Short-term physical inactivity induces diacylglycerol accumulation and insulin resistance in muscle via lipin1 activation.
Physical inactivity impairs muscle insulin sensitivity. However, its mechanism is unclear. To model physical inactivity, we applied 24-h hind-limb cast immobilization (HCI) to mice with normal or high-fat diet (HFD) and evaluated intramyocellular lipids and the insulin signaling pathway in the soleus muscle. Although 2-wk HFD alone did not alter intramyocellular diacylglycerol (IMDG) accumulation, HCI alone increased it by 1.9-fold and HCI after HFD further increased it by 3.3-fold. Parallel to this, we found increased protein kinase C ε (PKCε) activity, reduced insulin-induced 2-deoxyglucose (2-DOG) uptake, and reduced phosphorylation of insulin receptor β (IRβ) and Akt, key molecules for insulin signaling pathway. Lipin1, which converts phosphatidic acid to diacylglycerol, showed increase of its activity by HCI, and dominant-negative lipin1 expression in muscle prevented HCI-induced IMDG accumulation and impaired insulin-induced 2-DOG uptake. Furthermore, 24-h leg cast immobilization in human increased lipin1 expression. Thus, even short-term immobilization increases IMDG and impairs insulin sensitivity in muscle via enhanced lipin1 activity.NEW & NOTEWORTHY Physical inactivity impairs muscle insulin sensitivity. However, its mechanism is unclear. To model physical inactivity, we applied 24-h hind-limb cast immobilization to mice with normal or high-fat diet and evaluated intramyocellular lipids and the insulin signaling pathway in the soleus muscle. We found that even short-term immobilization increases intramyocellular diacylglycerol and impairs insulin sensitivity in muscle via enhanced lipin1 activity.


Structural and social inequities contribute to pockets of low childhood immunisation in New South Wales, Australia.
Childhood immunisation is a safe and effective way to protect children and communities from serious diseases. In Australia childhood immunisation is generally well accepted with high coverage rates however pockets of low coverage exist. Authors conducted five previous studies in New South Wales which found socio-economic disadvantage, gender inequity, health service access barriers and under-utilisation of immunisation data, rather than ideological opposition, contributed to children's incomplete vaccination. Common findings across those five studies were identified. Additional literature was reviewed using a number of lenses, underpinned by a social determinants of health framework. The lensed approach allowed further exploration of the impact of financial stress, poor mental health, drug and alcohol problems, domestic violence, assumed gender roles, lack of culturally acceptable health care for Indigenous families, geography and changes to immunisation policies on families and how this may have contributed to pockets of low immunisation coverage. Social and structural inequities were revealed. These often contributed to conflicting priorities that meant children's immunisations fell behind. Strategies to address inequities may include reorientation of existing community based child health services to include flexible options such as drop in clinics, outreach services, home visiting and ensuring Indigenous families have access to culturally safe and acceptable services. Assistance with transport would further improve access to services. Better use of immunisation data can aid in the identification of pockets of low coverage and monitor and evaluate service effectiveness. Greater awareness of social and structural barriers and their impact on families can inform the design of tailored strategies that address the needs of disadvantaged children and families. Without efforts to overcome the inequities that contribute to low immunisation coverage, the status quo persists, leaving children and communities at risk of vaccine preventable diseases.


Acute treatment of hyperammonemia by continuous renal replacement therapy in a newborn patient with ornithine transcarbamylase deficiency.
Ornithine transcarbamylase (OTC) deficiency is well known as the most common inherited disorder of the urea cycle, and 1 of the most common causes of hyperammonemia in newborns. We experienced a case of a 3-day-old boy with OTC deficiency who appeared healthy in the first 2 days of life but developed lethargy and seizure soon afterwards. His serum ammonia level was measured as >1700 µg/dL (range, 0 to 45 µg/dL). Continuous renal replacement therapy (CRRT) in the mode of continuous venovenous hemodiafiltration was immediately applied to correct the raised ammonia level. No seizure occurred after the elevated ammonia level was reduced. Therefore, CRRT should be included as 1 of the treatment modalities for newborns with inborn errors of metabolism, especially hyperammonemia. Here, we report 1 case of successful treatment of hyperammonemia by CRRT in a neonate with OTC deficiency.


Management of acute otitis media in the 1990s: the decade of resistant pneumococcus.
Acute otitis media (AOM) has become increasingly difficult to treat in the 1990s, the decade of drug-resistant pneumococcus. Throughout the world, drug-resistant strains of this pathogen are being recovered from 20 to 50% of cases of initial untreated AOM, and from 45 to 90% of refractory AOM. Almost as alarming is that beta-lactamase-producing strains of Haemophilus influenzae are currently being isolated in 40 to 50% of cases of AOM in the US. Clinicians can no longer expect 'Pollyanna-like' high rates of clinical resolution for this disease. It is now imperative that they become aware of the regional prevalence of these drug-resistant bacteria and, just as importantly, their patterns of antibacterial resistance. Although some authors would hold that any antibacterial, or even placebo, should be adequate for most cases of AOM, clinical practice appears to suggest otherwise. Amoxicillin, still the first-line therapeutic choice for initial nonrefractory AOM, will often fail. The real dilemma begins when clinicians search for clinical data to select an antibacterial for therapeutic failures--few data are available. Thus, to give optimal treatment to a child who has failed antibacterial therapy--the true actual indication for all second-line antibacterials--they must instead become familiar with the following in vivo and in vitro data: 1. 'In vivo sensitivity data': otherwise known as bacteriological efficacy, in which repeat tympanocentesis is performed in mid-therapy. This reveals the bacterial 'Achilles heel' or weakness for the individual antibacterial agents. 2. Clinical efficacy data: analysis of rates of clinical resolution after therapy in comparative trials which use a single tympanocentesis initially and a 'gold standard' comparator antibacterial. 3. 'Bug to drug' data: comparison of reported middle ear concentrations for each individual antibacterial agent relative to the respective minimum inhibitory concentrations of isolates, particularly drug-resistant pneumococcus and H. influenzae (if possible, obtained from the paediatric respiratory tract). The selection of an antibacterial agent for AOM in any particular case should not be merely a random process. It involves awareness of the pathogens most likely to be observed: with co-infections; after failure with a particular antibacterial (the bacterial 'Achilles heel' of the drug); and at different points in time, whether initially or after therapeutic failures (e.g. first-line versus fourth-line failure).


Uptake, translocation, and physiological effects of hematite (α-Fe2O3) nanoparticles in barley (Hordeum vulgare L.).
There has been a growing concern with the environmental influences of nanomaterials due to recent developments in nanotechnology. This study investigates the impact and fate of hematite nanoparticles (α-Fe2O3 NPs) (∼14 nm in size) on a crop species, barley (Hordeum vulgare L.). For this purpose, hematite NPs (50, 100, 200, and 400 mg/L) were hydroponically applied to barley at germination and seedling stages (three weeks). Inductively coupled plasma mass spectrophotometry (ICP-MS) along with vibrating sample magnetometer (VSM) techniques were used to track the NPs in plant tissues. The effects of NPs on the root cells were observed by scanning electron microscopy (SEM) and confocal microscopy. Results revealed that α-Fe2O3 NPs significantly reduced the germination rate (from 80% in control to 30% in 400 mg/L), as well as chlorophyll (36-39%) and carotenoid (37%) contents. Moreover, the treatment led to a significant decline in the quantum yield of photosystem II (Fv/Fm). Leaf VSM analysis indicated a change in magnetic signal for NPs-treated samples compared with untreated ones, which is mostly attributed to the iron (Fe) ions incorporated within the leaf tissue. Besides, Fe content in the roots and leaf had gradually increased by the increasing doses of NPs, which was confirming NPs' translocation to the aerial parts. Microscopic observations revealed that α-Fe2O3 NPs altered root cell morphology and led to the injury of cell membranes. This study, in the light of our findings, shows that α-Fe2O3 NPs (∼14 nm in size) are taken up by the roots of the barley plants, and migrate to the plant leaves. Besides, NPs are phytotoxic for barley as they inhibit germination and pigment biosynthesis. This inhibition is probably due to the injury of the cell membranes in the roots. Therefore, the use of hematite NPs in agriculture and thereby their environmental diffusion must be addressed carefully.


Bariatric surgery: a viable treatment option for patients with severe mental illness.
Although bariatric surgery has become a recognized treatment for obesity, its utility among patients with severe psychiatric disorders has not been extensively studied. A few studies have reported similar weight loss outcomes in these patients, but psychiatric status after bariatric surgery has been studied only minimally, and it is unknown if exacerbation of the mental illness affects weight loss. The aim of this study was to shed greater light on the issue of serious mental illness and bariatric surgery. Specifically, do patients with a diagnosis of schizophrenia, bipolar I, and bipolar II have poorer weight loss outcomes postbariatric surgery than the general bariatric surgery population? Also, do patients with these diagnoses experience an exacerbation of psychiatric symptoms after bariatric surgery, and if so, is the exacerbation of these disorders linked to poorer weight loss results? Midwest university medical center. A medical record review of approximately 1500 bariatric patients in a Midwest university medical center was conducted to identify those patients with diagnoses of schizophrenia, bipolar I, and bipolar II. Information was gathered on bariatric surgery outcomes and changes in psychiatric status postsurgery. Eighteen patients were identified as undergoing bariatric surgery and having a diagnosis of schizophrenia, bipolar I, or bipolar II. Weight loss in this group was significant and comparable to expected outcomes of absolute weight lost, changes in body mass index, and percentage excess weight loss for patients in the typical bariatric population. Postsurgery psychiatric status was known on 10 patients. All 10 patients experienced some exacerbation of psychiatric problems yet weight loss outcomes were still as expected. Bariatric surgery is a viable obesity treatment option for patients with schizophrenia, bipolar I, and bipolar II disorders. Symptom exacerbations occurred postsurgery, although it is not clear if these were due to the surgery or would have occurred in the normal course of the illness.


Social support as a determinant of life satisfaction in pregnant women and women after surgical delivery.
The aim of the study was to determine whether social support obtained by women in the third trimester of pregnancy and in the postpartum period differs significantly with respect to the mode of delivery and whether there is a difference in the life satisfaction of the studied women.. The study included 195 women in the third trimester of pregnancy and 182 women from the same group after delivery. The Berlin Social Support Scales (BSSS) and the Satisfaction with Life Scale (SWLS) were used in the study. As early as in the third trimester of pregnancy, women who later underwent Caesarean section received significantly more support of all types than women who gave birth physiologically. In the postpartum period, post-Caesarean women received significantly more support of only instrumental nature. No statistically significant differences were found with respect to life satisfaction of the studied groups of women. The results of the present study demonstrate that Caesarean section does not provide greater life satisfaction. Instrumental support plays a crucial role in meeting the caring needs of post-Caesarean women in the postpartum period. The study reveals which type of support is needed by women and highlights the significant role of fathers during childbirth.


[Survey of the frequency of dental caries in children 6-15-years of age in the greater central region].
A study of the prevalence of dental caries in schoolchildren aged 6 to 15 years living in of the Center of France showed that the disease appeared soon after eruption with a high prevalence in both the deciduous and permanent teeth. The periodontal condition, studied by the plaque, calculus and gingival indices, showed a moderate degree of inflammation.


A systematic review and meta-analysis expounding the relationship between methylene tetrahydrofolate reductase gene polymorphism and the risk of intracerebral hemorrhage among populations.
Background: The relationship between methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphism with the risk of intracerebral hemorrhage (ICH) has remained to be controversial in recent years. This meta-analysis is aimed to confirm the association of these. Methods: Systematically searching the related studies from the PubMed, Embase, Cochrane Library, China national knowledge internet database from 1 January 1990 to 1 June 2022. The odd ratio (ORs) and 95% confidence interval (CIs) of gene-disease correlation in various gene models were calculated by fixed or random effect model of meta-analysis. We included 20 case-control studies in this meta-analysis with a total of 1,989 ICH patients and 4,032 health controls originated from Asian, Caucasian, and African populations. Results: The statistical analysis demonstrated the association of MTHFR C677T gene polymorphism with ICH in allele model [ORT VS. C = 1.20 (95%CI: 1.06-1.36)]; homozygote model [OR TT VS. CC = 1.50 (95%CI: 1.20-1.88)]; dominant model [OR CT+ TT VS. CC = 1.23 (95%CI: 1.03-1.48)] and recessive model [ORTT VS. CT+CC = 1.37 (95%CI: 1.17-1.60)]. Besides, we also found the relationship of MTHFR C677T gene polymorphism with Asian in four comparison model (ORT VS. C = 1.19.95%CI:1.09-1.37, ORTT VS. CC = 1.46.95%CI: 1.15-1.85, OR CT+ TT VS. CC = 1.25.95%CI: 1.01-1.54, ORTT VS. CT+CC = 1.34.95%CI: 1.54-1.17) and Caucasian in four comparison model (ORT VS. C = 1.90.95%CI: 1.22-2.97, ORTT VS. CC = 2.67.95%CI: 1.42-5.00, OR CT+ TT VS. CC = 1.56.95%CI: 1.05-2.32, ORTT VS. CT+CC = 2.25.95%CI: 1.46-4.00). But no statistically significant correlation between A1298C polymorphism and the occurrence of ICH was detected in four studies. Conclusion: MTHFR C677T gene polymorphism increases the risk of ICH in Asian and Caucasian populations but has no impact on the incidence in African communities. More importantly, the risk of ICH increases in TT genotype individuals in comparison to CT and CC genotype individuals in Asian and Caucasian populations.


Analysis of microtubule plus-end-tracking proteins in cilia.
The microtubule (MT) plus-end-tracking proteins (+TIPs) belonging to the end binding (EB) protein family have been studied extensively in the context of cytoplasmic MTs and were shown to play pivotal roles in regulating MT dynamics and in recruiting other +TIPs to MT ends. Early studies in the green alga Chlamydomonas reinhardtii showed that EB1 localizes to the distal flagellum tip and the basal body, and subsequent studies using green fluorescent protein-tagged fusion proteins have demonstrated similar localization of EBs in other ciliated organisms, including mammalian cells as demonstrated here. Functional analysis of EBs in cultured mammalian cells revealed that EB1 and EB3 are required for biogenesis of primary cilia. Although mammalian EB3 localizes to the tip of some cilia and induces cilium elongation, EBs primarily seem to promote ciliogenesis via MT minus-end anchoring at the basal body, in turn facilitating vesicular trafficking to the cilium base. Moreover, mammalian EBs were shown to interact with several proteins implicated in MT minus-end anchoring and/or vesicular trafficking to cilia. Recent work suggests that apart from EBs, additional +TIPs may be present at the distal tip of cilia where they could regulate axoneme assembly, stability, or disassembly.


[Primary care physicians behaviour in inadequate blood pressure control].
To investigate the behaviour of primary care (PC) physicians on inadequate hypertension control. Cross-sectional and multicentric study. PC clinics in the whole of Spain. Patients > or =18 years old who followed pharmacological antihypertensive treatment since at least 3 months before, selected by a consecutive sampling. Blood pressure measured by family doctors. The therapeutic diagram used before and after the visit was registered, and in those cases in which some kind of modification was adopted, the reasons why. 12,754 hypertensive patients were included. The average age was 63.3+/-10.9 years (57.3% women). A 65% lived in urban areas and the 35% in semi-urban o rural areas. The 63.9% (95% confidence interval, 63.1%-64.8%) showed a bad control of hypertension. The majority of the patients followed a therapeutic regimen of monotherapy (56%) being the ACE inhibitors the most prescribed drug (34.8%), followed by the calcium antagonist (21.3%), and angiotensin II antagonists (17.4%). The percentage of patients with inadequate control of the blood pressure, in which the therapeutic behaviour was modified was 18.3% (95% confidence interval, 17.5%-19.1%) (a change of drug in 47%, association in 34.7% and an increase in the dose in 18.3%). The main reasons for which the therapeutic behaviour was modified was because no drug efficacy (63.7%) and the presence of adverse events (5.5%). The price of the therapy originated 1.2% of the modifications. PC physicians behaviour was conservative in uncontrolled hypertension cases. Amongst the doctors who modified their behaviour, by inadequate blood pressure control, the change of drug was the decision most adopted.


5'-,3'-inverted thymidine-modified antisense oligodeoxynucleotide targeting midkine. Its design and application for cancer therapy.
Oligodeoxynucleotides modified at both 5'- and 3'-ends with inverted thymidine (5'-,3'-inverted T) were introduced as new reagents for antisense strategies. These modifications were performed to make the oligodeoxynucleotides resistant to nucleases. The effectiveness of these oligodeoxynucleotides was evaluated in terms of inhibition of synthesis of midkine (MK), a heparin-binding growth factor, and consequent inhibition of growth of CMT-93 mouse rectal carcinoma cells. 5'-,3'-Inverted T antisense MK suppressed synthesis of MK by CMT-93 cells and their growth in culture. Furthermore, 5'-,3'-inverted T oligodeoxynucleotides exhibited less cytotoxicity and better stability than phosphorothioate oligodeoxynucleotides. When 5'-,3'-inverted T antisense MK was mixed with atelocollagen, and injected into CMT-93 tumors pregrown in nude mice, tumor growth was markedly suppressed as compared with tumors injected with sense controls. The suppressive effect of 5'-,3'-inverted T antisense MK on tumor growth was stronger than that of phosphorothioate antisense MK. These findings indicated the usefulness of inverted thymidine-modified antisense oligodeoxynucleotides as a new reagent instead of phosphorothioate-modified oligodeoxynucleotides.


Retracted: Value of Multislice Spiral CT in Differential Diagnosis of Thick-Wall Gallbladder Carcinoma and Chronic Cholecystitis.
[This retracts the article DOI: 10.1155/2022/5459779.].


The involvement of two or more systems and the severity of associated anomalies significantly influence mortality in esophageal atresia.
The aim of this study was to examine the influence of associated anomalies in babies born with esophageal atresia (EA). A retrospective review of the records of 41 consecutive cases of esophageal atresia managed over an 11-year period was undertaken. A higher incidence of associated anomalies was seen in those babies with lower birth weights. Although all five (100%) babies with EA who weighed less than 1,800 g had associated anomalies, those who weighed 1,800 to 2,500 g and more than 2,500 g were associated with 67% (10 of 15) and 43% (9 of 21) anomalies, respectively. The most common system in which anomalies occurred was the cardiovascular system (37%) followed by gastrointestinal (24%), musculoskeletal (17%), genitourinary (7%), chromosomal (5%), and others (12%). All 17 (41%) babies with no associated anomalies survived. Four of the 10 babies who had two or more systems involvement died, whereas only one of 31 babies with less than two systems involvement died; the difference between these two groups was highly significant (Fisher's Exact test, P = .009). The overall mortality rate was 12%. Three of the deaths were associated with severe anomalies that were incompatible with life such as bilateral renal agenesis, trisomy 18, and complex cardiac anomalies. The association of two or more system anomalies and the severity of associated anomalies influence mortality in esophageal atresia.


Delta check for blood groups: A step ahead in blood safety.
Blood grouping is the single most important test performed by each and every transfusion service. A blood group error has a potential for causing severe life-threatening complications. A number of process strategies have been adopted at various institutions to prevent the occurrence of errors at the time of phlebotomy, pretransfusion testing, and blood administration. A delta check is one such quality control tool that involves the comparison of laboratory test results with results obtained on previous samples from the same patient. We retrieved the records of all transfusion-related incidents reported in our institute, between January 2008 and December 2014. Errors identified as "Failed Delta checks" and their root cause analyses (RCA) were reviewed. A total of 17,034 errors related to blood transfusion were reported. Of these, 38 were blood grouping errors. Seventeen blood group errors were identified due to failed delta checks, where the results of two individually drawn grouping samples yielded different blood group results. The RCA revealed that all of these errors occurred in the preanalytical phase of testing. Mislabeling resulting in wrong blood in tube was the most commonly identified cause, accounting for 11 of these errors, while problems with correct patient identification accounted for 5 failed delta checks. Delta checks proved to be an effective tool for detecting blood group errors and prevention of accidental mismatched blood transfusions. Preanalytical errors in patient identification or sample labeling were the most frequent.


Phosphine-Catalyzed Sequential [4 + 3] Domino Annulation/Allylic Alkylation Reaction of MBH Carbonates: Efficient Construction of Seven-Membered Heterocycles.
Phosphine-catalyzed intermolecular sequential [4 + 3] domino annulation/allylic alkylation of MBH carbonates and N-tosyl azadienes is reported. A series of functionalized benzofuran-fused seven-membered nitrogen-heterocyclic compounds with one quaternary center were obtained in good to excellent yields. In this sequential reaction, three new bonds were formed in one pot, and the MBH carbonates serve as 1,2,3-C3 synthon and C1 synthon at the same time.


Lack of effect of olanzapine on the pharmacokinetics of a single aminophylline dose in healthy men.
To test whether olanzapine, an atypical antipsychotic, is an inhibitor of cytochrome P450 (CYP) 1A2 activity, we conducted a drug interaction study with theophylline, a known CYP1A2 substrate. Two-way, randomized, crossover study. Clinical research laboratory. Nineteen healthy males (16 smokers, 3 nonsmokers). Because the a priori expectation was no effect of olanzapine on theophylline pharmacokinetics, a parallel study using cimetidine was included as a positive control. In group 1, 12 healthy subjects received a 30-minute intravenous infusion of aminophylline 350 mg after 9 consecutive days of either olanzapine or placebo. In group 2, seven healthy subjects received a similar aminophylline infusion after 9 consecutive days of either cimetidine or placebo. Concentrations of theophylline and its metabolites in serum and urine were measured for 24 and 72 hours, respectively. Plasma concentrations of olanzapine and its metabolites were measured for 24 hours after the next to last dose and 168 hours after the last olanzapine dose. Olanzapine did not affect theophylline pharmacokinetics. However, cimetidine significantly decreased theophylline clearance and the corresponding formation of its metabolites. Urinary excretion of theophylline and its metabolites was unaffected by olanzapine but was reduced significantly by cimetidine. Steady-state concentrations of olanzapine (15.3 ng/ml), 10-N-glucuronide (4.9 ng/ml), and 4'-N-desmethyl olanzapine (2.5 ng/ml) were observed after olanzapine 10 mg once/day and were unaffected by coadministration of theophylline. As predicted by in vitro studies, steady-state concentrations of olanzapine and its metabolites did not affect theophylline pharmacokinetics and should not affect the pharmacokinetics of other agents metabolized by the CYP1A2 isozyme.


Overview of cerebrospinal fluid cytology.
Cerebrospinal fluid (CSF) cytology, i.e., the cytologic evaluation of its cellular composition, forms an integral part of the neurologist's armamentarium. Total and differential cell counts provide important first information across a spectrum of pathologic conditions involving the central nervous system and its coverings. CSF samples require immediate processing, ideally within 1 hour from collection. Upon centrifugation cytology is commonly assessed on May-Grunwald-Giemsa stains. Several additional stains are available for the identification of infectious agents such as bacteria or fungi, or the further specification of neoplastic cells by immunocytochemistry. The evaluation warrants familiarity with cytologic characteristics of cells across normal and diseased states. In normal CSF, lymphocytes and monocytes are encountered. A predominance of neutrophil granulocytes suggests bacterial meningitis and prompts search for intracellular bacteria. In contrast, in viral and chronic infections lymphocytes and monocytes prevail. Upon activation lymphocytes typically enlarge and eventually differentiate into plasma cells. Similarly, monocytes differentiate into macrophages that clear cellular debris. Macrophages that contain fragments of erythrocytes or hemoglobin degradation products are referred to as erythro- or siderophages, both of which indicate prior subarachnoid hemorrhage. Likewise, the detection of tumor cells is specific for neoplastic meningitis, although false-negative CSF cytologies are frequent. In summary, detailed morphologic workup of CSF samples provides valuable diagnostic information and is mandated in all cases with elevated cell count, computed tomography-negative suspected subarachnoid hemorrhage, and neoplastic meningitis. In all cases it needs to be interpreted in the clinical context and complements other clinical and laboratory findings.


Apolipoprotein E ε4 triggers neurotoxicity via cholesterol accumulation, acetylcholine dyshomeostasis, and PKCε mislocalization in cholinergic neuronal cells.
The Apolipoprotein E (ApoE) has been known to regulate cholesterol and β-amyloid (Aβ) production, redistribution, and elimination, in the central nervous system (CNS). The ApoE ε4 polymorphic variant leads to impaired brain cholesterol homeostasis and amyloidogenic pathway, thus representing the major risk factor for Alzheimer's Disease (AD). Currently, less is known about the molecular mechanisms connecting ApoE ε4-related cholesterol metabolism and cholinergic system degeneration, one of the main AD pathological features. Herein, in vitro cholinergic neuron models were developed in order to study ApoE neuronal expression and investigate the possible interplay between cholesterol metabolism and cholinergic pathway impairment prompted by ε4 isoform. Particularly, alterations specifically occurring in ApoE ε4-carrying neurons (i.e. increased intracellular ApoE, amyloid precursor protein (APP) and Aβ levels, elevated apoptosis, and reduced cell survival) were recapitulated. ApoE ε4 expression was found to increase intracellular cholesterol accumulation, by regulating the related gene expression, while reducing cholesterol precursor acetyl-CoA, which in turn fuels the acetylcholine (ACh) synthesis route. In parallel, although the ACh intracellular signalling was activated, as demonstrated by the boosted extracellular ACh as well as increased IP3 and Ca2+, the PKCε activation via membrane translocation was surprisingly suppressed, probably explained by the cholesterol overload in ApoE ε4 neuron-like cells. Consequently, the PKC-dependent anti-apoptotic and neuroprotective roles results impaired, reliably adding to other causes of cell death prompted by ApoE ε4. Overall, the obtained data open the way to further critical considerations of ApoE ε4-dependent cholesterol metabolism dysregulation in the alteration of cholinergic pathway, neurotoxicity, and neuronal death.


[Reaction in bone and cartilage to Judet metal prosthesis over 20 years (author's transl)].
A case in which a vitallium head-prosthesis was implanted 20 years before. Changes in the neck of femur: Vitallium proved even after 20 years very passive. Minor metallosis could be seen only microscopically, no inflammatory or foreign-body reaction, no atrophy but sclerosis of cancellous bone, which is considered to be due to adaptation to changed weightbearing. Losening of the implant caused a kind of "pseudarthrosis" on the surface of the bed, definite secondary changes, in parts osteoarthrotic. The causes of "pseudarthrosis" are discussed.


External validation of FXYD3 and KRT20 as predictive biomarkers for the presence of micrometastasis in muscle invasive bladder cancer lymph nodes.
Recent studies have proposed that FXYD3 and KRT20 mRNA quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in paraffin could be biomarkers to detect lymph nodes with micrometastases that avoid detection by conventional analysis with hematoxylin-eosin (HE). A validation study was conducted on the lymph nodes of patients who underwent radical cystectomy. To classify the adenopathic state of a sample of patients who underwent cystectomy, based on the lymph node expression of FXYD3 and KRT20. The secondary objective was to assess whether there is a differential oncologic evolution for the patients, depending on the lymph node expression of these proteins. The study included lymph nodes from 64 patients who underwent cystectomy for infiltrating bladder tumor: The model was developed using metastatic lymph nodes from 15 patients and lymph nodes from 4 patients with no known tumor. Genetic expression was measured using real-time qRT-PCR. We calculated (using qRT-PCR) the median expression of FXYD3 and KRT20 mRNA in the lymph node tissue. We then analyzed the receiver operating characteristic (ROC) curves, according to the function y=0.1400+0.250FXYD3-2.532. The cutoff was established using an ROC curve. The formula was applied to the remaining lymph node tissue, based on the previously established cutoff. The sample was classified into 4 subgroups: HE- qRT-PCR-, HE- qRT-PCR+, HE+ qRT-PCR+ y HE+, qRT-PCR-. A descriptive, comparative analysis was performed, as well as a metastatic progression-free survival analysis, calculating the Kaplan and Meyer curves for the 3 established subgroups. The test results were considered statistically significant at P<.05. Using qRT-PCR, we verified that there were differences in the median expression of FXYD3 (P=.05) and KRT20 (P=.009) between the lymph node tissues of patients with benign prostate hyperplasia and those of patients with lymph node metastasis. A cutoff was assigned to 0.377. The sample was classified as follows: 37.5% of the patients were pN0 by HE and pN0 by qRT-PCR (-HE -qRT-PCR), 39.1% were pN0 by HE but metastatic by qRT-PCR (-HE +qRT-PCR), and 15 patients (23.4%) were metastatic by both techniques (+HE +qRT-PCR). The Kaplan and Meyer curves showed poorer metastatic progression-free survival for the patients who were +HE and +qRT-PCR than for the other subgroups, with no significant differences between -HE +qRT-PCR and -HE -qRT-PCR. According to our results, 39.1% of the patients with infiltrating vesical tumors overexpressed the FXYD3 and KRT20 biomarkers and were N0 by HE. We observed no differential clinical behavior among the patients who underwent cystectomy according to their expression of FXYD3 and KRT20 when they were N0 by HE.


Improved Outcome of Alternative Donor Transplantations in Patients with Myelofibrosis: From Unrelated to Haploidentical Family Donors.
This is a retrospective analysis of 95 patients with myelofibrosis who were allografted between 2001 and 2014. The aims of the study were to assess whether the outcome of alternative donor grafts has improved with time and how this compares with the outcome of identical sibling grafts. Patients were studied in 2 time intervals: 2000 to 2010 (n = 58) and 2011 to 2014 (n = 37). The Dynamic International Prognostic Scoring System score was comparable in the 2 time periods, but differences in the most recent group included older age (58 versus 53 years, P = .004), more family haploidentical donors (54% versus 5%, P < .0001), and the introduction of the thiotepa-fludarabine-busulfan conditioning regimen (70% of patients versus 2%, P < .0001). Acute and chronic graft-versus-host disease were comparable in the 2 time periods. The 3-year transplantation-related mortality (TRM) in the 2011 to 2014 period versus the 2000 to 2010 period is 16% versus 32% (P = .10), the relapse rate 16% versus 40% (P = .06), and actuarial survival 70% versus 39% (P = .08). Improved survival was most pronounced in alternative donor grafts (69% versus 21%, P = .02), compared with matched sibling grafts (72% versus 45%, P = .40). In conclusion, the outcome of allografts in patients with myelofibrosis has improved in recent years because of a reduction of both TRM and relapse. Improvement is most significant in alternative donor transplantations, with modifications in donor type and conditioning regimen.


Lung anomaly detection from respiratory sound database (sound signals).
Chest or upper body auscultation has long been considered a useful part of the physical examination going back to the time of Hippocrates. However, it did not become a prevalent practice until the invention of the stethoscope by Rene Laennec in 1816, which made the practice suitable and hygienic. Pulmonary disease is a kind of sickness that affects the lungs and various parts of the respiratory system. Lung diseases are the third largest cause of death in the world. According to the World Health Organization (WHO), the five major respiratory diseases, namely chronic obstructive pulmonary disease (COPD), tuberculosis, acute lower respiratory tract infection (LRTI), asthma, and lung cancer, cause the death of more than 3 million people each year worldwide. Respiratory sounds disclose significant information regarding the lungs of patients. Numerous methods are developed for analyzing the lung sounds. However, clinical approaches require qualified pulmonologists to diagnose such kind of signals appropriately and are also time consuming. Hence, an efficient Fractional Water Cycle Swarm Optimizer-based Deep Residual Network (Fr-WCSO-based DRN) is developed in this research for detecting the pulmonary abnormalities using respiratory sounds signals. The proposed Fr-WCSO is newly designed by the incorporation of Fractional Calculus (FC) and Water Cycle Swarm Optimizer WCSO. Meanwhile, WCSO is the combination of Water Cycle Algorithm (WCA) with Competitive Swarm Optimizer (CSO). The respiratory input sound signals are pre-processed and the important features needed for the further processing are effectively extracted. With the extracted features, data augmentation is carried out for minimizing the over fitting issues for improving the overall detection performance. Once data augmentation is done, feature selection is performed using proposed Fr-WCSO algorithm. Finally, pulmonary abnormality detection is performed using DRN where the training procedure of DRN is performed using the developed Fr-WCSO algorithm. The developed method achieved superior performance by considering the evaluation measures, namely True Positive Rate (TPR), True Negative Rate (TNR) and testing accuracy with the values of 0.963(96.3%), 0.932,(93.2%) and 0.948(94.8%), respectively.


NMDA receptor subunit NR1-immunoreactivity in the rat pons and brainstem and colocalization with Fos induced by nasal stimulation.
In the present study, we examined the distribution of neurons in the parabrachial nucleus (PB), the Kölliker-Fuse nucleus (KF), the spinal trigeminal nucleus caudalis (Sp5C), the nucleus of the solitary tract (NTS) and the ventrolateral medulla (VLM), which are activated by evoking the nasotrigeminal reflex and which exhibit immunoreactivity for the N-methyl-D-aspartate (NMDA) receptor subunit NR1. By stimulating the nasal mucosa with saline, we induced the expression of the immediate early gene c-fos and combined the immunocytochemical detection of the Fos protein with the detection of the NR1 subunit. Cell counts revealed that nasal stimulation, compared to anesthesia controls, resulted in highly significant increases (p < or = 0.001) of Fos-immunoreactive (-ir) neurons in the midlevel KF, the external lateral PB, and the Sp5C. In the central lateral PB, the rostral ventrolateral medulla including the Bötzinger/pre-Bötzinger complex, and in the ventrolateral and commissural NTS the increases were only moderately significant (p < or = 0.05). With respect to the numbers of NR1-/Fos-ir double-labeled neurons, significant increases were only observed in a subset of these pontomedullary nuclei. Increases were highly significant in the Sp5C (p < or = 0.001) and the midlevel KF (p < or = 0.01) and moderately significant (p < or = 0.05) in the external lateral PB, Bötzinger/pre-Bötzinger complex, and ventrolateral NTS. The present study revealed that nasotrigeminally activated neurons in mandatory and potential relay sites of the nasotrigeminal reflex circuit express the NR1 subunit. This finding strongly suggests that NMDA-type glutamate receptors are involved in the mediation of the nasotrigeminally evoked cardiovascular and respiratory responses.


Intraarticular nodular fasciitis of the hip.
Intraarticular nodular fasciitis is a rare lesion that has only recently been recognised. We present a case of intraarticular nodular fasciitis of the hip joint in a 25-year-old woman, who presented with a 9-month-history of right groin pain and a decreased range of right hip motion. A polypoid mass, composed of five nodules attached to the synovial membrane of the distal peripheral compartment of the hip was removed arthroscopically, together with two detached nodules. Histopathological examination revealed a myofibroblastic proliferation typical of nodular fasciitis. Complete resolution of symptoms and restoration of function was achieved, without recurrence 2 years after removal of the lesion. To the best of our knowledge, this is the first case of intraarticular nodular fasciitis of the hip, presenting a new indication for arthroscopic treatment.


Motor activity and visually induced postural reactions during two-g and zero-g phases of parabolic flight.
Maintenance of an upright posture was measured in human subjects during increased and decreased gravitoinertial force phases of parabolic flight. Upright posture was maintained by tonic activity of the ankle joint extensor muscle (soleus) during the one-g or two-g phases. During the zero-g phase the same posture was maintained primarily by activity of the flexor muscle (tibialis). Downward and upward optokinetic stimulation induced strong postural reactions directed forwards and backwards, respectively. These reactions were accompanied by changes of motor activity of the flexor muscle. This suggests a rapid redistribution of motor programs between extensor and flexor muscles with an increase in visual input influence, and confirms results obtained during space flight.


[Surgical treatment of tumors of the spine with compression of the spinal cord].
The long-term results of surgical treatment of various tumors of the vertebral column in 53 patients are analysed. Treatment of malignant tumors, both primary and solitary metastatic, should be combined. Porous allografts filled with a chemical agent are suggested for use. Radio- and chemotherapy can be applied both before and after the operation. Primary decompression and stabilization, and if necessary--radiotherapy, are recommended in benign spinal tumors.


Effects of newly-developed benzodiazepine ligands on noise-induced mitochondrial damage in the rat.
In this study we measured the ability of three newly-synthesized N-arylalkylindol-3-ylglyoxylylamide derivatives, which have recently been characterized as partial agonists at central benzodiazepine binding sites, to prevent the rat cardiac mitochondrial alterations resulting from acute loud noise exposure. In particular, we evaluated the effects of these new compounds on the ultrastructural damage induced by noise stress on the right atrium and ventricle after 6 and 12 hr of loud noise exposure. In parallel experiments, we measured the affinity of these compounds for peripheral benzodiazepine binding sites. Following a single injection of the test products, we observed a cardioprotective effect which was more marked after 6 hr compared with 12 hr of noise exposure. Confirming our recent data showing that full agonists at benzodiazepine receptors produce cardioprotection, we demonstrate in this study that partial agonists, like indolylglyoxylylamides, can also produce a cardioprotective effect. Based on their greater affinity in binding studies, the protective activity seems to be related more to their action at central than at peripheral benzodiazepine receptors.


The benefits and perils of system integration.
The current health care environment is complex, with no single systems solution dominating the marketplace. A new approach utilizes Networked Systems Integration to link disparate systems together. This paper discusses the Systems Integration approach and suggests that it encourages user commitment, provides greater modularity, is cost effective, and supports solutions that offer greater functionality. However, it is noted that this approach is not without problems that can dramatically effect the realization of benefits.


Water, sanitation, and hygiene vulnerability in child stunting in developing countries: a systematic review with meta-analysis.
This study aimed to perform a systematic review and meta-analysis to assess the scientific evidence of the relationship between vulnerability to access to safe drinking water, sanitation, and hygiene (WASH) practices on stunting in children aged <5 years in developing countries. This is a systematic review and meta-analysis article to assess the relationship between under-five stunting and WASH vulnerability in developing countries. The systematic review with meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol methodology. The following databases were used: LILACS, MEDLINE (via PubMed), SciELO, Web of Science, ScienceDirect, SCOPUS, and Embase. All original studies identified that related WASH vulnerability to stunting in children aged <5 years in developing countries was included. Three authors performed independently the selection and extraction of data from the articles. The statistical software STATA version 11 was used. Cochran's Q test and Chi-square test (I2) with 95% significance were used to assess the heterogeneity of the studies. The search resulted in the initial identification of 2047 articles; after reading the abstracts, followed by the full articles, 14 articles were included in the systematic review and eight articles were included in the meta-analysis. The studies selected for the systematic review were published between the years 1992 and 2021 and conducted in eight countries, namely, Ethiopia, India, Indonesia, Bangladesh, Tanzania, Peru, China, and Lesotho. The studies assessed vulnerability to access to WASH on the growth of children aged <5 years. There was a significant difference when relating WASH vulnerability to children's height. The meta-analysis of this study showed that the impact of WASH on child stunting is significant when it comes to lack of sanitation in 72% of the studies. The study found that WASH vulnerability contributes to stunting in children aged <5 years in developing countries. Based on our findings, we recommend incorporating WASH strategies, especially sanitation, into the formulation of interventions integrating with health promotion policies for healthy early childhood development.


Ecdysteroid-responsive genes, RXR and E75, in the tropical land crab, Gecarcinus lateralis: differential tissue expression of multiple RXR isoforms generated at three alternative splicing sites in the hinge and ligand-binding domains.
In order to study the potential role of the steroid molting hormone (20-hydroxyecdysone) in regulating molt-induced claw muscle atrophy, full-length cDNAs encoding retinoid-X receptor (Gl-RXR) and E75 early ecdysone inducible gene (Gl-E75) were obtained from land crab (Gecarcinus lateralis) skeletal muscle mRNA using RT-PCR and 3' and 5' RACE. Gl-E75A (3528bp), which encoded a protein of 828 amino acids, had highest sequence identity to Me-E75A from a shrimp (Metapenaeus ensis). It was expressed in skeletal muscle and gonads. The deduced amino acid sequence of Gl-RXR was highly similar to that of the fiddler crab RXR (Up-RXR) and insect ultraspiracle (USP). Nine variant sequences occurred in Gl-RXR mRNAs at three alternative splicing sites, one in the "T box" in the linker D domain and two in the ligand-binding domain (LBD). The three T-box variants, termed T(+8), T(+7), and T(+12), contained insertions of 8, 7, or 12 amino acids, respectively. Four variants were generated at the first site in the LBD. Two of the LBD site 1 variants differed in the presence (+33) or absence (-33) of a 33-amino acid sequence; the other two were LBD truncations with or without the 33 amino acid sequence (+33DeltaE/F and -33DeltaE/F, respectively). Two variants differing in the presence (+35) or absence (-35) of a 35-amino acid sequence were generated at the second site in the LBD. The Gl-RXRa isoform (1516 bp) with the longest open reading frame (+12/+33/+35) encoded a protein of 436 amino acids. Thoracic muscle expressed only isoforms with the T(+12) sequence. In contrast, claw muscle expressed isoforms with T(+7) or T(+12) and fewer isoforms with T(+8). Ovary and testis expressed a greater number of RXR isoforms than skeletal muscle. All tissues expressed full-length and truncated RXR isoforms. These data suggest that differences in response of claw and thoracic muscles to elevated ecdysteroid are due in part to differences in the expression of RXR isoforms.


Translocation (X;9)(p11;q34) in a girl with incontinentia pigmenti (IP): implications for the regional assignment of the IP locus to Xp11?
A t(X;9)(p11;q34) is reported in a girl with incontinentia pigmenti (IP). The X breakpoint is at p11.21. Although no similar case has been reported, this breakpoint may be significant insofar IP is considered an X-linked dominant mutation and could be of help in a specific X DNA probes study.


The conceptualization of physical restraint as a nursing-sensitive adverse outcome in acute care psychiatric treatment settings.
The occurrence of physical restraint episodes in psychiatric settings is a major public health issue because the therapeutic utility of this form of behavior control has not been substantiated empirically. The purpose of this article was to examine the extant literature to determine if evidence supports the conceptualization of a physical restraint episode as an adverse client outcome that is sensitive to the organization of nursing care in psychiatric settings. An adapted version of the Quality Health Outcomes Model (Mitchell, P. H., Ferketich, S., & Jennings, B. M. (1998). Quality Health Outcomes Model. Image Journal of Nursing Scholarship, 30, 43-46) was used as the conceptual model to guide this inquiry. The databases Cumulative Index to Nursing and Allied Health Literature, Health and Psychosocial Instruments, HealthSTAR/Ovid and Healthstar, Medline, and psychINFO were searched from 1990 to 2005. There are 101 sources in this review. Evidence strongly suggests that a physical restraint episode is an adverse outcome that is sensitive to the organization of nursing care. A systematic exploration of the specific structures and processes of the organization that affect adverse outcomes, such as physical restraint episodes, is lacking in the United States.


Low-dose chemotherapy in combination with COX-2 inhibitors and PPAR-gamma agonists in recurrent high-grade gliomas - a phase II study.
Combined treatment approaches targeting tumor as well as other cells contributing to tumor progression may control chemorefractory malignancies. A phase II trial was initiated to analyze the activity of continuously administered pioglitazone and rofecoxib combined with low-dose chemotherapy (capecitabine or temozolomide) in patients with high-grade gliomas (glioblastoma or anaplastic glioma). Fourteen patients were evaluable for response and toxicity. Major side effects were palmoplantar erythema, edema and motor neuropathy grade 3. Disease stabilizations lasting longer than 3 months were noted in 4 of 14 patients (29%). Clinical responses did not correspond to immunohistochemical staining for cyclooxygenase 2, peroxisome proliferator-activated receptor-gamma and CD31. The study demonstrates that this novel regimen is moderately active and well tolerated in patients with high-grade gliomas. As a comparably small proportion of patients responded, the regimen might only be suitable for a subset of highly selected patients.


Biosynthesized silver nanoparticles using Bacillus amyloliquefaciens; Application for cytotoxicity effect on A549 cell line and photocatalytic degradation of p-nitrophenol.
The present study reports the biosynthesis of silver nanoparticles (AgNPs) using Bacillus amyloliquefaciens MSR5. The cellfree supernatant of B. amyloliquefaciens acted as a stabilizing agent for the synthesis of AgNPs. The synthesized AgNPs were characterized using UV-vis spectrophotometer, PXRD, FTIR, SEM-EDX, DLS, and TEM. TEM image showed the spherical shape of the biosynthesized AgNPs and it was found to be 20-40 nm in range. In this study, the AgNPs were prepared by ultrasonic irradiation. The stability of the AgNPs was found to be -33.4 mV using zeta potential. The catalytic 4-nitrophenol (4-NP) degradation by AgNPs was examined under solar irradiation and furthermore, the effects of several degradation parameters were studied. The biosynthesized AgNPs exhibited a strong chemocatalytic action with a comprehensive degradation (98%) of 4-NP to 4-aminophenol (4-AP) using NaBH4 within 15 min. In addition, MTT assay was performed to evaluate the cytotoxicity of the biosynthesized AgNPs (10 - 200 μg). The results have shown that the AgNPs exhibited significant activity on A549 cells, which was dosedependent. The study elucidates the AgNPs synthesized using cellfree culture supernatant can be used for the elimination of hazardous pollutants from wastewater.


Computer-Assisted and Hip Arthroscopy for Avascular Necrosis of the Femoral Head With Femoroacetabular Impingement.
Avascular necrosis of the femoral head with femoroacetabular impingement is a disabling disease. Without early treatment and intervention, its further development will even lead to hip osteoarthritis and hip dysfunction. This technical note aims to introduce a computer-assisted precise core decompression of the femoral head, followed by injection of platelet-rich plasma and bone marrow aspirate concentrate. Then, the autologous ipsilateral iliac bone is transplanted to the core decompression area. Thereafter, under hip arthroscopy, the injured glenoid lip of the hip joint is repaired, and the cam deformity of the femoral head/neck junction is polished and formed. The advantages of this technique include accurately locating the core decompression area, combined with autologous cells and bone transplantation, being able to delay the process of avascular necrosis of the femoral head, and evaluating articular cartilage injury, subchondral collapse, and guidance during reaming and curettage.


Impact of exercise timing on perceived appetite and food reward in early and late chronotypes: An exploratory study in a male Saudi sample.
There is very limited evidence on the influence of diurnal exercise timing on appetite control, and none on food reward or how an individual's chronotype could moderate such effects. We examined the impact of acute exercise timing on perceived appetite and food reward in young Saudi adults with early or late chronotypes. Forty-five young adults (23 ± 4 years; BMI = 25.1 ± 4.0 kg/m2) completed the Morningness-Eveningness Questionnaire (MEQ) and were divided into early (score = 59 ± 5) or late (score = 41 ± 6) chronotypes. Participants attended the laboratory after ≥4 h fast on two occasions for an AM (8:00-10:00) and PM (17:00-19:00) 30-min moderate-intensity cycling bout in a randomized counterbalanced order. Appetite ratings and food reward (Arab Leeds Food Preference Questionnaire) were measured before and after exercise. An acute exercise-induced decrease in hunger was found, which appeared to be dependent upon diurnal timing and chronotype, with hunger being more suppressed after AM exercise in the early chronotypes and after PM exercise in the late chronotypes. There was greater wanting for low-fat sweet foods after AM exercise relative to PM exercise, whereas there was greater wanting for high-fat sweet food and sweet relative to savoury food after PM exercise compared to AM exercise. These preliminary findings suggest that diurnal timing of exercise impacts food preferences, and that chronotype may influence the appetite response to an exercise bout at different times of day.


Modeling of the respiratory system of the long-necked Triassic reptile Tanystropheus (Archosauromorpha).
All known species of the Triassic archosauromorph genus Tanystropheus are known to have had the longest neck in proportion to their torso. This feature is related to a series of ventilatory challenges since an increase in neck length also increases airway length and, therefore, the volume of stagnant air that does not reach the lungs, the dead space volume. Based on this challenge, the objective of the present study was to model the type of respiratory system of Tanystropheus able to meet its metabolic demands during the early Triassic period. The modeling was based on allometric relations for morphological and physiological ventilatory and metabolic variables, and to do so, the mean body mass of Tanystropheus was estimated based on three different methods. In addition, the tracheal airflow was also estimated based on the proportions of Tanystropheus elongated neck, the results of allometric modeling, and fundamental equations of fluid mechanics. The estimation of the body mass indicated that an animal of 3.6 m would possess a body mass of 50.6 ± 21.6 kg. Allometric modeling suggested that the respiratory system best suited to Tanystropheus' oxygen demands, especially during activity, would be a generic reptilian-like respiratory system composed of multicameral lungs. The best respiratory pattern to maintain adequate tracheal flow rates and effective pulmonary ventilation would be one ventilating the relatively narrower trachea at lower frequencies to deal with tracheal dead space volume.


How to treat hepatic pulmonary fusion: case report with review of literature.
Introduction: Hepatic pulmonary fusion (HPF) occurring with right diaphragmatic hernia is rare. Some sporadic reports exist in the literature. It may range from just fibrovascular communication to complete parenchymal fusion which may be complex to divide.Patients and methods: We report a case of a 1-day old newborn male presented with respiratory distress relevant to a right diaphragmatic hernia.Results: The patient was operated after initial stabilization. During surgery, a 10-cm wide posterolateral defect was found. The herniated liver was only partially reducible because of HPF. This rare condition was treated by the division of the fusion and diaphragm repair using a vicryl patch.Conclusion: Through our case and a review of the literature, we will discuss the different alternatives in the treatment of HPF.


An open clinical trial of cognitive-behaviour therapy in children and adolescents with obsessive-compulsive disorder administered in regular outpatient clinics.
The aim of the present study was to examine the effectiveness of manual-guided cognitive-behaviour therapy (CBT) for childhood obsessive-compulsive disorder (OCD) administered within three regular, i.e., non-academic, Norwegian outpatient child psychiatric clinics. A total of 28 youngsters, aged 8-17 with primary OCD entered the study. Assessment at intake included Norwegian versions of the K-SADS-PL, Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and a measure of OCD-specific functional impairment (Child OCD Impact Scale (COIS)). Therapy consisted of 12 manual-guided sessions with combined individual and family CBT-based interventions and was conducted by psychologists and physicians under training and supervision. Outcome was assessed after treatment and at 3- and 6-month follow-ups by means of the CY-BOCS, the Clinical Global Impression (CGI) and the CGI-Improvement scales, and the COIS. Twenty-four youngsters (86%) completed treatment and were available for the follow-up assessments. Significant improvements were found on all outcome measures after treatment, including a mean symptom reduction on the CY-BOCS of 60.6%, increasing to 68.8% at the 6-month follow-up. Estimates of within-group effect sizes showed strong effects of treatment. The results of the present study suggest that manual-guided CBT for childhood OCD can be successfully implemented in non-academic community child psychiatric settings with outcomes in accordance with previous findings from highly specialised university clinics.


The exocyst complex.
The exocyst is a multisubunit protein complex that was first identified and characterized in budding yeast. Later studies have demonstrated its conservation in eukaryotes, from plants to mammals. This complex mediates the tethering of secretory vesicles to the plasma membrane prior to fusion mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The exocyst has been implicated in a variety of cellular processes, such as exocytosis, cell growth, cytokinesis, cell migration, primary ciliogenesis and tumorigenesis. Recent years have seen major progress in our understanding of this complex. In this Primer, we focus on some of the basic information about the exocyst complex, including its structure, assembly, molecular interactions, function in vesicle tethering and membrane fusion, and involvement in many physiological processes.


Maintenance of cellular respiration indicates drug resistance in acute myeloid leukemia.
Primary resistance to induction therapy is an unsolved clinical problem in acute myeloid leukemia (AML). Here we investigated drug resistance in AML at the level of cellular metabolism in order to identify early predictors of therapeutic response. Using extracellular flux analysis, we compared metabolic drug responses in AML cell lines sensitive or resistant to cytarabine or sorafenib after 24h of drug treatment to a small cell lung cancer (SCLC) cell line exposed to etoposide. Only drug-resistant AML cells maintained oxidative metabolism upon drug exposure while SCLC cells displayed an overall metabolic shift towards glycolysis, i.e. a Warburg effect to escape drug toxicity. Moreover, primary AML blasts displayed very low glycolytic activity, while oxygen consumption was readily detectable, indicating an essential role of oxidative pathways in the bioenergetics of AML blasts. In line with these observations, analysis of the mitochondrial membrane potential using tetramethylrhodamine ethyl ester staining and flow cytometry allowed for clear discrimination between drug sensitive and resistant AML cell line clones and primary blasts after 24h of treatment with cytarabine or sorafenib. Our data reveal a distinct metabolic phenotype of resistant AML cells and suggest that disrupting oxidative metabolism rather than glycolysis may enhance the cytotoxic effects of chemotherapy in AML.


Is local intra-arterial fibrinolysis contraindicated in elderly patients with cerebral artery occlusion?
Local intra-arterial fibrinolysis (LIF) is an effective treatment for selected patients in acute thromboembolic occlusion of the middle cerebral artery, vertebrobasilar system or ophthalmic artery. However, the risk/benefit ratio of thrombolysis in patient subgroups requires classification. Advanced age has been regarded as a prognostic factor for poor clinical outcome. We report our experience with LIF in seven patients with a mean age of 79 years (range 76-83 years) who represented thromboembolic occlusion of the basilar, middle cerebral or pericallosal arteries. We discuss why advanced age need not contraindicate LIF.


Detection of nitric oxide from pig trachea by a fluorescence method.
A nitronyl nitroxide radical covalently linked to an organic fluorophore, pyrene, was used to detect nitric oxide (NO) from freshly excited tissues. This approach is based on the phenomenon of the intramolecular fluorescence quenching of the fluorophore fragment by the nitroxide. The pyrene-nitronyl (PN) reacts with NO to yield a pyrene-imino nitroxide radical (PI) and NO(2). Conversion of PN to PI is accompanied by changes in the electron paramagnetic resonance (EPR) spectrum from a five-line pattern (two equivalent N nuclei) into a seven-line pattern (two nonequivalent N nuclei). The transformation of the EPR signal is accompanied by an increase in the fluorescence intensity since the imino nitroxide radical is a weaker quencher than the nitronyl one. The results indicate that the fluorescence measurements enable detection of nanomolar concentrations of NO compared to a sensitivity threshold of only several micromolar for the EPR technique. The method was applied to the determination of NO and S-nitroso compounds in tissue from pig trachea epithelia. The measured basal flux of S-nitroso compounds obtained from the tissues was about 1.2 nmol/g x min, and NO-synthase stimulated by extracellular adenosine 5'-triphosphate produced NO flux of 0.9 nmol/g x min.


A "light" touch on PI3K to interrogate cancer drug resistance.
In this issue of Cell Chemical Biology, Ueda et al. (2022) developed PPAP2 as an improved optogenetic tool to photo-induce PI3K signaling hyperactivation in cancer cells. They demonstrated that enhanced translation of tumor necrosis factor alpha-induced protein 8 (TNFAIP8) might explain PI3K hyperactivation-associated resistance toward DNA damaging anti-cancer alkylating agents.


Queuosine modification in tRNA and expression of the nitrate reductase in Escherichia coli.
In eubacteria the modified nucleoside queuosine is present in tRNAAsn, tRNAAsp, tRNAHis and tRNATyr. A precursor of queuine, pre-queuine, is synthesized from GTP, inserted into the first position of the anticodon of the corresponding tRNAs by a specific tRNA-guanine transglycosylase and further modified to queuosine. Isogenic pairs of Escherichia coli, containing or lacking the tRNA-transglycosylase (JE 7335, tgt+ lacZ+ and JE 7337, tgt- lacZ+; JE 7334, tgt+ lacZ- and JE 7336, tgt- lacZ-), have been employed to study the function of queuosine in tRNA. Compared with the tgt+ strain (JE 7335), the tgt- mutant (JE 7337) grown under anaerobic conditions, is defective with respect to the nitrate respiration system, in which electrons are transported from D(-)-lactate via quinone and cytochrome bNO3-(556) to nitrate. Low temperature cytochrome spectra of the anaerobically grown tgt- mutant show a lowered amount of type b cytochromes involving the spectrum of cytochrome bNO3-(556). In the case of the anaerobically grown tgt- mutant three proteins are missing in the protein pattern of cytoplasmic membranes. Their mol. wts. correspond to those of the subunits of the nitrate reductase complex. In contrast to the tgt+ strains (JE 7334, JE 7335) both tgt- mutants (JE 7336, JE 7337) cannot grow on lactate under anaerobic conditions with nitrate offered as electron acceptor and NO3- is not reduced to NO2-. A possible link between Q-modification of tRNAs, the synthesis of proteins of the nitrate reductase complex and the synthesis of menaquinone or ubiquinone is discussed.


Neurotic illness in the families of children with asthma and wheezy bronchitis: a general practice population study.
In a controlled population study 111 families of children with asthma and wheezy bronchitis were screened. The mothers of asthmatics suffered more depressive illness than controls. This correlates with the severity of the child's asthma. There was no difference in immunological status between depressive and non-depressive mothers of asthmatics.


Chronic cough and tachycardia-induced cardiomyopathy in a patient with idiopathic frequent, monomorphic premature ventricular contractions.
A 70-year-old woman presented with a 1-year history of dry cough. Extensive work-up ruled out common causes of chronic cough. She was found to have very frequent, monomorphic premature ventricular contractions (PVCs) and mild-to-moderate left ventricular systolic dysfunction. Propafenone 450 mg/day resulted in complete resolution of her cough and disappearance of PVCs within 24 hours of initiation. One month after the initiation of propafenone therapy, left ventricular ejection fraction normalized and her chronic cough resolved completely.


Optimal transport of vector measures.
We develop and study a theory of optimal transport for vector measures. We resolve in the negative a conjecture of Klartag, that given a vector measure on Euclidean space with total mass zero, the mass of any transport set is again zero. We provide a counterexample to the conjecture. We generalise the Kantorovich-Rubinstein duality to the vector measures setting. Employing the generalisation, we answer the conjecture in the affirmative provided there exists an optimal transport with absolutely continuous marginals of its total variation.


Congenital malformations caused by Stryphnodendron fissuratum (Leg. Mimosoideae) in guinea pigs (Cavia porcellus).
The aim of this study was to evaluate the toxicity of Stryphnodendron fissuratum pods in guinea pigs (Cavia porcellus) and test the hypothesis that this plant has teratogenic effects. Thus, sixteen guinea pigs were randomly divided into four groups of four animals each. Groups 10, 20 and 40 consisted of guinea pigs that received commercial food that contained crushed pods of S. fissuratum at concentrations of 10, 20 and 40 g/kg, respectively, during the period of organogenesis. Control group consisted of guinea pigs under the same management conditions that did not receive crushed pods of S. fissuratum in their food. In all experimental groups, the main clinical signs of poisoning consisted of anorexia, prostration, absence of vocalizations, alopecia, diarrhea, and abortions within the adult guinea pigs. Those that did not abort gave birth to weak, malnourished pups, some of which had fetal malformations. The main teratogenic changes consisted of eventration, arthrogryposis, amelia of the forelimbs, anophthalmia, microphthalmia, anotia and agnathia. The reductions in the number of offspring and the malformations observed in the experimental groups suggest that S. fissuratum affects fetal development and is teratogenic.


Revised Trauma Score and CRAMS better predicted mortality in high-energy-trauma patients than Early-Warning Score.
Trauma is one of the common reasons for emergency department (ED) presentations. Specifically, severe-trauma patients often present with mortal complications, including traumatic shock or respiratory or multiorgan failure/dysfunction, and these situations cause high-mortality risk. Scoring systems in the triage of trauma patients can help determine the injury's severity and the patient's prognosis. In this study, we aimed to compare Early-Warning Score (EWS), Revised Trauma Score (RTS), and CRAMS to predict the severity and prognosis of damage among high-energy-trauma patients. This retrospective study included adult high-energy-trauma patients (> 18 years of age) assessed in our emergency department (ED) from April 1, 2020, to September 31, 2020. We included a total of 177 high-energy-trauma patients in the study. We compared the effectiveness of EWS; RTS; and circulation, respiration, abdomen, motor, and speech (CRAMS) in predicting mortality. The primary outcome of this study was mortality. We included 67 females and 110 males with a mean age of 39.2 in our study. Of those patients, 6 died during ICU hospitalization and 104 were discharged from the ward. RTS (AUC: 0.978, CI: 0.945-0.994, p < 0.001) and CRAMS (AUC: 0.978, CI: 0.944-0.994, p < 0.001) had the same AUC values, but the AUC value of EWS (AUC: 0.966, CI: 0.927-0.987, p < 0.001) was lower. Sensitivity of EWS was 93.1 (CI: 77.2-99.2%), and sensitivity of RTS was 96.55 (CI: 82.2-99.9) and CRAMS' sensivity was 96.55% (CI: 82.2-99.9). RTS showed the highest specivity level (96.62%, CI: 92.3-98.9). In conclusion, RTS and CRAMS better predicted mortality in high-energy-trauma patients than EWS.


'Bowls are boring': Investigating enrichment feeding for pet dogs and the perceived benefits and challenges.
Canine enrichment feeding (CEF) is recommended by canine professionals, yet research into its use by dog owners is absent. This study is the first to investigate who uses CEF and the perceived benefits and barriers. A cross-sectional survey advertised in July and August 2021 received 1750 usable responses about owner and dog demographics, feeding methods used, canine quality of life and behaviour (Mini-Canine Behavioural Assessment and Research Questionnaire [C-BARQ]). Kongs, chews and activity toys were the most popular forms of CEF. CEF was most often used for a treat, delivering meals and keeping dogs busy. Owners not using CEF were more likely to be male and older. Dogs not fed using CEF were more likely to be older, of working type and have lower exercise needs. Furthermore, they were less likely to show meal interest, dog-directed fear or training difficulties. A common perceived benefit was mental stimulation; however, lack of time was commonly perceived to be a barrier. Certain feeding methods were associated with perceptions of reduced hunger and begging. The survey methodology means there is a risk of selection bias and conclusions cannot be drawn about causation. CEF was perceived by most owners to benefit behavioural problems and reduce food seeking. Further research using experimental research designs is required to establish causality.


The changing signs of congenital hip dislocation.
A total of 36 patients (42 hips) with frank congenital hip dislocation were studied. The initial clinical and x-ray signs were evaluated according to the age at which the patient was first seen and treatment started.


UV-visible spectral identification of the solution-phase and solid-phase permanganate oxidation reactions of thymine acetic acid.
Solution-phase and solid-phase permanganate oxidation reactions of thymine acetic acid were investigated by spectroscopy. The spectral data showed the formation of a stable organomanganese intermediate, which was responsible for the rise in the absorbance at 420 nm. This result enables unambiguous interpretation of the absorbance change at 420 nm, as the intermediate permanganate ions could be isolated on the solid supports.


Titania/reduced graphene oxide nanocomposites (TiO2/rGO) as an efficient photocatalyst for the effective degradation of brilliant green in aqueous media: effect of peroxymonosulfate and operational parameters.
This study is focused on synthesis of highly efficient Titania/reduced Graphene Oxide (TiO2/rGO) nanocomposites by means of simple hydrothermal technique. The TiO2/rGO were synthesized in different ratios of 0.5, 1.0, 2.0, and 3% by varying the concentration of rGO while the concentration of TiO2 was kept constant and the obtained samples were designated as TrG0.5, TrG1, TrG2, and TrG3 respectively. Different characterization techniques (SEM, TEM, HRTEM, XRD, EDX, TGA, UV-DRS, PL, EIS, and BET) showed high crystallinity, small crystallite size (18.4 nm), high thermal stability, high purity, low band gap energy (Eg = 3.12 eV), and high surface area (65.989 m2/g) for the as-synthesized TiO2/rGO nanocomposite. The efficiencies of TiO2/rGO were determined in terms of brilliant green (BG) dye degradation in aqueous media under UV light. The results revealed that 2% TiO2/rGO (TrG2) showed high efficiency for BG degradation with the kapp of 0.023 min-1 compared to TiO2 alone (kapp of 0.006 min-1). The rate of BG degradation was further synergised by the addition of peroxymonosulfate (PMS) to the system. The degradation of BG was improved to 99.4% by the incorporation of PMS in aqueous media compared to TrG2 alone. Furthermore, the degradation of BG was also examined in various media (neutral, acidic, and basic). The results revealed that by increasing pH of the medium from 3.85 to 8.2 the degradation of BG was enhanced from 99.4 to 99.9% with the corresponding kapp of 0.0602 min-1. Moreover, the photocatalytic degradation of BG followed the pseudo-first-order kinetics. Radical scavenging experiments showed that ●OH and SO4●- were the main species responsible for the degradation of BG under UV light. Besides, for determining the efficiency of as-synthesized TrG2/PMS system, the degradation of BG was also performed in various water types (distilled water, tape water, synthetic wastewater, and industrial wastewater). The degradation products (DPs) of BG and their corresponding pathways were proposed, accordingly.


Physical and Psychosocial Burden of Psoriatic Arthritis: Longitudinal Data From a Population-Based Study in Norway.
Psoriatic arthritis (PsA) can have a significant impact on health-related quality of life (HRQoL). Data on the timing of changes in the HRQoL of patients with PsA are limited. The present study was undertaken to explore associations between sleep disturbance, fatigue, pain, anxiety, depression, general health status, and satisfaction with life before and after a diagnosis of PsA compared to the general population. Patients diagnosed with PsA between the Nord-Trøndelag Health Study (HUNT2 [1995-1997] and HUNT3 [2006-2008]) surveys were compared to the general population. The adjusted odds ratio (ORadj ) with 95% confidence interval (95% CI) was estimated at both time points. Among 36,507 individuals participating in both the HUNT2 and HUNT3 surveys, 160 were diagnosed with PsA between the surveys. The prevalence of sleep disturbances and fatigue was higher in PsA patients after diagnosis compared to the general population (ORadj 2.24 [95% CI 1.55-3.25] and ORadj 1.94 [95% CI 1.27-2.98], respectively). The prevalence of pain and poor health status were higher in patients with PsA compared with the general population even before PsA was diagnosed (ORadj 2.81 [95% CI 1.96-4.02] and ORadj 3.08 [95% CI 2.19-4.35], respectively) and increased after diagnosis of PsA (ORadj 12.87 [95% CI 6.27-26.40] and ORadj 5.63 [95% CI 3.99-7.95], respectively). For anxiety, depression, and life satisfaction, patients who developed PsA were comparable to the general population both before and after the diagnosis of PsA. Compared to the general population, PsA patients reported a higher prevalence of pain and poorer health status before diagnosis. Increased prevalence of sleep disturbances and fatigue in PsA patients was only found after the PsA diagnosis, and no differences between patients with PsA and the control group were found for anxiety and depression.


Anti-allergic activity of formoterol, a new beta-adrenoceptor stimulant, and salbutamol in human leukocytes and human lung tissue.
Formoterol and salbutamol were compared for in vitro inhibition of allergen-induced histamine release from allergic leukocytes and human lung tissue passively sensitized with allergic serum. Formoterol inhibited the release of histamine from leukocytes but salbutamol showed little inhibiting effect. When combined with theophylline, formoterol was a more potent inhibitor of the release of histamine from leukocytes in allergic patients than salbutamol. In fragments of human lung sensitized with allergic serum, the concentration required to inhibit histamine release by 50% was 2 x 10(-11) M for formoterol and 8.5 x 10(-9) M for salbutamol. The potency of salbutamol and formoterol in blocking specific 3H-dihydroalprenolol binding to beta-adrenoceptors on guinea pig lung membranes revealed that formoterol had higher affinity for beta-adrenoceptors than salbutamol, and the concentration required for half-maximum stimulation of adenylate cyclase was approximately 200-fold higher for salbutamol than for formoterol.


Aggressive Intra-Abdominal Fibromatosis in an Adolescent Girl - An Unusual Sequelae to Ovarian Germ Cell Tumor.
Abdominal fibromatosis presenting as an abdominal mass is a rare occurrence in a gynecological setting. The diagnosis might not be suspected preoperatively, and management could be challenging. An 18-year-old girl with ovarian germ cell malignancy was managed with staging laparotomy and chemotherapy. She developed a large abdominal mass 10 months later. An abdominopelvic mass (40 × 20 cm) was removed at laparotomy. The histopathological diagnosis was intra-abdominal fibromatosis. A rapidly growing abdominal mass recurred postoperatively. After discussion with the tumor board, chemotherapy with methotrexate and vinblastine was started. The tumor was not responsive, and the patient succumbed after the second cycle of chemotherapy. Abdominal fibromatosis should be considered among the differential diagnoses of a rapidly growing abdominal mass after resection of an ovarian germ cell tumor.


Interactions of HIV and methamphetamine: cellular and molecular mechanisms of toxicity potentiation.
Methamphetamine (METH) is a highly addictive psychostimulant drug, whose abuse has reached epidemic proportions worldwide. METH use is disproportionally represented among populations at high risks for developing HIV infection or who are already infected with the virus. Psychostimulant abuse has been reported to exacerbate the cognitive deficits and neurodegenerative abnormalities observed in HIV-positive patients. Thus, the purpose of the present paper is to review the clinical and basic observations that METH potentiates the adverse effects of HIV infection. An additional purpose is to provide a synthesis of the cellular and molecular mechanisms that might be responsible for the increased toxicity observed in co-morbid patients. The reviewed data indicate that METH and HIV proteins, including gp120, gp41, Tat, Vpr and Nef, converge on various caspase-dependent death pathways to cause neuronal apoptosis. The role of reactive microgliosis in METH- and in HIV-induced toxicity is also discussed.


Antioxidant Action of Apelin-12 Peptide and Its Structural Analog In Vitro.
The effects of C-terminal fragment of natural peptide apelin-12 H-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe-OH (A12) and its structural analog H-(N(α)Me)Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Nle-Pro-Phe-OH (AI) on Cu(2+)-induced free radical oxidation of low-density lipoprotein in human blood plasma and activity of commercially available enzymes superoxide dismutase and catalase in a concentration range of 0.01-1 mM were examined. A12 and AI had no effect on superoxide dismutase and catalase activities during 24-h co-incubation with these enzymes at 4°C. When used in a concentration of 1 mM, A12 and AI decreased the maximum low-density lipoprotein oxidation rate by 51 and 47%, respectively, and lengthened the lag phase of low-density lipoprotein oxidation by 2.6 and 1.8 times, respectively, which confirmed their antioxidant potency.


Radiotherapy alone in carcinoma of the intact uterine cervix according to G. H. Fletcher guidelines: a French cooperative study of 1383 cases.
A French Cooperative study of 1383 cases with invasive carcinoma of the intact uterine cervix treated with radiation therapy alone, using the guidelines provided by G. H. Fletcher led to the following conclusions: The techniques of treatment were easily reproducible in 9 French centers, working in a prospective cooperative study; Results similar to those of the original study were achieved in Stages I and IIA (MDAH substaging) with a locoregional failure rate of 7%; In Stage IIB, the locoregional failure rate of 16% is also comparable in both studies; Locoregional failures in Stage III are slightly lower than those reported in Houston, probably reflecting differences in patient's prognostic factors in France and Texas; The 5-year survival rate obtained in advanced Stages (UICC FIGO staging) are among the highest in the literature (76% in Stage IIb, 62% in Stage IIIa and 50% in Stage IIIb); The rate of severe complications remains acceptable and decreased throughout the study thanks to a better use of computer dosimetry.


Synthesis of α-(Trifluoromethyl)styrenes and 1,3-Di(trifluoromethyl)indanes via Electrophilic Activation of TMS Ethers of (Trifluoromethyl)benzyl Alcohols in Brønsted Acids.
TMS ethers of CF3-benzyl alcohols (and their heterocyclic analogues) undergo elimination of TMSOH molecule with the formation of α-(trifluoromethyl)styrenes in yields of up to 90% under the action of strong Brønsted acids TfOH or H2SO4. Under the acidic conditions upon prolongation of the reaction, the α-(trifluoromethyl)styrenes are further dimerized into cis-/trans-1,3-di(trifluoromethyl)indanes in yields of up to 100%. Plausible reaction mechanisms of these electrophilic transformations including the intermediate formation of CF3-benzyl carbocations are discussed.


Coping with Stress During the COVID-19 Outbreak: The Contribution of Self-Control Skills and Religiosity in Arab Israeli-Palestinian Students in Israel.
The reported high rates of deaths and negative psychological outcomes of the Coronavirus (COVID-19) pandemic have led to an increased empirical interest in examining the contributing factors of coping during the COVID-19 pandemic. Adolescents living in Arab societies have unique challenges that may increase the likelihood of exhibiting symptoms of stress during this crisis. However, this population has been understudied in this context. The current research aims to elucidate factors that may contribute to Arab Israeli-Palestinian students' coping abilities during the COVID-19 pandemic by investigating the relationship between coping with stress during the COVID-19 outbreak and both self-control and religiosity. To our knowledge, the present study is the first to investigate the relationship of coping with stress during the COVID-19 outbreak with self-control skills and religiosity among Arab Israeli-Palestinian college students in Israel (n = 465). Correlational analyses and stepwise multiple regression models were used to examine these relationships. The stepwise multiple regression model demonstrated that (1) higher levels of self-control (β = .19, p < .01) and religiosity (β = .16, p < .01) predicted higher levels of adaptive, problem-focused coping, and (2) higher levels of self-control (β = -.21, p < .01) and religiosity (β = -.17, p < .01) predicted lower levels of maladaptive, emotion-focused coping. Thus, the current research demonstrates the importance of these variables in countering stress resulting from the COVID-19 outbreak in non-Western societies. These findings are consistent with previous literature that has addressed the impact of self-control and religiosity in improving coping behaviours in Western societies.


Developing and pilot-testing a Finding Balance Intervention for older adult bereaved family caregivers: A randomized feasibility trial.
This study aimed to test the feasibility of a psychosocially supportive writing intervention focused on finding balance for older adult bereaved family caregivers of advanced cancer patients. The Finding Balance Intervention (FBI) was tested for feasibility, acceptability and potential influence on increasing hope, coping and balance through a multi-method pilot study employing a randomized trial design with 19 older adults with an average age of 72 years. The intervention group received the FBI and a follow up visit from an RN-RA. The control group received the FBI at a second visit. The FBI, a theory-based intervention was developed from grounded theory qualitative data, applying Delphi methods to design a self-administered, psychosocially supportive, writing intervention for older adults who had lost a spouse after caregiving. Feasibility was assessed and specific modifications identified. The FBI was easy to use, acceptable and of benefit. The FBI offered validation of emotions and ways to discover new ideas to find balance, which may enable bereaved caregivers to move forward on a unique journey through grief. The treatment group showed a statistically significant increase in restoration-oriented coping and higher oscillation activity. The results suggest the FBI was easy to use, acceptable and of benefit. A full scale study, with specific modifications to the design, is needed to test the effectiveness of this innovative intervention.


Spontaneous uterine rupture with fatal hemoperitoneum due to placenta accreta percreta: a case report and review of the literature.
Placenta accreta percreta is an unusual cause of hemoperitoneum. Less than 50 such cases have been reported in the English-language literature over the past 100 years. A 22-year-old pregnant multigravida woman who had spontaneous uterine rupture with exsanguination caused by this entity is described. She had abdominal pain and cardiovascular collapse and died without a premortem diagnosis.


Regulation of isoleucine-valine biosynthesis in Saccharomyces cerevisiae.
The threonine deaminase gene (ILV1) of Saccharomyces cerevisiae has been designated "multifunctional" since Bollon (1974) indicated its involvement both in the catalysis of the first step in isoleucine biosynthesis and in the regulation of the isoleucine-valine pathway. Its role in regulation is characterized by a decrease in the activity of the five isoleucine-valine enzymes when cells are grown in the presence of the three branched-chain amino acids, isoleucine, valine and leucine (multivalent repression). We have demonstrated that the regulation of AHA reductoisomerase (encoded by ILV5) and branched-chain amino acid transaminase is unaffected by the deletion of ILV1, subsequently revealing that the two enzymes can be regulated in the absence of threonine deaminase. Both threonine deaminase activity and ILV1 mRNA levels increase in mutants (gcd2 and gcd3) having constitutively depressed levels of enzymes under the general control of amino acid biosynthesis, as well as in response to starvation for tryptophan and branched-chain amino acid imbalance. Thus, the ILV1 gene is under general amino acid control, as is the case for both the ILV5 and the transaminase gene. Multivalent repression of reductoisomerase and transaminase can be observed in mutants defective in general control (gcn and gcd), whereas this is not the case for threonine deaminase. Our analysis suggests that repression effected by general control is not complete in minimal medium. Amino acid dependent regulation of threonine deaminase is only through general control, while the branched-chain amino acid repression of AHA reducto isomerase and the transaminase is caused both by general control and an amino acid-specific regulation.


Identification and pattern of expression of a developmental isoform of troponin I in chicken and rat cardiac muscle.
A monoclonal antibody that reacts with all known isoforms of troponin I detected a single isoform of cardiac troponin I in both atrial and ventricular chambers of adult chicken and rat hearts in an immunoblotting analysis. Another isoform of troponin I in addition to the adult cardiac form, however, was present in all chambers of the heart during early development in both species. This developmental isoform appeared to have the same electrophoretic mobility on SDS tris glycine polyacrylamide gels as that observed for the adult slow skeletal muscle isoform. In the rat, only the developmental isoform of troponin I was present in the early foetal heart and small amounts of the adult cardiac isoform were not apparent until late in gestation, whereas the developmental and adult isoforms were expressed in approximately equal amounts throughout embryonic development in the chicken. The level of developmental isoform of troponin I in both the chicken and the rat hearts gradually decreased so that only small amounts of this variant were detectable two weeks after birth or post hatching.


Optimisation of methodology for whole genome sequencing of Measles Virus directly from patient specimens.
In an era of decreasing genetic diversity of Measles Virus (MeV), effective surveillance requires a higher-resolution genotyping method or whole genome sequencing (WGS) to document elimination. Through optimization of MeV WGS protocol, we developed a MeV-specific probe enrichment method that allows next generation sequencing from clinical specimens. With the probe enrichment method, 70% of specimens can be sequenced at a read depth of greater than 10 reads with minimal off-target sequences.


Antibody responses to hepatitis A virus vaccination in thai hiv-infected children with immune recovery after antiretroviral therapy.
The prevalence of hepatitis A virus (HAV) protective antibody in 98 Thai HIV-infected children who achieved immune recovery after antiretroviral therapy was 12.2%. After a 2-dose HAV vaccination, 98.8% (85 of 86 children) seroconverted. The geometric mean titer was 520.95 mIU/mL. In a multivariate analysis, female gender, age < 12 years and higher CD4 lymphocyte count at enrollment were predicting factors for high (≥ 250 mIU/mL) HAV antibody response.


In vitro estradiol synthesis and secretion by tadpole ovaries of different developmental stages.
The tadpole ovaries at TK stage XIX can synthesize and secrete estradiol (E2), yet it is unknown when this ovarian function starts and how it develops. To this end, the present work has been carried out. The ovaries of different developmental stages of tadpoles and young frogs of Rana catesbeiana were taken, cut into small pieces, and incubated for 6 hr at 20 degrees in Krebs-Ringer bicarbonate buffer. The media were then analyzed for E2 by radioimmunoassay. The results indicate that the tadpoles synthesize and release E2 as early as stage X, that E2 increases slowly and gradually through stage XXV, and that E2 increases rapidly in juvenile frogs. This trend of growth of the ovarian function in estradiol secretion in vitro is in accordance with that reported for female chick embryos. There exists the possibility that the growth of E2 secretion could be biphasic, one with slow increment of autonomous E2 secretion at early stages and the other with quick increase due to pituitary stimulation at the stage of metamorphic climax.


Using the Delphi process to determine the minimum clinically important effect size for the Balanced-2 randomised controlled trial.
The sample size calculation is an important step in designing randomised controlled trials. For a trial comparing a control and an intervention group, where the outcome is binary, the sample size calculation requires choosing values for the anticipated event rates in both the control and intervention groups (the effect size), and the error rates. The Difference ELicitation in TriAls guidance recommends that the effect size should be both realistic, and clinically important to stakeholder groups. Overestimating the effect size leads to sample sizes that are too small to reliably detect the true population effect size, which in turn results in low achieved power. In this study, we use the Delphi approach to gain consensus on what the minimum clinically important effect size is for Balanced-2, a randomised controlled trial comparing processed electroencephalogram-guided 'light' to 'deep' general anaesthesia on the incidence of postoperative delirium in older adults undergoing major surgery. Delphi rounds were conducted using electronic surveys. Surveys were administered to two stakeholder groups: specialist anaesthetists from a general adult department in Auckland City Hospital, New Zealand (Group 1), and specialist anaesthetists with expertise in clinical research, identified from the Australian and New Zealand College of Anaesthetist's Clinical Trials Network (Group 2). A total of 187 anaesthetists were invited to participate (81 from Group 1 and 106 from Group 2). Results from each Delphi round were summarised and presented in subsequent rounds until consensus was reached (>70% agreement). The overall response rate for the first Delphi survey was 47% (88/187). The median minimum clinically important effect size was 5.0% (interquartile range: 5.0-10.0) for both stakeholder groups. The overall response rate for the second Delphi survey was 51% (95/187). Consensus was reached after the second round, as 74% of respondents in Group 1 and 82% of respondents in Group 2 agreed with the median effect size. The combined minimum clinically important effect size across both groups was 5.0% (interquartile range: 3.0-6.5). This study demonstrates that surveying stakeholder groups using a Delphi process is a simple way of defining a minimum clinically important effect size, which aids the sample size calculation and determines whether a randomised study is feasible.


Monte Carlo calculation of beam quality correction factors in proton beams using detailed simulation of ionization chambers.
This work calculates beam quality correction factors (kQ) in monoenergetic proton beams using detailed Monte Carlo simulation of ionization chambers. It uses the Monte Carlo code penh and the electronic stopping powers resulting from the adoption of two different sets of mean excitation energy values for water and graphite: (i) the currently ICRU 37 and ICRU 49 recommended Iw = 75 eV and Ig = 78 eV and (ii) the recently proposed Iw = 78 eV and Ig = 81.1 eV. Twelve different ionization chambers were studied. The k Q factors calculated using the two different sets of I-values were found to agree with each other within 1.6% or better. k Q factors calculated using current ICRU I-values were found to agree within 2.3% or better with the k Q factors tabulated in IAEA TRS-398, and within 1% or better with experimental values published in the literature. k Q factors calculated using the new I-values were also found to agree within 1.1% or better with the experimental values. This work concludes that perturbation correction factors in proton beams--currently assumed to be equal to unity--are in fact significantly different from unity for some of the ionization chambers studied.


Emergence of carbapenemases in Gram-negative bacteria in Hamburg, Germany.
We analyzed a collection of carbapenem-resistant Gram-negative bacterial isolates and detected VIM-1, VIM-2, and KPC-2 in diverse enterobacterial species and Pseudomonas aeruginosa isolates. Our findings suggest a more widespread dissemination of carbapenemases in Germany than currently appreciated.


An experimental evaluation of antiseptic wound irrigation.
An experimental wound infection model was used to assess the value of four proprietary antiseptics applied topically in preventing the development of wound sepsis. Irrigation of wounds with either saline or noxytiolin 15 min after contamination with Staphylococcus aureus did not reduce either the incidence or degree of infection. Benzalkonium chloride and, to a lesser degree, povidone-iodine significantly reduced the infection rate, but were inferior to chlorhexidine gluconate which eliminated all overt signs of infection. The rate of healing of the chlorhexidine-treated, contaminated wounds was found to be no different from control non-infected wounds. When irrigation was carried out 45 min before wounds were contaminated, chlorhexidine was the only treatment which reduced the rate of infection (P less than 0.001). It is concluded that the superior activity of chlorhexidine in this model is a good indication that it should be a highly effective agent in the prevention of staphylococcal wound infection, and that this is probably due to a combination of bactericidal and persistent action together with low toxicity.


Characteristic effects of taste-compounds on the dynamic behavior of oleate-monolayer.
Dynamic behavior of the monolayer of oleic acid on an aqueous solution was studied. The hysteresis loop of the surface, pressure (pi)-area (A) curve, was found to be characteristically dependent on the chemical stimuli with different taste-categories: salty, sweet, bitter and sour. The characteristic response of the dynamic surface behavior was discussed in relation with our recent finding, i.e., the features of the oscillation change in a different manner with the addition of various chemical species belonging to different taste categories in an excitable artificial liquid-membrane of oleic acid (Yoshikawa, et al, Langmuir, 4, 759-762 (1988).