Role of vitamin B12 and folate deficiencies in carcinogenesis.
A significant body of experimental evidence supports the notion that a deficiency of either vitamin B12 or folic acid enhances the activity of various carcinogens. Unifying mechanisms are proposed to explain this cocarcinogenic role.


Access of migrant gold miners to compensation for occupational lung disease: Quantifying a legacy of injustice.
A legacy of the South African gold mining industry, now in decline, is a large burden of silicosis and tuberculosis among former migrant miners from rural South Africa and surrounding countries, particularly Lesotho and Mozambique. This neglected population faces significant barriers in filing claims for compensation for occupational lung disease. The objective of the study was to gain insight into the extent of such barriers, particularly for former miners and cross-border migrants. The database of a large gold mining company and the statutory compensation authority were analyzed for the period 1973-2018 by country of origin, age, and employment status at the time of claim filing. Proportions and odds ratios (ORs) for each of the compensable diseases were calculated by the above variables. Processing delays of claims were also calculated. Annual company employment declined from 240,718 in 1989 to 43,024 in 2018 and the proportion of cross-border migrants within the workforce from 51.0 to 28.1%. The compensation database contained 68,612 claims. The majority of compensable claims in all diagnostic categories were from active miners. The odds of cross-border miners relative to South African miners filing a claim depended on employment status. For example, the OR for Lesotho miners filing while in active employment was 1.86 (95% CI 1.81, 1.91), falling to 0.94 (95% CI 0.91, 0.98) among former miners. The equivalent findings for Mozambiquan miners were 0.95 (95% CI 0.91, 1.00), falling to 0.44 (95% CI 0.41, 0.47). Median processing delays over the whole period were from 1.1 years from filing to adjudication, and 3.8 years from filing to payment. The findings provide a quantitative view of differential access to occupational lung disease compensation, including long processing delays, among groups of migrant miners from the South African gold mines. There is a deficit of compensable claims for silicosis and silico-tuberculosis among former miners irrespective of country of origin. While cross-border miner groups appear to file more claims while active, this is reversed once they leave employment. Current large-scale efforts to provide medical examinations and compensation justice to this migrant miner population need political and public support and scrutiny of progress.


[Long-term effects of rehabilitation of an outpatient "heart group". A case control study].
The effects of an outhospital cardiac rehabilitation program in "heart groups" (HG) are studied in a case-control design. The control group (KG) was collected by match-pairing from 12,560 cases of a rehabilitation clinic fitting in the relevant criteria to those of members of the HG. Patients of both groups (n = 75/group) after myocardial infarction and CABG were followed up over 7.5 years. There was no significant difference in risk factor modification. Exercise tolerance improved significantly in the HG by increasing maximum work capacity by 50% in spite of a mean age of 60 years at the beginning. Members of HG had significantly lesser cardiac complaints and lower need for cardiac medication. Cardiac morbidity was reduced by 54% and costs for medical care were lowered by 47% in HG. Although effects of secondary prevention on reducing risk factors were still insufficient, exercise tolerance in higher age and quality of life were improved, reduction in medication and in the morbidity saved costs for the health system.


A rare giant gastrointestinal stromal tumor of the stomach traversing the upper abdomen: a case report and literature review.
We present the case of a 66-year-old woman with a huge gastrointestinal stromal tumor of the stomach that traversed her upper abdomen. The predominant abdominal sign was a huge, palpable mass, but there were no other distinctive findings in her physical examination or her routine blood workup, including biochemical markers. It was difficult to judge the origin of the mass upon imaging. Furthermore, radiological findings revealed that the mass had a complex relationship with many major blood vessels. An exploratory laparotomy revealed a huge tumor protruding from the anterior wall of the stomach fundus, on the lesser curvature of the stomach, measuring approximately 21 × 34 × 11 cm in diameter and weighing 5.5 kg. A complete resection was performed and the tumor was characterized on immunohistochemistry as a gastrointestinal stromal tumor of the stomach. Preoperative diagnosis of gastrointestinal stromal tumors can be difficult, and we hope that the presentation of this rare case and literature review will benefit other diagnosing clinicians having similar problems.


Occurrence of excitatory dopaminoceptors in the rat and guinea-pig vas deferens.
1. Noradrenaline and dopamine produce contractions of isolated preparations of vasa deferentia from the rat or the guinea-pig. 2. Dopamine was three to five times as potent as noradrenaline on the rat vas deferens, but was considerably less potent than noradrenaline on the guinea-pig vas deferens. 3. Phentolamine antagonized responses to noradrenaline and dopamine of vasa deferentia of both species. On the rat vas deferens the pA2 values against noradrenaline and dopamine were 7.6 and 7.4, respectively. 4. Pimozide, a dopamine antagonist, antagonized responses to dopamine on vasa deferentia of both species, but was not significantly active in antagonizing responses to noradrenaline. On the rat vas deferens, the pA2 value against dopamine was 7.9. t. The beta-adrenoceptor blocking agents, propranolol and oxprenolol slightly enhanced dopamine-induced contractions on vasa deferentia of both species. 6. It is suggested that dopamine might act on both a-adrenoceptors and dopaminoceptors in the vas deferens, and that the component due to activation of dopaminoceptors is greater in the rat than the guinea-pig.


Amniotic growth factors enhanced human pre-adipocyte cell viability and differentiation under hypoxia.
One of the major drawbacks associated with autologous fat grafting is unpredictable graft retention. Various efforts to improve the survivability of these cells have been explored, but these methods are time-consuming, complex, and demand significant technical skill. In our study, we examine the use of cryopreserved amniotic membrane as a source of exogenous growth factors to improve adipocyte survivability under normal and hypoxic conditions. Human primary preadipocytes were cultured in a gelatin-ferulic acid (Gtn-FA) hydrogel with variable oxygen concentration and treated with amniotic membrane-derived condition medium (CM) for 7 days. This hydrogel provides a hypoxic environment and also creates a 3D cell culture to better mimic recipient site conditions. The O2 concentration in the hydrogel was measured by electron paramagnetic resonance oxygen imaging (EPROI). The conjugation of FA was confirmed by FTIR and NMR spectroscopy. The cell viability and adipocyte differentiation were analyzed by alamarBlue™ assay, Oil Red O staining, and RT-qPCR. The expression of genes: Pref-1, C/EBP β, C/EBP α, PPAR-ƴ, SLC2A4, and VEGF-A were quantified. The cell viability results show that the 50% CM showed significantly higher cell pre-adipocyte cell viability. In addition, compared to normal conditions, hypoxia/CM provided higher PPAR-ƴ (p < .05), SLC2A4, and VEGF-A (p < .05) (early and terminal differentiating markers) mRNA expression. This finding demonstrates the efficacy of amniotic CM supplementation as a novel way to promote adipocyte survival and retention via the expression of key gene markers for differentiation and angiogenesis.


Effects of Presentation Rate and Attention on Auditory Discrimination: A Comparison of Long-Latency Auditory Evoked Potentials in School-Aged Children and Adults.
Decoding human speech requires both perception and integration of brief, successive auditory stimuli that enter the central nervous system as well as the allocation of attention to language-relevant signals. This study assesses the role of attention on processing rapid transient stimuli in adults and children. Cortical responses (EEG/ERPs), specifically mismatch negativity (MMN) responses, to paired tones (standard 100-100 Hz; deviant 100-300 Hz) separated by a 300, 70 or 10 ms silent gap (ISI) were recorded under Ignore and Attend conditions in 21 adults and 23 children (6-11 years old). In adults, an attention-related enhancement was found for all rate conditions and laterality effects (L>R) were observed. In children, 2 auditory discrimination-related peaks were identified from the difference wave (deviant-standard): an early peak (eMMN) at about 100-300 ms indexing sensory processing, and a later peak (LDN), at about 400-600 ms, thought to reflect reorientation to the deviant stimuli or "second-look" processing. Results revealed differing patterns of activation and attention modulation for the eMMN in children as compared to the MMN in adults: The eMMN had a more frontal topography as compared to adults and attention played a significantly greater role in childrens' rate processing. The pattern of findings for the LDN was consistent with hypothesized mechanisms related to further processing of complex stimuli. The differences between eMMN and LDN observed here support the premise that separate cognitive processes and mechanisms underlie these ERP peaks. These findings are the first to show that the eMMN and LDN differ under different temporal and attentional conditions, and that a more complete understanding of children's responses to rapid successive auditory stimulation requires an examination of both peaks.


Correlation of hydrogen exchange behaviour and thermal stability of lysozyme.
The solvent exchange rates of individual indole NH hydrogens of tryptophan residues of lysozyme have been measured, by using 1H nuclear magnetic resonance spectroscopy, as a function of temperature in the presence of urea and following chemical modification. The results have been interpreted in terms of a low activation energy process which is not dependent on the thermal stability of the protein, and a higher activation energy process that is directly correlated with the thermal stability. The significance of these observations for an understanding of the dynamics of the protein is discussed.


Understanding the molecular basis of anorexia and tissue wasting in cancer cachexia.
Cancer cachexia syndrome is a major cause of morbidity and mortality in cancer patients in the advanced stage. It is a devastating disorder characterized by nutritional impairment, weakness, and wasting, and it affects treatment success and quality of life. Two major symptoms of cancer cachexia are anorexia and weight loss. Weight loss in cachexia is not reversed through increased food intake, suggesting that anorexia and weight loss in cancer patients are regulated by independent molecular mechanisms. Although the wasting phenotype mostly occurs in skeletal muscle and adipose tissue, other organs, such as the brain, liver, pancreas, heart, and gut, are also involved in cachexia. Thus, cachexia is a multiorgan syndrome. Although the molecular basis of cancer cachexia-induced weight loss is known, the mechanism underlying anorexia is poorly understood. Here, we highlight our recent discovery of a new anorexia mechanism by which a tumor-derived humoral factor induces cancer anorexia by regulating feeding-related neuropeptide hormones in the brain. Furthermore, we elucidated the process through which anorexia precedes tissue wasting in cachexia. This review article aims to provide an overview of the key molecular mechanisms of anorexia and tissue wasting caused by cancer cachexia.


Later-onset rheumatoid factor negative polyarticular juvenile idiopathic arthritis (JIA): a unique patient group?
To determine the two-year outcome of patients with later-onset polyarticular rheumatoid factor (RF) negative (-) juvenile idiopathic arthritis (JIA), and predictors of outcome. All patients ages 10 to16 years diagnosed and followed in the Rheumatology Clinic at SickKids Hospital with the diagnosis of polyarticular RF- JIA were eligible for study. A retrospective chart analysis was performed and number of active joints, medications, laboratory information and childhood health assessment questionnaire scores were recorded at diagnosis, and 6, 12, and 24 months following diagnosis. As early as 6 months after diagnosis the mean number of active joints decreased from 16 to < 10, with 50% of the patients having < 5 active joints. The predominant joints affected were the wrist, knee, and small joints of the hand. The only predictor of active joint count at the 2-year follow-up was initial presenting active joint count as classified as mild, moderate, or severe. Sex, age, and laboratory results at presentation did not show any correlation with active joint count at 2 years. Majority of patients were treated with non-steroidal anti-inflammatory drugs (98%) and at least one disease-modifying anti-rheumatic drug (56%). The two-year outcome of patients with late-onset RF- polyarticular JIA was very good with the majority of patients having minimally active disease at last follow-up. Presence of significant polyarthritis at presentation was the only feature associated with long-term joint activity. Sex and lab results did not show any correlation with active joint in this cohort of RF-JIA patients.


Inflammatory and glandular skin disease in pregnancy.
A switch from cell-mediated to humoral immunity (helper T 1 [Th1] to helper T 2 [Th2] shift) during gestation plays a key role in placental immune tolerance. As a result, skin diseases that are Th2 mediated often worsen, whereas skin diseases that are Th1 mediated often improve during gestation. Also, due to fluctuations in glandular activity, skin diseases involving sebaceous and eccrine glands may flare, whereas those involving apocrine glands may improve during pregnancy. Despite these trends, inflammatory and glandular skin diseases do not always follow the predicted pattern, and courses are often diverse. We review the gestational course of inflammatory skin diseases, such as atopic dermatitis (atopic eruption of pregnancy), psoriasis, impetigo herpetiformis, urticaria, erythema annulare centrifugum, pityriasis rosea, sarcoidosis, Sweet syndrome, and erythema nodosum, as well as glandular skin diseases, including acne vulgaris, acne rosacea, perioral dermatitis, hidradenitis suppurativa, Fox-Fordyce disease, hyperhidrosis, and miliaria. For each of these diseases, we discuss the pathogenesis, clinical presentation, and management with special consideration for maternal and fetal safety.


Total agenesis of the corpus callosum in a patient with childhood-onset schizophrenia.
The hypothesis that schizophrenia involves aberrant inter-hemispheric communication has a long pedigree, however its precise role remains unclear. We therefore report the case of a total agenesis of the corpus callosum in a 21-year-old man with childhood-onset schizophrenia. The presence of schizophrenia with very early onset on absence of corpus callosum offers an opportunity to examine neurodevelopmental model and theories regarding to interhemispheric communication in the pathogenesis of psychosis.


Movement hyperacuity in childhood amblyopia.
Amblyopia results in deficits in a number of visual functions in both the amblyopic and dominant eye. The present work describes oscillatory movement displacement thresholds (OMDT) in childhood amblyopia. The OMDT from the dominant and amblyopic eyes of 50 orthoptic patients (aged 74 (SD 16) months) were compared with those from a group of 24 controls (79 (21) months). OMDT were measured using a forced choice staircase procedure. Subjects were asked to identify which of the computer controlled monitors displayed the oscillating stimulus. Visual acuity and stereoscopic responses were noted from clinical records. Amblyopic children demonstrating stereopsis showed no significant OMDT deficit in the amblyopic eye. Those children having no stereopsis had elevated OMDT in the amblyopic eye (p < 0.05). Results suggest that the dominant eye of children with amblyopia may also have a pattern of visual development which is anomalous (difference in correlation coefficient with age; p < 0.05). OMDT deficits demonstrated in some amblyopic eyes indicate that amblyopia is incompletely described by its "clinical" definition. Results suggest that the dominant eye in those with unilateral amblyopia may not be "normal".


Advances and prospects on biosynthesis, structures and functions of venom proteins from parasitic wasps.
Molecular and biochemical properties of parasitoid Hymenoptera's venom proteins are currently receiving an increasing interest. In this review, we will highlight the progress that has been made over the past 10 years in fundamental research on this field. Main knowledge acquired on the structural features of parasitoid venom peptides, proteins and enzymes will be summarized and discussed and several examples showing the diversity of their biological functions will be given with respect to future prospects and applications.


2'-deoxycytidine in free nucleosides and double-stranded DNA as the major target of lipid peroxidation products.
Lipid peroxidation generates a variety of reactive products that covalently modify DNA, yielding several types of adducts with nucleobases. In the present study, we characterized the modification of nucleobases during peroxidation of linoleate and found that 2'-deoxycytidine (dC) could be a major target of the modification by lipid peroxidation reactions. Upon incubation with oxidized linoleate, dC and 2'-deoxyguanosine (dG) were significantly modified among four 2'-deoxynucleosides. The major product in dG/linoleate was identical to the 2-oxo-heptyl-substituted 1,N(2)-etheno-dG that had been previously identified as a 4-oxo-2-nonenal (ONE)-dG adduct. On the basis of spectroscopic and chemical characterization, we identified the major product in dC/linoleate as the 2-oxo-heptyl-substituted 3,N(4)-etheno-dC. The same adduct was also produced upon reaction of dC with ONE, suggesting that ONE might represent the major reactive species that modifies DNA during lipid peroxidation. Indeed, this proposition was supported by the observation that ONE was far more reactive with dC and dG than other genotoxic aldehydes, such as 4-hydroxy-2-nonenal. More strikingly, we found that, in contrast to the similar reactivity of ONE toward free nucleobases (dC and dG), ONE preferentially reacted with dC residues in double-stranded DNA. These results suggest that ONE and other 4-oxo-2-alkenals may possess by far the strongest electrophilic potential vs. dC and that the formation of 4-oxo-2-alkenal-adducted dC may thus serve as one mechanism for oxidative damage to DNA in vivo.


Suspected clindamycin-associated oesophageal injury in cats: five cases.
The clinical findings, treatment and outcome of suspected clindamycin-associated oesophageal injury in five cats are reported. All cats were treated with one 75 mg clindamycin capsule twice daily (dose range 12-19 mg/kg). Capsules were administered without food or a water bolus. Dysphagia, regurgitation, choking or gagging were seen 3-9 days after starting clindamycin. On oesophagoscopy, three cats had oesophagitis, one of which progressed to stricture formation. Two cats had an oesophageal stricture at first presentation. This is the first report of suspected clindamycin-associated oesophageal injury in cats. It serves to further alert practitioners to the potential for drug-induced oesophageal disorders (DIOD) in cats treated with oral medications and to urge prevention by promoting a change in dosing practices.


[Laryngomalacia. When does surgery make sense?].
The most common cause of stridor in newborns is instability of the upper larynx, called laryngomalacia. In approximately 10% of children normal development is impaired. The diagnostics and therapy must follow a clear plan that is also comprehensible to the parents. The obstruction should be localized endoscopically, the anatomical characteristics determined, and the surgical possibilities evaluated. Additional pathological changes of the upper airway (e.g., vocal fold paresis) need to be excluded. Surgery for laryngomalacia, called supraglottoplasty, allows reduction of excess mucus, transectioning of aryepiglottic folds that are too short, and in some cases epiglottic fixation to the base of the tongue. In extreme cases tracheotomy is unavoidable. Surgery is only recommended for severe cases; when carried out correctly according to the medical indications, the success rate is over 90%.


On the effects of a chronic deoxynivalenol intoxication on performance, haematological and serum parameters of pigs when diets are offered either for ad libitum consumption or fed restrictively.
Wheat infected naturally with Fusarium, contaminated mainly with deoxynivalenol (DON) (16.6 mg DON/kg), was added to a total constant wheat content of 400 g/kg diet. To distinguish between differences in feed intake and specific effects of the DON contaminated diet, control and DON contaminated feed was administered for 11 weeks under ad libitum and restrictive feeding conditions to 48 pigs of both sexes, which were randomly divided into four groups (n = 12 per group). Feed intake was 2.90 kg/day, live weight gain 987 g/day and feed to gain ratio 2.77 kg/kg for the ad libitum fed control group. The group fed DON contaminated wheat ad libitum significantly consumed 15% less feed and gained 13% less live weight, while the feed to gain ratio was unaffected. Moreover, it was concluded that the lower growth performance by DON contaminated feed resulted mainly from the lower voluntary feed intake, because there were no differences in live weight gain between the groups with the restrictive feeding regimen. On the contrary, metabolizable energy, nitrogen retention digestibility of organic matter, crude protein, crude fat and crude fibre were significantly increased by 3, 10, 3, 6, 9 and 20% in the DON group respectively. Animals fed DON contaminated diets needed more time to consume the restrictive ration than the control group. For example in the first hour after feeding 85% of the control pigs had consumed all feed, but only 39% of the DON group had. There were only few differences in haematological and serum parameters, which were characterized by a high variation between individuals. DON and IgA concentrations in serum were significantly influenced by DON exposure.


Identification and typing of miso and soy sauce fermentation yeasts, Candida etchellsii and C. versatilis, based on sequence analyses of the D1D2 domain of the 26S ribosomal RNA gene, and the region of internal transcribed spacer 1, 5.8S ribosomal RNA gene and internal transcribed spacer 2.
We analyzed sequences of the D1D2 domain of the 26S ribosomal RNA gene (26S rDNA sequence), and the region of internal transcribed spacer 1, 5.8S ribosomal RNA gene and internal transcribed spacer 2 (ITS sequence) of the miso and soy sauce fermentation yeasts, Candida etchellsii and Candida versatilis, in order to evaluate the usefulness of this sequence analysis for identification and typing of these two species. In the 26S rDNA sequence method, the numbers of base substitutions among C. etchellsii strains were up to 2 in 482 bp (99.6% similarity), and they were divided into three types (types A, B, and C). Those of C. versatilis strains were also up to 2 in 521 bp (99.6% similarity) and they were divided into three types (types 1, 2, and 3). In the ITS sequence method, those of C. etchellsii strains were zero in 433 bp (type a, 100% similarity). Those of C. versatilis were 5 in 409 bp (98.8% similarity), divided into 4 types (types I, II, III and IV). It was found that molecular methods based on the sequences of the 26S rDNA D1D2 domain and the ITS region were rapid and precise compared with the physiological method for the identification and typing of these two species.


[Atypical presentation of intra-abdominal extralobar pulmonary sequestration detected in prenatal care: a case report].
To describe an unusual clinical presentation of intra-abdominal extralobar pulmonary sequestration in a 2-year, 9 month-old patient and assess diagnostic and treatment aspects of this pathology. An undefined intra-abdominal mass was identified in the right adrenal region in a male fetus. Postnatal evaluation with ultrasound images, computed tomography, magnetic resonance imaging and laboratory testing was insufficient to determine the nature of the lesion. After two years, laparoscopic resection of the mass and histopathological examination of the surgical specimen allowed to establish the diagnosis of intra-abdominal extralobar pulmonary sequestration. This malformation can be monitored clinically; however, surgical excision is often performed, probably due to the impossibility of attaining diagnosis with non-invasive methods, such as in the present case, in which the lesion appeared in an unusual position for intra-abdominal extralobar pulmonary sequestration. Therefore, the surgical approach seems to be the key to attain the diagnosis and establish the conduct for this type of congenital malformation.


A Case of Concurrent Acute Macular Neuroretinopathy and Paracentral Acute Middle Maculopathy Following Pfizer-BioNTech COVID-19 Vaccination.
We present a 65-year-old woman who developed sudden and severe vision loss in her left eye one day after the administration of the second dose of COVID vaccine. The best corrected visual acuity in this eye was 1/10. Diffuse paracentral acute middle maculopathy was detected on spectral domain optical coherence tomography (OCT). OCT angiography images revealed concurrent vascular flow defects consistent with acute macular neuroretinopathy in the deep retinal capillary plexus and choriocapillaris layers. At the end of the six-month follow-up, there was no improvement in visual acuity, and atrophy and thinning developed in all layers of the retina.


Analysis of Rapidly Mutating Y Chromosome Short Tandem Repeats (RM Y-STRs).
Rapidly mutating (RM) Y-STRs were recently identified and can help to differentiate between paternally related males in paternity and forensic casework. Normal Y-STRs are often used in casework due to their paternal inheritance, which can help to resolve kinship cases, and identify male components in male/female mixtures; however, more discriminating profiles are obtained if rapidly mutating Y-STRs are used. Previously two or three multiplex PCRs have been used to amplify 13 RM Y-STRs; here, an assay amplifying these 13 markers in a single multiplex PCR is described. Commercially available male control DNA samples have been genotyped during the validation of this assay, thus providing a tool for calibrating genotyping results. It is expected that the assay will provide a niche tool for genotyping casework samples.


[Fishtail deformity after a non-displaced supracondylar humeral fracture in childhood: A case report].
We report the case of a 13-year-old boy presenting with stiffness and pain in the elbow, which had appeared a few years before consultation. He reported a history of a closed, nondisplaced supracondylar fracture of the humerus 7 years before. Progression was good after orthopedic treatment. X-rays and CT showed a distinctive deformation, called a fishtail deformity, associated with severe arthritic injuries. We recall here that supracondylar fractures of the humerus are common in children and that early reduction decreases the complication rate. However, this case shows that fishtail deformity is a late and serious complication, which may occur after a nondisplaced supracondylar fracture of the humerus, with no severity factors and with good early progression.


Durability improvement of polymer chamber of pulsatile extracorporeal life support system in terms of mechanical change.
Twin Pulse Life Support, T-PLS has received the CE mark (2003) and Korea Food and Drug Administration (KFDA) approval (2004) for short-term application as an Extracorporeal Life Support system (ECLS). T-PLS's original intention was to apply for not only short-term but also long-term application such as Extracorporeal ventricular assist device (VAD). Hence, a long-term durability test was conducted. The 1-year reliability of the systems tested in this study did not meet the STS/ASAIO standard of 80% reliability with 60% confidence for a 1-year mission life. However, without the disposable units, which are only designed to operate for 6 h, the 1-year reliability exceeded the STS/ASAIO standard of 80% reliability with 60% confidence. In this study, by using the existing analysis methods and analyzing the root cause of the failure used by a numerical analysis. As eliminating or mitigating of the root cause of the failure, we improved the durability of blood chamber and evaluated the performance of the modified system via the hemolysis test.


Local control after craniospinal irradiation, intensity-modulated radiotherapy boost, and chemotherapy in childhood medulloblastoma.
The current study was conducted to determine whether the use of cochlear-sparing intensity-modulated radiotherapy (IMRT) boost results in excess local failures in children with medulloblastoma. Fifty children with a median age of 7.8 years underwent resection, craniospinal irradiation (CSI), IMRT posterior fossa (PF) and/or tumor bed (TB) boost, and cisplatin-based chemotherapy for medulloblastoma. For standard-risk patients, the CSI dose was 18 to 23.4 grays (Gy) and was followed either by an IMRT PF boost to 36 Gy and a TB boost of 54 to 55.8 Gy (n = 29) or by an IMRT TB boost to 55.8 Gy (n = 4). For high-risk patients, the CSI dose was 36 to 39.6 Gy followed by an IMRT PF boost to 54 to 55.8 Gy (n = 8), an IMRT PF boost to 45 Gy and a TB boost to 55.8 Gy (n = 2), or an IMRT TB boost to 55.8 Gy (n = 7). For the TB boost, a 2-cm margin around the surgical bed was treated in most patients. The 5-year overall and progression-free survival rates (±standard deviation) were 72% ± 6.6% and 68.3% ± 6.8%, respectively, for all patients; 77.8% ± 7.4% and 75.1% ± 7.6%, respectively, for standard-risk patients; and 60.8% ± 12.8% and 55.4% ± 12.8%, respectively, for high-risk patients. The 5-year PF control rate was 90.5% ± 4.6%. TB failures occurred in 3 patients (including 2 patients who had distant failure), whereas an isolated non-TB PF failure occurred in 1 patient. The use of IMRT was associated with excellent local control and did not result in excess PF failures outside of the TB.


Metabolism of americium-241 in man: an unusual case of internal contamination of a child and his father.
The metabolism of americium-241 has been studied during an 8-year period in an adult male and his son who, at the ages of 50 and 4 years, respectively, were accidentally and unknowingly contaminated within their home by means of inhalation. Chelation therapy with calcium trisodium pentetate was more effective in enhancing the removal of americium-241 from the child than from the father.


The Influence of Finasteride on Mean and Relative Spectral Density of EEG Bands in Rat Model of Thioacetamide-Induced Hepatic Encephalopathy.
Liver failure is associated with a neuropsychiatric syndrome, known as hepatic encephalopathy (HE). Finasteride, inhibitor of neurosteroid synthesis, may improve the course of HE. The aim of our study was to investigate the influence of finasteride on mean and relative power density of EEG bands, determined by spectral analysis, in rat model of thioacetamide-induced HE. Male Wistar rats were divided into groups: (1) control; (2) thioacetamide-treated group, TAA (900 mg/kg); (3) finasteride-treated group, FIN (150 mg/kg); and (4) group treated with finasteride (150 mg/kg) and thioacetamide (900 mg/kg), FIN + TAA. Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered during 3 subsequent days, and in FIN + TAA group FIN was administered 2 h before every dose of TAA. EEG was recorded 22-24 h after treatment and analyzed by fast Fourier transformation. While TAA did not induce significant changes in the beta band, mean and relative power in this band were significantly higher in FIN + TAA versus control group (p < 0.01). TAA caused a significant decline in mean power in alpha, theta, and delta band, and in FIN + TAA group the mean power in these bands was significantly higher compared with control. While in TAA group relative power was significantly decreased in theta (p < 0.01) and increased in delta band (p < 0.01) versus control, the opposite changes were found in FIN + TAA group: an increase in theta (p < 0.01) and a decrease in delta relative power (p < 0.01). In this study, finasteride pretreatment caused EEG changes that correspond to mild TAA-induced HE.


Effects of orally administered OP-1206 alpha-CD with loxoprofen-Na on walking dysfunction in the rat neuropathic intermittent claudication model.
An orally active prostaglandin E1 analogue, OP-1206 alpha-CD improves walking dysfunction in the rat spinal stenosis model. Loxoprofen-Na, a non-steroidal anti-inflammatory drug, is used to relieve chronic pain in patients with lumbar spinal canal stenosis. To determine whether the OP-1206 alpha-CD in combination with loxoprofen-Na could induce a greater therapeutical effect on walking dysfunction and spinal cord blood flow (SCBF) than OP-1206 alpha-CD treatment alone after chronic spinal stenosis in the rat. Spinal stenosis was induced by placing two pieces of silicon rubber strips in the lumbar (L4 and L6) epidural space of rats. After surgery, walking function was measured using a treadmill apparatus and SCBF was measured using a laser-Doppler flow meter. Drugs were administered orally twice a day for 11 days from the day 3 post-surgery. OP-1206 alpha-CD elicited a significant improvement of walking dysfunction on days 7 and 14 post-surgery and significantly increased spinal cord blood flow on day 15, whereas walking dysfunction and SCBF of rats treated with loxoprofen-Na alone remained unchanged. Combined treatment of OP-1206 alpha-CD with loxoprofen-Na did not provide additive therapeutical effect. These results suggest that a significant improvement seen after OP-1206 alpha-CD treatment is primarily mediated by improvement of the local spinal cord blood flow. This effect is not ameliorated or potentiated by a combined treatment with loxoprofen-Na.


An improved method for the synthesis of zirconium (CCC-N-heterocyclic carbene) pincer complexes and applications in hydroamination.
Upon heating Zr(NMe(2))(4), 1,3-bis(N-butyl-imidazolium)benzene diiodide and toluene analytically pure Zr pincer complex was obtained, which was found to be an intramolecular hydroamination catalyst.


Structural characterization of BPI-modulating 15 kDa proteins from rabbit polymorphonuclear leukocytes: identification of a novel family of leukocyte proteins.
We have previously described the isolation and initial characterization of 15 kDa protein isoforms (p15s) from rabbit polymorphonuclear leukocytes (PMN) that bind to Escherichia coli and modulate the antibacterial actions of other leukocyte proteins on this gram negative organism. We now report that the p15s differ in primary structure. The cloning and sequencing of two distinct p15 cDNAs from a rabbit bone marrow library reveal that two of the isoforms are closely similar in primary structure differing at only two amino acid positions. The p15 cDNAs encode putative signal sequences suggesting a granule-associated localization for these proteins. Analysis of the derived p15 primary structures reveals homology to two leukocyte proteins: CAP-18, an 18 kD lipopolysaccharide (LPS) binding protein from rabbit PMN and cathelin, an 11 kD cysteine protease inhibitor from porcine leukocytes. This structural similarity suggests the existence of a novel family of low molecular weight leukocyte proteins with potential roles in inflammation.


Dermatologic photography.
Particularly for the beginning clinical photographer, the details of contour light, texture light, flat light, and fill lights may be intimidating. A physician-photographer may elect to choose a name brand system that has manual exposure capability. The system should include a ring light (or ring light equivalent) and a point source with a guide number of at least 80 (feet with ISO 100 film). Standard exposures may be determined, as has been described above. The ring light should be used for reproduction ratios between 1:1 and 1:20; the point source is saved for ratios of 1:20 and below. As confidence and skill increase, the photographer may choose to use additional light sources, facilitating more subtle forms of lighting. Criteria for choosing equipment have been examined in great detail. The importance of using standardized manual strobe lighting at set reproduction ratios as opposed to automated systems using through the lens flash metering has been stressed. Flat, contour, and texture lighting with techniques to decrease shadow density was also addressed at length. Standard views of body areas, lesion photography, and image storage methods were discussed as well.


Flattening generalization gradients, context, and perceptual learning.
The present research investigated the effects of physical context change and perceptual learning on generalization. In a video game, participants learned to suppress their mouse-clicking behavior in the presence of one stimulus (AX). Generalization was observed between the AX stimulus and another stimulus (BX) that was designed to be similar. When testing was conducted in a context different from that in which AX was used in training, responding to AX was attenuated, and responding to BX was enhanced. That is, the generalization gradient flattened. The latter effect was only evident in groups for which generalization had been reduced through a preexposure manipulation believed to produce perceptual learning. Experiment 2 demonstrated that the increase in generalization observed in the first experiment was due to the context change between the preexposure and test rather than to a change between the conditioning and test contexts. Implications for flattening generalization gradients and mechanisms of perceptual learning are discussed.


Evaluation of anterior oblique ligament tension at the elbow joint angle-a cadaver study.
The ulnar collateral ligament complex, particularly the anterior oblique ligament (AOL), is mainly a static stabilizer controlling valgus. Various studies have been conducted on the kinematics of elbow joints after ligament cutting; however, no biomechanical studies have measured the tension applied to the ligament. Finite element modeling (FEM) is a very useful tool for biomechanical evaluation of the elbow. However, an accurate FEM of elbow joints cannot be developed without information on the potential tension of ligaments applied during the flexion and extension of elbow joints. We believe that FEM of the elbow joint could be obtained by measuring the material properties and potential tension of the ligament applied during the flexion and extension of the elbow joint. This study aimed to measure the potential tension and material properties of the ligament during the flexion and extension of the elbow, by identifying the relation between ligament length and tension using mechanical testing. We included 10 elbows harvested from 7 fresh-frozen cadavers. The average age of the cadavers was 83.7 ± 5.65 years, and the samples included 8 elbows from 6 male cadavers and 2 elbows from 1 female cadaver. We measured the ligament length at each elbow angle by changing the elbow joint from 0° to 120° in 15° intervals. Thereafter, we extracted the AOL and divided into an anterior band (AB) and a posterior band (PB) and performed a mechanical test to calculate ligament stress. The ligament length of the AB gradually decreased as the flexion angle increased. Conversely, the ligament length of the PB gradually increased as the flexion angle increased. AB and PB lengths were approximately the same between 60° and 75°. The average ligament tension and stress of the AB gradually increased with elbow extension. In contrast, the average ligament tension and stress of the PB gradually increased with elbow flexion. The tension and stress of the AB and PB were balanced around the elbow joint at 60°. The AB was tenser on elbow extension, and the PB was tenser following elbow flexion. Also, the angle at which the AOL stress was equalized was 60°, suggesting that ∼60° is the angle at which the AOL is unlikely to be damaged.


Canine leishmaniasis in Southern Italy: a role for nitric oxide released from activated macrophages in asymptomatic infection?
Human and canine leishmaniasis (CanL) by Leishmania infantum is endemic in Italy, with a high percentage of infected asymptomatic animals. However, the immune response mechanisms underlying the clinical presentation of CanL have not been fully investigated. Among leishmanicidal molecules produced by activated macrophages, nitric oxide (NO) produced by an inducible NO synthase seems to play an important protective role, but no conclusive data are available. Therefore, NO released by cultured macrophages from dogs with natural Leishmania infection living in an endemic area for CanL was evaluated. On the basis of one year's clinical and laboratory follow-up, 22 dogs infected by Leishmania infantum were identified and grouped as: asymptomatic dogs (n = 13) and dogs with symptoms of leishmaniasis (n = 9). Each animal was bled twice at 4-month intervals and macrophage and lymphocyte cultures were obtained from peripheral blood mononuclear cells. Supernatants of L. infantum-infected macrophage cultures, with or without addition of autologous lymphocytes, were assayed for NO production by Griess reaction for nitrites. In the first months of the infection the levels of NO in supernatants of Leishmania-infected macrophages were higher in symptomatic than in asymptomatic dogs, but they were significantly increased in the latter group eight months after the diagnosis of infection. Furthermore, NO release significantly decreased in the presence of autologous lymphocytes in both groups of animals. These results suggest that NO may be involved in the long-term protection of dogs against natural Leishmania infection and in the clinical presentation of canine leishmaniasis in the Mediterranean area.


Clinical Effects of a Home Care Pilot Program for Patients with Type 1 Diabetes Mellitus: A Retrospective Cohort Study.
Given the importance of continuous self-care for people with type 1 diabetes mellitus (T1DM), the Ministry of Health and Welfare of Korea launched a pilot program for chronic disease management. Herein, we applied a home care pilot program to people with T1DM to investigate its effects. This retrospective cohort study was conducted at a single tertiary hospital (January 2019 to October 2021). A multidisciplinary team comprising doctors, nurses, and clinical nutritionists provided specialized education and periodically assessed patients' health status through phone calls or text messages. A linear mixed model adjusting for age, sex, and body mass index was used to analyze the glycemic control changes before and after implementing the program between the intervention and control groups. Among 408 people with T1DM, 196 were enrolled in the intervention group and 212 in the control group. The reduction in glycosylated hemoglobin (HbA1c) after the program was significantly greater in the intervention group than in the control group (estimated marginal mean, -0.57% vs. -0.23%, P=0.008); the same trend was confirmed for glycoalbumin (GA) (-3.2% vs. -0.39%, P<0.001). More patients achieved the target values of HbA1c (<7.0%) and GA (<20%) in the intervention group than in the control group at the 9-month follow-up (34.5% vs. 19.6% and 46.7% vs. 28.0%, respectively). The home care program for T1DM was clinically effective in improving glycemic control and may provide an efficient care option for people with T1DM, and positive outcomes are expected to expand the program to include more patients.


Processing of prodynorphin by the prohormone convertase PC1 results in high molecular weight intermediate forms. Cleavage at a single arginine residue.
Processing of rat prodynorphin (proDyn) by the mouse prohormone convertase PC1 was investigated. Recombinant vaccinia virus vectors were used to coexpress proDyn and PC1 in rat PC12 pheochromocytoma and mouse AtT-20 corticotroph cells. In vitro experiments were also conducted by co-incubating purified proDyn and PC1. The results demonstrate that PC1 cleaves proDyn at pairs of basic residues to yield 10 and 16 kDa high molecular weight (HMW) intermediates. Additionally, PC1 cleaves proDyn at a single arginine residue to yield an 8 kDa product and the C-peptide. This demonstrates that PC1 cleaves proDyn at single and pairs of basic residues.


Physical Activity, Coronary Artery Calcium, and Cardiovascular Outcomes in the Multi-Ethnic Study of Atherosclerosis (MESA).
Although the inverse relationship between physical activity (PA) and cardiovascular disease (CVD) is well established, observational studies suggest that very high levels of PA may be harmful. This study sought to understand the relationship between PA, coronary artery calcium (CAC), and cardiovascular outcomes among individuals at different levels of risk. PA and CAC were assessed in 6777 baseline participants of the Multi-Ethnic Study of Atherosclerosis. Total PA in MET-minutes per week was categorized into quartiles, and CAC was categorized as "low risk" (<100 Agatston units; n = 5180) and "high risk" (≥100 Agatston units; n = 1597). Cox proportional hazard regression analyses and Kaplan-Meier curves were generated to understand relationships between PA and CAC with CVD and all-cause mortality. In low-risk participants in the highest PA quartile, there was a decrease in the adjusted hazard ratio (HR) for CVD (HR, 0.72; 95% confidence interval (CI), 0.56-0.94) and all-cause mortality (HR, 0.69; 95% CI, 0.57-0.84) compared with those in the lowest PA quartile. In high-risk participants in the highest PA quartile, there was a decrease in the adjusted HR for all-cause mortality (HR, 0.59; 95% CI, 0.47-0.74) compared with those in the lowest PA quartile. High PA was not associated with an increased risk of either outcome, regardless of CAC category, sex, or race/ethnicity. Our research suggests that there is no increased risk associated with high levels of PA, even among individuals at high risk of CVD.


Robust polystyrene resin-supported nano-CoFe2O4 mediated peroxymonosulfate activation for efficient oxidation of 1-hydroxyethane 1,1-diphosphonic acid.
Nanosized spinel cobalt ferrite (CoFe2O4) shows high performance in peroxymonosulfate (PMS) activation for decontamination in water, but is yet challenged by the easily leached Co(II) with high toxicity. Herein, macroporous polystyrene resin is used as the support to improve the stability of CoFe2O4 nanoparticles during PMS activation. CoFe2O4@S201 exerted high catalytic activity toward PMS activation for oxidation of 1-hydroxyethane 1,1-diphosphonic acid (HEDP), with the apparent rate normalized by Co content 38.2 times higher than that of the unsupported CoFe2O4. Meanwhile, one order of magnitude lower Co leaching (< 2.1 μg L-1) was detected during the catalytic oxidation. The Co(II)-PMS complex was the primary oxidant responsible for the oxidation of HEDP. The catalytic durability and stability of CoFe2O4@S201 for degradation of HEDP in actual wastewater were systematically evaluated in both batch and continuous-flow mode. It is found that the organic resin, which is often considered to be intolerant to oxidation, is rather stable during the non-radical process. The total cobalt leaching of the fresh CoFe2O4@S201 cannot be ignored in the 100-h continuous-flow run. In contrast, much lower cobalt leaching and slightly higher oxidation efficiency were observed for the regenerated CoFe2O4@S201, which might be due to the removal of unreactive and unstable Co sites on the surface in the first trial. The findings shed light on the potential of organic supports for improving the stability and activity of nanosized CoFe2O4 and other nano-catalysts toward practical application.


Chemical characterization and safety assessment of dokha: An emerging alternative tobacco product.
Dokha is known to be one of the most rapidly spreading alternative tobacco products (ATPs) in the Middle East and North Africa (MENA) region. It is smoked using a pipe known as Midwakh. There is no scientific research published on the chemical composition of dokha and only very little was done to investigate its impact on human health. Three different types of dokha were included in this study. The trace metals content in the dokha samples were analyzed using inductively-coupled plasma-optical emission spectroscopy and energy-dispersive X-ray spectroscopy-scanning electron microscope. Dokha smoke was generated using a device that simulates human smoking/puffing. The smoke samples were collected on Tenax and activated carbon adsorbent tubes followed by chemical analysis using thermal desorption-gas chromatography-mass spectrometry. The results showed the presence of toxic metals in dokha samples such as cobalt, cadmium, chromium, and lead in amounts classified as harmful to human health. In addition, the presence of several potentially harmful and even toxic organic compounds in dokha smoke was identified based on the available clinical data. These included 22 irritants, 3 known carcinogens, and 5 central nervous system (CNS) depressants in addition to several other compounds with miscellaneous effects. The findings of this work demonstrate evidence for the presence of potentially harmful and toxic metals and compounds in dokha tobacco as well as dokha smoke. More research is required to further investigate the clinical impact of dokha on human health.


Dual-head gamma camera coincidence imaging in pancreatic cancer.
To assess the usefulness of dual-head camera imaging with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in the identification of malignant pancreatic lesions. Fifteen (15) patients with pancreatic masses (7 females and 8 males, mean age 52 10 years) have been studied prospectively. After a 12-hour fasting patients received 120 MBq of FDG and were imaged in a dual-head camera equipped with coincidence detection. The final diagnosis was obtained by histology (biopsy or surgery in 13 patients) or follow-up (in 2 patients). Nine patients showed FDG uptake, all had pancreatic cancer proven on histological examination. Six patients had no tracer uptake: two had chronic pancreatitis, 1 had insulinoma, 1 had gastrinoma and two had pancreatic adenocarcinoma. Overall sensitivity was 69%, specificity was 100% and accuracy was 73%. Dual-head camera FDG images seem potentially useful in the characterization of the nature of pancreatic lesions. However, a negative study does not rule out malignancy in this patient population.


Assessment of the risk factors for intraoperative pressure injuries in patients.
This study was conducted to assess the risk factors for pressure injuries in patients during surgery. In this descriptive cross-sectional study, the risk of pressure injuries during surgery was evaluated in 250 patients in a university hospital. Data were collected through a Patient Descriptive Information Form (PDIF) and the 3S Intraoperative Pressure Injury Risk Assessment Scale (IPIRAS). The mean age of the patients was 44.15 ± 17.00, and 52.4% were female. In addition, it was determined that the mean 3S IPIRAS score was higher in patients who were male, were aged ≥60 years, were obese, had a chronic disease, and had low serum albumin and hemoglobin levels (p < .05). During the surgery of the patients included in the study, support surfaces were used in 67.6%, positioning aids were used in 82.4%, and 55.6% had normal skin. Patients who underwent CVS procedures for more than 6 h, did not use support surfaces during surgery, had moist skin, or used vasopressors had higher and significantly different mean 3S IPIRAS scores (p < .05). According to the results, all surgical patients were at risk for pressure injury in the intraoperative period. In addition, it was found that male gender was associated with risk factors and that being aged ≥60 years, obesity, chronic disease, low serum hemoglobin and albumin levels, CVS, operations lasting more than 6 h, moist skin, vasopressor drugs, and not using support surfaces during surgery increased the risk of pressure injuries significantly.


A systematic approach for discovering novel, clinically relevant bacteria.
Sequencing of the 16S rRNA gene (16S) is a reference method for bacterial identification. Its expanded use has led to increased recognition of novel bacterial species. In most clinical laboratories, novel species are infrequently encountered, and their pathogenic potential is often difficult to assess. We reviewed partial 16S sequences from >26,000 clinical isolates, analyzed during February 2006-June 2010, and identified 673 that have <99% sequence identity with valid reference sequences and are thus possibly novel species. Of these 673 isolates, 111 may represent novel genera (<95% identity). Isolates from 95 novel taxa were recovered from multiple patients, indicating possible clinical relevance. Most repeatedly encountered novel taxa belonged to the genera Nocardia (14 novel taxa, 42 isolates) and Actinomyces (12 novel taxa, 52 isolates). This systematic approach for recognition of novel species with potential diagnostic or therapeutic relevance provides a basis for epidemiologic surveys and improvement of sequence databases and may lead to identification of new clinical entities.


Short-term outcome after computer-assisted versus conventional total knee arthroplasty: a randomised controlled trial.
To compare the short-term functional outcome after computer-assisted total knee arthroplasty (TKA) versus conventional TKA. 23 men and 67 women aged 48 to 80 years were randomised to undergo (1) conventional TKA using an intramedullary guide, (2) conventional TKA using an extramedullary guide, or (3) computer-assisted TKA. Two senior surgeons performed all the TKAs using the same TKA system and the standard anteromedial arthrotomy with eversion of the patella. Patients were assessed by physiotherapists before and 6 months and 2 years after TKA using the Short Form-36 Health Survey, Oxford Knee Score, and Knee Society Score. Of the 90 patients, 67 and 70 were assessed at 6 months and 2 years after TKA, respectively. No patient developed deep infection or required revision surgery. Functional outcomes of the 3 groups did not differ significantly at the corresponding follow-ups. Significant improvement in the functional outcome was not shown in patients treated with computer-assisted TKA, compared with conventional TKA. Thus, computer-assisted TKA has limited additional short-term benefits. Further studies with longer follow-up are required to examine the benefits of computer-assisted TKA.


A comparison of two approaches to extracting Cryptosporidium DNA from human stools as measured by a real-time PCR assay.
Direct extraction of Cryptosporidium DNA from 46 stools by bead-beating, guanidine thiocyanate and silica purification provided slightly lower PCR positivity (93.5% vs. 100%) and higher threshold cycle values (mean 34.93 vs. 28.03; P=0.00) than spin-column extraction from boiled, semi-purified oocyst suspensions. However, direct extraction is cheaper, and amenable to automation.


Effect of exogenous surfactant on phosphatidylinositol 3-kinase-Akt pathway and peroxisome proliferator activated receptor-γ during endotoxin induced acute respiratory distress syndrome.
Lipopolysaccharide induced acute respiratory distress syndrome (ARDS) leads to an unacceptably high mortality. In this regard, the anti-inflammatory properties of surfactant may provide a therapeutic option. Phosphoinositide 3-kinase (PI3-K) and the downstream serine/threonine kinase Akt/protein kinase B have a central role in modulating neutrophil function, including respiratory burst, chemotaxis, and apoptosis. This study explores the mechanisms of surfactant dependent protection by regulating PPAR-γ in a rat model of ARDS. Sprague-Dawley male rats were divided into four groups: buffer controls; rats challenged with LPS (055:B5 E. coli); challenged with LPS and treated with porcine surfactant; and challenged with LPS and treated with synthetic surfactant. Expression of PI3-K, Akt, GSK3-β, and PPAR-γ were studied by western immunoblot, immunofluorescence and by immunohistochemistry. In vivo endotoxin administration to rat resulted in activation of PI3-K and Akt in the lungs. The severity of endotoxemia-induced ALI was significantly diminished in rat with surfactant administration. Similar results were also seen in PPAR-γ expression. These results show that PI3-K occupies a central position in regulating endotoxin-induced ALI involving inflammatory responses. Surfactant treatment conferred protection in rat model dependent on PPAR-γ and inhibition of PI3-K/Akt pathway.


Mutagenicity of potentially carcinogenic mycotoxins produced byFusarium moniliforme.
The mutagenic behaviour of two potentially carcinogenic mycotoxins produced byFusarium moniliforme was investigated in theSalmonella mutagenicity test using tester strains TA97a, TA98, TA100, and TA102. The mutagenic response obtained with fusarin C (1, 5, and 10μg/plate) against tester strains TA98 and TA100 in the presence of microsomal activation confirmed previous observations on the mutagenic behaviour of this mutagen while that obtained against TA97a is reported for the first time. No dose-response relationship could be detected for the concentration levels (0.2, 0.5, 1, 5, 10 mg/plate) tested for FB1, FB2, and FB3 against any of the tester strains used in either the plate incorporation and / or the pre-incubation tests. A cytotoxic effect was obtained at concentration levels of 5 and 10mg/plate in the absence of the microsomal activation mixture. From the studies it became evident thatF moniliforme produces two compounds, a mutagenic compound, fusarin C which has been shown to lack carcinogenic activity in rats and the non-mutagenic fumonisin B mycotoxins of which FB1 is known to be responsible for the hepatocarcinogenicity of the fungus in rats.


Functional characterization of the CC chemokine RANTES from Pekin duck (Anas platyrhynchos).
RANTES (Regulated upon Activation, Normal T-cell Expressed and Secreted) is a key pro-inflammatory cytokine that belongs to the CC-group of chemokines. The present study was carried out to functionally characterize the previously identified RANTES homologue in domestic duck (GenBank Accession No. AY641435). Recombinant duck RANTES was expressed in Escherichia coli-based and HEK293T cell-based systems. A tRNA supplementation strategy was required to express the protein in E. coli due to the presence of rare codons. In biological assays using HEK293T cell-expressed protein, RANTES was found to mediate chemotaxis of DT-40 chicken B cells and primary duck splenocytes at a concentration of 0.505μg/ml (0.6μM). Immunostaining of the migrated splenocytes using anti-duck CD4 and CD8 monoclonal antibodies and subsequent flow cytometric analysis showed enhanced chemotaxis of CD8+ cells. The recombinant RANTES exhibited in vitro antiviral activity by inhibiting infection of chicken embryo fibroblast cells with duck enteritis virus (DEV) at the same concentration. The effect could be neutralized by rabbit anti-duck RANTES polyclonal serum. The mechanism seems to be direct on viral particles as evidenced by the need for co-incubation of RANTES with DEV prior to the infection for antiviral activity, and also by the enhanced binding of DEV to E. coli expressed purified RANTES on ELISA-based assays. Our results show that the duck RANTES has overlapping biological properties with its mammalian orthologue, and also has possible functional cross-reactivity with chicken immune cells indicated by the chemotaxis of DT-40 cells.


Lack of interaction between metoclopramide and morphine in vitro and in mice.
1. This study examined interactions via common metabolism or via common pharmacodynamic pathways between frequently co-prescribed metoclopramide (a prokinetic) and morphine (an opioid analgesic). 2. In human liver microsomes, morphine 3-glucuronide and morphine 6-glucuronide formation had V(max) estimates of 6.2 +/- 0.07 and 0.75 +/- 0.01 (nmole min(-1) mg(-1) protein) and K(m) estimates of 1080 +/- 37 and 665 +/- 55 (microM), respectively. The in vitro K(i) for morphine 3-glucuronide formation in the presence of metoclopramide in human liver microsomes or recombinant uridine diphosphoglucuronosyltransferase 2B7 predicted a lack of in vivo interaction. 3. Morphine (2 mg kg(-1) subcutaneously) delayed gastrointestinal meal transit in mice, metoclopramide (10 mg kg(-1) subcutaneously) had no effect on meal transit, and metoclopramide did not alter this effect of morphine. 4. Morphine (2 or 5 mg kg(-1) subcutaneously) was antinociceptive in mice (hot plate test) and metoclopramide (10 mg kg(-1) subcutaneously) did not alter the antinociceptive effects of morphine. 5. Together, the data suggest a lack of interaction between morphine and metoclopramide.


Sorbitol catharsis does not enhance efficacy of charcoal in a simulated acetaminophen overdose.
The use of a 70% sorbitol solution has recently been advocated as an adjunct to activated charcoal. This results in rapid and profuse catharsis that could possibly cause fluid and electrolyte imbalance. An investigation was undertaken to determine if sorbitol catharsis enhanced the antidotal efficacy of activated charcoal. Eight healthy volunteers participated in a randomized, crossover trial. Subjects ingested 3 g of acetaminophen followed by either no intervention, 50 g of plain activated charcoal at one hour, or 50 g activated charcoal-sorbitol solution at one hour. Serial acetaminophen levels were determined at intervals over eight hours and side effects noted. Both interventions significantly reduced the area under the curve versus control (P less than .05). The addition of sorbitol did not enhance the efficacy of activated charcoal but did increase the side effects noted. Sorbitol has not been proven effective in enhancing drug removal and has side effects that can be significant in a poisoned patient. Current data do not warrant its use, and further investigations should be carried out with other ingested drugs.


"Technological" approach versus clamp crushing technique for hepatic parenchymal transection: a comparative study.
We evaluated the feasibility and effectiveness of combining two different electronic devices, the ultrasonic dissector (UD) and the harmonic scalpel (HS), during hepatic resection. One hundred consecutive patients underwent liver resection using UD plus HS between January and December 2004 (UD + HS group). The ultrasonic dissector was used to fracture liver parenchyma and the uncovered vessel was sealed using the HS. Surgical outcomes were compared with 100 consecutive patients who underwent liver resection using the clamp crushing method. Operative variables, postoperative liver function, hospital stay, and type and number of complications were compared. The two groups were equivalent in term of demographic and pathologic variables. The UD + HS group had a decreased blood loss (500 ml versus 700 ml, P = 0.005), number of patients transfused (22 versus 39, P = 0.009), tumor exposure at the transection surface (4 versus 12, P = 00.012), and hospital stay (7 versus 8.5 days, P = 0.020). Postoperative major complications, in particular, fluid collection and biliary fistula, were significantly less frequent in the UD + HS group (2 versus 9, P = 0.030). A longer operative time was recorded in the UD + HS group (385 versus 330 minutes, P = 0.001). The combined use of UD with HS allows liver resection to be safely performed, with the advantage of reducing blood losses and surgery-related complications. The only major disadvantage may be a longer transection time.


Alterations of intracranial pressure and cerebral blood flow velocity in healthy neonates and their implication in the origin of perinatal brain damage.
Intracranial pressure and cerebral blood flow velocity were recorded in term healthy neonates during the first 3 days of life using non-invasive methods (LADD-fontanometry and cw-Doppler sonography). Intracranial pressure increased from 4.0 +/- 2.7 cm H2O to 5.8 +/- 2.7 cm H2O and maximal cerebral blood flow velocity in the anterior cerebral artery (ACA) increased from 33 cm/s to 58 cm/s as calculated from a Doppler shift of 0.63 to 1.10 kHz and vascular resistance decreased between the 1st and 3rd day of life. These alterations could not be demonstrated in the femoral artery. This is in accordance with other registrations obtained by different methods and under various conditions. They allow an explanation of some well known physiological phenomena like alterations of cranial volume and the structure of the bony skull in the first days of life. Furthermore, these physiological variations may have implications for the origin of cerebral damage during the perinatal period, especially of hypoxic-ischaemic encephalopathies.


Prevalence of depression and anxiety symptoms in elderly patients admitted in post-acute intermediate care.
Depression and anxiety symptoms are common in medically ill older patients. We investigated the prevalence and predictors of depression and anxiety symptoms in older patients admitted for further rehabilitation in post acute intermediate care. Observational cohort study. An intermediate care unit, North West of England. One hundred and seventy-three older patients (60 male), aged mean (SD) 80 (8.1) years, referred for further rehabilitation to intermediate care. Depression and anxiety symptoms were assessed by the Hospital Anxiety and Depression Scale, and severity of depression examined by the Montgomery Asberg Depression Rating Scale. Physical disability was assessed by the Nottingham Extended ADL Scale and quality of life by the SF-36. Sixty-five patients (38%) were identified with depressive symptoms, 29 (17%) with clinical depression, 73 (43%) with anxiety symptoms, and 43 (25%) with clinical anxiety. 15 (35%) of the latter did not have elevated depression scores (9% of the sample). Of those with clinical depression, 14 (48%) were mildly depressed and 15 (52%) moderately depressed. Longer stay in the unit was predicted by severity of depression, physical disability, low cognition and living alone (total adjusted R2 = 0.24). Clinical depression and anxiety are common in older patients admitted in intermediate care. Anxiety is often but not invariably secondary to depression and both should be screened for. Depression is an important modifiable factor affecting length of stay. The benefits of structured management programmes for anxiety and depression in patients admitted in intermediate care are worthy of evaluation.


A review of the state-of-the-art in automatic post-editing.
This article presents a review of the evolution of automatic post-editing, a term that describes methods to improve the output of machine translation systems, based on knowledge extracted from datasets that include post-edited content. The article describes the specificity of automatic post-editing in comparison with other tasks in machine translation, and it discusses how it may function as a complement to them. Particular detail is given in the article to the five-year period that covers the shared tasks presented in WMT conferences (2015-2019). In this period, discussion of automatic post-editing evolved from the definition of its main parameters to an announced demise, associated with the difficulties in improving output obtained by neural methods, which was then followed by renewed interest. The article debates the role and relevance of automatic post-editing, both as an academic endeavour and as a useful application in commercial workflows.


The cruciate ligaments in knee replacement.
The cruciate ligaments were resected with their bony insertions during total knee arthroplasty carried out in 12 patients with severe rheumatoid or osteoarthritis. The ligaments were examined histologically and biomechanically, using ten specimens from healthy adults as a control. A significant difference was found in the tensile stiffness and viscoelastic properties of the ligaments between the arthritic and the control group. The ligaments in the rheumatoid knees had a distinctly inferior tensile strength compared with the osteoarthritic knees. Total knee replacement, which also replaces ligament function, should therefore be considered in severely damaged rheumatoid knees.


Enzymatic basis for sialyl-Tn expression in human colon cancer cells.
Sialyl-Tn antigen (SAalpha2-6 GalNAc alpha-Ser/Thr) is expressed as a cancer-associated antigen on the surface of cancer cells and its expression correlates with a poor prognosis in patients with colorectal and other adenocarcinomas. To understand the enzymatic basis of sialyl-Tn (STn) antigen expression, we used two clonal cell lines, LSB and LSC, derived from LS174T human colonic cancer cells. LSC cells express only the truncated carbohydrate antigen Tn (GalNAc alpha-Ser/Thr) and sialyl-Tn on their mucin molecules, whereas LSB cells express elongated oligosaccharide chains. Both cell lines demonstrated similar activities of glycosyltransferases involved in the biosynthesis of elongated and terminal structures of complex O-glycans. However, LSC cells were unable to synthesize core 1 (Gal beta1-3GalNAc-) because the ubiquitous enzyme activity of UDP-Gal:GalNAc-R beta3-Gal-transferase (core 1 beta3-Gal-transferase) was lacking. Core 1 beta3-Gal-transferase could not be reactivated in LSC cells by treatment with sodium butyrate or by in vivo growth of LSC cells in nude mice. In contrast, LSB cells were able to synthesize and process core 1 and core 2 (GlcNAc beta1-6 (Gal beta1-3) GalNAc-). LSC cells represent the first example of a non-hematopoietic cell line which lacks core 1 beta3-Gal-transferase activity. The lack of core 1 beta3-Gal-transferase in LSC cells explains why they are incapable of forming the common mucin O-glycan core structures and are committed to synthesizing the short Tn and STn oligosaccharides. These findings suggest that the activity of core 1 beta3-Gal-transferase is an important determinant of the STn phenotype of colon cancer cells.


Domestic violence and self-poisoning in Sri Lanka.
There is increasing evidence that domestic violence (DV) is an important risk factor for suicidal behaviour. The level of risk and its contribution to the overall burden of suicidal behaviour among men and women has not been quantified in South Asia. We carried out a large case-control study to examine the association between DV and self-poisoning in Sri Lanka. Cases (N = 291) were patients aged ⩾18 years, admitted to a tertiary hospital in Kandy Sri Lanka for self-poisoning. Sex and age frequency matched controls were recruited from the hospital's outpatient department (N = 490) and local population (N = 450). Exposure to DV was collected through the Humiliation, Afraid, Rape, Kick questionnaire. Multivariable logistic regression models were conducted to estimate the association between DV and self-poisoning, and population attributable fractions were calculated. Exposure to at least one type of DV within the previous 12 months was strongly associated with self-poisoning for women [adjusted OR (AOR) 4.08, 95% CI 1.60-4.78] and men (AOR 2.52, 95% CI 1.51-4.21), compared to those reporting no abuse. Among women, the association was strongest for physical violence (AOR 14.07, 95% CI 5.87-33.72), whereas among men, emotional abuse showed the highest risk (AOR 2.75, 95% CI 1.57-4.82). PAF% for exposure to at least one type of DV was 38% (95% CI 32-43) in women and 22% (95% CI 14-29) in men. Multi-sectoral interventions to address DV including enhanced identification in health care settings, community-based strategies, and integration of DV support and psychological services may substantially reduce suicidal behaviour in Sri Lanka.


[Somatic Embryogenesis in Pinus pumila and Productivity of Embryogenic Lines during Long-Term Cultivation In Vitro].
Zygotic embryos and megagametophytes of Pinus pumila for cultivation in vitro were transferred in 1/2 LV medium supplemented with growth regulators 2,4-dichlorophenoxyacetic acid (2,4-D) and benzylaminopurine (6-BAP) to induce somatic embryogenesis. Four stably proliferating cell lines from two genotypes were derived. The cell lines differed in the number of globular somatic embryos and the weight of embryogenic calli. Cells of these lines were multiplied as a result of somatic polyembryogenesis via cleavage. In the nutrient medium for maturation, mature somatic embryos were obtained. However, somatic embryos of not all embryogenic cell lines reached maturation. In this study, plantlets were obtained in an in vitro culture for the first time.


A novel gap-PCR with high resolution melting analysis for the detection of α-thalassaemia Southeast Asian and Filipino β°-thalassaemia deletion.
Homozygosity for the α-thalassaemia Southeast Asian (α-SEA) and Filipino β°-thalassaemia (β-FIL) deletions can cause serious complications leading to foetal death or life-long blood transfusions. A rapid and accurate molecular detection assay is essential in populations where the deletions are common. In this study, gap-polymerase chain reaction (PCR) with high resolution melting (HRM) analysis was developed to detect both the large deletions. Melting curves at 86.9 ± 0.1 °C were generated by normal individuals without the α-SEA deletion, 84.7 ± 0.1 °C by homozygous α-SEA deletion individuals and two melting curves at 84.7 ± 0.1 °C and 86.9 ± 0.1 °C by α-SEA deletion carriers. Normal individuals without the β-FIL deletion produce amplicons with a melting temperature (Tm) at 74.6 ± 0.1 °C, homozygous β-FIL individuals produce amplicons with Tm at 73.6 ± 0.1 °C and heterozygous β-FIL individuals generate two amplicons with Tm at 73.6 ± 0.1 °C and 74.6 ± 0.1 °C. Evaluation using blinded tests on 220 DNA samples showed 100% sensitivity and specificity. The developed assays are sensitive and specific for rapid molecular and prenatal diagnosis for the α-SEA and β-FIL deletions.


The impact of decentralisation on health systems in fragile and post-conflict countries: a narrative synthesis of six case studies in the Indo-Pacific.
A health system has three key stakeholders, the State-at national and subnational levels-the health service providers and the citizens. In most settings and especially in peacetime, these stakeholders are typically well-defined. In contrast, during conflict and crisis as well as during ceasefire and post-conflict peacebuilding, stakeholders in the health system are often more diverse and contested. Health systems in such settings tend to be more decentralised, de facto-often in addition to de jure decentralisation. Despite much debate on the potential benefits of decentralisation, assessing its impact on health system performance remains difficult and its effect is open to dispute in the literature. This narrative synthesis aims to support efforts to assess and make sense of how decentralisation impacts health system performance in fragile and post-conflict countries-by synthesising evidence on the impact of decentralisation on health system performance from six country case studies: Papua New Guinea, the Philippines, Indonesia, Pakistan, Myanmar and Nepal. The impact of decentralisation on health system performance is optimised when combining centralisation (e.g., the benefits of central coordination in improving efficiency) with decentralisation (e.g., the benefits of local decision making in improving equity and resilience). The findings may inform efforts to think through what to centralise or decentralise, the impacts of those choices, and how the impact may change over time as countries go through and emerge from conflict-and as they go through and recover from the Covid-19 pandemic and prepare for future pandemics.


A bZIP protein, VIP1, interacts with Arabidopsis heterotrimeric G protein β subunit, AGB1.
Heterotrimeric G proteins (Gα, Gβ, Gγ) are signaling molecules conserved among eukaryotic species. The G proteins transmit signals via protein-protein interactions. By a yeast two-hybrid screen, we identified a bZIP protein, VIP1, as an Arabidopsis thaliana Gβ (AGB1)-interacting partner. The interaction between AGB1 and VIP1 was confirmed by an in vitro GST pull-down assay and a bimolecular fluorescence complementation (BiFC) assay. VIP1 was previously reported to be a regulator of osmosensory signaling. Interestingly, the BiFC pattern between AGB1 and VIP1 was speckled when cells were incubated in a hypotonic solution, but not when cells were incubated in a mannitol-containing hypertonic solution, suggesting that the subcellular localization of the AGB1-VIP1 complex is regulated by extracellular osmolarity and/or turgor pressure.


Serum extracellular traps associate with the activation of myeloid cells in SLE patients with the low level of anti-DNA antibodies.
Neutrophil extracellular traps (NETs) are involved in systemic lupus erythematosus (SLE). We sought to cluster SLE patients based on serum NET levels. Serum NET levels were higher in SLE patients than healthy controls. Frequencies of pleuritis and myositis were increased in patients with high serum NET levels. Serum NET levels negatively correlated with anti-double stranded DNA (anti-dsDNA) antibody titers and C1q-binding immune complexes, but positively correlated with C-reactive protein (CRP) and monocyte counts. Neutrophil transcriptome analysis demonstrated no difference in NET-associated signatures, irrespective of serum NET levels, suggesting anti-dsDNA antibody-mediated clearance of NETs. In serum, NET levels were significantly correlated with myeloid cell-derived inflammatory molecules. Serum NET-based cluster analysis revealed 3 groups of patients based on serum NET and CRP levels, anti-dsDNA antibody titers, and monocyte count. Monocytes were consistently activated following NET-containing immune complex (NET-IC) stimulation. In conclusion, SLE patients with high serum NET levels had lower anti-dsDNA antibody titers and higher inflammatory responses. NET-IC-stimulated monocytes might associate with an inflammatory response characterized by elevated CRP levels. These findings can apply to precision medicine, as inflammatory processes, rather than antibody-dependent processes, can be targeted in specific subpopulations of SLE patients.


Validation of a questionnaire and microenvironmental model for estimating past exposures to ozone.
Epidemiology studies of the health effects associated with chronic exposure to ozone are constrained by a lack of validated exposure assessment methods that account for activity patterns and building ventilation, two potentially important predictors of ozone exposure. A pilot study was conducted to evaluate the impact of these parameters on an exposure model, to evaluate how reliably they can be reconstructed, and how this reliability affects estimates of past exposures to ozone. Fourteen subjects completed time-activity diaries and wore personal passive monitors during summer 1996 and reconstructed their activities 1 year later in a questionnaire. These data were used in a microenvironmental exposure model and the results were compared to measured personal exposure. A model using activity patterns, building ventilation, and location-specific ambient ozone data produced mean exposure estimates 18.9 +/- 1.5 ppb ozone greater than personal measurements. A simpler model that omitted variation in indoor ventilation produced exposure estimates 5.0 +/- 1.3 ppb ozone greater than mean measured exposures. The questionnaire was a reliable survey method for reconstructing past activity patterns. However, detailed histories of building ventilation may not be required to reconstruct reliably past exposures to ozone. The simple model was more precise and more practical for implementation in large epidemiological studies of health effects related to chronic exposure to ambient ozone.


Effects of reinforcer delay and variability in a successive-encounters procedure.
Pigeons responded in a successive-encounters procedure that consisted of a search period, a choice period, and a handling period. The search period was either a fixed-interval or a mixed-interval schedule presented on the center key of a three-key chamber. Upon completion of the search period, the center key was turned off and the two side keys were lit. A pigeon could either accept a delay followed by food (by pecking the right key) or reject this option and return to the search period (by pecking the left key). During the choice period, a red right key represented the long alternative (a long handling delay followed by food), and a green right key represented the short alternative (a short handling delay followed by food). The experiment consisted of a series of comparisons for which optimal diet theory predicted no changes in preference for the long alternative (because the overall rates of reinforcement were unchanged), whereas the hyperbolic-decay model predicted changes in preference (because the delays to the next possible reinforcer were varied). In all comparisons, the results supported the predictions of the hyperbolic-decay model, which states that the value of a reinforcer is inversely related to the delay between a choice response and reinforcer delivery.


Effect of the XbaI polymorphism of estrogen receptor alpha on postmenopausal gray matter.
The frequent polymorphism XbaI (A351G) in the estrogen receptor alpha (ERalpha) gene has been associated with some postmenopausal pathologies' risk such as Alzheimer's disease (AD) or cognitive decline. In the present study, we explored whether the XbaI polymorphism leads to different gray matter volumes using voxel-based morphometry (VBM) on 20 magnetic resonance images of healthy postmenopausal women. Subjects carrying the less common XbaI/X allele were contrasted to non-carriers in groups well balanced by relevant confounding variables. The XbaI/X allele carriers displayed clusters ranging from 9 to 28% of tissue reductions in the cerebellar (cluster size, z, stereotactic coordinates: 16 mm(3); 3.17; 14, -94, -38) and cerebral cortex, in particular in the occipital lobe (272 mm(3); 3.76; -38,-68,-16), in the middle frontal gyrus (192 mm(3); 3.71; 38, 12, 38) and in the middle temporal gyrus, while the opposite comparison was negative. The XbaI/X allele in ERalpha gene is associated to smaller gray matter volumes of the cerebral and cerebellar cortex. This allele might increase the susceptibility for senile neurodegenerative conditions, being associated to smaller cerebral reserve.


Epitope mapping from real time kinetic studies - role of crosslinked disulphides and incidental interacting regions in affinity measurements: study with human chorionic gonadotropin and monoclonal antibodies.
Real time kinetic studies were used to map conformational epitopes in human chorionic gonadotropin (hCG) for two monoclonal antibodies (MAbs). The epitopes were identified in the regions (alpha 5--14 and alpha 55--62). The association rate constant (k+1) was found to be altered by chemical modification of hCG, and the ionic strength of the reaction medium. Based on these changes, we propose the presence of additional interactions away from the epitope- paratope region in the hCG-MAb reaction. We have identified such incidental interacting regions (IIRs) in hCG to be the loop region alpha 35--47 and alpha 60--84. The IIRs contribute significantly towards the KA of the interaction. Therefore, in a macromolecular interaction of hCG and its MAb, KA is determined not only by epitopeparatope interaction but also by the interaction of the nonepitopic-nonparatopic IIRs. However, the specificity of the interaction resides exclusively with the epitope-paratope pair.


Isolation and sequence polymorphism of a rat retinoblastoma (RB) cDNA.
A cDNA of the rat retinoblastoma gene (RB) was prepared from total RNA of rat liver using reverse transcription-polymerase chain reaction (RT-PCR). The 4432-nt sequence isolated contained 2700-nt translated and 1732-nt 3'-untranslated regions (UTR). The isolated cDNA detected poly(A)+RNAs of 5.4 and 3.4 kb in rat liver and kidney by Northern blot hybridization. The nt sequence of the isolated cDNA had 85% homology with that of mouse and 73% with human. The 899-amino-acid (aa) sequence was 95% homologous to that of mouse and 90% to human. The aa sequences of two functional domains of oncoprotein-binding and ten putative phosphorylation sites regulating RB function were conserved in the three species. However, the 3'-UTR were less homologous among the three, and had polymorphism in three portions, even in rats. These polymorphisms were strain-specific and genetically segregated. Thus, the rat RB cDNA and its sequence information may be useful for clarifying the role of the RB protein and genetic linkage analysis in basic biomedical research using rats, especially in experimental carcinogenesis.


Hemiballism. Clinico-pathological conference.
A case of left hemiballism is presented. Besides multiple lacunar infarcts an haemorrhage in the contralateral subthalamic nucleus is shown. A short review of the literature is given with special attention to the etiology and the therapy.


Natural remedies used by Bunong people in Mondulkiri province (Northeast Cambodia) with special reference to the treatment of 11 most common ailments.
In this paper we present a comprehensive ethnomedicinal study conducted in Mondulkiri province. Traditional knowledge about natural medicine (plants, animals, mushrooms) was investigated in Cambodia's largest indigenous community: the Bunong people. The survey aims to document the medicinal plant use of this ethnic, by focusing on the eleven most frequent diseases encountered in the area, in order to highlight species that could be recommended in public health programs. During the years 2013 and 2014, 202 villagers were interviewed in 28 villages from the five districts in Mondulkiri. Two types of methodology were employed: (1) an ethnobotanical field survey (walk-in-the-wood interviews) and (2) semi-structured household interviews with a special emphasis on the treatment of 11 most common ailments encountered in the area. Medicinal plants and mushrooms were collected and identified together with medicinal animals. The factor informant consensus (FIC) and fidelity level (FL) were calculated. Bunong people use a total of 214 plants belonging to 72 families, 1 mushroom and 22 animal species in their traditional healthcare practices in order to treat 51 different ailments. Among the medicinal plants, Fabaceae was the most predominant family; Chromolaena odorata (L.) R.M. King and H.Rob. (Asteraceae), Zingiber montanum (J.Koenig) Link ex A.Dietr. (Zingiberaceae) and Kalanchoe pinnata (Lam.) Pers. (Crassulaceae) were the most cited medicinal plants; and four ailments (cold/fever, diarrhea, postpartum disorders and stomachache) were described as major ailments in the community. The root was the most important part of plants used, and decoction was the most cited method of preparation. During our survey, we also discovered a "new to science" plant species called Ardisia mondulkiriensis Hul and Chassagne, and we recorded for the second time the plant species recently described, Solanum sakhanii Hul. Most of the species reported for the treatment of the 11 most frequent ailments have already been proven to be efficient and safe. Furthermore, 10 plant species are reported for the first time as medicinal and some of them are widely used in the community. Further pharmacological and phytochemical investigations should be undergone to assess the pharmaceutical potential of these species. While undergoing considerable changes, Bunong people have maintained extensive traditional medicine knowledge. As this indigenous hill tribe depend mainly on natural remedies for their daily healthcare, environmental preservation is of high importance for the community.


NFAT4-dependent miR-324-5p regulates mitochondrial morphology and cardiomyocyte cell death by targeting Mtfr1.
Emerging evidence suggest that the abnormal mitochondrial fission participates in pathogenesis of cardiac diseases, including myocardial infarction and heart failure. However, the molecular components regulating mitochondrial network in heart remain largely unidentified. Here we report that NFAT4, miR-324-5p and mitochondrial fission regulator 1 (Mtfr1) function in one signaling axis that regulates mitochondrial morphology and cardiomyocyte cell death. Knocking down Mtfr1 suppresses mitochondrial fission, apoptosis and myocardial infarction. Mtfr1 is a direct target of miR-324-5p, and miR-324-5p attenuates mitochondrial fission, cardiomyocyte apoptosis and myocardial infarction by suppressing Mtfr1 translation. Finally, we show that transcription factor NFAT4 inhibits miR-324-5p expression. Knockdown of NFAT4 suppresses mitochondrial fission and protects cardiomyocyte from apoptosis and myocardial infarction. Our study defines the NFAT4/ miR-324-5p/Mtfr1 axis, which participates in the regulation of mitochondrial fission and cardiomyocyte apoptosis, and suggests potential new treatment avenues for cardiac diseases.


Chimeric peptides as modulators of CK2-dependent signaling: Mechanism of action and off-target effects.
Protein kinase CK2 is a tetrameric enzyme composed of two catalytic (α/α') and two regulatory (β) subunits. It has a global prosurvival function, especially in cancer, and represents an attractive therapeutic target. Most CK2 inhibitors available so far are ATP-competitive compounds; however, the possibility to block only the phosphorylation of few substrates has been recently explored, and a compound composed of a Tat cell-penetrating peptide and an active cyclic peptide, selected for its ability to bind to the CK2 substrate E7 protein of human papilloma virus, has been developed [Perea et al., Cancer Res. 2004; 64:7127-7129]. By using a similar chimeric peptide (CK2 modulatory chimeric peptide, CK2-MCP), we performed a study to dissect its molecular mechanism of action and the signaling pathways that it affects in cells. We found that it directly interacts with CK2 itself, counteracting the regulatory and stabilizing functions of the β subunit. Cell treatment with CK2-MCP induces a rapid decrease of the amount of CK2 subunits, as well as of other signaling proteins. Concomitant cell death is observed, more pronounced in tumor cells and not accompanied by apoptotic events. CK2 relocalizes to lysosomes, whose proteases are activated, while the proteasome machinery is inhibited. Several sequence variants of the chimeric peptide have been also synthesized, and their effects compared to those of the parental peptide. Intriguingly, the Tat moiety is essential not only for cell penetration but also for the in vitro efficacy of the peptide. We conclude that this class of chimeric peptides, in addition to altering some properties of CK2 holoenzyme, affects several other cellular targets, causing profound perturbations of cell biology. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.


Safety and efficacy of transaxillary transcatheter aortic valve replacement using a current-generation balloon-expandable valve.
Transaxillary access (TAx) has shown promise as an excellent alternative TAVR option, but data on the Edwards SAPIEN 3 in TAx-TAVR is limited. We sought to study the safety and efficacy of TAx-TAVR using this current-generation balloon-expandable valve. A retrospective study of our first 24 TAx and 20 transthoracic (TT) TAVR patients treated with the SAPIEN 3 valve was performed, and the patients' preoperative characteristics, procedural outcomes, and clinical outcomes were compared to our first 100 transfemoral (TF) patients using the SAPIEN 3 device. There were no statistical differences observed for outcomes between the TAx and TF groups, despite the TAx patients having more comorbidities (STS-PROM 11.3 ± 7.6 versus 7.3 ± 5.2, p = 0.042). In addition, no significant difference was found in the fluoroscopy time and contrast amount between the two groups. The patients' baseline characteristics were similar between the TAx and TT groups. Their procedural and clinical outcomes were comparable, but there was a trend towards lower incidence of acute kidney injury (13.0% versus 23.5%), new-onset atrial fibrillation (5.6% versus 33.3%), shorter median length of stay postoperatively (4 versus 6 days), fewer discharges to rehabilitation (16.7% versus 35.0%), and a lower rate of readmission within 30-days (8.3% versus 35.0%), all favoring TAx access. TAx-TAVR with the SAPIEN 3 valve is a safe alternative to TF access. It offers advantages of improved recovery over TT access, and appears to be a superior alternative-access option for TAVR. TAx access could be preferred when TF access is not feasible.


Toxic effect of Callistemon viminalis essential oil on the ovary of engorged Rhipicephalus microplus female ticks (Acari: Ixodidae).
Rhipicephalus microplus is the main ectoparasite of cattle and its parasitism can reduce weight gain of hosts, in addition to causing anemia, increasing the risk of myiasis, and resulting in the transmission of Babesia bovis and Anaplasma marginale, among other pathogens. The use of synthetic chemicals plays an important role in controlling these ticks. However, its frequent and indiscriminate use has contributed to the selection of resistant strains, resulting in greater interest in the search for natural-origin products. The shrub Callistemon viminalis (Myrtaceae), also known as weeping bottlebrush, is known for its antibacterial, acaricidal, repellent, and antifungal activities, but there are no reports in the literature about its effects on the internal morphology of ticks. This study aimed to extract and characterize the essential oil obtained from the leaves of C. viminalis. Additionally, its effects on the ovary morphology of engorged R. microplus were assessed through histological, histochemical, and morphometric techniques. Exposure to C. viminalis caused dose-dependent morphological changes, such as cellular alterations in the epithelial layer lining the ovary lumen and the pedicel, irregularity of the chorion and oocyte shape, changes in protein and carbohydrate content, decrease in oocyte size, reduction in the size of the nucleus as well as cytoplasmic and nucleolar vacuolation. Thus, C. viminalis essential oil exhibited a toxic effect on the reproductive system of R. microplus, which may result in the reproductive impairment of this tick species.


Color Doppler Ultrasound versus Computed Tomography Angiography for Preoperative Anterolateral Thigh Flap Perforator Imaging: A Systematic Review and Meta-Analysis.
The anterolateral thigh (ALT) perforator flap is a commonly used flap with a predictable, though often variable, perforator anatomy. Preoperative imaging with color Doppler ultrasound (CDU) and computed tomography angiography (CTA) of ALT flap perforators can be a useful tool for flap planning. This study provides a complete review and analysis of the relevant preoperative ALT imaging literature. Studies related to preoperative CDU and CTA imaging were reviewed, and information related to imaging method, sensitivity, false-positive rates, and perforator course identification (musculocutaneous vs. septocutaneous) were analyzed. A total of 23 studies related to preoperative ALT flap CDU and CTA imaging were included for review and analysis. Intraoperative perforator identification was compared with those found preoperatively using CDU (n = 672) and CTA (n = 531). Perforator identification sensitivity for CDU was 95.3% (95% CI: 90.9-97.6%) compared with the CTA sensitivity of 90.4% (95% confidence interval [CI]: 74.4-96.9%). The false-positive rate for CDU was 2.8% (95% CI: 1.1-4.5%) compared with 2.4% (95% CI: 0.7-4.1%) for CTA. Accuracy of perforator course identification was 95.5% (95% CI: 93.6-99.2%) for CDU and 96.9% (95% CI: 92.7-100.1%) for CTA. CDU provides the reconstructive surgeon with greater preoperative perforator imaging sensitivity compared with CTA; however, false-positive rates are marginally higher with preoperative CDU. Preoperative imaging for ALT flap design is an effective tool, and the reconstructive surgeon should consider the data presented here when selecting a flap imaging modality.


Monoclonal antibodies against mesothelial membrane antigen discriminate between malignant mesothelioma and lung adenocarcinoma.
Monoclonal antibodies (MAbs) were generated by immunizing mice with the mesothelioma cell line SPC111 and selected by indirect immunofluorescence on viable cells. Indirect immunofluorescence staining and radioimmunoassays demonstrated selective binding of the antibodies ME1 and ME2 with the surface membrane of mesothelioma, but not with lung adenocarcinoma cell lines. Lung small-cell carcinoma cell lines were unreactive, while staining was seen in a proportion of lung squamous-cell carcinoma cell lines. The antibodies were unreactive with other cell lines, including breast, colon, ovarian, and renal-cell carcinoma, leukemia, and lung fibroblast. The antibodies stained normal mesothelial cells, but were unreactive with normal bronchial epithelial cells in primary cultures, or peripheral blood cells. Immunohistochemical staining of cryostat sections of tumor tissues confirmed the ability of the antibodies to distinguish between mesothelioma and lung adenocarcinoma. All 12 mesothelioma tissues, but none of 9 lung adenocarcinomas or large-cell carcinomas, stained with the MAbs. Staining of malignant mesothelioma tissues was very homogeneous. Some lung squamous-cell carcinomas and breast carcinomas were stained focally by both, and some ovarian carcinomas by one antibody. Solid-phase radioimmunoassays demonstrated antigen sensitivity to chymotrypsin digestion and binding competition between the antibodies. The antibodies ME1 and ME2 identify a surface membrane antigen with preferential expression on normal and malignant mesothelial cells. They distinguish malignant mesothelioma from lung adenocarcinoma on cryostat sections and promise to be useful tools in biological studies of mesothelial cells.