Dollars and sense--the benefits of membership in the American Urological Association.
To enumerate some of the benefits of being a member in the American Urological Association (AUA) and to request support in promoting membership in our specialty society's parent organization (AUA). The benefits of belonging to a medical specialty society are assessed by weighing the costs of membership (financial expenditures, time constraints, society requirements, etc.) against the return one receives (scientific and educational benefit, collegiality, collectively bargained compensation, etc.). From a socioeconomic point of view, many of the benefits cannot be quantified; however, they are real and undoubtedly contribute in a variety of ways to the satisfaction of day-to-day practice. Financial incentives can be quantified, and present times dictate that they be enumerated. Additionally AUA proactively supports the livelihood of its members. Both financial incentives and financial gains are presented. Membership in AUA continues to be a bargain and the dollars and sense of belonging to AUA represent genuine and unparalleled value.


Spatial-Temporal Variations in Parasitological Prevalence and Host-Related Risk Factors of Camel Trypanosomiasis and Its Vectors in North Eastern Kenya: A Repeated Cross-Sectional Study.
Camel trypanosomiasis (Surra) is endemic in the Horn of Africa. Understanding the spatiotemporal variations in Surra prevalence, vector dynamics, and host-related risk factors is important in developing effective control strategies. A repeated cross-sectional study was conducted to determine the Surra parasitological prevalence, livestock reservoirs, vector density/diversity, and host-related risk factors in Kenya. Random samples of 847, 1079, and 824 camels were screened at the start of the dry season, peak dry season, and during the rainy season, respectively. Blood samples were examined using the dark ground/phase contrast buffy-coat technique, and Trypanosoma species were identified based on their movement and morphology in wet and stained thin smears. Reservoir status for Trypanosoma evansi was assessed in 406 cattle and 372 goats. A rainy and dry seasons entomological surveys were conducted to determine the Surra vector abundance/diversity and spatiotemporal density changes. Surra prevalence was 7.1%, 3.4%, and 4.1% at the start of the dry season, peak dry season, and rainy season, respectively. Camel co-infections by Trypanozoon (T. evansi or Trypanosoma brucei brucei) and Trypanosoma vivax were recorded. Spatial variations in Surra prevalence were recorded at the beginning of dry (X (7, N = 846) 2 = 110.9, p ≤ 0.001), peak dry (X (7, N = 1079) 2 = 42.2, p ≤ 0.001), and rainy (X (7, N = 824) 2 = 29.1, p ≤ 0.001) seasons. The screened cattle and goats tested negative for Trypanozoon (T. evansi or T. b. brucei), while two cattle tested positive for Trypanosoma congolense. Biting fly catches were composed of a single species from Tabanus, Atylotus, Philoliche, Chrysops, and Stomoxys genera. The total catches for Philoliche, Chrysops, and Stomoxys were higher in the rainy than dry season consistent with the prevalence results. Surra remains an important camel disease in the region with its prevalence varying in space and time. Camel co-infections by Trypanozoon (T. evansi or T. b. brucei) and T. vivax necessitate proper diagnosis of suspected cases and targeted therapy.


Localisation of the insulin-sensitive phosphatidylinositol glycan at the outer surface of the cell membrane.
A phosphatidylinositol-glycan has been implicated in the mechanism of action of insulin. Some of the actions of insulin may be mediated by the generation of the polar head group of this phosphatidylinositol-glycan. Localisation of the insulin-sensitive phosphatidylinositol-glycan was investigated by reacting the glycophospholipid with the imidoester [1-14C]-isethionyl acetimidate. The present results indicate that most of the insulin-sensitive phosphatidylinositol-glycan is localized at the plasma membrane of rat liver, being 85% of the glycophospholipid present at the outer surface of the cell. These results suggest a paracrine action of insulin.


Microscopic observation of human hairs infected with Microsporum ferrugineum.
Human hairs infected with Microsporum ferrugineum were examined by light and scanning electron microscopy to obtain information on the parasitic form. The fungus invaded the hair filaments and developed hyphae between the hair cuticles and cortex. Spheroids of arthroconidia were frequently observed to invade the hair follicle. A mosaic sheath of massive spheroids was observed around the hair filaments. The smooth-walled arthroconidia with chitinous surfaces were single, spherical or subspherical particles of 2.0-2.5 X 2.5-3.5 microns, and 2-celled, gourd-shaped (constricted at the septum) particles of 2.5-3.0 X 5.0-7.0 microns.


PC3, but not DU145, human prostate cancer cells retain the coregulators required for tumor suppressor ability of androgen receptor.
Androgen receptor (AR) functions in normal prostate epithelium as a tumor suppressor to inhibit continuous proliferation of these cells. Such tumor suppressor function of AR is lost in androgen depletion independent (ADI) prostate cancers. In type-I ADI cancers AR is not expressed, while in type-II ADI cancers AR is recaptured as an oncogene. The PC3 and DU145 human prostate cancer cell lines are representative of the earlier type-I ADI prostate cancers. While these cells do not express AR, it is unclear whether they retained the coactivators necessary for AR-dependent tumor suppression. To answer this question the response to AR protein expression by PC3 and DU145 cells was evaluated. To do this, a lentiviral AR (Lenti-AR) expression system was engineered to encode an AR transcript which includes appropriate 5' and 3' untranslated regions (UTRs) containing all previously identified post-transcriptional regulatory sequences. AR expression and transcriptional activity were evaluated in Lenti-AR transduced cells by Western blot and luciferase assay, respectively. Cell growth in culture and in mouse xenografts was evaluated in correlation to expression changes in p21, p27, and p45(SKP2) proteins. Lenti-AR transduced PC3 and DU145 lines expressed transcriptionally functional AR protein at appropriate physiological levels. Expression and engagement of AR protein in PC3-Lenti-AR cells resulted in transactivation of p21 and subsequent growth inhibition of these cells in culture and in mouse xenografts. Such inhibition was due to induced G1 arrest of these cells as documented by expression changes in p27 and p45(SKP2) proteins. Such growth inhibition was not observed in DU145-Lenti-AR cells. These results document that PC3, but not DU145 cells retain the coregulators needed for AR tumor suppressor ability.


Relation of spasms and myoclonus to suppression-burst on EEG in epileptic encephalopathy in early infancy.
This study was intended to clarify the relation between spasms in series and a suppression-burst (SB) EEG pattern which have a common nature of repetitive bursting activity in epileptic encephalopathy in early infancy. The ictal EEG traces of spasms were temporally compressed and expanded to study the beginning and ending phases of series along with their spectral analysis in two patients with Ohtahara syndrome (OS) and one with early myoclonic encephalopathy (EME). The EEG bursts associated with myoclonus were also investigated. A mutual transition was indicated between the ictal activity of spasms and the bursts in the peri-series SB on EEG. Gamma rhythm was detected in common in the ictal activity and the peri-series and interictal bursts on EEG, and also in the bursts with myoclonus. The relation between the ictal activity of spasms and SB on EEG was shown to be close. The generative mechanisms of spasms and myoclonus might be linked to the bursting tendency intrinsic to immature brain function.


Commercial Air And High-Altitude Travel by Pregnant Women: A scientific review commissioned by the European Board and College of Obstetrics and Gynaecology (EBCOG).
Air travel and long distance travel may have adverse effect on the pregnancy-induced physiology and these effects are more marked among those with pre-existing medical conditions. There are significantly increased risks of deep venous thrombosis, inflight transmission of infections, preterm labour, and other significant obstetric and medical complications that may be exacerbated by the flight and may require emergency care. Transient changes in cardiotocographic tracings during third trimester of pregnancy have been reported following air travel. It has been suggested that pregnant members of the flight crew may be at a slightly higher risk of spontaneous miscarriages. There are no contra-indications for healthy pregnant women on air travel. Those with underlying medical conditions should only embark on long distance travel following consultation with their obstetrician. Pregnant women should be advised to familiarise themselves with the healthcare system in the country/region they will be visiting and draw up an emergency plan of how they will contact the healthcare system at their destination.


P300 amplitude during a monetary incentive delay task predicts future therapy completion in individuals with major depressive disorder.
Treatment effectiveness for major depressive disorder (MDD) is often affected by client non-adherence, dropout, and non-response. Identification of client characteristics predicting successful treatment completion and/or response (i.e., symptom reduction) may be an important tool to increase intervention effectiveness. It is unclear whether neural attenuations in reward processing associated with MDD predict behavioral treatment outcome. This study aimed to determine whether blunted neural responses to reward at baseline differentiate MDD (n = 60; 41 with comorbid anxiety) and healthy control (HC; n = 40) groups; and predict MDD completion of and response to 7-10 sessions of behavior therapy. Participants completed a monetary incentive delay (MID) task. The N200, P300, contingent negative variation (CNV) event related potentials (ERPs) and behavioral responses (reaction time [RT], correct hits) were quantified and extracted for cross-sectional group analyses. ERPs and behavioral responses demonstrating group differences were then used to predict therapy completion and response within MDD. MDD exhibited faster RT and smaller P300 amplitudes than HC across conditions. Within the MDD group, treatment completers (n = 37) exhibited larger P300 amplitudes than non-completers (n = 21). This study comprises secondary analyses of EEG data; thus task parameters are not optimized to examine feedback ERPs from the paradigm. We did not examine heterogenous presentations of MDD; however, severity and comorbidity did not influence findings. Previous studies suggest that P300 is an index of motivational salience and stimulus resource allocation. In sum, individuals who deploy greater neural resources to task demands are more likely to persevere in behavioral therapy.


Smallest molecular chalcogenidometalate anions of the heaviest metals: syntheses, structures, and their interconversion.
The syntheses of the first molecular meta-selenidomercurate(ii), ortho-telluridothallate(iii) and a hydrate of an ortho-selenidoplubate(iv) are presented alongside an improved and facile synthesis of the selenidobismuthate(iii) with almost quantitative yields. By means of quantum chemical calculations, the energetics of the interconversions of small metalate anions is discussed and the existence of the heaviest homologues of [NO2](-), [NO3](-), [PO4](2-) and [CO3](2-) are predicted.


Effectiveness and safety of a management protocol to correct over-anticoagulation with oral vitamin K: a retrospective study of 1,043 cases.
Timely reversal of excessive anticoagulation is important in preventing bleeding complications. The use of vitamin K in correcting over-anticoagulation is widely accepted to be superior to discontinuation of therapy but its effectiveness and safety in large scale cohort studies has not been assessed. According to our protocol, 2 mg of oral vitamin K in addition to omitting the day's dose of warfarin, were administered to all patients presenting INR levels >or=5.0 and below 10.0; the INR values were checked 20 h after vitamin K administration. The rate of decay of INR, bleeding and thromboembolic complications at presentation and the following 30 days, as well as resistance to warfarin were assessed. Of the 1,611 events, 1,043 (878 patients) met the selection criteria. The median (interquartile range) INR was 6.64 (6.12-7.52) at presentation (day zero) and fell to a median (interquartile range) INR of 2.72 (2.18-3.52, P < 0.0001) after the vitamin K administration (day one) and 90.6% of the INRs were below 4.5. In 98 (9.4%) instances the INR values did not fall below the safe limit of 4.5 and in 173 (17%) instances the INR values were overcorrected to below 2.0. Median INR value on day zero in these two groups was higher (7.3 vs. 6.6, P < 0.0001) and lower (6.5 vs. 6.7, P = 0.049) than that of the remaining cases, respectively. Overcorrection occurred more frequently in women (P = 0.0002). Female gender was an independent factor associated with INR overcorrection (P = 0.001; OR = 1.7, 95% CI 1.3-2.3). The INRs on day one were inside, above and below the therapeutic range in 44%, 36% and 20% respectively. Warfarin resistance was observed in six cases (0.6%). Major bleeding was reported in one case (1.1 per 100 patient-years), minor bleeding in 14 cases (16.1 per 100 patient-years) and thromboembolic events in six high risk patients (6.9 per 100 patient-years) during the one month period following vitamin K administration. This adopted protocol for the reversal of excessive anticoagulation in asymptomatic or minor symptom presenting patients is easily applied, effective in lowering the INR and preventing complications. Its use in high risk thromboembolic patients warrants caution.


Plasma brain-derived neurotrophic factor in women after bariatric surgery: a pilot study.
Eighteen morbidly obese women had plasma brain-derived neurotrophic factor (BDNF) measured before bariatric surgery and 3 months postoperatively. We analyzed plasma BDNF levels in all the participants then subdivided according to menopausal status and type of surgery. Brain-derived neurotrophic factor decreased significantly in all the participants and in the premenopausal group when looked at in isolation.


Characterization of the internal IRES element of the zebrafish connexin55.5 reveals functional implication of the polypyrimidine tract binding protein.
Connexin55.5 (Cx55.5) is a gap junction protein with horizontal cell-restricted expression in zebrafish accumulating at dendritic sites within the receptor-horizontal cell complex in form of hemichannels where light-dependent plasticity occurs. This connexin is the first example of a gap junction protein processed to form two protein isoforms from a monocistronic message by an IRES mediated process. The nuclear occurrence of a carboxy-terminal fragment of this protein provides evidence that this gap junction protein may participate in a putative cytoplasmic to nuclear signal transfer. We characterized the IRES element of Cx55.5 in terms of sequence elements necessary for its activity and protein factor(s), which may play a role for its function. Two stretches of polypyrimidine tracts designated PPT1 and PPT2 which influence the IRES activity of this neuronal gap junction protein were identified. Selective deletion of PPT1 results in an appreciable decrease of the IRES activity, while the deletion of PPT2 results in a complete loss. RNA-EMSA and UV-cross linking experiments showed that protein complexes bind to this IRES element, of which the polypyrimidine tract binding protein (PTB) was identified as one of the interacting partners with influence on IRES activity. These results indicate that PTB conveys a role in the regulation of the IRES activity of Cx55.5. Our findings indicate that the activity of the IRES element of the neuronal gap junction protein Cx55.5 is subject of regulation through flanking polypyrimidine tracts, and that the non-canonical trans-activation factor PTB plays an essential role in this process. This observation is of considerable importance and may provide initial insight into molecular-functional relationships of electrical coupling in horizontal cells.


Subtypes of self-esteem and self-concept in adolescent violent and property offenders.
To investigate the relationship between subtypes of self-esteem/self-concept (familial, academic, social, and personal security) and antisocial behavior in adolescents (violent and property offending). A self-report survey was administered in a representative group of 1466 students aged 12 to 18. Both low family acceptance and low academic competence were found to predict property and violent offending, while high peer popularity was found to predict mainly violent offending. The finding that subtypes of self-esteem/self-concept present differently in antisocial adolescents may have clinical and scientific consequences, and such differentiation should be considered in future research. It should also be investigated whether this finding has therapeutic consequences.


A new in vitro injury model of mouse neurons induced by mechanical scratching.
The mixed culture of neurons and glial cells has been widely used as a mechanical insult model for the study of neuron injury in vitro. However, a better model is desirable to eliminate the interference of glial cells during the study. Here we report a new model with exclusive cerebellar granule neurons (CGNs), which can be used for the study of in vitro neuron injury without involvement of glial cells. We found that after scratching insult, there was a decrease in both the survival rate and vitality of injured CGNs. Meanwhile, pathological changes were observed by electron microscopy. With this new model, we also tested the effects of neurotrophin-3 (NT-3) on neuroprotection. The result showed that the vitality of injured CGNs was enhanced by the administration of NT-3. These findings demonstrate that this new model is useful for investigation of the precise effect of mechanical damage on neurons excluding other factors, and to detect the neuroprotective effect of certain factors on mechanically injured neurons.


Mini-LED, Micro-LED and OLED displays: present status and future perspectives.
Presently, liquid crystal displays (LCDs) and organic light-emitting diode (OLED) displays are two dominant flat panel display technologies. Recently, inorganic mini-LEDs (mLEDs) and micro-LEDs (μLEDs) have emerged by significantly enhancing the dynamic range of LCDs or as sunlight readable emissive displays. "mLED, OLED, or μLED: who wins?" is a heated debatable question. In this review, we conduct a comprehensive analysis on the material properties, device structures, and performance of mLED/μLED/OLED emissive displays and mLED backlit LCDs. We evaluate the power consumption and ambient contrast ratio of each display in depth and systematically compare the motion picture response time, dynamic range, and adaptability to flexible/transparent displays. The pros and cons of mLED, OLED, and μLED displays are analysed, and their future perspectives are discussed.


Signal-on electrochemical assay for label-free detection of TdT and BamHI activity based on grown DNA nanowire-templated copper nanoclusters.
Electrochemical methods allow fast and inexpensive analysis of enzymatic activity. Here, a simple and yet efficient "signal-on" electrochemical assay for sensitive, label-free detection of DNA-related enzyme activity was established on the basis of terminal deoxynucleotidyl transferase (TdT)-mediated extension strategy. TdT, which is a template-independent DNA polymerase, can catalyze the sequential addition of deoxythymidine triphosphate (dTTP) at the 3'-OH terminus of single-stranded DNA (ssDNA); then, the TdT-yield T-rich DNA nanowires can be employed as the synthetic template of copper nanoclusters (CuNCs). Grown DNA nanowires-templated CuNCs (noted as DNA-CuNCs) were attached onto graphene oxide (GO) surface and exhibited unique electrocatalytic activity to H2O2 reduction. Under optimal conditions, the proposed biosensor was utilized for quantitatively monitoring TdT activity, with the observed LOD of 0.1 U/mL. It also displayed high selectivity to TdT with excellent stability, and offered a facile, convenient electrochemical method for TdT-relevant inhibitors screening. Moreover, the proposed sensor was successfully used for BamHI activity detection, in which a new 3'-OH terminal was exposed by the digestion of a phosphate group. Ultimately, it has good prospects in DNA-related enzyme-based biochemical studies, disease diagnosis, and drug discovery. Graphical Abstract Extraordinary TdT-generated DNA-CuNCs are synthesized and act as a novel electrochemical sensing platform for sensitive detection of TdT and BamHI activity in biological environments.


Prevalence of mitral annular calcification and its association with mitral valvular disease.
Mitral annular calcification (MAC) is increasingly observed in elderly population. The purpose of this study was to investigate incidence of MAC and its association with mitral valvular disease (MVD). A total of 13,483 consecutive patients who underwent echocardiography were enrolled. MAC was defined as an echo-dense, shelf-like structure with an irregular, lumpy appearance involving the mitral valve annulus, with acoustic shadowing. Prevalence of MAC and its association with significant mitral stenosis (MS) or mitral regurgitation (MR) were studied. Significant (≥moderate) MS was defined as mean transmitral valvular pressure gradient > 5 mm Hg and significant MR was defined as ≥moderate MR based on quantitative or semi-quantitative Doppler methods. MAC was present in 1881 of 13,483 patients (14%). Patients with MAC (MAC group) was older and more female gender than those without MAC (non-MAC group). Significant MS was present in 2.2% of MAC and in .6% of the non-MAC group (p < 0.0001). Significant MR was present in 11.9% of MAC and in 5.0% of the non-MAC group (p < 0.0001). Co-existence of MAC and aortic valve replacement (AVR) was associated with increased prevalence of MVD (MS:11.4%, MR:17.2%, respectively). MAC was present in 14% of the patients and was associated with significant MVD. Co-existence of MAC and AVR may increase the risk of MVD.


Malignant epithelioid neoplasm of the ileum with ACTB-GLI1 fusion mimicking an adnexal mass.
Malignant epithelioid neoplasm with ACTB-GLI1 fusion are considered different from the more common pericytic lesions, such myopericytoma, because they have a spectrum of different genetic abnormalities. They appear to pursue a benign clinical course in young adults, although in sporadic cases lymph node metastasis were described. The categorization of this new type of tumor may also lead to new therapeutic strategies, because they might be sensitive to SHH pathway inhibitors. The case involves a 72-years-old multiparous woman who accessed our department after an incidental finding of a right adnexal mass of 43 mm with contrast-enhancement on a control computed tomography scan made for suspected diverticulitis. Our intervention was a detailed ultrasound description of the suspected neoplasm; a diagnostic laparoscopy and the contextual laparotomic removal of abdominal mass; its histological and immunohistochemical analysis. Our main outcome measure is the definition and future recognition of new pathologic entity called malignant epithelioid neoplasm with ACTB-GLI1 fusion. We described for the first time the ultrasound characteristic of this type of lesion using standardized terminology and we believe that it may be the first step to improve the acknowledgement of this novel pathologic entity defined as malignant epithelioid neoplasm with GLI-1 fusions.


Caries arrest using silver diamine fluoride: Knowledge, attitude, and perception of parents in Saudi Arabia.
The objective was to assess the current knowledge, attitudes, and perceptions of parents toward the use of Silver Diamine Fluoride in children's primary teeth and identify related factors. In this cross-sectional study, data were collected from Parents of pediatric patients who had appointments at the King Saud University Pediatric Dentistry Clinic and several private clinics in Riyadh, Saudi Arabia from Jan to April 2021. A simple random sampling method was used. An electronic questionnaire was designed to collect data regarding participants' demographics and their knowledge, attitude, and perception toward the use of SDF for their children. A higher proportion of parents/relatives (87.3%) was strongly satisfied with the speed of treatment and its benefits. In terms of disadvantages, 23.8% and 30.4% of the parents/relatives were satisfied and dissatisfied, respectively (P < 0.05). Regarding attitudes, the majority of participants 22.8% responded as neutral to using SDF to treat their children's anterior primary teeth (P < 0.05), whereas 32.2% agreed to the use of SDF in their children's posterior primary teeth (P < 0.05). A higher proportion of parents/relatives who were in the age group of >50 years (27.8%) had responded as "satisfied" compared with the responses of other age groups (P < 0.05). The present study demonstrates that SDF is acceptable among Saudi parents/relatives to arrest dental caries. However, pigmentation of anterior teeth is a major concern.


Varicella immunity in Iran: an age-stratified systematic review and meta-analysis.
To generate synthesized information on the epidemiology of VZV infection, as well as an estimation of prevalence of age-specific antibody in Iranian less than 40. After exclusion of irrelevant and overlapping reports, 15 papers were included (from nine major cities). Studies were pooled according to the heterogeneity test results. Random effect model methods were used for meta-analysis where significant heterogeneity was observed (age 1-16years).For other age groups, fixed model were used. Significant heterogeneity was observed in prevalence rates of all childhood age-groups. The seropositivity prevalence increased steeply from the age of 1-5 to 6-10 [from 21.9% (95% CI; 10.8-33.1) to 42.1 %(95% CI; 33.6-50.6)]. At the age of 11 15, 59.4% (95% CI; 46.1-72.8) of children showed to be infected. The rate of seropositivity was more than 87% in individuals of 40 and older. The varicella seroeprevalence in Iran is in accordance with average tropical and temperate areas. Comparison of conducted studies during 2003 to 2011 didn't show any alteration in VZV seroprovalence in Iran.


Bell's Palsy-Tertiary Ischemia: An Etiological Factor in Residual Facial Palsy.
The facial nerve is unique among the motor nerves. It has long and tortuous course through the temporal bone and within the Fallopian canal. Because of this it is more prone to paralysis than any other nerve in the body. The most frequent type of facial palsy is Bell's palsy. This is an acute idiopathic lower motor neuron palsy of the facial nerve which does not normally progress and which is most usually unilateral and self limiting,: the majority of cases remit within 4-6 months and nearly always remission is complete by 1 year. In those cases that do not recover it is my contention that this is caused by Either the progression, or after effects, of secondary ischemia: tertiary ischemia. In turn this causes thickening of the facial nerve sheath with a fibrous band or bands forming with resultant strangulation and compression of the nerve, which hampers its recovery. In such cases facial nerve decompression with slitting of the sheath and cutting of any fibrous bands would be the preferred management when allied with aggressive medical therapy.


Medial rather than lateral knee instability correlates with inferior patient satisfaction and knee function after total knee arthroplasty.
It is commonly thought that balanced medial and lateral tibiofemoral joint gaps are essential, but the effect of joint laxity on clinical outcome after total knee arthroplasty (TKA) is unclear. It was hypothesised that medial joint laxity correlates with inferior patient satisfaction and knee function, although lateral joint laxity is allowed to a certain degree in TKA. This study included 50 knees that underwent primary TKA. Knee laxity was measured with postoperative stress radiographs in flexion and extension, and patient satisfaction and knee function were evaluated by the 2011 Knee Society Knee Scoring System. In a comparison of medially tight and medially loose knees in flexion, the scores for satisfaction, symptoms, standard activity, and advanced activity were significantly better in medially tight than in medially loose knees (satisfaction: 29.8, 22.2; symptoms: 20.3, 15.9; standard activities: 24.2, 19.1; and advanced activities: 15.3, 8.7, in the tight and loose knees, respectively). Neither lateral joint laxity during knee flexion nor medial joint laxity during knee extension was associated with a poor postoperative clinical outcome, whereas lateral joint laxity and the standard activity score in extension had a moderate positive correlation. Knees with medial joint laxity during flexion resulted in an inferior postoperative outcome, and lateral joint laxity did not influence patient satisfaction or function. Care should be taken to maintain medial joint stability during the TKA procedure.


Liraglutide therapy beyond glycemic control: an observational study in Indian patients with type 2 diabetes in real world setting.
Liraglutide is an analog of human glucagon-like peptide-1 (GLP-1) and acts as a GLP-1 receptor agonist. Liraglutide is presently used in the treatment of selected patients with type 2 diabetes mellitus (T2DM). To assess efficacy and safety of liraglutide in, overweight and obese Indian patients with T2DM. A single center, prospective, open-labeled, single-arm, observational study for 24 weeks in a real-world setting. Fourteen overweight and obese patients with T2DM who were clinically suitable for liraglutide therapy received liraglutide injections. The starting dose of liraglutide (Victoza) injection was 0.6 mg/day for 3 days followed by 1.2 mg for next 10 days and finally 1.8 mg/day for 22 weeks. Patients were evaluated at baseline and after 12 and 24 weeks of therapy. Adverse events (AE) noted during course of therapy were recorded. A repeated measure analysis of variance was performed to assess statistical significance. Fourteen patients were studied for 24 weeks. After 24 weeks of liraglutide therapy, mean fasting and postprandial plasma glucose decreased by 48.5 mg/dL and 66.71 mg/dL, respectively (P = 0.002 and P = 0004 over 24 weeks, respectively). A mean reduction of 2.26% of glycosylated hemoglobin was noted (P < 0.001 over 24 weeks). Mean decrease in body weight of 8.65 kg and mean decrease in body mass index of 3.26 kg/m(2) was noted (P < 0.001 over 24 weeks for each parameter). Systolic blood pressure was reduced by 15.15 mm of Hg (P = 0.004). Significant improvement in total cholesterol, low-density lipoprotein, triglycerides, and serum creatinine was noted. Nine patients reported AEs. The AEs noticed were nausea (n = 6), feeling of satiety (n = 3), and vomiting (n = 1). No serious AE or hypoglycemic episodes were observed. Liraglutide once a day improved overall glycemic control and was well tolerated. Clinically significant reduction in body weight, systolic blood pressure and improvement in lipid profile were noticed with liraglutide therapy in addition to glycemic control.


Obtaining and characterization of EF-hand mutants of recoverin.
Several EF-hand recoverin mutants were obtained and their abilities to bind to photoreceptor membranes and to inhibit rhodopsin kinase were determined. The mutants with the 'spoiled' 2nd, 3rd or (2nd+3rd) EF-hand structures did not act upon the kinase activity in the microM range of Ca2+ concentrations. Mutations of the 4th EF hand, which 'repaired' its Ca2+-binding activity, resulted in recoverin with three 'working' Ca2+-binding sites. The latter mutant inhibited rhodopsin kinase even more effectively than the wild-type recoverin, containing two working Ca2+-binding structures.


Young investigator challenge: The accuracy of the nuclear-to-cytoplasmic ratio estimation among trained morphologists.
The estimation of the nuclear-to-cytoplasmic ratio (N:C ratio) is an important factor in diagnosing atypia and malignancy in pathological specimens, particularly in cytology. Many algorithms for determining malignant potential make reference to specific, decimal N:C ratios without specifying how the ratio should be measured, with the implication that the observer is intended to estimate this ratio by eye. The authors wanted to determine how accurate trained morphologists (including attending pathologists, pathology residents, and cytotechnologists) are at estimating the N:C ratio without a measuring device. Two surveys were prepared containing ideal and real cell images of various N:C ratios. Participants were instructed to select their best estimate from a list of decimal ratios. The data were tabulated and analyzed to determine how accurate the estimates were and whether there was any performance difference between ideal and real images. The absolute and percentage deviation from the actual N:C ratio decreased steadily with increasing N:C ratio. Aggregate performance was found to be closely correlated between real and ideal images, although interobserver variation was not significantly different among participants in the real images quiz, but was significantly different on the ideal images quiz. Trained morphologists make relatively accurate estimations of the N:C ratio and become increasingly more accurate as the depicted N:C ratio increases. This suggests that including N:C ratio decimals as a criteria for the diagnosis of atypia is valid for high N:C ratios.


In vitro transcription and translation of genomic RNA from a porcine group C rotavirus.
Eleven segments of ssRNA were synthesized from dsRNAs of a porcine group (Gp) C rotavirus (Cowden strain) using an in vitro transcription system. In vitro translation of unfractionated ssRNAs revealed at least nine viral proteins, ranging from 22 kDa to 93 kDa. The 37 kDa and 25 kDa proteins were glycosylated as demonstrated by the endoglycosidase H assay. In vitro translated products analyzed by SDS-polyacrylamide gel electrophoresis and partial protease peptide mapping were comparable to those synthesized in vivo (MA 104 cells).


Family background and physical health of adolescents admitted to an inpatient psychiatric unit, I: Principal caregivers.
A retrospective chart review of 100 consecutive adolescents discharged from a provincial psychiatric hospital adolescent unit was conducted. At the time of admission, eighty-four percent no longer lived with one or both of the biological parents. The children remained with the mother more often than with the father. However, boys who had lost their principal male caregiver more often acquired a new one, compared with girls. The latter tended to remain more in a single-mother home. Thirty-four patients were no longer in the care of either parent at admission. Seventy-four had a conduct disorder. Members of this group were more likely to have lost one or both parents. Recent loss of a parent seemed to be related to a combined diagnosis of depression and conduct disorder. Parental loss was not prominent among one class of the patients with conduct disorder--those with under-socialized aggressive disorders. The latter were often still in their intact biological family of origin, and in four instances they presented serious cases of aggressive actions in the absence of any history of parental deprivation.


Application of the extraction induced by emulsion breaking for the determination of Cu, Fe and Mn in used lubricating oils by flame atomic absorption spectrometry.
A novel approach is proposed for the sample preparation of used lubricating oils to determine Cu, Fe and Mn by FAAS. The method is based on the extraction induced by emulsion breaking, in which the elements of interest are transferred to an aqueous phase before the measurement by FAAS. In the method, each sample of used lubricating oil was diluted with toluene (20% v/v) and the resulting solution was emulsified with a Triton X-114 solution containing HNO3. Further, the water-in-oil emulsion was broken by centrifugation for 30 min at 3500 rpm, originating a system with two well-separated phases: (i) the upper phase, containing the used lubricating oil diluted in toluene and (ii) the lower aqueous phase, containing the analytes that were extracted from oil. The lower phase was collected, diluted with water and the analytes were determined by FAAS. The optimization of the methodology was performed by studying the influence of different parameters that could affect the extraction efficiency such as the nature and concentration of the solvent used for sample dilution, the concentrations of HNO3 and Triton X-114 in the solution employed for emulsification and the operational conditions for extraction (extraction, centrifugation and sampling times). The limits of quantification for Cu, Fe and Mn were 2.9, 77 and 8.2 ng g(-1), respectively. The accuracy of the method was evaluated by comparison with the reference method based on the total digestion of the samples in a closed-vessel microwave oven. There were no statistical differences between the results obtained with the proposed method and the reference one, except for Fe in the cases where its concentration was higher than 80 µg g(-1).


Long-term suppression of insect herbivores increases the production and growth of Solidago altissima rhizomes.
Although insect herbivores have many well documented effects on plant performance, there are few studies that assess the impact of above-ground herbivory on below-ground plant growth. For a seven year period in which no large-scale herbivore outbreaks occurred, a broad spectrum insecticide was utilized to suppress herbivorous insects in a natural community dominated by Solidago altissima. Ramet heights, rhizome lengths, rhizome biomass, and the number of daughter rhizomes all were lower in the control plots than in the insecticidetreated plots. These effects should lead to a decrease in the fitness of genets in the control plots relative to the fitness of genets in the insecticide-treated plots. We also found that ramets in the control plots appear to have compensated for herbivory: the ratio of rhizome length to rhizome biomass was greatest in the control plots, which indicates that clones moved farther per unit biomass in these plots than in the insecticide-treated plots. Clonal growth models show that this shift in allocation patterns greatly reduced the magnitude of treatment differences in long-term clonal displacements.Previous work has shown, and this study verified, that clonal growth in S. altissima is well represented by random-walk and diffusion models. Therefore, we used these models to examine possible treatment differences in rates of clonal expansion. Although rhizome lengths were greater in the insecticide-treated plots, results from the models suggest that our treatments had little impact on the short- and long-term displacement of S. altissima ramets from a point of origin. This occurred because S. altissima ramets backtrack often, and thus, treatment differences in net displacements are less pronounced than treatment differences in rhizome lengths.


Glycerogenic pathway in the rat mammary gland.
The conversions of the isotope from [1-14C]acetate, [1-14C]glucose and [6-14C]glucose to CO2 and fatty acids in acini isolated from the mammary gland at the peak of lactation were studied. The incorporation of [9,10-3H]oleate into triacylglycerol synthesis as single substrate or in combination with substrates that potentially may supply trioses-phosphate was also determined. The rate of fatty acid synthesis paralleled the activity of the hexose monophosphate shunt and the data obtained reveal that little carbon from triose stage enters the phosphohexose pool via reversal of glycolytic pathway. The results are interpreted in terms of the NADPH producing systems and phosphoenolpyruvate carboxykinase activities as well as the possible implications in lipogenic and glyceroneogenic pathways.


Commentary on "Cervical cancer screening in England: the past, present, and future": a comparison with Canada.
For cervical cancer screening to be most effective, all eligible women in the population must be enrolled in an organized program. In this issue, Albrow et al describe how cervical cancer screening in England migrated from "opportunistic" in the 1960s to "organized" in the 1980s and discuss its continued evolution as new screening approaches and technologies developed. England's current National Health Services Cervical Screening Programme is the poster child for organized screening delivery. A similar model of central coordination and peripheral delivery of screening does not exist in Canada. The provision of health services is under provincial jurisdiction, and consequently each province administers its own version of a cervical cancer screening program. To date, organized screening has only been achieved in 2 of 10 provinces, and screening elsewhere is opportunistic. Screening in Canada begins at age 18-21, ends at age 69-70, and mostly occurs annually. This approach has yielded a significant reduction in cervical cancer incidence and mortality, but health service utilization costs have been high. The future should see full implementation of organized screening in all provinces, and when combined with the publicly funded human papillomavirus vaccination program of young girls begun in 2008, the result should be even better cancer control. Cancer (Cancer Cytopathol) 2012;. © 2011 American Cancer Society.


Optimized combined low level light therapy and intense pulsed light therapy for the treatment of dry eye syndrome caused by Meibomian glands dysfunction.
Dry eye syndrome (DES) is a common disease that can lead to ocular discomfort, reduced visual acuity and reduced quality of life. Meibomian Gland dysfunction plays an important role in most cases. To evaluate the effects of "EyeLight", a novel device delivering combined intense pulsed light (IPL) and low-level light therapy (LLLT), we conducted a retrospective chart review of patients refractory to conventional medical treatment who were treated with "EyeLight" therapy at Laser Vision, Lebanon. Each patient received between 2 to 5 treatment sessions. Clinical measurements were obtained before and after each session, including tear film breakup time (TBUT), ME-CHECK-meiboscale and the ME-CHECK questionnaire to determine the need for an additional session and to monitor progress. The same clinical evaluation was performed 3 to 5 weeks after the final treatment. A total of 52 eyes were included. A significant improvement in objective clinical signs was found, with an increase in TBUT from 6.98±1.41s. to 9.27±1.25s. (P<0.001) and a decrease in ME-CHECK-meiboscale (P<0.001). A reduction of severity level on the ME-CHECK-meiboscale classification was observed in 90%, along with a significant improvement in subjective clinical signs on the ME-CHECK questionnaire (P<0.001). No ocular or facial adverse events were noted. "EyeLight" treatment of 2 to 5 sessions depending on the severity of MGD in each eye showed an improvement in objective clinical signs and subjective symptoms and therefore appears to be an effective treatment for DES related to MGD refractory to conventional treatment.


Calculation of probabilities of random occurrence of different types of palindromes.
Formulas for the calculation of probabilities of the random occurrence of different types of true and complementary palindromes in DNA of arbitrary nucleotide composition were proposed. Calculations using the formulas developed show that the probabilities of random occurrence depend significantly, as expected, on the combinatorial restrictions, imposed on the palindromes, and in some cases also on the nucleotide composition of the DNA. Calculations performed demonstrated that even comparatively short (6/8 etc.) palindromes of certain types could ensure the required specificity of the protein-DNA interaction in transcription, replication etc.


Imaging of hepatic hemangioma: from A to Z.
The hemangioma is the most common solid lesion of the liver. Therefore, radiologists must know the typical and atypical imaging findings of this lesion in order to reach a correct diagnosis and avoid diagnostic errors. However, only few papers have comprehensively described the entire spectrum of atypical and uncommon imaging features. In this updated review, we provide the imaging features of hepatic hemangioma, in both typical and atypical forms, as well as its association with abnormalities in the adjacent hepatic parenchyma and other hepatic lesions, and its complications.


Attenuation of neuroinflammation reverses Adriamycin-induced cognitive impairments.
Numerous clinical studies have established the debilitating neurocognitive side effects of chemotherapy in the treatment of breast cancer, often referred as chemobrain. We hypothesize that cognitive impairments are associated with elevated microglial inflammation in the brain. Thus, either elimination of microglia or restoration of microglial function could ameliorate cognitive dysfunction. Using a rodent model of chronic Adriamycin (ADR) treatment, a commonly used breast cancer chemotherapy, we evaluated two strategies to ameliorate chemobrain: 1) microglia depletion using the colony stimulating factor-1 receptor (CSF1R) inhibitor PLX5622 and 2) human induced pluripotent stem cell-derived microglia (iMG)-derived extracellular vesicle (EV) treatment. In strategy 1 mice received ADR once weekly for 4 weeks and were then administered CSF1R inhibitor (PLX5622) starting 72 h post-ADR treatment. ADR-treated animals given a normal diet exhibited significant behavioral deficits and increased microglial activation 4-6 weeks later. PLX5622-treated mice exhibited no ADR-related cognitive deficits and near complete depletion of IBA-1 and CD68+ microglia in the brain. Cytokine and RNA sequencing analysis for inflammation pathways validated these findings. In strategy 2, 1 week after the last ADR treatment, mice received retro-orbital vein injections of iMG-EV (once weekly for 4 weeks) and 1 week later, mice underwent behavior testing. ADR-treated mice receiving EV showed nearly complete restoration of cognitive function and significant reductions in microglial activation as compared to untreated ADR mice. Our data demonstrate that ADR treatment elevates CNS inflammation that is linked to cognitive dysfunction and that attenuation of neuroinflammation reverses the adverse neurocognitive effects of chemotherapy.


A single-center cytogenetic study of 629 Chinese patients with de novo acute myeloid leukemia--evidence of major ethnic differences and a high prevalence of acute promyelocytic leukemia in Chinese patients.
Cytogenetic information is important in the diagnosis, classification, and prognostication of acute myeloid leukemia (AML). Data obtained from multicenter treatment trials are well published. In this study, we contribute cytogenetic data from a large series of 629 Chinese patients with de novo AML that were karyotyped in a single laboratory. A higher prevalence of acute promyelocytic leukemia was observed when compared with non-Chinese series. The difference was most prominent in the younger age group. Abnormalities at chromosomal region 11q23 and inv(16) seemed uncommon. These ethnic differences may indicate underlying genetic susceptibility to AML development and/or environmental differences. More comprehensive data on AML in the elder population are needed to assess the role of cytogenetics in predicting prognosis and guiding treatment in this large subgroup of patients.


[The effects of suicide gene therapy system on adenoid cystic carcinoma of salivary gland in athymic mice].
To study the effects of HSV-tk/GCV system on adenoid cystic carcinoma (ACC) in vivo. The cell strain of ACC-M (highly metastatic to the lung) was inoculated into the flank of nude mice, then treated with HSV-tk/GCV system. The system can inhibit the tumor growth greatly, moreover this function has bystander effect. HSV-tk/GCV system can be to treat ACC.


[Swallowing sound signal: description in normal and laryngectomized subjects].
Recently, we described three sound components in the pharyngeal swallowing sound. The aim of the present study was to identify the origin of these components using modern techniques providing numeric, synchronized acoustic-radiological data in a normal population and in a partial supracricoid laryngectomized population (SCL group) and a total laryngectomized (TL group) population in pre- and postoperative situations. We enrolled 15 normal subjects (10 men and five women; mean age, 29.5+/-8 years), 11 patients in the SCL group (11 men; mean age, 62; range, 45-75 years), and nine patients in the TL group (three women, six men; mean age, 56; range, 39-73). An X-ray camera was connected to a video acquisition card to obtain acoustic-radiological data (2 images/s). The microphone was attached to each subject's skin overlying the lateral border of the cricoid. The subjects were asked to swallow 10 ml of a barium suspension. We performed the acoustic-radiological analysis using Visualisation and Cool Edit Pro software. Each sound component was associated with a specific position of the bolus and the moving anatomic structure. Three sound components were identified: the laryngeal ascension sound (LAS), the upper sphincter opening sound (USOS), and the laryngeal release sound (LRS). We quantified the total duration of the pharyngeal sound and its components, as well as the duration of the interval. The average duration of the normal pharyngeal sound was 690+/-162 ms and was significantly decreased in the TL group (296+/-105 ms) and increased in the SCL group (701+/-186 ms). The USOS was present in 100% of the recordings. A typical profile of the swallowing sound for each group was obtained. This study allowed us to determine the origin of the three main sound components of the pharyngeal swallowing sound with respect to movements in anatomic structures and the different positions of the bolus, and to describe the main variations induced by a partial and a total laryngectomy.


Gene transfection of primary mouse hepatocytes in 384-well plates.
We report the development of an improved in vitro transfection assay to test the efficiency of non-viral vector DNA nanoparticle transfection of primary hepatocytes. The protocol describes the isolation of viable hepatocytes from a mouse by collagenous perfusion. Primary mouse hepatocytes are plated in 384-well plates and cultured for 24 h prior to transfection with polyethylenimine (PEI) or peptide DNA nanoparticles. Luciferase expression is measured after 24 h following the addition of ONE-Glo substrate. The gene transfer assay for primary hepatocytes was optimized for cell plating number, DNA dose, and PEI to DNA ratio. The assay was applied to compare the expression mediated by mRNA relative to two plasmids possessing different promoters. The reported assay provides reliable in vitro expression results that allow direct comparison of the efficiency of different non-viral gene delivery vectors.


[Influence of Teamwork on Wellbeing And Emotional Exhaustion of Staff in German Rehabilitation Clinics].
In the context of high prevalence rates of mental and psychosomatic disorders in the medical staff, emotional exhaustion and wellbeing are often considered as important indicators. Teamwork can have a positive influence on wellbeing of staff members. In the sector of rehabilitation, however, this is not sufficiently investigated. The aim of this study was to investigate aspects of teamwork as predictors of wellbeing and emotional exhaustion in staff at rehabilitation clinics in Germany. Data was collected in 10 rehabilitation clinics, 9 of them could be included in the data analysis (n=306, 70% female, 68% age 40-59). Data was analyzed with multiple linear regression analyses. Staff reported moderate rates of emotional exhaustion and good rates of overall wellbeing. Results of the regression analysis show that cohesion (β=0.27, p<0,001), team organization (β=0.19, p<0,01) and age (β=0.13, p<0,05) could predict wellbeing (F[3, 244]=19.38, p<0,05). Emotional exhaustion was predicted by cohesion (β=- 0.37, p<0,001, F[1, 244]=39.19). Consequences of interpersonal andstructural aspects of teamwork are discussed as well as the potential relevance of interventions to improve teamwork, in order to enhance wellbeing and counteract emotional exhaustion of staff members.


Development of a model for a structured support group for patients following bariatric surgery.
Bariatric surgery is performed to alleviate the major health problems associated with morbid obesity. However, after surgery, patients must learn to deal with new self-images and old behavior patterns that may precipitate a return to the pre-surgery status. Thus, long-term follow-up and continued emotional support are essential ingredients for a successful bariatric surgery outcome. Patients who attend group meetings regularly, tend to lose more weight. Patients are encouraged to participate in a structured support group both before and after bariatric surgery. The current model of the group incorporates self-responsibility, aspects of the "relapse prevention" model, and group therapy processes. Additionally the group is flexible, to adapt to the needs of the evolving group membership.


A fluorescent sterol probe study of human serum low-density lipoproteins.
The fluorescent sterol probe, ergosta-5,7,9,(11),22-tetraen-3 beta-ol (dehydroergosterol), was utilized as a cholesterol analog to label human serum low-density lipoproteins (LDL). Quenching of dehydroergosterol fluorescence by KI indicated that most of the fluorophore was either buried within the outer phospholipid monolayer of LDL or within the neutral lipid core of LDL. The steady-state anisotropy of dehydroergosterol in LDL detected the cholesteric core phase transition near 30 degrees C. Fluorescence lifetime decays for dehydroergosterol contained two components, both below and above the cholesteric phase transition, with the major lifetime component near 1 ns. Neither lifetime component underwent a detectable change in duration at the core phase transition temperature. Time-correlated fluorescence anisotropy decays of dehydroergosterol indicated a single rotational correlation time near 1.7 ns, which was unaffected by the core phase transition. Time-correlated anisotropy decays also suggested hindered rotation of dehydroergosterol in LDL. These results indicate that unesterified cholesterol is primarily located in the outer phospholipid monolayer of LDL, with the majority of cholesterol not in direct contact with the aqueous phase.


Kinetics of implant-induced inflammatory angiogenesis in abdominal muscle wall in mice.
Injury of skeletal abdominal muscle wall is a common medical condition and implantation of synthetic or biological material is a procedure to repair musculofascial defects. We proposed to characterize the dynamics of inflammatory cell recruitment, newly formed blood vessels, cytokine production and fibrogenesis in the abdominal skeletal muscle in response to polyether-polyurethane sponge implants in mice. At 2, 4, 7 and 10days after implantation the muscle tissue underneath the sponge matrix was removed for the assessment of the angiogenic response (hemoglobin content, vascular endothelial growth factor and morphometric analysis of the number of vessels) and inflammation (myeloperoxidase and n-acethyl-B-d-glucosaminidase activities, cytokines). In addition, muscle fibrogenesis was determined by the levels of TGF-β1 and collagen deposition. Hemoglobin content, wash out rate of sodium fluorescein (indicative of blood flow) and the number of vessels increased in the abdominal muscle bearing the synthetic matrix in comparison with the intact muscle. Neutrophil recruitment peaked in the muscle at day 2, followed by macrophage accumulation at day 4 post-injury. The levels of the cytokines, VEGF, TNF-α, CCL-2/MCP-1 were higher in the injured muscle compared with the intact muscle and peaked soon after muscle injury (days 2 to 4). Collagen levels were higher in sponge-bearing muscle compared with the non-bearing tissue soon after injury (day 2). The implantation technique together with the inflammatory and vascular parameters used in this study revealed inflammatory, angiogenic and fibrogenic events and mechanisms associated with skeletal muscle responses to synthetic implanted materials.


A novel mutation in ornithine transcarbamylase gene causing mild intermittent hyperammonemia.
We report a 3-year-old Saudi boy with recurrent episodes of vomiting, poor feeding, and altered mental status accompanied by an intermittent mild hyperammonemia, and a large elevation of urinary orotic acid. Sanger sequencing of the ornithine transcarbamylase (OTC) gene revealed a novel hemizygous deletion at the fourth nucleotide of intron 4 (c.386+4delT) in the proband and his asymptomatic mother. This novel mutation in the OTC gene is responsible for the late-onset phenotype of OTC deficiency.


Type 2 diabetes-associated fatty acid binding protein 2 promoter haplotypes are differentially regulated by GATA factors.
The human intestinal fatty acid binding protein 2 (FABP2) mediates fat absorption by binding and intracellular trafficking of long-chain free fatty acids. Studies with knockout mice and association analysis of polymorphisms revealed that FABP2 is a susceptibility gene for type 2 diabetes (noninsulin dependent diabetes mellitus [NIDDM]) and related traits. Relevant FABP2 promoter polymorphisms c.-80_-79insT (rs5861422), c.-136_-132delAGTAG (rs5861423), c.-168_-166delAAGinsT (rs1973598), c.-260G>A (rs6857641), c.-471G>A (rs2282688), and c.-778G>T (rs10034579) result in two haplotypes A and B, whereby B possesses two- to three-fold lower transcriptional activity than A. We show in luciferase reporter gene assays by a series of chimeric FABP2 promoter constructs in intestinal Caco-2 cells that polymorphism c.-80_-79insT essentially determines different activities of the FABP2 promoter. In accordance, in electrophoretic mobility shift assays (EMSAs), transcriptional factors GATA-5 and -6 bind with higher binding affinities to the FABP2 promoter region containing the -80A allele compared to B. As functional consequence, haplotype A is twice as much more activated by GATA factors than haplotype B in liver Huh7 cells. Additionally, a construct bearing the -80B allele in the background of haplotype A reversed the activity from A to B. Thus, the GATA mediated differential activation of FABP2 haplotypes depends on polymorphism c.-80_-79insT. This provides the molecular basis for the variant specific transcriptional regulation of the diabetes type 2-associated FABP2 gene.


Assembly of propylene glycol alginate/β-lactoglobulin composite hydrogels induced by ethanol for co-delivery of probiotics and curcumin.
Probiotics and curcumin can exhibit synergistic biological activities on the basis of a gut-brain axis, but are sensitive to environmental conditions, making it a challenge for their co-utilization. To meet the demand for high efficiency and convenience, both probiotics and curcumin were encapsulated within a propylene glycol alginate-based hydrogel delivery system, which was assembled using an ethanol-induced approach. The composite hydrogel was effective at sustaining the release of curcumin and protecting LGG cells in simulated gastrointestinal tract conditions. Moreover, it could also largely reduce the chemical degradation of curcumin and increase the survival of LGG during light exposure and long-term storage: up to 91.3 % of curcumin and 9.72 log CFU cm-3 remained present throughout 4 weeks of storage. Results in this work demonstrate a low-energy and green approach to assemble a composite hydrogel with remarkable biocompatibility, which is considered as a desired delivery vehicle for co-delivery of probiotics and curcumin.


Kannada Translation and Validation of the ESAS-r Renal for Symptom Burden Survey in Patients with End-Stage Kidney Disease.
End-stage kidney disease (ESKD) is a life-limiting illness that leads to significant health-related suffering for the patients and their caregivers. Moreover, disease-directed options such as dialysis and renal transplant might not be universally accessible. Inadequate assessment and management of symptoms often lead to diminished quality of life. For evaluating symptoms and their associated distress, various tools have been identified. However, these are not available for the native Kannada-speaking population for assessing ESKD symptom burden. In this study, we determined the reliability and validity of the Edmonton Symptom Assessment System Revised Renal (ESAS-r: Renal) in Kannada-speaking ESKD patients. ESAS-r: Renal English version was translated into Kannada using the forward and backward method. The translated version was endorsed by Nephrology, Palliative care, Dialysis technology and Nursing experts. As a pilot study, 12 ESKD patients evaluated the content of the questionnaires for appropriateness and relevance. The ESAS-r: Renal Kannada version was validated by administering this tool to 45 patients twice a fortnight. The translated ESAS-r: Renal Kannada version questionnaire had an acceptable face and content validity. Experts' opinion was assessed by content validity ratio (CVR), and the value of CVR of ESAS-r: Renal Kannada version was-'1'-. Internal consistency of the tool was assessed among Kannada-speaking ESKD patients; its Cronbach's α was 0.785, and test-retest validity was 0.896. The validated Kannada version of ESAS-r: Renal was reliable and valid for assessing symptom burden in ESKD patients.


Probing autoxidation of oleic acid at air-water interface: A neglected and significant pathway for secondary organic aerosols formation.
Fatty acids have been proposed to be a potential source of precursors for SOAs, but the autoxidation process was neglected in the oxidation studies. Here, the autoxidation of oleic acid was explored using microdroplet mass spectrometry. Bulk solution, concentration and solvent composition experiments provided direct evidences for that the autoxidation occurred at or near the air-water interface. The kinetic data showed an acceleration at this interface and was comparable to ozonation, indicating that autoxidation is an important pathway for SOAs formation. In addition, intermediates/products were captured and identified using tandem mass spectrometry, spin-trapping and quenched agents. The autoxidation mechanism was divided into addition intermediates (AIs) and Criegee intermediates (CIs) pathways mediated by hydroxyl radicals (OH). The CI chemistry which is ubiquitous in gas phase was observed at the air-water interface, and this leaded to the mass/volume loss of aerosols. Inversely, the AI chemistry caused the increase of mass, density and hygroscopicity of aerosols. AI chemistry was dominated compared to CI chemistry, but varied by concerning aerosol sizes, ultraviolet light (UV) and charge. Moreover, the MS approach of selectively probing the interfacial substances at the scale of sub-seconds opens new opportunities to study heterogeneous chemistry in atmosphere.


What students with intellectual disabilities know about writing planning.
Studies on the writing of students with intellectual disabilities have been scarce and unrepresentative. Therefore, the purpose of this research was to analyse this group of students' abilities to plan their texts METHOD: A collective case study was carried out, with an eminently qualitative approach, although aided by an initial quantitative analysis. Fifteen students with unspecified intellectual disabilities were interviewed using open-ended questions. For data interpretation, content analysis and quantification of responses were used. The results revealed the abilities and limitations of these students regarding the knowledge and use of one of the key processes of written expression (writing planning). The cognitive operations of planning, in which these students admitted the greatest problems, were the ordering and recording of ideas, and textual structuring.


Child and parent perceptions of children's psychopathology in psychiatric outpatient children.
This study investigated the clinical utility of multitrait-multimethod assessments of internalizing and externalizing symptoms in child psychiatric outpatients. Mothers tended to rate all symptoms of psychopathology at higher levels of severity than their children. In contrast to studies of inpatients, much stronger convergent validity of child and mother ratings was obtained. Overall, findings yielded little evidence of discriminant validity, although mothers appeared better able to discriminate between internal and external symptomatology than their children. Methodological and theoretical explanations of these findings are discussed.


Branchio-oto-renal syndrome: comprehensive review based on nationwide surveillance in Japan.
Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized by branchiogenic malformation, hearing loss and renal anomalies. The prevalence of BOR syndrome is 1/40,000 in Western countries, and nationwide surveillance in 2009-2010 identified approximately 250 BOR patients in Japan. Three causative genes for BOR syndrome have been reported thus far: EYA1, SIX1, and SIX5, but the causative genes for approximately half of all BOR patients remain unknown. This review article discusses the epidemiology, clinical symptoms, genetic background and management of BOR syndrome.


Microbiological diagnosis of spinal tuberculosis.
The purpose of this study was to review the clinical features and diagnosis of spinal tuberculosis cases reported in the literature. A medical literature search in the Medline Pubmed database was undertaken to review tuberculosis spinal infection and extra-pulmonary tuberculosis diagnosis improvement. We introduced the following search items and boolean operators: "spinal infection", "spinal tuberculosis infection", "microbiological diagnosis of spinal tuberculosis" and "spinal tuberculosis PCR." Single cases or series without microbiological diagnosis were rejected. Manuscript language was restricted to Spanish, French, and English versions. Spinal tuberculosis is more common in developing countries and is probably underdiagnosed. Delayed diagnosis is characteristic; it worsens the prognosis and increases morbidity. The microbiological diagnosis is crucial for several reasons. Despite surgical treatment, medical treatment with anti-tuberculous drugs is always necessary. A total of 20-40% of the spinal tuberculosis patients show another locus of infection. Pulmonary location can become a public health problem. Previously treated patients for other tuberculosis locations, incomplete treatments, or poor adherence can change the M. tuberculosis sensitivity pattern. Drug resistance test becomes a major need in the microbiology laboratory. PCR diagnostic techniques advance the diagnosis and increase the sensitivity and specificity rate.


[Purification from a total cellular lysate of a protein modifying the sensitivity of Na+/K+ ATPase to ouabain].
A protein (32,000 dalton) has been purified from M2FS cells derived from the murine plasmocytoma MOPC 173. Like tropomyosin, this protein when added with Ca++ to EDTA-treated plasma membranes prepared from the same cell, induced a drastic increase in the Na+/K+ atpase resistance to ouabain.


Antipyrine and metronidazole metabolism during occupational exposure to gasoline.
Antipyrine and metronidazole clearance was measured in 18 fuel-filling attendants by the single-sample method while the attendants were being exposed occupationally to gasoline; the measurements were repeated after 2-4 weeks with no exposure. Eighteen office workers were investigated simultaneously. The median concentration of gasoline in the breathing zone of the fuel-filling attendants during filling and cleaning operations was 270 mgm-3 (range 18-1758 mgm-3). Antipyrine clearance was 18% higher during exposure to gasoline than after 2-4 weeks of vacation (P less than 0.01), while antipyrine clearance was unchanged in the office workers. No change was found in metronidazole clearance in either group. Antipyrine clearance was on average 26% higher in the smokers than in the nonsmokers (P less than 0.05), while metronidazole clearance was similar in smokers and nonsmokers. We conclude that gasoline is an inducer of antipyrine elimination, with no impact on metronidazole elimination. This indicates that gasoline has a differential inducing effect on the hepatic drug metabolizing enzymes of man.


Differences in the distribution of urea and creatinine between red cells and plasma in normal and azotemic blood as assessed by autoanalyzer and manual chemical methods.
It has been proposed that urea and creatinine may bind to red cell constituents. In the present studies, whole blood and plasma concentrations of urea and creatinine were compared using autoanalyzer techniques (that require solutes to pass through a dialysis membrane) and manual techniques (with no dialysis membrane). Blood samples from 11 normal and 10 azotemic subjects were studied. Concentration differences between plasma water and red cell water for these solutes were significant in normals with standard manual but not with autoanalyzer methods. Accordingly, red cell water concentrations in normals were greater with manual methods than with autoanalyzer methods. In azotemics, differences between red cell and plasma water concentrations and differences in red cell water concentrations between methods were proportionately less. The findings suggest that accumulation of these solutes in the red cell in azotemia is predominantly in the freely diffusable form. Any chemical interference of red cell proteins and/or solute binding to red cell constituents yields significant discrepancies between manual and autoanalyzer methods only at lower BUN and creatinine concentrations.


Regulation of astrocyte pathology by fluoxetine prevents the deterioration of Alzheimer phenotypes in an APP/PS1 mouse model.
Studies have implicated astrocytic dysfunction in Alzheimer's disease (AD). However, the role of astrocytes in the pathophysiology and treatment of the disease is poorly characterized. Here, we identified astrocytes as independent key factors involved in several Alzheimer-like phenotypes in an APP/PS1 mouse model, including amyloid pathology, altered neuronal and synaptic properties, and impaired cognition. In vitro astrocytes from APP/PS1 mice induced synaptotoxicity as well as reduced dendritic complexity and axonal branching of hippocampal neurons. These astrocytes produced high levels of soluble β-amyloid (Aβ) which could be significantly inhibited by fluoxetine (FLX) via activating serotonin 5-HT2 receptors. FLX could also protect hippocampal neurons against astrocyte-induced neuronal damage in vitro. In the same APP/PS1 mice, FLX inhibited activation of astrocytes, lowered Aβ products, ameliorated neurotoxicity, and improved behavioral performance. These findings may provide a basis for the clinical application of FLX in patients, and may also lay the groundwork for exploration of other novel astrocyte-based therapies of AD.


SPARCL1 impedes trophoblast migration and invasion by down-regulating ERK phosphorylation and AP-1 production and altering EMT-related molecule expression.
Embryo implantation depends on trophoblast cells migration and invasion. Abnormal function of trophoblast cells could result in many pregnancy complications. Secreted protein acidic and rich in cysteine like-1 (SPARCL1) has been reported to inhibit cell migration and tumor invasion. This study aimed to explore the role of SPARCL1 in trophoblast functions. Villous specimens were obtained from 31 women with spontaneous abortion and 31 women with normal early pregnancy to determine the expression of SPARCL1. HTR8/SVneo cells and JAR cells were transfected with pIRES2-EGFP-SPARCL1 vectors and control vectors. The proliferation assay and scratch-wound assay were performed. Quantitative polymerase chain reaction (qPCR) and western blotting were performed to assess epithelial mesenchymal transition (EMT)-related molecules including MMP2, MMP3, N-cadherin, E-cadherin and vimentin. Extracellular signal-regulated kinase (ERK) phosphorylation activity and AP-1 expression in HTR8/SVneo cells following multi-scratching were detected using above assays. The mRNA and protein levels of SPARCL1 were significantly higher in the abortion group than in the normal pregnancy group. After transfection, there was no difference of cell viability between the SPARCL1-overexpression group and control vector group. However, the migration distance and area were reduced and the abundances of EMT related molecules were changed by SPARCL1 overexpression when compared with controls. Lower ERK phosphorylation activity and decreased Fos and Jun expressions were noted at high level of SPARCL1. Restrained migration and invasion were noted in trophoblast cells with SPARCL1 overexpression, which might affect embryo implantation and placenta development. It could be involved in the pathogenesis of spontaneous abortion.


Local administration of platelet-derived growth factor B (PDGFB) improves follicular development and ovarian angiogenesis in a rat model of Polycystic Ovary Syndrome.
Alterations in ovarian angiogenesis are common features in Polycystic Ovary Syndrome (PCOS) patients; the most studied of these alterations is the increase in vascular endothelial growth factor (VEGF) production by ovarian cells. Platelet-derived growth factor B (PDGFB) and D (PDGFD) are decreased in follicular fluid of PCOS patients and in the ovaries of a rat model of PCOS. In the present study, we aimed to analyze the effects of local administration of PDGFB on ovarian angiogenesis, follicular development and ovulation in a DHEA-induced PCOS rat model. Ovarian PDGFB administration to PCOS rats partially restored follicular development, decreased the percentage of cysts, increased the percentage of corpora lutea, and decreased the production of anti-Müllerian hormone. In addition, PDGFB administration improved ovarian angiogenesis by reversing the increase in periendothelial cell area and restoring VEGF levels. Our results shed light into the mechanisms that lead to altered ovarian function in PCOS and provide new data for potential therapeutic strategies.


Surface-engineered nanostructured lipid carrier systems for synergistic combination oncotherapy of non-small cell lung cancer.
Nanoparticle-aided combination chemotherapy offers several advantages like ratiometric drug delivery, dose reduction, multi-targeted therapy, synergism, and overcoming multi-drug resistance. The current research was instigated to facilitate targeted and ratiometric co-delivery of docetaxel (DT) and curcumin (CR) through the development of folate (FA)-appended nanostructured lipid carriers (NLCs), i.e., FA-DTCR-NLCs to lung cancer cells. The FA-DTCR-NLCs were formulated by employing a scaleable and solvent-free high-pressure homogenization approach. The FA-DTCR-NLCs were evaluated for in vitro and in vivo characteristics using suitable analytical and statistical techniques. The FA-DTCR-NLCs demonstrated physicochemical properties and particokinetics suitable for targeted, ratiometric co-delivery of the anticancer agents. This was further affirmed by significantly better in vivo relative bioavailability of DT (24.85 fold) with FA-DTCR-NLCs as compared with Taxotere® (p < 0.05) and cell line studies. A significant tumor regression was observed from the results of tumor staging in a murine model of lung carcinoma (p < 0.05). Immunostaining of the tumor sections with tumor differentiation biomarkers suggested considerably higher apoptotic, anti-proliferative, anti-angiogenic, and anti-metastatic potential of FA-DTCR-NLCs compared with Taxotere®. In vivo toxicity assessment of the FA-DTCR-NLCs demonstrated a noteworthy reduction in DT associated side effects. The in vitro and in vivo pre-clinical findings prove the therapeutic and safety pre-eminence of FA-DTCR-NLCs for the treatment of NSCLC.


The effect of cryopreservation on the capacitation status and epithelial cell attachment capability of dog spermatozoa.
Freezing and cooling of spermatozoa during cryopreservation for artificial insemination causes ultrastructural changes in the acrosome and plasma membrane which reduces longevity and fertility. Cryopreservation-induced capacitation-like changes and reduced ability of spermatozoa to bind to the cells of the reproductive tract of the bitch may contribute to the reduced fertility of cryopreserved spermatozoa. Previous studies in the dog have investigated the effects of extending and cooling spermatozoa on the plasma membrane but often only after freeze-thawing and not in conjunction with an assessment of their ability to bind to uterine tube epithelial explants. This study investigated the effect of each stage of the cryopreservation process on capacitation and attachment to the reproductive tract of the bitch. The capacitation status of spermatozoa was studied over time after cryopreservation using a chlortetracycline and Hoechst 33258 stain. The ability of spermatozoa to bind to uterine tube epithelial explants was studied using Hoechst 33342 stain. Extending, cooling and freeze-thawing promoted capacitation and decreased the spermatozoal binding ability. The effect of each stage appeared to be cumulative with the freeze-thawing stage being the most dramatic. The results suggested that the cumulative effect of each stage of the cryopreservation process results in the promotion of capacitation before spermatozoa have reached the site of fertilisation, and therefore spermatozoa have reduced ability to attach to epithelial cells. These effects are contributory factors to the reduced fertility of cryopreserved spermatozoa.


Antagonistic activity of 24-oxa-analogs of vitamin D.
24-Oxa-vitamin D3 (24-oxa-D3) and 24-oxa-1 alpha-hydroxyvitamin D3 were designed as possible inhibitors of the vitamin D metabolic activation pathway. Their affinity for the vitamin D receptor (from pig intestine) and human vitamin binding protein were reduced, and their potency to induce cell differentiation of human leukemia cells (HL 60) or osteosarcoma cells (MG 63) was markedly reduced (19% and 3%, respectively), in comparison with calcitriol. A single or chronic injection of 24-oxa-D3 had no biological activity, whereas chronic administration of 24-oxa-1 alpha-hydroxy-D3 showed weak agonist activity in rachitic chicks. When the 24-oxa-D3 was given prior to a single injection of vitamin D3, lower values of serum calcium (64% of the value obtained in vitamin D-treated animals), osteocalcin (52%), 25-(OH)D3 (45%) and duodenal calbindin-D 28K (9.4%) were found. When given chronically in a 100-fold more excess no clear antagonistic effects were observed. 24-Oxa-D3 is thus a new metabolic weak antagonist of vitamin D3, but adding a hydroxyl group at C-1 creates a weak agonist.


First record of partial albinism in the critically endangered Angelshark (Squatina squatina) (Linnaeus, 1758).
We report the first case of partial albinism in the Critically Endangered angelshark, Squatina squatina. The encounter with this specimen took place while SCUBA diving on the beach of Tufia, located on the east coast of the island of Gran Canaria on 2 April 2021. This is also the first confirmed finding of an albino elasmobranch specimen in the Canary Island archipelago.


Epidemiology of Group A rotavirus in rodents and shrews in Bangladesh.
Rodents and shrews live in close proximity to humans and have been identified as important hosts of zoonotic pathogens. This study aimed to detect Group A rotavirus (RVA) and its potential risk factors in rodents and shrews in Bangladesh. We captured 417 small mammals from 10 districts with a high degree of contact between people and domestic animals and collected rectal swab samples between June 2011 and October 2013. We tested the swab samples for RVA RNA, targeting the NSP3 gene segment using real-time reverse transcription-polymerase chain reaction (rRT-PCR). Overall, RVA prevalence was the same (6.7%) in both rodents and shrews. We detected RVA RNA in 5.3% of Bandicota bengalensis (4/76; 95% CI: 1.4-12.9), 5.1% of B. indica (4/79; 95% CI: 1.4-12.4), 18.2% of Mus musculus (4/22; 95% CI: 5.2-40.3), 6.7% of Rattus rattus (6/90; 95% CI: 2.5-13.9), and 6.7% of Suncus murinus (10/150; 95% CI: 3.2-11.9). We found significantly more RVA in males (10.4%; OR: 3.4; P = 0.007), animals with a poor body condition score (13.9%; OR: 2.7; P = 0.05), during wet season (8.3%; OR: 4.1; P = 0.032), and in urban land gradients (10.04%; OR: 2.9; P = 0.056). These findings form a basis for understanding the prevalence of rotaviruses circulating among rodents and shrews in this region. We recommend additional molecular studies to ascertain the genotype and zoonotic potential of RVA circulating in rodents and shrews in Bangladesh.


The Lack of Standardized Outcomes for Surgical Salvage of HPV-Positive Recurrent Oropharyngeal Squamous Cell Carcinoma: A Systematic Scoping Review.
Although HPV status is known to provide an improved prognosis in initial treatments of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), it is unclear how it affects patients who receive salvage surgery (SS), which has historically poor survival rates. The purpose of this study was to evaluate the role of SS for patients with locoregional recurrence (LRR) of HPV-positive OPSCC and its impact survival rates. We conducted a scoping review of literature through October 2022 and included 995 individuals. Survival endpoints, such as overall survival (OS), Kaplan-Meier curves, and median post-recurrence survival, were analyzed in addition to demographics. Of all studies, 18.8% (6/32) reported any survival data for SS patients, with the most prevalent reporting 2- and 5-year OS in two studies. Median post-recurrence survival was not reported for SS. These findings reveal the limited and unpredictable reporting of survival-specific data on SS for HPV-positive OPSCC. With limited survival assessment, it is difficult to assess the potential advantages and disadvantages of this therapy to guide clinical decision-making.


Evolution: New Branches on the Alvarezsaur Tree.
Two new species of dinosaur from the mid-Cretaceous of China document previously-unknown stages in the evolutionary transition from primitive Jurassic carnivores to the highly transformed insectivorous alvarezsaurids of the Late Cretaceous.


Recent Progress in the Discovery and Development of 2-Nitroimidazooxazines and 6-Nitroimidazooxazoles to Treat Tuberculosis and Neglected Tropical Diseases.
Nitroimidazole drugs have a long history as therapeutic agents to treat bacterial and parasitic diseases. The discovery in 1989 of a bicyclic nitroimidazole lead, displaying in vitro and in vivo antitubercular activity, spurred intensive exploration of this and related scaffolds, which led to the regulatory approval of pretomanid and delamanid as a new class of tuberculosis drugs. Much of the discovery work related to this took place over a 20-year period ending in 2010, which is covered in a number of cited reviews. This review highlights subsequent research published over the 2011-August 2020 timeframe, and captures detailed structure-activity relationship studies and synthetic strategies directed towards uncovering newer generation drugs for both tuberculosis and selected neglected tropical diseases. Additionally, this review presents in silico calculations relating to the drug-like properties of lead compounds and clinical agents, as well as chemical development and manufacturing processes toward providing bulk drug supplies.


Adenosine ameliorated Aβ25-35-induced brain injury through the inhibition of apoptosis and oxidative stress via an ERα pathway.
Previous studies have shown that adenosine has estrogen-like activity mediated by estrogen receptor α (ERɑ). This study aimed to examine the effects of adenosine on Aβ25-35-induced brain injury and the underlying mechanisms involved. Adenosine (Ade, 20 mg/kg, i.g.) was administered for four weeks, followed by the induction of Alzheimer's disease (AD) by Aβ25-35 (200 µM, 3 µL/20 g, i.c.v.). Furthermore, a specific ERα blocker (MPP, 0.3 mg/kg, i.p.) was administered 30 min before the treatments of adenosine to evaluate whether the observed effects elicited by adenosine were mediated via ERα. In addition, the learning and memory ability, neuronal damage, and the levels of amyloid β-protein (Aβ), phosphorylated Tau Protein (p-Tau), apoptosis, oxidative stress, immune cells, and ERα were examined. The antagonistic effect of MPP (1 µM) against adenosine (5 µM) in Aβ25-35 (20 µM, 24 h)-induced N9 and PC-12 cells was also investigated. Adenosine improved learning and memory ability, reduced neuronal damage, downregulated Aβ42/Aβ40, p-Tau, apoptosis, and oxidative stress, transformed immune cells, and increased the expression of ERα following Aβ25-35 challenge. MPP could block these effects. Moreover, MPP also blocked the effects of adenosine on the levels of apoptosis and reactive oxygen species (ROS) in Aβ25-35-induced N9 and PC-12 cells. Adenosine ameliorated Aβ25-35-induced brain injury by inhibiting apoptosis and oxidative stress, possibly via an ERα pathway.


Treponemal antigens detected by immunoblotting with serum and CSF antibodies of neurosyphilitic patients.
Treponemal-antigen-eliciting antibodies in neurosyphilis were investigated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis immunoblotting with 17 sera and cerebrospinal fluid (CSF) (16 pairs) from 10 neurosyphilitic patients. Sera and CSF detected identical proteins. IgG antibodies in sera and CSF mainly revealed Treponema pallidum proteins of MW 48, 45, 38 and 37 Kd, and T. phagedenis proteins of MW 59, 54, 41, 40, 35 and 33 Kd. Few proteins were detected by IgM antibodies. Although no particular protein elicited antibodies specific for neurosyphilis, the immunoblot detection of antibodies to T. pallidum or T. phagedenis antigens in CSF or sera should be useful as a diagnostic tool for neurosyphilis.


A method for 3D-reconstruction of a muscle thick filament using the tilt series images of a single filament electron tomogram.
Myosin interacting-heads (MIH) motifs are visualized in 3D-reconstructions of thick filaments from striated muscle. These reconstructions are calculated by averaging methods using images from electron micrographs of grids prepared using numerous filament preparations. Here we propose an alternative method to calculate the 3D-reconstruction of a single thick filament using only a tilt series images recorded by electron tomography. Relaxed thick filaments, prepared from tarantula leg muscle homogenates, were negatively stained. Single-axis tilt series of single isolated thick filaments were obtained with the electron microscope at a low electron dose, and recorded on a CCD camera by electron tomography. An IHRSR 3D-recontruction was calculated from the tilt series images of a single thick filament. The reconstruction was enhanced by including in the search stage dual tilt image segments while only single tilt along the filament axis is usually used, as well as applying a band pass filter just before the back projection. The reconstruction from a single filament has a 40 Å resolution and clearly shows the presence of MIH motifs. In contrast, the electron tomogram 3D-reconstruction of the same thick filament - calculated without any image averaging and/or imposition of helical symmetry - only reveals MIH motifs infrequently. This is - to our knowledge - the first application of the IHRSR method to calculate a 3D reconstruction from tilt series images. This single filament IHRSR reconstruction method (SF-IHRSR) should provide a new tool to assess structural differences between well-ordered thick (or thin) filaments in a grid by recording separately their electron tomograms.


Crossed immunoelectrofocusing for identification of normal and abnormal cerebrospinal fluid proteins. A preliminary report.
Isoelectric focusing is a valuable method for the analysis of cerebrospinal fluid (CSF) proteins. Its high resolving power has, however, created problems in identifying the large number of protein bands separated. In an attempt to identify these bands, two-dimensional crossed immunoelectrofocusing has been used, where isoelectric focusing is combined with rocket immunoelectrophoresis. By these methods 9 of the normal proteins in the acidic pH interval have been identified. In addition the unusual CSF protein abnormalities occurring in Marie-Sanger-Brown's ataxia and alcoholic cerebellar degeneration have been shown to represent increases of different microheterogeneous forms of transferrin.


Using computer-extracted image phenotypes from tumors on breast magnetic resonance imaging to predict breast cancer pathologic stage.
The objective of this study was to demonstrate that computer-extracted image phenotypes (CEIPs) of biopsy-proven breast cancer on magnetic resonance imaging (MRI) can accurately predict pathologic stage. The authors used a data set of deidentified breast MRIs organized by the National Cancer Institute in The Cancer Imaging Archive. In total, 91 biopsy-proven breast cancers were analyzed from patients who had information available on pathologic stage (stage I, n = 22; stage II, n = 58; stage III, n = 11) and surgically verified lymph node status (negative lymph nodes, n = 46; ≥ 1 positive lymph node, n = 44; no lymph nodes examined, n = 1). Tumors were characterized according to 1) radiologist-measured size and 2) CEIP. Then, models were built that combined 2 CEIPs to predict tumor pathologic stage and lymph node involvement, and the models were evaluated in a leave-1-out, cross-validation analysis with the area under the receiver operating characteristic curve (AUC) as the value of interest. Tumor size was the most powerful predictor of pathologic stage, but CEIPs that captured biologic behavior also emerged as predictive (eg, stage I and II vs stage III demonstrated an AUC of 0.83). No size measure was successful in the prediction of positive lymph nodes, but adding a CEIP that described tumor "homogeneity" significantly improved discrimination (AUC = 0.62; P = .003) compared with chance. The current results indicate that MRI phenotypes have promise for predicting breast cancer pathologic stage and lymph node status. Cancer 2016;122:748-757. © 2015 American Cancer Society.


Evaluation of a high-content screening fluorescence-based assay analyzing the pharmacological modulation of lipid homeostasis in human macrophages.
For understanding cholesterol and phospholipid efflux pathways there is a need for cellular fluorescence-based high-content screens (HCS) to investigated the cholesterol and phospholipid content in human macrophages. Making use of fluorescence imaging based on HCS we have developed a tool to evaluate new agents that can act as inducers of cholesterol efflux. The fluorescence assay is based on the different staining patterns of cholesterol-loaded (E-LDL) and deloaded (HDL3) differentiated monocytes by the saturated, fluorescent lipid probe (1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine)-tetramethyl-rhodamin. Morphologic examination and statistical evaluation of the staining pattern such as gray value, threshold area, shape factor and the spot size distribution provides evidence for a significant pattern change when cholesterol enriched and cholesterol depleted differentiated monocytes were imaged.


Skeletal facial deformity in patients with β thalassemia major: Report of one Tunisian case and a review of the literature.
β Thalassemia is an inherited genetic disorder of hemoglobin synthesis characterized by a reduction of β chains of globin. Typical features of patients with β thalassemia are skeletal modifications, particularly in the skull and in the facial bones. In thalassemia major, involvement of the facial skeleton can result in severe disfigurement, often referred to as "rodent facies". Various surgical approaches to correct the facial deformity have been advocated; however, treatment remains controversial. The worse the patient's systemic condition, the more unstable and more complicated the surgical procedure. Patient with multisystemic disorder and severe deformity, such as in our case, with a complete lack of cortical bone for bone fixation, might not be amenable to such procedures. Thorough knowledge of the multiple systemic manifestations, therapy, and prognosis of this syndrome is necessary to formulate a safe, comprehensive surgical plan for these patients.


Effects of a visual task with cognitive demand on dynamic and steady-state accommodation.
Dynamic accommodative response before and after, and steady-state accommodation during, a visual task were measured using an infrared optometer to investigate the effects of psychological stress on accommodative facility. Increase in the post-task dynamic accommodation response time (for a near-to-far condition) was greater for a group of subjects given a mental task at a higher presentation speed. In addition the steady-state accommodation showed an inward shift under a closed-loop condition which was enhanced when computation time was decreased. However, an inward shift was not evident when the performance level of subjects increased following training. The relationship between psychological stress, cognitive demand and accommodative function is discussed.


Application of artificial neural networks to predict multiple quality of dry-cured ham based on protein degradation.
This study investigated protein degradation and quality changes during the processing of dry-cured ham, and then established the multiple quality prediction model based on protein degradation. From the raw material to the curing period, proteolysis index of external samples were higher than that of internal samples, however, the difference gradually decreased from the drying period to the maturing period. Protein degradation can be used as indicators for controlling quality of the hams. With protein degradation index as input variables, the back propagation-artificial neural networks (BP-ANN) models were optimized, with training function of trainlm, transfer function of logsig in input-hidden layer and tansig in hidden-output layer, and 20 hidden layer neurons. Furthermore, the relative errors of predictive data and experimental data of 12 samples were approximately 0 with the BP-ANN model. Results indicated that the BP-ANN has great potential in predicting multiple quality of dry-cured ham based on protein degradation.


Characterisation of biofilm formation by a Streptococcus suis meningitis isolate.
Biofilm formation by a strain of Streptococcus suis serotype 2 isolated from a case of meningitis in pigs was characterised. Using a polystyrene microtitre plate assay, S. suis 95-8242 produced a dense biofilm when glucose, fructose or sucrose was used as the carbohydrate source, whereas no biofilm formed in the presence of lactose. Polysaccharide production by the biofilm-forming strain was demonstrated by the Congo red agar assay. Transmission electron microscopy revealed that bacterial cells were surrounded by a thick layer of polycationic ferritin-labelled material. S. suis 95-8242 was more resistant to both penicillin G and ampicillin in biofilms than in planktonic cultures on the basis of minimal inhibitory and minimal bactericidal concentrations.


Multicentric solid pseudopapillary neoplasms of the pancreas diagnosed by endoscopic ultrasound-guided fine needle aspiration: a case report.
Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor. This neoplasm usually arises as a single mass; multicentricity is exceptionally rare. We report the preoperative diagnosis of multicentric SPNs by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). A 32-year-old woman presented to the hospital with a pancreatic tumor that was detected on abdominal echography. Contrast-enhanced computed tomography (CT) scans revealed a 5-mm low-density mass in the body of the pancreas and a 10-mm mass in the tail of the pancreas. Magnetic resonance imaging (MRI) also revealed two tumors in the body and tail of the pancreas. On endoscopic ultrasonography (EUS), two indistinct and heterogeneous echogenic masses were found, and EUS-FNA was performed for each of these tumors. Cytological analysis revealed that the two masses were highly cellular with papillary groups of small, uniform, oval cells surrounding a fibrovascular core. Immunohistochemistry was positive for α-1 antitrypsin, vimentin, neuron-specific enolase (NSE), CD10, and progesterone receptor. These features confirmed the preoperative diagnosis of multicentric SPNs. The patient underwent laparoscopic distal pancreatectomy with splenectomy. The final pathologic diagnosis was multicentric SPNs. During 2 years of follow-up, she has not developed any recurrence.


Functional heterogeneity of gut-resident regulatory T cells.
Regulatory T cells (Treg cells) have a central role in the maintenance of intestinal homeostasis by restraining inappropriate immune responses in the healthy gut. Although distinct intestinal immune cell populations have been described to exhibit regulatory activity, several genetic and functional studies provided a strong evidence for a pivotal role of forkhead box P3 (Foxp3)+CD4+ Treg cells in prevention of dysregulated mucosal immune reactions and development of chronic immunological disorders such as celiac disease, food allergies and inflammatory bowel disease. Treg cells provide an important layer of intestinal defense by suppressing immune responses against innocuous food and commensal-derived antigens. Recent functional studies suggest that Treg cells are also involved in several other processes such as controlling microbial diversity in the gut, immunoglobulin A selection and supporting tissue repair in response to intestinal tissue damage. A better understanding of the functional heterogeneity as well as of the molecular signals, which regulate distinct intestinal Treg cell subsets, will encourage strategies aimed at transplanting the optimal Treg cell subset for cellular therapy in humans.