Therapeutic potential of essential oil of Melaleuca quinquenervia (Myrtaceae) in a rat model of ethanol-induced peptic ulcer

Purpose: To evaluate the effects of M. quinquenervia extract on ethanol-induced peptic ulcer in rats. Methods: The following three groups of (n = 6) Sprague Dawley rats were included in this study: vehicle (C), ethanol-administered (E) and ethanol + M. quinquenervia-treated (MQ). MQ group rats received 100 μg/mL M. quinquenervia essential oil just before 96 % ethanol induction (1 ml/kg). One hour after ulcer induction, the animals were euthanized, and gastric and duodenal tissues were removed. Tissue samples were analysed for myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO) activity, malondialdehyde (MDA) and glutathione (GSH) levels, and histopathological examinations were performed by light microscopy. Results: Gastric and duodenal GSH levels that decreased in the ethanol-administered ulcer groups (p < 0.001), rose following MQ treatment (p < 0.5). Moreover, elevated MPO and MDA levels (p < 0.5) in gastric tissues decreased after MQ-treatment. Similarly, the MQ-treated group showed recovery and control-like morphology compared to the ethanol group in both gastric and duodenal tissues when examined by microscopy. Conclusion: The results indicate that M. quinquenervia extract has a positive impact on gastric injury in rats due to its antioxidant activity. Thus, the plant has a potential for the clinical management of gastric ulcer

Cold Therapy in Migraine Patients: Open-label, Non-controlled, Pilot Study

Some patients with headache report that they have frequently used physical therapies such as application of cold to relieve their headache. There are only a few reported studies related to cold therapies in patients with migraine. In this study, we investigated the effect of cold application on migraine patients. Twenty-eight migraine patients were included. Cold therapy was administered to them by gel cap. Patients used this cap during their two migraine attacks. Before and after the cold therapy, headache severity was recorded by using visual analogue scale (VAS). Patients used this cap for 25 min in each application. They recorded their VAS score just after the therapy and 25 min, 1 h, 2 h and 3 h later. Two patients could not use this therapy due to side effects (one due to cold intolerance and one due to vertigo) in both applications. Therefore, therapeutic efficacy was evaluated in 26 patients. Twenty-five minutes after treatment of the first attack, VAS score was decreased from 7.89 ± 1.93 to 5.54 ± 2.96 (P < 0.01). Twenty-five minutes after treatment of the second attack, VAS score was decreased from 7.7 ± 1.8 to 5.4 ± 3.55 (P < 0.01). Cold application alone may be effective in some patients suffering from migraine attacks. Its combination with conventional drugs should be investigated in future studies

In Vitro Investigations of miR-33a Expression in Estrogen Receptor-Targeting Therapies in Breast Cancer Cells

Background: Increased fatty acid synthesis leads to the aggressive phenotype of breast cancer and renders efficiency of therapeutics. Regulatory microRNAs (miRNAs) on lipid biosynthesis pathways as miR-33a have potential to clarify the exact mechanism. (2) Methods: We determined miR-33a expression levels following exposure of MCF-7 and MDA-MB-231 breast cancer cells to estrogen receptor (ER) activator (estradiol-17β, E2) or anti-estrogens (ICI 182,780, Fulvestrant, FUL) at non-cytotoxic concentrations. We related miR-33a expression levels in the cells to cellular lipid biosynthesis-related pathways through immunoblotting. (3) Results: miR-33a mimic treatment led to significantly downregulation of fatty acid synthase (FASN) in MCF-7 cells but not in MDA-MB-231 cells in the presence of estradiol-17β (E2) or Fulvestrant (FUL). In contrast to the miR-33a inhibitor effect, miR-33a mimic co-transfection with E2 or FUL led to diminished AMP-activated protein kinase α (AMPKα) activity in MCF-7 cells. E2 increases FASN levels in MDA-MB-231 cells regardless of miR-33a cellular levels. miR-33a inhibitor co-treatment suppressed E2-mediated AMPKα activity in MDA-MB-231 cells. (4) Conclusions: The cellular expression levels of miR-33a are critical to understanding differential responses which include cellular energy sensors such as AMPKα activation status in breast cancer cells

Advance Access Publication 15

Some patients with headache report that they have frequently used physical therapies such as application of cold to relieve their headache. There are only a few reported studies related to cold therapies in patients with migraine. In this study, we investigated the effect of cold application on migraine patients. Twenty-eight migraine patients were included. Cold therapy was administered to them by gel cap. Patients used this cap during their two migraine attacks. Before and after the cold therapy, headache severity was recorded by using visual analogue scale (VAS). Patients used this cap for 25 min in each application. They recorded their VAS score just after the therapy and 25 min, 1 h, 2 h and 3 h later. Two patients could not use this therapy due to side effects (one due to cold intolerance and one due to vertigo) in both applications. Therefore, therapeutic efficacy was evaluated in 26 patients. Twenty-five minutes after treatment of the first attack, VAS score was decreased from 7.89 ± 1.93 to 5.54 ± 2.96 (P &lt; 0.01). Twenty-five minutes after treatment of the second attack, VAS score was decreased from 7.7 ± 1.8 to 5.4 ± 3.55 (P &lt; 0.01). Cold application alone may be effective in some patients suffering from migraine attacks. Its combination with conventional drugs should be investigated in future studies. Keywords: cold application -cryotherapy -headache -migraine Introduction Migraine headache is generally treated by anti-migraine agents, analgesics and anti-emetic agents. Various nonpharmacological methods including massage, trigger point therapy, reflexology, spinal manipulation, therapeutic heat or cold and exercise therapy have also been investigated in the past for migraine patients (1-3). There are some reports which support the efficacy of acupuncture in the treatment of pediatric pain, including migraine (4). Ancient Greek and Egyptian writings show that physicians of that time were concerned about this disease and bloodletting and craniotomy was used in some patients with headache (2,5). The first cold treatment was done for headache patients in 1849. James Arnott wrote a manuscript on cold therapy in which he used a mixture of salt and ice in patients to treat headache (6). In another study, the efficacy of extra-cranial pressure in combination with cold to treat headaches was supported. They showed that simultaneous pressure of heat and cold reduced the headache&apos;s duration (7). Today, some patients report that they treat their headache using physical therapies, including cold application (5,8-10). Selfadministered pain relief manoeuvres have been investigated in primary headache patients. They reported that application of cold was the most-used manoeuvre in migraine without aura (8). In a small study, Friedman et al. (11) reported the efficacy of a non-invasive technique, intra-oral chilling, for acute migraine headache pain when compared with oral sumatriptan or placebo. Lance (12) reported the results of a new device, which employs cold, pressure and heat around the head. Fifteen out of twenty migraine patients and six out of seven tension headache patients experienced some reduction in headache severity. In another study, 9% of migraine patients reported that a cold wrap was almost completely effective, 26.5% moderately effective and 29.0% mildly effective. However, they did not use an objective method to evaluate headache severity (6). As a result, cold therapy is still not used clinically for migraine patients as an alternative or additive modality. In this study, we investigated the utility of cold therapy for migraine attacks. Materials and Methods All patients in this study were admitted to the Ministry of Health, Ankara Training and Research Hospital Headache Center. Informed consent was obtained from all patients. We obtained an Ethic Committee approval to conduct the study for patients (between 14 and 60 years) who met the criteria outlined below. Inclusion Criteria We proposed that all consecutively admitted patients, who met the following criteria, participate in our study: (i) migraine with aura and migraine without aura; (ii) chronic migraine [migraine headache occurring for 15 or more days per month for more than 3 months in the absence of medication overuse and not attributed to another disorder (other type chronic headache patients excluded)]; and that (iii) diagnosis was made by International Headache Society (IHS) criteria (13). The IHS determined new criteria for headache in 2004 Exclusion Criteria We excluded patients who had more than one type of headache (menstrual migraine was also excluded), took prophylactic treatment and patients with analgesic or ergotamine overuse. We reasoned that menstrual migraine may have different clinical characteristics and it can be more resistant than non-menstrual migraine. Patients using prophylactic treatment were deemed to be the possible cause of confusion when evaluating the responses of migraine patients. Twenty-eight migraine patients were included in this study. All patients were evaluated by a neurologist. Cap Administration All patients kept a diary for two migraine attacks (before and after the treatment). The diary included the time patients used the gel cap, visual analogue scale (VAS) of patients (before the treatment and 25 min, 1 h, 2 h, 3 h post-treatment), associated symptoms (i.e. nausea and vomiting) and side effects. Cold therapy was administered to the patients by gel cap In this study, we did not evaluate the patients beyond 3 h. This is a pilot study to determine the short-term effect of the treatment. Response Evaluation An objective response was defined as a 50% or greater reduction in pretreatment headache severity as measured by VAS. Patients with VAS score (0) were evaluated as having a complete response. A clinical benefit was defined as a reduction in VAS by &gt;25% in pretreatment headache severity. We thought that a 25% decrease in VAS score is an important level of clinical benefit. Therefore, we mentioned a 25% reduction in VAS as a clinical benefit. A patient whose VAS showed increase, no change or &lt;25% decrease was defined as no response. Statistical Analysis Bonferroni corrected Mann-Whitney U-test and Paired Samples t-test were used for statistical analysis. P-values &lt;0.05 were accepted as significant. Results All patients were female and the median age was 29.25 ± 7.92 years (range: minimum 14; maximum 48). Twenty-six patients had migraine without aura and two patients had migraine with aura. The patients&apos; mean number of attacks per month was 3.11 ± 1.2 (minimum 1; maximum 5). Characteristics of patients are shown in 490 Cold therapy in migraine patients Half of the Patients Reported a Clinical Benefit In the first application, 13 patients (50%) reported a clinical benefit 25 min after the cold therapy. Objective response was observed in 10 (38.4%) patients including three (11.5%) patients who had a complete response. However, the other half did not respond and needed to use analgesics 25 min after cold therapy. Mean VAS scores of patients decreased from 7.89 ± 1.93 to 5.54 ± 2.96 in 25 min, 4.62 ± 3.16 in 1 h, 3.92 ± 3.32 in 2 h and 3.42 ± 3.55 in 3 h after cold therapy in first attack. VAS scores at the twenty-fifth minute, first hour, second hour and third hour of treatment were found to be significantly lower compared to VAS scores before treatment (P &lt; 0.01) Benefit Increased with Second Application In the second application, 15 (57.6%) patients reported a clinical benefit 25 min after the cold therapy. Objective response was observed in 9 (34.6%) patients including 2 (7.7%) patients who had a complete response, but 11 (42.4%) did not respond and used analgesics. Mean VAS scores decreased from 7.74 ± 1.81 to 5.40 ± 3.10 in 25 min, 4.76 ± 3.88 in 1 h, 4.60 ± 3.75 in 2 h and 4.04 ± 3.54 in 3 h. VAS scores at the twenty-fifth minute, first hour, second hour and third hour of treatment were found to be significantly lower compared to VAS scores before the treatment (P &lt; 0.01) Median Analgesic Intake Time Increased with the Second Application Median analgesic intake time after onset of cold therapy was 45.0 ± 35.7 min (range: 25-120 min) in the first application and 81.36 ± 118.4 (range: 25-420 min) min in the second. Discussion Migraine is a chronic disease characterized by frequent attacks, high levels of pain and disability during attacks, causing reduced quality of life between attacks (15-18). It is a widespread disorder in the world, affecting $10-15$50% of the patients by cold therapy alone, with significantly decreased VAS scores after the therapy. In addition, we found that the benefit of cold therapy continued progressively over time. VAS scores gradually decreased after the therapy. This shows that the benefits of cold therapy continued after the onset of therapy. Moreover, there was consistency in the cold applications. Seventy-six percent of patients who had a response in their first attack benefited from the cold therapy in the second attack. Similarly, 60% of the patients who did not respond in the first attack had no response in the second attack, either. This study is not a randomized study and there is no control group comparing usual therapeutic approaches such as anti-migraine agents and anti-emetics. Therefore, we cannot conclude that cold therapy is definitely effective in migraine attack and we cannot suggest an evidence-based use of cold therapy in migraine patients. We can say, however, that cold therapy alone warrants investigation in future randomized control studies. In pharmacological trials on migraine drugs, rescue medications are usually allowed after 2 h. In our study, we allowed our patients to take analgesics 25 min after the therapy onset. However, median analgesics intake time after onset of cold therapy was 45.0 min in the first and 81.36 min in the second attack of patients who did not respond to gel cap therapy. In the present study, 13 patients in first application and 11 in second application used analgesic drugs due to inefficacy of cold therapy alone. As seen in The placebo effect in the pharmacological treatment of migraine attacks may influence evaluation of the studies. In a meta-analysis of 31 trials involving acute migraine patients, it has been reported that the mean proportion of subjects who experienced a treatment response to placebo was 28% (24). In our study, the response rate was 50% in the first attack and 57% in the second attack. Moreover, placebo effect may vary in each patient and each attack. Therefore, our results cannot be completely attributed to placebo effect of gel therapy. However, we cannot ignore its possible effect on our results. If we accept the cold treatment as an effective modality in migraine patients, there is still one more question to be resolved: How does cold affect the migraine headache? Local anesthesia is important in the use of cryotherapy. Lowering pain stimuli may be caused by a decrease in contraction. The gate theory suggests that the cold sensations overwhelm and block transmission of the pain stimuli into the cerebral cortex. Ice reduces the release of some substances including histamines, vasoactive substances and enzymes that stimulate nerve endings (6). However, the exact mechanism of cryotherapy is still unclear. In Vijayan&apos;s (1) study, two patients could not apply adequate pressure in cold therapy because of tenderness. In our study three patients showed side effects in both applications. Two patients had cold intolerance and one had vertigo. Two of them discontinued the therapy. The use of gel packs is a safe method of applying cold in adjunct treatment of acute headache

Antibodies Against EGF-Like Domains in \u3ci\u3eIxodes scapularis\u3c/i\u3e BM86 Orthologs Impact Tick Feeding and Survival of \u3ci\u3eBorrelia burgdorferi\u3c/i\u3e

Ixodes scapularis ticks transmit multiple pathogens, including Borrelia burgdorferi sensu stricto, and encode many proteins harboring epidermal growth factor (EGF)-like domains. We show that I. scapularis produces multiple orthologs for Bm86, a widely studied tick gut protein considered as a target of an anti-tick vaccine, herein termed as Is86. We show that Is86 antigens feature at least three identifiable regions harboring EGF-like domains (termed as EGF-1, EGF-2, and EGF-3) and are differentially upregulated during B. burgdorferi infection. Although the RNA interference-mediated knockdown of Is86 genes did not show any influences on tick engorgement or B. burgdorferi sensu stricto persistence, the immunization of murine hosts with specific recombinant EGF antigens marginally reduced spirochete loads in the skin, in addition to affecting tick blood meal engorgement and molting. However, given the borderline impact of EGF immunization on tick engorgement and pathogen survival in the vector, it is unlikely that these antigens, at least in their current forms, could be developed as potential vaccines. Further investigations of the biological significance of Is86 (and other tick antigens) would enrich our knowledge of the intricate biology of ticks, including their interactions with resident pathogens, and contribute to the development of anti-tick measures to combat tick-borne illnesses

The effects of financialisation and financial development on investment: Evidence from firm-level data in Europe

In this paper we estimate the effects of financialization on physical investment in selected western European countries using panel data based on the balance-sheets of publicly listed non-financial companies (NFCs) supplied by Worldscope for the period 1995-2015. We find robust evidence of an adverse effect of both financial payments (interests and dividends) and financial incomes on investment in fixed assets by the NFCs. This finding is robust for both the pool of all Western European firms and single country estimations. The negative impacts of financial incomes are non-linear with respect to the companies’ size: financial incomes crowd-out investment in large companies, and have a positive effect on the investment of only small, relatively more credit-constrained companies. Moreover, we find that a higher degree of financial development is associated with a stronger negative effect of financial incomes on companies’ investment. This finding challenges the common wisdom on ‘finance-growth nexus’. Our findings support the ‘financialization thesis’ that the increasing orientation of the non-financial sector towards financial activities is ultimately leading to lower physical investment, hence to stagnant or fragile growth, as well as long term stagnation in productivity

Impact on refractive surgery due to increasing use of personal protection equipment: Insights from EUROCOVCAT group

Since the World Health Organization declared COVID-19 to be a pandemic on 11th March 2020, changes to social and sanitary practices have included significant issues in access and management of eye care during the COVID-19 pandemic. Additionally, the fear of loss, coupled with social distancing, lockdown, economic instability, and uncertainty, have led to a significant psychosocial impact that will have to be addressed. In the current COVID-19 pandemic, personal protective equipment such as face masks or face coverings have become a daily necessity. While "mass masking" along with hand hygiene and social distancing became more widespread, new issues began to emerge - particularly in those who wore spectacles as a means of vision correction. As we began to see routine patients again after the first lockdown had been lifted, many patients visited our clinics for refractive surgery consultations with a primary motivating factor of wanting spectacle independence due to the fogging of their spectacles as a result of wearing a mask. In this article, we report on new emerging issues in eye care due to the widespread use of masks and on the new unmet need in the corneal and cataract refractive surgery fields

Carbamazepine overdose after exposure to simethicone: a case report

<p>Abstract</p> <p>Introduction</p> <p>Carbamazepine is an anticonvulsant drug and is also used as a treatment for patients with manic-depressive illness, post-herpetic neuralgia or phantom limb pain. The drug itself has many drug interactions. Simethicone is an antifoaming agent and is reported to be an inert material with no known drug interaction with carbamazepine.</p> <p>Case presentation</p> <p>We present a case of a patient who was routinely using carbamazepine 400 mg three times per day and levetiracetam 500 mg twice daily, and experienced carbamazepine overdose after exposure to simethicone. After cessation of simethicone therapy normal drug levels of carbamazepine were obtained again with the standard dose of the drug. The mechanism of interaction is unknown but the risk of overdose should be considered when prescribing simethicone to a patient who is using carbamazepine.</p> <p>Conclusion</p> <p>Simethicone and carbamazepine, when taken together, may be a cause of carbamazepine toxicity. The risk of carbamazepine overdose should be considered when prescribing simethicone to a patient who is using carbamazepine.</p

Composite structural motifs of binding sites for delineating biological functions of proteins

Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs which represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures.Comment: 34 pages, 7 figure

The bouba/kiki effect is robust across cultures and writing systems

The bouba/kiki effect-the association of the nonce word bouba with a round shape and kiki with a spiky shape-is a type of correspondence between speech sounds and visual properties with potentially deep implications for the evolution of spoken language. However, there is debate over the robustness of the effect across cultures and the influence of orthography. We report an online experiment that tested the bouba/kiki effect across speakers of 25 languages representing nine language families and 10 writing systems. Overall, we found strong evidence for the effect across languages, with bouba eliciting more congruent responses than kiki. Participants who spoke languages with Roman scripts were only marginally more likely to show the effect, and analysis of the orthographic shape of the words in different scripts showed that the effect was no stronger for scripts that use rounder forms for bouba and spikier forms for kiki. These results confirm that the bouba/kiki phenomenon is rooted in crossmodal correspondence between aspects of the voice and visual shape, largely independent of orthography. They provide the strongest demonstration to date that the bouba/kiki effect is robust across cultures and writing systems. This article is part of the theme issue 'Voice modulation: from origin and mechanism to social impact (Part II)'.Peer reviewe