Does entrepreneurship education promote vocational students' entrepreneurial mindset?
This paper aims to explore how entrepreneurship education determines students' entrepreneurial intentions as well as examine the emerging role of the entrepreneurial mindset in supporting this relationship. A quantitative method was applied to gain a better understanding of the relationship between variables utilizing Structural Equation Modeling (SEM) based variance Partial Least Square (PLS). The participants of this study were recruited from several vocational students in East Java of Indonesia by using an online survey. The findings indicate that entrepreneurship education positively influences both students' entrepreneurial intentions and an entrepreneurial mindset. It also reveals a robust correlation between entrepreneurship mindset and students' entrepreneurship intentions. Lastly, this study's finding shows that the entrepreneurship mindset has successfully mediated the relationship between entrepreneurial education and students' entrepreneurial intention.


Dietary Capsaicin Reduces Chemically Induced Rat Urinary Bladder Carcinogenesis.
Capsaicin (CAP) is the compound responsible for pungency in chili peppers, presenting several biological properties. But its general safety and effectiveness in the context of carcinogenesis has not been fully clarified. Thus, the present study evaluated whether dietary CAP modifies the development of urothelial lesions induced by the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in male Sprague-Dawley rats. Animals were randomly allocated into 6 groups: G1 - treated with 0.05% BBN in drinking water (weeks 1-12) and received a balanced diet (weeks 1-20); G2 and G3-treated with BBN (weeks 1-12) and received a balanced diet with 0.01 or 0.02% CAP (weeks 1-20), respectively; G4 and G5- only received a balanced diet with 0.01 or 0.02% CAP (weeks 1-20), respectively; G6 - only received a balanced diet (weeks 1-20). At the end of week 20, the incidence and types of urothelial lesions, proliferating cell nuclear antigen (PCNA) labeling index, and matrix metalloproteinases (MMP) 2 and 9 activities were analyzed. A significant reduction was observed in the incidence and multiplicity of simple (p = 0.020 and p = 0.011) and nodular/papillary (p = 0.030 and p = 0.003) hyperplasias and papillomas/carcinomas (p = 0.023 and p = 0.020), epithelial proliferation (p = 0.007) and in the activity of the intermediate form of MMP-2 (p < 0.001) and pro-MMP-9 activities (p < 0.002), in BBN + 0.02% CAP (G3) group in comparison to BBN (G1) group. Capsaicin intake per se did not alter body weight, liver and kidney weights, urothelial histology or serum biochemical parameters. Thus, dietary CAP was safe and showed a protective effect against rat BBN-induced urothelial carcinogenesis.


Apoptotic effect and cell arrest of deoxyshikonin in human osteosarcoma cells through the p38 pathway.
Osteosarcoma is the most common primary bone cancer that affects adolescents with early metastatic potential and drastically reduces their long-term survival rate if pulmonary metastases are detected at diagnosis. The natural naphthoquinol compound deoxyshikonin exhibits anticancer properties, so we hypothesized that it has an apoptotic effect on osteosarcoma U2OS and HOS cells and studied its mechanisms. After deoxyshikonin treatment, dose-dependent decreases in cell viability, induction of cell apoptosis and arrest in the sub-G1 phase of U2OS and HOS cells were observed. The increases in cleaved caspase 3 expression and the decreases in X-chromosome-linked IAP (XIAP) and cellular inhibitors of apoptosis 1 (cIAP-1) expressions after deoxyshikonin treatment in the human apoptosis array were identified in HOS cells, and dose-dependent expression changes of IAPs and cleaved caspase 3, 8 and 9 were verified by Western blotting in U2OS and HOS cells. Phosphorylation of extracellular signal-regulated protein kinases (ERK)1/2, c-Jun N-terminal kinases (JNK)1/2 and p38 expressions in U2OS and HOS cells was also increased by deoxyshikonin in a dose-dependent manner. Subsequently, cotreatment with inhibitors of ERK (U0126), JNK (JNK-IN-8) and p38 (SB203580) was performed to show that p38 signalling is responsible for deoxyshikonin-induced apoptosis in U2OS and HOS cells, but not via the ERK and JNK pathways. These discoveries demonstrate that deoxyshikonin may be a possible chemotherapeutic candidate to induce cell arrest and apoptosis by activating extrinsic and intrinsic pathways through p38 for human osteosarcoma.


Unexpected metallic foreign bodies on panoramic scans - a narrative review.
The digital panoramic radiograph (orthopantomogram, OPG) is the standard radiographic technique for basic diagnostics in dental practice. A correctly taken image provides a good overview of teeth and jaw, whereas radiopaque foreign materials, e. g. metal, can obscure relevant findings. A literature review on unexpected metallic foreign bodies in OPG was performed to determine the spectrum of metallic foreign bodies that may cause radiopaque areas on panoramic radiographs in routine clinical use. A total of 37 different unexpected metallic foreign bodies were found. They can be categorized as jewelry, clothing, personal protective equipment, medical devices, iatrogenic foreign bodies, and rare incidental findings. Radiopaque foreign materials in the OPG are often relatively easy to recognize as artifacts because of their location, and they are avoidable in most cases. If unclear, a three-dimensional radiograph was helpful for determining the location. Radiopaque areas caused by foreign bodies can lead to misinterpretation or partial or complete non-evaluability and should therefore be avoided. · The OPG is the standard radiograph for dentists, oral surgeons, and oral and maxillofacial surgeons.. · Foreign bodies made of metal can lead to non-evaluability of panoramic radiographs. Based on a review of the literature and exemplary radiographs, this article provides an overview of rare but typical metallic foreign bodies in OPG, thus addressing the problem of the subfield of radiography by making radiologists more familiar with these images.. · The spectrum of unexpected metallic foreign bodies includes unremoved earrings with the typical ghost images on the contralateral side, piercings, hearing aids, acupuncture needles, rare iatrogenic foreign bodies, incidental findings in infants in the nose and external auditory canal, vascular clips after surgical interventions, and ritual subcutaneous foreign materials.. · Brauer HU, Bartols A, Hellmann D et al. Unexpected metallic foreign bodies on panoramic scans - a narrative review. Fortschr Röntgenstr 2023; 195: 809 - 818.


First trimester serum inhibin A in normal pregnant women.
To establish reference ranges for maternal serum inhibin A in normal first trimester pregnant women. This was a cross-sectional study. We measured maternal serum inhibin A in normal pregnant women gestation age between 6(+0) and 14(+6) weeks using the enzyme-linked immunosorbent assay (ELISA) method. Maternal serum inhibin A was analyzed according to gestational ages (GA). Serum of 300 pregnancies was analyzed and the outcome demonstrated the median of maternal serum inhibin A according to gestational age. The levels of maternal serum inhibin A during the 6(0)-6(+6) week of gestations are lowest when compared with other gestational age. The levels of maternal serum inhibin A during 9(0)-9(+6) week of gestations are maximal. Maternal serum inhibin A then declined until 14 weeks of gestation. Serum inhibin A can be measured during the first trimester of pregnancy by using the recent ELISA technique. Our reference ranges might be useful for further studies, such as prediction of adverse pregnancy outcome in threatened abortion.


The use of probes for the Y chromosome in preimplantation embryo cells.
The use of Y chromosome repeated sequence probes for the assignment of sex in individual human and mouse cells by in situ hybridization is described.


Efficacy and adverse event profile of cannabidiol and medicinal cannabis for treatment-resistant epilepsy: Systematic review and meta-analysis.
This paper aimed to systematically examine the efficacy and adverse event (AE) profile of cannabidiol and medicinal cannabis by analyzing qualitative and meta-analytic data. We used the terms ("Cannabidiol" OR "Cannabis") AND "Epilepsy" AND ("Treatment" OR "Therapeutics") as keywords to retrieve studies indexed on PubMed, ScienceDirect, and CENTRAL databases. The inclusion criteria were as follows: clinical studies with a longitudinal observational design and intervention using cannabinoid derivatives, especially cannabidiol and medicinal cannabis, whereby some results involved the frequency of epileptic seizures. We used Cochrane Collaboration's Review Manager software (RevMan 5.1.6) for the meta-analysis and dichotomized the articles to a confidence interval of 95%. From 236 articles, we selected 16 for descriptive analysis; we selected only 4 for the meta-analysis. According to the results, a statistically meaningful effect of cannabidiol compared with placebo was observed (p < 0.00001). When comparing treatment with cannabidiol or medicinal cannabis, significance was not found for the AE profile (p = 0.74). As AEs for cannabidiol were more common under short-term than under long-term treatment (p < 0.00001), this approach was favorable in the long term. Furthermore, cannabidiol is more effective than placebo, regardless of the etiology of epileptic syndromes and dosage. Overall, the AE profile did not differ across treatments with cannabidiol or medicinal cannabis, though it did differ favorably for long-term than for short-term treatment.


Psychological Well-Being, Cognitive Functioning, and Quality of Life in 205 Adolescent and Young Adult Childhood Cancer Survivors Compared to Healthy Peers.
The majority of the studies underlined how adolescent and young adult (AYA) Cancer Survivors had no significant differences in their well-being and quality of life compared with a control group of healthy counterparts, although French et al. (2013) found less years of education among cancer survivors. The present study aimed at comparing AYA cancer survivors and a control group of peers who had no history of serious illness, in terms of well-being, cognitive functioning, and perceptions of life. Participants in this study were 205 AYA cancer survivors, 126 males, off therapy from a mean of 10.87 years (SD = 4.91), with a mean age of 18.96 (SD = 3.08), recruited during follow-up visits and healthy counterparts (n = 205), matched for age and gender. They all completed self-report questionnaires: Ladder of Life, BSI-18 and Cognitive problems. Paired t test evidenced significant differences between survivors (Mean = 6.19; SD = 2.07) and controls (Mean = 6.88; SD = 2.02) in perceptions of quality of life regarding 5 years before the current time [t (204) = -3.39; p = 0.001], with a lower level for childhood cancer survivors. Specifically, Hierarchical regression (R 2 = 0.05, p = 0.04) identified a shorter time since the completion of treatment (β = 0.18, p = 0.03) and a trend of stem cell transplantation experience (β = -0.11, p = 0.06) as factors associated with negative perception of precedent quality of life. The AYA cancer survivors reported lower cognitive difficulties (Mean = 1.46) than controls (Mean = 1.56) [t (204) = -3.41; p = 0.001]: in memory (Meanclinical = 1.32 vs Meancontrol = 1.50) [t (204) = -4.52; p = 0.001], in concentration (Mean clinical = 1.36 vs Meancontrol = 1.54) [t (204) = -4.66; p = 0.001] and in mental organization skills (Mean clinical = 1.47 vs Meancontrol = 1.56) [t (204) = -2.56; p = 0.01], even if they had a lower educational attainment [X ( 9 ) 2 = 131.28; p = 0.001]. They showed similar satisfaction with their psychological well-being and their lives as healthy counterparts, except for past life perceptions associated with the cancer period. Important recommendations for future research and clinical suggestions could be given.


Arsenic, cadmium, chromium and nickel in cancerous and healthy tissues from patients with head and neck cancer.
Chronic exposure to heavy metals has long been recognized as being capable to increase head and neck cancer incidence among exposed human populations. Head and neck cancer is a significant public health issue in Tunisia. The aim of the present study was to evaluate the concentrations of As, Cd, Cr and Ni in healthy and tumor tissues of head and neck cancer patients. Metal concentrations were determined in tumor and healthy tissues of 101 head and neck cancer patients, using Atomic Absorption Spectrometry. The As, Cd, Cr, and Ni levels in tumor tissues were 3.4, 2.5, 1.3 and 1.5 times higher than those of healthy tissues (p<0.05), respectively. Tumor tissue metal levels were higher in men than in women. As and Cd levels in tumor and healthy tissue samples of patients smokers are significantly higher than those of non-smokers (p<0.05). A strong effect of cumulative smoking as expressed in the number of pack per year, and tumor tissue Cd levels were positively associated with three groups of age (<40, 51-60 and >60 years) in both never-smokers and ever-smokers (<20 and ≥20 pack per year). Healthy tissue Cd levels were negatively associated with age in those three groups of smokers. The highest Cd and Cr concentrations among both workers and non-workers were observed in tumor tissues. The Cd and Cr in tissues of farmers, bricklayers and painters were all significantly higher among the workers as compared with the non-workers group. Tissue metal levels have increased due to smoking and occupational exposure. Heavy metal exposure via tobacco smoking and occupational exposures may increase the risk of head and neck in the Tunisian population.


Sources of Metacognitive Inefficiency.
Confidence judgments are typically less informative about one's accuracy than they could be; a phenomenon we call metacognitive inefficiency. We review the existence of different sources of metacognitive inefficiency and classify them into four categories based on whether the corruption is due to: (i) systematic or nonsystematic influences, and (ii) the input to or the computation of the metacognitive system. Critically, the existence of different sources of metacognitive inefficiency provides an alternative explanation for behavioral findings typically interpreted as evidence for domain-specific (and against domain-general) metacognitive systems. We argue that, contrary to the dominant assumption in the field, metacognitive failures are not monolithic and suggest that understanding the sources of metacognitive inefficiency should be a primary goal of the science of metacognition.


Lactobacillus rhamnosus bacteremia: an emerging clinical entity.
Lactobacillus spp. are ubiquitous commensals of the normal human flora that are only occasionally found in clinical infections. Their role in human disease is established for infectious endocarditis but is controversial for other infections. We sought to characterize clinically associated Lactobacillus spp. We conducted a retrospective study, which consisted of the screening of Lactobacillus isolates obtained in our laboratory from January 2004 to December 2009. The polymerase chain reaction (PCR) assay was selected as the gold standard method. The isolates were first identified using API Coryne strips, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and 16S rRNA gene sequencing. Lactobacillus tuf gene-based identification was used when the 16S rRNA results were inconclusive. Among the 60 strains of Lactobacillus spp. obtained in our laboratory, L. rhamnosus was the most commonly isolated species and was found in blood cultures from 16 patients. Combined with 45 patients reported in the literature, we found that patients presenting with L. rhamnosus bacteremia experienced nosocomial infections associated with both immunosuppression (66 %) and catheters (83 %).


Dobutamine stress echocardiography for assessment of myocardial viability and ischemia in acute myocardial infarction treated with thrombolysis.
To evaluate the role of dobutamine echocardiography for early assessment of myocardial viability and ischemia in acute myocardial infarction (MI), 59 patients with thrombolyzed acute MI underwent low- (5-10 micrograms/kg/min, 8 patients) and high-dose (20-40 micrograms/kg/min, 51 patients) dobutamine echocardiography at a mean of 8 +/- 4 days after acute MI. Myocardial viability in the infarct zone was documented in 43 of 59 (73%) patients (group 1), in whom mean asynergy score index decreased from 1.6 +/- 0.3 at baseline to 1.3 +/- 0.2 (p < 0.001), after low-dose dobutamine. No viability was present in 16 of 59 (27%) patients (group 2). At follow-up, recovery of regional contractile function was observed in group 1 (asynergy score index decreased from 1.6 +/- 0.3 to 1.4 +/- 0.3; p < 0.001), but not in group 2 patients. Sensitivity, specificity, and negative and positive predictive values of low-dose dobutamine echocardiography in predicting spontaneous recovery of function were 79%, 68%, 50%, and 89%, respectively. Of the 51 patients who underwent high-dose dobutamine, 26 of 36 (72%) group 1 patients showed a deterioration of contractility in the infarct zone indicative of myocardial ischemia compared with only 1 of 15 (7%) group 2 patients. At follow-up, recovery of regional function was greater in patients with no evidence of myocardial ischemia at high doses than in those with an ischemic response.(ABSTRACT TRUNCATED AT 250 WORDS)


Combination endoscopic surgical debridement and transcutaneous retrobulbar amphotericin B for acute rhino-orbital-cerebral aspergillosis.
To report a case of acute rhino-orbital-cerebral aspergillosis with aggressive intracranial and orbital extension co-managed medically and surgically with endoscopic sinus debridement and multiple retrobulbar injections of amphotericin B. A 70-year-old male patient presented via external transfer with headaches and left ophthalmoplegia concerning for severe complicated sinusitis with intracranial and left orbital spread. His history is notable for a simultaneous heart-kidney transplant three years prior on chronic immunosuppression. Ophthalmologic examination revealed complete ophthalmoplegia in the left eye with no light perception concerning for a left orbital apex syndrome. The patient was taken to the operating room twice for endoscopic sinus debridement and three separate retrobulbar injections of amphotericin B. Fungal cultures from surgical specimens grew isolated Aspergillus fumigatus. Patient's symptoms gradually improved and repeat MRI demonstrated resolution of pansinusitis, sparing left eye exenteration. Multidisciplinary management of invasive fungal rhinosinusitis in the setting of profound immunosuppression poses a significant challenge. While surgical debridement remains the cornerstone approach, the achievable reduction in disease burden may be augmented by targeted retrobulbar antimicrobials.


Human polyomaviruses identification by logic mining techniques.
Differences in genomic sequences are crucial for the classification of viruses into different species. In this work, viral DNA sequences belonging to the human polyomaviruses BKPyV, JCPyV, KIPyV, WUPyV, and MCPyV are analyzed using a logic data mining method in order to identify the nucleotides which are able to distinguish the five different human polyomaviruses. The approach presented in this work is successful as it discovers several logic rules that effectively characterize the different five studied polyomaviruses. The individuated logic rules are able to separate precisely one viral type from the other and to assign an unknown DNA sequence to one of the five analyzed polyomaviruses. The data mining analysis is performed by considering the complete sequences of the viruses and the sequences of the different gene regions separately, obtaining in both cases extremely high correct recognition rates.


Intraoperative cryoanalgesia for postthoracotomy pain relief.
In a randomized study, 63 patients were investigated for the benefits of cryoanalgesia after thoracotomy. Analgesia and its dependent effects such as enhancement of mobility, respiratory function, and reduced need of narcotics were evaluated. No significant differences in these variables were observed between the cryoanalgesia group and the control group. However, moderate to severe neuralgia was found in a number of patients in the cryoanalgesia group in the late postoperative period. Cryoanalgesia for pain relief after thoracotomy is not recommended.


Leigh's disease in an adult with evidence of "inhibitor factor" in family members.
A 21-year-old man with a longstanding history of impaired visual acuity, strabismus, broad-based gait, and below-average intellectual capacity developed respiratory difficulties and intermittent generalized weakness at age 19. He subsequently showed signs of massive brainstem dysfunction and died. Postmortem examination demonstrated changes compatible with subacute necrotizing encephalomyelopathy of Leigh involving portions of the diencephalon, midbrain, pons, and medulla as well as portions of the spinal cord and optic nerves. Evaluation of family members for presence of the urinary inhibitor factor for thiamine diphosphate phosphoryl transferase revealed abnormal levels in a brother, a maternal uncle, and the maternal grandfather of the patient.


Expression of GCDFP-15 and AR decreases in larger or node-positive apocrine carcinomas of the breast.
Apocrine carcinoma of the breast is typically, though not always, positive for gross cystic disease fluid protein-15 (GCDFP-15). In order to clarify the clinical significance of GCDFP-15 in apocrine carcinomas, GCDFP-15 expression was examined in apocrine carcinomas of different stages and compared with clinicopathological factors. Apocrine lesions reportedly exhibit an unusual immunohistochemical status, expressing androgen receptors (AR) instead of oestrogen receptors (ER), progesterone receptors (PR), or bcl-2. Their expression was also examined. Fifty-two apocrine carcinomas were examined immunohistochemically. Thirty-nine (75%) and 29 (56%) were positive for GCDFP-15 and AR, respectively. GCDFP-15 positivity was significantly lower in infiltrating carcinomas than intraductal carcinomas (P = 0.0111). In infiltrating carcinomas, GCDFP-15 positivity was significantly low in tumours > or = 15 mm (P = 0.0005) and node-positive tumours (P = 0.0004). Similar phenomena were observed for AR. Rare cases were positive for ER (3.8%), PR (5.8%), and bcl-2 (1.9%). GCDFP-15 positivity is transient and should not be considered a definitive marker of apocrine carcinomas. Cases which have apocrine features but lack GCDFP-15 expression should rather be considered as advanced apocrine carcinomas. ER/PR/bcl-2 negativity will sometimes be helpful to confirm the diagnosis of apocrine carcinoma, because it is more consistent than GCDFP-15/AR positivity.


Influence of radiation treatment technique (IMRT vs. 3D-RT) on acute toxicity and prognostic factors for survival for anal cancer.
We compared our institutional experience with intensity-modulated radiotherapy (IMRT) and 3D-conformal radiotherapy (3D-RT) for definitive treatment of primary anal cancer. We performed a single-institution retrospective review of all patients with anal squamous cell carcinoma treated with definitive (chemo) radiotherapy with curative intent from 2004 through 2018. We assessed several prognostic factors in respect to relevant survival endpoints. In addition, acute toxicities were determined and compared between IMRT and 3D-RT patients. This study included 94 patients (58 IMRT, 36 3D-RT). Mean follow up for all patients, for IMRT and 3D-RT patients was 61 months (range 6-176), 46 months (range 6-118), and 85 months (range 6-176), respectively. 5-year overall survival (OS) was 86%, disease-free survival (DFS) was 72%, and colostomy-free survival (CFS) was 75% in the IMRT cohort. In the 3D-RT cohort, OS was 87%, DFS was 71%, and CFS was 81% (all p > 0.05). Male gender and Karnofsky Index (KI) were revealed as independent prognostic factors for 5-year OS (p = 0.017; p = 0.023). UICC stage was an independent prognostic factor for DFS and CFS (p = 0.023; p = 0.042). In addition, the pre-treatment leukocyte count was an independent prognostic factor for CFS (p = 0.042). Acute grade ≥ 3 toxicity was not significantly different between IMRT and 3D-RT patients, but the IMRT cohort had favorable outcomes. This study confirmed IMRT as the primary definitive treatment of anal cancer. With similar survival rates, IMRT had the potential to reduce acute toxicity by sparing organs at risk. Promising prognostic factors such as BMI, KI, and leucocyte and hemoglobin levels should be further investigated.


A photoacoustic calorimetry study of horse carboxymyoglobin on the 10-nanosecond time scale.
The development of a photoacoustic calorimeter with a time resolution of 10 ns is presented, and the dynamics of the enthalpy and volume changes found in the photodissociation of CO from horse carboxymyoglobin are examined. With this enhanced time resolution a new transient species, the lifetime of which is 29 ns at 20 degrees C, is observed in the ligand dissociation process.


Diagnosis and treatment of pericallosal artery aneurysms.
Pericallosal artery aneurysms are not common clinically. The microsurgery and endovascular therapy are surgically challenging operations. The objective of the study is to summarize their clinical symptoms and optimal treatment strategies of pericallosal artery aneurysms. Nine cases of pericallosal artery aneurysms detected by digital subtraction angiography (DSA) were reviewed. The clinical manifestation, brain imaging characteristics, and optimal treatment methods were summarized. Patients with spontaneous aneurysm had good clinical outcomes after endovascular coiling or microsurgical clipping treatment. There were no any neurological function deficits in five patients. One patient suffered from permanent neurological function deficits. Patients with traumatic aneurysm pericallosal had relatively poor outcomes, including two patients showing disturbed consciousness and the paralysis of the lower limbs with slow recovery, and one patient was dead after the surgery. Spontaneous subarachnoid hemorrhage and interhemispheric fissure hematoma suggest spontaneously pericallosal aneurysm, while traumatic corpus callosum hematoma as well the accompanying embryo of intraventricular hemorrhage suggest traumatic pericallosal aneurysm. Endovascular embolization is the primary surgical treatment for pericallosal aneurysm, while patients with pericallosal aneurysm are not suitable for surgical treatment. Microsurgical clipping treatment may be a choice. However, both of these treatment strategies have high risk.


Apoptotic signaling by c-MYC.
c-MYC has a pivotal function in growth control, differentiation and apoptosis, and its abnormal expression is associated with many tumors. Overexpression of c-MYC sensitizes cells to apoptosis by a variety of stimuli. The decision of a cell to undergo apoptosis and how this apoptotic response is regulated by c-MYC depends on the specific cell type and the physiological status of the cell. Multiple cooperating molecular pathways of cell survival and apoptosis determine whether a cell lives or dies, and understanding how c-MYC interfaces with these pathways to influence the survival of cells is important to understand normal and abnormal development, tumor initiation and progression, and response of tumors to different treatment regimens. This article will provide an overview of the function of the tumor suppressor gene product p53 in the c-MYC-mediated apoptotic response and how c-MYC amplifies the intrinsic mitochondrial pathway and triggers and/or amplifies the death receptor pathways. Finally, a model for how deregulated c-MYC prematurely triggers the normal apoptotic response associated with terminal myeloid differentiation while also blocking the differentiation program is presented.


Clinical features and prognoses of 23 patients with chronic granulomatous disease followed for 21 years by a single hospital in Japan.
In this paper, we examined the details of severe infections, treatment efficacies, and the prognoses of 23 Japanese patients with chronic granulomatous disease (CGD). We described the mean ages at diagnosis and follow-up, which were 2.8 years (range, 0.7-10 years) and 14.9 years (range, 0.2-28.4 years), respectively. There were three deaths, two from Aspergillus pneumonia and one from liver abscess. Eighteen of the 23 patients (78%) had a complete loss of gp91phox, and three had p22-phox and one had p67phox deficiencies. Aspergillus species were found in 45% of 174 severe infections. The mean height and weight of the 20 surviving patients were -0.8 +/- 1.3SD and -1.9 +/- 1.9SD below the means for age, respectively. Short stature and underweight (below the 10th percentile of the means) for age were seen in 22% and 17% of the patients, respectively. This growth retardation reflects the severity of the disease. At 20 years of age, there was 87% survival. Ongoing prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) or antifungal drugs was given in 16 and 11 patients, respectively. Interferon-gamma (IFN-gamma) was given once a week to 14 patients. Four patients underwent hematopoietic stem cell transplantation (HSCT) and are currently well. There were infections observed in three of 21 identified related carriers of X-linked CGD. A carrier with a liver abscess had 5% normal neutrophils during the acute phase of infection, which returned to 40% normal neutrophils after recovery. The high survival rate in this hospital results from regular follow-up and prophylaxis with TMP-SMX and anti-fungal drugs beginning at the time of diagnosis, along with treatment with weekly IFN-gamma.


Detecting equilibrium cytochrome c folding intermediates by electrospray ionisation mass spectrometry: two partially folded forms populate the molten-globule state.
Nanoelectrospray ionization mass spectrometry (nano-ESI-MS) is applied to the characterization of ferric cytochromec (cytc) conformational states under different solvent conditions. The methanol-induced molten-globule state in the pH range 2.6-3.0 is found to be populated by two distinct, partially folded conformers I(A) and I(B). The more compact intermediate I(B) resembles that induced by glycerol in acid-unfolded cytc. The less compact one, I(A), also can be induced by destabilization of the native structure by trifluoroethanol. I(A) and I(B) can be detected, in the absence of additives, around the midpoint of the acid-induced unfolding transition, providing direct evidence for involvement of equilibrium folding intermediates in cytc conformational transitions at low pH. This study shows that mass spectrometry can contribute to the characterization of molten-globule states of proteins by detection of distinct, although poorly populated, conformations involved in a dynamic equilibrium.


Preservation of human placenta facilitates multicenter studies on the local immune response in normal and aberrant pregnancies.
Our standard procedure for phenotypic and functional analysis of immune cells present in the placenta is to isolate leukocytes from the decidua within five hours of the delivery. However, this results in logistical problems with deliveries at night, weekends or in other medical centers. Collecting placentas after complicated pregnancies is even more difficult owing to the low prevalence and the often unscheduled delivery. The aim was to investigate the possibility of preserving the human placenta before phenotypic and functional analysis of decidual lymphocytes. Placentas were obtained after uncomplicated pregnancy. The tissue was divided into two equal parts: decidual lymphocytes from one part were isolated within five hours according to our standard procedure, whereas the other part was preserved in either Celsior(®), a storage solution for solid organ preservation, or phosphate-buffered saline (PBS) for 24h at 4°C before isolation. Overall, the phenotype and functional capacity of decidual lymphocytes isolated within five hours was comparable to decidual lymphocytes isolated after 24-h preservation in Celsior(®) or PBS. Minor differences were found between decidual lymphocytes isolated within five hours and decidual lymphocytes isolated after 24-h preservation in Celsior(®). The results indicate that PBS is sufficient to preserve the placenta for 24h for phenotypical and functional studies. The ability to preserve the placenta will simplify the procedure for the isolation of decidual lymphocytes and makes it easier to analyze tissue from women who deliver during the night, at weekends or in other hospitals, and possibly even women with complicated pregnancies.


Evaluation of urinary metal concentrations and sperm DNA damage in infertile men from an infertility clinic.
This study aimed to examine associations between urinary metal concentrations and sperm DNA damage. Thirteen metals [arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), molybdenum (Mo), mercury (Hg), nickel (Ni), selenium (Se), and zinc (Zn)] were detected in urine samples of 207 infertile men from an infertility clinic using inductively coupled plasma mass spectrometry, and also, sperm DNA damage (tail length, percent DNA tail, and tail distributed moment) were assessed using neutral comet assay. We found that urinary Hg and Ni were associated with increasing trends for tail length (both p for trend<0.05), and that urinary Mn was associated with increasing trend for tail distributed moment (p for trend=0.02). These associations did persist even when considering multiple metals. Our results suggest that environmental exposure to Hg, Mn, and Ni may be associated with increased sperm DNA damage.


Transient osteoporosis of the hip (TOH) is a rare condition with acute onset of hip pain. TOH is self-limiting and often leads to complete remission of symptoms within 6-12 months. This case report presents a 44-year-old male diagnosed with TOH. As part of the treatment plan, the patient received intravenous bisphosphonate with 5 mg zoledronic acid. A few weeks after administration, the patient reported almost full symptomatic remission.


Endothelial lipase: its role in cardiovascular disease.
Endothelial lipase (EL) has recently been identified as a new member of the triglyceride lipase gene family. EL shares a relatively high degree of homology with lipoprotein lipase and hepatic lipase, but it appears to be more specific at hydrolyzing phospholipids than lipoprotein lipase and hepatic lipase. EL is also the only identified lipase that is synthesized and expressed by endothelial cells. Data from in vitro and in vivo animal studies have suggested that EL may play a key role in modulating the metabolism of high density lipoproteins. Data are less consistent in clarifying how EL contributes to the metabolism of apolipoprotein B-containing lipoproteins. Investigations in humans are scarce. To date, increased plasma EL concentrations have been associated with a deteriorated lipoprotein-lipid profile along with elevated plasma triglyceride and apolipoprotein B concentrations, as well as with smaller low density lipoprotein particle size. Elevated proinflammatory cytokine concentrations and an increased prevalence of the metabolic syndrome have also been observed among individuals with elevated plasma EL concentrations. Taken together, data suggest that EL is one of several key regulatory enzymes of lipoprotein-lipid metabolism and that a proinflammatory state, such as the metabolic syndrome, may be implicated in the processes relating plasma EL concentrations and lipoprotein concentrations. EL should thus be considered to play an important role in the pathophysiology of cardiovascular disease.


The impact of changing people with sleep apnea using CPAP less than 4 h per night to a Bi-level device.
Pressure intolerance is a reason for poor acceptance and subsequent compliance in some patients starting treatment with continuous positive airway pressure (CPAP). In unselected populations initiating CPAP; different types of pressure generating device have not been found to improve compliance. We hypothesized that using Bi-level PAP for patients who reported pressure related discomfort as a cause for poor compliance with CPAP might increase their hours of treatment use. Patients using CPAP <4 h/night with symptoms to suggest pressure intolerance were randomized to receive either a Bi-level PAP device or a new CPAP for 4 weeks. Following a washout period of 2 weeks, they were crossed over to the other device for 4 weeks. Twenty eight volunteers completed the protocol. Compared to the baseline (mean 1.49 h per night), improvement in compliance was noticed when changed to a new CPAP (2.23 h, p = 0.006) or Bi-level PAP (2.73 h, p < 0.001). The trend suggesting superior compliance with a Bi-level PAP device compared to new CPAP was not significant (p = 0.059) and there were no differences in subjective or objective measures of sleepiness. The results of this study suggest that routine intervention with Bi-level PAP in this group of sub-optimally compliant individuals was not very effective in improving PAP usage. There is however a subgroup of patients who complains of difficulty with exhalation; where favorable trends towards improved compliance were observed on Bi-level PAP.


A comparative study assessing the effect of haematological and biochemical parameters on the pathogenesis of malaria.
Malaria is one of the most common parasitic disease affecting mankind since millennia. The most pronounced changes related to malaria involve the blood and the blood forming system, the spleen and the liver. The abnormal haematological and biochemical parameters observed in malaria cases adversely affect the prognosis of the disease. The aim of this study was to assess the severity of malaria by observing the significant abnormalities in haematological and biochemical parameters in the malaria infected cases as compared to the healthy controls. The study population comprised of 138 individuals, of which 69 were malaria cases and 69 were apparently healthy controls. All the 138 individuals were subjected to haematological and biochemical workup, following which statistical analysis was done to observe any association of altered haematological and biochemical parameters with severity of malaria, as compared to the healthy controls. Among the 138 study population, 69 patients were malaria cases whereas the other 69 were healthy controls. Haematological investigations revealed, that the haemoglobin levels, total RBC counts and haematocrit were significantly altered in the malaria cases as compared to the healthy controls. Also the leucogram profile showed significant leucopenia and neutropenia in the malaria patients as compared to the controls. Thrombocytopenia was also seen to be more pronounced in the malaria infected. The liver enzymes and serum bilirubin levels were raised in the malaria cases more than the controls. Altered haematological and biochemical parameters are indicators of disease progression to severity. Early detection and management of these parameters, will prevent the development of complications in malaria.


Acrophialophora fusispora brain abscess in a patient with acquired immunodeficiency syndrome: a case report and review of the literature.
We reported a fatal case of brain abscess caused by Acrophialophora fusispora in a patient with acquired immunodeficiency syndrome. Identification of the fungus was based on microscopic morphology and sequence analyses of the internal transcribed spacer 1 (ITS1) and 2 (ITS2) of ribosomal RNA gene from the isolate recovered from brain abscess. Four published cases were reviewed as well.


A novel and fast-responsive two-photon fluorescent probe with modified group for monitoring endogenous HClO accompanied by a large turn-on signal and its application in zebrafish imaging.
Hypochlorous acid (HClO) plays a critical role in physiological activities of maintaining the stable oxidation balance of organisms, which was proved to relate to some serious diseases. In this work, 4-nitrobenzenesulfonylhydrazide based fast-responsive two-photon fluorescent probe CoPh-ClO was designed and synthesized reasonably, which possessed low cytotoxicity, good anti-interference characteristics, a large Stokes shift (85 nm), and good two-photon performance. In addition, probe CoPh-ClO was successfully applied to detect exogenous HClO in living HeLa cells and endogenous HClO in living RAW264.7 cells respectively. Moreover, we successfully achieved tissues imaging with a deep penetration depth of 65 µm and zebrafish imaging accompanied with a high contrast (about 45-fold). Interestingly, the introduce of benzene ring between fluorophore and reaction site made probe CoPh-ClO more sensitive (only 20 s) with a large turn-on signal. The probe CoPh-ClO was modified and possessed better stability (more than 10 mins) even in excessive HClO. All of mentioned above merits demonstrated that CoPh-ClO could be a promising imaging tool for monitoring HClO in various physiological processes, and the introduction of benzene ring would provide a new perspective for the development of multi-function probes.


Clinical application of adenosine and ATP for pain control.
This review summarizes clinical application of adenosine and adenosine 5'-triphosphate (ATP) in pain conditions. Investigations have been performed in patients with acute perioperative pain or chronic neuropathic pain treated with intravenous adenosine or ATP, or intrathecal adenosine. Characteristic central adenosine A1 receptor-mediated pain-relieving effects have been observed after intravenous adenosine infusion in human inflammation/sensitization pain models and in patients with chronic neuropathic pain. Adenosine compounds, in low doses, can reduce allodynia/hyperalgesia more consistently than spontaneous pain, suggesting that these compounds affect neuronal pathophysiological mechanisms involved in central sensitization. Such pain-relieving effects, which are mostly mediated via central adenosine A1 receptor activation, have a slow onset and long duration of action, lasting usually for hours or days and occasionally for months. With acute perioperative pain, treatment with a low-dose infusion of adenosine compounds and the A1 receptor-mediated central antisensitization mechanisms may play only a minor part in the total perioperative pain experience. By administering sufficient doses of adenosine compounds during surgery, however, significant and long-lasting perioperative pain relief can be achieved via central A1 receptor-mediated antinociceptive/analgesic actions as well as via peripheral A2a or A3 receptor-mediated antiinflammatory actions. Thus, adenosine compounds have significant potential for alleviating various types of pain.


Prejunctional modulation of acetylcholine release from the skeletal neuromuscular junction: link between positive (nicotinic)- and negative (muscarinic)-feedback modulation.
1. Presynaptic receptor-mediated modulation of stimulation-evoked [3H]-acetylcholine[( 3H]-ACh) release from the neuromuscular junction was studied in the region of the mouse hemidiaphragm which contains the motor endplates, and which can easily be loaded with [3H]-choline. This method made it possible to detect exclusively the [Ca2+]0-dependent, quantal release of [3H]-ACh in response to axonal stimulation. 2. Atropine enhanced, and non-depolarizing muscle relaxants [+)-tubocurarine, pancuronium and pipecuronium) reduced, the release of [3H]-ACh evoked by high frequency trains of stimulation (50 Hz, 40 shocks) of the phrenic nerve. The effect of (+)-tubocurarine was frequency-dependent as at 5 Hz (40 shocks) it was less effective than at 50 Hz. The resting release of [3H]-ACh was not affected by these compounds. These findings indicate that ACh released into the synaptic gap by axonal firing reaches a concentration sufficient to influence its own release by a prejunctional effect. 3. The anticholinesterase, physostigmine sulphate, enhanced the release of [3H]-ACh in a concentration-dependent manner. This effect was mediated via prejunctional nicotinic receptor stimulation: (+)-tubocurarine, pancuronium and pipecuronium completely prevented the effect of physostigmine. 4. When the prejunctional nicotinic and muscarinic receptors were stimulated by a high concentration of extracellular ACh which had accumulated in the junctional gap in the presence of physostigmine, atropine did not influence the evoked release of [3H]-ACh. However, when the effect of endogenous ACh on nicotinic receptors was prevented by (+)-tubocurarine, atropine enhanced the release. 5. It is concluded that quantally-released ACh from motor endplates is subject to prejunctional automodulation: (a) ACh facilitates its own release via an effect on prejunctional nicotinic receptors (positive feedback), (b) ACh release is reduced by an action on muscarinic receptors. When the nicotinic receptor-mediated facilitation is fully operative, the muscarinic receptor-mediated negative feedback is much less effective. It is supposed that there is a link between the two feedback mechanisms possibly at the level of the second messenger system(s).


Paclitaxel reduces anti-dsDNA antibody titer and BUN, prolonging survival in murine lupus.
We evaluated the effect of paclitaxel on the severity of autoimmunity in the murine model of systemic lupus erythematosus (SLE), NZB x NZW F1 mice. Fifteen 20 week old (NZB x NZW) F1 female mice were given a dose of 10 mg/kg paclitaxel by the intraperitoneal route on three alternate days followed by 7.5 mg/kg on three additional alternate days. This pattern of treatment was repeated every 4 weeks for a period of 28 weeks. 20 control mice were injected intraperitoneally with an equal volume of the vehicle used. Serum anti-double stranded DNA (dsDNA) antibody titers and the blood urea nitrogen (BUN) were significantly diminished in the paclitaxel treated group compared to the vehicle treated group. While the onset of proteinuria appeared to be delayed in the experimental group, the difference was not significant. Survival rate improved significantly in paclitaxel treated group (p = 0.04 by log-rank test). These results suggest that paclitaxel is beneficial in the suppression of autoimmunity in this strain of mice by reducing the anti-dsDNA antibody titer and the BUN, prolonging survival.


Verapamil and flunarizine protect the isolated perfused rat liver against warm ischemia and reperfusion injury.
Using the model of the isolated perfused rat liver, we investigated the influence of the two pharmacologically different calcium channel blockers, verapamil and flunarizine, on changes of ion homeostasis, liver weights, pH deviations and enzyme activities during warm ischemia (37 degrees C) and reperfusion. The LDH and GLDH activities were determined and the calcium, potassium, and sodium concentrations were measured in the effluent. Warm ischemia (180 min) caused an increased enzyme release, a high influx of calcium and sodium into the liver and a massive potassium efflux current. Normoxic reperfusion led to a further increase in hepatic enzyme release and although the loss of potassium ceased, the calcium influx into the liver continued. By the end of reperfusion the liver weight had increased significantly (P < 0.01) in the control group. The two calcium entry blockers were added to the perfusate in various concentrations. Both substances protected the liver against warm ischemia and normoxic reperfusion damage, but they did not inhibit calcium inflow. However, the potassium efflux was significantly reduced by all concentration tasted (P < 0.001). After reperfusion the liver weights were significantly lower in the treated groups (P < 0.001) than in control animals. Thus, the calcium entry blockers verapamil and flunarizine protect liver cells against damage caused by warm ischemia and reperfusion. Furthermore, they prevent the disruption of intracellular potassium homeostasis, which seems to be related to improved volume regulation of liver cells.


Frequency and pattern of Chinese herbal medicine prescriptions for chronic hepatitis in Taiwan.
Chinese herbal medicine (CHM) has been commonly used in treating liver diseases in Asian countries. To conduct a large-scale pharmacoepidemiological study and evaluate the frequency and pattern of CHM prescriptions in treating chronic hepatitis. We obtained the database of traditional Chinese medicine outpatient claims from the national health insurance in Taiwan for the whole 2002. Patients with chronic hepatitis were identified by the corresponding diagnosis of International Classification of Disease among claimed visiting files. Corresponding prescription files were analyzed, and association rule were applied to evaluate the co-prescription of CHM in treating chronic hepatitis. Among the 91,080 subjects treated by CHM for chronic hepatitis, the peak age was in the 40 s, followed by 30 s and 50 s. Male/female ratio was 2.07:1. Long-dan-xie-gan-tang and Saliva miltiorrhiza (Dan-shen) were the most commonly prescribed Chinese herbal formula and single herbal drug, respectively. The most common two-drug prescription was Jia-wei-xia-yao-san plus Saliva miltiorrhiza, and the most common three-drug prescription was Jia-wei-xia-yao-san plus Saliva miltiorrhiza and Artemisia capillaries (Yin-chen-hao). This study showed the utilization pattern of Chinese herbal drugs or formulae in treating chronic hepatitis. Further researches and clinical trials are needed to evaluate the efficacy of these Chinese herbs or its ingredients in treating chronic hepatitis.


Racial differences in birth weight of term infants in a northern California population.
Census data show that an increasing proportion of the population of the United States is of Asian or Hispanic origin. Reference curves used to characterize fetal growth relative to gestational age are predominantly based on data for White infants. The goal of this study was to compare the birth weight distributions for term Asian or Hispanic infants with that for White infants, and to determine whether the prevalence of small (SGA) or large size(LGA) for gestational age differs between Asian or Hispanic and White infants. A community hospital in Northern California. Data was collected prospectively from May 1 to September 13, 2000 on all singleton term infants born at this hospital. Gestational age was assessed by the best obstetrical estimate and ethnicity was determined by parental report. Infants were categorized as White, Hispanic, Chinese, Asian Indian, Other Asian, and Other. Birth weights, length, and head circumferences were compared using ANOVA and the Student-Newman-Keuls test. Differences in rates of diagnosis of SGA or LGA were assessed by chi square. 1539 infants were included in the study sample; 30% were White, 21% Asian Indian, 15% Chinese, 9% Hispanic, 7% other Asian, and 18% Other. Asian (Chinese, Asian Indian, or Other Asian), Hispanic, and Other babies had lower mean birth weights, shorter mean lengths, and smaller mean head circumferences than White babies. Asian, Hispanic, and Other male babies were lighter, shorter, and had smaller heads than white male babies. Asian females, but not Hispanic or Other ones, were lighter and had smaller head circumferences than White females; Asian Indian, Other Asian, and Other females had shorter lengths than White female infants. Indian and Other Asian, but not Chinese, babies were more likely than White babies to be SGA; babies in all three Asian groups were less likely than White babies to be LGA. Failure to account for ethnic differences in intrauterine growth may lead to inaccurate diagnosis of fetal growth abnormalities in infants of Asian ancestry.


Particulate waste outflow from fish-farming cages. How much is uneaten feed?
Particulate wastes drive benthic organic enrichment from cage fish farming. Differentiation between faeces and uneaten feed estimates at cage level are of great value to both economize the feeding process and reduce waste. This study estimates the particulate waste outflowing cages at different depths and orientations, and the wasted feed component by combining in situ measurements and modelling. Particulate matter flux (PMF) was greater vertically through the cage bottoms (60.89%), but lateral outflow was also substantial (39.11%). PMF occurs all around the cages, and the influence of the mainstream current was low. Wasted feed was greatly variable, reaching high values (about 50% of supplied feed. The self-application of feed wastage monitoring and estimates by fish farmers is recommended to improve sustainability.


Origins and regional distribution of blood flow to the respiratory muscles in conscious sheep.
The blood flow to the portions of the diaphragm (sternal, costal, and crural) and to the external and internal intercostal muscles was measured, using radio-labelled microspheres, in 12 young sheep breathing quietly. We calculated total blood flow and oxygen uptake of the diaphragm (VO2di). We also determined the proportion of diaphragmatic and intercostal muscle blood flow that arose from the descending aorta. Diaphragmatic blood flow (Qdi) was 0.62 +/- 0.04% of cardiac output (mean +/- SEM). VO2di was 1.53 +/- 0.15 ml X min-1 X 100 g-1, and was linearly related to Qdi. When standardized for weight Qdi was 28.3 +/- 1.5 ml X min-1 X 100 g-1, significantly greater than both external intercostal muscle blood flow (18.9 +/- 2.6 ml X min-1 X 100 g-1; P less than 0.05), and internal intercostal muscle blood flow (11.4 +/- 1.4 ml X min-1 X 100 g-1; P less than 0.01). Blood flow to the costal portion of the diaphragm was significantly less than blood flow to the crural portions. There was no difference between flow to these portions and to the sternal portion of the diaphragm. The blood supplying the dorsal-most regions of the diaphragm arose predominantly from the descending aorta. The results suggest that the crural portions work at a higher rate than the costal portions under resting conditions.


Heart failure management with ambulatory pulmonary artery pressure monitoring.
Remote monitoring strategies have been developed to improve ambulatory care of heart failure patients and reduce heart failure hospitalizations. This article evaluates the CardioMEMS device, an implantable wireless pulmonary artery pressure monitor. We provide a historical review of remote monitoring in heart failure along with an in-depth analysis of the rationale, evidence, and limitations of the CardioMEMS device.


Deep eutectic solvent as an efficient modifier of low-cost adsorbent for the removal of pharmaceuticals and dye.
Waste from biomass was used to prepare a low-cost biochar-clay hybrid adsorbent. The hybrid adsorbent was synthesised by combining Kaolin with biomass (Vitex doniana), thereafter, modified with Deep Eutectic Solvent (DES). The materials were characterised using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectrometry (FTIR), Thermal gravimetric analysis (TGA), and Brunauer-Emmett-Teller (BET), also, pHpzc of the materials were studied. The resultant adsorbents were used for both column and batch adsorption of organic pollutants; dye (Acid Blue 74; AB74) and pharmaceuticals (ciprofloxacin; CIP and acetaminophen; ACTE). Column adsorption capacity, effect of pollutant concentration and effect of flow rate were studied, also, the column was modelled using Thomas, Yoon-Nelson and Adams-Bohart model. Furthermore, batch adsorption experiments were performed, effect of change in pH, time, dose and concentration were studied. Batch adsorption data were fitted with isotherm and kinetic models. The experiment showed tremendous increase in adsorption capacity when the hybrid adsorbent (HYD) was modified with DES (HYD-DES). Acid Blue 74 on HYD-DES has the highest column sorption capacity followed by ciprofloxacin and acetaminophen. Adsorption was favoured at pH range of 2-10 for both AB74 and ACTE as there is no significant changes in the % removal performance, while adsorption was best at pH 6 and above for CIP. AB74 and CIP are best described by Langmuir isotherm, whereas ACTE adsorption was best explained by Freundlich isotherm equilibrium. The DES modified HYD has shown it can be effectively utilised as possible adsorbent for adsorbing organic dyes and pharmaceuticals.


Urological complications following chemonucleolysis.
Urinary complications following chemonucleolysis have not been reported in the urological literature. We report a case of urinary retention, perineal hypoesthesia and penile dysesthesia following L5 to S1 chemonucleolysis with chymopapain and review the literature in this area.


A heart in a heart: a case report of spontaneous flail of bicuspid aortic valve.
Aortic regurgitation is attributed to congenital and acquired abnormalities of the aortic valve or aortic valve supporting structures. The most common cause of aortic regurgitation is atherosclerotic degeneration of the valve, especially in the presence of a bicuspid aortic valve. A 25-year-old Persian man with no past medical history, developed dyspnea since 1 week before his first visit to the physician. He was an active person up to this time, and had no history of trauma or chest pain. Transthoracic echocardiography showed severe aortic regurgitation in the context of flail bicuspid aortic valve, with no evidence of endocarditis. Laboratory tests including blood cultures were negative for infection. The patient underwent aortic valve replacement and the diagnosis was confirmed at time of surgery. This case represents noninfective and nontraumatic spontaneous flail of bicuspid aortic valve.


Impact of Dietary Restriction Regimens on Mitochondria, Heart, and Endothelial Function: A Brief Overview.
Caloric restriction (CR) and intermittent fasting (IF) are strategies aimed to promote health beneficial effects by interfering with several mechanisms responsible for cardiovascular diseases. Both dietary approaches decrease body weight, insulin resistance, blood pressure, lipids, and inflammatory status. All these favorable effects are the result of several metabolic adjustments, which have been addressed in this review, i.e., the improvement of mitochondrial biogenesis, the reduction of reactive oxygen species (ROS) production, and the improvement of cardiac and vascular function. CR and IF are able to modulate mitochondrial function via interference with dynamics (i.e., fusion and fission), respiration, and related oxidative stress. In the cardiovascular system, both dietary interventions are able to improve endothelium-dependent relaxation, reduce cardiac hypertrophy, and activate antiapoptotic signaling cascades. Further clinical studies are required to assess the long-term safety in the clinical setting.


Ligand binding free-energy calculations with funnel metadynamics.
The accurate resolution of the binding mechanism of a ligand to its molecular target is fundamental to develop a successful drug design campaign. Free-energy calculations, which provide the energy value of the ligand-protein binding complex, are essential for resolving the binding mode of the ligand. The accuracy of free-energy calculation methods is counteracted by their poor user-friendliness, which hampers their broad application. Here we present the Funnel-Metadynamics Advanced Protocol (FMAP), which is a flexible and user-friendly graphical user interface (GUI)-based protocol to perform funnel metadynamics, a binding free-energy method that employs a funnel-shape restraint potential to reveal the ligand binding mode and accurately calculate the absolute ligand-protein binding free energy. FMAP guides the user through all phases of the free-energy calculation process, from preparation of the input files, to production simulation, to analysis of the results. FMAP delivers the ligand binding mode and the absolute protein-ligand binding free energy as outputs. Alternative binding modes and the role of waters are also elucidated, providing a detailed description of the ligand binding mechanism. The entire protocol on the paradigmatic system benzamidine-trypsin, composed of ~105 k atoms, took ~2.8 d using the Cray XC50 piz Daint cluster at the Swiss National Supercomputing Centre.


A novel oligodendrocyte cell line OLP6 shows the successive stages of oligodendrocyte development: late progenitor, immature and mature stages.
The successive stages of development from oligodendrocyte progenitor to mature oligodendrocyte have been investigated in detail by using stage-specific antibodies. However, no cell lines are available that show stepwise differentiation from oligodendrocyte progenitors to mature oligodendrocytes. Here we show the establishment of an immortalized oligodendrocyte cell line, OLP6, from adult transgenic rats harboring the temperature-sensitive simian virus 40 large T-antigen gene. The OLP6 cells had a fibroblastic morphology and continuously proliferated at 33 degrees C. They displayed growth arrest and multipolar morphology when they were cultured at 39 degrees C. They express the oligodendrocytic markers O4, 2'-3'-cyclic-nucleotide 3'-phosphodiesterase, galactocerebroside and second endothelial differentiation gene receptor-2 at 39 degrees C. The OLP6 cells underwent apoptosis upon serum withdrawal at 39 degrees C. Lysophosphatidic acid inhibited this apoptosis and promoted the expression of myelin basic protein. These results demonstrate that the activation of endothelial differentiation gene receptor-2 exerts anti-apoptosis and myelinogenesis effects on the OLP6 cells. Taken together, the OLP6 cells in the late oligodendrocyte progenitor stage can progress to the immature oligodendrocyte stage by shifting culture temperature. Furthermore, lysophosphatidic acid promoted the maturation of OLP6 cells in the immature oligodendrocyte stage. Such OLP6 cells should provide a potent model system for studying the precise mechanism involved in stepwise differentiation of oligodendrocytes.


Effects of heat stress exposure on porcine muscle satellite cells.
Heat stress (HS) affects cell culture as well as animal production. Although there have been many reports on the disparate effects of heat stress, its effects on mammalian muscle stem cells are still unclear. In this study, we isolated porcine muscle satellite cells (PMSCs) from the femurs of 1-day-old piglets, and cultured them under three temperature conditions: 37 °C, 39 °C, and 41 °C. Exposure to HS not only decreased the viability and proliferation rates of PMSCs, but also regulated the cell cycle and induced apoptosis. High-temperature culture conditions decreased both protein and gene expression of Pax7, a proliferation and maintenance marker of muscle satellite cells, whereas it increased both protein and gene expression of MyoG, a differentiation marker, and promoted myotube formation in the early stage of differentiation induction. In addition, the protein and gene expression of several heat shock proteins (HSPs) in PMSCs increased due to heat treatment. In conclusion, HS induced the cell cycle arrest of PMSCs, thereby reducing the proliferation rate. In addition, high-temperature culture conditions promoted the formation of myotubes at the early stage of differentiation of PMSCs without additives.


The ultrastructural cytochemistry of lactic dehydrogenase, succinic dehydrogenase, dihydro-nicotinamide adenine dinucleotide diaphorase and cytochrome oxidase activities in hair cell mitochondria of the guinea pig cochlea.
The use of cinnamyl nitroblue tetrazolium chloride (DS-NBT) in dehydrogenase experiments (lactic dehydrogenase, succinic dehydrogenase, nicotinamide adenine dinucleotide diaphorase) and 3,3'-diaminobenzidine tetrahydrochloride (DAB) in cytochrome oxidase experiments indicated that mitochondrial oxidoreduction reactions from nicotinamide adenine dinucleotide to cytochrome oxidase are located on the inner mitochondrial membrane in the outer compartment and the intracristate spaces. These reactions behave according to the chemiosmotic hypothesis. The cochlear hair cell mitochondria are cytochemically indistinguishable from free liver mitochondria. The heterogeneous mitochondrial staining pattern is related to the osmolarity of the incubation media, solubility of the enzymes and pH of the medium, but not to the fixation method.


Adherence to Recommended Preventive Behaviors During the COVID-19 Pandemic: The Role of Empathy and Perceived Health Threat.
Coping via empathic responding may play a role in preventive behavior engagement during the COVID-19 pandemic, and unlike trait empathy, is a potentially alterable target for changing health behavior. Our goal was to examine the role of empathic responding in preventive behavior engagement during the COVID-19 pandemic, independent of trait empathy and perceived threat of COVID-19. Participants (N = 2,841) completed a baseline survey early in the pandemic, and a follow-up survey approximately 2 weeks later (M = 13.50 days, SD = 5.61). Preventive health behaviors, including physical distancing and hygiene practices, were assessed at both timepoints. Hierarchical linear regression examined the contributions of trait empathy, perceived threat of COVID-19, and empathic responding at baseline to preventive behaviors at follow-up. Controlling for baseline levels of preventive behaviors and demographic covariates, trait empathy and threat of COVID-19 at baseline were each independently associated with preventive behaviors at follow-up. An interaction between perceived threat and empathic responding indicated that those perceiving high threat of COVID-19 at baseline tended to report engaging in preventive behaviors at follow-up regardless of their levels of empathic responding, whereas for those reporting low levels of perceived threat, higher levels of empathic responding were associated with higher engagement in preventive behavior. When perceived threat of COVID-19 was low, higher empathic responding was associated with increased engagement in preventive behaviors regardless of trait empathy, suggesting that empathic responding can serve as an actionable target for intervention to promote preventive behavior during the pandemic.


[Epidemiology of thalassemia in Sicily. Sicilian Regional Epidemiologic Surveillance. Sicilian Cooperative Group for the Study of Thalassemia and Hemoglobinopathies].
A Sicilian Register of Thalassaemia set up in 1984 revealed 912 cases of Thalassaemia Major and 216 of Th. Intermedia on the island in that year. A significant decrease in the number of Cooley disease births was also noted in 1982-1984.


Factor V Leiden: is it the chief contributor to activated protein C resistance in Asian-Indian patients with deep vein thrombosis?
Deep vein thrombosis is a condition, which has several acquired as well as genetic causes. One of the most common reasons for deep vein thrombosis is activated protein C resistance caused by Factor V Leiden. We examined the risk posed by Factor V Leiden, Hong Kong/Cambridge and HR2 Haplotype mutations in 155 deep vein thrombosis patients and 120 healthy controls in the background of activated protein C resistance. Thirty-one of our patients showed activated protein C resistance of which only 16 carried Factor V Leiden mutation which was a far lower number than what is usually seen in Caucasian population. Factor V Leiden mutation was significantly associated with the risk of deep vein thrombosis (Yates corrected p-value=0.002; 95%CI; odds ratio: 13.7). Factor V Hong Kong/Cambridge and HR2 Haplotype were not found to be associated with the risk of deep vein thrombosis. There is a possibility that Factor V HR2 Haplotype might also be associated with activated protein C resistance even in the absence of Factor V Leiden. Factor V Leiden mutation was seen to contribute far less towards activated protein C resistance in Asian-Indian deep vein thrombosis patients than what has been commonly observed in Caucasians.


Hydroxyethyl starch is an alternative washing solution for peripheral bloodstem cells products.
Cryopreservation of hematopoietic stem cells (HSC) involves slow rate cooling in the presence of a cryoprotectant (DMSO) to avoid the damaging effects of intracellular ice formation. The infusion of DMSO with the thawed product has been related to adverse events. Reduction of DMSO content by washing the HSCs after thawing has been suggested as a method to avoid infusion-related side-effects. Albumin-dextran washing methods have proved useful in thawing HSC products. Dextran40 shortages prompted us to search for suitable alternatives. We report the results of a comparative study of the use of hydroxyethyl starch (HES) as an alternative to dextran40 for washing thawed HSCs products. A total of 10 HSC bags cryopreserved with 10 % DMSO were used. We conducted a paired study; one of the bags was thawed and washed with our standard washing solution (Dextran 40) and the paired bag with HES solution with a final HES and Human Serum Albumin (HSA) concentration of 2.4 % and 4.2 % respectively. Each final product was tested immediately after washing (sample 0') and after 90 min (sample 90') for total nucleated cells (TNC) recovery, acridine orange viability, viable CD34+ enumeration, and clonogenicity. No significant difference was found for any of the cell counts, viability tests, cell recovery, or potency. We can state that the washing solution based on 2.4 % HES and 4.2 % HSA is equivalent to that used in our routine practice. Therefore, we could use the solution with HES, paying special attention to the renal function of the recipient.


Glycyrrhizic acid nanoparticles inhibit LPS-induced inflammatory mediators in 264.7 mouse macrophages compared with unprocessed glycyrrhizic acid.
Glycyrrhizic acid (GA), the main component of radix glycyrrhizae, has a variety of pharmacological activities. In the present study, suspensions of GA nanoparticles with the average particle size about 200 nm were prepared by a supercritical antisolvent (SAS) process. Comparative studies were undertaken using lipopolysaccardide (LPS)-stimulated mouse macrophages RAW 264.7 as in vitro inflammatory model. Several important inflammation mediators such as NO, PGE2, TNF-α and IL-6 were examined. These markers were highly stimulated by LPS and were inhibited both by nano-GA and unprocessed GA in a dose-dependent manner, especially PGE2 and TNF-α. However nano-GA and unprocessed GA inhibited NO only at a high concentration. In general, we found that GA nanoparticle suspensions exhibited much better anti-inflammatory activities compared to unprocessed GA.


Food availability affects growth in a coral reef fish.
Pomacentrus amboinensis is common on small patch reefs within One Tree Lagoon (Great Barrier Reef), where it preferentially settles onto deep reefs. A preliminary experiment, in which juveniles were transplanted to identical reef structures at two sites, within two depth strata, indicated that juvenile growth and survivorship were better in deeper water. The hypothesis that this difference was due to food availability was tested by a supplemental feeding experiment, carried out at another two randomly chosen sites, within the same two depth strata. Fish were fed each day over a one month period, during which no mortality was observed. The growth rates of juveniles were markedly higher on all food-supplemented reefs, when compared to controls. Growth differed between depth strata, but there was no interaction between the food x depth factors, which would have suggested a greater effect of food supplementation in either habitat. Thus, although the difference between depths cannot be attributed to food availability, the results have a more general significance. Food appears to be a limiting resource (in terms of growth) in both the marginal shallow habitat, and the more suitable deeper habitat.


Respiratory function after birth in infants with congenital diaphragmatic hernia.
To characterise the transitional pulmonary physiology of infants with congenital diaphragmatic hernia (CDH) using measures of expiratory tidal volume (TV) and end-tidal carbon dioxide (ETCO2). Prospective single-centre observational study. Quaternary neonatal intensive care unit. Infants with an antenatal diagnosis of CDH born at the Children's Hospital of Philadelphia. TV and ETCO2 were simultaneously recorded using a respiratory function monitor (RFM) during invasive positive pressure ventilation immediately after birth. TV per birth weight and ETCO2 values were summarised for each minute after birth. Subgroups of interest were defined by liver position (thoracic vs abdominal) and extracorporeal membrane oxygenation (ECMO) treatment. RFM data were available for 50 infants from intubation until a median (IQR) of 9 (7-14) min after birth. TV and ETCO2 values increased for the first 10 min after birth, but intersubject values were heterogeneous. TVs were overall lower and ETCO2 values higher in infants with an intrathoracic liver and infants who were ultimately treated with ECMO. On hospital discharge, survival was 88% (n=43) and 34% (n=17) of infants were treated with ECMO. Respiratory function immediately after birth is heterogeneous for infants with CDH. Lung aeration, as evidenced by expired TV and ETCO2, appears to be ongoing throughout the first 10 min after birth during invasive positive pressure ventilation. Close attention to expired TV and ETCO2 levels by 10 min after birth may provide an opportunity to optimise and individualise ventilatory support for this high-risk population.


[Application of homologous tendons and ligaments (author's transl)].
The report deals with the postoperative results of homologous cialit-preserved tendons and ligaments in 237 patients with 281 homologous cialit-preserved transplants. This material proved to be equally effective to the autologous and even superior to it when grafting flexor tendons of the finger. 4.7% disturbed woundhealing, 5.2% infections, 5.5% mechanical insufficiency.


[Observations of ultrastructural changes on prepared homologous tendon transplants in humans (author's transl)].
Authors have investigated the ultrastructural morphology of transformation of homologous human tendon transplants. Tenoblasts and mast cells were found next to collagenous fibres originating in the transplant and disintegrating in the voluminous ground substance. The formation of new collagen tissue was of different grades; areas of only a few fibres and areas with oriented fibres were both present. Twenty months after implantation parts characterised by apparently mature structure were found as well as abundant new fibre formation and mast cells.


24-hour movement guideline adherence and mental health: A cross-sectional study of emerging adults with chronic health conditions and disabilities.
Recent work has shown that individuals with chronic health conditions and disabilities (CCD) meet the 24-h movement guidelines at lower rates than population norms; however, the evidence base remains limited across different stages of the lifespan and very few studies have examined associations with mental health outcomes. This study examined 24-h movement guideline adherence among emerging adults with CCD compared to those without and associations between guideline adherence and indicators of mental health. This cross-sectional study used data from the 2020 cycle of the Canadian Campus Wellbeing Survey. A total of 17,874 emerging adults enrolled at 20 post-secondary institutions (mean age = 21.6 ± 2.94 years; 65.2% female), including 3336 who identified with a CCD, self-reported their movement behaviors (physical activity, sedentary behaviors, sleep) and completed measures of psychological distress and mental well-being. Logistic regressions models were computed to examine differences in guideline adherence. Propensity score weighted linear regression models were computed to examine associations between guideline adherence and indicators of mental health. Emerging adults with CCD had significantly lower odds of meeting the 24-h movement guidelines than their peers, and disparities in guideline adherence were most pronounced among those with multimorbidity, developmental, and physical disabilities. Guideline adherence was associated with significantly more favorable scores for psychological distress and mental well-being among those with and without CCD. Findings suggest emerging adults with CCD engage in less healthy movement behavior patterns than their peers, yet they appear to experience similar mental health benefits when they do meet the 24-h movement guidelines.


Real life experience on the effect of Belimumab in patients with active systemic lupus.
To evaluate real life experience on the effect of Belimumab in patients with active systemic lupus erythematosus. Twenty patinets with musclesketal symptoms were evaluated, three were discontinued for different resons and seventeen completed eight injections of Belimumab during a six month period. A fatigue score was also evaluated at the same time. Marked reduction of disease activity and fatigue score were observed in the patient group. Belimumab is a novel form of therapy in patients with active systemic lupus erythematosus to be added in the standard of care particularly in patients with skin and joint symptoms.


Nerve root sedimentation sign for the diagnosis of lumbar spinal stenosis: reliability, sensitivity, and specificity.
Retrospective review of magnetic resonance images. Examine the diagnostic accuracy, discriminative ability, and reliability of the sedimentation sign in a sample of patients with clinically diagnosed lumbar spinal stenosis (LSS), low back pain (LBP), and vascular claudication, and in asymptomatic controls. The nerve root sedimentation sign (SedSign) was recently described as a new diagnostic test for LSS; however, the degree to which this sign is sensitive and specific in diagnosis of LSS is unknown. All LSS images were obtained from subjects who had clinically diagnosed LSS confirmed on imaging by a spine specialist. The other images were obtained from people with LBP but no LSS, people with severe vascular claudication, and asymptomatic participants. Three blinded raters independently assessed the images. A positive sign was defined as the absence of nerve root sedimentation at the level above or below the level of maximum stenosis. Images from 148 subjects were reviewed (67 LSS, 31 LBP, 4 vascular, and 46 asymptomatic). Intrarater reliability for the sign ranged from κ= 0.87 to 0.97 and inter-rater reliability from 0.62 to 0.69. Sensitivity ranged from 42% to 66%, and specificity ranged from 49% to 78%. Sensitivity improved to a range of 60% to 96% when images with only a smallest cross-sectional area of the dural sac less than 80 mm were included. The sign was able to differentiate (P = 0.004) between LSS and asymptomatic controls but not between LSS and LBP or between LSS and vascular claudication. The SedSign was shown to have high intrarater reliability and acceptable inter-rater reliability. The Sign appears most sensitive in defining severe LSS cases, yet may not aid in the differential diagnosis of LSS from LBP or vascular claudication, or add any specific diagnostic information beyond the traditional history, physical examination, and imaging studies that are standard in LSS diagnosis. 4.


On the metabolism of GM3 ganglioside in cultured human foreskin fibroblasts.
The metabolism of GM3 ganglioside in cultured human foreskin fibroblasts was investigated by labeling cultured cells with [1-3H]-galactose for 48 hours, followed by a 48 hour chase. More than 80% of the radioactivity associated with GM3 was found in the hexose portion of the carbohydrate chain, whereas approximately 12% of the radioactivity was observed in the sialic acid moiety. The hexose and sialic acid residues lost 42% and 53% of their initial radioactivity, respectively, during the chase period, indicating an active metabolism of these sugar residues of GM3 in growing cultures.


Dendritic cells in cutaneous, lymph node and pulmonary lesions of sarcoidosis.
To determine whether dendritic cells (DC) are a consistent feature of lesions of sarcoidosis, we have used monoclonal antibodies to identify the HLA-DR-expressing populations of cells in cryostat sections of 15 lymph node, pulmonary and cutaneous lesions. The commonest HLA-DR positive cells in granulomas were epithelioid and giant cells, although lymphocytes within granulomas and tissue macrophages around them were also positive. Dendritic cells with Langerhans cells (NA1/34+ = OKT6+) and interdigitating cell (RFD1+) phenotype were consistently associated with granulomas only in skin lesions. In lymph nodes, interdigitating cells (NA1/34-/RFD1+/HLA-DR++) were confined to paracortical zones as in normal nodes, although a small area of NA1/34+/RFD1+ cells was found in one of three nodes. In lung lesions NA1/34+/RFD1+ dendritic cells were uncommon or absent, except in one chronic case. We conclude that while sometimes present in extracutaneous sites, DC are not an essential feature of sarcoid lesions, and that cells of the classical macrophage group are the most significant HLA-DR-expressing population. We suggest that the presence of DC in lesions of sarcoidosis may indicate an immunological response distinct from that causing granulomas to form. The variability of their involvement may have immunoregulatory significance.


Computerised tomography-based planning with conventional total hip arthroplasty versus robotic-arm assisted total hip arthroplasty: study protocol for a prospective randomised controlled trial.
Robotic-arm assisted surgery aims to reduce manual errors and improve the accuracy of implant positioning during total hip arthroplasty. The objective of this study is to compare the accuracy of implant positioning, restoration of hip biomechanics, patient satisfaction, functional outcomes, implant survivorship, cost-effectiveness, and complications in conventional manual total hip arthroplasty (CO THA) versus robotic-arm assisted total hip arthroplasty (RO THA). Preoperative pelvic computerised tomography (CT) scans will be used to create patient-specific, virtual, three-dimensional reconstructions for surgical planning in both treatment groups. This prospective randomised controlled trial will include 60 patients with symptomatic hip osteoarthritis undergoing primary THA. Following informed consent, patients will be randomised to CO THA (control group) or RO THA (investigation group) at a ratio of 1:1 using an online random number generator. Observers will review patients at regular intervals for 2 years after surgery to record predefined study outcomes relating to the accuracy of implant positioning, hip biomechanics, postoperative rehabilitation, clinical progress, functional outcomes, cost-effectiveness, and complications. Primary and secondary objectives will be used to quantify and draw inferences on differences in the efficacy of treatment between the two groups. Intention-to-treat and per-protocol population analysis will be undertaken. Intention to treat relates to the allocated treatment (CO THA or RO THA), and per-protocol refers to the actual treatment received by the patient. The following statistical methods will be employed to analyse the data: descriptive statistics, independent t test, paired t test, analysis of variance, Fisher exact test, chi-square test, and graphical displays. Ethical approval was obtained from the London-Bromley Research Ethics Committee, UK. The study is sponsored by University College London, UK. This study compares a comprehensive and robust range of clinical, functional, and radiological outcomes in CT-planned CO THA versus CT-planned RO THA. The findings of this study will enable an improved understanding of the differences in CO THA versus RO THA with respect to patient satisfaction, functional outcomes, implant survivorship, cost-effectiveness, and complications. ClinicalTrials.gov NCT04095845 . Registered on 19 September 2019.


Mental health disorders in home care elders: An integrative review.
Home care is the fastest growing U.S. health care sector, serving a predominance of highly vulnerable elderly patients. Mental health disorders (MHDs) are a major health concern in this population, however, current knowledge regarding their occurrence and associated correlates is inadequate. To address this gap, this integrative review examined existing findings regarding the prevalence and correlates of MHDs in home care elders. A search of six electronic databases and a hand search produced a final group of 36 articles for review. Poor data representativeness and methodological limitations impacted the quality of these studies, as reflected in an extremely wide range of prevalence estimates for these disorders (12% - 62%). A number of recommendations are made with respect to future research in this area. These include conducting multi-site investigations and the use of consistent and clear protocols for identification of MHDs in home care elders, a growing and significantly under-served population.


Heavy chain diseases.
Heavy chain diseases (HCDs) are rare B-cell lymphoplasma-cell proliferative disorders characterized by production of truncated monoclonal immunoglobulin heavy chains without associated light chains. HCDs involving the three main immunoglobulin classes have been described; alpha-HCD is the most common and has the most uniform presentation, gamma- and mu-HCDs have variable clinical presentations and histopathologic features. HCDs can be thought of as variant types of non-Hodgkin lymphoma: alpha-HCD presents as an extranodal marginal-zone lymphoma of mucosa-associated lymph-node tissue, gamma-HCD as lymphoplasmacytoid non-Hodgkin lymphoma, and mu-HCD as small lymphocytic non-Hodgkin lymphoma or chronic lymphocytic leukemia. Diagnosis of HCD requires documentation of a deleted immunoglobulin heavy chain without a bound light chain in the serum or urine. Prognosis is variable, and no standardized effective treatment programs are available except for alpha-HCD, which in its early stage may respond to antibiotics.


Microtubules are involved in anterior-posterior axis formation in C. elegans embryos.
Microtubules deliver positional signals and are required for establishing polarity in many different organisms and cell types. In Caenorhabditis elegans embryos, posterior polarity is induced by an unknown centrosome-dependent signal. Whether microtubules are involved in this signaling process has been the subject of controversy. Although early studies supported such an involvement (O'Connell, K.F., K.N. Maxwell, and J.G. White. 2000. Dev. Biol. 222:55-70; Wallenfang, M.R., and G. Seydoux. 2000. Nature. 408:89-92; Hamill, D.R., A.F. Severson, J.C. Carter, and B. Bowerman. 2002. Dev. Cell. 3:673-684), recent work involving RNA interference knockdown of tubulin led to the conclusion that centrosomes induce polarity independently of microtubules (Cowan, C.R., and A.A. Hyman. 2004. Nature. 431:92-96; Sonneville, R., and P. Gonczy. 2004. Development. 131: 3527-3543). In this study, we investigate the consequences of tubulin knockdown on polarity signaling. We find that tubulin depletion delays polarity induction relative to wild type and that polarity only occurs when a small, late-growing microtubule aster is visible at the centrosome. We also show that the process of a normal meiosis produces a microtubule-dependent polarity signal and that the relative levels of anterior and posterior PAR (partitioning defective) polarity proteins influence the response to polarity signaling. Our results support a role for microtubules in the induction of embryonic polarity in C. elegans.


New perspectives in cancer: Modulation of lipid metabolism and inflammation resolution.
Inflammation is considered an enabling feature of cancer. Besides the persistence of inflammatory stimuli, also defective mechanisms of resolution can lead to chronic inflammation. Inflammation resolution is an active process controlled by lipidic specialized pro-resolving mediators (SPMs), derived from ω-3 or ω-6 essential polyunsaturated fatty acids (PUFA) through the activity of lipoxygenases (ALOX5 and 15). Thus, a lack or defect in resolution mechanisms may affect cancer development and progression by prolonging inflammation. Components of pro-resolving pathways (PUFA, enzymes, or SPMs) have been reported to modulate various cancer features by affecting both cancer cells and cancer-associated stroma. Here, we will review the most important mechanisms by which SPMs, ω-3/6 PUFA, and ALOXs affect cancer biology, paying particular attention to their role in the inhibition of inflammation and angiogenesis, two of the most important hallmarks of cancer. The collection of these results may suggest novel perspectives in cancer management based on the modulation of lipid metabolism and the production of SPMs.


[Continuous lumbar epidural anesthesia: insertion a patient with unrecognized classical hemophilia A].
This report describes a case where a continuous lumbar epidural anesthesia was inserted for an operation in a patient with classical hemophilia which was unknown at the time of catheter insertion. In addition to an exact description of the intervention, the anamnesis and laboratory contraindications for epidural anesthesia are discussed. Furthermore, the necessity of preoperative investigations and their value when an epidural anesthesia is planned are also discussed.


Involvement of CD56/N-CAM molecule in the adhesion of human solid tumor cell lines to endothelial cells.
Tumor-endothelial cell adhesion has been investigated, as this event might represent one of the first steps in the generation of tumor metastasis. We focused our attention on the N-CAM homologous CD56 (besides the CD44, CD15, and CDw49d antigens), as we have recently reported that it can mediate lymphocyte-endothelial cell adhesion [11]. Herein we show that CD56 is involved in tumor cell-endothelial cell binding. This phenomenon is independent of Ca2+ and unlikely to be influenced by the degree of CD56 sialylation.


Ciliogenesis in submersion and suspension cultures of human nasal epithelial cells.
Human nasal respiratory cells lose cilia in submerged cultures. This study compares the effect of extracellular matrix (ECM) molecules of the basal lamina on ciliogenesis in submerged cell cultures to ECM-free suspension cultures. Respiratory mucosa of nasal turbinates was the routine source for the cultures of nasal epithelial cells. For the submersion cultures, enzymatically isolated cells were seeded either on a layer of lethally irradiated ((60)Co, 60 Gy) murine 3T3-feeder fibroblasts or on an ECM-coated culture flask. For suspension cultures, the flasks were rotated for 3 days after cell seeding. In ECM-coated flasks, epithelial cell attachment and confluence was promoted and always much better than in cultures on a feeder layer. Respiratory cells lost cilia during the first 5 weeks in submerged cultures. Genesis of new, actively beating cilia was seen after 5-6 weeks when plastic culture dishes were coated with ECM molecules. Cells grown on uncoated plastic dishes together with 3T3-fibroblasts showed no ciliogenesis. Spheroids of epithelial cells in suspension cultures lost cilia during the 1st week and developed new cilia after 1-2 weeks in vitro. Our results suggest that ECM molecules are not the only signal for ciliary differentiation of respiratory cells in vitro, because suspension cultures are ECM free. However, the presence of ECM molecules in submerged cell cultures promotes the attachment and early confluence of seeded epithelial cells with a high density of cuboidal epithelial cells. The specific cellular shape and intense intercellular contact of these cuboidal cells may be among the most important signals inducing terminal differentiation and ciliogenesis.


Cough Severity Index in Brazilian Portuguese: Translation and Cross-Cultural Adaptation.
To translate and cross-culturally adapt the Cough Severity Index to Brazilian Portuguese. This is a study with observational, cross-sectional, and analytical design. The procedure for translation and cross-cultural adaptation followed the recommendations of the Scientific Advisory Committee of the Medical Outcomes Trust and was performed in five stages: translation, synthesis, back translation, committee review, and pretesting. The sample for the pretest consisted of 34 participants with refractory chronic cough, 11 males and 23 females, with an average age of 48 years and 1 month. The title of the questionnaire, the answer options, and seven of the ten questions were agreed upon by three judges, the remaining three questions were retranslated by a fourth judge. After back-translation and committee review, editing of question five was necessary. The option "never" was more frequently selected for four questions and the option "always" for six questions. There was a significantly higher proportion of other response categories of the instrument compared to the response category "not applicable." This study resulted in the elaboration of a translated and cross-culturally adapted version of the Cough Severity Index in Brazilian Portuguese.


[Coagulopathy and thrombosis: similarities and differences among pathogenic coronaviruses].
One of the most significant negative prognostic factors in patients suffering from the disease caused by SARS-CoV-2 (COVID-19) is the development of coagulopathy, associated with abnormal laboratory findings, such as increased D-dimer, and venous thromboembolic complications, requiring thromboprophylactic strategies. The main clinical characteristics of COVID-19 patients are revised here as compared to other coronavirus infections, such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), emphasizing clinical, diagnostic and therapeutic aspects.


Influence of web traits, height, and daily periods of exposition on prey captured by orb-weaver spiders.
Orb-webs show diversity in several traits, including silk types, architecture, physical properties, locale, and period of exposition. The investigation of how they determine the identity of intercepted prey is important to functional ecology and to the evaluation of trophic niche partitioning within communities. However, the influence of several of these variables on the composition of intercepted insects remains to be determined. In this study, we evaluated the effects of web architectural traits, height, and daily periods of exposition on the interception of different insects in terms of sizes, masses, and taxa. We conducted observations of prey intercepted by the orb webs of 16 sympatric spider species and artificial webs. We found that all orb webs mainly intercepted small and light insects, sharing the most abundant insect families found in the study area. However, spiders that show nocturnal activity, more radii in their webs, large and high webs captured heavier insects. Other orb-web traits, such as the density of capture threads did not influence the kind of intercepted insects. We discuss why some variables affected prey interceptions in terms of mass. Finally, we discuss the implications of these influential variables to functional ecology, niche differentiation, and how behavioral assessments can complete this investigation in future studies.


Modeling the Complete Gravitational Wave Spectrum of Neutron Star Mergers.
In the context of neutron star mergers, we study the gravitational wave spectrum of the merger remnant using numerical relativity simulations. Postmerger spectra are characterized by a main peak frequency f2 related to the particular structure and dynamics of the remnant hot hypermassive neutron star. We show that f(2) is correlated with the tidal coupling constant κ(2)^T that characterizes the binary tidal interactions during the late-inspiral merger. The relation f(2)(κ(2)^T) depends very weakly on the binary total mass, mass ratio, equation of state, and thermal effects. This observation opens up the possibility of developing a model of the gravitational spectrum of every merger unifying the late-inspiral and postmerger descriptions.


Mohs micrographic surgery for skin cancer.
Mohs micrographic surgery is a reliable outpatient surgical method of removing skin cancer. The method includes tissue excision in thin layers, colour-coding of excised specimens, accurate orientation of excised tissue through construction of tissue maps, and microscopic examination of horizontal frozen sections. Selected basal and squamous cell carcinomas are treated most commonly by this method, however, a variety of less common tumors are also amenable to treatment. Mohs micrographic surgery offers the highest cure rates for selected malignancies while maintaining maximal preservation of normal tissue and important anatomic structures.


[The effect of Galla chinensis on the demineralization of enamel].
To investigate the effect of Galla Chinensis with or without fluoride on demineralization of enamel. Galla Chinensis with or without fluoride and acid buffer were used to treat the samples alternately and the treatment was repeated 8 times. Then the calcium of acid buffer was measured by American PE HTS 7000 plus and the specimens were observed with laser scanning confocal microscope. Compared with the calcium concentration of control group (deionized water or fluoride), the calcium concentration of all tested groups (except the 1 mg/ml group without fluoride) decreased significantly (P < 0.25). There was marked difference in total fluorescence (TF) and average fluorescence (AF) between the tested groups and control group (P < 0.05). As for the area of lesion, only groups without fluoride and the 4 mg/ml group containing fluoride decreased (P < 0.01). Confocal images showed that the zone of red area of tested groups was narrower than that of control group. Galla Chinensis can reinforce the resistance of enamel to acid, either with or without fluoride.