Laparoscopically harvested omental flap for breast reconstruction in Poland syndrome.
Poland syndrome (PS) is a congenital anomaly of the thoracic wall characterised by a variable degree of unilateral agenesis of pectoralis major and minor muscles associated with ipsilateral breast, rib and upper-arm anomalies. In female patients, breast reconstruction is particularly challenging because of cranial pectoralis muscle defects and partial or complete breast agenesis. Different techniques have been used to treat the thoracic anomaly, including the positioning of an implant, fat transfer or latissimus dorsi transposition, but in some cases these techniques are not feasible resulting in a poor reconstruction. We present our experience in correction of the chest anomaly of PS in a teenage population by using a pedicled laparoscopically harvested omental flap (LOF) to cover a pectoral or breast prosthesis. Procedures were performed by a surgical team which included experienced plastic surgeons and general paediatric surgeons. Preoperative endocrinological and psychological evaluation helped to determine the best timing for the correction. The technique was adopted in 20 patients aged 14-18 years, affected by the syndrome. In all cases, it was possible to harvest an adequate amount of pedicled omentum laparoscopically. Neither significant complications nor conversions to open surgery occurred. The aesthetic outcome of the LOF technique was, in all cases, a soft, natural-looking breast and a satisfactorily corrected infraclavicular defect. The LOF technique is a valid alternative to reconstruction in selected PS cases. It provides a satisfactory reconstruction of the breast and pectoral region and corrects the infraclavicular defect by filling in the area. It avoids the invasiveness and morbidity of a latissimus dorsi transposition.


Inverse effects of dansylation of red blood cell membrane on band 3 protein-mediated transport of sulphate and chloride.
1. Dansylation of the red cell membrane produces inverse effects on SO(4) (2-) and Cl(-) equilibrium exchange. The former is enhanced by several orders of magnitude (Legrum, Fasold & Passow, 1980), the latter is inhibited. Both effects are potentiated after dansylation in the presence of 2-(4-amino-3-sulphophenyl)-6-methyl-7-benzothiazol sulphonic acid (APMB), a disulphonic acid that combines non-covalently with the 4,4'-diisothiocyanate dihydrostilbene-2,2'-disulphonic acid (H(2)DIDS) binding site of the anion transport protein.2. After dansylation the maximum of the pH dependence of SO(4) (2-) exchange near pH 6.3 is replaced by a plateau. When dansylation is performed in the presence of APMB, the plateau is reached at a much higher level at around pH 7.0 and resembles that observed by Funder & Wieth (1976) for Cl(-).3. The mutual interactions between the transfer site, the H(2)DIDS binding site, and the as yet unidentified danysl chloride binding sites were studied in detail. Occupation of the H(2)DIDS binding site by the non-covalently binding agents 4,4'-dinitrostilbene-2,2'-disulphonate (DNDS), 4,4'-bis(acetamido) stilbene-2,2'-disulphonate (DAS) or APMB inhibit the enhanced SO(4) (2-) exchange across the previously dansylated membrane. The apparent K(I) value remains the same as in untreated membranes for DNDS, is reduced to 1/3 for DAS, and to 1/60 for APMB. Conversely, when dansylation is carried out while the H(2)DIDS binding site is occupied by DNDS, APMB or DAS, the enhancement of SO(4) (2-) exchange (as measured after removal of excess dansyl chloride and the additional agent) is prevented by DNDS, augmented by APMB and not affected by DAS. This suggests that the agents stabilize different conformations of the H(2)DIDS binding site that are associated with different accessibilities of the dansyl chloride binding sites.4. The SO(4) (2-) equilibrium exchange as measured at a fixed Cl(-) concentration is enhanced when the Cl(-) concentration at which dansylation is carried out is increased, indicating allosteric interactions between anion binding and the exposure of the dansyl chloride binding sites.5. The enhanced K(+) efflux from dansylated red cells is independent of the described modifications of the dansylation reaction by APMB, DAS or DNDS, demonstrating that there exists no simple correlation between the changes of anion and cation movements that are induced by dansylation.


A stochastic locomotor control model for the nurse shark, Ginglymostoma cirratum.
The locomotor behavior of the nurse shark (Ginglymostoma cirratum) is characterized by 17 variables (frequency and ratios of left, right, and total turns; their radians; straight paths (steps); distance travelled; and velocity) Within each of these variables there is an internal time dependency the structure of which was elaborated together with an improved statistical model predicting their behavior within 90% confidence limits. The model allows for the sensitive detection of subtle locomotor response to sensory stimulation as values of variables may exceed the established confidence limits within minutes after onset of the stimulus. The locomotor activity is well described by an autoregression time series model and can be predicted by only seven variables. Six of these form two independently operating clusters. The first one consists of: the number of right turns, the distance travelled and the mean velocity; the second one of: the mean size of right turns, of left turns, and of all turns. The same clustering is obtained independently by a cluster analysis of cross-sections of the seven time series. It is apparent that, among a total of 17 locomotor variables, seven behave as individually independent agents, presumably controlled by seven separate and independent centers. The output of each center can only be predicted by its own behavior. In spite of the individual of the seven variables, their internal structure is similar in important aspects which may result from control by a common command center. The shark locomotor model differs in important aspects from the previously constructed for the goldfish. The interdependence of the locomotor variables in both species may be related to the control mechanisms postulated by von Holst for the coordination of rhythmic fin movements in fishes. A locomotor control model for the nurse shark is proposed.


Case report: Dropped gallstones diagnosis is hindered by incomplete surgical notes and a low index of suspicion.
Diagnosis and treatment of dropped gallstones (DG) complications can be delayed due to a low index of suspicion by treating physicians. This delay may derive from incomplete surgical notes that disregard and underreport DG. This report highlights the management of two cases of DG-related abscesses with incomplete surgical notes and how a high index of suspicion can bear positively on treatment results. Two patients, a 62 and a 71-year-old female, presented intraabdominal abscess' resulting from DG from a prior laparoscopic cholecystectomy (LC). In neither patient did the surgical notes report the occurrence of DG. Both patients were treated with percutaneous drainage; however, their recovery was markedly different. In one case, an association with DG was not suggested until after several months of repeated abscess occurrence. In the other case, it was suggested early in the treatment, allowing for a shorter and improved recovery. DG diagnosis is hindered by incomplete surgical notes and a low index of suspicion. Improvements in management can occur only if surgeons dependably report DG episodes. Percutaneous drainage of DG abscess under local anesthesia is less invasive than a laparoscopic or surgical approach and can be performed on an outpatient basis with or without using various stone fragmentation tools. A high index of suspicion of DG can positively impact the treatment of these cases, therefore, reporting DG events during surgery is necessary. Percutaneous drainage with saline irrigation is safe and effective in selected patients with DG abscesses.


Some biochemical and physiochemical properties of the potent uncoupler SF 6847 (3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile).
Various physicochemical and biochemical properties of the most potent uncoupler of oxidative phosphorylation known to date 3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile (SF 6847), such as pH dependence of the uncoupling activity and binding to mitochondria, spectral properties in the presence of different types of liposomes, biopolymers and mitochondria, and effects on model membrane systems have been investigated. From the results, it is concluded that the uncoupler most likely is localized in the phospholipid part of the membrane.


The toluidine blue-membrane filter method: absorption spectra of toluidine blue stained bacterial cells and the relationship between absorbance and dry mass of bacteria.
Propan-2-ol did not leach dye from toluidine blue stained bacteria on membrane filters but ethanol did. The absorption spectra of toluidine blue stained cells of two Gram-positive and two Gram-negative organisms differed with the latter organisms exhibiting metachromasia. The results suggest that toluidine blue stains the cell envelope. Linear regression equations were derived for each of four organisms, Streptococcus cremoris, Lactobacillus bulgaricus, Pseudomonas fluorescens and Escherichia coli, relating absorbance at the peak of the absorption spectra and the mass of cells on the filters. With these equations it should be possible to determine mass of cells with an error between 3% and 7.5% depending on the organism. Since the regression equations are similar, the amount of toluidine blue retained per milligram of cells may be constant under standard conditions, irrespective of species.


Review article: diagnostic and therapeutic approach to persistent abdominal pain beyond irritable bowel syndrome.
Persistent abdominal pain (PAP) poses substantial challenges to patients, physicians and healthcare systems. The possible aetiologies of PAP vary widely across organ systems, which leads to extensive and repetitive diagnostic testing that often fails to provide satisfactory answers. As a result, widely recognised functional disorders of the gut-brain interaction, such as irritable bowel syndrome and functional dyspepsia, are often diagnosed in patients with PAP. However, there are a number of less well-known differential diagnoses that deserve consideration. To provide a comprehensive update on causes of PAP that are relatively rare in occurrence. A literature review on the diagnosis and management of some less well-known causes of PAP. Specific algorithms for the diagnostic work-up of PAP do not exist. Instead, appropriate investigations tailored to patient medical history and physical examination findings should be made on a case-by-case basis. After a definitive diagnosis has been reached, some causes of PAP can be effectively treated using established approaches. Other causes are more complex and may benefit from a multidisciplinary approach involving gastroenterologists, pain specialists, psychologists and physiotherapists. This list is inclusive but not exhaustive of all the rare or less well-known diseases potentially associated with PAP. Persistent abdominal pain (PAP) is a challenging condition to diagnose and treat. Many patients undergo repeated diagnostic testing and treatment, including surgery, without achieving symptom relief. Increasing physician awareness of the various causes of PAP, especially of rare diseases that are less well known, may improve patient outcomes.


Stimulation of 1,25-dihydroxycholecalciferol production by prolactin and related peptides in intact renal cell preparations in vitro.
Ovine prolactin stimulated the 1 alpha-hydroxylase activity in isolated renal tubules and especially in primary kidney cell cultures, both prepared from vitamin D-deficient chicks. In primary chick kidney cell cultures, treated for 48 h with 1,25-dihydroxycholecalciferol (to induce the 24-hydroxylase activity) ovine prolactin, after a 1 h incubation period, stimulated the 1 alpha-hydroxylase activity without affecting the 24-hydroxylase activity. Similar results were obtained with related peptide hormones such as human growth hormone, chicken growth hormone, and human placental lactogen. These observations are discussed in relation to the possible role of these peptide hormones as modulators of 1,25-dihydroxycholecalciferol production in physiological situations of calcium stress, such as pregnancy, lactation, growth in mammals and egg laying in birds.


Immunological activity of a proline-rich polypeptide from ovine colostrum.
The results presented in the paper showed that PRP increased permeability of skin vessels in guinea pigs and that PRP stimulates or suppresses the immunological response in mice, depending on the magnitude of the response.


Development and validation of a prognostic index for 2-year mortality in Chinese older residents living in nursing homes.
There is no mortality prediction index for Chinese nursing home older residents. The objective of this study was to derive and validate a 2-year mortality prognostic index for them. We carried out a prospective cohort study on 1120 older residents from 12 nursing homes of Hong Kong. We obtained potential predictors of mortality and carried out updated functional assessment. Each risk factor associated independently with 2-year mortality in a derivation cohort was assigned a score based on the odds ratio, and risk scores were calculated for each participant by adding the points of risk factors present. Similar analysis was carried out on the validation cohort. Independent predictors of mortality included: aged 86-90 years (3 points); aged ≥ 91 years (4 points); Charlson comorbidity index ≥ 4 (6 points); Barthel Index 5-60 (5 points); Barthel Index 0 (10 points); number of hospitalizations in the preceding year (Adbefore) 1 (4 points); Adbefore 2 (5 points) and Adbefore ≥ 3 (6 points). In the derivation cohort, 2-year mortality was 10.8% in the low-risk group (≤ 4 points) and 59.9% in the high-risk group (≥ 14 points). In the validation cohort, 2-year mortality was 11.8% in the low-risk group and 60.4% in the high-risk group. The receiver-operator characteristic curve area was 0.761 for the derivation cohort and 0.742 for the validation cohort. Our prognostic index had satisfactory discrimination and calibration in an independent sample of Chinese nursing home older residents. It can be used to identify older residents with a high risk for poor outcomes, who need a different level of care.


Amperometric sensor for hydrogen peroxide based on direct electron transfer of spinach ferredoxin on Au electrode.
A protein-based electrochemical sensor for hydrogen peroxide (H(2)O(2)) was developed by an easy and effective film fabrication method where spinach ferredoxin (Fdx) containing [2Fe-2S] metal center was cross linked with 11-mercaptoundecanoic acid (MUA) on a gold (Au) surface. The surface morphology of Fdx molecules on Au electrodes was investigated by atomic force microscopy (AFM). Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were employed to study the electrochemical behavior of adsorbed Fdx on Au. The interfacial properties of the modified electrode were evaluated in the presence of Fe(CN)(6)(3-/4-) redox couple as a probe. From CV, a pair of well-defined and quasi-reversible redox peaks of Fdx was obtained in 10mM, pH 7.0 Tris-HCl buffer solution at -170 and -120mV respectively. One electron reduction of the [2Fe-2S](2+) cluster occurs at one of the iron atoms to give the reduced [2Fe-2S](+). The formal reduction potential of Fdx ca. -150mV (vs. Ag/AgCl electrode) at pH 7.0. The electron-transfer rate constant, k(s), for electron transfer between the Au electrode and Fdx was estimated to be 0.12s(-1). From the electrochemical experiments, it is observed that Fdx/MUA/Au promoted direct electron transfer between Fdx and electrode and it catalyzes the reduction of H(2)O(2). The Fdx/MUA/Au electrode displays a linear increase in amperometric current for increasing concentration of H(2)O(2).The sensor calibration plot was linear with r(2)=0.998 with sensitivity approximately 68.24μAm M(-1)cm(-2). Further, the effect of nitrite on the developed sensor was examined which does not interfere with the detection of H(2)O(2). Finally, the addition of H(2)O(2) on MUA/Au electrode was observed which has no effect on amperometric current.


Adjuvant chemotherapy in advanced head and neck cancer. An update.
Two courses of triple-agent chemotherapy were given to 47 patients with advanced head and neck cancer. All but one patient with a nasopharyngeal carcinoma had resectable stage III and IV squamous cell carcinoma. Eighty-eight percent of the patients responded to the chemotherapy with a 50 percent or greater decrease in tumor size. Forty-three patients underwent surgical resection and 19 were histologically upgraded to stage II or better (T less than 2 cm, N0). None of these 19 patients have relapsed, with follow-up ranging from 12 to 42 months. In 12 of the 47 patients, recurrent tumor developed within the first 18 months of follow-up.


Effect of maternal smoking during pregnancy on passive respiratory mechanics in early infancy.
We studied the effect of prenatal maternal cigarette smoking on passive expiratory mechanics in 53 healthy infants tested early in infancy (mean +/- SD, 5.1 +/- 1.5 weeks). Maternal smoking was measured by: 1) questionnaire reports of the number of cigarettes smoked per day; and 2) urine cotinine concentrations (corrected for creatinine) at each visit. Respiratory system mechanics were assessed by the single-breath occlusion-passive-flow-volume maneuver. In ten infants born to smoking mothers the time constant of the respiratory system was 23% reduced [0.34 vs. 0.44 s; 95% confidence interval (CI), -45% + 1%; P = 0.06]. This was related to an estimated 13% decrease in respiratory system compliance (4.86 vs. 5.62 mL/cmH2O; 95%CI, -33% + 6%; P = 0.18) and a 10% reduction in respiratory system resistance (0.073 vs. 0.081 cm H2O/mL/s; 95%CI, -42% + 22%; P = 0.56). Functional residual capacity (FRC), measured by helium-dilution, was also decreased by 13% (78 vs. 90 mL; 95%CI, -27% + 0.3%; P = 0.06) in smoke-exposed infants. Forced expiratory flow rates at FRC obtained by thoraco-abdominal compression were reduced by 28% in infants of smoking mothers (VFRC, 99 vs. 138 mL/s; 95%CI, -54% + 2%; P = 0.04) as reported previously in a larger sample from this population. This study was limited by small numbers of infants exposed to smoking during pregnancy and by ethnic imbalance among the smoking-exposed and unexposed groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Computer-aided diagnosis in rheumatic diseases using ultrasound: an overview.
Clinical evaluation of rheumatic and musculoskeletal diseases through images is a challenge for the beginner rheumatologist since image diagnosis is an expert task with a long learning curve. The aim of this work was to present a narrative review on the main ultrasound computer-aided diagnosis systems that may help clinicians thanks to the progress made in the application of artificial intelligence techniques. We performed a literature review searching for original articles in seven repositories, from 1970 to 2019, and identified 11 main methods currently used in ultrasound computer-aided diagnosis systems. Also, we found that rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and idiopathic inflammatory myopathies are the four musculoskeletal and rheumatic diseases most studied that use these innovative systems, with an overall accuracy of > 75%.


Identification of phosphorylation site on PARP1 mediating its cytosolic translocation in virus-infected HeLa cells.
Poly (ADP-ribose) polymerase 1 (PARP1) localization is controlled by its phosphorylation state. Here, we describe a protocol to monitor PARP1 subcellular localization in HSV-1-infected HeLa cells using immunofluorescence microscopy and cytoplasmic/nuclear fractionation. We detail steps to identify phosphorylation sites on PARP1 using conserved motif analysis and mass spectrometry. This protocol can be applied to the study of other protein phosphorylation events in other cell types. For complete details on the use and execution of this protocol, please refer to Wang et al. (2022).


Winter temperatures limit population growth rate of a migratory songbird.
Understanding the factors that limit and regulate wildlife populations requires insight into demographic and environmental processes acting throughout the annual cycle. Here, we combine multi-year tracking data of individual birds with a 26-year demographic study of a migratory songbird to evaluate the relative effects of density and weather at the breeding and wintering grounds on population growth rate. Our results reveal clear support for opposing forces of winter temperature and breeding density driving population dynamics. Above-average temperatures at the wintering grounds lead to higher population growth, primarily through their strong positive effects on survival. However, population growth is regulated over the long term by strong negative effects of breeding density on both fecundity and adult male survival. Such knowledge of how year-round factors influence population growth, and the demographic mechanisms through which they act, will vastly improve our ability to predict species responses to environmental change and develop effective conservation strategies for migratory animals.


Preclinical Drug Response Metric Based on Cellular Response Phenotype Provides Better Pharmacogenomic Variables with Phenotype Relevance.
High-throughput screening of drug response in cultured cell lines is essential for studying therapeutic mechanisms and identifying molecular variants associated with sensitivity to drugs. Assessment of drug response is typically performed by constructing a dose-response curve of viability and summarizing it to a representative, such as IC50. However, this is limited by its dependency on the assay duration and lack of reflections regarding actual cellular response phenotypes. To address these limitations, we consider how each response-phenotype contributes to the overall growth behavior and propose an alternative method of drug response screening that takes into account the cellular response phenotype. In conventional drug response screening methods, the ranking of sensitivity depends on either the metric used to construct the dose-response curve or the representative factor used to summarize the curve. This ambiguity in conventional assessment methods is due to the fact that assessment methods are not consistent with the underlying principles of population dynamics. Instead, the suggested phenotype metrics provide all phenotypic rates of change that shape overall growth behavior at a given dose and better response classification, including the phenotypic mechanism of overall growth inhibition. This alternative high-throughput drug-response screening would improve preclinical pharmacogenomic analysis and the understanding of a therapeutic mechanism of action.


[Ability of the opiate kappa-agonist bremazocine to facilitate the flexor reflex of the right hindlimb in spinal rats].
It has been found that bremazocine predominantly enhances the flexor reflex of the right hind limb, without affecting the left limb. The similarity of the visual data measuring the asymmetry of the pose and the asymmetry of EMG responses to painful stimulation has a high probability. No correlation between the asymmetry of the pose and EMG extensor activity has been found.


Development of model infectious disease protocols for fire and EMS personnel.
To develop model infectious disease exposure plans for emergency medical services agencies in King County, Washington. All fire departments in King County, Washington, were surveyed to determine their pathogen exposure policies. After these agencies were surveyed, model response plans were developed for both bloodborne and airborne pathogen exposure. Twenty-four of the 35 fire departments in King County submitted infectious disease exposure policies. There was diversity among the plans, and not all were deemed able to provide prophylaxis in a timely fashion. Based on this lack of uniformity among response plans, model response plans were developed for bloodborne and airborne infectious disease pathogens. Great variety was present throughout the exposure plans currently in use throughout King County, Washington. Model plans would likely universalize response to pathogen exposure and help to ensure prompt and appropriate postexposure prophylaxis.


Effect of glutathione modulation using buthionine sulfoximine on DNA methylation by dimethylnitrosamine in the rat.
An in vivo study was carried out in order to determine whether glutathione (GSH) might serve as a scavenger for the supposed electrophilic methylating fragment derived from dimethylnitrosamine (DMN) and thus function to decrease the degree of cellular macromolecule interaction, estimated by measuring the DNA methylation yield. After a 4-hr pretreatment with DL-buthionine-SR-sulfoximine (BSO), a specific inhibitor of GSH synthesis, male Sprague-Dawley rats were dosed with radiolabeled DMN (250 micrograms/kg). Four hours later the animals were killed and the livers and kidneys were excised. The DNA isolated from these organs was hydrolyzed in mild acid, and the liberated purines were quantified utilizing HPLC and liquid scintillation counting. The 70-75% GSH depletion in the liver and kidney resulting from BSO pretreatment did not have any significant effect on the degree of DNA methylation as assessed by the 7-methylguanine/guanine yield. In control experiments we found that DMN doses greater than 1 mg/kg had a marked effect on liver and kidney GSH levels after 4 hr.


Complementary expression of melanosomal antigens and constant expression of pigment-independent antigen during the evolution of melanocytic tumours.
We have generated monoclonal antibodies (MoAbs) against melanosomal proteins (MoAb 1C11 and MoAb HMSA-1) and a cytoplasmic protein strongly synthesized in neoplastic melanocytes but not associated with melanogenesis (MoAb 7H11). An immunohistochemical study of paraffin sections showed that nearly 90% of epidermal neoplastic melanocytes, including melanomas, expressed 1C11 antigen, whereas this antigen was poorly preserved in dermal melanocytic cells except melanomas. HMSA-1 antigen was expressed in a complementary manner to 1C11 antigen, being found in dermal naevus cells but not generally in the epidermal regions, except for dysplastic naevi and melanomas. In contrast, 7H11 antigen was distributed in nearly 90% of melanocytic tumours except solar lentigo and lentigo maligna lesions. The failure of MoAb 1C11 to react with dermal melanocytes may reflect a subtle alteration in melanogenesis during tumour evolution. Overall, the combined use of MoAbs serves as an accurate diagnosis of melanocytic tumours, the pigment-independent MoAb 7H11 being particularly useful for amelanotic and metastatic lesions.


Correlation of Short Knee Radiographs and Full-length Radiographs in Patients Undergoing Total Knee Arthroplasty.
The clinical success and longevity of a primary total knee arthroplasty (TKA) in large part depend on our ability to control coronal alignment. However, controversy exists regarding which radiographs to use for the most accurate interpretation. The study assesses the accuracy of coronal alignment measurements using a single short knee radiograph (SKR) in comparison with full-length radiographs (FLRs). Using our institutional database, we retrieved radiographs of all patients who have had pre- and postoperative FLRs for their primary TKA in 2014. The following measurements were obtained on both short and long radiographs: femoral-tibial angle (FTA), anatomic lateral distal femoral angle, medial proximal tibial angle, condylar-plateau angle, and condylar-plateau distance. A reliability analysis was conducted between the pre- and postoperative SKRs and FLRs using the intraclass correlation coefficient (ICC). Radiographs of 236 limbs were included in the analysis. The FTA showed an ICC of 0.84 and 0.69 on the pre- and postoperative radiographs, respectively. Good ICC was seen in the lateral distal femoral angle in both the pre- and postoperative radiographs; these were 0.70 and 0.67, respectively. Also, the medial proximal tibial angle showed good to excellent correlation, with an ICC of 0.83 on the preoperative and 0.66 on the postoperative radiographs. This study illustrates that SKRs could be an appropriate substitute for FLRs for the evaluation of primary TKA coronal alignment, especially in the postoperative assessment of these patients. Level III.


Cells immersed in collagen matrices show a decrease in plasma membrane fluidity as the matrix stiffness increases.
Cells are constantly adapting to maintain their identity in response to the surrounding media's temporal and spatial heterogeneity. The plasma membrane, which participates in the transduction of external signals, plays a crucial role in this adaptation. Studies suggest that nano and micrometer areas with different fluidities at the plasma membrane change their distribution in response to external mechanical signals. However, investigations linking fluidity domains with mechanical stimuli, specifically matrix stiffness, are still in progress. This report tests the hypothesis that the stiffness of the extracellular matrix can modify the equilibrium of areas with different order in the plasma membrane, resulting in changes in overall membrane fluidity distribution. We studied the effect of matrix stiffness on the distribution of membrane lipid domains in NIH-3 T3 cells immersed in matrices of varying concentrations of collagen type I, for 24 or 72 h. The stiffness and viscoelastic properties of the collagen matrices were characterized by rheometry, fiber sizes were measured by Scanning Electron Microscopy (SEM) and the volume occupied by the fibers by second harmonic generation imaging (SHG). Membrane fluidity was measured using the fluorescent dye LAURDAN and spectral phasor analysis. The results demonstrate that an increase in collagen stiffness alters the distribution of membrane fluidity, leading to an increasing amount of the LAURDAN fraction with a high degree of packing. These findings suggest that changes in the equilibrium of fluidity domains could represent a versatile and refined component of the signal transduction mechanism for cells to respond to the highly heterogeneous matrix structural composition. Overall, this study sheds light on the importance of the plasma membrane's role in adapting to the extracellular matrix's mechanical cues.


Vasopressor dose equivalence: A scoping review and suggested formula.
Calculating equipotent doses between vasopressor agents is necessary in clinical practice and research pertaining to the management of shock. This scoping review summarizes conversion ratios between vasopressors and provides a formula to incorporate into study designs. Medline, Embase and Web of Science databases were searched from inception to 21st October 2020. Additional papers were obtained through bibliography searches of retrieved articles. Two investigators assessed articles for eligibility. Clinical trials comparing the potency of at least two intravenous vasopressors (norepinephrine, epinephrine, dopamine, phenylephrine, vasopressin, metaraminol or angiotensin II), with regard to an outcome of blood pressure, were selected. Of 16,315 articles, 21 were included for synthesis. The range of conversion ratios equivalent to one unit of norepinephrine were: epinephrine (0.7-1.4), dopamine (75.2-144.4), metaraminol (8.3), phenylephrine (1.1-16.3), vasopressin (0.3-0.4) and angiotensin II (0.07-0.13). The following formula may be considered for the calculation of norepinephrine equivalents (NE) (all in mcg/kg/min, except vasopressin in units/min): NE = norepinephrine + epinephrine + phenylephrine/10 + dopamine/100 + metaraminol/8 + vasopressin*2.5 + angiotensin II*10. A summary of equipotent ratios for common vasopressors used in clinical practice has been provided. Our formula may be considered to calculate NE for studies in the intensive care unit.


Effect of restricted protein diet supplemented with keto analogues in end-stage renal disease: a systematic review and meta-analysis.
To evaluate the efficacy and safety of the restricted protein diet supplemented with keto analogues when applied in end-stage renal disease (ESRD). The Cochrane Library, PubMed, Embase, CBM and CENTRAL databases were searched and reviewed up to January 2017. Clinical trials were analyzed using RevMan 5.3 software. Five randomized controlled trials were selected and included in this study according to our inclusion and exclusion criteria. Changes in serum albumin, PTH, triglyceride, cholesterol, calcium, phosphorus, hemoglobin, Kt/v and CRP before and after treatment were analyzed. Meta-analysis results indicated that, compared with normal protein diet, low-protein diet (LPD) supplemented with keto analogues (sLPD) could improve serum albumin (P < 0.00001), hyperparathyroidism (P < 0.00001) and hyperphosphatemia (P = 0.008). No differences in triglyceride, cholesterol, hemoglobin, Kt/v and CRP were observed between different protein intake groups. Restricted protein diet supplemented with keto analogues (sLPD) may improve nutritional status and prevent hyperparathyroidism in ESRD patients. The current data were mainly obtained from short-term, single-center trails with small sample sizes and limited nutritional status indexes, indicating a need for further study.


The impact of prelaryngeal node metastases on early glottic cancer treatment results.
The aim of the study was to examine the impact of positive prelaryngeal node on the outcome of early glottic cancer and to compare the rate of local and regional recurrences and overall survival rates in patients with positive and negative Delphian node (DN). In the years 1989-2008, a consecutive cohort of 212 patients with T1b and T2 glottic cancer with anterior commisure involvement were treated by means of supracricoid partial reconstructive laryngectomies. No adjuvant radiotherapy was administered. Out of 212 patients, in 75 suspected prelaryngeal tissue was found, harvested and separately sent for histological investigation (16-thyroid, 11-fat, 14-connective tissue, 34-lymph nodes). In 137 remaining cases, there were only muscles and fascia without even a small amount of tissue to be taken. In 16 cases out of the whole group, metastases were found. 33 patients with positive ultrasound findings on the lateral neck underwent selective neck dissection; in 4 cases metastases were confirmed. Local and regional recurrence developed in 37 out of 212 patients (17.5%). There was significant correlation between local relapse and prelaryngeal node metastases; out of 20 cases with local recurrence, 13 had positive DN (P < 0.005). There was also significant correlation between nodal relapses and DN metastases; out of 22 cases with nodal relapse, 12 had positive DN and 10 were DN negative (P < 0.005). The organ preservation rates for DN positive and DN negative patients were 62.5 and 93.88%, respectively. There was noted a significant difference in the mean survival between the groups with positive and negative DN (P = 0.004; 38.7 vs. 49.3 months, respectively). In conclusion, positive DN seems to be a strong isolated factor influencing prognosis in patients with early glottic cancer. DN metastases are responsible for the increased rates of local and nodal relapses, decreased chances of organ preservation and poor overall survival rates.


Streptomyces araujoniae sp. nov.: an actinomycete isolated from a potato tubercle.
The taxonomic position of a streptomycete isolated from a potato tubercle was determined by using a polyphasic approach. The organism had chemotaxonomic and morphological properties consistent with its classification in the genus Streptomyces and formed a distinct phyletic line in the Streptomyces 16S rRNA gene tree. It was found to be closely related to Streptomyces celluloflavus NRRL B-2493(T) (99.4 % 16S rRNA gene similarity) and shared a 99.0 % 16S rRNA gene similarity value with Streptomyces albolongus NRRL B-3604(T) and Streptomyces cavourensis subsp. cavourensis NBRC 13026(T); low levels of DNA-DNA relatedness with these organisms showed that the isolate belonged to a distinct genomic species. The isolate was distinguished readily from the type strains of these species using a combination of morphological and other phenotypic properties. On the basis of these results, it is proposed that isolate ASBV-1(T) (= CBMAI 1465(T) = CCMA 894(T) = NRRL B-24922(T)) be classified as the type strain of Streptomyces araujoniae sp. nov.


Partial seizures of frontal and temporal origin.
The majority of medically refractory partial epilepsies arise in the frontal and temporal lobes and represent a major challenge to the neurologist. The phenomenology of seizures from these regions is diverse and fascinating, at times lying on the border of many medical specialties. An appreciation of the wealth of potential phenomena can lead to more accurate diagnosis and treatment.


Megarrectosigmoides por constipación crónica idiopática, sigmoidectomía con robot en el paciente pediátrico. Primer caso en México.
We present the first pediatric case of Da Vinci Xi robot-assisted video sigmoidectomy in a 9-year-old male with chronic idiopathic constipation refractory to medical treatment and megarectosigmoid. He underwent sigmoidectomy with primary anastomosis without exceeding the peritoneal reflection. Sigmoidectomy in patients with intractable chronic constipation results in dramatic improvement, with reduction or elimination of laxative measures. Robot-assisted sigmoid resection is a safe minimally invasive alternative in the pediatric patient.


Sleep deprivation before stroke is neuroprotective: a pre-ischemic conditioning related to sleep rebound.
We have previously shown in a rat model of focal cerebral ischemia that sleep deprivation after stroke onset aggravates brain damage. Others reported that sleep deprivation prior to stroke is neuroprotective. The main aim of this study was to test the hypothesis that the neuroprotection may be related to an increase in sleep (sleep rebound) during the acute phase of stroke. Male Sprague Dawley rats (n=36) were subjected to continuous polygraphic recordings for baseline, total sleep deprivation (TSD), and 24h after ischemia. TSD for 6h was performed by gentle handling and immediately followed by ischemia. Focal cerebral ischemia was induced by permanent occlusion of distal branches of the middle cerebral artery. Control experiments included ischemia without SD (nSD) and sham surgery with TSD (n=6/group). Shortly after stroke, the amount of slow wave sleep (SWS) and paradoxical sleep (PS) increased significantly (p<0.05) in the TSD/ischemia, resulting in an increase in the total sleep time by 30% compared to baseline, or by 20% compared with the nSD/ischemia group. The infarct volume decreased significantly by 50% in the TSD/ischemia compared to nSD group (p<0.02). Removal of sleep rebound by allowing TSD-rats sleep for 24h before ischemia eliminated the reduction in the infarct size. Sleep deprivation results in sleep rebound and reduces brain damage. Sleep rebound may be causally related to the neuroprotection.


Receptor binding in various tissues of PGE2, PGF2 alpha and sulprostone, a novel PGE2-derivative.
Sulprostone is a tissue-specific PGE2-derivative with high abortifacient activity in various species including man. The dissociation constant KD of the receptor binding of this compound was compared with PGE2 and PGF2 alpha in various tissue preparations of different species. A structure-binding relationship was developed from competition curves after a logit/log transformation. It is demonstrated that the relative affinities of Sulprostone, PGE2 and PGF2 alpha remain essentially constant in all the tissues investigated. It is concluded that the tissue-specificity of Sulprostone cannot be ascribed to structural differences of the receptor molecule.


Recovery of the ability to induce immune resistance against L1210 lymphatic leukemia in semisyngeneic CD2F1 mice after lethal irradiation and reconstitution with bone marrow purged of leukemia with mafosfamide (ASTA Z 7654).
Balb/c x DBA/2 F1 (CD2F1) mice were lethally irradiated (TBI) and reconstituted with syngeneic bone marrow cells (SBMT) untreated or treated with mafosfamide (ASTA Z 7654) for ex vivo purging of semisyngeneic L1210 leukemia (TBI + SBMT or TBI + SBMT-Maf mice, respectively). At various times after irradiation and reconstitution mice were injected intraperitoneally four times at weekly intervals with 10(6) immunogenic L1210-Maf cells (L1210 cells treated in vitro with mafosfamide for inhibition of their growth in vivo). As positive controls we immunized normal (non-irradiated) CD2F1 mice. Full resistance against L1210 leukemia (as compared to normal immunized mice) could be obtained in TBI + SBMT and TBI + SBMT-Maf mice when the immunization procedure was started from day +28 or day +56 after transplantation, respectively. Earlier immunization of TBI + SBMT mice (from day +14) or TBI + SBMT-Maf mice (from day +14 or +28) caused only partial resistance against the leukemia.


Ofatumumab maintenance versus observation in relapsed chronic lymphocytic leukaemia (PROLONG): an open-label, multicentre, randomised phase 3 study.
Ofatumumab is a human anti-CD20 monoclonal antibody that has proven efficacy as monotherapy in refractory chronic lymphocytic leukaemia. We assessed the efficacy and safety of ofatumumab maintenance treatment versus observation for patients in remission after re-induction treatment for relapsed chronic lymphocytic leukaemia. This open-label, multicentre, randomised phase 3 study enrolled patients aged 18 years or older from 130 centres in 24 countries who had chronic lymphocytic leukaemia in complete or partial remission after second-line or third-line treatment. Eligible patients had a WHO performance status of 0-2, had a response assessment within the previous 3 months, did not have refractory disease, autoimmune haemolytic anaemia requiring treatment, chronic or active infection requiring treatment, and had not previously received maintenance treatment or autologous or allogeneic stem-cell transplant. Using a randomisation list generated by a central computerised system and an interactive voice recognition system, we randomly assigned (1:1) patients to receive ofatumumab (300 mg followed by 1000 mg 1 week later and every 8 weeks for up to 2 years) or undergo observation. Randomisation was stratified by number and type of previous treatment and remission status after induction treatment (block size of four). Treatment assignment was open label. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. We report the results of a prespecified interim analysis after two-thirds of the planned study events (disease progression or death) had happened. This trial is closed to accrual but follow-up is ongoing. This trial is registered with ClinicalTrials.gov, number NCT00802737. Between May 6, 2010, and June 19, 2014, we enrolled 474 patients: 238 patients were randomly assigned to receive ofatumumab maintenance treatment and 236 to undergo observation. One (<1%) patient in the ofatumumab group did not receive the allocated intervention (withdrawal of consent). The median follow-up was 19·1 months (IQR 10·3-28·8). Progression-free survival was improved in patients assigned to the ofatumumab group (29·4 months, 95% CI 26·2-34·2) compared with those assigned to observation (15·2 months, 11·8-18·8; hazard ratio 0·50, 95% CI 0·38-0·66; p<0·0001). The most common grade 3 or higher adverse events up to 60 days after last treatment were neutropenia (56 [24%] of 237 patients in the ofatumumab group vs 23 [10%] of 237 in the observation group) and infections (31 [13%] vs 20 [8%]). 20 (8%) of 237 patients in the ofatumumab group and three (1%) of 237 patients in the observation group had adverse events that led to permanent discontinuation of treatment. Up to 60 days after last treatment, two deaths related to adverse events occurred in the ofatumumab treatment group and five deaths related to adverse events occurred in the observation group; no deaths were attributed to the study drug. These data are important for the development of optimum maintenance strategies in patients with relapsed chronic lymphocytic leukaemia, notably in the present era of targeted drugs, many of which are to be used until progression.


Treatment of oil sands process-affected water (OSPW) using a membrane bioreactor with a submerged flat-sheet ceramic microfiltration membrane.
The release of oil sands process-affected water (OSPW) into the environment is a concern because it contains persistent organic pollutants that are toxic to aquatic life. A modified Ludzack-Ettinger membrane bioreactor (MLE-MBR) with a submerged ceramic membrane was continuously operated for 425 days to evaluate its feasibility on OSPW treatment. A stabilized biomass concentration of 3730 mg mixed liquor volatile suspended solids per litre and a naphthenic acid (NA) removal of 24.7% were observed in the reactor after 361 days of operation. Ultra Performance Liquid Chromatography/High Resolution Mass Spectrometry analysis revealed that the removal of individual NA species declined with increased ring numbers. Pyrosequencing analysis revealed that Betaproteobacteria were dominant in sludge samples from the MLE-MBR, with microorganisms such as Rhodocyclales and Sphingobacteriales capable of degrading hydrocarbon and aromatic compounds. During 425 days of continuous operation, no severe membrane fouling was observed as the transmembrane pressure (TMP) of the MLE-MBR never exceeded -20 kPa given that the manufacturer's suggested critical TMP for chemical cleaning is -35 kPa. Our results indicated that the proposed MLE-MBR has a good potential for removing recalcitrant organics in OSPW.


Immunolocalization of c-myc oncoprotein in mucinous and serous adenocarcinomas of the ovary.
Activation of c-myc oncogene has been reported in increasing numbers of human ovarian carcinomas and appears to play a role in the biologic behavior of the neoplasms. We have studied the immunohistochemical localization of p-62c-myc, the gene product of c-myc, in 44 cases of serous and mucinous cystadenoma, adenocarcinoma of low malignant potential, and invasive adenocarcinoma, using a monoclonal antibody raised to a synthetic human p62c-myc sequence (Myc 1-6E10). Both serous and mucinous cystadenomas demonstrated a higher frequency of nuclear localization than did carcinomas, which showed much greater cytoplasmic staining, while tumors of low malignant potential showed an intermediate pattern. However, the observed differences did not reach statistical significance. No significant correlation was observed between intracellular localization patterns of p62c-myc and histologic and nuclear grades and mitotic activity in the cases of carcinoma. Great care should be taken in the interpretation of immunohistochemical analysis of oncogene products, especially when attempting to correlate the findings with biologic tumor behavior.


Altered molecular species of human interferon produced in the presence of inhibitors of glycosylation.
The inhibitors of glycosylation, 2-deoxy-D-glucose or D-glucosamine, inhibit the synthesis of biologically active interferon in human FS-4 fibroblast cultures stimulated with polyinosinate-polycytidylate. Interferon synthesized in the presence of partially inhibitory concentrations of 2-deoxy-D-glucose or D-glucosamine were found to differ from interferons made in control cultures in some physical properties. Interferons synthesized in the presence of either inhibitor had a diminished charge heterogeneity demonstrable by iso-electric focusing. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, control interferon activity formed a single peak with the apparent molecular weight of 20,000, whereas interferons from cultures treated with either inhibitor could be resolved into two distinct molecular weight components, one of which was smaller than the interferon synthesized in control cultures.


The extensor assembly in two species of opossum, Philander opossum and Didelphis marsupialis.
In considering primate and hominoid phylogeny, the fundamental position assigned to opossums is explained partially by the characteristic morphology of their hands and feet. One of the main functional features of the human hand is the ability to make a stabilized arch of the finger. Because the extensor assembly plays a key role in establishing an arched finger, the extensor systems of the digits of both the hands and feet were studied in two species of opossum, Philander opossum and Didelphis marsupialis. In the foot, two extensor tendons join in each toe to form one tendinous plate, which inserts onto the base of the second phalanx. Lumbricals join this plate along the tibial side, and interosseus insertions are found, although a true interosseus wing is lacking. At the proximal interphalangeal level, a terminal tendon takes its origin from this tendinous plate. This terminal tendon is oval in cross-section and contains elastic structures. Oblique bands arise from this terminal tendon and run proximally along the proximal interphalangeal joint inserting onto the base of the first phalanx. There are elastic structures in the flexor tendon on the dorsal side near its site of insertion. In the hand, the main extensor tendons are arranged differently and the interossei contribute substantially to the extensor assembly. Otherwise, the extensor assembly of the hands and feet are quite similar. The function of the so-called paratendinous intravaginal flexors is discussed as are evolutionary aspects of the extensor assembly.


Increasing prevalence of gestational diabetes mellitus when implementing the IADPSG criteria: A systematic review and meta-analysis.
Quantify the proportional increase in gestational diabetes (GDM) prevalence when implementing the new International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria compared to prior GDM criteria, and to assess risk factors that might affect the change in prevalence. A systematic review and meta-analysis was performed of cohort and cross-sectional studies between January 1, 2010 to December 31, 2018 among pregnant women with GDM using IADPSG criteria compared to, and stratified by, old GDM criteria. Web of science, PubMed, EMBASE, Cochrane, Open Grey and Grey literature reports were included. The relative risk for each study was calculated. Subgroup analyses were performed by maternal age, body mass index, study design, country of publication, screening method, sampling method and data stratified according to diagnostic criteria. Thirty-one cohort and cross-sectional studies with 136 705 women were included. Implementing the IADPSG criteria was associated with a 75% (RR 1.75, 95% CI 1.53-2.01) increase in number of women with GDM with evidence of heterogeneity. The IADPSG criteria increase the prevalence of GDM, but allow movement towards more homogeneity. More studies are needed of the benefits, harms, psychological effects and health costs of implementing the IADPSG criteria.


Population cycles are highly correlated over long time series and large spatial scales in two unrelated species: greater sage-grouse and cottontail rabbits.
Animal species across multiple taxa demonstrate multi-annual population cycles, which have long been of interest to ecologists. Correlated population cycles between species that do not share a predator-prey relationship are particularly intriguing and challenging to explain. We investigated annual population trends of greater sage-grouse (Centrocercus urophasianus) and cottontail rabbits (Sylvilagus sp.) across Wyoming to explore the possibility of correlations between unrelated species, over multiple cycles, very large spatial areas, and relatively southern latitudes in terms of cycling species. We analyzed sage-grouse lek counts and annual hunter harvest indices from 1982 to 2007. We show that greater sage-grouse, currently listed as warranted but precluded under the US Endangered Species Act, and cottontails have highly correlated cycles (r = 0.77). We explore possible mechanistic hypotheses to explain the synchronous population cycles. Our research highlights the importance of control populations in both adaptive management and impact studies. Furthermore, we demonstrate the functional value of these indices (lek counts and hunter harvest) for tracking broad-scale fluctuations in the species. This level of highly correlated long-term cycling has not previously been documented between two non-related species, over a long time-series, very large spatial scale, and within more southern latitudes.


Effects of repeated as compared to single aggressive confrontation on nociception and defense behavior in C57BL/6 and DBA/2 mice.
Behavioral reactions (submissive postures, escape, immobility, activity, locomotion) in C57BL/6 and DBA/2 test mice were recorded during single (50 bites) or three repeated (3 X 50 bites, separated by 24 hr) aggressive confrontations, as well as during a nonaggressive confrontation 24 hr after the last aggressive confrontation with opponents of the opposite strain. Nociception (hot plate response latency) was measured 1 min after aggressive or nonaggressive confrontations. During repeated aggressive confrontation, DBA mice reacted with a stable pattern of escape and analgesia, whereas C57 mice failed to develop an analgesic response and changed their behavioral defense strategy during repeated aggressive confrontations (decrease of escape, increase of defensive upright). The conditioned display of submission and of escape behavior during nonaggressive confrontation did not change as a function of earlier repeated aggressive confrontations in DBA mice, while C57 mice showed a significant increase of defensive upright postures and immobility. Conditioned analgesia was not observed after nonaggressive confrontations. The results point toward a dissociation between attack-elicited behavior and antinociception and suggest that encounter-induced analgesia may influence the processing of aversive experience.


Superior voice recognition in a patient with acquired prosopagnosia and object agnosia.
Anecdotally, it has been reported that individuals with acquired prosopagnosia compensate for their inability to recognize faces by using other person identity cues such as hair, gait or the voice. Are they therefore superior at the use of non-face cues, specifically voices, to person identity? Here, we empirically measure person and object identity recognition in a patient with acquired prosopagnosia and object agnosia. We quantify person identity (face and voice) and object identity (car and horn) recognition for visual, auditory, and bimodal (visual and auditory) stimuli. The patient is unable to recognize faces or cars, consistent with his prosopagnosia and object agnosia, respectively. He is perfectly able to recognize people's voices and car horns and bimodal stimuli. These data show a reverse shift in the typical weighting of visual over auditory information for audiovisual stimuli in a compromised visual recognition system. Moreover, the patient shows selectively superior voice recognition compared to the controls revealing that two different stimulus domains, persons and objects, may not be equally affected by sensory adaptation effects. This also implies that person and object identity recognition are processed in separate pathways. These data demonstrate that an individual with acquired prosopagnosia and object agnosia can compensate for the visual impairment and become quite skilled at using spared aspects of sensory processing. In the case of acquired prosopagnosia it is advantageous to develop a superior use of voices for person identity recognition in everyday life.


Surgical Resection of Nasal Chondroma via open Rhinoplasty Approach: A rare case Presentation and Review of Literature.
Chondromas are benign tumors composed of mature hyaline cartilage tissue with well-defined boundaries that are commonly localised in the extremities with very few cases described in the head and neck region. We present a case of 57-year-old patient who consulted a specialist for an examination due to a change in the tip of the nose that persisted for the past 2 years. The clinical exam revealed a firm, tumor-altered tip of the nasal pyramid, with hyperemia of the skin above the mass. Biopsy was taken under local anesthesia; the histopathology analysis indicated a mesenchymal tumor producing the chondroid matrix suggestive of nasal type chondroma. Computerized tomography showed an ovoid, moderately inhomogeneous, sharply limited formation measuring 21 × 18 × 24 mm present mediosagitally at the top of the nasal pyramid. After preoperative preparation, the surgery was performed by open rhinoplasty approach. Tumor was completely excised with reconstruction of nasal septum and alar cartilage. The online version contains supplementary material available at 10.1007/s12070-023-03661-0.


Two-stage hepatectomy and associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) in treating liver metastases of rectal cancer: a case report.
An innovative approach, called associated liver partition and portal vein ligation for staged hepatectomy(ALPPS), has made possible a marked increase in future liver remnant (FLR) volume over a short period of time, thus permitting extended hepatectomy. This report describes ALPPS in a 63-year-old male patient with rectal cancer and synchronous multiple liver metastases. The primary lesion was resected, followed by chemotherapy. We had planned to completely resect the metastases in both liver lobes, but CT volumetry revealed a very small FLR (364 ml, 29% of the total liver volume, 0.61% of total body weight). His indocyanine green retention rate at 15 minutes was 12.7%. Because of the risk of tumor progression in the interim, we performed ALPPS. During the first stage, the tumor in segment 3 was resected, the right lobe was mobilized, the liver was partitioned, and the right portal vein was ligated. The right hepatic artery, duct and vein were secured with vessel loops. CT on postoperative day 6 showed sufficient FLR increase (from 364 ml to 573 ml, or from 0.61% to 0.96% of total body weight) and ICGR15 improvement to 3.4%. The second stage of ALPPS was on postoperative day 7, completing resection of the metastases. The patient recovered well and was discharged 21 days after the second step. The ALPPS approach has many advantages, but it lacks evidence of long-term results. Considering the high mortality and morbidity rates of ALPPS, it is essential to evaluate its risks and benefits in individual patients and determine the strict criteria for this surgical method. ALPPS procedure rapidly increases FLR, permitting extended hepatectomy for patients with initially insufficient FLR.


Genetic structure of an endangered Portuguese semiferal pony breed, the Garrano.
The present study intends to survey the genetic variability of an endangered semiferal Portuguese native pony breed, the Garrano. Thirteen microsatellite markers were examined in 277 animals born in 1998, belonging to eight subpopulations corresponding to eight northern Portuguese geographic regions. Mean heterozygosity (H(o)) in the Garrano breed was 0.732, ranging from 0.531 to 0.857 across subpopulations. Allelic frequencies and diversity differed significantly between regions, suggesting the existence of genetic differentiation within the breed confirmed by the population differentiation estimator F(ST). Allele sharing genetic distance (Dps) was used to determine the relationship between the analyzed subpopulations, some of which are diverging significantly from the others. Relationships among six Iberian horse breeds (including the Garrano) were assessed through the restricted maximum likelihood method, which clusters the Garrano with another Celtic pony, the Spanish Asturcon, traditionally bred in geographical continuity with the Garrano. Results reveal a statistically significant deficit of heterozygotes within the Garrano breed (F(IT) = 0.031, p < 0.05). Regular monitoring should therefore be implemented so that the effect of genetic drift within subpopulations, enhanced by inbreeding, may be successfully minimized.


The content of phenolic compounds and radical scavenging activity varies with carrot origin and root color.
The contents of phenolic compounds and radical scavenging activities were assessed in a carrot collection comprising 35 cultivars, landraces and breeding populations. The accessions originated from various world regions and they represented Eastern and Western carrot gene pools. In two-year field trial carrot roots of orange, red, yellow, white and purple color were cultivated, freeze-dried and analyzed for phenolic content by Folin-Ciocalteu assay and UV/Vis assay. Radical scavenging activity in the extracts was determined with a stable DPPH radical. Carrots developing purple roots possessed on average 9 times more phenolics than roots of other colors. Furthermore, they were rich in anthocyanins that caused very high antiradical activity. Red carrots showed higher antioxidant activity than orange, yellow and white carrots and in the season of lower rainfall they accumulated higher amounts of phenolic compounds. Carrots of Asian origin belonging to Eastern gene pool were more often purple or red and richer in phenolics and had higher antiradical activity than those from the Western gene pool with mainly orange roots.


Primary papillary serous neoplasia of the peritoneum: a clinicopathologic and ultrastructural study of eight cases.
The well-documented but rare primary papillary serous peritoneal tumors are difficult problems for the pathologist and the clinician. Because of their unusual location, these tumors are often classified as mesothelioma or advanced ovarian carcinoma. In this study, we report the clinicopathologic features of eight primary peritoneal serous papillary tumors and compare their histologic and ultrastructural features to 12 serous ovarian tumors and 16 epithelial mesotheliomas (two peritoneal and 14 pleural). The eight peritoneal serous papillary tumors occurred in women aged 19 to 75 years; two were serous tumors of low malignant potential (borderline) and six were serous carcinomas. The tumors were located in the mesosalpinx, left pelvis, omentum, and/or surface of the ovary. The two patients with borderline neoplasms had long disease-free survival (11 years and 20 years), while three of the four patients with carcinoma with more than 1 year of follow-up died of disease. The peritoneal serous papillary tumors were morphologically identical to serous ovarian tumors of equivalent grade. Well-differentiated papillary structures with distinct fibrovascular cores and one or several layers of columnar, crowded cells, dense overlapping nuclei with a long axis perpendicular to the surface of the papillary cores, and numerous psammoma bodies were features of the peritoneal and ovarian serous tumors. In contrast, the tubulo-alveolar, solid, or poorly defined papillary structures lined by well-spaced polygonal to cuboidal cells with abundant cytoplasm, absence of nuclear polarity, and infrequent psammoma bodies characterized the mesotheliomas. Epithelial mucin and carcinoembryonic antigen (CEA) immunoreactivity, when present, supported a diagnosis of serous tumor in these generally mucin-poor and CEA-negative neoplasms. Ultrastructurally, the cells of serous tumors had slender, straight microvilli of variable length interspersed with or without cilia, while the nonciliated cells of mesothelioma had long, exuberant, wavy microvilli. The morphologic and clinical features of the peritoneal papillary serous tumors are distinctive enough to warrant their separation from mesotheliomas.


Polyketides from the endolichenic fungus Eupenicillium javanicum and their anti-inflammatory activities.
Seven undescribed polyketides javanicols A-E, 5-epi-citreoviridin and 5-epi-isocitreoviridin, together with five known compounds, were isolated from the endolichenic fungus Eupenicillium javanicum. The structures of these polyketides were determined by means of extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations and gauge-independent atomic orbital (GIAO) NMR shift calculations. These compounds were evaluated for potential anti-inflammatory activity against LPS-activated RAW 264.7 cells. Javanicol E and (+)-terrein displayed moderate inhibitory effects on NO production, with IC50 values of 17.00 and 13.46 μM, respectively.


Human hypoxanthine-guanine phosphoribosyltransferase: a single nucleotide substitution in cDNA clones isolated from a patient with Lesch-Nyhan syndrome (HPRTMidland).
We have determined the molecular basis for hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency in a patient, J.H., with Lesch-Nyhan syndrome. Radioimmunoassay of lysates of erythrocytes or cultured B-lymphoblasts showed that this patient had no detectable HPRT enzyme activity or HPRT protein. HPRT-specific mRNA levels were normal by Northern analysis. We created a cDNA library from mRNA isolated from cultured lymphoblasts derived from this patient. Nucleotide sequencing of full-length HPRT cDNA clones revealed a single nucleotide (nt) substitution: a T-to-A transversion at nt 389. We have designated this variant HPRTMidland. The predicted amino acid (aa) substitution in HPRTMidland is a valine to aspartic acid at aa 130. This substitution is within 2 aa of the amino acid substitution in a previously defined HPRT variant, HPRTAnn Arbor. Both mutations are within a highly conserved sequence in the putative 5-phosphoribosyl-1-pyrophosphate-binding domain. The amino acid substitution in HPRTMidland causes a significant perturbation in the predicted secondary structure of this region. The HPRTMidland mutation affects a different domain of HPRT than the HPRTFlint mutation located at 167 nt away.


Ouabain induced seizures: site of production and response to anticonvulsants.
Ouabain, an inhibitor of Na+ -K" -ATP'ase, has been administered intraventricularly to rats to study the effect of impairment of membrane transport mechanisms on the genesis of seizures. Running and leaping seizures occur rapidly after injection of ouabain in a low volume (10 microliter) when the maximal uptake of ouabain (39.8%) is the hippocampus. Generalized clonic-tonic seizures are induced by higher volume injections (50 microliter) associated with wider distribution of ouabain, including the cerebellum and brainstem. Ouabain was injected into cerebral cortex, caudate nucleus, dorsal hippocampus, fastigeal nucleus, ventrolateral mesencephalic reticular formation and cerebellar cortex. The cerebellar injections produced both running and leaping and generalized clonic-tonic seizures. It is suggested that this results from decreased inhibitory effect of vermal and paravermal Purkinje cells on intra-cerebellar nuclei, which alters cerebellar influence on the reticular formation and the limbic system. Diphenylhydantoin, phenobarbitone, phenacemide, carbamezepine and clonazepam but not ethosuximide are effective against generalized clonic-tonic seizures, suggesting that this is a model for "grand mal" but not "petit mal" seizure mechanisms. It is furthermore suggested that running and leaping are subcortical, probably limbic, seizures that are most relevant as a model for temporal lobe seizures.


Neuroretinitis associated with herpes simplex encephalitis in an adult.
A 48-year-old man who died of herpes simplex encephalitis had a bilateral papillitis at autopsy. Intranuclear inclusion bodies were especially numerous within the ganglion cells and inner nuclear layer of the macula and consisted of typical virions by electron microscopy. Contiguous spread from the brain to the eyes may have occurred via the optic nerves. Clinically, the disk and retinal changes were misinterpreted as being caused by papilledema. Papillitis should be included in the differential diagnosis of disk swelling in adults with suspected Herpesvirus hominis infection of the central nervous system.


Efficient femtosecond pulse generation in an all-normal-dispersion Yb:fiber ring laser at 605 MHz repetition rate.
We report a 1030 nm-wavelength Yb:fiber laser that produces the shortest/direct output pulse duration (502 fs) among all-normal-dispersion fiber lasers at the highest repetition rate (605 MHz) among the passively fundamentally mode-locked fiber lasers. The laser also exhibits an optical efficiency of 70% at CW and 65% at mode-locking modes.


Association of Physical Fitness With Pain in Women With Fibromyalgia: The al-Ándalus Project.
This population-based cross-sectional study aimed to characterize the association of different components of physical fitness with pain levels, pain-related catastrophizing, and chronic pain self-efficacy in women with fibromyalgia (FM). A total of 468 women with FM participated. The experience of pain was assessed with different tools (algometry, a numeric rating scale [revised FM impact questionnaire], a visual analog scale, and the bodily pain subscale on the Short Form 36 health survey). We also assessed pain-related catastrophizing and chronic pain self-efficacy. Physical fitness was assessed with performance-based tests (Senior Fitness Test battery and handgrip dynamometry). A standardized composite score was computed for each component of physical fitness (aerobic fitness, muscle strength, flexibility, and motor agility), and their average comprised a clustered global fitness profile. Overall, higher physical fitness was consistently associated with lower levels of pain, lower pain-related catastrophizing, and higher chronic pain self-efficacy (regardless of the pain assessment method and the fitness test evaluated). Muscle strength and flexibility were independently associated with pain (P < 0.005 for both), and participants with high muscle strength plus high flexibility (combined effect) had the lowest levels of pain in this population. Aerobic fitness and flexibility were independently associated with pain-related catastrophizing (P < 0.001 for both) and chronic pain self-efficacy (P < 0.001 for both), and participants with high flexibility plus high aerobic fitness (combined effect) had the best catastrophizing and self-efficacy profiles. Our results suggest that higher physical fitness is associated with lower levels of pain, lower pain-related catastrophizing, and higher chronic pain self-efficacy in women with FM. These results might have implications for future intervention studies in this population.


Dendritic spine pathology in schizophrenia.
Schizophrenia is a neurodevelopmental disorder whose clinical features include impairments in perception, cognition and motivation. These impairments reflect alterations in neuronal circuitry within and across multiple brain regions that are due, at least in part, to deficits in dendritic spines, the site of most excitatory synaptic connections. Dendritic spine alterations have been identified in multiple brain regions in schizophrenia, but are best characterized in layer 3 of the neocortex, where pyramidal cell spine density is lower. These spine deficits appear to arise during development, and thus are likely the result of disturbances in the molecular mechanisms that underlie spine formation, pruning, and/or maintenance. Each of these mechanisms may provide insight into novel therapeutic targets for preventing or repairing the alterations in neural circuitry that mediate the debilitating symptoms of schizophrenia.


Embolization of a large pancreatic pseudoaneurysm converted from pseudocyst (hemorrhagic pseudocyst).
Bleeding pancreatic pseudoaneurysms are a rare complication of chronic pancreatitis with a severe prognosis and high mortality. Conversion of a pancreatic pseudocyst into a pseudoaneurysm is a potentially lethal complication because, when rupture occurs, there is a high mortality rate. We describe a case of pancreatic pseudoaneurysm converted from a pseudocyst. A 57-year-old man with chronic pancreatitis and alcoholic liver cirrhosis presented with abdominal pain in the upper epigastric region. CT and a selective angiogram of the superior mesenteric artery showed a large bleeding pancreatic pseudoaneurysm. The pseudoaneurysm was successfully treated with coil embolization of the feeding artery. Endovascular trans-catheter embolization for the treatment of pancreatic pseudoaneurysms is a safe, effective and repeatable procedure with high success rates and it should be used as a treatment of choice in appropriate patients, either as a temporizing measure to control active bleeding and allow hemodynamic stabilization for a surgical procedure or as a definitive treatment.


[Current prevention and treatment strategies for osteoporosis. Fracture-oriented, effective, low side effects and inexpensive].
Osteoporosis is still an underdiagnosed and insufficiently therapied widespread disease in Germany. Of the estimated 7 million osteoporosis patients only 1.5 million receive a guideline conform diagnosis and even less receive appropriate treatment. Some 90 % of patients are provided with analgesics but only 10 % receive an effective therapy, although efficacious, well-tested and affordable medications are available. In addition, approximately one half of the patients terminate treatment after only 1 year although according to the results of recent studies the duration of therapy should be at least 3-5 years. In view of the increasing average life expectancy, a consistent management for prevention of fractures associated with osteoporosis is always most important for society, even if only for reasons of costs. Achievement of this target depends on four circumstances: clarification of the origin of osteoporosis and fractures (bone consciousness), prophylaxis of bone loss and fractures (primary prevention), consistent guideline conform diagnostics and therapy (secondary and tertiary prevention) and cooperation of all disciplines in medicine (bone is everybody's business). This article describes the current state of diagnostics (bone density measurement with dual X-ray absorptiometry, FRAX®), prophylaxis of fractures (screening program) and therapy (use of economic and effective medications with low side effects). Novel medications are already undergoing clinical testing and a "healing" of bone reduction with restoration of the normal bone structure is to be expected.


Type I IFN signalling is required for cationic adjuvant formulation (CAF)01-induced cellular immunity and mucosal priming.
Despite being in the midst of a global pandemic of infections caused by the pathogen Chlamydia trachomatis, a vaccine capable of inducing protective immunity remains elusive. Given the C. trachomatis mucosal port of entry, a formulation compatible with mucosal administration and capable of eliciting potent genital tract immunity is highly desirable. While subunit vaccines are considered safer and better tolerated, these are typically poorly immunogenic and require co-formulation with immune-potentiating adjuvants. However, of the adjuvants licensed for use in humans, very few drive robust cellular responses, a pre-requisite for protection against C. trachomatis infection. Recently, the cationic adjuvant formulations (CAF) have been shown to induce robust humoral and cellular immunity in pre-clinical models of chlamydia, malaria and tuberculosis (TB). Here, we demonstrate that CAF01 induces potent immune responses when combined with the major outer membrane protein (MOMP) of C. trachomatis following parenteral immunisation and also as part of a heterologous prime/boost regime. We show that a subcutaneous prime with CAF01-adjuvanted recombinant MOMP licenses antigen-specific immunity at distant mucosal sites which can be activated following oral antigen re-encounter in the absence of concomitant adjuvant stimulation. Finally, we shed light on the mechanism(s) through which CAF01 elicits robust antigen-specific immunity to co-formulated MOMP via type I interferon (IFN) signalling.


Genetic and epigenetic serotonergic markers predict the ability to recognize mental states.
The serotonergic (5-HT) system is related to affective and cognitive processes and explains behavioral variability in the normal and psychopathological range. For this reason, the hypothesis was put forward that genetic and epigenetic markers related to 5-HT metabolism predict individual differences in social cognitive functioning. Social cognitions are complex mental processes necessary for perceiving, interpreting and reacting to the behaviors of others. In order to test this hypothesis one of the most prominent theory of mind tasks, the reading the mind in the eye test (RMET), was administered to N = 435 participants and measures of performance were related to the functional MAO-A VNTR polymorphism (relevant for 5-HT catabolism) and to epigenetic markers in the promoter of the TPH-2 gene (relevant for 5-HT synthesis). It was postulated that genetic and epigenetic markers of high 5-HT activity are positively related to RMET performance. Results show that the MAO-A high activity allele, together with the degree of methylation at a promoter CpG site on the TPH-2 gene explain significant proportions of variance in the RMET performance even after controlling for age and sex effects. Present findings yield evidence for the importance of 5-HT for social cognition. Based on additional findings, the role of a TRP-rich diet for theory of mind functions is discussed.


The occurrence and probabilistic risk assessment of 3-MCPDEs and GEs in infant formulas from Chinese market employing Monte Carlo simulation technique.
3-monochloropropane-1,2-diol esters (3-MCPDEs) and glycidyl esters (GEs) are food contaminants and have arisen continuous attention due to their toxicity, especially towards infants. Current risk assessment of these contaminants was mostly employing deterministic approaches, lacking quantitative characterization of the likelihood, incidence, or severity of the risks involved. Herein, 3-MCPDE and GE levels in 46 representative infant formulas (IFs) from Chinese market were determined by GC-MS/MS. Then, combining the occurrence data and consumption data from China National Food Consumption Survey, the Monte Carlo simulation-based probabilistic model for risk assessment of 3-MCPDEs and GEs in IFs from Chinese market was established. The results showed that all P90 (90th percentiles) hazard quotient values were below 1, demonstrating 3-MCPDEs didn't pose health risks to most populations aged 0-36 months old. However, for 0-12 months old groups, P10 (10th percentiles) margin of exposure values were all below 25000, indicating GEs may pose potential risks to 10% of this group. Uncertainty analysis revealed that the probabilistic model had considered uncertainties of model input and distribution, and realized refined assessment. This study is the first report on probabilistic assessment of 3-MCPDEs and GEs in IFs, which also provided references for the formulation of related regulatory limits in China.


Competing barnacle species with a time dependent reproduction rate.
A simple competition model with time varying periodic coefficients, in which two species use different reproduction strategies, is explored in this paper. The two species considered comprise a native species which reproduces once a year over a short time period and an invasive species which is capable of reproducing throughout the entire year. A monotonicity property of the model is instrumental for its analysis. The model reveals that the time difference between the peak of reproduction for the two species is a critical factor in determining the outcome of competition between these species. The impact of climate change and an anthropogenic disturbance, comprising the creation of additional substrate, is also investigated using a modified model. The results of this paper describe how climate change will favour the invasive species by reducing the time period between the reproductive peaks of the two species and how the addition of new substrates is likely to endanger a small population of either of the two species, depending on the timing of the introduction of the substrates.


The prebiotic effect of CPP-ACP sugar-free chewing gum.
To determine if chewing gum containing casein phosphopeptide stabilised amorphous calcium phosphate (CPP-ACP) promoted an increase in the abundance of Streptococcus sanguinis and other species associated with dental health in supragingival plaque in a clinical study. Nineteen participants were recruited for a three-leg cross-over, randomised, controlled clinical trial. Participants chewed a sugar-free gum with or without CPP-ACP six times daily for 20 min over two weeks. The study also involved no gum chewing (no gum) for the same two week period. Participants were randomly assigned to one of the test gums or no gum for each intervention period. Participants abstained from oral hygiene and had washout periods of two weeks between intervention periods. After each intervention period, supragingival plaque was collected and analysed for bacterial composition by sequencing the V4 variable region of the 16S rRNA gene. Data were analysed using a linear mixed model. The CPP-ACP gum intervention produced a significant (p < 0.01) increase in the proportions of S. sanguinis (112%), as well as the commensal species Rothia dentocariosa (127%), Corynebacterium durum (80%) and Streptococcus mitis (55%) when compared with the no gum intervention. All the species that were promoted by the CPP-ACP gum are known to possess one or both of the alkali-producing enzymes arginine deiminase and nitrate reductase. This clinical study demonstrated that chewing a sugar-free gum containing CPP-ACP promoted prebiosis by significantly increasing the proportion of S. sanguinis and other health-associated bacterial species in supragingival plaque. Regular chewing of CPP-ACP sugar-free gum increases the proportions of health-associated commensal species in supragingival plaque to promote prebiosis and oral homeostasis.


Introduction of a CD40L genomic fragment via a human artificial chromosome vector permits cell-type-specific gene expression and induces immunoglobulin secretion.
Gene therapy using cDNA driven by an exogenous promoter is not suited for genetic disorders that require intrinsic expression of a transgene, such as hyperimmunoglobulin (Ig)M syndrome (HIGM), which is caused by mutations in the CD40L gene. The human artificial chromosome (HAC) vector has the potential to solve this problem, because it can be used to transfer large genomic fragments containing their own regulatory elements. In this study, we examined whether introduction of a genomic fragment of CD40L via the HAC vector permits intrinsic expression of the transgene and has an effect on immunoglobulin secretion. We constructed an HAC vector carrying the mouse CD40L genomic fragment (mCD40L-HAC) in Chinese hamster ovary (CHO) cells and transferred the mCD40L-HAC vector into a human CD4-positive active T-cell line (Jurkat) and a human myeloid cell line (U937) via microcell-mediated chromosome transfer (MMCT). The mCD40L-HAC vector permits mCD40L expression in human active T cells but not in human myeloid cells. The mCD40L-HAC also functions to stimulate mouse B cells derived from CD40L(-/-) mice, inducing secretion of IgG. This study may be an initial step toward the therapeutic application of HAC vectors for intrinsic expression of genes, a potential new direction for genome-based gene therapy.


Suicide in Newfoundland and Labrador: a linkage study using medical examiner and vital statistics data.
To examine suicide epidemiology in Newfoundland and Labrador from 1997 to 2001. Data from the Office of the Chief Medical Examiner (CME) were linked with data derived from the Canadian Vital Statistics Death Database. Ninety-five percent confidence intervals (CI) were calculated to assess variation of rates. We used the chi-square test to compare categorical data. The CME recorded 225 suicide deaths, compared with 187 in the Canadian Vital Statistics Death Database. Most deaths not coded as suicide in the national database were coded as accidental. Using the CME data, the overall suicide rate was 9.5/100000, aged 10 years and older. The rate among males (15.8/100 000, 95% CI, 10.7 to 20.8) was almost 5 times that of females (3.3/100000; 95% CI, 1.0 to 5.5). Age-standardized rates decreased over the study period, from 10.9 to 8.0/100000; however, the difference was not significant. The proportionate mortality ratio for suicide deaths was highest among those aged 10 to 19 years (20.0%) and decreased with age. The suicide rate was highest among those aged 50 to 59 years. The rate for unpartnered individuals (17.0/100000, 95% CI, 10.7 to 23.0) was significantly higher, compared with partnered individuals (5.1/100000; 95%CI, 2.5 to 7.8). Males used more violent methods than females. Suicide was significantly higher in Labrador (27.7/100000, 95% CI, 18.4 to 37.0), an area with a higher Aboriginal population, compared with the island of Newfoundland (8.5/100000, 95% CI, 7.3 to 9.7). Psychiatric illness was the most common predisposing factor. Suicide deaths are highest among males, unpartnered individuals, and individuals with psychiatric disorders.


The Role of Ursodeoxycholic Acid in Acute Viral Hepatitis: an Evidence-based Case Report.
to review the role of ursodeoxycholic acid in acute viral hepatitis. following literature searching according to the clinical question on Pubmed and Cochrane Library. After filtered with our inclusion and exclusion criteria, one meta-analysis and two randomized clinical trials are obtained. Through critical appraisal, it was concluded that the articles meet the criteria for validity and relevance. the article found that there is a positive effect of ursodeoxycholic acid on the activity of serum transaminases and cholestasis indexes. However, there is insufficient evidence to support or to refute effects of ursodeoxycholic acid on disease's course as well as the viral load. better method of clinical trials are needed to obtain a valid and applicable result for daily practice.


Percutaneous treatment of hydatid cysts (Echinococcus granulosus).
A new method called PAIR (Puncture-Aspiration of cyst contents--Injection of hypertonic saline solution--Reaspiration) was used as a percutaneous treatment of hydatid cysts. In 37 patients, 120 cysts were punctured. All patients had not been considered surgical candidates. The cysts were localized in the liver, peritoneum, spleen, kidneys, muscles, and bones. In 70% of patients, good results were obtained. Recurrence occurred in 5 of 120 cysts, all at the beginning of our experience when a low concentration of sodium chloride solution was injected. Moderate allergic reactions occurred during seven cyst aspirations. No anaphylactic shock, sudden deaths or dissemination of cyst contents were observed.


Incorporation of ZrO2 particles in the oxide layer formed on Mg by anodizing: Influence of electrolyte concentration and current modes.
The objectives of the present study are to ascertain, particle incorporation during the initial stages of microarc oxidation (MAO), feasibility of increasing the level of particle incorporation through manipulation of process variables and, the use of MgO-ZrO2 composite coatings either as a pre-treatment or as a post-treatment for MAO coated Mg. Anodic oxide coatings were prepared using 0.3M NaOH+15g/l ZrO2 and 3M NaOH+15g/l ZrO2 at 10V under direct current, pulsed current (PC) unipolar and PC bipolar modes. MAO coatings were prepared using 5g/l NaOH+15g/l Na2SiO3 at 250V under direct current mode for 2min. The study reveals that it is possible to incorporate ZrO2 particles in the anodic oxide layer, suggesting such a possibility during the initial stages of MAO. When the MgO-ZrO2 composite coating is used as a pre-treatment, it helps to reduce the size and density of the pores of the MAO coatings and increased the corrosion resistance. When it is used as a post-treatment, lamellar shaped Mg(OH)2 with a very high surface area is formed on the surface, which would be beneficial to impart a better bioactivity and to facilitate immobilization of biomolecules.


Reproducibility of intra-operative measurement of the mechanical axes of the lower limb during total knee replacement with a non-image-based navigation system.
The restoration of a normal mechanical axis of the lower limb following total knee prosthesis (TKP) depends on the accuracy of the intra-operative measurement of the femoro-tibial angle. We have studied the reproducibility of intra-operative measurement of the coronal mechanical femoro-tibial axis with the OrthoPilot (Aesculap, Tuttlingen, Germany) non-image-based navigation system. A consecutive series of 20 TKP (Aesculap SEARCH Evolution prosthesis) implanted by the same surgical team of two senior orthopedic surgeons was analyzed. They used a non-image-based navigation system that allows the mechanical axes of the femur and tibia to be defined with a kinematic analysis. The operating surgeon and assistant surgeon performed the kinematic analysis twice and once, respectively, and measured coronal mechanical femoro-tibial angles in maximal extension and at 90 degrees flexion without varus or valgus stress. The mean intra-observer variation in the measurement of the coronal mechanical femoro-tibial angle in maximal extension was 0.1 degrees (SD = 0.7 degrees). The mean intra-observer variation in the measurement of the coronal mechanical femoro-tibial angle at 90 degrees of knee flexion was 0.2 degrees (SD = 0.6 degrees). The mean inter-observer variation in the measurement of the coronal mechanical femoro-tibial angle in maximal extension was 0.1 degrees (SD = 0.7 degrees). The mean inter-observer variation in the measurement of the coronal mechanical femoro-tibial angle in maximal extension was 0.0 degrees (SD = 0.6 degrees). There were no significant differences and a high correlation between all paired intra- and inter-observer measurements. This system allows high reproducibility of the intra-operative measurement of the mechanical axes of the lower limb by a non-image-based kinematic registration of the hip, knee and ankle centers.


Interactions between coral propagules in aquarium and field conditions.
The effects of intraspecific and interspecific interactions between three species of scleractinian coral micro-colonies, namely Lithophyllon undulatum, Turbinaria mesenterina and Platygyra sinensis were evaluated for their survivorship, tissue loss and growth in both field (in-situ) and aquarium (ex-situ) conditions over 12 weeks. Regardless of environmental conditions and interactions, L. undulatum survived better (91.7 ± 6.2%) than T. mesenterina (75.0 ± 25.0%) and P. sinensis (60.4 ± 39.5%). Similarly, L. undulatum registered the lowest tissue loss (0.5 ± 0.7%) as compared to T. mesenterina (14.3 ± 19.4%) and P. sinensis (22.0 ± 30.0%). However, P. sinensis gained more weight (3.2 ± 5.2 g) than either T. mesenterina (2.7 ± 2.4 g) or L. undulatum (0.8 ± 1.1 g). In both environments, all three species in intraspecific interaction generally had higher survivorship, lower tissue loss and better growth than those in interspecific interaction except the latter in in-situ conditions had a twofold increase in growth (5.8 ± 3.7 g) than the former in-situ conditions (2.8 ± 3.7 g). Hence, all three species are potentially suitable for transplantation and mariculture except perhaps for P. sinensis which performed poorly in ex-situ conditions. Corals can be transplanted either with different colonies of the same species or together with other coral taxa. This study demonstrated that L. undulatum should be transplanted between T. mesenterina and P. sinensis for optimal growth and survival.


Influence of lactate and acetate salt adaptation on Salmonella Typhimurium acid and heat resistance.
The aim of the present study was to determine the survival of Salmonella Typhimurium adapted with sodium lactate (NaL), potassium lactate/sodium acetate mixture (KL/NaA) or sodium acetate (NaA) in simulated gastric fluid (SGF) and during heat treatment. NaL-, KL/NaA- and NaA-adapted cells were prepared by incubating in tryptic soy broth (TSB) containing these salts at 5, 5 and 3% (w/v) concentration levels, respectively, for 24 h at 37 °C. The Baranyi model was used to compare the growth kinetic parameters of adapted cells. The acid and heat resistance of adapted cells were determined by incubating in SGF (pH 2.04) at 37 °C and in TSB at 55.8, 57.8 and 59.8 °C, respectively. Adapted cells had significantly (P < 0.05) longer lag phase duration (LPD) and slower maximum growth rate (MGR) than non-adapted cells. The acid resistance of KL/NaA-adapted cells was not significantly (P > 0.05) different from that of non-adapted cells. NaL-adapted cells were more susceptible to the low pH environment, whereas NaA-adapted cells showed enhanced acid resistance compared to non-adapted and other adapted cells. Unlike acid resistance, both NaL- and NaA-adapted cells showed enhanced heat resistance with increased D-values, regardless of treatment temperatures. Thus, this study indicates that adaptation of S. Typhimurium to 5% NaL or 3% NaA could enhance their ability to survive thermal processes or in the human stomach, possibly increasing the risk of Salmonella outbreaks.


Platycodin D induces apoptotic cell death through PI3K/AKT and MAPK/ERK pathways and synergizes with venetoclax in acute myeloid leukemia.
Acute myeloid leukemia (AML) is a highly heterogeneous and rapidly progressive hematopoietic neoplasm characterized by frequent relapses and variable prognoses. The development of new treatment options, therefore, is of crucial importance. Platycodin D (PD) is a triterpenoid saponin, extracted from the roots of the traditional Chinese herbal medicine Platycodon grandiflorum (Jacq.) A. DC., which has been reported to exhibit therapeutic potential against a broad range of cancers. Although the effects of PD on AML remain unclear, in the present study, we observed a concentration-dependent reduction in the viability of multiple human AML cell lines in response to treatment with PD. In addition to triggering mitochondria-dependent apoptosis via the upregulation of BAK and BIM, treatment with PD also induced cell cycle arrest at the G0/G1 phase. Western blot analyses revealed marked suppression of the phosphorylation of protein kinase B (AKT), glycogen synthase kinase-3β, ribosomal protein S6, and extracellular signal-regulated kinase (ERK) by PD, in turn implying the participation of the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/ERK pathways. Pre-incubation with LY294002, MK2206, AR-A014418, or U0126 was consistently found to significantly aggravate PD-induced inhibition of viability. Additionally, PD combined with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax elicited synergistically enhanced cytotoxic effects. The anti-leukemic activity of PD was further validated using primary samples from de novo AML patients. Given the results of the present study, PD may be a potent therapeutic candidate for the treatment of AML.


Markedly reduced blood pressure responsiveness in endotoxemic rats; reversal by neuropeptide Y.
This study in conscious normotensive rats was performed to assess the effect of the vasoconstrictor peptide, neuropeptide Y (NPY), on blood pressure responsiveness to exogenous norepinephrine in endotoxaemia. NPY and endotoxin were infused at doses which had no effect on blood pressure, whether given alone or in combination. Endotoxin markedly reduced the pressor responses to bolus injections of norepinephrine. However, blood pressure responsiveness could be enhanced by infusing NPY simultaneously with the endotoxin. It is suggested that low dose NPY infusions may be clinically useful in reversing the reduced vascular responsiveness to pressor amines in shock.


Corrigendum to "Transferrin-guided intelligent nanovesicles augment the targetability and potency of clinical PLK1 inhibitor to acute myeloid leukemia" [Bioact. Mater. 21 (March 2023) 499-510].
[This corrects the article DOI: 10.1016/j.bioactmat.2022.08.032.].


Nucleolus contains signal molecules that constitute membrane-nucleolus linked pathway.
Since there have been very few studies on nucleolar signaling, an attempt was made to establish nucleolar signal pathways which link the cell membrane to the nucleolus for the transfer of extracellular signals. Two pathways were studied. One was the G alpha s mediated cAMP pathway where two signal molecules were yielded, including RII and protein kinase A. The other was the G alpha q mediated DAG/IP3 pathway which yields two signals including protein kinase C and IP3/Ca2+. By the studying isolated nucleoli from resting liver, regenerating liver or weak carcinogen thioacetamide treated liver, it was possible to detect protein kinase A (PKA), protein kinase C (PKC) and RII subunits. In addition, CK2 was detected. It was found that external signals transmitted through G protein coupled receptors could reach into the nucleolus and that physical translocation of signal molecules was an integral step involved in membrane-nucleolus linked pathways. When an in vitro assay of the above signal molecules was carried out using [gamma-32P]-ATP, most kinase dependent phosphorylation was via the major CK2 (more than 95%). Therefore, it is suggested that the major CK2 dependent pathway is involved in 'house keeping' for nucleolar integrity and the minor pathways, dependent on PKA, PKC and others, are involved in subtle regulatory mechanisms such as 'extra-house-keeping' activities by nucleolar chromosomal remodeling.


Complexity of RNA from the neuronal and glial nuclei.
The unique DNA expression value in the brain nuclear RNA was much higher than those from other tissues. The origin of this high complexity of brain nuclear RNA was examined using the [3H]DNA-RNA saturation hybridization technique. RNA was extracted from the isolated neuronal and glial nuclei. The experimental results may indicate that the high complexity in the brain nuclei does not result from the summation of many cell types but only from the neuronal nuclei.