A new hypothesis of periodontal homeostasis.
A review of the experimental evidence evidence on marrow inhibition by implanted roots has shown that an inhibitory factor is present in all root surfaces. It is most marked in periodontally diseased roots and least in periodontally healthy roots. It is hypothesized that a "marked" amount would inhibit periodontal cells to the point where they could not resist the destructive effects of plaque, calculus and bacteria. A lesser or "moderate" amount would result in a more resistant periodontium. Finally, little or no inhibitor would also create a periodontium resistant to periodontal destruction but at the same time would remove restraints on the alveolar bone; the result would be invasion of the periodontal space and ankylosis to the root.


NMR studies of molecular conformations in alpha-cyclodextrin.
A new approach for analysis of NMR parameters is proposed. The experimental data set includes scalar couplings, NOEs, and residual dipolar couplings. The method, which aims at construction of the conformational distribution function, is applied to alpha-cyclodextrin in isotropic solution and dissolved in a dilute liquid crystal. An attempt to analyze the experimental data using an average molecular conformation resulted in unacceptable errors. Our approach rests on the maximum entropy method (ME), which gives the flattest possible distribution, consistent with the experimental data. Very good agreement between experimental and calculated NMR parameters was observed. In fact, two conformational states were required in order to obtain a satisfactory agreement between calculated and experimental data. In addition, good agreement with Langevin dynamics computer simulations was obtained.


Both visual and fluorescent sensor for Zn2+ based on quinoline platform.
A fluorescent Zn(2+) sensor 2-(hydroxymethyl)-4-methyl-6-((quinolinyl-8-imino)methyl)phenol (HMQP) based on the 8-aminoquinoline platform has been synthesized. This sensor displays high selectivity, sensitive fluorescence enhancement, strong binding ability, and ratiometric response to Zn(2+) in Tris-HCl (50 mM, pH 7.54), THF-H(2)O (9:1, v/v). And an obvious color change between HMQP and Zn(2+)-MQP(-) can be visually observed by the naked eye. The composition of the complex Zn(2+)-MQP(-) has been found to be 1:2 based on the fluorescence/absorption titration and further confirmed by X-ray crystallography.


Research on the Effects of Drying Temperature on Nitrogen Detection of Different Soil Types by Near Infrared Sensors.
Soil is a complicated system whose components and mechanisms are complex and difficult to be fully excavated and comprehended. Nitrogen is the key parameter supporting plant growth and development, and is the material basis of plant growth as well. An accurate grasp of soil nitrogen information is the premise of scientific fertilization in precision agriculture, where near infrared sensors are widely used for rapid detection of nutrients in soil. However, soil texture, soil moisture content and drying temperature all affect soil nitrogen detection using near infrared sensors. In order to investigate the effects of drying temperature on the nitrogen detection in black soil, loess and calcium soil, three kinds of soils were detected by near infrared sensors after 25 °C placement (ambient temperature), 50 °C drying (medium temperature), 80 °C drying (medium-high temperature) and 95 °C drying (high temperature). The successive projections algorithm based on multiple linear regression (SPA-MLR), partial least squares (PLS) and competitive adaptive reweighted squares (CARS) were used to model and analyze the spectral information of different soil types. The predictive abilities were assessed using the prediction correlation coefficients (RP), the root mean squared error of prediction (RMSEP), and the residual predictive deviation (RPD). The results showed that the loess (RP = 0.9721, RMSEP = 0.067 g/kg, RPD = 4.34) and calcium soil (RP = 0.9588, RMSEP = 0.094 g/kg, RPD = 3.89) obtained the best prediction accuracy after 95 °C drying. The detection results of black soil (RP = 0.9486, RMSEP = 0.22 g/kg, RPD = 2.82) after 80 °C drying were the optimum. In conclusion, drying temperature does have an obvious influence on the detection of soil nitrogen by near infrared sensors, and the suitable drying temperature for different soil types was of great significance in enhancing the detection accuracy.


Easy oxidation and nitration of human myoglobin by nitrite and hydrogen peroxide.
The modification of human myoglobin (HMb) by reaction with nitrite and hydrogen peroxide has been investigated. This reaction is important because NO(2) (-) and H(2)O(2) are formed in vivo under conditions of oxidative and nitrative stress, where protein derivatization has been often observed. The abundance of HMb in tissues and in the heart makes it a potential source and target of reactive species generated in the body. The oxidant and nitrating species produced by HMb/H(2)O(2)/NO(2) (-) are nitrogen dioxide and peroxynitrite, which can react with exogenous substrates and endogenous protein residues. Tandem mass analysis of HMb modified by stoichiometric amounts of H(2)O(2) and NO(2) (-) indicated the presence of two endogenous derivatizations: oxidation of C110 to sulfinic acid (76 %) and nitration of Y103 to 3-nitrotyrosine (44 %). When higher concentrations of NO(2) (-) and H(2)O(2) were used, nitration of Y146 and of the heme were also observed. The two-dimensional gel-electrophoretic analysis of the modified HMbs showed spots more acidic than that of wild-type HMb, a result in agreement with the formation of sulfinic acid and nitrotyrosine residues. By contrast, the reaction showed no evidence for the formation of protein homodimers, as observed in the reaction of HMb with H(2)O(2) alone. Both HMb and the modified HMb are active in the H(2)O(2)/NO(2) (-)-dependent nitration of exogenous phenols. Their catalytic activity is quite similar and the endogenous modifications of HMb therefore have little effect on the reactivity of the protein intermediates.


From rosin to novel bio-based silicone rubber: a review.
Rosin is a characteristic natural renewable resource. In view of the unique hydrogenated phenanthrene ring skeleton structure of rosin, it can be designed and synthesized to modify silicone rubber for improving its mechanical properties, thermal stability, and other properties. In this paper, the research progress of silicone rubber modified by rosin and its derivatives is reviewed, including internal or surface modification of room temperature or high temperature vulcanized silicone rubber. The different chemical modifications and polymerization pathways to obtain bio-based silicone rubber (e.g. rosin-based silicone cross-linking agent, filler compound rosin-based silicone cross-linking agent, rosin-based polymer, and rosin quaternary ammonium salt bifunctional antibacterial coating) are discussed and its research prospect is reviewed. Overall, the present review article will provide a quantitative experimental basis for rosin to produce bio-renewable multifunctional silicone rubber to increase our level of understanding of the behavior of this important class of silicone rubber and other similar bio-based polymers.


Cervical necrotizing fasciitis: descriptive, retrospective analysis of 59 cases treated at a single center.
To provide retrospective, descriptive information on patients with cervical necrotizing fasciitis treated at a single center during the years 1998-2014, and to evaluate the outcome of a newly introduced treatment strategy. Retrospective analysis of clinical data obtained from medical records. Mortality, pre-morbidity, severity of illness, primary site of infection, type of bacteria, time parameters. The observed 3-month mortality was 6/59 (10 %). The most common initial foci of the infection were pharyngeal, dental or hypopharyngeal. The most common pathogen was Streptococcus milleri bacteria within the Streptococcus anginosus group (66 % of the cases). Using a combined treatment with early surgical debridement combined with hyperbaric oxygen treatment, it is possible to reduce the mortality rate among patients suffering from cervical necrotizing fasciitis, compared to the expected mortality rate and to previous historical reports. Data indicated that early onset of hyperbaric oxygen treatment may have a positive impact on survival rate, but no identifiable factor was found to prognosticate outcome.


Sequence-, tissue-, and delivery-specific targeting of RNA during post-transcriptional gene silencing.
Transgenic Nicotiana benthamiana plants expressing an untranslatable version of the coat protein (CP) gene from the Tamarillo mosaic virus (TaMV) were either resistant to TaMV infection or recovered from infection. These phenotypes were the result of a post-transcriptional gene silencing (PTGS) mechanism that targeted TaMV-CP sequences for degradation. The TaMV-CP sequences were degraded when present in the wild-type TaMV potyvirus, in transgene mRNA, or in chimeric viral vectors based on White clover mosaic virus. The more efficiently targeted region was mapped to a 134-nt segment. Differences were observed in the efficiency of targeting during cell-to-cell and long-distance movement of the chimeric viruses. However, the TaMV-CP sequences do not appear to be targeted for degradation when delivered by biolistics.


Investigation of the stability of medicinal additives in animal feedingstuffs to prepare reference feeds.
The stability of several medicinal additives in cattle, pig and poultry feeds has been monitored. The feeds were stored at various temperatures under different conditions; processes such as freeze-drying, gamma-irradiation and pelletization were also applied. The medicinal additives appeared to be more stable in the feeds stored at reduced temperatures and under conditions that totally exclude light. Processing of feeds and storage at elevated temperature appeared to reduce the content of the medicinal additives examined.


Assessment of Pain Intensity in Patients with Dentin Hypersensitivity After Application of Prophylaxis Paste Based on Calcium Sodium Phosphosilicate Formula.
One of many functions of the pulp-dentin complex is sensory function. Acute, situated, receding pain after the cessation of the stimulus action is called dentin pain. Dentin hypersensitivity has been described as one of the most painful and least successfully treated chronic ailments of teeth. The aim of this research was the clinical evaluation of the effectiveness of professional polishing paste containing calcium sodium phosphosilicate formula (NovaMin) in eliminating dentin hypersensitivity after a single application. The study comprised 92 teeth with dentin hypersensitivity diagnosed on the basis of history and clinical examination. The pain reaction of exposed dentine was induced by tactile and dehydrating stimuli, asking patients to assess the severity of pain on the VAS scale. Clinical trial and survey were carried out twice: before and 1 week after the application of the polishing paste. After the application of the examined paste, the percentage of teeth reacting with a severe pain to the touch of the probe decreased from 16.3% to 4.3%, and with a moderate pain from 42.4% to 12%. Examination after applying dehydrating stimulus a week after carrying out the application showed a decrease in the proportion of teeth with strong pain from 28.3% to 0% and moderate pain from 38% to 15.2%. The lack of pain increased from 12% to about 50%. The use of prophylactic professional paste with NovaMin formula in in-office procedure provides the reduction of dentin hypersensitivity noticeable by 1 week after application.


Fibrillogenic amylin evokes islet beta-cell apoptosis through linked activation of a caspase cascade and JNK1.
Fibrillogenic human amylin elicits pancreatic beta-cell apoptosis that may contribute to development of type-2 diabetes. Here, we demonstrated that activation of a caspase cascade is necessary for induction of apoptosis by fibrillogenic amylin variants in two pancreatic beta-cell lines. Human amylin, as well as truncated 8-37human amylin, evoked sequential activation of caspases-8 and -3, and apoptosis, whereas non-beta-sheet forming and non-fibrillogenic homologs, such as [25,28,29triprolyl]human amylin, did not, implying that the beta-sheet conformer is required for human amylin-induced caspase activation. Significant inhibition of apoptosis was evoked by a selective caspase-1 inhibitor, indicating that caspase-1 is also essential for activation of the caspase cascade. Furthermore, we showed that specific jnk1 antisense oligonucleotides, which suppress phospho-JNK1 expression, effectively decreased human amylin-induced activation of c-Jun. Studies of the interplay between the caspase cascade and the JNK pathway showed that both apoptosis and caspase-3 activation were suppressed by treatment with a JNK inhibitor and by transfection of antisense jnk1 oligonucleotides or antisense-c-jun, whereas a selective inhibitor of caspases-1 and -3 prevented apoptosis but not c-Jun activation. Thus, the JNK1 activation preceded activation of caspases-1 and -3. However, selective JNK inhibition had no effect on caspase-8 activation, and selective caspase-8 inhibition only partially suppressed apoptosis and c-Jun activation, indicating that caspase-8 may partially act upstream of the JNK pathway. Our studies demonstrate a functional interaction of a caspase cascade and JNK1. Fibrillogenic amylin can evoke a JNK1-mediated apoptotic pathway, which is partially dependent and partially independent of caspase-8, and in which caspase-3 acts as a common downstream effector.


Saccharomyces Cerevisiae as an Untapped Source of Fungal Chitosan for Antimicrobial Action.
Despite being widely available, Saccharomyces cerevisiae has not been widely explored for direct extraction of chitosan biopolymer for antimicrobial applications. In our study, S. cerevisiae from Baker's yeast and Aspergillus niger from moldy onion extracts are studied as alternative sources of chitosan; and S cerevisiae chitosan tested for antimicrobial efficacy. The properties of S. cerevisiae chitosan are compared with moldy onion chitosan and shrimp chitosan extracted from shrimp shells. Chitosan extracted from S. cerevisiae is tested for antimicrobial efficacy against Staphylococcus Aureus. The maximum yields of fungal chitosan are 20.85 ± 0.35 mg/g dry S. cerevisiae biomass at 4th day using a culture broth containing sodium acetate, and 16.15 ± 0.95 mg/g dry A. niger biomass at 12th day. The degree of deacetylation (DD%) of the extracted fungal chitosan samples from S. cerevisiae and A. niger is found to be 63.4%, and 61.2% respectively, using Fourier Transform Infrared Spectroscopy. At a concentration of 2 g/L, S. cerevisiae chitosan shows the maximum inhibition zone diameter of 15.48 ± 0.07 mm. Baker's yeast S cerevisiae biomass and A. niger from moldy onions has not been previously explored as a source of extractible fungal chitosan. This study gives insight that S. cerevisiae and A. niger from agricultural or industrial wastes could be a potential biomass source for production of the chitosan biopolymer. The S. cerevisiae chitosan displayed effective antimicrobial properties against S aureus, indicating the viablitiy of S cerevisae as a resource for extraction of high-quality chitosan.


Barriers and facilitators to interhospital transfer of acute pulmonary embolism: An inductive qualitative analysis.
Interhospital transfer (IHT) of patients with acute life-threatening pulmonary embolism (PE) is necessary to facilitate specialized care and access to advanced therapies. Our goal was to understand what barriers and facilitators may exist during this transfer process from the perspective of both receiving and referring physicians. This qualitative descriptive study explored physician experience taking care of patients with life threatening PE. Subject matter expert physicians across several different specialties from academic and community United States hospitals participated in qualitative semi-structured interviews. Interview transcripts were subsequently analyzed using inductive qualitative description approach. Four major themes were identified as barriers that impede IHT among patients with life threatening PE. Inefficient communication which mainly pertained to difficulty when multiple points of contact were required to complete a transfer. Subjectivity in the indication for transfer which highlighted the importance of physicians understanding how to use standardized risk stratification tools and to properly triage these patients. Delays in data acquisition were identified in regards to both obtaining clinical information and imaging in a timely fashion. Operation barriers which included difficulty finding available beds for transfer and poor weather conditions inhibiting transportation. In contrast, two main facilitators to transfer were identified: good communication and reliance on colleagues and dedicated team for transferring and treating PE patients. The most prominent themes identified as barriers to IHT for patients with acute life-threatening PE were: (1) inefficient communication, (2) subjectivity in the indication for transfer, (3) delays in data acquisition (imaging or clinical), and (4) operational barriers. Themes identified as facilitators that enable the transfer of patients were: (1) good communication and (2) a dedicated transfer team. The themes presented in our study are useful in identifying opportunities to optimize the IHT of patients with acute PE and improve patient care. These opportunities include instituting educational programs, streamlining the transfer process, and formulating a consensus statement to serve as a guideline regarding IHT of patients with acute PE.


Extratympanic manometry in man. Clinical and experimental investigations of the acoustic stapedius and tensor tympani contractions in normal subjects and in patients.
New ideas and inspirations for future human investigations have emerged from the experience obtained in this study. These investigations ought to be performed for both scientific and clinical reasons. It is the author's opinion that the ETM method is extremely useful and valuable. The author intends to continue the human investigations if proper conditions are available. The ETM equipment can also be further improved for scientific and special clinical investigations. For normal clinical practice a more "simplified" ETM equipment should be developed. Clinical investigations concerning the diagnosis of brain stem disorders and the selection of noise susceptible persons will be two of the primary clinical tasks.


[Mental fatigue assessment based on physiological signals].
To assess mental fatigue by noninvasive monitoring of the physiological signals. The changes in the physiological parameters including the electrodermal activity, heart rate and heart rate variability were analyzed in 14 subjects performing the reaction-time tasks when fatigue and changes in the reaction time occurred. The average skin conductance level, average heart rate, and heart rate variability parameters including the total power density, percentage of the very low power density, percentage of high power density all differed significantly between the sober state and the mental fatigue state. Monitoring the physiological parameters including the electrodermal activity, heart rate and heart rate variability is a noninvasive, effective and practical approach to mental fatigue assessment.


Basin bifurcations in quasiperiodically forced coupled systems.
We study the effect of quasiperiodic forcing on a system of coupled identical logistic maps. Upon a variation of system parameters, a variety of different dynamical regimes can be observed, including phenomena such as bistability and multistability. At the bifurcation to bistability, in a manner reminiscent of attractor expansion at interior crises, there is an abrupt change in the size of attractor basins. In the bistable region, attractor basins undergo additional bifurcations wherein holes and islands are created within the basins when system parameters change. These can be understood by examining critical surfaces for the coupled system.


Purification and characterization of the thyrotropin-releasing-hormone-degrading ectoenzyme.
The membrane-bound enzyme which catalyzes the degradation of thyrotropin-releasing hormone (TRH; Glp-His-Pro-NH2) could be released from membranes of rat and pig brain by treatment with trypsin under very mild incubation conditions. The solubilized enzyme was purified 200,000-fold, with an overall yield of 20%, by conventional chromatographic methods. The enzyme preparation appeared to be electrophoretically homogenous since SDS/PAGE analysis revealed a single band with a molecular mass of 116,000 Da. By gel-filtration chromatography, a molecular mass of 230,000 Da was estimated, suggesting that the enzyme consists of two identical subunits. The enzyme could be identified as a glycoprotein by lectin-binding analysis and by the reduction of the molecular mass to 97,000 Da upon treatment of the denatured enzyme with endoglycosidase-F/N-glycosidase F. In its native form, however, the enzyme was only partially deglycosylated and retained full enzymatic activity. In addition to TRH, the enzyme also hydrolyzed L-5-oxoprolyl-beta-naphthylamide, and thus a convenient fluorimetric assay could be established to determine high enzyme activities. The hydrolysis of both substrates was found to obey Michaelis-Menten kinetics, but considerable differences in the respective Km and Vmax values were noticed.


Plasma membrane depolarization and disturbed Na+ homeostasis induced by the protonophore carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazon in isolated nerve terminals.
The effect of the protonophore carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazon (FCCP) was studied on the intracellular [Na+], pH, and plasma membrane potential in isolated nerve terminals. FCCP induced a rise of [Na+]i at, and even below, the concentrations (0.025-1 microM) in which it is usually used in intact cells to eliminate Ca2+ uptake by mitochondria. The FCCP-induced increase of [Na+]i correlates with a fall in both the ATP level and the ATP/ADP ratio. In addition, a sudden rise of the intracellular proton concentration ([H+]i) from 83 +/- 0.4 to 124 +/- 0.7 nM was observed on the addition of FCCP (1 microM). Parallel with the rise in [H+]i, an abrupt depolarization was detected, followed by a slower decrease in the plasma membrane potential. Both the extent of the pHi change and the fast depolarization of the plasma membrane were proportional to the proton electrochemical gradient across the plasma membrane; when this gradient was increased, greater depolarization was detected. The slower decrease of the membrane potential after the fast initial depolarization was abolished when the medium contained no Na+. It is concluded that FCCP (1) gives rise to a depolarization by setting the plasma membrane potential close to the proton equilibrium potential and (2) enhances the intracellular [Na+] as a consequence of an insufficient ATP level and ATP/ADP ratio to fuel the Na+,K+/ATPase. Because both disturbed Na+ homeostasis and plasma membrane depolarization could profoundly interfere with Ca2+ homeostasis in the presence of protonophores, consideration given to these alterations may help to clarify the cellular Ca2+ sequestration processes.


[Status and advances of long-acting factor Ⅷ].
Current treatment for hemophilia A is based on replacement therapy that is the most effective method by using recombinant clotting factor FⅧ (rFⅧ). Although the safety and effectiveness of replacement therapy has been proved by clinical practice for the last decades, FⅧ products are temporally limited because of a short half-life and requiring prophylactic injections frequently for most patients, usually three times per week or every other day. Frequent intravenous injection not only brings physical pain to the patient, but also produces FⅧ antibodies that seriously affect the treatment effect. In this paper, we review the present status, research progress and main problems of the long-acting recombinant factor Ⅷ.


Moving Beyond the Pandemic: Insights from a Shared Experience.
For over two years the resilience of humanity was tested with the coronavirus outbreak. At its outset the scientific community rallied and did its very best to disseminate accumulating knowledge in real time to contain the outbreak. Sobering lessons were learned in managing such a global crisis. Critical care anesthesiologists in particular were instrumental as decision makers and their insight is reflected in a review of how we may be better prepared in the future should another virus spread with such scale and severity. Members of the Society of Critical Care Anesthesiologists contribute to a special article in this issue that focuses on several broad themes that emerged from managing the pandemic. These include large scale decision making in health care systems, clinical management of a new disease, resource management with conversion of operating rooms to intensive care units, and health care provider well-being. These considerations are summarized in this infographic. It is heartening to see an article and an accompanying editorial in this issue that address what we have learned from our collective experience. It is a testament to the will of the scientific community and health care providers to evolve and overcome, to move beyond discouragement and prevail.


The Diagnosis of Acute Renal Allograft Rejection Using T-lymphocyte Subsets in the Peripheral Blood: A Better Test Now?
Measuring the T-lymphocyte subsets CD4/CD8 ratio is known to be useful in the early diagnosis of acute rejection. A ratio of 1.3 or more is said to indicate the presence of acute rejection, but the sensitivity and specificity rates of the test are too low to render it of diagnostic value. We revisited this test on twenty-three renal allograft recipients who developed graft dysfunction within the first three months following transplantation. All cases were investigated thoroughly to identify the cause of graft dysfunction. Two groups of patients were identified. Group 1: patients confirmed to have acute rejection as the cause of graft dysfunction (13 patients); and group 2: patients found to have other causes of graft dysfunction (10 patients). Results of subsets with cluster of differentiation ratio CD4/CD8 were correlated with incidence of acute rejection. Of the 13 patients with acute rejection 10 revealed a CD4/CD8 ratio more than 1.7, while in the other three CD4/CD8 ratio was less than 1.7. In the second group of 10 patients in whom the cause of graft dysfunction was not acute rejection, the CD4/CD8 ratio was less than 1.7 in all cases. Our study indicates that T-lymphocyte subset ratio is useful in diagnosing acute rejection with a sensitivity and specificity of 81% and 100% respectively when the cutoff point is taken as 1.7. Studies with larger series of patients are needed to confirm this observation.


Self-reported care needs of Dutch homeless people with and without a suspected intellectual disability: a 1.5-year follow-up study.
Cognitive impairment is a prevalent problem among the homeless and seems related to more psychosocial problems. However, little is known about the care needs of the subgroup of homeless people with an intellectual disability compared to those without an intellectual disability and how their care needs develop over time. This study explores self-reported care needs within a broad range of life domains among Dutch homeless people with and without a suspected intellectual disability to gain insight into the transition of self-reported care needs from baseline to follow-up in both subgroups. This longitudinal study is part of a cohort study among homeless people who had been accepted for an individual programme plan in four major Dutch cities. The initial cohort consisted of 513 participants who were interviewed in 2011. At 1.5-year follow-up, 336 participants (65.5%) were also interviewed and screened for intellectual disability. Of these participants, 31% (95% CI 26.2-36.1) had a suspected intellectual disability. For both groups, between baseline and follow-up, the number of 'unmet care needs' decreased significantly and the number of 'no care needs' increased significantly, while at follow-up, participants with a suspected intellectual disability reported 'no care needs' on significantly fewer life domains than those without a suspected intellectual disability (mean numbers 16.4 vs. 17.5). Between baseline and follow-up, 'met care needs' decreased significantly on housing for both groups, and increased on finances and dental care for participants with a suspected intellectual disability. At follow-up, participants with a suspected intellectual disability more often preferred housing support available by appointment than those without a suspected intellectual disability. These findings suggest that homeless people who had been accepted for an individual programme plan with a suspected intellectual disability have care needs for a longer period of time than those without a suspected intellectual disability. Providing care to homeless people with a suspected intellectual disability might require ongoing care and support, also after exiting homelessness. Support services should take this into account when considering their care provision and planning of services.


Healthcare Applications of pH-Sensitive Hydrogel-Based Devices: A Review.
pH-sensitive hydrogels have been developed greatly over the past few years. This has been possible due to the synthesis of new hydrogel systems with increased sensitivity - a sensitivity of up to 10-5 pH units has already been established. Recently, pH-sensitive hydrogels have shown to be very useful in biomedical applications, such as targeted cancer treatment and treatment of skin lesions. Prolonged drug release has been made available through the use of such hydrogels. The synthesis of pH-sensitive hydrogels is also quick and cost-effective. This review presents a background on the properties of pH-sensitive hydrogels and discusses some of the hydrogels with different sensitivity ranges and their possible applications. A range of synthesis processes have also been briefly introduced along with the fabrication of different structures such as microcantilevers and contact lenses.


Esophageal atresia. Prognostic factors and contribution of preoperative telescopic endoscopy.
In recent years, the surgical correction of esophageal atresia with distal tracheoesophageal fistula (TEF) has become increasingly successful. However, there remains a group of high-risk patients with specific anatomical abnormalities in whom the mortality remains appreciable. These associated disorders include cardiac, renal, and chromosomal anomalies as well as severe respiratory distress syndrome. These factors, rather than low birth weight or early gestational age, are primarily responsible for surgical mortality. Preoperative telescopic bronchoscopy has been a useful adjuvant confirming the diagnosis, identifying unusual variants, and permitting the proper anatomic placement of the endotracheal tube. A Fogarty balloon catheter can be passed bronchoscopically into the distal TEF in patients with severe respiratory distress syndrome to occlude the fistula and facilitate effective positive pressure ventilation. Thirty-two patients were treated for esophageal atresia among whom 28 had esophageal atresia with distal TEF, three had esophageal atresia alone, and one had esophageal atresia with proximal TEF. The higher-risk group comprised those with severe respiratory insufficiency as evidenced by a room air paO2 of less than 60 mmHg; this group accounted for nine of the ten deaths in the total series. There was one late death following surgical correction. In summary, in the absence of severe respiratory insufficiency or associated life-threatening congenital anomalies, the results of surgical correction for esophageal atresia are remarkably good and survival in this group approximates 100%.


Choreography of the squid's "nuptial dance".
A mass spawning of squid resembles, at first glance, a chaotic "nuptial dance" (1). But for the first time, we have applied 3-D, radio-linked acoustic positioning (RAP) to this confusing process, and our early results now reveal a choreography that is, in fact, well organized in time and space. Remote tracking with RAP of individual Loligo vulgaris reynaudii off South Africa has provided insights into the daily sequence of behaviours that lead these animals to aggregate for sexual selection. Each dawn, the squid navigate for several kilometers, towards the shore, to small, well-defined zones near egg beds on the substrate. After several hours of circling above the egg beds, a pelagic, 3-D lek-like aggregation of large males forms: females are drawn in, and the aggregation condenses as the females and males pair, mate, and lay eggs. Smaller "sneaker males" remain on the periphery of the mating arena and, from this station, attempt extra-pair copulations (EPCs). The mating system of squids is thus unexpectedly complex, rivaling those of mammals and birds (2, 3). Commercial squid-jigging fishermen in South Africa have recently been attracted to the spawning grounds, and they have been successful. Moreover, their activities may be selective for large males. Thus, attention should be devoted to ensuring that such targeted fishing does not alter the characteristics of squid population genetics. Remote tracking and video observations, in combination with genetic analyses, may offer a new opportunity to monitor mating effort and reproductive success, and thus to manage the fishery.


Human ocular pursuit during the transient disappearance of a visual target.
During the course of pursuing a moving target there are often periods of transient disappearance as it moves behind objects and surfaces. In experimental settings, eye velocity decays rapidly on the extinction of a moving target. However, eye velocity does not decay to zero if there is an expectation the target will reappear further along its trajectory. Increasing eye velocity to coincide with target reappearance could minimize the developing velocity error, but it remains to be empirically verified whether this can be achieved. The aim of the present study was to examine the influence of stimulus predictability, target velocity, and interstimulus interval (ISI) on ocular pursuit during the transient disappearance of a visual target. We confirmed that subjects (n = 9) did not maintain eye velocity close to target velocity for the duration of the ISI. In general, after an initial reduction in eye velocity the majority of subjects (n = 7) exhibited a significant increase before target reappearance. The timing of the velocity increase was not influenced by target velocity, stimulus predictability, or ISI. Consequently, for the 900-ms ISI the increase occurred too early and the eye was decelerating at the moment of target reappearance. These results are consistent with a reduction in gain being applied to the visuomotor drive when the target disappeared, followed by a reactivation in expectation of target reappearance. We modeled this process such that gain was modulated within a reafferent feedback system, hence preserving its output in the absence of negative visual feedback and enabling an anticipatory increase in eye velocity before expected target reappearance.


China's syphilis epidemic: epidemiology, proximate determinants of spread, and control responses.
China has experienced an increase in the incidence and prevalence of syphilis that is especially remarkable since this infection was virtually eradicated in the country 50 years ago. The purpose of this analysis is to provide an overview of recent literature on syphilis proximate determinants and potential public health responses. Per capita syphilis burden is greatest in coastal urban China. There are a number of biological, demographic, geographic, and behavioral/social proximate determinants of syphilis spread that distinguish the Chinese syphilis epidemic. These determinants portend the need for intensified syphilis control efforts, including: comprehensive testing and treatment; integration with HIV, sexually transmitted infection, and antenatal services; scale-up of novel rapid syphilis test technology, and multisectorial support. The Chinese central government recently announced a 10-year syphilis plan to provide clear expectations for evaluating the success of local syphilis control programs and integration with HIV testing programs. Further research is needed to understand the social and behavioral determinants driving the spread of syphilis.


Have the year 2000 neonatal resuscitation program guidelines changed the delivery room management or outcome of meconium-stained infants?
To study the impact of neonatal resuscitation program (NRP) guidelines on delivery room (DR) management of infants born through meconium-stained amniotic fluid (MSAF). A retrospective study of all term (>or=37 weeks) infants born through MSAF was performed. Patients were divided into two periods: pre year 2000 NRP and post year 2000 NRP. Meconium consistency, APGAR scores and intubation (INT) for suctioning and respiratory outcome were recorded. Groups were analyzed using chi (2) tests and stepwise logistic regression. The incidence of MSAF remained constant in period 1 (13.6%) and period 2 (13.1%) while the proportion of infants intubated fell from 67 to 41% (p<0.001). The incidence of meconium aspiration and nonspecific respiratory distress did not differ between groups. Since the implementation of year 2000 NRP guidelines, the rate of DR INT for tracheal suctioning has fallen significantly without a change in overall respiratory complications. Results of this study support the efficacy of year 2000 NRP recommendations.


Expectations of an Online-Self-Management Program for Rheumatoid Arthritis.
This qualitative descriptive study aimed to explore expectations of patients and healthcare experts for an online self-management program for rheumatoid arthritis. Participants were recruited from rheumatology clinics, medical centers, and universities in Taiwan. Individual face-to-face, semi-structured interviews were conducted with patients (n = 16) and healthcare experts (n = 7). Content analysis of the interview data resulted in five subthemes for expectations of an online self-management program: information about how the disease trajectory would impact future health status, availability of opportunities for self-monitoring, opportunities to interact with fellow patients and healthcare providers, simplicity and ease-of-use of the program, and methods to facilitate patient-motivation. These subthemes formulated two overarching themes: content and format. An online self-management program for patients with rheumatoid arthritis should provide evidence-based information about disease variables and behaviors aligned with the specific needs of the individual and adopt strategies that encourage and increase motivation and confidence.


Transport and fate of nitrate in a glacial outwash aquifer in relation to ground water age, land use practices, and redox processes.
A combination of ground water modeling, chemical and dissolved gas analyses, and chlorofluorocarbon age dating of water was used to determine the relation between changes in agricultural practices, and NO3- concentrations in ground water of a glacial outwash aquifer in west-central Minnesota. The results revealed a redox zonation throughout the saturated zone with oxygen reduction occurring near the water table, NO3- reduction immediately below it, and then a large zone of ferric iron reduction, with a small area of sulfate (SO4(2-)) reduction and methanogenesis (CH4) near the end of the transsect. Analytical and NETPATH modeling results supported the hypothesis that organic carbon served as the electron donor for the redox reactions. Denitrification rates were quite small, 0.005 to 0.047 mmol NO3- yr(-1), and were limited by the small amounts of organic carbon, 0.01 to 1.45%. In spite of the organic carbon limitation, denitrification was virtually complete because residence time is sufficient to allow even slow processes to reach completion. Ground water sample ages showed that maximum residence times were on the order of 50 to 70 yr. Reconstructed NO3- concentrations, estimated from measured NO3- and dissolved N gas showed that NO3- concentrations have been increasing in the aquifer since the 1940s, and have been above the 714 micromol L(-1) maximum contaminant level at most sites since the mid- to late-1960s. This increase in NO3- has been accompanied by a corresponding increase in agricultural use of fertilizer, identified as the major source of NO3- to the aquifer.


How Anticipated and Experienced Stigma Can Contribute to Self-Stigma: The Case of Problem Gambling.
The degree to which anticipated and experienced public stigma contribute to self-stigma remains open to debate, and little research has been conducted into the self-stigma of problem gambling. This study aimed to examine which aspects of anticipated and experienced stigma (if any) predict the anticipated level of public stigma associated with problem gambling and the degree of self-stigma felt by people experiencing problem gambling. An online survey of 177 Australians experiencing problem gambling examined whether aspects of the public characterization of problem gambling, anticipated reactions to problem gamblers, and experiences of devaluation and discrimination predicted anticipated level of public stigma and self-stigma. The study found that self-stigma increases with expectations that the public applies a range of negative stereotypes to people with gambling problems, holds demeaning and discriminatory attitudes toward them, and considers them to lead highly disrupted lives. These variables directly predicted anticipated level of public stigma and indirectly predicted self-stigma. These findings lend weight to conceptualizations of self-stigma as an internalization of actual or anticipated public stigma. They also highlight the need for stigma reduction efforts, particularly those that lower negative stereotyping and prejudicial attitudes, to improve currently low rates of help-seeking amongst people with gambling problems.


Modular synthesis of sulfonyl benzoheteroles by silver-catalyzed heteroaromatization of propargylic alcohols with p-toluenesulfonylmethyl isocyanide (TosMIC): dual roles of TosMIC.
A new silver-catalyzed heteroaromatization of propargylic alcohols with p-toluenesulfonylmethyl isocyanide (TosMIC) has been developed that provides an efficient and modular approach to sulfonyl benzoheteroles. For the first time, TosMIC plays a dual role in one reaction: sulfonyl source and ligand. An unprecedented deoxysulfonylation/hydration/condensation reaction pathway is disclosed.


Knowledge and practice and attitude toward cupping therapy among physicians in Sheikh Khalifa medical city.
Complementary medicine (CM) is gaining popularity worldwide. According to the 2019 World Health Organization global report on traditional and complementary medicine (T&CM), 80% of member states acknowledged practicing T&CM. In the United Arab Emirates, T&CM practice prevalence in 2012 was 20-39%. These trends highlight physicians' need for knowledge on CM, such as cupping therapy. This study aims to assess knowledge, practice, and attitude toward cupping therapy (CT) among physicians in Sheikh Khalifa medical city (SKMC). A cross-sectional study was conducted from September 2020 to March 2021 among the physicians of SKMC. The survey was carried out using an online questionnaire. The questionnaire included four sections: socio-demographics, knowledge of physicians toward cupping therapy, physicians' attitude toward cupping therapy, and physicians' practice toward cupping therapy. SPSS version 28 was used for data analysis. Data were reported in frequencies and percentages. A P value of <0.05 is the level of statistical significance. The response rate was 83%. Among the 154 participants, 67.5% had adequate knowledge of CT, 66.9% showed a positive attitude, and 31.2% reported good practice toward CT. Individuals below 40 years reported significantly lesser knowledge than individuals over 40 years (p = 0.035, OR 0.49 [0.246-0.998]). Over 80% of physicians concur that cupping therapy can be used to treat and manage low back pain, joint discomfort, headache, migraine, and anxiety. The majority of physicians believe that education regarding cupping therapy is required. Most physicians had adequate knowledge and a positive attitude toward cupping therapy.


The effect of tracheostomy performed within 72 h after traumatic brain injury.
The optimal timing of tracheostomy in patients with traumatic brain injury (TBI) remains unclear. The purpose of this study was to examine the effects of tracheostomy performed within 72 h after admission. In this retrospective cohort study, the authors reviewed the data for a series of 120 consecutive patients who underwent tracheostomy after suffering TBI with an Abbreviated Injury Scale (AIS) score of ≥4. The exclusion criteria were as follows: age <18 years, severe chest injury with an AIS score of ≥4, and a requirement for intubation because of upper airway obstruction. Patients who underwent tracheostomy ≤72 h and >72 h after admission were classified into early group and control groups, respectively. The duration of mechanical ventilation, length of stay (LOS) in intensive care unit (ICU), incidence of pneumonia, adverse event rate, unnecessary tracheostomy and outcomes were compared between the two groups. Of the 120 patients, 29 were excluded from the study, 40 were classified into the early group, and 51 were classified into the control group. The duration of mechanical ventilation and LOS in ICU were significantly less in the early group than in the control group. The 30-day mortality rates were 3% and 8% for the early and control groups, respectively. There was no significant difference in the adverse event rate, incidence of pneumonia, unnecessary tracheostomy rate and the rate of favorable outcome between groups. The results of this study suggest that the performance of tracheostomy within 72 h of admission may decrease the duration of mechanical ventilation and LOS in ICU, with acceptable mortality and morbidity rates.


In vitro ozone exposure inhibits mitogen-induced lymphocyte proliferation and IL-2 production.
Human blood mononuclear cells were exposed to ozone in vitro and thereafter analyzed for competence in mitogen-induced proliferation as well as IL-1 and IL-2 production. Proliferative responses induced by phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) were all depressed in lymphocytes exposed to an ozone concentration of 1 ppm for 4-6 h. The response to PWM was most sensitive to the ozone effect (38% suppression); responses to Con A and PHA were suppressed to a lesser extent, 23% and 18%, respectively, and were not significantly different from each other. PWM responses were affected at an ozone concentration as low as 0.1 ppm; however, no suppression of Con A-induced proliferation was seen below 0.18 ppm or of PHA-induced proliferation below 0.5 ppm. When lymphocytes and monocytes were exposed separately to ozone and then mixed back with control air-exposed monocytes or lymphocytes, both cell types appeared to be affected and the functional defects caused by the pollutant were additive. Monocyte IL-1 production induced by endotoxin was not affected by ozone exposure, while surface expression of HLA-DR on exposed monocytes was reduced by 40% 24 h after exposure. Moreover, lymphocytes exposed to ozone produced 46% less IL-2 while expressing similar surface density of IL-2 receptors. Taken together, these results show that exposure to ozone has distinct adverse effects on lymphocytes and monocytes, both of which are important in local immune defenses in the lung.


Cultivating ethics consultation: commentary on "The development of a clinical ethics consultation service in a community hospital.
Simpson's article [in this issue, p. 124-130] provides us with needed data about the development and utilization of an ethics consultation service in a community hospital. It makes clear, however, how much further we have to go in developing guiding standards for practitioners and institutions. We need to learn much more about the effectiveness of ethics consultation in meeting well-defined goals and producing desired processes and outcomes before standards for credentials and accountability have a sound empirical basis.


Shorter than short-chain: Very short-chain chlorinated paraffins (vSCCPs) found in wildlife from the Yangtze River Delta.
Very short-chain chlorinated paraffins (vSCCPs, C6-9) occurred in 94% of wildlife samples from the Yangtze River Delta (YRD), China, with CnClm comparable to that of a local CP product, CP-52. Therefore, we determined the content of vSCCPs in CP-52 using a mathematical deconvolution technique. Then with CP-52 and several other reference standards, vSCCPs together with short-, medium-, and long-chain CPs were quantified in 21 wildlife species from an artificial wetland ecosystem and a freshwater ecosystem in the YRD. Concentrations of vSCCPs ranged from 2.6 to 8400 ng/g lipid. These concentrations were 1.2-380 fold lower than SCCPs, but were significantly correlated with those of SCCPs. vSCCP concentrations were comparable to or higher than reported for brominated flame retardants in the same samples. Bioaccumulation tendency of vSCCPs was identified in two benthic species, indicating congener-specific accumulation of vSCCPs in the environment.


Arrayed primer extension: a robust and reliable genotyping platform for the diagnosis of single gene disorders: beta-thalassemia and thiopurine methyltransferase deficiency.
Mutation screenings, which were conventionally carried out individually because of different assay conditions, are usually time consuming and not cost effective. Using microarray technology, simultaneous molecular diagnosis of multiple mutations on a single platform is possible. To evaluate this idea, we developed a DNA chip platform to simultaneously detect 23 mutations of the beta-globin gene and 9 mutations of thiopurine methyltransferase (TPMT) gene based on the principle of arrayed primer extension (APEX). A blinded test consisting of 200 DNA samples with known genotypes was performed to validate this strategy. High genotyping accuracy of 97.3% and 100% for beta-globin and TPMT genes, respectively, were achieved. Further analysis on the fluorescent intensity demonstrated clear separation between the real signal and the background noise, which enabled us to set two cutoff values (V(lower) = 4.0 and V(upper) = 12.0) to determine the genotype quantitatively. Our results showed that APEX is a highly reliable genotyping strategy to detect mutations that cause beta-thalassemia or TPMT enzyme deficiency.


The extracellular matrix of the gastrointestinal tract: a regenerative medicine platform.
The synthesis and secretion of components that constitute the extracellular matrix (ECM) by resident cell types occur at the earliest stages of embryonic development, and continue throughout life in both healthy and diseased physiological states. The ECM consists of a complex mixture of insoluble and soluble functional components that are arranged in a tissue-specific 3D ultrastructure, and it regulates numerous biological processes, including angiogenesis, innervation and stem cell differentiation. Owing to its composition and influence on embryonic development, as well as cellular and organ homeostasis, the ECM is an ideal therapeutic substrate for the repair of damaged or diseased tissues. Biologic scaffold materials that are composed of ECM have been used in various surgical and tissue-engineering applications. The gastrointestinal (GI) tract presents distinct challenges, such as diverse pH conditions and the requirement for motility and nutrient absorption. Despite these challenges, the use of homologous and heterologous ECM bioscaffolds for the focal or segmental reconstruction and regeneration of GI tissue has shown promise in early preclinical and clinical studies. This Review discusses the importance of tissue-specific ECM bioscaffolds and highlights the major advances that have been made in regenerative medicine strategies for the reconstruction of functional GI tissues.


[A simple method for determination of flurbiprofen in human plasma by gas chromatography-mass spectrometry].
A method for gas chromatograph-mass spectrometric assay has been developed for the quantitation of flurbiprofen in human plasma. Extraction or condensing procedure was not required and the method reduced time involved in sample preparation. The analytes were separated on the fused-silica capillary column. The operating conditions were: injector, 250 degrees C; detector, 300 degrees C; and column, 50-280 degrees C. The total gas flow-rate of helium (carrier) was 50 ml.min-1 and the pressure of column inlet was 100-200 kPa. The retention time was 18.1 min and the limit of quantitation was 0.5 microgram.ml-1. This method provides an easy and simple method for the detection of flurbiprofen.


[The adjuvant effect of IgG molecule fragments present in the serum of partially hepatectomized rabbits].
A F (ab)2 -like fragment of IgG isolated from the serum of partially hepatectomized rabbits was capable of enhanceing an immune response in rabbits xenogenous erythrocytes. This enhancing effect was revealed by an increase of both the number of antibody-forming cells in the spleen and the titres of 19S and 7S hemagglutinins.


Morphological Responses and Gene Expression of Grain Amaranth (Amaranthus spp.) Growing under Cd.
Phytoremediation efficiency depends on the ability of plants to accumulate, translocate and resist high levels of metals without symptoms of toxicity. This study was conducted to evaluate the potential of grain amaranth for remediation of soils contaminated with Cd. Three grain amaranth varieties, "Pribina" (A. cruentus), "Zobor" (A. hypochondriacus x A. hybridus) and Plainsman (A. hypochondriacus x A. hybridus) were tested under different level of Cd (0, 5, 10 and 15 mg/L) in a hydroponic experimental treatment. All could be classified as Cd excluders or Cd-hypertolerant varieties able to grow and accumulate significant amounts of Cd from the hydroponic solution, preferentially in the roots. Under the highest level of Cd exposure, qRT-PCR expression analysis of five stress-related genes was examined in above- and below-ground biomass. The results show that the Cd concentration significantly increased the mRNA level of chitinase 5 (Chit 5) in amaranth roots as the primary site of metal stress. The involvement of phytochelatin synthase (PCS1) in Cd detoxification is suggested. Based on our findings, we can conclude that variety "Pribina" is the most Cd-tolerant among three tested and can be expected to be used in the phytomanagement of Cd loaded soils as an effective phytostabiliser.


Experimental allergic encephalomyelitis induced by basic protein with synthetic adjuvant in comparison with Freund's complete adjuvant. Role of antibodies in correlation with the clinicopathological features.
Experimental allergic encephalomyelitis (EAE) was induced in guinea pigs with bovine myelin basic protein (BP) with adjuvant of either synthetic muramyl dipeptide (Mdp) or Mycobacterium tuberculosis (Tbc). The following results were obtained: (1) The body temperature of the animals was studied serially after sensitization and its elevation was shown to be an early sign of EAE. (2) Several animals developed the clinical and histological signs of hyperacute EAE. (3) An optimal combined dosage of BP and adjuvant was found for induction of clinical EAE and for the the production of complement fixing (CF) antibodies. (4) Little passive hemagglutinating (PH) antibody was produced by single immunization. These results displayed no essential difference in EAE induced by either adjuvant. (5) Detectable PH antibodies developed later in addition to CF antibodies in a few animals immunized with Tbc adjuvant. These animals were skin-tested to BP, and had recovered from body weight loss or limb weakness. The results suggest that humoral antibodies play a role in modifying the disease process, even if they are not essential in production of EAE.


Isolation, identification and antimicrobial activity of propolis-associated fungi.
Propolis is a natural product widely known for its medicinal properties. In this work, fungi present on propolis samples were isolated, identified and tested for the production of antimicrobial metabolites. Twenty-two fungal isolates were obtained, some of which were identified as Alternaria alternata, Aspergillus flavus, Bipolaris hawaiiensis, Fusarium merismoides, Lasiodiplodia theobromae, Penicillium citrinum, Penicillium crustosum, Penicillium janthinellum, Penicillium purpurogenum, Pestalotiopsis palustris, Tetracoccosporium paxianum and Trichoderma koningii. These fungi were grown in liquid media to obtain crude extracts that were evaluated for their antibiotic activity against pathogenic bacteria, yeast and Cladosporium cladosporioides and A. flavus. The most active extract was obtained from L. theobromae (minimum inhibitory concentration = 64 μg/mL against Listeria monocitogenes). Some extracts showed to be more active than the positive control in the inhibition of Staphylococcus aureus and L. monocitogenes. Therefore, propolis is a promising source of fungi, which produces active agents against relevant food poisoning bacteria and crop-associated fungi.


[The effect of carbacholine and noradrenaline on intertissue connections during the reparative process].
Effects of carbacholine and noradrenaline on intertissue relations were studied in the experiment on rats experiencing healing of their wounds of the skin. Choline- and adrenergic stimulations were shown to both quantitatively and qualitatively change the course of posttraumatic regeneration of the skin, which developments are accompanied by change of intertissue interrelationships between the epidermis and connective tissue.


Indicators Related to Marital Dissatisfaction.
This is a study on indicators related to marital dissatisfaction. The research was conducted by the psychology department of a reproductive health institution in Mexico City. The objective was to know the relation between marital satisfaction/dissatisfaction and gender roles, self-esteem, the types of coping strategies and the types of violence perceived from the partner. It was a nonexperimental, retrospective, cross-sectional study of two samples-one of women and one of men-classified by marital satisfaction or dissatisfaction. The nonprobability quota sampling included 208 participants: 104 women and 104 men. Comparisons, correlations and a discriminant analysis were made to identify the most significant variables. Women with marital dissatisfaction perceived blackmail, psychological violence and humiliation/devaluation from their partner; they preferably adopt a submissive gender role and use escape/avoidance as a coping strategy, and so do the men with marital dissatisfaction, who also perceived blackmail, control and psychological violence from their partner; they have low self-esteem, and they preferably adopt a submissive gender role. Isolating factors will allow for more specificity in terms of psychological care at health institutions as well as avoiding gender biases and preventing an increase of violence in couples.


Comparison between Single Versus Twice Application of Topical 85% Trichloroacetic Acid in the Treatment of Cervical Intraepithelial Neoplasia; A Randomized Clinical Trial on Efficacy and Tolerability.
To compare the efficacy and safety of up to two-time administration of 85% TCA, as a promising alternative therapy to conservative and surgical management of grade one to three CINs. In this two-armed randomized clinical trial, a total of 53 patients with biopsy-proven CIN lesions were allocated to two groups of TCA treatment. The first group (n=26) received a single dose of local therapy with 85% TCA while the second group (n=27) was treated on two separate occasions with a two-week interval. Two participants (one in each group) were lost to follow-up. At the two-month follow-up after TCA application, a colposcopy-guided biopsy was performed for all patients and the pathological specimens were studied by a single experienced pathologist to determine the post-intervention grading of CIN. Two groups were comparable in terms of age and base-line lesion grading, as CIN 1 lesions comprised the majority of cases (54%), followed by CIN 2(37%). While our sample was a poor representative of CIN3 lesions (7%), no significant difference was noticed between the single and twice TCA treated groups with a response rate of 52% and 54% respectively (either complete remission to normal histology or regression to any low-grade lesion). Either separate analysis (with respect to the base-line grading within each treatment group) or combined analysis (regardless of CIN sub-group) could not generate any statistical significance. The second dose of TCA did not increase the frequency of reported adverse events. The second dose of topical 85% TCA does not seem to increase the CIN response rate more so than its single dose. However, further controlled clinical trials with larger samples are warranted to verify current findings. The use of TCA was not limited by any major side effect, therefore, the potential to achieve an increased efficacy with more frequent TCA applications is appealing.


The effect of feedback delay on perceptual category learning and item memory: Further limits of multiple systems.
Delayed feedback during categorization training has been hypothesized to differentially affect 2 systems that underlie learning for rule-based (RB) or information-integration (II) structures. We tested an alternative possibility: that II learning requires more precise item representations than RB learning, and so is harmed more by a delay interval filled with a confusable mask. Experiments 1 and 2 examined the effect of feedback delay on memory for RB and II exemplars, both without and with concurrent categorization training. Without the training, II items were indeed more difficult to recognize than RB items, but there was no detectable effect of delay on item memory. In contrast, with concurrent categorization training, there were effects of both category structure and delayed feedback on item memory, which were related to corresponding changes in category learning. However, we did not observe the critical selective impact of delay on II classification performance that has been shown previously. Our own results were also confirmed in a follow-up study (Experiment 3) involving only categorization training. The selective influence of feedback delay on II learning appears to be contingent on the relative size of subgroups of high-performing participants, and in fact does not support that RB and II category learning are qualitatively different. We conclude that a key part of successfully solving perceptual categorization problems is developing more precise item representations, which can be impaired by delayed feedback during training. More important, the evidence for multiple systems of category learning is even weaker than previously proposed. (PsycINFO Database Record


Regulatory mechanisms and cell membrane properties of Candida glycerinogenes differ under 2-phenylethanol addition or fermentation conditions.
The biosynthesis of 2-phenylethanol (2-PE) at high yields and titers is often limited by its toxicity. In this study, we describe the molecular mechanisms of 2-PE tolerance in the multi-stress tolerant industrial yeast, Candida glycerinogenes. They were different under 2-PE addition or fermentation conditions. After extracellular addition of 2-PE, C. glycerinogenes cells became rounder and bigger, which reduced specific surface area. However, during 2-PE fermentation C. glycerinogenes cells were smaller, which increased specific surface area. Other differences in the tolerance mechanisms were studied by analyzing the composition and molecular parameters of the cell membrane. Extracellular 2-PE stress resulted in down-regulation of transcriptional expression of unsaturated fatty acid synthesis genes. This raised the proportion of saturated fatty acids in the cell membrane, which increased rigidity of the cell membrane and reduced 2-PE entry to the cell. However, intracellular 2-PE stress resulted in up-regulation of transcriptional expression of unsaturated fatty acid synthesis genes, and increased the proportion of unsaturated fatty acids in the cell membrane; this in turn enhanced flexibility of the cell membrane which accelerated efflux of 2-PE. These contrasting mechanisms are mediated by transcriptional factors Hog1 and Swi5. Under 2-PE addition, C. glycerinogenes activated Hog1 and repressed Swi5 to upregulate erg5 and erg4 expression, which increased cell membrane rigidity and resisted 2-PE import. During 2-PE fermentation, C. glycerinogenes activated Hog1 and repressed Swi5 to upregulate 2-PE transporter proteins cdr1 and Acyl-CoA desaturase 1 ole1 to increase 2-PE export, thus reducing 2-PE intracellular toxicity. The results provide new insights into 2-PE tolerance mechanisms at the cell membrane level and suggest a novel strategy to improve 2-PE production by engineering anti-stress genes.


Central Sensitization and Perceived Indoor Climate among Workers with Chronic Upper-Limb Pain: Cross-Sectional Study.
Monitoring of indoor climate is an essential part of occupational health and safety. While questionnaires are commonly used for surveillance, not all workers may perceive an identical indoor climate similarly. The aim of this study was to evaluate perceived indoor climate among workers with chronic pain compared with pain-free colleagues and to determine the influence of central sensitization on this perception. Eighty-two male slaughterhouse workers, 49 with upper-limb chronic pain and 33 pain-free controls, replied to a questionnaire with 13 items of indoor climate complaints. Pressure pain threshold (PPT) was measured in muscles of the arm, shoulder, and lower leg. Cross-sectional associations were determined using general linear models controlled for age, smoking, and job position. The number of indoor climate complaints was twice as high among workers with chronic pain compared with pain-free controls (1.8 [95% CI: 1.3-2.3] versus 0.9 [0.4-1.5], resp.). PPT of the nonpainful leg muscle was negatively associated with the number of complaints. Workers with chronic pain reported more indoor climate complaints than pain-free controls despite similar actual indoor climate. Previous studies that did not account for musculoskeletal pain in questionnaire assessment of indoor climate may be biased. Central sensitization likely explains the present findings.


Diet Reversal and Immune Modulation Show Key Role for Liver and Adipose Tissue T Cells in Murine Nonalcoholic Steatohepatitis.
Nonalcoholic steatohepatitis (NASH) is a multisystem condition, implicating liver and adipose tissue. Although the general involvement of the innate and adaptive immune system has been established, we aimed to define the exact role of the functionally diverse T-cell subsets in NASH pathogenesis through diet reversal and immunologic modulation. Multiple experimental set-ups were used in 8-week-old C57BL/6J mice, including prolonged high-fat high-fructose diet (HFHFD) feeding, diet reversal from HFHFD to control diet, and administration of anti-CD8a and anti-interleukin 17A antibodies. Plasma alanine aminotransferase, glucose, and lipid levels were determined. Liver and adipose tissue were assessed histologically. Cytotoxic T (Tc), regulatory T, T helper (Th) 1, and Th17 cells were characterized in liver and visceral adipose tissue (VAT) via flow cytometry and RNA analysis. HFHFD feeding induced the metabolic syndrome and NASH, which coincided with an increase in hepatic Th17, VAT Tc, and VAT Th17 cells, and a decrease in VAT regulatory T cells. Although diet reversal induced a phenotypical metabolic and hepatic normalization, the observed T-cell disruptions persisted. Treatment with anti-CD8a antibodies decreased Tc cell numbers in all investigated tissues and induced a biochemical and histologic attenuation of the HFHFD-induced NASH. Conversely, anti-interleukin 17A antibodies decreased hepatic inflammation without affecting other features of NASH or the metabolic syndrome. HFHFD feeding induces important immune disruptions in multiple hepatic and VAT T-cell subsets, refractory to diet reversal. In particular, VAT Tc cells are critically involved in NASH pathogenesis, linking adipose tissue inflammation to liver disease.


From a Slave to a Surgeon: David Kearney McDonogh, the First Black Otolaryngologist.
David McDonogh, born into chattel slavery in Louisiana in the early 1800s, accomplished the unfathomable by becoming the first Black otolaryngologist in the United States of America. With tireless determination and profound intellect, Dr McDonogh surmounted immeasurable adversity along his improbable journey to freedom and success as an eye, ear, nose, and throat doctor in New York. His doctorate in medicine was posthumously awarded to his great-great-granddaughter in 2018 by the Columbia University Vagelos College of Physicians and Surgeons. In this History of Otolaryngology piece, we share his extraordinary story.


Role of Hypovitaminosis D in the Pathogenesis of Obesity-Induced Insulin Resistance.
Obesity and type 2 diabetes have both rapidly increased during the last decades and are continuing to increase at an alarming rate worldwide. Obesity and impaired glucose homeostasis are closely related, and during the last decades of investigation about vitamin D, several clinical and epidemiological studies documented an inverse correlation between circulating vitamin D levels, central adiposity and the development of insulin resistance and diabetes. The insufficient sun exposure and outdoor activities of obese individuals, the storage of vitamin D in adipose tissue, because of its lipophilic properties, and the vitamin D-mediated modulation of adipogenesis, insulin secretion, insulin sensitivity and the immune system, are the main reasons for the close relationship between obesity, glucose homeostasis and hypovitaminosis D. Then objective of this review is to explore the pathophysiological mechanism(s) by which vitamin D modulates glycemic control and insulin sensitivity in obese individuals.


[Limb salvage in diabetic foot syndrome with pedal bypass using the in-situ technique].
Treatment of the ischemic diabetic foot syndrome still represents a medical and economic challenge. Contrary to the aims of the Saint Vincent declaration a dramatic reduction of major amputations in Germany was not noted, although in the diabetic patients the predominant type of tibial artery occlusion allows construction of pedal bypasses for limb salvage. In patients with ischemic diabetic foot syndrome following angiographic evaluation of the ischemic limb, the indication for surgical revascularisation of patent pedal arteries was established. The in-situ technique was preferred in the presence of a suitable ipsilateral greater saphenous vein whenever possible. Revascularisation was followed by treatment of foot ulcerations or, if necessary, minor amputations. Patients were followed by clinical examination and duplex scan investigation of the bypass in regular intervals. From 01/89 to 12/01 in 79 patients (59 men and 20 women) with non healing ulcerations or established gangrene from a total of 175 pedal bypasses 84 pedal bypass operations in 84 limbs were performed using the in-situ technique. All patients were diabetic and in addition 13.9% were dependent on hemodialysis for end stage renal disease. 59.5% of the bypasses originated from the popliteal artery (distal origin bypass). The dorsalis pedis artery was chosen for the distal anastomosis in 83% and the posterior tibial artery in 17%. Two patients (2.4%) died postoperatively from cardiac events. Early bypass occlusion occurred in 8.4% resulting in a major amputation rate of 6%. After 60 months primary, primary assisted and secondary patency was 67.7%, 71.5% and 75.3% respectively with a limb salvage rate of 78%. Pedal bypass using the in-situ technique provides excellent long term limb salvage rates in a disease with a generally unjustified bad prognosis with respect to limb salvage.


Association of the total cholesterol content of erythrocyte membranes with the severity of disease in stable coronary artery disease.
Increasing evidence suggests that erythrocytes may participate in atherogenesis. We sought to investigate whether the total cholesterol content of erythrocyte membranes (CEM) is significantly different in patients with stable coronary artery disease (CAD) compared to patients with nonsignificant coronary stenosis and determine the correlation between CEM and the severity of coronary stenosis. Methods. The population included 144 patients, undergoing clinically indicated coronary angiography. The severity of coronary stenosis was scored after coronary angiography and patients were divided into two groups; the S-stenosis group (CAD patients, n = 82) had a significant stenosis indicated by coronary angiography and the second group, N-stenosis (n = 62), had nonsignificant coronary stenosis. Lipid parameters were determined by routine laboratory methods. CEM was measured using an enzymatic assay, and protein content was assessed by the modified Lowry method. Results. The mean of CEM levels was higher (P < 0.001) in stable CAD patients (137.2 µg/mg of membrane protein) compared with N-stenosis patients (110.0 µg/mg of membrane protein). The coronary artery scores were correlated positively with CEM levels (r = 0.296, P < 0.001). Conclusion. CEM levels are positively associated with the severity of CAD, meaning that CEM might contribute to the development of CAD.


Predictors of uncontrolled hypertension in ambulatory patients.
Hypertension remains poorly controlled in the United States. Improvement of its management will require an understanding of the patient characteristics and treatment factors associated with uncontrolled hypertension. We studied antihypertensive medication use, comorbidity, and blood pressure measurements for 525 hypertensive patients in 3 different healthcare systems over a 1-year period. We concomitantly conducted comprehensive patient interviews covering demographic factors, knowledge of hypertension and its treatment, and medication side effects. Ordinal logistic regression was used to identify factors associated with poor blood pressure control. Mean age of the patients was 65+/-11 years. Mean systolic blood pressure (SBP) was 143+/-15 mm Hg; and mean diastolic blood pressure (DBP), 80+/-9 mm Hg. Only 39% (203/525) of patients had mean blood pressure <140/90 mm Hg during the study period; about half (257/525) had stage 1 hypertension (mean SBP 140 to 159 mm Hg and/or mean DBP 90 to 99 mm Hg), and 12% (65/525) had stage 2 or greater hypertension (SBP >160 mm Hgand/or DBP >100 mm Hg). Multivariate analysis revealed several independent predictors of poor control: older age, multi-drug regimens, lack of knowledge by the patient of their target SBP, and a report of antihypertensive drug side effects. Patients with angina had a higher likelihood of adequate blood pressure control. Fewer than 40% of the treated patients studied had a mean blood pressure </=140/90 mm Hg, and specific patient-related factors appear to predict poor control. Some of these may be amenable to modification. Further identification of patients at risk of poor control can lead to targeted interventions to improve management.


Pathogenesis of cardiovascular disorders in streptozotocin-induced diabetes in rat. I. Cardiovascular, renal and morphologic changes in different stages of diabetes.
Some cardiovascular (heart rate and mean arterial pressure), and renal (glomerular filtration rate-GFR; renal plasma flow-RPF; filtration fraction-FF; blood urea nitrogen-BUN and albuminuria) parameters, coupled with morphologic examination, was undertaken in early (2 months) and late (6 months) stage of streptozotocin-induced diabetes mellitus in rats. The results showed a temporally (early) bradycardia and gradually increase of blood pressure with morphologic changes typical for diabetic cardiopathy. The increased GFR (by 92%), associated with significantly decreased RPF (by 37%), increased FF (by 133%), increased kidney weight/body weight ratio (by 88%), increased BUN (by 52%) and distinct albuminuria (13.53 +/- 2.08 mg/24 h/100 g b. w.), together with typical morphologic changes, suggested the development of diabetic nephropathy which was progressive with the duration of the disease.


[Brazilian Protocol for Sexually Transmitted Infections 2020: infections that cause genital ulcers].
Infections that cause genital ulcers are one of the themes comprising the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. The Protocol and Guidelines have been developed based on scientific evidence and validated in discussions with specialists. This article addresses clinical genital ulcer syndrome caused by sexually transmitted infections, and its most common etiological agents: Treponema pallidum (syphilis), herpes simplex virus-2 (genital herpes) and herpes simplex virus-1 (perioral herpes), Haemophilus ducreyi (chancroid), Chlamydia trachomatis serotypes L1, L2 and L3 (venereal lymphogranuloma), and Klebsiella granulomatis (donovanosis). Epidemiological and clinical aspects of these infections are presented, as well as guidelines for their diagnosis and treatment, in addition to strategies for surveillance, prevention and control actions, with the purpose of supporting health managers and professionals in the qualification of care.


Occurrence of Plasmid- and Chromosome-Carried mcr-1 in Waterborne Enterobacteriaceae in China.
The aim of this study was to investigate the prevalence of the polymyxin resistance gene mcr-1 in Enterobacteriaceae from environmental water sources in Hangzhou, China. Colistin-resistant bacteria were isolated from environmental water samples using an enrichment broth culture method, were screened for mcr-1, and then were analyzed for the location and transferability of mcr-1 Isolates positive for mcr-1 were further examined to determine their susceptibility profiles and were screened for the presence of additional resistance genes. Twenty-three mcr-1-positive isolates (16 Escherichia coli, two Citrobacter freundii, two Klebsiella oxytoca, two Citrobacter braakii, and one Enterobacter cloacae) were isolated from 7/9 sampling locations; of those, eight mcr-1-positive isolates also contained β-lactamase-resistance genes, eight contained qnrS, and 10 contained oqx No mcr-2-positive isolates were identified. The majority of isolates demonstrated a low to moderate level of colistin resistance. Transconjugation was successfully conducted from 14 of the 23 mcr-1-positive isolates, and mcr-1 was identified on plasmids ranging from 60 to 220 kb in these isolates. Conjugation and hybridization experiments revealed that mcr-1 was chromosome-borne in only three isolates. Pulsed-field gel electrophoresis showed that the majority of E. coli isolates belonged to different clonal lineages. Multilocus sequence typing analysis revealed that sequence type 10 (ST10) was the most prevalent, followed by ST181 and ST206. This study demonstrates the utility of enrichment broth culture for identifying environmental mcr-1-positive isolates. Furthermore, it highlights the importance of responsible agriculture and clinical use of polymyxins to prevent further widespread dissemination of polymyxin-resistant pathogens.


[Cholesterol crystals and biliary lithiasis. Importance of the study of bile collected by duodenal intubation].
Cholesterol crystallization in a necessary step in the formation of cholesterol gallstones. Our purpose was to study the relationship between the presence of biliary cholesterol crystals and radiolucent gallstones. Bile was obtained by duodenal intubation from 60 subjects free of hepatic disease: 40 patients had radiolucent gallstones and in the remaining 20 subjects no gallstones could be found either by oral cholecystography or by ultrasound examination. In each patient a bile sample was used to search for cholesterol crystals; in another sample, biliary cholesterol, phospholipids and bile acids were measured to calculate the lithogenic index. Among the 44 subjects with lithogenic bile, 34 had radiolucent gallstones. Twenty-two out of the 60 patients had both cholesterol crystals and radiolucent gallstones; 21 subjects out of the 22 had lithogenic bile. In patients with frequent biliary colic or subacute pancreatitis without visible gallstones, finding cholesterol crystals in bile might suggest medical or surgical specific treatment.


Myosin Va mutation in rats is an animal model for the human hereditary neurological disease, Griscelli syndrome type 1.
A spontaneous neurological mutation, dilute-opisthotonus (dop), was discovered in our breeding colony of Wistar rats. We found that the mutation affected the gene encoding Myosin Va (MyoVA), an actin-based molecular motor. Analysis of the myosin Va (Myo5a) gene of the dop genome showed the presence of a complex rearrangement consisting of a 306-bp inversion associated with 217-bp and 17-bp deletions. A 141-bp exon is skipped in the dop transcript, producing a dop cDNA with a 141 in-frame deletion in the sequences encoding the head region. Expression of the MyoVA protein is severely impaired in the brains of dop homozygous rats, suggesting they have a null mutation for Myo5a. In a morphological analysis of the cerebella of dop rats, we found an absence of smooth endoplasmic reticulum (SER) and of inositol 1,4,5-triphosphate (IP3) receptors in the dendritic spines of Purkinje cells (PC). The SER acts as an intracellular Ca(2+) store and IP3-mediated Ca(2+) signaling in dendritic spines plays a critical role in synaptic regulation. We therefore measured synaptic transmission and long-term depression (LTD), a form of synaptic plasticity underlying cerebellar motor learning, at PC synapses in the cerebella of dop rats. We found that synaptic transmission at the PC synapses is largely normal, whereas the LTD is deficient due to a decrease in IP3-mediated Ca(2+) release from the SER in the PC spines of the dop cerebella. These findings may account for the ataxic movements and clonic convulsions displayed by dop rats. They also contribute to our understanding of the neurological disease mechanisms of the human hereditary disease Griscelli syndrome type 1, which is caused by mutation of the Myo5a gene.


Molecular cloning of sheep and goat ferredoxin reductase messenger ribonucleic acids, and identification of an alternatively spliced form of sheep ferredoxin reductase.
Complementary DNA clones of mRNAs for sheep and goat NADPH-ferredoxin reductases (ferredoxin NADP+ oxidoreductase, EC 22.214.171.124) were isolated by the reverse transcriptase polymerase chain reaction method, and the complete nucleotide sequences of the coding and 3'-flanking regions of these cDNA clones were determined. Comparative analysis using the deduced amino acid sequences of NADPH-ferredoxin reductases clarified the interspecific conservation of the ferredoxin-binding and flavin adenine dinucleotide (FAD)-binding regions, confirming the results reported previously. During this study, we happened to identify an alternatively spliced mRNA that completely lacks exon 3, just adjacent to the FAD-binding region of the sheep NADPH-ferredoxin reductase cDNA clone. In the screening of other alternatively spliced mRNAs of NADPH-ferredoxin reductases derived from several steroidogenic organs, such as adrenocortices, testes, and ovaries of sheep and goats, only one kind of alternatively spliced mRNA as described above was detected in sheep adrenocortices. Then, we constructed Escherichia coli expression systems for these two forms of mRNA and analyzed their enzymatic properties. We found that the ability of the alternatively spliced NADPH-ferredoxin reductase protein to transfer electrons to ferredoxin is completely abolished because FAD binding is inhibited.


Ruminant-specific multiple duplication events of PRDM9 before speciation.
Understanding the genetic and evolutionary mechanisms of speciation genes in sexually reproducing organisms would provide important insights into mammalian reproduction and fitness. PRDM9, a widely known speciation gene, has recently gained attention for its important role in meiotic recombination and hybrid incompatibility. Despite the fact that PRDM9 is a key regulator of recombination and plays a dominant role in hybrid incompatibility, little is known about the underlying genetic and evolutionary mechanisms that generated multiple copies of PRDM9 in many metazoan lineages. The present study reports (1) evidence of ruminant-specific multiple gene duplication events, which likely have had occurred after the ancestral ruminant population diverged from its most recent common ancestor and before the ruminant speciation events, (2) presence of three copies of PRDM9, one copy (lineages I) in chromosome 1 (chr1) and two copies (lineages II & III) in chromosome X (chrX), thus indicating the possibility of ancient inter- and intra-chromosomal unequal crossing over and gene conversion events, (3) while lineages I and II are characterized by the presence of variable tandemly repeated C2H2 zinc finger (ZF) arrays, lineage III lost these arrays, and (4) C2H2 ZFs of lineages I and II, particularly the amino acid residues located at positions -1, 3, and 6 have evolved under strong positive selection. Our results demonstrated two gene duplication events of PRDM9 in ruminants: an inter-chromosomal duplication that occurred between chr1 and chrX, and an intra-chromosomal X-linked duplication, which resulted in two additional copies of PRDM9 in ruminants. The observation of such duplication between chrX and chr1 is rare and may possibly have happened due to unequal crossing-over millions of years ago when sex chromosomes were independently derived from a pair of ancestral autosomes. Two copies (lineages I & II) are characterized by the presence of variable sized tandem-repeated C2H2 ZFs and evolved under strong positive selection and concerted evolution, supporting the notion of well-established Red Queen hypothesis. Collectively, gene duplication, concerted evolution, and positive selection are the likely driving forces for the expansion of ruminant PRDM9 sub-family.


Adherence of randomised controlled trials using artificial intelligence in ophthalmology to CONSORT-AI guidelines: a systematic review and critical appraisal.
Many efforts have been made to explore the potential of deep learning and artificial intelligence (AI) in disciplines such as medicine, including ophthalmology. This systematic review aims to evaluate the reporting quality of randomised controlled trials (RCTs) that evaluate AI technologies applied to ophthalmology. A comprehensive search of three relevant databases (EMBASE, Medline, Cochrane) from 1 January 2010 to 5 February 2022 was conducted. The reporting quality of these papers was scored using the Consolidated Standards of Reporting Trials-Artificial Intelligence (CONSORT-AI) checklist and further risk of bias was assessed using the RoB-2 tool. The initial search yielded 2973 citations from which 5 articles satisfied the inclusion/exclusion criteria. These articles featured AI technologies applied to diabetic retinopathy screening, ophthalmologic education, fungal keratitis detection and paediatric cataract diagnosis. None of the articles reported all items in the CONSORT-AI checklist. The overall mean CONSORT-AI score of the included RCTs was 53% (range 37%-78%). The individual scores of the articles were 37% (19/51), 39% (20), 49% (25), 61% (31) and 78% (40). All articles were scored as being moderate risk, or 'some concerns present', regarding potential risk of bias according to the RoB-2 tool. A small number of RCTs have been published to date on the applications of AI in ophthalmology and vision science. Adherence to the 2020 CONSORT-AI reporting guidelines is suboptimal with notable reporting items often missed. Greater adherence will help facilitate reproducibility of AI research which can be a stimulus for more AI-based RCTs and clinical applications in ophthalmology.


Enol ethers as carbonyl surrogates in a modification of the Povarov synthesis of 3-aryl quinolines and their anti-Toxoplasma activity.
A novel method for the preparation of 2-carboxyl-3-aryl quinoline derivatives from anilines, ethyl glyoxalate and enol ethers as phenylacetaldehyde surrogates is reported. The three-component coupling reaction occurs rapidly under mild conditions in dichloromethane catalysed by TFA. The method allows a more direct access to 3-aryl quinolines, sidestepping issues encountered with phenylacetaldehyde derivatives. This chemistry was used to prepare quinolines with 3-diarylether functionality that showed low micromolar efficacy (IC50 range: 5-26 μM) against in vitro Toxoplasma gondii coupled with little or no cytotoxicity (TD50≥ 320 μM) towards the host cells.


Photofrin uptake in the tumor and normal tissues of patients receiving intraperitoneal photodynamic therapy.
A phase II trial of Photofrin-mediated i.p. photodynamic therapy shown in a previous report limited efficacy and significant acute, but not chronic, toxicity. A secondary aim of this trial and the subject of this report is to determine Photofrin uptake in tumor and normal tissues. Patients received Photofrin, 2.5 mg/kg, i.v., 48 hours before debulking surgery. Photofrin uptake was measured by spectroflurometric analysis of drug extracted from tumor and normal tissues removed at surgery. Differences in drug uptake among these tissues were statistically considered using mixed-effects models. Photofrin concentration was measured in 301 samples collected from 58 of 100 patients enrolled on the trial. In normal tissues, drug uptake significantly (P<0.0001) differed as a function of seven different tissue types. In the toxicity-limiting tissue of intestine, the model-based mean (SE) Photofrin level was 2.70 ng/mg (0.32 ng/mg) and 3.42 ng/mg (0.24 ng/mg) in full-thickness large and small intestine, respectively. In tumors, drug uptake significantly (P=0.0015) differed as a function of patient cohort: model-based mean Photofrin level was 3.32 to 5.31 ng/mg among patients with ovarian, gastric, or small bowel cancer; 2.09 to 2.45 ng/mg among patients with sarcoma and appendiceal or colon cancer; and 0.93 ng/mg in patients with pseudomyxoma. Ovarian, gastric, and small bowel cancers showed significantly higher Photofrin uptake than full-thickness large and/or small intestine. However, the ratio of mean drug level in tumor versus intestine was modest (<or=2.31). Some selectivity is found in Photofrin uptake between tumor and normal tissues of the peritoneal cavity, but absolute differences in drug uptake relative to toxicity-limiting normal tissues (intestine) are small. This narrow differential in drug selectivity likely contributes to a narrow window in therapeutic application, which has been previously reported.


[Intrinsic and extrinsic connections of the postarcuate premotor area of the monkey].
Horseradish peroxidase conjugated with wheat germ agglutinine was injected in restricted parts of the postarcuate cortex in the macaque monkey. Anterograde and retrograde transport was found in the parietal and frontal lobes. In the parietal lobe two areas were marked: the antero-lateral part of area 7 and the superior bank of the sylvian fissure. In the frontal lobe the marked areas were the precentral motor cortex, the supplementary motor area and the gyrus cinguli. The intrinsic connections within the postarcuate cortex were rich and widespread. The hand representation was connected anterogradely and retrogradely with the mouth representation and anterogradely with the leg representation; the mouth representation was connected both ways with the hand representation but not with the leg area. The richness of intrinsic connections in the postarcuate cortex supports the suggestion that this area is involved in the organization of sequential motor acts.


Nutritional aspects in patients with non-alcoholic steatohepatitis (NASH).
Metabolic alterations are a common feature in patients affected by non-alcoholic steato-hepatitis (NASH). A strong correlation exists between overweight, in particular visceral fat accumulation, and prevalence of NASH, especially in men. Thus, diet-induced weight loss represents a fundamental tool in disease management of these patients. The aim of the present study was to evaluate body composition and nutrient utilisation in patients with NASH, comparing them with patients affected by chronic hepatitis related to hepatitis C virus (HCV) infection and with healthy subjects. Twenty male outpatients with NASH (age: 41 +/- 11 yr; BMI: 26.2 +/- 2.1 kg/m2) and 14 HCV male patients (age 44.6 +/- 13 yr; BMI: 24.8 +/- 2.8 kg/m2) were enrolled in the study. A group of 20 healthy male subjects (age: 39 +/- 10 yr; BMI: 23.3 +/- 1.1 kg/m2) were studied as controls. Body composition was assessed by anthropometry and dual-energy X-ray absorptiometry; resting metabolic rate and nutrient oxidation by indirect calorimetry. A 7-day food diary was collected. The main biochemical parameters were measured using standardised laboratory techniques. Body weight was higher in NASH patients with respect to HCV patients and control subjects (respectively 75.2 +/- 8.9 vs 68.5 +/- 9.4 and vs 67.0 +/- 8.0 kg; P < 0.01) and this was essentially due to fat mass increase. Fat-free mass reduction was found in HCV patients with respect to both NASH and control subjects. Patients with NASH had a significantly higher waist circumference (P < 0.01) and a lower resting metabolic rate (RMR) with respect to HCV and control subjects. Energy intake was significantly higher in NASH patients (P < 0.01) compared to the other two groups. NASH patients showed an increase in body weight, fat mass and visceral fat accumulation with respect to HCV and control subjects. The reduction in RMR, coupled with increase energy intake may explain the body composition alterations found in these patients.


Pathogenesis and management of emphysema in people with HIV.
Since early in the HIV epidemic, emphysema has been identified among people with HIV (PWH) and has been associated with increased mortality. Smoking cessation is key to risk reduction. Health maintenance for PWH and emphysema should ensure appropriate vaccination and lung cancer screening. Treatment should adhere to inhaler guidelines for the general population, but inhaled corticosteroid (ICS) should be used with caution. Frontiers in treatment include targeted therapeutics. Major knowledge gaps exist in the epidemiology of and optimal care for PWH and emphysema, particularly in low and middle-income countries (LMIC). Topics addressed include risk factors, pathogenesis, current treatment and prevention strategies, and frontiers in research. There are limited data on the epidemiology of emphysema in LMIC, where more than 90% of deaths from COPD occur and where the morbidity of HIV is most heavily concentrated. The population of PWH is aging, and age-related co-morbidities such as emphysema will only increase in salience. Over the next 5 years, the authors anticipate novel trials of targeted therapy for emphysema specific to PWH, and we anticipate a growing body of evidence to inform optimal clinical care for lung health among PWH in LMIC.


Histological experimental study on the effect of stem cell therapy on adriamycin induced chemobrain.
Negative consequences of chemotherapy on brain function were suggested and were addressed in animal models as the clinical phenomenon of chemobrain .It was postulated that adriamycin (ADR) induce changes in behaviour and in brain morphology. Human umbilical cord mesenchymal stem cells (HUCMSCs) could be induced to differentiate into neuron-like cells .The present study aimed at investigating the possible therapeutic effect of HUCMSC therapy on adriamycin induced chemobrain in rat. Twenty five female albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg ADR. The rats were sacrificed two and four weeks following confirmation of brain damage. In stem cell therapy group, rats were injected with HUCMSCs following confirmation of brain damage and sacrificed two and four weeks after therapy. Brain sections were exposed to histological, histochemical, immunohistochemical and morphometric studies. In ADR group, multiple shrunken neurons exhibiting dark nuclei and surrounded by vacuoles were seen .In response to SC therapy ,multiple normal pyramidal nerve cells were noted. The area of shrunken nerve cells exhibiting dark nuclei, Prussion blue and CD105 positive cells were significantly different in ADR group in comparison to SC therapy group. ADR induced progressive duration dependant cerebral degenerative changes. These changes were ameliorated following cord blood human mesenchymal stem cell therapy. A reciprocal relation was recorded between the extent of regeneration and the existence of undifferentiated mesenchymal stem cells.