Disseminated Gonococcal Infection: An Unusual Presentation Resembling a Lupus Flare.

We present a misdiagnosed case of disseminated gonococcal infection (DGI) in a patient with pre-existing systemic lupus erythematosus (SLE), complaining of sudden onset polyarthralgia and tenosynovitis. Neisseria gonorrhoeae is a common sexually transmitted disease. It can present in young adults as cervicitis and urethritis but is often asymptomatic. In rare instances, gonorrhea can advance to DGI with symptoms such as tenosynovitis, dermatitis, and polyarthralgias, seen most commonly in the knees, ankles, elbows, fingers, and toes. Once suspected, DGI is definitively diagnosed with blood cultures or synovial fluid analysis. SLE is associated with an increased risk of disseminated infections, including DGI. Therefore, early diagnosis of DGI is critical for successful treatment and recovery. Providers should therefore be conscientious of the overlap in symptoms between DGI and a lupus flare. The purpose of examining this case is to encourage the inclusion of disseminated N. gonorrhoeae infection as a differential diagnosis in SLE patients presenting with acute arthralgias regardless of genitourinary symptoms.

A systematic review on potential anticancer activities of Ficus carica L. with focus on cellular and molecular mechanisms.

BACKGROUND: Many substances derived from nutritional or medicinal plants have been studied for their chemopreventive and antineoplastic properties. Among those studied, Ficus carica has shown to have a significant ability to inhibit tumor formation and development of cancer cells through modulating various signaling mechanisms and interaction including a large number of cell signaling molecules. PURPOSE: The goal of this study is to provide a critical and complete evaluation of F. carica's anticancer capacity in various malignancies, as well as related molecular targets. METHODS: Research was conducted electronically on scholarly scientific databases, including Science Direct, PubMed, and Scopus. Published papers were analyzed and investigated using the keywords, Ficus carica, figs, cancer, malignancies and tumor based on established selection criteria. In this systematic review, 27 individual studies were considered. RESULTS: Treatment with F. carica alone or in combination with other medications was linked to anticancer activity with significant evidence. Furthermore, F. carica has been shown to use multitargeted pathways to prevent cancer initiation and development by modulating numerous dysregulated signaling cascades involved in cell proliferation, cell cycle regulation, apoptosis, autophagy inflammatory processes, metastasis, invasion, and angiogenesis. CONCLUSION: Our findings suggest that F. carica and its phytochemicals have the potential for cancer prevention and therapy. Nonetheless, additional mechanistic studies with pure compounds derived from F. carica and well-designed clinical trials are needed to advance our knowledge to clinical application.

Opening of the Blood-Brain Barrier Using Low-Intensity Pulsed Ultrasound Enhances Responses to Immunotherapy in Preclinical Glioma Models.

PURPOSE: The blood-brain barrier (BBB) inhibits adequate dosing/penetration of therapeutic agents to malignancies in the brain. Low-intensity pulsed ultrasound (LIPU) is a safe therapeutic method of temporary BBB disruption (BBBD) to enhance chemotherapeutic delivery to the tumor and surrounding brain parenchyma for treatment of glioblastoma. EXPERIMENTAL DESIGN: We investigated if LIPU could enhance therapeutic efficacy of anti-PD-1 in C57BL/6 mice bearing intracranial GL261 gliomas, epidermal growth factor receptor variant III (EGFRvIII) chimeric antigen receptor (CAR) T cells in NSG mice with EGFRvIII-U87 gliomas, and a genetically engineered antigen-presenting cell (APC)-based therapy producing the T-cell attracting chemokine CXCL10 in the GL261-bearing mice. RESULTS: Mice treated with anti-PD-1 and LIPU-induced BBBD had a median survival duration of 58 days compared with 39 days for mice treated with anti-PD-1, and long-term survivors all remained alive after contralateral hemisphere rechallenge. CAR T-cell administration with LIPU-induced BBBD resulted in significant increases in CAR T-cell delivery to the CNS after 24 (P < 0.005) and 72 (P < 0.001) hours and increased median survival by greater than 129%, in comparison with CAR T cells alone. Local deposition of CXCL10-secreting APCs in the glioma microenvironment with LIPU enhanced T-cell glioma infiltration during the therapeutic window (P = 0.004) and markedly enhanced survival (P < 0.05). CONCLUSIONS: LIPU increases immune therapeutic delivery to the tumor microenvironment with an associated increase in survival and is an emerging technique for enhancing novel therapies in the brain.

Anticancer potential of garlic and its bioactive constituents: A systematic and comprehensive review.

Vegetables of the Allium genus, such as garlic (Allium sativum L.), onions, shallots, leaks, and chives, have been used for many years for food consumption and for medicinal purposes. Historical medical texts have indicated the therapeutic applications of garlic as an antitumor, laxative, diuretic, antibacterial and antifungal agent. Specifically, garlic's antitumor abilities have been traced back 3500 years as a chemotherapeutic agent used in Egypt. Other beneficial effects of garlic consumption include lowering blood pressure, blood cholesterol, sugar and lipids. The processing and aging of garlic result in the production of non-toxic organosulfur by-products. These sulfur-containing compounds, such as allicin, diallyl sulfide, diallyl disulfide, diallyl trisulfide, alliin, S-allylcysteine, and S-allylmercaptocysteine, impact various stages of carcinogenesis. The anticancer mechanisms of action of these garlic-derived phytochemicals include altering mitochondrial permeability, inhibiting angiogenesis, enhancing antioxidative and proapoptotic properties, and regulating cell proliferation. All these effects of garlic's sulfur-compounds have been demonstrated in various human cancers. The intent of this literature research is to explore the potential of garlic-derived products and bioactive organosulfur compounds as cancer chemopreventive and chemotherapeutic agents. This investigation employs criteria for systematic review and critically analyzes published in vitro, in vivo and clinical studies. Concerns and limitations that have arisen in past studies regarding standards of measurement, bioavailability, and method of delivery are addressed. Overall, it is hoped that through this systematic and comprehensive review, future researchers can be acquainted with the updated data assembled on anticancer properties of garlic and its phytoconstituents.

Efficacy of fenugreek seed extract on men's psychological and physical health: a randomized placebo-controlled double-blind clinical trial.

OBJECTIVES: Limited research has examined the effects of fenugreek (Trigonella foenum-graecum L.) supplementation to improve healthy younger men's aging male symptoms. The study objective was to examine whether a fenugreek seed extract would improve healthy men's aging male symptoms, health-related quality of life (HRQoL), grip strength, and anxiety. METHODS: Randomized double-blind placebo-controlled trial was employed, using a parallel design, with assessments at baseline, Day 30, and Day 60. Healthy male volunteers (n = 57, mean age = 26.1 years) were randomized to: fenugreek 400 mg/d (n = 19), fenugreek 500 mg/d (n = 19), or placebo group (n = 19). RESULTS: The fenugreek groups reported significant improvements in aging male symptoms, anxiety levels, grip strength, and indicators of HRQoL compared to the placebo group, p's < 0.05. No adverse events were reported. CONCLUSION: Fenugreek supplementation is an effective nutritional intervention for improving aging male symptoms, anxiety levels, grip strength, and aspects of HRQoL in healthy recreationally active men. Future researchers are encouraged to examine the health and ergogenic effects of fenugreek supplementation in hypogonadal and older populations. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03528538.

Recurrent binge ethanol is associated with significant loss of dentate gyrus granule neurons in female rats despite concomitant increase in neurogenesis.

Binge drinking is becoming increasingly common among American women and girls. We have previously shown significant cell loss, downregulation of neurotrophins and microgliosis in female rats after a single 4-day ethanol exposure. To determine whether recurrent binge exposure would produce similar effects, we administered ethanol (5 g/kg) or iso-caloric control diet once-weekly for 11 weeks to adult female rats. As we have previously shown exercise neuroprotection against binge-induced damage, half the rats were given access to exercise wheels. Blood ethanol concentration (BEC) did not differ between sedentary and exercised groups, nor did it change across time. Using stereology, we quantified the number and/or size of neurons in the medial prefrontal cortex (mPFC) and hippocampal dentate gyrus (DG), as well as the number and activation state of microglia. Binged sedentary rats had significant cell loss in the dentate gyrus, but exercise eliminated this effect. Compared to sedentary controls, sedentary binged rats and all exercised rats showed increased neurogenesis in the DG. Number and nuclear volume of neurons in the mPFC were not changed. In the hippocampus and mPFC, the number of microglia with morphology indicative of partial activation was increased by recurrent binge ethanol and decreased by exercise. In summary, we show significant binge-induced loss of DG granule neurons despite increased neurogenesis, suggesting an unsuccessful compensatory response. Although exercise eliminated cell loss, our results indicate that infrequent, but recurrent exposure to clinically relevant BEC is neurotoxic.

Sex differences in hippocampal damage, cognitive impairment, and trophic factor expression in an animal model of an alcohol use disorder.

Compared to men, women disproportionally experience alcohol-related organ damage, including brain damage, and while men remain more likely to drink and to drink heavily, there is cause for concern because women are beginning to narrow the gender gap in alcohol use disorders. The hippocampus is a brain region that is particularly vulnerable to alcohol damage, due to cell loss and decreased neurogenesis. In the present study, we examined sex differences in hippocampal damage following binge alcohol. Consistent with our prior findings, we found a significant binge-induced decrement in dentate gyrus (DG) granule neurons in the female DG. However, in the present study, we found no significant decrement in granule neurons in the male DG. We show that the decrease in granule neurons in females is associated with both spatial navigation impairments and decreased expression of trophic support molecules. Finally, we show that post-binge exercise is associated with an increase in trophic support and repopulation of the granule neuron layer in the female hippocampus. We conclude that sex differences in alcohol-induced hippocampal damage are due in part to a paucity of trophic support and plasticity-related signaling in females.

Investigation of Sex Differences in the Microglial Response to Binge Ethanol and Exercise.

The female brain appears selectively vulnerable to the neurotoxic effects of alcohol, but the reasons for this are unclear. One possibility is an exaggerated neuroimmune response in the female brain, such that alcohol increases microglia number and reactivity to subsequent stimuli, such as exercise. It is important to better characterize the interactive neural effects of alcohol and exercise, as exercise is increasingly being used in the treatment of alcohol use disorders. The present study compared the number of microglia and evidence of their activation in alcohol-vulnerable regions of the brain (medial prefrontal cortex and hippocampus) in male and female rats following binge alcohol and/or exercise. Binge alcohol increased microglia number and morphological characteristics consistent with their activation in the female brain but not the male, regardless of exercise. Binge alcohol followed by exercise did increase the number of MHC II+ (immunocompetent) microglia in females, although the vast majority of microglia did not express MHC II. These results indicate that binge alcohol exerts sex-specific effects on microglia that may result in enhanced reactivity to a subsequent challenge and in part underlie the apparent selective vulnerability of the female brain to alcohol.

Binge alcohol alters exercise-driven neuroplasticity.

Exercise is increasingly being used as a treatment for alcohol use disorders (AUD), but the interactive effects of alcohol and exercise on the brain remain largely unexplored. Alcohol damages the brain, in part by altering glial functioning. In contrast, exercise promotes glial health and plasticity. In the present study, we investigated whether binge alcohol would attenuate the effects of subsequent exercise on glia. We focused on the medial prefrontal cortex (mPFC), an alcohol-vulnerable region that also undergoes neuroplastic changes in response to exercise. Adult female Long-Evans rats were gavaged with ethanol (25% w/v) every 8h for 4days. Control animals received an isocaloric, non-alcohol diet. After 7days of abstinence, rats remained sedentary or exercised for 4weeks. Immunofluorescence was then used to label microglia, astrocytes, and neurons in serial tissue sections through the mPFC. Confocal microscope images were processed using FARSIGHT, a computational image analysis toolkit capable of automated analysis of cell number and morphology. We found that exercise increased the number of microglia in the mPFC in control animals. Binged animals that exercised, however, had significantly fewer microglia. Furthermore, computational arbor analytics revealed that the binged animals (regardless of exercise) had microglia with thicker, shorter arbors and significantly less branching, suggestive of partial activation. We found no changes in the number or morphology of mPFC astrocytes. We conclude that binge alcohol exerts a prolonged effect on morphology of mPFC microglia and limits the capacity of exercise to increase their numbers.

Ambient temperature influences the neural benefits of exercise.

Many of the neural benefits of exercise require weeks to manifest. It would be useful to accelerate onset of exercise-driven plastic changes, such as increased hippocampal neurogenesis. Exercise represents a significant challenge to the brain because it produces heat, but brain temperature does not rise during exercise in the cold. This study tested the hypothesis that exercise in cold ambient temperature would stimulate hippocampal neurogenesis more than exercise in room or hot conditions. Adult female rats had exercise access 2h per day for 5 days at either room (20 °C), cold (4.5 °C) or hot (37.5 °C) temperature. To label dividing hippocampal precursor cells, animals received daily injections of BrdU. Brains were immunohistochemically processed for dividing cells (Ki67+), surviving cells (BrdU+) and new neurons (doublecortin, DCX) in the hippocampal dentate gyrus. Animals exercising at room temperature ran significantly farther than animals exercising in cold or hot conditions (room 1490 ± 400 m; cold 440 ± 102 m; hot 291 ± 56 m). We therefore analyzed the number of Ki67+, BrdU+ and DCX+ cells normalized for shortest distance run. Contrary to our hypothesis, exercise in either cold or hot conditions generated significantly more Ki67+, BrdU+ and DCX+ cells compared to exercise at room temperature. Thus, a limited amount of running in either cold or hot ambient conditions generates more new cells than a much greater distance run at room temperature. Taken together, our results suggest a simple means by which to augment exercise effects, yet minimize exercise time.

Quantitative 3-D analysis of GFAP labeled astrocytes from fluorescence confocal images.

BACKGROUND: There is a need for effective computational methods for quantifying the three-dimensional (3-D) spatial distribution, cellular arbor morphologies, and the morphological diversity of brain astrocytes to support quantitative studies of astrocytes in health, injury, and disease. NEW METHOD: Confocal fluorescence microscopy of multiplex-labeled (GFAP, DAPI) brain tissue is used to perform imaging of astrocytes in their tissue context. The proposed computational method identifies the astrocyte cell nuclei, and reconstructs their arbors using a local priority based parallel (LPP) tracing algorithm. Quantitative arbor measurements are extracted using Scorcioni's L-measure, and profiled by unsupervised harmonic co-clustering to reveal the morphological diversity. RESULTS: The proposed method identifies astrocyte nuclei, generates 3-D reconstructions of their arbors, and extracts quantitative arbor measurements, enabling a morphological grouping of the cell population. COMPARISON WITH EXISTING METHODS: Our method enables comprehensive spatial and morphological profiling of astrocyte populations in brain tissue for the first time, and overcomes limitations of prior methods. Visual proofreading of the results indicate a >95% accuracy in identifying astrocyte nuclei. The arbor reconstructions exhibited 3.2% fewer erroneous jumps in tracing, and 17.7% fewer false segments compared to the widely used fast-marching method that resulted in 9% jumps and 20.8% false segments. CONCLUSIONS: The proposed method can be used for large-scale quantitative studies of brain astrocyte distribution and morphology.

Selective solar-driven reduction of CO2 to methanol using a catalyzed p-GaP based photoelectrochemical cell.

With rising atmospheric CO2 levels, there has been increasing interest in artificial photosynthetic schemes for converting this greenhouse gas into valuable fuels and small organics. Photoelectrochemical schemes for activating the inert CO2 molecule, however, operate at excessive overpotentials and thus do not convert actual light energy to chemical energy. Here we describe the selective conversion of CO2 to methanol at a p-GaP semiconductor electrode with a homogeneous pyridinium ion catalyst, driving the reaction with light energy to yield faradaic efficiencies near 100% at potentials well below the standard potential.

Patterned assembly of colloidal particles by confined dewetting lithography.

We report the assembly of colloidal particles into confined arrangements and patterns on various cleaned and chemically modified solid substrates using a method which we term "confined dewetting lithography" or CDL for short. The experimental setup for CDL is a simple deposition cell where an aqueous suspension of colloidal particles (e.g., polystyrene spheres) is placed between a floating deposition template (i.e., metal microgrid) and the solid substrate. The voids of the deposition template serve as an array of micrometer-sized reservoirs where several hydrodynamic processes are confined. These processes include water evaporation, meniscus formation, convective flow, rupturing, dewetting, and capillary-bridge formation. We discuss the optimal conditions where the CDL has a high efficiency to deposit intricate patterns of colloidal particles using polystyrene spheres (PS; 4.5, 2.0, 1.7, 0.11, 0.064 microm diameter) and square and hexagonal deposition templates as model systems. We find that the optimization conditions of the CDL method, when using submicrometer, sulfate-functionalized PS particles, are primarily dependent on minimizing attractive particle-substrate interactions. The CDL methodology described herein presents a relatively simple and rapid method to assemble virtually any geometric pattern, including more complex patterns assembled using PS particles with different diameters, from aqueous suspensions by choosing suitable conditions and materials.

Surface modification of indium tin oxide via electrochemical reduction of aryldiazonium cations.

The facile deposition of para-substituted aryl films onto indium-tin oxide (ITO) electrodes by the electrochemical reduction of aryl diazonium salts in acetonitrile is reported. For the deposition conditions used in this report, the aryl film thicknesses are on the order of 1-6 nm, suggesting a multilayer structure. Regardless of the functional group on the aryl diazonium cation, (NO(2), CO(2)H, or fluorene) the electrodeposition behavior onto ITO electrodes is similar to that seen on other electrode materials. XPS and UV-vis data support the introduction of organic functional surface groups to ITO. The blocking behavior of the aryl films on ITO toward the Ru(NH(3))(6)(3+/2+) redox couple is in agreement with electron transfer through conjugated organic layers. The facile preparation of patterned aryl films with regular-spaced 700 nm voids on ITO is also described. Atomic force microscopy and scanning surface potential microscopy on patterned NO(2) aryl films are used to assess the molecular structure and orientation. A 100 mV decrease in the contact potential over NO(2) aryl films relative to bare ITO suggests that the aryl films are loosely structured as deposited with the NO(2) groups oriented at a small angle away from the ITO surface.

Performance following a sudden awakening from daytime nap induced by zaleplon.

BACKGROUND: Zaleplon appears to be a prime candidate for assisting individuals in obtaining sleep in situations not conducive to rest (i.e., a short period during the day). However, should an early unexpected awakening and return to duty be required, the effect on performance is not known. HYPOTHESIS: Zaleplon (10 mg) would negatively affect human performance for some duration, compared with placebo, after a sudden awakening from a short period (1 h) of daytime sleep. METHODS: There were 16 participants, 8 men and 8 women, who volunteered to participate in this study. The study was conducted using a counterbalanced, double-blind, repeated measures design. At 1 h prior to drug administration, and at each of 7 h postdrug, performance measures (cognition, memory, balance, and strength) and subjective symptom reports were recorded. RESULTS: Zaleplon had a statistically significant (p < 0.05) negative impact on balance through the first 2 h postdose when compared with placebo. In addition, symptoms related to "drowsiness" were statistically more prevalent under zaleplon than under placebo through the first 3 h postdrug. Of the eight measures of cognitive performance, six were significantly negatively impacted in the zaleplon condition through 2 h postdose when compared with placebo, with one remaining significantly degraded through 3 h postdose. Zaleplon also had a significantly negative impact on memory at 1 h and 4 h postdose. CONCLUSIONS: Zaleplon (10 mg), when used as a daytime sleep aid, causes drowsiness (and related symptoms) up to 3 h postdose, and may impact task performance, especially more complex tasks, for at least 2-3 h postdose.