ZM suture combined with early functional exercise can promote finger functional recovery in patients with finger flexor tendon rupture.
To investigate the efficacy of ZM suture combined with early functional exercise in repairing flexor tendons and its impact on finger function recovery in patients. A retrospective analysis was conducted on 60 patients who sought medical treatment at the Orthopedics Hospital of Xingtai City from August 2019 to August 2022. Among them, 29 patients treated with the modified Kessler suture technique were assigned to the control group, while 31 patients treated with ZM suture technique were assigned to the observation group. Both groups of patients underwent early functional exercise after surgery and were followed up regularly for 6 months. Finger function, grip strength, pinch strength at 6 months after operation, upper limb function before and after treatment, visual analog pain scale (VAS) at 1 and 2 weeks postoperatively, quality of life, and incidence of complications were compared between the two groups. The risk factors affecting the prognosis of patients were analyzed. At 6 months postoperatively, the observation group showed significantly better finger function, grip strength and grip strength ratio, and upper limb function compared to the control group (all P<0.05). The observation group had significantly lower VAS scores at 1 and 2 weeks postoperatively and a significantly lower incidence of complications compared to the control group, while their quality of life was significantly better than that of the control group (all P<0.05). The choice of treatment method is an independent risk factor affecting the prognosis of patients (P<0.05). The ZM suture technique combined with early functional exercise has significant efficacy in repairing flexor tendons, effectively promoting finger function recovery in patients. It is also associated with a high level of safety and warrants clinical application and promotion.


Recurrence of gigantic overhanging bleb post excision: a case report.
To report the case of an extremely large overhanging bleb, extending from superior fornix to limbus, in a 57-year-old poorly controlled diabetic, six years after trabeculectomy for an uncontrolled primary open angle glaucoma (POAG) with recurrence, months after complete excision. An overhanging bleb is defined as a filtering cicatrix which has been massaged downward over the cornea by eyelid action. It has been linked to anti-metabolite use during glaucoma filtering surgery. Despite being functional, these blebs result in patient discomfort ranging from foreign body sensation and lacrimation to dysphotopsia. A 57-year-old male presented with complaints of reduced vision, foreign body sensation, watering, and difficulty in eye closure in the left eye (OS) for past 6 months. He had undergone trabeculectomy with mitomycin C 6 years ago for advanced primary open-angle glaucoma with no follow-up beyond the initial one 4 weeks post-surgery. At presentation, he had a giant multi-loculated, cystic filtering bleb (15 mm x 8 mm x 4-5 mm), which was carefully excised. Amniotic membrane was used as an anti-fibrotic as well to cover the defect. Seven months after surgery, there was recurrence of this overhanging cystic bleb when it was again excised with debulking of the conjunctiva done and cryotherapy applied to its margins. Although multiloculated cystic overhanging blebs have been documented before, such a large (posterior extent till fornix), thick-walled multiloculated bleb with histopathological evidence of chronic inflammatory process has not been reported prior.


Gastrointestinal factors in nausea and vomiting of pregnancy.
The objective of this review is to outline gastrointestinal factors that may be relevant to nausea and vomiting of pregnancy. Gastric neuromuscular dysfunctions of the stomach include abnormalities in gastric myoelectrical activity, gastric tone, and contractility, all of which may result in gastroparesis. These abnormalities in gastric neural activity and smooth muscle function are associated with nausea and vomiting in nonpregnant patients. Gastric dysrhythmias are disturbances of gastric pacesetter potential patterns that are present during the nausea of motion sickness, drug-induced nausea, in patients with diabetic gastropathy, and women with nausea of pregnancy. In pregnant women with abdominal pain, nausea, and vomiting, standard gastrointestinal diseases such as gastroesophageal reflux, peptic ulcers, and cholecystitis must be considered. A diagnostic approach and therapeutic options for treating nausea and vomiting of pregnancy based on understanding of gastric neuromuscular dysfunction is outlined.


Effect of 3-D heat flow near edges in photothermal measurements.
Photothermal imaging scans often show large signal enhancement at sample edges. This effect can be attributed to 3-D heat flow within the sample. Geometric constraints which limit 3-D heat flow generally increase the sample surface temperature and the photothermal signal. The dependence of edge enhancement on sample thermal and physical dimensions is investigated for several systems containing one or more edges. Results suggest that geometrically restricted heat flow might explain the enhanced photothermal signal obtained for powders and other textured surfaces.


Dengue in the elderly: a review.
Changing dengue epidemiological trends have resulted in a shift in the disease burden to the adult population. Older adults suffer from poorer outcomes as compared to their younger counterparts, making clinical management of this sub-population particularly challenging. Areas covered: We present a review of the current literature on the changing epidemiology of dengue in the elderly, the atypical features of the clinical disease in this population with emphasis on severe disease presentations and challenges in the current management strategies. Expert commentary: Dengue in the elderly is an increasingly important yet greatly understudied area. There is an urgent need to refine the current diagnostic criteria to improve diagnosis, classification of disease severity and identify individuals in this population who are likely to progress to severe disease. Management strategies in this population would have to be adjusted to account for the increased number of co-morbidities. The role of the available dengue vaccines in this group is uncertain, and more studies into their safety and efficacy are critically needed.


Evidence for a multistep control in transposition of I factor in Drosophila melanogaster.
Drosophila melanogaster strains belong to one of two interactive categories, inducer (I) or reactive (R), with respect to the I-R system of hybrid dysgenesis. The dysgenic interaction results from the presence of several transposition-competent copies of a LINE-like element, the I factor, only in the genome of I strains. When a cross is performed between I males and R females, I factor transposes at high frequency in the germ line of F1 daughters, known as SF females. This transposition burst results in the sterility of SF females. I factor transposes by reverse transcription of a full-length transcript. Specific RT-PCR experiments were done to compare the amount of I factor transcript in samples corresponding to various transposition frequencies. The sensitivity of the method allowed the ready detection of the I factor RNA in every tissue and genetic background examined. Comparison of amplification signals suggests that I factor activity in ovaries is regulated at different levels. First, the amount of I factor RNA subjected to negative and positive regulation. Whereas the negative control, which limits transposition in nonpermissive contexts, may be exerted by an I factor encoded repressor function, the positive control is linked to reactivity level, a cellular state maternally inherited from R mothers. Additionally, negative regulation is also exerted downstream of I factor RNA. This differs notably from previous conclusions in which transcription was envisaged as the main level of regulation of the I factor transposition.


A three-month course of lamivudine therapy in HBeAg-positive hepatitis B patients with normal aminotransferase levels.
HBeAg-positive patients with normal ALT levels are unlikely to respond to current therapy. In addition, there is a high risk of hepatocellular carcinoma in HBeAg-positive patients in the natural course of HBV infection. For this purpose, we aimed to investigate the clinical efficacy and safety of a three-month course of lamivudine therapy in HBeAg-positive hepatitis B patients with normal aminotransferase levels for assessing a more practical and economical approach to these patients. Forty-six patients were prospectively randomized into two groups. Group A consisted of 13 patients treated with lamivudine 100 mg/day, for 12 weeks [7 males, mean age 23.30+/-5.82 years, median ALT of 27 IU/L (21-40), median HBV DNA of 4116 pg/ml (2885-6628)]. Group B consisted of 33 patients without treatment [18 males, mean age 24.75+/-6.92 years, median ALT of 30 IU/L (19-39), median HBV DNA of 4094 pg/ml (782-7387)]. Main outcome measure was sustained virologic response, which was defined as loss of HBV DNA in serum with HBeAg seroconversion at least 12 months thereafter. Follow-up lasted 12 months after the first dose. No significant effects were observed in the treated population in the reduction of HBV DNA to undetectable levels, in HBeAg/anti-HBe seroconversion, or in transaminase levels. At the end of follow-up, sustained virologic response was almost similar in the study as well as control group (7.6% vs. 3.0%, p=0.502). None of the 13 patients who received lamivudine therapy had HBeAg seroconversion during the study period. In addition, the suppression of serum HBV DNA was temporary; prolonged suppression could be achieved in only one patient in the follow-up period. The median levels of HBV DNA and ALT values between baseline and month 12 did not differ significantly between groups. All patients remained HBsAg positive and none developed anti-HBs. The therapy was well tolerated and post-therapy flare was not observed in any patient after stopping lamivudine therapy. A short course of lamivudine therapy resulted mostly in only temporarily depressed serum HBV DNA levels without significant change in viral clearance. Whether permanent suppression of HBV DNA can be achieved in this special population of HBsAg carriers by long-term treatment with lamivudine awaits further controlled trials. New and safe modalities of therapy are needed for the satisfactory treatment of these asymptomatic but viremic patients.


Stretching and bending fluctuations of short DNA molecules.
Recent measurements of the distribution of end-to-end distance in short DNA molecules infer cooperative stretching fluctuations. The assumptions underlying the analysis can be questioned if transient, thermally induced defects producing a localized decrease in bending stiffness are present in thermal equilibrium, such as regions in which DNA melts locally (bubbles), sustains large-angle bends (kinks), or can locally transform into an alternative (S-DNA) state. We study a generalized discrete worm-like chain model for DNA, capable of describing these experiments, showing that the model yields accurate fits to available experimental data. Our results indicate that DNA bending arising from such localized defects, rather than solely stretching, can be an equal contributor to end-to-end distance fluctuations for 35-bp DNA and contributes nontrivially to such fluctuations at all scales below the persistence length. The analysis suggests that such fluctuations should exhibit a scale-dependent cooperativity, specifically relevant in determining the behavior of short chains, but which saturates rapidly to a length-independent value for longer DNA, to ensure a consistent physical description of DNA across multiple scales. Our approach provides a minimal, yet accurate, coarse-grained description of DNA at the subpersistence length scales of current experimental interest.


Bacterial Production of a Pederin Analogue by a Free-Living Marine Alphaproteobacterium.
The polyketide pederin family are cytotoxic compounds isolated from insects, lichen, and marine sponges. During the past decade, different uncultivable bacteria symbionts have been proposed as the real producers of these compounds, such as those found in insects, lichen, and marine sponges, and their trans-AT polyketide synthase gene clusters have been identified. Herein we report the isolation and biological activities of a new analogue of the pederin family, compound 1, from the culture of a marine heterotrophic alphaproteobacterium, Labrenzia sp. PHM005. This is the first report of the production of a pederin-type compound by a free-living marine bacteria that could be cultured in the laboratory.


Laparoscopic indirect hernia repair: an evaluation of the ring closure technique.
The treatment of indirect inguinal hernias offers a wide variety of surgical methods to choose from. The author has chosen the procedure combining most of the advantages and the fewest disadvantages while at the same time being simple. It entails a simple closure using laparoscopic intraperitoneal intracorporeal suturing of the defect (the internal ring) with nonabsorbable material. Forty-eight hernias were treated by laparoscopic intracorporeal closure of the internal ring using nonabsorbable suture. No mesh was used. The mean age of the patients was 41.9 years with a mean duration of symptoms of 44.9 months. The mean operating time was 67 minutes per hernia, and the postoperative hospitalization was 1.9 days. The mean follow-up was 32.67 months. Only one hernia recurred (2%). None of the patients developed serious complications, and only 10 patients complained of port site discomfort. Our results indicate that the laparoscopic internal ring closure method is simple, safe, and effective in treating indirect inguinal hernias. In addition, it appears to be cost effective.


Absorption and first-pass metabolism of 14C-gamma-hydroxybutyric acid.
The recovery of radioactivity from plasma, urine and feces was determined in rats after administration of oral and intravenous doses (200 mg/kg) of 14C-labeled sodium gamma-hydroxybutyric acid. Very small portions of the radioactive dose were recovered in the urine (5.5%, oral; 7.1%, intravenous) and feces (1.5% oral; 0.6%, intravenous) collected between 0-48 hours after drug administration. Considerable levels of radioactivity were found in the plasma after oral dosing. The area under the plasma radioactivity time curve after an oral dose was found to be 65% of that observed after an equivalent intravenous dose. This value is much larger than the relative area value (8%) calculated on the basis of free gamma-hydroxybutyric acid. Results of this study strongly indicate that first-pass metabolism, rather than lack of absorption, is responsible for the apparently poor oral bioavailability of gamma-hydroxybutyric acid.


[The analgesic effect of red nucleus and strengthening effect thereof to the acupuncture analgesia].
The modulation of red nucleus (RN) to pain sense was researched with the latent period of radiant-heat tail flick of rats as standard of the pain threshold. The pain threshold of tail flick reflex was raised significantly by bilateral injection of glutamic acid into RN. Simultaneous injecting glutamic acid into RN and lidocaine into nucleus raphe magnus (NRM) could attenuate the raising effect of pain threshold of RN. This showed that the activated RN has analgesic effect and the NRM plays an important role in the descending inhibitory pathway of RN. The discharges of neurons in caudal part of nucleus spinalis tract nervi trigemini (cNST) evoked by stimulating nerve alveolaris inferior (nAI) with strong pulse were recorded with microelectrode. The nAI-evoked discharges might be inhibited by stimulating contralateral or ipsilateral RN. The RN inhibitory time course on nAI-evoked discharges were shortened after injecting lidocaine into NRM. This demonstrated that the inhibitory effect of RN on neurons in cNST is mediated by NRM. The electrical stimulation of acupoint "Jiache" could inhibit the pain-evoked discharges of neurons in cNST. The inhibitory time course of electrical acupuncture were prolonged by stimulating RN. This result revealed that the activated RN can strengthen the analgesic effect of acupuncture.


Immediate Treatment with Bicalutamide, 150 mg/d, Following Radiotherapy in Localized or Locally Advanced Prostate Cancer.
Previous studies and meta-analyses have made it clear that some subgroups of prostate cancer patients who have received radiotherapy should benefit from immediate adjuvant hormonal therapy. A cohort totaling 1370 patients who received radiotherapy for early nonmetastatic prostate cancer is currently enrolled in three ongoing, randomized, double-blind, placebo-controlled trials investigating the role of bicalutamide ('Casodex') 150 mg/d as adjuvant to standard care (the bicalutamide Early Prostate Cancer program). At preliminary analysis, conducted after a median follow-up of 3 years, adjuvant therapy with bicalutamide 150 mg/d significantly reduced the risk of objective progression by 37% compared with radiotherapy alone (HR 0.63, 95% CI, 0.46-0.85, P = .0024). Initial results demonstrate that bicalutamide 150 mg/d given as immediate adjuvant therapy following radiotherapy in men with early nonmetastatic prostate cancer has benefits over radiotherapy alone.


Use of antidepressants to treat depression in bipolar disorder.
For decades, clinicians and researchers did not distinguish between bipolar and unipolar depression. The safety and efficacy of antidepressants for the treatment of unipolar depression were studied, and the data were applied to the treatment of bipolar depression without validation. As evidence has accumulated that antidepressants may adversely affect the course of bipolar illness, more research has been focused on that problem. Current evidence suggests that although antidepressants are clearly effective in the acute treatment of type I and type II bipolar depression, they are also associated with a variety of adverse outcomes. They may induce a switch to mania or hypomania at a rate two or three times the spontaneous rate. Long-term use may destabilize the illness, leading to an increase in the number of both manic and depressed episodes; induce rapid cycling (at least four episodes a year); and increase the likelihood of a mixed state. Antidepressants should be used with caution in the treatment of bipolar depression.


Asunaprevir: An HCV Protease Inhibitor With Preferential Liver Distribution.
Asunaprevir is an inhibitor of the hepatitis C virus (HCV) NS3/4A protease, demonstrating efficacy in clinical studies in patients infected with HCV genotype 1 or 4, with either peginterferon/ribavirin or combinations of direct-acting antivirals. Because of preferential distribution of asunaprevir to the liver via organic anion-transporting polypeptide (OATP)-mediated transport, asunaprevir demonstrates high apparent oral clearance and very low plasma concentrations. Asunaprevir plasma concentrations are markedly increased by single-dose rifampin (an OATP inhibitor) and in subjects with moderate to severe hepatic impairment. In addition, modestly higher plasma concentrations of asunaprevir have been noted in subjects infected with HCV relative to healthy subjects and in Asian subjects relative to whites. At the marketed dose, infrequent hepatic transaminase abnormalities were poorly predicted by plasma concentrations. For a compound with these characteristics, hepatic concentrations may have provided an improved understanding of the in vivo pharmacokinetic and pharmacodynamic data to support decision making during development.


Theragnostic potentials of core/shell mesoporous silica nanostructures.
Theragnostics is considered as an emerging treatment strategy that integrates therapeutics and diagnostics thus allowing delivery of therapeutics and simultaneous monitoring of the progression of treatment. Among the different types of inorganic nanomaterials that are being used for nanomedicine, core shell mesoporous silica nanoparticles have emerged as promising multifunctional nanoplatform for theragnostic application. Research in the design of core/shell mesoporous silica nanoparticles is steadily diversifying owing to the various interesting properties of these nanomaterials that are advantageous for advanced biomedical applications. Core/shell mesoporous silica nanoparticles, have garnered substantial attention in recent years because of their exceptional properties including large surface area, low density, ease of functionalization, high loading capacity of drugs, control of the morphology, particle size, tunable hollow interior space and mesoporous shell and possibility of incorporating multifunctional interior core material. In the past decade researcher's demonstrated tremendous development in design of functionalized core/shell mesoporous silica nanoparticles with different inorganic functional nanomaterial incorporated into mesoporous nanosystem for simultaneous therapeutic and diagnostic (theragnostic) applications in cancer. In this review, we recapitulate the progress in commonly used synthetic strategies and theragnostic applications of core/shell mesoporous silica nanoparticles with special emphasis on therapeutic and diagnostic modalities. Finally, we discuss the challenges and some perspectives on the future research and development of theragnostic core/shell mesoporous silica nanoparticles.


Effects of Dried Blueberry Pomace and Pineapple Pomace on Growth Performance and Meat Quality of Broiler Chickens.
The purpose of this study was to investigate the effects of dried blueberry pomace (BP) and pineapple pomace (PP) on the growth performance and meat quality of broiler chickens. A total of 240 1-day-old Ross 308 broiler chickens were randomly divided into 3 groups, with 10 replicates per treatment group and 8 birds per replicate (4 males and 4 females). The three groups were the control (CON) group, the 3% BP group, and 3% PP group. The entire trial period lasted 42 days. The results show that the average daily feed intake, average daily gain, and feed-to-gain ratio of the BP group and the PP group were not significantly different from those in the CON group (p > 0.05). Adding BP to the diet significantly reduced the proportion of liver and giblets (p < 0.05). Adding PP to the diet significantly reduced the proportion of liver, while the proportion of gizzard significantly increased (p < 0.05). The pH24h and L* of breast muscles were significantly lower in the PP group than in the CON group (p < 0.05). The water-holding capacity of the leg muscles in the BP group and the PP group was significantly lower than that in the CON group (p < 0.05). The crude protein content of breast muscle and the ether extract content of leg muscle in the BP group were significantly lower than those in the CON group (p < 0.05). In conclusion, the addition of 3% BP and PP to broiler chickens' diets had no adverse effects on growth performance or meat quality.


Icodextrin with nitroprusside increases ultrafiltration and peritoneal transport during long CAPD dwells.
Addition of the nitric oxide (NO) donor nitroprusside to 1.36% glucose dialysate enlarges the effective peritoneal surface area during four-hour dwells. The theoretical positive effect on ultrafiltration is, however, counteracted by an increase in glucose absorption. The absorption of the glucose polymer icodextrin is much lower in comparison with glucose-based dialysis solutions, due to its high molecular weight. In the present study 7.5% icodextrin dialysis solution with and without the addition of 4.5 mg/liter nitroprusside was studied during eight-hour CAPD dwells. Two Standard Peritoneal permeability Analyses, adapted for eight-hour dwells, were performed in 10 stable CAPD patients. Nitrate and cGMP were measured as parameters of NO synthesis. The transcapillary ultrafiltration increased in a linear way with icodextrin (ICO) and was even higher after the addition of nitroprusside (NP): 666 (ICO) versus 834 (NP) ml/8 hr, P = 0.03. The effective lymphatic absorption rate was not different. The resulting net ultrafiltration increased with nitroprusside: 344 (ICO) versus 540 (NP) ml/8 hr, P < 0.01. The mass transfer area coefficient of urea increased 15% and that of creatinine 26% with nitroprusside, consistent with the expected enlargement of the vascular peritoneal surface area. The increase in protein clearances was more pronounced the larger the protein: beta 2-microglobulin 19%, albumin 47%, IgG 63% and alpha 2-macroglobulin 95%. Dialysate/plasma (D/P) ratios of nitrate were not higher than the expected values on the basis of its molecular weight (P < 0.001). They increased 19% with nitroprusside. Also, the D/P ratio cyclic guanosine monophosphate (cGMP) after four hours increased with nitroprusside (0.39, range 0.13 to 0.55 ICO, and 0.82, range 0.36 to 1.39 NP, P = 0.01). With nitroprusside the D/P ratio cGMP was higher than expected after four and eight hours (P < 0.001). This points to local generation of NO after addition of nitroprusside. The nitroprusside induced increase in the mass transfer area coefficients (MTAC) of creatinine and in the ultrafiltration caused an increase in the creatinine clearance from 4.2 ml/min to 5.0 ml/min during the eight-hour dwell. This means that nitroprusside adds 3 liters/week to the peritoneal clearance of creatinine. The adequacy of peritoneal dialysis can therefore be improved by the addition of nitroprusside to 7.5% icodextrin, used for the long exchange.


Effectiveness of Prehospital Epinephrine Administration in Improving Long-term Outcomes of Witnessed Out-of-hospital Cardiac Arrest Patients with Initial Non-shockable Rhythms.
We evaluated the association between prehospital epinephrine administration by emergency medical services (EMS) and the long-term outcomes of out-of-hospital cardiac arrest (OHCA) with initial pulseless electrical activity (PEA) or asystole. We conducted a controlled, propensity-matched, retrospective cohort study by using Japan's nationwide OHCA registry database. We studied 110,239 bystander-witnessed OHCA patients aged 15-94 years with initial non-shockable rhythms registered between January 2008 and December 2012. We created 1-1 matched pairs of patients with or without epinephrine by using sequential risk set matching based on time-dependent propensity scores to balance the patients' severity and characteristics. We compared overall and neurologically intact survival 1 month after OHCA between cases and controls using conditional logistic regression models by category of the initial rhythm. Propensity matching created 7,431 pairs in patients with PEA and 8,906 pairs in those with asystole. Epinephrine administration was associated with higher overall survival (4.49% vs. 2.96%; odds ratio [OR], 1.55; 95% confidence interval [CI], 1.30-1.85) but not with neurologically intact survival (0.98% vs. 0.78%; OR, 1.26; 95% CI, 0.89-1.78) in patients with PEA, and with higher overall survival (2.38% vs. 1.04%; OR, 2.34; 95% CI, 1.82-3.00) and neurologically intact survival (0.48% vs. 0.22%; OR, 2.28; 95% CI, 1.31-3.96) in those with asystole. Prehospital epinephrine administration by EMS is favorably associated with long-term neurological outcomes in patients with initial asystole and with long-term survival outcomes in those with PEA.


Preparation of water-free PEDOT dispersions in the presence of reactive polyisoprene stabilizers.
Poly(3,4-ethylenedioxythiophene) nanoparticles with narrow size distribution were prepared in organic dispersant media in the presence of both iron(III) dodecylbenzenesulfonate {Fe(DBS)3}-acting as both an oxidant and a stabilizer-and ω-functionalized polyisoprenes (ω-R-PI) as costabilizers. The effects of the solvent nature and concentration of Fe(DBS)3 on the size and morphology of the PEDOT particles were first studied in the absence of costabilizer. Second, the effects of the molar mass, concentration, and nature of the functional end group of the polyisoprene costabilizer were investigated. PEDOT nano-objects were characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), and conductivity measurements.


Preclinical discovery of duloxetine for the treatment of depression.
Affective disorders, including major depressive disorder (MDD), are among the most severely disabling mental disorders, and in many cases are associated with poor treatment outcomes. From the emergence of the monoamine hypothesis of depression, the first-line treatment for MDD had mainly acted by inhibiting monoamine reuptake, and thereby increasing these levels in the synaptic cleft. However, in recent years, several new antidepressant drugs have appeared, including duloxetine, a dual serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor recommended for the treatment of MDD. The article reviews and discusses the biochemical and functional profile of duloxetine splitting the review into acute and long-term treatment with this dual monoamine reuptake inhibitor. In addition, the authors summarize available preclinical behavioral research data, which have demonstrated among other effects, the antidepressant-like activity of duloxetine in several animal models. The authors focus on the most recent literature on synaptic neuroplasticity modulation of this antidepressant drug. Finally, the authors briefly mention other approved indications of duloxetine. Duloxetine inhibits 5-HT and NA reuptake, effectively desensitizes various autoreceptors and promotes neuroplasticity. Clinically, duloxetine is an effective antidepressant that is well tolerated and has significant efficacy in the treatment of MDD.


Conserved form and function of the germinal epithelium through 500 million years of vertebrate evolution.
The germinal epithelium, i.e., the site of germ cell production in males and females, has maintained a constant form and function throughout 500 million years of vertebrate evolution. The distinguishing characteristic of germinal epithelia among all vertebrates, males, and females, is the presence of germ cells among somatic epithelial cells. The somatic epithelial cells, Sertoli cells in males or follicle (granulosa) cells in females, encompass and isolate germ cells. Morphology of all vertebrate germinal epithelia conforms to the standard definition of an epithelium: epithelial cells are interconnected, border a body surface or lumen, are avascular and are supported by a basement membrane. Variation in morphology of gonads, which develop from the germinal epithelium, is correlated with the evolution of reproductive modes. In hagfishes, lampreys, and elasmobranchs, the germinal epithelia of males produce spermatocysts. A major rearrangement of testis morphology diagnoses osteichthyans: the spermatocysts are arranged in tubules or lobules. In protogynous (female to male) sex reversal in teleost fishes, female germinal epithelial cells (prefollicle cells) and oogonia transform into the first male somatic cells (Sertoli cells) and spermatogonia in the developing testis lobules. This common origin of cell types from the germinal epithelium in fishes with protogynous sex reversal supports the homology of Sertoli cells and follicle cells. Spermatogenesis in amphibians develops within spermatocysts in testis lobules. In amniotes vertebrates, the testis is composed of seminiferous tubules wherein spermatogenesis occurs radially. Emerging research indicates that some mammals do not have lifetime determinate fecundity. The fact emerged that germinal epithelia occur in the gonads of all vertebrates examined herein of both sexes and has the same form and function across all vertebrate taxa. Continued study of the form and function of the germinal epithelium in vertebrates will increasingly clarify our understanding of vertebrate reproduction. J. Morphol. 277:1014-1044, 2016. © 2016 Wiley Periodicals, Inc.


Pain: Systematic Review of Pharmacy Compounding of Pain Medication.
There are limited resources available for pharmacists and doctors to reference proper compounded formulas for pain medications. The systematic review discussed within this article provides the foundation for a searchable database, allowing users to find various compounded formulations. It also provides data about the safety and efficacy of the preparations. Compounding information about several drug classes was reviewed. Those drug classes included, but were not limited to, opioids, non-steroidal anti-inflammatory drugs, central nervous system agents, and anesthetics, with evidence that of the various drugs that could be compounded for pain, anesthetics, non-steroidal anti-inflammatory drugs, and opioids ranked highest within the articles researched.


Metal mixture inhalation (Cd-Pb) and its effects on the bronchiolar epithelium. An ultrastructural approach.
The current study explores the effects of the inhalation of lead (Pb), Cd and its mixture (Pb-Cd) in a mice model, analysing metal concentrations in the lung, and the morphological modifications in the bronchiolar epithelium identified by scanning electron microscopy after eight weeks of inhalation. Our results indicate that metal concentrations in lung were higher compared to controls; however, Pb concentrations drastically decrease in the mixture. This reduction was also observed in the inhalation chamber. The main changes observed in the bronchiole were mostly in the mixture. The modifications were mainly given by Cd alone and in the mixture, with a decreased number of nonciliated bronchiolar cells and an increased number of bundles of dividing cells. The additive effect of Pb-Cd is suggested, as the extensive damage observed was more evident when mice were exposed to the mixture, and the results endured more research in the area of inhaled mixtures.


Production of immunologically active surface antigens of hepatitis B virus by Escherichia coli.
Several plasmids have been constructed which direct the synthesis of hepatitis B virus surface antigens in Escherichia coli either as the native polypeptide or fused to other plasmid encoded polypeptides. When injected into rabbits, extracts from bacteria carrying some of these plasmids induced the synthesis of antibodies to the antigens even though the extracts did not give satisfactory positive results in radioimmunoassay for them. Either the NH2-terminal segment or the COOH-terminal segment of the surface antigens alone was sufficient to elicit the immune response, but antibodies against the two segments showed different specificities. The results emphasize the value of an in vivo assay for the presence of antigens in crude cell extracts and illustrate the feasibility of this type of screening with laboratory animals.


Quantitative and qualitative analysis of the antifungal activity of allicin alone and in combination with antifungal drugs.
The antifungal activity of allicin and its synergistic effects with the antifungal agents flucytosine and amphotericin B (AmB) were investigated in Candida albicans (C. albicans). C. albicans was treated with different conditions of compounds alone and in combination (allicin, AmB, flucytosine, allicin + AmB, allicin + flucytosine, allicin + AmB + flucytosine). After a 24-hour treatment, cells were examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM) to measure morphological and biophysical properties associated with cell death. The clearing assay was conducted to confirm the effects of allicin. The viability of C. albicans treated by allicin alone or with one antifungal drug (AmB, flucytosine) in addition was more than 40% after a 24-hr treatment, but the viability of groups treated with combinations of more than two drugs was less than 32%. When the cells were treated with allicin alone or one type of drug, the morphology of the cells did not change noticeably, but when cells were treated with combinations of drugs, there were noticeable morphological changes. In particular, cells treated with allicin + AmB had significant membrane damage (burst or collapsed membranes). Classification of cells according to their cell death phase (CDP) allowed us to determine the relationship between cell viability and treatment conditions in detail. The adhesive force was decreased by the treatment in all groups compare to the control. Cells treated with AmB + allicin had a greater adhesive force than cells treated with AmB alone because of the secretion of molecules due to collapsed membranes. All cells treated with allicin or drugs were softer than the control cells. These results suggest that allicin can reduce MIC of AmB while keeping the same efficacy.


Lack of the HLA-DR2 specificity in multifocal choroiditis and panuveitis.
The prevalence of the HLA-B7 and HLA-DR2 specificities in 17 unrelated patients with multifocal choroiditis and panuveitis, 11 with and six without subretinal neovascularisation, was evaluated and compared with those of two different groups. The first group was 17 patients with subretinal neovascularisation associated with presumed ocular histoplasmosis syndrome, and the second was a group of 105 eye patients with no retinal disease. HLA-DR2 was not found in any patient with multifocal choroiditis and panuveitis, but it was found in 13 patients with presumed ocular histoplasmosis syndrome (p = 6.72 x 10(-5), comparison of the groups with subretinal neovascularisation). The lack of HLA-DR2 was also significant in comparison with the control group of eye patients (p = 0.041). This study suggests that patients with multifocal choroiditis and panuveitis and presumed ocular histoplasmosis syndrome have differing genetic predispositions, though the fundus pictures in these entities have many similarities.


Intensity-modulated radiation therapy for early-stage breast cancer: is it ready for prime time?
Whole breast external beam radiotherapy (WBEBRT) is commonly used as an essential arm in the treatment management of women with early-stage breast cancer. Dosimetry planning for conventional WBEBRT typically involves a pair of tangential fields. Advancement in radiation technology and techniques has the potential to improve treatment outcomes with clinically meaningful long-term benefits. However, this advancement must be balanced with safety and improved efficacy. Intensity-modulated radiation therapy (IMRT) is an advanced technique that shows promise in improving the planning process and radiation delivery. Early data on utilizing IMRT for WBEBRT demonstrate more homogenous dose distribution with reduction in organs at risk doses. This translates to toxicities reduction. The two common descriptors for IMRT are forward-planning "fields in field" and inverse planning. Unlike IMRT for other organs, the aim of IMRT for breast planning is to achieve dose homogeneity and not organ conformality. The aim of this paper was to evaluate whether IMRT is ready for prime time based on these three points: 1) workload impact, 2) the clinical impact on the patient's quality of life, and 3) the appropriateness and applicability to clinical practice.


Analgesic efficacy of low-dose diclofenac versus paracetamol and placebo in postoperative dental pain.
To compare the efficacy and safety of diclofenac-K (12.5 mg) vs paracetamol (500 mg) and placebo given in a flexible dosage regimen to treat pain resulting from extraction of impacted third molar teeth. This was a 2-day, double-blind, double-dummy, randomized, parallel-group, placebo-controlled study of diclofenac-K (12.5 mg) tablets vs paracetamol (500 mg) tablets and placebo in patients with moderate or severe pain within 8 hours of extraction of impacted third molars. After the first 2-tablet dose, patients took on average 2.5 additional tablets of diclofenac-K or 2.4 tablets of paracetamol, almost all as 1-tablet doses. Most placebo patients discontinued by taking rescue medication (ibuprofen 200 mg) on the first day. Pain relief after the initial dose of diclofenac-K (2 x 12.5 mg) was superior to placebo (P < .01 for all efficacy outcomes) and comparable to paracetamol (2 x 500 mg). About 30% of patients in each active treatment group took rescue medication during the study, compared to 78% on placebo. About 70% in each active treatment group considered the overall pain relief to be "some," "a lot," or "complete" compared to only 15% on placebo. The incidence of adverse events in each active treatment group was low and comparable between the treatments. An initial double-dose of diclofenac-K (2 x 12.5 mg) or paracetamol (2 x 500 mg) adequately relieved the most intense postoperative pain, and the flexible multiple dose regimen (1 or 2 tablets) maintained adequate pain relief thereafter. Most patients needed only 1-tablet doses following the initial 2-tablet dose.


[Combination chemotherapy with bleomycin ointment and lysozyme ointment against mouse WHT squamous cell carcinoma].
The antitumor effect of bleomycin (BLM) ointment in combination with lysozyme (LY) ointment was investigated. Nine-week-old male and female WHT/Ht mice were implanted with a graft of WHT squamous cell carcinoma into the subcutis of back, and the skin covering the developed solid tumor was resected 7 days after implantation. Thereafter, the mice were administered twice daily for 7 days with each of the following: 220 mg of 0.25% BLM ointment, 2.5% LY ointment, and a 1:1 mixture of 0.5% BLM ointment plus 5% LY ointment. BLM ointment and the combination of BLM ointment and LY ointment were effective with an inhibition rate of 79.3 and 89.7%, respectively. The inhibition rates of these groups showed a statistically significant increase over that of control group. Further, the rate of the combination group displayed a statistically significant increase over that of the BLM ointment group. Formation of crusta on the solid tumor was markedly inhibited in the groups applied LY ointment and the combination of LY ointment and BLM ointment. LY was ineffective against cultured cells of WHT squamous cell carcinoma and did not potentiate the antitumor activity of BLM in combination. These results suggest that potentiation of the antitumor effect of BLM ointment in combination with LY ointment is due to inhibition of crusta formation by LY resulting in an increased permeation of BLM into tumor tissue.


Enhanced phagocytosis and complement-mediated killing of Mannheimia haemolytica serotype 1 following in-frame CMP-sialic acid synthetase (neuA) gene deletion.
Mannheimia haemolytica is the most significant bacterial pathogen associated with the bovine respiratory disease complex. Although sialic acid is a known virulence factor in other members of Pasteurellaceae, such as Histophilus somni and Pasteurella multocida, the significance of sialic acid to the virulence of M. haemolytica is currently unknown. Therefore, the role of sialic acid as a virulence determinant of M. haemolytica was investigated by constructing an in-frame neuA [CMP-N-acetylneuraminic acid (Neu5Ac/sialic) synthetase] mutant, which was shown by high-performance anion exchange chromatographic analysis (HPAEC) to be devoid of sialic acid on the lipopolysaccharide (LPS). Both the neuA mutant and wild-type parent strains exhibited similar growth rates in the growth curve assay. Real-time qPCR and ELISA evaluation showed no differences in proinflammatory cytokine expressions (IL-1β, IL-6, and IL-8) between the neuA mutant and parent strain when peripheral blood mononuclear cells were incubated with LPS. Interestingly, the neuA mutant was three to four logs more sensitive to a whole-blood bacterial killing assay than the parent strain. Similar results were also observed in plasma and serum bacterial killing assays. Flow cytometry analyses showed higher uptake of neuA mutant by phagocytes, compared to the parent strain, in the whole-blood phagocytosis assay; however, no difference in reactive oxygen species production in neutrophils or monocytes was detected for either strain. Taken together, these results indicate that sialylation of M. haemolytica LPS plays a vital role in reducing complement-mediated and phagocytic killing. IMPORTANCE The Gram-negative coccobacillus Mannheimia haemolytica is a natural inhabitant of the upper respiratory tract in ruminants and the most common bacterial agent involved in bovine respiratory disease complex development. Key virulence factors harbored by M. haemolytica are leukotoxin, lipopolysaccharide, capsule, adhesins, and neuraminidase which are involved in evading innate and adaptive immune responses. In this study, we have shown that CMP-sialic acid synthetase (neuA) is necessary for the incorporation of sialic acid onto the membrane, and inactivation of neuA results in increased phagocytosis and complement-mediated killing of M. haemolytica, thus demonstrating that sialylation contributes to the virulence of M. haemolytica.


Differentiating Sexual From Other Violent Offence Types for Case Assessment, Planning, and Management.
Core components of the Intake Assessment (IA) process in the Canadian federal corrections system were examined to determine whether a simplified algorithmic equation for individuals sentenced for sex crimes could be tailored and differentiated from other violent offence types. Two major offence type categories, namely sexual and other violent were constructed for 2,896 adult male first releases for 2016 to 2017 and 2017 to 2018. A restricted set of static risk indicators, dynamic need ratings, and other actuarial measures as well as whether or not there were any returns to federal custody were extracted for each case. A combined risk index yielded robust predictions of custodial return for sexual and other violent offence types with significant and robust AUCs of 0.77 and 0.71, respectively. Analyses showed that five-level risk groupings could be derived independently for the two offence type categorizations.


Wilms tumor occurring as a botryoid renal pelvicalyceal mass.
Wilms tumor usually occurs as an abdominal mass arising from the renal parenchyma. A case was encountered in which the neoplasm filled the pelvicalyceal system of an 8-year-old boy as a botryoid mass, with minimal parenchymal involvement. The radiologic manifestations, pathologic features, and surgical implications are discussed.


One-stage anatomic double bundle anterior and posterior cruciate ligament reconstruction.
Main evidence of the heavy knee dislocations is the rupture of both Anterior Cruciate Ligament (ACL) and Posterior Cruciate Ligament (PCL). There are limited sources for the treatment of both ligaments at a single stage. Materials-method: One-staged anatomic double-bundle ACL and PCL reconstruction technique has been applied to 2 cases aged 20 and 36 with traumatic knee dislocation. Lateral collateral ligament and posteriolateral corner reconstruction added to one case, and medial collateral ligament and posteriomedial corner reconstruction for the other case. Because of additional femur fractures of the both cases, ligament reconstructions have been applied after the main treatment. Anterior tibialis tendon (ATT) allograft has been used for graft for both cases because of other stabilization deficiencies of knees. It has been confirmed that femoral and tibial tunnels constructed with anatomic double-bundle technique are fitting to anatomic locations by the post-operation CT results. Post fixation screw has been used for tibia, and endobutton at femur. Tracking records of patients at 8th month shows that; Lysholm score of the case aged 20 was 89, and 85 for the case aged 36. While KT-1000 values was 3.7 mm, and 4.1 mm for 15 N power; and 9.1 mm-9.6 mm with the maximum power. Surgical technical details of one-staged double-bundle reconstruction for ACL and PCL injuries which is gaining popularity recently has been stated.


Short-Term Volume Loading Effects on Estimated Intracranial Pressure in Human Volunteers.
BACKGROUND: Short-term fluid loading is used as part of post-spaceflight medical procedures and clinical treatment in hospitals. Hypervolemia with hemodilution induced by rapid fluid infusion reportedly impaired dynamic cerebral autoregulation. However, the effects on intracranial pressure (ICP) remain unknown. Therefore, we estimated ICP noninvasively (nICP) to examine whether rapid fluid infusion would raise ICP.METHODS: Twelve healthy male volunteers underwent two discrete normal saline (NS) infusions (15 and 30 ml · kg-1 stages, NS-15 and NS-30, respectively) at a rate of 100 ml · min-1. The cerebral blood flow (CBF) velocity (CBFv) waveform from the middle cerebral artery obtained by transcranial Doppler ultrasonography was recorded, as was the arterial blood pressure (ABP) waveform at the radial artery obtained by tonometry. We then used these waveforms to calculate nICP, cerebral artery compliance, and the pulsatility index (PI) in an intracranial hydraulic model.RESULTS: nICP increased significantly in both infusion stages from preinfusion (preinfusion: 7.6 ± 3.4 mmHg; NS-15: 10.9 ± 3.3 mmHg; NS-30: 11.7 ± 4.2 mmHg). No significant changes were observed in cerebral artery compliance or PI. Although ABP did not change in any stage, CBFv increased significantly (preinfusion: 67 ± 10 cm · s-1; NS-15: 72 ± 12 cm · s-1; NS-30: 73 ± 12 cm · s-1).DISCUSSION: Hypervolemia with hemodilution induced by rapid fluid infusion caused increases in nICP and CBFv. No changes were observed in cerebral artery compliance or PI related to cerebrovascular impedance. These findings suggest that rapid fluid infusion may raise ICP with increased CBF.Kurazumi T, Ogawa Y, Takko C, Kato T, Konishi T, Iwasaki K. Short-term volume loading effects on estimated intracranial pressure in human volunteers. Aerosp Med Hum Perform. 2022; 93(4):347-353.


Induced tolerance to abiotic and biotic stresses of broccoli and Arabidopsis after treatment with elicitor molecules.
The plant hormones salicylic acid (SA) and jasmonic acid (JA) regulate defense mechanisms capable of overcoming different plant stress conditions and constitute distinct but interconnected signaling pathways. Interestingly, several other molecules are reported to trigger stress-specific defense responses to biotic and abiotic stresses. In this study, we investigated the effect of 14 elicitors against diverse but pivotal types of abiotic (drought) and biotic (the chewing insect Ascia monuste, the hemibiotrophic bacterium Pseudomonas syringae DC 3000 and the necrotrophic fungus Alternaria alternata) stresses on broccoli and Arabidopsis. Among the main findings, broccoli pre-treated with SA and chitosan showed the highest drought stress recovery in a dose-dependent manner. Several molecules led to increased drought tolerance over a period of three weeks. The enhanced drought tolerance after triggering the SA pathway was associated with stomata control. Moreover, methyl jasmonate (MeJA) reduced A. monuste insect development and plant damage, but unexpectedly, other elicitors increased both parameters. GUS reporter assays indicated expression of the SA-dependent PR1 gene in plants treated with nine elicitors, whereas the JA-dependent LOX2 gene was only expressed upon MeJA treatment. Overall, elicitors capable of tackling drought and biotrophic pathogens mainly triggered the SA pathway, but adversely also induced systemic susceptibility to chewing insects. These findings provide directions for potential future in-depth characterization and utilization of elicitors and induced resistance in plant protection.


[Seasonal variation in intraocular pressure].
Generally speaking, physicians have the impression that intraocular pressure (IOP) in winter is higher than in summer, but it is very difficult to evaluate the difference between summer and winter IOP statistically, because the treatments of glaucoma patients are changed according to their conditions. We compared the winter and summer IOP of normal subjects and of several glaucoma patients who had no therapy or no change in therapy. The subjects were divided into four groups, i.e., 20 eyes of the normal group, 17 eyes of the ocular hypertensive group, 24 eyes of the primary open angle glaucoma group, and 52 eyes of the low tension glaucoma group. The difference in mean IOP between summer and winter were evaluated for each subject. In all groups, the mean difference in mean winter IOP was significantly higher. The ups and downs of IOP were greater in the ocular hypertensive group and the primary open angle glaucoma group than in the normal group and the low tension glaucoma group. These results suggest that the seasonal variation of IOP should be taken in consideration when treating glaucoma patients.


Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation.
Major depressive disorder is often resistant to antidepressant treatment. Repetitive transcranial magnetic stimulation (rTMS) has been used in treatment-resistant depression (TRD). Known adverse events of rTMS include transient headache, local pain, syncope, seizure induction, and hypomania induction. This report outlines a patient with TRD who unexpectedly improved following a seizure during the course of rTMS, which has never been reported.


Resonance shear measurement of nanoconfined ionic liquids.
Two types of imidazolium-based ionic liquid (IL), 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide ([C(4)mim][NTF(2)]) and 1-butyl-3-methylimidazolium tetrafluoroborate ([C(4)mim][BF(4)]), confined between silica surfaces were investigated by surface force apparatus (SFA)-based resonance shear measurements together with surface force measurements. The surface force profiles in the ILs showed oscillatory solvation forces below the characteristic surface separations: 10.0 nm for [C(4)mim][NTf(2)] and 6.9 nm for [C(4)mim][BF(4)]. The more pronounced solvation force found in [C(4)mim][NTf(2)] suggests that the crystal-forming ability of the IL contributes to the stronger layering of the ILs adjacent to the surface. The resonance shear measurement and the physical model analysis revealed that the viscosities of the confined ILs were 1-3 orders of magnitude higher than that of the bulk IL. This paper also focused on the correlation between the resonance shear behaviour and the lubrication property of the ILs, and the suspension rheology in the ILs. An understanding of the solid-IL interface and of ILs confined in nanospace will facilitate the further development of novel applications employing ILs.


Antithrombotic therapies for neurointerventional surgery: a 2021 French comprehensive national survey.
Neurointerventionists lack guidelines for the use of antithrombotic therapies in their clinical practice; consequently, there is likely to be significant heterogeneity in antithrombotic use between centers. Through a nationwide survey, we aimed to obtain an exhaustive cross-sectional overview of antithrombotic use in neurointerventional procedures in France. In April 2021, French neurointerventional surgery centers were invited to participate in a nationwide 51-question survey disseminated through an active trainee-led research collaborative network (the JENI-RC). All 40 centers answered the survey. Fifty-one percent of centers reported using ticagrelor and 43% used clopidogrel as premedication before intracranial stenting. For flow diversion treatment, dual antiplatelet therapy was maintained for 3 or 6 months in 39% and 53% of centers, respectively, and aspirin was prescribed for 12 months or more than 12 months in 63% and 26% of centers, respectively. For unruptured aneurysms, the most common heparin bolus dose was 50 IU/kg (59%), and only 35% of centers monitored heparin activity for dose adjustment. Tirofiban was used in 64% of centers to treat thromboembolic complications. Fifteen percent of these comprehensive stroke centers reported using tenecteplase to treat acute ischemic strokes. Cangrelor appeared as an emergent drug in specific indications. This nationwide survey highlights the important heterogeneity in clinical practices across centers. There is a pressing need for trials and guidelines to further evaluate and harmonize antithrombotic regimens in the neurointerventional field.


Pregnancy-associated cervical cancer: obstetric outcomes.
Describe the obstetric outcomes among women in California with pregnancy associated cervical cancer. Cases were identified utilizing computer-linked infant birth/death certificates, discharge records, and cancer registry files, and then assigned to a prenatal or post-partum cancer diagnosis group. Outcomes included cesarean delivery, hospitalizations, birth weight, prematurity, and infant mortality. Among 434 cases identified, those diagnosed prenatally (136 cases) had higher rates of cesarean section (odds ratio 3.7; 95% CI 2.6, 5.2), hospitalization >5 days (maternal: odds ratio 14.1; 95% CI 9.2, 21.5 neonatal: odds ratio 5.2; 95% CI 3.6, 7.5), low birth weight (LBW) (odds ratio 5.5; 95% CI 3.7, 8.1), very LBW (odds ratio 6.9; 95% CI 3.7, 12.8), prematurity (odds ratio 4.7; 95% CI 3.2, 6.7), and fetal deaths (odds ratio 5.5; 95% CI 2.0, 14.8) compared to non-cancer pregnant controls. Very LBW (odds ratio 2.6; 95% CI 1.4, 4.8), prematurity (odds ratio 1.5; 95% CI 1.1, 2.1), and fetal death rates (odds ratio 3.0; 95% CI 1.2, 7.4) remained elevated among those diagnosed post-partum. No neonatal deaths were attributable to elective premature delivery. We observed higher rates of fetal death and spontaneous prematurity among women with pregnancy-associated cervical cancer.


[Maxillofacial manifestations of Cowden's disease. Apropos of 2 cases].
Two new cases of Cowden's disease observed in two young sisters are reported. The diagnosis was based on the clinical observation of oral mucosa lesions (gingival hyperplasia, papillomatosis, scrotal tongue). In one case, visceral manifestations in childhood were observed. Cowden's disease is a familial affection (autosomal dominant trait) characterized by association of oral mucosa and skin lesions and of multiple hamartomas involving glandular tissues. Clinical and familial history investigations are justified by the high risk of malignant tumors (breast carcinoma).


Clinical Value of Heart Qi in the Treatment of Chronic Heart Failure With Depression.
Chronic heart failure (CHF) is a form of persistent heart failure. If a patient develops depression, it can worsen the severity of heart failure and can lead to adverse outcomes. No researchers have studied the effects of tonic heart qi soup for patients with CHF and depression. The study intended to evaluate the clinical efficacy of tonic heart qi soup in the treatment of chronic heart failure (CHF) for patients with comorbid depression. The research team performed a prospective randomized controlled trial. The study took place in the Department of Chinese Medicine at Cangzhou Central Hospital in Cangzhou, Hebei Province, China. Participants were 120 patients with CHF at the hospital as inpatients or outpatients between January 2016 and January 2019. The research team divided participants into two groups, with 60 patients each: (1) an intervention group, which received conventional Western medical treatment combined with treatment with a commercial tonic heart qi soup and (2) a control group, which received conventional Western medical treatment only. The research team measured: (1) treatment efficacy, (2) cardiac function, (3) adverse reactions, (4) B-type natriuretic peptide (BNP) and Ghrelin, and (5) depression. In the intervention group, 55 participants showed significant improvement in the degree of heart failure, for a total effectiveness rate of 91.67%, which was significantly higher than that of the control group (P = .000). The intervention group had 10 participants in class II, 18 in class III, and 22 in class IV. Among them, 28 participants improved, indicating significantly better outcomes than those of the control group. The intervention group's BNP levels, at 1031.58 ± 118.83 pg/ml, and ghrelin levels, at 481.46 ± 57.53%, were significantly lower than those of the control group. No liver- or renal-function damage, insomnia, or significant adverse reactions occurred for either group. The intervention group's total incidence rate for adverse reactions, at 1.67%, was significantly lower than that of the control group, at 11.67% (P = .000) and also had a higher total effective rate in reducing depression, at 86.67%, compared to that of the control group, at 43.33%. Heart Qi Tonic Tang, as an adjunctive therapy, significantly improved outcomes for CHF patients with depression. It effectively reduced heart failure symptoms, with minimal adverse reactions and increased patient comfort and compliance.


Akkermansia muciniphila Exerts Strain-Specific Effects on DSS-Induced Ulcerative Colitis in Mice.
Akkermansia muciniphila is a commensal bacterium of the gut mucus layer. Although both in vitro and in vivo data have shown that A. muciniphila strains exhibit strain-specific modulation of gut functions, its ability to moderate immunity to ulcerative colitis have not been verified. We selected three isolated human A. muciniphila strains (FSDLZ39M14, FSDLZ36M5 and FSDLZ20M4) and the A. muciniphila type strain ATCC BAA-835 to examine the effects of different A. muciniphila strains on dextran sulfate sodium-induced colitis. All of the A. muciniphila strains were cultured anaerobically in brain heart infusion medium supplemented with 0.25% type II mucin from porcine stomach. To create animal models, colitis was established in C57BL/6 mice which randomly divided into six groups with 10 mice in each group by adding 3% dextran sulfate sodium to drinking water for 7 days. A. muciniphila strains were orally administered to the mice at a dose of 1 × 109 CFU. Only A. muciniphila FSDLZ36M5 exerted significant protection against ulcerative colitis (UC) by increasing the colon length, restoring body weight, decreasing gut permeability and promoting anti-inflammatory cytokine expression. However, the other strains (FSDLZ39M14, ATCC BAA-835 and FSDLZ20M4) failed to provide these effects. Notably, A. muciniphila FSDLZ20M4 showed a tendency to exacerbate inflammation according to several indicators. Gut microbiota sequencing showed that A. muciniphila FSDLZ36M5 supplementation recovered the gut microbiota of mice to a similar state to that of the control group. A comparative genomic analysis demonstrated that the positive effects of A. muciniphila FSDLZ36M5 compared with the FSDLZ20M4 strain may be associated with specific functional genes that are involved in immune defense mechanisms and protein synthesis. Our results verify the efficacy of A. muciniphila in improving UC and provide gene targets for the efficient and rapid screening of A. muciniphila strains with UC-alleviating effects.


Alveolar macrophages as orchestrators of COPD.
Alveolar macrophages play a critical role in the pathophysiology of COPD and are a major target for future anti-inflammatory therapy. Macrophage numbers are markedly increased in the lung and alveolar space of patients with COPD and are localized to sites of alveolar destruction. The increased numbers of macrophages may result from increased recruitment of blood monocytes, prolonged survival in the lung and to a lesser extent to increased proliferation in the lung. Alveolar macrophages from COPD patients have an increased baseline and stimulated secretion of inflammatory proteins, including certain cytokines, chemokines, reactive oxygen species and elastolytic enzymes, which together could account for all of the pathophysiological features of COPD. Alveolar macrophages form COPD appear to be resistant to the anti-inflammatory effects of corticosteriods and this is linked to reduced activity and expression of histone deacetylase 2, a nuclear enzyme that switches off inflammatory genes activated through the transcription factor nuclear factor-KB. Alternative anti-inflammatory therapies that inhibit macrophages are therefore needed in the future to deal with the chronic inflammation of COPD. These drugs may include resveratrol, theophylline derivatives, MAP kinase inhibitors and phosphodiesterase-4 inhibitors.


Influence of human recombinant interferon-alpha2a (rhIFN-alpha2a) on altered lymphocyte subpopulations and monocytes in Behcet's disease.
In Behçet's disease (BD), several abnormalities of lymphocyte subpopulations have been described. Standard treatment comprises immunosuppressive drugs. We successfully treated 50 patients with ocular BD with interferon-alpha2a (IFN-alpha2a) (response rate 92%), although this is counterintuitive because IFN-alpha is immunostimulatory and can sometimes even induce autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis. The aim of the present study was to elucidate the immunomodulatory effects that IFN-alpha might exert on peripheral blood mononuclear cells (PBMC) in BD by examining changes in the distribution of lymphocyte subpopulations under IFN-alpha2a treatment. Fourteen patients with ocular BD were evaluated before and at weeks 4 and 24 of IFN-alpha treatment and compared with 10 healthy controls. PBMC were stained with monoclonal antibodies and measured by flow cytometry. Compared with the controls there is a significant elevation of monocytes (CD14(+)), CD8(+)/gammadelta T cells, CD3(+)/gammadelta T cells, natural killer (NK) cells (CD56(+)/CD16(+)) and activated/regulatory T cells (CD4(+)/CD25(+) and CD8(+)/CD25(+)) in patients with active BD before treatment with IFN-alpha2a. Numbers of naïve T cells (CD8(+)/CD45(+)RA(+)/RO(-), CD4(+)/CD45(+)RA(+)/RO(-)) were significantly lower. Under therapy, NK cells, CD8(+)/gammadelta T cells and CD3(+)/gammadelta T cells decreased significantly, whereas B cells increased. The previously reduced expression of HLA class I on monocytes in HLA-B51-positive patients rose to levels comparable to HLA-B51-negative patients. These results implicate the participation of NK cells and gammadelta T cells, especially CD8(+)/gammadelta T cells, in the pathogenesis of BD and may explain one mechanism by which IFN-alpha2a exerts therapeutic effects. Alternatively, they may result indirectly from remission induction by IFN-alpha2a. The reduced expression of HLA class I on monocytes in HLA-B*51-positive patients might reflect an impaired expression of and antigen presentation by HLA-B*51.


Predictors of proctocolectomy in children with ulcerative colitis.
Few clinical predictors are associated with definitive proctocolectomy in children with ulcerative colitis (UC). The purpose of the present study was to identify clinical predictors associated with surgery in children with UC using a disease-specific database. Children diagnosed with UC at age <18 years were identified using the Pediatric Inflammatory Bowel Disease Consortium (PediIBDC) database. Demographic and clinical variables from January 1999 to November 2003 were extracted alongside incidence and surgical staging. Review of the PediIBDC database identified 406 children with UC. Approximately half were girls (51%) with an average age at diagnosis of 10.6 ± 4.4 years in both boys and girls. Average follow-up was 6.8 (±4.0) years. Of the 57 (14%) who underwent surgery, median time to surgery was 3.8 (interquartile range 4.9) years after initial diagnosis. Children presenting with weight loss (hazard ratio [HR] 2.55, 99% confidence interval [CI] 1.21-5.35) or serum albumin <3.5 g/dL (HR 6.05, 99% CI 2.15-17.04) at time of diagnosis and children with a first-degree relative with UC (HR 1.81, 99% CI 1.25-2.61) required earlier surgical intervention. Furthermore, children treated with cyclosporine (HR 6.11, 99% CI 3.90-9.57) or tacrolimus (HR 3.66, 99% CI 1.60-8.39) also required earlier surgical management. Other symptoms, laboratory tests, and medical therapies were not predictive for need of surgery. Children with UC presenting with hypoalbuminemia, weight loss, a family history of UC, and those treated with calcineurin inhibitors frequently require restorative proctocolectomy for definitive treatment. Early identification and recognition of these factors should be used to shape treatment goals and initiate multidisciplinary care at the time of diagnosis.


[Therapy of Lesniowski-Crohn disease of the upper part of the gastrointestinal tract].
The treatment of a form of Lesniowski-Crohn disease (L-CD) which occurs in the upper part of the gastrointestinal tract (GI) in principle is similar to that which is used if other parts of the GI tract are involved in L-CD, however with certain modifications, and these problems are discussed in this paper. The treatment is based on 5-aminosalicylic acid (5-ASA), glucocorticosteroids, antibiotics and immunosuppressive drugs. For patients in whom the conventional therapy doesn't give expected results, the advent of infliximab (biologic agents) has greatly improved treatment possibilities of L-CD. Lesniowski-Crohn disease is not curable either by drugs or by surgery. The goal of treatment in this disease remains the mitigation of symptoms and improvement of the quality of life and at the same time elimination or delaying of the appearance of complications and early and late side effects as a result of treatment. The introduction of biologic agents into the treatment arsenal for inflammatory bowel diseases is a revolutionary step.


Rituximab in high-grade lymphoma.
In 1997, the approval of the anti-CD20 antibody rituximab heralded a new era of combined immunochemotherapy for the treatment of malignant lymphoma. Until then, a combination of cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) had been the standard of treatment for aggressive B-cell lymphoma for more than 25 years. The addition of rituximab led to an impressive improvement of response rates and survival outcomes in patients with follicular and diffuse large B-cell lymphoma (DLBCL) that has been confirmed in several randomized trials. Remaining challenges in the rituximab era are the identification of the optimal chemotherapy partner with respect to synergistic effects, as well as to the lack of interference with its effector mechanisms. Finally, the question of the optimal dosage and schedule of rituximab has to be addressed in well-designed randomized trials. The outcome of patients relapsing after a rituximab-containing induction regimen is dismal even with high-dose therapy and autologous stem cell transplantation (ASCT). For these patients new modalities of second-line therapy are urgently warranted.


Improved Prediction of Falls in Community-Dwelling Older Adults Through Phase-Dependent Entropy of Daily-Life Walking.
Age and age-related diseases have been suggested to decrease entropy of human gait kinematics, which is thought to make older adults more susceptible to falls. In this study we introduce a new entropy measure, called phase-dependent generalized multiscale entropy (PGME), and test whether this measure improves fall-risk prediction in community-dwelling older adults. PGME can assess phase-dependent changes in the stability of gait dynamics that result from kinematic changes in events such as heel strike and toe-off. PGME was assessed for trunk acceleration of 30 s walking epochs in a re-analysis of 1 week of daily-life activity data from the FARAO study, originally described by van Schooten et al. (2016). The re-analyzed data set contained inertial sensor data from 52 single- and 46 multiple-time prospective fallers in a 6 months follow-up period, and an equal number of non-falling controls matched by age, weight, height, gender, and the use of walking aids. The predictive ability of PGME for falls was assessed using a partial least squares regression. PGME had a superior predictive ability of falls among single-time prospective fallers when compared to the other gait features. The single-time fallers had a higher PGME (p < 0.0001) of their trunk acceleration at 60% of their step cycle when compared with non-fallers. No significant differences were found between PGME of multiple-time fallers and non-fallers, but PGME was found to improve the prediction model of multiple-time fallers when combined with other gait features. These findings suggest that taking into account phase-dependent changes in the stability of the gait dynamics has additional value for predicting falls in older people, especially for single-time prospective fallers.


Spectrum of acute kidney injury in the Himalayan region.
Acute kidney injury (AKI) is common in hospitalized patients and is an important cause of mortality. This is a descriptive study of AKI in patients from Himachal Pradesh, India, located in Western Himalayan region. Over a period of 1 year, 102 patients with clinical and laboratory evidence of azotemia were included. Out of 102 patients, 84.3% had community acquired AKI and 15.7% had hospital acquired AKI. Medical causes were leading contributors (85.3%), with septicemia being the main factor (33.3%). Multiorgan failure was present in 59.8% patients. The overall mortality was 29.2%, and community acquired AKI was associated with higher mortality as compared to hospital-acquired AKI (22.5% vs 6.7%). AKI is still common in community and associated with high mortality. Septicemia, volume depletion and nephrotoxins were the leading cause of AKI in our study. Our study highlights the presence of hypotension, multiorgan failure and oliguria with mortality. Community-acquired AKI had higher mortality than hospital-acquired AKI.


Echocardiographic evaluation of pulmonary artery pressure with clinical correlates in predominantly obese adults.
Pulmonary artery systolic pressure (PASP) was examined in relationship to age, body mass index (BMI), the effects of comorbid disease, and standard echocardiographic measurements of cardiac chamber size, left ventricular filling patterns, and left ventricular systolic function in 5 large cohorts presenting with a primary problem of obesity. For subjects with a measurable PASP, means (+/- SD) across cohorts for age ranged from 46.0 +/- 11.2 to 54.1 +/- 12.8 years, for BMI from 26.0 +/- 4.4 to 37.2 +/- 6.1 kg/m2, and PASP (n = 1515) from 29.9 +/- 7.7 to 33.8 +/- 7.8 mm Hg. PASP 30 mm Hg or greater occurred in 46% to 66% of subjects and 35 mm Hg or greater in 16% to 36%. Age and BMI were the most significant correlates of PASP. Increased PASP was also significantly associated with systemic hypertension and a history of cardiovascular disease. The mean PASP in obese individuals is higher than previously reported with nearly one third having a PASP of 35 mm Hg or greater. Clinical interpretation of PASP should include BMI, age, blood pressure, and presence of cardiovascular disease.


Whole-genome sequencing as an investigational device for return of hereditary disease risk and pharmacogenomic results as part of the All of Us Research Program.
The All of Us Research Program (AoURP, "the program") is an initiative, sponsored by the National Institutes of Health (NIH), that aims to enroll one million people (or more) across the USA. Through repeated engagement of participants, a research resource is being created to enable a variety of future observational and interventional studies. The program has also committed to genomic data generation and returning important health-related information to participants. Whole-genome sequencing (WGS), variant calling processes, data interpretation, and return-of-results procedures had to be created and receive an Investigational Device Exemption (IDE) from the United States Food and Drug Administration (FDA). The performance of the entire workflow was assessed through the largest known cross-center, WGS-based, validation activity that was refined iteratively through interactions with the FDA over many months. The accuracy and precision of the WGS process as a device for the return of certain health-related genomic results was determined to be sufficient, and an IDE was granted. We present here both the process of navigating the IDE application process with the FDA and the results of the validation study as a guide to future projects which may need to follow a similar path. Changes to the program in the future will be covered in supplementary submissions to the IDE and will support additional variant classes, sample types, and any expansion to the reportable regions.


The antioxidative activity of piceatannol and its different derivatives: Antioxidative mechanism analysis.
The naturally occurring stilbenes piceatannol and its derivatives are excellent antioxidants. In this work, the antioxidative activities of piceatannol and different piceatannol derivatives have been investigated using the density functional theory (DFT) method based on three widely accepted radical scavenging mechanisms, namely, the hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET). The gas and four solvent phases, namely, bond dissociation enthalpy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), proton affinity (PA) and electron transfer enthalpy (ETE), related to these mechanisms were calculated to elucidate the antioxidative capacities of the investigated compounds. This work focuses specifically on the thermodynamically preferred mechanism, antioxidative site and antioxidative activity order of the investigated stilbenes. The substituted effects of the methyl group and prenyl group on the chemical properties of the remaining OH and CH groups are also analysed. This work confirms the vital role of the OH and CH groups on free radical scavenging of piceatannol and its derivatives.


Run-to-Run Optimization Control Within Exact Inverse Framework for Scan Tracking.
A run-to-run optimization controller uses a reduced set of measurement parameters, in comparison to more general feedback controllers, to converge to the best control point for a repetitive process. A new run-to-run optimization controller is presented for the scanning fiber device used for image acquisition and display. This controller utilizes very sparse measurements to estimate a system energy measure and updates the input parameterizations iteratively within a feedforward with exact-inversion framework. Analysis, simulation, and experimental investigations on the scanning fiber device demonstrate improved scan accuracy over previous methods and automatic controller adaptation to changing operating temperature. A specific application example and quantitative error analyses are provided of a scanning fiber endoscope that maintains high image quality continuously across a 20 °C temperature rise without interruption of the 56 Hz video.


Spherical molecularly imprinted polymer particles: a promising tool for molecular recognition in capillary electrokinetic separations.
Spherical molecularly imprinted polymer particles obtained via precipitation polymerization, were introduced as a pseudostationary phase in capillary electrophoresis (CE) to study molecular recognition. Analyses were performed via a partial filling technique using (+)-ephedrine-imprinted microspheres (100-200 nm) which were polymerized from methacrylic acid and 1,1,1-Tris(hydroxymethyl)propanetrimethacrylate using acetonitrile as the solvent. The influence of pH and the modifier content on the separation was investigated. A 0.1% w/v suspension in an aqueous 10 mM phosphate buffer (pH 2.5 with 40% acetonitrile) was hydrodynamically injected into the CE system (80% of the effective capillary length) and led to full baseline separation of racemic ephedrine within 10 min.


Immobilized rhodanese: some aspects of anion inhibition kinetics and modulation by cations.
The rat liver rhodanese (thiosulphate: cyanide sulfurtransferase EC 22.214.171.124) has been immobilized on polyacrylamide gels. The immobilized enzyme had a pH optimum of 7.4 and Km values of 3.25 mM and 1.12 mM for S2O3(2-) and KCN, respectively. The enzyme was competitively inhibited by NaNO2 and CH3COONa and noncompetitively by amyl-nitrite. A modulation of activity was observed in the presence of Ca2+, Zn2+, and Cu2+. The results are discussed in line with the detoxicating function of liver rhodanese.


Occurrence of heavy elements in street dust from sub/urban zone of Tianjin: pollution characteristics and health risk assessment.
Main purpose of this study was to determine the concentrations of selected heavy elements (As, Cd, Pb, Cu, Co, Cr and Ni) in the street dust samples (n = 49) collected from seven districts located in suburban/urban zone of Tianjin in order to estimate their possible sources and degree of environmental pollution as well as human health risk. Mean concentrations (mg kg-1) of As (19.3), Cd (0.60), Pb (28.4) and Cu (62.7) were above their corresponding soil background values. According to the results of multivariate statistical analysis, the accumulation of As, Cd, Pb, Cu and Cr in street dust was affected by anthropogenic activities, while the contents of Ni and Co were associated with natural sources. Pollution degree by geo-accumulation index had the following trend: Cd > Cu > As > Pb > Cr > Ni > Co. Dust contamination with Cd ranged from unpolluted to highly polluted. Potential ecological risk indicated low (Pb, Cu, Cr, Co and Ni) to high (Cd) risk, while potential risk index showed moderate and very high risks. Non-carcinogenic risk of the studied elements was below safe level (<1). Data obtained in this investigation gave the additional values to the knowledge needed for future monitoring and risk assessment, relating the presence of heavy elements studied in suburban/urban areas.


Genome-wide evaluation of genetic diversity and linkage disequilibrium in winter and spring triticale (x Triticosecale Wittmack).
Recent advances in genotyping with high-density markers nowadays enable genome-wide genomic analyses in crops. A detailed characterisation of the population structure and linkage disequilibrium (LD) is essential for the application of genomic approaches and consequently for knowledge-based breeding. In this study we used the triticale-specific DArT array to analyze population structure, genetic diversity, and LD in a worldwide set of 161 winter and spring triticale lines. The principal coordinate analysis revealed that the first principal coordinate divides the triticale population into two clusters according to their growth habit. The density distributions of the first ten principal coordinates revealed that several show a distribution indicative of population structure. In addition, we observed relatedness within growth habits which was higher among the spring types than among the winter types. The genome-wide analysis of polymorphic information content (PIC) showed that the PIC is variable among and along chromosomes and that especially the R genome of spring types possesses a reduced genetic diversity. We also found that several chromosomes showed regions of high genetic distance between the two growth habits, indicative of divergent selection. Regarding linkage disequilibrium, the A and B genomes showed a similar LD of 0.24 for closely linked markers and a decay within approximately 12 cM. LD in the R genome was lower with 0.19 and decayed within a shorter map distance of approximately 5 cM. The extent of LD was generally higher for the spring types compared to the winter types. In addition, we observed strong variability of LD along the chromosomes. Our results confirm winter and spring growth habit are the major contributors to population structure in triticale, and a family structure exists in both growth types. The specific patterns of genetic diversity observed within these types, such as the low diversity on some rye chromosomes of spring habits, provide a basis for targeted broadening of the available breeding germplasm. In addition, the genome-wide analysis of the extent and the pattern of LD will assist scientists and breeders alike in the implementation and the interpretation of association mapping in triticale.


Effects of Intraoperative Dexmedetomidine on Postoperative Pain in Highly Nicotine-Dependent Patients After Thoracic Surgery: A Prospective, Randomized, Controlled Trial.
To investigate the effects of intraoperative dexmedetomidine on pain in highly nicotine-dependent patients after thoracic surgery.Highly nicotine-dependent men underwent thoracic surgery and received postoperative patient-controlled intravenous analgesia with sufentanil. In dexmedetomidine group (experimental group, n = 46), dexmedetomidine was given at a loading dose of 1 μg/kg for 10 minutes, followed by continuous infusion at 0.5 μg/kg/h until 30 minutes before the end of surgery. The saline group (control group, n = 48) received the same volume of saline. General anesthesia was administered via a combination of inhalation and intravenous anesthetics. If necessary, patients were administered a loading dose of sufentanil by an anesthesiologist immediately after surgery (0 hours). Patient-controlled analgesia was started when the patient's resting numerical rating scale (NRS) score was less than 4. Resting and coughing NRS scores and sufentanil dosage were recorded 0, 1, 4 hours, and every 4 hours until 48 hours after surgery. Dosages of other rescue analgesics were converted to the sufentanil dosage. Surgical data, adverse effects, and degree of satisfaction were obtained.Cumulative sufentanil dosage, resting NRS, and coughing NRS in the first 24 hours after surgery and heart rate were lower in the experimental compared with the control group (P <0.05). No patient experienced sedation or respiratory depression. Frequency of nausea and vomiting and degree of satisfaction were similar in both groups.Intraoperative dexmedetomidine was associated with reduced resting and coughing NRS scores and a sufentanil-sparing effect during the first 24 hours after thoracic surgery.


Purification of malted-barley endo-beta-D-glucanases by ion-exchange chromatography: some properties of an endo-barley-beta-D-glucanase.
Two endo-beta-D-glucanases which act, respectively, on (1 leads to 3)-beta-D-glucans and barley beta-D-glucan have been isolated from malted barley, and purified by ion-exchange chromatography. The latter enzyme is highly specific for barley beta-D-glucan, and has no action on either (1 leads to 3)- or (1 leads to 4)-beta-D-glucans. It will also act on dyed barley-beta-D-glucan. Certain group-specific reagents inhibit the endo-barley-beta-D-glucanase and the endo-(1 leads to 3)-beta-D-glucanase to similar extents.


[Monitoring Blood Markers to Predict Nivolumab Effectiveness in Esophageal Carcinoma].
We investigated whether monitoring the neutrophil-lymphocyte ratio(NLR)and serum interleukin 2 receptor-%lymphocyte ratio(sIL-2R/%Ly)could predict nivolumab(NIVO)effectiveness in treating 9 patients with esophageal cancer. The progression-free survival(PFS)was 292±44 days and overall survival(OS)was 456±136 days. One patient who had chemotherapy intolerance and switched to NIVO achieved CR, and the others had PD. Four patients had irAEs, which did not correlate with the treatment response. Patients with pretreatment low sIL-2R/%Ly and no NLR increase during treatment had significantly longer OS and better prognosis. Therefore, host parameters, such as NLR, sIL-2R, and lymphocyte counts, were significant in the real time monitoring of NIVO therapy for esophageal carcinoma.


Luteolin Treatment Protects against Renal Ischemia-Reperfusion Injury in Rats.
Renal ischemia-reperfusion (I/R) injury is a common but severe scientific problem. Luteolin has great anti-inflammatory and antioxidant effects. In this study, we studied the effect of luteolin on renal I/R injury in rats. Intragastric administration of luteolin or saline was performed in Sprague-Dawley rats before (40 mg/kg for three days) and after (one day) renal I/R modeling. Kidney and blood samples were harvested to detect the severity of renal injury 24 hours after operation. The results showed that luteolin-treated rats exhibited milder histomorphological changes with lower scores of renal histological lesions; lower blood urea nitrogen and creatinine levels; lower renal malondialdehyde (MDA), 8-oxo-deoxyguanosine (8-OHdG), and myeloperoxidase (MPO) levels; and higher superoxide dismutase (SOD) and catalase (CAT) activities in the kidney. Luteolin attenuated the increased levels of serum and renal tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, renal high mobility group box-1 (HMGB1), and nuclear factor kappa β (NF-κB) expression levels in I/R rats. Furthermore, luteolin treatment significantly reduced renal cell apoptosis and endoplasmic reticulum (ER) stress caused by renal I/R injury. In conclusion, luteolin improved renal function in I/R rats by reducing oxidative stress, neutrophil infiltration, inflammation, renal cell apoptosis, and expression of HMGB1 and NF-κB, and ER stress.


[Emergency operation and perioperative management for a patient with strangulated ileus and shock associated with Rubinstein-Taybi syndrome].
A 21-year-old white male with Rubinstein-Taybi syndrome (RTS) underwent emergency laparotomy and volvulus reduction for a strangulated ileus. Low blood pressure, rapid heart rate and dusky skin color indicated that he was in a hypovolemic and/or septic shock state. Communication with the patient was impossible because of severe mental retardation, deafness, and blindness, and he was quite combative and agitated. Because of an urgent situation and in anticipation of a great risk of regurgitation, no sedatives or anesthetics were used for induction of anesthesia. A large dose of vecuronium with a priming principle technique was the only agent used for endotracheal intubation. Vigorous fluid replacement and appropriate catecholamine therapy were required for the perioperative management and recovery from the shock state. Any cardiac episodes which have been reported in patients with RTS, such as supra-ventricular or ventricular arrhythmia, did not occur throughout the perioperative period. Lack of communication with the patient was an obstacle in the postoperative care, such as respiratory management or the estimation for the timing of extubation. In conclusion, the preparations for a possibly difficult airway and the possible occurrence of arrhythmia were thought to be prudent for the management of the patient with RTS.


Cnf1 Variants Endowed with the Ability to Cross the Blood-Brain Barrier: A New Potential Therapeutic Strategy for Glioblastoma.
Among gliomas, primary tumors originating from glial cells, glioblastoma (GBM) identified as WHO grade IV glioma, is the most common and aggressive malignant brain tumor. We have previously shown that the Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1) is remarkably effective as an anti-neoplastic agent in a mouse model of glioma, reducing the tumor volume, increasing survival, and maintaining the functional properties of peritumoral neurons. However, being unable to cross the blood-brain barrier (BBB), CNF1 requires injection directly into the brain, which is a very invasive administration route. Thus, to overcome this pitfall, we designed a CNF1 variant characterized by the presence of an N-terminal BBB-crossing tag. The variant was produced and we verified whether its activity was comparable to that of wild-type CNF1 in GBM cells. We investigated the signaling pathways engaged in the cell response to CNF1 variants to provide preliminary data to the subsequent studies in experimental animals. CNF1 may represent a novel avenue for GBM therapy, particularly because, besides blocking tumor growth, it also preserves the healthy surrounding tissue, maintaining its architecture and functionality. This renders CNF1 the most interesting candidate for the treatment of brain tumors, among other potentially effective bacterial toxins.


Attraction of spiral waves by localized inhomogeneities with small-world connections in excitable media.
Trapping and untrapping of spiral tips in a two-dimensional homogeneous excitable medium with local small-world connections are studied by numerical simulation. In a homogeneous medium which can be simulated with a lattice of regular neighborhood connections, the spiral wave is in the meandering regime. When changing the topology of a small region from regular connections to small-world connections, the tip of the spiral waves is attracted by the small-world region, where the average path length declines with the introduction of long distant connections. The "trapped" phenomenon also occurs in regular lattices where the diffusion coefficient of the small region is increased. The above results can be explained by the eikonal equation, the Luther equation, and the relation between the core radius and the diffusion coefficient.


The Be-Well Study: a prospective cohort study of lifestyle and genetic factors to reduce the risk of recurrence and progression of non-muscle-invasive bladder cancer.
Bladder cancer is one of the top five cancers diagnosed in the U.S. with a high recurrence rate, and also one of the most expensive cancers to treat over the life-course. However, there are few observational, prospective studies of bladder cancer survivors. The Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study) is a National Cancer Institute-funded, multi-center prospective cohort study of non-muscle-invasive bladder cancer (NMIBC) patients (Stage Ta, T1, Tis) enrolled from the Kaiser Permanente Northern California (KPNC) and Southern California (KPSC) health care systems, with genotyping and biomarker assays performed at Roswell Park Comprehensive Cancer Center. The goal is to investigate diet and lifestyle factors in recurrence and progression of NMIBC, with genetic profiles considered, and to build a resource for future NMIBC studies. Recruitment began in February 2015. As of 30 June 2018, 1,281 patients completed the baseline interview (774 KPNC, 511 KPSC) with a recruitment rate of 54%, of whom 77% were male and 23% female, and 80% White, 6% Black, 8% Hispanic, 5% Asian, and 2% other race/ethnicity. Most patients were diagnosed with Ta (69%) or T1 (27%) tumors. Urine and blood specimens were collected from 67% and 73% of consented patients at baseline, respectively. To date, 599 and 261 patients have completed the 12- and 24-month follow-up questionnaires, respectively, with additional urine and saliva collection. The Be-Well Study will be able to answer novel questions related to diet, other lifestyle, and genetic factors and their relationship to recurrence and progression among early-stage bladder cancer patients.


Measurement with microscopic MRI and simulation of flow in different aneurysm models.
The impact and the development of aneurysms depend to a significant degree on the exchange of liquid between the regular vessel and the pathological extension. A better understanding of this process will lead to improved prediction capabilities. The aim of the current study was to investigate fluid-exchange in aneurysm models of different complexities by combining microscopic magnetic resonance measurements with numerical simulations. In order to evaluate the accuracy and applicability of these methods, the fluid-exchange process between the unaltered vessel lumen and the aneurysm phantoms was analyzed quantitatively using high spatial resolution. Magnetic resonance flow imaging was used to visualize fluid-exchange in two different models produced with a 3D printer. One model of an aneurysm was based on histological findings. The flow distribution in the different models was measured on a microscopic scale using time of flight magnetic resonance imaging. The whole experiment was simulated using fast graphics processing unit-based numerical simulations. The obtained simulation results were compared qualitatively and quantitatively with the magnetic resonance imaging measurements, taking into account flow and spin-lattice relaxation. The results of both presented methods compared well for the used aneurysm models and the chosen flow distributions. The results from the fluid-exchange analysis showed comparable characteristics concerning measurement and simulation. Similar symmetry behavior was observed. Based on these results, the amount of fluid-exchange was calculated. Depending on the geometry of the models, 7% to 45% of the liquid was exchanged per second. The result of the numerical simulations coincides well with the experimentally determined velocity field. The rate of fluid-exchange between vessel and aneurysm was well-predicted. Hence, the results obtained by simulation could be validated by the experiment. The observed deviations can be caused by the noise in the measurement and by the limited resolution of the simulation. The resulting differences are small enough to allow reliable predictions of the flow distribution in vessels with stents and for pulsed blood flow.


Partial associations of dietary iron, smoking and intestinal bacteria with colorectal cancer risk.
Smoking and high red meat intake have been associated with colorectal cancer (CRC) risk. Increased iron exposure may be a common factor, favoring the colonization of certain bacterial pathogens that preferentially grow in an iron-rich luminal environment. We analyzed the data from a population-based case-control study of CRC and measured antibody levels against flagelin of Salmonella (FliC), one of the irontrophic bacteria, in 2 independent blood collections. The risk of CRC synergistically increased by combined exposures to heme iron intake and pack-yr (PY) of cigarette smoking (P value for the interaction = 0.039 on the continuous scale). There was a marginally significant interaction between heme iron intake and PY in increasing FliC antibody in the U.S. control subjects (P = 0.055), although no iron or smoking data were available for Dutch samples. Furthermore, FliC antibody levels were significantly higher in patients with colorectal polyps and cancer than in controls in both Dutch (3.93 vs. 2.23) (P = 0.014) and U.S. samples (6.65 vs. 4.37) (P < 0.001). Potential roles of iron from cigarette smoking and dietary heme in CRC through altering irontrophic luminal bacterial population may warrant further investigation.