Vibratory and plantar pressure stimulation: Steps to improve freezing of gait in Parkinson's disease.
Freezing of gait (FOG) is a devastating symptom that develops in patients with advanced Parkinson's disease (PD) and is often unresponsive to pharmacological treatment. Recent research suggests that FOG may result from dysfunctional plantar peripheral sensory systems. The impact of combined plantar pressure and vibratory stimulation over vibratory or pressure alone on FOG remains unexplored. PD patients with FOG were randomised into four groups and treated with combined vibratory and pressure stimulation, vibratory stimulation alone, pressure stimulation alone, or controls (no stimulation). Vibratory stimulation targeted both Achilles' tendons. Simultaneous bilateral pressure stimulation was applied to the first hallux, first metatarsal bone, and the sole. The primary outcome included normalized percent changes in percent FOG measured both pre- and immediately post-stimulation. Other outcomes including clinical rating scale, response to questionnaires, number and duration of freezing episodes, and spatiotemporal gait parameters at pre- and freezing episodes were also explored. Sixty PD patients participated in the study. Patients who were treated with combined vibratory and pressure stimulation responded with significant decreases in normalized percent changes of percent FOG (62.75 ± 25.54%, p < 0.001) compared with those treated with vibration alone (11.38 ± 8.29%, p < 0.001), pressure alone (15.15 ± 16.18%, p < 0.001), or controls (8.59 ± 16.85%, p < 0.001). Our study demonstrated the benefit of combined vibratory and pressure stimulation on FOG suggesting that this strategy might be developed as a novel treatment modality for PD patients with FOG.


Noradrenaline axon terminals in adult rat neocortex: an immunocytochemical analysis in serial thin sections.
Peroxidase-antiperoxidase electron microscope immunocytochemistry with an antiserum against noradrenaline-glutaraldehyde-protein conjugate was used to identify cortical noradrenaline terminals (axonal varicosities) from the upper layers of the frontal, parietal and occipital cortex in adult rat. A large number of immunostained varicosities were examined in serial thin sections, and compared with a control population of randomly chosen unlabeled terminals from the same sections. Both groups of varicosities were measured and scrutinized for the presence of a junctional complex indicative of synaptic specialization. Cellular elements juxtaposed to the membrane of both types of varicosities were also identified and counted. Noradrenaline varicosities in all three cortical regions averaged 0.65 microns in diameter. In contrast to their unlabeled counterparts, these profiles rarely showed a membrane differentiation characteristic of a synaptic contact (junctional complex). The rare junctional complexes formed by cortical noradrenaline varicosities were invariably symmetrical and almost always found on dendritic shafts. The microenvironment of noradrenaline varicosities also differed, exhibiting a greater number of apposed axonal varicosities and a smaller number of dendritic spines than that of the random population. The proportion of noradrenaline varicosities making a synaptic contact (synaptic incidence) was determined by plotting the incidence of visible junctions as a function of the number of thin sections available for examination. As extrapolated for whole varicosities after linear transformation (double reciprocal plot), this proportion was 17% or 26% depending on the stringency of the criteria used in identifying the junctional complex. The same analysis provided a figure of 98% for the control population. The present study largely confirmed our initial radioautographic characterization of the cortical noradrenaline innervation as a mostly non-junctional system, and also indicated that these varicosities are set in a particular microenvironment. These new data further support the eventuality of a diffuse release of cortical noradrenaline in the extracellular space, compatible with both its neuromodulatory role and multiplicity of actions on diverse cellular targets in the cerebral cortex. The functions assigned to the coeruleocortical noradrenaline system must therefore be viewed as the product of a widespread and ubiquitously distributed neuronal organization characterized by loose intercellular relationships. This system might be capable of selectivity and specificity of action, however, owing to the distribution of its receptors, and in view of intrinsically or extrinsically driven control mechanisms triggered by the release of its own or other transmitters and which may also involve target-initiated feedback mechanisms.


Typical carcinoid involving the main carina managed with arterial embolisation, endobronchial resection and ablation, ultimately followed by carinal resection.
Bronchial carcinoids are uncommon pulmonary tumours, and the gold standard management is surgical resection. Their management is often complicated by their proximal location and propensity to bleed when manipulated. A 22-year-old man was found to have typical carcinoid tumour involving the carina and surgical resection was considered not feasible. We report our experience with a multimodality approach involving arterial embolisation, with subsequent endobronchial resection and ablation. Residual disease was found and managed with definitive carinal resection.


Population-based references for waist and hip circumferences, waist-to-hip and waist-to-height ratios for children and adolescents, and evaluation of their predictive ability.
Childhood obesity is a public health problem globally as well as in Poland. This paper aimed to provide age- and sex-specific waist circumference, hip circumference, waist-to-height ratio and waist-to-hip ratio normative values for Polish children and adolescents aged 3 - 18 years for more precise monitoring of abdominal fat accumulation. The waist circumference, hip circumference, waist-to-height ratio and waist-to-hip ratio references were constructed with the lambda-mu-sigma (LMS) method using data from two nationally representative health surveys: the OLA study and the OLAF study, the largest available paediatric surveys in Poland which provided measured height, weight, waist, hip and blood pressure for 22,370 children and adolescents aged 3 - 18 years. The predictive ability of newly established references for overweight/obesity as defined by the International Obesity Task Force criteria and elevated blood pressure was tested with receiver operating characteristic. Abdominal obesity cut-offs linked to adult cardiometabolic cut-offs were established. Reference values for waist circumference, hip circumference, waist-to-height ratio and waist-to-hip ratio are presented, as well as waist circumference, waist-to-height ratio and waist-to-hip ratio cut-off values linked to adult's cut-offs of cardiometabolic risk. The predictive value for overweight and obesity of population-based waist, hip and waist-to-height ratio references was outstanding-area under the receiver operating characteristic curve > 0.95 in both sexes, whereas with regard to the elevated blood pressure predictive ability was low-area under the receiver operating characteristic curve < 0.65. Conclusion: This paper presents the first waist, hip, waist-to-height ratio and waist-to-hip ratio references for Polish children and adolescents aged 3-18 years. The 90th and 95th percentile and cut-offs linked to adult thresholds for cardiometabolic risk are proposed as cut-offs for abdominal obesity. What is Known: • Waist circumference, waist-to-height ratio and waist-to-hip ratio are used to assess abdominal obesity in children and adults. • In Poland, there is no abdominal obesity and hip circumference references for children and adolescents from 3 to 18 years of age. What is New: • Population-based references of central obesity indices and hip references for children and youth aged 3-18 years and cardiometabolic risk thresholds for children and adolescents linked to adult's cut-offs were established.


The Interaction Effect of Parental Rejection and Oxytocin Receptor Gene Polymorphism on Depression: A Cross-Cultural Study in Non-Clinical Samples.
Parental rejection has been consistently empirically implicated in a wide array of developmental, behavioural and psychological problems worldwide. However, the interaction effect between parental rejection in childhood and the oxytocin receptor genotype on psychological adjustment has yet to be investigated. The present study aimed to investigate gene-environment interaction effects between parental rejection (maternal and paternal) and oxytocin receptor (OXTR) gene polymorphisms (rs53576 and rs2254298) on depressive symptoms in adults in different cultural contexts. Adults from Italy and Japan (N = 133, age = 18-27 years, females = 68) were preliminarily genotyped and then completed the Parental Acceptance-Rejection Questionnaire for mothers and fathers and the Beck Depression Inventory. Hierarchical multiple regression analysis showed that paternal rejection was related to self-reported depression and that the effect of parental rejection was moderated by OXTR gene polymorphisms and nationality. Among Italians, OXTR rs2254298 A-carriers showed resilience to negative early parental care, whereas among Japanese, OXTR rs53576 non-A-carriers showed resistance to negative early paternal care. These findings align with expected relations between perceived acceptance-rejection and an individual's psychological adjustment, as proposed by interpersonal acceptance-rejection theory, and indicate the need for future studies adopting a multicultural and multilevel approach to better understand how the effects of parental rejection extend into adulthood.


Performance degradation and damage model of rice husk ash concrete under dry-wet cycles of sulfate environment.
Rice husk ash concrete (RHAC) is a new type of concrete that has been rapidly gaining acceptance in recent years. In this paper, the improvement effect of rice husk ash (RHA) on the sulfate erosion performance of concrete was confirmed. The ratio of rice husk ash concrete (RHAC) was optimized and compared with ordinary concrete (OC). The performance degradation of 9%RHAC (rice husk ash at 9% by weight of cement) and OC within 135 times erosion dry-wet cycles solution with Na2SO4 at 5% by weight of solution were studied, including the change of apparent phenomena, compressive strength, tensile strength, effective porosity, and dynamic elastic modulus. The microstructure changes of samples before and after sulfate dry-wet cycle were observed by using a scanning electron microscope (SEM). The results show that with the increase of sulfate dry-wet cycle times, the concrete specimen gradually peels off and expands in volume. The compressive strength and tensile strength increase first and then drop sharply, the effective porosity decreases first and then increases, and the relative dynamic elastic modulus increases and then decreases. The reason is that the ettringite and gypsum are formed by the reaction of sulfate intrusion and hydration products under wetting treatment. After drying treatment, ettringite and free water combine to form sodium sulfate. In the early of circulation, ettringite, gypsum, and sodium sulfate fill the internal pores of the concrete and improve the density. As the number of sulfate dry-wet cycles increases, expansion products accumulate, causing structural expansion damage and deterioration of mechanical performance. However, the hydrated calcium silicate hydrate gel was produced by mixing rice husk ash with concrete to improve the material strength and corrosion resistance. The deterioration degree of the 9%RHAC is better than that of OC at all stages. Finally, the damage constitutive models were established, and the accuracy is higher compared with the measured value.


Plumbagin improves the efficacy of androgen deprivation therapy in prostate cancer: A pre-clinical study.
Plumbagin is a candidate drug for the treatment of prostate cancer. Previous observations indicated that it may improve the efficacy of androgen deprivation therapy (ADT). This study evaluates the effectiveness of treatment with combinations of plumbagin and alternative strategies for ADT in mouse models of prostate cancer to support its clinical use. Plumbagin was administered per oral in a new sesame oil formulation. Standard toxicology studies were performed in rats. For tumor growth studies, mouse prostate cancer cell spheroids were placed on top of grafted prostate tissue in a dorsal chamber and allowed to form tumors. Mice were separated in various treatment groups and tumor size was measured over time by intra-vital microscopy. Survival studies were done in mice after injection of prostate cancer cells in the prostate of male animals. Androgen receptor (AR) levels were analyzed by Western blot from prostate cancer cells treated with plumbagin. Plumbagin caused a decrease in AR levels in vitro. In mice, plumbagin at 1 mg/kg in sesame oil displayed low toxicity and caused a 50% tumor regression when combined with castration. The combination of plumbagin with various forms of chemical ADT including treatment with a GnRH receptor agonist, a GnRH receptor antagonist, or CYP17A1 inhibitors, outperformed ADT alone, increasing mouse survival compared to the standard regimen of castration alone. In contrast, the combination of plumbagin with AR antagonists, such as bicalutamide and enzalutamide, showed no improvement over AR antagonists alone. Thus, plumbagin is effective in combination with drugs that prevent the synthesis of testosterone or its conversion to dihydrotestosterone, but not with drugs that bind to AR. Plumbagin significantly improves the effect of ADT drugs currently used in the clinic, with few side effects in mice.


Isotype-specific detection of ABO blood group antibodies using a novel flow cytometric method.
Several methods to detect anti-A/B antibodies based on haemagglutination and haemolysis have been described. These methods measure predominantly anti-A/B immunoglobulin (Ig)M, whereas anti-A/B IgG and IgG subclasses are less well examined. We established a flow cytometry method (ABO-fluorescence-activated cell sorting; ABO-FACS) to quantify binding of anti-A/B IgM, IgG and IgG subclasses to human A or B red blood cells. Anti-A/B IgM were present in the majority of 120 blood donors, as expected from blood group typing. The sensitivity and specificity of anti-A/B IgM to predict the blood group was 93% and 96% respectively. Anti-A/B IgG was found in 34/38 blood group O samples (89%). Anti-B IgG in blood group A or anti-A IgG in blood group B was present in 4/28 (14%) and 1/28 (4%) samples, respectively, and absent in 26 AB sera. IgG2 was the predominant IgG subclass. The correlation of anti-A/B IgM and IgG in the ABO-FACS with haemagglutination titres was 0.870 and 0.783, respectively (n = 240; P < 0.001) whereas the comparison of ABO-FACS with ABO-enzyme-linked immunosorbent assay was less significant. In conclusion, ABO-FACS is a valid method to quantify anti-A/B IgM, IgG and IgG subclasses. It opens the possibility of isotype-specific monitoring of anti-A/B antibodies levels after ABO-incompatible solid organ and stem cell transplantation.


Stability of nanosuspensions in drug delivery.
Nanosuspensions are nanosized colloidal dispersion systems that are stabilized by surfactants and/or polymers. Because nanosizing results in the creation of new interfaces and in a positive Gibbs free energy change, nanosuspensions are thermodynamically unstable systems with a tendency toward agglomeration or crystal growth. Despite extensive research on nanosuspension technology, stability remains a limitation for pharmaceutical or industrial applications of nanosuspensions. Furthermore, the empirical relationship between stabilizer efficacy and nanosuspension stability has not been well characterized. This review focuses on the issue of nanosuspension stability in drug delivery to present the state of the art of nanosuspensions. Therefore, this review will discuss unstable suspensions, methods and guidelines for selecting and optimizing stabilizers, approaches for enhancing stability, and other factors that influence nanosuspension stability. This review could serve as a reference for the educated selection of a stabilizer for a specific drug candidate and the optimization of the operational parameters for nanosuspension formulation, rather than the currently practiced trial-and-error approach.


Surgical targets for dystonic tremor: considerations between the globus pallidus and ventral intermediate thalamic nucleus.
Dystonic tremor (DT) is characterized by coexisting tremor and abnormal dystonic posturing in the same segment. DT is often medically refractory and DBS is an important therapeutic option. However, the optimal surgical target for DT remains uncertain with Vim, GPi and zona incerta previously reported as effective. We retrospectively reviewed the outcome data from all patients with DT involving at least one upper extremity who underwent DBS at Vanderbilt University from July 2006 to July 2010. We evaluated the improvement of tremor and dystonia after their response to DBS was judged to be maximal. Ten patients met the inclusion criteria. Vim was targeted in four patients and three had unilateral procedure and one bilateral Vim DBS. GPi was targeted in four patients with bilateral DBS procedure in every patient from this subgroup. A combined bilateral GPi and unilateral Vim DBS was performed in two patients. The best results for tremor control were observed in patients with Vim DBS but they had persisting mild dystonia. Patients with GPi DBS had average DT improvement by approximately 50% but their dystonia symptoms were markedly improved. We propose that the patients with DT with a mild dystonia should be considered for Vim DBS procedure and the coexistence of severe DT and dystonia may be successfully controlled by combined GPi and Vim DBS surgeries.


The Use of the Selective Imidazoline I1 Receptor Agonist Carbophenyline as a Strategy for Neuropathic Pain Relief: Preclinical Evaluation in a Mouse Model of Oxaliplatin-Induced Neurotoxicity.
Anti-cancer therapy based on the repeated administration of oxaliplatin is limited by the development of a disabling neuropathic syndrome with detrimental effects on the patient's quality of life. The lack of effective pharmacological approaches calls for the identification of innovative therapeutic strategies based on new targets. We focused our attention on the imidazoline I1 receptor (I1-R) and in particular on the selective I1-R agonist 2-(1-([1,1'-biphenyl]-2-yl)propan-2-yl)-4,5-dihydro-1H-imidazole) (carbophenyline). The purpose of this work was the preclinical evaluation of the efficacy of carbophenyline on oxaliplatin-induced neuropathic pain in mice. Carbophenyline, acutely per os administered (0.1-10 mg kg-1), induced a dose-dependent anti-hyperalgesic effect that was completely blocked by the pre-treatment with the I1-R antagonist 3 or the I1/α2 receptor antagonist efaroxan, confirming the I1-R-dependent mechanism. Conversely, pre-treatment with the I2-R antagonist BU224 did not block the anti-nociceptive effect evoked by carbophenyline. Repeated oral administrations of carbophenyline (1 mg kg-1) for 14 days, starting from the first day of oxaliplatin injection, counteracted the development of neuropathic pain in all behavioral tests (cold plate, Von Frey, and paw pressure tests) carried out 24 h after the last carbophenyline treatment on days 7 and 14. In the dorsal horn of the spinal cord, carbophenyline significantly decreased the oxaliplatin-induced astrocyte activation detected by immunofluorescence staining by the specific labelling with GFAP antibody. In conclusion, carbophenyline showed anti-neuropathic properties both after acute and chronic treatment with preventive effect against oxaliplatin-induced astrocyte activation in the spinal cord. Therefore, I1-R agonists emerge as a new class of candidates for the management of oxaliplatin-induced neuropathic pain.


Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Evaluation and Treatment of Patients with Thoracolumbar Spine Trauma: Operative Versus Nonoperative Treatment.
Does the surgical treatment of burst fractures of the thoracic and lumbar spine improve clinical outcomes compared to nonoperative treatment? There is conflicting evidence to recommend for or against the use of surgical intervention to improve clinical outcomes in patients with thoracolumbar burst fracture who are neurologically intact. Therefore, it is recommended that the discretion of the treating provider be used to determine if the presenting thoracic or lumbar burst fracture in the neurologically intact patient warrants surgical intervention. Strength of Recommendation: Grade Insufficient. Does the surgical treatment of nonburst fractures of the thoracic and lumbar spine improve clinical outcomes compared to nonoperative treatment? There is insufficient evidence to recommend for or against the use of surgical intervention for nonburst thoracic or lumbar fractures. It is recommended that the decision to pursue surgery for such fractures be at the discretion of the treating physician. Strength of Recommendation: Grade Insufficient The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_1.


A new approach to image subtraction in immunoscintigraphy: preliminary results.
Recently proposed image comparison software is applied to immunoscintigraphy. The software performs geometric and gray level registration of two images and generates an image of the statistically significant differences. It permits the comparison of scintigraphic images recorded at different times. It is used to subtract 113mIn and 111Inphytate colloid liver scans and early (blood pool) images from 131I or 111In-monoclonal Ab images and to compare Ab images recorded at different times. Using the procedures made possible by this software, only images recorded using the same radionuclide or using radionuclides of about the same energy are compared. Anti CEA, 19-9 and OC 125 F(ab)2 fragments labeled with 131I or 111In are used in 32 patients with 47 demonstrated recurrences or metastases of colorectal or ovarian cancers. The overall sensitivities of the unprocessed and processed images are 25/47 and 41/47 respectively. The improvement in sensitivity is particularly high in the liver when In labelled Ab are used. This technique improves the contrast of the images, but the interpretation must take into account the components of the non target activity (kidney, bone marrow, colon...) which are not removed by the image subtraction method.


Recent developments in the prevention and treatment of congenital toxoplasmosis.
The manifestations of congenital toxoplasmosis vary considerably in degree, characteristics and time of onset. Options for prevention of the disease include the appropriate disposal of cat litter and the avoidance of ingestion of both contaminated food and undercooked meat by pregnant women. Immunisation of the domestic cat population is a consideration for the future. Alternatively, immunisation of sero-negative pregnant women awaits the introduction of an effective and safe reagent. Current treatment modalities are not universally effective and new drugs are the subject of active development and research. Screening of pregnant women or perhaps newborn infants are potential options but the cost effectivity has yet to be established in many countries and the results of treatment during pregnancy and early childhood are encouraging but are as yet unproven. The majority of patients with congenital toxoplasmosis eventually develop toxoplasmic retinochoroiditis. Current treatment options for this condition are outlined. Acquired immune deficiency syndrome (AIDS) may, in some cases, represent a recrudescence of congenital intracerebral infection. Current treatment strategies for this condition are discussed.


Influence of leucine and valine on ramoplanin production by Actinoplanes sp. ATCC 33076.
Ramoplanin is a glycolipodepsipeptide antibiotic obtained by fermentation of the Actinoplanes sp. ATCC 33076, isolated as a complex of three closely related components A1, A2 and A3, which differ in their fatty acid moiety. We have investigated the influence of L-leucine and L-valine, the biosynthetic precursors of the fatty acids in A2 and A3 factors, on the complex composition and antibiotic productivity. Addition of 5 g/litre of L-leucine at the time of inoculation increases antibiotic production and improves the production of A2 factor, which represents the active principle component under clinical development. Addition of L-valine in the same conditions modifies the composition of the complex towards the A3 factor but does not improve total antibiotic productivity. A possible explanation for the different actions of the two amino acids is presented.


Direct LSC method for measurements of biofuels in fuel.
Direct liquid scintillation counting (LSC) for quantification of biofuels content in fuels was implemented and validated on three liquid fossil fuel matrices-ethanol, gasoline and diesel. Fatty acid methyl esters (FAMEs), hydrogenated vegetable oils (HVO) and bio-ethanol were used as biofuels. The method is applicable in the range up to 100% for all tested combinations of bio components. The sensitivity and precision of the method are suitable for determination of bio component content in the blends which is appearing on the global market. The method does not require special equipment for sample preparation.


Neurological symptoms as a clinical manifestation of coronavirus disease 2019: implications for internists.
Numerous experimental and clinical studies have proven that the new severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) has a tropism for the nervous system. The infection of the nervous system by SARS‑CoV‑2 can occur via the nasal route through trans‑synaptic pathways. Coronaviruses can infect neurons and glial cells through angiotensin‑converting enzyme 2 receptors or by endocytosis. The infection of the central nervous system accompanied by coronavirus disease 2019-related systemic inflammation leads to the impairment of the blood-brain barrier and triggers a neuroinflammatory response with reactive astrogliosis and microglial activation. In addition, brain stem cells are being damaged, which results in respiratory distress. Apart from typical symptoms of COVID‑19 associated with the involvement of the respiratory system, neurological manifestations such as headache, dizziness, myalgia, anosmia, ageusia, encephalopathy, encephalitis, stroke, epileptic seizures, rhabdomyolysis, and Guillain-Barré syndrome are related to SARS‑CoV‑2 infection. In this review, we focused on the currently known neurological manifestations of COVID‑19, which could be considered mainly in asymptomatic patients with COVID‑19 and, if noted, may limit the transmission of coronavirus infection.


Clinical assessment of delayed gastric emptying and diabetic complications using gastric emptying scintigraphy: involvement of vascular disorder.
Delayed gastric emptying, including gastroparesis, is a common complication in diabetes mellitus. The association between delayed gastric emptying and overall diabetic complications remains to be studied in detail. We analysed this association. We performed gastric emptying scintigraphy of (99m) Tc-diethylenetriaminepentaacetic acid in 34 patients with diabetes to measure the gastric emptying half-times (T1/2) of the whole stomach (WS), proximal stomach (PS) and distal stomach (DS). We assessed T1/2, diabetic-related factors and complications. The prevalence of autonomic neuropathy was higher in the group with delayed T1/2 of the WS than in the normal group. Analysis of intima-media thickness (IMT) and ankle brachial pressure index (ABI), which are risk indicators for vascular disorder, showed that IMT of the carotid bulb was greater in the group with delayed T1/2 of the WS than in the normal group (2·41 mm [1·50-2·81] versus 1·40 mm [0·81-2·08], P = 0·015). T1/2 of the WS correlated positively with IMT of the carotid bulb (r = 0·391, P = 0·027) and negatively with ABI (r = -0·389, P = 0·028). These correlations were mainly attributed to PS and were the same in patients without autonomic neuropathy. In seven of nine patients who received scintigraphy again after diabetic treatment, glycosylated haemoglobin (HbA1c) levels decreased and T1/2 of the WS shortened compared with before treatment. Vascular disorder, among other cofactors such as autonomic neuropathy, could be involved in the pathophysiology of delayed gastric emptying. Medium- to long-term glycaemic control was associated with gastric emptying.


Synthesis of i-Corona[6]arenes for Selective Anion Binding: Interdependent and Synergistic Anion-π and Hydrogen-Bond Interactions.
i-Corona[3]arene[3]tetrazines were synthesized from the nucleophilic aromatic substitution reaction of resorcinol and its derivatives with 3,6-dichlorotetrazine in a one-pot fashion under mild conditions. All of the resulting macrocycles adopted 1,3,5-alternate conformation irrespective of the nature of the substituents on both upper- and lower-rims. i-Corona[3]arene[3]tetrazine was found to self-regulate its macrocyclic conformation and cavity to recognize anions with binding constants spanning from 26 M-1 to 2.2×103 M-1 depending on the structure of the anions. The selective binding resulted from a significant interdependent and synergistic effect between multiple tetrazine π/anion and Caryl -H/anion hydrogen bond interactions. Taking advantage of synergistic effect revealed, a cyanobenzene-embedded i-corona[3]arene[3]tetrazine was designedly synthesized and highly selective and very strong affinity toward nitrate with a binding constant of 2.2×105 M-1 was achieved.


C-reactive protein (CRP) trajectory as a predictor of anastomotic leakage after rectal cancer resection: A multicentre cohort study.
This study aimed to identify whether CRP-trajectory measurement, including increase in CRP-level of 50 mg/l per day, is an accurate predictor of anastomotic leakage (AL) in patients undergoing resection for rectal cancer. A prospective multicentre database was used. CRP was recorded on the first three postoperative days. Sensitivity, specificity, positive and negative predictive values, and area under the receiver operator characteristic (ROC) curve were used to analyse performances of CRP-trajectory measurements between postoperative day (POD) 1-2, 2-3, 1-3 and between any two days. A total of 271 patients were included in the study. AL was observed in 12.5% (34/271). Increase in CRP-level of 50 mg/l between POD 1-2 had a negative predictive value of 0.92, specificity of 0.71 and sensitivity of 0.57. Changes in CRP-levels between POD 2-3 were associated with a negative predictive value, specificity and sensitivity of 0.89, 0.93 and 0.26, respectively. Changes in CRP-levels between POD 1-3 showed a negative predictive value of 0.94, specificity of 0.76 and sensitivity of 0.65. In addition, 50 mg/l changes between any two days showed a negative predictive value of 0.92, specificity of 0.66 and sensitivity of 0.62. The area under the ROC curve for all CRP-trajectory measurements ranged from 0.593-0.700. The present study showed that CRP-trajectory between postoperative days lacks predictive value to singularly rule out AL. Early and safe discharge in patients undergoing rectal surgery for adenocarcinoma cannot be guaranteed based on this parameter. High negative predictive values are mainly caused by the relatively low prevalence of AL.


Behavioural and electrophysiological effects related to semantic violations during braille reading.
This study investigated the potential to detect event related potentials (ERPs) occurring in response to a specific task in braille reading. This would expand current methodologies for studying the cognitive processes underlying braille reading. An N400 effect paradigm was utilised, whereby proficient blind braille readers read congruent- and incongruent-ending braille sentences. Kinematic and electroencephalography (EEG) data were obtained simultaneously and synchronised. The ERPs differed between the incongruent and congruent sentences in a manner consistent with the N400 effect found with a previous sighted reading paradigm, demonstrating that ERPs can be obtained during braille reading. The frequency of finger reversals and the degree of intermittency in the finger velocity were significantly higher when reading incongruent versus congruent sentence endings. Both reversals and the potential N400 effect may reflect processes involved in semantic unification. These findings have significant implications for the modelling of braille reading. The refinement of the technique will enable other ERPs to be identified and related to behavioural responses, to further our understanding of the braille reading process.


Prevalence of Anisakis larvae in cultured mackerel Scomber japonicas in Japan and the relationship between the intensity of Anisakis infection in cultured mackerel and fish fatness.
Incidences of food poisoning caused by Anisakis have increased in Japan, and a significant number of anisakiasis cases in Tokyo attributed to the consumption of mackerel (Scomber japonicus) have been reported. There are two types of cultured mackerel in Japan: those cultured fully from controlled parent fish eggs and those cultured from wild juveniles collected from the sea. In this study, we aimed to investigate the prevalence of Anisakis larvae in cultured mackerel (184 fish) in 15 products and identified the species using molecular analysis to evaluate the risk of food poisoning. In total, 1567 Anisakis larvae were detected in 70 of 130 mackerel in 10 products; however, Anisakis larvae were not detected in 54 mackerel using artificially reared juveniles in 5 products. Moreover, 277 larvae were detected in fish muscle, and 98.6 % (273/277 larvae) were molecularly identified as Anisakis simplex sensu stricto (A. simplex). Conversely, 1043 Anisakis pegreffii larvae were identified genetically and/or morphologically but only 2 larvae were identified in the muscle. There was no significant relationship between the host coefficient of fatness and the infection intensity of Anisakis larvae in individual fish (Spearman's rank correlation coefficient test, P > 0.05). Based on the results of the analysis of the cytochrome c oxidase subunit2 (cox2) gene of A. simplex and A. pegreffii detected in this study, we attempted to estimate the catch area of the juveniles (Pacific stock and Tsushima Warm Current stock). The clusters on the phylogenetic tree of the cox2 gene of A. pegreffii from the mackerel presumed to be the two above mentioned geographic distributions were not separated and these geographic origins could not be estimated. This study revealed that mackerel cultured using wild juveniles are likely to be contaminated with Anisakis larvae, which can be detected not only in the visceral organs, but also in the muscle. Anisakis infection in cultured mackerel did not influence fish growth and evaluating the intensity of Anisakis based on the fatness level of the mackerel was complicated. To prevent anisakiasis caused by the consumption of mackerel cultured using wild juveniles, it is important to steadily control Anisakis through heating and freezing.


Brain response to empathy-eliciting scenarios involving pain in incarcerated individuals with psychopathy.
A marked lack of empathy is a hallmark characteristic of individuals with psychopathy. However, neural processes associated with empathic processing have not yet been directly examined in psychopathy, especially in response to the perception of other people in pain and distress. To identify potential differences in patterns of neural activity in incarcerated individuals with psychopathy and incarcerated persons serving as controls during the perception of empathy-eliciting stimuli depicting other people experiencing pain. In a case-control study, brain activation patterns elicited by dynamic stimuli depicting individuals being harmed and facial expressions of pain were compared between incarcerated individuals with psychopathy and incarcerated controls. Participants were scanned on the grounds of a correctional facility using the Mind Research Network's mobile 1.5-T magnetic resonance imaging system. Eighty incarcerated men were classified according to scores on the Hare Psychopathy Checklist-Revised (PCL-R) as high (27 men; PCL-R, ≥30), intermediate (28 men; PCL-R, 21-29), or low (25 men; PCL-R, ≤20) levels of psychopathy. Neurohemodynamic response to empathy-eliciting dynamic scenarios revealed by functional magnetic resonance imaging. Participants in the psychopathy group exhibited significantly less activation in the ventromedial prefrontal cortex, lateral orbitofrontal cortex, and periaqueductal gray relative to controls but showed greater activation in the insula, which was positively correlated with scores on both PCL-R factors 1 and 2. In response to pain and distress cues expressed by others, individuals with psychopathy exhibit deficits in the ventromedial prefrontal cortex and orbitofrontal cortex regardless of stimulus type and display selective impairment in processing facial cues of distress in regions associated with cognitive mentalizing. A better understanding of the neural responses to empathy-eliciting stimuli in psychopathy is necessary to inform intervention programs.


Stereotyped behavior in the ontogeny of rats.
The ontogenetic development of stereotyped behavior induced by activation of dopamine D1 and D2 receptors with apomorphine was studied in rat pups (1st month of life) and adult rats (2nd-12th months of life). Stereotyped sniffing and licking movements developed not simultaneously under the influence of apomorphine. Apomorphine-induced sniffing hyperactivity was observed in newborn animals, but disappeared after eye opening (day 18 of life). Stereotyped licking movements (long-term intense licking of the wall of the actograph) induced by activation of dopamine D2 receptors with apomorphine were revealed in rat pups on the 4th week of life. The duration of these movements in rats was maximum by the 9th month of life. The dynamics of stereotyped behavior probably reflects the non-simultaneous formation and development of dopamine D1 and D2 receptors in the ventrolateral striatum during the ontogeny of rats.


Aquaporin 4 antibodies in the cerebrospinal fluid are helpful in diagnosing Chinese patients with neuromyelitis optica.
It was the aim of this study to compare the diagnostic efficiency of anti-aquaporin 4 (AQP4) antibody detection between serum and cerebrospinal fluid (CSF) samples in Chinese patients with central nervous system demyelinating diseases. Anti-AQP4 antibodies were detected by a cell-based assay. We calculated the sensitivity, specificity and coherence in 118 patients with neuromyelitis optica (NMO, n = 39), multiple sclerosis (n = 34), longitudinally extensive transverse myelitis (LETM, n = 22), optic neuritis (ON, n = 6), opticospinal multiple sclerosis (n = 8) and acute partial transverse myelitis (n = 9). Forty-four serum samples (33.8%) were positive for anti-AQP4 antibodies. Anti-AQP4 antibody seropositivity was 76.9, 59.1 and 16.7% in patients with NMO, LETM and ON, respectively. Sixty-five CSF samples (50%) were positive for anti-AQP4 antibodies. Anti-AQP4 antibody positivity was 87.1, 81.8, 83.3, 62.5 and 11.8% in patients with NMO, LETM, ON, opticospinal multiple sclerosis and multiple sclerosis, respectively. The κ value of the coherence test was 0.585 (p < 0.0001) between the two types of samples. The antibody positivity rate was significantly different between the two body fluids (p = 0.0008, McNemar test). The sensitivity and specificity were 74.3 and 100% in serum, 85.7 and 88.2% in CSF, and 94.3 and 88.2% for serum and CSF combined, respectively. The sensitivity of anti-AQP4 antibodies in the CSF was higher than that in the serum, and their combined use is helpful in diagnosing Chinese patients with NMO.


The impact of axillary lymphadenopathy on further treatment in breast cancer? A model for clinical staging.
Clinical assessment is an important part of the breast cancer patients' work-up, but it has low sensitivity and specificity. In a retrospective study, histological slides of axillary clearance specimens were used to model palpability of the axillary lymph nodes. Obvious nodes (enlarged and involving considerable amount of lymphatic and/or metastatic tissue) and nodes equal to or larger than 1 cm or 1.5 cm were counted and the slides were subsequently reviewed. The false positive and negative rates expected on the basis of the model ranged from 24 to 72 % and from 10 to 38 %, respectively. This model (also valid for intraoperative assessment of nodal status by palpation) documents the lack of specificity of clinical staging of the axilla. These results question the practice of excluding patients with palpable axillary lymph node enlargement from less radical staging procedures such as axillary sampling or sentinel node biopsy.


Antepartum mastitis: a case report.
Acute mastitis commonly occurs in the postpartum period. It has been reported only rarely in the antepartum period. A 14-year-old patient presented at 29 weeks gestation with her symptoms and examination consistent with bilateral mastitis that had worsened over 2 months. She had evidence of systemic infection. She was treated with parenteral antibiotics and local skin care. She gradually improved and delivered a healthy infant at term. The management of antepartum mastitis can be derived from experience with puerperal mastitis. It must include early recognition, a search for predisposing factors and causative organisms, and aggressive treatment. Such an approach can lead to successful pregnancy outcome with minimal fetal or maternal morbidity.


Specific association of two homologous DNA-binding proteins to the native 30-S ribosomal subunits of Escherichia coli.
The native 30-S ribosomal subunits from Escherichia coli are shown to be associated with two proteins which are different from the known ribosome-associated and ribosomal proteins. Neither protein is foune on native 50-S subunits or on intact ribosomes in the cell extract. The purified proteins re-bind in vitro to free 30-S subunits, but do not bind to either free 50-S subunits or intact ribosomes. The proteins, denoted NS1 and NS2, have been purified and characterized. Both proteins showed the same molecular weight of 9500 by sodium dodecyl sulfate gel electrophoresis but 34 000 by gel filtration. Upon treatment with cross-linking reagents the purified proteins gave higher molecular weight species up to the tetrameric ones showing that they exist in solution as tetramers. The amino acid compositions, tryptic fingerprint patterns and N-terminal sequences of the two proteins have been determined. These data show that NS1 and NS2 possess distinct primary structures but with extensive sequence homology. Antibodies raised against the purified proteins cross-reacted in double immuno-diffusion tests confirming further the homology. Because of the similarity in properties a sample of the DNA-binding protein HD (Berthold, V. and Geider, K. (1976) Eur. J. Biochem. 71, 443--449) was compared to NS1 and NS2. In terms of several criteria, the protein HD is found to be a mixture of two proteins, namely NS1 and NS2. The present report is the first instance of an association of DNA-binding proteins to the ribosome.


An ultrasensitive sensing platform for microRNA-155 based on H2O2 quenched hydroxide-dependent ECL emission of PFO Pdots.
A strong hydroxide (OH-)-dependent ECL emission of carboxyl functionalized-poly (9,9-di-n-octylfluorenyl-2,7-diyl) polymer dots (PFO Pdots) was observed at +1.25 V, which is significantly stronger than the emission at +1.95 V reported in previous work. Moreover, hydrogen peroxide (H2O2) can efficiently quench OH--dependent ECL emission of PFO Pdots. Based on this discovery, a signal "off-on" ECL biosensing platform for microRNA-155 (miRNA-155) was developed. Firstly, PFO Pdots were modified onto the electrode to capture DNA duplex track-locker. In the presence of H2O2 in the test solution, the ECL signal of PFO Pdots was quenched to obtain a signal-off state. Subsequently, the DNA walker produced through the target miRNA-155-triggered catalytic hairpin assembly (CHA) walked along the DNA duplex track-locker to output amounts of G-rich short chain, forming a hemin/G-quadruplex. With the consumption of H2O2 by hemin/G-quadruplex, the ECL signal would be restored to a signal-on state, thus achieving an ultrasensitive detection of miRNA-155. The detection limit was low as 12.2 aM. Furthermore, our proposed biosensor demonstrated a tremendous selectivity and admirable stability, and exhibited a satisfactory performance for determinating intracellular miRNA-155. The integration of excellent ECL performance of PFO Pdots without any exogenous species or dissolved O2 as co-reactant and a highly efficient quenching effect of H2O2 on such an ECL emission will provide an attractive ECL platform for bioanalysis and clinical diagnosis.


Nitrification performance evaluation of activated sludge under high potassium ion stress during high-ammonia nitrogen organic wastewater treatment.
The recycling reverse osmosis (RO) membrane concentrate of some high-ammonia nitrogen (NH4+-N) organic wastewater to the biological unit could cause potassium ion (K+) accumulation, thereby affecting the removal of NH4+-N by activated sludge. Thus, the effects of high K+ stress on activated sludge nitrification performance was studied. The results showed that the high K+ stress promoted the floc sludge to produce more extracellular polymers (EPS), which accelerated the sludge sedimentation and enriched the biomass in sequential batch reactors (SBRs). The ammonia oxidation process and nitrite (NO2--N) oxidation process were further analyzed in the nitrification process. High K+ stress enriched ammonia oxidizing bacteria (AOB), which ensured the efficient ammonia oxidation process in SBRs, and ensured the removal rate of NH4+-N was maintained above 93%. However, high K+ stress (15g/L KCl) inhibited the activity of NO2--N oxidizing bacteria (NOB) and reduced the abundance of NOB, thus leading to the accumulation of NO2--N, and finally worsened the nitrification performance of activated sludge. In short, the performance of activated sludge will not be inhibited when the K+ in the wastewater does not exceed 5.23 g/L. The results could provide a reference for the optimization of the biological performance in treating high-NH4+-N organic wastewater with activated sludge coupled RO membrane treatment process.


The sustained psychological impact of coronavirus disease 2019 pandemic on hospital workers 2 years after the outbreak: a repeated cross-sectional study in Kobe.
Healthcare workers who are exposed to coronavirus disease 2019 are psychologically distressed. This study aimed to evaluate the mental health outcomes of hospital workers 2 years after the outbreak of coronavirus disease 2019 and to identify changes in the stress of hospital workers and predicted risk factors. This survey was conducted 2 years after the initial evaluation performed under the first emergency declaration of the coronavirus disease 2019 pandemic among hospital workers at the same hospital in an ordinance-designated city in Japan from June to July 2022. Sociodemographic data, 19 stress-related question responses, the Impact of Event Scale-Revised, and the Maslach burnout inventory-general survey were collected. Multiple regression models were used to identify factors associated with each of the mental health outcomes 2 years after the coronavirus disease 2019 outbreak. We received 719 valid responses. Between 2020 and 2022, hospital workers' anxiety about infection decreased, whereas their exhaustion and workload increased. Multiple regression analysis revealed that 2 years after the coronavirus disease 2019 outbreak, nurses and young people were at a higher risk of experiencing stress and burnout due to emotional exhaustion, respectively. This is the first study to examine the long-term stress of hospital workers measured in Japan. Exhaustion and workload were worsened 2 years into the pandemic. Therefore, health and medical institutions should continuously monitor the physical and psychological health of staff members.


Angiogenesis and vascular remodeling in chronic airway diseases.
Asthma and chronic obstructive pulmonary disease remain a global health problem, with increasing morbidity and mortality. Despite differences in the causal agents, both diseases exhibit various degrees of inflammatory changes, structural alterations of the airways leading to airflow limitation. The existence of transient disease phenotypes which overlap both diseases and which progressively decline the lung function has complicated the search for an effective therapy. Important characteristics of chronic airway diseases include airway and vascular remodeling, of which the molecular mechanisms are complex and poorly understood. Recently, we and others have shown that airway smooth muscle (ASM) cells are not only structural and contractile components of airways, rather they bear capabilities of producing large number of pro-inflammatory and mitogenic factors. Increase in size and number of blood vessels both inside and outside the smooth muscle layer as well as hyperemia of bronchial vasculature are contributing factors in airway wall remodeling in patients with chronic airway diseases, proposing for the ongoing mechanisms like angiogenesis and vascular dilatation. We believe that vascular changes directly add to the airway narrowing and hyper-responsiveness by exudation and transudation of proinflammatory mediators, cytokines and growth factors; facilitating trafficking of inflammatory cells; causing oedema of the airway wall and promoting ASM accumulation. One of the key regulators of angiogenesis, vascular endothelial growth factor in concerted action with other endothelial mitogens play pivotal role in regulating bronchial angiogenesis. In this review article we address recent advances in pulmonary angiogenesis and remodelling that contribute in the pathogenesis of chronic airway diseases.


Lodoxamide tromethamine treatment for superior limbic keratoconjunctivitis.
We studied the efficacy of topically applied lodoxamide tromethamine 0.1% in the treatment of superior limbic keratoconjunctivitis. Three patients with clinical findings of bilateral superior limbic keratoconjunctivitis. were treated with topical lodoxamide tromethamine four times daily in both eyes. While the patients were taking lodoxamide tromethamine, symptoms and objective findings resolved. Topically applied lodoxamide tromethamine 0.1% is useful in the treatment of superior limbic keratoconjunctivitis. There may be a role for mast cell stabilizers in the treatment of this disorder.


Strongyloides stercoralis hyperinfection in a post-renal transplant patient.
Strongyloides stercoralis is an intestinal nematode that is able to infect the host tissue and persist asymptomatic for many years through autoinfection. It causes life-threatening hyperinfection in immunocompromised hosts. This report describes a rare case of strongyloidiasis in a 40-year-old male following renal transplant, which was diagnosed by colonoscopic biopsy. The literature on the subject is also reviewed.


Reduced serum dehydroepiandrosterone levels in diabetic patients with hyperinsulinaemia.
To elucidate the interaction between insulin and dehydroepi-androsterone (DHEA) concentrations, we evaluated serum DHEA and DHEA-sulphate (DHEA-S) levels in diabetic patients with hyperinsulinaemia. Twenty-four subjects with non-insulin dependent diabetes mellitus, 12 hyperinsulinaemic subjects (fasting serum insulin concentrations > or = 10 mU/ml (71.8 pmol/l)) and 12 non-hyperinsulinaemic subjects, and 10 normal control subjects were studied. Serum DHEA, DHEA-S, cortisol and ACTH levels were investigated in these subjects. Moreover, their serum DHEA levels were compared during hyperinsulinaemic-euglycaemic clamp and after ACTH stimulation. Serum insulin, cortisol, ACTH, DHEA and DHEA-S concentrations were evaluated by RIA. Serum glucose was determined by the glucose oxidase method. Diabetic patients with hyperinsulinaemia showed significantly lower levels of serum DHEA and DHEA-S than controls. After ACTH stimulation, these patients also showed significantly lower DHEA levels. During the hyperinsulinaemic-euglycaemic clamp, serum DHEA concentrations of diabetic patients with hyperinsulinaemia remained low and did not decline further, although those of control subjects and non-hyperinsulinaemic diabetic patients showed a significant decline of serum DHEA levels. Even after ACTH stimulation during the clamp, serum DHEA in hyperinsulinaemic patients was still significantly lower than in controls. In diabetic patients with hyperinsulinaemia, baseline DHEA levels are chronically and maximally suppressed compared to control subjects and non-hyperinsulinaemic diabetic patients, and thus not decreased further by exogenous insulin infusion during hyperinsulinaemic-euglycaemic clamp.


Receptor sites for Ca2+ channel antagonists.
Ca2+ channel antagonist drugs inhibit voltage-gated Ca2+ channels in many different cell types. Inhibition of Ca2+ channels in smooth muscle and cardiac muscle cells by these drugs is valuable in the therapy of a wide range of cardiovascular disorders including hypertension, atrial arrhythmia and angina pectoris. Additional uses under evaluation are protection against ischemic damage during myocardial infarction and stroke and in a wide range of other conditions. Further understanding of the sites and mechanisms of action of Ca2+ channel antagonists, as described in this review by Bill Catterall and Jörg Striessnig, will provide new insight into the design of novel therapeutic agents acting on Ca2+ channels and provide further understanding of Ca2+ channel structure and function.


Stigma, gender dysphoria, and nonsuicidal self-injury in a community sample of transgender individuals.
We investigated rates of nonsuicidal self-injury (NSSI) and correlates of past-year NSSI among transgender people to better understand factors contributing to this health disparity. A community-based sample of 332 transgender people participated in quantitative in-person interviews. The mean age of participants was 34.56 years (SD = 13.78, range = 16-87). The sample was evenly divided between transfeminine spectrum (50.3%) and transmasculine spectrum identities (49.7%) and was diverse in race/ethnicity. We evaluated associations between sociodemographic characteristics, stigma, hypothesized resilience factors, and identity variables with past-year NSSI. 53.3% of participants reported ever having self-injured in their lifetime. Past-year NSSI was reported by 22.3% of the sample and did not significantly differ based on gender identity. In logistic regression models, past-year NSSI was associated with younger age and felt stigma (perceived or anticipated rejection), but not enacted stigma (actual experiences of discrimination), and with gender dysphoria. Efforts to address the high rates of NSSI among transgender people should aim to reduce felt stigma and gender dysphoria, and promote transgender congruence. Future research using a developmental approach to assess variations in NSSI across the life course and in relation to transgender identity development may illuminate additional processes that affect NSSI in this population.


Electrophysiological responses of receptor neurons in mosquito maxillary palp sensilla to carbon dioxide.
Sensilla basiconica on the maxillary palps of female Aedes aegypti contain a receptor neuron which produces a phasic-tonic pattern of action potential response to low concentrations (150-300 ppm) of carbon dioxide (CO2), a stimulus known to be involved with host seeking behavior. These receptor neurons respond reliably to small increments in CO2 concentration (e.g., 50 ppm). We were particularly interested in evaluating the possibility that the sensitivity to step increases in CO2 concentration could be modulated by alterations in the background levels of CO2, over a range which might be encountered during host-seeking behavior. We report here that the response (impulses/s) to a single pulse of a given concentration of CO2 appears to be independent of the background level of CO2, unless that level is equal to or greater than the concentration of the stimulus pulse. Females of other mosquito species, including: Anopheles stephensi, Culex quinquefasciatus, Culiseta melanura, and Aedes taeniorhynchus, also possess sensilla with receptor neurons that respond with comparable sensitivity to CO2 stimulation. However, there is much interspecific variation in both the external morphology of the maxillary palp and the distribution of sensilla along the palp. Male Ae. aegypti have morphologically similar sensilla which also contain a receptor neuron that responds to CO2.


Application of System Biology to Explore the Association of Neprilysin, Angiotensin-Converting Enzyme 2 (ACE2), and Carbonic Anhydrase (CA) in Pathogenesis of SARS-CoV-2.
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears with common symptoms including fever, dry cough, and fatigue, as well as some less common sysmptoms such as loss of taste and smell, diarrhea, skin rashes and discoloration of fingers. COVID-19 patients may also suffer from serious symptoms including shortness of breathing, chest pressure and pain, as well as loss of daily routine habits, pointing out to a sever reduction in the quality of life. COVID-19 has afftected almost all countries, however, the United States contains the highest number of infection (> 1,595,000 cases) and deaths cases (> 95,000 deaths) in the world until May 21, 2020. Finding an influential treatment strategy against COVID-19 can be facilitated through better understanding of the virus pathogenesis and consequently interrupting the biochemical pathways that the virus may play role in human body as the current reservoir of the virus. In this study, we combined system biology and bioinformatic approaches to define the role of coexpression of angiotensin-converting enzyme 2 (ACE2), neprilysin or membrane metallo-endopeptidase (MME), and carbonic anhydrases (CAs) and their association in the pathogenesis of SARS-CoV-2. The results revealed that ACE2 as the cellular attachment site of SARS-CoV-2, neprilysin, and CAs have a great contribution together in the renin angiotensin system (RAS) and consequently in pathogenesis of SARS-CoV-2 in the vital organs such as respiratory, renal, and blood circulation systems. Any disorder in neprilysin, ACE2, and CAs can lead to increase of CO2 concentration in blood and respiratory acidosis, induction of pulmonary edema and heart and renal failures. Due to the presence of ACE2-Neprilysin-CA complex in most of vital organs and as a receptor of COVID-19, it is expected that most organs are affected by SARS-CoV-2 such as inflammation and fibrosis of lungs, which may conversely affect their vital functions, temporary or permanently, sometimes leading to death. Therefore, ACE2-Neprilysin-CA complex could be the key factor of pathogenesis of SARS-CoV-2 and may provide us useful information to find better provocative and therapeutic strategies against COVID-19.


Assessment of physical performance using the 6-minute walk test in children receiving treatment for cancer.
The study of physical performance in children with cancer is emerging as an important variable in symptom research. Studies have shown that children with cancer experience deficits in physical performance during treatment that may be present years after therapy. The aim of this study was to determine if distance on the 6-minute walk test (6MWT) changed in children during the first 3 cycles of cancer treatment and to compare the distances walked with healthy norms. This is a secondary data analysis of 19 boys and 10 girls, aged 6 to 17 years, who were newly diagnosed with cancer and were part of a larger study that measured changes in fatigue and physical performance during the first 3 cycles of chemotherapy. Participants performed the 6MWT between days 15 and 29 of the first and third cycles of chemotherapy. Pediatric cancer patients did not have a significant change in the distance walked at cycle 3 of chemotherapy compared with cycle 1. When compared with 2 different normative data sets for healthy children, most children with cancer performed significantly below their peers. Children had poor strength and endurance after 3 cycles of chemotherapy even when their disease was responding to treatment. Interventions are needed to promote rehabilitation and maintenance of physical performance, as both are important to quality of life and ongoing child development. Children receiving cancer treatment who are ambulatory may appear to be functioning normally but are in fact severely deconditioned compared with their healthy peers.


Attitudes of Students at a US Medical School Toward Mental Illness and Its Causes.
Stigma among health care providers toward people with mental illness is a worldwide problem. This study at a large US university examined medical student attitudes toward mental illness and its causes, and whether student attitudes change as they progress in their education. An electronic questionnaire focusing on attitudes toward people with mental illness, causes of mental illness, and treatment efficacy was used to survey medical students at all levels of training. Exploratory factor analysis was used to establish attitudinal factors, and analysis of variance was used to identify differences in student attitudes among these factors. Independent-samples t tests were used to assess attitudes toward efficacy of treatments for six common psychiatric and medical conditions. The study response rate was 42.6 % (n = 289). Exploratory factor analysis identified three factors reflecting social acceptance of mental illness, belief in supernatural causes, and belief in biopsychosocial causes. Stages of student education did not differ across these factors. Students who had completed the psychiatry clerkship were more likely to believe that anxiety disorders and diabetes could be treated effectively. Students reporting personal experiences with mental illness showed significantly more social acceptance, and people born outside the USA were more likely to endorse supernatural causes of mental illness. Sociocultural influences and personal experience with mental illness have a greater effect than medical education on attitudes toward people with mental illness. Psychiatric education appears to have a small but significant effect on student attitudes regarding treatment efficacy.


Evaluation of celiac artery and common hepatic artery variations by CT-angiography and new classification model.
Knowledge of anatomical variations is important in all interventional procedures. This study aims to evaluate the variations and prevalence of celiac trunk (CeT) and its branches. The computerized tomography-angiography (CT-A) findings of 941 adult patients were evaluated retrospectively. Variations of the CeT and common hepatic artery (CHA) were evaluated according to the number of branches and their origin. Findings were compared with classical classification methods. A new classification model has been defined. Normal (complete) trifurcation was detected in 856 (90.9%) of them, where left gastric artery (LGA), splenic artery (SpA) and CHA branches were derived from the CeT. Among 856 complete trifurcation cases, 773 (90.3%) had non-classical trifurcation patterns. The rate of classic trifurcation was 8.8%, while non-classic trifurcation was 82.1% in all cases. In one case (0.1%), LGA and left hepatic artery together and right hepatic artery and SpA together appeared as a double bifurcation. Complete celiacomesenteric trunk was observed only in 4 (0.42%) cases. In seven cases (0.7%), LGA, SpA and CHA were coming out of abdominal aorta (AAo) independently. CHA normal anatomy (Michels Type I) was detected in 618 (65.5%) patients. We found that 49 (5.2%) of our cases were ambiguous according to the Michels Classification. We have described five different variations of hepatic arteries directly arising from the AAo. Preoperative recognition of anatomical variations of CeT, superior mesenteric artery and CHA is of primary importance in both surgical and radiological procedures. With careful evaluation of CT-angiographies, it is possible to detect rare variations.


Reference ranges for sonographic dimensions of the liver and spleen in preterm infants.
Preterm infants usually have multiple comorbidities that affect spleen and liver. Ultrasonographic measurement of organ sizes is an important and reliable parameter in evaluation of spleen and liver pathology in preterm newborns. The purpose of this study was to determine reference values of ultrasonographic measurements of the liver and spleen in preterm newborns. We prospectively performed sonography on 498 preterm newborns in the first week of life. We measured spleen and liver dimensions and statistically analyzed relationships between the dimensions and gender, gestational age (based on mother's last menstrual period), height and weight. Reference ranges of dimensions were defined. Longitudinal and anteroposterior dimensions of the liver and spleen were statistically significantly different between the boys and girls (P < 0.05) and showed high correlation with the gestational age, weight and height. Weight was the parameter best correlated with the dimensions. Nomograms from these data are useful for sonographic evaluation of the liver and spleen in preterm newborns.


Diagnostic accuracy of cardiovascular magnetic resonance for patients with suspected cardiac amyloidosis: a systematic review and meta-analysis.
This study is a systematic review and meta-analysis of the diagnostic value of cardiovascular magnetic resonance (CMR) in cardiac amyloidosis (CA). A wide variety of electronic databases were searched for studies of CMR that reported the diagnostic accuracy in patients with suspected CA. Research manuscripts were subjected to further systematic review and meta-analysis. Methodological evaluation was performed under the guidance of the Quality Assessment of Diagnostic Accuracy Studies -2 (QUADAS-2). Heterogeneity was assessed, and a random-effects model was used to assess the diagnostic effects of CMR on pooled sensitivity, pooled specificity, and summary receiver operating characteristics (SROC). Seven studies that reported the performance of CMR for CA were included in the present systematic review, among which five studies (257 patients) that evaluated the diagnostic accuracy of late gadolinium enhancement (LGE) CMR were analyzed in the present meta-analysis. Heterogeneity was observed only in specificity. A summary sensitivity and specificity of 85 % (95 % CI: 77-91 %) and 92 % (95 % CI: 83-97 %) indicated a high diagnostic accuracy of LGE for CA. The AUC of SROC curve was 0.9530, suggesting that LGE is an effective way of diagnosing patients with possible cardiac involvement in amyloidosis. LGE-CMR seems to have a relatively high diagnostic accuracy for amyloidosis patients with possible cardiac involvement. Combined CMR techniques may provide important information for the selection of suitable therapy.


Uca (Petruca), a new subgenus for the rock fiddler crab Uca panamensis (Stimpson, 1859) from Central America, with comments on some species of the American broad-fronted subgenera.
Among the fiddler crabs from the Americas, Uca panamensis (Stimpson, 1859) (Crustacea: Decapoda: Ocypodidae) is unusual in its behavior and ecology, living in stony habitats rather than sandy or muddy substrates. This species also has several unusual morphological characters of the carapace and major and minor chelae, and had been placed in either the subgenera Minuca Bott, 1954, or Leptuca Bott, 1973. The armature at the inner corner of the orbital floor, as well as the morphology of the urocardiac ossicles of the gastric mill of U. panamensis, are, however, plesiomorphic characters, and are closer to the condition in species belonging the subgenera Uca and Afruca. Phylogenetic relationships, based on mitochondrial 16S rDNA and cytochrome oxidase subunit I, and nuclear 28S rDNA, supported by its unusual morphological features indicate that this species belongs to its own subgenus. A new subgenus Uca (Petruca) subgen. nov. is herein established for U. panamensis. In addition, the status of Uca thayeri Rathbun, 1900, U. umbratila Crane, 1941, U. virens Salmon & Atsaides, 1968, and U. longisignalis Salmon & Atsaides, 1968, are revised and discussed based on a reappraisal of their phylogenetic relationships.


Melatonin for prevention of postoperative delirium after lower limb fracture surgery in elderly patients (DELIRLESS): study protocol for a multicentre randomised controlled trial.
Postoperative delirium (POD) is one of the most frequent complication after surgery in elderly patients, and is associated with increased morbidity and mortality, prolonged length of stay, cognitive and functional decline leading to loss of autonomy, and important additional healthcare costs. Perioperative inflammatory stress is a key element in POD genesis. Melatonin exhibits antioxidative and immune-modulatory proprieties that are promising concerning delirium prevention, but in perioperative context literature are scarce and conflicting. We hypothesise that perioperative melatonin can reduce the incidence of POD. The DELIRLESS trial is a prospective, national multicentric, phase III, superiority, comparative randomised (1:1) double-blind clinical trial. Among patients aged 70 or older, hospitalised and scheduled for surgery of a severe fracture of a lower limb, 718 will be randomly allocated to receive either melatonin 4 mg per os or placebo, every night from anaesthesiologist preoperative consultation and up to 5 days after surgery. The primary outcome is POD incidence measured by either the French validated translation of the Confusion Assessment Method (CAM) score for patients hospitalised in surgery, or CAM-ICU score for patients hospitalised in ICU (Intensive Care Unit). Daily delirium assessment will take place during 10 days after surgery, or until the end of hospital stay if it is shorter. POD cumulative incidence function will be compared at day 10 between the two randomised arms in a competing risks framework, using the Fine and Grey model with death as a competing risk of delirium. The DELIRLESS trial has been approved by an independent ethics committee the Comité de Protection des Personnes (CPP) Sud-Est (ref CPP2020-18-99 2019-003210-14) for all study centres. Participant recruitment begins in December 2020. Results will be published in international peer-reviewed medical journals. NCT04335968, first posted 7 April 2020. N°3-0, 3 May 2021.


Meningeal lymphatics clear erythrocytes that arise from subarachnoid hemorrhage.
Extravasated erythrocytes in cerebrospinal fluid (CSF) critically contribute to the pathogenesis of subarachnoid hemorrhage (SAH). Meningeal lymphatics have been reported to drain macromolecules and immune cells from CSF into cervical lymph nodes (CLNs). However, whether meningeal lymphatics are involved in clearing extravasated erythrocytes in CSF after SAH remains unclear. Here we show that a markedly higher number of erythrocytes are accumulated in the lymphatics of CLNs and meningeal lymphatics after SAH. When the meningeal lymphatics are depleted in a mouse model of SAH, the degree of erythrocyte aggregation in CLNs is significantly lower, while the associated neuroinflammation and the neurologic deficits are dramatically exacerbated. In addition, during SAH lymph flow is increased but without significant lymphangiogenesis and lymphangiectasia. Taken together, this work demonstrates that the meningeal lymphatics drain extravasated erythrocytes from CSF into CLNs after SAH, while suggesting that modulating this draining may offer therapeutic approaches to alleviate SAH severity.


Local lymph node assay - validation, conduct and use in practice.
The validation of alternative methods is a relatively new activity in toxicology. The local lymph node assay (LLNA), a novel method for the identification of chemicals that have the potential to cause skin sensitization, was the first test to pass through the formal regulatory validation process established in the USA under the auspices of ICCVAM, the Interagency Coordinating Committee on the Validation of Alternative Methods. ICCVAM approved the LLNA as an alternative to guinea pig tests for the identification of skin sensitisation hazards. In this report, we explore the nine recommendations made by ICCVAM and discuss their interpretation in relation to the new OECD Guideline 429, which describes the LLNA. In particular, the value and limitations of the use of statistical evaluation of data and of the inclusion of routine positive controls is examined. It is concluded that the OECD Guideline as currently written embodies the necessary flexibility to permit conduct of the LLNA in a manner necessary to meet the varying needs of regulatory agencies and toxicologists around the world.


Excavation, identification and structure-activity relationship of heat-stable umami peptides in the processing of Wuding chicken.
Umami peptides from different stages of Wuding chicken processing were discovered, isolated, and purified using ultrafiltration membrane, gel filtration chromatography, and reversed-phase high-performance liquid chromatography, and the binding mechanism was explored. Twelve umami peptides were found by nano-scale liquid chromatography-tandem mass spectrometry, three of which (HLEEEIK, LDDALR, and ELY) existed throughout the processing step. The umami score and the frequency of active fragments of umami were highest for LEEEL, followed by EEF. The main active sites between umami peptide and receptor T1R1/T1R3 were Tyr262, Glu325, and Glu292, and hydrophobic interaction and hydrogen bonding were the main forces, and bitter amino acids were also important components of umami peptides. It was found for the first time that heat-stable umami peptides exist in Wuding chickens, which provides a basis for the identification and screening of umami peptides in local chickens, and also helps to study the structure-activity relationship of umami peptides.


[Strategy in preventing of uretero-intestinal anastomosis strictures in patients with low-pressure intestinal neobladder].
Ureteroileal stenoses occur in 1.2-20% patients with neobladders. They constitute a serious clinical complication since, as every obstruction of urine flow from the kidney. Ureteroileal stenoses develop usually within firs 6 to 12 months following the extended urological procedure such as radical cystectomy with the creation of ileal orthotopic neobladder. Ureteroileal stenosis belongs to the most difficult complications after creation of ileal neobladder. The experience of our clinic between 2001 and 2011 covers 3500 cases of patients with bladder cancer. 226 patients underwent cystectomy, 120 were treated with urinary diversion m. Bricker and 106 underwent low pressure ileal neobladder modo Studer. Ureters anastomosed with the intestine Michalowskis way of a flap. The authors performed 344 ureteroileal anastomoses, 212 ureteroileal anastomoses with the ileal neobladder modo Studer and 11 stenoses were detected, in 5 patients one-side, in 3 bilateral. In our practice there was altogether 11 detected stenoses which constitutes 5.18%. Based on our experience, in the course of radical removal of the bladder during the preparation of the least possible damage the blood supply ureter, ureter prior to implantation should be checked for leaks, catheter should be made of soft material. The performance of the left ureter to carry out the right side of the mesentery, be careful not without angulation. In the course of the uretero-intestinal anastomosis should not be stitched in place to destroy the vascular anastomosis of ureter to intestine anastomosis and the same should be done without tension. Protect the integrity of the anastomosis, aseptic oncology. Uretero-intestinal anastomosis performed without anti-reflux protection.


neo-Clerodane diterpenoids from Teucrium oliverianum and structure revision of teucrolin E.
The aerial parts of Teucrium oliverianum yielded two neo-clerodane diterpenoids, teucrolin F and G, together with the known teucrolin E. The previously proposed structure for teucrolin E was revised so that it contains a tetrahydrofuran ring instead of an oxetane ring. This was based on analysis of the NMR spectroscopic data of its diacetate, including its NOE spectra. In addition, the structural assignments of the new diterpenoids were based on 1H and 13C NMR spectroscopic studies, mainly 2D NMR experiments, including homonuclear and heteronuclear correlations.


In vitro activities of N-acetyl cysteine and levofloxacin as a catheter lock therapy against catheter-associated infections.
Since management of catheter-associated infections, which are generally biofilm-based, is attempted in certain patients such as older and frail patients by using a catheter lock solution (CLS), we examined the combination of N-acetyl cysteine (NAC), an antibiofilm agent, and levofloxacin, a broad-spectrum antimicrobial agent, for this purpose. Intravascular catheters were colonized with methicillin-resistant Staphylococcus epidermidis, levofloxacin-sensitive/methicillin-resistant Staph. aureus, levofloxacin-resistant/methicillin-resistant Staph. aureus, vancomycin-resistant Enterococcus, Escherichia coli, Klebsiella pneumoniae or Pseudomonas aeruginosa and treated with a CLS containing normal saline, NAC, levofloxacin or NAC plus levofloxacin (NACLEV) and then cultured to assess their antimicrobial activities. We also examined antibiofilm and antimicrobial activities of each CLS by scanning electron microscopy (SEM) and the mechanical integrity of catheters exposed to CLS. Treatment of colonized catheters with NACLEV-CLS significantly reduced colonization (p < 0.005) against all pathogens. SEM images also indicate reduction in colonization with NACLEV-CLS with considerable reduction in both visible bacteria and the associated biofilm. Mean tensile strength of catheters exposed to CLS was not significantly different compared to controls (p > 0.05). These in vitro results suggest that NACLEV-CLS can significantly reduce all bacterial colonization and potentially help salvage infected catheters without affecting the catheter's mechanical integrity. This study presents a novel CLS with a broad spectrum of antimicrobial activity against catheter-associated infections, particularly in long-term catheters.


Evaluating alternate discrete choice frameworks for modeling ordinal discrete variables.
There is considerable debate on the appropriate discrete choice framework for examining injury severity. Researchers in the safety field have employed ordered and unordered frameworks for examining the various factors influencing injury severity. The objective of the current study is to investigate the performance of the ordered and unordered response frameworks at a fundamental level. Towards this end, we undertake a comparison of the alternative frameworks by estimating ordered and unordered response models using data generated through ordered, unordered data and a combination of ordered and unordered data generation processes. We also examine the influence of aggregate sample shares on the appropriateness of the modeling framework. Rather than be limited by the aggregate sample shares in an empirical dataset, simulation allows us to explore the influence of a broad spectrum of sample shares on the performance of ordered and unordered frameworks. We also extend the data generation process based analysis to under reported data and compare the performance of the ordered and unordered response frameworks. Finally, based on these simulation exercises, we provide a discussion of the merits of the different approaches. The results clearly highlight the emergence of the generalized ordered logit model as a true equivalent ordered response model to the multinomial logit model for ordinal discrete variables.


Rapid diagnosis of smear-negative pulmonary tuberculosis via fibreoptic bronchoscopy: utility of polymerase chain reaction in bronchial aspirates as an adjunct to transbronchial biopsies.
Fibreoptic bronchoscopy was performed on 190 patients with chest radiographic lesions and negative sputum smears for acid-fast bacilli. Aside from obtaining transbronchial biopsies for histological examination, bronchial aspirate specimens were also tested for Mycobacterium tuberculosis complex DNA by a conventional polymerase chain reaction (PCR) technique. Of 177 transbronchial biopsies performed, a diagnosis was found in 64 cases [43 cases of tuberculosis (TB), 17 cases of lung carcinoma and four cases of other infective/inflammatory diseases] giving a diagnostic yield of 36.2%. PCR was positive in 105 of 108 finally diagnosed cases of TB and 22 of 82 non-TB cases. The sensitivity, specificity, positive predictive value and negative predictive value of PCR when applied to bronchial aspirate specimens for diagnosing smear-negative pulmonary TB were 97.2%, 73.2%, 82.7% and 95.2% respectively. Therefore, detection of M. tuberculosis complex DNA in bronchial aspirates by PCR might have an adjunctive place to transbronchial biopsies in the rapid diagnosis of smear-negative pulmonary tuberculosis.


Autopsy, thanatopraxy, cemeteries and crematoria as hotspots of toxic organic contaminants in the funeral industry continuum.
The occurrence and health risks of toxic organic contaminants (TOCs) in the funeral industry are relatively under-studied compared to other industries. An increasing body of literature reports TOCs including emerging contaminants in the funeral industry, but comprehensive reviews of the evidence are still lacking. Hence, evidence was analysed to address the proposition that, the funeral industry constitutes several hotspot reservoirs of a wide spectrum of TOCs posing ecological and human health risks. TOCs detected include embalming products, persistent organic pollutants, synthetic pesticides, pharmaceuticals, personal care products and illicit drugs. Human cadavers, solid wastes, wastewaters and air-borne particulates from autopsy, thanatopraxy care facilities (mortuaries, funeral homes), cemeteries and crematoria are hotspots of TOCs. Ingestion of contaminated water, and aquatic and marine foods constitutes non-occupational human exposure, while occupational exposure occurs via inhalation and dermal intake. Risk factors promoting exposure to TOCs include unhygienic burial practices, poor solid waste and wastewater disposal, and weak and poorly enforced regulations. The generic health risks of TOCs are quite diverse, and include; (1) genotoxicity, endocrine disruption, teratogenicity and neurodevelopmental disorders, (2) development of antimicrobial resistance, (3) info-disruption via biomimicry, and (4) disruption of ecosystem functions and trophic interactions. Barring formaldehyde and inferential evidence, the epidemiological studies linking TOCs in the funeral industry to specific health outcomes are scarce. The reasons for the lack of evidence, and limitations of current health risk assessment protocols are discussed. A comprehensive framework for hazard identification, risk assessment and mitigation (HIRAM) in the funeral industry is proposed. The HIRAM includes regulatory, surveillance and control systems such as prevention and removal of TOCs. Future directions on the ecotoxicology of mixtures, behaviour, and health risks of TOCs are highlighted. The opportunities presented by emerging tools, including isotopic labelling, genomics, big data analytics (e.g., machine learning), and in silico techniques in toxicokinetic modelling are highlighted.


The Role of 68 Ga-FAPI PET/CT in Breast Cancer Response Assessment and Follow-Up.
68 Ga-fibroblast activation protein inhibitor (FAPI), a new PET/CT radiotracer targeting cancer-associated fibroblasts in tumor microenvironment, can detect many types of cancer. We aimed to assess whether it can also be used for response assessment and follow-up. We followed up patients with FAPI-avid invasive lobular breast cancer (ILC) before and after treatment changes and correlated qualitative maximal intensity projection images and quantitative tumor volume with CT results and blood tumor biomarkers. Six consenting ILC breast cancer patients (53 ± 8 years old) underwent a total of 24 scans (baseline for each patient and 2-4 follow-up scans). We found a strong correlation between 68 Ga-FAPI tumor volume and blood biomarkers ( r = 0.7, P < 0.01), but weak correlation between CT and 68 Ga-FAPI maximal intensity projection-based qualitative response assessment. We found a strong correlation between ILC progression and regression (as assessed by blood biomarkers) and 68 Ga-FAPI tumor volume. 68 Ga-FAPI PET/CT could possibly be used for disease response assessment and follow-up.


Performance of Holstein calves receiving equal solids per day from high-solids milk and milk replacer blend once or twice daily combined with dry versus wet fine-particle starter diet.
This study examined the effects of frequency of feeding high-solids milk and milk replacer (MMR) blend combined with dry matter (DM) content of starter feed on the performance of dairy calves. Forty-eight Holstein calves (40.2 ± 3.33 kg of body weight) were randomly assigned to 1 of 4 treatments in a completely randomized design. Based on a combination of 2 MMR feeding frequencies (once versus twice daily) and 2 starter DM levels (91.1 and 50% DM), 4 treatments were designed as (1) once daily + dry starter feed (OD), (2) once daily + wet starter feed (OW), (3) twice daily + dry starter feed (TD), and (4) twice daily + wet starter feed (TW). The amount of milk replacer powder added to whole milk was adjusted at each feeding frequency to ensure that calves received similar solids from the MMR blend via the twice-daily (total solids = 18.6%) or once-daily (total solids = 31.0%) programs. Starter intake in the preweaning period did not differ between treatments (average 0.39 kg of DM/d), but the postweaning starter intake was greater in calves fed the wet starter (OW and TW) than in those fed the dry starter (OD and TD). Calves receiving the high-solids MMR blend twice versus once daily grew faster before weaning, which was reflected by a greater weaning weight in the TD and TW groups (88.9 kg) than in the OD and OW groups (83.2 kg). The daily growth rate after weaning did not differ between treatments and averaged 1.15 kg/d. Gain-to-feed ratio during the preweaning period was greater in calves from TD and TW (mean 0.67) than in calves from the OD or OW groups (mean 0.58). Postweaning gain-to-feed ratio was not different among treatments and averaged 0.38. Days to first diarrhea and duration of diarrhea (4.66 ± 0.38), as well as days that animals were treated with antibiotics, remained unaffected with treatments. Although preweaning body weight gain was lower with once-daily milk feeding, calves were twice as heavy at weaning as at birth in both milk feeding programs regardless of starter moisture content, which may qualify the once-daily milk feeding program as a cost-effective management strategy in commercial calf-rearing operations. Feeding solutions with a high solids content (above 15%) may be associated with an increased risk of abomasal bloat and should be used with caution.


Pehuén (Araucaria araucana) seed residues are a valuable source of natural antioxidants with nutraceutical, chemoprotective and metal corrosion-inhibiting properties.
In the last decade, green chemistry has been attracting great interest in many contexts, including, among others, natural antioxidants. However, only a few works deal with natural residue extracts and biowaste, which could be an efficient, economical and environmentally friendly source for the production of useful compounds. In this study, we look for antioxidant activity in Araucaria araucana seeds, an iconic pine species of the Argentine and Chilean Patagonia commonly known as "pehuén". Piñones are the edible pehuén seeds, and it is estimated that approximately 40 tons of piñones are harvested annually in Argentina and Chile. The chemical composition, antioxidants, metal corrosion-inhibiting properties and biological activity of edible and discarded piñón tissues were determined. Acute toxicity was discarded by in vitro testing and double fluorescent staining. Biological activity was evaluated in vivo by determining redox markers in salivary glands from rats treated with Cyclophosphamide (an oncological drug). All piñón tissues had antioxidants and antioxidant activity, with the coats showing the highest levels (up to 404 µg ascorbic acid equivalent per mg). The coats, in particular, had high gallic acid, catechin, quercetin and tannin contents, and more antioxidant activity, polyphenols and flavonoids than berries from the region. Results by X-ray fluorescence spectrometry showed that Na, Mg, P, S, Cl, K, and Ca were majority elements in the coat, embryo and endosperm. Furthermore, coat extract also showed significant anti-corrosion activity and in vivo protection against oxidative damage. The results indicate that piñón biowaste is a low-cost attractive source of natural antioxidants with potential nutraceutical, medical and metal corrosion protection applications.


Anomalous palmar cutaneous branch of the median nerve in the distal forearm: case report.
Variations exist in the anatomy of the palmar cutaneous branch of the median nerve about the wrist. We report an anatomic variation in the course of the palmar cutaneous branch of the median nerve identified in a 17-year-old girl undergoing surgery for a scaphoid nonunion. Instead of coursing ulnar to the flexor carpi radialis tendon, deep to the antebrachial fascia between the tendons of the flexor carpi radialis and palmaris longus, the palmar cutaneous branch of the median nerve was noted to cross volar to the distal aspect of the flexor carpi radialis to lie on its radial aspect. Knowledge of the anatomic variant described in this report should encourage surgeons to dissect carefully as they expose the flexor carpi radialis during the exposure of the distal radius or scaphoid.


Number and sex ratio of children and impact of parental diabetes in individuals with Type 1 diabetes.
To assess the number and sex ratio of children in individuals with Type 1 diabetes mellitus and the influence of parental diabetes on age at onset of Type 1 diabetes in our cohort. In a cross-sectional study in a German region comprising 350,000 inhabitants, 697 subjects with Type 1 diabetes (364 women, 333 men) underwent a standardized assessment regarding the number and sex of their children and the family history of diabetes. Compared with 1.36 children per woman in the German background population, the total fertility rate in the calendar year of 2010 in our female cohort with Type 1 diabetes (age 18-49 years) was 0.88. Men with Type 1 diabetes had a fertility rate of 0.65. More men (51.1%) than women (35.7%; P < 0.0001) were childless. Twenty per cent of all women aged 41-45 years in the background population were childless compared with 36.2% of all women and 52% of all men in this specific age group from our cohort. The sex ratio of female vs. male offspring of individuals with Type 1 diabetes did not differ significantly from the expected 1:1 ratio. Maternal Type 1 or Type 2 diabetes increased the age at onset of Type 1 diabetes from 22.9 ± 13.7 (no maternal diabetes) to 28.6 ± 16.8 and 30.1 ± 15.1 years (p < 0.0001), respectively. Compared with the German reference population, individuals with Type 1 diabetes had significantly fewer children and were more often childless. The sex ratio female vs. male offspring of women and men with Type 1 diabetes was unaffected. Maternal history of Type 1 and Type 2 diabetes was associated with a significant later onset of Type 1 diabetes.


Intraoperative changes in blood pressure associated with cerebral desaturation in infants.
Intraoperative hypotension has been linked to poor postoperative neurological outcomes. However, the definition of hypotension remains controversial in children. We sought to determine arterial blood pressure threshold values associated with cerebral desaturation in infants. After ethics committee approval, infants younger than 3 months were included in this prospective observational study. Cerebral saturation was assessed using near-infrared spectroscopy. The primary goal of the study was to determine percentage reductions in intraoperative systolic blood pressure (SBP) and mean blood pressure (MBP) associated with decreases in cerebral blood oxygen saturation of >20%, when compared to baseline. Analyses were performed using a bootstrap receiving operator characteristic (ROC) curves with determination of the gray zone. Sixty patients were recruited and 960 measurement points were recorded. Fifty-nine data points (6.1%) recorded cerebral desaturation of >20% when compared to baseline. The areas under the ROC curves were 0.79 (0.74-0.84) and 0.67 (0.6-0.75) for percentage decreases in SBP and MBP, respectively. Gray zone values with false-positive and negative rates <10% were SBP decreases of 20.5% and 37.5%, respectively, and MBP decreases of 15.5% and 44.5%, respectively. Our results indicate that falls in noninvasive systolic blood pressure of <20% from baseline are associated with a <10% chance of cerebral desaturation in neonates and infants <3 months of age undergoing noncardiac surgery. As such, maintaining systolic blood pressure above this threshold value appears a valid clinical target.


A long-term survival case of multiple hepatocellular carcinoma with metachronous lymph node metastasis.
A long-term survival case of multiple hepatocellular carcinoma (HCC) with metachronous metastasis to a lymph node is reported. The patient, a 66-year-old woman, had two primary HCC nodules, one each in the left and right hepatic lobes, which were resected. She developed a lymph node lesion and a secondary HCC 45 and 62 months after the first operation, respectively. She has been well for the 7 years since the first operation despite undergoing hepatic resection for HCC twice as well as lymph node resection. Clonal analysis, based on the methylation pattern of the X chromosome-linked androgen receptor gene, suggested that the two primary tumors were multicentric and that the lymph node lesion had arisen by metastasis from the primary tumor in the right hepatic lobe.


[Effects of neurectomy of the tympanic plexus on secretion of the parotid gland in man. Histopathological, histochemical and clinical study (author's transl)].
This study involved five patients suffering from bilateral chronic parotiditis and then with a persistent unilateral fistula of the parotid gland. Two types of parotid biopsy were examined: the first taken during surgery and the second six months later. All of the specimens underwent histopathological and histochemical investigations. Definitive degeneration and atrophic type changes were seen in all the parotid fragments removed six months after selective neurectomy of the tympanic plexus. Six months after surgery, all of the patients were cured.


Clinical diagnosis of multiple sclerosis. The impact of magnetic resonance imaging and ancillary testing. Rochester-Toronto Magnetic Resonance Study Group.
Magnetic resonance imaging, computed tomography, cerebrospinal fluid analysis, and evoked potential testing are used to assist in the diagnosis of patients suspected to have multiple sclerosis (MS). The impact of these tests on a clinician's diagnosis of patients suspected to have MS has not been studied systematically. Clinicians made a diagnosis of each patient following clinical evaluation, again after reviewing the results of magnetic resonance imaging, and finally after reviewing information from other laboratory testing. These diagnoses were compared with the criterion standard of a masked "gold standard" panel reviewing all information after a mean follow-up of 0.9 year. The General Neurology Clinic and Multiple Sclerosis Clinic of the University of Rochester (NY). A consecutive sample of 62 patients diagnosed as having either possible or probable MS following clinical evaluation. Changes in diagnostic certainty of clinicians following incremental presentation of new laboratory data and the accuracy of such diagnoses. Clinicians used magnetic resonance imaging findings to diagnose definite MS or to eliminate MS from diagnostic consideration in 44% of cases. In these cases, further laboratory testing did not alter clinicians' decisions. In the remaining 56% of cases, in which magnetic resonance imaging did not lead to a diagnosis of definite MS or eliminate MS from diagnostic consideration, further laboratory testing led to such diagnoses in an additional 13% of cases. Gold standard diagnoses were in agreement with the clinician's assessments. Magnetic resonance imaging aids in the evaluation of patients suspected to have MS; other subsequent studies (computed tomography, cerebrospinal fluid analysis, and evoked potential testing) have less impact. After all studies are performed, about half of such patients still have a tentative diagnosis.