Global versus factor-related impression of severity in Parkinson's disease: a new clinimetric index (CISI-PD).
In Parkinson's disease (PD), the Clinical Global Impression of Severity (CGIS) is often used as an additional outcome in clinical trials. It is hypothesized that this measure summarizes clinical assessment and is mainly influenced by the rating of four domains, namely, motor signs, disability, motor complications, and cognitive impairment. Ratings of these four factors were combined to form a new Clinical Impression of Severity Index for Parkinson's Disease (CISI-PD). A sample of 150 PD patients was evaluated using the following scales: Hoehn and Yahr staging, Schwab and England scale, Unified Parkinson's Disease Rating Scale, Scales for Outcomes in Parkinson's Disease-Motor Scale, CGIS, and CISI-PD. The results show that the CGIS is closely related to the above-mentioned measures (r=0.49-0.89). CISI-PD correlation with these scales was very similar (r=0.55-0.91), to the extent that the difference between corresponding coefficients was systematically less than 0.10. A multiple regression model showed that 92% of the CIGS variance was explained by the four CISI-PD items. Finally, the CISI-PD displayed adequate psychometric properties, with satisfactory internal consistency (alpha=0.90) and convergent (r>0.75) and known-groups validity. The CISI-PD is a valid and reliable measure that expands the information obtained via the CGIS.


Is there any association between subcutaneous adipose tissue area and plasma total and high molecular weight adiponectin levels?
This study was conducted for the purpose of clarifying the correlations between the subcutaneous adipose tissue area and plasma total and high-molecular weight (HMW) adiponectin levels. The subjects of this study comprised 359 men and 142 women who underwent general health examinations from October 2005 to December 2006. The abdominal subcutaneous and visceral adipose tissue areas were measured using low-dose x-ray computed tomography. Total and HMW adiponectin levels were measured using the enzyme-linked immunosorbent assay system based on a monoclonal antibody to humans. There were negative correlations between the plasma total and HMW adiponectin levels and visceral and subcutaneous adipose tissue areas using simple correlation analysis. Multiple linear regression analysis clearly indicated that the subcutaneous adipose tissue area was independently correlated with the HMW adiponectin levels in men and closely related in women. Many studies reported that only the visceral adipose tissue area showed a significant correlation with metabolic syndrome. However, these results clearly indicate that it is also important to consider the subcutaneous adipose tissue area in metabolic syndrome.


Reducing diarrhoea in an adult surgical intensive care unit: A quality improvement study.
Although diarrhoea is a real source of morbidity for critically ill patients, this issue has been little studied, making it difficult to understand its mechanisms and management. We conducted a quality improvement study in an adult surgical intensive care unit before/after the implementation of a specific protocol to firstly improve diarrhoea management for patient benefit and secondly to understand the impact on caregivers. The first part of this before/after study consisted in assessing the proportion of patients receiving an anti-diarrheal treatment before (phase I)/after (phase II) the implementation of the protocol. The second part of the study was to survey the caregivers on this topic. Sixty four adults were included (33 in phase I; 31 in phase II) with 280 diarrheal episodes (129 in phase I; 151 in phase II). The proportion of patients who received at least one anti-diarrheal treatment was similar between the two phases (79% (26/33) vs. 68% (21/31), p = .40). Diarrhoea incidence was also similar (9% (33 patients/368 admissions) vs. 11% (31 patients/275 admissions), p = .35). The delay to initiate at least one treatment was significantly shorter in phase II (2 days [1-7] vs. 0 day [0-2]; p < .001). The patients' rehabilitation was no longer impacted by the occurrence of a diarrheal episode in phase II (39% (13/33) vs. 0% (0/31), p < .001). Eighty team members completed the surveys in phase I and 70 in phase II. Caregivers perceived diarrhoea like a burden and its economic impact remained high. The implementation of a protocol for the management of ICU diarrhoea did not increase the proportion of patients treated, but it did significantly improve the delay to initiate a treatment. The patients' rehabilitation was no longer affected by diarrhoea. The use of specific anti-diarrhoea guidelines may help to reduce the burden of diarrhoea in an ICU.


Effect of hydrocortisone and interleukins 1 and 2 on eosinophil progenitors in hypereosinophilic states.
The growth of eosinophil progenitors (CFU-Eo) and its modulation by hydrocortisone (HC), mononuclear cells, interleukin 1 (IL-1), and interleukin 2 (IL-2) in three cases of eosinophilia are reported in this paper. One microM HC decreased the proportion of CFU-Eo in each of these three patients, and in each case, the addition of autologous mononuclear cells at a 1:1 ratio abrogated the effect of HC on CFU-Eo. As studied in two of the three cases, IL-1 and IL-2 were able to prevent the effect of HC. Further studies showed no effect of HC when monocyte T cell-depleted marrow cells were used as the target population. These results suggest that CFU-Eo production in eosinophilic states is subject to modulation by HC and T lymphocytes.


HB-EGF is associated with DNA damage and Mcl-1 turnover in human glioma cell lines treated by Temozolomide.
Temozolomide (TMZ) is the main chemotherapeutic agent used for treating newly diagnosed Glioblastoma Multiforme (GBM), the most frequent malignant brain tumors in adults. This alkylating agent induces DNA double strand breaks (DSBs) which in turn lead to apoptosis by activating the Bcl-2 controlled mitochondrial pathway. However, GBM invariably recur as tumors become resistant to TMZ. We investigated the implication of EGFR ligands in this resistance and we found that the pro Heparin Binding Epidermal Growth Factor (proHB-EGF) expression is linked to the early response to TMZ in human glioma cell lines. However, HB-EGF does not affect apoptosis per se although its expression is associated with the degradation of Mcl-1. HB-EGF is implicated in DSBs repair as silencing of HB-EGF increased γH2AX foci half-life as well as USP9X expression, two features that could be linked to the observed effect on Mcl-1. Our data demonstrate a new role for HB-EGF in TMZ treated cell lines.


Oral melanoma with oral squamous carcinoma: report of a case.
A case of an oral melanoma occurring simultaneously with an oral squamous carcinoma has been presented. This combination is not thought to have been reported in the literature before. The histologic diagnosis is discussed as are the incidence, prognosis, and possible treatment of oral melanoma.


Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys.
The addition of the synthetic progestin medroxyprogesterone acetate (MPA) to postmenopausal estrogen therapy significantly increases breast cancer risk. Whether this adverse effect is specific to MPA or characteristic of all progestogens is not known. The goal of this study was to compare the effects of oral estradiol (E2) given with either MPA or micronized progesterone (P4) on risk biomarkers for breast cancer in a postmenopausal primate model. For this randomized crossover trial, twenty-six ovariectomized adult female cynomolgus macaques were divided into social groups and rotated randomly through the following treatments (expressed as equivalent doses for women): (1) placebo; (2) E2 (1 mg/day); (3) E2 + P4 (200 mg/day); and (4) E2 + MPA (2.5 mg/day). Hormones were administered orally, and all animals were individually dosed. Treatments lasted two months and were separated by a one-month washout period. The main outcome measure was breast epithelial proliferation, as measured by Ki67 expression. Compared to placebo, E2 + MPA resulted in significantly greater breast proliferation in lobular (P < 0.01) and ductal (P < 0.01) epithelium, while E2 + P4 did not. Intramammary gene expression of the proliferation markers Ki67 and cyclin B1 was also higher after treatment with E2 + MPA (P < 0.01) but not E2 + P4. Both progestogens significantly attenuated E2 effects on body weight, endometrium, and the TFF1 marker of estrogen receptor activity in the breast. These findings suggest that oral micronized progesterone has a more favorable effect on risk biomarkers for postmenopausal breast cancer than medroxyprogesterone acetate.


Survival analysis of patients with subglottic squamous cell carcinoma based on the SEER database.
This study aimed to investigate the demographic and clinicopathological characteristics, and survival outcomes of subglottic Squamous Cell Carcinoma (SCC) based on the Surveillance, Epidemiology, and End Results (SEER) database. Demographic and clinicopathological information, including age, sex, race, tumor size, histologic grade, clinical/TNM stage, tumor invasion extent, Lymph Node Metastasis (LNM) extent, size of metastatic lymph nodes, LNM ratio and treatment data, of 842 subglottic SCC patients diagnosed between 1996 and 2016 were acquired. Kaplan-Meier survival analyses were performed to assess the effects of clinicopathological characteristics, treatment modalities, surgical procedures, and adjuvant therapies on overall survival and cancer-specific survival. Subglottic SCC was more frequent among males aged 60-70 years, with low-grade but locally advanced lesions without local or distant metastases. Age and several primary tumor/LNM related variables were independent risk factors for overall survival and cancer specific survival. Advanced-stage and high-grade disease led to unfavorable prognosis. The most common treatment modality and surgical procedure were surgery plus radiotherapy and total laryngectomy, respectively. Surgery plus radiotherapy provided favorable 5-year survival outcomes, while total laryngectomy had the worst. Surgery plus adjuvant therapy showed better survival outcomes than surgery alone. This study confirmed the rarity of subglottic SCC. Patients with subglottic SCCs suffered poor prognosis especially for those with advanced-stage or high-grade lesions. The prognosis of subglottic SCC remained poor over the years, despite recent progress in cancer therapies. Surgery plus adjuvant therapy improved the survival outcome. Although larynx preservation surgery was beneficial for early-stage disease, total laryngectomy was favored for patients with advanced tumors. Level 4.


On the mutagenic and recombinogenic activity of certain herbicides in Salmonella typhimurium and in Aspergillus nidulans.
The plant growth-regulating hormones indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA), both strong recombinogens in Aspergillus nidulans, were tested in Salmonella typhimurium strains for his revertants at a range of concentrations from 1 to 2000 micrograms/plate with and without metabolic activation and were found negative. Also 3 herbicides of the chlorophenoxy group, 2,4-(dichlorophenoxy)acetic acid (2,4-D), 2,4-(dichlorophenoxy)butyric acid (2,4-DB) and 4-chloro-2-methylphenoxyacetic acid (MCPA), which show a plant growth hormone-like activity, and 2 of the triazine group, 2-ethylamino-4-chloro-6-isopropylamino-1,3,5-triazine (atrazine) and 2,4-bis(isopropylamino)6-chloro-1,3,5-triazine (propazine) were tested in S. typhimurium for point mutations and in A. nidulans for mitotic recombination. 2,4-D and MCPA were found to be weakly mutagenic at concentrations between 250 and 750 micrograms/plate in strain TA97a and only after metabolic activation and were recombinogens by inducing mainly mitotic crossing-over in A. nidulans at concentrations of 4-48 microM and 1500-3000 microM, respectively. 2,4-DB, atrazine and propazine were negative in both the Ames and the Aspergillus tests.


Estimating down deadwood from FIA forest inventory variables in Maine.
Down deadwood (DDW) is a carbon component important in the function and structure of forest ecosystems, but estimating DDW is problematic because these data are not widely available in forest inventory databases. However, DDW data were collected on USDA Forest Service Forest Inventory and Analysis (FIA) plots during Maine's 1995 inventory. This study examines ways to predict DDW biomass from other FIA variables so that DDW could be estimated without tedious measurement. Our results include a regression model that predicts DDW as a function of stand size class, basal area of dead and cut trees, and dummy variables for forest type and forest industry ownership. We also found DDW similar to FIA's standing-tree mortality at a statewide scale.


Changes in serum proteins and in major liver constituents following carbon tetrachloride and a high-fat choline-free diet in rats.
Both carbon tetrachloride and a high-fat, low-protein choline-free diet cause hepatomegaly in rats due to an accumulation of both lipids and proteins with a concomitant increase in deoxyribonucleic acid content. CCl4 causes a decline in hepatic glycogen. Serum albumin level is decreased in CCl4-treated rats and increased in those fed the experimental diet.


CardioBengo study protocol: a population based cardiovascular longitudinal study in Bengo Province, Angola.
Cardiovascular diseases and other non-communicable diseases are major causes of morbidity and mortality, responsible for 38 million deaths in 2012, 75 % occurring in low- and middle-income countries. Most of these countries are facing a period of epidemiological transition, being confronted with an increased burden of non-communicable diseases, which challenge health systems mainly designed to deal with infectious diseases. With the adoption of the World Health Organization "Global Action Plan for the Prevention and Control of non-communicable diseases, 2013-2020", the national dimension of risk factors for non-communicable diseases must be reported on a regular basis. Angola has no national surveillance system for non-communicable diseases, and periodic population-based studies can help to overcome this lack of information. CardioBengo will collect information on risk factors, awareness rates and prevalence of symptoms relevant to cardiovascular diseases, to assist decision makers in the implementation of prevention and treatment policies and programs. CardioBengo is designed as a research structure that comprises a cross-sectional component, providing baseline information and the assembling of a cohort to follow-up the dynamics of cardiovascular diseases risk factors in the catchment area of the Dande Health and Demographic Surveillance System of the Health Research Centre of Angola, in Bengo Province, Angola. The World Health Organization STEPwise approach to surveillance questionnaires and procedures will be used to collect information on a representative sex-age stratified sample, aged between 15 and 64 years old. CardioBengo will recruit the first population cohort in Angola designed to evaluate cardiovascular diseases risk factors. Using the structures in place of the Dande Health and Demographic Surveillance System and a reliable methodology that generates comparable results with other regions and countries, this study will constitute a useful tool for the surveillance of cardiovascular diseases. Like all longitudinal studies, a strong concern exists regarding dropouts, but strategies like regular visits to selected participants and a strong community involvement are in place to minimize these occurrences.


Importance of the posterior bundle of the medial ulnar collateral ligament.
There has been a renewed interest in the pathomechanics of elbow dislocation, with recent literature having suggested that the medial ulnar collateral ligament is more often disrupted in dislocations than the lateral ligamentous complex. The purpose of this serial sectioning study was to determine the influence of the posterior bundle of the medial ulnar collateral ligament (pMUCL) as a stabilizer against elbow dislocation. An elbow dislocation was simulated in 5 cadaveric elbows by mechanically applying an external rotation moment and valgus force. Medial ulnohumeral joint gapping was measured at 30°, 60°, and 90° of flexion in an intact elbow after sectioning of the medial collateral ligament's anterior bundle (aMUCL) and then after sectioning of the pMUCL as well. After sectioning of the aMUCL, the pMUCL was able to stabilize the joint against dislocation. After aMUCL sectioning, the proximal joint space significantly increased by 4.2 ± 0.6 mm at 30° of flexion and 2.6 ± 0.3 mm at 60° of flexion, although it did not dislocate. The gapping increase of 0.9 ± 0.6 at 90° of flexion did not reach significance. After sectioning of the pMUCL (after having already sectioned the aMUCL), all of the specimens frankly dislocated at all flexion angles. An intact pMUCL can prevent elbow dislocation and limited joint subluxation to within 6.6 mm. Our findings indicate that repair or reconstruction may be warranted in certain circumstances (ie, residual instability after operative management of a terrible triad injury or after aMUCL reconstruction).


Medical care expenditures associated with chronic kidney disease in adults with diabetes: United States 2011.
Approximately 1 in 3 adults with diabetes have CKD. However, there are no recent national estimates of the association of CKD with medical care expenditures in individuals with diabetes. Our aim is to assess the association of CKD with total medical expenditures in US adults with diabetes using a national sample and novel cost estimation methodology. Data on 2,053 adults with diabetes in the 2011 Medical Expenditure Panel Survey (MEPS) was analyzed. Individuals with CKD were identified based on self-report. Adjusted mean health services expenditures per person in 2011 were estimated using a two-part model after adjusting for demographic and clinical covariates. Of the 2,053 individuals with diabetes, approximately 9.7% had self-reported CKD. Unadjusted mean expenditures for individuals with CKD were $20,726 relative to $9,689.49 for no CKD. Adjusted mean expenditures from the 2-part model for individuals with CKD were $8473 higher relative to individuals without CKD. Additional significant covariates were Hispanic/other race, uninsured, urban dwellers, CVD, stroke, high cholesterol, arthritis, and asthma. The estimated unadjusted total expenditures for individuals with CKD were estimated to be in excess of $43 billion in 2011. We showed that CKD is a significant contributor to the financial burden among individuals with diabetes, and that minorities and the uninsured with CKD may experience barriers in access to care. Our study also provides a baseline national estimate of CKD cost in Diabetes by which future studies can be used for comparison.


Rapid detection of bacteria that produce extended-spectrum β-lactamase by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Proper use of antibacterial agents is necessary to prevent the spread of drug-resistant bacteria. To support clinicians, laboratories need to rapidly determine bacterial drug susceptibility/resistance. We have established a method to distinguish extended-spectrum β-lactamase (ESBL)-producing clinical isolates by capturing structural changes in β-lactam antibiotics using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Clinical isolates of Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis, classified into ESBL-producing strains and sensitive strains based on the presence or absence of a CTX-M-type gene, were used. Test bacteria were cultured aerobically in solid-phase wells of Eiken DPD1 dry plates at 35°C for 15 min or 30 min with the antibiotics cefotaxime (CTX), cefpodoxime (CPDX) or piperacillin (PIPC). Culture supernatants were then used for analysis with a MALDI Biotyper. Signals derived from non-hydrolyzed products of antibiotics were observed in all strains. In the case of ESBL-producing strains, signals derived from the hydrolysis products of antibiotics were also observed. Since the ratio of signal intensity derived from hydrolysis products divided by the total signal intensity detected was ≥11% for CTX and ≥6% for CPDX and PIPC, all strains were determined to be ESBL-producing bacteria. The short incubation time of 15 min suggests that this method can identify ESBL-producing strains much more rapidly than conventional methods.


Ureterovesical fistula: an unusual complication of ureteral reimplantation.
A case of a ureterovesical fistula secondary to ureteral reimplantation is presented. The factors that may have contributed to formation of the fistula are discussed, and the diagnosis and management of this complication are reviewed.


Development and reproduction of Panonychus citri (Prostigmata: Tetranychidae) on different species and varieties of citrus plants.
The species and varieties of citrus plants that are currently grown can favor the population growth of the citrus red mite Panonychus citri (McGregor) (Prostigmata: Tetranychidae) and alter the pest management programs in citrus groves. In this study we evaluated, in the laboratory, the development and reproduction of P. citri and estimated its life table parameters when reared on four varieties of Citrus sinensis (L.) Osbeck (Valencia, Pera, Natal, and Hamlin), one variety of Citrus reticulata Blanco (Ponkan) and one variety of Citrus limon (L.) Burm. (Sicilian). The incubation period and egg viability were not affected by the host plant. However, the development and survival of the immature stage were significantly lower on Hamlin orange than on Valencia, Pera and Natal oranges, Ponkan mandarin and Sicilian lemon. The fecundity and oviposition period of females were lower on Hamlin orange than on the other hosts. Mites reared on Valencia orange and Sicilian lemon had a higher net reproductive rate (R 0 ), intrinsic growth rate (r) and finite rate of increase (λ), and a shorter interval between generations (T) than on Pera, Natal and Hamlin oranges and Ponkan mandarin. On the other hand, mites reared on Hamlin orange had the lowest R 0 , r and λ and the highest T among the hosts. Based on the results obtained we recommend that for Valencia orange and Sicilian lemon, the mite monitoring programs should be more intense to detect the initial infestation of pest, avoiding the damage in plants and the increase in production costs.


Quantitative sputum analysis: neuraminidase and tuberculosis.
Clinically sensitive screening tests for pulmonary tuberculosis. Quantitation of sputum lysosomal enzymes derived from mycobacterium-infected macrophage. Neuraminidase in culture-positive sputa exemplifies such systems. Correlation coefficient between sputum neuraminidase values (n=18), obtained by fixed-volume samplers and variable volume micropipets, was 0.995. Mean sputum neuraminidase values among tuberculous (137) and non-tuberculous (117) patients were 15.08 and 0.90 mU per mL. Medians were 8.45 and 0.20 mU per mL. Non-parametric analysis concludes a significant difference between the groups at P<0.001. Sputum neuraminidase levels above 1.0 mU per mL characterized 126 of 137 tuberculosis patients (92.0%). (1) Calibrated sputum fluid samplers facilitate quantitation of sputum enzymes. (2) Sputum neuraminidase levels over 1.0 mU per mL associate with Mycobacterium tuberculosis in 92% of cases. (3) Sputum neuraminidase measurements offer a screening procedure with which to identify samples for more specific, but less sensitive tests.


Establishment and validation of a competitive risk model for predicting cancer-specific survival in patients with osteosarcoma: a population-based study.
Osteosarcoma is the most common primary bone tumor with a poor prognosis. The aim of this study was to establish a competitive risk model nomogram to predict cancer-specific survival in patients with osteosarcoma. Patient data was obtained from the Surveillance, Epidemiology, and End Results database in the United States. A sub-distribution proportional hazards model was used to analyze independent risk factors affecting cancer-specific mortality (CSM) in osteosarcoma patients. Based on these risk factors, a competitive risk model was constructed to predict 1-year, 3-year, and 5-year cancer-specific survival (CSS) in osteosarcoma patients. The reliability and accuracy of the nomogram were evaluated using the concordance index (C-index), the area under the receiver operating characteristic curve (AUC), and calibration curves. A total of 2900 osteosarcoma patients were included. The analysis showed that age, primary tumor site, M stage, surgery, chemotherapy, and median household income were independent risk factors influencing CSM in patients. The competitive risk model was constructed to predict CSS in osteosarcoma patients. In the training and validation sets, the C-index of the model was 0.756 (95% CI 0.725-0.787) and 0.737 (95% CI 0.717-0.757), respectively, and the AUC was greater than 0.7 for both. The calibration curves also demonstrated a high consistency between the predicted survival rates and the actual survival rates, confirming the accuracy and reliability of the model. We established a competitive risk model to predict 1-year, 3-year, and 5-year CSS in osteosarcoma patients. The model demonstrated good predictive performance and can assist clinicians and patients in making clinical decisions and formulating follow-up strategies.


Penile blood pressure in the evaluation of erectile impotence.
Identification of specific etiologies of erectile impotence is hindered by a paucity of objective criteria needed to segregate organic from psychogenic varieties and to define specific organic causes. Simplified measurement of penile blood pressure was performed with a digital cuff and a portable ultrasound Doppler system for flow detection. An index relating penile-to-brachial systolic blood pressure was generated, and the results were compared in patients with impotence versus patients with normal erections. The mean indices for the two groups were significantly different (P less than 0.05). The penile-to-brachial index provides an additional diagnostic tool in the evaluation of potency, allowing us to identify those patients with decreased penile blood flow, and may be helpful in selecting patients for revascularization procedures.


Postnatal ontogeny of Neuromedin S and its receptors NMUR1 and NMUR2 expression in mouse testis.
Neuromedin S (NMS) is a well-known anorexigenic neuropeptide. Despite some reports of the presence of its transcript and precursor protein in testis, the expression and localization of NMS and its receptors during the postnatal development of mammalian testis remains elusive. We investigated the expression patterns and testicular localization of NMS and its receptors NMUR1 and NMUR2, during 5, 10, 20, 30, and 90 days of postnatal development, using real time PCR, immunoblot analysis and immunohistochemistry in mice. NMS and its receptors are present at all age groups at transcript level in mouse testis. At the protein level, NMS and NMUR2 are present in all age groups, whereas NMUR1 is present primarily in 30- and 90-day testis. Immunolocalization study showed that NMS and NMUR2 are expressed in spermatogonia, spermatocytes, Sertoli cells, and Leydig cells, in contrast to NMUR1 which is expressed exclusively in the Leydig cells of 30- and 90-day testis. The results also confirm the intranuclear localization of NMS in spermatogonia and spermatocytes. Although NMS-NMUR2 is expressed in Sertoli cells at all stages of the spermatogenic cycle, they showed a stage-specific expression pattern in spermatogonia and primary spermatocytes. In conclusion, NMS and its receptors NMUR1 and NMUR2 are expressed in the testis and may regulate spermatogenesis, possibly by modulating steroidogenesis and Sertoli cell function in the testis.


The social context of imitation in infancy.
Infants increasingly generalize deferred imitation across environmental contexts between 6 and 18 months of age. In three experiments with 126 6-, 9-, 12-, 15-, and 18-month-olds, we examined the role of the social context in deferred imitation. One experimenter demonstrated target actions on a hand puppet, and a second experimenter tested imitation 24h later. When the second experimenter was novel, infants did not exhibit deferred imitation at any age; when infants were preexposed to the second experimenter, all of them did. Imitating immediately after the demonstration also facilitated deferred imitation in a novel social context at all ages but 6 months. Infants' pervasive failure to exhibit deferred imitation in a novel social context may reflect evolutionary selection pressures that favored conservative behavior in social animals.


Ca2+ transients in cardiac myocytes measured with high and low affinity Ca2+ indicators.
Intracellular calcium ion ([Ca2+]i) transients were measured in voltage-clamped rat cardiac myocytes with fura-2 or furaptra to quantitate rapid changes in [Ca2+]i. Patch electrode solutions contained the K+ salt of fura-2 (50 microM) or furaptra (300 microM). With identical experimental conditions, peak amplitude of stimulated [Ca2+]i transients in furaptra-loaded myocytes was 4- to 6-fold greater than that in fura-2-loaded cells. To determine the reason for this discrepancy, intracellular fura-2 Ca2+ buffering, kinetics of Ca2+ binding, and optical properties were examined. Decreasing cellular fura-2 concentration by lowering electrode fura-2 concentration 5-fold, decreased the difference between the amplitudes of [Ca2+]i transients in fura-2 and furaptra-loaded myocytes by twofold. Thus, fura-2 buffers [Ca2+]i under these conditions; however, Ca2+ buffering is not the only factor that explains the different amplitudes of the [Ca2+]i transients measured with these indicators. From the temporal comparison of the [Ca2+]i transients measured with fura-2 and furaptra, the apparent reverse rate constant for Ca2+ binding of fura-2 was at least 65s-1, much faster than previously reported in skeletal muscle fibers. These binding kinetics do not explain the difference in the size of the [Ca2+]i transients reported by fura-2 and furaptra. Parameters for fura-2 calibration, Rmin, Rmax, and beta, were obtained in salt solutions (in vitro) and in myocytes exposed to the Ca2+ ionophore, 4-Br A23187, in EGTA-buffered solutions (in situ). Calibration of fura-2 fluorescence signals with these in situ parameters yielded [Ca2+]i transients whose peak amplitude was 50-100% larger than those calculated with in vitro parameters. Thus, in vitro calibration of fura-2 fluorescence significantly underestimates the amplitude of the [Ca2+]i transient. These data suggest that the difference in amplitude of [Ca2+]i transients in fura-2 and furaptra-loaded myocytes is due, in part, to Ca2+ buffering by fura-2 and use of in vitro calibration parameters.


Rise of multiple insecticide resistance in Anopheles funestus in Malawi: a major concern for malaria vector control.
Deciphering the dynamics and evolution of insecticide resistance in malaria vectors is crucial for successful vector control. This study reports an increase of resistance intensity and a rise of multiple insecticide resistance in Anopheles funestus in Malawi leading to reduced bed net efficacy. Anopheles funestus group mosquitoes were collected in southern Malawi and the species composition, Plasmodium infection rate, susceptibility to insecticides and molecular bases of the resistance were analysed. Mosquito collection revealed a predominance of An. funestus group mosquitoes with a high hybrid rate (12.2 %) suggesting extensive species hybridization. An. funestus sensu stricto was the main Plasmodium vector (4.8 % infection). Consistently high levels of resistance to pyrethroid and carbamate insecticides were recorded and had increased between 2009 and 2014. Furthermore, the 2014 collection exhibited multiple insecticide resistance, notably to DDT, contrary to 2009. Increased pyrethroid resistance correlates with reduced efficacy of bed nets (<5 % mortality by Olyset(®) net), which can compromise control efforts. This change in resistance dynamics is mirrored by prevalent resistance mechanisms, firstly with increased over-expression of key pyrethroid resistance genes (CYP6Pa/b and CYP6M7) in 2014 and secondly, detection of the A296S-RDL dieldrin resistance mutation for the first time. However, the L119F-GSTe2 and kdr mutations were absent. Such increased resistance levels and rise of multiple resistance highlight the need to rapidly implement resistance management strategies to preserve the effectiveness of existing insecticide-based control interventions.


Analysis of predisposing factors for type III endoleaks from directional branches after branched endovascular repair for thoracoabdominal aortic aneurysms.
Mid-term durability of branches has already been established, and BF-branched and fenestrated endovascular repair has shown comparable results with open repair in the treatment of thoracoabdominal aortic aneurysms (TAAAs). Nevertheless, target vessel instability remains the most frequent adverse event after complex endovascular aortic repair. Type III endoleaks from directional branches have been reported with a low incidence, but risk factors for this complication have not been investigated yet. This was a dual-center observational retrospective cohort study. Data were collected prospectively for each patient treated with branched endovascular repair between April 2008 and December 2019. The primary outcome was to assess potential risk factors for branch disconnection and fracture. A logistic regression analysis was performed, including preoperative and postoperative measurements as well as intraoperative details. A Cox regression hazard analysis was performed to evaluate the influence of preoperative aneurysm diameter and target vessel angulation on the outcome during follow-up. Two hundred ninety-five target visceral vessels (TVVs) in 91 patients were considered suitable for cannulation. Technical success was 96.9% (286/295 TVVs). The median follow-up was 32.5 months (interquartile range, 14.2-50.1 months). Twelve type III endoleaks from directional branches were detected (4.2%; 5 bridging stent graft fractures and 7 disconnections). Five type III endoleaks involved the celiac trunk (one fracture and four disconnections), five the superior mesenteric artery (four fractures and one disconnection), and two the renal arteries (both disconnections). The median time to type III endoleak was 22.2 months (interquartile range, 10.9-37.6 months). Preoperative TAAA diameter (P = .028), preoperative TVV angulation (P = .037), the use of a BeGraft stent graft as bridging stent graft (P = .001), and different stent types on the same vessel (P = .048) were associated with type III endoleak at univariable analysis. Using a BeGraft stent graft (P = .010) was the only significant factor predisposing to type III endoleak at multiple logistic regression. The Cox regression analysis showed a two-fold increased risk for type III endoleak for every 10-mm increase in preoperative TAAA diameter (hazard ratio, 2.00; 95% confidence interval, 1.08-3.72; P = .028) and a 1.5 increased risk every 12° increase of preoperative TVV angulation (hazard ratio, 1.47; 95% confidence interval, 1.02-2.10; P = .037). Type III endoleaks from directional branches are a non-negligible complication after branched endovascular repair, with a relevant incidence. They tended to be clustered on specific patients, and aneurysm diameter and TVV angulation are strictly associated with the outcome. Different stent types on the same vessel should be avoided whenever possible. An intensified follow-up should be adopted for patients with large aneurysms, implanted with first-generation BeGraft, or who have been already diagnosed with type III endoleaks.


Self-reported reproductive outcomes among male and female 1991 Gulf War era US military veterans.
Following the 1991 Gulf War, some veterans expressed concerns regarding their reproductive health. Our objective was to assess whether an association exists between deployment to the 1991 Gulf War and self-reported adverse pregnancy outcomes. Using a modified Dillman technique with telephone follow-up, we conducted a survey via a postal questionnaire from February 1996-August 1997 to compare selected reproductive outcomes among 10,000 US veterans deployed to the 1991 Gulf War with those of 10,000 nondeployed Gulf War era veterans. A total of 8742 individuals responded to the survey, a response rate of 51 percent. Using multivariable analyses, results showed no differences in number of reported pregnancies between Gulf War veterans and nondeployed veterans. Among 2233 female and 2159 male participants, there were no differences in birth weight of infants born to Gulf War veterans compared with nondeployed Gulf War era veterans. In multivariable models, male and female Gulf War veterans did not significantly differ in risk for ectopic pregnancies, stillbirths, or miscarriages when compared with nondeployed veterans of the same era. These results do not suggest an association between service in the 1991 Gulf War and adverse reproductive outcomes for both male and female veterans during the 4 years after the war.


Potential markers that complement expression of CA125 in epithelial ovarian cancer.
When ovarian carcinoma is diagnosed in stage I, up to 90% of patients can be cured with surgery and currently available chemotherapy. At present, less than 25% of cases are diagnosed at this stage. To increase the fraction of ovarian cancers detected at an early stage, screening strategies have been devised that utilize a rising serum CA125 level to trigger the performance of transvaginal sonography. One limitation of CA125 as an initial step in such a screening strategy is that up to 20% of ovarian cancers lack expression of the antigen. Serum tumor markers that can be detected in ovarian cancers that lack CA125 expression might improve the sensitivity for early detection. From 296 ovarian cancers, 65 (22%) were found to have weak or absent CA125 expression on immunoperoxidase staining. Tissue expression of CA125 was compared to serum CA125 levels. Using immunoperoxidase staining of tissue arrays, we have assessed expression of 10 potential serum tumor markers in the 65 epithelial ovarian cancers with little or no CA125 expression and in ovarian cystadenomas, tumors of low malignant potential, normal ovaries, and 16 other normal tissues. Low or absent expression of CA125 in surgical specimens of epithelial ovarian cancer was associated with low levels of serum CA125 in pre-operative serum specimens. In ovarian cancers that lacked CA125, all specimens (100%) expressed human kallikrein 10 (HK10), human kallikrein 6 (HK6), osteopontin (OPN), and claudin 3. A smaller fraction of CA125-deficient ovarian cancers expressed DF3 (95%), vascular endothelial growth factor (VEGF) (81%), MUC1 (62%), mesothelin (MES) (34%), HE4 (32%), and CA19-9 (29%). When reactivity with normal tissues was considered, however, MES and HE4 showed the greatest specificity. Differential expression was also found for HK10, OPN, DF3, and MUC1. At the level of tissue expression, each of 10 potential serum markers could be detected in 29-100% of ovarian cancers that had low or absent expression of CA125. Several markers exhibited more intense expression in cancers than in normal organs. Further investigation is needed to demonstrate complementary expression of markers in serum.


Pacemaker-twiddler's syndrome: a rare cause of lead displacement and pacemaker malfunction.
Pacemaker-twiddler's syndrome is characterized by spontaneous, subconscious, inadvertent, or deliberate rotation of the pulse generator by the patient resulting in lead dislodgement and pacemaker malfunction. We present a case of pacemaker-twiddler's syndrome that involved an atrioventricular sequential pacemaker. It resulted in failure of atrial lead capture and phrenic nerve stimulation but without loss of ventricular lead capture. A search of the literature revealed only ten previous cases reported; none were in the emergency medicine literature, and none involved an atrioventricular sequential pacemaker.


Detection of Plasmodium falciparum using a cloned DNA probe: a simple procedure suitable for field application.
A simple procedure was developed for spotting blood samples directly onto nylon membrane filter, without the necessity to treat samples with pronase or proteinase K, followed by hybridizing with 32P-labelled DNA probe, pUNK1-45. This probe detected specifically P. falciparum DNA and did not cross react with DNA from man, P. knowlesi, P. chabaudi or P. cynomolgi. The probe was sensitive to detect a parasitemia of 0.001% in 20 microliters of blood.


Responses of substantia nigra neurones to noxious stimulation.
Experiments were performed to determine whether substantia nigra neurones respond to noxious stimulation. Some nigral neurones were found to respond to both noxious radiant heat and intra-arterially administered bradykinin. Most nociceptive neurones were excited by noxious stimulation although some exhibited a reduction in firing rate. Following the injection of bradykinin, responses to noxious heat were reduced in magnitude for periods of up to an hour. These results show that some nigral neurones are nociceptive and provide further support for the suggestion that dopamine is involved in nociceptive mechanisms. In addition it is suggested that bradykinin may represent a rather gross of non-specific form of noxious stimulation.


The identification of 4-methylamphetamine and its synthesis by-products in forensic samples.
During the analysis of street samples for the suspected presence of controlled drugs, two samples were found to contain 4-methylamphetamine (4-MA). This is the first report of the drug in Ireland as previously only N-methylamphetamine (N-MA) had been encountered. In Ireland, little attention had previously been paid to the possible presence of the isomeric forms of methylamphetamine in submitted samples. Two street level samples were analyzed and the presence of 4-MA was confirmed in both, the other major components of these samples were examined to establish the possible synthetic route employed. The identification of a single synthetic route which accounted for the major components found in the street samples has implications for previously thought route specific analogous compounds of 4-MA. The three ring substituted isomers of methylamphetamine, namely 2-, 3- and 4-MA, were synthesized and characterized by GCMS, HR-ESIMS, NMR and IR for use as reference standards.


[A systems theory approach to the solution of the Bieri trilemma].
Psychosomatic theories reach at the question about the mind-body problem some difficulties, which are resumed in the trilemma of Bieri. We propose a solution of the implicated contradictions with a systemic approach.


PRMT1 promotes extracellular matrix degradation and apoptosis of chondrocytes in temporomandibular joint osteoarthritis via the AKT/FOXO1 signaling pathway.
Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative joint disease characterized by extracellular matrix (ECM) degradation and chondrocyte apoptosis. The aim of this study was to investigate the role of PRMT1 in TMJOA pathogenesis and its underlying molecular mechanism. Compared to the control group, PRMT1 was highly expressed in IL-1β-treated chondrocytes and articular cartilage following MIA injection into rat TMJs. Furthermore, knocking down PRMT1 considerably inhibited ECM degradation and apoptosis induced by IL-1β. Mechanistic analyses further revealed that PRMT1 knockdown activated the PI3K/AKT signaling pathway and prevented FOXO1 from translocating to the nucleus. Moreover, an inhibitor of AKT (LY294002) rescued the effect of PRMT1 knockdown on IL-1β-induced ECM degradation and apoptosis, and AMI-1, a selective inhibitor of PRMT1, inhibited PRMT1 expression and reversed the pathological progress of TMJOA. Thus, our findings suggest that PRMT1 plays an essential role in ECM degradation and chondrocyte apoptosis in TMJOA via the AKT/FOXO1 signaling pathway.


Anemia, iron deficiency, and thalassemia among the Thai population inhabiting at the Thailand-Lao PDR-Cambodia triangle.
Anemia is a major public health problem in many areas of Southeast Asia. Ascertaining anemia and defining its underlying causes is essential for providing appropriate care, management, and establishment of a control program. Limited studies on these have been carried out on people living at the borders of Thailand, Lao PDR, and Cambodia. This cross-sectional study was done in four areas along the borders of Thailand, Lao PDR, and Cambodia. Blood specimens were collected from subjects aged 15-18 years in four districts including Kantharalak, Si Sa Ket province (n = 36), Nam Khun (n = 109), Nam Yuen (n = 98), and Na Chaluai (n = 128), Ubon Ratchathani province, Thailand. RBC parameters were recorded, and serum ferritin (SF) level was measured. Diagnosis of thalassemia and hemoglobinopathies was based on hemoglobin (Hb) and DNA analyses. Measurement of C-reactive protein was performed to exclude false-negative result of iron deficiency. The prevalence of anemia was found to be 25.1%. ID accounted for only 10.5%. Various types of thalassemia were identified in 67.7% of the subjects. The overall prevalence of thalassemia included 3.5% α0-thalassemia, 0.8% β-thalassemia, 47.7% Hb E, and 53.6% α+-thalassemia. The proportions of ID, thalassemia and combined ID and thalassemia among anemic subjects were 6.5%, 66.6%, and 20.4%, respectively. The results indicate that thalassemia and hemoglobinopathies rather than ID are major causes of anemia in Thailand-Lao PDR-Cambodia triangle. This information should prove useful for implementing an anemia control program in the regions.


Bilateral Attenborough total knee replacement as a single procedure.
A series of 19 cases of simultaneous bilateral Attenborough Total Knee Replacement is presented. This semi-constrained prosthesis is ideal for this procedure as early mobilization is possible. In comparison to the available series of unilateral replacement, there has been no indication of an increase in any of the usual complications met in this type of surgery. This procedure is recommended for severe bilateral knee arthritis as it not only saves a second anaesthetic, but it helps rehabilitation and reduces the total hospital stay.


Simulating hydraulic interdependence between bridges along a river corridor under transient flood conditions.
Structural alterations to bridges may result in unintended consequences up- or downstream, such as changes in discharge, velocity, stream power, and water levels. This work presents a framework and methodology to analyze interconnected bridge-stream interactions under flood conditions. Such analysis may help prioritize limited resources available for bridge and river rehabilitations, facilitate holistic design of bridges and better-informed cost/benefit analyses, and address stakeholder concerns raised in response to planned bridge and infrastructure alterations. A two-dimensional unsteady HEC-RAS hydraulic model of the Otter Creek between Rutland and Middlebury, VT is used to simulate the impact of individual structures on the bridge-stream network, as well as potential sensitivity to those impacts, during extreme flood events. The presence of a bridge and approach roadway may induce measurable changes in peak discharge throughout the entire 46 miles of modeled river. These may be by as much as 10% at adjacent structures, down to 1% at structures as far as six miles upstream and nine miles downstream. Depending on their characteristics, bridges and roadways may either attenuate or amplify peak flood flows up- and downstream, or have little to no effect at all, suggesting that there is no easily predictable impact, and that hydraulic modeling is necessary for such analysis on rivers. Alterations to structures that develop substantial backwaters may result in the most dramatic impacts to the network, which can be both positive and negative. Affected bridges may or may not be sensitive to these changes in discharge; structures that do not experience relief (e.g., roadway overtopping) may be most sensitive to any distant perturbations.


'Brothers in arms': how men with cancer experience a sense of comradeship through group intervention which combines physical activity with information relay.
The study investigated how a group intervention programme (13 sessions over 16 weeks), designed for men with cancer (n = 17), affected their sense of well-being and had a positive impact on their ability to cope with the physical, psychological and social consequences of living with cancer. The close-knit relationships fostered between participants stimulated a sense of solidarity and commitment amongst them. New thinking in relation to gender, group dynamics and social processes is presented, as are the implications for clinical nursing practice in cancer care. The experience from male orientated group intervention programmes shows that men with cancer have undiscovered strengths, whilst some wish to die 'with their boots on'.


Variation in the density of oxytocin receptors in the brain as mechanism of adaptation to specific social and reproductive strategies.
Most species have predominant forms of social and reproductive behavior driven by many years of selection pressures and evolution. For example, rodent species can live in small or large groups, behave more tolerant or aggressively toward conspecifics (including newborns), and form or not bonds with other members of the group (including sexual partners). Any of those behavioral adaptations could result in good fitness for the species, but could also require compromises such as sharing resources, greater parental investment, increased risk of predation, etc. We propose that the oxytocin (OXT) system, among others neuroendocrine peptides, is at the basis of a neural mechanism that adapts and predisposes species to a particular social and reproductive form of living. In this review we will show evidence that the variability in the density of receptors for OXT (OXTR) in the nucleus accumbens (NAc) and the lateral septum (LS) predisposes species to adopt at least 4 different social and reproductive strategies in rodents. Large or medium size groups with lower conspecific spacing (preferred separation distance maintained by adult conspecifics), and high levels of promiscuity are characterized by low levels of OXTR in the NAc and LS (e.g. Ratus norvegicus, Ctenomys sociabilis, Scotinomys teguina, Cavia porcellus); small size groups with higher conspecific spacing and low levels of promiscuity are characterized by high OXTR in the NAc and the LS (e.g. Peromyscus californicus); large or medium groups with lower conspecific spacing and low levels of promiscuity characterized by high levels of OXTR in the NAc but low levels in the LS (e.g. Microtus ochrogaster, Heterocephalus glaber, Microtus kikuchii); and small or medium size groups with higher conspecific spacing and high levels of promiscuity characterized by low levels of OXTR in the NAc and high OXTR in the LS (e.g. Mus musculus, Ctenomys haigi, Peromyscus maniculatus, Microtus pennsylvanicus, Microtus montanus). Careful analysis of the distribution of OXTR, and other peptides receptors, in the brain can contribute to understand its function but also to predict reproductive and social strategies of species.


An overview of artificial intelligence techniques for diagnosis of Schizophrenia based on magnetic resonance imaging modalities: Methods, challenges, and future works.
Schizophrenia (SZ) is a mental disorder that typically emerges in late adolescence or early adulthood. It reduces the life expectancy of patients by 15 years. Abnormal behavior, perception of emotions, social relationships, and reality perception are among its most significant symptoms. Past studies have revealed that SZ affects the temporal and anterior lobes of hippocampus regions of the brain. Also, increased volume of cerebrospinal fluid (CSF) and decreased volume of white and gray matter can be observed due to this disease. Magnetic resonance imaging (MRI) is the popular neuroimaging technique used to explore structural/functional brain abnormalities in SZ disorder, owing to its high spatial resolution. Various artificial intelligence (AI) techniques have been employed with advanced image/signal processing methods to accurately diagnose SZ. This paper presents a comprehensive overview of studies conducted on the automated diagnosis of SZ using MRI modalities. First, an AI-based computer aided-diagnosis system (CADS) for SZ diagnosis and its relevant sections are presented. Then, this section introduces the most important conventional machine learning (ML) and deep learning (DL) techniques in the diagnosis of diagnosing SZ. A comprehensive comparison is also made between ML and DL studies in the discussion section. In the following, the most important challenges in diagnosing SZ are addressed. Future works in diagnosing SZ using AI techniques and MRI modalities are recommended in another section. Results, conclusion, and research findings are also presented at the end.


Peripheral nerve implant effects on survival of retinal ganglion layer cells after axotomy initiated by a penetrating lesion.
A lesion paradigm involving a small penetrating incision made through the sclera, choroid and retina of the adult rat eye creates a unique environment for the study of the damaged retina. More specifically, the dependable formation of a small focal retinal lesion makes this an ideal model for the determination of conditions that may stimulate retinal regeneration, wound repair and/or cell survival. Our previous studies have indicated that the placement of a desheathed peripheral nerve implant (PNI) into the lesioned adult rat eye: (1) initiated the rescue of retinal tissue that would normally die due to trauma; and (2) maintained the thickness and organization of most retinal layers adjacent to the lesion site, particularly the retinal ganglion cell layer (RGL). We report in the present work that a more detailed analysis of the RGL revealed a significant increase in the survival of axotomized neurons within this layer in the presence of a PNI over an 8-week post-implantation period. More specifically, there was a 60% loss of control RGL cells axotomized by the lesion 3 weeks previously in contrast to only a 30% loss in those tissues exposed to a PNI. Additional RGL cell size distribution studies point to the fact that the PNI appeared to affect the increased survival of cells greater than or equal to 70 micron2. Also the PNI effect demonstrated a specificity of response when tested against the influence of a tendon or suture implant.(ABSTRACT TRUNCATED AT 250 WORDS)


Simplified recombinational approach for influenza A virus reverse genetics.
Influenza A virus (FLUAV) reverse genetics requires the cloning of all eight viral genome segments into genomic expression plasmids using restriction enzyme cleavage and ligation. Herein is described the construction of a pair of plasmid vectors and their use in RecA Escherichia coli for direct recombination with influenza cDNA for reverse genetics. This approach is simpler; avoiding restriction digestion and ligation while maintaining the required orientation of genome segments. For this recombinational approach two plasmid constructs were generated, pHH21A and pHH21G, that both possess a 25 nucleotide recombination cassette comprised of the consensus 5' and 3' ends of the negative strand divided by a StuI cleavage site, but that differ at position 4 from the 3' end due to the presence of an A or G nucleotide (plus sense) to correspond to differences among genome segments. Using the described procedure it was possible to clone viral cDNA genomes of several avian and human FLUAVs into genomic expression plasmids in a single recombination step. This novel approach to generating sets of genomic plasmid constructs for reverse genetics reduces the time and complexity of procedures thus avoiding complications that would delay rescue of viral genomes for vaccine production or biological characterization and analysis.


Compliance of present recommendations of fatty acids in formulas for term infants with the actual human milk fatty acid composition in different populations.
Fats are the only dietary agents possibly modulating the individual membrane composition, which otherwise is "genetically" determined. In infancy, human milk represents the first natural source of fats. Although the fat intake of breastfed infants is quantitatively and qualitatively unique, it is not known to what extent their varying requirements are met by the fat composition in the milk of their mothers. The fat composition of arbitrarily chosen human milk is not always the best standard for that in infant formula.


Responsiveness and esteem support.
Esteem support refers to verbal and nonverbal aid provided to another individual to enhance how they feel about themselves and their attributes, abilities, and accomplishments. Esteem support is often exchanged in the context of close relationships (e.g., marriage, family, friendship), and may be a behavioral indicator of perceived partner responsiveness. Three theoretical models of esteem support offer guidance regarding associations between esteem support and perceived partner responsiveness: the optimal matching model of social support, the support gap model, and the cognitive-emotional theory of esteem support messages. We argue that effective esteem support is responsive, and that perceived partner responsiveness can foster an environment for exchanging esteem support in interpersonal relationships. These relationships should be examined explicitly in future research.


Botulinum toxin antibody type A titres after cessation of botulinum toxin therapy.
In some patients, therapy with botulinum toxin type A (BT-A) becomes ineffective due to formation of antibodies (BT-A-AB). The time course of BT-A-AB titres after cessation of BT-A therapy was quantitatively studied to determine whether and when they might drop. Thirteen patients (eight women, five men) with various dystonic syndromes and complete secondary therapy failure (CSTF) were included in this study (age at initiation of BT-A therapy, 48.2 +/- 11.3 years; number of injection series, 7.7 +/- 2.9; treatment time, 678.8 +/- 385.6 days; mean interinjection interval, 90.4 +/- 35.5 days; mean single dose, 546.7 +/- 336.9 EMU; cumulative dose, 4185.1 +/- 3375.7 EMU [1 EMU = 1 botox MU = 3 dysport MU]). During a monitoring period of at least 750 days after occurrence of CSTF, two or more BT-A-AB tests using the quantitative mouse diaphragm assay were performed. Eight of 13 BT-A-AB titres decreased. The onset of decrease could be detected after between approximately 500 and 1,750 days. After 1,250 to 2,250 days they had dropped below a level of 0.002 U/ml, where CSTF is unlikely. Five of 13 BT-A-AB titres did not decrease. For three of these five, the monitoring period was less than 1,500 days; a chance to drop remained. The other two were monitored for up to 2,400 days. Patients with decreasing and nondecreasing BT-A-AB titres did not exhibit statistically significant differences in either clinical characteristics or treatment parameters. When BT-A therapy was stopped the majority of BT-A-AB titres eventually decreased, allowing reinitiation of BT-A therapy. Application of new BT-A preparations with low antigenic potency might then become an interesting treatment option.


Measuring the outcome of clinical problem-solving.
The authors describe a new technique for measuring the outcomes of a clinical encounter using objective criteria derived from the performance of a criterion group.


Will treatment with digoxin antibody benefit pregnant patients with toxemia and elevated digoxin like factor?
Some pregnant patients with toxemia, especially those with thrombocytopenia, liver or renal dysfunction have elevated serum DLF (digoxin like factor). Since antidigoxin serum reduces the hypertension of DOCA hypertensive rats, it is proposed that antidigoxin antibodies be tried in the treatment of these select patients with toxemia of pregnancy.


Dietary and exercise practices of college-aged female bodybuilders.
The college-aged female bodybuilders in this study consumed nutrient-dense, low-fat foods and participated in strenuous exercise to develop their physiques. Non-competitors maintained consistent energy intake, exercise patterns, and body weight throughout the study period. In contrast, competitors exhibited periods of caloric restriction and excess associated with the pre- and post-competition events. This study indicates that college-aged female bodybuilders have food intake and exercise patterns that are unique to the sport.


Novel mechanisms of intracellular cholesterol transport: oxysterol-binding proteins and membrane contact sites.
Cholesterol is an essential membrane constituent, and also plays a key role in cell signalling. Within a cell, how cholesterol is transported and how its heterogeneous distribution is maintained are poorly understood. Recent advances have identified novel pathways and regulators of cholesterol trafficking. Sterol transfer by lipid-binding proteins, such as OSBP (oxysterol-binding protein), coupled with phosphatidylinositol 4-phosphate exchange at membrane contact sites (MCSs) has emerged as a new theme of cholesterol transport between organellar membranes. Moreover, a previously unappreciated role of peroxisomes in cholesterol trafficking has been revealed recently. These discoveries highlight the crucial role of MCSs, or junctions, in facilitating lipid movement, and provide mechanistic insights into how cholesterol is sorted in cells.


Effects of a cooling vest with sham condition on walking capacity in heat-sensitive people with Multiple Sclerosis.
Heat sensitivity is a common contraindication in people with Multiple Sclerosis (pwMS), and physical fatigue is one of the most frequently reported symptoms that can affect quality of life. Increases in body temperature may exacerbate fatigue and heat-related symptoms. Decreasing body temperature via cooling devices may mitigate disease symptoms and improve physical abilities and quality of life. This study evaluates the effects of a cooling vest with sham condition on walking capacity using a commercially-available cooling vest specifically designed for pwMS. A counter-balanced, cross-over design was used to assess the effects of a cooling vest (CryoVest Comfort, CryoInnov, France) (COLD) from a menthol-induced sham condition (CON) on ground walking time to exhaustion (Tex, s) and distance at exhaustion (Dex, m) in ambulatory pwMS. Secondary outcomes were heart rate (HR, bpm), thermal sensation (Tsens), skin chest (Tchest) and back (Tback) temperature. Ten females with Multiple Sclerosis (59 ± 9 years, EDSS 3.0-5.5) participated to the study. During COLD, pwMS walked significantly longer (1896 ± 602 vs. 1399 ± 404 s, p < 0.001) and farther (1879 ± 539 vs. 1302 ± 318 m, p < 0.001) than CON. Importantly, Tsens and HR at exhaustion were not significantly different between conditions, although Tchest (- 2.7 ± 1.8 °C, p < 0.01) and Tback (- 3.9 ± 1.8 °C, p < 0.001) were lower at volitional fatigue during COLD. The lightweight cooling vest improved total walking time and distance in heat-sensitive pwMS. These physiological improvements were likely due to feeling perceptually cooler in the COLD trial, compared to the corresponding point of fatigue in the CON condition.


Yeast ABC transporters in lipid trafficking.
Throughout its evolution, the ATP-binding cassette (ABC) transporter superfamily has experienced a rapid expansion in its substrate repertoire and functions. Of the diverse functions that these pumps offer, their drug transport properties have attracted considerable attention primarily owing to their clinical significance. Despite this fact, emerging evidence suggests that physiological substrates of transporters also affect the overall functioning of an organism. Lipids, as substrates of ABC transporters, constitute one feature found in all representative groups of the living kingdom. Due to the importance of lipid species in the cellular physiology of an organism, their proper distribution within cells is crucial. This fact is well exemplified by the vast number of medical conditions that have been caused as a result of perturbations in ABC transporter-mediated lipid transport in higher organisms. In yeasts, apart from providing transport functions, ABC transporters also coordinate regulatory networks with lipids. This review focuses on yeast ABC transporters involved in the transport of lipids and briefly discusses the integration of their regulatory network with that of the lipid species.


Complete Genome Sequences of Two Listeria Phages of the Genus Pecentumvirus.
Bacteriophages isolated from environmental sources can be used as a biocontrol against the foodborne pathogen Listeria monocytogenes Here, we present the complete genomes of LP-039 and LP-066, two Pecentumvirus bacteriophages that infect L. monocytogenes The genome sizes of LP-039 and LP-066 are 136.2 kb and 139.0 kb, respectively.


Etorphine and shuttle-box self-stimulation in the rat.
Rats were trained to turn rewarding electrical brain stimulation on and off by crossing back and forth in a shuttle-box. Moderate doses of the narcotic analgesic, etorphine, increased mean ON times while having little effect on OFF times. Tolerance did not develop to the reward enhancement action over five consecutive days of injections. This paradigm seems valuable for exploration of the reinforcing properties of narcotic drugs.


Reelin is overexpressed in the liver and plasma of bile duct ligated rats and its levels and glycosylation are altered in plasma of humans with cirrhosis.
Reelin is an extracellular matrix protein secreted by a variety of cell types in both embryonic and adult tissues, including the liver. However, the physiological significance of Reelin in normal and cirrhotic liver has thus far not been elucidated. We have investigated Reelin levels in the liver and plasma of bile duct ligated (BDL) rats. We observe a 115% increase in full-length Reelin and its 310- and 180-kDa fragments in liver extracts from BDL rats, compared to sham-operated controls (p = 0.005). The overall increase in protein levels was associated with a 30% increase of Reelin transcripts (p = 0.03). Immunohistochemical analysis demonstrated that hepatic stellate cells are the major source of Reelin in the injured liver. Increased liver Reelin in BDL rats leads to a pronounced 165% increase in the plasma levels (p < 0.001), particularly in the less abundant 180-kDa fragment (300% increase; p < 0.001). The data provides evidence that a fraction of plasma Reelin is synthesized in the liver. In human subjects suffering liver cirrhosis the level of the 180-kDa fragment was also increased by 140% in the plasma (p < 0.001). Analysis of Reelin glycosylation by lectin binding demonstrated that the 180- and predominant 310-kDa Reelin fragments in the plasma of cirrhotic patients are differentially glycosylated compared to non-diseased control subjects. The data show that Reelin is up-regulated in experimental liver cirrhosis and that its levels and glycosylation are altered in plasma from patients with cirrhosis, thereby supporting that Reelin is involved in the pathogenesis of liver disease.


Recurrent peripheral odontogenic keratocyst: Review of the literature and presentation of a novel case initially masquerading as an atypical infected lateral periodontal cyst.
To review published cases and case series of the peripheral odontogenic keratocyst (POKC) of the gingiva, report an unusual presentation, and discuss lesional recurrence. A search of the English language literature for gingival OKCs was conducted. The inclusion of new case yielded a database containing 29 affected patients. Clinical, surgical, radiographic, and histopathologic findings have been summarized. With available patient demographics, 62.5% were female and 37.5% were male, with an overall mean age at diagnosis of 53.8 years. There was near-equal lesional affinity for the jaws, of which 44.0% occurred in the posterior region, 32.0% anteriorly, and 24.0% overlapped these areas. Twenty-five percent of lesions had a normal color, 30.0% appeared yellow, 20.0% were white, and 10.0% were blue. The majority of lesions were < 1 cm and nearly 42% manifested exudation or fluctuance. Lesional pain was infrequent. Pressure resorption was recorded in 45.8% of cases. Most lesions were managed with conservative surgical modalities. Follow-up information was available in 16 primary cases, of which 5 recurred, signifying a 31.3% recurrence rate, including the featured case, which recurred twice. To reduce recurrence of a gingival OKC, supraperiosteal dissection is advocated. Further, it is advised to follow POKCs for 5-7 years postoperatively, remaining vigilant for subtle clinical manifestations of recurrence. Timely discovery and excision of a POKC of the gingiva may decrease the incidence of a mucogingival defect.


Patterns of Women's Postpartum Weight Retention and Its Associations with Maternal Obesity-Related Factors and Parity.
There is not much data on the effects of the timing of gestational weight gain (GWG), pre-pregnancy waist circumference (WC), pre-pregnancy body mass index (BMI), and parity, with postpartum weight retention (PPWR) trajectories. This study was based on a longitudinal cohort. Latent growth mixture models were applied to identify the latent trajectories of PPWR and test the effects of the predictors on distinct classes of PPWR trajectories. Three PPWR trajectories were identified. About 2.8% (n = 26) of women were classified into Class 1, with an inverted U-shape trajectory; 6.6% (n = 61) were assigned to Class 2, with a rapid increase trajectory; 90.6% (n = 837) were classified into Class 3, with a significant decrease. Women who had a lower pre-pregnancy BMI (β = -0.279), higher pre-pregnancy WC (β = 0.111) and GWG (β = 0.723) were at a higher risk of retaining more weight at 1 month postpartum. Only GWG, especially GWG during late pregnancy, was associated with the rate of PPWR change. Parity was not associated with the changes in PPWR, while, compared to Class 1 trajectory, multiparous women were protected from having a Class 2 trajectory. Early targeted interventions should be taken to prevent women who were primiparous, and/or had a lower pre-pregnancy BMI and higher pre-pregnancy WC and GWG, from excessive PPWR.


Mnemonics for DSM-IV substance-related disorders.
A series of acronyms was developed to assist in recalling the DSM-IV diagnostic criteria for substance-related disorders. In order to facilitate recall, most of the mnemonics are related in some way to the disorder itself. In general, each letter of the acronym relates to an element of the diagnostic criteria. These mnemonics are intended to be helpful in a variety of academic and medical settings.


Acidic protease from human seminal plasma. Purification and some properties of active enzyme and of proenzyme.
A procedure to purify to homogeneity the active form as well as the proenzyme form of the acidic protease of human seminal plasma is described. This involved precipitation with ammonium sulfate, chromatography on diethylaminoethylcellulose, Sephadex G-200, and Sephadex G-100. The molecular weights of the active form and of the proenzyme were determined by electrophoresis and gel filtration to be 35,000 and 42,000, respectively. The proenzyme was more stable than the active form in alkaline solution and can be converted into the active enzyme under acidic conditions. The active form of the acidic protease can hydrolyze hemoglobin, N,N'-dimethylcasein, N-acetyl-L-phenylalanyl-L-diiodotyrosine, and N-benzyloxycarbonyl-L-glutamyl-L-phenylalanine, but cannot hydrolyze bovine serum albumin, ovalbumin, N-benzyloxycarbonyl-L-glutamyl-L-tyrosine. The active form was also inhibited by p-bromophenacyl bromide and 1,2-epoxy-3-(p-nitrophenoxy)propane.


Golf club related basal skull fracture: a case study.
Basal skull fractures, although rare, do occur and a high index of suspicion for high velocity injuries, should be at the forefront of the clinicians mind, particularly those from a golf club. Head injury in children is a common presentation to any Paediatric Emergency Department. With effective examination skills, recognition of signs of basal skull fracture such as haemotympanum, even in the absence of altered neurological findings, ensures safe and effective practice enabling correct and justifiable clinical decisions to be made. This is vital to ensure not only the correct investigative procedure is requested and performed, but also on discussion with the appropriate specialists, the correct treatment is also prescribed. This case study examines the use of computed tomography in the diagnosis of basal skull fractures and highlights further discussion into the appropriate treatment of children diagnosed with basal skull fractures.


Long-term durability of alumina ceramic heads in THA.
The optimal type of bearing for hip arthroplasty remains a matter of debate. Ceramic-on-polyethylene (CoP) bearings are frequently used in younger and more active patients to reduce wear and increase biocompatibility compared to Metal-on-Polyethylene (MoP) bearings. However, in comparison to metal heads, the fracture risk of ceramic heads is higher. In addition, ceramic head fractures pose a serious complication which often necessitates major revision surgery. To date, there are no long-term data (>20 years of follow-up) reporting fracture rates of the ceramic femoral heads in CoP bearings. The purpose of this research was to investigate long-term CoP fracture rate. We evaluated the clinical and radiographic results of 348 cementless THAs treated with 2nd generation Biolox Al₂O₃ Ceramic-on-Polyethylene (CoP) bearings consecutively implanted between January 1985 and December 1989. The mean age at implantation was 57 years. The patients were followed for a minimum of 20 years. At the final 111 had died, and 5 were lost to follow-up. The cumulative incidence of ceramic head fractures in the long-term was estimated using a competing risk analysis. The cumulative incidence of ceramic head fracture after 22-years was estimated with a competing risk analysis at 0.29% after 22-years (SE = 2.09%; 95% - CI: 0.03-1.5%). The radiographic analysis revealed no impending failures at final follow-up. The fracture rate of second-generation ceramic heads using a CoP articulation remains very low into the third decade after cementless THA.


Altering the therapeutic paradigm towards a distal bowel margin of < 1 cm in patients with low-lying rectal cancer: a systematic review and commentary.
The 1-cm rule of distal bowel clearance in patients with low-lying rectal cancer undergoing anterior resection is based mainly on pathological data showing distal intramural spread. Because clinical data are contradictory, a review that includes only cancers located ≤ 5 or ≤ 6 cm from the anal verge was carried out. A systematic review of the literature identified seven studies that presented results in relation to a margin of ≤ 1 cm (n = 293) vs > 1 cm (n = 315). In six studies, pre- or postoperative radiotherapy was implemented, and in one study patients were treated with surgery alone. Three studies, all implementing radiotherapy, reported results related to a margin of ≤ 5 mm (n = 51) vs > 5 mm (n = 125). In none of the studies were the differences in local recurrence rate between the small and large margin groups statistically significant. The pooled analysis of six studies, in which patients received perioperative radiotherapy, showed a 1.2% [95% confidence interval (Cl) -4.5-7.0%] higher local recurrence rate in the ≤ 1 cm margin group compared with the > 1 cm margin group (P = 0.6). The corresponding figures for the ≤ 5 mm cut-off point were 0.5% (95% CI -7.6-8.7%, P = 0.9). The 5-year local recurrence rate in the only study in which radiotherapy had not been used was 8.6% higher in the ≤ 1 cm margin group compared with the > 1 cm margin group (P = 0.09). Clinical evidence does not support the 1-cm rule in patients with low-lying rectal cancer undergoing pre- or postoperative radiotherapy.


Bilateral chondroma of the auricle.
Benign extraosseous cartilaginous lesions are uncommon and favor mainly the soft tissues of the hands and feet. We report a case of chondroma of both auricles. This localization has not been previously reported in the literature.


Biodirected mutagenic chemical assay of PM(10) extractable organic matter in Southwest Mexico City.
The concentration of breathable particles (PM(10)) in urban areas has been associated with increases in morbidity and mortality of the exposed populations, therein the importance of this study. Organic compounds adsorbed to PM(10) are related to the increased risk to human health. Although some studies have shown the lack of correlation between specific mutagenic compounds in an organic complex mixture (OCM) and the mutagenic response in several bioassays, the same organic compounds selectively separated in less complex groups can show higher or lower mutagenic responses than in the OCM. In this study, we fractionated the OCM, from the PM(10) in four organic fractions of increasing polarity (F1-F4). The Salmonella bioassay with plate incorporation was applied for each one using TA98, with and without S9 (mammalian metabolic activation), and YG1021 (without S9) strains. The most polar fraction (F4) contained the greatest mass followed by F1 (non-polar), F2 and F3 (moderately polar). The concentrations of the OCM as well as the F4 were the only variables correlated with PM(10), atmospheric thermal inversions, fire-prone area, NO(2), SO(2), CO, rain and relative humidity. This indicated that polar organic compounds were originated in gas precursors formed during the atmospheric thermal inversions as well as the product of the incomplete combustion of vehicular exhausts and of burned vegetation. The percentages of the total PAH, and the individual PAH with molecular weight > or = 228 g mol(-1) (except retene) correlated with the percentages of indirect-acting mutagenicity in TA98+S9. The percentages of the total nitro-PAH and most of the analyzed individual nitro-PAH correlated with percentages of the direct-acting mutagenicity in both TA98-S9 and YG1021, the latter being more sensitive. In general, the highest mutagenic activity (indirect and direct) was found in F3 (moderately polar) and in F4 (polar). The non-polar fraction (F1) did not exhibit any kind of mutagenicity. In 77% of the cases, mutagenic activity was higher in the sum fractions with respect to their OCM. The combinations between F1, F2 and F4, with F3 under different or equal proportions suggested that mutagenicity reduction, in the combined matter of January (with TA98+S9 and YG1021) and of May (with YG1021), was due to concentrations of mutagens and non-mutagens in each fraction, and not to an antimutagenic effect. The organic compounds present in the non-polar fractions showed no antagonism, inhibition or reduction in the most mutagenic fractions in both indirect- and direct-acting mutagenicity, and the less polar organic compounds in F3 reduced mutagenicity in F4, in both months.


Percutaneous access for endovascular abdominal aortic aneurysm repair: can selection criteria be expanded?
Previous reports suggest that percutaneous access for endovascular abdominal aortic aneurysm repair (P-EVAR) is as safe as open access (O-EVAR) in patients with favorable femoral anatomy. Severe femoral artery calcification and obesity have been considered relative contraindications to P-EVAR, but these criteria have not been evaluated. The purpose of this study was to assess the postoperative anatomic changes associated with P-EVAR versus O-EVAR using three-dimensional (3-D) computed tomographic (CT) reconstruction and to evaluate the overall results of the two procedures in a group of patients with suboptimal femoral anatomy. During a recent 26-month period, 173 patients underwent EVAR at our institutions, including 35 P-EVARs. Of these, 22 (63%) had complete pre- and postoperative CT imaging of the femoral arteries. These subjects were compared to 22 matched controls who underwent O-EVAR during the same period. Automated 3-D reconstructions were used to measure the following anatomic femoral artery parameters before and after EVAR: arterial depth, calcification score, minimum diameter and area, and maximum diameter and area. Of the 88 study arteries, 50 underwent open access and 38 percutaneous access (Proglide, n=11; Prostar XL, n=27). Both groups were similar regarding sheath size, number of components, operative time, blood loss, and length of stay. Significantly more O-EVAR subjects suffered groin complications (p=0.02), including five hematomas, two wound infections, two femoral thromboses, and one vessel which required patch repair. In the P-EVAR group there was only one hematoma, which was managed conservatively. There was no difference between the P-EVAR and O-EVAR groups with respect to femoral artery calcification (Agatston scores 667+/-719 vs. 945+/-1,248, p=0.37). Obesity (body mass index >30) was documented in six (27%) of both the P-EVAR and O-EVAR groups (p=nonsignificant). Pre- and postoperative CT-derived anatomic data showed a significant decrease in the minimal vessel area with O-EVAR compared to P-EVAR (p=0.02). This study demonstrates that patients with obesity or severely calcified femoral arteries can be successfully treated percutaneously with fewer minor groin complications.


Automatically detecting Crohn's disease and Ulcerative Colitis from endoscopic imaging.
The SI-CURA project (Soluzioni Innovative per la gestione del paziente e il follow up terapeutico della Colite UlceRosA) is an Italian initiative aimed at the development of artificial intelligence solutions to discriminate pathologies of different nature, including inflammatory bowel disease (IBD), namely Ulcerative Colitis (UC) and Crohn's disease (CD), based on endoscopic imaging of patients (P) and healthy controls (N). In this study we develop a deep learning (DL) prototype to identify disease patterns through three binary classification tasks, namely (1) discriminating positive (pathological) samples from negative (healthy) samples (P vs N); (2) discrimination between Ulcerative Colitis and Crohn's Disease samples (UC vs CD) and, (3) discrimination between Ulcerative Colitis and negative (healthy) samples (UC vs N). The model derived from our approach achieves a high performance of Matthews correlation coefficient (MCC) > 0.9 on the test set for P versus N and UC versus N, and MCC > 0.6 on the test set for UC versus CD. Our DL model effectively discriminates between pathological and negative samples, as well as between IBD subgroups, providing further evidence of its potential as a decision support tool for endoscopy-based diagnosis.


Plasma fluorescein and fluorescein glucuronide in patients with selected eye diseases.
Systemically administered fluorescein (F) is rapidly transformed to the fluorescent metabolite fluorescein glucuronide (FG). Little is known about how diseases can influence the synthesis or disposition of FG. We studied F and FG in the plasma ultrafiltrate of 75 people who were normal or had diabetes, retinitis pigmentosa, or idiopathic rhegmatogenous retinal detachment. F and FG were determined by high-performance liquid chromatography. The concentration of FG was comparable to F 1 h after an intravenous injection of F, both in normal subjects and in patients with retinitis pigmentosa, which suggests that FG may not be an important contributor to the vitreous fluorescence at that time. At later times FG substantially exceeded F. The concentration of FG was significantly higher in diabetics than in the other groups 14 h after an oral dose of F. Accordingly, the possible effect of disease on plasma dye concentrations should be considered in studies measuring F by fluorescence hours after systemic F administration, since this could influence the intraocular fluorescence irrespective of any alteration in ocular function.


Configurations of the driving factors promoting China's commercial health insurance: A comparative qualitative analysis based on the technology-organization-environment framework.
With the nation's remarkable improvement in living standards, China's health insurance system cannot satisfy people's higher demands; therefore, it is necessary to promote the supply of commercial health insurance (CHI) in China. Based on the technology-organization-environment (TOE) framework, this study constructs a novel analysis framework to investigate the driving path of China's CHI. Employing the data of 31 provincial regions of China in 2018, a fuzzy-set qualitative comparative analysis is conducted to analyze configurations. We also adopt a necessary condition analysis in the robustness check to examine the necessary conditions, determining that no necessary relationship exists between possible conditions and the performance of CHI. More particularly, three sufficient configurations, TOE strategy, government attention (GA)-environment adaptability (EA)-citizen demand (CD) strategy, and dual EA-CD strategy are demonstrated to achieve high performance, and the other three configurations of technological management capability (TMC)-EA-CD strategy, technological infrastructure (TI)-EA strategy, and combined TI-TMC-EA strategy do not result in high performance. In addition, technological conditions (TI and TMC) and EA are relatively more important than the other configurations. Notably, government departments' financial expenditure is found to have a negative effect on CHI promotion.


Evaluation of synthetic serum substitute versus serum as protein supplementation for mouse and human embryo culture.
Our purpose was to determine the effect of Synthetic Serum Substitute (SSS) versus serum supplementation on fertilization rates and subsequent development of embryos from patients undergoing IVF. Experiment I compared the effects of SSS to human serum on mouse embryo development. Two hundred one-cell B6D2F1 mouse embryos were cultured in 100-microliter droplets of human tubal fluid (HTF) containing either (1) no protein (control; n = 37), (2) 15% serum from women with tubal infertility (n = 44), (3) 15% serum from women with endometriosis (n = 49), (4) 15% fertile donor serum (n = 33), or (5) 15% SSS (n = 37). Experiment II compared the effects of SSS to human serum on the development of embryos from patients undergoing IVF. Thirty-three women were included in this study. A total of 371 oocytes was cultured in HTF containing either (1) maternal or donor serum (n = 140) or (2) 15% SSS (n = 231). Embryo development was evaluated 48 hr after fertilization. In Experiment I, the rate of blastocyst development was evaluated at 48, 72, and 96 hr of culture. Sixty-four and nine-tenths percent of embryos cultured in SSS were morulae at 48 hr of culture (versus 5.4, 0, 8.2, and 6.1 in Groups 1, 2, 3, and 4, respectively). By 72 hr, 29.7% of these embryos had developed into blastocysts (versus 0, 0, 8.2, and 3.0, for Groups 1, 2, 3, and 4, respectively). This percentage increased to a total of 83.7 after 96 hr (versus 27.0, 20.4, 38.8, and 39.4 for Groups 1, 2, 3, and 4, respectively). Forty-three and two-tenths percent of the blastocysts cultured in SSS had hatched from their zonae by 96 hr. With the exception of Group 5, which had a rate of 9.1%, embryo hatching was not observed in any of the groups at the termination of culture (96 hr). In Experiment II there were no differences in cell stage or quality of human embryos cultured in SSS or serum, but fertilization rates tended to be better (P = 0.07) for oocytes inseminated in media containing SSS (70.0%, vs 55.0% for serum). SSS appears to be a superior protein source for mouse embryo growth and is as good as serum from fertile donors in promoting in vitro human embryo development.


Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E2 results in high interleukin-12 production and cell migration.
Dendritic cells (DC) are professional antigen-presenting cells of the immune system that play a key role in regulating T cell-based immunity. In vivo, the capacity of DC to activate T cells depends on their ability to migrate to the T cell areas of lymph nodes as well as on their maturation state. Depending on their cytokine-secreting profile, DC are able to skew the immune response in a specific direction. In particular, IL-12p70 producing DC drive T cells towards a T helper 1 type response. A serious disadvantage of current clinical grade ex vivo generated monocyte-derived DC is the poor IL-12p70 production. We have investigated the effects of Toll-like receptor (TLR)-mediated maturation on ex vivo generated human monocyte-derived DC. We demonstrate that in contrast to cytokine-matured DC, DC matured with poly(I:C) (TLR3 ligand) and/or R848 (TLR7/8 ligand) are able to produce vast amounts of IL-12p70, but exhibit a reduced migratory capacity. The addition of prostaglandin E2 (PGE2) improved the migratory capacity of TLR-ligand matured DC while maintaining their IL-12p70 production upon T cell encounter. We propose a novel clinical grade maturation protocol in which TLR ligands poly(I:C) and R848 are combined with PGE2 to generate DC with both high migratory capacity and IL-12p70 production upon T cell encounter.


Screening for gynaecologic cancers in genetically predisposed women.
Hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colon cancer syndrome are the two most important syndromes responsible for inherited cancers in gynaecology. Genetic testing is available for both these syndromes. Breast cancer gene testing is affordable and easy in women with ancestry where the mutation patterns are known, whereas other population groups need full gene screening. Hereditary non-polyposis colon cancer syndrome can now be diagnosed more frequently with the use of immunohistochemistry. Ovarian cancer risk is high in hereditary breast and ovarian cancer syndromes, and advanced screening techniques should be used when preventive surgery is not an option. Early detection techniques offer less protection than prophylactic removal, but enable women to retain their reproductive organs. Oophorectomy has the advantage of reducing breast cancer risk. In colorectal cancer syndromes, the risk for endometrial and ovarian cancer is much elevated. These risks should be recognised and addressed as these diseases are easy to prevent.


MyCare study: protocol for a controlled trial evaluating the effect of a community-based intervention on psychosocial, clinical outcomes and hospital admission rates for adults with severe mental illness.
People with serious mental illness (SMI) often fail to receive adequate treatment. To provide a higher level of support, mental health systems have been reformed substantially to integrate mental healthcare into the community. MyCare is one such community-based mental health model of care. This paper describes the study protocol of a controlled trial examining the effect of MyCare on psychosocial and clinical outcomes and hospital admission and duration rates for adults with SMI. This is a multisite non-randomised controlled trial with a 3, 6 and 12-month follow-up period. The study participants will be adults (18-64 years of age) with SMI recruited from Hobart, Launceston and the North-West of Tasmania. The treatment group will include adults who receive both the MyCare intervention and standard mental health support; the control group will include adults who receive only standard mental health support. The primary outcome includes psychosocial and clinical functioning and the secondary outcome will examine hospital admission rates and duration of stay. Mixed-effects models will be used to examine outcome improvements between intake and follow-up. This trial will generate the evidence needed to evaluate the effect of a community mental health support programme delivered in Tasmania, Australia. If MyCare results in sustained positive outcomes for adults with SMI, it could potentially be scaled up more broadly across Australia, addressing the inequity and lack of comprehensive treatment that many individuals with SMI experience. This study has been approved by the Tasmanian Health and Medical Human Research Ethics Committee. The findings will be disseminated to participants and staff who delivered the intervention, submitted for publication in a peer-reviewed journal and shared at academic conferences. ACTRN12620000673943.


Chondrogenesis from umbilical cord blood cells stimulated with BMP-2 and BMP-6.
Umbilical cord blood contains undifferentiated mesenchymal stem cells (MSCs) with chondrogenic potential that may be used for the repair of joint damage. The role of growth factors during the process of chondrogenesis is still not entirely understood. The objective of this study was to evaluate the formation of chondrocytes, cartilaginous matrix and type II collagen from human umbilical cord blood stem cells exposed to two different growth factors, BMP-6 and BMP-2, while being cultured as a micromass or a monolayer. Umbilical cord blood was obtained from full-term deliveries, and then, mononuclear cells were separated and cultured for expansion. Afterward, these cells were evaluated by flow cytometry using antibodies specific for MSCs and induced to chondrogenic differentiation in micromass and monolayer cultures supplemented with BMP-2 and BMP-6. Cellular phenotype was evaluated after 7, 14 and 21 days by RT-PCR and Western blot analysis to identify the type II collagen and aggrecan. The expanded cells displayed surface antigens characteristic of mesenchymal progenitor cells and were negative for hematopoietic differentiation antigens. Type II collagen and aggrecan mRNAs were expressed from day 14 in cells stimulated with BMP-2 or BMP-6. Type II collagen was demonstrated by Western blotting in both groups, and the greatest expression was observed 21 days after the cells were stimulated with BMP-2 cultured in micromass. BMP-2 in micromass culture was more efficient to induce the chondrogenesis.


Single-cell transcriptomics reveals maturation of transplanted stem cell-derived retinal pigment epithelial cells toward native state.
Transplantation of stem cell-derived retinal pigment epithelial (RPE) cells is considered a viable therapeutic option for age-related macular degeneration (AMD). Several landmark Phase I/II clinical trials have demonstrated safety and tolerability of RPE transplants in AMD patients, albeit with limited efficacy. Currently, there is limited understanding of how the recipient retina regulates the survival, maturation, and fate specification of transplanted RPE cells. To address this, we transplanted stem cell-derived RPE into the subretinal space of immunocompetent rabbits for 1 mo and conducted single-cell RNA sequencing analyses on the explanted RPE monolayers, compared to their age-matched in vitro counterparts. We observed an unequivocal retention of RPE identity, and a trajectory-inferred survival of all in vitro RPE populations after transplantation. Furthermore, there was a unidirectional maturation toward the native adult human RPE state in all transplanted RPE, regardless of stem cell resource. Gene regulatory network analysis suggests that tripartite transcription factors (FOS, JUND, and MAFF) may be specifically activated in posttransplanted RPE cells, to regulate canonical RPE signature gene expression crucial for supporting host photoreceptor function, and to regulate prosurvival genes required for transplanted RPE's adaptation to the host subretinal microenvironment. These findings shed insights into the transcriptional landscape of RPE cells after subretinal transplantation, with important implications for cell-based therapy for AMD.


A computerized integrated system for the assessment of central and peripheral chemoreflex sensitivity.
The assessment of chemoreflex sensitivity (CRS) is of major importance in studies investigating the adaptation of ventilation to the needs of human body. Increased sensitivity of chemoreceptors to both hypoxia and hypercapnia has recently been shown to be a powerful and independent prognosticator in heart failure (HF) patients, thus highlighting the importance of the assessment of CRS also in the clinical setting. In spite of this, the measurement of CRS is currently limited to the research setting. One possible reason might be the lack of suitable commercial equipments. On the basis of these considerations, we designed a system to carry out a comprehensive assessment of CRS, including both central and peripheral chemoreceptors. The system is based on the integration of different commercial devices and is entirely managed by a custom software written in Matlab language. The main features of our system are: (1) the implementation of standard methods (the Read's rebreathing test, the CO2 single breath test and the transient hypoxia test) suitable for both pathological and healthy subjects, (2) data quality assurance and reduction of subjective judgment in the analysis through advanced analysis procedures and statistical outliers rejection, and (3) full interactive control of every step of the recording and analysis procedures. The system is currently used in our Institution in the assessment of CRS in HF patients, chronic obstructive pulmonary disease patients and healthy subjects. It has proven to be very effective and easy to use even by clinical personnel without a specific background in respiratory function assessment.


Phase separation of a protein-water mixture in cold cataract in the young rat lens.
A remarkable resemblance between the appearance of opacity in lysozyme--salt water mixtures and the development of opacity in cold cataract in the young rat lens is strong evidence that cold cataract is fundamentally a phase separation of the "protein-water binary mixture" in the lens.