Early pre-B cells from normal and X-linked agammaglobulinaemia produce C mu without an attached VH region.
Differentiation of B lymphocytes follows an ordered pathway marked by somatic rearrangements of immunoglobulin heavy- and light-chain genes in conjunction with cellular transitions. Although low level constitutive transcription of the mu heavy-chain constant region (C mu) genes may occur in early precursor cells, activation of synthesis and translation of complete mu RNA is thought to accompany somatic rearrangements of DNA. Cytoplasmic mu-chain protein serves as a marker for pre-B cells, the earliest cells committed to differentiation into B lymphocytes, mu-chain gene expression in pre-B cells pre-cedes rearrangement and expression of light-chain genes. We now report that early human pre-B cells, Epstein--Barr virus transformed pre-B cells, and pre-B cell hybrid analogues, produce C mu without the normally associated heavy-chain variable (VH) region. Approximately 5% of normal pre-B cells from adult human bone marrow produce these incomplete mu-chains. Pre-B cells from three patients with X-linked agammaglobulinaemia are exclusively of this immature form, producing C mu without associated VH. This immune deficiency disease represents a block in differentiation secondary to failure to express VH genes.


Estimation of daily exposure to 4-hydroxy-2-alkenals in Korean foods containing n-3 and n-6 polyunsaturated fatty acids.
4-Hydroxy-2-alkenals are cytotoxic aldehydes generated from the oxidation of n-3 and n-6 polyunsaturated fatty acids. The compounds have shown various biological effects via Schiff base adducts or Michael addition adducts at levels higher than physiological ones. To assess human exposure to 4-hydroxy-2-alkenals in the diet, 4-hydroxy-2-alkenals in vegetable oils, fish and shellfish were monitored using GC/MS/SIM. 2001 National Health and Nutrition Survey (2002) data were employed for the dietary intake pattern. The Korean daily exposure to 4-hydroxy-2-alkenals, excluding a possible one from fried food, was 4.3 microg day-1, constituted of 1.6 microg 4-hydroxy-2-hexenal (HHE) and 2.7 microg 4-hydroxy-2-nonenal (HNE). It was calculated that Koreans could be additionally exposed to more than 11.8 microg day-1 4-hydroxy-2-alkenal from fried foods. Thus, the combined exposure would be 16.1 microg day-1, which corresponds to 0.3 microg kg-1 body weight day-1 for a 60 kg Korean adult. In spite of the biological toxicity of 4-hydroxy-2-alkenals, the risk for human could not be quantified due to the lack of a virtually safe dose of the compounds. However, considering the basal level of 4-hydroxy-2-alkenals in many tissues, the present value from the diet may not pose a significant risk for human health.


The promise and perils of an Alzheimer disease vaccine: a video debate.
Alzheimer's disease (AD) is a critical health care problem that has considerable social and economic impact on society. Effective treatments have been elusive. One major causal factor for the disease is believed to be the deposition of amyloid fibrils in the brain, which ultimately leads to neurodegeneration and cognitive dysfunction. Based on the amyloid hypothesis of Alzheimer's disease, many therapies presently target the amyloid beta (Abeta) peptide, the monomeric protein fragment that assembles to form fibrils. This video article takes the form of a debate between Dr. Morgan and Dr. Landreth on the merits and drawbacks of an Alzheimer's disease vaccine. Click on Supplemental Material to watch the streaming video.


Requirement of caspases and p38 MAPK for TRAIL-mediated ICAM-1 expression by human astroglial cells.
Among tumor necrosis factor (TNF) superfamily, TNF-related apoptosis inducing ligand (TRAIL) along with TNF-alpha and FasL is known as death ligand due to its selective cytotoxicity against transformed tumor cells. TRAIL can also induce alternative angiogenic and/or proinflammatory signals other than apoptosis, however, the molecular mechanisms responsible for the alternative signals have not been detailed yet. Intercellular adhesion molecule-1 (ICAM-1) is thought to be involved in the processes of metastasis and angiogenesis in various tumors. We investigated the molecular mechanisms responsible for ICAM-1 expression by death ligands in human astroglial cells to delineate the alternative signals of these ligands. Here, we demonstrate that (1) death ligands induced expression of ICAM-1 at the mRNA and protein levels in human astroglial cells; (2) pre-treatment of z-VAD-fmk and/or SB202190 suppressed death ligand-induced ICAM-1 expression and subsequent adhesion of activated monocytic cells; and (3) inhibition of caspase suppressed death ligand-induced phosphorylation of p38 MAPK and IKK. These findings suggest biological function of death receptors other than apoptosis in human astroglial cells, and the involvement of caspase and/or p38 MAPK in alternative signaling through death receptors.


Emergency therapy of diabetic crises: insulin overdose, diabetic ketoacidosis, and hyperosmolar coma.
Three types of diabetic crises occur: insulin overdose, diabetic ketoacidosis, and hyperosmolar coma. Neurologic signs may accompany each of these syndromes, and each must be differentiated quickly by the emergency clinician so that an appropriate treatment plan can be initiated. The basic goal is to restore metabolic derangements and to stabilize the patient so that it can then be managed more routinely as an uncomplicated diabetic.


Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing.
Adenovirus vectors are expected to be a powerful tool for gene therapy to treat severe fractures. Adenovirus invades cells through binding to the coxsackievirus and adenovirus receptor (CAR) on the cell membrane. CAR expression is low in normal adult animals, but it is induced on regenerating cells in some experimental models. We made a rib fracture model in mice and evaluated the histological changes and CAR mRNA expression by RT-PCR 1, 5, 10, 14, and 21 days after the fracture. CAR mRNA was expressed exclusively in the fractured ribs at each time point, but not in the normal ribs. We detected the CAR protein immunohistochemically in fibroblast-like cells in the fracture callus on days 10 and 14 after fracture. In situ hybridization showed that these fibroblast-like cells expressed mRNA of type I collagen and osteopontin, but not osteocalcin, defining the cells as immature osteoblasts. We then transferred small doses (10(4)-10(8) PFU) of lacZ-expressing adenovirus vector into immature osteoblasts on day 14. beta-galactosidase was detected only on the immature osteoblasts at every dose. Immature osteoblasts play an important role in the matrix replacement step in fracture healing. CAR-mediated gene transfer into immature osteoblasts can be reasonable for adenovirus-mediated treatment of fracture healing.


Sunlight mutagenesis: changes in mutational specificity during the irradiation of phage M13mp2.
We reported previously that the mutations in phage M13mp2, a single-stranded DNA phage, induced by sunlight exposure are predominated by G-to-C transversions. We have now made an unexpected observation that an exposure to sunlight for a short period of time results in induction mainly of C-to-T transitions while a longer exposure results in the induction of G-to-C transversions. This peculiar phenomenon suggests that DNA damage formed by initial sunlight exposure can be transformed during an elongated exposure. 7, 8-Dihydro-8-oxoguanine (8-oxoG) in DNA might be involved in the shift of the mutational specificity, as 8-oxoG was formed in the phage DNA upon the sunlight exposure. We also compared the mutagenic activity of UVB irradiation with that of sunlight exposure. The results demonstrate that the genotoxic properties of sunlight and UVB in phage M13mp2 mutagenesis are different. The shift in the mutational specificity associated with the dose of the sunlight may call for general cautions in the studies of agent-induced mutagenesis.


Idiopathic central diabetes insipidus presenting in a very low birth weight infant successfully managed with lyophilized sublingual desmopressin.
Neonatal central diabetes insipidus (DI) is an extremely rare disorder that can cause severe morbidity and mortality. We have reported a very low birth weight infant with idiopathic central DI presenting in the first month of life who was successfully treated with sublingual desmopressin therapy. In this report, we emphasize that central DI should be kept in mind in an infant with unexplained hypernatremia and polyuria. Timely diagnosis and treatment with lyophilized desmopressin may prevent severe morbidity and mortality.


Treatment of recurrent and metastatic cervical cancer with cis-platin, doxorubicin, and cyclophosphamide.
The combination of cisplatin, doxorubicin, and cyclophosphamide was used to treat 28 patients with recurrent and metastatic cervical cancer. Five patients had a complete response and one patient had a partial response, yielding a total response rate of 21%. Eleven patients had stable disease. The median survival for the whole group was 42 weeks. Responders had a statistically significant prolongation of survival at a median of 113 weeks (P less than 0.01). There was no statistically significant difference in progression-free interval between responders and patients with stable disease. The overall median progression-free survival was 26 weeks. The toxicities noted were primarily nausea, vomiting, and myelosuppression. The combination of cis-platin, doxorubicin, and cyclophosphamide has modest effectiveness in the treatment of metastatic or recurrent carcinoma of the cervix.


Evaluating connections between personal well-being and adoption of landscape best management practices: An audience segmentation study.
Integrated pest management and outdoor water conservation comprise key practices encouraged by nonformal educators who work with the public to address significant issues related to water quality and availability. Disconnects among diverse audiences and educational programs pose challenges in achieving the goals of these types of programs. To discern a potential nonformal educational programming strategy, we conducted audience segmentation research incorporating residential environmental landscape best management practices and compared resulting subgroups' characteristics. We explored this paradigm through the context of Extension education and used a nationally-distributed electronic survey instrument to measure well-being and landscape management perceptions and practices in the United States. We collected 2601 complete survey responses and employed cluster analysis to divide the respondents into homogenous subgroups, followed by analysis of variance and chi-square analyses to identify differences among the subgroups. The group that indicated the highest level of engagement with water conservation and IPM practices also had significantly higher well-being, demonstrating the potential to align IPM education with more commonly promoted conservation practices. Membership in the highest IPM and water conservation group was related to several socio-demographic characteristics, including age, homeownership, and homeowners' association membership. This group was also most likely to engage with educational programs. Understanding these indicators of engagement in landscape best management practices and nonformal education, along with higher well-being, may be useful in determining target audiences and potential engagement with nonformal education programs.


Prospective clinical trial evaluating vulnerability and chemotherapy risk using geriatric assessment tools in older patients with lung cancer.
In Japan, the number of older patients with cancer has been increasing. Assessment of performance status, cognitive function and social background is necessary for the treatment of older patients. The aims of the present study were: (i) to establish an evaluation system using electronic medical records; and (ii) to distinguish older patients as fit versus vulnerable or frail according to a geriatric assessment (GA) system score. We incorporated GA tools in our electronic medical records system and carried out comprehensive assessments for patients with newly diagnosed lung cancer aged ≥65 years. The decision about primary treatment followed consultation with the clinical team and was not guided by GA scores. Subsequent treatment and outcomes were recorded. A total of 100 patients had completed GA. The average age was 75 years (range 65-94 years). Regarding GA results, 63% were positive on the Comprehensive Geriatric Assessment 7, 39% on the Vulnerable Elderly Survey-13 and 84% on the Geriatric 8. The percentage of vulnerable patients (positive on all three GA) was significantly higher in the non-standard therapy group (n = 19) than in the standard therapy group (n = 81; 78.9% vs 21.0%, P < 0.001). Among vulnerable patients who received standard therapy, 47% discontinued chemotherapy as a result of toxicity. Even if a patient was considered vulnerable based on GA scores, chemotherapy is possibly safe for those with EGFR mutations. We confirmed the feasibility of this system. During decision-making for older patients with cancer, a combination of GA helps prevent undertreatment or overtreatment. Geriatr Gerontol Int 2019; 19: 1108-1111.


Prevention of intractable partial seizures by intermittent vagal stimulation in humans: preliminary results.
Intermittent stimulation of the vagus nerve in four patients resulted in complete seizure control in two, a 40% reduction of seizure frequency in one, and no change in seizure frequency in the other. Side effects (hoarseness, stimulation sensation in the neck, and hiccups) were transient and occurred concomitantly with stimulation. All patients tolerated increasing stimulation parameters well. The results, however, are inconclusive because of the brief duration (6-12 months) of follow-up. Vagal stimulation represents a novel approach for seizure control in patients who have intractable epilepsy, but additional studies are needed to clarify the efficacy and safety of the procedure and to define selection criteria for patients.


Structure and hydrogel formation studies on homologs of a lactoglobulin-derived peptide.
In order to study the impact of the amino acid sequence on the morphology of peptide-based nanostructures and their hydrogel formation, we designed a series of analogs of a milk-derived octapeptide (OP), mainly using strategic amino acid substitutions. Electronic transmission microscopy (TEM) and circular dichroism (CD) spectropolarimetry were used to analyze the nanostructures formed, and to characterize some structural features of the modified peptides. Further, the potential to form hydrogels was investigated for all of the analogous peptides. We learned that those able to undergo secondary structure transition to β-sheet conformation form strong gels. The results reported highlight some key structural properties that explain the self-assembly propensity of Peptide OP.


Detecting genetic responses to environmental change.
Changes in environmental conditions can rapidly shift allele frequencies in populations of species with relatively short generation times. Frequency shifts might be detectable in neutral genetic markers when stressful conditions cause a population decline. However, frequency shifts that are diagnostic of specific conditions depend on isolating sets of genes that are involved in adaptive responses. Shifts at candidate loci underlying adaptive responses and DNA regions that control their expression have now been linked to evolutionary responses to pollution, global warming and other changes. Conversely, adaptive constraints, particularly in physiological traits, are recognized through DNA decay in candidate genes. These approaches help researchers and conservation managers understand the power and constraints of evolution.


Osteogenesis, angiogenesis and immune response of Mg-Al layered double hydroxide coating on pure Mg.
Layered double hydroxides (LDHs) are widely studied to enhance corrosion resistance and biocompatibility of Mg alloys, which are promising bone implants. However, the influence of LDH coating on the osteointegration of Mg implants lacks of a systematic study. In this work, Mg-Al LDH coating was prepared on pure Mg via hydrothermal treatment. The as-prepared Mg-Al LDH coated Mg exhibited better in vitro and in vivo corrosion resistance than bare Mg and Mg(OH)2 coated Mg. In vitro culture of mouse osteoblast cell line (MC3T3-E1) suggested that Mg-Al LDH coated Mg was more favorable for its osteogenic differentiation. In vitro culture of HUVECs revealed that cells cultured in the extract of Mg-Al LDH coated Mg showed superior angiogenic behaviors. More importantly, the immune response of Mg-Al LDH coated Mg was studied by in vitro culturing murine-derived macrophage cell line (RAW264.7). The results verified that Mg-Al LDH coated Mg could induce macrophage polarize to M2 phenotype (anti-inflammatory). Furthermore, the secreted factor in the macrophage-conditioned culture medium of Mg-Al LDH group was more suitable for the bone differentiation of rat bone marrow stem cells (rBMSCs) and the angiogenic behavior of human umbilical vein endothelial cells (HUVECs). Finally, the result of femoral implantation suggested that Mg-Al LDH coated Mg exhibited better osteointegration than bare Mg and Mg(OH)2 coated Mg. With favorable in vitro and in vivo performances, Mg-Al LDH is promising as protective coating on Mg for orthopedic applications.


Management of venous thromboembolism in cancer patients: Considerations about the clinical practice guideline update of the American society of clinical oncology.
The American Society of Clinical Oncology (ASCO) recently updated their clinical practice guidelines. The most novel aspect of this update is represented by the introduction of DOACs as pharmacological options both for prophylaxis and treatment of VTE in patients with cancer. The heterogeneity of the cancer population in terms of type and stage of the malignancy, presence of comorbidities, and variability in cancer treatments and prognosis represent the major challenge of managing VTE in patients with cancer. The use of VTE prophylaxis is currently recommended in cancer patients admitted to the hospital for an acute illness or reduced mobility, but no sufficient information is available on the risk of bleeding during thromboprophylaxis. Concerning the thromboprophylaxis in ambulatory cancer patients receiving chemotherapy, further refinement of existing risk models or development of new models are needed for improving risk stratification to identify high-risk cancer patients. The updated ASCO guidelines recommend the use of DOACs (edoxaban and rivaroxaban) for treatment of VTE in patients with cancer. However, Major concerns on "real-life" use of DOACs in patients with cancer are highlighted especially for the bleeding risk in patients with gastrointestinal cancers and the potential drug-drug interactions with specific anticancer therapies. CONCLUSIONS: Uncertainties to the updated ASCO guidelines remain concerning a number of indications on prophylaxis and treatment due to the limited evidence available. These limitations determine the low strength of the recommendations. The ongoing studies will contribute to refine the best management of patients with cancer-associated VTE.


[Universitarization of nursing education: promising experiments].
In the context of the universitarization of paramedical professions, the call for experimental projects provided for in the law of July 22, 2013 on higher education and research and the decree of April 26, 2022, many projects have emerged with the aim of strengthening exchanges between training courses in the health professions and encouraging the emergence of innovative courses for nursing students. Two of these projects are underway at the University of Paris-Est Créteil.


Experimental study of the pharmacokinetics of a tryptophan-containing dipeptide GB-115.
Pharmacokinetics of an original compound GB-115 (N-phenylhexanoylglycyltryptophan) synthesized on the basis of the structure of endogenous tetrapeptide cholecystokinin-4 was studied by means of high-performance liquid chromatography. Pharmacokinetic parameters were calculated after intravenous and peroral administration of GB-115. Our results indicate that this dipeptide is resistant to peptidases. The absolute bioavailability of GB-115 is 4.65%.


Regulation of chemoresistance via alternative messenger RNA splicing.
The acquisition of resistance to chemotherapy is a significant problem in the treatment of cancer, greatly increasing patient morbidity and mortality. Tumors are often sensitive to chemotherapy upon initial treatment, but repeated treatments can select for those cells that were able to survive initial therapy and have acquired cellular mechanisms to enhance their resistance to subsequent chemotherapy treatment. Many cellular mechanisms of drug resistance have been identified, most of which result from changes in gene and protein expression. While changes at the transcriptional level have been duly noted, it is primarily the post-transcriptional processing of pre-mRNA into mature mRNA that regulates the composition of the proteome and it is the proteome that actually regulates the cell's response to chemotherapeutic insult, inducing cell survival or death. During pre-mRNA processing, intronic non-protein-coding sequences are removed and protein-coding exons are spliced to form a continuous template for protein translation. Alternative splicing involves the differential inclusion or exclusion of exonic sequences into the mature transcript, generating different mRNA templates for protein production. This regulatory mechanism enables the potential to produce many different protein isoforms from the same gene. In this review I will explain the mechanism of alternative pre-mRNA splicing and look at some specific examples of how splicing factors, splicing factor kinases and alternative splicing of specific pre-mRNAs from genes have been shown to contribute to acquisition of the drug resistant phenotype.


Amperometric microbial biosensor for p-nitrophenol using Moraxella sp.-modified carbon paste electrode.
An amperometric microbial biosensor for highly specific, sensitive and rapid quantitative determination of p-nitrophenol was developed. The biosensor takes advantage of the ability of Moraxella sp. to specifically degrade p-nitrophenol to hydroquinone, a more electroactive compound than p-nitrophenol. The electrochemical oxidation current of hydroquinone formed in biodegradation of p-nitrophenol was measured at Moraxella sp.-modified carbon paste electrode and correlated to p-phenol concentrations. The optimum response was realized by electrode constructed using 15 mg of dry cell weight per 1 g of carbon paste and operating at 0.3 V (versus Ag/AgCl reference) in pH 7.5, 20 mM sodium phosphate buffer. Operating at these optimum conditions the biosensor had excellent selectivity against phenol derivatives and was able to measure as low as 20 nM (2.78 ppb) p-nitrophenol with very good accuracy and reproducibility. The biosensor was stable for approximately 3 weeks when stored at 4 degrees C. The applicability of the biosensor to measure p-nitrophenol in lake water was demonstrated.


Game induced emotion analysis using electroencephalography.
Organizations vie to develop insights into the psychological aspects of consumer decision-making to enhance their products accordingly. Understanding how emotions and personality traits influence the choices we make is an integral part of product design. In this paper, we have employed machine learning algorithms to profile discrete emotions, in response to video games stimuli, based on features extracted from recorded electroencephalography (EEG) and to understand certain characteristics of personality. Four video games from different genres have been used for emotion elicitation and players' EEG signals are recorded. EEG being a non-stationary, non-linear and extremely noisy signal has been cleaned using a Savitzky-Golay filter which is found to be suitable for single-channel EEG devices. Seven out of sixteen features from time, frequency and time-frequency domains have been selected using Random Forest and used to classify emotions. Support Vector Machine, k-Nearest Neighbour and Gradient Boosted Trees classifiers have been used where the highest classification accuracy 82.26% is achieved with Boosted Trees classifier. Our findings propagate that for a single-channel EEG device, only four discrete emotions (happy, bored, relaxed, stressed) can be classified where two emotions happy and bored achieved the highest individual accuracy of 88.89% and 85.29% respectively with the Gradient Boosted Trees Classifier. In this study, we have also identified personality traits, extroversion and neuroticism influence players' perception of video games. The results indicate that players with low extroversion prefer relatively slow and strategy games as compared to highly extroverted. It has also been identified that puzzle and racing games are well-liked irrespective of the levels of the two personality traits.


The predictability of the Addiction Severity Index criminal justice assessment instrument and future imprisonment: A Swedish registry study with a national sample of adults with risky substance use.
In Sweden, social workers uses the Addiction Severity Index (ASI) as their main assessment tool when assessing individuals with risky substance use (RSU) or substance use disorder. The aim of this study is to identify among individuals with RSU, the associations of ASI Composite Scores (CSs) with future imprisonment controlling for age, education level and gender. Baseline ASI-data was merged with national registry data on prison sentences (2003-2016). Cox regression was used to estimate the associations between CSs for alcohol, drugs other than alcohol, legal, family and social relationships, employment, mental- and physical health and future imprisonment for adults (n = 14,914) assessed for RSU. The regression showed that all ASI CSs, age, education level and gender were significantly associated with imprisonment post ASI base-line assessment. The variables with the strongest association with imprisonment were ASI legal CS, followed by ASI drugs other than alcohol CS, ASI employment CS and being a male. ASI legal score showed the strongest association with imprisonment, with a 6 time increase in likelihood of imprisonment. Given the findings in this study, the strong significant association between ASI legal CS and future imprisonment, it seems as that the ASI-assessment instrument is a reliable and trustworthy assessment tool to use in clinical work. This should motivate social workers and other clinical health professionals to use and rely on the ASI assessment in their intervention planning for clients with RSU, to hopefully reduce future imprisonment and improve their social situation.


[Efficacy and safety of a single intra-articular injection of 2% hyaluronic acid plus mannitol in knee osteoarthritis over a 6-month period].
To evaluate the safety and efficacy of a single intra-articular injection of 2% hyaluronic acid (HA)+mannitol in symptomatic knee osteoarthritis (KOA). Pilot, multicentre, open, non-comparative study performed in eighty patients with painful KOA, of whom 79 completed the study. They received one injection of 2ml of 2% HA+0.5% mannitol (Day 0) and were followed-up for 6 months. On Days 0, 15, 30, 60, 90, 120, 150 and 180, pain and joint function were assessed using a visual analogue scale (VAS) and WOMAC index. Efficacy and safety by investigator and patient, and rescue medication, as an indirect measure of pain, were also recorded. A significant reduction in joint pain, stiffness and functional disability compared with baseline was observed at every follow-up visit (P<.001). Joint function improved by 38.7% on Day 30, reaching 47.5% on Day 180. Rescue medication use decreased from 58.2% at baseline to 2.5% on Day 90, increasing in the last visits. Efficacy and safety were positively evaluated by investigators and patients. No serious adverse events were observed. Mild side effects were reported in 4 patients (local pain and swelling in the infiltration area). There is evidence that repeated intra-articular injections of HA improve symptoms in KOA. However, studies with a single injection of HA have shown mixed results. This study demonstrates that one single intra-articular injection of non-cross-linked HA reduces joint pain and increases function in patients with KOA over a period of at least 6 months.


[Clubbed fingers and arthralgia as a reversible paraneoplastic syndrome (Pierre-Marie-Bamberger syndrome) in non-small-cell bronchial carcinoma].
During chemotherapy for a non-small-cell bronchial carcinoma with metastasis to the right femur (previously locally excised), a 34-year-old man suddenly developed severe, lasting joint pain in the ankle, knee, elbow and wrist without signs of increased warmth or swelling of these joints. At the time of diagnosis clubbed fingers had been noted. Radiography of the hands showed bilateral periosteal hyperostoses. Computed tomography of the thorax revealed tumor progression. The triad of clubbed fingers, periosteal hyperostoses and arthralgia/arthritis with the pulmonary findings established the diagnosis of hypertrophic pulmonary osteoarthritis (HPO; Marie-Bamberger syndrome). Initially there had merely been the signs of the much more frequent incomplete form with only the clubbed fingers, the complete form developing with progression of the disease during chemotherapy, joint pains dominating the symptoms. After right upper lobectomy (primary adenocarcinoma) the joint pains ceased and the finger clubbing regressed. Only 10% of non-small-cell bronchial carcinomas are associated with HPO. Conversely, such a tumor is found in 90% of HPO of recent onset and should therefore be sought of when searching for the primary tumor. The signs of HPO are reversible if the underlying disease is adequately treated.


Sexual Difference in the Optimum Environmental Conditions for Growth and Maturation of the Brown Alga Undaria pinnatifida in the Gametophyte Stage.
Undaria pinnatifida is an annual brown kelp growing naturally in coastal areas as a major primary producer in temperate regions and is cultivated on an industrial scale. Kelps have a heteromorphic life cycle characterized by a macroscopic sporophyte and microscopic sexual gametophytes. The sex-dependent effects of different environmental factors on the growth and maturation characteristics of the gametophyte stage were investigated using response surface methodology. Gametophytes were taken from three sites in Japan: Iwate Prefecture, Tokushima Prefecture, and Kagoshima Prefecture in order to confirm the sexual differences in three independent lines. Optimum temperature and light intensity were higher for males (20.7-20.9 °C and 28.6-33.7 µmol m-2 s-1, respectively) than females (16.5-19.8 °C and 26.9-32.5 µmol m-2 s-1), and maturity progressed more quickly in males than females. Optimum wavelengths of light for growth and maturation of the gametophytes were observed for both blue (400-500 nm, λmax 453 nm) and green (500-600 nm; λmax 525 nm) lights and were sex-independent. These characteristics were consistent among the three regional lines. Slower growth optima and progress of maturation could be important for female gametophytes to restrict fertilization and sporophyte germination to the lower water temperatures of autumn and winter, and suggest that the female gametophyte may be more sensitive to temperature than the male. The sexual differences in sensitivity to environmental factors improved the synchronicity of sporeling production.


Can infectious modelling be applicable globally - lessons from COVID 19.
Contagious diseases are needed to be monitored to prevent spreading within communities. Timely advice and predictions are necessary to overcome the consequences of those epidemics. Currently, emphasis has been placed on computer modelling to achieve the needed forecasts, the best example being the COVID-19 pandemic. Scientists used various models to determine how diverse sociodemographic factors correlated and influenced COVID-19 Global transmission and demonstrated the utility of computer models as tools in disease management. However, as modelling is done with assumptions with set rules, calculating uncertainty quantification is essential in infectious modelling when reporting the results and trustfully describing the limitations. This article summarizes the infectious disease modelling strategies, challenges, and global applicability by focusing on the COVID-19 pandemic.


Prevalence of CT-detected cerebral abnormalities in an elderly Swedish population sample.
To measure the prevalence of computed tomography (CT)-detected cerebral lesions in a population-based sample of elderly persons living in Göteborg, Sweden. Cerebral CT-scans were performed in the case of 466 women (mean age 74.3 +/- 5.1 years) and 191 70-year-old men. A single rater assessed white matter lesions (WML) using four different scales, lacunar lesions, large infarcts, cortical atrophy, and basal ganglia calcifications. White matter lesions frequency assessed by different scales ranged between 54.5% and 68.5%. Lacunar lesions were detected in 46.7% (30.1% had lacunes >5 mm) and cerebral infarcts in 3.0% of participants. Overall, 72.8% of participants evidenced cerebral vascular abnormalities. Severe cortical atrophy was more common in temporal (6.4%) and frontal (6.7%) lobes, than in parietal (1.7%) and occipital (1.1%) lobes. Basal ganglia calcifications were found in 38.7% of participants. WML, lacunar lesions, large infarcts, and degree of cortical atrophy correlated positively with age. More lacunes, basal ganglia calcifications, and occipital lobe atrophy were associated with male gender. Vascular and other brain lesions are very common on CT-scan in an elderly population, but large vascular lesions are rare. This study provides the first reference for the prevalence of CT-detected abnormalities in an elderly Swedish population.


Association of asthma with obesity among adolescents exposed to environmental tobacco smoke.
The purpose of this study was to examine the association between asthma diagnosis and obesity among adolescents exposed to environmental tobacco smoke (ETS). The sample included 28,807 adolescents (13-17 years old) from the National Survey of Children's Health (NSCH) (2011-2012). The NSCH is a US cross-sectional telephone survey that included at least one child between the ages of 0 and 17 years residing at a household during the time of the interview. Descriptive statistics were used to describe sample characteristics and assess the prevalence of asthma among adolescents with obesity exposed to ETS. Logistic regression models were built to assess the effect of obesity on asthma diagnosis within the context of ETS exposure. The prevalence of asthma among adolescents was 10.4% and the obesity was 13.2%. Adolescents with obesity exposed to ETS within the home were significantly (p < 0.05) more likely to have an asthma diagnosis (23%) compared with non-obese (10.9%) residing in similar households. Adjusted odds ratios showed that adolescents with obesity were 2.07 (95% CI, 1.15, 3.70) times more likely to have asthma if they were exposed to ETS inside their homes. The findings indicate that adolescents with obesity are more likely to be diagnosed with asthma if they are exposed to ETS in the household. It is important that the association between obesity and asthma is examined within the context of environmental risk factors in future studies, as this may shed some light to underlying mechanisms between these two serious public health issues.


Mortality after ischemic stroke in patients with acute myocardial infarction: predictors and trends over time in Sweden.
Acute myocardial infarction (AMI) increases the risk of ischemic stroke, and mortality among these patients is high. Here, we aimed to estimate the 1-year mortality reliably after AMI complicated by ischemic stroke. We also aimed to identify trends over time for mortality during 1998-2008, as well as factors that predicted increased or decreased mortality. Data for 173 233 unselected patients with AMI were collected from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions registry for 1998-2008. Specifically, we analyzed 1-year follow-up and mortality data for patients with AMI with and without ischemic stroke. Kaplan-Meyer analysis was used to analyze mortality trends over time, and Cox regression analysis was used to identify uni- and multivariate predictors of mortality. The 1-year mortality was 36.5% for AMI complicated by ischemic stroke and 18.3% for AMI without stroke. Mortality decreased over time in patients with and without ischemic stroke. The absolute decreases in mortality were 9.4% and 7.5%, respectively. Reperfusion and secondary preventive therapies were associated with a decreased mortality rate. Mortality after AMI complicated by an ischemic stroke is very high but decreased from 1998 to 2008. The increased use of evidence-based therapies explains the improved prognosis.


The spectrum of morphomolecular abnormalities of the E-cadherin/catenin complex in pleomorphic lobular carcinoma of the breast.
Pleomorphic lobular carcinoma of the breast is a high nuclear grade variant of lobular carcinoma. E-cadherin, a tumor-invasion suppressor gene, codes for a transmembrane protein that functions in intercellular adhesion. The E-cadherin protein internal domain binds with alpha, beta, gamma, and p120 catenins to anchor the E-cadherin complex to the actin cytoskeleton of the cell. The E-cadherin gene is routinely mutated in lobular neoplasia. This study examines the morphomolecular spectrum of the components of the E-cadherin-catenin complex in lobular neoplasia. Fifteen cases of pleomorphic lobular neoplasia, 8 cases of classic lobular neoplasia and 4 ductal carcinomas were studied. Normal breast epithelium and invasive ductal carcinomas all showed intense linear cell membrane immunostaining with antibodies to E-cadherin, alpha, beta, gamma, and P120 catenins. Membrane immunostaining of the catenin antibodies in lobular neoplasia was negative, except for rare cases that displayed beaded or dotlike patterns. Cytoplasmic immunostaining patterns for all lobular lesions included coarse paranuclear granules of beta catenin or diffuse intense cytoplasmic staining for P120 catenin. These immunostaining patterns demonstrate that catenins alpha, beta, gamma, and p120 are routinely dislocated from the cell membrane into the cytoplasm in lobular neoplasia and that the disrupted catenin patterns parallel absence of membrane E-cadherin in all cases. The diffuse cytoplasmic immunostaining of p120 in lobular neoplasia may be useful diagnostically as a positive marker for lobular neoplasia.


Reversible two-step unfolding of heme-human serum albumin: a (1)H-NMR relaxometric and circular dichroism study.
Human serum albumin (HSA) participates in heme scavenging, the bound heme turning out to be a reactivity center and a powerful spectroscopic probe. Here, the reversible unfolding of heme-HSA has been investigated by (1)H-NMR relaxometry, circular dichroism, and absorption spectroscopy. In the presence of 6 equiv of myristate (thus fully saturating all available fatty acid binding sites in serum heme-albumin), 1.0 M guanidinium chloride induces some unfolding of heme-HSA, leading to the formation of a folding intermediate; this species is characterized by increased relaxivity and enhanced dichroism signal in the Soret region, suggesting a more compact heme pocket conformation. Heme binds to the folding intermediate with K (d) = (1.2 +/- 0.1) x 10(-6) M. In the absence of myristate, the conformation of the folding intermediate state is destabilized and heme binding is weakened [K (d) = (3.4 +/- 0.1) x 10(-5) M]. Further addition of guanidinium chloride (up to 5 M) brings about the usual denaturation process. In conclusion, myristate protects HSA from unfolding, stabilizing a folding intermediate state in equilibrium with the native and the fully unfolded protein, envisaging a two-step unfolding pathway for heme-HSA in the presence of myristate.


Predictive Performance of Serum S100B Versus LDH in Melanoma Patients: A Systematic Review and Meta-Analysis.
Currently, no consensus on the use of blood tests for monitoring disease recurrence in patients with resected melanoma exists. The only meta-analysis conducted in 2008 found that elevated serum S100B levels were associated with significantly worse survival in melanoma patients. Serum LDH is an established prognostic factor in patients with advanced melanoma. To compare the discriminative and prognostic ability of serum S100B with that of serum LDH in patients with melanoma. This systematic review and meta-analysis were reported in accordance with the PRISMA Statement. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42019137138). A quantitative analysis of data from 6 eligible studies included 1,033 patients with cutaneous melanoma. The discriminative ability of serum S100B at identifying disease relapse [pooled Area Under the ROC (AUROC) 78.64 (95% CI 70.28; 87.01)] was significantly greater than the discriminative ability of serum LDH [AUROC 64.41 (95% CI 56.05; 7278)] (p=0.013). Ten eligible studies with 1,987 patients were included in the risk of death analysis. The prognostic performance of serum S100B [pooled estimate of adjusted hazard ratio (HR) 1.78 (95% CI 1.38; 2.29)] was independent but not superior to that of serum LDH [HR 1.60 (95% CI 1.36; 2.29)]. A relatively small number of articles were eligible and there was considerable heterogeneity across the included studies. Serum biomarkers may provide relevant information on melanoma patient status and should be further researched. Serum S100B is a valid marker for diagnosis of melanoma recurrence. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42019137138).


Comparative evaluation of post-column free radical scavenging and ferric reducing antioxidant power assays for screening of antioxidants in strawberries.
ABTS and FRAP post-column techniques evaluate the antioxidant characteristics of HPLC separated compounds with specific reagents. ABTS characterize their ability to scavenge free radicals by electron-donating antioxidants, resulting in the absorbance decrease of the chromophoric radical. FRAP - is based on the reduction of Fe(III)-tripyridyltriazine complex to Fe(II)-tripyridyltriazine at low pH by electron-donating antioxidants, resulting in an absorbance increase. Both post-column assays were evaluated and compared according to the following validation parameters: specificity, precision, limit of detection (LoD), limit of quantitation (LoQ) and linearity. ABTS and FRAP post-column assays were specific, repeatable and sensitive and thus can be used for the evaluation of antioxidant active compounds. Antioxidant active compounds were quantified according to TEAC for each assay and ABTS/FRAP ratio was derived. No previous records of antioxidative activity of leaves and fruits of strawberries (Fragaria viridis, Fragaria moschata) research have been found. The research results confirm the reliability of ABTS and FRAP post-column assays for screening of antioxidants in complex mixtures and the determination of radical scavenging and ferric reducing ability by their TEAC values.


Hammock anastomosis: a nonrefluxing ureteroileal anastomosis.
During a 9-year period diversion was performed in 48 patients by an antireflux ureteroileal anastomosis. Followup was possible in 30 patients (57 renal units). Among these 57 ureteroileal anastomoses only 3 cases of stenosis (6 per cent) and 11 cases of reflux (less than 20 per cent) were observed. These results are roughly comparable to those with colon conduits. The 30 patients included 2 in whom the antireflux anastomosis formed part of a continent ileal stoma. The method is described and the results are discussed.


Small intestinal transit, bacterial growth, and bowel habits in diabetes mellitus.
To investigate diabetic alterations of small intestinal transit and bacterial growth, we performed hydrogen breath tests (10 g lactulose via duodenal tube at the ligament of Treitz), bacterial cultures, and determinations of unconjugated serum bile acids in 19 patients with long-standing diabetes and 7 healthy controls. Asymptomatic diabetics had a late rise in breath hydrogen, indicating prolonged jejunal-cecal transit (86 +/- 10 min, p less than 0.05) as an early pathogenic event. Rise in breath hydrogen in symptomatic diabetics (constipation: 50 +/- 6 min; diarrhea: 41 +/- 11 min) was not significantly different from controls (57 +/- 8 min). Bacterial studies and increased unconjugated serum bile acids suggest bacterial overgrowth in some symptomatic diabetics. Bacterial overgrowth was associated more frequently (p less than 0.05) with a rise in breath hydrogen before 45 min or after 75 min. Changes in the hydrogen breath test, bacterial growth, or unconjugated serum bile acids did not correlate with gastrointestinal symptoms of diabetes.


A quantitative method to discriminate between non-specific and specific lectin-glycan interactions on silicon-modified surfaces.
Essential to the success of any surface-based carbohydrate biochip technology is that interactions of the particular interface with the target protein be reliable and reproducible and not susceptible to unwanted nonspecific adsorption events. This condition is particularly important when the technology is intended for the evaluation of low-affinity interactions such as those typically encountered between lectins and their monomeric glycan ligands. In this paper, we describe the fabrication of glycan (mannoside and lactoside) monolayers immobilized on hydrogenated crystalline silicon (111) surfaces. An efficient conjugation protocol featuring a key "click"-based coupling step has been developed which ensures the obtention of interfaces with controlled glycan density. The adsorption behavior of these newly developed interfaces with the lectins, Lens culinaris and Peanut agglutinin, has been probed using quantitative IR-ATR and the data interpreted using various isothermal models. The analysis reveals that protein physisorption to the interface is more prevalent than specific chemisorption for the majority of washing protocols investigated. Physisorption can be greatly suppressed through application of a strong surfactinated rinse. The coexistence of chemisorption and physisorption processes is further demonstrated by quantification of the amounts of adsorbed proteins distributed on the surface, in correlation with the results obtained by atomic force microscopy (AFM). Taken together, the data demonstrates that the nonspecific adsorption of proteins to these glycan-terminated surfaces can be effectively eliminated through the proper control of the chemical structure of the surface monolayer combined with the implementation of an appropriate surface-rinse protocol.


Herpesvirus and adenovirus surveillance in threatened wild West Indian (Trichechus manatus) and Amazonian manatees (Trichechus inunguis), Brazil.
African (Trichechus senegalenses), West Indian (T. manatus), WIM)], and the Amazonian manatees (T. inunguis, AMM). Whereas WIM inhabits both riverine and coastal systems in the western Atlantic, AMM is the only exclusively freshwater sirenian, endemic to the Amazon River Basin. The study of infectious agents is essential to species conservation, especially considering that both species are classified as Vulnerable by the IUCN Red List and as Endangered by the Brazilian Red List. The current knowledge about viral agents in sirenians is scarce. Herpesviruses and adenovirus are DNA viruses able to infect and cause disease in a wide range of hosts. Herein, we used panPCR protocols to survey herpesvirus and adenovirus in blood samples of wild WIM (n = 23) and AMM (n = 26) under human care in Brazil. Herpesvirus DNA was detected in one juvenile female WIM (1/23; 4.3%; 95% CI -4.7 - 13.3) from Ceará state and in four AMM (two juvenile females, a juvenile male, and an adult female; 4/26; 15.4%; 95% CI 0.5 - 30.3) from Amazonas state. The two different gammaherpesvirus DNA polymerase sequence types identified (one per species, a sequence type in a WIM and another one in three AMM) were highly similar (99% nucleotide identity) to Trichechid herpesvirus 1, reported in West Indian manatees of Florida (USA), and 100% identical when translated into amino acids. A herpesviral glycoprotein B sequence was identified in two AMM. None of the samples was positive to adenovirus. To the authors' knowledge, this is the first herpesvirus detection in manatees from South America, expanding the herpesvirus geographical range, and the first in WIM and AMM worldwide. Our findings suggest (i) that West Indian and Amazonian manatees are possibly the natural hosts of the detected herpesvirus, and (ii) coevolution of that gammaherpesvirus with Trichechus. Future studies are necessary to characterize the obtained virus and elucidate potential pathological effects (if any) in these species.


Erythema Nodosum Induced by the Pfizer- BioNTech Vaccine.
A 42-year-old man presented with a painful nodular dermatitis with 38.5°C fever and joint pain, which started overnight. The patient had taken the first dose of Pfizer-BioNTech (Comirnaty, INN-COVID-19 mRNA) vaccine 8 days ago. He denied any kind of recent infections, inflammatory conditions, malignancies, or drugs administration.


A study of association between expression of hOGG1, VDAC1, HK-2 and cervical carcinoma.
Human 8-oguanine glycosylase 1(hOGG1), voltage-dependent anion channel 1(VDAC1), hexokinase 2(HK-2), represented the process of oxidative DNA damage, cell apoptosis and glycolysis, respectively. This study aims to explore the association between expression of hOGG1, VDAC1, HK-2 and cervical carcinoma. A case-control study was conducted. 65 cervical biopsy samples consist of 20 control and 45 cases. The expression of hOGG1, VDAC1 and HK-2 were examined with immunohistochemistry(IHC), immunolabeling was evaluated with stereological cell counts. The data showed that the positive proportion of hOGG1 and HK-2 in the case group was higher than that of the control group (P < 0.05). Further, there was an increasing trend for the positive proportion and expression degree of hOGG1 and HK-2 from Control, Mild cervical carcinoma (MCC), Intermediate cervical carcinoma(ICC) to Severe cervical carcinoma(SCC) in order (P < 0.05). To VDAC1, the significant result was not obtained. The results suggested that there was a close association between expression of hOGG1, HK-2 and cervical cancer. hOGG1 and HK-2 might play a key role at the early stage of cervical cancer, and the findings of hOGG1 and HK-2 should be considered as a significant biomarker at the early stage of cervical cancer.


3-Pyridyloxypropanolamine agonists of the beta 3 adrenergic receptor with improved pharmacokinetic properties.
Pyridyloxypropanolamines L-749,372 (8, beta 3 EC50 = 3.6 nM) and L-750,355 (29, beta 3 EC50 = 13 nM) are selective partial agonists of the human receptor, with 33% and 49% activation, respectively. Both stimulate lipolysis in rhesus monkeys (ED50 = 2 and 0.8 mg/kg, respectively), with minimal effects on heart rate. Oral bioavailability in dogs, 41% for L-749,372 and 47% for L-750,355, is improved relative to phenol analogs.


[Triple nerve block for ambulatory knee arthroscopy].
The purpose of this study was to evaluate intra- and postoperative conditions of the triple nerve block technique (femoral, obturator, sciatic block) for outpatient knee arthroscopic procedures. After written informed consent, ASA I-III patients received a combined triple nerve block with 30-40 ml lidocaine or mepivacaine (1,5%). Blocks were performed using a nerve stimulation technique. Onset time, block failure, supplemental general anesthesia (GA) or analgesia and pain score were recorded intraoperatively. After surgery, side effects (at days 0, 1, 3, 7 and after 4 weeks), patient and surgeon satisfactions were noted. Three hundred and twelve patients were screened and 115 triple blocks were performed (157 chose GA, 19 spinal anaesthesia, 21 exclusion for regional anaesthesia). Failed blocks occurred for 12 (10%) patients. These 12 patients received GA before surgery incision. Time to complete block was 40 (10-60) min. Supplemental GA was required for 12 patients (12%) due to surgical (n=7, 7%) or tourniquet (n=5, 5%) pain. Intraoperative surgeon satisfaction was 90 (60-100). After surgery, time to discharge the postoperative care unit was 15 (5-60) min. Pain score at rest (Visual Analog Scale) until six hours was less than 30 /100, without any additional morphine. Two patients (< 2%) failed for ambulatory discharge criteria (no relation with triple block). At day 0, 3, 5% patients suffered PONV (8% at D1), paresthesia was noted in 1.7% at D0 (0,8% D3). No other secondary effects were observed after seven days and 91% patients "would like same anaesthesia" for next surgery. We conclude that triple nerve block provided reliable intraoperative patient and surgical conditions for outpatient knee arthroscopy. Failed block (10%) was the major reason of supplemental anaesthesia. To increase surgical turn over under triple nerve block, a preoperative room may be required (block onset time).


Digital radiology. Facts and fictions.
Dental digital radiology is a rapidly changing field. The advantages and disadvantages are presented with an understanding that attention to fundamentals is paramount. The message for the near future is cautious optimism.


High plasma levels of N-terminal pro-atrial natriuretic peptide associated with low anxiety in severe heart failure.
Plasma levels of natriuretic peptides are elevated in congestive heart failure (CHF). These peptides show anxiolytic properties in studies of rodents and patients with panic disorder, but their possible effect on anxiety has never been studied in cardiac patients. We therefore assessed associations of the Atrial Natriuretic Pro-Peptide (pro-ANP) with anxiety in patients with CHF and controls. This was a cross-sectional study of 119 patients (46 with CHF, 76 controls with cardiovascular risk factors) in a tertiary care center. The study included assessment of CHF severity, ejection fraction, pro-ANP (microtiter assay), and psychosocial status (self-rating questionnaires for anxiety, depression, vital exhaustion, and quality of life). The diagnosis and severity of CHF was significantly related to pro-ANP levels, bad physical quality of life, vital exhaustion, and depression. However, there was no significant effect of disease severity on anxiety. In CHF patients, pro-ANP was negatively correlated with anxiety (rho = -0.30, p =.041). In the whole group, anxiety was independently predicted by vital exhaustion, depression, and younger age (overall adjusted R2 = 0.48). Pro-ANP plasma levels showed an additional, inverse association with anxiety (beta = -0.17, p =.013, adjusted R2 = 0.50). Predicted mean anxiety scores derived from this model showed a good fit with anxiety scores observed in subgroups defined by CHF severity. Pro-ANP plasma levels are independently and inversely related to anxiety. Even in severe CHF with severely compromised quality of life, anxiety tends to decrease with high pro-ANP levels. This might be part of a negative feedback loop limiting psychological distress and its adverse autonomic consequences in severe heart failure.


Improved quality and information in thyroid scintigraphy.
We compared rectilinear scanning, analogous gamma-camera imaging and imaging using a gamma camera interfaced to a computer in order to determine which of these techniques is superior for thyroid scintigraphy. Forty patients with and without goitre and irregular activity distribution were imaged using each of the three techniques. The sets of three scintigrams per patient were rated by seven physicians. These ratings were statistically analysed using a new distribution-free test. Thyroid scintigraphy using a gamma camera interfaced to a computer turned out to be the best method, especially for detecting circumscribed areas of increased uptake. We conclude that this was due to a combination of the following factors: a computer matrix of 128 X 128 pixels in combination with an acquisition zoom of 1.5, the high count density of the scintigrams, computer-controlled documentation after data acquisition and the use of a continuous grey scale for documentation. The improved quality and information content of the scintigrams obtained using a gamma-camera/computer system could improve the diagnostic value of thyroid scintigraphy, especially when the scintigrams are also evaluated quantitatively.


Irish and New Zealand Midwives' expertise at preserving the perineum intact (the MEPPI study): Perspectives on preparations for birth.
perineal trauma during birth can result in short or long term morbidity for women. Internationally, rates of episiotomy and severe perineal tears vary considerably. In New Zealand, in 2011, and in a trial of midwife-led care in Ireland, episiotomy rates were found to be considerably lower than those in many other countries. A qualitative exploratory study was undertaken to ascertain how midwives achieve these low rates, in these countries and settings. a qualitative exploratory study was conducted. Midwives expert in preserving the perineum intact (PPI) from two maternity units in the Republic of Ireland and from varied birth settings in New Zealand, were eligible to participate. Twenty-one consenting midwives took part, seven from Ireland and 14 from New Zealand. university ethical approval was granted. Face-to-face, semi-structured interviews were used to collect the data. Interviews were recorded and transcribed verbatim. The data were analysed using Ethnograph software and were organised into prominent themes. four themes were identified; 'Sources of knowledge for PPI', 'Associated factors', 'Decision-making on episiotomy', and 'Preparations for PPI'. Participants drew heavily on multiple sources of knowledge in building their own expertise for PPI. Physical characteristics of the perineum featured prominently as factors leading to PPI. Episiotomy was, in the main, only performed when there were signs of fetal distress. Antenatal perineal massage was supported. this study provides valuable insight into the views and skills of midwives, with expertise in PPI at birth, adding to the body of evidence on this topic.


A sensitive and selective UPLC-MS/MS method for simultaneous determination of 10 alkaloids from Rhizoma Menispermi in rat plasma and its application to a pharmacokinetic study.
A sensitive and selective liquid chromatography-tandem mass spectrometry method has been developed and validated for simultaneous quantitation of 10 alkaloids (dauricine, daurisoline, N-desmethyldauricine, dauricicoline, dauriporphinoline, bianfugecine, dauricoside, stepholidine, acutumine and acutumidine) from Rhizoma Menispermi in rat plasma. After addition of internal standard (verapamil), plasma samples were pretreated by a single-step protein precipitation with acetonitrile. Chromatographic separation was performed on a Waters BEH C18 column with gradient elution using a mobile phase composed of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.3 mL/min. The analytes were detected without interference in the multiple reaction monitoring (MRM) mode with positive electrospray ionization. The validated method exhibited good linearity over a wide concentration range (r≥0.9914), and the lower limits of quantification were 0.01-5.0 ng/mL for all the analytes. The intra-day and inter-day precisions (RSD) at three different levels were both less than 13.4% and the accuracies (RE) ranged from -12.8% to 13.5%. The mean extraction recoveries of analytes and IS from rat plasma were all more than 77%. The validated method was successfully applied to a comparative pharmacokinetic study of 10 alkaloids in rat plasma after oral administration of Rhizoma Menispermi extract.


Population pharmacokinetics and covariate analysis of Sym004, an antibody mixture against the epidermal growth factor receptor, in subjects with metastatic colorectal cancer and other solid tumors.
Sym004 is an equimolar mixture of two monoclonal antibodies, futuximab and modotuximab, which non-competitively block the epidermal growth factor receptor (EGFR). Sym004 has been clinically tested for treatment of solid tumors. The present work characterizes the non-linear pharmacokinetics (PK) of Sym004 and its constituent antibodies and investigates two types of covariate models for interpreting the interindividual variability of Sym004 exposure. Sym004 serum concentration data from 330 cancer patients participating in four Phase 1 and 2 trials (n = 247 metastatic colorectal cancer, n = 87 various types advanced solid tumors) were pooled for non-linear mixed effects modeling. Dose regimens of 0.4-18 mg/kg Sym004 dosed by i.v. infusion weekly or every 2nd week were explored. The PK profiles for futuximab and modotuximab were parallel, and the parameter values for their population PK models were similar. The PK of Sym004 using the sum of the serum concentrations of futuximab and modotuximab was well captured by a 2-compartment model with parallel linear and saturable, Michaelis-Menten-type elimination. The full covariate model including all plausible covariates included in a single step showed no impact on Sym004 exposure of age, Asian race, renal and hepatic function, tumor type and previous anti-EGFR treatments. The reduced covariate model contained statistically and potentially clinically significant influences of body weight, albumin, sex and baseline tumor size. Population PK modeling and covariate analysis of Sym004 were feasible using the sum of the serum concentrations of the two constituent antibodies. Full and reduced covariate models provided insights into which covariates may be clinically relevant for dose modifications and thus may need further exploration.


A study of the mechanisms of proteinuria in nephritis and chronic renal failure.
This study was carried out on 50 patients suffering from renal disorders; 30 nephritis patients and 20 chronic renal failure patients. Twenty-four healthy persons were used as a control group. In order to cast some light on the degree of the impaired glomerular permeability with respect to the blood proteins, selectivity of proteinuria was assessed by means of the clearance of albumin, ceruloplasmin, transferrin, and haptoglobin. Disturbances in the metabolism of these proteins were observed and discussed in light of the proteinuria selectivity index. The demonstration of the selective proteinuria in the presence of haptoglobin was concluded to be indicative of the degree of impaired glomerular permeability in nephritis and chronic renal failure.


The prevalence and the etiology of the initial dummy- and finger-sucking habit.
The prevalence of dummy- and finger-sucking habits, or malocclusions of the type that may be associated with sucking habits, was examined in three different groups: Group A--415 small children from Mnene, Zimbabwe; group B--20 skulls from the Schreiner Collections, Anatomical Institute, Oslo, exhibiting intact deciduous dentitions. The skulls are mainly from the period A.D. 1000 to 1500 and were found in Scandinavia. Group C consisted of 280 young Swedish children. The study indicates that dummy- and finger-sucking habits occur infrequently among the African children other than as a symptom of a disturbance in the normal feeding and/or care in other respects. The investigation of the medieval skull material supports a similar situation among these Scandinavian children. In Sweden most infants are dummy- or finger-suckers. The authors introduce an explanation for the development of the initial sucking habits.


Therapeutics and prophylactic efficacy of novel lytic Escherichia phage vB_EcoS_PJ16 against multidrug-resistant avian pathogenic E. coli using in vivo study.
Avian pathogenic Escherichia coli (APEC) is the causative agent of avian colibacillosis, which causes significant economic losses to the poultry industry. The growing resistance of bacteria to antibiotics is a major global public health concern. However, there is limited data on the efficacy of phage therapy in effectively controlling and treating APEC infections. In this study, a novel lytic Escherichia phage, vB_EcoS_PJ16, was isolated from poultry farm wastewater and characterized in both in vitro and in vivo conditions. Transmission electron microscopy analysis revealed the presence of an icosahedral head and a long non-contractile tail, classifying the phage under the Caudoviricetes class. Host range determination showed that Escherichia phage vB_EcoS_PJ16 exhibited lytic activity against multiple strains of pathogenic E. coli, while no significant signs of lysis for Klebsiella pneumoniae, Salmonella Typhimurium, Listeria monocytogenes, and Staphylococcus aureus. Biophysical characterization revealed that the isolated phage was sturdy, as it remained viable for up to 300 days at temperatures of 30 °C, 37 °C, and 42 °C and for up to 24 h at pH 5 to 11, with only minor changes in titer. Kinetic analysis at multiplicity of infection (MOI) 0.1 showed a latency period of about 20 min and a burst size of 26.5 phage particles per infected cell for phage vB_EcoS_PJ16. Whole genome sequencing unveiled that the phage vB_EcoS_PJ16 genome consists of a double-stranded linear DNA molecule with 57,756 bp and a GC content of 43.58%. The Escherichia phage vB_EcoS_PJ16 genome consisted of 98 predicted putative ORFs, with no transfer RNA identified in the genome. Among these 98 genes, 34 genes were predicted to have known functions. A significant reduction in APEC viability was observed at MOI 100 during in vitro bacterial challenge tests conducted at different MOIs (0.01, 1, and 100). In vivo oral evaluation of the isolated phage to limit E. coli infections in day-old chicks indicated a decrease in mortality within both the therapeutic (20%) and prophylactic (30%) groups, when compared to the control group. The findings of this study contribute to our current knowledge of Escherichia phages and suggest a potentially effective role of phages in the therapeutic and prophylactic control of antibiotic-resistant APEC strains.


Pro-inflammatory role of transient receptor potential canonical channel 6 in the pathogenesis of chronic rhinosinusitis with nasal polyps.
The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) has not been fully elucidated. This study sought to explore the role and mechanism of transient receptor potential canonical channel 6 (TRPC6) in the pathogenesis of CRSwNP. Immunohistochemistry (IHC) was employed to evaluate TRPC6 immunolabeling. Real-time polymerase chain reaction (PCR) was conducted to assay TRPC6, stromal interaction molecule 1 (STIM1), and calcium release-activated calcium channel protein 1 (Orai1) messenger RNA (mRNA) levels in 70 patients with CRSwNP, including eosinophilic CRSwNP (ECRSwNP) or non-eosinophilic CRSwNP (nECRSwNP), and 28 control subjects. The concentrations of inflammatory mediators, including interleukin (IL)-1β, IL-5, and IL-25, were assayed by enzyme-linked immunosorbent assay (ELISA). In experiments on human nasal epithelial cell (HNEC) culture and stimulation, the mean fluorescence intensity (MFI) of intracellular Ca2+ was assayed by flow cytometry. Western blotting, real-time PCR, and ELISA were also conducted to assess the effects and mechanisms of TRPC6 activator 1-oleoyl-2-acetyl-glycerol (OAG) and TRPC6 inhibitor 1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl) propoxy]ethyl-1H-imidazole (SKF-96365) on HNECs. Upregulation of TRPC6, STIM1, and Orai1 levels was found in CRSwNP patients, particularly in those with ECRSwNP. TRPC6-positive cells correlated positively with the numbers of eosinophils and neutrophils, respectively. Moreover, TRPC6 mRNA was positively correlated with STIM1 and Orai1 mRNA levels. The concentrations of inflammatory mediators, including IL-1β, IL-5, and IL-25, were elevated in CRSwNP, especially in ECRSwNP. In cultured HNECs, TRPC6, STIM1, Orai1, Ca2+ MFI levels, and inflammatory mediators were upregulated by lipopolysaccharide (LPS) and OAG but were inhibited by SKF-96365. TRPC6 plays a pro-inflammatory role in the pathogenesis of CRSwNP via regulating Ca2+ flow.


Association of sustained oxyhemoglobin desaturation and onset of cluster headache attacks.
Ten episodic cluster headache patients in their active cluster period, ten patients in remission and five control subjects were monitored for minute to minute changes in oxygen saturation (SaO2) and pulse rate before and after nitroglycerin (NTG) administration. A transient but significant decrease in SaO2 and increase in pulse rate of 25 minutes duration occurred following NTG in all groups. These changes may reflect physiologic hemodynamic effects of NTG as a smooth muscle relaxant. Subsequently, SaO2 levels and pulse rate recovered to baseline values in remission and control groups. In contrast, SaO2 values in the active cluster group decreased further and after an extended period culminated in cluster headache attacks in 10/10 patients. Three major changes, therefore, distinguished active cluster patients from remission and control groups. First, the magnitude of oxygen desaturation increased after the physiological effects of NTG ceased. Second, oxygen desaturation was sustained for an additional 9 to 30 minutes duration. Third, the hypoxemic state culminated in attacks in all cases. Our findings suggest that the active cluster period may be characterized by an impaired mechanism to autoregulate, and thus compensate, for hypoxemia. It is further proposed that persistence of hypoxemia and the cluster attack onset may share a common mechanism, coupling the two events. We suggest that abnormal central and/or peripheral chemoreceptor activity may be responsible for these events.


Involvement of NF-κB/NLRP3 axis in the progression of aseptic loosening of total joint arthroplasties: a review of molecular mechanisms.
Particulate wear debris can trigger pro-inflammatory bone resorption and result in aseptic loosening. This complication remains major postoperative discomforts and complications for patients who underwent total joint arthroplasty. Recent studies have indicated that wear debris-induced aseptic loosening is associated with the overproduction of pro-inflammatory cytokines. The activation of osteoclasts as a result of inflammatory responses is associated with osteolysis. Moreover, stimulation of inflammatory signaling pathways such as the NF-κB/NLRP3 axis results in the production of pro-inflammatory cytokines. In this review, we first summarized the potential inflammatory mechanisms of wear particle-induced peri-implant osteolysis. Then, the therapeutic approaches, e.g., biological inhibitors, herbal products, and stem cells or their derivatives, with the ability to suppress the inflammatory responses, mainly NF-κB/NLRP3 signaling pathways, were discussed. Based on the results, activation of macrophages following inflammatory stimuli, overproduction of pro-inflammatory cytokines, and subsequent differentiation of osteoclasts in the presence of wear particles lead to bone resorption. The activation of NF-κB/NLRP3 signaling pathways within the macrophages stimulates the production of pro-inflammatory cytokines, e.g., IL-1β, IL-6, and TNF-α. According to in vitro and in vivo studies, novel therapeutics significantly promoted osteogenesis, suppressed osteoclastogenesis, and diminished particle-mediated bone resorption. Conclusively, these findings offer that suppressing pro-inflammatory cytokines by regulating both NF-κB and NLRP3 inflammasome represents a novel approach to attenuate wear-particle-related osteolytic diseases.


Assessing the potential impact of glacial lake outburst floods on individual objects using a high-performance hydrodynamic model and open-source data.
Glacial lake outburst floods (GLOFs) are one of the major natural hazards in certain populated mountainous areas, e.g., the Himalayan region, which may lead to catastrophic consequences including substantial loss of lives. Evaluating the potential socio-economic impact of GLOFs is essential for risk mitigation and enhancing community resilience. Yet in most of the cases, this is confronted with the challenges of limited availability of data and inaccessibility to most of the glacial lakes in the high-altitude areas. This study aims to exploit open data from different sources and high-performance hydrodynamic modelling to develop a new framework for GLOF exposure and impact assessment. In the new framework, different GLOF scenarios are created using a simple dam breach model. A high-performance hydrodynamic model is then adopted to simulate the resulting flood hydrodynamics. Necessary socio-economic information is collected and processed from multiple sources including OpenStreetMap, Google Earth, and global data products to support exposure analysis. Established depth-damage curves are used to assess the GLOF damage extents to different exposed objects and an existing fatality estimating procedure is adopted to assess the potential loss of lives. The evaluation framework is applied to the Tsho Rolpa glacial lake in Nepal. From the results, the worst GLOF scenario as considered can potentially inundate 1647 buildings, impact 5038 people and hit 123 key facilities including schools, hospitals, airports, hydropower plants, etc. It may substantially damage 900 buildings, 10.63 km2 of agricultural land and 50.9 km roads and may potentially lead to 45 deaths even if warning is available.


Chronic intussusception in childhood.
A rare case of chronic intussusception is reported. Radiological investigation including ultrasound, CT and barium enema provided the correct diagnosis. Ultrasound revealed a solid mass near the transverse colon in the right lower abdomen. CT demonstrated the real nature of the solid mass as being the classical 'coiled spring' of intussusception. The barium enema was unsuccessful as an attempt at hydrostatic reduction, but confirmed the diagnosis by a 'crescent-shaped' filling defect in the ascending colon. The patient was discharged after an uneventful surgery and recovery. No organic lesion that precipitated the chronic intussusception was discovered at operation. Radiological findings, the typical clinical picture and adequate treatment are discussed.


Changes in the Recreational Built Environment and Youth Body Mass Index.
Many cities have implemented programs to improve the recreational built environment. We evaluated whether neighborhood recreational built environmental changes are associated with change in body mass index (BMI). We performed a longitudinal assessment of association between the recreational built environment and BMI percent of 95th percentile (BMIp95). Patient data from 2012 to 2017 were collected from electronic medical records including height, weight, sex, race/ethnicity, insurance type, and address. BMIp95 was calculated. Environmental data including sidewalks, trails, Healthy Mile Trails, and parks were collected. Patients' neighborhood environments were characterized using proximity of features from home address. Multilevel linear regressions with multiple encounters per patient estimated effects of recreational features on BMIp95 and stratified models estimated effect differences. Of 8282 total patients, 27.7% were non-Hispanic White, half were insured by Medicaid, and 29.5% changed residence. Median BMIp95 was 86.3%. A decrease in BMIp95 was associated with park proximity in the full cohort (-2.85; 95% CI [confidence interval]: -5.47, -0.24; P = .032), children with obesity at baseline (-6.50; 95% CI: -12.36, -0.64; P = .030) and privately insured children (-4.77; 95% CI: -9.14, -0.40; P = .032). Healthy Mile Trails were associated with an increase in BMIp95 among children without obesity (1.00; 95% CI 0.11, 1.89; P = .027) and children living in higher income areas (6.43; 95% CI: 0.23, 12.64; P = .042). Differences in effect indicate that built environment changes may improve or exacerbate disparities. Improving obesity disparities may require addressing family-level barriers to the use of recreational features in addition to proximity.


An improved method for the bromination of metalated haloarenes via lithium, zinc transmetalation: a convenient synthesis of 1,2-dibromoarenes.
A facile protocol for the synthesis of 1,2-dibromoarenes is described. A standard ortho-lithiation/bromination procedure, when applied to bromoarenes, resulted in poor yields of the corresponding 1,2-dibromoarenes (13-62% yield). However, transmetalation of the transient aryllithium intermediate to an arylzinc species with ZnCl2, followed by bromination, resulted in dramatically improved yields of the synthetically useful 1,2-dibromoarenes (68-95% yield).


Altered thymocyte development observed in EphA4-deficient mice courses with changes in both thymic epithelial and extracellular matrix organization.
Eph receptors and their ligands, Ephrins, are involved in the thymocyte-thymic epithelial cell (TEC) interactions, key for the functional maturation of both thymocytes and thymic epithelium. Several years ago, we reported that the lack of EphA4, a Eph of the subfamily A, coursed with reduced proportions of double positive (DP) thymocytes apparently due to an altered thymic epithelial stroma [Munoz et al. in J Immunol 177:804-813, 2006]. In the present study, we reevaluate the lymphoid, epithelial, and extracellular matrix (ECM) phenotype of EphA4-/- mice grouped into three categories with respect to their proportions of DP thymocytes. Our results demonstrate a profound hypocellularity, specific alterations of T cell differentiation that affected not only DP thymocytes, but also double negative and single positive T cell subsets, as well as the proportions of positively and negatively selected thymocytes. In correlation, thymic histological organization changed markedly, especially in the cortex, as well as the proportions of both Ly51+UEA-1- cortical TECs and Ly51-UEA-1+ medullary TECs. The alterations observed in the expression of ECM components (Fibronectin, Laminin, Collagen IV), integrin receptors (VLA-4, VLA-6), chemokines (CXCL12, CCL25, CCL21) and their receptors (CXCR4, CCR7, CCR9) and in vitro transwell assays on the capacity of migration of WT and mutant thymocytes suggest that the lack of EphA4 alters T-cell differentiation by presumably affecting cell adhesion between TECs and T-TEC interactions rather than by thymocyte migration.


Evidence of Superior and Inferior Sinoatrial Nodes in the Mammalian Heart.
This study sought to investigate the shift of leading pacemaker locations in healthy and failing mammalian hearts over the entire range of physiological heart rates (HRs), and to molecularly characterize spatial regions of spontaneous activity. A normal heartbeat originates as an action potential in a group of pacemaker cells known as the sinoatrial node (SAN), located near the superior vena cava. HRs and the anatomical site of origin of pacemaker activity in the adult heart are known to dynamically change in response to various physiological inputs, yet the mechanism of this pacemaker shift is not well understood. Optical mapping was applied to ex vivo rat and human isolated right atrial tissues, and HRs were modulated with acetylcholine and isoproterenol. RNA sequencing was performed on tissue areas that elicited spontaneous activity, and comparisons were made to neighboring myocardial tissues. Functional and molecular evidence identified and confirmed the presence of 2 competing right atrial pacemakers localized near the superior vena cava and the inferior vena cava-the superior SAN (sSAN) and inferior SAN (iSAN), respectively-which preferentially control the fast and slow HRs. Both of these regions were evident in non-failing rat and human hearts and maintained spontaneous activity in the rat heart when physically separated from one another. Molecular analysis of these 2 pacemaker regions revealed unique but similar transcriptional profiles, suggesting iSAN dominance when the sSAN is silent. The presence of 2 spatially distinct dominant pacemakers, sSAN and iSAN, in the mammalian heart clarifies previous identification of migrating pacemakers and corresponding changes in P-wave morphology in mammalian species.


Effect of ethionine on the rough endoplasmic reticulum from male and female rat liver.
Ethionine causes a decrease in the amount of rough endoplasmic reticulum in rat liver, the effect being greater in female than in male rats. Rough endoplasmic reticulum isolated from rat liver 24 hr after ethionine injection and stripped of its ribosomes partially lost its in vitro ribosome binding capacity. However, no differences were detected between the binding affinities of ribosomes, isolated from either untreated animals or intoxicated rats, to stripped rough membranes derived from normal rats. Structural changes occur in the rough endoplasmic reticulum of the ethionine treated rats, while the ribosomes are still bound to the membrane.


Hemiparkinsonian rats rotate toward the side with the weaker dopaminergic neurotransmission.
Rats with unilateral lesion of the substantia nigra pars compacta (SNpc) have been used as a model of Parkinson's disease. Depending on the lesion protocol and on the drug challenge, these rats rotate in opposite directions. The aim of the present study was to propose a model to explain how critical factors determine the direction of these turns. Unilateral lesion of the SNpc was induced with 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Separate analysis showed that neither the type of neurotoxin nor the site of lesion along the nigrostriatal pathway was able to predict the direction of the turns these rats made after they were challenged with apomorphine. However, the combination of these two factors determined the magnitude of the lesion estimated by tyrosine-hydroxylase immunohistochemistry and HPLC-ED measurement of striatal dopamine. Very small lesions did not cause turns, medium-size lesions caused ipsiversive turns, and large lesions caused contraversive turns. Large-size SNpc lesions resulted in an increased binding of [(3)H]raclopride to D2 receptors, while medium-size lesions reduced the binding of [(3)H]SCH-23390 D1 receptors in the ipsilateral striatum. These results are coherent with the model proposing that after challenged with a dopamine receptor agonist, unilaterally SNpc-lesioned rats rotate toward the side with the weaker activation of dopamine receptors. This activation is weaker on the lesioned side in animals with small SNpc lesions due to the loss of dopamine, but stronger in animals with large lesions due to dopamine receptor supersensitivity.


Energy-efficient electrochemical treatment of paracetamol using a PbO2 anode based on pulse electrodeposition strategy: Kinetics, energy consumption and mechanism.
The purpose of this research is to study the pulse electrochemical oxidation of paracetamol (PCT) using a novel PbO2 anode based on pulse electrodeposition strategy (PbO2-PE). The pulse electrodeposition strategy used to prepare a PbO2 anode resulted in rougher surface, higher directional specificity of β(101) and more redox couples of Pb4+/Pb2+. Additionally, the oxygen evolution potential (OEP) and charge transfer resistance were also improved. When compared to direct current electrochemical oxidation process, pulse electrolysis in had a slightly higher PCT removal efficiency and active species (·OH and active chlorine) production, while 72.04% of energy consumption was saved. The effects of operating parameters on PCT degradation efficiency and specific energy consumption were studied. The findings suggested that the pulse electrochemical oxidation of PCT followed a pseudo-first-order kinetic model, with PCT removal reaching 98.63% after 60 min of electrolysis under optimal conditions. Possible mechanisms describing reaction pathways for PCT were also proposed. Finally, combinating with the economic feasibility and safety evaluation, we could conclude that pulse electrolysis with a PbO2-PE electrode was a promising option for improving the practicability of electrochemical treatment for refractory organic wastewater.


Effect of low light intensity on testicular function in photorefractory domestic ganders.
The seasonal variation of the plasma testosterone level of domestic ganders--living under natural photoperiod in Central Hungary--shows a bimodal rhythmicity. An experimental group of ganders within a photorefractory period was exposed to continuous low light intensity (1 lx/m2) from the middle of July until the beginning of August. They were then kept under natural daylight (14.5 L-9.5 D), and then had extra light (14 L-10 D) until the end of the experiment (end of November). The testis weight and the plasma concentration of testosterone were increased significantly as a result of low light intensity but failed to reach the seasonal (February) peak. Having readjusted the birds to natural photoperiod the testosterone plasma concentration did not continue to increase, but decreased slowly for 44 days (16 September). Between the 44th and 52nd day of the experiment (24 September) the testosterone concentration was reduced to the level of the control animals, which were maintained under natural photoperiod. It was established that the photorefractory period had not been terminated by 3 weeks' low light intensity, but a moderate gonadostimulation had occurred. Since photostimulation did not increase the plasma testosterone, but a superactive LH-RH analog increased it significantly in birds which had been in low light intensity, it is supposed that the cause of the refractoriness in ganders may also be decreased gonadotropin-releasing hormone secretion.


Antibiotics for penetrating abdominal trauma: a prospective comparative trial of single agent cephalosporin therapy versus combination therapy.
In this prospective, comparative study, 129 patients who sustained penetrating abdominal trauma were randomized to receive preoperatively, and for 3-5 days postoperatively, one of three antibiotic regimens: Group I--cefotaxime (CTX) (2 Gm Q8H), Group II--cefoxitin (2 Gm Q6H), or Group III--clindamycin (900 mg Q8H) and gentamicin (3-5 mg/kg/day in divided doses Q8H). The three groups were similar in terms of the following: age, sex, severity of injury, number of organs injured, colon injuries, shock, blood transfusions, or positive intraoperative cultures. Septic complications occurred as follows: Group I--6.9%, Group II--2.3%, and Group III--6.9%. The three regimens ranked as follows in terms of therapy costs: CTX less than cefoxitin less than clindamycin and gentamicin. It is concluded that single agent therapy with a cephalosporin is preferable to combination therapy on the basis of equivalent effectiveness, lower toxicity, and lower costs.


The effect of peri-implantation administration of uterine relaxing agents in assisted reproduction treatment cycles: a systematic review and meta-analysis.
Sub-endometrial junctional zone peristalsis is increased by ovarian stimulation and traumatic embryo transfer, and is linked with decreased implantation and pregnancy rates in assisted reproduction treatments. Various agents have been used to inhibit uterine hyper-peristalsis at the time of embryo transfer with conflicting results. This systematic review aimed to identify if uterine relaxants administered in the peri-implantation period during assisted reproduction treatments could improve pregnancy outcomes through literature search with no language restrictions. The review reports on 3546 patients in 17 randomized controlled trials published between 1993 and 2014. Women undergoing assisted reproduction techniques who either received a uterine relaxant agent in the peri-implantation period versus placebo or no treatment were included. Primary outcome was live birth rate. The meta-analyses did not show statistically significant benefit of any uterine relaxing agents on live birth rate. Other meta-analyses did not show a significant effect on the clinical pregnancy, spontaneous abortion, ectopic pregnancy and multiple pregnancy rate. Most of the included studies were of low quality and lacked significant power to detect minimally important effect. Evidence is insufficient to recommend using these agents in routine practice. Further methodologically robust randomized controlled trials with more refined selection criteria might reveal a beneficial effect.


Pathogenesis of endometriosis: the role of genetics, inflammation and oxidative stress.
Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. The etiology of this multifactorial disease is still unresolved and an increasing number of studies suggest that genetic, hormonal, environmental, immunological and oxidative factors may all play an important role in the pathogenesis of this disorder. In this literature review, inflammatory activity, oxidative stress as well as genetic abnormalities and mutations have been studied in an effort to identify factors predisposing to endometriosis.


γ-Secretase in Alzheimer's disease.
Alzheimer's disease (AD) is caused by synaptic and neuronal loss in the brain. One of the characteristic hallmarks of AD is senile plaques containing amyloid β-peptide (Aβ). Aβ is produced from amyloid precursor protein (APP) by sequential proteolytic cleavages by β-secretase and γ-secretase, and the polymerization of Aβ into amyloid plaques is thought to be a key pathogenic event in AD. Since γ-secretase mediates the final cleavage that liberates Aβ, γ-secretase has been widely studied as a potential drug target for the treatment of AD. γ-Secretase is a transmembrane protein complex containing presenilin, nicastrin, Aph-1, and Pen-2, which are sufficient for γ-secretase activity. γ-Secretase cleaves >140 substrates, including APP and Notch. Previously, γ-secretase inhibitors (GSIs) were shown to cause side effects in clinical trials due to the inhibition of Notch signaling. Therefore, more specific regulation or modulation of γ-secretase is needed. In recent years, γ-secretase modulators (GSMs) have been developed. To modulate γ-secretase and to understand its complex biology, finding the binding sites of GSIs and GSMs on γ-secretase as well as identifying transiently binding γ-secretase modulatory proteins have been of great interest. In this review, decades of findings on γ-secretase in AD are discussed.


Identification of 23 novel MHC class I alleles in cynomolgus macaques of Philippine and Philippine/Mauritius origins.
We report here novel Mafa-A, -AG and -B alleles identified in two groups of cynomolgus macaques.


Restorative retinal laser therapy: Present state and future directions.
Because of complications and side effects, conventional laser therapy has taken a back seat to drugs in the treatment of macular diseases. Despite this, research on new laser modalities remains active. In particular, various approaches are being pursued to preserve and improve retinal structure and function. These include micropulsing, various exposure titration algorithms, and real-time temperature feedback control of short-pulse continuous wave lasers, and ultra-short-pulse nanosecond lasers. Some of these approaches are at the preclinical stage of development, whereas others are available for clinical use. Cell biology is providing important insights into the mechanisms of action of retinal laser treatment. We outline the technological bases of current laser platforms, their basic science, therapeutic concepts, clinical experience, and future directions for retinal laser treatment.


Uncemented metal-on-metal acetabular component: follow-up of 112 hips for a minimum of 5 years.
Aseptic loosening is the major cause of implant failure. In cemented hip arthroplasty, failure of the acetabular side is mainly due to lysis caused by wear particles. By using an implant with low wear characteristics and by enhancing acetabular fixation using an uncemented implant, we aimed to reduce acetabular lysis and thereby loosening. This was a retrospective cohort study of 119 hips (101 patients) that had the Uncemented Fitmore cup (Sulzer Orthopedics). In 66 patients, the femoral component was CF-30 (Sulzer) used with cement. In the remaining 35 patients, thrust plate prosthesis (TPP) (Sulzer) was used. Of the 101 patients, 94 (112 hips) were available for study. Mean follow-up of the 94 patients was 7 (5-13) years. The mean preoperative Harris hip score was 38 and the mean postoperative Harris hip score was 89 at the last follow-up. Taking aseptic loosening as the endpoint, the survival rate of the Fitmore cup was 100% at 11 years. The uncemented Fitmore acetabular cup with second generation metal-on-metal articulation showed good results with regard to aseptic loosening in the medium term.


The impact of splenic weight on laparoscopic splenectomy for splenomegaly.
Enlarged spleens increase the technical difficulties associated with laparoscopic splenectomy (LS). The aim of this study was to analyze the impact of splenic weight on the results of LS. We performed a prospective analysis of 20 LS for splenomegaly and 40 LS for normal spleen in terms of intraoperative and early postoperative outcome. Patients with splenomegaly had longer operative times and higher conversion and transfusion rates than those with normal spleens. Patients with spleens weighing < 2000 G experienced less blood loss, fewer conversions, and a shorter postoperative hospital stay than those with spleens > 2000 g. No differences-except for the longer operative time-were observed between normal-sized spleens and those weighing < 2000 G. LS for splenomegaly is feasible for experienced laparoscopic surgeons. For spleens weighing < 2000 G, the outcome was comparable to that of normal spleens, whereas LS for spleens >2000 g was associated with a higher conversion rate, greater blood loss, a longer hospital stay, and increased morbidity.


The MyotonPRO: A reliable tool for quantifying the viscoelastic properties of a trigger point on the infraspinatus in non-traumatic chronic shoulder pain.
Clinicians rely on palpation for locating and diagnosing trigger points in muscles. Measuring a trigger point with clinical palpation remains a challenge. There are currently no validated tools available in clinical practice to objectively measure a trigger point. The presence of a trigger point within the infraspinatus muscle was identified on thirty-five individuals with non-traumatic chronic shoulder pain via palpation according to Travell and Simons criteria. Trigger and non-trigger points were marked within the same muscle and the viscoelastic properties of both points were independently measured twice with the MyotonPRO by two evaluators on two days. Significant differences were observed when the trigger and non-trigger point (discriminant validity) were compared. The trigger points showed greater tone and stiffness compared to the non-trigger points (tone: 15.30 ± 1.99 Hz vs 13.57 ± 1.76 Hz; stiffness: 270.20 ± 46.96 N/m vs 227.86 ± 43.44 N/m; p < 0.05) and less elasticity (decrement of 1.13 ± 0.21 vs 1.06 ± 0.27; p < 0.05). The reliability of the three viscoelastic properties was found to be excellent for intra- and inter-evaluator reliability (ICC: 0.925-0.984 and 0.918-0.972, respectively) and good to excellent for test-retest reliability (between days) (ICC: 0.770-0.875). The MyotonPRO can differentiate the viscoelastic properties of a trigger point from a non-trigger point. Our findings support the reliability of this myotonometer. This affordable and portable tool can be used to objectively measure viscoelastic properties of trigger points in the infraspinatus.


IL15 combined with Caspy2 provides enhanced therapeutic efficiency against murine malignant neoplasm growth and metastasis.
Interleukin-15 (IL15) is a potential immunotherapeutic treatment for cancer. Caspy2 is an active zebra caspase for inducing apoptosis and immune response in murine tumors. In this study, we aim to evaluate the potential of gene therapy using IL15 and Caspy2 against the murine tumors. Plasmid expressing both Caspy2 and IL15 genes was constructed, encapsulated in DOTAP/cholesterol cationic liposome and injected intratumorally into the mice bearing CT26, B16-F10 and 4T1 carcinoma. We found that coexpression of IL15 and Caspy2 could significant inhibit tumor growth and prolong survival of the mice bearing CT26 or B16F10 tumor. A significant reduction in spontaneous lung metastasis was observed in the 4T1 tumor model. In CT26 model, the mice treated with IL15 and Caspy2 acquired a long-time protective immunity against the parental tumor cell rechallenge. Cytotoxic T lymphocytes and terminal deoxynucleotidyltransferase-mediated nick end labelling assays showed that the combination of capsy2 and IL15 could enhance both the apoptosis and immune response induction, which may account for its extraordinary antitumor effect. Furthermore, we showed that the observed tumor suppression by IL15 and Caspy2 concurred with the Caspy2-mediated downregulation of IL10 and upregulation of interferon-γ and tumor necrosis factor-α. Our results therefore suggested that the combination regimen might be a novel and effective strategy for cancer treatment.


Mothering the Mother: An Educational Program for Nurse-Provided Continuous Labor Support.
Continuous labor support (CLS) is associated with improved outcomes including decreased cesarean birth, increased 5-minute APGAR scores, decreased postpartum depression, and decreased nurse turnover rates. Despite this, CLS is not consistently practiced perhaps due to lack of education regarding the benefits of CLS and nurse staffing levels on birthing units. This article will discuss CLS benefits and implementation of an educational program designed to enhance nursing practice with regard to CLS and an educational program designed to provide five skills to perinatal nurses in order to enhance clinical practice. Pretest and posttests were administered and there was a significant knowledge increase related to nurse-provided CLS (p = .001) after attending the program.