GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3.
While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.


Dental anomalies inside the cleft region in individuals with nonsyndromic cleft lip with or without cleft palate.
Individuals with nonsyndromic cleft lip with or without cleft palate (NSCL±P) present high frequency of dental anomalies, which may represent complicating factors for dental treatment. The aim of this study was to investigate the prevalence of dental anomalies inside cleft area in a group of Brazilians with NSCL±P. Retrospective analysis of 178 panoramic radiographs of patients aged from 12 to 45 years old and without history of tooth extraction or orthodontic treatment was performed. Association between cleft type and the prevalence of dental anomalies was assessed by chi-square test with a significance level set at p≤ 0.05. Dental anomalies were found in 88.2% (n=157) of the patients. Tooth agenesis (47.1%), giroversion (20%) and microdontia (15.5%) were the most common anomalies. Individuals with unilateral complete cleft lip and palate (CLP, p<0.0001), bilateral complete CLP (p=0.0002) and bilateral incomplete CLP (p< 0.0001) were more affected by tooth agenesis than individuals with other cleft types. The maxillary lateral incisors were the most affected teeth (p<0.0001). The present study revealed a high frequency of dental anomalies inside cleft region in NSCL±P patients, and further demonstrated that patients with unilateral complete CLP and bilateral incomplete CLP were frequently more affected by dental anomalies. Moreover, our results demonstrate that dental anomalies should be considered during dental treatment planning of individuals affected by NSCL±P.


Xanthine-induced deficits in hippocampal behavior and abnormal expression of hemoglobin genes.
The prevalence of mental disorders such as depression and anxiety is high and often comorbid with other diseases. Chronic stress is a common risk factor for these disorders, but the mechanisms behind their development are not yet fully understood. Metabolomics has revealed a close association between purine and pyrimidine metabolism and depression and anxiety, with increased levels of serum xanthine observed in both humans and mice. Xanthine is known as purine metabolism, and this compound shows several biological activities, but the impact of xanthine on our brain function is still unclear. The hippocampus, which plays a crucial role in memory and learning, is also implicated in the pathophysiology of depression and anxiety. Here, we investigated the effects of xanthine intraperitoneal administration on spatial memory and anxiety-like behavior in mice. The findings indicated that xanthine administration induced a deficit of hippocampus-dependent spatial memory and a tendency to anxiety-like behavior in mice. RNA-seq analysis showed that xanthine administration upregulated hemoglobin (Hb) genes involved in oxygen transport in the hippocampus. The upregulated Hb genes occurred in the neuronal cells, and in vitro experiments revealed that both Hba-a1 derived from mice and HBA2 derived from humans were upregulated by xanthine treatment. These observations suggest that the xanthine-induced Hb in the hippocampus could be related to spatial memory deficit and anxiety. This study sheds light on the direct effects of xanthine on the brain and its potential role in the development of depression and anxiety symptoms caused by chronic stress.


Docking studies reveal a selective binding of D-penicillamine to the transactivator protein of human immunodeficiency virus type 1.
DOCK and Affinity studies were carried out to study the binding of D- and L-penicillamine to the transactivator protein (tat) of human immunodeficiency virus type 1 (HIV-1). These studies reveal a selective binding of D-penicillamine to the cysteine-rich region covering amino acid residues 20-38 of the tat protein. A careful analysis of the components of the binding energy of the D- and L-isomers reveals that the D-isomer has a more favorable van der Waals interaction resulting from an optimal placement of the dimethylthiomethyl side chain in the binding site. This observation matches the experimental data that D-penicillamine is a more potent inhibitor of tat-mediated transactivation than the L-isomer. The docking and experimental data offer an interesting approach to design structural molecules with potential application to block signal functions of the tat protein in HIV-1 pathogenesis.


Analysis of cerebral defective states acquired in early life.
The clinical and radiographic data provided by CT of 34 patients with cerebral defects acquired in early life were analyzed. Seventeen patients showed porus-like defects due to vascular thrombosis. Volume measurements were made in 26 patients to determine tissue loss and volume shifting by ROI. CT is the most effective means of detecting the cause of the lesion.


Capillary K+-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow.
Blood flow into the brain is dynamically regulated to satisfy the changing metabolic requirements of neurons, but how this is accomplished has remained unclear. Here we demonstrate a central role for capillary endothelial cells in sensing neural activity and communicating it to upstream arterioles in the form of an electrical vasodilatory signal. We further demonstrate that this signal is initiated by extracellular K+ -a byproduct of neural activity-which activates capillary endothelial cell inward-rectifier K+ (KIR2.1) channels to produce a rapidly propagating retrograde hyperpolarization that causes upstream arteriolar dilation, increasing blood flow into the capillary bed. Our results establish brain capillaries as an active sensory web that converts changes in external K+ into rapid, 'inside-out' electrical signaling to direct blood flow to active brain regions.


Signaling pathways driving ocular malignancies and their targeting by bioactive phytochemicals.
Ocular cancers represent a rare pathology. The American Cancer Society estimates that 3,360 cases of ocular cancer occur annually in the United States. The major types of cancers of the eye include ocular melanoma (also known as uveal melanoma), ocular lymphoma, retinoblastoma, and squamous cell carcinoma. While uveal melanoma is one of the primary intraocular cancers with the highest occurrence in adults, retinoblastoma remains the most common primary intraocular cancer in children, and squamous cell carcinoma presents as the most common conjunctival cancer. The pathophysiology of these diseases involves specific cell signaling pathways. Oncogene mutations, tumor suppressor mutations, chromosome deletions/translocations and altered proteins are all described as causal events in developing ocular cancer. Without proper identification and treatment of these cancers, vision loss, cancer spread, and even death can occur. The current treatments for these cancers involve enucleation, radiation, excision, laser treatment, cryotherapy, immunotherapy, and chemotherapy. These treatments present a significant burden to the patient that includes a possible loss of vision and a myriad of side effects. Therefore, alternatives to traditional therapy are urgently needed. Intercepting the signaling pathways for these cancers with the use of naturally occurring phytochemicals could be a way to relieve both cancer burden and perhaps even prevent cancer occurrence. This research aims to present a comprehensive review of the signaling pathways involved in various ocular cancers, discuss current therapeutic options, and examine the potential of bioactive phytocompounds in the prevention and targeted treatment of ocular neoplasms. The current limitations, challenges, pitfalls, and future research directions are also discussed.


The validity of the Hospital Anxiety and Depression Scale. An updated literature review.
To review the literature of the validity of the Hospital Anxiety and Depression Scale (HADS). A review of the 747 identified papers that used HADS was performed to address the following questions: (I) How are the factor structure, discriminant validity and the internal consistency of HADS? (II) How does HADS perform as a case finder for anxiety disorders and depression? (III) How does HADS agree with other self-rating instruments used to rate anxiety and depression? Most factor analyses demonstrated a two-factor solution in good accordance with the HADS subscales for Anxiety (HADS-A) and Depression (HADS-D), respectively. The correlations between the two subscales varied from.40 to.74 (mean.56). Cronbach's alpha for HADS-A varied from.68 to.93 (mean.83) and for HADS-D from.67 to.90 (mean.82). In most studies an optimal balance between sensitivity and specificity was achieved when caseness was defined by a score of 8 or above on both HADS-A and HADS-D. The sensitivity and specificity for both HADS-A and HADS-D of approximately 0.80 were very similar to the sensitivity and specificity achieved by the General Health Questionnaire (GHQ). Correlations between HADS and other commonly used questionnaires were in the range.49 to.83. HADS was found to perform well in assessing the symptom severity and caseness of anxiety disorders and depression in both somatic, psychiatric and primary care patients and in the general population.


Mediterranean, DASH, and MIND Dietary Patterns and Cognitive Function: The 2-Year Longitudinal Changes in an Older Spanish Cohort.
Background and Aims: Plant-forward dietary patterns have been associated with cardiometabolic health benefits, which, in turn, have been related to cognitive performance with inconsistent findings. The objective of this study was to examine the relationship between baseline adherence to three a priori dietary patterns (Mediterranean, DASH, and MIND diets) with 2-year changes in cognitive performance in older adults with overweight or obesity and high cardiovascular disease risk. Methods: A prospective cohort analysis was conducted within the PREDIMED-Plus trial, involving 6,647 men and women aged 55-75 years with overweight or obesity and metabolic syndrome. Using a validated, semiquantitative 143-item food frequency questionnaire completed at baseline, the dietary pattern adherence scores were calculated. An extensive neuropsychological test battery was administered at baseline and 2-year follow-up. Multivariable-adjusted linear regression models were used to assess associations between 2-year changes in cognitive function z-scores across tertiles of baseline adherence to the a priori dietary patterns. Results: Adherence to the Mediterranean diet at baseline was associated with 2-year changes in the general cognitive screening Mini-Mental State Examination (MMSE, β: 0.070; 95% CI: 0.014, 0.175, P-trend = 0.011), and two executive function-related assessments: the Trail Making Tests Part A (TMT-A, β: -0.054; 95% CI: -0.110, - 0.002, P-trend = 0.047) and Part B (TMT-B, β: -0.079; 95% CI: -0.134, -0.024, P-trend = 0.004). Adherence to the MIND diet was associated with the backward recall Digit Span Test assessment of working memory (DST-B, β: 0.058; 95% CI: 0.002, 0.114, P-trend = 0.045). However, higher adherence to the DASH dietary pattern was not associated with better cognitive function over a period of 2 years. Conclusion: In older Spanish individuals with overweight or obesity and at high cardiovascular disease risk, higher baseline adherence to the Mediterranean dietary pattern may be associated with better cognitive performance than lower adherence over a period of 2 years.


Quercetin synergistically potentiates the anti-metastatic effect of 5-fluorouracil on the MDA-MB-231 breast cancer cell line.
Breast cancer (BC) cells' ability to metastasize to other tissues increases mortality. The Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) facilitate cancer cell migration. 5-fluorouracil is a frequently applied chemotherapeutic agent in cancer treatment with destructive side effects on normal tissues. Hence, researchers have focused on finding a way to reduce the dose of chemotherapeutic drugs. Quercetin, a natural polyphenolic compound, has inhibitory effects on proliferation and migration of tumor cells. This study evaluated the effect of the combination of Quercetin and 5-fluorouracil on migration of the MDA-MB-231 breast cancer cell line. The effect of Quercetin, 5-fluorouracil , and their combination on MDA-MB-231 breast cancer cell proliferation was investigated through MTT assay. Inhibition of tumor cell migration was examined by wound healing assay. Finally, the effect of treatments on gene expression of MMP-2 and MMP-9 was evaluated by quantitative real-time PCR. The IC50 values for Quercetin and 5-fluorouracil after 48 hr treatment were 295 μM and 525 μM, respectively. The combination index (CI) for Quercetin and 5-fluorouracil was <1, indicating synergy between them. The combination of Quercetin plus 5-fluorouracil resulted in a significant reduction in migration rate and MMP-2 and MMP-9 gene expressions of MDA-MB-231 cancer cells compared with the individual application of 5-FU. Quercetin enhances the suppressory effect of 5-fluorouracil on migration of BC cells. The combination of Quercetin and 5-fluorouracil can be an attractive field for future studies.


[A rare cause of oral pain: The pterygoid hamulus syndrome].
Pterygoid hamulus syndrome (PHS) is a rare cause of orofacial and oropharyngeal pain. PHS can be associated with a hamulus hypertrophy or with a bursitis of the palatosalpingeus but it has not always an anatomic cause. A 36-year-old woman was seen for a constant posterior palatal pain spreading towards oropharynx, increasing during swallowing and lasting for more than 6 months. Physical examination showed an erythema of the soft palate, medially to the hamulus. Hamulus palpation was painful and revealed hamulus hypertrophia on both sides. A bilateral PHS was evocated. This observation is typical of a PHS. We propose a review of the literature of this little-known syndrome. Treatment is initially conservative (corticosteroids) but surgery can be proposed in case of morphological anomalies of the hamulus.


Multi-party computation mechanism for anonymous equity block trading: A secure implementation of turquoise plato uncross.
Dark pools are financial trading venues where orders are entered and matched in secret so that no order information is leaked. By preventing information leakage, dark pools offer the opportunity for large volume block traders to avoid the costly effects of market impact. However, dark pool operators have been known to abuse their privileged access to order information. To address this issue, we introduce a provably secure multi-party computation mechanism that prevents an operator from accessing and misusing order information. Specifically, we implement a secure emulation of Turquoise Plato Uncross, Europe's largest dark pool trading mechanism, and demonstrate that it can handle real world trading throughput, with guaranteed information integrity.


Genetic diversity, phylogroup distribution and virulence gene profile of pks positive Escherichia coli colonizing human intestinal polyps.
Some Escherichia coli strains of phylogroup B2 harbor a (pks) pathogenicity island that encodes a polyketide-peptide genotoxin called colibactin. It causes DNA double-strand breaks and megalocytosis in eukaryotic cells and it may contribute to cancer development. Study of bacterial community that colonizes the adenomatous polyp lesion, defined as precancerous lesions, could be helpful to assess if such pathogenic bacteria possess a role in the polyp progression to cancer. In this cross-sectional study, a total of 1500 E. coli isolates were obtained from biopsies of patients presenting adenomatous colon polyps, the normal tissues adjacent to the polyp lesion and patients presenting normal mucosa. pks island frequency, phylogenetic grouping, fingerprint genotyping, and virulence gene features of pks positive (pks+) E. coli isolates were performed. We found pks+E. coli strongly colonize two patients presenting polypoid lesions and none were identified in patients presenting normal mucosa. Predominant phylogroups among pks+E. coli isolates were B2, followed by D. Clustering based on fragment profiles of composite analysis, typed the pks+ isolates into 5 major clusters (I-V) and 17 sub-clusters, demonstrating a high level of genetic diversity among them. The most prevalent virulence genes were fimH and fyuA (100%), followed by vat (92%), hra and papA (69%), ibeA (28%), and hlyA (25%). Our results revealed that pks+E. coli can colonize the precancerous lesions, with a high distribution in both the polyp lesions and in normal tissues adjacent to the lesion. The high differences in fingerprinting patterns obtained indicate that pks+E. coli strains were genetically diverse, possibly allowing them to more easily adapt to environmental variations.


Autoimmune thyroid disease susceptibility loci in a large Chinese family.
The autoimmune thyroid diseases (AITDs) comprising Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases, which result from an interaction between predisposing genes and environmental triggers. The aim of our study was to dissect the genetic predisposition to GD and HT in one large Chinese family with multiple members affected with AITD. We completed a whole genome screen of a large multiplex Chinese-American family. We enrolled 27 family members from three generations. Eight members were affected with AITD, six had GD and two had HT. We determined the information limits of the family. Power calculations indicated that the maximum attainable LOD scores were 5.1 assuming dominant inheritance, and 3.4 assuming recessive inheritance. These estimates both assumed 100% penetrance and one gene. Whole genome screening was performed using 400 highly polymorphic and densely spaced microsatellite markers spanning the entire human genome (intermarker distance < 10 cM). Linkage analysis was performed using two-point and multipoint parametric and nonparametric methods. Initial whole genome screening performed with 400 microsatellite markers identified two markers that showed evidence for linkage to AITD in this family, D11S4191 and D9S175, with two-point LOD scores of 2.31 and 2.05, respectively. Multipoint linkage analysis focusing on the regions containing these markers revealed a maximum multipoint LOD score (MLS) of 2.13 and a nonparametric linkage score (NPL) of 6.1 for D11S4191 and an MLS of 2.01 and NPL of 7.5 for D9S175. These results showed that this Chinese family harboured susceptibility loci for AITD which were distinct from those previously found in the Caucasian population. This suggests that different susceptibility loci exist between different ethnic groups. Furthermore, even within a single family from a genetically homogenous population, more than one gene was involved in the genetic susceptibility to AITD, supporting the notion that AITDs are caused by multiple genes of varying influences.


Prostanoid-induced contraction of human bronchial smooth muscle is mediated by TP-receptors.
1. A range of naturally-occurring prostaglandins sulprostone, 16,16-dimethyl prostaglandin E2 (DME2) and the thromboxane A2 (TXA2)-mimetic, 11 alpha,9 alpha-epoxymethano prostaglandin H2 (U-46619) have been tested for contractile agonist activity on human isolated bronchial smooth muscle. 2. Prostaglandin D2 (PGD2), PGF2 alpha, 9 alpha,11 beta-PGF2 (11 beta-PGF2) and U-46619 all caused concentration-related contractions. U46619 was at least 300 fold more potent than the other prostanoids with a mean EC50 of 12 nM. Sulprostone caused contraction only at the highest concentration tested (30 microM). PGE2 and PGI2 caused relaxations at low concentrations, and only caused contractile responses at high concentrations (greater than or equal to 10 microM). In contrast, DME2 caused small contractions at low concentrations but relaxation at the highest concentration tested (30 microM). 3. The rank order of contractile agonist potency was: U-46619 much greater than 11 beta-PGF2 congruent to PGF2 alpha greater than PGD2 greater than PGE2 greater than PGI2 congruent to sulprostone congruent to DME2. 4. The TP-receptor blocking drug, AH23848 (1 microM) antagonized the contractile effects of U-46619, PGD2, PGF2 alpha and 11 beta-PGF2, but had no effect against contractions to carbachol. In a single experiment, a pA2 of 8.3 (slope = 1.2) was obtained for AH23848 against U-46619. 5. In most preparations, administration of AH23848 (1 microM) to human bronchus resulted in small, transient contractile responses. 6. The results obtained with both the agonists and the antagonist, AH23848 are therefore consistent with prostanoid-induced contractions of human bronchial smooth muscle being mediated by TP-receptors.


The terminal oxidase of Photobacterium phosphoreum. A novel cytochrome.
The terminal oxidase of Photobacterium phosphoreum has been purified to the electrophoretically homogeneous state and some of its properties have been studied. The enzyme catalyses oxidation of ascorbate in the presence of phenazine methosulphate or N,N,N',N'-tetramethyl-p-phenylenediamine. The reaction is inhibited by cyanide. Nitrite at comparatively high concentrations inhibits the enzyme, but the enzyme does not catalyse nitrite reduction with ascorbate plus the electron mediator as the electron donor. The enzyme shows the absorption peaks at 632, 565, 534 and 436 nm in the reduced form. It has two kinds of haems: protohaem and haem d. Namely, the enzyme is a 'cytochrome bd'-type oxidase; a novel cytochrome.


Reproductive tract development and puberty in two lines of Nellore heifers selected for postweaning weight.
The objective was to evaluate reproductive tract development (ovary and uterus) and onset of puberty in two lines of Nellore heifers (Bos indicus) selected for postweaning weight. A total of 123 heifers, including 46 from the control Nellore line (NeC) and 77 from the selection Nellore line (NeS) were used. Every 18 to 21 days from 12 to 24 months of age, average ovarian area (OVA), endometrial thickness (ETh), and diameter of the largest follicle in each ovary were evaluated (using transrectal ultrasonography), and body weight, hip height, and body condition score were measured. There were no differences between NeS and NeC heifers for ETh or OVA (P < 0.05). Genetic selection for higher postweaning weight had no negative influence on the onset of puberty, with 52% and 48% of NeC and NeS heifers, respectively, pubertal at 24 months of age (P = 0.49). Heifers that reached puberty at the end of the study were heavier (NeC, 296.9 vs. 276.7 kg; NeS, 343.5 vs. 327.9 kg; P < 0.01) and younger (NeC, 23.4 vs. 24.2 mo; NeS, 22.7 vs. 24.0 months; P < 0.01) than those that did not. Furthermore, heifers that were heavier at weaning reached puberty earlier. Pubertal heifers had a greater OVA (4.15 vs. 3.14 cm(2); P < 0.01) and ETh (12.15 vs. 9.93 mm; P < 0.01) than nonpubertal heifers. Taken together, OVA and ETh had positive effects (P < 0.01) on the onset of puberty and were suitable indicator traits of heifer sexual precocity in pasture management systems. However, selection for weight did not alter ovarian or endometrial development, or manifestation of puberty at 24 months of age. Among the growth traits studied, weaning weight and weight at puberty had significant positive effects on manifestation of first estrus.


Immunoconjugates: applications in targeted drug delivery for cancer therapy.
Monoclonal antibodies can be produced against virtually any molecule, and unlike polyclonal antisera, they are highly specific. There has been great improvement in the monoclonal antibody production technique since its inception in 1975. The idea behind using monoclonals to direct cancer treatments is based on the fact that surfaces of tumor contain a wide variety of proteins, some of which are specific to the tumor type. Monoclonal antibodies that bind to such tumor-specific antigens could be used, either alone or as conjugates of drugs and toxins (immunoconjugates), to selectively seek out and destroy these tumor cells. Targeted drug delivery therapy of tumor using monoclonals or their conjugates has been reported by many investigators, and the early results are quite promising. However, many obstacles still have to be overcome before immunoconjugates become a valuable agent in the treatment of human diseases including cancer.


Contamination of red chilli with aflatoxin b1 in pakistan.
A survey of red chilli (Capsicum indicum) for contamination with aflatoxins was performed on different samples comprising whole, crushed and powdered red chilli collected from various stores located in the city of Karachi, Pakistan. Red chilli required rather rigorous clean-up procedure for removal of adulterants and interference resulting from various types of compounds. A modified Romer method followed by bi-directional thin layer chromatography (TLC) was used for the detection of aflatoxins and confirmatory tests were performed by spraying the TLC plates with 50% sulphuric acid and making the derivative with trifluoroacetic acid. Of all the 176 samples of red chilli examined, 66% were found to be contaminated with aflatoxin B1. Generally, samples of red chilli exammined were found to be fairly low in aflatoxin B1 content, whereas only seven samples were found to contain concentrations greater than 25 μg/kg of aflatoxin B1.


Price Transparency in the Online Age.
Plastic surgeons are sometimes hesitant to provide their pricing information online, due to several concerns. However, if implemented right, price transparency can be used as a lead generation tool that provides consumers with the pricing information they want and gives the physician the consumer's contact information for follow-up. This study took place during the author's first year in private practice in a new city. An interactive price transparency platform (ie, cost estimator) was integrated into his website, allowing consumers to submit a "wishlist" of procedures to check pricing on these procedures of interest. However, the consumer must submit their contact information to receive the desired breakdown of costs that are tailored based on the author's medical fees. During that first year, without any advertising expenditure, the author's website received 412 wishlists from 208 unique consumers. Consumers (17.8%) that submitted a wishlist came in for a consultation and 62% of those booked a procedure. The average value of a booked procedure was over US $4000 and cumulatively, all of the leads from this one lead source in that first year generated over US $92,000 in revenue. When compared with non-price-aware patients, price-aware patients were 41% more likely to book a procedure. Price transparency led to greater efficiency and reduced consultations that ended in "sticker shock." When prudently integrated into a medical practice, price transparency can be a great lead generation source for patients that are (1) paying out of pocket for medically necessary services due to a high-deductible health plan or (2) paying for services not typically covered by insurance, such as cosmetic services.


[Association of nm23-H1 with orthopedic oncological conditions].
To explore the correlation between nm23-H1 gene and malignant and semi-malignant bone tumors. Thirty surgical specimens were collected, including 8 osteosarcomas, 7 giant cell tumors, 4 chondrosarcomas, 2 Ewing's sarcomas, 2 malignant fibrohistocytomas, 1 neurofibrosarcoma, 1 schwannoma, and 5 metastatic cancers. The expression of nm23-H1 in these specimens was observed by in situ hybridization and immunohistochemical staining. The expression of nm23-H1 in 4 cases of primary giant cell tumor (GCT) was high, but was low or absent in 3 recurrent ones. In 4 cases of chondrosarcomas, the expression was positive. Its expression was basically negative in Ewing's tumor, malignant fibrous histiocytoma and metastatic sarcomas. There is no association of nm23-H1 with osteosarcoma.


PARK16 polymorphisms, interaction with smoking, and sporadic Parkinson's disease in Japan.
Epidemiological evidence on the relationships between PARK16 single nucleotide polymorphisms (SNPs) and Parkinson's disease (PD) is inconsistent. We examined this issue in Japan. Included were 229 cases within six years of PD onset. Controls were 356 patients without neurodegenerative disease. Compared with subjects with the AA genotype of SNP rs823128, those with the AG genotype, but not the GG genotype, had a significantly reduced risk of sporadic PD. Compared with the AA genotype of SNP rs947211, both the AG genotype and the GG genotype were significantly related to an increased risk of sporadic PD. Using subjects with the AA genotype of SNP rs823156 as a reference group, there were significant inverse relationships under the additive and dominant models. No significant relationships were found between SNPs rs16856139 or rs11240572 and sporadic PD. The CAAAC, the TGAGA, and the CAGAC haplotypes were significantly related to sporadic PD. The additive interaction between SNP rs823128 and smoking affecting sporadic PD was significant, although the multiplicative interaction was not significant. The PARK16 SNPs rs823128, rs947211, and rs823156 and the CAAAC, TGAGA, and CAGAC haplotypes may be significantly associated with sporadic PD in Japan. New evidence of an additive interaction between SNP rs823156 and smoking is suggested.


Left ventricular torsion abnormalities in patients with obstructive sleep apnea syndrome: an early sign of subclinical dysfunction.
Previous echocardiographic studies using tissue Doppler imaging (TDI) and speckle tracking imaging (STI) have demonstrated that obstructive sleep apnea syndrome (OSAS) patients may develop subclinical left ventricular (LV) systolic and diastolic dysfunction. Our purpose was to evaluate the impact of OSAS on LV torsion dynamics and aortic stiffness by using TDI and STI echocardiography. Forty-two patients with OSAS and no comorbidities were studied. They were classified into mild and severe OSAS according to the apnea-hypopnea index (AHI). Thirty-five healthy subjects were selected as controls. Fifteen patients with severe OSAS underwent chronic nocturnal nasal continuous positive airway pressure (CPAP) therapy. Standard echocardiographic parameters were assessed. Global LV longitudinal strain (LS), radial and circumferential strain were determined by STI. Averaged LV rotation and rotational velocities from the base and apex were obtained and used for calculation of LV torsion (LVtor). Mitral annular velocities and aortic wall velocities and strain (AoS) were also obtained by TDI. Severe OSAS had decreased LS compared with control subjects. LVtor increased significantly in severe OSAS compared to normals (p<.001) as a result of a predominant increase in apical rotation and was independently related to AHI and AoS in a multiple stepwise linear regression model. The group treated with CPAP had a significant decrease in LVtor and aortic stiffness index and significant increase in LS and AoS. LVtor, LS and AoS were identified as parameters demonstrating an association between LV dysfunction, aortic stiffness and severity of OSAS independently of other possible factors or comorbidities.


Ratcheting-fatigue behavior of trabecular bone under cyclic tensile-compressive loading.
This study aims to investigate the ratcheting-fatigue behaviors of trabecular bone under cyclic tension-compression, which are produced due to the accumulations of residual strain in trabecular bone. Simultaneously, the effects of different loading conditions on ratcheting behaviors of trabecular bone were probed. It is found that the gap between ratcheting strains under three stress amplitudes will gradually widen. As the stress amplitude increases, the ratcheting strain also increases. Mean stress has a significant effect on the ratcheting strain. When the mean stress is 0 MPa and 0.155 MPa, the ratcheting strain increases with the number of cycles. However, when the mean stress is -0.155 MPa, the ratcheting strain decreases as the cycle goes on. The existence of double stress peak holding time causes the creep deformation of trabecular bone, which leads to the increase of ratcheting strain. It is also noted that the ratcheting strain is greatly increased with prolongation of stress peak holding time. The digital image correlation (DIC) technique was applied to analyze the fatigue failure of trabecular bone under cyclic tension-compression. It is found that the increase of stress amplitude accelerates the damage of sample and further reduces its fatigue life. Cracks are observed in trabecular bone sample, and it is noted that the crack propagation is rapid during cyclic loading.


Motor-skill learning in a novel running-wheel task is dependent on D1 dopamine receptors in the striatum.
Evidence indicates that dopamine receptors regulate processes of procedural learning in the sensorimotor striatum. Our previous studies revealed that the indirect dopamine receptor agonist cocaine alters motor-skill learning-associated gene regulation in the sensorimotor striatum. Cocaine-induced gene regulation in the striatum is principally mediated by D1 dopamine receptors. We investigated the effects of cocaine and striatal D1 receptor antagonism on motor-skill learning. Rats were trained on a running wheel (40-60 min, 2-5 days) to learn a new motor skill, that is, the ability to control the movement of the wheel. Immediately before each training session, the animals received an injection of vehicle or cocaine (25 mg/kg, i.p.), and/or the D1 receptor antagonist SCH-23390 (0, 3, 10 microg/kg, i.p., or 0, 0.3, 1 microg, intrastriatal via chronically implanted cannula). The animal's ability to control/balance the moving wheel (wheel skill) was tested before and repeatedly after the training. Normal wheel-skill memory lasted for at least 4 weeks. Cocaine administered before the training tended to attenuate skill learning. Systemic administration of SCH-23390 alone also impaired skill learning. However, cocaine given in conjunction with the lower SCH-23390 dose (3 microg/kg) reversed the inhibition of skill learning produced by the D1 receptor antagonist, enabling intact skill performance during the whole post-training period. In contrast, when cocaine was administered with the higher SCH-23390 dose (10 microg/kg), skill performance was normalized 1-6 days after the training, but these rats lost their improved wheel skill by day 18 after the training. Similar effects were produced by SCH-23390 (0.3-1 microg) infused into the striatum. Our results indicate that cocaine interferes with normal motor-skill learning, which seems to be dependent on optimal D1 receptor signaling. Furthermore, our findings demonstrate that D1 receptors in the striatum are critical for consolidation of long-term skill memory.


Percutaneous ureteral fulguration: a nonsurgical technique for ureteral occlusion.
Three patients with lower urinary tract fistulas after multiple operations and radiation therapy for pelvic cancer were treated with percutaneous ureteral fulguration and nephrostomy tube drainage. This technique occluded the ureter and allowed for maintenance of a dry fistula site in all 3 patients. There were no complications. The longest followup in these patients was 21 months. The procedure is simple technically and it can be performed with the patient under local anesthesia. The technique of percutaneous ureteral fulguration is described and other techniques for nonoperative occlusion of the ureter are discussed.


Emergence of nalidixic acid resistant Shigella dysenteriae type 1 in Thailand: an outbreak associated with consumption of a coconut milk dessert.
Although Shigella dysenteriae type 1 has been responsible for large outbreaks of severe dysentery in many parts of Asia, relatively few cases of this disease have been reported from Thailand and have generally not involved nalidixic acid resistant strains. Beginning March 1991, all patients with diarrhoea seen at the hospital outpatient department (OPD) in Suan Phung, Thailand (a western district near the Burmese border) were cultured for enteric pathogens. Shigella dysenteriae 1 was first recognized in July 1992, and an OPD-based case-control study was conducted to pinpoint the source of the outbreak in the community. For each case of culture confirmed S. dysenteriae 1, one control person without diarrhoea, matched by age and date of visit, was randomly selected from the OPD registry. Of 197 patients treated for diarrhoea at the hospital OPD in July and August 1992, 79 (40%) had bloody diarrhoea, compared with 86/561 (15%) patients seen during 16 months of previous surveillance (P < 0.0001). Shigella dysenteriae 1 was isolated from 33/197 (17%) patients. Compared to matched controls, patients with S. dysenteriae 1 were more likely to attend one of the local elementary schools (odds ratio = 6.74, P = 0.025), or live in the community surrounding this school (odds ratio for non-school age people = 18.0, P = 0.008). A cross-sectional study conducted at the school indicated that 50 (10%) of 485 students had dysentery in July. A coconut milk dessert prepared at the school was identified as the vehicle of transmission (relative risk = 24.9, P < 0.0001). Nalidixic acid resistant S. dysenteriae 1 emerged in a community in Thailand, and was traced to a point source outbreak at a local school.


Structural homology of Torpedo californica acetylcholine receptor subunits.
The nicotinic acetylcholine receptor (AChR) from the electroplax of the ray Torpedo californica is composed of five subunits present in a molar stoichiometry of alpha 2 beta gamma delta (refs 1-3) and contains both the binding site for the neurotransmitter and the cation gating unit (reviewed in refs 4-6). We have recently elucidated the complete primary structures of the alpha-, beta- and delta-subunit precursors of the T. californica AChR by cloning and sequencing cDNAs for these polypeptides. Here, we report the whole primary structure of the gamma-subunit precursor of the AChR deduced from the nucleotide sequence of the cloned cDNA. Comparison of the amino acid sequences of the four subunits reveals marked homology among them. The close resemblance among the hydrophilicity profiles and predicted secondary structures of all the subunits suggests that these polypeptides are oriented in a pseudosymmetric fashion across the membrane. Each subunit contains four putative transmembrane segments that may be involved in the ionic channel. The transmembrane topology of the subunit molecules has also been inferred.


Building knowledge about health services utilization by refugees.
The objective of this study was to compare the utilization of outpatient physician, emergency department and hospital services between refugees and the general population in Calgary, Alberta. Data was collected on 2,280 refugees from a refugee clinic in Calgary and matched with 9,120 non-refugees. Both groups were linked to Alberta Health and Wellness administrative data to assess health services utilization over 2 years. After adjusting for age, sex and medical conditions, refugees utilized general practitioners, emergency departments and hospitals more than non-refugees. A similar proportion in the two groups had seen a general practitioner within 1 week prior to their emergency department visit; however, refugees were more likely to have been triaged for urgent conditions and female refugees seen for pregnancy-related conditions than non-refugees. Refugees were more likely to have had infectious and parasitic diseases. Refugees utilized health services more than non-refugees with no evidence of underutilization.


Total hip arthroplasty using highly cross-linked polyethylene in patients younger than 50 years with minimum 10-year follow-up.
The purpose of this study was to investigate the relatively long-term outcomes in 50 patients (54 hips) younger than 50 years of age who underwent total hip arthroplasty using highly cross-linked polyethylene (HXLPE) liners. With a minimum follow-up of 10 years, mean age at time of surgery was 38.9 years (range, 15-50 years). Survivorship was 100%. There was no radiographic evidence of osteolysis or component loosening. Mean steady-state femoral head penetration rate was 0.020 ± 0.0047 mm/yr. Clinical outcomes were excellent, with mean Harris hip score of 91.2 (range, 72-99) points at final follow-up.


Cloning, expression, and characterization of a thermostable GH7 endoglucanase from Myceliophthora thermophila capable of high-consistency enzymatic liquefaction.
An endoglucanase gene from the thermophilic fungus Myceliophthora thermophila, belonging to the glycoside hydrolase family 7, was functionally expressed in methylotrophic yeast Pichia pastoris. The putative endoglucanase from the genomic DNA was successfully cloned in P. pastoris X-33 and the recombinant enzyme was purified to its homogeneity (65 kDa) and subsequently characterized. Substrate specificity analysis revealed that the enzyme exhibits high activity on substrates containing β-1,4-glycosidic bonds such as carboxymethyl cellulose, barley β-glucan, and cello-oligosaccharides, as well as activity on xylan-containing substrates, including arabinoxylan and oat spelt xylan. MtEG7a was proved to liquefy rapidly and efficiently pretreated wheat straw, indicating its key role to the initial step of hydrolysis of high-solids lignocellulose substrates. High thermostability of the endoglucanase reflects potential commercial significance of the enzyme.


Smartphone apps for orthopaedic sports medicine - a smart move?
With the advent of smartphones together with their downloadable applications (apps), there is increasing opportunities for doctors, including orthopaedic sports surgeons, to integrate such technology into clinical practice. However, the clinical reliability of these medical apps remains questionable. We reviewed available apps themed specifically towards Orthopaedic Sports Medicine and related conditions and assessed the level of medical professional involvement in their design and content, along with a review of these apps. The most popular smartphone app stores (Android, Apple, Blackberry, Windows, Samsung, Nokia) were searched for Orthopaedic Sports medicine themed apps, using the search terms; Orthopaedic Sports Medicine, Orthopaedics, Sports medicine, Knee Injury, Shoulder Injury, Anterior Cruciate Ligament Tear, Medial Collateral Ligament Tear, Rotator Cuff Tear, Meniscal Tear, Tennis Elbow. All English language apps related to orthopaedic sports medicine were included. A total of 76 individual Orthopaedic Sports Medicine themed apps were identified. According to app store classifications, there were 45 (59 %) medical themed apps, 28 (37 %) health and fitness themed apps, 1 (1 %) business app, 1 (1 %) reference app and 1 (1 %) sports app. Forty-nine (64 %) apps were available for download free of charge. For those that charged access, the prices ranged from £0.69 to £69.99. Only 51 % of sports medicine apps had customer satisfaction ratings and 39 % had named medical professional involvement in their development or content. We found the majority of Orthopaedic Sports Medicine apps had no named medical professional involvement, raising concerns over their content and evidence-base. We recommend increased regulation of such apps to improve the accountability of app content.


Redundant food searches by capuchin monkeys (Cebus apella): a failure of metacognition?
This study investigated capuchin monkeys' understanding of their own visual search behavior as a means to gather information. Five monkeys were presented with three tubes that could be visually searched to determine the location of a bait. The bait's visibility was experimentally manipulated, and the monkeys' spontaneous visual searches before tube selection were analyzed. In Experiment 1, three monkeys selected the baited tube significantly above chance; however, the monkeys also searched transparent tubes. In Experiment 2, a bent tube in which food was never visible was introduced. When the bent tube was baited, the monkeys failed to deduce the bait location and responded randomly. They also continued to look into the bent tube despite not gaining any pertinent information from it. The capuchin monkeys' behavior contrasts with the efficient employment of visual search behavior reported in humans, apes and macaques. This difference is consistent with species-related variations in metacognitive abilities, although other explanations are also possible.


Indigenous communities and influenza: protocol for a systematic review and meta-analysis.
Several studies have documented that specific Indigenous groups have been disproportionately affected by previous pandemics. The objective of this paper is to describe the protocol to be used in a review and meta-analysis of the literature on Indigenous groups and influenza. Using this protocol as a guide, a future study will provide a comprehensive historical overview of pre-COVID impact of influenza on Indigenous groups by combining data from the last five influenza pandemics and seasonal influenza up to date. The review will include peer-reviewed original studies published in English, Spanish, Portuguese, Swedish, Danish, and Norwegian. Records will be identified through systematic literature search in eight databases: Embase, MEDLINE, CINAHL, Web of Science, Academic Search Ultimate, SocINDEX, ASSIA, and Google Scholar. Results will be summarized narratively and using meta-analytic strategies. To our knowledge, there is no systematic review combining historical data on the impact of both seasonal and pandemic influenza on Indigenous populations. By summarizing results within and across Indigenous groups, different countries, and historical periods, as well as research in six different languages, we aim to provide information on how strong the risk for influenza is among Indigenous groups and how consistent this risk is across groups, regions, time, and seasonal versus the specific pandemic influenza strains. PROSPERO CRD42021246391.


The relative cytotoxicity of personal care preservative systems in Balb/C 3T3 clone A31 embryonic mouse cells and the effect of selected preservative systems upon the toxicity of a standard rinse-off formulation.
Biocide chemicals are commonly used as preservatives for cosmetic and personal care products and the conditions for their use are stipulated in Annex VI of the Cosmetics Directive. In these studies the cytotoxicity (EC50 and EC90) of a range of preservatives including the isothiazolinone family, formaldehyde donors, parabens mixtures and organic acids have been established in the Balb/C 3T3 clone A31 fibroblast cell-line following a 1h exposure. Cell viability was established using the neutral red uptake assay 24h after exposure. The potency of the preservatives spanned several orders of magnitude from the isothiazolinones (EC50<10ppm) to the organic acids (EC50>10,000ppm). Although these values are directly proportional to the anti-microbial efficacy of the actives, they do not reflect the addition levels commonly used to preserve formulations, which are intended to provide prolonged protection against a wide spectrum of spoilage organisms. In a further study, the cytotoxic profile of an unpreserved standard rinse-off body wash formulation was assessed. Two concentrations of the formulation were selected: 0.1% v/v (EC98) and 0.15% v/v (EC82) to study the effects of selected preservative chemicals at recommended addition levels upon the cytotoxicity of the formulation. At 0.1%, only preservation with benzoate/sorbate at the highest addition level increased the toxicity, whereas at 0.15%, preservation with 2-bromo-2-nitro-propane-1,3-diol increased the cytotoxicity of the formulation. No other preservatives, including isothiazolinones and formaldehyde donors affected the basal cytotoxicity of the formulation. Theses studies have provided a standardised assessment of the cytotoxicity of cosmetic preservatives and demonstrated that preservation of a rinse-off formulation at recommended addition levels is unlikely to affect the cytotoxic profile.


Heavy metal concentration profiles and pollution assessment in the Jiangsu offshore area, China.
The concentration profiles of various major and trace heavy metals (Cu, Pb, Zn, Cr, Cd, As, Hg, Ni, Li, and Co) were investigated along a 40.1-m-long sediment core in the offshore Jiangsu area of China, to assess their depositional trends and contamination levels. All metals, except Cd, exhibited similar profiles with high average concentrations during the Marine Isotope Stage 2-4 period. The sediment trace-metal concentrations were primarily related to grain size and sediment sources, with almost all heavy metals (except Cd) being positively correlated. Enrichment factors, geoaccumulation indices, and principal component analysis indicated no elemental enrichment or contamination. The high EF and Igeo values of As, Hg, and Li may be related to their background values.


Comparative measurement of thromboxane A2 metabolites in exhaled breath condensate by different immunoassays.
Differences between detection techniques may be partly responsible for variable mediator concentrations reported in exhaled breath condensate (EBC). We compared two types of immunoassays to estimate thromboxane A(2) (TxA(2)) concentration. Thromboxane B(2) (TxB(2)) levels were measured by enzyme immunoassay (EIA) and TxB(2)/2,3-dinor TxB(2) by radioimmunoassay (RIA) in 10 healthy subjects and 13 asthmatic patients. 2,3-Dinor TxB(2) was also determined by a separate EIA. Thromboxane was detected in all samples by RIA, but only in about 75% of samples by EIA. 2,3-Dinor TxB(2) was detected in most samples. There was no agreement between the results of the different immunoassays. As compared to healthy subjects, exhaled breath condensates of asthmatic patients contained significantly more immunoreactivity by RIA and TxB(2) EIA (but not by 2,3-dinor TxB(2) EIA). RIA and EIA resulted in vastly different absolute values. The difference found between healthy volunteers and asthmatic patients however, suggests an increased level of TxA(2) in the airways of asthmatics.


Estrogen receptor β activation ameliorates DSS-induced chronic colitis by inhibiting inflammation and promoting Treg differentiation.
Estrogen receptor (ER) β activation has anti-inflammatory activity. However, its effect on the development of inflammatory bowel disease (IBD) and the underlying mechanism have not been clarified. This study aimed to assess the clinical value of ERβ+CD4+ T cells in IBD patients and examine the anti-inflammatory role of ERβ activation in dextran sulfate sodium (DSS)-induced chronic colitis in mice. We investigated the effects of ERB041 (an ERβ-specific agonist) on inflammatory cytokines and pro-inflammatory T-cell and regulatory T-cell (Treg) responses in murine colitis. We tested the role of ERβ activation on Treg differentiation and its activity to suppress T-cell proliferation in vitro. We found that reduced frequency of circulating ERβ+CD4+ T cells in IBD patients was negatively correlated with inflammation and disease severity. ERβ and FoxP3 expression co-localized in the intestinal tissues of IBD patients. Treatment with ERB041 significantly mitigated colitis-induced weight loss, inflammation, and disease severity. It also restored the ERβ+CD4+ T cell population in the spleen and colon lamina propria of these mice. ERB041 treatment inhibited CD4+CD25- and CD8+ T cell infiltration and restored Tregs and activated T-cell immunoreceptor with Ig and ITIM domains (TIGIT)+ Tregs in the colon lamina propria. In vitro, we found that ERβ activation enhanced Treg differentiation, immunosuppression, and TGF-β1/Smad signaling in CD4+ T cells. Our data suggest that ERβ+CD4+ T cells represent a potential biomarker for evaluating IBD disease severity, and ERβ activation may be valuable for the treatment of IBD by enhancing the Treg response.


A simple kinetic spectrophotometric method for the determination of oxamniquine in formulations and spiked biological fluids.
A simple and sensitive kinetic method for the determination of oxamniquine in pharmaceutical preparations and biological fluids was developed. The procedure is based upon a kinetic investigation of the oxidation reaction of the drug with alkaline potassium permanganate at room temperature for a fixed time of 20 min. The absorbance of the colored manganate ions was measured at 610 nm. Alternatively, the decrease in the absorbance of potassium permanganate after addition of the drug was measured at 525 nm. The absorbance concentration plots in both procedures were rectilinear over the range 0.5-4 microg ml(-1). The concentration of oxamniquine is calculated using the corresponding calibration equation for the fixed-time method. The determination of oxamniquine by fixed-concentration and rate-constant methods was feasible with the calibration equations obtained but the fixed time method had been found to be more applicable. Both procedures were applied to the determination of oxamniquine in formulations. The results obtained were in good agreement with those obtained using the official method. The fixed time method of 20 min was further applied to spiked human urine and plasma, the recoveries (%) were 100.94 +/- 0.57 and 98.07 +/- 0.88 for urine and plasma, respectively, at 610 nm, and 97.51 +/- 1.27 and 95.69 +/- 1.23 for urine and plasma, respectively, at 525 nm.


Training, attitudes and practice of district health workers in Kenya.
The 1994 mental health policy in Kenya was rooted in the concepts of Primary Health Care articulated at Alma Ata, and required that mental health care be decentralized to all levels of the health care system, and delivered by all cadres of health staff rather than just mental health specialists. However, effective implementation of this policy was likely to be influenced by the degree to which the training, attitudes and practice of health staff was consistent with and supportive of the mental health policy. This article therefore reports a study conducted in 1997, which examined the training, attitudes and practice of district level health staff in relation to mental health care and compared them with the national mental health policy of 1994. A semi-structured questionnaire was sent to the medical superintendents of all district hospitals in Kenya, for distribution to respondents from each cadre of health staff. A total of 148 health workers from 28 districts out of 44 eligible districts (63%) responded. District health workers did not think general health workers ought to manage most psychiatric patients, even if they were capable of doing so, preferring a system where these patients were managed by specialists and were not admitted into general wards. They also tended to equate mental illness with psychosis. Despite their training in mental health care and their theoretical knowledge of the principles of Primary Health Care, the attitude and mental health care practice of most health workers were in keeping with a more medical model of health care, emphasising pharmacological treatment and expecting psychiatric patients to conform to the standard Sick Role. This orientation, being at variance with the orientation of the 1994 mental health policy, may have contributed to difficulties in implementation of the policy.


Surgery after embolization of cerebral arterio-venous malformation: experience of 123 cases.
A group of 123 patients with large or critically located arterio-venous malformations (AVMs), operated on between 1990 and 2011 and who underwent preoperative embolization, was assessed in order to clarify the risks of this combined treatment. AVM location, volume, and Spetzler's grade were assessed in each case; AVM volume was over 20 cm(3) in 49 % of the cases; Spetzler's grade was 3 or above in 76 % of the cases (with 34 cases in grades 4-5). A mean of 2.3 embolization procedures per patient were carried out, using bucrylate and, more recently, Onyx and/or Glubran; a 4.5 % procedure-related complication rate was observed. Complications occurring after surgery were classified as hemorrhagic (16 cases, 8 requiring surgical evacuation) or ischemic (4 cases); hemorrhagic complications were more common for AVMs with volumes >20 cm(3) and/or deep feeders. Surgery-related unfavorable results (modified Rankin Score > 2) were observed in 6 % of patients in Spetzler's grade 3, and in 20-25 % of patients in grades 4-5. More recently, a triple treatment (radiosurgery + embolization + surgery) allowed for obtaining favorable results (mRS 0-2) in all patients. It has been concluded that a combined treatment with embolization and surgery constitutes a reasonable choice for complex cerebral AVMs; the association of radiosurgery may improve the patients outcome.


Self-assembled fisetin-phospholipid complex: Fisetin-integrated phytosomes for effective delivery to breast cancer.
Nowadays, fisetin (FIS) is extensively studied as potent anticancer surrogate with a multitarget actions against various types of cancers including breast cancer. However, its poor aqueous solubility handicapped its clinical utility. The current work endeavored, for the first time, to develop FIS phytosomes (FIS-PHY) for improving its physicochemical properties and subsequently its anticancer activity. Optimization of FIS- phytosomes involved different preparation techniques (Thin film hydration and ethanol injection) and different FIS: phospholipid molar ratios (1:1, 1:2, and 1:3). Complex formation was confirmed by complexation efficiency, infrared spectroscopy (IR), solubility studies and transmission electron microscope. The optimized FIS-PHY of 1:1 M ratio (PHY1) exhibited a nanometric particle size of 233.01 ± 9.46 nm with homogenous distribution (PDI = 0.27), negative zeta potential of - 29.41 mV, 100% complexation efficiency and controlled drug release over 24 h. In-vitro cytotoxicity study showed 2.5-fold decrease in IC50 of PHY1 compared with free FIS. Also, pharmacodynamic studies confirmed the promoted cytotoxicity of PHY1 against breast cancer through modulating TGF-β1/MMP-9 molecular pathways of tumorigenesis. Overall, overcoming FIS drawbacks were successfully achieved through development of innovative biocompatible phytosomal system.


An outbreak of Halomonas phocaeensis sp. nov. bacteraemia in a neonatal intensive care unit.
Unidentified Gram-negative aerobic rods were recovered from the blood cultures of six neonates in a neonatal intensive care facility in Tunis, Tunisia. 16S rRNA gene sequencing showed that these were members of the Halomonas genus, with <97% sequence similarity to their closest relative. The observation of unique phenotypic characteristics of these organisms supported a novel species and the name Halomonas phocaeensis sp. nov. was proposed. A case-control study and conditional logistic regression analysis suggested that the administration of fresh frozen plasma was the only independent risk factor for developing H. phocaeensis bacteraemia. Observational studies indicated that fresh frozen plasma was warmed up using a water-bath. This first description of a nosocomial outbreak of H. phocaeensis bacteraemia illustrates the infection risks associated with poorly controlled water hygiene in healthcare settings.


Post-Shock Asystole in Patients Dying Out of Hospital While Wearing a Cardioverter Defibrillator.
The wearable cardioverter-defibrillator (WCD) prevents sudden cardiac death due to ventricular tachycardia (VT) or ventricular fibrillation (VF) but does not pace for post-shock asystole (PS-A) or bradycardia (PS-B;<50 beats/ min). The purpose of this study was to assess PS-A and PS-B in patients dying out of hospital (OOH) while wearing a WCD. The database of the U.S. Food and Drug Administration Manufacturers and User Facility Device Experience (MAUDE) was queried for manufacturers' reports of OOH deaths while patients were wearing a WCD. Excluded were patients who did not receive a shock or were initially shocked for asystole or during resuscitation. From January 2017 to March 2022, 313 patients received an initial WCD shock for VF (n = 150), VT (n = 90), and non-VF/VT rhythms (n = 73). PS-A occurred in 204 patients (65.2%), and PS-B occurred in 111 (35.5%); 85 (41.7%) PS-A patients also had PS-B. Most PS-A patients (n = 185; 90.7%) had an initial shocked rhythm of VF or VT, but 19 patients (9.3%) were initially inappropriately shocked for atrial fibrillation/supraventricular tachycardia (n = 7) and idioventricular (n = 8) or sinus (n = 4) rhythm. PS-A occurred after the first WCD shock in 118 (63.8%) and after the first, second, or third shocks in 159 patients (85.9%). Seven patients had post-shock heart block. Eight patients had permanent pacemakers; 1 became nonfunctional after 1 shock, and 7 showed noncapture and/or asystole after 1 to 4 shocks. Post-shock asystole appears to be common in patients who die OOH after being shocked by a WCD for VF or VT. PS-A also occurs after inappropriate WCD shocks for non-VF/VT rhythms. Implanted pacemakers may not prevent PS-A after a WCD shock. WCD backup pacing should be explored.


Dissolution medium responsive simvastatin release from biodegradable apatite cements and the therapeutic effect in osteoporosis rats.
Bio-convertible artificial bone with slow release of anti-osteoporosis drug is useful to treat osteoporosis. Apatite cement containing 6% simvastatin (APD) had lower crystallinity than natural bone. In-vitro drug release tests in simulated body fluid (pH 7.8) and acetate buffer (pH 4.5) were performed at 37.0 C as physical models of osteoblast and osteoclast conditions (SOB and SOC). The device had lower drug release rate under SOB, but significantly higher rates under SOC. The simvastatin release rate changed depending on dissolution media, it repeated twice, and the rate under SOC was 15 times higher than under SOB. The device showed dissolution medium responsive drug release. After implantation of the APD in osteoporosis rats, the bone mineral density was evaluated by the x-ray computed tomography. The result indicated that the bone mineral density of APD implanted rat was significantly higher than that of control diseased. The result indicated that the device was therapeutically useful to bone regeneration.


"Growing pains" in childhood--a proposal for treatment.
"Growing pains" is a benign clinical entity of unknown etiology. This study examines a muscle stretching treatment based on a theory that the etiology of these pains is related to fatigue. The experimental group (18 children) showed a more rapid resolution of their symptoms over an 18 month period when compared to the control group (16 children).


EVALUATION OF RETINAL DISPLACEMENT FOLLOWING PRIMARY SCLERAL BUCKLING FOR MACULA-INVOLVING RHEGMATOGENOUS RETINAL DETACHMENT.
To evaluate the incidence and degree of retinal displacement following scleral buckling surgery for macula-involving rhegmatogenous retinal detachment. Retrospective interventional case series comprised of patients treated with primary scleral buckling procedure without gas tamponade for macula-involving rhegmatogenous retinal detachment and imaged postoperatively with fundus autofluorescence imaging between June 1, 2016 and July 25, 2021. Clinical notes, operative reports, fundus autofluorescence photographs, and optical coherence tomography images were reviewed. The presence and degree of retinal displacement were recorded. Twelve eyes of 11 patients were included. One (8%) eye with an epiretinal membrane demonstrated 0.1 mm of retinal displacement along the superior arcade and in the superotemporal periphery. The remainder of eyes (92%) did not show any identifiable signs of retinal displacement. Retinal displacement does not seem to be a frequent complication of primary scleral buckling surgery for macula-involving rhegmatogenous retinal detachment.


Increased CD133 expression in bone marrow of myelodysplastic syndromes.
Fresh frozen bone marrow biopsies were evaluated immunohistochemically, applying monoclonal antibodies against CD31, CD34, VEGFR-2 and CD133, a novel marker identifying human endothelial progenitor cells (EPCs). Specimens of 51 patients diagnosed with MDS were compared with 16 AML and 18 controls. The percentage of CD34 expressing cells was increased and CD31 expression was decreased in advanced stages of MDS compared with normal BM. VEGFR-2 expression was also raised in MDS. Here we show for the first time that increased numbers of CD133 positive cells are present in the majority of MDS patients. Additionally, those cells occasionally seem to contribute to capillary forming units in bone marrow.


Ambroxol alleviates hepatic ischemia reperfusion injury by antioxidant and antiapoptotic pathways.
Hepatic ischemia/reperfusion (HI/R) injury is a common pathologic process caused by many clinical settings, such as liver resection, liver transplantation, hypovolemic shock, and trauma. The use of ambroxol, which acts as a mucolytic agent, provides antioxidant and anti-inflammatory effects. A rat model of HI/R was induced by clamping the hepatic artery, the hepatoportal vein, and the bile duct with a vascular clamp for 30 minutes followed by reperfusion for 6 hours under anesthesia. The sham group underwent laparotomy without hepatic ischemia. The ambroxol group was injected into the tail vein in the ambroxol group 5 minutes before HI/R at one dose of 20 mg/kg, 80 mg/kg, or 140 mg/kg. The control group underwent the same procedure as the ambroxol group but with administration of physiological saline. Liver injury was evaluated by biochemical and histopathological examinations. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed in serum samples. Superoxide dismutase (SOD), catalase (CAT), malondiadehyde (MDA), and glutathione (GSH) were spectrophotometrically measured. Furthermore, caspase-3, Bcl-2 and Bax expression as well as the level of c-Jun N-terminal kinases (JNK) we estimated activation. Wistar rats that received 20, 80 mg or 140 mg of ambroxol displayed reduced HI/R injury compared with controls. Use of ambroxol reduced the histologic injury and significantly decreased serum ALT and AST levels. In addition, ambroxol enhanced the activity of hepatic tissue SOD and CAT, increasing GSH but decreasing MDA tissue contents. In the ambroxol group, Bcl-2 expression was increased and Bax and caspase-3 decreased compared with the controls. Furthermore, ambroxol reduced levels of phosphorylated JNK (P < .05). These results indicated that ambroxol attenuated rat HI/R through upregulation of intracellular antioxidant and anti-apoptotic signaling pathways.


Correction to: Unequivocal imaging of aluminium in human cells and tissues by an improved method using morin.
After publication of our article, it has come to our attention that our Conflict of Interest statement should read.


[Penetration of external thermal perturbations into homeothermic organisms, part I (author's transl)].
The general importance of the mean surface curvature for heat conduction problems is explained and a special symmetry with constant mean curvature on the isothermal surfaces is defined. The applicability for the body shapes of homeothermic organisms is demonstrated and the partial differential equation of heat conduction for this case is derived. The definition: heat release = real heat production + convective pseudoproduction eliminates the term of convective heat transfer through the blood stream and allows the reduction to a mere heat conduction problem. Formulas for the heat loss to the environment and for steady state temperature profiles are given. In case of sudden change of heat loss the partial differential equation is solved and a formula is derived, using dimensionless coordinates of time and distance. The mean surface curvature has strongest influence to the interior temperature field. The solution shows clearly the importance of thermal inertia of the homeothermic organism, for the external temperature wave penetrates into the body with a long phase displacement in time.


Cerebrospinal Analysis in Patients With COVID-19.
Assessment of the impact of cerebrospinal fluid (CSF) analysis including investigation for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for the optimization of patient care. In this case series, we review patients diagnosed with SARS-CoV-2 undergoing lumbar puncture (LP) admitted to Columbia University Irving Medical Center (New York, NY, USA) from March 1 to May 26, 2020. In a subset of patients, CSF SARS-CoV-2 quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) testing is performed. The average age of 27 patients who underwent LP with definitive SARS-CoV-2 (SD) was 37.5 (28.7) years. CSF profiles showed elevated white blood cell counts and protein in 44% and 52% of patients, respectively. LP results impacted treatment decisions in 10 (37%) patients, either by change of antibiotics, influence in disposition decision, or by providing an alternative diagnosis. CSF SARS-CoV-2 qRT-PCR was performed on 8 (30%) patients, with negative results in all samples. Among patients diagnosed with SARS-CoV-2, CSF results changed treatment decisions or disposition in over one-third of our patient cohort. CSF was frequently abnormal, though CSF SARS-CoV-2 qRT-PCR was negative in all samples. Further studies are required to define whether CSF SARS-CoV-2 testing is warranted in certain clinical contexts.


A new serovar of Bacillus thuringiensis possessing 28a28c flagellar antigenic structure: Bacillus thuringiensis serovar jegathesan, selectively toxic against mosquito larvae.
A novel Bacillus thuringiensis strain highly toxic to mosquitoes was isolated from soil samples in Malaysia. This strain was shown to display a new subfraction of the H-28 flagellar antigen determining a new serovar H28a28c, which was designated serovar jegathesan. Bioassays indicated that Culex quinquefasciatus larvae are the most susceptible to this new isolate, whereas toxicity to Anopheles maculatus and Aedes aegypti larvae was 10 times lower. The potency of this new serotype is also comparable to most of the Malaysian B. thuringiensis H-14 isolates.


Platinum-DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy.
Clinical studies performed by several groups suggest that platinum-DNA adduct--measured in malignant or non-malignant cells from cancer patients--may be an important marker for clinical biological effect of platinum-based chemotherapy. DNA repair is clearly an important effector of resistance to platinum-based DNA-damaging agents in tissue culture, although its role in effecting clinical resistance to these agents is not completely clear. In recent years, it has become apparent that DNA repair is an extremely complex process. Processes within DNA repair that may contribute to one or more drug resistance phenotypes include 0-6-alkytransferase activity, base excision repair, mismatch repair, nucleotide excision repair (NER), and gene specific repair. Clearly, several of these processes may concurrently show increased activity within any single cell, or tumor, at any one time. For platinum compounds, in vitro data clearly show that NER is the DNA repair pathway responsible for the repair of cisplatin-DNA damage. One critical gene within NER is ERCC1. Data exist in human ovarian cancer and in human gastric cancer that ERCC1 may be a useful marker for clinical drug resistance when platinum-based systemic chemotherapy is utilized. Although the data suggest that the relative ERCC1 mRNA level may be a good marker for NER activity in human ovarian cancer, it is unclear whether expression of this gene has any relationship to other pathways of DNA repair.


Separation of pyridinecarboxylic acid isomers and related compounds by capillary zone electrophoresis. Effect of cetyltrimethylammonium bromide on electroosmotic flow and resolution.
The effect of the addition of cetyltrimethylammonium bromide (CTAB) to the buffer system in capillary electrophoresis on electroosmotic flow (EOF) is examined. At a CTAB concentration of 2.5 x 10(-4) M, EOF is anodal (flow towards the positive detector column end). With bare silica columns, anodal EOF first increases with increasing pH, up to a maximum in the pH range 4-6 depending on CTAB concentration, then decreases as pH is further increased. Optimum resolution of pyridinecarboxylic acid isomers is obtained at pH 2.7 with a 10 mM phosphate buffer and 30 mM CTAB. Using the same buffer system, optimum resolution for hydroxy-substituted pyridinecarboxylic acid isomers is obtained at pH 7.5. The use of CTAB results in a dramatic improvement in peak shape. Preliminary results, using an excimer laser operated at 248 nm, show that the fluorescence intensity of isonicotinic acid is substantially enhanced with the addition of 0.3% hydrogen peroxide to the phosphate buffer system.


Influence of clenbuterol, a beta-adrenergic agonist, on desipramine induced growth hormone, prolactin and cortisol stimulation.
We report herein the effects of the beta-adrenergic agonist clenbuterol on desipramine (DMI)-induced growth hormone (GH), prolactin (PRL) and cortisol secretion in healthy male subjects. In the first study, nine subjects were treated with either clenbuterol (0.04 mg, p.o.) or placebo. In the second study, 12 subjects received either DMI (50 mg, i.v.) alone or in combination with clenbuterol (0.04 mg, p.o.) given 60 min prior to DMI administration. Clenbuterol alone had no influence on GH, PRL, or cortisol concentrations, compared to placebo. DMI alone caused GH stimulation (mean maximum = 15.7 +/- 3.4 ng/ml), which was significantly lower after combined administration of DMI and clenbuterol (mean maximum = 7.7 +/- 1.6 ng/ml) (p less than or equal to 0.01). DMI-induced PRL and cortisol stimulation was not influenced by clenbuterol pretreatment. These results indicate the inhibiting influence of noradrenergic beta-receptors on GH stimulation.


Probiogenomic Analysis of Lactiplantibacillus sp. LM14-2 from Fermented Mussel (Hoi-dong), and Evaluation of its Cholesterol-lowering and Immunomodulation Effects.
Lactiplantibacillus sp. LM14-2, isolated from Thai-fermented mussel (Hoi-dong), showed attractive probiotic properties. This strain was identified as Lactiplantibacillus plantarum based on its phenotypic, chemotaxonomic, and genetic characteristics including whole-genome sequencing (WGS). The draft genome sequence was analyzed and annotated for the molecular mechanisms involved in the safety assessment, the adaptation and adhesion of L. plantarum LM14-2 to the gastrointestinal tract (GIT), and the beneficial genes involved in bacteria-host interactions. The L. plantarum LM14-2 exhibited bile salt hydrolase (BSH) activity, assimilated cholesterol at 86.07 ± 5.03%, stimulated the secretion of interleukin-12, interferon-gamma, and human beta defensin-2, and induced nitric oxide production. In addition, L. plantarum LM14-2 showed excellent gastrointestinal tolerance and adhesion ability to Caco-2 cells. Furthermore, the in silico analysis showed that L. plantarum LM14-2 was a non-human pathogen and did not contain antibiotic resistance genes or plasmids. L. plantarum LM14-2 also contained potential genes associated with various probiotic characteristics and health-promoting effects. Consequently, this study suggested that L. plantarum LM14-2 could be considered safe, with potential probiotic properties and health-promoting impacts, which could facilitate its probiotic application.


Carotid artery shortening: a safe adjunct to carotid endarterectomy.
Kinks and coils of the extracranial carotid artery system have been described in conjunction with atherosclerotic disease of the internal carotid artery. The purpose of this study was to determine whether adding a carotid artery shortening procedure to carotid endarterectomy affected perioperative mortality and stroke-morbidity rates or late restenosis. A retrospective chart review of all patients who concurrently underwent carotid endarterectomy and ipsilateral carotid artery shortening between 1983 and 1992 was performed. Long-term follow-up was obtained by contacting the primary physician or patient, and carotid artery duplex scans were obtained. One hundred seven patients were found to have undergone concurrent carotid endarterectomy and carotid artery shortening. The age range was 47 to 89 years, with 53 female and 54 male patients. Indications for surgery in this group were transient ischemic attacks in 28%, stroke in 18%, amaurosis fugax in 7%, and high-grade asymptomatic stenosis in 47%. Shortening procedures were performed by use of a variety of techniques at the completion of endarterectomy. The combined 30-day mortality and stroke morbidity rate was 2.7%, with two postoperative deaths and one stroke. In this same period, a total of 1072 carotid endarterectomies were performed, and the combined 30-day mortality and stroke morbidity rate was 4.0%. During late follow-up there were no ipsilateral strokes, recurrent symptoms, or significant restenoses. This experience suggests that the addition of a shortening procedure to carotid endarterectomy can be performed without increased morbidity and mortality rates and, when deemed appropriate, is a procedure with which the vascular surgeon should be familiar.


The termination of flexor tendon sheaths.
Fifty-five preserved cadaver digits were injected to show the termination of the flexor tendon sheath. The angle between the termination of the sheath and the most proximal dorsal and ventral bony points of the distal phalanx was measured. Using this concept of angles, a clinical guide to the region containing the sheath is given.


Silencing of SlSPX1 and SlSPX2 promote growth and root mycorrhization in tomato (Solanum lycopersicum L.) seedlings.
Owing to the essential requirement of phosphorus (P) for growth and development, plants tightly control inorganic phosphate (Pi) homeostasis. SPX-PHR regulatory circuit not only control phosphate homeostasis responses but also root mycorrhization by arbuscular mycorrhiza (AM) fungi. Besides sensing Pi deficiency, SPX (SYG1/Pho81/XPR1) proteins also control the transcription of P starvation inducible (PSI) genes by blocking the activity of PHR1 (PHOSPHATE STARVATION RESPONSE1) homologs in plants under Pi-sufficient conditions. However, the roles of SPX members in Pi homeostasis and AM fungi colonization remain to be fully recognized in tomato. In this study, we identified 17 SPX-domain containing members in the tomato genome. Transcript profiling revealed the high Pi-specific nature of their activation. Four SlSPX members have also induced in AM colonized roots. Interestingly, we found that SlSPX1 and SlSPX2 are induced by P starvation and AM fungi colonization. Further, SlSPX1 and SlSPX2 exhibited varying degrees of interaction with the PHR homologs in this study. Virus-induced gene silencing-based (VIGS) transcript inhibition of these genes alone or together promoted the accumulation of higher total soluble Pi in tomato seedlings and improved their growth. It also enhanced AM fungi colonization in the roots of SlSPX1 and SlSPX2 silenced seedlings. Overall, the present study provides evidence in support of SlSPX members being good candidates for improving AM fungi colonization potential in tomato.


Decreased activity of hippocampal neurons in Alzheimer's disease is not related to the presence of neurofibrillary tangles.
Numerous studies have established the key role of the Golgi apparatus (GA) in post-translational processing, transport and targeting of proteins destined for secretion, lysosomes and plasma membranes. Moreover, several studies performed in our laboratories have shown that the size of the immunocytochemically detected neuronal GA is a reliable index of neuronal activity in aging, Alzheimer's disease (AD) and amyotrophic lateral sclerosis. It has been suggested that in AD there is decreased neuronal activity, e.g. in terms of glucose metabolism and protein synthetic capability. To further explore the hypothesis of decreased neuronal activity in AD, in this study the size of the GA was measured in pyramidal neurons of the CA1 area of the hippocampus of non-demented controls and AD patients. The size of the GA was measured separately in neurons with and without neurofibrillary tangles (NFT). Moreover, in order to establish a correlation between the density of NFT and the size of the GA, the density of extraneuronal NFT was determined around each neuron and related to the size of its GA. The results, quantified by image analysis, indicate that there is a significant reduction in GA size in the neurons of the CA1 area of the hippocampus of AD patients. However, there was no significant relationship between the size of the GA and the presence or absence of intracellular NFT. In addition, there was no correlation between the density of extracellular NFT and GA size of adjacent neurons.(ABSTRACT TRUNCATED AT 250 WORDS)


Primary culture of chick, mouse or human neural crest cells.
A highly enriched population of neural crest cells (NCCs) from amniote embryos, such as from chicks, mice and humans, is desirable for experiments in fate determination. NCCs are also useful for testing the functional effects of molecular changes underlying numerous human diseases of neural crest derivatives and for investigating their potential for therapeutic compensation. This protocol details embryonic microdissection followed by neural tube explantation. Conditions favoring NCC expansion and the maintenance of their stem cell-like properties are described. Although neural crest-like cells can be derived from a number of sites in the mature organism, full potential is best ensured by their purification from their source tissue at the outset of migration. Going from embryo to established cell line takes 4 d; the first is the most labor-intensive day, but minimal intervention is required thereafter.


Scope of problem and history of patient safety.
Creating a safe environment in our incredibly complex health care system requires a major culture change. While it may be frustratingly slow and halting, that change is occurring and beginning to show results. This article addresses the issue of patient safety, discussing its history, and organizations and practices that are helping to make it more of a reality in today's health care environment.


Studies on glycoproteins in the human malaria parasite Plasmodium falciparum. Identification of a myristilated 45kDa merozoite membrane glycoprotein.
A murine monoclonal antibody has been used to characterise a 45,000 Da antigen that is associated with the surface membrane of merozoites of the human malaria parasite Plasmodium falciparum. The antigen is a glycoprotein and incorporates myristic acid.


Ileum and colon perforation following peritoneal dialysis-related peritonitis and high-dose calcium polystyrene sulfonate.
A rare but severe complication, intestinal necrosis, has been reported after sodium polystyrene sulfonate (SPS; Kayexalate) and sorbitol intake. Some case reports described bowel perforation following calcium polystyrene sulfonate (CPS; Kalimate) administration. We report a case of ileum and colon perforation following peritoneal dialysis-related peritonitis and high-dose Kalimate in a 59-year-old female patient. The patient had a history of hypertension, diabetes mellitus, and end-stage renal disease (ESRD). During hospitalization for peritoneal dialysis-related peritonitis, she developed hyperkalemia, and Kalimate was administered orally. However, severe abdominal distension and pain occurred just one day after Kalimate intake. An urgent surgery disclosed several perforations in the ileum and sigmoid colon. Pathology of the resected gut showed transmural necrosis and perforation with basophilic angulated crystals. The patient finally expired during hospitalization due to refractory septic shock.


Cronobacter sakazakii Infection in Early Postnatal Rats Impaired Contextual-Associated Learning: a Putative Role of C5a-Mediated NF-κβ and ASK1 Pathways.
This study was designed to test whether the Cronobacter sakazakii infection-impaired contextual learning and memory are mediated by the activation of the complement system; subsequent activation of inflammatory signals leads to alternations in serotonin transporter (SERT). To test this, rat pups (postnatal day, PND 15) were treated with either C. sakazakii (107 CFU) or Escherichia coli OP50 (107 CFU) or Luria bertani broth (100 μL) through oral gavage and allowed to stay with their mothers until PND 24. Experimental groups' rats were allowed to explore (PNDs 31-35) and then trained in contextual learning task (PNDs 36-43). Five days after training, individuals were tested for memory retention (PNDs 49-56). Observed behavioural data showed that C. sakazakii infection impaired contextual-associative learning and memory. Furthermore, our analysis showed that C. sakazakii infection activates complement system complement anaphylatoxin (C5a) (a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS1)) and mitogen-activated protein kinase kinase1 (MEKK1). Subsequently, MEKK1 induces pro-inflammatory signals possibly through apoptosis signal-regulating kinase-1 (ASK-1), c-Jun N-terminal kinase (JNK1/3) and protein kinase B gamma (AKT-3). In parallel, activated nuclear factor kappa-light-chain-enhancer B cells (NF-κB) induces interleukin-6 (IL-6) and IFNα-1, which may alter the level of serotonin transporter (SERT). Observed results suggest that impaired contextual learning and memory could be correlated with C5a-mediated NF-κβ and ASK1 pathways.


Emotion regulation, physiological arousal and PTSD symptoms in trauma-exposed individuals.
Retrospective studies suggest a link between PTSD and difficulty regulating negative emotions. This study investigated the relationship between PTSD symptoms and the ability to regulate negative emotions in real-time using a computerised task to assess emotion regulation. Trauma-exposed ambulance workers (N = 45) completed self-report measures of trauma exposure, PTSD symptoms and depression. Participants then completed a computer task requiring them to enhance, decrease or maintain their negative emotions in response to unpleasant images. Skin conductance responses (SCR) were recorded and participants also made ratings of emotion intensity. Immediately after the computer task, participants were asked to describe the strategies they had used to regulate their negative emotions during the task and recorded spontaneous intrusions for the unpleasant images they had seen throughout the following week. PTSD symptoms were associated with difficulty regulating (specifically, enhancing) negative emotions, greater use of response modulation (i.e., suppression) and less use of cognitive change (i.e., reappraisal) strategies to down-regulate their negative emotions during the task. More intrusions developed in participants who had greater reductions in physiological arousal whilst decreasing their negative emotions. PTSD was measured by self-report rather than by a clinician administered interview. The results suggest a relationship between emotion regulation ability and PTSD symptoms rather than emotion regulation and PTSD. Difficulty regulating negative emotions may be a feature of trauma-exposed individuals with PTSD symptoms, which may be linked to the types of strategies they employ to regulate negative emotions.


Increased incidence of sporadic Creutzfeldt-Jakob disease in the age groups between 70 and 90 years in Belgium.
From 1998 a prospective surveillance study of Creutzfeldt-Jakob disease (CJD) has been initiated in Belgium. In addition to epidemiological data, information on cerebrospinal fluid biomarkers, prion protein gene and brain neuropathology was collected. From 1-1-1998 to 31-12-2004, 188 patients were referred to the surveillance system. In 85 patients a 'definite' diagnosis of sporadic CJD (sCJD) could be made, whereas 26 patients remained 'probable'. We further identified two unrelated patients with an E200K mutation, and two patients with a seven octapeptide repeat insertion in one family. In one patient a familial history was noted but genetic analysis was not performed. In 72 patients different final diagnoses were made, Alzheimer's disease being the most frequent (N = 20). The demographic parameters of the Belgian population were similar to those observed in the rest of Europe. We did notice a significantly increased age-specific incidence (> 6/10(6)/year) of sCJD patients between 70 and 90 years old in the period 2002-2004 compared to 1998-2001 and retrospectively obtained data (1990-1997, p < 0.01). We undertook a detailed clinical and biochemical analysis to investigate this increase but could not identify any reason other than an increased vigilance for the diagnosis. In conclusion, our study identified that in the past sCJD may have been underestimated in patients over age 70 although these patients are both clinically and neurobiochemically similar to the general sCJD phenotype.


[Disseminated tuberculosis in non-immunocompromised host: three case reports].
Disseminated tuberculosis, i.e., tuberculosis involving lung, liver, spleen, bone marrow and lymph nodes is rare (2.8%), particularly when immunocompromised diathesis is lacking. We report three cases of disseminated tuberculosis confirmed by bacteriology or histology, which occurred in non-immunocompromised patients. Disease evolution under antituberculous treatment was favorable in two cases and fatal in the third one. Disseminated tuberculosis must be suspected when miliary pulmonary lesions are associated with hematologic abnormalities, even in non-immunocompromised host. Early treatment is mandatory to avoid fatal outcome.


[Devices facilitating the preparation of biological specimens for electron microscopy].
The construction of a matrix is described which facilitates the process of placing biological objects into polymer media in order to prepare ultrathin sections without the employment of gelatin, starch and polyethylene capsules that can be used only once. The construction of a reactor for cytochemical assays is presented. The apparatus can be used to locate enzymes within the cell, and to identify microorganisms. A modification of the dialysis technique for microbiological objects is proposed which accelerates and simplifies the process.


[Myelography with metrizamide in children (author's transl)].
The non-ionic water-soluble contrast medium metrizamide (Amipaque) allows the examination of all regions of the spinal canal. Excellent visualization, the low toxicity for nervous tissue, and small side effects make metrizamide the best contrast medium for myelography, even in infants and children. The technique used is described and results are demonstrated.


Reducing the costs of paediatric antibiotic prescribing in the community by implementing guideline recommendations.
Italian children receive a high number of antibiotic prescriptions, and the use of second-choice antibiotics is common. A few studies in other countries have demonstrated that the implementation of international guidelines for the most common paediatric diseases may reduce the associated costs. A cost analysis of the expenditure for antibiotic prescriptions in outpatient children in the Lombardy region (Italy) and for each of the region's local health units (LHUs) was performed using a pharmacoepidemiological approach. The safety and cost impact associated with a quali-quantitative improvement in antibiotic prescribing was estimated. The data source was the Lombardy region's prescription database (year 2008) for outpatient children <14 years old. The average total expenditure for each package, and per capita, was calculated for each active substance considered and for each LHU. An estimate of the possible cost reduction was elaborated using, as a reference, the prescription profile of a group of paediatricians that has been involved in initiatives concerning care for years. The hospital admission rates for acute respiratory infections (ARI) and their major complications were evaluated at the regional level and in the group of children followed by the reference paediatricians. The cost reduction estimate reveals a possible decrease in antibiotic expenditure of about 3·6 million euros (-19·5%) in the Lombardy region. Large variability was observed between different LHUs (-33·3 to +9·2% of difference). The hospital admission rate was not different when comparing the group of children followed by the reference paediatricians to the rest of the study population, but the hospital admission rate for ARI was lower in the reference group (χ(2) = 16·4, P < 0·001). This is the first Italian study to evaluate the costs related to a specific prescription profile, which already exists in the real setting, hypothesizing its application in a large outpatient child population of the same geographical area. The results show that by improving prescribing appropriateness, it is possible to reduce the expenditure associated with antibiotic prescriptions to outpatient children in the Lombardy region by about one-fifth. The lower rate of hospital admissions for ARI suggests that the adopted profile is also beneficial to children's health.


Retino-cephalic vascular malformation.
Unilateral vascular malformation of the retina, brain and parts of the face constitute a rare syndrome named after Wyburn-Mason or as Bonnet-Dechaume-Blanc syndrome. We report this case because of its rarity.


Detection of persistent SARS-CoV-2 IgG antibodies in oral mucosal fluid and upper respiratory tract specimens following COVID-19 mRNA vaccination.
COVID-19 mRNA vaccines are highly effective at preventing COVID-19. Prior studies have found detectable SARS-CoV-2 IgG antibodies in oral mucosal specimens of participants with history of COVID-19. To assess the development of oral SARS-CoV-2 IgG antibodies among people who received either the Moderna or Pfizer/BioNTech COVID-19 vaccination series, we developed a novel SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) to quantify the concentrations of oral and nasal mucosal SARS-CoV-2 IgG levels. We enrolled 52 participants who received the Moderna vaccine and 80 participants who received the Pfizer/BioNTech vaccine. Oral mucosal specimens were self-collected by participants prior to or on the day of vaccination, and on days 5, 10, 15, and 20 following each vaccination dose and 30, 60, and 90 days following the second vaccination dose. A subset of the cohort provided additional nasal mucosal specimens at every time point. All participants developed detectable oral mucosal SARS-CoV-2 IgG antibodies by 15 days after the first vaccination dose. There were no significant differences in oral mucosal antibody concentrations once participants were fully vaccinated in the Moderna and Pfizer/BioNTech vaccines. Oral or nasal mucosal antibody testing could be an inexpensive and less invasive alternative to serum antibody testing. Further research is needed to understand the duration of detectable oral or nasal mucosal antibodies and how antibody concentrations change with time.


Ultrasound Color histogram assessment allows better view of echotexture damage.
The colored ultrasound images can better highlight the joint echotexture damage. To detect echotexture changes in joints of patients with rheumatic diseases, through a color histogram, and to correlate the area measurements with the gray scale (GS). Four patients with chondrocalcinosis, 5 patients with osteoarthritis and 1 patient with psoriatic arthritis were evalutated. A total of 104 synovitis (SYN) and calcifications (calcif) measurements in cm2 were performed in the dorsal radiocarpal joint (DRR); triangular fibrocartilage complex (TFC); dorsal metacarpophalangeal joints (MCP) and lateral and medial knee suprapatellar recesses. For each GS measure, one was performed for each standard color image. Spearman was used for correlation analysis. Mean±SD of image patterns: RGB (Red, Green and Blue) SYN 16.96±0.25cm2; indigo SYN 6.43±0.07cm2, RGB Calcif 0.03±0.00cm2; indigo Calcif 0.06±0.03cm2; GS SYN 16.13±0.35cm2 and GS Calcif 0.56±0.01cm2. Correlations of color images patterns RGB DRR SYN and indigo DRR SYN: r=1, p<0.001; indigo DRR SYN and RGB suprapattelar SYN: r=1, p<0.001; RGB MCP SYN and indigo MCP SYN: r=1, p<0.001; indigo DRR calcif and RGB TFC calcif: r=1 p<0.001; the RGB and indigo measurement standards when correlated with GS for SYN and calcifs were not statistically significant (p=0.333 to 0.667). The RGB and indigo patterns seem to better define these echotexture damage.


The anxiolytic effect on the fear-potentiated startle is not due to a non-specific disruption.
In the present study, the effects of alprazolam, chlordiazepoxide, ethanol and haloperidol in the strychnine-potentiated startle response paradigm were investigated. Because strychnine increases control startle levels without fear-conditioning, no central state of fear exists. When anxiolytic drugs reduce the fear-induced potentiation of the startle response without reducing the strychnine-induced startle potentiation, their attenuating effect on startle potentiation in the fear-potentiated startle response paradigm can more likely be attributed to their anxiolytic properties. The selected drugs, which effectively reduced the fear-induced startle potentiation in an earlier study, indeed did not selectively affect the strychnine-induced startle potentiation, supporting the notion that the dose-dependent reduction of startle potentiation due to anxiolytic drugs in the fear-potentiated startle response paradigm does not reflect a "non-specific" disruption of startle behavior.