Chronic bovine fasciolosis associated cholangiolithiasis: a case report.
Cholangiolithiasis is a rare condition in animals wherein the choleliths are formed in the biliary tracts causing chronic inflammation. In the current study, choleliths which were firm and friable concretions of approximately 3-4 cm in diameter were found in the bile ducts of the liver of an adult cattle infected with Fasciola gigantica. Two such irregularly shaped concretions were encountered in the two biliary tracts leading to common bile duct in the liver. There were localized irregular saccular dilatation and numerous liver flukes in the bile ducts. Further, several small hard concretions of varying sizes were also present in the ducts. The histological investigation revealed chronic cholangitis with bile duct hyperplasia and cirrhosis. The co-existence of F. gigantica and choleliths indicated the physical pre-disposition for the formation of bile concretions in the bile duct which is not a common site for the occurrence of gall stones.


The economics of treating chronic hepatitis C patients with peginterferon alpha-2a (40 kDa) plus ribavirin presenting with persistently normal aminotransferase.
Peginterferon alpha-2a (40 kDa) plus ribavirin is effective at achieving sustained viral response compared with no treatment in patients with chronic hepatitis C (CHC) and persistently normal aminotransferase levels (PNALT). The cost-effectiveness of treating CHC in the setting of PNALT has not been assessed. Disease progression in patients with PNALT was simulated in a Markov model. The rate of fibrosis progression, quality of life and costs for each health state were based on literature estimates. The perspective of the Italian National Health Service was adopted and costs (euro 2003) and benefits were discounted at 3%. Sensitivity analyses were performed on important parameters. The primary analysis compared combination therapy with peginterferon alpha-2a (40 kDa) plus ribavirin to no treatment in a cohort of patients with mean age 45 years, and was based on findings from a multinational, randomized trial in patients with PNALT. In genotype 1 patients, the risk of cirrhosis at 30 years is forecast to fall from 32% with no treatment to 19% with combination therapy, increasing quality-adjusted life years (QALYs) by 0.74 years at an incremental cost per QALY gained of euro 16,831. The 30-year risk of cirrhosis in genotype 2 or 3 is projected to fall to 9% with combination therapy, an increase in QALYs of 1.34 years, at an incremental cost per QALY gained of euro 3,000. Thus treatment of PNALT with peginterferon alpha-2a (40 kDa) plus ribavirin is projected to reduce the incidence of cirrhosis, increase life expectancy and have an acceptable cost-effectiveness ratio from a societal perspective.


Evaluation of calcium depletion as a strategy for enhancement of mucosal absorption of macromolecules.
Extracellular calcium is crucial for functioning of the epithelial barrier. Compounds that bind calcium, reducing its extracellular levels, have therefore been investigated as mucosal absorption enhancers. However, the conditions under which calcium reduction sufficiently modulates the epithelial barrier to result in meaningful improvements in mucosal drug absorption are unclear. Present work investigated the settings in which calcium depletion leads to optimal epithelial barrier-modulating effects. Using Calu-3 and Caco-2 cell layers and inducing calcium depletion site-specifically (apically, basolaterally or on both sides) we demonstrate that apical calcium removal produces a modest effect on the tight junctions (the extent of the effect being dependent on the duration of apical calcium unavailability), whilst basolateral calcium exhaustion leads to a prominent effect on the epithelial barrier. However, using polyacrylic acid as an example, we show that polymeric calcium-binding agents proposed as mucosal absorption-enhancing excipients alter calcium levels exclusively on the apical side of the epithelium, which explains their modest effect on epithelial barrier modulation (also demonstrated in our work). Therefore the use of calcium-depleting agents, especially those based on macromolecular polymers, is a relatively inefficacious strategy to promote mucosal absorption of macromolecules.


Dual-domain cascade of U-nets for multi-channel magnetic resonance image reconstruction.
The U-net is a deep-learning network model that has been used to solve a number of inverse problems. In this work, the concatenation of two-element U-nets, termed the W-net, operating in k-space (K) and image (I) domains, were evaluated for multi-channel magnetic resonance (MR) image reconstruction. The two-element network combinations were evaluated for the four possible image-k-space domain configurations: a) W-net II, b) W-net KK, c) W-net IK, and d) W-net KI. Selected four element (WW-nets) and six element (WWW-nets) networks were also examined. Two configurations of each network were compared: 1) each coil channel was processed independently, and 2) all channels were processed simultaneously. One hundred and eleven volumetric, T1-weighted, 12-channel coil k-space datasets were used in the experiments. Normalized root mean squared error, peak signal-to-noise ratio and visual information fidelity were used to assess the reconstructed images against the fully sampled reference images. Our results indicated that networks that operate solely in the image domain were better when independently processing individual channels of multi-channel data. Dual-domain methods were better when simultaneously reconstructing all channels of multi-channel data. In addition, the best cascade of U-nets performed better (p < 0.01) than the previously published, state-of-the-art Deep Cascade and Hybrid Cascade models in three out of four experiments.


pH regulates peptide-receptor perception.
Diverse plant small peptides are perceived by their corresponding receptors to mediate local or long-distance intercellular communications in various developmental and adaptive programs; notably, the mechanisms of peptide-receptor perception remain largely unrevealed. Two reports (Liu et al.; Diaz-Ardila et al.) shed light on how pH regulates peptide-receptor perception.


Potential role of active decompression and distraction sugosteogenesis for the management of ameloblastomas: Report of two cases and review of the literature.
Ameloblastomas are aggressive odontogenic entities well-known for their high tendency to recur. Clinical presentation includes lesions discovered on routine examination or radiographs, pathologies causing facial swelling, pain, cortical expansion, tooth mobility, root resorption, and paresthesia. Radiographic findings comprise large unilocular or multilocular radiolucencies with well-defined borders associated to an impacted tooth. Ameloblastomas are classified as unicystic, multicystic/solid, and peripheral. Treatment options include marsupialization, decompression, enucleation, or curettage with or without adjuvant measures such as Carnoy's solution, marginal resection, and segmental resection. Recently, active decompression with distraction sugosteogenesis (ADDS) was introduced for the conservative management of odontogenic cystic conditions. The purpose of this paper is to present 2 cases of a conventional ameloblastoma treated by means of ADDS. The purpose of this novel approach is to significantly reduce the amount of time required to decompress cystic-like lesions. In these cases, ADDS proved to be a viable treatment because it demonstrated a reduction in size of the initial lesion by new osseous formation within 2 weeks of placement of the device. The cases presented in this paper demonstrate that ADDS could be a valuable treatment modality for this type of ameloblastoma, although further research is necessary to validate this philosophy.


China green credit policy and corporate green technology innovation: from the perspective of performance gap.
Green credit policy is an essential external driver of green transformation for companies, while the performance gap is a vital decision-making foundation for innovative reform for managers. Both work together and influence corporate green technology innovation. Based on this, this research examines the influence of green credit on corporate green technology innovation under the assumptions of "cost compliance" and "innovation compensation" from the perspective of the performance gap. It shows that green credit policy inhibits green technology innovation among heavy polluting firms. Still, after considering the performance gap, the inhibiting effects are only found in firms with performance deficits. In contrast, green credit policy promotes green technology innovation when firms have a performance surplus. The heterogeneity analysis finds that the boosting effect of performance surplus is more significant in non-state, large-scale, and financially developed regions.


Scintigraphic evaluation of regression of abnormal Q waves in myocardial infarction.
We report regression of the abnormal Q waves of an inferior old myocardial infarction after an additional anterior acute myocardial infarction, and demonstrate the scintigraphic correlation and chronological course of this phenomenon. Scintigraphic findings in the present case here may contribute to an interpretation of regression of abnormal Q waves in myocardial infarction.


Gender differences in perceived environmental correlates of physical activity.
Limited research has been conducted on gender differences in perceived environmental correlates of physical activity (PA). The purpose of this study was to explore the potential role of gender in the link between perceived environment and PA. Using a telephone-administered survey, data was collected on leisure time physical activity (LTPA), perceptions of the neighbourhood environment, and self-efficacy in a representative sample of 1209 adults from the province of Alberta, Canada. LTPA was regressed on ten measures of perceived neighbourhood environment and self-efficacy in a series of logistic regressions. Women were more likely than men to perceive their neighbourhood as unsafe to go for walks at night (chi2 = 67.46, p < 0.001) and to report seeing people being active in their neighbourhood (chi2 = 6.73, p < 0.01). Conversely, women were less likely to perceive easy access to places for PA (chi2 = 11.50, p < 0.01) and availability of places to buy things within easy walking distance from home (chi2 = 4.30, p < 0.05). Adjusting for age, education, income, and place of residence, access to places for PA (OR = 2.49) and interesting things to look at in the neighbourhood (OR = 1.94), were associated with higher levels of LTPA in men. Access to places for PA (OR = 2.63) and reporting seeing people being active (OR = 1.50) were associated with increased LTPA among women. After controlling for sociodemographic variables and self-efficacy, the presence of shops and places to buy things within easy walking distance from home (OR = 1.73), interesting things to look at in the neighbourhood (OR = 1.65), and access to places for PA (OR = 1.82) were associated with higher levels of LTPA in men. Among women, no significant relationships were observed between perceived environment and LTPA after adjusting for self-efficacy. The results provide additional support for the use of models in which gender is treated as a potential moderator of the link between the perceived environment and PA. Further, the results suggest the possibility of differential interventions to increase PA based on factors associated with gender.


Apolipoprotein E (APOE) genotype-associated disease risks: a phenome-wide, registry-based, case-control study utilising the UK Biobank.
The three main alleles of the APOE gene (ε4, ε3 and ε2) carry differential risks for conditions including Alzheimer's disease (AD) and cardiovascular disease. Due to their clinical significance, we explored disease associations of the APOE genotypes using a hypothesis-free, data-driven, phenome-wide association study (PheWAS) approach. We used data from the UK Biobank to screen for associations between APOE genotypes and over 950 disease outcomes using genotype ε3ε3 as a reference. Data was restricted to 337,484 white British participants (aged 37-73 years). After correction for multiple testing, PheWAS analyses identified associations with 37 outcomes, representing 18 distinct diseases. As expected, ε3ε4 and ε4ε4 genotypes associated with increased odds of AD (p ≤ 7.6 × 10-46), hypercholesterolaemia (p ≤ 7.1 × 10-17) and ischaemic heart disease (p ≤ 2.3 × 10-4), while ε2ε3 provided protection for the latter two conditions (p ≤ 3.7 × 10-10) compared to ε3ε3. In contrast, ε4-associated disease protection was seen against obesity, chronic airway obstruction, type 2 diabetes, gallbladder disease, and liver disease (all p ≤ 5.2 × 10-4) while ε2ε2 homozygosity increased risks of peripheral vascular disease, thromboembolism, arterial aneurysm, peptic ulcer, cervical disorders, and hallux valgus (all p ≤ 6.1 × 10-4). Sensitivity analyses using brain neuroimaging, blood biochemistry, anthropometric, and spirometric biomarkers supported the PheWAS findings on APOE associations with respective disease outcomes. PheWAS confirms strong associations between APOE and AD, hypercholesterolaemia, and ischaemic heart disease, and suggests potential ε4-associated disease protection and harmful effects of the ε2ε2 genotype, for several conditions. National Health and Medical Research Council of Australia.


Academic and Career Outcomes Following Sexual Assault in Early Adulthood: A Comparison of LGBQ+ and Heterosexual Women.
Young adults (aged 18-24) who identify as lesbian, gay, bisexual, or queer (LGBQ+) report high rates of sexual assault (SA) victimization, yet much of the research on adverse outcomes resulting from SA has overlooked LGBQ+ victims. A probability-based sample of 901 adults was recruited to examine the negative academic and career outcomes attributed to SA during early adulthood among LGBQ+ cisgender women. LGBQ+ women were more likely to report negative impacts on academic and career goals (e.g., changed course of study) and transitions (e.g., switched jobs) following SA victimization than heterosexual women. Implications for research and LGBQ+ services are discussed.


Comparative assessment of live cyprinid and salmonid movement networks in England and Wales.
Disease poses a significant threat to aquaculture. While there are a number of factors contributing to pathogen transmission risk, movement of live fish is considered the most important. Understanding live fish movement patterns for different aquaculture sectors is therefore crucial to predicting disease occurrence and necessary for the development of effective, risk-based biosecurity, surveillance and containment policies. However, despite this, our understanding of live movement patterns of key aquaculture species, namely salmonids and cyprinids, within England and Wales remains limited. In this study, networks reflecting live fish movements associated with the cyprinid and salmonid sectors in England and Wales were constructed. The structure, composition and key attributes of each network were examined and compared to provide insight into the nature of trading patterns and connectedness, as well as highlight sites at a high risk of spreading disease. Connectivity at both site and catchment level was considered to facilitate understanding at different resolutions, providing further insight into disease outbreaks, with industry wide implications. The study highlighted that connectivity through live fish movements was extensive for both industries. The salmonid and cyprinid networks comprised 2533 and 3645 nodes, with a network density of 5.81 × 10-4 and 4.2 × 10-4, respectively. The maximum network reach of 2392 in the salmonid network was higher, both in absolute terms and as a proportion of the overall network, compared to maximum network reach of 2085 in the cyprinid network. However, in contrast, the number of sites in the cyprinid network with a network reach greater than one was 513, compared to 171 in the salmonid network. Patterns of connectivity indicated potential for more frequent yet smaller scale disease outbreaks in the cyprinid industry and less frequent but larger scale outbreaks in the salmonid industry. Further, high connectivity between river catchments within both networks was shown, posing challenges for zoning at the catchment level for the purpose of disease management. In addition to providing insight into pathogen transmission and epidemic potential within the salmonid and cyprinid networks, the study highlights the utility of network analysis, and the value of accessible, accurate live fish movement data in this context. The application of outputs from this study, and network analysis methodology, to inform future disease surveillance and control policies, both within England and Wales and more broadly, is discussed.


Chronic parasite infections cause immune changes that could affect successful vaccination.
Several important issues must be considered when performing any vaccination in areas with high prevalence of geohelminths. Immunization of populations infected with geohelminths could be sub-optimal if the immune background is not taken into consideration. Immune modulation and deworming might be essential for effective protective vaccination. In addition, further animal models and clinical studies addressing these issues are required. Underscoring the importance of these issues, a recent report has highlighted several vaccination studies in which nematode-infected mice or pigs failed to mount efficient protective immune responses.


[Transition from intensive care to palliative care : A retrospective analysis of 102 consultation requests].
The transition of patients from the intensive care unit (ICU) to the palliative care (PC) ward often implies changes including establishing a palliative concept. Adaptation of therapeutic goals can be challenging for medical staff, patients and relatives; however, descriptions of these transition trajectories are rare. The aim of this retrospective study was to characterize the consultation requests of the ICU to the PC consultation team as well as the patients by a description of trajectories and interventions. Retrospective analysis of all patients receiving intensive care at RWTH Aachen University Hospital in 2019 for whom a PC consultation was requested. The patient population transferred from the ICU to the PC ward was compared with the non-transferred population. In each case, the primary consultation was evaluated regarding the following factors: question, vigilance, length of time from consultation request to its performance, and primary focus of the question. The question focus was categorized into "symptom control", "counselling" and "transfer" (tick options). In addition, a free text field was available for further notes. Exploration of diagnoses was complemented by accessing the electronic health records. A total of 102 consultation requests from the ICU to the PC ward were evaluated. The morbidity of patients was high, and most patients had at least one of the following diagnoses: pulmonary (62%), cardiovascular (61%), and/or neurological disease (55%). Of the patients 32 (31%) were transferred to the PC ward, among whom weakness (94%), fatigue (77%), anxiety (55%), pain (53%), and dyspnea (48%) were the most frequently noted symptoms. Of the transferred patients 5 (16%) could be discharged to home, nursing home, hospice or other. In total, 35 (34%) of all patients who were seen by palliative care specialists on ICUs in 2019 could be discharged alive. The most frequent reasons for nonadmission were lack of capacity of the PC ward (33%), dying while being on the waiting list (20%), and refusal by the patient (20%). Of the patients, 7 (26%) died within 48 h after they had been transferred to the PC ward. Performed consultation services "symptom control" (χ2 = 10.17; p < 0.05) and "counselling" (χ2 = 12.82; p < 0.001), which were requested by the intensive care physicians, showed a significant linkage with the respective intervention performed by the palliative care team. On the other hand, no statistically significant difference was found for requested and performed "transfer" of patients from ICUs to PC ward. Comparing the transferred versus non-transferred patient population, a significantly more frequent transfer of patients with malignant tumors (p = 0.00) was observed. The need for palliative care support in the ICUs exceeded the admission capacity of the PC ward. Future studies should further examine palliative care models in intensive care medicine.


The child as proband for future parental cardiometabolic disease: the 26-year prospective Princeton Lipid Research Clinics Follow-up Study.
To evaluate children's cardiovascular disease (CVD) risk factors as predictors of parents' subsequent CVD, type 2 diabetes mellitus (T2DM), and high blood pressure (HBP). We conducted a 26-year prospective follow-up of 852 5- to 19-year-old black and white schoolchildren (mean age, 12 years; Lipid Research Clinics, 1973-8), and parents (mean age, 40 years) from 519 families in Princeton Schools, Cincinnati, Ohio. Schoolchildren were reassessed in the Princeton Follow-up study 1999-2003 at mean age 39 years; CVD, T2DM, and HBP history of their 1038 parents were reassessed by mean age 66 years. We assessed relationships of childhood risk factors with parental CVD, T2DM, and HBP. Child-probands identified with triglyceride (TG) levels, blood pressure, low-density lipoprotein cholesterol levels, body mass index (BMI), and glucose level greater than and high-density lipoprotein cholesterol levels less than established cutoff points. Pediatric HBP (P=.006) and low high-density lipoprotein cholesterol (P=.018) were predictive of parental CVD at age ≤50 years. Pediatric HBP (P=.02) and high TG (P=.03) were predictive of parental CVD at age ≤60 years. Pediatric high TG (P=.009) and high low-density lipoprotein cholesterol (P=.04) were predictive of parental CVD by age 66 years. Pediatric high BMI (P=.0006) were predictive of parental T2DM. Pediatric high BMI (P=.003) and black race (P=.004) were predictive of parental HBP. Pediatric risk factors identify families with parents at increased risk for CVD, T2DM, and HBP, emphasizing the usefulness of the child as proband.


Two eating disorder preventive interventions reduce attentional biases in body-dissatisfied university women: A cluster randomized controlled trial.
This cluster randomized controlled trial evaluated the efficacy of participation in the Body Project-a cognitive-dissonance-based preventive intervention that reduces self-reported body dissatisfaction-for reducing body-dissatisfaction-related attentional biases. We hypothesized that women in a Body Project condition would show a greater reduction in attentional biases to weight-related images and words at postintervention than women in a wait-list control condition. Body-dissatisfied university women (N = 168; Mage = 20.50 ± 3.37 years; 42.0% White; MBMI = 23.08 ± 4.45 kg/m²) were randomly assigned to a Body Project, media psychoeducation (i.e., active control), or wait-list control condition. We assessed attentional biases via eye-gaze tracking and body satisfaction using the Body Shape Questionnaire, at baseline and postintervention. Self-reported outcomes from previous literature were replicated. Compared to wait-list, Body Project participation reduced attention to images of thin models (ps < .05; ds = .19, .24), but not to weight-related words. Compared to wait-list, the media psychoeducation condition reduced attention to fat-related images and words (ds = .17, .18). This study, which replicates previous self-report findings, is the first to find that two preventive interventions reduced an objective outcome (attentional bias to weight-related images) in body-dissatisfied women. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Nutritional deficiency in general practice: a systematic review.
Nutritional deficiency is an independent risk factor for mortality. Despite its clinical relevance, the prevalence in a primary care setting is poorly documented. We performed a systematic review of reported prevalence and clinical assessment of nutritional deficiency in general practice. From MEDLINE, Current Contents and EMBASE, we derived articles and checked the initially included ones for references on prevalence data. Of the eligible articles, we assessed the quality of research and results. We finally included eight studies. The prevalence ranged from 0 to 13%. However, the study populations were heterogeneous and all studies contained methodological flaws, especially selection bias. In addition, the clinical assessment differed between studies. Literature on the prevalence of nutritional deficiency within general practice is rare and provides disputable prevalence assessments.


When more is less: feedback effects in perceptual category learning.
Rule-based and information-integration category learning were compared under minimal and full feedback conditions. Rule-based category structures are those for which the optimal rule is verbalizable. Information-integration category structures are those for which the optimal rule is not verbalizable. With minimal feedback subjects are told whether their response was correct or incorrect, but are not informed of the correct category assignment. With full feedback subjects are informed of the correctness of their response and are also informed of the correct category assignment. An examination of the distinct neural circuits that subserve rule-based and information-integration category learning leads to the counterintuitive prediction that full feedback should facilitate rule-based learning but should also hinder information-integration learning. This prediction was supported in the experiment reported below. The implications of these results for theories of learning are discussed.


Toxicities of some heavy metals to the tadpoles of frog, Microhyla ornata (Dumeril & Bibron).
Static bioassays were conducted to determine the relative acute toxicities of five heavy metals (mercury, cadmium, copper, manganese and zinc) to 1-week-old and 4-week-old tadpoles of the frog, Microhyla ornata. Toxic effects were calculated on the basis of LC50 for 24 h, 48 h, 72 h and 96 h exposures at 25.5-26.0 degrees C. Mercury was the most toxic and zinc was the least toxic of the heavy metals tested. The sensitivity of the tadpoles to the heavy metals increased with increased age.


Normal pregnancy and delivery two years after adjuvant chemotherapy for grade III immature ovarian teratoma.
A 27-year-old woman with grade 3 immature teratoma of the ovary was treated with unilateral salpingo-oophorectomy and VAC combination chemotherapy. She received 6 postoperative courses, although initially 12 were planned. Chemotherapy had to be discontinued because of severe bone marrow toxicity. Eighteen months later the patient became pregnant and was ultimately delivered of a normal child. This is the second report of a successful pregnancy following VAC chemotherapy for immature teratoma.


Quantification of small joint space width, periarticular bone microstructure and erosions using high-resolution peripheral quantitative computed tomography in rheumatoid arthritis.
This paper aims to investigate the ability of a novel imaging technique, high-resolution peripheral quantitative computed tomography (HR-pQCT), to quantify joint space width at the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, and provide periarticular bone microstructure measurements (including volumetric density and morphometric indices). We also compared the sensitivity and specificity of HR-pQCT to detect erosions relative to plain radiography. HR-pQCT imaging of the MCP and PIP joints of the dominant hand was performed in 30 rheumatoid arthritis (RA) and control subjects matched for age, sex and dominant hand use. The joint space width was calculated by determining the number of voxels between three-dimensional images of the articular surfaces. Periarticular bone microstructure was quantified for the 2nd and 3rd MCP joints using standard analysis. The presence of erosions was confirmed by viewing both two- and three-dimensional images of the joints. Quantitative measures of joint space width and periarticular bone microstructure were obtained with precision. Although not powered to detect differences between RA and control subjects, we identified a trend to narrowing of the 2nd MCP joints in RA (mean difference 250 μm, p=0.057). RA erosions most frequently occurred at the metacarpal head of the MCP joint, and HR-pQCT identified erosions in 24.7% more joints compared to plain radiography. This is the first study to exploit the quantitative capabilities of HR-pQCT to provide joint space width measurements at the MCP and PIP joints. We provide further proof that HR-pQCT improves erosion detection and yields reproducible periarticular bone microstructure measurements.


Variability in Early Ahmarian lithic technology and its implications for the model of a Levantine origin of the Protoaurignacian.
This paper re-examines lithic technological variability of the Early Ahmarian, one of the early Upper Palaeolithic cultural entities in the Levant, which has often been regarded as a precursor of the Protoaurignacian (the early Upper Palaeolithic in Europe) in arguments for the occurrence of a cultural spread in association with the dispersal of Homo sapiens from the Levant to Europe. Using quantitative data on several lithic techno-typological attributes, we demonstrate that there is a significant degree of variability in the Early Ahmarian between the northern and southern Levant, as previously pointed out by several researchers. In addition, we suggest that the technology similar to the southern Early Ahmarian also existed in the northern Levant, i.e., the Ksar Akil Phase 4 group (the KA 4 group), by introducing new Upper Palaeolithic assemblages from Wadi Kharar 16R, inland Syria. We then review currently available stratigraphic records and radiocarbon dates (including a new date from Wadi Kharar 16R), with special attention to their methodological background. As a result, we propose alternative chronological scenarios, including one that postulates that the southern Early Ahmarian and the KA 4 group appeared later than the northern Early Ahmarian with little or no overlap. On the basis of the alternative scenarios of chronological/geographical patterns of the Early Ahmarian variability, we propose four possible relationships between the Protoaurignacian and the Early Ahmarian, including a new scenario that the appearance of the Protoaurignacian preceded those of similar technological entities in the Levant, i.e., the southern Early Ahmarian and the KA 4 group. If the last hypothesis is substantiated, it requires us to reconsider the model of a Levantine origin of the Protoaurignacian and its palaeoanthropological implications.


Longitudinal evaluation of a weight reduction program for patients on peritoneal dialysis.
Patients on peritoneal dialysis (PD) are exposed to glucose-based dialysate solutions with consequent risk of obesity and its attendant health problems. We wished to examine the role of changes in dialysis prescription, individualized dietaryinput, and exercise on body weight and composition. A 1 year, prospective interventional study integrating the care of the renal nurse, dietitian, and physiotherapist to support, educate, and encourage overweight patients on PD in a weight-reduction program. Patients were considered for the study if they had been on PD for more than 3 months, had a body mass index (BMI) > 25, and were considered medically fit to undergo the planned exercise program. Recruitment was intentionally limited to a maximum of 12 patients to facilitate group interaction. Weight, BMI, and bioimpedance were measured every 3 months. 8 of 11 enrolled patients completed the study; 3 received transplants. There was a significant fall in median body weight at initiation, from 94.6 kg to 92.4 kg at 6 months and 89.5 kg at 12 months (p = 0.017). This equates to a reduction in BMI from 33.2 (range 26.6 - 38.4) kg/m2 at initiation to 32.1 (range 24.5 - 37.6) kg/m2 at 6 months and 32.1 (range 23.9 - 36.5) kg/m2 at 12 months. There were no significant changes in total body water, lean body mass, or percentage body fat during the study. 7 of 8 patients achieved significant weight loss during the study. The use of an informal group setting motivated patients to continue with exercise and sensible eating patterns. This study demonstrates that, with adequate support, PD patients can achieve and maintain weight loss.


On-column refolding purification of DT389-hIL13 recombinant protein expressed in Escherichia coli.
Protein refolding is a bottleneck in the production of therapeutic proteins from inclusion bodies. In recent years, several studies have described on-column refolding of recombinant proteins. DT389-hIL13 is a recombinant protein that targets the glioma. In our study, the recombinant protein DT389-hIL13 was expressed in Escherichia coli (E. coli). The isolated inclusion bodies were refolded using size exclusion chromatography (SEC) and further purified using anion exchange chromatography. Three different methods of SEC on-column refolding were studied. In vitro tests on U251 cells showed that the recombinant protein could effectively inhibit the proliferation of U251 cells, especially the protein refolded by urea and pH gradient method. The half-maximal inhibitory concentration (IC50) of 0.887 nM was achieved with this new method, unlike an IC50 of 11.4 nM achieved in the non-gradient method.


Purification and N-terminal sequencing of style glycoproteins associated with self-incompatibility in Petunia hybrida.
We report isolation and N-terminal amino acid sequencing of three style glycoproteins, which segregate with three S (self-incompatibility) alleles of Petunia hybrida. The S-glycoproteins were expressed mainly in the upper part of the pistil and showed an increasing concentration during flower development. The glycoproteins were purified by a combination of ConA-Sepharose and cation exchange fast protein liquid chromatography. The amount of S-glycoproteins recovered from style extracts varied from 0.5 to 1.6 micrograms per style, which was 40-60% of the amount recovered by a simplified analytical method. N-terminal amino acid sequences of S1-, S2- and S3-glycoprotein showed homology within the fifteen amino terminal residues. These amino acid sequences were compared with the previously published sequences of S-glycoproteins from Nicotiana alata and Lycopersicon peruvianum.


Assessment of Condylar Shape through Digital Panoramic Radiograph among Nepalese Population: A Proposal for Classification.
Panoramic radiograph is the first and most commonly advised radiograph for screening of temporomandibular joints/condyles. Different shapes of the mandible have been discussed by various authors with no consensus for a definite classification for condyle shape. This study was conducted with the objective to observe various shapes of condyles, symmetry of bilateral condyles, and variations of condyle shapes among males and females. This cross-sectional study was conducted on digital panoramic radiographs available at a tertiary center of Lalitpur from 25.12.2020 to 20.06.2021 after ethical approval from the institutional review board (reference no. 077/078/27). Panoramic radiographs were selected on the basis of inclusion and exclusion criteria, and various shapes of condyles were noted on HP 15 inch flat LED monitor (1280 × 1024). The collected data was analyzed using SPSS (chi-square test: a p value of < 0.05 was considered significant). Intra- and interobserver agreement was observed for condylar shapes. Among the selected 850 panoramic radiographs (1700 condyles), most of them, i.e., 1343 (79%), were round/oval, followed by flattened, i.e., 149 (8.76%), diamond/angled, i.e., 93 (5.47%), crooked finger shaped, i.e., 28 (1.6%), and mixed, i.e., 46 (2.7%), and the least common shape observed was bifid, i.e., 40 (2.3%) (18 (2.1%) left condyle and 22 (2.6%) right condyle). Six different types of condyle shapes were noted: type I, oval; type II, flat; type III, diamond; type IV, mixed; type V, bifid; and type VI, crooked finger among the study population of Lalitpur.


[Fatal poisonings with propoxur].
The insecticide propoxur (2-isopropoxyphenyl-N-methylcarbamate) acts by blocking cholinesterase. This inhibition is fast and, unlike that brought about by organophosphorus compounds, reversible. The toxicity of propoxur to man is stated to be low compared with that of parathion. Only a small number of fatal intoxications have been published; at the Würzburg University Institute of Legal Medicine eight cases have been observed since 1978. In seven cases death occurred after deliberate oral ingestion of solutions of propoxur with suicidal intent, while in the other, intoxication was accidental, following inhalation of an aerosol containing propoxur. Organs and body fluids were investigated toxicologically and histologically. The results are presented and discussed. Special attention is paid to the combination of propoxur and alcohol.


Metabolic effects of reduced growth hormone action in fatty liver disease.
Adult growth hormone (GH) deficiency is associated with fatty liver disease and shows several features of the metabolic syndrome. Vice versa obesity is characterized as a state of low GH function. Here, we aimed to define the role of hepatic GH signaling and its metabolic consequences in non-alcoholic fatty liver disease. In humans, GHR and IGF-1 levels were determined in liver samples of 29 obese patients with non-alcoholic steatohepatitis (NASH) or simple steatosis. Cellular effects of GH on insulin signaling were investigated in GH receptor (GHR) knockdown HepG2 cells. Hepatic IGF-1 expression levels reflecting GH action were significantly lower and fasting glucose concentrations higher in patients with NASH than in patients with simple steatosis. GHR knockdown in hepatocytes resulted in a scenario of high glucose output displayed by reduced glycogen content, increased gluconeogenesis and diminished insulin signaling. Our data suggest that GH signaling in the liver is diminished in patients with NASH and associated with deteriorated hepatic insulin sensitivity and metabolic activity. Reduced hepatic GH action might contribute to insulin resistance in obese patients with NASH.


Simplified identification of bacteria belonging to the genus Salmonella.
A new, simplified procedure for identification of bacteria belonging to the genus Salmonella is reported. By this procedure which is a new combination of well know tests, Salmonella spp. are easily and reproducibly differentiated from non Salmonella spp. after 6 h of incubation at 37 degrees C.


Unrecognized atypical tuberous sclerosis diagnosed with CT.
Past experience in this hospital has shown that the neuroradiological diagnosis of tuberous sclerosis is often made before the diagnosis is clinically suspected. We present a child in such a circumstance in whom axial and coronal CT demonstrated significant neoplastic progression of this disease. The presenting symptom was merely that of increased intracranial pressure.


Intra-articular fracture patterns associated with tibial shaft fractures: more than just the posterior malleolus.
The association of tibial shaft fractures (TSFs) with posterior malleolar fractures is well described. The purpose of this study was to identify specific radiographic parameters that are predictive of any pattern of associated distal intra-articular fractures in TSFs. All TSFs presenting over a 6-year period were identified. A radiographic review of plain radiographs and CT scans included: identification of any associated ankle fracture, classification using the OTA System, measurements of the TSF obliquity angle (FOA), relative distance from distal extent of the TSF to plafond (DFP%), and presence and level of any associated fibular fractures. Patients with and without associated ankle fractures were statistically compared. Multivariate logistic regression determined independent predictors of associated ankle fractures. 405 TSFs in 397 patients were identified, with 145 TSFs with associated distal intra-articular fractures. There were 94 (23.2%) posterior malleolar fractures, 19 (13.1%) medial malleolar fractures, 42 (29.0%) lateral malleolar fractures involving the syndesmosis and 14 (9.7%) Chaput fragments. Multivariate regression demonstrated AO/OTA classification type 42-A1, 42-B1 or 42-C1 (OR 2.3 [95% CI 1.3-4.0]; p = 0.003), FOA greater than 45° (OR 2.7 [95% CI 1.5-4.8]; p = 0.001) and DFP% less than 33% (OR 4.1 [95% CI 2.0-9.0]; p = 0.005) were independent correlates of associated ankle fractures regardless of mechanism of injury. Different patterns of intra-articular fractures beyond posterior malleolar fractures can occur in TSFs. Fracture angles greater than 45° and extent into the distal 33% of the tibial shaft are independent predictors of distal intra-articular fractures in TSFs regardless of mechanism of injury. Diagnostic Level III.


Role of spiramycin in prevention of fetal toxoplasmosis.
The aim of this study is to evaluate the efficacy of spiramycin in prevention of mother-to-child transmission of Toxoplasma gondii infection. Patients within first trimester of their pregnancy with Toxoplasma IgM positivity (>0.65 index, ELISA, VIDAS) and IgG positivity (>8 IU/ml), who had low IgG avidity (<0.50 index, ELISA, Architet) were considered as having acute toxoplasmosis. These patients who had amniocentesis at the 19th-21st week of pregnancy were examined for the detection of Toxoplasma DNA. Detailed ultrasonographic examinations performed between the 20th and 24th gestational weeks and the mothers and babies were followed for at least one year. Out of 61 patients, 55 (90.2%) had received Spy prophylaxis while 6 (9.8%) cases refused Spy prophylaxis. Toxoplasma PCR test was found to be positive in amniotic fluid of 4 (6.6%) patients obtained by amniocentesis at the 19th-21st week of pregnancy. All four of these patients had refused Spy prophylaxis had positive Toxoplasma PCR in amniotic fluid (p < 0.01). Our results seem to encourage the use of spiramycin in women with toxoplasmosis during pregnancy.


Hepatic fibrosis: a manifestation of the liver disease evolution in patients with Ataxia-telangiectasia.
Ataxia-telangiectasia (A-T) is a DNA repair disorder characterized by changes in several organs and systems. Advances in clinical protocols have resulted in increased survival of A-T patients, however disease progression is evident, mainly through metabolic and liver changes. To identify the frequency of significant hepatic fibrosis in A-T patients and to verify the association with metabolic alterations and degree of ataxia. This is a cross-sectional study that included 25 A-T patients aged 5 to 31 years. Anthropometric data, liver, inflammatory, lipid metabolism and glucose biomarkers (oral glucose tolerance test with insulin curve-OGTT) were collected. The Cooperative Ataxia Rating Scale was applied to assess the degree of ataxia. The following were calculated: Homeostasis Model Assessment-Insulin Resistance, Homeostasis Model Assessment-Adiponectin (HOMA-AD), Matsuda index, aspartate aminotransferase (AST): platelet ratio index, nonalcoholic fatty liver disease fibrosis score and BARD score. Liver ultrasonography and transient liver elastography by FibroScan® were performed. Significant hepatic fibrosis was observed in 5/25 (20%). Patients in the group with significant hepatic fibrosis were older (p < 0.001), had lower platelet count values (p = 0.027), serum albumin (p = 0.019), HDL-c (p = 0.013) and Matsuda index (p = 0.044); and high values of LDL-c (p = 0.049), AST (p = 0.001), alanine aminotransferase (p = 0.002), gamma-glutamyl transferase (p = 0.001), ferritin (p = 0.001), 120-min glycemia by OGTT (p = 0.049), HOMA-AD (p = 0.016) and degree of ataxia (p = 0.009). A non-invasive diagnosis of significant hepatic fibrosis was observed in 20% of A-T patients associated with changes in liver enzymes, ferritin, increased HOMA-AD, and the severity of ataxia in comparison with patients without hepatic fibrosis.


Reappraisal of risk factors for monoclonal gammopathy of undetermined significance.
A number of epidemiologic studies have demonstrated associations between obesity and diabetes and the risk of monoclonal gammopathy of undetermined significance (MGUS). However, since MGUS is an asymptomatic condition we evaluated whether these are true associations or the result of detection-bias. We conducted a nested case-control study using a large primary-care database. Cases were defined as those with incident diagnosis of MGUS. For every case, four eligible controls matched on age, sex, practice site, and duration of follow-up were selected. Exposure variables included obesity and diabetes (including antidiabetic therapies) as well as other metabolic risk factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. The study included 2363 MGUS patients and 9193 matched controls. In the primary analysis, obesity and diabetes were associated with higher MGUS risk with an adjusted ORs of 1.15 (95% CI 1.02-1.29) and 1.30 (95% CI 1.13-1.50), respectively. However, after adjustment to the number of laboratory tests prior to the MGUS diagnosis, there was no association between obesity and diabetes and MGUS risk (ORs of 1.08, 95% CI 0.96-1.22 and 1.08, 95% CI 0.93-1.25, respectively). In an additional analysis of antidiabetic therapies and MGUS risk, there was a nonsignificant decrease in MGUS risk among diabetes patients treated with metformin alone compared to subjects without diabetes (OR 0.77, 95% CI 0.56-1.05). In summary, while previously described risk factors for MGUS might be the result of detection bias, metformin should be further evaluated as a possible chemoprevention modality. Am. J. Hematol. 91:581-584, 2016. © 2016 Wiley Periodicals, Inc.


Mesh versus acellular dermal matrix in immediate implant-based breast reconstruction - A prospective randomized trial.
Comparative studies on the use of meshes and acellular dermal matrices (ADM) in implant-based breast reconstruction (IBBR) have not yet been performed. This prospective, randomized, controlled, multicenter pilot study was performed at four Austrian breast cancer centers. Fifty patients with oncologic or prophylactic indication for mastectomy and IBBR were randomized to immediate IBBR with either an ADM (Protexa(®)) or a titanized mesh (TiLOOP(®) Bra). Complications, failed reconstruction, cosmetic outcome, patients' quality of life and the thickness of the overlying tissue were recorded immediately postoperatively and 3 and 6 months after surgery. 48 patients participated in the study (Protexa(®) group: 23; TiLOOP(®) Bra group: 25 patients). The overall complication rate was 31.25% with similar rates in both groups (Protexa(®) group: 9 versus TiLOOP(®) Bra group: 6; p = 0.188). There was a higher incidence of severe complications leading to failed reconstructions with implant loss in the Protexa(®) group than in the TiLOOP(®) Bra group (7 versus 2; p < 0.0001). An inverted T-incision technique led to significantly more complications and reconstructive failure with Protexa(®) (p = 0.037, p = 0.012, respectively). There were no significant differences in patients' satisfaction with cosmetic results (p = 0.632), but surgeons and external specialists graded significantly better outcomes with TiLOOP(®) Bra (p = 0.034, p = 0.032). This pilot study showed use of TiLOOP(®) Bra or Protexa(®) in IBBR is feasible leading to good cosmetic outcomes and high patient satisfaction. To validate the higher failure rates in the Protexa(®) group, data from a larger trial are required. NCT02562170.


Comprehensive Genome-Wide Identification and Transcript Profiling of GABA Pathway Gene Family in Apple (Malus domestica).
γ-Aminobutyric Acid (GABA), a four-carbon non-protein amino acid, is a significant component of the free amino acid pool in most prokaryotic and eukaryotic organisms. GABA is involved in pH regulation, maintaining C/N balance, plant development and defence, as well as a compatible osmolyte and an alternative pathway for glutamate utilization via anion flux. Glutamate decarboxylase (GAD, EC 126.96.36.199) and GABA transaminase (GABA-T, EC 22.214.171.124) are two key enzymes involved in the synthesis and metabolism of GABA. Recently, GABA transporters (GATs), protein and aluminium-activated malate transporter (ALMT) proteins which function as GABA receptors, have been shown to be involved in GABA regulation. However, there is no report on the characterization of apple GABA pathway genes. In this study, we performed a genome-wide analysis and expression profiling of the GABA pathway gene family in the apple genome. A total of 24 genes were identified including five GAD genes (namely MdGAD 1-5), two GABA-T genes (namely MdGABA-T 1,2), 10 GAT genes (namely GAT 1-10) and seven ALMT genes (namely MdALMT1-7). These genes were randomly distributed on 12 chromosomes. Phylogenetic analyses grouped GABA shunt genes into three clusters-cluster I, cluster II, and cluster III-which had three, four, and five genes, respectively. The expression profile analysis revealed significant MdGAD4 expression levels in both fruit and flower organs, except pollen. However, there were no significant differences in the expression of other GABA shunt genes in different tissues. This work provides the first characterization of the GABA shunt gene family in apple and suggests their importance in apple response to abiotic stress. These results can serve as a guide for future studies on the understanding and functional characterization of these gene families.


Acylation of arginine in goserelin-loaded PLGA microspheres.
Acylation of peptides is a well-known but unwanted phenomenon in polyester matrices such as poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres used as controlled release formulations. Acylation normally occurs on lysine residues and the N-terminus of the peptide. The purpose of the present work was to assess other possible acylation sites on peptides. Goserelin was used as a model peptide that lacks lysine and a free N-terminus, but contains other nucleophilic residues, i.e. serine, tyrosine and arginine, which potentially can be acylated. Goserelin loaded PLGA microspheres were prepared by a double emulsion solvent evaporation technique. Liquid chromatography ion-trap mass spectrometry (LC-ITMS) was used for determining and monitoring acylation of released goserelin. It is demonstrated that arginine is subjected to acylation with glycolic acid and lactic acid units of PLGA, which was followed by loss of NH3 from the guanidine group to obtain 2-oxazolin-4-one and 5-methyl-2-oxazolin-4-one residues with masses that are 41 and 55Da higher, respectively, than the native goserelin. There was no evidence for acylation of serine and tyrosine in goserelin. Our results demonstrate that beside lysine also acylation of arginine can occur in peptides and proteins that are loaded and released from PLGA matrixes.


Long-term survival following definitive radiation therapy for recurrence or oligometastases in gynecological malignancies: A landmark analysis.
Radiation therapy (RT) may improve outcomes for patients with oligometastatic cancer. We sought to determine if there are long-term survivors treated with definitive RT for recurrent or oligometastatic gynecological cancer (ROMGC), and to evaluate the clinical and disease characteristics of these patients. We performed a landmark analysis in 48 patients with ROMGC who survived for ≥5 years following definitive RT of their metastasis. Patient characteristics were extracted from the medical record. DFS was modeled using the Kaplan-Meier method. This cohort included 20 patients (42%) with ovarian cancer, 16 (33%) with endometrial cancer, 11 (23%) with cervical cancer, and one (2%) with vaginal cancer. The sites of ROMGC were the pelvic (46%), para-aortic (44%), supraclavicular (7%), mediastinal (4%), axillary (4%) lymph nodes and the lung (5.5%). Median total RT dose and fractionation were 62.1 Gy and 2.1 Gy/fraction; one patient was treated with SBRT. 32 patients (67%) received chemoradiation; these patients had higher rates of median DFS than those treated with RT alone (93 vs. 34 months, P = 0.05). At median follow-up of 11.7 years, 11 (23%) patients had progression of disease. 20 (42%) patients had died, 9 (19%) died from non-gynecologic cancer and 8 (17%) from gynecologic cancer (three were unknown). 25 (52%) patients were alive and disease-free (10 initially had endometrial cancer [63% of these patients], eight had cervical cancer [73%], six had ovarian cancer [30%], one had vaginal cancer [100%]). Long-term survival is possible for patients treated with definitive RT for ROMG, however randomized data are needed to identify which patients derive the most benefit.


Molecular cloning and expression profile of putative antilipopolysaccharide factor in Chinese shrimp(Fenneropenaeus chinensis).
A new antimicrobial protein gene of the anti-lipopolysaccharide factor family (tentatively named as ALFFc) has been cloned from hemocytes of the Chinese shrimp Fenneropenaeus chinensis by rapid amplification of 3' and 5' complementary DNA ends with polymerase chain reaction. The full-length complementary DNA of ALFFc consists of 600 bp with a 369-bp open reading frame, encoding 123 amino acids. The deduced peptide contains a putative signal peptide of 25 amino acids and mature peptide of 98 amino acids. The molecular mass of the deduced mature peptide is 13799.16 Da. It is highly cationic, with a theoretical pI of 10.3. The deduced amino acid sequence of ALFFc showed 56% homology with sequences of Tachypleus tridentatus and L. polyhemus. The tissue expression profile of this gene was studied by Northern blot, and ALFFc transcripts were mainly detected in hemocytes, gill, and intestine. RNA in situ hybridization showed that ALFFc was constitutively expressed in hemocytes. Capillary electrophoresis reverse transcriptase PCR was used to quantify the variation of messenger RNA transcription level during the artificial infection process with Vibrio anguillarum. Significant enhancement of ALFFc transcription appeared during the first 24 hours in response to Vibrio infection. These results provide useful information for understanding the function of ALFFc in shrimp.


Factors associated with inpatient readmission among managed care enrollees with COPD.
To assess factors associated with inpatient readmission among a US managed care population with chronic obstructive pulmonary disease (COPD). COPD is often accompanied by intermittent acute exacerbations, which may result in hospitalizations. These exacerbations are often associated with an increased frequency of subsequent exacerbations, which may lead to inpatient readmissions. We assessed US managed care claims data for enrollees≥40 years old with an inpatient admission with a primary diagnosis of COPD (ICD-9-CM codes 491.xx, 492.xx or 496.xx) between 1 January 2010 and 31 December 2013 (discharge date of first observed inpatient admission defined the "index date"). Patients were required to be continuously enrolled for ≥12 months before the index date. Two non-mutually exclusive cohorts were analyzed: (1) patients with ≥30 days of post-index date continuous enrollment (to evaluate 30-day readmission) and (2) patients with ≥90 days of post-index date continuous enrollment (to evaluate 90-day readmission). Logistic regression evaluated the association between patient characteristics and risk of 30- and 90-day COPD-related and all-cause readmission. After applying selection criteria, 140,981 patients had ≥30 days of enrollment post-index date, and 123,545 patients had ≥90 days of enrollment post-index date. Within 30 days, nearly 20% of patients had an all-cause readmission and 7% had a COPD-related readmission. Within 90 days, 28% had an all-cause readmission and 12% had a COPD-related readmission. Logistic regression indicated that longer length of stay, older age, greater comorbidity burden, specific comorbidities and COPD complexity were associated with significantly greater odds of COPD-related 30- and 90-day readmission. Results for all-cause readmission were generally similar. Many of the factors associated with inpatient readmission documented here can be ascertained at discharge and may be used to inform discharge plans, with the end goal of improving patient outcomes, including reducing the risk of readmission.


Extraction, purification and anti-osteoporotic activity of a polysaccharide from Epimedium brevicornum Maxim. in vitro.
Osteoporosis is the most widespread metabolic bone disease characterized by decreased bone mass and bone quality, and its diagnosis and treatment remains challenging. To date, medicinal plants have received increasing attention from researchers for researching effective and less toxic therapeutic ingredients, including polysaccharide, to treat osteoporosis. The present study aims to evaluate the osteoprotective effects of a polysaccharide (EBP) from Epimedium brevicornum in glucocorticoid-induced osteoporosis in vitro and investigate the underlying mechanism. EBP (25 and 100 μg/ml) pretreatment could significantly prevent decreased cell proliferation of osteoblasts (OBs) treated only with 100 μM of dexamethasone (Dex) via induction of apoptosis. The osteoblastic differentiation of EBP pretreatment on OBs at early and later phase was further confirmed by the increased alkaline phosphatase (ALP) activity and calcium content, respectively. Meanwhile, the increased expression of cleaved caspase-3 and Bax, as well as a decrease of Bcl-2 and the phosphorylation of PI3K, Akt and mTOR protein in Dex-treated OBs were totally reversed by EBP pretreatment. Moreover, the protein expression of Lrp-5, β-catenin, Runx2 and Osx were significantly up-regulated in the presence of EBP pretreatment. In conclusion, these results demonstrated that EBP pretreatment may be a potential therapeutic agent for patients with glucocorticoid-induced osteoporosis (GIO).


Tissue transglutaminase catalyzes the formation of alpha-synuclein crosslinks in Parkinson's disease.
In Parkinson's disease (PD), conformational changes in the alpha-synuclein monomer precede the formation of Lewy bodies. We examined postmortem PD and undiseased (control) substantia nigra for evidence of pathological crosslinking of alpha-synuclein by tissue transglutaminase (tTG) using immunohistochemistry, immunoprecipitation, and Western blot. Consistent with previous reports, we found that both tTG and its substrate-characteristic N(epsilon)-(gamma-glutamyl)-lysine crosslink are increased in PD nigral dopamine neurons. Furthermore, both the tTG protein and its substrate crosslink coprecipitated with alpha-synuclein in extracts of PD substantia nigra. Unexpectedly, the isodipeptide crosslink was detected in the alpha-synuclein monomer as well as in higher molecular mass oligomers of alpha-synuclein. Although the intramolecularly crosslinked alpha-synuclein monomer was present in control tissue, it was highly enriched in PD substantia nigra. Conversely, significantly less uncrosslinked alpha-synuclein remained in the postimmunoprecipitate lysate of PD tissue than in control. Crosslinked alpha-synuclein, formed at the expense of the total alpha-synuclein monomer, correlated with disease progression. These results demonstrate that much of the alpha-synuclein monomer in PD nigra is crosslinked by tTG and thus may be functionally impaired. This modification appears to be an early step in PD pathogenesis, preceding the aggregation of alpha-synuclein in Lewy bodies.


Therapy-induced microenvironmental changes in cancer.
In the past decade, the focus of tumor biology research has been switching from the functional dissection of oncogenes and tumor suppressor genes to investigation of the cross-talk between tumor cells and their microenvironment. Tumorigenesis requires the organized assembly of cancer cells with non-malignant cells and non-cellular stroma, resembling an abnormal organogenesis. This process can be modulated by local cellular stress responses, such as senescence, ER stress and autophagy, and inflammatory and immunosuppressive cells and effector molecules within the tumor microenvironment (TME). Various cellular stress responses and cell death modalities are triggered in response to chemotherapies, radiotherapies, and targeted therapies (including immunotherapies). The exposure of immunostimulatory factors could (re)awaken anti-tumor immunity. Unexpectedly, the gut microbial flora is becoming recognized as an important external modulator of the TME. We will discuss in detail the TME changes that take place after certain cancer therapies, highlighting the importance of cellular stress responses, tumor-infiltrating immune cells, and microbiota-derived factors.


Reducing ambulance conveyance for older people with and without dementia: evidence of the role of social care from a regional, year-long service evaluation using retrospective routine data.
Older people, especially those with dementia, have a high risk of deterioration following admission to hospital. More than 60% of older people attended by South Central Ambulance Service (SCAS) clinicians are conveyed to hospital, although many conveyances may not have been due to life-threatening conditions. We aimed to understand patterns of conveyance and alternative referral pathways used following ambulance attendance to an older person. Service evaluation, using routinely collected, anonymised electronic records. Electronic records of people aged ≥75 years for whom an ambulance was dispatched between April 2016 and March 2017 within the geographical boundaries of SCAS NHS Foundation Trust, who were alive on arrival of the ambulance. Conveyance rates are described according to patient and emergency-call characteristics. Logistic regression was used to produce adjusted odds ratios for conveyance. Alternative referral pathways used are described. Of 110,781 patients attended, 64% were conveyed to hospital. Factors associated with reduced odds of conveyance included out-of-hours calls (adjusted odds ratio (aOR) 0.82 [0.79-0.85]), living alone with a care package or with family plus care package (aOR 0.66 [0.62-0.69]; aOR 0.58 [0.54-0.62] respectively) and a record of dementia (0.91 [0.87-0.96]). Living in a nursing home was associated with an increased risk of conveyance (aOR 1.25 [1.15-1.36]). Patients with dementia with more income were significantly less likely to be conveyed than those with less income. Alternative referral services were used in 22% of non-conveyed patients, most commonly GP, out-of-hours and falls services. People aged ≥75 years have high rates of conveyance, which are influenced by factors such as out-of-hours calls, dementia and receipt of social care. Low use of alternative referral services may reflect limited availability or difficulty in access. A better understanding of how these factors influence ambulance clinician decision-making is integral to improvement of outcomes for older people.


Impact of HIV impact on outcomes of deep-brain stimulation of the subthalamic nucleus for Parkinson's disease.
Middle-aged persons living with HIV (PLHIV) have a heightened risk of more concomitant age-related comorbidities that are acknowledged as signs of poorer prognosis after deep-brain stimulation of the subthalamic nucleus (STN-DBS) at younger-than-expected ages. To assess the beneficial and adverse effects of STN-DBS in PLHIV with Parkinson's disease (PD). We retrospectively included nine PLHIV with PD who had sustained virological control. Patients were followed up for 7 ± 4 years. Patients' mean ages at PD onset and STN-DBS were 45 ± 15 and 53 ± 16 years, respectively. At STN-DBS, mean HIV infection and PD durations were 15 ± 12 and 8 ± 4 years, respectively. STN-DBS significantly improved 1-year Unified Parkinson's Disease Rating Scale (UPDRS)-III scores (71%), daily off-time (63%), motor fluctuations (75%) and daily levodopa-equivalent dose (68%); mean 5-year UPDRS-III score and motor fluctuation improvements remained ~45%. Impulse control disorders (affecting 6/9 patients) fully resolved after STN-DBS. Postoperative course was uneventful. No serious adverse events occurred during follow-up. Our findings indicate that STN-DBS is a safe and effective treatment for PLHIV with PD.


Intracellular oxygen metabolism during bovine oocyte and preimplantation embryo development.
We report a novel method to profile intrcellular oxygen concentration (icO2) during in vitro mammalian oocyte and preimplantation embryo development using a commercially available multimodal phosphorescent nanosensor (MM2). Abattoir-derived bovine oocytes and embryos were incubated with MM2 in vitro. A series of inhibitors were applied during live-cell multiphoton imaging to record changes in icO2 associated with mitochondrial processes. The uncoupler carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) uncouples mitochondrial oxygen consumption to its maximum, while antimycin inhibits complex III to ablate mitochondrial oxygen consumption. Increasing oxygen consumption was expected to reduce icO2 and decreasing oxygen consumption to increase icO2. Use of these inhibitors quantifies how much oxygen is consumed at basal in comparison to the upper and lower limits of mitochondrial function. icO2 measurements were compared to mitochondrial DNA copy number analysed by qPCR. Antimycin treatment increased icO2 for all stages tested, suggesting significant mitochondrial oxygen consumption at basal. icO2 of oocytes and preimplantation embryos were unaffected by FCCP treatment. Inner cell mass icO2 was lower than trophectoderm, perhaps reflecting limitations of diffusion. Mitochondrial DNA copy numbers were similar between stages in the range 0.9-4 × 106 copies and did not correlate with icO2. These results validate the MM2 probe as a sensitive, non-toxic probe of intracellular oxygen concentration in mammalian oocytes and preimplantation embryos.


Aneurysmal bone cyst of the orbit.
Proptosis of the left eye had developed in a 42-year-old woman for 2 months' duration. Roentgenogram studies showed a mass in the roof of the left orbit and bone erosion. An excisional biopsy confirmed the presence of an aneurysmal bone cyst. To the authors' knowledge, the patient is the oldest reported patient who has this uncommon orbital lesion.


Quantitative assessment of left ventricular wall motion by two-dimensional echocardiography: validation during reversible ischemia in the conscious dog.
This study was designed to test the accuracy of echocardiographic radial shortening measurements during variable degrees of regional dysfunction produced by 14 transient (less than or equal to 10 min) coronary occlusions (8 left anterior descending coronary artery, 6 left circumflex coronary artery) followed by up to 24 h of reperfusion in chronically instrumented conscious dogs. Independent measurement of regional myocardial thickening was obtained using epicardial pulsed Doppler probes and served as a standard for comparison. Radial shortening fraction was derived from two-dimensional short-axis views along 12 equidistant radii. Six reference systems from the epicardial and endocardial centers of geometry (centroids) in a fixed or a floating position were explored. In the ischemic zone, percent thickening fraction averaged 22 +/- 5% at baseline, decreased to -4 +/- 4% during occlusion and gradually returned to baseline values after reperfusion. Percent change in radial shortening correlated significantly with percent change in thickening fraction in the ischemic zone. The worst correlation was seen with the floating endocardial centroid (r = 0.68), and the best was observed with the epicardial floating reference (r = 0.91). Moreover, the epicardial floating reference provided narrower 95% confidence limits of radial shortening and less heterogeneity among radii than did fixed reference systems. Thus, compared with an independent standard, echocardiographic measurement of radial shortening from the short axis provided recognition of discrete grades of regional dysfunction induced by transient reversible ischemia. This technique may be amenable for serial assessment of regional function after interventions on the ischemic myocardium.


Prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models.
The effects of AT1 receptor blocker, telmisartan, and the ACE inhibitor, ramipril, were tested head-to head and in combination on stroke prevention in hypertensive rats and on potential neuroprotection in acute cerebral ischemia in normotensive rats. Prevention study: Stroke-prone spontaneously hypertensive rats (SHR-SP) were subjected to high salt and randomly assigned to 4 groups: (1) untreated (NaCl, n = 24), (2) telmisartan (T; n = 27), (3) ramipril (R; n = 27) and (4) telmisartan + ramipril (T+R; n = 26). Drug doses were selected to keep blood pressure (BP) at 150 mmHg in all groups. Neurological signs and stroke incidence at 50% mortality of untreated SHR-SP were investigated. Intervention study: Normotensive Wistar rats were treated s.c. 5 days prior to middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Groups (n = 10 each): (1) sham, (2) vehicle (V; 0.9% NaCl), (3) T (0.5 mg/kg once daily), (4) R (0.01 mg/kg twice daily), (5) R (0.1 mg/kg twice daily) or (6) T (0.5 mg/kg once daily) plus R (0.01 mg/kg twice daily). Twenty-four and 48 h after MCAO, neurological outcome (NO) was determined. Forty-eight h after MCAO, infarct volume by MRI, neuronal survival, inflammation factors and neurotrophin receptor (TrkB) were analysed. Stroke incidence was reduced, survival was prolonged and neurological outcome was improved in all treated SHR-SP with no differences between treated groups. In the acute intervention study, T and T+R, but not R alone, improved NO, reduced infarct volume, inflammation (TNFα), and induced TrkB receptor and neuronal survival in comparison to V. T, R or T+R had similar beneficial effects on stroke incidence and NO in hypertensive rats, confirming BP reduction as determinant factor in stroke prevention. In contrast, T and T+R provided superior neuroprotection in comparison to R alone in normotensive rats with induced cerebral ischemia.


Effectiveness of intensification therapies in Danes with Type 2 diabetes who use basal insulin: a population-based study.
To examine the usage and real-life effectiveness of intensification therapies in people with Type 2 diabetes treated with basal insulin. We used population-based healthcare databases in Denmark during 2000-2012 to identify all individuals with a first basal insulin prescription (with or without oral drugs), and evaluated subsequent intensification therapy with bolus insulin, premixed insulin or glucagon-like peptide-1 (GLP-1) receptor agonists. Poisson regression was used to compute the adjusted relative risks of reaching glycaemic control targets. We included 7034 initiators of basal insulin (median age 64 years, diabetes duration 5.3 years, 84% with oral co-medication and median (interquartile range) pre-insulin HbA1c level 77 (65-92) mmol/mol [9.2% (8.1-10.6%)]. Of these, 3076 (43.7%) received intensification therapy after a median of 11 months: 58.5% with premixed insulin, 29.0% with bolus insulin, 10.6% with GLP-1 receptor agonists, and 1.9% with more than one add-on. Overall, 22% had attained an HbA1c level of < 53 mmol/mol (< 7%) by 3-6 months after intensification, while 38% attained an HbA1c < 58 mmol/mol (< 7.5%). Compared with premixed insulin intensification, attainment of HbA1c < 53 and < 58 mmol/mol was similar with bolus insulin add-on [adjusted relative risk 1.03 (95% CI 0.86-1.24) and 1.02 (95% CI 0.91-1.15), and higher for GLP-1 receptor agonist add-on [adjusted relative risk 1.56 (95% CI 1.27-1.92) and 1.27 (1.10-1.47)]. Among people with Type 2 diabetes, 22 and 38% reached a target HbA1c < 53 mmol/mol (< 7%) or < 58 mmol/mol (< 7.5%), respectively, after intensification of their basal insulin therapy. Compared with premixed insulin, target attainment was similar with bolus insulin and higher with GLP-1 receptor agonists.


Typhus Group Rickettsiosis, Texas, USA, 2003-2013.
We characterized the epidemiology of typhus group rickettsiosis in Texas, USA. During 2003-2013, a total of 1,762 cases were reported to the state health department. The number of diagnosed cases and geographic expansion increased over time. Physician awareness is critical to diagnose and effectively treat rickettsial infections.


Maternal jail time, conviction, and arrest as predictors of children's 15-year antisocial outcomes in the context of a nurse home visiting program.
Data from the Nurse-Family Partnership intervention program were analyzed to compare the "selection" versus "unique" effects of maternal jail time on adolescent antisocial and health risk outcomes. Data from 320 women and their firstborn children were available from the prenatal, birth, and 15-year assessments. Consistent with a selection perspective, prenatal and demographic risks directly and indirectly related to many adolescent antisocial outcomes. Maternal conviction and arrest were also associated with adolescent contact with the criminal justice system and health risk behaviors. Maternal jail time predicted whether or not children had ever been stopped by police, sent to youth corrections, or run away from home. However, these associations were not significant after controlling for prenatal risk factors and maternal conviction and arrest. The results highlight the importance of maternal criminality and other risk factors in children's environments, including prenatal variables.


Elimination of fluconazole during continuous renal replacement therapy. An in vitro assessment.
Continuous renal replacement therapy (CRRT) efficiently eliminates fluconazole. However, the routes of elimination were not clarified. Adsorption of fluconazole by filters is a pending question. We studied the elimination of fluconazole in a model mimicking a session of CRRT in humans using the NeckEpur® model. Two filters were studied. The AV1000®-polysulfone filter with the Multifiltrate Pro. Fresenius and the ST150®-polyacrylonitrile filter with the Prismaflex. Baxter-Gambro were studied. Continuous filtration used a flowrate of 2.5 L/h in post-dilution only. Session were made in duplicate. Routes of elimination were assessed using the NeckEpur® model. The mean measured initial fluconazole concentration (mean ± SD) for the four sessions in the central compartment (CC) was 14.9 ± 0.2 mg/L. The amount eliminated from the CC at the end of 6 h-session at a 2.5 L/h filtration flowrate for the AV1000®-polysulfone and the ST150®-polyacrylonitrile filters were 90%-93% and 96%-94%, respectively; the clearances from the central compartment (CC) were 2.5-2.6 and 2.4-2.3 L/h, respectively. The means of the instantaneous sieving coefficient were 0.94%-0.91% and 0.99%-0.91%, respectively. The percentages of the amount eliminated from the CC by filtration/adsorption were 100/0%-95/5% and 100/0%-100/0%, respectively. Neither the ST150®-polyacrylonitrile nor the AV1000®-polysulfone filters result in any significant adsorption of fluconazole.


The Impact of the Novel Coronavirus Disease 2019 on Therapy Service Delivery for Children with Disabilities.
To assess the impact of the novel coronavirus disease 2019 (COVID-19) pandemic on the delivery of, and parent satisfaction with, therapy services for children with disabilities in early intervention, school, and outpatient settings. There were 207 parents of children with disabilities who completed a web-based survey about their child[ren]'s access to, and satisfaction with, therapy services during COVID-19. Parents also completed the Family-Provider Partnership Scale and the Telehealth Satisfaction Scale. Satisfaction was compared between families receiving therapies in school, early intervention, outpatient, and multiple settings. Forty-four percent of parents reported low satisfaction with their child[ren]'s therapy services during the pandemic. Access to telehealth positively predicted overall satisfaction and satisfaction with the family-provider partnership, whereas receiving school-based therapies negatively predicted overall satisfaction and satisfaction with the family-provider partnership. School-based therapies are legally mandated for eligible students, free of cost to families, integrated in the academic setting, and less burdensome on parents than other services. Thus, given the disparity in parental satisfaction regarding school-based service delivery, addressing therapy delivery in school-based settings during the duration of COVID-19 is critical for preventing increased disparities and more effectively meeting children's needs. Telehealth seems to be a promising option for continuing high-quality services during the duration of the COVID-19 pandemic and for families who face barriers in accessing services in general. Future studies are warranted with larger and more diverse samples, as well as longitudinal studies that monitor service access and parent satisfaction throughout the remainder of the pandemic.


Freeze-Dried Royal Jelly Proteins Enhanced the Testicular Development and Spermatogenesis in Pubescent Male Mice.
Spermatogenesis and hormones secretions are crucial endocrine and physiological process for maintaining the life. Royal Jelly (RJ) bioactive components are Major Royal Jelly Proteins (MRJPs), owing exceptional biological properties. However, the effects of RJ on pup's testicular development during neonatal and pubertal period exposure hasn't been adequately studied. The aim of the study was to detect neonatal sexual hormones concentration and histopathological changes on testicular development of the male progeny after oral exposure to freeze-dried RJ for 35 consecutive days. After mice give birth, male pups were collected together, separated by sex, and randomly standardized to seven (7) male pups per dam. Male pups were assigned to control diet (CON group), low dose RJ (L-RJ group) diet (control diet + 125 mg/kg/day RJ), moderate dose RJ (M-RJ group) diet (control diet + 250 mg/kg/day RJ) and high dose of RJ (H-RJ group) diet (control diet + 500 mg/kg/day RJ). After weaning, male pups were continuously fed with freeze-dried RJ until the age of PNDs 35. The results revealed that, oral M-RJ (250 mg/kg/day) administration significantly (p < 0.05) increased the testis weight, the diameter of seminiferous tubule and the height of seminiferous epithelium of offspring mice at PNDs 14. However, high-dose RJ (500 mg/kg/day) decreased the diameter of seminiferous tubule but increased the height of seminiferous epithelium of male offspring (p < 0.05) at the same time point. Furthermore, oral M-RJ treatment significantly (p < 0.05) increased the testis weight and spermatogenesis at PNDs 21. Whereas, oral H-RJ treatment significantly (p < 0.05) reduced the diameter of seminiferous tubule and the height of seminiferous epithelium at PNDs 21. At PNDs 35, oral M-RJ treatment increased the testis weight, the diameter of seminiferous tubule and the level of FSH. While, high-dose of RJ reduced testis weight and size (diameter of seminiferous tubule and height of seminiferous epithelium), ratio of apoptotic germ cells and incomplete spermatogenesis collectively. In addition, sexual hormone secretions (FSH, LH, E2) were decreased after RJs treatment (L-RJ, M-RJ, H-RJ) at PNDs 21 respectively. In conclusion, the results concluded that oral administration of low and moderate doses of RJ could enhance the development of testis at neonate period until pubescent, whereas unfavorable adverse effects induced by high dose of RJ might remain.


Nitrogen depletion causes up-regulation of glutathione content and gamma-glutamyltranspeptidase in Schizosaccharomyces pombe.
This work aims to elucidate the relationship between nitrogen depletion and Glutathione (GSH) level in Schizosaccharomyces pombe. The total GSH level was much higher in the Pap1-positive KP1 cells than in the Pap1-negative TP108-3C cells, suggesting that synthesis of GSH is dependent on Pap1. When the Pap1-positive KP1 cells were transferred to the nitrogen-depleted medium, total GSH level significantly increased up to 6 h and then slightly declined after 9 h. Elevation of the total GSH level was observed to be much less with the Pap1-negative cells. However, glucose deprivation was not able to enhance the GSH level in the KP1 cells. Activity of gamma-glutamyltranspeptidase (gamma-GT), an enzyme in the first step of GSH catabolism, also increased during nitrogen depletion. The total GSH level was more significantly enhanced in the KP1 cells overexpressing gamma-GT2 than gamma-GT1 during nitrogen starvation. Reactive oxygen species (ROS) levels were not changed during nitrogen starvation in both Pap1-positive and Pap1-negative cells. Collectively, nitrogen depletion causes up-regulation of GSH synthesis and gamma-GT in a Pap1-dependent manner.


Remarks on "Reply to the responses to the comments on "uncertainty profiles for the validation of analytical methods" by Saffaj and Ihssane".
This letter provides an opportunity to expand further on the problems associated with using tolerance interval for share validated analytical methods and to estimate the measurement uncertainty. Indeed, we propose at clarifying points that have been raised by Rozet et al. (Talanta 100 (2012) 290-292) as some of them merit to be discussed. In that respect, we demonstrate here that β-content, γ-confidence tolerance intervals will provide perfect estimates of the routine uncertainty. In particular, we confirm that there is "no statistically significant difference" between the uncertainties estimated by our methodology with those obtained from the routine phase. Obviously, this is an opportunity to show which of the two types of tolerance interval i.e., β-expectation tolerance interval or β-content, γ-confidence tolerance interval allows a perfect estimate of the routine uncertainty. Furthermore, we prove that the β-expectation tolerance interval does not provide an adequate balance between consumer risk and producer risk.


Deaths associated with electric shock injuries in children and adults: A 10-year retrospective examination in Şanlıurfa, Southeast Turkey (2012-2022).
Electric shock injuries (EIs) have high rates of morbidity and mortality in both children and adults. The aim of this study was to examine autopsy cases resulting from EIs and to compare pediatric and adult groups with respect to sociodemographic data, clinical characteristics, location of the incident, electricity entry-exit wound characteristics, current direction, pathological effects of the electric shocks on the body, and cause of death. A total of 8075 autopsies conducted between 2012 and 2022 were retrospectively examined. Şanliurfa is a city in the southeast of Turkey with the highest birth rate in the country. Of 123 cases of death resulting from EIs in Şanliurfa, 58 (47.2%) were children (age < 18 years). In the majority of children (81%), a low-voltage injury resulted from a domestic appliance while the children were playing at home in a rural area. In the vast majority of adults, a high-voltage injury (HVI) resulted from a workplace accident due to working with HVI materials in an area outside the home. The manner of death was accidental in all the electric shock injuries. The electricity entry and exit wounds formed as a result of EIs had similar characteristics in both children and adults, with no significant difference identified. In the province of Şanliurfa, Turkey, which borders Syria and where the main occupation is agricultural activities, there is a need to increase electrical safety precautions within the home, educate parents, and increase electrical safety conditions and worker education in the workplace.


Enantiomeric separation of alanyl and leucyl dipeptides by capillary electrophoresis with cyclodextrins as chiral selectors.
Eight neutral cyclodextrins were tested for the enantiomeric separation of alanyl and leucyl dipeptides by capillary electrophoresis at pH 3, and seven out of the eight cyclodextrins proved suitable for the separation of one or more of the dipeptide enantiomer pairs. The best results were obtained with heptakis(2,6-di-O-methyl)-beta-cyclodextrin. The dipeptides that were separated were mainly the aromatic and the more lipophilic aliphatic dipeptides. Mobility difference plots at pH 3.0 with malonic acid-triethanolamine as background electrolyte showed that the aromatic dipeptides had higher affinities for the cyclodextrin than the nonpolar, aliphatic dipeptides. The results suggested that, under the conditions applied, the C-terminal amino acid rather than the N-terminal one is involved in the chiral discrimination.


Cloning and characterization of a pentatricopeptide protein encoding gene (LOJ) that is specifically expressed in lateral organ junctions in Arabidopsis thaliana.
A line exhibiting expression of beta-glucuronidase (GUS) in the lateral organ junctions and shoot apical meristem (SAM) was identified from a population of T-DNA tagged lines carrying a promoter-less GUS gene. Southern hybridization confirmed the presence of a single T-DNA insertion in this line. The plant sequences flanking the T-DNA were cloned by TAIL PCR and sequenced. The insertion of T-DNA was found to be in the upstream region of a hypothetical gene (At2g39230). This gene, which we term as LOJ to indicate its specific expression in all lateral organ junctions encodes a predicted protein containing pentatricopeptide (PPR) motifs. This gene appears to belong to a group of TATA-less promoters and codes for a long ORF without any intron. The gene apparently codes for a protein of 97.65 kD with a mitochondrial target sequence at the N-terminal. Transcript analysis revealed that the expression of the gene is specifically restricted to the lateral organ junctions throughout the life of the plants. 5' RACE analysis revealed a 95 nucleotide long UTR region for this hypothetical gene. In silico analysis of the upstream region failed to identify a TATA box within -146 nucleotides. GUS expression analysis of the line 149 and the transgenic plants generated with constructs carrying the upstream sequences of this gene fused to uidA identified that the specificity of the expression of this gene resides within -569 to -152 bp region. The specific expression of LOJ at the base of lateral organ and shoot apical meristem (SAM) suggests an important role of LOJ in lateral organ development and boundary demarcation.


An outcome study of patient-controlled morphine analgesia, with or without ketorolac, following radical retropubic prostatectomy.
We compared the effects of postoperative pain control strategies on recovery after radical retropubic prostatectomy. The results in 22 consecutive patients who underwent radical retropubic prostatectomy between 1993 and 1994 were evaluated. Pain control was achieved using morphine patient-controlled analgesia in 11 patients or nonsteroidal anti-inflammatory ketorolac in 11. Outcome measures were compared between the 2 groups. The interval to return of bowel function, length of hospitalization and total hospital costs were significantly decreased in the ketorolac treated patients. Pain control with ketorolac affords excellent analgesia while allowing for earlier recovery of bowel function, shorter hospitalization and lower overall costs in patients undergoing radical retropubic prostatectomy.


Treatment of severe IgA nephropathy in children.
We treated ten children with severe IgA nephropathy (IgAN) [proteinuria greater than 1 g/day, hypertension, renal insufficiency, segmental sclerosis, crescent formation and/or glomerular basement membrane (GBM) deposition of IgA] with prednisone and azathioprine for 1 year. Following the year of therapy, seven of the ten children underwent a repeat kidney biopsy. All biopsies were scored for activity (percentage of glomeruli demonstrating crescent formation, degree of mesangial proliferation and interstitial infiltrate; maximum score = 9) and chronicity (percentage of glomeruli demonstrating fibrous crescents, segmental sclerosis, global sclerosis, and degree of tubular atrophy and interstitial fibrosis; maximum score = 12). After 1 year of therapy, the protein excretion of all the children decreased significantly (P less than 0.01) from 4,052 +/- 3,190 mg/day to 1,692 +/- 1,634 mg/day. The activity score decreased significantly (P less than 0.01) from 4.35 +/- 0.94 prior to therapy to 2.28 +/- 0.75 after therapy while the chronicity score was unchanged (5.42 +/- 1.7 vs 5.85 +/- 2.0). The percentage of glomeruli demonstrating cellular crescents decreased (P less than 0.05) from 21.2 +/- 21.7% prior to therapy to 0.94 +/- 2.4% after therapy. Mesangial deposition of IgA persisted but GBM deposition of IgA was less prominent after therapy. During the follow-up period (mean 2.6 years, range 9 months-7.5 years), one child required brief retreatment for biopsy-confirmed recurrence of active disease, two children have developed renal insufficiency due to progressive scarring in the absence of inflammation, while the remaining seven are stable. We suggest that treatment with prednisone and azathioprine may be beneficial in children with severe IgAN and that a controlled clinical trial is warranted.


Study of the precursors of ovine lactoproteins: primary structures of the 'signals' and enzymic processing of prelactoproteins by mammary microsomal membranes.
The radiolabelled primary translation products of ovine mammary mRNAs synthesized in a wheat germ cell-free system were isolated by immunoprecipitation and analysed by automated Edman degradation. The 3 'Ca-sensitive' caseins (alpha S1, alpha S2 and beta), kappa-casein, beta-lactoglobulin and alpha-lactalbumin were found to be synthesized as precursors with amino terminal extensions of 15, 21, 18 and 19 amino acid residues respectively. The extra pieces of these various lactoproteins are similar to 'signal' peptides of other secretory proteins in their length and hydrophobicity. The occurrence of an alanyl residue at the C-termini of the extra pieces of the 6 ovine prelactoproteins suggests that the mammary proteinase responsible for the cleavage of the signal peptides may have an elastase-like specificity. When mammary mRNAs were translated in a wheat germ cell-free system in the presence of mammary microsomal membranes, pre-beta-casein was converted into authentic beta-casein as demonstrated by amino terminal sequence analyses. Additionally, pre-beta-casein was post-translationally converted into authentic beta-casein by a specific proteinase(s) extracted from rough microsomes with Na deoxycholate.


5-HT2A receptor gene polymorphism and negative symptoms in first episode (drug-naive) Chinese Han nationality individuals with schizophrenia.
To investigate whether the 5-hydroxytryptamine 2A receptor (5-HT2A) gene T102C polymorphism is associated with the severity symptoms and negative symptoms in the first episode Chinese Han nationality patients with schizophrenia. Altogether 201 first episode Chinese Han nationality patients with schizophrenia were enrolled in this study. Genotyping of 5-HT2A gene T102C polymorphism was performed by PCR-RFLP technique. The positive and negative Symptom Scale (PANSS) was used for the evaluation of the severity of psychotic symptoms before any drug treatment. 5-HT2A receptor 102-T/T genotype was significantly associated with both the PANSS total and negative symptom subscale baseline scores before the treatment, but not with the positive and general psychopathology subscales. 5-HT2A T102C functional polymorphism may play a role in negative symptoms and prognosis of Chinese Han nationality people with schizophrenia.


Factors influencing algal consumption and feeding rate in Heterotrissocladius changi Saether and Polypedilum nebeculosum (Meigen) (Chironomidae: Diptera).
Factors influencing the consumption of algae and the rate of feeding by the larvae of Heterotrissocladius changi Saether and Polypedilum nebeculosum (Meigen) (Chironomidae: Diptera) were determined from collections made between July 1975 and May 1977 in Yellowknife Bay, situated in the Canadian subarctic. Although both species fed heavily on algae during the summer, few cells were ingested in the winter, coincident with an overall reduction in feeding intensity. H. changi fed primarily on benthic species (Achnanthes minutissima, Achnanthes pinnata, Fragilaria pinnata, Fragilaria vaucheriae, Navicula spp., Scenedesmus spp.) Whereas P. nebeculosum was restricted to planktonic forms (Dinobryon spp., Scenedesmus spp.). The consumption of algae by H. changi depended largely on the density of the microflora in the environment. This factor had little influence on P. nebeculosum and was replaced by size selection, which prevented the ingestion of many planktonic algal species. The importance of algae to both chironomids also depended on the susceptability of certain algal forms to digestion. Temperature generally regulated the intensity of feeding of both H. changi and P. nebeculosum. However, changing day-length initiated heavy feeding during April and May, despite low water temperatures. The depth of water and the organic content of the substrate had no detectable effect on the amount of material in the guts.


Effects of simulated acid rain on the morphology, phenology and dry biomass of a local variety of maize (Suwan-1) in Southwestern Nigeria.
Effects of acid rain on the morphology, phenology and dry biomass of maize (Suwan-1 variety) were investigated. The maize seedlings were subjected to different pH treatments (1.0, 2.0, 3.0, 4.0, 5.0 and 6.0) of simulated acid rain (SAR) with pH 7.0 as the control for a period of 90 days. The common morphological defects due to SAR application were necrosis and chlorosis. It was observed that necrosis increased in severity as the acidity increased whilst chlorosis was dominant as the acidity decreased. SAR encouraged rapid floral and cob growth but with the consequence of poor floral and cob development in pH 1.0 to 3.0 treatments. The result for the dry biomass indicates that pH treatments 2.0 to 7.0 for total plant biomass were not significantly different (P > 0.05) from one another, but were all significantly higher (P < 0.05) than pH 1.0. Therefore, it may be deduced that Suwan-1 has the potential to withstand acid rain but with pronounced morphological and phenological defects which, however, have the capacity to reduce drastically the market value of the crop. Therefore, it may be concluded that Suwan-1 tolerated acid rain in terms of the parameters studied at pH 4.0 to 7.0 which makes it a suitable crop in acid rain-stricken climes. This research could also serve as a good reference for further SAR studies on maize or other important cereals.


QRS subtraction for atrial electrograms: flat, linear and spline interpolations.
The main objective of this article is to implement and compare QRS subtraction techniques for intra-cardiac atrial electrograms based on using the surface ECG as a reference. A band-pass filter between 8 and 20 Hz followed by rectification, and then a low-pass filter at 6 Hz are used for QRS detection. QRS subtraction was performed using three different approaches: flat, linear and spline interpolations. QRS subtraction affects the power of the signals but it normally does not affect the dominant frequency. The average power of the atrial electrograms after QRS subtraction is significantly reduced for frequencies above 10 Hz.


Breastfeeding in Prevention of Postpartum Acute Pancreatitis.
Acute pancreatitis (AP) caused by gallstones has an increased rate of incidence in young women in the 2 years postpartum. Middle-aged women with longer periods of breastfeeding have less hospitalization for gallbladder disease. To investigate whether breastfeeding or other variables may be associated with AP. We conducted a population-based case-control study among all Sicilian women of childbearing age, and we identified all women who delivered (2013-2016) and had AP within 2 years postpartum. We reviewed their medical records, and for each case we matched four women of the same age (± 5 years), without AP. Univariate and multivariate logistic regression was used to estimate the odds ratios (OR) with their confidence intervals (CI) to assess associations between AP and clinical determinants. In the 74 women with AP and 298 controls at univariate analysis, > 6 months oral contraception history (p < 0.01; OR 3.30; 95% CI 1.33-8.16), previous biliary disease (p < 0.001; OR 5.90; 95% CI 1.98-17.57) and smoking (p = 0.035; OR 2.04; 95% CI 1.04-4.0) were predictors of AP; amenorrhea ≥ 3 months (p < 0.001; OR 0.34; 95% CI 0.19-0.59) and breastfeeding ≥ 3 months (p < 0.001; OR 0.07; 95% CI 0.03-0.14) were protective. At multivariate analysis, previous biliary disease (p = 0.011; OR 5.49; 95% CI 1.48-20.38) and breastfeeding ≥ 3 months (p < 0.001; OR 0.06; CI 95% 0.03-0.14) were associated with AP. Women who breastfeed for at least 3 months and do not have a history of biliary disorders have reduced risk of developing AP in the 2 years after delivery.