Subungual exostosis recurrence in a 16-year-old athletic male.
Subungual exostosis is a painful, benign bony outgrowth projecting from the distal phalanx of the toes. The present case consists of a 16-year-old male that presented to the primary clinic with a single circumscribed painful lesion underneath the nail of the first phalanx of the left foot that recurred after surgical extraction.


Naloxone fails to block substance P-induced excitation of spinal nociceptive units.
In chloralose-anaesthetized cats the iontophoretic application of substance P produced an excitation of dorsal horn nociceptive units, as found in earlier studies. Naloxone (0.1-0.2 mg/kg, IV) failed to abolish this response to substance P in any of the 9 cats studied. In 4 additional cats nociceptive units were tested with morphine (1.0-3.2 mg/kg, IV) and substance P in case the antinociceptive effect of descending pathways is mediated via an excitatory action, but in each case morphine and substance P produced opposite effects (depression and excitation, respectively), suggesting that this was not the case. The present results fail to support a naloxone-antagonizable inhibitory effect of substance P in the spinal cord.


Histopathologic characterization of chronic radiofrequency ablation lesions for pulmonary vein isolation.
This study describes the histopathologic and electrophysiological findings in patients with recurrence of atrial fibrillation (AF) after pulmonary vein (PV) isolation who underwent a subsequent surgical maze procedure. The recovery of PV conduction is commonly responsible for recurrence of AF after catheter-based PV isolation. Twelve patients with recurrent AF after acutely successful catheter-based antral PV isolation underwent a surgical maze procedure. Full-thickness surgical biopsy specimens were obtained from the PV antrum in areas of visible endocardial scar. Before biopsy, intraoperative epicardial electrophysiological recordings were taken from each PV using a circular mapping catheter. Twenty-two PVs were biopsied from the 12 patients 8 ± 11 months after ablation. Eleven of the 22 specimens (50%) revealed transmural scar, and 11 (50%) showed viable myocardium with or without scar. Each biopsy specimen demonstrated evidence of injury, most commonly endocardial thickening (n = 21 [95%]) and fibrous scar (n = 18 [82%]). Seven of the 22 specimens (32%) showed conduction block at surgery. Transmural scar was more likely to be seen in the biopsy specimens from the PVs with conduction block than in specimens from the PVs showing reconnection. However, viable myocardium alone or mixed with scar was seen in 2 specimens from PVs with conduction block. PVs showing electrical reconnection after catheter-based antral ablation frequently reveal anatomic gaps or nontransmural lesions at the sites of catheter ablation. Nontransmural lesions are noted in some PVs with persistent conduction block, suggesting that lesion geometry may influence PV conduction. The histological findings show that nontransmural ablation can produce a dynamic cellular substrate with features of reversible injury. Delayed recovery from injury may explain late recurrences of AF after PV isolation.


Qualitative and quantitative determination of micro-inclusions by automated SEM/EDX analysis.
With the help of an automated SEM/EDX analysis system non-metallic micro-inclusions in steel can be detected on a metallographically prepared surface area. The system makes it possible to determine position, size, shape and composition of each particle. Usually more than 1000 inclusions are found on one scan area. Therefore a new offline evaluation method has been developed to classify the large amount of inclusions and calculate specific size and shape data. A summary sheet is created to show the area contents and the mean values of all important properties for each class. Size and XY distributions as well as binary and ternary phase diagrams are drawn to depict the results. The strengths of this analytical technique are demonstrated by evaluation of an LC (low-carbon) steel. Alumina, common spinel, sulfide and oxisulfide inclusions could be identified as dominant inclusion types in LC steel.


Targeting Notch degradation system provides promise for breast cancer therapeutics.
Notch receptor signaling pathways play an important role, not only in normal breast development but also in breast cancer development and progression. As a group of ligand-induced proteins, different subtypes of mammalian Notch (Notch1-4) are sensitive to subtle changes in protein levels. Thus, a clear understanding of mechanisms of Notch protein turnover is essential for understanding normal and pathological mechanisms of Notch functions. It has been suggested that there is a close relationship between the carcinogenesis and the dysregulation of Notch degradation. However, this relationship remains mostly undefined in the context of breast cancer, as protein degradation is mediated by numerous signaling pathways as well as certain molecule modulators (activators/inhibitors). In this review, we summarize the published data regarding the regulation of Notch family member degradation in breast cancer, while emphasizing areas that are likely to provide new therapeutic modalities for mechanism-based anti-cancer drugs.


Fe(3+)-functionalized carbon quantum dots: A facile preparation strategy and detection for ascorbic acid in rat brain microdialysates.
This study reports an Fe(3+)-functionalized carbon quantum dots (Fe(3+)-functionalized CQDs) for the highly sensitive and selective detection of ascorbic acid (AA) in rat brain microdialysates based on the specific redox reaction between iron(III) ions and AA. The carbon quantum dots (CQDs) were synthesized by one-step pyrolysis of a small organic molecules i.e. tris(hydroxymethyl)aminomethane (Tris). Fe(3+) can tightly chelate to the surface of CQDs by the hydroxyl group to form Fe(3+)-functionalized CQDs while the fluorescence of CQDs can be effectively quenched by Fe(3+) via Fluorescence resonance energy transfer (FRET). The fluorescence of the Fe(3+)-functionalized CQDs can be sensitively turned on by AA to give an "on-off-on" fluorescence response through the oxidation-reduction between Fe(3+) and AA since the produced Fe(2+) has much lower chelating ability to CQDs and the fluorescence of CQDs can be restored. This Fe(3+)-functionalized CQDs based nanoprobe shows high selective and sensitive response in the concentration of AA ranging from 0.1 μM to 50 μM with the detection limit as lower as 9.1 nM, which is lower than other assays. Finally, the proposed fluorescent probe was successfully applied to direct analysis of AA in biological fluids, i.e. rat brain microdialysates, and may pave a new route to the design of effective carbon quantum dots-based fluorescence probes for other bioassay.


Production of finely graded forces in humans: effects of simulated weightlessness by water immersion.
We have shown before that subjects exposed to a changed gravitoinertial environment produce exaggerated manual forces. From the observed pattern of findings, we argued that initial forces were exaggerated because of abnormal vestibular activity and peak forces because of degraded proprioceptive feedback. If so, only peak but not initial forces should be affected by water immersion, an environment that influences proprioceptive feedback but not vestibular activity. The present study was undertaken to scrutinize this prediction. Twelve subjects sat in a chair once immersed in water and once on dry land, while producing pre-trained isometric forces with a joystick. In a control experiment, subjects performed a four-choice reaction-time task. During the joystick task, produced initial forces were comparable in water and on land, while peak (+24%) and end forces (+22%) were significantly higher in water, as was their reaction time (+6%). During the control task, reaction time was comparable in water and on land. Our findings corroborate the above notion that initial forces increase when the vestibular system is stimulated (gravitoinertial change, visual field motion, but not water immersion), while peak forces increase when proprioceptive feedback is degraded (probably all three scenarios) and are not corrected until response end. Our findings further confirm the absence of cognitive slowing in simple-choice reaction tasks under shallow-water immersion conditions.


Medullary thyroid carcinoma and pheochromocytoma accompanied with nodular hyperplasia in multiple endocrine neoplasia type 2.
Three patients with familial multiple endocrine neoplasia type 2 underwent total adrenalectomy and subsequently near-total or total thyroidectomy. The overt pheochromocytomas were present bilaterally in two patients and unilaterally in another patient. In addition, multiple nodules measuring a few mm in diameter were demonstrated in all adrenal medullas examined. All patients exhibited bilateral medullary thyroid carcinomas which varied in size from a few minute nodules accompanied by the microscopic C-cell hyperplasia to distinct large tumors. The thyroid C-cell hyperplasia appeared to be confined to the upper and middle thirds of the lateral lobe, and micronodules of the C-cell hyperplasia enlarged to coalesce, forming one large carcinoma mass. On the other hand, nodular hyperplasia of the chromaffin cells was distributed diffusely throughout the adrenal medulla and each nodule appeared to develop individually into a large pheochromocytoma. These findings suggested that, at least in the family members at a high risk for multiple endocrine neoplasia type 2, the development of both medullary thyroid carcinoma and pheochromocytoma was always preceded by a multicentric nodular hyperplasia. On the basis of the pathogenesis of these tumors, the most rational surgical approach was presented.


Emerging Targeted Therapies for the Treatment of Non-small Cell Lung Cancer.
Lung cancer remains the leading cause of cancer-related mortality worldwide. Genetic and molecular profiling of non-small cell lung cancer (NSCLC) has led to the discovery of actionable oncogenic driver alterations, which has revolutionized treatment for this disease. This review will move beyond traditional mutational drivers such as EGFR and ALK and will instead focus on emerging targets and the efficacy of new precision therapies. Here, we discuss both established and emerging targeted therapy approaches, as well as ongoing challenges for the treatment of NSCLC patients harboring oncogenic alterations of the following types-gene fusions (ROS1, RET, NTRK), receptor tyrosine kinases (MET amplification and exon 14 mutations and EGFR/HER2 exon 20 insertion mutations), and MAPK signaling (SHP2 and altered BRAF and NF1). The treatment of lung cancer is increasingly biomarker-driven, as patients are selected for targeted agents based on the identification of genetic alterations amenable to inhibition. Our ability to further improve patient outcomes with this precision medicine approach will require continued efforts to identify, characterize, and target lesions driving lung cancer tumorigenesis and progression.


The differentiation of invasive and non-invasive Entamoeba histolytica by isoenzyme electrophoresis.
Cultures of 85 stocks of Entamoeba histolytica were compared by electrophoretic patterns of three enzymes: glucosephosphate isomerase, phosphoglucomutase and L-malate: NADP+ oxidoreductase (oxaloacetate-decarboxylating). Four groups of E. histolytica stocks have been distinguished. 18 of these stocks were derived from individual patients with clinical amoebiasis and all of these were of one enzyme group, which did not occur among the other stocks.


A case control investigation of COVID-19 associated mucormycosis in India.
Increased occurrence of mucormycosis during the second wave of COVID-19 pandemic in early 2021 in India prompted us to undertake a multi-site case-control investigation. The objectives were to examine the monthly trend of COVID-19 Associated Mucormycosis (CAM) cases among in-patients and to identify factors associated with development of CAM. Eleven study sites were involved across India; archived records since 1st January 2021 till 30th September 2021 were used for trend analysis. The cases and controls were enrolled during 15th June 2021 to 30th September 2021. Data were collected using a semi-structured questionnaire. Among 1211 enrolled participants, 336 were CAM cases and 875 were COVID-19 positive non-mucormycosis controls. CAM-case admissions reached their peak in May 2021 like a satellite epidemic after a month of in-patient admission peak recorded due to COVID-19. The odds of developing CAM increased with the history of working in a dusty environment (adjusted odds ratio; aOR 3.24, 95% CI 1.34, 7.82), diabetes mellitus (aOR: 31.83, 95% CI 13.96, 72.63), longer duration of hospital stay (aOR: 1.06, 95% CI 1.02, 1.11) and use of methylprednisolone (aOR: 2.71, 95% CI 1.37, 5.37) following adjustment for age, gender, occupation, education, type of houses used for living, requirement of ventilatory support and route of steroid administration. Higher proportion of CAM cases required supplemental oxygen compared to the controls; use of non-rebreather mask (NRBM) was associated as a protective factor against mucormycosis compared to face masks (aOR: 0.18, 95% CI 0.08, 0.41). Genomic sequencing of archived respiratory samples revealed similar occurrences of Delta and Delta derivates of SARS-CoV-2 infection in both cases and controls. Appropriate management of hyperglycemia, judicious use of steroids and use of NRBM during oxygen supplementation among COVID-19 patients have the potential to reduce the risk of occurrence of mucormycosis. Avoiding exposure to dusty environment would add to such prevention efforts.


Using Cone-Beam Computed Tomography to Determine the Prevalence of the Second Mesiobuccal Canal in Maxillary First Molar Teeth in a Sample of an Iraqi Population.
This study aimed to determine the prevalence of the second mesiobuccal canal in maxillary first molar teeth in a sample of population from Basrah city in the south of Iraq. Cone-beam computed tomography (CBCT) images of 353 Iraqi patients from Basrah city were included in the study. These images revealed 691 maxillary first molars, but only 655 of them were included. The images were obtained using a Gendex (GXDP-7000) CBCT machine (Hatfield, PA, USA) and studied for the prevalence of second mesiobuccal canal in the mesiobuccal root canal configuration, according to Vertucci's classification, by scrolling through the images. Pearson's chi-square tests were used to correlate canal type distribution to gender and age. The distributions of canal type on the right and left sides were assessed using the Kendal tau correlation coefficient. A P-value <0.001 was considered highly significant. For intra-examiner reliability analysis, Cohen's kappa test was used. The second mesiobuccal canal was identified in 81.68% of the Iraqi population sample. The most common type was type II (44.58%), followed by type IV (31.30%). Type I occurred in 18.32% of cases. Other types were less frequent. The second mesiobuccal canal occurred in most of the examined samples of the Iraqi population (81.68%), with the most common type being type II, followed by type IV.


Are patients with esophageal cancer who become PET negative after neoadjuvant chemoradiation free of cancer?
Esophageal cancer continues to increase in incidence. Many patients are presenting with stage II or greater disease and proceeding to neoadjuvant chemoradiation therapy before resection. Approximately 30% of patients will achieve a complete response and might not benefit from proceeding to resection. This study will examine the ability of PET to predict patients with a complete pathologic response. A query of our IRB-approved esophageal database revealed 81 patients who underwent a pre- and postchemoradiation PET scan and then proceeded to esophageal resection. Statistical analysis was performed to determine the ability of PET to predict a complete pathologic response. When comparing posttherapy PET with final pathology, it was determined that PET could not consistently differentiate a complete pathologic response from patients who still had persistent disease. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 61.8%, 43.8%, 70%, 35%, and 56%, respectively, for patients with a complete PET response after neoadjuvant therapy. A complete PET response after neoadjuvant chemoradiation is not substantially predictive of a complete pathologic response. Patients should still be referred for resection unless distant metastases are identified.


Modulation of skyrmionic magnetic textures in two-dimensional vdW materials and their heterostructures.
The intrinsic magnetism observed in two-dimensional (2D) van der Waals (vdW) materials provides a unique opportunity for exploring the 2D topological magnetic textures, in particular skyrmionic magnetic textures (SMTs) including skyrmion and its topological equivalents. Since the experimental discovery of skyrmions in the 2D vdW materials and their heterostructures, a critical challenge lies in the control of these SMTs to translate their intriguing features into spintronic applications. Here, we review the recent experimental and theoretical progress on the modulations of SMTs in 2D vdW monolayer materials and their heterostructures. Besides well-established basic modulation factors including temperature, magnetic field and sample thickness, we present the experimental realization of mobility and transition driven by electric current, and the theoretical prediction of diverse magnetoelectric modulations by electric field. Considering the 2D character of vdW layered materials, strain and stacking style are also efficient approaches to tune the magnetic textures.


Knowing the enemy: homoacetogens in hydrogen production reactors.
One of the bottlenecks of the hydrogen production by dark fermentation is the low yields obtained because of the homoacetogenesis persistence, a metabolic pathway where H2 and CO2 are consumed to produce acetate. The central reactions of H2 production and homoacetogenesis are catalyzed by enzyme hydrogenase and the formyltetrahydrofolate synthetase, respectively. In this work, genes encoding for the formyltetrahydrofolate synthetase (fthfs) and hydrogenase (hydA) were used to investigate the diversity of homoacetogens as well as their phylogenetic relationships through quantitative PCR (qPCR) and next-generation amplicon sequencing. A total of 70 samples from 19 different H2-producing bioreactors with different configurations and operating conditions were analyzed. Quantification through qPCR showed that the abundance of fthfs and hydA was strongly associated with the type of substrate, organic loading rate, and H2 production performance. In particular, fthfs sequencing revealed that homoacetogens diversity was low with one or two dominant homoacetogens in each sample. Clostridium carboxivorans was detected in the reactors fed with agave hydrolisates; Acetobacterium woodii dominated in systems fed with glucose; Blautia coccoides and unclassified Sporoanaerobacter species were present in reactors fed with cheese whey; finally, Eubacterium limosum and Selenomonas sp. were co-dominant in reactors fed with glycerol. Altogether, quantification and sequencing analysis revealed that the occurrence of homoacetogenesis could take place due to (1) metabolic changes of H2-producing bacteria towards homoacetogenesis or (2) the displacement of H2-producing bacteria by homoacetogens. Overall, it was demonstrated that the fthfs gene was a suitable marker to investigate homoacetogens in H2-producing reactors. KEY POINTS: • qPCR and sequencing analysis revealed two homoacetogenesis phenomena. • fthfs gene was a suitable marker to investigate homoacetogens in H2 reactors.


Comparison of the Diversity of Basidiomycetes from Dead Wood of the Manchurian fir (Abies holophylla) as Evaluated by Fruiting Body Collection, Mycelial Isolation, and 454 Sequencing.
In this study, three different methods (fruiting body collection, mycelial isolation, and 454 sequencing) were implemented to determine the diversity of wood-inhabiting basidiomycetes from dead Manchurian fir (Abies holophylla). The three methods recovered similar species richness (26 species from fruiting bodies, 32 species from mycelia, and 32 species from 454 sequencing), but Fisher's alpha, Shannon-Wiener, Simpson's diversity indices of fungal communities indicated fruiting body collection and mycelial isolation displayed higher diversity compared with 454 sequencing. In total, 75 wood-inhabiting basidiomycetes were detected. The most frequently observed species were Heterobasidion orientale (fruiting body collection), Bjerkandera adusta (mycelial isolation), and Trichaptum fusco-violaceum (454 sequencing). Only two species, Hymenochaete yasudae and Hypochnicium karstenii, were detected by all three methods. This result indicated that Manchurian fir harbors a diverse basidiomycetous fungal community and for complete estimation of fungal diversity, multiple methods should be used. Further studies are required to understand their ecology in the context of forest ecosystems.


Struma ovarii with atypical features and synchronous primary thyroid cancer: a case report and review of the literature.
To present a case of struma ovarii with a typical features and synchronous primary thyroid carcinoma and review the available literature to guide diagnosis and management of these tumors. We present a case from our hospital of a 55-year-old woman who had an adnexal mass with features concerning for papillary thyroid carcinoma and was ultimately determined to be struma ovarii with atypical features. Subsequent thyroid imaging and biopsy revealed a primary cervical thyroid carcinoma. We performed a PubMed search of published English language articles using the search terms "malignant struma ovarii," "metastatic struma ovarii," "struma ovarii with malignant transformation," "struma ovarii papillary thyroid carcinoma," "struma ovarii follicular thyroid carcinoma," and "struma ovarii with concurrent primary thyroid carcinoma." Literature review included 104 studies with a total of 195 patient cases. The average age at presentation was 44.9 years. 25.1% of patients had metastatic disease at presentation, and 6.2% had synchronous primary carcinomas; all of which were located in the thyroid. Thyroid carcinoma arising in struma ovarii or mature cystic teratoma should prompt clinical evaluation and imaging of the thyroid given the possibility of synchronous primaries, metastases, and recurrence.


A sporadic juvenile case of the amyotrophic lateral sclerosis with neuronal intracytoplasmic inclusions.
In an autopsy case of the sporadic juvenile ALS (a 17-year-old girl) intracytoplasmic inclusions are found in the upper and lower motor neurons and in nerve cells of the dentate nucleus, pontine nucleus, brain stem reticular formation, substantia nigra, thalamus, globus pallidus and others. Histochemically they contain RNA-Protein compounds. Electron microscopically, they consist of randomly interwoven tubules with granular endoplasmic reticulums and free ribosomes in the margin. Each tubule measures 90--150 A in diameter and shows no distinct periodic constiction. Amorphous substances as well as ribosome granules are scattered and associated with those tubules. The inclusion-bearing cells are usually swollen and chromatolytic and have a large hydropic nucleus, suggesting a close relation between the development of the inclusion and chromatolysis. Clinically, a rapid progress of the symptoms (total duration: about 12 months) and conspicuous disturbances of the autonomic nerve, such as sinus tachycardia and bladder sphincter dysfunction, should be noticed.


Treatment of critically ill patients with cefiderocol for infections caused by multidrug-resistant pathogens: review of the evidence.
Appropriate antibiotic treatment for critically ill patients with serious Gram-negative infections in the intensive care unit is crucial to minimize morbidity and mortality. Several new antibiotics have shown in vitro activity against carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat resistant Pseudomonas aeruginosa. Cefiderocol is the first approved siderophore beta-lactam antibiotic with potent activity against multidrug-resistant, carbapenem-resistant, difficult-to-treat or extensively drug-resistant Gram-negative pathogens, which have limited treatment options. The spectrum of activity of cefiderocol includes drug-resistant strains of Acinetobacter baumannii, P. aeruginosa, Stenotrophomonas maltophilia, Achromobacter spp. and Burkholderia spp. and CRE that produce serine- and/or metallo-carbapenemases. Phase 1 studies established that cefiderocol achieves adequate concentration in the epithelial lining fluid in the lung and requires dosing adjustment for renal function, including patients with augmented renal clearance and continuous renal-replacement therapy (CRRT); no clinically significant drug-drug interactions are expected. The non-inferiority of cefiderocol versus high-dose, extended-infusion meropenem in all-cause mortality (ACM) rates at day 14 was demonstrated in the randomized, double-blind APEKS-NP Phase 3 clinical study in patients with nosocomial pneumonia caused by suspected or confirmed Gram-negative bacteria. Furthermore, the efficacy of cefiderocol was investigated in the randomized, open-label, pathogen-focused, descriptive CREDIBLE-CR Phase 3 clinical study in its target patient population with serious carbapenem-resistant Gram-negative infections, including hospitalized patients with nosocomial pneumonia, bloodstream infection/sepsis, or complicated urinary tract infections. However, a numerically greater ACM rate with cefiderocol compared with BAT led to the inclusion of a warning in US and European prescribing information. Cefiderocol susceptibility results obtained with commercial tests should be carefully evaluated due to current issues regarding their accuracy and reliability. Since its approval, real-world evidence in patients with multidrug-resistant and carbapenem-resistant Gram-negative bacterial infections suggests that cefiderocol can be efficacious in certain critically ill patient groups, such as those requiring mechanical ventilation for COVID-19 pneumonia with subsequently acquired Gram-negative bacterial superinfection, and patients with CRRT and/or extracorporeal membrane oxygenation. In this article, we review the microbiological spectrum, pharmacokinetics/pharmacodynamics, efficacy and safety profiles and real-world evidence for cefiderocol, and look at future considerations for its role in the treatment of critically ill patients with challenging Gram-negative bacterial infections.


Diagnosis and Treatment of Typhoid Fever and Associated Prevailing Drug Resistance in Northern Ethiopia.
To determine diagnostic value of the Widal test, treatment pattern of febrile patients and antimicrobial drug susceptibility pattern of blood isolates. Using cross sectional methods, blood samples were collected for culture and Widal test from 502 febrile outpatients attending Mekelle hospital and Mekelle health center with similar symptoms to typhoid. Sensitivity, specificity for anti-TH and anti-TO titers using culture confirmed typhoid fever cases, and Kappa agreement between Titer and slide Widal tests were calculated. Treatment pattern of patients and antimicrobial susceptibility pattern of the blood isolates was assessed. From the 502 febrile patients, 8(1.6%) of them had culture-proven typhoid fever. However, patients who have results indicative of recent infection by O and H antigens of the Widal slide agglutination test were 343 (68.5%), with specificity and sensitivity of 33% and 100%, respectively. Over prescription of antibiotics was seen by Widal slide test for Ciprofloxacin 268 (76.1%), Amoxicillin- Clavulanic acid 9(2.6%), Amoxicillin 8(2.4%) and Chloranphenicol 8(2.4%). Tube titer positivity was seen in 23(5.3%) patients with 75% sensitivity and 95.8% specificity. Widal slide and Tube titer tests showed poor agreement for both antigens (kappa=0.02 for O) and (Kappa=0.09 for H). A single anti-TH titer of ≥ 1:160 and anti-TO titer ≥ 1:80 higher in our study showed an indication for typhoid fever infection. Drug resistance pattern of blood isolates ranges from 0-89.7% for gram positive and 0-100% for Gram negative, with an overall multi-drug resistance rate of 61.7%. Patients were wrongly diagnosed and treated for typhoid fever by Widal test. The tube titration method was relatively good but still had poor sensitivity. Blood isolates showed multi drug resistance, which may be due to the indiscriminate prescription as seen in this study. Based on our results, the slide Widal test is not helpful in the diagnosis of typhoid, hence other tests with rapid, feasible, better sensitivity and specificity are urgently needed in Ethiopia.


The effect of pH on the initiation of growth of cottage cheese spoilage bacteria.
The influence of pH on strains of Pseudomonas spp. and Enterobacter agglomerans that cause spoilage of cottage cheese varieties during storage at 7 degrees C has been investigated. In a culture medium adjusted to the required pH with HCl, 57 of 64 strains of Pseudomonas spp. grew at pH 4.8 when incubated at 7 degrees C but a very low proportion of strains grew at pH 4.7 or pH 4.6 and none at pH 4.5. At 20 degrees C some of the pseudomonads grew at pH 4.4. Three out of nine strains of E. agglomerans grew at pH 3.8 when incubated at 7 degrees C and at pH 3.6 when incubated at 20 degrees C. In cultures of E. agglomerans at controlled pH and 20 degrees C, after a lag phase the doubling time at pH 4.1 was 2 h, and at pH 7.0 was 1.4 h.


Absence of musculocutaneous nerve with variations in course and distribution of the median nerve.
Variations in the brachial plexus and its terminal branches are not uncommon. A communicating branch arising from the musculocutaneous nerve to the median nerve is a frequent variation, but complete merging of musculocutaneous nerve into the median nerve is very rare. Here, we observed variations in the origin, course and distribution of the median nerve in the left upper limb. The musculocutaneous nerve was absent. The median nerve was formed in the upper part of the arm, in front of the brachial artery. The median nerve supplied the biceps, coracobrachialis and brachialis muscles and gave the lateral cutaneous nerve of the forearm. The present report provides evidence of variation in important nerves of the anterior compartment of the arm.


Subjective quality of life of family caregivers of community living Sudanese psychiatric patients.
Reports on the quality of life (QOL) of family caregivers of psychiatric patients are uncommon. The objective of this study was to assess the subjective QOL of caregivers of stable Sudanese outpatients using the World Health Organization 26-item Quality of Life Instrument compared with a general population sample, and assess the factors associated with caregivers' QOL. Responses of caregivers of outpatients with schizophrenia (99), major affective disorders (120), and neuroses (81) were compared with 211 general population subjects. Caregivers were satisfied with the items related to the strengths of the traditional society and dissatisfied with the items related to national economic indices. Schizophrenia caregivers had lower scores than the others (P > 0.05) who scored significantly higher than general population subjects and patients. Parents had the least scores. Patients' variables were not significantly associated with caregivers' QOL. Caregivers' sociodemographic variables were significantly associated with QOL. Caregivers' QOL was predicted by their impression of patients and state of health. Schizophrenics had the least correlations with caregivers' QOL. Caregivers who are women, parents, and sick seemed relatively vulnerable and need assistance. Their areas of dissatisfaction with material circumstances should be addressed in a social welfare program. Caregivers' inner strengths, extended family supports, and positive appreciation of the patients are resources for enhancing their caregiving role.


Peptide-decorated nanocarriers penetrating the blood-brain barrier for imaging and therapy of brain diseases.
Blood-Brain Barrier (BBB) is one of the most important physiological barriers strictly restricting the substance exchange between blood and brain tissues. While the BBB protects the brain from infections and toxins and maintains brain homeostasis, it is also recognized as the main obstacle to the penetration of therapeutics and imaging agents into the brain. Due to high specificity and affinity, peptides are frequently exploited to decorate nanocarriers across the BBB for diagnosis and/or therapy purposes. However, there are still some challenges that restrict their clinical application, such as stability, safety and immunocompatibility. In this review, we summarize the biological and pathophysiological characteristics of the BBB, strategies across the BBB, and recent progress on peptide decorated nanocarriers for brain diseases diagnosis and therapy. The challenges and opportunities for their translation are also discussed.


High-dose epirubicin in chemotherapy refractory non-seminomatous germ cell cancer: a phase II study. EORTC Genito-Urinary Tract Cancer Co-operative Group. EORTC Early Clinical Trials Group.
Eighteen patients with progressive disseminated, platinum-resistant germ cell tumors were treated with epirubicin 135 mg/m2, every 3 weeks. One patient had stable disease, 17 developed progression. Myelosuppression was dose-limiting. One patient died of neutropenic septicemia. High-dose epirubicin is not active against platinum-resistant germ cell cancer.


Endovascular treatment of a ruptured internal thoracic artery pseudoaneurysm presenting as a massive hemothorax in a patient with type I neurofibromatosis.
We report a case of acute hemothorax caused by a left internal thoracic artery pseudoaneurysm rupture in a patient with neurofibromatosis type I, which was successfully treated with endovascular coil embolization.


Treatment of recurrent gynecologic malignancies with iodine-125 permanent interstitial irradiation.
To analyze the outcome of permanent 125I interstitial radiotherapy for unresectable retroperitoneal recurrences of gynecologic malignancies. A retrospective review of 20 patients treated between 1979 and 1993 was performed to evaluate survival and morbidity associated with the interstitial 125I technique. Nineteen tumors were located on the lateral pelvic wall and one in the para-aortic region. Eight patients, not previously irradiated, received external beam radiotherapy (EBRT) along with 125I interstitial implants placed at the time of celiotomy. Nineteen (95%) are dead of disease at 1-69 months of follow-up. The median survival was 7.7 months for patients treated with 125I alone and 25.4 months for those treated with both 125I and EBRT. One patient is alive without evidence of disease 69 months after 125I implantation. Fistulas, bowel obstructions, and fatal complications occurred only among patients previously irradiated. When used in a previously irradiated field, 125I interstitial radiotherapy has major morbidity and is unlikely to be associated with cure or long-term survival. In radiotherapy-naive patients with unresectable isolated recurrent gynecologic malignancies, 125I implants and EBRT are feasible and occasionally may contribute to long-term disease-free survival.


Risk assessment tools for QT prolonging pharmacotherapy in older adults: a systematic review.
Many drugs are associated with the risk of QT prolongation and torsades de pointes (TdP), and different risk assessment tools (RATs) are developed to help clinicians to manage related risk. The aim of this systematic review was to summarize the evidence of different RATs for QT prolonging pharmacotherapy. A systematic review was conducted using PubMed and Scopus databases. Studies concerning risk assessment tools for QT prolonging pharmacotherapy, including older adults, were included. Screening and selection of the studies, data extraction, and risk of bias assessment were undertaken. A total of 21 studies were included, involving different risk assessment tools. Most commonly used tools were risk scores (n = 9), computerized physician order entry systems (n = 3), and clinical decision support systems (n = 6). The tools were developed mainly for physicians and pharmacists. Risk scores included a high number of risk factors, both pharmacological and non-pharmacological, for QT prolongation and TdP. The inclusion of patients' risk factors in computerized physician order entry and clinical decision support systems varied. Most of the risk assessment tools for QT prolonging pharmacotherapy give a comprehensive overview of patient-specific risks of QT prolongation and TdP and reduce modifiable risk factors and actual events. The risk assessment tools could be better adapted to different health information systems to help in clinical decision-making. Further studies on clinical validation of risk assessment tools with randomized controlled trials are needed.


Osmotic shock fluids from salmonella R-mutants. Chemical composition and protective capacity against S. typhimurium infection in mice.
Salmonella R-mutants of different chemotype were subjected to osmotic shock treatment according to the method of Willis et al. (18). Chemical composition (protein, LPS, palmitic acid and nucleic acids) as well as the polypeptide patterns of the shock fluid and hypertonic fluid (in which the cells were suspended before shock treatment) were determined and compared with material extracted by urea treatment carried out to get protein from the cell surface. The results indicate that even components from the cell surface have been released by shock treatment. All the extracts mentioned above showed protective activity in mouse against infection.


Lung transplantation in patients with cystic fibrosis.
Cystic fibrosis (CF) an autosomal recessive genetic disorder, affects many organs. The great majority of deaths occur due to respiratory failure after many years of chronic pulmonary infection. Despite recent progress in early detection by studies of genetic mutations and better understanding to treat nutritional and infectious states, lung transplantation is the CF treatment for most advanced cases. According to the International Society for Heart and Lung Transplantation (ISHLT) data, CF is the third most common reason for lung transplantation (16.8%) showing the best survival rate (60% at 5 years). We have described our experience in lung transplantation of CF patients between January 2000 and December 2011, reviewing medical charts of these patients were for gender, age, body mass index (BMI), comorbidities, disease duration, previous sputum gram stain, ischemic time, incidence of severe primary graft dysfunction (PGD Grade 3), intensive care unit (ICU) length of stay, and Kaplan-Meier survival. Among 150 lung transplantation, the 30 CF patients (20%) represented the second most common cause. The average age was 27.4 ± 9.2 years, with a slight predominance of males (n = 16; 53.3%). The average BMI was 18.9 ± 2.6. Most patients (60%) had pancreatic exocrine dysfunction. Also, 83.3% of patients showed a positive sputum culture for Pseudomonas, while Burkholderia cepacia was identified in only 4 patients (13.3%). The average time of the disease was 20.8 ± 9.7 years. All transplantation were bilateral with an average ischemic time of 472 ± 98.3 minutes and ICU length of stay of 9.9 ± 6.3 days. The survival rates at 1 and 5 years were 92% and 77%, respectively, corresponding to the best outcomes among underlying diseases, comparable with other worldwide series and better than the ISHLT reports. CF, the second most common cause for lung transplantation among our cases, showed the best survival rate among all causes. Our survival rate was comparable with other reports.


Involvement of 5-HT2 receptors in the LSD- and L-5-HTP-induced suppression of lordotic behavior in the female rat.
Copulatory behavior in the ovariectomized rat, the lordotic response (L.R.), was induced by estrogen followed by progesterone. L.R. is inhibited by lysergic acid diethylamide (LSD) (greater than or equal to 0.05 mg/kg) and by Levo-5-hydroxytryptophan (L-5-HTP) (greater than or equal to 2.5 mg/kg). The effects of the putative 5-HT antagonists lisuride, metergoline, methysergide, mianserin, cinanserin, cyproheptadine, pirenperone and altanserin on the LSD-induced inhibition of L.R. were tested. Lisuride, metergoline, methysergide and mianserin were found to have no LSD-blocking effect. In contrast, cinanserin, cyproheptadine and pirenperone acted antagonistically to LSD, within a critical dose range. The selective 5-hydroxytryptamine2 (5-HT2) receptor antagonist altanserin effectively prevented the LSD-induced inhibition of L.R., and the doses required (0.05-0.20 mg/kg) indicated a comparatively high antagonistic potency. In addition altanserin (0.2 mg/kg) effectively prevented the lordosis inhibitory effect induced by L-5-HTP (2.5 mg/kg), after pretreatment with pargyline and RO4-4602. It is suggested that the suppression of copulatory behavior caused by LSD and L-5-HTP is mediated by 5-HT2 receptors.


Finding differentially expressed genes in high dimensional data: Rank based test statistic via a distance measure.
We present a rank-based test statistic for the identification of differentially expressed genes using a distance measure. The proposed test statistic is highly robust against extreme values and does not assume the distribution of parent population. Simulation studies show that the proposed test is more powerful than some of the commonly used methods, such as paired t-test, Wilcoxon signed rank test, and significance analysis of microarray (SAM) under certain non-normal distributions. The asymptotic distribution of the test statistic, and the p-value function are discussed. The application of proposed method is shown using a real-life data set.


Simultaneous biosuccinic production and biogas upgrading: Exploring the potential of sugar-based confectionery waste within a biorefinery concept.
The imminent need for fossil fuel independence in EU countries has led to an increased development of organic waste valorisation technologies for the production of biomethane and chemical building blocks, such as bio-succinic acid (SA). In this work, the potential of two confectionery waste, in the form of wastewater (SCWW) or a side-stream rejection (SSCW), as inexpensive carbon sources for simultaneous SA production and biogas upgrading was evaluated for the first time. Both substrates were tested batchwise with evolved Actinobacillus succinogenes cultures at different nutrient conditions, SSCW at 100 g L-1 resulting in the highest titres/productivities (∼80 g L-1 and 1.3 g L-1h-1, respectively). Then, simultaneous biogas upgrading under continuous gas feeding was studied at bioreactor-scale, higher gas residence times and pressurization leading to desirable biomethane purities (>98%). The research here conducted is crucial for the cost-effectiveness and scale-up of the technology along this new waste-based biorefinery concept.


Absolute coronary artery calcium score is the best predictor of non-calcified plaque involvement in patients with low calcium scores (1-100).
We sought to identify the predictors of non-calcified plaque (NCP) burden in patients with low coronary artery calcium (CAC) scores of 1-100. We studied 920 consecutive patients clinically referred for coronary CT angiography (CCTA) with concomitant CAC scoring. The 276 patients with CAC 1-100 were divided into four groups based on the CAC score: CAC = 0, 1-10, 11-50, and 51-100. Univariate and multivariate linear regression analyses were performed for the demographic, risk factor, and CAC score predictors of number of coronary segments with NCP. Mean age was 55 ± 11 years and 56% were women. Demographics and risk factors failed to identify NCP involvement in univariate models. The lone predictor of NCP burden was the absolute CAC score, which was persistently associated with NCP in multivariable models (CAC 51-100 vs. CAC 1-10, β-coefficient 0.35, p = 0.03). Absolute CAC score is the lone robust predictor of NCP burden when CAC is 1-100. Risk within this mild coronary calcification group is likely heterogeneous, driven by the absolute CAC score.


Masticatory Myofascial Pain Syndrome: Implications for Endodontists.
Masticatory myofascial pain syndrome can present similarly to other dental conditions in odontogenetic structures. Endodontists should be familiar with the symptomology and pathophysiology of masticatory myofascial pain syndrome to avoid misdiagnosis, incorrect treatment, and medicolegal repercussions. The aim of this review was to provide a foundational summary for endodontists to identify and correctly manage masticatory myofascial pain syndrome. A narrative review of the literature was performed through a MEDLINE search and a hand search of the major myofascial pain textbooks. Masticatory myofascial pain syndrome is a musculoligamentous syndrome that can present similarly to odontogenic pain or refer pain to the eyebrows, ears, temporomandibular joints, maxillary sinus, tongue, and hard palate. Currently, the most comprehensive pathophysiology theory describing masticatory myofascial pain syndrome is the expanded integrated hypothesis. The most widely accepted diagnostic guidelines for masticatory myofascial pain syndrome are the Diagnostic Criteria for Temporomandibular Disorders; however, their diagnostic capability is limited. There is no hierarchy of treatment methods because each patient requires a tailored and multidisciplinary management aimed at regaining the muscle's range of motion, deactivating the myofascial trigger points, and maintaining pain relief. The pain patterns for masticatory myofascial pain syndrome are well-known; however, there is a lack of consensus on the most proper method of trigger point diagnosis or pain quantification. The diagnostic strategies for masticatory myofascial pain syndrome vary, and the diagnostic aids are not well developed.


Frequency and distribution of cyanogenic glycosides in Eucalyptus L'Hérit.
In this study approximately 420 of the described species of Eucalyptus were examined for cyanogenesis. Our work has identified an additional 18 cyanogenic species, 12 from living tissues and a further six from herbarium samples. This brings the total of known cyanogenic species to 23, representing approximately 4% of the genus. The taxonomic distribution of the species within the genus is restricted to the subgenus Symphyomyrtus, with only two exceptions. Within Symphyomyrtus, the species are in three closely related sections. The cyanogenic glycoside was found to be predominantly prunasin (1) in the 11 species where this was examined. We conclude that cyanogenesis is plesiomorphic in Symphyomyrtus (i.e. a common basal trait) but has probably arisen independently in the other two subgenera, consistent with recent phylogenetic treatments of the genus. The results of this study have important implications for the selection of trees for plantations to support wildlife, and to preserve genetic diversity.


Precision spectroscopy of hydrogen and femtosecond laser frequency combs.
Precision spectroscopy of the simple hydrogen atom has inspired dramatic advances in optical frequency metrology: femtosecond laser optical frequency comb synthesizers have revolutionized the precise measurement of optical frequencies, and they provide a reliable clock mechanism for optical atomic clocks. Precision spectroscopy of the hydrogen 1S-2S two-photon resonance has reached an accuracy of 1.4 parts in 10(14), and considerable future improvements are envisioned. Such laboratory experiments are setting new limits for possible slow variations of the fine structure constant alpha and the magnetic moment of the caesium nucleus mu(Cs) in units of the Bohr magneton mu(B).


Epoxycholesterols in secretions and tissues of normal, benign, and cancerous human prostate glands.
Extracts of prostatic secretions taken from 25 control subjects, twenty-three to seventy-five years of age, were analyzed by gas-liquid chromatography (GLC) for cholesterol and possible epoxycholesterol content. Only subjects fifty-three years or older exhibited any signs of prostatic enlargement. Whereas cholesterol (893 +/- 133 micrograms/ml) was found in all prostatic secretions, the carcinogenic epoxycholesterols (22.6 +/- 3.3 micrograms/ml) were detected only in one third of the specimens examined. Prostatic secretion collected from 29 surgical patients prior to primary (20) and secondary (9) prostatectomies revealed cholesterol contents of 1,182 +/- 148 and 1,134 +/- 157 micrograms/ml, respectively. The epoxycholesterols were essentially present at concentrations of 33.7 +/- 7.9 and 24.0 +/- 10.3 micrograms/ml, respectively. Tissue extracts of the different prostatic lobes taken from 40 surgical BPH patients at the time of primary (26) and secondary (14) prostatectomy were examined by capillary GLC. Of these patients 8 had prostatic carcinoma. The cholesterol content of all tissues was essentially double that of normal prostates. The epoxycholesterols were present in all tissues. The mean cholesterol 5 alpha, 6 alpha-epoxide and cholesterol 5 beta, 6 beta-epoxide contents of all tissue were 120 +/- 23.4 and 9.9 +/- 5.2 micrograms/Gm dry tissue, respectively. There were no apparent differences beteeen the lobes nor between BPH and cancers. No epoxycholesterol could be detected in 8 seminal vesicles obtained at autopsy.


[Canine tuberculosis and its importance in public health].
The present paper describes tuberculosis in a family whose dog also presented the disease. The importance of animal epidemiological investigation in cases of tuberculosis in man is discussed.


Long-term electrode implantation for recording cochlear electrical activity in guinea pigs.
Comparative measurements of the cochlear electrical activity over prolonged periods require long-term implantation of electrodes. During this time, changes in the electrode recording ability and/or impairment of the sound-conducting system, could erroneously be attributed to the experiment. To avoid this risk, an easy and reliable technique is described. The procedure uses the Fallopian canal as a route by which to approach the cochlear potentials' generators, while leaving the middle ear untouched.


Global profiling of Streptococcus pneumoniae gene expression at different growth temperatures.
Streptococcus pneumoniae is a common commensal of the upper respiratory tract of healthy humans and is an important pathogen in young children, immunocompromised adults, and the elderly. To better understand the strategies employed by this bacterial species in adapting to conditions present at different infection sites in the host, global transcription profiling was used to study gene expression at different growth temperatures: 21, 29, 33, 37, and 40 degrees C. Here, we found that 658 genes (29%) out of 1717 genes were differently expressed (>or=1.5-fold change) in at least one growth temperature relative to 37 degrees C. The percentages of genes whose expression was altered in each growth temperature, respectively, were: 21 degrees C: 53% upward arrow, 47% downward arrow; 29 degrees C: 44% upward arrow, 56% downward arrow; 33 degrees C: 27% upward arrow, 73% downward arrow and 40 degrees C: 44% upward arrow, 56% downward arrow. Hierarchical clustering (HC) of the temperature regulated genes resulted in four clusters, namely A-D of differently expressed genes grouped by bacterial growth temperature. Cluster A represented 81 genes reflecting enhanced expression at 33 degrees C. Cluster B included 260 genes whose expression increased with growth temperature. Cluster C had 28 genes with 68% showing enhanced expression at 29 degrees C while cluster D had 289 genes with 74% genes showing enhanced expression at 21 degrees C relative to 37 degrees C. Principal component (PC) analysis also divided differentially expressed genes into four groups and was highly correlated with HC, suggesting that temperature regulated expression is not random but coordinated. Overall, these results indicated substantial reprogramming of transcription in response to growth temperature. Functional characterization of differential gene expression at different temperatures provides further information on the molecular mechanism(s) that allows S. pneumoniae to adapt to various host environments.


Craving mediates the association between momentary pain and illicit opioid use during treatment for opioid-use disorder: an ecological momentary assessment study.
To assess the role of momentary pain on opioid craving and illicit opioid use among individuals receiving opioid agonist treatment. Observational study using ecological momentary assessment. The National Institute of Drug Abuse Intramural Research Program in the United States. Fifty-six adults who qualified for opioid agonist treatment. Participants completed randomly prompted assessments of pain severity, stress, negative mood, opioid craving and illicit opioid use for a mean of 66 days [standard deviation (SD) = 27]. Urine samples were collected two to three times/week throughout. Almost 70% of participants reported moderate average pain severity in the past 24 hours at intake and 35% of participants reported chronic pain. There were no significant differences in percent of opioid-positive urine samples (P = 0.73) and average level of opioid craving during the study period (P = 0.91) among opioid agonist treatment only patients versus opioid agonist treatment patients with chronic pain. However, momentary pain severity significantly predicted concurrent opioid craving [B = 0.02, 95% confidence interval (CI) = 0.01, 0.04], over and above stress and negative mood. Momentary opioid craving, in turn, significantly predicted illicit opioid use that was assessed in the next moment [odds ratio (OR) = 1.72, 95% CI = 1.12, 2.64), while controlling for autocorrelation and the effects of pain, negative mood and stress. Momentary opioid craving significantly mediated the prospective association between momentary pain and illicit opioid use (95% CI = 0.003, 0.032). Exploratory analysis revealed that momentary pain severity also significantly moderated the momentary association between stress and opioid craving (B = 0.02, 95% CI = 0.00, 0.04), such that when momentary pain severity increased, the association between the two intensified. Among people receiving opioid agonist treatment, momentary pain appears to be indirectly associated with illicit opioid use via momentary opioid craving.


Gemin5-dependent RNA association with polysomes enables selective translation of ribosomal and histone mRNAs.
Selective translation allows to orchestrate the expression of specific proteins in response to different signals through the concerted action of cis-acting elements and RNA-binding proteins (RBPs). Gemin5 is a ubiquitous RBP involved in snRNP assembly. In addition, Gemin5 regulates translation of different mRNAs through apparently opposite mechanisms of action. Here, we investigated the differential function of Gemin5 in translation by identifying at a genome-wide scale the mRNAs associated with polysomes. Among the mRNAs showing Gemin5-dependent enrichment in polysomal fractions, we identified a selective enhancement of specific transcripts. Comparison of the targets previously identified by CLIP methodologies with the polysome-associated transcripts revealed that only a fraction of the targets was enriched in polysomes. Two different subsets of these mRNAs carry unique cis-acting regulatory elements, the 5' terminal oligopyrimidine tracts (5'TOP) and the histone stem-loop (hSL) structure at the 3' end, respectively, encoding ribosomal proteins and histones. RNA-immunoprecipitation (RIP) showed that ribosomal and histone mRNAs coprecipitate with Gemin5. Furthermore, disruption of the TOP motif impaired Gemin5-RNA interaction, and functional analysis showed that Gemin5 stimulates translation of mRNA reporters bearing an intact TOP motif. Likewise, Gemin5 enhanced hSL-dependent mRNA translation. Thus, Gemin5 promotes polysome association of only a subset of its targets, and as a consequence, it favors translation of the ribosomal and the histone mRNAs. Together, the results presented here unveil Gemin5 as a novel translation regulator of mRNA subsets encoding proteins involved in fundamental cellular processes.


Correlating EEG and IQ: a new look at an old problem using computerized EEG parameters.
Explorations of the relationship between EEG activity and scores of tests of intelligence have a long history. Results have been rather discrepant and several explanations can be offered for this. Almost all previous studies relied on parameters derived from a visual rather than a computerized analysis of the EEG. Here broad band spectral parameters were mainly used, and in addition the frequency of the dominant peak (at Pz, O1 and O2) between 6.5 and 14.0 Hz. All EEG parameters were standardized for age, as were tests of intelligence. Correlations of EEG with IQ were computed separately for a group of normal and a group of mildly retarded children. As postulated in advance, correlations were substantially higher for the retarded groups. Even more remarkable than the size of the correlations found was their pattern, associated with an interesting interpretation: the sign of the larger correlations was such that children developmentally more advanced in their EEG parameters had on the average higher IQ scores. Moreover, correlations were large for those frequency bands, and to a lesser degree for those derivations where we found a high developmental relevance in a previous investigation for the age range considered. Some disappointing or even discrepant results in earlier studies can be explained in the light of the results given here.


Nucleic acid interaction with VERO cells. A temperature barrier in the interaction pattern.
The interaction of VERO cell monolayers with spin (nitroxide)-(labeled polynucleotides (1(N)n) was examined by electron spin resonance (ESR) spectroscopy at various temperatures. Nitroxide labels covalently linked to (A)n, (dUfl)n, (U)n and (A)n . (U)n were used to monitor the interaction. The VERO cells were grown on small quartz plates with a cell viability of 95% or better and then used directly for the ESR studies. The ESR results indicated that the interaction between VERO cells and spin-labeled nucleic acids is temperature dependent. No temperature dependence was found when VERO cells were in contact with nitroxide radicals which were free in solution or covalently bound to Sepharose 4B. The temperature dependence established with nitroxide-labeled nucleic acids indicates that a temperature barrier must exist between 20 and 26 degrees C for the interaction between nucleic acids and VERO cells; namely, at 26 degrees C or above spin-labeled nucleic acids interact significantly with a VERO cell surface; whereas, at 20 degrees C the ESR signal reports no interaction. It is concluded that a temperature-dependent phase transition of membrane components or cell surface products active at 26 degrees C or above play a key role in the nucleic acid cell surface interaction process.


Tolerability of N-chlorotaurine in chronic rhinosinusitis applied via yamik catheter.
A rational approach in the treatment of chronic rhinosinusitis (CRS) is the intranasal application of antiseptic agents, due to the pathogenetic role of bacteria and fungi. N-Chlorotaurine (NCT), a mild endogenous oxidant with broad-spectrum antimicrobial activity, has been tested for the first time in CRS. This one-arm phase IIa clinical study is the first step in the clinical development of this promising substance for local therapy of CRS. The nasal and paranasal cavities of 12 patients were rinsed with 10-20 ml of 1% aqueous NCT solution, applied via a novel catheter system (YAMIK). Treatment consisted of three lavages per week for 4 weeks. NCT caused neither alterations of the mucosa nor burning pain during application. Nevertheless, the insertion of the catheter, the insufflation of the posterior cuff and the overpressure inside the sinuses after infiltration led to moderate pain in some patients. Mucosal swelling decreased in all subjects, nasal breathing could be improved in nine patients and impaired olfaction in seven. Polyps did not disappear within the 1-month period of the study. The good tolerability and possible beneficial effects of NCT encourage its further investigation in CRS. Despite some limitations the YAMIK catheter proved to be a convenient and safe device for rinsing the nasal and paranasal sinuses.


Identification and genomic features of halotolerant extended-spectrum-β-lactamase (CTX-M)-producing Escherichia coli in urban-impacted coastal waters, Southeast Brazil.
We report the occurrence and genomic analysis of extended-spectrum β-lactamase (CTX-M)-producing Escherichia coli in anthropogenically polluted coastal waters of Southeast Brazil. E. coli strains belonging to sequence types (STs) ST10, ST38, ST155 and ST1284 exhibited a wide resistome, with genes conferring resistance to medically relevant antimicrobials and heavy metals, and a halophilic behavior (tolerance to 9-10% NaCl). These findings suggest a heavy contamination in this area by critical priority bacteria adapted to marine environments, which might have negative impacts on human and ocean health.


Changes in the activity of GAD in the basal ganglia of the rat after striatal dopaminergic denervation.
The aim of this experiment was to study the effect of a unilateral lesion of the dopamine-containing nigro-striatal pathway, on the activity of glutamic acid decarboxilase (GAD) in different structures at two survival times: 4 and 8 weeks. The structures studied were the striatum and its output target areas, globus pallidus, entopeduncular nucleus and substantia nigra. Four weeks after the lesion, GAD activity was increased in the ipsilateral striatum, globus pallidus and substantia nigra. This effect was reversed at 8 weeks, when a decrease in enzyme activity was observed. These time related changes in enzyme activity reveal the presence of a physiological compensatory process.


Spousal resemblance in the Canadian population: implications for the obesity epidemic.
To determine the extent of the spousal resemblance for adiposity and leanness in the Canadian population. Cross-sectional population survey. The sample comprised parents and offspring from 1341 families (n=4023) of the Canada Fitness Survey. Indicators of adiposity included the body mass index (BMI) and the sum of five skinfolds (SF5). Both offspring and parents were ranked by their BMI and SF5 percentile position in the population using the entire Canada Fitness Survey database (n=15 818). Pearson correlations indicated significant spousal resemblance for both BMI (r=0.14; P<0.0001) and SF5 (r=0.13; P<0.0001). However, the magnitude of the spousal correlations varied by the adiposity status of the offspring, with spousal correlations tending to be stronger in parents of lean or obese children and lower among parents of 'average' children. Bivariate histograms indicated that among lean (<or=5th percentile) and obese offspring (>or=95th percentile), the parental pairs tended to cluster among the lower and higher percentiles of adiposity, respectively. There are spousal similarities in adiposity, particularly among parents of lean or obese offspring in the Canadian population. The degree to which these similarities are due to a loading of spouses with genes predisposing to obesity or a shared household environment cannot be determined from the present study. However, these results are compatible with the notion that genes and mutations predisposing to obesity are more prevalent among obese parents while those for pronounced leanness are more prevalent among lean parents.


The association of long-term ambient fine particulate matter exposure with blood pressure among Chinese adults.
Previous studies indicated that long-term exposure to high level of fine particulate matter (PM2.5) was associated with elevated blood pressure (BP) and hypertension, but most of them were conducted in high-income countries with low PM2.5 level. Therefore, we aimed to evaluate the adverse impacts of long-term exposure to PM2.5 on BP and hypertension in China with high concentration. A total of 99,084 adults aged ≥18 years old were included from three cohorts among the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China. PM2.5 concentrations during 2000-2015 at 1 × 1 km spatial resolution were evaluated using satellite-based spatiotemporal models. Generalized estimating equation was applied to assess the impact of three-year average PM2.5 concentrations on BP level and hypertension. We also examined whether health status and lifestyles modified the effects of PM2.5 on BP and hypertension. Generally, high concentration of PM2.5 was associated with increased BP level and higher risk of hypertension. With each 10 μg/m3 increment in PM2.5 concentration, systolic BP (SBP) and diastolic BP (DBP) increased by 1.67 [95% confidence interval (CI): 1.48, 1.86] mmHg and 0.45 (95% CI: 0.35, 0.56) mmHg, and the prevalence of hypertension increased by 29% [odds ratio (OR): 1.29, 95% CI: 1.26, 1.32]. In comparison with the first quartile of PM2.5 concentration, SBP, DBP and prevalence of hypertension in the fourth quartile were increased by 8.26 (95% CI: 7.73, 8.80) mmHg, 2.85 (95% CI: 2.55, 3.15) mmHg, and 133% (OR: 2.33, 95% CI: 2.21, 2.47), respectively, in the fully adjusted model. However, the relationships of PM2.5 with BP might be non-linear, as BP level started to decline when PM2.5 exceeded 75 μg/m3. In conclusion, long-term PM2.5 exposure could elevate BP level and prevalence of hypertension. People living in high-polluted areas should strengthen their awareness of prevention.


Study of the elution mechanism of sodium aryl sulfonates on bare silica and a cyano bonded phase with methanol-modified carbon dioxide containing an ionic additive.
The elution mechanism of sodium sulfonates on both Deltabond cyanopropyl and bare silica stationary phases with an isocratic mobile phase composed of methanol-modified CO2 wherein an ammonium salt additive was dissolved in the methanol has been studied. The presence of the additive was crucial concerning elution of the sulfonate salts. Solid state 29silicon nuclear magnetic resonance spectroscopy provided some insight concerning the interaction of the mobile phase additive with the silica-based stationary phase. Computational calculations concerning the charge distribution on various ammonium salts were performed in an effort to explain the elution behavior. Ammonium ions are believed to deactivate available silanol sites on both phases. In addition, ammonium ion is speculated to interact with the cyano groups on the bonded phase. For concentrations of additive greater than 2 mM, stationary phase coverage of ammonium ion is anticipated to exceed one monolayer for both bare and bonded silica. The acetate counter-ion is thought to facilitate elution of the anionic sulfonates from the positively charged stationary phase in a pseudo ion exchange mechanism.


Plasmodium falciparum: invasion and development in highly parasitized cultures.
We report that synchronized cultures of Plasmodium falciparum with up to 40% parasitized cells can be obtained with the use of low, red blood cell suspensions and only daily replacement of culture medium. These cultures contained not only a reduced proportion of uninfected red cells but also a population of cells with brief and equal time of exposure to culture conditions. Such high parasitemias are desirable for studies of ring-staged parasites (for which enrichment techniques are not available) and late-staged parasites when the manipulations for enrichment are inappropriate or unsuccessful.


Compressing data volume of left ventricular cineangiograms.
In this paper a method of compressing data volume for left ventricular cineangiograms is proposed. This method enables digital-optical discs to store the cineangiograms with an equivalent recording density to that of HDTV VTR's while preserving the quality of the original image. The data volume of the cineangiograms is compressed by approximating function and storing its coefficients. With this method, each cineangiogram frame is first decomposed into three regions: the inner part, the inner wall, and the background (using a statistical method previously reported by the authors). Each region is then compressed by means of a difference operation and an adaptive approximation with smooth functions. Performance is tested on 20 cases using actual cineangiograms. The specifications were verified for a spatial resolution of 1000 TV lines, a dynamic range of 60 dB, an SNR of 40 dB [pp/rms], volume compression to 7% of the original volume, and 0.19 [second/frame] for decoding on a 1.7 MFLOPS computer.


A unifying view on extended phase graphs and Bloch simulations for quantitative MRI.
Quantitative MRI methods and learning-based algorithms require exact forward simulations. One critical factor to correctly describe magnetization dynamics is the effect of slice-selective RF pulses. While contemporary simulation techniques correctly capture their influence, they only provide final magnetization distributions, require to be run for each parameter set separately, and make it hard to derive general theoretical conclusions and to generate a fundamental understanding of echo formation in the presence of slice-profile effects. This work aims to provide a mathematically exact framework, which is equally intuitive as extended phase graphs (EPGs), but also considers slice-profiles through their natural spatial representation. We show, through an analytical, hybrid Bloch-EPG formalism, that the spatially-resolved EPG approach allows to exactly predict the signal dependency on off-resonance, spoiling moment, microscopic dephasing, and echo time. We also demonstrate that our formalism allows to use the same phase graph to simulate both gradient-spoiled and balanced SSFP-based MR sequences. We present a derivation of the formalism and identify the connection to existing methods, i.e. slice-selective Bloch, slice-selective EPG, and the partitioned EPG. As a use case, the proposed hybrid Bloch-EPG framework is applied to MR Fingerprinting.


Microaerophilic Symmetric Reductive Cleavage of Reactive Azo Dye-Remazole Brilliant Violet 5R by Consortium VIE6: Community Synergism.
The textile-dyeing industry is rated as one of the foremost industrial sectors that explodes large amount of pollutants to the environment. Reactive azo dye degradation, being a major constituent of these pollutants and perilous material, has been constantly receiving scientific attention. In textile industry, use of Remazole Brilliant Violet 5R (RBV5R) as reactive azo dyes is more frequent. Highly competent, RBV5R-degrading bacterial consortium VIE6 was developed from the soil of the Vatva Industrial Estate, Gujarat, India. Consortium VIE6 comprised of five bacterial strains Bacillus sp. DMB1, Staphylococcus sp. DMB2, Escherichia sp. DMB3, Enterococcus sp. DMB4, and Pseudomonas sp. DMB5. These strains convened a better decolorization efficiency between 200 and 1000 mg/L of dye concentration and were much stable at pH 6.5, 37 °C. Azoreductase, laccase, and lignin peroxidase activities of consortium showed significant variation throughout the degradation process indicating the different metabolic capabilities of the existing microflora. The community interactions and synergism were shown to facilitate the biotransformation of RBV5R by combination of various electron donors. Voltammograms revealed the variations in electron discharge properties which coincide with the dynamics of community derived using qPCR assays. The variation in catabolic capabilities of the individual strains was observed during active metabolism of RBV5R degradation pertaining to the aerobic and facultative functions.


The epidemiology of stomach cancer in Bavaria.
Stomach cancer represents an important cause of death in the Federal Republic of Germany, the regional analysis of mortality rates showing that the rates in Bavaria lay significantly above the national average during the years 1952 till 1978. Within this Federal State the mortality again is not uniform but regions in the Northeast with high rates are distinguishable from low mortality in the Southwest. Furthermore, the analysis by age and birth cohorts shows a decrease of mortality from stomach cancer with later years of birth. The considerable differences in consecutive birth cohorts, given the regional patterns, may indicate a varying exposure to etiological factors, most likely to be sought in the early life of the later cancer victims. In an attempt to clarify the reasons for these regional particularities a case-control study is designed to investigate, among other factors, the etiological relevance of nutritional habits. The possible influence of competing causes of death is discussed.


Three-dimensional observation of the mouse embryo by micro-computed tomography: Meckel's cartilage, otocyst, and/or muscle of tongue.
Three-dimensional observation during embryogenesis is possible with micro-computed tomography, but there are no observations of organ size. In this paper, three examples of three-dimensional observation of organs by micro-CT are tried. At 13.0 days post-coitum, mouse embryos were fixed in 4% paraformaldehyde for 24 h and stained enbloc by osmium tetroxide overnight. The embryos were then embedded in paraffin using standard methods for 24 h. Specimens were analyzed by micro-computed tomography and image processing was performed. The entire Meckel's cartilage and its relation in the mandible, as well as the complex structure of the otocyst, are easily visualized. Although it is difficult to extract detailed structures of the tongue muscles, it is possible to identify the inner and external tongue muscles. Relation among the organs and other are easily visualized. Three-dimensional observation by micro-computed tomography is an important technology for visualization of embryogenesis and could be used in organ culture.


Characterization and mass balance of dioxin from a large-scale municipal solid waste incinerator in China.
The input and output samples from existing large-scale municipal solid waste incinerator (MSWI) were collected and analyzed for polychlorinated dibenzo-р-dioxins and dibenzofurans (PCDD/Fs) in this study, aiming to evaluate PCDD/F characteristic and the corresponding mass balance through the whole system. The grate-type MSWI is equipped with semi-dry scrubber, activated carbon injection, and bag filter as air pollutant control devices (APCDs). Results showed that on the output side, the stack gas, bottom ash and fly ash presented their mean dioxin levels of 0.078 ng I-TEQ/Nm(3), 12.94 ng I-TEQ/kg and 858 ng I-TEQ/kg, respectively, and showed large similarities in congener profiles. Instead, on the input side, the municipal solid waste (MSW) presented a mean dioxin level of 15.56 ng I-TEQ/kg and a remarkable difference in congener profiles compared with those of the output. The dioxin mass balance demonstrated that the annual dioxin input value was around 5.38 g I-TEQ/yr, lower than the total output value (7.62 g I-TEQ/yr), signifying a positive dioxin balance of about 2.25 g I-TEQ/yr.


Pentoxifylline reduces inflammation and prevents myocardial perfusion derangements in experimental chronic Chagas' cardiomyopathy.
Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters. We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 ± 1.6 to 9.4 ± 9.7%), but not in CH + PTX (1.9 ± 3.0% to 2.7 ± 2.7%) that exhibited MPD area similar to CO (0.0 ± 0.0% to 0.0 ± 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 ± 88.3 cell/mm2), as compared to CH + SLN (515.1 ± 133.0 cell/mm2), but larger than CO (193.0 ± 25.7 cell/mm2). The fibrosis and TNF-α expression was higher in both infected groups. The prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC.


Yeast two-hybrid detection systems that are highly sensitive to a certain kind of endocrine disruptors.
We tested the effects of several combinations of bait and fish components of the yeast two-hybrid detection system for estrogenic activity. A combination of the full-length human estrogen receptor alpha with the nuclear receptor-binding domain of co-activator steroid receptor co-activator-1 (SRC-1) or transcriptional intermediate factor-2 (TIF-2) was most effective for estrogen-dependent induction of the chromosome-integrated UAS(GAL)-CYC1(p)-lacZ reporter construct among the two-hybrid systems so far tested.


Mechanisms of oral absorption improvement for insoluble drugs by the combination of phospholipid complex and SNEDDS.
In the present study, a water insoluble drug named silybin was encapsulated into self-nanoemulsifying drug delivery system (SNEDDS) following the preparation of silybin-phospholipid complex (SB-PC), then several methods were carried out to characterize SB-PC-SNEDDS and elucidate its mechanisms to improve the oral absorption of SB. Using a dynamic in vitro digestion model, the lipolysis of SB-PC-SNEDDS was proved to be mainly related with the property of its lipid excipients. SB-PC-SNEDDS could significantly enhance the transport of SB across Caco-2 cells, which may partly attribute to the increased cell membrane fluidity and the loss of tight junction according to the analysis results of fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and tight junction protein (ZO-1). The result of in situ perfusion showed the intestinal absorption of SB from high to low was SB-PC-SNEDDS, SB-PC, and SB. The extent of lymphatic transport of SB-PC and SB-PC-SNEDDS via the mesenteric duct was 12.2 and 22.7 folds of that of SB, respectively. In the lymph duct cannulated rats, the relative bioavailability (Fr) of SB-PC and SB-PC-SEDDS compared to SB was 1265.9% and 1802.5%, respectively. All the above results provided mechanistic support for oral absorption improvement of water insoluble drugs by the combination of PC and SNEDDS.


Natural history of atherosclerotic and fibrous renal artery disease: clinical implications.
Atherosclerotic renal artery disease and the fibrous renal artery diseases are described with respect to their radiographic and clinical characteristics. In a retrospective review, serial renal arteriograms of 85 patients with atherosclerotic renal artery disease and 66 patients with the medial fibroplasia type of fibrous renal artery disease were analyzed to characterize their natural history. Atherosclerotic renovascular disease progressed in 37 patients (44%) with total arterial occlusion occurring in 14 patients (16%). Medial fibroplasia of the renal artery progressed in 22 patients (33%) with no patient progressing to complete occlusion. Reduction in kidney size and increase in serum creatinine were good clinical markers for progressive atherosclerotic renal artery disease, but failed to discriminate between progressive and nonprogressive medial fibroplasia. The adequacy of BP control did not correlate with progressive occlusive disease in patients with either renal artery atherosclerosis or medial fibroplasia. The clinical implications of these observations are discussed with a view toward renal revascularization or transluminal angioplasty for preservation of renal function.


The effects of long-term treatment with the 5-HT1A receptor agonist 8-OH-DPAT and the 5-HT2/1C receptor agonist DOI in the neonatal rat.
The rat pup ultrasonic call was used to study the effects of acute and long-term treatment with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the 5-HT2/1C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) during the neonatal period. Acute administration of 8-OH-DPAT and DOI reduced the number of ultrasonic calls. The reduction induced by 8-OH-DPAT and DOI was antagonized by the 5-HT1A antagonist (S)-5-fluoro-8-hydroxy-2-(di-n-propylamino)tetralin ((S)-UH-301) and the 5-HT2 antagonist ketanserin, respectively. The long-term treatments were started on postnatal day 1. On postnatal day 7, the response of the long-term DOI-treated group was clearly attenuated in comparison to that of the acute DOI-treated group. In contrast, no tolerance to the effect of 8-OH-DPAT was achieved after an analogous treatment. The data indicate that there is a diversity in the ontogeny of the ability to develop tolerance to 5-HT1A agonists in comparison to 5-HT2/1C agonists.


A gradient-free method for the purification of infective dengue virus for protein-level investigations.
Dengue virus (DENV) is a mosquito-transmitted flavivirus that infects approximately 100 million people annually. Multi-day protocols for purification of DENV reduce the infective titer due to viral sensitivity to both temperature and pH. Herein we describe a 5-h protocol for the purification of all DENV serotypes, utilizing traditional gradient-free ultracentrifugation followed by selective virion precipitation. This protocol allows for the separation of DENV from contaminating proteins - including intact C6/36 densovirus, for the production of infective virus at high concentration for protein-level analysis.


A chromosome painting test of the basal eutherian karyotype.
We studied the chromosomes of an Afrotherian species, the short-eared elephant shrew Macroscelides proboscideus with traditional banding techniques and mapped the homology to human chromosomes by in-situ hybridization of human chromosome paints. Here we present for the first time the karyotype of this species, including banding patterns. The chromosome painting allowed us to test various hypotheses of the ancestral Eutherian karyotype, the validity of the radical taxonomic assemblage known as Afrotheria and the phylogenetic position of the elephant shrew within the Afrotheria. Current hypotheses concerning the Eutherian ancestral karyotype include diploid numbers ranging from 2n = 44 to 50 while molecular studies have proposed a new superordinal grouping of extant Eutherians. In particular, the Afrotheria is hotly debated, as it appears to be an odd mixture of species from Ungulata, Tubulidentata, Macroscelidea and Lipotyphla, which have no apparent morphological traits to unite them. The hybridization pattern delimited a total of 37 segments in the elephant shrew genome and revealed 21 different associations of human chromosome segments. Associations 1/19 and 5/21 link all Afrotheria so far studied and support the Afrotheria assemblage. Associations 2/8, 3/20, and 10/17 strongly link aardvarks and elephant shrews after the divergence of the line leading to elephants. The most likely ancestral Eutherian karyotype would be 2n = 48 chromosomes. However, the lack of comparative chromosome painting data between Eutherians and an appropriate outgroup is a severe limitation on attempts to delineate the ancestral genome of Eutherians. Current attempts lack legitimacy until this situation is corrected.


An actin-myosin complex on actively transcribing genes.
Actin and myosin have been individually implicated in different aspects of gene expression. Here, we show in vivo evidence for a specific nucleolar actin-myosin complex physically associated with both the RNA polymerase I holoenzyme and ribosomal genes. We find that this specific actin-myosin complex is functionally coupled to elongating ribosomal RNA transcripts in living cells. From these observations, we conclude that an actin-based myosin motor is associated with transcribing ribosomal genes in the cell nucleus. These results correlate with an involvement of both actin and myosin in regulating mRNA synthesis and suggest that actin-myosin motors may provide a general mechanism to facilitate elongation of RNA transcripts during transcription of both ribosomal genes and protein-coding genes.


The burden of sulfur dioxide pollution on years of life lost from chronic obstructive pulmonary disease: A nationwide analysis in China.
Sulfur dioxide (SO2) is one of the major gaseous pollutants in China and other developing countries. Few multicity studies have been done to examine the short-term effect of SO2 on cause-specific years of life lost (YLL). This study was designed to investigate the burden of chronic obstructive pulmonary disease (COPD) associated with SO2 exposure. A 5-year time-series study was conducted in 48 Chinese cities from 2013 to 2017. Generalized additive models were first used to estimate the city-specific relationship. Then, random-effects meta-analyses were applied to pool the estimates. Furthermore, the roles of potential modifiers and the related economic loss estimated by the method of value per statistical life year were also evaluated. The annual mean concentration of SO2 was 27.1 μg/m3. A 10 μg/m3 increase in 4-day moving average (lag03) of SO2 concentration was associated with 0.83% (95% CI: 0.13%, 1.53%) relative increment in YLL from COPD, and relevant percent change of mortality was 0.78% (95% CI: 0.16%, 1.41%). Moreover, a significantly higher effect was observed in the warm season, particularly in the south region. SO2 exposure was estimated to account for 1.89% of the total economic loss due to YLL from COPD. Our findings showed a positive association between short-term exposure to SO2 and YLL from COPD and highlighted the importance of continuous control of SO2 pollution to reduce corresponding attributable disease burden.


Ex vivo absorption of promestriene from oil-in-water emulsion into infant foreskin.
Hypospadias is a birth defect in which the urinary tract opening is not at the tip of the penis. Hypospadias surgery is frequently complicated by healing deficiencies. Topical treatments with oestrogens were reported to improve healing. In the present study, ex vivo percutaneous absorption of promestriene, a synthetic oestrogen resulting of the double esterification of estradiol was conducted as a pre-requisite for further clinical trial in infants. Penetration of promestriene into infant foreskin treated with commercial oil in water emulsion (10 μg mg(-1)) for 24 h was characterized showing controlled release properties enabling epidermal concentration more than six times higher than dermal concentration (4.13±2.46 mg g(-1) versus 0.62±0.84 mg g(-1), respectively). Furthermore, apparent promestriene fluxes into and through the skin (i.e., 1.5 μg cm(-2) h(-1) and<0.89 μg cm(-2) h(-1), respectively) were calculated from (i) drug amount retained into epidermis and dermis, or (ii) the limit of detection into the receptor fluid. In conclusion, less than 2% of initial dose were absorbed within 24h which compared well with others steroids applied topically in colloidal systems.


Propylene Glycol-Free Melphalan versus PG-Melphalan as Conditioning for Autologous Hematopoietic Cell Transplantation for Myeloma.
High-dose melphalan (Mel) conditioning before autologous hematopoietic cell transplantation (autoHCT) is standard of care for patients with transplantation-eligible multiple myeloma. The traditional lyophilized Mel formulation has inadequate solubility and stability after reconstitution, leading to the use of propylene glycol (PG) as a solubilizing agent. A newer PG-free Mel preparation (Evomela) uses beta cyclodextrin captisol as a solubilizing agent and was approved by the United States Food and Drug Administration as a conditioning agent based on a single-phase IIb study showing bioequivalence. We compared the outcomes of consecutive patients with myeloma undergoing autoHCT using the 2 formulations of Mel for conditioning as our center switched from using the older formulation (PG-Mel) to the newer one (PGF-Mel). Of 294 autoHCT recipients, 162 received PG-Mel conditioning and 132 received PGF-Mel conditioning. The PGF-Mel group was older and had a lower average Karnofsky Performance Status score. PGF-Mel was associated with faster neutrophil recovery (median, 12 days versus 13 days; P < .001), fewer grade 3-4 infections within 30 days of autoHCT (1.5% versus 8.0%; P = .048), and a lower 30-day rehospitalization rate (6.8% versus 17.9%; P = .04), as confirmed by propensity-weighted analysis. No significant between-group differences were detected in mucositis, organ toxicity, myeloma response, or 100-day mortality.


Effect of salinity on the biosynthesis of n-3 long-chain polyunsaturated fatty acids in silverside Chirostoma estor.
The genus Chirostoma (silversides) belongs to the family Atherinopsidae, which contains around 150 species, most of which are marine. However, Mexican silverside (Chirostoma estor) is one of the few representatives of freshwater atherinopsids and is only found in some lakes of the Mexican Central Plateau. However, studies have shown that C. estor has improved survival, growth, and development when cultured in water conditions with increased salinity. In addition, C. estor displays an unusual fatty acid composition for a freshwater fish with high docosahexaenoic acid (DHA)/ eicosapentaenoic acid (EPA) ratios. Freshwater and marine fish species display very different essential fatty acid metabolism and requirements, and so the present study investigated long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis to determine the capacity of C. estor for endogenous production of EPA and DHA, and the effect that salinity has on these pathways. Briefly, C. estor were maintained at three salinities (0, 5, and 15 ppt), and the metabolism of ¹⁴C-labeled 18:3n-3 was determined in isolated hepatocyte and enterocyte cells. The results showed that C. estor has the capacity for endogenous biosynthesis of LC-PUFA from 18-carbon fatty acid precursors, but that the pathway was essentially only active in saline conditions with virtually no activity in cells isolated from fish grown in freshwater. The activity of the LC-PUFA biosynthesis pathway was also higher in cells isolated from fish at 15 ppt compared with fish at 5 ppt. The activity was around fivefold higher in hepatocytes compared with enterocytes; although the majority of 18:3n-3 was converted to 18:4n-3 and 20:4n-3 in hepatocytes, the proportions of 18:3n-3 converted to EPA and DHA were higher in enterocytes. The data were consistent with the hypothesis that conversion of EPA to DHA could contribute, at least in part, to the generally high DHA/EPA ratios observed in the tissue lipids of C. estor.


Metabolomic analysis of follicular fluid from women with Hashimoto thyroiditis.
Hashimoto thyroiditis is an autoimmune disease characterized by hypothyroidism and a high level of anti-thyroid autoantibodies. It has shown to negatively impact female fertility; however, the mechanisms are unclear. Ovarian follicular fluid appears to be the key to understanding how Hashimoto thyroiditis affecst fertility. Thus, we aimed to evaluated the metabolic profile of follicular fluid and antithyroid autoantibody levels in the context of Hashimoto thyroiditis. We collected follicular fluid from 61 patients, namely 38 women with thyroid autoantibody positivity and 23 women as negative controls, undergoing in vitro fertilization treatment. Follicular fluid samples were analyzed using metabolomics, and thyroid autoantibodies were measured. Fifteen metabolites with higher concentrations in the follicular fluid samples from Hashimoto thyroiditis were identified, comprising five possible affected pathways: the glycerophospholipid, arachidonic acid, linoleic acid, alpha-linolenic acid, and sphingolipid metabolism pathways. These pathways are known to regulate ovarian functions. In addition, antithyroglobulin antibody concentrations in both serum and follicular fluid were more than tenfold higher in women with Hashimoto thyroiditis than in controls. Our data showed that the metabolic profile of follicular fluid is altered in women with Hashimoto thyroiditis, suggesting a potential mechanistic explanation for the association of this disease with female infertility.


Using coronary computerized tomographic images to predict the bulging second genu of the facial nerve in mastoidectomy.
The aim of the present study is to determine whether coronary CT images of the temporal bone are useful to predict a bulging second genu of the facial nerve (SGFN) in mastoidectomy by measuring and comparing the heights of the SGFN above the prominence of the lateral semicircular canal (PLSC) in medial-to-lateral dimension on coronary CT images and in mastoidectomy. The relationship between the SGFN and the PLSC in medial-to-lateral dimension, which may have big variability, can be evaluated on the coronary CT images of the temporal bone. The heights of the SGFN above the PLSC in medial-to-lateral dimension were measured on coronary CT images and in mastoidectomy in 184 patients. If the SGFN is above the PLSC in medial-to-lateral dimension, we called the SGFN a bulging SGFN. The data measured on CT images and in surgery were described in histograms and compared. The sensitivity and the specificity in the diagnosis of a bulging SGFN on CT images were calculated by comparison with surgical measurement. Cohen's kappa coefficient was calculated. The heights of the SGFN above the PLSC measured in medial-to-lateral dimension varied from -2.9 to 2.9 mm on coronary CT images and varied from -3.0 to 3.0 mm in surgery. The data measured in surgery showed that the SGFN was above the PLSC in medial-to-lateral dimension in 27.7% (51/184) patients, at least 1 mm above the PLSC in 15.8% (29/184) patients and at least 2 mm above the PLSC in 6.0% (13/184) patients. The sensitivity and the specificity for CT diagnosis of a bulging SGFN were 100% (51/51) and 91.0% (121/133), respectively. Bulging SGFN can be predicted by measuring the height of the SGFN above the PLSC on coronary CT images of the temporal bone.


Comparison of the shear bond strength of RMGIC to a resin composite using different adhesive systems: An in vitro study.
This study evaluated and compared the role of newer dental adhesives to bond composite resin to the resin modified glass ionomer (RMGIC) liner. Thirty-six specimens were prepared on acrylic blocks, with wells prepared in it by drilling holes, to retain the RMGIC. The specimens were randomly divided into three groups of 12 specimens each. In group I, a thin layer of an adhesive, which was a Total-etch type (Adper Single bond-2), was applied between RMGIC and the composite resin. Ingroup II, a Self-Etch adhesive (Adper prompt-L pop) was applied, and in group III there was no application of any adhesive between RMGIC and the composite resin. After curing all the specimens, the shear bond strength was measured using an Instron universal testing machine. The results were drawn and tabulated using ANOVA-fishers and Tukey's statistical tests. The maximum shear bond strength values were recorded in group II specimens with the self-etch adhesive (Adper prompt-L pop), showing a mean value of 5.826 when compared to the group I adhesive-Total-etch type with a mean shear bond strength of 4.6380, while group III specimens, where no adhesive was used, showed a minimum mean shear bond strength of 2.8385. There was a great and significant difference between group I and group II (P value 0.003), whereas, both group I and group II showed a vast and significant difference from group III (P value 0 - 001). Hence, this present study concludes that application of Self-Etch adhesive (Adper prompt-L pop) in between RMGIC and composite resin increases the shear bond strength between RMGIC and the resin composites, as compared to the Total-etch type adhesives (Adper Single Bond 2), as well as, without application of the adhesive agent.


An enhance multimodal multiobjective optimization genetic algorithm with special crowding distance for pulmonary hypertension feature selection.
Multiobjective optimization assumes a one-to-one mapping between decisions and objective space, however, this is not always the case. When many variables have the same or equivalent objective value, a multimodal multiobjective issue develops in which more than one Pareto Set (PS) maps to the same Pareto Front (PF). Evolutionary computing research into multimodal multiobjective optimization issues has increased (MMOPs). This paper proposed an enhanced multimodal multiobjective genetic algorithm to crack MMOPs using a special crowding distance calculation (ESNSGA-II). This special crowding distance calculation can consider the diversity of the decision space while paying attention to the diversity of the object space. Then, a unique crossover mechanism is established by combining the simulated binary crossover (SBX) method with the capacity of Pareto solutions to generate offspring solutions. The balance between convergence and diversity in both decision space and object space can be guaranteed synchronously, and PS distribution and PF accuracy may both be enhanced. The proposed ESNSGA-II uses the CEC2020 benchmarks MMF1-MMF8 to assess its properties. Comparing the ESNSGA-II to other recently established multimodal multiobjective evolutionary techniques demonstrates that it is capable of efficiently searching numerous PSs of MMOPs. Finally, the suggested ESNSGA-II is used to address a real MMOP problem of pulmonary hypertension detection via arterial blood gas analysis. The statistical analysis reveals that the suggested ESNSGA-II algorithm outperforms other algorithms on this MMOP, and so may be considered a possible tool for pulmonary hypertension.