Effects of intensive blood pressure control on cognitive function in patients with cerebral small vessel disease.
This study aimed to investigate the effects of intensive blood pressure control on cognitive function in elderly patients with cerebral small vessel disease (CSVD). From May 2020 to June 2022, 140 outpatients and inpatients with CSVD and hypertension in the Department of Neurology of Beijing Shijingshan Hospital were selected. They were randomly divided into the standard and intensive blood pressure control groups, and the dosage of antihypertensive drugs was adjusted to reduce the blood pressure to the target level. The patients were followed up for 2 years. The medical records or data at "enrollment" and "2-year follow-up" were analyzed and evaluated. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function. Cranial magnetic resonance imaging was performed to evaluate lacunar infarctions (LIs) and white matter hyperintensity (WMH). Multiple linear regression was used to analyze the correlation between MMSE scores and blood pressure, WMH, and LIs. (1) The MMSE and MoCA scores in the standard group were significantly lower than those at enrollment. The WMH score in the standard group was significantly higher than that at enrollment. (2) After the 2-year follow-up, the 24-h systolic blood pressure (SBP), 24-h diastolic blood pressure (DBP), daytime mean SBP, daytime mean DBP, and nighttime mean SBP in the two groups significantly decreased, which had significant statistical significance (P < 0.05). (3) The correlation between blood pressure and MMSE score was analyzed using multiple linear regression analysis. The WMH score, LIs, 24-h SBP, and 24-h DBP were independently correlated with MMSE scores. In elderly patients with hypertension, a decrease in SBP to 126 mmHg, compared with 134 mmHg, can delay cognitive impairment as well as reduce LIs and cerebral WMH lesions in patients with CSVD.


Mechanistic studies of the reaction of Ir(III) porphyrin hydride with 2,2,6,6-tetramethylpiperidine-1-oxyl to an unsupported Ir-Ir porphyrin dimer.
Reaction of hydrido[5,10,15,20-tetrakis(p-tolyl)porphyrinato]iridium(III) (Ir(ttp)H) (1) with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) (2) at room temperature gave a 90% yield of the unsupported iridium(II) porphyrin dimer, Ir(II)(2)(ttp)(2) (3). Kinetic measurements revealed that the oxidation followed overall second-order kinetics: rate = k[Ir(ttp)H][TEMPO], k(25 °C) = 6.65 × 10(-4) M(-1). The entropy of activation (ΔS(‡) = -25.3 ± 2.5 cal mol(-1) K(-1)) and the kinetic isotope effect of 7.2 supported a bimolecular associative mechanism in the rate-determining hydrogen atom transfer from Ir(ttp)H to TEMPO.


Confidence bands in survival analysis.
Providing estimates of uncertainty for statistical quantities is important for statistical inference. When the statistical quantity of interest is a survival curve, which is a function over time, the appropriate type of uncertainty estimate is a confidence band constructed to account for the correlation between points on the curve, we will call this a simultaneous confidence band. This, however, is not the type of confidence band provided in standard software, which is constructed by joining the confidence intervals at given time points. We show that this type of band does not have desirable joint/simultaneous coverage properties in comparison to simultaneous bands. There are different ways of constructing simultaneous confidence bands, and we find that bands based on the likelihood ratio appear to have the most desirable properties. Although there is no standard software available in the three major statistical packages to compute likelihood-based simultaneous bands, we summarise and give code to use available statistical software to construct other simultaneous forms of bands, which we illustrate using a study of colon cancer. There is a need for more user-friendly statistical software to compute simultaneous confidence bands using the available methods.


Critical review of heavy metal pollution of traffic area runoff: Occurrence, influencing factors, and partitioning.
A dataset of 294 monitored sites from six continents (Africa, Asia, Australia, Europe, North and South America) was compiled and evaluated to characterize the occurrence and fate of heavy metals in eight traffic area categories (parking lots, bridges, and three types each of both roads and highways). In addition, site-specific (fixed and climatic) and method-specific (related to sample collection, preparation, and analysis) factors that influence the results of the studies are summarized. These factors should be considered in site descriptions, conducting monitoring programs, and implementing a database for further research. Historical trends for Pb show a sharp decrease during recent decades, and the median total Pb concentrations of the 21st century for North America and Europe are approximately 15 μg/L. No historical trend is detected for Zn. Zn concentrations are very variable in traffic area runoff compared with other heavy metals because of its presence in galvanized structures and crumbs of car tire rubber. Heavy metal runoff concentrations of parking lots differ widely according to their use (e.g., employee, supermarket, rest areas for trucks). Bridge deck runoff can contain high Zn concentrations from safety fences and galvanizing elements. Roads with more than 5000 vehicles per day are often more polluted than highways because of other site-specific factors such as traffic signals. Four relevant heavy metals (Zn, Cu, Ni, and Cd) can occur in the dissolved phase. Knowledge of metal partitioning is important to optimize stormwater treatment strategies and prevent toxic effects to organisms in receiving waters.


Osteophytic reaction to a polytetrafluoroethylene temporomandibular joint implant. Report of a case.
Alloplastic disk substitutes of polytetrafluoroethylene (PTFE) used in the management of late stage temporomandibular joint disease have often been accompanied by morbid tissue reactions and resultant destructive changes. Numerous clinicians have reported cases of severe radiographic and clinical bony destruction and degeneration accompanied by marked foreign body giant cell reactions in the adjacent soft tissues. The case reported here demonstrates just the opposite event. Osteophytic enlargement of the lateral portion of the zygomatic arch and glenoid fossa, with adaptation to the contours of the implant, along with severe condylar osteophytosis, was diagnosed through tomographic and CT imaging and was confirmed at surgery.


Panic disorder: response to sodium lactate and treatment with antidepressants.
Effective drugs for mental disorders have been found by serendipitous findings not supported by knowledge of psychopharmacology. Drug are assigned labels, such as "antidepressant" without knowledge that such a label delimits the utility of such agents. Many double-blind controlled studies have shown that imipramine effectively ameliorates panic attacks and agoraphobia. Epidemiological data show a relationship between Panic Disorder and Depression. Relatives of probands with Major Depression plus an Anxiety Disorder were at greater risk for both Major Depression and for an Anxiety Disorder. Panic Disorder, as a subcategory of Anxiety Disorder was associated with the greatest increased risk. Intravenous sodium lactate reliably produces anxiety attacks clinically indistinguishable from those occurring in Panic Disorder, in subjects with that disorder. Panic Disorder is characterized by response to imipramine, an epidemiological link to Affective Disorder, and is similar to panic induced by infusion of sodium lactate.


Development of real-time PCR and hybridization methods for detection and identification of thermophilic Campylobacter spp. in pig faecal samples.
To develop a real-time (rt) PCR for species differentiation of thermophilic Campylobacter and to develop a method for assessing co-colonization of pigs by Campylobacter spp. The specificity of a developed 5' nuclease rt-PCR for species-specific identification of Campylobacter jejuni, Campylobacter coli, Campylobacter lari, Campylobacter upsaliensis and of a hipO gene nucleotide probe for detection of C. jejuni by colony-blot hybridization were determined by testing a total of 75 reference strains of Campylobacter spp. and related organisms. The rt-PCR method allowed species-specific detection of Campylobacter spp. in naturally infected pig faecal samples after an enrichment step, whereas the hybridization approach enhanced the specific isolation of C. jejuni (present in minority to C. coli) from pigs. The rt-PCR was specific for Campylobacter jejuni, C. coli, C. lari, and C. upsaliensis and the colony-blot hybridization approach provided an effective tool for isolation of C. jejuni from pig faecal samples typically dominated by C. coli. Species differentiation between thermophilic Campylobacter is difficult by phenotypic methods and the developed rt-PCR provides an easy and fast method for such differentiation. Detection of C. jejuni by colony hybridization may increase the isolation rate of this species from pig faeces.


Edible and medicinal fungi breeding techniques, a review: Current status and future prospects.
Mushrooms of the edible and medicinal which are highly nutritious and environmentally friendly crops carry numerous medicinal benefits. For the abundant and high diversity of bioactive metabolites they possess, which are considered to be an important pool of bioresources. The efficient breeding technique is always a challenging task in mushrooms for obtaining better character strains, which are essential for developing healthy products and even consumption. This review comprehensively summarizes the breeding techniques applied to the edible and medicinal mushrooms. Including the traditional mutagenesis method, and even modern gene-editing breeding techniques, the effects of each method, and the comparison of each breeding technique are systematic illustrations. Strategies for mushroom breeding techniques in the future are also discussed in this review paper. With the ongoing sequencing of the mushroom genome, knowledge of the gene background of the strains and functions can be available for developing better markers for gene-editing breeding as CRISPR/Cas9 systems. Combine the metabolism engineering and in-silico tools analysis was the rational design of the novel strains. Modern physical mutagenesis techniques such as the ARTP and the combination of the other physical, and chemical breeding mutagens with cross-breeding techniques or the protoplasts fusion will also lead to superior strains for cultivation and pave the way for higher quality and yield.


Lactoferrin as an antimicrobial against Salmonella enterica and Escherichia coli O157:H7 in raw milk.
Improper storage conditions or processing of milk leads to potential spoilage and illness, due in part to temperature abuse, allowing bacteria present to grow and spoil the product. However, certain proteins naturally found in raw milk, such as lactoferrin, have reported antibacterial properties. The levels of lactoferrin required to effectively inhibit growth of pathogens have not been investigated thoroughly. This study aimed to examine various concentrations of lactoferrin as a potential biopreservative and as an antimicrobial against the common dairy pathogens Salmonella enterica and Escherichia coli O157:H7. Minimum inhibitory concentration assays were conducted on raw bovine milk in which the bacteria were exposed to varying concentrations of lactoferrin. In the raw milk system, the growth of E. coli O157:H7 was significantly decreased at levels greater than 14.05 mg/mL lactoferrin based on the reduction of tetrazolium salts. For S. enterica, only lactoferrin concentrations at or above 112.5 mg/mL in the milk resulted in reduced growth. Taken together, these results indicate that lactoferrin may have biopreservative potential. To fully examine the practicality and effectiveness of lactoferrin as an antimicrobial additive, a similar study should be conducted using additional (gram-positive) pathogens, such as Bacillus cereus and Listeria monocytogenes. If effective, lactoferrin could prolong the shelf life of dairy products and help reduce the incidence of foodborne illnesses in developing countries with limited refrigeration capability.


[Urgenturia, a logical improvement in order to better caracterize a keyword irritative symptom].
Multiple medical terms are used in the french medical literature to caracterize an urgency. However, it is a corner stone symptom of bladder overactivity, different from a normal physiological sensation. Specific tools have been designed to measure urgency but there is an essential need to give a specific and clear medical word according to other medical terms for urinary signs or symptoms. This leads to propose urgenturia as the specific medical term for urgency.


Components of predatory behaviour underlying density-dependent prey-size selection by Notiophilus biguttatus F. (Carabidae, Coleoptera).
Prey-size selection by the carabid beetle Notiophilus biguttatus F. was studied, using prey belonging to two-size-classes of the spring-tail species Orchesella cincta (L.) (Collembola). The highest values for attack readiness and success ratio of the attacks were obtained for the smaller prey animals. A model for prey-size selection was constructed in which these two parameters are included, predicting an increasing chance of incorporating large prey in the diet with declining total prey density. This prediction was tested experimentally and qualitatively confirmed. In a quantitative sense, however, the results deviated from the expectation. This was caused by a greater attack readiness of the beetles in a semi-natural environment (in which the prediction was tested) than in the artificial environment in which the parameters had been estimated. General relevance of the results, their bearing on optimal foraging theory and their ecological implications are discussed.


Estrogen receptors, progesterone receptors, and cell proliferation in human breast cancer.
The breast is a target organ for estrogens and progesterone. These hormones control several functions of the normal and abnormal mammary epithelium including cell proliferation. Most of the actions of estrogens and progesterone are mediated via specific steroid receptors, and one would expect that proliferating cells should contain estrogen receptors (ER) and/or progesterone receptors (PR). However, the correlation between receptor expression and cell proliferation is still controversial. In the present study we have examined 29 human breast cancer samples; in 17 of them we evaluated the simultaneous ER and PR localization with that of proliferating cell nuclear antigen (PCNA) and silver-stained nucleolar organizer regions (AgNORs) in a cell-by-cell study. We found that in almost 50% of the tumor biopsies examined, the cells expressing ER were significantly associated with elevated cell proliferation. In another group (38%) there were not significant differences between ER expression and cell proliferation. In only one of the samples (6%) the cells expressing ER showed lower cell proliferation. The study also revealed that in 44% of the tumors the PR expressing cells were associated with elevated cell proliferation. In a second group the PR expression was not significantly associated with cell proliferation (33% of the cases). Finally, in 22% of the samples the cells carrying PR showed lower cell proliferation. We also detected lower ER immunoreactivity in 30% of the breast cancer biopsies with one of the monoclonal antibodies against ER (antibody 1D5 directed against the A/B domain). This group of tumors was PR-negative (or very weakly positive) and had high proliferation. The presence of tumors with 'abnormal' ER proteins and displaying ER/PR significantly associated with elevated cell proliferation could have implications in human breast cancer treatment.


Heparin-binding growth factors and their receptors.
Heparin-binding growth factors modulate diverse biological activities including cellular proliferation, cellular differentiation, morphogenesis, and angiogenesis. Biochemical characterization for two members of the heparin-binding growth factor family, acidic and basic fibroblast growth factors, is extensive, while characterization of the remaining five members is forthcoming. Cell surface receptors have been identified for acidic and basic fibroblast growth factors, but little is known concerning their sites of action in vivo or the mechanisms involved in transducing the energy of growth factor binding to a biological response. An understanding of the biological basis for the diversity of the heparin binding growth factor family and the in vivo actions of these factors will prove a major challenge to future research efforts.


Surviving at high elevations: an inter- and intra-specific analysis in a mountain bird community.
Elevation represents an important selection agent on self-maintenance traits and correlated life histories in birds, but no study has analysed whether life-history variation along this environmental cline is consistent among and within species. In a sympatric community of passerines, we analysed how the average adult survival of 25 open-habitat species varied with their elevational distribution and how adult survival varied with elevation at the intra-specific level. For such purpose, we estimated intra-specific variation in adult survival in two mountainous species, the Water pipit (Anthus spinoletta) and the Northern wheatear (Oenanthe oenanthe) in NW Spain, by means of capture-recapture analyses. At the inter-specific level, high-elevation species showed higher survival values than low elevation ones, likely because a greater allocation to self-maintenance permits species to persist in alpine environments. At the intra-specific level, the magnitude of survival variation was lower by far. Nevertheless, Water pipit survival slightly decreased at high elevations, while the proportion of transient birds increased. In contrast, no such relationships were found in the Northern wheatear. Intra-specific analyses suggest that living at high elevation may be costly, such as for the Water pipit in our case study. Therefore, it seems that a species can persist with viable populations in uplands, where extrinsic mortality is high, by increasing the investment in self-maintenance and prospecting behaviours.


Close relation between cirrhosis and gallstones: cross-sectional and longitudinal survey.
Increased gallstone prevalence and incidence in cirrhosis have already been reported in different series, including a limited number of patients with cirrhosis. To evaluate the frequency of gallstones and related risk factors in a large series of patients with cirrhosis. The cross-sectional study involved 1010 patients with cirrhosis related to alcohol abuse, chronic viral infection, or miscellaneous causes (42%, 48%, and 10%, respectively) in Child class A, B, or C (48%, 36%, and 16%, respectively). In the longitudinal study gallstone development was monitored ultrasonographically in 618 patients free of gallstones at enrollment. The overall prevalence of gallstone(s) was 29.5% and increased significantly with age without differences according to sex or cause of cirrhosis. Multiple logistic regression analysis showed that only Child classes B and C were significantly related to a higher risk of gallstone (odds ratio, 1.63 for class C vs class A and 1.91 for class B vs class A; P = .001). During a mean+/-SD follow-up of 50 months+/-9 months, 141 (22.8%) of 618 patients developed gallstone(s), with an estimated cumulative probability of 6.5%, 18.6%, 28.2%, and 40.9% at 2, 4, 6, and 8 years, respectively. Multivariate analysis showed that Child class (hazard ratio, 2.8 for class C vs class A and 1.8 for class B vs class A; P = .002 and P = .001, respectively) and high-body mass index (hazard ratio, 1.31; P = .04) carried a significantly greater risk of gallstone formation. Cirrhosis per se represents a major risk factor for gallstones whose prevalence and incidence were far higher than those reported in a general population from the same area.


Interocular transfer of habituation in pigeons: mediation by tectal and/or posterior commissures.
Interocular transfer of the habituation to diffuse photic stimuli was demonstrated to be almost complete in pigeons. Birds submitted to visual Wulst ablation or supraoptic commissure lesion performed in much the same way. In contrast, when the tectal and posterior commissures were lesioned, pigeons failed to show interocular transfer of that learning process.


Triple whammy: women's perceptions of midlife mothering.
To understand women's experiences as older first-time mothers during the transition to menopause. A hermeneutic, phenomenological study exploring the lived experiences of 13 women aged 39 to 47 when they achieved first-time motherhood. Women were mothering one or more children aged 12 or younger and experiencing symptoms of perimenopause. Data were generated through two in-depth interviews with each woman. Meaning was mutually negotiated through dialogue with the women and simultaneously with the text, as well as through ongoing data analysis. Four themes emerged: Achieving First-Time Motherhood at Midlife, Intensive Mothering, Out of Sync, and Perimenopause as a State of Uncertainty. Increasingly, nurses and nurse midwives will be caring for women aged 40 and older as they navigate motherhood during the transition to menopause. Through their stories, women can share concerns they have about mothering at an older age, and the effect of perimenopausal symptoms on their mothering experiences. Nurses should offer anticipatory guidance to women who delay motherhood until midlife, provide information about the transition to menopause, and assess the older mother's level of social support. Nurses can help build capacity for support within community and professional resources, such as hospital supported mother/baby and breastfeeding support groups.


Increment thresholds of the three spectral mechanisms in the retina of the California ground squirrel (Spermophilus beecheyi).
Increment threshold (IT) functions were obtained for the electroretinogram (ERG) and for single units in the optic nerve of the California ground squirrel. The three spectral mechanisms providing input to ganglion cells in this retina were isolated and their increment thresholds to large field, long-duration stimuli were examined. Mean IT functions for the 519 nm mechanism (irrespective of unit class), the 500 nm mechanism, and the ERG all showed shallow log-log slopes between 0.52 and 0.63. The slope of the mean IT function for the 440 nm mechanism depended on the spectral character of the adapting light. When the dominant wavelength of this light was close to the peak sensitivity of the 440 nm mechanism, the mean IT function was steep (0.92), but when the dominant wavelength of the adapting light was at the cross-point of the opponent cells, the slope of the function was shallow (0.49). The difference in IT slope under these two conditions may be attributed to an additional sensitivity loss occuring at a spectrally-opponent site.


"AIR LEAK SYNDROME": An Unusual Presentation of Foreign Body in the Airway.
Spontaneous onset pneumomediastinum, pneumothorax and subcutaneous emphysema are rare presentations of a foreign body in the airway. The possible mechanism for unexplainable and non traumatic subcutaneous emphysema can be attributed to "Air leak syndrome" following inhalation of foreign body in the airway.


Long-acting parenteral drug delivery systems for the treatment of chronic diseases.
The management of chronic conditions often requires patients to take daily medication for an extended duration. However, the need for daily dosing can lead to nonadherence to the therapy, which can result in the recurrence of the disease. Long-acting parenteral drug delivery systems have the potential to improve the treatment of chronic conditions. These systems use various technologies, such as oil-based injectables, PLGA-based microspheres, and in situ forming gel-based depots, to deliver different types of drugs. The use of long-acting parenteral formulations for the treatment of chronic infections such as HIV/AIDS and tuberculosis is a recent development in the field. Researchers are also exploring the use of long-acting parenteral formulations for the treatment of malaria, with the aim of reducing dosing frequency and improving adherence to treatment. This review discusses various aspects of long-acting formulation development, including the impact of the physicochemical properties of the drug, the type of long-acting formulation, and the route of administration. The clinical significance of long-acting formulations and recent advances in the field, such as long-acting nanoformulations and long-acting products currently in clinical trials, have also been highlighted.


PAX2, PAX8, and PR are correlated with ovarian seromucinous borderline tumor with endometriosis.
Ovarian "seromucinous carcinoma" has been recently removed in 2020 5th Edition of WHO classification of Female Genital Tumors and is considered as a subtype of endometrioid carcinoma with mucinous differentiation, while "seromucinous borderline tumor" remains and exists as a distinct entity. Both diseases may be considered as no more same lineage. However, ovarian seromucinous borderline tumor (SMBT) is also one of the endometriosis-related neoplasm of ovary similar to endometrioid tumor, featuring that about 50% of ovarian SMBTs combine endometriosis. The present study was aimed to investigate whether the ovarian SMBTs are different in clinical features and molecular patterns, according to the presence of combined endometriosis. There were no statistical differences in clinical findings between two groups. There was also no significant difference in pregnancy outcomes and recurrence between two groups. In immunohistochemical patterns, there was a statistically significant difference in PAX2 and PAX8 expression between in ovarian SMBT with or without endometriosis (P = 0.016, P < 0.001). Only a few cases of ovarian SMBT with endometriosis showed expression of PAX2 and conversely, most of the cases showed expression of PAX8. PR positivity was more prominent in ovarian SMBT with endometriosis than without endometriosis (P = 0.018), although there was no difference in positive ER expression. There were no statistical differences in WT1, CK20 and CDX2 expressions between two groups. Ovarian SMBT with endometriosis did not clinically differ from that without endometriosis. However, the molecular patterns were different between two groups and ovarian SMBT with endometriosis is close to endometrioid tumor types unlike SMBT without endometriosis. Further, a direct comparison study between seromucinous borderline tumor and endometrioid borderline tumor is needed with a gene profiling study to prove their relationship.


Soft tissue sarcomas in childhood.
The authors discuss the epidemiology, pathology, clinical presentation, and treatment of rhabdomyosarcoma as well as some of the less common sarcomas of childhood and adolescence. Special focus is placed on making careful histopathologic distinction between entities and on clearly recognizing distinct clinical syndromes.


Voltage-sensing optical recording: A method of choice for high-throughput assessment of cardiotropic effects.
Voltage and calcium-sensing optical recording (VSOR and CSOR, respectively) from human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been validated for in vitro evaluation of cardiotropic effects of drugs. When compared to electrophysiological devices like microelectrode array, multi-well optical recordings present a lower sample rate that may limit their capacity to detect fast depolarization or propagation velocity alterations. Additionally, the respective sensitivities of VSOR and CSOR to different cardiac electrophysiological effects have not been compared in the same conditions. FluoVolt and Cal520 dyes were used in 96 well format on hPSC-CMs to report sodium channel block by lidocaine and propagation slowing by the junctional uncoupler carbenoxolone at three recording frequencies (60, 120 and 200 Hz) as well as their sensitivity to early and late repolarization delay. Sodium channel block led to a dose-dependent decrease of the VSOR signal rising slope that was improved by an increased sampling frequency. In contrast, the CSOR signal rising slope was only decreased at the highest concentration with no influence from the sampling rate. A similar result was obtained with carbenoxolone. Early repolarization delay by Bay K8644 showed the same effects on VSOR and CSOR signal durations while repolarization slowing by dofetilide had a significantly stronger prolongating effect on the VSOR signal at the lowest concentration. VSOR showed a higher capacity to detect sodium channel block, propagation slowing and modest late repolarization delay than CSOR. Increasing the sampling rate improved the detection threshold of VSOR for excitability and conduction velocity alterations.


Effects of beauvericin to mammalian tissue and its production by Austrian isolates ofFusarium proliferatum and Fusarium subglutinans.
Austrian isolates ofFusarium subglutinans andFusarium proliferatum were studied for their ability to produce beauvericin, moniliformin and fumonisin B1 and B2 under laboratory conditions. Analytical methodology for beauvericin was specially adapted for this task. Our analyses showed that the strains produced beauvericin up to 687 mg /kg maize and moniliformin up to 70 mg/kg. The culture ofF. proliferatum in addition produced fumonisin B1 and B2 at levels of 106 and 61 mg/kg,respectively. The preliminary toxicity experiments performed in this study clearly indicated a toxic effect of beauvericin on the contractility of mammalian smooth muscle and thus on mammalian cells.


Preventing perioperative complications in the patient with a high body mass index.
Patients with a high body mass index (BMI) are being seen more frequently in perioperative settings, and staff members must be prepared to prevent complications (eg, difficult intubation, respiratory insufficiency, positioning injuries) that occur in this patient population as a result of comorbidities. After two sentinel events occurred during a six-month period at a community hospital in northern California, a task force was created to examine issues related to the care of patients who are morbidly obese and to develop and implement policies and procedures to reduce the risk of adverse patient outcomes. Chart audit results confirm that the quality improvement project was successful; 92% of 50 charts showed inclusion of the BMI on the surgery schedule, and 94% showed inclusion of the BMI on the preoperative checklist. No positioning incidents or intubation emergencies have occurred in patients with a high BMI since January 1, 2009.


Myeloid sarcoma, chloroma, or extramedullary acute myeloid leukemia tumor: A tale of misnomers, controversy and the unresolved.
The World Health Organization classification and definition of "myeloid sarcoma" is imprecise and misleading. A more accurate term is "extramedullary acute myeloid leukemia tumor (eAML)." The pathogenesis of eAML has been associated with aberrancy of cellular adhesion molecules, chemokine receptors/ligands and RAS-MAPK/ERK signaling. eAML can present with or without synchronous or metachronous intramedullary acute myeloid leukemia (AML) so a bone marrow evaluation is always recommended. Accurate diagnosis of eAML requires tissue biopsy. eAML confined to one or a few sites is frequently treated with local therapy such as radiotherapy. About 75-90% of patients with isolated eAML will develop metachronous intramedullary AML with a median latency period ranging from 4 to 12 months; thus, patients with isolated eAML may also be treated with systemic anti-leukemia therapy. eAML does not appear to have an independent prognostic impact; selection of post-remission therapy including allogeneic hematopoietic cell transplant (alloHCT) is typically guided by intramedullary disease risk. Management of isolated eAML should be individualized based on patient characteristics as well as eAML location and cytogenetic/molecular features. The role of PET/CT in eAML is also currently being elucidated. Improving outcomes of patients with eAML requires further knowledge of its etiology and mechanism(s) as well as therapeutic approaches beyond conventional chemotherapy, ideally in the context of controlled trials.


Single-cell dissection of cellular and molecular features underlying mesenchymal stem cell therapy in ischemic acute kidney injury.
Mesenchymal stem cells (MSCs) exert beneficial therapeutic effects in acute kidney injury (AKI), while the detailed repair mechanism remains unclear. Herein, we probed the underlying mechanisms of MSC therapy in AKI by performing unbiased single-cell RNA sequencing in IRI model with/without MSC treatment. Our analyses uncovered the tubular epithelial cells (TECs) and immune cells transcriptomic diversity and highlighted a repair trajectory involving renal stem/progenitor cell differentiation. Our findings also suggested that profibrotic TECs expressing pro-fibrotic factors such as Zeb2 and Pdgfb promoted the recruitment of inflammatory monocytes and Th17 cells to injured kidney tissue, inducing TGF-β1 secretion and renal fibrosis. Finally, in addition to activating the repair properties of renal progenitor/stem cells, we uncovered a role for MSC-derived miR-26a-5p in mediating the therapeutic effects of MSCs by inhibiting Zeb2 expression and suppressing pro-fibrotic TECs and its subsequent recruitment of immune cell subpopulations. These findings may help to optimize future AKI treatment strategies.


Transient paralysis of upper extremity after percutaneous cannulation of the subclavian vein for hemodialysis.
Two cases of transient paralysis of upper extremity after percutaneous cannulation of the subclavian vein for hemodialysis are presented for the first time. Large amounts of lidocaine used, together with its deep and too lateral administration are responsible for development of this transient complication.


Detection of circulating human platelet fragments by using monoclonal antibodies against platelet glycoprotein IIb-IIIa complex.
A radioimmunoassay (RIA) for the detection of platelets and platelet fragments was developed. A sandwich of two monoclonal antibodies directed against the platelet-specific glycoprotein complex IIb-IIIa (GP IIb-IIIa) was used in this assay. A discontinuous 7.5-20% (v/v) albumin gradient was applied to separate platelets and their fragments of various sizes. In platelet suspensions fractionated in this way, we observed that particles smaller than normal platelets still carried the GP IIb-IIIa antigens. This procedure enabled us to detect platelet-derived particles in platelet-rich plasma from thrombocytopenic patients.


Differences in the ectoparasite fauna between micromammals captured in natural and adjacent residential areas are better explained by sex and season than by type of habitat.
We compared the ectoparasite fauna in 608 micromammals (chiefly 472 wood mice Apodemus sylvaticus, 63 Algerian mice Mus spretus, and 51 greater white-toothed shrews Crocidura russula) captured in natural and adjacent residential areas in spring and autumn during three consecutive years in four areas in periurban Barcelona (NE Spain). We found little support for an association of urbanization with differences in infestation by ectoparasites. Prevalence of Rhipicephalus sp. tick in wood mice and shrews was significantly higher in residential than in natural habitats, and the opposite was found for the flea Ctenophtalmus andorrensis catalanensis in shrews. Marked differences in the prevalence of the flea Leptopsylla taschenbergi amitina in wood mice between seasons were observed in natural but not in residential habitats, probably due to enhanced flea survival probabilities in the latter. However, as a rule, males were more frequently and heavily infested than females, and the prevalence was higher in autumn than in spring. Our results suggest that the ectoparasite fauna of periurban micromammals is shaped more by other factors than by habitat modification. People living in residential areas are at risk of contact with the arthropods borne by non-commensal micromammals and the pathogens transmitted by them.


Capnometry and the paediatric laryngeal mask airway.
The laryngeal mask airway (LMA), an alternative to tracheal intubation in certain situations, has gained popularity in recent years. Initially designed for use in adults it has now become available in suitable sizes for paediatric anaesthesia. The objectives of this study were to identify the preferred site of sampling the end-tidal carbon dioxide (PETCO2) with the LMA and to determine the accuracy of this recording when compared with arterial CO2 (PaCO2). We studied 30 healthy children, age one to five years and weighing between 10 and 25 kg undergoing minor surgery requiring mask anaesthesia. In each case, after induction of anaesthesia, the LMA was inserted under direct vision to eliminate the possibility of epiglottic airway obstruction. The fresh gas flow was provided by a Jackson Rees modification of an Ayre's T-piece and was determined according to the following formula: 3 x (1000 + (100 x body weight)) LPM. Blood pressure, ECG, O2 saturation, temperature and end-tidal gas concentrations were recorded. The measures of peak PETCO2 were taken at pre-determined distances from the elbow connector down the LMA shaft. During the sampling sequence an arterial blood sample was taken for gas analysis. The PaCO2 was 63.5 +/- 9.3 mmHg (mean +/- SD). At any given sampling site, mean PETCO2 values were less than PaCO2 (P < 0.05). However, in eight patients PETCO2 values measured at the distal site were higher than the PaCO2 (negative P(a-ET)CO2 gradients).(ABSTRACT TRUNCATED AT 250 WORDS)


Circulating miR-221/222 expression as microRNA biomarker predicting tamoxifen treatment outcome: a case-control study.
The high mortality rate in breast cancer (BC) patients is generally due to metastases resistant to systemic therapy. Two causes of systemic therapy resistance in BC patients are circulating miRNAs-221 and miR-222, leading to improved BC cell proliferation, survival, and reduced cell apoptosis. This study investigated the miRNA expression changes associated with cancer cell resistance to tamoxifen therapy and is expected to be clinically meaningful before providing endocrine therapy to luminal-type BC patients who express them. This case-control research included individuals with the luminal subtype of BC who had received tamoxifen medication for around one year. Furthermore, the case group contained 15 individuals with local recurrence or metastases, while the control group comprised 19 patients without local recurrence or metastases. Plasma miR-221/222 quantification was performed with real-time PCR using transcript-specific primers. A significant difference was found in circulating miR-221 expression between cases and controls (P=0.005) but not in miR-222 expression (P=0.070). There were no significant differences between miR-221/222 expression, progesterone receptor, Ki67 protein levels, lymphovascular invasion, and stage. However, receiver operator characteristic curve analyses showed miR-221/222 expressions predictive of tamoxifen resistance (P=0.030) with a sensitivity of 60.00 and a specificity of 83.33%. The use of circulating miR-221/222 expression can predict relapse as well as resistance to tamoxifen treatment in BC patients, and their testing is recommended for luminal subtype BC patients who will undergo tamoxifen therapy to determine their risk of tamoxifen resistance early, increasing treatment effectiveness.


Dichotomizing sensory nerve fibers innervating both the lumbar vertebral body and the area surrounding the iliac crest: a possible mechanism of referred lateral back pain from lumbar vertebral body.
Animal study. To determine the existence of dichotomizing sensory nerve fibers innervating both the lumbar vertebral body and the area surrounding the iliac crest (ASIC). Elderly patients with osteoporosis sometimes experience lumbar vertebral fracture and may feel diffuse nonlocalized pain in the back, the lateral portion of the trunk, and the ASIC. The pattern of sensory innervation of vertebral bodies remains unclear. DRG neurons with dichotomizing axons have been reported and are thought to be related to referred pain. The purpose of this study was to investigate the existence of dichotomizing axons to the lumbar vertebral bodies and the ASIC in rats. Two kinds of neurotracers (1,1´-dioctadecyl-3,3,3´,3´-tetramethylindocarbocyanine perchlorate [DiI] and Fluoro-Gold [FG]) were used. DiI crystals were placed in the left ASIC, and FG was applied into the L2 vertebral body in 10 rats. Four weeks later, left DRGs from L1 to L6 were resected, sectioned, and observed under a fluorescence microscope. DiI-labeled DRG neurons innervating the ASIC and FG-labeled DRG neurons innervating the vertebral L2 body were distributed from L1 to L6. The ratio of total double-labeled per total DiI-labeled DRG neurons was 10.2%, and that of total double-labeled per total FG-labeled DRG neurons was 14.7%. These double-labeled DRG neurons innervating the L2 vertebral body had other axons that extended to the ASIC. This finding provides a possible neuroanatomical explanation for referred pain in the ASIC from vertebral bodies.


[Mucous membrane pemphigoid with ocular involvement. Part I: Clinical manifestations, pathogenesis and diagnosis].
Mucous membrane pemphigoid is a subepidermal blistering autoimmune disorder characterized by predominant involvement of mucous membranes and the presence of autoantibodies against proteins of the dermal-epidermal junction. Lesions most frequently develop in the oral cavity followed, in descending order of frequency, by conjunctiva, nasopharynx, the anogenital region, skin, larynx, and oesophagus. When the lesions are restricted to the conjunctiva, the term ocular pemphigoid may be applied. Cicatrization of the plica is considered a pathognomonic sign in early disease. Recurrent conjunctival inflammation results in subepithelial fibrosis, which leads to fornix shortening, symblepharon formation and subsequent trichiasis and entropion. Even in the absence of conjunctival inflammation, ankyloblepharon may occur. In end stage disease, limbal stem cell deficiency, tear deficiency, and lid malpositions may occur and result in a total keratinization of the ocular surface. The diagnosis is based on clinical findings and the detection of linear deposits of IgG and/or IgA and/or C3 at the dermal-epidermal junction by direct immunofluorescence microscopy of a perilesional biopsy. Autoantibodies (against type XVII and VII collagen, laminin 5 and 6, alpha6beta4 integrin, BP230) have been detected in patient serum. In the case of ocular involvement, preferential reactivity against beta4 integrin has been described.


A national survey of clubs medical personnel, facilities and protocols in Irish Rugby Union.
Rugby Union is one of the most popular sports in Ireland. Participation in all sports carries risk, and there is an onus on governing bodies and those involved in sport to minimise this risk using injury prevention and management programmes. The aim of this study was to evaluate the current status of medical personnel, facilities and equipment in Rugby Union clubs in Ireland. A nationwide cross sectional survey of affiliated clubs in Ireland was undertaken at the beginning of the 2011-2012. Clubs were surveyed on a range of variables including their medical personnel, facilities, equipment, policies and concussion. 47.7 % of those surveyed responded. The majority reported involvement of appropriate medically qualified personnel, having a dedicated medical area/room, a first aid kit and defibrillator, and a demand for first aid courses. This survey provided key information on the current medical status of clubs in Ireland to the governing body. Many clubs have adequate medical resources in place, however a large number do not have medical professionals working with them or own basic medical equipment. The results of this study have lead to the development and implementation of a rugby specific injury prevention and management programme for medical and non-medical personnel at all levels of the game in Ireland.


Profile of cadaveric liver donors of the OPO-UNICAMP From 2002 to 2006.
Four decades after the first successful liver transplantation, the organ donation shortage challenges the scientific community to create various new strategies. We sought to analyze the profile of registered cadaveric liver donors for an Organ Procurement Organization (OPO) during the period of 2002 through 2006. This retrospective analysis of 122 deceased donors in the OPO-Unicamp corresponded to the period of 2002 through 2006. Men were identified as 57.14% of donors and the overall average age was 32.88 years with 16.53% over 50 years of age. Analyzing the causes of brain death, cerebral trauma (CET) was responsible for 46.22% and cerebral vascular accidents, 33.61%. The percentage of use of vasoactive drugs was 88.43%. Observing the donors' backgrounds, we observed that 11.90% had alcoholism, 1.23% drug addiction and 27.78% infection. We verified cardiac arrest in 9.43%. In accordance with the expanded criteria of donation, 89.26% of donors fulfilled some of the criteria: 73.55%, one criterion; 14.05%, two; 1.65%, three; and no donor fulfilled 4 or 5. The donor profile in our unit is a young man with CET and who fulfills at least one expanded donation criterion. Finally, to increase the number of donors, the use of vasoactive drugs (89.26%), cardiopulmonary resuscitation (9.43%), and infection (27.78%) were not considered reasons to discard the liver.


Ballooned hepatocytes in steatohepatitis: the value of keratin immunohistochemistry for diagnosis.
Hepatocyte "ballooning" is an often used but ill defined term in liver pathology to designate a special form of liver cell degeneration associated with cell swelling and enlargement found particularly in steatohepatitis. Alterations of the intermediate filament cytoskeleton of the hepatocyte may contribute to the pathogenesis of this microscopic change. Ballooning degeneration is considered a hallmark of steatohepatitis, but enlarged hepatocytes may also be observed in a variety of other acute and chronic liver diseases. The intermediate filament cytoskeleton was investigated using keratin 8 and 18 immunohistochemistry in liver diseases associated with enlarged or ballooned hepatocytes. Keratin 8/18 immunostaining was drastically reduced or lost in the cytoplasm of ballooned hepatocytes in alcoholic and non-alcoholic steatohepatitis, chronic cholestatic conditions, ischemia/reperfusion injury and in ballooned hepatocytes in chronic hepatitis C cases with concurrent steatohepatitis. In contrast, substantial decrease or loss of keratin 8/18 immunostaining was not noted in cases of acute hepatitis, giant cell hepatitis, chronic hepatitis B, or autoimmune hepatitis. Loss of keratin 8/18 immunostaining can serve as an objective marker of a specific type of ballooning degeneration of hepatocytes. Oxidative stress may be a common denominator in the pathogenesis of keratin filament alterations in these conditions.


Relationship between duration of unilateral masticatory cycles and the type of lateral dental guidance: a preliminary study.
This study assessed the duration of different phases of the chewing cycle and the height of the masticatory cycle in relation to the type of lateral guidance. Fifty-three subjects with the same type of lateral guidance on both sides were categorized into 3 groups: anterior protected articulation, canine protection, and group function. Overbite was measured clinically. Border jaw movements were recorded using a Sirognathograph, and the lateral guidance angle in the frontal plane was measured. Jaw movements during unilateral chewing of peanuts were recorded on the frontal plane using the Sirognathograph connected to an electrocardiograph used for transcription. A single masticatory cycle was divided into opening, closing, and occlusal-level phases. Masticatory parameters were analyzed by one-way analysis of variance, correlations, the paired Student t test, and multiple linear regression. Women showed significantly longer total cycle duration than men. Subjects with canine protection showed the highest lateral guidance angle and the highest chewing cycle duration. Subjects with anterior protected articulation exhibited significantly longer occlusal-level phases. Fifty-nine percent of the variation in duration of the occlusal-level phase can be explained by the type of lateral dental guidance, gender, and lateral guidance angle. Only overbite was a predictor of height of mastication. The type of lateral guidance, gender, and frontal guidance angle are correlated with the duration of the occlusal-level phase during unilateral chewing of peanuts. The height of mastication cannot be explained by the type of lateral guidance.


Mining the Proteome of Toxoplasma Parasites Seeking Vaccine and Diagnostic Candidates.
Toxoplasma gondii is a pathogenic protozoan parasite that infects the nucleated cells of warm-blooded hosts leading to an infectious zoonotic disease known as toxoplasmosis. The infection outcomes might be severe and fatal in patients with immunodeficiency, diabetes, and pregnant women and infants. The One Health approach to toxoplasmosis highlights that the health of humans is closely related to the health of animals and our common environment. The presence of drug resistance and side effects, the further improvement of sensitivity and specificity of serodiagnostic tools and the potentiality of vaccine candidates to induce the host immune response are considered as justifiable reasons for the identification of novel targets for the better management of toxoplasmosis. Thus, the identification of new critical proteins in the proteome of Toxoplasma parasites can also be helpful in designing and test more effective drugs, vaccines, and diagnostic tools. Accordingly, in this study we present important proteins found in the proteome of the life cycle-specific stages of Toxoplasma parasites that are potential diagnostic or vaccine candidates. The current study might help to understand the complexity of these parasites and provide a possible source of strategies and biomolecules that can be further evaluated in the pathobiology of Toxoplasma parasites and for diagnostics and vaccine trials against this disease.


Visible 532 nm laser irradiation of human adipose tissue-derived stem cells: effect on proliferation rates, mitochondria membrane potential and autofluorescence.
The photobiological effect of laser light on cells and tissues originates from light absorption by endogenous chromophores and hence it depends on the wavelength of light source and cell type. Earlier studies regarding the biostimulation effects of green laser light investigated a wide variety of cells but not adipose tissue-derived stem cells (ADSCS). In this study we reported the in vitro effect of 532-nm Nd:YAG laser on proliferation, mitochondrial activity of these mesenchymal stem cells (MSCs) on the autofluorescence emission at wavelengths associated with nicotinamide adenine dinucleotide (NADH) and flavoproteins. ADSCS were exposed to 532 nm second harmonic generation laser light at moderate power density (0.153 W/cm(2)) for periods of 30, 45, 60, 180, and 300 seconds. Mitochondrial membrane potential was measured using JC1 stain and confocal laser scanning microscopy, cell proliferation rates, and cellular autofluorescence emission at 450 and 540 nm wavelengths were measured using micro plate spectrofluorometer 48 hours after irradiation. Shorter (30-60 seconds) exposure times led to significantly increased proliferation, attributed to increased mitochondrial activity (P < 0.05). At longer exposures we observed a significant decrease in proliferation and autofluorescence (P < 0.05). Strong correlation was observed between proliferation rates of cells and autofluorescence intensity. Our results show that autofluorescence of the respiratory chain components and key autofluorescent metabolites offers a non-invasive method to quantify cellular response to laser irradiation.


Family Screening in Dilated Cardiomyopathy: Prevalence, Incidence, and Potential for Limiting Follow-Up.
According to patterns of inheritance and incomplete penetrance, fewer than half of relatives to dilated cardiomyopathy probands will develop disease. The purpose of this study was to investigate the prevalence and incidence, and to identify predictors of developing familial dilated cardiomyopathy (FDC) in relatives participating in family screening. The study was a retrospective, longitudinal cohort study of families screened and followed from 2006 to 2020 at a regional assembly of clinics for inherited cardiomyopathies. In total, 211 families (563 relatives, 50% women) were included. At baseline, 124 relatives (22%) were diagnosed with FDC. Genetic sequencing identified the etiology in 37% of screened families and classified 101 (18%) relatives as unaffected carriers (n = 43) or noncarriers (ie, not at risk of FDC [n = 58]). The combined clinical and genetic baseline yield was 30%. During follow-up (2,313 person-years, median 5.0 years), 45 developed FDC (incidence rate of 2.0% per person-year; 95% CI: 1.4%-2.8%), increasing the overall yield to 34%. The incidence rate of FDC was high in relatives with baseline abnormalities on electrocardiogram or echocardiography compared with relatives with normal findings (4.7% vs 0.4% per person-year; HR: 12.9; P < 0.001). In total, baseline screening identified 326 (58%) relatives to be at low risk of FDC. Family screening identified a genetic predisposition to or overt FDC in 1 of 3 relatives at baseline. Genetic and clinical screening was normal in more than half of relatives, and these relatives had a low risk of developing FDC during follow-up. Thus, baseline screening identified a large proportion, in whom follow-up may safely be reduced, allowing focused follow-up of relatives at risk.


Aggregatibacter actinomycetemcomitans adhesion inhibited in a flow cell.
Microbial interactions are considered important in the adhesion process of pathogenic bacteria in the oral cavity. This study addressed the hypothesis that a streptococcal biofilm influences the hard tissue colonization by the periodontopathogen Aggregatibacter actinomycetemcomitans under hydrodynamic conditions. The colonization of a green-fluorescent-protein-labelled A. actinomycetemcomitans strain on surfaces coated with a streptococcal biofilm, was monitored in real time using a confocal laser scanning microscope-mounted flow cell. Culture and quantitative polymerase chain reaction data were obtained in parallel from a Modified Robbins Device. Colonization of A. actinomycetemcomitans was inhibited by the four tested streptococci (Streptococcus sanguinis, Streptococcus cristatus, Streptococcus salivarius, and Streptococcus mitis). The most inhibiting species was S. sanguinis. These results confirmed the hypothesis that some bacterial species influence A. actinomycetemcomitans colonization of hard surfaces in vitro under hydrodynamic conditions.


CoDP: predicting the impact of unclassified genetic variants in MSH6 by the combination of different properties of the protein.
Lynch syndrome is a hereditary cancer predisposition syndrome caused by a mutation in one of the DNA mismatch repair (MMR) genes. About 24% of the mutations identified in Lynch syndrome are missense substitutions and the frequency of missense variants in MSH6 is the highest amongst these MMR genes. Because of this high frequency, the genetic testing was not effectively used in MSH6 so far. We, therefore, developed CoDP (Combination of the Different Properties), a bioinformatics tool to predict the impact of missense variants in MSH6. We integrated the prediction results of three methods, namely MAPP, PolyPhen-2 and SIFT. Two other structural properties, namely solvent accessibility and the change in the number of heavy atoms of amino acids in the MSH6 protein, were further combined explicitly. MSH6 germline missense variants classified by their associated clinical and molecular data were used to fit the parameters for the logistic regression model and to assess the prediction. The performance of CoDP was compared with those of other conventional tools, namely MAPP, SIFT, PolyPhen-2 and PON-MMR. A total of 294 germline missense variants were collected from the variant databases and literature. Of them, 34 variants were available for the parameter training and the prediction performance test. We integrated the prediction results of MAPP, PolyPhen-2 and SIFT, and two other structural properties, namely solvent accessibility and the change in the number of heavy atoms of amino acids in the MSH6 protein, were further combined explicitly. Variants data classified by their associated clinical and molecular data were used to fit the parameters for the logistic regression model and to assess the prediction. The values of the positive predictive value (PPV), the negative predictive value (NPV), sensitivity, specificity and accuracy of the tools were compared on the whole data set. PPV of CoDP was 93.3% (14/15), NPV was 94.7% (18/19), specificity was 94.7% (18/19), sensitivity was 93.3% (14/15) and accuracy was 94.1% (32/34). Area under the curve of CoDP was 0.954, that of MAPP for MSH6 was 0.919, of SIFT was 0.864 and of PolyPhen-2 HumVar was 0.819. The power to distinguish between pathogenic and non-pathogenic variants of these methods was tested by Wilcoxon rank sum test (p < 8.9 × 10(-6) for CoDP, p < 3.3 × 10(-5) for MAPP, p < 3.1 × 10(-4) for SIFT and p < 1.2 × 10(-3) for PolyPhen-2 HumVar), and CoDP was shown to outperform other conventional methods. In this paper, we provide a human curated data set for MSH6 missense variants, and CoDP, the prediction tool, which achieved better accuracy for predicting the impact of missense variants in MSH6 than any other known tools. CoDP is available at http://cib.cf.ocha.ac.jp/CoDP/.


Mesophyll conductance to CO2 in leaves of Siebold's beech (Fagus crenata) seedlings under elevated ozone.
Ozone is an air pollutant that negatively affects photosynthesis in woody plants. Previous studies suggested that ozone-induced reduction in photosynthetic rates is mainly attributable to a decrease of maximum carboxylation rate (Vcmax) and/or maximum electron transport rate (Jmax) estimated from response of net photosynthetic rate (A) to intercellular CO2 concentration (Ci) (A/Ci curve) assuming that mesophyll conductance for CO2 diffusion (gm) is infinite. Although it is known that Ci-based Vcmax and Jmax are potentially influenced by gm, its contribution to ozone responses in Ci-based Vcmax and Jmax is still unclear. In the present study, therefore, we analysed photosynthetic processes including gm in leaves of Siebold's beech (Fagus crenata) seedlings grown under three levels of ozone (charcoal-filtered air or ozone at 1.0- or 1.5-times ambient concentration) for two growing seasons in 2016-2017. Leaf gas exchange and chlorophyll fluorescence were simultaneously measured in July and September of the second growing season. We determined the A, stomatal conductance to water vapor and gm, and analysed A/Ci curve and A/Cc curve (Cc: chloroplast CO2 concentration). We also determined the Rubisco and chlorophyll contents in leaves. In September, ozone significantly decreased Ci-based Vcmax. At the same time, ozone decreased gm, whereas there was no significant effect of ozone on Cc-based Vcmax or the contents of Rubisco and chlorophyll in leaves. These results suggest that ozone-induced reduction in Ci-based Vcmax is a result of the decrease in gm rather than in carboxylation capacity. The decrease in gm by elevated ozone was offset by an increase in Ci, and Cc did not differ depending on ozone treatment. Since Cc-based Vcmax was also similar, A was not changed by elevated ozone. We conclude that gm is an important factor for reduction in Ci-based Vcmax of Siebold's beech under elevated ozone.


Expression and characterization of hydroxyindole O-methyltransferase from a cloned cDNA in Chinese hamster ovary cells.
We have used two kinds of expression systems to test whether the cloned cDNA encoding hydroxyindole O-methyltransferase (HIOMT) of the bovine pineal gland was functional or not. First, when mRNA was synthesized in vitro by the SP6 system and injected into Xenopus oocytes, the enzymatic activity was expressed in the oocytes. Second, the cloned cDNA was recombined to a vector under the control of the simian virus 40 early promoter and transfected to Chinese hamster ovary (CHO) cells. The enzymatic activity of the crude supernatant of transfected cells (CHO-HT2) reached to 400 pmol melatonin formed per min per mg of protein, which value was approximately 9% of that of bovine pineal supernatant. The amounts of enzyme protein estimated by immunoblotting were proportional to the enzymatic activity in both CHO and pineal gland. The content of HIOMT protein was 8- to 30-fold larger in pineal gland compared to CHO cells. On the other hand, the content of mRNA encoding the enzyme measured by dot hybridization with [32P]cDNA, was in the same range in both CHO cells and pineal glands. These data suggest that the 11-fold higher enzymatic activity in pineal gland is due to an accumulation of the enzyme protein, not to a high level of the mRNA and also indicate that the cloned cDNA can express an intact hydroxyindole O-methyltransferase enzyme in CHO cells.


Early clinical and radiological outcomes of the new porous titanium shell in combination with locking screw in revision total hip arthroplasty.
Extensive acetabular bone loss and poor bone quality are two key challenges often encountered in revision total hip arthroplasty. A new 3D-printed porous acetabular shell has been made available with the option to insert multiple variable-angle locking screws. We sought to evaluate the early clinical and radiological outcomes of this construct. A retrospective review of patients operated by two surgeons was performed in a single institution. Fifty-nine revision hip arthroplasties were performed in 55 patients (34 female; mean age 68.8 ± 12.3 years) for Paprosky defects I (n = 21), IIA/B (n = 22), IIC (n = 9), III (n = 7) between February 2018 and January 2022 using the novel porous titanium acetabular shell and multiple variable angle locking screws. Postoperative clinical and radiographic outcomes were locally maintained. Patient-reported outcome measures collected included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Oxford Hip Score, and the 12-item Short Form Survey. After a mean follow-up of 25.7 ± 13.9 months, two cases of shell migration were noted. One patient had a failed constrained mechanism and received revision to a cemented dual mobility liner. No other acetabular shells showed any evidence of radiographic loosening at the final follow-up. Preoperatively, 21 defects were classified as Paprosky grade I, 19 grade IIA, 3 grade IIB, 9 IIC, 4 grade IIIA, and 3 IIIB. The mean postoperative WOMAC function score was 84 (SD 17), WOMAC (stiffness) 83 (SD 15), WOMAC (pain) 85 (SD 15), and WOMAC (global) 85 (SD 17). The mean postoperative OHS was 83 (SD 15), and mean SF-12 physical score was 44 (SD 11). The additional augmentation of porous metal acetabular shells with multiple variable-angle locking screws provides reliable initial fixation with good clinical and radiological outcomes in the short term. Further studies are needed to establish the medium- and long-term outcomes. IV.


In ACS, prasugrel reduces 30-day MACE and mortality vs. ticagrelor or clopidogrel; no differences for major bleeding.
Baldetti L, Melillo F, Moroni F, et al. Meta-analysis comparing P2Y12 inhibitors in acute coronary syndrome. Am J Cardiol. 2020;125;1815-22. 32305225.


Retrobulbar lipofilling to correct the enophthalmos.
In this article, we describe an alternative procedure to restore the retrobulbar volume in enophthalmic patients. We report the case of a patient with a late enophthalmos we submitted to retrobulbar lipofilling to correct the defect. The preoperative assessment and the surgical technique are described in detail. The volume of fat injected was 3.2 mL, with a satisfying increase in exophthalmometry measurements. The procedure was well tolerated without complications. Retrobulbar lipofilling for enophthalmos appears to be a safe alternative technique for orbital volume enhancement. It avoids the use of alloplastic materials and allows to obtain good cosmetic results with an easy technique and minimal donor-site morbidity.


Depletion of the upper mantle by convergent tectonics in the Early Earth.
Partial melting of mantle peridotites at spreading ridges is a continuous global process that forms the oceanic crust and refractory, positively buoyant residues (melt-depleted mantle peridotites). In the modern Earth, these rocks enter subduction zones as part of the oceanic lithosphere. However, in the early Earth, the melt-depleted peridotites were 2-3 times more voluminous and their role in controlling subduction regimes and the composition of the upper mantle remains poorly constrained. Here, we investigate styles of lithospheric tectonics, and related dynamics of the depleted mantle, using 2-D geodynamic models of converging oceanic plates over the range of mantle potential temperatures (Tp = 1300-1550 °C, ∆T = T - Tmodern = 0-250 °C) from the Archean to the present. Numerical modeling using prescribed plate convergence rates reveals that oceanic subduction can operate over this whole range of temperatures but changes from a two-sided regime at ∆T = 250 °C to one-sided at lower mantle temperatures. Two-sided subduction creates V-shaped accretionary terrains up to 180 km thick, composed mainly of highly hydrated metabasic rocks of the subducted oceanic crust, decoupled from the mantle. Partial melting of the metabasic rocks and related formation of sodic granitoids (Tonalite-Trondhjemite-Granodiorite suites, TTGs) does not occur until subduction ceases. In contrast, one sided-subduction leads to volcanic arcs with or without back-arc basins. Both subduction regimes produce over-thickened depleted upper mantle that cannot subduct and thus delaminates from the slab and accumulates under the oceanic lithosphere. The higher the mantle temperature, the larger the volume of depleted peridotites stored in the upper mantle. Extrapolation of the modeling results reveals that oceanic plate convergence at ∆T = 200-250 °C might create depleted peridotites (melt extraction of > 20%) constituting more than half of the upper mantle over relatively short geological times (~ 100-200 million years). This contrasts with the modeling results at modern mantle temperatures, where the amount of depleted peridotites in the upper mantle does not increase significantly with time. We therefore suggest that the bulk chemical composition of upper mantle in the Archean was much more depleted than the present mantle, which is consistent with the composition of the most ancient lithospheric mantle preserved in cratonic keels.


Characterization of vaginal Lactobacillus species by rplK -based multiplex qPCR in Russian women.
We describe a multiplex qPCR assay for identification and quantitative assessment of a set of vaginal Lactobacillus species, including L. acidophilus, L. crispatus, L. gasseri, L. helveticus, L. iners, and L. jensenii. The assay extends the previously developed qPCR method for Lactobacillus detection and total quantification based on targeting the rplK gene. Both assays use only single pair of primers and a set of probes combined in three reactions, comprising a vaginal Lactobacillus diagnostic assay panel. The utility of the diagnostic panel was evaluated by analyzing of vaginal swab specimens from 145 patients with different status of vaginal health. Most frequently, only one Lactobacillus species was dominant (68,9%), mostly L. crispatus (18,6%) or L. iners (33,1%), but two or three Lactobacillus species were also being simultaneously detected (24,9%). The diagnostic panel will facilitate investigations of the role of Lactobacillus species in the health of the female reproductive system and promote studies of variability of the vaginal microbiota.


Structural Considerations in Affinity Maturation of Antibody-Based Biotherapeutic Candidates.
Affinity maturation is an important stage in biologic drug discovery as is the natural process of generating an immune response inside the human body. In this chapter, we describe in silico approaches to affinity maturation via a worked example. Both advantages and limitations of the computational methods used are critically examined. Furthermore, construction of affinity maturation libraries and how their outputs might be implemented in an experimental setting are also described. It should be noted that structure-based design of biologic drugs is an emerging field and the tools currently available require further development. Furthermore, there are no standardized structure-based strategies yet for antibody affinity maturation as this research relies heavily on scientific logic as well as creative intuition.


Prolyl isomerase Pin1 in metabolic reprogramming of cancer cells.
Pin1 is one member of a group consisting of three prolyl isomerases. Pin1 interacts with the motif containing phospho-Ser/Thr-Pro of substrates and enhances cis-trans isomerization of peptide bonds, thereby controlling the functions of these substrates. Importantly, the Pin1 expression level is highly upregulated in most cancer cells and correlates with malignant properties, and thereby with poor outcomes. In addition, Pin1 was revealed to promote the functions of multiple oncogenes and to abrogate tumor suppressors. Accordingly, Pin1 is well recognized as a master regulator of malignant processes. Recent studies have shown that Pin1 also binds to a variety of metabolic regulators, such as AMP-activated protein kinase, acetyl CoA carboxylase and pyruvate kinase2, indicating Pin1 to have major impacts on lipid and glucose metabolism in cancer cells. In this review, we focus on the roles of Pin1 in metabolic reprogramming, such as "Warburg effects", of cancer cells. Our aim is to introduce these important roles of Pin1, as well as to present evidence supporting the possibility of Pin1 inhibition as a novel anti-cancer strategy.


ICV testosterone induces Fos in male Syrian hamster brain.
Previous studies in our laboratory have demonstrated intracerebroventricular (ICV) self-administration of testosterone in hamsters. This suggests that androgens are reinforcing, independent of their anabolic effects. Furthermore, pharmacologic testosterone acts as a depressant: ICV testosterone infusion acutely reduces respiration, locomotion and body temperature. However, with chronic exposure, males develop tolerance. To understand mechanisms for androgen action, we looked for Fos expression after acute and chronic ICV infusion of testosterone or vehicle. 32 castrated males with chronic physiologic testosterone replacement (n=8/group) were infused ICV for 4h/day with 40 microg testosterone or 40 microl vehicle. Half of the males were perfused after the first day of ICV infusion; the remaining males were perfused after 15 days of ICV infusion. 60 microm coronal brain slices were cut. Every fourth section was stained for Fos. Additional sections were stained for androgen receptors (AR) and estrogen receptors (ER). Testosterone infusion induced Fos above control in the posteromedial bed nucleus of the stria terminalis (BSTPM), posteromedial amygdala (MeP), lateral habenula (LHb), median raphe (MnR), lateral pontine nucleus (Pn), and ventral tegmental area (VTA). In particular, Fos was elevated in the BSTPM, MeP, LHb, and VTA only after 1 day of testosterone. 15 days of testosterone enhanced Fos expression above control in the MnR and lateral Pn. Importantly, Fos was not present in all brain areas involved in reward or in those with dense steroid receptors. Furthermore, AR and ER immunostaining was unaltered by testosterone infusion. We conclude that pharmacologic testosterone activates select steroid-sensitive brain regions, as well as midbrain areas involved in reinforcement of commonly-abused drugs.


Telemedicine in Neuro-Oncology-An Evaluation of Remote Consultations during the COVID-19 Pandemic.
In order to minimize the risk of infections during the COVID-19 pandemic, remote video consultations (VC) experienced an upswing in most medical fields. However, telemedicine in neuro-oncology comprises unique challenges and opportunities. So far, evidence-based insights to evaluate and potentially customize current concepts are scarce. To fill this gap, we analyzed >3700 neuro-oncological consultations, of which >300 were conducted as VC per patients' preference, in order to detect how both patient collectives distinguished from one another. Additionally, we examined patients' reasons, suitable/less suitable encounters, VC's benefits and disadvantages and future opportunities with an anonymized survey. Patients that participated in VC had a worse clinical condition, higher grade of malignancy, were more often diagnosed with glioblastoma and had a longer travel distance (all p < 0.01). VC were considered a fully adequate alternative to face-to-face consultations for almost all encounters that patients chose to participate in (>70%) except initial consultations. Most participants preferred to alternate between both modalities rather than participate in one alone but preferred VC over telephone consultation. VC made patients feel safer, and participants expressed interest in implementing other telemedicine modalities (e.g., apps) into neuro-oncology. VC are a promising addition to patient care in neuro-oncology. However, patients and encounters should be selected individually.


2-(3-Methyl-2-oxoquinoxalin-1-yl)-N-(4-methyl-phen-yl)acetamide.
The quinoxaline moiety in the title mol-ecule, C18H17N3O2, is not quite planar and the p-tolyl group is rotationally disordered over two nearly equally populated sets of sites. In the crystal, N-H⋯O and C-H⋯O hydro-gen bonds form chains extending along the b-axis direction. Due to the disorder of the p-tolyl rings, short C⋯C distances are observed between adjacent chains.


Association between IGF-IR, m-calpain and UCP-3 gene polymorphisms and growth traits in Nanyang cattle.
The objective of this study was to estimate the allele and genotype frequencies of the IGF-IR/TaqI, m-calpain/HhaI, and UCP-3/BglI polymorphisms and to determine associations between these polymorphisms and growth traits in Chinese indigenous cattle breeds. Genotyping was performed on 321 animals including 135 Nanyang, 80 Qinchuan, and 106 Jiaxian cattle. No significant differences in growth traits were observed between the genotypes of IGF-IR/TaqI polymorphism in Nanyang cattle. The m-calpain/HhaI, and UCP-3/BglI polymorphisms were associated with body weight, withers height, and body length of 6 months (P < 0.05 or P < 0.01), body length of 18 months (P < 0.05), and body length and heart girth of 24 months (P < 0.01) in Nanyang cattle. In addition, Nanyang cattle aged 12 months with AB genotype of m-calpain/HhaI polymorphism had higher body length and heart girth than those with BB genotype (P < 0.01). The withers height were greater (P < 0.01) in Nanyang cattle aged 12 months with genotype AB of UCP-3/BglI polymorphism than those with genotype BB. The Nanyang cattle aged 24 months with genotype AA had higher withers height than those with genotype BB (P < 0.05). In conclusion, the m-calpain/HhaI and UCP-3/BglI polymorphisms may be used as DNA markers for selection in the breeding process of Nanyang cattle.


Abiraterone acetate versus docetaxel for metastatic castration-resistant prostate cancer: a cohort study within the French nationwide claims database.
To conduct the direct comparison of abiraterone acetate and docetaxel for first-line treatment of metastatic castration-resistant prostate cancer (mCRPC) in real-life settings. Data were extracted from the French nationwide claims database (SNDS) on all men aged ≥40 years starting first-line treatment with abiraterone acetate or docetaxel for mCRPC in 2014. A high-dimensional propensity score including 100 baseline characteristics was used to match patients of both groups and form two comparative cohorts. Three-year overall survival and treatment discontinuation-free survival were determined using Kaplan-Meier analysis. In 2014, 2,444 patients started abiraterone for treatment of mCRPC and 1,214 started docetaxel. After trimming and matching, 716 patients were available in each group. Median overall survival tended to be longer in the abiraterone acetate cohort (23.8 months, 95% confidence interval = [21.5; 26.0]) than in the docetaxel cohort (20.3 [18.4; 21.6] months). Survival at 36 months was 34.6% for abiraterone acetate and 27.9% for docetaxel (p = 0.0027). Treatment discontinuation-free median was longer in the abiraterone acetate cohort compared to the docetaxel cohort (10.8 [10.1; 11.7] versus 7.4 [7.0; 8.0] months). The findings underline the interest of oral abiraterone acetate over intravenous docetaxel as the first-line treatment option in mCRPC.


A Maximum-Entropy approach for accurate document annotation in the biomedical domain.
The increasing number of scientific literature on the Web and the absence of efficient tools used for classifying and searching the documents are the two most important factors that influence the speed of the search and the quality of the results. Previous studies have shown that the usage of ontologies makes it possible to process document and query information at the semantic level, which greatly improves the search for the relevant information and makes one step further towards the Semantic Web. A fundamental step in these approaches is the annotation of documents with ontology concepts, which can also be seen as a classification task. In this paper we address this issue for the biomedical domain and present a new automated and robust method, based on a Maximum Entropy approach, for annotating biomedical literature documents with terms from the Medical Subject Headings (MeSH).The experimental evaluation shows that the suggested Maximum Entropy approach for annotating biomedical documents with MeSH terms is highly accurate, robust to the ambiguity of terms, and can provide very good performance even when a very small number of training documents is used. More precisely, we show that the proposed algorithm obtained an average F-measure of 92.4% (precision 99.41%, recall 86.77%) for the full range of the explored terms (4,078 MeSH terms), and that the algorithm's performance is resilient to terms' ambiguity, achieving an average F-measure of 92.42% (precision 99.32%, recall 86.87%) in the explored MeSH terms which were found to be ambiguous according to the Unified Medical Language System (UMLS) thesaurus. Finally, we compared the results of the suggested methodology with a Naive Bayes and a Decision Trees classification approach, and we show that the Maximum Entropy based approach performed with higher F-Measure in both ambiguous and monosemous MeSH terms.


Enhancement of working memory performance in the rat by MDL 26,479, a novel compound with activity at the GABAA receptor complex.
MDL 26,479, a novel triazole compound with action at the GABAA receptor complex, was examined in 2 models of working memory deficit in the rat. MDL 26,479 attenuated a scopolamine-induced acquisition deficit in a T-maze reinforced alternation task. MDL 26,479 also reversed a performance deficit induced by increased delay between sample and choice trials in the same task, suggesting that the compound may have memory enhancing potential. This finding further supports claims that drugs acting at the GABAA receptor complex are of potential use in the treatment of memory disorder.


Biomechanical factors in abdominal aortic aneurysm rupture.
Hitherto the size of abdominal aortic aneurysms (AAA) has been considered the most important factor in determining the risk of rupture. For this reason most interest has been devoted to physical, echographic and tomographic analyses of the shape of AAA. However, it is known that rupture can also occur in small AAA. Other factors must be considered to have an important role in the natural history of aneurysms. The aim of this study was to characterise the mechanical stress in the wall of an AAA due to pressure in the presence of atherosclerosis, intraluminal thrombus and anatomical restraints. The Finite Elements Method (FEM) was used to determine wall stress distribution. Due to the simplicity of the AAA structure an axisymmetric model has been built. The results of the structural analysis confirms that maximum stress increases with diameter. These effects may be reduced by the presence of intraluminal thrombus, which in the models reduces maximum stress by up to 30%; however this is not the case for dissecting thrombus. On the other hand atherosclerotic plaques cause stress concentration and a significant increase in maximum wall stress. The risk of rupture can increase by about 200%. Finally the investigation shows the FEM is a versatile tool for studying the mechanics of vascular structures. It enables the influence of various parameters on wall stress to be quantified in diagnostic settings, and so could be useful for predicting the rupture of AAA, although at present such predictions are limited by data leakage and by the approximations used in the model.


Diving Deep into Deep Learning: An Update on Artificial Intelligence in Retina.
In the present article, we will provide an understanding and review of artificial intelligence in the subspecialty of retina and its potential applications within the specialty. Given the significant use of diagnostic imaging within retina, this subspecialty is a fitting area for the incorporation of artificial intelligence. Researchers have aimed at creating models to assist in the diagnosis and management of retinal disease as well as in the prediction of disease course and treatment response. Most of this work thus far has focused on diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity, although other retinal diseases have started to be explored as well. Artificial intelligence is well-suited to transform the practice of ophthalmology. A basic understanding of the technology is important for its effective implementation and growth.


Subchronic metabolic effects and toxicity of a simulated pulp mill effluent on juvenile lake trout, Salmo trutta m. lacustris.
Juvenile lake trout (Salmo trutta m. lacustris) were exposed for 7 weeks to 0.05X and 0.2X 96-hr LC50 concentrations of simulated bleached kraft pulp mill effluent (KME - Sa + CP). A sulfate soap preparation, composed mainly of resin and fatty acids, with added chlorophenols (CP, tri-, tetra-, and penta-CP) was used as the toxicant mixture. Concentrations of free CP in plasma and free and conjugated CP in bile were proportional to their concentrations in the water. The greatest total gradient between bile and water CP was 5.2 X 10(4) for pentachlorophenol. The activity of a liver polysubstrate monooxygenase (PSMO) system, assayed with three model substrates, increased 40 to 67% due to KME - Sa + CP. However, the increase was not directly dependent on the exposure concentration. In contrast to PSMO, activities of conjugating enzymes (p-nitrophenol UDP-glucuronosyl and glutathione transferases) were decreased in the liver. Increased concentration of glutathione was noted in the liver and kidney. In addition, a small (9%) but significant decrease in blood hemoglobin concentration was observed at the higher exposure concentration. Although growth rate of lake trout was markedly decreased due to KME - Sa + CP, hydromineral balance and carbohydrate metabolism in fish were unaffected, indicating possible physiological compensation. On the other hand, lethality tests with lake trout preexposed to KME - Sa + CP at 0.2 X LC50 revealed decreased tolerance, whereas at the lower exposure concentration it was unchanged. We therefore conclude that various physiological adjustments in trout during subchronic exposures were not adaptive in terms of short-term tolerance.


Combining stimulus fading, reinforcement, and extinction to treat food refusal.
The food refusal of a 6-year-old girl with destructive behavior was treated using stimulus fading, reinforcement, and escape extinction. Intake increased and compliance with prompting procedures remained relatively stable despite the increased consumption requirement.


Genome-wide association study reveals useful QTL and genes controlling the fatty acid composition in rice bran oil using Vietnamese rice landraces.
In rice (Oryza sativa L.), rice bran contains valuable nutritional constituents, such as high unsaturated fat content, tocotrienols, inositol, γ-oryzanol, and phytosterols, all of which are of nutritional and pharmaceuticals interest. There is now a rising market demand for rice bran oil, which makes research into their content and fatty acid profile an area of interest. As it is evident that lipid content has a substantial impact on the eating, cooking, and storage quality of rice, an understanding of the genetic mechanisms that determine oil content in rice is of great importance, equal to that of rice quality. Therefore, in this study, we performed a genome-wide association study on the composition and oil concentration of 161 Vietnamese rice varieties. Five categories of fatty acids in rice bran were discovered and the bran oil concentration profile in different rice accessions was identified. We also identified 229 important markers related to the fatty acid composition of bran oil, distributed mainly on chromosomes 1 and 7. Seven quantitative trait loci and five potential genes related to unsaturated fatty acid content were detected, including OsKASI, OsFAD, OsARF, OsGAPDH, and OsMADS29. These results provide insights into the genetic basis of rice bran oil composition, which is pivotal to the metabolic engineering of rice plants with desirable bran oil content through candidate genes selection.


Can urodynamic studies be dispensed with in the initial urologic management of children with meningomyelocele? A study of 30 cases and review of the literature.
To identify whether a relationship exists between information gathered from voiding patterns, neurological status and radiological findings, and the actual dysfunction seen on cystometry in children with spina bifida. Thirty consecutive children with spina bifida underwent clinical evaluation, urinary tract imaging and cystometry. The clinical and radiological data were correlated with actual bladder dysfunction. Cystometry was abnormal in 87% with overactive detrusor in 77%. Seventeen patients (57%) had significant residual urine of whom all had neurological or voiding abnormalities. Irrespective of radiological findings (abnormal in 53%), 90% of these patients had detrusor overactivity and 10% an underactive detrusor. In the group with insignificant residual urine (n=13), upper tract was abnormal in six (46%) of which four had neurological/voiding abnormalities and detrusor overactivity. The other two patients with normal neurologic status and voiding pattern had normal cystometry, but their upper tract damage was inexplicable. Of the patients with insignificant residual urine and normal upper tracts (n=7), four had neurologic/voiding abnormalities, three with an overactive detrusor and one underactive detrusor, and of the other three, one had an overactive detrusor. Patients with significant residual urine can be presumed to have detrusor overactivity and may be initially managed with clean intermittent catheterization and bladder relaxants. Cystometry is indicated if upper tract shows deterioration. In patients with insignificant residual urine and abnormal clinical evaluation or radiology, detrusor overactivity can be presumed and urodynamic studies deferred. Patients with insignificant residual urine, normal radiology but abnormal clinical findings must undergo initial cystometry.


Special Section on Ethics in Health Informatics.
To summarize significant research contributions on ethics in medical informatics published in 2019. An extensive search using PubMed/Medline was conducted to identify the scientific contributions published in 2019 that address ethics issues in medical informatics. The selection process comprised three steps: 1) 15 candidate best papers were first selected by the two section editors; 2) external reviewers from internationally renowned research teams reviewed each candidate best paper; and 3) the final selection of three best papers was conducted by the editorial committee of the Yearbook. The three selected best papers explore timely issues of concern to the community and demonstrate how ethics considerations influence applied informatics. With regard to ethics in informatics, data sharing and privacy remain primary areas of concern. Ethics issues related to the development and implementation of artificial intelligence is an emerging topic of interest.


Is frozen section effective for diagnosis of unsuspected gallbladder cancer during laparoscopic cholecystectomy?
Although frozen section is recommended to prevent tumor dissemination following laparoscopic cholecystectomy (LC) for unsuspected gallbladder cancer, there are no reports concretely demonstrating its effectiveness and outcome. Frozen section during LC was performed in 990 patients with gallstones. The sensitivity, specificity of frozen section, and false-negative cases were evaluated in comparison with postoperative entire cross sections. In frozen section, 983 cases were diagnosed as benign and 7 cases as malignant. Of the benign cases, cancer was discovered in 4 patients postoperatively in which frozen section was diagnosed as regenerative epithelial severe atypia. Sensitivity was 64% and specificity was 100%. Concerning the results of frozen section by p-TNM classification, cancer was diagnosed in 40% of Tis lesions, whereas it was found in 83% of T2 or T3 lesions. Frozen section is effective in cases with T2 or greater lesions for which conversion to radical surgery should be required.


Unique features of secretory granules observed in the pituitary growth hormone-secreting (GH) cells of the musk shrew (Suncus murinus L).
Unique rod-shaped secretory granules were observed among oval or spherical secretory granules in GH cells of the anterior pituitary gland of musk shrew using the protein A-gold procedure combined with electron microscopy. The rod-shaped and spherical secretory granules were both immunoreactive by the immuno-gold method using antiserum to sheep GH. The rod-shaped secretory granules, which seem to be formed directly from the Golgi vesicles, extend from several hundred to several thousand nm in length. They often touch each other and fuse. The spherical secretory granules are also unique in that they may also fuse with loss of dense contents to leave "empty" circular membrane profiles in the cytoplasm. Both the rod-shaped and spherical secretory granules are secreted from the cell by exocytosis.


Antibody-induced conformational changes result in enhanced avidity of antibodies to different antigenic sites on the tick-borne encephalitis virus glycoprotein.
By the use of monoclonal antibodies we have recently defined eight distinct epitopes on the structural glycoprotein of tick-borne encephalitis (TBE) virus which differ with respect to location, function, or serological specificity (Heinz et al, Virology 126, 525-537, 1983). The present investigation reveals a complex network of interactions between antibodies directed against distinct nonoverlapping epitopes leading to enhanced binding of certain antibodies in the presence of bound second antibodies. The enhancement between antibody pairs can be either unidirectional or bidirectional. In addition, there are domains of predilection, which bind enhanceable antibodies (domain A) whereas others bind antibodies which preferentially induce enhancement (domain B). These domains represent structurally unrelated entities, domain A being sensitive to denaturation and fragmentation and domain B being resistant. Quantitative evaluation of binding data by Scatchard analysis revealed that the observed enhancement phenomenon is due to a two- to sixfold increase of antibody avidity. In the system described, enhancement of antibody binding is not dependent on antibody bivalency since it could also be demonstrated with purified Fab fragments acting either as enhanced or as enhancing antibody. It is therefore concluded that binding of antibodies to certain epitopes on the TBE virus glycoprotein induces conformational changes in distant parts of the molecule which can result in increased avidity of antibodies directed to conformationally changed epitopes. A possible explanation for the origin of this enhancement phenomenon is presented.


Signalling through the yeast MAPK Cell Wall Integrity pathway controls P-body assembly upon cell wall stress.
Post-transcriptional control of mRNA is a key event in the regulation of gene expression. From yeast to human cells, P-bodies are cytoplasmic RNA-protein aggregates that play an essential role in this process, particularly under stress conditions. In this work, we show that in the model yeast Saccharomyces cerevisiae cell wall stress induces the formation of these structures. This effect is dependent on multiple elements in the Cell Wall Integrity (CWI) MAPK signalling pathway, a signal transduction cascade responsible for the maintenance of cell integrity under adverse environmental conditions. Remarkably, P-body assembly requires the catalytic activity of the MAPK of the pathway, Slt2/Mpk1. In accordance with the control exerted by this signalling pathway, the timing of P-body formation is similar to that of the activation of the CWI pathway. Noticeably, mRNAs whose expression is regulated by this pathway localize in P-bodies after the cell is exposed to stress following a temporal pattern coincident with CWI pathway activation. Moreover, when these mRNAs are overexpressed in a mutant background unable to form visible P-bodies, the cells show hypersensitivity to agents that interfere with cell wall integrity, supporting that they play a role in the mRNA lifecycle under stress conditions.


Effects of a New Formulation of Multiple-Action Tear Substitute on Objective Ocular Surface Parameters and Ocular Discomfort Symptoms in Patients with Dry Eye Disease.
Recently, there has been a progressive shift from simple water-adding medications towards complex multi-action combined formulas aimed at disrupting different mechanisms within the dry eye disease (DED) vicious cycle. This study evaluated the efficacy and tolerability of Trimix eye drops (Off Health Italia, Italy), a combination of viscosity-enhancing hyaluronic acid, trehalose, and cationic liposomes comprising stearylamine and phospholipids, in patients with DED. In this prospective, pilot study patients diagnosed with mild to moderate DED were enrolled and treated with Trimix eye drops three times daily for 2 months. Ocular surface workup was performed before (V0) and after therapy (V1) by means of IDRA (SBM Sistemi, Turin, Italy), for the measurement of (i) noninvasive break-up time (NIBUT); (ii) tear meniscus height (TMH); (iii) lipid layer thickness (LLT); (iv) infrared meibography (percentage of meibomian gland loss); (v) bulbar redness (Efron scale). Treatment tolerability was scored on a visual analog scale ranging from 0 (none/not at all) to 100 (much/very) for eight questions. Ocular discomfort symptoms were scored using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Overall, 25 subjects (mean age 60.32 ± 14.55 years) were included in the study. At V1, TMH, NIBUT, and LLT significantly increased compared to V0 (from 0.29 ± 0.06 to 0.46 ± 0.06 mm, 6.34 ± 2.61 to 7.58 ± 2.52 s, and from 63.26 ± 17.15 to 68.42 ± 15.63 nm, respectively; all P < 0.04). Concerning ocular discomfort symptoms, SPEED score significantly improved at V1 (from 16.63 ± 6.32 to 8.30 ± 5.98; P < 0.001); moreover, treatment tolerability was high for all eight items investigated. Two-month treatment with Trimix formulation improved objective signs and subjective symptoms in patients with DED, showing also a good tolerability profile.


Pathway engineering for efficient biosynthesis of violaxanthin in Escherichia coli.
Carotenoids are naturally synthesized in some species of bacteria, archaea, and fungi (including yeasts) as well as all photosynthetic organisms. Escherichia coli has been the most popular bacterial host for the heterologous production of a variety of carotenoids, including even xanthophylls unique to photosynthetic eukaryotes such as lutein, antheraxanthin, and violaxanthin. However, conversion efficiency of these epoxy-xanthophylls (antheraxanthin and violaxanthin) from zeaxanthin remained substantially low. We here examined several factors affecting their productivity in E. coli. Two sorts of plasmids were introduced into the bacterial host, i.e., a plasmid to produce zeaxanthin due to the presence of the Pantoea ananatis crtE, crtB, crtI, crtY, and crtZ genes in addition to the Haematococcus pluvialis IDI gene, and one containing each of zeaxanthin epoxidase (ZEP) genes originated from nine photosynthetic eukaryotes. It was consequently found that paprika (Capsicum annuum) ZEP (CaZEP) showed the highest conversion activity. Next, using the CaZEP gene, we performed optimization experiments in relation to E. coli strains as the production hosts, expression vectors, and ribosome-binding site (RBS) sequences. As a result, the highest productivity of violaxanthin (231 μg/g dry weight) was observed, when the pUC18 vector was used with CaZEP preceded by a RBS sequence of score 5000 in strain JM101(DE3).