gene and protein expression, and viability. We also examined the protective effects of far infrared radiation against cisplatin, a nephrotoxic agent, using the human proximal tubule cell line HK-2. We found that daily exposure to far infrared radiation for 30 min significantly increased rabbit renal proximal tubule cell proliferation in vitro, as assessed by MTT assay. Far infrared radiation was not only beneficial to renal proximal tubule cell proliferation, it also increased the expression of ATPase Na+/K+ subunit alpha 1 and glucose transporter 1, as determined by western blotting. Using quantitative polymerase chain reaction, we found that far infrared radiation enhanced CDK5R1, GNAS, NPPB, and TEK expression. In the proximal tubule cell line HK-2, far infrared radiation protected against cisplatin-mediated nephrotoxicity by reducing apoptosis. Renal proximal tubule cell cultivation with far infrared radiation exposure resulted in better cell proliferation, significantly higher ATPase Na+/K+ subunit alpha 1 and glucose transporter 1 expression, and significantly enhanced expression of CDK5R1, GNAS, NPPB, and TEK. These results suggest that far infrared radiation improves cell proliferation and differentiation. In HK-2 cells, far infrared radiation mediated protective effects against cisplatin-induced nephrotoxicity by reducing apoptosis, as indicated by flow cytometry and caspase-3 assay.


Tuberculosis verrucosa cutis (TBVC)--foot with miliary tuberculosis.
Tuberculosis Verrucosa Cutis (TBVC) or warty tuberculosis is a variant of cutaneous tuberculosis in patients with good cell mediated immunity (CMI) to Mycobacterium Tuberculosis, while Miliary Tuberculosis is associated with very poor CMI. Two widely different clinical presentations in the same patient are very rare and being reported.


Armcx1 attenuates secondary brain injury in an experimental traumatic brain injury model in male mice by alleviating mitochondrial dysfunction and neuronal cell death.
Armcx1 is highly expressed in the brain and is located in the mitochondrial outer membrane of neurons, where it mediates mitochondrial transport. Mitochondrial transport promotes the removal of damaged mitochondria and the replenishment of healthy mitochondria, which is essential for neuronal survival after traumatic brain injury (TBI). This study investigated the role of Armcx1 and its potential regulator(s) in secondary brain injury (SBI) after TBI. An in vivo TBI model was established in male C57BL/6 mice via controlled cortical impact (CCI). Adeno-associated viruses (AAVs) with Armcx1 overexpression and knockdown were constructed and administered to mice via stereotactic cortical injection. Exogenous miR-223-3p mimic or inhibitor was transfected into cultured cortical neurons, which were then scratched to simulate TBI in vitro. It was found that Armcx1 expression decreased significantly, while miR-223-3p levels increased markedly in peri-lesion tissues after TBI. The overexpression of Armcx1 significantly reduced TBI-induced neurological dysfunction, neuronal cell death, mitochondrial dysfunction, and axonal injury, while the knockdown of Armcx1 had the opposite effect. Armcx1 was potentially a direct target of miR-223-3p. The miR-223-3p mimic obviously reduced the Armcx1 protein level, while the miR-223-3p inhibitor had the opposite effect. Finally, the miR-223-3p inhibitor dramatically improved mitochondrial membrane potential (MMP) and increased the total length of the neurites without affecting branching numbers. In summary, our results suggest that the decreased expression of Armcx1 protein in neurons after experimental TBI aggravates secondary brain injury, which may be regulated by miR-223-3p. Therefore, this study provides a potential therapeutic approach for treating TBI.


Retrospective study of gingival involvement in pemphigus: A difficult to treat phenomenon.
Pemphigus is a group of autoimmune diseases characterized by flaccid lesions on the skin and mucous membranes. In pemphigus vulgaris, the most common subtype of pemphigus, lesions might be appeared anywhere on the oral mucosa, mostly in the buccal mucosa. However, the gingiva is a less frequently affected site. Here, we performed a retrospective study at Tehran University of Medical Sciences, covering a two-year period to identify pemphigus patients with active lesions confined to the gingiva. Considering 1787 initially evaluated pemphigus cases, 512 (28.6%) were found to have a history of gingival involvement. Among them, 31 patients had only gingival involvement during their last visit, including 29 (93.5%) women and only two (6.5%) men. The mean of disease duration in this group was 5.29 ± 3.46 years, and they had gingival involvement for a mean of 23.9 ± 19.3 months. Of 28 patients, nine were negative for anti-Dsg3 and 24 were negative for anti-Dsg1. In 24 patients, who received rituximab, the mean pemphigus disease area index specifically for gingiva was 4.76 ± 0.74 at baseline, which had changed to 4.13 ± 0.75 and 3.26 ± 0.63 three and 6 months after rituximab administration, respectively. After 3 months, gingival lesions were either entirely resolved (n = 3), partially resolved (n = 11), remained unchanged (n = 2), or progressed (n = 7). Gingiva-confined presentation of lesions in pemphigus could be non-anti-Dsg1/3 dependent in some patients. Such patients do not respond well to conventional treatments and rituximab therapy. More studies on the pathogenesis of gingiva-confined presentation of pemphigus are required.


Discovery of A-770041, a src-family selective orally active lck inhibitor that prevents organ allograft rejection.
We describe the identification, SAR, and pharmacology of the src-family selective lck inhibitor A-770041 that prolongs the survival of major histocompatibility mismatched allografts in models of solid organ transplant rejection for greater than 65 days.


Carborane as a tunable tag for Ru catalysts: generating an anion-appended recyclable and robust catalyst suitable for the noncovalent binding concept.
Ruthenium carbene complexes 9 with a closo-1,2-C(2)B(10)H(11) tag and 10 with an ionic [nido-7,8-C(2)B(9)H(11)](-) tag were synthesized. Both 9 and 10 are highly reactive catalysts for olefin metathesis reactions. Importantly, 10 is a robust and recyclable anion-appended catalyst that was suitable for noncovalent binding with many cationic resins. At least ten recycles were achieved for RCM of the selected substrate using 10 as the catalyst in ionic liquids.


Phase separation behavior in aqueous suspensions of bacterial cellulose nanocrystals prepared by sulfuric acid treatment.
Phase separation phenomena of aqueous suspensions of cellulose nanocrystals have been studied for bacterial cellulose (BC) prepared by sulfuric acid hydrolysis. Suspensions at concentrations above 0.42 wt % separated into the isotropic and chiral nematic phases with a clear phase boundary. The shape and size distribution of BC nanocrystals in both the phases were determined by transmission electron microscopy (TEM) and atomic force microscopy (AFM). The surface charge density was determined by conductometric titration. The effects of added NaCl (0-5.0 mM) on the phase separation behavior of the aqueous suspensions were investigated for a fixed total cellulose concentration. The volume fraction of the chiral nematic phase had a minimum value at a NaCl concentration of ca. 1.0 mM. At NaCl concentrations ranging from 2.0 to 5.0 mM, the suspensions did not separate into two phases, but became entirely liquid crystalline. The size of the ordered domains in the anisotropic phase decreased with an increase in the NaCl concentration from 0 to 2.75 mM. At 2.75 mM, only tactoids were observed in the entire region. At 5.0 mM, chiral nematic domains were no longer observed. The chiral nematic pitch decreased with increasing concentration of added NaCl, reached a minimum value at approximately 0.75 mM, and then increased sharply with the NaCl concentration up to 2.0 mM.


Seasonal variations in the activity budget of Japanese macaques in the coniferous forest of Yakushima: effects of food and temperature.
Seasonal variations in the activity budget of Japanese macaques in the coniferous forest of Yakushima were studied over the course of 1 year. On an annual basis, they spent 38% of the daytime feeding, 16% traveling, 14% in social interactions, and 32% engaged in resting. The effects of temperature and food-related factors (i.e., food distribution, feeding speed, and food abundance) on the seasonal variations of activity budget were examined by stepwise multiple regression analysis. When the temperature was low, the macaques decreased traveling and feeding time, in accordance with the prediction that endothermal animals save energy under severe thermoregulatory cost. When the feeding speed of available foods was slow, they spent more time feeding. When high-quality foods were abundant, they decreased feeding time. These macaques did not respond to fluctuations in food distribution. The present results indicate the importance of temperature, in addition to food-related factors, as a determinant of activity budgets.


Constitutive silencing of LRRK2 kinase activity leads to early glucocerebrosidase deregulation and late impairment of autophagy in vivo.
Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease. LRRK2 modulates the autophagy-lysosome pathway (ALP), a clearance process subserving the quality control of cellular proteins and organelles. Since dysfunctional ALP might lead to α-synuclein accumulation and, hence, Parkinson's disease, LRRK2 kinase modulation of ALP, its age-dependence and relation with pSer129 α-synuclein inclusions were investigated in vivo. Striatal ALP markers were analyzed by Western blotting in 3, 12 and 20-month-old LRRK2 G2019S knock-in mice (bearing enhanced kinase activity), LRRK2 knock-out mice, LRRK2 D1994S knock-in (kinase-dead) mice and wild-type controls. The lysosomotropic agent chloroquine was used to investigate the autophagic flux in vivo. Quantitative Real-time PCR was used to quantify the transcript levels of key ALP genes. The activity of the lysosomal enzyme glucocerebrosidase was measured using enzymatic assay. Immunohistochemistry was used to co-localize LC3B puncta with pSer129 α-synuclein inclusion in striatal and nigral neurons. No genotype differences in ALP markers were observed at 3 months. Conversely, increase of LC3-I, p62, LAMP2 and GAPDH levels, decrease of p-mTOR levels and downregulation of mTOR and TFEB expression was observed in 12-month-old kinase-dead mice. The LC3-II/I ratio was reduced following administration of chloroquine, suggesting a defective autophagic flux. G2019S knock-in mice showed LAMP2 accumulation and downregulation of ALP key genes MAP1LC3B, LAMP2, mTOR, TFEB and GBA1. Subacute administration of the LRRK2 kinase inhibitor MLi-2 in wild-type and G2019S knock-in mice did not replicate the pattern of kinase-dead mice. Lysosomal glucocerebrosidase activity was increased in 3 and 12-month-old knock-out and kinase-dead mice. LC3B puncta accumulation and pSer129 α-synuclein inclusions were dissociated in striatal neurons of kinase-dead and G2019S knock-in mice. We conclude that constitutive LRRK2 kinase silencing results in early deregulation of GCase activity followed by late impairment of macroautophagy and chaperone-mediated autophagy.


Cell type-dependent axonal localization of translational regulators and mRNA in mouse peripheral olfactory neurons.
Local protein synthesis in mature axons may play a role in synaptic plasticity, axonal arborization, or functional diversity of the circuit. To gain insight into this question, we investigated the axonal localization of translational regulators and associated mRNAs in five parallel olfactory circuits, four in the main olfactory bulb and one in the accessory olfactory bulb. Axons in all four main olfactory bulb circuits exhibited axonal localization of Fragile X granules (FXGs), structures that comprise ribosomes, mRNA, and RNA binding proteins including Fragile X mental retardation protein (FMRP) and the related protein FXR2P. In contrast, FXGs were not seen in axons innervating the accessory olfactory bulb. Similarly, axons innervating the main olfactory bulb, but not the accessory olfactory bulb, contained the FXG-associated mRNA Omp (olfactory marker protein). This differential localization was not explained by circuit-dependent differences in expression of FXG components or Omp, suggesting that other factors must regulate their axonal transport. The specificity of this transport was highlighted by the absence from olfactory axons of the calmodulin transcript Calm1, which is highly expressed in peripheral olfactory neurons at levels equivalent to Omp. Regulation of axonal translation by FMRP may shape the structure and function of the axonal arbor in mature sensory neurons in the main olfactory system but not in the accessory olfactory system.


Cloning and characterisation of the mouse fra-2 gene.
Transcription factor AP-1 is comprised of multiple protein complexes that include members of a family of genes related to the proto-oncogene c-fos. In this report, we have extended the analysis of one member of this family, fos-related antigen-2 (fra-2), by isolating and characterising genomic and cDNA clones encoding the mouse fra-2 homolog. The overall gene structure (number and positions of introns) was similar to that of both the chicken fra-2 gene and other members of the fos family, and the relative positions of putative enhancers in the 5' regulatory region were well conserved between the mouse and chicken fra-2 genes. High levels of fra-2 mRNA were detected in ovary, stomach, small and large intestine, brain, lung and heart. The mouse Fra-2 protein showed 94% and 87.5% conservation with human and chicken Fra-2, respectively, and mouse Fra-2, like the chicken homolog, induced transformation of chicken embryo fibroblasts. The characterisation of the mouse fra-2 gene provides a basis for analysis of Fra-2 function in the whole animal.


Enantiomeric separation of ketoconazole and terconazole antifungals by electrokinetic chromatography: Rapid quantitative analysis of ketoconazole in pharmaceutical formulations.
EKC using a neutral CD as chiral selector was applied in this work to the development of a method enabling the enantiomeric separation of ketoconazole and terconazole antifungals. The influence of different experimental conditions such as temperature, CD concentration, pH, and nature and concentration of the buffer on the enantiomeric resolution of the compounds studied was investigated. The use of 10 mM heptakis-(2,3,6-tri-O-methyl)-beta-CD in a 100 mM phosphate buffer (pH 3.5) with a temperature of 15 degrees C allowed the separation of the enantiomers of ketoconazole and terconazole with high resolution (R(s) > 2.0). The rapid separation of ketoconazole enantiomers with an analysis time less than 3 min was carried out after fitting some experimental parameters. The developed method was applied to the determination of ketoconazole in different pharmaceutical formulations.


The clinical context of technology assessment.
One important aspect of the evaluation of a new medical technology is the clinical context in which the technology will be used. This context includes the disease to be diagnosed or treated, alternative methods of diagnosis or treatment, and the epidemiology of both the illness itself and health services. This paper presents a simple clinical paradigm of use in assessing new technologies.


Dopamine receptor D4 (DRD4) gene modulates the influence of informational masking on speech recognition.
Listeners vary substantially in their ability to recognize speech in noisy environments. Here we examined the role of genetic variation on individual differences in speech recognition in various noise backgrounds. Background noise typically varies in the levels of energetic masking (EM) and informational masking (IM) imposed on target speech. Relative to EM, release from IM is hypothesized to place greater demand on executive function to selectively attend to target speech while ignoring competing noises. Recent evidence suggests that the long allele variant in exon III of the DRD4 gene, primarily expressed in the prefrontal cortex, may be associated with enhanced selective attention to goal-relevant high-priority information even in the face of interference. We investigated the extent to which this polymorphism is associated with speech recognition in IM and EM conditions. In an unscreened adult sample (Experiment 1) and a larger screened replication sample (Experiment 2), we demonstrate that individuals with the DRD4 long variant show better recognition performance in noise conditions involving significant IM, but not in EM conditions. In Experiment 2, we also obtained neuropsychological measures to assess the underlying mechanisms. Mediation analysis revealed that this listening condition-specific advantage was mediated by enhanced executive attention/working memory capacity in individuals with the long allele variant. These findings suggest that DRD4 may contribute specifically to individual differences in speech recognition ability in noise conditions that place demands on executive function.


Ti-TiC-TiC/DLC gradient nano-composite film on a biomedical NiTi alloy.
Ti-TiC-TiC/diamond-like carbon (DLC) gradient nano-composite films have been prepared on NiTi alloy substrates by the technique of plasma immersion ion implantation and deposition (PIIID) combined with plasma-enhanced chemical vapor deposition (PECVD). The influence of negative bias voltage applied to the substrate (from -100 V to -500 V) on the chemical structure, microstructure, mechanical properties and corrosion resistance was investigated by Raman spectrum, x-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), x-ray diffraction (XRD), friction coefficient test, scratch test, nano-indentation test and anodic polarization experiments. The Raman spectrum and XPS results showed that the doped films kept an amorphous DLC structure. TEM observation revealed that nanometer TiC particles were surrounded by the amorphous DLC. With the increase of bias voltage, the ratio of sp(2)/sp(3) first decreased, reaching a minimum value at -200 V, and then increased. The nano-indentation results showed that the hardness of the Ti-TiC-TiC/DLC gradient films reached the maximum value at -200 V when TiC particles reached the maximum content in the films. The friction coefficient test and scratch test indicated that Ti-TiC-TiC/DLC gradient films had a low friction coefficient and high bonding strength with the NiTi substrates. Combined with anodic polarization curves and SEM observation, it was found that the corrosion resistance of the Ti-TiC-TiC/DLC gradient films was much better than that of the bare NiTi alloy.


Cognitive operations in the generation effect on a recall test: role of aging and divided attention.
Generation effect (generated words are better memorized than read words) of anagrams, rhymes, and associates of target words was examined in young, elderly, and very old subjects. Experiments 1 and 2 showed that only young subjects benefit from the generation effect in a free-recall test when the rule is of a phonological nature. Experiments 3, 4, and 5 showed that the generation effect of rhymes was due to a resources-dependent self-initiated process. Experiments 4 and 5 showed that in a divided-attention situation, generation effect of rhymes is not significant in young subjects, but that the generation effect of semantic associates remains significant for both groups (Experiment 5). The results are discussed within the environmental support framework and the transfer-appropriate processing framework.


Effective Parameters for Gait Analysis in Experimental Models for Evaluating Peripheral Nerve Injuries in Rats.
Chronic constriction injury (CCI) of the sciatic nerve is a peripheral nerve injury widely used to induce mononeuropathy. This study used machine learning methods to identify the best gait analysis parameters for evaluating peripheral nerve injuries. Twenty-eight male Wistar rats (weighing 270±10 g), were used in the present study and divided into the following 4 groups: CCI with 4 ligatures around the sciatic nerve (CCI-4L; n=7), a modified CCI model with 1 ligature (CCI-1L; n=7), a sham group (n=7), and a healthy control group (n=7). All rats underwent gait analysis 7 and 28 days postinjury. The data were evaluated using Kinovea and WeKa software (machine learning and neural networks). In the machine learning analysis of the experimental groups, the pre-swing (PS) angle showed the highest ranking in all 3 analyses (sensitivity, specificity, and area under the receiver operating characteristics curve using the Naive Bayes, k-nearest neighbors, radial basis function classifiers). Initial contact (IC), step length, and stride length also performed well. Between 7 and 28 days after injury, there was an increase in the total course time, step length, stride length, stride speed, and IC, and a reduction in PS and IC-PS. Statistically significant differences were found between the control group and experimental groups for all parameters except speed. Interactions between time after injury and nerve injury type were only observed for IC, PS, and IC-PS. PS angle of the ankle was the best gait parameter for differentiating nonlesions from nerve injuries and different levels of injury.


[Perinatal herpes simplex infection].
Neonatal herpes is a rare disease which has to be distinguished from herpes simplex virus infection later on in life. Most neonates in whom HSV infection develops have acquired the virus from the maternal genital tract during delivery. Clinical symptoms and prophylactic measures are discussed. Antiviral therapy with acyclovir is the treatment of choice and appears to improve outcome of neonatal herpes. The prognosis depends on early therapy, but the available diagnostic techniques not always allow early detection of the disease. Therefore treatment should be initiated in relation to clinical findings.


Anticoagulation in chronic thromboembolic pulmonary hypertension: A systematic review and meta-analysis.
Life-long anticoagulation is the recommended management for chronic thromboembolic pulmonary hypertension (CTEPH). Evidence regarding the use of direct oral anticoagulants (DOAC) for CTEPH is yet to be established. We performed a systematic review and meta-analysis to clarify the outcomes of CTEPH in patients who used DOAC or vitamin K antagonists (VKA). We reviewed literature in PubMed and EMBASE through March 2023. We included studies involving patients with CTEPH where DOAC and VKA were compared. We collected data including intervention history for CTEPH, bleeding events, recurrence of VTE (venous thromboembolism), and mortality. We performed a meta-analysis using the Mantel-Haenszel method with a fixed-effects model. We included one randomized clinical trial and six observational studies, with a total of 2969 patients. Six studies investigated major bleeding outcomes, and seven investigated all bleeding outcomes. There were no differences in major bleeding (RR 0.59, 95 % CI [0.34-1.02], I2 = 0 %) and all-bleeding (RR 0.87, 95 % CI [0.67-1.13], I2 = 0 %). Based on the five studies we included, DOAC was associated with a lower risk of mortality (RR 0.54, 95 % CI: 0.37-0.79, I2 = 5 %). However, a higher risk of recurrent pulmonary embolism (PE) was seen in three studies (RR 3.80, 95 % CI: [1.93-7.50], I2 = 11 %). No significant differences were noted in terms of VTE. DOAC compared to VKA was associated with a significantly lower mortality and higher risk of recurrent PE. Since most of the included studies are observational, we must consider the existence of multiple biases and confounding factors.


[Partial ejaculatory duct obstruction induces hemospermia syndrome in the rat model].
To investigate the pathogenesis of hematospermia syndrome using the rat model of hemospermia induced by partial ejaculatory duct obstruction. Fifty male rats were divided into Groups A (n=20) and B (n=30), the former subjected to incomplete ligation of the right ejaculatory duct, while the latter open-close sham operation. Electro-stimulation was performed for ejaculation induction one week after the operation. Those that developed hematospermia in Group A were chosen as Group A1, while those with normal ejaculation in Group B included in Group B1. The semen indexes and seminal vesicle pressure were compared between Groups A1 and B1. Compared with Group B1, Group A1 showed significantly decreased semen volume (P < 0.01), lower sperm motility (P < 0.01) and higher seminal vesicle pressure (P < 0.01), but no statistically significant differences were observed in the WBC count and sperm density in the semen between the two groups (P > 0.05). Hemospermia syndrome can be induced by partial ejaculatory duct obstruction, with changes of semen indexes, and it is closely correlated with high seminal vesicle pressure.


cAMP-associated inhibition of Na+-H+ exchanger in rabbit kidney brush-border membranes.
Adenosine 3',5'-cyclic monophosphate (cAMP) inhibits the rate of bicarbonate reabsorption and the rate of Na+-H+ exchange transport in the apical membrane of the proximal convoluted tubule. To study the relation between cAMP, cAMP-dependent protein kinase, and Na+-H+ exchange transport, brush-border membrane vesicles from the rabbit kidney were phosphorylated in vitro. The rate of proton gradient-stimulated amiloride-inhibitable 22Na+ uptake was measured as an index of Na+-H+ exchange transport activity. The inclusion of cAMP (10(-6) M) in a phosphorylating solution containing ATP decreased the 10-s uptake of amiloride-sensitive sodium from 2.25 +/- 0.21 nmol/mg protein in controls to 1.94 +/- 0.19 (P less than 0.001). Incubation of vesicles in the presence of purified catalytic subunit of cAMP-dependent protein kinase inhibited the amiloride-sensitive uptake of 22Na+ at 10 s from 2.35 +/- 0.49 nmol/mg protein to 2.05 +/- 0.44 (P less than 0.005). The inhibitory effect of both cAMP and catalytic subunit of cAMP-dependent protein kinase was blocked by the specific thermostable protein inhibitor of the kinase. These studies demonstrate that activation of endogenous membrane-bound cAMP-dependent protein kinase or exposure to exogenous catalytic subunit of cAMP-dependent protein kinase inhibits the rate of Na+-H+ exchange transport in the brush-border membrane of the rabbit kidney.


Fabrication of an optical lens array using ultraviolet light and ultrasonication.
A technique to form an optical lens array using an ultraviolet (UV)-curable resin and ultrasound was investigated. A UV-curable gel film was formed on a glass plate having four lead zirconate titanate (PZT) transducers. Excitation of the transducers generated a lattice flexural vibration mode on the glass plate. The acoustic radiation force acted to deform the surface of the gel film, so that a lens array could be fabricated on the gel film. The lens array was exposed to UV light under ultrasonication to cure the UV-curable film. The quality factor of the transducer resonance was decreased upon curing of the resin film because the cured resin dampened the vibration of the plate. The acoustic characteristics of the UV-curable gel film were measured by using an ultrasound pulse technique at the MHz range. The sound speed of the gel increased from 987 to 1006 m/s (increase of 1.9%) as the UV exposure time increased. The attenuation coefficient also increased and the larger attenuation of the resin caused the lens array to have a lower quality factor.


[Rett syndrome: the state of research, and future perspectives].
Rett syndrome (RTT) is a neurodevelopmental disorder characterized by normal early psychomotor development followed by the loss of psychomotor and acquired purposeful hand skills and the onset of stereotyped movement of the hands and gait disturbance. The causative gene was discovered, and the disease was found to be caused by a mutation of methyl-CpG-binding protein 2. However, in many ways this clinically peculiar condition remains a mystery. I review the current status of clinical and basic research on RTT including data on the neurophysiology of the disease, neurotransmitter involvement, neuroimaging and neuropathology findings, molecular biology, animal models, regenerative medicine including ES cells and iPS cells, and other interventions and therapeutic trials.


Individualization of therapy using Mammaprint: from development to the MINDACT Trial.
To date, most treatment decisions for adjuvant chemotherapy in breast cancer are sed on conventional clinicopathological criteria. Since breast cancer tumors with similar clinicopathological characteristics can have strikingly different outcomes, the current selection for adjuvant chemotherapy is far from accurate. Using high-throughput microarray analysis, a 70-gene signature was identified which can accurately select early stage breast cancer patients who are highly likely to develop distant metastases, and therefore, may benefit the most from adjuvant chemotherapy. This review describes the development of the 70-gene profile (Mammaprint), its retrospective validation and feasibility studies, and its prospective validation in the large adjuvant MINDACT (Microarray In Node-negative Disease may Avoid ChemoTherapy) clinical trial.


Chronic administration of therapeutic levels of clenbuterol acts as a repartitioning agent.
The purpose of this study was to examine the effect of therapeutic levels of clenbuterol, with and without exercise training, on body composition. Twenty-three unfit Standardbred mares were divided into four experimental groups: clenbuterol (2.4 microg/kg body wt twice daily) plus exercise (ClenEx; 20 min at 50% maximal oxygen consumption 3 days/wk; n = 6), clenbuterol only (Clen; n = 6), exercise only (Ex; n = 5), and control (Con; n = 6). Rump fat thickness was measured at 2-wk intervals by using B-mode ultrasound, and percent body fat (%fat) was calculated by using previously published methods. For Ex, body fat decreased (P < 0.05) at week 4 (-9.3%), %fat at week 6 (-6.9%), and fat-free mass (FFM) increased (P < 0.05) at week 8 (+3.2%). On the other hand, Clen had significant changes in %fat (-15.4%), fat mass (-14.7%), and FFM (+4.3%) at week 2. ClenEx had significant decreases in %fat (-17.6%) and fat mass (-19.5%) at week 2, which was similar to Clen; however, this group had a different FFM response, which significantly increased (+4.4%) at week 6. Con showed no changes (P > 0.05) in any variable at any time. These results suggest that exercise training and clenbuterol have additive effects with respect to %fat and fat mass but antagonistic effects in terms of FFM. Furthermore, chronic clenbuterol administration causes significant repartitioning in the horse, even when administered in therapeutic doses.


Resistance to activated protein C and digital thrombosis.
Resistance to activated protein C is a newly described genetic coagulation disorder previously only reported in patients with venous thromboembolism or central arterial embolism (cerebral or coronary). We report this defect in association with digital artery thrombosis and describe the pathophysiology of this disorder.


Efficacy of Listerine antiseptic against MRSA, Candida albicans and HIV.
The antiseptic activity of Listerine and Cool Mint Listerine against methicillin-resistant Staphylococcus aureus (MRSA), Candida albicans, human immuno deficiency virus (HIV) and oral bacteria was examined in this study. Exposure for 30 seconds to Listerine killed MRSA completely. Exposure for 30 seconds significantly decreased viable cells of C. albicans. More than 60% of HIV was inactivated by a 30 second exposure to 50% Listerine. Listerine exhibited a potent bactericidal effect against cariogenic and periodontopathic bacteria. Cool Mint Listerine had almost the same antiseptic effect against tested microorganisms. Listerine appears to be effective for killing etiologic microorganisms of opportunistic infection in the oral cavity.


Improving immunotherapy for colorectal cancer using dendritic cells combined with anti-programmed death-ligand in vitro.
Monoclonal antibodies recognizing programmed death-ligand 1 (PD-L1) have been used for the clinical treatment of diverse tumor types as a form of immune checkpoint inhibitor, with a favorable therapeutic effect. Dendritic cells (DCs) are potent antigen-presenting cells that serve a pivotal role in the activation of T cells, particularly cytotoxic T lymphocytes (CTLs). DC vaccines loaded with tumor antigens, DC-CTLs and activated T cells have been revealed to be a safe and effective treatment approach against colorectal cancer within a clinical setting. In addition to tumor cells, PD-L1 is also highly expressed on DCs. As research examining the association between anti-PD-L1 and DCs is lacking, the present study compared the expression of PD-L1 on DCs in the peripheral blood of healthy donors and patients with colorectal cancer. Following the application of anti-PD-L1, the DC phenotypes, function of DC-mediated T cell induction and the cytotoxicity of CTLs were investigated by flow cytometry. The present study revealed that treatment with anti-PD-L1 may promote the maturation of DCs and enhance the functionality of the DC1 subtype. It may also increase the number of CTLs that are activated and produce CTL cells with more potent anti-tumor activity. Therefore, the creation of DC vaccines in conjunction with anti-PD-L1 may be an effective future treatment strategy for patients with colorectal cancer.


Mental health and quality of life in pre- and early adolescents: a school-based study in two contrasting urban areas.
To estimate the prevalence of mental health problems and to assess the quality of life in pre- and early adolescents living in two contrasting urban areas in Brazil, as well as to identify the impact of demographic factors on mental health, quality of life and school performance. Using school samples, the Strength and Difficulties Questionnaire and the Quality of Life Inventory were administered to 424 (52%) boys and 387 (48%) girls (mean age 12.6+/-1.3 years) in better-off central and poorer outer-city areas. In the total sample, the prevalence of probable psychiatric cases was 10.1% (n=77). There were no significant differences in the overall prevalence of behavior problems or global quality of life between central and outer-city areas. However, boys from the outer-city had a higher prevalence of conduct problems (12% vs. 6.2%, p=0.04), although girls did not differ significantly on any measure. In general, factors associated with poorer mental health were: having no religion, divorced parents, and being male. Living in the poorer outer-city was not associated with worse mental health or quality of life in this sample. This is in contrast with the findings of some other studies, and possible protective factors such as female gender and religion are discussed.


Rapid and sensitive one-tube detection of mpox virus using RPA-coupled CRISPR-Cas12 assay.
Mpox is caused by a zoonotic virus belonging to the Orthopoxvirus genus and the Poxviridae family. In this study, we develop a recombinase polymerase amplification (RPA)-coupled CRISPR-Cas12a detection assay for the mpox virus. We design and test a series of CRISPR-derived RNAs(crRNAs) targeting the conserved D6R and E9L genes for orthopoxvirus and the unique N3R and N4R genes for mpox viruses. D6R crRNA-1 exhibits the most robust activity in detecting orthopoxviruses, and N4R crRNA-2 is able to distinguish the mpox virus from other orthopoxviruses. The Cas12a/crRNA assay alone presents a detection limit of 108 copies of viral DNA, whereas coupling RPA increases the detection limit to 1-10 copies. The one-tube RPA-Cas12a assay can, therefore, detect viral DNA as low as 1 copy within 30 min and holds the promise of providing point-of-care detection for mpox viral infection.


Recommendations for implementing policy, systems, and environmental improvements to address chronic diseases in Asian Americans, Native Hawaiians, and Pacific Islanders.
Emphasis has increased recently on disseminating high-impact, population-wide strategies for the prevention of chronic diseases. However, such strategies are typically not effective at reaching Asian Americans, Native Hawaiians, Pacific Islanders, or other underserved communities. The objectives of this article were to 1) present the methods of the Strategies to Reach and Implement the Vision of Health Equity program in which 15 community-based organizations in the United States and the Pacific region implemented evidence-based policy, systems, and environmental improvements in their local communities and 2) provide recommendations for using these tailored approaches in other communities and geographic locations. Further support is needed for organizations in tailoring these types of population-wide strategies. Implementing population health improvements should be adapted to maximize effectiveness to decrease chronic diseases in these populations and ultimately eliminate racial/ethnic health disparities.


Computer as Aid in Describing Form in Gastropod Shells.
The basic form of many coiled gastropod shells can be defined by four parameters. A digital computer with automatic plotting equipment can be used to make graphical reconstructions of a shell from any given values of the four parameters.


Determination of volatility of ionic liquids at the nanoscale by means of ultra-fast scanning calorimetry.
The determination of vaporization enthalpies of extremely low volatility ionic liquids is challenging and time consuming due to the low values of vapor pressure. In addition, these liquids tend to decompose even at temperatures where the vapor pressure is still low. Conventional methods for determination of vaporization enthalpies are thus limited to temperatures below the decomposition temperature. Here we present a new method for the determination of vaporization enthalpies of such liquids using differential fast scanning calorimetry. We have developed and proven this method using [EMIm][NTf2] at temperatures of up to 750 K and in different atmospheres. It was demonstrated that evaporation is still the dominating process of mass loss even at such highly elevated temperatures. In addition, since the method allows very high heating rates (up to 10(5) K s(-1)), much higher temperatures can be reached in the measurement of the mass loss rate as compared to common devices without significant decomposition of the ionic liquid. We discuss the advantages and limits of this new method of vaporization enthalpy determination and compare the results with data obtained from established methods.


Selective repression of actin and myosin heavy chain expression during the programmed death of insect skeletal muscle.
The intersegmental muscles (ISMs) of the tobacco hawkmoth Manduca sexta undergo two sequential changes in mass at the end of metamorphosis. Atrophy results in a 40% loss of muscle mass beginning 3 days before adult eclosion (emergence). Coincident with eclosion, the ISMs undergo programmed cell death that results in the complete destruction of the muscles during the subsequent 30 hr. These developmental changes are initiated by sequential decreases in the circulating titer of the ecdysteroids. While the molecular basis of ISM atrophy is largely unknown, the commitment of the muscles to die has been shown to require the repression of specific genes and the activation of others. Data presented here suggest that two of the repressed genes encode the proteins actin and myosin heavy chain. Expression of both actin and myosin heavy chain mRNA was greatly decreased when the ISMs became committed to die. When animals were treated with 20-hydroxyecdysone, cell death was delayed and the loss of these transcripts was reduced. At the protein level, actin expression was reduced by 84% at the time the muscles were committed to die. The reduction in actin and myosin heavy chain synthesis presumably plays a role in the rapid dissolution of the muscles.


Prevention Mechanism of 2,3,5,4'-Tetrahydroxy-stilbene-2-O-β-D-glucoside on Lipid Accumulation in Steatosis Hepatic L-02 Cell.
2,3,5,4'-Tetrahydroxy-stilbene-2-O-β-d-glucoside (TSG), a natural stilbene, shows great activities in hepatic lipid regulation, especially for hepatic triglyceride lowering. However, information about its mechanisms on biosynthesis and degradation of triglyceride is still limited. This research pays close attention to clarify the mechanism of TSG on prevention of hepatic lipid accumulation. TSG was given to steatosis hepatocyte L-02 cell induced by fat emulsion incubation. The contents of free fatty acid, triglyceride, rate-controlling enzymes, and transcriptional regulatory factors, which play key role in biosynthesis and decomposition of triglyceride, were determined with or without TSG exposure. TSG could reduce the free fatty acid material supply for the synthesis of endogenous triglyceride and it did so by reducing the expression of liver type fatty acid binding protein and fatty acid transport protein 4. TS Ginhibited the expression of sterol regulatory element-binding protein 1c, and then reduce the contents of acetyl-CoA carboxylase 1 and fatty acid synthase. Therefore, TSG prevented biosynthesis of triglyceride. Mean while, TSG also promoted the decomposition of triglyceride by the activation of peroxisome proliferators activator receptors alpha. TSG could effective intervene the accumulation of triglyceride in hepatic cell. Thus, TSG could be considered as a promising drug candidate in prevention and treatment of lipid metabolic disorders, especially nonalcoholic fatty liver disease. Abbreviations Used: ACACA: Acetyl-CoA carboxylase 1, Apo-B100: Apo lipoprotein B100, FASN: Fatty acid synthase, FATP4: Fatty acid transport protein 4, FBS: Fetal bovine serum; FEN: Fenofibrate, FFA: Free fatty acid, L-FABP: Liver type fatty acid binding protein, LPL: Lipoprotein lipase, MTTP: Microsomal triglyceride transfer protein, NAFLD: Non-alcoholic fatty liver disease, PBS: Phosphate buffer saline, PPAR-α: Peroxisome proliferators activator receptors alpha, RPMI: Roswell Park Memorial Institute, SIM: Simvastatin, SREBF1c: Sterol regulatory element-binding protein 1c, TG: Triglyceride, TSG: 2, 3, 5, 4-tetrahydroxy-stilbene-2-O-β-Dglucoside, VLDL: Very low density lipoprotein.


Awake/sleep cortisol levels and the development of posttraumatic stress disorder in injury patients with peritraumatic dissociation.
Differences in the time of day that cortisol is sampled and failure to consider the impact of peritraumatic dissociation have been hypothesized as factors possibly contributing to the inconsistent findings in research examining associations between cortisol levels soon after trauma exposure and the subsequent development of posttraumatic stress disorder (PTSD). The present study examined associations between urinary cortisol levels during wake and sleep times soon after a serious injury and the subsequent development of PTSD in adult patients reporting low or high peritraumatic dissociative (PD) symptoms. Thirty-nine injury patients (20 with high and 19 with low PD symptoms) provided a 15-hour (6 PM to 9 AM) urine sample at 3-weeks post-injury and completed the Clinician Administered PTSD Scale at a 7-week follow-up. Participants collected their urine during wake and sleep times separately. Results showed that in the total sample and in the high PD group, wake, but not sleep, cortisol levels were lower in patients who developed PTSD compared to those who did not. A multiple linear regression analysis revealed a significant main effect of PD and a non-significant interaction between wake cortisol and PD in predicting PTSD symptom severity. In addition, results showed that PD was a better predictor of PTSD symptom severity than wake cortisol levels. These results were consistent with prior research indicating lower afternoon/evening cortisol levels in PTSD and strong associations between PD and PTSD, but did not support the existence of subgroups of PTSD patients (dissociators versus non-dissociators) who may differ in basal cortisol levels.


Reactivation of silenced genes and transcriptional therapy.
The purpose of this review is to discuss the potential role of "transcriptional therapy" to modulate the expression of target genes in order to treat monogenic as well as multifactorial disorders. In vitro and in vivo experiments with DNA demethylating and histone hyperacetylating drugs are currently performed in several laboratories on a variety of genes. In attempting to place these results into perspective, we divided the target genes into four major categories: (1) single genes with a hypermethylated CpG island; (2) single genes without a CpG island; (3) groups of genes silenced by aberrant DNA methylation; and (4) groups of genes silenced by lack of histone acetylation. We discuss the latest advances in the field of chromatin regulation and, in particular, the role of histone methylation and that of RNA interference in gene silencing. We can expect that in the future regulation of transcription will become an effective treatment for several genetic conditions.


UniPrimer: A Web-Based Primer Design Tool for Comparative Analyses of Primate Genomes.
Whole genome sequences of various primates have been released due to advanced DNA-sequencing technology. A combination of computational data mining and the polymerase chain reaction (PCR) assay to validate the data is an excellent method for conducting comparative genomics. Thus, designing primers for PCR is an essential procedure for a comparative analysis of primate genomes. Here, we developed and introduced UniPrimer for use in those studies. UniPrimer is a web-based tool that designs PCR- and DNA-sequencing primers. It compares the sequences from six different primates (human, chimpanzee, gorilla, orangutan, gibbon, and rhesus macaque) and designs primers on the conserved region across species. UniPrimer is linked to RepeatMasker, Primer3Plus, and OligoCalc softwares to produce primers with high accuracy and UCSC In-Silico PCR to confirm whether the designed primers work. To test the performance of UniPrimer, we designed primers on sample sequences using UniPrimer and manually designed primers for the same sequences. The comparison of the two processes showed that UniPrimer was more effective than manual work in terms of saving time and reducing errors.


Attenuation of nerve growth factor-induced visceral hyperalgesia via cannabinoid CB(1) and CB(2)-like receptors.
Cannabinoids have previously been shown to possess analgesic properties in a model of visceral hyperalgesia in which the neurotrophin, nerve growth factor (NGF), plays a pivotal role. The purpose of this study was to investigate the antihyperalgesic effects of two cannabinoids in NGF-evoked visceral hyperalgesia in order to test the hypothesis that endocannabinoids may modulate the NGF-driven elements of inflammatory hyperalgesia. Intra-vesical installation of NGF replicates many features of visceral hyperalgesia, including a bladder hyper-reflexia and increased expression of the immediate early gene c fos in the spinal cord. We investigated the action of anandamide and palmitoylethanolamide (PEA) on these parameters. Both anandamide (at a dose of 25 mg/kg) and PEA (at a dose of 2.5 mg/kg) attenuated the bladder hyper-reflexia induced by intra-vesical NGF. The use of cannabinoid CB1 receptor (SR141617A) and CB2 receptor (SR144528) antagonists suggested that the effect of anandamide was mediated by both CB1 and CB2 cannabinoid receptors whilst the action of PEA was via CB2 (or CB2-like) receptors only. Furthermore, anandamide (25 mg/kg) and PEA (2.5 mg/kg) reduced intra-vesical NGF-evoked spinal cord Fos expression at the appropriate level (L6) by 35 and 43%, respectively. However, neither CB1 nor CB2 receptor antagonists altered the action of anandamide. PEA-induced reduction in Fos expression was abrogated by SR144528. These data add to the growing evidence of a therapeutic potential for cannabinoids, and support the hypothesis that the endogenous cannabinoid system modulates the NGF-mediated components of inflammatory processes.


Translating genomic discoveries to the clinic in pediatric oncology.
The present study describes the recent advances in the identification of targetable genomic alterations in pediatric cancers, along with the progress and associated challenges in translating these findings into therapeutic benefit. Each field within pediatric cancer has rapidly and comprehensively begun to define genomic targets in tumors that potentially can improve the clinical outcome of patients, including hematologic malignancies (leukemia and lymphoma), solid malignancies (neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), and brain tumors (gliomas, ependymomas, and medulloblastomas). Although each tumor has specific and sometimes overlapping genomic targets, the translation to the clinic of new targeted trials and precision medicine protocols is still in its infancy. The first clinical tumor profiling studies in pediatric oncology have demonstrated feasibility and patient enthusiasm for the personalized medicine paradigm, but have yet to demonstrate clinical utility. Complexities influencing implementation include rapidly evolving sequencing technologies, tumor heterogeneity, and lack of access to targeted therapies. The return of incidental findings from the germline also remains a challenge, with evolving policy statements and accepted standards. The translation of genomic discoveries to the clinic in pediatric oncology continues to move forward at a brisk pace. Early adoption of genomics for tumor classification, risk stratification, and initial trials of targeted therapeutic agents has led to powerful results. As our experience grows in the integration of genomic and clinical medicine, the outcome for children with cancer should continue to improve.


[Surveillance and risk assessment system of schistosomiasis in Jiangsu Province Ⅲ Risk of schistosomiasis transmission in the area along the Yangtze River in Yangzhou City].
To evaluate the potential risk of schistosomiasis transmission in the area along the Yangtze River in Yangzhou City, so as to provide evidences for establishing a post-transmission surveillance system for schistosomiasis in marshland regions. The water infectivity, floating boatmen and fishermen infection, reservoir host infection and wild feces contamination were investigated in five districts/counties along the Yangtze River in Yangzhou City, including Guangling, Hanjiang, Jiangdu, Yizheng and Development Zone, and the transmission factors and risky characteristics were assessed after interruption of schistosomiasis transmission in marshland regions. A total of 15 key water regions were identified in the area along the Yangtze River in Yangzhou City in 2015. A total of 1 500 sentinel mice were placed, after breeding, their overall survival rate was 99.33%; 1 490 were dissected, with no schistosome infection. Of the 5 576 floating boatmen and fishermen examined, no schistosome infection was observed, and among the 3 566 domestic animals (including 171 cattle, 1 895 sheep and 1 500 pigs), no infections were detected. During the period between January and March, 2016, there were 3 200 mouse traps placed on 8 marshlands, and 62 wild mice were captured from 6 marshlands, with a capture rate of 1.94%, and no schistosomeinfected wild mice were seen. In addition, there were 35 pieces of fresh wild feces captured from 7 marshlands, including 11 pieces of bovine feces (31.43%), 17 pieces of sheep feces (48.57%), 2 pieces of dog feces (5.71%) and 5 pieces of other feces (14.29%), and no infections were detected. There is a low risk of schistosomiasis transmission in the area along the Yangtze River in Yangzhou City. However, the contamination of feces from bovine and sheep that are freely pastured on marshlands is a big threat to schistosomiasis control.


Low-grade disease activity in early life precedes childhood asthma and allergy.
Asthma and allergies are today the most common chronic diseases in children and the leading causes of school absences, chronic medication usage, emergency department visits and hospitalizations, which affect all members of the family and represent a significant societal and scientific challenge. These highly prevalent disorders are thought to originate from immune distortion in early childhood, but the etiology and heterogeneity of the disease mechanisms are not understood, which hampers preventive initiatives and makes treatment inadequate. The objective of this thesis is to investigate the presence of an early life disease activity prior to clinical symptoms to understand the anteceding pathophysiological steps towards childhood asthma and allergy. The thesis is built on seven studies from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000) birth cohort examining biomarkers of disease activity in 411 asymptomatic neonates in cord blood (I-II), urine (III), exhaled breath (IV-V) and infant lung function (VI-VII) in relation to the subsequent development of asthma and allergy during the first seven years of life. In papers I-II, we studied cord blood chemokines and 25(OH)-vitamin D, which represent a proxy of the inborn immature immune system, the intrauterine milieu, and the maternal immune health during pregnancy. High levels of the Th2-related chemokine CCL22 and high CCL22/CXCL11 ratio were positively correlated with total IgE level during preschool age (II). This suggests an inborn Th2 skewing of the immune system in healthy newborns subsequently developing elevated total IgE antibodies, which is considered to increase the risk of asthma and allergies later in life. Additionally, deficient cord blood 25(OH)-vitamin D levels were associated with a 2.7-fold increased risk of recurrent wheeze at age 0-7 years (I). Together, these findings support the concept that early life immune programming in the pre-symptomatic era plays an essential role for promotion of or protection against asthma and allergies. Therefore, preventive initiatives to restore immune health, such as vitamin D supplementation, should be directed to the fetus and the earliest postnatal life. The eosinophil granulocyte has a major role in the allergic inflammatory cascade and eosinophilia is considered a hallmark of many allergic phenotypes. In paper III, we examined neonatal urinary biomarkers including eosinophil protein X (u-EPX), which is contained in the eosinophil granules. Elevated u-EPX in asymptomatic neonates was associated with development of allergic sensitization and nasal eosinophilia, but not with wheezing or asthma (III). These findings suggest the presence of an ongoing low-grade disease process in early life characterized by eosinophil activation prior to appearance of allergy-related conditions. In papers IV-V, we investigated perinatal and genetic predictors of neonatal fractional exhaled nitric oxide (FeNO) and the relationship between neonatal FeNO and wheezing later in child-hood. The a priori selected determinants encompassed asthma genetic risk variants, anthropometrics, demographics, socioeconomics, parental asthma and allergy, maternal smoking, paracetamol and antibiotic usage during pregnancy, and neonatal bacterial airway colonization. Among those, only the DENND1B risk allele and paternal history of asthma and allergy were associated with increased FeNO values (V) suggesting that raised FeNO in neonatal life is primarily an inherited trait. The neonatal FeNO levels were widely dispersed (1-67 ppb) and children with values in the upper quartile were at increased risk of recurrent wheezing in early childhood, but not persistent wheezing, reduced lung function or allergy-related endpoints (IV). This suggests that elevated neonatal FeNO represents an early asymptomatic low-grade disease process other than congenitally small airway calibre contributing to a transient wheezing phenotype. Reduced lung function in neonates is associated with wheezing and asthma proneness, but it is unknown if such host factor also confers a risk of acute bronchiolitis, which is considered an index event of asthma persisting into school age. In paper VI, we investigated neonatal forced flow, volume, and responsiveness to methacholine in relation to occurrence of acute severe bronchiolitis at age 0-2 years. Children developing bronchiolitis had a 2.5-fold increased bronchial responsiveness as neonates (VI) suggesting a preexisting joint propensity of the airways to react adversely to common respiratory viruses and to develop asthma. This finding proposes airway hyperresponsiveness as yet another marker of low-grade disease activity among asymptomatic neonates on a trajectory towards childhood asthma. In paper VII, we examined whether neonates with impaired pulmonary capacity also had signs of systemic inflammation prior to clinical symptoms. Reduced FEV0.5 was significantly associated with elevated serum hs-CRP and other blood inflammatory markers (VII) suggesting presence of systemic low-grade inflammation from the beginning of life. Chronic low-grade inflammation is a common nominator of virtually all the major non-communicable welfare diseases (NCDs) of modernity whereof asthma and allergies are the earliest debuting disorders. The novel finding of systemic low-grade inflammation among neonates at increased risk of asthma and allergy, therefore implies that exploring the origins of asthma and allergy may also unravel disease mechanisms involved in other NCDs. In conclusion, the series of papers presented in this thesis (I-VII) evidence the presence of a pre-symptomatic disease process measurable in several body compartments, which supports the notion of low-grade disease activity in early life as a generic trait among neonates developing asthma and allergy. This hypothesis piggybacking on single biomarker assessments could be enforced and refined by applying novel global omics approaches. In particular, metabolomic analyses of serum, urine, and airway lining fluid from neonates as well as neonatal VOC profiling of exhaled breath may facilitate a broader understanding of the early low-grade disease activity preceding clinical symptoms. Disentangling the introductory pathophysiological mechanisms and underlying endotypes of disease is paramount for generating successful preventive measures to alleviate the major global burden of asthma, allergy, and other NCDs of modern time.


Paroxetine treatment of mood disorders in women: premenstrual dysphoric disorder and hot flashes.
With the relatively recent introduction of the selective serotonin reuptake inhibitor (SSRI) class of antidepressants, increased attention has been focused on the use of antidepressants in the treatment of mood disorders across the female life cycle. Evidence for the efficacy of antidepressants in the treatment of premenstrual dysphoric disorder (PMDD) and hot flashes associated with menopause and breast cancer has emerged. The clinical trials experience with paroxetine and the controlled-release (CR) formulation of paroxetine is reviewed.


Structural basis for targeting the ribosomal protein S1 of Mycobacterium tuberculosis by pyrazinamide.
Pyrazinamide (PZA) is a first-line drug for tuberculosis (TB) treatment and is responsible for shortening the duration of TB therapy. The mode of action of PZA remains elusive. RpsA, the ribosomal protein S1 of Mycobacterium tuberculosis (Mtb), was recently identified as a target of PZA based on its binding activity to pyrazinoic acid (POA), the active form of PZA. POA binding to RpsA led to the inhibition of trans-translation. However, the nature of the RpsA-POA interaction remains unknown. Key questions include why POA exhibits an exquisite specificity to RpsA of Mtb and how RpsA mutations confer PZA resistance. Here, we report the crystal structures of the C-terminal domain of RpsA of Mtb and its complex with POA, as well as the corresponding domains of two RpsA variants that are associated with PZA resistance. Structural analysis reveals that POA binds to RpsA through hydrogen bonds and hydrophobic interactions, mediated mainly by residues (Lys303, Phe307, Phe310 and Arg357) that are essential for tmRNA binding. Conformational changes induced by mutation or sequence variation at the C-terminus of RpsA abolish the POA binding activity. Our findings provide insights into the mode of action of PZA and molecular basis of PZA resistance associated with RpsA mutations.


Comparison of measurement methods for quantifying hand force.
Hand force is a known risk factor for upper extremity disorders. The objective of the present study was to determine the characteristics of, and the relationships between, exposure assessment methods to quantify hand force. Five methods, used in the laboratory or the field, were used to quantify hand force at three force magnitudes: two direct (or technical) measurement methods, force transducers and electromyography; an observational method; and two self-report approaches, force matching and a visual analogue scale. Five tasks, simulating manual work activities, were performed by 20 participants. The coefficients of variation of measures within and between participants were moderate. All approaches clearly distinguished between the three force levels tested. The reliability of the methods ranged from poor (observation method without information) to good (force transducers method and observation method with information). The measurement methods correlated moderately over all five tasks. Predictions of grip force across all five tasks were poor and even for single tasks the predictions were not much better. The tasks in this study were still simplified; in the field tasks are even more complex and the measurement characteristics might be expected to be less good. A hand force exposure assessment method should therefore be calibrated and tested for each type of hand activity before use.


[Deamination of adenine and adenosine in staphylococci].
Deaminations of adenine and adenosine by pattern strains of 24 staphylococcal species, were tested. During 3 hours of incubation of the suspensions of 8 staphylococci with adenine the liberation of ammonia occurred. The same staphylococci accumulated ammonia in the incubation medium with adenosine. The Staphylococcus intermedius PCM 2405 strain as opposite to the Staphylococcus aureus 536 strain in the media with adenine or adenosine accumulated hypoxanthine or inosine, respectively and ammonia. These results indicated that adenine deaminase (adenase) and adenosine deaminase activities were associated with the cells of the Staphylococcus intermedius PCM 2405 strain. Staphylococci were heterogeneous within three species groups with respect to adenine and adenosine deaminations. Adenine and adenosine determinations were absent in staphylococci belonging to the Staphylococcus simulans species group.


Attachable Pulse Sensors Integrated with Inorganic Optoelectronic Devices for Monitoring Heart Rates at Various Body Locations.
Monitoring cardiovascular signals such as heart rate and blood flow provides critically important healthcare information about patients under medical care. However, when the sensors are worn for extended times, the sensors sometimes require higher mechanical compatibility with soft deformable tissues. In this paper, we report an attachable and flexible pulse sensor (bending radius: 2.4 mm), integrated with micro-inorganic photodetectors (thickness: 4.1 μm, photocurrent: 8.99 μA under 1.5 mW/cm2) and a red light emitting diode (620 nm), to monitor vital signals for extended times. Operating in a reflection mode, it can be attached and measure heart pulse waveforms from various locations on the human body including the finger, fingertip, nail, and forearm. The small form factor also enables integration on a finger ring. Electrical and mechanical performance assessments demonstrated the practical feasibility of the concept.


Clinical indications for radical resection of odontogenic keratocyst: A systematic review.
The aim of this study was to identify clinico pathological indications for radical resection of odontogenic keratocysts (OKCs) in the literature and formulate clinical guidelines for the management of OKCs based on these findings. A systematic review of the literature was undertaken in September 2021 in PubMed/Medline, Scopus, Web of Science, Google Scholar, and Cochrane databases. The following MeSH Keywords terms were used in the search strategies: (odontogenic keratocyst) OR (keratocystic odontogenic tumor) OR (primordial cyst) AND (treatment) OR (Radical resection) OR (Resection of OKC) OR (Treatment methods). Eligibility criteria included publications of clinical studies on histologically confirmed OKCs which underwent radical resection. Studies with less than 5 OKCs, experimental studies, epidemiological studies, studies that included orthokeratinized odontogenic cyst, and review papers were excluded. Ten studies on OKCs reporting on segmental or marginal resections were identified and analyzed qualitatively. Of the total of 221 OKCs that underwent radical resection, 67 OKCs were primary, 30 were recurrent, and the remaining were unclear whether they were primary or recurrent. Segmental mandibulectomy was performed in 131 OKCs, marginal mandibulectomy in 87 OKCs, and 3 OKCs were treated by partial maxillectomy. The main indications for radical resection were multilocular appearance, large OKCs (> 5 cm), multiple recurrent OKCs with or without cortical perforation, and malignant transformation. In conclusion, radical resection has its place in the management of OKC. It is indicated when there is an aggressive lesion with bony perforation, involvement of the pterygoid musculature or skull base, and malignant transformation. The surgeon should aim to identify these features to manage OKC appropriately and to prevent multiple recurrences. Clinical guidelines for the management of OKCs are proposed.


One-year follow-up of basic body awareness therapy in patients with posttraumatic stress disorder. A small intervention study of effects on movement quality, PTSD symptoms, and movement experiences.
The present study with mixed methods design evaluated the long-term effects of Basic Body Awareness Therapy (BBAT) for patients with posttraumatic stress disorder (PTSD). Fifteen patients received 12 individual sessions of BBAT treatment as usual (TAU) when needed. The patients were assessed at baseline (T0), directly after treatment (T1) and at one-year follow-up (T2), using the Body Awareness Scale Movement Quality and Experience (BAS MQ-E), the Visual Analog Scale (VAS), and the Impact of Event Scale-Revised (IES-R). The results at T1 showed significant improvement in the quality of movement (p = 0.001), body experience (p = 0.007), and symptoms (p = 0.001). At T2, the improvements were sustained. Pain in stillness (p = 0.017) and during movement (p = 0.007) had decreased. The verbal ability to describe the body experiences in words was poor at T0, but became more detailed at T1 and even more so at T2. Our findings suggest that BBAT in addition to TAU can be a viable physiotherapeutic treatment for patients with PTSD. This knowledge may influence future treatment strategies for patients with PTSD and be of guidance to physiotherapists working with persons with trauma experiences in the community or psychiatry/mental healthcare areas.


The cancer stem cell marker CD133 interacts with plakoglobin and controls desmoglein-2 protein levels.
The pentaspan membrane glycoprotein CD133 (also known as prominin-1) has been widely used as a marker for both cancer and normal stem cells. However, the function of CD133 has not been elucidated. Here we describe a cancer stem cell line established from clear cell carcinoma of the ovary (CCC) and show that CD133 interacts with plakoglobin (also known as γ-catenin), a desmosomal linker protein. We further demonstrate that knockdown of CD133 by RNA interference (RNAi) results in the downregulation of desmoglein-2, a desmosomal cadherin, and abrogates cell-cell adhesion and tumorigenicity of CCC stem cells. We speculate that CD133 may be a promising target for cancer chemotherapy.


Hereditary angioedema: Screening of first-degree blood relatives and earlier diagnosis.
Background: Hereditary angioedema (HAE) with C1 inhibitor (C1INH) deficiency is an inherited disease characterized by sudden, recurrent episodes of edema that involve the skin, gastrointestinal tract, respiratory tract, and other organs. Objective: Because it takes a long time from the first symptoms to diagnosis, we aimed to identify HAE in untested first-degree blood relatives among some of our patients with HAE in our outpatient clinic at Hospital Universitário Clementino Fraga (HUCFF), Federal University of Rio de Janeiro. Methods: Untested first-degree relatives of patients with HAE C1INH, even those who were asymptomatic, were identified and invited to participate. Those who agreed to participate answered a specific questionnaire and had a blood sample collected for complement testing. Results: Fifty untested first-degree relatives of 30 index patients with HAE C1INH were identified, and both groups were analyzed. The mean ± standard deviation (SD) age of the index patients group was 37.08 ± 16.56 years (range, 13-73 years), with a high frequency in women (n = 24 [80.0%]). Most of them had severe (n = 23 [76.7%]) and moderate (n = 7 [23.3%]) attacks. None were asymptomatic. The mean ± SD time between the first symptoms and diagnosis was 20.2 ± 11.06 years (range, 0-48 years) in that group. In the first-degree relatives group, 30 new cases of HAE C1INH (60%) were identified. Conclusion: We found that there was a long time between early manifestations and a diagnosis of HAE. First-degree relatives of patients with HAE patients are at risk for having the disease. Sixty percent were newly diagnosed with HAE and with C1INH deficiency in our study. So, screening of family members, including individuals who were asymptomatic, is the key for earlier diagnosis and effective treatment.


Fatal injury surveillance report, Delaware, 1990. Head and spinal cord injuries.
The Delaware Disabilities Prevention Program is funded through a five-year Centers for Disease Control and Prevention (CDC) grant to prevent primary and secondary disabilities associated with mental retardation and low socioeconomic status; head and spinal cord injuries; and sickle cell disease. This report focuses on fatal head and spinal cord injuries. Death certificates and autopsy reports from 1990 were the data sources used for this study. In 1990, 122 fatal head injuries and 20 fatal spinal cord injuries occurred among Delaware residents. Eight of these individuals experienced both head and spinal cord injuries. Motor vehicle crashes caused the majority of both head and spinal cord deaths. Suicides, homicides, and falls were the other major causes of fatal head injuries. Deaths are only the tip of the injury iceberg. Head and spinal cord injuries can cause lifelong disabilities affecting family, friends, and the entire community.


Are we accurately predicting bladder capacity in infants?
Estimating bladder capacity is an important component in the evaluation of many urological disorders. For estimates to be of clinical value, precise reference ranges are needed. While accepted reference ranges have been established in adults and older children, none have been validated in infants. We endeavour to determine the normal bladder capacity of children less than 1 year of age. We retrospectively reviewed the charts of children aged 0 to 12 months with cutaneous stigmata of spinal dysraphism who were referred to the urology clinic to rule out tethered cord between October 2004 and July 2011. Patients with normal urologic assessment, who did not have surgery during the time they were followed, were included in the study cohort. Urodynamic studies were performed using the Laborie Medical Technologies UDS-600. Bladder filling occurred via a catheter at a rate of 10% of the expected total bladder capacity/minute. Bladder capacity was defined as the volume of filling when the child voided around the catheter. We collected data, including age at urodynamics, bladder capacity, detrusor pressure at capacity, bladder compliance and length of follow-up. In total, 46% (84/183) of patients had a normal urologic assessment and met the inclusion criteria. The median age was 9.0 months (interquartile range [IQR] 6.8-11.0). The average bladder capacity was 48.9 mL (standard deviation [SD] 32.8) and the mean detrusor pressure at capacity was 8.5 cmH2O (SD 10.0). Mean compliance was 14.1 mL/cmH2O (SD 13.6). The average length of follow-up was 40.7 months (SD 26.2) and during this interval no patients were found to have urologic or neurologic abnormalities and none underwent tethered cord release. Bladder capacity in infants with a median age of 9.0 months was found to be 48.9 mL. This is less than half of the volume predicted by a commonly employed formula. A novel method of estimating bladder capacity in infants is required.