Long-term effects of THC exposure on reward learning and motivated behavior in adolescent and adult male rats.
The endocannabinoid system makes critical contributions to reward processing, motivation, and behavioral control. Repeated exposure to THC or other cannabinoid drugs can cause persistent adaptions in the endocannabinoid system and associated neural circuitry. It remains unclear how such treatments affect the way rewards are processed and pursued. We examined if repeated THC exposure (5 mg/kg/day for 14 days) during adolescence or adulthood led to long-term changes in rats' capacity to flexibly encode and use action-outcome associations for goal-directed decision making. Effects on hedonic feeding and progressive ratio responding were also assessed. THC exposure had no effect on rats' ability to flexibly select actions following reward devaluation. However, instrumental contingency degradation learning, which involves avoiding an action that is unnecessary for reward delivery, was augmented in rats with a history of adult but not adolescent THC exposure. THC-exposed rats also displayed more vigorous instrumental behavior in this study, suggesting a motivational enhancement. A separate experiment found that while THC exposure had no effect on hedonic feeding behavior, it increased rats' willingness to work for food on a progressive ratio schedule, an effect that was more pronounced when THC was administered to adults. Adolescent and adult THC exposure had opposing effects on the CB1 receptor dependence of progressive ratio performance, decreasing and increasing sensitivity to rimonabant-induced behavioral suppression, respectively. Our findings reveal that exposure to a translationally relevant THC exposure regimen induces long-lasting, age-dependent alterations in cognitive and motivational processes that regulate the pursuit of rewards.


Genotypic and phenotypic characterization of G6PD deficiency in Bengali adults with severe and uncomplicated malaria.
Control of malaria increasingly involves administration of 8-aminoquinolines, with accompanying risk of haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Few data on the prevalence and genotypic basis of G6PD deficiency are available from Bangladesh, where malaria remains a major problem in the South (Chittagong Division). The aim of this study was to determine the prevalence of G6PD deficiency, and associated G6PD genotypes, in adults with falciparum malaria in southern Bangladesh. G6PD status was assessed via a combination of fluorescent spot testing (FST) and genotyping in 141 Bengali patients admitted with falciparum malaria to two centres in Chittagong Division from 2012 to 2014. In addition, an analysis of genomic data from 1000 Genomes Project was carried out among five healthy Indian subcontinent populations. One male patient with uncomplicated malaria was found to have G6PD deficiency on FST and a genotype associated with deficiency (hemizygous Orissa variant). In addition, there were two female patients heterozygous for deficiency variants (Orissa and Kerala-Kalyan). These three patients had a relatively long duration of symptoms prior to admission compared to G6PD normal cases, possibly suggesting an interaction with parasite multiplication rate. In addition, one of 27 healthy local controls was deficient on FST and hemizygous for the Mahidol variant of G6PD deficiency. Examination of 1000 Genomes Project sequencing data across the Indian subcontinent showed that 19/723 chromosomes (2.63%) carried a variant associated with deficiency. In the Bengali from Bangladesh 1000 Genomes population, three of 130 chromosomes (2.31%) carried deficient alleles; this included single chromosomes carrying the Kerala-Kalyan and Orissa variants. In line with other recent work, G6PD deficiency is uncommon in Bengalis in Bangladesh. Further studies of particular ethnic groups are needed to evaluate the potential risk of wide deployment of primaquine in malaria control efforts in Bangladesh.


[Gastrointestinal Stromal Tumour (GIST). Case report].
In 1987 a 73 year old man was diagnosed with a malignant sarcoma of the anus. It was originally regarded as a leiomyosarcoma. Fourteen years later the original diagnoses of the specimen was reviewed and the diagnosis was changed to GIST (gastrointestinal stromal tumour). This diagnosis was confirmed with appropriate immunohistochemical staining on the tumour tissue. This is the first case of GIST in the anus diagnosed in Iceland.


A Short-Term Time-Series Data Analysis Algorithm for Flavor Release during the Start of Eating.
"Retronasal aroma" refers to the aroma released from food during consumption and traveling through the nose after leaving the mouth. It is closely related to the behavior of odor compounds released from food into the mouth and plays a crucial role in our overall perception of flavor. As a result, research focusing on measuring the behavior of retronasal aroma has gained attention for exploring the relationship between sensory perception and flavor. We attempted to develop a data analysis method that specifically targets a time span of a few seconds to tens of seconds, starting from when food is placed in the mouth during eating and extending to just after swallowing. In this study, we observed a strong correlation between the periodic waveform data derived from performing the third derivative (jerk) on the detection intensity data obtained using a mass spectrometer and the behavior of the detection intensity. Furthermore, by performing a frequency analysis using a fast Fourier transform on the jerk data, it was possible to extract the frequencies that contribute to sensory perception during eating. Furthermore, the reconstructed jerk data derived from the extracted data using the inverse fast Fourier transform provided a clearer explanation of sensory perception during eating. Our algorithm suggests new short-term time-series data applications.


Cytomegalovirus Esophagitis in an Immunocompromised Patient.
Cytomegalovirus (CMV) can present with end-organ disease (EOD), particularly in patients with a CD4 cell count <50/mm3. While EOD in immunocompromised patients commonly presents as CMV retinitis (30%) and CMV colitis (5-10%), CMV esophagitis is rare. CMV is the third most common infectious esophagitis following Candida and Herpes Simplex. CMV esophagitis presents with odynophagia, dysphagia, and abdominal pain. Endoscopic exam may reveal large, linear distal esophageal ulcers. Histopathology or serology studies are diagnostic, though serology may be unreliable in the extremely immunosuppressed. Current treatment consists of antivirals such as ganciclovir and valganciclovir. Esophageal disease due to CMV carries a poor prognosis in the immunocompromised. We present the case of a 56-year-old male with a medical history of HIV/AIDS and stage III rectal squamous cell cancer who presented with shortness of breath, weakness, and chronic diarrhea. His HIV was previously well-controlled on antiretroviral therapy. However, due to his malignancy, he was undergoing treatment with chemotherapy and radiation. Initial labs revealed a CD4 count of 42. His clinical course consisted of Escherichia coli septicemia, new-onset atrial fibrillation with a rapid ventricular response, worsening pneumonia, possible metastasis, progressive diarrhea, and potential oropharyngeal candidiasis. Despite several broad-spectrum antimicrobial regimens, he remained symptomatic with new complaints of dysphagia and odynophagia. Eventually, the appearance of vesicular lesions on the lips and a repeat CD4 count of 13 garnered a suspicion of HSV or CMV. This complicated case highlights the necessity for a high index of suspicion of rare manifestations of CMV EOD in an immunocompromised patient presenting with confounding clinical symptoms and extensive diagnoses.


Application of transcriptome in time analysis and donor characterization in blood samples.
As an effective supplement to the current forensic DNA typing and one of the research hotpots in forensic science, the in-depth mining and characterization of biological evidence can provide rich and reliable clues for case investigation. In this study, the time-dependent variations of transcriptome were confirmed in in vitro blood samples within 0-168 days and a random forest model was established to realize the classification of blood samples with different TSD (time since deposition). Meanwhile, significant differences were observed in the transcripts of blood samples with different smoking habits and genders within a certain time period. HLA-DRB1, HLA-DQB1 and HLA-DQA2 were identified as markers for smoking habit identification, while the transcripts for RPS4Y1 and EIF1AY from the non-recombining region of the Y chromosome (NRY) were identified as markers for male sex identification. Thus, this study provides a theoretical foundation and experimental strategy for establishing a transcriptome-based method for characterizing blood sample retention time and donor characteristics in the field of forensic investigation.


CCR6-dependent positioning of memory B cells is essential for their ability to mount a recall response to antigen.
Chemokine-dependent localization of specific B cell subsets within the immune microarchitecture is essential to ensure successful cognate interactions. Although cognate interactions between T cells and memory B cells (B(mem)) are essential for the secondary humoral immune responses, the chemokine response patterns of B(mem) cells are largely unknown. In contrast to naive B cells, this study shows that Ag-specific B(mem) cells have heightened expression of CCR6 and a selective chemotactic response to the CCR6 ligand, CCL20. Although CCR6 appears be nonessential for the initial clonal expansion and maintenance of B(mem), CCR6 is essential for the ability of B(mem) to respond to a recall response to their cognate Ag. This dependency was deemed intrinsic by studies in CCR6-deficient mice and in bone marrow chimeric mice where CCR6 deficiency was limited to the B cell lineage. Finally, the mis-positioning of CCR6-deficient B(mem) was revealed by immunohistological analysis with an altered distribution of CCR6-deficient B(mem) from the marginal and perifollicular to the follicular/germinal center area.


The work environment and empowerment as predictors of patient safety culture in Turkey.
As scant research based information is available regarding the work environment, empowerment and patient safety culture, this study from a developing country (Turkey) in which health care institutions are in a state of transition, aimed to investigate further the relationships between these three variables. A cross-sectional descriptive design was employed. The sample comprised 274 nurse participants working in a university hospital located in Izmir (Turkey). In data evaluation, descriptive statistics and hierarchical regression analyses were applied. The work environment and structural empowerment were related to the patient safety culture and explained 55% of the variance in patient safety culture perceptions. 'Support for optimal patient care', 'nurse/physician relationships' and 'staff involvement in organisational affairs' were the significant predictors. An enhancement of the work environment and providing access to empowerment structures may help health care organisations improve the patient safety culture. In light of the findings, the following actions can be recommended to inform health care leaders: providing necessary resources for nursing practise, encouraging nurses' participation in decision-making, strengthening communication within the team and giving nurses the opportunities to cope with challenging work problems to learn and grow.


Development of a fidelity measure for community integration programmes for people with acquired brain injury.
The paper describes development of the Assessment of Community Integration Programme Attributes (ACIPA) measure based on a descriptive community integration framework. The purpose of this measure is to allow evaluation of community integration programmes for adults with acquired brain injury (ABI). The Community Integration Framework (CIF) was used to design a fidelity evaluation measure through consultation with 37 participants from five stakeholder groups (practitioners, researchers, policy-makers, people with ABI and family members of people with ABI) using semi-structured interviews, focus groups, iterative surveys and a multi-attribute utility (MAU) method. The resultant measure included seven themes and 21 attributes. Each attribute included indicators and probing questions. Weights were assigned to each theme and constituent attributes. Programme evaluation commonly focuses on outcomes, often overlooking analysis of programme processes. Although it requires further psychometric (reliability and validity) development, the Assessment of Community Integration Programme Attributes may be used to assess the relationship between programme processes and specific outcomes and also to inform the development of programmes aiming to enhance community integration for adults with ABI.


Implementing Clinical Prediction Models: Pushing the Needle Towards Precision Pharmacotherapy.
Clinical prediction models promise a future of precision drug therapy. However, very few models are used in practice. Although models can eliminate unwanted clinical guesswork, several barriers hinder model implementation in practice. Here we discuss the less well-recognized barriers hindering model implementation for precision prescribing, highlighting areas that warrant attention, primarily relating to ethical and regulatory considerations that are requisite in paving the way towards a future of precision pharmacotherapy.


Atoltivimab/maftivimab/odesivimab (Inmazeb) combination to treat infection caused by Zaire ebolavirus.
Zaire ebolavirus has been responsible for several catastrophic outbreaks with a high mortality rate. Unfortunately, there were no approved therapies or vaccines to treat or prevent infections caused by Ebola virus (EBOV) or other filoviruses. Atoltivimab/ maftivimab/odesivimab (Inmazeb) is the first Food and Drug Administration (FDA)-approved treatment for Zaire ebolavirus infection in adult and pediatric patients, including neonates born to a mother who is reverse transcription polymerase chain reaction (RT-PCR)-positive for Zaire ebolavirus infection. The efficacy of Inmazeb has been established in vivo and it has successfully completed a phase I clinical trial in healthy individuals with no drug-related adverse effects. Additionally, Inmazeb has displayed significant reduction in mortality in the PALM (PAmoja tuLinde Maisha) trial, when compared with the control arm receiving ZMapp. Inmazeb has received orphan drug designation from both the U.S. FDA and the European Medicines Agency (EMA).


Multiplexed Fluorescent Immunohistochemical Staining of Four Endometrial Immune Cell Types in Recurrent Miscarriage.
Immunohistochemistry is the most commonly used method for the identification and visualization of tissue antigens in biological research and clinical diagnostics. It can be used to characterize various biological processes or pathologies, such as wound-healing, immune response, tissue rejection, and tissue-biomaterial interactions. However, the visualization and quantification of multiple antigens (especially for immune cells) in a single tissue section using conventional immunohistochemical (IHC) staining remains unsatisfactory. Hence, multiplexed technologies were introduced in recent years to identify multiple biological markers in a single tissue sample or an ensemble of different tissue samples. These technologies can be especially useful in differentiating the changes in immune cell-to-cell interactions within the endometrium between fertile women and women with recurrent miscarriages during implantation. This paper describes a detailed protocol for multiplexed fluorescence IHC staining to investigate the density and clustering of four major immune cell types simultaneously in precisely timed endometrial specimens during embryo implantation. The method includes sample preparation, multiplex optimization with markers for immune cell subtypes, and the scanning of the slides, followed by data analysis, with specific reference to detecting endometrial immune cells. Using this method, the density and clustering of four major immune cell types in the endometrium can be simultaneously analyzed in a single tissue section. In addition, this paper will discuss the critical factors and troubleshooting to overcome possible fluorophore interference between the fluorescent probes being applied. Importantly, the results from this multiplex staining technique can help provide an in-depth understanding of the immunologic interaction and regulation during embryo implantation.


Recent syncope and unexplained falls are associated with poor cognitive performance.
To compare cognitive performance in participants with and without syncope and unexplained falls in a large population representative sample aged 50 years or older. Participants of the Irish longitudinal study on ageing (TILDA) were studied. Participants with a history of syncope and/or unexplained falls in the past 12 months were compared with those with no reported events. Cognitive performance was measured using the Montreal cognitive assessment (MoCA) score. Multivariate linear regression analysis controlling for potential confounders was performed to compare cognitive function by syncope and falls status. Five thousand eight hundred and forty-six participants were analysed, median age 62 years (inter-quartile range=14), and 54% were female. Five hundred and forty-nine (9.4%) had a syncopal event and/or an unexplained fall in past 12 months. One hundred and two (1.8%) subjects had two-plus syncopal events in the same period. There was a significant association between syncope/falls history and lower MoCA score, following adjustment for all confounders (B=-0.4; -0.69, -0.11; P=0.006). Higher syncope burden was also associated with lower performance; however, this was largely explained by confounders. There was no age interaction with these findings. Participants who experienced syncope and/or non-accidental falls in the previous year have poor global cognitive performance compared with case-controls. There was no effect of age on our results. Further investigation of the association between syncope burden, unexplained falls and cognitive decline is required to establish a relationship between these disorders.


Synchronous Hepatoblastoma and Neuroblastoma in Two Chinese Infants.
Background: Commonly, pediatric solid tumors occur independently. Only two patients with synchronous hepatoblastoma (HBL) and neuroblastoma (NBL) have been reported. Case reports: Two Chinese infants presented with abdominal mass at 10 and 8 months. Computed tomography (CT) scans in both revealed hepatic masses with additional mediastinal or adrenal masses. Pathology confirmed synchronous HBLs in the liver and NBLs in the mediastinum and adrenal. Next generation sequencing (NGS) found no remarkable germline mutations. Both patients received gross total resections with chemotherapy before or after surgery. They were followed up for 36 and 8 months, and recovered well. Conclusion: These two cases of synchronous HBL and NBL tumors lacked significant genetic alterations.


Three-Dimensional Neural Spheroid Culture: An In Vitro Model for Cortical Studies.
There is a high demand for in vitro models of the central nervous system (CNS) to study neurological disorders, injuries, toxicity, and drug efficacy. Three-dimensional (3D) in vitro models can bridge the gap between traditional two-dimensional culture and animal models because they present an in vivo-like microenvironment in a tailorable experimental platform. Within the expanding variety of sophisticated 3D cultures, scaffold-free, self-assembled spheroid culture avoids the introduction of foreign materials and preserves the native cell populations and extracellular matrix types. In this study, we generated 3D spheroids with primary postnatal rat cortical cells using an accessible, size-controlled, reproducible, and cost-effective method. Neurons and glia formed laminin-containing 3D networks within the spheroids. The neurons were electrically active and formed circuitry through both excitatory and inhibitory synapses. The mechanical properties of the spheroids were in the range of brain tissue. These in vivo-like features of 3D cortical spheroids provide the potential for relevant and translatable investigations of the CNS in vitro.


Elemental fingerprint as a cerebrospinal fluid biomarker for the diagnosis of Parkinson's disease.
The diagnosis of Parkinson's disease (PD) still lacks objective diagnostic markers independent of clinical criteria. Cerebrospinal fluid (CSF) samples from 36 PD and 42 age-matched control patients were subjected to inductively coupled plasma-sector field mass spectrometry and a total of 28 different elements were quantified. Different machine learning algorithms were applied to the dataset to identify a discriminating set of elements yielding a novel biomarker signature. Using 19 stably detected elements, the extreme gradient tree boosting model showed the best performance in the discrimination of PD and control patients with high specificity and sensitivity (78.6% and 83.3%, respectively), re-classifying the training data to 100%. The 10 times 10-fold cross-validation yielded a good area under the receiver operating characteristic curve of 0.83. Arsenic, magnesium, and selenium all showed significantly higher mean CSF levels in the PD group compared to the control group (p = 0.01, p = 0.04, and p = 0.03). Reducing the number of elements to a discriminating minimum, we identified an elemental cluster (Se, Fe, As, Ni, Mg, Sr), which most importantly contributed to the sample discrimination. Selenium was identified as the element with the highest impact within this cluster directly followed by iron. After prospective validation, this elemental fingerprint in the CSF could have the potential to be used as independent biomarker for the diagnosis of PD. Next to their value as a biomarker, these data also argue for a prominent role of these highly discriminating six elements in the pathogenesis of PD.


Transfer of ochratoxin A into tea and coffee beverages.
Ochratoxin A (OTA) is nephrotoxic, hepatotoxic, immunotoxic, neurotoxic, reprotoxic, teratogenic, and carcinogenic (group 2B), being characterized by species and sex differences in sensitivity. Despite the fact that OTA is in some aspects a controversial topic, OTA is the most powerful renal carcinogen. The aim of this study was to make a small survey concerning OTA content in black tea, fruit tea, and ground roasted coffee, and to assess OTA transfer into beverages. OTA content was measured using a validated and accredited HPLC-FLD method with a limit of quantification (LOQ) of 0.35 ng/g. The OTA amount ranged from LOQ up to 250 ng/g in black tea and up to 104 ng/g in fruit tea. Black tea and fruit tea, naturally contaminated, were used to prepare tea infusions. The transfer from black tea to the infusion was 34.8% ± 1.3% and from fruit tea 4.1% ± 0.2%. Ground roasted coffee naturally contaminated at 0.92 ng/g was used to prepare seven kinds of coffee beverages. Depending on the type of process used, OTA transfer into coffee ranged from 22.3% to 66.1%. OTA intakes from fruit and black tea or coffee represent a non-negligible human source.


A randomized phase II study of sequential docetaxel and doxorubicin/cyclophosphamide in patients with metastatic breast cancer.
Docetaxel has yielded promising response rates as a component of doxorubicin-based combination schedules in patients with metastatic breast cancer, including docetaxel/doxorubicin and docetaxel/doxorubicin/cyclophosphamide (AC). This randomized two-stage phase II study was conducted to evaluate sequential treatment with docetaxel and AC as first-line treatment in patients with recurrent or metastatic breast cancer previously untreated with chemotherapy for metastatic disease. Thirty-three patients were randomized to either docetaxel (100 mg/m(2)) on day 1 of a 21-day cycle for three cycles followed by AC (60/600 mg/m(2)) on day 1 of a 21-day cycle for three cycles (n = 17) or vice-versa (n = 16), without prophylactic granulocyte colony-stimulating factor support. In addition, we compared pre-treatment serum sErbB1 and sErbB2 protein concentrations with that of an age- and menopausal status-matched group of healthy women, and examined changes in serum sErbB1 and sErbB2 protein concentrations in these two treatment schedules. Data from each one of the two arms of the trial (docetaxel then AC, or AC and then docetaxel) were analyzed separately. Enrollment was suspended after the first-stage of accrual, based on statistical design. Confirmed objective response rates after six cycles of treatment were 35% [95% confidence interval (CI) 14% to 62%] with docetaxel then AC and 38% (95% CI 15% to 65%) with AC then docetaxel. Dose reductions were frequent and mostly due to grade 4 neutropenia. Median survival time was 2.5 years in the docetaxel then AC group, and 1.1 years in the AC then docetaxel group. Serum sErbB1 concentrations were not significantly different between the study patients and healthy women, and did not change significantly after three and six cycles of treatment. In contrast, serum sErbB2 concentrations were significantly higher in the study patients compared with healthy women and tended to decrease after three and six cycles of treatment. Response rates at the end of six cycles of treatment, which led to termination of accrual after the first stage using either the sequence of docetaxel first or docetaxel after AC chemotherapy, were lower than anticipated. However, median survival times and median progression-free survival times are similar to those reported in other studies. These data further suggest that additional studies to assess whether serum sErbB2 concentrations are useful predictors of responsiveness to chemotherapy are warranted.


Apoptotic and necrotic death mechanisms are concomitantly activated in the same cell after cerebral ischemia.
Both necrotic and apoptotic cell death mechanisms are activated after cerebral ischemia. However, whether they are concomitantly active in the same cell or in discrete cell populations is not known. We investigated activation of both pathways at the cellular level in mice brains subjected to transient or permanent focal ischemia. Four hours after ischemia, diffuse cathepsin-B spillage into cytoplasm, suggesting lysosomal leakage, was observed within neurons immunoreactive for the active form of caspase-3 (p20). Ischemic neurons with a leaky plasma membrane (positive for propidium iodide) were colabeled with caspase-cleaved actin fragment and exhibited TUNEL-positive nuclei having apoptotic morphology. At 72 hours, up to 27% of cells with caspase activity displayed morphological features suggestive of secondary necrosis. These data, demonstrating an early and concurrent increase in caspase-3 and cathepsin-B activities followed by appearance of caspase-cleavage products, DNA fragmentation, and membrane disintegration, suggest that subroutines of necrotic and apoptotic cell death are concomitantly activated in ischemic neurons and that the dominant cell death phenotype is determined by the relative speed of each process.


Combined Bone Ingrowth and Remodeling Around Uncemented Acetabular Component: A Multiscale Mechanobiology-Based Finite Element Analysis.
Bone ingrowth and remodeling are two different evolutionary processes which might occur simultaneously. Both these processes are influenced by local mechanical stimulus. However, a combined study on bone ingrowth and remodeling has rarely been performed. This study is aimed at understanding the relationship between bone ingrowth and adaptation and their combined influence on fixation of the acetabular component. Based on three-dimensional (3D) macroscale finite element (FE) model of implanted pelvis and microscale FE model of implant-bone interface, a multiscale framework has been developed. The numerical prediction of peri-acetabular bone adaptation was based on a strain-energy density-based formulation. Bone ingrowth in the microscale models was simulated using the mechanoregulatory algorithm. An increase in bone strains near the acetabular rim was observed in the implanted pelvis model, whereas the central part of the acetabulum was observed to be stress shielded. Consequently, progressive bone apposition near the acetabular rim and resorption near the central region were observed. Bone remodeling caused a gradual increase in the implant-bone relative displacements. Evolutionary bone ingrowth was observed around the entire acetabular component. Poor bone ingrowth of 3-5% was predicted around the centro-inferio and inferio-posterio-superio-peripheral regions owing to higher implant-bone relative displacements, whereas the anterio-inferior and centro-superior regions exhibited improved bone ingrowth of 35-55% due to moderate implant-bone relative displacement. For an uncemented acetabular CoCrMo component, bone ingrowth had hardly any effect on bone remodeling; however, bone remodeling had considerable influence on bone ingrowth.


Multiobjective Optimization of Silver-Nanowire Deposition for Flexible Transparent Conducting Electrodes.
Optimizing the spin coating of silver nanowires to form transparent conducting electrodes (TCE) is guided by machine learning (ML). A good TCE has two competing characteristics: high transmittance and high conductance. Optimization using a scalar figure of merit, as often done in the field, cannot satisfy the independent requirements for transmittance and conductance imposed by specific applications. By performing a Pareto front analysis based on ML models, we show that the desired outcomes of transmittance ≥ 75% and sheet resistance ≤ 15 Ω/sq are challenging but can be achieved using processing parameters identified by ML analysis.


Altered immune response to insulin in newly diagnosed compared to insulin-treated diabetic patients and healthy control subjects.
Insulin-dependent diabetes mellitus (IDDM) is the result of a T-cell mediated autoimmune beta-cell destruction, which is accompanied by autoantibodies. We analysed the cellular and humoral immune response to insulin and insulin peptides in patients with recent-onset IDDM, IDDM patients treated with insulin, non-diabetic first degree relatives and unrelated control subjects. There were no differences in T-cell reactivity to whole insulin or insulin peptides in general between age-matched groups of IDDM patients, relatives or healthy control subjects. In contrast to investigations in NOD mice, no immunodominant or disease-specific insulin peptide could be identified. Surprisingly, a positive correlation of T-cell responses to insulin with age was noticed (p < 0.005). This resulted in an inverse relation of insulin autoantibodies (IAA) and insulin reactive T-cells (p < 0.001) together with the well-described negative correlation of IAA with age. Interestingly, insulin-treated patients differed from age-matched recent-onset IDDM patients: first, simultaneous immune recognition of insulin with T-cells and IAA was only seen in patients treated for 6 months with insulin; second, insulin-treated patients rarely responded to whole insulin; third, they displayed less determinant spreading, and finally, recognition of multiple insulin peptides was not accompanied by crossreactivity to whole insulin. These distinct observations in insulin-treated IDDM patients, together with the inverse correlation between humoral and cellular responses to insulin, may result from activation or modulation of different T-cell subsets, and may be of relevance to insulin therapy trials, in which selective activation of non-destructive T-cell subsets may be a key to successful intervention.


Aerobic and anaerobic microbiology of retroperitoneal abscesses.
The aerobic and anaerobic microbiology of various types of retroperitoneal abscesses was studied by review of the clinical and laboratory data for 161 patients treated between 1974 and 1990 for such abscesses. These included 109 anterior, 8 posterior, 21 retrofascial, and 23 pelvic retroperitoneal abscesses. A total of 472 organisms (2.9 isolates/specimen)--204 aerobic and facultative (1.3/specimen), and 268 anaerobic (1.7/specimen)--were recovered. Aerobes only were recovered from 34 abscesses (21%), anaerobes only from 34 (21%), and mixed aerobic and anaerobic bacteria from 93 (58%). Polymicrobial infection was present in 132 patients (82%). The predominant aerobic and facultative isolates were Escherichia coli (60 isolates), Klebsiella pneumoniae (20), Streptococcus group D (19), and Staphylococcus aureus (11). The predominant anaerobes were Peptostreptococcus species (95 isolates), Bacteroides fragilis group (66), Prevotella species (22), and Clostridium species (22). The number of anaerobes per site always was greater than the number of aerobic or facultative organisms and was especially high in pelvic abscesses. The number of aerobic and facultative organisms was especially high in pancreatic abscesses. These data highlight the polymicrobial aerobic-anaerobic nature of retroperitoneal abscesses.


Review article: the pharmacological implications of leucocyte-endothelial cell interactions in Crohn's disease.
The importance of leucocyte-endothelial cell interactions in the inflammatory process is now recognized. In Crohn's disease, we have proposed that these interactions mediate not only the development of the parenchymal cell infiltrate, but also initiate a process (multifocal gastrointestinal infarction) that leads to ischaemic damage to the bowel wall. We review data on the actions of drugs in the treatment of Crohn's disease and, where known, we highlight their effects on leucocyte adhesion to the endothelium. Corticosteroids inhibit adhesion by inhibiting production of interleukin-1, tumour necrosis factor, interferon gamma, leukotrienes and platelet activating factor. Drugs liberating 5-aminosalicylate inhibit leukotriene production. Cyclosporin inhibits T-cell activation, and amplification of the immune response. Inhibition of leucocyte--endothelial cell interactions probably accounts for some of the beneficial effects of these drugs in Crohn's disease.


A novel device for endoscopic submucosal dissection, the Fork knife.
To introduce and evaluate the efficacy and technical aspects of endoscopic submucosal dissection (ESD) using a novel device, the Fork knife. From March 2004 to April 2008, ESD was performed on 265 gastric lesions using a Fork knife (Endo FS) (group A) and on 72 gastric lesions using a Flexknife (group B) at a single tertiary referral center. We retrospectively compared the endoscopic characteristics of the tumors, pathological findings, and sizes of the resected specimens. We also compared the en bloc resection rate, complete resection rate, complications, and procedure time between the two groups. The mean size of the resected specimens was 4.27 +/- 1.26 cm in group A and 4.29 +/- 1.48 cm in group B. The en bloc resection rate was 95.8% (254/265 lesions) in group A and 93.1% (67/72) in group B. Complete ESD without tumor cell invasion of the resected margin was obtained in 81.1% (215/265) of group A and in 73.6% (53/72) of group B. The perforation rate was 0.8% (2/265) in group A and 1.4% (1/72) in group B. The mean procedure time was 59.63 +/- 56.12 min in group A and 76.65 +/- 70.75 min in group B (P < 0.05). The Fork knife (Endo FS) is useful for clinical practice and has the advantage of reducing the procedure time.


Plasmid transfer in Streptomyces lividans: identification of a kil-kor system associated with the transfer region of pIJ101.
The 8.9-kilobase Streptomyces plasmid pIJ101 is self-transmissible at high frequency into recipient strains. By genetic analysis of the transfer region of the plasmid, we identified six plasmid-encoded loci involved in gene transfer and the associated pocking phenomenon. Two loci, kilA and kilB, could not be cloned into Streptomyces lividans on a minimal pIJ101-based replicon unless suitable kil-override (kor) genes were present, either in cis or in trans. korA could control the lethal effects of both kilA and kilB, whereas korB could control only the effects of kilB. KilB mutants were defective in their pocking reaction; kilA mutants produced no visible pocks whatsoever. Mutations in two other loci, tra and spd, produced no pocks and defective pocks, respectively. These results suggest that kilA, kilB, tra, and spd are intimately involved in plasmid transfer and that the actions of kilA and kilB are regulated by the products of the korA and korB genes.


Molecular dynamics simulations of thermal resistance at the liquid-solid interface.
Heat conduction between parallel plates separated by a thin layer of liquid Argon is investigated using three-dimensional molecular dynamics (MD) simulations employing 6-12 Lennard-Jones potential interactions. Channel walls are maintained at specific temperatures using a recently developed interactive thermal wall model. Heat flux and temperature distribution in nanochannels are calculated for channel heights varying from 12.96 to 3.24 nm. Fourier law of heat conduction is verified for the smallest channel, while the thermal conductivity obtained from Fourier law is verified using the predictions of Green-Kubo theory. Temperature jumps at the liquid/solid interface, corresponding to the well known Kapitza resistance, are observed. Using systematic studies thermal resistance length at the interface is characterized as a function of the surface wettability, thermal oscillation frequency, wall temperature, thermal gradient, and channel height. An empirical model for the thermal resistance length, which could be used as the jump coefficient of a Navier boundary condition, is developed. Temperature distribution in nanochannels is predicted using analytical solution of continuum heat conduction equation subjected to the new temperature jump condition. Analytical predictions are verified using MD simulations.


Elevated 99mTc 3PRGD2 activity in benign metastasizing leiomyoma.
PET/CT scan was performed in a 43-year-old woman to evaluate pulmonary nodules/masses. The images showed that there was only minimal FDG activity in the masses. However, these soft tissue masses in the lungs had significantly elevated (99m)Tc 3PRGD(2) activity. Pathological examination demonstrated that this patient suffered benign metastasizing leiomyoma.


In Situ Absorption and Fluorescence Microspectroscopy Investigation of the Molecular Incorporation Process into Single Nanoporous Protein Crystals.
Protein crystals exhibit distinct three-dimensional structures, which contain well-ordered nanoporous solvent channels, providing a chemically heterogeneous environment. In this paper, the incorporation of various molecules into the solvent channels of native hen egg-white lysozyme crystals was demonstrated using fluorescent dyes, including acridine yellow G, rhodamine 6G, and eosin Y. The process was evaluated on the basis of absorption and fluorescence microspectroscopy at a single-crystal level. The molecular loading process was clearly visualized as a function of time, and it was determined that the protein crystals could act as nanoporous materials. It was found that the incorporation process is strongly dependent on the molecular charge, leading to heterogeneous molecular aggregation, which suggests host-guest interaction of protein crystals from the viewpoint of nanoporous materials.


Analysis of two different tandem repetitive elements within the human apolipoprotein B gene.
A large number of copies of the sequence (dTG-dAC)n, where n is between 10 and 60, exist in the human genome, and many are useful as polymorphic markers. One of these sequences occurs about 3 kilobases 5' of the human apolipoprotein (apo) B gene as seven distinguishable alleles containing from (TG)12 to (TG)18. This repeat is also present in the DNA of other primates. A second alternating purine-pyrimidine sequence with nine dinucleotide repeats and located in intron 4 is not polymorphic. Together with the apoB hypervariable repeat immediately 3' of the gene, the (TG)n sequence will provide a useful haplotype marker capable of distinguishing a large number of human apoB alleles, some of which may be associated with disease states.


Histopathologic findings in Unna's nevus suggest it is a tardive congenital nevus.
According to A. Bernard Ackerman's clinical histopathologic classification of nevi, the essential histopathologic finding of an Unna's nevus is localization of melanocytic nevus cells to a markedly thickened papillary dermis of an exophytic lesion. In this study, we examined 94 completely resected Unna's nevi in which several sections of the same lesion could be examined. We examined that melanocytic nevus cells were not just localized to the exophytic portion but were also commonly distributed below it (81 lesions, 86.2%). Melanocytic nevus cells were found in a periadnexal distribution in most of the lesions in which they extended below the exophytic part and were most frequently noted around hair follicles (60 lesions, 63.8%), then around eccrine ducts (43 lesions, 45.7%), and least frequently around sebaceous glands or ducts (36 lesions, 38.3%). Nests of melanocytic nevus cells were present in follicular epithelium in 7 lesions, sebaceous ducts in 1 lesion, and eccrine ducts in 1 lesion. Moreover, type A nevus cells containing melanin granules were observed in 16 lesions (17.0%) when they were distributed around hair follicles, in 8 lesions (8.5%) when distributed around sebaceous glands or ducts, and in 1 lesion (1.1%) when distributed around eccrine ducts. Although Unna's nevus is clinically an acquired nevus, it has many histopathologic characteristics of a congenital melanocytic nevus and is therefore likely a tardive congenital lesion.


Acute disseminated intravascular coagulation developed after dilation and curettage in an adenomyosis patient: a case report.
We reported a rare case of acute disseminated intravascular coagulation (DIC) after dilation and curettage in an adenomyosis and missed abortion patient. The clinical performance improved after treatment with tranexamic acid, blood transfusions and subtotal hysterectomy. Hemorrhage, degeneration and necrosis were found in the myometrium. Pregnancy-related thrombotic tendency, accelerated uterus tissue injury after curettage, activation of coagulation system, microthrombosis formation, myometrium necrosis, exhaustion of coagulation factors and hyperfibrinolysis might play the crucial roles in the pathophysiology of acute DIC. Physicians should be alert that adenomyosis patients undergoing dilation and curettage may be in danger of DIC.


Research Review: The most effective parenting program content for disruptive child behavior - a network meta-analysis.
Programs to support parents are the recommended strategy to reduce disruptive child behavior problems. Efforts have been made to demonstrate which program components (i.e., clusters of techniques taught) increase program effects, but these methods fail to account for the fact that components rarely operate in isolation. We examine how combinations of components cluster together to form program types and use network meta-analysis to estimate the relative effects of these program types. We updated an existing systematic review of parenting programs for disruptive child behavior and identified 197 randomized trials. We modeled clusters of components in each trial arm and chose the best-fitting model. We subsequently took 20 draws from the probability distribution of the latent class for each arm, entered each draw into a network meta-analysis model and combined findings using Rubin's rules. Combined estimates were bootstrapped to rank the clusters. We estimated main models and separate models for prevention and treatment settings. A five-class solution fit the data best: (1) behavior management; (2) behavior management with parental self-management; (3) behavior management with psychoeducation and relationship enhancement; (4) maximal component loading and (5) no/minimal component loading (i.e. control). In the main model and in treatment settings, all four program types were effective compared to no/minimal components. In prevention settings, only behavior management and behavior management with parental self-management were effective compared to no/minimal components. Probabilistic ranking showed that overall and in treatment settings, behavior management had the largest chance, and in prevention settings, behavior management with self-management had the largest chance, of being most effective compared to no/minimal components. Programs with more focused content seem more likely to yield stronger effects, and different foci may be needed in treatment versus prevention settings. Next steps include identifying individual family differences in optimal program content.


Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function.
The recent discovery that hydrogen sulfide (H(2)S) is an endogenously produced gaseous second messenger capable of modulating many physiological processes, much like nitric oxide, prompted us to investigate the potential of H(2)S as a cardioprotective agent. In the current study, we demonstrate that the delivery of H(2)S at the time of reperfusion limits infarct size and preserves left ventricular (LV) function in an in vivo model of myocardial ischemia-reperfusion (MI-R). This observed cytoprotection is associated with an inhibition of myocardial inflammation and a preservation of both mitochondrial structure and function after I-R injury. Additionally, we show that modulation of endogenously produced H(2)S by cardiac-specific overexpression of cystathionine gamma-lyase (alpha-MHC-CGL-Tg mouse) significantly limits the extent of injury. These findings demonstrate that H(2)S may be of value in cytoprotection during the evolution of myocardial infarction and that either administration of H(2)S or the modulation of endogenous production may be of clinical benefit in ischemic disorders.


Extracellular Ca2+ sensing is modulated by pH in human osteoclast-like cells in vitro.
Osteoclasts are polarized cells with a basolateral and an apical membrane exposed to different extracellular Ca2+ ([Ca2+]o) and H+ (pHe) concentrations. Osteoclast bone resorption is inhibited in vitro by increases of [Ca2+]o slightly above physiological levels, detected by a [Ca2+]o sensing causing elevations of the intracellular signal, [Ca2+]i. Nevertheless, during bone resorption the apical membrane is exposed to [Ca2+]o severalfold higher than physiological without apparent inhibition of osteoclast functions. Because pHe facing the apical membrane is acidic, in this single-cell [Ca2+]i and intracellular pH study we addressed the question of whether the responses of human osteoclast-like cells from a giant cell tumor of bone to elevated [Ca2+]o are altered by reducing pHe. We first observed that low pHe stimulated Ca2+ efflux and cell acidification. We then demonstrated that the amplitude of the [Ca2+]o-dependent [Ca2+]i "spikes" is downregulated by low pHe, with approximately 70-fold higher [Ca2+]o required to induce significant responses at pHe 6.0 compared with pHe 7.4. Similar downregulation was observed in authentic freshly isolated rat osteoclasts. Finally, we observed that occupancy of the [Ca2+]o sensing by Ca2+ prompted rapid and transient cell acidification partially counteracted by a Na(+)-dependent amiloride derivative-sensitive H+ transport. These results demonstrate that the cascade of events triggered by activation of the [Ca2+]o sensing is affected by environmental pH and in turn influences cellular H+ transport. Such pH-related features of the [Ca2+] o sensing mechanism might be relevant for the regulation of osteoclast-like function.


Survival, by Birth Weight and Gestational Age, in Individuals With Congenital Heart Disease: A Population-Based Study.
Congenital heart disease (CHD) survival estimates are important to understand prognosis and evaluate health and social care needs. Few studies have reported CHD survival estimates according to maternal and fetal characteristics. This study aimed to identify predictors of CHD survival and report conditional survival estimates. Cases of CHD (n=5070) born during 1985-2003 and notified to the Northern Congenital Abnormality Survey (NorCAS) were matched to national mortality information in 2008. Royston-Parmar regression was performed to identify predictors of survival. Five-year survival estimates conditional on gestational age at delivery, birth weight, and year of birth were produced for isolated CHD (ie, CHD without extracardiac anomalies). Year of birth, gestational age, birth weight, and extracardiac anomalies were independently associated with mortality (all P≤0.001). Five-year survival for children born at term (37-41 weeks) in 2003 with average birth weight (within 1 SD of the mean) was 96.3% (95% CI, 95.6-97.0). Survival was most optimistic for high-birth-weight children (>1 SD from the mean) born post-term (≥42 weeks; 97.9%; 95% CI, 96.8-99.1%) and least optimistic for very preterm (<32 weeks) low-birth-weight (<1 SD from mean) children (78.8%; 95% CI, 72.8-99.1). Five-year CHD survival is highly influenced by gestational age and birth weight. For prenatal counseling, conditional survival estimates provide best- and worst-case scenarios, depending on final gestational age and birth weight. For postnatal diagnoses, they can provide parents with more-accurate predictions based on their baby's birth weight and gestational age.


Novel Echocardiography Methods in the Functional Assessment of the Newborn Heart.
Echocardiography in the neonatal intensive care unit has led to improvements in our ability to assess the neonatal heart in health and disease. Advances in neonatal cardiac imaging have provided the capability to obtain quantitative information that often supersedes the qualitative information provided by conventional methods. Novel quantitative measures of function include the assessment of the velocity of muscle tissue movement during systole and diastole using tissue Doppler velocity imaging, and evaluation of deformation and rotational characteristics of the myocardium utilizing speckle tracking echocardiography or tissue Doppler-derived strain imaging. A comprehensive understanding of these novel functional modalities, their predictive value, and limitations can greatly assist in managing both the normal and maladaptive responses in the newborn period. This article discusses the novel and emerging methods for assessment of left and right heart function in the neonatal population.


Shades of Rage: Applying the Process Model of Emotion Regulation to Managing Anger After Brain Injury.
Uncontrollable anger is common following an acquired brain injury (ABI), with impaired emotion regulation (ER) being one of the main contributors. Existing psychological interventions appear moderately effective, though studies typically include limitations such as small sample sizes, issues of long-term efficacy, and standardization of content. While ER has been a popular research field, the study of ER for anger management after ABI is less well investigated, and contains few interventions based on the widely used Process Model of ER. This review surveys the efficacy of ER strategies in individuals with ABI, and proposes a novel research design for future interventions. Recommendations are made about: strategy number and type, shared decision-making, approaches to data analysis, and mode of delivery.


The neuropsychiatry of post-traumatic stress disorder.
The publication of DSM-III introduced the diagnosis Post-Traumatic Stress Disorder (PTSD), thus providing, for the first time, a framework for studying the consequences of extremely stressful events. Previously, traumatic neuroses had attracted a wide variety of labels - as wide as the experiences that produced them. Competing explanations in psychological and biological terms have characterised the approach to these disorders, and social and legal issues have added to the confusion. In recent years, psychosocial issues have tended to dominate the literature in relation to PTSD. While acknowledging the importance of such phenomenological and psychosocial approaches, this paper seeks to redress the balance by focusing on a biological perspective.


Somatic growth in the first six months of life of infants exposed to maternal smoking in pregnancy.
Some studies suggest a relationship between maternal smoking during pregnancy and not only intrauterine fetal growth restriction or low birth weight, but also with changes in the postnatal growth and development. The objective of the present study was to investigate the effects of smoking during pregnancy on infants growth in the first 6 months of life compared with a control group and a group with idiopathic intrauterine growth restriction. Longitudinal observational study using a convenience sample of newborns divided into three groups: infants of smoking mothers (tobacco), with idiopathic intrauterine growth restriction (IUGR) and a control group. The sample was selected from two hospitals in Porto Alegre, located in southern Brazil, between 2011 and 2015. Newborns were evaluated at birth, 7 and 15 days, and in the first, third, and sixth month. Anthropometric measures were weight, length and head circumference. The growth indicators used were expressed as z-scores. The analyses were performed using the generalized estimating equation method. The sample included 273 mother/newborn pairs: 86 tobacco group, 34 IUGR group, and 153 control group. In terms of weight at birth, all groups differed significantly (p < 0.001). The birth length of tobacco and control groups were similar, but the IUGR group was lower than both (p < 0.001). We found no differences in growth trajectory between tobacco and control group, but there were differences in the growth of the IUGR group when compared with the other groups. At 6 months of age, all groups had similar anthropometric measurements. Intrauterine growth restriction had major impact on the growth trajectory of the infants studied, regardless of other factors, such as smoking and diet.


Antibody recognition of cathepsin L1-derived peptides in Fasciola hepatica-infected and/or vaccinated cattle and identification of protective linear B-cell epitopes.
Fasciola hepatica infection causes important economic losses in livestock and food industries around the world. In the Republic of Ireland F. hepatica infection has an 76% prevalence in cattle. Due to the increase of anti-helminthic resistance, a vaccine-based approach to control of Fasciolosis is urgently needed. A recombinant version of the cysteine protease cathepsin L1 (rmFhCL1) from F. hepatica has been a vaccine candidate for many years. We have found that vaccination of cattle with this immunodominant antigen has provided protection against infection in some experimental trials, but not in others. Differential epitope recognition between animals could be a source of variable levels of vaccine protection. Therefore, we have characterised for first time linear B-cell epitopes recognised within the FhCL1 protein using sera from F. hepatica-infected and/or vaccinated cattle from two independent trials. Results showed that all F. hepatica infected animals recognised the region 19-31 of FhCL1, which is situated in the N-terminal part of the pro-peptide. Vaccinated animals that showed fluke burden reduction elicited antibodies that bound to the regions 120-137, 145-155, 161-171 of FhCL1, which were not recognised by non-protected animals. This data, together with the high production of specific IgG2 in animals showing vaccine efficacy, suggest important targets for vaccine development.


[Lateral cervical branchial cysts: a retrospective study].
The cause of lateral cervical branchial cysts is debated. Some authors claim that they are congenital, whereas others believe that they are acquired, being their likely origin cystic degeneration of the cervical lymph nodes. Their protocol of study and differential diagnosis with respect to malignant neck masses are of special interest. A retrospective clinical study was made of 13 cervical branchial cysts seen by one of the authors over a decade-long period. Based on the results, their probable origin is discussed and a study protocol is proposed. Although it has been discussed by some authors, we conclude that the origin of branchial cysts cannot be determined through this type of clinical study. Computed tomography and fine-needle aspiration currently are essential diagnostic methods in the study protocol of these lesions.


Incidence of Diabetic Ketoacidosis Among Pediatrics With Type 1 Diabetes Prior to and During COVID-19 Pandemic: A Meta-Analysis of Observational Studies.
Previous reports suggest that the Coronavirus Disease-2019 (COVID-19) pandemic might have affected incidences of diabetic ketoacidosis (DKA) and new diagnoses of type 1 diabetes. This systematic review and meta-analysis aimed to estimate the risk of DKA, including severe DKA, during the COVID-19 pandemic versus the prior-to-COVID-19 period among pediatric patients with type 1 diabetes. PubMed and EMBASE were searched for observational studies investigating the risk of DKA among pediatric patients with type 1 diabetes during the COVID-19 pandemic and the prior-to-COVID-19 period. A random meta-analysis model was performed to estimate the relative risk of DKA during the COVID-19 pandemic compared to before the pandemic. Subgroup analyses were conducted based on the type 1 diabetes status, established or newly diagnosed. In addition, sensitivity analysis was conducted for studies that reported results from adjusted analysis for potential confounders using fixed effect model. A total of 20 observational studies reported the risk of DKA, of which 18 reported the risk of severe DKA. The risks of DKA and severe DKA were 35% (RR 1.35, 95%CI 1.2-1.53, I2 = 71%) and 76% (RR 1.76, 95%CI 1.33-2.33, I2 = 44%) higher in the during-COVID-19 group compared to the prior-to-COVID-19 group, respectively. Among patients with newly diagnosed type 1 diabetes, the risk of DKA was 44% higher for the during-COVID-19 group compared to the prior-to-COVID-19 group (RR 1.44, 95%CI 1.26-1.65; I2 = 64%). Only two studies reported the risk of DKA among patients with established type 1 diabetes and the cumulative risk was not statistically significant. In the sensitivity analysis, four studies reported an adjusted odds ratio (aOR) of the risk of DKA during COVID-19 compared to the prior-to-COVID-19 period. The fixed estimate from the meta-analysis found an increase in the risk of DKA in the during-COVID-19 group compared to the prior-to-COVID-19 group (aOR 2.04, 95%CI 1.66-2.50). This study showed that DKA risk, especially the risk of severe DKA, has increased significantly during the pandemic. Healthcare systems must be aware and prepared for such an increase in DKA cases and take all necessary measures to prevent future spikes during the pandemic. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=272775, identifier PROSPERO [CRD42021272775].


Intraductal ultrasonography for the examination of duodenal papillary region.
The purpose of this study was to provide basic criteria for interpreting images of the normal duodenal papillary region obtained by intraductal ultrasonography at the frequency of 20 MHz. Our in vitro examination of autopsy specimens from 15 patients revealed that the images could be classified into three patterns according to the spatial relationships between the duodenal muscularis propria and the bile duct, or the common duct. Oddi's muscle was clearly demonstrated surrounding the mucosa of the bile duct or the common duct, which was visualized as a hypoechoic layer. The images obtained using in vivo examination of 60 patients with pancreato-biliary disease via either the percutaneous or the peroral approach were similar to the images obtained in vitro. In eight patients with cancer of the papilla of Vater, the tumor was demonstrated clearly on intraductal sonograms. The intraductal imaging features of the normal papillary region were clarified, and the clinical usefulness of this technique in the evaluation of the tumor extent in patients with cancer of the papilla of Vater is suggested.


Randomized phase II study of paclitaxel/carboplatin intercalated with gefitinib compared to paclitaxel/carboplatin alone for chemotherapy-naïve non-small cell lung cancer in a clinically selected population excluding patients with non-smoking adenocarcinoma or mutated EGFR.
Considering cell cycle dependent cytotoxicity, intercalation of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) may be a treatment option in non-small cell lung cancer (NSCLC). This randomized phase 2 study compared the efficacy of paclitaxel and carboplatin (PC) intercalated with gefitinib (G) versus PC alone in a selected, chemotherapy-naïve population of advanced NSCLC patients with a history of smoking or wild-type EGFR. Eligible patients were chemotherapy-naïve advanced NSCLC patients with Eastern Cooperative Oncology Group performance status of 0-2. Non-smoking patients with adenocarcinoma or patients with activating EGFR mutation were excluded because they could benefit from gefitinib alone. Eligible patients were randomized to one of the following treatment arms: PCG, P 175 mg/m(2), and C AUC 5 administered intravenously on day 1 intercalated with G 250 mg orally on days 2 through 15 every 3 weeks for four cycles followed by G 250 mg orally until progressive disease; or PC, same dosing schedule for four cycles only. The primary endpoint was the objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity profile. A total of 90 patients participated in the study. The ORRs were 41.9 % (95 % confidence interval (CI) 27.0-57.9 %) for the PCG arm and 39.5 % (95 % CI 25.0-55.6 %) for the PC arm (P = 0.826). No differences in PFS (4.1 vs. 4.1 months, P = 0.781) or OS (9.3 vs. 10.5 months, P = 0.827) were observed between the PCG and PC arms. Safety analyses showed a similar incidence of drug-related grade 3/4 toxicity. Rash and pruritus were more frequent in the PCG than in the PC arm. PCG did not improve ORR, PFS, and OS compared to PC chemotherapy alone for NSCLC in a clinically selected population excluding non-smoking adenocarcinoma or mutated EGFR. The study is registered with ClinicalTrials.gov ( NCT01196234 ). Registration date is 08/09/2010.


Specialized structure of neural population codes in parietal cortex outputs.
Do cortical neurons that send axonal projections to the same target area form specialized population codes for transmitting information? We used calcium imaging in mouse posterior parietal cortex (PPC), retrograde labeling, and statistical multivariate models to address this question during a delayed match-to-sample task. We found that PPC broadcasts sensory, choice, and locomotion signals widely, but sensory information is enriched in the output to anterior cingulate cortex. Neurons projecting to the same area have elevated pairwise activity correlations. These correlations are structured as information-limiting and information-enhancing interaction networks that collectively enhance information levels. This network structure is unique to sub-populations projecting to the same target and strikingly absent in surrounding neural populations with unidentified projections. Furthermore, this structure is only present when mice make correct, but not incorrect, behavioral choices. Therefore, cortical neurons comprising an output pathway form uniquely structured population codes that enhance information transmission to guide accurate behavior.


In Utero Exposure to Exosomal and B-Cell Alloantigens Lessens Alloreactivity of Recipients' Lymphocytes Rather than Confers Allograft Tolerance.
According to actively acquired tolerance, antigen exposure before full immune development in fetal or early neonatal life will cause tolerance to this specific antigen. In this study, we aimed to examine whether allogeneic tolerance could be elicited by in utero exposure to surface MHC antigens of allogenic cells or soluble form of MHC exosomes. Gestational day 14 FVB/N fetuses were subjected to intraperitoneal injection of allogeneic major histocompatibility complex (MHC) exosomes or highly enriched B-cells. Postnatally, the recipients were examined for the immune responses to donor alloantigens by lymphocyte proliferative reactions and skin transplantation. In utero exposure to allogeneic MHC exosomes abolished the alloreactivity of recipients' lymphocytes to the alloantigens, but could not confer skin allograft tolerance. In utero transplantation of highly enriched allogeneic B-cells generated low-level B-cell chimerism in the recipients. However, it only extended the survivals of skin allograft by a few days despite the lack of donor-specific alloreactivity of recipients' lymphocyte. Thus, an early in utero contact with exosomal or B-cell alloantigens did not lead to full skin tolerance but rather, at best, only to delayed skin rejection in the presence of microchimerism made by B-cell inocula. These results argued against the theory of actively acquired tolerance, and implicated that in utero exposure to marrow cells in previous studies was a unique model of allo-tolerance induction that involved the establishment of significant hematopoietic chimerism. Taken together with the discovery of in utero sensitization to ovalbumin in our previous studies, the immunological consequences of fetal exposure to foreign antigens might vary according to the type or nature of antigens introduced.


[The effect of rotating magnetic fields on the growth of Deal's guinea pig sarcoma transplanted subcutaneously in guinea pigs].
The effect of rotating magnetic field (RMF) was studied on the growth of Deals' guinea pig sarcoma (DGPS) transplanted subcutaneously into the inguen of guinea pigs. The 0.2 ml of transplanted suspension contained 1.5-2.0 x 10(6) of vital DGPS cells. Over a period of 24 days the animals were daily two times exposed to RMF for 3 hours. The animals were sacrificed in chloroform anesthesia, the inguinal tumors, lungs and hearts were removed and weighed. The following findings were recorded: 1. RMF inhibited the growth of DGPS cells in experimental guinea pigs compared to control animals (p < 0.001); 2. In the experimental animals DGPS cells did not metastasize into the lung parenchyma; 3. The pathological characteristics of the tumors in the experimental and control group of guinea pigs tended to be different. (Tab. 3, Ref. 14.)


Clinical and epidemiological characteristics of 1420 European patients with mild-to-moderate coronavirus disease 2019.
The clinical presentation of European patients with mild-to-moderate COVID-19 infection is still unknown. To study the clinical presentation of COVID-19 in Europe. Patients with positive diagnosis of COVID-19 were recruited from 18 European hospitals. Epidemiological and clinical data were obtained through a standardized questionnaire. Bayesian analysis was used for analysing the relationship between outcomes. A total of 1,420 patients completed the study (962 females, 30.7% of healthcare workers). The mean age of patients was 39.17 ± 12.09 years. The most common symptoms were headache (70.3%), loss of smell (70.2%), nasal obstruction (67.8%), cough (63.2%), asthenia (63.3%), myalgia (62.5%), rhinorrhea (60.1%), gustatory dysfunction (54.2%) and sore throat (52.9%). Fever was reported by 45.4%. The mean duration of COVID-19 symptoms of mild-to-moderate cured patients was 11.5 ± 5.7 days. The prevalence of symptoms significantly varied according to age and sex. Young patients more frequently had ear, nose and throat complaints, whereas elderly individuals often presented fever, fatigue and loss of appetite. Loss of smell, headache, nasal obstruction and fatigue were more prevalent in female patients. The loss of smell was a key symptom of mild-to-moderate COVID-19 patients and was not associated with nasal obstruction and rhinorrhea. Loss of smell persisted at least 7 days after the disease in 37.5% of cured patients. The clinical presentation of mild-to-moderate COVID-19 substantially varies according to the age and the sex characteristics of patients. Olfactory dysfunction seems to be an important underestimated symptom of mild-to-moderate COVID-19 that needs to be recognized as such by the WHO.


Resisting the onset of herbivore attack: plants perceive and respond to insect eggs.
Plants can respond to attack by herbivorous insects very soon after herbivores start producing a new generation by depositing eggs onto their leaves. Egg-induced plant responses may result in killing the attacker in its egg stage. However, if the eggs do survive, they can also prime feeding-induced plant defenses against the larvae hatching from eggs. In this paper we focus first on egg-induced plant responses that resemble hypersensitive responses (HR) to phytopathogens and lead to egg desiccation or detachment from plants. We then summarize the current knowledge about egg-mediated effects on feeding-induced plant defenses against larvae. Finally, we discuss the insect species specificity of plant responses to eggs and the variability of insect susceptibility to these responses.


SENESCENCE IN NATURAL POPULATIONS OF MAMMALS: A COMPARATIVE STUDY.
Here, I use published mortality data from 56 natural populations of mammals to examine evidence for senescence, an increase in the probability of mortality with age. Data on extent of senescence and life history characteristics are compared across taxa in an attempt to test theories for the evolution of senescence in natural populations. In accord with theoretical expectation, senescence is highest in short-lived species with short generation times. In contrast to theoretical expectation, however, senescent increases in mortality rate do not begin until well after age at maturity in most cases. I also present evidence in support of the hypothesis that senescence will be lower in large-brained taxa.


EXPERIMENTAL MOLECULAR EVOLUTION OF BACTERIOPHAGE T7.
We present an analysis of molecular evolution in a laboratory-generated phylogeny of the bacteriophage T7, a virus of 40 kilo-base pairs of double-stranded DNA. The known biology of T7 is used in concert with observed changes in restriction sites and in DNA sequences to produce a model of restriction-site convergence and divergence in the experimental lineages. During laboratory propagation in the presence of a mutagen, the phage lineages changed an estimated 0.5%-1.5% in base pairs; most change appears to have been G → A or C → T, presumably because of the mutagen employed. Some classes of restriction-site losses can be explained adequately as simple outcomes of random processes, given the mutation rate and the bias in mutation spectrum. However, some other classes of sites appear to have undergone accelerated rates of loss, as though the losses were selectively favored. Overall, the wealth of knowledge available for T7 biology contributes only modestly to these explanations of restriction-site evolution, but rates of restriction-site gains remain poorly explained, perhaps requiring an even deeper understanding of T7 genetics than was employed here. Having measured these properties of molecular evolution, we programmed computer simulations with the parameter estimates and pseudo-replicated the empirical study, thereby providing a data base for statistical evaluation of phylogeny reconstruction methods. By these criteria, replicates of the experimental phylogeny would be correctly reconstructed over 97% of the time for the three methods tested, but the methods differed significantly both in their ability to recover the correct topology and in their ability to predict branch lengths. More generally, the study illustrates how analyses of experimental evolution in bacteriophage can be exploited to reveal relationships between the basics of molecular evolution and abstract models of evolutionary processes.


Optimized substrate concentrations for production of long-chain isomaltooligosaccharides using dextransucrase of Leuconostoc mesenteroides B-512F.
Isomaltooligosaccharide (IMO) is a promising dietary component with prebiotic effect, and the long-chain IMOs are preferred to short chain ones owing to the longer persistence in the colon. To establish the optimal process for synthesis of long-chain IMOs, we systematically examined the reaction condition of dextransucrase of Leuconostoc mesenteroides B-512F by changing the ratio of sucrose to maltose (varying as 1:4, 1:2, 1:1, and 2:1) and amount of each sugar (from 2% to 20%). As a result, a ratio of 2:1 (sucrose to maltose, 10:5% or 20:10%, w/v) was determined as an optimal condition for long-chain IMO synthesis (DP3-DP9) with relatively higher yields (70-90%, respectively).


Population-based study of BRCA1/2 mutations: family history based criteria identify minority of mutation carriers.
The two major susceptibility genes, BRCA1 and BRCA2, are involved in hereditary breast and ovarian cancer syndrome. Early detection of mutation carriers has crucial clinical importance, as it allows identification of women who may benefit from intensive clinical follow-up or prophylactic surgery. Generally accepted inclusion criteria for BRCA1/2 mutation testing are based either upon family history of breast or ovarian cancer or young age at cancer diagnosis. In order to analyze the impact of BRCA1/2 mutations on breast cancer development in the Czech population and to confront the clinical and histopathological data of mutation carriers with current criteria for mutation testing we examined the frequency of mutations in unselected breast cancer cases. Mutational analysis of BRCA1/2 genes performed in 679 unselected female breast cancer patients included all recurrent deleterious alterations previously identified in the Prague area and truncating mutations in the whole exon 11 of BRCA1. Within analyzed gene sequences more than 80% of mutations were identified previously in high-risk patients. A total of 16 breast cancer patients (2.4%) carried a mutation. BRCA1 mutations were identified in 14 (2.1%) whereas BRCA2 in 2 (0.3%) women. Family history of ovarian cancer was a strong predictor of a BRCA1/2 mutation (OR = 8.3; p = 0.01), however, family history of breast cancer was not indicative of carrier status. A significant association between medullary breast cancer and mutation status was observed. Current criteria for BRCA1/2 mutation testing would distinguish only 6 out of 16 (37.5%) carriers identified in our study. Ten breast cancer patients with confirmed BRCA1/2 germ-line mutation exhibited no clinical characteristics that would predict their carrier status. Therefore, we believe that the testing for BRCA1/2 mutations in the Czech Republic may not be restricted only to high-risk patients. Our results indicate that analysis of locally prevalent BRCA1/2 mutations in all breast cancer patients might extend substantially the percentage of identified mutation carriers.


Evaluation of the treatment effect of NSAIDs/TNF blockers according to different domains in ankylosing spondylitis: results of a meta-analysis.
To assess the treatment effect of NSAIDs and TNF blockers in AS according to different domains of interest. A systematic literature research was performed in electronic databases up to October 2009. All randomized controlled trials (RCTs) reporting the efficacy (on pain and/or physical function and/or acute-phase reactants) of NSAIDs/anti-TNF vs placebo in AS were selected. Pooled effect sizes were calculated by meta-analysis, using fixed or random-effect models. Optimal data to calculate the effect size were available in 8 out of the 240 selected RCTs evaluating anti-TNF and 5 of the 135 evaluating NSAIDs. For the domains pain, physical function and patient's global assessment, the treatment effect was large or medium for both TNF blockers and NSAIDs. For the domain acute-phase reactants, the effect of TNF blockers was medium [standardized mean difference (SMD) (95% CI) -0.56 (-0.70, -0.42)], whereas NSAIDs had no significant effect on acute-phase reactants {SMD [95% odds ratio (OR)] -0.09 (-0.34, 0.16)}. Finally for the domain mobility, the effect of both TNF blockers and NSAIDs was small and not significant. This study suggests that the treatment effect of NSAIDs and anti-TNF are both of relevant magnitude considering the main patient-reported outcomes but with a trend in favour of anti-TNF despite the fact that such drugs are given on top of NSAIDs in refractory patients. Moreover, a statistically significant difference was observed for the domain 'acute-phase reactants' confirming the specificity of such drug category.


[Skin changes during the course of selected endocrinologic diseases in children and adolescents].
The authors presented skin lesions which may be observed in selected endocrinopathies in children and adolescents. Functional disturbances of endocrine glands in which skin lesions may develop are dysfunction of the adrenals, gonads in case of children, thyroid diseases and diabetes type 1. The authors presented also a detailed description of skin symptoms observed in hyperthyrosis and hypothyrosis. They emphasised that the most common form of hyperthyrosis in children and adolescents is Graves disease. Also broadly dermatological lesions which may develop in diabetes type 1 they described.


Pulsed electric field for shalgam juice: effects on fermentation, shelf-life, and sensory quality.
Pulsed electric field (PEF) has become a reality in the food industry as a non-thermal application. PEF is used due to its benefits such as increasing the extraction of anthocyanin or other bioactive substances, shortening the fermentation time, and reducing the microbiological load by electroporation. This study aimed to determine the effect of PEF pretreatment on the fermentation, chemical, microbiological, and sensory properties of shalgam juice. For this purpose, PEF with 1 kV cm-1 of field strength was used as a pretreatment for shalgam juice and changes in control and PEF-treated samples were monitored during fermentation and 70 days of cold storage (4 °C). The pH and lactic acid content during fermentation were similar for both samples. The effect of PEF on pH (3.15-3.39), titratable acidity (4.35-5.49 g L-1 ), total phenolic content (279-766 mg mL-1 GAE) and antioxidant activity (694-2091 μmol Trolox mL-1 ) during storage was insignificant. PEF-treated samples had lower total aerobic mesophilic bacteria (~9%) and lactic acid bacteria (~3%) counts than the control samples at the end of 70 days. Sensory analyses performed at 30th and 60th days of storage with 74 panelists revealed that the color, taste, sourness, saltiness, bitterness, and general acceptability were not inversely affected by PEF. Our results could be a basis to produce shalgam juice commercially by PEF treatment. Although more studies with new experimental designs should be carried out, preliminary results indicated that the use of PEF might have a potential for fermented products such as shalgam juices. © 2023 Society of Chemical Industry.


Current practice in the management of temporomandibular disorders.
There has been much debate and conflicting opinion on the appropriate management of temporomandibular disorders (TMDs). However, the question of the relevance of occlusion in both the aetiology and management of TMD has been somewhat clarified in recent years and this article attempts to summarize current thinking on this issue and also to provide practical guidance on the construction of stabilization splints. Various other forms of treatment are discussed and evidence is presented to help in judging their relevance. Bruxism is relatively common in patients with TMD and guidance relating to the management of this problem is also presented. Temporomandibular disorders are common, so knowledge of their treatment is of relevance to the primary care practitioner.


Effects of intermittent hPTH(1-34) alone and in combination with 1,25(OH)(2)D(3) or risedronate on endosteal bone remodeling in canine cancellous and cortical bone.
Therapies utilizing intermittent human parathyroid hormone(1-34) (hPTH[1-34]) in combination with other agents have recently been proposed as possible anabolic regimens for the treatment of osteoporosis. We conducted a 24 week study in aged beagle dogs to determine the effects of intermittent hPTH(1-34) administered alone or in combination with 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on the endosteal remodeling in cancellous and cortical bone. Additionally, we tested the interaction between hPTH(1-34) and a new potent bisphosphonate, risedronate. The three treatment groups were compared with a vehicle control group. Kinetic reconstruction of the remodeling unit revealed substantial differences between the groups in resorption and formation at the basic multicellular unit level. Although the estimates of final erosion depth were unaffected by treatment, tunneling resorption was noted in six of the eight dogs administered hPTH(1-34) alone. These qualitative morphological changes in the resorption lacunae were attenuated or absent in dogs administered hPTH(1-34) in combination with either 1,25(OH)(2)D(3) or risedronate. Functional periods for resorption were significantly increased, and the resorption rates were significantly decreased in the hPTH(1-34) + risedronate group. Analyses of the formative site demonstrated that the wall thickness was significantly increased and the bone balance significantly more positive in all three hPTH(1-34) treatment groups. The most positive bone balance was achieved in the combined hPTH(1-34) + risedronate group (+ 15.6 + or - 14.2 mm, p <0.05). Increases in the mineral apposition rate in the early phases of the formative period suggest that an increase in osteoblastic activity (number or function) may contribute to the increase in wall thickness. Treatment with hPTH(1-34) alone or in combination with 1,25(OH)(2)D(3) caused an approximately 2-fold increase in the activation frequency in cancellous bone, which was essentially normalized to control values by the coadministration of risedronate. The impact of these changes on the cancellous bone microstructure was significant only in the combined hPTH(1-34) + risedronate group where normalized bone turnover in the face of a positive bone balance effected a significant increase in the trabecular thickness. Analyses of sequential fluorochrome labels, administered to reconstruct the temporal changes in intracortical activation, demonstrated the presence of an apparent cyclic pattern of activation in the cortex of placebo-treated dogs. Generally, activation was increased throughout the study in dogs administered hPTH(1-34) alone or in combination. However, in the hPTH(1-34) + risedronate group, activation was significantly blunted toward the end of the study, and the cyclic pattern of activation was modulated. These data suggest that intermittent hPTH(1-34) in combination with risedronate may be superior to hPTH(1-34) in combination with 1,25(OH)(2)D(3) as a therapeutic regimen for osteoporosis due to the protective effect of this bisphosphonate on the cortical and endocortical envelope.


Control of HIV-1 replication in elite suppressors.
HIV-1 infection usually results in high level of viral replication leading to a progressive decline of CD4+ T cells and eventually to full blown AIDS. Long term non-progressors (LTNPs) are patients who have stable CD4 counts for more than 5 years without antiretroviral therapy. Most of these patients have detectable levels of viremia and eventually will progress to AIDS. Elite controllers or suppressors (ES) represent a distinct subset of untreated patients who appear to be able to completely control viral replication. These patients maintain viral loads below the limit of detection of commercial assays for many years and generally do not show any clinical signs of disease progression. The mechanisms responsible for this remarkable control may lead to the design of effective HIV-1 vaccines.


Thromboembolism in Patients with Cancer.
One hundred and forty years ago, Armand Trousseau described phlegmasia alba dolens as a sign of internal malignancy. Nowadays, it is commonly believed that the presence malignant tumaor increases the risk of venous thromboembolism (i.e deep vein thrombosis and pulmonary embolism) However, cancer is usually associated with other factors such as old age, extensive surgery,immobility, etc., which may predispose to thromboembolism. The majority of thrombotic events occur in the venous system; the incidence of arterial thrombosis is much lower.Recurrent thromboembolism in cancer patients frequently and diminishes the quality of life of the patients.Furthermore, if the thromboembolism is massive, destipte of early and aggressive treatment, it may result in death. In this article, we review thromboembolic complications in cancer patients.


Patients' information and perspectives on biosimilars in rheumatology: A French nation-wide survey.
To assess the patients' information about biosimilars and to identify the patients' incentives and deterrents to concur with the use of biosimilars. Nation-wide cross-sectional study assessing information and concerns about biosimilars of French patients treated for rheumatic inflammatory diseases, whether they were treated or not by a biological DMARD. The assessment was available online from March to July 2017. Among the 629 respondents, 43% knew what biosimilars were. The main sources of information were rheumatologists and patient associations. Among patients treated with a biosimilar, 44% were not informed before they received the treatment. The patients' concerns focused on the non-similar molecular structure (46%), efficacy (60%) and safety (57%) comparatively to the originator biologic. 15% of respondents would refuse to switch their biologic to its biosimilar. More than 50% of respondents would warily accept to switch medications and interrupt the treatment if in doubt. Being informed about biosimilars and a good understanding of the definition of biosimilars were characteristics associated with better adherence to biosimilars. The rheumatologist was considered the most influent source of information about biosimilars and was considered reliable when deciding to switch a biologic to its biosimilar. Patient were reluctant to substitution of the medications by pharmacists (2%). Medico-economical issues acted as an incentive and a deterrent to accept the switch of medication. Biosimilars are largely unknown to patients. Information seems to be instrumental in improving the patients' adherence to biosimilars and could help preserving the therapeutic relationship and avoiding a nocebo effect.


18F-Fluorocholine PET/CT Is More Sensitive Than 11C-Methionine PET/CT for the Localization of Hyperfunctioning Parathyroid Tissue in Primary Hyperparathyroidism.
Preoperative molecular imaging is paramount to direct surgery in primary hyperparathyroidism (pHPT). We investigated the diagnostic performance of 18F-fluorocholine (18F-FCH) PET/CT compared with 11C-methionine (11C-MET) PET/CT for localization of hyperfunctioning parathyroid tissue in patients with pHPT and negative or inconclusive 99mTc-sestaMIBI (99mTc-MIBI) SPECT findings. Methods: Fifty-eight patients with biochemical evidence of pHPT and negative or inconclusive 99mTc-MIBI SPECT findings were referred for presurgical detection and localization of hyperfunctioning parathyroid tissue by 11C-MET and 18F-FCH PET/CT. The PET/CT results were classified into 3 categories (positive, inconclusive, or negative) based on the nodular aspect of tracer uptake and the visualization of corresponding nodules on CT. The PET/CT results were correlated with the surgical and histopathologic findings, which were used as the gold standard. Results: Fifty-three patients were included for analysis. 18F-FCH PET/CT was positive in 39 patients (74%), inconclusive in 5 (9%), and negative in 9 (17%), compared with 25 (47%), 12 (23%), and 16 (30%), respectively, for 11C-MET PET/CT. 18F-FCH localized 11 additional foci (6 positive and 5 inconclusive), compared with 11C-MET. Twenty-six patients (sex ratio, 10/16 M/F) underwent surgery, with resection of 31 lesions (22 adenomas, 6 hyperplastic glands, and 3 carcinomas) and 1 normal gland. At follow-up, 21 patients (81%) were considered cured after surgery, whereas 3 patients (12%) had persistence of hypercalcemia. With inconclusive cases being considered negative, 18F-FCH PET/CT correctly localized 26 lesions in 24 of 26 patients (92%), compared with 16 lesions in 15 of 26 patients (58%) localized by 11C-MET PET/CT. Per-patient-based sensitivity and positive predictive value were 96% and 96%, respectively, for 18F-FCH and 60% and 94%, respectively, for 11C-MET (P < 0.0001). Per-lesion-based sensitivity and positive predictive value were 84% and 90%, respectively, for 18F-FCH and 52% and 94%, respectively, for 11C-MET (P < 0.0001). Conclusion: In the presence of biochemical evidence of pHPT with negative or inconclusive 99mTc-MIBI SPECT findings, 18F-FCH PET/CT performs better than 11C-MET PET/CT for the detection of pathologic parathyroid tissue, allowing localization of parathyroid adenoma or hyperplasia in 96% of patients.


Prevalence and characteristics of comorbid stroke and traumatic brain injury in a real-world population: findings from a nationally representative cross-sectional survey in China.
In China, data on the prevalence and characteristics of comorbid stroke and traumatic brain injury (TBI) in real-world populations are still lacking but of paramount importance for the evidence-based prevention and control of the comorbidity of the two diseases. This study aimed to investigate the prevalence and characteristics of comorbid stroke and TBI in a real-world population. In 2013, a nationally representative, door-to-door survey on stroke and TBI using a complex, multistage, probability sampling design was conducted among approximately 600,000 participants from 155 urban and rural areas in China (Ethic ID: KY2013-006-01). The weighted prevalence of comorbid stroke and TBI was estimated using individuals' final weight. A Poisson regression analysis was used to compare the rate ratio of the comorbidity prevalence among different subgroups of the population, including age, sex, place of residence, and geographic location subgroups. For analyses of associations between the comorbidities and predictors of interest, all other variables were adjusted for in a multinomial logistic regression model. Among the 596,536 people, 219 patients with comorbid stroke and TBI were identified. The point prevalence of comorbid stroke and TBI weighted to the China 2010 census population was 29.30 (95% CI: 22.69-37.84) per 100,000 population in China. The adjusted prevalence of post-TBI stroke in patients with previous TBI was significantly higher than that of post-stroke TBI in patients with previous stroke (6021.3 vs. 811.1 per 100,000 people; rate ratio: 11.001; 95% CI: 8.069-14.998). Patients with nonconcussion had significantly higher rates of both pre-stroke TBI (odds ratio: 4.694; 95% CI: 3.296-6.687) and post-stroke TBI (odds ratio: 6.735; 95% CI: 3.719-12.194) than patients with concussion. Compared to patients with ischaemic stroke, patients with subarachnoid haemorrhage (odds ratio: 2.044; 95% CI: 1.097-3.809) and intracerebral haemorrhage (odds ratio: 1.903; 95% CI: 1.296-2.795) had significantly higher rates of post-TBI stroke. The high prevalence of stroke among TBI patients is becoming a new public health issue. TBI patients, especially those with nonconcussion TBI, are more likely to develop comorbid stroke and TBI than stroke patients, especially ischaemic stroke patients.


Giant hypertrophied anal papilla. Case report.
Anal papillae, polypoid lesions formed by hyperplasia of connective tissue in the vicinity of the anal columns, are usually small and asymptomatic. A rare case of giant hypertrophied anal papilla complicated by massive anal bleeding and prolapse is reported.


Wound keratins in the regenerating epidermis of lizard suggest that the wound reaction is similar in the tail and limb.
The keratin cytoskeleton of the wound epidermis of lizard limb (which does not regenerate) and tail (which regenerates) hase been studied by qualitative ultrastructural, immunocytochemical, and immunoblotting methods. The process of re-epithelialization is much shorter in the tail than in the limb. In the latter, a massive tissue destruction of bones, and the shrinkage of the old skin over the stump surface, delay wound closure, maintain inflammation, reduce blastemal cell population, resulting in inhibition of regeneration. The expression of special wound keratins found in the newt epidermis (W6) or mammalian epidermis (K6, K16, and K17) is present in the epidermis of both tail and limb of the lizard. These keratins are not immunolocalized in the migrating epithelium or normal (resting) epidermis but only after it has formed the thick wound epithelium, made of lacunar cells. The latter are proliferating keratinocytes produced during the cyclical renewal or regeneration of lizard epidermis. W6-immunolabeled proteic bands mainly at 45-47 kDa are detected by immunoblotting in normal, regenerating, and scarring epidermis of the tail and limb. Immunolabeled proteic bands at 52, 62-67 kDa (with K6), at 44-47, 60, 65 kDa (with K16), and at 44-47 kDa (with K17) were detected in normal and regenerating epidermis. It is suggested that: (1) these keratins constitute normal epidermis, especially where the lacunar layer is still differentiating; (2) the wound epidermis is similar in the limb and tail in terms of morphology and keratin content; (3) the W6 antigen is similar to that of the newt, and is associated with tonofilaments; (4) lizard K6 and K17 have molecular weights similar to mammalian keratins; (5) K16 shows some isoforms or degradative products with different molecular weight from those of mammals; (6) K17 increases in wound keratinocytes and localizes over sparse filaments or small bundles of short filaments, not over tonofilaments joined to desmosomes; and (7) failure of limb regeneration in lizards may not depend on the wound reaction of keratinocytes.


Radiofrequency Procedures to Relieve Chronic Knee Pain: An Evidence-Based Narrative Review.
Chronic knee pain from osteoarthritis or following arthroplasty is a common problem. A number of publications have reported analgesic success of radiofrequency (RF) procedures on nerves innervating the knee, but interpretation is hampered by lack of clarity regarding indications, clinical protocols, targets, and longevity of benefit from RF procedures. We reviewed the following medical literature databases for publications on RF procedures on the knee joint for chronic pain: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Google Scholar up to August 9, 2015. Data on scores for pain, validated scores for measuring physical disability, and adverse effects measured at any timepoint after 1 month following the interventions were collected, analyzed, and reported in this narrative review. Thirteen publications on ablative or pulsed RF treatments of innervation of the knee joint were identified. A high success rate of these procedures in relieving chronic pain of the knee joint was reported at 1 to 12 months after the procedures, but only 2 of the publications were randomized controlled trials. There was evidence for improvement in function and a lack of serious adverse events of RF treatments. Radiofrequency treatments on the knee joint (major or periarticular nerve supply or intra-articular branches) have the potential to reduce pain from osteoarthritis or persistent postarthroplasty pain. Ongoing concerns regarding the quality, procedural aspects, and monitoring of outcomes in publications on this topic remain. Randomized controlled trials of high methodological quality are required to further elaborate role of these interventions in this population.


Distraction osteogenesis enhanced by osteoblastlike cells and collagen gel.
Femoral distraction was done in rats to determine whether the injection of osteoblastlike cells with collagen gel into the distracted callus was useful for new bone formation. The cells were obtained from the femoral marrow of Sprague-Dawley rats and cultured for approximately 3 weeks. These rats were divided into four groups. The rats in Group A received injections of physiologic saline, those in Group B received injections of collagen gel, those in Group C received injections of cells, and those in Group D received injections containing a mixture of cells and collagen gel. The distracted areas were harvested and evaluated by histologic analysis, radiography, three-point bending testing, and the weight of femoral ash. Histologic evaluation did not show an immunoreaction between the donor and recipient. Radiographs showed that Group D had the most callus, and the fracture strength in this group as determined by the three-point bending test was higher than in Group A at 2, 4, and 6 weeks after elongation was completed. Group D showed a significant difference in the ash weight of the distracted femurs at 2 weeks. The current study showed that osteoblastlike cells with collagen gel promoted new bone formation in the distracted gap, and shortened the consolidation period.