Elevated serum methylmalonic acid. How much comes from cobalamin deficiency and how much comes from the kidneys?
Serum methylmalonic acid (S-MMA) as a sensitive indicator of cobalamin deficiency was introduced more than 10 years ago. The use of this method for identifying patients with cobalamin deficiency reflects much higher prevalence figures than was previously thought. In this review, all major studies on the subject are analysed. The least common denominator that could explain the probably overrated prevalence figures is the deteriorated renal function accepted for inclusion in virtually all the studies. A strong association between S-MMA and S-creatinine, even within the normal range for creatinine. has become increasingly apparent. At present, it is impossible to estimate how much of elevated S-MMA comes from impaired renal function and how much comes from impaired cobalamin metabolism. Thus, the use of S-MMA as the sole indicator of cobalamin deficiency cannot be recommended.


[Clinical study in prophylactic use of chinese medicine to prevent chemoradiotherapy induced mucositis in nasopharyngeal carcinoma].
Oropharyngeal mucositis is the most common acute non-hematology toxicity in nasopharyngeal carcinoma (NPC) treated with radiotherapy, especially in the concomitant chemoradiotherapy of local advanced NPC patients. This study was designed to observe the effect of traditional Chinese medicine against acute oropharyngeal mucositis from chemoradiotherapy in patients with local advanced NPC. A total of 101 patients in stage III- IVa (Fuzhou 1992) were enrolled into this prospective randomized clinical trial. The cases were divided into treatment group (52 cases) and control group (49 cases). The median doses were 70.31+/-1.21 Gy for the treatment group and 70.78+/-1.95 Gy for the control group, respectively. Chemotherapy was concomitant with radiotherapy [single agent cisplatin (DDP,30 mg/m(2)) 6 times from first to sixth week of radiotherapy duration]. The patients of treatment group took 5-8 times of Chinese medicine daily and those of control group took 5-8 times of Dobell's solution daily.The observation indices included the degree of oropharyngeal and hematological toxicity, radiotherapy duration, and curative effect. (1)Oropharyngeal toxicity: there was no 0 degree oropharyngeal toxicity in both groups, I degree toxicity in 29 cases (55.77%) and 2 cases (4.08%), II degree toxicity in 18 cases (34.62%) and 17 cases (30.69%), III degree toxicity in 5 cases (9.62%) and 22 cases (44.89%), IV degree toxicity in 0 case (0%) and 8 cases (16.33%); there was statistical significance of difference between the two groups (P=0.000). (2)Hematological toxicity: there was no IV degree hematological toxicity in both groups. WBC toxicity (Z=-0.604,P=0.546), neutrophilic granulocyte toxicity (Z=-0.226,P=0.821), and platelet toxicity (Z=-0.099,P=0.922) were compared; there was no statistic significance of difference (P >0.05); (3)Radiotherapy duration: The radiotherapy duration of two groups were 49.79+/-1.83 days and 51.00+/-4.46 days; there was no statistic significance of difference (P=0.082). (4)Curative effects: The curative effects of two groups were:complete remission (CR) 76.92% (40/52) and 69.39% (34/49), partial remission (PR) 23.08% (12/52) and 30.61% (15/49); there was no statistical significance of difference (P=0.392). Chinese medicine was effective in reducing acute oropharyngeal toxicity resulting from chemoradiotherapy in patients with local advanced NPC. Furthermore, the apparent side effects of Chinese medicine in this study have not been observed. Chinese medicine treatment did not affect the short-term clinical outcome.


Monte Carlo studies on photon interactions in radiobiological experiments.
X-ray and γ-ray photons have been widely used for studying radiobiological effects of ionizing radiations. Photons are indirectly ionizing radiations so they need to set in motion electrons (which are a directly ionizing radiation) to perform the ionizations. When the photon dose decreases to below a certain limit, the number of electrons set in motion will become so small that not all cells in an "exposed" cell population can get at least one electron hit. When some cells in a cell population are not hit by a directly ionizing radiation (in other words not irradiated), there will be rescue effect between the irradiated cells and non-irradiated cells, and the resultant radiobiological effect observed for the "exposed" cell population will be different. In the present paper, the mechanisms underlying photon interactions in radiobiological experiments were studied using our developed NRUphoton computer code, which was benchmarked against the MCNP5 code by comparing the photon dose delivered to the cell layer underneath the water medium. The following conclusions were reached: (1) The interaction fractions decreased in the following order: 16O > 12C > 14N > 1H. Bulges in the interaction fractions (versus water medium thickness) were observed, which reflected changes in the energies of the propagating photons due to traversals of different amount of water medium as well as changes in the energy-dependent photon interaction cross-sections. (2) Photoelectric interaction and incoherent scattering dominated for lower-energy (10 keV) and high-energy (100 keV and 1 MeV) incident photons. (3) The fractions of electron ejection from different nuclei were mainly governed by the photoelectric effect cross-sections, and the fractions from the 1s subshell were the largest. (4) The penetration fractions in general decreased with increasing medium thickness, and increased with increasing incident photon energy, the latter being explained by the corresponding reduction in interaction cross-sections. (5) The areas under the angular distribution curves of photons exiting the medium layer and subsequently undergoing interactions within the cell layer became smaller for larger incident photon energies. (6) The number of cells suffering at least one electron hit increased with the administered dose. For larger incident photon energies, the numbers of cells suffering at least one electron hit became smaller, which was attributed to the reduction in the photon interaction cross-section. These results highlighted the importance of the administered dose in radiobiological experiments. In particular, the threshold administered doses at which all cells in the exposed cell array suffered at least one electron hit might provide hints on explaining the intriguing observation that radiation-induced cancers can be statistically detected only above the threshold value of ~100 mSv, and thus on reconciling controversies over the linear no-threshold model.


Subsistence hunting of Cuniculus paca in the middle of the Solimões River, Amazonas, Brazil.
Ungulates, large primates and caviomorfs are cited by Amazonian hunters as preferred species. In this research, paca (Cuniculus paca) hunting was investigated in relation to water levels and the lunar cycle. In eight years of monitoring in the Amanã Sustainable Development Reserve, the killing of 625 pacas was registered in five monitored communities. Paca hunting took place mainly at night and the most commonly used method is "spotlighting". A positive correlation between the number of pacas killed and water level (rs=0.890; p<0.0001) was found. At least 37% of the pacas were hunted when moon illumination level was less than 10%, before moonrise or after moonset. In the Boa Esperança community, capture of paca tended to decrease on nights with high moon illumination (rs= -0.663; p=0.067). At the same time, an expressive catch-per-unity-effort decrease was also observed in this community (r2= -0.881; p<0.001), allowing us to predict unsustainable hunting levels for the next decade. The stock of animals in these areas could be continuously replaced if surrounding areas consisted of continuous forests. However, continuous hunting and deforestation force local hunters to travel longer distances to kill prey such as pacas. The confirmation of the relation between paca habits and lunar illumination and water level, a pattern described by local hunters, demonstrates the potential value of participatory research and the possibility of integrating traditional knowledge into scientific knowledge.


Observations of clustering inside oceanic bubble clouds and the effect on short-range acoustic propagation.
It has recently been shown [Weber, T. C. et al. (2007). "Acoustic propagation through clustered bubble clouds," IEEE J. Ocean. Eng. 32, 513-523] that gas bubble clustering plays a role in determining the acoustic field characteristics of bubbly fluids. In particular, it has been shown that clustering changes the bubble-induced attenuation as well as the ping-to-ping variability in the acoustic field. The degree to which bubble clustering exists in nature, however, is unknown. This paper describes a method for quantifying bubble clustering using a high frequency (400 kHz) multibeam sonar, and reports on observations of near-surface bubble clustering during a storm (14.6 m/s wind speed) in the Gulf of Maine. The multibeam sonar data are analyzed to estimate the pair correlation function, a measure of bubble clustering. In order to account for clustering in the mean acoustic field, a modification to the effective medium wave number is made. With this modification, the multibeam sonar observations are used to predict the effect of clustering on the attenuation of the mean field for short-range propagation (1 m) at frequencies between 10 and 350 kHz. Results for this specific case show that clustering can cause the attenuation to change by 20%-80% over this frequency range.


Structural determination of the polar glycoglycerolipids from thermophilic bacteria Meiothermus taiwanensis.
The polar glycolipids were isolated from the thermophilic bacteria Meiothermus taiwanensis ATCC BAA-400 by ethanol extraction and purified by Sephadex LH-20 and silica gel column chromatography. The fatty acid composition of O-acyl groups in the glycolipids was obtained by gas chromatography mass spectroscopy analysis on their methyl esters derived from methanolysis and was made mainly of C(15:0) (34.0%) and C(17:0) (42.3%) fatty acids, with the majority as branched fatty acids (over 80%). Removal of O-acyl groups under mild basic conditions provided two glycolipids, which differ only in N-acyl substitution on a hexosamine. Electrospray mass spectroscopy analysis revealed that one has a C(17:0) N-acyl group and the other hydroxy C(17:0) in a ratio of about 1 : 3.5. Furthermore, complete de-lipidation with strong base followed by selective N-acetylation resulted in a homogeneous tetraglycosyl glycerol. The linkages and configurations of the carbohydrate moiety were then elucidated by MS and various NMR analyses. Thus, the major glycolipid from M. taiwanensis ATCC BAA-400 was determined with the following structure: alpha-Galp(1-6)-beta-Galp(1-6)-beta-GalNAcyl(1,2)-alpha-Glc(1,1)-Gro diester, where N-acyl is C(17:0) or hydroxy C(17:0) fatty acid and the glycerol esters were mainly iso- and anteisobranched C(15:0) and C(17:0).


Integration sites of human papillomavirus 18 DNA sequences on HeLa cell chromosomes.
Human papillomaviruses (HPV) 16 and 18 are closely linked with human genital cancer. In most cervical carcinomas, viral sequences are integrated into the host genome. HeLa, a cervical carcinoma cell line, has multiple copies of integrated HPV 18 DNA. In this study, in situ chromosome hybridization was used to assign the integration sites of HPV 18 DNA sequences on HeLa cell chromosomes. Four sites of hybridization were identified at 8q23----q24, 9q31----q34, p11----p13 on an abnormal chromosome 5, and q12----q13 on an abnormal 22. Three of these sites correspond with the locations of MYC, ABL, and SIS protooncogenes, and are at or in close proximity to fragile sites. The chromosomal localization of HPV 18 DNA may be useful in assessing the role of viral integration in the development of this malignancy.


Impaction of factors associated with oxidative stress on the pathogenesis of gestational hypertension and preeclampsia: A Chinese patients based study.
We aimed to investigate the effect of Kelch-like ECH-associated protein 1/NF-E2 p45-related factor 2 (Keap1/Nrf2) pathway on the biological function of trophoblast cells in oxidative stress model at the cellular level, and analyzed the expression level and clinical significance of Keap1/Nrf2 pathway and related antioxidant factors in placental tissues of Preeclampsia (PE) patients at clinical level. In present study, we found that under hypoxia/reoxygenation conditions, the activity of oxidative stress-related enzymes (CAT, GSH-Px, SOD) in HTR8/SVneo cells was significantly lower than that before treatment (P < .01). The activities of CAT, GSH-Px and SOD in HTR8/SVneo cells in SiRNA+H/R group decreased significantly (P < .01), indicating the important defense effect of Keap1/Nrf2 signaling pathway in oxidative stress. As a control group of Nrf2 SiRNA+H/R group, Si-NC+H/R group had CAT, GSH-Px and SOD activities decreasing, which was similar to that in H/R group. Moreover, the activities of oxidative stress-related active enzymes in patients with PE were further confirmed by detecting and comparing the activities of CAT, GSH-Px and SOD in placental tissues. The results showed that the activity of SOD (P < .001), GSH-Px (P < .01) and CAT (P < .01) in placental tissues of patients with PE were significant different from those of normal placental tissues. The expression level of Keap1 in placenta of patients with PE was slightly lower than that of normal placenta. While the expression of Nrf2 in placenta of patients with PE was significantly higher than that of normal placenta. HO-1 expression in placenta of patients with PE was significantly higher than that of normal placenta. These results implicate the importance of Keap-1/Nrf2 pathway in PE.


CATION TRANSPORT IN ESCHERICHIA COLI. IV. KINETICS OF NET K UPTAKE.
The resuspension of K-poor, Na-rich stationary phase E. coli in fresh medium at pH 7.0 results in a rapid uptake of K and extrusion of Na by the cells. In all experiments net K uptake exceeded net Na extrusion. An investigation of the uptake of glucose, PO(4), and Mg and the secretion of H by these cells indicates that the excess K uptake is not balanced by the simultaneous uptake of anions but must be accompanied by the extrusion of cations from the cell. The kinetics of net K uptake are consistent with the existence of two parallel influx processes. The first is rapid, of brief duration, and accounts for approximately 60 per cent of the total net K uptake. This process is a function of the extracellular K concentration, is inhibited in acid media, and appears to be a 1 for 1 exchange of extracellular K for intracellular H. The second influx process has a half-time of approximately 12 minutes, and is not affected by acid media. This process is a function of the intracellular Na concentration, is dependent upon the presence of K in the medium, and may be ascribed to a 1 for 1 exchange of extracellular K for intracellular Na.


Regulating Oxygen Redox Chemistry through the Synergistic Effect of Transition-Metal Vacancy and Substitution Element for Layered Oxide Cathodes.
Reversible oxygen redox (OR) is considered as a paradigmatic avenue to boost the energy densities of layered oxide cathodes. However, its activation is largely coupled with the local coordination environment around oxygen, which is usually accompanied with irreversible oxygen release and unfavorable structure distortion. Herein, it is revealed that the synergistic effect of transition-metal (TM) vacancy and substitution element for modulating the OR activity and reversibility of layered Na0.67 MnO2 through multimodal operando synchrotron characterizations and electrochemical investigations. It is disclosed that TM vacancy can not only suppress the complicated phase transition but also stimulate the OR activity by creating nonbonding O 2p states via the Na─O─vacancy configurations. Notably, the substitution element plays a decisive role for regulating the reversibility of vacancy-boosted OR activity: the presence of strong Al─O bonds stabilizes the Mn-O motifs by sharing O with Al in the rigid Mn─O─Al frameworks, which mitigates TM migration and oxygen release induced by TM vacancy, leading to enhanced OR reversibility; while the introduction of weak Zn─O bonds exacerbates TM migration and irreversible oxygen release. This work clarifies the critical role of both TM vacancy and substitution element for regulating the OR chemistry, providing an effective avenue for designing high-performance cathodes employing anionic redox.


[Roentgenological and radiological examination of persons with an increased risk of lung cancer].
The present system of the detection of lung cancer does not provide sufficient efficacy of mass screening. The paper is concerned with the results of the examination of organized population. The following methods were used: questionnaires, large picture frame fluorography, cytological examination of the sputum, radiopulmonography with 133Xe, the determination of carcinoembryonic antigen and thyroid hormones in the blood serum. Altogether two groups were examined: 787 practically healthy persons with a high risk of lung cancer and 193 patients with verified lung cancer. The results obtained were correlated in both groups using various methods. Mass screening should include the isolation of high risk groups and the differentiation of persons by a degree of disease probability. Persons with a high risk of this disease are subjected to regular examination using large picture frame fluorography and cytology of the sputum. Radiopulmonography should be performed as an adjuvant diagnostic procedure to examine persons from high risk groups in the presence of changes on the fluorograms and atypical cells in the sputum.


[Serial Assessment of Transthoracic Coronary Flow Reserve as Method of Assessing Efficacy of Intracoronary Intervention in the Left Anterior and Posterior Descending Arteries].
Transthoracic echocardiography (TTE) has been described as an accurate technique for noninvasive evaluation of coronary flow reserve (CFR) of the left anterior descending artery (LAD) and posterior descending artery (PDA). Aim of this study was to find out whether serial measurement of CFR in LAD and PDA using TTE allows detection of stenosis elimination after intracoronary intervention and is a marker of successful procedure. The study group comprised 14 patients with single-vessel coronary disease (stenosis 82+/-14%) of the LAD (9 patients) or right coronary artery (RCA, 5 patients) scheduled for stent implantation. All patients underwent dipyridamole stress echo with CFR evaluation of either distal LAD or PDA 1 day before and 6-9 days after successful stent implantation. CFR was calculated as the ratio of hyperemic to basal peak diastolic velocity. A CFR value of <2.0 was considered abnormal. Adequate Doppler signals to measure CFR were obtained in 13 patients (93%). Abnormal pre-procedure CFR value was revealed in 12 assessed patients (92%). Significant increase of CFR due to a decrease of coronary flow velocity at rest and its more pronounced hyperemic rise was found in all patients after stent implantation (CFR: 1.28+/-0.52 before and 2.53+/-0.37 after stenting; p<0.001). Using a cut-off value of CFR more or equal 2.0 to identify absence of significant coronary artery disease, TTE detected successful stent implantation with a sensitivity of 91.7% and specificity of 100% for both LAD and RCA. CFR was still abnormal in only 1 patient with pre-procedure>90% LAD stenosis. TTE is a feasible technique for serial CFR evaluation in LAD and PDA. Cut-off CFR value more or equal 2.0 is a sensitive and specific criterion of successful stent implantation in LAD and RCA.


[Effect of nitrates on arterial blood vessels exemplified by the radial artery].
Nitrates act, in part, by causing systemic venodilation. In addition, nitrates lead to dilation of arterial conductance vessels. The maximal dilation capacity and threshold of arterial conductance vessels have so far not been examined thoroughly. Therefore, we tested the radial artery diameter before and after i.v. nitroglycerin infusions at increasing dosages (0.015, 0.05, 0.15, 0.5, and 1.5 micrograms/kg/min), 7 min each dose in 28 patients with suspected coronary artery disease (mean age +/- SEM 58 +/- 2 years) using a high resolution ultrasound devise. The low doses of 0.05 and 0.15 microgram/kg/min, equal to dose of 2.5 mg/12 hours and 7.5 mg/12 hours in a patient with 70 kg, led to substantial increases in the cross sectional luminal area of the radial artery of 14.8 +/- 1.5% and 29.3 +/- 2.2%*, (*p < 0.05 vs baseline). The maximal increase (dilatory capacity) was 53.8 +/- 3.8% (mean diameter at baseline: 2.7 +/- 0.1 mm, maximal 3.4 +/- 0.1 mm, p < 0.001). The nitrate sensitivity of the radial artery was estimated by calculation of the ED50, the dose that caused half-maximal dilation of the radial artery. The ED50 of the radial artery was 0.13 +/- 0.003 microgram/kg/min. In conclusion, nitroglycerin leads to a dose dependent dilatation of peripheral conductance vessels. Low doses of 0.05 and 0.15 microgram/kg/min lead to significant arterial dilation. The maximal dilatory capacity of the radial artery is 53.8 +/- 3.5%.


How We Got to Where We Are: the Ribosome in the 21st Century.
This article is a short, informal history of the ribosome field that begins with the emergence of the field in the 1930s and ends with a description of its state in 2007, the year this essay was written. The growth in our understanding of both the role of the ribosome in protein synthesis and its structure is emphasized. Starting in 2000, the field experienced a massive upheaval as a result of the publication of the first atomic-resolution crystal structures for ribosomes. However, by 2007, the field had recovered sufficiently so that one could begin to understand how it was likely to evolve in its "poststructural" era. For that reason, this essay is about as useful as a short history of the ribosome field today as it was several years ago, when it was written.


The neurogenetics of mucolipidosis type IV.
Mucolipidosis type IV (MLIV) is an autosomal recessive disease caused by mutations in the MCOLN1 gene that codes for mucolipin, a member of the transient receptor potential (TRP) gene family. To comprehensively characterize the clinical and genetic abnormalities of MLIV. Twenty-eight patients with MLIV, aged 2 to 25 years, were studied. Ten returned for follow-up every 1 to 2 years for up to 5 years. Standard clinical, neuroimaging, neurophysiologic, and genetic techniques were used. All patients had varying degrees of corneal clouding, with progressive optic atrophy and retinal dystrophy. Twenty-three patients had severe motor and mental impairment. Motor function deteriorated in three patients and remained stable in the rest. All had a constitutive achlorhydria with elevated plasma gastrin level, and 12 had iron deficiency or anemia. Head MRI showed consistent characteristic findings of a thin corpus callosum and remained unchanged during the follow-up period. Prominent abnormalities of speech, hand usage, and swallowing were also noted. Mutations in the MCOLN1 gene were present in all patients. Correlation of the genotype with the neurologic handicap and corpus callosum dysplasia was found. MLIV is both a developmental and a degenerative disorder. The presentation as a cerebral palsy-like encephalopathy may delay diagnosis.


Biodegradation of di(2-ethylhexyl) phthalate by a new bacterial consortium.
Di(2-ethylhexyl) phthalate (DEHP) with continuous high concentration was used as the sole carbon and energy source to isolate a new bacterial consortium (K1) from agricultural soil covered with plastic film for a long time. Unclassified Comamonadaceae, Achromobacter, and Pseudomonas in K1 were identified as major genera of the consortium by high-throughput sequencing, and unclassified Commanadaceae was first reported to be related to DEHP degradation. Response surface method (RSM) showed that the optimum conditions for K1 to degrade DEHP were 31.4 °C, pH 7.3, and a concentration of 420 mg L-1. K1 maintains normal cell viability and stable DEHP degradation efficiency in the range of 10-3000 mg L-1 DEHP concentration, which is superior to existing research. The biodegradation of DEHP followed first-order kinetics when the initial concentration of DEHP was between 100 and 3,000 mg L-1. GC-MS analysis of different treatment groups showed that DEHP was degraded by the consortium group through the de-esterification pathway, and treatment effect was significantly better than that of the single bacteria treatment group. The subsequent substrate utilization experiment further confirmed that K1 could quickly mineralize DEHP. In addition, K1 has high degradation capacity for the most common phthalate acid esters in the environment.


Resident rounds. Part III: case report: temporary traumatic discoloration from handling moss-covered firewood.
Pattern recognition remains a valuable tool in the accurate diagnosis of dermatologic disease. A comprehensive patient history and physical examination denote cornerstones of medical evaluation, and in our specialty, dermoscopy can supplement data gathering to allocate cutaneous eruptions into appropriate categories. We present a case of acute onset palmar discoloration occurring in an otherwise healthy patient. Correct diagnosis transpired in the clinical setting with tailored questioning based on careful examination and adjunct dermatoscopic evaluation.


Prognosis and effectiveness of chemotherapy for medullary breast carcinoma.
We aimed to determine the prognosis and potential benefit of postoperative chemotherapy according to subtype of medullary breast carcinoma (MedBC), a very rare invasive breast cancer. A cohort of 1518 female patients with unilateral MedBC and 284,544 invasive ductal carcinoma (IDC) cases were enrolled from the Japanese Breast Cancer Registry. Prognosis of MedBC was compared to IDC among patients with estrogen receptor (ER)-negative and HER2-negative subtype (553 exact-matched patients) and ER-positive and HER2-negative subtype (163 MedBC and 489 IDC patients via Cox regression). Disease free-survival (DFS) and overall survival (OS) were compared between propensity score-matched adjuvant chemotherapy users and non-users with ER-negative and HER2-negative MedBC. Among ER-negative and HER2-negative subtype patients, DFS (hazard ratio (HR) 0.45; 95% confidence interval (95% CI), 0.30-0.68; log-rank P < 0.001) and OS (HR 0.51; 95% CI 0.32-0.83; log-rank P = 0.004) were significantly better in MedBC than IDC. Patients treated with postoperative chemotherapy showed better DFS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) and OS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) compared to those without. For the ER-positive and HER2-negative subtype, the point estimate for HR for DFS was 0.60 (95% CI 0.24-1.22) while that for OS was 0.98 (95% CI 0.46-1.84) for MedBC. In ER-negative and HER2-negative MedBC, the risk of recurrence and death was significantly lower than that of IDC, about half. Postoperative chemotherapy reduced recurrence and mortality. ER-positive and HER2-negative MedBC may have a lower risk of recurrence compared to IDC.


The expression of GLUT8, GLUT9a, and GLUT9b in the mouse testis and sperm.
The objective of this study is to confirm the precise glucose transporter (GLUT) 8 localization and determine the expression of GLUT9a and GLUT9b by Western blot and confocal and immunoelectron microscopy in the mouse testis and sperm. GLUT8, GLUT9a, and GLUT9b proteins are expressed in the most intraseminiferous tubula cells and Leydig cells. GLUT8 localizes in the midpiece and principal piece as well as in the acrosomal region of the sperm. Immunoelectron microscopic analysis shows that GLUT8 is strongly detectable at the acrosome and neck region of the sperm. In the midpiece, GLUT8 localizes at the outer dense fibers (odf) as well as at the circumference of the spiral mitochondria. In the principal piece, GLUT8 localizes at the odf. GLUT9a strictly localizes in the midpiece, but GLUT9b localizes in the acrosome, midpiece, and principal piece of the sperm. These results suggest that glucose uptake via GLUT8, GLUT9a, and GLUT9b likely affects normal spermatogenesis, steroidogenesis, and sperm function in the mouse.


Tumorigenicity and metastatic behavior in nude mice of two human squamous cell carcinoma lines that differ in production of the cytokine ETAF/IL-1.
The purpose of these studies was to determine whether the production of the cytokine epidermal cell thymocyte-activating factor (ETAF) by human squamous cell carcinoma (SCC) cells correlated with their tumorigenicity and metastatic potential in athymic nude mice. Cells of the human SCC line A431 produced rapidly growing subcutaneous tumors, few experimental lung metastases, and low levels of ETAF activity in vitro. In contrast, cells of the SCC Colo-16 line produced slower growing subcutaneous tumors, high numbers of experimental lung metastases, and a high level of ETAF activity in culture supernatants. The apparent relationship between production of ETAF and experimental metastasis formation was not consistent. Clonal populations of the SCC A431 and Colo-16 were isolated in vitro. The clones of Colo-16 varied in their ability to produce experimental metastases and in production of ETAF in vitro. However, the levels of ETAF production did not correlate with the propensity of the SCC cells to produce experimental metastases. We conclude that while the growth and metastasis of human SCC in nude mice may benefit from production of the cytokine ETAF, the ETAF production per se is not invariably linked with the capability of the SCC cells to metastasize.


Duration of plant damage by host larvae affects attraction of two parasitoid species (Microplitis croceipes and Cotesia marginiventris) to cotton: implications for interspecific competition.
Volatile organic compounds (VOCs) released by herbivore-damaged plants can guide parasitoids to their hosts. The quantity and quality of VOC blends emitted by plants may be affected by the duration of plant damage by herbivores, which could have potential ramifications on the recruitment of competing parasitoids. We used two parasitoid species, Microplitis croceipes and Cotesia marginiventris (Hymenoptera: Braconidae), to address the question of whether duration of plant damage affects parasitoid use of plant VOCs for host location. Both wasp species are larval endoparasitoids of Heliothis virescens (Lepidoptera: Noctuidae), an important pest of cotton. Attraction of the two parasitoid species to odors emitted by undamaged (UD), fresh (6 h infestation) damage (FD), and old (24 h infestation) damage (OD) cotton plants infested by H. virescens larvae was investigated using a headspace volatile collection system coupled with four-choice olfactometer bioassay. Both sexes of M. croceipes showed a preference for FD- and OD-plant odors over UD-plants. On the other hand, more C. marginiventris females were attracted to UD- and FD-plants than to OD-plants. GC/MS analyses showed qualitative and quantitative differences in the VOC profiles of UD, FD, and OD-plants, which may explain the observed preferences of the parasitoids. These results suggest a temporal partitioning in the recruitment of M. croceipes and C. marginiventris to H. virescens-damaged cotton, and may have potential implications for interspecific competition between the two parasitoid species.


Sol-gel derived xanthan gum/silica nanocomposite-a highly efficient cationic dyes adsorbent in aqueous system.
A sol-gel synthesis of nanocomposite adsorbent materials by dehydroxylation condensation of tetraethoxysilane (TEOS) in the presence of xanthan gum (XG) using base catalyst and ethanol as co-solvent is discussed. The synthesized nanocomposite material was evaluated for their ability to adsorb cationic dyes-methylene blue (MB) and bismarck brown Y (BB) from an aqueous solution. The XG/SiO2 nanocomposite shows the ordered macro- and meso-porous structures and also exhibited large surface area, excellent chemical/mechanical stability and high binding capability for MB and BB dyes. Different parameters such as pH, adsorbent dose and initial concentration were studied. The adsorption behaviour of the nanocomposite was investigated by performing both kinetics and equilibrium studies under batch conditions. The maximum adsorption capacity (Qmax) of the nanocomposite for MB and BB was found to be significantly high (432.90mgg-1 and 448.43mgg-1, respectively). The time taken for the removal of 99.4% of MB and 87.2% of BB from 100mgL-1 of dye solutions is only 35min. Thus, the proposed XG/SiO2 nanocomposite is a very promising adsorbent for the fast and efficient removal of dye from aqueous solutions.


Developmental regulation of P-45017 alpha gene expression in fetal bovine adrenal.
Among the multifactorial aspects of regulation of steroid hydroxylase gene expression, it is the developmental process which leads to imprinting of expression of particular steroid hydroxylases in specific cell types. We have begun to investigate the ontogeny of steroidogenesis in fetal bovine tissues. Expression of most steroid hydroxylases and related enzymes is detectable in adrenals of the smallest fetuses studied and continues throughout fetal life. Like the other steroid hydroxylases, P-450(17)alpha is detectable in the earliest fetal adrenals studied. However, following an increase in expression, P-450(17)alpha disappears from the fetal adrenal by 100 days gestational age and remains absent until about 230 days gestational age. The absence of P-450(17)alpha is correlated with the absence of cortisol in the fetal adrenal and the absence of ACTH in fetal plasma. Thus expression of P-450(17)alpha in bovine fetal adrenal appears to be strictly dependent on cAMP while expression of other steroid hydroxylases appears to involve both cAMP-dependent and cAMP-independent mechanisms. Furthermore, P-450(17)alpha is expressed in fetal testis at gestational times when it is absent in fetal adrenal. We have begun to examine binding of nuclear proteins from adrenals of various gestational ages to the 5'-flanking region of the bovine P-450(17)alpha gene. Preliminary evidence indicates the presence of a protein in nuclei of fetal adrenals not expressing P-450(17)alpha that is not present in fetal adrenals of other gestational ages.


Central motor reorganization in cerebral palsy patients with bilateral cerebral lesions.
Transcranial magnetic stimulation (TMS) has been used to describe cortical plasticity after unilateral cerebral lesions. The objective of this study was to find out whether cortical plasticity occurs after bilateral cerebral lesions. We investigated central motor reorganization for the arm and leg muscles in cerebral palsy (CP) patients with bilateral cerebral lesions using TMS. Seventeen patients (12 with spastic diplegia, 1 with spastic hemiplegia, and 4 with athetoid CP) and 10 normal subjects, were studied. On CT/MRI, bilateral periventricular leukomalacia was observed in all spastic patients with preterm birth. In two normal subjects, motor responses were induced in the ipsilateral tibialis anterior, but no responses were induced in any normal subject in the ipsilateral abductor pollicis brevis (APB) or biceps brachii (BB). Ipsilateral responses were more common among CP patients, especially in TMS of the less damaged hemisphere in patients with marked asymmetries in brain damage: in 3 abductor pollicis brevis, in 6 BBs, and in 15 tibialis anteriors. The cortical mapping of the sites of highest excitability demonstrated that the abductor pollicis brevis and BB sites in CP patients were nearly identical to those of the normal subjects. In patients with spastic CP born prematurely, a significant lateral shift was found for the excitability sites for the tibialis anterior. No similar lateral shift was observed in the other CP patients. These findings suggest that ipsilateral motor pathways are reinforced in both spastic and athetoid CP patients, and that a lateral shift of the motor cortical area for the leg muscle may occur in spastic CP patients with preterm birth.


Latest developments in allergic rhinitis in Allergy for clinicians and researchers.
Research efforts in allergic rhinitis have always been intense. Over the past 3 years, numerous breakthroughs in basic science and clinical research have been made, augmenting our understanding of this condition that afflicts a significant proportion of the global population. New epidemiological findings, novel insights into the molecular and cellular mechanisms of allergy, enhancement of current developmental theories, new concepts of the goals and endpoints of management, and latest therapeutic modalities that includes the harnessing of information technology and big data are some areas where important advances were made. We attempt to bring you a summary of the key research advances made in the field of allergic rhinitis from 2013 to 2015.


The effect of tumor vascular remodeling and immune microenvironment activation induced by radiotherapy: quantitative evaluation with magnetic resonance/photoacoustic dual-modality imaging.
Tumor radiotherapy combined with immunotherapy for solid tumors has been proposed, but tumor vascular structure abnormalities and immune microenvironment often affect the therapeutic effect of tumor, and multimodal imaging technology can provide more accurate and comprehensive information in tumor research. The purpose of this study was to evaluate the dynamic monitoring of tumor blood vessels and microenvironment induced by radiotherapy by magnetic resonance/photoacoustic (MR/PA) imaging, and to explore its application value in radiotherapy combined with immunotherapy. The tumor-bearing mice were randomly allocated into six groups, which received different doses of radiation therapy (2 Gy ×14 or 8 Gy ×3) and anti-programmed death ligand-1 (PD-L1) antibody for two consecutive weeks. MR/PA imaging was used to noninvasively evaluate the response of tumor to different doses of radiotherapy, combined with histopathological techniques to observe the tumor vessels and microenvironment. The inhibitory effect of high-dose radiotherapy on tumors was significantly greater than that of low-dose radiotherapy, with the MR images revealing that the signal intensity decreased significantly (P<0.05). Compared with those in the other groups, the tumor vascular density decreased significantly (P<0.01), and the vascular maturity index increased significantly in the low-dose group (P<0.05). The PA images showed that the deoxyhemoglobin and total hemoglobin levels decreased and the SO2 level increased after radiation treatment (P<0.05). In addition, the high-dose group had an increased number of tumor-infiltrating lymphocytes (CD4+ T and CD8+ T cells) (P<0.01, P<0.05) and natural killer cells (P<0.001) and increased PD-L1 expression in the tumors (P<0.05). The combination of radiotherapy and immunotherapy increased the survival rate of the mice (P<0.05), and a regimen of an 8 Gy dose of radiation combined with immunotherapy inhibited tumor growth and increased the survival rate of the mice to a greater degree than the 2 Gy radiation dose with immunotherapy combination (P=0.002). Differential fractionation radiotherapy doses exert biological effects on tumor vascular and the immune microenvironment, and MR/PA can be used to evaluate tumor vascular remodeling after radiotherapy, which has certain value for the clinical applications of radiotherapy combined with immunotherapy.


Breast phyllodes tumor: a review of literature and a single center retrospective series analysis.
Complete surgical resection is the standard treatment for localized breast phyllodes tumors. Post-surgical treatments are still a matter of debate. We carried out an overview of the literature to investigate the clinical outcome of patients with phyllodes tumor. A retrospective analysis of mono-institutional series has been included as well. We reviewed all the retrospective series reported from 1951 until April 2012. We analyzed cases treated at our institution from 1999 to 2010. Eighty-three articles (5530 patients; 1956 malignant tumors) were reviewed. Local recurrences were independent of histology. Distant recurrences were more frequent in the malignant tumors (22%). A total of 172 phyllodes tumors were included in the retrospective analysis. Prognosis of phyllodes tumors is excellent. There are no convincing data to recommend any adjuvant treatment after surgery. Molecular characterization may well provide new clues to permit identification of active treatments for the rare poor prognosis cases.


Assessment of chromosome stability in boars.
Chromosome instability adversely affects animal fertility and reproduction. Analysis of instability can be a valuable diagnostic tool. Helpful tests for assessment of instabilities include the sister chromatid exchange assay, identification of fragile sites, the bleomycin assay and the comet assay. These techniques can be used to assess and compare the chromosome stability of individual breeds of animals. The aim of the study was to assess chromosome stability in boars: Duroc, Duroc x Pietrain and Pietrain x Duroc crossbreds, Polish Large White, and the Neckar, P76 and PIC lines. The study assessed the chromosome stability of boars. The distribution of instabilities in individual breeds was varied. The average frequency of chromatid exchange was 4.8 ± 1.5, while that of fragile sites was 3.9 ± 1.4. The mean level of DNA damage (% tail DNA) was 9.4 ± 8.3, while in the bleomycin assay b/c and %AM were 0.6 ± 0.7 and 44.4 ± 4.1. A higher rate of instability was found in older individuals than in younger ones. The cytogenetic assays used to identify various forms of chromosome instability can be used to evaluate boars intended for breeding.


Disguised as a Sulfate Reducer: Growth of the Deltaproteobacterium Desulfurivibrio alkaliphilus by Sulfide Oxidation with Nitrate.
This study demonstrates that the deltaproteobacterium Desulfurivibrio alkaliphilus can grow chemolithotrophically by coupling sulfide oxidation to the dissimilatory reduction of nitrate and nitrite to ammonium. Key genes of known sulfide oxidation pathways are absent from the genome of D. alkaliphilus Instead, the genome contains all of the genes necessary for sulfate reduction, including a gene for a reductive-type dissimilatory bisulfite reductase (DSR). Despite this, growth by sulfate reduction was not observed. Transcriptomic analysis revealed a very high expression level of sulfate-reduction genes during growth by sulfide oxidation, while inhibition experiments with molybdate pointed to elemental sulfur/polysulfides as intermediates. Consequently, we propose that D. alkaliphilus initially oxidizes sulfide to elemental sulfur, which is then either disproportionated, or oxidized by a reversal of the sulfate reduction pathway. This is the first study providing evidence that a reductive-type DSR is involved in a sulfide oxidation pathway. Transcriptome sequencing further suggests that nitrate reduction to ammonium is performed by a novel type of periplasmic nitrate reductase and an unusual membrane-anchored nitrite reductase.IMPORTANCE Sulfide oxidation and sulfate reduction, the two major branches of the sulfur cycle, are usually ascribed to distinct sets of microbes with distinct diagnostic genes. Here we show a more complex picture, as D. alkaliphilus, with the genomic setup of a sulfate reducer, grows by sulfide oxidation. The high expression of genes typically involved in the sulfate reduction pathway suggests that these genes, including the reductive-type dissimilatory bisulfite reductases, are also involved in as-yet-unresolved sulfide oxidation pathways. Finally, D. alkaliphilus is closely related to cable bacteria, which grow by electrogenic sulfide oxidation. Since there are no pure cultures of cable bacteria, D. alkaliphilus may represent an exciting model organism in which to study the physiology of this process.


Development and validation of a stability-indicating assay including the isolation and characterization of degradation products of metaxalone by LC-MS.
A stability-indicating reverse-phase high-performance liquid chromatography-mass spectrometric method was developed and validated for the assay of metaxalone through forced degradation under acidic, alkaline, photo, oxidative and peroxide stress conditions. Separation of degradation products was accomplished on a reverse-phase Phenomenex C18 (250 × 4.6 mm, 5 µm) column thermostated at 25 °C using 10 mM aqueous ammonium acetate: methanol (35:65 v/v) as mobile phase in an isocratic mode of elution. The eluents were detected at 275 nm by photo diode array detector and mass detectors connected in series. Two unknown base hydrolysis products of metaxalone were identified and characterized as (a) methyl 3-(3,5-dimethylphenoxy)-2-hydroxypropylcarbamate and (b) 1-(3,5-dimethylphenoxy)-3-aminopropan-2-ol by MS, (1)H NMR and FTIR spectroscopy. The method was validated as per International Conference on Harmonization guidelines and metaxalone was selectively determined in presence of its degradation impurities, demonstrating its stability-indicating nature.


Improvement in the Photocurrent of Inverted Organic Solar Cells Using MoO(x)-Doped TAPC as a P-Type Optical Spacer.
In this work, we demonstrate enhancement in the short-circuit current of inverted organic photovoltaic cells (OPVs) using a p-type optical spacer. The p-type optical spacer, which consists of molybdenum oxide (MoO(x))-doped 1,1-bis[(di-4-tolylamino)phenyl]cyclohexane (TAPC), shows improved transmittance at visible light with high electrical conductivity. The electrical field distribution of incident light at the active layer of OPVs can be controlled by tuning the thickness of the optical spacer in the OPVs. Specifically, the incorporation of the 20-nm optical spacer layer in the OPV leads to enhanced spectral response of the device in the wavelength range of 400-600 nm, which is consistent with the combined results of improved optical absorption and better charge transport characteristics. As a result, the OPV with a 20-nm p-type optical spacer shows improvement in the short-circuit current compared with a device with 10 nm of embedded MoO(x).


Respiratory arrest after posterior fossa decompression in patients with Chiari malformations: An overview.
Chiari malformation type 1 (CM1) is a structural abnormality in the skull and cerebellum, causing cerebellar tonsils to shift downward. Decompression of the posterior fossa is a common surgical method to relieve symptoms and prevent neurological deterioration. After posterior fossa decompression (PFD), individuals with CM1 were more likely to have respiratory arrest. Here, we present, for the first time, a comprehensive overview of the potential risk factors and causes of respiratory arrest following PFD. A review of the literature highlighting the risk factors for postoperative respiratory arrest in CM1 patients was conducted in the databases of PubMed, Medline, and Google Scholar. Patients with syringomyelia and CM1 are at increased risk for respiratory arrest due to a number of factors, including impaired respiratory mechanics, central respiratory center dysfunction from edema or ischemia, intraoperative brain stem ischemia, and delayed gastric emptying from autonomic dysfunction. Occipitalization of the first cervical vertebra, basilar impression, and fusion of C2-C3 are all risk factors for respiratory arrest. Implications for CM1 patient care and prospects for further investigation of postoperative respiratory arrest's causes and risk factors were discussed.


Distinct roles for insulin and insulin-like growth factor-1 receptors in pancreatic beta-cell glucose sensing revealed by RNA silencing.
The importance of the insulin receptor (IR) and the insulin-like growth factor-1 receptor (IGF-1R) for glucose-regulated insulin secretion and gene expression in pancreatic islet beta-cells is at present unresolved. Here, we have used small interfering RNAs (siRNAs) to silence the expression of each receptor selectively in clonal MIN6 beta-cells. Reduction of IR levels by >90% completely inhibited glucose (30 mM compared with 3 mM)-induced insulin secretion, but had no effect on depolarization-stimulated secretion. IR depletion also blocked the accumulation of preproinsulin (PPI), pancreatic duodenum homoeobox-1 (PDX-1) and glucokinase (GK) mRNAs at elevated glucose concentrations, as assessed by quantitative real-time PCR analysis (TaqMan). Similarly, depletion of IGF-1R inhibited glucose-induced insulin secretion but, in contrast with the effects of IR silencing, had little impact on the regulation of gene expression by glucose. Moreover, loss of IGF-1R, but not IR, markedly inhibited glucose-stimulated increases in cytosolic and mitochondrial ATP, suggesting a role for IGF-1R in the maintenance of oxidative metabolism and in the generation of mitochondrial coupling factors. RNA silencing thus represents a useful tool for the efficient and selective inactivation of receptor tyrosine kinases in isolated beta-cells. By inhibiting glucose-stimulated insulin secretion through the inactivation of IGF-1R, this approach also demonstrates the existence of insulin-independent mechanisms whereby elevated glucose concentrations regulate PPI, PDX-1 and GK gene expression in beta-cells.


Absence of brain involvement and factors related to positive serology in a prospective series of 61 cases with pulmonary hydatid disease.
A prospective series of 65 patients with surgically confirmed lung cystic hydatid disease was evaluated in terms of their radiologic characteristics, serologic response, and presence of cysts in other organs. Cysts were mostly single and located in lower lung lobes. Liver compromise was found in 34% of the patients. Despite a systematic search, no patient showed brain cysts in this series. Twelve patients had previous hydatid disease: six in the liver and eight in the lung (two had involvement of both organs in the past). Serology using bovine cyst fluid in an immunoblot assay was 85% sensitive. Serologic response was not associated with number or cyst or compromise of other organs but was clearly associated to the presence of at least one complicated cyst. Cyst status in terms of complications should be described to allow appropriate assessment of serologic evaluations.


Designing of the fixed-dose gastroretentive bilayer tablet for sustained release of metformin and immediate release of atorvastatin.
Patients with type 2 diabetes mellitus have a high risk of cardiovascular disease mainly caused by dyslipidemia. Metformin and atorvastatin are preferentially used to treat type 2 diabetes mellitus and dyslipidemia, respectively. The aim of this study was to develop a once-a-day fixed-dose combination tablet containing metformin and atorvastatin. For this purpose, we designed gastroretentive bilayer tablets consisting of 500 mg metformin in a sustained release layer and 10 mg atorvastatin in an immediate release layer. In addition, we modified the formulation to maintain a dual release pattern for the kinetically different layers for once-daily dosing. The gastroretentive bilayer tablet was developed using polyethylene oxide as a swellable polymer and ammonium methacrylate copolymer as a granule-coating polymer with minimal use of excipients. In vitro release patterns of metformin and atorvastatin from the developed formulation were similar to those of the reference drugs, Glucophage XR for metformin and Lipitor for atorvastatin, with satisfactory dissolution similarity factor (f2) values. The pharmacokinetic study showed the sustained and immediate absorptions of metformin and atorvastatin, respectively, in beagle dogs. The 90% confidence intervals of the ratios of ln values of AUCs of test formulation F3 and respective reference formulations of metformin and atorvastatin were 0.93-1.12 and 0.89-1.17, respectively, compared with their respective reference drugs. This formulation could contribute to improving the compliance and therapeutic outcome of patients with metabolic diseases.


Dose and timing studies for the optimization of contact sensitivity in the mouse.
We investigated the effectiveness of very low doses of the contact sensitizer dinitrofluorobenzene in sensitizing BALB/cJ mice. Surprisingly, the ear swelling reactions were greater with lower dinitrofluorobenzene doses, down to one-twentieth of doses commonly used. Although it is common practice to use much lower doses at challenge than at sensitization, we found greater reactions with lower doses at sensitization than at challenge. We also studied the timing of the development and waning of reactivity to dinitrofluorobenzene, dinitrochlorobenzene and oxazolone. Reactivity peaked at day 5 for dinitrofluorobenzene and dinitrochlorobenzene, and at day 3 for oxazolone. Reactivity waned by 3 weeks with dinitrofluorobenzene and oxazolone, and by day 7 with dinitrochlorobenzene. Pretreatment with cyclophosphamide caused a delay in the development and waning of reactivity.


Heterogeneity of glycosylation of circulating active and inactive renin.
Concanavalin A chromatography was used to examine rat plasma and the incubation medium of rat renal cortical slices, the objective being to assess the heterogeneity of glycosylation of active and inactive renin. Inactive renin was measured by activation with trypsin. Concanavalin A chromatography could separate both active and inactive renin in the plasma into three forms, including the unbound form, the loosely-bound form and the tightly-bound form, thereby suggesting the presence of differently glycosylated forms of active and inactive renin in the plasma. Rat renal cortical slices secreted all these three forms of active and inactive renin, hence these forms are mainly of renal origin. These results suggest that differently glycosylated forms of active and inactive renin are released from the kidney into the blood circulation.


Antibody coated red cells with and without hemolysis in chronic ulcerative colitis.
A young female with ulcerative colitis associated with positive direct and indirect Coombs reaction and severe autoimmune hemolytic anemia is reported. Cortisone was beneficial and total colectomy was promptly followed by subsidence of the hematologic defects. Review of the literature suggests that this complication of ulcerative colitis is uncommon. It basis is unclear. It seems to be expressed through the presence of a "warm" auto-antibody. Colectomy should be strongly considered when severe hemolysis is present but not when the Coombs test is positive alone without significant hemolysis.


Studies on lead pollution: atomic absorption spectrophotometric determination of lead in hair and teeth samples.
A simple, rapid and reliable method for the determination of lead in hair and teeth samples has been described. The method incorporates digestion of the samples by nitric acid followed by atomic absorption spectrophotometric determination of lead using 283.3 nm wavelength.


mstree: A Multispecies Coalescent Approach for Estimating Ancestral Population Size and Divergence Time during Speciation with Gene Flow.
Gene flow between species may cause variations in branch length and topology of gene tree, which are beyond the expected variations from ancestral processes. These additional variations make it difficult to estimate parameters during speciation with gene flow, as the pattern of these additional variations differs with the relationship between isolation and migration. As far as we know, most methods rely on the assumption about the relationship between isolation and migration by a given model, such as the isolation-with-migration model, when estimating parameters during speciation with gene flow. In this article, we develop a multispecies coalescent approach which does not rely on any assumption about the relationship between isolation and migration when estimating parameters and is called mstree. mstree is available at https://github.com/liujunfengtop/MStree/ and uses some mathematical inequalities among several factors, which include the species divergence time, the ancestral population size, and the number of gene trees, to estimate parameters during speciation with gene flow. Using simulations, we show that the estimated values of ancestral population sizes and species divergence times are close to the true values when analyzing the simulation data sets, which are generated based on the isolation-with-initial-migration model, secondary contact model, and isolation-with-migration model. Therefore, our method is able to estimate ancestral population sizes and speciation times in the presence of different modes of gene flow and may be helpful to test different theories of speciation.


PET Imaging of Synaptic Density: Challenges and Opportunities of Synaptic Vesicle Glycoprotein 2A PET in Small Animal Imaging.
The development of novel PET imaging agents for synaptic vesicle glycoprotein 2A (SV2A) allowed for the in vivo detection of synaptic density changes, which are correlated with the progression and severity of a variety of neuropsychiatric diseases. While multiple ongoing clinical investigations using SV2A PET are expanding its applications rapidly, preclinical SV2A PET imaging in animal models is an integral component of the translation research and provides supporting and complementary information. Herein, we overview preclinical SV2A PET studies in animal models of neurodegenerative disorders and discuss the opportunities and practical challenges in small animal SV2A PET imaging. At the Yale PET Center, we have conducted SV2A PET imaging studies in animal models of multiple diseases and longitudinal SV2A PET allowed us to evaluate synaptic density dynamics in the brains of disease animal models and to assess pharmacological effects of novel interventions. In this article, we discuss key considerations when designing preclinical SV2A PET imaging studies and strategies for data analysis. Specifically, we compare the brain imaging characteristics of available SV2A tracers, i.e., [11C]UCB-J, [18F]SynVesT-1, [18F]SynVesT-2, and [18F]SDM-16, in rodent brains. We also discuss the limited spatial resolution of PET scanners for small brains and challenges of kinetic modeling. We then compare different injection routes and estimate the maximum throughput (i.e., number of animals) per radiotracer synthesis by taking into account the injectable volume for each injection method, injected mass, and radioactivity half-lives. In summary, this article provides a perspective for designing and analyzing SV2A PET imaging studies in small animals.


Outcomes in symptomatic preterm infants with postnatal cytomegalovirus infection.
Premature infants are at risk for developing symptomatic postnatal cytomegalovirus (CMV) disease, including sepsis-like syndrome. We performed a retrospective case-control study including infants born before 32 weeks of gestation and diagnosed with symptomatic postnatal CMV infection during the neonatal period. Neurodevelopmental outcome was evaluated using the Kyoto Scale of Psychological Development 2001 at 18 months of corrected age and at 3 years of age. Twenty-four infants were diagnosed with postnatal CMV infection; of them, 14 had sepsis-like symptoms and 10 had laboratory test abnormalities only. Home oxygen therapy was used significantly higher in the CMV-positive group compared with the control group at hospital discharge (52% vs 21%, P=0.032). The incidence of neurodevelopmental impairment was not significantly different between the two groups at 18 months of corrected age (29% vs 17%, P=0.48) and at 3 years of age (43% vs 29%, P=0.34). Postnatal CMV infection did not have a significant influence on neurodevelopmental outcomes of symptomatic preterm infants, although those in the CMV-positive group appeared worse. Larger studies with long-term follow-up are needed for a better understanding of continued neurodevelopmental outcomes in preterm infants with postnatal CMV infection.


Computer methods in population census data processing.
"The paper summarises the findings of an international survey of census processing methods used in the 1990 round. Extensive use is made of computers, although the technologies involved vary considerably from country to country. There is more extensive discussion of the use made of computer-assisted and automatic coding, non-keyboard data entry methods and the establishment of population databases." The geographical scope is worldwide. (SUMMARY IN FRE)


Developing new portals to safety for domestic abuse survivors in the context of the pandemic.
This study examined the emergence and implementation of community touchpoints established in the UK during the COVID-19 pandemic for victims/survivors of domestic abuse (DA). Community touchpoints are designated places, both online and in accessible settings such as pharmacies and banks, where victims/survivors can seek confidential advice and be directed to expert DA services. The research adopted a case study approach and explored a range of perspectives through expert interviews, document analysis, consultation with survivors and stakeholders and a survey of DA co-ordinators. Four national community touchpoint schemes were identified and, of these, three were implemented rapidly and were available in 2020-2021 when the UK experienced lockdowns. Partnerships between Government/voluntary organisations and commercial businesses-assisted design and implementation. Some stakeholders considered that the schemes lacked responsivity to the local context and noted challenges in providing a confidential service in rural areas. Whilst pharmacies, banks and online spaces were identified as non-stigmatised and trusted places to seek advice, community touchpoints were judged less accessible for some groups including those experiencing digital poverty and victims whose movements were heavily scrutinised. Most of the touchpoint schemes targeted adults only. There were also concerns about whether frontline staff in commercial businesses received sufficient training. Whilst robust evidence of outcomes was limited, there were indications that the schemes had achieved good reach with some early evidence of take-up. Testimonials indicated that victims/survivors were using the touchpoints in flexible ways which met their needs. Moreover, the wide reach and visibility of these initiatives delivered in non-stigmatised settings may have served to raise public awareness of DA, reducing the silence that has traditionally surrounded it. Further research into the use and impact of these initiatives is required and there may be future potential to extend community touchpoints to include children and young people experiencing DA.


Does local immersion in thermo-neutral bath influence surface EMG measurements? Results of an experimental trial.
This study investigated the effect of water immersion on surface electromyography (EMG) signals recorded from the brachioradial muscle of 11 healthy subjects, both in a dry environment and a thermo-neutral forearm bath (36 degrees C). EMG measurements were registered in a sitting position, using waterproof electrodes under 3 conditions: relaxed muscle, maximum voluntary isometric contraction (MVC, 1s, grip test) and 70% of the MVC (5 s). In relaxed muscle, mean EMG values were significantly higher under immersion compared to the dry conditions (dry: 5.4+/-3.6 microV; water: 19.5+/-14.9 microV; p=0.014). In maximum voluntary isometric contraction, there was a significant difference, though not in the same direction (dry: 145.9+/-58.9 microV; water: 73.2+/-35.0 microV; p=0.003). Under 70% MVC, there was no difference between wet and dry conditions (dry: 102.4+/-75.0 microV; water: 100.4+/-65.3 microV; p=0.951). Results suggest that dry and underwater conditions influence EMG readings; however, the results are inconsistent. These findings indicate additional influences on resting muscle activity, as well as MVC. Further measurements with other muscle groups and different types of immersion are needed to clarify conflicting observations.


Regulation of mammary differentiation by extracellular matrix involves protein-tyrosine phosphatases.
Extracellular matrix and growth factors cooperate to regulate signaling pathways and gene transcription in adherent cells. However, the mechanism of extracellular matrix signaling is poorly defined. In mammary gland, the expression of milk protein genes is controlled by cross-talk between signals derived from the basement membrane protein, laminin, and the lactogenic hormone, prolactin. Signals from basement membrane are transduced by beta1 integrins and are required for prolactin to activate DNA binding of the milk protein gene transcription factor, Stat5. Here we show that basement membrane is necessary for tyrosine phosphorylation of the prolactin receptor and thus directly affects cytokine signaling and differentiation at the level of the plasma membrane. Prolactin does not induce tyrosine phosphorylation of its receptor, Jak2, or Stat5 in nondifferentiated breast epithelia cultured on collagen I, and we show that this is due to a vanadate-sensitive activity that inhibits the prolactin pathway. We suggest that protein-tyrosine phosphatases are novel targets for regulation by extracellular matrix and in mammary cells represent an additional control to the requirement of integrins for milk protein production.


[How to choose a basic drug for psoriatic arthritis?].
On the basis of an earlier retrospective study in 270 psoriatic arthritis (PA) patients and according to the data of the literature 1. aurotherapy for the patients having mild skin changes and active joint involvement (mainly polyarticular type), 2. sulfasalazine for the patients having moderate skin changes and moderate articular activity, 3. etretinate for the patients having widespread skin involvement and mild articular activity, 4. methotrexate for the patients having both severe skin and severe articular involvement were introduced by the authors. The experiences of prospective study of 52 patients treated with disease modifying antirheumatic drugs (DMARDs) during 3-6 months are reported (21: aurothiomalate, 13: sulfasalazine, 4: methotrexate, 14: etretinate). Morning stiffness (MS), visual analog scale (VAS), number of swollen joints (No), psoriasis area and severity index (PASI) and erythrocyte sedimentation rate (ESR) were monitored. The methotrexate proved to be the most effective in every parameters, except the ESR. Regarding PASI the etretinate was the second most effective. Among the monitored parameters ESR and VAS showed significant improvement at every drugs. Withdrawal was necessary in 7 cases during aurotherapy (7/21), in 4 cases during sulfasalazine (4/13), in 4 cases during etretinate (4/14), meanwhile there was not withdrawal during methotrexate therapy. Low frequency of skin exacerbation (4/52) doesn't contraindicate the introduction of these drugs. If the choice and monitoring of psoriatic arthritis patients is correct we can detect really good results with DMARDs in PA.


Sampling a biomarker of the human immunodeficiency virus across a synthetic nanopore.
One primary goal in nanobiotechnology is designing new methodologies for molecular biomedical diagnosis at stages much earlier than currently possible and without use of expensive reagents and sophisticated equipment. In this work, we show the proof of principle for single-molecule detection of the nucleocapsid protein 7 (NCp7), a protein biomarker of the HIV-1 virus, using synthetic nanopores and the resistive-pulse technique. The biosensing mechanism relied upon specific interactions between NCp7 and aptamers of stem-loop 3 (SL3) in the packaging domain of the retroviral RNA genome. One critical step of this study was the choice of the optimal size of the nanopores for accurate, label-free determinations of the dissociation constant of the NCp7 protein-SL3 RNA aptamer complex. Therefore, we systematically investigated the NCp7 protein-SL3 RNA aptamer complex employing two categories of nanopores in a silicon nitride membrane: (i) small, whose internal diameter was smaller than 6 nm, and (ii) large, whose internal diameter was in the range of 7 to 15 nm. Here, we demonstrate that only the use of nanopores with an internal diameter that is smaller than or comparable with the largest cross-sectional size of the NCp7-SL3 aptamer complex enables accurate measurement of the dissociation constant between the two interacting partners. Notably, this determination can be accomplished without the need for prior nanopore functionalization. Moreover, using small solid-state nanopores, we demonstrate the ability to detect drug candidates that inhibit the binding interactions between NCp7 and SL3 RNA by using a test case of N-ethylmaleimide.


Spatiotemporal trends in oral cancer mortality and potential risks associated with heavy metal content in Taiwan soil.
Central and Eastern Taiwan have alarmingly high oral cancer (OC) mortality rates, however, the effect of lifestyle factors such as betel chewing cannot fully explain the observed high-risk. Elevated concentrations of heavy metals in the soil reflect somewhat the levels of exposure to the human body, which may promote cancer development in local residents. This study assesses the space-time distribution of OC mortality in Taiwan, and its association with prime factors leading to soil heavy metal content. The current research obtained OC mortality data from the Atlas of Cancer Mortality in Taiwan, 1972-2001, and derived soil heavy metals content data from a nationwide survey carried out by ROCEPA in 1985. The exploratory data analyses showed that OC mortality rates in both genders had high spatial autocorrelation (Moran's I = 0.6716 and 0.6318 for males and females). Factor analyses revealed three common factors (CFs) representing the major pattern of soil pollution in Taiwan. The results for Spatial Lag Models (SLM) showed that CF1 (Cr, Cu, Ni, and Zn) was most spatially related to male OC mortality which implicates that some metals in CF1 might play as promoters in OC etiology.


A model of the aged lung epithelium in idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is an age-related disorder that carries a universally poor prognosis and is thought to arise from repetitive micro injuries to the alveolar epithelium. To date, a major factor limiting our understanding of IPF is a deficiency of disease models, particularly in vitro models that can recapitulate the full complement of molecular attributes in the human condition. In this study, we aimed to develop a model that more closely resembles the aberrant IPF lung epithelium. By exposing mouse alveolar epithelial cells to repeated, low doses of bleomycin, instead of usual one-time exposures, we uncovered changes strikingly similar to those in the IPF lung epithelium. This included the acquisition of multiple phenotypic and functional characteristics of senescent cells and the adoption of previously described changes in mitochondrial homeostasis, including alterations in redox balance, energy production and activity of the mitochondrial unfolded protein response. We also uncovered dramatic changes in cellular metabolism and detected a profound loss of proteostasis, as characterized by the accumulation of cytoplasmic protein aggregates, dysregulated expression of chaperone proteins and decreased activity of the ubiquitin proteasome system. In summary, we describe an in vitro model that closely resembles the aberrant lung epithelium in IPF. We propose that this simple yet powerful tool could help uncover new biological mechanisms and assist in developing new pharmacological tools to treat the disease.


The structure and function of CP47 and CP43 in Photosystem II.
This Minireview presents a summary of recent investigations examining the structure and functions of the Photosystem II chlorophyll-proteins CP47 and CP43, updating our previous review which appeared in 1990 (TM Bricker, Photosynth Res 24: 1-13). Since this time, numerous studies have clarified the roles of these chlorophyll-proteins within the photosystem. Biochemical, molecular and structural studies (electron and X-ray diffraction) have demonstrated the close association of these components with the photochemical reaction center of the photosystem and with the extrinsic oxygen evolution enhancer proteins.


Professor Alfred Jost: the builder of modern sex differentiation.
Professor Alfred Jost (1916-1991) is famous for his discovery of the Mullerian inhibitor, now called anti-Mullerian hormone (AMH) or Mullerian inhibiting substance (MIS). Alfred Jost resolved the controversy surrounding the mechanism of somatic sex differentiation by proving that male characteristics must be imposed on the fetus by the testicular hormones testosterone and AMH, respectively responsible for the virilization of the Wolffian ducts, urogenital sinus and external genitalia and for the regression of Mullerian ducts. In the absence or inactivity of these hormones, the fetus becomes phenotypically female. Alfred Jost was also a pioneer through his work on testicular differentiation, in collaboration with Solange Magre. He was the first to show that testicular organization is heralded by the development of pre-Sertoli cells, which progressively surround germ cells to form seminiferous tubules. Alfred Jost did not rely only on his brilliant mind. He distrusted theories built on suboptimal experimental data and believed that intelligence was powerless without technical skill. His search for elegant, effective techniques led him to apply surgical methods to fetal endocrinology. He was also a fascinating teacher, particularly for pre-doctoral students. He died aged 75, having retired from the Collège de France, but still active as the Secrétaire Perpétuel of the French Science Academy.


Laboratory metabolic evolution improves acetate tolerance and growth on acetate of ethanologenic Escherichia coli under non-aerated conditions in glucose-mineral medium.
In this work, Escherichia coli MG1655 was engineered to produce ethanol and evolved in a laboratory process to obtain an acetate tolerant strain called MS04 (E. coli MG1655: ΔpflB, ΔadhE, ΔfrdA, ΔxylFGH, ΔldhA, PpflB::pdc ( Zm ) -adhB ( Zm ), evolved). The growth and ethanol production kinetics of strain MS04 were determined in mineral medium, mainly under non-aerated conditions, supplemented with glucose in the presence of different concentrations of sodium acetate at pH 7.0 and at different values of acid pH and a constant concentration of sodium acetate (2 g/l). Results revealed an increase in the specific growth rate, cell mass formation, and ethanol volumetric productivity at moderate concentrations of sodium acetate (2-10 g/l), in addition to a high tolerance to acetate because it was able to grow and produce a high yield of ethanol in the presence of up to 40 g/l of sodium acetate. Genomic analysis of the ΔpflB evolved strain identified that a chromosomal deletion of 27.3 kb generates the improved growth and acetate tolerance in MG1655 ΔpflB derivative strains. This deletion comprises genes related to the respiration of nitrate, repair of alkylated DNA and synthesis of the ompC gene coding for porin C, cytochromes C, thiamine, and colonic acid. Strain MS04 is advantageous for the production of ethanol from hemicellulosic hydrolysates that contain acetate.


The Ajuba LIM domain protein is a corepressor for SNAG domain mediated repression and participates in nucleocytoplasmic Shuttling.
The SNAG repression domain is comprised of a highly conserved 21-amino acid sequence, is named for its presence in the Snail/growth factor independence-1 class of zinc finger transcription factors, and is present in a variety of proto-oncogenic transcription factors and developmental regulators. The prototype SNAG domain containing oncogene, growth factor independence-1, is responsible for the development of T cell thymomas. The SNAIL proteins also encode the SNAG domain and play key roles in epithelial mesenchymal differentiation events during development and metastasis. Significantly, these oncogenic functions require a functional SNAG domain. The molecular mechanisms of SNAG domain-mediated transcriptional repression are largely unknown. Using a yeast two-hybrid strategy, we identified Ajuba, a multiple LIM domain protein that can function as a corepressor for the SNAG domain. Ajuba interacts with the SNAG domain in vitro and in vivo, colocalizes with it, and enhances SNAG-mediated transcriptional repression. Ajuba shuttles between the cytoplasm and the nucleus and may form a novel intracellular signaling system. Using an integrated reporter gene combined with chromatin immunoprecipitation, we observed rapid, SNAG-dependent assembly of a multiprotein complex that included Ajuba, SNAG, and histone modifications consistent with the repressed state. Thus, SNAG domain proteins may bind Ajuba, trapping it in the nucleus where it functions as an adapter or molecular scaffold for the assembly of macromolecular repression complexes at target promoters.


Magnetoelectricity Enhanced by Electron Redistribution in a Spin Crossover [FeCo] Complex.
Molecular-based magnetoelectric materials are among the most promising materials for next-generation magnetoelectric memory devices. However, practical application of existing molecular systems has proven difficult largely because the polarization change is far lower than the practical threshold of the ME memory devices. Herein, we successfully obtained an [FeCo] dinuclear complex that exhibits a magnetic field-induced spin crossover process, resulting in a significant polarization change of 0.45 μC cm-2. Mössbauer spectroscopy and theoretical calculations suggest that the asymmetric structural change, coupled with electron redistribution, leads to the observed polarization change. Our approach provides a new strategy toward rationally enhancing the polarization change.


Electroacupuncture therapy for arthralgia and Raynaud's phenomenon in a patient with systemic lupus erythematosus.
A 45-year-old woman with systemic lupus erythematosus presented with multiple arthralgia, coldness in fingers and toes, and Raynaud's phenomenon. Electroacupuncture (EA) therapy was performed in two courses (14 treatment sessions) 1 month apart. A needle was inserted in the proximal (or medial) side of the painful joint and another needle was inserted in the distal (or lateral) side of the same joint and a 50 Hz stimulus was applied (3 s bursts with 1 s gaps) for 15 min. A visual analogue scale was used to evaluate pain intensity. Cold provocation testing was conducted before and after EA sessions to determine the vasomotor response. Visual analogue scale scores were lower after EA sessions than before. Before starting EA, the skin temperature of the right mid fingertip was 27.9 degrees C and that of the left mid fingertip was 28.3 degrees C. In contrast, after the EA sessions, the skin temperature of the right mid fingertip was 34.8 degrees C and that of the left mid fingertip was 34.7 degrees C. In the last EA session, the patient reported that the cold in her fingers and toes had eased and Raynaud's phenomenon, in which nail colour tone changed from white to red, had disappeared. In the cold-provocation test, before EA, the temperature recovery rates of mid fingertips after cold exposure reached over 80% in 20 min. In contrast, after EA had been completed, the temperature recovery rate exceeded 80% in 10 min, thus the delay of temperature recovery was alleviated.


Isolation and structure elucidation of the major degradation products of cefaclor in the solid state.
Cefaclor is a beta-lactam antibiotic that degrades slowly under normal storage conditions to several minor products. To obtain samples large enough to permit structure elucidation, cefaclor was allowed to degrade at 40 degrees C (75% relative humidity) and at 85 degrees C. The profile of degradation products formed under these conditions is qualitatively similar to the profile of degradation products observed in samples of cefaclor aged for 14 years at room temperature, although some products found in the sample degraded at 85 degrees C are not formed at the lower temperatures. Using preparative reversed-phase high-performance liquid chromatography (rp-HPLC) and a combination of spectroscopic methods, we have isolated and characterized 17 of these degradation products. Some of these products were also isolated from studies of aqueous degradations. The major products appear to have arisen from five distinct pathways: (1) isomerization of the double bond in the dihydrothiazine ring; (2) decarboxylation; (3) ring contraction of the cephem nucleus to thiazole structures; (4) oxidative attack at carbon 4 of the dihydrothiazine ring; and (5) intramolecular attack of the primary amine of the side chain on either the beta-lactam carbonyl to form 3-phenyl-2,5-diketopiperazines or the "masked aldehyde" at carbon 6 to form 2-hydroxy-3-phenylpyrazine derivatives. The pathway involving oxidation at carbon 4 is particularly important at ambient temperatures and is unique to the solid-state degradation.


Educational Placement After Pediatric Intracerebral Hemorrhage.
This study describes educational placement of school-aged children after spontaneous intracerebral hemorrhage and examines whether educational placement is associated with severity of neurological deficits. Children with spontaneous intracerebral hemorrhage presenting from 2007 to 2013 were prospectively enrolled at three tertiary children's hospitals. The Pediatric Stroke Outcome Measure and parental interview gathered information about neurological outcome, school attendance, and educational placement. The cohort of 92 enrolled children included 42 school-aged children (6 to 17 years) with intracerebral hemorrhage. Four children died; one was excluded because of preexisting cognitive deficits. Thirty-seven children completed three-month follow-up, and 30 completed 12-month follow-up. At 12 months, 14 children (46.7%) received regular age-appropriate programming, 12 (40%) attended school with in-class services, three (10%) were in special education programs, and one child (3.3%) received home-based services because of intracerebral hemorrhage-related deficits. Of 30 children with three- and 12-month follow-up, 14 (46.7%) improved their education status, 13 (43.3%) remained at the same education level, and three (10%) began to receive in-class services. An increasing Pediatric Stroke Outcome Measure score predicted the need for educational modifications at three months (odds ratio, 3.3; 95% confidence interval, 1.4 to 7.9; P = 0.007) and at 12 months (odds ratio, 2.1; 95% confidence interval, 1.1 to 3.9; P = 0.025). Most children returned to school within a year after intracerebral hemorrhage, and many had a reduction in the intensity of educational support. However, a great need for educational services persisted at 12 months after intracerebral hemorrhage with fewer than half enrolled in regular age-appropriate classes. Worse deficits on the Pediatric Stroke Outcome Measure were associated with remedial educational placement.


Recanalization rate in patients with proximal vein thrombosis treated with the direct oral anticoagulants.
The recanalization rate in patients with deep venous thrombosis (DVT) of the legs treated with the direct oral anticoagulants (DOAC) is unknown. In an Italian cohort, we investigated the rate of residual vein thrombosis (RVT) after three and/or six months in 352 patients with proximal DVT who had been treated with the DOACs as a stand-alone therapy or lead-in parenteral anticoagulants, and compared it to that recorded in a historical cohort of 1094 patients in which vitamin K antagonists (VKAs) had been employed. In both cohorts, RVT was defined as the ultrasound persistence of thrombotic material resulting in a diameter of at least 4mm of incompressibility of the proximal veins. RVT was detected in 143 patients treated with DOACs (41.2%) after three months and in 58 patients (21.1%) after six months; the corresponding figure in patients treated with conventional anticoagulation was 52.3% and 54.5%, respectively. After adjusting for the baseline characteristics, the odds ratio of RVT in patients treated with the DOACs as compared with those treated with conventional anticoagulation was 0.63 (95% CI, 0.48-0.81) after three months, and 0.17 (95% CI; 0.11-0.26) after six months. In patients with proximal DVT treated with the DOACs, the persistence of ultrasound detectable RVT is likely to occur less frequently than in patients treated with conventional anticoagulation. These results may have implications for the prognosis of patients with DVT.


From random to rational: improving enzyme design through electric fields, second coordination sphere interactions, and conformational dynamics.
Enzymes are versatile and efficient biological catalysts that drive numerous cellular processes, motivating the development of enzyme design approaches to tailor catalysts for diverse applications. In this perspective, we investigate the unique properties of natural, evolved, and designed enzymes, recognizing their strengths and shortcomings. We highlight the challenges and limitations of current enzyme design protocols, with a particular focus on their limited consideration of long-range electrostatic and dynamic effects. We then delve deeper into the impact of the protein environment on enzyme catalysis and explore the roles of preorganized electric fields, second coordination sphere interactions, and protein dynamics for enzyme function. Furthermore, we present several case studies illustrating successful enzyme-design efforts incorporating enzyme strategies mentioned above to achieve improved catalytic properties. Finally, we envision the future of enzyme design research, spotlighting the challenges yet to be overcome and the synergy of intrinsic electric fields, second coordination sphere interactions, and conformational dynamics to push the state-of-the-art boundaries.


[Spermatic vein and artery ligation for varicocele].
To assess the influence of spermatic vein and artery ligation on testicular hemodynamics, spermatogenesis and testis volume in varicocele patients. Eighty-eight varicocele patients were randomly divided into a spermatic vein and artery ligation (n = 46) and a spermatic vein and artery preservation group (n = 42). The testicular hemodynamic parameters, testis volume and results of semen analyses were obtained before and 6 months after the surgery and compared between the two groups. There were no significant differences in peak systolic velocity (V(max)), end diastolic velocity (V(min)), mean enveloped velocity (V(mean)) and V(min) of the capsular artery (CA) either between the ligation and preservation groups (P > 0.05) or between pre- and post-operation (P > 0.05). Sperm density, vitality and motility were significantly improved after surgery (P < 0.01), with no significant differences between the two groups (P > 0.05). No significant difference was found in the testis volume between the two groups before and after the operation (P > 0.05). Spermatic vein and artery ligation in varicocelectomy does not affect the testicular hemodynamics, spermatogenesis and testis volume of varicocele patients. Both the spermatic vein and artery should be ligated when necessary.


A comprehensive review on vanilla flavor: extraction, isolation and quantification of vanillin and others constituents.
Vanilla, being the world's most popular flavoring materials, finds extensive applications in food, beverages, perfumery and pharmaceutical industry. With the high demand and limited supply of vanilla pods and the continuing increase in their cost, numerous efforts of blending and adulteration in natural vanilla extracts have been reported. Thus, to ensure the quality of vanilla extracts and vanilla-containing products, it is important to develop techniques to verify their authenticity. Quantitatively, vanillin is the major compound present in the vanilla pods and the determination of vanillin is a vital consideration in natural vanilla extracts. This paper provides a comprehensive account of different extraction processes and chromatographic techniques applied for the separation, identification and determination of chemical constituents of vanilla. The review also provides an account of different methods applied for the quantification and the authentification of chemical constituents of vanilla extract. As the various properties of vanilla are attributed to its main constituent vanillin, its physico-chemical and bioactive properties have also been outlined.


The kinetics and mechanism of shear inactivation of lipase from Candida cylindracea.
Shearing experiments were conducted in a stirred tank reactor with 0.1% lipase solutions of Candida cylindracea. Inactivation of the lipase solutions were observed at various shear rates from 50 to 150 s(-1) after continuous shearing for ca. 30-240 min under optimal pH and temperature conditions. However, there was no shear stress denaturation of the lipase when it was subjected to shear stresses of 0.72-109.2 kg/m/s(2) and shear rate of 100 s(-1). In the presence of polypropylene glycol, the rate of denaturation of the lipase decreased by 93%. When the lipase solution was filled to the brim, the rate of denaturation of the lipase decreased by 97% compared to that when reactor was half-filled. The rate of denaturation of the lipase decreased by 61% when probes in the fermentor were removed. There was no significant difference in the rate of denaturation of the lipase under ambient conditions compared with that in the absence of oxygen, or in the absence of free metal ions. Recovery of lipase activity from the first hour of shearing was observed at a shear rate of 150 s(-1). The native lipase and the lipase which had recovered its activity showed similar pH profiles, temperature profiles, and activation energies. Temperature was found to have no effect in the rate of shear-induced denaturation of the lipase in the range 20 to 30 degrees C during shearing at 100 s (-1)and optimal pH. Above 30 degrees C, the rate of denaturation of the lipase increased drastically as a function of temperature. The significance of the findings in the de sign of reactor systems for hydrolysis or esterification of oils by lipase will be discussed.


[The blocade of glutamate metabotropic 5-th tipe receptors prevents the locomotor behavior changes produced by intrastriatal picrotoxin microinjections in rats].
It was demonstrated in chronic experiments in Wistar rats that only the first of daily multiple microinjections of glutamate metabotropic 5-th type receptor antagonist MTEP into the rostral region of neostriatum impaired the avoidance conditioning in a shuttle box. Within the next two weeks, MTEP was ineffective but being injected into the neostriatum simultaneously with picrotoxin prevented the impairment of avoidance conditioning in a shuttle-box and decreased the hyperactivity (open-field locomotor hyperactivity and choreic hyperkinesis) produced by this GABA-A receptor antagonist. The results do not suggest the involvement of striatal glutamate metabotropic 5-th type receptors in avoidance conditioning control but demonstrate that glutamate metabotropic system is involved in behavioral disorders mediated by inhibition of GABA-A receptors. In principle, it might be possible to treat the human hyperkinetic basal ganglia dysfunction (Huntington's horea), athetosis and similar disorders with glutamate metabotropic receptor antagonists.


Prevalence of pregnancy induced hypertension and pregnancy outcomes among women seeking maternity services in Harare, Zimbabwe.
Pregnancy induced hypertension (PIH) is one of the most common causes of both maternal and neonatal morbidity, affecting about 5 - 8 % of pregnant women. It is associated with adverse pregnancy outcomes as well as maternal morbidity and mortality. Harare City experienced an increase in referrals due to PIH to central hospitals from 2009 to 2011. We conducted a study to determine the prevalence of PIH and pregnancy outcomes among women with PIH. An analytic cross sectional study was conducted. Interviewer administered questionnaires were used to capture demographic data, obstetric history and knowledge on PIH management. Records were reviewed for pregnancy outcomes while key informants were also interviewed on patient management. PIH prevalence was 19.4 %. Women with PIH were three times more likely to deliver a low birth weight baby (OR 3.00, p = 0.0115), 4.3 times more likely to have still birth (OR 4.34, p = 0.0517) and four times more likely to have a baby with low Apgar score at 5 minutes (OR 4.47, p = 0.0155) compared to women without PIH. There was no statistically significant difference in delivery before 37 weeks gestation between women with PIH and those without (OR 1.70, p = 0.1251). 12,5 % of the women delivered by caesarean section. Methyldopa was the drug of choice for management of PIH. Less than half of the health workers had sufficient knowledge on definition or management of PIH. Delay in seeking care and shortage of resources were the major reported challenges in the proper management of PIH. PIH prevalence was high. Women with PIH were at higher risk of adverse pregnancy outcomes than those without. Poor knowledge of management of PIH and inadequate resources are a threat to the proper management of PIH. This underscores the need for increased human resources and capacity building as well as resource mobilisation for proper management of pregnant women. Urinalysis must be routinely done for all pregnant women regardless of their blood pressure.


A Simple Quantitative Measure of Orbital Compliance.
This study evaluates the reliability of a frequently used subjective measurement of orbital compliance (0-3 scale) and describes a simple, quantitative measure with excellent intra- and interrater reliability. Two examiners performed both measurements on 100 orbits (50 consecutive patients) from the office of 1 oculoplastics surgeon. Each measurement was obtained at 2 different time points, 10 minutes apart. For the subjective measurement, the patient was asked to close their eyes, and the globe was displaced posteriorly with digital pressure until moderate resistance was felt. This was graded on a 0 to 3 scale. For the quantitative measurement (millimeter scale), the difference in axial displacement was measured using a Hertel exophthalmometer. The subjective measurement (scale, 0-3) showed excellent test-retest reliability (average, 0.901) for both examiners at both time points and good interobserver reliability (average, 0.677). The quantitative measurement (millimeter scale) showed excellent test-retest reliability (average, 0.848) and very good interobserver reliability (average, 0.756). This study shows that while both methods have both excellent test-retest reliability, the interobserver reliability is slightly higher with the quantitative measurement. This suggests that the described measurement of orbital compliance is both a reasonable alternative and possibly more accurate measurement without the steep learning curve.


Mortality from Amyotrophic Lateral Sclerosis and Parkinson's Disease Among Different Occupation Groups - United States, 1985-2011.
Amyotrophic lateral sclerosis (ALS) and Parkinson's disease, both progressive neurodegenerative diseases, affect >1 million Americans (1,2). Consistently reported risk factors for ALS include increasing age, male sex, and cigarette smoking (1); risk factors for Parkinson's disease include increasing age, male sex, and pesticide exposure, whereas cigarette smoking and caffeine consumption are inversely associated (2). Relative to cancer or respiratory diseases, the role of occupation in neurologic diseases is much less studied and less well understood (3). CDC evaluated associations between usual occupation and ALS and Parkinson's disease mortality using data from CDC's National Institute for Occupational Safety and Health (NIOSH) National Occupational Mortality Surveillance (NOMS), a population-based surveillance system that includes approximately 12.1 million deaths from 30 U.S. states.* Associations were estimated using proportionate mortality ratios (PMRs), standardizing indirectly by age, sex, race, and calendar year to the standard population of all NOMS deaths with occupation information. Occupations associated with higher socioeconomic status (SES) had elevated ALS and Parkinson's disease mortality. The shifts in the U.S. workforce toward older ages and higher SES occupations† highlight the importance of understanding this finding, which will require studies with designs that provide evidence for causality, detailed exposure assessment, and adjustment for additional potential confounders.


Candida: a review of clinical experience with Lamisil.
Pharmaceutical companies sometimes quote the MICs of antifungal agents to make favourable or unfavourable comparisons with competitor drugs. To the doctor, however, the clinical outcome is important. In this light it can be seen that topical terbinafine is certainly as effective as, if not more effective than, any other anticandidal agent available.


A dynamic coupling model for sum frequency chiral response from liquids composed of molecules with a chiral side chain and an achiral chromophore.
A theoretical formulation for optically active sum frequency generation (OA-SFG) from isotropic chiral solutions was proposed for molecules with a chiral side chain and an intrinsically achiral chromophore. Adapting an electron correlation model first proposed by Höhn and Weigang for linear optical activity, we presented a dynamic coupling model for OA-SFG near the electronic resonance of the achiral chromophore. As a demonstration, we used this model to explain the observed OA-SFG spectra of a series of amino acids near the electronic resonance of the intrinsically achiral carboxyl group. Our model shows that the nonlinear chiroptical response comes about by the through-space correlative electronic interactions between the chiral side chain and the achiral chromophore, and its magnitude is determined by the position and orientation of the bonds that make up the chiral side chain. Using the bond polarizability values in the literature and the conformations of amino acids obtained from calculation, we were able to reproduce the relative OA-SFG strength from a series of amino acids.