Microdialysis of excitatory amino acids in the periaqueductal gray of the rat after unilateral peripheral inflammation.
This study measured the release of glutamate (Glu) and aspartate (Asp) amino acid transmitters in the ventrocaudal compartment of the rat periaqueductal gray (PAG) following exposure to unilateral peripheral inflammation. The release of endogenous Glu and Asp from the rat ventrocaudal PAG was monitored with the microdialysis technique in unanesthetized, unrestrained rats. There was significant increase (1,300%) in the basal concentrations of Glu release in the 7 days Complete Freund's Adjuvant (CFA) treated group compared to 24 h mineral oil control group. Amino acid release was induced by infusing veratridine (75 microM, a sodium channel activator) directly through the 1 mm long dialysis probe. Perfusion of veratridine into the ventrocaudal PAG resulted in significant elevation of Glu and Asp amino acids. In the 24 h and 7 days CFA treated rats, veratridine-evoked release of Glu was significantly decreased in the lateral ventrocaudal PAG compared to control rats injected with mineral oil (CFA vehicle). The peak minus baseline concentrations of Glu in 24 h and 7 days CFA treated groups decreased 55.7% and 43.9%, respectively. In contrast, The basal and the peak minus baseline concentrations of Asp showed no significant change between control group and 24 h and 7 days CFA treated animals. The results provide direct evidence that Glu excitatory amino acid may be involved in nociception/nociception modulation pathway in the ventrocaudal PAG.


Right ventricle early inflow-outflow index may inform about the severity of pneumonia in patients with COVID-19.
Echocardiography is generally used in our daily practice to detect cardiovascular complications in COVID-19 patients and for etiological research in the case of worsened clinical status. Many echocardiographic parameters have been the subject of investigation in previous studies on COVID-19. Recently, the right ventricle early inflow-outflow (RVEIO) index has been identified as a possible and indirect marker of the severity of tricuspid regurgitation and right ventricular dysfunction in pulmonary embolism. In this study, we aimed to investigate the relationship between the severity of pneumonia in COVID-19 patients and the RVEIO index. A total of 54 patients diagnosed with COVID-19 pneumonia were enrolled in this study. Our study population was separated into two groups as severe pneumonia and nonsevere pneumonia based on computed tomography imaging. Saturation O2 , C-reactive protein, D-dimer, deceleration time, tricuspid annular plane systolic excursion, tricuspid lateral annular systolic velocity, and RVEIO index values were found to be significantly different between severe and nonsevere pneumonia groups. The result of the multivariate logistic regression test revealed that saturation O2, D-dimer, Sm, and RVEIO index were the independent predictive parameters for severe pneumonia. Receiver operating characteristic curve analysis demonstrated that RVEIO index >4.2 predicted severe pneumonia with 77% sensitivity and 79% specificity. The RVEIO index can be used as a bedside, noninvasive, easily accessible, and useful marker to identify the COVID-19 patient group with widespread pneumonia and, therefore high risk of complications, morbidity, and mortality.


[Advances on Recognizing and Managing Tumor Heterogeneity].
Tumor heterogeneity is one of the characteristics of malignant tumors, which can cause differences in tumor growth rate, invasion, migration, drug sensitivity and prognosis. Discoveries and development upon on tumor-driver genes and targeted therapy paved the way on dealing with cancer diagnosis and treatment. However, the existence of tumor heterogeneity makes malignant tumor more hardly to overcome. It is generally present and far more complicated during the process of cancer recurrence, development and evolution. Thus, it has becoming key areas in precision medicine regarding to designing optimal therapeutic approaches targeting the mechanisms and phenotypes of tumor heterogeneity, based on novel detecting techniques and new concepts and theory. This review summarized the current references on tumor heterogeneity, in order to better understand the function and mechanisms, and eventually manage tumor heterogeneity through various methods. .


Molecular and chemical monitoring of growth and ochratoxin a biosynthesis ofP. verrucosum in wheat stored at different moisture conditions.
The growth and ochratoxin A producing activity at the phenotypical and molecular level ofP. verrucosum in wheat stored at different relative moisture conditions have been followed. Growth has been measured by determination of colony forming units (cfu). The expression of the ochratoxin A polyketide synthase (otapksPV) has been followed over time by reverse transcriptase Real Time PCR, whereas the biosynthesis of ochratoxin A by the fungus has been followed by HPLC. The remoisted and inoculated wheat was kept in perforated plastic bags and stored in tower silos. The bags were adjusted to 24%, 19% and 14% (m/m) relative moisture and stored for 6 month (September 06 - February 06) at ambient temperatures. A high increase of the cfu number up to a level of about lx10(8) cfu/g could be observed in the 24% sample. Interestingly no growth could be detected in the 14% and 19% samples. This result was supported by the quantitative Real Time PCR data. In congruence with this growth behaviour ochratoxin A could be detected from the first to the last time point in the 24% sample. Interestingly the ochratoxin A amounts measured over time did not show increasing or constant values, but varied from higher to lower values. After storage of three month (November 2006) the ochratoxin A concentration in the wheat was highest. The expression of theotapksPV gene mirrors this behaviour. The expression of this gene also fluctuates around a certain value, showing high activity after three month of storage.


Acetone butanol ethanol (ABE) production from concentrated substrate: reduction in substrate inhibition by fed-batch technique and product inhibition by gas stripping.
Acetone butanol ethanol (ABE) was produced in an integrated fed-batch fermentation-gas stripping product-recovery system using Clostridium beijerinckii BA101, with H(2) and CO(2) as the carrier gases. This technique was applied in order to eliminate the substrate and product inhibition that normally restricts ABE production and sugar utilization to less than 20 g l(-1) and 60 g l(-1), respectively. In the integrated fed-batch fermentation and product recovery system, solvent productivities were improved to 400% of the control batch fermentation productivities. In a control batch reactor, the culture used 45.4 g glucose l(-1) and produced 17.6 g total solvents l(-1) (yield 0.39 g g(-1), productivity 0.29 g l(-1) h(-1)). Using the integrated fermentation-gas stripping product-recovery system with CO(2) and H(2) as carrier gases, we carried out fed-batch fermentation experiments and measured various characteristics of the fermentation, including ABE production, selectivity, yield and productivity. The fed-batch reactor was operated for 201 h. At the end of the fermentation, an unusually high concentration of total acids (8.5 g l(-1)) was observed. A total of 500 g glucose was used to produce 232.8 g solvents (77.7 g acetone, 151.7 g butanol, 3.4 g ethanol) in 1 l culture broth. The average solvent yield and productivity were 0.47 g g(-1) and 1.16 g l(-1) h(-1), respectively.


Higher prevalence of metabolic disorders in patients with bilateral primary aldosteronism than unilateral primary aldosteronism.
Metabolic syndrome (MetS) is a frequent clinical condition in hypertension patients and is more frequently reported in primary aldosteronism (PA). This study is aimed at investigating the prevalence of MetS and its components in the two major types of patients with adrenal venous sampling (AVS)-confirmed unilateral PA and bilateral PA. This was a retrospective cross-section study. We analysed metabolic parameters from 169 PA patients subtyped by AVS, including 85 unilateral PA patients and 84 bilateral PA patients, and we also included 169 non-PA patients matched for age and sex. Patients with unilateral PA had higher concentrations of aldosterone and lower serum potassium than patients with bilateral PA. However, patients with bilateral PA had higher prevalence of MetS (79.8% vs 64.7%, P = .029), obesity (40.5% vs 24.7%, P = .029), dyslipidemia (72.6% vs 55.3%, P = .019) and hyperglycaemia (29.8% vs 16.5%, P = .040) than those with unilateral PA. Meanwhile, bilateral PA had higher BMI (27.55 ± 4.58 vs 25.57 ± 3.28 kg/m2 , P = .001), waist circumference (98.54 ± 11.44 vs 93.32 ± 10.64 cm, P = .003) and fasting plasma glucose (4.98 ± 1.16 vs 4.64 ± 0.93 mmol/L, P = .034). The logistic regression analysis also showed that bilateral PA was associated with the presence of MetS after adjustment for age, sex and duration of hypertension. Patients with bilateral PA have a higher prevalence of MetS than those with unilateral PA, despite unilateral PA patients exhibiting higher concentrations of aldosterone and lower serum potassium, suggesting that unilateral PA and bilateral PA may have differing mechanisms of MetS.


[Transthoracic puncture and excavated pulmonary lesion. Diagnostic contribution and value of the extemporaneous cytologic test].
Twenty-six cases of excavated pulmonary masses are reported. In 18 cases malignancy was proven by transparietal needle aspiration. A false-negative result was due to the needle being introduced too centrally and bringing pus, whereas the tumour was an epidermoid carcinoma. The seven non-malignant lesions consisted of abscess in 4 cases, tuberculosis in 1 case and pulmonary embolism in 2 cases. The sensitivity and specificity of the technique were similar to those observed in large series of transparietal needle aspiration of solid masses. Using thin needles and extemporaneous cytology reduced the number of complications: haemothorax 6 percent, haemoptysis 0.4 percent. The authors conclude that in excavated pulmonary masses transparietal needle aspiration provides a diagnosis of malignancy when the radiological and clinical courses and bronchial fibroscopy are inconclusive. Transparietal needle aspiration avoids the need for other investigations, such as exploratory thoracotomy, thereby reducing the cost of diagnosis.


Automatic analysis algorithm for acquiring standard dental and mandibular shape data using cone-beam computed tomography.
This study aims to introduce a new algorithm developed using retrospective cone-beam computed tomography (CBCT) data to obtain a standard dental and mandibular arch shape automatically for an optimal panoramic focal trough. A custom-made program was developed to analyze each arch shape of randomly collected 30 CBCT images. First, volumetric data of the mandible were binarized and projected in the axial direction to obtain 2-dimensional arch images. Second, 30 patients' mandibular arches were superimposed on the center of the bilateral distal contact points of the mandibular canines to generate an average arch shape. Third, the center and boundary of a panoramic focal trough were obtained using smoothing splines. As a result, the minimum thickness and transition of the focal trough could be obtained. If this new algorithm is applied to big data of retrospective CBCT images, standard focal troughs could be established by race, sex, and age group, which would improve the image quality of dental panoramic radiography.


Prevalence of intestinal parasitic infections and associated risk factors for hookworm infections among primary schoolchildren in rural areas of Nakhon Si Thammarat, southern Thailand.
Soil-transmitted helminth (STH) infections are among the most common type of infections worldwide and are widely distributed in tropical areas. In rural areas of southern Thailand where most land is used for agriculture, children are at risk of acquiring parasites, especially STHs. Assessing the current situation regarding parasitic infection in these areas is a prerequisite for developing appropriate control measures. This study is aimed at determining the prevalence of intestinal parasitic infections, the intensity of STH infections and the associated risk factors among primary schoolchildren in Nopphitam District, Nakhon Si Thammarat Province, Thailand. A cross-sectional study involving 299 schoolchildren between 7 and 12 years of age was conducted between January and March 2016. A questionnaire administered by direct interviews was used to collect sociodemographic information and data on associated risk factors. Stool samples were processed using direct wet smears, formalin-ethyl acetate sedimentation concentration, and the modified Kato-Katz technique. The overall prevalence of intestinal parasites among the 299 children was 16% (48 of 299), with 32 children infected with hookworms (10.7%), 10 with Blastocystis hominis (3.3%), seven with Giardia intestinalis (1.6%), one with Enterobius vermicularis (0.3%), and one with Trichuris trichiura (0.3%). The hookworm infection intensity, measured by the median eggs per gram (EPG) of stool, was 1200 EPG (Interquartile range (IQR): 360-3200). Most children had light-intensity hookworm infections, but two had heavy-intensity infections. When participants included in the sample were classified by age, children 10-12 years old demonstrated higher intestinal parasite prevalence than those aged 7-9 years (adjusted odds ratio (AOR) = 2.3, 95% CI: 1.1-4.9, P = 0.030). Inadequate handwashing before meals was statistically associated with hookworm infections (AOR = 2.3; 95% CI: 1.1-4.8, P = 0.037). This study highlights that hookworms are the most prevalent STH infection in the study area. Older age group (10-12 years) and inadequate handwashing before meals were statistically associated with hookworm infections. Accordingly, appropriate strategies and education on personal and environmental hygiene should be implemented. Moreover, the cost-effectiveness of mass drug administration in this area should be further investigated.


Generating ideas for research: an Australian research experience.
Recent changes in the educational system and career developments in Australia have provided Australian clinical nurses with an opportunity to conduct research in their practice. In this article, the nursing staff of an Australian gastroenterology unit describe their experience in defining a research project.


PC-based visual stimuli for behavioural and electrophysiological studies of optic flow field detection.
A PC-based visual-stimulus-generation package for behavioural and electrophysiological studies of responses to optic flow is described. Developed for studies of crab vision, the package is particularly well suited for use with animals that have very large fields of view, i.e. +/-120 degrees. Programs, written in the Borland Delphi language, use the OpenGL graphics library to create realistic representations of motion in a three dimensional environment. Large-field stimuli include simulations of self-motion (rotation and translation, separately or in combination) relative to a square-wave grating or other, user-selected, background. The package also includes representations of approaching and receding objects, and rotating spiral patterns for the investigation of neural responses to looming/anti-looming. Additionally, the package provides local motion stimuli, translating or rotating targets presented at many points in the receptive field, which can be used to derive response maps of large-field motion-sensitive interneurones. In all these stimuli, inconsistencies in animation timing that have hitherto hindered the use of standard PCs running Microsoft Windows for such applications have been minimised by using an improved real-time clock to control the animation cycle.


Evaluation of bone height and bone density after tooth extraction: an experimental study in minipigs.
The objective of this study was to radiographically quantify bone density and bone height preservation in tooth extraction alveolus filled with xenograft. The maxillary and mandibular fourth deciduous molars and fourth premolars of 6 minipigs were removed. Randomly, in 3 animals the right side was used as the test side and in the other 3 animals the left side was the test side. Intraoral radiographs were performed to compare the condition at the initial time and 3 months later. Measurements of bone height and bone density were performed using KS300 (Zeiss) software. After 3 months, there was a statistically significant smaller bone height loss for the test group. The test group presented a statistically greater bone density immediately after tooth extraction. However, after 3 months there was no statistically significant difference between the groups. The results suggest that treatment of postextraction alveolus with xenograft can preserve bone height initially but differences in bone density compared to when no xenograft is used are not sustained.


Neuro-heuristic analysis of surveillance video in a centralized IoT system.
Security systems are based on the monitoring of specific areas of the facility. The cameras record the selected place for the whole day. Unfortunately, it is difficult to automatically analyze the recorded situations mainly through manual analysis. In this paper, we propose an innovative automatic monitoring data analysis system. To minimize the amount of processed data, a heuristic-based method is proposed to analyze frames. Heuristic algorithm is adapted to image analysis. If the algorithm detects significant changes in pixel values, the frame is sent further to the convolutional neural network. The proposed solution is based on centralized federated learning that allows training a shared model on a local dataset. This guarantees surveillance recordings' privacy with a shared model. The proposal is a hybrid solution that was presented as a mathematical model, tested and compared with other known solutions. Based on conducted experiments, the proposed image processing system minimizes the number of calculations by the hybrid approach that can be valuable for IoT applications. The proposed solution is more effective than the existing solution due to the use of classifiers for the analysis of single frames.


A comparison of Australian rural and metropolitan cardiovascular risk and mortality: the Greater Green Triangle and North West Adelaide population surveys.
Cardiovascular (CVD) mortality disparities between rural/regional and urban-dwelling residents of Australia are persistent. Unavailability of biomedical CVD risk factor data has, until now, limited efforts to understand the causes of the disparity. This study aimed to further investigate such disparities. Comparison of (1) CVD risk measures between a regional (Greater Green Triangle Risk Factor Study (GGT RFS, cross-sectional study, 2004-2006) and an urban population (North West Adelaide Health Study (NWAHS, longitudinal cohort study, 2004-2006); (2) Australian Bureau of Statistics (ABS) CVD mortality rates between these and other Australian regions; and (3) ABS CVD mortality rates by an area-level indicator of socioeconomic status, the Index of Relative Socioeconomic Disadvantage (IRSD). Greater Green Triangle (GGT, Limestone Coast, Wimmera and Corangamite Shires) of South-Western Victoria and North-West Adelaide (NWA). 1563 GGT RFS and 3036 NWAHS stage 2 participants (aged 25-74) provided some information (self-administered questionnaire +/- anthropometric and biomedical measurements). Age-group specific measures of absolute CVD risk, ABS CVD mortality rates by study group and Australian Standard Geographical Classification (ASGC) region. Few significant differences in CVD risk between the study regions, with mean absolute CVD risk ranging from approximately 1% in the age group 35-39 years to 14% in the age group 70-74 years. [corrected]. Similar mean 2003-2007 (crude) mortality rates in GGT (98, 95% CI 87 to 111), NWA (103, 95% CI 96 to 110) and regional Australia (92, 95% CI 91 to 94). NWA mortality rates exceeded that of other city areas (70, 95% CI 69 to 71). Lower measures of socioeconomic status were associated with worse CVD outcomes regardless of geographic location. Metropolitan areas do not always have better CVD risk factor profiles and outcomes than rural/regional areas. Needs assessments are required for different settings to elucidate relative contributions of the multiple determinants of risk and appropriate cardiac healthcare strategies to improve outcomes.


Effect of albumin on the solubility of cholesterol in bile.
Despite the fact that a considerable amount of albumin is present in bile, little is known about the effect of albumin on micellar solubility of cholesterol. The effect of albumin on solubility of cholesterol in various micellar bile salt solutions was studied using Millipore filtration after equilibration. In addition, partitioning of cholesterol from micellar solution was studied using a polyethylene disc method. Decrease of the solubility of cholesterol by the presence of albumin was observed only in unconjugated bile salt solution. The lowering effect of albumin on the cholesterol solubility was found to be proportional to the hydrophobicity of bile salt. In contrast, albumin had almost no effect on cholesterol solubility, either in conjugated bile salt solution or in micellar bile salt solution containing phosphatidylcholine. Addition of albumin enhanced the partitioning of cholesterol out of the micelles in sodium chenodeoxycholate solution as a result of decreased micellar solubility and increased the aqueous solubility of cholesterol in the presence of albumin. Therefore, conjugated bile salt and phosphatidylcholine exert a buffering action on the albumin-induced adverse effect on cholesterol solubility, thus stabilising bile against inadvertent precipitation of cholesterol.


Bilirubin-Displacing Effect of Ceftriaxone in Infants With Unconjugated Hyperbilirubinemia Born at Term.
To evaluate the effect of intravenous (IV) ceftriaxone on free bilirubin concentrations in infants with unconjugated hyperbilirubinemia born at term. A prospective study was performed with subjects serving as their own controls. Our inclusion criteria were infants born at term <7 days old with sepsis and receiving IV antibiotics for >3 days and resolving hyperbilirubinemia with total serum bilirubin levels between 6 and12 mg/dL by day 4 of life. Free bilirubin concentrations were measured by the peroxidase method using a UB analyzer and a Zone Fluidics device before (baseline) and 15 minutes after (follow-up) IV ceftriaxone administration on postnatal days 4 to 6. Paired measurements of free bilirubin were analyzed using a Student paired t-test or Wilcoxon signed-rank test. In total, 27 infants were studied. The mean free bilirubin (μg/dL) at follow-up was not different from that at baseline when measured by the UB analyzer (P = .78). The mean free bilirubin was significantly lower at follow-up compared with baseline when measured by the Zone Fluidics device (P = .02). The ratio of a free bilirubin with and without ceftriaxone, an index of displacing effect, was 1.02 (95% CI 0.89-1.14) using the UB analyzer and 0.58 (95% CI 0.30-0.86) using the Zone Fluidics device. Ceftriaxone is not associated with a bilirubin-displacing effect in infants with a mild unconjugated hyperbilirubinemia. Home therapy with once-daily intramuscular ceftriaxone may be an alternative option for management of sepsis in asymptomatic infants with a mild unconjugated hyperbilirubinemia born at term.


Anaphylaxis to clindamycin following cutaneous exposure.
The role and importance of skin barrier as an immunologic organ and as a potent way of sensitization is well known. However, antibiotics anaphylaxis following skin sensitization has not been reported. We describe the first case of intravenous clindamycin anaphylaxis, with likely sensitization due to previous topical exposure to clindamycin gel for acne in a 14-year-old boy with history of atopy and mild atopic dermatitis. This case highlights the potential sensitization to drug allergens, including antibiotics, via the skin.


Lipolytic and circulatory responses to noradrenaline infusion in hypothyroid subjects before and during thyroxine substitution.
The hypothyroid state in humans is associated with a diminished lipolytic response to noradrenaline in adipose tissue in vitro. In the present study we have investigated the situation in vivo in order to see if such a change in receptor response could be demonstrated in adipose tissue and in the circulatory system. The change in glycerol production rate, induced by an infusion of noradrenaline, was used as an index of adipose tissue adrenergic responsiveness. The results showed that the lipolytic response was decreased by about 50% in the hypothyroid state and that it was normalized when the substitution dose had been increased to 0.10-0.15 mg/day thyroxine. The circulatory response was monitored by measurements of blood pressure and pulse rate. The resting diastolic pressure was transiently lowered by substitution. Similarly the rise in systolic blood pressure induced by l-noradrenaline was transiently increased by substitution. Thus no clear-cut change in receptor response with substitution could be demonstrated by measuring BP and pulse rate only. This result could be due to the fact that the system is more complex than the adipose tissue. The finding of a reduced adrenergic receptor response in vivo in the adipose tissue is in accordance and extends earlier findings in vitro.


Angiotensin-converting enzyme activity in serum and bronchoalveolar lavage fluid after damage to the alveolo-capillary barrier in the human lung.
Angiotensin-converting enzyme (ACE) is considered as a possible marker for endothelial cell damage in serum or bronchoalveolar lavage fluid. This hypothesis was tested during cardiac surgery and during the adult respiratory distress syndrome. We used patients with an expected different degree of endothelial cell damage. ACE levels in serum and bronchoalveolar lavage fluid were compared with indirect markers of alveolo-capillary barrier integrity. Interdisciplinary team in a university hospital. 13 Cardiac surgery patients received no glucocorticoids and 13 others received 2 g methylprednisolone before extracorporeal circulation. Thirteen patients were used as controls and 15 patients had nonseptic adult respiratory distress syndrome. All underwent bronchoalveolar lavage for ACE determination. At different times during surgery serum angiotensin-converting enzyme levels were not significantly different between the two groups. In post-operative bronchoalveolar lavage fluid, angiotensin-converting enzyme levels were significantly higher in patients who received corticoids (27.8 +/- 1.7 U/l, mean +/- SEM), compared to patients without corticoids (19.8 +/- 1.4 U/l), control patients (18.2 +/- 1.3 U/l) or patients with full blown non-septic adult respiratory distress syndrome (18.8 +/- 1.1 U/l). There were no correlations between lavage angiotensin-converting enzyme and other parameters for alveolo-capillary membrane integrity in the lavage fluid such as the number of neutrophil cells, albumin or protein concentration, and between lavage angiotensin-converting enzyme and PaO2/FIO2 ratio during lavage. Angiotensin-converting enzyme activity in serum or bronchoalveolar lavage fluid does not reflect damage of endothelial cells or damage of alveolocapillary integrity in acute pulmonary disease.


Fatty acid variability in three medicinal herbs of Panax species.
Fatty acid profiling has been widely used in the bacteria species identification, we hypothesized that fatty acid characteristics might discriminate the Panax herbs according to species. To test the hypothesis, fatty acids of Panax species, including Panax ginseng, Panax notoginseng and Panax quinquefolius, were characterized and compared using gas chromatography-mass spectrometry (GC-MS) followed by multivariate statistical analysis. The content of investigated 11 fatty acids, including myristic acid, pentadecanoic acid, palmitic acid, palmitoleic acid, heptadecanoic acid, stearic acid, oleic acid, linoleic acid, α-linolenic acid, arachidic acid and eicosadienoic acid, obviously varied among three species, suggesting each species has its own fatty acid pattern. Principal component analysis and hierarchical clustering analysis according to the absolute and relative contents of fatty acids, showed that 30 tested samples could be clearly differentiated according to the species. These findings demonstrated that GC-MS-based fatty acid profiling coupled with multivariate statistical analysis provides reliable platform to classify these three Panax species, which is helpful for ensuring their safety and efficacy.


Immunohistochemical localization of GDNF in the human hippocampal formation from prenatal life to adulthood.
In this study, we examined the immunohistochemical occurrence and distribution of glial cell line-derived neurotrophic factor (GDNF) in autoptic specimens of normal human hippocampus at different ages, from 22 weeks of gestation (w.g.) to adult life. Two different anti-GDNF polyclonal antibodies were used. Western blot analysis on homogenates of human and rat brain and recombinant human GDNF resulted in differential detection of monomeric and dimeric forms of the proteins. The ABC immunohistochemical technique revealed that in the Ammon's horn, numerous positive cell bodies occurred in the pyramidal layer, the majority of them being present in the proximal CA1 and in CA2. Sparse positive neurons could be observed in the stratum oriens and moleculare. In the fascia dentata many granule cells showed a light punctate staining, whereas more heavily labelled neurons occurred in the polymorphic layer and, occasionally, in the molecular layer. The distribution pattern of GDNF-like immunoreactivity appeared consistently similar throughout life stages from 29 w.g. to adult age. However, intensity of labelling and frequency of neuronal cell bodies was highest in the neonate and decreased in adulthood. The present data provide a comprehensive map of the localization of GDNF-like immunoreactive neurons in the human archicortex at developmental ages and in the mature tissue and represent a first step towards the identification of hippocampal neurons which express the protein and/or are responsive to it. They further suggest that GDNF may play a role in the development of intrahippocampal circuitry and in neuronal function and maintenance throughout life.


Management of gastric ectopic pancreas identified in preoperative evaluation of bariatric surgery - A case report.
The diagnosis of gastric lesions, such as the Ectopic Gastric Pancreas (GEP), has become more frequent after the increase in bariatric surgeries. The most frequently used surgical options are: Sleeve Gastrectomy (SG) and Roux-en-Y Gastric Bypass (RYGB). The scientific papers about GEP in Bariatric Surgery consisted of intraoperative findings, approach the lesion with gastrectomy and the need to change the initial surgical strategy of the Sleeve for others techniques which allow extended gastric resections. This is a report on a 21-year-old female patient with class 3 obesity whose preoperative evaluation showed two lesions suggestive of GEP. Simultaneous surgical video-laparoscopic treatment of lesions associated with SG aided by intraoperative Upper Endoscopy (UE) was performed with no perioperative complications. It is possible to associate the treatment of rare gastric lesions with traditional surgery techniques for obesity.


Analysis of mechanisms regulating the expression of parental alleles at the GPD locus in mule erythrocytes.
Erythrocyte glucose-6-phosphate dehydrogenase (G6PD) was examined by 13% starch gel electrophoresis in 74 mules (42 females and 32 males), 35 donkeys, and ten horses. The quantitative expression of the parental alleles at the Gpd locus varies greatly in female mules from the hemizygous expression of the maternal allele to that of the paternal. The data obtained indicate that the X chromosomes are randomly inactivated in females mules. No selective advantage of a cell population with a maternally (or paternally) derived X active was found in female mule erythrocytes. It is suggested that the phenotypic variability in the expression of the parental Gpd alleles is related to the random proportions established between cells having either a maternal or paternal X active in an initiator (stem) cell group giving rise to erythroid tissue. Initiator cell numbers estimated for erythroid tissue (six or seven) are close to those reported for human females and intergeneric fox hybrids. These numbers may vary depending on the duration of the time of determination and the division rate of initiator cells at determination.


The role of REBOA in patients in traumatic cardiac arrest subsequent to hemorrhagic shock: a scoping review.
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a useful adjunct in treatment of patients in severe hemorrhagic shock. Hypothetically, REBOA could benefit patients in traumatic cardiac arrest (TCA) as balloon occlusion of the aorta increases afterload and may improve myocardial performance leading to return of spontaneous circulation (ROSC). This scoping review was conducted to examine the effect of REBOA on patients in TCA. This scoping review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) Statement. PubMed, EMBASE.com and the Web of Science Core Collection were searched. Articles were included if they reported any data on patients that underwent REBOA and were in TCA. Of the included articles, data regarding SBP, ROSC and survival were extracted and summarized. Of 854 identified studies, 26 articles met criteria for inclusion. These identified a total of 785 patients in TCA that received REBOA (presumably less because of potential overlap in patients). This review shows REBOA elevates mean SBP in patients in TCA. The achievement of ROSC after REBOA deployment ranged from 18.2% to 67.7%. Survival to discharge ranged from 3.5% to 12.1%. Overall, weak evidence is available on the use of REBOA in patients in TCA. This review, limited by selection bias, indicates that REBOA elevates SBP and may benefit ROSC and potentially survival to discharge in patients in TCA. Extensive further research is necessary to further clarify the role of REBOA during TCA.


Carcinomas unresponsive to either cisplatinum or anti-EGFR therapy can be growth inhibited by combination therapy of both agents.
Previously we demonstrated that the antitumor efficacy of monoclonal antibodies against the EGFR (epidermal growth factor receptor) of human tumor xenografts mainly depends on the EGFR content of tumors rather than on the tumors' entity. In this study we wanted to elucidate whether the described cumulative effect of cisplatin and Anti-EGFR therapy also depends on the EGFR expression. Xenotransplanted carcinomas with different EGFR levels were treated with monoclonal antibodies against the EGFR (EMD 72000 and EMD 55900), cisplatinum and a combination of both. Each monoclonal antibody alone led to an EGFR-dependent significant tumor growth reduction. Cisplatinum alone had no growth inhibitory effects on tumors with high content in contrast to those with low EGFR content. The combination of antibodies with cisplatinum resulted in an EGFR-independent tumor growth inhibition which was stronger than observed in the case of monotherapy. The obtained results may address upcoming phase I/II trials to use Anti-EGFR/Cisplatinum therapy regardless of the EGFR content of tumors.


Asynchronous maturation of pathways for impulses from muscle and skin receptors to the sensomotor cortex in rabbits.
A comparative analysis was undertaken of the functional and structural maturation of peripheral pathways for the conduction of afferent impulses to the sensomotor cortex from muscle and skin receptors of the sciatic nerve during postnatal ontogeny in rabbits. The criterion of functional maturity of the fibers was their sensitivity to the blocking action of procaine when applied to muscular and cutaneous nerves. Structural maturation of peripheral nerve fibers was determined by the degree of their myelination. Successive blocking of fibers of muscular and cutaneous nerves by procaine was shown to depress certain components of the cortical evoked potential. As the animal develops, the sensitivity of its nerve fibers to procaine and the configuration of the evoked response are modified. Different peripheral projections, maturing at different times, participate in the organization of individual components of the cortical evoked potentials. This also takes place during maturation of peripheral afferent projections from muscular and cutaneous receptors.


Liver Histology: Diagnostic and Prognostic Features.
When patients with suspected drug-induced liver injury (DILI) undergo liver biopsy, the pathologist can provide a wealth of information on the morphologic changes. The most common histologic patterns of DILI include mimics of acute and chronic hepatitis as well as acute cholestasis, chronic cholestasis, and a mixed pattern that combines hepatitis with cholestasis. The pattern may suggest etiologies of injury or correlate with reported patterns of injury for specific agents. Biopsy may exonerate or indict particular drugs as causal agents of injury and provide specific information on severity of injury and specific types of changes related to various outcomes.


Quality of life in patients with ankylosing spondylitis.
Quality of life encompasses the net effects that a patient perceives an illness to have on his or her life. Quality of life commonly includes symptoms, physical functioning, work ability, social interaction, psychological functioning, treatment side effects, and financial costs. In ankylosing spondylitis, although symptoms of pain, stiffness, and fatigue are common and moderately severe, few patients develop severe functional disability and most remain employed. The limited information available suggests that most patients with ankylosing spondylitis have few problems with social interactions, although depression is not uncommon. Direct medical costs of ankylosing spondylitis are low, compared with those of other rheumatic diseases.


Use of the anterolateral thigh free flap for upper-extremity reconstruction.
The anterolateral thigh free flap (ALTF) first was reported in 1984 and has been used in large series with success for a multitude of clinical purposes. We describe our results with the ALTF in upper-extremity and hand reconstruction. From 1996 to 2003 there were 15 patients who had reconstruction of the hand and upper extremity using the ALTF. The parameters used to assess the outcome of our series included the success rate of the flap as measured by flap survival rate and adequacy of skin coverage, ability to close the donor site primarily or necessity of a skin graft, complications associated with the flap, donor site, and non-flap-related complications such as pulmonary embolism. Of the 15 patients with an ALTF, 3 (20%) had a musculocutaneous perforator and 12 (80%) had a septocutaneous perforator. Two patients had a neurotized ALTF reconstruction. There were 4 complications related to the flap with 1 complete flap failure. The overall flap survival rate was 93%. The donor site was closed primarily in 8 patients (53%) and with a skin graft in 7 patients (47%). One donor site breakdown occurred. Our results show many advantages of the ALTF for upper-extremity reconstruction. Because of its versatility the ALTF is suited ideally for upper-extremity reconstruction and should be considered as part of the reconstructive ladder.


Justification of routine venous thromboembolism prophylaxis in head and neck cancer reconstructive surgery.
Venous thromboembolism (VTE) is a preventable complication in which early ambulation is expected after head and neck surgery. Thus, the role of VTE prophylaxis is questionable and needs further assessment. The purpose of this study was to specify the relative contributing risk factors for patients who underwent head and neck cancer ablation with immediate reconstruction. A retrospective analysis was conducted of consecutive head and neck cancer ablations with immediate reconstructions between 2008 and 2013. Dextran and prostaglandin E2 (PGE2) were routinely given as flap thromboprophylaxis. Logistic regression was applied to analyze the potentially significant risk factors. Of 1953 subjects, the incidence of symptomatic VTE was 2.2% with 0.1% mortality rate. Prolonged surgery (>592.5 minutes; P = .048), immobilization (>4 days; P = .019), and subjects without postoperative flap thromboprophylaxis (P = .002) are significant risk factors for VTE development. Our flap thromboprophylaxis regime might have played a crucial role in keeping the incidence of VTE low. Despite prolonged immobilization in fibula flap reconstruction, the incidence of VTE remained low when flap thromboprophylaxis was given.


Detection of right-to-left shunts: comparison between the International Consensus and Spencer Logarithmic Scale criteria.
International Consensus Criteria (ICC) consider right-to-left shunt (RLS) present when Transcranial Doppler (TCD) detects even one microbubble (microB). Spencer Logarithmic Scale (SLS) offers more grades of RLS with detection of >30 microB corresponding to a large shunt. We compared the yield of ICC and SLS in detection and quantification of a large RLS. We prospectively evaluated paradoxical embolism in consecutive patients with ischemic strokes or transient ischemic attack (TIA) using injections of 9 cc saline agitated with 1 cc of air. Results were classified according to ICC [negative (no microB), grade I (1-20 microB), grade II (>20 microB or "shower" appearance of microB), and grade III ("curtain" appearance of microB)] and SLS criteria [negative (no microB), grade I (1-10 microB), grade II (11-30 microB), grade III (31100 microB), grade IV (101300 microB), grade V (>300 microB)]. The RLS size was defined as large (>4 mm) using diameter measurement of the septal defects on transesophageal echocardiography (TEE). TCD comparison to TEE showed 24 true positive, 48 true negative, 4 false positive, and 2 false negative cases (sensitivity 92.3%, specificity 92.3%, positive predictive value (PPV) 85.7%, negative predictive value (NPV) 96%, and accuracy 92.3%) for any RLS presence. Both ICC and SLS were 100% sensitive for detection of large RLS. ICC and SLS criteria yielded a false positive rate of 24.4% and 7.7%, respectively when compared to TEE. Although both grading scales provide agreement as to any shunt presence, using the Spencer Scale grade III or higher can decrease by one-half the number of false positive TCD diagnoses to predict large RLS on TEE.


Multiple lysine mutations in the C-terminus of p53 make it resistant to degradation mediated by MDM2 but not by human papillomavirus E6 and induce growth inhibition in MDM2-overexpressing cells.
We have recently shown that lysine mutations in p53's putative C-terminal acetylation sites result in increased stability and cytoplasmic distribution of the p53 protein in a human lung cancer cell line. In the present study, we showed that when lysine residues 372, 373, 381, and 382 of p53 were substituted with alanine, the resulting A4 protein was resistant to MDM2-mediated proteosomal degradation but was highly sensitive to human papillomavirus E6-mediated proteolysis. When A4 and wild-type p53 were transfected into MDM2-overexpressing MCF-7 cells, A4 significantly reduced colony formation in vitro, when compared with wild-type p53. Our results suggest that A4 exerts a growth-inhibitory effect more efficiently than wild-type p53 does in cell lines that overexpress MDM2 and may therefore be a better therapeutic tool than wild-type p53 for certain cancers in which MDM2 is amplified or overexpressed.


Immunocytochemical localization of monoamine oxidase type B in enterochromaffin-like cells of rat oxyntic mucosa.
We used immunohistochemistry to identify the localization of monoamine oxidase type B (MAOB) in the rat oxyntic mucosa. At light microscopic levels, MAOB-immunopositive cells were mostly located in the basal half of the oxyntic mucosa. By a double-labeling immunofluorescence method, it was shown that MAOB immunoreactivity was localized in almost all of histidine decarboxylase (HDC)-positive cells. Only a few MAOB-positive cells were negative for HDC. At electron microscopic levels, immunohistochemical reaction products of MAOB were detected on the mitochondrial outer membranes in cells that showed morphological characteristics of enterochromaffin-like (ECL) cells. These findings indicate that ECL cells contain MAOB in the rat. We provide a hypothesis that MAOB is involved in the inactivation mechanism of histamine that is released from ECL cells and activates parietal cells to secrete gastric acid.


Review of the literature: PCA3 for prostate cancer risk assessment and prognostication.
Prostate cancer antigen 3 (PCA3) is a novel urine-based prostate cancer biomarker that has recently been studied extensively for the prediction of prostate biopsy results and treatment outcomes. Numerous studies have demonstrated that urinary PCA3 scores are predictive of prostate cancer detection on both initial and repeat biopsy. There is conflicting evidence on the relationship between PCA3 with aggressive tumor features and treatment outcomes. This article reviews the current evidence on PCA3 as a marker for prostate cancer detection and prognosis.


[The effect of polychlorinated biphenyls (PCB) on chickens: the effect of long-term administration of medium doses of Delor 103 on the levels of thyroxine, triiodothyronine and total calcium in the blood serum].
A trial with the continual administration of feed contaminated with the Delor 103 preparation (polychlorinated biphenyls--PCB) at a rate of 75 mg per kg for chicks lasted four weeks. The concentrations of serum thyroxine and triiodothyronine were found to decrease, the concentrations of total calcium increased and at the Delor 103 doses of 150 mg per kg even the phosphorus concentration and the activity of alkaline phosphatase in the serum of chicks decreased. The addition of potassium iodide to feed (250 mg per kg) did not influence the clinical picture of Delor 103 intoxication. The results confirm a finding that in the course of PCB intoxication severe disorders of the thyroid gland take place and calcium metabolism is disturbed. This finding is important in view of evaluation of the intoxication of young, growing chicks.


Autistic traits associated with dichotomic thinking mediated by intolerance of uncertainty.
A recent cognitive model suggests that autistic individuals may experience dichotomous thinking patterns mediated by intolerance of uncertainty; however, empirical evidence to support this model is lacking. This study aimed to identify the relationships between autistic traits, intolerance of uncertainty, and dichotomous thinking using the Autism Spectrum Quotient, Short Intolerance of Uncertainty Scale, and the Dichotomous Thinking Inventory. We collected data from non-clinical university students (N = 151; pilot study) and general adults (N = 500; main study) and analyzed the results using structural equation modeling. Both studies showed a significant indirect effect of autistic traits on dichotomous thinking mediated by intolerance of uncertainty. Moreover, the results indicated that intolerance of uncertainty was significantly and positively associated with Autism Spectrum Quotient and Dichotomous Thinking Inventory scores. Conversely, there was a significant negative direct association between Autism Spectrum Quotient and Dichotomous Thinking Inventory scores. This is the first study to demonstrate that autistic traits can result in dichotomous thinking through intolerance of uncertainty. These findings provide insight into the cognitive patterns of autistic individuals.


Calmodulin kinase II constitutively binds, phosphorylates, and inhibits brush border Na+/H+ exchanger 3 (NHE3) by a NHERF2 protein-dependent process.
The epithelial brush border (BB) Na(+)/H(+) exchanger 3 (NHE3) accounts for most renal and intestinal Na(+) absorption. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) inhibits NHE3 activity under basal conditions in intact intestine, acting in the BB, but the mechanism is unclear. We now demonstrate that in both PS120 fibroblasts and polarized Caco-2BBe cells expressing NHE3, CaMKII inhibits basal NHE3 activity, because the CaMKII-specific inhibitors KN-93 and KN-62 stimulate NHE3 activity. This inhibition requires NHERF2. CaMKIIγ associates with NHE3 between aa 586 and 605 in the NHE3 C terminus in a Ca(2+)-dependent manner, with less association when Ca(2+) is increased. CaMKII inhibits NHE3 by an effect on its turnover number, not changing surface expression. Back phosphorylation demonstrated that NHE3 is phosphorylated by CaMKII under basal conditions. This overall phosphorylation of NHE3 is not affected by the presence of NHERF2. Amino acids downstream of NHE3 aa 690 are required for CaMKII to inhibit basal NHE3 activity, and mutations of the three putative CaMKII phosphorylation sites downstream of aa 690 each prevented KN-93 stimulation of NHE3 activity. These studies demonstrate that CaMKIIγ is a novel NHE3-binding protein, and this association is reduced by elevated Ca(2+). CaMKII inhibits basal NHE3 activity associated with phosphorylation of NHE3 by effects requiring aa downstream of NHE3 aa 690 and of the CaMKII-binding site on NHE3. CaMKII binding to and phosphorylation of the NHE3 C terminus are parts of the physiologic regulation of NHE3 that occurs in fibroblasts as well as in the BB of an intestinal Na(+)-absorptive cell.


Pulmonary Manifestations of Hematologic and Oncologic Diseases in Children.
Pulmonary complications are common in children with hematologic or oncologic diseases, and many experience long-term effects even after the primary disease has been cured. This article reviews pulmonary complications in children with cancer, after hematopoietic stem cell transplant, and caused by sickle cell disease and discusses their management.


Effect of anabolic steroids on rat heart muscle cells. I. Intermediate filaments.
Long-term treatment of female rats with the anabolic steroid hormone Methandrostenolone results in a conspicuous increase of intermediate sized, nonmyofibrillar filaments in muscle cells of the left cardiac ventricle, as revealed by electron microscopy. These filaments, measuring 70 - 110 A in diameter, form a characteristic network at the Z-level of the sarcomere, either encircling or penetrating the Z-bands, and appear to insert into the nuclear membrane. The T-system is accompanied by the filaments adjacent to the site of the couplings. Here they are attached to subsarcolemmal electron-dense patches, which may be Z-line precursor material. The filaments may function as a cytoskeleton, to provide passive support in the mechanism of contraction and to mediate nucleo-sarcolemmal and nucleo-myofibrillar exchange.


Apaf1 inhibition promotes cell recovery from apoptosis.
The protein apoptotic protease activating factor 1 (Apaf1) is the central component of the apoptosome, a multiprotein complex that activates procaspase-9 after cytochrome c release from the mitochondria in the intrinsic pathway of apoptosis. We have developed a vital method that allows fluorescence-activated cell sorting of cells at different stages of the apoptotic pathway and demonstrated that upon pharmacological inhibition of Apaf1, cells recover from doxorubicin- or hypoxia-induced early apoptosis to normal healthy cell. Inhibiting Apaf1 not only prevents procaspase-9 activation but delays massive mitochondrial damage allowing cell recovery.


Unilateral agenesis of the diaphragm.
During a period of 4 1/2 years, 37 infants with congenital diaphragmatic hernia were treated. The overall survival rate was 68%. Survival depended more on cardiopulmonary function than the size of the diaphragmatic defect. There was little evidence that infants with agenesis of the diaphragm formed a special group with a poor prognosis, and four of the ten patients with unilateral agenesis survived. A Dacron prosthesis is recommended as a substitute for the missing diaphragm.


Camptocormia as the presenting symptom in sporadic late onset nemaline myopathy: a case report.
Camptocormia has been reported in a plethora of diseases comprising disorders of the central nervous system, the peripheral nervous system, and the neuromuscular junction as well as hereditary and acquired myopathies. In sporadic late onset nemaline myopathy concomitant axial myopathy is common, but reports about camptocormia as the only presenting symptom in this condition are very rare. Notably, sporadic late onset nemaline myopathy is a potentially treatable condition in particular when associated with monoclonal gammopathy of unknown significance, HIV or rheumatological disorders. We report the case of a 62-year-old female patient, who presented with slowly progressive camptocormia. Comprehensive work-up including neurological work-up, laboratory tests, MR-imaging, muscle biopsy and genetic testing led to the diagnosis of sporadic late onset nemaline myopathy. Our case report highlights that sporadic late onset nemaline myopathy has to be considered in patients presenting with isolated camptocormia and comprehensive work-up of camptocormia is mandatory to ascertain the individual diagnosis, especially in consideration of treatable conditions.


Photon-Counting CT of the Brain: In Vivo Human Results and Image-Quality Assessment.
Photon-counting detectors offer the potential for improved image quality for brain CT but have not yet been evaluated in vivo. The purpose of this study was to compare photon-counting detector CT with conventional energy-integrating detector CT for human brains. Radiation dose-matched energy-integrating detector and photon-counting detector head CT scans were acquired with standardized protocols (tube voltage/current, 120 kV(peak)/370 mAs) in both an anthropomorphic head phantom and 21 human asymptomatic volunteers (mean age, 58.9 ± 8.5 years). Photon-counting detector thresholds were 22 and 52 keV (low-energy bin, 22-52 keV; high-energy bin, 52-120 keV). Image noise, gray matter, and white matter signal-to-noise ratios and GM-WM contrast and contrast-to-noise ratios were measured. Image quality was scored by 2 neuroradiologists blinded to the CT detector type. Reproducibility was assessed with the intraclass correlation coefficient. Energy-integrating detector and photon-counting detector CT images were compared using a paired t test and the Wilcoxon signed rank test. Photon-counting detector CT images received higher reader scores for GM-WM differentiation with lower image noise (all P < .001). Intrareader and interreader reproducibility was excellent (intraclass correlation coefficient, ≥0.86 and 0.79, respectively). Quantitative analysis showed 12.8%-20.6% less image noise for photon-counting detector CT. The SNR of photon-counting detector CT was 19.0%-20.0% higher than of energy-integrating detector CT for GM and WM. The contrast-to-noise ratio of photon-counting detector CT was 15.7% higher for GM-WM contrast and 33.3% higher for GM-WM contrast-to-noise ratio. Photon-counting detector brain CT scans demonstrated greater gray-white matter contrast compared with conventional CT. This was due to both higher soft-tissue contrast and lower image noise for photon-counting CT.


Sepsis rates in hip replacement surgery with special reference to the use of ultra clean air.
A study is reported of sepsis rates in 836 total hip replacements carried out in various physical environments including ultra-clean air. In a further sutdy the bacteriology of the air around the wound and of the wound itself was investigated during the course of 32 joint replacement operations with and without ultra-clean air. Bacteriological contamination of the air was markedly reduced by the use of ultra-clean air but the wounds themselves were no cleaner than with conventional air conditioning provided that unsterile personel were kept at least Imetri away from the sterile area. The sepsis rate was high at the outset of the study (when a physically apalling theatre was in use, the operative technique was novel and prophylactic antibiotics were not employed). Thereafter it fell and remained unchanged in spite of the introduction of ultra-clean air. We conclude that the efficacy of techniques amiced at sterilizing the air around the wound may now be unprovable in view of the low sepsis rates which can be obtained in a conventional environment. Our results do however show that unsterile personel should not be allowed to approach within Imetri of the sterile area, whatever venitlation is employed.


Targeting PUF60 prevents tumor progression by retarding mRNA decay of oxidative phosphorylation in ovarian cancer.
Ovarian cancer (OC) is the leading cause of death from gynecological malignancies, and its etiology and pathogenesis are currently unclear. Recent studies have found that PUF60 overexpressed in various cancers. However, the exact function of PUF60 in global RNA processing and its role in OC has been unclear. The expression of PUF60 and its relationship with clinical characteristics were analyzed by multiple database analysis and immunohistochemistry. Phenotypic effects of PUF60 on ovarian cancer cell proliferation and metastasis were examined by in vitro cell proliferation assay, migration assay, and in vivo xenograft models and lung metastasis models. RNA immunoprecipitation, seahorse analyses, RNA stability assay were used to study the effect of PUF60 on the stability of oxidative phosphorylation (OXPHOS)-related genes in OC. We report PUF60 is highly expressed in OC with frequent amplification of up to 33.9% and its upregulation predicts a poor prognosis. PUF60 promotes the proliferation and migration of OC cells both in vitro and in vivo. Mechanistically, we demonstrated that silencing of PUF60 enhanced the stability of mRNA transcripts involved in OXPHOS and decreased the formation of processing bodies (P-bodies), ultimately elevating the OXPHOS level. Our study unveils a novel function of PUF60 in OC energy metabolism. Thus, PUF60 may serve as a novel target for the treatment of patients with OC.


Are we missing reverse TRALI? - A real world experience from a tertiary care oncology centre in India.
Transfusion related acute lung injury (TRALI) is a rare but potentially fatal pulmonary complication of transfusion that presents as acute hypoxemia and non-cardiogenic pulmonary oedema, developing during or within six hours of transfusion. Majority of the cases reported are due to transfusion of plasma rich blood components containing antibodies to human leukocyte antigen (anti-HLA) or human neutrophil antigen (anti-HNA). Rarely, anti-HLA or anti-HNA in recipients against transfused donor leukocyte antigens, cause TRALI by a reverse mechanism. Herein, we report three cases of suspected TRALI following transfusions of buffy coat derived granulocytes and peripheral blood stem cells. Three patients with hematological malignancies developed pulmonary symptoms after transfusions of leukocyte rich blood components. All cases showed findings of bilateral pulmonary infiltrates at chest radiography and patients were managed accordingly; however, all three expired within seven days of transfusion due to progressive respiratory deterioration. The patients were transfusion dependent for a long time and had received multiple non-leukoreduced blood components in the past. Clinical findings in all three cases indicate the possibility of reverse TRALI. Although, patients' anti-HLA or anti-HNA antibodies concordance with donors' cognate antigens (HLA and HNA) was not confirmed; yet these three cases suggest that reverse pathogenesis of TRALI is not as infrequent as reported in the literature. However, reverse TRALI has not been confirmed as the presence and nature of antibodies in the transfused recipient were not investigated due to the non availability of immunodiagnostic tests in India.


TACI Constrains TH17 Pathogenicity and Protects against Gut Inflammation.
TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) plays critical roles in B cells by promoting immunoglobulin class switching and plasma cell survival. However, its expression and function in T cells remain controversial. We show here that TACI expression can be strongly induced in murine CD4+ T cells in vitro by cytokines responsible for TH17 but not TH1 or TH2 differentiation. Frequencies and numbers of TH17 cells were elevated in TACI-/ - compared with wild-type mice as well as among TACI-/ - versus wild-type CD4+ T cells in mixed bone marrow chimeras, arguing for a T cell-intrinsic effect in the contribution of TACI deficiency to TH17 cell accumulation. TACI-/ - mice were more susceptible to severe colitis induced by dextran sodium sulfate or adoptive T cell transfer, suggesting that TACI negatively regulates TH17 function and limits intestinal inflammation in a cell-autonomous manner. Finally, transcriptomic and biochemical analyses revealed that TACI-/ - CD4+ T cells exhibited enhanced activation of TH17-promoting transcription factors NFAT, IRF4, c-MAF, and JUNB. Taken together, these findings reveal an important role of TACI in constraining TH17 pathogenicity and protecting against gut disease.


Bacteriophages of freshwater Brevundimonas vesicularis isolates.
Nine strains of Brevundimonas vesicularis were isolated from surface water of three ponds in Bielefeld, Germany. With those strains as indicators seven bacteriophages with different host ranges were isolated. Molecular characterization showed that all phages contained linear double-stranded DNA with a similar genome size of about 37 kb. Restriction analysis and hybridization of phage DNAs revealed that three of these phages are closely related to each other. These phages had morphologies typical of the family Siphoviridae. Their genomes contained cohesive ends. Four phages were classified into the family of Podoviridae. Restriction analysis of the DNAs of these phages did not reveal any similarities. The DNA of these phages were terminally redundant. All phages were unable to transduce plasmids or marker genes.


[Analysis of the changes observed in the sleep EEG recording of patients with juvenile myoclonic epilepsy].
The initial phases and transitional periods of sleep facilitate electroclinical manifestations of juvenile myoclonic epilepsy (JME). The period at the time of waking is identified in the different phases of sleep by cyclic electrophysiological oscillations, which in turn are synchronous with the spike-and-wave or multiple spike-and-wave activity of the electric crises seen in JME and other epileptic syndromes. This observation supports the theory of an alternating cyclical pattern (ACP) as the trigger of these discharges. Following classical macrostructural and microstructural patterns of EEG sleep analysis, we investigated electrophysiological behavior in 13 patients diagnosed as having JME, and 5 persons of homogeneous epidemiological characteristics as controls. In our study we observed that both groups had similar macrostructural sleep parameters. However, in patients prone to crises, these were concentrated in the first two hours recorded and showed no differences in sleep-waking transition or ACP of phase I sleep. These were significant when both periods were compared with the remaining NREM sleep. We conclude from this study that ACP is the microstructural element of sleep which modulates and permits classification of epileptiform anomalies, mainly in studies at the time of wakening.


Neurotoxicological Profiling of Paraquat in Zebrafish Model.
Paraquat is a polar herbicide protecting plant products against invasive species, it requires careful manipulation and restricted usage because of its harmful potentials. Exposure to paraquat triggers oxidative damage in dopaminergic neurons and subsequently causes a behavioral defect in vivo. Thereby, persistent exposure to paraquat is known to increase Parkinson's disease risk by dysregulating dopaminergic systems in humans. Therefore, most studies have focused on the dopaminergic systems to elucidate the neurotoxicological mechanism of paraquat poisoning, and more comprehensive neurochemistry including histaminergic, serotonergic, cholinergic, and GABAergic systems has remained unclear. Therefore, in this study, we investigated the toxicological potential of paraquat poisoning using a variety of approaches such as toxicokinetic profiles, behavioral effects, neural activity, and broad-spectrum neurochemistry in zebrafish larvae after short-term exposure to paraquat and we performed the molecular modeling approach. Our results showed that paraquat was slowly absorbed in the brain of zebrafish after oral administration of paraquat. In addition, paraquat toxicity resulted in behavioral impairments, namely, reduced motor activity and led to abnormal neural activities in zebrafish larvae. This locomotor deficit came with a dysregulation of dopamine synthesis induced by the inhibition of tyrosine hydroxylase activity, which was also indirectly confirmed by molecular modeling studies. Furthermore, short-term exposure to paraquat also caused simultaneous dysregulation of other neurochemistry including cholinergic and serotonergic systems in zebrafish larvae. The present study suggests that this neurotoxicological profiling could be a useful tool for understanding the brain neurochemistry of neurotoxic agents that might be a potential risk to human and environmental health.


Red blood cell distribution width to platelet ratio predicts early neurological deterioration in acute ischemic stroke patients receiving intravenous thrombolysis.
Inflammation plays a prominent role in the pathogenesis and progression of acute ischemic stroke (AIS). The red blood cell distribution width to platelet ratio (RPR) has been demonstrated as a novel biomarker to indicate the severity of inflammatory reaction. This study aimed to explore the association between RPR before intravenous thrombolysis and early neurological deterioration (END) after thrombolysis in AIS patients. AIS patients accepting intravenous thrombolysis were recruited continuously. Postthrombolysis END was defined as death or an increase in the National Institute of Health Stroke Scale (NIHSS) score ≥4 points within 24 h after intravenous thrombolysis compared to the NIHSS score before intravenous thrombolysis. We constructed univariate and multivariate logistic regression analyses to investigate the relationship of RPR before intravenous thrombolysis to postthrombolysis END. Moreover, a receiver operating characteristic (ROC) curve was applied to examine the discriminative utility of RPR before intravenous thrombolysis in predicting postthrombolysis END. A total of 235 AIS patients were included, and 31 (13.19%) subjects underwent postthrombolysis END. The univariate logistic regression analysis demonstrated that RPR before intravenous thrombolysis was significantly related to postthrombolysis END (odds ratio [OR], 2.162; 95% confidence interval [CI], 1.605-2.912; P < 0.001). After adjusting for potential confounding variables with P < 0.15 in the univariate logistic regression analysis, the difference remained statistically significant (OR, 2.031; 95% CI, 1.436-2.873; P < 0.001). Furthermore, an optimal cutoff value of 7.66 for RPR before intravenous thrombolysis in predicting postthrombolysis END was observed in the ROC curve analysis, and the sensitivity and specificity were calculated as 61.3% and 81.9%, respectively (area under the curve [AUC], 0.772; 95% CI, 0.684-0.860; P < 0.001). RPR before intravenous thrombolysis might be an independent risk factor for postthrombolysis END in AIS patients. Elevated levels of RPR before intravenous thrombolysis may predict postthrombolysis END.


[The Erlangen examination. An alternative to multiple choice testing for German neurology students].
With the latest revision of the German Medical Licensing Regulation in 2002, educating faculties gained more freedom in the organisation and assessment of trainees. The Erlangen Neurological Exam Structured (ERNEST) is an alternative for assessing competency in clinical knowledge at the end of the neurological general education. The answers must be given in written, short essay format. The students (mostly 5th year of medical education) underwent the ERNEST including eight sections with ten to 15 questions each and the MC examination as had been applied earlier. The results were given in percentage scores. The examination was evaluated by a questionnaire using Likert scales. A total of 128 students (81 women, 47 men) with a mean age of 25.3 years (range 22-33) completed their initial training by the exam. The mean score was 69.6% in the ERNEST and 73.4% in the MC part (P<0.001). Of the students 12.5% in ERNEST and 11.7% in the MC (nonsignificant) failed to reach the projected score of 60% to pass the exam. Correlation between the ERNEST and MC results was significant, with r=0.784 (Pearson's coefficient, P<0.001). The students evaluated the aspects innovation, length, format, clarity of the tasks, closeness to reality, and compatibility with general physician's practice as predominantly positive. The ERNEST is a viable alternative form of assessment as compared to the conventional MC exam. The basic quantitative parameters of the assessment comply with the requirements of medical assessments. The students evaluated ERNEST as mainly positive.


Distinct Laminar Processing of Local and Global Context in Primate Primary Visual Cortex.
Visual perception is affected by spatial context. In visual cortex, neuronal responses to stimuli inside the receptive field (RF) are suppressed by stimuli in the RF surround. To understand the circuits and cortical layers processing spatial context, we simultaneously recorded across all layers of macaque primary visual cortex while presenting stimuli at increasing distances from the recorded cells' RF. We find that near versus far-surround stimuli activate distinct layers, thus revealing unique laminar contributions to the processing of local and global spatial context. Stimuli in the near-surround evoke the earliest subthreshold responses in superficial and upper-deep layers, and earliest suppression of spiking responses in superficial layers. Conversely, far-surround stimuli evoke the earliest subthreshold responses in feedback-recipient layer 1 and lower-deep layers, and earliest suppression of spiking responses almost simultaneously in all layers, except 4C, where suppression emerges last. Our results suggest distinct circuits for local and global signal integration.


Molecular mechanisms that regulate the heat stress response in sea urchins (Strongylocentrotus intermedius) by comparative heat tolerance performance and whole-transcriptome RNA sequencing.
In the context of climate change and extreme high temperature, the commercially important sea urchin Strongylocentrotus intermedius suffers high mortality during summer in Northern China. How sea urchins respond to high temperatures is of great concern to academia and industry. How to understand the heat tolerance of sea urchin from the whole transcriptome level. In this study, the heat-resistant S. intermedius bred by our team and its control group were used as the research objects, then we applied whole-transcriptome RNA sequencing to detect differentially expressed mRNAs, microRNAs, long noncoding RNAs that respond to heat stress in the heat-resistant and control S. intermedius. A competitive endogenous RNA (ceRNA) regulatory network was constructed with predicted pairs of differentially expressed mRNAs and noncoding RNAs and revealed the molecular regulatory mechanisms in S. intermedius responding to heat stress. A functional analysis suggested that the ceRNAs were involved in basal metabolism, calcium ion transport, endoplasmic reticulum stress, and apoptosis. This is the whole-transcriptomic analysis of S. intermedius under heat stress to propose ceRNA networks that will provide a basis for studying the potential functions of long noncoding RNAs and miRNAs in the heat stress response in S. intermedius and provide a theoretical basis for the study of the molecular mechanism of sea urchins in response to environmental changes.


Comparison of the performance of two real-time fluorescent quantitative PCR kits for the detection of SARS-CoV-2 nucleic acid: a study based on large real clinical samples.
The global pandemic of coronavirus disease 2019 (COVID-19) has led to the development of multiple detection kits by national manufacturers for severe acute respiratory syndrome coronavirus 2 viral nucleic acid testing. The purpose of this study is to evaluate the performance of different kits (i.e., Maccura kit and Sansure kit) in real clinical work using clinical samples, which will help with the optimization of the test kits. During the past three months (March-May 2022), 1399 pharyngeal swabs from suspected COVID-19 patients have been initially screened using the Maccura kit in Jilin, China, and the test results were verified using the Sansure kit. The cycle threshold (Ct) values generated by the two kits were compared at different viral load levels. Correlation and consistency of the Ct values were investigated using Spearman correlation, Deming regression, and Bland-Altman plots. The cut-off Ct values of the Maccura kit were recalculated by referencing the result of the Sansure kit as a standard. Furthermore, another 163 pharyngeal swabs from suspected COVID-19 patients were collected to verify the new cut-off values. As a result of the Maccura kit testing, 1192 positive cases and 207 suspected COVID-19 cases were verified. After re-examination by the Sansure kit, 1118 positive cases were confirmed. The difference between the Ct values provided by the two kits was statistically significant, except for the N gene at high viral load. The Ct values obtained from the two kits presented a linear positive correlation. The Maccura kit used new cut-off Ct values of 35.00 (ORF1ab gene) and 35.07 (N gene). Based on that, the validation pass rate for the new cut-off Ct values was 91.41%. Since the Maccura kit is found to have false positives in actual clinical work, recalculation of the cut-off values can reduce this occurrence. In order to improve the accuracy of the testing, laboratories should use two kits for COVID-19 testing, and the adjusting and optimizing of the kits for their situation are needed.


Cheyne-Stokes respiration due to chronic heart failure abates with coronary artery revascularization.
A 78-year-old man presented with dyspnea and mild heart failure with Cheyne-Stokes respiration (CSR). Workup revealed inferolateral ischemia in the setting of significant triple vessel coronary disease, and nil else to adequately explain his dyspnea and eventual respiratory failure. After he underwent surgical revascularization, his ventricular function improved, leading to resolution of his respiratory failure and, of interest, his CSR. CSR is a central sleep apnea common in heart failure patients and has been associated with increased mortality. Here, we present the first English-literature report of CSR abating with surgical coronary revascularization, and briefly review the literature.


Effects of high doses of manganese on carbohydrate homeostasis.
The effects of manganese (Mn) toxicity on carbohydrate homeostasis was examined in Sprague-Dawley and Osborne-Mendel rats. Mn injection was followed by increases in Mn concentration in both liver and pancreas. Concentrations of Mn in the pancreas increased more rapidly than in the liver. Plasma insulin levels decreased, plasma glucose levels increased, and a spike in glucagon concentration was observed following Mn injection. Increases in blood glucose in response to Mn injection were also observed in 24- and 48-h fasted rats, although the magnitude of the increase was less than that observed in fed rats. Both strains of rats appeared to respond similarly to Mn injection. The present studies demonstrate that acute Mn injection can affect glucose homeostasis. These effects may be mediated through altered endocrine pancreatic function.


Persistence of gastric ulcers caused by plain aspirin or nonsteroidal antiinflammatory agents in patients treated with a combination of cimetidine, antacids, and enteric-coated aspirin.
Twenty-three patients chronically ingesting plain aspirin or nonsteroidal antiinflammatory drugs, who had endoscopically proven solitary or multiple gastric ulcers, were treated for eight weeks with cimetidine and antacids. Plain aspirin and nonsteroidal antiinflammatory drugs were discontinued in all patients. Seven patients received enteric-coated aspirin throughout the treatment phase and continuously for the entire study period (2.5-12 months). The remainder of patients (N = 16) did not receive enteric-coated aspirin. An endoscopy was performed to assess ulcer healing. None of seven patients receiving enteric-coated aspirin had complete healing of their ulcer(s) while 15 of 16 patients not receiving enteric-coated aspirin demonstrated complete healing of their ulcer(s) (P less than 0.001). An eight-week course of cimetidine and antacids is ineffective in completely healing gastric ulcers caused by plain aspirin or nonsteroidal antiinflammatory drugs while enteric-coated aspirin is continued.


Straatsma Syndrome: Should Visual Prognostic Factors Be Taken into Account? A Case Report.
Straatsma syndrome is the triad of myelinated retinal nerve fibers, myopia, and amblyopia and may be associated with strabismus, nystagmus, hypoplastic optic nerve, and heterochromia iridum. The degree of anisometropia, presence of strabismus, extent of myelination, and macular involvement have been reported to be associated with poor visual acuity after occlusion therapy for amblyopia in this syndrome. Here we present two cases of Straatsma syndrome with different responses to occlusion therapy and discuss their treatment responses according to prognostic factors for post-occlusion visual acuity.


Evidence that the Thy-1 molecule is the target for T cell mitogenic antibody against brain-associated antigens.
Rabbit anti-mouse brain (RaMBr) antiserum can induce Lyt-1+, Lyt-2-, T cells to proliferate and stimulates the same T cell subset to induce B cell proliferation. The aim of this report is to demonstrate that the mitogenic determinant recognized on the T cell surface by RaMBr antiserum is located on the Thy-1 molecule expressing the products of the Thy-1a and Thy-1b alleles. Evidence is drawn from serological and genetic experiments. The brain T cell cross-reactive, mitogenic determinant is not expressed on Thy-1- mutants of the BW5147 T cell lymphoma that fail to express the Thy-1 molecule but do express other T cell surface proteins such as T-200 and gp 69, 71. Monoclonal anti-Thy-1.1 and anti-Thy-1.2 antibodies block the binding to the appropriate T cells of the majority of the serum antibody from RaMBr antiserum. The absorption of mitogenic antibody was blocked in a similar fashion, thus demonstrating the close association of the determinant and the Thy-1 antigen defined by monoclonal alloantibodies. The mitogenic and Thy-1.1 determinants are probably located on the same molecule because of the data obtained with the BW5147 Thy-1- mutants and the observation that Thy-1a T cells, which express a lower level of surface Thy-1 than Thy-1b T cells, also express lower levels of the determinant recognized by RaMBr antiserum. Furthermore, in (AKR x DBA/2)F1 mice (Thy-1a/b) which express less Thy-1.1 antigen than Thy-1.2 at the surface, the mitogenic determinant was found to be preferentially associated with Thy-1.2. The coordinated genetic control of the surface levels of the Thy-1 determinant and the mitogenic determinant suggests that both determinants are situated on the same molecule in the T cell membrane.


Cephalometric findings among children with velopharyngeal dysfunction following adenoidectomy-A retrospective study.
To characterise the craniofacial structure by cephalometry, especially the skull base and nasopharyngeal space, in children who underwent adenoidectomy and developed persistent velopharyngeal dysfunction (VPD). Retrospective study. Speech and swallowing clinic of a single academic hospital. Thirty-nine children with persistent VPD following adenoidectomy (mean age 8.0±3.6 years) and a control group of 80 healthy children. Cephalometric landmarks were chosen; craniofacial linear and angular dimensions were measured and analysed. The linear dimensions of the nasopharyngeal area were shorter in the VPD group, S-Ba (41.6±4.2 mm, P<.05) and S-Ptm (42.4±5.1 mm, P<.05). The anterior skull base, N-S, was similar (68.1 mm±6.8). The velum length, Ptm-P was significantly shorter in the VPD group (27.8±4.3 mm, P<.001). The Ba-S-Ptm angle was significantly larger in the VPD group (63.5±5.6°, P<.001). There was no significant difference in cranial base angle (CBA), Ba-S-N, between the two groups. Cephalometry may provide information regarding persistent postoperative VPD. The nasopharyngeal space angle and velar length appear to be risk factors for persistent VPD after adenoidectomy.


Barriers to discontinuing antidepressants in patients with depressive and anxiety disorders: a review of the literature and clinical recommendations.
Use of antidepressants has recently increased, mainly caused by the increase of long-term users. Although evidence-based indications for long-term use are lacking, it is assumed that long-term use is unnecessary or undesirable in some patients. Perceived barriers to discontinuing antidepressants contribute to unnecessary or undesirable long-term use. Identifying barriers prior to, during and following discontinuation may enable strategies to overcome them. This narrative review summarises relevant qualitative and quantitative articles on perceived barriers to discontinuing antidepressants and provides recommendations for clinical practice. We can conclude that implications for clinical practice are diverse and the most important barriers experienced by patients and physicians include the fear of relapse or recurrence, insufficient evaluation and monitoring, withdrawal symptoms, and actual relapse or recurrence.


Usefulness of a rapid human immunodeficiency virus-1 antibody test for the management of occupational exposure to blood and body fluid.
To describe the usefulness of the OraQuick Rapid HIV-1 Antibody Test (OraSure Technologies, Bethlehem, PA) in cases of occupational exposure regarding its use with source-patient sera, effects on post-exposure prophylaxis (PEP) use, potential cost savings, and effects on healthcare worker (HCW) stress reaction symptoms. Before-and-after analysis. A 269-bed, tertiary-care medical center with adjacent clinics. All source-patients and HCWs experiencing an occupational exposure during the study period. Use of the OraQuick test with patient sera was validated prior to its use for occupational exposures. Exposures from January 1 through July 10, 2003 (enzyme immunoassay [EIA] group) and July 11 through December 31, 2003 (OraQuick group) were retrospectively reviewed and the use and cost of PEP was compared for each group. Randomly selected HCWs from both groups completed a survey to assess their stress reaction symptoms. After exclusion, there were 71 exposures in the EIA group and 79 in the OraQuick group. OraQuick results were 100% concordant with the reference standard of EIA and Western blot using patient sera. The mean number of doses ingested per course of PEP was significantly higher for HCWs in the EIA group (3.8; range, 0 to 6) compared with the OraQuick group (1.2; range, 0 to 3; P = .016). Cost analysis revealed a mean savings of dollar 6.62 with the OraQuick test per occupational exposure. Although the survey failed to detect an overall reduction in HCW stress reaction symptoms using OraQuick for source-patient testing, 11 HCWs in the EIA group had repetitive thoughts of the exposure compared with 5 in the OraQuick group (P = .049). Because of the reduction in ingested doses of unnecessary PEP and reduced cost of occupational exposure management with their use, rapid HIV-antibody tests should be the preferred method for source-patient testing following an occupational exposure.


Protein stabilization with a dipeptide-mimic triazine-scaffolded synthetic affinity ligand.
Protein stabilization was achieved by a novel approach based on the adsorption and establishment of affinity-like interactions with a biomimetic triazine-scaffolded ligand. A synthetic lead compound (ligand 3'/11, K(a) ≈ 10(4) M(-1)) was selected from a previously screened solid-phase library of affinity ligands for studies of adsorption and stabilization of cutinase from Fusarium solani pisi used as a model system. This ligand, directly synthesized in agarose by a well-established solid-phase synthesis method, was able to strongly bind cutinase and led to impressive half-lives of more than 8 h at 70 °C, and of approximately 34 h at 60 °C for bound protein (a 25- and 57-fold increase as compared with the free enzyme, respectively). The ligand density in the solid matrix was found to be a determinant parameter for cutinase stabilization. It is conceivable that the highly stabilizing effect observed results from the binding of more than one ligand residue to the enzyme, creating specific macromolecular configurations that lock structural mobility thus improving molecular stability.


Sexual trauma is more strongly associated with tonic immobility than other types of trauma - A population based study.
Tonic immobility is an involuntary motor and vocal inhibition reaction, considered the last-ditch response of the defensive cascade model. It is elicited in context of inescapable threat and perception of entrapment. Our aim was to investigate the association between different traumatic events and peritraumatic tonic immobility (PTI) in a representative sample of the general population. This is a cross-sectional study of general population from Rio de Janeiro and São Paulo with 3231 victims of traumatic events aged 15-75 years who completed the Tonic Immobility Scale (TIS). We calculated the frequency of the different traumatic events and estimated the mean scores with 95% confidence intervals for each traumatic event, controlling for the potential confounders using multiple linear regression models. Finally, we calculated the proportion of individual scoring zero in TIS for the 16 traumatic events. PTI scores in child sexual abuse and adult sexual violence were almost twice as high as in other types of traumatic events, even when controlled for gender and educational level. Torture and war also showed high PTI scores, but these were based on very small number of cases and need to be interpreted with caution. Furthermore, victims of sexual trauma had the lowest proportion of individuals with total absence of PTI symptoms. This is a cross-sectional study and causal inferences must be drawn with caution. Peritraumatic tonic immobility is more strongly associated with sexual trauma, particularly in childhood, than to other types of trauma in the general population.


Qué es la Epilepsia? Attitudes and knowledge of epilepsy by Spanish-speaking adults in the United States.
Spanish-speaking adults are the largest minority population group in the United States and are disproportionately afflicted by epilepsy. A unique 78-item survey instrument conducted entirely in Spanish and devoted to the topic of epilepsy was administered to 760 Spanish-speaking adults in seven large U.S. Hispanic metropolitan areas representing a cross section of the U.S. Hispanic community. The answers were compared with those of 272 non-Hispanic controls administered the same survey in English in June 2004. The Hispanic sample correlated well with U.S. Census data. Spanish-speaking adults are mostly unaware about epilepsy, with 21% reporting no familiarity with the condition (P=0.0001). The vast majority of Hispanics use the term convulsiones or ataque to describe a seizure. Thirteen percent of Hispanics with less than high school education believe that epilepsy is contagious (P=0.0001); 8% see "sins" as a cause of seizures (P=0.0001); and 10% agree that "exorcism" would be a good remedy (P=0.002). There is considerable misinformation about epilepsy in the U.S. Hispanic community. Neurologists must be made aware of U.S. Hispanic attitudes and beliefs regarding epilepsy to provide culturally competent care.


Uncontrolled Acute Intermittent Porphyria as a Cause of Spontaneous Abortion.
The association of acute intermitetn porphyria (AIP) with pregnancy and as a cause of spontaneous abortion is rare. To show a case of AIP known before pregnancy in a patient who had a spontaneous abortion. A gynecologist examined 26-year-old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely. Treatment of threatened spontaneous abortion in AIP remains the subject of dilemma and controversy, and future research is needed.


Clinical performance of IPS-Empress 2 ceramic crowns inserted by general dental practitioners.
The aim of this study was to evaluate the clinical performance of IPS-Empress 2(R) all-ceramic crowns placed by general dental practitioners. Eighty-two IPS-Empress 2 crowns placed in 64 patients (27 females and 37 males) were evaluated. These crowns had been in place for 15.2 to 57.2 months (mean 25.3 months, SD=9.3). Survival analysis was conducted using the Kaplan-Meier method. Of the 82 crowns 93.9% were rated satisfactory. In terms of the integrity of the restorations, fracture was observed in three crowns and two showed a crack upon transillumination. Five crowns were rated unsatisfactory for color match; one for marginal adaptation; and none for discoloration, secondary caries, or sensitivity. IPS-Empress 2(R) is a suitable material to fabricate all-ceramic crowns; when these all-ceramic crowns were inserted by general dental practitioners, they functioned satisfactorily with low failure rates during an observation period ranging between 15.2 to 57.2 months.


Analyzing the value of an educational program for psoriasis patients: a prospective controlled pilot study.
Psoriasis is a chronic inflammatory skin disease associated with a reduced life-quality. Severe disease forms put the patients at risk for life-treating cardiovascular events, metabolic, and other immune-mediated disorders. Psoriasis patients are often not sufficiently informed about their condition leading to suboptimal treatment adherence and, consequently, worse patient outcome. We investigated the value of an educational program on knowledge and self-expertise about the disease in psoriasis patients in general and dependent on age and disease duration. Regular visit psoriasis-patients were asked to participate and choose to receive an additional educational program or not. Participating patients (n = 53) filled out two questionnaires: one at study inclusion and one at the next regular visit or after the absolved educational program. Surveys included disease knowledge assessment and numeric rating scales (0-10) for self-expertise about the disease, therapy adherence, and therapy satisfaction. The Dermatology Life Quality Index (DLQI) was used to investigate the quality of life. All continuous parameters were examined for statistically significant differences by paired t-test or unpaired t-test. Continuous parameters without Gaussian distribution were analyzed with the Wilcoxon matched pairs test or the Mann-Whitney test. For all categorical parameters, Fisher's exact test was used. Patients who chose to be educated (n = 24) showed a significant increase in knowledge, self-expertise about the disease and amelioration of general health. No positive short-term effects were seen on the quality of life and therapy adherence. Analyzing the effect of age and disease duration, the educational program led to significant improvement of the emotional well-being in older patients (≥50 years) and with a longer disease duration as well as significant amelioration of the self-expertise about psoriasis in younger patients (< 50 years). Patients who chose to participate in an educational program show a higher gain in knowledge and self-expertise about the psoriatic disease. Educational program thus might have a positive effect on the long-term management of psoriasis. Further long-term studies are needed to provide evidence for the influence educational programs have on outcome, quality of life, and treatment adherence of psoriatic patients. Deutsches Register Klinischer Studien DRKS00017318 (09.10.2019), retrospectively registered.


Turbulent left-to-right shunt flow through the interatrial septum suggesting high left atrial pressure in patients with heart failure with preserved ejection fraction.
Lutembacher's syndrome is a combination of interatrial septal (IAS) defect or patent foramen ovale (PFO), associated with mitral stenosis. High left atrial (LA) pressure in mitral stenosis exaggerates left-to-right shunt in patients with interatrial communication. We present a case of heart failure with preserved ejection fraction. Echocardiography revealed normal left ventricular systolic function without mitral stenosis and turbulent left-to-right shunt through the IAS. The peak velocity of the shunt flow was 2.3 m/s and the estimated pressure gradient was 22 mmHg, indicating high LA pressure. The presence of turbulent left-to-right shunt through the IAS is helpful for detecting high LA pressure.


Screening HLA-A-restricted T cell epitopes of SARS-CoV-2 and the induction of CD8+ T cell responses in HLA-A transgenic mice.
Since severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific T cells have been found to play essential roles in host immune protection and pathology in patients with coronavirus disease 2019 (COVID-19), this study focused on the functional validation of T cell epitopes and the development of vaccines that induce specific T cell responses. A total of 120 CD8+ T cell epitopes from the E, M, N, S, and RdRp proteins were functionally validated. Among these, 110, 15, 6, 14, and 12 epitopes were highly homologous with SARS-CoV, OC43, NL63, HKU1, and 229E, respectively; in addition, four epitopes from the S protein displayed one amino acid that was distinct from the current SARS-CoV-2 variants. Then, 31 epitopes restricted by the HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C), R848 or poly (lactic-co-glycolic acid) nanoparticles, and these vaccines elicited robust and specific CD8+ T cell responses in HLA-A2/DR1 transgenic mice as well as wild-type mice. In contrast to previous research, this study established a modified DC-peptide-PBL cell coculture system using healthy donor PBMCs to validate the in silico predicted epitopes, provided an epitope library restricted by nine of the most prevalent HLA-A allotypes covering broad Asian populations, and identified the HLA-A restrictions of these validated epitopes using competitive peptide binding experiments with HMy2.CIR cell lines expressing the indicated HLA-A allotype, which initially confirmed the in vivo feasibility of 9- or 10-mer peptide cocktail vaccines against SARS-CoV-2. These data will facilitate the design and development of vaccines that induce antiviral CD8+ T cell responses in COVID-19 patients.


Evidence for pH dependent Zn2+influx in K562 erythroleukemia cells: studies using ZnAF-2F fluorescence and 65Zn2+ uptake.
Using both ZnAF-2F (a Zn2+ specific fluorophore) and 65Zn2+, we determined the rate of transporter mediated Zn2+ influx (presumably mediated by the SLC39A1 gene product, protein name hZIP1) under steady state conditions and studied the effects of extracellular acidification. When K562 erythroleukemia cells were placed in Zn2+ containing buffers (1-60 microM), the initial rate of 65Zn2+ accumulation mirrored the apparent rise in free intracellular Zn2+ concentrations sensed by ZnAF-2F. Therefore, newly transported Zn2+ equilibrated with the free intracellular Zn2+ pool sensed by ZnAF-2F. A new steady state with elevated free intracellular Zn2+ was established after about 30 min. An estimate of 11 microM for the Km and 0.203 nmol/mg/s for the Vmax were obtained for Zn2+ influx. 65Zn2+ uptake and ZnAF-2F fluorescent changes were inhibited by extracellular acidification (range tested: pH 8-6, IC50 = pH 6.34). The IC50 for proton effects was close to the pKa for histidine, suggesting conserved histidine residues present in SLC39A1 play a critical role in Zn2+ influx and are involved in the pH effect.