Atypical Presentation of Pulmonary Embolism Several Months After COVID-19 Infection.
A 47-year-old female with a past medical history of morbid obesity and hypertension presented with acute onset dizziness that started while she was at work one evening. She did not have chest pain or dyspnea. She had vital signs within an acceptable range, oxygen saturation of 98%-99%, and was not in acute distress. Examination including the Dix-Hallpike maneuver was unremarkable. Computed tomography angiography (CTA) of the head and neck disclosed bilateral pulmonary embolism without any evidence of cerebral ischemia. CTA chest confirmed the diagnosis of bilateral pulmonary emboli. Importantly, besides the obesity, the patient did not have any other risk factors of pulmonary embolism including recent immobilization, surgery, hormonal therapy or contraceptive use, and personal or family history of thromboembolic disorders. However, she was diagnosed with COVID-19 infection six months back with symptoms not requiring hospitalization. Following further workup for her dizziness and neurology evaluation, in the absence of any other plausible etiology, her presenting symptom was attributed to the atypical presentation of pulmonary embolism. She was treated with heparin in the hospital and discharged on apixaban. Her symptoms had resolved at the time of discharge.


PITX2 and non-canonical Wnt pathway interaction in metastatic prostate cancer.
The non-canonical Wnt pathway, a regulator of cellular motility and morphology, is increasingly implicated in cancer metastasis. In a quantitative PCR array analysis of 84 Wnt pathway associated genes, both non-canonical and canonical pathways were activated in primary and metastatic tumors relative to normal prostate. Expression of the Wnt target gene PITX2 in a prostate cancer (PCa) bone metastasis was strikingly elevated over normal prostate (over 2,000-fold) and primary prostate cancer (over 200-fold). The elevation of PITX2 protein was also evident on tissue microarrays, with strong PITX2 immunostaining in PCa skeletal and, to a lesser degree, soft tissue metastases. PITX2 is associated with cell migration during normal tissue morphogenesis. In our studies, overexpression of individual PITX2A/B/C isoforms stimulated PC-3 PCa cell motility, with the PITX2A isoform imparting a specific motility advantage in the presence of non-canonical Wnt5a stimulation. Furthermore, PITX2 specific shRNA inhibited PC-3 cell migration toward bone cell derived chemoattractant. These experimental results support a pivotal role of PITX2A and non-canonical Wnt signaling in enhancement of PCa cell motility, suggest PITX2 involvement in homing of PCa to the skeleton, and are consistent with a role for PITX2 in PCa metastasis to soft and bone tissues. Our findings, which significantly expand previous evidence that PITX2 is associated with risk of PCa biochemical recurrence, indicate that variation in PITX2 expression accompanies and may promote prostate tumor progression and metastasis.


Diagnostic performance of gray-scale versus combined gray-scale with colour doppler ultrasonography in the diagnosis of malignancy in thyroid nodules.
To compare diagnostic performance of gray-scale ultrasound and combined gray-scale ultrasound with color Doppler ultrasound in predicting malignancy of thyroid nodules by using tissue diagnosis as the reference standard. Diagnostic test with prospective data collection. Between November 2007 and October 2008, 31 patients (16 with solitary thyroid nodules and 15 with multiple thyroid nodules) were preoperatively evaluated with gray-scale ultrasound and color Doppler ultrasound. The nodules were classified as benign or malignant according to the established ultrasound criteria and were later compared with histologic findings obtained from surgical specimens. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of gray-scale US and combined gray-scale with color Doppler US were evaluated using histology as the reference. The sensitivity, specificity, PPV and NPV of gray-scale ultrasonography were 80.0%, 84.6%, 50.0% and 95.7%, respectively. The sensitivity, specificity, PPV and NPV of preoperative combined gray-scale US with color Doppler ultrasonography were 40.0%, 96.2%, 66.7% and 89.3%, respectively. Combination of gray-scale US with color Doppler US findings improves specificity and PPV in the diagnosis of malignancy in thyroid nodules.


Families of children with developmental disabilities: an examination of family hardiness.
Using the Typology Model of Adjustment and Adaptation, a family stress model, relationships among family hardiness, family stressors, family appraisal, coping, social support, and satisfaction with family functioning were examined in a sample of 57 families of children with developmental disabilities. Family hardiness was associated with family appraisal, social support, parental coping related to maintaining family integration, and satisfaction with family functioning. Higher satisfaction with family functioning was correlated with coping-integration, network support, functional support, and hardiness. Lower satisfaction with family functioning was associated with higher family stressor scores, social support loss, and increased parental age. Over 42% of the variance in family functioning was accounted for by family hardiness, functional support, family stressors, and parental age. The results highlight the value of continued investigations of hardiness in families.


[Venous ulcer on the hand due to a treatment-related arteriovenous fistula].
An arteriovenous fistula of the arm for hemodialysis needs to last long and provide easy access for puncture. A 50 year-old woman, with type 2 diabetes complicated by chronic renal failure, presented with an ulcer on the dorsum of the right hand that had developed over the past year. Humeral artery to basilica vein, side-to-side, arteriovenous fistula in the right arm was created in 1996. In 1999, she received a renal transplant. In 2002, she developed a deep ulcer on the dorsum of the right hand that progressed over one year, without improvement good local treatment. Doppler echography and a fistulography revealed proximal stenosis of the basilica vein, and a less restricted distal stenosis before the shunt. A venous ulcer on the dorsum of the hand due excessive venous pressure in the draining area. The complications of arteriovenous fistulas can be severe. Arterial stenosis is frequent and is the consequence of intimal hypertrophy. Chronic ischemia symptoms can be observed, but the hemodynamic loss is usually asymptomatic. When clinical signs are noisy emergency surgery is required. Venous stenosis is responsible for ischemia through venous overload, leading to edema of the arm, and rarely to venous-ulcer type trophic disorders as seen in this patient. Screening for stenosis on the vascular vein network must be systematic before creating an arteriovenous fistula.


Drosophila CtBP regulates proliferation and differentiation of eye precursors and complexes with Eyeless, Dachshund, Dan, and Danr during eye and antennal development.
Specification factors regulate cell fate in part by interacting with transcriptional co-regulators like CtBP to regulate gene expression. Here, we demonstrate that CtBP forms a complex or complexes with the Drosophila melanogaster Pax6 homolog Eyeless (Ey), and with Distal antenna (Dan), Distal antenna related (Danr), and Dachshund to promote eye and antennal specification. Phenotypic analysis together with molecular data indicate that CtBP interacts with Ey to prevent overproliferation of eye precursors. In contrast, CtBP,dan,danr triple mutant adult eyes have significantly fewer ommatidia than CtBP single or dan,danr double mutants, suggesting that the CtBP/Dan/Danr complex functions to recruit ommatidia from the eye precursor pool. Furthermore, CtBP single and to a greater extent CtBP,dan,danr triple mutants affect the establishment and maintenance of the R8 precursor, which is the founding ommatidial cell. Thus, CtBP interacts with different eye specification factors to regulate gene expression appropriate for proliferative vs. differentiative stages of eye development.


Identification and characterisation of phenolics in Polygonum capitatum by ultrahigh-performance liquid chromatography with photodiode array detection and tandem mass spectrometry.
Polygonum capitatum is a well-known Chinese medicinal plant widely used by the Miao people for the treatment of various urologic disorders. Previous investigations have shown the presence of various types of phenolics. Our ultrahigh-performance liquid chromatography with photodiode array detection and mass spectrometry (UPLC-PDA-MS) analysis indicated that flavonoid glycosides and polyphenolic glycosides were its major constituents and quite a number of phenolic compounds have not yet been identified. Identification or characterisation of the major compounds of this plant will contribute to the scientific understanding of the medicinal plant and the authentication of the plant material and its pharmaceutical preparations. To develop an efficient method for the identification and structural characterisation of the major compounds present in P. capitatum. Elution of the 70% ethanol extract of P. capitatum by 80% ethanol on a D101 macroporous resin column afforded a phenolics-enriched fraction, separation of which by Sephadex LH-20 column chromatography eluted with absolute ethanol gave a tannin-free phenolic fraction (TFPF). Compounds present in TFPF were identified and structurally characterised by UPLC-PDA-ESI-MS/MS. An amino acid and 40 phenolics including a number of flavonoid glycosides and polyphenolic glycosides were identified or structurally characterised in TFPF. Among these compounds, four were new and 19 were described in the plant for the first time. The study showed that TFPF of P. capitatum contained flavonoid glycosides and polyphenolic glycosides as its major principles. Polyphenolic glycosides were perhaps the most typical chemical markers of P. capitatum.


Phenotypic heterogeneity in cultured skin fibroblasts from patients with disorders of peroxisome biogenesis belonging to the same complementation group.
We have studied fibroblast cell lines derived from a control subject (cell line 85AD5035F) and three patients clinically described as having the Zellweger syndrome (cell line W78/515), the infantile form of Refsum disease (cell line BOV84AD) and hyperpipecolic acidaemia (cell line GM3605), respectively. The mutant cell lines belonged to the same complementation group. The fibroblasts were cultured under identical conditions and were harvested at different time intervals after reaching confluence. Several peroxisomal parameters were determined. In agreement with previous reports, a lowered enzymic activity of acyl-CoA: dihydroxyacetonephosphate acyltransferase and a decrease in latent catalase clearly distinguished the patient cell lines from the control cell line. However, the cell lines exhibited a phenotypic heterogeneity. This was most strikingly encountered when cells were processed for indirect immunofluorescence microscopy and stained with anti-(catalase). The control cells exhibited a punctate fluorescence, which is indicative of the presence of catalase in peroxisomes. In the mutant cell line W78/515 a diffuse fluorescence was observed, indicative of the presence of catalase in the cytosol. In the other two mutant cell lines a punctate fluorescence was observed in some of the cells. Moreover, clear differences in the extent of proteolytic processing of acyl-CoA oxidase were detected. The mutant cell line BOV84AD displayed a control-like pattern with all molecular forms of acyl-CoA oxidase (72, 52 and 20 kDa) present, whereas in the W78/515 cell line only the 72 kDa component could be visualised. The GM3605 cell line was intermediate in this respect.


Medicare and Medicaid programs; benefit period determinations, drug regimen reviews and other technical changes--HCFA. Final rule.
Under the Hospital Insurance Program (Medicare--Part A), payment for covered inpatient hospital and skilled nursing facility (SNF) services is available for a limited number of days during each benefit period or "spell of illness." Current Medicare regulations reflect the statutory provision under section 1861(a) of the Social Security Act (Act) that a beneficiary's benefit period begins on the day he or she is furnished inpatient hospital or SNF services and ends when he or she has not been "an inpatient of a hospital nor an inpatient of a skilled nursing facility" (as defined under sections 1861(e)(1) and (j)(1) of the Act, respectively) for 60 consecutive days. These final regulations: Specify that a beneficiary is an "inpatient" of a SNF and is therefore prolonging a spell of illness in a SNF only if the care received by the beneficiary meets skilled level of care conditions and establish certain presumptions which Medicare intermediaries may use in determining whether skilled level of care conditions have been met during a SNF stay. These regulations also provide that a pharmacist must perform drug regimen reviews in intermediate care facilities (ICFs). In addition Section 405.702 of the regulations is amended to remove certain cross-references that are now outdated and unnecessary.


Borane-Catalyzed Carbazolation Reactions of Aryldiazoacetates.
Herein, we report on the tris(pentafluorophenyl)borane-catalyzed reaction of carbazole heterocycles with aryldiazoacetates. We could demonstrate that selective N-H functionalization occurs in the case of an unprotected carbazole, other N-heterocycles, and secondary amines in good yields. In contract, the protected carbazole undergoes C-H functionalization at the C-3 position in a good yield. The application of both approaches was studied in 41 examples with up to a 97% yield.


Auditory illusions as evidence for a role of the syllable in adult developmental dyslexics.
This study investigated whether adult developmental dyslexics differ from normal controls in early stages of spoken language processing that in turn might be related to specific reading difficulties. Subjects were required to detect prespecified targets under dichotic presentation of auditory nonword pairs. The stimuli were made such that segment migrations were possible. The potential contribution of phonetic features, as well as that of phonemes and syllables, was investigated. The results showed that dyslexics had specifically more syllable-based migrations. This result is discussed in the context of well-documented metaphonological deficits and memory problems of poor readers.


[A case of transitional cell carcinoma of the renal pelvis with adenocarcinoma producing CEA and CA19-9].
We report a case of invasive renal pelvic tumor with high serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9). An 86-year-old man presented with macrohematuria. Retrograde pyelography demonstrated a filling defect in right upper calyx, suspected of renal pelvic tumor. The levels of serum CEA and CA 19-9 were elevated to 28.0 ng/ml and 122 U/ml, respectively. No abnormalities were found in the gastrointestinal tract. Right nephroureterectomy was performed, and histopathological diagnosis was transitional cell carcinoma, grade 2>grade 3, accompanied with adenocarcinoma immuno-stained for CEA and CA19-9. A part of the tumor showed a tubular growth pattern. Both serum levels of CEA and CA 19-9 immediately decreased to the normal range after the operation, but increased again with lung and hepatic metastases.


Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis-associated encephalopathy.
Fisetin, the effective ingredient of the traditional Chinese medicine named Cotinus coggygria, is recommended to be active therapeutic in many disorders. However, its role in sepsis-associated encephalopathy (SAE) remains unclarified. Cecal ligation and puncture (CLP) operation was performed to establish a rat model of SAE. Rats were grouped according to the surgery operation and fisetin administration. Cognitive impairment was assessed by Morris water maze test. Disruption of blood-brain barrier (BBB) integrity was detected by Evan's blue staining. The mitophagy, reactive oxygen species (ROS) generation, NLRP3 inflammasome activation, and pro-inflammatory cytokines levels were measured through western blot and double immunofluorescence labeling. A transmission electron microscope was applied for the observation of mitochondrial autophagosomes. Rats in the CLP group presented increased expression of IL-1R1, pNF-κB, TNF-α, and iNOS in microglial cells, indicating severe inflammation in the central nervous system (CNS). Nevertheless, there was no increase in BBB permeability. Meanwhile, NLRP3 inflammasome was activated in cerebral microvascular endothelial cells (CMECs), presented with an elevation of caspase-1 expression and IL-1β secretion into CNS. In addition, we found fisetin significantly improved cognitive dysfunction in rats with SAE. Neuroprotective effects of fisetin might be associated with inhibition of neuroinflammation, represented with decreased expression of IL-1R1, pNF-κB, TNF-α, and iNOS in microglia. Furthermore, fisetin induced mitophagy, scavenged ROS, blocked NLRP3 inflammasome activation of CMECs, as evidenced by decreased expression of caspase-1 and reduced release of IL-1β into CNS. Collectively, fisetin-blocked NLRP3 inflammasome activation via promoting mitophagy in CMECs may suppress the secretion of IL-1β into CNS, reduce neuroinflammation, and contribute to the amelioration of cognitive impairment.


Embossed radiography utilizing energy subtraction.
Currently, it is difficult to carry out refraction-contrast radiography by using a conventional X-ray generator. Thus, we developed an embossed radiography system utilizing dual-energy subtraction for decreasing the absorption contrast in unnecessary regions, and the contrast resolution of a target region was increased by use of image-shifting subtraction and a linear-contrast system in a flat panel detector (FPD). The X-ray generator had a 100-microm-focus tube. Energy subtraction was performed at tube voltages of 45 and 65 kV, a tube current of 0.50 mA, and an X-ray exposure time of 5.0 s. A 1.0-mm-thick aluminum filter was used for absorbing low-photon-energy bremsstrahlung X-rays. Embossed radiography was achieved with cohesion imaging by use of the FPD with pixel sizes of 48 x 48 microm, and the shifting dimension of an object in the horizontal direction ranged from 100 to 200 microm. At a shifting distance of 100 mum, the spatial resolutions in the horizontal and vertical directions measured with a lead test chart were both 83 microm. In embossed radiography of non-living animals, we obtained high-contrast embossed images of fine bones, gadolinium oxide particles in the kidney, and coronary arteries approximately 100 microm in diameter.


[Effects of chloride ion channel and its blockers on myocardial ischemia reperfusion arrhythmias in rabbits].
To explore the impact of chloride ion channel and its blockers 4, 4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS), cyanato-stilbene-2, 2'-disulfonic acid (SITS) and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB) on arrhythmias caused by myocardial ischemia reperfusion. A total of 40 rabbits were divided into control, ischemia reperfusion, DIDS low-dose, DIDS high-dose, SITS low-dose, SITS high-dose, NPPB low-dose and NPPB high-dose groups. Myocardial ischemia reperfusion model was established by ligation of anterior descending coronary artery. And standard limb lead II of electrocardiogram (ECG) was continuously monitored during the experimental process. Then comparisons of heart rate, ECG P wave, R wave, T wave, ST segment changes and arrhythmias score were made between the above groups. During 30-minute ischemia, compared with the control group, all other groups showed significantly decreased heart rate ((199.8 ± 4.0) - (253.6 ± 2.1) vs (267.0 ± 3.4), all P < 0.01), elevated ECG P wave ((0.216 ± 0.019) - (0.356 ± 0.024) vs (0.186 ± 0.019), all P < 0.01), R wave ((0.564 ± 0.017) - (1.138 ± 0.048) vs (0.506 ± 0.018), all P < 0.01), T wave ((0.542 ± 0.013) - (0.856 ± 0.045) vs (0.278 ± 0.015), all P < 0.01) and ST segment ((0.326 ± 0.027) - (0.668 ± 0.054) vs (0.024 ± 0.023), all P < 0.01) and increased arrhythmia score ((1.4 ± 0.5) - (4.6 ± 0.5) vs (0.4 ± 0.5), all P < 0.01). Compared with the ischemia reperfusion group, the above indices significantly improved in the intervention groups (heart rate: (214.8 ± 3.4) - (246.8 ± 4.0) vs (199.8 ± 4.0), all P < 0.01; P wave: (0.216 ± 0.019) - (0.316 ± 0.011) vs (0.356 ± 0.024), all P < 0.01; R wave: (0.564 ± 0.017) - (0.980 ± 0.035) vs (1.138 ± 0.048), all P < 0.01; T wave: (0.542 ± 0.013) - (0.792 ± 0.026) vs (0.856 ± 0.045), all P < 0.01; ST segment: (0.326 ± 0.027) - (0.596 ± 0.018) vs (0.668 ± 0.054), all P < 0.01; arrhythmia score: (1.4 ± 0.5) - (3.8 ± 0.4) vs (4.6 ± 0.5), all P < 0.01). Among which, the DIDS group was the best, followed by the SITS group and then the NPPB group. And the high-dose subgroups were better than those of the low-dose subgroups. During 60-minute reperfusion, the decreased heart rate upswing significantly in each group and the elevated P wave, R wave, T wave and ST segment fell back gradually. The DIDS group showed the most obvious amplitude change, followed by the SITS group and then the NPPB group. And the high-dose subgroups were better than those of the low-dose subgroups. The arrhythmia score during reperfusion showed the same trend. Chloride ion channel is involved in the generation of myocardial ischemia reperfusion arrhythmia.Early application of chloride ion channel blockers DIDS, SITS and NPPB may improve the ECG manifestations and reduce the degree of reperfusion arrhythmia.


Vectofusin-1, a potent peptidic enhancer of viral gene transfer forms pH-dependent α-helical nanofibrils, concentrating viral particles.
Gene transfer using lentiviral vectors has therapeutic applications spanning from monogenic and infectious diseases to cancer. Such gene therapy has to be improved by enhancing the levels of viral infection of target cells and/or reducing the amount of lentivirus for greater safety and reduced costs. Vectofusin-1, a recently developed cationic amphipathic peptide with a pronounced capacity to enhance such viral transduction, strongly promotes the entry of several retroviral pseudotypes into target cells when added to the culture medium. To clarify the molecular basis of its action the peptide was investigated on a molecular and a supramolecular level by a variety of biophysical approaches. We show that in culture medium vectofusin-1 rapidly forms complexes in the 10 nm range that further assemble into annular and extended nanofibrils. These associate with viral particles allowing them to be easily pelleted for optimal virus-cell interaction. Thioflavin T fluorescence, circular dichroism and infrared spectroscopies indicate that these fibrils have a unique α-helical structure whereas most other viral transduction enhancers form β-amyloid fibrils. A vectofusin-1 derivative (LAH2-A4) is inefficient in biological assays and does not form nanofibrils, suggesting that supramolecular assembly is essential for transduction enhancement. Our observations define vectofusin-1 as a member of a new class of α-helical enhancers of lentiviral infection. Its fibril formation is reversible which bears considerable advantages in handling the peptide in conditions well-adapted to Good Manufacturing Practices and scalable gene therapy protocols.


Growth in glucose-based medium and exposure to subinhibitory concentrations of imipenem induce biofilm formation in a multidrug-resistant clinical isolate of Acinetobacter baumannii.
Acinetobacter baumannii is emerging as an important nosocomial pathogen. Multidrug resistance, as well as ability to withstand environmental stresses, makes eradication of A. baumannii difficult, particularly from hospital settings. Over a six-year period, 73 isolates of A. baumannii were collected from infected patients in two hospitals in Italy. While 69 out of the 73 isolates displayed identical multidrug antibiotic resistance pattern, they were susceptible to carbapenems. Genetic profiles of these 69 isolates, determined by Pulsed Field Gel Electrophoresis (PFGE), indicated that they were genetically related and could be clustered in a specific clone, called SMAL. We tested the ability of the SMAL clone to form biofilm, an important determinant for bacterial colonization of the human host and for persistence in the hospital environment. Biofilm formation by A. baumannii SMAL, measured as surface adhesion to polystyrene, is strongly affected by growth conditions, being impaired in rich growth media such as LB, while being favoured in glucose-based medium. Surface adhesion in glucose-based media is inhibited by treatment with cellulase, suggesting that it depends on production of cellulose or of a chemically related extracellular polysaccharide. Exposure of A. baumannii SMAL to subinhibitory concentrations of imipenem resulted in biofilm stimulation and increased production of iron uptake proteins. Growth in iron-supplemented medium also stimulated surface adhesion, thus suggesting that increased intracellular iron concentrations might act as an environmental signal for biofilm formation in A. baumannii SMAL. Our results indicate that exposure to subinhibitory concentrations of imipenem can stimulate biofilm formation and induce iron uptake in a pathogenic strain of A. baumannii, with potential implications on antibiotic susceptibility and ability to persist in the human host.


Inhibition by CO and polarization in Pd-based membranes: a novel permeation reduction coefficient.
In this Article, a novel permeation reduction coefficient (PRC) is defined and used to take into account the presence of both inhibition by CO and concentration polarization in hydrogen permeation through Pd-based membranes. The usefulness of this coefficient consists in the possibility of describing simply, but at the same time powerfully, the behavior of the membrane subject to the combined effect of inhibition and polarization. According to this approach, the effective permeance, which is generally unknown because it depends on these two phenomena, can be directly evaluated by multiplying the "clean" intrinsic membrane Sieverts permeance (measurable by simple pure hydrogen permeation tests) by a PRC function, that is, [effective permeance] = (1-PRC) [clean Sieverts permeance]. The values of PRC are evaluated by means of a complex model that takes into account the several elementary permeation steps, in which the inhibitory effect of CO is also considered as well as the concentration polarization. The membrane behavior is evaluated in terms of some "performance maps", where PRC and other two coefficients (concentration polarization coefficient (CPC) and inhibition coefficient (IC)) are reported as functions of several operating conditions (hydrogen molar fraction, CO partial pressure, and upstream total pressures). Therefore, these maps provide a useful tool to estimate directly the main design parameter (the overall permeance) in situations where complex transport and kinetic phenomena affect the membrane performances, allowing the membrane performance to be estimated much better and the separation equipment to be better designed.


Evidence for tip velocity oscillations in dendritic solidification.
Dendritic growth experiments were conducted in the reduced-convection environment aboard the space shuttle Columbia on STS-87. Spectral analysis was performed on 30-frame/s video data during growths of isothermal dendrites. Results indicate that pivalic acid dendrites exhibit a subtle oscillatory behavior of the axial growth velocity near the tip, with a frequency component that is associated with the sidebranch formation process.


Prevalence of epilepsy in the elderly: the Rotterdam Study.
We assessed the prevalence of epilepsy in an elderly population in The Netherlands. The study was conducted from 1991 to 1993 as part of the Rotterdam Study, a population-based door-to-door study of all elderly people living in Ommoord, a suburb of Rotterdam, and included 5,559 persons aged 55-95 years. All subjects were screened for epilepsy through direct questions regarding the existence of epilepsy and antiepileptic drug (AED) use, in addition to relevant questions from the World Health Organization (WHO) protocol for epidemiologic studies of neurologic diseases. Further evaluation of screen positives was made by a panel of 1 study physician and 4 epileptologists, who also classified all confirmed cases of epilepsy according to the classifications of the International League Against Epilepsy (ILAE). The overall prevalence of active epilepsy in our study population was 0.9% including special syndromes and 0.8% excluding special syndromes. The prevalence increased with age from 0.7% for those aged 55-64 years to 1.2% for those aged 85-94 years. The increase with age was detected among men and women both. Our study confirms other findings showing that the prevalence of active epilepsy increases with age in the elderly. The prevalence figures in our study were high as compared with those of other population-based studies. Epilepsy appears to be a major cause of morbidity in the elderly.


Avoiding complications in patellofemoral surgery.
The diagnosis and treatment of patellofemoral disorders can challenge even the experienced orthopedic surgeon. Differential diagnosis is broad and multiple anatomic abnormalities must be taken into account in order to manage care. The majority of patients with patellofemoral disorders can be treated successfully nonoperatively. When nonoperative management fails, and in the carefully selected patient, a variety of surgical options exist based on the anatomic pathology involved, but each brings its own potential for complication. We discuss several of the surgical treatment options that are available to the orthopedic surgeon for the treatment of patellofemoral disorders, including lateral retinacular release, medial soft-tissue reconstructive procedures, and bony procedures (including trochleoplasty and tibial tubercle osteotomy. We describe potential complications of each procedure and what the orthopedic surgeon can do to avoid them.


Insight into the role of grafting and arbuscular mycorrhiza on cadmium stress tolerance in tomato.
Physiological, biochemical, metabolite changes, and gene expression analysis of greenhouse tomato (Solanum lycopersicum L.) were investigated in two grafting combinations (self-grafted 'Ikram' and 'Ikram' grafted onto interspecific hybrid rootstock `Maxifort'), with and without arbuscular mycorrhizal (AM), exposed to 0 and 25 μM Cd. Tomato plants responded to moderate Cadmium (Cd) concentration by decreasing yield and crop growth parameters due to the accumulation of Cd in leaf tissue, inhibition of the PS II activity, reduced nutrients translocation, and also to the oxidative stress as evidenced by enhanced hydrogen peroxide (H2O2) generation, ion leakage, and lipid peroxidation. AM inoculation significantly enhanced the metal concentration in shoots and reduced growth and yield. The Ikram/Maxifort combination induced higher antioxidant enzymes, higher accumulation of proline and reduction of lipid peroxidation products. This suggests that the use of Maxifort rootstock in tomato has a high reactive oxygen species scavenging activity since lower H2O2 concentrations were observed in the presence of Cd. The higher crop performance of Ikram/Maxifort in comparison to Ikram/Ikram combination was also due to the improved nutritional status (higher P, K, Ca, Fe, Mn, and Zn) and increased availability of metabolites involved in cadmium tolerance (phytochelatin PC2, fructans, and inulins). The up-regulation of LeNRAMP3 gene in leaf of Ikram/Maxifort could explain the better nutritional status of interspecific grafting combination (higher Fe, Mn, and Zn).


Evaluation of USP apparatus 3 for dissolution testing of immediate-release products.
We sought to evaluate whether U.S. Pharmacopeia (USP) apparatus 3 can be used as an alternative to USP apparatus 2 for dissolution testing of immediate-release (IR) dosage forms. Highly soluble drugs, metoprolol and ranitidine, and poorly soluble drugs, acyclovir and furosemide, were chosen as model drugs. The dissolution profiles of both innovator and generic IR products were determined using USP apparatus 2 at 50 rpm and apparatus 3 at 5, 15, and 25 dips per minute (dpm). The dissolution profiles from USP apparatus 3 were compared to those from USP apparatus 2 using the f(2) similarity test. The dissolution profile from USP apparatus 3 generally depends on the agitation rate, with a faster agitation rate producing a faster dissolution rate. It was found that USP apparatus 3 at the extreme low end of the possible agitation range, such as 5 dpm, gave hydrodynamic conditions equivalent to USP apparatus 2 at 50 rpm. With appropriate agitation rate, USP apparatus 3 can produce similar dissolution profiles to USP apparatus 2 or distinguish dissolution characteristics for the IR products of metoprolol, ranitidine, and acyclovir. Incomplete dissolution was observed for the furosemide tablets using USP apparatus 3. Although it is primarily designed for the release testing of extended-release products, USP apparatus 3 may be used for the dissolution testing of IR products of highly soluble drugs, such as metoprolol and ranitidine, and some IR products of poorly soluble drugs, such as acyclovir. USP apparatus 3 offers the advantages of avoiding cone formation and mimicking the changes in physiochemical conditions and mechanical forces experienced by products in the gastrointestinal tract.


Reduced Susceptibility to Rifampicin and Resistance to Multiple Antimicrobial Agents among Brucella abortus Isolates from Cattle in Brazil.
This study aimed to determine the susceptibility profile of Brazilian Brucella abortus isolates from cattle to eight antimicrobial agents that are recommended for the treatment of human brucellosis and to correlate the susceptibility patterns with origin, biotype and MLVA16-genotype of the strains. Screening of 147 B. abortus strains showed 100% sensitivity to doxycycline and ofloxacin, one (0.68%) strain resistant to ciprofloxacin, two strains (1.36%) resistant to streptomycin, two strains (1.36%) resistant to trimethoprim-sulfamethoxazole and five strains (3.40%) resistant to gentamicin. For rifampicin, three strains (2.04%) were resistant and 54 strains (36.73%) showed reduced sensitivity. Two strains were considered multidrug resistant. In conclusion, the majority of B. abortus strains isolated from cattle in Brazil were sensitive to the antimicrobials commonly used for the treatment of human brucellosis; however, a considerable proportion of strains showed reduced susceptibility to rifampicin and two strains were considered multidrug resistant. Moreover, there was no correlation among the drug susceptibility pattern, origin, biotype and MLVA16-genotypes of these strains.


c-erbB-2, p53 protein expression and steroid hormone receptors in breast carcinomas: an immunohistochemical study.
p53, c-erbB-2 protein, steroid hormone receptors, and their correlation with clinicopathologic features were investigated in 70 primary breast carcinomas. All markers were measured immunohistochemically on paraffin sections. Altered p53 expression was found in 27.1% of cases and was associated with negative estrogen receptor status. p53 immunostaining was correlated weakly with histologically lymphatic vessel invasion of carcinoma. c-erbB-2 protein overexpression was seen in 48.6% of cases. A trend was observed in the correlation between c-erbB-2 immunostaining and regional lymph node metastases. Estrogen receptor status was not associated with any histologic or clinical parameters, whereas progesterone receptor status was associated with lymph node metastasis and histologically lymphatic vessel invasion of cancer. PgR status, p53 and c-erbB-2 immunostaining may prove to be an additional criterion in histologic diagnosis of breast cancer.


Prostaglandin effects in the neuroendocrine mammalian brain.
Various prostaglandins (PGs) have been found in several areas of the brain. PGs of the E series have been found in the pituitary and pineal glands and the median eminence, and they have been shown to influence hypothalamic endocrine-release characteristics and release of melatonin from the pineal gland. It has been suggested that they may act, along with membrane phospholipids, as a link between neuronal depolarization, calcium uptake and neurotransmitter release. They may also influence postsynaptic effects of neurotransmitters. These latter effects may be due to interaction with membrane phospholipid- and cyclic nucleotide-induced changes of specific protein kinases. The PGs may act as intracellular mediators of neuro-endocrine control.


Terpenes from Juniperus przewalskii and their antitumor activities.
Two new diterpenes were isolated from Juniperus przewalskii, together with 17 known terpense. Their structures were elucidated by spectroscopic methods (IR, MS, 1H, 13C and 2DNMR). In addition, 3 alpha-hinokiol (3) and 3 alpha-hydroxymannol (9) exhibited effective antitumor activities to cervical carcinoma (HeLa) and human ovarian carcinoma (HO-8910) cell lines.


Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new hope to AML.
In 2017, 4 drugs received US Food and Drug Administration marketing approval for acute myeloid leukemia (AML) treatment: targeted therapies for mutant FLT3 and IDH2, a liposomal cytarabine-daunorubicin formulation for therapy-related AML and AML with myelodysplasia-related changes, and resurgence of an antibody-drug conjugate designed to target CD33. Promising results also emerged for the BCL-2 inhibitor venetoclax combined with low-intensity therapy in older patients unfit for intensive chemotherapy. This quintet of new drugs is likely to reshape the therapeutic landscape of AML.


Hyssopus Essential Oil: An Update of Its Phytochemistry, Biological Activities, and Safety Profile.
The genus Hyssopus is widespread in central Asia, East Mediterranean, and Mongolian areas. It has six main species which are used as herbal remedies, such as Hyssopus officinalis which is used as a condiment and flavoring agent in food industry. The other five species are H. ambiguus, H. cuspidatus, H. latilabiatus, H. macranthus, and H. seravschanicus. Its species are used in the treatment of various ailments such as cold, cough, loss of appetite, fungal infection, and spasmodic condition. Its constituents especially essential oils are popularly used as an additive in beverages, foods, and cosmetics. The volatile constituents are used for aroma in the food industry, cosmetic industry, and household products. The important active constituents in its essential oils are β-pinene, pinocamphone, isopinocamphone, and other terpenoids. Hyssopus genus is also bundled with other secondary metabolites including flavonoids luteolin, quercetin, apigenin, and their glucosides, as well as phenolic compounds including ferulic, p-hydroxy-benzoic acid, protocatechuic acid, chlorogenic, and caffeic acid. Combinedly, the extracts of Hyssopus are reported to have potential antiviral and antifungal activities proven using in vitro studies, whereas in vivo investigations have reported the crucial role of Hyssopus extracts in plasma membrane relaxation, cytotoxic, and sedative effects. This plant is believed to be relatively safe at levels commonly used in foods; nevertheless, more studies are needed to determine the safety profile.


Dietary Alkali-stable Neutral Lipids from Sake Lees Suppress the Formation of Colon Aberrant Crypt Foci in Mice.
We have previously reported that dietary glucosylceramide (GlcCer) and rice extracts containing GlcCer reduce the formation of aberrant crypt foci (ACF) in the colons of 1,2-dimethylhydrazine (DMH)-treated mice, as a precursor model of colon cancer. This study investigated the impact of alkali-stable neutral lipids (NLs) containing free ceramides (Cer) and sterols on the formation of ACF in mice for the purpose of searching for functional components, irrespective of GlcCer, in rice extracts. The fraction was prepared from sake lees as a rice fermentation byproduct. Dietary NLs suppressed the marked increase in colon ACF treated with DMH.


Role of Perceived Competence and Task Interest in Learning From Negative Feedback.
We used functional magnetic resonance imaging to examine the interactive effects of perceived competence and task interest on the cognitive and affective responses to negative feedback. Twenty-four undergraduates performed both interesting and uninteresting tasks and received failure feedback. The participants' perceived competence in the task was manipulated between subjects prior to scanning with bogus feedback. The results showed that negative feedback processing was contingent upon both perceived competence and task interest. The most adaptive coping mechanism, indicated by activation in the cognitive control network and attenuation in the negative affect region, was identified for the high-competence and high-interest combination. When either competence or interest was low, signals in the cognitive control network were weaker. The most detrimental activation patterns were observed for the combination of low-competence and high interest. Our results reveal the combination of task and learner characteristics that best harnesses the potential benefits of negative feedback and illustrate the neuroscientific mechanisms underlying this observation.


Sjögren-Larsson syndrome: a case report and literature review.
Sjögren-Larsson syndrome (SLS) is an autosomal recessive neurocutaneous disorder most commonly seen in the Scandinavian population and characterized by congenital ichthyosis, mental retardation, and spastic diplegia or quadriplegia. We report a case of SLS in an 11-month-old girl of Lebanese and Mexican-Syrian ancestry who presented with ichthyosis, developmental delay, and spasticity. Results of an enzymatic assay and genomic DNA testing in cultured skin fibroblasts confirmed a homozygous C237Y mutation. These findings support the rich diversity of mutations associated with this syndrome.


Malaysian Society of Gastroenterology and Hepatology consensus statement on metabolic dysfunction-associated fatty liver disease.
The Malaysian Society of Gastroenterology and Hepatology saw the need for a consensus statement on metabolic dysfunction-associated fatty liver disease (MAFLD). The consensus panel consisted of experts in the field of gastroenterology/hepatology, endocrinology, bariatric surgery, family medicine, and public health. A modified Delphi process was used to prepare the consensus statements. The panel recognized the high and increasing prevalence of the disease and the consequent anticipated increase in liver-related complications and mortality. Cardiovascular disease is the leading cause of mortality in MAFLD patients; therefore, cardiovascular disease risk assessment and management is important. A simple and clear liver assessment and referral pathway was agreed upon, so that patients with more severe MAFLD can be linked to gastroenterology/hepatology care, while patients with less severe MAFLD can remain in primary care or endocrinology, where they are best managed. Lifestyle intervention is the cornerstone in the management of MAFLD. The panel provided a consensus on the use of statin, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, sodium-glucose cotransporter-2 inhibitor, glucagon-like peptide-1 agonist, pioglitazone, vitamin E, and metformin, as well as recommendations on bariatric surgery, screening for gastroesophageal varices and hepatocellular carcinoma, and liver transplantation in MAFLD patients. Increasing the awareness and knowledge of the various stakeholders on MAFLD and incorporating MAFLD into existing noncommunicable disease-related programs and activities are important steps to tackle the disease. These consensus statements will serve as a guide on MAFLD for clinicians and other stakeholders.


MR imaging of anterior cruciate ligament injuries.
MR imaging has become the imaging modality of choice to evaluate the integrity of the anterior cruciate ligament (ACL). This article discusses the normal anatomy of the ACL and the clinical diagnosis of ACL disruption. The MR imaging appearance of chronic and acute ACL injuries, and the relative value of primary and secondary signs in injury diagnosis are reviewed. The clinical value of MR imaging in the evaluation of the ACL-deficient knee is also discussed.


Organ donation: victory after death.
Despite the Transplantation of Human Organ Act passed in Indian Parliament in 1994, cadaver liver and/or kidney transplant are infrequently performed (in a few private hospitals) in our country compared to living donor liver or kidney transplant. The need for performing more cadaver liver and/or kidney transplants in private and public hospitals is obvious. Immediate measures which should be taken to facilitate more cadaver organ transplant both in private and public hospitals are suggested. Organ donation is for an individual or a family an invaluable opportunity, to register victory after death.


The effect of fat on the coherent-to-Compton scattering ratio in the calcaneus: a computational analysis.
The coherent-to-Compton scattering ratio (CCSR) is a technique that has been proposed for measuring trabecular bone mineral density (TBMD). This paper investigates the effect of fat on the CCSR and its correlation to the error in TBMD measurements. It is a computational study to determine the relationship between the magnitude of fat error and the momentum-transfer variable chi, which represents the incident photon energy and the scattering angle. Variation in fat content contributes significantly to the error in CCSR measurements. When employing a typical 241Am source (E gamma = 59.45 keV), the resulting error decreases with increasing momentum-transfer variable or angle. For example, the error ranges from +14 mg/cc at an angle of 45 degrees (chi = 18.3) to +3 mg/cc at an angle of 135 degrees (chi = 44.3) for an osteoporotic trabecular region (100 mg/cc mineral) of a calcaneus that contains 6% less fat than a calibration standard. The error is about 0.3-1.2 mg/cc less for regions containing 2-3X more bone mineral and is reduced and opposite in sign for regions containing about 7% more fat than the calibration standards (e.g., -9 mg/cc at 45 degrees and -1.5 mg/cc at 135 degrees). Others have shown that the intrinsic sensitivity of the CCSR method for measuring TBMD at a given photon energy generally increases with increasing detector angle. Thus large angles are advantageous both for reduced sensitivity to fat variation and increased sensitivity to bone mineral variation. The primary disadvantage is reduced count rates that degrade precision unless long counting lines are employed.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular analysis of the accessory gene regulator (agr) locus and balance of virulence factor expression in epidemic methicillin-resistant Staphylococcus aureus.
Potential relationships between virulence factor expression and transmissibility were assessed in epidemic methicillin-resistant Staphylococcus aureus (MRSA) clones CMRSA-1 and CMRSA-3. A major subtype of CMRSA-1 exhibited normal transcription of RNAIII, which facilitates the induction of secreted virulence factors and repression of colonization factor expression at high cell density. However, these isolates characteristically did not express alpha-toxin or protease and displayed a limited profile of secreted proteins. CMRSA-1 also expressed a novel cell surface glycoprotein and exhibited a unique polymorphism within the accessory gene regulator (agr) locus. CMRSA-3 displayed attenuated activation of RNAIII transcription, which was consistent with its higher fibronectin-binding and coagulase activity relative to sporadic MRSA or CMRSA-1 (P=.05), low protease activity, and limited profile of secreted proteins. Thus, the balance of virulence factor expression in CMRSA-1 and CMRSA-3 favors the colonization phase of infection, and CMRSA-1 possesses unique genotypic and phenotypic traits.


The Garífuna (Black Carib) people of the Atlantic coasts of Honduras: Population dynamics, structure, and phylogenetic relations inferred from genetic data, migration matrices, and isonymy.
The aim of this study is to assess population dynamics, structure, and phylogenetic relations of the populations that inhabit the Caribbean coasts of Honduras: the Garífuna (or Black Carib) people, an admixture of Black Africans and Red Carib Native Amerindians. Thirteen autosomal tetranucleotide microsatellite markers of the DNA (namely short tandem repeats) were genotyped in samples from the Garifuna communities of Bajamar, in the Department of Cortés; Corozal, in the Department of Atlántida; and Iriona, in the Department of Gracias a Dios. Each subject in the study filled a questionnaire with the following information: complete name and surname of participant, and places of birth of the participant, his/her parents, and grandparents. We performed analyses that included determination of migration rates and residence patterns from information of places of birth, fixation indices from genetic data, and analysis of surnames of the sampled subjects (isonymy). Migration matrices showed a migration wave from east to west in the parents and grandparents of the subjects. A raise in migration rates and a shift in predominating residence pattern from neolocality to matrilocality from grandparents to parents were observed. Analysis of isonymy conjunctly with values for F(IS) in each community showed high endogamy in Bajamar, and recent, high immigration in Iriona. A dendrogram constructed with allele frequencies of the Garifuna and other populations from the Americas, Africa, and Europe revealed the close relationships of this ethnic group with Afro-Caribbean and African Populations.


Laparoscopic live donor nephrectomy at a community hospital.
Recently, laparoscopic harvesting of kidneys from live donors has been reported by major university centers. As a community transplant center, we adopted a multidisciplinary cooperative approach, including a full-time transplant surgeon, a laparoscopic general surgeon, and a urologist with laparoscopic experience, in order to perform our first successful laparoscopic live donor nephrectomy in December 1998. The operative time was 234 minutes, and the warm ischemia time was 2 minutes. No intraoperative or postoperative complications occurred. The length of the renal artery was 2.4 cm, the renal vein was 3.0 cm, and the ureter was 10.0 cm. The donor was discharged home the next day and returned to work within 14 days. The transplanted kidney functioned immediately. The recipient serum creatinine concentration dropped from 9.3 mg/dL preoperatively to 3.4 mg/dL within 24 hours and to 1.3 mg/dL on the third day.


Carotid artery reconstruction for infected carotid patches.
Infected carotid prosthetic patches (ICPP) are a rare but catastrophic complication of carotid endarterectomy (CEA). Prevention and appropriate surgical management is essential. We report our experience of carotid artery reconstruction for ICPP. Single-center retrospective study. 10-year review of the surgical treatment of ICPP. Twelve patients presented with patch infection following CEA. Three patients presented acutely with an expanding hematoma, eight with chronic complications (abscess/discharging sinus n = 5, carotid pseudoaneurysm n = 3). Mean age was 75 years. Replacement conduits included superficial femoral artery (n = 6), cadaveric homograft (n = 3), long saphenous vein (n = 2) and one patient had primary closure. Five patients had muscle flaps fashioned for carotid artery protection. Operative complications included hypoglossal nerve injury (1 patient), superficial skin infection (2 patients) and one patient was returned to the operating room for a neck haematoma. Five surgical specimens were culture positive for: Staphylococcus aureus (n = 3), Corynebacterium propionibacterium (n = 1) and Streptococcus anginous (n = 1). There were no 30-day mortalities. Mean hospital stay was 6 days. Median follow-up was 16 months (range 3-108 months). Carotid artery reconstruction in a contaminated wound represents a significant surgical challenge. Unlike previous reports that used venous conduits, this is the first series where cadaveric or autologous arterial conduits were preferred. Arterial conduits achieved durable short term follow-up.


[Knowledge and practice on schistosomiasis control of boatmen along Yangtze River].
To understand the knowledge and practice on schistosomiasis control of boatmen along the Yangtze River, so as to provide the evidence for making up schistosomiasis control measures for them. In the anchor spots along the Yangtze River in Xinbei District, Changzhou City, a questionnaire survey was carried out for boatmen's knowledge and practice on schistosomiasis control. Among the boatmen of different genders, ages and education levels, the awareness rates of schistosomiasis control knowledge and the formation rates of correct behavior were compared. A total of 702 boatmen of 231 boats were surveyed. The total awareness rate of schistosomiasis control knowledge was 84.19%. Among the groups with different education levels, the awareness rates were significantly different (chi2 =14.42, P < 0.05). The total formation rate of correct behavior on schistosomiasis control was 43.16%. Between men and women groups, and among groups with different ages, the formation rates were significantly different (chi2 = 21.95, 15.00, P < 0.05 for all). Totally 94.81% of the boats discharged the excrement into water directly. The formation rate of correct behavior on schistosomiasis control of boatmen was low, thus the health promotion should be enhanced for them.


The BRASH syndrome, a synergistic arrhythmia phenomenon.
BRASH syndrome is a relatively novel clinical entity with profound bradycardia secondary to simultaneous metabolic derangement and drug toxicity. The syndrome is a clinical pentad of bradycardia, acute kidney injury, use of atrioventricular nodal blocking agents, shock, and hyperkalemia. It is widely underrecognized with selectively few reports, mainly in the elderly population. We present a 43-year-old woman on two oral atrioventricular blocking agents who presented with 1 week of increasing lethargy with rapid deterioration into cardiac arrest with subsequent shock postresuscitation. She was found to have hyperkalemia, metabolic acidosis, and acute kidney injury on arrival. Her initial electrocardiogram was remarkable for sinus arrest and junctional bradycardia. She was treated with a temporary pacemaker, renal replacement therapy, and potassium-lowering agents, with subsequent improvement resulting in conversion to normal sinus rhythm.


Ancient DNA from Polynesian rats: extraction, amplification and sequence from single small bones.
The human colonisation of Polynesia was a major event in world prehistory. It represents one of the last human population migrations, and one which required crossing major water barriers. Though the subject of Pacific population origins has been approached by scholars from numerous fields for nearly a century, recent years have seen the problem addressed by human geneticists. Since the initial report describing the recovery of DNA from skeletal remains, ancient DNA studies have also focused on the Pacific region. In this paper we present the results of ancient DNA analyses of Rattus exulans, an animal that was transported by ancestral Polynesians through the Pacific to the far reaches of the Polynesian triangle. Analysis of DNA of R. exulans skeletal remains has many advantages over studies of ancient human remains, yet the one drawback has been the recovery of ancient DNA from single bones of these very small rodents. We have successfully modified standard extraction protocols for ancient DNA and have consistently extracted, amplified and sequenced mitochondrial DNA (mtDNA) from less than 0.1 g of R. exulans bone and tooth samples recovered from archaeological sites throughout the Pacific, ranging from 400 to 2000 years old.


Myopathy in systemic sclerosis.
Systemic sclerosis associated myopathy (SSc-AM) is a complex, heterogenous disease that is associated with poor outcomes. SSc-AM lacks a clear definition, and continues to be poorly recognized. The purpose of this review is to provide a contemporary overview of the clinical, serological and pathophysiologic findings in SSc-AM to guide optimal recognition and management of this challenging disease manifestation. There have been several advances in diagnostic techniques to facilitate characterization of SSc-AM, including muscle MRI, in which findings were correlated to distinct histopathologic categories of muscle involvement in SSc, histopathologic findings of prominent fibrosis or inflammation on biopsy, and the identification of novel autoantibodies associated with SSc-AM, which may be associated with distinct clinical phenotypes. In one of the largest studies to date, 17% of a well phenotyped SSc cohort were found to have myopathy, which was an independent risk of death, even after adjusting for potential confounders, further highlighting the importance of timely recognistion and management of SSc-AM. There is increasing recognition of the importance of SSc-AM. Novel diagnostic tools provide the opportunity for more detailed insights into pathophysiologic mechanisms, which may facilitate the development of a rigorous consensus definition of SSc-AM.


Current Understanding of Exosomal MicroRNAs in Glioma Immune Regulation and Therapeutic Responses.
Exosomes, the small extracellular vesicles, are released by multiple cell types, including tumor cells, and represent a novel avenue for intercellular communication via transferring diverse biomolecules. Recently, microRNAs (miRNAs) were demonstrated to be enclosed in exosomes and therefore was protected from degradation. Such exosomal miRNAs can be transmitted to recipient cells where they could regulate multiple cancer-associated biological processes. Accumulative evidence suggests that exosomal miRNAs serve essential roles in modifying the glioma immune microenvironment and potentially affecting the malignant behaviors and therapeutic responses. As exosomal miRNAs are detectable in almost all kinds of biofluids and correlated with clinicopathological characteristics of glioma, they might be served as promising biomarkers for gliomas. We reviewed the novel findings regarding the biological functions of exosomal miRNAs during glioma pathogenesis and immune regulation. Furthermore, we elaborated on their potential clinical applications as biomarkers in glioma diagnosis, prognosis and treatment response prediction. Finally, we summarized the accessible databases that can be employed for exosome-associated miRNAs identification and functional exploration of cancers, including glioma.


Novel tretinoin formulations: a drug-in-cyclodextrin-in-liposome approach.
The aims of this experimental work were the incorporation and full characterization of the system Tretinoin-in-dimethyl-beta-cyclodextrin-in-ultradeformable vesicles (Tretinoin-CyD-UDV) and Tretinoin-in-ultradeformable vesicles (Tretinoin-UDV). The Tretinoin-CyD complex was prepared by kneading and the UDV by adding soybean phosphatidylcholine (SPC) to Tween® 80 followed by an appropriate volume of sodium phosphate buffer solution to make a 10%-20% lipid suspension. The resulting suspension was brought to the final mean vesicles size, of approximately 150 nm, by sequential filtration. The physicochemical characterization was based on: the evaluation of mean particle size and polydispersity index (PI) measured by photon correlation spectroscopy (PCS) and atomic force microscopy (AFM) topographic imaging; zeta potential (ζ-potential) and the SPC concentration determined by Laser-Doppler anemometry and an enzymatic-colorimetric test, respectively. The quantification of the incorporated Tretinoin and its chemical stability (during preparation and storage) was assayed by a HPLC at 342 nm. It was possible to obtain the system Tretinoin-CyD-UDV. The mean vesicle size was the most stable parameter during experiments time course. AFM showed that Tretinoin-CyD-UDV samples were very heterogeneous in size, having three distinct subpopulations, while Tretinoin-UDV samples had only one homogeneous size population. The results of the ζ-potential measurements have shown that vesicle surface charge was low, as expected, presenting negative values. The incorporation efficiency was high, and no significant differences between Tretinoin-CyD-UDV and Tretinoin-UDV were observed. However, only Tretinoin-UDV with 20% lipid concentration formulation remained chemically stable during the evaluation period. According to our results, Tretinoin-UDV with 20% lipid concentration seems to be a better approach than Tretinoin-CyD-UDV, attending to the higher chemical stability.


Molecular variants of human papillomavirus type 16 and risk for cervical neoplasia in South Africa.
Non-European variants of human papillomavirus (HPV) type 16 are generally associated with a greater risk of cervical neoplasia than European prototype variants. We investigated whether this association would persist in a population in which non-European HPV 16 variants were more common. We sequenced HPV 16 isolates in cervical samples collected from 93 Black South African women enrolled in a cervical cancer screening study and examined associations between cervical neoplasia identified though colposcopy with cervical biopsy and the specific HPV 16 variant identified. The European prototype variant (EP) was the most commonly identified variant in this population (47% of all isolates), but African variants (Af-1 and Af-2) were also quite common (41% of all isolates). In contrast to previous studies, we found no evidence that non-European variants were associated with an increased risk of neoplasia. Rather, most of the HPV 16-associated cancers were found in association with EP (71% of 14 cases). In this setting where African HPV 16 variants were common, no increased risk for cervical neoplasia was found among women with these variants compared with other HPV 16 variants.


Axillary reverse mapping using 99mTc-SC: a case illustration.
Lymphedema is a common complication in breast carcinoma patients undergoing axillary lymph node dissection. Although there is a significant reduction in the lymphedema rate with sentinel lymph node biopsy compared to axillary lymph node dissection, there is some risk after sentinel lymph node biopsy. Axillary reverse mapping, an emerging concept aims at identifying and preserving the draining lymph node of the arm that is invariably devoid of malignancy. This concept if validated may prevent lymphedema in breast carcinoma patients. Axillary reverse mapping node can be identified using a radiotracer or blue dye. We describe the procedure using filtered Tc-SC.


Multiple epulides in 13 cats.
Epulides account for 0-7.8% of tumors in surveys of feline oral neoplasms. A review of the literature revealed no reports of multiple epulides in cats. Multiple, concurrent epulides were diagnosed microscopically in 13 cats. Fibromatous and ossifying epulides were diagnosed in 11 of 13 cats and fibromatous epulides were diagnosed in 2 of 13 cats. Microscopically, these epulides were nonencapsulated, well-vascularized, infiltrative, highly cellular neoplasms that expanded the gingiva and were composed of haphazardly arranged, spindle-shaped to stellate cells amid a dense, collagenous stroma. Osseous foci were a feature in the fibromatous and ossifying epulides. The mitotic rate was low and there was marked hyperplasia of the overlying gingiva with a prominent downgrowth of epithelial cords. These tumors recurred in 8 of 13 cats following surgical excision. While uncommon, multiple epulides in cats have a high incidence of recurrence but do not appear to have metastatic potential.


Natural history of juvenile haemochromatosis.
Juvenile haemochromatosis or haemochromatosis type 2 is a rare autosomal recessive disorder which causes iron overload at a young age, affects both sexes equally and is characterized by a prevalence of hypogonadism and cardiopathy. Patients with haemochromatosis type 2 have been reported in different ethnic groups. Linkage to chromosome 1q has been established recently, but the gene remains unknown. We report the analysis of the phenotype of 29 patients from 20 families of different ethnic origin with a juvenile 1q-associated disease. We also compared the clinical expression of 26 juvenile haemochromatosis patients with that of 93 C282Y homozygous males and of 11 subjects with haemochromatosis type 3. Patients with haemochromatosis type 2 were statistically younger at presentation and had a more severe iron burden than C282Y homozygotes and haemochromatosis type 3 patients. They were more frequently affected by cardiopathy, hypogonadism and reduced glucose tolerance. In contrast cirrhosis was not statistically different among the three groups. These data suggest that the rapid iron accumulation in haemochromatosis type 2 causes preferential tissue damage. Our results clarify the natural history of the disease and are compatible with the hypothesis that the HFE2 gene has greater influence on iron absorption than other haemochromatosis-associated genes.


Mental health emergencies.
I gained experience of psychiatric assessment in previous roles when working in a secure psychiatric ward and within the prison service. Although I have often performed mental state assessments and assessments of suicidal intent as part of my work, I read the CPD article to refresh my knowledge in this area.


Ocular myasthenia gravis and Graves disease in a 10-year-old child.
We report the association between myasthenia gravis and Graves disease in a 10-year-old boy and discuss the important aspects of both diseases, the importance of recognizing the association, and the investigations of choice to distinguish the 2 disorders. Early diagnosis of the 2 disorders may help in effective treatment institution with more rapid treatment responses with a possible improvement in prognosis and clinical course. Resolution of myasthenia gravis is not expected until the euthyroid state is restored. We recommend complete thyroid status review on all patients presenting with ocular myasthenia gravis.


Influence of Glycine Betaine (Natural and Synthetic) on Growth, Metabolism and Yield Production of Drought-Stressed Maize (Zea mays L.) Plants.
A study was carried out to evaluate the effectiveness of sugar beet extract (SBE) and glycine betaine (GB) in mitigating the adverse effects of drought stress on two maize cultivars. Seeds (caryopses) of two maize cultivars, Sadaf (drought-tolerant) and Sultan (drought-sensitive) were sown in plastic pots. Plants were subjected to different (100%, 75% and 60% field capacity (FC)) water regimes. Then, different levels of SBE (3% and 4%) and GB (3.65 and 3.84 g/L) were applied as a foliar spray after 30 days of water deficit stress. Drought stress significantly decreased plant growth and yield attributes, chlorophyll pigments, while it increased relative membrane permeability (RMP), levels of osmolytes (GB and proline), malondialdehyde (MDA), total phenolics and ascorbic acid as well as the activities of superoxide dismutase (SOD) and peroxidase (POD) enzymes in both maize cultivars. Exogenous application via foliar spray with SBR or GB improved plant growth and yield attributes, chlorophyll pigments, osmolyte concentration, total phenolics, ascorbic acid and the activities of reactive oxygen species (ROS) scavenging enzymes (SOD, POD and catalase; CAT), but reduced leaf RMP and MDA concentration. The results obtained in this study exhibit the role of foliar-applied biostimulants (natural and synthetic compounds) in enhancing the growth and yield of maize cultivars by upregulating the oxidative defense system and osmoprotectant accumulation under water deficit conditions.


Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics.
Signature HIV-1 integrase mutations associated with clinical raltegravir resistance involve 1 of 3 primary genetic pathways, Y143C/R, Q148H/K/R and N155H, the latter 2 of which confer cross-resistance to elvitegravir. In accord with clinical findings, in vitro drug resistance profiling studies with wild-type and site-directed integrase mutant viruses have shown significant fold increases in raltegravir and elvitegravir resistance for the specified viral mutants relative to wild-type HIV-1. Dolutegravir, in contrast, has demonstrated clinical efficacy in subjects failing raltegravir therapy due to integrase mutations at Y143, Q148 or N155, which is consistent with its distinct in vitro resistance profile as dolutegravir's antiviral activity against these viral mutants is equivalent to its activity against wild-type HIV-1. Kinetic studies of inhibitor dissociation from wild-type and mutant integrase-viral DNA complexes have shown that dolutegravir also has a distinct off-rate profile with dissociative half-lives substantially longer than those of raltegravir and elvitegravir, suggesting that dolutegravir's prolonged binding may be an important contributing factor to its distinct resistance profile. To provide a structural rationale for these observations, we constructed several molecular models of wild-type and clinically relevant mutant HIV-1 integrase enzymes in complex with viral DNA and dolutegravir, raltegravir or elvitegravir. Here, we discuss our structural models and the posited effects that the integrase mutations and the structural and electronic properties of the integrase inhibitors may have on the catalytic pocket and inhibitor binding and, consequently, on antiviral potency in vitro and in the clinic.


Dental continuing professional development - Part II: The Malta CPD Pilot Project.
Continuing professional development (CPD) remains voluntary in nine European countries. Evidence suggests a move towards mandatory CPD across Europe with the objective of harmonisation of dental CPD. Although the importance of CPD is acknowledged, the literature regarding its effectiveness is limited and under debate. The main aim was to measure the effectiveness and success of a new CPD programme with the objective to devise a strategy, guidelines and recommendations for the establishment of a dental CPD programme in Malta. This project was divided into two phases; Phase 1 was the analysis of a survey sent out to 135 members of the Dental Association of Malta. Phase 2 involved the evaluation of eight verifiable CPD events, through pre-event and post-event tests and feedback forms, to investigate the effect on short-term knowledge retention and the respective satisfaction levels of participants at each event. The survey had a response rate of 78%. The CPD events in Phase 2 all showed statistically significant improvement in short-term knowledge retention on each subject (p < 0.05). Satisfaction levels ranged from 70% to 99%. The information gathered from this project was used to provide guidelines and recommendations for the local regulatory body and CPD providers for the set-up of a dental CPD framework and programmes in Malta, a country where dental CPD is still voluntary. This article is the second article from a two-part series of articles about the Malta Dental CPD Pilot project.


Survival of patients with HTLV-I-associated lymph node lesions.
Adult T-cell leukaemia/lymphoma (ATLL), is a malignant condition associated with human T-cell leukaemia virus type I (HTLV-I). Usually, although not uniformly, histopathological examination of the lymph nodes shows a pleomorphic type. In addition, some patients with pre-overt ATLL show a Hodgkin's disease-like morphology and lymph nodes in non-neoplastic carriers show features of lymphadenitis. To characterize further the clinicopathological features of HTLV-I-associated lymphadenopathy, the histopathological features of the lymph nodes of 289 patients were classified into five types: lymphadenitis ( n=14), Hodgkin's-like (Hodgkin's) ( n=18), pleomorphic (medium and large cells) ( n=219), pleomorphic small cell ( n=11), and anaplastic large cell (ALC) ( n=27). Survival data were analysed according to the histopathological features of the lymph nodes. The pleomorphic type, which showed typical features of ATLL, was associated with a highly aggressive course and an initially high mortality, followed by a rapid decrease in survival. This pattern was also observed in patients with the ALC type. All cases with lymphadenitis were still alive at the end of the study, while survival progressively decreased in the Hodgkin's type. The small cell type showed an initial rapid decrease in survival followed by a plateau. These results show that the survival trends of patients with pleomorphic and anaplastic lymph node lesions are similar to those with ATL lymphoma, while patients with the lymphadenitis type of lesion were considered to have a non-neoplatic status. There is at present no effective therapy for ATLL, but in the future, these classification and survival data might be useful for the selection of appropriate chemotherapeutic regimens for patients with ATLL.


Hierarchical Particle-In-Quasicavity Architecture for Ultratrace In Situ Raman Sensing and Its Application in Real-Time Monitoring of Toxic Pollutants.
Unstable detection environment is one of the biggest interferences for in situ surface-enhanced Raman spectroscopy (SERS) using in real-time monitoring of toxic pollutants, leading to unreliable results. To address this problem, we have designed and prepared a cavity-based particle-in-quasicavity (PIQC) architecture composed of hierarchical ZnO/Ag nanosheets and nanoprotrusions for improving the in situ SERS performance under a liquid environment. Benefitting from the special cascaded optical field mode, the PIQC ZnO/Ag exhibits excellent in situ SERS detectability, with 10-18 M of limit of detection for rhodamine 6G and 12.8% of signal relative standard deviation value. Furthermore, by means of a microfluidic chip, this PIQC structure is proved to have the quantitative analysis feasibility and realizes real-time monitoring of the 3,3',4,4'-tetrachlorobiphenyl, a representative global environmental hazard, under the flowing environment. The strategy in this paper provides a brand new idea to promote the application of in situ SERS in contaminant monitoring and is also instructive for light control in other optical fields.


Accelerated generation of CD14+ monocyte-lineage cells from the bone marrow of rheumatoid arthritis patients.
To examine the capacity of bone marrow progenitor cells to generate CD14+ cells, in order to assess the role of bone marrow in the pathogenesis of rheumatoid arthritis (RA). CD14- cells purified from bone marrow specimens of 11 patients with active RA and 8 control patients (osteoarthritis or trauma) were cultured in the presence or absence of granulocyte-macrophage colony-stimulating factor (GM-CSF; 100 pg/ml). After incubation for various lengths of time, the cells were analyzed by flow cytometry for expression of CD14 and HLA-DR. The spontaneous generation of CD14+ cells from bone marrow CD14- progenitor cells was accelerated in RA patients compared with control patients. Moreover, the expression of HLA-DR on the bone marrow-derived CD14+ cells was also accelerated in RA patients compared with controls. GM-CSF significantly enhanced the generation of CD14+ cells, as well as the expression of HLA-DR, on CD14+ cells of control patients, but not those of RA patients. GM-CSF levels in the culture supernatants of bone marrow CD14- cells were not significantly different between RA patients and control patients (undetectable in most cases). These observations strongly support the hypothesis that the accelerated generation of CD14+ cells from bone marrow progenitor cells and the accelerated maturation of such CD14+ cells into HLA-DR+ cells play an important role in the pathogenesis of RA. Moreover, the data suggest a functional alteration of RA bone marrow CD14- cells in their responsiveness to GM-CSF.


[Research Progress in Glucose Metabolism of Chondrocytes].
Chondrocytes have a limited supply of glucose and oxygen for metabolism since articular cartilages are relatively avascular. We herein reviewed the characteristics of chondrocyte glucose metabolism and the new research progress in chondrocyte glucose metabolism in the osteoarthritis process. Current research has shown that chondrocytes obtain glucose from synovial fluids and subchondral bones, take in glucose via specific glucose transporters, and metabolize glucose mainly through glycolysis and mitochondrial respiration to produce adenosine triphosphate (ATP). Glucose metabolism in chondrocytes is distinctive because it relies much more on glycolysis rather than mitochondrial respiration for ATP production, and shows Warburg effect and Crabtree effect. In osteoarthritic chondrocytes, the glucose metabolism disorder is presented as further suppression of mitochondrial respiration, over-active or impaired glycolysis, and decreased total production of ATP. However, the significance of the glucose supply for chondrocytes from synovial fluids and subchondral bones remains undefined. There are still disputes in the understanding of the changes in glycolytic pathways in osteoarthritic chondrocytes. Therefore, future research is needed to explore the characteristics of glucose metabolism in normal and osteoarthritic chondrocytes in order to develop new diagnostic and therapeutic strategies for osteoarthritis.


Extinction probability, regularity and asymptotic growth of Markovian populations.
"The distribution of the maximum and the extinction probability for a Markovian population is derived. Asymptotic growth is described, using the sequence of sojourn times. A regularity criterion for the processes under consideration exists under certain assumptions. For a class of processes with specific population-dependent transition rates the asymptotic behaviour is given explicitly."


Molecular mechanism of the activation-induced cell death inhibition mediated by a p70 inhibitory killer cell Ig-like receptor in Jurkat T cells.
In this study we investigated the molecular mechanism of the activation-induced cell death (AICD) inhibition mediated by a p70 inhibitory killer cell Ig-like receptor (KIR3DL1, also called NKB1) in Jurkat T cells. Using stable Jurkat transfectants that express KIR or CD8-KIR fusion proteins we have shown for the first time that KIR inhibits, in a ligation-independent manner, the AICD induced by PHA, PMA/ionomycin, or anti-CD3 Ab. The AICD inhibition mediated by KIR appears to result from the blockade of Fas ligand induction upon activation of the Jurkat transfectants. Moreover, the membrane-proximal 20 aa of the KIR cytoplasmic tail were determined to play a crucial role in this process. Since the membrane-proximal portion of the KIR cytoplasmic tail contains a putative protein kinase C (PKC) substrate site, we investigated the molecular interaction between KIR and PKC. Immunoprecipitation analysis demonstrated that KIR constitutively bound both to PKCalpha, a conventional Ca(2+)-dependent PKC, and to PKCtheta, a novel Ca(2+)-independent PKC. Furthermore, an in vitro kinase assay revealed that PKC activation was blocked after PHA stimulation in Jurkat transfectants expressing KIR. These observations were supported by the finding that a recombinant KIR cytoplasmic tail also appeared to inhibit PKCalpha activation in vitro. Taken together these data strongly suggest that KIR inhibits the AICD of T cells by blocking Fas ligand induction upon stimulation, in a process that seems to be accomplished by PKC recruitment to the membrane-proximal PKC binding site and subsequent inhibition of PKC activation against the activating stimuli.


Cecal volvulus in a child with CHARGE syndrome.
Cecal volvulus occurring in a child with CHARGE syndrome is presented. This boy was known to have CHARGE syndrome with multiple congenital anomalies, including coloboma, ventricular septal defect, choanal atresia, growth and mental retardation, bilateral cryptorchidism, dysplasia of the right ear, cleft lip, and hydrocephalus. Nissen's fundoplication had been previously performed for severe hiatal hernia and gastroesophageal regurgitation at the age of 1 year. Cecal volvulus occurred with a 540-degree clockwise rotation of terminal ileum to the right transverse colon and a displacement of the rotated loop to the right upper quadrant of the abdomen when he was 10 years old. Right hemicolectomy with divided ileo- and colostomy was performed. A second staged ileocolostomy was performed uneventfully 3 months later. The midline structural defects with nonfixation of the cecum and ascending colon, chronic constipation, and previous abdominal surgery might have been the predisposing factors.


Treatment of hepatocellular carcinoma: a systematic review.
Hepatocellular carcinoma (HCC) is one of the most common malignancies, with an increasing incidence. With advances in surgical techniques and instrumentation and the development of molecular-target drugs, a number of potentially curative treatments have become available. Management of HCC patients depends on the stage of their tumor. Liver resection remains the first choice for very early-stage HCC, but it is being challenged by local ablative therapy. For early-stage HCC that meet the Milan criteria, liver transplantation still offers a better outcome; however, local ablative therapy can be a substitute when transplantation is not feasible. Local ablation is also used as a bridging therapy toward liver transplantation. HCC recurrence is the main obstacle to successful treatment, and there is currently no effective means of preventing or treating HCC recurrence. Transarterial therapy is considered suitable for intermediate-stage HCC, while sorafenib is recommended for advanced-stage HCC. This stage-based approach to therapy not only provides acceptable outcomes but also improves the quality of life of HCC patients. Because of the complexity of HCC, therapeutic approaches must be adapted according to the characteristics of each individual patient. This review discusses the current standards and trends in the treatment of HCC.


Factors limiting the hydrolysis of casein by subtilisin DY.
It was shown that during the subtilisin DY-induced hydrolysis of casein relatively stable polypeptide structures are formed. In their interior these structures contain peptide bonds which are susceptible to the enzyme used. Heating (up to 100 degrees C) and/or application of ultrasound (25 kHz, 60 W) results in their unfolding. Data are provided, which show that under the enzyme-substrate complex formation does not lead to an enzyme conformation more susceptible to autolysis. Taking into account the described phenomena a higher degree of hydrolysis was attained in comparison to those obtained by standard enzymatic hydrolysis.


Social Media Outrage in Response to a School-Based Substance Use Survey: Qualitative Analysis.
School-based alcohol, tobacco, and other drug use (ATOD) surveys are a common epidemiological means of understanding youth risk behaviors. They can be used to monitor national trends and provide data, in aggregate, to schools, communities, and states for the purposes of funding allocation, prevention programming, and other supportive infrastructure. However, such surveys sometimes are targeted by public criticism, and even legal action, often in response to a lack of perceived appropriateness. The ubiquity of social media has added the risk of potential online firestorms, or digital outrage events, to the hazards to be considered when administering such a survey. Little research has investigated the influence of online firestorms on public health survey administration, and no research has analyzed the content of such an occurrence. Analyzing this content will facilitate insights as to how practitioners can minimize the risk of generating outrage when conducting such surveys. This study aimed to identify common themes within social media comments comprising an online firestorm that erupted in response to a school-based ATOD survey in order to inform risk-reduction strategies. Data were collected by archiving all public comments made in response to a news study about a school-based ATOD survey that was featured on a common social networking platform. Using the general inductive approach and elements of thematic analysis, two researchers followed a multi-step protocol to clean, categorize, and consolidate data, generating codes for all 207 responses. In total, 133 comments were coded as oppositional to the survey and 74 were coded as supportive. Among the former, comments tended to reflect government-related concerns, conspiratorial or irrational thinking, issues of parental autonomy and privacy, fear of child protective services or police, issues with survey mechanisms, and reasoned disagreement. Among the latter, responses showed that posters perceived the ability to prevent abuse and neglect and support holistic health, surmised that opponents were hiding something, expressed reasoned support, or made factual statements about the survey. Consistent with research on moral outrage and digital firestorms, few comments (<10%) contained factual information about the survey; nearly half of the comments, both supportive and oppositional, were coded in categories that presupposed misinformation. The components of even a small online firestorm targeting a school-based ATOD survey are nuanced and complex. It is likely impossible to be fully insulated against the risk of outrage in response to this type of public health work; however, careful articulation of procedures, anticipating specific concerns, and two-way community-based interaction may reduce risk.


[Recent findings on scleral extracellular matrix and matrix metalloproteinases in the development of myopia].
Myopia is the most common eye disorder worldwide. So far there is no effective treatment for the disease. Recent findings indicated that the remodeling of scleral extracellular matrix (ECM) plays an important role in the development of myopia. The dynamic changes of matrix metalloproteinases in myopia (MMPs) activity, one of the most important enzymes that regulates the ECM, has a significant correlation with myopia. This review gives the latest findings about ECM and MMPs in the development of myopia.


Isolation and chromosomal mapping of a mouse homolog of the Batten disease gene CLN3.
We describe the isolation and chromosomal mapping of a mouse homolog of the Batten disease gene, CLN3. Like its human counterpart, the mouse cDNA contains an open reading frame of 1314 bp encoding a predicted protein product of 438 amino acids. The mouse and human coding regions are 82 and 85% identical at the nucleic acid and amino acid levels, respectively. The mouse gene maps to distal Chromosome 7, in a region containing genes whose homologs are on human chromosome 16p12, where CLN3 maps. Isolation of a mouse CLN3 homolog will facilitate the creation of a mouse model of Batten disease.


Extending urban services in developing countries: policy options and organizational choices.
Governments in developing countries will face serious problems in extending basic social services, public facilities, and infrastructure for their rapidly growing urban populations during the next decade. The steadily increasing concentration of the poor in cities will exacerbate already severe strains on urban services. Innovative solutions will be needed to meet the growing demands for urban services. In addition to expanding national and municipal efforts, governments in developing countries must also explore alternative policies and organizational arrangements for meeting the basic needs of their urban population. Among the potential alternatives are: using market surrogates to improve service delivery; lowering the costs of service provision through changes in regulations and controls on urban development; actively supporting self-help and service upgrading schemes by the poor; promoting public-private cooperation and private sector participation in service delivery; increasing effective demand for services by promoting employment and higher incomes; and enacting and implementing policies that attempt to redistribute migration to small and intermediate-sized cities. Each alternative has advantages and limitations that planners and policy-makers must take into consideration in forging effective urban development strategies.


Sulfate Transport in Cultured Tobacco Cells : EFFECTS OF CALCIUM AND SULFATE CONCENTRATION.
Sulfate transport by tobacco cells (var. Xanthi) cultured in liquid medium was investigated. Monophasic uptake was observed over a sulfate concentration range from 0.01 to 10 millimolar, and the K(m) was 20 micromolar. A time-dependent stimulation of transport was observed when cells were incubated in medium containing 0.5 millimolar Ca(2+). Calcium stimulation was dependent on the culture cycle and was maximal during the early exponential phase. It was not observed in sulfur-deficient cells with high transport rates and was relatively small in sulfate-loaded cells with low transport rates. A kinetic analysis showed that Ca(2+) increased the maximum rate of transport without affecting the K(m).


Targeting AKT protein kinase in gastric cancer.
Gastric cancer is a highly lethal malignancy with more than 700,000 deaths every year worldwide. Despite significant improvements in our understanding of disease biology, the 5-year survival rates remain low. With the exception of trastuzumab, targeted agents have failed to add any meaningful benefit for this patient population, despite promising pre-clinical data. Protein kinase B (AKT) is essential for cell growth, proliferation, and survival. Aberrant activation of AKT is one of the most common molecular findings in human malignancies including gastric cancer, and it is believed to play an important role in cancer cell survival and chemotherapy resistance. Combining phosphatidylinositol 3-kinase (PI3K)/AKT pathway inhibitors with chemotherapy has successfully attenuated chemotherapeutic resistance in gastric cancer cell lines. Drugs designed to specifically target AKT are now being developed for clinical use. In this article, we will review the current knowledge on AKT signaling in the pathogenesis of gastric cancer and the evolving therapeutic implications of targeting this pathway.


An extended approach for the vascular pedicle of the lateral arm free flap.
We present an extension of the surgical approach for harvesting the lateral upper arm free flap by which an additional 6 to 8 cm of pedicle length may be gained. First, the flap is raised by the standard lateral approach. Then, by proceeding proximally and posteriorly, the triceps muscle is split between its lateral and long heads to expose the entire length of the profunda brachii vessels in the spiral groove. A tunnel is developed beneath the lateral head of the triceps, and the flap or its pedicle is delivered through this. We describe the surgical technique and present details of a dissection study on 25 fresh cadaver limbs. The nerve branches to the lateral head of the triceps, which are close to the vessels of the flap, are highly variable in number and location. When unusually short and distally placed, they are at risk of damage, but damage can be avoided if the tunnel is not unduly widened. We present our early clinical experience in 10 consecutive cases using the extended-pedicle lateral arm flap. The free pedicle length in this series ranged from 8 to 13 cm. The maximum flap size was 5 x 19 cm. All cases were successful, although one required reoperation for venous thrombosis. Although postoperative testing of upper arm muscle function showed some weakness and impaired endurance, this was found equally in the surgically disturbed triceps and in the untouched elbow flexors and thus could not be attributed to motor nerve damage to the triceps muscle.


Changes after conservative surgical treatment for early breast carcinoma: comparison of sonographic and bioptic findings.
The aim of the study was evaluation of interventional ultrasound in the diagnostics of changes after conservative surgical treatment for early breast carcinoma and in the therapeutic removal of postoperative seromas. The analysis of USG- and bioptic findings in 240 breast cancer patients after conservative breast surgery performed between 1996-1998 is reported. The major findings were: postoperative scars, granulomas, seromas, hematomas, fat necrosis, skin thickening, inflammatory changes and local tumor recurrence. In our experience, the interventional ultrasound coupled with cytological examination are reliable methods for the follow up of early and late postoperative changes with sufficient degree of correlation between USG- and histologic findings.


Cross-regulation of T cell growth factor expression by p53 and the Tax oncogene.
In this study, we demonstrate that p53 directly inhibits expression of the T cell growth factor (IL-2) in activated T cells. This repression is independent of the intrinsic transcriptional activity of p53 and is mediated by the Tax-responsive CD28RE-3'-12-O-tetradecanoylphorbol-13-acetate response element (AP1) element of the IL-2 promoter. Coexpression of the Tax oncogene causes full reversal of this repression through coordinate targeting of p300, CREB, and the NF-kappaB pathways. Paradoxically, IL-2 repression by p53 is not reversed by mdm2. Instead, mdm2 represses the IL-2 promoter by a mechanism that is synergistic with p53 and resistant to Tax reversal. The p300 structure-function studies show that these effects are linked to competitive associations among p53, Tax, and mdm2 with multiple domains of p300. The functional outcome of these antagonistic associations is revealed further by the observation that Tax and p53 induce apoptosis in activated T cells through separate and mutually exclusive pathways. Interestingly, both pathways are abrogated by mdm2. These results provide evidence that a dynamic interplay, between Tax and specific elements of the p53 network, mediates growth factor expression and programmed cell death in activated T cells.


Investigating word class effects in first and second languages.
According to Zyzik in 2009, only a few recent studies have investigated similarities in use of words in comprehension of first languages (L1) and second languages (L2). Furtner, Rauthmann, and Sachse showed a rank order of word classes by frequency of eye-gaze regression when reading other difficult words: nouns, adjectives, closed-class words, verbs. The hypothesis was that a L1-L2 word-class similarity effect between German (L1) and English (L2) would occur, and this was tested with jumbled word reading of English text (wherein letters within words Shave been jumbled) and eye-tracking by 141 participants. Analyses of regressive fixations from one word class to others showed that nouns were regressed most often and there was a rank order of importance among the word classes apparently used to enhance comprehension of other difficult words (nouns, adjectives, verbs, dosed-class words). Thus, previous findings for L1 were largely replicated. Findings are discussed regarding language acquisition.


Raman Spectroscopic Techniques for Planetary Exploration: Detecting Microorganisms through Minerals.
Raman spectroscopy can provide highly specific chemical fingerprints of inorganic and organic materials and is therefore expected to play a significant role in interplanetary missions, especially for the search for life elsewhere in our solar system. A major challenge will be the unambiguous detection of low levels of biomarkers on a mineral background. In addition, these biomarkers may not be present at the surface but rather inside or underneath minerals. Strong scattering may prevent focusing deeper into the sample. In this paper, we report the detection of carotenoid-containing microorganisms behind mineral layers using time-resolved Raman spectroscopy (TRRS). Two extremophiles, the bacterium Deinococcus radiodurans and the cyanobacterium Chroococcidiopsis, were detected through translucent and transparent minerals using 440 nm excitation under resonance conditions to selectively enhance the detection of carotenoids. Using 3 ps laser pulses and a 250 ps gated intensified CCD camera provided depth selectivity for the subsurface microorganisms over the mineral surface layer and in addition lowered the contribution of the fluorescent background. Raman spectra of both organisms could be detected through 5 mm of translucent calcite or 20 mm of transparent halite. Multilayered mineral samples were used to further test the applied method. A separate tunable laser setup for resonance Raman and a commercial confocal Raman microscope, both with continuous (non-gated) detection, were used for comparison. This study demonstrates the capabilities of TRRS for the depth-selective analysis through scattering samples, which could be used in future planetary exploration to detect microorganisms or biomarkers within or behind minerals.