Designer Outer Membrane Protein Facilitates Uptake of Decoy Molecules into a Cytochrome P450BM3-Based Whole-Cell Biocatalyst.
We report an OmpF loop deletion mutant, which improves the cellular uptake of external additives into an Escherichia coli whole-cell biocatalyst. Through co-expression of the OmpF mutant with wild-type P450BM3 in the presence of decoy molecules, the yield of the whole-cell biotransformation of benzene could be considerably improved. Notably, with the decoy molecule C7AM-Pip-Phe the yield duodecupled from 5.7 % to 70 %, with 80 % phenol selectivity. The benzylic hydroxylation of alkyl- and cycloalkylbenzenes was also examined, and with the aid of decoy molecules, propylbenzene and tetralin were converted to 1-hydroxylated products with 78 % yield and 94 % (R) ee for propylbenzene and 92 % yield and 94 % (S) ee for tetralin. Our results suggest that both the decoy molecule and substrate traverse the artificial OmpF channel, synergistically boosting whole-cell bioconversions.


Eye and Orbital Injuries in Sports.
Sports-related eye and orbital injuries continue to occur regularly and may have serious consequences. They are completely preventable when appropriate protection is worn, particularly with polycarbonate lenses. Eye protection is available for most sports and should be worn in accordance with the standards of regional authorities. It is important for first responders to identify red flags in the history and physical examination of an injured athlete for urgent referral to an ophthalmologist. Common sports-related eye injuries include corneal abrasion, subconjunctival hemorrhage, hyphema, vitreous hemorrhage, retinal tears and detachment. The mechanism and treatment of these injuries are discussed in further detail.


The 28k and 70k dalton polypeptide components of mouse Ra-reactive factor are responsible for bactericidal activity.
Ra-reactive factor is a complement-dependent bactericidal factor that reacts specifically with Ra chemotype strains of Salmonella, and is ubiquitous in sera of a wide variety of vertebrates. Here we prepared an antiserum by immunizing rabbit with mouse Ra-reactive factor. This serum neutralized markedly the bactericidal activity of the factor. This action of the antiserum was inhibited by the factor whose bactericidal activity has been inactivated by heating for 30 min at 55 degrees C. Component polypeptides with apparent molecular weights of 28k and 70k in the factor were separated by SDS-polyacrylamide gel electrophoresis. They were also found to inhibit the antiserum activity. This indicates that these polypeptides carry the active site of the factor.


Anxiogenic-like effects of mCPP and TFMPP in animal models are opposed by 5-HT1C receptor antagonists.
1-(3-chlorophenyl)piperazine (mCPP) and 1-[3-(trifluoromethyl)phenyl]piperazine (TFMPP) (0.1-1.0 mg/kg) reduce total interaction time in a rat social interaction test under low light familiar conditions and its following components; grooming, following, crawling over, fighting, sniffing. Locomotion was only reduced by the highest dose of mCPP. mCPP also reduced activity in the light but not total locomotion in a light/dark transition test. These results suggest that mCPP (and TFMPP) are anxiogenic but not sedative in these tests. The effect of mCPP on social interaction was blocked by three antagonists which share a high affinity for 5-HT1C and 5-HT2 receptors: mianserin, cyproheptadine and metergoline but not by the 5-HT2 antagonists ketanserin or ritanserin or the 5-HT1A and 5-HT1B antagonists cyanopindolol and (-)-propranolol. It was prevented by a low (0.05 mg/kg) but not by a high (1.0 mg/kg) dose of ICS 205,930 a specific 5-HT3 antagonist reported to be anxiolytic at low doses. It was also prevented by chronic pretreatment with the anxiolytic drug chlordiazepoxide. These results argue for an anxiogenic action of mCPP mediated by 5-HT1C receptors. Since the chronic chlordiazepoxide pretreatment did not prevent the hypolocomotion or hypophagia induced by mCPP at high dosage (5 mg/kg) these latter effects are unlikely to be secondary to anxiety.


Detection of haemosporidian parasites in wild and domestic birds in northern and central provinces of Iran: Introduction of new lineages and hosts.
Haemosporidian parasites characterize multi-host and multi-parasite structures which are prevalent among wild bird populations. Here, determination of host records, estimation of the prevalence and diversity of haemosporidian lineages were performed in wild and domestic birds in 11 provinces in Iran. To our knowledge, for the first time in this region, molecular characterization of haemosporidians in migratory water birds, raptors, and domestic birds was carried out: blood or tissue samples were collected from 246 birds belonging to 36 species, 12 families, and 11 orders. The prevalence of Plasmodium, Haemoproteus, and Leucocytozoon were documented as 1.21%, 3.65%, and 0.4%, respectively. Of 36 birds' species inspected in this investigation, 13 individuals of 9 species were parasitized by blood parasites. To our knowledge, five lineages including hANACRE03, hAYTFER01, hAYTFER02, hAQUCYR01, and hSTAL06 were found as un-described lineages, while six known lineages of hLK03, pLK05, lTUSW04, pSW5, hMILANS02, and hHAECOL1 were recorded in hosts within novel geographical regions. Such results are required to fill the gaps in understanding the geographical distribution patterns of wildlife related vector-borne parasites in migratory birds as potential carriers, raptors with high vulnerability, and domestic birds as pet or with economic value.


Subcortical pathways serving cortical language sites: initial experience with diffusion tensor imaging fiber tracking combined with intraoperative language mapping.
The combination of mapping functional cortical neurons by intraoperative cortical stimulation and axonal architecture by diffusion tensor MRI fiber tracking can be used to delineate the pathways between functional regions. In this study the authors investigated the feasibility of combining these techniques to yield connectivity associated with motor speech and naming. Diffusion tensor MRI fiber tracking provides maps of axonal bundles and was combined with intraoperative mapping of eloquent cortex for a patient undergoing brain tumor surgery. Tracks from eight stimulated sites in the inferior frontal cortex including mouth motor, speech arrest, and anomia were generated from the diffusion tensor MRI data. The regions connected by the fiber tracking were compared to foci from previous functional imaging reports on language tasks. Connections were found between speech arrest, mouth motor, and anomia sites and the SMA proper and cerebral peduncle. The speech arrest and a mouth motor site were also seen to connect to the putamen via the external capsule. This is the first demonstration of delineation of subcortical pathways using diffusion tensor MRI fiber tracking with intraoperative cortical stimulation. The combined techniques may provide improved preservation of eloquent regions during neurological surgery, and may provide access to direct connectivity information between functional regions of the brain.


Inhibitor-bound complexes of dihydrofolate reductase-thymidylate synthase from Babesia bovis.
Babesiosis is a tick-borne disease caused by eukaryotic Babesia parasites which are morphologically similar to Plasmodium falciparum, the causative agent of malaria in humans. Like Plasmodium, different species of Babesia are tuned to infect different mammalian hosts, including rats, dogs, horses and cattle. Most species of Plasmodium and Babesia possess an essential bifunctional enzyme for nucleotide synthesis and folate metabolism: dihydrofolate reductase-thymidylate synthase. Although thymidylate synthase is highly conserved across organisms, the bifunctional form of this enzyme is relatively uncommon in nature. The structural characterization of dihydrofolate reductase-thymidylate synthase in Babesia bovis, the causative agent of babesiosis in livestock cattle, is reported here. The apo state is compared with structures that contain dUMP, NADP and two different antifolate inhibitors: pemetrexed and raltitrexed. The complexes reveal modes of binding similar to that seen in drug-resistant malaria strains and point to the utility of applying structural studies with proven cancer chemotherapies towards infectious disease research.


Nonviral Gene Therapy of the Nervous System: Electroporation.
Electroporation has been widely used to efficiently transfer foreign genes into the mammalian central nervous system (CNS), and thus plays an important role in gene therapeutic studies on some brain disorders. A lot of work concerning electroporation is focused on gene transfer into rodent brains. This technique involves an injection of nucleic acids into the brain ventricle or specific area and then applying appropriate electrical field to the injected area. Here, we briefly introduced the advantages and the basic procedures of gene transfer into the rodent brain using electroporation. Better understanding of electroporation in rodent brain may further facilitate gene therapeutic studies on brain disorders.


Stiffness measurement of the neocallus with the Fraktometer FM 100.
The assessment of fracture healing is subjective, and neither radiology nor manual examination allows a reliable determination of bone healing. Fracture healing control in the treatment of tibia shaft fracture with external fixator by a stiffness measurement system (Fraktometer FM 100) is known from clinical studies. The purpose of this study was to follow stiffness control at external fixator in healing of callotasis with the stiffness measurement system. From 1994 to 1997 stiffness measurements with the described system (Fraktometer FM 100) were performed in the BG-Clinic Ludwigshafen to assess the healing course in 11 cases of callotasis at lower limb. In ten cases, regular healing could be followed by signal decrease; in one case, a persistent signal without tendency to decrease was able to reveal callotasis failure at an early point of time. The investigation could also show the importance of bending stiffness control. One case of late axis deformation after fixator removal occurred because of disregarding delayed bending signal decrease. Measurements of the external fixator's stiffness after callotasis can provide useful additional information for further treatment strategy.


A rare case of aortocoronary dissection following percutaneous transluminal coronary angioplasty: successful treatment using off-pump coronary artery bypass grafting.
Retrograde dissection of the aorta is a rare but potentially life threatening complication of percutaneous coronary intervention. We describe a case of retrograde aortic dissection, which occurred during attempted percutaneous transluminal coroanary angioplasty (PTCA) of chronically occluded left anterior descending artery (LAD). Emergency coronary artery bypass grafting (CABG) was performed to revascularise LAD distal to the site of entry tear with pedicled left internal mammary artery (LIMA). This was achieved off-pump. Ascending aorta was not replaced as the dissection was localised.


Childhood maltreatment profile in a clinical population in China: a further analysis with existing data of an epidemiologic survey.
To determine the lifetime prevalence and diverse profiles of types of childhood maltreatment (CM) in a high-risk clinical sample using standardized assessment tools (Child Trauma Questionnaire, CTQ) in China, Shanghai, 2090 subjects were sampled from the Shanghai Mental Health Centre. Personality disorder (PD) was assessed using the Personality Diagnostic Questionnaire (PDQ-4+) and subjects were interviewed using the Structured Clinical Interview (SCID-II). CTQ was used to assess CM in five domains (emotional abuse, EA; physical abuse, PA; sexual abuse, SA; emotional neglect, EN; and physical neglect, PN). The prevalence estimate of EA in the sample is 22.2%, followed by 17.8% of PA, and 12.5% of SA. The prevalence estimate was more frequent in PN (65.0%) and in EN (34.0%) than in childhood abuse (EA, PA and SA). It seems that males reported more PA and females reported more SA, the older subjects reported more neglect and the younger subjects reported more abuse. There was a higher prevalence of EA and SA in borderline PD patients (44.4%, 22.5%), PA in antisocial PD patients (38.9%). Multi-PD patients reported more forms of CM in childhood. Additionally, factor analysis of CTQ items confirmed factorial validity by identifying a five-factor structure that explained 50% of the total variance. These findings support the view that prevalence of CM was commonly experienced in clinical population during their childhood, especially for subjects with PDs. Factorial validity in PN needs to be further improved, and can in part be culturally explained.


Update on treatments of psychological nonepileptic seizures.
The literature on treatment of psychological nonepileptic seizures (NES) is limited, marked by a number of case reports and anecdotal approaches to this difficult-to-treat population. A recent review of the NES treatment literature revealed 20 reports dealing with NES treatment. The majority of the reports were class IV studies. Since the prior review, a number of pilot trials in NES treatment have been published. In this article, we summarize the etiologic conceptualizations of NES, and link these to mechanism informed treatments. We describe the recent literature on NES treatments and propose future directions for intervention research.


Custom CAD/CAM implants for complex craniofacial reconstruction in children: Our experience based on 136 cases✰.
CAD-CAM patient-specific implants offer cerebral protection and improved facial balance without the disadvantages of autologous bone grafting such as donor site morbidity and unpredictable resorption. Several alloplastic materials are available, but titanium, polymethylmethacrylate (PMMA), and polyetheretherketone (PEEK) are the current popular choices. We reviewed our experience of applying different alloplastic CAD-CAM materials in the reconstruction of complex pediatric craniofacial deformities. A retrospective review was performed of all pediatric patients who underwent a complex inlay or onlay implant craniofacial reconstruction using CAD-CAM PEEK, PMMA, or titanium implants at a single institution. Demographics, cost, operative time, complications, and outcomes were assessed. Between 2003 and 2014, 136 patients (69 male; 67 female; mean age 11.5 years (3-22 years); mean follow-up 30 months) had custom patient-specific craniofacial reconstruction with PEEK (n = 72), PMMA (n = 42), and titanium (n = 22) implants (inlay = 93; onlay = 43). Indications included congenital anomalies (26.5%), decompressive craniectomies (25.0%), craniofacial syndromes (25.7%), tumor defects (14.0%), and post-trauma (6.6%). Implant cost varied significantly for PEEK ($7703 CAD) and PMMA ($8328 CAD) compared with that for titanium ($11,980 CAD) (p < 0.0005). Six patients (4.4%) required surgery due to infection consisting of irrigation and antibiotic administration with successful implant salvage in three patients. All infections occurred in the PEEK group. Five patients (3.7%) ultimately had implants removed due to infection (n = 3), late exposure (titanium; n = 1), or late fracture (PMMA; n = 1). CAD-CAM alloplast reconstruction in the management of complex pediatric craniofacial deformities is effective although expensive. Implant infection does not always require explantation. A reconstruction algorithm is presented.


Developmental pharmacology and toxicology: principles of study design and problems of methodology.
Pharmacologic investigations in the fetus, neonate and child are difficult for the various reasons outlined above, ranging from ethical constraints to difficulties with microanalytic techniques. Attempts to circumvent these difficulties through animal studies, retrospective analyses, and prospective surveys have provided only partial answers. These studies have often helped to guide subsequent similar studies in humans. Results of developmental pharmacologic studies applied to the human must be conducted in humans. The alternatives to randomized, controlled trials presented above may help with these studies, but these innovative study designs must be applied carefully to avoid biasing the results. Although difficult, definitive studies in developmental pharmacology are possible with investigators willing to work within the ethical constraints outlined above, to sensitively consider the needs of perinatal and pediatric patients, and to adhere to the strictest standards of study design.


Exploring determinants and regional variation of diagnostic imaging utilization rates in German inpatient care.
Germany ranks high concerning the per capita supply of computer tomographs (CT) and positron emission tomographs (PET) which may incentivize supply-induced use. Beyond that, international comparison shows high per capita examinations. However, misuse of diagnostic imaging may cause harm to patients and the health care system. The use of diagnostic imaging in Germany has been insufficiently studied so far. Therefore, the study aimed to determine the extent of regional differences as well as supply and demand side factors of per capita CT and PET examinations in German inpatient care. Cartographic visualizations and a random intercept model controlling for the regional disease burden, ambulatory provided supply and demand, and population deprivation between 2010 and 2017 for CT and between 2016 and 2017 for PET were applied. For this purpose, the Nationwide hospital discharge data (DRG statistics), hospital structured quality reports, the National Association of Statutory Health Insurance Physicians, the Central Research Institute of Ambulatory Health Care in Germany, and the German Index of Socioeconomic Deprivation were used. We found a substantial regional variation of examination rates (-63 to +108% for CT and from -94 up to +847% for PET). Regarding PET, the supply structures have a significant impact on examinations per 1,000 inhabitants (28.46, p < .000). Both devices were used in correlation with the regional disease burden. Ambulatory and inpatient CT examination rates were positively associated. The regional differences identified are to some extent attributable to the regional burden of disease and thus warranted. Although the inpatient PET supply influences utilization rates, the direction of the effect should be investigated more closely for valid statements. The findings in terms of CT should be treated with caution. The cartographic distribution and examination rates indicate global overuse. The clear separation of inpatient and ambulatory sectors leads to misallocation of scarce resources, medically unnecessary multiple examinations, and capacity utilization problems. The results obtained have great potential for assessing and analyzing the adoption and rapid expansion of imaging technologies. Capacity utilization figures should be the focus of further research to assess utilization rates both economically and medically. Policy makers should address ongoing issues of operational and organizational separation of inpatient and ambulatory sectors in the German health care system.


[Surgical treatment of burns : Special aspects of pediatric burns].
Treatment of pediatric burn patients is very important because of the sheer frequency of burn wounds and the possible long-term ramifications. Extensive burns need special care and are treated in specialized burn centers. The goal of this work is to present current standards in burn therapy and important innovations in the treatment of burns in children so that the common and small area burn wounds and scalds in pediatric patients in day-to-day dermatological practice can be adequately treated. Analysis of current literature, discussion of reviews, incorporation of current guidelines. Burns in pediatric patients are common. Improvement of survival can be achieved by treatment in burn centers. The assessment of burn depth and area is an important factor for proper treatment. We give an overview for outpatient treatment of partial thickness burns. New methods may result in better long-term outcome. Adequate treatment of burn injuries considering current literature and guidelines improves patient outcome. Rational implementation of new methods is recommended.


The Trajectory of Dyspnea in Hospitalized Patients.
The trajectory of dyspnea for patients hospitalized with acute cardiopulmonary disease, who are not terminally ill, is poorly characterized. To investigate the natural history of dyspnea during hospitalization and examine the role that admission diagnosis, and patient factors play in altering symptom resolution. Prospective cohort study of patients hospitalized for an acute cardiopulmonary condition at a large tertiary care center. Dyspnea levels and change in dyspnea score were the main outcomes of interest and were assessed at admission, 24 and 48 hours, and at discharge using the verbal 0-10 numeric scale. Among 295 patients enrolled, the median age was 68 years, and the most common admitting diagnoses were heart failure (32%), chronic obstructive pulmonary disease (COPD) (39%), and pneumonia (13%). The median dyspnea score at admission was 9 (interquartile range [IQR] 7-10); decreased to 4 (IQR 2-7) within the first 24 hours; and subsequently plateaued at 48 hours. At discharge, the median score had decreased to 2.75 (IQR 1-4). Compared to patients with heart failure, patients with COPD had higher median dyspnea score at baseline and admission and experienced a slower resolution of dyspnea symptoms. After adjusting for patient characteristics, the change in dyspnea score from admission to discharge was not significantly different between patients hospitalized with congestive heart failure, COPD, or pneumonia. Most patients admitted with acute cardiopulmonary conditions have severe dyspnea on presentation, and their symptoms improve rapidly after admission. The trajectory of dyspnea is associated with the underlying disease process. These findings may help set expectations for the resolution of dyspnea symptoms in hospitalized patients with acute cardiopulmonary diseases.


The Mechanism Underlying Change in the Sex Gap in Life Expectancy at Birth: An Extended Decomposition.
The relationship between differential mortality rates and differences in life expectancy is well understood, but how changing differential rates translate into changing differences in life expectancy has not been fully explained. To elucidate the mechanism involved, this study extends existing decomposition methods. The extended method decomposes change in the sex gap in life expectancy at birth into three components capturing the effects of the sex difference in mortality improvement (ρ-effect), life table deaths density by age (f-effect), and remaining life expectancy by age (e-effect). These three effects oppose and augment each other, depending on relative change in sex-differential mortality rates. The new method is applied to period data for 35 countries and cohort data for 25 countries. The results demonstrate how the mechanism, involving the three effects, operates to determine change in the sex difference in life expectancy. We observe the pivotal importance of the f-effect, which is predominantly negative because of lower female mortality, in favoring narrowing rather than widening of the sex gap, in shifting the overall effect to younger ages, and in exaggerating fluctuations due to crisis mortality. The new decomposition provides a more detailed basis for substantive analyses examining change in differences in life expectancy.


Applications for Electrical Impedance Tomography (EIT) and Electrical Properties of the Human Body.
Electrical Impedance Tomography (EIT) is a promising application that displays changes in conductivity within a body. The basic principle of the method is the repeated measurement of surface voltages of a body, which are a result of rolling injection of known and small-volume sinusoidal AC current to the body through the electrodes attached to its surface. This method finds application in biomedicine, biology and geology. The objective of this paper is to present the applications of Electrical Impedance Tomography, along with the method's capabilities and limitations due to the electrical properties of the human body. For this purpose, investigation of existing literature has been conducted, using electronic databases, PubMed, Google Scholar and IEEE Xplore. In addition, there was a secondary research phase, using paper citations found during the first research phase. It should be noted that Electrical Impedance Tomography finds use in a plethora of medical applications, as the different tissues of the body have different conductivities and dielectric constants. Main applications of EIT include imaging of lung function, diagnosis of pulmonary embolism, detection of tumors in the chest area and diagnosis and distinction of ischemic and hemorrhagic stroke. EIT advantages include portability, low cost and safety, which the method provide, since it is a noninvasive imaging method that does not cause damage to the body. The main disadvantage of the method, which blocks its wider spread, appears in the image composition from the voltage measurements, which are conducted by electrodes placed on the periphery of the body, because the injected currents are affected nonlinearly by the general distribution of the electrical properties of the body. Furthermore, the complex impedance of the skin-electrode interface can be modelled by using a capacitor and two resistor, as a result of skin properties. In conclusion, Electrical Impedance Tomography is a promising method for the development of noninvasive diagnostic medicine, since it is able to provide imaging of the interior of the human body in real time without causing harm or putting the human body in risk.


Neuropathy presenting as prolonged dyspnea. Case report and review of literature.
Polyneuropathy presented as isolated respiratory muscular paralysis. Transdiaphragmatic pressure measurements, nerve conduction studies, electromyography, and biopsy of intercostal muscle confirmed the nature of the process. Patients with unexplained respiratory insufficiency must be carefully evaulated for underlying neuromuscular disease.


Voice onset time of alveolar stop /t/ and realization of unaspirated affricates associated with Mandarin-speaking children with repaired cleft palate.
To examine perceptually the realization of unaspirated affricates and voice onset time (VOT) features of /t/ in Mandarin-speaking children with repaired cleft palate, and to explore the difficulties associated with unaspirated affricate production from the perspective of the VOT of /t/. Twenty-three children with repaired cleft palate and 22 age-matched typical native Mandarin speakers were recruited. Speakers with cleft palate were allocated into two groups based on expert perceptual judgment of nasality: one group with perceived normal resonance (PNR) (n = 14, average age = 9.3 years), and another group with perceived hypernasal resonance (PHR) (n = 9, average age = 10.3 years). Stimuli were collected through a series of picture naming tasks, targeting the production of initial consonants /t/ and three unaspirated Mandarin affricates /ts, tʂ, tɕ/. The productions of each affricate were evaluated by two experienced speech therapists. The VOT of /t/ was measured using PRAAT speech analysis software. The majority of unaspirated affricates were omitted and/or weakly realized by the group of PHR speakers, but not for the PNR group. A significantly smaller mean VOT value associated with /t/ was identified for the PHR group, as compared to the PNR group. A group difference for VOT value was not found between the PNR group and the typical control group. The voicing features of /t/ and omitted/weak realization of unaspirated affricates identified in the PHR group indicated that the deviant production of unaspirated affricates in the cleft palate group could be associated with the voicing characteristics of the alveolar stop /t/, and this merits further investigation.


Central venous access: techniques and indications in oncology.
Long lines can be inserted centrally or peripherally through patent veins into the central venous system down to the atrial caval junction. Traditionally surgeons, anesthetists, cardiologists and more recently interventional radiologists have been placing them using vein cutdown or percutaneous needle puncture techniques. Typical candidates for implanted venous catheters are cancer patients undergoing long-term chemotherapy. The most important issues, in addition to the patency of central veins and the history of previous indwelling catheters, pacewires or venous thrombosis, are the patient's performance status, body mass index, medical history and respiratory status, and the relevant technique. The present article will give an overview of the radiological and surgical implantation techniques and will highlight the impact of imaging means on the technical feasibility, assessment and treatment of device-related complications.


Microbial fatty acid specificity.
Strains ofRhodotorula sp.,Candida spp. andLangermania sp. cultivated on polyunsaturated oil preferentially incorporated more unsaturated fatty acids. These fatty acids were used mainly for growth needs whereas the saturated ones accumulated in the microbial cell. The cellular oil and the remaining oil in the culture had a lower degree of unsaturation as compared to the initial oil, and a modified fatty acid composition.Candida lipolytica, in a chemostat continuous culture, incorporated C(18) fatty acids in the order of C(18:3)>C(18:2)>C(18:1)>C(18:0), and accumulated mostly the saturated ones. The specific productivity of the cellular oil and of the oil remaining in the culture medium was 0.036 and 0.487 gg(-1) h(-1), respectively, at dilution rateD=0.2/h.


The effect of intravenous ritodrine on the acid-base status of the fetus during the second stage of labour.
A progressive fetal respiratory acidosis occurs in the second stage of labour. A double-blind controlled trial showed that the intravenous infusion of Ritodrine abolished this.


[Obsessive-compulsive disorders: how to recognize and treat them].
Obsessive-compulsive disorders are characterized by recurrent and persistent obsessive thoughts that are experienced as obtrusive and inappropriate, and (often stereotypic and repetitive) compulsive actions. Their lifetime prevalence is estimated to be 1-2%. Men and women are affected by such disorders in about equal numbers. The most common comorbidities are depression and anxiety. The etiology is considered to encompass both psychological and neurobiological aspects. The most effective therapeutic approach is cognitive behavioral therapy with exposure and response prevention as the central element, which leads to a lasting improvement in symptoms in some 60-80% of the patients. If a depressive disorder is also present, or if obsessive thoughts are predominant, a combination of cognitive behavioral therapy and pharmacological treatment with (selective) serotonin reuptake inhibitors has proven effective.


Aberrant Toxocara canis in a red fox.
During necropsy of a red fox (Vulpes vulpes) heart an adult, male Toxocara canis was found under the pericardium at the junction of the right ventricle and right atrium. The life cycle of T. canis is complex and includes tracheal and somatic migrations of larvae, and they can be found in many tissues throughout the host's body. However, it is rare for adult ascarids to be recovered outside of the small intestine. This is the first report of an adult T. canis inside the pericardial space.


Alendronate sodium-polymeric nanoparticles display low toxicity in gastric mucosal of rats and Ofcol II cells.
The use of bisphosphonates constitutes the gold-standard therapy for the control and treatment of bone diseases. However, its long-term use may lead to gastric problems, which limits the treatment. Thus, this study aimed to formulate a nanostructured system with biodegradable polymers for the controlled release of alendronate sodium. The nanoparticles were characterized, and its gastric toxicity was investigated in rats. The synthesis process proved to be effective for encapsulating alendronate sodium, exhibiting nanoparticles with an average size of 51.02 nm and 98.5% of alendronate sodium incorporation. The release tests demonstrated a controlled release of the drug in 420 min, while the morphological analyzes showed spherical shapes and no apparent roughness. The biological tests demonstrated that the alendronate sodium nanoformulation reversed the gastric lesions, maintaining the normal levels of malondialdehyde and myeloperoxidase. Also, the encapsulated alendronate sodium showed no toxicity in murine osteoblastic cells, even at high concentrations.


Promoter analyses and transcriptional profiling of eggplant polyphenol oxidase 1 gene (SmePPO1) reveal differential response to exogenous methyl jasmonate and salicylic acid.
The transcriptional regulation of multigenic eggplant (Solanum melongena) polyphenol oxidase genes (SmePPO) is orchestrated by their corresponding promoters which mediate developmentally regulated expression in response to myriad biotic and abiotic factors. However, information on structural features of SmePPO promoters and modulation of their expression by plant defense signals are lacking. In the present study, SmePPOPROMOTERs were cloned by genome walking, and their transcription start sites (TSS) were determined by RLM-RACE. Extensive sequence analyses revealed the presence of evolutionarily conserved and over-represented putative cis-acting elements involved in light-regulated transcription, biosynthetic pathways (phenylpropanoid/flavonoid), hormone signaling (abscisic acid, gibberellic acid, jasmonate and salicylate), elicitor and stress responses (cold/dehydration responses), sugar metabolism and plant defense signaling (W-BOX/WRKY) that are common to SmePPOPROMOTER1 and 2. The TSS for SmePPO genes are located 9-15bp upstream of ATG with variable lengths of 5' untranslated regions. Transcriptional profiling of SmePPOs in eggplant seedlings has indicated differential response to methyl jasmonate (MeJA) or salicylic acid (SA) treatment. In planta, while MeJA elicited expression of all the six SmePPOs, SA was only able to induce the expression of SmePPO4-6. Interestingly, in dual treatment, SA considerably repressed the MeJA-induced expression of SmePPOs. Functional dissection of SmePPOPROMOTER1 by deletion analyses using Agrobacterium-mediated transient expression in tobacco leaves has shown that MeJA enhances the SmePPOPROMOTER1-β-glucuronidase (GUS) expression in vivo, while SA does not. Histochemical and quantitative GUS assays have also indicated the negative effect of SA on MeJA-induced expression of SmePPOPROMOTER1. By combining in silico analyses, transcriptional profiling and expression of SmePPOPROMOTER1-GUS fusions, the role of SA on the modulation of MeJA-induced SmePPO1 expression has been elucidated. It is concluded that similar to the coding regions of multigenic SmePPOs, the regulatory elements are also evolutionarily conserved and fall into two distinct sub-classes based on their responses to MeJA and SA.


Clinical Outcomes in Adult Patients With an Anomalous Right Coronary Artery from the Left Sinus of Valsalva.
An anomalous origin of the right coronary artery from the opposite sinus of Valsalva with an intramural course (R-ACAOS-IM) may cause sudden cardiac death in children and adolescents. However, the natural history and management of patients in whom this anomaly is detected later during adulthood remains uncertain. The goals of this study were to assess the impact of an R-ACAOS-IM on the clinical outcomes in an adult population and to determine if adult patients with this anomaly who do not have significant coronary artery disease (CAD) can be managed safely without surgical intervention. A database review identified patients aged >35 years with anomalous coronary arteries diagnosed by cardiac catheterization or coronary computed tomography angiography. The outcomes of patients with R-ACAOS-IM were compared with patients with anomalous left circumflex coronary arteries with retroaortic course (LCx-RA) (an anomaly not associated with ischemic events). The primary outcome was all-cause mortality. The study population consisted of 185 patients aged 59 ± 12 years. Clinical characteristics were similar in the R-ACAOS-IM (n = 88) and LCx-RA (n = 97) groups. At a follow-up of 6.6 ± 4.5 years, there was no difference in mortality (hazard ratio 0.64, 95% confidence interval 0.32 to 1.28, p = 0.20) when adjusted for gender, age, and CAD. A subgroup analysis of 88 patients with no obstructive CAD managed nonoperatively found no difference between the LCx and R-ACAOS-IM groups in mortality (hazard ratio 2.45, 95% confidence interval 0.45 to 13.40, p = 0.30). There was no significant difference between the 2 groups in the composite outcome of death, nonfatal myocardial infarction, or survived cardiac arrest. The outcome of adult patients who have anomalous R-ACAOS-IM are similar to patients who have anomalous LCx-RA with a known benign course. In conclusion, these results suggest that most patients who survive this anomaly into adulthood may be managed conservatively without intervention.


Thioglycollate stimulus modifies lymphocyte metabolism and proliferation. A comparison with lymphocyte activation by Walker 256 tumour implantation.
Key enzyme activities of glycolysis, the pentose-phosphate pathway, the Krebs' cycle and glutaminolysis were measured in lymphocytes obtained from the control (CC), thioglycollate-injected (TG) and Walker 256 tumour-implanted (WT) groups, non-immune and immune inflammatory stimuli, respectively. The rates of incorporation of [2-14C]-thymidine and [5-3H]-uridine into cultured lymphocytes were also determined. The results indicated that the rates of both [2-14C]-thymidine and [5-3H]-uridine incorporation were enhanced in lymphocytes obtained from thioglycollate-injected (by an average of 80 per cent) and tumour-implanted animals (by 2.4-fold) as compared to control rats. Lymphocyte hexokinase activity diminished both in the TG (23 per cent) and WT (61 per cent) groups, whereas glucose 6-phosphate dehydrogenase activity was not altered due to the non-immune inflammatory stimulus, being reduced (23 per cent) in WT rats as compared to CC. The activity of lymphocyte citrate synthase was lowered by thioglycollate (39 per cent) and tumour-implantation (46 per cent). In contrast, glutaminase activity was augmented in lymphocytes from the TG (41 per cent) and was not modified in the WT groups. Taken as a whole, the presence of the Walker 256 tumour did not affect the capacity for glutamine utilization but depressed glucose metabolism in these cells. On the other hand, the non-immune inflammatory stimulus suppressed the activities of glycolysis and the Krebs' cycle and enhanced that of glutaminolysis in lymphocytes.


Interactions of TANGO and leukocyte integrin CD11c/CD18 regulate the migration of human monocytes.
The TANGO gene was originally identified as a new member of the MIA gene family. It codes for a protein of yet unknown function. TANGO revealed a very broad expression pattern in contrast to the highly restricted expression pattern determined for the other family members. The only cells lacking TANGO expression are cells of the hematopoietic system. One of the major differences between mature hematopoietic cells and other tissue cells is the lack of adhesion until these cells leave the bloodstream. In this study, we observed that TANGO expression was induced after adhesion of human monocytic cells to substrate. To understand the mechanism of TANGO function during monocyte adhesion we isolated interacting proteins and found an interaction between TANGO and the leukocyte-specific integrin CD11c. In functional assays, we observed reduced attachment of human monocytic cells to fibrinogen, ICAM-1 and to human microvascular endothelial cells (HMECs) after stimulation with recombinant TANGO protein. Additionally, the migrating capacity of premonocytic cells through fibrinogen or HMECs was increased after stimulation of these cells with recombinant TANGO. Therefore, we suggest that TANGO reduced the attachment to fibrinogen or other cell adhesion molecules. As TANGO does not compete for CD11c ligand binding directly, we hypothesize TANGO function by modulation of integrin activity. Taken together, the results from this study present TANGO as a novel ligand for CD11c, regulating migratory processes of hematopoietic cells.


[Physiotherapeutic treatment in the recuperation of rheumatoid hands].
In restoring the rheumatoid hand, the balneo-physical therapy considers the restrain of the painful and inflammatory phenomena, and the prevention and correction of the deforming lesions with the view to restore the muscle prehension. The final aim is the function restoration and the socio-professional readjustment of the patients. The author presents in detail the devices of physical therapy.


A de novo 1.13 Mb microdeletion in 12q13.13 associated with congenital distal arthrogryposis, intellectual disability and mild dysmorphism.
A girl presented with congenital arthrogryposis, intellectual disability and mild bone-related dysmorphism. Molecular workup including the NimbleGen Human CGH 2.1M platform revealed a 1.13 Mb de novo microdeletion on chromosome 12q13.13 of paternal origin. The deletion contains 33 genes, including AAAS, AMRH2, and RARG genes as well as the HOXC gene cluster. At least one gene, CSAD, is expressed in fetal brain. The deletion partially overlaps number of reported benign CNVs and pathogenic duplications. This case appears to represent a previously unknown microdeletion syndrome and possibly the first description in humans of a disease phenotype associated with copy loss of HOXC genes.


Overexpression of long non-coding RNA00355 enhances proliferation, chemotaxis, and metastasis in colon cancer via promoting GTF2B-mediated ITGA2.
Long non-coding RNAs (LncRNAs) can regulate physiological and pathological functions, exhibiting a wide range of roles in cell biology. Moreover, many lncRNAs are dysregulated in various cancers, including colon cancer. In this study, we investigated the role of the lncRNA LINC00355 in colon cancer, after first establishing its interaction with GTF2B, and ITGA2 on the LncMap database. The predicted relationships between the lncRNA LINC00355, GTF2B, and ITGA2 were identified using luciferase reporter assay, RIP, and ChIP experiments. Western blot analysis and RT-qPCR were applied to determine expression pattern of lncRNA LINC00355 and ITGA2 in colon cancer cells. Additionally, EdU, TUNEL, Cell-adhesion and Transwell assay was used for the detection of the effects of this axis on proliferation, apoptosis, adhesion, chemotaxis and metastasis. LncRNA LINC00355 targeted IGFBP2 through the recruitment of GTF2B. LncRNA LINC00355 was highly expressed in colon cancer cells, and overexpression of lncRNA LINC00355 increased the expression of IGFBP2 and GTF2B, and thereby promoted the proliferation, chemotaxis, invasion, and migration in colon cancer. In summary, downregulation of lncRNA LINC00355 in colon cancer inhibited tumor growth in colon cancer through effects on the GTF2B/IGFBP2 axis.


Ovum recovery and in vitro fertilization in the chimpanzee.
The technique of in vitro fertilization (IVF) is being used to alleviate infertility in women. The potentials of the technique are not limited to this application and could be expanded to include embryo storage and cytogenetic evaluation prior to reimplantation. Nonhuman primate models should be used for development of such techniques. In general, techniques used for human IVF are applicable to the chimpanzee with modifications in culture medium and aspiration techniques as described here. This paper provides the first documentation of IVF in the chimpanzee, a species with significant potential to provide data of value in expansion of application of human IVF.


Risk of Cervical Dysplasia After Colposcopy Care and Risk-Informed Return to Population-Based Screening: A Systematic Review.
This systematic review examined the risk of cervical dysplasia among women who have undergone a colposcopy episode of care to inform their return to population-based cervical screening. PubMed, Embase, and grey literature were searched between January 2000 and 2018. One reviewer screened citations against pre-defined eligibility criteria. A second reviewer verified 10% and 100% of exclusions at title and abstract and at full-text screening, respectively. One reviewer extracted data and assessed methodological quality of included articles; a second reviewer verified these in full. The primary outcome was incidence of cervical intraepithelial neoplasia grade 2 or greater (CIN2+) subsequent to initial colposcopy evaluation. Secondary outcomes included incidence of CIN2+ after negative follow-up test results and performance of follow-up strategies. Results were synthesized narratively. A total of 48 studies were included. The 1- to 5-year CIN2+ risks after colposcopy evaluation ranged from 2.4% to 16.5% among women treated for CIN2+ and from 0.7% to 16.8% among women untreated for CIN grade 1 or less (≤CIN1). Follow-up strategies included single or repeat cytology, human papillomavirus (HPV) testing, or combined HPV/cytology co-testing at various intervals. After negative follow-up test results, risk varied by follow-up strategy for both groups and by referral cytology severity for untreated women. Performance of follow-up strategies varied among treated women. Among untreated women, co-testing demonstrated greater sensitivity than cytology alone. In conclusion, women treated during colposcopy for CIN2+ and women with ≤CIN1 who were referred to colposcopy for low-grade cytology and who did not receive treatment may be able to return to population-based screening after negative co-testing results. Current evidence does not suggest that women untreated for ≤CIN1 who are referred for high-grade cytology be returned to screening at an average risk interval. The optimal strategy for colposcopy discharge needs ongoing evaluation as implementation of HPV testing evolves.


A developmental nephron deficit in rats is associated with increased susceptibility to a secondary renal injury due to advanced glycation end-products.
The aim of this study was to investigate the effects of a secondary renal insult, due to chronic infusion of AGEs on renal function, and on early pathological markers in rats with a developmental nephron deficit. Female Wistar-Kyoto rats were fed a low-protein diet (LPD; 8.7% casein) or a normal-protein diet (NPD; 20% casein) during pregnancy and lactation. Nephron number was estimated in 4-week-old female offspring. Male offspring were allowed to grow to 20 weeks of age, when AGEs derived from BSA (AGE-BSA) or BSA was infused subcutaneously (20 mg kg(-1) day(-1)) for 4 weeks. At 24 weeks, blood pressure, renal function and circulating and renal AGEs were assessed. Real-time PCR was used to investigate early molecular markers of renal pathology. As expected, maternal protein restriction led to reduced nephron endowment in LPD offspring. This alone did not affect blood pressure or lead to hyperfiltration in adulthood. However, when coupled with the secondary renal insult, the expression of the genes encoding transforming growth factor-beta(1) and procollagen III was significantly upregulated in the kidneys. In addition, there was renal accumulation of AGEs in LPD offspring, and this was exacerbated by AGE infusion. Our results demonstrate that the adult kidney with a reduced nephron endowment is more vulnerable to secondary renal insult from AGE-BSA. Since AGE formation is markedly elevated with hyperglycaemia, our findings suggest that a developmental or acquired deficit may render the kidney susceptible to diabetic renal disease.


Evaluation of 3 dimensional space and time filtering on ECG gated 201Tl myocardial images.
Stress 201Tl myocardial images were obtained using a standard ECG gated acquisition protocol for 10 min per view. These images were filtered using a three dimensional space and time filter. The effects of filtering were evaluated by sectorial analysis. Comparing raw and filtered dynamic images, quantification demonstrated that filtering did not produce artefacts. A conventional static image was also obtained as the sum of the series of unfiltered dynamic images. Comparison of raw static and filtered diastolic images indicated that the latter demonstrated myocardial abnormalities more clearly (P less than 0.01) in 33 patients. Improvement in the signal to noise ratio produced by filtering made cinematic display and visual analysis possible which was not feasible with raw gated images. Clinical evaluation is in progress.


Changes in venous flow and intra tracheal flow in fetal breathing movements.
Using pulsed Doppler ultrasound combined with a real-time B-mode image, changes in the central venous blood flow and tracheal fluid flow were recognized during fetal breathing movements. The blood flow in the umbilical vein was increased with fetal inspiration in which the abdominal wall of fetus moved inward, and decreased with expiration in which the abdominal wall moved outward. Velocity in the fetal vena cava revealed a complex blood flow, in accordance with both fetal cardiac motions and breathing movements. The tracheal flow velocity during fetal breathing was measured at a maximum of 40 cm s-1 and the flow volume was estimated at a maximum of 6 ml breath-1 in the matured fetus.


A novel G-quadruplex motif modulates promoter activity of human thymidine kinase 1.
G-quadruplex motifs constitute unusual DNA secondary structures formed by stacking of planar hydrogen-bonded G-tetrads. Recent genome-wide bioinformatics and experimental analyses have suggested the interesting possibility that G-quadruplex motifs could be cis-regulatory elements. Here, we identified a characteristic potential G-quadruplex-forming sequence element within the promoter of human thymidine kinase 1 (TK1). Our NMR, UV and CD spectroscopy and gel electrophoresis data suggested that this sequence forms a novel intramolecular G-quadruplex with two G-tetrads in K(+) solution. The results presented here indicate the role of this G-quadruplex motif in transcription of TK1 in cell-based reporter assays. Specific nucleotide substitutions designed to destabilize the G-quadruplex motif resulted in increased promoter activity, supporting direct involvement of the G-quadruplex motif in transcription of TK1. These studies suggest that the G-quadruplex motif may be an important target for controlling critical biological processes, such as DNA synthesis, mediated by TK1.


Relation Between Change in Renal Function and Cardiovascular Outcomes in Atorvastatin-Treated Patients (from the Treating to New Targets [TNT] Study).
Statins may have nephroprotective as well as cardioprotective effects in patients with cardiovascular disease. In the Treating to New Targets (TNT) study (NCT00327691), patients with coronary heart disease (CHD) were randomized to atorvastatin 10 or 80 mg/day and followed for 4.9 years. The relation between intrastudy change in estimated glomerular filtration rate (eGFR) from baseline and the risk of major cardiovascular events (MCVEs, defined as CHD death, nonfatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke) was assessed among 9,500 patients stratified by renal function: improving (change in eGFR more than +2 ml/min/1.73 m(2)), stable (-2 to +2 ml/min/1.73 m(2)), and worsening (less than -2 ml/min/1.73 m(2)). Compared with patients with worsening renal function (1,479 patients, 15.6%), the rate of MCVEs was 28% lower in patients with stable renal function (2,241 patients, 23.6%) (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.60 to 0.87; p = 0.0005) and 64% lower in patients with improving renal function (5,780 patients, 60.8%; HR 0.36; 95% CI 0.30 to 0.43; p <0.0001). For each 1 ml/min/1.73 m(2) increase in eGFR, the absolute reduction in the rate of MCVEs was 2.7% (HR 0.973; 95% CI 0.967 to 0.980; p <0.0001). An absolute MCVE rate reduction per 1 ml/min/1.73 m(2) increase in eGFR of 2.0% was reported with atorvastatin 10 mg and 3.3% with atorvastatin 80 mg. In conclusion, intrastudy stabilization or increase in eGFR in atorvastatin-treated patients with CHD from the TNT study was associated with a reduced rate of MCVEs. Statin-treated CHD patients with progressive renal impairment are at high risk for future cardiovascular events.


Correlation of N-myc downstream-regulated gene 1 subcellular localization and lymph node metastases of colorectal neoplasms.
In colorectal neoplasms, N-myc downstream-regulated gene 1 (NDRG1) is a primarily cytoplasmic protein, but it is also expressed on the cell membrane and in the nucleus. NDRG1 is involved in various stages of tumor development in colorectal cancer, and it is possible that the different subcellular localizations may determine the function of NDRG1 protein. Here, we attempt to clarify the characteristics of NDRG1 protein subcellular localization during the progression of colorectal cancer. We examined NDRG1 expression in 49 colorectal cancer patients in cancerous, non-cancerous, and corresponding lymph node tissues. Cytoplasmic and membrane NDRG1 expression was higher in the lymph nodes with metastases than in those without metastases (P<0.01). Nuclear NDRG1 expression in colorectal neoplasms was significantly higher than in the normal colorectal mucosa, and yet the normal colorectal mucosa showed no nuclear expression. Furthermore, our results showed higher cytoplasmic NDRG1 expression was better for differentiation, and higher membrane NDRG1 expression resulted in a greater possibility of lymph node metastasis. These data indicate that a certain relationship between the cytoplasmic and membrane expression of NDRG1 in lymph nodes exists with lymph node metastasis. NDRG1 expression may translocate from the membrane of the colorectal cancer cells to the nucleus, where it is involved in lymph node metastasis. Combination analysis of NDRG1 subcellular expression and clinical variables will help predict the incidence of lymph node metastasis.


Density-dependent effects on hatching success of the olive ridley turtle, Lepidochelys olivacea.
Historically, the olive ridley arribada at Playa Nancite, Costa Rica, was one of the largest olive ridley arribadas in the eastern Pacific with 70,000 nesting females in a year. Recently the Nancite arribada drastically declined. We hypothesized that the population decline at Playa Nancite could have been due to low hatching success as a result of the high density of nests on the beach, such that recruitment to the population was insufficient to balance losses. To test this hypothesis, we examined density-dependent effects on hatching success and their underlying mechanisms by experimentally manipulating nest densities in experimental plots on the nesting beach. We set up four nest-density treatments in five experimental blocks. We measured effects of density on hatching success, CO(2) and O(2) concentrations and temperature both within nests and in sand adjacent to nests frequently during incubation. Experimental nest densities affected hatching success with the highest density having the lowest hatching success. Higher nest density led to lower O(2) levels and higher CO(2) levels in the nest with greater changes in the latter part of the incubation. Highest temperatures occurred in high-density areas. Temperatures were lower in sand surrounding the nest than in the nest. Effects of density on temperature, CO(2) and O(2) were confirmed at a naturally high-density nesting beach, Playa La Flor, Nicaragua. Long-term failure in production of hatchlings due to historic high densities may have contributed to the decline of arribadas on Playa Nancite. Thus, density-dependent population control would have operated at the embryonic life stage in this population of olive ridley turtles.


Comparison of the ultrastructure of stimulated and unstimulated mechanoreceptors in the taste hairs of the blowfly Phaenicia serricata.
The structure of mechanoreceptors at the base of labellar taste hairs of the blowfly Phaenicia serricata were examined in stimulated and unstimulated conditions (i.e. with the hair bent or unbent). Physiological recordings from the mechano-receptor showed that the receptors responded when the hair is bent dorsally or ventrally and when the hair is bent at extreme angles. These conditions are the same as those placed on hairs in the anatomical studies. Bending the hair toward the ventral labellar surface caused the hair base to compress and indent the tubular body and its surrounding membrane and sheath at the distal end of the mechanoreceptor dendrite. In compressed tubular bodies, microtubules oriented longitudinally were bent and separated a greater distance from each other. Separation as much as 70 nm was observed in compressed tubular bodies as compared with a maximum of 26 nm between micro-tubules in tubular bodies of unbent hairs. The dense amorphous material between microtubules of compressed tubular bodies formed prominent bridges 18 nm thick connecting the microtubules at intervals of 48-74 nm. Thin 10 nm filaments were also evident in the spaces between microtubules. When the hair was bent toward the proximal end of the proboscis, the tip of the tubular body was bent about 15 degrees. The tubular body appears to function as a firm but resilient structure over which the dendritic membrane can be stretched during mechanostimulation. Comparison of morphology of bent and unbent hairs suggests a means by which mechanical force from the movement of the hair is transferred to the receptors by structures in the hair socket region. No differences were found in ciliary structures of stimulated and unstimulated receptors.


Nitroalkanes as thioacyl equivalents to access thioamides and thiopeptides.
Thioamides are an important, but a largely underexplored class of amide bioisostere in peptides. Replacement of oxoamide units with thioamides in peptide therapeutics is a valuable tactic to improve biological activity and resistance to enzymatic hydrolysis. This tactic, however, has been hampered by insufficient methods to introduce thioamide bonds into peptide or protein backbones in a site-specific and stereo-retentive fashion. In this work, we developed an efficient and mild thioacylation method to react nitroalkanes with amines directly in the presence of elemental sulfur and sodium sulfide to form a diverse range of thioamides in high yields. Notably, this convenient method can be employed for the controlled thioamide coupling of multifunctionalized peptides without epimerization of stereocenters, including the late stage thioacylation of advanced compounds of biological and medicinal interest. Experimental interrogation of postulated mechanisms currently supports the intermediacy of thioacyl species.


Disordered cerebro-vascular physiology in aneurysmal subarachnoid haemorrhage.
The technical problems of surgery for anterior circle aneurysm have in large measure been solved. The problem of reduced perfusion to the brain which characterises the patient with aneurysmal subarachnoid haemorrhage in a poor clinical condition demands more subtle physiological handling. It appears likely that maintenance of an intact cell membrane and blood brain barrier may be aided by the exhibition of pre and post-operative steriods, and that concentration on regional perfusion should be the main aim in post-operative management of such cases. This demands maintenance of adequate blood volume, avoidance of platelet stickiness, and utilisation of the pathological paralysis of autoregulation to improve flow to ischaemic zones by hypertensive agents if necessary. The possibility that early operation with evacuation of blood from the basal cisterns may in the end prevent the vascular damage and disordered vaso-reactivity which encourages the development of transient ischaemic deficits, is a concept which has to be actively pursued. The problem is a continuing one which has bedevilled aneurysm surgery for 25 years, but the omens suggest that a solution is appreciably nearer at hand.


Association of testosterone, insulin-like growth factor-I, and C-reactive protein with metabolic syndrome in Chinese middle-aged men with a family history of type 2 diabetes.
Age-related declines in testosterone and IGF-I are associated with deposition of visceral fat, a component of the metabolic syndrome (MES). Testosterone and IGF-I may interact with familial disposition to diabetes mellitus to increase the association with MES. We conducted a cross-sectional cohort study. The study was conducted in a university teaching hospital. Study subjects included 179 middle-aged men with a family history of diabetes (FH) (aged 39.1 +/- 8.1 yr) and 128 men without FH (aged 43.8 +/- 8.5 yr). Clinical characteristics, frequency of MES using the World Health Organization criteria with Asian definitions of obesity (body mass index > or = 25 kg/m2), and serum levels of total testosterone, IGF-I, and high-sensitive C-reactive protein (hs-CRP) were measured. Men with FH had higher frequency of MES than those without FH [39.1 vs. 23.4% (P = 0.004)]. On multivariate analysis, smoking (former and current smokers), low total testosterone, and IGF-I but elevated hs-CRP levels explained 35% of the MES variance in men with FH. The frequency of MES increased with declining tertiles of total testosterone and IGF-I but increasing tertiles of hs-CRP. After adjustment for age and smoking history, subjects with all three risk factors had a 13-fold increase in risk association with MES compared with those without hormonal and inflammatory risk factors. These risk associations were not found in men without FH in whom only smoking (ex and current) and low total testosterone level were independent predictors for MES, which explained 14% of the variance. Clustering of FH, hormonal abnormalities, and high hs-CRP is associated with MES in Chinese middle-aged men.


Magnetic resonance imaging abnormalities in children with epilepsy.
The aim of this study is to analyze the proportional distribution of epilepsy and epileptic syndromes in children and to describe the magnetic resonance imaging (MRI) abnormalities found in these patients. Data from 457 children aged 1 month to 15 years at the time of diagnosis of epilepsy were recorded. A routine MRI has been requested in all patients with epilepsy at diagnosis according to a standardized pediatric seizure protocol. Abnormalities on MRI were classified as either significant or non-significant (standardized scoring system). International League Against Epilepsy criteria were used for diagnoses. The prevalence of significant MRI abnormalities was 21.9% (in infants 42.3%, in childhood 18.2%, and in adolescents 15.9%). The most common abnormalities included white-matter lesions (27.6%), volume loss (19.6%), gray-matter lesions (19.6%), and ventricular enlargement (12%). The use of MRI and a reliable standardized scoring system at diagnosis of epilepsy in children identified a high rate of significant abnormalities findings. This may have important implications for practice guidelines in this population.


Triage and management of cranial injuries.
This article discusses basic head and intracranial CNS anatomy, cerebral physiology, and classifications of head injury. Management principles and the practice of head-injury evaluation are reviewed and supplemented by the presentation of selected head-injury scenarios. The optimal evaluation and treatment of the head-injured patient is predicated on initially following established ATLS principles and preventing secondary injury. Once specific injuries have been identified, maintenance of cerebral perfusion and oxygenation is the key to maximizing patient outcomes, and this often requires measurement and treatment of ICP values. When significant mass lesions are identified or ICP elevations become refractory to medical intervention, surgical intervention is necessary.


Surgical management of gastric cancer: review and consideration for total care of the gastric cancer patient.
Surgical therapy remains the most effective modality in the treatment of gastric cancer. Staging laparoscopy with laparoscopic ultrasound may increase the accuracy of staging and prevent patients with unresectable gastric cancer from undergoing unnecessary operations. Resection of proximal and distal gastric cancer is best accomplished with an appropriate gastrectomy that ensures adequate resection margins. A D2 lymphadenectomy can be performed safely and facilitates the resection of the minimum 15 lymph nodes required for adequate staging. Adjacent organ resection should be used only in highly selected patients with R0 resection as the goal. Palliative operations offer improved quality of life and symptom relief in patients with metastatic disease. Appreciation of postoperative quality of life after gastric resection facilitates appropriate and effective preoperative counseling. Surgical outcomes may be influenced by hospital volume and rate of adequate lymph node assessment.


Cortical involvement in essential tremor with and without rest tremor: a machine learning study.
There is some debate on the relationship between essential tremor with rest tremor (rET) and the classic ET syndrome, and only few MRI studies compared ET and rET patients. This study aimed to explore structural cortical differences between ET and rET, to improve the knowledge of these tremor syndromes. Thirty-three ET patients, 30 rET patients and 45 control subjects (HC) were enrolled. Several MR morphometric variables (thickness, surface area, volume, roughness, mean curvature) of brain cortical regions were extracted using Freesurfer on T1-weighted images and compared among groups. The performance of a machine learning approach (XGBoost) using the extracted morphometric features was tested in discriminating between ET and rET patients. rET patients showed increased roughness and mean curvature in some fronto-temporal areas compared with HC and ET, and these metrics significantly correlated with cognitive scores. Cortical volume in the left pars opercularis was also lower in rET than in ET patients. No differences were found between ET and HC. XGBoost discriminated between rET and ET with mean AUC of 0.86 ± 0.11 in cross-validation analysis, using a model based on cortical volume. Cortical volume in the left pars opercularis was the most informative feature for classification between the two ET groups. Our study demonstrated higher cortical involvement in fronto-temporal areas in rET than in ET patients, which may be linked to the cognitive status. A machine learning approach based on MR volumetric data demonstrated that these two ET subtypes can be distinguished using structural cortical features.


A new parasitic copepod species of Tautochondria (Siphonostomatoida: Hyponeoidae), found in the narrowmouthed catshark Schroederichthys bivius from the Strait of Magellan.
Hyponeoidae is a copepod family that is rare around the world, with only three species described until now. Recently, a hyponeoid copepod was found in the narrowmouthed catshark, Schroederichthys bivius, from Chile, which has not been formally described. The objective of this study is to describe morphologically a new species of Hyponeoidae, from samples of the Strait of Magellan, Southern Chile. Also, a genetic analysis, based on the COI gene, was used to determine the relatedness of the new hyponeoid species to other copepods from Siphonostomatoida, which were available in the GenBank platform. The new species belongs to the genus Tautochondria and is here described as T. magellanica n. sp. This species differs from T. dolichoura mainly in the presence of long process at each side of the buccal cone, the absence of lobes on the head and short processes on the genital complex. According to the genetic sequences, T. magellanica n. sp. was not closely related to any other species. Therefore, this result confirms that Hyponeoidae is a separate family. However, the relatedness to other genera in Siphonostomatoida is still unknown.


A lateral extra-articular tenodesis for anterior cruciate ligament deficiency of the knee.
This article reviews patients with documented anterior cruciate ligament-deficient knees. Historical features are emphasized, and a rating system is provided. A lateral tenodesis is described, with timing of the repair and proper rehabilitation stressed.


Endovascular training with animals versus virtual reality systems: an economic analysis.
To assess the relative costs of a virtual reality (VR) laboratory and an animal laboratory for endovascular skills training. Cost data extracted from a previous experiment was used to perform a financial analysis according to the guidelines published by the National Institutes of Health. The analysis compared the purchase or rental of a Procedicus Vascular Interventional System Trainer to the rental of an animal laboratory. The VR laboratory course cost $3,434 per trainee versus $4,634 in the animal laboratory according to the purchase-versus-rental analysis. The cost ratio was 0.74 in favor of the VR laboratory. Cost ratio sensitivity analysis ranged from 0.25 in favor of the VR laboratory to 2.22 in favor of the animal laboratory. The first-year potential savings were $62,410 assuming exclusive use of the VR laboratory. The 5-year training savings totaled $390,376, excluding the $60,000 residual value of the simulator. Simulator rental reduced the course price to $1,076 per trainee and lowered the cost ratio to 0.23 in favor of the VR laboratory. Findings of sensitivity analysis ranged from 0.08 to 0.70 in favor of the VR laboratory. The first-year and 5-year potential national savings increased to $185,026 and $1,013,238, respectively. Although evidence remains sparse that the training of interventional skills in artificial environments translates to better performance in human procedures, there are good pedagogic grounds on which to believe that such training will become increasingly important. The present comparison of the direct costs of two such models suggests that VR training is less expensive than live animal training.


Initial orthostatic hypotension among patients with unexplained syncope: An overlooked diagnosis?
Initial orthostatic hypotension (IOH) is a clinical syndrome of transient orthostatic hypotension that is defined as a drop in blood pressure of >40 mm Hg systolic and/or >20 mm Hg diastolic within 15 s after standing, accompanied by symptoms of cerebral hypoperfusion, but without sustained orthostatic hypotension (blood pressure decrease >20/10 mm Hg after 1-3 min of standing). As the etiology of syncope remains unknown in a large proportion of patients, we hypothesized that IOH is highly prevalent among patients with unexplained syncope. We studied 250 consecutive outpatients with unexplained syncope that were evaluated in the syncope-unit of our tertiary referral hospital. We measured hemodynamic changes in response to active standing using a beat-to-beat blood pressure measurement device, first after lying supine for >5 min and then after squatting for 30 s. 11.2% of the patients were diagnosed with syncope due to IOH, with a mean fall in blood pressure of 47.4 ± 12.5/29.0 ± 10.7 mm Hg within 15 s after standing up. Therefore, IOH was the second commonest cause of syncope in our cohort. 46.2% of the patients diagnosed with syncope due to IOH used antihypertensive drugs, mostly betablockers (41.6%) and/or tamsulosin (24.9%). The squatting-to-standing-test in addition to the lying-to-standing-test resulted in only 3 additional patients diagnosed with syncope due to IOH. IOH is highly prevalent among patients with previously unexplained syncope. Therefore, beat-to-beat blood pressure measurement should be considered in patients with unexplained syncope.


Unprecedented photochemical induced cascading rearrangement of the 3-azabicyclo[3.3.1]nonane skeleton.
Certain 3-azabicyclo[3.3.1]nonane derivatives undergo unprecedented stereospecific skeletal cleavage when subjected to light affording a novel heterotricyclic skeleton.


Trace Aldehydes in Solid Oral Dosage Forms as Catalysts for Nitrosating Secondary Amines.
Nitrosamine impurities may form during drug substance manufacturing processes. Here, we focus on nitrosamine impurity level growth in oral drug products during long term stability studies. Nitrosamine growth mechanisms in oral dosage forms are typically framed as due to nitrosating agents that can be formed in solutions of nitrous acid with a required pH value of around pH 5 or below. We strive in this work to bring awareness to pharmaceutical scientists that formaldehyde, common in oral dosage form excipients, has previously been shown in solution to catalyze the reaction between secondary amines and nitrite ion to give nitrosamine products. This mechanism operates at pH ∼6 and higher. We attempt to re-frame the solution work as relevant to pharmaceutical solid dosage forms. Recent examples of solid dosage form product recalls are used to demonstrate the formaldehyde catalyzed nitrosation pathway operating in the solid state.


Organically Modified Nanoclay Filled Thin-Film Nanocomposite Membranes for Reverse Osmosis Application.
This study validates, for the first time, the effectiveness of two nanoclays, that is, cloisite (CS)-15A and montmorillonite (MNT) at the polyamide (PA) active layer in the reverse osmosis (RO) membrane. Cloisite-15A is natural montmorillonite modified with dimethyl dihydrogenated tallow quaternary ammonium salt. Thin-film composite (TFC) membranes were fabricated by the interfacial polymerization (IP) process between the trimesoylchloride (TMC)-n-hexane solution and m-phenylenediamine (MPD)-aqueous solution; the IP process took place on a polysulfone support sheet. The two types of nanoparticles were added in various weight ratios (0.005 wt.%-0.04 wt.%) in the n-hexane solution of TMC. Different characterizations like X-ray diffraction (XRD), contact angle, transmission electron microscopy (TEM), and membrane performance tests were performed to analyse the membrane properties. Both XRD and TEM studies proved that the two nanoclays are successfully anchored at the different sites of the PA layer. CS-15A could accelerate the water flux from 15 to 18.65 L/m2·h with NaCl rejection enhancement from 72% to 80%, relative to the control membrane. Conversely, MNT also enhanced the flux from 15 to 40 L/m2·h, but NaCl rejection reduced from 70% to 23%. The mechanism of water uptake in nanoclays was also discussed. The results pave the way for a complete future study, in which these phenomena should be studied in great detail.


Differential expression of genes involved in Bengal macrothrombocytopenia (BMTCP).
Bengal macrothrombocytopenia (BMTCP) is a giant platelet disorder with mild to moderate thrombocytopenia, clinically characterized by mild bleeding symptoms to totally asymptomatic condition. The pathophysiological mechanism of this condition is not fully understood yet. In the present study, 5 subjects (P1-P5) with BMTCP whose platelet counts ranged between 36140X10(9)/l and mean platelet volume (MPV)13.5-16.1fl were analyzed for differential gene expression of platelets by suppressive subtractive hybridization (SSH) technique. Four genes i.e. myotubularin related protein 9 (MTMR9), iron responsive element binding protein 2 (IREB2), alpha tubulin(TUBA) and tyrosine kinase ligand (TKL) were found to be differentially expressed in patient platelets as compared to that of normal healthy controls which was further confirmed by quantitative RT PCR analysis. The study highlights a multi-factorial etiology for BMTCP which is widely prevalent in the northeastern region of the Indian subcontinent.


Dynamic Bayesian network modeling for longitudinal brain morphometry.
Identifying interactions among brain regions from structural magnetic-resonance images presents one of the major challenges in computational neuroanatomy. We propose a Bayesian data-mining approach to the detection of longitudinal morphological changes in the human brain. Our method uses a dynamic Bayesian network to represent evolving inter-regional dependencies. The major advantage of dynamic Bayesian network modeling is that it can represent complicated interactions among temporal processes. We validated our approach by analyzing a simulated atrophy study, and found that this approach requires only a small number of samples to detect the ground-truth temporal model. We further applied dynamic Bayesian network modeling to a longitudinal study of normal aging and mild cognitive impairment--the Baltimore Longitudinal Study of Aging. We found that interactions among regional volume-change rates for the mild cognitive impairment group are different from those for the normal-aging group.


Using continuous DNA interpretation methods to revisit likelihood ratio behaviour.
Continuous DNA interpretation systems make use of more information from DNA profiles than analysts have previously been able to with binary, threshold based systems. With these new continuous DNA interpretation systems and a new, more powerful, DNA profiling kit (GlobalFiler) there is an opportunity to re-examine the behaviour of a commonly used statistic in forensic science, the likelihood ratio (LR). The theoretical behaviour of the LR has been known for some time, although in many instances the behaviour has not been able to be thoroughly demonstrated due to limitations of the biological and mathematical models being used. In this paper the effects of profile complexity, replicate amplifications, assuming contributors, adding incorrect information, and adding irrelevant information to the calculation of the LR are explored. The empirical results are compared to theoretical expectations and explained. The work finishes with the results being used to dispel common misconceptions around reliability, accuracy, informativeness and reproducibility.


Testicular steroidogenesis after human chorionic gonadotropin desensitization in rats.
When a single injection of 500 I.U. of human chorionic gonadotropin (hCG) is given to rats there is an initial acute rise of plasma testosterone and of testicular content for both cyclic AMP and testosterone. This response correlates with an increase in both lyase and 17 alpha-hydroxylase activities. Thereafter both plasma and testicular testosterone decline and do not increase after a second injection of hCG. During this period of desensitization, isolated Leydig cells were insensitive to the steroidogenic stimulatory effect of both hCG and dibutyryl cyclic AMP. The post-cyclic AMP block is not due to an alteration of the cyclic AMP-dependent protein kinase but it is correlated with a decrease in both lyase and 17 alpha-hydroxylase activities of the Leydig cell's microsomes. This decrease is not caused by the absence of the recently described cytosol activator of this enzyme because its addition did not restore the enzymatic activity. Within 60 to 96 h after hCG injection there was a spontaneous increase of both plasma and testicular testosterone and this parallels the recovery of lyase and 17 alpha-hydroxylase activities. These results suggest that both enzymatic activities are regulated, directly or indirectly, by hCG, and that this is partly responsible for the hCG-induced steroidogenic refractoriness of Leydig cells.


Molecular phylogeny and species delimitation within the ciliate genus Spirostomum (Ciliophora, Postciliodesmatophora, Heterotrichea), using the internal transcribed spacer region.
Morphological and molecular delimitation of Spirostomum species is currently under debate. We addressed species boundaries within the genus Spirostomum, using the ITS1-5.8S-ITS2 region and the secondary structure of the ITS2 molecule, and 18S and 28S (D1D2) sequences additionally. The Spirostomum ITS region is among the shortest within the ciliates hitherto studied. The Spirostomum ITS2 molecule matches the "ring model", but exhibits only two helices radiating from a common loop. According to comparative analyses, they very likely correspond to helices II and III of other eukaryotes. Our phylogenetic analyses of the ITS region revealed a complex genealogical structure within the genus Spirostomum. However, boundaries among Spirostomum species could not be unambiguously determined either by phylogenetic trees, networks or sequence divergence cutoffs, because ITS2 sequences transcended species boundaries of the following morphospecies: S. ambiguum, S. minus, S. subtilis and S. teres. According to molecular diversity analysis, this is very likely caused by polymorphism in S. minus and S. teres, and by the lack of variability in S. ambiguum and S. subtilis. No compensatory base changes (CBCs) were detected in helices of the ITS2 molecule between different Spirostomum species, documenting that CBC analysis per se is not able to effectively discriminate Spirostomum species.


Evolution of MHC class II beta chain-encoding genes in the Lake Tana barbel species flock (Barbus intermedius complex).
Major histocompatibility complex (MHC) class II protein polymorphism is maintained in allelic lineages which evolve in a trans-specific manner, passing from one species to descendant species. Selection pressure on peptide binding residues should be greatest during speciation, when organisms move into new environments and their MHC molecules encounter new pathogens. The isolation of MHC genes from teleost fishes, the most diverse group of vertebrates, has created possibilities for testing this hypothesis. The large barbels of Lake Tana have undergone an adaptive radiation within the last 5 million years, producing 14 morphotypes which inhabit different ecological niches within the lake. We studied the variability in class II beta chain-encoding genes of four of these morphotypes using polymerase chain reaction amplification and DNA sequencing. The sequences obtained were orthologous to four of the known class II genes from the common carp, from which barbels diverged approximately 32 million years ago. When subjected to phylogenetic analysis, the 48 sequences clustered into groups which represent allelic lineages. A comparison of nonsynonymous and synonymous substitutions between the peptide binding region codons and non-peptide binding region codons of these sequences revealed that they are under strong selective pressure.


A new species of the genus Amphicteis Grube, 1850 (Annelida, Ampharetidae) from the Yellow Sea, China, together with a redescription of A. dalmatica Hutchings & Rainer, 1979.
A new species of the ampharetid genus Amphicteis, A. hwanghaiensis sp. nov., is described based on material from the Yellow Sea. The new species is characterized by the possession of long, stout, golden paleae with blunt tips, digitiform rudimentary notopodia on the abdominal uncinigers, uncini with a subrostral process, and a narrow rectangular hump separating branchial groups. Amphicteis dalmatica was redescribed from type materials at the Australian Museum, Sydney, and the differences between A. dalmatica and A. hwanghaiensis sp. nov. are discussed. A key to distinguish Amphicteis species described or reported in Western Pacific waters is provided.


Vitamin E prevents cell death induced by mild oxidative stress in chicken skeletal muscle cells.
Apoptosis and necrosis are two forms of cell death that can occur in response to various agents and oxidative damage. In addition to necrosis, apoptosis contributes to muscle fiber loss in various muscular dystrophies as well participates in the exudative diathesis in chicken, pathology caused by dietary deficiency of vitamin E and selenium, which affects muscle tissue. We have used chicken skeletal muscle cells and bovine fibroblasts to study molecular events involved in the cell death induced by oxidative stress and apoptotic agents. The effect of vitamin E on cell death induced by oxidants was also investigated. Treatment of cells with anti-Fas antibody (50 to 400 ng/mL), staurosporine (0.1 to 100 microM) and TNF-alpha (10 and 50 ng/mL) resulted in a little loss of Trypan blue exclusion ability. Those stimuli conducted cells to apoptosis detected by an enhancement in caspase activity upon fluorogenic substrates but this activity was not fully blocked by the caspase inhibitor Z-VAD-fmk. Oxidative stress induced by menadione (10, 100 and 250 muM) promoted a significant reduction in cell viability (10%, 20% and 35% for fibroblasts; 20%, 30% and 75% for muscle cells, respectively) and caused an increase in caspase activity and DNA fragmentation. H2O2 also promoted apoptosis verified by caspase activation and DNA fragmentation, but in higher doses induced necrosis. Vitamin E protected cells from death induced by low doses of oxidants. Although it was ineffective in reducing caspase activity in fibroblasts, this vitamin diminished the enzyme activity in muscle cells. These data suggested that oxidative stress could activate apoptotic mechanisms; however the mode of cell death will depend on the intensity and duration of the stimulus, and on the antioxidant status of the cells.


What if the worst consequences of COVID-19 concerned non-COVID patients?
We highlight in this short article the side-effects of COVID-19 pandemic on the management of non-COVID patients, with potential detrimental and irreversible complications. We thus propose adjusted strategies to deal with both COVID and non-COVID patients.


Accuracy of pedicle screw placement in the thoracic and lumbosacral spines using O-arm-based navigation versus conventional freehand technique.
The accuracy and safety of pedicle screw insertion was markedly improved with the introduction of intraoperative three-dimensional navigation system during the last decade. This study aimed to evaluate the accuracy of pedicle screw placement using O-arm-based navigation system versus conventional freehand technique. We reviewed the accuracy of 341 thoracic (n = 173) and lumbosacral (n = 168) pedicle screws placed in 60 consecutive patients using either O-arm-based navigation or freehand technique in the Department of Neurosurgery of Beijing Tsinghua Changgung Hospital between January 2015 and June 2018. Patient-specific characteristics, treatment-related characteristics, and screw-specific accuracy were analyzed. The accuracy of pedicle screw placement was measured by Gertzbein-Robbins scale and screw grades A and B were clinically acceptable. One hundred ninety-one screws were inserted in the O-arm-based navigation group and 150 in the freehand group. One hundred eighty-three (95.81%) clinically acceptable screws were placed in the navigation group and 135 (90.00%) in the freehand group (p = 0.034). Twenty-three (6.74%) screw revisions were performed in the two groups (8 screws in the navigation group and 15 screws in the freehand group) and significant difference was observed in thoracic spine (p = 0.018), while no statistical significance was presented in lumbosacral spine (p > 0.05). Twenty-four (12.57%) screws in the navigation group and 24 (16.00%) in the freehand group violated the cortex (p > 0.05). Medial screw deviation was the most common problem in the two groups. The O-arm-based navigation exhibits higher accuracy for pedicle screw insertion than the freehand insertion technique.


Correction to: Electroacupuncture induces antihyperalgesic effect through endothelin-B receptor in the chronic phase of a mouse model of complex regional pain syndrome type I.
The original version of this article contains an error. The Author Francisco José Cidral-Filho incorrectly listed as Francisco José Cidra-Filho. The correct spelling is presented above. The original article has been corrected.


The tumor microenvironment.
The concept of the tumor microenvironment, developed from Paget's "seed and soil" theory is made up of the cancer cells, the stromal tissue, and the extracellular matrix. In this mini-review, each of the components of this dynamic network will be examined. We will show that there are a multitude of complex interactions and a host of molecules involved in tumorogenesis and metastasis. We will further illustrate this notion with examples from the tumor microenvironment of breast cancer. Lastly, we conclude with thoughts about how this will influence the surgical field with examples of therapeutic agents already in use that target aspects of this microenvironment.


Anticardiolipin and anti-beta2-glycoprotein-I antibodies in preeclampsia.
To estimate whether antiphospholipid antibodies, specifically anticardiolipin and anti-beta(2)-glycoprotein-I antibodies, are associated with preeclampsia. Plasma was prospectively obtained from four groups of pregnant women: those with 1) mild preeclampsia (n = 109); 2) severe preeclampsia (n = 134); 3) hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (n = 57); and 4) normotensive controls (n = 100). Anticardiolipin and anti-beta(2)-glycoprotein-I levels were determined by enzyme-linked immunoassay. Subjects with mild preeclampsia, severe preeclampsia, and HELLP syndrome did not have significantly elevated levels of immunoglobulin G (IgG) and IgM anticardiolipin and anti-beta(2)-glycoprotein-I antibodies compared with normotensive controls (P >.05, Kruskal-Wallis). Similarly, subjects with mild preeclampsia, severe preeclampsia, and HELLP syndrome did not have a significantly higher proportion of women testing positive for each autoantibody compared with normotensive controls (chi(2)). The proportion of patients testing positive for anticardiolipin and anti-beta(2)-glycoprotein-I antibodies were similar in patients with preeclampsia developing before and after 34 weeks' gestation (chi(2)). Circulating levels of both anticardiolipin and anti-beta(2)-glycoprotein-I antibodies were not increased in patients with mild preeclampsia, severe preeclampsia, or HELLP syndrome compared with normotensive controls. Our data do not support routine testing for anticardiolipin and anti-beta(2)-glycoprotein-I antibodies in women with preeclampsia.


Pseudolymphoma of the liver: a case report and literature review.
Pseudolymphoma is a benign lymphocytic tumor-like lesion, and its occurrence in the liver is rare. Here, we report the case of a 78-year-old woman with pseudolymphoma of the liver. She had a history of tremors for several years. Therefore, she underwent computed tomography (CT) for screening, and liver tumors were incidentally identified. She did not have any history of liver disease. Liver function test results and tumor marker levels were all within normal limits, and viral markers for hepatitis were negative. Contrast-enhanced CT revealed four nodules measuring up to 13 mm in diameter with ring enhancement in both lobes of the liver. On magnetic resonance imaging, the lesions showed slightly high intensity on T2-weighted images and high intensity on diffusion-weighted images. Because of atypical imaging findings, the tumors could not be definitively diagnosed. Therefore, we performed laparoscopic limited resection of segments 2, 3, 4, and 8 of the liver. The final pathological diagnosis was pseudolymphoma of the liver. The patient has had no signs of recurrence for 6 months after the surgery. Although pseudolymphoma of the liver is rare, it is necessary to consider it in the differential diagnosis of a liver tumor.


[Differences of water barrier function between keloid and its surrounding normal skin in patients with keloids and its related mechanism].
Objective: To compare the differences of water barrier function between keloids and its surrounding normal skin in patients with keloids, and to explore the primary mechanism. Methods: A cross-sectional observational study was conducted. From October 2020 to March 2021, 30 patients with keloids who met the inclusion criteria visited Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, including 18 females and 12 males, aged 20-48 years. The transepidermal water loss (TEWL) of their keloids and the surrounding normal skin of the 30 patients were measured by multi probe adapter on the reception day. The keloid tissues and normal skin of 5 patients after keloid repair surgery were processed for hematoxylin-eosin staining to measure the thickness of epidermis. Immunohistochemistry was performed on samples from 3 of those 5 patients to detect the expressions of cytokeratin-10, involucrin, and filaggrin in keloids and normal skin. Data were statistically analyzed with paired sample t test and independent sample t test. Results: On the reception day, the TEWL of keloids of 30 patients was 9.0 (6.9, 13.4) g·m-2·h-1 and the TEWL of the normal skin was 8.1 (6.4, 18.1) g·m-2·h-1, between which the difference was not statistically significant (t=0.44, P>0.05). After keloid repair surgery, the thickness of epidermis in the keloids of 5 patients was (194±44) μm, which was significantly thicker than that of the normal skin (44±11) μm, (t=6.88, P<0.01). Furthermore, increased keratinocytes, lack of normal epidermal ridge structures, and thickened stratum corneum were observed in the keloid area. After keloid repair surgery, the expression level of cytokeratin-10 in keloids was significantly lower than that in normal skin of 3 patients (t=8.50, P<0.01), but there were no statistically significant differences in the expression levels of involucrin or filaggrin between keloids and normal skin (with t values of 0.07 and 0.96, respectively, P>0.05). Conclusions: Keloid tissue from patients with keloids displays increased number of keratinocytes and thickened epidermis. But the water barrier function in keloid area is similar to the surrounding normal skin, suggesting that TEWL may not be the main mechanism lead to the persistent development of keloids.


In vivo activities of aldose reductase inhibitors having a 1-(arylsulfonyl)hydantoin structure.
Two potent aldose reductase inhibitors, 1-[(2,5-dichlorophenyl)sulfonyl]hydantoin (Di-Cl-PSH) and 1-[beta-naphthyl)sulfonyl]hydantoin (beta-NSH), were tested for usefulness in the treatment of diabetic and galactosemic complications in animal experiments. Both drugs were effective for the treatment of diabetic neuropathy characterized by decreased motor nerve conduction velocity, that is, slowing of tail and sciatic-tibial motor nerve conduction velocities in streptozocin-induced diabetic rats was prevented during 3 weeks by intubating Di-Cl-PSH or beta-NSH at 50 mg/kg/day. Lenticular vacuole formation in rats fed a 30% galactose diet was blocked completely for at least 2 weeks by oral administration of Di-Cl-PSH or beta-NSH at both 30 and 100 mg/kg/day, whereas all of the eyes of vehicle-treated rats showed vacuole formation by day 4 on the galactose diet. The ED50 values of Di-Cl-PSH and beta-NSH for inhibition of sorbitol accumulation in the sciatic nerve and lens of streptozocin-induced diabetic rats were also estimated; the values of Di-Cl-PSH and beta-NSH were 1.1 and 3.4 mg/kg/day, respectively, for inhibition in the sciatic nerve and 4.8 and 16.0 mg/kg/day, respectively, for that in the lens. This study indicates that Di-Cl-PSH and beta-NSH have high potential for future clinical use as aldose reductase inhibitors.


Interpretation of the electron spin resonance spectra of nitroxide-maleimide-labelled proteins and the use of this technique in the study of albumin and biomembranes.
The composite ESR spectra of nitroxide-maleimide spin-labelled albumin and mitochondrial membranes were investigated. It was found that the mobile spectrum (so called "weakly immobilized") is due to the probe free in solution; it could be removed by dialysis, by lowering the ratio of spin label to albumin or by using acid pH values. Similar degrees of mobility were noted with spectra of spin label in solutions with viscosities similar to that of albumin. The immobile spectrum (so called "strongly immobilized") is due to the binding of N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)-maleimide to the proteins. Studies with modified albumins have shown that in this binding the free SH and amino groups are involved, but the three-dimensional structure offering conditions for hydrophobic binding is also required. The spectral parameters useful for evaluating conformational changes of proteins and an application to mitochondrial membranes are described.


Serum concentrations of opioids when comparing two switching strategies to methadone for cancer pain.
Our aim was to compare pharmacological aspects of two switching strategies from morphine/oxycodone to methadone; the stop and go (SAG) strategy in which methadone is started directly after the initial opioid has been stopped, and the 3-days switch (3DS), in which morphine/oxycodone is gradually changed to methadone by cross-tapering over 3 days. Forty-two cancer patients with pain and/or opioid side effects were assessed in this randomised trial. Trough serum concentrations of methadone, morphine, morphine-6-glucuronide (M6G), and oxycodone were measured on days 1, 2, 3, 4, 7, and 14. Primary outcome was number of patients with methadone concentrations in apparent C(SS) on day 4. Secondary outcomes were exposure to opioids during the first 3 days, interindividual variation of opioid concentrations, and correlation between methadone concentrations and pain intensity (PI) day 3. Thirty-five patients received methadone (16 in the SAG group, 19 in the 3DS group). The median preswitch morphine equivalent doses were 620 (range 350-2000) mg/day in the SAG group and 800 (range 90-3600) mg/day in the 3DS group (p = 0.43);42% reached C(SS) for methadone in the SAG group on day 4 compared with 22% in the 3DS group (p = 0.42). The SAG group was significantly less exposed to morphine/M6G/oxycodone and significantly more exposed to methadone in the first 3 days. Methadone showed a low correlation with PI. More patients dropped out after intervention in the SAG group than in the 3DS group (38% vs. 5%; p = 0.032). One SAG patient suffered from respiratory depression on day 5. The SAG group was initially more exposed to methadone and less to the replaced opioids but without observed clinical benefit and with a higher dropout rate. Patients switched to methadone should be followed closely for the first 5 days, regardless of switching strategy.