Leprosy late-onset neuropathy: an uncommon presentation of leprosy.
Clinical and pathological findings in leprosy are determined by the natural host immune response to Mycobacterium leprae. We previously described cases of painful neuropathy (PN) with no concurrent cause apart from a past history of leprosy successfully treated. Four leprosy previously treated patients who developed a PN years after multidrug therapy (MDT) are reported. The mean patient age was 52.75 years (47-64). The mean time interval of the recent neuropathy from the previous MDT was 19 years (12-26). A painful multiplex neuritis or polyneuropathy were observed respectively in two cases. Electrophysiological studies disclosed a sensory axonal neuropathy in two cases. Microvasculitis with no bacilli was seen in nerve biopsy. Neuropathic symptoms were improved with prednisone. We consider these cases as being a leprosy late-onset neuropathy (LLON) form of presentation. A delayed immune reaction could explain the late appearance of LLON.


Prostate cancer and physical activity: adaptive response to oxidative stress.
Prostate cancer is the most common form of cancer affecting men in the Western world. Its relative incidence increases exponentially with age and a steady increase is observed with extended life span. A sedentary lifestyle represents an important risk factor and a decrease in prostate cancer prevalence is associated with exercise. However, the molecular mechanisms involved in this process remain unknown. We hypothesize that reactive oxygen species generated by physical exercise are a key regulatory factor in prostate cancer prevention. Aging is correlated with increased oxidative stress (OS), which in turn provides a favorable environment for tumorigenesis. Running training is known to enhance the antioxidant defense system, reducing oxidative stress. In this context, the decrease in OS induced by exercise may delay the development of prostate cancer. This review focuses on oxidative stress-based mechanisms leading to prostate cancer sensitization to exercise, which could have some impact on the development of novel cancer therapeutic strategies.


Controllable synthesis of two adenosine 5'-monophosphate nucleotide coordination polymers via pH regulation: crystal structure and chirality.
Two types of Cu(ii)-AMP-4,4'-bipy coordination polymers, {[Cu(AMP)(4,4'-bipy)(H2O)3]·5H2O}n (1) and {[Cu2(HAMP)2(4,4'-bipy)2(H2O)4]·2NO3·11H2O}n (2) (Na2AMP = adenosine 5'-monophosphate disodium salt), were synthesised through pH control. X-ray single-crystal diffraction analysis revealed that 1 and 2 are one-dimensional (1D) coordinating coordination polymers. The nucleotide in 1 was not protonated whereas that in 2 was protonated. With the protonated NO3- in 2 entering the crystal lattice, it plays a role in balancing the charge. The chirality was studied using solid-state circular dichroism (CD) spectroscopy based on the analysis of crystal structures.


The 100 Most Influential Papers in the Field of Thrombolytic Therapy: A Bibliometric Analysis.
Bibliometric analyses are used by researchers and research funding agencies to help determine areas of greatest interest, and consequently which topics and domains warrant increased research attention. Bibliometric analyses have similarly been published in a number of clinical subspecialties concerning areas of specific medical interest; however, a thorough literature search revealed that such a study has been absent in the field of thrombolytics to date. To bridge this gap, we conducted a citation analysis of the 100 most influential articles on thrombolytics. Scopus was selected as the database of choice. Two independent researchers explored the database to extract relevant articles. The articles were ranked according to the number of citations, and a sequential list of the top 100 original articles was prepared in descending order. A detailed analysis was carried out to identify trends and uncover significant discriminators. A second list containing the top 10 review articles was also separately prepared. The 100 most-cited articles regarding thrombolytics were published between 1973 and 2015, with the most articles (n = 29) published in the 5-year period extending from 1996 to 2000. The total number of citations of these 100 most-cited articles ranged from a low of 389 to a high of 6971, with a median of 612.5 citations. These 100 most-cited articles originated from 26 different countries, with more than half from the USA (n = 54), followed by the next most popular countries of origin Germany (n = 20) and France (n = 15). The New England Journal of Medicine (n = 26) and The Lancet (n = 26) contributed the majority of the articles. Our analysis provides insight into the span of research activity and the nature of inquiry dealing with 'thrombolytic therapy,' with the hope that such analysis may help to effectively guide future research. Our analysis also yielded a list of the most highly cited and presumably most impactful guideline articles within this field, for distinct consideration.


The Korsakoff syndrome: a neurochemical perspective.
Korsakoff's disease is an amnesic syndrome associated with midline diencephalic and brain stem pathology. A number of neurochemical systems course through or near the loci of brain lesions found postmortem in Korsakoff patients, which has stimulated studies to learn whether these systems are implicated in amnesia. Data suggest that the loss of brain catecholamine function contributes to this amnesic syndrome and may also be a factor in the memory impairments associated with normal aging. At present, data are insufficient to determine whether cholinergic systems are disturbed in Korsakoff's patients; however, it is likely that multiple neurochemical abnormalities underlie this disorder.


Neuroprotective therapy in Parkinson disease.
During the past decade, there has been a remarkable progress in our understanding of the biology of Parkinson disease (PD), which has been translated into searching for novel therapy for PD. Much focus is shifted from the development of drugs that only relieve PD symptoms to new generation of remedies that can potentially protect dopaminergic neurons and modify the disease course. Several novel therapeutic approaches have been tested in preclinical experiments and in clinical trials, including molecules targeting on genes involved in the pathogenesis of the disease, neurotrophic factors critical for dopaminergic neuron survival and function, new generation of dopamine receptor agonists that may possess neuroprotective effects, and agents of antioxidation, antiinflammation, and antiapoptosis. The results of these studies will shed new light to our hope that PD can be cured in the future.


Identification and characterization of the glutathione and N-acetylcysteine conjugates of (E)-2-propyl-2,4-pentadienoic acid, a toxic metabolite of valproic acid, in rats and humans.
The severe hepatotoxicity of valproic acid (VPA) is believed to be mediated through reactive metabolites. The formation of glutathione (GSH) and N-acetylcysteine (NAC) adducts of reactive intermediates derived from VPA and two of its metabolites, 2-propyl-4-pentenoic acid (4-ene-) and 2-propyl-2,4-pentadienoic acid [(E)-2,4-diene VPA], was investigated in the rat. Rats were dosed ip with 100 mg/kg of VPA, 4-ene-, or 2,4-diene-VPA, and methylated bile and urine extracts were analyzed by LC/MS/MS and GC/MS, respectively. The GSH conjugate of (E)-2,4-diene VPA was detected in the bile of rats treated with 4-ene- and (E)-2,4-diene VPA. The NAC conjugate was a major urinary metabolite of rats given (E)-2,4-diene VPA and was a prominent urinary metabolite of those animals given 4-ene VPA. The NAC conjugate was also found to be a metabolite of VPA in patients. Both the GSH and NAC adducts were chemically synthesized and their structures established to be 5-(glutathion-S-yl)3-ene VPA and 5-(N-acetylcystein-S-yl)3-ene VPA by NMR and mass spectrometry. In contrast to the very slow reaction of the free acid of (E)-2,4-diene VPA with GSH, the methyl ester reacted rapidly with GSH to yield the adduct. In vivo it appears the diene forms an intermediate with enhanced electrophilic reactivity to GSH as indicated by the facile reaction of the diene with GSH in vivo [about 40% of the (E)-2,4-diene VPA administered to rats was excreted as the NAC conjugate in 24 hr]. The characterization of the GSH and NAC (in humans and rats) conjugates of (E)-2,4-diene VPA suggests that VPA is metabolized to a chemically reactive intermediate that may contribute to the hepatotoxicity of the drug.


[The effect of hydrocortisone on the proliferative activity ureteral epithelial cells].
Autoradiography has demonstrated that a single injection of hydrocortisone (10mg/100 gm b.w.) reduced statistically significant the number of DNA synthesizing cells and the intensity of 3H-thymidine incorporation in these cells, as well as reduced the number of mitotically dividing epithelial cells in the rat ureter. 16 hours after hydrocortisone administration, the amount of proliferating cells increases statistically, but in 48 hours it reaches the control level.


Simultaneous diagnosis and resection of orofacial rhabdomyosarcoma with frozen section biopsy: a case report.
Rhabdomyosarcoma is the most common soft tissue sarcoma in children, accounting for 4.5% of all cases of cancer in childhood. Although the head and neck are the most common sites of rhabdomyosarcoma, oral lesions are relatively rare and account for only 10% to 12% of head and neck rhabdomyosarcoma cases. This is a case report of a girl aged 2 years and 1 month who initially presented with an upper lip mass that invaded the oral mucosa, oral skin, and nostril skin, causing narrowing of the airway. Through our case, we show that rapidly growing small round cell malignancies, especially rhabdomyosarcoma, can be effectively diagnosed and treated at the same time using primary resection with intraoperative frozen section biopsy and that the time spent waiting for the results of preoperative biopsy can be saved in this way, particularly when the patient's symptoms are intensifying rapidly and require immediate operation.


[Spectral analysis of some nutrients and minerals in Agaricus bisporus fruit bodies harvested at four different maturity stages].
The contents of nutritional elements such as Na, K, P, Ca, Mg and trace elements such as Cu, Se, Mo, Fe in Agaricus bisporus fruit bodies harvested at four different maturity stages (stage I, II, III, IV) were analyzed by ICP-AES, and the contents of some nutritional ingredients such as water, soluble protein, soluble sugar and ascorbic acid were also investigated. The results showed that the contents of Na, K, P, Mg, Cu, Se and Mo in stage I was respectively higher than those in the other three stages (alpha = 0.05), and the contents of Ca and Fe were respectively higher than those in stage II and III. The content of Se in stage IV was respectively higher than that in stage II and III, while the content f Na was respectively higher than that in stage II. The content of Cu in stage IV was respectively higher than that in stage III. The contents of K, P, Ca, Mg, Mo and Fe in stage II and III were respectively higher than those in stage IV. The content of water in stage IV was respectively higher than that in stage I and III, and had no significant differences from that in stage II. There were no significant differences in the contents of soluble protein, but the content of soluble sugar was significantly lower in stage IV. The content of ascorbic acid in stage III had no significant differences from that in stage I, but it was respectively higher than that in stage II and IV. The content of ascorbic acid in stage I and IV was respectively higher than that in stage II. The differences in the nutritional ingredients and mineral elements in the four stages of Agaricus bisporus fruit bodies provide academic data for the consumers and food industries while choosing Agaricus bisporus produces.


Conversion disorder in Australian pediatric practice.
To describe the incidence and clinical features of children presenting to Australian child health specialists with conversion disorder. Active, national surveillance of conversion disorder in children younger than 16 years of age during 2002 and 2003. A total of 194 children were reported on. The average age was 11.8 years; 23% were younger than 10 years of age. Presentations were complex, with 55% presenting with multiple conversion symptoms. The most common presentations were disturbance of voluntary motor function (64%), sensory symptoms (24%), pseudoseizure (23%), and respiratory problems (14%). Hospital admission was required for 70%, with an average stay of 10.2 days. Antecedent stressors were also reported in 62% and a history of mental health concerns in 42%, with 14% of children taking psychotropic medications for comorbid anxiety or depression. The incidence of conversion disorder in Australian specialist child health practice is estimated to be between 2.3 and 4.2/100,000. Conversion disorder is associated with a significant burden for the child, family, and the health system. This study emphasizes the comorbidity with anxiety, depression, and symptoms of pain and fatigue. It also highlights the potential impact of "commonplace" stressors such as family conflict and children's loss of attachment figures.


Protective Role of Hinokitiol Against H2O2-Induced Injury in Human Corneal Epithelium.
We recently found that hinokitiol has anti-inflammatory activity in human corneal epithelial (HCE) cells. Herein, we investigated the protective role of hinokitiol against H2O2-induced injury in HCE cells and the mechanisms that underlie its action. HCE cells were incubated with different concentrations of hinokitiol or dimethylsulfoxide (DMSO), which served as a vehicle control, before H2O2 stimulus. The cell viability was evaluated using a cell counting kit-8 (CCK-8) assay. TUNEL, phosphorylated histone γH2A.X, cleaved caspase-3 expression analyses, and location of cytochrome c were conducted to detect cell injury and apoptosis. Reactive oxygen species (ROS), catalase (CAT), superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), and total antioxidative capacity (T-AOC) were used to determine oxidative stress. Bcl-2 and Bax protein expressions were measured by western blotting. Hinokitiol significantly improved the cell viability, decreased the apoptosis rate, inhibited DNA damage, and reduced cleaved caspase-3 expression and the leakage of cytochrome c from mimitochondrion to cytoplasm of HCE cells against the oxidative stress induced by H2O2. Generation of ROS and MDA and decreased activity of CAT, SOD, and T-AOC were also ameliorated by hinokitiol administration. Moreover, Bcl-2 expression was down-regulated while Bax was up-regulated by H2O2 stimulus, which were reversed by hinokitiol application. Hinokitiol protects HCE cells against H2O2-induced injury likely by its antioxidant activity and modulating the Bcl-2 signaling pathway.


Measurement of Ion Concentration in the Unstirred Boundary Layer with Open Patch-Clamp Pipette: Implications in Control of Ion Channels by Fluid Flow.
Fluid flow is an important environmental stimulus that controls many physiological and pathological processes, such as fluid flow-induced vasodilation. Although the molecular mechanisms for the biological responses to fluid flow/shear force are not fully understood, fluid flow-mediated regulation of ion channel gating may contribute critically. Therefore, fluid flow/shear force sensitivity of ion channels has been studied using the patch-clamp technique. However, depending on the experimental protocol, the outcomes and interpretation of data can be erroneous. Here, we present experimental and theoretical evidence for fluid flow-related errors and provide methods for estimating, preventing, and correcting these errors. Changes in junction potential between the Ag/AgCl reference electrode and bathing fluid were measured with an open pipette filled with 3 M KCl. Fluid flow could then shift the liquid/metal junction potential to approximately 7 mV. Conversely, by measuring the voltage shift induced by fluid flow, we estimated the ion concentration in the unstirred boundary layer. In the static condition, the real ion concentrations adjacent to the Ag/AgCl reference electrode or ion channel inlet at the cell-membrane surface can reach as low as approximately 30% of that in the flow condition. Placing an agarose 3 M KCl bridge between the bathing fluid and reference electrode may have prevented this problem of junction potential shifting. However, the unstirred layer effect adjacent to the cell membrane surface could not be fixed in this way. Here, we provide a method for measuring real ion concentrations in the unstirred boundary layer with an open patch-clamp pipette, emphasizing the importance of using an agarose salt-bridge while studying fluid flow-induced regulation of ion currents. Therefore, this novel approach, which takes into consideration the real concentrations of ions in the unstirred boundary layer, may provide useful insight on the experimental design and data interpretation related to fluid shear stress regulation of ion channels.


Which treatment options should be used in adolescents with polycystic ovary syndrome?
Several studies have hypothesized a peripubertal onset of polycystic ovary syndrome (PCOS). This syndrome affects different pathogenetic pathways and includes endocrine-metabolic abnormalities such as hyperandrogenism, hyperinsulinism and insulin resistance. The therapeutic approaches must be addressed to individualization of therapy, considering the major clinical manifestations of the syndrome during adolescence. While the treatment of hyperandrogenism makes use of different drugs already studied, the debate about the use of insulin sensitizing drugs is still open. It will be more and more necessary to define the phenotypic and genotypic milieu in which all treatments will be as safe and effective as possible.


Pulmonary rehabilitation for COPD. A practical approach for improving ventilatory conditioning.
Pulmonary rehabilitation has gradually become the "gold standard" for patients with severe lung disease, especially chronic obstructive pulmonary disease (COPD). Because some newer therapeutic strategies, such as lung volume reduction surgery and lung transplantation, require well-conditioned patients, pulmonary rehabilitation is now considered essential for many patients formerly deemed untreatable. In this article, Dr Celli reviews the basic goals, components, and benefits of pulmonary rehabilitation for COPD and other chronic respiratory diseases.


Enzymatic synthesis of bioactive compounds with high potential for cosmeceutical application.
Cosmeceuticals are cosmetic products containing biologically active ingredients purporting to offer a pharmaceutical therapeutic benefit. The active ingredients can be extracted and purified from natural sources (botanicals, herbal extracts, or animals) but can also be obtained biotechnologically by fermentation and cell cultures or by enzymatic synthesis and modification of natural compounds. A cosmeceutical ingredient should possess an attractive property such as anti-oxidant, anti-inflammatory, skin whitening, anti-aging, anti-wrinkling, or photoprotective activity, among others. During the past years, there has been an increased interest on the enzymatic synthesis of bioactive esters and glycosides based on (trans)esterification, (trans)glycosylation, or oxidation reactions. Natural bioactive compounds with exceptional theurapeutic properties and low toxicity may offer a new insight into the design and development of potent and beneficial cosmetics. This review gives an overview of the enzymatic modifications which are performed currently for the synthesis of products with attractive properties for the cosmeceutical industry.


Ultra-wide-field imaging in diabetic retinopathy.
Since 1991, 7-field images captured with 30-50 degree cameras in the Early Treatment Diabetic Retinopathy Study were the gold standard for fundus imaging to study diabetic retinopathy. Ultra-wide-field images cover significantly more area (up to 82%) of the fundus and with ocular steering can in many cases image 100% of the fundus ("panretinal"). Recent advances in image analysis of ultra-wide-field imaging allow for precise measurements of the peripheral retinal lesions. There is a growing consensus in the literature that ultra-wide-field imaging improves detection of peripheral lesions in diabetic retinopathy and leads to more accurate classification of the disease. There is discordance among studies, however, on the correlation between peripheral diabetic lesions and diabetic macular edema and optimal management strategies to treat diabetic retinopathy.


Unwarranted Variation in the Quality of Care for Patients With Diseases of the Thoracic Aorta.
Thoracic aortic disease has a high mortality. We sought to establish the contribution of unwarranted variation in care to regional differences in outcomes observed in patients with thoracic aortic disease in England. Data from the Hospital Episode Statistics (HES) and the National Adult Cardiac Surgery Audit (NACSA) were extracted. A parallel systematic review/meta-analysis through December 2015, and structure and process questionnaire of English cardiac surgery units were also accomplished. Treatment and mortality rates were investigated. A total of 24 548 adult patients in the HES study, 8058 in the NACSA study, and 103 543 from a total of 33 studies in the systematic review were obtained. Treatment rates for thoracic aortic disease within 6 months of index admission ranged from 7.6% to 31.5% between English counties. Risk-adjusted 6-month mortality in untreated patients ranged from 19.4% to 36.3%. Regional variation persisted after adjustment for disease or patient factors. Regional cardiac units with higher case volumes treated more-complex patients and had significantly lower risk-adjusted mortality relative to low-volume units. The results of the systematic review indicated that the delivery of care by multidisciplinary teams in high-volume units resulted in better outcomes. The observational analyses and the online survey indicated that this is not how services are configured in most units in England. Changes in the organization of services that address unwarranted variation in the provision of care for patients with thoracic aortic disease in England may result in more-equitable access to treatment and improved outcomes.


Interplay of the Organic Cation Transporters OCT1 and OCT2 with the Apically Localized Export Protein MATE1 for the Polarized Transport of Trospium.
The anticholinergic drug trospium is secreted into urine and, to a smaller extent, into bile. Chemically, it is an organic cation, and it is a substrate of the uptake transporters OCT1 and OCT2 as well as for the export proteins MATE1 and MATE2-K as determined in uptake studies using HEK293 cells. So far, neither MATE-mediated export nor the interplay of OCT-mediated uptake and MATE-mediated export have been investigated. Therefore, we used polarized monolayers of single- and double-transfected MDCKII cells (MDCK-OCT1, MDCK-OCT2, MDCK-MATE1, MDCK-OCT1-MATE1, and MDCK-OCT2-MATE1) and the respective control cells (MDCK-Co) for transcellular transport assays. We demonstrate that the transcellular, basal-to-apical transport of trospium is significantly higher in all cell lines compared to control cells over nearly the complete concentration range tested. The transcellular transport mediated by double-transfected MDCK-OCT1-MATE1 and MDCK-OCT2-MATE1 exceeded that in the single-transfected cells (MDCK-OCT1-MATE1 vs MDCK-OCT1: 2.2-fold; MDCK-OCT1-MATE1 vs MDCK-MATE1: 1.7-fold; MDCK-OCT2-MATE1 vs MDCK-OCT2: 6.1-fold; MDCK-OCT2-MATE1 vs MDCK-MATE1: 1.8-fold at a trospium concentration of 1.0 μM; p < 0.001 each). Thus, we show that MATE1 does not only mediate the uptake of trospium into HEK293 cells but also the efflux of trospium out of polarized MDCKII-cells. Furthermore, our results indicate that OCT1 or OCT2 as uptake transporters and MATE1 as an export protein contribute to the transcellular transport of trospium at concentrations normally reached during trospium therapy. These data suggest that both, OCT-mediated uptake as well as MATE1-mediated efflux may contribute to trospium renal and biliary elimination.


Irradiation of the whole neuraxis. A method for field positioning.
When the whole neuraxis is irradiated, as in medulloblastoma, the large target volume makes field arrangement complicated and 3-4 adjacent fields have to be used. A calculation method, based on geometrical matching of field edges, is presented for determining optimal separation between the opposed cranial fields and the posterior spinal field as orthogonal movements of the treatment couch top. The dosimetric verification of the method with a 4 MV photon beam indicates a dose inhomogeneity below +/- 7%.


Dissecting the roles of the nuclear and mitochondrial genomes in a mouse model of autoimmune diabetes.
Mitochondria, the organelles responsible for generating ATP in eukaryotic cells, have been previously implicated as a contributor to diabetes. However, mitochondrial proteins are encoded by both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). In order to better understand the relative contribution of each of these genomes to diabetes, a chimeric mitochondrial-nuclear exchange (MNX) mouse was created via pronuclear transfer carrying nDNA from a strain susceptible to type 1 diabetes (NOD/ShiLtJ) and mtDNA from non-diabetic C57BL/6J mice. Inheritance of the resulting "heteroplasmic" mtDNA mixture was then tracked across multiple generations, showing that offspring heteroplasmy generally followed that of the mother, with occasional large shifts consistent with an mtDNA "bottleneck" in the germline. In addition, the survival and incidence of diabetes for MNX mice was tracked and compared to unaltered NOD/ShiLtJ control mice. The results indicate improved survival and a delay in diabetes onset in the MNX mice, demonstrating that the mtDNA holds a critical influence on the disease phenotype. Finally, enzyme activity assays showed that the NOD/ShiLtJ mice have a significant hyperactivity of complex I of the ETC relative to MNX mice, suggesting that a particular mtDNA variant (m.9461T>C) may be responsible for the disease causation in the original NOD/ShiLtJ strain.


Charge-Tagged Nucleosides in the Gas Phase: UV-Vis Action Spectroscopy and Structures of Cytidine Cations, Dications, and Cation Radicals.
Cytidine ribonucleosides were furnished at O5' with fixed-charge 6-trimethylammoniumhexan-1-aminecarbonyl tags and studied by UV-vis photodissociation action spectroscopy in the gas phase to probe isolated nucleobase chromophores in their neutral, protonated, and hydrogen-adduct radical forms. The action spectrum of the doubly charged cytidine conjugate showed bands at 310 and 270 nm that were assigned to the N3- and O2-protonated cytosine tautomers formed by electrospray, respectively. In contrast, cytidine conjugates coordinated to dibenzo-18-crown-6-ether (DBCE) in a noncovalent complex were found to strongly favor protonation at N3, forming a single-ion tautomer. This allowed us to form cytidine N3-H radicals by electron transfer dissociation of the complex and study their action spectra. Cytidine radicals showed only very weak absorption in the visible region of the spectrum for dipole-disallowed transitions to the low (A and B) excited states. The main bands were observed at 360, 300, and 250 nm that were assigned with the help of theoretical vibronic spectra obtained by time-dependent density functional theory calculations of multiple (>300) radical vibrational configurations. Collision-induced dissociations of cytidine radicals proceeded by major cleavage of the N1-C1' glycosidic bond leading to loss of cytosine and competitive loss of N3-hydrogen atom. These dissociations were characterized by calculations of transition-state structures and energies using combined Born-Oppenheimer molecular dynamics and DFT calculations. Overall, cytidine radicals were found to be kinetically and thermodynamically more stable than previously reported analogous adenosine and guanosine radicals.


[Dysphonia: current methods of evaluation].
The aim of this review article was to provide an update on current techniques for evaluation of dysphonia in routine clinical practice. Recent medical and other scientific literature was reviewed and pertinent current theories concerning the physiology of laryngeal function described. Perceptual voice quality evaluation by a professional jury of listeners is still considered to be the most reliable and complete means of evaluating pathologic voice, even though it is difficult to perform in routine and the results lack reproducibility. The objective evaluation of the vocal fundamental frequency and its variations and the spectral characteristics of voice has the advantage of being simple to perform, reproducible and quantifiable. However, automatic measurements need to be analyzed with precaution for severe dysphonia, the computer algorithms being designed for voices retaining a certain periodicity. Aerodynamic measurements are quantifiable and reproducible and provide information as to the quality of laryngeal function as a transducer of aerodynamic energy into acoustic energy. Videostroboscopy and electroglottography provide information as to the quality of the laryngeal vibrations, the source of sound production. All of these types of analysis are complementary, informing as to different aspects of vocal quality and laryngeal function. No one measurement alone can diagnose or characterize dysphonia.


The electronic McPhail trap.
Certain insects affect cultivations in a detrimental way. A notable case is the olive fruit fly (Bactrocera oleae (Rossi)), that in Europe alone causes billions of euros in crop-loss/per year. Pests can be controlled with aerial and ground bait pesticide sprays, the efficiency of which depends on knowing the time and location of insect infestations as early as possible. The inspection of traps is currently carried out manually. Automatic monitoring traps can enhance efficient monitoring of flying pests by identifying and counting targeted pests as they enter the trap. This work deals with the hardware setup of an insect trap with an embedded optoelectronic sensor that automatically records insects as they fly in the trap. The sensor responsible for detecting the insect is an array of phototransistors receiving light from an infrared LED. The wing-beat recording is based on the interruption of the emitted light due to the partial occlusion from insect's wings as they fly in the trap. We show that the recordings are of high quality paving the way for automatic recognition and transmission of insect detections from the field to a smartphone. This work emphasizes the hardware implementation of the sensor and the detection/counting module giving all necessary implementation details needed to construct it.


[Synaptogenesis and formation of benzodiazepine receptors in the human brain in conditions of prenatal alcoholization].
The aim was to study correlations between the development of synaptic connections and benzodiazepine receptors functionally linked to the brain GABA system in the brain of embryos and 8-15 week fetuses obtained from women with alcoholism. Material from 33 women with alcoholism, stage II (ICD-10 F10.201 and F10.202), and 30 healthy people (controls) was studied. The retardation in the formation of synaptic benzodiazepine receptors and increase in their density was seen in brain cells developing in conditions of prenatal alcoholization compared to controls. The authors consider these findings as a manifestation of compensatory reactions directed towards the adaptation of the fetal nervous system to the action of alcohol and as functional insufficiency of the brain GABA system.


Kunxian capsule alleviates podocyte injury and proteinuria by inactivating β-catenin in db/db mice.
Diabetic kidney disease (DKD) remains the primary cause of end-stage renal disease (ESRD) globally, but treatment options are limited. Kunxian capsule (KXC) has been utilized for the treatment of autoimmune diseases and IgA nephropathy in China. However, its effect on DKD remains poorly investigated. Therefore, this study aimed to explore the protective effect of KXC in db/db mice and elucidate its underlying mechanism. The renoprotective effects of KXC were assessed in a DKD mouse model using male BKS db/db diabetic mice. After 8 weeks of treatment, the urinary albumin-to-creatinine ratio (UACR), blood biochemical parameters, renal histopathological manifestation, and podocyte ultrastructural changes were evaluated. Additionally, the expression of podocyte epithelial-to-mesenchymal transition (EMT) markers [WT1, ZO-1, and collogen I (Col1a1)] was quantitatively analyzed. Furthermore, we explored the role of KXC in the β-catenin signaling pathway to elucidate the underlying mechanism of KXC's renoprotective effect. KXC treatment effectively reduced albuminuria and attenuated renal structural abnormalities in db/db mice. Additionally, KXC restored the protein and mRNA expression of WT1 and ZO-1 while suppressing the expression of Col1a1 in db/db mice, indicating its ability to alleviate podocyte EMT. Mechanistically, KXC exerted a significant suppressive effect on the activation of β-catenin signaling in diabetic kidneys. KXC has the potential to protect podocytes during DKD by alleviating podocyte EMT through inactivating β-catenin signaling.


The role and spectrum of SLC26A4 mutations in Iranian patients with autosomal recessive hereditary deafness.
To determine the prevalence and types of SLC26A4 mutations and the relevant phenotypes in a series of Iranian deaf patients. A descriptive laboratory study. One hundred and twenty-one families including 60 unrelated patients and 61 unrelated multiplex families with autosomal recessive deafness were included. In the 61 multiplex families, linkage was conducted for short tandem repeats (STRs) of the DFNB4. Selected individuals from the linked families and all of the 60 deaf individuals were subjected to sequencing of SLC26A4. Seven out of the 61 (11.5%) families were linked to the locus which upon further inquiry led to identification of eight different mutations. Also, five out of the 60 (8.3%) patients were positive for the mutations. The SLC26A4 mutations clarified in 9.1% (12 families) of total investigated alleles included: c.2106delG, c.65-66insT, c.881-882delAC, c.863-864insT, c.1226G> A, c.1238A> G, c.1334T> G, c.1790T> C, c.1489G> A, c.919-2A> G (IVS7-2A> G), c.1412delT, and c.1197delT. Six out of 12 (50%) families with mutations were confirmed to be Pendred syndrome (PS). The results probably suggest a high prevalence and specificity of SLC26A4 mutations among Iranian deaf patients. Molecular study of SLC26A4 may lead to elucidation of the population-specific mutation profile which is of importance in diagnostics of deafness.


Multi-Light-Responsive Upconversion-and-Downshifting-Based Circularly Polarized Luminescent Switches in Chiral Metal-Organic Frameworks.
Metal-organic frameworks (MOFs) have attracted tremendous attention for several novel applications. However, functional MOFs with light-responsive circularly polarized luminescence (CPL) are not examined in detail. Therefore, a dual CPL switch exhibiting both upconversion (UC) and downshifting (DS) CPL in the solid state is constructed by loading a luminescent diarylethene derivative (DAEC) and UC nanoparticles (UCNPs) into chiral MOFs. The chiral MOF⊃DAEC composites exhibit both photoswitchable luminescence and DS-CPL properties under alternating UV and visible light irradiation. Additionally, a reversible UC-CPL switch is realized using near-infrared (NIR) and visible light irradiation by introducing energy-level-matched UCNPs and DAEC into the chiral MOFs. The dissymmetry factor (glum ) of UC-CPL is noted to be significantly amplified through energy transfer compared to that of DS-CPL, which indicates that the information on circular polarization can be manipulated by altering the incident light. A chiroptical logic circuit with a 2D information output is designed with UV, visible, and NIR light as inputs by setting a rational threshold.


Genome-Wide Association Study Using Whole-Genome Sequencing Identifies a Genomic Region on Chromosome 6 Associated With Comb Traits in Nandan-Yao Chicken.
Comb traits have potential economic value in the breeding of indigenous chickens in China. Identifying and understanding relevant molecular markers for comb traits can be beneficial for genetic improvement. The purpose of this study was to utilize genome-wide association studies (GWAS) to detect promising loci and candidate genes related to comb traits, namely, comb thickness (CT), comb weight (CW), comb height, comb length (CL), and comb area. Genome-wide single-nucleotide polymorphisms (SNPs) and small insertions/deletions (INDELs) in 300 Nandan-Yao chickens were detected using whole-genome sequencing. In total, we identified 134 SNPs and 25 INDELs that were strongly associated with the five comb traits. A remarkable region spanning from 29.6 to 31.4 Mb on chromosome 6 was found to be significantly associated with comb traits in both SNP- and INDEL-based GWAS. In this region, two lead SNPs (6:30,354,876 for CW and CT and 6:30,264,318 for CL) and one lead INDEL (a deletion from 30,376,404 to 30,376,405 bp for CL and CT) were identified. Additionally, two genes were identified as potential candidates for comb development. The nearby gene fibroblast growth factor receptor 2 (FGFR2)-associated with epithelial cell migration and proliferation-and the gene cytochrome b5 reductase 2 (CYB5R2)-identified on chromosome 5 from INDEL-based GWAS-are significantly correlated with collagen maturation. The findings of this study could provide promising genes and biomarkers to accelerate genetic improvement of comb development based on molecular marker-assisted breeding in Nandan-Yao chickens.


Residential accessibility to information technology retailers and self reported computer use among patients attending community clinics.
The actual mechanisms that maintain the individual disparities in home computer use and internet access that are collectively termed "the digital divide" remain unclear. We hypothesized that geographic accessibility to IT retailers would independently influence community clinic patients self reported use of computers at home thus limiting their ability to access health related information via the internet. To test this we obtained information on the locations of IT retailers in Los Angeles County, California and generated accessibility scores for the patient's home residence. Geographic measures of accessibility to IT retailers independently predicted clinic patient's self reported use of computers at home, and this effect was driven by low income individuals. Our results indicate that the causes of the digital divide are influenced by less commonly considered factors such as local IT retailer availability.


Regulation of NAD(P)H oxidase by associated protein disulfide isomerase in vascular smooth muscle cells.
NAD(P)H oxidase, the main source of reactive oxygen species in vascular cells, is known to be regulated by redox processes and thiols. However, the nature of thiol-dependent regulation has not been established. Protein disulfide isomerase (PDI) is a dithiol/disulfide oxidoreductase chaperone of the thioredoxin superfamily involved in protein processing and translocation. We postulated that PDI regulates NAD(P)H oxidase activity of rabbit aortic smooth muscle cells (VSMCs). Western blotting confirmed robust PDI expression and shift to membrane fraction after incubation with angiotensin II (AII, 100 nm, 6 h). In VSMC membrane fraction, PDI antagonism with bacitracin, scrambled RNase, or neutralizing antibody led to 26-83% inhibition (p < 0.05) of oxidase activity. AII incubation led to significant increase in oxidase activity, accompanied by a 6-fold increase in PDI refolding isomerase activity. AII-induced NAD(P)H oxidase activation was inhibited by 57-71% with antisense oligonucleotide against PDI (PDIasODN). Dihydroethidium fluorescence showed decreased superoxide generation due to PDIasODN. Confocal microscopy showed co-localization between PDI and the oxidase subunits p22(phox), Nox1, and Nox4. Co-immunoprecipitation assays supported spatial association between PDI and oxidase subunits p22(phox), Nox1, and Nox4 in VSMCs. Moreover, in HEK293 cells transfected with green fluorescent protein constructs for Nox1, Nox2, and Nox4, each of these subunits co-immunoprecipitated with PDI. Akt phosphorylation, a known downstream pathway of AII-driven oxidase activation, was significantly reduced by PDIasODN. These results suggest that PDI closely associates with NAD(P)H oxidase and acts as a novel redox-sensitive regulatory protein of such enzyme complex, potentially affecting subunit traffic/assembling.


New halogenated disinfection byproducts in swimming pool water and their permeability across skin.
Chlorine is widely used for disinfecting public swimming pool water. The disinfectant chlorine, protecting swimmers from pathogenic infection in swimming, may be responsible for some adverse effects on swimmers' skin and health. In this study, numerous new halogenated disinfection byproducts (DBPs) in chlorinated pool water were detected with a powerful precursor ion scan method using electrospray ionization triple quadrupole mass spectrometry, with or without preseparation with ultra performance liquid chromatography. These new pool DBPs were demonstrated to be mainly halo(nitro)phenols, resulting from chlorination of human body substances (such as urine) in the presence of bromide. Among these new DBPs, 2,4-dibromophenol, 2,4-dichlorophenol, 2-bromophenol, 2,6-dibromo-4-nitrophenol, 2-bromo-6-chloro-4-nitrophenol, and 2,6-dichloro-4-nitrophenol were fully identified or confirmed. For 2,4-dibromophenol, 2,4-dichlorophenol and 2-bromophenol with pure standard compounds available, their permeability values across human skin were measured to be 0.031, 0.021, and 0.023 cm/h, respectively. The effects of chlorine on human skin were also investigated. The interaction of chlorine with epidermis was found to generate many new halogenated DBPs as well as common DBPs; the corneous layer was observed to become rough and even form larger pores after chlorine interaction. It is recommended that swimmers should avoid urinating in pools, and avoid prolonged swimming to reduce chlorine contact and prevent accelerated permeation of DBPs across skin.


Muon g-2 and B Anomalies from Dark Matter.
In light of the recent result of the muon g-2 experiment and the update on the test of lepton flavor universality R_{K} published by the LHCb Collaboration, we systematically study for the first time a set of models with minimal field content that can simultaneously give (i) a thermal dark matter candidate; (ii) large loop contributions to b→sℓℓ processes able to address R_{K} and the other B anomalies; (iii) a natural solution to the muon g-2 discrepancy through chirally enhanced contributions. Moreover, this type of model with heavy particles and chiral enhancement can evade the strong limits from direct searches but can be tested at present and future colliders and direct-detection searches.


The functional consequences of airway remodeling in asthma.
Structural changes in the airway walls involving extracellular matrix remodelling are prominent features of asthma. These changes are probably driven by mediators released as a consequence of chronic allergic inflammation. It is clear that changes in the extracellular matrix have the capacity to influence airway function in asthma. However, it is not clear how each of the many changes that occur in the airway wall contribute to altered airway function in asthma. Collagen deposition in the subepithelial matrix, and hyaluronan and versican deposition around and internal to the smooth muscle would be expected to oppose the effect of smooth muscle contraction. Conversely, geometric considerations would result in exaggerated airway narrowing for a given degree of smooth muscle shortening, as the airway wall is thickened by the deposition of these molecules internal to the smooth muscle. Elastin and cartilage reorganization and degradation in the airway walls would be expected to result in decreased airway wall stiffness and increased airway narrowing for a given amount of force generated by the smooth muscle. Degradation of matrix associated with the smooth muscle may both decrease the stiffness of the parallel elastic component and uncouple smooth muscle from the load provided by lung recoil, allowing exaggerated smooth muscle shortening. Increase in muscle mass may be associated with an increase, a decrease or no change in smooth muscle contractility. If an increase in muscle mass was associated with preservation of its contractile capacity modelling studies suggest that it could be the most important contributor to exaggerated airway narrowing. Modelling studies also suggest that the pattern of mucosal folding during smooth muscle contraction may be an important determinant of airway narrowing. The greater the number of folds, and the stiffer the subepithelial collagenous layer the more resistant the airway will be to narrowing.


Fibulin-4 deposition requires EMILIN-1 in the extracellular matrix of osteoblasts.
Tissue microenvironments formed by extracellular matrix networks play an important role in regulating tissue structure and function. Extracellular microfibrillar networks composed of fibrillins and their associated ligands such as LTBPs, fibulins, and EMILINs are of particular interest in this regard since they provide a specialized cellular microenvironment guiding proper morphology and functional behavior of specialized cell types. To understand how cellular microenvironments composed of intricate microfibrillar networks influence cell fate decisions in a contextual manner, more information about the spatiotemporal localization, deposition, and function of their components is required. By employing confocal immunofluorescence and electron microscopy we investigated the localization and extracellular matrix deposition of EMILIN-1 and -2 in tissues of the skeletal system such as cartilage and bone as well as in in vitro cultures of osteoblasts. We found that upon RNAi mediated depletion of EMILIN-1 in primary calvarial osteoblasts and MC3T3-E1 cells only fibulin-4 matrix deposition was lost while other fibulin family members or LTBPs remained unaffected. Immunoprecipitation and ELISA-style binding assays confirmed a direct interaction between EMILIN-1 and fibulin-4. Our data suggest a new function for EMILIN-1 which implies the guidance of linear fibulin-4 matrix deposition and thereby fibulin-4 fiber formation.


Reduced hippocampal dendritic spine density and BDNF expression following acute postnatal exposure to di(2-ethylhexyl) phthalate in male Long Evans rats.
Early developmental exposure to di(2-ethylhexyl) phthalate (DEHP) has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats.


Chewing and Swallowing Abilities of Persons Living With Dementia: A Systematic Review of Psychometric Properties of Instruments.
It is critical to use validated instruments to diagnose and manage chewing and swallowing problems of persons living with dementia. The study aimed to synthesize the characteristics and psychometric quality of instruments that assess the chewing and swallowing abilities of persons living with dementia. The systematic review was used to conduct this study. We searched 5 electric databases for records published from January 1, 1980, to July 8, 2022. Records were eligible if they included any instrument to assess chewing ability or swallowing ability in the dementia population. Eight characteristics of eligible instruments were extracted from the records: (1) development process, (2) operationalized concept/construct, (3) sample and setting, (4) administration method, (5) items, (6) scoring format/interpretation, (7) reliability, and (8) validity. The psychometric assessment for self-report and observational tool was used to evaluate 12 psychometric properties of eligible instruments. In total, 11,074 records were reviewed. Thirty-five eligible instruments, including observational tools, self-report questionnaires, and physiological instruments, were identified from 60 records. All 8 instruments assessing chewing ability were evaluated as having low psychometric quality, and only 3 out of 27 instruments assessing swallowing ability were evaluated as having moderate psychometric quality. Fifteen instruments were tested for only 1 type of psychometric property, limiting the overall evaluation of psychometric evidence. The study findings inform the use and adaptation of appropriate instruments for practice and research. All existing instruments warrant further validation in larger samples to expand use in diverse care settings. This review described and evaluated current instruments measuring chewing and swallowing abilities and potential use in research and clinical practice to plan for and evaluate the effectiveness of mealtime and oral care practice and reduce health-related negative outcomes of persons living with dementia.


Comparisons of wound healing among excisional, laser-created, and standard thermal burns in porcine wounds of equal depth.
The present study was designed to characterize similarities and differences among three wounding modalities in partial-thickness porcine wounds. We hypothesized that inherent differences, such as endogenous cytokine delivery into excisional wounds or ablation of eschar during laser vaporization, should accelerate the magnitude and sequence of reparative events above the delayed repair that is frequently observed in patients with burns. A constant mid-dermal depth of injury was created by a Padgett dermatome, a computer-controlled pulsed CO(2) laser, or a temperature-controlled metal template. Wounds were harvested after 5, 10, or 15 days. After 5 days, significant resurfacing differences were apparent with values of 54% in excisions, 29% in lasers, and 12% in standard thermal burns. Sequences of fibroblastic proliferation were measurably different among the three wound modalities. At day 5 the bromodeoxyuridine labeling index for fibroblasts showed laser wound levels greater than excision wound levels, which were greater than burn wound levels; but by day 10, the proliferative profiles indicated that burn wound levels were greater than excision wound levels, which were greater than laser wound levels. Capillary areas (an assessment of angiogenesis) differed among the three wound types throughout the study. Peak values were observed at day 5 in both excisional and laser injuries; however, standard thermal burns did not peak until day 10. Both the magnitude and sequence of expression of three matrix metalloproteinases (-1, -2, and -9) differed among the three types of injuries. Laser wounds showed the earliest peak in matrix metalloproteinase-1 expression, whereas burns showed the least expression at day 5. In conclusion, although the three types of wounds undergo similar reparative processes such as reepithelialization, fibroblastic proliferation, angiogenesis, and expression of matrix metalloproteinases, the magnitude and temporal sequences are measurably altered among the three wound modalities. A greater understanding of specific differences within wound environments may lead to more insightful design of interventional wound therapies.


A rare case report of acyclovir-induced immune thrombocytopenia with tongue hematomas as the first sign, and a literature review.
Acyclovir has been widely used to treat infections caused by herpes simplex virus (HSV) and varicella zoster virus (VZV). The common adverse effects of this drug include nausea, diarrhea, headache, dizziness and mental changes. The immune thrombocytopenia induced by acyclovir is rare. A 67-year-old Chinese male who was given acyclovir 5 mg kg-1 8 hourly intravenously for treatment of VZV infection developed severe thrombocytopenia with fist sign in oral cavity within 10 days of starting using acyclovir. The patient's condition was improved by stopping using acyclovir and further supportive treatment. The acyclovir-dependent platelet antibody test showed positive results, which implicated acyclovir as the causative agent. The final definitive diagnosis of acyclovir-induced immune thrombocytopenia was established basing on the time correlation between the start of using acyclovir and the onset of symptoms of thrombocytopenia, combining with excluding of other common causes of thrombocytopenia. There have been few reports of acyclovir-induced immune thrombocytopenia. This is the first case report and literature review of acyclovir-induced immune thrombocytopenia, with tongue hematoma as the first sign. Dentists should never overlook this rare adverse effect of acyclovir, as a rapid and appropriate treatment may prevent further severe life-threatening complications.


Psychometric functions for hybrid difference discrimination/increment detection tasks.
Psychometric functions collected from difference discrimination tasks typically have slopes near 1, whereas those from increment detection tasks have slopes near 2. Experiments exploring the effect of stimulus configuration on the psychometric function were undertaken. Some stimuli were configured to conform to difference discrimination and increment detection tasks, while other "hybrid" stimulus configurations had physical properties associated with both tasks. The results suggest that these hybrid configurations may have psychophysical properties that fall in between those found for difference discrimination and increment detection tasks.


Opening contraction energy in prostatic (compressive) obstruction.
The opening contraction energy (Eop), i.e. the energy expended by the detrusor in the opening phase of micturition, was measured in 70 males (mean age 63 +/- 9 years) with bladder outflow obstruction (compressive obstruction) due to benign prostatic hypertrophy. Significant correlations (p less than 0.001) were found between Eop and the maximum external voiding power developed by the detrusor, Wext max (rs = -0.57), between Wext max and the fraction of bladder volume voided, VV% (rs = 0.65), and between Eop and VV% (rs = -0.77) - which suggests that increasing values of Eop affect the energy which the detrusor can supply for completion and termination of voiding. It then seems the parameter Eop would be able to assess not only the opening phase of micturition, but the emptying phase as well - the greater Eop (i.e. the greater the work needed to unfold the urethral lumen and start urine flow), the lesser the muscle mechanical capability of the urinary bladder to completely void. Thus, we eventually believe that calculating the parameter Eop may prove to be a complete, though indirect, method of quantifying the degree of prostatic (compressive) obstruction of the vesical outlet by a single numerical index.


Highly effective expression of glutamine synthetase genes GS1 and GS2 in transgenic rice plants increases nitrogen-deficiency tolerance.
Glutamine synthetase (GS, EC126.96.36.199) is a key enzyme in ammonia assimilation both in plants and in Gram-negative microorganisms. It plays an important role in efficient use of nitrogen sources and nitrogen metabolism in organisms. Two groups of GS isoenzymes, plastidic (GS2) and cytosolic (GS1), have been identified in higher plants. A plant constitutive expression vector p2GS harboring GS1 and GS2 under the control of rice actin 1 (Act1) and maize ubiquitin (Ubi) promoters was constructed for the first time in a single plasmid, and 3 rounds of ligation and transformation were performed. There has been no report about studies on rice transformation with the two GS enzymes (GS1 and GS2). The p2GS thus constructed was introduced into rice var. Zhonghua 10 by Agrobacterium-mediated transfer method, and transgenic plants with resistance to hygromycin (Hyg) were obtained. Results of PCR and Southern blot analysis showed that the foreign genes have been integrated into the rice genome. The transcription of GS1-GS2 genes in the transformants was also confirmed by Northern blot analysis. The transgenic rice plants thus obtained can grow well in an MS medium in which the nitrogen source was replaced by (NH(4))(2)SO(4) 0.7 mmol/L, and fresh weight of the transformants was significantly higher than the control rice plants. The result suggests that expression of p2GS makes the transgenic rice plants tolerant to nitrogen-deficiency.


Cloning, expression, and biological activity of recombinant alpha-cinnamomin: toxicity to cranberry and other plant species.
Elicitins produced by the pathogenic fungi Phytophthora are known to exhibit The elicitin cinnamomin is of nonspecific toxicity to different solanaceous plant species. particular interest for its potential role in the hypersensitive-like cell death and in the biological response of cranberry plants to the fungal pathogen Phytophthora cinnamomi. In order to understand the biochemical steps of the Phytophthora root rot disease in cranberry, we investigated the alpha-cinnamomin-induced plant responses. Toxicity of alpha-cinnamomin, which shows a high degree of sequence homology to the alpha-elicitin group, was tested on Vaccinum macrocarpon, Nicotiana tabacum, Capsicum annuum, Lycopersicon esculentum, Lactuca sativa, and Phaseolus vulgaris plants. Gene corresponding to alpha-cinnamomin gene fused with maltose binding protein gene, was cloned into a pMALTEV expression vector, which was transformed into E. coli cells. Cells containing alpha-cinnamomin clones were cultured and extracted protein was purified on a maltose binding protein affinity column. Biological activity of alpha-cinnamomin fusion protein was examined on propagated plants and cuttings. In cranberry plants treated with cinnamomin necrotic hypersensitive-like response in the proximal areas of the leaf lamina of lower plant leaves was observed after 48-72 hr of incubation. Limited leaf necrosis observed days after application of low amounts of recombinant cinnamomin directly on the leaves of other plants indicates that the recombinant protein might be functioning as a toxin, capable of inducing aging accompanied by plant cell death.


Whey protein inhibits iron overload-induced oxidative stress in rats.
In this study, we evaluated the effects of whey protein on oxidative stress in rats that were subjected to oxidative stress induced by iron overload. Thirty male rats were assigned to 3 groups: the control group (regular [50 mg/kg diet] dose of iron+20% casein), iron overload group (high [2,000 mg/kg] dose of iron+20% casein, IO), and whey protein group (high dose of iron+10% casein+10% whey protein, IO+whey). After 6 wk, the IO group showed a reduction in the plasma total radical trapping antioxidant parameter and the activity of erythrocyte superoxide dismutase and an increase in lipid peroxidation (determined from the proportion of conjugated dienes). However, whey protein ameliorated the oxidative changes induced by iron overload. The concentration of erythrocyte glutathione was significantly higher in the IO+whey group than in the IO group. In addition, whey protein supplementation fully inhibited iron overload-induced DNA damage in leukocytes and colonocytes. A highly significant positive correlation was observed between plasma iron levels and DNA damage in leukocytes and colonocytes. These results show the antioxidative and antigenotoxic effects of whey protein in an in vivo model of iron overload-induced oxidative stress.


Esthetic management of double tooth associated with talon cusp using a laminate veneer.
Double tooth and talon cusp are tooth shape anomalies with rare co-occurrences in a single tooth. Double tooth is a developmental anomaly that leads to the eruption of fused teeth and may contribute to compromised esthetics, pain, caries, and tooth crowding. Talon cusp is a rare developmental extra cusp-like projection on the cingulum area that may cause functional and esthetic problems. Differential diagnosis of these anomalies may be complicated. A multidisciplinary approach for the esthetic and functional rehabilitation of double teeth is important. Various treatment methods have been described in the literature for the different types and morphological variations of double teeth. The purpose of this paper is to report the case of an unusual combination of double tooth and talon cusp on a permanent maxillary incisor and describe its esthetic and functional rehabilitation using a porcelain laminate veneer.


Congenital neck masses.
Congenital neck lesions reflect abnormal embryogenesis in head and neck development. A thorough knowledge of embryology and anatomy is critical in the diagnosis and treatment of these lesions. The appropriate diagnosis of these lesions is necessary to provide appropriate treatment and long-term follow up, because some of these lesions may undergo malignant transformation or be harbingers of malignant disease.


Has the manufacturing policy helped to promote the logistics industry?
The logistics industry is a derivative industry of manufacturing services extraposition. A variety of strategies to develop the manufacturing industry are important programs of action for China's manufacturing strategic power, and it is of great significance to promote the high-quality development of the logistics industry. This paper takes strong manufacturing provinces with the development of the logistics industry as the research object and applies network DEA measuring the production efficiency and service efficiency of the logistics industry from 2004 to 2017. This paper adopts the "Made in China 2025" strategy as a natural experiment and uses double difference to study the impact of manufacturing policies on the high-quality development of the logistics industry. The empirical results show that compared with the Reference group, the impact of the "Made in China 2025" strategy led to a significant increase in the production efficiency and service efficiency of the experimental group. The group-based test based on innovation type shows that independent innovation has a significant positive effect on the high-quality development of the logistics industry, which shows that from the perspective of technological innovation, independent innovation is the main path of the "Made in China 2025" strategy to promote the high-quality development of the logistics industry. This paper not only identifies the causal relationship between the "Made in China 2025" strategy and the high-quality development of the logistics industry but also helps clarify the mechanism of how manufacturing policies improve the high-quality development of the logistics industry, which has important implications for further promoting the combined development between manufacturing and logistics.


Mixed-metal cluster chemistry. 29. Core expansion and ligand-driven metal exchange at group 6-iridium clusters.
Reactions of the tetrahedral clusters MoIr3(mu-CO)3(CO)8(eta-L) (L = C5HMe4, C5Me5) with the carbonylmetalate anions [Mo(CO)3(eta-L)]- afford the trigonal bipyramidal clusters Mo2Ir3(mu3-H)(mu-CO)2(CO)9(eta-L)2 (L = C5HMe4 (3c), 74%; L = C5Me5 (3d), 55%) in which the group 6 metal atoms occupy the apexes; reaction of the cyclopentadienylmolybdenum-containing analogues or their cyclopentadienyltungsten-containing homologues failed to afford analogous products. Reactions of MIr3(mu-CO)3(CO)8(eta-C5H5) (M = Mo, W) with [M(CO)3(eta-L)]- (L = C5HMe4, C5Me5) afford the core-expanded heteroapex clusters M2Ir3(mu3-H)(mu-CO)2(CO)9(eta-C5H5)(eta-L) (M = Mo, L = C5HMe4 (5c), 9%, L = C5Me5 (5d), 4%; M = W, L = C5Me5 (6d), 5%) in low yield, together with the homoapex clusters M2Ir3(mu3-H)(mu-CO)2(CO)9(eta-L)2 (M = Mo, L = C5HMe4 (3c), 81%, L = C5Me5 (3d), 60%; M = W, L = C5Me5 (4d), 5%) in much higher yield for the Mo-containing examples. The identities of clusters 3c,d, 4d, and 5c,d have been confirmed by single-crystal X-ray diffraction studies, with the same disposition of ligands about the trigonal bipyramidal cluster cores being observed in each case, a ligand arrangement that has been examined by complementary density functional theory studies. While cluster 5d is accessible as above, no reaction is observed from MoIr3(mu-CO)3(CO)8(eta-C5Me5) and [M(CO)3(eta-C5H5)]-. Treating MoIr3(mu-CO)3(CO)8(eta-C5H5) with 1 equiv of [M(CO)3(eta-C5Me5)]- affords 5d as the major product, a further 1 equiv affording some MoIr3(mu-CO)3(CO)8(eta-C5Me5) and a third 1 equiv giving a good yield of 3d. This is consistent with reaction proceeding by apex fragment addition, followed by apex fragment elimination, and finally a further apex fragment addition, the homometallic incoming apexes being distinguished from the departing vertices by their highly methylated cyclopentadienyl ligands. Spectroscopic data suggest that the electron density at these disparate-metal-containing cluster cores is tunable by progressive (conceptual) cyclopentadienyl alkylation.


[A clinical study of complements as a marker of a hepatocellular carcinoma].
Serum complement C3, C4, and C3 proactivator (C3PA) have been evaluated for their diagnostic power in detecting a hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). It was found that serum complement levels were lower in LC patients than in HCC patients and that difference of the serum C4 and C3PA levels between LC patients and HCC patients were statistically significant. In addition, serum C3 PA levels were found to correlate significantly with the serum gamma-GTP levels in HCC patients. Thus, using the cutoff values of C4 and C3PA as the mean values for HCC patients, examination of serum complement levels enabled the detection of 38% of the HCC patients with low AFP levels. These findings suggest that the examination of the serum complements may be a useful a tool for the detection of HCCs in LC patients.


Hierarchical Letters in ASD: High Stimulus Variability Under Different Attentional Modes.
Studies using hierarchical patterns to test global precedence and local-global interference in individuals with ASD have produced mixed results. The current study focused on stimulus variability and locational uncertainty, while using different attentional modes. Two groups of 44 children with and without ASD completed a divided attention task as well as a global and local selective attention task. The results revealed global-to-local and local-to-global interference in ASD, to the same extent as in the TD group. Both groups struggled with the same type of stimuli (i.e., ignoring the global level information) and performed similar in all three tasks. Future studies on (visual) information processing in ASD should pursue the impact of stimulus noise and trial-by-trial uncertainty further.


Influence of nicotine on monocyte phenotype and function.
Monocyte expression of class II antigens was studied in smokers and in nonsmokers using double marker analysis and flow cytometry. There was no difference in class II expression with 78.8% and 79.3% class II+ monocytes in smokers and nonsmokers, respectively. Further, in vitro treatment with nicotine at levels seen in smokers (50 ng/ml) did not alter class II expression either. When analyzing TNF production using the Wehi 164/ActD 51Cr-release assay we observed a two-fold lower TNF production in smokers versus nonsmokers. In vitro treatment of monocytes with nicotine, however, did not reduce the LPS triggered TNF production.


IQGAP1 silencing suppresses the malignant characteristics of laryngeal squamous cell carcinoma cells.
Laryngeal squamous cell carcinoma (LSCC) has a poor prognosis due to recurrence and metastasis. IQ-domain GTPase-activating protein 1 (IQGAP1), a scaffold protein, plays an important role in tumorigenesis and malignant development. In this study, we aimed to explore the role of IQGAP1 in LSCC. Expression of IQGAP1 in human LSCC specimens was assessed by immunohistochemistry. We also evaluated the roles of IQGAP1 in cell proliferation, migration and invasion and epithelial-to-mesenchymal transition (EMT) in Hep-2 cells. The expression of IQGAP1 protein was significantly up-regulated in LSCC tissues compared with normal laryngeal tissues (p = 0.002). Furthermore, the knockdown of IQGAP1 in Hep-2 cells inhibited cell growth, migration and invasion. Moreover, we found that IQGAP1 silencing reversed EMT. These results show for the first time that IQGAP1 is up-regulated in LSCC tissues and plays an important role in LSCC cell proliferation and invasiveness, which indicates that IQGAP1 could work as an oncogene and may serve as a promising molecular target for treatment of LSCC.


[The antiarrhythmic effects of verapamil in acute myocardial infarction. Considerations on the possible action mechanism (author's transl)].
In 12 patients affected by acute myocardial infarction complicated only by ventricular extrasystoles, verapamil was highly effective in the control of the arrhythmias. This result is in agreement with the experimental finding that ischemia inactivates partially or totally early Na+ inward currents, so that fast fibers become slow fibers. The efficacy of verapamil stresses the importance of these fibers which have acquired a slow response in the genesis of arrhythmias due to acute coronary attacks and opens interesting therapeutical prospects.


Functional properties of single neurons in the primate face primary somatosensory cortex. III. Modulation of responses to peripheral stimuli during trained orofacial motor behaviors.
1. In previous papers we have demonstrated that most single neurons in the face primary somatosensory cortex (SI) alter their firing rate during a trained tongue-protrusion task and some also during a trained biting task. Although the data suggest that some of the task-related activity in face SI might conceivably come from reafferent inputs from moving orofacial structures, it is possible that orofacial inputs are modulated during the trained orofacial movements. This study was initiated to investigate the possible modulation of evoked orofacial somatosensory responses of face SI neurons during trained tongue-protrusion and biting tasks. 2. Two monkeys were trained to perform a tongue-protrusion and a biting task and to accept stimulation applied to the facial skin or the lingual nerve during the tasks. For SI neurons with a tongue mechanoreceptive field (RF), electrical stimulation was applied to the lingual nerve to elicit neuronal activity; for SI neurons with a RF at the other locations, electrical or mechanical stimulation was applied to the RF to elicit neuronal activity. Modulation of neuronal activity evoked by low-threshold stimulation of the RF was tested, during the tongue-protrusion and/or biting tasks, in 44 face SI neurons and an additional 3 forelimb SI neurons with a palm RF (palm RF neurons). The 44 face SI neurons included 13 with a tongue RF (tongue RF neurons), 29 with a lip RF (lip RF neurons), and 2 with a lateral face RF (face RF neurons). 3. For face SI neurons tested during both force dynamic and holding phases of the task period, the evoked activity (i.e., the number of evoked spikes in 50 ms after the onset of stimulation) was decreased in at least one of the two phases for the majority (90%) of 31 neurons studied during the tongue-protrusion task and 61% of 23 studied during the biting task. The proportion of neurons modulated during the tongue-protrusion task was significantly higher than that during the biting task. For the 18 face SI tested during both tasks, a decrease in evoked activity occurred in 10 lip RF neurons for both tasks and in the remaining 5 lip RF and 3 tongue RF neurons for the tongue-protrusion task only. No neurons tested showed a clear facilitation of evoked activity during the task period of either task.(ABSTRACT TRUNCATED AT 400 WORDS)


Quality of life in patients with primary hyperparathyroidism.
The clinical picture of primary hyperparathyroidism (PHPT) has changed over the last three decades and many asymptomatic patients are now diagnosed through the unexpected finding of high serum calcium levels. However, though not yet considered as typical features of the disease and therefore not included in the guidelines for surgery, many data are available on neuropsycological manifestations and their impact on quality of life in asymptomatic patients. PHPT patients indeed show early experience nonspecific symptoms, such as weakness, depression, sleep disturbance, memory loss and anxiety. Although the underlining mechanisms have not been still identified, the prevalence of psychiatric and cognitive deficits has been investigated in many studies, as well as the possible association with quality of life and well-being improvement after surgery. This article aims to review the current knowledge on quality of life in PHPT patients before and after surgery and the possible clinical implications of these findings.


[Change in expression of vascular endothelial growth factor in serum and wound tissue of rats with electrical burns].
To observe the change in expression of vascular endothelial growth factor (VEGF) in serum and wound tissue of rats with electrical burn (EB), and to explore its regulation mechanism in the pathological changes of EB. Sixty-four SD rats were divided into normal control group (n = 8) and EB group (n = 56) according to the random number table. Eight rats in EB group were sacrificed at post injury hour (PIH) 6 and on post injury day (PID) 1, 3, 7, 14, 21, and 28, to collect wound muscle tissue and serum samples. Histopathological changes in wound tissue were observed with HE staining. The serum content of VEGF was determined with double-antibody sandwich enzyme-linked immunosorbent assay. The expression level of VEGF in wound tissue was determined with Western blotting. VEGF expression intensity in wound tissue was observed with immunohistochemical staining. The microvessel density (MVD) was calculated. The correlation between VEGF expression intensity and MVD was analyzed. Muscle tissue of calf and serum of the rats in normal control group without any treatment were collected for above-mentioned observations and determinations. Data were processed with one-way analysis of variance and Spearman hierarchy correlation analysis, and LSD-t test was applied for paired comparison. (1) In EB group, breakage of muscle fiber, heavy infiltration of inflammatory cells, and obvious tissue edema were observed at PIH 6 and on PID 1; new vessels were observed on PID 3; amount of granulation tissue and number of new vessels were found to be increased on PID 7. (2) In EB group, the serum level of VEGF was (43 ± 11) pg/mL at PIH 6, (44 ± 11) pg/mL on PID 1, and (74 ± 27) pg/mL on PID 14, which were all significantly higher than that in normal control group [(15 ± 9) pg/mL, with t values from 4.001 to 5.724, P values all below 0.01]. (3) The protein expression level of VEGF of wound tissue in EB group was higher than that in normal control group (0.21 ± 0.09) at each time point. The protein expression level of VEGF in EB group peaked on PID 7 (0.63 ± 0.13, t = 4.965, P < 0.05). (4) In EB group, strongly positive expression of VEGF was observed in inflammatory cells at early stage and in new vascular endothelial cells at late stage. (5) The expression intensity of VEGF was positively correlated with MVD in wound tissue on PID 3, 7, 14, 21, and 28 in EB group (r(s) = 0.834, P < 0.01). Different expression levels of VEGF were observed in serum and wound tissue of rats at various stages after EB, and they were closely correlated with different stages of fluid exudation and wound healing process after EB.


[Relationship between subjective cognition and observed life-style in nursing students].
Complex interactions between long-standing lifestyles and genetic factors are strongly involved in the pathologenesis of adult diseases or chronic degenerative diseases. We usually use a questionnaire to obtain life-style information from subjects in a health survey. However, the response to questionnaires is a subjective recognition, therefore, it does not always precisely correspond to the actual situation. The purpose of this research is to compare the response to the questionnaire about life-styles with facts that can be objectively observed. Furthermore, each aspect of life-styles was examined on a mutual influence grade. The subjects were ninety-eight nursing college students aged from 18 to 23 years old, in good health. Subjective symptoms and daily life practices were investigated by a 15-item questionnaire, as the first step. Therefore, we asked them to record their behavior on a time chart, everyday for ten days. Seven days of serial records were obtained from sixty-four subjects (65.3% of 98 persons). 1) The response "yes" to the questionnaire "Do you sleep well?" and "Do you fall asleep, easily?" was influenced by the hours of sleep, rather than what time the subjects "go-to-bed" or "get-up". The response to "Do you wake up often during the night?" expressed an actual situation, well. 2) For subjective cognition regarding excretion, the answer for "constipation" was associated with the number of defecation per week, though the answer for "diarrhea" was not. 3) The answer to "Do you eat breakfast?" reflected the actual situation. However, the answer for "Do you eat between meals?" did not express the actual situation, that is, even the subjects who answered "occasionally" or "I don't eat between meals" had eaten between meals 6.1 times per week, on average. 4) There were mutual influences among sleeping, eating breakfast and excretion.


Healthier vending machines in workplaces: both possible and effective.
To develop healthier vending guidelines and assess their effect on the nutrient content and sales of snack products sold through hospital vending machines, and on staff satisfaction. Nutrition guidelines for healthier vending machine products were developed and implemented in 14 snack vending machines at two hospital sites in Auckland, New Zealand. The guidelines comprised threshold criteria for energy, saturated fat, sugar, and sodium content of vended foods. Sales data were collected prior to introduction of the guidelines (March-May 2007), and again post-introduction (March-May 2008). A food composition database was used to assess impact of the intervention on nutrient content of purchases. A staff survey was also conducted pre- and post-intervention to assess acceptability. Pre-intervention, 16% of staff used vending machines once a week or more, with little change post-intervention (15%). The guidelines resulted in a substantial reduction in the amount of energy (-24%), total fat (-32%), saturated fat (-41%), and total sugars (-30%) per 100 g product sold. Sales volumes were not affected, and the proportion of staff satisfied with vending machine products increased. Implementation of nutrition guidelines in hospital vending machines led to substantial improvements in nutrient content of vending products sold. Wider implementation of these guidelines is recommended.


The soleal line: a cause of tibial pseudoperiostitis.
An unusually prominent soleal line (a normal anatomic variant) may mimic periosteal reaction along the posterior margin of the proximal tibial shaft. This area of pseudoperiostitis is differentiated from hyperostoses arising from the anterior tibial tubercle and the interosseous membrane. It is always associated with normal, undisturbed architecture of the underlying bone.


Does the habitat structure control the distribution and diversity of the Odonatofauna?
The statement that the habitat complexity and structure govern the abundance and diversity of biological communities has been widely investigated. In this context, we assumed the hypothesis of habitat heterogeneity, that is, the higher habitat complexity leads to greater diversity of Odonata. In addition, we analyzed the influence of habitat structure on the distribution of this community, and evaluated the effects of abiotic variables. Odonata larvae were collected with sieves and by electrofishing in ten neotropical streams belonging to the Pirapó River basin. Forty species of Odonata were registered, which were distributed in eight families, Libellulidae stood out with the highest richness. The high gamma diversity and distribution of Odonata were associated with habitat heterogeneity in these streams. However, the abiotic variables also seem to affect the distribution of Odonata species, in view of the impact of the land use in the vicinity of streams.


Direct player observation is needed to accurately quantify heading frequency in youth soccer.
In soccer, heading may be related to subsequent neurological impairment. Accurate measures of heading exposure are therefore important. This study evaluated whether 12 female youth players accurately recalled their average number of headers over an entire soccer season (20 games total). Their self-reported average number of headers per game was multiplied by the number of games that they participated in, and were compared to actual number of headers extracted from game video. All players overestimated the number of headers compared to game video. Linear regression analysis indicated that self-reported headers overestimated the number of headers by 51%. While self-reports are a convenient way to estimate heading behaviour, they do not accurately represent the number of headers that players perform. Self-reports of heading exposure should be interpreted with caution.


Early versus newer generation devices for transcatheter aortic valve implantation in routine clinical practice: a propensity score matched analysis.
Contemporary data comparing early versus newer generation transcatheter heart valve (THV) devices in routine clinical practice are lacking. We sought to compare the safety and efficacy of early versus newer generation THVs in unselected patients undergoing transcatheter aortic valve implantation (TAVI). We performed a propensity score matched analysis of patients undergoing transfemoral TAVI at a single centre with early versus newer generation devices between 2007 and 2016. Patients were matched for balloon-expandable versus self-expandable valves and Society of Thoracic Surgeons score. The primary end point was the Valve Academic Research Consortium (VARC)-2 early safety composite end point at 30 days. Among the 391 matched pairs, no differences between early (21.2%) and newer generation (20.8%) THVs regarding the early safety composite end point (HR 0.98, 95% CI 0.72 to 1.33, P=0.88) were observed. The rates of valve embolisation (0.8% vs 4.2%, P=0.005), bleeding events (24.8% vs 32.0%, P=0.028) and moderate-to-severe paravalvular regurgitation (PVR) (3.1% vs 12.1%, P<0.001) were lower among patients receiving newer generation devices. Conversely, patients treated with early generation THVs less frequently experienced annulus rupture (0% vs 2.0%, P=0.008). Newer compared with early generation THV devices were associated with a lower rate of valve embolisation, PVR and bleeding events.


[Are granulomas necessary for the final diagnosis of Crohn disease?].
A case of a 38 year-old male patient, from Lima, with a three-year period illness, characterized by abdominal pain, diarrhea, ponderal weight loss and fever is showed. He is examined by colonoscopy, with endoscopic diagnosis of colon cancer and undergoes surgery. The histopathological diagnosis was severe acute and chronic ulcerative ileocolitis, suggesting Crohn disease. A month later he again showed abdominal pain, diarrhea and fever, so a new colonoscopy is performed revealing multiple ileum ulcers and in the anastomotic area. The biopsy revealed an acute and chronic inflammatory process. The colon radiography showed a filling defect and irregularity in the cecum, and the upper endoscopy revealed esophageal ulcers. In addition, a number of analyses were carried out, such as: coproculture, HIV, and VK on sputum and feces, as well as CEA dosage, resulting all of them negative. The thorax radiography was also normal.He was diagnosed with Crohn's disease and was treated with mesalacin. Evolution was fast, showing weight gain, which allowed the discharge of the patient from the hospital seven (7) days later. The anatomical pathology never did confirm the final diagnosis, which brings us to the question:Are the granulomas always necessary for the final diagnosis of Crohn's disease?


Modulating the physicochemical and structural properties of gold-functionalized protein nanotubes through thiol surface modification.
Biomolecules are advantageous scaffolds for the synthesis and ordering of metallic nanoparticles. Rotavirus VP6 nanotubes possess intrinsic affinity to metal ions, a property that has been exploited to synthesize gold nanoparticles over them. The resulting nanobiomaterials have unique properties useful for novel applications. However, the formed nanobiomaterials lack of colloidal stability and flocculate, limiting their functionality. Here we demonstrate that it is possible to synthesize thiol-protected gold nanoparticles over VP6 nanotubes, which resulted in soluble nanobiomaterials. With this strategy, it was possible to modulate the size, colloidal stability, and surface plasmon resonance of the synthesized nanoparticles by controlling the content of the thiolated ligands. Two types of water-soluble ligands were tested, a small linear ligand, sodium 3-mercapto-1-propanesulfonate (MPS), and a bulky ligand, 5-mercaptopentyl β-D-glucopyranoside (GlcC5SH). The synthesized nanobiomaterials had a higher stability in suspension, as determined by Z-potential measurements. To the extent of our knowledge, this is the first time that a rational strategy is developed to modulate the particular properties of metal nanoparticles in situ synthesized over a protein bioscaffold through thiol coating, achieving a high spatial and structural organization of nanoparticles in a single integrative hybrid structure.


Revisiting the 1,2,4-triaza-3,5-diborolyl ligand: sigma and pi coordination modes in the alkali metal and rhodium complexes of a planar, 6-pi-electron B2N3- ring.
Lithium (2a), sodium (2b), and potassium (2c) salts of 1-methyl-3,5-diphenyl-4-methylamino-1,2,4-triaza-3,5-diborolyl were prepared by deprotonation of the ring nitrogen in neutral precursor 1. The alkali metal derivatives were characterized by multinuclear NMR, mass spectrometry, and single-crystal X-ray diffraction. The structural determinations revealed extended 2D structures for 2a and 2b and an extended 1D structure for 2c. All three solvent-free structures are dominated by sigma interactions, and pi interactions are also present for the potassium derivative. Addition of triphenylborane to 2a, 2b, and 2c produced the adducts 3a, 3b, and 3c, respectively, and these were characterized by multinuclear NMR and mass spectrometry. Structural determinations have been performed for the lithium and potassium salt, showing that Ph3B coordinates at the 2 position of the ring, whereas the alkali metal is coordinated by the pendant methylamino group. The lithium ion is additionally coordinated by three acetonitrile molecules in the monomeric structure of 3a, whereas the potassium ion is coordinated by three phenyl groups, forming the 1D polymeric structure of 3c. Reaction of 2a with [Rh(cod)Cl]2 yielded the dimeric 4, containing two 1,2,4-triaza-3,5-diborolyl rings bridging two Rh(cod) fragments through the substituent-free ring nitrogen atoms.


▼Asenapine for bipolar I disorder?
About 1 in 100 people has bipolar disorder (manic depression) at some point in their lives.(1) Associated mood swings of depression and mania can be both unpleasant and destructive.(2) It is advised to start medical treatment early, and traditionally this has involved the use of mood stabilisers, antipsychotics and antidepressants.(2) ▾Asenapine (Sycrest - Lundbeck) is a new sublingual antipsychotic drug, licensed for the treatment of moderate to severe manic episodes associated with bipolar I disorder in adults.(3) Here we review the evidence and practical implications associated with the use of this new medication.


Clinical Impact of Sagittal Spinopelvic Parameters on Disc Degeneration in Young Adults.
The sagittal balance plays an important role in the determination of shear and compressive forces applied on the anterior (vertebral bodies and intervertebral discs) and posterior (facet joints) elements of the lumbar vertebral column. Many studies have also examined the effect of structural changes in the disc on the biomechanical characteristics of the spinal segment. Nevertheless, the relationship between sagittal balance and the degree of disc degeneration has not been extensively explored. Thus, here we investigated the relationships between various sagittal spinopelvic parameters and the degree of disc degeneration in young adults.A total of 278 young adult male patients were included in this study (age range: 18-24 years old). Multiple sagittal spinopelvic parameters, including pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), sacral inclination (SI), lumbosacral angle (LSA), and sacral table angle (STA), were measured from standing lateral lumbosacral radiographs. The degree of intervertebral disc degeneration was classified using a modified Pfirrmann scale. To assess the pain intensity of each patient, the visual analogue scale (VAS) score for low back pain (LBP) was obtained from all the patients. Finally, the relationships between these spinopelvic parameters and the degree of disc degeneration in young adults were analyzed. Also, we performed multiple logistic regression study.Out of all the spinopelvic parameters measured in this study, a low STA and a low SI were the only significant risk factors that were associated with disc degeneration in young adults. It means that patients with disc degeneration tend to have more severe sacral kyphosis and vertical sacrum.We found that patients with disc degeneration showed a lower SI and lower STA compared with patients without disc degeneration in young adults. Therefore, we suggest that the patients with disc degeneration tend to have more vertical sacrum, more sacral kyphosis, and more severe LBP, and that SI and STA measurements should be carefully considered to predict or prevent further disc degeneration and LBP.


Determine phenotypical patterns of resistance to antibiotics in COVID-19 patients with associated bacterial infection: largest medical center in Iran.
Antibacterial resistance (AMR) is a serious threat and major concern, especially in developing countries. Therefore, we aimed to determine phenotypical patterns of resistance to antibiotics in COVID-19 patients with associated bacterial infection in intensive care units. In this cross-sectional study, 6524 COVID-19 patients admitted for more than 48 h in the ICUs of Imam Khomeini Complex Hospital (IKCH) in Tehran from March 2020 to January 2022 were included in the study with initial diagnosis of COVID-19 (PCR test and chest imaging). Data were collected regarding severity of the illness, primary reason for ICU admission, presence of risk factors, presence of infection, length of ICU and hospital stay, microbial type, and antibiotic resistance. In this study, the pattern of antibiotic resistance was determined using the Kirby-Bauer disk diffusion method. In this study, 439 (37.5%) were ventilator-related events (VAEs), and 46% of all hospitalized patients had an underlying disease. The most common microorganisms in COVID-19 patients were carbapenem resistant Klebsiella pneumoniae (KPCs) (31.6%), Escherichia coli (E. coli) (15.8%), and Acinetobacter baumannii (A. baumannii) (15.7%), respectively. Prevalence of vancomycin-resistant enterococci (VRE) and KPCs were 88% and 82%, respectively. A study on AMR surveillance is the need of the hour as it will help centers to generate local antibiograms that will further help formulate national data. It will guide doctors to choose the appropriate empiric treatment, and these studies will be the basis for establishing antimicrobial surveillance and monitoring and regulating of the use of antimicrobials.


Stimulation of partially purified adenylate cyclase from bull sperm by bicarbonate.
Solubilized and partially purified adenylate cyclase from bull sperm was found to be specifically activated (up to 6-fold) by sodium bicarbonate (NaHCO3) and to a lesser extent by NaNO3. Other sodium salts were either ineffective (e.g. NaCOOH) or inhibitory (e.g. NaHSO3, NaHSO4 and Na2B4O7). Stimulation by NaHCO3 was dose-dependent in the range of 0-40 mM and was greater when enzyme activity was assayed in the presence of magnesium as compared with manganese ions. Bicarbonate seems to affect maximal enzyme velocity (Vmax) and has no effect on the Km of adenylate cyclase for Mn-ATP. Stimulation of adenylate cyclase by NaHCO3 coincided with the elution pattern of the enzyme as recorded following chromatography on DEAE-cellulose or gel filtration on BioGel P-100. These results suggest that in the course of stimulation of sperm adenylate cyclase, bicarbonate is likely to interact directly with the enzyme. Furthermore, this intrinsic and unique property of sperm adenylate cyclase may explain results reported by others on the stimulation of cAMP production by bicarbonate in intact and broken sperm preparations and suggest a biochemical basis for enhanced sperm motility associated with high bicarbonate concentrations.


The relationship between maternal risk status and maternal sensitivity.
The relationship between parental risk condition and parents' sensitivity to infants' cues was measured in one father-infant and 59 mother-infant dyads. Parents were videotaped at home, playing with their infants. Systematic differences in interactional patterns were found across six parental risk groups--neglectful, abusing, mentally retarded, low-income, deaf, and middle class (non-risk) parents. Sources of differences are discussed and implications for intervention strategies are offered.


Philip John DiSaia, MD: Available Light & The Origin of Storms.
During a career, which spanned nearly 60 years, Professor Philip J. DiSaia (1937-2018) trailblazed a path forward in academic medicine, which would become the standard by which Departments of Obstetrics and Gynecology and Gynecologic Oncology Divisions and Cancer Centers would be measured throughout the United States, in Europe and Japan. Following his discovery of fetal warfarin syndrome as a resident, DiSaia would serve in the U.S. Navy and successfully compete for an American Cancer Society Grant that would fund his Fellowship in Gynecologic Oncology under the instruction of Dr Felix N. Rutledge at the MD Anderson Hospital and Tumor Institute in Houston, Texas. Dr DiSaia's goal to establish a traditional academic department was realized at the University of California, Irvine, where he remained active in an unprecedented, uninterrupted 42-year run, training many outstanding obstetrician-gynecologists and gynecologic oncologists, future Division Directors, Cancer Center Directors and Department Chairpersons. His dedication to the field and inexhaustible work ethic fueled his many successes in tumor immunology and the clinical trials of the National Cancer Institute's Gynecologic Oncology Group.


An exceptional evolution of primary peritoneal serous carcinoma.
Primary peritoneal serous carcinoma (PPSC) is a rare malignancy of the peritoneum. Clinically and histopathologically, PPSC is similar to serous ovarian papillary carcinoma. Brain metastases (BM) from PPSC are exceedingly rare. We report here a new case of BM two years after complete remission from a PPSC, to make aware physicians about this entity. This case is exceptional; firstly given the rarity of this entity and secondly due to the good response after radiotherapy then systemic chemotherapy with Carboplatin and Paclitaxel.


Synthesis and antitumor properties of an anthraquinone bisubstituted by the copper chelating peptide Gly-Gly-L-His.
A new molecule 4 [(GGH-DAE)2DHQ] associating the 1,4,5,8-tetrahydroxyanthraquinone ring (DHQ) of the antitumor drug mitoxantrone (2), two diaminoethylene chains (DAE), and the metal-chelating peptide Gly-Gly-His (GGH) has been synthesized. Such a molecule presents characteristics able to induce antitumor activity: compound 4 intercalates into DNA as measured by delta Tm, fluorescence quenching, and viscometry; ESR studies demonstrate that several types of Cu complexes are formed depending on pH; and the production of free radicals, as evidenced by spin-trapping, is enhanced by 4. In vitro, in leukemia cells L1210 and mammary cells MCF7, 4 is slightly less cytostatic than mitoxantrone, but substantially less toxic. In vivo, in leukemia P388 on mice, a T/C value of 230 is obtained at 25 mg/kg, higher than the one of mitoxantrone, which is toxic at the same dose.