Expanding insight into asymmetric palladium-catalyzed allylic alkylation of N-heterocyclic molecules and cyclic ketones.
Eeny, meeny, miny ... enaminones! Lactams and imides have been shown to consistently provide enantioselectivities substantially higher than other substrate classes previously investigated in the palladium-catalyzed asymmetric decarboxylative allylic alkylation. Several new substrates have been designed to probe the contributions of electronic, steric, and stereoelectronic factors that distinguish the lactam/imide series as superior alkylation substrates (see scheme). These studies culminated in marked improvements on carbocyclic allylic alkylation substrates.


Failure of the dog culling strategy in controlling human visceral leishmaniasis in Brazil: A screening coverage issue?
In the present study, we assessed the annual screening coverage (i.e., the percentage of dogs that are screened for anti-Leishmania antibodies annually) in the municipality of Sobral, Ceará state, Brazil. Data on the number of dogs screened during 2008-2017 (except 2010) were obtained from the Centre for Zoonoses Control of Sobral. The annual screening coverage during 2012-2017 was calculated. Data on human visceral leishmaniasis (VL) cases during 2008-2017 were compiled from the National Disease Notification System. Correlation analyses were performed to assess the correlation between canine and human data. During 2008-2017, 73,964 dogs (range, 0 to 13,980 dogs/year) were serologically screened and 2,833 (3.8%) were positive. The annual screening coverage during 2012-2017 ranged from 11.1% to 45.7%. There were no significant correlations between the number of dogs culled and the number of human VL cases, canine positivity and human VL incidence, number of dogs culled and human VL incidence, or between canine positivity and number of human VL cases. An inconsistent and relatively low annual screening coverage was found in the study area, with no dog being screened in 2010 due to the lack of serological tests. Our results highlight that many dogs potentially infected with Leishmania infantum have been virtually overlooked by public health workers in the study area, perhaps with a negative, yet underestimated, impact on the control of canine and human VL. Hence, the failure of the dog culling strategy in controlling human VL in Brazil may be due to the low screening coverage and low percentage of culled dogs, rather than the absence of associations between canine and human infections.


Insulin-like growth factor binding proteins: do they play a role in polycystic ovary syndrome?
Insulin-like growth factor (IGF) binding proteins are produced by ovarian follicular cells and can oppose the effects of the IGFs and gonadotropins on these cells. Since polycystic ovarian syndrome (PCOS) is characterized by disordered follicular development, with the accumulation of antral follicles within the ovary which fail to respond appropriately to endogenous FSH, it has been hypothesized that one or more IGFBPs, which can act as FSH antagonists in vitro, could play a role in inhibiting follicular development in this syndrome. Follicular fluid IGFBP levels, however, do not differ between PCOS follicles and the androgenic, presumably atretic follicles of cycling women without PCOS. Serum IGFBP-1 levels are lower in PCOS, likely because of hyperinsulinemia, and serum free IGF-1 levels are raised. This alternation may drive the excess thecal androgen production characteristic of PCOS follicles. Alterations in IGFBPs may sustain the anovulatory steady state in PCOS but are unlikely to initiate development of the syndrome.


Increased Interleukin-17-Producing γδT Cells in the Brain Exacerbate the Pathogenesis of Sepsis-Associated Encephalopathy and Sepsis-Induced Anxiety in Mice.
Overactivated microglia play a key role in sepsis-associated encephalopathy (SAE), although the involvement of T cells is unclear. γδT cells in the brain and meninges regulate normal fear responses via interleukin (IL)-17 in healthy mice. In our sepsis model, the mice showed exacerbated anxious behavior at 10 days post-induction (dpi). At 8 dpi, IL-17 mRNA was significantly upregulated in the brains of septic mice compared with those of control mice. Simultaneously, the number of γδT cells increased in the brains of septic mice in a severity-dependent manner. Additionally, IL-17-producing γδT cells, expressing both the C-X-C motif receptor (CXCR) 6 and the C-C motif receptor (CCR) 6, increased in mice brains, dependent on the severity of sepsis. The frequency of γδT cells in the meninges fluctuated similarly to that in the brain, peaking at 8 dpi of sepsis. Behavioral tests were performed on septic mice after the continuous administration of anti-γδTCR (α-γδTCR) or anti-IL-17A (α-IL-17A) antibodies to deplete the γδT cells and IL-17A, respectively. Compared with IgG-treated septic mice, α-γδTCR- and α-IL-17A-treated septic mice showed suppressed microglial activation and improvements in anxious behavior. These results suggested that CCR6+CXCR6+ IL-17-producing γδT cells in the brain and meninges promote the exacerbation of SAE and sepsis-induced psychological disorders in mice.


The Role of Cardiac Arrest Sonographic Exam (CASE) in Predicting the Outcome of Cardiopulmonary Resuscitation; a Cross-sectional Study.
Ultrasonography (US) has been suggested as an integral part of resuscitation to identify potentially reversible causes of cardiac arrest (CA). This study aimed to evaluate the association between cardiac activity on ultrasonography during resuscitation and outcome of patients with non-shockable rhythms. We conducted a prospective, observational study on adult patients presenting with CA or experiencing CA in the emergency department (ED), and initial non-shockable rhythm. US examination of the sub-xiphoid region was performed during the 10-second interval of rhythm and pulse check and the association of US findings and patients' outcomes was evaluated. 151 patients with the mean age of 65.32 ± 11.68 years were evaluated (76.2% male). 43 patients (28.5%) demonstrated cardiac activity on the initial US. The rate of asystole in initial rhythm was 58.9% (n=89). Return of spontaneous circulation (ROSC) was achieved in 36 (23.8%) patients, twenty (13.2%) survived to hospital admission and seven (4.6%) survived to hospital discharge. When the cardiac standstill duration increased to six minutes, no patient survived hospital discharge. Potentially reversible causes were detected in 15 cases (9.9%), and four of them survived to hospital discharge. Cardiac activity on first scan was associated with ROSC (OR: 6.86, 95%CI: 2.92-16.09; p < 0.001), survival to hospital admission (OR: 17.80, 95%CI: 3.95-80.17; p < 0.001), and survival to hospital discharge (OR: 17.35, 95%CI: 2.02-148.92; p = 0.001). In non-traumatic cardiac arrest patients with non-shockable rhythms, bedside US is of great importance in predicting ROSC. The presence of pulseless electrical activity (PEA) rhythm and cardiac activity on initial US were associated with ROSC, survival to hospital admission, and hospital discharge. When the cardiac standstill duration increased to six minutes, no patient survived hospital discharge.


Anatomical and technical predictors of perioperative clinical outcomes after carotid artery stenting.
A few other studies have reported the effects of anatomical and technical factors on clinical outcomes of carotid artery stenting (CAS). This study analyzed the effect of these factors on perioperative stroke/myocardial infarction/death after CAS. This was a retrospective analysis of prospectively collected data of 409 of 456 patients who underwent CAS during the study period. A logistic regression analysis was used to determine the effects of anatomical and technical factors on perioperative stroke, death, and myocardial infarction (major adverse events [MAEs]). The MAE rate for the entire series was 4.7% (19 of 409), and the stroke rate was 2.2% (9 of 409). The stroke rate for asymptomatic patients was 0.46% (1 of 218; P = .01). The MAE rates for patients with transient ischemic attack (TIA) were 7% (11 of 158) vs 3.2% (8 of 251) for other indications (P = .077). The stroke rates for heavily calcified lesions were 6.3% (3 of 48) vs 1.2% (4 of 332) for mildly calcified/noncalcified lesions (P = .046). Differences in stroke and MAE rates regarding other anatomical features were not significant. The stroke rate for patients with percutaneous transluminal angioplasty (PTA) before embolic protection device (EPD) insertion was 9.1% (2 of 22) vs 1.8% (7 of 387) for patients without (P = .07) and 2.6% (9 of 341) for patients with poststenting PTA vs 0% (0 of 68) for patients without. The MAE rate for patients with poststenting PTA was 5.6% (19 of 341) vs 0% (0 of 68) for patients without (P = .0536). The MAE rate for patients with the ACCUNET (Abbott, Abbott Park, Ill) EPD was 1.9% (3 of 158) vs 6.7% (16 of 240) for others (P = .029). The differences between stroke and MAE rates for other technical features were not significant. A regression analysis showed that the odds ratio for stroke was 0.1 (P = .031) for asymptomatic indications, 13.7 (P = .014) for TIA indications, 6.1 (P = .0303) for PTA performed before EPD insertion, 1.7 for PTA performed before stenting, and 5.4 (P = .0315) for heavily calcified lesions. The MAE odds ratio was 0.46 (P = .0858) for asymptomatic indications, 2.1 for PTAs performed before EPD insertion, 2.2 for poststent PTAs, and 2.2 (P = .1888) for heavily calcified lesions. A multivariate analysis showed that patients with TIA had an odds ratio of stroke of 11.05 (P = .029). Patients with PTAs performed before EPD insertion had an OR of 6.15 (P = .062). Patients with heavily calcified lesions had an odds ratio of stroke of 4.25 (P = .0871). The MAE odds ratio for ACCUNET vs others was 0.27 (P = .0389). Calcific lesions and PTA before EPD insertion or after stenting were associated with higher stroke or MAE rates, or both. The ACCUNET EPD was associated with lower MAE rates. There was no correlation between other anatomical/technical variables and CAS outcome.


New woody and ambery notes from cedarwood and turpentine oil.
The development of a new product in the chemical industry is still driven by needs like technical properties, price/performance ratio, biodegradability, or product safety. However, in terms of improving more and more on ecological criteria, summarized under such catchphrases as sustainable development or green chemistry, another important aspect is to use renewable resources as starting materials. This is not significantly new in fragrance chemistry, and there are a lot of raw materials in the perfume oils that are derived from molecules of renewable resources. Two commonly used materials are: longifolene (from turpentine oil) and cedrene (from cedarwood oil). These compounds are very suitable for the synthesis of woody and ambery notes, and even though it seemed that all possibilities were exhausted, it is actually still feasible to discover new molecules with excellent olfactory properties such as Ambrocenide (50a), which is available in three steps from alpha-cedrene. Some of these molecules will be treated in this review, both with respect to synthesis as well as structural and sensory aspects.


Expression of c-erbB receptors, MMPs and VEGF in squamous cell carcinoma of the head and neck.
Head and neck squamous cell carcinomas (HNSCC) are characterized by a marked propensity for local invasion and cervical lymph node metastasis. The aim of this study was to investigate the expression of epidermal growth factor receptor (EGFR), c-erbB-2, vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in tumor samples of 91 HNSCC patients, and to study a possible correlation to various clinico-pathologic parameters. The expression of EGFR, c-erbB-2, VEGF, MMP-2, -3 and -9 was analyzed in the same paraffin embedded tissue by semi-quantitative immunohistochemical staining. High expression of EGFR, c-erbB-2, MMP-2 or -9 was associated with advanced clinical stages, nodal metastases and tumor-stages. However, high expression of VEGF or MMP-3 was not associated with any clinico-pathologic parameters except significant correlation between VEGF and the tumor site. There were significant correlations between EGFR, c-erbB-2, MMP-2 and -9 in HNSCC patients. Conversely, no correlation was found between VEGF or MMP-3 and the other markers. However, significant correlation was found between MMP-3 or -9 and VEGF. The results indicate that the expression of EGFR, c-erbB-2, VEGF or MMPs play an important role in tumor growth, invasion and metastasis in HNSCC. The authors conclude that EGFR, c-erbB-2, MMP-2 and -9 could be good independent prognostic markers, but not VEGF and MMP-3.


Physical durability of two types of long-lasting insecticidal nets (LLINs) three years after a mass LLIN distribution campaign in Mozambique, 2008-2011.
We conducted a prospective evaluation to measure the physical durability of two brands of long-lasting insecticidal nets (LLINs) distributed during a campaign in 2008 in Nampula Province, Mozambique. Households with LLINs tagged during the campaign (6,000) were geo-located (34%) and a random sample was selected for each of 3 years of follow-up. The LLINs were evaluated in the field and a laboratory for presence of holes and a proportional hole index (pHI) was calculated following the World Health Organization guidelines. We performed 567 interviews (79.0%) and found 75.3% (72.1-78.4%) of households retained at least one LLIN after 3 years; the most common cause of attrition was damage beyond repair (51.0%). Hole damage was evident after 1 year, and increased by year. Olyset had a significantly greater mean number of holes and pHI compared with PermaNet 2.0 brand (all P values ≤ 0.001). Additional information about LLIN durability is recommended to improve malaria control efforts.


Periodontitis is associated with multimorbidity in a large dental school population.
To investigate whether and which diseases co-occur with periodontitis (PD) to assess the prevalence of comorbidities and multimorbidity and to identify patterns and profiles of comorbidity and multimorbidity and the influence of demographic and lifestyle factors to identify distinct groups of multimorbid patients. A database from the Academic Centre of Dentistry Amsterdam (ACTA) with 37,801 adult individuals containing information about demographic (age, sex, socio-economic position [SEP]) and lifestyle factors (smoking, alcohol use and addictive substance use) and PD and systemic diseases was constructed. PD assessment was based on clinical information by the use of claim codes and systemic diseases data were derived from self-reported medical history. For analyses, univariable and multivariable (adjusted for age, sex, SEP, smoking, alcohol use and addictive substance use) logistic regression analyses and cluster analysis were used. Individuals with PD more often had one or multiple diseases. The adjusted odds ratio (OR) for PD patients having up to four systemic diseases ranged from 1.46 to 1.20. Co-occurrence of PD with several systemic diseases and a higher prevalence of multimorbidity was found (adjusted OR comorbidity = 1.36; 95% confidence interval (CI): 1.30-1.43; multimorbidity = 1.18; 95% CI: 1.11-1.25). Four clusters existed: cluster 1 was defined as a periodontal and systemically healthy group and cluster 4 as burdened with PD but not containing any systemic diseases. Individuals in cluster 1 were of the lowest age (44.9 [SD: 15.5]) and had the lowest prevalence of the lifestyle factors of smoking (13.6%) and alcohol use (3.9%). Clusters 2 and 3 contained both PD and had several systemic diseases but were different from each other. Cluster 2 contained 34.5% of PD individuals and had mainly respiratory tract, immune system and digestive system diseases. Cluster 3 contained 45.9% of PD individuals and had mainly cardiometabolic diseases. Cluster 2 had the highest prevalence of females (63.1%) and the highest prevalence of smokers (23.8%) and addictive substance users (8.9%). Cluster 3 included individuals of the highest age (63.5 [SD: 11.9]), and had highest prevalence of alcohol users (17.7%) and lowest prevalence of addictive substance users (3.8%). This study shows that individuals with PD are more often burdened with comorbidity and multimorbidity. Presence of distinct clusters suggests overlap in pathophysiology between certain types of PD and specific systemic diseases. Therefore, PD can be considered as part of multimorbidity, as one of the systemic diseases co-occurring in certain groups of individuals.


Prevalence rates and demographic characteristics associated with depression in pregnancy and the postpartum.
Examined the prevalence of depression in a heterogeneous sample of 360 pregnant women. Subjects were assessed with respect to both depressive symptomatology and diagnostic status during pregnancy and after delivery. At both assessments, approximately 25% of the sample reported elevated levels of depressive symptomatology. In contrast, 10% of the women met diagnostic criteria for depression during pregnancy, and 6.8% were depressed postpartum. However, only half of the cases of postpartum depression were new onset (3.4%); the remaining women receiving a diagnosis in the postpartum had also been depressed during pregnancy. Finally, depression during pregnancy was related to different sociodemographic variables than was postpartum depression, suggesting that depression at these two times may be associated with different psychological or etiological factors.


Reduction of pressor response to stress by centrally acting apelin in spontaneously hypertensive rats.
Numerous studies suggest that apelin plays a significant role in cardiovascular regulation and in the pathogenesis of hypertension. The purpose of the present study was to determine whether apelin-13 (AP-13) is involved in the regulation of cardiovascular responses to acute stress in spontaneous hypertension. The effects of intracerebroventricular (ICV) administration of AP-13 on changes in mean arterial blood pressure (MABP) and heart rate evoked by an alarming stress (air jet stress) were compared in awake normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The rats were divided into four groups: Groups 1 (WKY) and 3 (SHR) received ICV infusion of 0.9% sodium chloride (vehicle), whereas Groups 2 (WKY) and 4 (SHR) were ICV infused with AP-13. All animals were exposed to the alarming stress. During the ICV administration of the vehicle, the pressor response to stress was significantly greater in SHR than in WKY. The ICV infusion of AP-13 reduced the pressor response evoked by the application of the stressor in SHR but not in WKY. It also abolished the difference in stress-induced MABP increases between WKY and SHR. The results show that centrally acting apelin may play an essential role in the regulation of blood pressure responses to an alarming stress in SHR rats.


Decoupling wing-shape effects of wing-swept angle and aspect ratio on a forward-flying butterfly.
The effect of wing shape on a forward-flying butterfly via decoupled factors of the wing-swept angle and the aspect ratio (AR) was investigated numerically. The wing-shape effect is a major concern in the design of a microaerial vehicle (MAV). In nature, the wing of a butterfly consists of partially overlapping forewing and hindwing; when the forewing sweeps forward or backward relative to the hindwing, the wing-swept angle and the AR of the entire wing simultaneously change. The effects of the wing-swept angle and AR on aerodynamics are coupled. To decouple their effects, we established wing-shape models with varied combinations of the wing-swept angle and AR based on the experimental measurement of two butterfly species (Papilio polytes and Kallima inachus) and developed a numerical simulation for analysis. In each model, the forewing and hindwing overlapped partially, constructing a single wing. Across the models, the wing-swept angle and AR of these single wings varied sequentially. The results show that, through our models, the effects of the wing-swept angle and AR were decoupled; both have distinct flow mechanisms and aerodynamic force trends and are consistent in the two butterfly species. For a fixed AR, a backward-swept wing increases lift and drag because of the enhanced attachment of the leading-edge vortex with increased strength of the wingtip vortex and the spanwise flow. For a fixed wing-swept angle, a small AR wing increases lift and decreases drag because of the large region of low pressure downstream and the wake-capture effect. Coupling these effects, the largest lift-to-drag ratio occurs for a forward-swept wing with the smallest AR. These results indicate that, in a flapping forward flight, sweeping a forewing forward relative to a hindwing is suitable for cruising. The flow mechanisms and decoupled and coupled effects of the wing-swept angle and the AR presented in this paper provide insight into the flight of a butterfly and the design of a MAV.


Role of oxidative stress in the chemical structure-related genotoxicity of nitrofurantoin in Nrf2-deficient gpt delta mice.
Despite its antimicrobial activity, nitrofurantoin (NFT) is a renal carcinogen in rats. Oxidative stress induced by reduction of the nitro group of NFT may contribute to its genotoxicity. This is supported by our recent results indicating that the structure of the nitrofuran plays a key role in NFT-induced genotoxicity, and oxidative DNA damage is involved in renal carcinogenesis. Nuclear factor erythroid 2-related factor 2 (NRF2) regulates cellular responses to oxidative stress. To clarify the role of oxidative stress in the chemical structure-related genotoxic mechanism of NFT, we performed reporter gene mutation assays for NFT and 5-nitro-2-furaldehyde (NFA) using Nrf2-proficient and Nrf2-deficient gpt delta mice. NFT administration for 13 weeks resulted in a significant increase in 8-hydroxydeoxyguanosine (8-OHdG; a marker of oxidative stress) and gpt mutant frequency only in the kidneys of Nrf2-/- mice. The mutation spectrum, characterized by increased substitutions at guanine bases, suggested that oxidative stress is involved in NFT-induced genotoxicity. However, NFA did not increase the mutation frequency in the kidneys, despite the increased 8-OHdG in NFA-treated Nrf2-/- mice. Thus, it is unlikely that oxidative stress is involved in the genotoxic mechanism of NFA. These results imply that nitro reduction plays a key role in the genotoxicity of NFT, but the lack of a role of oxidative stress in the genotoxicity of NFA indicates a potential role of side chain interactions in oxidative stress caused by nitro reduction. These findings provide a basis for the development of safe nitrofurans.


Mitochondrial pleiomorphism in sustentacular cells of Xenopus laevis.
The mitochondrial population of sustentacular cells in the testis of the amphibian, Xenopus laevis, has been examined by electron microscopy. Three distinct types of mitochondria have been observed. The first and most common mitochondrial type is a "typical" organelle with a rod-like profile containing tubular to plate-like cristae. The second mitochondrial form is characterized externally by irregular bulbous protrusions and internally by increased numbers of tubular cristae. The third mitochondrial type, which is usually ovoid in profile, has the most unusual internal membrane configuration, consisting of pleated folds pierced by regular rows of fenestrations. Mitochondrial type one is found in all sustentacular stages, mitochondrial type two first appears in sustentacular cells surrounding early spermatids, and mitochondrial type three is observed only in sustentacular cells surrounding spermatozoa. These observations indicate that discrete subclasses of mitochondria are present in sustentacular cells of Xenopus.


Electrospray-ionization mass spectrometry for screening the specificity and stability of single-stranded-DNA templated self-assemblies.
Supramolecular complexes consisting of a single-stranded oligothymine (dTn) as the host template and an array of guest molecules equipped with a complementary diaminotriazine hydrogen-bonding unit have been studied with electrospray-ionization mass spectrometry (ESI-MS). In this hybrid construct, a supramolecular stack of guest molecules is hydrogen bonded to dTn. By changing the hydrogen-bonding motif of the DNA host template or the guest molecules, selective hydrogen bonding was proven. We were able to detect single-stranded-DNA (ssDNA)-guest complexes for strands with lengths of up to 20 bases, in which the highest complex mass detected was 15 kDa; these complexes constitute 20-component self-assembled objects. Gas-phase breakdown experiments on single- and multiple-guest-DNA assemblies gave qualitative information on the fragmentation pathways and the relative complex stabilities. We found that the guest molecules are removed from the template one by one in a highly controlled way. The stabilities of the complexes depend mainly on the molecular weight of the guest molecules, a fact suggesting that the complexes collapse in the gas phase. By mixing two different guests with the ssDNA template, a multicomponent dynamic library can be created. Our results demonstrate that ESI-MS is a powerful tool to analyze supramolecular ssDNA complexes in great detail.


Synergistic photothermal/photodynamic suppression of prostatic carcinoma by targeted biodegradable MnO2 nanosheets.
The biodegradability and clearance of metal-based nanomaterials have been questioned worldwide, which have greatly limited their clinical translation. Herein, ultrathin manganese dioxide (MnO2) nanosheets with broad near-infrared (NIR) absorption and pH-dependent degradation properties were prepared. After being modified with polyethylene glycol-cyclic arginine-glycineaspartic acid tripeptide (PEG-cRGD), the MnO2 nanosheets were then used as photothermal agent and nanocarrier to encapsulate chlorin e6 (Ce6) for targeted photothermal (PTT) and photodynamic (PDT) of cancer. As expected, the MnO2-PEG-cRGD nanosheets show high Ce6 loading capacity (351 mg/g), superb photothermal conversion performance (37.2%) and excellent colloidal stability. These nanosheets also exhibit pH-dependent and NIR-induced Ce6 release. Furthermore, the MnO2 nanosheets can be degraded by reacting with hydrogen peroxide in the acidic microenvironment, which are able to elevate the oxygen concentration in situ and thus reverses the tumor hypoxia. Thanks to these favorable properties and the cRGD-mediated tumor-targeted ability, the fabricated MnO2-PEG-cRGD/Ce6 nanocomposites can be effectively up taken by alpha-v beta-3 (αvβ3) integrin over-expressed prostatic carcinoma PC3 cells and achieve favorable therapeutic outcomes under a single 660 nm NIR laser, which is also verified by in vitro studies. The biodegradable MnO2-PEG-cRGD/Ce6 nanosheets developed in this work can be a promising nanoplatform for synergetic PTT/PDT cancer therapy.


Fermentation reactions of Actinobacillus and Pasteurella in commercial media.
The applicability, reliability and accuracy of various carbohydrate media in the determination of fermentation reactions of 16 Pasteurella and Actinobacillus isolates were investigated. Laboratory prepared and commercially prepared carbohydrate media were inoculated with known test organisms and results were compared with those obtained at the Center for Disease Control (CDC). Only two of the 15 media tested reproduced more than 90 per cent of the reactions obtained at CDC. Significant differences in performance were noted depending on source and type of dehydrated media, manufacturer, type of carbohydrate and isolate studied. Considerations for media selection are summarized.


Disubstituted pyridines: the double-coupling approach.
A one-pot procedure leading to disubstituted pyridines from the starting dibromopyridines is described. Key features include the ability to couple a range of aryl and even alkenylboronic acids at the 2,3 and/or 2,5 positions with excellent regiocontrol under a standard set of conditions. Further, isolated yields are greatly improved by the use of neutral alumina in place of silica for product purification. Finally, the intrinsic electronic bias of the pyridine ring can be overcome by using a bromoiodopyridine.


[A case of malignant paraganglioma arising from the retroperitoneum].
We report the case of 38-year-old male with a malignant and functional paraganglioma arising from the retroperitoneum. He was admitted to our hospital with a pathological fracture of the right femur, A diagnosis of paraganglioma was made after taking a biopsy specimen and discovering a hypervascular retroperitoneal tumor. The level of catecholamine in his urine was greatly increased, accompanied with hypertension, rapid pulse and sweating. He was treated with chemotherapy, radiotherapy and surgical therapy. However, he died from pulmonary metastasis.


Overdose with antiepileptic drugs: the efficacy of extracorporeal removal techniques.
Drug overdose is a growing problem among adolescents. Clinical severity depends on the drug and ingested amount, which in some cases may be life-threatening. We present a clinical case of a previously healthy teenage girl who ingested 16.4 g of carbamazepine and 14.5 g of valproic acid. She presented with profound disturbance of consciousness and toxic levels of both drugs, raised in the first hours after the ingestion. She was successfully treated with charcoal haemoperfusion followed by continuous venovenous hemodiafiltration. Overdose with the two drugs separately is common, but there are no reports of intoxication by simultaneous ingestion. High levels of carbamazepine and valproic acid can lead to severe systemic effects and management is made difficult by the absence of specific antidotes. Extracorporeal removal techniques are a good therapeutic option in these cases as they enhance the clearance by reducing the half-life of both drugs thereby preventing serious complications.


Catecholaminergic innervation of guinea pig superior olivary complex.
In mammals, olivocochlear neurons in the superior olivary complex project to the cochlea, providing input to outer hair cells and auditory afferents contacting inner hair cells. In the rat it has been demonstrated that olivocochlear neurons receive noradrenergic input, arising from the locus coeruleus and it has been demonstrated in this species using in vitro brain slices that noradrenaline exerts a direct, mostly excitatory effect on an olivocochlear subpopulation. The guinea pig is a more commonly used animal in auditory physiology than the rat and anatomical data on noradrenaline in the auditory brainstem in this species are lacking. Because it has been shown that a compact locus coeruleus is not present in the guinea pig, subtle species differences might be expected. Therefore, using immunohistochemical and tracing techniques we have investigated in the guinea pig (1) the noradrenergic and dopaminergic innervation of the superior olivary complex, (2) the anatomical relationship between noradrenergic fibres and olivocochlear neurons and (3) the origin of the noradrenergic input to this brainstem region. The results show that the guinea pig superior olivary complex receives moderately dense noradrenergic innervation and no dopaminergic innervation. In addition, noradrenergic fibres and varicosities were observed in close contact with both somata and dendrites of olivocochlear neurons, strongly suggestive of synaptic contacts. Finally the results show that a significant component of the noradrenergic innervation of the guinea pig superior olivary complex arises in the locus subcoeruleus, which is a structure likely to be the homologue of the locus coeruleus in rats and other species.


NK cells from human MHC class I (HLA-B) transgenic mice do not mediate hybrid resistance killing against parental nontransgenic cells.
We have investigated the capacity of human MHC class I HLA-B gene products, HLA-B27, -B7 (fully human), and -B7kb (human-mouse hybrid consisting of the alpha1 and alpha2 domains of HLA-B7, and the alpha3 and cytoplasmic domains of mouse H-2Kb), expressed on mouse NK cells during ontogeny to influence NK recognition of otherwise syngeneic mouse target cells. Despite a high level of surface expression of the transgene (comparable to that of endogeneous H-2DbKb molecules), the direct killing of YAC-1 targets, and the killing of P815 targets in a redirected lysis assay, the NK effectors of these transgenic mice could not mediate hybrid resistance-like killing of nontransgenic C57BL/6 target cells either in vitro or in vivo. Splenocytes from B6-B27 mice could be used to generate CTL lines against a B27-binding peptide, implying that T cells restricted by HLA-B27 developed during ontogeny. NK cells from B6-B27 could lyse B6-B27 Con A lymphoblasts pulsed with Db-binding peptide but not B27-binding peptides. Taken together, our results show that these human HLA-B transgene products cannot function as class I MHC "self" elements for mouse NK cells, even when present throughout ontogeny.


Single-cell measurement of ammonium and bicarbonate uptake within a photosymbiotic bioeroding sponge.
Some of the most aggressive coral-excavating sponges host intracellular dinoflagellates from the genus Symbiodinium, which are hypothesized to provide the sponges with autotrophic energy that powers bioerosion. Investigations of the contribution of Symbiodinium to host metabolism and particularly inorganic nutrient recycling are complicated, however, by the presence of alternative prokaryotic candidates for this role. Here, novel methods are used to study nutrient assimilation and transfer within and between the outer-layer cells of the Indopacific bioeroding sponge Cliona orientalis. Combining stable isotope labelling, transmission electron microscopy (TEM) and nanoscale secondary ion mass spectrometry (NanoSIMS), we visualize and measure metabolic activity at the individual cell level, tracking the fate of 15N-ammonium and 13C-bicarbonate within the intact holobiont. We found strong uptake of both inorganic sources (especially 13C-bicarbonate) by Symbiodinium cells. Labelled organic nutrients were translocated from Symbiodinium to the Symbiodinium-hosting sponge cells within 6 h, and occasionally to other sponge cells within 3 days. By contrast, prokaryotic symbionts were not observed to participate in inorganic nutrient assimilation in the outer layers of the sponge. Our findings strongly support the metabolic interaction between the sponge and dinoflagellates, shedding light on the ecological advantages and adaptive capacity of photosymbiotic bioeroding sponges in oligotrophic marine habitats.


[Atrial Fibrillation: Stroke Prevention in Clinical Practice Physician].
Atrial fibrillation: stroke prevention in clinical practice physician Atrial fibrillation (AF) - one of the most common arrhythmias. In patients with atrial fibrillation increases the risk of stroke 5 times, and the main method of prevention - the appointment of anticoagulant therapy. The aim of the present study were the analysis of the prevalence of risk factors for stroke in patients with AF and quality evaluation of stroke prevention in clinical practice physician.


Effects of an anti-transforming growth factor-β agent (pirfenidone) on strabismus surgery in rabbits.
To evaluate the usefulness of an anti-transforming growth factor-β (TGF-β) agent, pirfenidone (PFD) on postoperative inflammation and fibrosis following strabismus surgery in rabbits. Both eyes of 16 New Zealand white rabbits underwent reinsertion of the superior rectus muscle (SRM). After reinsertion of the SRM, PFD-loaded liposomes (0.5 mg/ml) were injected into the right eye (PFD group) and normal saline-loaded liposomes was injected into the left eye (control group), subconjunctivally (0.4 ml). To assess the postoperative inflammatory changes and fibrosis of the SRM, immunofluorescence staining with anti-CD11b antibody was performed at 3 days postoperatively, and Masson's trichrome staining was performed at 4 weeks postoperatively. To evaluate the toxicity of PFD on muscle fibers, the integrity of the muscle fibers was examined by transmission electron microscopy (TEM) at 3 days and 4 weeks postoperatively. CD11b protein expression was significantly reduced in the PFD group compared with the control group at 3 days postoperatively (p = 0.012). Masson trichrome staining, which stains collagen, was diminished in the PFD group at 4 weeks postoperatively. TEM revealed disorganized muscle fibers and vacuoles in both groups, but this was less prominent in the PFD group. Intraoperative injection of PFD may be effective as an adjunctive treatment to decrease inflammation and fibrosis resulting from strabismus surgery.


Local-in-Time Error in Variational Quantum Dynamics.
The McLachlan "minimum-distance" principle for optimizing approximate solutions of the time-dependent Schrödinger equation is revisited, with a focus on the local-in-time error accompanying the variational solutions. Simple, exact expressions are provided for this error, which are then evaluated in illustrative cases, notably the widely used mean-field approach and the adiabatic quantum molecular dynamics. Based on these findings, we demonstrate the rigorous formulation of an adaptive scheme that resizes on the fly the underlying variational manifold and, hence, optimizes the overall computational cost of a quantum dynamical simulation. Such adaptive schemes are a crucial requirement for devising and applying direct quantum dynamical methods to molecular and condensed-phase problems.


Progressive prosopagnosia: clinical and neuroimaging results.
The authors report the longitudinal case study of a patient with the right temporal variant of frontotemporal lobar degeneration. His deficit, initially limited to visuoperceptual disturbances, progressed 2 years later to a severe semantic breakdown. Neuroimaging data indicate that the underlying degenerative process, initially confined to unimodal visual associative cortices, progressed along the ventral pathways to multimodal areas in charge of integrating knowledge from various modalities (the anterior temporal lobes).


Role of midbrain ventro-lateral tegmental area (VTA) enkephalinergic mechanisms in the facilitation of hypothalamically-induced predatory attack behaviour.
Bipolar concentric electrodes were implanted in five cats in extreme lateral regions of hypothalamus. These sites were electrically stimulated using biphasic square wave pulses at a current strength ranging from 300-800 microA to evoke predatory attack on an anaesthetized but live rat. At lower current strength (300 microA) only alertness with pupillary dilatation was produced. Gradual increase in the current strength led to the recruitment of somatic and affective components and a predatory attack was exhibited at a mean current strength of 700 microA. A scoring system allowed the construction of stimulus response curves, which remained fairly constant when repeated over a period of 3-4 weeks. Bilateral microinjections of delta-alanine methoinine enkephaline (DAME) (500 ng in 0.5 microliter saline) in ventrolateral tegmental area (VTA) elevated the mean threshold current strength for affective components while somatomotor components were totally inhibited. The blocking effect of DAME persisted for 1 hour. Microinjections of naloxone (1 microgram) in similar volumes facilitated the response as indicated by a reduction in threshold current strength for somatomotor and affective components. Microinjections of naloxone (1 microgram) in similar volumes facilitated the response as indicated by a reduction in threshold current strength for somatomotor and affective components. Microinjections of naloxone (1 microgram) also reversed the blocking effect of DAME and the thresholds returned to the control level within 10 min while microinjection of normal saline as control had no effect. The excitatory effects of naloxone and inhibitory effects of DAME were statistically significant at P < 0.01 and P < 0.05 respectively with Wilcoxon's signed rank test. The present study indicates that enkephalinergic as well as opioidergic mechanisms operating at the midbrain (VTA) level are involved in the inhibition of predatory attack as elicited from lateral hypothalamus.


Early diagnosis and staging of prostate cancer.
The need for accurate methods of ascertaining the malignant potential of any given man's prostate cancer has never been greater than it is today. The presenters at the session of the 13th International Prostate Cancer Update addressing early diagnosis and staging of disease discussed combined-modality staging of disease; color Doppler imaging for detection of cancer; pelvic lymphadenectomy as a diagnostic tool; and a new, artificial intelligence-based model to predict survival. A summary of these presentations is provided here.


Variability in particulate concentrations in a horse training barn over time.
Exposure of horses to airborne particulates during stable confinement has been linked with airway inflammation in these animals. Understanding that link requires accurate measures of exposures and greater understanding of the sources of variability in these exposures. Area and breathing zone particulate concentrations were measured over time in order to determine the relative variability introduced by daily, monthly or between horse variations. Additionally, the relationship between area and breathing zone respirable particulate concentrations was examined. The study was conducted in a Thoroughbred training stable. Breathing zone and area respirable particulate concentrations were measured over a 30-month period. Mixed-model analysis of variance was used to determine effect of month and year at the time of sampling and the daily variance upon area particulate concentrations. The effects of hay feeding method and horse variance on breathing zone measures were included in the model. Real-time concentrations of particulate matter with an aerodynamic diameter of 10 microm or smaller (PM10) were measured to determine the effect of barn door position. Significance was set at P < 0.05. Average area particulate concentration varied with month and year of sampling but daily variation was not significant. Maximum area respirable particulate concentrations were significantly affected by daily variation. Opening barn doors resulted in lower PM10 levels. Horses fed from hay nets were exposed to significantly higher concentrations of respirable particulates in their breathing zone than when fed hay on the ground. Horse-to-horse variability was significant. Breathing zone concentrations were significantly greater than area concentrations and the 2 measurements were not correlated. While area respirable particulate concentrations reflected seasonal changes, these measures are poor predictors of individual horse exposure. Instead, methods of feeding and individual horse behaviour are important determinants of exposure. Studies investigating the effect of natural exposures on lung health in horses should consider the effects of individual behaviour and management practices on breathing zone exposure.


Case series of tracheal extubation in prone position after endoscopic retrograde cholangiopancreatography general anesthesia.
The study aims to present a 15-patient case series of tracheal extubation in the prone position after endoscopic retrograde cholangiopancreatography (ERCP) general anesthesia. Fifteen inpatients who underwent elective ERCP in our hospital were prospectively enrolled, and a series of case studies were conducted with the prone extubation technique after general anesthesia. All patients underwent routine operation of tracheal intubation under general anesthesia. After the surgery, when the train-of-four ratio (TOFr) ≥0.9, bispectral index (BIS) ≥80, tidal volume ≥6 ml/kg and the required actions could be performed, the endotracheal catheter was removed after sufficient negative pressure suction of oral secretions. After the endotracheal catheter was removed, the patient autonomously turned to the transport bed with the assistance of medical staff and was then admitted to the post-anesthesia care unit (PACU) for further observation. When the patient awoke, he had regained orientation, and presented stable vital signs, no nausea and vomiting, and no other discomfort symptoms, he/she was able to leave PACU and returned to the ward with a Steward score of ≥5. All 15 patients who underwent ERCP elective surgery were successfully extubated in the prone position after surgery. Transient hypoxemia with SpO2 below 90% occurred in 2 of the 15 patients and returned to normal with oxygen mask administration. 7 patients had coughs and were without special treatment. Another 1 patient showed transient abnormal hemodynamic fluctuations after extubation, mean airway pressure (MAP) was higher than 20% of the baseline value, and hemodynamics was stable after drug treatment. The prone extubation technique is feasible for ERCP general anesthesia patients. However, a larger sample size is needed to validate its safety and to verify whether there exist advantages of the extubation technique in a prone position over a supine position.


Localized thin film damage sourced and monitored via pump-probe modulated thermoreflectance.
Damage in the form of dewetting and delamination of thin films is a major concern in applications requiring micro- or nano-fabrication. In non-contact nanoscale characterization, optical interrogation must be kept to energies below damage thresholds in order to conduct measurements such as pump-probe spectroscopy. In this study, we show that the thermoreflectance of thin films can indicate the degree of film damage induced by a modulated optical heating source. By adjusting the absorbed power of the pump heating event, we identify the characteristics of the change in the thermoreflectance signal when leading up to and exceeding the damage threshold of gold films of varying thicknesses on glass substrates.


Wearable Pulse Oximetry Measurements on the Torso, Arms, and Legs: A Proof of Concept.
For decades pulse oximeters designed for use on the head, hands, or feet have provided invaluable estimates of oxygen saturation to medical personal attending to combat casualties. However, traditional placement sites are not ideal for the relatively new paradigm of continuous battlefield telemonitoring. To assess the feasibility of oximetry on nontraditional body sites, 42 healthy volunteers were enrolled, consented, and underwent an industry standard induced-hypoxia study. During the study volunteers used prototype wearable oximeters, designed for the torso, arms, and legs. Subsets (size n) of the volunteers had the wearables placed at the following body sites, and achieved accuracies (ARMS, root-mean-square difference) of the following: calf 1.7% (n = 26); bicep 3.1% (n = 12); forearm 3.4% (n = 11); pectoral 2.9% (n = 42); sternum 2.9% (n = 13). In keeping with regulatory guidance calibrations with an ARMS of less than 3.5% are acceptable for potential future development. Additionally, a new method was developed to enable accurate reporting of respiration rate from the pectoral oximeter, ARMS of 1.1 breaths per minute (n = 10). This study demonstrates the feasibility of monitoring oxygen saturation and respiration rate from nontraditional sites via a wearable pulse oximeter.


Sexual Dimorphism of Metabolomic Profile in Arterial Hypertension.
Metabolomic studies have demonstrated the existence of biological signatures in blood of patients with arterial hypertension, but no study has hitherto reported the sexual dimorphism of these signatures. We compared the plasma metabolomic profiles of 28 individuals (13 women and 15 men) with essential arterial hypertension with those of a healthy control group (18 women and 18 men), using targeted metabolomics. Among the 188 metabolites explored, 152 were accurately measured. Supervised OPLS-DA (orthogonal partial least squares-discriminant analysis) showed good predictive performance for hypertension in both sexes (Q2cum = 0.59 in women and 0.60 in men) with low risk of overfitting (p-value-CV ANOVA = 0.004 in women and men). Seventy-five and 65 discriminant metabolites with a VIP (variable importance for the projection) greater than 1 were evidenced in women and men, respectively. Both sexes showed a considerable increase in phosphatidylcholines, a decrease in C16:0 with an increase in C28:1 lysophosphatidylcholines, an increase in sphingomyelins, as well as an increase of symmetric dimethylarginine (SDMA), acetyl-ornithine and hydroxyproline. Twenty-nine metabolites, involved in phospholipidic and cardiac remodeling, arginine/nitric oxide pathway and antihypertensive and insulin resistance mechanisms, discriminated the metabolic sexual dimorphism of hypertension. Our results highlight the importance of sexual dimorphism in arterial hypertension.


Gas-phase sorption-desorption of propargyl bromide and 1,3-dichloropropene on plastic materials.
The goal of this research was to provide information for choosing appropriate materials for studying gas-phase concentrations of propargyl bromide (3BP) and 1,3-dichloropropene (1,3-D) in laboratory experiments. Several materials were tested and found to sorb both gas-phase chemicals in the following order: stainless steel (SS) < Teflon polytetrafluoroethylene (PTFE-FEP) approximately flexible polyvinyl chloride (PVC) approximately acrylic < low-density polyethylene (PE) < vinyl approximately silicone < polyurethane foam (PUF). Sorption of SS was insignificant and PUF sorbed all the fumigant that was applied. For the other materials, linear sorption coefficients (Kd) for 3BP ranged from 3.0 cm3 g(-1) for PVC to 215 cm3 g(-1) for silicone. Freundlich sorption coefficients for 1,3-D ranged from 11.5 to 371 cm3 g(-1). First-order desorption rate constants in an open system ranged from 0.05 to 1.38 h(-1) for 3BP and from 0.07 to 1.73 h(-1) for 1,3-D. In a closed system, less than 2% of sorbed fumigant desorbed from vinyl while up to 99% desorbed from PVC within 24 h when equilibrated at the highest headspace concentration. Sorption of both fumigants was linearly related to the square root of time except for vinyl and silicone. This may indicate non-fickian diffusion of fumigant into the polymer matrix. Vinyl, silicone, PE, and PUF should be avoided for quantitative study of organic gases, except possibly as a trapping medium. Use of PTFE, PVC, and acrylic may require correction for sorption-desorption and diffusion.


The Radiolabeled HER3 Targeting Molecules for Tumor Imaging.
The human epidermal growth factor receptor (HER) family plays pivotal roles in physiologic and pathologic conditions (such as tumor growth, proliferation, and progression in multiple epithelial malignancies). All the family members are considered tyrosine kinase, while HER3 as a member of this family shows no intrinsic tyrosine kinase. HER3 is called 'pseudokinase' because it undergoes heterodimerization and forms dimers such as HER2-HER3 and HER1 (EGFR)-HER3. The exact role of HER3 in cancer is still unclear; however, the overexpression of this receptor is involved in the poor prognosis of malignancies. To that end, different studies investigated the development of radiotracers for imaging of HER3. The main focus of this review is to gather all the studies on developing new radiotracers for imaging of HER3.


A new technique for intraoperative blood recovery in the cancer patient.
Homologous blood transfusion in the cancer patient is dangerous because of an apparent immunodepressive action. Even a program of pre-deposit and isovolemic hemodilution, for reasons of immediacy and patient conditions, is often not feasible. Likewise, the intraoperative recovery of blood, although used by some, does not prevent the possible reinfusion of suspended neoplastic cells. A system that eliminates tumor cells could enable the recovery of blood in cancer patients in non-septic operative sites. A system that seems to correspond to these requisites has been set up by inserting two filters for the elimination of leucocytes from erythrocyte concentrates into a cell separator that is normally used in clinical practice. Laboratory studies, using immunohistochemical identification of tumor cells cultivated in vitro, have demonstrated the absence of contaminating cells in blood available for reinfusion.


Nonepithelial skin tumors with multinucleated giant cells.
Recognition of the different types of multinucleated giant cells in neoplastic and pseudotumoral lesions of the skin may be helpful in the differential diagnosis of these tumors. In this review, we will analyze the different types of multinucleated giant cells that can be found in nonepithelial cutaneous tumors and, more importantly, the clinicopathological context in which they are found. Touton giant cells are typically present in juvenile xanthogranuloma, necrobiotic xanthogranuloma, and some subtypes of xanthomas. Giant cells with a ground glass appearance are typically present in the solitary reticulohistiocytoma and multicentric reticulohistiocytosis. Osteoclast-like cells are found in giant cell tumors (GCT) of soft parts, plexiform fibrohistiocytic tumor, and atypical fibroxanthoma. Floret-like cells are present in giant cell fibroblastoma, pleomorphic lipoma, multinucleate cell angiohistiocytoma, and giant cell collagenoma.


Evaluation of the effect of platelet-rich plasma on recovery after ablative fractional photothermolysis.
Despite the advantages and reduced recovery time of ablative fractional photothermolysis, patients still seek adjuvant treatments to reduce healing time and facilitate their return to normal social and work activity. Platelet-rich plasma (PRP) has been used for many applications in various surgical fields for its ability to improve wound healing, hemostasis, and graft survival. To determine whether PRP will be an effective adjunctive treatment to fractional carbon dioxide resurfacing and reduce healing time and duration of adverse effects. Prospective blinded study of male and female patients 18 years or older and with Fitzpatrick skin types I to IV performed at Miami Institute for Age Management and Intervention. Using a fractional carbon dioxide laser (60 mJ at 150 Hz), a 1-cm2 area was treated on each forearm of every patient. Immediately after the laser treatment, patients were randomized to receive PRP in the right or left forearm and saline in the other forearm. Pictures of each forearm were taken immediately after injection of PRP and then on a daily basis until reepithelialization (eschar formation) occurred. Posttreatment erythema, edema, and reepithelialization. Significant improvement in posttreatment erythema was observed in PRP-treated arms across 94 comparisons in 15 patients. Improvement was defined as the erythema rating of the untreated arm minus the erythema rating of the PRP-treated arm. The mean (standard error of the mean) improvement in grade was 0.26 (0.092; t statistic, 2.83; P = .003). A mean (standard error of the mean) improvement in edema grade of 0.13 (0.059) was also significant across 94 comparisons (t statistic, 2.20; P = .02). Our preliminary results suggest that PRP can objectively reduce erythema and edema following carbon dioxide fractional laser treatment. Most importantly, patients themselves have noticed a reduction in the common posttreatment effects: erythema, edema, pruritus, and discomfort. We anticipate that PRP can be an efficacious adjunctive treatment to carbon dioxide laser resurfacing and can aid patients in hastening their return to their normal routine. 1.


Absolute venomics: Absolute quantification of intact venom proteins through elemental mass spectrometry.
We report the application of a hybrid element and molecular MS configuration for the parallel absolute quantification of μHPLC-separated intact sulfur-containing venom proteins, via ICP triple quadrupole MS and 32S/34S isotope dilution analysis, and identification by ESI-QToF-MS of the toxins of the medically important African black-necked spitting cobra, Naja nigricollis (Tanzania); New Guinea small-eyed snake, Micropechis ikaheka; and Papuan black snake, Pseudechis papuanus. The main advantage of this approach is that only one generic sulfur-containing standard is required to quantify each and all intact Cys- and/or Met-containing toxins of the venom proteome. The results of absolute quantification are in reasonably good agreement with previously reported relative quantification of the most abundant protein families. However, both datasets depart in the quantification of the minor ones, showing a tendency for this set of proteins to be underestimated in standard peptide-centric venomics approaches. The molecular identity, specific toxic activity, and concentration in the venom, are the pillars on which the toxicovenomics-aimed discovery of the most medically-relevant venom toxins, e.g. those that need to be neutralized by an effective therapeutic antivenom, should be based. The pioneering venom proteome-wide absolute quantification shown in this paper represents thus a significant advance towards this goal. The potential of ICP triple quadrupole MS in proteomics in general, and venomics in particular, is critically discussed. Animal venoms provide excellent model systems for investigating interactions between predators and prey, and the molecular mechanisms that contribute to adaptive protein evolution. On the other hand, numerous cases of snake bites occur yearly by encounters of humans and snakes in their shared natural environment. Snakebite envenoming is a serious global public health issue that affects the most impoverished and geopolitically disadvantaged rural communities in many tropical and subtropical countries. Unveiling the temporal and spatial patterns of venom variability is of fundamental importance to understand the molecular basis of envenoming, a prerequisite for developing therapeutic strategies against snakebite envenoming. Research on venoms has been continuously enhanced by advances in technology. The combined application of next-generation transcriptomic and venomic workflows has demonstrated unparalleled capabilities for venom characterization in unprecedented detail. However, mass spectrometry is not inherently quantitative, and this analytical limitation has sparked the development of methods to determine absolute abundance of proteins in biological samples. Here we show the potential of a hybrid element and molecular MS configuration for the parallel ESI-QToF-MS and ICP-QQQ detection and absolute quantification of intact sulfur-containing venom proteins via 32S/34S isotope dilution analysis. This configuration has been applied to quantify the toxins of the medically important African snake Naja nigricollis (Tanzania), and the Papuan species Micropechis ikaheka and Pseudechis papuanus.


A "best fit" approach for synergistic surface parameters to guide the design of candidate implant surfaces.
Human bone resorption surfaces can provide a template for endosseous implant surface design. We characterized the topography of such sites using four synergistic parameters (fractal dimension, lacunarity, porosity, and surface roughness) and compared the generated values with those obtained from two groups of candidate titanium implant surfaces. For the first group (n = 5/group): grit-blasted acid etched (BAE), BAE with either discrete calcium phosphate crystal deposition or nanotube formation, machined titanium with nanotubes, or a nanofiber surface; each measured synergistic parameter was statistically compared with that of the resorbed bone surface and scored for inclusion in a "best fit" analysis. The analysis informed changes that could be made to a candidate implant surface to render it a closer "best fit" to that of the resorbed bone surface. In a second group of either titanium or titanium alloy implants their micro-topography, created by dual acid etching, was the same for each material substrate; but their nanotopographic complexity was changed by varying the degree of calcium phosphate crystalline deposits. These implants were also used in vivo where bone anchorage was tested using a tensile disruption test; and the "best fit" of synergistic parameters coincided with the best biological outcome for both titanium and titanium alloy implants. In conclusion, the four chosen synergistic parameters can be used to guide the sub-micron surface design of candidate implants, and our "best fit" approach is capable of identifying the surfaces with the best biological outcomes. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2165-2177, 2019.


Novel Siglec-15-Sia axis inhibitor leads to colorectal cancer cell death by targeting miR-6715b-3p and oncogenes.
Siglecs are well known immunotherapeutic targets in cancer. Current checkpoint inhibitors have exhibited limited efficacy, prompting a need for novel therapeutics for targets such as Siglec-15. Presently, small molecule inhibitors targeting Siglec-15 are not explored alongside characterised regulatory mechanisms involving microRNAs in CRC progression. Therefore, a small molecule inhibitor to target Siglec-15 was elucidated in vitro and microRNA mediated inhibitor effects were investigated. Our research findings demonstrated that the SHG-8 molecule exerted significant cytotoxicity on cell viability, migration, and colony formation, with an IC50 value of approximately 20µM. SHG-8 exposure induced late apoptosis in vitro in SW480 CRC cells. Notably, miR-6715b-3p was the most upregulated miRNA in high-throughput sequencing, which was also validated via RT-qPCR. MiR-6715b-3p may regulate PTTG1IP, a potential oncogene which was validated via RT-qPCR and in silico analysis. Additionally, molecular docking studies revealed SHG-8 interactions with the Siglec-15 binding pocket with the binding affinity of -5.4 kcal/mol, highlighting its role as a small molecule inhibitor. Importantly, Siglec-15 and PD-L1 are expressed on mutually exclusive cancer cell populations, suggesting the potential for combination therapies with PD-L1 antagonists.


BRL3 and AtRGS1 cooperate to fine tune growth inhibition and ROS activation.
Plasma membrane-localized leucine-rich repeat receptor-like kinases directly activates G protein complex via interaction with seven transmembrane domain Regulator of G-protein Signaling 1 (AtRGS1) protein. Brassinosteroid insensitive 1 (BRI1) LIKE3 (BRL3) phosphorylates AtRGS1 in vitro. FRET analysis showed that BRL3 and AtRGS1 interaction dynamics change in response to glucose and flg22. Both BRL3 and AtRGS1 function in glucose sensing and brl3 and rgs1-2 single mutants are hyposensitive to high glucose as well as the brl3/rgs1 double mutant. BRL3 and AtRGS1 function in the same pathway linked to high glucose sensing. Hypocotyl elongation, another sugar-mediated pathway, is also implicated to be partially mediated by BRL3 and AtRGS1 because rgs1-2, brl3-2 and brl3-2/ rgs1-2 mutants share the long hypocotyl phenotype. BRL3 and AtRGS1 modulate the flg22-induced ROS burst and block one or more components positively regulating ROS production because the brl3/rgs1 double mutant has ~60% more ROS production than wild type while rgs1-2 has a partial ROS burst impairment and brl3 has slightly more ROS production. Here, we proposed a simple model where both BRL3 and AtRGS1 are part of a fine-tuning mechanism sensing glucose and flg22 to prevent excess ROS burst and control growth inhibition.


Temperature-Dependent n-p-n Switching and Highly Selective Room-Temperature n-SnSe2/p-SnO/n-SnSe Heterojunction-Based NO2 Gas Sensor.
Many toxic gases are mixed into the atmosphere because of increased air pollution. An efficient gas sensor is required to detect these poisonous gases with its ultrasensitive ability. We employed the thermal evaporation method to deposit an n-SnSe2/p-SnO/n-SnSe heterojunction and observed a temperature-dependent n-p-n switching NO2 gas sensor with high selectivity working at room temperature (RT). The structural and morphological properties of the material were studied using the characterization techniques such as XRD, SEM, Raman spectroscopy, XPS, and HRTEM, respectively. At RT, the device response was 256% for 5 ppm NO2. The response/recovery times were 34 s/272 s, respectively. The calculated limit of detection (LOD) was ∼115 ppb with a 38% response. The device response was better with NO2 gas than with SO2, NO, H2S, CO, H2, and NH3. The mechanism of temperature-dependent n-p-n switching, fast response, recovery, and selective detection of NO2 at RT has been discussed on the basis of physisorption and charge transfer. Thus, this work will add a new dimension to 2D materials as selective gas detectors at room temperature.


Recent Advances in Uterine Fibroid Etiology.
Uterine fibroids, also known as uterine leiomyoma (UL), are monoclonal tumors of the smooth muscle tissue layer (myometrium) of the uterus. Although ULs are considered benign, uterine fibroids are the source of major quality-of-life issues for approximately 25% of all women, who suffer from clinically significant symptoms of UL. Despite the prevalence of UL, there is no treatment option for UL which is long term, cost-effective, and leaves fertility intact. The lack of understanding about the etiology of UL contributes to the scarcity of medical therapies available. Studies have identified an important role for sex steroid hormones in the pathogenesis of UL, and have driven the use of hormonal treatment for fibroids, with mixed results. Dysregulation of cell signaling pathways, miRNA expression, and cytogenetic abnormalities have also been implicated in UL etiology. Recent discoveries on the etiology of UL and the development of relevant genetically modified rodent models of UL have started to revitalize UL research. This review outlines the major characteristics of fibroids; major contributors to UL etiology, including steroid hormones; and available preclinical animal models for UL.


[Prevalence of cardiovascular manifestations in Marfan syndrome].
Marfan syndrome is an inherited connective tissue disorder with an autosomic dominant transmission. The prevalence is 1:5000-10 000 and the clinical major criteria involve the skeletal and ocular apparatus and the cardiovascular and central nervous system. The main cause of morbidity is represented by the thoracic aortic dissection/aneurysm that is responsible for 80% of the deaths. We performed a clinical study on 227 patients enrolled at our Clinical and Research Marfan and Related Disorders Center. The aim of this study was to describe the prevalence of cardiovascular manifestation in this cohort of patients. Aortic dilation was present in 172 patients (75.8%), mitral valve prolapse in 179 (78.9%). Aortic insufficiency was present in 83 patients (36.6%), mitral insufficiency in 165 (72.7%). When analyzed separately, in < 10-year and > 40-year patients aortic dilation was more prevalent than mitral valve prolapse. Three patients presented with interatrial septal defect, 4 aortic bicuspid valve; 23 had a history of ventricular and supraventricular arrhythmias, and in 2 patients an implantable cardioverter device had been implanted. Fifty-seven patients were treated with beta-blockers and 28 had been operated for aortic aneurysmal dilation. In Marfan syndrome mitral valve prolapse and aortic dilation are the main cardiovascular manifestations, interatrial septal defect and aortic bicuspid valve had the same prevalence than in subjects without Marfan syndrome. These data refer to our first patient evaluation; further studies are needed to evaluate the progression and the natural history of cardiovascular manifestations in Marfan syndrome.


Loculated pleural empyema: identification of complement breakdown products in contiguous sterile pleural fluid.
In view of the recent demonstration of complement consumption in human empyema, we searched for evidence of complement activation in 4 patients presenting initially with sterile postpneumonic effusions, but who were later shown to have contiguous loculated pleural empyemas. These results were compared with those obtained on 13 patients with postpneumonic uncomplicated effusions, and on 13 patients with primary empyema. C3d and Ba, respectively, breakdown products of complement components C3 and Factor B were both significantly elevated in the postpneumonic effusions of the 4 patients with loculated empyemas, when compared with those obtained in postpneumonic uncomplicated effusions (p less than 0.005). Total hemolytic complement activity (CH50) was similar in these 2 groups of pleural effusions. Plasma levels of C3d and Ba were undetectable, and CH50 values were within the same range in all groups of patients. These results suggest that the low molecular weight breakdown products of C3 and Factor B had diffused from the adjacent empyema, where active complement breakdown was occurring, into the sterile postpneumonic effusion. This study provides information about complement catabolism in extravascular sites during infection. The potential usefulness of this approach for the detection of loculated purulent collections is discussed.


Follicle-stimulating hormone activates a cAMP-dependent chloride conductance in TM4 Sertoli cells.
The effect of follicle-stimulating hormone (FSH) on the electrical properties of TM4-Sertoli cells was investigated. Addition of 5 IU/ml FSH caused a dose-dependent and reversible depolarization of the resting membrane potential by +15.3 +/- 1.0 mV accompanied by a decrease of the input resistance. The depolarization was completely abolished in chloride-free solutions. The reversal potential of the effect was close to the calculated reversal potential for chloride. We conclude that FSH activates a chloride conductance in cultured TM4 Sertoli cells.


Biochemical Characteristics and a Genome-Scale Metabolic Model of an Indian Euryhaline Cyanobacterium with High Polyglucan Content.
Marine cyanobacteria are promising microbes to capture and convert atmospheric CO2 and light into biomass and valuable industrial bio-products. Yet, reports on metabolic characteristics of non-model cyanobacteria are scarce. In this report, we show that an Indian euryhaline Synechococcus sp. BDU 130192 has biomass accumulation comparable to a model marine cyanobacterium and contains approximately double the amount of total carbohydrates, but significantly lower protein levels compared to Synechococcus sp. PCC 7002 cells. Based on its annotated chromosomal genome sequence, we present a genome scale metabolic model (GSMM) of this cyanobacterium, which we have named as iSyn706. The model includes 706 genes, 908 reactions, and 900 metabolites. The difference in the flux balance analysis (FBA) predicted flux distributions between Synechococcus sp. PCC 7002 and Synechococcus sp. BDU130192 strains mimicked the differences in their biomass compositions. Model-predicted oxygen evolution rate for Synechococcus sp. BDU130192 was found to be close to the experimentally-measured value. The model was analyzed to determine the potential of the strain for the production of various industrially-useful products without affecting growth significantly. This model will be helpful to researchers interested in understanding the metabolism as well as to design metabolic engineering strategies for the production of industrially-relevant compounds.


Diagnosis of Diabetes Mellitus in Older Adults.
In the United States, 4 out of 10 adults with diabetes are ≥65 years of age. The older adult with diabetes is very likely to be asymptomatic and also at higher risk of vascular disease. New concerns include new diagnosis of diabetes for older adults admitted to hospital and older adults in long-term care facilities. The pathophysiology for increased incidence of diabetes in older adults is multifactorial, but dominant features are increased likelihood of metabolic syndrome, dysfunctional insulin secretion, and peripheral insulin resistance. Society in general benefits from more cost-effective care of older adults with diabetes.


[Recurrent sarcoidosis in skin scars disclosing repeated thoracic sarcoidosis].
Recurrence of thoracic sarcoidosis after spontaneous regression is extremely rare. Its existence is proven by two new cases associating sarcoidosis with L ofgren 's syndrome and sarcoid in skin scars, the latter facilitating the recognition of the presence of thoracic disease. Surveillance of the behaviour of scars forms part of routine examinations in the sarcoid patient. Even when there has been total spontaneous regression, subsequent clinical and radiological follow-up every two years must be continued.


[Characteristics of atherosclerotic plaque in diabetics].
Diabetes is associated with a high risk for early atherosclerosis. 3/4 of all Type-2 diabetic patients exhibit coronary artery disease. Microcirculatory disturbances precede morphologic changes. Especially fluctuations in blood glucose which occur i.e. in the postprandial state in badly controlled diabetic subjects, lead to an activation of protein kinase C beta and to stimulation of extracellular matrix proteins and cytokines. NO-dependent vasodilation is reduced. Postprandial blood glucose peaks are correlated with the intima-media thickness of the carotid artery and appear to be more important than fasting glucose values in multivariate analyses. After coronary interventions there is an enhanced plasminogen activator inhibitor-1 synthesis in diabetic patients compared to controls. This enhanced synthesis contributes to an exaggerated intravascular thrombogenicity. Already within a few days statin therapy leads to an increase in vasodilatory capacity irrespective of plasma lipid concentrations. Atherosclerosis and development of plaques are functionally and morphologically different between diabetic patients and controls. Blood glucose fluctuations, mainly occurring in the postprandial state enhance atherosclerotic lesions in diabetic patients and in patients with impaired glucose tolerance. In addition to an optimized antidiabetic treatment, statin treatment is inhibitory concerning the development of atherosclerotic lesions.


Lipoprotein lipase mutation S447X associated with pancreatic calcification and steatorrhea in hyperlipidemic pancreatitis.
The factors that whether and how genes involving lipid metabolism including lipoprotein lipase (LPL) and apolipoprotein CII (apo CII) influence occurrence of acute attack of pancreatitis and chronic pancreatitis is not clear. The aim of this study was to determine the association of LPL and apo CII genes with acute attack of pancreatitis and chronic pancreatitis in patients with hyperlipidemic pancreatitis (HLP) and hypertriglyceridemia (HTG). We performed genetic analysis of 134 patients in Taiwan with HTG (53 with HLP and 81 without HLP). The entire coding and intronic regions of the LPL and apo CII genes were identified with heteroduplex analytical techniques or high resolution melting analysis. All mutations were confirmed by sequencing analysis. Correlation of phenotype and genotype was also analyzed. The frequency of LPL gene mutation rates in HLP patients (17.0%, 9 of 53) was significantly higher than that without HLP attack (4.9%, 4 of 81) (P<0.0001). A total of 10.4% (14 of 134) of our HTG patients carried LPL or apo CII mutation. The most common LPL gene mutation was S447X. There is a high prevalence (77.8%) of HLP attack in HTG patients carrying S447X mutation. Multivariate analysis in HLP patients indicated that the presence of LPL mutation and episode of acute attack were independent risks for pancreatic calcification and steatorrhea. This is the first complete genetic study analyzing the association of LPL and apo CII mutation in a HLP population. LPL S447X mutation is associated with a higher risk of pancreatic calcification and steatorrhea than those previously known factors in HLP patients.


Neurological deficit from metastatic low grade liposarcoma.
Myxoid liposarcoma is a malignant soft tissue tumor with a relatively indolent natural history. It commonly occurs in the extremities with extrapulmonary metastatic potential. Round cell liposarcoma, recently, is widely agreed to be the aggressive counterpart of the myxoid liposarcoma, mostly arising in adverse, local recurrence, and metastatic lesions. Metastatic liposarcoma with pure myxoid element is unusual. The authors report an extremely rare case of a 47-year-old Thai male patient having a metastatic pure myxoid liposarcoma to the thoracic vertebrae, one year after primary tumor documented on the left thigh. Histology of the primary and metastatic sites shows only myxoid pattern. Round cell feature was not documented. To the best of the authors' knowledge, this is the second case report of metastatic myxoid liposarcoma without round cell morphology.


Therapeutic advantages of twice-daily over four-times daily inhalation budesonide in the treatment of chronic asthma.
Topical steroid therapy is now widely used in the treatment of chronic asthma, but few controlled studies have been conducted to evaluate the most efficient dosage regimen. The present study was designed to assess, in a double-blind fashion, the relative efficacy of a new topical steroid, budesonide (Pulmicort) in controlling pulmonary function and asthma symptoms during twice-and 4-times daily dosing. Both active and placebo drug were administered via the tube spacer inhaler. Objective lung function measurements indicate that twice-daily dosing is at least as effective as 4-times daily dosing, and it is suggested that the twice-daily dosage regimen may lead to better patient compliance.


[Ritodrine induced pulmonary edema after caesarean section for a triplet pregnancy].
Selective beta-sympathomimetic drugs are frequently used for tocolysis. But, since these drugs exhibit some beta-1 activity as well, they may bring about pulmonary edema, myocardial ischemia, cardiac arrhythmia and others as side effects. A 29 year-old female with a triplet pregnancy had premature contraction at 26 weeks of gestation. High doses of IV ritodrine were given for tocolysis for 8 weeks until caesarean section. One hour after caesarean section at 35 weeks of gestation, she complained of dyspnea. Urinary output decreased and chest X-ray showed pulmonary edema. She was intubated and artificial ventilation with PEEP was performed in ICU. Echocardiogram showed left ventricular dilatation. ECG showed inverted T waves on all leads. We diagnosed her as suffering from acute heart failure, pulmonary edema and acute renal failure. Hemodialysis was performed for 6 hrs but PCWP was still 18 mmHg. So CVVH was added to hemodialysis. Five hrs after the start of CVVH, her symptoms gradually started to subside. Total fluid removal was 5.8 l over 16 hrs. Three days after admission she was extubated and five days later returned to her ward. We concluded that pulmonary edema, heart failure and renal failure were induced by the long-term high dose medication of ritodrine, resulting in volume overload and myocardial dysfunction.


[Abdominal Wall Surgery After SARS-CoV-2: Time to Reestablish Postponed Non-essential Procedures?]
Pandemic by the COVID-19 has found us unprotected to provide an adequate and rapid sanitary response. The hospital network of our public health system has provided most of the resources for the treatment of patients affected by the infection. Non-essential (non-priority) surgeries have been postponed. The optimal and proportionate reestablishment of these non-priority surgeries can be a problem. This article offers a technical and non-technical view of reestablishment non-priority surgeries from the perspective of abdominal wall surgery.


[The influence of corticosteroids on the fibrinolytic activity indifferent tissues of the eye (author's transl)].
The influence of corticosteroids on the fibrinolytic activity in different tissues of the eye was investigated. Rats were treated with corticosteroids, and the fibrinplate method of Todd 1962) was used to estimate the fibrinolytic activity. After 14 days treatment with corticosteroids the fibrinolytic activity decreased. In the control eyes no fibrinolytic activity was left after 6 h of autolysis. The eyes treated with corticosteroids, however, still had fibrinolytic activity.


Fraxinellone.
In the title compound, C(14)H(16)O(3) [systematic name: (3R*,3aR*)-3-(3-furan-yl)-3a,7-dimethyl-3a,4,5,6-tetra-hydro-2-benzofuran-1(3H)-one], the pendant methyl and furan groups attached to the stereogenic centres lie to the same side of the fused ring system. The dihedral angle between the five-membered rings is 74.8 (2)°; the fused five-membered ring adopts a twisted conformation. In the crystal, mol-ecules are linked by weak C-H⋯O inter-actions, which generate [100] chains.


A brief history of Indian alchemy covering pre-Vedic to Vedic and Ayurvedic period (circa 400 B.C.-800 A.D.).
History of Indian alchemy can be traced to pre-Vedic period. The archaeological excavations at Mohenjodaro and Harappa in the Indus valley have brought to light that, the people in ancient India were possessing chemical knowledge as early as in the pre-historic period. In Vedic period single herbs were prescribed. Minerals and animal substances were also prescribed but no compound preparations were in use. Alchemy in India, was started for the preparation of an elixir of life for imparting immortality and later for the transmutation process for converting base metals into gold. Indian alchemy derived its colour and flavour to a large extent from the Tantric cult. Then, during the iatro-chemical period all the previous accumulated alchemical ideas were put into something more practical and tangible. a number of preparations of mercury and other metals were evolved as helpful accessories in medicine. Here a bried history of this Indian alchemy is presented which will give an idea about the development of chemical knowledge in India in its multiple aspects.


Stormwater biofilter treatment model for faecal microorganisms.
This paper presents a new model to simulate long-term microbial removal in stormwater biofilters. The water flow module uses a 'three-bucket' approach to describe the flow processes in biofilters, while the microbial quality module employs the one-dimensional advection-dispersion equation to represent microbial transport and fate under different design and operational conditions. Three governing processes for microbial removal, adsorption, desorption and die-off, are included; temperature is also incorporated as a key factor for die-off. The model was tested using long term monitoring data collected from laboratory columns in which five different biofilter configurations were studied over a period of 44weeks. A multi-objective calibration with the balance of instantaneous ponding levels and event outflow volumes was implemented on the water flow module, and the Nash-Sutcliffe Efficiency (E) values ranged from 0.82 to 0.95. The microbial quality module was tested using the effluent Escherichia coli concentration data, and the E values obtained for different configurations were between 0.46 and 0.68. The optimized parameter values agreed with those presented in literature. However, sensitivity analyses suggested that the model's prediction was not sensitive to all parameters, the explanation for which was hypothesized to be data paucity rather than model structural uncertainties. Model validation was also conducted by splitting the data into calibration and validation datasets. The results further reinforced the needed for more data for model calibration.


Perspective: Photocatalytic reduction of CO2 to solar fuels over semiconductors.
Increasing emissions of carbon dioxide and the depletion of finite fossil fuels have led to many concerns about global warming and energy crises. Consequently, a sustainable and alternative method, photocatalytic CO2 reduction to chemical fuels has received considerable attention. This perspective highlights recent knowledge and the main challenges in CO2 photoreduction primarily from the theoretical field. The fundamental understanding of CO2 adsorption and reaction mechanism at an atomic level is fully addressed, and the relevant effects dominating the process of CO2 photoreduction are also elucidated. Moreover, recent development of photocatalysts including structural modification is presented, which greatly affects the efficiency and selectivity of CO2 conversion. Finally, the possibilities and challenges in this field are discussed.


Exploring the iceberg of hypertension: a community based study in an eastern Nepal town.
Hypertension is an important public health challenge in the developing and the developed world alike. However, community-based studies on cardiovascular diseases including hypertension in a developing country like Nepal have been limited. The primary aim of this study is to measure the prevalence of hypertension in the Dharan town of Eastern Nepal and to explore the 'iceberg phenomenon' of hypertension in the study population. A population-based cross-sectional analytical study was undertaken in the Dharan municipality in 2004-5 with one thousand males aged 35 years and above as participants. The subjects were recruited by simple random sampling of the households in each ward. The overall prevalence of hypertension in the study population was 22.7% which was comparable to the studies from Northern and Western India. The comparison between the population with normal and high blood pressure at time of study shows significant differences in terms of age, religion, current job status, occupation, socio-economic status, physical activity and tobacco use. The study shows that while a vast majority of the hypertensive population was not aware of their high blood pressure status, at the same time, a large fraction of the population with increased blood pressure did not have their blood pressure under control. A surveillance system to detect population with high blood pressure, follow up the detected cases of hypertension, as well as motivate and/or counsel the 'hard-to-treat' cases for regular follow-up should be valuable.


Graphene oxide encapsulated forsterite scaffolds to improve mechanical properties and antibacterial behavior.
It is very desirable to have good antibacterial properties and mechanical properties at the same time for bone scaffolds. Graphene oxide (GO) can increase the mechanical properties and antibacterial performance, while forsterite (Mg2SiO4) as the matrix can increase forsterite/GO scaffolds' biological activity for bone tissue engineering. Interconnected porous forsterite scaffolds were developed by space holder processes for bone tissue engineering in this research. The forsterite/GO scaffolds had a porosity of 76%-78% with pore size of 300-450 μm. The mechanism of the mechanical strengthening, antibacterial activity, and cellular function of the forsterite/GO scaffold was evaluated. The findings show that the compressive strength of forsterite/1 wt.% GO scaffold (2.4 ± 0.1 MPa) was significantly increased, in comparison to forsterite scaffolds without GO (1.4 ± 0.1 MPa). Validation of the samples' bioactivity was attained by forming a hydroxyapatite layer on the forsterite/GO surface withinin vitroimmersion test. The results of cell viability demonstrated that synthesized forsterite scaffolds with low GO did not show cytotoxicity and enhanced cell proliferation. Antibacterial tests showed that the antibacterial influence of forsterite/GO scaffold was strongly correlated with GO concentration from 0.5 to 2 wt.%. The scaffold encapsulated with 2 wt.% GO had the great antibacterial performance with bacterial inhibition rate around 90%. As results show, the produced forsterite/1 wt.% GO can be an attractive option for bone tissue engineering.


Carotid endoarterectomy in the presence of contralateral carotid occlusion.
The purpose of this study was to define a correct anesthesiological and surgical approach in patient who present a significant carotid stenosis with contralateral carotid occlusion. Between 1996 and 1998 in our Department of Vascular Surgery of the Hospital S. Giovanni Battista has been executed 337 Carotid Endoarterectomies (CEA). Of these, 44 patient (13%) had a contralateral internal carotid occlusion. Forty was male (91%), and 4 female (9%). Echo Doppler, angiography, angioTC or angio-RMN and TCD were performed in all patients. In all cases was executed a traditional CEA. Because of the presence of a large ischaemic cerebral lesion or clamping intolerance 12 operation were performed under general anesthesia (27%). Shunt was used in 15 patients (34%) and patch was used in 10 cases (23%). In 2 cases (4.5%) there was be a thrombosis of the operated internal carotid artery and one patient died (2.3%). The presence of contralateral internal carotid occlusion with carotid stenosis > 70% increase the risk of peroperative stroke because of the difficulty of collateral cerebral blood flow. The execution of echo Doppler, angiography, angioTC or angioRM and TCD and their evaluation permit to choice the best anesthesiological and surgical treatment. The utilization of narcosis with thiopental protection and shunting reducing the rate of perioperative stroke, but the local anesthesia allows the best monitoring of intraoperative cerebral function. This behaviour was correctly when in patient with contralateral internal carotid occlusion there is an insufficient intracranic vascularization or an extensive ischaemic lesion or clamping intolerance.


New developments in the treatment algorithm for peripheral neuropathic pain.
Neuropathic pain often imposes a substantial and unrelenting burden on those individuals who have it; single-agent analgesics typically only reduce pain at best. Worldwide, five sets of treatment recommendations offer insight into managing neuropathic pain, including two European guidelines, one Canadian, one Latin American, and another constructed under the auspices of the International Association for the Study of Pain (IASP). The analgesics common to these guidelines are topical lidocaine, secondary amine tricyclic antidepressants, serotonin and norepinephrine dual reuptake inhibitors, calcium channel α(2)-δ ligands, tramadol, and opioid antagonists. Still, significant knowledge gaps in the treatment of neuropathic pain conditions have hampered the development of algorithms and multimodal approaches. As the evidence base expands, the addition of new comparative trial data will further refine the development of new guidance for clinical management of neuropathic pain. New alternatives for managing neuropathic pain, such as the high-concentration capsaicin patch, will enlarge the treatment armamentarium and potentially impact therapeutic guidelines.


2D image of local density and magnetic fluctuations from line-integrated interferometry-polarimetry measurements.
Combined polarimetry-interferometry capability permits simultaneous measurement of line-integrated density and Faraday effect with fast time response (∼1 μs) and high sensitivity. Faraday effect fluctuations with phase shift of order 0.05° associated with global tearing modes are resolved with an uncertainty ∼0.01°. For physics investigations, local density fluctuations are obtained by inverting the line-integrated interferometry data. The local magnetic and current density fluctuations are then reconstructed using a parameterized fit of the polarimetry data. Reconstructed 2D images of density and magnetic field fluctuations in a poloidal cross section exhibit significantly different spatial structure. Combined with their relative phase, the magnetic-fluctuation-induced particle transport flux and its spatial distribution are resolved.


Determining the structure of L-arginine and other organic molecules.
The time is now: Very real opportunities that now exist for determining the crystal structures of organic molecules using sophisticated techniques for the analysis of powder X-ray diffraction data are highlighted herein. The application of these techniques has recently led to the first crystal structure determination reported for L-arginine.


Involvement of Mitochondrial Activity and OXPHOS in ATP Synthesis During the Motility Phase of Spermatozoa in the Pacific Oyster, Crassostrea gigas.
In the Pacific oyster, spermatozoa are characterized by a remarkably long movement phase (i.e., over 24 h) sustained by a capacity to maintain intracellular ATP level. To gain information on oxidative phosphorylation (OXPHOS) functionality during the motility phase of Pacific oyster spermatozoa, we studied 1) changes in spermatozoal mitochondrial activity, that is, mitochondrial membrane potential (MMP), and intracellular ATP content in relation to motion parameters and 2) the involvement of OXPHOS for spermatozoal movement using carbonyl cyanide m-chlorophenyl hydrazone (CCCP). The percentage of motile spermatozoa decreased over a 24 h movement period. MMP increased steadily during the first 9 h of the movement phase and was subsequently maintained at a constant level. Conversely, spermatozoal ATP content decreased steadily during the first 9 h postactivation and was maintained at this level during the following hours of the movement phase. When OXPHOS was decoupled by CCCP, the movement of spermatozoa was maintained 2 h and totally stopped after 4 h of incubation, whereas spermatozoa were still motile in the control after 4 h. Our results suggest that the ATP sustaining flagellar movement of spermatozoa may partially originate from glycolysis or from mobilization of stored ATP or from potential phosphagens during the first 2 h of movement as deduced by the decoupling by CCCP of OXPHOS. However, OXPHOS is required to sustain the long motility phase of Pacific oyster spermatozoa. In addition, spermatozoa may hydrolyze intracellular ATP content during the early part of the movement phase, stimulating mitochondrial activity. This stimulation seems to be involved in sustaining a high ATP level until the end of the motility phase.


Refsum's disease: electron microscopy of an iris biopsy.
Refsum's disease (phytanic acid storage disease) results in an accumulation of lipid as a result of an absence of mitochondrial hydroxylation of phytanic acid. We describe a previously unrecorded electron microscopic study of lipid deposition in the iris pigment epithelium of a patient with Refsum's disease, and lipid was present in other sites within the iris.


Geographic miss of lung tumours due to respiratory motion: a comparison of 3D vs 4D PET/CT defined target volumes.
PET/CT scans acquired in the radiotherapy treatment position are typically performed without compensating for respiratory motion. The purpose of this study was to investigate geographic miss of lung tumours due to respiratory motion for target volumes defined on a standard 3D-PET/CT. 29 patients staged for pulmonary malignancy who completed both a 3D-PET/CT and 4D-PET/CT were included. A 3D-Gross Tumour Volume (GTV) was defined on the standard whole body PET/CT scan. Subsequently a 4D-GTV was defined on a 4D-PET/CT MIP. A 5 mm, 10 mm, 15 mm symmetrical and 15×10 mm asymmetrical Planning Target Volume (PTV) was created by expanding the 3D-GTV and 4D-GTV's. A 3D conformal plan was generated and calculated to cover the 3D-PTV. The 3D plan was transferred to the 4D-PTV and analysed for geographic miss. Three types of miss were measured. Type 1: any part of the 4D-GTV outside the 3D-PTV. Type 2: any part of the 4D-PTV outside the 3D-PTV. Type 3: any part of the 4D-PTV receiving less than 95% of the prescribed dose. The lesion motion was measured to look at the association between lesion motion and geographic miss. When a standard 15 mm or asymmetrical PTV margin was used there were 1/29 (3%) Type 1 misses. This increased 7/29 (24%) for the 10 mm margin and 23/29 (79%) for a 5 mm margin. All patients for all margins had a Type 2 geographic miss. There was a Type 3 miss in 25 out of 29 cases in the 5, 10, and 15 mm PTV margin groups. The asymmetrical margin had one additional Type 3 miss. Pearson analysis showed a correlation (p < 0.01) between lesion motion and the severity of the different types of geographic miss. Without any form of motion suppression, the current standard of a 3D- PET/CT and 15 mm PTV margin employed for lung lesions has an increasing risk of significant geographic miss when tumour motion increases. Use of smaller asymmetric margins in the cranio-caudal direction does not comprise tumour coverage. Reducing PTV margins for volumes defined on 3D-PET/CT will greatly increase the chance and severity of a geometric miss due to respiratory motion. 4D-imaging reduces the risk of geographic miss across the population of tumour sizes and magnitude of motion investigated in the study.


Enhancing obSTORM imaging performance with cubic spline PSF modeling.
Oblique plane microscopy-based single molecule localization microscopy (obSTORM) has shown great potential for super-resolution imaging of thick biological specimens. Despite its compatibility with tissues and small animals, prior uses of the Gaussian point spread function (PSF) model have resulted in limited imaging resolution and a narrow axial localization range. This is due to the poor fit of the Gaussian PSF model with the actual PSF shapes in obSTORM. To overcome these limitations, we have employed cubic splines for a more accurate modeling of the experimental PSF shapes. This refined PSF model enhances three-dimensional localization precision, leading to significant improvements in obSTORM imaging of mouse retina tissues, such as an approximately 1.2 times increase in imaging resolution, seamless stitching of single molecules between adjacent optical sections, and a doubling of the sectional interval in volumetric obSTORM imaging due to the extended axial range of usable section thickness. The cubic spline PSF model thus offers a path towards more accurate and faster volumetric obSTORM imaging of biological specimens.