Synthesis and characterization of beta-haloalkenyl-lambda3-bromanes: stereoselective Markovnikov addition of difluoro(aryl)-lambda3-bromane to terminal acetylenes.
Reported here for the first time are the synthesis, isolation, and characterization of hypervalent beta-haloalkenyl-lambda3-bromanes. Exposure of terminal alkynes to p-trifluoromethylphenyl(difluoro)-lambda3-bromane activated by BF3-i-Pr2O resulted in fluoro-lambda3-bromanation of the triple bonds in a Markovnikov fashion, yielding (E)-beta-fluoroalkenyl-lambda3-bromanes stereoselectively in good yields. 5-Chloro-1-pentynes undergo domino lambda3-bromanation-chlorine shift-fluorination or lambda3-bromanation-chlorine shift-alkyl shift-fluorination reaction, depending on the substituents and afford (E)-beta-chloroalkenyl-lambda3-bromanes stereoselectively in high yields. The beta-chloroalkenyl-lambda3-bromanes contain three kinds of halogen atoms, F, Cl, and Br, in the molecule.


Hsa_circ_0002496 promotes the growth, angiogenesis, and stemness of breast cancer cells via miR-433-3p/YWHAZ cascade.
Breast cancer (BC) has been studied more and more in modern medicine. Circ_0002496 has established a critical role in BC. MiR-433-3p can exert important activity in cancer. YWHAZ can participate in BC development, but the targeting relationship among the three variables and its influence on the related process of BC are not clear. RT-qPCR was used to analyze circ_0002496, miR-433-3p, and YWHAZ expression. Immunoblotting was used to analyze YWHAZ, Bax, Bcl-2, and PI3K/AKT-related proteins. RNase R assay was used to verify the ring structure of circ_0002496. Cell phenotypes were tested by Cell Counting Kit 8, EdU, sphere formation, tube formation, and flow cytometry assays. Circ_0002496 was enhanced and MiR-433-3p was downregulated in BC, while the expression of YWHAZ was higher in BC. Circ_0002496 targeted miR-433-3p and miR-433-3p targeted YWHAZ in BC cells. Depletion of circ_0002496 influenced the BC process, but miR-433-3p inhibitor reversed the impact of si-circ_0002496 on the BC process. Re-expression of YWHAZ weakened the influence of miR-433-3p on the BC process. Depletion of circ_0002496 could astrict tumor growth in vivo. Moreover, the circ_0002496/miR-433-3p/YWHAZ axis mediated the activation of the PI3K/AKT signaling pathway. Circ_0002496 participated in the malignant procession of BC by miR-433-3p/YWHAZ regulation cascade.


The severity of SARS-CoV-2 infection is dictated by host factors? Epigenetic perspectives.
The emergence of COVID-19, caused by SARS-CoV-2 poses a significant threat to humans as it is highly contagious with increasing mortality. There exists a high degree of heterogeneity in the mortality rates of COVID-19 across the globe. There are multiple speculations on the varying degree of mortality. Still, all the clinical reports have indicated that preexisting chronic diseases like hypertension, diabetes, chronic obstructive pulmonary disease (COPD), kidney disorders, and cardiovascular diseases are associated with the increased risk for high mortality in SARS-CoV-2 infected patients. It is worth noting that host factors, mainly epigenetic factors could play a significant role in deciding the outcome of COVID-19 diseases. Over the recent years, it is evident that chronic diseases are developed due to altered epigenome that includes a selective loss/gain of DNA and histone methylation on the chromatin of the cells. Since, there is a high positive correlation between chronic diseases and elevated mortality due to SARS-CoV-2, in this review; we discuss the overall picture of the aberrant epigenome map in varying chronic ailments and its implications in COVID-19 disease severity and high mortality.


In-depth analysis of eight susceptibility loci of primary angle closure glaucoma in Han Chinese.
Primary angle closure glaucoma (PACG) is a multifactorial disease with genetic predisposition. Primary angle closure (PAC) is the early stage of PACG and they share the same anatomical characteristics. We aimed to examine whether the PACG associated-genetic loci identified previously by genome-wide association study (GWAS) were also related to primary angle closure disease (PACD) in Han Chinese. This cross-sectional case-control study consisted of 232 PAC, 264 PACG and 306 controls. Eight single-nucleotide polymorphisms (SNPs) of PACG susceptibility loci within PLEKHA7, COL11A1, PCMTD1-ST18, EPDR1, CHAT, GLIS3, FERMT2, DPM2-FAM102A were genotyped using participants' blood samples. We excluded 3 SNPs for PAC analysis because the data has been reported using the same sample set. Anatomical parameters such as axial length (AL), anterior chamber depth (ACD) and lens thickness (LT) were included as phenotypes for the association analysis. Allelic and genotypic model tests were performed. Three among the eight SNPs were found to be significantly associated with PACG, e.g. PLEKHA7 rs11024102 in additive, dominant and recessive model; and both CHAT rs1258267 and DPM2-FAM102A rs3739821 in dominant model. CHAT rs1258267 showed marginal association with PAC in dominant model. Anatomical parameters were not found to link to the eight SNPs after Bonferroni multiple test correction. Our data suggest that PLEKHA7 and DPM2-FAM102A might exert effect in the late stage of the PACD, while CHAT may play a broad role in both early and late stages of the PACD.


Malnutrition is associated with depression in rural elderly population.
Aging induces physiological changes and affects all of organs. Nutritional status and mental health deteriorate with aging. As malnutrition and depression are main problem in elderly this study was performed to assess the association between malnutrition and depression among rural elderly. Three hundred and seventy rural elderly aged over 60 years were examined in a cross-sectional study by systematic sampling method and using mini nutritional assessment (MNA), which is a standard questionnaire for evaluating nutrition status. Depression was evaluated by a validated questionnaire in the elderly. Correlation between Socio-demographic characteristic, diseases, and nutrition status was obtained by t-test, Chi-square test and logistic regression in elderly population. Mean ± SD age was 70.6 ± 7.3 years. Frequency of malnutrition was similar in both genders. According to MNA, 3.8% of subjects suffered from malnutrition, 32.7% were at risk of malnutrition and 63.5% were well-nourished. Nutrition status correlated with body mass index (P = 0.028) and depression (P = 0.001). The risk of severe depression in patients with malnutrition was 15.5 times higher than non-depressed persons (odd ratio: 15.5; 95% CI: 2.9-82.5). Depression could act as a powerful risk for malnutrition in elderly population that it should be controlled by physicians.


Complement regulation in human atherosclerotic coronary lesions. Immunohistochemical evidence that C4b-binding protein negatively regulates the classical complement pathway, and that C5b-9 is formed via the alternative complement pathway.
The complement system is activated in human atherosclerotic lesions and may hence aggravate local inflammation. We studied the presence and localization of C4b-binding protein (C4bp), the major inhibitor of the classical complement pathway, in human atherosclerotic lesions in relation to complement activation products and protein S, which circulates in complex with C4bp. Immunohistochemistry of human coronary arteries showed C4bp to be virtually absent in normal arteries but present in early and advanced atherosclerotic lesions. In the lesions, C4bp is associated with proteoglycans, and affinity chromatography showed that C4bp interacts with human arterial proteoglycans. Areas containing C4bp also contained IgM and C4 suggesting that C4bp is involved in the regulation of the classical complement pathway. However, C5b-9 was virtually absent in these areas but, instead, colocalized with properdin deeper in the intima, suggesting that C5b-9 is formed by the alternative complement pathway. A fraction of C4bp was associated with protein S and apoptotic cells. The results indicate that C4bp regulates the classical complement pathway in human atherosclerotic lesions. Thus, unlike the alternative pathway, the classical complement pathway does not generate C5b-9, but is likely to be involved in the clean-up of apoptotic cells and cell debris in the arterial intima.


Women A.A. members and nonalcoholics; scores on the Holmes and MacAndrew Scales of the MMPI.
Three groups of women-members of Alcoholics Anonymous, psychiatric inpatients and normal subjects--showed no significant differences in scores on the Holmes and MacAndrew Scales of the MMPI.


Aflatoxin and ochratoxin A content of spices in Hungary.
In October and November 2004, 91 spice samples (70 ground red pepper, six black pepper, five white pepper, five spice mix and five chilli samples), the majority of which originated from commercial outlets, were analysed for aflatoxins B1, B2, G1 and G2 (AFB1, AFB2, AFG1, AFG2) and ochratoxin A (OTA) content by high-performance liquid chromatography (HPLC) after immunoaffinity column clean-up. Eighteen of the 70 ground red pepper samples contained AFB1, seven of them in a concentration exceeding the 'maximum level' of 5 microg kg(-1) (range 6.1-15.7 microg kg(-1)). Of the other spices assayed, the AFB1 contamination of one chilli sample exceeded 5 microg kg(-1) (8.1 microg kg(-1)). Thirty-two of the 70 ground red pepper samples contained OTA, eight of them in a concentration exceeding the 10 microg kg(-1) 'maximum level' (range 10.6-66.2 microg kg(-1)). One chilli sample was contaminated with OTA at 2.1 microg kg(-1). The AFB1 and OTA contamination of ground red pepper exceeding the 'maximum level' (5 and 10 microg kg(-1), respectively) was obviously the consequence of mixing imported ground red pepper batches heavily contaminated with AFB1 and OTA with red pepper produced in Hungary. This case calls attention to the importance of consistently screening imported batches of ground red pepper for aflatoxin and ochratoxin A content and strictly prohibiting the use of batches containing mycotoxin concentrations exceeding the maximum permitted level.


Factors influencing compliance to the infection control precautions among nurses and physicians in Jordan: A cross-sectional study.
Adherence to infection control precautions (ICP) is important to reduce the transmission of healthcare-associated infections (HAIs). To determine nurses and physician's knowledge, attitude and compliance to ICPs and factors associated with reported compliance. A cross-sectional survey of nurses and physicians recruited from three hospitals at three different healthcare sectors in Jordan. Three instruments were used to assess knowledge, attitudes and compliance to ICPs. A total of 211 professionals completed the survey: 155 nurses and 56 physicians. Both groups had low knowledge scores for ICP but a high positive attitude. Although both groups had high reported compliance scores, nurses scores were higher (P = 0.04). Participants from the private hospital had higher knowledge and compliance scores. Length of experience, knowledge and attitude were significant predictors of reported compliance to ICPs. Despite poor knowledge, Jordanian healthcare professionals reported high scores for positive attitudes and compliance with IPCs. Clinical training programmes are required to enhance knowledge and understanding of IPCs.


Chocolate cysts of the orbit.
Acute spontaneous development of proptosis and periorbital ecchymosis may be the presenting sign of an orbital lymphangioma. This benign hamartoma should not be confused with other orbital malignancies.


Bmp-2 downstream targets in mesenchymal development identified by subtractive cloning from recombinant mesenchymal progenitors (C3H10T1/2).
ABmp-dependent in vitro model was used to identify cDNAs during the manifestation of mesenchymal lineages. This model involves the recombinant expression of Bmps (Bmp-2, Bmp-4-7) in murine mesenchymal C3H10T1/2 progenitors, which leads to the differentiation into three lineages: the osteogenic, the chondrogenic and the adipogenic lineage, albeit in varying efficiencies. By subtractive cloning, 21 Bmp-2-regulated cDNAs from C3H10T1/2 mesenchymal progenitors were identified; 20 were related to known sequences and 1 was not. During mouse embryonic development, many of these cDNAs are expressed in chondrogenic, osteogenic, and in adipogenic tissues. Novel findings include a G0/G1 switch gene (G0S2), which was demonstrated to be predominantly expressed in adipose tissue during late murine embryonic development. Furthermore, the membrane-standing glycoprotein autotaxin (ATX) is expressed, at precartilage condensations, joint regions, and during tooth development. An as yet undescribed cDNA, 29A, which encodes a putative secreted factor, is expressed in developing osteo-/chondrogenic tissues of vertebrae, ribs, tooth, and the limb bud. C3H10T1/2-progenitors, therefore, may serve as a legitimate model for the investigation of the Bmp-mediated events during mesenchymal differentiation.


Using MAIAC AOD to verify the PM2.5 spatial patterns of a land use regression model.
Accurate spatial information of PM2.5 is critical for air pollution control and epidemiological studies. Land use regression (LUR) models have been widely used for predicting spatial distribution of ground PM2.5. However, the predicted PM2.5 spatial patterns of a LUR model has not been adequately examined due to limited ground observations. The increasing aerosol optical depth (AOD) products might be an approximation of spatially continuous observation across large areas. This study established the relationship between seasonal 1 km × 1 km MAIAC AOD and observed ground PM2.5 in Beijing, and then seasonal PM2.5 maps were predicted based on AOD. Seasonal LUR models were also developed, and both the AOD and LUR models were validated by hold-out monitoring sites. Finally, the spatial patterns of LUR models were comprehensively verified by the above AOD PM2.5 maps. The results showed that AOD alone could be used directly to predict the spatial distribution of ground PM2.5 concentration at seasonal level (R2 ≥ 0.53 in model fitting and testing), which was comparable with the capability of LUR models (R2 ≥ 0.81 in model fitting and testing). PM2.5 maps derived from the two methods showed similar spatial trend and coordinated variations near traffic roads. Large discrepancies could be observed at urban-rural transition areas where land use characters varied quickly. Variable and buffer size selection was critical for LUR model as they dominated the spatial patterns of predicted PM2.5. Incorporating AOD into LUR model could improve model performance in spring season and provide more reliable results during testing.


Control of minicell producing cell division by cAMP-receptor protein complex in Escherichia coli.
It has been established that the strain CA8000 of Escherichia coli K12 produces minicells. This phenotype of CA8000 has been shown to be suppressed by additional mutations in cya or crp genes. Minicell production by cya+ crp+ min bacteria is probably a consequence of error, introduced by horizontal growth, in the selection of site on the envelope for initiation of hemispherical growth.


Radiation therapy in anal and rectal cancer.
Historically, squamous cell carcinoma of the anal canal was treated with abdominoperineal resection. Nigro discovered that radiation therapy combined with 5-fluorouracil and mitomycin resulted in high rates of local control and colostomy-free and overall survival without surgical intervention. Recent advances include the integration of PET into staging, radiation treatment planning, disease monitoring, and the use of intensity-modulated radiation therapy. For rectal cancer, clinical trials have established the role for neoadjuvant therapy for T3-4 and/or node-positive tumor presentations. Chemotherapy and targeted agents are under study in both anal and rectal cancers to improve on the standard combinations of chemotherapy and radiation.


Upper lip reconstruction: use of the free superficial temporal artery hair-bearing flap.
The use of the superficial temporal artery hair-bearing flap applied to the repair of burn injuries to the upper lip of two male patients is described. It is a relatively simple method of providing tissue to the injured lip with advantages over traditional methods in that it is single-staged and provides the possibility for hair growth in the form of a camouflaging moustache. Donor site morbidity is minimal. When combined with additional reconstructive procedures in the multiply-injured male face, it provides a reasonable expectation for the patient of an acceptable appearance.


Anti-PD-1 immunotherapy combined with stereotactic body radiation therapy and GM-CSF for the treatment of advanced malignant PEComa: A case report.
Perivascular epithelioid cell neoplasm (PEComa) is a rare mesenchymal tumour. Due to its low incidence, a standard treatment regimen for PEComa has not yet been established. Radiotherapy has a synergistic effect with PD-1 inhibitors and GM-CSF. We treated advanced malignant PEComa with a triple regimen of PD-1 inhibitor, SBRT and GM-CSF to provide better therapeutic effect. A 63-year-old woman was diagnosed with malignant PEComa after presenting with postmenopausal vaginal bleeding. Despite two surgeries, the neoplasm eventually metastasized throughout the body. We formulated triple therapy with SBRT, a PD-1 inhibitor, and GM-CSF for the patient. The patient's local symptoms were controlled at the radiotherapy site, and the lesions at the unirradiated sites were also relieved. For the first time, a triple regimen of PD-1 inhibitor, SBRT and GM-CSF was used in the treatment of malignant PEComa and achieved good efficacy. Considering the lack of prospective clinical studies in PEComa, we believe that this triple therapy is a good-quality regimen for advanced malignant PEComa.


Exosome-transmitted FOSL1 from cancer-associated fibroblasts drives colorectal cancer stemness and chemo-resistance through transcriptionally activating ITGB4.
Cancer-associated fibroblasts (CAFs) have been proved to facilitate colorectal cancer (CRC) development, either with boosting chemo-resistance by communicating with CRC cells in the tumor microenvironment. However, the underlying molecular mechanisms remain largely unclear. Relative expressions of FOSL1 and ITGB4, either with their correlations in CRC tissues, were assessed using qRT-PCR analysis. Also, Kaplan-Meier survival analysis was employed for evaluating the prognosis. Identification of CAFs was determined by the detection of specific makers (α-SMA, FAP, and FSP1) using western blot and immunofluorescence staining. Cell proliferation, self-renewal capacity, and cell apoptosis were estimated by CCK-8, sphere-formation, and flow cytometry assays. Transcriptional regulation of FOSL1 on integrin β4 (ITGB4) was confirmed using ChIP and dual-luciferase reporter assays. Increased FOSL1 and ITGB4 in CRC tissues were both positively correlated with the poor prognosis of CRC patients. Interestingly, FOSL1 was enriched in the CAFs isolated from CRC stroma, instead of ITGB4. CRC cells under a co-culture system with CAFs-conditioned medium (CAFs-CM) exhibited increased FOSL1, promotive cell proliferation, and reduced apoptosis, while these effects could be blocked by exosome inhibitor (GW4869). Moreover, CAFs-derived exosomal FOSL1 was validated to enhance proliferative ability and oxaliplatin resistance of CRC cells. Our results uncovered that CAFs-derived exosomes could transfer FOSL1 to CRC cells, thereby promoting CRC cell proliferation, stemness, and oxaliplatin resistance by transcriptionally activating ITGB4.


Management and outcomes of pseudoaneurysms presenting with late hemorrhage following pancreatic surgery: A six-year experience from a tertiary care center.
Late hemorrhage following pancreatic surgery is associated with significant morbidity and mortality. Pseudoaneurysm (PSA) is an important source of late hemorrhage, which is effectively and safely managed by embolization. We aim to retrospectively review the outcomes of embolization for pseudoaneurysms causing late post-pancreatectomy hemorrhage over a period of six-years at our tertiary care center. Between 2014 and 2020, 616 pancreatic surgeries were performed and 25 patients had late hemorrhage (occurring > 24 hours post-operatively). The clinical parameters related to late hemorrhage, associated complications, embolization details, treatment success and their short-and long-term outcomes were analyzed. Sixteen of 25 patients had PSA on digital subtraction angiography. Embolization was performed in these patients with technical and clinical success rates of 94.1% and 100%, respectively. Compared to patients without PSA, patients with PSA had significant hemoglobin drop (2.5 g/dL vs. 1.5 g/dL, p = 0.01), higher incidence of sentinel bleed (50% vs. 11.1%, p = 0.05) and lower requirement for surgery for bleeding (0% vs. 44.4%, p = 0.02). Clincally relevant postoperative pancreatic fistula and bile leak were seen in 72% and 52% of patients, respectively. Eight of these embolized patients died due to sepsis. The long-term outcome was good, once the patients were discharged. Late hemorrhage after pancreatic surgery was associated with high mortality due to complications such as pancreatic fistula and bile leak. Sentinel bleeding was an important clinical indicator of PSA. Angiographic embolization is safe and effective without any adverse short or long-term outcomes.


Frequency and predictors of missed visits to primary care and eye care providers for annually recommended diabetes preventive care services over a two-year period among U.S. adults with diabetes.
This paper examines the patterns of visits to primary care and eye care providers for annually recommended diabetes preventive care services over a two-year period in a sample of U.S. adults aged 18years and older with diabetes drawn from the 2008-2013 Medical Expenditure Panel Survey-Household Component (n=3982). The four-category outcome variable was defined based on the four possible combinations of whether an individual missed an annual visit to a primary care provider for preventive care services in at least one year over the two-year period and whether the individual missed an annual visit to an eye care provider in at least one year over this period. Descriptive statistics and a multinomial logistic regression model were estimated. 51.9% of the sample missed an annual visit to a primary care or eye care provider for preventive care services over a two-year period. Although 48.8% of the sample missed at least one annual visit to an eye care provider, 85.6% of these individuals did visit a primary care provider for preventive care services during the year they did not visit an eye care provider. This suggests that primary care-based screening for diabetic retinopathy could reach most individuals who do not receive regular eye care. Regression results particularly relevant for potential interventions were that missing annual visits was significantly more likely for individuals without health insurance or a usual source of healthcare and for those who were not receiving diabetes treatments and did not have or were not aware of having diabetes-related complications.


[Histological study of conjunctiva-associated lymphoid tissue in mice].
To investigate conjunctiva-associated lymphoid tissue (CALT) in mouse conjunctiva. We examined normal mice, ranging in age from 4 to 6 weeks, to investigate the presence of follicular tissue histologically. Next, we treated mice by topical instillation of ovalbumin and cholera toxin B, and then examined conjunctival follicles by immunohistological methods. Follicular tissue was present at the nictitating membrane. Both size and amount of follicular tissue was increased by the topical ovalbumin treatment. Immunohistological examination revealed CD4, CD8, and S-100 protein positive cells in follicular tissue. The epithelial layer, corresponding to follicular tissue, had intraepithelial pockets and CD4 positive cells in the pockets. It was concluded that the follicular tissue at the nictitating membrane is CALT in mice.


An organ-on-chip model of pulmonary arterial hypertension identifies a BMPR2-SOX17-prostacyclin signalling axis.
Pulmonary arterial hypertension (PAH) is an unmet clinical need. The lack of models of human disease is a key obstacle to drug development. We present a biomimetic model of pulmonary arterial endothelial-smooth muscle cell interactions in PAH, combining natural and induced bone morphogenetic protein receptor 2 (BMPR2) dysfunction with hypoxia to induce smooth muscle activation and proliferation, which is responsive to drug treatment. BMPR2- and oxygenation-specific changes in endothelial and smooth muscle gene expression, consistent with observations made in genomic and biochemical studies of PAH, enable insights into underlying disease pathways and mechanisms of drug response. The model captures key changes in the pulmonary endothelial phenotype that are essential for the induction of SMC remodelling, including a BMPR2-SOX17-prostacyclin signalling axis and offers an easily accessible approach for researchers to study pulmonary vascular remodelling and advance drug development in PAH.


Early decreased plasma levels of factor B and C5a are important biomarkers in children with Kawasaki disease.
The mechanisms underpinning Kawasaki disease (KD) are incompletely understood. There is an unmet need for specific biomarkers for the early diagnosis of KD. Eighty-five KD patients suffering from acute-phase and subacute-phase KD, 40 healthy children, and 40 febrile children comprised the study cohort. An enzyme-linked immunosorbent assay was used to measure plasma levels of C1q, C1q-circulating immune complex (C1q-CIC), mannan-binding lectin-associated serine protease (MASP)-1, factor B, C4d, C3d, C5a, C5b-9 and CD59. Plasma concentrations of factor B and C5a in the acute phase were lower than those in healthy and febrile control groups (all P < 0.05). Compared with acute-phase KD patients, plasma concentrations of C1q, factor B, and C3d in KD patients were increased significantly (P < 0.05), but those of C4d, MASP-1 and CD59 decreased significantly (P < 0.05), in patients with sub-acute KD. These data suggest that more than one pathway in the complement system is activated in KD. Importantly, decreased plasma concentrations of factor B and C5a in the acute phase (6-10 d) could be employed as biomarkers for the early diagnosis of KD.


Case study: design may influence use of seclusion and restraint.
The psychiatric emergency room is a dynamic and sometimes volatile environment. Its design may be an important variable in patient care, but most design decisions are based on models of thought and treatment with a minimal evidence base. The concept of open design, increasing access of patients to nursing staff, for inpatient psychiatric units has recently gained widespread acceptance, despite a dearth of empirical data. We examined rates of seclusion and restraint before and after a design change that reduced the openness of the unit in a dedicated emergency psychiatric service in a general university hospital. Quality assurance data regarding the census, occurrence of assaults, and the use of seclusion and restraint were queried. Two independent analyses utilizing a test of proportional data were performed to replicate the findings. After placement of a door to restrict patients' access to the waiting area of the unit, the rate of the use of seclusion and restraint went from 0.03 (44/777) to 0.0185 (27/1,514; z = 2.02, p < .04). Replication over a separate time period saw reduction from 0.029 (67/2,277) to 0.018 (44/2,431), z = 2.44, p < .02). A design change that reduced the openness of the unit resulted in the reduction of seclusion and restraint.


Rett syndrome: Swedish approach to analysis of prevalence and cause.
The prevalence of the Rett syndrome was found to be approximately 1:15,000 in south-western Sweden. About 40 cases have now been traced in this country, the majority during the last 2 yrs. Experiences of over 20 yrs in efforts to obtain information on the etiology and pathogenesis are summarized. The neurobiological approach used in Gothenburg today to try to reveal the origin is described. A plea is made for developmental screening of deteriorating hand skill as a tool for early identification of potential cases of the Rett syndrome.


Twenty-four-hour urinary sodium and potassium excretion and associated factors in Japanese secondary school students.
Data on the sodium and potassium intake using dietary records among schoolchildren are sorely lacking in the Japanese literature. Some evidence indicates that sodium and potassium intake has been correctly measured, but information concerning these associated factors is scarce. The 24-h urine samples and first morning voiding (overnight) samples were collected twice from 68 secondary schoolchildren in Suo-Oshima Town, Japan. Sodium, potassium and creatinine concentrations were analyzed. Body height and weight were measured, and menstruation and physical activity were assessed via questionnaires. We analyzed the 24-h samples with a >20-h collecting period and no missed voiding. The 24-h sodium excretion was 163.2±36.8 and 149.8±45.1 mmol per 24 h for the boys and girls, respectively. Considering daily habits and loss from sweat, intake was assumed to be 10.6±1.2 and 10.0±2.4 g per day for the boys and girls, respectively. The 24-h potassium excretion was 43.4±10.8 and 45.8±14.4 mmol per 24 h for the boys and girls, respectively. Estimated usual potassium intake was 2195±401 and 2330±630 mg per day for the boys and girls, respectively. Sodium excretion was associated with sodium and potassium concentrations in overnight urine samples and physical activity. Potassium excretion was associated with height and physical activity. We described daily sodium and potassium excretion in Japanese secondary schoolchildren. Excretion was associated more with physical activity than with bodyweight. Therefore, the estimation methods used in adults are not applicable for use in adolescents.


[Value of combining biologics with methotrexate for treatment of psoriatic arthritis-questions remain].
Concomitant methotrexate (MTX) improves the therapeutic effect of biologic therapies in rheumatoid arthritis treatment. However, the influence of MTX on biologic therapy in psoriasis arthritis (PsA) has not yet been fully clarified, as data from randomized clinical studies are lacking. So far, it is only known, that PsA patients with inadequate response to MTX or non-steroidal anti-inflammatory drugs alone respond equally well to a subsequent biologic therapy. The aim of this study is to investigate whether MTX-naive patients achieve greater disease improvement with the combination of MTX and a biologic than with biologic monotherapy alone, and whether patients on MTX in whom a biologic therapy is additionally started would worsen if MTX is discontinued. The current data situation and its limitations are presented. Furthermore, an investigator-initiated multicenter randomized clinical study in patients with active PsA is introduced (MUST study), which investigates the influence of placebo-controlled MTX combination therapy with the interleukin 12/23 inhibitor ustekinumab (UST) in order to close the existing evidence gap. The primary objective of the study is to demonstrate the non-inferiority of UST monotherapy compared to MTX/UST combination therapy as measured by mean DAS28 values at week 24. Of 196 planned patients, 77 have been included so far. Recruitment is still open. The MUST study offers the ideal opportunity to investigate the influence of concomitant MTX in a controlled study design and to assess whether the addition of MTX to UST therapy or its continuation is beneficial for PsA patients.


Long-term risk of recurrent vascular events and mortality in young stroke patients: Insights from a multicenter study.
Although the incidence of stroke in the young is rising, data on long-term outcomes in these patients are scarce. We thus aimed to investigate the long-term risk of recurrent vascular events and mortality in a multicenter study. We followed 396 consecutive patients aged 18-55 years with ischemic stroke (IS) or transient ischemic attack (TIA) enrolled in three European centers during the period 2007-2010. A detailed outpatient clinical follow-up assessment was performed between 2018 and 2020. When an in-person follow-up visit was not possible, outcome events were assessed using electronic records and registry data. During a median follow-up of 11.8 (IQR 10.4-12.7) years, 89 (22.5%) patients experienced any recurrent vascular event, 62 (15.7%) had any cerebrovascular event, 34 (8.6%) had other vascular events, and 27 (6.8%) patients died. Cumulative 10-year incidence rate per 1000 person-years was 21.6 (95% CI 17.1-26.9) for any recurrent vascular event and 14.9 (95% CI 11.3-19.3) for any cerebrovascular event. The prevalence of cardiovascular risk factors increased over time, and 22 (13.5%) patients lacked any secondary preventive medication at the in-person follow-up. After adjustment for demographics and comorbidities, atrial fibrillation at baseline was found to be significantly associated with recurrent vascular events. This multicenter study shows a considerable risk of recurrent vascular events in young IS and TIA patients. Further studies should investigate whether detailed individual risk assessment, modern secondary preventive strategies, and better patient adherence may reduce recurrence risk.


Neuro-Behçet's syndrome: differential diagnosis and management.
Behçet's syndrome (BS) is a multisystem disease of unknown etiology, characterized by chronic relapsing cardinal symptoms of orogenital ulcers, uveitis, and different skin lesions. Its major pathologic feature is vasculitis. Neuro-Behçet's syndrome (NBS) is defined as a constellation of neurologic manifestations with characteristic neuropathologic findings, usually confirmed by ancillary investigations, in patients who meet the diagnostic criteria for BS. Neurologic manifestations of the syndrome are more common in male patients and have been reported to occur in anywhere from 5% to 50% of BS patients, depending on their geographical region. NBS primarily affects the central nervous system and includes parenchymal and nonparenchymal involvement. Peripheral neuropathy and myopathy are rare. Immunosuppression is widely used for treatment.


Rhombencephalitis and Myeloradiculitis Caused by a European Subtype of Tick-Borne Encephalitis Virus.
We report a case of a previously healthy man returning to the United Kingdom from Lithuania who developed rhombencephalitis and myeloradiculitis due to tick-borne encephalitis. These findings add to sparse data on tick-borne encephalitis virus phylogeny and associated neurologic syndromes and underscore the importance of vaccinating people traveling to endemic regions.


Complete sequence of a double-stranded RNA from the phytopathogenic fungus Erysiphe cichoracearum that might represent a novel endornavirus.
A double-stranded RNA (dsRNA) HBJZ1506 recovered from the phytopathogenic fungus Erysiphe cichoracearum infecting Calendula officinalis in Jingzhou, Hubei Province, China, was sequenced. HBJZ1506 comprises 11,908 nucleotides (nt) and contains a 11,859-nt-long open reading frame (ORF) coding for a polypeptide that is 61 % identical to that of a putative endornavirus named grapevine endophyte endornavirus (GeEV). The putative polyprotein has an RNA-dependent RNA polymerase (RdRp) domain and an RNA helicase domain, which show homology to and have an arrangement that is similar to that of their counterparts in approved or putative endornaviruses. In a phylogenetic tree constructed using amino acid sequences of the RdRp region of HBJZ1506 and selected endornaviruses, HBJZ1506 clustered with endornaviruses and formed a well-supported monophyletic branch with GeEV. These results suggest that HBJZ1506 might represent a novel endornavirus, for which the name Erysiphe cichoracearum endornavirus (EcEV) is proposed.


The effect of changing to Bictegravir on lipids using real world data: A brief report.
Cardiovascular disease is of increasing concern in patients living with HIV. The significant advancement in antiretroviral treatment has ensured that patients are now succumbing to traditional diseases of ageing. First generation antiretroviral therapy caused multiple side effects including significant dyslipidaemia. Despite the advancement and improving safety profile of treatment concerns remain about antiretroviral induced dyslipidaemia. We sought to investigate the real-world effect on lipids in patients switching to a Bictegravir based regime. We conducted a retrospective analysis in patients switching therapy to Biktarvy at the Royal Liverpool University Hospital. Data was collected from the HIV database that is established for clinical use, as an electronic patient record, and audit purposes. Lipid data was cross checked with the Trust electronic reporting system. Participants were included if they were HIV-positive, >18 years and had switched to Biktarvy Patients were also required to have a lipid profile available 52 weeks prior to switching and 100 weeks post switching. Summary statistic were calculated and multiple regressions models were constructed to assess the independent predictors of lipid change. We also performed one way analysis of covariance (ANCOVA) to assess the impact of switching therapy on each quartile of the baseline lipid panel. There were 135 patients included in the analysis with a mean age of 47. The majority of the population were male (80%). At a mean follow up of 42 weeks post switch there was no significant difference in total cholesterol (p = 0.64), triglyceride (p = 0.64) or high density lipoprotein (HDL) cholesterol (p = 0.08). In the regression analysis the highest quartile of baseline total cholesterol and triglyceride were independently associated with improvement in lipid markers. Switching from protease inhibitor therapy was also significantly associated with improvement in triglyceride. In addition, the ANCVOA demonstrated that the highest quartiles of total cholesterol, triglyceride and the lowest quartile of HDL were associated with significant improvement in lipid markers after switching to Bictegravir. We demonstrated that patients with the most adverse lipid profiles at baseline had significant improvements in lipid profiles. In addition, patient switching away from protease inhibitor therapy also had significant improvements in triglyceride.


The effect of 2,3-diphosphoglycerate on the tetramer-dimer equilibrium of carbon monoxide hemoglobin in dilute solution. Correlation between sedimentation and kinetic behavior.
The effect of 2,3-diphospho-D-glycerate on the sedimentation coefficient of carbon monoxide hemoglobin was correlated with the fraction of rapidly reacting hemoglobin observed subsequent to flash photolysis at 23 degrees C at pH 7.30 in buffers of 0.1 M ionic strength. Concentrations of the organic phosphate up to about 5 mM resulted in an increase in S20,w, consistent with an increase in the fraction of tetrameric hemoglobin. A decrease in rapidly reacting hemoglobin parallelled the increase in the sedimentation coefficient. Between 5 and 20 mM 2,3-diphosphoglycerate, S20,w decreased, suggesting that dissociation to dimers was enhanced. An increase in rapidly reacting hemoglobin was also observed in this concentration range. Similar sedimentation results were obtained with oxyhemoglobin at pH 7.00 and carbon monoxide hemoglobin at pH 7.06. Assuming single binding sites on each species, the dissociation constants for 2,3-diphosphoglycerate binding to tetrameric and dimeric HbCO are 0.2-0.3 mM and 2-5 mM at pH 7.30. This biphasic effect of this physiologically important organic phosphate on the state of aggregation of R state hemoglobin has not been previously reported, but it is similar to that previously noted with inositol hexaphosphate, which enhanced tetramer formation at low concentrations, while at higher concentrations it promoted hemoglobin dissociation to dimers (White, S. L. (1976) J. Biol. Chem. 251, 4763-4769; Gray, R. D. (1980) J. Biol. Chem. 255, 1812-1818).


Activation of complement in human serum by some synthetic polymers used for intraocular lenses.
Determination of the potential to activate complement can be used as one criterion in testing the biocompatibility of various synthetic polymers that are utilized in the medical field. Intraocular lenses (IOLs) made of poly(methyl methacrylate) (PMMA) with PMMA loops, poly(hydroxyethyl methacrylate) (PHEMA) lenses, silicone lenses, and PMMA lenses with polypropylene loops were examined in this study. The concentrations of the activation peptides C3a, C4a and C5a were measured by radioimmunoassay (r.i.a.) in human serum after incubation with and without IOLs for up to 12 h. The presence of silicone lenses caused an increase in C3a levels. In the presence of polypropylene loops, the concentrations of both C3a and C5a were significantly higher than in serum incubated alone. There was no statistically significant increase in the concentration of C4a caused by any of the materials tested. The results suggest that IOLs made from silicone or lenses with polypropylene loops activate the complement system via the alternative pathway.


Lithium and the retina.
Recent interest in light therapy for depression has stimulated consideration of the nature of the biological defect in affective disorder. One line of thinking suggests that manic-depressive patients are supersensitive to light and that lithium may act by altering light sensitivity and hence entrainment of biological rhythms. This paper focuses on possible mechanisms whereby lithium may influence retinal physiology and the ability to perceive light. Preliminary data were generated using the Dark Adaptation Threshold procedure with a repeated measure protocol. When depressed and unmedicated the patient was found to have significantly lowered thresholds for light detection compared to control values. This supersensitivity was alleviated following lithium treatment. Data are interpreted as suggesting that some of the therapeutic effects of lithium are localized in the retina. It is proposed that: (1) lithium primarily alters the ability of the retina to detect light and not visual acuity; (2) lithium influences sensitivity to light by modulating the functional environment of the rod photoreceptors in the retina and (3) future research should focus on the effect of lithium on the function of rod photoreceptors and the pigmented epithelial cells in patients with affective disorder.


Diagnosis and management of isolated pancreatic tuberculosis: experience of 13 cases.
To analyze the diagnosis and treatment of pancreatic tuberculosis. Retrospectively reviewed and summarized 13 pancreatic tuberculosis patients' clinical information, presentation, diagnostic methods, therapeutic approaches, and prognosis from 1958 to 2004 at Peking Union Medical College Hospital. All cases presented a wide series of symptoms, including fever in 6 cases, upper abdominal tenderness in 13, epigastric mass in 4, obstructive jaundice in 3, night sweat in 4, weight loss in 7, hypersplenotrophy and hypersplenism in 1, and being complicated with tuberculosis of other organs in 3. One case was diagnosed by clinical symptoms and biopsy of lymph node, and only received anti-tubercular treatment Others were diagnosed by intra-operative biopsy and anti-tubercular treatment, and got well without recurrent tuberculosis in pancreas and other organs during 6 months to 2 years of follow-up. The non-operative case presented extrahepatic portal hypertension. Pancreatic tuberculosis may be considered in the patients with fever, abdominal tenderness, weight loss, and imaging evidence of regional pancreatic lesion. Efficacy of anti-tubercular agents and laparotomy for pancreatic tuberculosis is evident.


Hydroxyurea inhibition of growth and DNA synthesis in Toxoplasma gondii: characterization of a resistant mutant.
Hydroxyurea inhibited the growth and DNA synthesis of Toxoplasma gondii growing in human fibroblast cells. A concentration of 18 micrograms/ml totally suppressed plaque formation. The synthesis of T. gondii RNA was not acutely inhibited. The parasite was equally sensitive to hydroxyurea when grown in wild type or hydroxyurea resistant host cells. With the aid of chemical mutagenesis, we isolated a stable hydroxyurea resistant mutant of T. gondii. This mutant showed no increased ability to incorporate [3H]uracil into its pyrimidine deoxynucleotide pool. Hydroxyurea depressed the [3H]uracil labeling of the pyrimidine deoxynucleotide pool in the wild type parasite but not in the mutant, suggesting that the mutant ribonucleotide reductase was resistant to the inhibitory effect of the drug.


Dielectric analysis of yeast cell growth.
On-line dielectric measurements of yeast cells (Saccharomyces cerevisiae) growing in suspension culture were made over a frequency range from 0.1 to 100 MHz. The amplitude of the dielectric dispersion centered at about 1 MHz increased exponentially with cultivation time in the logarithmic growth phase and then remained constant in the stationary phase. This result clearly indicates that the mass and concentration of the yeasts can be monitored by the dielectric method. In the late logarithmic growth phase, a subdispersion appeared around 10 MHz, whose amplitude was less than 6% of that of the whole dispersion. The development of the subdispersion indicates the increase in the volume of the vacuole in the yeasts. In synchronized cell culture, the amplitude of the dispersion changed stepwise. The time interval between the steps was about 100 min. that corresponds to the generation time of the yeast.


Anatomy and Applications of the #15 Scalpel Blade and Its Variations.
Scalpels have been used to make skin incisions since the advent of "modern" dermatosurgery. #15 Scalpel blade and #3 handle (Bard-Parker handle) are most frequently used by a dermatosurgeon. Besides the proper equipment, appropriate technique is mandatory to ensure a "precise" incision. In this article, we discuss about the anatomy, variations, and different uses of the #15 scalpel blade and the ideal method of making a "precise" skin incision.


A comparison of the effects of fetal bovine serum and newborn calf serum on cell growth and maintenance of cryopreserved mouse spermatogonial stem cells.
Serum is a common supplement that is widely used to protect various cells and tissues from cryopreservation because it provides the necessary active components for cell growth and maintenance. In this study, we compared the effects of newborn calf serum (NCS) and fetal bovine serum (FBS) on the cryopreservation of mouse spermatogonial stem cells (SSCs). The isolated SSCs were cryopreserved in two groups: freezing medium that contained 10% DMSO (dimethyl sulfoxide) and 10% FBS in DMEM (Dulbecco's Modified Eagle's Medium) (group 1) and freezing medium that contained 10% DMSO and 10% NCS in DMEM (group 2). Real-time PCR was performed for stemness gene expression. The SSCs' viability was performed by trypan blue. We observed that the SSCs had increased viability in the NCS-freeze/thaw group (87.82%) compared to the FBS-freeze/thaw group (79.83%), but this increase was not statistically significant (P < 0.105). Promyelocytic leukemia zinc finger (Plzf) and Lin28 gene expression levels in the NCS-frozen/thawed SSCs were not significantly different compared to the FBS-frozen/thawed SSCs; however, Nanog gene expression increased considerably, and Dazl gene expression decreased significantly. The results in this study demonstrated that the presence of NCS in a solution of cryopreserved SSCs increased their viability after freeze/thawing and might promote the proliferation of cultivated SSCs in vitro by increasing the relative expression of Nanog.


Electromechanical association in regionally stunned swine myocardium.
Postischemic myocardial dysfunction ("stunned" myocardium) is a common problem after cardiac surgery and cardiac transplantation. A "low-voltage" QRS complex in the electrocardiogram is also often seen in patients with severe cardiac dysfunction. The authors investigated the relationship between mechanical function and electrographic characteristics in postischemic swine myocardium, and determined whether inotropic stimulation with dobutamine alters the electrogram while improving mechanical function. Regional wall thickening and regional electrogram from electrodes in the endo- and epicardium were measured in 12 pigs during intravenous infusion of several doses of dobutamine (1-25 micrograms.kg-1.min-1) before and after 10 or 15 min of ischemia followed by 1 h of reperfusion. Wall thickening was abolished after ischemia and reperfusion, and QRS amplitude decreased 25% in the endocardium and 29% in the epicardium. Dobutamine infusion restored both wall thickening and myocardial QRS amplitude to baseline values. The correlation between myocardial QRS amplitude and systolic wall thickening was significant in each animal (r = 0.88 +/- 0.02 (mean +/- 1 SEM, n = 12); median r = 0.89; range 0.74-0.95, P < 0.01, for all relations). This study showed a close association between local electrical and mechanical events in postischemic swine myocardium.


(Eta5-cyclopentadienyl)(p-fluorophenoxo)(nitrosyl)(trimethylsilylmethyl)molybdenum(II).
The title complex, [Mo(C(5)H(5))(C(6)H(4)FO)(C(4)H(11)Si)(NO)], is formed by reacting CpMo(NO)(CH(2)SiMe(3))(2), where Cp is cyclopentadienyl, with one equivalent of p-FC(6)H(4)OH. The complex exhibits the expected piano-stool molecular structure, with a linear nitrosyl ligand [Mo-N-O 168.2(2) degree] having Mo-N and N-O distances of 1.764(2) and 1.207(3)A, respectively. The phenoxo Mo-O distance of 1.945(2)A is suggestive of some multiple-bond character.


Bionomics of Aedes aegypti subpopulations (Diptera: Culicidae) from Misiones Province, northeastern Argentina.
Life statistics of four Aedes aegypti subpopulations from the subtropical province of Misiones were studied during autumn and winter, under semi-natural conditions, coming from the localities of Posadas (SW), San Javier (SE), Bernardo de Irigoyen (NE) and Puerto Libertad (NW). The eastern subpopulations are geographically separated by the central mountain system of the province from the western subpopulations. High percentages of larval and pupal survival (97-100%) were recorded, and no significant differences were detected among the four subpopulations. Larvae and pupae lasted approximately 8 days to complete their development, no significant differences being detected among the four subpopulations studied. Sex ratio recorded did not differ significantly from 1:1. Male longevity did not show difference among the different subpopulations, but female longevity was remarkably different among the four subpopulations (F=16.27; d.f.=(3;8); P=0.0009), ranging among 11.45 days for San Javier and 57.87 days for Posadas. Fecundity also varied considerably among subpopulations, the greatest number (307.44 eggs/female) being recorded for Posadas (F=4.13; d.f.=(3;8); P=0.04). Ae. aegypti females of the western subpopulations lived longer than the eastern subpopulations studied, therefore, the risk of dengue outbreak would be greater on the Misiones Province border with Paraguay.


Openings in frog microvascular endothelium at different rates of increase in pressure and at different temperatures.
Experiments were carried out on single mesenteric capillaries and venules of pithed frogs to determine whether the rate of increase in intravascular pressure (dP/dt) influenced the critical pressure (P(B)) which increases wall permeability. Vessels, microperfused with frog Ringer solutions containing 0.1% bovine serum albumin and red cells, were occluded downstream before pressure was raised either as a ramp or in a series of 13.6 cmH2O steps. By varying step duration, the mean dP/dt could be matched to dP/dt applied as a steady ramp. P(B) was recorded as the pressure at which there was an abrupt increase in filtration with red cells passing to and through one or more sites in the vessel wall. In all vessels, increasing dP/dt raised P(B), with no differences between steps and ramps. The relation between P(B) and dP/dt was linear, consistent with a latent period, T (the slope), between a critical pressure being reached and the abrupt increase in permeability being observed. Direct observation confirmed this latent period. Between 12 and 20 (o)C, T was 8.5 +/- 0.47 s; between 0 and 5 degrees C, T was 11.5 +/- 0.97 s. Tissue cooling did not influence the time constant, tau, describing the rate of stretch of wall following a step increase in pressure and used to measure wall visco-elastic properties. Nor was the value of tau (1.15 +/- 0.06 s, n = 42) consistent with T being accounted for by visco-elasticity. It is suggested that the latent period may indicate an active response of the endothelium.


Atmospheric wet deposition of trace elements in Bangladesh: A new insight into spatiotemporal variability and source apportionment.
The interaction between water vapor and natural/anthropogenic airborne particles deposits a massive amount of trace elements in the ecosystem. As the principal source region of the Indian monsoon originated from the Bay of Bengal, atmospheric trace elements in Bangladesh have impacted atmospheric wet deposition along the pathway, even reaching the headwaters in the Asian water tower. However, no study reports the atmospheric wet deposition of trace elements at the spatiotemporal scale. Thus, this study investigated the concentration, sources, and deposition of eighteen trace elements (Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Rb, Sr, Mo, Cd, Sn, Sb, Ba, and Pb) from 232 precipitation samples at four sites in Bangladesh. Results showed that the VWM concentrations of the eighteen measured trace elements ranged from 0.03 to 535.6 μg L-1. Zn, Fe, and Al were the principal elements of the atmosphere at four sites with mean values of 207.9 ± 227.8, 18.2 ± 9.3, and 16.3 ± 6.8 μg L-1, respectively. Besides, the eighteen trace elements showed significant variation in spatial scale with distinct seasonality. Enrichment factors of Zn, Sb, and Cd indicated serious anthropogenic influences. The major sources of trace elements were fossil fuel combustion, brick kilns, crustal dust, fugitive Pb, metal smelters, and battery recycling. Both the concentration and precipitation amount played a pivotal role in the deposition. Most of the air masses during the monsoon season came from marine sources passing over southern India and Sri Lanka. Meanwhile, the air masses during the non-monsoon season were from West Asia and the northwestern Indian subcontinent. The air masses are transported over a long range and deposit massive amounts of particulate matter in the Third Pole Himalayan region. This first-hand work on spatiotemporal variation provides a reference dataset for future targeting of the scientific community and policymakers for the development of strategies and action plans.


Relationships of substance use to attitudes toward gender roles, family and cohabitation.
This study utilizes data from four nationally representative subsamples of white high school seniors to analyze the relationships of alcohol consumption, marijuana use, and other illicit drug use to attitudes toward gender roles, family, and cohabitation. These analyses provide evidence concerning two hypotheses: the Gender Roles Hypothesis and Deviance Hypothesis. As predicted by the Gender Roles Hypothesis, among males, traditional gender role attitudes were associated with greater alcohol consumption. Contrary to the predictions of the Gender Roles Hypothesis, for females, nontraditional gender role attitudes were not associated with greater alcohol consumption or drug use in analyses which controlled for confounding factors such as family structure, socioeconomic status, and religiosity. As predicted by the Deviance Hypothesis, nontraditional attitudes toward cohabitation and family were associated with greater alcohol consumption and illicit drug use among both males and females.


Neurogenic inflammation is associated with development of edema and functional deficits following traumatic brain injury in rats.
The present study has used capsaicin-induced neuropeptide depletion to examine the role of neurogenic inflammation in the development of edema and functional deficits following traumatic brain injury (TBI). Adult, male rats were treated with capsaicin (neuropeptide-depleted) or equal volume vehicle (controls) 14 days prior to induction of moderate/severe diffuse TBI. Injury in vehicle treated control animals resulted in acute (4-5 h) edema formation, which was confirmed as being vasogenic in origin by diffusion weighted magnetic resonance imaging and the presence of increased permeability of the blood-brain barrier (BBB) to Evans blue dye. There was also a significant decline in brain magnesium concentration, as assessed by phosphorus magnetic resonance spectroscopy, and the development of profound motor and cognitive deficits. In contrast, capsaicin pre-treatment resulted in a significant reduction in post-traumatic edema formation (p < 0.001), BBB permeability (p < 0.001), free magnesium decline (p < 0.01) and both motor and cognitive deficits (p < 0.001). We conclude that neurogenic inflammation may play an integral role in the development of edema and functional deficits following TBI, and that neuropeptides may be a novel target for development of interventional pharmacological strategies.


Younger women with diminished oocyte reserve are not more prone to meiosis errors leading to spontaneous abortion than their age peers with normal oocyte reserve.
To determine the relative effect of age vs ovarian oocyte reserve on miscarriage rates. Miscarriage rates (loss of pregnancy established by ultrasound) from pregnancies achieved through in vitro fertilization-embryo transfer (IVF-ET) were evaluated according to four age groups (< or = 35, 36-39, 40-42, and 43-44 years) and four day 3 serum follicle-stimulating hormone (FSH) groups (< or = 11, 12-14, 15-17, and > 17 mIU/ml). All cycles were supplemented with progesterone in the luteal phase. With each advancing age group irrespective of the FSH levels, there was a progressive increase in miscarriage rates. In contrast, no difference in miscarriage rates were seen as FSH levels increased (and thus ovarian reserve decreased) in women up to 42 years of age. Only in the group aged 43-44 years was there an association with diminished oocyte reserve and miscarriage. Since low FSH stimulation protocols were purposely used for the group with diminished oocyte reserve, the data are consistent that the conclusion regarding poor oocyte quality in women with diminished oocyte reserve was mostly iatrogenic and related to the use of high-dosage FSH stimulation trying to create more oocytes for retrieval.


[Reflux esophagitis--morphology (author's transl)].
Comparative evaluation of the clinical and morphologic-histologic findings in reflux esophagitis led to the following staging; Stage I: Discrete leukocyte infiltrations of the tunica propria, and epithelial changes primarily of a hyperregenerative nature (noticeable only by histology). Stage II: macroscopic changes with erythematous stripes in the mucosa, which are shown histologically to be erosions or fibrinous necrosis; endoscopic feature: "white stripes." Stage III: deep, confluent necrosis with stenosis. This clinical-morphologic staging is a basis for therapy.


Immunological methods to quantify and characterize proteasome complexes: development and application.
The ubiquitin-proteasome pathway plays major roles in all aspects of biology and contributes to various disease processes. Due to the lack of assays that permit proteasome quantification in crude cell extracts, its concentrations in health and disease states as well as the relationship between free 20S core particles (20S) and 26S proteasomes (26S) that consist of 20S singly or doubly capped with 19S regulator complexes (19S) are still largely unknown. Thus, we established a 20S ELISA for the detection of total 20S, and developed a specific 26S ELISA. The latter utilizes the ATP/Mg2+ requirement for 26S stability and shows no cross-reactivity with 20S. Both ELISAs demonstrate intra- and inter-assay variations between 4.9% and 9.4% and recoveries of 105%-109%. Initial application showed that maintenance of the physiological ATP concentration is essential for accurate 26S assessment. Measurements in erythrocyte and peripheral blood mononuclear cell (PBMNC) extracts revealed that the concentrations of 20S were 15-fold and of 26S 130-fold higher in PBMNCs, and suggested that the 26S is the physiological relevant form in PBMNCs (molar ratio 20S/26S 1.1+/-0.4), whereas free 20S is predominant in erythrocytes (molar ratio 20S/26S: 11.5+/-4.0). During storage of packed red blood cell units spontaneous 26S assembly was detectable while specific 26S enzyme activities decreased, indicating that these assays are useful to assess the dynamic interplay between the 20S and 19S. During 26S assay development we further observed that solid phase affinity immobilization (SPAI) of 26S enables quantification of its dissociation into 20S and 19S. Utilizing the SPAI-26S method in combination with the non-hydrolyzable analogue ATP[beta,gamma-NH] and Mg2+ depletion, we provided evidence that ATP binding without hydrolysis via a high affinity binding site (Kd 4-6 microM) as well as ATP binding with hydrolysis via a low affinity binding site that is virtually not saturable under physiological conditions is required to fully stabilize the 26S. Application of these immunological techniques is expected to facilitate proteasome analyses, and may help to better understand its roles in health and disease processes.


Regulation of mu binding sites after chronic administration of antibodies directed against specific anti-opiate peptides.
There is some indication that anti-opiate peptides (AOP) modulate opioid receptor systems by altering mu-receptor density. To further characterize this phenomenon, we investigated the effects of continuous infusion of anti-AOP IgG on mu binding sites in the brains of rats. Specifically, male Sprague-Dawley rats received intracerebroventricular (i.c.v.) infusions for 13 days of either control (rabbit) IgG or test IgGs: anti-dynorphin A IgG, anti-dynorphin A1-8 IgG, anti-alpha-MSH IgG, or the monoclonal anti-NPFF IgG. Administration of anti-NPFF IgG or the anti-dynorphin1-8 IgG significantly increased mu labeling by 40-70% in several brain regions at the caudate level. Contrary to these findings, anti-alpha-MSH IgG decreased (19-32%) [125I]-DAMGO labeling in several thalamic nuclei. The results suggest that the density of mu-opioid receptors is regulated in part by anti-opiate peptides in the extracellular fluid of the brain.


Phosphoinositide 3-kinase inhibitors protect mouse kidney cells from cyclosporine-induced cell death.
The use of cyclosporine has been restricted by its nephrotoxic effects mediated, in part, by reactive oxygen species (ROS). Phosphoinositide 3-kinase, protein kinase B, and extracellular regulated kinase (ERK) pathways are related to survival and cell death and are activated after ROS generation. In this study, we evaluated the effects of cyclosporine on these pathways and their contribution to cyclosporine-induced toxicity. Viability of cells derived from the proximal tubule of transgenic mice was measured with Trypan Blue, ROS generation by a fluorescent probe, while ERK and phosphoinositide 3-kinase/protein kinase B activation were monitored with phospho-specific antibodies. Cyclosporine decreased cell viability and induced ROS generation and ERK and phosphoinositide 3-kinase activation. Both pathways were activated by the epidermal growth factor receptor (EGFR). Antioxidants blocked ERK activation but failed to inhibit protein kinase B phosphorylation or prevent cyclosporine toxicity. ERK inhibition did not protect from cyclosporine-induced cell death. EGFR or phosphoinositide 3-kinase inhibitors protected from cyclosporine-triggered cell death without decreasing ROS. Small interfering RNA against the catalytic subunit of phosphoinositide 3-kinase decreased protein kinase B phosphorylation but did not prevent cyclosporine-mediated cell death. Our results show that EGFR mediates the cytotoxic effects of cyclosporine through an ROS-independent mechanism. Cyclosporine-induced cell death is triggered by a non-classical phosphoinositide 3-kinase and does not require ERK activation.


Involvement of multiple protein kinase C isozymes in the ACTH secretory pathway of AtT-20 cells.
1. The mouse AtT-20/D16-16 anterior pituitary tumour cell line was used as a model system for the study of protein kinase C (PKC)-mediated enhancement of calcium- and guanine nucleotide-evoked adrenocorticotrophin (ACTH) secretion. 2. A profile of the PKC isozymes present in AtT-20 cells was obtained by Western blotting analysis and it was found that AtT-20 cells express the alpha, beta, epsilon and zeta isoforms of PKC. 3. PKC isozymes were activated by the use of substances reported to activate particular isoforms of the enzyme. The effects of these substances were investigated in both intact and electrically-permeabilized cells. Phorbol 12-myristate 13-acetate (PMA, EC50 = 1 +/- 0.05 nM, which activates all isozymes of PKC, except the zeta isozyme), thymeleatoxin (TMX, EC50 = 10 +/- 0.5 nM, which activates the alpha, beta and gamma isozymes) and 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA, EC50 = 3 +/- 0.5 nM, a beta 1-selective isozyme activator) all stimulated ACTH secretion from intact cells in a concentration-dependent manner. Maximal TMX stimulated ACTH secretion was of a similar degree to that obtained in response to PMA but maximal dPPA-stimulated ACTH secretion was only 60-70% of that obtained in response to PMA or TMX. 4. Calcium stimulated ACTH secretion from electrically-permeabilized cells over the concentration-range of 100 nM to 10 microM. PMA (100 nM), TMX (100 nM) but not dPPA (100 nM) enhanced the amount of ACTH secreted at every concentration of calcium investigated. PMA (100 nM) and TMX (100 nM)significantly enhanced ACTH secretion in the effective absence of calcium (i.e. where the free calcium concentration is nM).5. GTP-gamma-S stimulated ACTH secretion from permeabilized cells in a concentration-dependent manner with a threshold of 1 micro M. PMA (100 nM), TMX (100 nM) but not dPPA (100 nM) increased the amount of ACTH secretion evoked by every concentration of GTP-gamma-S investigated.6. The PKC inhibitor, chelerythrine chloride (10 micro M), blocked the PMA (100 nM)-evoked enhancement of calcium- and GTP-micro-S-stimulated ACTH secretion but did not significantly alter calcium- or GTP-micro-S-evoked secretion itself.7. The present paper indicates that AtT-20 cells express multiple isoforms of PKC and that these act at different sites in the secretory pathway for ACTH secretion. The alpha and epsilon isozymes of PKC can act distal to calcium entry to modulate the ability of increased cytosolic calcium concentrations to stimulate ACTH secretion. This site of action is either at the level of, or at some stage distal to, a GTP-binding protein which mediates the effects of calcium upon ACTH secretion. The beta isozyme of PKC may act ata stage early in the secretory pathway to regulate the cytosolic calcium concentration.


The effect of surgery and nutritional regimen on plasma lipoproteins and fat metabolites in man.
Plasma lipoproteins and fat metabolites were measured before and during the first five post-operative days in patients undergoing elective abdominal surgery of moderate severity. They received nutrition as total parenteral nutrition (TPN) or 4% dextrose saline (D S ) or isotonic aminoacids (IAA). Surgery caused an immediate fall in total and very low density lipoprotein triglyceride and total high density lipoprotein cholesterol but a rise in the high density lipoprotein subfraction 2 cholesterol. The increase in total triglyceride after 5 post-operative days was due principally to changes in triglyceride not carried by very low density lipoprotein and was related to the type of nutrition provided. There was no evidence of impaired intra-vascular lipolysis.


Phage evolution: new worlds of genomic diversity.
A recent comparative survey of genomes of phages infecting mycobacteria reveals a vast combinatorial network of gene rearrangements and may provide general models for pattern and process in genome evolution.


Potentiating the benefit of vascular-supplied glutamine during small bowel storage: importance of buffering agent.
Glutamine (gln)-supplemented University of Wisconsin (UW) solution improves overall small bowel (SB) preservation. Sustained gln metabolism in a system devoid of hepatic detoxification will necessarily result in the accumulation of pH active end products leading to nonphysiologic pH shifts. We hypothesized that simultaneous addition of N,N-bis[2-hydroxyethyl]-2-aminoethane sulfonic acid (BES), a known buffering agent, would potentiate the beneficial effect of gln supplementation by addressing the fundamental metabolic principle of pH homeostasis. Sprague-Dawley SB rats were administered a vascular flush with one of four solutions: UW; UW+90 mM BES (UWB); UW+2% gln (UWG); or UW+2% gln+90 mM BES (UWBG). Indices of energetics, barrier function, gln catabolism, and histology (light and electron microscopy) were assessed over a 10-hr cold storage time course. Superior gln utilization in the UWBG group was indicated by elevated levels of key catabolites (glutamate, aspartate, glycine, ammonia). The addition of BES and gln resulted in significantly higher levels of all energetic parameters (ATP, total adenylates) at 10 hr compared with UW, UWB, and/or UWG. Barrier function was markedly improved after 10 hr storage in the UWBG group; mannitol permeability was 169 nmol/cm2/hr versus 572 and 445 nmol/cm(2)/hr (for UW and UWG, respectively). Histologic injury at 10 hr was 5.5, 7.5, and 8 (Park's grade) for UWBG, UWG, and UW. Ultrastructural damage was markedly reduced with UWBG, as assessed by grade of mitochondria damage. This study strongly supports that the beneficial effects of gln-enriched UW solution can be amplified when combined with an effective buffering agent such as BES.


Ligand-Based and Structure-Based Virtual Screening of New Sodium Glucose Cotransporter Type 2 Inhibitors.
Diabetes mellitus is a metabolic disease that causes multiple complications and common comorbidities, which decreases the quality of life for people affected by the disease. Sodium glucose cotransporter type 2 (SGLT2) participates in the reabsorption of 90% of glucose in the kidneys; therefore, it is an attractive drug target for controlling blood glucose levels. The aim in this work was to obtain new potential SGLT2 inhibitors. A ligand-based virtual screening (LBVS) from the ZINC15, PubChem and ChemSpider databases using the maximum common substructure (MCS) scaffold was performed. A total of 341 compounds were obtained and analyzed by molecular docking on the active site of SGLT2. Subsequently, 15 compounds were selected for molecular dynamics (MD) simulation analysis. The compounds derived of spiroketal Sa1, Sa4, and Sa9 (≤ 3.5 Å) in complex with the receptor SGLT2 showed good stability during 120 ns of MD. These compounds are proposed as potential SGLT2 inhibitors.


A novel splice variant of the decapentaplegic (dpp) gene in the wild silkworm, Bombyx mandarina.
Decapentaplegic (dpp) is a member of the transforming growth factor-β superfamily. Although the dpp gene and related pathways are known to play important roles in insect development, few studies have examined its function in Bombyx mori and Bombyx mandarina. To date, there have been no previous reports on novel splice variants of dpp in silkworm. In the present study, we conducted RT-PCR to examine dpp expression in the mid-gut tissue of B. mandarina and discovered a novel dpp isoform. The isoform sequence was confirmed using sequencing analysis and found to have 333 bp deletion compared to full-length cDNA encoding dpp. The deleted sequence encodes a region of the latency associated peptide (LAP) region of transforming growth factor-β (TGF-β), which may affect the activity and specificity of TGF-β. Using variant calling analyses, we detected 7 candidate single nucleotide variants (SNVs) for different alternative splicing in dpp. This is the first report of a novel splice variant of the dpp gene in B. mandarina and these results provide insight about the domestication process and distinct phenotypic traits of B. mori and B. mandarina.


Techniques for Increasing Educational Motivation and the Need to Assess Students' Knowledge: The Effectiveness of Educational Digital Games in Learning English Grammatical Material.
Educational digital games can be an effective way to teach English grammatical material because they provide an interactive and engaging learning experience. The purpose of this study is to clarify how playing digital games affects students' motivation and performance in university-level English grammar classes. [The North-Eastern Federal Institute of MK Ammosova in Neryungri] used a quasi-experimental study, testing, respondent survey, and statistical data analysis method for this purpose. 114 Fourth-year students were the participants, and they were split into the experimental and control groups at random. Students in the experimental group were given a learning format that included the use of digital games designed to teach English grammar (Quizlet and Kahoot!). The traditional teaching strategies offered by the university curriculum were used with the students in the control group (written assignments, textbooks, presentations, and tests). The post-test revealed that the control group's results were nearly identical to those of the pre-test. The students in the experimental group performed better. The proportion of students scoring "poor" fell from 30 to 10%, while the proportion scoring "moderate" fell from 42 to 27%. The "good" score increased from 17 to 40%, and the "excellent" score increased from 11 to 23%. These results suggest that digital games are a more productive and effective tool for teaching English grammar than traditional games. Students were also highly motivated, as they found digital games to be both entertaining and effective for language acquisition. Academic performance did not significantly improve. Based on this, future research might create electives or courses that teach English grammar more successfully using gamification techniques. These results can also be used to guide future research in education, language acquisition, and modern technology.


Preoperative chemotherapy does not influence the number of evaluable lymph nodes in resected gastric cancer.
While it is suggested that more than 15 lymph nodes (LNs) should be evaluated for accurate staging of gastric cancer, LN yield in western countries is generally low. The effect of preoperative chemotherapy on LN yield in gastric cancer is unknown. The aim of the present study is to determine whether preoperative chemotherapy is associated with any difference in the number of LNs obtained from specimens of patients who underwent curative surgery for gastric adenocarcinoma. In 1205 patients from Memorial Sloan-Kettering Cancer Center (MSKCC) and 1220 patients from the Netherlands Cancer Registry (NCR) who underwent a gastrectomy with curative intent for gastric adenocarcinoma without receiving preoperative radiotherapy, LN yield was analyzed, comparing patients who received preoperative chemotherapy and patients who received no preoperative therapy. Of the 2425 patients who underwent a gastrectomy, 14% received preoperative chemotherapy. Median LN yields were 23 at MSKCC and 10 in the NCR. Despite this twofold difference in LN yield between the two populations, with multivariate Poisson regression, chemotherapy was not associated with LN yield of either population. Variables associated with increased LN yield were institution, female sex, lower age, total (versus distal) gastrectomy and increasing T-stage. In this patient series, treatment at MSKCC, female sex, lower age, total gastrectomy and increasing primary tumor stage were associated with a higher number of evaluated LNs. Preoperative chemotherapy was not associated with a decrease in LN yield. Evaluating more than 15 LNs after gastrectomy is feasible, with or without preoperative chemotherapy.


Social defeat stress in adult mice causes alterations in gene expression, alternative splicing, and the epigenetic landscape of H3K4me3 in the prefrontal cortex: An impact of early-life stress.
Chronic stress is the leading risk factor of a broad range of severe psychopathologies. Nonetheless, the molecular mechanisms triggering these pathological processes are not well understood. In our study, we investigated the effects of 15-day social defeat stress (SDS) on the genome-wide landscape of trimethylation at the 4th lysine residue of histone H3 (H3K4me3) and on the transcriptome in the prefrontal cortex of mice that were reared normally (group SDS) or subjected to maternal separation early in life (group MS+SDS). The mice with the history of stress early in life showed increased susceptibility to SDS in adulthood and demonstrated long-lasting genome-wide alterations in gene expression and splicing as well as in the H3K4me3 epigenetic landscape in the prefrontal cortex. Thus, the high-throughput techniques applied here allowed us to simultaneously detect, for the first time, genome-wide epigenetic and transcriptional changes in the murine prefrontal cortex that are associated with both chronic SDS and increased susceptibility to this stressor.


Reader variance in ROC studies--generalizability to reader population at high and low performance levels.
To investigate the variability between discriminative performances of readers as a function of average performance levels during receiver operating characteristic (ROC) studies. Four subsets of cases from previously ascertained ROC rating data by 12 observers when detecting interstitial disease and pneumothorax on posteroanterior chest films were selected for each abnormality and reanalyzed to assess changes in "reader" variance component. The subsets were selected based on a prestudy subjective assessment of the subtleness of depicted abnormality (positive cases) and the difficulty in determining its absence (negative cases). Reader variance component was estimated using a bootstrap approach for each subset and the results were used to assess a general relationship between variability and average performance level. The reader variance component decreased substantially (from 0.007704 to 0.000426), as expected, when the areas under the ROC curves (AUC) for detecting pneumothoraces increased from 84% to 97%. On the other hand, reader variance component increased substantially (from 0.000890 to 0.005181) when AUC for detecting interstitial disease increased from 59% to 87%. The large magnitude of and changes in the reader variance component resulted in a consistent nonmonotone relationship as a function of AUC when other related variance components were included in addition to the reader component. Among several factors affecting generalizability of ROC results to the population of readers, the reader variance component depended nonmonotonically on the average diagnostic performance and is lowest at both very high and very low levels of performance.


Effects of echo time on IVIM quantifications of locally advanced breast cancer in clinical diffusion-weighted MRI at 3 T.
The purpose of this study was to investigate the effects of echo time dependence in IVIM quantification of the pseudo-diffusion fraction in breast cancer and whether correcting for the echo time dependence offers added clinical value. Fifteen patients with biopsy-proven breast cancer underwent a 3 T MRI examination with an extended DWI protocol at two different echo times (TE = 53 ms, b = 0, 50 s/mm2 ; TE = 77 ms, b = 0, 50, 120, 200, 400, 700 s/mm2 ). Volumes of interest were delineated around the tumors. In addition, simulated MRI data were generated for different levels of signal-to-noise ratio and two values for the blood T2 relaxation time (T2p = 100 ms and 150 ms). The pseudo-diffusion signal fraction was estimated from the simulated and in vivo tumor data using both the standard IVIM model and an extended IVIM model that accounts for the echo time dependence arising from distinct transverse relaxation times. Simulations showed that the standard IVIM model overestimated the pseudo-diffusion fraction by 25% (T2p = 100 ms) and 60 % (T2p = 150 ms) (p < 0.0001 at SNR = 50). In vivo, the estimated apparent T2 value at b = 50 s/mm2 was around 8% lower than at b = 0 s/mm2 (p = 0.01) demonstrating a removal of the signal contribution from blood with long T2 associated with pseudo-diffusion. Using two different fixed values for T2p = 100, 150 ms, the pseudo-diffusion fraction was 15% and 46% higher in the standard model compared with the echo-time-corrected model (p < 0.01). The standard IVIM model was found to overestimate the pseudo-diffusion fraction by 15% to 46% compared with the echo-time-corrected model in breast tumor DWI data acquired at 3 T. Our results suggest that a corrected model may give more accurate results in terms of signal fractions, but may not justify the added time needed to acquire the additional data in terms of clinical value.


Novel three-dimensional coordination polymer of 2-(1,3,5-tri-aza-7-phospho-niatri-cyclo-[126.96.36.199,7]decan-7-yl)ethanoic acid with silver(I) tetra-fluoro-borate.
An AgI-based coordination polymer (CP), namely, poly[[[μ3-2-(1,3,5-tri-aza-7-phospho-niatri-cyclo-[220.127.116.11,7]decan-7-yl)ethano-ate-κ4 N:N':O,O']silver(I)] tetra-fluoro-borate], {[Ag(C9H16N3O2P)]BF4} n , was synthesized in an aqueous solution of zwitterionic 2-(1,3,5-tri-aza-7-phospho-niatri-cyclo-[188.8.131.52,7]decan-7-yl)ethan-o-ate (L) and AgBF4 with exclusion of light at room temperature. The colourless and light-insensitive CP crystallized in the monoclinic space group Cc. The asymmetric unit consists of an AgI cation, the zwitterionic L ligand and a BF4 - counter-ion. Each AgI ion is coordinated by two carboxyl-ate oxygen atoms in a chelating coordination mode, as well as one of the nitro-gen atoms of two neighbouring L ligands. The crystal structure of the CP was classified as a unique three-dimensional arrangement. The CP was also characterized in aqueous solutions by multinuclear NMR and HRMS spectroscopies and elemental analysis.


[Intraocular triamcinolone for diffuse diabetic macular edema].
The aim of the study was to evaluate the effect of an intravitreal injection of triamcinolone acetonide on the visual acuity of patients suffering from diffuse diabetic macular edema. The prospective, clinically interventional, uncontrolled study included 32 eyes (26 patients) with diffuse diabetic macular edema and received an intravitreal injection of 25 mg triamcinolone acetonide. Visual acuity was 0.12+/-0.08 (min.-max. 0.03-0.3; median 0.1) at baseline. Mean follow-up was 6.8+/-4.3 months. Visual acuity increased to 0.17+/-0.11 (min.-max.: 0.03-0.4; median 0.125) after 4 weeks (p=0.009) and reached a mean maximum of 0.20+/-0.14 (min.-max.: 0.03-0.5; median 0.16) after 8 weeks (p=0.006). Later, visual acuity showed a slow decrease, but was significantly higher than at baseline up to 6 months postoperatively and 26 eyes (81.3%) gained in visual acuity. Ten eyes (31.2%) developed steroid-induced secondary ocular hypertension. An intravitreal injection of 25 mg of triamcinolone acetonide may be an option in the treatment of diffuse diabetic macular edema.


[Ineffective atrial pacing and cardiac arrest in a 80-year old woman with hyperkalemia].
A case of 80-year-old woman with marked hyperkalemia in the course of chronic treatment with angiotensin converting enzyme (ACE) inhibitors and spironolactone is presented. AAI pacemaker was implanted three months ago. The ECG revealed a nodal rhythm, ineffective AAI pacing and other typical features of hyperkalemia. After normalisation of potassium level the ECG changes disappeared. Potential mechanism of the nodal rhythm during ineffective atrial pacing is discussed.


Effects of prior anterior cruciate ligament reconstruction on clinical outcomes associated with total knee arthroplasty: A protocol of retrospective analysis.
The argument on the clinical effects of previous anterior cruciate ligament (ACL) reconstruction on total knee arthroplasty (TKA) remains to be resolved. The aim of the current study was to compare operative and postoperative outcomes of patients undergoing TKA after ACL reconstruction with a matched cohort of control subjects having primary osteoarthritis and no history of ligament reconstruction. This study was performed and reported in accordance with the Strengthening the Reporting of Observational studies in Epidemiology checklist. The institutional review board approval of our hospital was obtained for the study. The ACL and control groups were matched 1:1 using a caliper width of 0.1 for the propensity score through nearest neighbor matching. Written informed consent was obtained from all subjects participating in the trial. The primary outcome measure was postoperative complications. Secondary outcome measures included operative time, tourniquet time, intraoperative complications, Oxford Knee Score, range of motion, and Western Ontario and McMaster Universities index. This study had limited inclusion and exclusion criteria and a well-controlled intervention. We hypothesized that prior ACL reconstruction had a negative impact on the operative and postoperative outcomes of TKA. This study protocol was registered in Research Registry (researchregistry5598).


Spinning the web of cell fate.
Spatiotemporal changes in nuclear lamina composition underlie cell-type-specific chromatin organization and cell fate, suggesting that the lamina forms a dynamic framework critical for genome function, cellular identity, and developmental potential.


Inhibition of phagocyte chemotaxis by uteroglobin, an inhibitor of blastocyst rejection.
Uteroglobin, a steroid-dependent secretory protein first discovered in the rabbit uterus during early pregnancy, is a potent phospholipase A2 inhibitor. We found that uteroglobin also inhibited human and rabbit phagocyte chemotaxis in response to formyl peptide attractants in a dose-dependent manner. Half-maximal inhibition was at 1.2 microM. Uteroglobin did not compete with a formyl peptide for its receptor but inhibited internalization of radiolabeled formyl peptide. Uteroglobin appears to inhibit chemotaxis by a mechanism different from that of dansylcadaverine, a well studied inhibitor of endocytosis. Unlike dansylcadaverine, uteroglobin did not have any effect upon the synthesis of phosphatidylcholine or phosphatidylinositol. It is suggested that uteroglobin may protect trophoblastic cells from the defense system of the host not only by binding to antigenic determinants of embryonic cells but also by impairing migration of phagocytes, one of the primary components of the immune defense system. These results may explain why embryonic cells do not elicit an inflammatory response in the uterine endometrium during pregnancy.


Light and temperature affect retinyl ester hydrolase activity and visual pigment composition.
Dim light, in combination with high water temperature, resulted in a significant increase in the retinyl ester hydrolase activity in the goldfish retina. This rise in enzyme activity may relate to a selective increase in the availability of retinal chromophores thereby favoring the formation of rhodopsin under these light and temperature conditions.


Dynamic exercise echocardiography in children with congenital heart disease affecting the left heart.
Thirty-five children (male 22, female 13) with congenital heart disease resulting in volume and pressure overload of the left ventricle were investigated echocardiographically during supine bicycle exercise. The children had to follow a test-protocol with increasing workload. Left ventricular function parameters were measured from M-mode-echocardiography, electrocardiography and phonocardiograms before, during and after exercise and were expressed as fractional shortening (FS), velocity of circumferential fiber shortening (VcF) and the frequency corrected parameters: FScorr. = FS X 100/HR and VcFcorr. = VcF X 100/HR (HR = heart rate). The data of this group of children under study were compared to those obtained from 140 healthy children examined under similar conditions. In children with pressure overload, values for fractional shortening, velocity of circumferential fiber shortening and the frequency corrected parameters were significantly higher than in normals throughout exercise testing. In some children with moderate to severe aortic stenosis or coarctation the frequency corrected parameters showed a decrease at higher exercise levels instead of an increase as seen in the majority of cases. In these cases cardiac output was increased by an abnormal rise in heart rate. This was considered as a diminished left ventricular reserve. After aortic valve replacement in two cases with aortic stenosis, parameters of left ventricular function were still elevated at rest and during exercise testing. In two children with hypertrophic cardiomyopathy the almost maximally elevated rest values did not change during exercise. In children with mild volume overload (small ventricular septal defect or aortic incompetence) the left ventricular function parameters were within the normal range or slightly below.


How variation in predictor measurement affects the discriminative ability and transportability of a prediction model.
Diagnostic and prognostic prediction models often perform poorly when externally validated. We investigate how differences in the measurement of predictors across settings affect the discriminative power and transportability of a prediction model. Differences in predictor measurement between data sets can be described formally using a measurement error taxonomy. Using this taxonomy, we derive an expression relating variation in the measurement of a continuous predictor to the area under the receiver operating characteristic curve (AUC) of a logistic regression prediction model. This expression is used to demonstrate how variation in measurements across settings affects the out-of-sample discriminative ability of a prediction model. We illustrate these findings with a diagnostic prediction model using example data of patients suspected of having deep venous thrombosis. When a predictor, such as D-dimer, is measured with more noise in one setting compared to another, which we conceptualize as a difference in "classical" measurement error, the expected value of the AUC decreases. In contrast, constant, "structural" measurement error does not impact on the AUC of a logistic regression model, provided the magnitude of the error is the same among cases and noncases. As the differences in measurement methods between settings (and in turn differences in measurement error structures) become more complex, it becomes increasingly difficult to predict how the AUC will differ between settings. When a prediction model is applied to a different setting to the one in which it was developed, its discriminative ability can decrease or even increase if the magnitude or structure of the errors in predictor measurements differ between the two settings. This provides an important starting point for researchers to better understand how differences in measurement methods can affect the performance of a prediction model when externally validating or implementing it in practice.


Putative sense organs on the pallial tentacles of the limpet, Patella vulgata (L.).
The structure and ultrastructure of ciliary tufts on the pallial tentacles of the limpet Patella vulgata (L.) are described. The tip of each tentacle is covered by a dense crown of tufts and additional tufts can be seen scattered evenly across the surface of each tentacle. The cilia are nonmotile and nerve fibres run from the base of the ciliated cells suggesting a sensory function. Comparisons are made with ciliary tufts found in a Pacific species of limpet, Acmaea scutum, and other molluscan sensory structures.


An analysis of the relative frequencies of reported adverse events associated with NSAID administration in dogs and cats in the United Kingdom.
This study aimed to analyse UK pharmacovigilance data to quantify adverse events (AEs) associated with the non-steroidal anti-inflammatory drug (NSAID) molecules found in veterinary medicines authorised for use in dogs and cats. It was hypothesised that the frequency of AEs would be lower when associated with cyclo-oxygenase-2 selective (coxib), compared to non-selective (non-coxib) NSAIDs. The UK Veterinary Medicines Directorate (VMD) supplied frequencies of AEs derived from Periodic Safety Update Reports subdivided by formulation and species for each NSAID molecule. Frequencies of AEs were similar between species. The five most reported AEs were emesis, death, anorexia, lethargy, and diarrhoea. Reported frequency of emesis, renal insufficiency and death was higher with injectable compared to oral NSAIDs (P = 0.043). Reported frequency of emesis, lethargy and death was higher with coxib, compared to non-coxib NSAIDs (P = 0.029). Median (range) interval since authorisation was shorter for coxibs at 5 (2.5-9) years compared to non-coxibs at 15 (12-25) years. A negative correlation between time elapsed since authorisation and the frequency of AEs was identified (rs = -0.11 to -0.94). Higher frequency of reported AEs with injectable NSAIDs may be related to perioperative administration. The AE frequency associated with coxib and non-coxib NSAIDs may be confounded by changes in reporting habits over time. This study highlights the value of interrogating passive surveillance data to identify low frequency AEs and the need to facilitate improvement in recording and collecting AEs in small animal practice.


Efficacy of Insulin Pump Therapy on Diabetes Treatment Satisfaction and Glycemic Control Among Patients with Type 1 Diabetes Mellitus in Saudi Arabia: A Prospective Study.
The aim of this study was to explore the impact of insulin pump therapy on diabetes treatment satisfaction and glycemic control among patients with type 1 diabetes mellitus (T1DM) in Saudi Arabia. A 6-month, prospective study was conducted among 47 patients (aged 17-24 years) with T1DM who attended the Insulin Pump Clinic at Prince Sultan Military Medical City, Riyadh, Saudi Arabia, between April 2014 and November 2014. The respondents were purposively and conveniently selected and were interviewed using the Arabic version of the Diabetes Treatment Satisfaction Questionnaire at baseline, 3, and 6 months. Demographics and clinical variables including hemoglobin A1c (HbA1c) were also collected. The mean (±standard deviation) age of the study cohort was 19.1 ± 1.93 years. Seventeen patients were male (36.2%) and 30 were female (63.8%). Compared to baseline, significant positive differences were found in treatment satisfaction among female patients and patients with long-standing T1DM at 6 months. Frequency of hyperglycemia and hypoglycemia declined significantly in female patients at 6 months and in patients who had a shorter duration of T1DM. Furthermore, significant positive differences were found in HbA1c levels among female patients and among those who had a shorter duration of T1DM compared to baseline. Both female and male patients and those with a shorter duration of T1DM showed a significant decline in insulin necessity at 6 months when compared to baseline. Although multiple daily injections is a feasible preference for insulin supply, insulin pumps should also be considered for patients with T1DM as it appears to increase patients' treatment satisfaction, decrease the frequency of hypoglycemia, hyperglycemia, and reduce HbA1c levels.


Late-Stage Diversification of Biologically Active Molecules via Chemoenzymatic C-H Functionalization.
Engineered variants of rebeccamycin halogenase were used to selectively halogenate a number of biologically active aromatic compounds. Subsequent Pd-catalyzed cross-coupling reactions on the crude extracts of these reactions were used to install aryl, amine, and ether substituents at the halogenation site. This simple, chemoenzymatic method enables non-directed functionalization of C-H bonds on a range of substrates to provide access to derivatives that would be challenging or inefficient to prepare by other means.


Draft Genome Sequence of Isolate Staphylococcus aureus LHSKBClinical, Isolated from an Infected Hip.
We report here the genome sequence of a clinical isolate of Staphylococcus aureus from an orthopedic infection. Phenotypically diverse Staphylococcus aureus strains are associated with orthopedic infections and subsequent implant failure, and some are highly resistant to antibiotics. This genome sequence will support further analyses of strains causing orthopedic infections.