[Features of the pathogenesis and clinical picture of alcoholism developing against a background of pulmonary tuberculosis].
The paper deals with the clinical peculiarities and common characteristics of the formation and pathogenesis of the main symptoms of alcoholism in individuals with and without lung tuberculosis. The conducted clinical study suggests that the pathoplastic pathogenetic effect of lung tuberculosis results in an accelerated development of the main symptoms of alcoholism and is responsible for polymorphism of the clinical picture including the atypical symptomatology.


Catalytic biomineralization of fluorescent calcite by the thermophilic bacterium Geobacillus thermoglucosidasius.
The thermophilic Geobacillus bacterium catalyzed the formation of 100-μm hexagonal crystals at 60°C in a hydrogel containing sodium acetate, calcium chloride, and magnesium sulfate. Under fluorescence microscopy, crystals fluoresced upon excitation at 365 ± 5, 480 ± 20, or 545 ± 15 nm. X-ray diffraction indicated that the crystals were magnesium-calcite in calcite-type calcium carbonate.


The molecular genetics of post-transplantation lymphoproliferative disorders.
The post-transplantation lymphoproliferative disorders represent a significant clinical and diagnostic problem. However, these disorders also represent an important biological model for studying the development and progression of lymphoid neoplasia in immune deficiency. Accurate diagnosis and classification of these disorders requires correlative multiparametric analysis of the clinical behavior of the patient with the histopathological features, immunophenotype, clonal composition, and genetic alterations of the lymphoproliferative disorder. Such analyses should also assist in furthering our understanding of the pathogenesis of these disorders.


Identification of acyl protein thioesterases 1 and 2 as the cellular targets of the Ras-signaling modulators palmostatin B and M.
Finding the target: activity-based proteomic profiling probes based on the depalmitoylation inhibitors palmostatin B and M have been synthesized and were found to target acyl protein thioesterase 1 (APT1) and 2 (APT2) in cells.


[Gynecologic geriatric surgery at the University Gynecological Clinic Rostock during 1960--1974].
There is reported about 2279 gynaecological operations at women, aged 60 years and more, in a period from 1960 to 1974, divided into three 5-years-groups. The part of geriatric operations increased from 5,3% to 7,0% of all operations. The division into high risk-groups took place after points given by Loskant. 41,1% of all patients where classified into group III. Group IV has the highest postoperative mortality rate (5,3%). The postoperative mortality rate altogether was 2,2%. In the years from 1960 to 1974 it decreased from 2,6% to 1,9%. 25,1% of the surgical operations where carried out abdominaly. The high part of vaginal operations comes off by placing curettages into the analysis. Under that aspect must be seen the postoperative mortality rate 7,1% at abdominal and 0,7% at vaginal operations. In the main point indications for operation were malignant tumours (37,3%), haemorrhages (25,4%), benign tumours (17,6%), and position variations of the genitals (10,6%).


Quantitative testing of handgrip strength, myotonia, and fatigue in myotonic dystrophy.
An electrically calibrated, isometric hand dynamometer was used to quantitate maximum voluntary contraction (MVC(, relaxation time and fatigue time (at 50% MVC) in 18 normal and 10 myotonic dystrophy subjects. Precise measurements of MVC and fatigue time were obtained in normals and myotonic dystrophy patients. Relaxation times were markedly prolonged and were quite variable in all patients with myotonic dystrophy in contrast to the highly reproducible times in normals. Neither "warm-up" activity nor acetazolamide treatment altered relaxation time.


Quality Parameters of Wheat Bread with the Addition of Untreated Cheese Whey.
Τhe present study was carried out to evaluate wheat bread of three different flour compositions prepared by replacing water with untreated cheese whey (WCB). Bread prepared with water was taken as the control (CB). All breads were stored at 24 ± 1 °C for up to 6 days. Microbiological, physicochemical, and sensory analyses were determined as a function of storage time. WCB had lower total viable counts (TVC) (3.81 log cfu/g for CB and 2.78 log cfu/g for WCB on day 2 of storage) and showed delayed mold growth by 1 day (day 4 for CB and day 5 for WCB). WCB also had lower pH (5.91 for CB and 5.71 for WCB on day 0), higher titratable acidity values (TTA) (2.5-5.2 mL NaOH/10 g for CB and 4.5-6.8 mL NaOH/ 10 g for WCB), and higher protein content (PC) (PC 7.68% for CB and 8.88% for WCB). WCB was characterized by a more intense flavor, reduced hardness but similar cohesiveness, springiness, and adhesiveness compared to CB. Based primarily on sensory (appearance/mold formation) data, the shelf life of WCB was 4-5 days compared to 3-4 days for CB stored at 24 ± 1 °C. The proposed use of whey in bread preparation contributes decisively to the environmentally friendly management of whey.


Diagnosis of the right atrial myxoma after treatment of COVID-19: A case report.
Atrial myxoma is a rare disease but has a broad clinical presentation and complication that involves several systems- heart, lungs, brain, and systemic. An interdisciplinary approach is very important to optimize the outcome in patients with atrial myxomas. A thorough examination by primary care providers is crucial. Then radiologists or cardiologists can help with imaging modalities that can help diagnose and characterize the tumor. Prior to surgical resection by cardiothoracic surgeons, patients need to be evaluated by pulmonologists, cardiologists, and anesthesiologists for preoperative risk stratifications. In patients with neurological complications, pulmonary complications, or infectious endocarditis, input from neurologists, hematologists, infectious disease specialists is essential for patient care. In case antiplatelet/anticoagulation therapy or antibiotic treatment is warranted, pharmacists can provide valuable recommendations. Myxoma is the most common benign cardiac primary tumor, occurring in the right atrium in only 15%-20% of cases. This disease is asymptomatic initially depending upon size of the tumor, and symptoms develop as the tumor spreads. Atrial myxomas are associated with a triad of complications, including obstruction, emboli, and constitutional symptoms (such as fever and weight loss). This regard, embolization of the pulmonary circulation system is a complication of right myxoma. The patient was a 40-year-old male who presented to the emergency department complaining of fever and confusion. He had been previously hospitalized due to COVID-19 and treated with Remdesivir and plasmapheresis. He had tachycardia, tachypnea, thrombocytopenia, and increased liver enzymes. Chest imaging showed nodular lesions with necrotic areas and cavitary lesions in both lungs and the right atrium infected clot was seen in echocardiography. He was treated with intravenous antibiotics and finally underwent heart surgery due to the diagnosis of pulmonary septic embolism. The patient was finally diagnosed with right atrial myxoma according to heart mass histopathology. It is worth noting that the patient's thrombosis had already developed on the right atrial myxoma, which delayed the diagnosis in this patient. This thrombus formation was due to the hypercoagulability state of COVID-19 and following the insertion of a central venous catheter to perform plasmapheresis as a complication of treatment. Special attention should be paid to thromboprophylaxis and the early diagnosis of intravascular and intracardiac thrombosis in COVID-19 patients. Furthermore, the use of imaging modalities is recommended to differentiate thrombus from myxoma.


[Clinical features and survival analysis of patients with CD56 expression in de- novo acute myeloid leukemia with t(8;21)].
To explore the clinical features and survival of patients with CD56 expression in de- novo acute myeloid leukemia(AML)with t(8;21). . Clinical data of 82 de novo AML with t(8;21)who were newly diagnosed from Jan 2008 to Apr 2014 were analyzed retrospectively, 50 expressed CD56 and 32 not. Clinical characteristics and prognoses were compared between patients expressing and nonexpressing CD56. There were no statistically significant differences in terms of age, gender, white blood cell count(WBC), percentage of bone marrow blasts, extramedullary infiltration rate, the early mortality or the presence of additional cytogenetic abnormalities between CD56 + and CD56- groups(P>0.05). The expressions of lymphatic antigens CD19 between CD56 + and CD56- groups showed significant difference (30.0% vs 53.1% , P=0.036). The complete remission and 3-year overall survival(OS)showed no significant differences between CD56+ and CD56-groups, while 3- year disease- free survival(DFS)showed significant differences(25.8% vs 46.9%, P=0.014). Multivariable analysis for DFS identified CD56 positivity as an independent predictor. DFS of who received allogeneic hematopoietic stem cell transplantation(HSCT)was better than those treated with intermediate- dose cytarabine/high dose cytarabine(IDAC)as postremission therapy. The expression of CD56 in de-novo AML with t(8;21) appeared to be associated with poorer prognosis.


Gap junctions among the perikarya, dendrites, and axon terminals of the luminosity-type horizontal cell of the turtle retina.
Gap junctions of the H1 horizontal cell of the turtle retina (Leeper, '78) were studied in thin-sectioned material and in freeze-fracture replicas. Perikaryal gap junctions were extremely restricted, 0.02-0.07 micron2 in in area, whereas those of axon terminals were much larger, most being 0.1-1.0 micron2. Both varieties, however, had the usual seven-layered appearance in thin section and measured 15 +/- 1 nm in overall width between cytoplasmic faces. Freeze-fractured views of the perikaryal junctions revealed roughly circular patches of P-face 9-nm particles and E-face pits. The axon terminal gap junctions were seen as large areas of P-face particles and E-face pits containing occasional islands of unspecialized membrane. Particle densities varied from 1,455 to 2,448 microns-2. A serial reconstruction was made of a portion of the axon terminal network in order to measure the surface areas of the axons contained therein and the fraction occupied by gap junctions. These data demonstrated that the fractional area occupied by gap junctions was roughly in inverse proportion to the area of the axon region (tuberous core vs. terminal process). It is argued that this constitutes an impedance matching device to ensure adequate current flow through the axon processes. Assuming that each P-face particle represents a connection having a conductance of 10(-10) S and given the P-face particle density and gap junctional areas determined in this report, we calculated that the gap junction distribution is adequate to account for the spatial properties of the horizontal cell axon network (Lamb, '76).


Surgical treatment of adult scoliosis: is anterior apical release and fusion necessary for the lumbar curve?
A retrospective study. To analyze radiographic and functional outcomes after posterior segmental spinal instrumentation and fusion (PSSIF) with and without an anterior apical release of the lumbar curve in adult scoliosis patients. No comparison study on PSSIF of adult lumbar scoliosis with apical release versus without has been published. Forty-eight adult patients with lumbar scoliosis (average age at surgery 49.6 years, average follow-up 3.7 years) who underwent PSSIF were analyzed with respect to radiographic change, perioperative and postoperative complications, and Scoliosis Research Society (SRS) outcome scores. Twenty-three patients underwent an anterior apical release of the lumbar curve via a thoracoabdominal approach followed by PSSIF (Group I). The remaining 25 patients underwent a PSSIF of the lumbar curve followed by anterior column support at the lumbosacral region through an anterior paramedian retroperitoneal or posterior transforaminal approach (Group II). Before surgery, Group I showed a somewhat larger lumbar major Cobb angle (63.2 degrees vs. 55.9 degrees , P = 0.07), and both groups demonstrated significant differences in lumbar curve flexibility (26.9% vs. 37.2%, P = 0.02) and thoracolumbar kyphosis (27.0 degrees vs. 15.0 degrees , P = 0.03). After surgery, at the ultimate follow-up, there were no significant differences in major Cobb angle, C7 plumbline to the center sacral vertical line (P = 0.17), C7 plumbline to the posterior superior endplate of S1 (P = 0.44), and sagittal Cobb angles at the proximal junction (P = 0.57), T10-L2 (P = 0.24) and T12-S1 (P = 0.51). There were 4 pseudarthroses in Group I and one in Group II (P = 0.02). Postoperative total normalized SRS outcome scores at ultimate follow-up were significantly higher in Group II (69% vs. 79%, P = 0.01). Posterior segmental spinal instrumentation and fusion without anterior apical release of lumbar curves in adult scoliosis demonstrated better total SRS outcome scores and no differences in radiographic parameters without differences in clinical complications. However, the use of BMP in some of these patients (44%) may have also contributed to these differences.


Does epidermal growth factor participate in the regulation of glucose, insulin and glucagon levels?
The presence of receptors for epidermal growth factor (EGF) on beta cells in the rat pancreatic islets has been established, but the physiological role remains to be settled. The aim of the present study was to evaluate the effect of EGF on glucose homeostasis. Fasted rats were treated with intraperitoneal injections of 10, 40 or 80 microg/kg body weight, either with EGF or 1% bovine serum albumin (controls). In a second experiment, fasted rats received an intraperitoneal injection of 1 mg glucose/kg body weight, followed by an injection of EGF or bovine serum albumin. Blood was drawn before the injections and at different time points afterwards. The plasma concentrations of glucose, insulin and glucagon were measured. A modest elevation of the concentrations of glucose and insulin in plasma during the study was found in fasted rats in experiment 1. The increase in insulin concentration was attenuated by EGF, but after glucose injection this effect was reversed. Plasma glucagon levels were dose-dependently elevated by EGF and increased instead of decreased after glucose injection. Our data suggest that EGF might play an important role in the regulation of glucagon secretion by preventing the lowering effect of glucose on plasma glucagon levels.


Psychological aspects of diabetes mellitus.
Diabetes mellitus (DM) presents itself in two forms: insulin-dependent (type 1 DM) and non-insulin-dependent (type 2 DM). Although type 2 DM usually has an adult onset, in recent years there has been a significant rise in the number of children diagnosed with type 2 DM in the United States. Reasons for this increased frequency are believed to be a larger percentage of children who are overweight, a family history of diabetes, and a considerable increase in the use of psychotropic medication in children. The diagnosis of DM is a significant stressor not only for patients but also for their environment. Children with DM are sometimes stigmatized by their peers and relatives who do not understand the illness or are frightened by it. Some children also may need to alter several of their customary routines and are often scared to participate in activities in which they were previously engaged. The family's response to the diagnosis of DM may have a negative effect on glycemic control. Differences have been found in the way patients with type 1 DM and type 2 DM cope with and adapt to their diagnosis.


Case Report: The risks associated with chronic theophylline therapy and measures designed to improve monitoring and management.
Symptoms of theophylline toxicity and factors that augment the risk of developing it are well documented in the literature. However these appear to be poorly considered in clinical practice. This case underlines the challenges in recognising and managing theophylline toxicity; moreover the requirement for improved application of knowledge of its pharmacokinetics to our practice. In this case we observe how theophylline toxicity can be overlooked due to the presence of non-specific symptoms and lack of a structured system to mitigate error in detection, in both hospital medicine and general practice. Here, the initial theophylline concentration measurement was documented as 59.3 mg/l in a patient taking the medication long-term, with the previous concentration being recorded one year prior. Management consisted of suspension of theophylline along with best supportive care, however in the process other conditions were exacerbated and the patient ultimately died in hospital. Congestive cardiac failure, congestive liver disease and polypharmacy were factors isolated from this case that expedited the patients' development of theophylline toxicity. This was perpetuated by delay in diagnosis due to presentation with generalised symptoms including tachycardia, vomiting and neurological symptoms. Findings from this case necessitate a requirement for more stringent monitoring of theophylline when taken chronically in those who demonstrate risk factors for toxicity. This would aim to prevent accumulation of the drug, toxicity onset and subsequent acute presentation to hospital. Intervention, through charcoal haemoperfusion may provide a means of enhanced recovery to reduce sequelae of toxicity.


Presence and type of oncogenic human papillomavirus in classic and in differentiated vulvar intraepithelial neoplasia and keratinizing vulvar squamous cell carcinoma.
The presence and type of oncogenic papillomavirus (HPV) in classic warty/basaloid vulvar intraepithelial neoplasia and in differentiated vulvar intraepithelial neoplasia and keratinizing vulvar squamous cell carcinoma was investigated using three techniques, that is, histology, in situ hybridization, and PCR-ELISA. HPV typing was performed using in situ hybridization and PCR-ELISA. Differentiated vulvar intraepithelial neoplasia and invasive keratinizing vulvar squamous cell carcinoma proved completely negative for HPV by PCR-ELISA, in situ hybridization, and histologic examination, while in classic vulvar intraepithelial neoplasia, a HPV positivity of 66.1% was found. HPV 16 was the predominant type, with HPV 35, 33, and 52 types found rarely and sometimes together with HPV 16. PCR-ELISA proved to be the most suitable method to detect and type mucosal oncogenic HPVs. The absolute absence of HPV DNA in differentiated vulvar intraepithelial neoplasias and in keratinizing vulvar squamous cell carcinoma suggests a strong HPV-independent pathway of malignant progression to invasive carcinoma.


Transthoracic 2D echocardiographic guidance for percutaneous removal of a nonopaque intracardiac catheter fragment.
A radiolucent fragment of a fractured central venous catheter embolized to the right heart resulting in life-threatening dysrhythmias in a middle-aged male patient who had undergone orthotopic liver transplantation 1 day earlier. The fragment was removed via the right transjugular route using sonographic guidance to entrap the fragment with a brightly echogenic snare. The technique described protects the caval anastomoses in the liver transplant recipient and overcomes the limitation of fluoroscopy in removing radiolucent bodies.


Attitude and awareness of medical and dental students towards collaboration between medical and dental practice in Hong Kong.
Medical-dental collaboration is essential for improving resource efficiency and standards of care. However, few studies have been conducted on it. This study aimed to investigate the attitude and awareness of medical and dental students about collaboration between medical and dental practices in Hong Kong. All medical and dental students in Hong Kong were invited to complete a questionnaire survey at their universities, hospitals and residential halls. It contained 8 questions designed to elicit their attitudes about the collaboration between medical and dental practice. Students were also asked about their awareness of the collaboration between dentistry and medicine. The questionnaires were directly distributed to medical and dental students. The finished questionnaires were immediately collected by research assistants on site. A total of 1,857 questionnaires were distributed and 809 (44%) were returned. Their mean attitude score (SD) towards medical-dental collaboration was 6.37 (1.44). Most students (77%) were aware of the collaboration between medical and dental practice in Hong Kong. They considered that Ear, Nose & Throat, General Surgery and Family Medicine were the 3 most common medical disciplines which entailed collaboration between medical and dental practice. In this study, the medical and dental students in general demonstrated a good attitude and awareness of the collaboration between medical and dental practice in Hong Kong. This established an essential foundation for fostering medical-dental collaboration, which is vital to improving resource efficiency and standards of care.


Canadian permafrost stores large pools of ammonium and optically distinct dissolved organic matter.
Permafrost degradation may lead to mobilization of carbon and nutrients and enhance microbial processing rates of previously frozen organic matter. Although the pool size and chemical composition of dissolved organic matter (DOM) are fundamental determinants of the carbon cycle in Arctic watersheds, its source within the seasonally thawing active layer and the underlying permafrost remains largely uncharacterized. Here, we used 25 soil cores that extended down into the permafrost from nine sites across Arctic Canada to quantify dissolved organic carbon (DOC) and nitrogen stocks, and to characterize DOM optical properties. Organic permafrost stores 5-7 times more DOC and ammonium than the active layer and mineral permafrost. Furthermore, the permafrost layers contain substantial low molecular weight DOM with low aromaticity suggesting high biodegradability. We conclude that soil organic matter stoichiometry and cryogenic processes determine permafrost DOM chemistry, and that thawing will mobilize large amounts of labile DOC and ammonium into Arctic watersheds.


Possible liver cell differentiation in testicular germ cell tumours.
Germ cell tumours may imitate various structures of the developing embryo and foetus. Certain structures have, however, very rarely or never been observed in these tumours. Thus the presence of hepatic tissue in testicular germ cell tumours has not been reported. In a series of 37 non-seminomatous testicular tumours seven tumours contained epithelial structures showing morphological and functional resemblance to liver cell trabeculae. These structures were present in tumours with yolk sac tumour (YST) components and most of the tumours also contained teratoid elements. With the immunoperoxidase technique the epithelial structures were heavily stained for alpha-foetoprotein (AFP) and ferritin in all cases, while positive staining for albumin, prealbumin and transferrin was occasionally found. Alpha-I-antitrypsin and haemoglobin F were demonstrated in few scattered cells. Whether or not these epithelial structures should be included among the various patterns of YST or considered to be teratoid components is uncertain. It is suggested that examinations of the heterogeneity of the concomitant serologic AFP may support one or other assumption.


Prophylactic antibiotics reduce morbidity due to septicemia during intensive treatment for pediatric acute myeloid leukemia.
The aim of this study was to determine whether antibiotic prophylaxis during periods of neutropenia reduced streptococcal (S. viridans) sepsis and overall bacterial sepsis. The authors reviewed outcomes of 78 evaluable patients who were consecutively treated for acute myeloid leukemia (AML) from October 2002 through January 2007. Several successive prophylactic antibiotic regimens were used. All patients received antifungal prophylaxis with oral voriconazole. Oral cephalosporins did not significantly reduce the odds of bacterial sepsis (P = .81) or streptococcal (S. viridans) sepsis (P = .90) relative to no prophylaxis. Intravenous (iv) cefepime completely prevented streptococcal (S. viridans) sepsis and reduced the odds of bacterial sepsis 91% (P < .0001) relative to no prophylaxis, but resistant gram-negative bacteria emerged in 2 patients. Vancomycin with oral ciprofloxacin or a cephalosporin reduced the odds of bacterial sepsis by 93% (P < .0001) and streptococcal (S. viridans) sepsis by 99% (P < .0001). The fungal infection rate did not differ significantly between patients who did and did not receive antibiotic prophylaxis (1.0 per 1000 patient-days for both groups). The observed reduction in average hospital days per chemotherapy course for patients given vancomycin regimens or cefepime was 5.7 (P < .0001) and 4.1 (P = .0039) days, respectively. No reduction was observed with oral cephalosporins (P = .10). Furthermore, vancomycin regimens or cefepime were associated with a 20% reduction in healthcare charges (P = .0015) relative to using no antibiotics. One patient, who was on oral cefuroxime alone, died of septicemia. Prophylaxis with intravenous cefepime or a vancomycin regimen, and voriconazole, reduced morbidity in children with AML, and resulted in dramatic decreases in the incidence of septicemia and hospitalization days.


Tick-borne viral encephalitis in Finland. The clinical features of Kumlinge disease during 1959-1987.
During 1959-1987, 126 patients in Aland Islands and main Finland had serologically verified infections with the virus of tick-borne encephalitis (Kumlinge disease). The most useful test for specific virological diagnosis was haemagglutination inhibition-IgM (HI-IgM). Most cases were from Aland Islands and nearby south-western main Finland. Two of the infections were imported. There were three laboratory infections and two transfusion infections. The disease occurred mainly from July to September. Detailed hospital records of 108 of the patients could be obtained. Ninety-five per cent of the patients had headaches, 82% had lymphocytosis of the cerebrospinal fluid, and 81% had high fever. Forty-four per cent had a confirmed biphasic course of disease. Seventeen per cent were severely ill. There were no deaths. The sequels were psychic irritability and fatigue for up to 1 year. There were eight cases of paresis, two of which became permanent.


A new form of amyloid protein associated with chronic hemodialysis was identified as beta 2-microglobulin.
Amyloid fibrils were isolated from amyloid-laden tissue obtained from a chronic hemodialysis patient with carpal tunnel syndrome. After solubilization in guanidine HCl, a significant amount of the protein was located in a homogeneous low molecular weight fraction. The protein was found to be identical to beta 2-microglobulin, with regard to its molecular weight of 11,000, amino acid composition and 16 amino-terminal amino acids: Ile-Gln-Arg-Thr-Pro-Lys-Ile-Gln-Val-Tyr-Ser-Arg-His-Pro-Ala-Glu-. These results demonstrate that the amyloid associated with chronic hemodialysis contains as major component a new form of amyloid fibril protein that is homologous to beta 2-microglobulin.


[Late results of different methods of surgical treatment of experimental retropatellar cartilage defects].
The result of the experimental studies encouraged us to treat our patients with chondro-malacia patellae not only by superficially rasping the damaged cartilage, but also by drilling several holes down to the subchondral layer. This allows a type of tissue repair by connective tissue. In addition we prefer a section of the retinacula and an anteposition of the patella ligament.


Is there any bona fide example of O-H...F-C bond in solution? The cases of HOC(CF3)2(4-X-2,6-C6H2(CF3)2) (X = Si(i-Pr)3, CF3).
The reinvestigation of the title compounds, which are the only examples reported to show experimentally (by NMR) O-H...F-C bonds in solution proves that the NMR data were misinterpreted and the restrictions to rotation of one CF(3) group are due to crowding, not to intramolecular O-H...F-C bond.


Dealing with neonatal emergencies in low-resource settings.
We describe the development and delivery of neonatal care including trends and impacts of major interventions on neonatal mortality particularly in low-resource settings. Low- and middle-income countries continue to be major contributors to neonatal mortality. Although there has been progress in reducing neonatal mortality, neonatal deaths are contributing an increasing percentage of childhood mortality. Several interventions targeting neonatal care such as neonatal resuscitation and essential newborn care have contributed to improved outcomes. However, there are still many neonatal deaths that are preventable with known effective interventions. This review addresses interventions proven effective in reducing neonatal mortality, challenges to implement them, and future directions of implementing these interventions in low- and middle-income countries.


Skin granulomas due to Mycobacterium gordonae.
A 38-year-old woman presented with small, ulcerated, red or bluish nodules on the right hand, clinically resembling mycobacterial granulomas; these appeared a few months after a bite by a rat, while the patient was collecting frogs in a pond in the Belgian Ardennes. The histopathologic picture was compatible with a diagnosis of mycobacterial infection and rare acid-fast bacilli could be found. Repeated bacteriologic investigations were performed and these led to the identification of a strain displaying characteristics of Mycobacterium gordonae. The skin condition responded well to rifampicin (300 mg/day) within 6 months.


Mitochondrial thioredoxin-2 from Manila clam (Ruditapes philippinarum) is a potent antioxidant enzyme involved in antibacterial response.
Thioredoxin (TRx) is a ubiquitous protein involved in the regulation of multiple biological processes. The TRx-2 isoform is exclusively expressed in mitochondria, where it contributes to mitochondrial redox state maintenance. In the present study, a novel thioredoxin-2 gene was identified in the Manila clam, Ruditapes philippinarum. The full-length sequence of RpTRx-2 (1561 bp) consists of a 498 bp coding region encoding a 166 amino acid protein. The N-terminal region of RpTRx-2 harbors a mitochondrial localization signal (56 amino acids), while the C-terminal portion contains the characteristic (89)WCGPC(93) catalytic active site. Phylogenetic analysis revealed that RpTRx-2 is closest to its ortholog from abalone. The broad distribution pattern of RpTRx-2 mRNA in healthy animal tissues implicates a generally significant function in normal clam physiology. The transcription level of RpTRx-2, however, is highest in hemocytes. Lipopolysaccharide and Vibrio tapetis bacterium caused up-regulation of the RpTrx-2 transcript levels in gill and hemocytes. Interestingly, clam manganese superoxide dismutase (MnSOD) mRNA levels in hemocytes elicited a corresponding response to these immune challenges. RpTRx-2 was recombinantly expressed in Escherichia coli BL21 (DE3) and used in insulin disulfide reduction assay as well as metal-catalyzed oxidation assay to elucidate its antioxidant property by reducing substrate and protecting super-coiled DNA from oxidative damage through free radical scavenging, respectively. Collectively, our data indicated that RpTRx-2, a mitochondrial TRx-2 family member, is an antioxidant enzyme that may be involved in antibacterial defense of clams.


Chemical synthesis of a pentaribonucleoside tetraphosphate constituting the 3'-acceptor stem sequence of E. coli tRNAIle using 2'-O-(3-methoxy-1,5-dicarbomethoxypentan-3-yl)-ribonucleoside building blocks. Application of a new achiral and acid-labile 2'-hydroxyl protecting group in tRNA synthesis.
A synthesis of a pentaribonucleotide fragment constituting the residues 59-63 of 3'-terminus of E. coli tRNAIle, 5'-ApGpUpCpC-3', has been carried out using a new, easily accessible and achiral 2'-ketal protecting group. The new 2'-ketal group has an additional advantage in that it is easily functionalized to the diamide with aqueous ammonia in the penultimate step of deblocking of fully protected oligoribonucleotides. Such a functionalization of the 2'-ketal group at the penultimate step of deblocking of the fully protected tRNA molecule enhances its relative rate of removal under an acidic condition with a minimum of damage of the target tRNA molecule.


Determinants of protein elution rates from preparative ion-exchange adsorbents.
The rate processes involved in elution in preparative chromatography can affect both peak resolution and hence selectivity as well as practical factors such as facility fit. These processes depend on the physical structure of the adsorbent particles, the amount of bound solute, the solution conditions for operation or some combination of these factors. Ion-exchange adsorbents modified with covalently attached or grafted polymer layers have become widely used in preparative chromatography. Their often easily accessible microstructures offer substantial binding capacities for biomolecules, but elution has sometimes been observed to be undesirably slow. In order to determine which physicochemical phenomena control elution behavior, commercially available cellulosic, dextran-grafted and unmodified agarose materials were characterized here by their elution profiles at various conditions, including different degrees of loading. Elution data were analyzed under the assumption of purely diffusion-limited control, including the role of pore structure properties such as porosity and tortuosity. In general, effective elution rates decreased with the reduction of accessible pore volume, but differences among different proteins indicated the roles of additional factors. Additional measurements and analysis, including the use of confocal laser scanning microscopy to observe elution within single chromatographic particles, indicated the importance of protein association within the particle during elution. The use of protein stabilizing agents was explored in systems presenting atypical elution behavior, and l-arginine and disaccharide excipients were shown to alleviate the effects for one protein, lysozyme, in the presence of sodium chloride. Incorporation of these excipients into eluent buffer gave rise to faster elution and significantly lower pool volumes in elution from polymer-modified adsorbents.


On the Absolutely Continuous Spectrum of Generalized Indefinite Strings.
We investigate absolutely continuous spectrum of generalized indefinite strings. By following an approach of Deift and Killip, we establish stability of the absolutely continuous spectra of two model examples of generalized indefinite strings under rather wide perturbations. In particular, one of these results allows us to prove that the absolutely continuous spectrum of the isospectral problem associated with the conservative Camassa-Holm flow in the dispersive regime is essentially supported on the interval [ 1 / 4 , ∞ ) .


Factors influencing the deposition of hydroxyapatite coating onto hollow glass microspheres.
Hydroxyapatite (HA) and HA coated microcarriers for cell culture and delivery have attracted more attention recently, owing to the rapid progress in the field of tissue engineering. In this research, a dense and uniform HA coating with the thickness of about 2 μm was successfully deposited on hollow glass microspheres (HGM) by biomimetic process. The influences of SBF concentration, immersion time, solid/liquid ratio and activation of HGM on the deposition rate and coating characteristics were discussed. X-ray diffraction (XRD) and Fourier transform infrared spectrum (FTIR) analyses revealed that the deposited HA is poorly crystalline. The thickness of HA coating showed almost no increase after immersion in 1.5SBF for more than 15 days with the solid/liquid ratio of 1:150. At the same time, SBF concentration, solid/liquid ratio and activation treatment played vital roles in the formation of HA coating on HGM. This poorly crystallized HA coated HGM could have potential use as microcarrier for cell culture.


Hippocampal volume is an independent predictor of cognitive performance in CADASIL.
Recent evidence suggests that hippocampal changes are present in vascular cognitive impairment but their importance and relationship with ischaemic mechanisms remain controversial. To investigate these issues we performed MRI and cognitive assessment in a large cohort (n=144) of patients with CADASIL, a hereditary small vessel disease and model of pure vascular cognitive impairment. Dementia status was ascribed according to DSM-IV and global cognitive function assessed with the Minimental State Examination (MMSE) and Mattis Dementia Rating Scale (MDRS). Hippocampal volume (HV) correlated with age (r=-0.33, p<0.001), brain volume (r=0.39, p<0.001) and lacunar lesion volume (r=-0.23, p=0.008), but not white matter lesions or microhaemorrhages. HV was reduced in dementia (2272+/-333 mm(3) versus 2642+/-349 mm(3), p<0.001) in the whole cohort and the subgroup progressing to dementia before age 60. HV correlated with MMSE (r=0.30, p<0.001), MDRS (r=0.40, p<0.001) and in a multivariate model predicted cognition independent of typical vascular lesions and whole brain atrophy. These findings strengthen the view that hippocampal atrophy is an important pathway of cognitive impairment in vascular as well as degenerative disease.


Integrated neural circuits of sleep and memory regulation in Drosophila.
Sleep and memory are highly intertwined, yet the integrative neural network of these two fundamental physiological behaviors remains poorly understood. Multiple cell types and structures of the Drosophila brain have been shown involved in the regulation of sleep and memory, and recent efforts are focusing on bridging them at molecular and circuit levels. Here, we briefly review 1) identified neurons as key nodes of olfactory-associative memory circuits involved in different memory processes; 2) how neurons of memory circuits participate in sleep regulation; and 3) other cell types and circuits besides the mushroom body in linking sleep and memory. We also attempt to provide the remaining gaps of circuitry integration of sleep and memory, which may spark some new thinking for future efforts.


[A combination of reoperation for pseudoaneurysm following the Cabrol procedure and total aortic arch replacement in a patient with Marfan syndrome--a case with an aberrant right subclavian artery].
A 44-year-old male with Marfan's syndrome had undergone an initial operation for DeBakey type I acute aortic dissection with annulo-aortic ectasia. He had undergone replacement of the ascending aorta and aortic valve with a composite graft and reconstruction of the coronary artery by the Cabrol procedure. At 5 years after the initial surgery he experienced chest pain and was subsequently examined. Computed tomography revealed a pseudoaneurysm in the ascending aorta and the residual aortic dissection. The maximum diameter of the pseudoaneurysm was 85 mm and the maximum diameter of the aortic arch was 55 mm. The aortic arch was associated with an aberrant right subclavian artery. Angiography revealed that the pseudoaneurysm was caused by leakage at the coronary ostium-graft anastomoses. We repaired the anastomoses and performed total aortic arch replacement with reconstruction of four arch branches. The postoperative course was uneventful without any complications. We report this case because there have been few reports regarding arch replacement in cases with an aberrant right subclavian artery.


[Reconstruction of severe acetabular bone defects using Burch-Schneider cage].
The Burch-Schneider cages (BSC) are designed to manage severe acetabular defects by bridging large bone gaps and preventing medial and superior migration of the prosthetic cup. The purpose of the study was to evaluate the results of such revisions after prolonged follow-ups. From 1985 to 2000 sixty-nine acetabular revisions with BSC were performed in 68 patients with an acetabular defect classified as type Paprosky 3A (32) and 3B (37) at our institutions. After meticulous debridement of the entire acetabulum cancellous chips were pressurized into the bone defects to restore the hemispherical shape. The cage flange for the ischium was then placed after slight contouring into the foramen obturatum or inside the ischium. Finally, the cage was fixed against the ilium with at least three screws. The average age at the time of surgery was 67.9 years (range, 51-78), the mean follow-up equalled 8.3 years (range, 5-20), and the mean Harris hip score was 48 points (range, 29-76). A clinical follow-up study was performed with using conventional measures such as Harris hip score, x-ray analysis, strength of the abductor muscles, and ability to walk without support. A total of 55 patients (80.9 %) remained without any revision until the latest follow-up. Six components were removed due to aseptic loosening (8.7 %); five for septic loosening (7.2 %), and two revisions had to be performed for recurrent instability (2.9 %). Moreover, there were another six hips definitely or probably loose according to x-ray analysis resulting in a 17.4 % (12/69) rate of aseptic failure. Successful cage re-replacement was achieved only in two cases while the remaining nine hips ended as resection arthroplasties. At the time of follow-up examinations the average Harris hip score was 74 points (range, 51-91), only twelve patients were able to walk without support (12/68, 17.6 %), and insufficiency of the abductor muscles was found in fifteen hips (15/69, 21.7 %). Consolidation of the bone graft was observed in 79.7 % (55/69) of our hips. The severe acetabular bone defect reconstructions have been deteriorating with time as reported by most of the published studies. The results of the current study are no exception. On the other hand, the rate of complications observed in our study was comparable or even lower than in similar studies. Despite relatively worse results with prolonged follow-ups, the BSC remains a considerable part of the current orthopaedic armamentarium especially when extensive acetabular bone loss is countered. Loosening belongs to the most common complications of the BSC.


Secure attachment predicts lower societal cost amongst severely antisocial adolescents.
Social and economic costs associated with antisocial behaviour are well-established, but little is known about the potential costs savings/benefits of secure attachment in this high-risk group. We aimed to provide the first test of attachment quality as a distinct predictor of economic costs. 111 adolescents (10-17 years of age, M = 15.0, SD = 1.6; 71% male) referred to young offender services due to high levels of antisocial behaviour were included. Costs were measured by detailed service-use interview, and attachment security to mother and father elicited through the Child Attachment Interview. The level of antisocial behaviour and callous-unemotional traits were assessed. Cost predictors were calculated using generalised linear models. Mean 12-months service costs were £5,368 (sd 5,769) per adolescent, with justice system and educational service costs being the main components. After adjusting for covariates, economic costs were predicted by attachment quality to fathers, with a difference of £2,655 per year between those with secure (£3,338) versus insecure attachment (£5,993); significant cost effects were not found for attachment quality to mothers. Higher levels of callous-unemotional traits, lower verbal IQ, higher levels of antisocial behaviour, and older age were also significant cost predictors. Secure attachment to fathers is a predictor of reduced public cost in adolescents with severe antisocial behaviour. This novel finding for severely antisocial youth extends previous findings in less antisocial children and underscores the public health and policy benefits of good caregiving quality and the value of population-level dissemination of evidence-based interventions that improve caregiving quality.


Sprouting angiogenesis is regulated by shedding of the C-type lectin family 14, member A (CLEC14A) ectodomain, catalyzed by rhomboid-like 2 protein (RHBDL2).
C-type lectin family 14, member A (CLEC14A), is a single-pass transmembrane glycoprotein that is overexpressed in tumor endothelial cells, and it promotes sprouting angiogenesis and modulates endothelial function via interactions with extracellular matrix proteins. Here, we show that CLEC14A is cleaved by rhomboid-like protein 2 (RHBDL2), one of 3 catalytic mammalian rhomboid-like (RHBDL) proteases, but that it is not cleaved by RHBDL1 or -3. Site-directed mutagenesis identified the precise site at which RHBDL2 cleaves CLEC14A, and targeted, small interfering RNAs that knockdown endogenous CLEC14A and RHBDL2 in human endothelial cells validated the specificity of CLEC14A shedding by RHBDL2. Loss of endogenous cleaved CLEC14A increased endothelial migration 2-fold, whereas that addition of recombinant cleaved CLEC14A inhibited the sprouting of human and murine endothelial cells 3-fold in several in vitro models. We assessed the in vivo role of cleaved CLEC14A in angiogenesis by using the rodent subcutaneous sponge implant model, and we found that CLEC14A protein inhibited vascular density by >50%. Finally, we show that cleaved CLEC14A binds to sprouting endothelial tip cells. Our data show that the ectodomain of CLEC14A regulates sprouting angiogenesis and suggests a role for RHBDL2 in endothelial function.-Noy, P. J., Swain, R. K., Khan, K., Lodhia, P., Bicknell, R. Sprouting angiogenesis is regulated by shedding of the C-type lectin family 14, member A (CLEC14A) ectodomain, catalyzed by rhomboid-like 2 protein (RHBDL2).


Influence of the geographic proximity of city features on the spatial variation of urban carbon sinks: A case study on the Pearl River Delta.
Locations of city features, e.g., city centers, roads, railways, and rivers, may impact urban carbon sinks. Therefore, the effects of city features on spatial variations of urban carbon sinks were investigated using geographic proximity data. The main results were as follows. (1) Carbon sink function varied in a complex manner with distance from the city center and with city size. The carbon sink per unit area increased with distance from the prefecture-level city center (0-30 km), with the dominant influence occurring within a 9 km radius. The lowest carbon sink per unit area was observed at a distance of 12 km from the city center of the provincial capital city (Guangzhou) and special economic zone (Shenzhen), which may be suburban industrial zones. (2) Carbon sinks decreased with increases in road grades as a result of the different functions and traffic flow, and carbon sinks were lowest near city express ways. For highways, carbon sinks were lower near highway entrances and exits. Carbon sinks around ordinary railways were higher than those around subways and light rail, but carbon sink characteristics grew more complex with increasing distances from subways and light rail. (3) Rivers were closely related to the urban layout. Grade I (i.e., larger) rivers were associated with lower carbon sinks, and carbon sink characteristics became increasingly complex around larger rivers. Within a 0-1000 m distance of all rivers, the carbon sink per unit area increased rapidly, but carbon sink characteristics differed slightly for grade I rivers. This study implies that it is important to take urbanization spatial position effects into account while assessing regional carbon sinks during urbanization and development.


Steroid analogs inhibit hormone binding by an extract from Nippostrongylus brasiliensis (Nematoda).
1. An extract from the rodent nematode Nippostrongylus brasiliensis contained putative receptors that bound radiolabeled sex hormones, based on isoelectric focusing. 2. Binding of radiolabeled testosterone by receptors at pH 4.4 was highly inhibited by the androgen analogs, testosterone-3-oxime and 4-aza-5-androsten-3-on-17 beta-ol. 3. Binding of radiolabeled progesterone by receptors at pH 6.4 was highly inhibited by the progesterone analogs 3,5-seco-4-norpregnan-5-on-3-oic acid and 19-norethisterone or 21-deoxycorticosterone. 4. Binding of radiolabeled 17 beta-estradiol by receptors at pH 4.9 was highly inhibited by epiandrosterone. 5. In vivo development of N. brasiliensis to the adult was partially inhibited by selected steroid analogs.


Clinical efficacy of zonisamide in Lennox-Gastaut syndrome: Korean multicentric experience.
To evaluate the efficacy and safety of zonisamide (ZNS) as long-term adjunctive therapy in children with Lennox-Gastaut syndrome (LGS). We evaluated the seizure frequency, cognitive outcomes, and side effects of 62 LGS patients maintained on ZNS for at least 12 months in three tertiary centers. Of the 62 LGS patients maintained on ZNS, 3 (4.8%) had 100% seizure control; 14 (22.6%) had >75% to <100% reduction in seizure frequency; 15 (24.2%) had >50% to <75% reduction in seizure frequency; 6 (9.7%) had >0% to <50% reduction in seizure frequency, and 24 (38.7%) had no seizure reduction. Seizure outcomes were not related to seizure types or etiologies. Adverse events included somnolence and anorexia, but all were transient and successfully managed by careful follow-up. Our results indicate that adjunctive treatment with ZNS is safe and effective in pediatric LGS patients.


Clinical outcome of generalized myasthenia gravis in Hong Kong Chinese.
Myasthenia gravis (MG) is an organ-specific autoimmune disease characterized by autoantibody-mediated impairment of skeletal muscle neuromuscular transmission. MG causes significant morbidity and even mortality. We studied the long-term clinical outcome of generalized MG (gMG) patients. Records of Chinese gMG patients managed in Queen Mary Hospital from 1997 to 2012 were reviewed. Clinical, serological and radiological characteristics were studied for independent predictors of good long-term clinical outcome. A total of 123 Chinese gMG patients were studied. Their mean onset age was 44.8 years (range 7-83 years), 87 (70.7%) were female, and median follow-up duration was 114 months (interquartile range 67-188 months). Thymoma were detected in 45 patients (36.6%). Acetylcholine receptor autoantibodies were detected in 99 patients (87.6%). Ninety-three patients (75.6%) received immunosuppressant therapy (corticosteroid 75.6%, azathioprine 58.5%, mycophenolate mofetil 5.7%, cyclosporin 5.7%) and 77 (62.6%) received thymectomy. Thirty-five (28.5%) patients experienced MG crisis and two died. Ninety-six (78.0%) patients had good outcome defined by Myasthenia Gravis Foundation of America (MGFA) post-intervention status (PIS) of complete stable remission (CSR), pharmacological remission (PR) or minimal manifestation (MM) at latest follow-up, whereas 24 patients (19.5%) had intermediate outcome defined by MGFA PIS of Improved (I); 3 patients (2.4%) had poor prognosis defined by MGFA PIS of unchanged (U), worse (W), exacerbation (E) or died of MG (D). Azathioprine therapy was the only independent predictor of good outcome (OR 3.57, 95% CI 1.05-12.10, p=0.042). 78.0% of gMG patients had good long-term clinical outcome. Azathioprine therapy independently predicted good clinical outcome.


A quantitative evaluation of cross-participant registration techniques for MRI studies of the medial temporal lobe.
Accurate cross-participant alignment within the medial temporal lobe (MTL) region is critical for fMRI studies of memory. However, traditional alignment approaches have been exceptionally poor at registering structures in this area due to significant inter-individual anatomic variability. In this study, we evaluated the performance of twelve registration approaches. Specifically, we extended several traditional approaches such as SPM's normalization and AFNI's 3dWarpDrive to improve the quality of alignment in the MTL region by using weighting masks or applying the transformations directly to ROI segmentations. In addition, we evaluated the performance of three fully deformable methods, DARTEL, Diffeomorphic Demons, and LDDMM that are effectively unconstrained by number of degrees of freedom. For each, we first assessed the method's ability to achieve optimal overlap between segmentations of subregions of the MTL across participants. Then we evaluated the smoothness of group average structural images aligned using each method to assess the blur that results when voxels of different tissue types are averaged together. In general, we found that when anatomical segmentation is possible, substantial improvement in registration accuracy can be gained in the MTL even with a small number of deformations. When segmentation is not possible, the fully deformable models provide some improvement over more traditional approaches and in a few cases even approach the performance of the ROI-based approaches. The best performance is achieved when both methods are combined. We note that these conclusions are not limited to the MTL and are easily extendable to other areas of the brain.


Renal dysfunction as a possible cause of essential hypertension in predisposed subjects.
In 65 young normotensive subjects with two hypertensive parents (HP), and in 55 matched subjects with two normotensive parents (NP), the following factors were measured: renal plasma flow (RPF), glomerular filtration rate (GFR) both as Inutest and creatinine clearances; 24-hr urinary output; plasma renin activity (PRA); Na and K in plasma and in 24-hr urine and 24-hr urinary excretion of aldosterone. In 30 HP and in 34 NP, the cardiac output and plasma concentrations of noradrenaline, adrenaline, and dopamine were also measured in the supine position and after 10 min of standing. The HP have greater RPF (P less than 0.01), faster GFR (P less than 0.02), greater 24-hr urinary output (P less than 0.05), and lower PRA (P less than 0.01) than the NP. All the other factors were similar in the two groups of patients. It is proposed that the differences in renal function in the HP and the NP may be due to an abnormality in tubular handling of ions and water in the HP, which may be responsible for the increase in blood pressure in a proportion of patients with essential hypertension.


Neurological complications of celiac disease and autoimmune mechanisms: a prospective study.
Humoral immune mechanisms may have a role in the neurological complications of celiac disease (CD). We assessed 71 CD patients for neurologic manifestations and presence of serum antibodies to neural antigens. Sixteen patients (22.5%) were found to have neurological deficits including headache, depression, entrapment syndromes, peripheral neuropathy, and epilepsy. Antibody reactivity to neural antigens was detected in 30/71 (42.2%) patients. There was no clear correlation between anti-neural reactivity and neurologic dysfunction. Follow-up of 62 patients did not reveal change in electrophysiology or antibodies, regardless of diet. However, in 2 patients with neuropathy, symptoms improved or worsened depending on the diet.


CD4+ T cells help myeloid-mediated killing of immune-evasive tumors.
In a recent study published in Nature, Kruse et al. demonstrated an indirect tumor-killing mechanism orchestrated by a small number of CD4+ effector T cells. These CD4+ T cells can reprogram myeloid cells not just into IFNγ-induced antigen-presenting cells but also into iNOS-expressing tumoricidal effectors that can eradicate immune-evasive tumors.


Low-temperature electrolytic coloration and spectral properties of sucrose crystals.
Sucrose crystals are colored electrolytically at low temperatures and various voltages by using a pointed cathode and a flat anode. Caramels, carbonyl compounds, glycosylamines and free radicals are produced in colored sucrose crystals. No obvious characteristic absorption band in UV and visible wavelength regions is observed in absorption spectrum of uncolored sucrose crystal. Intense characteristic absorption bands of glycosylamines, carbonyl compounds and caramels are observed in absorption spectra of colored sucrose crystals. Production of caramels, carbonyl compounds, glycosylamines and free radicals are explained. Current-time curve for electrolytic coloration of sucrose crystal and its relationship with electrolytic coloration process are given.


Genotoxic effects of fluoride evaluated by sister-chromatid exchange.
The purpose of this investigation was to study the genotoxic potential of fluoride (in the form of sodium fluoride, NaF) using in vitro and in vivo sister-chromatid exchange (SCE) assays with Chinese hamster cells. The NaF concentrations used in cultures of Chinese hamster ovary (CHO) cells ranged from 0 to 6.3 mM, both with and without S9 activation. Fluoride analysis of the culture medium demonstrated that it contained little indigenous fluoride, and the concentration of added fluoride was not affected by the components of the medium or the S9 mix. The CHO cells cultured in 6.3 mM NaF almost vanished, and at the concentration of 5.3 mM NaF in cultures without S9 microsome, only M1 cells were observed. In in vivo studies, Chinese hamsters were intubated with NaF dosages of 0, 0.1, 1.0, 10, 60 and 130 mg/kg, and the bone marrow (CHBM) cells were examined for SCE frequencies. Bone fluoride data showed that the intubated NaF was effectively absorbed. Death occurred in 3 of the 8 animals given 130 mg NaF/kg. The results indicated that NaF, in dosages up to 5.3 mM in CHO cell cultures and 130 mg/kg in in vivo CHBM cells, did not significantly increase the SCE frequencies over those observed in the negative (distilled water) controls. However, examination of the cell cycle revealed an inhibitory effect of NaF on cell proliferation with doses of NaF at or greater than 1.0 mM in cultured CHO cells and at or greater than 60 mg NaF/kg in in vivo CHMB cells. The results of the present study indicated an inhibition of the cell cycle and death of the cells with increasing concentrations of fluoride but not effect of fluoride on SCE frequency in CHO and CHBM cells.


The urban and rural divide for women giving birth in NSW, 1990-1997.
To examine trends in the pregnancy profile and outcomes of urban and rural women. Data were obtained from the NSW Midwives Data Collection on births in NSW, 1990-1997. Associations between place of residence (urban/rural) and maternal factors and pregnancy outcomes were examined, including changes over time. From 1990 to 1997 there were 685,631 confinements in NSW and these mothers resided as follows: 76% metropolitan, 5% large rural centres, 8% small rural centres, 11% other rural areas and 1% remote areas. Rural mothers were more likely to be teenagers, multiparous, without a married or de facto partner, public patients and smokers. Births in rural areas declined, particularly among women aged 20-34 years. Infants born to mothers in remote communities were at increased odds of stillbirth and low Apgar scores (all women) and small-for-gestational- age (SGA) (Indigenous women only). The profile of pregnant women in rural NSW is different from their urban counterparts and is consistent with relative socioeconomic disadvantage and possibly suboptimal maternity services in some areas. While increased risk of SGA is associated with environmental factors such as smoking and nutrition, the reasons the increased risk of stillbirth are unclear. Although there does not appear to be an increase d risk of preterm birth for rural women this may be masked by transfer of high risk pregnancies interstate. Maternity services need to be available and accessible to all rural women with targeting of interventions known to reduce low birthweight and perinatal death.


Crosstalk between the aryl hydrocarbon receptor and hypoxia on the constitutive expression of cytochrome P4501A1 mRNA.
Endothelial cells are a target of halogenated aromatic hydrocarbon toxicity following aryl hydrocarbon receptor (AHR) activation. Further, evidence suggests that AHR has a physiological function in endothelial cells in the absence of exogenous ligands. Understanding these "normal" functions of AHR may help to reveal the mechanisms that contribute to the toxicity of xenobiotic ligands. Thus, this study focused on the crosstalk between hypoxia and AHR in the absence of exogenous ligands. Constitutive CYP1A1 mRNA was measured by real time PCR in human pulmonary microvascular endothelial cells exposed to hypoxia (1 or 2.5% O2), 25 nM AHR siRNA, 25 nM hypoxia-inducible factor (HIF)-2alpha siRNA, or their combinations. Hypoxia significantly induced known hypoxia-regulated genes, and this induction was highly attenuated by HIF-2alpha siRNA, suggesting that HIF-2alpha is a primary mediator of hypoxic responses in these cells. Hypoxia also significantly reduced CYP1A1 mRNA and this reduction was also attenuated by HIF-2alpha siRNA. As expected, AHR siRNA significantly reduced constitutive CYP1A1 mRNA. While the combination of hypoxia plus AHR siRNA reduced CYP1A1 mRNA more than either treatment alone, the reduction was less than additive, suggesting that hypoxia and AHR deficiency may share a common pathway in reducing CYP1A1 expression. Finally, hypoxia significantly reduced AHR mRNA and this reduction was completely prevented by HIF-2alpha siRNA. In conclusion, constitutive CYP1A1 mRNA expression is dependent on AHR and is reduced by hypoxia via a HIF-2alpha-dependent mechanism, which may be mediated by a HIF-2alpha-dependent reduction of AHR expression.


Complete Genome Sequence of a Novel Genotype of Pepper Mild Mottle Virus Infecting Pepper in Chile.
The complete genome sequence of a Pepper mild mottle virus (PMMoV) found on pepper seeds produced in Chile in 2019 was determined using Oxford Nanopore Technologies and Sanger sequencing. The low nucleotide sequence identities (between 89% and 91%) to known PMMoV isolates suggested that this isolate belongs to a novel genotype.


The Equine Temporomandibular Joint: Comparisons Between Standard and Needle Arthroscopic Examination of Cadaver Specimens and Standing Horses.
Definitive diagnosis of equine temporomandibular joint osteoarthritis (TMJ-OA) may require advanced diagnostic imaging. Arthroscopy is a modern, minimally invasive, diagnostic, and treatment modality. Standing arthroscopic treatment of joint disease is a relatively recent advance in equine surgery, despite which there are few published comparisons between the available arthroscopic systems. To compare and contrast two arthroscopic systems for assessing the equine temporomandibular joint compartments in cadavers and standing horses. Experimental study. Phase I involved the assessment of the discotemporal joint (DTJ) and discomandibular (DMJ) joint compartments of both temporomandibular joints (TMJ) of 14 cadaveric equine heads using a caudally placed arthroscopy portal. Joints were initially examined using the needle arthroscope and the results compared to the findings of examination using a 2.5 mm 30° arthroscope system (standard). Three healthy horses were subsequently examined to determine the validity of the procedure in live animals in Phase II. Needle and standard arthroscopy, in combination with mandibular manipulation, allowed evaluation of the caudal aspects of both joint compartments of the TMJ in Phase I. However, the extreme margins of the joint were more commonly visualized using standard arthroscopy. Live horses in phase II were restrained in stocks and both the rostral and caudal aspects of the DTJ and DMJ compartments of both TMJs were examined successfully understanding sedation and local analgesia. The use of a modified Guenther speculum allowed the mandible to be manipulated and offset, which facilitated a complete examination of the joint compartments. Despite adverse behavior encountered during the procedure in one horse, no surgical complications ensued. Not blinded-bias; learning curve. The needle arthroscope system is a relatively inexpensive diagnostic tool, which can be used to evaluate the TMJ in the absence of advanced diagnostic imaging such as computed tomography or magnetic resonance imaging. However, if arthroscopic treatment is required after advanced imaging and pre-operative diagnosis, superior image quality and ease of manipulation may favor the use of the standard equipment.


Low-operating temperature quasi-solid-state potassium-ion battery based on commercial materials.
Quasi-solid-state potassium-ion batteries (QSPIBs) are regarded as one of the most promising safety-enhanced energy storage devices. Herein, a facile method for preparing a potassium-ion composite electrolyte membrane on a large scale is presented for the first time. The as-synthesized membrane displays excellent electrochemical stability, good mechanical flexibility, and high ionic conductivity (9.31 × 10-5 S cm-1 at 25 °C). Furthermore, QSPIBs prepared with this membrane and commercial raw material-based electrodes show superior electrochemical performance even at low temperatures (99.7 mAh g-1 at -20 °C for half QSPIBs and 90.7 mAh g-1 at -15 °C for full QSPIBs), and a promising rate performance (115.6 mAh g-1 for half QSPIBs and 90.9 mAh g-1 for full QSPIBs at 800 mA g-1). The reaction mechanism and structure evolution of a 3,4,9,10-perylene-tetracarboxylicacid-dianhydride (PTCDA) cathode is also systematically studied. The promising characteristics of the prepared low-cost quasi-solid-state potassium-ion batteries in this work open up new possibilities for safer and more durable batteries and a wide range of practical applications in the electronics industry.


Cephalosporin-induced nonconvulsive status epilepticus in a uremic child.
The temporal relationship between convulsive seizures and the administration of beta-lactams has long been recognized. A specific form of seizures, nonconvulsive status epilepticus, is less common and is often manifested by alterations in mental status without associated seizures. It is most commonly encountered in uremic patients and poses a diagnostic challenge because of its nonspecific clinical manifestations. In this report, we describe a child with chronic renal failure who developed nonconvulsive status epilepticus on two separate occasions after administration of a third-generation cephalosporin. Awareness of this potentially treatable condition is crucial to ensure appropriate and prompt medical therapy. To our knowledge, this is the first report of cephalosporin-induced nonconvulsive status epilepticus in a child with chronic renal failure.


Ultraviolet radiation accelerates photodegradation under controlled conditions but slows the decomposition of senescent leaves from forest stands in southern Finland.
Depending on the environment, sunlight can positively or negatively affect litter decomposition, through the ensemble of direct and indirect processes constituting photodegradation. Which of these processes predominate depends on the ecosystem studied and on the spectral composition of sunlight received. To examine the relevance of photodegradation for litter decomposition in forest understoreys, we filtered ultraviolet radiation (UV) and blue light from leaves of Fagus sylvatica and Betula pendula at two different stages of senescence in both a controlled-environment experiment and outdoors in four different forest stands (Picea abies, Fagus sylvatica, Acer platanoides, Betula pendula). Controlling for leaf orientation and initial differences in leaf chlorophyll and flavonol concentrations; we measured mass loss at the end of each experiment and characterised the phenolic profile of the leaf litter following photodegradation. In most forest stands, less mass was lost from decomposing leaves that received solar UV radiation compared with those under UV-attenuating filters, while in the controlled environment UV-A radiation either slightly accelerated or had no significant effect on photodegradation, according to species identity. Only a few individual phenolic compounds were affected by our different filter treatments, but photodegradation did affect the phenolic profile. We can conclude that photodegradation has a small stand- and species-specific effect on the decomposition of surface leaf litter in forest understoreys during the winter following leaf fall in southern Finland. Photodegradation was wavelength-dependent and modulated by the canopy species filtering sunlight and likely creating different combinations of spectral composition, moisture, temperature and snowpack characteristics.


Heterogeneous classes of co-occurring externalizing symptoms in a sample of youth referred for anxiety disorders.
The present study used latent class analysis to identify patterns of externalizing symptoms in a predominantly Hispanic sample of clinic referred anxious youth (N=224; 6-16 years; 54% males) and their parents. Findings revealed that the sample of youth could be classified into three distinct classes: (1) High Externalizing, (2) Moderate Externalizing, and (3) Low Externalizing. The High Externalizing Class was characterized as having a relatively high probability of all ADHD and aggressive symptoms in the clinical range. The Moderate Externalizing Class was characterized as having a relatively high probability of three symptoms in the clinical range: "argues a lot", "disobedient at home", and "fails to finish." The Low Externalizing Class was characterized as having a relatively low probability of all ADHD and aggressive symptoms in the clinical range. The conceptual, empirical, and clinical implications of the findings are discussed.


A chemometric approach for the elucidation of the parameter impact in the hyphenation of field-enhanced sample injection and sweeping in capillary electrophoresis.
The aim of this work was to elucidate the impacts of parameters influencing cation-selective exhaustive injection coupled to sweeping and micellar electrokinetic chromatography (MEKC). A chemometric approach using cationic compounds, acidic conditions (phosphate buffer, pH 2.3) and polyacrylamide-coated capillaries to suppress electroosmotic flow were used. It was demonstrated that the water plug was not useful because of long electrokinetic injections. If conductivity of the high conductivity buffer (HCB) and the HCB to sample conductivity ratio are sufficiently high (>1.66 S/m and >30, respectively), variations of HCB conductivity do not impact sensitivity. The length of the HCB must be long enough so that the most mobile cation remains stacked in this zone for a given injection time. SDS concentration should be as high as possible (the maximum concentration is dictated by MEKC, here 90 mM), so sensitivity is not impacted. We have shown analytes can be lost after electrokinetic injection, when the polarity of the voltage is reversed. Introducing a plug of micellar electrolyte before polarity reversal avoids these losses. Following these recommendations only injection time and sample conductivity impacted sensitivity enhancement. Sample conductivity had to be the lowest as possible and controlled in real case analyses to obtain repeatable enrichment factors.


Cooperative evaluation of human tumor chemosensitivity in the soft-agar assay and its clinical correlations.
In supporting the human-tumor cloning effort of the Southwest Oncology Group, we conducted an independent retrospective study to evaluate the clinical correlations of the soft-agar colony-forming assay developed by Hamburger and Salmon (1977). This study was made with the cooperation of 76 clinicians and 11 hospitals in Greater New Orleans. In a 10-month trial (July 1982 to May 1983), we received 134 human tumors of 26 classifications and achieved 76% success in colony growth from 122 plated samples. Retrospective correlations between the in vitro chemosensitivity of tumor colonies and clinical drug responses were made possible in 31% of the patients. Evaluation of 45 in vitro and in vivo associations indicated a combined sensitivity of 0.65 and a specificity of 0.68 for the assay. Technical refinements and the selectivity of the assay are discussed.


Multi-omics reveal the metabolic patterns in mouse cumulus cells during oocyte maturation.
Bi-directional communication between cumulus cells and the surrounded oocytes is important for the development and functions of both compartments. However, the metabolic framework in cumulus cells has not been systematically described. In the present study, cumulus cells from cumulus-oocyte complexes (COCs) at three key time points were isolated (arrested GV stage, post-hCG 0h; meiotic resumption GVBD stage, post-hCG 3h; and metaphase II stage, post-hCG 12h), and the temporal metabolomic and proteomic profiling were performed. Integrated multi-omics analysis reveals the global metabolic patterns in cumulus cells during mouse oocyte maturation. In particular, we found the active hyaluronic acid metabolism, steroid hormone synthesis, and prostaglandin E2 (PGE2) production in cumulus cells. Meanwhile, accompanying the oocyte maturation, a progressive increase in nucleotide and amino acid metabolism was detected in the surrounding cumulus cells. In sum, the data serve as a valuable resource for probing metabolism during terminal differentiation of ovarian granulosa cells, and provide the potential biomarkers for improving and predicting oocyte quality.


A mutational approach shows similar mechanisms of recognition for the isolated and integrated versions of a protein epitope.
Antibody mAb164 is directed against the native form of the TrpB2 subunit of Escherichia coli tryptophan synthase. It recognizes a synthetic peptide, P11, constituted of residues 273-283 of TrpB, with high affinity. We introduced 16 single and 3 double mutations in each of the two contexts, TrpB2 and P11, and used them as local probes to study the cross-reactivity of mAb164 toward these two antigens. The equilibrium constant, KD, of dissociation from mAb164 was measured for each of the mutant derivatives of TrpB2 and P11 by a competition enzyme-linked immunosorbent assay and compared with the wild type one. The variation of the free energy of interaction, DeltaDeltaG, covered nearly 8 kcal/mol for the different mutations. The values of DeltaDeltaG for the mutant derivatives of TrpB2 and for those of P11 were close and the two sets of values were strongly correlated (r = 0.96). This correlation showed that mAb164 recognized the integrated and isolated versions of residues 273-283 with very similar mechanisms. A few significant differences between the recognitions of TrpB2 and P11 by mAb164 suggested some adaptability of the interaction. The results were compatible with a recognition of residues 273-283 of TrpB in a loop conformation, close to their structure in the crystals of the complete tryptophan synthase, TrpA2TrpB2.


Model chromatin flows: numerical analysis of linear and nonlinear hydrodynamics inside a sphere.
We solve a hydrodynamic model of active chromatin dynamics, within a confined geometry simulating the cell nucleus. Using both analytical and numerical methods, we describe the behavior of the chromatin polymer driven by the activity of motors having polar symmetry, both in the linear response regime as well as in the long-term, fully nonlinear regime of the flows. The introduction of a boundary induces a particular geometry in the flows of chromatin, which we describe using vector spherical harmonics, a tool which greatly simplifies both our analytical and numerical approaches. We find that the long-term behavior of this model in confinement is dominated by steady, transverse flows of chromatin which circulate around the spherical domain. These circulating flows are found to be robust to perturbations, and their characteristic size is set by the size of the domain. This gives us further insight into active chromatin dynamics in the cell nucleus, and provides a foundation for development of further, more complex models of active chromatin dynamics.


Recurrent and residual sebaceous carcinoma after Mohs' excision of the primary lesion.
We reviewed the histories of three patients with sebaceous carcinoma (two of the eyelid and one of the caruncle) who had had their tumors excised by surgeons experienced in the Mohs' technique. In each patient the tumor was considered totally excised. In one patient, residual intraepithelial pagetoid sebaceous carcinoma of the eyelid was detected incidentally when a reparative flap was placed. In the other two patients, invasive sebaceous carcinoma recurred, necessitating orbital exenteration; one patient has regional lymph node metastases. Because of the difficulty in detecting pagetoid spread on frozen sections and the multicentric nature of sebaceous carcinoma, we advocate managing these tumors by wide local excision, checking margins with high-quality permanent sections.


Simultaneous occurrence of mycotoxins in human food commodities from Cameroon.
Eighty-two samples of dried food commodities from Cameroon were screened and quantified for different mycotoxins, including fumonisin B1 (FB1), zearalenone (ZEA), deoxynivalenol (DON), aflatoxin (AF) and ochratoxin A (OTA), by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC), respectively. The percentage of positive samples was as follows: FB1 41%, AF 51%, ZEA 57%, DON 65% and OTA 3%. High FB1 contents were found in maize, averaging 3,684 µg/kg (range: 37-24,225 µg/kg), whereas the highest average ZEA level was found in peanuts (70 µg/kg), followed by maize (69 µg/kg), rice (67 µg/kg) and beans (48 µg/kg) with no ZEA was detected in soybeans. DON contents were low, ranging from 13 to 273 µg/kg, and for AF the average content was 2.6 µg/kg with peanuts and maize as principal substrates. The incidence of OTA was low, with a mean level of 6.4 µg/kg recorded. The majority (79%) of samples contained more than one mycotoxin and the most frequent co-occurrence found was FB1 + ZEA + DON, detected in 21% of samples (mainly maize) analysed. Co-contamination with FB1 + ZEA + DON + AF was found in 11% of the samples. Although a large proportion of samples had fairly low levels of individual mycotoxins, this should be of concern as the co-occurrence of mycotoxins may generate additive or synergistic effect in humans, especially if the respective commodities are consumed almost on a daily basis.


Structure of gas phase radical cation of 1,3,6,8-tetraazatricyclo[188.8.131.52(3,8)] dodecane determined from zero kinetic energy photoelectron spectroscopy.
We report gas-phase vibrational spectroscopy of the ground-state cation of 1,3,6,8-tetraazatricyclo[126.96.36.199(3,8)]dodecane (TTD) using two-color two-photon zero kinetic energy photoelectron spectroscopy. From the distribution of active vibrational modes and comparisons between the experiment and theoretical simulation, we offer proof that the cationic state and the first electronically excited state have the same D(2d) symmetry.


Attenuation Correction for Magnetic Resonance Coils in Combined PET/MR Imaging: A Review.
With the introduction of clinical PET/magnetic resonance (MR) systems, novel attenuation correction methods are needed, as there are no direct MR methods to measure the attenuation of the objects in the field of view (FOV). A unique challenge for PET/MR attenuation correction is that coils for MR data acquisition are located in the FOV of the PET camera and could induce significant quantitative errors. In this review, current methods and techniques to correct for the attenuation of a variety of coils are summarized and evaluated.


Carboxypeptidase E and its splice variants: Key regulators of growth and metastasis in multiple cancer types.
Mechanisms driving tumor growth and metastasis are complex, and involve the recruitment of many genes working in concert with each other. The tumor is characterized by the expression of specific sets of genes depending on its environment. Here we review the role of the carboxypeptidase E (CPE) gene which has been shown to be important in driving growth, survival and metastasis in many cancer types. CPE was first discovered as a prohormone processing enzyme, enriched in endocrine tumors, and later found to be expressed and secreted from many epithelial-derived tumors and cancer cell lines. Numerous studies have shown that besides wild-type CPE, a N-terminal truncated splice variant form of CPE (CPE-ΔN) has been cloned and found to be highly expressed in malignant tumors and cell lines derived from prostate, breast, liver and lung cancers and gliomas. The mechanisms of action of CPE and the splice variant in promoting tumor growth and metastasis in different cancer types are discussed. Mechanistically, secreted CPE activates the Erk/wnt pathways, while CPE-ΔN interacts with HDACs in a protein complex in the nucleus, to recruit various cell cycle genes and metastatic genes, respectively. Clinical studies suggest that CPE and CPE-ΔN mRNA and protein are potential diagnostic and prognostic biomarkers for multiple cancer types, assayed using solid tumors and secreted serum exosomes. CPE has been shown to be a therapeutic target for multiple cancer types. CPE/CPE-ΔN siRNA transported via exosomes and taken up by recipient high metastatic cancer cells, suppressed growth and proliferation of these cells. Thus future studies, delivering CPE/CPE-ΔN siRNA, perhaps via exosomes, to the tumor could be a novel treatment approach to suppress tumor growth and metastasis.


Flower color changes in three Japanese hibiscus species: further quantitative variation of anthocyanin and flavonols.
One anthocyanin and four flavonols were detected from the petals of Hibiscus hamabo, H. tiliaceus and H. glaber. They were identified as cyanidin 3-0- sambubioside, gossypetin 3-O-glucuronide-8-O-glucoside, quercetin 7-O-rutinoside, gossypetin 3-O-glucoside and gossypetin 8-O-glucuronide by UV spectra, LC-MS, acid hydrolysis and HPLC. The flavonoid composition was essentially the same among the petals ofH. hamabo, H. tiliaceus and H. glaber, and there was little quantitative variation, except for cyanidin 3-O-sambubioside, the content of which in the petals ofH. tiliaceus and H. glaber was much higher than in that of H. hamabo. Flower colors of H. tiliaceus and H. glaber change from yellow to red, and that of H. hamabo changes from yellow to orange. These changes were caused by contents of anthocyanin and flavonols, which increased after flowering of H. hamabo, H. tiliaceus and H. glaber.


Nationwide population-based epidemiologic study of childhood and adulthood intussusception in Taiwan.
Most studies have evaluated the epidemiology of intussusception only in children. This was the first nationwide population-based study conducted to investigate the epidemiology and associated medical expenses of intussusception for all age groups in Taiwan. Cases of intussusception were identified from the annual hospitalization discharge claims of the National Health Insurance Research Database with corresponding International Classification of Diseases, Ninth Revision (ICD-9) code 560.0, from January 2000 to December 2007. In total, 7255 incident cases of intussusception were detected. The majority of cases were children younger than 4 years of age. Significant male predominance was observed in the under-10-, 55-59-, and older-than-80-year age groups. The incidence peaked in the 1-2-year age group, reaching as high as 112.84 and 81.96 per 100,000 person-years for males and females, respectively. The incidence of intussusception was very low in adults. However, the medical expenses, number of coexisting neoplasms and malignancies, and hospitalization days were substantially higher in adults than in children. Although coexisting neoplasms developed in 40.8% of adult patients with intussusception, it occurred in only 0.4% of those younger than 3 years. This study is the first to describe detailed age- and sex-specific incidence rates and medical expenses of intussusception for both pediatric and adult groups in Taiwan. There were significant differences between the two groups, with a much higher incidence in young children, but more coexisting neoplasms and malignancies and average medical expenses in adult patients.


Depression and mortality: artifact of measurement and analysis?
Previous research demonstrates various associations between depression, cardiovascular disease (CVD) incidence and mortality, possibly as a result of the different methodologies used to measure depression and analyse relationships. This analysis investigated the association between depression, CVD incidence (CVDI) and mortality from CVD (MCVD), smoking related conditions (MSRC), and all causes (MALL), in a sample data set, where depression was measured using items from a validated questionnaire and using items derived from the factor analysis of a larger questionnaire, and analyses were conducted based on continuous data and grouped data. Data from the PRIME Study (N=9798 men) on depression and 10-year CVD incidence and mortality were analysed using Cox proportional hazards models. Using continuous data, both measures of depression resulted in the emergence of positive associations between depression and mortality (MCVD, MSRC, MALL). Using grouped data, however, associations between a validated measure of depression and MCVD, and between a measure of depression derived from factor analysis and all measures of mortality were lost. Low levels of depression, low numbers of individuals with high depression and low numbers of outcome events may limit these analyses, but levels are usual for the population studied. These data demonstrate a possible association between depression and mortality but detecting this association is dependent on the measurement used and method of analysis. Different findings based on methodology present clear problems for the elucidation and determination of relationships. The differences here argue for the use of validated scales where possible and suggest against over-reduction via factor analysis and grouping.


Invasion speeds with active dispersers in highly variable landscapes: Multiple scales, homogenization, and the migration of trees.
The distribution of many tree species is strongly determined by the behavior and range of vertebrate dispersers, particularly birds. Many models for seed dispersal exist, and are built around the assumption that seeds undergo a random walk while they are being carried by vertebrates, either in the digestive tract or during the process of seed storage (caching). We use a PDF of seed handling (caching and digesting) times to model non-constant seed settling during dispersal, and model the random component of seed movement using ecological diffusion, in which animals make movement choices based purely on local habitat type instead of population gradients. Spatial variability in habitat directly affects the movement of dispersers and leads to anisotropic dispersal kernels. For birds, which can easily move many kilometers, habitat changes on the scale of tens of meters can viewed as rapidly varying. We introduce multiple scales and apply the method of homogenization to determine leading order solutions for the seed digestion kernel (SDK). Using an integrodifference equation (IDE) model for adult trees, we investigate the rate of forest migration. The existing theory for predicting spread rates in IDE does not apply when dispersal kernels are anisotropic. However, the homogenized SDK is isotropic on large scales and depends only on harmonically averaged motilities and modal rates of digestion. We show that speeds calculated using the harmonic average motility accurately predict rates of invasion for the spatially variable system.


Hallermann-Streiff syndrome diagnosed in the seventh decade of life.
Hallermann-Streiff syndrome (HSS) is a rare congenital disorder characterized by dyscephaly, hypotrichosis, microphthalmia, dental anomalies, and cutaneous atrophy. Because of the presence of a characteristic facial appearance, severe visual disturbance, and/or upper airway obstruction, most patients with HSS are diagnosed as having a congenital anomaly as a newborn or early in life. We report a case of HSS that was first recognized when the patient was in her seventh decade of life. A 68-year-old woman presented to our department for decreased vision in both eyes (OU). Her ocular medical history included "ocular injections" in her left eye (OS); laser iridotomies OU, cataract surgery OS, and removal of corneal opacity OU; she did not have a remarkable systemic medical history. At the initial visit to our department, her best-corrected visual acuity was 0.5 in her right eye (OD) and 0.1 OS with +4.0-diopter hyperopic correction OU, corneal opacity due to calcification OU, a shallow anterior chamber and iridotrabecular contact OD were observed. During the surgical intervention OD, the surgeon recognized a "blue sclera," and the physicians initially suspected an underlying systemic malformation. Although mild, she presented with a thin beak-like nose and receding chin. In combination with the ocular features, the proportionate short stature, and a characteristic facial appearance, she was diagnosed with HSS. Patients with HSS who had no clinically significant cosmetic, visual, and respiratory problems early in life may not be recognized as having HSS. The presence of corneal opacity, short axial length, and a blue sclera recognized by ophthalmologists can lead to the correct diagnosis of this congenital disorder.


Morphology and morphogenesis of Apoholosticha sinica n. g., n. sp. (Ciliophora, Hypotrichia), with consideration of its systematic position among urostylids.
This paper investigates the morphology, morphogenesis and SSU rRNA gene-based phylogeny of Apoholosticha sinica n. g., n. sp., isolated from mangrove wetland in Shenzhen, southern China. The new genus Apoholosticha is characterized by its bipartite adoral zone, clearly differentiated frontal cirri arranged in a bicorona, midventral complex composed of midventral pairs only, one marginal cirral row on each side, presence of frontoterminal and transverse cirri, and the lack of a buccal cirrus and caudal cirri. The type species, Apoholosticha sinica n. sp. is diagnosed by the elongated body shape and two kinds of cortical granules. Its main morphogenetic features are similar to that of Pseudokeronopsis except for (1) no buccal cirrus is formed and (2) its macronuclear nodules fuse into a single mass during cell division. Phylogenetic analyses for the new taxon indicate that Apoholosticha n. g. is most closely related to Nothoholosticha and Heterokeronopsis, and falls into the family Pseudokeronopsidae within the core Urostylida clade. In addition, a species that had been misidentified in previous literature is here recognized and assigned to the new genus as Apoholosticha sepetibensis (Wanick and Silva-Neto, 2004) n. comb. (basionym: Pseudokeronopsis sepetibensis Wanick and Silva-Neto, 2004).


Zinc and SARS‑CoV‑2: A molecular modeling study of Zn interactions with RNA‑dependent RNA‑polymerase and 3C‑like proteinase enzymes.
RNA‑dependent RNA‑polymerase (RdRp) and 3C‑like proteinase (3CLpro) are two main enzymes that play a key role in the replication of SARS‑CoV‑2. Zinc (Zn) has strong immunogenic properties and is known to bind to a number of proteins, modulating their activities. Zn also has a history of use in viral infection control. Thus, the present study models potential Zn binding to RdRp and the 3CLpro. Through molecular modeling, the Zn binding sites in the aforementioned two important enzymes of viral replication were found to be conserved between severe acute respiratory syndrome (SARS)‑coronavirus (CoV) and SARS‑CoV‑2. The location of these sites may influence the enzymatic activity of 3CLpro and RdRp in coronavirus disease 2019 (COVID‑19). Since Zn has established immune health benefits, is readily available, non‑expensive and a safe food supplement, with the comparisons presented here between SARS‑CoV and COVID‑19, the present study proposes that Zn could help ameliorate the disease process of COVID‑19 infection.


Infusion efficiency of fluorescein derivatives of different molecular sizes into various starches under atmospheric and high hydrostatic pressures.
Fluorescein isothiocyanate-dextrans (FDs) of different molecular weights were infused into corn, waxy rice, tapioca, and potato starches under atmospheric and high hydrostatic pressures (HHP). FD4, FD10, FD20, and FD40 (Mw 4000, 10,000, 20,000, and 40,000, respectively) were used as infusion materials. Confocal laser scanning microscopy confirmed that all FDs except FD40 infused into corn, waxy rice, and tapioca starches. However, no FDs infused into potato starch. Corn starch had the highest amounts of infused FDs. As molar mass increased, the amount of infused FD decreased in all starches. The infused amounts of FDs in corn starch were similar at 200-300 MPa and atmospheric pressure. Infusion of FDs at 400 MPa was reduced due to partial gelatinization. These results confirm that infusion efficiency is inversely proportional to the molecular weight of the infused material and large materials (Mw > 40,000) cannot be infused into starch granules under atmospheric pressure or HHP. The online version contains supplementary material available at 10.1007/s10068-021-00972-2.


The equilibrium concept and density dependence tests What does it all mean?
Tests of density dependent regulation of population size depend on the concept of equilibrium population size. Such an equilibrium is a purely theoretical construct whose existence in the field is debatable and whose value cannot be measured. An equilibrium is supposed to fluctuate in time, but the extent of the fluctuations relative to those of the population size is unknowable. It is impossible to separate a fluctuating population size from a fluctuating equilibrium value and from fluctuating deviations from an equilibrium value. Because it cannot be determined whether a given population size is above, at, or below equilibrium, the course of population size in unpredictable and density dependence tests cannot be expected to produce useful results. Stabilization tests may provide a more useful alternative.


Nonendocrine theories of the etiology of benign breast disease.
This article summarizes 15 years of clinical and laboratory studies that have continued the search for a biochemical basis for the development and resolution of symptomatic benign fibrocystic disease. The clinical response to diet modifications is presented along with simultaneous laboratory tissue and serum studies. An ongoing study of the clinical response to complete and total methylxanthine abstention, especially caffeine, is presented in the initial part of the article. Following the clinical observations, is a series of laboratory studies, some of which actually preceded the clinical investigation and, in fact, pointed out that a beneficial clinical response might occur in some women following complete abstention. In the last paragraph, we present current information that may identify which women are susceptible to fibrocystic breast disease development.


[Treatment of cancer associated thrombosis: Which role for direct oral anticoagulants in 2018?]
Low molecular weight heparin (LMWH) for at least 3-6 months is the current standard of care for the treatment of cancer associated venous thromboembolism (VTE). Anticoagulation should be continued as long as the cancer is active. In recent years, several direct-acting oral anticoagulants (DOACs) have been approved for the treatment of VTE in the general population. These drugs have progressively emerged as attractive alternatives with the potential to overcome the limitations of LMWH. Due to the lack of high quality prospective data, DOACs are currently not recommended for the treatment of cancer associated VTE yet. Indeed, evidence supporting the use of DOACs in this specific population remains limited, and concerns have been raised about their safety and efficacy in this setting. However, a pattern of increased use of DOACs has been observed in the cancer population. Meta-analyses of Phase III trials of DOACs in VTE as well as analysis of large health care claims databases and non-controlled retrospective studies suggest that DOACs might have similar effectiveness and safety to LMWH for the management of cancer associated VTE. Results from 2 randomized clinical trial (RCT), HOKUSAI-Cancer and SELECT-D, were recently released. Based on a meta-analysis of these 2 RCTs, compared to LMWH, DOACs had lower 6 month recurrent VTE but higher major bleeding. Thus, DOACs should be used with caution in cancer patients and a careful evaluation of the risks and benefits for individual patients is warranted. Ongoing studies will provide much needed evidence to guide clinical care.


Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules.
The overexpression of Aurora kinases in multiple tumors makes these kinases appealing targets for the development of anticancer therapies. This study identified two small molecules with a furanopyrimidine core, IBPR001 and IBPR002, that target Aurora kinases and induce a DFG conformation change at the ATP site of Aurora A. Our results demonstrate the high potency of the IBPR compounds in reducing tumorigenesis in a colorectal cancer xenograft model in athymic nude mice. Human hepatoma up-regulated protein (HURP) is a substrate of Aurora kinase A, which plays a crucial role in the stabilization of kinetochore fibers. This study used the IBPR compounds as well as MLN8237, a proven Aurora A inhibitor, as chemical probes to investigate the molecular role of HURP in mitotic spindle formation. These compounds effectively eliminated HURP phosphorylation, thereby revealing the coexistence and continuous cycling of HURP between unphosphorylated and phosphorylated forms that are associated, respectively, with microtubules emanating from centrosomes and kinetochores. Furthermore, these compounds demonstrate a spatial hierarchical preference for HURP in the attachment of microtubules extending from the mother to the daughter centrosome. The finding of inequality in the centrosomal microtubules revealed by these small molecules provides a versatile tool for the discovery of new cell-division molecules for the development of antitumor drugs.